Caffeinol at the receptor level: anti-ischemic effect of N-methyl-D-aspartate receptor blockade is potentiated by caffeine.

BACKGROUND AND PURPOSE: Although caffeinol (a combination of a low dose of caffeine and ethanol) was shown to robustly reduce stroke damage in experimental models and is now in clinical evaluation for treatment of ischemic stroke, little is known about the potential mechanism of its action. METHODS: We used an in vivo excitotoxicity model based on intracortical infusion of N-methyl-D-aspartate (NMDA) and a model of reversible focal ischemia to demonstrate NMDA receptor inhibition as a potential mechanism of caffeinol anti-ischemic activity. RESULTS: Caffeinol reduced the size of excitotoxic lesion, and substitution of ethanol in caffeinol with the NMDA antagonists CNS-1102 and MK-801 but not with MgSO(4) produced treatment with strong synergistic effect that was at least as robust in reducing ischemic damage as caffeinol. This NMDA receptor antagonist and caffeine combination demonstrated a long window of opportunity, activity in spontaneously hypertensive rats, and, unlike caffeinol, was fully effective in animals chronically pretreated with ethanol. CONCLUSIONS: Our study suggests that antiexcitotoxic properties may underlie some of the anti-ischemic effect of caffeinol. This study provides strong evidence that the anti-ischemic effect of NMDA receptor blockers in general can be dramatically augmented by caffeine, thus opening a possibility for new use of NMDA-based pharmacology in the treatment of stroke.

Relation between markers of inflammation and estradiol in older men.

BACKGROUND: Inflammation plays a key role in the development of atherosclerosis. Studies in women receiving estrogens show their proinflammatory effects. This study sought to determine relation between sex hormones and 2 inflammation markers: C-reactive protein and fibrinogen. MATERIAL/METHODS: One hundred men of at least age 50 years were enrolled in the study. Plasma levels of total testosterone, estradiol, sex hormone binding globulin, high-sensitivity C-reactive protein, and fibrinogen were measured. Free estradiol and free testosterone were calculated. RESULTS: Estradiol and free estradiol levels were positively correlated with C-reactive protein and fibrinogen. In a subgroup analysis, this association persisted only in patients with stable coronary artery disease. No significant correlations were found between testosterone, free testosterone, sex hormone binding globulin, and markers of inflammation. CONCLUSIONS: This study suggests that estradiol may have proinflammatory effects in older men with coronary artery disease.

[Association of obesity and insulin resistance with serum testosterone, sex hormone binding globulin and estradiol in older males]. / Zwiazek miedzy otyloscia i insulinoopornoscia a stezeniem testosteronu, globuliny wiazacej hormony plciowe i estradiolu u starszych mezczyzn.

UNLABELLED: There is an increased accumulation of fat tissue with subsequent increase of insulin level, insulin resistance and decrease of testosterone level in aging males. AIM OF THE STUDY: Assessment of the relations between obesity, insulin resistance and levels of sex hormones. MATERIAL AND METHODS: Indices of obesity (BMI, WHR, waist circumference), insulin level, insulin resistance (HOMA-IR) and levels of sex hormones (total testosterone, free testosterone, free testosterone index, sex hormone-binding globulin--SHBG, estradiol) were measured in 107 males at the mean age of 60.1 +/- 7 years. RESULTS: Obesity among aging males is associated with insulin resistance and hyperinsulinism. All above factors correlate with decreased serum levels of testosterone and sex hormone binding globulin as well as increased ratio estradiol/testosterone ratio. CONCLUSION: Our data suggest a role of decreased levels of testosterone and SHBG in pathogenesis of visceral obesity and metabolic syndrome in older males.

[Sex hormones, HDL cholesterol and other lipoproteins in older males]. / Hormony plciowe, HDL cholesterol i inne frakcje lipoproteinowe u starszych mezczyzn.

UNLABELLED: The associations between sex hormones and cardiovascular risk factors in men are controversial. It is well known that testosterone level declines with age and this phenomenon is associated with increased incidence of cardiovascular disease in men. Elevated levels of total cholesterol and LDL cholesterol together with low HDL cholesterol are the important risk factors of coronary heart disease. THE AIM OF STUDY was to investigate the relationships between sex hormones and plasma lipids in aging males. MATERIAL: The study group comprised 107 males over 50 years old. RESULTS: A significant positive correlation was found between testosterone (T) and HDL-cholesterol (r=0.251; p<0.01). Estradiol level was inversely correlated with total cholesterol (r=-0.204; p<0.05). Interestingly, the older age of subjects was associated with increased levels of SHBG (r=0.28; p<0.01) and decreased free testosterone index (T/SHBG) (r=-0.423; p<0.001). CONCLUSION: These data support relationship between sex hormones and plasma lipids and suggest that a low testosterone concentration in aging males may be important in the pathogenesis of atherosclerosis.

Inverse relationship between total testosterone and anti-oxidized low density lipoprotein antibody levels in ageing males.

Accumulating evidence indicates the involvement of sex hormones in atherogenesis. Endogenous testosterone is inversely related to the majority of risk factors for atherosclerosis and is known to be a potent immunomodulator. Recently, autoantibodies to oxidized LDL (anti-oxLDL Ab) were shown to predict carotid and coronary atherosclerosis. The aim of this study was to investigate the relationship between these antibodies and testosterone level in ageing males. The study group comprised 65 males over 50 years old (42 with coronary artery disease). Serum anti-oxLDL Ab titer was measured by enzyme-linked immunoassay and total serum testosterone by radioimmunoassay. A significant inverse correlation was found between serum anti-oxLDL Ab titer and testosterone concentration (r=-0.346, P=0.0047). Alteration in serum anti-oxLDL Ab titres showed no correlation to classical cardiovascular risk factors, e.g. body mass index, waist/hip ratio, smoking, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol. In multiple regression analysis only testosterone level was independently associated with anti-oxLDL Ab. These data suggest a that fall of testosterone concentration in ageing men can influence either oxidative modification of LDL or the immune response to these lipoproteins which may be important in the pathogenesis of atherosclerosis.

Music preferences and tobacco smoking.

This study investigated the association of music preferences with tobacco smoking in a group of 152 high school and college students. Both the questionnaire and the listening survey indicated a higher preference for music associated with anxiety and depressed mood among smokers. These findings may reflect a common etiology of tobacco addiction and a specific type of music preferences. To elucidate this phenomenon further studies are needed.

Circadian rhythm of spectral indices of heart rate variability in healthy subjects.

Circadian pattern of heart rate variability spectral indices, including hourly, 24-hour, night, day, morning, and sex-adjusted measures of low frequency (LF), high frequency (HF), and LF/HF, was evaluated in healthy persons in 24-hour 3-lead electrocardiogram. HF showed circadian pattern with the greatest night values and LF/HF with the smallest night values. Peaks of hourly LF were found between 5 and 9 am and between 4 and 6 pm. The smallest LF was between 11 pm and 3 am. Hourly HF peaked between 11 pm and 5 am. The smallest HF was observed between midday and 2 pm. LF/HF peaked between 6 and 9 am as well as between 4 and 6 pm with the smallest values between midnight and 5 am. Sex adjustment was of no significance. In healthy subjects, HF and LF/HF have circadian pattern. Evaluation of all 5-minute intervals of 24-hour period seems to be a precise method of heart rate variability analysis.

Circadian rhythm of the QT interval dispersion in healthy subjects. Correlation with heart rate variability circadian pattern.

Circadian variation of QT interval dispersion (QTd) and heart rate variability spectral indices was evaluated in healthy persons in 24-hour 3-lead electrocardiogram. Mean values, SD, and SD/mean were evaluated for 24 hours, each hour separately and in night, day, and morning periods. Table Curve 2D and multiple regression were applied to find correlations between parameters. In 50% of subjects, a significant negative correlation was revealed between QTd and HF. Also, in 50% of persons, a significant positive correlation was found between QTd and low frequency/high frequency. After adjustment for periods, correlations were only observed during morning hours. With Table Curve 2D, 2 models of correlations between QTd and HF were found. Multiple regression analysis revealed relations between mean QTd and R-R as well as mean QTd and HF. It is possible that it is sympathovagal balance, as reflected in heart rate variability, and not the tone of both autonomic components that affects QTd variability.

Dihydrotestosterone treatment in men with coronary artery disease. I. Influence on sex hormones, lipid profile, insulin resistance and fibrinogen.

The effects of three months' transdermal dihydrotestosterone treatment were assessed in eleven men with coronary artery disease. Concentration of total testosterone level significantly decreased (p < 0.01) as well as free testosterone (p < 0.05) and estradiol levels (p < 0.01), without changes of sex hormone binding globuline and estradiol/testosterone ratio. DHT regimen did not alter the parameters of lipid profile. No changes of blood glucose, insulin, insulin resistance (HOMA) and fibrinogen were observed in this group. The tendency towards higher levels of hemoglobin, erythrocyte count and hematocrit did not reach statistical significance. Short term DHT administration in aging males was safe for prostate.

C-reactive protein: the pawn has been promoted to queen.

C-reactive protein (CRP) is one of the acute phase reactants that can increase its serum level up to 100- fold during systemic inflammation. Its clinical use was limited in the past because of its lack of specificity in differentiating infection from other inflammatory processes. With the advent of a high sensitivity assay, CRP was found to be a superb predictor in identifying apparently healthy men and women at risk for developing future cardiovascular events, such as heart attacks and strokes. CRP's predictive power is most likely due to its stability, reproducibility, and proatherogenic properties. Developing consensus to incorporate CRP determination into clinical practice guidelines will be the subject of intense debate and at the same time provide clinical research opportunities in the years to come.

Dihydrotestosterone treatment in men with coronary artery disease. II. Influence on myocardial ischemia and left ventricle.

The effect of transdermal dihydrotestosterone on left ventricle mass and its systolic and diastolic function as well as on the results of treadmill stress test was assessed in eleven males with coronary artery disease. DHT treatment for 3 months resulted in significant decrease in isovolumetric relaxation time (0.150+/-0.37 s vs. 0.135+/-0.03 s; p < 0.05) indicating the improvement of left ventricle diastolic function. Left ventricle mass and systolic function indices remained unchanged. There was improvement in myocardial ischemia, time to 1 mm ST segment depression increased (p < 0.05) and ST/HR slope decreased (p < 0.01). Correlation coefficients between testosterone concentration at the beginning of the study and differences in selected parameters of ECG stress test were as follows: for T and increased total exercise time (r= -0.83, p=0.002), for T and increased maximum workload (r= -0.84, p=0.001), for T and increased time to 1 mm ST segment depression (r= -0.75, p=0.009) and for T and decreased ST/HR slope (r=0.68, p=0.02).

Hypertension, and not sex hormones or insulin resistance affects left ventricular mass in aging men.

Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality. The aim of the study was to find which factors influence left ventricular mass (LVM) and whether relationships exist between sex hormones: testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG) and insulin resistance (HOMA-IR) and LVM. The study group consisted of 107 males at the age of over 50 years (mean 60.1 +/- 7.0). Positive significant correlations between LVM or left ventricle mass index (LVMI) and hypertension (0.23; p = 0.015 and 0.23; p = 0.019 respectively) as well as between LVM and body weight (0.38; p < 0.001) were observed. LVM and LVMI were higher in hypertensive than in normotensive men (279.9 +/- 82.2 vs. 243.4 +/- 70.3 g, p = 0.015 and 144.6 +/- 41.5 vs. 127.4 +/- 33.1 g/m2, p = 0.019 respectively). Multiple regression analysis showed LVM to be independently associated with hypertension and body weight. For LVMI such correlation was found only with hypertension. No relationships were observed between LVM/LVMI and insulin/insulin resistance.