Androgen sensitivity of skeletal muscle: Nondependence on the motor nerve in the frog forearm

The effects of castration and of subsequent androgen administration on fiber size were investigated in several frog skeletal muscles. Four months after castration, cross-sectional cell area decreased by 70% and 14%, respectively, in the flexor carpi radialis and flexor carpi centralis muscles of the forearm and only by 2% in the ileo fibularis muscle of the thigh. Injection of testosterone propionate induced a hypertrophic response that reversed the effects of androgen deprivation; after 6 weeks, complete recovery to the control value was observed in all muscles selected. This sensitivity to the exogenous androgen was not altered by denervation; a similar hypertrophic evolution was seen in the denervated right muscles and in the homologous intact left muscles of the forearms. Using the myosin ATPase reaction, the muscle histochemical patterns were unchanged in all conditions tested. These results suggest that (i) a gradient of sensitivity to androgens exists in different frog muscles; (ii) androgens control the myofiber size but not the nerve-muscle organization as can be seen from the myofibrillar ATPase pattern; and (iii) the androgen sensitivity is not dependent on the motor nerve.     

Historical overview of analytical methods for the measurement of transthyretin.

The history of prealbumin dates back to the early forties and may be divided into three parts, based on a chronological and functional approach. The first part--the discovery and the identification of prealbumin--was essentially based on classical protein chemistry methods. The second--the demonstration of prealbumin as a thyroid hormone-binding protein (thyroxine-binding prealbumin)--has greatly benefited from isotopic techniques. The third one--establishing prealbumin as a nutritional marker--was a result of field studies on nutrition. The discovery of the role of prealbumin in retinol binding led to a change in its name, prealbumin becoming transthyretin. Finally, structural studies and mutation analysis of transthyretin in patients with amyloid neuropathy have opened a new area of research.     

Risk of Clostridium difficile-associated disease among patients receiving proton-pump inhibitors in a Quebec medical intensive care unit.

Our study was conducted to determine whether use of gastric acid-suppressive agents increased the risk of Clostridium difficile-associated disease (CDAD) in a medical intensive care unit of one of the first hospitals to be threatened by the current CDAD epidemic in Quebec, Canada. Our findings suggest that efforts to determine risk factors for CDAD should focus on other areas, such as older age and antibiotic use.     

Presence of specific 11C-meta-Hydroxyephedrine retention in heart, lung, pancreas, and brown adipose tissue.

(11)C-meta-Hydroxyephedrine (HED) is used in cardiac PET as an index of norepinephrine (NE) reuptake transporter (NET) density and synaptic NE levels. Whereas cardiac uptake is well documented, tracer retention in other tissues with rich noradrenergic innervation is unclear. Dysfunctional sympathetic nervous system (SNS) function in extracardiac metabolic storage tissues (i.e., adipose tissue and skeletal muscle) and endocrine organs contributes to several disorders. The aim of this study was to determine the potential of HED as an index of NE function in brown adipose tissue, lung, pancreas, skeletal muscle, and kidney by identifying NET-specific retention and determining the presence of radiolabeled metabolites. METHODS: Male Sprague-Dawley rats were administered HED and sacrificed at 30 min after tracer injection. Tissues were rapidly excised and counted for radioactivity, and relative tracer retention was quantified. Pretreatment with NET inhibitors established specific HED accumulation. The effect of elevated NE was tested by subcutaneous minipump NE infusion or inhibition of monoamine oxidase. Column-switch high-performance liquid chromatography (HPLC) was used to analyze the presence of radiolabeled metabolites in heart, brown adipose tissue, pancreas, and plasma. RESULTS: NET-specific retention was observed in heart, brown adipose tissue, lung, and pancreas but not in liver, skeletal muscle, or kidney. A dose-dependent response of HED accumulation to treatments elevating NE levels was established in tissues exhibiting specific uptake. At 30 min after tracer administration, HPLC analysis revealed 93%-95% of total radioactivity signal derived from unchanged HED in heart, pancreas, and brown adipose tissue compared with 61% +/- 8% unchanged HED in plasma. CONCLUSION: In addition to the heart, lung, pancreas, and brown adipose tissue exhibit specific and NE-responsive uptake of HED, supporting the potential for novel PET studies of SNS integrity in these tissues.     

Prospective, Double-Blind, Randomized, Parallel-Group, Dose-Ranging Study of Botulinum Toxin Type A in Men with Glabellar Rhytids

BACKGROUND: The effective dose for treating glabellar lines with botulinum toxin type A in men has not been studied adequately. OBJECTIVE: To compare the safety, efficacy, and duration of response of four doses of botulinum toxin type A on glabellar rhytids in men. METHODS: Eighty men were randomized to receive a total dose of either 20, 40, 60, or 80 U of botulinum toxin type A (BOTOX, BOTOX Cosmetic, or Vistabel, Allergan, Inc., Irvine, CA, USA) in the glabellar area. Glabellar lines were assessed at rest and maximum frown by a trained observer at baseline, 2 and 4 weeks, and monthly thereafter. Patients provided self-evaluations at the same visits. Adverse events were monitored throughout. RESULTS: The 40, 60, and 80 U doses of botulinum toxin type A were consistently more effective in reducing glabellar lines than the 20 U dose (duration, peak response rate, improvement from baseline). There was a dose-dependent increase in both the response rate at maximum frown and the duration of effect assessed by the trained observer. In addition, the participants reported a dose-dependent reduction in the ability to frown, improvement in their global assessment, and increased feelings of attractiveness, self-confidence, and satisfaction. The incidence of adverse events was not increased with higher doses. CONCLUSION: Male participants with glabellar rhytids benefit from starting doses of at least 40 U of botulinum toxin type A.     

Relationship between oxidative stress and essential hypertension.

This study investigated the association of blood pressure with blood oxidative stress-related parameters in normotensive and hypertensive subjects. A cross-sectional design was applied to 31 hypertensive patients and 35 healthy normotensive subjects. All subjects were men between the ages of 35 and 60 years. Exclusion criteria were obesity, dyslipidemia, diabetes mellitus, smoking and current use of any medication. All patients underwent 24-h ambulatory blood pressure monitoring and sampling of blood and urine. Antioxidant enzymes activity, reduced/oxidized glutathione ratio (GSH/GSSG), and lipid peroxidation (malondialdehyde) were determined in erythrocytes. Parameters measured in the plasma of test subjects were plasma antioxidant status, lipid peroxidation (8-isoprostane), plasma vitamin C and E, and the blood pressure modulators renin, aldosterone, endothelin-1 and homocysteine. Daytime systolic and diastolic blood pressures of hypertensives were negatively correlated with plasma antioxidant capacity (r=-0.46, p<0.009 and r=-0.48, p<0.007), plasma vitamin C levels (r=-0.53, p<0.003 and r=-0.44, p<0.02), erythrocyte activity of antioxidant enzymes, and erythrocyte GSH/GSSG ratio, with hypertensives showing higher levels of oxidative stress. Blood pressures showed a positive correlation with both plasma and urine 8-isoprostane. Neither plasma vitamin E nor the assessed blood pressure modulator levels showed significant differences between the groups or correlation with blood pressures. These findings demonstrate a strong association between blood pressure and some oxidative stress-related parameters and suggest a possible role of oxidative stress in the pathophysiology of essential hypertension.     

Tacrolimus Pharmacokinetics and Dose Monitoring After Lung Transplantation for Cystic Fibrosis and Other Conditions

In cystic fibrosis (CF), absorption of tacrolimus through the gastrointestinal tract may be impaired due to fat malabsorption. The aim of this pilot study was to compare tacrolimus pharmacokinetics and inter- and intrasubject variability of exposure in stable lung transplant recipients with and without CF, and to determine the best single-time predictors of exposure. The study included 11 lung transplant recipients with CF and 11 without CF who received tacrolimus twice daily. Blood samples were obtained predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 h postdose on 3 separate days within 1 week. Tacrolimus pharmacokinetics and inter- and intrasubject variability of exposure were similar in the two groups, though exposure-per-milligram-dose was approximately 50% lower in CF patients. Tacrolimus trough concentration did not accurately predict the area under the concentration curve (AUC(0-12)), but the concentration measured 3 h postdose (C(3)) was tightly correlated with the AUC(0-12) in both CF (r(2)= 0.86) and non-CF (r(2)= 0.92) patients. In summary, patients with CF have a higher tacrolimus oral clearance, but nonsignificant differences in short-term inter- and intrasubject variability of exposure compared to patients without CF. C(3) is tightly correlated with AUC(0-12) in lung transplant recipients with and without CF.