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Biomedical subjects

R Singh

Publications and source records attributed to R Singh.

At least 343 records · Page 19Linked to original sources
PubMed1997

Development and characterization of a mini capsular extrusion system for enteric delivery of metronidazole bearing liposomes.

A capsular extrusion system was developed for enteric delivery of metronidazole loaded liposomes. The system is essentially based on a miniosmotic pump except that the extrusion in the present system is brought about by the swelling of a swellable polymer which raises the vestibule and extrudes out the contents through a deliver orifice. Drug reservoir of the system contained freeze dried liposomes which become hydrated prior to extrusion. Extruded liposomes were uniform in size with 45-68% incorporation of metronidazole. When tested for in vitro antiamoebic and antibacterial activity it was found that the effectiveness of liposomal metronidazole was significantly higher as compared to the unformulated drug.

Amebicides↗
PubMed1997

Antifilarial activity of Mallotus philippensis Lam. on Setaria cervie (Nematoda: Filarioidea) in vitro.

The effect of aqueous and alcoholic extracts of the leaves of Mallotus philippensis (Lam.) Muell. Arg. was studied on the spontaneous movements of the whole worm and nerve-muscle (n.m.) preparation of Setaria cervi and on the survival of microfilariae in vitro. Both the extracts caused inhibition of spontaneous motility of whole worm and the n.m. preparation of S. Cervi characterized by initial stimulation followed by depression in amplitude. The tone and rate of contractions remained visibly unaffected. Aqueous extract at higher concentration showed immediate reduction in tone. The concentration required to inhibit the movements of n.m. preparation was 1/5th for aqueous and 1/11th for alcoholic extract compared to that for the whole worm, suggesting a cuticular permeability barrier. The stimulatory response of acetylcholine was blocked by aqueous extract on whole worm movements. On the microfilariae the LC50 and LC90 were 18 and 20 ng/ml for aqueous and 12 and 15 ng/ml for alcoholic extracts respectively.

Animals↗
PubMed1997

Potential antifilarial activity of roots of Asparagus adscendens Roxb, against Setaria cervi in vitro.

Effect of aqueous and alcoholic extracts of the roots of A. adscendens was studied on the spontaneous movements of whole worm and nerve muscle (n.m.) preparation of S. cervi and on the survival of microfilariae in vitro. Aqueous as well alcoholic extracts caused inhibition of spontaneous motility of whole worm and n.m. preparation of S. cervi characterized by initial, short lasting small increase in amplitude and tone of contractions followed by paralysis. The initial stimulatory effect was not observed by aqueous extract on n.m. preparation. The concentration required to inhibit the movements of n.m. preparation was 1/4th for aqueous and 1/3rd for alcoholic extract suggesting a cuticular permeability barrier. The effect of acetylcholine on n.m. preparation was concentration related being more with a concentration of 5 micrograms/ml as compared to 1 microgram/ml. Both alcoholic as well as aqueous extracts caused death of microfilariae in vitro, LC50 and LC90 being 8 and 16 ng/ml for aqueous, 3 and 12 ng/ml for alcoholic extracts respectively.

Animals↗
PubMed1997

The effects of macrolide and quinolone antibiotics in methicillin-resistant Staphylococcus aureus biofilm growth.

Recent studies demonstrate that 14-membered macrolides increase permeability and destruction of Pseudomonas biofilms. The effect of a macrolide antibiotic, erythromycin, on methicillin-resistant Staphylococcus aureus (MRSA) biofilm on Silastic catheter materials in comparison with two different quinolone antibiotics, sparfloxacin (SPFX) and a new quinolone, SYN 1193, was examined. Two different MRSA strains were grown in biofilm, using Mueller-Hinton broth with and without the addition of 10% pooled normal human serum (PNHS), in a modified Robbins device, at 37 degrees C for 24, 48, and 72 hours. Two different clinical MRSA strains were used and minimum bactericidal concentration (MBC) were determined at the time intervals mentioned. Three different dosages of each antibiotic were tested: 5.0, 20.0, and 50.0 micrograms/mL. In addition, a constant dosage of SPFX and SYN 1193, in combination with varying dosages of erythromycin, was tested under similar experimental conditions. SYN 1193 demonstrated the highest MBC in comparison to SPFX; addition of PNHS did not alter the effect of SYN 1193. However, erythromycin alone and in combination with SPFX and SYN 1193 had no effect on MBC. We conclude that (1) macrolide antibiotic erythromycin has poor MRSA biofilm permeability and killing in comparison to SPFX and SYN 1193, and (2) SYN 1193 had the highest MBC to MRSA biofilm.

Anti-Bacterial Agents↗
PubMed1997

Enzymes of glycolytic and pentose phosphate pathways in cytosolic and leucoplastic fractions of developing seeds of Brassica campestris.

Distribution of the enzymes of glycolytic and pentose phosphate pathways were studied in cytosolic and leucoplastic fractions of the developing seeds of Brassica. Leucoplasts were isolated using a discontinuous percoll gradient. Intactness of leucoplasts was checked by ADP-glucose pyrophosphorylase assay in presence and absence of triton X-100. No contamination by microbodies, mitochondria and cytosol was observed as assessed by measuring the activities of marker enzymes. The recovery, latency and specific activity of each enzyme in different fractions were compared. The leucoplastic fraction contained complete set of the enzymes of glycolytic and pentose phosphate pathways, indicating that the two subcellular compartments metabolize carbon independently by these pathways. However, the enzymes showed higher activities in cytosolic fraction as compared to those in the leucoplasts, suggesting the need for exchange of metabolites in the two compartments through various translocators, for acting in cooperation to produce energy, reducing power and carbon skeletons for different biosynthetic activities in the non-photosynthetic plastids. Based on these compartmentation studies, a model for carbon flow for fatty acid synthesis in leucoplasts of developing Brassica seeds has been proposed.

Acetates↗
PubMed1997

Purification and characterization of neutral invertase from chickpea nodules.

Neutral invertase from nodules of chickpea (Cicer arietinum L.) was isolated and purified by ammonium sulphate fractionation, gel filtration and DEAE-cellulose column chromatography. The purified enzyme was stable between 0 to 40 degrees C beyond which it was irreversibly denatured. Optimum temperature and pH of the enzyme were 37 degrees C and 7.0, respectively. K(m) for sucrose was 14.2 mM and Vmax was 4.8 mumole hr-1. The enzyme was inhibited by several metal ions. From the temperature effect on K(m) and Vmax values, the energy of activation (Ea), enthalpy change (delta H) and entropy change (delta S) of the enzyme were calculated to be 147 kJmol-1, -4.10 kJmol-1 and -2.33 JK-1mol-1, respectively. By employing photo-oxidation and chemical modification and by studying the effect of pH on K(m) and Vmax, the involvement of sulphydryl-, imidazole- and alpha-amino groups in the active site of the enzyme has been indicated.

Binding Sites↗
PubMed1996

Interaction of U2AF65 RS region with pre-mRNA branch point and promotion of base pairing with U2 snRNA [corrected].

The mammalian splicing factor U2AF65 binds to the polypyrimidine tract adjacent to the 3' splice site and promotes assembly of U2 small nuclear ribonucleoprotein on the upstream branch point, an interaction that involves base pairing with U2 small nuclear RNA (snRNA). U2AF65 contains an RNA binding domain, required for interaction with the polypyrimidine tract, and an arginine-serine-rich (RS) region, required for U2 snRNP recruitment and splicing. Here it is reported that binding of U2AF65 to the polypyrimidine tract directed the RS domain to contact the branch point and promoted U2 snRNA-branch point base pairing even in the absence of other splicing factors. Analysis of RS domain mutants indicated that the ability of U2AF65 to contact the branch point, to promote the U2 snRNA-branch point interaction, and to support splicing are related activities, requiring only a few basic amino acids. Thus, the U2AF65 RS domain plays a direct role in modulating spliceosomal RNA-RNA interactions.

Amino Acid Sequence↗
PubMed1996

[Cushing's disease: successful surgery through improved preoperative tumor localization].

OBJECTIVE: To study the effect of improved preoperative tumour localisation on the outcome of transsphenoidal surgery for Cushing's disease. DESIGN: Retrospective. SETTING: University Hospital Rotterdam, the Netherlands. METHODS: The case records were studied of 61 patients, operated on for Cushing's disease due to a corticotrophin-secreting microadenoma (diameter < 10 mm), in the period January 1985-September 1995. From 1985, preoperative tumour localisation was performed with computed tomography (CT), from 1989 with Magnetic Resonance Imaging (MRI) and Bilateral Simultaneous Inferior Petrosal Sinus Sampling (BSIPSS). The definition of a successful operation was: morning serum cortisol < 500 nmol/l, and of cure: morning serum cortisol < 140 nmol/l or 24-hr cortisoluria < 250 nmol. RESULTS: In 1985-1988, a microadenoma was localised preoperatively in 8/22 patients (36%), the operation was successful in 12 (55%), of which 4 (18%) were cured. In 1989-1991, a microadenoma was localised in 12/15 patients (80%), the operation was successful in 11 (73%), of which 4 (27%) were cured. In 1992-1995 a microadenoma was localised preoperatively in 23/24 patients (96%), the operation was successful in 19 (79%), of which 17 (71%) were cured. In the cured group, there was a low incidence (< 10%) of postoperative hypopituitarism in all three periods. There were 1, 0 and 1 recurrences of Cushing's disease respectively after initial cure. CONCLUSION: In our institution, improved preoperative localisation of corticotrophin-secreting hypophyseal microadenomas was associated with an important increase of success and cure rate of transsphenoidal surgery, while there was no increase in postoperative hypopituitarism or recurrences of Cushing's disease.

Adenoma↗
PubMed1996

Formation of N-substituted 2-iminothiolanes when amino groups in proteins and peptides are modified by 2-iminothiolane.

The reagent 2-iminothiolane (2-IT) is used to introduce thiol groups into proteins and peptides by reactions of their amino groups. In this study, we report that the thiol adduct initially formed by the reaction of an amine with 2-IT (a 4-mercaptobutyramidine) is unstable and decays by a first-order process to a nonthiol product (an N-substituted 2-iminothiolane) with the loss of ammonia. The thiol adducts derived from amines of low pKa values (approximately 8; e.g., alpha-amino groups in peptides) decay more rapidly than those derived from amines of high pKa values ( similar 9.5; e.g., benzylamine, ethanolamine, lysine residues in proteins), with half-lives at pH 8 ranging from 0.3 to 3 h at 23 degrees C, and from 1 to 44 h at 0 degrees C. In the case of reactions of peptides with 2-IT, the substituents at the alpha-carbon also influence the decay of the initial thiol adducts. The decay of the initial thiol adduct to an N-substituted 2-iminothiolane was confirmed for the reaction between benzylamine and 2-IT by the isolation of N-benzyl-2-iminothiolane and its characterization by elemental analysis and mass spectrometry. The decay of the initial 4-mercaptobutyramidine is prevented if the thiol group is capped, e. g., in the form of a disulfide group, or if the solution is acidified (pH 3 to 4). Immediate capping of the thiol is, therefore, recommended when using 2-IT in the formation of bioconjugates. For amines of high pKa, the N-substituted 2-iminothiolane product can be cleaved by hydroxylamine, resulting initially in a thiol which then decays to N-hydroxy-2-iminothiolane regenerating the original amine. For amines of low pKa, the N-substituted 2-iminothiolane product can be hydrolyzed at pH 5 to generate a stable thiol with an amide functionality (an N-substituted 4-mercaptobutyramide).

4-Aminobenzoic Acid↗
PubMed1996

Male breast cancer: a retrospective study from a regional cancer center in northern India.

Over a 7-year period from 1987 to 1993, 41 male breast cancer patients were seen in the breast cancer clinic of the Institute Rotary Cancer Hospital (IRCH) at the All India Institute of Medical Sciences (AIIMS). Their mean age was 54.2 years; and duration of symptoms ranged from 1 to 84 months with a mean of 15.1 months. Breast lump was the commonest presenting symptom. Fine needle aspiration cytology (FNAC) was the commonest diagnostic procedure. The TNM stage distribution was stage I, 5; stage II, 13; stage III, 17; and stage IV, 6. Radical mastectomy (25/36) was the commonest surgical procedure. Locoregional radiotherapy was given in 15 patients. Thirty patients received systemic adjuvant therapy (chemotherapy or tamoxifen, or a combination of the two). Local or distant recurrence occurred in 8 patients (8/31, 28.3%). Actuarial overall and disease-free survival was 100% and 80.1% at 2 years and 91.7% and 66.7% at 4 years, respectively. On univariate analysis, axillary lymph node status and age were found to affect disease-free survival significantly. Advanced stage of disease at presentation is common in Indian patients and will continue to influence treatment policies. Neoadjuvant chemotherapy needs to be evaluated for locally advanced tumors to improve outcome. Multicentric studies are necessary to define the relative roles of tamoxifen and chemotherapy for adjuvant treatment.

Adult↗
PubMed1996

In vitro metabolism of a potent HIV-protease inhibitor (141W94) using rat, monkey and human liver S9.

Compound 141W94 (Vertex VX478) (3S)-tetrahydro-3-furyl N-[((S,2R)-3-(4-amino-N-isobutylbenzenesulfonamido)-1-benzyl- 2-hydroxypropyl] carbamate, is a potent HIV-protease inhibitor and is currently undergoing clinical trials. The purpose of this study was the rapid identification of the phase I and II in vitro metabolite of 141W94 using mass spectrometry. Four different sources of liver S9 fractions were used for studying comparative in vitro metabolism of 141W94. They were obtained from Arochlor-induced rat, normal (untreated) rat, cynomolgus monkey and human livers. Selected incubations were supplemented with uridine diphosphate glucuronic acid and the reduced form of glutathione. The predominant species seen in the incubation mixture was the parent compound 141W94. Metabolites arising from ring opening to form the diol and carboxylic acid and oxidation of the tetrahydrofurran ring (formation of dihydrofuran) were identified. In addition, of the two monohydroxylated products identified, one resulted from hydroxylation on the aniline ring and the other from hydroxylation at the benzylic position. Two different glucuronides were also observed. Comparing the three species, very little metabolism was seen in the normal (non-induced) rat. The metabolic profile and extent of metabolism with induced rat, monkey and human S9 was similar. Induced rat S9 incubation showed the formation of two unique metabolites that were not seen in non-induced rat, monkey and human S9 fractions. They were the monohydroxylated glucuronide and a carbamate cleavage product. The metabolites were identified using mass spectrometry based on their molecular masses and fragmentation patterns.

Animals↗
PubMed1996

Theoretical permutation gel electrophoretic analysis of a curved DNA fragment located in circular permutation.

Using the theoretical model for DNA curvature, we analyzed a set of fragments with a curved insert located in circular permutation. The theoretical permutation analysis of each of the cyclically located fragments reveals the presence of a shifting molecular bend locus. The delineation of the molecular bend locus associated with the fragments obtained by a second permutation helps in providing an explanation for the differential mobility behavior of the fragments.

Animals↗
PubMed1996

Acute toxicity of synthetic Gymnodinium breve toxin metabolite and its analogues in mice.

Acute toxicity of synthetic Gymnodinium breve toxin metabolite and its analogues has been investigated in mice. The anticholinesterase potencies of the toxin metabolite and its analogues were determined in vitro as well as in vivo. The intraperitoneal LD50 of the parent metabolite O,O-dipropyl(E)-2-(1-methyl-2-oxopropylidene) phosphorohydrazidothioate(E)oxime in mice was higher compared to LD50 values of its analogues. The in vitro acetylcholinesterase (AChE)-inhibiting potency values were higher for diethoxy(P = O) analogue than for diispropoxy(P = O) analogue. Lethal doses of parent metabolite and its analogues significantly inhibited AChE activity in the blood and brain of mice 1 hr postexposure. The maximum inhibition by the parent metabolite was observed in both tissues. The percentage inhibition of AChE activity was greater in the blood than in the brain. The results indicate that these agents have anticholinesterase action specifically in the blood. In conclusion, the parent toxin metabolite is a more potent inhibitor of AChE in vivo, whereas higher toxicity is associated with other analogues, suggesting the involvement of other factors influencing the toxicity, which needs to be further investigated.

Animals↗
PubMed1996

Subtractive versus Ratio Model of "Fair" Allocation: Can the Group Level Analyses Be Misleading?

Two models of equity judgments are ratio and subtraction. Proponents of the former assume a linear relationship between the subjective feelings of equity and their overt expressions; those of the latter assume a monotonic relationship. Consequently, the ratio and subtractive rules are tested with the raw and monotonically rescaled data, respectively. I evaluated these two approaches with managers and students from India. Experiment 1 varied merit and pay of two persons and obtained judgments of difference between unfairness to them. Experiments 2 and 3 manipulated two inputs of two persons and studied "fair" reward for them. I analyzed both the raw and rescaled data at the group and individual levels. The group analyses supported the ratio model; the individual analyses showed that majority was consistent with the subtractive model. Discrepant results from these analyses were due to individual differences in the models employed and use of the response scale. Implications of the findings are discussed for cross-cultural and developmental research in "fair" allocation.

Journal Article↗