Leptin in human physiology and pathophysiology

Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIV-related lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical applications of leptin or its analogs in human therapeutics.     

Nonparametric Bayesian estimation of the three-way receiver operating characteristic surface

We describe a nonparametric Bayesian approach for estimating the three-way ROC surface based on mixtures of finite Polya trees (MFPT) priors. Mixtures of finite Polya trees are robust models that can handle nonstandard features in the data. We address the difficulties in modeling continuous diagnostic data with skewness, multimodality, or other nonstandard features, and how parametric approaches can lead to misleading results in such cases. Robust, data-driven inference for the ROC surface and for the volume under the ROC surface is obtained. A simulation study is performed to assess the performance of the proposed method. Methods are applied to data from a magnetic resonance spectroscopy study on human immunodeficiency virus patients.     

Effects of polycythemia on systemic endothelial function in chronic hypoxic lung disease

Chronic obstructive pulmonary disease (COPD) is a major risk factor for cardiovascular disease. Polycythemia, a common complication of hypoxic COPD, may affect systemic vascular function by altering blood viscosity, vessel wall shear stress (WSS), and endothelium-derived nitric oxide (NO) release. Here, we evaluated the effects of hypoxia-related polycythemia on systemic endothelial function in patients with COPD. We investigated blood viscosity, WSS, and endothelial function in 15 polycythemic and 13 normocythemic patients with COPD of equal severity, by recording brachial artery diameter variations in response to hyperemia and by using venous occlusion plethysmography (VOP) to measure forearm blood flow (FBF) responses to a brachial artery infusion of acetylcholine (ACh), bradykinin (BK), sodium nitroprusside (SNP), substance P (SP), isoptin, and N-monomethyl-L-arginine (L-NMMA). At baseline, polycythemic patients had higher blood viscosity and larger brachial artery diameter than normocythemic patients but similar calculated WSS. Flow-mediated brachial artery vasodilation was increased in the polycythemic patients, in proportion to the hemoglobin levels. ACh-induced vasodilation was markedly impaired in the polycythemic patients and negatively correlated with hemoglobin levels. FBF responses to endothelium- (BK, SP) and non-endothelium-dependent (SNP, isoptin) vasodilators were not significantly different between the two groups. L-NMMA infusion induced a similar vasoconstrictor response in both groups, in accordance with their similar baseline WSS. In conclusion, systemic arteries in polycythemic patients adjust appropriately to chronic or acute WSS elevations by appropriate basal and stimulated NO release. Overall, our results suggest that moderate polycythemia has no adverse effect on vascular function in COPD.     

Critical role for a stage-specific actin in male exflagellation of the malaria parasite

Male gametogenesis occurs directly after uptake of malaria parasites by the mosquito vector and leads to the release of eight nucleated flagellar gametes. Here, we report that one of the two parasite actin isoforms, named actin II, is essential for this process. Disruption of actin II in Plasmodium berghei resulted in viable asexual blood stages, but male gametogenesis was specifically inhibited. Upon activation, male gametocyte DNA was replicated normally and axonemes assembled, but egress from the host cell was inhibited, and axoneme motility abolished. The major actin isoform, actin I, displayed dual localization to the cytoplasm and the nucleus in male gametocytes. After activation actin I was found to be restricted to the cytoplasm. In actII(-) mutant parasites, this re-localization was abolished and actin I remained in both cellular compartments. These findings reveal vital and pleiotropic functions for the actin II isoform in male gametogenesis of the malaria parasite.     

Kinetic and training comparisons between assisted, resisted, and free countermovement jumps

Elastic band assisted and resisted jump training may be a novel way to develop lower-body power. The purpose of this investigation was to (a) determine the kinetic differences between assisted, free, and resisted countermovement jumps and (b), investigate the effects of contrast training using either assisted, free, or resisted countermovement jump training on vertical jump performance in well-trained athletes. In part 1, 8 recreationally trained men were assessed for force output, relative peak power (PP·kg(-1)) and peak velocity during the 3 types of jump. The highest peak force was achieved in the resisted jump method, while PP·kg(-1) and peak velocity were greatest in the assisted jump. Each type of jump produced a different pattern of maximal values of the variables measured, which may have implications for developing separate components of muscular power. In part 2, 28 professional rugby players were assessed for vertical jump height before and after 4 weeks of either assisted (n = 9), resisted (n = 11), or free (n = 8) countermovement jump training. Relative to changes in the control group (1.3 ± 9.2%, mean ± SD), there were clear small improvements in jump height in the assisted (6.7 ± 9.6%) and the resisted jump training group (4.0 ± 8.8%). Elastic band assisted and resisted jump training are both effective methods for improving jump height and can be easily implemented into current training programs via contrast training methods or as a part of plyometric training sessions. Assisted and resisted jump training is recommended for athletes in whom explosive lower-body movements such as jumping and sprinting are performed as part of competition.     

Effect of three MAP compositions on the physical and microbiological properties of a low fat Greek cheese known as "Anthotyros"

Anthotyros is a type of low fat cheese produced from a mixture of sheep and goat milk. Anthotyros cheese in Crete is produced from the whey of hard cheese such as kefalotyri and graviera. Anthotyros is a cheese which comes from the myzithra cheese (whey) dehydration. The dehydrated anthotyros’ physicochemical properties are moisture content of 35%, fat content in dry matter of 55% and low concentration of salt. The purpose of this study was to identify which of the three gas compositions applied; MAP₁:40% CO₂, 55% N₂, 5% O₂, MAP₂: 60% CO₂, 40% N₂ and MAP₃: 50% CO₂, 50% N₂ can lead to greater shelf life prolongation of anthotyros. The control samples were packaged in air. All cheese samples were kept under refrigeration (4 ± 0.5 °C) for 55 days. The statistical analysis of organoleptic characteristics was carried out by using the Principal Component Analysis (PCA) by means of JMP5.0.1.     

Effect of several MAP compositions on the microbiological and sensory properties of Graviera cheese

The shelf life of Graviera cheese, a full fat cheese produced in Heraklion (Crete Greece), was investigated. Graviera cheese was stored at 4 °C for up to 90 days in polyamide packages under three different modified atmosphere compositions. Control cheeses were packaged in air whereas MAP mixtures were MAP₁: 40% CO₂/55% N₂/5% O₂, MAP₂: 60% CO₂/40% N₂ and MAP₃: 50% CO₂/50% N₂. Sampling of product was carried out every 10 days to investigate its sensory quality and microbiological characteristics. Ten trained panelists participated in the sensory panel to evaluate the cheeses for external appearance (color, texture), taste, and flavor in a scale from 1 to 10 (1 very poor, 10 very good). The microbiological analysis revealed that there were no colonies of Staphylococcus aureus and Listeria monocytogenes whereas both Escherichia coli and Total Viable Counts (TVC) increased strongly in control samples but were inhibited under all MAP compositions.