Insulin resistance and sex hormone‐binding globulin are independently correlated with low free testosterone levels in obese males

Male obesity is associated with decreased testosterone levels but the pathophysiological mechanisms behind this association are not completely understood. This study aimed to investigate the impact of hyperglycaemia/insulin resistance and sex hormone‐binding globulin (SHBG) levels on testosterone levels in a population of obese men. We investigated the impact of several clinical, anthropometric and analytic measures on testosterone levels in 150 obese males. Testosterone deficiency was present in 52.0% of the enrolled patients. This percentage dropped to 17.6% when only calculated free testosterone (FT) was accounted, as SHBG levels were correlated negatively with body mass index (r = ?.20; p < .05). Older age (p < .05) and higher homoeostasis model assessment of insulin resistance (HOMA‐IR) (p < .01) and lower SHBG levels (p < .05) were independently correlated with lower FT. Weight and fasting plasma glucose lost their statistical significance after multivariate adjustment. Patients with type 2 diabetes mellitus and pre‐diabetes had lower FT than those with normal glucose tolerance (p < .05 and p < .01 respectively). Insulin resistance, and not hyperglycaemia and weight per se, seems to be the main determinant of low testosterone levels in obese males. Low SHBG levels are correlated with low FT even after HOMA‐IR adjustment. This suggests that SHBG can be associated with testosterone deficiency beyond the influence of insulin resistance unlike previously reported.     

Application of CRISPR-Cas9-Mediated Genome Editing for the Treatment of Myotonic Dystrophy Type 1

1. Download : Download high-res image (143KB)
2. Download : Download full-size image

     

Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients

Oxidative stress is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In the present study, hepatic and plasma oxidative stress-related parameters were measured and correlated with clinical and histological findings in 31 NAFLD patients showing increased body mass index. Liver protein carbonyl content was enhanced by 403% in patients with steatosis (n=15) compared with control values (n=12), whereas glutathione content, superoxide dismutase (SOD) activity and the ferric reducing ability of plasma (FRAP) were decreased by 57%, 48% and 21% (P<0.05) respectively. No changes in microsomal p-nitrophenol hydroxylation and the total content of cytochrome P450 (CYP) or CYP2E1 were observed. Patients with steatohepatitis (n=16) exhibited protein carbonyl content comparable with that of controls, whereas glutathione content, SOD and catalase activities were decreased by 27%, 64% and 48% (P<0.05). In addition, FRAP values in patients with steatohepatitis were reduced by 33% and 15% (P<0.05) when compared with controls and patients with steatosis respectively, whereas p-nitrophenol hydroxylation (52%) and CYP2E1 content (142%) were significantly increased (P<0.05) compared with controls. It is concluded that oxidative stress is developed in the liver of NAFLD patients with steatosis and is exacerbated further in patients with steatohepatitis, which is associated with CYP2E1 induction. Substantial protein oxidation is followed by proteolysis of the modified proteins, which may explain the co-existence of a diminished antioxidant capacity and protein oxidation in the liver of patients with steatohepatitis.     

Translating probiotic science into practice

Scientific and clinical evidence on the health effects of probiotics has expanded rapidly in recent years and points towards benefits for a number of specific health conditions, particularly those related to the gut. Healthcare professionals are important conduits in the transfer of evidence‐based messages on probiotics, but research indicates many do not consider themselves to have good knowledge in this area. To identify potential solutions to support healthcare professionals, the British Nutrition Foundation held a one‐day roundtable event on 7 February 2019 to gather expert views on the content of, and best delivery mode for, evidence‐based resources to guide healthcare professional advice about the use of probiotics. This report describes the main themes emerging from the discussions and the group's recommendation for the development of a UK‐focused online toolkit for healthcare professionals, which assimilates, appraises and translates current scientific knowledge of probiotics to promote evidence‐based practice for the benefit of patients.     

Influence of Ghrelin and Growth Hormone Deficiency on AMP‐Activated Protein Kinase and Hypothalamic Lipid Metabolism

Current evidence demonstrates that the stomach‐derived hormone ghrelin, a potent growth hormone (GH) secretagogue, promotes feeding through a mechanism involving the short‐term activation of hypothalamic AMP‐activated protein kinase (AMPK), which in turn results in decreased hypothalamic levels of malonyl‐CoA and increased carnitine palmitoyltransferase 1 (CPT1) activity. Despite this evidence, no data have been reported about the effect of chronic, central ghrelin administration on hypothalamic fatty acid metabolism. In the present study, we examined the differences in hypothalamic fatty acid metabolism in the presence and absence of GH, by using a model for the study of GH‐deficiency, namely the spontaneous dwarf rat and the effect of long‐term central ghrelin treatment and starvation on hypothalamic fatty acid metabolism in this animal model. Our data showed that GH‐deficiency induces reductions in both de novo lipogenesis and β‐oxidation pathways in the hypothalamus. Thus, dwarf rats display reductions in fatty acid synthase (FAS) mRNA expression both in the ventromedial nucleus of the hypothalamus (VMH) and whole hypothalamus, as well as in FAS protein and activity. CPT1 activity was also reduced. In addition, in the present study, we show that chronic ghrelin treatment does not promote AMPK‐induced changes in the overall fluxes of hypothalamic fatty acid metabolism in normal rats and that this effect is independent of GH status. By contrast, we demonstrated that both chronic ghrelin and fasting decreased FAS mRNA expression in the VMH of normal rats but not dwarf rats, suggesting GH status dependency. Overall, these results suggest that ghrelin plays a dual time‐dependent role in modulating hypothalamic lipid metabolism. Understanding the molecular mechanism underlying the interplay between GH and ghrelin on hypothalamic lipid metabolism will allow new strategies for the design and development of suitable drugs for the treatment of GH‐deficiency, obesity and its comorbidities.     

抑制磷酸二酯酶5治疗心力衰竭的机制和临床意义

磷酸二酯酶5（PDE5）影响环磷酸鸟苷（cGMP）维持血管平滑肌紧张性的生理学效应,在阴茎海绵体的静脉系统和肺血管系统中尤为明显。     

Bipolar scissors circumcision is a safe, fast, and bloodless procedure in children

Purpose

The aim of this study is to evaluate bipolar scissors circumcision by comparing it with standard freehand scalpel procedure.

Patients and Methods

Data were analyzed from a prospective, randomized study, comparing 2 different surgical techniques for pediatric circumcision: the bipolar diathermy scissors circumcision technique with those of a conventional scalpel technique. A total of 230 pediatric patients younger than 16 years (115 in each arm of the trial) who were undergoing circumcision were reviewed prospectively. Operative time, surgical bleeding, complications, and postoperative morbidity were analyzed. Differences between bipolar scissors circumcision and conventional surgery were compared.

Results

Median blood loss for bipolar circumcision was 0.2 mL (range, 0-0.8 mL) compared with 2.1 mL in the standard group (range, 0.9-4.2 mL) (P < .001). Operative time in the bipolar diathermy treated group was significantly decreased compared with conventionally treated patients (10.8 ± 1.2 vs 19.1 ± 2.6 minutes; P < .01). Early and late postoperative morbidity were significantly decreased in circumcised patients who underwent the bipolar circumcision technique as compared with those who underwent the conventional approach regardless of the postoperative edema (22 vs 10; P = .02).

Conclusions

Bipolar scissors circumcision approach is an effective and safe procedure alternative to the standard scalpel technique in pediatric circumcision with no significant morbidity.