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Inhibitor Administration (inhibitor + administration)
Selected AbstractsPredictors for squamous re-epithelialization of Barrett's esophagus after endoscopic biopsyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2007Yuji Amano Abstract Background and Aim:, Acid suppressive therapy has been reported to regress Barrett's esophagus. However, it is still controversial as to whether all Barrett's esophagus patients respond to this therapy. The factors that might facilitate newly developed squamous re-epithelialization after biopsy excision of Barrett's mucosa were evaluated to identity individuals who may favorably respond to the regression therapy. Methods:, Two hundred and forty-seven biopsy sites from 185 patients with Barrett's esophagus were examined by endoscopy to investigate possible squamous re-epithelialization of Barrett's mucosa after endoscopic biopsy. Before endoscopic examination, all participants were requested to answer questionnaires concerning sociodemographic characteristics, lifestyle habits and drugs usage. The mucin phenotype, Cdx2 expression, cyclooxygenase-2 expression, cellular proliferation and apoptosis of Barrett's mucosa were immunohistochemically investigated in the biopsy samples taken from Barrett's esophagus. The influence of these factors on the newly developed squamous re-epithelialization of Barrett's mucosa after endoscopic biopsy excision was evaluated. Results:, By multivariate analysis, the independent factors that favored squamous re-epithelialization were the gastric mucin predominant phenotype of Barrett's mucosa and the absence of Cdx2 protein expression. In Barrett's mucosa with the gastric predominant mucin phenotype, proton pump inhibitor administration, the absence of reflux esophagitis and a low proliferating cell nuclear antigen index were found to be independent predictors for squamous re-epithelialization. Conclusions:, The absence of the intestinal predominant mucin phenotype was a positive predictor for newly developed squamous re-epithelialization at the site of biopsy of Barrett's mucosa. Only Barrett's esophagus with the gastric predominant mucin phenotype may predict a favorable response to acid suppressive therapy. [source] Chronic exposure to nicotine and saquinavir decreases endothelial Notch-4 expression and disrupts blood-brain barrier integrityJOURNAL OF NEUROCHEMISTRY, Issue 2 2010Vamshi K. Manda J. Neurochem. (2010) 115, 515,525. Abstract Since the advent of HAART, there have been substantial improvements in HIV patient survival; however, the prevalence of HIV associated dementia has increased. Importantly, HIV positive individuals who smoke progress to HIV associated neurological conditions faster than those who do not. Recent in vitro data have shown that pharmacological levels of saquinavir causes endothelial oxidative stress and significantly decreases Notch-4 expression, a primary protein involved in maintaining stability of blood-brain barrier (BBB) endothelium. This is concerning as nicotine can also generate reactive oxygen species in endothelium. It is largely unknown if pharmacological doses of these drugs can cause a similar in vivo down-regulation of Notch-4 and if there is a concurrent destabilization of the integrity of the BBB. The data herein show: (i) nicotine and protease inhibitors cause an additive oxidative stress burden in endothelium; (ii) that the integrity of the BBB is disrupted after concurrent chronic nicotine and protease inhibitor administration; and (iii) that BBB endothelial dysfunction is correlated with a decrease in Notch-4 and ZO-1 expression. Considering the high prevalence of smoking in the HIV infected population (3- to 4-fold higher than in the general population) this data must be followed up to determine if all protease inhibitors cause a similar BBB disruption or if there is a safer alternative. In addition, this data may suggest that the induced BBB disruption may allow foreign molecules to gain access to brain and be a contributing factor to the slow progression of HIV associated dementia. [source] The Effect of Angiotensin-Converting Enzyme Inhibitors of Left Atrial Pressure in Dogs with Mitral Valve RegurgitationJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2010T. Ishikawa Background: Despite many epidemiological reports concerning the efficacy of angiotensin-converting enzyme (ACE) inhibitors in dogs with mitral regurgitation (MR), the hemodynamic effects of ACE inhibitor administration have not been fully evaluated. Objectives: To document left atrial pressure (LAP) in dogs with MR administered ACE inhibitors, in order to obtain interesting information about daily LAP changes with administration of ACE inhibitors. Animals: Five healthy Beagle dogs weighing 9.8 to 14.2 kg (2 males and 3 females; aged 2 years). Methods: Experimental, crossover, and interventional study. Chordae tendineae rupture was induced, and a radiotelemetry transmitter catheter was inserted into the left atrium. LAP was recorded for 72 consecutive hours during which each of 3 ACE inhibitors,enalapril (0.5 mg/kg/d), temocapril (0.1 mg/kg/d), and alacepril (3.0 mg/kg/d),were administered in a crossover study. Results: Averaged diurnal LAP was significantly, but slightly reduced by alacepril (P= .03, 19.03 ± 3.01,18.24 ± 3.07 mmHg). The nightly drops in LAP caused by alacepril and enalapril were significantly higher than the daily drops (P= .03, ,0.98 ± 0.19 to ,0.07 ± 0.25 mmHg, and P= .03, ,0.54 ± 0.21,0.02 ± 0.17 mmHg, respectively), despite the fact that the oral administrations were given in the morning. Systolic blood pressure (122.7 ± 14.4,117.4 ± 13.1 mmHg, P= .04) and systemic vascular resistance (5800 ± 2685,5144 ± 2077 dyne × s/cm5, P= .03) were decreased by ACE inhibitors. Conclusions and Clinical Importance: ACE inhibitors decrease LAP minimally, despite reductions in left ventricular afterload. ACE inhibitors should not be used to decrease LAP. [source] Relationship between post-traumatic stress disorder-like behavior and reduction of hippocampal 5-bromo-2,-deoxyuridine-positive cells after inescapable shock in ratsPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 6 2008Akihito Kikuchi md Aim:, Inescapable shocks (IS) have been reported to reduce the number of 5-bromo-2,-deoxyuridine (BrdU)-positive cells in hippocampus. Antidepressants prevent this reduction, and the role of neurogenesis in depression is now suggested. It has been reported, however, that the number of BrdU-positive cells was not different between the rats that developed learned helplessness and those that did not. This suggests that reduction of neurogenesis does not constitute a primary etiology of depression. It has been previously shown that IS can cause various post-traumatic stress disorder (PTSD)-like behavioral changes in rats. The aim of the present was therefore to examined whether the reduction of BrdU-positive cells relates to any PTSD-like behavioral changes in this paradigm. Methods:, Rats were given either inescapable foot-shocks (IS) or not shocked (non-S) treatment in a shuttle box on day 1 and received BrdU injections once daily during the first week after IS/non-S treatment. On day 14, rats treated with IS and non-S were given an avoidance/escape test in the shuttle box and dorsal hippocampal SGZ were analyzed by BrdU immunohistochemistry. Results:, In accordance with previously reported results, IS loading resulted in fewer BrdU-positive cells in the hippocampal subgranular zone (SGZ). Furthermore, in the IS-treated group, the number of BrdU-positive cells in the hippocampal SGZ was negatively correlated at a significant level with several hyperactive behavioral parameters but not with hypoactive behavioral parameters. Earlier findings had indicated that chronic selective serotonin re-uptake inhibitor administration, which is known to increase hippocampal neurogenesis, restored the increase in hypervigilant/hyperarousal behavior but did not attenuate the increase in numbing/avoidance behavior. Conclusion:, The regulatory mechanism responsible for the decreased proliferation and survival of cells in the hippocampus may be related to the pathogenic processes of hypervigilance/hyperarousal behaviors. [source] Feasibility of the Use of Phosphodiesterase Type 5 Inhibitors in a Pharmacologic Prevention Program for Recurrent PriapismTHE JOURNAL OF SEXUAL MEDICINE, Issue 6 2006Arthur L. Burnett MD ABSTRACT Introduction., Recurrent ischemic priapism is an enigmatic erectile disorder in need of improved clinical interventions to avert its known, potentially serious complications. Aim., To evaluate the use of a long-term, continuous phosphodiesterase type 5 (PDE5) inhibitor therapeutic regimen in controlling recurrent ischemic priapism and its feasibility in a clinical management program for the disorder. Main Outcome Measures., The main outcome measure was reduction in frequency or duration of priapism episodes. A secondary outcome measure was preservation of erectile ability. Methods., We retrospectively evaluated the clinical progress of seven patients (age 22,37 years) with sickle cell disease-associated "stuttering" priapism (N = 4) and idiopathic recurrent priapism (N = 3), who were counseled and consented to the "off-label" use of the PDE5 inhibitors sildenafil citrate and tadalafil. The medications were administered according to a specified therapeutic regimen based on scientific evidence that chronic PDE5 inhibitor administration in priapism contexts effectively reconditions PDE5 regulatory function in the penis. The duration of clinical follow-up extended through 2 years. Results., All seven patients were confirmed to have recurrent ischemic priapism without identifiable pharmacologic, traumatic, or neoplastic disease associations based on clinical history, physical examination, laboratory testing, and penile diagnostics. PDE5 inhibitor treatment was successful in alleviating or resolving priapism recurrences in six of the seven patients. Erectile function was unchanged in six patients and improved in one patient at last follow-up compared with baseline status. All the patients reported that PDE5 inhibitor therapy was well tolerated and did not cause any adverse effects limiting their continued use of the medication. Conclusions., Because of their efficacy, safety, and tolerability as shown in this case series, PDE5 inhibitors would appear to have a possible role in a rigorously implemented clinical management program to control recurrent priapism. However, completion of a controlled clinical trial is necessary to confirm the utility of this treatment. Burnett AL, Bivalacqua TJ, Champion HC, and Musicki B. Feasibility of the use of phosphodiesterase type 5 inhibitors in a pharmacologic prevention program for recurrent priapism. J Sex Med 2006;3:1077,1084. [source] | ||||||||||