Frontal Theta Asymmetry as a Biomarker of Depression.

INTRODUCTION: Electroencephalography (EEG) has been used extensively to study affective disorders. Quantitative spectral analysis of an EEG scan has been used to assess the biological basis of emotional disorders such as depression as well as to investigate biomarkers of affective disorders. Inter-hemispheric asymmetries in both baseline and stimulus-evoked frequencies (alpha, beta, theta, and delta) are potential biomarkers of depression. The role of frontal alpha asymmetry has been established, but other spectral frequencies such as frontal theta remain elusive. We compared the hemispheric differences in frontal theta power in depressed patients and controls before and during listening to music to study the correlation of frontal theta asymmetry with depression. METHODS: To determine whether stimulus-evoked frontal theta asymmetry is a biomarker of depression, we compared 23 patients with mild depression (based on the Hamilton Depression Rating Scale) with 17 age- and sex-matched controls by conducting EEG at rest and after listening to Indian classical music. RESULTS: In controls without depression, the mean frontal theta power of the left hemisphere and frontal theta asymmetry increased significantly during music listening. In depressed patients, frontal theta asymmetry was reversed during music listening. CONCLUSION: Frontal theta asymmetry is a potential biomarker of depression.

Urinary high-mobility group box-1 associates specifically with lupus nephritis class V.

INTRODUCTION: High-mobility group box 1 protein (HMGB-1) has been implicated in the pathogenesis of lupus nephritis (LN). There is increased HMGB-1 expression in the kidneys and increased levels are observed in serum and urine of patients with LN. This study was performed to determine whether the increased urinary HMGB-1 was specific for active lupus or secondary to renal damage. METHODS: Urine from 61 lupus patients (32 had active LN and 29 had systemic lupus erythematosus (SLE) with no evidence of LN) and 14 control proteinuric patients (all with hypertension and eight also with diabetes) were included in this study. HMGB-1 was detected by Western blot. Urine protein was normalized to urine creatinine to account for volume of the specimen. RESULTS: Median normalized urine HMGB-1 levels were significantly elevated in LN patients compared to lupus patients without kidney disease (53.81 vs 9.46, p < 0.001). A difference in median levels was seen between LN classes, with a significant difference between proliferative and membranous disease (33.4 vs 138.8, p = 0.003). Urine protein to urine creatinine ratio (P/C) correlated with urinary HMGB-1 (r = 0.52, p < 0.001), but across the classes this was true only for membranous disease (r = 0.71, p = 0.022, proliferative, p = 0.63; mixed, p = 0.34). CONCLUSIONS: HMGB-1 is elevated in the urine of patients with active LN. Levels are associated with LN class, and higher levels of urinary HMGB-1 are seen in patients with class V when compared to both proliferative and mixed classes. Therefore, urinary HMGB-1 may be suggestive of membranous LN and warrants further evaluation in a large lupus cohort.

Differential regulation of cell death programs in males and females by Poly (ADP-Ribose) Polymerase-1 and 17ß estradiol.

Cell death can be divided into the anti-inflammatory process of apoptosis and the pro-inflammatory process of necrosis. Necrosis, as apoptosis, is a regulated form of cell death, and Poly-(ADP-Ribose) Polymerase-1 (PARP-1) and Receptor-Interacting Protein (RIP) 1/3 are major mediators. We previously showed that absence or inhibition of PARP-1 protects mice from nephritis, however only the male mice. We therefore hypothesized that there is an inherent difference in the cell death program between the sexes. We show here that in an immune-mediated nephritis model, female mice show increased apoptosis compared to male mice. Treatment of the male mice with estrogens induced apoptosis to levels similar to that in female mice and inhibited necrosis. Although PARP-1 was activated in both male and female mice, PARP-1 inhibition reduced necrosis only in the male mice. We also show that deletion of RIP-3 did not have a sex bias. We demonstrate here that male and female mice are prone to different types of cell death. Our data also suggest that estrogens and PARP-1 are two of the mediators of the sex-bias in cell death. We therefore propose that targeting cell death based on sex will lead to tailored and better treatments for each gender.

Calcium channel blockers and the CVS reflex responses during lower body suction.

Nine normal men (mean age 27.6 yr) were exposed to continuous lower-body suction pressure (LBSP) of -20 to -50 mmHg (for 5 min at each level) on four different occasions after having consumed a single oral therapeutic dose of either diltiazem, nifedipine, verapamil, or a placebo, randomly, in a single blind manner. The suction was applied at 12.30 pm in all experiments, while the medications were administered in such a manner so that their expected peak plasma levels would have been achieved at the time of suction application. The cardiovascular reflex effects commenced at a pressure of -30 mmHg, and peaked at -50 mmHg. The increases in the heart rate for all treatments at -50 mmHg was statistically similar (about 16-20 beats/min). The systolic BP fell by about 9 mmHg for the placebo experiments, and this change was not different from the changes produced by the 3 Calcium channel blocker treatments. The diastolic BP increase was about 3 mmHg. The Cardiac index did not vary significantly. Our results suggest that the commonly used Ca++ channel blockers do not adversely affect orthostatic tolerance.

Peak expiratory flow rates in elderly Indians.

Peak expiratory flow rates were measured in 124 normal elderly men (55-85 yr) using the Wright's peak flow meter. In the less than 60 yrs age group (n = 32; mean age 57.7 yr) the PEFR was 431 +/- 13 lpm, while for the group greater than 60 yr (mean age 69.0 +/- 6.0; n = 92), the PEFR value was 373 +/- 11 1pm. These values are similar to those reported in other Indian studies, suggesting that the ethnic variations amongst Indian subjects do not affect the PEFR. However, the reported values are lower than those observed in Europeans, but greater than those of Chinese. The PEFR regressed at a rate of 4.47 1pm/year increase in age, but is positively correlated to the subjects' height (cm), and their FVC and FEVI. The smokers had a significantly higher PEFR as compared with the non-smokers. This finding was contrary to what was expected.