Hayam G. Sayyed

The effect of melatonin on plasma markers of inflammation and on expression of nuclear factor-kappa beta in acetic acid-induced colitis in the rat.

Background and AimsMelatonin may be involved in gastrointestinal tract physiology and could affect inflammation-related gastrointestinal disorders. Rat models of ulcerative colitis imply melatonin is beneficial. To determine potential pathophysiological mechanisms, we assessed colonic nuclear factor-kappa beta expression and measured serum levels of pentraxin-3, lipid peroxides, and total thiols in an acetic acid model of this disease.Materials and MethodsThirty rats were divided into five groups: a control group, an acetic acid-induced colitis group, a group treated with melatonin before colitis induction, a group treated short-term after colitis induction, and a group treated long-term after colitis induction. After four weeks, blood samples were taken for measurement of pentraxin-3, lipid peroxide, and total thiols. Sections of the colon were taken for histopathological examination and immunohistochemical detection of nuclear factor-kappa beta expression.ResultsMelatonin administration reduced nuclear factor-kappa beta immunohistochemical expression, reduced serum levels of lipid peroxide and pentraxin-3, and maintained serum levels of total thiols. However, in long-term treatment the protective effect of melatonin was not as marked.ConclusionMelatonin is effective in prevention and short-term treatment of the inflammatory process in acetic-acid induced colitis whereas the benefit of long-term treatment is unclear. Benefit may be linked to protection mechanisms against inflammatory processes by inhibiting the nuclear factor-kappa beta and conserving endogenous antioxidant reserves of total thiols, thus reducing the level of colonic damage possibly caused by lipid peroxides.

Implication of tumor necrosis factor alpha receptor 1 and hexosaminidase: relationship to pathogenesis of liver diseases

Liver disease is the main cause of morbidity and mortality worldwide. The spectrum of the disease ranged from fatty liver to hepatic inflammation, necrosis, progressive fibrosis, and hepatocellular carcinoma. We evaluated the serum levels of soluble tumor necrosis factor alpha receptor 1, total B-hexosaminidase and its isoenzymes Hex A and B activities, and nitric oxide in patients with liver diseases and their association with aminotransferase level. Seventy patients and 12 healthy subjects were recruited. Patients were divided into three groups: chronic hepatitis group (20 patients), liver cirrhosis group (30 patients), and malignant liver group (20 patients). Serum levels of soluble tumor necrosis factor alpha receptor 1, total B-hexosaminidase and its isoenzymes Hex A and B activities, and nitric oxide were measured. Serum levels of soluble tumor necrosis factor alpha receptor 1, total B-hexosaminidase activity, and nitric oxide were significantly higher in the liver disease patients. Serum levels of isoenzymes Hex A and B were significantly higher in malignant liver patients. Total B-hexosaminidase and its isoenzyme Hex A activity levels were significantly higher in positive HBsAg and positive anti-HCV patients. Serum levels of soluble tumor necrosis factor alpha receptor 1 were positively correlated with aminotransferase level. Taken together, these findings suggested that these biochemical indices might reflect ongoing disease activity and played an important role in the pathophysiology of liver diseases.

Treatment Efficiency of Different Routes of Bone Marrow-Derived Mesenchymal Stem Cell Injection in Rat Liver Fibrosis Model

Background/Aims: The most appropriate route for bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation in the management of liver fibrosis remains controversial. This study investigated the therapeutic efficacy of intravenous and intrasplenic BM-MSC transplantation on carbon tetrachloride (CCl4)-induced rat liver fibrosis. Methods: Fifty rats were divided into 5 groups (n = 10 rats per group): healthy control group, CCl4 group, CCl4/ recovery group, CCl4/BM-MSC intravenous group, and CCl4/BM-MSC intrasplenic group. BM-MSCs were isolated, labeled with green fluorescent protein (GFP), and injected into fibrotic rats either intravenously or intrasplenically. Gene expression of interleukins (IL-1β and IL-6), interferon (INF)-γ, hepatic growth factor, and the hepatocyte-specific marker cytokeratin 18 was estimated by quantitative real-time reverse transcription-polymerase chain reaction. Vascular endothelial growth factor and connective tissue growth factor was detected by western blot analysis and enzyme-linked immunosorbent assay, respectively. At 2 weeks after intravenous and intrasplenic BM-MSC injections, GFP-positive cells were detected in liver tissue. Results: Both routes achieved a similar enhancement of liver function, which was confirmed by histopathological examination. The intravenous route was more effective than the intrasplenic route in reducing gene expression levels of IL-1β, IL-6, and INF-γ. However, fibrotic changes were still observed in the recovery group. Conclusion: Intravenous BM-MSC injection was an efficient and appropriate route for BM-MSC transplantation for the management of liver fibrosis.

Superimposed effect of ovariectomy on type 2 diabetes mellitus in Wistar rats

Abstract Background Estrogen deprivation in the postmenopausal women plays a critical role in progression of type 2 diabetes mellitus (T2DM). Aim The present study investigated the overlaid effect of ovariectomy on T2DM and the possible underlying mechanism. Materials Forty female Wistar rats were divided into four groups (10 rats each): sham control, ovariectomized control, sham diabetic and diabetic ovariectomized groups. At the end of experiment, estimation of body weight gain percentage, food intake, fasting blood glucose concentration, and insulin tolerance test were done. Then, rats were euthanized and blood samples were taken for measurement of serum concentration of insulin, HOMA-IR, lipid parameters, tumor necrosis factor-α, interleukin 1 beta, interleukin 4, interleukin 10, malondialdehyde and total thiol. Also, histopathological and immunohistochemical examination of the pancreas were done. Results The present study revealed that ovariectomy aggravated the diabetic induced glucose metabolic disturbance as implied by impaired insulin tolerance test, increased insulin resistance alongside lipid dyshomeostasis. These metabolic disturbances might claim to exacerbation of oxidative stress and inflammatory response along with apparent histopathological and immunohistochemical changes on the pancreas. Conclusion We concluded that metabolic disturbances induced by diabetes might be getting worse after ovariectomy via intensification of oxidative stress and inflammatory state.

Effect of Vagus Nerve Stimulation on Focal Transient Cerebral Ischemia and Reperfusion in Adult Male White New Zealand Rabbits

Background: Oxidative stress has been implicated in the pathophysiology of cerebral ischemia. Pentraxin-3 plays an important role in innate immune responses and in inflammatory diseases. Our aim was to evaluate pentraxin-3 serum level on focal transient cerebral ischemia and reperfusion model in rabbits and to assess the anti-inflammatory and anti-oxidant effects of vagus nerve stimulation. Materials and methods: Focal transient cerebral ischemia and reperfusion was induced by occlusion of the right common carotid artery for 2 hours followed by reperfusion for one hour. Stimulating electrodes were implanted on the cervical part of the right vagus nerve. Vagus nerve stimulation was started 30 min following right common carotid artery ligation for a period of one hour. The stimulation signals were delivered every five minutes for 30 seconds. All the procedures were duplicated but no stimulus was delivered in the control group. Serum level of pentraxin-3, lipid peroxide and total thiols were determined at baseline, at end of ischemia and at end of reperfusion and the animal decapitated and neuronal damage was evaluated. Results: We found that vagus nerve stimulation caused reduction of the ischemic features with revival of the cell shape and size. It also resulted in decreased serum levels of pentraxin-3 and lipid peroxide whereas the level of total thiols was increased. Conclusion: We concluded that the observed diversity in pentraxin-3, lipid peroxide and total thiols serum levels in cerebral ischemia and reperfusion may reflect relative roles in the biology. Anti-inflammatory and anti-oxidant role of vagus nerve stimulation in cerebral ischemia and reperfusion may represent a marker of altered cerebral function, and may provide potential therapeutic applications.

Extracellular Matrix Turnover, Angiogenesis and Endothelial Function in Acute Lung Injury: Relation to Pulmonary Dysfunction and Outcome

Background : Acute lung injury (ALI) is a syndrome with a diagnostic criteria based on hypoxemia and a classical radiological appearance, with acute respiratory distress syndrome at the severe end of the disease. Occurrence of rupture of the basement membranes and interstitial matrix remodeling during ALI. Matrix metalloproteinases (MMPs) participate in tissue remodeling related with pathological conditions such as acute lung injury. We hypothesized the interrelationships between extracellular matrix (ECM) turnover as MMP-9 and indicator of angiogenesis such as angiopoietin-2 (Ang-2) as well as plasma von Willebrand factor (vWF) and their correlation with arterial partial pressure of oxygen (PaO2), oxygen saturation (SaO2) and mortality in ALI/ARDS. Methods : Eighty eight mechanically ventilated patients (68 male, mean (SD) age 61 (10) years) were compared to 40 healthy controls (36 male, mean (SD) age 57 (10)). All biomarkers were measured by Enzyme linked immunosorbent assay (ELISA). Oxygenation, body temperature, leucocytes, and platelet counts were noted. Results: Plasma levels of all biomarkers were significantly different, among ALI/ARDS subjects (p<0.001). They were inversely related to PaO2 and SaO2 and positively related to mortality. In addition, increased MMP-9, Ang-2 and vWF levels were interrelated on the first day of admission. Conclusions : The observed diversity in plasma levels of MMP-9, Ang-2 and vWF in ALI/ARDS patients revealed the activity and severity of the disease, shedding more light onto the pathogenesis and/or presentation of ARDS. Keywords: Acute lung injury, Matrix turnover, Pulmonary dysfunction