Sperm binding to hyaluronan is an excellent predictor of Nili-Ravi buffalo bull fertility

This study reports the first evaluation of sperm hyaluronan binding assay (HBA) for predicting the fertility of Nili-Ravi buffalo bulls in relation to standard parameters of sperm quality. Cryopreserved semen doses of low (n = 6), medium (n = 3) and high fertility (n = 8) bulls based on their respective return rates were used. Significantly, more spermatozoa bound to hyaluronan from the most fertile bulls (57.15% ± 1.44) compared with medium (42.46% ± 1.08) and low fertility bulls (29.70% ± 0.78). A strongly positive correlation (r = .824, p < .01) was found between HBA and fertility that predicts a 67.9% variability (r² = .679, p < .01) in fertility. HBA was also strongly positively correlated with sperm viability (r = .679, p < .01) followed by their live/dead ratio (r = .637, p < .01), uncapacitated spermatozoa (r = .631, p < .01), normal apical ridge (r = .459, p < .01), motility (r = .434, p < .01), mature spermatozoa with low residual histones (r = .364, p < .01), high plasma membrane integrity (r = .316, p < .01) and nonfragmented DNA levels (r = .236, p < .05). It was negatively correlated with spermatozoa having reacted acrosome (r = −.654, p < .01). A fertility model built using a combination of sperm HBA and either sperm livability or viability predicts, respectively, 86.1% (r² = .861, p < .01) and 85.9% (r² = .859, p < .01) variability in buffalo bull fertility. In conclusion, sperm HBA may prove to be a single robust predictor of Nili-Ravi buffalo bull fertility.     

Chronic high-frequency stimulation of the subthalamic nucleus and L-DOPA treatment in experimental parkinsonism: effects on motor behaviour and striatal glutamate transmission

Hyperactivity of striatal glutamatergic synaptic transmission in response to dopamine depletion plays a major role in the pathogenesis of parkinsonian motor symptoms. In the present study we investigated the impact, on this hyperactivity, of chronic dyskinesiogenic L-DOPA treatment, combined or not with high-frequency stimulation (HFS) of the subthalamic nucleus (STN). In vitro patch-clamp recordings were performed from striatal spiny neurons of hemiparkinsonian rats (intranigral 6-OHDA injection). Here we show that dyskinesiogenic L-DOPA treatment exacerbated striatal glutamatergic hyperactivity induced by 6-OHDA lesion. Chronic 5-day STN HFS had the opposite effect, reducing striatal glutamatergic transmission in both parkinsonian and dyskinetic animals. Consistently, chronic HFS stimulation could progressively ameliorate motor parkinsonian signs (akinesia) but, conversely, did not improve L-DOPA-induced dyskinesia (LID). Thus, the effects of L-DOPA and HFS on corticostriatal transmission seem to be dissociated. These data show for the first time that dyskinesiogenic L-DOPA treatment and chronic STN HFS with antiakinetic effects induce opposite plastic rearrangements in the striatum. The interaction between these two treatments provides further evidence that striatal glutamatergic hyperactivity is a pathophysiological correlate of akinesia rather than LID.     

Inhibition of microparticle release triggers endothelial cell apoptosis and detachment

Endothelial cell cultures contain caspase 3-containing microparticles (EMP), which are reported to form during or after cell detachment. We hypothesize that also adherent endothelial cells release EMP, thus protecting these cells from caspase 3 accumulation, detachment and apoptosis. Human umbilical vein endothelial cells (HUVEC) were incubated with and without inhibitors of microparticle release (Y-27632, calpeptin), both in the absence or presence of additional "external stress", i.e. the apoptotic agent staurosporin (200 nM) or the activating cytokine interleukin (IL)-1alpha (5 ng/ml). Control cultures contained mainly viable adherent cells and minor fractions of apoptotic detached cells and microparticles in the absence of inhibitors. In the presence of inhibitors, caspase 3 accumulated in adherent cells and detachment tended to increase. During incubation with either staurosporin or IL-1alpha in the absence of inhibitors of microparticle release, adherent cells remained viable, and detachment and EMP release increased slightly. In the presence of inhibitors, dramatic changes occurred in staurosporin-treated cultures. Caspase 3 accumulated in adherent cells and >90% of the cells detached within 48 hours. In IL-1alpha-treated cultures no accumulation of caspase 3 was observed in adherent cells, although detachment increased. Scanning electron microscopy studies confirmed the presence of EMP on both adherent and detached cells. Prolonged culture of detached cells indicated a rapid EMP formation as well as some EMP formation at longer culture periods. Inhibition of EMP release causes accumulation of caspase 3 and promotes cell detachment, although the extent depends on the kind of "external stress". Thus, the release of caspase 3-containing microparticles may contribute to endothelial cell survival.     

Pre-admission warfarin use in patients with acute ischemic stroke and atrial fibrillation: The appropriate use and barriers to oral anticoagulant therapy

INTRODUCTION: Warfarin reduces the risk of stroke in patients with atrial fibrillation. Despite strong guideline recommendations, studies continue to demonstrate the under-use of warfarin in clinical practice. PURPOSE: To determine the prevalence and predictors of warfarin use in patients presenting with atrial fibrillation and acute ischemic stroke who do not have a documented contraindication to anticoagulants. METHODS: We conducted a retrospective chart review of all patients admitted to the Hamilton General Hospital with a primary diagnosis of ischemic stroke and a coded diagnosis of atrial fibrillation between 1999 and 2004. Using a standardized data abstraction form, the following variables were recorded: baseline demographics, past medical history including risk factors for stroke and major bleeding and known predictors of warfarin under-use. In cases where warfarin was not prescribed, charts were also reviewed for documented contraindications to warfarin use. The following were considered valid contraindications to warfarin: patient refusal, non-compliance with INR monitoring, bleeding diathesis, history of major bleeding or significant alcohol consumption. RESULTS: In total, 196 patients with ischemic stroke and atrial fibrillation were identified. Of these patients, 106 were considered to be appropriate candidates for anticoagulation after excluding patients with no known diagnosis of atrial fibrillation prior to admission (N=59), a valid contraindication to warfarin use (N=18), a CHADS2 score <1 (N=6) or a competing diagnosis for warfarin use (N=7). Of the patients deemed to be suitable candidates for warfarin, 57 (54%) were receiving warfarin therapy on admission. On multivariable analyses, increasing age (OR 0.7; 95% CI 0.5-0.9) was associated with a reduced odds of warfarin use while a history of stroke or TIA (OR 2.6; 95% CI 1.1-6.5) and a history of congestive heart failure (OR 3.2; 95% CI 1.1-9.0) were associated with an increased odds of warfarin use in patients without a contraindication to warfarin. While 75% of patients <75 years old were anticoagulated, only 33% of those >85 years were prescribed warfarin on admission to hospital. CONCLUSIONS: early half of all patients presenting with atrial fibrillation and acute ischemic stroke who were suitable candidates for anticoagulation were not prescribed warfarin. In patients not prescribed warfarin, very few had a documented contraindication. Advanced age appears to be the strongest predictor of warfarin non-use.     

Obstructive sleep apnea and heart rate asymmetry microstructure during sleep

Purpose

Heart rate decelerations and accelerations have unequal input to heart rate variability (HRV) and patterns created by consecutive cardiac cycles—this phenomenon is known as heart rate asymmetry (HRA). The analysis of monotonic runs of heart rate decelerations and accelerations provides a detailed insight into the HRA microstructure and thus of HRV.

Aim

To evaluate the relation between the severity of obstructive sleep apnea (OSA) and the HRA microstructure during sleep.

Methods

Seventy-eight patients with suspected OSA underwent overnight polysomnography. The 300-min ECGs from the polysomnography were selected and analyzed. The HRA microstructure was quantified by measuring (1) the contribution of monotonic runs of decelerations or accelerations of different lengths to the number of all sinus beats, and (2) the length of the longest deceleration and acceleration runs.

Results

There were 19 patients with no/mild OSA (Apnea/Hypopnea Index (AHI) 5.1 ± 2.5/h), 18 with moderate OSA (AHI 21.8 ± 4.0/h) and 41 with severe OSA (AHI 42.8 ± 17.4/h). Patients with severe OSA had significantly reduced deceleration and acceleration runs of length 1 compared to the moderate OSA group, and compared to patients with no/mild OSA they had an increased number of longer runs (from 5 to 10 for accelerations and from 5 to 8 for decelerations; p < 0.05 for all comparisons). The longest acceleration runs were significantly longer in severe OSA group (p < 0.05) than in subjects with no/mild OSA.

Conclusions

HRA microstructure is related with OSA severity. An increased number of longer deceleration and acceleration runs is more common in severe OSA patients.     

The G1057D polymorphism of IRS-2 gene is not associated with type 2 diabetes and obese patients among ethnic groups in Tunisian population

BackgroundType 2 of diabetes is the most common metabolic disorder and results from the interaction between genetic and environmental factors. Insulin receptor substrate-2 (IRS-2), one of the major substrates of the insulin receptor, has a crucial role in insulin signalling and in beta cell development and survival. While several polymorphisms have been identified in the IRS-2 gene, the association of the Gly1057Asp polymorphism with type 2 diabetes has been studied in European and Chinese populations, but the results have been inconsistent.ObjectivesThe aim of this study was to investigate the association of Gly1057Asp polymorphism in insulin receptor substrate-2 (IRS-2) gene among patients with type 2 diabetes in well defined ethnic groups from Djerba Island in Southeastern Tunisia.MethodsThe studied population (172 Arabs and 100 Berbers) includes 162 patients with type 2 diabetes and 110 healthy controls. BMI was calculated for each subject. The subjects were unrelated and randomly selected Arabs and Berbers were equally distributed between controls and diabetics. The G1057D polymorphism of the IRS-2 gene was genotyped using PCR-RFLP assay.ResultsThis case/control study indicated that frequency of the IRS-2 Gly1057Asp polymorphism was not significantly different between the healthy controls and type 2 diabetic groups, neither between healthy nor obese subjects, in both ethnic groups. Moreover, this polymorphism is present at a lower frequency in Djerbian than in neighbouring European populations.ConclusionThese results strongly argue against a major role of the Gly1057Asp IRS-2 polymorphism in the pathogenesis of type 2 diabetes in Djerbian subjects.