Influence of low temperature on bronchodilatation induced by terbutaline administered by metered dose or dry powder inhalers in asthmatics.

Low temperatures may affect dose delivery efficacy and clinical effectiveness of medication aerosols. In this study we examine the effect of cold ambient temperature on the bronchodilatation produced by terbutaline delivered from a chlorofluorocarbon pressurized metered dose inhaler (pMDI) compared to a multi-dose dry powder inhaler (DPI). Fourteen stable asthmatics were studied on two consecutive days. On day 1, after measuring FEV1 at room temperature (22 degrees C), each patient was randomized to receive 500 microg of terbutaline delivered from pMDI or DPI stored for 24 h at 22 degrees C with FEV1 recorded 20 min post-dose; then, patients were placed in a chamber at -10 degrees C, and af…

Olive Oil–Based Lipid Emulsion's Neutral Effects on Neutrophil Functions and Leukocyte–Endothelial Cell Interactions

Infection remains a drawback of parenteral nutrition (PN), probably related, among other factors, to immunosuppressive effects of its lipid component. Newer preparations may have lesser immunosuppressive impact. This study examines the effects of an olive oil-based lipid emulsion (long-chain triacylglycerols-monounsaturated fatty acids [LCT-MUFA]; ClinOleic) on various functions of human neutrophils in vitro and on rat leukocyte-endothelial cell interactions in vivo compared with LCT (Intralipid) and 50% LCT-50% medium-chain triacylglycerols (MCT; Lipofundin) mixture.Neutrophils isolated from healthy donors were incubated with concentrations (0.03-3 mmol/L) of lipid emulsions encompassing c…

EFFECT OF CLONIDINE ON ACUTE AND CHRONIC GASTRIC ULCER

EFFECT OF DRUGS ON THE CIRCULAR MUSCULATURE OF THE ISOLATED MOUSE LOWER ESOPHAGUS

Effects of cimetidine, atropine and prostaglandin E2 on rat mucosal erosions produced by intragastric distension

Abstract The effects of three typical antisecretory agents: cimetidine, atrophine and prostaglandin E2 were compared on an acute rat gastric ulcer model which consisted of perfusing the stomach continuously, at a high intraluminal pressure (120 mm H2O), with a simulated gastric juice (0.1 M HCl plus 600 mg pepsin/1). As the acid and pepsin are given exogenously the inhibitory action of the antisecretory drugs is obviated in this model. Cimetidine and atropine failed to reduce gastric erosions, whereas prostaglandin E2 markedly reduced the severity of the mucosal lesions with respect to control values. Long-term treatment with cimetidine also failed to increase the resistance of the gastric …

THE EFFECT OF CLONIDINE ON ACID SECRETION STIMULATED BY HISTAMINE AND PENTAGRASTRIN IN THE ISOLATED MOUSE STOMACH

CLONIDINE, A PARTIAL AGONIST OF THE HISTAMINERGIC H2 RECEPTORS?

Changes inα-tocopherol and retinol levels during cardiopulmonary bypass correlate with maximal arterial partial pressure of oxygen

Cardiopulmonary bypass (CPB) is associated with oxidative stress. This study examined antioxidant levels in adults undergoing CPB surgery and their correlation with clinical variables. Arterial blood samples were obtained from 27 patients undergoing CPB. The time-course variation of vitamin C (spectrofluorimetry), alpha-tocopherol and retinol (HPLC) levels were determined. Plasma vitamin C rose initially but gradually decayed during reperfusion until 60% reduction of baseline values post-surgery. alpha-Tocopherol and retinol were reduced along CPB with post-operative values approximately 25% lower than baseline. No significant changes were found for selenium and glutathione peroxidase. PaO(…

Anti-inflammatory and anti-fibrotic profile of fish oil emulsions used in parenteral nutrition-associated liver disease.

Home parenteral nutrition (PN) is associated with many complications including severe hepatobiliary dysfunction. Commercial ω-6 fatty acid-soybean based-lipid emulsions in PN may mediate long term PN associate liver disease (PNALD) whereas ω-3-fish oil parenteral emulsions have shown to reverse PNALD in children. However, its clinical effectiveness in adults has been scarcely reported. In this work, we study the role of soybean and fish oil lipid commercial emulsions on inflammatory and profibrotic liver markers in adults with long term PNALD and in in vitro cellular models. Inflammatory and profibrotic markers were measured in serum of ten adults with long term PNALD and in culture superna…

Evaluation of the Ocular Tolerance of Three Tacrolimus Topical Pharmaceutical Preparations by Bovine Corneal Opacity and Permeability Test.

Tacrolimus ocular preparations are commonly employed in autoimmune or inflammatory ocular disorders. However, currently there are not yet approved ocular formulations. Tacrolimus ocular side effects have been reported in clinical use, so the evaluation of different pharmaceutical preparations is mandatory. In this study, the local corneal tolerance and safety profile of three common tacrolimus 0.03% pharmaceutical preparations were evaluated.Corneal irritation and permeability of tacrolimus preparations were evaluated with the bovine corneal opacity and permeability (BCOP) test. Complementary corneal hematoxylin/eosin and immunohistochemistry staining for tight junctions and adherent juncti…

Effects of calcium channel blockers on gastric emptying and acid secretion of the rat in vivo.

Abstract Experiments were designed to evaluate the effects of three calcium channel blockers (verapamil, diltiazem and cinnarizine) on gastric emptying and secretion in the rat. Pretreatment with the calcium blockers delayed gastric emptying of phenol red in a dose-dependent manner. Verapamil was the most effective of the agents tested. Verapamil and diltiazem inhibited gastric acid secretion in the pylorus-ligated rat without affecting pepsin output. Cinnarizine was ineffective in this model. When the perfused lumen of the anaesthetized rat was used, verapamil was found to inhibit responses to carbachol or histamine more than those to pentagastrin. Further, we found a greater sensitivity t…

Alteration of vancomycin pharmacokinetics during cardiopulmonary bypass in patients undergoing cardiac surgery.

The alteration of vancomycin pharmacokinetics during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery was studied. Eighteen patients were enrolled in the study. Vancomycin (1 g) was intravenously infused one to two hours before surgery. Blood samples were taken before, during, and after CPB. Serum drug concentrations were determined by an automated fluorescence polarization immunoassay and adjusted, with a bayesian analysis, to a bi-compartmental model implemented in a pharmacokinetic system program. Serum creatinine, hematocrit, and plasma proteins were also measured before, during, and after CPB. During CPB, serum creatinine, hematocrit, and plasma protein values all de…

EFFECT OF A β2 ADRENOCEPTOR AGONIST ON ACUTE AND CHRONIC GASTRIC ULCER IN THE RAT

Osimertinib in first-line treatment of advanced EGFR-mutated non-small-cell lung cancer: a cost–effectiveness analysis

Aim: Osimertinib improves progression-free survival in first-line EGFR mutation–positive non-small-cell lung cancer. Materials & methods: A Markov cohort model including costs, utilities and disutilities, was conducted to estimate quality-adjusted life-year (QALY) and incremental cost–effectiveness ratio when treating with osimertinib versus standard first-line tyrosine kinase inhibitors (TKIs). Results: Osimertinib presented higher QALYs (0.61) compared with standard EGFR–TKIs (0.42). Osimertinib costs were €83,258.99, in comparison with €29,209.45 for the standard EGFR–TKIs. An incremental cost–effectiveness ratio of €273,895.36/QALY was obtained for osimertinib. Conclusion: Osimerti…

MECHANISM OF INHIBITION OF GASTRIC ACID SECRETION BY HYPERTONIC SOLUTIONS

Effects of beta-adrenoceptor drug stimulation on various models of gastric ulcer in rats.

Abstract 1. Experiments were designed to evaluate the effect of the pharmacological activation of beta-adrenoceptors on various models of gastric ulcer in the rat. 2. Pretreatment with the beta-adrenoceptor stimulant drugs, isoprenaline or salbutamol, significantly inhibited stress-induced gastric ulcers. This anti-ulcer effect was abolished by propranolol but not by atenolol, suggesting that beta 2-adrenoceptors mediate this response. 3. In the pylorus-ligation model, salbutamol inhibited lesion formation and reduced the intragastric content of hydrogen ions, histamine and pepsin although the latter was only affected with the higher dose of salbutamol. 4. Salbutamol also prevented the ulce…