Sex and strain differences in adult mouse cardiac repolarization: importance of androgens.
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OBJECTIVE: Gender differences in mouse cardiac repolarization have been reported to be due to the stimulatory action of androgens on the ultrarapid delayed rectifier K(+) current (I(Kur)) and its underlying Kv1.5 channel. To confirm the regulation of ventricular repolarization by androgens, the present study compared two strains of mice (CD-1 and C57BL/6) that present different androgen levels. METHODS AND RESULTS: Measurement of testosterone levels in different strains of mice (CD-1, C57BL/6, C3H and FVB) revealed that male C57BL/6 mice had very low levels of testosterone, whereas males of the other strains displayed normal testosterone levels. Furthermore, whole-cell voltage clamp recordings in isolated ventricular myocytes showed that the current density of I(Kur) in male C57BL/6 mice was similar to that in female mice but smaller with respect to male CD-1 mice. Androgen replacement in male C57BL/6 mice as well as in castrated male CD-1 mice shortened ventricular repolarization, increased I(Kur) current density, and increased expression of Kv1.5 channels. CONCLUSION: Strain and gender differences observed in mouse cardiac repolarization can be explained by different androgen levels. As a consequence, androgens are major regulatory factors in cardiac repolarization and special attention should be paid to the hormonal status of the animal when studying hormonal regulation of cardiac repolarization. (+info)
Gender differences in brain activity generated by unpleasant word stimuli concerning body image: an fMRI study.
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BACKGROUND: We have previously reported that the temporomesial area, including the amygdala, is activated in women when processing unpleasant words concerning body image. AIMS: To detect gender differences in brain activation during processing of these words. METHOD: Functional magnetic resonance imaging was used to investigate 13 men and 13 women during an emotional decision task consisting of unpleasant words concerning body image and neutral words. RESULTS: The left medial prefrontal cortex and hippocampus were activated only among men, and the left amygdala was activated only among women during the task; activation in the apical prefrontal region was significantly greater in men than in women. CONCLUSIONS: Our data suggest that the prefrontal region is responsible for the gender differences in the processing of words concerning body image, and may also be responsible for gender differences in susceptibility to eating disorders. (+info)
Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death.
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AIMS: Drug-induced QTc-prolongation, resulting from inhibition of HERG potassium channels may lead to serious ventricular arrhythmias and sudden death. We studied the quantitative anti-HERG activity of pro-arrhythmic drugs as a risk factor for this outcome in day-to-day practice. METHODS AND RESULTS: All 284,426 case reports of suspected adverse drug reactions of drugs with known anti-HERG activity received by the International Drug Monitoring Program of the World Health Organization (WHO-UMC) up to the first quarter of 2003, were used to calculate reporting odds ratios (RORs). Cases were defined as reports of cardiac arrest, sudden death, torsade de pointes, ventricular fibrillation, and ventricular tachycardia (n = 5591), and compared with non-cases regarding the anti-HERG activity, defined as the effective therapeutic plasma concentration (ETCPunbound) divided by the HERG IC50 value, of suspected drugs. We identified a significant association of 1.93 (95% CI: 1.89-1.98) between the anti-HERG activity of drugs, measured as log10 (ETCPunbound/IC50), and reporting of serious ventricular arrhythmias and sudden death to the WHO-UMC database. CONCLUSION: Anti-HERG activity is associated with the risk of reports of serious ventricular arrhythmias and sudden death in the WHO-UMC database. These findings are in support of the value of pre-clinical HERG testing to predict pro-arrhythmic effects of medicines. (+info)
Mouse model of post-infarct ventricular rupture: time course, strain- and gender-dependency, tensile strength, and histopathology.
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OBJECTIVE: Recent studies on mice with surgically induced acute myocardial infarction (AMI) have documented the frequent occurrence of ventricular rupture, an event not previously reported in other laboratory species. We have examined the natural history, histopathology and myocardial mechanical strength in mice with AMI. METHODS: AMI was induced by coronary artery occlusion and animals were monitored for fatal events. Gross and histological examinations were undertaken. RESULTS: Rupture occurred in the left ventricular free wall at 2-6 days after AMI. Incidence of rupture in male mice varied among three strains studied (3% for FVB/N, 27% for C57B/6J, and 59% for 129sv, P<0.05) and was lower in female than male mice (23% vs. 59%, P<0.05). Histologically, ruptured hearts had rapid-occurring and severe infarct expansion, multifocal intramural hemorrhage and leucoyte infiltration at the border zone and infarcted zone. In vitro, infarcted left ventricles demonstrated a 50-60% reduction in muscle tensile strength. This reduction preceded the onset of rupture and was related to the time-window of rupture and to infarct size. CONCLUSION: LV wall rupture in the mouse occurs within a narrow time-window after AMI and is strain- and gender-dependent. Infarct expansion, regional hemorrhage with formation of hematoma and leuocyte accumulation are important pathological changes leading to reduced myocardial tensile strength. (+info)
Women in cardiology: a European perspective.
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Women may be under-represented in cardiology in the UK, but what about the rest of Europe? (+info)
Regional variation of intracortical porosity in the midshaft of the human femur: age and sex differences.
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This study investigated age and sex differences in patterns of porosity distribution in the midshaft of the human femur. Cross-sections were obtained from 168 individuals from a modern Australian population. The sample comprised 73 females and 95 males, aged between 20 and 97 years. Microradiographs were made of 100-microm sections and pore and bone areas were determined using image processing software. Initially the sample was divided by age: young (20-44 years), middle (45-64 years) and old (65+ years), but it was found that analysis on the basis of the ratio of medullary area to total subperiosteal area gave clearer results. The cortex was divided into three rings radially and into octants circumferentially and the porosity of each segment was calculated. Results showed that a pattern with raised porosity in the posterior and anterolateral regions, and with greater porosity in the inner parts of the cortex, becomes more pronounced with age. In males this pattern develops steadily; in females there are much greater differences between the middle and older groups than earlier in life. The patterns observed are consistent with progressive bone loss occurring along a neutral axis of the cortex where bending stress is lowest and the mechanical advantage of the bone is least. (+info)
Healing after myocardial infarction.
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Wounding and healing are archaic principles, prerequisite for survival of any biologic material. However, strategies to cope with wounding may be quite different among organisms, species, or among various organs of one species. Today, myocardial infarction and the consequent loss of fully functional myocardium is the major aetiology for heart failure. Despite aggressive primary therapy, prognosis remains serious in patients with large infarction and severe left ventricular dysfunction. Thus, it would be highly desirable to influence healing of the cardiac wound to maintain structure and function of the heart. Herein, we review different, important factors of cardiac healing including reperfusion, mechanical stress, gender, and neurohormonal factors as well as specific factors essential for healing which may be genetic or acquired, emphasizing similarities and discrepancies between different organs and species. (+info)
The gender-specific impact of diabetes and myocardial infarction at baseline and during follow-up on mortality from all causes and coronary heart disease.
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OBJECTIVES: The goal of this study is to compare the magnitude of diabetes and myocardial infarction (MI) at baseline and during follow-up on cause-specific and all-cause mortality. BACKGROUND: History of both MI and diabetes are strong predictors of coronary heart disease (CHD) death. However, gender-specific data on the joint effect of diabetes and MI, and particularly on the effect of incident diabetes and MI developed during the follow-up, on CHD mortality are scarce. METHODS: The baseline cohort study included 2,416 patients with prior diabetes or MI at baseline; the follow-up cohort study included 4,315 patients with incident diabetes or MI diagnosed during the follow-up. RESULTS: In the baseline cohort study, men with prior MI had a 20% to 80% increased risk of CHD or total mortality, but women with prior MI had a 43% to 45% decreased risk of CHD or total mortality in comparison with men and women with prior diabetes. In the follow-up cohort study, men and women with incident MI had a higher risk of CHD mortality (hazard ratio [HR] 2.15 in men and 1.65 in women), and an almost similar risk of total mortality (HR 0.95 in men and 1.02 in women) in comparison with men and women with incident diabetes. CONCLUSIONS: In men, MI at baseline or during follow-up confers a greater risk on CHD mortality than diabetes does. In women, prior MI at baseline confers a lower risk on CHD mortality than prior diabetes does, but incident MI during follow-up confers a greater risk than incident diabetes does. In both men and women, total mortality is similar for incident MI and diabetes. (+info)