Impairment of chemoattractant-stimulated hexose uptake in neonatal neutrophils

Neonatal neutrophils (polymorphonuclear leukocytes [PMN]) exhibit a well-documented deficiency in chemotaxis, the nature of which has not been fully elucidated. To determine whether impaired ability of neonatal PMN to increase hexose uptake in response to chemoattractants could contribute to this defect, we compared uptake of 2-deoxy-D- glucose (2-DOG) in stimulated versus resting PMN from neonates (cord blood) and healthy adults. Compared with unstimulated values; N-formyl- methionyl-leucyl-phenylalanine (fMLP) (optimal at 10 nmol/L) caused a threefold to fourfold increase in 2-DOG uptake by adult PMN. Unstimulated 2-DOG uptake by neonatal PMN was slightly higher than that for adult cells, but fMLP caused only a minimal (less than twofold) increase, and optimally stimulated uptake was significantly lower than for adult PMN (P < .01 for adult versus neonatal stimulated uptake; n = 6). Findings were similar when ionomycin or C5a was used as a stimulus. Optimal fMLP stimulation of adult PMN was associated with a marked decrease in the Km for 2-DOG uptake, from 0.74 +/- 0.11 to 0.23 +/- 0.03 mmol/L (delta Km = -0.51 +/- 0.12 mmol/L; n = 6). In contrast, there was relatively little fMLP-induced change in the Km for uptake of 2-DOG by neonatal PMN (from 0.44 +/- 0.04 mmol/L to 0.32 +/- 0.019 mmol/L n = 6); delta Km = -0.12 +/- 0.04 mmol/L; P = .011 for adult versus neonatal delta Km. Stimulation with fMLP was not accompanied by a significant change in the Vmax for 2-DOG uptake with either adult or neonatal PMN, and the respective values for Vmax were similar. We conclude that the chemoattractant-induced increase in hexose uptake by PMN is deficient in neonates compared with adults and that this deficiency involves mechanisms that determine the Km for this process. This impairment may contribute to defective chemotaxis in neonatal PMN.     

Effects of free fatty acids on ACTH and cortisol secretion in anorexia nervosa

OBJECTIVE: Free fatty acids (FFAs) exert a stimulatory effect on the hypothalamic-pituitary-adrenal (HPA) axis in animals and inhibit spontaneous ACTH and cortisol secretion in humans. Patients with anorexia nervosa display concomitant HPA axis hyperactivity and increased lipolysis. We studied the effects of a lipid load on ACTH and cortisol secretion in patients with anorexia nervosa in comparison with normal subjects. DESIGN: Eight women with anorexia nervosa (ANW; means +/- s.e.m.: 23.9 +/- 2.3 years of age; body mass index (BMI): 14.9 +/- 0.6 kg/m2) and seven normal women (NW; 25.6 +/- 2.3 years of age; BMI: 22.8 +/- 1.9 kg/m2) had FFA, ACTH, cortisol, glucose and insulin levels measured in the morning every 30 min for 180 min during i.v. saline or lipid-heparin emulsion (LHE) infusion. RESULTS: During saline infusion, ACTH and cortisol levels decreased spontaneously in both groups, ACTH and cortisol levels in ANW being higher than in NW. LHE infusion led to increased FFA levels in both groups (P < 0.005). The ACTH and cortisol decrease in NW was more marked than during saline infusion (P < 0.05). LHE infusion in ANW was associated with a more pronounced decrease in ACTH levels than during saline infusion (P < 0.05), while cortisol levels were unchanged. At the end of the LHE infusion, a progressive decrease in FFA levels was associated with an increase in ACTH and cortisol concentrations in NW (P < 0.05) but not in ANW in whom FFA levels decreased to a lesser extent (P < 0.05). CONCLUSIONS: This study showed that corticotroph sensitivity to the inhibitory effect of an FFA load is preserved in patients with anorexia nervosa, in spite of persistent adrenal hyperactivity.     

Varicocele sclerotherapy improves serum inhibin B levels and seminal parameters

The usefulness of treating varicocele in order to improve fertility is still a matter of debate. The aim of this study was to evaluate variations in seminal parameters and inhibin B concentrations in a group of males affected by varicocele and treated by percutaneous retrograde sclerotherapy in comparison with a group of patients who did not undergo varicocele treatment. Thirty-eight patients with left varicocele underwent spermatic vein phlebography and percutaneous retrograde sclerotherapy with hydroxy-polyaethoxy-dodecanol. Serum inhibin B, follicle-stimulating hormone (FSH), testosterone levels and seminal parameters (sperm concentration, motility and morphology) were performed before and 6 months after sclerotherapy. Forty patients with left varicocele who did not undergo sclerotherapy were studied as controls. A significant increase (p < 0.01) in serum inhibin B levels and a significant decrease (p < 0.05) in FSH levels were observed 6 months after treatment. Semen analysis showed a significant improvement in sperm concentration (p < 0.05) and progressive motility (p < 0.01) after treatment. In control group no significant variations in hormonal and seminal parameters were observed 6 months after the basal examination. Six months after the basal evaluation, inhibin B levels were significantly higher in treated subjects than in controls (p < 0.05) whereas FSH levels were significantly lower (p < 0.05). Sperm concentration and progressive motility were significantly increased (p < 0.05 and p < 0.001, respectively) in treated subjects in comparison with controls. In conclusion, varicocele sclerotherapy improves inhibin B levels and seminal parameters, confirming the positive effect of this treatment on spermatogenesis and Sertoli cell function.     

Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety

Background and purpose:

Thrombus formation is commonly associated with pulmonary arterial hypertension (PAH). Thrombin may thus play an important role in the pathogenesis and pathophysiology of PAH. Hence, we investigated the contractile effects of thrombin and its mechanism in pulmonary artery.

Experimental approach:

The cytosolic Ca²⁺ concentrations ([Ca²⁺]_i), 20 kDa myosin light chain (MLC20) phosphorylation and tension development were evaluated using the isolated porcine pulmonary artery.

Key results:

Thrombin induced a sustained contraction in endothelium-denuded strips obtained from different sites of a pulmonary artery, ranging from the main pulmonary artery to the intrapulmonary artery. In the presence of endothelium, thrombin induced a transient relaxation. The contractile effect of thrombin was abolished by either a protease inhibitor or a proteinase-activated receptor 1 (PAR₁) antagonist, while it was mimicked by PAR₁-activating peptide (PAR₁AP), but not PAR₄AP. The thrombin-induced contraction was associated with a small elevation of [Ca²⁺]_i and an increase in MLC20 phosphorylation. Thrombin and PAR₁AP induced a greater increase in tension for a given [Ca²⁺]_i elevation than that obtained with high K⁺-depolarization. They also induced a contraction at a fixed Ca²⁺ concentration in α-toxin-permeabilized preparations.

Conclusions and implications:

The present study revealed a unique property of the pulmonary artery. In contrast to normal arteries of the systemic circulation, thrombin induces a sustained contraction in the normal pulmonary artery, by activating PAR₁ and thereby increasing the sensitivity of the myofilament to Ca²⁺. This responsiveness of the pulmonary artery to thrombin may therefore contribute to the pathogenesis and pathophysiology of PAH.     

Recognition of pollen-derived phosphatidyl-ethanolamine by human CD1d-restricted gamma delta T cells

BACKGROUND: Evidences from mice and human beings indicate that gammadelta T cells could be relevant in recognition of stress-induced self and/or yet unidentified inhaled foreign antigens. Their specificity differs from classic MHC-restricted alphabeta T cells and involves the immunoglobulin-like structure of the gammadelta T-cell receptor with the recognition of small organic molecules, alkylamines, and self lipid compounds presented by CD1+ dendritic cells. OBJECTIVE: Because CD1 receptors are mainly devoted to lipid antigen presentation, we sought to determine whether exogenous pollen membrane lipids may act as allergens for CD1-restricted gammadelta T cells. METHODS: Peripheral blood and nasal mucosa-associated gammadelta T cells were cloned from normal controls and cypress-sensitive subjects and tested for their antigen specificity and CD1-restriction with phospholipids extracted from tree pollen grains, as well with other natural or synthetic compounds. Phospholipid reactivity of cloned gammadelta T cells was measured by mean of proliferative response and cytokine release as well as by testing their helper activity on IgE production in vitro and in vivo. RESULTS: Cloned gammadelta T lymphocytes from subjects with allergy, but not normal controls, were found to recognize pollen-derived phosphatidyl-ethanolamine (PE) in a CD1d-restricted fashion. Only 16:0/18:2 and 18:2/18:2 PE were stimulatory, whereas no response was recorded for disaturated PE, phosphatidylcholine, neutral lipids, or protein extract. Proliferating clones secreted both T(H)1-type and T(H)2-type cytokines and drove IgE production in vitro and in vivo. CONCLUSION: CD1d-restricted gammadelta T cells specific for phospholipids can represent a key mucosal regulatory subset for the control of early host reactivity against tree pollens. CLINICAL IMPLICATIONS: By knowing how lipid allergen constituents interact with mucosal immune system, we can expand our possibilities in diagnostic and therapeutic interventions.     

肩周炎20例的综合疗效

1 临床资料 2004-04以来收治肩周炎20(男8,女10)例;年龄42～55岁19例,70岁1例;右侧16例,左侧4例;病史7 d～1.5 a,均无外伤史,患侧肩部活动受限,手臂上提小于40°,肩关节外展,外旋活动受限,不能自如穿、脱衣和梳理头发及摸背. 分型与药物组方见表1.     

Is there any role for thoracoscopy in the diagnosis of benign pleural effusions

Thoracoscopy in the endoscopy suite, has a high diagnostic yield of undiagnosed pleural effusions with minimal and mild complications. Whereas relatively minimal invasive techniques, such as thoracentesis, image‐guided pleural biopsy or blind pleural biopsy, can yield sufficient cell or tissue material to establish the diagnosis of the underlying condition, more definite invasive diagnostic and therapeutic procedure, such as thoracoscopy, may be required for accurate sampling and diagnosis, and further provide real‐time treatment options in same procedure. If thoracoscopy is considered the gold standard for the diagnosis is a fact in case. The current review aims to provide informations on thoracoscopy indications in benign pleural diseases according to up to date publications.     

Family and home correlates of children's physical activity in a multi-ethnic population: the cross-sectional child heart and health study in england (CHASE)

Background  

The influence of the family and home environment on childhood physical activity (PA) and whether this differs between ethnic groups remains uncertain. This paper investigates associations between family and home factors and childhood PA in a multi-ethnic population and explores whether associations differ between ethnic groups.     

A Lower Sodium Neapolitan Pizza Prepared with Seawater in Place of Salt: Nutritional Properties,Sensory Characteristics,and Metabolic Effects

Seawater is rich in minerals which may help confer good palatability to foods, favouring the use of smaller amounts of salt, a recognized measure of cardiovascular prevention. The aim of this study was to investigate the nutritional properties, sensory characteristics and metabolic effects of a typical Neapolitan pizza prepared with seawater (SWP) in place of common salt, in comparison with Standard traditional Pizza (StP). The nutritional characteristics and the chemical profile of the SWP and StP were assessed by chemical analyses and the use of Food Composition Tables. Twelve healthy volunteers were recruited for a Randomized Controlled Trial, with the consumption of one StP and one SWP using a balanced crossover design. The satiating power and palatability of the two pizzas were tested by the administration of Visual Analogue Scales. Serum glucose, insulin and sodium were measured every 30 min and 3 h urines were collected after each meal. SWP contained nearly 50% less NaCl and a larger amount of micronutrients compared with StP. No significant differences were detected between the two pizzas with regard to satiating power, pleasantness and glycemic and insulinemic response. However, a significant difference was found in the urine volume collected over the 3 h after the two meals (194 mL after StP vs. 292 mL after SWP, p = 0.018) and in the 3 h sodium balance (+1.6 g after StP vs. +0.5 g after SWP, p = 0.002). Conclusions: SWP appears to be a food with favourable nutritional characteristics, very good acceptability and healthy metabolic properties: these results warrant confirmation by a larger intervention trial.     

Parallel synthesis and cytotoxicity evaluation of a polyamine-quinone conjugates library

A library of 24 derivatives designed by combining two natural products-derived fragments was prepared and tested to determine their anticancer potential in HT29 colon cancer cells. All library members inhibit cell proliferation as measured by MTT mitochondrial functional assay, with IC50 values in the 1-100 microM range. Entry 1b caused apoptotic EGFR-mediated intracellular signaling. Thus, polyamino-quinones emerged as readily accessible and easily diversified scaffolds for anticancer lead discovery.