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Biomedical subjects

S Trivedi

Publications and source records attributed to S Trivedi.

At least 37 records · Page 2Linked to original sources

Acupressure treatment for prevention of postoperative nausea and vomiting.

Postoperative nausea and vomiting are still common problems after general anesthesia, especially in ambulatory surgery. Drug therapy is often complicated with central nervous system symptoms. We studied a nonpharmacological method of therapy--acupressure--at the Pericardium 6 (P.6) (Nei-Guan) meridian point. Two hundred consecutive healthy patients undergoing a variety of short surgical procedures were included in a randomized, double-blind study: 108 patients were in the acupressure group (Group 1) and 92 patients were in the control group (Group 2). Spherical beads of acupressure bands were placed at the P.6 points in the anterior surface of both forearms in Group 1 patients, while in Group 2 they were placed inappropriately on the posterior surface. The acupressure bands were placed before induction of anesthesia and were removed 6 h postoperatively. They were covered with a soft cotton wrapping to conceal them from the blinded observer who evaluated the patients for presence of nausea and vomiting and checked the order sheet for any antiemetics prescribed. In both groups, the age, gender, height, weight, and type and duration of surgical procedures were all comparable without significant statistical difference. In Group 1, only 25 of 108 patients (23%) had nausea and vomiting as compared to Group 2, in which 38 of 92 patients (41%) had nausea and vomiting (P = 0.0058). We concluded that acupressure at the P.6 (Nei-Guan) point is an effective prophylaxis for postsurgical nausea and vomiting and therefore a good alternative to conventional antiemetic treatment.

Acupressure↗

Expression and characterization of inactivating and activating mutations in the human Ca2+o-sensing receptor.

Nearly 30 mutations have been identified to date in the coding region of the extracellular calcium-sensing receptor (CaR) that are associated with inherited human hypo- and hypercalcemic disorders. To understand the mechanisms by which the mutations alter the function of the receptor may help to discern the structure-function relationships in terms of ligand-binding and G protein coupling. In the present studies, we transiently expressed eight known CaR mutations in HEK293 cells. The effects of the mutations on extracellular calcium- and gadolinium-elicited increases in the cytosolic calcium concentration were then examined. Seven inactivating mutations, which cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism, show a reduced functional activity of the receptor because they may 1) reduce its affinity for agonists; 2) prevent conversion of the receptor from a putatively immature, high mannose form into the fully glycosylated and biologically active form of the CaR, in addition to lowering its affinity for agonists; or 3) fail to couple the receptor to and/or activate its respective G protein(s). Conversely, one activating mutation, which causes a form of autosomal dominant hypocalcemia, appears to increase the affinity of the receptor for its agonists.

Blotting, Western↗

Tamoxifen aziridine labeling of the estrogen receptor-potential utility in detecting biologically aggressive breast tumors.

Expression of estrogen receptor (ER) is a helpful predictor of response to endocrine therapy and disease free survival in breast cancer patients. The presence of variant estrogen receptors has been demonstrated at the RNA/DNA level and might represent an escape of tumors from hormonal control mechanisms. However, the demonstration that the corresponding peptides do exist is a real challenge. Denaturing polyacrylamide gel electrophoresis (SDS-PAGE) of covalently bound [3H]tamoxifen aziridine ([3H]TAZ) to ER demonstrates a specific, multiband peptide pattern recognized by anti-ER monoclonal antibodies (anti-ER Mo Abs). The native 66 kDa ER form identified through its hormone binding domain by the H-222 Mo Ab was the most prominent one followed by 50, 35, and 28 kDa forms on fluorography. Such patterns from early human breast tumors were compared to the ones of more advanced disease, namely large primary breast cancers, metastatic lymph nodes, and soft tissue relapses: in these cases, molecular forms of 43 and 35 kDa were identified with a remarkable consistency. The 43 kDa peptide was more frequently identified by the H-226 Mo Ab (which maps a region near the DNA binding domain)-albeit with low labeling intensity as compared to H-222 Mo Ab. In addition, the 43 kDa peptide was inversely correlated to ER levels. This altered ER or related peptide could potentially be a marker of biologically aggressive breast tumors.

Antibodies, Monoclonal↗

Calcium dependent K-channels in guinea pig and human urinary bladder.

This study provides evidence for the presence of large conductance Ca(2+)-dependent K-channels in guinea pig and human urinary bladder smooth muscle. A23187, a Ca(2+)-ionophore, increased charybdotoxin and iberiatoxin sensitive 42K efflux in human urinary bladder smooth muscle cells, suggesting that large conductance Ca(2+)-dependent K-channels are present in these cells. NS004, a large conductance Ca(2+)-dependent K-channel opener, relaxed guinea pig bladder strips precontracted with 15 mM KCl which is inhibited by iberiatoxin. In addition, NS004 also evoked an iberiatoxin sensitive increase in 86Rb/42K efflux in guinea pig and human urinary bladder smooth muscle cells, demonstrating that NS004 activates large conductance Ca(2+)-dependent K-channels to achieve its relaxation effect in the bladder.

Animals↗

K-channel opening activity of ZD6169 and its analogs: effect on 86Rb efflux and 3H-P1075 binding in bladder smooth muscle.

Zeneca ZD6169, (S)-N-(4-benzoylphenyl)-3,3,3-trifluoro- 2-hydroxy-2-methylpropionamide, is a novel compound which relaxes urinary bladder smooth muscle in vitro. The effect of ZD6169 and two of its analogs on 86Rb efflux and 3H-P1075 binding in guinea pig bladder strips was investigated to characterize the K-channel opening properties of this compound. ZD6169 concentration dependently increased the rate of 86Rb efflux from guinea pig bladder strips. 86Rb efflux evoked by ZD6169 and its analogs was blocked by glibenclamide (30 muM) but not by charybdotoxin, apamin or alpha-dendrotoxin, suggesting that this compound activates KATP channels in guinea pig bladder. In addition, interaction of ZD6169 with KATP channels was also confirmed in human bladder smooth muscle cells. Specific binding of 3H-P1075, a potent opener of KATP channels, to guinea pig urinary bladder strips was observed. 3H-P1075 binding was inhibited by known KATP openers. ZD6169 inhibited binding of 3H-P1075 to urinary bladder strips like other structurally different KATP openers, e.g. cromakalim and pinacidil. Potencies for inhibition of 3H-P1075 binding by ZD6169 and other potassium channel openers correlate well with potencies for increase in 86Rb efflux and bladder muscle relaxation studies. It is concluded that Zeneca ZD6169 is a potassium channel opener which activates ATP-sensitive K-channels in guinea pig urinary bladder strips as well as in human bladder cells. Furthermore, binding studies suggest that the effects of ZD6169 and its analogs are mediated by binding to the site labeled by 3H-P1075 in guinea pig bladder strips.

Amides↗

K-channel opening activity of dihydropyridine ZM244085: effect on 86Rb efflux and 3H-P1075 binding in urinary bladder smooth muscle.

Zeneca ZM244085, 9-(3 cyanophenyl)hexahydro-1,8 acridinedione, is a novel dihydropyridine (DHP) which relaxes KCl precontracted urinary bladder smooth muscle in vitro. The effect of ZM244085 on low and high KCl induced contractions, 86Rb efflux and [3H]-P1075 binding in guinea pig bladder strips was investigated to characterize the K-channel opening properties of this compound. Since ZM244085 is a dihydropyridine its effect on DHP binding sites on Ca2+ channels was also investigated. ZM244085 was found to be more potent in relaxing detrusor strips precontracted with 15 mM KCl than strips precontracted with 80 mM KCl (Li et al., 1995). This functional profile of ZM244085 is similar to that exhibited by typical K-channel openers (PCO). In addition, inhibition of ZM244085 induced relaxation of detrusor strips by glibenclamide suggests that ZM244085 opens ATP sensitive K-channel (KATP) in urinary bladder (Li et al., 1995). Since the glibenclamide sensitive smooth muscle relaxation activity of ZM244085 could still be an indirect effect of this compound on KATP channels we carried out 86Rb efflux studies and [3H]-P1075 binding studies to further confirm these findings. The 86Rb efflux assay is a direct method for monitoring the movement of K+ ions across the cell membranes. Displacement of [3H]-P1075 binding to bladder membranes supports a direct action of the compound on the KATP channel. The present study demonstrates that ZM244085 in a concentration dependent manner increases the rate of 86Rb efflux from guinea pig bladder strips. This effect was inhibited by glibenclamide (30 microM), a known KATP channel blocker. In addition, interaction of ZM244085 with KATP channels was also confirmed in human bladder smooth muscle cells using a 42K efflux assay. Furthermore, we were able to demonstrate that ZM244085, structurally distinct PCO, inhibited the binding of 3H-P1075 to urinary bladder strips in a manner similar to other KATP openers such as cromakalim and pinacidil. Inhibition of 3H-P1075 binding by ZM244085 and other PCO's correlates well with increases in 86Rb efflux and bladder muscle relaxation studies. Finally, ZM244085 did not exhibit any significant affect on VSCC as evidenced by very weak inhibition of [3H]-PN200,110 binding to bladder membranes by ZM244085. It is concluded that Zeneca ZM244085 is a PCO which activates KATP channels in urinary bladder.

Acridines↗

Major molecular weight heterogeneity of estrogen receptor from breast cancer is not related to neoplasia.

Recent investigation from our laboratory revealed that the estrogen receptor (ER) from breast cancer is characterized by a high molecular weight polymorphism: SDS-polyacrylamide gel electrophoresis of [3H]-tamoxifen aziridine ([3H]-TAZ) labeled cytosols usually display several bands corresponding to the native receptor (67 KDa) and lower molecular cleavage products. High frequency of such altered receptors was confirmed here by size exclusion FPLC of [125I]-E2 labeled cytosols from a series of 98 breast cancers: on the average, 60% of the ER molecules were strongly degraded (Mr < or = 37 KDa). The absence of transcriptional activating domains (ABC domains) in such receptors was further demonstrated by assessing their ability to bind to hydroxylapatite (HAP). Thus, in presence of 500 mM KCI, 55% of ERs from another series of 54 cytosols failed to strongly adsorb to this phosphocalcic matrix, a characteristic property of receptors without exposed ABC domains. Finally, [3H]-TAZ labeled cytosols from normal uterine tissue and MCF-7 human breast cancer cells growing in nude mice displayed identical multibands electrophoretic patterns revealing in both cases native and cleaved receptors. Since latter receptor forms were never detected in MCF-7 cells growing in monolayer culture, we put forward the hypothesis that they were produced under the action of proteolytic enzymes acting at the time of tissue processing. Hence, most of the truncated receptors detected in human breast cancer cytosols should not be markers of malignancy.

Animals↗

Utilization of ICDS scheme in children one to six years of age in a rural block of central India.

The evaluation of nutritional and immunization services was undertaken in the rural ICDS block Sanwer (Madhya Pradesh) where the project is functioning from last 3 years. A door to door survey was conducted in 1993 in six Anganwadi areas in ICDS block and five randomly selected matched non ICDS rural area served as controls. There were a total of 709 children in ICDS and 500 in non ICDS block in 1-6 years age group. The difference was not statistically significant for nutritional status in the two blocks, but a remarkably better immunization status (p < 0.005) was observed in non ICDS block. The coverage for DPT (3 doses), and measles vaccination in ICDS block was 79.57% and 45.7%, respectively, while in non ICDS block it was 94.4% and 62.03%, respectively. It seems the ICDS scheme is under utilized by the community and requires immediate attention by the health authorities.

Child Nutritional Physiological Phenomena↗

Effect of cromakalim and pinacidil on 86Rb efflux from guinea pig urinary bladder smooth muscle.

86Rb efflux assay was used to investigate the effect of cromakalim, pinacidil and P1075 in guinea pig urinary bladder strips. The type of K channel opened by cromakalim and pinacidil was determined using specific K channel blockers through 86Rb efflux assay in detrusor strips. Cromakalim, pinacidil and P1075 all three potassium channel openers (PCOs) evoked a concentration-dependent increase in 86Rb efflux in bladder strips. This increase in isotope release was inhibited by pretreatment of bladder with 10 and 30 microM glibenclamide suggesting that both cromakalim and pinacidil interact with ATP-sensitive K channels (KATP). Further, an increase in basal 86Rb efflux was observed when 2-deoxy-D-glucose was substituted for glucose together with 0.24 micrograms/ml of oligomycin (known to lower intracellular ATP) indicating the presence of KATP channels in bladder smooth muscle. Charybdotoxin and apamin, blockers of large and small conductance Ca(2+)-dependent K channels, were found not to be involved in the action of these PCOs in bladder strips. alpha-Dendrotoxin, known to block voltage-dependent K channels, slightly reduced pinacidil-induced 86Rb release without affecting cromakalim-induced 86Rb efflux. The present studies show that ATP-sensitive K channels are present in guinea pig urinary bladder and that cromakalim and pinacidil act by opening these ATP-sensitive K channels in detrusor strips.

Adenosine Triphosphate↗

Characterization of ATP-sensitive potassium channel-blocking activity of ZENECA ZM181,037, a eukalemic diuretic.

ZENECA ZM181,037 is a novel eukalemic diuretic from a series of 1,1-diarylcarbin-1-01-2 amines. In contrast to the standard diuretic hydrochlorothiazide, the blood pressure-lowering effect was not observed with ZENECA ZM181,037 in spontaneously hypertensive rats. ZENECA ZM181,037 demonstrated a K+ channel-blocker profile. In the isolated rat aorta stimulated with 20 mmol/l KCl, both the d- and l-enantiomer of ZENECA ZM181,037 antagonized the relaxation of cromakalim with mean pKB values of 6.4 and 6.7, respectively. In the isolated guinea-pig portal vein and urinary detrusor muscle, both enantiomers enhanced the spontaneous myogenic activity at concentrations of 1 mumol/l and higher, in addition to antagonizing the effect of cromakalim. ZENECA ZM 181,037, similar to glibenclamide, prevented a significant increase in 86Rb+ by cromakalim in both portal vein and detrusor muscle strips; however, ZENECA ZM181,037, dissimilar to glibenclamide and tolbutamide, did not increase plasma glucose when given orally to dogs. Thus, ZENECA ZM181,037 is a blocker of the ATP-sensitive K+ channel (KATP) in vascular and nonvascular tissues. In view of the profound saluresis produced by ZENECA ZM181,037, the lack of antihypertensive effect appears to result from its blocking activity on KATP in vascular tissues.

Acetamides↗

Multi-phasic Questionnaire profile of alcoholics and related factors.

Thirty alcoholics treated as inpatients were administered the Multi-phasic Questionnaire (MPQ), a short version of MMPI, to study their personality pattern. Results showed highest loading on depression (85%) and lowest on anxiety (3%). A significant correlation was found between scales of psychopathic deviance and hysteria. Age of problem drinking under 35 years and poor PQ level were found to be associated with depression and psychopathic deviance. Clinical diagnosis was corroborated by the findings of the MPQ. The findings of the present study may be utilised to screen adolescents from alcoholic families for preventive measures.

Adult↗

The synergistic effect of drought and light stresses in sorghum and pearl millet.

The effects of drought stress and high irradiance and their combination were studied under laboratory conditions using young plants of a very drought-resistant variety, ICMH 451, of pearl millet (Pennisetum glaucum) and three varieties of sorghum (Sorghum bicolor)-one drought-resistant from India, one drought-tolerant from Texas, and one drought-sensitive variety from France. CO(2) assimilation rates and photosystem II fluorescence in leaves were analyzed in parallel with photosynthetic electron transport, photosystem II fluorescence, and chlorophyll-protein composition in chloroplasts isolated from these leaves. High irradiance slightly increased CO(2) assimilation rates and electron transport activities of irrigated plants but not fluorescence. Drought stress (less than -1 megapascal) decreased CO(2) assimilation rates, fluorescence, and electron transport. Under the combined effects of drought stress and high irradiance, CO(2) assimilation rates and fluorescence were severely inhibited in leaves, as were the photosynthetic electron transport activities and fluorescence in chloroplasts (but not photosystem I activity). The synergistic or distinctive effect of drought and high irradiance is discussed. The experiments with pearl millet and three varieties of sorghum showed that different responses of plants to drought and light stresses can be monitored by plant physiological and biochemical techniques. Some of these techniques may have a potential for selection of stress-resistant varieties using seedlings.

Journal Article↗

Cognitive functioning of alcoholics and its relationship with prognosis.

In a preliminary study a group of 30 alcoholics were subjected to psychological tests to explore the influence of regular alcohol intake on their cognitive functioning and its relationship with prognosis. The functions chosen were, arousal and maintenance of attention, verbal intelligence and performance intelligence. Tests used were the Binet Kamat test of intelligence and Bhatia short scale. Level of education was positively correlated with attention-span and verbal intelligence, but not with performance intelligence. The inter-test discrepancy alone on the performance intelligence test could be assessed for evaluation of cognitive impairment. Poor P.Q. scorers sought medical consultation before their mid thirties and had earlier onset of alcoholism. Elder addicts (above 35 years) showed more abstraction deficiency. The higher the P.Q. the higher was its' positive correlation with adjustment to work, but not to family.

Adult↗

Pharmacologic experiments on the interaction between crotoxin and the mammalian neuromuscular junction.

Crotoxin and its two subunits were tested for their neuromuscular blocking activity on the phrenic nerve-hemidiaphragm preparation. Two types of experimental paradigms were used, the first of which separated the toxin binding step from subsequent events in paralysis and the second of which did not. In both paradigms the toxin produced concentration-dependent blockade of transmission. However, the results with low concentrations were variable, and in some cases complete neuromuscular blockade did not develop. The isolated acidic and basic subunits possessed little toxicity. In experiments designed to characterize binding, the intact toxin displayed the following properties: 1) the apparent half-time for tissue association was about 22 min; 2) binding was not affected by low temperature, the presence or absence of nerve stimulation and the substitution of strontium for calcium; and 3) when binding was allowed to go to completion, reversibility was negligible. Pretreatment of tissues with the isolated subunits of crotoxin did not enhance or inhibit the binding of the parent molecule. Modification of one histidine residue in the isolated basic subunit, followed by reconstitution with unmodified acidic subunit, generated a molecule that possessed only about 10% of the neurotoxicity of the native toxin. The modified toxin could not be used to antagonize binding of the native toxin. Both polyclonal and monoclonal antibodies were generated that neutralized the biologic activity of crotoxin. In experiments that separated the binding step from later events in paralysis, the polyclonal preparation continued to locate and partially neutralize tissue-bound toxin. In experiments that initiated events that follow binding, polyclonal antibodies were progressively less effective with time in neutralizing toxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Discrete charge carrier transfer sites on proteins? A D.C. conductivity study on ultrathin protein films.

D.C. electrical conduction in thin protein films (200 mg/cm2; approximately 2 mu in thickness) of bovine serum albumin and its dinitrophenylated derivatives with different stoichiometric composition was investigated at 17, 20 and 23% relative humidities and at room temperature. Statistically significant decrease in conductivity due to derivatization was observed even at protein-2,4-dinitrophenol stoichiometry as low as 1:2. A charge injection mechanism based upon discrete charge carrier transfer sites could account for the observations. Analogous events may operate in cellular signaling and coding.

Animals↗