Body fat mass and lean mass as predictors of survival in hemodialysis patients.

A higher body mass index (BMI) is a predictor of better survival in hemodialysis patients, although the relative importance of body fat and lean mass has not been examined in the dialysis population. We performed an observational cohort study in 808 patients with end-stage renal disease on maintenance hemodialysis. At baseline, fat mass was measured by dual-energy X-ray absorptiometry and expressed as fat mass index (FMI; kg/m2). Lean mass index (LMI) was defined as BMI minus FMI. During the mean follow-up period of 53 months, 147 deaths, including 62 cardiovascular (CV) and 85 non-CV fatal events, were recorded. In univariate analysis, LMI was not significantly associated with CV or non-CV death, whereas a higher FMI was predictive of lower risk for non-CV death. Analyses with multivariate Cox models, which took other confounding variables as covariates, indicated the independent associations between a higher LMI and a lower risk of CV death, as well as between a higher FMI and a lower risk of non-CV death. These results indicate that increased fat mass and lean mass were both conditions associated with better outcomes in the dialysis population.

Inhibition of K(+)-evoked release of rat striatal 5-hydroxytryptamine by an atypical antidepressant: trazodone.

Using microdialysis, extracellular concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the striatum of rats. In rats given trazodone, m-chlorophenylpiperazine dihydrochloride, or imipramine, the concentrations of 5-HT were unchanged. 5-HIAA in trazodone- or imipramine-treated rats, however, was respectively, decreased to 80 or 65% of preinjections levels. When the potassium concentration (K(+)) was increased up to 150 mmol/l in the perfusate, the concentrations of 5-HT increased to about ten times the basal levels in the rats given saline. In rats treated with trazodone, K(+)-evoked elevations of 5-HT were less than five times the basal level. Multiple trazodone administrations prolonged the duration of inhibition of 5-HT release. In rats treated with other drugs, the K(+)-evoked 5-HT release was not affected. These observations suggest that trazodone itself might reduce 5-HT neural transmission.

Electrophysiologic analysis of antidepressant drug effects on the GABA(A) receptor complex based upon antagonist-induced encephalographic power spectrum changes.

To better understand antidepressant drug effects on the GABA(A) receptor complex (the GABA(A) receptor, chloride ionophore and benzodiazepine receptor), we investigated how antidepressants influenced power spectrum changes induced by pentylenetetrazol (PTZ), a chloride ionophore antagonist, in the rat hippocampal electroencephalogram (EEG). In control recording, PTZ (27.5 mg/kg i. p.) increased EEG power at frequencies under 12 Hz up to five times. After rats were pretreated with imipramine, fluoxetine or trazodone for 7 days (10 mg/kg i.p., twice a day), PTZ could not increase EEG power to more than three times the power before injection; this effect was not observed after pretreatment for 3 days. These three antidepressants inhibit serotonin uptake, while two other antidepressants, desipramine and nortriptyline, that inhibit norepinephrine uptake failed to counter the PTZ effect. We concluded that antidepressants with serotonergic effects enhanced the function of the GABA(A) receptor complex.

[A study of the effects of antidepressants on the GABAA receptor and its complex based on the drug actions on the power-spectral changes of rat hippocampal EEG induced by GABA antagonists and inverse agonists].

To analyze the effects of antidepressants on the GABAA receptor, we investigated how the chronic administration of antidepressants (10 mg/kg twice a day for three or seven days, ip) influenced the power-spectral changes induced by pentylenetetrazol (PTZ; a GABA antagonist; 27.5 mg/kg) or beta-carboline-3-carboxylic-acid-methylester (beta-CCM; an inverse agonist; 1 mg/kg) on rat hippocampal EEGs. PTZ and beta-CCM are known to inhibit the chloride ionophore and benzodiazepine receptor (GABAA receptor complex), respectively. After the ip injection of both compounds, the EEG power under 12 Hz increased to about five times that before injection. Between the rats that did not receive any antidepressants and all those injected with the drugs for 3 days or treated with desipramine (DMI) for 7 days, there were no apparent changes in the effect of PTZ or beta-CCM. However, in the rats treated with imipramine, fluoxetine or trazodone for 7 days, the increase in power after the injection of PTZ or beta-CCM was apparently suppressed. In these rats, the power values were less than three times those before the dosing of PTZ or beta-CCM. DMI is known to inhibit the re-uptake of norepinephrine (NE), while the other three antidepressants inhibit that of serotonin (5-HT). Trazodone is also reported to block the 5-HT2 sites. These observations might indicate that the chronic administration of antidepressants prompted the function of the GABAA receptor complex. Moreover, it is also suggested that, to that action, the effect of antidepressants on the 5-HT system or interaction between the 5-HT system and GABA receptors might play some role.