Numbers of coliforms, Escherichia coli, F-RNA phage, rotavirus, bovine enteric calicivirus and presence of non-O157 STEC on commercial vacuum packaged beef.

The numbers of coliforms, Escherichia coli, F-RNA coliphages, bovine enteric calicivirus (BEC) and rotavirus (RV) and presence of non-O157 shiga toxigenic E. coli (STEC) were determined on commercial vacuum packaged beef subprimals at the retail level from swabs obtained from the entire surfaces of 150 cuts that originated from federally and provincially registered plants. The prevalence and log mean numbers of E. coli were higher in provincially registered plants than in federally registered plants; 64% vs 20%, respectively, and -0.3 vs -1.22 log cfu/100 cm(2), respectively. In contrast, the prevalence and mean log numbers of F-RNA coliphages were lower for the provincially registered plants than for the federally registered plants; 31% vs 68% and -0.86 vs -0.13 log cfu/100 cm(2), respectively. One E. coli sample tested positive for stx2 and eae. F-RNA coliphages associated with human origin (GII/GIII) were detected in 12% and 30% of samples that originated from provincially and federally registered plants, respectively. RV RNA was detected in 4% of samples while BEC RNA was not detected. Although the infectivity of RV is unknown, the presence of viable F-RNA coliphages suggests that consumers could potentially be at risk when consuming undercooked meat that is contaminated with RV.

Impact of riparian zone protection from cattle on nutrient, bacteria, F-coliphage, and loading of an intermittent stream.

This 5-yr study compared, via an upstream-downstream experimental design, nutrient and microbial water quality of an intermittent stream running through a small pasture (∼2.5 animals ha) where cattle are restricted from the riparian zone (restricted cattle access [RCA]) and where cattle have unrestricted access to the stream (unrestricted cattle access [URCA]). Fencing in the RCA excluded pasturing cattle to within ∼3 to 5 m of the stream. Approximately 88% (26/32) of all comparisons of mean contaminant load reduction for lower, higher, and all stream flow conditions during the 5-yr study indicated net contaminant load reductions in the RCA; for the URCA, this percentage was 38% (12/32). For all flow conditions, mean percent load reductions in the RCA for nutrients and bacteria plus F-coliphage were 24 and 23%, respectively. These respective percentages for the URCA were -9 and -57% (positive values are reductions; negative values are increases). However, potentially as a result of protected wildlife habitat in the RCA, the mean percent load reduction for for "all flow" was -321% for the RCA and 60% for the URCA; for , these respective percentages were -209% (RCA) and 73% (URCA). For "all flow" situations, mean load reductions for the RCA were significantly greater ( < 0.1) than those from the URCA for NH-N, dissolved reactive phosphorus (DRP), total coliform, , and . For "high flow" situations, mean load reductions were significantly greater for the RCA for DRP, total coliform, and . For "low flow" conditions, significantly greater mean load reductions were in favor of the RCA for DRP, total P, total coliforms, fecal coliforms, , and . In no case were mean pollutant loads in the URCA significantly higher than RCA pollutant loads. Restricting pasturing livestock to within 3 to 5 m of intermittent streams can improve water quality; however, water quality impairment can occur if livestock have unrestricted access to a stream.

What is the effectiveness of surgical and non-surgical therapies in the treatment of ischemic priapism in patients with sickle cell disease? A systematic review by the EAU Sexual and Reproductive Health Guidelines Panel.

Sickle cell disease (SCD) is an inherited hemoglobin disorder characterized by the occlusion of small blood vessels by sickle-shaped red blood cells. SCD is associated with a number of complications, including ischemic priapism. While SCD accounts for at least one-third of all priapism cases, no definitive treatment strategy has been established to specifically treat patients with SC priapism. The aim of this systematic review was to assess the efficacy and safety of contemporary treatment modalities for acute and stuttering ischemic priapism associated with SCD. The primary outcome measures were defined as resolution of acute priapism (detumescence) and complete response of stuttering priapism, while the primary harm outcome was as sexual dysfunction. The protocol for the review has been registered (PROSPERO Nr: CRD42020182001), and a systematic search of Medline, Embase, and Cochrane controlled trials databases was performed. Three trials with 41 observational studies met the criteria for inclusion in this review. None of the trials assessed detumescence, as a primary outcome. All of the trials reported a complete response of stuttering priapism; however, the certainty of the evidence was low. It is clear that assessing the effectiveness of specific interventions for priapism in SCD, well-designed, adequately-powered, multicenter trials are strongly required.

Dyslipidaemia is associated with testosterone, oestradiol and androgen receptor CAG repeat polymorphism in men with type 2 diabetes.

OBJECTIVE: There is a high prevalence of low testosterone and dyslipidaemia in men with type 2 diabetes. The androgen receptor CAG repeat polymorphism (AR CAG) affects receptor transcriptional activity (the shorter repeats the more sensitive AR) and is associated with androgenic parameters and obesity. This study describes the relationships between testosterone, AR CAG and serum lipids in men with type 2 diabetes. DESIGN AND PATIENTS: Cross-sectional study of men with type 2 diabetes in a District General Hospital Diabetes Centre. MEASUREMENTS: Correlation between testosterone, AR CAG and serum lipids. RESULTS: HDL cholesterol (HDL-C) correlated with total testosterone (TT) (r = 0·251, P < 0·001), bioavailable testosterone (BT) (r = 0·19, P = 0·001), free testosterone (FT) (r = 0·165, P = 0·005) and sex hormone-binding globulin (SHBG) (r = 0·147, P = 0·014). HDL-C did not correlate with oestradiol, but men with the lowest quartile of oestradiol had lower HDL-C compared to highest quartile (P = 0·046). Triglycerides correlated negatively with TT (r = -0·195, P = 0·001), BT (r = -0·148, P = 0·013) and SHBG (-0·14, P = 0·019) but not with FT or oestradiol. Total and LDL cholesterol (LDL-C) correlated negatively with oestradiol (r = -0·121, P = 0·05) but not with testosterone or SHBG. One-way anova testing across four quartiles of AR CAG showed a trend to alteration in HDL-C across groups of AR CAG (P = 0·08). HDL-C was significantly higher in men with the longest AR CAG compared with the shortest (1·19 vs 1·08 mmol/l, P = 0·02). CONCLUSIONS: Lower testosterone and oestradiol levels in men with diabetes are associated with an adverse lipid profile. Shorter AR CAG is associated with low HDL-C and testosterone. The paradox that HDL-C is associated with low testosterone levels and a more active AR may suggest divergent effect of testosterone on HDL-C via genomic vs nongenomic mechanisms.

Copper oxide-based cathode for direct NADPH regeneration.

Nearly a fourth of all enzymatic activities is attributable to oxidoreductases, and the redox reactions supported by this vast catalytic repertoire sustain cellular metabolism. In many biological processes, reduction depends on hydride transfer from either reduced nicotinamide adenine dinucleotide (NADH) or its phosphorylated derivative (NADPH). Despite longstanding efforts to regenerate NADPH by various methods and harness it to support chemoenzymatic synthesis strategies, the lack of product purity has been a major deterrent. Here, we demonstrate that a nanostructured heterolayer Ni-Cu2O-Cu cathode formed by a photoelectrochemical process has unexpected efficiency in direct electrochemical regeneration of NADPH from NADP+. Remarkably, two-thirds of NADP+ was converted to NADPH with no measurable production of the inactive (NADP)2 dimer and at the lowest reported overpotential [- 0.75 V versus Ag/AgCl (3 M NaCl) reference]. Sputtering of nickel on the copper-oxide electrode nucleated an unexpected surface morphology that was critical for high product selectivity. Our results should motivate design of integrated electrolyzer platforms that deploy this heterogeneous catalyst for direct electrochemical regeneration of NADH/NADPH, which is central to design of next-generation biofuel fermentation strategies, biological solar converters, energy-storage devices, and artificial photosynthesis.

Stink of Stinkpot Turtle Identified: ohgr-Phenylalkanoic Acids.

The exocrine secretion of the "stinkpot turtle," Sternotherus odoratus, discharged by the animals in response to disturbance, contains four omega-phenylalkanoic acids (phenylacetic, 3-phenylpropionic, 5-phenylpentanoic, and 7-phenylheptanoic). The last two of these are new natural products. The first two are powerfully malodorous and responsible for the stench of the fluid. Lesser components, including several aliphatic acids, are also present. Only a few milligrams of secretion are discharged by a turtle at any one time. Although bioassays with fish suggest that the secretion has the potential to serve as a feeding deterrent to predators, it is argued that Sternotherus does not ordinarily discharge enough fluid to effect this action and may employ its secretion only as an aposematic signal that warns predators of its more generalized undesirability.

Sex pheromones in snakes.

The majority of pheromones identified to date are insect pheromones, which are volatile in nature. Identification of nonvolatile pheromones have been relatively rare, especially in vertebrates. Male and female garter snakes use pheromones to mediate sexual behavior. The female sex attractiveness pheromone of the Canadian red-sided garter snake, Thamnophis sirtalis parietalis, consists of a novel series of nonvolatile saturated and monounsaturated long-chain methyl ketones, whereas the male sex recognition pheromone contains squalene. These compounds were isolated, identified, and partially synthesized, and field tests show them to be biologically active.

Testosterone acts as an efficacious vasodilator in isolated human pulmonary arteries and veins: evidence for a biphasic effect at physiological and supra-physiological concentrations.

BACKGROUND: Testosterone is recognized to elicit vasodilatation in numerous vascular beds, however to date no study has investigated whether testosterone has this effect in the human pulmonary vasculature. AIM: To determine whether isolated human pulmonary arteries and veins dilate in response to testosterone and whether the response differs in relation to gender, endothelial function or location with the pulmonary vasculature. METHODS: Intralobar pulmonary arteries [no.=44, diameter =581 (349) microm] and veins [no.=27, diameter =573 (302) microm] were dissected from lobectomy samples obtained from male and female patients [no.=40, age =69 (8) yr]. Vessels were mounted in an automated wire myograph, bathed in physiological saline at 37 C and pH 7.4, and loaded to their in vivo pressure. Vessels were preconstricted with noradrenaline (10 microM) and exposed to acetylcholine (1 microM) to assess endothelial function, washed and then preconstricted with potassium chloride (1-100 mM) followed by either cumulative concentrations of testosterone (1 nM-100 microM) or ethanol vehicle (<0.1%). RESULTS: Significant marked vasodilatation was seen in all vessels, irrespective of size, gender and endothelial function at micromolar concentrations. Testosterone triggered significant vasodilatation at concentrations > or = 10 nM in pulmonary arteries obtained from males, a response which was not observed in vessels from females. The maximal response at 100 microM was also significantly greater in male pulmonary arteries. Significant vasodilatation was only observed at physiological (nM) concentrations in pulmonary resistance arteries and pulmonary arteries with good endothelial function. CONCLUSION: Testosterone acts as an efficacious vasodilator in the human pulmonary vasculature, with dilatation observed at physiological concentrations in the male arterial resistance bed, dependent on the presence of an intact endothelium.

Changes in the proteome of Escherichia coli during growth at 15 degrees C after incubation at 2, 6 or 8 degrees C for 4 days.

For better understanding of the complex behaviour of Escherichia coli at chiller temperatures, log phase E. coli grown at 15 degrees C were incubated at 8, 6, or 2 degrees C for 4 days, and were then incubated at 15 degrees C for 12 h. Cultures were sampled after incubation at the lower temperatures, and during subsequent incubation at 15 degrees C. Proteins extracted from the samples were separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Spots of 45 previously identified proteins that were differentially expressed at 15 or < or =8 degrees C were quantified by image analysis. After incubation at 8 or 6 degrees C for 4 days cells were growing with or without formation of elongated cells (filaments), respectively, but growth did not occur at 2 degrees C. In cells incubated at 8 or 6 degrees C proteins associated with the stress response and energy generation were upregulated and proteins associated with protein synthesis were downregulated, while protein levels in cells incubated at 2 degrees C were little changed. When cells were then incubated at 15 degrees C, the levels of differentially expressed proteins in cells that had been incubated at 8 or 6 degrees C decreased or increased towards the levels found in cells growing at 15 degrees C, but some proteins were still under or over expressed after 12 h. In cells incubated at 15 degrees C after incubation at 2 degrees C, the levels of many of the proteins declined but the levels of proteins associated with protein synthesis increased. The findings indicate that the physiological states of log phase E. coli incubated at < or =2 degrees C or at higher chiller temperature are different, but that for both states incubation at an above chiller temperature for >3 generations is required before protein levels adjusted to those usual for the higher temperature. Cells in these different physiological states may respond differently to other stresses encountered during warming of chilled foods.

Design and characterization of an electromagnetic probe for distinguishing morphological differences in soft tissues.

We present a method for designing and optimizing an in-house designed electromagnetic probe for distinguishing morphological differences in biological tissues. The probe comprises concentric multi-wound coils, the inner being the primary coil and the outer being the detector coil. A time-varying voltage is imposed on the primary coil, resulting in an induced current in the detector coil. For highly conductive samples, eddy currents are induced in the sample and inductively couple with the electromagnetic probe. However, in weakly conducting samples, the primary coupling mechanism is found to be capacitive though there can be a non-negligible inductive component. Both the mutual inductive coupling and the capacitive coupling between the sample and the probe are detected as a change in the induced voltage of the detector coil using lock-in detection. The induced voltage in the detector coil is influenced more by the morphological structure of the specimen rather than by changes in electrical conductivity within different regions of the sample. The instrument response of the lock-in amplifier is also examined with simulated input voltage signals to relate its output to specific changes in inductive and capacitive coupling, in order to relate sample characteristics to a single voltage output. A circuit element model is used to interpret the experimental measurements. It is found that the sensitivity of the measurement for a given set of probe characteristics (resistances, inductances, and capacitances) can be optimized by adding a small amount of capacitance in the external circuit in parallel with the detector coil. Illustrative measurements are presented on animal (porcine and bovine) tissue and on human liver tissue containing a metastatic tumor to demonstrate the capabilities of the probe and measurement method in distinguishing different tissue types despite having similar electrical conductivities. Since biological tissues are multi-scale, heterogeneous materials comprising regions of differing conductivity, permittivity, and morphological structure, the electromagnetic method presented here has the potential to examine structural variations in tissue undergoing physical changes due to healing or disease.

A new 2% testosterone gel formulation: a comparison with currently available topical preparations.

Testosterone gel formulations have become a popular testosterone replacement therapy in patients with hypogonadism since their advent in the year 2000. The gel formulations restore testosterone levels to mid-normal physiological levels (14-17.5 nmol/L) as early as within 24 h, and help alleviate the signs and symptoms of testosterone deficiency, thereby leading to an improved quality of life. Although testosterone gels have a favourable efficacy and safety profile as compared to injectable and patch formulations, risk of secondary exposure poses a challenge. Approved testosterone topical formulations include Tostrex® (Tostran® , Fortesta® ), Androgel® (Testogel® ), Testim® and Axiron® (solution), which have a favourable efficacy profile and positively impacted patient-reported outcome(s). Besides, Testavan, which is a 2% testosterone gel, is under registration in Europe and already approved in Australia in May 2017. Testavan uses a novel hydroalcoholic and highly viscous topical formulation. This product comes with a metered dose dispenser and a cap applicator that allows a hands-free application for precise dispensing and application. The present article provides a comprehensive review of pharmacokinetic, tolerability and safety profile of the testosterone gels available in the market along with the new 2% testosterone gel, Testavan.

The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes.

OBJECTIVE: Serum testosterone levels are known to inversely correlate with insulin sensitivity and obesity in men. Furthermore, there is evidence to suggest that testosterone replacement therapy reduces insulin resistance and visceral adiposity in type 2 diabetic men. Adipocytokines are hormones secreted by adipose tissue and contribute to insulin resistance. We examined the effects of testosterone replacement treatment on various adipocytokines and C-reactive protein (CRP) in type 2 diabetic men. DESIGN: Double-blinded placebo-controlled crossover study in 20 hypogonadal type 2 diabetic men. Patients were treated with testosterone (sustanon 200 mg) or placebo intramuscularly every 2 weeks for 3 months in random order followed by a washout period of 1 month before the alternate treatment phase. METHODS: Leptin, adiponectin, resistin, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and CRP levels were measured before and after each treatment phase. Body mass index (BMI) and waist circumference were also recorded. RESULTS: At baseline, leptin levels significantly correlated with BMI and waist circumference. There was a significant inverse correlation between baseline IL-6 and total testosterone (r=-0.68; P=0.002) and bioavailable testosterone levels (r=-0.73; P=0.007). CRP levels also correlated significantly with total testosterone levels (r=-0.59; P=0.01). Testosterone treatment reduced leptin (-7141.9 +/- 1461.8 pg/ml; P=0.0001) and adiponectin levels (-2075.8 +/- 852.3 ng/ml; P=0.02). There was a significant reduction in waist circumference. No significant effects of testosterone therapy on resistin, TNF-alpha, IL-6 or CRP levels were observed. CONCLUSION: Testosterone replacement treatment decreases leptin and adiponectin levels in type 2 diabetic men. Moreover, low levels of testosterone in men are associated with pro-inflammatory profile, though testosterone treatment over 3 months had no effect on inflammatory markers.

Behaviours of log phase cultures of eight strains of Escherichia coli incubated at temperatures of 2, 6, 8 and 10 degrees C.

The behaviours of cold-adapted, log-phase cultures of eight strains of Escherichia coli incubated at 2, 6, 8 and 10 degrees C for 10 days were examined by determining absorbance at 600 nm (A(600)), viable counts and cell size distribution as indicated by forward angle light scattering (FALS) values, obtained for samples collected each day from each culture. Cell lengths were determined from photomicrographs of samples for which the flow cytometry data indicated the mean cell lengths were maximal or minimal for each culture. At 2 degrees C, A(600) values for all strains and viable counts for some changed little, while viable counts for other strains declined progressively by >1 log unit. At 6 degrees C, A(600) values for most strains increased at progressively declining rates and then remained constant while viable counts increased to reach maximum values before maximum A(600) values were attained, and then declined. At 8 degrees C, the behaviours of most strains were similar to the behaviour at 6 degrees C. At 10 degrees C, seven of the strains grew exponentially, but for most of these the growth rate determined from A(600) values differed from that determined from viable count data. Mean FALS values for cultures incubated at 6, 8, or 10 degrees C showed various patterns of increase and decrease, indicating fluctuations in cell lengths. For all strains, the minimum cell length was <3 microm, but the maximum cell lengths ranged from <20 to >140 microm. The findings suggest that the formation of elongated cells or filaments is usual behaviour for E. coli growing at temperatures approaching or below the minimum for sustained growth.

Selective inhibition of L-type Ca2+ channels in A7r5 cells by physiological levels of testosterone.

Testosterone has marked beneficial cardiovascular effects, many of which have been attributed to a vasodilatory action. However, the molecular target of testosterone underlying this effect is subject to debate. In this study, we have used microfluorimetry as a noninvasive means of examining whether testosterone could exert dilatory effects via inhibition of voltage-gated Ca2+ entry in the model vascular smooth muscle cell line, A7r5. Rises of [Ca2+]i evoked by 50 mm K+ -containing solution were suppressed in a concentration-dependent manner by testosterone (IC50, 3.1 nm) and by the nonaromatizable analog, 5beta-dihydrotestosterone (IC50, 6.9 nm). The effects of testosterone were apparent in the presence of pimozide (to block T-type Ca2+ channels) but not nifedipine (to block L-type Ca2+ channels). Testosterone did not alter Ca2+ mobilization from intracellular stores by the prostaglandin analog U46619 or capacitative Ca2+ entry in cells pretreated with thapsigargin. Our results indicate that testosterone, at physiological concentrations, can selectively suppress Ca2+ entry into A7r5 cells via L-type Ca2+ channels. We suggest this effect is a likely mechanism underlying its vasodilatory actions and beneficial cardiovascular effects.

Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes.

OBJECTIVE: Low levels of testosterone in men have been shown to be associated with type 2 diabetes, visceral adiposity, dyslipidaemia and metabolic syndrome. We investigated the effect of testosterone treatment on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes. DESIGN: This was a double-blind placebo-controlled crossover study in 24 hypogonadal men (10 treated with insulin) over the age of 30 years with type 2 diabetes. METHODS: Patients were treated with i.m. testosterone 200 mg every 2 weeks or placebo for 3 months in random order, followed by a washout period of 1 month before the alternate treatment phase. The primary outcomes were changes in fasting insulin sensitivity (as measured by homeostatic model index (HOMA) in those not on insulin), fasting blood glucose and glycated haemoglobin. The secondary outcomes were changes in body composition, fasting lipids and blood pressure. Statistical analysis was performed on the delta values, with the treatment effect of placebo compared against the treatment effect of testosterone. RESULTS: Testosterone therapy reduced the HOMA index (-1.73 +/- 0.67, P = 0.02, n = 14), indicating an improved fasting insulin sensitivity. Glycated haemoglobin was also reduced (-0.37 +/- 0.17%, P = 0.03), as was the fasting blood glucose (-1.58 +/- 0.68 mmol/l, P = 0.03). Testosterone treatment resulted in a reduction in visceral adiposity as assessed by waist circumference (-1.63 +/- 0.71 cm, P = 0.03) and waist/hip ratio (-0.03 +/- 0.01, P = 0.01). Total cholesterol decreased with testosterone therapy (-0.4 +/- 0.17 mmol/l, P = 0.03) but no effect on blood pressure was observed. CONCLUSIONS: Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes. Improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk.

Differential expression of proteins in cold-adapted log-phase cultures of Escherichia coli incubated at 8, 6 or 2 degrees C.

Temperature is used to control the growth of microorganisms in foods. The minimum temperature for sustained growth of Escherichia coli is 7 degrees C. E. coli cells in the logarithmic phase of growth at 15 degrees C were incubated at 8, 6 or 2 degrees C. The cells grew with the formation of filaments at the two higher temperatures, but did not grow at 2 degrees C. In order to investigate more thoroughly the nature of filament formation in E. coli at temperatures near the minimum temperature for sustained growth, cells were harvested after 1 day at 2 degrees C or at times up to 4 or 8 days at 8 or 6 degrees C, respectively. Proteins extracted from the cells were separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), and spots containing differentially expressed proteins were identified by quadropole time-of-flight tandem (Q-ToF-2) mass spectrometry. For most of the identified proteins, the amounts were not substantially different in cells grown at 15 degrees C or incubated at 2 degrees C. In cells incubated at 8 or 6 degrees C, proteins associated with stress responses, the tricarboxylic acid cycle and electron transport were present in substantially greater amounts, and proteins associated with protein synthesis were present in substantially smaller amounts than in cells grown at 15 degrees C. These findings suggest that the stringent response is induced in E. coli incubated at temperatures near the minimum for growth, so the formation of filaments at those temperatures may be a result of the stringent response.

Setting control limits for Escherichia coli counts in samples collected routinely from pig or beef carcasses.

Records of Escherichia coli counts in samples routinely collected from carcasses were obtained from one pork and three beef packing plants. The data obtained from each plant were divided into sets from consecutive 6-month periods. For each set of counts, log total counts were calculated for subsets of various sizes. For each set of log total counts, the mean (x), the standard deviation (SD), and an action limit of x + 3 SD were calculated, and the set was tested for a normal distribution. With the data from samples collected at the pork packing plant during 6 years, the proportion of samples with counts of zero in the 12 sets ranged from 15 to 45%. For that plant, appropriate action limits could be derived from log total counts for subsets of nine unit values. With the data from samples collected during 8 years at one beef packing plant, the proportion of samples with counts of zero in the 16 sets ranged from 88 to 99%. For that plant, appropriate action limits could be derived from log total counts for subsets of 15 unit values. With the data from samples collected during 2 or 2.5 years at each of the other beef packing plants, the proportion of samples with counts of zero in all sets was > 99%. For those data, action limits could not be derived from values for subsets of log total counts.

Junior doctors and the full shift rota--psychological and hormonal changes: a comparative cross-sectional study.

We studied the hormonal and psychological effect of the full shift rota on junior doctors after implementation of the European Working Time Directive, using a comparative, cross-sectional study design of male doctors in South Yorkshire. Cortisol and testosterone levels were measured and subjects completed the general health questionnaire (GHQ-12) and the androgen deficiency in the aging male screening questionnaire (ADAM), after a week of holiday (baseline), a week of nights, and a normal working week. The results showed that cortisol levels decreased from 480.6 +/- 33.1 nmol/l at baseline (after a week of holiday), to 355.7 +/- 29.1 nmol/l post normal working week (p = 0.003); to 396.7 +/- 32.5 nmol/l post nights (p = 0.03). GHQ-12 scores increased from 0.5 +/- 0.3 at baseline, to 1.8 +/- 0.5 post normal working week (p = 0.02) and to 2.3 +/- 0.5 post nights (p = 0.005). These results suggest that there are still appreciable physiological consequences with new work patterns.

Revascularization with percutaneous coronary intervention does not affect androgen status in males with chronic stable angina pectoris.

There is a clear association between low serum testosterone and coronary artery disease (CAD) in men. Hypotestosteronaemia is associated with accelerated atherosclerosis and a quarter of men with CAD are biochemically hypogonadal. Amongst those with CAD, hypotestosteronaemia is associated with increased mortality. Testosterone vasodilates coronary arteries, and exogenous testosterone reduces ischaemia. Whether hypotestosteronaemia is a cause or a consequence of CAD remains unanswered. The aim of this prospective observational study was to investigate whether coronary revascularization affected androgen status in men with stable angina pectoris. Twenty five men (mean age 62.7, SD 9.18) with angiographically significant CAD and symptomatic angina underwent full coronary revascularization by percutaneous coronary intervention. Androgen status and symptoms of angina, stress, depression and sexual function were assessed before, and at one and 6 months after the coronary revascularization. All patients underwent complete revascularization which was associated with a significant reduction in angina symptoms and ischaemia. No significant difference was seen in total testosterone (11.33 nmol/L baseline; 12.56, 1 month post; 13.04 at 6 months; p = 0.08). A significant and sustained rise in sex hormone-binding globulin was seen (33.99 nm/L baseline; 36.11 nm/L 1 month post PCI; 37.94 nm/L at 6 months; p = 0.03) Overall, there was no significant alteration in any other marker of androgen status including free testosterone or bioavailable testosterone. There was no change in symptoms of anxiety, depression or sexual function. Coronary revascularization has no sustained effect on androgen status. This supports the hypothesis that hypotestosteronaemia is not a consequence of angina pectoris or myocardial ischaemia.

Bradykinin stimulates the production of prostaglandin E2 and interleukin-6 in human osteoblast-like cells.

The effect of bradykinin (BK) on proteinase activity, prostaglandin synthesis, and the production of interleukin-6 (IL-6) was investigated in cultures of human osteoblast-like cells. Bradykinin had no effect on stromelysin activity and plasminogen activator activity produced by human osteoblast-like cells. However, BK stimulated the production of prostaglandin E2, an effect that was markedly enhanced by pre-incubation with recombinant interleukin-1 alpha (rhIL-1 alpha), but was apparently unaffected by BK receptor antagonists types 1 and 2. Bradykinin stimulated the intracellular accumulation of total inositol phosphates suggesting that its effects were mediated by stimulation of phosphoinositide metabolism. Bradykinin within the dose range of 10(-11)-10(-5) M also significantly stimulated the production of IL-6. Bradykinin may, therefore, mediate a variety of responses in bone under both physiological and pathological conditions.