Significant Increase In Serum Levels Research Articles

Исследование иммунопатологических процессов, связанных с развитием фиброза печени

The aim of this study was to determine the dependence of the course of liver fibrosis on the functional state of the immune system, in particular, on the imbalance of pro-inflammatory and anti-inflammatory immune reactions that are formed in patients during the development of the disease. The study included 30 patients with chronic liver diseases (18 patients with chronic hepatitis C (CHC) and 12 patients with alcoholic liver disease (ALD), 15 healthy individuals were the comparison group. Liver elastography (FibroScan) was used to evaluate liver stiffness and determine fibrosis stages according to METAVIR classification. The following cytokine levels were measured in the serum samples of the group: IL-1β, TNF-α, IL-6, IFN-γ, IL-2, IL-4, IL-8, VEGF and TGF-β. According to the data presented in this work, in patients with CHC and ALD, there was a statistically significant increase in serum levels of pro-inflammatory cytokines, namely: IL-1β, TNF-α, IFN-γ, IL-2, IL-6 and IL-8. Interestingly, elevated TGF-β values were found in patients with CHC, but not in patients with ALD. Significantly lower concentrations of VEGF were observed in both study groups. There was also a significant decrease in serum IL-4 in patients with CHC, whereas in patients with ALD such a decrease was not statistically significant. Serum IL-1β content was approximately equally elevated in the early and late stages of fibrosis. A sharp rise in serum TNF-α levels occurred in the early stages of fibrosis. In the later stages, the rise in the level was replaced by a sharp fall. However, the serum levels of TNF-α in the later stages of liver fibrosis still significantly exceeded control values. The serum levels of IFN-γ in patients significantly exceeded control values without changes in different stages of fibrosis. Relatively high levels of serum IL-2 and IL-6 were noted only in the later stages of the disease. In both groups of patients, a clear dependence of serum levels of IL-8 on the stage of fibrosis was revealed. Analysis of the data allows us to conclude that immune mechanisms play a significant role in the pathogenesis of degenerative liver diseases. Therefore further studies of the mechanism and role of immune factors is required to explore possible diagnostic and therapeutic applications.

Assessment of Serum Level of Interleukin-17 in Patients with Vitiligo

Vitiligo is a multifactorial disorder related to both genetic and non-genetic factors. The pathogenesis of vitiligo is associated with the melanocytes destruction that may result from immune and inflammatory mediators. The autoimmune theory is the most important theory about the pathogenesis of vitiligo. The aims of the study are the evaluation and assessment of serum levels of IL17 in vitiligo patients to reveal their possible role in pathogenesis of vitiligo and to correlate their levels with the severity of the disease. Patients and Methods: In this study, thirty patients (15 male and 15 females) were included in the present study and 30 apparently healthy, age and sex matched individuals were included as a control group. Patients were recruited from the outpatient clinic of Benha University Hospitals from Dermatology, Venereology and Andrology Department. All patients were subjected to full history, full dermatological and general examination. Measurement of serum levels of IL-17 using the commercially available ELISA kit. Results: The present study revealed significant increase in serum levels of IL-17 in patients than controls. Conclusion: Vitiligo is associated with increased serum level in IL-17 indicating that IL-17 may play a significant role in the pathogenesis of vitiligo.

A clinically relevant combination treatment of doxorubicin and cyclophosphamide does not induce hepatotoxicity in C57BL/6J mice

Chronic exposure to chemotherapeutics can lead to severe adverse events including hepatotoxicity. A combination chemotherapy regimen of doxorubicin (DOX) and cyclophosphamide (CPS) is employed in treatment of several cancers such as leukemia, lymphoma, and breast cancer. It is currently not well understood whether a combination therapy of DOX and CPS can induce hepatotoxicity. We therefore sought to determine whether co-administration of DOX and CPS at their clinically relevant doses and frequency results in hepatotoxicity. Male C57BL/6J mice received one intraperitoneal injection of saline or DOX-2mg /kg and CPS-50mg/kg once a week for 4 weeks. After the treatment period, liver histology and various serum biomarkers of hepatotoxicity were assessed. Co-treatment of DOX and CPS did not alter the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, albumin, globulin, or total protein. Similarly, co-administration of DOX and CPS did not result in a noticeable change in liver histology. However, it was notable that the concomitant treatment with DOX and CPS resulted in a significant increase in serum levels of aspartate aminotransferase (AST). Elevated serum AST levels were also associated with increased serum creatinine kinase (CK) levels, suggesting that the elevated serum AST levels are likely due to muscle injury following the co-administration of DOX and CPS. Taken together, our results, for the first time, suggest that co-administration of DOX and CPS, at their clinically relevant doses and frequency, does not induce a significant hepatotoxicity in the mice.

EFFECT OF DIETARY ROCKET SEEDS MEAL AND NANO-CHITOSAN ON PERFORMANCE AND RELATED GENE EXPRESSION TO GROWTH AND LIPID PROFILE IN BROILER CHICKS

This study was carried out to evaluate the impacts of inclusion of two plant proteins (soybean meal or rocket meal) in the starter and growing –finishing diets fed with / without nano-chitosan for 500 one-day old broiler chicks on growth performance and serum parameters as well as expression patterns of target genes (PPARα,PPARγ and IGF-1) in liver tissue. A total of 220 chicks were randomly distributed into four treatment (five replications, each), and housed in a floor pen under hygienic conditions. The results indicated that birds fed 7.5% rocket seed meal (RSM) exhibited the best means of FBW, BWG and FCR. While, least feed intake with higher FBW and BWG was found in nano-chitosan fed birds. RSM fed chicks had a significant decrease in serum levels of TG, LDL, total lipids, AST and ALT with insignificant changes in serum albumin, total Cholesterol and HDL compared with the control group. Furthermore, significant increases in serum levels of IgG, IgM, IgA, CAT, TAC, SOD, T3, T4 and FSH were found in RSM fed birds as compared to the control group. Insignificant differences were noted in the fold changes of gene expression among the different experimental groups of chicks with regard toIGF-I and PPARα genes, but the RSM-diet insignificantly increased in the transcript level of the IGF-I gene and improved the IGF-1 gene expression. Our findings declared that RSM can be used in chicks diet up to 7.5 % singly or in combination with nano-chitosan without any adverse effect on performance, blood parameters and related gene expression in broiler chicks.

Estimation Of Plasminogen Activator Inhibitor -1 And Some Biochemical Markers In A Sample Of Iraqi Patients With Liver Cirrhosis

Objective: The aim of present study was designed to estimate level of plasminogen activator inhibitor -1 in liver cirrhotic patients, and its correlation with some biomarkers includes ( Liver enzymes: ALT,AST and Bilirubin ,Total protein, albumin. Methods: The current study include 30 Iraqi liver cirrhotic patients with age range 25-65 years and 30 healthy control subjects with age range 25-60 years. Results: The present study had been shown a high significant differences in liver enzymes ALT, AST and ALP when compare with control p≤ 0.01, 0.05 and 0.01 respectively. The difference in the mean serum level of albumin and total bilirubin were also observed to be highly significant in the liver cirrhosis patients p ≤ 0.01. Concerning mean serum level of PAI-1 in the liver cirrhosis patients a significant deference was found when compared to control with p≤0.05. Also there were a non-significant correlation between age and studied parameters Conclusions: The results of the present study showed a significant increase in serum levels of PAI-1 ALT,AST,ALP,T Bilirubin ,and Albumin while a non-significant differences in these parameters was shown in relation to age and gender.

Ameliorative effects of garlic oil on FNDC5 and irisin sensitivity in liver of streptozotocin-induced diabetic rats.

This study was aimed to investigate the effects of garlic oil (GO), an important natural constituent used in alleviating diabetes and its complications, on the expression levels of irisin and related genes. Thirty-two rats were divided into four groups: Control, Diabetes-Control, Diabetes+GO 100 mg/kg/day and Control+GO 100 mg/kg/day for 45 days. The measurements included: changes in liver Peroxisome proliferator-activated receptor-gamma-coactivator (PGC)-1α, Fibronectin Type-III-Domain-Containing5 (FNDC5), irisin expression, mRNA expression of p38 and TNF-α (Tumour necrosis factor-α), total-antioxidant-status (L-TAS; S-TAS), total-oxidant-status (L-TOS; S-TOS) in liver and serum, respectively. There was a significant reduction in serum levels of irisin and S-TAS and expression of PGC-1α and FNDC5 in liver in Diabetes-control compared to Control-group, while a significant increase in serum levels of fasting blood glucose (FBG) and TOS, also p38 and TNF-α expressions in liver. In Diabetes+GO group, there was a significant increase in serum irisin and S-TAS, also expression of PGC-1α and FNDC5 in liver, while serum FBG, S-TOS levels, and mRNA expression of p38 and TNF-α in liver were decreased compared to Diabetes-control group (P < 0.05). GO alleviated the diabetic liver injury by decreasing Oxidative-Stress parameters and regulation PGC-lα, FNDC5, irisin and P38, keeping the balance of TAS/TOS and TNF-α.

Temporal Dynamics of Chronic Inflammation on the Cecal Microbiota in IL-10-/- Mice.

The intestinal microbiota is a critical component of mucosal health as evidenced by the fact that alterations in the taxonomic composition of the gastrointestinal microbiota are associated with inflammatory bowel diseases. To better understand how the progression of inflammation impacts the composition of the gastrointestinal microbiota, we used culture independent taxonomic profiling to identify temporal changes in the cecal microbiota of C3Bir IL-10-/- mice concomitantly with the onset and progression of colitis. This analysis revealed that IL-10-/- mice displayed a biphasic progression in disease severity, as evidenced by histopathological scores and cytokine production. Beginning at 4 weeks of age, pro-inflammatory cytokines including TNF-α, IFN-γ, IL-6, G-CSF, and IL-1α as well as chemokines including RANTES and MIP-1α were elevated in the serum of IL-10-/- mice. By 19 weeks of age, the mice developed clinical signs of disease as evidenced by weight loss, which was accompanied by a significant increase in serum levels of KC and IL-17. While the overall diversity of the microbiota of both wild type and IL-10-/- were similar in young mice, the latter failed to increase in complexity as the mice matured and experienced changes in abundance of specific bacterial taxa that are associated with inflammatory bowel disease in humans. Collectively, these results reveal that there is a critical time in young mice between four to six weeks of age when inflammation and the associated immune responses adversely affect maturation of the microbiota.

Vitexin prevents colitis-associated carcinogenesis in mice through regulating macrophage polarization

BackgroundPatients with inflammatory bowel disease are at increased risks of developing ulcerative colitis-associated colorectal cancer (CAC). Vitexin can suppress the proliferation of colorectal carcinoma cells in vitro orin vivo. However, different from colorectal carcinoma, CAC is more consistent with the transformation from inflammation to cancer in clinical chronic IBD patients. Therefore, we aim to investigated that vitexin whether possess benefic effects on CAC mice. PurposeWe aimed to determine the beneficial effects of vitexin on CAC mice and reveal its underlying mechanism. MethodsThe mouse CAC model was induced by Azoxymethane and dextran sodium sulfate (AOM/DSS) and CAC mice were treated with vitexin. At the end of this study, inflammatory cytokines of IL-1β, IL-6, TNF-α, IL-10 as well as nitric oxide (NO) were detected by kits after long-term treatment of vitexin. Pathological changes and macrophage polarization were determined by H&E and immunofluorescence in adjacent noncancerous tissue and carcinomatous tissue respectively of CAC mice. ResultsOur results showed that oral administration of vitexin could significantly improve the clinical signs and symptoms of chronic colitis, relieve colon damage, regulate colonic inflammatory cytokines, as well as suppress tumor incidence and tumor burden. Interesting, vitexin caused a significant increase in serum level of NO and a higher content of NO in tumor tissue. In addition, vitexin significantly decreased M1 phenotype macrophages in the adjacent noncancerous tissue, while markedly up-regulated M1 macrophage polarization in the tumor tissue in the colon of CAC mice. ConclusionVitexin can attenuate chronic colitis-associated carcinogenesis induced by AOM/DSS in mice and its protective effects are partly associated with its alternations in macrophage polarization in the inflammatory and tumor microenvironment .

Effect of Fasting-Mimicking Diet or Continuous Energy Restriction on Weight Loss, Body Composition, and Appetite-Regulating Hormones Among Metabolically Healthy Women with Obesity: a Randomized Controlled, Parallel Trial.

Fasting-mimicking diet (FMD) has been recently promoted to achieve similar metabolic changes of fasting. The purpose of our study was to compare the effect of FMD versus continuous energy restriction (CER) on anthropometric measurements, body composition, glucose metabolism, and serum levels of leptin, neuropeptide Y (NPY), and total ghrelin. A randomized controlled trial (RCT) was conducted on 60 women with obesity aged 18-55years. Subjects received either a 5-day FMD (low in energy, sugars, and proteins, but high in unsaturated fats) or a CER (an average daily energy deficit of 500kcal) for 2months. Anthropometric and biochemical factors were measured at baseline and the end of the study. Serum levels of leptin, total ghrelin, and NPY were tested with an ELISA kit. Physical activity and dietary intakes were also recorded. There was no significant difference in weight loss between the two groups: mean weight change for CER was - 2.29 (standard deviation [SD], 1.95) kg compared to - 1.13 (2.27) kg for FMD (p = 0.06). There was more reduction in the basal metabolic rate (BMR) in the CER group (p = 0.045). Favorable effects on fat mass and muscle mass were only seen in the FMD group. Although insulin resistance was reduced in the FMD group compared to the CER group, results were not significant after adjustment. After controlling for potential confounders, there was a significant increase in serum levels of total ghrelin (p = 0.048) and NPY (p = 0.041) following CER; however, results for circulating leptin were not statistically significant (p = 0.48). There was no significant difference in weight loss following FMD and CER. However, FMD was more effective at reducing insulin resistance and regulating appetite-regulating hormones as well as preserving muscle mass and BMR. This trial was registered at the Iranian Clinical Trial Registry ( https://www.irct.ir/trial/40881 ) with the IRCT identification number IRCT20190717044244N1.

Prognostic markers for severity, activity, and recurrence of alopecia areata

Background Alopecia areata (AA) is considered an autoimmune disorder caused by altered T-cell-mediated immunity. MicroRNAs (miR) are important translational regulators of genes in various tissues and biological processes involved in autoimmune responses and have been identified in autoimmune diseases such as rheumatoid arthritis and type I diabetes mellitus. However, little is known about their role in pathogenesis of AA.Objective To assess serum levels of miR-155 and miR-146a in patients with AA and to correlate them with different clinical variables. Patients and methods MiR-155 and miR-146a serum levels were identified by real-time PCR in 50 patients with AA and 50 healthy age-matched and sex-matched patients as controls. Disease severity in the patients was assessed by Severity of Alopecia Tool score. Results There was a statistically significant increase in serum miR-155 and miR-146a levels in patients with AA than in controls. A significant increase in serum levels of miR-155 was found in patients with active disease and recurrent lesions of AA, whereas significant increase in serum level of miR-146a was found in patients with recurrent disease only. Significant positive correlations were found between serum miR-155 and miR-146a levels and disease severity. Conclusion Serum levels of miR-155 and miR-146a seem to have an essential role in the etiopathogenesis of AA and could be markers for severity and early detection of recurrent AA. In addition, serum miR-155 could be a marker of activity in AA, whereas serum miR-146a could be a marker of multiplicity. Further understanding of the function and regulation of miR-155 and miR-146a could be of great value for the introduction of new therapeutic approaches for AA.

The effects of spirulina under high-intensity interval training on levels of nesfatin-1, omentin-1, and lipid profiles in overweight and obese females: A randomized, controlled, single-blind trial.

Background: We investigated the effects of spirulina under high-intensity interval training (HIIT) on levels of nesfatin-1, omentin-1, and lipid profiles in overweight and obese females.Materials and Methods: This is a randomized, quasi-experimental controlled, single-blind with a pre- and post-test design, in which twenty overweight and obese women (body mass index = 29.32 ± 3.01 kg/m2, age = 21.55 ± 1.76 years), were randomly divided into the following groups: HIIT + spirulina (n = 10) and HIIT + placebo (n = 10). Running anaerobic sprint test was used for HIIT protocol consisting of six intervals at 35 m maximal speed runs, with a rest of 10 s in each trial (3 times/week, 4 weeks). HIIT + spirulina group received 500 mg of the spirulina pills twice daily for 4 weeks and the second group took placebo.Results: There was a significant increase in serum levels of nesfatin-1 in HIIT + spirulina (P < 0.0001) but not in HIIT + placebo (P = 0.61) group. Furthermore, results indicated a significant difference between two groups with respect to serum levels of nesfatin-1 (P = 0.04). Serum levels of omentin-1 significantly increased in both groups (P < 0.05). However, there was no significant difference between two groups (P = 0.49). In addition, results showed no significant inter- and intra-group differences in total cholesterol levels, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol between groups (P > 0.05).Conclusion: The spirulina under HIIT increased levels of nesfatin-1 and omentin-1 with no effects on the levels of lipid profiles in overweight and obese females.

Metformin reduces ovarian ischemia reperfusion injury in rats by improving oxidative/nitrosative stress

ObjectiveTo assess the preventive role of metformin on rat ovarian ischemia reperfusion injury. Materials and methodsForty rats were divided equally into five groups; Group 1: sham, Group 2: surgical control with 3-hr torsion and detorsion, Group 3: 50 mg/kg p.o. metformin 30 min before 3-hr torsion, Group 4; metformin just after detorsion, Group 5; metformin 30 min before torsion and just after detorsion. Bilateral ovaries and blood sample were obtained seven days after detorsion for biochemical and histopathological evaluation. ResultsOvarian tissue total anti-oxidant status (TAS) levels were significantly increased in group 4 when compared to group 1, 2 and 3 (all p < 0.01). In addition, there was a significant decrease in tissue oxidative stress index (OSI) level in group 4 with respect to group 2 (p < 0.01). Moreover, serum levels of OSI were significantly higher in group 2 with respect to group 1 and 5 (both p < 0.05). Similarly, there was significant increase in serum levels of peroxynitrite in group 2 as compared to serum levels in group 3 and 5 (p < 0.01 and 0.05, respectively). Furthermore, there were significant decrease in histopathological scores metformin and sham groups when compared to rats in the control group (Group 2). ConclusionMetformin reduces ischemia reperfusion injury in rat torsion detorsion model by improving histopathological and biochemical findings including TAS, OSI and peroxynitrite.

The relationship between thyroid function tests and sleep quality: cross-sectional study.

IntroductionThe relationship between sleep and hormones have long been recognized. Studies indicated that sleep quality is one of the major modulatory effects on the endocrine system. In this study, we aimed to assess the serum concentration of thyroid hormones in individuals who suffered from low quality sleep.Material and MethodsBased on the Pittsburgh Sleep Quality Index and ISMA Stress questionnaire, we divided 83 participants into two groups. Forty-one individuals with low quality sleep group and 42 with good quality sleep group, all from the male students of a medical school in Tehran, Iran, participated in this descriptive and cross-sectional study. Then, serum levels of thyroid hormones including free T3, free T4, and TSH were assessed and compared between two groups.ResultsThere were a significant increase in serum levels of FT4 (p=0.01) and TSH (p=0.02). There were also meaningful correlations between sleep score and stress score (p=0.008) as well as stress score and FT4 (p=0.03) in the case group.ConclusionsThe current study showed that thyroid function tests (T4 and TSH) significantly rose in the poor sleep condition. We also found correlations between sleep score, stress score, and FT4 in the poor sleep condition group that suggest low sleep quality can affect thyroid hormones.

Susceptibility of young and adult rat kidneys to impacts of mosquito coil fumes

ABSTRACT The present study aimed to investigate the effect of exposure to mosquito coil fumes (6 hr/day, 6 days/week, for 4 weeks) on the biochemical and histological structure of kidney in young and adult male rats. Atomic analysis of the coil was estimated to indicate the main constituent elements of the coil. Results showed a non-significant change in body weight gain and somatic indices, except for the heart somatic index that increased significantly in both ages compared to control groups. Biochemical analysis showed a significant increase in serum levels of creatinine, urea, uric acid, neutrophil gelatinase-associated lipocalin (NGAL), cystatin C. However, serum total protein content was reduced significantly. Urine analysis showed a marked increase in creatinine, urea, total protein, microalbuminuria, and NGAL, along with a significant reduction at glomerular filtration rate (GFR). Moreover, serum and urine Na+ and K+ levels showed no obvious changes in both ages compared to control groups, except for serum sodium in the young group. Histopathological examination confirmed the destructive effect of coil fumes on tubules and glomeruli of exposed kidneys, which was obvious in young than adult rats. Thus, inhalation of coil fumes may provide a serious risk on the kidney health of exposed human beings

Doxycycline Toxicity in Rats: Clinicobiochemical and Histopathological Studies

Doxycycline (DOX) is one of widely used antibiotics for treatment of different diseases in human and animals. This study aimed to evaluate the toxic effects of DOX on different organs in rats. The experiment was carried out on forty albino rats, they were randomly divided into four equal groups (10/each): Group 1 served as control group, Group 2 received doxycycline hyclate 5 mg/Kg Bwt, Group 3 received doxycycline hyclate 25 mg/Kg Bwt and Group 4 received doxycycline hyclate 50 mg/Kg Bwt. DOX was given intragastrically twice daily (12 hours interval) for 4 weeks. The results revealed a significant increase in serum level of liver enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT)), increased serum total protein, albumin and globulins, elevated serum levels of urea and creatinine, in addition to an increase in cardiac toxicity indicators (lactate dehydrogenase (LDH), and creatine kinase (CK)-MB enzymes and troponin-I). Also, there were significant increase in levels of malondialdehyde (MDA) and significant depletion of reduced glutathione (GSH) content besides various histopathological alterations in liver, kidneys and heart of DOX treated groups.

Susceptibility role of soluble HLA-G and HLA-G 14-bp insertion/deletion polymorphism in inflammatory bowel disease

BackgroundInflammatory bowel disease (IBD) is a group of chronic inflammatory disorders of the gastrointestinal tract. It is fundamentally related to a dysregulated immune response in the intestinal mucosa against microbiota in genetically predisposed individuals. Among the genetic and immunological factors that are suggested to have role in etiology and pathogenesis of IBD are human leukocyte antigen (HLA)-G molecules. Therefore, soluble HLA-G (sHLA-G) serum level and genetic association with HLA-G 14-bp insertion (Ins)/deletion (Del) polymorphism was analyzed in 100 IBD patients; 50 ulcerative colitis (UC) and 50 Crohn’s disease (CD), and 100 controls.ResultssHLA-G level was significantly elevated in IBD patients compared to controls (174.7 ± 27.1 vs. 126.8 ± 15.1; corrected probability [pc] < 0.001). The level was also elevated in UC patients compared to CD patients but the difference was not significant (180.5 ± 27.1 vs. 168.9 ± 26.3; p = 0.059). Receiver operating characteristic analysis confirmed the significance of sHLA-G in total IBD, UC, and CD patients (area under curve = 0.944, 0.961, and 0.927, respectively). The genetic association was analyzed under five genetic models (allele, recessive, dominant, overdominant, and codominant). At the allele level, Del allele frequency was significantly increased in total IBD patients (Odds ratio [OR] = 1.93; 95% confidence interval [CI] = 1.27–2.94; pc = 0.018) and CD patients (OR = 2.08; 95% CI = 1.23–3.54; pc = 0.042) compared to controls. Among UC patients, a similar increased frequency was observed, but the pc value was not significance (OR = 1.79; 95% CI = 1.07–3.00; p = 0.031). At the genotypic level, Del/Del genotype was associated with a significantly increased IBD-risk in total patients under codominant model (OR = 4.06; 95% CI = 1.56–10.56; pc = 0.024). sHLA-G level was not influenced by the Ins/Del polymorphism.ConclusionsThis study demonstrated a significant increase in serum level of sHLA-G in UC and CD patients. Further, HLA-G 14-bp Ins/Del polymorphism may be associated with susceptibility to IBD, particularly CD.

A scientific compendium of the effects of sildenafil citrate on the liver, kidney and heart of male albino rats at Nnewi, South East Nigeria

This study investigated the various effects of Sildenafil citrate on the liver, kidney and heart of male albino rats. Twenty eight male rats randomly divided into 4 groups and weighing 131-214g were used. While the animals in group 1 (control) received food and water only, those in the study groups 2,3&amp;4 respectively received 25mg/kg, 50mg/kg and 100mg/kg of Sildenafil citrate orally, daily for 4 weeks. All animals were sacrificed and blood samples collected by cardiac puncture for analysis of biochemical parameters. The rats Liver, kidneys and hearts were subjected to histopathological tests. Study results showed no changes in food consumption, fluid intake, body weight and relative organ weight of the animals. The animals in group 4 showed significant increase in mean Lactate dehydrogenase and Aspartate aminotransferase ⃰(P&lt;0.05) compared to control. Mean levels of creatinine was significantly higher among group 4 animals ⃰(p&lt;0.05) but not significantly high among the animals in other groups. Mean Na+ and Cl- level were significantly high among the animals in group 4 ⃰(p&lt;0.05). Although no histopathological changes were observed in the heart of the rats in groups 2,3 and 4, there were significant increase in serum levels of Na+, K and Cl- of animals in group 4 which could have affected their heart owing to fatigue. Sildenafil citrate (100mg/kg) caused distortion in cyto-architecture of the liver and mild distortion of cortical structures in the kidneys of albino rats. Sildenafil citrate has potential toxic effects on the liver, kidney and heart of studied rats with higher doses. Conclusion: Sildenafil citrate has potential toxic effects on the liver, kidney and heart of male albino rats especially with higher doses.

Sub-acute toxicity of Caladium bicolor (Aiton) leaf extract in Wistar rats

Herbal medicinal plants constitute an integral component of plant biodiversity whose application for therapeutic purposes has been a common practice since antiquity. However, studies have reported tissue pathologies following exposure to herbal medicinal plants or extracts. This study was carried out to assess the possible pathological effects of sub-acute exposure of methanol extract of Caladium bicolor on the hepatic histomorphology of experimental Wistar rats. Twenty four Wistar rats were divided into four groups A-D. Group A was administered with distilled water (2 ml/kg b.w) and groups B-D administered with 100 ml/kg, 200ml/kg and 300ml/kg b.w. of the extract respectively for twenty eight days. The bodyweight of experimental animals was recorded at regular intervals during the study period. After the treatment period, hepatic tissue was harvested, weighed and processed for histopathological study. The results showed that exposure to the extract causes significant (p&lt;0.05) body and organ weight reduction, a significant increase in serum level of ALT and AST as well as prominent hepatic histopathological changes such as inflammation, necrosis and steatosis. Sub-acute exposure to methanol extract of C. bicolor thereby causes dose-independent hepatopathy in experimental animals. Hence, its application for therapeutic purposes needs to be re-evaluated and preferably discontinued to avoid these associated hepatic tissue pathologies.

Dynamics of Galectin-3 serum levels after percutaneous occlusion of the left atrial appendage: a new surrogate parameter for successful LAA closure?

Abstract Introduction Left atrial cardiac tissue remodeling following left atrial appendage closure (LAAC) is a scientifically neglected phenomenon until now but might have impact on functional outcome of patients suffering from atrial fibrillation (AF). Thus, our study is focused on quantification of key biomarkers reflecting fibrosis development as a major component within cardiovascular tissue remodeling. Methods Patients (CHA2DS2VASC score ≥1, HASBLED score ≥3) with bleeding complications under anticoagulation therapy and therefore eligible for LAAC were included in the present study. Serum levels of biomarkers of cardiac fibrosis and remodeling (Galectin-3, ST2/IL-2, ST2/IL-1, B domain containing Tenascin-C (B+ Tn-C), C domain containing Tenascin- C (C+ Tn-C)) were determined before device implantation (baseline), 45 days (45d) and 6 months (6M) after LAAC using commercially available ELISAs. To quantify functional outcome, all patients performed a 6-minutes walk test (6- MWT). Transesophageal echocardiography (TEE) was carried out to assess success of the LAAC procedure regarding peri-device leakage (PDL). Results We included 33 patients (age: 73.5±6.7 years; 21 men (64%) and 12 women (36%); BMI: 29.1±5.1 kg/m2; CHA2DS2VASC score: 4.2±1.2; left ventricular ejection fraction: 61.1±9.3%; mean occluder size: 25.9±3.9 mm; type of AF: 46% paroxysmal (15 patients), 55% permanent (18 patients)). Complete LAAC (without any residual low) was achieved in 60% (19 patients) after 45 days and in 87% (29 patients) after 6 months. At baseline, Galectin-3 levels did not show a relevant difference regarding the type of AF (paroxysmal AF: 14.7±5.4 ng/ml vs. permanent AF: 13.1±6.3 ng/ml; p=0.45). We observed a significant increase of serum levels of Galectin-3 [ng/ml] after 45 days vs. baseline (baseline: 13.3±5.8 vs. 45d: 18.3±10.6; p=0.005) with a return to baseline levels after 6 months (baseline: 13.3±5.8 vs. 6M: 12.5±5.4; p=0.28). Compared to patients with successful LAAC, patients with PDL had a trend towards higher levels of Galectin-3 after 6 months (11.3±5.5 ng/ml vs. 16.1±4.1 ng/ml, p=0.09). Measurements of other fibrosis markers were statistically not significantly different. The walking distance measured by the 6-MWT increased significantly from 298.5±89.5 meters at baseline to 335.5±95.1 meters (p=0.04) after 45d and remained significantly elevated after 6M (346.7±122.7 meters; p=0.02). Conclusion The implantation of an LAA occluder device is accompanied by significantly increased circulating levels of the fibrosis biomarker Galectin-3 after 45 days in patients with AF. The regression in serum levels after 6 months probably reflects a successful fibrotic remodeling in the left atrial appendage over time and might be used as surrogate parameter for LAAC success. Increased and stable exercise tolerance after 45 days can be observed. Funding Acknowledgement Type of funding source: None

The effect of 12-week resistance exercise training on serum levels of cellular aging process parameters in elderly men.

Regular physical activity has a positive effect on the prevention of cellular aging. The present study investigated the effect of 12-week resistance training (RT) on serum levels of Sirtuin-1 (SIRT1), Sirtuin-3 (SIRT3), Sirtuin-6 (SIRT6), Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), and telomerase enzyme in elderly men. For this purpose, 30 elderly men (age 66.23±0.57years) were randomly divided into two groups: resistance training group (RET, n=15) and control group (CTR, n=15). Participants in RET performed RT protocols with intensity of 60% one-repetition maximum (3×/week, 4 sets of the six exercise circuits). Body composition, physical functioning and, blood samples were assessed before (pre-test) and after (post-test) a 12-week intervention. The results showed that there was a significant increase in serum levels of SIRT1 (P=0.001), SIRT3 (P=0.001), SIRT6 (P=0.02), PGC1-α (P=0.001), and telomerase enzyme (P=0.001) in RET. Also, we found a significant difference between the RET and CTR in serum levels of SIRT1 (P=0.001), SIRT3 (P=0.001), SIRT6 (P=0.037), PGC1-α (P=0.007), and telomerase enzyme (P=0.001). 12-Week RT increased the levels of proteins associated with the biological aging process in elderly men. It seems that the RT may have beneficial effects on cellular senescence and also improved impaired mitochondrial protein and enzymatic functional induced aging.