Biomedical subjects
Publications and source records attributed to S Sudha.
Peripheral gangrene as a manifestation of tuberculosis is very uncommon. An 8 year old male child presented with non-healing ulcer over the sole of left foot, left inguinal tubercular lymphadenopathy with scrofloderma, tubercular pleural effusion and gangrene of the right fore foot. The child improved on antitubercular treatment.
OBJECTIVE: To analyze the pattern of changes in GSTs in cancerous and adjacent non-cancerous tissues obtained from breast cancer patients undergoing surgery. DESIGN AND METHODS: Cytosolic GST purification, assay of GST, protein expression levels, and GST-synaptotagmin association were analyzed using standard biochemical techniques like GSH-affinity purification, spectrophotometry, SDS-PAGE, Western blots, and matrix-assisted laser desorption and ionization-time of flight (MALDI-TOF). RESULTS: GST activity in cancerous tissues (0.26 U/mg protein) was significantly higher (P < 0.05) as compared to those from adjacent non-cancerous tissues (0.14 U/mg protein) of breast cancer patients. Further analysis of GST subunits on SDS-PAGE and Western blots using class-specific GST antibodies revealed significant elevation in GST-pi levels in cancer tissues with no appreciable changes in GST-alpha and GST-mu. Along with the elevation of GST-pi levels, high molecular weight proteins (approximately 70 kDa) cross reacting with GST antibodies were detected only in surgically resected tumor biopsies but not in the non-cancerous tissues adjacent to the tumor. Based on MALDI-TOF analysis, the high molecular weight band was identified as synaptotagmin V bound to GST-M1 with 47% sequence coverage after processing on an MS-FIT search engine. CONCLUSIONS: Our results suggest a novel putative functional role for the GST-synaptotagmin complex in human breast cancers. As this association of GST M1-synaptotagmin was not seen in adjacent non-cancerous tissues, this can be used as a marker for breast cancers.
Explore the source record for details and available documents.
A case of idiopathic hypereosinophilic syndrome who had an unusual presentation in the form of pericardial effusion is being presented here. The child initially responded to corticosteroids but could not maintain normal eosinophil counts on tapering of steroids. Therefore he was put on hydroxyurea and low dose of steroids with regular monitoring of absolute eosinophil counts.
Ten new synthetic thiazolidine-4-ones derivatives (5 chlorothiazolidine-4-ones, 3 methoxythiazolidine-4-ones and 2 hydoxythiazolidine-4-ones) having different substituents at R1, R2 and R3 were evaluated for their analgesic activity using different animal models and their structure activity relationship was also elucidated. Chlorothiazolidine-4-ones and methoxythiazolidine-4-ones exhibited analgesic activity in tail flick test, tail immersion test and acetic acid writhing test. C-III (chloride substituents at R1 and R2) produced higher latencies than any other compounds in tail flick test and C-I (no substituents at R1 and R2) was not effective in acetic acid writhing test. Hydroxythiazolidine-4-ones did not show analgesic activity in any of the animal models used. In conclusion, the character of substituents at R3 of thiazolidine moiety position may have an effect on the analgesic activity of thiazolidine-4-ones and either chloride or methoxy substitution may be necessary to produce analgesic activity. Two chloride substituents in a compound may increase the central analgesic activity of the compound.
Effect of pre-electroconvulsive shock (ECS) administration of calcium channel blockers (CCBs) like verapamil, diltiazem, nifedipine, nimodipine, flunarizine and cinnarizine on retrograde amnesia induced by ECS was examined using passive avoidance paradigm in rats. The groups (Gr 1-7) of adult, male Wistar rats received true ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; ip) and other groups (Gr 8-14) received sham ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; i.p). The anti-amnestic activity of CCBs were evaluated using the passive avoidance paradigm in rats. Results showed that, the baseline latencies for all the groups did not differ significantly. Rats receiving true ECS produced significantly lower latencies. There was increase in the post ECS step through latencies of the rats administered CCBs before ECS. Therefore, pre-ECS administration of calcium channel blockers might reduce retrograde amnesia produced by ECS without altering seizure duration.
BACKGROUND: Electroconvulsive therapy (ECT) stimulus parameters, such as pulse amplitude, pulse width, pulse frequency, and stimulus duration, differently influence seizure threshold and, possibly, other neurobiological effects of ECT. We examined the influence of these parameters on the EEG power spectrum in an animal model. METHODS: Adult, male, Wistar rats (n=54) were randomized to receive one of five differently constituted (approximately) 30-mC electroconvulsive shock (ECS) stimuli administered once on alternate days for a total of three ECS. A single-lead, unipolar EEG recording was obtained before, during, and immediately after each ECS seizure. EEG power was computed in eight frequency bands from 2 to 40 Hz. Greater ictal EEG power, greater postictal EEG suppression, and greater interictal EEG power, especially in lower frequency bands, were a priori defined as proxies of seizure efficacy. RESULTS: Motor and EEG seizure duration and a proxy for seizure generalization did not differ significantly across the five stimulus groups. Despite equivalent charge, the five stimuli varied widely in their effects on the EEG proxies of seizure efficacy. The narrow (0.6 milliseconds) pulse width, high (100 Hz) pulse frequency combination was best associated with EEG proxies of seizure efficacy; with this combination, a longer stimulus train duration appeared superior to a greater pulse amplitude. The wide (2 milliseconds) pulse and low (30 Hz) frequency combination was least associated with EEG proxies of efficacy. Stimulus "on" time, number of pulses delivered, and the rate of delivery of charge were not associated with the EEG proxies; the former finding questions the validity of dosing ECT in units of charge. CONCLUSIONS: These findings suggest a rationale for optimizing stimulus parameter choices during ECT and provide a framework for the evaluation of electrical aspects of the ECT stimulus.
Recent developments in basic research suggest that therapeutic breakthroughs may occur in Alzheimer's disease treatment over the coming decades. To model the potential magnitude and nature of the effect of these advances, historical data from congestive heart failure and Parkinson's disease were used. Projections indicate that therapies which delay disease onset will markedly reduce overall disease prevalence, whereas therapies to treat existing disease will alter the proportion of cases that are mild as opposed to moderate/severe. The public health impact of such changes would likely involve both the amount and type of health services needed. Particularly likely to arise are new forms of outpatient services, such as disease-specific clinics and centers. None of our models predicts less than a threefold rise in the total number of persons with Alzheimer's disease between 2000 and 2050. Therefore, Alzheimer's care is likely to remain a major public health problem during the coming decades.
Adult, male Wistar rats showed substantial left (22.2%) or right (52.8%) bias in spontaneous arm preference in the T-maze; this bias was consistent over 2 days of testing separated by a 30 day interval. Left and right biased rats learnt very rapidly when trained to enter the arm ipsilateral to the bias; learning was significantly poorer or did not occur in the contralateral arm. This contralateral learning difficulty was particularly evident when transfer of learning was assessed. Right-biased rats were more impaired in contralateral learning than left-biased rats. Unbiased rats (25%) also showed learning difficulties. This study has important implications for spatial tasks of learning and memory; with specific reference to the T maze, it is concluded that animals should be preselected for capacity to learn in both arms, randomization into experimental and control groups should be stratified for spontaneous arm bias, and original learning should be directed towards the contralateral arm while transfer of learning, if required, can be directed into the ipsilateral arm.
Previous research found that the administration of verapamil and felodipine immediately before electroconvulsive shocks (ECS) attenuated ECS-induced retrograde amnesia. This study examined whether sodium nitroprusside, an antihypertensive drug that does not affect calcium channels, has a similar action. Adult male Sprague-Dawley rats received nitroprusside (0.5 mg/kg ip) or saline 3 minutes before each of three once-daily true or sham ECS. Retention of pre-ECS learning was studied 1 day after ECS using a passive avoidance task. Nitroprusside was associated with increased seizure duration in ECS-treated rats, and with enhanced recall in both true and sham ECS groups. The latter finding suggests that nitroprusside nonspecifically improves cognitive functions, and does not support the hypothesis that ECS-induced cognitive impairment is a result of blood-brain barrier breach. Nitric oxide mechanisms may underlie the benefits purveyed by nitroprusside.
Phenylephrine is a nonselective alpha-receptor agonist. This study examined whether the administration of phenylephrine immediately before electroconvulsive shocks (ECS) attenuated ECS-induced retrograde amnesia. Adult male Wistar rats received phenylephrine (0.25 mg/kg i.p.) or saline 3 min before each of three once-daily true or sham ECS. Retention of pre-ECS learning was studied 1 day after the ECS course using a passive avoidance task. Phenylephrine increased seizure duration in ECS-treated rats, and also enhanced recall in both true and sham ECS groups. The latter finding suggests that phenylephrine nonspecifically improves cognitive functions, perhaps through adrenergic mechanisms that improve memory consolidation and storage. Since phenylephrine increases blood pressure, its cognitive effects also weaken the hypothesis that ECT-induced cognitive impairment results from the seizure-related hypertensive surge.
Hypo- and hyper-corticosteronisms have adverse effects on ovarian endocrine and exocrine functions. In the present study, the mechanism by which corticosterone in excess or insufficiency impairs steroidogenesis in granulosa and thecal cells was investigated in adult albino Wistar rats. In this regard, rats were administered with corticosterone-21-acetate (2 mg/100 g b.wt., s.c., twice daily) or metyrapone (11beta-hydroxylase blocker) (10 mg/100 g b.wt., s.c., twice daily) for 15 days and a group of corticosterone/metyrapone treated rats was withdrawn of treatment and maintained for another 15 days and killed during their diestrus phase. Administration of corticosterone-21-acetate while elevated the serum corticosterone levels, metyrapone diminished the same. Administration of metyrapone reduced the serum levels of LH and estradiol; corticosterone reduced the levels of FSH in addition to LH and estradiol. In vitro production of progesterone and estradiol by the granulosa and thecal cells was decreased due to altered corticosterone status. Whereas administration of corticosterone significantly reduced the activity of 3beta-hydroxysteroid dehydrogenases (3beta-HSD) in granulosa and thecal cells, it reduced the activity of 17beta-HSD only in granulosa cells. While metyrapone treatment reduced the activity of 17beta-HSD in granulosa as well as thecal cells, it reduced the activity of 3beta-HSD only in thecal cells. The findings of the present investigation clearly demonstrate that excess or insufficiency in corticosterone affects steroidogenic process in the ovary. This is achieved by decreasing the levels of gonadotropins probably by their diminished synthesis and secretion and by interfering at the signal transduction process of these gonadotropins.
Effects of streptozotocin (STZ)-diabetes and insulin treatment on the functioning of pituitary-testicular axis during sexual maturation was studied. Prepubertal (30 days old) and pubertal (50 days old) male Wistar rats were made diabetic by a single injection of STZ. A group of diabetic rats was given insulin (3U/100 g b.wt./day in 2 equally divided doses), 3 days after STZ treatment. Prepubertal and pubertal rats of all groups were killed on postnatal days 51 and 71, respectively. STZ-diabetes caused marked reduction in serum LH, FSH, prolactin, testosterone and testicular interstitial fluid testosterone as well as the activities of Leydig cellular steroidogenic enzymes (3beta-and 17beta-hydroxysteroid dehydrogenases). Insulin treatment to diabetic rats maintained these changes at control range except FSH and prolactin in prepubertal rats. The results indicate that (i) diabetes-induced steroidogenic lesions in Leydig cells represent a direct consequence of dysfunctioning of pituitary-testicular axis, (ii) the adverse effects of diabetes on pituitary-testicular functions are influenced by age of its induction and (iii) optimum insulin level is essential for the acquisition of Leydig cellular steroidogenic efficacy during sexual development.
The effects of excess corticosterone on luteinizing hormone (LH)-stimulated Leydig cell testosterone production and activity of 11beta-HSD was studied. Adult male rats (200-250 g body weight) were treated with corticosterone-21-acetate (2 mg/100 g body weight, i.m., twice daily) for 15 days. Another set of rats was treated with corticosterone (dose as above) plus LH (ovine LH 100 microg/kg body weight, s.c., daily) for 15 days. Corticosterone administration significantly increased serum and testicular interstitial fluid (TIF) corticosterone but decreased testosterone levels. Administration of LH with corticosterone partially prevented the decrease in serum and TIF testosterone. The oxidative activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) was significantly decreased in Leydig cells of rats treated with corticosterone alone and in combination with LH. The direct effect of corticosterone on Leydig cell steroidogenic potency was also studied in vitro. Addition of corticosterone to Leydig cell culture showed a dose dependent effect on LH-stimulated testosterone production. Corticosterone at 50 and 100 ng/ml did not alter LH-stimulated testosterone production, but at high doses (200-400 ng/ml), decreased basal and LH-stimulated testosterone production. Basal and LH-stimulated cAMP production was not altered by corticosterone in vitro. It is concluded from the present study that elevated levels of corticosterone decreased the oxidative activity of 11beta-HSD and thus resulting in impaired Leydig cell steroidogenesis and the inhibitory effects of corticosterone on testosterone production appear to be mediated through inhibition of LH signal transduction at post-cAMP level.
During the last decade the use of herbal medicinal substances in the attenuation of anterograde and retrograde amnesia induced by electroconvulsive shock (ECS) has been studied using animal research. We will discuss the background of herbal medicine in India, review the research findings on herbal medicines for ECS-induced amnestic deficits, and examine the applications and limitations of animal models in this context. We will focus on our own research and insights, with particular emphasis on practical issues.
Six factorially designed studies evaluated the effects of different schedules of electroconvulsive shocks (ECSs) on alpha-2 adrenoceptor function in the rat brain. Attenuation of the hypomotility response to a clonidine challenge was taken to indicate alpha-2 adrenoceptor downregulation, a putative mediator of antidepressant action. Six daily and six alternate-day ECSs were shown separately to produce this receptor change. Three alternate-day ECSs produced comparable downregulation for a comparable period as six daily ECSs; this suggests that ECS produces time-dependent effects. No changes were elicited with a single ECS, which indicates that a single ECS may not influence alpha-2 receptor function. Three daily ECSs produced brief downregulation, which has implications for receptor dynamics as a function of the ECS schedule. Finally, maintenance ECSs sustained alpha-2 adrenoceptor downregulation over 6 weeks, which suggests a possible neurochemical basis for maintenance electroconvulsive therapy. The clinical relevance and scope for further research are discussed.
Explore the source record for details and available documents.
Prolactin (PRL) binding to Leydig cells in prepubertal and pubertal streptozotocin (STZ)-diabetic and insulin-treated rats was studied. Prepubertal (30-day-old) and pubertal (50-day-old) rats were made diabetic by single injection of STZ (120 and 100 mg/kg b.wt, respectively). After 3 days of STZ administration, a group of rats was given insulin injections subcutaneously (3 U/100 g b.wt/day in 2 equally divided doses). Animals of prepubertal and pubertal groups were killed on postnatal days 51 and 71, respectively. Age-dependent increase in serum testosterone, PRL levels and PRL receptors on Leydig cells were prevented by STZ-diabetes. Insulin administration partly or completely prevented these changes. These results suggest that steroidogenic defects in Leydig cells of prepubertal and pubertal diabetic rats may be associated with decrease in serum PRL levels and its receptors on Leydig cells. Insulin probably has a role in the maintenance of PRL receptor numbers on Leydig cells during pubertal maturation.