Hydrogen peroxide-induced intracellular acidosis and electromechanical inhibition in the diseased human ventricular myocardium

Accumulation of oxygen free radicals is an important mediator of post-ischemia/reperfusion cardiac dysfunction. However, oxidative injury has not been well characterized in human cardiac tissues. In the present study, we superfused hydrogen peroxide (H(2)O(2)) into the diseased human ventricle in order to assess the effects of oxygen free radicals on the electromechanical parameters and the intracellular pH (pH(i)), and to test the ability of certain potential cardioprotective agents, including scavengers of hydrogen peroxide (dibenzamidostilbene disulfonic acid; DBDS), the.OH free radical (N-(mercaptopropionyl)-glycine; N-MPG), and the HOCl free radical (L-methionine), to protect against oxidative injury. Disease human ventricular tissues were obtained from patients undergoing heart transplantation. Electrophysiological experiments were performed using a traditional micropipette, while the pH(i) was measured by microspectrofluorimetry. We found that (a) H(2)O(2) (30 microM-3 mM) induced a significant dose-dependent intracellular acidosis, (b) H(2)O(2) (30 microM-3 mM) had a notable dose-dependent biphasic effect on the contractile force (an increase, followed by a decrease), while moderate concentrations of H(2)O(2) also inhibited the generation of action potential and increased the diastolic resting force significantly, and (c) N-MPG caused significant block of both the intracellular acidosis and the electromechanical inhibition induced by 3 mM H(2)O(2), whereas L-methionine and DBDS did not. Our data suggest that the toxic effects of H(2)O(2) are caused mainly through the generation of.OH, which is attributed to the intracellular acidosis seen in the diseased human ventricle.     

Rewarding effects of ethanol and cocaine in µ opioid receptor-deficient mice

To investigate the role of mu opioid receptors in the reinforcing effects of psychotropic drugs, the voluntary ethanol intake and ethanol- and cocaine-induced conditioned place preference in mu opioid receptor-deficient mice and their wild-type counterpartners was tested. Moreover, dopamine D1 and D2 receptor binding was measured. It was found that ethanol intake was significantly lower in deficient mice. Conditioned place preference in wild-type animals was induced with 5.0 mg/kg cocaine and this dose was ineffective in the knockouts. In this group conditioned place preference occurred after injection of 10.0 mg/kg cocaine. Cocaine induced a similar increase in locomotor activity in both groups of mice. There was no difference in dopamine D1 receptor binding, whereas dopamine D2 receptor binding was significantly lower in the hippocampus of deficient animals. This suggests that interaction between opioid systems and dopaminergic systems may account for the differences in responding to the drugs.     

Analysis of gene expression in the developing mouse retina

In the visual system, differential gene expression underlies development of the anterior-posterior and dorsal-ventral axes. Here we present the results of a microarray screen to identify genes differentially expressed in the developing retina. We assayed gene expression in nasal (anterior), temporal (posterior), dorsal, and ventral embryonic mouse retina. We used a statistical method to estimate gene expression between different retina regions. Genes were clustered according to their expression pattern and were ranked within each cluster. We identified groups of genes expressed in gradients or with restricted patterns of expression as verified by in situ hybridization. A common theme for the identified genes is the differential expression in the dorsal-ventral axis. By analyzing gene expression patterns, we provide insight into the molecular organization of the developing retina.     

The effects of hypertonic saline solution (7.5%) on coagulation and fibrinolysis: an in vitro assessment using thromboelastography

We studied the effects of hypertonic (7.5%) and normal saline on coagulation and fibrinolysis in an in vitro model using thromboelastography of human whole blood. Reaction times increased and alpha angles decreased with hypertonic saline replacement at 7.5% blood volume compared with similar dilution with normal saline. At 10% blood volume replacement with hypertonic saline, reaction and coagulation times were significantly increased and alpha angles were decreased. Clot lysis at 30 min was also significantly reduced. We conclude that 7.5% hypertonic saline solution has anticoagulant effects if it replaces 7.5% or more of blood volume.     

The performance properties of the International Index of Erectile Function (IIEF-15) in assessing erectile dysfunction in patients with lower urinary tract symptoms

To validate the International Index of Erectile Function (IIEF-15) in Malaysian population. Reliability and internal consistency were evaluated using the test-retest method and Cronbach's alpha. Sensitivity to change was expressed as the effect size index. Internal consistency was excellent (Cronbach's alpha value = 0.75 to 0.90) Test-retest correlation coefficient and intraclass correlation coefficient were highly significant (ICC = 0.75 and above) and a high degree of sensitivity and specificity was observed. The IIEF-15 is suitable, reliable, valid and sensitive to clinical change in the Malaysian population.     

Profile of women presenting for abortions in Singapore at the National University Hospital

The study was conducted to profile women seeking abortions at the National University Hospital, with particular interest in the trend of teenage pregnancies with the aim of identifying risk factors for late presentation for abortions. All patients who underwent an abortion at our center from January 1, 1996 to December 31, 2000 were recruited. Data were entered into a prepared questionnaire during the mandatory pre-abortion counseling sessions and completed at the 6-week post-abortion follow-up. This was then keyed into a database (SPSS Version 10), and the results were analyzed. Multivariate analysis was used in identifying risk factors associated with late presentation for abortions. Chi-square analysis of variables was used where relevant. A total of 1370 women presented for induced abortions during the period of study. The mean age of women was 29.6 years. Most women were either homemakers (35.3%) or semi-skilled workers (28.5%) with at least a secondary school education (58.3%). The majority were married (75.5%). There was a significant trend in the proportion of single women seeking abortions, from 18.3% in 1996 to 27.8% in 2000 (p < 0.05). At the same time, the proportion of women presenting for repeat abortions also increased from 13.8% in 1996 to 33.2% in 2000 (p < 0.05). Teenage abortions made up 117 (8.5%) of the study group, of which 95% were single women. Significant proportions (52.1%) were students at the time of abortion. In contrast to women above 20 years of age, pregnant teenagers were more likely not to have used any contraception (67.1% vs. 37.3%) and more likely to present late for abortion (18.8% vs. 10.4%). Teenage pregnancies are a major risk factor for late presentation for abortions. This emphasizes the need for availability and easy access to early abortion counseling, and the need for sex education with use of contraception starting in schools, to reduce abortions among teenagers.     

Relapsed and late-onset Nipah encephalitis

An outbreak of infection with the Nipah virus, a novel paramyxovirus, occurred among pig farmers between September 1998 and June 1999 in Malaysia, involving 265 patients with 105 fatalities. This is a follow-up study 24 months after the outbreak. Twelve survivors (7.5%) of acute encephalitis had recurrent neurological disease (relapsed encephalitis). Of those who initially had acute nonencephalitic or asymptomatic infection, 10 patients (3.4%) had late-onset encephalitis. The mean interval between the first neurological episode and the time of initial infection was 8.4 months. Three patients had a second neurological episode. The onset of the relapsed or late-onset encephalitis was usually acute. Common clinical features were fever, headache, seizures, and focal neurological signs. Four of the 22 relapsed and late-onset encephalitis patients (18%) died. Magnetic resonance imaging typically showed patchy areas of confluent cortical lesions. Serial single-photon emission computed tomography showed the evolution of focal hyperperfusion to hypoperfusion in the corresponding areas. Necropsy of 2 patients showed changes of focal encephalitis with positive immunolocalization for Nipah virus antigens but no evidence of perivenous demyelination. We concluded that a unique relapsing and remitting encephalitis or late-onset encephalitis may result as a complication of persistent Nipah virus infection in the central nervous system.