WHAT'S KNOWN ON THIS SUBJECT:Neuronal apoptosis that follows hypoxia-ischemia is triggered by upregulation of NO synthase, with excessive accumulation of NO and release of excitatory amino acids such as glutamate. Animal studies demonstrated the ability of erythropoietin to attenuate these mechanisms. WHAT THIS STUDY ADDS:The administration of erythropoietin to infants with asphyxia with mild/moderate HIE was associated with favorable decreases in endogenous NO production, decreases in seizure activity, and improved neurodevelopmental outcomes to 6 months of age. abstract OBJECTIVE: The goal was to examine biochemical, neurophysiologic, anatomic, and clinical changes associated with erythropoietin administration to neonates with hypoxic-ischemic encephalopathy (HIE). METHODS:We conducted a prospective case-control study with 45 neonates in 3 groups, a normal healthy group (N ϭ 15), a HIEerythropoietin group (N ϭ 15; infants with mild/moderate HIE who received human recombinant erythropoietin, 2500 IU/kg, subcutaneously, daily for 5 days), and a HIE-control group (N ϭ 15; did not receive erythropoietin). Serum concentrations of nitric oxide (NO) were measured at enrollment for the normal healthy neonates and at enrollment and after 2 weeks for the 2 HIE groups. The 2 HIE groups underwent electroencephalography at enrollment and at 2 to 3 weeks. Brain MRI was performed at 3 weeks. Neurologic evaluations and Denver Developmental Screening Test II assessments were performed at 6 months. RESULTS:Compared with normal healthy neonates, the 2 HIE groups had greater blood NO concentrations (P Ͻ .001). At enrollment, the 2 HIE groups did not differ in clinical severity, seizure incidence, NO concentrations, or electroencephalographic findings. At 2 weeks of age, electroencephalographic backgrounds improved significantly (P ϭ .01) and NO concentrations decreased (P Ͻ .001) in the HIEerythropoietin group, compared with the HIE-control group; MRI findings did not differ between groups. At 6 months of age, infants in the HIE-erythropoietin group had fewer neurologic (P ϭ .03) and developmental (P ϭ .03) abnormalities. CONCLUSION:This study demonstrates the feasibility of early administration of human recombinant erythropoietin to term neonates with HIE, to protect against encephalopathy.

No abstract

Gastric ulcer is a very common gastrointestinal disease that may lead to dangerous complications and even death. This study was conducted to evaluate the prophylactic effect of nebivolol against indomethacin [INDO]-induced gastric ulcer. Male Wistar rats were divided into four groups: normal control, ulcer control (INDO only), omeprazole before INDO and nebivolol before INDO. Each rat to receive nebivolol and omeprazole was given the agent orally (by gavage) daily for 10 days prior to induction of ulcer by oral dosing with INDO. Four hours after INDO treatment, all rats were euthanized and their stomachs obtained for measures of gastric acidity, oxidative stress and inflammatory markers, as well as cytoprotective mediators. The results showed that a single oral dose of INDO (100 mg/kg) induced gastric acidity, an ulcer index of 2900 and significantly increased levels of gastric tumor necrosis factor (TNF)-α and malondialdehyde (MDA) and significantly decreased levels of gastric prostaglandin E2 (PGE2), glutathione (GSH) and nitric oxide (NO), compared to in normal control counterpart stomachs. Giving nebivolol before INDO corrected the gastric acidity and resulted in a significant increase in GSH, PGE2 and NO and a significant decrease in TNFα and MDA gastric levels, compared to ulcer control values. Results obtained with nebivolol were comparable to those with omeprazole; the preventive index in the nebivolol group was 90.7% compared to 94.5% in rats in the omeprazole group. These studies showed that nebivolol provided a valuable role in preventing gastric ulcers induced by INDO and provided a promise for potentially protecting hypertensive patients from experiencing gastric ulcer. Thus, it is possible that, pending further studies, nebivolol could be used for pre-exposure prophylaxis from gastric ulcer in these patients.

Since the incidence of breast cancer increases dramatically all over the world, the search for effective treatment is an urgent need. Metformin has demonstrated anti-tumorigenic effect both in vivo and in vitro in different cancer types. This work was designed to examine on molecular level the mode of action of metformin in mice bearing solid Ehrlich carcinoma and to evaluate the use of metformin in conjunction with doxorubicin as a combined therapy against solid Ehrlich carcinoma. Ehrlich ascites carcinoma cells were inoculated in 60 female mice as a model of breast cancer. The mice were divided into four equal groups: Control tumor, metformin, doxorubicin, and co-treatment. Metformin (15 mg/kg) and doxorubicin (4 mg/kg) were given intraperitoneally (i.p.) for four cycles every 5 days starting on day 12 of inoculation. The anti-tumorigenic effect of metformin was mediated by enhancement of adenosine monophosphate protein kinase activity and elevation of P53 protein as well as the suppression of nuclear factor-kappa B, DNA contents, and cyclin D1 gene expression. Metformin and doxorubicin mono-treatments exhibited opposing action regarding cyclin D1 gene expression, phosphorylated adenosine monophosphate protein kinase, and nuclear factor-kappa B levels. Co-treatment markedly decreased tumor volume, increased survival rate, and improved other parameters compared to doxorubicin group. In parallel, the histopathological findings demonstrated enhanced apoptosis and absence of necrosis in tumor tissue of co-treatment group. Metformin proved chemotherapeutic effect which could be mediated by the activation of adenosine monophosphate protein kinase and related pathways. Combining metformin and doxorubicin, which exhibited different mechanisms of action, produced greater efficacy as anticancer therapeutic regimen.

No abstract

Captopril treatment showed a protective and comparable effect with MP treatment in AP rat model.

Workers exposed to benzene frequently suffer from toxicities of the bone marrow as well as the central nervous, immune, and reproductive systems. This toxicity most likely is a result of the oxidative metabolism of benzene to reactive products. As green tea possesses antioxidant effects, the objective of this study was to examine any amelioration of benzene-induced oxidative stress in pump workers drinking 6 cups (150 ml/cup) of freshly prepared tea daily. Sixty male non-smoking subjects, divided into four groups: no benzene exposure/no green tea; no exposure/tea; exposure/no tea; and, exposure/tea, were monitored after a 6 mo period. On the final day of the study, urine samples were collected for analyses of benzene, trans-trans muconic acid, and phenol. Blood was also collected at this time; plasma was assayed for total antioxidant activity, malondialdehyde (MDA), and glutathione (GSH) while erythrocytes were analyzed for activity of antioxidant enzymes glutathione peroxidase (GSHPX), superoxide dismutase (SOD), and catalase. The results demonstrated that urinary levels of benzene, trans-trans muconic acid, and phenol were elevated in all pump workers, and that this elevation was mitigated by consumption of green tea. The benzene exposures also led to significant reductions in plasma GSH levels and erythrocyte antioxidant enzyme activities; these effects were abrogated (to near-control levels) by the tea. Interestingly, among control subjects, tea ingestion itself caused significant increases in both GSHPX and catalase activities. Unlike with the other plasma parameters, while the benzene exposures also significantly increased plasma MDA levels and decreased total antioxidant activity, tea ingestion did not cause a near-total reversion to control values; the effects on these two endpoints were more like those noted with the urine parameters (mitigation, not abrogation). These studies demonstrate that drinking green tea during benzene exposure can reduce several parameters indicative of oxidative stress. As such, as a dietary supplement, green tea could represent a potential therapeutic agent in reducing certain aspects of benzene-induced toxicity.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality after lung and stomach cancers. This work was undertaken to investigate some of the biochemical mediators/pathways associated with or implicated in the pathogenesis of HCC. Male albino mice were classified into two groups: normal control group and HCC group. Early stage HCC was induced by injection of diethylnitrosamine (DEN) i.p. 200 mg/kg as a single dose, and after 2 weeks, the mice were given i.p. injection of thioacetamide (TAA) 100 mg/kg twice per week for 4 weeks. Mice were left for further 2 weeks without any treatment, after which, mice were sacrificed; blood and liver samples were collected. Serum was used for determination of activities of glucose-6-phosphate dehydrogenase (G6PDH) and aldolase as well as levels of insulin-like growth factor-1 (IGF-1) and epithelial cadherin (E-cadherin). One portion of the liver was used for histopathological examination and immunohistochemical staining of the tumor suppressor p53 protein. Another portion of the liver was used for determination of citrate synthase activity. Induction of HCC in mice resulted in significant increase in G6PDH and aldolase activities, and E-cadherin level, but significant decrease in IGF-1. HCC mice group showed moderate expression of p53 protein. These results suggest that the molecular pathogenesis of HCC in mice involves reduction of serum level of IGF-1 and increased serum level of E-cadherin accompanied by dysregulation of p53 protein expression. HCC was also associated with reprogrammed metabolic profile shifted toward increased glycolysis and lipogenesis.