Detection of a rare splice acceptor site mutation (IVS I nt 130 G-->C) of the beta globin gene in 3 patients of Eastern India.
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Child↗
Biomedical subjects
S Chandra
Publications and source records attributed to S Chandra.
Variable severity of beta-thalassemia patients of eastern India: effect of alpha-thalassemia and xmnI polymorphism.
Sixty-four thalassemia and E-beta thalassemia patients were studied for factors that modulate the severity of the disease; i.e., mutation of beta-globin gene, presence of alpha-deletion, and presence of an XmnI site at the -158 position of the Gy gene. Presence of alpha-deletion and/or homozygosity for the XmnI site was in general associated with less-severe disease. About 12% of the patients harbored single alpha-gene deletion, and the gene frequency of the XmnI polymophism in these patients is 0.48.
Deoxyribonucleases, Type II Site-Specific↗
Eprosartan reduces cardiac hypertrophy, protects heart and kidney, and prevents early mortality in severely hypertensive stroke-prone rats.
OBJECTIVE: Eprosartan is a selective angiotensin II type I receptor antagonist approved for the treatment of hypertension. In the present studies, eprosartan's ability to provide end-organ protection was evaluated in a model of cardiomyopathy and renal failure in stroke-prone rats (SP). METHODS: SP were fed a high fat (24.5% in food) and high salt (1% in water) diet (SFD). Eprosartan (60 mg/kg/day) or vehicle (saline control) (n = 25/group) was administered by intraperitoneally-implanted minipumps to these SP on the SFD for 12 weeks. Normal diet fed SP and WKY rats (n = 25/group) were also included for comparison (i.e. served as normal controls). Mortality, hemodynamics, and both renal and cardiac function and histopathology were monitored in all treatment groups. RESULTS: Eprosartan decreased the severely elevated arterial pressure (-12%; P < 0.05) produced by SFD but did not affect heart rate. Vehicle-treated SP-SFD control rats exhibited significant weight loss (-13%; P < 0.05) and marked mortality (50% by week 6 and 95% by week 9; P < 0.01). Eprosartan-treated SP-SFD rats maintained normal weight, and exhibited zero mortality at week 12 and beyond. Eprosartan prevented the increased urinary protein excretion (P < 0.05) that was observed in vehicle-treated SP-SFD rats. Echocardiographic (i.e. 2-D guided M-mode) evaluation indicated that SP-SFD vehicle control rats exhibited increased septal (+22.2%) and posterior left ventricular wall (+30.0%) thickness, and decreased left ventricular chamber diameter (-15.9%), chamber volume (-32.7%), stroke volume (-48.7%) and ejection fraction (-22.3%), and a remarkable decrease in cardiac output (-59.3%) compared to controls (all P < 0.05). These same parameters in eprosartan-treated SP-SFD rats were normal and differed markedly and consistently from vehicle-treated SP-SFD rats (i.e. treatment prevented pathology; all P < 0.05). Cardiac-gated MRI data confirmed the ability of eprosartan to prevent cardiac pathology/remodeling (P < 0.05). Histopathological analysis of hearts and kidneys indicated that eprosartan treatment significantly reduced end-organ damage (P < 0.01) and provided corroborative evidence that eprosartan reduced remodeling of these organs. Vehicle-treated SP-SFD rats exhibited a 40% increase in the plasma level of pro-atrial natiuretic factor that was reduced to normal by eprosartan (P < 0.05). CONCLUSION: These data demonstrate that eprosartan, at a clinically relevant dose, provides significant end-organ protection in the severely hypertensive stroke-prone rat. It preserves cardiac and renal structural integrity, reduces cardiac hypertrophy and indices of heart failure, maintains normal function of the heart and kidneys, and eliminates premature mortality due to hypertension-induced end-organ failure.
Acrylates↗
Transvaginal ultrasound and digital examination in predicting successful labor induction.
OBJECTIVE: To compare transvaginal ultrasound and digital cervical examination in predicting successful induction in post-term pregnancy. METHODS: Transvaginal ultrasound and digital vaginal examinations were performed on 122 women at 41 or more weeks' gestation, immediately before labor induction. Ultrasound assessments of cervical length, dilatation, and presence of funneling were compared with the components of the Bishop score. The primary outcome was the rate of vaginal delivery. Secondary outcomes assessed included the rates of active labor in 12 hours, vaginal delivery in 12 and 24 hours, mean duration of latent phase, and induction to vaginal delivery interval. Linear and multiple logistic regression models were generated to identify factors independently associated with successful induction. RESULTS: No ultrasound characteristic predicted primary or secondary outcomes. Bishop score (odds ratio [OR] 2.98, 95% confidence interval [CI] 1.71, 5.20), cervical position (OR 4.35, 95% CI 1.41, 12.50), and maternal age (OR 1.15, 95% CI 1.01, 1.30) independently predicted vaginal delivery. Maternal weight (OR 0.96, 95% CI 0.94, 0.98), cervical dilatation (OR 6.08, 95% CI 1.70, 21.68), and effacement (OR 2.34, 95% CI 1.16, 4.73) independently predicted active labor in 12 hours. Independent predictors of vaginal delivery in 12 hours were induction method (P <.001), cervical dilatation (OR 11.16, 95% CI 3.17, 39.29), gravidity (OR 2.06, 95% CI 1.13, 3.77), and maternal weight (OR 0.96, 95% CI 0.93, 0.99). Cervical effacement (OR 2.70, 95% CI 1.59, 4.57) and parity (OR 7.10, 95% CI 2.22, 22.72) independently predicted vaginal delivery in 24 hours. Maternal weight, cervical position, and cervical dilatation were independently associated with latent phase labor duration. Factors independently associated with length of induction to delivery interval were parity, cervical effacement, and maternal weight. CONCLUSION: Transvaginal ultrasound does not predict successful labor induction in post-term pregnancy as well as digital cervical examination.
Adult↗
Anti-inflammatory activity of Dalbergia sissoo leaves.
The possible anti-inflammatory activity of the 90% ethanolic extract of Dalbergia sissoo leaves (DSELE) was studied in different models of inflammation in rats after oral administration at doses of 100, 300 and 1000 mg/kg. DSELE significantly inhibited carrageenin, kaolin and nystatin-induced paw oedema, as well as the weight of granuloma induced by a cotton pellet. It also inhibited dye leakage in acetic acid-induced vascular permeability test in mice. DSELE was devoid of ulcerogenic effect on the gastric mucosa of rats in acute and chronic tests. In acute toxicity studies, it was found to be safe up to 10.125 g/kg, p.o. in the rat. It was concluded that the D. sissoo leaf extract possessed significant anti-inflammatory activity (in acute, sub-acute and chronic models of inflammation) without any side effect on gastric mucosa.
Animals↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Subcellular imaging by dynamic SIMS ion microscopy.
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Animals↗
Invasive aspergillosis presenting as a cavernous sinus mass in immuno competent individuals; report of 3 cases.
Aspergillosis of the cavernous sinus is rare, especially in immuno competent individuals. We report three such cases secondary to paranasal sinus aspergillosis, with imaging findings.
Adult↗