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Biomedical subjects

S K Gupta

Publications and source records attributed to S K Gupta.

At least 451 records · Page 25Linked to original sources
PubMed1993

Reversible impairment of glucose tolerance in patients with endemic fluorosis. Fluoride Collaborative Study Group.

Endemic fluorosis is a condition resulting from prolonged ingestion of drinking water which contains excess fluoride. Studies on rats have suggested that fluoride toxicity may produce glucose intolerance and abnormalities in insulin secretion. We studied glucose and insulin profiles following an oral glucose load in patients with endemic fluorosis. Twenty-five young adults (age range, 15-30 years) with endemic fluorosis, and an equal number of matched healthy control subjects with normal fluoride intake were studied. Impaired glucose tolerance was demonstrated in 10 of 25 (40%) patients with endemic fluorosis. Patients with impaired glucose tolerance had significantly higher fasting serum immunoreactive insulin (p < 0.05), higher fasting serum fluoride (p < 0.001), and a significantly lower fasting glucose to insulin ratio than that in patients with normal glucose tolerance (p < 0.001) or control subjects (p < 0.05). The fasting serum fluoride levels correlated positively with the area under the glucose curve (r = 0.80, p < 0.01) in patients with impaired glucose tolerance. Interestingly these abnormalities could be reversed when the village was provided drinking water with fluoride levels within acceptable limits. The present study shows that chronic fluoride toxicity in humans could result in significant abnormalities in glucose tolerance which are reversible upon removal of the excess fluoride.

Adolescent↗
PubMed1993

Desensitization of D1 dopamine receptors down-regulates the Gs alpha subunit of G protein in SK-N-MC neuroblastoma cells.

The effect of long-term (72 h) treatment with dopamine D1 receptor agonists, SKF 38393 and dopamine on D1 dopamine receptor and G-protein (Gs alpha) was investigated in SK-N-MC neuroblastoma cells. The prolonged treatment of cells with 10 microM SKF 38393 or 10 microM dopamine resulted in a decrease in dopamine D1 receptor by 41 and 81%, respectively, as measured by specific antagonist [3H]SCH 23390 binding. Similarly, the prolonged treatment of SK-N-MC cells with 10 microM SKF 38393 or 10 microM dopamine resulted in a reduction of the level of Gs alpha subunit of G-protein. The results indicate that agonist-induced down-regulation of D1 dopamine receptor may also modulate G-proteins.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Delineation of epitopes on porcine zona pellucida relevant for binding of sperm to oocyte using monoclonal antibodies.

Seven monoclonal antibodies (MAs) generated against porcine zona pellucida glycoprotein, ZP3 (comprising both ZP3 alpha and ZP3 beta) were characterized for their specificities to ZP3 alpha (MA 7 and MA 28) or ZP3 beta (MA 1, MA 2, MA 10, MA 27 and MA 30) and their relative affinities in competitive ELISA. Among the seven MAs tested, MA 28 showed the highest affinity for ZP3 and ZP3 alpha and MA 30 for ZP3 beta. All the antibodies bound to the zona pellucida in an indirect immunofluorescence assay, but only four (MA 7, MA 28, MA 10 and MA 30) were able to inhibit the binding of boar sperm to the porcine oocyte. Reduction followed by carboxyamidomethylation of the antigen or its chemical deglycosylation reduces reactivity to MA 7 and MA 10, suggesting that these antibodies read conformational or discontinuous determinants. The epitope recognized by MA 28 is sequential or conformational, stabilized by disulfide bonds while MA 30 reads a sequential determinant. ZP3 alpha digested with alpha-chymotrypsin, trypsin and V8 protease, respectively, revealed fragments in the range of 27-20 kDa with MA 28 in immunoblots. Proteolytic digests of ZP3 beta show that MA 30 recognizes approximately 14 kDa fragment of an alpha-chymotrypsin digest and a approximately 6 kDa fragment of a tryptic digest. These studies will help in delineation of smaller determinants of ZP involved in sperm binding.

Animals↗
PubMed1993

Antibody response against epitopes on hCG mapped by monoclonal antibodies in women immunized with an anti-hCG vaccine and its implications for bioneutralization.

The immunological determinants on hCG, to which an antibody response is generated in women by the contraceptive HSD vaccine, were mapped by using a panel of anti-hCG monoclonal antibodies. Two types of inhibition enzyme immunoassays (EIAs) were used to analyze 126 serum samples from 18 subjects immunized with the vaccine and protected from pregnancy. Monoclonal antibody (MAb) 357-2, which recognizes beta-hCG loop peptide 38-57, did not inhibit significantly the binding of immune sera to hCG. Moreover, none of the sera reacted with this loop peptide in a direct binding EIA, suggesting weak immunogenicity of this epitope. All sera competed with MAb 206 and a preponderance of antibodies was seen against this epitopic region on beta-hCG. The antibody titers against the MAb 206 epitope showed a good correlation with the bioneutralization capacity of the sera throughout the course of immunization. These studies indicate the presence of an immunodominant antigenic determinant on hCG as recognized by the human immune system.

Animals↗
PubMed1993

Block in porcine gamete interaction by polyclonal antibodies to a pig ZP3 beta fragment having partial sequence homology to human ZP3.

A murine monoclonal antibody (MA-30) recognizing a sequential epitope on porcine zona pellucida-3 beta glycoprotein (ZP3 beta) and capable of inhibiting sperm-egg interaction was previously described. Polyclonal antibodies against a approximately 6 kDa fragment from the tryptic digest of ZP3 beta, reacting with MA-30, can also inhibit porcine gamete interaction in vitro. Partial N-terminal sequencing of the smallest fragment from the ZP3 beta tryptic digest having reactivity with MA-30 shows sequence homology with human ZP3.

Amino Acid Sequence↗
PubMed1993

A study of effects of putative neurotransmitters injected into the lateral cerebral ventricle of man.

1. The study was carried out in adult patients having normal cardiovascular reflexes and no brain stem lesions. They were exposed to ambient temperature of 72-74 degrees F. Injections of agonists and antagonists of receptors were made into the lateral cerebral ventricles of these patients through diagnostic burr hole in the skull. 2. Noradrenaline, adrenaline and dopamine evoked hypotension and bradycardia. While the core temperature was reduced by nor-adrenaline and adrenaline, dopamine evoked hyperthermia. Isoprenaline elicited hypertension, tachycardia and hyperthermia. Opposite cardiovascular and thermal effects were observed with blockade of alpha 1-, beta-and dopamine receptors with prazosin, propranolol and haloperidol respectively. 3. Injection of 5-hydroxytryptamine resulted in hypertension, tachycardia and hyperthermia but hypotension, bradycardia and hypothermia were seen with methysergide. 4. Similarly, carbachol injection caused initial excitatory followed by inhibitory cardiovascular responses. These were associated with hypothermia. On the contrary atropine per se elicited hypertension, tachycardia and hyperthermia. 5. Thus, alpha 1- and beta-adrenoceptors, dopaminergic, serotonergic and muscarinic cholinergic receptors are present in human brain which appear to modulate cardiovascular activity and core temperature.

Adult↗
PubMed1993

Detection of antigens of Mycobacterium tuberculosis in patients of infertility by monoclonal antibody based sandwiched enzyme linked immunosorbent assay (ELISA).

A sandwich ELISA to detect specific protein antigens of Mycobacterium tuberculosis was developed by using polyclonal anti-BCG rabbit antibodies as the primary capture antibodies. The mycobacterial antigens were detected with horseradish peroxidase conjugated monoclonal antibodies (P 6) as secondary antibodies. The enzyme was detected by using 1,2 Phenylenediamine dihydrochloride (OPD) and Hydrogen peroxide as substrate. The antigen could be quantitated through linear regression analysis with lower detection limit of 1.25 micrograms/ml. 50 consecutive cases of infertility were examined by laparoscopy and tested for the presence of the antigen in the serum. Mycobacterial antigen could be detected in 9 of the 12 cases with definitive diagnosis of tuberculosis, 5 of the 23 where the diagnosis of tuberculosis was probable and in only 1 of 15 patients who had no laparoscopic abnormalities indicative of tuberculosis.

Adult↗
PubMed1993

Interpretation and utilization of effect and concentration data collected in an in vivo pharmacokinetic and in vitro pharmacodynamic study.

The effect (E) of some drugs may be monitored in vitro using the plasma drug concentration (C) following the in vivo dosing of drug. When using a specific analytical assay, counterclockwise hysteresis in the E vs C relationship can be explained only by the presence of an agonistic metabolite (MA); the extent of hysteresis will depend upon the pharmacokinetics and relative "potency" of C and MA. If a nonspecific assay is used, plots of E vs C may actually relate to E vs total agonist (C + MA), and unusual hysteresis may be observed, e.g., clockwise hysteresis when C is more "potent" than MA. Here, we simulate data for three models of relative C and MA pharmacokinetics. The E vs C and E vs MA data are simulated for both linear and noncompetitive agonist Emax models. When C and MA are equally potent, hysteresis will not be observed in a plot of E vs C + MA. However, when C and MA are of differing "potencies," hysteresis will be observed (the direction of hysteresis is dependent on the relative potency of C and MA). By appropriately "weighting" a respective agonist (C or MA), hysteresis will "collapse" and the relative potencies of C and MA can be estimated.

Models, Theoretical↗
PubMed1993

Transdermal fentanyl for cancer pain. Repeated dose pharmacokinetics.

BACKGROUND: The transdermal therapeutic system (fentanyl), or TTS(fentanyl), continuously delivers fentanyl for up to 72 h. The transdermal therapeutic system (fentanyl)-100 delivers approximately 100 micrograms/h. The repeated dose pharmacokinetics of this drug using the recommended dosing interval have not been evaluated previously and were determined in the present study. METHODS: Blood samples were obtained from ten opioid-tolerant cancer patients who received five applications of TTS(fentanyl) at 72-h intervals. A sample of venous blood was taken before each dose; multiple samples were taken during and after the fifth application. A gas chromatographic/mass spectrometry method was used to assay fentanyl (limit of detection 0.2 ng/ml). RESULTS: For the fifth dose, the mean (SD) maximum concentration was 2.6 (1.3) ng/ml and the mean (SD) area under the serum fentanyl concentration-time curve (0-72 h) was 116.9 (59.9). Following removal of the system, the mean (SD) apparent half-life was 21.9 (8.9) h. There were no differences among the serum fentanyl concentrations measured before the second through fifth doses. Fentanyl absorption was 47% complete at 24 h, 88% complete at 48 h, and 94% complete at 72 h. The mean (SD) dose delivered during the 72-h period was 4.3 (1.1) mg. A first-dose trough concentration predicted from fifth-dose kinetics and the actual first-dose trough concentration were very similar. Adverse effects ascribed to the transdermal system were minimal. CONCLUSIONS: These results suggest that steady-state serum concentrations are approached by the second dose of TTS(fentanyl) and that the kinetics are stable with repeated dosing. The apparent half-life following system removal is relatively long, indicating ongoing absorption from a subcutaneous depot.

Administration, Cutaneous↗
PubMed1993

Simultaneous modeling of the pharmacokinetic and pharmacodynamic properties of enalkiren (Abbott-64662, a renin inhibitor). II: A dose-ranging study in patients with congestive heart failure.

This study describes the relationship between the measured effects (the acute effects on systemic hemodynamics and cardiac function) and plasma drug levels using a combined pharmacokinetic-pharmacodynamic model after i.v. infusion dosing of enalkiren (A-64662) in patients with congestive heart failure. Ascending doses from 0.003 to 1.0 mg/kg were evaluated. Timed blood samples were obtained to measure enalkiren levels in plasma. The plasma level-effect plots showed little or no hysteresis. A sigmoid Emax model was used to develop the relationship between the predicted plasma enalkiren levels and hemodynamic effects. Although hemodynamic effects were observed for most patients, random noise in the dynamics or modest net effects compared to baseline fluctuations precluded simultaneous modeling of the pharmacokinetics and pharmacodynamics for a few patients. While the sensitivity toward enalkiren's effects varied substantially among this group of patients, the studywide estimates of the EC50 for the blood pressure measures averaged about 3,500 ng/ml. The mean EC50 for systolic blood pressure (SBP, 2,744 ng/ml) was lower than those of diastolic blood pressure (DBP, 3,438 ng/ml) and mean arterial pressure (MAP, 3,371 ng/ml), suggesting that the SBP might be a more sensitive measure than the other two.

Adult↗
PubMed1993

Skeletal scintigraphic findings in endemic skeletal fluorosis.

Endemic skeletal fluorosis is characterized by bone, joint and muscle pain, progressive ankylosis of various joints and crippling deformities. Whole body skeletal scintigraphy with 99Tcm-methylene diphosphonate was performed for 17 symptomatic subjects suffering from this disorder. The fluoride content of drinking water ranged from 4.1 to 12.9 mg l-1 (normal < 1 mg l-1). Urinary and serum fluoride levels were markedly elevated. Serum calcium (total and ionized), inorganic phosphorus, creatinine and albumin were essentially normal while serum alkaline phosphatase was elevated in six subjects (mean +/- S.D. 206 +/- 106; range 22-1072 IU l-1). Skeletal radiology revealed a wide spectrum of bony abnormalities. Skeletal scintigraphy revealed a picture similar to metabolic 'superscan' in all subjects, i.e. increased tracer uptake in axial and appendicular skeleton, reduced soft tissue uptake, poor or absent renal images, prominent costochondral junction and 'tie' sign in sternum. Increased uptake was present in all subjects irrespective of age, water fluoride content, serum alkaline phosphatase level and radiological abnormalities. Our findings suggest the presence of a high bone turnover state in endemic skeletal fluorosis irrespective of other variables.

Adolescent↗
PubMed1993

Bioavailability and absorption kinetics of nicotine following application of a transdermal system.

1. The absolute bioavailability and absorption kinetics of nicotine were investigated in 13 healthy adult male smokers following single and multiple applications of a nicotine transdermal system (NTS), designed to release nicotine at an approximate rate of 1.5 mg h-1 over 24 h. The absorption of nicotine from the single NTS application was calculated with reference to a simultaneous intravenous infusion (i.v.) of deuterium-labelled nicotine. 2. The mean input time (MIT) and mean absorption time (MAT) for nicotine following application of NTS for 24 h were 7.7 and 4.2 h, respectively. 3. Following NTS removal, the mean apparent nicotine elimination half-life was 2.8 h, compared with 2.0 h following i.v. nicotine, reflecting continued absorption of nicotine following NTS removal. 4. The mean amount of nicotine absorbed from the NTS after the 24 h application was 20.9 mg, which represents about 68% of the amount released from the system; the remaining 32% was lost from the system during daily activities. 5. The ratio of AUC values for the metabolite cotinine relative to nicotine was similar whether nicotine was administered transdermally or intravenously. 6. Following i.v. administration, the mean nicotine clearance was 72 l h-1 (coefficient of variation 29%). Since coefficients of variation in AUC values following NTS and i.v. treatments were similar, transdermal administration of nicotine was not associated with increased interindividual variability in plasma nicotine concentrations. 7. No significant changes were seen in the pharmacokinetics of nicotine between single and multiple applications of NTS. 8. As expected from the higher total plasma nicotine concentrations, the incidence of adverse effects was higher following simultaneous intravenous and transdermal administration of nicotine. The most frequently reported systemic side effects were nervousness and headache: mild itching was the most frequent topical effect.

Administration, Cutaneous↗
PubMed1993

Cranio-metaphyseal dysplasia.

Cranio-metaphyseal dysplasia in two brothers, aged fourteen and twelve, is reported. Both brothers presented with deafness, repeated episodes of cold and cough and mouth breathing. Striking craniofacial configuration consisted of hypertelorism, prominent glabella and zygomatic arches, mandibular prognathism and overgrowth of middle third of face. Both patients had genu valgum deformity. Low intelligence and poor scholastic performance present in both brothers were attributed to deafness. Radiographic features consisted of obtuse mandibular angle, defective dentition, sclerotic frontal sinuses, sclerotic mastoids and temporal bones. Splaying of metaphyses of long bones was associated with mild sclerosis. Mild degree of widening of ribs was also present. One brother also had hallux valgus deformity. The radiographic and clinical differentiation of cranio-metaphyseal dysplasia and metaphyseal dysplasia (Pyle's disease) is highlighted.

Adolescent↗
PubMed1993

Uterocutaneous fistula.

Fistulous communications of the uterus are relatively unknown. We report in this paper the first case to our knowledge of uterocutaneous fistula which developed following a septic abortion induced by introduction of Laminaria tent into the uterus.

Abortion, Septic↗
PubMed1993

Effect of cardiac-locomotor coupling on the metabolic efficiency of pedalling.

Coupling between cardiac and locomotor rhythms (CLC) has been reported while subjects exercise at cadences that are natural to them. The hypothesis that oxygen consumption (VO2) would be lower when subjects pedalled at the rate producing 1:1 coupling of heart and pedalling rates than when they pedalled at noncoupled rates was tested with 12 men on a cycle ergometer. At a moderate power output based on their VO2max, subjects pedalled at six different pedalling rates while VO2 and heart rate were measured. The pedalling rates were the preferred frequency, frequencies 15 and 30% above and below the preferred frequency, and the 1:1 coupled frequency. In 8 of the 12 subjects it was possible to fit their data with significant regression equations relating VO2 to pedalling rate, but in no subject was the 1:1 coupled state energetically beneficial, suggesting that any functional significance of CLC is unrelated to metabolic efficiency.

Adult↗