Regulation of secretion in Clara cells: studies using the isolated perfused rat lung.

Previous studies from our laboratory indicated that both beta-adrenergic and cholinergic agents stimulate in vivo secretion by rat bronchiolar Clara cells. Those studies also provided support for an in-series beta-adrenergic-cholinergic stimulation of secretion. To further explore the regulation of secretion in Clara cells, and to do it in the absence of systemic influences, we have used the isolated ventilated perfused rat lung. We have again used morphometry and electron microscopy to assess secretion by measuring the volume density (fraction of cell volume) of the secretory granules of bronchiolar Clara cells. We found that in the isolated perfused lung, as in the intact animal, isoproterenol stimulated secretion in Clara cells and that this effect was blocked by the beta-adrenergic antagonist propranolol. Pilocarpine, unlike its action in the intact animal, did not stimulate secretion in the isolated lung; rather it inhibited the secretory effect of isoproterenol. Increased tidal-volume ventilation stimulated secretion; propranolol did not block this effect. Analogs of cyclic (c)AMP and of cGMP also stimulated secretion by Clara cells. These findings indicate that there are at least two mechanisms by which Clara cells can be stimulated to secrete. One seems to be beta-adrenergic-cAMP mediated but the triggering event is unknown. The other is initiated by increased tidal volume and cGMP may be involved in the intracellular mediation of this stimulatory event. Finally, we found evidence of beta-adrenergic (stimulatory) -cholinergic (inhibitory antagonism in the regulation of secretion in Clara cells.     

Efficacy and safety of a novel once-daily extended-release ciprofloxacin tablet formulation for treatment of uncomplicated urinary tract infection in women

The efficacy and safety of a novel once-daily extended-release ciprofloxacin (ciprofloxacin ER) 500-mg dose were compared with those of an immediate-release ciprofloxacin (ciprofloxacin IR) 250-mg twice-daily dose, each administered orally for 3 days in the treatment of acute uncomplicated urinary tract infection (uUTI) in women. Adult female outpatients (mean age, 39 years) with clinical signs and symptoms of acute uUTI and a positive pretreatment urine culture (> or =10(5) CFU/ml) were enrolled in a multicenter, randomized, double-blind, noninferiority trial. Patients were assessed at a test-of-cure visit (4 to 11 days posttreatment) and a late-posttreatment visit (4 to 6 weeks posttreatment) for microbiological and clinical outcomes and safety. The primary efficacy endpoint and microbiological eradication rate at the test-of-cure visit in the ciprofloxacin ER group (254/272; 93.4%) were noninferior to those in the ciprofloxacin IR group (225/251; 89.6%) (95% confidence interval [CI] of difference, -0.99%, 8.59%). Clinical-cure rates at the test-of-cure visit were 85.7% (233/272) for ciprofloxacin ER and 86.1% (216/251) for ciprofloxacin IR (95% CI of difference, -6.37%, 5.57%). At the late-posttreatment visit, microbiological and clinical outcomes were similar for the two treatments and consistent with test-of-cure results. Both treatments were well tolerated, but the frequencies of nausea and diarrhea were lower in the ciprofloxacin ER group than in the ciprofloxacin IR group (nausea, ER, 0.6%; IR, 2.2%; P = 0.033; diarrhea, ER, 0.2%; IR, 1.4%; P = 0.037). Once-daily ciprofloxacin ER was safe, effective, and noninferior to twice-daily ciprofloxacin IR in the treatment of acute uUTI. Additionally, ciprofloxacin ER was associated with significantly reduced frequencies of nausea and diarrhea.     

Nd-YAG Laser Treatment for Tracheobronchial Obstruction

The Nd-YAG laser has good tissue penetration and coagulation effects thus has become an important weapon for photoresection of tracheobronchial obstructive lesions since 1980.Treatment of benign lesions including benign tumors and scar tissues using the Nd-YAG laser has good results. In the treatment of malignant tumors however, it has a lower effectivity rate when compared to benign lesions. From July 1984 to September 1995, a total of 65 patients were treated with Nd-YAG laser for tracheobronchial obstruction. There were 32 (49%) malignant tumors and 33 (51%) benign lesions. 116 resections were performed in 48 patients using the non-contact Nd-YAG laser (MBB, Medilas 2) before 1992. Thereafter, another 41 resections were performed in 17 cases using contact Nd-YAG laser (SLT, CL-X). The overall effectivity rate was 60%. The effectivity rate for benign lesions was 81.3% and 39.4% for malignant tumor. The effectivity rate between non-contact and contact Nd-YAG laser was not significantly different.     

Binding of Chemotactic Collagen-Derived Peptides to Fibroblasts: THE RELATIONSHIP TO FIBROBLAST CHEMOTAXIS

We previously showed that collagen, α-chains, and collagen-derived peptide fragments induce chemotactic migration of human fibroblasts in vitro. We now describe biochemical and immunological evidence showing there are binding sites for collagen peptides on fibroblast membranes.     

Importance of group X-secreted phospholipase A2 in allergen-induced airway inflammation and remodeling in a mouse asthma model

Arachidonic acid metabolites, the eicosanoids, are key mediators of allergen-induced airway inflammation and remodeling in asthma. The availability of free arachidonate in cells for subsequent eicosanoid biosynthesis is controlled by phospholipase A(2)s (PLA(2)s), most notably cytosolic PLA(2)-alpha. 10 secreted PLA(2)s (sPLA(2)s) have also been identified, but their function in eicosanoid generation is poorly understood. We investigated the role of group X sPLA(2) (sPLA(2)-X), the sPLA(2) with the highest in vitro cellular phospholipolysis activity, in acute and chronic mouse asthma models in vivo. The lungs of sPLA(2)-X(-/-) mice, compared with those of sPLA(2)-X(+/+) littermates, had significant reduction in ovalbumin-induced infiltration by CD4(+) and CD8(+) T cells and eosinophils, goblet cell metaplasia, smooth muscle cell layer thickening, subepithelial fibrosis, and levels of T helper type 2 cell cytokines and eicosanoids. These data direct attention to sPLA(2)-X as a novel therapeutic target for asthma.     

Decreased elimination of unbound prazosin in the presence of alpha 1-acid glycoprotein in the rat in vivo

The kinetics of unbound prazosin under constant i.v. infusion (800 ng/kg/min) and after i.v. bolus (160 micrograms/kg) were determined in control rats and in rats pretreated with human alpha 1-acid glycoprotein (AAG). Administration of 40 and 100 mg/kg of AAG decreased the unbound fraction in plasma of prazosin from 0.238 to 0.175 and 0.090, respectively. Administration of 40 mg/kg of AAG decreased the clearance of prazosin with respect to unbound drug (CLu) on the average by 40%. There was no statistically significant difference in the decrease of CLu between animals given constant infusions and i.v. bolus of prazosin. Increasing the administered dose of AAG from 40 to 100 mg/kg caused no further decrease in CLu. Because prazosin is a low-to-medium extraction ratio compound in the rat, this decrease in CLu indicates that AAG has an inhibitory effect on the elimination of prazosin that goes beyond a simple protein binding effect. The apparent volume of distribution of unbound drug, steady state, VUss, decreased from 12.4 to 7.7 liters/kg, and the red blood cell/plasma water concentration ratio decreased from 9.2 to 4.0 after administration of AAG. The possible mechanisms for the observed effects are discussed.     

A double-blind ambulatory blood pressure monitoring study of the efficacy and tolerability of once-daily telmisartan 40 mg in comparison with losartan 50 mg in the treatment of mild-to-moderate hypertension in Taiwanese patients

Ambulatory blood pressure monitoring (ABPM) was used to compare the efficacy and tolerability of once-daily telmisartan 40 mg and once-daily losartan 50 mg in Taiwanese patients with mild-to-moderate essential hypertension in a randomised, double-blind, double-dummy, parallel-group study. The initial 2-week placebo run-in phase was followed by randomisation to treatment with telmisartan 40 mg (n = 31) or losartan 50 mg (n = 30) for 6 weeks. The reduction in 18- to 24-h mean (SE) ambulatory diastolic blood pressure (DBP) from baseline was significantly greater with telmisartan 40 mg (-12.1 +/- 1.6 mmHg, p = 0.036) than with losartan 50 mg (-7.0 +/- 1.8 mmHg). The reduction in 18- to 24-h mean (SE) ambulatory systolic blood pressure (SBP) from baseline was also greater with telmisartan 40 mg (-16.0 +/- 2.4 mmHg) than with losartan 50 mg (-11.8 +/- 2.7 mmHg), but did not achieve statistical significance. Telmisartan was well tolerated; no serious adverse events occurred.     

Association of metabolic syndrome, atherosclerosis risk factors, sex hormones in ED in aboriginal Taiwanese

The overall prevalence of metabolic syndrome (MS) in aboriginal male Taiwanese is very high. Many studies have found that those with cardiovascular disease and MS have a significantly higher risk of ED. In this study, we attempted to find the correlation among MS risk factor, atherosclerosis risk factors and low serum testosterone in relation to the development of ED. This was a cross-sectional study of 238 cases, and collected data included demographic data, lifestyle questionnaires, sexual desire scale, sexual satisfaction scale and International Index of Erectile Function (IIEF) questionnaire. Among our 238 subjects, 146 had MS (61.3%) and 114 subjects with MS had ED (85.7%). Using age-adjusted multivariate logistic regressive analysis, this study showed that aboriginal males with ED had a significantly higher prevalence of MS (OR=12.02, 95% confidence intervals (CI): 6.33-22.83, P<0.001). Among the MS components, abnormal fasting blood sugar was the most significantly independent factor for ED in aboriginal males (OR=8.94, 95% CI: 4.71-16.97, P<0.001). The presence of MS had a significant correlation with lower IIEF-5 scores, lower sexual desire scores, lower testosterone serum level (P<0.01) and abnormal interleukin-6 (IL-6) and high sensitivity C-reactive protein (HsCRP). The results of this study support the idea that MS, low serum testosterone and HsCRP may predict ED in aboriginal Taiwanese males. Further studies with population-based and longitudinal design should be conducted to confirm this finding and design to compare rates of ED in aboriginal men with MS.     

Improvement of Nonalcoholic Fatty Liver Disease After Bariatric Surgery in Morbidly Obese Chinese Patients

Background

Obesity is a risk factor for nonalcoholic fatty liver disease (NAFLD), which appears to improve after weight loss induced by bariatric surgery in Western countries. The present study aims to determine the alterations of clinical measurements and liver histology of NAFLD after bariatric surgery in morbidly obese Chinese patients.

Methods

Between November 2006 and December 2007, 21 morbidly obese patients receiving intra-operative liver biopsy and follow-up liver biopsy 1?year after laparoscopic Roux-en-Y gastric bypass were enrolled. NAFLD activity score (NAS) and fibrosis stage were histologically evaluated.

Results

The mean body mass index fell from 43.8?±?7.5 to 28.3?±?4.6?kg/m² (P?P?P?<?0.01), but not aspartate aminotransferase (P?=?0.66). Histological improvement was noted in NAS (P?P?P?P?=?0.02). Pre-operatively, 4 (19.0%), 11 (52.4%), and 6 (28.6%) patients were found to have NAS ?R5, 3 or 4, and ?Q2, respectively. All patients had NAS ?Q2 after surgery. Fibrosis stage also showed significant improvement (P?Conclusions Bariatric surgery can achieve a dramatic improvement of NAFLD both biochemically and histologically in morbidly obese Chinese patients.