PubMed Health⌕ Search

Biomedical subjects

M P Gupta

Publications and source records attributed to M P Gupta.

At least 55 records · Page 3Linked to original sources

Natural product drug discovery and development: new perspectives on international collaboration.

Until recently, the prevailing attitude in developed nations regarded the world's genetic resources, which are mainly concentrated in the developing world, as a common resource of humankind, to be exploited freely irrespective of national origin. With the devastation being wreaked in the tropical rainforests and the resurgence in interest in recent years in the discovery of novel drugs from natural sources, particularly plants and marine organisms, the international scientific community has realized that the conservation of these global genetic resources and the indigenous knowledge associated with their use are of primary importance if their potential is to be fully explored. With this realization has come a recognition that these goals must be achieved through collaboration with, and fair and equitable compensation of, the scientists and communities of the genetically rich source countries. The signing of the United Nations Convention on Biological Diversity by nearly all of the World's nations has emphasized the need for the implementation of such policies. In this review, the articles of the Convention of relevance to the activities and practices of the natural products scientific community are briefly discussed. This discussion is followed by a summary of policies for international collaboration and compensation being implemented by several developed country organizations, and the perspectives on the current developments given by representatives of some of the source countries located in the regions of greatest biodiversity.

Bioethics↗

Bio-active compounds from Psychotria camponutans.

A new benzoquinone (1-hydroxybenzoisochromanquinone) and benz [g]isoquinoline-5, 10-dione have been isolated from the woody parts of Psychotria camponutans, as a result of bioactivity-guided fractionation. The compounds were characterized by UV, IR, EI-mass, 1H-, and 13C-NMR, and HETCOR NMR spectroscopy. Both compounds, together with acetylbenzoisochromanquinone, showed in vitro strong activity against brine shrimp, KB cells, and chloroquine-resistant P. falciparum.

Animals↗

Antifungal principles of Baccharis pedunculata.

Four compounds including a flavone, an acetylenic lactone, a prenylated coumarin, and a 3-methyl ether flavone were isolated from the dichloromethane leaf extract of Baccharis pedunculata (Mill.) Cabr. (Asteraceae). The latter three compounds were identified to be responsible for the antifungal activity against some human pathogenic and phytopathogenic fungi. The most active compound, lachnophyllum lactone, an acetylenic lactone, showed a very high toxicity (LD50 2 micrograms/ml) against human keratinocytes.

Antifungal Agents↗

Substituted quinazolinones and their anti-inflammatory activity.

6-Substituted-2-alkyl-3-(4-aminobenzene sulphonamido)quinazolin-4-(3H) ones (1a-b) were converted either to 2-methyl 3-[(N-aminoacylbenzoate)benzenes sulphonamido]quinazolin-4 (3H) ones (2a-c) or to 6-substituted-2-alkyl-3-(N-arylidene benzene sulphonamido)-quinazolin-4- (3H) ones (3a-h). 3 on reduction, yielded 6-substituted-2-alkyl-3-(N-arylmethyl sulphonamido)-quinazolin-4(3H)ones (4a-l). Reaction of 3a-h with thioglycolic acid afforded 2-alkyl-3-[4'-(5'-arylthiazolidin-3'-one)benzene sulphonamido]quinazolin-4(3H)ones (5a-h). All these compounds were evaluated for their anti-inflammatory activity against carrageenin induced rat's paw oedema. Active compounds were also evaluated for ulcerogenic liability and ALD50 values.

Animals↗

An E-box/M-CAT hybrid motif and cognate binding protein(s) regulate the basal muscle-specific and cAMP-inducible expression of the rat cardiac alpha-myosin heavy chain gene.

Expression of the cardiac myosin heavy chain (MHC) genes is regulated developmentally and by numerous epigenetic factors. Here we report the identification of a cis-regulatory element and cognate nuclear binding protein(s) responsible for cAMP-induced expression of the rat cardiac alpha-MHC gene. By Northern blot analysis, we found that, in primary cultures of fetal rat heart myocytes, the elevation of intracellular levels of cAMP results in up-regulation of alpha-MHC and down-regulation of beta-MHC mRNA expression. This effect of cAMP was dependent upon the basal level of expression of both MHC transcripts and was sensitive to cycloheximide. In transient expression analysis employing a series of alpha-MHC/CAT constructs, we identified a 31-base pair fragment located in the immediate upstream region (-71 to -40), which confers both muscle-specific and cAMP-inducible expression of the gene. Within this 31-base pair fragment there are two regions, an AT-rich portion and a hybrid motif which contains overlapping sequences of E-box and M-CAT binding sites (GGCACGTGGAATG). By substitution mutation analysis, both elements were found important for the basal muscle-specific expression; however, the cAMP-inducible expression of the gene is conferred only by the E-box/M-CAT hybrid motif (EM element). Using mobility gel shift competition assay, immunoblotting, and UV-cross-linking analyses, we found that a protein binding to the EM element is indistinguishable from the transcription enhancer factor-1 (TEF-1) in terms of sequence recognition, molecular mass, and immunoreactivity. Methylation interference and point mutation analyses indicate that, besides M-CAT sequences, center CG dinucleotides of the E-box motif CACGTG are essential for protein binding to the EM element and for its functional activity. Furthermore, our data also show that, in addition to TEF-1, another HF-1a-related factor may be recognized by the alpha-MHC gene EM element. These results are first to demonstrate transcriptional activation of a sarcomeric gene by cAMP and support the role of TEF-1 and HF-1a-like factors in the regulation of alpha-MHC gene expression in cardiac myocytes.

Animals↗

Demonstration of glutathione peroxidase in rat liver peroxisomes and its intraorganellar distribution.

Earlier, we reported that rat liver peroxisomes contain Cu-Zn superoxide dismutase (J. Biol. Chem. 267, 6870), thereby suggesting a new antioxidant role for this organelle in free radical metabolism. In this study, we report for the first time that mammalian peroxisomes also contain glutathione peroxidase. Using highly purified rat liver peroxisomes isolated by Nycodenz gradient, we found that peroxisomes contain glutathione peroxidase which shows enzymatic activity with different substrates such as hydrogen peroxide, cumene hydroperoxide, and t-butyl hydroperoxide. This activity could be inhibited in vitro by mercaptosuccinate. Western blot analysis revealed that peroxisomes from control and ciprofibrate-treated livers show immunoreactive bands with antibodies raised against glutathione peroxidase. The intraperoxisomal distribution of glutathione peroxidase was investigated by using peroxisomal membrane and matrix proteins. The results revealed that glutathione peroxidase is a matrix enzyme. The presence of glutathione peroxidase in peroxisomes provides an alternate enzyme system responsible for the degradation of organic peroxides and the degradation of H2O2 under conditions in which catalase is inactivated (e.g., ischemia-reperfusion and endotoxemia). These findings suggest that glutathione peroxidase in peroxisomes may play a novel role in the cellular antioxidant responses to various oxidative stress conditions.

Animals↗

Pharmacological and phytochemical studies of Cephäelis axillaris.

The most significant effect, observed in the preliminary pharmacological evaluation of the whole ethanol extract and the alkaloidal fraction of Cephäelis axillaris, was the hyperemia of ears and external mucosas which was most probably due to an alpha-adrenergic blocking activity. In addition, both samples also induced a marked hypotension in normotensive as well as hypertensive (SHR) rats and inhibited the increases of blood pressure induced by i.v. administration of noradrenaline in pithed rats. The structures of the major alkaloidal components of the extract were elucidated on the basis of chemical characterization assays and IR, UV, 1H and 13C one and two-dimensional NMR analyses.

Animals↗

In-migration in Madhya Pradesh.

"The aim of this paper is to analyse the expectancy of in-migration in the districts of Madhya Pradesh State [India, using the 1981 census.].... The percentage of in-migration in Madhya Pradesh from rural areas is very high (84.83), in comparison to the urban areas (15.17). The influences of industrialisation, urbanisation and facilities of higher education on in-migration has been analysed and found significant. The Chhattisgarh Basin and Malwa Plateau are the regions where the expectancy and actual in-migration are high."

Asia↗

Denervated chicken breast muscle displays discoordinate regulation and differential patterns of expression of alpha f and beta tropomyosin genes.

The expression of the alpha fast (alpha f) and beta tropomyosin (TM) genes has been analysed with muscle-specific and common cDNA probes after unilateral nerve section of the pectoralis major muscle (PM) in 4-week-old chickens. The following were observed in denervated muscles. (1) The beta TM mRNA, which was repressed during development, reaccumulates in a biphasic curve with the increase in the beta TM protein lagging behind the changes in its mRNA. Accordingly, no beta TM is seen in products translated in vitro from total and polyA+ RNA obtained 1 week after denervation. No such translation block is seen with RNA obtained from control or muscles denervated for 6 weeks. (2) No changes in the alpha fTM mRNA and corresponding protein are observed. (3) RNA processing of the two genes is not changed. (4) In the contralateral muscles, transitory increases in alpha f and beta TM mRNAs are observed while the corresponding proteins remain unchanged. Our data suggest that muscle fibres display early and long-term responses to the loss of neural input which might result from a combination of changes produced by regenerative processes and reprogramming of existing fibres. Moreover, in contrast to normal development, no reciprocal changes of alpha f and beta TM expression are seen in denervated muscles.

Animals↗

Trypanosoma evansi infection in dogs: seasonal prevalence and chemotherapy.

A 1-year survey was undertaken to determine the incidence of Trypanosoma evansi in dogs at Ludhiana, India. Of 64 dogs examined by wet film, thin smear, thick smear and mouse inoculation, three (4.68%) were found to be positive for T. evansi. All the positive animals were detected during the rainy and post-rainy seasons. The treatment of three infected dogs with a combination of quinpyramine sulphate and chloride (3:2 w/w) resulted in complete recovery of two dogs; another dog died on the day therapy was initiated.

Animals↗

Medicinal plant inventory of Kuna Indians: Part 1.

Results of an ethnopharmacognostic survey of 90 plants used by the Kuna Indians of San Blas Islands, who live in Ailigandí, are listed. Results of a literature search are also reported, including medical uses, known constituents and pharmacological effects.

Humans↗

A microwell cytotoxicity assay using Artemia salina (brine shrimp).

A new microplate assay for cytotoxicity testing using A. salina has been developed and shown to give results comparable to a previously published test-tube method. The assay reliably detected all of the compounds toxic to KB cells in a series of 21 pharmacologically active agents, except for two which require metabolic activation in man. Four quassinoids with cytotoxic and antiplasmodial activity were also toxic to the brine shrimp while quassin itself was inactive in all three systems. It is proposed that this assay provides a convenient means by which the presence of cytotoxic quassinoids may be detected during the fractionation of plant extracts.

Animals↗

[The analgesic and anti-inflammatory effects of Drymonia serrulata (Jacq.) Mart].

The authors experimentally demonstrated that an aqueous fraction of Drymonia serrulata (Jacq.) Mart. has peripheral, but not central, analgesic activity, and that it also has a dose-dependent anti-inflammatory activity at 24 and 96 hours. The experimental results indicate that the etnomedical use of this plant by the Guaymi Indians may have some scientific validity

Animals↗

Isolation and characterization of a rat ventricular cDNA expressed specifically in cardiac and skeletal muscles.

We describe the isolation of a novel cDNA named Myomy and show that its transcripts are present in skeletal and cardiac muscles as well as in differentiated Sol 8 skeletal muscle cell line. Sequence analysis revealed that neither nucleotides nor deduced protein product have any significant homology to those previously described. The encoded protein of Myomy cDNA consists of 76 amino acids and has a molecular weight of 8,000 dalton. Based on its muscle specific expression, low abundance and a higher occurrence of SP(T)XX, S(T)S(T)XX motifs, we suggest that Myomy encodes a new muscle specific transcription factor.

Amino Acid Sequence↗

(+)-4 beta-hydroxyhernandulcin, a new sweet sesquiterpene from the leaves and flowers of Lippia dulcis.

From the leaves and flowers of Lippia dulcis collected in Panama, a new sweet sesquiterpene identified as (+)-4 beta-hydroxyhernandulcin [2] was isolated, accompanied by (+)-hernandulcin [1], (-)-epihernandulcin [3] (a novel natural product), and 6-methyl-5-hepten-2-one [4]. Acteoside (verbascoside) [5], a known bitter phenylpropanoid glycoside, was isolated from the flowers of L. dulcis. The structure of (+)-4 beta-hydroxyhernandulcin was established by interpretation of its spectral data.

Panama↗

Egr-1, a serum-inducible zinc finger protein, regulates transcription of the rat cardiac alpha-myosin heavy chain gene.

Egr-1 is an early growth response gene that encodes a protein with three zinc fingers and is involved in transcriptional regulation. In adult heart myocytes, in contrast to c-fos and c-myc, high levels of Egr-1 mRNA expression have been shown. Here we report that Egr-1 transactivates rat cardiac alpha-MHC gene expression. In serum-starved primary cultures of 18-day-old fetal rat heart myocytes, addition of serum evoked expression of both Egr-1 and alpha-MHC gene transcripts. Inclusion of 10 microM cycloheximide in these cultures for 48 h caused a greater increase in Egr-1 mRNA, whereas the expression of alpha-MHC transcripts was ablated. To examine the involvement of Egr-1 in alpha-MHC induction, we transfected primary cultures of cardiac myocytes with plasmids pCMVEgr-1 (Egr-1 expression vector) and pMP3.3CAT containing -2.9- to +0.42-kilobase sequences of the alpha-MHC gene fused to the coding region of the chloramphenicol acetyltransferase (CAT) gene. Cotransfection of pCMVEgr-1 stimulated expression of pMP3.3CAT 10-15-fold. Furthermore, pCMVEgr-1 also stimulated expression of the endogenous alpha-MHC gene in primary cultures of cardiac myocytes. Transactivation of pMP3.3CAT expression by pCMVEgr-1 was also observed by transfecting the myogenic cell line Sol 8, but not in L6E9 cells or in NIH3T3 fibroblasts. By creating progressive 5' deletions of the alpha-MHC gene, we found that the region extending between -1698 and -1283 base pairs is necessary for Egr-1-induced expression of the alpha-MHC/CAT construct. These results define a physiological target for the Egr-1 transcription factor and delineate a novel mechanism for regulation of the alpha-MHC gene.

Animals↗

Activation of alpha-myosin heavy chain gene expression by cAMP in cultured fetal rat heart myocytes.

The effect of cAMP on cardiac myosin heavy chain (MHC) gene expression in primary cultures of 18-day-old fetal rat heart myocytes was investigated. When myocytes were treated with either 10 microM forskolin or 1 mM 8-bromo-cAMP for 48 h, the relative amount of the V1 to -V3 myosin isoform ratio increased 3-fold. The abundance of alpha-MHC mRNA was also increased 3-to-4-fold in forskolin treated vs control cells. However, no appreciable change was observed in the level of beta-MHC mRNA. In addition, a 70% increase in the transcription rate of the cardiac MHC gene was observed by nuclear run-on assay following treatment of cells with 10 microM forskolin for 12 h. These results demonstrate the preferential induction of alpha-MHC mRNA by cAMP which is, in part, mediated by transcriptional activation of the gene.

8-Bromo Cyclic Adenosine Monophosphate↗