PubMed Health⌕ Search

Biomedical subjects

R Ranjan

Publications and source records attributed to R Ranjan.

50 records · Page 3Linked to original sources

Stimulatory effects of L-5-hydroxytryptophan on postdexamethasone beta-endorphin levels in major depression.

Recently it has been shown that acute administration of 200 mg L-5-hydroxytryptophan (L-5-HTP) PO may increase post-dexamethasone (DST) adrenocorticotropic hormone (ACTH) and cortisol levels in major, but not minor, depressed subjects. This study aimed to examine the effects of 200 mg L-5-HTP PO on post-DST beta-endorphin levels in the same depressed subjects. It was found that in major, but not minor, depressed subjects, L-5-HTP significantly increased post-DST beta-endorphin concentrations as compared to placebo. The L-5-HTP-induced post-DST beta-endorphin responses were significantly higher in major than in minor depressed subjects. There was a significant and positive relationship between L-5-HTP-induced post-DST beta-endorphin and ACTH or cortisol responses. There was a significant and positive relationship between L-5-HTP-induced post-DST beta-endorphin values and the Hamilton Depression Rating Scale (HDRS) score. The results show that the acute administration of L-5-HTP may increase the escape of beta-endorphin secretion from suppression by dexamethasone in major, but not minor, depression.

Adult↗

Lower plasma CC16, a natural anti-inflammatory protein, and increased plasma interleukin-1 receptor antagonist in schizophrenia: effects of antipsychotic drugs.

Recently, it was suggested that in vivo activation of the monocytic and T-lymphocytic arms of cell-mediated immunity (CMI) may occur in schizophrenia and that antipsychotic drugs may modify CMI. The aim of the present study was to examine plasma soluble interleukin-2 receptor (sIL-2R), soluble suppressor/cytotoxic antigen (sCD8), interleukin-1 receptor antagonist (IL-1RA), and Clara cell protein (CC16) concentrations in normal controls, nonmedicated schizophrenic patients, and schizophrenic patients treated with risperidone or loxapine. Plasma concentrations of IL-1RA were significantly higher in nonmedicated schizophrenic patients than in normal controls. Plasma CC16 was significantly lower in nonmedicated and loxapine-treated schizophrenic patients than in normal controls, whereas risperidone-treated patients had plasma CC16 levels which were not significantly different from normal controls. Plasma CC16 levels were significantly and positively related to age at onset of schizophrenia. Plasma sIL-2R was significantly higher in schizophrenic patients who were treated with risperidone than in normal controls and nonmedicated schizophrenic patients. The results show that (i) schizophrenia is accompanied by an activation of the monocytic arm of CMI (i.e., increased plasma IL-1RA) and lower plasma levels of a natural anti-inflammatory and immunosuppressive agent, i.e. CC16, and that the latter may constitute a trait market of schizophrenia; and that (ii) chronic treatment with atypical antipsychotic agents, i.e., risperidone, may normalize lower plasma CC16 and increase plasma sIL-2R.

Adult↗

Depth asymmetries of the pore-lining segments of the Na+ channel revealed by cysteine mutagenesis.

We used serial cysteine mutagenesis to study the structure of the outer vestibule and selectivity region of the voltage-gated Na channel. The voltage dependence of Cd(2+) block enabled us to determine the locations within the electrical field of cysteine-substituted mutants in the P segments of all four domains. The fractional electrical distances of the substituted cysteines were compared with the differential sensitivity to modification by sulfhydryl-specific modifying reagents. These experiments indicate that the P segment of domain II is external, while the domain IV P segment is displaced internally, compared with the first and third domain P segments. Sulfhydryls with a steep voltage dependence for Cd(2+) block produced changes in monovalent cation selectivity; these included substitutions at the presumed selectivity filter, as well as residues in the domain IV P segment not previously recognized as determinants of selectivity. A new structural model is presented in which each of the P segments contribute unique loops that penetrate the membrane to varying depths to form the channel pore.

Amino Acid Sequence↗

Alterations in plasma dipeptidyl peptidase IV enzyme activity in depression and schizophrenia: effects of antidepressants and antipsychotic drugs.

Recently, our laboratory reported that the activity of dipeptidyl-peptidase IV (DPP IV) was significantly lower in the peripheral blood of major depressed patients than in normal controls. The present study examines plasma DPP IV activity in 43 major depressed and 13 schizophrenic subjects versus 21 normal controls and the effects of antidepressants and antipsychotic drugs on plasma DPP IV activity. DPP IV activity was significantly lower in major depressed subjects than in normal controls and schizophrenic subjects. There was a trend towards higher DPP IV activity in schizophrenic patients than in normal controls. There were no significant effects of antidepressants or neuroleptics on plasma DPP IV activity in depressed and schizophrenic patients, respectively. There were no significant relationships between plasma DPP IV activity and plasma cortisol or immune-inflammatory markers, such as serum interleukin-6 (IL-6) or soluble IL-2 receptor. A significant and positive correlation was found between plasma DPP IV and prolyl endopeptidase (PEP) enzyme activity in the study group as a whole and in schizophrenic subjects. The results support the hypothesis that lower and higher plasma DPP IV activities are trait markers of major depression and schizophrenia, respectively. It is concluded that alterations in the enzyme activity of peptidases, such as DPP IV and PEP, play a role in the pathophysiology of major depression and schizophrenia.

Adult↗

Increased serum interleukin-1-receptor-antagonist concentrations in major depression.

Recently, it has been shown that major depression may be accompanied by an increased production of interleukin-1 beta (IL-1 beta), an acute phase (AP) response and simultaneous signs of activation and suppression of cell-mediated immunity. The interleukin-1-receptor antagonist (IL-1-rA) is released in vivo during an AP response and serum levels are increased in many immune disorders. The release of IL-1-rA may limit the pro-inflammatory effects of IL-1. This study has been carried out to examine serum IL-1-Ra in 68 depressed subjects (21 minor, 25 simple major and 22 melancholic subjects) vs. 22 normal controls. Depressed subjects showed significantly higher serum IL-1-rA concentrations than healthy controls. 29% of all depressed subjects had serum IL-1-rA levels higher than the mean value +2 standard deviations of normal controls; 44% depressed subjects had IL-1-rA values greater than 0.215 ng/ml with a specificity of 90%. In depressed subjects, there was a significant and positive relationship between serum IL-1-rA and severity of illness. In depression, there were no significant relationships between serum IL-1-rA concentrations and indicants of hypothalamic-pituitary-adrenal (HPA)-axis activity, such as 24-h urinary cortisol and postdexamethasone cortisol values. Women had significantly higher serum IL-1-rA levels than men. The findings support the thesis that depression is accompanied by an immune-inflammatory response.

Acute-Phase Reaction↗

Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression.

Recently, it was found that major depression may be accompanied by significant changes in cell-mediated and humoral immunity. The purpose of this study was to investigate the plasma concentrations of interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), sIL-2R and transferrin receptor (TfR) in patients with major depression in an acute phase of illness, in remission and during antidepressive treatment. Plasma concentrations of IL-6, sIL-6R, sIL-2R and TfR were significantly higher in major depressed subjects than in healthy controls. In major depressed subjects, but not in normal controls, there were significant positive correlations between the plasma concentrations of IL-6 and sIL-6R, IL-6 and sIL-2R, IL-6 and TfR, and between sIL-2R and TfR. Subchronic treatment with antidepressive drugs, such as fluoxetine or tricyclic antidepressants, did not significantly affect plasma IL-6, sIL-6R, sIL-2R or TfR. The latter did not significantly differ between major depressed patients in an acute phase of illness or in complete clinical remission. It is suggested that: (1) a coordinated and upregulated production of IL-6, sIL-6R, sIL-2R and TfR may constitute a trait marker of major depression; and that (2) an upregulated production of IL-6 may represent a contributing factor to the various immune disorders encountered in major depression and maybe to the pathophysiology or pathogenesis of that illness.

Adult↗

Components of biological variation in plasma haptoglobin: relationships to plasma fibrinogen and immune variables, including interleukin-6 and its receptor.

We investigated the components of biological variation, including seasonality, in plasma haptoglobin (Hp) levels and the relationships between plasma Hp and interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6), sIL-2R, fibrinogen (Fb) and absolute number of peripheral blood mononuclear cells, such as leukocytes, neutrophils, monocytes, lymphocytes, CD4+, CD8+, CD25+ T cells and CD20+ B cells. Monthly blood samples were taken from 26 normal volunteers during one calendar year. The estimated inter- and intra-individual C.V. values for plasma Hp were 27.9% and 20.0%, respectively; the index of individuality was 0.72. No significant seasonal rhythms could be detected in plasma Hp levels. The yearly mean values in plasma Hp were significantly and positively related to those in plasma Fb, absolute number of leukocytes, neutrophils, CD4+ T cells and the CD4+/CD8+ T cell ratio. 49.0% of the variance in the yearly mean values of plasma Hp could be explained by variances in serum IL-6 and number of CD4+ (positively related) and CD8+ (negatively related) T cells. There were significant and positive time relationships between plasma Hp, on the one hand, and plasma Fb, sIL-6R, sIL-2R and number of leukocytes, neutrophils and monocytes, on the other. A smaller part of the within-subject variability in plasma Hp (i.e. 6.0%) could be explained by serum sIL-6R and sIL-2R. It is concluded that there are (1) important between-subject differences in the homeostatic setpoints of plasma Hp, which are related to those in plasma Fb and in immune status and (2) significant within-subject, time relationships between plasma Hp and indicators of immune activation and plasma Fb.

Adult↗

Model-based analysis of the ECG during early stages of ventricular fibrillation.

During the early stages of ventricular fibrillation (VF), identification of the changes in electrocardiographic (ECG) characteristics may be helpful in the determination of defibrillation energy for implantable defibrillators. The hypothesis that the ECG can be quantified by using autoregressive (AR) modeling during VF was tested. Electrocardiograms were recorded for durations of up to 60 seconds of VF in five isolated rabbit hearts. Fourth-order AR parameters of successive 2-second epochs with 50% overlapping of data segments were estimated. At the beginning of VF, mean values of frequency of the first and second poles were 12.5 +/- 1.2 Hz and 24.7 +/- 1.9 Hz, respectively. During VF, frequencies of these poles decreased. At the end of 60 seconds, pole frequencies were 8.7 +/- 1.1 Hz and 21.4 +/- 0.8 Hz. Intersubject variability of the frequencies of the poles was found to be low. Maximum standard deviations for the frequencies of the first and second poles were determined to be 1.9 and 2, respectively. Results of this study show that the VF ECG can be modeled by using the AR modeling technique, and it is possible to quantify the changes in the frequency content of the ECG during VF by using this modeling method.

Action Potentials↗

Recent advances in the pharmacotherapy of schizophrenia.

The major advance in the psychopharmacology of schizophrenia has been the rediscovery of clozapine and the development of other novel antipsychotic drugs, all of which are superior to typical neuroleptic drugs with regard to extrapyramidal symptoms. Clozapine, the best studied of these agents, is also superior in efficacy with regard to psychopathology and cognitive function and has been shown not to cause tardive dyskinesia. A variety of other novel agents, e.g., risperidone, olanazpine, amperozide, seroquel, sertindole, zaprisidone and melperone, must be further studied to establish their efficacy relative to clozapine or the typical neuroleptics, or both. It is likely that these novel agents will displace the typical neuroleptic drugs as the primary treatment of schizophrenia.

Adult↗

Electrical stimulation of cardiac myocytes.

The influence of nonuniform cell shape and field orientation on the field stimulation thresholds of cardiac myocytes was studied both experimentally and computationally. The percent change in excitation threshold, which was studied with patch clamp technique, was found to be 182 +/- 83.1% (mean +/- SD) higher when the electric field (EF) was parallel to the transverse cell axis versus the longitudinal axis (p < 0.0006). On reversing the polarity of the applied EF, the percentage change in threshold was observed to increase by 98.9 +/- 71.0% (p < 0.0002), implying asymmetry of the stimulation threshold of isolated myocytes. Finite element models were made to investigate the distribution of the transmembrane potential of these experimentally studied myocytes. A typical cell model showed that the maximum transmembrane potential induced on opposite ends of the cell was 39.1 mV and -46.5 mV for longitudinal field (aligned with the long axis of the cell), but was 40.5 mV and -44.8 mV for transverse field (aligned with the short axis of the cell). More significantly, it was found that the maximum transmembrane potential occurred at discrete points or "hot spots" on the cell membrane. It is hypothesized that the depolarization of the cell initiates at the hot spot and then spreads over the entire cell. The different excitation thresholds for different polarities of the applied EF can be explained by the different maximum induced at the opposite ends of the cell.

Action Potentials↗

Oesophageal manometry in noncardiac chest pain.

Chest pain of oesophageal origin is an important differential diagnosis in patients with cardiac chest pain. A preliminary survey of 40 patients with noncardiac chest pain (NCCP) revealed oesophageal motility disorder in 47.5%; achalasia cardia being the most frequent disease (47.3%). 15.8% of these patients with motility disorder had features of progressive systemic sclerosis and another 15.8% had non specific oesophageal motility disorder (variants). Compared to barium swallow, oesophageal manometry was found to be superior in the diagnosis of oesophageal motility disorder.

Adult↗