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Biomedical subjects

R C Gupta

Publications and source records attributed to R C Gupta.

At least 19 recordsLinked to original sources
PubMed1995

Sensitive high-performance liquid chromatographic assay method for the determination of guggulsterone in serum.

Guggulsterone (I) is a new hypolipidemic agent, being developed at CDRI (Lucknow, India). A sensitive high-performance liquid chromatographic assay in serum has been developed and validated for the determination of guggulsterone in serum for pharmacokinetic studies. This assay method consists of extraction of the drug with hexane from spiked human serum samples. Separation was achieved using C18 reversed-phase column coupled with photodiode array detector, and an acetonitrile-water mixture as mobile phase. The method described herein is simple and has limit of quantitation of 10 ng/ml as compared to 200 ng/ml by the previous reported method. The standard curve was linear over the range of 10-1000 ng/ml in mobile phase as well as in normal human serum. Analytical recovery of I added to serum was > 90%. The reproducibility was determined by the inter- and intra-assay variations which were < 10%.

Administration, Oral↗
PubMed1995

Sensitive high-performance liquid chromatographic method for the determination of methyl N-[5-[[4-(2-pyridinyl)-1-piperazinyl]carbonyl]-1H-benzimidazol-2-yl d carbamate in rat blood.

A sensitive high-performance liquid chromatographic assay has been developed and validated for the determination of methyl N-[5-[[4-(2-pyridinyl)-1-piperazinyl]carbonyl]-1H-benzimidazol-2-y l d carbamate (CDRI compound 81/470) in normal rat blood. The method described herein is simple, with improved selectivity and sensitivity over a previously reported HPLC method. The limit of quantitation is 10 ng/ml (method 1) and 2.5 ng/ml (method 2) in blood, as compared with 40 ng/ml for the previous method. The standard curve in blood is linear over the concentration range 10-1000 ng/ml in method 1 and 2.5-1000 ng/ml in method 2 and the extraction recovery is higher than 80% for both methods.

Animals↗
PubMed1995

32P-postlabeling analysis of DNA adducts formed in vitro and in rat skin by methylenediphenyl-4,4'-diisocyanate (MDI).

The 32P-postlabeling method was adapted for the detection of DNA adducts formed by methylenediphenyl-4,4'-diisocyanate (MDI). Incubation of the 3'-phosphates of the deoxyribosides of cytosine (C), adenine (A), guanine (G) and thymine (T) with MDI in Tris buffer resulted in the formation of 5, 7, 8, and 2 reaction products, respectively. Incubation of DNA with MDI resulted in detectable levels of 5, 2, and 1 adducts attributable to C, A, and G. Analysis of DNA isolated from the epidermis of rats treated dermally with 9 mg MDI showed an adduct pattern similar to the one seen in the in vitro DNA incubation. A total adduct level of 7 per 10(8) nucleotides was measured, the limit of detection was 2 adducts per 10(10) nucleotides. The data indicate that a minute fraction of MDI can reach DNA in vivo in a chemically reactive form. In comparison with the genotoxic skin carcinogen 7,12-dimethylbenz[a]anthracene on the other hand, the DNA-binding potency of MDI was more than 1000-fold lower.

Animals↗
PubMed1995

Increased incidence of spina bifida occulta in fluorosis prone areas.

Spina bifida, a congenital deformity of the posterior wall of vertebrae of the spine, is a midline defect of skin, vertebral arches and neural tube, usually in the lumbosacral region. Its incidence is reported to be 0.2 to 0.4 per 1000 live births. Various hypotheses have been put forward as etiological factors for spina bifida including consumption of potato affected by blight and hardness of drinking water but these have not been proven. Two groups of 50 randomly chosen children were established. The study group consisted of children aged 5 to 12 years, weighing 15 to 30 kg, consuming fluoride rich drinking water (4.5 and 8.5 ppm fluoride; WHO permissible limit is 1.5 ppm fluoride), and manifesting either clinical, dental and/or skeletal fluorosis. The control group consisted of age and weight-matched children, consuming less than or equal to 1.5 ppm fluoride in drinking water and not showing any evidence of fluoride toxicity. These children were evaluated for antenatal history, general clinical examination (especially for dimples, tufts of hair, haemangioma on skin throughout the length of spine), other congenital abnormalities, evidence of fluoride toxicity, biochemical estimation for fluoride levels in blood and serum and by skiagrams of the spine to examine for the presence of spina bifida occulta. A total of 22 (44%) of the 50 children in group A, the study group, and 6 (12%) of the 50 children in group B, the control group, revealed spina bifida occulta in the lumbosacral region.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies↗
PubMed1992

DNA adducts in carp exposed to artificial diesel-2 oil slicks.

In attempts to mimic field exposure, oil slicks prepared from diesel-2 oil/water emulsions were poured onto the surface of water in tanks prepared fresh every day and liver DNA adducts were analyzed by 32P-postlabeling in carp free-swimming in these tanks. 'Clusters' of lipophilic DNA adducts were detected, with five major and numerous minor adducts. Essentially a similar adduct pattern was found in the liver DNA of carp exposed to crude oil-polluted water. Diesel-2 adduct induction was observed slowly with a steady increase to greater than 3000 amol/microgram DNA at day 12. After this time fish were transferred to clean water. Adduct levels continued to increase through day 17 (approximately 10,000 amol/microgram DNA) despite the cessation of exposure, but a 30% and 80% decline was evident at day 22 and day 27, respectively. All major adducts were distinct from the known benzo[a]pyrene diolepoxide-dG. These results indicate that diesel-2 oil can cause extensive DNA damage in carp in vivo and the damage accumulates proportionately with time of exposure.

Animals↗
PubMed1992

Carcinogen-DNA adducts in cultures of rat and human hepatocytes.

Exposure to chemical carcinogens can often be identified by detection of DNA adduct lesions. Primary cultures of isolated rat and human hepatocytes were exposed to 2-acetyl-aminofluorene (AAF), 4-aminobiphenyl (ABP), or benzo[a]pyrene (BP). The isolated DNA from the exposed cells was analyzed using the 32P-post-labeling assay. A greater total of carcinogen-DNA adducts, 2-12-fold, were observed in human hepatocytes than rat hepatocytes at the same concentrations. The predominant DNA adducts for each carcinogen were the same between rat and human cells. The N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF) was the major AAF-DNA adduct. The N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP) was the major ABP-DNA adduct. In the rat N2-[10 beta-(7 beta, 8 alpha, 9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene)yl] deoxyguanosine (dG-N2-BP) and two unidentified adducts were nearly equivalent in amount, while the major BP-DNA adducts in the humans was the dG-N2-BP. The rat hepatocyte in vitro results are comparable to the predominant adducts found with rats exposed in vivo. The two different cultures of human hepatocytes demonstrated qualitative and quantitative differences in specific DNA adducts from rat hepatocytes. This study and others using human hepatocyte cultures demonstrate that this in vitro system can provide useful information for assessing human carcinogenic hazards.

2-Acetylaminofluorene↗
PubMed1992

Prophylactic and therapeutic efficacy of memantine against seizures produced by soman in the rat.

Male Sprague-Dawley rats injected sc with a single sublethal dose of the organophosphate nerve agent, soman (100 micrograms/kg), had motor limbic seizures within 5-15 min. Pretreatment with a single dose of memantine HCl (MEM, 18 mg/kg, sc), alone or in combination with atropine sulfate (ATS, 16 mg/kg, sc), before soman prevented seizures without sedation or ataxia. Rats appeared normal or demonstrated increased exploratory activity. Excessive salivation, a peripheral manifestation of soman intoxication, was decreased by ATS, but pretreatment with ATS alone did not prevent seizures. After seizure onset, MEM +/- ATS, but not ATS, abolished seizures. Acetylcholinesterase (AChE) activity in several brain regions (cortex, stem, striatum, and hippocampus) was markedly reduced by soman, but not by MEM, ATS, or MEM + ATS. Preadministration of MEM + ATS in vivo significantly protected AChE from inhibition by soman. Memantine reduced inhibition of AChE activity in crude brain homogenates by soman, but not by edrophonium (anionic site inhibitor) or decamethonium (peripheral site inhibitor). Thus, MEM may bind to a different modulatory site, not yet characterized, to protect AChE. When given after onset of soman-induced seizures, treatment with MEM +/- ATS did not reactivate AChE although seizures were controlled, suggesting additional anticonvulsant mechanisms of action. At concentrations (10(-4) to 5 x 10(-4) M) which did not significantly alter the spontaneous firing of action potentials (APs), MEM limited sustained high frequency repetitive firing (SRF) induced by depolarization of spinal cord (mouse and rat) and neocortical (mouse) neurons in monolayer-dissociated cell culture. In the same range of concentrations, ATS both limited SRF and suppressed spontaneous activity, suggesting toxicity. In addition, MEM and ATS reversibly produced use-dependent block of depolarizing responses to acetylcholine (ACh) applied by pressure ejection to spinal cord neurons. Thus, the anticonvulsant efficacy of MEM, with or without ATS, may have resulted from a combination of actions, including protection of AChE from inhibition by soman, limitation of high frequency firing of APs, and blockade of excitatory postsynaptic responses to ACh.

Animals↗
PubMed1992

DNA adducts and induction of sister chromatid exchanges in the rat following benzo[b]fluoranthene administration.

Benzo[b]fluoranthene (B[b]F) was administered (100 mg/kg by i.p. injection) to male Sprague--Dawley rats. Lungs, livers and peripheral blood lymphocytes (PBLs) were harvested 1, 3, 5, 7, 14, 28 and 56 days after treatment. Several DNA adducts were observed in each tissue, with maximal levels occurring at approximately 7 days after treatment. Lung DNA exhibited consistently higher adduct levels than liver or PBL DNA. At 56 days after B[b]F administration, the adducts in liver and PBL DNA were present at < 10 amol/microgram DNA, while in lung there were 100 amoles/microgram DNA. No significant differences were observed between tissues in the types of adducts produced. Co-chromatography with synthetic standards showed that only a minor adduct produced in vivo is derived from trans-9,10-dihydro-9,10-dihydroxybenzo[b]fluoranthene-11,12-oxide. Sister chromatid exchanges (SCEs) from whole blood cultures were significantly increased relative to concurrent controls between 1 and 14 days after B[b]F administration, with maximum levels at 14 days. By 28 days after treatment, SCEs had essentially returned to control levels. SCE induction did not correlate with the amount of B[b]F--DNA adducts remaining in the PBLs at harvest time.

Animals↗
PubMed1992

A comparative study of bronchodilator actions of ipratropium bromide (atrovent) & salbutamol (ventolin) on exercise induced bronchial asthma.

The bronchodilator actions of salbutamol and ipratropium bromide were compared in 30 established cases of bronchial asthma, before and after exercise. It was noticed that after exercise (brisk walk for 3 min.) the PFT values of FVC, PEFR and FEV-1, decreased remarkably from the basal values, the mean fall of 17.91%, 10.68% & 14.8% respectively was noticed. Salbutamol showed improvement in FVC, PEFR, FEV-1, of 20.86%, 15.96% & 17.98% respectively from basal values, while Ipratropium bromide showed improvement by 18.31%, 13.01% & 20.90% respectively. It was also noted that salbutamol is a better drug amongst smokers, patients with family history of bronchial asthma, and in younger age groups. Ipratropium bromide was better in elderly patients (> 40 yrs.) and in those with eosinophillia.

Adult↗
PubMed1992

Effect of dietary salt (NaCl) supplementation on urinary profile of guinea pigs (Cavia porcellus).

Sodium chloride supplementation (120 mg/kg of body weight/day) for 12 days increased the urinary excretion of calcium from 91.6 +/- 9.0 to 159.4 +/- 16.0 mumol/day and of sulphate from 266.8 +/- 24.5 to 1176.9 +/- 87.2 mumol/day in guinea pigs. The stone risk due to increased urinary calcium excretion could possibly be counterbalanced by increasing urinary sulphate excretion. High salt intake, thus, could not increase the risk of stone formation.

Animals↗
PubMed1992

Effect of five-membered heterocycles against Leishmania donovani infection.

Impact of change of heteroatom in pentavalent heterocycles, viz., pyrroles, isoxazoles, imidazoles and crotonates on the profile of antileishmanial activity against amastigotes of L. donovani using in vivo test system and macrophage-amastigote culture system has been studied. Sixty-three compounds were tested. Nine imidazoles showed marginal activity in vivo, whereas 3 out of 10 compounds of isoxazolone series and 2 out of 4 substituted aminocrotonates exhibited antileishmanial activity. Of the 30 substituted pyrroles, except 8 all showed antileishmanial activity in vivo on day 7 post treatment.

Animals↗
PubMed1992

Potential of memantine, D-tubocurarine, and atropine in preventing acute toxic myopathy induced by organophosphate nerve agents: soman, sarin, tabun and VX.

Male Sprague-Dawley rats when administered sc a sublethal dose of organophosphorus cholinesterase inhibitors such as the nerve agents, soman (100 micrograms/kg, sc), sarin (110 micrograms/kg, sc), tabun (200 micrograms/kg, sc), or VX (12 micrograms/kg, sc), developed seizures and severe muscle fasciculations within 15-20 min, lasting for 4-6 hr. Marked inhibition of acetylcholinesterase (AChE) and necrotic lesions in skeletal muscles such as soleus, extensor digitorum longus, and diaphragm were evident between 1-24 hr following injection. Pretreatment with memantine HCl (MEM, 18 mg/kg, sc) together with atropine sulfate (ATS, 16 mg/kg, sc), 60 min and 15 min, respectively, prior to nerve agents attenuated AChE inhibition, prevented myonecrosis, and muscle fasciculations as well as other signs of cholinergic toxicity. Pretreatment combining d-tubocurarine (d-TC, 0.075 mg/kg, sc) and ATS (16 mg/kg, sc) prevented the myonecrosis and fasciculation without protecting AChE against inhibition by these nerve agents. Neither MEM, d-TC, nor ATS in the concentration given interfered with the normal behavior of the rats. The role of d-TC and ATS interaction with presynaptic receptors regulating ACh release and MEM's role in modulating neural hyperactivity as protective mechanisms are discussed.

Acetylcholinesterase↗
PubMed1992

Acute lymphoblastic leukaemia presenting as breast mass.

A 14 year old girl presented with bilateral symmetrical involvement of the breast with acute lymphoblastic leukaemia (ALL). Treatment with combined therapy of adriamycin, vincristine and prednisolone produced a remission in the leukaemia with complete resolution of the breast mass.

Adolescent↗