Effects of hydro-ethanolic extract of leaves of Maesa lanceolata (Mursinaceae) on acetic acid-induced ulcerative colitis in rats

Inflammopharmacology - Ulcerative colitis is a form of inflammatory bowel disease that is characterized by acute and chronic inflammation. The aim of this work was to evaluate the efficacy of...     

Characterizing Blunt Use Among Twitter Users: Racial/Ethnic Differences in Use Patterns and Characteristics

Background: Young adult Twitter users are exposed to and often participate in tweets that promote risky behaviors, such as blunt use. Blunts are hollowed out cigars or cigarillos that are filled with marijuana. Objectives: The current study was designed to determine the use patterns and characteristics of African American, Hispanic and White young adult Twitter users who reported past month blunt use. Methods: Young adults (N = 753, 74% male) who reported past month blunt use were recruited via Twitter to participate in a brief anonymous online survey about their blunt use. Results: Findings revealed that African American young adults initiated blunt smoking at an earlier age (14.8 years), reported more days of blunt smoking in the past month (23.2 days) and smoked more blunts in the past month (27.2 blunts) than their Hispanic (16.5 years, 19.7 days, and 15.4 blunts) and White (18.1 years, 15.8 days, and 22.2 blunts) counterparts, p <.01. African American young adults were more likely than their White counterparts to report physical craving as an obstacle to quitting blunt smoking. Several racial/ethnic differences were also found on attitudes about blunt use and reasons for initiating and continuing to smoke blunts. Conclusions: Findings suggest that blunt use patterns and attitudes about blunt use vary by race/ethnicity. Understanding racial/ethnic differences in blunt use patterns and characteristics offers opportunities to tailor future interventions and enhance outcomes among African American, Hispanic and White young adults.     

Practical screening and early treatment of hepatocellular carcinoma. Results of a French survey

AIM: To describe French practices for screening hepatocellular carcinoma. METHODS: A standardized questionnaire was mailed to all French hospital hepato-gastroenterologists in June 1999. RESULTS: 411 out of 623 practitioners responded (66%). 394 (96%) routinely screen hepatocellular carcinoma, mainly with ultrasound (98%) and mainly at 6-month intervals (77%). Screening was performed in cirrhosis (100%) or extensive fibrosis (54%), independent of the etiology (21%) or the Child-Pugh score of the chronic liver disease (41%), but based on age and treatment feasibility. If of a small hypoechogenic nodule was detected in a young patient with compensated HCV-cirrhosis, 59% of practitioners performed a histological examination. In case of non biopsy-proven hepatocellular carcinoma, a second biopsy (49%), treatment (either percutaneous alcohol injection, resection or transplantation) (24%) or an ultrasonographic follow-up (23%) was proposed. In case of biopsy-proven hepatocellular carcinoma, resection (49%), transplantation (30%) or percutaneous alcohol injection (16%) was proposed. CONCLUSION: Almost all French specialists routinely screen cirrhotic patients for hepatocellular carcinoma, but use somewhat different modalities. In case of small HCC without contraindications to curative treatment, surgical resection is performed in half the patients.     

Linking supply to demand: the neuronal monocarboxylate transporter MCT2 and the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid receptor GluR2/3 subunit are associated in a common trafficking process

MCT2 is the major neuronal monocarboxylate transporter (MCT) that allows the supply of alternative energy substrates such as lactate to neurons. Recent evidence obtained by electron microscopy has demonstrated that MCT2, like α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, is localized in dendritic spines of glutamatergic synapses. Using immunofluorescence, we show in this study that MCT2 colocalizes extensively with GluR2/3 subunits of AMPA receptors in neurons from various mouse brain regions as well as in cultured neurons. It also colocalizes with GluR2/3-interacting proteins, such as C-kinase-interacting protein 1, glutamate receptor-interacting protein 1 and clathrin adaptor protein. Coimmunoprecipitation of MCT2 with GluR2/3 and C-kinase-interacting protein 1 suggests their close interaction within spines. Parallel changes in the localization of both MCT2 and GluR2/3 subunits at and beneath the plasma membrane upon various stimulation paradigms were unraveled using an original immunocytochemical and transfection approach combined with three-dimensional image reconstruction. Cell culture incubation with AMPA or insulin triggered a marked intracellular accumulation of both MCT2 and GluR2/3, whereas both tumor necrosis factor α and glycine (with glutamate) increased their cell surface immunolabeling. Similar results were obtained using Western blots performed on membrane or cytoplasm-enriched cell fractions. Finally, an enhanced lactate flux into neurons was demonstrated after MCT2 translocation on the cell surface. These observations provide unequivocal evidence that MCT2 is linked to AMPA receptor GluR2/3 subunits and undergoes a similar translocation process in neurons upon activation. MCT2 emerges as a novel component of the synaptic machinery putatively linking neuroenergetics to synaptic transmission.     

Brain glucagon-like peptide-1 regulates arterial blood flow, heart rate, and insulin sensitivity

OBJECTIVE— To ascertain the importance and mechanisms underlying the role of brain glucagon-like peptide (GLP)-1 in the control of metabolic and cardiovascular function. GLP-1 is a gut hormone secreted in response to oral glucose absorption that regulates glucose metabolism and cardiovascular function. GLP-1 is also produced in the brain, where its contribution to central regulation of metabolic and cardiovascular homeostasis remains incompletely understood.RESEARCH DESIGN AND METHODS— Awake free-moving mice were infused with the GLP-1 receptor agonist exendin-4 (Ex4) into the lateral ventricle of the brain in the basal state or during hyperinsulinemic eu-/hyperglycemic clamps. Arterial femoral blood flow, whole-body insulin-stimulated glucose utilization, and heart rates were continuously recorded.RESULTS— A continuous 3-h brain infusion of Ex4 decreased femoral arterial blood flow and whole-body glucose utilization in the awake free-moving mouse clamped in a hyperinsulinemic-hyperglycemic condition, only demonstrating that this effect was strictly glucose dependent. However, the heart rate remained unchanged. The metabolic and vascular effects of Ex4 were markedly attenuated by central infusion of the GLP-1 receptor (GLP-1R) antagonist exendin-9 (Ex9) and totally abolished in GLP-1 receptor knockout mice. A correlation was observed between the metabolic rate and the vascular flow in control and Ex4-infused mice, which disappeared in Ex9 and GLP-1R knockout mice. Moreover, hypothalamic nitric oxide synthase activity and the concentration of reactive oxygen species (ROS) were also reduced in a GLP-1R–dependent manner, whereas the glutathione antioxidant capacity was increased. Central GLP-1 activated vagus nerve activity, and complementation with ROS donor dose-dependently reversed the effect of brain GLP-1 signaling on peripheral blood flow.CONCLUSIONS— Our data demonstrate that central GLP-1 signaling is an essential component of circuits integrating cardiovascular and metabolic responses to hyperglycemia.There is now compelling evidence supporting the interplay between metabolic and vascular diseases (1,2) in which neuronal circuits in the central nervous system seem to play a critical role in orchestrating the control of glucose homeostasis (3). We recently demonstrated that the central infusion of insulin decreased blood pressure and increased arterial blood flow and heart rate through a molecular mechanism depending on the synthesis of nitric oxide in the hypothalamus (4). Importantly, the central regulation of nitric oxide (NO) metabolism affected whole-body glucose utilization (5). This mechanism was impaired during high-fat diet–induced insulin resistance and diabetes and reverted upon central NO supplementation (4). These findings raise the possibility that signals from peripheral tissues, which act on the brain to control glucose metabolism, could also regulate vascular function.Enteroendocrine cells have important roles in regulating energy intake and glucose homeostasis through their actions on peripheral target organs, including the endocrine pancreas. Enteroendocrine cells secrete multiple hormones, including glucagon-like peptide (GLP)-1, which controls pancreatic endocrine secretion (6). GLP-1 is also a neuropeptide synthesized by neurons in the caudal regions of the nucleus of the solitary tract (NTS) (7,8). GLP-1 is released into the hypothalamus and controls food intake, blood pressure, and heart rate (9,10). Whereas most of the glucose-lowering actions of GLP-1 have been attributed to the direct effect of the hormone on the endocrine pancreas, i.e., to stimulation of insulin and inhibition of glucagon secretion, we demonstrated the importance of extra-pancreatic GLP-1 receptor–dependent control of insulin secretion (11) and whole-body glucose distribution (12). The infusion into the brain of the GLP-1 receptor antagonist exendin-9 (Ex9) inhibited insulin secretion induced by gut glucose (11). Conversely, central administration of the GLP-1 receptor agonist exendin-4 (Ex4) augmented intravenous glucose-stimulated insulin secretion to a level similar to that obtained during an intragastric glucose infusion (11). Our data suggested that the absorptive state was associated with the stimulation of the gut-to-brain axis leading to the activation of brain GLP-1 signaling and, consequently, to hyperinsulinemia. During the absorptive state, blood flow redistribution toward mesenteric organs is also observed, which has been proposed to favor nutrient redistribution into the liver (13). Importantly, stimulation of the central GLP-1 receptor increases blood pressure and heart rate and activates autonomic regulatory neurons (8,14,15). However, recently it has been shown that GLP-1 reduced islet blood flow after glucose administration (16). Therefore, the role of brain GLP-1 signaling also in the control of cardiovascular homeostasis remains incompletely understood.We have now pursued the importance of GLP-1 action in the central nervous system for control of cardiovascular function using studies in conscious free-moving mice. After central GLP-1 infusion, we simultaneously recorded femoral arterial blood flow, heart rate, and insulin and glucose sensitivity during hyperinsulinemic-euglycemic or hyperglycemic clamps. We now demonstrate that hypothalamic reactive oxygen and nitrogen species are controlled by brain GLP-1 and are essential for the coordinated regulation of metabolic and cardiovascular function.     

Comparison of nebulized epinephrine and terbutaline in patients with acute severe asthma: a controlled trial

PURPOSE: To compare the efficacy and tolerability of nebulized adrenaline and terbutaline in acute severe asthma. METHODS: Design: Prospective pilot randomized double-blind cross-over trial. Setting: Emergency department of a university hospital. Patients: Thirty-eight patients admitted with severe acute asthma. Each patient received adrenaline (3 mg) and terbutaline (5 mg) nebulizations over 20 min in randomized order. Additional treatment comprised methylprednisolone, intravenous hydration, and oxygen. The efficacy and tolerability of the two drugs were evaluated at the end of each nebulization as well as potential synergistic effects. RESULTS: Eighteen patients received adrenaline first, and 20 received terbutaline first. Peak expiratory flow (PEF) improved significantly in both groups after the first nebulization (from 157 L/min +/- 111 L/min to 199 L/min +/- 134 L/min with adrenaline, P <.01; and from 142 L/min +/- 65 L/min to 193 L/min +/- 181 L/min with terbutaline, P <.01). Both drugs induced a significant decrease in respiratory frequency. The improvement in PaO2 was only significant with terbutaline. Respiratory frequency, PEF and PaO2 were not improved by the second nebulization. No adverse effects were observed. CONCLUSIONS: Adrenaline nebulization was as effective and as well tolerated as terbutaline in acute severe asthma. No synergistic effect between terbutaline and adrenaline was observed.     

Risk factors analysis for Pneumocystis jiroveci pneumonia (PCP) in patients with haematological malignancies and pneumonia

A retrospective matched case-control investigation was conducted to assess risk factors suggesting Pneumocystis jiroveci pneumonia (PCP) when pneumonia occurs in adult patients with haematological malignancies. Cases and controls included were HIV-negative, presented with pneumonia and had benefited from a bronchoalveolar lavage (BAL). The presence of Pneumocystis jiroveci cysts was systematically investigated by cytochemical staining and/or immunofluorescence. Cases were patients with Pneumocystis jiroveci cysts isolated on BAL fluid (n = 31, mean age 51+/-14 y; range 20-73 y). Controls were patients without Pneumocystis jiroveci cysts (n = 62, mean age 54+/-13 y; range 25-75 y) and were matched to case patients by age and y of pneumonia diagnosis. Statistical analysis indicated that the following factors were associated with PCP: vincristine (p = 0.009, odds ratio (OR) =2.11, 95% confidence interval (CI): 1.19-3.72), a daily corticosteroid therapy for more than 1 month (p = 0.05) during the past y, and a lymphocyte count less than 0.5 x 10(9)/l on the d of pneumonia diagnosis (p = 0.04). Clinicians should be aware, in order to evoke this diagnosis when pneumonia occurs in patients with these risk factors. The goal of this exploratory study was to identify risk factors that could eventually be further investigated by a larger prospective multicentre study.