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Biomedical subjects

J Nandi

Publications and source records attributed to J Nandi.

At least 37 records · Page 2Linked to original sources

Chloroquine versus amodiaquine in the treatment of Plasmodium falciparum malaria in northeast India.

Amodiaquine is being used in India for presumptive treatment as an alternative to chloroquine in areas with chloroquine resistant P. falciparum. Keeping in view the toxicity of amodiaquine, studies have been undertaken to evaluate the advantage of the drug over chloroquine in the treatment of P. falciparum malaria. In vivo drug resistance studies were carried out in the states of Assam and Meghalaya in India. A total of 388 subjects have been studied to compare the efficacy of chloroquine and amodiaquine. The overall cure rate, degree of resistance, mean parasite clearance time and mean parasite recrudescence time were comparable for both the drugs, the differences being not statistically significant. The results indicate no advantage of amodiaquine in the treatment of patients with P. falciparum infection in chloroquine resistant areas of northeast India and development of cross resistance in P. falciparum to these 4-aminoquinolines is complete and parallel.

Adolescent↗

Status of chloroquine resistance in Plasmodium falciparum in Tripura.

In-vivo chloroquine resistance studies on P. falciparum were conducted in 1981 and 1988 in South district of Tripura. Resistance status to chloroquine has been gradually changing over the seven years period. A single case at RIII level was detected in 1988, and RI level of resistance had shown a increasing trend.

Adolescent↗

A possible role of protein kinase C in augmenting H+ secretion by nonsteroidal anti-inflammatory drugs.

The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on H+ secretion were studied in frog gastric mucosa and rabbit parietal cells (PC). In frog gastric mucosa, aspirin (10(-5) M) and ibuprofen (10(-4) M), but not indomethacin, naproxen and carprofen (10(-4) M each), enhanced histamine- and dibutyryl adenosine 3',5'-cyclic monophosphate-stimulated H+ secretion by 20 to 34%. Similarly, a protein kinase C (PKC) inhibitor, 1-(5-isoquinolinesulfonyl)- 2-methyl piperazine (H7, 5 x 10(-5) M), and a calcium ionophore, A23187 (10(-6) M) augmented basal and the aforementioned secretagogue-stimulated H+ secretion by approximately 50% and 20%, respectively, but a PKC activator, phorbol ester (12-O-tetradecanoyl phorbol 13-acetate, 10(-7)-10(-6) M), had no effect. The augmentation of H+ secretion by these agents was blocked by a calcium antagonist, lanthanum chloride (5 x 10(-4) M). In rabbit PC, H7 augmented secretagogue-stimulated H+ secretion by 60 to 150%, whereas 12-O-tetradecanoyl phorbol 13-acetate (10(-7) M) inhibited carbachol- and histamine-stimulated H+ secretion, respectively, by 65% and 52% without affecting dibutyryl adenosine 3',5'-cyclic monophosphate-stimulated H+ secretion. Furthermore, NSAIDs and H7-induced augmentation of dibutyryl cyclic adenosine monophosphate-stimulated H+ secretion was prevented by 12-O-tetradecanoyl phorbol 13-acetate (10(-7)-10(-6) M) in frog gastric mucosa and rabbit PC. Unlike H7, NSAIDs had no direct inhibiting action on PC membrane or cytosolic fractions of PKC, but they inhibited Sn-1,2-diacylglycerol level in PC by 20 to 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Alternative mode of replication of human immunodeficiency virus: a hypothesis.

For diagnosis of Human Immunodeficiency Virus (HIV) infection by the recently developed Polymerase Chain Reaction (PCR), the two commonly used clinical samples are either the peripheral blood monocytes (PBMC) or the plasma of the infected individuals. In the former instance, DNA is extracted from PBMC. The integrated proviral DNA is then amplified using HIV specific oligonucleotide primers. In the latter instance, RNA is extracted from plasma. This is reverse transcribed in vitro into cDNA by using extraneous reverse transcriptase. This cDNA is then used as a target in PCR experiments with HIV specific primers. In contrast we have recently used DNA directly extracted from plasma of infected individuals. This DNA was used for amplification of HIV genome with primer pairs specific for HIV. An interesting outcome of this study was a model to explain the presence of DNA of HIV in the plasma. We suggest that possibly there is an alternative mode of replication of HIV. Apart from the obligatory integration of the DNA of HIV into the DNA of lymphocytes as provirus, several additional copies of the DNA are also made which remain unintegrated. These probably exist as a housekeeping repertoire of the viral genome. These DNA molecules may be released into the circulation along with the newly formed mature virion particles during the usual course of replication and release of the virus. In our experiments with direct extraction of DNA from plasma, these unintegrated DNA of HIV may act as the target for PCR to give positive signals with HIV specific primers.

DNA, Viral↗

Present perspectives of malaria transmission in Boko area of Assam.

A longitudinal study on malaria transmission was conducted from January 1984 to December 1988 in three villages in Boko PHC of Assam, where indoor residual DDT spray was withdrawn during the period of study. Anopheline fauna comprising of 19 species was identified and their seasonal density estimated. Anopheles philippinensis was the predominant species followed by An. minimus. The principal role of An. minimus in the transmission of malaria and predilection for indoor resting in this area was clearly evident. Though An. dirus and An. fluviatilis were found in low density, sporozoite infection was detected in them along with An. minimus. The high malaria incidence predominantly with Plasmodium falciparum was closely related to sporozoite infection in the vectors and their densities. The biting cycle of An. minimus was maximum in the first half of the night.

Animals↗

Malaria transmission in Nagaland, India. Part-I--Anophelines and their seasonality.

A longitudinal study on malaria transmission was conducted from January 1983 to December 1988 in two villages of Dimapur PHC in Nagaland. A diverse anopheline fauna comprising of 23 species was identified including three species viz. An. aitkeni, An. bengalensis and An. insulaeflorum which were observed in larval stages only. An. vagus was the predominant species followed by An. philippinensis, An. culicifacies and An. minimus. An. minimus though maintained relatively high density throughout the year manifested two peaks in June and October. An. fluviatilis and An. dirus though found in relatively low density their seasonal prevalence was suggestive of a post-monsoon and monsoon species respectively.

Animals↗

Nonsalicylate nonsteroidal antiinflammatory drugs augment prestimulated acid secretion in rabbit parietal cells. Investigation of the mechanisms of action.

The effects of nonsalicylate nonsteroidal antiinflammatory drugs on acid secretion were studied in isolated rabbit parietal cells. Indomethacin, naproxen, and carprofen (10(-6)-10(-4) mol/L) potentiated histamine-, forskolin-, 3-isobutyl-1-methylxanthine-, and dibutyryl cyclic adenosine monophosphate-stimulated acid secretion without affecting basal acid secretion. This augmentation of secretagogue-stimulated acid secretion was dependent on extracellular calcium because potentiation was abolished by calcium depletion of the medium or in the presence of the calcium antagonist lanthanum chloride. Potentiation was independent of the H2 and muscarinic receptors and did not appear to involve guanine nucleotide regulatory proteins. Proton pump activity was unaffected by indomethacin. Furthermore, nonsteroidal antiinflammatory drugs increased calcium efflux through the plasma membrane, as measured by calcium 45, and decreased endogenous prostaglandin E2 content. Exogenous dimethyl prostaglandin E2 inhibited the potentiating effect of these drugs on histamine-stimulated but apparently not on dibutyryl cyclic adenosine monophosphate-stimulated acid secretion. The data indicate that nonsalicylate nonsteroidal antiinflammatory drugs interacted at a postreceptor site between adenylate cyclase and the proton pump. The potentiating effects of these drugs were regulated by calcium and possibly modulated by prostanoids.

Animals↗

Aspirin potentiates prestimulated acid secretion and mobilizes intracellular calcium in rabbit parietal cells.

The effects of aspirin on gastric acid secretion were studied in isolated rabbit parietal cells (PC). Aspirin (10(-5) M) potentiated histamine-, dibutyryl cyclic AMP (dbcAMP)-, forskolin- and 3-isobutyl-1-methylxanthine-stimulated acid secretion without affecting basal acid secretion. Augmentation of secretagogue-stimulated acid secretion by aspirin was dependent on calcium (Ca2+) since potentiation was blocked by removal of extracellular Ca2+ ([Ca2+]o) or addition of the calcium antagonist lanthanum chloride. Using the Ca2+ probe fura-2, aspirin (10(-6) - 2 X 10(-5) M) rapidly increased intracellular free Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. The source of released Ca2+ was intracellular as demonstrated by depletion of intracellular Ca2+ and [Ca2+]o with EGTA washing. Aspirin did not affect several other signal transduction sites involved in stimulus-secretion coupling, including the H2 receptor, intracellular cyclic AMP (cAMP), inositol 1,4,5, triphosphate (IP3) and H+,K(+)-ATPase. Aspirin decreased PC prostaglandin E2 (PGE2) content by 98%. Exogenous dimethyl PGE2 (dmPGE2) inhibited both histamine-stimulated acid secretion and its enhancement by aspirin. In contrast, dmPGE2 abolished aspirin-induced potentiation of dbcAMP-stimulated acid secretion by augmenting the dbcAMP-stimulated response. These results indicate that aspirin acts at a site beyond the adenylate cyclase/cAMP system and before the proton pump, presumably by releasing Ca2+ from an IP3-independent intracellular storage pool and by inhibiting PGE2 generation.

Adenosine Triphosphatases↗

Purification of antigen for serodiagnosis of echinococcosis.

Antigen for serodiagnosis of Echinococcosis is purified by chromatography on DEAE-Cellulose and Sephadex G-200 from hydatid cyst fluid. The antigen is electrophoretically pure and found sensitive and specific for Echinococcus granulosus. The antigen is thermostable and is apparently a lipo protein.

Animals↗

Mechanisms of gastric proton pump inhibition by calcium channel antagonists.

The inhibitory effects of Ca channel antagonists on gastric acid secretion [[14C]-aminopyrine (AP) uptake ratio] have been analyzed in isolated rabbit parletal cells (PC). Secretagogue-stimulated AP uptake was inhibited by verapamil and diltiazem in a dose-dependent manner with IC50 values of 15 and 100 microM, respectively, both in the presence and absence of extracellular Ca. In contrast, nifedipine had no effect on AP accumulation. Verapamil decreased histamine-stimulated respiration with the same IC50 as observed for AP uptake. Imidazole, a weak base, by buffering the acid spaces in PC, reversed the inhibitory effect of verapamil on respiration. In the bullfrog gastric mucosa, forskolin-stimulated proton transport was inhibited by verapamil (10(-4) M) from the luminal but not the serosal side. This inhibitory effect was reversed by either elevating KCl concentration in, or removing the drug from, the secretory solution. Verapamil inhibited gastric microsomal H+,K(+)-adenosine triphosphatase (H+,K(+)-ATPase) and PC K(+)-stimulated p-nitrophenyl phosphatase activities with a higher potency than diltiazem. Inhibition of these enzymes by verapamil and diltiazem was pH dependent. The drugs competed with K+ in both H+,K(+)-ATPase and K(+)-stimulated p-nitrophenyl phosphatase reactions. Our data suggest that inhibition of the gastric proton pump by verapamil or diltiazem is not due to their Ca channel antagonism but to their interaction with the luminal high affinity K(+)-site of the H+,K(+)-ATPase under acidic conditions.

Adenosine Triphosphatases↗

Characterization of third beta-chain variant in Rattus rattus rufescens.

Different molecular forms of hemoglobins of locally available murines, represented by Rattus rattus rufescens, have been investigated and the probable genetic mechanisms leading to the observed heterogenicity in the hemoglobin phenotypes are discussed. Each fraction was isolated in chromatographically pure form, identified and characterised structurally to establish their alpha- and non-alpha-chain constitution. Six molecular forms of component hemoglobins were identified from a wild population of R. rattus rufescens. The present study suggests five different globin chains in the hemoglobin of house rats (Rattus rattus rufescens). There are apparently two alpha-chains, namely alpha I and alpha II, and three different beta-chains, viz. beta I, beta II and beta III. The invariable presence, though at varying concentrations, of all these five globin chains implicates a gene duplication at the alpha-chain loci and a gene triplication at the beta-chain loci, the latter being a rather rare and unique genetic event.

Animals↗

Characteristics of the isolated apical plasmalemma and intracellular tubulovesicles of the gastric acid secreting cells: demonstration of secretagogue-induced membrane mobilization.

Separation of the gradient-purified gastric microsome into two membrane subfractions of distinct enzymatic and phospholipid composition has been achieved by mild SDS (0.033% w/v) treatment followed by sucrose gradient centrifugation of the pig and rabbit gastric microsomes. While the high-density membranes had all of the (H+,K+)-ATPase and K+-pNPPase activities and revealed a single major 100-kDa band on SDS-PAGE, the low-density membranes contained all of the 5'-nucleotidase and nearly all of the Mg2+-ATPase. In the present study, the low-density subfraction has been characterized to be derived from the apical membranes and the high-density one from the intracellular tubulovesicular membranes of the parietal cells. Such characterization was based primarily on sole dependency of the apical plasma membranes on the endogenous activator for (H+,K+)-ATPase activity, differential sensitivity of the activator (AF)-dependent and -independent (H+,K+)-ATPase on micromolar vanadate and Ca2+, specific vitamin B12 binding ability of the apical plasmalemma, phospholipid and protein profiles of the two membrane subfractions, and other parameters. The AF, mentioned previously, has recently been implicated as a cytosolic regulator of the gastric (H+,K+)-ATPase [Bandopadhyay et al. (1987) J. Biol. Chem. 262, 5664-5670]. Two different forms (i.e., AF-dependent and -independent forms) of the (H+,K+)-ATPase are suggested to be present in the tubulovesicles on the basis of differential vanadate sensitivity while the AF-dependent form alone is present in the apical membranes. The data have been discussed in terms of stimulation-induced membrane transformation characteristic of the H+-secreting epithelia including the acid-secreting cells of the stomach.

Adenosine Triphosphatases↗

Half of the (Na+ + K+)-transporting-ATPase-associated K+-stimulated p-nitrophenyl phosphatase activity of gastric epithelial cells is exposed to the surface exterior.

Ouabain inhibited 86RbCl uptake by 80% in rabbit gastric superficial epithelial cells (SEC), revealing the presence of a functional Na+,K+-ATPase [(Na+ + K+)-transporting ATPase] pump. Intact SEC were used to study the ouabain-sensitive Na+,K+-ATPase and K+-pNPPase (K+-stimulated p-nitrophenyl phosphatase) activities before and after lysis. Intact SEC showed no Na+,K+-ATPase and insignificant Mg2+-ATPase activity. However, appreciable K+-pNPPase activity sensitive to ouabain inhibition was demonstrated by localizing its activity to the cell-surface exterior. The lysed SEC, on the other hand, demonstrated both ouabain-sensitive Na+,K+-ATPase and K+-pNPPase activities. Thus the ATP-hydrolytic site of Na+,K+-ATPase faces exclusively the cytosol, whereas the associated K+-pNPPase is distributed equally across the plasma membrane. The study suggests that the cell-exterior-located K+-pNPPase can be used as a convenient and reliable 'in situ' marker for the functional Na+,K+-ATPase system of various isolated cells under noninvasive conditions.

4-Nitrophenylphosphatase↗

Effects of nonsteroidal, antiinflammatory drugs on gastrointestinal injury and prostanoid generation in healthy volunteers.

A new nonsteroidal, antiinflammatory drug, carprofen, was compared with indomethacin as to their effects on mucosal injury and prostanoid biosynthesis. A prospective, double-blind endoscopy study was performed in 40 healthy adults. After baseline normal endoscopy, 20 subjects were randomly assigned to either indomethacin (25 mg four times daily) or carprofen (150 mg twice daily) for eight days and re-endoscoped. Urinary and gastric mucosal prostaglandin generation, respectively, of PGE2 and PGF2 alpha, and PGE and 6-keto-PGF1 alpha was determined. Minor subjective symptoms occurred in six of 20 indomethacin (including four of eight with gastrointestinal injury) and in three of 20 carprofen subjects. Indomethacin and carprofen reduced gastric and urinary prostaglandin synthesis to a similar degree. Gastrointestinal injury was present in eight of 20 indomethacin and in none of 20 carprofen subjects. This study fails to establish a relationship between duodenal mucosal lesions and gastric prostanoid generation and confirms the lack of correlation between indomethacin-induced duodenal injury and subjective symptomatology. Carprofen appears to produce less objective damage in the upper gastrointestinal tract than indomethacin at comparable clinical doses.

Anti-Inflammatory Agents, Non-Steroidal↗

Effects of ethanol on parietal cell membrane phospholipids and proton pump function.

The effects of ethanol on membrane phospholipids of isolated rabbit parietal cells (PC) and fundic glands (FG) were evaluated by using proton nuclear magnetic resonance spectroscopy (NMR). The most conspicuous resonance bands in PC and FG spectra at 3.2 and 0.9 ppm were due to the protons of +N(CH3)3 groups of phosphatidylcholine and, to a lesser degree, other phospholipid derivatives and terminal -CH3 groups for all phospholipids, respectively. Ethanol treatment (1 min) of PC and FG at 37 degrees C significantly increased the peak intensity of -CH3 groups in a dose-dependent manner, while no intensity change in PC and a lesser change in FG were observed for the +N(CH3)3 groups, suggesting a greater disorganizing effect of ethanol in the inner hydrophobic (-CH3) compared with the outer hydrophilic [+N(CH3)3] membrane moieties of phospholipids. Ethanol at concentrations greater than 5% (vol/vol) inhibited K+-stimulated paranitrophenyl phosphatase activity of intact PC, which correlated with inhibition of basal and histamine-stimulated aminopyrine uptake ratio by PC and FG. NMR is a sensitive, noninvasive probe to show ethanol-induced changes in intact PC lipid membrane organization without altering ultrastructural morphology.

Adenosine Triphosphatases↗

Purification and partial characterization of the (H+,K+)-transporting adenosinetriphosphatase from fundic mucosa.

The microsomal (H+,K+)-ATPase systems from dog and pig fundic mucosa were purified to homogeneity and partially characterized. The method involves sodium dodecyl sulfate (SDS) (0.033% w/v) extraction of the microsomal non-ATPase proteins under appropriate conditions followed by sucrose density gradient centrifugation. Two distinct membrane bands of low (buoyant density = 1.08 g/mL) and high (buoyant density = 1.114 g/mL) densities having distinct enzymatic and chemical composition were harvested. The low-density membrane was highly enriched in Mg2+- or Ca2+-stimulated ATPase and 5'-nucleotidase activities but totally devoid of (H+,K+)-ATPase and K+-p-nitrophenylphosphatase activities. The latter two activities were found exclusively in the high-density membrane. SDS-polyacrylamide gel electrophoresis revealed the high-density membranes to consist primarily of a major 100-kilodalton (kDa) protein and a minor 85-kDa glycoprotein, the former being the catalytic subunit of the (H+,K+)-ATPase. The amino acid composition of the pure dog (H+,K+)-ATPase revealed close similarities with that from pig. The N-terminal amino acid was identified to be lysine as the sole residue. Similar to the high-density membrane-associated pure (H+,K+)-ATPase, the low-density membranes containing high Mg2+-ATPase activity also contained a 100-kDa peptide and a 85-kDa glycopeptide in addition to numerous low molecular weight peptides. Also, similar to the pure (H+,K+)-ATPase, the Mg2+-ATPase-rich fraction produced an E approximately P unstable to hydroxylamine and partially (about 25%) sensitive to K+ but having a slow turnover. The levels of E approximately P produced by the pure (H+,K+)-ATPase- and Mg2+-ATPase-rich fractions were 1400 and 178 pmol/mg of protein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

Characteristics of a pure endogenous activator of the gastric H+,K+-ATPase system. Evaluation of the role as a possible intracellular regulator.

An endogenous activator capable of stimulating the gastric H+,K+-ATPase activity has been purified to homogeneity from dog and pig gastric cells and found to be a dimer of two identical 40-kDa subunits in the active state. Identical nature of the activator monomers was revealed by the detection of lysine as the sole N-terminal amino acid. The activator from one species can stimulate the H+,K+-ATPase from another species and vice versa. Such cross-activation is consistent with the striking similarities in the amino acid composition between the two species, suggesting considerable homology in the activator molecules from different species. The activator exhibited several unique features during modulation of the H+,K+-ATPase reaction. It appreciably enhances affinity of the H+,K+-ATPase for K+, known to increase turnover of the enzyme. To complement this K+ affinity, the activator also enhances ability of the H+,K+-ATPase to generate more transition state (E*.ATP) complex by increasing the entropy of activation (delta S++) of the system as revealed from an Arrhenius plot of the data on temperature activation. In addition, the activator shows both positive cooperativity and strong inhibition, depending on its concentration. Thus, up to the ratio of the H+,K+-ATPase and activator of about 1:2 (on the protein basis), the activator shows sigmoidal activation (Hill coefficient = 4.5), but beyond such concentration a strong inhibition was observed. Finally, Ca2+ at low (2-4 microM) concentration strongly inhibits the activator-stimulated H+,K+-ATPase. It is proposed that the activator may be acting as a link in the signal transducing cascade system between the intracellular second messenger (Ca2+) and the physiological response (gastric H+ transport).

Adenosine Triphosphatases↗