Effects of vasopressin and involvement of receptor subtypes in the rat central amygdaloid nucleus in vitro

Effects of arginine-vasopressin (AVP) on neurons in the central amygdaloid nucleus (ACe) were investigated with rat brain slice preparations using extracellular recording methods. Of 160 ACe neurons tested, 70 cells (44%) were excited and 9 cells (6%) were inhibited by bath application of AVP at 3 x 10(-7) M. The excitatory effects of AVP were dose-dependent and the threshold concentration was approximately 10(-10) to 10(-9) M. The excitatory effects of AVP persisted under blockade of synaptic transmission by perfusing with Ca2+-free and high-Mg2+ medium, whereas the inhibitory effects were abolished by synaptic blockade. AVP-induced effects were mimicked by a V1-receptor agonist and completely blocked by a selective V1-antagonist. V2-agonist produced no effects on ACe neurons and V2-antagonist had no effect on AVP-induced excitation. These results showed that the excitatory effect of AVP on ACe neurons was produced by a direct action through the V1-receptors, whereas the inhibitory response of ACe neurons to AVP seemed to be produced by an indirect action. The results of this study suggest that AVP is involved in the amygdala-relevant functions as a neurotransmitter or a neuromodulator.     

Inflammatory mediator and organ dysfunction syndrome

PURPOSE: To assess the role of serum folate in the risk for coronary heart disease in a national cohort of US adults. METHODS: Data from the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (N = 1921) were used to determine whether a low serum folate concentration was associated with an increased risk for incident coronary heart disease (N = 284). The Cox proportional hazards model adjusted for age, sex, race, education, serum cholesterol, systolic blood pressure, body mass index, cigarette smoking, and alcohol consumption. RESULTS: The association between folate and risk for coronary heart disease differed by age group (p = 0.03). Among persons aged 35-55 years, the relative risk for heart disease was 2.4 (95% confidence interval (CI), 1.1-5.2) for persons in the lowest quartile (< or = 9.9 nmol/L) when compared with those in the highest quartile (> or = 21.8 nmol/L). However, among persons > or = 55 years the relative risk was 0.5 (95% CI, 0.3-0.8) for comparisons of the lowest versus highest quartiles. CONCLUSIONS: If the age differences in the risk for heart disease are confirmed, randomized clinical trials assessing the role of folic acid for the prevention of heart disease may need to include young adults in order to demonstrate benefits related to folate supplementation.     

Hepatocyte nuclear factor-4 alpha gene mutations in Japanese non-insulin dependent diabetes mellitus (NIDDM) patients

OBJECTIVE: To assess the effect of pregnancy, maternal position, and cardiac output on intrapulmonary shunting (Qs/Qt) in normotensive nulliparous women near term. METHODS: Ten normotensive nulliparas between 36 and 38 weeks' gestation underwent pulmonary artery catheterization (via the subclavian route) and radial artery canalization. Baseline assessments were made with subjects in the left lateral recumbent position after a 30-minute stabilization period. Measurements were obtained sequentially in the left lateral, right lateral, supine, knee-chest, sitting, and standing positions. Each position change was followed by a 10-minute pre-measurement stabilization period. Cardiac output was measured via the thermodilution technique. Blood samples were obtained simultaneously from the pulmonary and radial arteries and analyzed in duplicate for oxygen content with a blood gas analyzer. Qs/Qt was calculated using the classic shunt equation. Statistical analysis was performed by analysis of variance of repeated measures of Qs/Qt and maternal position. The relationship of Qs/Qt to maternal cardiac output was evaluated by the correlation coefficient. Significance was defined as P < .05. RESULTS: Directly measured Qs/Qt averaged 15.3% in left lateral, 15.2% in right lateral, 13.9% in supine, 12.8% in knee-chest, 13.8% in sitting, and 13.0% in standing positions. There was no statistically significant correlation between Qs/Qt and cardiac output (R2 = 0.11, not significant). CONCLUSION: This is the first report of directly measured Qs/Qt in normal pregnant women in the third trimester. Qs/Qt values reported in pregnancy are higher than those reported in nonpregnant individuals.     

Two kinds of adsorbed N atoms with different reactivities with H2 on a Pt0.25Rh0.75(100) surface

Two kinds of adsorbed N atoms exist on a Pt_0.25Rh_0.75(100) surface. One desorbs at 490 K and the other desorbs at 650 K. The former reacts with H₂ at 400 K, but the latter does not. It is supposed that the adsorption of these two N atoms is responsible of the surface composition, ratio of Pt and Rh. This revised version was published online in July 2006 with corrections to the Cover Date.     

Neurosecretory Protein GL Accelerates Liver Steatosis in Mice Fed Medium-Fat/Medium-Fructose Diet

Sugar consumption can readily lead to obesity and metabolic diseases such as liver steatosis. We previously demonstrated that a novel hypothalamic neuropeptide, neurosecretory protein GL (NPGL), promotes fat accumulation due to the ingestion of sugar by rats. However, differences in lipogenic efficiency of sugar types by NPGL remain unclear. The present study aimed to elucidate the obesogenic effects of NPGL on mice fed different sugars (i.e., sucrose or fructose). We overexpressed the NPGL-precursor gene (Npgl) in the hypothalamus of mice fed a medium-fat/medium-sucrose diet (MFSD) or a medium-fat/medium-fructose diet (MFFD). Food intake and body mass were measured for 28 days. Body composition and mRNA expression of lipid metabolic factors were measured at the endpoint. Npgl overexpression potently increased body mass with fat accumulation in the white adipose tissue of mice fed MFFD, although it did not markedly affect food intake. In contrast, we observed profound fat deposition in the livers of mice fed MFFD but not MFSD. In the liver, the mRNA expression of glucose and lipid metabolic factors was affected in mice fed MFFD. Hence, NPGL induced liver steatosis in mice fed a fructose-rich diet.     

Removal of endotoxin and cytokines by plasma exchange in patients with acute hepatic failure

OBJECTIVES: To compare the circulating concentrations of endotoxin and cytokines in patients with fulminant hepatitis and patients with the severe form of acute hepatitis, and to assess the effects of plasma exchange on the circulating concentrations of these inflammatory mediators in patients with acute hepatic failure. DESIGN: Prospective, consecutive entry study of patients meeting fulminant hepatitis criteria and the severe form of acute hepatitis criteria. SETTING: University hospital, intensive care unit. PATIENTS: Five patients with fulminant hepatitis, eight patients with the severe form of acute hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. INTERVENTIONS: Plasma endotoxin, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were determined on admission in five patients with fulminant hepatitis and eight patients with the severe form of acute hepatitis. Circulating concentrations of the inflammatory mediators were measured before and after a single course of plasma exchange in eight patients with acute liver failure, including five patients with fulminant hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. MEASUREMENTS AND MAIN RESULTS: TNF-alpha and IL-6 in patients with fulminant hepatitis were significantly higher than in patients with the severe form of acute hepatitis, whereas endotoxin concentrations did not differ between patients with fulminant hepatitis or the severe form of acute hepatitis. IL-1beta was not detectable in patients with either fulminant hepatitis or the severe form of acute hepatitis. Plasma endotoxin concentrations decreased immediately after plasma exchange. Serum concentrations of TNF-alpha and IL-6 were significantly lower after plasma exchange than before plasma exchange. CONCLUSION: TNF-alpha and IL-6 may be important in the pathogenesis of the clinical symptoms that differentiate fulminant hepatitis from the severe form of acute hepatitis, and plasma exchange removes these inflammatory mediators from the circulation of patients with severe liver disease.     

Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic cytokine that induces cancer cell death by binding to TRAIL receptors. Because of its selective cytotoxicity toward cancer cells, TRAIL therapeutics, such as recombinant TRAIL and agonistic antibodies targeting TRAIL receptors, have garnered attention as promising cancer treatment agents. However, many cancer cells acquire resistance to TRAIL-induced cell death. To overcome this issue, we searched for agents to sensitize cancer cells to TRAIL-induced cell death by screening a small-molecule chemical library consisting of diverse compounds. We identified a cardiac glycoside, proscillaridin A, as the most effective TRAIL sensitizer in colon cancer cells. Proscillaridin A synergistically enhanced TRAIL-induced cell death in TRAIL-sensitive and -resistant colon cancer cells. Additionally, proscillaridin A enhanced cell death in cells treated with TRAIL and TRAIL sensitizer, the second mitochondria-derived activator of caspase mimetic. Proscillaridin A upregulated TRAIL receptor expression, while downregulating the levels of the anti-cell death molecules, cellular FADD-like IL-1β converting enzyme-like inhibitor protein and Mcl1, in a cell type-dependent manner. Furthermore, proscillaridin A enhanced TRAIL-induced cell death partly via O-glycosylation. Taken together, our findings suggest that proscillaridin A is a promising agent that enhances the anti-cancer efficacy of TRAIL therapeutics.