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Showing papers by "Central Drug Research Institute published in 1997"


Journal ArticleDOI
TL;DR: The results indicate that wounding results in loss of different free radical scavengers both enzymatic and non-enzymatic which either partially or completely recover following healing.
Abstract: In the present investigation the involvement of free radicals in a self-healing cutaneous wound has been demonstrated. The levels of different enzymatic and non-enzymatic antioxidants have been studied in 2,4,7 and 14 days old wounds and compared with normal skin. Except for glutathione reductase (GR), all other enzymatic and non-enzymatic antioxidants were found to decrease following wounding. The decrease was 60-70% in superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) at 2, 4 and 7 days, while in the case of catalase (CAT) the decrease was 40-60% during this period. Although a complete recovery in the activity of CAT was observed, SOD and GPx did not recover completely and GST was found to be slightly elevated on 14th day post wounding. Non-enzymatic antioxidants viz, ascorbic acid, vitamin E and glutathione were also found to decrease to about 60-70% and except glutathione none of them was found to recover completely at 14th day postwounding. Interestingly thiobarbituric acid reactive substance (TBARS) expressed as malondialdehyde (MDA) equivalent, a marker of lipid peroxidation, decreased following wounding which could be because of meagre availability of lipid substrate and/or of ascorbic acid. The results indicate that wounding results in loss of different free radical scavengers both enzymatic and non-enzymatic which either partially or completely recover following healing.

195 citations


Journal ArticleDOI
TL;DR: The studies proved that the aqueous form of drug (2 ml/kg) administration has more hepatoprotective activity than the powder form; this is probably due to the better absorbtion of the liquid form through the intestinal tract.

146 citations


Journal ArticleDOI
TL;DR: This first report of rIL-12-induced protection of primates against an infectious agent supports assessment of rhIL- 12 for immunoprophylaxis of human malaria.
Abstract: An estimated 300–500 million new infections and 1.5–2.7 million deaths attributed to malaria occur annually in the developing world1, and every year tens of millions of travelers from countries where malaria is not transmitted visit countries with malaria. Because the parasites that cause malaria have developed resistance to many antimalarial drugs, new methods for prevention are required. Intraperitoneal injection into mice of one dose of 150 ng (approximately 7.5 μg per kg body weight) recombinant mouse interleukin-12 (rmlL-12) 2 days before challenge with Plasmodium yoelii sporozoites protects 100% of mice against malaria2. We report that one subcutaneous injection of 10 μg/kg recombinant human IL-12 (rhIL-12) 2 days before challenge with P. cynomolgi sporozoites protected seven of seven rhesus monkeys. Protection was associated with marked increases in plasma levels of interferon-γ (IFN-γ), and relative increases of lymphoid cell messenger RNA coding for IFIM-γ and several other cytokines. We speculate that rIL-12 protects monkeys through IFN-γ-dependent elimination of P. cynomolgi-infected hepatocytes. This first report of rIL-12-induced protection of primates against an infectious agent supports assessment of rhIL-12 for immunoprophylaxis of human malaria.

137 citations


Journal ArticleDOI
TL;DR: This review has highlighted studies conducted to look for an association between HLA and infectious diseases; such studies have had a variable degree of success because the pathogenesis of different diseases varies widely, and most diseases have a polygenic etiology.
Abstract: Human leukocyte antigens (HLAs) are an inherent system of alloantigens, which are the products of genes of the major histocompatibility complex (MHC). These genes span a region of approximately 4 centimorgans on the short arm of human chromosome 6 at band p 21.3 and encode the HLA class I and class II antigens, which play a central role in cell-to-cell interaction in the immune system. These antigens interact with the antigen-specific cell surface receptors of T lymphocytes (TCR) thus causing activation of the lymphocytes and the resulting immune response. Class I antigens restrict cytotoxic T-cell (CD8+) function thus killing viral infected targets, while class II antigens are involved in presentation of exogenous antigens to T-helper cells (CD4+) by antigen presenting cells (APC). The APC processes the antigens, and the immunogenic peptide is then presented at the cell surface along with the MHC molecule for recognition by the TCR. Since the MHC molecules play a central role in regulating the immune response, they may have an important role in controlling resistance and susceptibility to diseases. In this review we have highlighted studies conducted to look for an association between HLA and infectious diseases; such studies have had a variable degree of success because the pathogenesis of different diseases varies widely, and most diseases have a polygenic etiology.

59 citations


Journal ArticleDOI
TL;DR: Energy dependence, involvement of –SH group, and noninterference by amino acid, spermidine, and spermine in the putrescine influx process clearly demonstrate the presence of a distinct transporter for putrecine in infected erythrocytes.

43 citations


Journal ArticleDOI
TL;DR: Pippali Rasayana (PR), an Indian ayurvedic drug prepared from Palash and Piperaceae, was administered to patients suffering from giardiasis with clinical signs and symptoms, and stools positive for trophozoites/cysts of Giardia lamblia and there was a marked improvement in the clinical and haematological profile of the patients.

43 citations


Journal ArticleDOI
TL;DR: Results of in vivo SCE assays indicate that these three drugs are weakly genoxic in bone marrow cells of mice, the first report of the Ames mutagenicity assay for ketoprofen and in vitro SCE assay for three drugs.
Abstract: The mutagenicity of three propionic acid derivatives, namely ibuprofen, ketoprofen and naproxen, was tested in the Ames mutagenicity assay (in strains TA97a, TA100 and TA102) and in vivo genotoxicity was tested by sister chromatid exchange (SCE) in bone marrow cells of mice. These are the anti-inflammatory drugs frequently used in different parts of the world. Mutagenicity results showed no mutagenic effects in strains TA97a, TA100 and TA102 for all three drugs. Results of in vivo SCE assays indicate that these three drugs are weakly genoxic in bone marrow cells of mice. This is the first report of the Ames mutagenicity assay for ketoprofen and in vivo SCE assay for three drugs.

43 citations


Journal ArticleDOI
TL;DR: A series of highly functionalized thiophene and thieno[3,2-c]pyran-4-one derivatives have been synthesized and evaluated for their antileishmanial and antifungal activities as mentioned in this paper.

40 citations


Journal ArticleDOI
TL;DR: In this paper, Yeast strains belonging to the genera Saccharomyces and Candida have been found to be more efficient l -phenylacetylcarbinol ( l -PAC) producers as compared to other yeasts.

38 citations


Journal ArticleDOI
TL;DR: Guggulsterone significantly protected LDL apoprotein as measured by reversal of REM after oxidation, and may be due to its free radical scavenging property as this compound significantly inhibited the generation of hydroxyl radicals in a nonenzymic system.
Abstract: The oxidation of low density lipoprotein (LDL) induced by Cu+2 caused marked oxidative changes in the lipid and protein constituents of this lipoprotein in vitro Guggulsterone prevented the generation of lipid peroxides measured as thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes This compound protected LDL against depletion of lipid constituents such as cholesterol, cholesterol esters, triglyceride and phospholipids as well as inhibiting the conversion of cholesterol into oxygenated cholesterols Oxidized LDL containing less apoprotein B with a high protein carbonyl value, was more electronegative, as evidenced by the increase in relative electrophoretic mobility (REM) on agarose gel Guggulsterone significantly protected LDL apoprotein as measured by reversal of REM after oxidation The protective action of guggulsterone may be due to its free radical scavenging property as this compound significantly inhibited the generation of hydroxyl radicals in a nonenzymic system © 1997 John Wiley & Sons, Ltd

37 citations


Journal Article
TL;DR: The peritoneal environment of M. natalensis is not conducive to the development of B. malayi and this is probably related to high macrophage activity in the peritoneum of this host compared to that found in the jird.
Abstract: The fate of intraperitoneally inoculated infective third-stage larvae (L-3) of the nematode Brugia malayi Lichtenstein and the status of the peritoneal macrophage function were investigated in the susceptible rodent hosts Mastomys natalensis Roberts and Meriones unguiculatus Milne-Edwards (jird). Jirds and M, natalensis were inoculated intraperitoneally with 125 and 250 L-3 and the worm burden and peritoneal macrophage function in the two species were compared at different days post-inoculation (DPI), None of the infected M, natalensis had adult worms in the peritoneal cavity; very few degenerating L-3 surrounded by peritoneal cells were recovered 7 and 15 DPI. In contrast, all the infected jirds showed the parasite in different stages of development and the worm burden at different days PI was more in 250 L-3 dose group than in 125 L-3 dose group, The phagocytic function of peritoneal macrophages of normal M. natalensis was twice higher than that of jirds. This function was found significantly suppressed in both host species at 15 DPI; at 35 DPI, the activity was still at this low level in the jird, while that in M. natalensis reverted to uninfected age-and sex-matched control levels, These findings demonstrate that the peritoneal environment of M. natalensis is not conducive to the development of B. malayi and this is probably related to high macrophage activity in the peritoneum of this host compared to that found in the jird.

Journal ArticleDOI
TL;DR: Observations provide insights into the possible features responsible for the stabilization of intermediates in the folding of hen egg-white lysozyme.
Abstract: Equilibrium acid-induced unfolding of hen egg-white lysozyme has been investigated by a combination of optical methods, size-exclusion chromatography, and differential scanning calorimetry. The results showed the presence of a partially folded state of hen egg-white lysozyme at pH 1.5, characterized by a substantial secondary structure, a large solvent exposure of non-polar clusters, and significantly disrupted tertiary structure. A large enthalpy was also associated with the conversion of the acid-unfolded state to a fully unfolded state. Size-exclusion chromatography and 8-anilino-1-naphthalenesulphonic acid-binding studies showed an ionic-strength-induced transition of the partially folded state to a compact conformation. Furthermore, an ionic-strength-dependent aggregation on thermal unfolding of the partially folded intermediate was also observed. These observations provide insights into the possible features responsible for the stabilization of intermediates in the folding of hen egg-white lysozyme.

Journal ArticleDOI
TL;DR: PA transport systems provide the alternative pool of polyamines in L. donovani promastigotes in the absence of an adequate intracellular PA repertoire.

Journal ArticleDOI
TL;DR: Antigen derived from three major life-stages of human lymphatic filariid, Brugia malayi was fractionated by SDS-polyacrylamide gel electrophoresis and reactivity of filarial antibodies, present in sera of human bancroftian patients belonging to different categories of the disease, to immunoreactive molecules was evaluated by Western blotting and immune recognition.

Journal ArticleDOI
TL;DR: Results indicate this hexapeptide sequence represents the haem binding site of the malarial histidine-rich protein and possibly the site of nucleation for haem polymerisation.


Journal Article
TL;DR: Findings demonstrate changes in metallic ions (Magnesium, zinc, selenium and manganese) level in relation to hormonal status during menstrual cycle in women.
Abstract: Plasma concentration of metallic ions levels during menstrual cycle of twenty normally menstruating women were observed in four phases i.e. menses, follicular, ovulatory and luteal. The concentration of magnesium, zinc, selenium and manganese was highest during menses and lowest at ovulatory phase. There was rise in ionic levels of magnesium and selenium, while fall in zinc and manganese during luteal phase. Findings demonstrate changes in metallic ions (Magnesium, zinc, selenium and manganese) level in relation to hormonal status during menstrual cycle in women.

Journal ArticleDOI
TL;DR: In this paper, a special feature of some dispersion curves is their tendency to bunch in the neighborhood of the helix angle, which has been attributed to the presence of strong intramolecular interactions.
Abstract: Poly( L-methionine) (PMet) is one of the two sulfur containing polyamino acids. Raman, FTIR spectra, and heat capacity measurements of PMet have been well interpreted through the normal mode analysis and the density of states derived there- from. Earlier interpretation of heat capacity data is limited because it is based on the Tarasov model, wherein the concept of group frequency and skeletal similarity are used. A special feature of some dispersion curves is their tendency to bunch in the neighborhood of the helix angle. This has been attributed to the presence of strong intramolecular interactions. Repulsion between the dispersion curves is also observed. q 1997 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 35: 2281-2292, 1997

Journal ArticleDOI
TL;DR: A sensitive high-performance liquid chromatographic assay method in plasma has been developed and validated for the determination of picroside I in plasma and the analytical recovery of pMicroside I added to plasma was >80%.

Journal ArticleDOI
TL;DR: An association study with genetically related controls to find out whether host genetic factors like the HLA are involved in susceptibility to kala‐azar (visceral leishmaniasis) in India, found no significant evidence for association with any of the three HLA loci.
Abstract: HLA has been shown to be associated with many diseases. To find out whether host genetic factors like the HLA are involved in susceptibility to kala-azar (visceral leishmaniasis) in India, we formulated an association study with genetically related controls. All samples were typed by PCR SSOP (sequence specific oligonucleotide probes) for HLA class I (A and B) and class II (DR) antigens. The test of association we used was the transmission disequilibrium test (TDT). No significant evidence for association with any of the three HLA loci was obtained.

Journal ArticleDOI
TL;DR: It is suggested that the failure of the parasite heme detoxification system due to this reaction results in the accumulation of toxic heme, which alone, or complexed with the antimalarial leads to the death of malaria parasite.

Journal ArticleDOI
TL;DR: The findings suggest the presence and importance of heme metabolism in the de novo synthesis of different hemoproteins of the Leishmania parasite as well as the detoxification and its defence against biological insults.
Abstract: Promastigotes of Leishmania donovani (Dd-8 strain) showed presence of important key enzymes of heme synthesizing (d-aminolevulinic acid synthase and ferrochelatase) and degrading (heme oxygenase and biliverdin reductase) systems, classical leishmanicidal drugs viz allopurinol, amphotericin B, pentamidine and CDRI compound 93/202 inhibited the heme oxygenase activity of the parasite, whereas, δ-aminolevulinic acid synthase activity practically remained unaffected. The Km, Vmax ad pH values of heme oxygenase of promastigotes were found to be 1666 μM hemin, 625 nmol of bilirubin formed h-1 mg protein-1 and 7.5 respectively. The findings suggest the presence and importance of heme metabolism in the de novo synthesis of different hemoproteins of the Leishmania parasite as well as the detoxification and its defence against biological insults.

Journal ArticleDOI
TL;DR: The described protocol is well suited to situations where large quantities of antigenic protein mixtures must be processed in order to get the purified molecules/fractions in amounts required for immunoepidemiological studies.
Abstract: Integral membrane proteins (IMP) represent a serologically distinct class of mycobacterial antigens which are potent stimulators of human T cells (Mehrotra et al., Clin Exp Immunol 1995; 102:626). The range of IMP from Mycobacterium fortuitum was resolved by continuous elution SDS-PAGE to recover 31 discrete fractions covering bands up to approximately 58 kD. The fractions, after removal of SDS, were subjected to human T cell proliferation assays for the identification of immunodominant molecule(s). A low molecular weight (<20kD) fraction was able to stimulate T cells from 11 out of 12 donors comprising mainly tuberculoid leprosy patients. The described protocol is well suited to situations where large quantities of antigenic protein mixtures must be processed in order to get the purified molecules/fractions in amounts required for immunoepidemiological studies.

Journal ArticleDOI
TL;DR: Synthetic marine aplysinopsin could provide a new pharmacophore for the development of antifilarial agents and cause a significant decline in MTT reduction and 14C‐glucose uptake by adult filariids.
Abstract: CDRI Compound 92/138, a synthetic analogue of aplysinopsin, was evaluated in experimental filarial infections, Litomosoides carinii in cotton rats (Sigmodon hispidus) and Acanthocheilonema viteae in Mastomys coucha. The compound killed 63.8 and 90% of adult L. carinii and A. viteae at doses of 30 and 50 mg/kg (i.p.) respectively given for 5 days. By the oral route, at 100 mg/kg for 5 days the compound caused 50.9 and 57% mortality of adult L. carinii and A. viteae, respectively. At 200 mg/kg administered orally on days 0, 10 and 25 post-infection, it reduced establishment of adult A. viteae by 68.5%. We also found 43.7 and 37.8% effect in vivo respectively on L3 and L4 stages of A. viteae at a single dose of 250 mg/kg, p.o. The compound was active in vitro at 100 micrograms/ml concentration and caused a significant decline in MTT reduction and 14C-glucose uptake by adult filariids. Thus synthetic marine aplysinopsin could provide a new pharmacophore for the development of antifilarial agents.

Journal ArticleDOI
TL;DR: Synthesis of aminoquinoline derivatives and their in vitro effects on methemoglobin formation and meetinghemoglobin reductase activity are delineated and some of the screened compounds have shown considerable meethemoglobin toxicity.

Journal ArticleDOI
TL;DR: Two new glycosphingolipids, temnosides A and B, have been isolated from a MeOH extract of the sea urchin Temnopleurus toreumaticus by FABMS, 2D NMR, and chemical degradation studies.
Abstract: Two new glycosphingolipids, temnosides A (1) and B (2), have been isolated from a MeOH extract of the sea urchin Temnopleurus toreumaticus. The proposed structures 1-O-(β-d-glucopyranosyl)-d-(+)-(2S,3R)-2-[(2‘(R)-hydroxytricosanoyl]amido]-1,3-eicosanediol (1) and 1-O-(β-d-glucopyranosyl)-d-(+)-(2S,3R)-2-(docosanoylamido)-1,3-eicosanediol (2) were established by FABMS, 2D NMR, and chemical degradation studies.

Journal ArticleDOI
TL;DR: Triazolo[1,5-a]pyrimidine (3,6), benzoxazole (7a,b), and benzimidazole(7c) derivatives have been synthesized and evaluated for their in vitro leishmanicidal activity against L. donovani promastigotes.


Journal ArticleDOI
TL;DR: A new triterpene glycoside, scrokoelziside B, was isolated from the aerial parts of Scrophularia koelzii and characterized as 3β- O -([β- d -glucopyranosyl (1 → 2), α- l -rhamnopyrnosyl ( 1 → 3)]-β-D -fucopryanosyl(1 → 4)-β-d -glou-11.

Journal ArticleDOI
TL;DR: The assay is based on production of β-galactosidase in presence of drugs during growth and was inhibited within 4 h by frontline antimycobacterial drugs like streptomycin, rifampicin, isoniazid, ethambutol, ofloxacin, and sparfloxac in at their MICs.