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Biomedical subjects

A Verma

Publications and source records attributed to A Verma.

At least 91 records · Page 5Linked to original sources
PubMed1999

Temporal patterns of poly(ADP-ribose) polymerase activation in the cortex following experimental brain injury in the rat.

The activation of poly(ADP-ribose) polymerase, a DNA base excision repair enzyme, is indicative of DNA damage. This enzyme also undergoes site-specific proteolysis during apoptosis. Because both DNA fragmentation and apoptosis are known to occur following experimental brain injury, we investigated the effect of lateral fluid percussion brain injury on poly(ADP-ribose) polymerase activity and cleavage. Male Sprague-Dawley rats (n = 52) were anesthetized, subjected to fluid percussion brain injury of moderate severity (2.5-2.8 atm), and killed at 30 min, 2 h, 6 h, 24 h, 3 days, or 7 days postinjury. Genomic DNA from injured cortex at 24 h, but not at 30 min, was both fragmented and able to stimulate exogenous poly(ADP-ribose) polymerase. Endogenous poly(ADP-ribose) polymerase activity, however, was enhanced in the injured cortex at 30 min but subsequently returned to baseline levels. Slight fragmentation of poly(ADP-ribose) polymerase was detected in the injured cortex in the first 3 days following injury, but significant cleavage was detected at 7 days postinjury. Taken together, these data suggest that poly(ADP-ribose) polymerase-mediated DNA repair is initiated in the acute posttraumatic period but that subsequent poly(ADP-ribose) polymerase activation does not occur, possibly owing to delayed apoptosis-associated proteolysis, which may impair the repair of damaged DNA.

Animals↗
PubMed1999

Succinylcholine induced hyperkalemia and cardiac arrest death related to an EEG study.

Changes in EEGs during cardiac arrest have been described in detail by many authors; however, mortality because of an EEG has never been reported. The authors report the case of a patient who developed cardiac arrest causally related to administration of succinylcholine for reduction of excessive amounts of myogenic artifact during an EEG. This case indicates the need for caution when doing an EEG study in an intensive care unit setting.

Electroencephalography↗
PubMed1999

A case of sustained massive gabapentin overdose without serious side effects.

Gabapentin is an antiepileptic agent that is indicated for use as adjunctive therapy for partial seizures. It has a relatively benign side effect profile, but little data exists on massive overdoses with this agent. The authors present a case of a patient who received a massive overdose of this agent but suffered no clinically significant toxicity.

Acetates↗
PubMed1999

Prescribing habits in primary biliary cirrhosis: a national survey.

BACKGROUND: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown aetiology. A number of drugs have been used in its treatment, but only ursodeoxycholic acid (UDCA) has been shown to improve survival. Our aims were to determine the current prescribing habits in PBC of all practising gastroenterologists in the UK. METHODS: A postal questionnaire was sent to 454 gastroenterologists in 1996, followed by a second questionnaire a month later to the non-responders. RESULTS: Of 454 doctors sent questionnaires, 379 (83%) replied. Of these, 58 were excluded from further analysis as they were not practising gastroenterologists. There are an estimated 4337 patients with PBC being seen by gastroenterologists in hospitals. Of these, only 1376 (32%) are being seen in liver units. Ninety-one per cent of gastroenterologists look after patients with PBC (median 10 patients, range 1-500). Ninety-five per cent of gastroenterologists prescribe UDCA but there is a large dose range (median 11.5 mg/kg/day, range 1.5-23.1). Of these, 93% also prescribe cholestyramine. Only 45 (14%) gastroenterologists prescribed other treatments for PBC (13 colchicine, 24 steroids, nine penicillamine, 13 immunosuppressants). Only 53 (17%) treat the symptoms/complications of PBC (37 fat-soluble vitamins, 15 calcium, six bisphosphonates, one hormone replacement therapy, 10 antihistamines, 10 rifampicin). CONCLUSIONS: UDCA is being prescribed for PBC by the majority of practising gastroenterologists but over a wide dose range. Very few gastroenterologists are using preventive treatment for osteoporosis in this high-risk group. Other treatments, as yet unproven in trials, are being prescribed by a minority of gastroenterologists.

Cholagogues and Choleretics↗
PubMed1999

Optimum dose of ursodeoxycholic acid in primary biliary cirrhosis.

BACKGROUND: Ursodeoxycholic acid (UDCA) improves liver function tests and prolongs survival in primary biliary cirrhosis (PBC). The dose of 10- 15 mg/kg/day used in the large trials has largely been based on that used for gallstone dissolution. The only dose-response study of UDCA in PBC suggested that a dose of 8 mg/kg/day was the most efficacious. However, disease stage of the patients was not known, higher doses of UDCA were not tried and there was no 'washout period' between the different doses. The aim of this study was to determine the optimum dose of UDCA in early-stage PBC (stage 1 and 2). METHODS: Twenty-four biopsy-proven early-stage PBC patients (one male, 23 female) received five doses of UDCA (0, 300, 600, 900, 1200 mg/day) each for 8 weeks with 4-week washout periods between doses. Symptoms (pruritus, fatigue, diarrhoea) were assessed on a four-point scale (none, mild, moderate, severe). Liver function tests (LFTs) were performed using conventional methods, and serum bile acids were measured using gas liquid chromatography. RESULTS: The dose of 900 mg/day produced the greatest enrichment of UDCA in serum bile acids; although there was no difference in the enrichment of UDCA between the different doses. There was a trend towards normalization of the abnormal LFTs in a dose-dependent manner (for y-glutamyl transferase (yGT), alkaline phosphatase (ALP), alanine transaminase (ALT) and IgM). Multi-factorial analysis showed that UDCA treatment, irrespective of dose, was significantly better than placebo for all the variables. The 900 and 1200 mg doses were better than both 300 and 600 mg using yGT and total bilirubin as variables, better than 300 mg using ALP and IgM as variables, and better than 600 mg using albumin as a variable. No variables showed a significant difference between 900 and 1200 mg. CONCLUSION: The optimum dose of UDCA is 900 mg/day (equivalent to 13.5 mg/kg/day).

Adult↗
PubMed1999

Mycobacterium tuberculosis rrn promoters: differential usage and growth rate-dependent control.

Mycobacterium tuberculosis is a slow-growing pathogen and is characterized by a low content of RNA per unit of DNA. rRNAs represent a major proportion of the total RNA pool, and the entire requirement for rRNA is met by transcription from a single rrn operon that is driven by two promoters, P1 and P3. This study attempted to analyze the specific role of the rrn promoter in determining the characteristically low levels of RNA in M. tuberculosis. For this purpose, the activity of the M. tuberculosis rrn promoter as a function of the growth rate was studied by rrn-lacZ promoter fusion, hybridization, and primer extension analysis in M. smegmatis. rrn promoter signals were faithfully recognized in M. smegmatis cultures harboring the rrn-lacZ promoter construct. In M. smegmatis cultures that displayed doubling times varying between 3.06 and 6.5 h, beta-galactosidase activity increased approximately sixfold in proportion to the growth rate (mu). There was a corresponding increase in the amount of lacZ-specific mRNA, while the plasmid copy number remained essentially unchanged. For any given mu, the P3 promoter was approximately twofold more efficiently utilized than the P1 promoter. Since both promoters of the M. tuberculosis rrn operon are regulatable as a function of growth rate in M. smegmatis cultures, it is implied that the inherent structure or sequence of the rrn promoter per se is not primarily responsible for the observed lack of modulation of RNA synthesis in M. tuberculosis.

Base Sequence↗
PubMed1999

Lamotrigine-induced blepharospasm.

Movement disorders such as tremor and ataxia occur commonly during therapy with antiepileptic drugs (AEDs). Dystonias, however, are rare. Blepharospasm, although reported with neuroleptic agents, has never been reported with AEDs. Our patient developed blepharospasm during therapy with lamotrigine.

Anticonvulsants↗
PubMed1999

Human spermatozoal motility and lipid peroxidation.

Correlation between human spermatozoal motility and lipid peroxidation is worked out following their suspension in native seminal plasma and in Biggers, Whitten and Whittengham (BWW) medium. Spermatozoa suspended in BWW showed higher motility and lesser degree of lipid peroxidation than those suspended in seminal plasma. Further, higher activities of antioxidant enzymes are recorded in the BWW suspended spermatozoa vis a vis those suspended in native seminal plasma.

Catalase↗
PubMed1999

Cognitive dysfunction in NIDDM: P3 event related evoked potential study.

P3 component of the endogenous cerebral evoked response is a sophisticated, objective and quantitative approach to assess higher functions of the brain. This test was employed using auditory 'odd ball' paradigm to assess cognitive functions in thirty non insulin dependent diabetic patients (NIDDM) aged 43.6 +/- 9 yrs with poor blood glucose control. (HbAlc. 9.9 +/- 1.0%). The peak latencies of N2, P3 components of event related evoked potentials obtained in these patients were compared with 30 age and sex matched non diabetic healthy controls. Latencies of these potentials were: N2 = 248.0 +/- 36.3, P3 = 391.6 +/- 49.9 msec in NIDDM as compared to 220.6 +/- 26.4, 326.2 +/- 26.8 msec in controls and were highly significant (P < 0.001). The duration of disease, blood glucose level or the physical parameters of height, weight and blood pressure did not show any correlation with N2 or P3 latencies or amplitude. These findings provide an electrophysiological evidence of delayed cognition in poorly controlled NIDDM cases.

Adult↗
PubMed1999

Effect of vitamin E on human sperm motility and lipid peroxidation in vitro.

AIM: To assess the protective efficacy of vitamin E to counteract the reactive oxygen species (ROS) mediated damage on sperm motility, viability and lipid peroxidation. METHODS: Human semen samples were obtained from the local hospital. The split seminal fractions freed of seminal plasma were reconstituted in Ringer-Tyrode and subjected to varied vitamin E concentrations (0.1-2 mmol/L). RESULTS: Dose-dependent improvement in both motility and viability accompanied by concomitant decrease in malondialdehyde (MDA--an end product of lipid peroxidation) following vitamin E supplementation was noticed. CONCLUSION: Vitamin E protects against the ROS mediated damage on spermatozoa. Vitamin E supplementation could be of clinical importance for prolonged spermatozoal storage whenever needed.

Humans↗
PubMed1998

Regulation of striatal dopamine release by metabotropic glutamate receptors.

In vivo microdialysis in conscious rats was used to assess the effect of metabotropic glutamate receptor stimulation on striatal dopamine release. Local application of the metabotropic glutamate agonist (+/-)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), via a microdialysis probe, produced a concentration-dependent response: infusion of 50 microM ACPD did not produce a significant effect on extracellular dopamine levels, while application of 100 microM or 500 microM ACPD increased dopamine release by approximately 50% or 100%, respectively. To examine the contribution of impulse flow and multisynaptic mechanisms to the ACPD-induced increase in dopamine release, 500 microM ACPD were coapplied with 2 microM tetrodotoxin (TTX). An increase in extracellular dopamine levels was observed after the application of 500 microM ACPD, despite the presence of TTX. To further study the actions of metabotropic glutamate receptor-stimulation on terminal release characteristics of dopamine, the effect of ACPD on 40 mM K+-stimulated dopamine release was investigated. It was found that application ofACPD reduces dopamine release in response to K+ stimulation. These data suggest that during basal conditions, metabotropic glutamate receptor activation facilitates striatal dopamine release, possibly through presynaptic, impulse-independent mechanisms. However, during conditions of hyperstimulation, activation of metabotropic receptors, in contrast to ionotropic receptors, reduces excess dopamine release.

Animals↗
PubMed1998

Metabolism and toxicity of aflatoxins M1 and B1 in human-derived in vitro systems.

Aflatoxin M1 (AFM1) is the principal hydroxylated aflatoxin metabolite present in the milk of dairy cows fed a diet contaminated with aflatoxin B1, (AFB1) and the metabolite is also present in the milk of human nursing mothers consuming foodstuffs containing the toxin. AFM1 is usually considered to be a detoxification product of AFB1 and this appears warranted if the biological endpoints involved are carcinogenicity and mutagenicity. However, it may not be a valid conclusion in the case of cytotoxicity. The metabolism of AFM1 and AFB1 have been studied in vitro using human liver microsomes. Formation of primary metabolites associated with metabolic activation to the respective epoxides reflected the differences between the carcinogenic potentials of the two toxins and, similar to AFB1, the conjugation of AFM1 epoxide with reduced GSH was catalyzed by mouse, but not human liver cytosol. Although the majority of the binding of [3H]AFB1 to microsomal protein was dependent on metabolic activation, a high level of retention of [3H]AFM1 by microsomes, nonextractable in methanol and unrelated to metabolic activation, was observed. It appears possible that this property is related to the high cytotoxicity of AFM1. Experiments using human cell line cells either expressing or not expressing human cytochrome P450 enzymes in assays of acute toxicity (MTT assays) have demonstrated a directly toxic potential of AFM1 in the absence of metabolic activation, in contrast to AFB1. Caution therefore needs to be exercised in designating the formation of AFM1 as essentially detoxification when considering a biological response in which cytotoxicity may play a significant role, e.g., immunotoxicity.

Aflatoxin B1↗
PubMed1998

Human sperm motility and lipid peroxidation in different ascorbic acid concentrations: an in vitro analysis.

Human spermatozoal motility, viability and lipid peroxidation (LPO) have been assessed in Ringer-Tyrode supplemented with different concentrations of ascorbic acid (AA) ranging from 50 to 4000 microM. Ascorbic acid in concentrations below 1000 microM protects spermatozoa from free radical damage as evidenced from improvement in their motility and viability. Concomitantly, there is also witnessed depletion of malondialdehyde generation (an end product of LPO) following AA treatment. Ascorbic acid at 1000 microM concentration and above, however, is not protective, as evidenced by abrupt fall in sperm motility and viability and concomitant increase in LPO.

Antioxidants↗
PubMed1998

Diagnostic yield in computed tomography guided stereotactic biopsies.

Fifty three patients underwent computerised tomography (CT) guided stereotactic biopsies from different CT defined zones of attenuation with the Leksell stereotactic apparatus from October 1993 through January 1995. Multiple lesions were seen in 16 cases and 3 of them had multiple rim enhancing lesions. Astrocytoma was the most common histological diagnosis and thalamus was the commonest site of these tumours. The overall positivity rate was 98.2%. Positive yield from the centre of the lesion, peripheral and perilesional areas was 92.1%, 54.7% and 17.6%, respectively. The definite pathological diagnosis was made in 81.1% of cases. Post-operative neurological worsening was seen in 6 patients, of which 2 recovered without any surgical treatment, in 1 patient ventriculo-peritoneal shunt was done post-biopsy whereas in another evacuation of hamatoma was done which relieved headache and vomiting while 2 patients (3.7%) died.

Adolescent↗
PubMed1998

Photodynamic tumor therapy: mitochondrial benzodiazepine receptors as a therapeutic target.

BACKGROUND: Photodynamic therapy employs photosensitive agents such as porphyrins to treat a variety of tumors accessible to light-emitting probes. This approach capitalizes on the selective retention of porphyrins by cancer cells. Cancer cells also have elevated levels of mitochondrial benzodiazepine receptors which bind porphyrins with high affinity. METHODS: Cultured cancer cell lines were exposed to porphyrin and porphyrin-like compounds and then irradiated with light. Cytotoxicity of this treatment was measured via clonogenic assays. Mitochondrial benzodiazepine receptor pharmacology was studied using [3H] PK11195 binding to cancer cell homogenates and isolated kidney mitochondrial membranes. RESULTS: We show that therapeutic potencies of porphyrins correlate closely with affinities for mitochondrial benzodiazepine receptors. Sensitivities of tumor cell lines to photodynamic therapy parallel their densities of these receptors. CONCLUSION: We propose that porphyrin photodynamic therapy is mediated by mitochondrial benzodiazepine receptors.

Mitochondria↗
PubMed1998

Cytogenetic investigations on patients with oral submucous fibrosis.

Lymphocyte cultures were set up from venous blood samples collected from 23 patients of submucous fibrosis (SMF) and 10 normal controls. Slides, thus prepared, were processed and screened for G-, C-banding and sister chromatid exchange (SCE) frequency analysis. No gross chromosomal anomalies except that a few breaks and gaps were observed to be randomly distributed throughout the genome. However, a proportionate increase in SCE frequency in SMF patients as compared to the normal control individuals was observed. An attempt has been made to correlate the period of betel leaves, nuts, quid and tobacco chewing with the incidence of chromosomal anomalies and increase in SCE frequency and its sexwise distribution in these patients.

Areca↗