Insulin and GH Signaling in Human Skeletal Muscle In Vivo following Exogenous GH Exposure: Impact of an Oral Glucose Load

GH induces acute insulin resistance in skeletal muscle in vivo, which in rodent models has been attributed to crosstalk between GH and insulin signaling pathways. Our objective was to characterize time course changes in signaling pathways for GH and insulin in human skeletal muscle in vivo following GH exposure in the presence and absence of an oral glucose load.Eight young men were studied in a single-blinded randomized crossover design on 3 occasions: 1) after an intravenous GH bolus 2) after an intravenous GH bolus plus an oral glucose load (OGTT), and 3) after intravenous saline plus OGTT. Muscle biopsies were taken at t = 0, 30, 60, and 120. Blood was sampled at frequent intervals for assessment of GH, insulin, glucose, and free fatty acids (FFA).GH increased AUC(glucose) after an OGTT (p<0.05) without significant changes in serum insulin levels. GH induced phosphorylation of STAT5 independently of the OGTT. Conversely, the OGTT induced acute phosphorylation of the insulin signaling proteins Akt (ser(473) and thr(308)), and AS160.The combination of OGTT and GH suppressed Akt activation, whereas the downstream expression of AS160 was amplified by GH. WE CONCLUDED THE FOLLOWING: 1) A physiological GH bolus activates STAT5 signaling pathways in skeletal muscle irrespective of ambient glucose and insulin levels 2) Insulin resistance induced by GH occurs without a distinct suppression of insulin signaling proteins 3) The accentuation of the glucose-stimulated activation of AS 160 by GH does however indicate a potential crosstalk between insulin and GH.ClinicalTrials.gov NCT00477997

Can We Really Prevent Suicide?

Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia

The Hordaland Women's Cohort: A prospective cohort study of incontinence, other urinary tract symptoms and related health issues in middle-aged women

<p>Abstract</p> <p>Background</p> <p>Urinary incontinence (UI) is a prevalent symptom in middle-aged women, but data on incidence is limited and rarely reported. In order to analyze incidence, remission, or development patterns of severity and types of UI, we have established a 15-year prospective cohort (1997–2012).</p> <p>Methods</p> <p>The Cohort is based on the national collection of health data gathered from county studies (CONOR). Hordaland Health Study (HUSK) is one of them from Hordaland County. Each of the county studies may have local sub-studies and our Cohort is one of them. The Cohort included women aged 40–45 in order to have a broad approach to women's health including UI and other lower urinary tract symptoms (LUTS). A onefifth random sampling from HUSK was used to create the Cohort in 1997–1999. For the necessary sample size a preliminary power calculation, based on a 70% response rate at inclusion and 5% annual attrition rates was used. The Cohort is planned to collect data through questionnaires every second year for the 15-year period from 1997–2012.</p> <p>Discussion</p> <p>The Cohort represents a relatively large random sample (N = 2,230) of about 15% of the total population of women born between 1953–57 in the county of Hordaland. Our data shows that the cohort population is very similar to the source population. The baseline demographic, social and medical characteristics of the Cohort are compared with the rest of women in HUSK (N = 7,746) and there were no significant differences between them except for the level of education (P = 0.001) and yearly income (P = 0.018), which were higher in the Cohort population. Urological characteristics of participants from the Cohort (N = 1,920) were also compared with the other participants (N = 3,400). There were no significant statistical differences except for somewhat more urinary continence (P = 0.04), more stress incontinence (P = 0.048) and smaller amount of leakage (P = 0.015) in the Cohort. In conclusion, the Cohort ispopulation-based, with little selection bias, and thus is a rather unique study forinvestigating UI and LUTS in comparison with many other projects with similar purposes.</p

Prevalence of urinary incontinence in Andorra: impact on women's health.

BACKGROUND: Urinary incontinence (UI) is a frequent public health problem with negative social consequences, particularly for women. Female susceptibility is the result of anatomical, social, economic and cultural factors. The main objectives of this study are to evaluate the prevalence of UI in the female population of Andorra over the age of 15 and, specifically, to determine the influence of socio-demographic factors. A secondary aim of the study is to measure the degree of concern associated with UI and whether the involved subjects have asked for medical assistance, or not. METHODS: Women aged 15 and over, answered a self-administered questionnaire while attending professional health units in Andorra during the period November 1998 to January 2000. A preliminary study was carried out to ensure that the questionnaire was both understandable and simple. RESULTS: 863 completed questionnaires were obtained during a one year period. The breakdown of the places where the questionnaires were obtained and filled out is as follows: 32.4% – medical specialists' offices; 31.5% – outpatient centres served exclusively by nurses; 24% – primary care doctors' offices; 12% from other sources. Of the women who answered the questionnaire, 37% manifested urine losses. Of those,45.3% presented regular urinary incontinence (RUI) and 55.7% presented sporadic urinary incontinence (SporadicUI). In those women aged between 45 and 64, UI was present in 56% of the subjects. UI was more frequent among parous than non-parous women. UI was perceived as a far more bothersome and disabling condition by working, middle-class women than in other socio-economic groups. Women in this particular group are more limited by UI, less likely to seek medical advice but more likely to follow a course of treatment. From a general point of view, however, less than 50% of women suffering from UI sought medical advice. CONCLUSION: The prevalence of UI in the female population of Andorra stands at about 37%, a statistic which should encourage both health professionals and women to a far greater awareness of this condition

Use of selective serotonin reuptake inhibitors and risk of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Selective serotonin reuptake inhibitors (SSRI) decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association.</p> <p>Methods</p> <p>We conducted a population-based study of the risk of re-operation due to post-surgical bleeding within two weeks of primary surgery among Danish women with primary breast cancer. Patients were categorised according to their use of SSRI: never users, current users (SSRI prescription within 30 days of initial breast cancer surgery), and former users (SSRI prescription more than 30 days before initial breast cancer surgery). We calculated the risk of re-operation due to post-surgical bleeding within 14 days of initial surgery, and the relative risk (RR) of re-operation comparing SSRI users with never users of SSRI adjusting for potential confounders.</p> <p>Results</p> <p>389 of 14,464 women (2.7%) were re-operated. 1592 (11%) had a history of SSRI use. Risk of re-operation was 2.6% among never users, 7.0% among current SSRI users, and 2.7% among former users. Current users thus had an increased risk of re-operation due to post-operative bleeding (adjusted relative risk = 2.3; 95% confidence interval (CI) = 1.4, 3.9) compared with never users. There was no increased risk of re-operation associated with former use of SSRI (RR = 0.93, 95% CI = 0.66, 1.3).</p> <p>Conclusions</p> <p>Current use of SSRI is associated with an increased risk of re-operation due to bleeding after surgery for breast cancer.</p

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

Respiration-averaged CT versus standard CT attenuation maps for correction of the 18F-NaF uptake in hybrid PET/CT

BACKGROUND: To evaluate the impact of respiratory-averaged computed tomography attenuation correction (RACTAC) compared to standard single-phase computed tomography attenuation correction (CTAC) map, on the quantitative measures of coronary atherosclerotic lesions of (18)F-sodium fluoride ((18)F-NaF) uptake in hybrid positron emission tomography and computed tomography (PET/CT). METHODS: This study comprised 23 patients who underwent (18)F-NaF coronary PET in a hybrid PET/CT system. All patients had a standard single-phase CTAC obtained during free-breathing and a 4D cine-CT scan. From the cine-CT acquisition, RACTAC maps were obtained by averaging all images acquired over 5 seconds. PET reconstructions using either CTAC or RACTAC were compared. The quantitative impact of employing RACTAC was assessed using maximum target-to-background (TBR(MAX)) and coronary microcalcification activity (CMA). Statistical differences were analyzed using reproducibility coefficients and Bland-Altman plots. RESULTS: In 23 patients, we evaluated 34 coronary lesions using CTAC and RACTAC reconstructions. There was good agreement between CTAC and RACTAC for TBR(MAX) (median [Interquartile range]): CTAC= 1.65[1.23–2.38], RACTAC= 1.63[1.23–2.33], p=0.55), with coefficient of reproducibility of 0.18, and CMA: CTAC= 0.10 [0–1.0], RACTAC= 0.15[0–1.03], p=0.55 with coefficient of reproducibility of 0.17 CONCLUSION: Respiratory-averaged and standard single-phase attenuation correction maps provide similar and reproducible methods of quantifying coronary (18)F-NaF uptake on PET/CT

Intradialytic versus home based exercise training in hemodialysis patients: a randomised controlled trial

Background: Exercise training in hemodialysis patients improves fitness, physical function, quality of life and markers of cardiovascular disease such as arterial stiffness. The majority of trials investigating this area have used supervised exercise training during dialysis (intradialytic), which may not be feasible for some renal units. The aim of this trial is to compare the effects of supervised intradialytic with unsupervised home-based exercise training on physical function and arterial stiffness

Antioxidant rich flavonoids from Oreocnide integrifolia enhance glucose uptake and insulin secretion and protects pancreatic β-cells from streptozotocin insult

<p>Abstract</p> <p>Background</p> <p>Insulin deficiency is the prime basis of all diabetic manifestations and agents that can bring about insulin secretion would be of pivotal significance for cure of diabetes. To test this hypothesis, we carried out bioactivity guided fractionation of <it>Oreocnide integrifolia </it>(Urticaceae); a folklore plant consumed for ameliorating diabetic symptoms using experimental models.</p> <p>Methods</p> <p>We carried out bioassay guided fractionation using RINmF and C2C12 cell line for glucose stimulated insulin secretion (GSIS) and glucose uptake potential of fractions. Further, the bioactive fraction was challenged for its GSIS in cultured mouse islets with basal (4.5 mM) and stimulated (16.7 mM) levels of glucose concentrations. The Flavonoid rich fraction (FRF) was exposed to 2 mM streptozotocin stress and the anti-ROS/RNS potential was evaluated. Additionally, the bioactive fraction was assessed for its antidiabetic and anti-apoptotic property <it>in-vivo </it>using multidose streptozotocin induced diabetes in BALB/c mice.</p> <p>Results</p> <p>The results suggested FRF to be the most active fraction as assessed by GSIS in RINm5F cells and its ability for glucose uptake in C2C12 cells. FRF displayed significant potential in terms of increasing intracellular calcium and cAMP levels even in presence of a phosphodiesterase inhibitor, IBMX in cultured pancreatic islets. FRF depicted a dose-dependent reversal of all the cytotoxic manifestations except peroxynitrite and NO formation when subjected <it>in-vitro </it>along with STZ. Further scrutinization of FRF for its <it>in-vivo </it>antidiabetic property demonstrated improved glycemic indices and decreased pancreatic β-cell apoptosis.</p> <p>Conclusions</p> <p>Overall, the flavonoid mixture has shown to have significant insulin secretogogue, insulinomimetic and cytoprotective effects and can be evaluated for clinical trials as a therapeutant in the management of diabetic manifestations.</p