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Biomedical subjects

S K Aggarwal

Publications and source records attributed to S K Aggarwal.

At least 19 recordsLinked to original sources
PubMed1992

Determination of cobalt in urine by gas chromatography-mass spectrometry employing nickel as an internal standard.

A gas chromatographic-mass spectrometric method for the determination of cobalt in biological materials employing stable enriched 62Ni as an internal standard and using lithium bis(trifluoroethyl)dithiocarbamate as a chelating agent is described. The method involves the addition of a known amount (1 microgram) of 62Ni to the sample, the formation of the chelate and the determination by selected-ion monitoring of the m/z 571/574 ratio, which corresponds to 59Co/62Ni. No appreciable memory effect was observed, and an acceptable dynamic range of 100 was found. There was good agreement between the cobalt concentration values determined by gas chromatography-mass spectrometry and electrothermal atomic absorption spectrometry. The present method has high sensitivity and can be used for the quantitation of cobalt at concentrations as low as 1 microgram/l. The use of enriched 62Ni circumvents the problem caused by endogenous nickel and simultaneously provides data on the nickel concentration in the biological sample without any additional experimental effort.

Chelating Agents↗
PubMed1992

Determination of selenium in urine by isotope dilution gas chromatography-mass spectrometry using 4-nitro-o-phenylenediamine, 3,5-dibromo-o-phenylenediamine, and 4-trifluoromethyl-o-phenylenediamine as derivatizing reagents.

An isotope dilution gas chromatography-mass spectrometry method for selenium determination in urine using 76Se as an internal standard is described. Three different derivatizing reagents, 4-nitro-o-phenylenediamine (NPD), 3,5-dibromo-o-phenylenediamine (DBPD), and 4-trifluoromethyl-o-phenylenediamine (TFMPD) were investigated for their gas chromatographic behavior including memory and precision and accuracy of isotope ratio measurements. By these criteria, the performance of these reagents was TFMPD greater than DBPD greater than NPD. Overall precision values of 1 to 7% were observed in determining Se isotope ratios at the 10-ng level, with no significant difference in using any of the three reagents. Memory effect was observed in the order NPD greater than DBPD greater than TFMPD with TFMPD showing no measurable memory effect. Accuracy of the GC-MS method was verified by quantitation of selenium in the NIST freeze-dried urine reference material SRM 2670.

Gas Chromatography-Mass Spectrometry↗
PubMed1992

Synthesis of 3 alpha,6 beta,7 alpha,12 beta- and 3 alpha,6 beta,7 beta,12 beta-tetrahydroxy-5 beta-cholanoic acids.

Chemical synthesis of 3 alpha,6 beta,7 alpha,12 beta- and 3 alpha,6 beta,7 beta,12 beta-tetrahydroxy-5 beta-cholan-24-oic acids is described. 3 alpha,12 beta-Dihydroxy-5 beta-chol-6-en-24-oic acid used as the starting material in the synthesis was prepared via oxidation of 3 alpha,12 alpha-dihydroxy-5 beta-chol-6-en-24-oic acid 3-hemisuccinate at C-12 followed by reduction with potassium/tertiary amyl alcohol. alpha-Epoxidation of the ester diacetate of 3 alpha,12 beta-dihydroxy-5 beta-chol-6-en-24-oic acid with m-chloroperbenzoic acid followed by cleavage of the epoxide with acetic acid and alkaline hydrolysis yielded 3 alpha,6 beta,7 alpha,12 beta-tetrahydroxy-5 beta-cholan-24-oic acid (overall yield 25%). N-Methylmorpholine-N-oxide-catalyzed osmium tetroxide oxidation of the ester diacetate of 3 alpha,12 beta-dihydroxy-5 beta-chol-6-en-24-oic acid followed by alkaline hydrolysis yielded 3 alpha,6 beta,7 beta,12 beta-tetrahydroxy-5 beta-cholan-24-oic acid (overall yield 33%). The structures of the synthesized bile acids were confirmed from their proto nuclear magnetic resonance and mass spectral fragmentation patterns.

Cholic Acids↗
PubMed1992

Effect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex.

Nitric oxide (NO) is an important messenger both systemically and in the CNS. In digital Ca2+ imaging and patch-clamp experiments, clinically available nitroso compounds that generate NO are shown to inhibit responses mediated by the NMDA subtype of the glutamate receptor on rat cortical neurons in vitro. A mechanism of action for this effect was investigated by using the specific NO-generating agent S-nitrosocysteine. We propose that free sulfhydryl groups on the NMDA receptor-channel complex react to form one or more S-nitrosothiols in the presence of NO. If vicinal thiol groups react in this manner, they can form a disulfide bond(s), which is thought to constitute the redox modulatory site of the receptor, resulting in a relatively persistent blockade of NMDA responses. These reactions with NO can afford protection from NMDA receptor-mediated neurotoxicity. Our results demonstrate a new pathway for NO regulation of physiological function that is not via cGMP, but instead involves reactions with membrane-bound thiol groups on the NMDA receptor-channel complex.

Alkylating Agents↗
PubMed1992

Murine macrophage activation after cisplatin or carboplatin treatment.

Murine peritoneal macrophages when treated in vitro with cisplatin (9 micrograms/ml) or carboplatin (50 micrograms/ml) for 2 h are stimulated to form cytoplasmic extensions seeking out tumor cells and establishing cytoplasmic connections; however, no contact is observed with normal cells (fibroblasts and hepatocytes). In addition, cisplatin and carboplatin treatment leads to an increase in the number of lysosomes and their transfer to the tumor cells resulting in lysis (as studied by confocal microscopy). Although calcium seems to be involved in the signalling of macrophage activation, cytosolic calcium does not seem to influence this activation.

Animals↗
PubMed1992

Capillary gas-liquid chromatographic separation of bile alcohols.

Gas-liquid chromatographic separation of C23, C24, C25, C26, and C27 bile alcohols with either 3 alpha, 7 alpha-dihydroxylated or 3 alpha, 7 alpha, 12 alpha-trihydroxylated ring system on two capillary columns, CP-Sil-19 CB and CP-Sil-5 CB, is described. Bile alcohols with two ring hydroxyl groups at 3 alpha- and 7 alpha-positions consistently showed larger retention times on CP-Sil-19 CB columns and smaller retention times on CP-Sil-5 CB columns than the corresponding bile alcohols with three ring hydroxyl groups at 3 alpha-, 7 alpha-, and 12 alpha-positions. Resolutions of all bile alcohols were better on CP-Sil-19 CB columns; however, we hope that the gas-liquid chromatographic characteristics on the two columns will be useful for better identification of bile alcohols in biological fluids.

Cholestanols↗
PubMed1992

Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity.

Excessive activation of NMDA receptors is thought to mediate the calcium-dependent neurotoxicity associated with hypoxic-ischemic brain injury, trauma, epilepsy, and several neurodegenerative diseases. For this reason, various NMDA antagonists have been investigated for their therapeutic potential in these diseases, but heretofore none have proven to be both effective and safe. In the present study, memantine, an adamantane derivative similar to the antiviral drug amantadine, is shown to block the channels activated by NMDA receptor stimulation. From whole-cell and single-channel recording experiments, the mechanism of action of memantine is deduced to be open-channel block, similar to MK-801; however, unlike MK-801, memantine is well tolerated clinically. Compared to MK-801, memantine's safety may be related to its faster kinetics of action with rapid blocking and unblocking rates at low micromolar concentrations. Furthermore, at these levels memantine is an uncompetitive antagonist and should theoretically allow near-normal physiological NMDA activity throughout the brain even in the face of pathologically high focal concentrations of glutamate. These pharmacological properties confer upon memantine a therapeutic advantage against NMDA receptor-mediated neurotoxicity with few side effects compared with other organic NMDA open-channel blockers. Moreover, memantine is increasingly effective against escalating levels of glutamate, such as those observed during a stroke. Low micromolar concentrations of memantine, levels known to be tolerated by patients receiving the drug for the treatment of Parkinson's disease, prevent NMDA receptor-mediated neurotoxicity in cultures of rat cortical and retinal ganglion cell neurons; memantine also appears to be both safe and effective in a rat stroke model. These results suggest that memantine has considerable therapeutic potential for the myriad of clinical entities associated with NMDA receptor-mediated neurotoxicity.

Animals↗
PubMed1991

Determination of copper in urine and serum by gas chromatography-mass spectrometry.

A stable isotope dilution gas chromatography-mass spectrometry method using enriched 65Cu as an internal standard is described for the determination of Cu in urine and serum. Chelating agents N,N'-ethylenebis-(trifluoroacetylacetoneimine) [H2(enTFA2)] and lithium bis(trifluoroethyl)dithiocarbamate [Li(FDEDTC)] were used and evaluated for memory effect. H2(enTFA2) did not show any appreciable memory effect, whereas Li(FDEDTC) was found to have a strong memory effect. Overall precision of 1.6% was obtained for determining Cu isotope ratios at a 10-ng level using H2(enTFA2). Cu concentrations in the National Institute of Standards and Technology (NIST) reference materials, freeze-dried urine SRM 2670, and human serum SRM 909 determined using the H2(enTFA2) chelating agent were in good agreement with the NIST-certified values. Isotope ratios determined by gas chromatography-mass spectrometry on samples with altered isotopic composition were in good agreement with the inductively coupled plasma-mass spectrometry data.

Chelating Agents↗
PubMed1991

A study on existing knowledge about AIDS among Naval personnel.

In the present study 1123 Naval personnel posted in one of the Naval bases were interviewed to find out the existing level of knowledge regarding AIDS and its prevention. The personnel had reasonably fair idea about the disease, modes of transmission and its prevention. It was interesting to observe that personnel had information about heterosexual transmission of disease and it is relevant in our context as in India and other Asian countries, the main transmission is through heterosexual route. About 19.31% of sailors as compared to 2.44% of officers had misconception that the disease is curable. The role of refresher health education efforts for imparting factual up-to-date information to the Naval community has been brought out.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Alanine-based oral rehydration solution: assessment of efficacy in acute noncholera diarrhea among children.

This randomized, double-blind trial determined whether adding 90 mmol/L of alanine with a reduction in glucose to 90 mmol/L (alanine ORS) improves the efficacy of the standard oral rehydration solution (WHO-ORS). One hundred twenty-nine males aged 3-48 months with weight for length greater than or equal to 70% of NCHS, diarrheal duration less than or equal to 96 h, and clinical signs of mild to moderate dehydration were randomly allocated to either treatment group. During 0-6 h of treatment, ORS was offered at 120 ml/kg for rehydration without food or water. Beyond 6 h, ORS was offered as a volume-to-volume replacement for stool losses and a mixed diet of uniform composition was offered in amounts standardized for body weight. The most frequently isolated pathogens in alanine ORS and WHO-ORS groups were rotavirus (42 and 48%, respectively) and enterotoxigenic Escherichia coli (15 and 12%, respectively). In the 0-6 h period when food was withheld, median urine output in ml/kg (8;5, p less than 0.05) and percentage decrease in total serum solids (9:7%, p = 0.06) was significantly greater in alanine ORS than in WHO-ORS; median ORS intake and stool output were marginally lower in the alanine group but the differences were statistically not significant. Between 0 h and recovery, although the median values for duration of diarrhea (56.5 and 65.0 h), ORS consumption (260 and 323 ml/kg), and stool output (188.4 and 216.3 g/kg) were lower in the alanine ORS group, these differences with the WHO-ORS group were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Dot immunobinding assay versus sandwich ELISA in diagnosis of invasive amoebiasis.

Sera from 34 patients of amoebic liver abscess (ALA) and 11 patients with amoebic dysentery (AD) were examined for the presence of specific Entamoeba histolytica (EH) antibodies and amoebic antigen by enzyme linked immunosorbent assay (ELISA) and dot immunobinding assay (DIB). Both techniques were found to be equally sensitive for detecting antiamoebic antibodies (89.5 and 91.9% respectively) and highly specific (100%) in patients of ALA. ELISA was found to be more sensitive (94.4%) in detecting circulating amoebic antigen compared to DIB (68%) in patients of ALA. Specific antibodies, in significant levels, were detected in 3 and 5 patients of AD by ELISA and DIB assay, respectively. As DIB assay is easier to perform and less expensive, is recommended for detection of antibodies in patients with invasive amoebiasis.

Animals↗
PubMed1991

Selective reduction of oxo bile acids: synthesis of 3 beta-, 7 beta-, and 12 beta-hydroxy bile acids.

Preparation of some biologically important keto bile acids is described. Advantage is taken of the preferential ketalization of 3-oxo group in bile acids over 7- and 12-oxo groups for the selective reduction of these keto groups. The method was found to be specially useful for preparation of 7 beta-, 12 alpha, and 12 beta-[3H]-3-oxo bile acids. Improved methods are also described for the preparation of epimers of naturally occurring bile acids at C-3, C-7, and C-12. 3 beta-Hydroxy bile acids (iso-bile acids) were prepared with the use of diethylazodicarboxylate/triphenylphosphine/formic acid. Iso-bile acids were obtained in excellent yields (80-95%) except during synthesis of isoursodeoxycholic acid (yield, 50%). Isoursodeoxycholic acid was, however, prepared in very good yield via epimerization of 3 alpha-hydroxyl group in 7-oxolithocholic acid followed by stereoselective reduction of 7-oxo group. A highly efficient method for the reduction of 7-oxo and 12-oxo groups was developed. Thus, 7-oxolithocholic acid and 7-oxoisolithocholic acid on reduction with potassium/tertiary amyl alcohol yielded ursodeoxycholic acid and isoursodeoxycholic acid in yields of 96% and 94%, respectively, while reduction of 7-oxodeoxycholic acid resulted in ursocholic acid in 93% yield. In a similar manner, reduction of 12-oxolithocholic acid and 12-oxochenodeoxycholic acid yielded 3 alpha, 12 beta-dihydroxy-5 beta-cholanoic acid (lagodeoxycholic acid; 92% yield) and 3 alpha, 7 alpha, 12 beta-trihydroxy-5 beta-cholanoic acid (lagocholic acid, 86% yield).

Bile Acids and Salts↗
PubMed1990

Determination of chromium in urine by stable isotope dilution gas chromatography/mass spectrometry using lithium bis(trifluoroethyl)dithiocarbamate as a chelating agent.

An isotope dilution gas chromatography/mass spectrometry method using lithium bis(trifluoroethyl)dithiocarbamate as a chelating agent is described for the determination of chromium in urine. A wet digestion procedure with HNO3-H2O2 is used for oxidizing the organic matter associated with urine samples. The isotope ratios are measured by selected ion monitoring in a general-purpose mass spectrometer using a 10-m fused silica capillary column. Memory effect, in sequential analyses of samples with different isotope ratios, was evaluated by preparing a series of synthetic mixtures and was found to be negligible. The accuracy of the method was verified by quantitation of chromium in the NIST freeze-dried urine reference material, SRM-2670, with a recommended chromium concentration of 13 micrograms/L in the normal level and certified chromium concentration of 85 +/- 6 micrograms/L in the elevated level.

Chelating Agents↗
PubMed1990

Synthesis and biological evaluation of prodrugs of zidovudine.

A series of prodrugs of zidovudine (AZT) has been synthesized in an effort to enhance the uptake of the prodrugs by the HIV-1 infected cells and to increase the plasma half-life of AZT. The 5'-OH function of AZT was esterified with various acids in the presence of DCC and 4-(dimethylamino)pyridine (DMAP). The prodrug moieties included (a) morpholine and N-phenylpiperazine-1-acetic acid, (b) 1,4-dihydro-1-methyl-3-nicotinic acid, (c) retinoic acid, and (d) certain amino acids. The anti-HIV-1 activity of the esters was determined in peripheral blood lymphocytes. The IC50 for AZT in this system was 0.12 microM whereas for prodrugs it ranged from 0.05 to 0.2 microM. The prodrugs were generally less cytotoxic than AZT except the retinoic acid ester. In vitro hydrolysis of the various esters in human plasma indicated that these agents were relatively stable toward plasma esterases with t1/2 ranging from 10 to 240 min. Drug uptake studies in H9 cells with radiolabeled analogues demonstrated that the retinoic acid ester achieved approximately 4-fold higher intracellular concentration than [3H]AZT. However, 1,4-dihydro-1-methyl-3-[(pyridylcarbonyl)oxy] ester (5) was the most active agent of this series and had a higher therapeutic index than AZT.

Animals↗
PubMed1990

Glycine, glycyl-glycine and maltodextrin based oral rehydration solution. Assessment of efficacy and safety in comparison to standard ORS.

We evaluated the efficacy and safety of an oral rehydration solution containing glycyl-glycine, glycine, and maltodextrin (GGG-ORS), in comparison to the glucose based ORS (standard ORS). The osmolality of the GGG-ORS (305 mOsm/l) and standard ORS (311 mOsm/l) was similar. Ninety-two children presenting with acute gastroenteritis and moderate dehydration, aged 3 months to 3 years, were randomly assigned to receive standard ORS or GGG-ORS. All the patients were successfully rehydrated orally. The two groups were comparable for baseline characteristics including the microbial etiology. Rotavirus (49%, 36%), ETEC (11%, 18%) or a combination of rotavirus and ETEC (15%, 9%) were the main stool pathogens isolated. There was no significant difference in the mean stool output or duration of diarrhoea between the two groups. Patients in the GGG-ORS group had higher urine output (p less than 0.01) and weight gain (p less than 0.05) in the initial 6 hours when feeding was withheld, but no such differences were observed beyond this period. Hypernatremia did not develop in any patient during the study. We conclude that glycine and glycyl-glycine supplemented oral rehydration solution does not have any therapeutic advantage in the treatment of acute gastroenteritis with moderate dehydration caused predominantly by rotavirus.

Acute Disease↗
PubMed1990

Immunocytochemical demonstration of vasopressin binding in rat kidney.

We investigated the immunoperoxidase demonstration of vasopressin (VSP) bound to paraffin-embedded sections of rat kidney and the effects of various fixatives. Slices of rat kidney from normal and 4-day water-deprived rats were incubated with 10(-7) M VSP, fixed, and embedded in paraffin. Hydrated sections of these tissues were again incubated with 10(-7) M VSP or 10(-7) M VSP and 10(-5) M oxytocin (OXY). VSP bound to the sections was demonstrated using rabbit anti-Arg8 VSP antiserum and peroxidase-labeled second antibody. In sections of kidney from both normal and water-deprived rats, immunoperoxidase labeling was most intense in the renal papilla and was restricted to the cells of the ducts of Bellini and loops of Henle. In the medulla, the collecting ducts and medullary thick ascending limbs of Henle were moderately stained. In the normal kidney sections there was no staining of the proximal tubules, distal convoluted tubules (DCT), and only slight staining of the cortical collecting ducts (CCD). However, in the water-deprived rats there was a considerable increase in the staining of the DCT and CCD. Simultaneous incubation in OXY and VSP resulted in reduced immunoperoxidase labeling of the tubules. Omission of VSP incubation led to a similar decrease in stain intensity, indicating a specificity for the sites of VSP binding. This technique allows the identification of cells responsible for the binding of VSP in the kidney.

Animals↗
PubMed1989

Drug eruptions (a series of 148 cases).

A total number of 148 patients, comprising of 101 males and 47 females diagnosed as drug eruptions were reviewed. The youngest patient was eight and the oldest 73 years. The mean age was 34 years. 75(50.7%) patients were in the age group of 20 to 40 years. In 88(59.5%) pruritus was the chief associated symptom. 116(78.4%) developed eruptions within 2 weeks. 29(19.6%) had single site involvement, 92(62.2%) had lesions at more than one site and 25(16.9%) patients had generalised skin and mucous membrane involvement. The commonest skin reactions were fixed drug eruptions in 39(26.4%) cases. Almost all types of drug eruptions were observed. The eruptions were caused by 37 different drugs, the commonest being sulphonamides in 28(18.9%) cases. Systemic side effects were recorded in 13(8.8%) patients. 76(51.4%) were treated with topical medicaments. Out of the remaining, 33(22.3%) were managed by antihistamines and 26(17.6%) by steroids in addition to topical therapy. No treatment was required in 13(8.8%). 117(79.1%) were treated as out patients and 31(20.9%) were hospitalised. One (0.7%) patient died of toxic epidermal necrolysis due to penicillamine.

Adult↗