Nicotine and smoking do not decrease basal gastric mucosal blood flow in anesthetized rats

The literature regarding the effect of nicotine and cigarette smoke on gastric blood flow is conflicting. The hydrogen gas clearance technique was used to measure the effects of nicotine and cigarette smoke on basal gastric mucosal blood flow in anesthetized rats. Blood flow was measured before, during, and after treatment with either intravenous nicotine (4 or 40 μg/kg/min) or inhaled cigarette smoke (nicotine or nicotine free). Neither intravenous nicotine nor cigarette smoke significantly altered gastric mucosal blood flow. On the other hand, hypotension produced by hemorrhage significantly decreased mucosal blood flow ( P <0.05). Thus the technique used could detect a decrease in blood flow. These findings indicate that in the anesthetized rats, hypotension but not intravenous nicotine or cigarette smoke, in the doses given, reduce gastric mucosal blood flow.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44399/1/10620_2005_Article_BF01320320.pd

A hydraulically driven colonoscope

BACKGROUND: Conventional colonoscopy requires a high degree of operator skill and is often painful for the patient. We present a preliminary feasibility study of an alternative approach where a self-propelled colonoscope is hydraulically driven through the colon. METHODS: A hydraulic colonoscope which could be controlled manually or automatically was developed and assessed in a test bed modelled on the anatomy of the human colon. A conventional colonoscope was used by an experienced colonoscopist in the same test bed for comparison. Pressures and forces on the colon were measured during the test. RESULTS: The hydraulic colonoscope was able to successfully advance through the test bed in a comparable time to the conventional colonoscope. The hydraulic colonoscope reduces measured loads on artificial mesenteries, but increases intraluminal pressure compared to the colonoscope. Both manual and automatically controlled modes were able to successfully advance the hydraulic colonoscope through the colon. However, the automatic controller mode required lower pressures than manual control, but took longer to reach the caecum. CONCLUSIONS: The hydraulic colonoscope appears to be a viable device for further development as forces and pressures observed during use are comparable to those used in current clinical practice

The acute effects of a lunch containing capsaicin on energy and substrate utilisation, hormones, and satiety

BACKGROUND: Addition of capsaicin to the diet has been shown to increase satiety and thermogenesis. The effects of capsaicin on ghrelin, peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), in relation to changes in hunger and satiety are unknown. AIM: To test the acute effects of a lunch containing capsaicin on gut derived hormones (GLP-1, ghrelin, and PYY), energy expenditure (EE), substrate oxidation and satiety at lunch in the postprandial state. METHODS: Thirty subjects (age: 31 +/- 14 years, BMI: 23.8 +/- 2.8 kg/m(2)) were studied twice in a crossover design. After 30 min resting on a bed, resting metabolic rate was measured by a ventilated hood system. Subsequently lunch (35% of daily energy intake) was served. The two lunch conditions were: (1) lunch without capsaicin and (2) lunch with capsaicin (CAPS). The macronutrient composition (energy percentage) of the lunches was 60% carbohydrates, 10% protein and 30% fat. During 3 h after the lunch diet-induced thermogenesis was measured. Furthermore, anchored 100 mm visual analogue scales on the appetite profile were collected (t = 0, 30, 60, 120, 150, 180 and 240) and blood samples were taken for analysis of GLP-1, PYY, and ghrelin concentrations (t = 0, 45, 60, 120, and 180). RESULTS: Satiety and EE were not different after CAPS lunch as compared to the control lunch. Fifteen minutes after lunch CAPS lunch increased GLP-1 (p < 0.05) and tended to decrease ghrelin (p = 0.07) as compared to the control lunch. PYY responses were not different between the CAPS lunch and the control lunch. CONCLUSIONS: An acute lunch containing capsaicin had no effect on satiety, EE, and PYY, but increased GLP-1 and tended to decrease ghrelin

NS3 protease from flavivirus as a target for designing antiviral inhibitors against dengue virus

The development of novel therapeutic agents is essential for combating the increasing number of cases of dengue fever in endemic countries and among a large number of travelers from non-endemic countries. The dengue virus has three structural proteins and seven non-structural (NS) proteins. NS3 is a multifunctional protein with an N-terminal protease domain (NS3pro) that is responsible for proteolytic processing of the viral polyprotein, and a C-terminal region that contains an RNA triphosphatase, RNA helicase and RNA-stimulated NTPase domain that are essential for RNA replication. The serine protease domain of NS3 plays a central role in the replicative cycle of dengue virus. This review discusses the recent structural and biological studies on the NS2B-NS3 protease-helicase and considers the prospects for the development of small molecules as antiviral drugs to target this fascinating, multifunctional protein

Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells

<p>Abstract</p> <p>Background</p> <p>In addition to their well-documented ocular therapeutic effects, glucocorticoids (GCs) can cause sight-threatening side-effects including ocular hypertension presumably via morphological and biochemical changes in trabecular meshwork (TM) cells. In the present study, we directly compared the glucocorticoid receptor (GR) potency for dexamethasone (DEX), fluocinolone acetonide (FA) and triamcinolone acetonide (TA), examined the expression of known GRα and GRβ isoforms, and used gene expression microarrays to compare the effects of DEX, FA, and TA on the complete transcriptome in two primary human TM cell lines.</p> <p>Methods</p> <p>GR binding affinity for DEX, FA, and TA was measured by a cell-free competitive radio-labeled GR binding assay. GR-mediated transcriptional activity was assessed using the GeneBLAzer beta-lactamase reporter gene assay. Levels of GRα and GRβ isoforms were assessed by Western blot. Total RNA was extracted from TM 86 and TM 93 cells treated with 1 μM DEX, FA, or TA for 24 hr and used for microarray gene expression analysis. The microarray experiments were repeated three times. Differentially expressed genes were identified by Rosetta Resolver Gene Expression Analysis System.</p> <p>Results</p> <p>The GR binding affinity (IC₅₀) for DEX, FA, and TA was 5.4, 2.0, and 1.5 nM, respectively. These values are similar to the GR transactivation EC₅₀of 3.0, 0.7, and 1.5 nM for DEX, FA, and TA, respectively. All four GRα translational isoforms (A-D) were expressed in TM 86 and TM 93 total cell lysates, however, the C and D isoforms were more highly expressed relative to A and B. All four GRβ isoforms (A-D) were also detected in TM cells, although GRβ-D isoform expression was lower compared to that of the A, B, or C isoforms. Microarray analysis revealed 1,968 and 1,150 genes commonly regulated by DEX, FA, and TA in TM 86 and TM 93, respectively. These genes included RGC32, OCA2, ANGPTL7, MYOC, FKBP5, SAA1 and ZBTB16. In addition, each GC specifically regulated a unique set of genes in both TM cell lines. Using Ingenuity Pathway Analysis (IPA) software, analysis of the data from TM 86 cells showed that DEX significantly regulated transcripts associated with RNA post-transcriptional modifications, whereas FA and TA modulated genes involved in lipid metabolism and cell morphology, respectively. In TM 93 cells, DEX significantly regulated genes implicated in histone methylation, whereas FA and TA altered genes associated with cell cycle and cell adhesion, respectively.</p> <p>Conclusion</p> <p>Human trabecular meshwork cells in culture express all known GRα and GRβ translational isoforms, and GCs with similar potency but subtly different chemical structure are capable of regulating common and unique gene subsets and presumably biologic responses in these cells. These GC structure-dependent effects appear to be TM cell-lineage dependent.</p

Disparities in self-reported postpartum depression among Asian, Hawaiian, and Pacific Islander women in Hawai‘i: Pregnancy, Risk, Assessment, and Monitoring System (PRAMS), 2004-2007

Postpartum depression affects 10–20% of women and causes significant morbidity and mortality among mothers, children, families, and society, but little is known about postpartum depression among the individual Asian and Pacific Islander racial/ethnic groups. This study sought to identify the prevalence of postpartum depression among common Asian and Pacific Islander racial/ethnic groups. Data from the Hawaii Pregnancy Risk Assessment and Monitoring System (PRAMS), a population-based surveillance system on maternal behaviors and experiences before, during, and after the birth of a live infant, were analyzed from 2004 through 2007 and included 7,154 women. Questions on mood and interest in activities since giving birth were combined to create a measure of Self-reported Postpartum Depressive Symptoms (SRPDS). A series of generalized logit models with maternal race or ethnicity adjusted for other sociodemographic characteristics evaluated associations between SRPDS and an intermediate level of symptoms as possible indicators of possible SRPDS. Of all women in Hawaii with a recent live birth, 14.5% had SRPDS, and 30.1% had possible SRPDS. The following Asian and Pacific Islander racial or ethnic groups were studied and found to have higher odds of SRPDS compared with white women: Korean (adjusted odds ratio [AOR] = 2.8;95% confidence interval [CI]: 2.0–4.0), Filipino (AOR = 2.2;95% CI: 1.7–2.8), Chinese (AOR = 2.0;95% CI: 1.5–2.7), Samoan (AOR = 1.9;95% CI: 1.2–3.2), Japanese (AOR = 1.6;95% CI: 1.2–2.2), Hawaiian (AOR = 1.7;95% CI: 1.3–2.1), other Asian (AOR = 3.3;95% CI: 1.9–5.9), other Pacific Islander (AOR = 2.2;95% CI: 1.5–3.4), and Hispanic (AOR = 1.9;95% CI: 1.1–3.4). Women who had unintended pregnancies (AOR = 1.4;95% CI: 1.2–1.6), experienced intimate partner violence (AOR = 3.7;95% CI: 2.6–5.5), smoked (AOR = 1.5;95% CI: 1.2–2.0), used illicit drugs (AOR = 1.9;95% CI: 1.3–3.9), or received Women, Infant, and Children (WIC) benefits during pregnancy (AOR = 1.4;95% CI: 1.2–2.6) were more likely to have SRPDS. Several groups also were at increased risk for possible SRPDS, although this risk was not as prominent as seen with the risk for SRPDS. One in seven women reported SRPDS, and close to a third reported possible SRPDS. Messages about postpartum depression should be incorporated into current programs to improve screening, treatment, and prevention of SRPDS for women at risk

L-Ilf3 and L-NF90 Traffic to the Nucleolus Granular Component: Alternatively-Spliced Exon 3 Encodes a Nucleolar Localization Motif

Ilf3 and NF90, two proteins containing double-stranded RNA-binding domains, are generated by alternative splicing and involved in several functions. Their heterogeneity results from posttranscriptional and posttranslational modifications. Alternative splicing of exon 3, coding for a 13 aa N-terminal motif, generates for each protein a long and short isoforms. Subcellular fractionation and localization of recombinant proteins showed that this motif acts as a nucleolar localization signal. Deletion and substitution mutants identified four arginines, essential for nucleolar targeting, and three histidines to stabilize the proteins within the nucleolus. The short isoforms are never found in the nucleoli, whereas the long isoforms are present in the nucleoplasm and the nucleoli. For Ilf3, only the posttranslationally-unmodified long isoform is nucleolar, suggesting that this nucleolar targeting is abrogated by posttranslational modifications. Confocal microscopy and FRAP experiments have shown that the long Ilf3 isoform localizes to the granular component of the nucleolus, and that L-Ilf3 and L-NF90 exchange rapidly between nucleoli. The presence of this 13 aminoacid motif, combined with posttranslational modifications, is responsible for the differences in Ilf3 and NF90 isoforms subcellular localizations. The protein polymorphism of Ilf3/NF90 and the various subcellular localizations of their isoforms may partially explain the various functions previously reported for these proteins

Structure of a highly conserved domain of rock1 required for shroom-mediated regulation of cell morphology

Rho-associated coiled coil containing protein kinase (Rho-kinase or Rock) is a well-defined determinant of actin organization and dynamics in most animal cells characterized to date. One of the primary effectors of Rock is non-muscle myosin II. Activation of Rock results in increased contractility of myosin II and subsequent changes in actin architecture and cell morphology. The regulation of Rock is thought to occur via autoinhibition of the kinase domain via intramolecular interactions between the N-terminus and the C-terminus of the kinase. This autoinhibited state can be relieved via proteolytic cleavage, binding of lipids to a Pleckstrin Homology domain near the C-terminus, or binding of GTP-bound RhoA to the central coiled-coil region of Rock. Recent work has identified the Shroom family of proteins as an additional regulator of Rock either at the level of cellular distribution or catalytic activity or both. The Shroom-Rock complex is conserved in most animals and is essential for the formation of the neural tube, eye, and gut in vertebrates. To address the mechanism by which Shroom and Rock interact, we have solved the structure of the coiled-coil region of Rock that binds to Shroom proteins. Consistent with other observations, the Shroom binding domain is a parallel coiled-coil dimer. Using biochemical approaches, we have identified a large patch of residues that contribute to Shrm binding. Their orientation suggests that there may be two independent Shrm binding sites on opposing faces of the coiled-coil region of Rock. Finally, we show that the binding surface is essential for Rock colocalization with Shroom and for Shroom-mediated changes in cell morphology. © 2013 Mohan et al