P300 latency as an indicator of severity in major depressive disorder.

BACKGROUND: Depression is the most common mental health problem across all the age groups. Still diagnostic techniques and laboratory tests are awaited to confirm it. Some studies focus on P300 latency to aid in the diagnosis of depression. Hence, this study was conducted to know whether P300 latency is an indicator of major depressive disorder (MDD). METHODS: This study was conducted both on patients admitted in the hospital and those attending outdoor clinic giving written informed consent and fulfilling inclusion/exclusion criteria from the Department of Psychiatry, S.N. Medical College and Hospital, Agra. The sample consisted of 30 consecutive patients suffering from MDD as per the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and 30 subjects as normal control. Sociodemographic and clinical history proforma, Hamilton Rating Scale for Depression (Ham-D), and P300 were administered on all 60 subjects. Data were analyzed using mean, standard deviation, and t-test. RESULTS: Significant difference (P < 0.0001) has been found in HAM-D mean scores of depressed and nondepressed control group subjects. The mean score of depressed group was significantly high (18.066) compared to nondepressed control group (4.833). Significant difference (P < 0.0001) between the mean of P300 latency in depressed and nondepressed control subjects was also found. Mean score of P300 latency in depressed group was significantly high (346.918 ± 19.515) compared to the nondepressed control subjects (303.741 ± 6.378). There was a significant difference in the mean of P300 latency between mild and severe (P < 0.0001), mild and very severe (P < 0.0003), as well as moderate and severe (P < 0.0001) level of depression. CONCLUSIONS: P300 latency may be used as an indicator of MDD and it is directly proportional to the severity of MDD.

Liposome adjuvants prepared from the total polar lipids of Haloferax volcanii, Planococcus spp. and Bacillus firmus differ in ability to elicit and sustain immune responses.

Immune stimulating activity was compared for lipid vesicles consisting of the total polar lipids of an archaeon Haloferax volcanii, and the eubacteria Planococcus spp. and Bacillus firmus. Each total polar lipid extract readily formed liposomes of similar size, within which the protein antigen ovalbumin was entrapped, with comparable loading and internalization. Subcutaneous immunization of mice resulted in anti-ovalbumin antibody titers for all adjuvants, with memory recall responses that were significantly greater with the archaeal lipid (H. volcanii versus Planococcus). More striking, induction of cytotoxic T cell activity against the entrapped antigen, measured 10 days following a single vaccination (primary response) rapidly declined by week 7 (secondary response after injections on days 0 and 21) in mice immunized with Planococcus spp. liposomes, but was sustained in mice immunized with H. volcanii archaeosomes. Surprisingly, antigen free-Planococcus liposomes evoked potent non-specific inflammatory cytokine production (IL-12 and IL-6) by dendritic cells whereas archaeal H. volcanii vesicles evoked little inflammatory cytokines. This suggested that overt inflammatory response might not necessarily aid sustenance of immunity. B. firmus liposomes consisted of phosphatidylglycerol, phosphatidylethanolamine and cardiolipin and was an ineffective CTL adjuvant, even for initiating a primary response. Considering that the polar lipids of H. volcanii and Planococcus spp. both consist of the same lipid classes (sulfoglycolipids, phosphoglycerols, and cardiolipins), the unique ability of archaeosomes to maintain antigen-specific T cell immunity may be attributable to a property of the archaeal 2,3-diphytanylglycerol lipid core.

Molecular basis of the inhibition of gentamicin nephrotoxicity by daptomycin; an infrared spectroscopic investigation.

The lipopeptide daptomycin has been reported to reduce in vivo the nephrotoxicity of aminoglycoside antibiotics (Wood et al. (1989) Antimicrob. Agents Chemother. 33, 1280-1285; Beauchamp et al. (1990) Antimicrob. Agents Chemother. 34, 139-147). A recent dialysis study confirmed the existence of an electrostatic interaction between daptomycin and tobramycin (Couture et al. (1994) Antimicrob. Agents Chemother. 38, 742-749). The interaction of gentamicin with daptomycin and phosphatidylinositol (PI) dispersions was investigated by FTIR spectroscopy. We found no evidence of a direct interaction involving the neutralization of the aspartate groups of daptomycin by gentamicin and the amide I band of daptomycin did not reveal significant conformational changes of its peptidic moiety. On the other hand, daptomycin readily inserts within bilayers of PI, dimyristoylphosphatidylglycerol or dipalmitoylphosphatidylcholine, as judged from its influence on the fluidity of these bilayers. The incorporation of daptomycin into PI bilayers has no significant effect on the lipopeptide amide I band. Gentamicin also binds to PI bilayers and the associated modifications of the lipid bands are consistent with a tightening of the lipid network resulting from head group neutralization by gentamicin. The affinity of the aminoglycoside for PI is slightly increased in the presence of daptomycin, in agreement with the results of the dialysis study mentioned above. The lipid features indicate that its head group is still affected by gentamicin charges, but the thermotropic behavior of the hydrophobic portion becomes similar to that of the pure lipid. It is proposed that the contribution of daptomycin to the membrane charge density and its effect on the lipid packing both combine to counteract the inhibition of phospholipase activity due to aminoglycosides. Further work will attempt to determine how the peptide rings and gentamicin molecules are organized at the bilayer surface, how specific these interactions are and to confirm the influence of daptomycin on the phospholipid catabolism.

Daptomycin may attenuate experimental tobramycin nephrotoxicity by electrostatic complexation to tobramycin.

The lipopeptidic antibiotic daptomycin is reported to reduce experimental tobramycin nephrotoxicity (D. Beauchamp, M. Pellerin, P. Gourde, M. Pettigrew and M. G. Bergeron, Antimicrob. Agents Chemother. 34:139-147, 1990; C. A. Wood, H. C. Finkbeiner, S. J. Kohlhepp, P. W. Kohnen, and D. C. Gilbert, Antimicrob. Agents Chemother. 33:1280-1285, 1989). In an attempt to explain these results, the in vivo and in vitro interactions between daptomycin and tobramycin were studied. Tobramycin alone and preincubated with negatively charged phospholipid bilayers (liposomes) was dialyzed against increasing concentrations of daptomycin in buffer at pH 5.4. A significant drop in the concentration of tobramycin was observed when daptomycin was added to the opposite half cells. Furthermore, daptomycin induced a concentration-dependent release of lipid-bound tobramycin. Gold labeling experiments showed that daptomycin could be incorporated into phospholipid layers. Female Sprague-Dawley rats were treated with daptomycin alone, with tobramycin alone, or with the combination over 2 to 10 days. Levels of daptomycin and tobramycin in serum were similar in all groups. The levels of tobramycin in the renal cortex increased significantly with time and, on day 10, reached values of 654 +/- 122 and 844 +/- 298 micrograms/g of tissue (mean +/- standard deviation; not significant) in animals treated with tobramycin and the combination of daptomycin-tobramycin, respectively. No significant difference was observed in the levels of tobramycin in the kidneys between animals treated with tobramycin or the daptomycin-tobramycin combination at any time. By contrast, daptomycin levels were significantly higher in the renal cortexes of animals treated with daptomycin-tobramycin in comparison with those in the renal cortexes of animals treated with daptomycin alone on days 6,8, and 10 (P < 0.01). For immunogold labeling studies, animals were killed 4 h after a single injection of daptomycin alone or daptomycin in combination with tobramycin. Daptomycin was found throughout the matrixes of the lysosomes of proximal tubular cells of animals treated with daptomycin alone. In animals treated with the combination of daptomycin and tobramycin, daptomycin was associated with intralysosomal myeloid bodies. Our results suggest that daptomycin might attenuate experimental aminoglycoside nephrotoxicity by interacting with the aminoglycoside, perhaps electrostatically, and thereby protecting intracellular targets of toxicity.

Psychopathology of delayed resumption of sexual activity after myocardial infarction.

A total of 300 male cases of myocardial infarction were analyzed to evaluate the effect of myocardial infarction on sexual activity with particular stress on resumption of sexual activity and to determine the factors in cases of delayed resumption. Sexual activity decreased with age and correlated negatively to total sexual activity. 26 per cent cases developed one or other symptoms which occurred during all the phases of sexual activity but were more marked during resolution phase. Sexual activity returned to normal within six months only in 11.33 per cent cases and in the remaining cases resumption was delayed. In 27.8 per cent cases phobia of marked exertion involved in sex act, created by physicians in 12.7 per cent was the factor responsible for the delayed resumption. Quality of sexual activity decreased in 39 per cent cases and it was due to change in position from Male on top to male on bottom position in 31 per cent cases. Counselling for sexual rehabilitation has been discussed.

Adrenocortical dysfunction in depression: response to dexamethasone suppression test - a comparative study.

Thirty patients of Major Depressive Disorder, Schizophrenia and normal healthy controls each, received an overnight dexamethasone suppression test. Plasma and urinary Cortisol measurements showed that depressed patients had increased adrenocortical activity before dexamethasone and they showed an abnormal early escape from suppression which had a relationship with severity of depression. An attempt has been made to differentiate depressives from schizophrenics by abnormally high Cortisol values. Post-dexamethasone urinary Cortisol as well as combined urinary Cortisol and plasma Cortisol abnormal values gave the best pointers of differentiation. A nonsignificant trend of higher values was observed in bipolar and retarded depressives. Schizophrenics did not differ from normals at any stage.