Cyclic AMP formation in chicken brain: effect of vasoactive intestinal peptide, peptide histidine-isoleucine (PHI), and some PHI-related peptides

Vasoactive intestinal peptide (chicken form; chVIP), peptide histidine-isoleucine (porcine and rat forms; pPHI and rPHI), D-Phe(4) derivative of porcine PHI (D-Phe(4)-pPHI), peptide histidine-methionine (PHM; human PHI), and helodermin, were tested for their ability to stimulate cAMP production in [(3)H]adenine-prelabeled slices of chick cerebral cortex (CCx) and hypothalamus (HTh). The chVIP (0.1-3 microM) concentration-dependently and potently stimulated cAMP production in HTh and CCx; the responses observed after 3 microM of chVIP were comparable to those produced by 0.1 microM PACAP38. Helodermin (5 microM) moderately but significantly stimulated cAMP formation in both HTh and CCx, whereas pPHI, rPHI, PHM at 5 microM concentration only weakly affected cAMP production in CCx, and were inactive in HTh; D-Phe(4)-pPHI was inactive in both tissues. These data demonstrate that chVIP, PACAP, and to a lesser extent helodermin were capable of potently stimulating cAMP generation in the avian central nervous system. PHI-related peptides showed only weak or no activity, depending on the tissue.     

Kinetics of hydrolysis of diltiazem hydrochloride in aqueous solutions

The kinetics of hydrolysis of diltiazem hydrochloride in aqueous solutions at 313, 323, 333 and 353 K over the pH-range 0.4-9.7 has been investigated. The decomposition was followed by the HPLC method. The pH-rate profile was accounted for by the specific acid- and base-catalysed reactions and also by assuming spontaneous or water-catalysed decomposition of both dissociated and undissociated molecules of diltiazem. Various buffer substances were found to exhibit general acid and base catalysis of the degradation. Thermodynamic parameters of the reaction: energy and enthalpy of activation and the frequency factor for the specific rate constants were determined.     

Kinetics of diltiazem hydrochloride in solid phase

The influence of temperature (353, 358, 363, 368, and 373 K) and relative humidity (76.4, 66.5, 60.5 and 50.9% RH) on the stability of diltiazem hydrochloride in the solid phase was investigated. The decomposition was followed by a HPLC method with UV detection. The kinetic (rate constants, t0.1 and t0.5) and thermodynamic parameters (energy, entalpy and entropy of activation) of the degradation of diltiazem hydrochloride were calculated.     

The cellular composition and macrophage phenotype in induced sputum in smokers and ex-smokers with COPD

STUDY OBJECTIVES: The relationship between smoking and COPD has been well-documented. We investigated the impact of cigarette smoking on airway inflammation in COPD patients. DESIGN: Changes in cell profiles in induced sputum (IS) samples from smokers with COPD and patients who ceased smoking were compared. SETTING: Department of pneumonology in a university hospital. PATIENTS: IS samples were collected from 17 smokers and 17 ex-smokers with COPD. INTERVENTIONS: We examined IS samples for differential cell counts and macrophage phenotypes determined by immunocytochemistry with monoclonal antibodies anti-CD11b, anti-CD14, anti-CD54, and anti-CD71. MEASUREMENTS AND RESULTS: The median IS volume was greater and the total cell count was higher in smokers than in ex-smokers. The difference, however, was not significant. We did not find any significant differences in the proportions of cells and in the phenotypes of macrophages between the two groups, with the proportion of eosinophils being slightly higher in the group of smokers. We found, however, a significant positive correlation between the decrease in pulmonary function parameters and the number of pack-years smoked, an inverse correlation of pulmonary function test results with the number of lymphocytes in IS, and a correlation between some changes in the expression of macrophage surface markers and smoking history. There was no correlation between the time from smoking cessation and any cellular component found in IS samples. CONCLUSIONS: The analysis of IS samples in patients with COPD revealed no significant differences in cell count and macrophage phenotypes between active smokers and ex-smokers.     

Influence of salbutamol on the anticonvulsant potency of the antiepileptic drugs in the maximal electroshock-induced seizures in mice

Backgroundβ₂-Adrenergic receptor agonists are widely used agents in the treatment of asthma or preterm labor. Since prevalence of asthma was shown to be higher in patients with epilepsy and modulation of noradrenergic system activity may modify epilepsy course, the aim of the present study was to examine the effect of salbutamol (SALB), one of the most commonly used β₂-adrenergic receptor agonist on the anticonvulsant potency of four classical antiepileptic drugs (AEDs): valproate (VPA), carbamazepine (CBZ), phenytoin (DPH) and phenobarbital (PB) in mice subjected to the maximal electroshock (MES)-induced seizures.MethodsSeizures were caused by a current delivered through ear-clip electrodes. The influence of AEDs and SALB on animals’ motor coordination and memory processes was also evaluated.ResultsSingle SALB injection did not change, whereas 7 days SALB administration decreased seizure threshold in the MES-induced seizures in mice. Moreover, SALB injected ip for 1 day and for 7 days lowered the antiepileptic activity of PB in the MES-induced seizures in mice, but did not change the effect of other analyzed AEDs: VPA, CBZ or DPH. Butoxamine, a selective β₂-adrenergic receptor antagonist, reversed SALB influence on the activity of PB. SALB given alone or in combination with the tested AEDs did not affect animals’ motor performance and memory after both single and 7 days administration.ConclusionsPresented results show that SALB may decrease the antiepileptic efficacy of PB. A special caution is advised to patients with epilepsy receiving β₂-adrenergic receptors agonists in the pharmacotherapy of pulmonary and obstetrical disorders.     

TGF-β1 gene polymorphisms and primary vesicoureteral reflux in childhood

The aim of this study was to assess the association between the transforming growth factor-β1 (TGF-β1) gene polymorphisms rs1800469 (commonly known as T-509C) and rs1982073 (commonly known as Leu ¹⁰→Pro) and primary vesicoureteral reflux (VUR) and renal scarring. Using a case–control approach, we examined 121 children with primary VUR and 169 controls. Genotyping of the TGF-β1 gene polymorphisms was performed by restriction fragment length polymorphism (RFLP) analysis. The ^99mTc-DMSA– or ^99mTc-unitiol–single photon emission computed tomography method was used to evaluate renal scars in 84 of 121 VUR children. Statistical analysis revealed differences in rs1800469 genotype frequencies between VUR patients and controls (p = 0.0021). Our data demonstrate that individuals homozygous for the TT genotype are at risk of primary VUR [odds ratio (95% confidence interval) = 2.7 (1.46–5.08)]. Distribution of the rs1982073 polymorphism was similar in VUR children and controls. In terms of renal scarring, patients were stratified into non-scar and scar subgroups, and no differences in the genotype frequencies of either polymorphism was found. Previous reports have shown that the TT genotype of the rs1800469 polymorphism is a risk factor for renal scarring in primary VUR, and the results of our study suggest that this same polymorphism is associated with susceptibility to this congenital uropathy.     

Application of Screening Methods,Shape Signatures and Engineered Biosensors in Early Drug Discovery Process

Purpose  

In this study, two unreported estrogen antagonists were identified using a combination of computational screening and a simple bacterial estrogen sensor.