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.     

Effects of doxycycline on the development of bone damage caused by prednisolone in rats

The aim of the present study was to investigate the effects of doxycycline on the development of bone damage caused by prednisolone in rats. The experiments were carried out on male WAG rats (200-260 g), divided into 2 control and 6 experimental groups receiving prednisolone (5 mg/kg im daily) or/and doxycycline (100 mg/kg po daily) for 2 or 4 weeks. The animals were sacrificed on the 15th or 29th day of the experiment and the following characteristics were examined: mass, length, mechanical properties, mineral and calcium content in the tibia and femur, width of endosteal and periosteal osteoid, endosteal and periosteal transverse growth, transverse cross-section area of the diaphysis and of the marrow cavity in the tibia, width of epiphyseal cartilage and width of trabeculae in the femur. Prednisolone caused features of osteopenia (inhibition of bone formation and intensification of bone resorption), which were stronger after 4 weeks of the experiment. Doxycycline administered alone for 2 or 4 weeks intensified the processes of bone formation and resorption. Doxycycline to some degree attenuated the influence of prednisolone on rat bones.     

Effects of alpha-escin on histomorphometrical parameters of long bones in rats with experimental post-steroid osteopenia

The excess of glucocorticosteroids leads to the development of osteopenia. A decreased bone formation rate and an increased bone resorption rate are observed. The aim of the present study was to investigate the effects of alpha-escin on the experimental prednisolone-induced osteopenia. The experiments were carried out on male Wistar rats with initial body weight of 240-310 g, divided into 4 groups (n = 6): Control, Alpha-escin, Prednisolone, Prednisolone + alpha-escin. Prednisolone (5 mg/kg im daily) and/or alpha-escin (100 mg/kg po daily) were administered for 28 days. Transverse cross-section surfaces of the cortical diaphysis and of the marrow cavity in the tibia, transverse growth, width of endosteal and periosteal osteoid, thickness of trabeculae and width of epiphyseal cartilage were examined. Prednisolone administration caused osteopenic changes in rat bones. Alpha-escin administered to the control rats did not exert statistically significant influence on the investigated bone parameters. Alpha-escin administration to prednisolone-treated rats slightly reduced the unfavorable effects of prednisolone on width of periosteal and endosteal osteoid and periosteal transverse growth in the tibia.     

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.     

Comparison of two doses of intravenous immunoglobulin after allogeneic bone marrow transplants.

Intravenous immunoglobulin has been used after bone marrow transplants to prevent infections and acute graft-versus-host disease. However, the minimum dose required for protection is unknown. This may have significant economic implications. A multicenter randomized clinical trial compared the impact of two intravenous immunoglobulin doses on systemic infections and acute graft-versus-host disease in transplant recipients. Either 250 mg/kg or 500 mg/kg was given weekly from day -8 to day +111. Multivariate analysis was used to assess the effect of dose and other risk factors on event-free survival, systemic infection, and acute graft-versus-host disease. The two-dose cohorts had similar event-free survival and infection frequencies. The higher dose was associated with less acute graft-versus-host disease (P = 0.03).