Elevated Serum Cytokines and Trichomonas vaginalis Serology at Diagnosis Are Not Associated With Higher Gleason Grade or Lethal Prostate Cancer

Background

Inflammation and infections have been associated with prostate cancer progression. We assessed whether elevated serum cytokines or T. vaginalis seropositivity at the time of diagnosis was associated with higher grade or lethal prostate cancer.

Dermal absorption of niclosamide in rats and minipigs

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.     

Exercise rapidly increases eukaryotic elongation factor 2 phosphorylation in skeletal muscle of men

Protein synthesis in skeletal muscle is known to decrease during contractions but the underlying regulatory mechanisms are unknown. Here, the effect of exercise on skeletal muscle eukaryotic elongation factor 2 (eEF2) phosphorylation, a key component in protein translation machinery, was examined. Eight healthy men exercised on a cycle ergometer at a workload eliciting ∼67% peak pulmonary oxygen consumption     with skeletal muscle biopsies taken from the vastus lateralis muscle at rest as well as after 1, 10, 30, 60 and 90 min of exercise. In response to exercise, there was a rapid (i.e. < 1 min) 5- to 7-fold increase in eEF2 phosphorylation at Thr56 that was sustained for 90 min of continuous exercise. The in vitro activity of skeletal muscle eEF2 kinase was not altered by exercise indicating that the increased activity of eEF2 kinase to eEF2 is not mediated by covalent mechanisms. In support of this, the increase in AMPK activity was temporally unrelated to eEF2 phosphorylation. However, skeletal muscle eEF2 kinase was potently activated by Ca²⁺–calmodulin in vitro , suggesting that the higher eEF2 phosphorylation in working skeletal muscle is mediated by allosteric activation of eEF2 kinase by Ca²⁺ signalling via calmodulin. Given that eEF2 phosphorylation inhibits eEF2 activity and mRNA translation, these findings suggest that the inhibition of protein synthesis in contracting skeletal muscle is due to the Ca²⁺-induced stimulation of eEF2 kinase.     

Postoperative splinting for isolated digital nerve injuries in the hand.

Digital nerve injuries in the hand are common and can result in significant impairment and functional restriction. Despite this, there is relatively little literature, particularly with respect to postoperative rehabilitation. Splinting after repair, purported to protect the repaired nerve from excessive stretch is still commonly used. Recent cadaveric studies indicate postoperative rehabilitation is not necessary with resection up to 2.5mm. A randomized controlled trial was therefore undertaken to determine whether splinting after isolated 5th degree digital nerve transection is in fact necessary. Twenty-six subjects were recruited over a two-year period and randomized to either three weeks of hand-based splinting or free active motion. ANCOVA indicated no differences in sensibility at six months between the two groups. Subjects also reported their greatest functional limitations were because of hyperesthesia. Although this study is underpowered, these limited results suggest splinting may not be required postoperatively.     

Renal function during onset of carbachol-induced hypertension in conscious rats

This study evaluated the changes in renal function that occur during the early phases of chronic infusion of carbachol into the lateral ventricle in conscious rats. Infusion of 1.0 micrograms/h of carbachol i.c.v. resulted in a prompt pressor response with mean arterial pressure rising 20 mm Hg within 15 min. The pressure remained elevated for the duration of a 2-hour infusion. Carbachol infusion at 0.5 micrograms/h induced a similar elevation in blood pressure, but the onset was delayed, reaching significance only after 30-60 min. The higher dose of carbachol was associated with a marked and sustained natriuresis, with sodium excretion increasing from 2.1 +/- 0.3 to 5.3 +/- 1.0 microEq/100 g min after 2 h, compared to 2.0 +/- 0.5 and 1.8 +/- 0.3 microEq/100 g min in vehicle-infused control animals. Sodium excretion did not change significantly in animals infused with carbachol at 0.5 microgram/h. There were no significant changes in glomerular filtration rate in any of the groups. Plasma levels of atrial natriuretic peptide (ANP) were not altered significantly by ventricular infusion of carbachol (188 +/- 99 before vs. 83 +/- 17 pg/ml after infusion). It is concluded that the pressor response to central carbachol infusion is not dependent on retention of sodium and water. The natriuresis observed with carbachol infusion can be dissociated from the pressor response, and is not mediated by ANP.