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Biomedical subjects

R C Gupta

Publications and source records attributed to R C Gupta.

At least 127 records · Page 7Linked to original sources
PubMed1994

Simultaneous liquid chromatographic determination of centchroman and its 7-demethylated metabolite in serum and milk.

A precise and sensitive high-performance liquid chromatographic assay was developed and validated for determination of centchroman (I) and its 7-demethylated metabolite (II) in human serum and milk. The serum, at alkaline pH, was extracted with diethyl ether. In the case of milk, after precipitation of the milk protein with acetonitrile, the supernatant was evaporated to dryness and then extracted with diethyl ether at alkaline pH. After solvent evaporation the residue was reconstituted in mobile phase. Separations were accomplished by reversed-phase liquid chromatography using a Spheri-5 cyano column. Recoveries of I and II were always > 95%. Excellent linear relationships (r > 0.999) were obtained between the measured and added concentration ratios of the corresponding serum and milk concentrations over a range of 1 to 1000 ng/ml and 2.5 to 1000 ng/ml for I and II, respectively.

Acetonitriles↗
PubMed1994

Quantification of 2,3-dihydro-7-methoxypyrrolo-[2,1-b]-quinazolin-9(1H)-one, a new antiallergic agent, by high-performance liquid chromatography in serum.

The CDRI compound 73/602 (I, 7-methoxydeoxyvasicinone) is an antiallergic agent presently undergoing Phase II clinical trials. A rapid, precise and sensitive high-performance liquid chromatographic assay has been developed and validated for the detection of I in rat serum. The method involves extraction of rat serum samples with diethyl ether after addition of 1 M potassium hydroxide. Separations were accomplished on a RP-18 column using acetonitrile-phosphate buffer (pH 7) (20:80, v/v) as the mobile phase. Recovery of I was always > 90%. An excellent linear relationship (r = 0.9999) was obtained between the quantified and added concentrations over the range of 2.5 to 500 ng/ml. The sensitivity of the assay for 0.5 ml serum was 2.5 ng/ml.

Animals↗
PubMed1994

Determination of ampicillin in serum by high-performance liquid chromatography with precolumn derivatization.

A high-performance liquid chromatographic assay method using precolumn derivatization and fluorescence detection has been developed and validated for the determination of ampicillin in serum. The presented method is simple and provides improved selectivity and sensitivity over other existing HPLC methods. It is linear over the concentration range of 100 to 10,000 ng/ml (method 1) and 2 to 1000 ng/ml (method 2) and the extraction recovery is more than 75%. The coefficient of variation is found to be less than 10% over the concentration ranges studied.

Ampicillin↗
PubMed1994

In vivo acute effects of carbofuran on protein, lipid, and lipoproteins in rat liver and serum.

The objective of this investigation was to determine the changes in proteins, lipids, and lipoproteins in liver and serum of rats acutely intoxicated with carbofuran (1.5 mg/kg sc). Under the influence of carbofuran acute intoxication, analysis of globulin fractions revealed remarkable changes: In liver, the levels of alpha-2, alpha-3, and gamma were significantly elevated while alpha-1 was reduced; in serum, alpha-1 and alpha-3 fractions were elevated while alpha-2, beta, and gamma remained unchanged. A transient increase in total protein and albumin was noted only in liver. Carbofuran produced significant increases in triglycerides and cholesterol in liver that were also seen in serum. In both the liver and serum the levels of low-density-lipoprotein cholesterol (LDL-C) were reduced while the values of very-low-density-lipoprotein cholesterol (VLDL-C) were elevated. The concentration of high-density-lipoprotein cholesterol (HDL-C) was drastically reduced in liver (23% of control) with a proportional rise in serum (176%). In liver, carbofuran caused marked depletion of adenosine triphosphate (ATP) and phosphocreatine (PCr) (38% and 22% of controls, respectively), resulting in increased cell membrane permeability, thereby allowing leakage of cell constituents. It was concluded that carbofuran, directly or indirectly, produced perturbations in lipoprotein metabolism.

Adenosine Triphosphate↗
PubMed1994

Cholinergic and noncholinergic changes in skeletal muscles by carbofuran and methyl parathion.

The objective of this investigation was to determine the distribution of cholinergic (acetyl-cholinesterase, AChE) and noncholinergic markers in slow-, fast-, and mixed-fiber containing muscles (soleus, SOL; extensor digitorum longus, EDL; and diaphragm, DIA, respectively). Noncholinergic markers included high-energy phosphates (adenosine triphosphate, ATP; phosphocreatine, PCr; and their metabolites), and the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) and their isoenzymes and subforms. All three types of muscles had only one CK isoenzyme, CK-MM, which totally consisted of MM3 subform. Levels of these determinants were highest in EDL followed by DIA and least in SOL. Another objective was to determine alterations of these markers under the influence of acute carbofuran (1.5 mg/kg) or methyl parathion (MPTH, 5 mg/kg) toxicity. Rats receiving either insecticide showed cholinergic signs with maximal severity including muscle fasciculations and convulsions within 15-30 min that lasted for about 2 h. At 1 h postinsecticide injection, when AChE was maximally inhibited (81-96%), significant depletion of ATP and PCr was evident in muscles (DIA > SOL > EDL), and activities of CK-MM and LDH were elevated in muscles and consequently in serum. Serum CK-MM3 activity was markedly reduced with sequential increase in MM2 and MM1 subforms, probably due to induced higher carboxypeptidase activity. These findings suggested that (1) the differences in levels of biochemical constituents in muscles depend upon the fiber type, (2) anticholinesterase insecticide-induced increased muscle activity produces characteristic changes in CK and LDH isoenzymes patterns, and (3) leakage of these enzymes/isoenzymes into serum is due to depletion of ATP and PCr, which are required to maintain the cell membrane permeability.

Acetylcholinesterase↗
PubMed1994

Carbofuran toxicity.

Carbofuran, an anticholinesterase carbamate, is commonly used as an insecticide, nematicide, and acaricide in agricultural practice throughout the world. Due to its widespread use in agriculture, contamination of food, water, and air has become imminent, and consequently adverse health effects are inevitable in humans, animals, wildlife, and fish. Currently, carbofuran's involvement is most frequently encountered in malicious poisoning. The literature on chemical properties, acute toxicity data, poisoning incidences, pharmacokinetics, and mechanism of toxicity of carbofuran is briefly reviewed. Much emphasis is given to the metabolism of carbofuran, and the impact of carbofuran and its two major metabolites (3-hydroxycarbofuran and 3-ketocarbofuran) on overall toxicity. Biochemical (cholinergic and noncholinergic), hematological, and immunological effects induced by carbofuran are discussed in detail. Carbofuran and/or its major metabolites can cross the placental barrier and produce serious effects on the maternal-placental-fetal unit. Carbofuran's toxicity can be potentiated by simultaneous exposure with other cholinesterase inhibitors. Literature on various biomarkers of carbofuran exposure and on induced adverse health effects is also presented. To date, a combination of atropine and memantine remains the most effective antidotal treatment against acute carbofuran toxicity.

Agricultural Workers' Diseases↗
PubMed1994

DNA adducts of the ubiquitous environmental contaminant cyclopenta[cd]pyrene.

The bioactivation of cyclopenta[cd]pyrene (CPP) was investigated to determine the major DNA adduct-forming metabolite(s) of this widespread environmental contaminant and suspect carcinogen. DNA adducts were analyzed by 32P-postlabeling. Four major and at least seven minor adducts formed when CPP was incubated with calf thymus DNA in the presence of rat liver microsomal systems. P450 subfamilies IA and IIB both activated CPP as microsomes from either phenobarbital- or beta-naphthoflavone-treated rats produced quantitatively similar and qualitatively identical adducts. When the epoxide hydrolase inhibitors, 1,1,1-trichloropropene-2,3-oxide or cyclohexene oxide were added to the incubations, binding increased 2.5- to 4-fold, suggesting epoxidation as a mechanism of adduct formation in vitro. Sprague-Dawley rats were killed 1, 3, 7, 18, 45 and 80 days postdosing i.p. with 50 mg/kg CPP. In all tissues analyzed, four major and several minor qualitatively identical adducts were produced. Binding was highest and most persistent in lung followed by heart, white blood cells (WBCs) and liver. CPP adducts were detectable at doses from 1 microgram/kg to 50 mg/kg. Rat lung DNA adducts were cochromatographed with standardized deoxyguanosine and deoxyadenosine adducts produced by reaction of CPP-3,4-epoxide in vitro. All rat lung adducts comigrated with the deoxyguanosine adducts but one was clearly deoxyadenosine derived. Mouse skin DNA adducts from NIH Swiss mice and mouse lung DNA adducts from B6C3F1 mice were also analyzed. All adducts from either mouse tissue comigrated with rat lung DNA adducts, suggesting CPP-3,4-epoxide was also the major DNA adduct-forming species in the mouse. CPP-3,4-epoxide has been suggested to be the key mediator of the biological activities of CPP. Evidence presented here strongly suggests CPP-3,4-epoxide as the major adduct-forming species of CPP as catalyzed in vitro by rat liver preparations known to mediate the mutagenic activation of CPP, in the rat in vivo, and in mouse skin and lung, two tissues with known sensitivity to CPP tumorigenicity.

Animals↗
PubMed1994

Creative problem-solving techniques: relevance to doctors in management?

Recent NHS reforms have had a profound impact on the role of clinicians in the field of management. Traditionally this has been a role eschewed by clinicians, but the evolution of the clinical directorate model has now encouraged senior members of the medical profession to address more positively managerial and management issues. If clinicians are to embrace enthusiastically the management role, it is clear that their awareness of the range of techniques available to them is raised to its maximum potential. In this respect, explores the relevance of some more radical creative problem-solving techniques within a practical environment. The concentration is on two specific techniques which were put to trial in real working situations. However, in addition to the techniques addressed, there are a range of alternative problem-solving techniques which may be more appropriate. Having piloted the two creative problem-solving techniques described, the practical conclusions were that their application had developed better team working and spirit, enhanced the quality of patient care delivered by the team and improved productivity and outcomes.

Aged↗
PubMed1994

M2-specific muscarinic cholinergic receptor-mediated inhibition of cardiac regulatory protein phosphorylation.

Acetylcholine acting via muscarinic cholinoceptors decreased phosphorylation of phospholamban and troponin I without reducing adenosine 3',5'-cyclic monophosphate (cAMP) levels or cAMP-dependent protein kinase activity ratio in the presence of 10-100 nM isoproterenol in guinea pig ventricular myocytes. The effect of acetylcholine was more pronounced when adenosine deaminase (5 U/ml) was present and incubation period was short (10 s). Okadaic acid, an inhibitor of protein phosphatase activity, blocked the acetylcholine-mediated inhibition of isoproterenol-stimulated phosphorylation of phospholamban. It is suggested that acetylcholine reduces protein phosphorylation by a cAMP-independent mechanism in guinea pig ventricular myocytes.

Acetylcholine↗
PubMed1994

Effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction.

BACKGROUND: Recent clinical trials have suggested that therapy with angiotensin-converting enzyme inhibitors in asymptomatic patients with reduced left ventricular (LV) function can significantly reduce the incidence of congestive heart failure compared with patients receiving placebo. In the present study, we examined the effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of LV systolic dysfunction and LV chamber enlargement in dogs with reduced LV ejection fraction (EF). METHODS AND RESULTS: LV dysfunction was produced in 28 dogs by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LVEF was 30% to 40%. Three weeks after the last embolization, dogs were randomized to 3 months of oral therapy with enalapril (10 mg twice daily, n = 7), metoprolol (25 mg twice daily, n = 7), digoxin (0.25 mg once daily, n = 7), or no treatment (control, n = 7). As expected, in untreated dogs, LVEF decreased (36 +/- 1% versus 26 +/- 1%, P < .001) and LV end-systolic volume (ESV) and end-diastolic volume (EDV) increased during the 3-month follow-up period (39 +/- 4 versus 57 +/- 6 mL, P < .001, and 61 +/- 6 versus 78 +/- 8 mL, P < .002, respectively). In dogs treated with enalapril or metoprolol, LVEF remained unchanged or increased after therapy compared with before therapy (35 +/- 1% versus 38 +/- 3% and 35 +/- 1% versus 40 +/- 3%, respectively, P < .05), whereas ESV and EDV remained essentially unchanged. In dogs treated with digoxin, EF remained unchanged but ESV and EDV increased significantly. CONCLUSIONS: In dogs with reduced LVEF, long-term therapy with enalapril or metoprolol prevents the progression of LV systolic dysfunction and LV chamber dilation. Therapy with digoxin maintains LV systolic function but does not prevent progressive LV enlargement.

Animals↗
PubMed1994

Pancreatic xenograft survival in diabetic rabbits.

Prolonged survival of pancreatic xenografts in the muscles of diabetic rabbits was achieved. The mean graft survival time (assessed by euglycemic status) in nonimmunosuppressed (Group A) was 10 days and in immunosuppressed (Group B) was 36 days (P < 0.05). Adequate immunosuppression helps pancreatic xenograft to normalize blood glucose level (BGL) by prolonging survival time. Our study demonstrates that xenotransplantation of islet cells in their natural environment (pancreatic tissue in four of thin slices) survive and function adequately in immunosuppressed recipients. This discordant Xenotransplantation model may be useful for future xenotransplantation studies.

Animals↗
PubMed1994

Reversal of clinical and dental fluorosis.

A large number of Indians are forced to consume fluoride contaminated water. Toxic effects of chronic fluoride ingestion are hitherto considered irreversible. In this study 20 children were selected from an area consuming water containing 4.5 ppm of fluoride (Group A) and a second sample of 20 children from another area consuming water containing 8.5 ppm of fluoride (Group B). All the children were in an age group of 3 to 12 years and weighed 12 to 25 kg. Both samples were graded for clinical, radiological and dental fluorosis. All grades of manifestations were observed. These children were given ascorbic acid (500 mg), calcium (250 mg) and vitamin D3 (800 IU) daily. Follow up revealed reversal of clinical and dental fluorosis after 44 days. Improvement in the Group B sample was slower than Group A. Dosage of ascorbic acid was increased to 750 mg per day, keeping the dosages of other drugs unchanged to Group B children. After 15 days of the revised therapy a marked improvement was noticed in clinical and dental fluorosis in this sample also.

Ascorbic Acid↗