Positive selection for loss-of-function tat mutations identifies critical residues required for TatA activity.
We have studied the effect of salmeterol on both P. aeruginosa interactions with the mucosa of nasal turbinate organ cultures and on pyocyanin-induced (20 microg/ml) and elastase-induced (100 microg/ml) damage to nasal epithelial cells. Organ cultures were exposed to salmeterol either by preincubation with 4 x 10(-7) M salmeterol for 30 min or by pipetting 20 microl of 4 x 10(-7) M salmeterol onto the organ culture surface immediately prior to bacterial inoculation. Infected organ cultures (8 h) had significantly (p < or = 0.01) increased epithelial damage, and P. aeruginosa was predominantly associated with damaged epithelium and mucus. Salmeterol significantly (p < or = 0.02) reduced epithelial damage caused by infection and the total number of adherent bacteria (p < or = 0.05), but bacterial distribution on the mucosa was unchanged. Nasal epithelial cells incubated with pyocyanin (20 microg/ml) or elastase (100 microg/ml) for 3 h had significantly (p < or = 0.05) increased cytoplasmic blebbing and mitochondrial damage versus control values. Elastase also significantly (p < or = 0.05) increased cell projection and reduced the level of ciliation. Cells preincubated with salmeterol (2 x 10(-7) M) showed a significant reduction in some features of cell damage caused by both toxins, which was inhibited by the beta2-adrenoceptor antagonist propranolol. Our results indicate that salmeterol reduces P. aeruginosa-induced damage to both organ culture and nasal epithelium.
The 31 patients enrolled in each treatment arm had similar baseline demographic and clinical characteristics. At 1 hour after the intervention, the HS group demonstrated significantly less improvement in the median Respiratory Assessment Change Score compared with the NS group (HS, -1 [interquartile range, -5 to 1] vs. NS, -5 [interquartile range, -6 to -2]; P = .01). There were no significant differences in heart rate, oxygen saturation, hospitalization rate, or other outcomes. There were no adverse events.
Various co-polymeric hydrogels for transdermal delivery of salbutamol sulphate were synthesized using 2-hydroxyethyl methacrylate (HEMA), methacrylic acid (MAA) and N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) in the presence of ammonium persulphate (APS) and N,N,N',N'-tetramethylethylenediamine (TEMED) as redox free radical initiator and ethyleneglycol dimethacrylate (EGDMA) as a cross-linker. The synthesized co-polymeric hydrogels were characterized using FT-IR spectral studies and swelling studies. It was observed that percentage swelling of co-polymeric hydrogel increased with the increasing concentration of DMAPMA and methacrylic acid. Salbutamol sulphate, a well-known vasodilator, was labeled with (99m)Tc(technetium) and loaded on circular discs of various hydrogels. In vitro permeation of radiolabelled salbutamol sulphate was carried out using a Franz diffusion cell in phosphate-buffered saline (PBS, pH 7.4) as dissolution medium through mice skin. It was observed that drug release from the co-polymeric hydrogel carriers increased on increasing the amount of DMAPMA in the polymeric carriers, while it decreased on increasing the amount of MAA content. The local toxicity studies of DMAPMA-containing hydrogel patches were carried out in rabbits. Drug-loaded patches applied on rabbit skin showed no toxicity, even after 1 week of studies.
Although inhaled beta2-agonists are in widespread use, several reports question their potential arrhythmogenic effects. The purpose of this study was to evaluate the cardiac electrophysiologic effects of a single, regular dose of an inhaled beta2-agonist in humans.
In a double-blind double-dummy crossover study, the effects of salbutamol dry powder inhaled from Salbutamol cyclocaps Pharbita 0.4 mg with the Pharbita inhaler and from a reference product were compared. On the first trial day, a single dose of one of the two preparations was administered, and 2 days later a single dose of the another preparation was administered, in random order. The effects on lung function (FEV1) were monitored from 15 to 360 min after administration. For both products the increase in FEV1 with reference to baseline values was statistically highly significant. There was no significant difference between the products.
Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, food allergy, and urticaria are common in general pediatric practice. This review highlights several significant advances in pediatric allergy over the past year, focusing on asthma and atopic dermatitis.
This randomized, controlled study compared the ability to mobilize and collect an optimal target yield of 5 x 10(6) CD34+ cells/kg using stem cell factor (SCF; 20 microg/kg/day) plus filgrastim (G-CSF; 10 microg/kg/day) vs filgrastim alone (10 microg/kg/day) in 102 patients diagnosed with non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD), who were prospectively defined as being heavily pretreated. Leukapheresis began on day 5 of cytokine administration and continued daily until the target yield was reached, or until a maximum of five leukaphereses had been performed. Compared with the filgrastim-alone group (n = 54), the SCF plus filgrastim group (n = 48) showed an increase in the proportion of patients reaching the target yield within five leukaphereses (44% vs 17%, P = 0.002); reduction in the number of leukaphereses required to reach the target yield (P = 0.003); reduction in the proportion of patients failing to reach a minimum yield of 1 x 10(6) CD34+ cells/kg to proceed to transplant (16% vs 26%, P = NS); increase in the median yield of CD34+ cells per leukapheresis (0.73 x 10(6)/kg vs 0.48 x 10(6)/kg, P = 0.04); and an increase in the median total CD34+ cells collected within five leukaphereses (3.6 x 10(6)/kg vs 2.4 x 10(6)/kg, P = 0.05). All patients receiving SCF were premedicated (antihistamines and albuterol), and treatment was generally well tolerated. Five patients experienced severe mast cell-mediated reactions, none of which were life-threatening. In this study of heavily pretreated lymphoma patients, SCF plus filgrastim was more effective than filgrastim alone for mobilizing PBPC for harvesting and transplantation after high-dose chemotherapy.