Significant Increase In Serum Levels Research Articles

Comparative study between the effect of mesenchymal stem cells and/or platelet-rich plasma on bone parameters in ovariectomized mature rats

Abstract Background Osteoporosis is a common bone disease and is associated with considerable morbidity and mortality. Osteoporosis occurs most frequently in postmenopausal women. The inadequacy of current treatments and their side effects have driven a search for improved methods of dealing with osteoporosis. Design Experimental study. Aim of Work This study was conducted to throw light on the ability of BM-MSCs and/or PRP in improving bone formation and slow down bone loss in ovariectomized rats with osteoporosis. Materials & Methods This study was carried out on adult female Wistar rats allocated randomly into five groups: Sham-operated, OVX untreated, OVX-MSCs treated (MSCs administered once intravenously), OVX/PRP treated (PRP administered once subcutaneously), OVX-MSCs/PRP treated groups. Rats were subjected to assessment of serum ALK, CTX-1, MDA and TNF-α. In addition, specimens of tibia were taken and processed for light microscopic studies and morphometric analysis. Results OVX untreated group showed significant increases in serum levels of ALK and CTX-1. Significant elevations of serum MDA and TNF-α levels were also noticed in the OVX untreated group. Administration of BM-MSCs and PRP significantly lowered serum levels of ALK, CTX-1, MDA and TNF-α. These results were confirmed by the histopathological findings. Conclusion BM-MSCs together with PRP can partially reverse OVX-induced bone loss and halt osteoporosis progression. Abbreviations BM-MSCs: bone marrow derived mesenchymal stem cells, PRP: platelet-rich plasma, OVX: ovariectomized, ALK: alkaline phosphatase, CTX-1: cross linked c telopeptide of type 1 collagen, MDA: malondialdehyde, TNF-α: tumour necrosis factor-alpha.

The inhibitory mechanisms of losartan and vitamin D on amiodarone‐induced lung inflammation in rats: Role of mitogen‐activated protein kinases/activator protein‐1

Amiodarone (AMD), an antiarrhythmic drug, is used cautiously due to its lung toxicity that is characterized by alveolar inflammation followed by fatal fibrosis. AMD induces lung inflammation via increasing the alveolar macrophages and disturbing the balance of T-helper-1 (Th1) and Th2 cells cytokines. In this study, the role of the mitogen-activated protein kinases (MAPKs)/activator protein-1 (AP-1) pathway in AMD-induced lung inflammation was evaluated. Also, the anti-inflammatory and antifibrotic effects of losartan and/or vitamin D were investigated following 7, 14, and 28 days of AMD administration. AMD resulted in lung injury, inflammatory infiltration, and increased pulmonary levels of inflammatory cytokines starting from Week 1 of exposure. A significant increase in serum levels of interleukin-4 along with a significant reduction of interferon-gamma, in addition to strong expression of CD68, were reported after 14 and 28 days of AMD administration reflecting Th1/Th2 cytokines imbalance and the accumulation of alveolar macrophages, respectively. The phosphorylation of MAPKs (ERK1/2, JNK, p38) and AP-1 was significantly enhanced starting from Week 1 of exposure. Marked expression of transforming growth factor beta-1 and massive deposition of collagen were detected after 28 days reflecting late fibrosis. All these abnormalities were significantly mitigated by vitamin D and its combination with losartan. Losartan alone has less prominent anti-inflammatory effects particularly after 28 days; however, it efficiently prevented late fibrosis. This study concludes that MAPKs/AP-1 pathway is involved in AMD-induced lung inflammation and that vitamin D and/or losartan could be used as a prophylactic agent to prevent AMD-induced lung toxicity.

Fustin Ameliorates Elevated Levels of Leptin, Adiponectin, Serum TNF-α, and Intracellular Oxidative Free Radicals in High-Fat Diet and Streptozotocin-Induced Diabetic Rats.

Fustin is a prominent ingredient of Rhus verniciflua Stokes (Anacardiaceae) and has a wide range of pharmacological and clinical effects. The present study attempted to evaluate the antidiabetic potential of fustin in streptozotocin- and high-fat diet-induced diabetes in rats. The efficacy of fustin 50 mg/kg and 100 mg/kg/day p.o. was studied in 60% of total calories from fat as a high-fat diet along with single-dose administration streptozotocin (50 mg/kg, i.p.) experimentally induced diabetes in rats for 42 days. The mean body weight; blood glucose; and biochemical parameters such as lipid profile, total protein (TP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), insulin, leptin levels, adiponectin levels, glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activity in serum were measured. The rats’ weight was maintained in the fustin groups compared to the diabetic control group. Diabetes caused a significant increase in serum levels in blood glucose, lipid profile, MDA, TNF-α, ALT, and AST parameters and a decrease in serum insulin, adiponectin, leptin, GSH, SOD, and CAT compared to healthy rats. The treatment regimen with fustin (50 and 100 mg/kg) significantly restored all serum parameters in test groups. The present study found clinical evidence for the first time regarding the significant antidiabetic property of fustin, which could be a worthwhile candidate for the treatment of diabetes.

Informativeness of laboratory methods of research of pregnant women with chronic inflammatory bowel disease

Annotation. The aim of the work is to demonstrate the importance of laboratory parameters in pregnant with chronic inflammatory bowel disease. The examined patients were divided into the main group (ulcerative colitis, n=40) and the control group (practically healthy women, n=30). The formation of observation groups was carried out by methods of continuous and selective analysis. The indicators of vasculo-endothelial growth factor (VEGF), serum levels of vitamin D, homocysteine, markers of neutrophilic intestinal inflammation (serum levels of tumor necrosis factor α and interleukin-4 were studied). Database formation and all calculations were performed using the software packages STATISTICA6.1 (№АХХR910F374605FA) and MedCalc (version 17.7.7, MedCalcSoftware). Statistical processing of quantitative data included the calculation of the mean and standard error of the mean (± m) using parametric criteria (in the case of a normal distribution law) or a nonparametric Mann-Whitney test (if the distribution law differs from the normal one). In the analysis of the informativeness of laboratory methods, it was found that women with chronic inflammatory bowel disease were characterized by: increased levels of fecal calprotectin, proinflammatory cytokines TNFα and interleukin-4, homocysteine. The analysis of markers of endothelial dysfunction in pregnant women with COPD was diagnosed with a significant increase in serum levels of vasculo-endothelial growth factor and an increase in microalbuminuria, which allowed to talk about the association of ulcerative colitis with the development of gestational endotheliopathy in such women.

Reduction of Effects of Dietary Aflatoxin B1 on Biochemical Parameters of the Fish Clarias Batrachus by Vitamin C

Aflatoxins are produced mainly by molds Aspergillus flavus and Aspergillus parasiticus. They cause toxicity called aflatoxicosis in animals and human beings which is of great concern in aquaculture also. Aflatoxin B1 is the most potent of all the known aflatoxins which mediates its effects by producing reactive oxygen species (ROS) and by irreversible damage to DNA and proteins leading to genotoxicity and cytotoxicity. Vitamin C is a potent antioxidant and reduces reactivity of ROS by donating electrons to them. Previous investigations suggest its role in alleviating aflatoxicosis in Nile tilapia. Present studies were conducted to determine the reduction in the negative effects of aflatoxin B1 on blood biochemical parameters and liver glycogen of fish Clarias batrachus by dietary supplementation of vitamin C. In the present investigation 60 fish were divided into four groups. Each group comprised fifteen fish. Four types of feed were prepared on the basis of presence of aflatoxin B1 and vitamin C. Feed I consists of a basal diet given to the first group of fish or control. Feed II consisted of aflatoxin B1 contaminated feed given to second group of fish. In feed III and IV 300 mg/kg and 600 mg/kg vitamin C was added to aflatoxin B1 contaminated feed The objective of the present investigation was to explore the role of Vitamin C in reduction of adverse effects of aflatoxin on plasma biochemical parameters and liver glycogen of the fish Clarias batrachus. The group of fish that was given the feed II showed a significant increase in serum level of ALT, AST, bilirubin, blood urea, glucose and albumin globulin ratio but significant decrease was observed in total serum proteins and liver glycogen as a result of dietary aflatoxin .Supplementation of Vitamin C in the feed significantly decreased the adverse effects of aflatoxin and the parameters showed significant improvement. The group of fish fed with 600 mg/kg vitamin C showed best results and were nearly similar to those of the control. The present investigation revealed that feed containing 600 mg/kg vitamin C diminishes the effect of aflatoxin B1 in the fish reducing the health risk in humans consuming the fish as aflatoxins has the potential to accumulate and stay in the tissues of animals for long period of time.

REPRODUCTIVE HORMONE LEVELS AND METABOLIC SYNDROME IN WOMEN WITH POLYCYSTIC OVARY SYNDROME IN SANA'A, YEMEN

Background and Objectives: Polycystic ovary syndromes (PCOs) are the most complex endocrine disorders of the female reproductive system with metabolic and psychiatric manifestations. It affects 5%-10% of women of childbearing age. There are paucity of information on PCOs. Therefore the present study aimed at the effect of reproductive hormones, metabolic syndromes, smoking and khat chewing on the PCOs among women in Sana'a Subjects and Methods: The study included 45 Yemeni women of the age group 18-45 years with PCOS classified into two groups regarding age: Group I 18-29 years old, Group II 30-45 years old and underwent clinical assessment (waist, BMI and sex hormones, blood pressure, glucose, lipids, and insulin), and transvaginal ultrasound. Clinical data, history of other diseases and data of chewing and smoking also collected.” Also the study included 45 healthy control women matched in age with the cases. Results: The prevalence of MS among PCOs patients was 35% and the most prevalent MS risk factors among PCOs patients were waist circumference (WC) 64.4%, and HDL-C 64.4% respectively, while prevalence of triglycerides (TG), hypertension and fasting blood sugar (FBS) were 28.9%, 20% and 13.3%, respectively. PCOs patients had significant increase in serum levels of luteinizing hormone (LH) (p<0.001), Insulin (p<0.001), HOMA-IR (p<0.001), T testosterone (TT) (p<0.001), DHEA-S (p<0.001) and FBS (p<0.016). Lean PCOs patients had a significant increase in TT than overweight/obese PCOs (p < 0.045) and dehydroepiandrosterone sulfate (DHEA-S) was found to be significantly higher in PCOs women with MS (p<0.011). Insulin resistance was significantly higher in PCOs women with hypertension as compared to PCOs women without hypertension (p<0.023). Conclusion: There is a relationship between PCOS and reproductive hormone disorder. Patients had significant increases in serum levels of LH, LH/Follicle Stimulating Hormone (FSH), Insulin, TT, and DHEA-S. Also, a relationship was found between the syndrome and infertility, hirsutism, irregular menstruation, polycystic ovaries and multiple sclerosis. Peer Review History: Received: 10 July 2021; Revised: 12 August; Accepted: 6 September, Available online: 15 September 2021 Academic Editor: Prof. Cyprian Ogbonna ONYEJI, Obafemi Awolowo University, Ile-Ife, Nigeria, conyeji@oauife.edu.ng UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewers: Prof. Dr. Hassan A.H. Al-Shamahy, Sana'a University, Yemen, shmahe@yemen.net.ye Dr. DANIYAN Oluwatoyin Michael, Obafemi Awolowo University, ILE-IFE, Nigeria, toyinpharm@gmail.com Similar Articles: A RETROSPECTIVE STUDY OF THE TREATMENT RESULTS OF 40 DIVERSE PATIENTS OF ANEMIA

The Role of Butyric Acid in Treatment Response in Drug-Naïve First Episode Schizophrenia.

Background: Butyric acid, a major short-chain fatty acid (SCFA), has an important role in the microbiota–gut–brain axis and brain function. This study investigated the role of butyric acid in treatment response in drug-naïve first episode schizophrenia.Methods: The study recruited 56 Chinese Han schizophrenia inpatients with normal body weight and 35 healthy controls. Serum levels of butyric acid were measured using Gas Chromatography-Mass Spectrometer (GC-MS) analysis at baseline (for all participants) and 24 weeks after risperidone treatment (for patients). Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) for patients at both time points.Results: At baseline, there was no significant difference in serum levels of butyric acid between patients and healthy controls (p = 0.206). However, there was a significant increase in serum levels of butyric acid in schizophrenia patients after 24-week risperidone treatment (p = 0.030). The PANSS total and subscale scores were decreased significantly after 24-week risperidone treatment (p's < 0.001). There were positive associations between baseline serum levels of butyric acid and the reduction ratio of the PANSS total and subscale scores after controlling for age, sex, education, and duration of illness (p's < 0.05). Further, there was a positive association between the increase in serum levels of butyric acid and the reduction of the PANSS positive symptoms subscale scores (r = 0.38, p = 0.019) after controlling for potential confounding factors.Conclusions: Increased serum levels of butyric acid might be associated with a favorable treatment response in drug-naïve, first episode schizophrenia. The clinical implications of our findings were discussed.

P–714 Insulin-like growth factor-I as a mediator of the effect of transdermal testosterone in poor responder patients

Abstract Study question Is insulin-like growth factor-I (IGF-I) a mediator of the effect of transdermal testosterone (TT) in poor responder (PR) patients? Summary answer IGF-I might be a mediator of the effect of TT in PR patients who undergo an IVF cycle What is known already Many strategies have been tried to improve the results in PR patients. Androgen supplementation with TT is the only that has significantly increased live birth rate in these patients. The mechanism by which TT might influence on the better results remains unclear but it is likely mediated or facilitated by IGF-I. Testosterone increases the number of primordial follicles, increase IGF-I by threefold and increase IGF-I receptor mRNA by fivehold in primordial follicles in primates. Some studies have suggested that IGF-I could be a parameter that reflects the endocrinological environment of mature follicles, which is correlated with oocyte and embryonic quality Study design, size, duration This prospective cohort study of 93 women PR according Bologna criteria treated with TT and IVF/ICSI was conducted between May 2015 and December 2016 Participants/materials, setting, methods Exogenous andogenization with TT for 5 days prior to ovarian stimulation was carried out. Hormonal parameters were evaluated: basal FSH, LH and Estradiol, AMH, IGF–1 pre and post TT. Ultrasound parameterswere also analysed: antral follicle count (AFC) and number of pre-ovulatory follicles the day of HCGr. We compared these parameters according to the ovarian response: adequate (&amp;gt; 4 oocytes) or insufficient (&amp;lt;3 oocytes), as well as the pregnancy was achieved or not. Main results and the role of chance Baseline characteristics of the patients were: 36.9 years, FSH 11.8, AMH 0.86 and RFA 5.3. In 83% of the patients the oocyte retrieval was carried out, obtaining an average of 3.8 MII oocytes and 2.9 embryos of 2pn with a clinical pregnancy rate per transfer of 33.3%. The FORT Test (AFC/pre-ovulatory follicles x100) was 70%, higher than that observed in other studies with patients with PR without TT (55%). In cases in which an insufficient response was obtained (&amp;lt;3 oocytes) or the cycle was canceled, a higher age and FSH and lower AMH were observed (p &amp;lt; 0.05). There were no differences in the rest of the parameters. Evaluating the hormonal and ultrasound parameters depending on whether or not pregnancy was achieved, a significant increase in IGF1 pre and post-TT was observed in the cases of pregnancy (31.5%) compared to those cases where there was no pregnancy (10.9%) (p = 0’01). There were no differences in the rest of the parameters. A significant correlation was found between AMH, AFC and increase in IGF-I levels (p &amp;lt; 0’05). Limitations, reasons for caution This a prospective cohort study with limited number of patients included. Wider implications of the findings: The significant increase in serum levels of IGF–1 in pregnant patients would indicate the existence of a more favorable clinical setting for the administration of testosterone, probably related to a more favorable ovarian reserve as demonstrated by its correlation with serum levels of AMH and with the AF. Trial registration number Not applicable

Evaluation of Serum Cyclooxygenase, Hepcidin Levels in Acute Renal Injury (AKI) Patients Following Cardiac Catheterization.

Acute kidney damage is a severe condition common in patients who have undergone heart surgery (catheterization) and secondary injury is also referred to as being synonymous with surgery. The goal of this research is to determine the rate of cyclooxygenase and hepcidin levels in patients with acute renal injury (AKI) following cardiac catheterization. The study is performed on (81) patients (64 males and 17 females) aged 40-75 years. Data from most patients are reported in the form of age, gender, and smoking background questionnaire. The results indicate a significant increase in serum levels of cyclooxygenase and hepcidin levels in patients with severe renal insufficiency after cardiac catheterization by (79%) males versus (21%) females. In this study, improved risk prediction could enhance patient monitoring and treatment after surgery, direct patient treatment and decision making, and enhance participation in AKI interventional trials.

Abstract 517: Tebentafusp induces transient systemic inflammation and modifies the micro-environment to sensitize uveal melanoma tumors to cytotoxic CD8 cells

Abstract Background: Tebentafusp is a unique investigational TCR-anti-CD3 bispecific fusion protein that targets melanoma-expressed gp100 antigen and has shown monotherapy activity in advanced metastatic melanoma [1, 2, 3]. In a phase I/II trial (NCT02570308) that enrolled late stage metastatic uveal melanoma patients, we explored the effects of tebentafusp on serum cytokines and on the tumor and its micro-environment. Methods: NCT02570308 was conducted in HLA-A*02:01+ patients with advanced uveal melanoma: This analysis focuses on patients who went through weekly dosing at Cycle 1, Day1 (C1D1, 20mcg) and C1D8 (30mcg), followed by a dose of 68mcg administered weekly at C1D15 onwards. Serum samples and tumor biopsies were taken pre-treatment and at multiple time points post-treatment, and were profiled as follows: a multiplex panel of 11 immune markers (Luminex) in sera from 124 patients; immunohistochemistry (IHC) and genome-wide transcriptional RNAseq analysis of up to 57 paired baseline and on-treatment biopsies at C1D16. Whole slide digital image analysis was used to calculate positive IHC cells per mm2 in the tumor. Results: Tebentafusp caused transient immune activation as evidenced by significant increases in serum levels of IFNγ and IFNγ-inducible chemokines including CXCL9/10/11 reaching maximal changes at 8-24 hours after dosing (fold change FC: 8-10). Induction of the T cell cytokines IL-2 and IL-10 was accompanied by transient increases in the inflammatory cytokines IL-6, TNFα and the chemokine CCL2 (FC: 5-14).After 3 doses of tebentafusp, a significant increase in CD3 positive immune cells in the tumor was seen (p&amp;lt;0.001; FC=3), particularly cytotoxic CD8+ cells, (p=0.002; FC=2). RNAseq analysis revealed significant induction of IFNα (FC=2) and IFNγ (FC=2) signatures. mRNAs known to be induced by IFNγ and implicated in response to anti-PD1/L1 were significantly increased: CXCL9/10/11, GZMB (FC=3-5). Expression of antigen presentation genes including HLA class 1, TAP1, 2 and PSMB8 was significantly induced (FC=2-3). Homeostasis mechanisms characterized by IDO1 and PD-L1 were induced (FC=4 and 2 respectively); however, low baseline FOXP3 expression levels were unchanged. These immune responses were accompanied by significant reductions in expression levels of tumor-specific melanoma markers gp100 and TYRP1 (30-40% reduction) and tumor proliferation genes including MKI67, BIRC5, CDK2 (20-30% reduction). Conclusions: Tebentafusp caused transient increases in inflammatory cytokines and chemokines in serum and modified the micro-environment of metastatic uveal melanoma tumors to sensitize to cytotoxic CD8+ cells.[1] NCT01211262; ASCO 2019 [2] Clinical Cancer Research; 2020.[3] #195; ESMO IO; 2020 Citation Format: Marcus O. Butler, Sarah Stanhope, Revashnee Naidoo, Emma Leach, Sarnjeet Kaur, Laura Collins, Shaad Abdullah, Koustubh Ranade, Alexander N. Shoushtari. Tebentafusp induces transient systemic inflammation and modifies the micro-environment to sensitize uveal melanoma tumors to cytotoxic CD8 cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 517.

Effectiveness of Echinacea purpurea extract on immune deficiency induced by azathioprine in male albino rats

This study was performed to evaluate the effectiveness of Echinacea purpurea (E.P.) on azathioprine (AZA)-induced immune deficiency in albino rats. Thirty six male albino rats were divided into six equal groups. The first group served as normal control, the second and third groups were treated with two doses of AZA (3 and 5mg/kg/b.w/day IP), respectively for six weeks. The fourth group was treated with 50 mg kg/b.wt/day of Echinacea. The fifth and sixth groups were treated with3 and 5 mg AZAm respectively followed by50 mg E.P. administration. At the end of the experimental period, both doses of AZA revealed a significant reduction in total body and spleen weights, increase in tissue total protein with a significant increase in serum total protein and albumin, a marked decrease in the number of WBCS associated with a decrease in the number of lymphocytes, a significant decrease in serum total anti-oxidant capacity. Also,concentration of immunoglobulins (IgG and IgM) and interleukins (IL4 &amp;IL6) showed a significant increase, while the level of IL10 decreased significantly in splenic tissue. The dose of AZA (5 mg /kg b.wt.) only resulted in a highly significant increase in serum level of T3 and T4. However, treatment with Echinacea purpurea extract had a significant influence on immune deficiency induced by azathioprine. These findings demonstrated that E.P. extract is a promising immunomodulatory agent with a potent therapeutic value in stimulating the immune response.

Serum Uric Acid Level and Inflammation in Obese Medical Students at Ain Shams University

Abstract Background: Overweight and obesity occur when excess fat accumulation increases risk to health, leading to expression of co-morbid diseases occur at different thresholds. That's why obesity is now recognized as a chronic or non-communicable disease. Aim of Study: To assess serum uric acid and diet contrib-uting in its increased concentration level in relation to inflam-mation in a subsample of obese medical students as compared to normal-weight medical students in Faculty of Medicine Ain Shams University. Subjects and Methods: The current study is a case control study of 63 students among 1220 Ain Shams medical students. Our study group was divided into two groups. Group 1 included 30 students with BMI between 18.5-24.9Kg/m2. Group 2 included 33 students with BMI >!30Kg/m2. Results: There was significant difference between the two groups in weight, waist circumference and waist hip ratio, but not for height. As regards CRP serum level, the obese group showed significant increase in serum level. In the same time there was a significant positive correlation between the CRP serum level and BMI, WC and WHR in both groups. On the other hand, protein intake was significantly higher in obese group than normal weight group, as a part of increased caloric intake. When comparing serum uric acid level in the two groups there was a statistically significant difference, and on searching for a relation between the serum uric acid and BMI, WC, CRP and protein intake serum level, a positive correlation was found. Conclusion: Serum UA level is a crucial biomarker, it could induce inflammation and hence increases adiposity or its increase results from increased obesity. Moreover, increased serum uric acid is correlated to increased protein intake in obese individuals with increased total caloric intake specially protein content.

Hepatic ischemia reperfusion injury: effect of moderate intensity exercise and oxytocin compared to l-arginine in a rat model

BackgroundHepatic ischemia reperfusion (IR) injury is considered as a main cause of liver damage and dysfunction. The l-arginine/nitric oxide pathway seems to be relevant during this process of IR. Although acute intense exercise challenges the liver with increased reactive oxygen species (ROS), regular training improves hepatic antioxidant status. Also, oxytocin (Oxy), besides its classical functions, it exhibits a potent antistress, anti-inflammatory, and antioxidant effects. This study was designed to evaluate the hepatic functional and structural changes induced by hepatic IR injury in rats and to probe the effect and potential mechanism of moderate intensity exercise training and/or Oxy, in comparison to a nitric oxide donor, l-arginine, against liver IR-induced damage.ResultsCompared to the sham-operated control group, the hepatic IR group displayed a significant increase in serum levels of ALT and AST, plasma levels of MDA and TNF-α, and significant decrease in plasma TAC and nitrite levels together with the worsening of liver histological picture. L-Arg, Oxy, moderate intensity exercise, and the combination of both Oxy and moderate intensity exercises ameliorated these deleterious effects that were evident by the significant decrease in serum levels of ALT and AST, significant elevation in TAC and nitrite, and significant decline in lipid peroxidation (MDA) and TNF-α, besides regression of histopathological score regarding hepatocyte necrosis, vacuolization, and nuclear pyknosis. Both the moderate intensity exercise-trained group and Oxy-treated group showed a significant decline in TNF-α and nitrite levels as compared to l-Arg-treated group. The Oxy-treated group showed statistical insignificant changes in serum levels of ALT, AST, and plasma levels of nitrite, MDA, TAC, and TNF-α as compared to moderate intensity exercise-trained group.ConclusionThe combination of both moderate intensity exercise and Oxy displayed more pronounced hepatoprotection on comparison with l-Arg which could be attributed to their more prominent antioxidant and anti-inflammatory effects but not due to their NO-enhancing effect.

Adiponectin Gene Variant rs3774261, Effects on Lipid Profile and Adiponectin Levels after a High Polyunsaturated Fat Hypocaloric Diet with Mediterranean Pattern.

The role of ADIPOQ gene variants on metabolic improvements after weight change secondary to different hypocaloric diets remained unclear. We evaluate the effect of rs3774261 of ADIPOQ gene polymorphism on biochemical improvements and weight change after high polyunsaturated fat hypocaloric diet with a Mediterranean dietary pattern for 12 weeks. A population of 361 obese subjects was enrolled in an intervention trial with a calorie restriction of 500 calories over the usual intake and 45.7% of carbohydrates, 34.4% of fats, and 19.9% of proteins. The percentages of different fats was; 21.8% of monounsaturated fats, 55.5% of saturated fats, and 22.7% of polyunsaturated fats. Before and after intervention, an anthropometric study, an evaluation of nutritional intake and a biochemical evaluation were realized. All patients lost weight regardless of genotype and diet used. After 12 weeks with a similar improvement in weight loss (AA vs. AG vs. GG); total cholesterol (delta: −28.1 ± 2.1 mg/dL vs. −14.2 ± 4.1 mg/dL vs. −11.0 ± 3.9 mg/dL; p = 0.02), LDL cholesterol (delta: −17.1 ± 2.1 mg/dL vs. −6.1 ± 1.9 mg/dL vs. −6.0 ± 2.3 mg/dL; p = 0.01), triglyceride levels (delta: −35.0 ± 3.6 mg/dL vs. 10.1 ± 3.2 mg/dL vs. −9.7 ± 3.1 mg/dL; p = 0.02), C reactive protein (CRP) (delta: −2.3 ± 0.1 mg/dL vs. −0.2 ± 0.1 mg/dL vs. −0.2 ± 0.1 mg/dL; p = 0.02), serum adiponectin (delta: 11.6 ± 2.9 ng/dL vs. 2.1 ± 1.3 ng/dL vs. 3.3 ± 1.1 ng/dL; p = 0.02) and adiponectin/leptin ratio (delta: 1.5 ± 0.1 ng/dL vs. 0.3 ± 0.2 ng/dL vs. 0.4 ± 0.3 ng/dL; p = 0.03), improved only in AA group. AA genotype of ADIPOQ variant (rs3774261) is related with a significant increase in serum levels of adiponectin and ratio adiponectin/leptin and decrease on lipid profile and C-reactive protein (CRP).

Ischemia-modified albumin as a novel marker for diagnosis of necrotizing enterocolitis in newborn infants

Background: Necrotizing enterocolitis (NEC) is the most common neonatal gastrointestinal emergency. Ischemia-modified albumin (IMA) is a marker of oxidative stress and ischemia. Its role in early diagnosis of NEC has been little investigated so far. Aim: The objective of our research was to study the role of serum IMA in diagnosis of NEC in newborn infants. Material and methods: The study was carried out on 80 neonates; 40 with NEC and 40 controls, subjected to serum IMA dosage with ELISA. Results: There was a highly statistically significant increase in IMA in both preterm (60.59 ± 34.97 U/ml) and full-term infants with NEC (60.50 ± 29.88 U/ml) compared to their controls (11.28 ± 3.09 U/ml; 5.34 ± 1.88 U/ml). The positive predictive value of IMA in preterm and full-term with NEC was 100% and 94.74%, while the negative predictive value was 80% and 90.48%, respectively. There was a statistically significant increase in serum level of IMA in stage II NEC compared to stage I NEC as well as in non-survivor cases. Significant positive correlation between serum IMA level and duration of recovery from NEC was detected. Conclusions: IMA is a sensitive marker for diagnosis of NEC in full-term and preterm infants and can predict severity of NEC and death.

Synergetic Action of Forskolin and Mevastatin Induce Normalization of Lipids Profile in Dyslipidemic Rats through Adenosine Monophosphate Kinase Upregulation.

In the present study, we examined the synergetic effect of forskolin and mevastatin administration on lipid profile and lipid metabolism in omental adipose tissue in dyslipidemic rats. The study was conducted on forty male albino rats. The rats were randomly classified into four main groups of ten animals in each group as follows: group A, served as control nontreated; group B, rats that received Triton WR 1339 (500 mg/kg); group C, rats that received Triton WR 1339 with forskolin (100% FSK extract 0.5 mg/kg/day) for four weeks; and group D, dyslipidemic rats received both mevastatin and forskolin. At the end of the experimental period, blood and omental adipose tissue samples were collected, preserved, and used for biochemical determination of lipid profile and mRNA expression profile of adenylate cyclase (AC), hormone-sensitive lipase, respectively (HSL), and adenosine monophosphate-activated protein kinase (AMPK). The results showed a significant decline in the serum concentration of total cholesterol, LDL-cholesterol, and triglycerides, although there was a significant increase in serum levels of HDL-cholesterol and glycerol in rats received forskolin alone or with mevastatin when compared with control and dyslipidemic groups. The mRNA expression levels of AC, HSL, and AMPK were significantly increased in omental adipose tissue of rats received forskolin when compared with other groups. In conclusion, forskolin acts synergistically with mevastatin to lower lipid profile and improve lipid metabolism in dyslipidemic rats through upregulation of AMPK expression.

Evaluation of Serum IL-6 and FABP Levels in Acute Kidney Injury (AKI) Patients Following Cardiac Catheterization

Acute kidney damage is a severe condition common in patients who have undergone heart surgery(catheterization) and secondary injury is also referred to as being synonymous with surgery. The goal ofthis research is to determine the rate ofinterleukin-6 (IL-6) and fatty acid-related protein (FABP) in patientswith acute renal injury (AKI) following cardiac catheterization. The study is performed on (81) patients (64males and 17 females) aged 40-75 years. Data from most patients are reported in the form of age, genderand smoking background questionnaire. The results indicate a significant increase in serum levels of IL-6and FABP in patients with severe renal insufficiency after cardiac catheterization by (79%) males versus(21%) females. In this study, improved risk prediction could enhance patient monitoring and treatment aftersurgery, direct patient treatment and decision making, and enhance participation in AKI interventional trials.

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

Background and aimsChronic 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 not well understood whether a combination therapy with 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. MethodsMale C57BL/6J mice received one intraperitoneal injection of saline or DOX-2 mg/kg and CPS-50 mg/kg once a week for 4 weeks. After the treatment period, liver histology and various serum biomarkers of hepatotoxicity were assessed. ResultsCo-treatment with 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. ConclusionsTaken 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.

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.