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Biomedical subjects

D Chandra

Publications and source records attributed to D Chandra.

At least 37 records · Page 2Linked to original sources

Modulation of radioresponse of glyoxalase system by curcumin.

Human beings have been exposed to radiation for many years. It is quite possible that antioxidant phytochemicals consumed in their diet might be providing a variable degree of radioprotection. However, their radiomodifying ability is not well understood. In the present work, curcumin (diferuloyl methane), a phytochemical present in the rhizome of Curcuma longa Linn. has been examined for its radioprotective property using the glyoxalase system which is vital for various biological functions. Curcumin (5, 25 and 50 mg/kg body weight) in olive oil was given orally to Swiss albino male mice (7-8 weeks old) daily for 2 weeks and irradiated with different doses of gamma-radiation (0-6 Gy) at 0.027 Gy per second dose rate on last day of the treatment. The specific activities of glyoxalase I and II were determined in the liver and spleen. The treatment of curcumin prior to irradiation restored the specific activity of glyoxalase system to almost the control level which was suggestive of the radioprotective ability of curcumin. Free radical scavenging and electron/hydrogen donation are probable attributes for the protective effect of curcumin.

Animals↗

Influence of gamma-rays on the mouse liver cytochrome P450 system and its modulation by phenothiazine drugs.

PURPOSE: Phenothiazine drugs have been found to sensitize hypoxic cancer cells while offering protection to normal cells. Since phenothiazines are known to induce the cytochrome P450 system, its radiomodulation by phenothiazines has been examined. MATERIALS AND METHODS: Mice were administered phenothiazines intraperitoneally and irradiated with different doses of gamma-rays at 1.38 Gy/min. The activities of NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase, the content of cytochrome P450 and b5, the extent of lipid peroxidation as well as the activities of LDH, XO, SOD, GST and DTD were determined in the liver. RESULTS: The levels of different components of the cytochrome P450 system and antioxidant enzymes were enhanced up to 5 Gy and decreased thereafter. However, a progressive increase was noticed in peroxidative damage and the activities of LDH and XO. Administration of phenothiazines enhanced the radiation effect on components of the cytochrome P450 system (except NADH-cytochrome b5 reductase) and the activities of SOD, GST and DTD. Concomitantly, phenothiazines inhibited lipid peroxidation, LDH and XO. CONCLUSIONS: Activation of the cytochrome P450 system by phenothiazines leading to the enhancement of antioxidant potential of animals and free-radical scavenging are attributes of the radioprotective action of phenothiazines.

Animals↗

Interaction between N-methyl-D-aspartate receptor antagonists and imipramine in shock-induced depression.

In the past few years, literature has accumulated describing manifestation of seizures following administration of certain antidepressants. Such reports are of particular importance because depression is a frequent psychiatric problem associated with epilepsy. Therefore, in the view of the fact that NMDA receptor antagonists have been reported to reduce behavioural deficits and have been shown to be anticonvulsant, it was considered imperative to study their antidepressant effect using shock-induced depression model in mice. Presentation of inescapable foot shock significantly reduced ambulation and rearing in the open field arena and increased immobility duration in the FST. Pretreatment with imipramine, MK 801 and ketamine significantly prevented the effect of shock. Also, the combination of imipramine with either of the NMDA antagonists antagonised the effect of shock. Haloperidol, prazosin and ketanserin pretreatment modified the effect of these agents. These findings suggest an antidepressant effect of the NMDA receptor antagonists, and a complexity of neurotransmitter mechanisms, which are responsible for the occurrence of behavioural effects in shock-induced depression model.

Animals↗

Cognitive abilities of asphyxiated survivors beyond 5 years of age.

OBJECTIVE: To evaluate the intellectual, psychoeducational and social maturity of a cohort of unimpaired asphyxiated survivors beyond 5 years of age. DESIGN: Case control study on hospital based cohorts on a longitudinal follow up at High Risk and Well Baby Clinics of a teaching hospital. METHODS: The demographic data of these children was recorded. A detailed physical examination was performed. The tests of cognition included the Stanford Binet and the Raven's Progressive matrices. Academic achievement was evaluated by the Wide range achievement test-Revised (WRAT-R). Assessment of visuo-motor integration was done by the Bender Gestalt Test. The proportion of children having soft neurological signs was determined. Vineland Social Maturity Scale was performed on all children. RESULTS: Fifty-four asphyxiated and 57 matched control children participated in the study. Of the 54 asphyxiated children, 27 were tested at a mean age of 7.2 +/- 1.6 years (Group 1) and 27 were tested at a mean age of 10.9 +/- 1.52 years (Group 2). The asphyxiated children as a group performed in the normal range on tests of cognition and academic achievement but were significantly disadvantaged (p < 0.005) as compared to controls. A higher percentage of asphyxiated children had low scores on the Bender Gestalt Test as compared to controls but the difference was not significant. A significantly higher proportion of asphyxiated children of both the groups showed the presence of soft neurological signs as compared to controls. Approximately 11% of the asphyxiated children performed in the abnormal range in the Vineland Social Maturity Scale. CONCLUSION: Cognitive abilities of asphyxiated children beyond the age of 5 years are impaired in comparison to controls, emphasizing the need for early detection and referral for special education.

Adolescent↗

Influence of methylglyoxal on antioxidant enzymes and oxidative damage.

The effect of different doses of methylglyoxal (50-400 mg/kg body wt.) were examined using enzymes involved in the antioxidant function, glutathione (GSH) content and lipid peroxidation in the liver and spleen of Swiss albino mice (7-8 week old) after 6, 12 and 24 h. Significant changes were observed predominantly in the liver. The specific activities of superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase, glyoxalase I (gly I) and glyoxalase II (gly II) were found to decrease in the liver. The mode and magnitude of change in the specific activities was seen to depend on the dose of methylglyoxal and the time after its administration. Methylglyoxal also decreased the GSH content and enhanced the lipid peroxidation in the liver. These findings are suggestive of the adverse effect of methylglyoxal on the antioxidant defence system. It is likely that methylglyoxal undergoes a redox cycle and generates the free radicals which in turn lower the antioxidant status in animals. The increased levels of lipid peroxidation provide support for the involvement of free radical processes in the detrimental effects of methylglyoxal. The response of DT-diaphorase (DTD) seems to be adaptive.

Animals↗

Pharmacotherapeutic education through problem based learning and its impact on cognitive and motivational attitude of Indian students.

OBJECTIVE: The cognitive and motivational attitudes to problem based learning (i.e., simple didactic problem stated in written form and Programmed Patient) has been compared with those to didactic lectures (DL), the traditional teaching method. The change in recall performance measured in MCQ tests was considered as a change in the cognitive domain. The first test was conducted one week after completion of the topic and second test was taken 3 months later, without prior information. The motivational change was recorded by open-ended questions about the learning method. Three groups of students at second MBBS professional year level consisting of 55, 57 and 59 people, were assigned a simple didactic problem stated in written form (SDP), programmed patients (PP), and didactic lecture (DL), respectively. RESULTS: The average scores obtained by the learners in problem based learning (PBL) groups were similar to the students in the DL group in both the tests. Most of the students in PBL groups appreciated the exercise and suggested including more such exercises in the curriculum. These exercises helped them to better understand patient problems and prescribing behaviour as well as in development of communication skills. However, these exercises were time consuming and were not examination oriented. CONCLUSION: Pharmacotherapeutic teaching through PBL could be used within a traditional curriculum to develop relevant and rational use of drugs, provided the evaluation method was also modified.

Association Learning↗

Associated infections in persistent diarrhoea--another perspective.

Seventy-eight children diagnosed as cases of persistent diarrhoea (PD) from 1 month to 5 years of age (mean age 8.92 months) hospitalized during a 2-year study period were screened for the presence of non-gastrointestinal infections. Clinical screening suggested acute respiratory infection (ARI) in 30 per cent cases, urinary tract infection (UTI) in 19 per cent and acute suppurative otitis media (ASOM) in 10 per cent of cases. Investigations revealed pneumonia on chest X-ray (39 per cent), positive urine culture (32 per cent), leucocytosis (31 per cent) and positive blood culture (22 per cent). Seven cases (9 per cent) of pneumonia and 10 cases (13 per cent) diagnosed to have UTI were not identified on clinical screening and could be detected only after investigations. E. coli was the commonest organism isolated from urine culture (23 per cent) and blood culture (14 per cent); 54 per cent of cases had one or the other associated infection and 28 per cent were suffering from more than one infection. Bacterial pathogens were more frequently isolated from blood in children < 6 months (P < 0.01), with vomiting (P < 0.001), and severe malnutrition (P < 0.05); from urine in association with fever (P < 0.001), duration of diarrhoea > 4 weeks (P < 0.05), and vomiting (P < 0.001). Pneumonia was detected on chest radiograph more frequently in children with severe malnutrition (P < 0.001). Sixty eight per cent of cases were successfully treated with dietary management and appropriate treatment of associated infections and 18 per cent of cases died. Mortality was highest in association with sever oral thrush, severe malnutrition, septicaemia, and ARI. Our results suggest that majority of cases of PD are associated with one or the other non-gastrointestinal infections particularly UTI and ARI which may be missed on clinical examination unless efforts are made to investigate these children. Early detection and appropriate management of these infections can considerably modify hospital course and outcome.

Age Distribution↗

Long-term anticonvulsant therapy in tuberculous meningitis--a four-year follow-up.

A treatment protocol for long-term anticonvulsant therapy (ACT) in children with tuberculous meningitis (TBM) has been followed depending upon clinical characteristics and EEG/CT scan findings suggestive of the underlying cause of convulsions. Sixty-three children which included all patients with focal seizures (FS), and those with generalized tonic and clonic seizures (GTCS), and tonic spasms (TS) manifesting more than once during hospitalization and/or associated with abnormal CT/EEG findings were given long-term ACT (Group A). Thirty-eight cases with GTCS before hospitalization, and/or not more than one seizure during first week of hospitalization and without any specific CT/EEG abnormalities (Group B) and 35 cases without any seizures (Group C) did not receive any ACT. Forty-four patients who were finally discharged on long-term ACT, were given phenobarbitone (57 per cent), phenytoin (23 per cent), and a combination of phenobarbitone+phenytoin (14 per cent), and phenobarbitone+sodium valproate (7 per cent). Follow-up was continued for 4 years with 93, 84 and 81 per cent attendance, respectively, in groups A, B and C. Some of the side-effects observed with anti-convulsant drugs included gingival hypertrophy in 11 out of 16 cases (69 per cent) on phenytoin, hyperkinetic behaviour in 3 out of 34 (9 per cent) cases on phenobarbitone, hypocalcaemia in 3 out of 44 cases (7 per cent), hypophosphataemia in 10 out of 44 cases (23 per cent) and increase in alkaline phosphatase in 14 out of 44 cases (32 per cent). CT scan of brain repeated in six cases with multiple tuberculomas showed marked improvement. While 4 out of 41 (10 per cent) cases in group A had recurrence of seizures in the follow-up, only 2 out of 28 cases (7 per cent) in group B presented with GTCS during first 3 months after discharge which was successfully controlled by long-term ACT in later part of the follow-up. Two out of 21 cases (10 per cent) in group C also presented with myoclonic seizures 3 and 5 months after discharge. There was no statistically significant difference in the recurrence/appearance of seizures in the three groups (P = > 0.05). Our results suggest that long-term ACT is not indicated in all cases of TBM with seizures. In view of the known side-effects of anticonvulsant drugs and danger of interaction with antitubercular drugs, it is mandatory to clinically evaluate the patients, identify the cause and restrict long-term ACT only to those cases who are likely to have some abnormal focus resulting in secondary epilepsy. All the cases with FS and some of the patients with GTCS and TS may need to be started on ACT. However, a close follow-up is necessary in all particularly in those for whom ACT has been withheld.

Anticonvulsants↗

Cortisol status in different types of leprosy.

Basal plasma cortisol levels in 12 controls and 60 patients with different types of leprosy were within normal limits. They were significantly lower in multibacillary leprosy patients; this abnormality might be due to long standing stress leading to adrenal exhaustion. The plasma cortisol level significantly increased after the ACTH (Synacthen) stimulation test in all of the varieties of leprosy tested, which suggests that the adrenal reserve is maintained in such cases.

Adrenocorticotropic Hormone↗

Human immunodeficiency virus-1 gp120 and gp160 envelope proteins modulate mesangial cell gelatinolytic activity.

Patients with human immunodeficiency virus (HIV) infection often develop glomerular lesions (mesangial expansion and sclerosis). Modulation of matrix degradation may be important in the expansion of the mesangium. We studied the effect of HIV sera and HIV-1 envelope glycoproteins on gelatinolytic activity of human mesangial cells. HIV serum-treated cells showed lower (P < 0.01) gelatinolytic activity when compared with cells treated with control serum (control serum, 4.3 +/- 0.1 versus HIV serum, 3.3 +/- 0.1 micrograms gelatin degraded/mg protein). Mesangial cells incubated with HIV-1 gp120 protein also showed decreased (P < 0.01) gelatinolytic activity (control, 4.6 +/- 0.2 versus HIV-1 gp120 protein, 1.7 +/- 0.2 micrograms gelatin degraded/mg protein). HIV-1 gp160 protein also inhibited (P < 0.05) mesangial cell gelatinolytic activity as judged by a biotin-avidin assay as well as by a 3H gelatin degradation assay. In contrast, gp alpha-1 acid, a nonviral glycoprotein, did not modulate mesangial cell gelatinolytic activity. These results suggest that the serum contents of HIV patients decrease gelatinolytic activity of mesangial cells. This effect of HIV sera seems to be mediated through HIV-1 gp proteins.

Acquired Immunodeficiency Syndrome↗

Monoclonal antibodies against lactate dehydrogenase of Plasmodium knowlesi.

Lactate dehydrogenase (LDH) of malarial parasites has been demonstrated to be biochemically and immunochemically distinct from the equivalent host enzyme. The polyclonal antibodies raised against the purified plasmodial LDH showed specificity to Plasmodium spp. Six hybridoma cell lines secreting monoclonal antibodies specific to Plasmodium knowlesi LDH have been obtained. The two monoclonal antibodies (2A3B7 and 4A6A7) showed high reactivity with LDH from simian (P. knowlesi. P. cynomolgi), human (P. falciparum, P. vivax) and rodent (P. berghei, P. yoelii) malarial parasites and did not cross-react with red cell LDH as well as with isoenzymic forms of mammalian LDH (A4, B4 and C4). One monoclonal antibody (4A6A7) strongly inhibited the enzyme activity specifically of plasmodial LDH and did not have any effect on the activity of red cell LDH. The other monoclonal (2A3B7) did not show inhibitory effect on parasite LDH. These findings as well as competitive immunoassay studies suggest the presence of at least two parasite specific epitopes on plasmodial LDH.

Animals↗

Morphine stimulates superoxide formation by glomerular mesangial cells.

Focal glomerulosclerosis is the predominant glomerular lesion in heroin addicts. We studied whether morphine, a metabolite of heroin, could directly affect the formation of superoxide by glomerular mesangial cells. Mesangial cells preincubated with morphine (10(-8) M) showed a higher (P < 0.001) production of superoxide when compared to control cells (control) 401 +/- 21 vs. morphine 610 +/- 41 nM/mg protein/h). This effect of morphine on mesangial cells was dose dependent. Naloxone, an opiate antagonist, attenuated morphine-induced formation of superoxide by mesangial cells [control, 317 +/- 4; morphine (10(-8) M), 573 +/- 9; and naloxone (10(-8) M) + morphine (10(-8) M), 333 +/- 6 nM/mg protein/h]. We conclude that morphine enhances formation of superoxide by mesangial cells and this effect of morphine seems to be mediated through opiate receptors. Since superoxide has been demonstrated to cause mesangiolysis, we propose that morphine may be playing a role in the induction of mesangial injury in patients with opiate abuse.

Animals↗

Weightage of formative examinations in certifying examination of pharmacology: an opinion poll and relative performance of learners.

A study was carried out to obtain the view points of 186 graduate students regarding formative examination, it's frequency, weightage in certifying examination, feedback about progress made or lack of it and the planning of learning activities. Majority of students were of the opinion that the class tests and tutorials should be conducted frequently and sufficient weightage of formative examinations should be given in the certifying examination. They were able to get feed back and plan out the learning activities accordingly. The performance in both theory and practicals of formative and certifying examinations in Pharmacology was analyzed. The average percentage marks secured by the students in both theory and practical of the certifying examination were higher than those secured in the formative examination. However, the reliability of theory examinations was more than the practical examinations. A positive correlation was observed between the marks of formative and certifying examination between theory as well as of practicals. The Pearson's Correlation Coefficient gamma was +0.932 and +0.715 while Spearman's rank order Coefficient rho was +0.792 and +0.649 for theory and practicals respectively suggesting positive and strong correlation.

Attitude↗

Pharmacokinetics of aspirin in aged Indians.

The pharmacokinetics of aspirin (ASA) has been studied in elderly Indians (greater than 60 y) of either sex, composing, apparently healthy subjects controlled hypertensives and NIDDM diabetics, in comparison with healthy young subjects. Serum salicylate levels were estimated a 0, 0.5, 1, 2, 4 & 8 h after ASA. The pharmacokinetics of serum salicylate were not changed in elderly subjects as compared to the young after the first dose or after one week of ASA therapy, although greater variability was observed in the elderly. Various laboratory investigations were unaltered after one week in all the groups, except that one elderly hypertensive patient gained weight, and a young subject showed an increase in SGOT & SGPT.

Adult↗