Effects of exposure to cigarette smoke on intestinal propulsion in rats.

The effects of acute exposure to cigarette smoke and systemic administration of nicotine on intestinal propulsion were investigated in rats. The propulsive activity was measured as migration of charcoal powder in the intestine. This activity was suppressed by acute exposure (10 min) to cigarette smoke and by nicotine (0.5 mg/kg x 2, s.c.) administration. This intestinal suppression was more marked in the rats given nicotine than in those exposed to cigarette smoke, whereas the plasma concentrations of nicotine in both rats were similar. These results suggest that acute exposure to cigarette smoke and nicotine administration delay gastric emptying and/or suppress intestinal propulsion, and that some components other than nicotine contained in cigarette smoke may attenuate the suppression of intestinal propulsion induced by nicotine.</p

The effect of immobilization stress on the pharmacokinetics of omeprazole in rats.

The effects of immobilization stress on the pharmacokinetics of omeprazole were studied in rats. The immobilization stress for 30 or 60 min immediately after oral administration of the drug caused an increase in the time to reach the maximum concentration. However, such stress did not alter the area under the plasma concentration-time curve (AUC). When administered intravenously, the half-life during the elimination phase was significantly prolonged by 30 min of immobilization stress, but the AUC value remained unchanged. The intestinal propulsive activity was significantly decreased by immobilization stress. These findings suggest that immobilization stress reduces gastrointestinal motility. A resulting delay during the absorption phase of omeprazole occurs, although the degree of influence on overall pharmacokinetics is relatively insignificant.</p

Neonatal asphyxia as an inflammatory disease: Reactive oxygen species and cytokines

Neonatologists resuscitate asphyxiated neonates by every available means, including positive ventilation, oxygen therapy, and drugs. Asphyxiated neonates sometimes present symptoms that mimic those of inflammation, such as fever and edema. The main pathophysiology of the asphyxia is inflammation caused by hypoxic-ischemic reperfusion. At birth or in the perinatal period, neonates may suffer several, hypoxic insults, which can activate inflammatory cells and inflammatory mediator production leading to the release of larger quantities of reactive oxygen species (ROS). This in turn triggers the production of oxygen stress-induced high mobility group box-1 (HMGB-1), an endogenous damage-associated molecular patterns (DAMPs) protein bound to toll-like receptor (TLR) -4, which activates nuclear factor-kappa B (NF-κB), resulting in the production of excess inflammatory mediators. ROS and inflammatory mediators are produced not only in activated inflammatory cells but also in non-immune cells, such as endothelial cells. Hypothermia inhibits pro-inflammatory mediators. A combination therapy of hypothermia and medications, such as erythropoietin and melatonin, is attracting attention now. These medications have both anti-oxidant and anti-inflammatory effects. As the inflammatory response and oxidative stress play a critical role in the pathophysiology of neonatal asphyxia, these drugs may contribute to improving patient outcomes

Relevance of the Core 70 and IL-28B polymorphism and response-guided therapy of peginterferon alfa-2a ± ribavirin for chronic hepatitis C of Genotype 1b: a multicenter randomized trial, ReGIT-J study

BACKGROUND: We conducted a multicenter randomized clinical trial to determine the optimal treatment strategy against chronic hepatitis C virus (HCV) with genotype 1b and a high viral load (G1b/high). METHODS: The study subjects included 153 patients with G1b/high. Patients were initially treated with PEG-IFNα-2a alone and then randomly assigned to receive different treatment regimens. Ribavirin (RBV) was administered to all patients with HCV RNA at week 4. Patients negative for HCV RNA at week 4 were randomly assigned to receive PEG-IFNα-2a (group A) or PEG-IFNα-2a/RBV (group B). Patients who showed HCV RNA at week 4 but were negative at week 12 were randomly assigned to receive weekly PEG-IFNα-2a (group C) or biweekly therapy (group D). Patients who showed HCV RNA at week 12 but were negative at week 24 were randomly assigned to receive PEG-IFNα-2a/RBV (group E) or PEG-IFNα-2a/RBV/fluvastatin (group F). RESULTS: Overall, the rate of sustained virological response (SVR) was 46 % (70/153). The total SVR rate in the group (A, D, and F) of response-guided therapy was significantly higher than that in the group (B, C, and E) of conventional therapy [70 % (38/54) versus 52 % (32/61), p = 0.049]. Although IL28-B polymorphism and Core 70 mutation were significantly associated with efficacy, patients with rapid virological response (RVR) and complete early virological response (cEVR) achieved high SVR rates regardless of their status of IL-28B polymorphism and Core 70 mutation. CONCLUSION: In addition to knowing the IL-28B polymorphism and Core 70 mutation status, understanding the likelihood of virological response during treatment is critical in determining the appropriate treatment strategy