Role of Nitric Oxide and Endogenous Antioxidants in Thyroxine Facilitated Healing of Ischemia-Reperfusion Induced Gastric Ulcers

Background: Studies have revealed the role of thyroxine during healing of gastric ulcers with information lacking on the mechanism involved hence the focus of this study.Materials and Methods: Adult male Wistar rats (150 ­ 200g) were randomly divided into 4 groups (n=5 per group): Normal control (NC), Sham ulcerated (SU), Thyroidectomised ulcerated untreated (ThU) and Thyroidectomised ulcerated + Levo-thyroxine (100µg/kg/day) (ThU + T4). Animals were stabilised for 35 days following thyroidectomy and treated accordingly to experimental groupings. Weekly body weight changes were recorded, gastric ulcer was induced by ischemia-reperfusion and gastric acid secretion evaluated. They were sacrificed 1 hour, 3 and 7 days post ulcer induction, blood samples collected for haematological indices through cardiac puncture and their stomachs prepared for gross and microscopic examinations to assess gastric healing. Gastric tissue protein, malondialdehyde (MDA), Superoxide Dismutase (SOD), Catalase (CAT), and Nitric oxide (NO) were assessed as biomarkers of healing. Data were analysed using one way ANOVA and Student's t test with p< 0.05 considered statistically significant.Results: Thyroxine treated rats showed significant weight loss compared with NC and ThU groups. Percentage healing rate was significantly increased in thyroxine treated group compared with ThU animals by 1 hour (42.45% and -42.81%), days 3 (35.14% and -59.36%), and 7 (64.29% and -115.7%).Hematological indices significantly increased in thyroxine treated group compared with other groups. Thyroxine treatment significantly reduced Neutrophil/Lymphocyte; Platelet/NO as well as lipid peroxidation index in this study.Superoxide dismutase, CAT and NO increased significantly in thyroxine treated rats compared with other groups.Conclusion: Thyroxine treatment facilitates the healing of ischeamic-reperfused gastric ulcers possibly by increasing NO activity which in turn causes increased vasodilatation and enhanced endogenous antioxidants at the ulcer sites

Effects of Medication with Ivermectin; Chloroquine and Artemether on Plasma Nitrate / nitrite Levels in Calves Naturally Infected with Onchocerca Gutturosa

In a comparative study involving the use of Ivermectin; Chloroquine and Artemether against Onchocerca gutturosa in calves; the plasma nitrate /nitrite concentration was measured. Following treatment and clearance of skin mf of O. gutturosa; the plasma nitrate/ nitrite concentrations; nor the stable end product of Nitric Oxide (NO) breakdown; rise significantly although it showed short peaks following reduction in dermal mf counts but no clear correlation was detected

Is there no treatment for Severe Sepsis?

Sepsis is a systemic inflammatory response syndrome in the presence of suspected or proven infection; and it may progress to or encompass organ failure (severe sepsis) and hypotension (septic shock). Clinicians possess an arsenal of supportive measures to combat severe sepsis and septic shock; and some success; albeit controversial; has been achieved by using low doses of corticosteroids or recombinant human activated protein C. However; a truly effective mediator-directed specific treatment has not been developed yet. Treatment with low doses of corticosteroids or with recombinant human activated protein C remains controversial and its success very limited. Attempts to treat shock by blocking LPS; TNF or IL-1 were unsuccessful; as were attempts to use interferon-gamma or granulocyte colony stimulating factor. Inhibiting nitric oxide synthases held promise but met with considerable difficulties. Scavenging excess nitric oxide or targeting molecules downstream of inducible nitric oxide synthase; such as soluble guanylate cyclase or potassium channels; might offer other alternatives

Is there NO treatment for severe sepsis?

Sepsis is a systemic inflammatory response syndrome in the presence of suspected or proven infection; and it may progress to or encompass organ failure (severe sepsis) and hypotension (septic shock). Clinicians possess an arsenal of supportive measures to combat severe sepsis and septic shock; and some success; albeit controversial; has been achieved by using low doses of corticosteroids or recombinant human activated protein C. However; a truly effective mediator-directed specific treatment has not been developed yet. Treatment with low doses of corticosteroids or with recombinant human activated protein C remains controversial and its success very limited. Attempts to treat shock by blocking LPS; TNF or IL-1 were unsuccessful; as were attempts to use interferon-gamma or granulocyte colony stimulating factor. Inhibiting nitric oxide synthases held promise but met with considerable difficulties. Scavenging excess nitric oxide or targeting molecules downstream of inducible nitric oxide synthase; such as soluble guanylate cyclase or potassium channels; might offer other alternatives

Manipulation of nitric oxide in an animal model of acute liver injury. The impact on liver and intestinal function

Background: Nitric oxide may have a protective effect on the liver during endotoxemia and chronic inflammation. There is evidence that it maintains liver and intestinal tissue integrity during inflammatory processes. We evaluated the impact of altering nitric oxide release on acute liver injury; the associated gut injury and bacterial translocation; at different time intervals. Methods: An acute rat liver injury model induced by D-galactosamine was used. Sprague Dawley rats were divided into four main groups: normal control; acute liver injury control; acute liver injury + N-nitro-L-arginine methyl ester (L-NAME); acute liver injury + L-NAME + L-arginine. Each group was divided into three subgroups according to the different time intervals (6; 12; 24 hours) after the induction of the liver injury. Liver enzymes and bilirubin were evaluated; as well as bacterial translocation; cecal and colonic microflora; and histological study of liver; ileum and cecum. Results:Liver enzymes increased significantly at all time intervals in acute liver injury + L-NAME compared to liver injury control groups. Bacterial translocation increased significantly in liver injury + L-NAME groups; at 6 hours to the liver; at 12 hours to the liver and mesenteric lymph nodes (MLNs); and at 24 hours to arterial and portal blood; liver and MLNS. Inhibition of nitric oxide increased significantly the Enterobacteriaceae count in cecum compared to normal and liver injury control groups. The G-negative anaerobes increased significantly in the colon compared to the liver injury control group. Conclusion: Inhibition of nitric oxide in an acute liver injury model potentiates the liver injury as evidenced by increased appearance of hepatocellular necrosis and elevated liver enzymes and bilirubin. It increases the Enterobacteriaceae in both cecum and colon and G-negative anaerobes in the colon. It also increases bacterial translocation to extra-intestinal sites. The increased bacterial translocation could be one of the mechanisms potentiating liver injury and nitric oxide may be pathophysiologically involved. Further studies are required to confirm this hypothesis