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Biomedical subjects

R C Arora

Publications and source records attributed to R C Arora.

At least 55 records · Page 3Linked to original sources

Effect of desipramine treatment on 3H-imipramine binding in the blood platelets of depressed patients.

Platelet imipramine binding (IB) was studied in depressed patients before and after treatment with desipramine for 17-28 days. Administration of desipramine was associated with a significant increase in Bmax. There was a trend for an increase in Kd, but it did not reach statistical significance. The net result of the changes in Bmax and Kd was an increase in IB. There were significant correlations between the change in depression ratings and pretreatment Kd, as well as the change in Kd during treatment. These results suggest that decreased IB is not a trait-dependent marker, but a state-dependent marker for depression.

Adult↗

Seasonal variation of imipramine binding in the blood platelets of normal controls and depressed patients.

Imipramine binding (IB) was studied in the blood platelets from normal controls and depressed patients over a 4-year period (1981-1984) to determine if seasonal variation was present in Bmax or KD. Bimonthly variation in the Bmax of IB was found in normal controls studied longitudinally. No such variation was found when individual values from normal controls were examined on a monthly or seasonal basis. Bmax in depressed patients showed a significant seasonal, but not monthly, variation. KD of IB varied in normal controls using monthly or seasonal data, but not in the probably more reliable bimonthly data. These results suggest that IB studies comparing groups of subjects should match groups for season of the year or, for greater accuracy, month of the year.

Adult↗

Genetic control of serotonin uptake in blood platelets: a twin study.

Platelet serotonin (5HT) uptake was studied in 13 pairs of monozygotic (MZ) twins, 13 pairs of dizygotic (DZ) twins, and 14 pairs of unrelated normal volunteers. Significant intraclass correlations (ICC) in the affinity (Km) of 5HT uptake in the blood platelets of MZ and DZ twins and unrelated pairs were found. However, the ICC for maximum velocity (Vmax) was significant only in MZ and DZ twins. The ICC of the Vmax of 5HT uptake of MZ twins was significantly greater than that of DZ twins and unrelated pairs. This suggests that the Vmax of 5HT uptake in blood platelets is, in part, heritable. Thus, low platelet 5HT uptake (Vmax) in major depression and other disorders may be genetically determined.

Adult↗

Serotonin uptake in blood platelets of Duchenne muscular dystrophy patients.

Serotonin (5-HT) uptake was studied in the blood platelets of 10 patients with Duchenne-type muscular dystrophy (DMD) and 7 age-matched controls. Vmax (maximum number of uptake sites) of platelet 5-HT uptake in the DMD patients was significantly less than that of the normal controls. There was no difference in the affinity for 5-HT (Km) between the two groups. There was a significant negative correlation between serum creatine kinase activity and Km of 5-HT uptake in blood platelets of these patients. However, no correlation was found between Km or Vmax and ambulatory status of DMD.

Adolescent↗

Effect of subchronic treatment with imipramine, chlorpromazine and the combination on 3H-imipramine binding in rat blood platelets and frontal cortex.

The effects of subchronic administration of imipramine (IMIP), chlorpromazine (CPZ) and the combination of IMIP + CPZ on 3H-IMIP binding of rat blood platelets and cortex were studied. All three treatments decreased the number of IMIP binding sites (Bmax) of rat blood platelets and cortex. The combination produced a significantly greater decrease in Bmax in platelets than either treatment alone; a similar trend in cortex was observed. The effect of some neuroleptics on 3H-IMIP binding sites may be relevant to their antidepressant action. These results, together with previous evidence that the combination has a synergistic effect on down regulation of brain serotonin-2 (5-HT2) receptors, suggest that changes in serotonergic neurotransmission may be relevant to the enhanced efficacy of the combination of tricyclic antidepressants and neuroleptics, compared to either type of drug alone, in the treatment of delusional depression.

Analysis of Variance↗

Effect of adrenalectomy and corticosterone on [3H]imipramine binding in rat blood platelets and brain.

The effect of adrenalectomy and administration of glucocorticoids on [3H]imipramine binding (IB) of rat blood platelets and brain was investigated. Adrenalectomy significantly increased both Kd and Bmax of IB in the blood platelets but not the brain of male Sprague-Dawley rats. Administration of corticosterone acetate, 1 mg/kg i.p. for 7 days, decreased both Kd and Bmax in the blood platelets of sham-operated rats, but only Bmax in adrenalectomized rats. Corticosterone administration also decreased Bmax in frontal cortex and hypothalamus of sham and adrenalectomized rats but had no effect on Kd. These results suggest that glucocorticoids may modulate imipramine binding.

Adrenalectomy↗

3H-imipramine binding in blood platelets of schizophrenic patients.

3H-Imipramine binding was studied in the blood platelets of 51 unmedicated chronic schizophrenic patients. Univariate analyses of log-transformed data revealed that Bmax was significantly lower in schizophrenic patients than normal volunteers; Kd was nonsignificantly higher in the schizophrenics. A multivariate analysis of variance indicated the Kd and Bmax both differ significantly between normal controls and schizophrenic patients in the direction of increased Kd and decreased Bmax in the schizophrenics. These results indicate that decreased platelet imipramine binding is not specific for major depression.

Adult↗

Platelet markers of suicidality.

Six serotonergic measures in blood platelets, Km and Vmax of serotonin (5-HT) uptake, Kd and Bmax of 3H-imipramine binding, 5-HT content, and MAO activity, were measured in depressed and other psychiatric patients and related to Hamilton Depression Scale suicide ratings. Km was negatively correlated with the suicide rating while Kd was positively correlated with it. Multivariate analyses showed that Km, Kd, Vmax, and MAO activity were significant predictors of Hamilton Depression Scale suicide ratings. Low platelet MAO activity was present in seven nondepressed females who had made suicide attempts in the current episode. The direction of the association between the platelet measures and suicide ratings indicated diminished presynaptic serotonergic activity in patients with high suicide ratings, if the platelet findings could be extrapolated to 5-HT nerve terminals.

Bipolar Disorder↗

Effect of reduced oxygen intermediates on sarcolemmal muscarinic receptors from canine heart.

The effect of oxygen free radicals generated by xanthine-xanthine oxidase system and hydrogen peroxide were investigated on cardiac muscarinic cholinergic receptors. We have used highly enriched sarcolemmal preparations isolated from canine myocardium. Exposure of the sarcolemma to oxygen free radicals by xanthine-xanthine oxidase system resulted in a significant (P less than 0.05) decrease of Bmax of (3H)-QNB (4.66 +/- 0.51 to 2.68 +/- 0.22 pmoles/mg protein). Addition of superoxide dismutase (SOD) and catalase (10 micrograms/ml) resulted in a significant reversal of Bmax value to 3.72 +/- 0.39 pmoles per mg protein (p less than 0.05). However, the affinity constants of dissociation (KD) were not altered appreciably with the exposure to oxygen free radicals with or without scavengers. Hydrogen peroxide significantly depressed 3H-QNB binding to the receptors in a dose-dependent manner in a concentration range between 4.41 mM -441 mM. This depression was completely inhibited by 10 micrograms/ml catalase. The study demonstrates that the oxygen free radical species are capable of disrupting (3H)-QNB binding to the cardiac muscarinic receptors.

Animals↗

Effect of protein concentration on kinetic constants (Kd and Bmax) of 3H-imipramine binding in blood platelets.

3H-imipramine binding was studied in the blood platelets of 80 normal controls and 50 depressed (psychotic and nonpsychotic) patients. Protein concentration in the incubation mixture, and Kd and Bmax values were correlated in normal controls and depressed patients. A small but significant correlation between protein in the incubation mixture and Bmax was observed in normal controls and depressed patients. There was also a significant correlation between protein and Kd of imipramine binding in the blood platelets of unipolar psychotic depressed patients. However, analysis of covariance to remove the effect of protein on Kd and Bmax did not change the basic finding of decreased Bmax in the blood platelets of psychotic depressed patients.

Adult↗