Search results for “inflammatory”

Activation of Transcription Factor EB Protects Against Proinflammatory Insults Through NF-κB Inhibition in Keratinocytes

Keratinocytes are pivotal in mediating cutaneous inflammation. Identifying anti-inflammatory factors within these cells holds promise for developing novel therapeutic strategies to manage skin inflammation. Transcription factor EB (TFEB) has recently emerged as a key regulator linking cellular energy metabolism to inflammatory processes, primarily through its influence on autophagy and NF-κB signaling. However, whether TFEB activation exerts anti-inflammatory effects in keratinocytes remains unclear. In vitro inflammation model was established in HaCat cells by incubation with proinflammatory mediators LPS and IL-1β. Cell viability and TFEB expression and phosphorylation were measured. The effect of TFEB activation by C1 and adenoviral TFEB overexpression on the expression of proinflammatory genes including COX-2, MCP-1 and IL-6 were detected. Also, IκBα protein level were determined. TFEB phosphorylation is increased while TFEB total protein expression is inhibited by treatment with LPS and IL-1β. Pharmacological activation of TFEB by compound C1 and TFEB overexpression suppressed the expression of COX-2, MCP-1 and TNF-α induced by LPS and IL-1β. TFEB overexpression increased basal IκBα expression and restored IκBα level under LPS treatment. TFEB knockdown reduced TFEB expression and lowered basal expression level of COX-2, MCP-1 and TNF-α. Our findings indicate that TFEB activation can mitigate inflammatory gene expression in keratinocytes triggered by LPS and IL-1β. This implicates TFEB as a significant novel modulator of cutaneous inflammation, highlighting its potential as a therapeutic target. Targeting TFEB could thus be a viable strategy for developing new treatments for chronic inflammatory skin conditions.

Study of Anti-Inflammatory Effects of Black Cumin (Nigella Sativa) and Honey on Mice (Mus Musculus)

The study was conducted to determine the effect of Nigella sativa (Kalonji) and Honey as an anti-inflammatory agent for humans and animals. The study was carried out on 20 Albino Mice of almost equal size and weight. All the mice were given 5% solution of formalin in a dose of 0.5ml injection in their right hind paw to produce artificial inflammation. The mice were divided into four groups of five animals in each and were randomly allotted to four treatments as Group A (Control) where no Nigella sativa extract and honey were given, Group B where the mice were given only the ethanolic extract of Nigella sativa in the dose of 0.05ml injection as a remedy of inflammation, Group C where the mice were given only the honey orally in a dose of 0.05mg and Group D where mice were given 50% (0.025ml) intraperitoneally of Nigella sativaextract and 50% (0.75mg) of honey as an anti-inflammatory agents. The data was statistically analyzed by the Analysis of Variance (ANOVA) and the results showed that the inflammation was significantly (p<0.05) reduced in mice given treatments compared to untreated control group and among treated groups. The mice given the extract of Nigella sativa (Group B) showed better results (p<0.05) in reducing the inflammation compared to other groups (C and D), Group D where the mice were given 50% (0.025ml) Nigella sativa extract and 50% (0.75mg) honey showed better results (p<0.05) than mice given only honey. Overall, both the extract of Nigellasativa and the honey were almost equally successful in reducing the inflammation in mice which showed that these two agents can successfully be used as anti-inflammatory drugs in humans and animals.

Evaluation of Inflammatory Serum Cytokines after Treatment with the Consciousness Energy Healing Based Proprietary Test Formulation on Combination of Cecal Slurry, LPS and E. Coli Induced Systemic Inflammatory Response Syndrome (SIRS) in Sprague Dawley Rats

Sepsis is a systemic inflammatory response to a confirmed or suspected infection. The transition from sepsis to septic shock causes high rate of mortality. The aim of this experiment was to evaluate the anti-inflammatory potential of the Biofield Energy Treated (Blessed) Proprietary Test Formulation and Biofield Energy Healing (Blessing) Treatment per se to Sprague Dawley rats on Cecal Slurry, LPS, and E. coli-induced systemic inflammatory response syndrome (SIRS) model. In this experiment, various proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, IL-12, 1L-17, and interferon-γ (IFN-γ) were analysed using ELISA. A test formulation was formulated including minerals (magnesium, zinc, calcium, selenium, and iron), vitamins (ascorbic acid, pyridoxine HCl, vitamin E, cyanocobalamin, and cholecalciferol), Panax ginseng extract, β-carotene, and cannabidiol isolate. The constituents of the test formulation were divided into two parts; one section was defined as the untreated test formulation, while the other portion of the test formulation and three group of animals received Biofield Energy Healing Treatment remotely for about 3 minutes by a renowned Biofield Energy Healer Mr. Mahendra Kumar Trivedi. The level of TNF-α was significantly reduced by 40.50%, 85.36% (p≤0.01), 50.66% (p≤0.01), 87.38% (p≤0.01), and 58.63% (p≤0.01) in G5 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treated test formulation), G6 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treatment per se to animals from day -15), G7 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treated test formulation from day -15), G8 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treatment per se + Biofield Energy Treated test formulation from day -15), and G9 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treatment per se animals + untreated test formulation) groups, respectively as compared to the disease control (G2) group. Additionally, the level of IL-1β was decreased by 17.04%, 15.56%, and 12.59% in G6, G8, and G9 groups, respectively as compared to the untreated test formulation (G4) group. The level of IL-6 was significantly (p≤0.001) reduced by 36.18%, 50.24%, 43.25%, 52.69%, and 38.23% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. The level of IL-10 was altered by 70.53%, 49.25%, 60.18%, 41.54%, and 58.89% in G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. Moreover, the level of IL-12 was decreased by 30.24%, 31.67%, 29.82%, 45.77%, and 50.54% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2. The level of IL-17 was reduced by 48.75%, 59.61%, 59.28%, 62.49%, and 58.65% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2. IFN-γ expression was reduced by 49.56%, 24.09%, 23.7%, 56.98%, and 44.94% in G5, G6, G7, G8, and G9 groups, respectively than G2. Overall, the data suggested anti-inflammatory potentials of the Biofield Energy Treated test formulation and Biofield Energy Treatment per se along with preventive measure on the animal with respect to various inflammatory conditions that might be beneficial various types of systemic inflammatory disorders specially sepsis, trauma, septic shock or any types of injuries. Therefore, the results showed the significant slowdown the inflammation-related disease progression and its complications in preventive treatment groups viz. G6, G7, G8, and G9.

Antioxidant and Anti-Inflammatory Activities of Biofield Energy Treated Proprietary Test Formulation in Brain Tissues in Cecal Slurry, LPS and E. Coli-Induced Systemic Inflammatory Response Syndrome (SIRS) in Sprague Dawley Rats

Evaluation of Vitamin D3 metabolite (25-OH Vit D3), Neurotransmitter (ACh), and the Expression of Proinflammatory Cytokines (IL-6 and TNF-α) in Tissue Homogenate after Administration of Biofield Energy Healing-based Novel Proprietary Test Formulation and Biofield Treatment per se to the Animals in Vitamin D3 Deficiency Diet (VDD)-induced Sprague Dawley Rats

A novel proprietary test formulation was designed which included minerals, vitamins, β-carotene, cannabidiol isolate,and Panax ginseng extract. This present study was evaluated the impact of the Trivedi Effect® on novel proprietary test formulation in male Sprague Dawley rats, fed with vitamin D3 deficiency diet (VDD). The novel test formulation was divided into two parts; one part was defined as untreated test formulation, while the other part was defined as the Biofield Energy Treated sample, which received the Biofield Energy Healing Treatment by renowned Biofield Energy Healer, Mr. Mahendra Kumar Trivedi. The level of 25-OH Vit. D3 was measured in brain homogenate, which was found to be increased by 20.13%, 24.12%, 45.86%, 14.79%, and 29.96% in the G5 group treated with Biofield Treated test formulation, Biofield Energy Treatment per se to the animals (G6), 15 days pre-treatment of Biofield Energy Treated test formulation (G7), Biofield Energy Treatment per se plus Biofield Energy Treated test formulation from day -15 (G8), and untreated test formulation to the Biofield Energy Treated animals (G9) groups respectively, as compared with the disease control (G2) group. Brain acetylcholine (ACh) level was increased by 61.33% in the G7 group as compared with the untreated test formulation (G4) group. The expression of interleukin-6 (IL-6) was significantly reduced by 43.44% (p≤0.01), 30.93%, 21.42%, 45.99% (p≤0.01), and 60.85% (p≤0.01), respectively as compared with the G4. Lung pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) level was significantly reduced in the G5, G6, G7, and G8 by 24.86%, 32.55% (p≤0.01), 30.12% (p≤0.01), and 42.69% (p≤0.01), respectively, as compared with the G4 group. Altogether, the Biofield Treated test formulation and/or per se treatment to the animals significantly improved the levels of active form of vitamin D3 metabolite (25-OH Vit D3) and neurotransmitter (ACh); consequently significantly lowered the expression of proinflammatory cytokines (IL-6 and TNF-α). Therefore, the energized test formulation or per se treatment could be effectively useful against neuronal damage and inflammation for the management of brain disorders such as Alzheimer’s disease, dementias, brain cancer, epilepsy and other seizure disorders, mental disorders, and Parkinson’s. Thus, the results showed a significant slowdown of disease progression and all other disease-related complications/symptoms in the preventive Biofield Energy Treatment group per se and the Biofield Energy Treated Test formulation groups (viz. G6, G7, G8, and G9) as compared to the disease control group.

Resveratrol Prevents Cataract Formation by Inhibiting Pro-inflammatory Mediator-induced Dysregulation of Lens Calcium

The effect of resveratrol, a free radical scavenger, during cataract development was evaluated in the Wistar rat pup model. This study investigated the possible free radical scavenging potential of resveratrol at 40 mg/ kg body wt dose in selenite-induced cataract in rat pups. Intraperitoneal injection of sodium selenite (15 µm mol/ kg body wt) in 8 to 10 day old rat pups lead to severe oxidative stress in the tissues evidenced by decreased antioxidants and increased lipid peroxidase, nitric oxide, superoxide anion, hydroxyl radical generation, inducible nitric oxide synthase (iNOS) as well as nuclear factor kappa B (NF-kB) expression levels that probably led to cataract formation. Selenite exposure also caused an increase in total calcium in the eye lens and significantly inhibited the activity of Ca2+ ATPase but not Na+/ K+ ATPase or Mg2+ ATPase. However, both pre- and co-treatments with resveratrol, but not post-treatment, led to an increase in antioxidant levels with a concomitant reduction in oxidative stress and also rescued the selenite-mediated increase in lens Ca2+ and inhibition of Ca2+ ATPase activity in the eye lens. The results of this study demonstrate antioxidants decrease and increase in free radical generation triggered by selenite causes the inactivation of lens Ca2+ ATPase leading to a rise in intracellular Ca2+ level. Resveratol treatment was able to prevent selenite-induced oxidative stress and in turn the inhibition of lens opacification. Thus, resveratrol has the potential to function as an anti-cataractogenic agent, possibly by preventing free radical-mediated accumulation of Ca2+ in the eye lens.

Evaluation of the Relationship Between Advanced Oxidation end Products and Inflammatory Markers in Maintenance Hemodialysis Patients

Introduction Increased oxidative stress and blunted anti-oxidant mechanisms are important problems in hemodialysis (HD) patients. Reactive oxygen species (ROS) act directly on proteins, leading to the formation of oxidized amino acids. Advanced oxidation protein products (AOPP) are among these substances. Many oxidant substances increase the level of AOPP. Iron is an element with strong oxidant capacity, especially when used intravenously. It is thought that iron treatment further increases the oxidative stress in HD patients. We aimed to investigate the relationship between AOPP and inflammatory status in HD patients. Materials and Methods Patients who were on maintenance HD program without additional co-morbidities and no history of use of intravenous iron within the last two weeks were recruited in the study. The blood samples taken just before the dialysis session were analyzed for AOPP, serum iron, total iron binding capacity (TIBC), ferritin, C-reactive protein (CRP), ß2-microglobulin, fibrinogen, interleukin (IL)-1, IL-6 and tumor necrosis factor-α levels besides routine biochemical measurements and complete blood count. Results The number of patients included in the study was 102 (n: 53 female, %52.0) and the mean age was 47.6±13.9 years. The mean transferrin saturation was 25.4%. AOPP levels, iron use in patients was higher compared to patients who do not use (respectively 2.58±0.19 mmol/l and 2.50 ±0.16mmol/l, p = 0.046). We did not detect statistically significant correlation of AOPP levels with iron parameters and other inflammatory markers. Conclusion The present study showed that intravenous iron therapy does not increase oxidative stress. Although serum AOPP level was higher in patients on intravenous iron treatment, it was not correlated with iron indices and inflammatory markers. So, intravenous iron may exert its oxidant effect free from serum iron indices.

Cardiac Inflammatory Pseudotumors in Behçet’s Disease

Introduction Cardiac non-specific inflammatory pseudotumors (NSIPT) are exceptionally associated to Behçet's disease (BD) and represent a real diagnostic and therapeutic challenge. The meaning and the mechanisms of this association are not yet well understood. The purpose of this paper is to study the epidemiologic, therapeutic, and evolutionary characteristics of cardiac NSIPT during BD Methods Systemic review of all reported cases of cardiac NSIPT associated with BD. Results We found only 6 cases of NSIPT associated with BD. Of these six patients, 4 were men (66.66%) and 2 were women (33.33%): Sex ratio =2. The average age was 26.66 years (9-35 years). The pseudotumor was unique in all cases. The chronology of occurrence of these NSIPT compared to the underlying angiitis was variable: inaugural of the disease in 4 cases, and complicating a previously known BD in 2 cases. The surgery was performed in all cases. It was carried out for diagnostic purpose in 4 cases, and therapeutic in the other 2. Additional medical treatment based on systemic corticosteroids with or without immunosuppressants was indicated in 4 patients. The evolution was favorable in 5 cases and a single case was quickly fatal. Recurrence of NSIPT was reported in one patient (20%). Conclusion The results of this review suggest a very likely association between BD and cardiac NSIPT; especially because of the scarcity of these two conditions in the general population, and the epidemiological characteristics clearly different from those of cardiac NSIPTs in the general population. The pathogenic mechanisms common to these two conditions (immune, inflammatory, reactive, and vascular) reinforce this causal link. The main differential diagnoses of these pseudotumors during BD remain cancer and intracardiac thrombosis.

Developing Cellular & Molecular Biomarkers for Anti-Inflammatory Activities of Probiotic Bacteria in Fermented Foods

We present below a mechanistic cellular and molecular approaches for the development of Anti-Inflammatory biomarkersof Probiotic Bacteria in Fermented Foods. Probiotics are live microorganisms that promote human health by counteracting the noxious toxic gut microflora in human intestine, by modulating of the tight junctions, and by increasing mucin production, enforcing intestinal epithelial cell barrier function, modifying microbial community within the gut intestinal disorders, and improving immune responses associated with chronic inflammation in experimental animal models, collectively enhancing human health. Cytokine secretion by intestinal epithelial cells and macrophages are regulated by probiotics through key signaling pathways such as nuclear factor-κB and mitogen-activated kinases, resulting in alleviation of several disorders such as allergies, diabetes, obesity, heart diseases and cancer. MicroRNAs are small non-coding RNA molecules involved in transcriptional and post-translational regulation of gene expression by inhibiting gene translation. Using in vitro and in vivo approaches in cell lines and mice models to study effects of probiotic conditional media and heat-killed bacterial strains with anti-inflammatory effect to elucidate the mechanisms by which probiotics affect signaling pathways, and by using global cytokine and microRNA gene expression analyses approaches to develop biomarkers for studying different pro- and anti-inflammatory activities, and using statistical approaches to analyse the data, we show that cytokines and miRNAs have an essential role in regulation of cancerous and inflammatory pathways. This mechanistic approach will result in developing specific disease biomarkers for the early diagnosis of certain pathogenic states, as well as evaluating the effect of different dietary components on developed biomarkers in health states that will promote and enhance human health. Comparing the concordance of the in vitro to the in vivo research findings will confirm the correspondence of both approaches to each other. Moreover, this study will have a major public health relevance in elucidating the role of miRNAs and their targets in inflammation, paving the way to diagnosing and treating of pathogenic human disease stages.

Profile of Similarity of Electron Withdrawing Structure Towards Analgesic-Anti-Inflammatory Activity of The Novel Isatin Analogue: Design and Implementation of Phase I Drug Discovery

Isatin (1H-indole-2,3-dione ) and derivatives demonstrate a diverse array of biological activities. Isatin and 5-halo derivatives has reacted to form the schiff’s bases , mannich bases and friedal craft alkylation’s to form C-C, C-N, C=N bonds. From the spectral studies, isatin has undergoes reaction at C-3 and N-1 position and synthesized lead in present schme and seen the similarity of structure and analgesic-anti-inflammatory activity.

Association of Gestational Diabetes and Proinflammatory Cytokines (IL-6, TNF-α and IL-1β)

Changes to proinflammatory cytokines as a result of gestational diabetes mellitus (GDM), and the pregnancy complications that these changes can cause, are of vital importance to the effective prevention and optimal management. Interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) are cytokines that are associated with gestational diabetes. Therefore, the aim of this review is to draw attention to the relationship between gestational diabetes and these diseases

Novel N-Pyrrolylcarboxylic Acid Derivative as a Potential New Analgesic and Anti-Inflammatory Drug

The objective of our study was to evaluate the analgesic and anti-inflammatory activity, as well as possible organ toxicity of 2-3-3-methyl-pentanoic acid (compound 3d), a newly synthesized pyrrolic derivative, structurally similar to Celecoxib. Antinociception was assessed using animal pain models with thermal and chemical stimuli (paw withdrawal, tail-flick and formalin test). Anti-inflammatory activity was measured using the carrageenan-induced paw edema model. Blood samples were collected from the animals to study possible organ toxicity. All experiments were performed on male Wistar rats. The results in our study show that in experimental conditions 2-3-3-methyl-pentanoic acid has analgesic action against thermal and chemical stimuli. This effect is registered after both single and multiple administration of the compound. In the carrageenan model after single administration compound 3d did not inhibit formation of paw edema. After multiple administration all doses of compound 3d significantly suppressed paw edema at second, third and fourth hours. Hematological tests showed that compound 3d did not affect red blood cells and platelets but decreased white blood cell levels and the highest used dose decreased hemoglobin as well. Compound 3d decreased blood sugar levels and liver transaminases, compared to the control. Compound 3d did not affect creatinine levels but the smallest dose used lowered blood urea. We concluded antinociception in the tested compound is most likely mediated by supraspinal, spinal and peripheral mechanisms. Possible tolerance develops towards the analgesic action on spinal level after continuous administration. Anti-inflammatory activity, though significant, is probably not the leading cause for antinociception.

Relationship Between Inflammatory Infiltrate Canine Mammary Carcinomas.

The mammary tumor is one of the most common cancer in female dogs and, at the present days, there is a big focus on the study of the relation between this kind of tumor in animals and the cells that stay around them, like the inflammatory cells. The objective of this study was to evaluate and show where the inflammatory cells stay in simple mammary carcinomas in female dogs by immunohistochemistry. Samples of simple mammary carcinomas (tumor group; n=26) and mammary gland samples without tumor (control group; n=18) were submitted to immunohistochemical analysis for the detection of T lymphocytes, macrophages, plasma cells and the MHC-II molecule. The mast cells were evaluated by the histochemical technique (toluidine blue). Lymphocytes, macrophages and mast cells were observed distributed in the tumor stroma. MHC-II was detected in tumor cells and in the inflammatory infiltrate. Plasma cells predominated in the peritumoral stroma. Macrophages differed significantly between the two groups and predominated in the tumor group. In the comparison between histological types of mammary carcinomas, mast cells differed significantly between solid tumors of the tubular / papillary types. The cytoplasmic immunodetection of MHC-II was suggested an inefficient antigen presentation. Some of the leukocytes present in the tumor infiltrate, appear to be exerting a pro-tumor effect and allowing the progression of tubular and papillary carcinomas. But in solid carcinomas (may be poorly immunogenic), as they had the lowest proportion of leukocytes present in the tumor site. More studies are necessary to confirm these results, such as the determination of the cytokine profile and the predominant leukocyte subpopulations in the tumor microenvironment.

Docosahexaenoic Acid Supplementation is Not Anti- Inflammatory in Adipose Tissue of Healthy Obese Postmenopausal Women

Adipose tissue inflammation is associated with obesity comorbidities. Reducing such inflammation may ameliorate these comorbidities. n-3 fatty acids have been reported to have anti-inflammatory properties in obesity, which may modulate this inflammatory state. In the current study a 1 gram per day oral supplement of the n-3 fatty acid docosahexaenoic acid (DHA) was administered for 12 weeks to 10 grade 12 obese postmenopausal women and markers of adipose tissue and systemic inflammation measured and compared before and after supplementation. DHA administration resulted in approximately a doubling of plasma and red cell phospholipid and adipose tissue DHA content but no change in systemic markers of inflammation, such as circulating C-reactive protein (CRP) or interleukins (IL) 6, 8 and 10 (IL-6, IL-8, IL-10). DHA supplementation did not alter the adipose tissue marker of inflammation crown-like structure density nor did it affect any gene expression pathways, including anti-inflammatory, hypoxic and lipid metabolism pathways. The obese postmenopausal women studied were otherwise healthy, which leads us to suggest that in such women DHA supplementation is not an effective means for reducing adipose tissue or systemic inflammation. Further testing is warranted to determine if n-3 fatty acids may ameliorate inflammation in other, perhaps less healthy, populations of obese individuals.

Psychological “Risks” of Colonoscopy are Greater Amongst Fecal Immunohistochemical Test Positive Individuals than those with Inflammatory Bowel Disease

Background: Colorectal cancer (CRC) screening by Fecal Immunohistochemical Testing (FIT) followed by colonoscopy reduces colorectal cancer mortality. Barriers to colonoscopy should be minimised. Objective: To compare psychological “risks” of colonoscopy in FIT positive (FIT+) subjects and those with Inflammatory Bowel Disease (IBD). Method: IBD patients undergoing colonoscopic CRC surveillance were age and gender matched with FIT+ individuals awaiting colonoscopy. Subjects completed Spielberger State and Trait Scales for current levels of anxiety, depression, anger and curiosity, versus long term personality tendencies. Results: 70 IBD respondents were matched with 70 FIT+ respondents, (57% male, mean age 57.6 years). FIT+ subjects demonstrated greater scores for state Anxiety (22.3 vs 20.3 p=0.024), Curiosity (24.3 vs 21.8 p=0.036), Anger (13.7 vs11.5 p=0.037) and Depression (23.8 vs21.2 p=0.002). Conclusion: FIT+ patients experience more anxiety and depression prior to their colonoscopy than IBD patients, which may reduce colonoscopy uptake and is important to address.

Current Status of Nonsteroidal Anti-Inflammatory Drugs in Colorectal Cancer Prevention

This review synthesizes evidence on NSAIDs and colorectal cancer prevention. It balances chemopreventive efficacy against gastrointestinal and cardiovascular risks, and considers selective COX‑2 inhibitors, dosing, and candidate populations for risk‑benefit.

High-Throughput Complex Disease Modeling for Ethical Drug Discovery: Clinical Relevance of a NAM Platform for Cancer Biomarker Development

The development of tumor biomarkers derived from blood, or its components, has become pivotal in advancing early cancer diagnosis. Malignant transformations induce cancer-specific alterations in the transcriptome, proteome, and secretome of tumor cells. Recent studies highlighted similar alterations in peripheral blood mononuclear cells (PBMCs) in cancer patients, which appear to mirror the state of transformation in tumor cells. These findings suggest an intercellular communication–driven mechanism rather than a systemic inflammatory response and, in addition to current ctDNA-based liquid biopsy biomarkers, point to a novel, simple, and highly robust approach for the early detection of cancer. Using this phenomenon to advance PBMC-based biomarker development, it will be essential to achieve 3D in vitro tumor models that reproduce a highly physiological tumor microenvironment (TME). Likewise, more enhanced 3D ex vivo models are required to enable the replication of cell-to-cell and organ-to-organ communication. These systems will guide the self-organization of mixed microenvironments derived from different tissues and enable them to accurately reproduce the molecular connections underlying these alterations. In this study, an innovative new modular 3D co-culturing approach was used to expose PBMCs to lung tumoroids, under physiologically relevant conditions. Changes in DNA fragmentation of PBMCs in the presence of lung cancer were quantified and used as a biomarker. To validate the predictiveness of this biomarker, our results were compared with clinical data from a clinical evaluation study. Similar to the clinical trial observations, PBMCs, when exposed to lung tumoroids, showed a significantly lower level of DNA fragmentation (37%). This modular 3D co-culturing model showed a predictiveness of the clinical data of > 90%, demonstrating its power to monitoring cell-to-cell communication effects and support the development of blood-based biomarkers.

Diabetic Mouse Delayed Wound Model Following Treatment with the NerveStim™ Neuropathy System

Delayed wound healing in diabetes is characterized by impaired angiogenesis, persistent inflammation, extracellular matrix dysregulation, and peripheral neuropathy. A preclinical study was conducted using a diabetic mouse delayed wound model to evaluate the surrounding tissue of a wound, (its periwound) and its tissue responses following treatment with the NerveStim™ Neuropathy System, a combination topical gel and neuromuscular electrical stimulation platform. Periwound tissue was harvested at Day 14 and analyzed using NanoString gene expression profiling. Treated animals demonstrated visibly increased periwound tissue thickness compared to untreated controls. Differential expression analysis identified 76 significantly upregulated and 17 downregulated genes. Upregulated pathways included angiogenesis (Vegfa, Fgf2, Pdgfb, Nos3), neurotrophic signaling (Ngf, Bdnf, Scn9a, Trpv1), macrophage polarization (Arg1, Mrc1, Il10), and extracellular matrix remodeling (Col1a1, Col3a1, Mmp9, Timp1). Downregulation of select pro-inflammatory mediators (Nos2, Mif) was observed. These coordinated transcriptional changes are consistent with activation of reparative immune, neurovascular, and matrix remodeling pathways in diabetic periwound tissue.

Lineage-Specific Disruption of Hematopoiesis by Oxaliplatin: Mechanisms of Erythropoietin Resistance and Immune Suppression

Background Oxaliplatin, a widely used chemotherapeutic agent, is associated with hematologic toxicities such as anemia, leukopenia, and thrombocytopenia. Despite their clinical relevance, the molecular mechanisms underlying lineage-specific bone marrow suppression remain poorly understood. Methods We administered oxaliplatin to mice over eight weeks and performed RNA-sequencing (RNA integrity >8) on bone marrow alongside peripheral blood analysis and cytokine profiling. Transcriptomic data were analyzed to identify differentially expressed genes (DEGs) and enriched pathways. For that, we applied a thematic Gene Ontology (thematicGO) enrichment method that groups GO terms into biologically meaningful categories, such as hematopoietic lineage disruption, cell cycle arrest, and cytokine signaling. Results Oxaliplatin induced broad transcriptional suppression of erythropoiesis and lymphopoiesis, with 3,691 DEGs identified (FDR<0.05, |FC|>1.5). Upregulation of Cdkn1a and downregulation of E2f2 suggest G1/S cell cycle arrest, correlating with repression of key erythroid maturation genes (e.g., Spta1, Slc4a1, Alas2) and hemoglobin subunits (Hba-a1/2, Hbb-bs/t). Despite a ~3000-fold increase in renal Epo expression, bone marrow Epor was reduced, indicating erythropoietin resistance. B and T cell markers were also significantly downregulated, signifying a collapse in adaptive immunity. Notably, neutrophil populations were largely spared. Cytokine analysis in plasma revealed a pro-inflammatory shift with elevated TNF-α and reduced TGF-β, potentially exacerbating hematopoietic dysfunction. Conclusions Oxaliplatin induces a lineage-dependent suppression of hematopoiesis, driven by coordinated cell cycle arrest, metabolic stress, and disrupted cytokine signaling. RNA-seq analysis enabled integration of transcriptomic findings into coherent biological themes. These findings provide mechanistic insights into oxaliplatin’s hematologic toxicity linking bone marrow failure (potentially reversible) via interconnected inflammatory and metabolic pathways and may inform therapeutic strategies to minimize or restore myelosuppression in cancer patients.

Exploring the Mechanism of Complex Lemon-Angelica Sinensis-Boswellia Essential Oil on Anxiety Disorders with Melasma Through Network Pharmacology and Experimental Validation

The incidence rate of melasma is notably high among patients with anxiety disorders. Aromatherapy primarily influences the physiological and psychological states of individuals through the inhalation or application of essential oils, thereby facilitating the treatment or alleviation of various conditions. This study aims to explore the action mechanism of complex lemon-angelica sinensis -boswellia essential oil (CEO) in treating anxiety disorders with melasma. We investigated the active ingredients, targets, and pathways of CEO in relation to anxiety and melasma using network pharmacology. We employed cell assays and conducted nebulized essential oil inhalation tests on CUMS mice to validate the intervention effects of CEO on anxiety. A total of 28 active components, including neryl acetate, 3-butenylphthalide and octyl acetate, and 26 cross-targets, such as ESR1, CCND1 and PIK3CA, were identified. GO and KEGG pathway analyses indicated that these cross-targets were primarily involved in endocrine regulation, cell proliferation, and apoptosis, specifically through PI3K/Akt signaling pathway and calcium signaling pathway. The experimental results demonstrated that CEO significantly reduced the secretion of NO, TNF-a and IL-6, as well as the mRNA expressions of ESR1, CCND1 and PIK3CA in cells compared to the inflammatory cell model. Furthermore, CEO notably decreased the forced swimming immobility time of mice and the levels of IL-1β, ESR1 and CCND1 in hippocampus when compared to model mice. These findings suggest that CEO may regulate ESR1, CCND1 and PIK3CA through its citral, 3-butylphthalate and neryl acetate, thereby influencing endocrine function, cell proliferation and apoptosis, inhibiting inflammation and anxiety-like behavior in CUMS-induced mice.

Exploring the Nanomedicinal Features of Ayurvedic Bhasmas: Insights from Traditional Medicine

Ayurveda is a traditional and scholarly medical system practiced in South Asia since the Vedic period. It integrates science and philosophy to promote a healthy, happy and prosperous life. Ayurvedicbhasmas are classical formulations that contain non-toxic forms of metals and minerals, enriched with therapeutic metabolites. These bhasmas are produced through repeated trituration of metals and minerals with the extracts from potent Ayurvedic herbs, followed by intense heating at temperatures above 650 °C. The preparation process of bhasmas closely resemble top-down approach in nanoparticle synthesis, resulting in very fine calcined nano-powders. These powders are used effectively in Ayurvedic treatments for various ailments, particularly chronic diseases. Recent studies have highlighted that bhasmas possess antioxidant, anti-inflammatory, antibacterial, antiviral and antitumor properties and may serve as potential carriers for drug delivery. This paper aims to compare bhasma particles prepared by traditional and modern methods, explore the therapeutic benefits of different bhasmas, and investigate the nanomedicinal features of various Ayurvedicbhasmas.

Iatrogenic Extra-Capsular Extension of Knee Septic Arthritis Via Intra-Articular Joint Injection

Background Septic arthritis is a potentially limb or life-threatening joint infection that requires prompt recognition and intervention to reduce morbidity and mortality. While intra-articular joint injections are commonly performed for osteoarthritis and other arthropathies, they carry a rare but significant risk of iatrogenic infection, particularly when performed in the presence of unrecognized joint or periarticular infection. Case Presentation We report a case of a 52-year-old female with a history of traumatic brain injury and chronic right knee pain who developed severe knee swelling, pain, and systemic symptoms following an intra-articular corticosteroid injection performed without ultrasound evaluation/guidance. Post-procedure, she presented with fever, elevated inflammatory markers, and purulent knee effusion. Operative washout revealed a purulent tract extending from the knee joint capsule to the lateral thigh. Cultures from joint aspiration and intraoperative samples grew Streptococcus dysgalactiae. Blood cultures were negative. The patient reported frequent cat scratches to the affected knee and described an unusual sensation of the injection needle tracking laterally during the joint injection. She was treated with surgical drainage and a four-week course of amoxicillin, with full clinical recovery. Discussion This case highlights an unusual presentation of septic arthritis with extra-capsular extension likely due to iatrogenic needle tracking during joint injection. The causative organism, S. dysgalactiae, is an uncommon pathogen in septic arthritis, and the presumed source was contiguous spread from untreated cellulitis, possibly related to cat scratches/bites. The absence of predisposing comorbidities and negative blood cultures further support a local rather than hematogenous source. The case emphasizes the importance of thorough clinical evaluation and consideration of infection prior to joint injections, as well as the potential benefits of ultrasound guidance to minimize procedural complications. Conclusion Careful history, physical examination, and appropriate imaging are essential prior to joint interventions to avoid iatrogenic complications. This case illustrates the rare but serious risk of extra-capsular extension of septic arthritis following intra-articular injection and emphasizes the need for vigilance in identifying underlying infection before proceeding with invasive procedures.

A Case of Postoperative Hematoma Mimicking Giant Hydrocele

Background In adult males, non-communicating hydroceles are non fluctuant scrotal swellings that are formed when there is an imbalance of fluid secretion and absorption between the parietal and visceral layers of the tunica vaginalis. Giant hydroceles are a rare manifestation and have previously been classified as hydroceles that drain more than 1000 mL of fluid. In this report, we describe a case of a giant hydrocele requiring surgical management and highlight a review of the literature. Case Presentation A 34-year-old male presented with complaints of large right-sided scrotal swelling, accompanied by scrotal discomfort. Ultrasound of the right testicle revealed a large hypoechoic space with a complex collection and posterior displacement of the testicle, indicating a possible hydrocele. The patient was taken to the operating room for a right hydrocelectomy. Approximately 2 liters of fluid were drained from the sac.  Discussion Hydroceles are defined as straw-colored fluid collections within the parietal and visceral layers of the tunica vaginalis. Giant hydroceles, defined as fluid collections within the tunica vaginalis exceeding 1000 mL, are rare and the management of such cases is sparsely documented in the literature. While most asymptomatic fluid collections resolve spontaneously, larger collections with inflammatory changes within the testicular wall may require surgical intervention, either laparoscopic or open. 

Plasma TREM2 Levels, Alcohol Consumption, and Liver Enzymes in Patients with Alcohol use Disorder: A Sex-Dependent Relationship Involving MS4A6A Genetic Polymorphism

Alcohol use disorder (AUD) is the most prevalent substance use disorder. Excessive alcohol consumption leads to a range of health issues. We set out to identify inflammatory markers linked to alcohol consumption, which might ultimately offer novel insight into genetic underpinnings and have implications for alcohol-associated disease. Alcohol consumption and blood-based multi-omics data were collected by The Mayo Clinic Center for Individualized Treatment of Alcohol Dependence study. Plasma samples from patients with AUD were used for proteomics analysis using the OLINK “Explore Inflammation” panel (n=410). Liver enzymes were also measured. A genome-wide association study (GWAS) was performed to explore the relationship between genetic variants and plasma TREM2 levels. Our findings show thatplasma triggering receptor expressed on myeloid cells 2 (TREM2), a key gene associated with neurodegenerative disease, was the most significant signal correlated with alcohol consumption, and has also been associated with liver enzyme levels in patients with AUD. We identified the rs7232 single nucleotide polymorphism (SNP) in MS4A6A as a key genetic variant associated with plasma TREM2 levels, with the minor allele (A) linked to higher TREM2 levels and increased alcohol consumption, particularly in men. Furthermore, MA4A6A is an ethanol-responsive gene in a SNP-dependent manner, and the variant genotype of the rs7232 SNP was associated with lower expression for MA4A6A due to proteasome-mediated protein degradation. In summary, this study provides insight into the relationship between plasma TREM2 levels, alcohol consumption, and liver function in AUD patients, shedding light on genetic factors underlying alcohol-related diseases.

COVID-19-Induced Changes in the Fibrin Network of Pulmonary and Renal Microthrombi

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often causes coagulation disorders that affect highly vascularized organs, such as the lungs and kidneys. Objective The objective of this study was to report the histopathological findings of variations in the fibrin pattern of pulmonary and renal microthrombi in patients who died from SARS-CoV-2 infection. Methods Minimally invasive autopsies were performed on 40 patients to collect lung (n=40) and kidney (n=16) tissue samples. Histochemical and immunohistochemical staining techniques were used for histopathological analyses. Premortem laboratory data were obtained from the patients' electronic medical records. Results The lung tissue showed a patchy pattern, characterized by areas of both minimal and severe damage. The most significant histopathological finding was the detection of thrombi with fibrin structures organized into discrete star-shaped units, which were more frequently observed in areas with severe lung injury than in those with minimal lung injury (p = 0.012). Star-shaped fibrin structures were also observed in the renal glomerular capillaries. Immunohistochemical staining revealed the presence of platelets and the procoagulant proteins von Willebrand factor (VWF) and Factor VIII within the star-shaped fibrin thrombi. Patients with star-shaped fibrin thrombi had higher levels of the systemic inflammatory indicators C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR). Conclusion Our observations suggest that the inflammatory microenvironment resulting from SARS-CoV-2 infection may contribute to the formation of star-shaped fibrin units in the pulmonary and renal microthrombi.

Peripheral Third Cranial Nerve Palsy in A Patient With Pediatric Form of Multiple Sclerosis

Multiple Sclerosis has traditionally been considered an inflammatory and autoimmune disease of the central nervous system. However, peripheral cranial nerve involvement has been described previously in eight cases, raising the hypothesis of a disease spectrum between central and peripheral nervous system. We hereby present a case of a 12 years old girl diagnosed with Multiple Sclerosis who presents with complete unilateral third cranial nerve palsy. Complete clinical, laboratory and radiological work-up was consistent with demyelinating disease. We conclude that demyelination in Multiple Sclerosis can affect in some cases both the central and peripheral nervous system.

Challenges in Diagnosis of Neurosarcoidosis

Sarcoidosis is granulomatous autoinflammatory autoimmune remitting relapsing disease affecting every organ in the body, it is the most difficult disease to diagnose in the absence of serum or imaging biomarker. Differential diagnosis is broad which included inflammatory, infective, neurodegenerative and neoplastic, histological biopsy is the only confirmative marker, and even histological confirmation is not robust as infection, malignancy and some drugs can induce granuloma, the most common organs affected are lung, lymph nodes, skin, eyes, liver, and less commonly pituitary gland, bones, brain, peripheral nerves, and heart, causing bilateral hilar lymphadenopathy, granulomatous lymphadenitis.

Cervico-Vaginal Smear Abnormalities in a Patient with Pemphigus Vulgaris

Pemphigus vulgaris is an autoimmune-mediated blistering disease. Cervical involvement is rare. A 38 year old nulliparous woman with PV on oral prednisolone and azathioprine was referred to the Gynaecology service for an abnormal cervical cytological smear showing low-grade squamous intraepithelial lesion. She was asymptomatic, 10 pack-year smoker, and reported no abnormal vaginal bleeding. Colposcopy was unsatisfactory with inadequate visualisation of the transformation zone due to severe cervico-vaginitis. A small focus of aceto-white epithelium was seen, surrounded by peeling, friable epithelium. HPV DNA test was negative. Punch biopsy demonstrated metaplastic squamous epithelium with intraepidermal suprabasal blister formation with acantholysis. Well-vascularised dermal papillae lined residual basal cells, giving rise to a tombstone appearance. There was no evidence of CIN/CGIN or invasive malignancy. An ulcer was also seen in the left buccal region. Repeat colposcopy after 6 weeks showed a small ulcerated area at the biopsy site with rolled healing edges, and a separate small ulcer.  Cervical smear and colposcopy 6 months later were unremarkable. The incidence of cervical pemphigus vulgaris may be underestimated because women with pemphigus are often managed by Dermatologists without gynaecological input. In many published cases, cervical involvement was only detected after gynaecological examination due to symptoms such as dyspareunia, post-coital bleeding or vaginal discharge. Cervical smears of patients with pemphigus vulgaris  typically display acantholysis, which may be misinterpreted as reparative, inflammatory, or neoplastic change. There have been reports of unnecessary hysterectomy due to such misdiagnoses. Review by an experienced cyto-pathologist is required in the event of diagnostic uncertainty.

A Challenging Case of Groove Pancreatitis

Groove pancreatitis (GP) is a rare type of segmental chronic pancreatitis that affects the anatomical area between the pancreatic head, the duodenum, and the common bile duct, referred to as the groove area. Most patients with groove pancreatitis are males aged 40–50 years with a history of alcohol abuse. The prevalence of this condition was not determined due to rarity of cases.The clinical symptoms commonly reported were weight loss, upper abdominal pain, postprandial vomiting, and nausea due to duodenal stenosis. It is considered difficult clinically and radiographically to distinguish this form of chronic pancreatitis from other differential diagnoses of inflammatory conditions or malignancies affecting the pancreas or adjacent structures to that groove area. We report a challenging case of GP in an asymptomatic female patient during routine gastric ulcer screening. Our objective is to draw attention to this rare and atypical type of chronic pancreatitis and the importance for early detection on screening EGDs prior to its symptomatic sequelae and complications.

Deficiency of Adenosine Deaminase Type 2 (ADA2) DADA2 Masquerade as Lupus

DADA2 (deficiency of adenosine deaminase type 2) is an autoinflammatory autosomal recessive disease resulting from biallelic loss of function mutations in ADA2 gene. Clinical presentation and age of onset vary widely even among related patients, and variability of symptoms and severity manifestations include bone marrow failure, autoinflammation, immunodeficiency and vasculitis. Here, we report a case of young male with adult onset DADA2, who presented with fever, lower limbs skin rash, joint pain, and anemia resembling systemic lupus erythematous (SLE). DADA2 has an extremely variable clinical phenotype. It was described into three categories: inflammatory/vascular, immune dysregulation, and hematologic. However, the data is scant in describing autoimmunity phenotype in DADA2 and further studies are required to investigate the clinical correlation and presence of autoantibodies. We recommend genetic testing in cases with lupus-like disease especially if there is consanguinity between parents and family history of vasculitis.

Pyrexia And Liver Injury After A Second SARS-CoV-2 Vaccination: Macrophage Activation Manifested In Liver

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-Co V-2) has contributed to control of the coronavirus disease 2019 (COVID-19). On the other side, vaccination of SARS-CoV-2 could trigger autoimmune or inflammatory diseases. We present a 50-year-old female with well-controlled optic neuromyelitis with prednisolone (PSL) maintained at a dose of 2.5 mg/day. She ran a fever and liver injury was indicated 5 weeks after a second COVID-19 vaccination (BNT162b2 mRNA/Pfizer ). Liver biopsy showed accumulation of macrophages around the central veins, identified using anti-CD68 antibodies. As the treatment, cyclosporine A improved liver injury. COVID- 19 vaccination may have triggered liver inflammation due to cytokine storm via macrophage activation in the liver.

Cross-Reactivity between COX-2 Inhibitors in Patients with Cross-Reactive Hypersensitivity to NSAIDs

The safety of cyclooxygenase (COX)-2 inhibitors has been tested in patients who had cross-reactive hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs). However, these studies have been mainly done before the current classification of NSAID hypersensitivity and cross-reaction between COX-2 inhibitors has been rarely reported.We aimed to assess tolerability of COX-2 inhibitors and to evaluate the cross-reactivity between them in cross-reactive phenotype of NSAID hypersensitivity. The diagnosis was based on clinical features, reliable history of HSRs to at least two chemically different NSAIDs, and/or positive provocation tests with implicated NSAIDs in 151 patients. Single-blind, oral challenges with 1/4 and 3/4 divided doses of placebo, nimesulide, meloxicam, and celecoxib, as COX-2 inhibitors, were performed. The most common cross-reactive phenotype was NSAID-induced urticaria/angioedema (56.3%). Positive reactions to meloxicam, nimesulide, and celecoxib challenges were observed in 23/140 (16.4%), 7/33 (21.2%), and none of six patients, respectively. Overall, 24 patients were tested with two, one was tested with three COX-2 inhibitors. Six (31.6%) of 19 patients with meloxicam intolerance reacted to nimesulide provocation. Nimesulide, meloxicam, and celecoxib appeared safe alternatives in cross-reactive phenotypes of NSAID hypersensitivity. Although celecoxib has the most favorable tolerability, cross-reactivity among COX-2 inhibitors seems to be possible.

Osteoarthritis Depression Impacts and Possible Solutions Among Older Adults: Year 2021-2022 in Review

Background Osteoarthritis, a serious joint disease, said to represent a generally declining state of wellbeing and function among many older adults has been shown to be affected to a considerable degree by various negative beliefs and inactions rather than degradation alone. Aim This review examines the case of depression as this pertains to the older adult with osteoarthritis of one or more joints. Specifically, the most up to date information on this topic was sought, as care improvements over the past decade have not shown any impactful population wide results. Method Reviewed were relevant 2021-2022 research and review articles specifically pertaining to what is being observed currently by researchers as far as osteoarthritis-depression linkages goes, as these may reveal opportunities for more profound research, and practice-based endeavors. Results In line with 60 years of prior research, it appears a clinically important role for depression in some osteoarthritis cases cannot be ruled out. It further appears that if detected and addressed early on, many older adults suffering from osteoarthritis may yet be enabled to lead a quality life, rather than a distressing and excessively impaired state of being. Those older osteoarthritis cases requiring surgery who suffer from concomitant depressive symptoms are likely to be disadvantaged in the absence of efforts to treat and identify this psychosocial disease correlate. Conclusion Providers and researchers are encouraged to pursue this line of inquiry and begin to map clinical osteoarthritis measures with those that can track cognitive patterns, musculoskeletal, features and inflammatory reactions along with valid depression indicators among carefully selected osteoarthritis sub groups.

Duodenocolic Fistula: A Rare Complication of Gastrointestinal Tuberculosis

Introduction Benign duodenocolic fistula (DCF), also known as a non-malignant fistula between the duodenum and colon, with or without cecum-involvement, is an unusual complication of different gastrointestinal (GI) diseases 12. Case This is a case of a 28-year-old Filipino female who presented with periumbilical pain for five months, with associated anorexia, fever, and weight loss. Biopsy showed chronic granulomatous inflammation with caseation necrosis and Langhan’s type giant cells consistent with tuberculous etiology (Figure 6 and Figure 7). Category I Anti-TB treatment for six months was started and the service planned to repeat both colonoscopy and CT-scan after the initial round of anti-TB treatment. Conclusion Benign duodenocolic fistula in the form of extrapulmonary TB is a rare GI finding that is triggered by inflammatory processes. Proper management in this case was to treat the underlying TB infection which is endemic in the Philippines.

Cytokine Profiling in COVID-19 Patients in a Tertiary Hospital in Saudi Arabia; the Pre-Storm Phase

Background As COVID-19 immunomodulation has been a part of interest for studies, it has been found that severe coronavirus disease 2019 (COVID-19) is associated with hyper-inflammatory response and increased levels of interleukin-6 (IL-6) and interleukin-10 (IL-10). This can progress to cytokine storm syndrome and eventually development of acute respiratory distress syndrome (ARDS). Interleukin-1 receptor antagonist (IL-1RA) is a protein that is a member of the interleukin 1 cytokine family. Monocyte chemoattractant protein 1 (MCP1) is a small cytokine that belongs to the CC chemokine family. Interferon gamma-induced protein 10 (IP-10) is a protein secreted by several cell types in response to Interferon-Gamma (IFN-γ). All of these have roles in the immune response and eventually development of a cytokine storm. Methods Serum levels of IL-1RA, MCP-1 and IP-10 were measured in a cohort of 21 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on admission to a tertiary care hospital in Riyadh, Saudi Arabia, as well as in an approximately age-sex matched group of 4 uninfected controls. The study population was classified into severe, moderate, mild and controls. Results Serum levels of IL-1RA, MCP-1 and IP-10 were found to be elevated before the clinical deterioration. Conclusion These cytokines may play a role in early detection of disease severity especially in the pre-storm phase. Medications that target cytokines may prevent the development of an overt cytokine storm.

A Theory on the Impact of Copper and Micronutrients Against COVID-19 in Humans

Copper (Cu) has a strong impact on the function of the immune system through several different pathways. These impacts include helping the function of monocytes, neutrophils, and macrophages, and enhancing Natural Killer cells’ activities. Cu also has a role in antimicrobial properties and inflammatory response. It is also important for IL-2 production and response, which is a component of adaptive immune cells. Additionally, Cu has multiple roles in both proliferation and differentiation of T cells and is involved in the production of antibodies. Cu deficiency can even lead to "increased viral virulence"1. Copper has a long history of use in medicine, and has continued to be used for purification of water, including use in hospitals to prevent legionnaires disease. The CDC pre released information on a study completed in March 2020 on the lifespan of COVID-19 on different surfaces which included its lifespan on copper, where it was completely dead within 4 hours. In addition, "Several reports demonstrated that Cu deficiency weakens the human immune response" 2. Given the multiple avenues of impact, it has been suggested that Cu supplementation, within recommended levels, be given to individuals who are low in Cu to help them fight off COVID-19. It is also possible that Cu supplementation, within recommended levels, may help prevent COVID-19 infection, or help individuals who are not low in Cu to fight off COVID-19 infection. However, dosage would have to be carefully managed, as excess levels of Cu can lead to both neurodegenerative and neurodevelopmental diseases.

Ameliorative Potential of Chlorogenic Acid on Rotenone-Induced Neurotoxicity in Drosophila Melanogaster Model

Chlorogenic acid (CA), abundantly found in green coffee beans, is a phenolic compound with antioxidant and anti-inflammatory properties amongst others. Exposure to rotenone, a natural pesticide, induces Parkinsonism (a type of neurodegeneration) through the induction of mitochondria dysfunction and oxidative stress. Phytochemicals with antioxidant properties may be promising in attenuating this condition. In this research, the ameliorative role of CA on rotenone-induced toxicity in Drosophila melanogaster was evaluated. Drosophila melanogaster (Harwich strain, 1- 3 days old) was used. 6 groups of five vials each with 50 flies/vial were exposed to CA (0; control (2% ethanol), 7.5, 15, 30, 45 and 60 mg/kg diet) for 28 days in the longevity analysis. A 28-day survival assay was carried out with rotenone (0, 250 and 500 μM). CA (30 mg/kg diet) was selected to evaluate its ameliorative potential on rotenone. For the study, the flies were divided into four groups of five vials each and exposed to CA and rotenone; Group A- control (2% ethanol), Group B- CA only, Group C- rotenone only and Group D- CA (30 mg/kg diet)+ rotenone (500 μM)for 7 days. Thereafter, the homogenate was evaluated for oxidative stress status, rate of emergence, negative geotaxis and acetyl cholinesterase activity. CA (30 mg/kg diet) extended the lifespan of flies by 21.4%. Also, CA ameliorated rotenone-induced perturbation in catalase, glutathione-S-transferase and acetyl cholinesterase activities, total thiol and glutathione levels, and behavioral deficit (p < 0.05). CA may have ameliorative effect against rotenone-induced toxicity and Parkinsonism.

Rosemary (Salvia rosmarinus): Health-Promoting Benefits and Food Preservative Properties

Natural food preservatives in the form of herb extracts and spices are increasing in popularity due to their potential to replace synthetic compounds traditionally used as food preservatives. Rosemary (Salvia rosmarinus) is an herb that has been traditionally used as an anti-inflammatory and analgesic agent, and currently is being studied for anti-cancer and hepatoprotective properties. Rosemary also has been reported to be an effective food preservative due to its high anti-oxidant and anti-microbial activities. These properties allow rosemary prevent microbial growth while decreasing food spoilage through oxidation. Rosemary contains several classes of compounds, including diterpenes, polyphenols, and flavonoids, which can differ between extracts depending on the extraction method. In particular, the diterpenes carnosol and carnosic acid are two of the most abundant phytochemicals found in rosemary, and these compounds contribute up to 90% of the anti-oxidant potential of the herb. Additionally, several in vivo studies have shown that rosemary administration has a positive impact on gastrointestinal (GI) health through decreased oxidative stress and inflammation in the GI tract. The objective of this review is to highlight the food preservative potential of rosemary and detail several studies that investigate rosemary to improve in vivo GI health.

Analgesic and Anti-Pyretic Activities of the Root Bark of Rutidea Parviflora (Rubiaceae)

This study aims at investigating the antipyretic activity of different solvent fractions of the root bark of Rutideaparviflora(Rubiaceae). This plant is used ethno-botanically by the people of Ethiope East-West Local Government Area of Delta State, Nigeria to treat various ailments such as inflammation, fever and pain. This necessitated this research to validate its local use, due to the scanty literature and information present about this plant. It has also shown some anti-cancer and anti-inflammatory activity in previous researches. The present study is a randomized control study. Acetic acid induced writhing was employed for analgesic testing. Acetic acid was used to induce writhing in Wistar rats which were divided into fourteen (14) groups. The groups were administered extracts and fractions of the plant (200 mg/kg and 400 mg/kg). The animals were observed for number of writing movements and the percentage writhing was calculated. Baker’s yeast induced pyrexia was employed for the antipyretic testing. The animal groups were administered extracts and fractions of the plant (200 mg/kg and 400 mg/kg), with Paracetamol as the standard drug (100 mg/kg) and Normal saline (control) for both experiments. The body temperature of the rats was measured rectally over a period of five (5) hours. All values of P<0.05 were taken as significant. The organic extract, aqueous extract and various fractions (n-hexane, ethyl-acetate, n-butanol and aqueous) produced significant inhibition of writhing responses and pyrexia in a dose dependent manner and time dependent manner respectively. The aqueous extract at a dose of 400mg/kg showed the greatest reduction in writhing, 91.58% compared to the standard drug (paracetamol) which may suggest that the fraction possesses better efficacy than paracetamol as an analgesic. The observed activities could be attributed to these bioactive compounds: Palmatine, Urs-12-ene-24-oic-3-oxo-methyl ester and Gallic acid contained in R. parviflora.

Evaluation of Anti-oxidation and Therapeutic Effect of Biofield Energy Healing Based Novel Test Formulation Using TNBS (Tri Nitro Benzene Sulfonic Acid) - Induced Ulcerative Colitis in Sprague Dawley Rats

The aim of the study was to evaluate the antioxidant potential of Biofield Energy Healing (the Trivedi Effect®) based test formulation using TNBS-induced colitis animal model. Each ingredient of the test formulation was divided into two parts. One part was denoted as the control without any Biofield Energy Treatment, while the other part was treated with Biofield Energy Treatment by Mr. Mahendra Kumar Trivedi and defined as the Biofield Energy Treated test formulation. The colon tissue was used for the estimation of anti-oxidation activity for catalase (CAT), glutathione (GSH), lipid peroxidation (LPO) product, myeloperoxidase (MPO), superoxide dismutase (SOD), and glutathione peroxidase (GPx) using standard procedure. The antioxidant results showed that the CAT level was significantly increased by 95.4% (p≤0.001), 72.3%, 47.6%, and 13.9% in the Biofield Energy Treated test formulation (G5), Biofield treatment per se to animals (-15 days)(G6), Biofield Energy Treatment per se to animals plus Biofield Energy Treated test formulation (-15 day) (G8), and Biofield Energy Treatment per se to animals plus untreated test formulation (G9) groups, respectively as compared to the untreated test formulation group (G4). Further, colon GSH activity was found to be significantly increased by 23.2% (p≤0.05) 15.4%, and 15.5%, in G5, G6, and G9 groups, respectively with respect to G2 group. In addition, colon LPO activity data suggested that it was decreased by 12%, 17%, 18%, and 19.1% in G5, G6, Biofield Energy Treated test formulation (-15 day) (G7), and G8 groups, respectively, as compared with the G2 group. The level of MPO showed a significant (p≤0.001) reduced level by 27.9%, 22%, 14.5%, 16.6%, and 25.3% in G5, G6, G7, G8, and G9 groups, respectively as compared with the G2 group. The level of colon SOD was increased by 16.7% and 14.2% in the G5 and G9 groups, respectively as compared with the untreated test formulation, G4 group. Colon GPx level was increased by 177.6%, 71.4%, 71.4%, 161.2%, and 114.3% in G5, G6, G7, G8, and G9 groups, respectively as compared with the G2 group. Thus, it can be concluded that the Trivedi Effect®-Consciousness Energy Healing based test formulation and Biofield Energy per se has significant colon anti-oxidation profile, which can be used to improve many autoimmune and inflammatory diseases, stress management and prevention, and anti-aging by improving overall health.

Evaluation of Gall Bladder Mucosal Changes in Relation to the Type of Stones in Patients Undergoing Laparoscopic Cholecystectomy: A Retrospective Study of 394 Patients

Background and Aim Gallbladder (GB) cancer is a highly fatal malignancy and approx. 10% new cases are diagnosed every year in India. The GB cancer has poor prognosis due to progressive nature. Understanding of risk factors that lead to GB development is urgently required for better management of the disease. Presence of stones in gall bladder generates varied mucosal reactions, which leads to different types of histopathological changes in mucosa. Here, our aim is to study the correlation between various types of mucosal responses e. g. inflammation, hyperplasia, metaplasia and carcinoma with different characteristics e. g. number and morphology of gallstones both in males and females. Materials and Methods A retrospective study of gallstones was performed on 438 cases of cholecystectomies operated laparoscopically based on the histological changes. Out of 438 cases, 394 (89.95%) were associated with gallstones and the rest 44 (10.05%) belonged to acalculous cholecystitis. The mucosal changes in calculous gall bladder were studied in 394 cases and its correlation with number and types of observed gallstones were evaluated. Tissue sections were taken from the fundus, body, neck and abnormal area of gallbladder for histopathological studies. Results Our study has revealed the higher incidence of inflammatory changes in males, while gall bladder hyperplasia, intestinal metaplasia and cancer cases were found mostly in females. Conclusion Our study showed that changes in the number and morphology of gallstones are directly associated with the mucosal changes in gallbladder e.g. inflammation, hyperplasia, metaplasia and gall bladder carcinoma.

Analysis of Isotopic Abundance Ratio of Consciousness Energy Healing Treated Metronidazole Using LC-MS and GC-MS Spectrometry

Metronidazole is an antibiotic and useful for the antibacterial and antiprotozoal medication. This study was performed to investigate the impact of the Trivedi Effect®-Biofield Energy Healing Treatment on the structural properties and the isotopic abundance ratio of metronidazole using LC-MS and GC-MS spectroscopy. Metronidazole sample was divided into two parts, one part of metronidazole was considered as control (no Biofield Energy Treatment was provided), while the second part was treated with the Trivedi Effect®-Consciousness Energy Healing Treatment remotely by a renowned Biofield Energy Healer, Alice Branton and termed as a treated sample. The LC-MS spectra of both the samples of metronidazole at the retention time (Rt) 2.61 minutes exhibited the mass of the protonated molecular ion peak at m/z 172 M+H+ (calculated for C6H10N3O3+, 172.07). The LC-MS based isotopic abundance ratio of PM+1/PM (2H/1H or 13C/12C or 15N/214N or 17O/16O) in the treated metronidazole was significantly increased by 8.24% compared with the control sample. Thus,13C, 2H, 15N,and17O contributions from (C6H10N3O3)+ to m/z 173 in the treated sample were significantly increased compared with the control sample. The GC-MS based isotopic abundance ratio of PM+1/PM in the treated metronidazole was significantly increased by 5.92% compared with the control sample. Hence,13C, 2H, 15N, and217O contributions from (C6H9N3O3)+ to m/z 172 in the Biofield Energy Treated sample were significantly increased compared with the control sample. However, the isotopic abundance ratio of PM+2/PM in the treated metronidazole was significantly decreased by 18.2% compared with the control sample. Hence,18O contributions from (C6H9N3O3)+ to m/z 173 in the treated sample were significantly decreased compared with the control sample. The isotopic abundance ratio of PM+1/PM (2H/1H or 13C/12C or 15N/14N or 17O/16O) and PM+2/PM (18O/16O) in the treated metronidazole was significantly altered compared to the control sample. From the results, it can be hypothesized that the changes in isotopic abundance and mass peak intensities could be due to changes in nuclei possibly through the interference of neutrino particles via the Trivedi Effect® - Consciousness Energy Healing Treatment. The new form of treated metronidazole would be better designing novel pharmaceutical formulations that might offer better therapeutic response against bacterial and protozoal infection in the vagina (bacterial vaginosis), stomach (giardiasis, trichomoniasis, pseudomembranous colitis), joints (pelvic inflammatory disease), liver, skin, brain, and respiratory tract, aspiration pneumonia, rosacea, intra-abdominal infections, lung abscess, fungating wounds, periodontitis, amoebiasis, oral infections, etc.

Reversible Posterior Encephalopathy Syndrome and Related Factors: Clinical Cases Study

Background Reversible posterior encephalopathy syndrome (RPE) is a clinical and radiological entity characterized by the acute or subacute fitting of symptoms covering headache, vomiting, visual disturbances, seizures and impairment of consciousness. The pathophysiology of RPE syndrome is poorly described. RPE syndrome is characterized by a reversible cerebral edema of often posterior topography in magnetic resonance imagery (MRI). Cases Presentation We consider RPE syndrome four cases under various conditions that are known as airplane flight, hypertension, non-steroidal anti-inflammatory medication, pregnancy and oldness with several pathologies. The RPE was described with several symptoms like headaches, vomiting, focal motor deficit, paresthesia, seizures, disorders of consciousness and photophobia. The imagery findings were varying from cortical hypersignals in Flair sequences to edema of both cortex and sub cortex. The outcome was good with a complete regression of symptoms and imagery lesions. Conclusion The pathophysiological mechanism of RPE syndrome remains unknown. High blood pressure, renal failure and drugs (anti-depressants, NSAIDs, immunosuppressants) are the most etiological factors. The diagnosis is based on clinical arguments and brain MRI. The main location is posterior. The clinical outcome was good with all the patients in our study, no recurrence was noted.

The Vascular Convolutions-Papillary Endothelial Hyperplasia

Intravascular papillary endothelial hyperplasia is an exceptional, benign, inflammatory, vascular neoplasm delineating papillary configuration engendered from reactive proliferation of damaged endothelial cells, while being confined to a thrombus. Initially scripted by Pierre Mason in 1923, the tumefaction was denominated as an intra-luminal lesion within an ulcerated, haemorrhoidal vein and designated as “hemangio-endotheliome’ vegetant’ intravasculaire”(1). The neoplasm is additionally nomenclated as Masson’s tumour,  Masson’s pseudo-angiosarcoma, endovascularite proliferante  thrombopoietique, intravenous atypical vascular proliferation, intravascular angiomatosis, vascular angiomatosis, intravascular endothelial proliferation, reactive papillary endothelial hyperplasia or intravascular papillary endothelial hyperplasia. The papillary neoplasm is associated with deposition of fibrin and thrombotic substances within a painful, ulcerated.

Pharmacological Importance of Sage and Oregano 

Sage and Oregano, both are well-known culinary herbs with potential medicinal uses. Sage is mostly used to cease wounds bleeding, treating sores, swelling, cough and ulcers back in the first century and was called as the fertility drug since it reduces excessive bleeding during menstruation. On the other hand Oregano was found to be effective in treating stomach discomforts, bacterial/fungal infection, inflammatory bowel disease etc. Therefore due to their therapeutic and native applications, Sage and Oregano is of high economic worth.

Pilot Study: Impact of a Gluten-Free Diet on Symptoms and Severity of Fibromyalgia

Fibromyalgia (FM) is a condition of chronic and widespread pain, with several associated symptoms. Previous studies suggested that gluten could influence the severity and frequency of FM symptoms. This work aimed to assess the impact of a gluten-free diet (GFD) in the symptoms and severity of this disease. Fourteen patients with previous FM diagnosis were kept on a gluten-free diet for eight weeks (Phase 1). After that, they were held on the gluten-free diet and received capsules of isolated rice protein (placebo) for seven days, followed by capsules containing 8.4g/day vital gluten for additional seven days (Phase 2). Questionnaires evaluating the number and severity of FM symptoms, the impact of FM on daily routine as well as inflammatory blood markers were assessed in each phase. Results showed that after eight weeks of GFD, we observed a reduction in the impact of FM on daily routine and number of symptoms and sensitive points. However, a seven days challenge with 8.4g of gluten did not worsen these symptoms or the inflammatory markers compared with the placebo challenge. We concluded that the gluten-free diet was associated with the attenuation of main symptoms and improvement of life quality in FM patients. Nonetheless, gluten challenge had no impact on those parameters, suggesting that gluten is not the major dietary component responsible for these improvements. Further studies are needed to elucidate the relationship between gluten intake and fibromyalgia.  

Implementation of an Elemental Diet in Five Children Diagnosed with Autism Spectrum Disorder Presenting with Gastrointestinal Disease: A Brief Report

Autism Spectrum Disorder (ASD) is a developmental disorder characterized by impaired communication and social interaction. Children with ASD are frequently diagnosed with gastrointestinal (GI) issues, including inflammatory bowel disease (IBD), gastroesophageal reflux, abdominal pain, diarrhea, and constipation, although the association between ASD and GI conditions is unclear. Underlying nutritional deficiencies are more common in children with ASD, and increase the risk of them developing medical conditions secondary to the behavioral diagnosis. This objective of this study was to examine the use of an elemental diet (ED) in the treatment of gastrointestinal disease in 5 children with ASD ages 2-21 years of age. In the study participants, the ED was well-tolerated with improvements in anthropometric measures, nutritional markers, and/or GI functioning reported after 12 weeks of intervention. Further research to advance the development of specific evidence-based guidelines in the management and treatment of gastrointestinal concerns in the ASD population is warranted.

The Elliptical Aggregates – Idiopathic Granulomatous Mastitis

Idiopathic granulomatous mastitis was initially scripted in 1972 by Kessler and Wolloch and is cogitated as an infrequent, benign, chronic inflammatory disorder. It commonly implicates females of reproductive age group, especially women who have breast fed in the preceding five to six years. Idiopathic granulomatous mastitis is commonly discerned in Asia and Mediterranean region although true incidence is undetermined. Diverse ethnicities delineate a diverse disease prevalence. Elimination of adjunctive causes of granulomatous inflammation makes idiopathic granulomatous mastitis a diagnosis of exclusion. As per the natural history, idiopathic granulomatous mastitis is designated as a self limiting disorder 1.

Capsaicin: A Potential Therapy Adjuvant for Intestinal Bowel Disease

Most of the patients with inflammatory bowel disease avoid pepper or spicy food, alleging that this condiment causes anal sensation of burning and accelerates intestinal movements. Capsaicin is the main bioactive component of peppers responsible for the pungent flavor that characterizes red peppers. Capsaicin has been related to several biological effects, including decreased body fat, antianti-inflammatory, anticarcinogenic, antioxidant activites and modulator of intestinal motility. These actions mostly are due to its role as an agonist of the transient receptor potential vanilloid 1 (TRPV1), expressed in the mesenteric nervous system and epithelial cells of the colon. Nonetheless, the anti-inflammatory action of capsaicin is also related to its role in activating the peroxisomal proliferator-activated receptor gamma (PPAR-γ). Topical capsaicin formulations are already used for pain management, but oral administration of capsaicin is rare. Here, we discuss the main actions of capsaicin that could interfere with the symptoms and severity of IBD. Although animal experiments suggest a beneficial effect of capsaicin on colitis, clinical studies exploring the potential analgesic and anti-inflammatory of capsaicin on Crohn or Ulcerative Colitis are scarce. We concluded that there is no evidence that capsaicin aggravates IBD symptoms or severity. On the opposite, experimental studies suggest that capsaicin could reduce intestinal inflammation by a mechanism that could involve not only the TRPV1 receptor but also PPAR γ. However, clinical studies are still scarce, and data regarding capsaicin concentrations, routes of administration, and long-term side-effects need to be better understood before its use.

Interaction Between Ator and Fennel in the Treatment of Obesity in Rats

Obesity can be defined as a condition of abnormal or excess fat accumulation in adipose tissue, to the extent that health may be impaired. Fennel is one of the oldest spice plants which widely grows in arid and semi-arid and due to its economic importance and pharmaceutical industry usage. This plant has anti-inflammatory and analgesic effect and is effective in gastrointestinal disorder treatment. The aim of the present study was to evaluate the phytochemical characteristics and therapeutic properties of this medicinal plant. The current study demonstrates that the alteration induced by high fat diet causing changes in blood parameters. These changes are exhibited through a decrease in RBCs, Ht, Hb and platelet and these changes could be due to oxidative stress, which lead to lipid peroxidation in RBCs membranes, auto oxidation of hemoglobin. As regards the total WBCs, lymphocytes and monocytes showed marked decrease. While a distinct increase in the percentage of neutrophils and eosinophil. The present, demonstrates that rats treated with (fennel), (ator) and (fennel with ator) exposure provided significant protection to the altered hematological variables. The effect of the treatment with fennel and ator more effect than fennel only and ator only. The finding of this study indicates that the concentration of Malondialdehyde (MDA) and Myeloperoxidase (MPO) in liver homogenates of the fennel and ator group significant decrease than group (3) and group (4) and the obese group. There is a growing awareness that obesity is a prime risk factor for the development of dyslipidemia profile and that oxidative stress may play a role in various adverse effects of obesity.

Acute Peritonitis: A Rare Complication Revealing Intestinal Tuberculosis

Intestinal tuberculosis diagnosis is often difficult because of non-specific symptoms, miming many other conditions such as malignancy, infectious disease, and inflammatory bowel disease. Free intestinal perforation is an uncommon but life-threatening complication of intestinal tuberculosis, associated with high morbidity and mortality.

Rosenthal's Disease (Hemophilia C or factor XI Deficiency) Revealed by Chronic Epistaxis: The First Observation in Sub-Saharan Africa.

Objective Rosenthal's disease (RD) is a rare constitutional hemorrhagic disorder defined by factor XI deficiency. It is clinically characterized by the presence of minimal haemorrhage. We report the first observation of RD in Togo. Observation Mrs. G. A., 45 years old with no particular pathological antecedents, was referred for anemia in a context of chronic epistaxis. It was a spontaneous anterior exteriorization epistaxis often of great abundance, rocking and which evolved episodically. The patient received several transfusions for anemia. The ear-nose-throat examination was normal and a sinus CT scan found only an inflammatory process of the right maxillary sinus. The blood count showed microcytic severe anemia (2,2g/dl). Hemostasis tests showed a prolonged aPTT (57,9 seconds). Clinical examination documented an anemic syndrome with dry skin. Iron deficiency was found. The hemostasis balance confirmed aPTT elongation. Coagulation factors activity showed normal VIII and IX level, but moderate decrease of factor XI (32%). The family survey was not possible (orphan patient). It is recommended the setting under fresh frozen plasma (FFP) in case of a new episode. Follow-up is in progress. Conclusion In the event of any hemorrhagic syndrome, the isolated elongation of the aPTT must lead to a systematic analysis of intrinsic pathway factors

Long Non-Coding RNAs Emerging as Potential Epigenetic Biomarkers for Tobacco and/or Alcohol-Induced Head and Neck Cancer

Head and Neck cancer (HNC) is one of the most prevalent and lethal cancer globally. The incidence of tobacco-induced HNC is gradually increasing in low and middle income countries. Among the various causative factors associated with HNCs, tobacco and alcohol play synergistic effect and are frequently associated with the risk of HNC. Tobacco-induced HNCs show distinct genetic and epigenetic alterations leading to different clinical outcomes in comparison to HPV-infected HNCs. Tobacco-induced HNCs are often associated with tumor aggressiveness, poor prognosis and low or nil prevalence of HPV infection. Apart from carcinogenic effects of these causative factors (use of tobacco products, alcohol intake and HPV or EBV infections), recent studies show that exposure to these factors alter/disrupt the regulation of non-coding RNAs including the long non-coding RNAs (lncRNAs). Altered lncRNA regulation is brought about by signalling networks that regulate cellular differentiation, apoptosis, angiogenesis and inflammatory pathways which play key functions in the genesis of different cancers including HNCs. There are numbers of studies supporting the emerging role of lncRNAs in development of HNC; however, reports connecting lncRNAs expression and addiction habits in HNC are still preliminary and sparse. Therefore, identification and characterization of lncRNAs that are differentially expressed upon exposure to risk-factors can serve as unique therapeutic targets and potential biomarker(s) for effective treatment of HNC subtypes. In this short review, we briefly reviewed the emerging role of lncRNAs in tobacco and alcohol induced HNCs.

Cytokines Level (Il8 and Il17) in Pregnant Women with Toxoplasmosis in Khartoum State

Toxoplasmosis is one of the most important zoonotic diseases worldwide caused by Toxoplasma gondii that leads to abortion or hydrocephalus during pregnancy. It’s a comparative cross-sectional one designed to assess immunoglobulins and cytokines in pregnant women. A total of 300 venous blood samples were collected from each pregnant woman and centrifuged to obtain serum. Patient’s information was recorded in a questionnaire previously designed for the purpose of analysis. In addition, 40 uninfected women were enrolled in the study as control group to assess the level of IL8 and IL17 cytokines. The overall seropositive rate of Toxoplasma gondii infection was 22.6%. Within the positive cases of study population, only 16 and 13 showed positive results of IL8, IL17 respectively. The results showed highly significant increase in the mean serum level of IL8 (210.25pg/ml) and IL17 (203.15 pg/ml) when compared to the control group who showed 68.9 pg/ml and 54.8 pg/ml respectively. The serum level of proinflammatory cytokines investigated in this study seems to be increased in patients with serological evidence of Toxoplasma gondii infection. Our study concludes that IL-17 and IL-8 involved in the induction of inflammation and toxoplasmosis disease.

A Case Series of Resolving Vitreous Haemorrhage in the Setting of Diabetic Retinopathy

This case series presents 2 patients (67 and 58 year old females) with resolving vitreous hemorrhage in the setting of diabetic retinopathy. Both patients had around 50% of the retina still visible and the hemorrhage was confined at the posterior vitreous cavity near the retina, hence, a partial pan retinal photocoagulation (PRP) was feasibly applied. On B-scan, both cases showed a liquified vitreous with posterior vitreous detachment (PVD). For both patients, vitreous hemorrhage resolution occurred at less than 4 months from onset and consequently PRP was completed. Vitreous hemorrhage differs with bleeding in other tissues due to the presence of vitreous collagen matrix which promotes rapid clotting and hinders resolution of hemorrhage by preventing passive diffusion and delay in inflammatory cellular response. The prognosis for clearing hemorrhage was better when the fundus reflex was brighter and the retina adjacent to the ora serrata was visible. Clearing occurred sooner when hemorrhage was retrohyaloid rather than in the vitreous gel. In diabetic eye, the vitreous undergoes metabolic derangements resulting in premature liquefaction and abnormal vitreoretinal adhesion leading to traction and membrane formation. Partial PVD has also been associated with higher rate of diabetic retinopathy progression since it serves as scaffold for growth of neovascular tufts.

Acute pneumonia: infection or inflammation in the lung?

This commentary examines pneumonia as infection and inflammatory syndrome, parsing diagnostic criteria and implications for antimicrobial stewardship.

Immunodetection of Leishmania Infantum in the Subungual Area of Dogs with Visceral Leishmaniasis

Onychogryphosis is one of the main clinical findings in dogs with visceral leishmaniasis (VL); however, research focusing on the subungual area of infected dogs is scarce. This study aims to assess the subungual area of dogs with VL that presented or not onychogryphosis by means of histopathological analyses and immunohistochemical studies (parasite burden). The third digit of the thoracic and pelvic limbs of Leishmania infantum naturally infected dogs was collected regardless of sex, breed or age. The animals were split into two groups, dogs with onychogryphosis (G1; n=7) and without onychogryphosis (G2; n=9). The digits were evaluated in four areas (dorsal epidermis/dermis, ventral epidermis/dermis, dorsal matrix/dermis and ventral matrix/dermis). All lesions observed (mononuclear inflammatory infiltrate, vacuolar degeneration of basal keratinocytes, dermoepidermal clefting and pigmentary incontinence) were present in both groups, being more severe in the digits of G1 group. Immunostaining of the amastigote forms of Leishmania infantum were observed in the different areas of the digit, with statistical difference between the dorsal epidermis/dermis area and the dorsal matrix/dermis of G1 group. In conclusion, the main histopathological alteration of the digit of dogs with VL is mononuclear inflammatory infiltrate and parasite burden, especially in cutaneous tissue adjacent to the nail matrix. This aspect can influence the onychogryphosis development, due to the presence of the parasite and by inflammatory mediators released in the nail microenvironment.

Oregano (Origanium Vulgare) Extract for Food Preservation and Improving Gastrointestinal Health

The Mediterranean diet has long been known to provide a variety of health benefits including cardiovascular protection, cancer prevention, and lowering gastrointestinal inflammation. Oregano (Origanium vulgare) is an herb prominent in the Mediterranean diet, and has been shown to possess several bioactive properties including anti-oxidant, anti-microbial, anti-inflammatory, and analgesic properties. The anti-oxidant and anti-microbial properties of oregano also make it a strong candidate as a natural food preservative. Because of the recent public concern with synthetic food preservatives, natural alternatives are increasingly being evaluated for effective food preservation. Oregano extract (OE) and essential oil (OEO) are two such agents that have shown promise as natural food preservatives. Additionally, oregano is being evaluated for its positive effect on gastrointestinal health, suggesting an additional benefit of food preservation with oregano. This review will describe in vitro studies related to the anti-microbial and anti-oxidant properties of oregano along with food preservation studies with oregano in various model food matrices. The major phytochemical content reported for OE and OEO will also be outlined to highlight the importance of characterizing the extract that is used, since the extraction process can have a significant effect on the phytochemicals therein. Finally, in vivo studies that investigate the gastrointestinal health benefits of oregano, specifically against inflammation, will be addressed to describe the role of oregano on gastrointestinal health.

The use of Dermacell® in Fingertip Injury

Matrices or tissue scaffolds provide a collagen structure for tissue remodelling while the removal of viable cells aims to minimize or prevent inflammatory or immunogenic response. Allograft collagen scaffold can support the patient’s own cellular ingrowth, ingeneered to minimize an immune response and to yeld a bio-compatible matrix and support incoming cellular growth. The decellyularized dermis retains its growth factors, native collagen scaffold, and elastin, thanks to a LifeNet Health proprietaryprocessin technology.

In Silico Inhibition of Essential Candida albicans Proteins by Arenicin, a Marine Antifungal Peptide

Fungal infections increased substantially in the last years, becoming a relevant public health problem. Many of these infections account for high rates of morbidity and mortality. The emergence of resistant fungal clinical isolates have also motivate studies to find new antifungal therapies. Candida albicans is an oportunistic pathogen and affects a great number of immunocompromised patients worldwide. The marine ecosystem has been considered a rich source of bioactive metabolites due to the complexity and originality of its structures. Proteins and peptides from marine organisms have been shown to have antiviral, anti-inflammatory, antimalarial, anticancer, antimicrobial and antifungal properties. Arenicins are antimicrobial peptides isolated from the marine lugworm Arenicola marina with 21 amino acid residues in a β-hairpin structure. Dihydrofolate reductase, exo-b-(1,3)-glucanase and sterol 14α-demethylase are essential C. albincas enzymes that take part in DNA, cell wall and membrane metabolism, respectively. The present study evaluates the interaction of arenicin with important enzymes of C. albicans related to cell wall, ergosterol and DNA metabolism in order to elucidate possible molecular targets. We showed through an in silico approach, that a single compound from a marine worm (A. marina), can bind to three C. albicans essential proteins. The interaction occurs in regions inside the active site or at least near, with amino acid residues evaluated as hot spots. Arenicin is a new promising antifugal drug. The next step is to investigate protein-protein interactions performed by DHFR, EBG and CYP51 and assess whether arenicin is able to disrupt essential interaction or not.

Treatment of a Severe Pediatric Lyell Syndrome with Amniotic Membrane: Case Report and Histological Findings

Background: Lyell Syndrome (TEN, Toxic epidermal necrolysis) represents a medical emergency particularly in pediatric patients in whom the massive skin damage can quickly lead to multi-organ dysfunction and death. Prompt restoration of the physiologic mucosal/cutaneous barrier is mandatory. The use of amniotic membranes has been described in the treatment of ophthalmic Lyell Syndrome, but its use has not yet been adopted for the management of larger cutaneous wounds. Study Hypothesis: Here we report the use of amniotic membranes in a pediatric case of severe Lyell Syndrome with complete skin surface, ocular and mucosal involvement with life threating presentation. Methods: A 7-year old female was admitted to our Burn Centre for severe cutaneous/mucosal exfoliation (100% Total body surface area, TBSA) as a result of an adverse reaction to ibuprofen administration. Supportive fluid administration, cardiac-pulmonary assistance and pain management were complemented by serial grafting of amniotic membranes on all affected areas to provide coverage of the exfoliated skin/mucosa. Biopsies were obtained to monitor histological skin changes. Results: The patient showed an excellent response to amniotic membrane treatment, with rapid restoration of mucosal and cutaneous layers in the grafted areas. This resulted in a decreased need for dressing changes, avoidance of additional surgeries and a reduced dependence on supportive therapy. Lower pain levels than usually expected led to a reduced need for narcotic pain medications and allowed for early physical rehabilitation and a short hospital stay. Histology confirmed evidence of topical immune-modulation in treated areas (reduction of inflammatory infiltrate). Conclusion: As we tested in numerously TEN and burn pediatric injuries Amniotic membranes with their regenerative and immune-modulatory effects may represent an life saving treatment even in the worst cases of pediatric Lyell syndrome.

In Vitro Assessment of Estrogenic Potential of Biofield Energy Treatment using Human Endometrial Adenocarcinoma Cell Line

The objective of the study was to investigate the effect of Consciousness Energy Healing based DMEM medium on the level of alkaline phosphatase enzyme (ALP) activity in Ishikawa cells. The test item, DMEM medium was divided into two parts. One part of the test item received Consciousness Energy Healing Treatment by a renowned Biofield Energy Healer, Mahendra Kumar Trivedi and was labeled as the Biofield Energy Treated DMEM, while the other part did not receive any treatment, and defined as the untreated DMEM group. The cell viability using MTT assay of the Biofield Energy Treated DMEM group was observed as 108%, which indicated that the test item was safe and non-toxic. The estrogenic potential using ALP level showed a significantly increase by 73.21% in the Biofield Energy Treated DMEM group as compared to the untreated DMEM group. Overall, the experimental data suggested that the Biofield Energy Treated DMEM has significantly improved ALP level, which play a vital role for the promotion and maintenance of estrogen level. Based on the study outcomes, it is concluded that Biofield Energy Healing Treatment showed a significant improved ALP level, which can be used in various estrogenic disorders such as hypophosphatasia, osteoporosis, severe anemia, malnutrition, hypothyroidism, magnesium deficiency, heart surgery, aplastic anemia, chronic myelogenous leukemia, enteritis in children, Wilson’s disease, pernicious anemia, bacterial infection and intrauterine infection is a leading cause of pelvic inflammatory disease, subfertility, infertility, endometritis, early pregnancy loss, fetal defects, and preterm birth.

Effect of Bone Marrow and Adipose Mesenchymal Stem Cells on Rat Intestinal Injury Induced by Methotrexate

Methotrexate (MTX) is an anti-metabolite in cancer chemotherapy and is associated with various toxicities assigned to inflammation and oxidative stress. The present study was undertaken to corroborate the therapeutic effects of bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived mesenchymal stem cells (AD-MSCs) in MTX-induced intestinal toxicity in experimental animals as compared with dexamethasone (Dex). Rats were divided into five groups: I-Normal control group, II- MTX (14 mg/kg, as a single dose/week for 2 weeks), III & IV- BM-MSCs & AD-MSCs (2 × 106 cells/rat, 1 week after last dose of MTX), respectively, plus V- Dex (0.5 mg/kg/ for 7 days, 1 week after last dose of MTX). MTX induced marked intestinal elevation of interleukin-6, total oxidant, and nitrite/ nitrate, caspase-3 contents and myeloperoxidase activity, along with the reduction of reduced glutathione content and catalase activity. In conclusion, the positive modulation of MTX toxicity could be attributed to the free radical scavenging, anti-inflammatory and antiapoptotic potential of BM-MSC and AD-MSCs which will possibly make them as remarkable hopeful for the treatment of intestinal injury.

Antioxidative Potential of Consciousness Energy Healing Treatment on HepG2 Cells and DMEM after Oxidative Stress Induced by Hydrogen Peroxide

Antioxidants can reduce oxidative stress in cells is used for the treatment of several disorders such as cancer, cardiovascular, and inflammatory diseases. The present study was evaluated the antioxidant potential of the Consciousness Energy Healing (The Trivedi Effect®) Treated human hepatoma cell line (HepG2) and Dulbecco's Modified Eagle Medium (DMEM) for the assessment of cell viability under hydrogen peroxide-induced oxidative stress. The Biofield Energy Treated HepG2 cells group was maintained for 23 days under standard conditions. On the next day, the cells were challenged with 1 mM of H2O2 for the generation of oxidative stress. The ability of the Biofield Energy Healing Treatment to protect from the oxidative stress was determined by MTT cell viability assay and compared with the negative control group. The percentage of cell viability was significantly (p≤0.001) increased by 13.6% in the Biofield Energy Treated DMEM group; while altered by 3.2% in the Biofield Energy Treated HepG2 cells group compared to the negative control groussp. Overall, the Biofield Energy Treated DMEM showed a better antioxidative protection against oxidative stress than HepG2 cells group, which was induced by H2O2. Therefore, the results envisaged that The Trivedi Effect®- Biofield Energy Healing Treatment has an impact on the protection of various vital organs from oxidative stress; which might be helpful in the development of powerful/energized growth medium for the accelerated study with a cost-effective manner.

Clinical Evaluation of Significance of 25(Oh)D Levels in Patients with Organophosphorus Poisoning

Introduction: Organophosphate (OP) pesticide poisoning is a major challenging public-health problem in developing countries. Vitamin D deficiency is pandemic, yet it is the most under-diagnosed and under-treated nutritional deficiency in the world and it has been reported to be clinically correlated with psychiatric illness and manifestation of severe systemic inflammatory response syndrome like ARDS. Thus vitamin D deficiency may affect clinical course and outcome in cases of OPP. Aim: To evaluate status of 25 hydroxyvitamin D (25(OH)D) level in OP poisoning and its correlation with outcome of such patients. Materials and Methods: Serum 25(OH)D levels were measured at the time of hospitalization by electro-chemiluminescent Assay in 96 patients (76 male and 20 female) suffering from OP poisoning. Diagnosis of OP poisoning was made by history of poisoning including container of the poison brought by patient’s relative, clinical examination and measurement of serum butyrylcholinesterase activity. All patients were evaluated as per Performa and follow up till discharge. Results: Mean level of 25(OH)D in our cases was 24.57±9.91ng/ml and 66.7% had low levels of 25(OH)D. Our study shows linear relationship between 25(OH)D level and duration of hospital stay. All cases of OP poisoning who developed severe manifestations like ARDS, Intermediate syndrome (IMS) were having significant 25(OH)D deficiency. Our study also shows lower levels of 25(OH)D were associated with poor outcome (11.27±3.21vs 27.02±8.54, p<0.001). Conclusion: Vitamin D deficiency in OP poisoning is associated with longer hospital stay, more requirement of ventilator support and high prevalence of complication (ARDS and IMS) and poor outcome. Awareness of 25(OH)D level in patients with OP poisoning may be important to improve outcome.

Autoimmune Diseases: Genes, Inflammation And Environment

A concise review of autoimmune disease etiology emphasizes genetic susceptibility, inflammatory pathways, and environmental exposures. It points to systems approaches for risk stratification and prevention with illustrative examples.

Bone Tissue Repair During Implantation of Titanium Nickelide Mesh: Scanning Electron Microscopy and X-Ray Electron Probe Microanalysis Observation

Purpose of Study: To study reparative osteogenesis and tissue integration characteristics for implanting three-dimensional mesh structures of titanium nickelide into a bone cavitary defect. Material and Methods: The authors modeled cavitary defects of femoral metaphysis experimentally in Wistar rats divided into an experimental group and control one. The study duration was 60 days in total. The methods of radiography, those of light and electron microscopy, X-ray electron probe microanalysis used. Results: Under implantation the defect was filled with cancellous bone the volumetric density of which more than 1,5-fold exceeded control values (р < 0.001). The implant had biocompatibility, osteoconductive and osteoinductive properties, it stopped inflammatory processes. The membrane protective barrier which prevented connective tissue sprouting was formed on the implant surface in the defect periosteal zone. The osteointegrative junction was formed being persisted up to the end of the experiment. Reparative osteogenesis was performed by direct intramembranous and apposition type. Conclusion: The implant of three-dimensional mesh titanium-nickelide structures has marked osteoplastic properties, and it can be successfully used in orthopedic surgery.

Lipopolysaccharide Prompts Oxidative Stress and Apoptosis in Rats’ Testicular Tissue

Lipopolysaccharide (LPS) is a component of the outer membrane of gram negative bacteria. LPS challenging allows switching transcription of proinflammatory cytokines on via over stimulation of Toll-like receptors (TLRs) signaling pathway with subsequent pathogenic inflammatory response. We investigated the possible reproductive toxicity of LPS in male Wister albino rats. Oxidative stress markers, antioxidant status and caspase-3 activity were analyzed in testicular tissues of rats exposed to either saline or LPS (4 mg/kg BW, ip; 0.18 of the LD50). The samples were collected at 6 h and 72 h after injection of LPS. A significant reduction in testicular reduced glutathione (GSH), glutathione-S-transferase (GST) and superoxide dismutase (SOD) was observed at 72 h compared to control group. Total antioxidant capacity was decreased at 6 h with additional significant reduction at 72 h. Catalase activity was reduced significantly at both 6 and 72 h. Malondialdehyde (MDA) was increased (P ≤ 0.05) in LPS injected rats without variation between 6 and 72 h. A significant increase in nitric oxide (NO) was observed at 72 h after injection. A time-dependent increase in LPS-treated groups was observed in the concentration of caspase-3.Histopathological analysis revealed degenerative changes and necrosis of seminiferous tubules after 6 h with further accumulation of eosinophilic edematous transudate in its lumen after 72 h. In conclusion, by increasing time of exposure, LPS induced lipid peroxidation, oxidative stress, reduced testicular antioxidant capacity and encouraged testicular apoptosis which could be possible mechanisms for impairment of testicular function.

Hepatic Tuberculosis of Pseudotumor Form

Tuberculosis involving the liver in the absence of active pulmonary tuberculosis is very rare. The inflammatory pseudotumoral form is an entity difficult to diagnose. We report a case of an inflammatory pseudotumor of the liver due to tuberculosis, who didn’t underwent hepatectomy because of the size of the tumor. The diagnosis of tuberculosis was made on biopsy and Polymerase Chain Reaction (PCR).

Experimental-Morphological Study of Reparative Bone Formation with The Replacement of The Cavity Defect of The Bone with A Mesh of Titanium Nickelide

Purpose of Study To study reparative osteogenesis and tissue integration characteristics for implanting three-dimensional mesh structures of titanium nickelide into a bone cavitary defect. Material and Methods The authors modeled cavitary defects of femoral metaphysis experimentally in Wistar rats divided into an experimental group and control one. The study duration was 60 days in total. The methods of radiography, those of light and electron microscopy, X-ray electron probe microanalysis used. Results Under implantation the defect was filled with cancellous bone the volumetric density of which more than 1,5-fold exceeded control values (р < 0.001). The implant had biocompatibility, osteoconductive and osteoinductive properties, it stopped inflammatory processes. The membrane protective barrier which prevented connective tissue sprouting was formed on the implant surface in the defect periosteal zone. The osteointegrative junction was formed being persisted up to the end of the experiment. Reparative osteogenesis was performed by direct intramembranous and apposition type. Conclusion The implant of three-dimensional mesh titaium-nickelide structures has marked osteoplastic properties, and it can be successfully used in orthopedic surgery.

A Study on Contagious Bovine Pleuropneumonia in Khartoum State, Sudan

The study was carried out to investigate the occurrence of contagious bovine pleuropneumonia CBPP in Khartoum state. One-hundred twenty-two pneumonic lung tissue samples were collected from different slaughterhouses (116 samples most of which from local breed cattle) and from the field (six samples from cross breed cattle). Two-hundred and fifty-seven serum samples were collected randomly from cattle in different areas of the state. Tissue samples were cultivated using the standard mycoplasma procedures. Mmm was isolated from three pneumonic lungs collected from the field while no isolates were recovered from slaughterhouse samples. Histopathological sections from the positive samples revealed the typical picture of the CBPP which include fibrinonecrotic pneumonia within filtration of inflammatory cells and fibrin and distention of interlobular septae. One hundred and eight out of 257 serum samples were found positive for antibodies against Mmmusing complement fixation test (CFT). Findings of this study confirmed the presence of CBPP in Khartoum state by the isolation and identification of the causative agent.

Recurrent branch retinal arterial occlusions associated with plasminogen activator inhibitor-1 mutation

A 57-year-old Hispanic female presented with 3 days of blurry vision in the left eye. Eight years prior, she had a branch retinal artery occlusion in the right eye and a hematologic work-up revealed a 4G/4G polymorphism in plasminogen activator inhibitor-1. With the current episode, she was found to have bilateral branch retinal artery occlusions and mild vitritis in the left eye, simulating a toxoplasma infection. An infectious and inflammatory work up, however, was negative and the vitritis resolved after a short course of steroids. Plasminogen activator inhibitor-1 mutations may be associated with an increased risk of retinal vascular occlusions.

Juvenile Idiopathic Arthritis in a New Rheumatology Clinic in Nigeria

Objectives: To describe the frequency, clinico-laboratory characteristics and treatment outcomes of patients with juvenile idiopathic arthritis (JIA) in Lagos State University Teaching Hospital (LASUTH), Lagos, Nigeria. Methods: This is a retrospective review of patients with JIA seen over a five-year period at the rheumatology clinic and children ward of LASUTH. We reviewed the folders of 28 patients from our unit records. The demographics, baseline clinical and laboratory characteristics, treatment given and patient outcomes were extracted and analyzed. Results: A total of 28 patients with JIA were managed over the study period. Twenty one (75%) patients among our JIA cases were female and the mean age at presentation was 9.8±3.9 years. The mean duration of symptoms before diagnosis was 21.8±5.7 months. Polyarticular JIA (PJIA) constituted 14 (50%) cases, while oligoarticular and systemic-onset JIA (SoJIA) constituted 9 (39.3%) and 5 (17.9%) of the JIA cases respectively. Anaemia was present in 20 (71.4%) patients, leucocytosis in 16 (57.1%) and thrombocytosis in 11 (39.2%). Twenty five (89.2%) patients had elevated erythrocyte sedimentation rates (ESRs), 21 (75%) had elevated C-reactive protein levels and 23 (82.1%) patients had hyperferritinaemia. Positive antinuclear antibody (ANA) was found in 5 (17.8%) patients. Mortality was documented in 2 (7.1%) patients both of whom were SoJIA cases. Eleven (39.3%) patients were lost to follow up. Conclusion: Unlike the common report of oligoarticular JIA (OJIA) being the most frequent subtype of JIA in various series from North America and Europe, PJIA was the most frequent subtype seen among our patients and this variant accounted for half of all JIA cases seen. There were no cases of psoriatic, enthesitis-related or undifferentiated JIA and most patients had haematological abnormalities and high levels of inflammatory markers at presentation.

A Model for Identifying Actionable Findings on Computed Tomography in Crohn’s Disease Patients in the Emergency Department

Patients with inflammatory bowel disease (IBD) frequently visit the emergency department (ED). The use of cputed tomography (CT) scans in this population has drastically increased in recent years and may confer an increased risk of malignancy. Records were obtained for IBD patients aged 18 or older who visited our institutional ED with a gastrointestinal chief complaint and who had a CT scan ordered by an ED physician. A predictive model for identifying a clinically actionable finding (CAF) on CT scan was created using logistic regression carried out on a predetermined set of variables. Data were available on 156 Crohn’s disease (CD) patients contributing 350 visits and 63 ulcerative colitis (UC) patients contributing 114 total visits. CAF was identified at 108/350 (30.9%) of visits in CD patients and 33/114 (29.0%) of visits in UC patients. History of CAF (OR 11.6, CI 4.54-29.6) and a platelet count above 400,000/mL (OR 3.42, CI 1.56-7.50) were the strongest predictors of CAF. History of psychiatric illness (OR 0.67, CI 0.35-1.29) and diarrhea (OR .043, CI 0.23-0.83) were associated with a lower likelihood of CAF. A prediction model was created that was able to detect 94.4% of CAF cases while correctly predicting CAF non-cases 35% of the time. This model holds promise as a tool to reduce imaging in this population.

Vitamin D Status in Diabetes Mellitus: Comparison Between Outpatients and Inpatients

Objectives: Vitamin D (25(OH)D) status has been extensively evaluated in different populations and care settings. A negative relationship between glycated hemoglobin (HbA1c) and serum 25(OH)D levels in outpatients with diabetes has been reported, while data about 25(OH)D status in inpatients with diabetes are inconsistent. The aim of the study was to evaluate 25(OH)D levels in a large series of inpatients with type 1 and type 2 diabetes and in an age-, sex-, serum creatinine-, and HbA1c-matched group of outpatients with diabetes. Design: After the preliminary exclusion of patients with confounding factors, 540 subjects with diabetes were retrospectively evaluated in a 1:1 matched case-control study between inpatients and outpatients. Results: 25(OH)D levels resulted significantly lower in inpatients versus outpatients with diabetes (37.9 nmol/L, median, 25.3 interquartile range, vs 44.9, 31.8 nmol/L, respectively), regardless of season. 25(OH)D levels were inversely correlated with HbA1c levels and BMI in outpatients, and with fibrinogen and erythrocyte sedimentation rate in inpatients. Conclusions: Vitamin D deficiency is common in diabetic inpatients and more frequent than in diabetic outpatients. 25(OH)D status in diabetic inpatients is not related to glycemic control but is likely influenced by acute inflammatory condition.

Frailty and the Immune System

Frailty describes a medical syndrome that confers increased vulnerability to disproportionate changes in health status following minor stressors. With loss of homeostatic reserve in multiple physiological systems, frailty conveys an increased risk of adverse health outcomes. Despite the lack of a clear universal definition, the utilisation of two landmark operational models has allowed a rapid expansion in frailty-centred research. The pathophysiology of frailty is yet to be elucidated in the literature, but a critical role for a heightened inflammatory state is hypothesised. Raised levels of pro-inflammatory cytokines are associated with frailty, with emerging evidence relating their biochemical action with development of the frailty phenotype. Dysregulation of both the innate and adaptive immune system are key components of the frailty syndrome. Remodelling of the T cell compartment and upregulated inflammatory pathways are theorised to propagate the heightened inflammatory state critical in the frailty syndrome. Increased neutrophil counts, in conjunction with ineffective neutrophil migration associated with age, is theorised to produce tissue damage and secondary inflammation conducive of the inflammatory picture in frailty. Beyond the gold standard of the comprehensive geriatric assessment, management of frailty is a fast-evolving area of research. Exercise interventions have shown promising results, improving functional ability and showing beneficial immunomodulation. Vitamin D supplementation, with proposed anti-inflammatory effects, nutritional support and pharmacological treatments all provide promising areas for future therapeutic intervention.

Transiently Raised IOP Equivalent to That Experienced During Ocular Surgery Causes Moderate Inflammation but does not Affect Retinal Function or Result in Retinal Ganglion Cell Loss in An Animal Model

Purpose: High intraocular pressure (IOP) is known to result in retinal ganglion cell (RGC) loss, both with chronically raised intraocular pressure (such as with glaucoma) and with acute raises in pressure (due to injury or acute angle closure). Because IOP is often raised during ocular surgery, the purpose of this study was to evaluate the effect of transient moderate IOP on retinal function, RGC survival and the expression of Connexin 43 (Cx43) and glial fibrillary acidic protein (GFAP), ubiquitously expressed central nervous system (CNS) proteins that are known to be elevated during the retinal inflammatory response to injury. Materials and Methods: Wistar rats were exposed to transient IOP at 40 mmHg for 5 or 30 minutes, and 60 mmHg for 5 minutes (via cannulation of the anterior chamber with a saline reservoir raised to a height corresponding to the desired IOP), mimicking potential IOP rises during surgery such as DSAEK and some laser procedures (LASIK and femtosecond laser cataract surgery). Separate groups of animals had IOP maintained at 10 mmHg for 5 or 30 minutes as cannulation controls, or 120 mmHg for 60 minutes as positive controls. Changes in the optic nerve and retina were assessed immunohistochemically for GFAP and Cx43 expression. Retinal function was assessed using electroretinography (ERG) recorded at baseline and 14 days after the IOP rise and compared with RGC counts. Results: Results showed that there was a differential GFAP labelling pattern observed in the anterior optic nerve in the 40 mmHg 30 minute and 60 mmHg 5 minute groups 4 hours after manipulation. Gap junction protein Cx43 was minimally up-regulated in the retina in the short-term. There was, however, minimal long-term effect on retinal function and no RGC loss. Conclusions: n conclusion, elevations of IOP that are short in duration such as those occurring during surgical procedures, do not cause significant changes long-term in retinal function or RGC survival. Key Messages: Cx43 and GFAP are known to be elevated during the retinal inflammatory response to injury. No previous study has explored the effect of moderate and relatively short increases in IOP on the initial inflammatory response. We observed a mild glial inflammatory response in the anterior optic nerve, but only a minimal up-regulation of Cx43. However, transient and moderate IOP rises did not induce long term disruption to RGC function or number as measured by electrophysiology and RGC counts, respectively. This is applicable to clinical practice, as it means the IOP elevations that occur during some surgical procedures are unlikely to be causing long term damage in retinal function or RGC survival.

Combination of Radiation Therapy and Immunotherapy in the Treatment of Melanoma

Melanoma is considered to be a very aggressive cancer due to its rapid growth, early and multiple metastases and limited response to standard treatment. Many researchers have hypothesized that the combination of radiation therapy and immunotherapy in the treatment of melanoma primary tumors and metastases improves the efficiency of these methods as compared to their use separately. Therefore, combined therapy is an increasingly popular topic in radiation oncology. Although the mechanism of immune response to ionizing radiation remains unclear, known are the factors involved in the immune response, including NK and CD8(+) T cells. Many studies have demonstrated the importance of inflammatory factors, primarily cytokines, in the response to ionizing radiation. In turn, many cytokines released in an irradiated organ, such as tumor necrosis factor α (TNFα), interleukins IL1 and IL6 and transforming growth factor beta (TGFβ), can induce the production of significant amounts of reactive oxygen species that are associated with the induction of DNA damage in tumor cells. In relation to anticancer immunotherapy, the clinical data obtained to date can encourage future studies combining radiation therapy and the inhibitors of cell division checkpoints in the treatment of advanced melanoma. In a recent study, melanoma cell lines became more sensitive to radiation after BRAF inhibition, which provides a potential synergistic mechanism of BRAF inhibitor (BRAFi) combined with radiation therapy for better effects of treatment.  In this article, we present a systematic review of the literature on the use of the combination of radiation therapy and immunotherapy in the treatment of melanoma.

A Bit Exagerrated Role of Complete Blood Count Parameters on the Prognosis of Idiopathic Sudden Sensorineural Hearing Loss

Idiopathic sudden sensorineural hearing loss (ISSHL) is a commonly seen otorhinolaryngology emergency, and its etiology is still a mystery. In this retrospective clinical study, we aimed to investigate the possible relationship of inflammatory markers derived from CBC such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), Red cell distribution width-to-platelet ratio (RPR), lymphocyte-to-monocyte ratio (LMR), mean platelet volume (MPV) and platelet distribution width (PDW) in ISSHL . A total of 50 idiopathic sudden hearing loss patients were included in the study. They were grouped according to their hearing healing levels as recovered, partially recovered and unrecovered. Also 47 age- and sex- matched healthy individuals created the control group. Their complete blood count parameters of NLR, LMR, PLR, RPR, PDW and MPV were recorded. The results were statistically compared to bring out a significant difference between the groups. There was no significant demographic difference between the groups. The comparison of patient  group with control group reveal a significant difference in the NLR, LMR and PDW values (p<0.05). The remaining values were not statistically significant.  The analysis of these values according to the recovery level of the ISSHL, there was no statistical difference between the groups (p>0.05). We demonstrated for the first time that LMR value was significantly elevated in ISSHL patients. NLR, LMR, and PDW might be indicative for diagnosis of ISSHL. However, we believe that using these parameters for the screening of the prognosis is a clinically useless exercise.

Breast Feeding and Melatonin: Implications for Improving Perinatal Health

The biological underpinnings that drive the plethora of breastfeeding benefits over formula-feeding is an area of intense research, given the cognitive and emotional benefits as well as the offsetting of many childhood- and adult-onset medical conditions that breast-feeding provides. In this article, we review the research on the role of melatonin in driving some of these breastfeeding benefits. Melatonin is a powerful antioxidant, anti-inflammatory and antinociceptive as well as optimizing mitochondrial function. Melatonin is produced by the placenta and, upon parturition, maternal melatonin is passed to the infant upon breastfeeding with higher levels in night-time breast milk. As such, some of the benefits of breastfeeding may be mediated by the higher levels of maternal circulating night-time melatonin, allowing for circadian and antioxidant effects, as well as promoting the immune and mitochondrial regulatory aspects of melatonin; these actions may positively modulate infant development. Herein, it is proposed that some of the benefits of breastfeeding may be mediated by melatonin's regulation of the infant's gut microbiota and immune responses. As such, melatonin is likely to contribute to the early developmental processes that affect the susceptibility to a range of adult onset conditions. Early research on animal models has shown promising results for the regulatory role of melatonin.

Changes in Gingival Crevicular Fluid Volume and Flow Rate During Orthodontic Treatment

Background: Gingival crevicular fluid (GCF) is regarded as a promising medium for detection of periodontal disease activity. bone loss is a major feature of periodontal disease, although we are unable to determine the time of this bone loss and therefore periodontal disease activity. During orthodontic treatment small forces are applied, resulting in bone remodeling which allows tooth movement. Orthodontic model may be used as a preliminary stage in evaluating gingival crevicular fluid role in bone turnover. Aims: To detect GCF and to monitor it's volume and flow rate following orthodontic activation, and to determine at what stage inflammation and bone resorption reach their maximum. Materials and Methods: GCF samples were collected from 10 adult orthodontic patients (mean age = 22.3 , range 20-24year) on 3,7,10,14,21,28,35 days after activation of orthodontic appliance, from the tooth surface where bone resorption was expected to occur. A total of 330 GCF sample were collected using filter paper strip, the volume measured by weighing. Results: An insignificant increase in GCF volume and flow rate was noted in the tenth day after activation of the orthodontic appliance activation. At 35 days GCF reached its minimum flow rate. There was considerable variation between subjects and between the same subject on different days Conclusion: Increase in GCF volume and flow rate reflects the effect of orthodontic adjustment rather than oral hygiene, as there were no clinical inflammatory changes during the period of orthodontic treatment studied.

Low Laser Therapy Plus Non-Surgical Periodontal Treatment Reduces Interleukin-1 Beta Serum Levels

Objectives: Periodontal disease is associated to widespread systemic inflammation, and further to both cardiovascular morbidity and mortality. Data from intervention studies demonstrated the beneficial effects of periodontal therapy in reducing vascular diseases. The present study was aimed to explore whether low-level Laser therapy as an adjunct to scaling and root planning reduces serum levels of inflammatory cytokines. Material and Methods: Thirty patients were enrolled. All recruited participants underwent blood sampling and dental inspection for periodontal indexes measurement. Plaque index, gingival index and probing depth were employed as measures of periodontal disease. Afterwards, patients underwent scaling and root planning plus low-level Laser therapy. Inflammatory biomarkers and periodontal indexes were measured before treatment and twenty weeks after treatment. Results: Plaque index, gingival index and probing depth largely improved at the follow-up visit, resulting more than halved from the baseline. Furthermore, a significant reduction of serum interleukin-1 beta has been observed (1.1 SD 2.1 vs 0.5 SD 1.3, P = 0.04), whereas serum interleukin-6 levels remained substantially unchanged. Blood C-reactive protein levels decreased at the follow-up, but not reaching statistical significance. Conclusions: therapy addressed to a local improvement of periodontal disease gives a reduction of systemic inflammation, possibly beneficial for cardiovascular health.

A Case of Pernio Associated with Cold Agglutinin Positivity in an Unusual Location

Pernio is an inflammatory disease that is usually characterized by the development of cold-induced erythrocyanotic skin lesions located in acral regions. Diagnosis is difficult if lesions are present in rare locations. A 21-year-old female suffering from fatigue presented with a 4-day history of painful, purple lesions on both thighs. She worked as a cashier, wore tight clothing, and was otherwise healthy except for mild obesity. Dermatological examination revealed tender and painful edematous papules and plaques on the outer aspects of her thighs. The patient was diagnosed with pernio based on her medical history, and clinical and histological findings. Laboratory tests were normal except for her cold agglutinin titer (1:4). Pernio rarely occurs on the thigh, except in people who ride horses. However, it sometimes occurs in non-riders depending on lifestyle and environmental conditions. Therefore, lesions in this region must be confirmed by a thorough medical history and evaluation of clinical and histopathological findings. Cold agglutinins may be associated with this disease.

The Role of BCL-2 and BAK Genes in Chronic Kidney Disease and Haemodialysis Patients

Background: Polymorphonuclear leucocytes are the first line of defence against foreign invaders and constitute the major cell type involved in certain types of acute and chronic inflammatory diseases. Aim of the Work: The aim of the present study was to investigate the changes in expression of BCL-2 and BAK genes by real time PCR and to study whether they were involved in the accelerated neutrophil apoptosis which might be responsible for the recurrent bacterial infections seen in chronic renal disease and hemodialysis patients. Subjects and Methods: This study was conducted on sixty two subjects. Patients were selected from those admitted to Theodor Bilharz Research Institute (TBRI). Patients under study were classified into three groups; CKD patients (group I) kept on conservative treatment (22 cases), ESRD patients (group II) maintained on dialysis therapy, HD (20 cases). In addition, twenty healthy individuals served as a control group (group III) were involved. Results: There was significant increase in level of BAK gene in both patients' groups compared to control group with more increase in CKD group than ESRD group. Significant difference between the 3 groups was encountered with a higher expression level in CKD and ESRD groups than controls. There was decrease in level of BCL2 gene in both groups less than control group with more declines in ESRD group than CKD group. Conclusion: Bcl2 and Bak genes could have a role in survival and apoptosis of the studied groups and suggested their impact in controlling the inflammatory mechanisms and eventually their therapeutic potential.

Clinical and Immunological Beneficial Effects of Phyto V7 Consumption by HIV-1 Seropositive Individuals

Phytochemicals (PHT) are a large group of biologically active plant chemicals that may have positive effects on human health such as immune system stimulation, down regulation of inflammatory responses, radical scavenging activities, cell repair function, and antibacterial and antiviral activity. In this proof of principle 6 months study, the effects of supplementing a PHT mix, Phyto V7, to HIV-1 seropositive individuals and AIDS patients were examined. Individuals with CD4+ T-cells below 350 counts/mm3were assigned to one of the following treatments: CG1 - no treatment, CG2 - only highly active antiretroviral treatment (HAART), TG1 - only Phyto V7, and TG2- both Phyto V7 and HAART. After 3 months of treatment there were approximately (-)1%, 1%, 2% and 4% increase in the mean weight of the CG1, CG2, TG1 and TG2 groups, respectively. The tendency for the body mass index (BMI) was similar. The CD4+ counts increased by 13%, 39%, 53% and 35%, respectively. Similar trends were noted after 6 months with 2%, 79%, 53% and 69% increases in the CD4+ counts, respectively. There was a significant reduction in viremia only in groups receiving HAART. Overall better results were obtained in the group of patients receiving both HAART and Phyto V7, in which the mean weight increased by 5.7% and the CD4+ T-cell counts increased by 69% after 6 months. This study indicates that providing Phyto V7 to HIV-1 seropositive individuals and AIDS patients, receiving or not receiving HAART, improves their physical wellbeing and CD4+ counts, enabling them to cope better with the viral infection.

RETRACTED: In-Stent Thrombosis in the Middle Cerebral Artery (MCA): A Case Report

This article has been retracted on November 20, 2015. VIEW THE RETRACTION NOTICE (https://doi.org/10.14302/issn.2470-5020.jnrt-25-5846) In-stent thrombosis (IST) is a complication of angioplasty and stenting, especially in the vessels with smaller diameter. We present a case of subacute IST after stenting treatment of an isolated higher stenosis of the right middle cerebral artery (MCA). Analysis of clinical features and emergent brain image helped to indicate the pathophysiological mechanism underlining the symptoms of this patient. Emergent Transcranial Doppler (TCD) helped to evaluate the compensatory collateral circulation and provided good supporting evidence in deducing the mechanism of IST. Slightly larger size of the implanted stent that caused dissection or vascular endothelium injury was presumed in this patient. Persistent evidence of inflammatory factors might also contribute to IST in this patient.

Management of Absent Capsular Support with a new Intraocular Lens Design

Purpose: To describe a new intraocular lens that can be implanted in case of rupture of the posterior capsule and lack of capsular support. Methods: This experimental study was carried out on ten Flanders rabbits. The right eye of each rabbit underwent intra capsular lens extraction and two peripheral iridectomies, and the new lens was implanted with an optic rest in the posterior chamber. Additionally, the haptics rest in the angle of the anterior chamber through peripheral iridectomies. Main outcome measures were lens stability inside the eye and complications regarding this technique. Results: Intraocular lenses remained in a stable position with only a mild inflammatory reaction; four eyes developed hyphema that disappeared 10 days after surgery. Conclusion: The new lens design has good intraocular stability when posterior capsular support is absent and only produced minimal inflammation inside the eye.

Kynurenines and Vitamin B6: Link Between Diabetes and Depression.

The increased association between depression and diabetes mellitus is generally acknowledged. Recent studies suggest that depression leads to diabetes.However, the underlying molecular mechanisms for this association remain unclear.Literature and our data indicate that inflammatory and/or stress factors in depression up-regulate tryptophan (TRP) conversion into kynurenine (KYN), a substrate for nicotinamide adenine dinucleotide (NAD) biosynthesis. Deficiency of vitamin B6, a co-factor of the key enzymes of KYN – NAD pathway, shunts KYN metabolism from formation of NAD towards production of xanthurenic (XA) and kynurenic (KYNA) acids. Human and experimental studies reveal that XA, KYNA and their metabolites interfere with production, release and biological activity of insulin. We propose that inflammation- and/or stress-induced up-regulation of TRP – KYN metabolism in combination with vitamin B6 deficiency is one of the mechanisms mediating increased risk of diabetes in depression. Consequently, monitoring formation of diabetogenic KYN derivatives might help to identify subjects-at-risk for the development of diabetes. Pharmacological down-regulation of the TRP – KYN – NAD pathway and maintenance of adequate vitamin B6 status might help to prevent the development of diabetes in depression and other conditions associated with inflammation/stress–induced excessive production of KYN and vitamin B6 deficiency, e.g., obesity, cardiovascular diseases, aging, menopause, pregnancy, and hepatitis C virus infection.