Showing papers by "Central Drug Research Institute published in 1996"
Journal Article•
TL;DR: The results show that data from published knowledge can be used to provide reliable, patient level, automated risk assessment, potentially reducing the cognitive burden on physicians and helping policy makers better prepare for future needs.
Abstract: Facing the rapidly spreading novel coronavirus disease (COVID-19), evidence to inform decision-making at both the clinical and policy-making level is highly needed. Based on the results of a study by Petrilli et al, we have developed a calculator using patient data at admission to predict the risk of critical illness (intensive care unit admission, use of mechanical ventilation, discharge to hospice, or death).
We report a retrospective validation of the risk calculator on 145 consecutive patients admitted with COVID-19 to a single hospital in Israel. Of the 18 patients with critical illness, 17 were correctly identified by the model(sensitivity: 94.4%, 95% CI, 72.7% to 99.9%; specificity: 81.9%, 95% CI, 74.1% to 88.2%). Of the 127 patients with non-critical illness, 104 were correctly identified. This, despite considerable differences between the original and validation study populations.
Our results show that data from published knowledge can be used to provide reliable, patient level, automated risk assessment, potentially reducing the cognitive burden on physicians and helping policy makers better prepare for future needs.
712 citations
TL;DR: The fruits of Piper longum used in traditional remedies against intestinal distress and piperine, a pure compound, from this plant material cured 90% and 40% of rats with caecal amoebiasis, respectively.
152 citations
TL;DR: There is an apparent normalisation of the indices of oxidative stress following treatment of heart failure and a markedly improved response on vitamin E supplementation which may be more beneficial.
108 citations
TL;DR: Age, focal weakness, cranial nerve palsy and hydrocephalus were found to be contributing to the three month outcome of TBM patients as assessed by the Barthel index.
97 citations
TL;DR: It is confirmed that pinopod development on uterine luminal epithelium was dependent on progesterone alone and demonstrated that preovulatory (priming) or nidatory (endometrial sensitizing) estrogen or viable blastocysts in utero have no role in their development.
Abstract: Intrinsic role of preovulatory and nidatory estrogen and progesterone and presence of viable blastocysts in utero in pinopod development on the uterine luminal epithelial surface and correlation between time of their development and onset of endometrial sensitivity were investigated In adult rats, pinopods were observed on the entire epithelium even before secretion of nidatory estrogen, ie at 1400 h on day 4 post-coitum (pc) Apparently, their number increased, more so on the antimesometrial than the mesometrial side, at 1000 h on day 5, but were fewer and mostly collapsed at 1000 h on day 6 Pinopods on day 4 were located within epithelial depressions and foldings, but protruded from the surface on days 5 and 6 Normal pinopods were also present on day 8 pc in rats under delayed implantation, but an implantation-inducing dose of estradiol-17 beta administered about 18 h earlier caused their collapse like that on day 6 in intact rats Development and appearance of pinopods in intact or delayed rats was unaffected when native preimplantation embryos were prevented from entering the uterus Normal pinopods were seen in immature rats receiving progesterone for at least 3 days or cyproterone acetate for 4 days, but not after estradiol alone In animals receiving progesterone or priming/sensitizing estradiol in addition to progesterone, the decidual response was suboptimal, irrespective of the presence of pinopods on the day of stimulation In animals in which a condition mimicking preimplantation had been produced by suitable hormone supplementation, optimal endometrial sensitivity and decidual response were elicited, even though most pinopods appeared collapsed, resembling those on day 6 in intact rats and about 18 h after estradiol in implantation-delayed rats Findings confirm that pinopod development on uterine luminal epithelium was dependent on progesterone alone and demonstrate that: (i) preovulatory (priming) or nidatory (endometrial sensitizing) estrogen or viable blastocysts in utero have no role in their development Nidatory estrogen, instead, appears to limit pinopod development by causing their collapse; (ii) pinopod development/presence on the endometrial surface might indicate the uterus coming into a period of sensitivity rather than actually being in it and might thus serve as a useful marker of "transfer window" rather than "implantation window"; (iii) in the rat, pinopod development might serve as an alternate assay for evaluation of progestational activity of newer test agents
65 citations
TL;DR: It appears that it may be possible to finger print the biochemicals of the cell wall of M. tuberculosis in a tuberculous granuloma and thus may help in detection and diagnosis of such lesions.
Abstract: In vivo, ex vivo, and in vitro proton magnetic resonance spectroscopy was performed in 12 patients with intracranial tuberculomas with an aim of detecting the biochemical constituents of Mycobacterium tuberculosis in a granuloma. One dimensional (1D) single pulse and spin-echo sequences and 2D correlative spectroscopy were used for the ex vivo study to confirm the resonances seen on in vivo study. Spectroscopic studies of the perchloric acid and lipid extract of granuloma and M. tuberculosis were performed to look for similarity of resonance. In vivo study showed the presence of lipids at 0.9, 1.3, 2.0, 2.8 ppm, and phosphoserine at 3.7 ppm. All these resonances were confirmed on ex vivo study. In addition, distinct resonances of serine and phenolic lipids were seen on ex vivo and in vitro study of tuberculous granuloma, which have not been observed in other intracranial tumors. Lipid extract of granuloma and M. tuberculosis showed phenolic lipids at 7.1 and 7.4 ppm, a constituent of the cell wall of the bacteria in a tuberculoma. It appears that it may be possible to finger print the biochemicals of the cell wall of M. tuberculosis in a tuberculous granuloma and thus may help in detection and diagnosis of such lesions.
62 citations
TL;DR: Serum lipids were found to be lowered by guggulsterone in triton WR‐1339 induced hyperlipaemia and hypolipidaemic activity of this drug is mediated through inhibition of hepatic cholesterol biosynthesis, increased faecal bile acid excretion and enhanced plasma lecithin:cholesterol acyltransferase activity.
Abstract: The lipid lowering action of guggulsterone, the active constituent of guggulipid, has been studied in triton and cholesterol fed hyperlipaemic rats. Serum lipids were found to be lowered by gug%sterone (50 mgkg, b.w.) in triton WR-1339 induced hyperlipaemia. Chronic feeding of this drug (5 mg/kg, b.w.) in animals simultaneously fed with cholesterol (25 m%kg, b.w.) for 30 days, caused lowering in the lipid and apoprotein levels of very low density and low density lipoproteins in experimental animals. Guggulsterone activates lipolytic enzymes in plasma and liver as well as stimulated receptor mediated catabolism of low density lipoprotein. The hypolipidaemic activity of this drug is mediated through inhibition of hepatic cholesterol biosynthesis, increased faecal bile acid excretion and enhanced plasma 1ecithin:cholesterol acyltransferase activity.
58 citations
TL;DR: It is reported that no spontaneous haem polymerization occurs at physiological conditions and the product described in the study mentioned above is not haemozoin/β‐haematin (haem polymer) as characterized by us on the basis of solubility characteristics and thin layer chromatography.
56 citations
TL;DR: It is concluded that NO itself causes an increase in the permeability of BBB, however arginine-induced opening is not NO mediated, and the possibility of NO generation and its involvement in BBB permeability alteration is ruled out.
Abstract: The role of nitric oxide (NO), a well known vasodilator, in the regulation of blood-brain barrier (BBB) permeability is not clear. Therefore, the present study was planned to assess the role of NO-releasing compounds like sodium nitroprusside (SNP) and the active metabolite of molsidomine, SIN-1, as well as a precursor of NO, L-arginine, on this physiological barrier. The permeability was assessed by using several tracers. All three agents increased the permeability of BBB to the tracer. The increase in permeability caused by L-arginine was not blocked by N-nitro-L-arginine methyl ester (L-NAME). L-Arginine-treated brains did not show an elevation of nitrite content, thus ruling out the possibility of NO generation and its involvement in BBB permeability alteration. It is concluded that NO itself causes an increase in the permeability of BBB. However arginine-induced opening is not NO mediated.
51 citations
TL;DR: The lipid lowering action of the bark powder of Terminalia arjuna has been studied in triton and cholesterol fed rats and alters lipolytic activities in plasma, liver, heart and adipose tissues of hyperlipaemic rats.
Abstract: The lipid lowering action of the bark powder of Terminalia arjuna (T. arjuna) has been studied in triton and cholesterol fed rats. Serum lipids were found to be lowered by T. arjuna (100 mglkg, b.w.) in triton induced hyperlipaemia. Chronic feeding of this powder (100 mg/kg, b.w., p.o.) in animals simultaneously fed with cholesterol (25 mg/kg, b.w.) for 30 days, caused lowering in lipids and protein levels of β-lipoproteins followed by an increase in high density lipoprotein-cholesterol compared with the cholesterol fed groups. T. arjuna alters lipolytic activities in plasma, liver, heart and adipose tissues of hyperlipaemic rats. The lipid lowering action of this natural product is mediated through inhibition of hepatic cholesterol biosynthesis, increased faecal bile acid excretion and enhanced plasma lecithin:cholesterol acyltransferase activity and stimulation of receptor mediated catabolism of low density lipoprotein.
49 citations
Journal Article•
TL;DR: Alcoholics extracts of 266 botanically identified plant materials from 222 plant species have been tested for various biological activities including chemotherapeutic and pharmacological screenings and the active principles and results are reported.
Abstract: Alcoholics extracts of 266 botanically identified plant materials from 222 plant species have been tested for various biological activities including chemotherapeutic and pharmacological screenings. Biological activities have been observed in 89 extracts. Follow-up studies have been carried out in some plants with confirmed activity. The active principles and results of these studies are reported.
Journal Article•
TL;DR: It is concluded that CP is more effective than SWI (P < 0.01) and TB, however, SWI an impure natural product showed better blood sugar lowering than tolbutamide which is a drug in use.
Abstract: The mechanism of dose-dependent hypoglycemic effect, the margin of safety and ED50 of three structurally unrelated compounds, tolbutamide (TB), centpiperalone (CP) and a swerchirin-containing fraction (SWI) from the plant Swertia chirayita, were investigated in experimental models After a single oral administration of TB, CP and SWI to groups of normal and streptozotocin (STZ)-induced mild and severe diabetic rats, the blood sugar lowering effect and ED50 of the agents were determined Plasma Immuno Reactive Insulin (IRI) levels and the degree of islet beta cell degranulation were assayed using RIA and histochemical staining, respectively, in normal rats treated with the agents The percent blood sugar lowering, increase in IRI levels and beta cell degranulation were highest in CP treated normal rats (69, 124 and 75%, respectively) In addition, CP was the only agent found active in STZ-induced severely diabetic rats (P < 001) In STZ-mild diabetic rats, however, TB was more effective than CP and SWI By analysis of data using Anova method, it is concluded that CP is more effective than SWI (P < 001) and TB However, SWI an impure natural product showed better blood sugar lowering than tolbutamide which is a drug in use
TL;DR: Out of these six salicylic acid derivatives tested, only diflunisal and niclosamide showed genotoxicity as measured by both SCE and CA assays, respectively, only at the highest dose tested.
Abstract: In vivo sister chromatid exchange (SCE) and chromosome aberrations (CA) were carried out for six salicylic acid derivatives in bone marrow cells of mice. Six salicylic acid derivatives, namely acetyl salicylic acid (aspirin), salicylic acid, salicylamide, sodium salicylate, diflunisal and niclosamide, were used for these experiments. Drugs were administered both intraperitoneally (i.p.) and orally by gavage. Out of these six salicylic acid derivatives tested, only diflunisal and niclosamide showed genotoxicity as measured by both SCE and CA assays. Acetyl salicylic acid and sodium salicylate showed weak genotoxicity as measured by SCE and CA, respectively, only at the highest dose tested.
TL;DR: In this article, a one-step synthesis provided the cyclopeptides 1 - 4 (n= 2 - 5) composed of repeating adamantane and L-cystine units.
Abstract: A one-step synthesis provided the cyclopeptides 1 - 4 (n= 2 - 5) composed of repeating adamantane and L-cystine units. These macrocycles assume a cavitand-like conformation, in which the interior is hydrophilic and the periphery hydrophobic. Consequently, they can transport Na + and K + ions selectively in model membranes.
TL;DR: Bisbenzyl pentamidine and biscyclopropylpentamidine were identified as considerably more potent inhibitors of growth and arginine transport function of leishmania promastigotes in vitro than the parent drug, pent amidine.
TL;DR: In the present review, this work has attempted to evaluate and update the mutagenic and genotoxic effects of four of the most commonly used benzodiazepines, i.e., chlordiazepoxide (CDZ), diazepam (DZ), nitrazepam (NZ) and oxazepams (OZ) based on available literature.
Abstract: Benzodiazepines are a group of drugs which have been extensively used for their activities as an anti-anxiety, sedative, muscle relaxant and anti-convulsant. Benzodiazepines at present are the most commonly prescribed drugs. Some of these drugs are teratogenic and also carcinogenic in experimental animals. The wide human exposure to this group of drugs throughout the world is of great concern for human health. In the present review, we have attempted to evaluate and update the mutagenic and genotoxic effects of four of the most commonly used benzodiazepines, i.e., chlordiazepoxide (CDZ), diazepam (DZ), nitrazepam (NZ) and oxazepam (OZ) based on available literature.
TL;DR: Intraperitoneal administration of fenvalerate in male rats for 45 days in doses of 100 and 200 mg/kg body weight/day induced hyperexcitability, tremors and paralysis.
Journal Article•
TL;DR: Reversed-phase HPLC, coupled with fluorescence detector, was used for simultaneous determination of centchroman and DMC in biosamples and was found to be reliable and reproducible.
Abstract: This study reports assay methodology, tissue distribution, and the basic pharmacokinetic behavior of centchroman and its 7-desmethyl metabolite [7-desmethyl centchroman (DMC)] after a single 12.5 mg/kg po dose in young female rats. Plasma, liver, lung, spleen, uterus, and adipose tissue were collected at various time intervals up to 14 days after dose. Reversed-phase HPLC, coupled with fluorescence detector, was used for simultaneous determination of centchroman and DMC in biosamples. The drug and metabolite were quantitated up to 2 and 5 ng/ml in plasma and 10 and 20 ng/g in tissues, respectively. The assay method was validated in terms of accuracy, precision, interassay, and intraassay variability, and was found to be reliable and reproducible. Peak centchroman levels in all of the tissues were found between 8-12 hr, whereas DMC peaks appeared between 8 and 24 hr, except that in liver the first peak of 1.2 micrograms/g appeared in the 1-hr sample. Tissue-to-plasma concentration ratios of centchroman were > 200 times in the lung; > 100 times in the spleen, liver, and adipose tissue; and > 40 times in the uterus at maxima in each tissue. Similarly, tissue concentrations of DMC were > 350 times in the lung, > 100 times in the liver and spleen, and > 25 times in the uterus and adipose tissue than in the plasma. High tissue-to-plasma concentration ratios of metabolites than the parent drug are indicative of its greater affinity for tissues. Terminal half-life of the centchroman and DMC in plasma were 24.1 and 36.6 hr, respectively. The mean residence time of centchroman was highest in the liver (78.4 hr), followed by the uterus (72.7 hr), adipose tissue (47.5 hr), lung (46 hr), spleen (44.1 hr), and plasma (37.7 hr). The mean residence time of DMC was also highest in the liver (133.7 hr), followed by the uterus (122 hr), adipose tissue (85.2 hr), lung (62.6 hr), spleen (62.6 hr), and plasma (48.2 hr).
TL;DR: Inhibition in endometrial sensitivity by post-coital centchroman was associated with a marked depletion in uterine cytosolic ER and an increase in nuclear ER concentration, a decrease in POD and G-6-PDH activities, compact fibroblastic stroma, an increases in luminal epithelial cell height and straightening of intercellular membranes.
TL;DR: In this paper, symmetrical, unsymmetrical and hetero-aryl terphenyls were synthesized from 6-aryl-3methoxy-carbonyl-4-methylthio-2H-pyran-2-ones.
TL;DR: The syntheses of 5-amino and 5,8-diamino isoquinoline derivatives and some of the screened compounds have shown promising filaricidal response against Acanthocheilonema viteae in rodents.
TL;DR: While the smaller and slightly bigger cells showed moderate growth the larger ones had extensive growth and were seen to acquire different shapes on extending the duration of culture, such as fusiform, dumb‐bell, polygonal, rectangular or flowery.
Abstract: The method of isolation of trophoblast cell types from ectoplacental cone of hamster embryo of day 8 post coitum (plug day as day 1) and examination of their growth pattern in vitro is presented in this study. Based on their size, three types of trophoblast cells were identified. (1) the smaller cells having clear cytoplasm formed the major portion (70% to 80%) of the total cell population (2) moderately bigger cells having mono or binucleated appearance and containing minute granules in the nuclear region formed 5% to 10% and (3) extra large and multinucleated cells shared 10% to 20% of the total cell number. While the smaller and slightly bigger cells showed moderate growth the larger ones had extensive growth and were seen to acquire different shapes on extending the duration of culture, such as fusiform, dumb-bell, polygonal, rectangular or flowery. The extremities of the cytoplasmic growth of these cells were seen to be thickened at one end giving the impression of a pad-like structure. The significance of these adaptations are not known at present.
TL;DR: A highly enantioselective epoxidation of functionalized and unfunctionalized olefins using m-chloroperbenzoic acid in liposomised form (LIP MCPBA) has been demonstrated in this article.
TL;DR: Scrokoelziside A, isolated from the aerial parts of Scrophularia koelzii was shown to be 3-O-([alpha-L-rhamnopyranosyl]-13 beta,28-epoxyolean-11-en-23-ol, on the basis one- and two-dimensional NMR homo- and hetero-nuclear spectroscopic evidence.
TL;DR: The purification and immunochemical characterization of a major 23 kDa cytosolic protein antigen of the vaccine candidate Mycobacterium habana induced, in a dose-related manner, skin delayed hypersensitivity in guinea-pigs and lymphocyte proliferation in BALB/c mice primed with M. habANA, and induced lymphocyte proliferative responses in human subjects comprising tuberculoid leprosy patients and healthy contacts.
Abstract: This study describes the purification and immunochemical characterization of a major 23 kDa cytosolic protein antigen of the vaccine candidate Mycobacterium habana (TMC 5135). The 23 kDa protein alone was salted out from the cytosol at an ammonium sulfate saturation of 80-95%. It represented about 1.5% of the total cytosolic protein, appeared glycosylated by staining with periodic acid/Schiff's reagent, and showed a pl of approximately 5.3. Its native molecular mass was determined as approximately 48 kDa, suggesting a homodimeric configuration. Immunoblotting with the WHO-IMMLEP/IMMTUB mAbs mc5041 and IT61 and activity staining after native PAGE established its identity as a mycobacterial superoxide dismutase (SOD) of the Fe/Mn type. The sequence of the 18 N-terminal amino acids, which also contained the binding site for mc5041, showed a close resemblance, not only with the reported deduced sequences of Mycobacterium leprae and Mycobacterium tuberculosis Fe/MnSODs, but also with human MnSOD. In order to study its immunopathological relevance, the protein was subjected to in vivo and in vitro assays for T cell activation. It induced, in a dose-related manner, skin delayed hypersensitivity in guinea-pigs and lymphocyte proliferation in BALB/c mice primed with M. habana. Most significantly, it also induced lymphocyte proliferative responses, in a manner analogous to M. leprae, in human subjects comprising tuberculoid leprosy patients and healthy contacts.
TL;DR: Prophylatic treatment with a single dose of polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose, a potent interferon inducer and immune enhancer, completely abolished the infectivity of sporozoites and had no protective effect against trophozoite-induced infection.
Abstract: Prophylatic treatment with a single dose of 1.0 or 2.0 mg/kg (body weight) of polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (Poly ICLC), a potent interferon ...
TL;DR: It was observed that AP and τ‐GT registered marked increase in aged rats, and lactate dehydrogenase activity decreased with the increasing age, while Monoamine oxidase A activity in the microvessels decreased with age whereas MAO‐B moved in the reverse direction.
TL;DR: The results obtained indicate that the attenuation of the LCL response by L‐ and D‐enantiomers of arginine analogues, is a non‐specific effect as there was no inhibition of NADPH‐oxidase and MPO activity, MPO release or oxygen consumption.
Abstract: 1. Formyl-methionyl-leucyl-phenylalanine (FMLP) or arachidonic acid (AA) induced luminol dependent chemiluminescence (LCL) response of rat polymorphonuclear leukocytes (PMNLs) was found to be inhibited by nitric oxide synthease inhibitors and their D-enantiomers. 2. Rat PMNLs LCL response was inhibited by NG-nitro-L-arginine methyl ester (L-NAME), D-NAME, NG-monomethyl-L-arginine (L-NMMA) or D-NMMA, in a concentration- and time-dependent manner. 3. It was observed that both L- and D-enantiomers of the arginine analogues (1000 microM) did not inhibit AA induced lucigenin-dependent chemiluminescence (LUCDCL) response and cytochrome c reduction, used for estimating the NADPH-oxidase activity in the cells and in the cell free system, respectively. 4. None of the L- and D-enantiomers had any effect on either rat basal PMNLs or AA-induced oxygen consumption. 5. In addition, neither the L nor D-enantiomers of NAME altered either AA-induced release or the activity of myeloperoxidase from rat PMNLs azurophilic granules. 6. The results obtained indicate that the attenuation of the LCL response by L- and D-enantiomers of arginine analogues, is a non-specific effect as there was no inhibition of NADPH-oxidase and MPO activity, MPO release or oxygen consumption. Therefore, the data obtained indicate that these agents should be used with caution to analyse the role of nitric oxide in rat PMNLs LCL response.
TL;DR: In this paper, a complete study of normal modes and their dispersion in the unusual left-handed polypeptide form is presented, where a special feature of some of the dispersion curves is their tendency to bunch in the neighborhood of helix angle.
Abstract: SYNOPSIS Poly(P-benzyl-L-aspartate) (PBLA) is an unusual polypeptide, which is capable of going into four different conformations, namely, left-handed a helix, right-handed a helix, o helix, and fi pleated sheet. The present work is a complete study of normal modes and their dispersion in the unusual left-handed a form. A special feature of some of the dispersion curves is their tendency to bunch in the neighborhood of helix angle. This is attributed to the presence of strong intramolecular interactions. Crossing and repulsion between the dispersion curves is also observed. The N-deuterated analogue of PBLA has been studied to check the validity of assignments and force field (Urey Bradley). Specific heat has been obtained from dispersion curves via density of states. A comparative study of left-handed and right-handed forms is presented. 0 1996 John Wiley & Sons, Inc.
TL;DR: During in vitro transformation, Leishmania donovani promastigotes converted into amastigote‐like forms and underwent several changes in membrane parameters, implying the presence of specific glycoconjugates on the parasite surface.
Abstract: During in vitro transformation, Leishmania donovani promastigotes converted into amastigote-like forms and underwent several changes in membrane parameters. They exhibited significantly increased microviscosity comparable to true amastigotes. Activities of several functionally important membrane bound enzymes were also altered, thereby indicating a change in their orientation. Peanut agglutinin was found to be specific for agglutination of stationary phase promastigotes whereas wheat-germ agglutinin was specific for the amastigote-like forms as well as for pure amastigotes, implying the presence of specific glycoconjugates on the parasite surface.