Human sperm pattern of movement during chemotactic ＇e-orientation towards a progesterone source

Human spermatozoa may chemotactically find out the egg by following an increasing gradient of attractant molecules. Although human spermatozoa have been observed to show several of the physiological characteristics of chemotaxis, the chemotactic pattern of movement has not been easy to describe. However, it is apparent that chemotactic cells may be identified while returning to the attractant source. This study characterizes the pattern of movement of human spermatozoa during chemotactic re-orientation towards a progesterone source, which is a physiological attractant candidate. By means of videomicroscopy and image analysis, a chemotactic pattern of movement was identified as the spermatozoon returned towards the source of a chemotactic concentration of progesterone (10 pmol l⁻¹). First, as a continuation of its original path, the spermatozoon swims away from the progesterone source with linear movement and then turns back with a transitional movement that can be characterized by an increased velocity and decreased linearity. This sperm behaviour may help the spermatozoon to re-orient itself towards a progesterone source and may be used to identify the few cells that are undergoing chemotaxis at a given time.     

Effect of erythromycin on gallbladder emptying in diabetic patients with and without autonomic neuropathy and high levels of motilin

A reduction of gallbladder emptying in response to neural or hormonal stimulation has been reported in patients with diabetes mellitus. Decreased gallbladder emptying may be a key factor in the pathogenesis of gallbladder stones. Few drugs, if any, are able to stimulate gallbladder emptying. However, in a previous study we demonstrated that erythromycin, a macrolide antibiotic, stimulates gallbladder emptying and motilin release in healthy human subjects by an atropine-sensitive pathway. Therefore, the present study was designed to evaluate the effect of erythromycin on gallbladder emptying and motilin release in diabetic patients with or without cardiac autonomic neuropathy (AN). Thirteen diabetic patients, six with AN, and 10 healthy subjects were enrolled in the study protocol. Gallbladder emptying was determined by sonography after ingestion of a standard meal and during infusion of erythromycin alone or together with 6 g/kg/hr atropine. We found that 100 mg/hr erythromycin caused a significant reduction in gallbladder volume in both healthy subjects and diabetic patients. The ejection fraction (mean ±se) of 45.3±8.2% and 37.3±5.0% was similar. The presence of AN had no influence on gallbladder emptying induced by erythromycin. Basal motilin plasma levels were 111.5±14.5 pmol/liter in diabetic patients and 63.3 ±6.0 pmol/liter in healthy subjects (P<0.01). However, patients with AN had higher (130.0 ±11.9 pmol/liter) motilin plasma levels than patients without (74.0±9.4 pmol/liter,P<0.01). Erythromycin administration caused an approximately twofold increase in plasma motilin concentrations in healthy subject and patients withou AN, but did not stimulate motilin release in neuropathic patients. A negative correlation (r=–0.75,P<0.01) was found between basal plasma levels of motilin and peak of gallbladder emptying induced by erythromycin. Atropine completely inhibited the effects of erythromycin on gallbladder emptying and motilin release (P<0.001 by ANOVA). A negative correlation (r=–0.52,P<0.05) was also found between plasma glucose concentrations and peak of gallbladder emptying. Present results demonstrate that erythromycin could be used for treating alterations of gallbladder emptying in diabetic patients with or without AN.     

Liposomal daunorubicin versus standard daunorubicin: long term follow-up of the GIMEMA GSI 103 AMLE randomized trial in patients older than 60 years with acute myelogenous leukaemia

This randomized phase III clinical trial explored the efficacy of DaunoXome (DNX) versus Daunorubicin (DNR) in acute myeloid leukaemia (AML) patients aged >60 years. Three hundred and one AML patients were randomized to receive DNR (45 mg/m(2) days 1-3) or DNX (80 mg/m(2) days 1-3) plus cytarabine (AraC; 100 mg/m(2) days 1-7). Patients in complete remission (CR) received a course of the same drugs as consolidation and then were randomized for maintenance with AraC+ all trans retinoic acid or no further treatment. Among 153 patients in the DNR arm, 78 (51.0%) achieved CR, 55 (35.9%) were resistant and 20 (13.1%) died during induction. Among 148 patients in the DNX arm, 73 (49.3%) achieved CR, 47 (31.8%) were resistant and 28 (18.9%) died during induction. Univariate analysis showed no difference as to induction results. After CR, DNX showed a higher incidence of early deaths (12.5% vs. 2.6% at 6 months, P = 0.053) but a lower incidence of relapse beyond 6 months (59% vs. 78% at 24 months, P = 0.064), with a cross in overall survival (OS) and disease-free survival (DFS) curves and a later advantage for DNX arm after 12 months from diagnosis. DNX seems to improve OS and DFS in the long-term follow-up, because of a reduction in late relapses.     

A Decreased Response to Resistin in Mononuclear Leukocytes Contributes to Oxidative Stress in Nonalcoholic Fatty Liver Disease

Digestive Diseases and Sciences - Deregulation of immune response and oxidative stress contribute to nonalcoholic fatty liver disease (NAFLD) pathogenesis. Resistin is a physiological modulator of...     

Treatment of DVT: how long is enough and how do you predict recurrence

Abstract Currently available anticoagulants are effective in reducing the recurrence rate of venous thromboembolism (VTE). However, anticoagulant treatment is associated with an increased risk for bleeding complications. Thus, anticoagulation has to be discontinued when benefit of treatment no longer clearly outweigh its risks. The duration of anticoagulant treatment is currently framed based on the estimated individual risk for recurrent VTE. The incidence of recurrent VTE can be estimated through a two-step decision algorithm. Firstly, the features of the patient (gender), of the initial event (proximal or distal deep vein thrombosis or pulmonary embolism), and the associated conditions (cancer, surgery, etc) provide essential information on the risk for recurrence after anticoagulant treatment discontinuation. Secondly, at time of anticoagulant treatment discontinuation, d-dimer levels and residual thrombosis have been indicated as predictors of recurrent VTE. Current evidence suggests that the risk of recurrence after stopping therapy is largely determined by whether the acute episode of VTE has been effectively treated and by the patient’s intrinsic risk of having a new episode of VTE. All patients with acute VTE should receive oral anticoagulant treatment for three months. At the end of this treatment period, physicians should decide for withdrawal or indefinite anticoagulation. Based on intrinsic patient’s risk for recurrent VTE and for bleeding complications and on patient preference, selected patients could be allocated to indefinite treatment with VKA with scheduled periodic re-assessment of the benefit from extending anticoagulation. Alternative strategies for secondary prevention of VTE to be used after conventional anticoagulation are currently under evaluation. Cancer patients should receive low molecular-weight heparin over warfarin in the long-term treatment of VTE. These patients should be considered for extended anticoagulation at least until resolution of underlying disease. Abbreviated abstract The risk for recurrent venous thromboembolism can be estimated through a two-step algorithm. Firstly, the features of the patient (gender), of the initial event (proximal or distal deep vein thrombosis or pulmonary embolism), and the associated conditions (cancer, surgery, etc) are essential to estimate the risk for recurrence after anticoagulant treatment discontinuation. Secondly, a correlation has been shown between d-dimer levels and residual thrombosis at time of anticoagulant treatment discontinuation and the risk of recurrence. Currently available anticoagulants are effective in reducing the incidence of recurrent venous thromboembolism, but they are associated with an increased risk for bleeding complications. All patients with acute venous thromboembolism should receive oral anticoagulant treatment for three months. At the end of this treatment period physicians should decide for definitive withdrawal or indefinite anticoagulation with scheduled periodic re-assessment of the benefit from extending anticoagulation.