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Biomedical subjects

U Das

Publications and source records attributed to U Das.

At least 19 recordsLinked to original sources
PubMed2004

Antimycobacterial arylidenecyclohexanones and related Mannich bases.

Several series of 2-arylidenecyclohexanones and related Mannich bases as well as various 2,6-bis(arylidene)cyclohexanones were evaluated against Mycobacterium tuberculosis H37Rv. Using a concentration of 12.5 microg/ml, nearly half of the unsaturated ketones inhibited the growth of the microorganism by 21-66% while all of the Mannich bases achieved 99% or greater inhibition. The relative hydrophobicities and widths of the molecules may have been contributing factors as to whether bioactivity was present or absent. Two of the Mannich bases demonstrated noteworthy potencies towards Mycobacterium avium. The conclusion was drawn that Mannich bases of 2-arylidenecyclohexanones represent a novel class of antimycobacterials.

Animals↗
PubMed2004

Cytotoxic and topographical properties of 6-arylidene-2-dimethylaminomethylcyclohexanone hydrochlorides and related compounds.

A number of 2-arylidenecyclohexanones (1a-h) were converted into the corresponding Mannich bases (2a-h) and (3a,f). Evaluation against murine L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes revealed the marked cytotoxicity of the Mannich bases and also the fact that almost invariably these compounds were more potent than the precursor enones (1a-h). Further evaluation of most of the Mannich bases towards a panel of nearly 60 human tumour cell lines confirmed their utility as potent cytotoxins. In this assay, the compounds showed growth-inhibiting properties greater than the anticancer alkylator melphalan. QSAR studies revealed that in some cell lines compounds possessing small electron-attracting aryl substituents showed the greatest potencies. Molecular modeling and X-ray crystallography demonstrated that various interatomic distances and torsion angles correlated with cytotoxicity. A representative compound (2a) demonstrated weak inhibiting properties towards human N-myristoyltransferase and stimulated a tyrosine protein kinase. A single dose of 100 mg/kg of most of the compounds did not prove to be lethal in mice.

Acyltransferases↗
PubMed2004

Anticonvulsants containing the N-(3-aryl-2-propenoyl) amido pharmacophore.

A series of 1-(3-aryl-2-propenoyl)-4-oxopiperidines (1) as well as some related semicarbazones (2) and thiosemicarbazones (3) were prepared in order to determine whether the relative locations of aryl rings and amidic groups would lead to novel anticonvulsant agents. Initially the compounds were administered intraperitoneally to mice and examined in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and neurotoxicity (NT) screens. The biodata revealed that anticonvulsant properties were displayed by most of the compounds in series (1), in half of the semicarbazones (2) while protection was absent by members of series (3). Molecular modeling was utilized in order to compare the positions of a phenyl ring in relation to amidic groups in representative compounds in series (1-3) with previously reported anticonvulsant agents. Molecular simplification of 4-oxo-1-(3-phenyl-2-propenoyl)piperidine (la) led to 1-(3-phenyl-2-propenoyl)piperidine (7) and N,N-diethylcinnamamide (8) with retention of anticonvulsant properties. Both (la) and (8) afforded protection in the hippocampal kindling screen in rats. When administered orally to rats, (la) and (8) demonstrated activity in the MES screen and in the case of (8), a huge protection index was observed revealing it to be an important lead compound. The IC50 values of all of the compounds towards murine P388 cells were in excess of 50 microM while several compounds displayed cytotoxicity towards Mycobacterium tuberculosis.

Amides↗
PubMed2003

Cytotoxic mannich bases of 1-arylidene-2-tetralones.

Various 1-arylidene-2-tetralones 1 had been shown previously to possess moderate cytotoxic properties unaccompanied by murine toxicity. The objective of the present investigation was to undertake different molecular modifications of representative members of series 1 with a view to discerning those structural features leading to increased potencies. All compounds were evaluated using human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. The Mannich bases 2, 4, 5 and 7 possessed increased potencies compared to the corresponding unsaturated ketones 1 and in general were potent cytotoxics having IC50 values in the 0.2-10 microM range. QSAR using the cytotoxicity data for 2a-e suggested that potency was positively correlated with the size of the substituents in the arylidene aryl ring. Compounds 2a-f were evaluated using a panel of approximately 53 human tumour cell lines and, when all cell lines were considered, were more potent than the reference drug melphalan. In particular, marked antileukemic activity was displayed. Molecular modeling was utilized in order to evaluate whether the shapes of the different compounds contributed to the varying potencies observed. Representative compounds demonstrated minimal or no inhibiting properties towards human N-myristoyltransferase (NMT) and did not bind to calf thymus DNA. This study has revealed a number of unique lead molecules as candidate anti-neoplastic agents serving as prototypes for future development.

Acyltransferases↗
PubMed2003

IGF-I and IGF-binding protein-3 measurements on filter paper blood spots in children and adolescents on GH treatment: use in monitoring and as markers of growth performance.

BACKGROUND/AIM: In childhood an appropriate response to GH treatment is achieved by titration of growth response against dose administered, with careful observation for side-effects. In order to evaluate the potential use of IGF monitoring in children treated with GH, a cross-sectional study has been carried in 215 children and adolescents (134 with GH deficiency (GHD), 54 with Turner syndrome (TS) and 27 with non-GHD growth disorders) treated with GH for 0.2-13.7 years. METHODS: IGF-I and IGF-binding protein-3 (IGFBP-3) were measured in ELISAs, using dried capillary blood collected onto filter papers. Results were expressed as the mean S.D. range (SDS). Values of either analyte < -2 or > +2 SDS were considered abnormal. RESULTS: IGF-I and IGFBP-3 SDS were higher in the TS and non-GHD groups (mean +0.01 and +0.1 respectively) than in those with GHD (mean value -0.6). Nineteen per cent of the IGF-I values (13% low, 6% high) and 12% of IGFBP-3 values were abnormal (10% low, 2% high). Abnormalities, either low or high, were most common in the GHD group. There was a weak but significant relationship between change in height SDS over the Year up to the time of sampling in the whole group and IGF-I SDS. Satisfactory growth performance (+0.5>change in height SDS> -0.5) was found in those with high (7.2%), normal (60%) and low (9.3%) IGF-I levels. Overall, it was estimated that 26% of the tests would indicate that an adjustment to GH dose (up in 18% and down in 8%) could be considered. CONCLUSIONS: From this cross-sectional study of IGF monitoring across a broad range of diagnoses and ages, it can be concluded that the majority of children on GH have normal levels of IGF-I and IGFBP-3, but 26% of tests could suggest that a change of GH dose should be considered. Regular monitoring of IGF-I and IGFBP-3 should be considered in any child on GH treatment.

Adolescent↗
PubMed2001

Checking nucleic acid crystal structures.

The program SFCHECK [Vaguine et al. (1999), Acta Cryst. D55, 191-205] is used to survey the quality of the structure-factor data and the agreement of those data with the atomic coordinates in 105 nucleic acid crystal structures for which structure-factor amplitudes have been deposited in the Nucleic Acid Database [NDB; Berman et al. (1992), Biophys. J. 63, 751-759]. Nucleic acid structures present a particular challenge for structure-quality evaluations. The majority of these structures, and DNA molecules in particular, have been solved by molecular replacement of the double-helical motif, whose high degree of symmetry can lead to problems in positioning the molecule in the unit cell. In this paper, the overall quality of each structure was evaluated using parameters such as the R factor, the correlation coefficient and various atomic error estimates. In addition, each structure is characterized by the average values of several local quality indicators, which include the atomic displacement, the density correlation, the B factor and the density index. The latter parameter measures the relative electron-density level at the atomic position. In order to assess the quality of the model in specific regions, the same local quality indicators are also surveyed for individual groups of atoms in each structure. Several of the global quality indicators are found to vary linearly with resolution and less than a dozen structures are found to exhibit values significantly different from the mean for these indicators, showing that the quality of the nucleic acid structures tends to be rather uniform. Analysis of the mutual dependence of the values of different local quality indicators, computed for individual residues and atom groups, reveals that these indicators essentially complement each other and are not redundant with the B factor. Using several of these indicators, it was found that the atomic coordinates of the nucleic acid bases tend to be better defined than those of the backbone. One of the local indicators, the density index, is particularly useful in spotting regions of the model that fit poorly in the electron density. Using this parameter, the quality of crystallographic water positions in the analyzed structures was surveyed and it was found that a sizable fraction of these positions have poorly defined electron density and may therefore not be reliable. The possibility that cases of poorly positioned water molecules are symptomatic of more widespread problems with the structure as a whole is also raised.

Carbohydrates↗
PubMed2001

Molecular and structural analysis of two novel StAR mutations in patients with lipoid congenital adrenal hyperplasia.

Mutations in the gene encoding steroidogenic acute regulatory protein (StAR) cause lipoid congenital adrenal hyperplasia. We report a novel homozygous splice site mutation (IVS1 + 2T --> G) in STAR in two sisters (46XY, 46XX) who presented with primary adrenal insufficiency at birth and a novel homozygous R182H missense mutation in the putative lipid transfer domain of StAR in a phenotypic female (46XY) with adrenal failure and a parotid tumor. These cases highlight the importance of StAR-dependent steroidogenesis during fetal development and early infancy and of the critical functional role of R182 in cholesterol transport.

Adrenal Hyperplasia, Congenital↗
PubMed2000

Occurrence of Salmonella typhi infection in Rourkela, Orissa.

Between January 1996 and December 1998, the isolation rate of Salmonella typhi in Rourkela was found to be on a steady rise. Of the 7866 samples (blood and bone marrow) tested, 988 were found positive for S. typhi giving an overall per cent positivity of 12.56. Enteric fever was found to occur almost throughout the year with a peak from early winter up to the end of summer. In this study, chloramphenicol was found to have an average sensitivity of 87.46 per cent. Ceftriaxone showed 100 per cent sensitivity.

Adult↗
PubMed2000

Multidrug resistant Salmonella typhi in Rourkela, Orissa.

Out of 5410 blood samples 715 samples were found positive for Salmonella typhi. Enteric fever was prevalent for last three years in Rourkela. In last two years, a number of multidrug resistant strains of Salmonella typhi was isolated which constituted almost 16.1% of the total isolates. In this study, chloramphenicol sensitivity was found quite high (86.5%) and ceftriaxone showed 100% sensitivity. Resistance to ciprofloxacin was found 2.5% which due to direct consequence of indiscriminate use of antibiotics, either singly or in combination.

Anti-Bacterial Agents↗
PubMed1999

HCV seroreactivity and detection of HCV RNA in cirrhotics.

This study was carried out to determine the presence of HCV infection in cirrhotic patients and to compare their serologic profiles with detection of HCV RNA by RT-PCR. Liver function profiles were assessed and correlated with infection. Coinfection of HCV with HBV was studied in the Indian context Sera from 62 patients of biopsy confirmed cirrhosis and an equal number of asymptomatic controls were tested for HCV by two ELISA (third generation) kits and nested reverse transcription PCR using primers from the 5'NCR. Other tests included HBV serology (ELISA for HBsAg and anti-HBc) and liver function tests. Twenty-four (38.7%) cases were HCV infected, of which 17 (70.8%) had past exposure to HBV or were coinfected with HBV (either being chronically infected or carriers of HBV). There was no significant difference in the clinical and liver function profiles of HCV infected and uninfected cirrhotics. Similarly, no difference was observed in cases coinfected with both HCV and HBV compared with those infected with HCV alone. Although the difference between positivity of HCV RNA and of anti-HCV was not significant, HCV RNA and anti HCV were present together in only 7/62 (11.3%) cases. Thus testing for both antibody and HCV RNA would be more appropriate than either test alone. HBV infection was seen in about one-fourth of HCV infected cirrhotics. About one-fourth (25.8%) patients had non-B, non-C cirrhosis in whom testing for HCV variants and other recently characterized hepatitis viruses could be performed.

Adult↗
PubMed1997

Studies on the aerobic photooxidation of cysteine using riboflavin as a sensitizer: evidence for the photogeneration of a superoxide anion and hydrogen peroxide.

The riboflavin sensitized oxidation of cysteine under an aerobic condition was investigated. The effects of various scavengers, such as superoxide dismutase, catalase, mannitol, sodium azide and potassium ferrocyanide (an electron donor), on the photooxidation were determined. A reaction mechanism involving the superoxide anion is proposed for the photooxidation of cysteine to cysteic acid.

Cysteine↗
PubMed1997

ERCP in situs inversus: do we need to turn the other way?

Endoscopic procedures are difficult in patients with situs inversus owing to left-right reversal of viscera. Conventionally, reversal of the position of the endoscopist in relation to the patient is advocated to overcome the anatomical difficulty. We describe a patient with chronic calcific pancreatitis and pseudocyst of the pancreas who had situs inversus. ERCP was performed with minor modification of maneuvers with the patient in the usual left lateral decubitus and the endoscopist on the left of the table.

Adult↗