Search PubMed⌕ Search

Biomedical subjects

S Chandra

Publications and source records attributed to S Chandra.

At least 37 records · Page 2Linked to original sources
PubMed2001

Anti-inflammatory activity of Syzygium cumini bark.

The ethanolic extract of the bark of Syzygium cumini was investigated for its anti-inflammatory activity in animal models. The extract did not show any sign of toxicity up to a dose of 10.125 g/kg, p.o. in mice. Significant anti-inflammatory activity was observed in carrageenin (acute), kaolin-carrageenin (subacute), formaldehyde (subacute)-induced paw oedema and cotton pellet granuloma (chronic) tests in rats. The extract did not induce any gastric lesion in both acute and chronic ulcerogenic tests in rats. Thus, the present study demonstrated that S. cumini bark extract has a potent anti-inflammatory action against different phases of inflammation without any side effect on gastric mucosa.

Animals↗
PubMed2001

Evaluation of anti-inflammatory activity of Pongamia pinnata leaves in rats.

In the present study, the anti-inflammatory activity of 70% ethanolic extract of Pongamia pinnata leaves (PLE) in acute, subacute and chronic models of inflammation was assessed in rats. Per os (p.o.) administration of PLE (300, 1000 mg/kg) exhibited significant anti-inflammatory activity in acute (carrageenin, histamine, 5-hydroxytryptamine and prostaglandin E2-induced hind paw edema), subacute (kaolin-carrageenin and formaldehyde-induced hind paw edema) and chronic (cotton pellet granuloma) models of inflammation. PLE did not show any sign of toxicity and mortality up to a dose level of 10.125 g/kg, p.o. in mice. Both acute as well as chronic administration of PLE (100, 300 and 1000 mg/kg, p.o.) did not produce any gastric lesion in rats. These results indicate that PLE possesses significant anti-inflammatory activity without ulcerogenic activity suggesting its potential as an anti-inflammatory agent for use in the treatment of various inflammatory diseases.

Administration, Oral↗
PubMed2001

Relationships between antioxidant activity, color, and flavor compounds of crystal malt extracts.

Aqueous extracts were prepared from five barley crystal malts (color range 15-440 degrees EBC, European Brewing Convention units). Antioxidant activity was determined by using the 2,2'-azinobis(3-ethylbenothiazoline-6-sulfonic acid) (ABTS(*)(+)) radical cation scavenging method. Antioxidant activity increased with increasing color value although the rate of increase decreased with increasing color value. Color was measured in CIELAB space. Extracts of the 15, 23, and 72 degrees EBC malts followed the same dilution pathway as did the 148 degrees EBC sample at higher dilution levels, indicating that they could each be used to give the same color by appropriate dilution. The 440 degrees EBC sample followed a different dilution pathway, indicating that different compounds were responsible for color in this extract. Fifteen selected volatile compounds were monitored using gas chromatography/mass spectrometry (GC/MS). Levels of methylpropanal, 2-methylbutanal, and 3-methylbutanal were highest for the 72 degrees EBC sample. When odor threshold values of the selected compounds were taken into account, 3-methylbutanal was the most important contributor to flavor. Relationships between levels of the lipid oxidation products, hexanal and (E)-2-nonenal, and antioxidant activity were complex, and increasing antioxidant activity for samples in the range of 15-148 degrees EBC did not result in reduced levels of these lipid-derived compounds. When different colored malt extracts were diluted to give the same a* and b* values, calculated antioxidant activity and amounts of 3-methylbutanal, hexanal, and (E)-2-nonenal decreased with increasing degrees EBC value.

Antioxidants↗
PubMed2001

Studies of cell division (mitosis and cytokinesis) by dynamic secondary ion mass spectrometry ion microscopy: LLC-PK1 epithelial cells as a model for subcellular isotopic imaging.

The feasibility of the renal epithelial LLC-PK1 cell line as a model for cell division studies with secondary ion mass spectrometry (SIMS) was tested. In this cell line, cells undergoing all stages of mitosis and cytokinesis remained firmly attached to the substrate and could be cryogenically prepared. Fractured freeze-dried mitotic cells showed well-preserved organelles as revealed by fluorescence imaging of rhodamine-123 and C6-NBD-ceramide by confocal laser scanning microscopy. Secondary electron microscopy analysis of fractured freeze-dried dividing cells revealed minimal surface topography that does not interfere in isotopic imaging of both positive (39K, 23Na, 24Mg, 40Ca, etc.) and negative (31P, 35Cl, etc.) secondaries with a CAMECA IMS-3f ion microscope. Mitotic cells revealed well-preserved intracellular ionic composition of even the most diffusible ions (total concentrations of 39K+ and 23Na+) as revealed by K : Na ratios of approximately 10. Structurally damaged mitotic cells could be identified by their reduced K : Na ratios and an excessive loading of calcium. Quantitative three-dimensional SIMS analysis was required for studying subcellular calcium distribution in dividing cells. The LLC-PK1 model also allowed SIMS studies of M-phase arrested cells with mitosis-arresting drugs (taxol, monastrol and nocodazole). This study opens new avenues of cell division research related to ion fluxes and chemical composition with SIMS.

Animals↗
PubMed2001

Encapsulation in cationic liposomes enhances antitumour efficacy and reduces the toxicity of etoposide, a topo-isomerase II inhibitor.

Etoposide exerts its antineoplastic effect by forming a ternary complex with topo-isomerase II and DNA, leading to DNA breaks and cell death. However, it causes myelosuppression and its lipophilicity poses a major limitation during administration. Liposomes have been reported to increase the efficacy and reduce the toxicity of antineoplastic agents. Recent evidence suggests that cationic liposomes bind efficiently to tumours. The present study was thus designed to encapsulate etoposide in cationic liposomes and to evaluate its antitumour efficacy and systemic toxicity in comparison with a conventional parenteral formulation. Etoposide encapsulated in liposomes was synthesised by thin film hydration followed by an extrusion method. Fibrosarcoma was induced in mice by subcutaneous administration of 20-methylcholanthrene. Chemotherapy was started when the tumour reached 200 mm(3) in volume. Liposomal etoposide (10 mg/m(2)/day for 5 days) significantly delayed tumour growth as compared to non-liposomal etoposide. The median time of death was calculated to be 19.5, 26.25 and 56 days in vehicle-treated controls, non-liposomal-etoposide- and liposomal-etoposide-treated groups, respectively. A transient reduction in body weight was seen in both the liposomal- and non-liposomal-etoposide-treated groups. The maximum tolerated dose was however significantly higher in the group treated with liposomal etoposide, which also exhibited a lesser degree of myelosuppression than the animals treated with non-liposomal etoposide. The present findings suggest that cationic liposomes could be considered as potential for delivery of etoposide to tumours.

Animals↗
PubMed2001

The generalization of an olfactory-based conditioned response reveals unique but overlapping odour representations in the moth Manduca sexta.

Most highly derived olfactory systems, such as the insect antennal lobe, discriminate among a wide array of monomolecular odourants and blends of odourants. Given the relatively limited number of neurons used to code these odours, this ability implies that neural representations for odours overlap in a cross-fiber coding scheme. Here we use the generalization of a conditioned feeding response in the sphinx moth, Manduca sexta, to quantify three geometry-based dimensions of odour space in which monomolecular odours may be assessed. In a series of experiments we show that generalization of a conditioned response from one monomolecular odour to another is a function of differences in length and shape of the carbon chain as well as the functional group on the molecule. When moths were conditioned to 2-hexanone or 1-decanol and tested with a number of alcohols and ketones, we found that the generalization of the conditioned response decreased as a function of the chain length and functional group. In contrast, when conditioned to 1-hexanol, moths failed to distinguish alcohols from ketones of the same chain length. In all of these cases, chain length did not interact with functional group, thus indicating the independence of these dimensions. Differential conditioning of alcohols and of alcohols and ketones revealed interaction of excitatory and inhibitory generalization gradients within an odour 'dimension'. When odourants were sufficiently distinct, the peak of the generalization gradient was shifted away from the conditioning odour and in an opposite direction from the unreinforced odour. Altogether, these data substantiate the claim that these molecular characteristics are relevant coding dimensions in the moth olfactory system. These data are consistent with a cross-fiber coding scheme in which odours are coded by spatio-temporally overlapping sets of neurons, both in the periphery and in the antennal lobes.

Alcohols↗
PubMed2001

Identification of inhibitors of DNA topoisomerase II from a synthetic library of glycoconjugates.

A library of 24 glycoconjugates related to glycosylated beta-amino acid derivative (I) was been prepared and screened against DNA topoisomerase-II of the filarial parasite S. cervi. Among these, compound 6 was found to be a potent inhibitor of DNA topoisomerase-II with 95% inhibition at 1.09 microM. Furthermore, compound 6 was at least three times more potent than the lead compound, glycosylated beta-amino acid derivative I.

Enzyme Inhibitors↗
PubMed2001

SIMS ion microscopy in cancer research: single cell isotopic imaging for chemical composition, cytotoxicity and cell cycle recognition.

A secondary ion mass spectrometry (SIMS) based isotopic imaging technique was used for studies of i/ total calcium stored in cancerous and normal cell lines and ii/ intracellular chemical composition (total K, Na, and Ca) in relation to DNA staining patterns in taxol-treated breast cancer cells. A Cameca IMS-3f ion microscope with 0.5 microm spatial resolution was used. Observations were made on frozen freeze-dried cells. In MCF-10A non-tumorigenic breast epithelial cells, the nucleus contained 0.6 +/- 0.10 mM and the cytoplasm 1.1 +/- 0.30 mM total calcium per unit volume (mean +/- S.D.). MCF-7 tumorigenic breast epithelial cells revealed an abnormal total calcium distribution. Their nuclei and cytoplasm were not significantly different in stored calcium concentrations (0.5 +/- 0.08 mM total calcium in the nucleus and 0.6 +/- 0.07 mM in the cytoplasm). Furthermore, in MCF-7 cells the cytoplasmic total calcium is significantly less than in MCF-10A cells. Both cell lines contained approximately 150 mM intracellular potassium and 13 mM sodium. As 80% of the cytoplasmic total calcium pool in MCF-10A cells could be released with thapsigargin, it is plausible that the calcium storage capacity of the endoplasmic reticulum in tumorigenic MCF-7 cells is compromised. Correlative SIMS and confocal laser scanning microscopy (CLSM) revealed an increase in intracellular sodium and a redistribution of calcium in taxol-arrested M-phase cells prior to any noticeable DNA fragmentation. This novel correlative approach opens new avenues of research for understanding intracellular ionic composition in relation to therapeutic cytotoxicity. Other valuable features of SIMS for cancer research shown in this study include subcellular imaging of calcium influx using 44Ca, 127I from iododeoxyuridine for S-phase recognition, and 19F from fluorinated deoxyglucose.

Animals↗
PubMed2000

Oxygenated chalcones and bischalcones as potential antimalarial agents.

Oxygenated chalcones (3a,b) and bischalcones (4a-j) have been synthesized and evaluated for antimalarial activity against chloroquine sensitive and resistant strains of Plasmodium berghei in mice. Some of the screened compounds, 3a, 4c, 4e, 4f and 4i, have shown significant activity at 100 mg/kg dose against sensitive strain.

Animals↗
PubMed2000

Direct reversal of DNA damage by mutant methyltransferase protein protects mice against dose-intensified chemotherapy and leads to in vivo selection of hematopoietic stem cells.

Direct reversal of O6 adducts caused by chemotherapy agents is accomplished in mammalian cells by the protein O6-methylguanine DNA methyltransferase (MGMT). Some tumors overexpress MGMT and are resistant to alkylator therapy. One future approach to treatment of these tumors may rely on concurrent pharmacological depletion of tumor MGMT with O6-benzylguanine (6-BG) and protection of sensitive tissues, such as hematopoietic stem and progenitor cells, using genetic modification with 6-BG-resistant MGMT mutants. We have used retroviral-mediated gene transfer to transduce murine hematopoietic bone marrow cells with MGMT point mutants showing resistance to 6-BG depletion in vitro. These mutants include proline to alanine and proline to lysine substitutions at the 140 position (P140A and P140K, respectively), which show 40- and 1000-fold resistance to 6-BG compared with wild-type (WT) MGMT. Lethally irradiated mice were reconstituted with murine stem cells transduced with murine stem cell virus retrovirus expressing each mutant, WT MGMT, or mock-infected cells and then treated with a combination of 30 mg/kg 6-BG and 10 mg/kg 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or with 40 mg/kg BCNU alone. Compared with mice treated with BCNU alone, significant myeloid toxicity and death occurred in mice reconstituted with mock-infected or WT MGMT (<0.1 probability of survival) or the P140A mutant (0.13 probability of survival) MGMT cDNAs. In contrast, after an initial period of mild cytopenia, mice reconstituted with the P140K mutant (0.83 probability of survival) recovered nearly normal blood counts, even during continued treatment. Comparison of peripheral blood neutrophils after completion of 5 weekly treatments in these animals showed a direct correlation between the treatment and in vivo selection for progeny of transduced cells (pretreatment, approximately 8-12% transduced cells; no treatment, approximately 6% transduced cells; BCNU only, 51% transduced cells; 6-BG/BCNU, 93% transduced cells). To determine whether this selection occurred at the stem cell level, bone marrow from each treatment group was infused into secondary recipients. Whereas animals that received bone marrow from untreated animals reconstituted with 2% transduced cells, animals receiving marrow from 6-BG/BCNU-treated animals reconstituted with 94% transduced cells, demonstrating nearly complete selection for stem cells in the primary animals. Mice reconstituted with marrow from animals treated with BCNU only demonstrated 23% transduced cells, consistent with partial selection of stem cells in the primary mice. The levels of transduced cells also correlated with survival during a second round of intensive combination chemotherapy (probability of survival: 6-BG/BCNU, 1.0; BCNU alone, >0.70; no treatment, <0.1). These data demonstrate that mutant MGMT expressed in the bone marrow can protect mice from time- and dose-intensive chemotherapy and that the combination of 6-BG and BCNU leads to uniform selection of transduced stem cells in vivo in mice.

3T3 Cells↗
PubMed2000

Micropropagation of Dev-ringal

An efficient protocol for in vitro propagation of Thamnocalamus spathiflorus (Trin.) Munro, an evergreen temperate bamboo, through multiple shoot formation from zygotic embryos excised from germinating seeds, as well as from nodal explants taken from a 2-year-old plant has been developed. Multiple shoot formation was standardized in both the cases on Murashige and Skoog (MS) medium supplemented with 5.0 µM 6-benzylaminopurine (BAP) and 1.0 µM indole-3-butyric acid (IBA). Clumps of three to four microshoots when transferred to plant growth regulator-free medium following 14 days' initial culture on medium supplemented with 150.0 µM IBA, resulted in 100% rooting with five to 12 roots per rooted plant. Then, 18 months following the transfer of in vitro propagated plants into earthen pots containing soil and growth under outdoor conditions, gas and water vapour exchange rates were measured at different light levels (0, 100, 500, 1000, 1500, 2000 µmol(-2) s(-1)), and compared with seedlings of the same age. Light optima for photosynthesis were recorded approximately 1000 µmol m(-2) s(-1) in in vitro propagated plants as well as seedlings. Water use efficiency increased with increase in the light intensity up to 1000 µmol m(-2) s(-1) and then decreased subsequently at higher light intensities. Stomatal conductance and transpiration also increased with the increase in light intensity up to 2000 µmol(-2) s(-1). Intercellular CO(2) concentration (C(i)) and the ratio of intercellular CO(2) concentration to ambient CO(2) (C(i)/C(a)) decreased with the increase in light intensity up to 500 µmol(-2) s(-1) and then reached nearly constant levels at higher light intensities. The results show that in vitro propagated and hardened plants of T. spathiflorus are morphologically as well as functionally comparable to seed raised plants of the same age, within the limits of this study.

Journal Article↗
PubMed2000

Homologous and heterologous desensitization and synergy in pathways leading to the soybean oxidative burst.

Because the H2O2 and O2- generated during a pathogen-triggered oxidative burst could either protect or destroy a besieged plant cell, their synthesis might be expected to be tightly regulated. We have examined the nature of this regulation as it is communicated between homologous and heterologous oxidative-burst pathways, using both chemical (oligogalacturonic acid, harpin, fensulfothion) and mechanical (osmotic stress) stimuli to induce the burst. We report here that the above three chemical elicitors attenuate a subsequent oxidative burst induced in cultured soybean (Glycine max L.) cells by either the same (homologous desensitization) or a different chemical elicitor (heterologous desensitization). Further, when the magnitude of the initial oxidative burst is maximal, the cells remain refractory to subsequent elicitation for at least 10 min and then revive their sensitivities to re-stimulation with a half-time of >20 min. Mechanical stimulation of the oxidative burst appears to be regulated by a different set of constraints. Although initiation of a mechanically induced burst leads to attenuation of a subsequent mechanically induced burst, the same mechanical stimulus is peculiarly unable to reduce a subsequent chemically induced burst. The converse is also true, suggesting that heterologous desensitization of the oxidative burst does not extend to mixed chemical and mechanical/osmotic stimuli. However, communication between these disparate forms of elicitation is still demonstrated to occur, since low-level chemical stimuli strongly synergize concurrent low-level osmotic stimuli and vice versa. Furthermore, the pattern of synergy changes dramatically if one stimulus is administered immediately prior to the other. Taken together, these data demonstrate that significant cross-talk occurs among the different signaling pathways of the oxidative burst and that the overall process is tightly regulated.

Bacterial Outer Membrane Proteins↗
PubMed2000

Application of in vivo and ex vivo magnetic resonance imaging for evaluation of tranilast on neointima formation following balloon angioplasty of the rat carotid artery.

OBJECTIVE: Recent studies suggest that tranilast inhibits a variety of agents implicated in neointimal growth and restenosis in experimental animal models and humans. We report here a study evaluating the efficacy of tranilast in the rat carotid artery balloon angioplasty model, a model that mimics many aspects of the percutaneous transluminal angioplasty procedure in humans. Efficacy was determined based on in vivo and ex vivo magnetic resonance imaging (MRI) as well as by histomorphometry. The utility of this study, using a reverse paradigm, is to investigate if agents successful in the clinic can demonstrate efficacy in this animal model primary screen as measured by MRI and histomorphometry. METHODS: Tranilast (300 mg/kg/day, p.o.) was administered to Sprague-Dawley rats 3 days prior to balloon injury and continued for 14 days after injury. Three methods of measuring the vascular injury that occurs in this model were employed: (1) in vivo MRI, used to measure in vivo lumen volumes for the carotid artery once at baseline (pre-surgery) and again at 14 days post angioplasty; (2) ex vivo MRI (and histomorphometry), used to evaluate the total arterial wall thickness and the intima-to-media ratio; and (3) analysis of collagen density, used to evaluate the efficacy of tranilast to abrogate collagen synthesis and deposition following vascular injury. RESULTS: Tranilast provided 33% protection (P<0.05) from angioplasty-induced lumen narrowing as measured by MRI in vivo. The results of the ex vivo MR analysis of total wall thickness showed a 14% protection of angioplasty-induced narrowing (P<0.05), and the mean intima-to-media ratio showed a 39% (P<0.006) protection for the tranilast-treated rats. Histological analysis of the mean intima-to-media ratio demonstrated that tranilast provided 36% (P<0. 01) protection in the intima-to-media ratio. Further, treatment with tranilast showed a 52% reduction in collagen density of the intimal layer and a 70% reduction in collagen density of the medial layer of the injured arteries. CONCLUSION: The data obtained by in vivo MRI, ex vivo MRI, histology and collagen analysis demonstrate that tranilast provided significant beneficial effects in inhibiting neointimal formation in the rat carotid artery model. Also this study, to the best of our knowledge, is the first to harness complimentary information from various technologies, including lumen patency by in vivo MRI, neointimal formation by ex vivo MRI and conventional histomorphometry, and histological analysis for collagen density, to provide a comprehensive understanding of the pathology in this disease model.

Analysis of Variance↗
PubMed2000

Acardiac twin pregnancy with neonatal resolution of donor twin cardiomyopathy.

BACKGROUND: Twin reverse arterial perfusion, as with acardiac fetuses, is a rare complication of multifetal pregnancy. Prognosis of the donor twin is guarded because of the high risk of cardiac failure, polyhydramnios, and preterm delivery. CASE: A 40-year-old woman, gravida 4, para 3, was diagnosed at 19 weeks' gestation with a twin pregnancy complicated by an acardiac, acephalic fetus. Serial amniocenteses were done to decompress the hydramnios between 27 and 33 weeks. Ultrasonography showed ventricular septal hypertrophy in the donor twin at 27 weeks, and cesarean delivery was done at 33 weeks. The neonatal course was complicated by hypertrophic cardiomyopathy, which resolved without sequelae by 1 year of age. CONCLUSION: Antenatal sonographic monitoring of interventricular septal thickness can be a useful marker to predict neonatal cardiac sequelae.

Adult↗
PubMed2000

Volatile organic compound concentrations and emission rates in new manufactured and site-built houses.

Concentrations of 54 volatile organic compounds (VOCs) and ventilation rates were measured in four new manufactured houses over 2-9.5 months following installation and in seven new site-built houses 1-2 months after completion. The houses were in four projects located in hot-humid and mixed-humid climates. They were finished and operational, but unoccupied. Ventilation rates ranged from 0.14-0.78 h-1. Several of the site-built houses had ventilation rates below the ASHRAE recommended value. In both manufactured and site-built houses, the predominant airborne compounds were alpha-pinene, formaldehyde, hexanal, and acetic acid. Formaldehyde concentrations were below or near 50 ppb with a geometric mean value for all houses of 40 ppb. Similarities in the types of VOCs and in VOC concentrations indicated that indoor air quality in the houses was impacted by the same or similar sources. Major identified sources included plywood flooring, latex paint and sheet vinyl flooring. One site-built house was operated at ventilation rates of 0.14 and 0.32 h-1. VOC emission rates calculated at the two conditions agreed within +/- 10% for the most volatile compounds. Generally, the ratios of emission rates at the low and high ventilation rates decreased with decreasing compound volatility. Changes in VOC emission rates in the manufactured houses over 2-9.5 months after installation varied by compound. Only several compounds showed a consistent decrease in emission rate over this period.

Air Pollution, Indoor↗
PubMed2000

A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor.

The amyloid beta-protein precursor gives rise to the amyloid beta-protein, the principal constituent of senile plaques and a cytotoxic fragment involved in the pathogenesis of Alzheimer disease. Here we show that amyloid beta-protein precursor was proteolytically cleaved by caspases in the C terminus to generate a second unrelated peptide, called C31. The resultant C31 peptide was a potent inducer of apoptosis. Both caspase-cleaved amyloid beta-protein precursor and activated caspase-9 were present in brains of Alzheimer disease patients but not in control brains. These findings indicate the possibility that caspase cleavage of amyloid beta-protein precursor with the generation of C31 may be involved in the neuronal death associated with Alzheimer disease.

Alzheimer Disease↗