Camphor burns to the palm: an unusual self-inflicted burn.
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Adult↗
Biomedical subjects
S Balakrishnan
Publications and source records attributed to S Balakrishnan.
Micronuclei and cell proliferation as early biological markers of ortho-phenylphenol-induced changes in the bladder of male F344 rats.
ortho-Phenylphenol (OPP) and its sodium salt, sodium ortho-phenylphenate (SOPP), are widely used fungicides and antibacterial agents known to cause tumors in the bladders of male F344 rats. Previous studies in our laboratory have shown that micronuclei and cell proliferation were induced in the bladders of treated rats by a high dose of OPP. In our present studies, we investigated the relationship in dose response between these two biomarkers and previously reported tumor formation in the bladders of male F344 rats. Significant non-linear increases in micronuclei (MN) and BrdU-labeling were seen in the bladder cells of rats treated with the 8000 and 12,500 ppm doses of OPP and at 20,000 ppm SOPP. CREST anti-kinetochore staining showed that the micronuclei originated from both chromosomal loss and breakage. In addition, increases in MN were detected in the bladder but not in the bone marrow, underscoring the value of assessing genotoxicity in the target organ. In summary, these studies clearly show that at high doses, OPP and SOPP are genotoxic to the rat bladder. These results also indicate that micronucleus formation and cell proliferation can detect early OPP-induced changes in the rat bladder and may be useful as biomarkers for bladder carcinogens.
Agrochemicals↗
Force-frequency relation in frog-ventricle is dependent on the direction of sodium/calcium exchange in diastole.
AIM: Force of contraction increases with stimulus-frequency in mammalian and amphibian hearts under control conditions. Here, we have analysed the mechanism of the force-frequency relation (FFR) in frog-ventricle. METHODS: Circular strips of frog-ventricle were subjected to field-stimulation with frequencies in the range 0.03-0.2 Hz and force recorded on a chart-recorder. In another protocol, varying rest-periods were imposed while the preparation beat steadily at 0.2 Hz and the effect of rest on post-rest beat amplitude was noted. RESULTS: Under control conditions, a positive FFR and a rest-induced decay of contraction amplitude (RID) were seen in the frequency range 0.03-0.2 Hz. With cadmium, nifedipine, nickel (40 micromol L(-1)), ryanodine and adrenaline (all drugs at 10 micromol L(-1) concentration, except nickel), the positive FFR and RID seen under control conditions persisted. When the bathing solution contained ouabain (10 micromol L(-1)) or low external sodium (40 mmol L(-1)), or high external calcium (5 mmol L(-1)), the FFR turned negative in the frequency range stated above and there were rest-induced potentiations (RIP). CONCLUSION: When the conditions favour a net leak of calcium in diastole from intracellular stores via the calcium-extrusive mode of sodium-calcium exchanger (NCX), FFR is positive. An increase in frequency lessens the diastolic interval and therefore the diastolic calcium leak, thereby augmenting force. On the other hand, interventions which favour the calcium-acquisitive mode of NCX during diastole, changed the pattern of RID to RIP and converted FFR from positive to negative. With net diastolic calcium uptake, there is better store-filling and therefore higher force at lower frequencies.
Animals↗
Evaluation of hyperdiploidy in the bladder epithelial cells of male F344 rats treated with ortho-phenylphenol.
Ortho-phenylphenol (OPP) is a broad-spectrum fungicide and anti-bacterial agent that has been shown to cause bladder cancer in male F344 rats. An earlier study to investigate the potential role of aneuploidy in OPP-induced bladder carcinogenicity, failed to detect increases in frequencies of hyperdiploidy/polyploidy in treated animals, presumably due to the presence of polyploid cells in the bladder. To overcome this problem, we utilized a novel approach to determine increases in numerical alterations in the slowly dividing replicating cells of the rat bladder following treatment with OPP. Collagenase digestion of the bladder was used to enrich for actively-dividing cells and FISH in conjunction with BrdU was employed to detect hyperdiploidy in the replicating interphase cells. Initial studies were performed using FISH with a chromosome 4 probe. Follow-up studies were conducted with OPP and a positive control, vinblastine sulfate using probes for chromosomes 4 and 19. No significant increases in hyperdiploidy/polyploidy were seen in the replicating bladder cells of the OPP-treated rats using FISH with either the chromosome 4 or 19 probes. As expected, no significant increases in hyperdiploidy were seen in the non-replicating cells. In contrast, highly significant increases in hyperdiploidy/polyploidy, as detected using FISH with probes for either chromosome 4 or 19, were seen in the replicating cells from rats treated with a combination of OPP and vinblastine. The inability to detect increases in hyperdiploidy/polyploidy in the bladder of OPP-treated rats indicates that chromosome gain is unlikely to play a major role in the early genotoxic effects of OPP. However, the increase in hyperdiploidy/polyploidy induced by vinblastine sulfate in OPP-treated rats, clearly demonstrates that this approach using FISH in combination with BrdU is capable of detecting changes in chromosome number even in slowly-dividing tissues, such as the urinary bladder.
Animals↗
Enhancing the in vitro and in vivo detection of aneuploidy by fluorescence in situ hybridization with the use of bromodeoxyuridine as a proliferation marker.
Aneuploidy is associated with spontaneous abortions, birth defects, and many types of human cancers. Currently there are few assays developed for the efficient detection of aneuploidy in vivo. However, with the recent availability of chromosome-specific DNA probes for the rat, fluorescence in situ hybridization (FISH) techniques could be used for the rapid and sensitive detection of aneuploidy in different tissue and cell types. In order to develop a system that can detect alterations in chromosome number in rat cells in vitro, we treated cultured rat lymphocytes with three aneugens-noscapine hydrochloride (0-150 microM) and vincristine and vinblastine sulfate (0-0.06 microM). 5-Bromo-2-deoxyuridine (BrdU; 1 microM) was added to the culture medium to allow proliferating and non-proliferating cells to be distinguished. To test this assay under in vivo conditions, 21-day-old male Sprague-Dawley rats were subcutaneously implanted with osmotic pumps that delivered BrdU (approximately 12 mg/kg per day) continuously. These rats were administered vinblastine sulfate (0, 0.5 and 1mg/kg) by intraperitoneal injection. The rat lymphocytes and hepatocytes incorporating BrdU were detected by immuno-fluorescent labeling, and FISH with a rat chromosome 4 probe was performed on the labeled and unlabeled cells. Highly significant increases in hyperdiploidy were seen in the replicating rat lymphocytes treated with noscapine, vincristine or vinblastine in vitro and in the rat hepatocytes treated with vinblastine in vivo. In contrast, no significant increase in hyperdiploidy was observed in the non-replicating cells. These results demonstrate that this BrdU-enhanced FISH assay with chromosome-specific rat probes can be used to efficiently detect numerical chromosomal aberrations in vitro and in vivo in slowly or moderately replicating rat tissues. The combination of BrdU-labeling and FISH allows the scoring of hyperdiploidy to be focused on the actively replicating cells, thereby increasing the sensitivity of the FISH technique.
Aneuploidy↗
Detection of micronuclei, cell proliferation and hyperdiploidy in bladder epithelial cells of rats treated with o-phenylphenol.
o-Phenylphenol (OPP), a widely used fungicide and antibacterial agent, has been considered to be among the top 10 home and garden pesticides used in the USA. Earlier studies have consistently shown that the sodium salt of OPP (SOPP) causes bladder cancer in male Fischer 344 (F344) rats, whereas OPP has produced variable results. This difference has been attributed to the presence of the sodium salt. To determine cellular and genetic alterations in the rat bladder and the influence of the sodium salt, F344 rats were administered 2% OPP, 2% NaCl and 2% NaCl + 2% OPP in their diet for 14 days. Twenty-four hours before being killed the animals were administered 5-bromo-2'-deoxyuridine (BrdU) by i.p. injection. Bladder cells were isolated, stained with DAPI and scored for the presence of micronuclei and incorporation of BrdU into replicating cells. To determine changes in chromosome number, we used fluorescence in situ hybridization (FISH) with a DNA probe for rat chromosome 4. Significant increases in the frequency of micronuclei and BrdU incorporation were seen in bladder cells of rats from all treatment groups. In contrast, the frequency of hyperdiploidy/polyploidy in treated animals was not increased over that seen in controls. A high control frequency of cells with three or more hybridization signals was seen, probably due to the presence of polyploid cells in the bladder. The presence of polyploid cells combined with cytotoxicity and compensatory cell proliferation makes it difficult to determine whether OPP is capable of inducing aneuploidy in the rat urothelium. In summary, these studies show that OPP can cause cellular and chromosomal alterations in rat bladder cells in the absence of the sodium salt. These results also indicate that at high concentrations the sodium salt can enhance chromosomal damage in the rat urothelium.
Aneuploidy↗
Lipoatrophic diabetes and end-stage liver disease secondary to nonalcoholic steatohepatitis with recurrence after liver transplantation.
BACKGROUND: Lipoatrophic diabetes is an insulin resistance syndrome characterized by the complete or partial lack of adipose tissue and disturbances in lipid and glucose metabolism. Nonalcoholic steatohepatitis (NASH) is a well-described change in liver pathology consisting of steatosis, hepatitis, and fibrosis that can be associated with lipoatrophic diabetes. RESULTS: This article describes the first reported case of lipoatrophic diabetes with NASH leading to liver failure and liver transplantation. Before transplantation, the patient required 600-700 U of insulin/day. After transplantation, a dramatic decline in her insulin requirements was observed, despite corticosteroids. Eighteen months after transplantation, her glycemic control worsened, and she developed recurrent NASH on serial liver biopsies. CONCLUSIONS: NASH associated with lipoatrophic diabetes can recur after liver transplantation, and in this case, was accompanied by increased insulin requirements. These results suggest that the development of NASH itself may contribute to the insulin resistance observed in lipoatrophic diabetes.
Adult↗
An audit of the use of antirheumatic drugs in a north Indian referral hospital.
OBJECTIVE: This study was conducted with the aim of auditing the pattern of use of antirheumatic drugs in a tertiary care hospital in Northern India. METHODS: The study was carried out in 1000 patients recruited sequentially from the clinic for a period of 1 year (January to December 1999). Patient data such as age, sex, income, family size, diagnosis, duration of illness, drugs prescribed/duration, adverse drug reaction were noted and used to calculate core drug use indicators and pattern of drug use. RESULTS: The pattern of drug use was in accordance with the standard practices followed internationally. In rheumatoid arthritis the most common prescriptions were for non-steroidal antiinflammatory drugs (NSAIDs) alone, followed by the combination of NSAIDs, disease modifying agents (DMARDs) and steroids. Of the NSAIDs diclofenac was the most frequently prescribed drug, while chloroquine was the most commonly used DMARD. The most commonly seen adverse drug reactions were gastritis, Cushings syndrome and decreased visual acuity. CONCLUSION: In conclusion, this study has demonstrated that in this clinic, the pattern of use of antirheumatic drugs follows standard guidelines.
Adult↗
Anticonvulsant activity of omeprazole in rats.
Omeprazole has long been used as an effective agent to treat peptic ulcer. Recent studies have shown that in addition to inhibiting the H(+)-K(+)ATPase, it also inhibits carbonic anhydrase (CA) types I, II and IV. This led us to investigate its anticonvulsant effect in a rat model of electroconvulsion. Since other carbonic anhydrase inhibitors like acetazolamide induce tolerance upon repeated use, we tested the tolerance potential of omeprazole upon repeated administration of up to 1 week. The animals were divided into four groups receiving normal saline, omeprazole 0.5, 1 or 2 mg/kg intraperitoneally. CC(50), i.e. the threshold current inducing tonic hind limb extension in 50% of the rats was established using a technoconvulsometer which delivers currents of varying intensity via ear clip electrodes. The CC(50) was established 30 min after injection of omeprazole. In another group of rats, omeprazole 2 mg/kg was given for 6 days and the CC(50) determined on days 0, 1, 3 and 6. Also the concentration of omeprazole in the brain was determined using high performance liquid chromatography. The CC(50) in vehicle-treated rats was 98 mA, which increased to 126, 135 and 162 mA with 0.5, 1 and 2 mg/kg of omeprazole, respectively. On repeat-dose studies the CC(50) on day 0 was 96 mA, on day 1 166 mA, on day 3 129 mA and on day 6 102 mA. The average brain concentration of omeprazole was 53.2+/-6.9 ng/g of brain tissue. In conclusion, this study has shown omeprazole to be an effective anticonvulsant, but rapidly develops tolerance to its anticonvulsant action. This study can stimulate interest in the development of agents with dual function -- inhibition of CA as well as the accompanying Na(+)-K(+) ATPase -- and such agents may prove to be effective anticonvulsants without exhibiting tolerance.
Animals↗
A randomized parallel trial of topical aspirin-moisturizer solution vs. oral aspirin for acute herpetic neuralgia.
BACKGROUND: In this study, the efficacy of oral aspirin vs. topical aspirin in moisturizer (Vaseline Intensive Care Lotion) was studied in an open, randomized, parallel trial in patients with acute herpetic neuralgia. METHODS: Thirty patients were evaluated in the trial, with 15 in each group. The patients were randomized to receive either oral aspirin, 375-750 mg three times a day, or 75 mg topical aspirin/mL of moisturizer (5-10 mL, depending on the extent of involvement), three times a day, for 21 days. Pain was assessed daily by means of a self-rating visual analog scale and physician assessment. In addition, the skin and plasma levels of aspirin were measured in both groups. RESULTS: The mean time to onset of pain relief was 44 min with topical aspirin and 110 min with oral aspirin. The mean duration of pain relief after a single application of topical aspirin was 5.4 h, whereas it was 3.5 h with oral aspirin. The mean visual analog scale scores for pain with oral aspirin decreased from 68.2 +/- 6.1 on day zero to 43.1 +/- 8.7 on day 21, which was not significant compared with the baseline score. With topical aspirin, the baseline pain score was 77.5 +/- 3.7 and decreased to 6.8 +/- 3 on day 21 (P < 0.001 compared to the baseline score and compared to oral aspirin). The mean plasma and skin levels of aspirin following oral administration were 16.21 +/- 1.1 microg/mL and 1.97 +/- 0.3 microg/mm2, respectively. After topical administration, the mean plasma level of aspirin was 2.29 +/- 0.5 microg/mL (P < 0.01 vs. oral aspirin) and the skin level was 5.96 +/- 0.4 microg/mm2 (P < 0.05 vs. oral aspirin). Treatment tolerance was excellent in both groups. CONCLUSIONS: This trial has demonstrated that topical aspirin in moisturizer is clearly superior to oral aspirin in relieving the pain of acute herpetic neuralgia, and that the analgesic activity of aspirin is largely due to its local effect.
Administration, Oral↗
Effect of duration of pilocarpine-induced status epilepticus on subsequent cognitive function in rats.
The aim of this study was to determine the effect of the duration of pilocarpine-induced status epilepticus (SE) on subsequent cognitive function in rats. SE was induced by pilocarpine (320 mg/kg i.p.) and was terminated by injection of 1 mg/kg diazepam at 30, 60 and 90 min in 3 groups of 10 rats each. Cognitive function was tested by a passive avoidance task and was assessed at the baseline and on days 1, 7, 14 and 21 (post SE). It was found that cognitive function was disrupted on days 7, 14 and 21 post SE in rats who had SE for 60 and 90 min, whereas it was not affected in rats that had 30 min of SE. Hence, the duration of SE may affect future cognitive performance and mandates emergency treatment.
Animals↗
Role of nitric oxide in experimental models of psychosis in rats.
The aim of our study was to investigate the effects of the NO precursor L-arginine and the nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NORAG) on amphetamine-induced stereotypy, haloperidol-induced catalepsy and conditioned avoidance response (CAR) in rats. Amphetamine (3 mg/kg i.p.) was used for the induction of stereotypy, while for the induction of catalepsy and CAR, haloperidol (2 mg/kg i.p.) was used. This study was divided into 2 parts--acute administration of L-arginine (150 mg/kg i.p.) and L-NOARG (50 mg/kg i.p.) and chronic administration of L-arginine (150 mg/kg/day i.p.) and L-NOARG (50 mg/kglday i.p.) for 5 days. We found that L-arginine inhibited amphetamine-induced stereotypy and haloperidol-induced catalepsy, but intensified CAR. On the other hand, L-NOARG intensified stereotypy and catalepsy but inhibited CAR. Also, there was no significant difference between the scores of acute and chronic administration of L-arginine and L-NOARG. It is concluded from our study that nitric oxide produces conflicting results on various models of psychosis. L-arginine might be useful as an antipsychotic without causing extrapyramidal symptoms.
Animals↗
Retrospective dosimetry based on cytogenetic study of individuals chronically exposed to ionizing radiation.
Analysis of chromosomal aberrations (CAA) was carried out in 27 radiation workers with cumulative exposures of approximately 500 mSv received over a period of 2-3 decades. A similar study was carried out in 20 age- and gender-matched healthy individuals who served as controls. The average age of the exposed group was 50 years, and that of the controls was 51 years. The absorbed radiation dose was calculated by using the linear component of the in vitro dose response curve established for 60Co gamma-rays. In the controls we found only 3 dicentrics in 5,500 metaphases analyzed. In the exposed group, we detected 49 dicentrics and 1 centric ring in 13,900 metaphases analyzed. Because of the small number of dicentrics scored in each individual, the dose estimates of our method of study suffers from a large statistical uncertainty. The collective dose calculated from our data was 3.4 Sv. The difference in the physical dose based on personal monitoring and that from biological dosimetry may be attributed to the disappearance of lymphocytes carrying the aberrations from the living system. These results are consistent with the present knowledge of the kinetics of turnover of T-lymphocytes. Most residual damage appears to be from the long-lived component of T-lymphocytes with a mean life of 10 years.
Air Pollution, Radioactive↗
Anticonvulsant profile of ondansetron in rats.
Recent studies have shown the involvement of 5-hydroxytryptamine (5HT) in the pathogenesis of epilepsy. Hence it was decided to investigate the effect of the 5HT3 receptor antagonist ondansetron against maximal electroshock (MES)-induced seizures in rats. Also, the anticonvulsant activity of ondansetron in combination with phenytoin and its effect on the cognitive deficits induced by phenytoin were studied. MES was induced through ear-clip electrodes using a current strength of 150 mA for 0.2 second. The index of protection was taken as the inhibition of tonic hindlimb extension. The ED25 and ED16 doses of ondansetron were combined with subanticonvulsant doses of phenytion, i.e., 6 and 3 mg/kg. The retention latencies in the passive avoidance task (PAT) were assessed on Days 1 and 21 of chronic administration of ondansetron alone, phenytoin alone, and ondansetron in combination with phenytoin. The ED50 of ondansetron was found to be 1.05 (0.51-2.2) mg/kg. The combination of ondansetron with phenytoin had a potentiating effect against MES. Also, the retention latencies in the PAT of ondansetron alone and ondansetron in combination with phenytoin were significantly higher than that of phenytoin alone. Thus, ondansetron has potent anticonvulsant activity in rats and further potentiates the anticonvulsant activity of phenytoin. Also, it attenuates the cognitive dysfunction induced by phenytoin and merits further research for its mechanisms.
Journal Article↗
Evidence of functional somatotopy in GPi from results of pallidotomy.
The objective of this study was to explore the functional anatomy of the globus pallidus internus (GPi) by studying the effects of unilateral pallidotomy on parkinsonian 'off' signs and levodopa-induced dyskinesias (LID). We found significant positive correlations between the preoperative levodopa responsiveness of motor signs and the levodopa responsiveness of scores in timed tests (Core Assessment Program for Intracerebral Transplantations) in the contralateral limbs and the improvement in these scores after surgery, whereas there was no correlation with the improvement in LID. We also found a highly significant correlation (P: < 0.0001, r = 0.8) between the volume of the ventral lesion in the GPi and the improvement in LID in the contralateral limbs, whereas there was no correlation between the ventral volume and the improvement in parkinsonian 'off' signs. The volumes of the total lesion cylinder and the dorsal lesion did not correlate with the outcome of either dyskinesias or parkinsonian 'off' signs. The differential predictive value of levodopa responsiveness for the outcome of parkinsonian 'off' signs and LID and the different correlations of ventral lesion volume with dyskinesias and parkinsonian 'off' signs indicate that different anatomical or pathophysiological substrates may be responsible for the generation of parkinsonian 'off' signs and dyskinesias. Whereas cells in a wider area of the GPi may be implicated in parkinsonism, the ventral GPi seems to be crucial for the manifestation of LID. We suggest that our observations are additional proof of the functional somatotopy of the systems within the GPi that mediate parkinsonism and dyskinesias, especially along the dorsoventral trajectory used in pallidotomy. The outcome of pallidotomy in which the lesion involves the ventral and dorsal GPi could be the net effect of alteration in the activity of pathways which mediate different symptoms, and hence could be variable.
Dyskinesia, Drug-Induced↗
Cytogenetic analysis of peripheral blood lymphocytes of occupational workers exposed to low levels of ionising radiation.
The incidence of chromosomal aberrations was analysed in peripheral blood lymphocytes of occupationally exposed people having cumulative doses of 500 mSv. The exposed individuals showed higher frequencies of dicentrics as well as acentrics than normal controls. Absorbed radiation dose was calculated by using in vitro dose response curve established for Cobalt-60 gamma rays. In the control constituting 17 healthy individuals, two dicentrics were detected among 3700 metaphases analysed. In the exposed group 27 dicentrics and one centric ring was detected among 8400 metaphases analysed. Due to small number of dicentrics scored in each individual, the dose estimate suffers from a large statistical uncertainty. The collective dose was found to be 1.89 Gy. This is in good agreement with the corrected physical doses, assuming a mean life of 10 years for the disappearance of lymphocytes. The physical doses accumulated during the last 10 years of occupation were also in good agreement with the biological dose estimate.
Adult↗
Anticonvulsant profile of nimodipine and nitrendipine against pentylenetetrazole induced seizures in rats.
The activity of nimodipine and nitrendipine against pentylenetetrazole (PTZ) induced seizures in Albino rats was studied alone and in combination with valproate. The median effective dose [ED50] of valproate, nimodipine and nitrendipine were initially determined. All the 3 drugs were injected i.p. 30 min before the induction of seizures. Seizures were induced by PTZ 85 mg/kg i.p., and subsequently the effect of combining ED50 doses of nimodipine and nitrendipine with ED50 dose of valproate was evaluated. ED50 of valproate and nitrendipine were 129 and 2.5 mg/kg respectively. ED50 of nimodipine could not be established since a dose-response relationship was not obtained. Hence, for the purpose of combination studies, 4 mg/kg of nimodipine was used. Both nimodipine (4 mg/kg) and nitrendipine (2.5 mg/kg) decreased the ED50 of valproate from 129 to 40 mg/kg. Both nimodipine and nitrendipine potentiate the activity of valproate against PTZ induced seizures and can be considered as potential adjuvant anticonvulsants which merit further study.
Animals↗
Role of nitric oxide in electroshock and pentylenetetrazole seizure threshold in rats.
There are contradictory reports on whether nitric oxide (NO) is a proconvulsant or anticonvulsant. Hence a study was designed to investigate the effect of NO donor l-Arginine and NO synthesis inhibitor N omega-nitro-L-arginine (NOARG) on electroshock- and pentylenetetrazole (PTZ)-induced seizure threshold in rats. L-arginine was tested in three doses (75, 150 and 300 mg/kg), and NOARG was administered in doses of 4, 8 and 16 mg/kg. L-Arginine increased the intensity of current required to produce a threshold seizure, whereas NOARG had the opposite effect. In PTZ-induced seizures, L-arginine significantly decreased the dose of PTZ required to produce a threshold seizure, while NOARG increased it. Hence, it was concluded that NO synthase inhibition had the opposite effect in electroshock- and PTZ-induced seizures, meriting further studies on the mechanism of effect.
Animals↗