Effects of COX inhibition on blood pressure and kidney function in ACE inhibitor-treated blacks and hispanics. (49/3143)

Cyclo-oxygenase (COX) inhibitors attenuate the antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors and reduce kidney function. The study tests the hypothesis that these two classes of drugs have similar effects on glomerular filtration rate (GFR) and 24-hour blood pressure. The primary endpoint was change in 24-hour systolic blood pressure. Using a randomized crossover design, 25 black and Hispanic hypertensive participants (mean age 58+/-3 years) with osteoarthritis were studied. All participants received an ACE inhibitor at baseline. Once systolic blood pressure was <140 mm Hg, either celecoxib 200 mg/d or diclofenac 75 mg twice daily for 4 weeks was started. After measurements were obtained, all participants underwent a 2-week washout period and crossed over to the other drug for 4 weeks. A significant difference in mean 24-hour systolic blood pressure was noted between groups at 4 weeks (+4.1+/-1.1 mm Hg diclofenac versus +0.6+/-0.6 mm Hg celecoxib; P=0.01). However, because celecoxib has duration of action shorter than 24 hours, we compared ambulatory values at celecoxib trough and peak activities. At peak, no difference in systolic blood pressure was noted between agents (+3.6+/-0.04 mm Hg diclofenac versus +4.2+/-1.9 mm Hg celecoxib; P=0.67). GFR was also differentially affected at 24 hours (-9.9+/-2.4 mL/min diclofenac versus -0.4+/-1.2 mL/min celecoxib; P=0.01). We conclude that diclofenac and celecoxib increase systolic blood pressure at peak levels; however, these agents differ in their 24-hour effects. Differences observed in blood pressure response between COX inhibitors may not be related in their sensitivity but rather their dosing frequency.  (+info)

The role of carbon monoxide in the gastrointestinal tract. (50/3143)

Carbon monoxide (CO) is a biologically active product of haem metabolism that contributes to the normal physiology of the gastrointestinal tract. In this article, we review recent data showing that CO is an integral regulator of gastrointestinal motility and an important factor in the response to gastrointestinal injury. CO is generated by haem oxygenase-2 (HO-2), which is constitutively expressed in many inhibitory neurones of the vertebrate enteric nervous system. The membrane potential gradients along and across the muscle layers of the gastrointestinal tract require the generation of CO by haem oxygenase-2. The presence of CO is also necessary for normal inhibitory neurotransmission in circular smooth muscle and appears to permit nitric oxide-mediated inhibitory neurotransmission. Genetic deletion of the haem oxygenase-2 gene in mice slows gut transit. The other major CO synthetic enzyme, haem oxygenase-1 (HO-1) is induced under conditions of stress or injury. Recent studies have demonstrated that up-regulation of haem oxygenase-1 protects the gut from several types of gastrointestinal injury, suggesting that CO or induction of HO-1 may find therapeutic use in gastrointestinal diseases and injuries. Furthermore, it is anticipated that the understanding of CO-mediated signalling in the gastrointestinal tract will inform studies in other tissues that express haem oxygenases.  (+info)

Review article: clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics. (51/3143)

Antidopaminergic gastrointestinal prokinetics (bromopride, clebopride, domperidone, levosulpiride and metoclopramide) have been exploited clinically for the management of motor disorders of the upper gastrointestinal tract, including functional dyspepsia, gastric stasis of various origins and emesis. The prokinetic effect of these drugs is mediated through the blockade of enteric (neuronal and muscular) inhibitory D2 receptors. The pharmacological profiles of the marketed compounds differ in terms of their molecular structure, affinity at D2 receptors, ability to interact with other receptor systems [5-hydroxytryptamine-3 (5-HT3) and 5-HT4 receptors for metoclopramide; 5-HT4 receptors for levosulpiride) and ability to permeate the blood-brain barrier (compared with the other compounds, domperidone does not easily cross the barrier). It has been suggested that the serotonergic (5-HT4) component of some antidopaminergic prokinetics may enhance their therapeutic efficacy in gastrointestinal disorders, such as functional dyspepsia and diabetic gastroparesis. The antagonism of central D2 receptors may lead to both therapeutic (e.g. anti-emetic effect due to D2 receptor blockade in the area postrema) and adverse (including hyperprolactinaemia and extrapyramidal dystonic reactions) effects. As the pituitary (as well as the area postrema) is outside the blood-brain barrier, hyperprolactinaemia is a side-effect occurring with all antidopaminergic prokinetics, although to different extents. Extrapyramidal reactions are most commonly observed with compounds crossing the blood-brain barrier, although with some differences amongst the various agents. Prokinetics with a high dissociation constant compared with that of dopamine at the D2 receptor (i.e. compounds that bind loosely to D2 receptors in the nigrostriatal pathway) elicit fewer extrapyramidal signs and symptoms. A knowledge of central and peripheral D2 receptor pharmacology can help the clinician to choose between the antidopaminergic prokinetics to obtain a more favourable risk/benefit ratio.  (+info)

Characterization of in vitro gutlike organ formed from mouse embryonic stem cells. (52/3143)

Using an embryoid body (EB) culture system, we have made a functional organlike cluster: the "gut" from embryonic stem (ES) cells (ES gut). There are many types of ES clusters, because ES cells have a pluripotent ability to develop into a wide range of cell types. Before inducing specific differentiation by exogenously added factors, we characterized comprehensive physiological and morphological properties of ES guts. Each ES gut has a hemispherical (or cystic) structure and exhibits spontaneous contractions [mean frequency: 13.5 +/- 8.8 cycles per min (cpm)]. A dense distribution of interstitial cells of Cajal (ICC) was identified by c-Kit immunoreactivity, and specific subcellular structures of ICC and smooth muscle cells were identified with electron microscopy. ICC frequently formed close contacts with the neighboring smooth muscle cells and occasionally formed gap junctions with other ICC. Widely propagating intracellular Ca(2+) concentration oscillations were generated in the ES gut from the aggregates of c-Kit immunopositive cells. Plateau potentials, possibly pacemaker potentials in ICC, and electrical slow waves were recorded for the first time. These events were nifedipine insensitive, as in the mouse gut. Our present results indicate that the rhythmic pacemaker activity generated in ICC efficiently spreads to smooth muscle cells and drives spontaneous rhythmic contractions of the ES gut. The present characterization of physiological and morphological properties of ES gut paves the way for making appropriate models to investigate the origin of rhythmicity in the gut.  (+info)

Effects of ageing on gastrointestinal motor function. (53/3143)

BACKGROUND: Existing data on the effect of ageing on gastrointestinal motility are few. In this study, we assessed the propulsive effect of all main segments of the gastrointestinal tract in a group of healthy older people. METHODS: 16 healthy volunteers (eight women, eight men) of mean age 81 years (range 74-85 years) participated in the study. Gastric emptying and small intestinal and colonic transit rates were determined by gamma camera technique. The technique was also used to measure the postprandial frequency of antral contractions. Furthermore, we assessed the effects of gender, body mass index and smoking on the motility variables. The results were compared with data from 16 healthy individuals (eight women, eight men) of mean age 24 years (range 20-30 years). RESULTS: Advanced age did not influence gastric emptying or small intestinal transit rate. Older individuals had a slower colonic transit than young individuals (P = 0.0008). No difference was found in postprandial frequency of antral contractions between older and young subjects. None of the motility variables was affected by gender or body mass index. Smokers had a faster colonic transit than non-smokers (P = 0.0022). CONCLUSION: Normal ageing seems to reduce the propulsive capacity of the colon, whereas gastric and small intestinal motility is not affected.  (+info)

Multiresistant coagulase-negative staphylococci disseminate frequently between intubated patients in a multidisciplinary intensive care unit. (54/3143)

INTRODUCTION: The intensive care unit is burdened with a high frequency of nosocomial infections often caused by multiresistant nosocomial pathogens. Coagulase-negative staphylococci (CoNS) are reported to be the third causative agent of nosocomial infections and the most frequent cause of nosocomial bloodstream infections. CoNS are a part of the normal microflora of skin but can also colonize the nasal mucosa, the lower airways and invasive devices. The main aim of the present study was to investigate colonization and the rate of cross-transmissions of CoNS between intubated patients in a multidisciplinary intensive care unit. MATERIALS AND METHODS: Twenty consecutive patients, ventilated for at least 3 days, were included. Samples were collected from the upper and lower airways. All samples were cultured quantitatively and CoNS were identified by morphology and biochemical tests. A total of 199 CoNS isolates from 17 patients were genetically fingerprinted by pulsed-field gel electrophoresis in order to identify clones and to monitor dissemination within and between patients. RESULTS: An unexpected high number of transmission events were detected. Five genotypes were each isolated from two or more patients, and 14/20 patients were involved in at least one and up to eight probable transmission events. CONCLUSIONS: A frequent transmission of CoNS was found between patients in the intensive care unit. Although transmission of bacteria does not necessarily lead to infection, it is nevertheless an indication that infection control measures can be improved.  (+info)

Stimulation by cadmium of myohemerythrin-like cells in the gut of the annelid Nereis diversicolor. (55/3143)

Isolated guts of Nereis diversicolor revealed the existence of a cadmium-binding protein, the MPII, belonging to the group of hemerythrins and myohemerythrins. The presence of MPII in the cells of the intestine was demonstrated by immunocytochemistry, using anti-MPII, a monoclonal antibody. In addition, using in situ hybridization and northern blotting, it was shown that MPII-cells are the site of synthesis of this molecule. Exposure of the worms to cadmium led to the cellular activation process of MPII-cells (i.e. transformation of the nucleolus, development of the endoplasmic reticulum and the Golgi apparatus), although MPII mRNA transcript levels were unchanged. Enzyme-linked immunosorbent assay (ELISA) of gut extracts revealed that MPII levels were increased after exposure to Cd, so it appears that this protein is synthesized as a response to Cd exposure without any new synthesis of mRNA. This mechanism of regulation is quite similar to that reported in the case of mammalian ferritin and may be involved in the regulation of Cd levels in this worm.  (+info)

Evaluation of in vivo genotoxicity of cypermethrin in Drosophila melanogaster using the alkaline Comet assay. (56/3143)

The single cell gel electrophoresis (SCGE) assay, also known as the Comet assay, is one of the most promising genotoxicity tests developed in recent years to measure and analyse DNA damage in single cells. The present study was undertaken to assess the in vivo genotoxicity of the synthetic pyrethroid cypermethrin in brain ganglia and anterior mid gut of Drosophila melanogaster. Freshly emerged first instar larvae (22 +/- 2 h) were placed in different concentrations of cypermethrin (0.0004, 0.0008, 0.002, 0.2 and 0.5 p.p.m.) mixed in standard Drosophila food and allowed to grow. At 96 +/- 2 h, brain ganglia and anterior midgut from control and treated larvae were dissected out, single cell suspensions were prepared and a Comet assay was performed. Our results revealed a significant dose-dependent increase in DNA damage in the cells of brain ganglia and anterior midgut of D.melanogaster exposed to cypermethrin as compared with controls (P < 0.05 at 0.002 p.p.m.; P < 0.001 at 0.2 and 0.5 p.p.m.). The present study shows in vivo genotoxicity of cypermethrin even at very low concentrations, which proves D.melanogaster as a model for in vivo genotoxicity assessment using the Comet assay.  (+info)