B‐type natriuretic peptide and C‐terminal‐pro‐endothelin‐1 for the prediction of severely impaired peak oxygen consumption

Objective. To assess the utility of B‐type natriuretic peptide (BNP) and C‐terminal‐pro‐endothelin‐1 (CT‐proET‐1) to predict a severely impaired peak oxygen consumption (peak VO₂, < 14 mL kg^?1 min^?1) in patients referred for cardiopulmonary exercise testing. Design. Cross‐sectional study. Setting. Tertiary care center. Methods. Peak VO₂, BNP and CT‐proET‐1 were assessed in 141 consecutive patients referred for cardiopulmonary exercise testing. Results. B‐type natriuretic peptide [median (interquartile range) 48 (38–319) vs. 33 (15–86) pg mL^?1; P = 0.002] and CT‐proET‐1 [87 (76–95) vs. 60 (52–74) pmol L^?1; P < 0.001] were higher in patients with a peak VO₂ < 14 mL kg^?1 min^?1 (n = 30) than in those with a peak VO₂ ≥ 14 mL kg^?1 min^?1 (n = 111). CT‐pro‐ET‐1 had a higher area under the receiver‐operator‐characteristics curve (AUC) to predict a peak VO₂ < 14 mL kg^?1 min^?1 than BNP (0.79 vs. 0.68; P = 0.04). The optimal BNP cut‐off of 37.2 pg mL^?1 had a sensitivity of 80% and a specificity of 56%. The optimal CT‐proET‐1 cut‐off of 74.4 pmol L^?1 had a sensitivity of 80% and specificity of 76%. A five‐item score composed of body mass index, diabetes, forced expiratory volume within the first second, alveolo–arterial oxygen pressure difference, and BNP had an AUC of 0.88 to predict a peak VO₂ < 14 mL kg^?1 min^?1. Adding CT‐proET‐1 to the score resulted in an AUC of 0.92. Conclusions. C‐terminal‐pro‐endothelin‐1 is superior to BNP for the prediction of a peak VO₂ < 14 mL kg^?1 min^?1 in patients referred for CPET. A score incorporating body mass index, diabetes status, spirometry, blood gases, BNP and CT‐proET‐1 improves the prediction of a peak VO₂ < 14 mL kg^?1 min^?1 based on single biomarkers.     

A comparison of the MMSE and the TICS‐m in hearing‐impaired older adults

Objective: The efficacy of telephone‐administered cognitive screening instruments used with hearing‐impaired populations is as yet unknown. Method: In a pilot study, performance of hearing‐impaired veterans (N = 46) was compared on telephone‐administered (Telephone Interview for Cognitive Status – modified; TICS‐m) and face‐to‐face administered (Mini‐Mental State Examination; MMSE) instruments. Results: Correlations between the MMSE and the TICS‐m (r = 0.39) are lower than previously reported in the literature. Participants had difficulty perceiving words from the TICS‐m on registration and thus also on later recall, regardless of whether hearing aids were worn. Further analyses revealed that when these items were removed from the TICS‐m scores, correlations with the MMSE improved significantly. Conclusions: Hearing‐impaired participants may have difficulties with telephone‐administered instruments requiring accurate hearing of words in the absence of any context. Participants’ hearing should be taken into account when administering and interpreting cognitive screens over the telephone.     

Synaptic dysfunction in human immunodeficiency virus type‐1‐positive subjects: inflammation or impaired neuronal plasticity?

Many people infected with the human immunodeficiency virus type‐1 (HIV) exhibit mild or severe neurological problems, termed HIV‐associated neurocognitive disorder (HAND), even when receiving antiretroviral therapy. Thus, novel adjunctive therapies must be developed to overcome the neurotoxic effect of HIV. New therapies require a better understanding of the molecular and cellular mechanisms of HIV‐induced neurotoxicity and the risk factors that, besides inflammation and T‐cell depletion and drugs of abuse, render the central nervous system (CNS) a target of HIV‐induced neurotoxicity. HIV appears to impair neuronal plasticity, which refers to the innate ability of the CNS respond to injury and promote recovery of function. The availability of brain‐derived neurotrophic factor (BDNF), a potent neurotrophic factor that is present in abundance in the adult brain, is essential for neuronal plasticity. BDNF acts through a receptor system composed of Trk and p75NTR. Here, we present experimental evidence that some of the clinical features of HIV‐mediated neurological impairment could result from altered BDNF/TrkB/p75NTR regulation and function.     

Ingestion of a moderate high‐sucrose diet results in glucose intolerance with reduced liver glucokinase activity and impaired glucagon‐like peptide‐1 secretion

Aims/Introduction: Excessive intake of sucrose can cause severe health issues, such as diabetes mellitus. In animal studies, consumption of a high‐sucrose diet (SUC) has been shown to cause obesity, insulin resistance and glucose intolerance. However, several in vivo experiments have been carried out using diets with much higher sucrose contents (50–70% of the total calories) than are typically ingested by humans. In the present study, we examined the effects of a moderate SUC on glucose metabolism and the underlying mechanism. Materials and Methods: C57BL/6J mice received a SUC (38.5% sucrose), a high‐starch diet (ST) or a control diet for 5 weeks. We assessed glucose tolerance, incretin secretion and liver glucose metabolism. Results: An oral glucose tolerance test (OGTT) showed that plasma glucose levels in the early phase were significantly higher in SUC‐fed mice than in ST‐fed or control mice, with no change in plasma insulin levels at any stage. SUC‐fed mice showed a significant improvement in insulin sensitivity. Glucagon‐like peptide‐1 (GLP‐1) secretion 15 min after oral glucose administration was significantly lower in SUC‐fed mice than in ST‐fed or control mice. Hepatic glucokinase (GCK) activity was significantly reduced in SUC‐fed mice. During the OGTT, the accumulation of glycogen in the liver was suppressed in SUC‐fed mice in a time‐dependent manner. Conclusions: These results indicate that mice that consume a moderate SUC show glucose intolerance with a reduction in hepatic GCK activity and impairment in GLP‐1 secretion. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00208.x , 2012)     

Loss of JAM‐C leads to impaired esophageal innervations and megaesophagus in mice

Megaesophagus is a disease where peristalsis fails to occur properly and esophagus is enlarged. The etiology and mechanism of megaesophagus are not well understood. In this study, we reported that junctional adhesion molecule C (JAM‐C) knockout mice on a C57/B6 background developed progressive megaesophagus from embryonic day (E) 15.5 onward with complete penetrance. JAM‐C knockout mice exhibited a significant reduction in the number of nerve fibers/ganglia in the wall of the esophagus. However, histological analysis revealed that the esophageal wall thickness and structure of JAM‐C knockout mice at embryonic stages and young adult were comparable to that of control littermates. Thus, megaesophagus observed in JAM‐C knockout mice could be attributed, at least in part, to impaired esophageal innervations. Our data suggest JAM‐C as a potential candidate gene for human megaesophagus, and JAM‐C knockout mice might serve as a model for the study of human megaesophagus.     

Differences in insulin resistance and pancreatic B‐cell function in obese subjects with isolated impaired glucose tolerance and isolated impaired fasting glucose

Aims To investigate changes in insulin action and insulin secretion in obese subjects with different categories of impaired glucose regulation (IGR): impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG/IGT (CGI). Methods A total of 222 subjects underwent an oral glucose tolerance test and a frequently sampled intravenous glucose tolerance test (FSIGTT); 100 had normal glucose tolerance (subdivided into 32 lean NGT, 68 obese NGT), and 122 were obese with IGR (82 IGT, 14 IFG and 26 CGI). The insulin sensitivity index (S_I) was assessed by Bergman's minimal model method with FSIGTT; insulin secretion was determined by acute insulin response to glucose (AIRg). The disposition index (DI), the product of AIRg and S_I, was used to determine whether AIRg was adequate to compensate for insulin resistance. Results S_I was similar in NGT and IGR obese subgroups. AIRg was significantly increased in obese NGT as compared with lean NGT, significantly reduced in IGT, and further reduced in IFG and CGI subjects as compared with obese NGT subgroups. DI was reduced in NGT obese individuals. Within the obese IGR subgroups, IFG and CGI subjects had even lower DI value than IGT subjects. Conclusions Obese Chinese subjects with IGR have a similar degree of insulin resistance but differ in insulin secretion. Subjects with IFG and CGI have a more prominent deficiency in insulin secretion than subjects with IGT.