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Biomedical subjects

A K Pathak

Publications and source records attributed to A K Pathak.

At least 19 recordsLinked to original sources
PubMed2006

Analgesic activity of Calotropis gigantea flower.

The alcoholic extract of the flowers of Calotropis gigantea was administered orally and explored for its analgesic activity in chemical and thermal models in mice. In acetic acid induced writhing test, an inhibition of 20.97% and 43.0% in the number of writhes was observed at the doses of 250 and 500 mg/kg, respectively. In the hot plate method the paw licking time was delayed. The analgesic effect was observed after 30 min of dose administration which reached its maximum after 90 min.

Acetic Acid↗
PubMed2006

Microhydration shell structure in Cl2*-.nH2O clusters: A theoretical study.

We present the results of a detailed study on structure and electronic properties of hydrated cluster Cl2*-.nH2O (n = 1-7) based on a nonlocal density functional, namely, Becke's [J. Chem. Phys. 98, 1372 (1993)] half and half hybrid exchange-correlation functional with a split valence 6-311++G(d,p) basis function. Geometry optimizations for all the clusters are carried out with various possible initial guess structures without any symmetry restriction. Several minimum energy structures (conformers) are predicted with a small difference in total energy. There is a competition between the binding of solvent H2O units with Cl2*- dimer radical anion directly through ion-molecule interaction and forming interwater hydrogen-bonding network in Cl2*-.nH2O (n > or = 2) hydrated cluster. Structure having interwater H-bonded network is more stable over the structure where H2O units are connected to the solute dimer radical anion Cl2*- rather independently either by single or double H bonding in a particular size (n) of hydrated cluster Cl2*-.nH2O. At the maximum four solvent H2O units reside in interwater H-bonding network present in these hydrated clusters. It is observed that up to six H2O units are independently linked to the anion having four double H bondings and two single H bondings suggesting the primary hydration number of Cl2*- to be 6. In all these clusters, the odd electron is found to be mostly localized over the two Cl atoms and these two atoms are bound by a three-electron hemibond. Calculated interaction (between solute and different water clusters) and vertical detachment energy profiles show saturation at n = 6 in the hydrated cluster Cl2*-.nH2O (n = 1-7). However, calculated solvation energy increases with the increase in number of solvent H2O molecules in the cluster. Interaction energy varies linearly with vertical detachment energy for the hydrated clusters Cl2*-.nH2O (n < or = 6). Calculation of the vibration frequencies show that the formation of Cl2*(-)-water clusters induces significant shifts from the normal stretching modes of isolated water. A clear difference in the pattern of IR spectra is observed in the O-H stretching region of water from hexa- to heptahydrated cluster.

Journal Article↗
PubMed2006

A comparative ab initio study of Br2*- and Br2 water clusters.

The work presents ab initio results on structure and electronic properties of Br2*-.nH2O(n=1-10) and Br2.nH2O(n=1-8) hydrated clusters to study the effects of an excess electron on the microhydration of the halide dimer. A nonlocal density functional, namely, Becke's half-and-half hybrid exchange-correlation functional is found to perform well on the present systems with a split valence 6-31++G(d,p) basis function. Geometry optimizations for all the clusters are carried out with several initial guess structures and without imposing any symmetry restriction. Br2*-.nH2O clusters prefer to have symmetrical double hydrogen-bonding structures. Results on Br2.nH2O(n>or=2) cluster show that the O atom of one H2O is oriented towards one Br atom and the H atom of another H2O is directed to other Br atom making Br2 to exist as Br+-Br- entity in the cluster. The binding and solvation energies are calculated for the Br2*-.nH2O and Br2.nH2O clusters. Calculations of the vibrational frequencies show that the formation of Br2*- and Br2 water clusters induces significant shifts from the normal modes of isolated water. Excited-state calculations are carried out on Br2*-.nH2O clusters following configuration interaction with single electron excitation procedure and UV-VIS absorption profiles are simulated. There is an excellent agreement between the present theoretical UV-VIS spectra of Br2*-.10H2O cluster and the reported transient optical spectra for Br2*- in aqueous solution.

Journal Article↗
PubMed2006

Quality of life in newly diagnosed patients with lung cancer in a developing country: is it important?

There are no data regarding quality of life (QoL) assessments in lung cancer in developing countries like India. Quality of life was evaluated in 76 newly diagnosed lung cancer patients by using the World Health Organization Quality of Life questionnaire in Hindi (WHOQoL-Bref) (men 87%). The mean age was 55 years (SD = 10). Cough, dyspnoea, chest pain and haemoptysis were present in 83%, 72%, 66% and 43% of patients respectively. The median duration of symptoms was 5.9 months (range 1-13). Eighty-nine per cent had non-small cell lung cancer. The median pack-years smoked was 23 (range 0.5-88). Most patients (53%) had a Karnofsky's Performance Status (KPS) of 70 and 83% had stage III or IV disease. Quality of life did not correlate with age, gender, presence or duration of symptoms, histological type, stage of disease or degree of smoking. The physical and psychological domains of QoL correlated significantly with the KPS (P = 0.001 and P = 0.01 respectively). Patients with a KPS of 80 had better physical (P < 0.001), psychological (P < 0.01) and social (P < 0.05) QoL than those with a KPS of 70. In conclusion, patients with lung cancer in a developing country like India have an unsatisfactory QoL. The Karnofsky's Performance Scale is a simple and reliable surrogate marker for assessing QoL in these patients. Larger multi-centric studies may help in providing a more comprehensive evaluation of the effect of various demographic and clinical variables on QoL in this setting.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Studies on (beta,1-->5) and (beta,1-->6) linked octyl Gal(f) disaccharides as substrates for mycobacterial galactosyltransferase activity.

The emergence of multi-drug resistant (MDR) strains of Mycobacterium tuberculosis (MTB) and the continuing pandemic of tuberculosis emphasizes the urgent need for the development of new anti-tubercular agents with novel drug targets. The recent structural elucidation of the mycobacterial cell wall highlights a large variety of structurally unique components that may be a basis for new drug development. This publication describes the synthesis, characterization, and screening of several octyl Galf(beta,1-->5)Galf and octyl Galf(beta,1-->6)Galf derivatives. A cell-free assay system has been utilized for galactosyltransferase activity using UDP[14C]Galf as the glycosyl donor, and in vitro inhibitory activity has been determined in a colorimetric broth microdilution assay system against MTB H37Ra and three clinical isolates of Mycobacterium avium complex (MAC). Certain derivatives showed moderate activities against MTB and MAC. The biological evaluation of these disaccharides suggests that more hydrophobic analogues with a blocked reducing end showed better activity as compared to totally deprotected disaccharides that more closely resemble the natural substrates in cell wall biosynthesis.

Antitubercular Agents↗
PubMed2001

Studies on alpha(1-->5) linked octyl arabinofuranosyl disaccharides for mycobacterial arabinosyl transferase activity.

The appearance multi-drug resistant Mycobacterium tuberculosis (MTB) throughout the world has prompted a search for new, safer and more active agents against tuberculosis. Based on studies of the biosynthesis of mycobacterial cell wall polysaccharides, octyl 5-O-(alpha-D-arabinofuranosyl)-alpha-D-arabinofuranoside analogues were synthesized and evaluated as inhibitors for M. tuberculosis and Mycobacterium avium. A cell free assay system has been used for the evaluation of these disaccharides as substrates for mycobacterial arabinosyltransferase activity.

Antitubercular Agents↗
PubMed2001

Altered immunomodulating and toxicological properties of degraded Quillaja saponaria Molina saponins.

Quillaja saponins are readily hydrolyzed under physiological conditions, yielding deacylated forms that are significantly less toxic than their precursors. Yet, deacylated saponins are unable to stimulate a strong primary immune response. Although deacylated saponins elicit a strong total IgG response, their capacity to stimulate a Thl type IgG isotype profile (i.e. high levels of IgG2a and IgG2b) has been significantly diminished. Instead, an IgG profile closer to that of a Th2 immune response is stimulated (i.e. high IgG1 levels). Deacylated saponins have also lost their capacity to elicit an effective T cell immunity, as shown by their stimulation of a marginal lymphoproliferative response and their inability to elicit the production of cytotoxic lymphocytes (CTL). Modification of the immune-modulating properties brought by the degradation of quillaja saponins during vaccine storage may change the intended immune response from a Th1 to a Th2 type. This alteration would have negligible effects on vaccines depending on Th2 immunity mediated by neutralizing antibodies. However, the performance of vaccines directed against intracellular pathogens as well as therapeutic cancer vaccines may be seriously affected by the loss of their capacity to stimulate both a Th1 immune response and the production of CTL.

Adjuvants, Immunologic↗
PubMed2001

Carcinoma of the gallbladder: a retrospective review of 99 cases.

Since the first description of the carcinoma of the gallbladder, about two centuries ago, this disease has evaded all attempts at early detection and a potential cure. There are only a few studies involving the Indian population, which has a high incidence of gallbladder cancer. Indians are ethnically and culturally different from their Western counterparts, for whom the incidence of this disease is comparatively low. The present study was conducted prospectively on 99 consecutive cases of carcinoma of the gallbladder of 736 patients with biliary diseases admitted to one surgical unit at the University Hospital. The staging, histological type, and grade were correlated with the clinical outcome. Abdominal pain (82.8%) and abdominal mass (73.7%) were the main presenting features. The diagnosis was obtained by ultrasonography (USG) in 93 of 99 cases and confirmed by fine-needle aspiration cytology (FNAC) in 70 patients. Ultrasonography, however, was found to be inadequate for accurate staging of the disease. Based on the TNM classification, 3 (3.0%), 12 (12.1%), 14 (14.1%), 12 (12.1%), and 58 (58.6%) patients had stage 0, I, II, III, and IV disease, with a corresponding mean survival of 28.3, 13.8, 7.5, 5.2, and 3.7 months, respectively. Carcinoma of the gallbladder is difficult to diagnose early due to its vague symptomatology. A high index of suspicion and health education seem to be the only answers available for early detection and improvement of survival.

Adenocarcinoma↗
PubMed2000

Development of semisynthetic triterpenoid saponin derivatives with immune stimulating activity.

Aldehyde-containing triterpene saponins have adjuvant properties, but only those from Quillaja saponaria Molina stimulate the production of cytotoxic T lymphocytes (CTL) against exogenous antigens. Quillaja saponins have two normonoterpene ester moieties, linked linearly to their fucosyl residue, that play a critical role in the stimulation of CTL. These ester moieties are also responsible for these saponins' instability and toxicity. Based on the structure-activity relationships for the different groups of Q. saponaria saponins, new semi-synthetic analogs were developed that have the adjuvanticity of quillaja saponins, yet with less toxicity and greater stability in aqueous solutions. The quillaja saponin analogs were prepared by replacing their hydrolytically unstable ester groups with another lipophilic chain linked by a stable amide bond on these saponins' glucuronic acid residue. One of these analogs, GPI-0100, is a dodecylamide saponin derivative that stimulates an antibody isotype profile that corresponds to a Th1 type immune response, as well as CTL production against exogenous antigens.

Adjuvants, Immunologic↗
PubMed2000

Possible involvement of cholinergic and adrenergic mechanisms in changing contractility of guinea pig ileum by Ipomoea carnea.

The study aimed to elucidate the mechanism (s) of action of Ipomoea carnea leaf juice (ILJ) in changing contractility of guinea pig ileum. ILJ produced dose-dependent (10-10000 microg/ml) triphasic responses. The initial contractile phase was blocked by atropine (1 microg/ml) but had additive effect with acetylcholine (2 ng/ml) or carbachol (2 ng/ml). Neostigmine (30 ng/ml) or lignocaine (50 microg/ml) failed to alter the response. In cold-induced denervated preparations, this phase was augmented. The relaxatory phase of ILJ was not modified by phenoxybenzamine (35 microg/ml) but was reduced by propranolol (1 microg/ml) and abolished by lignocaine (50 microg/ml). The final contractile phase of ILJ was not affected by atropine (1 microg/ml). These results suggest that the triphasic response of ILJ is possibly mediated through cholinergic, adrenergic and non-cholinergic mechanisms, respectively.

Adrenergic Agents↗
PubMed1999

Studies on beta-D-Gal(f)-(1-->4)-alpha-L-Rha(p) octyl analogues as substrates for mycobacterial galactosyl transferase activity.

The biochemically unique structures of sugar residues in the outer cell wall of Mycobacterium tuberculosis (MTB) make the pathways for their biosynthesis and utilization attractive targets for the development of new and selective anti-tubercular agents. A cell-free assay system for galactosyltransferase activity using UDP[14C]Gal as the glycosyl donor, as well as an in vitro colorimetric broth micro-dilution assay system, were used to determine the activities of three beta-D-gal(f)(1-->4)-alpha-L-rham(p) octyl disaccharides as substrates and antimycobacterial agents respectively. The cell-free enzymatic studies using compounds 8 and 10 suggested that these disaccharides bind to and are effective substrates for a putative mycobacterial galactosyltransferase. The modified acceptor 8 was found to be a slower but prolonged binder as compared to the less substituted analogue 10 as evidenced by their Km and Vmax values. Moderate antimycobacterial activity was observed with compounds 8 and 9 against MTB H37Ra and three clinical isolates of Mycobacterium avium complex (MAC).

Anti-Bacterial Agents↗