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Biomedical subjects

S Chandrasekaran

Publications and source records attributed to S Chandrasekaran.

At least 19 recordsLinked to original sources
PubMed2006

Refractive change in thyroid eye disease (a neglected clinical sign).

BACKGROUND/AIMS: The literature on refractive change in thyroid eye disease (TED) is limited. This study documents the refractive change in patients with TED undergoing orbital decompression. The authors propose possible mechanisms for their acquired refractive error. METHODS: This is a retrospective observational case study of five patients with progressive TED. Their detailed eye examinations including refractive state preoperatively and postoperatively are presented. RESULTS: An acquired hypermetropic shift with active TED before orbital decompression of up to 3.75 D spherical equivalent refraction (SER) is reported in one patient. Post-orbital decompression, an induced myopic shift of between 1.00-2.50 D SER for all patients is observed, noted to range from 1 day following surgery to up to 9 months, dependent on the availability of data. Axial length increased in two cases corresponding to postoperative myopic shift. Magnetic resonance imaging findings of one patient demonstrate flattening of the posterior pole as a cause of the acquired preoperative hypermetropia. CONCLUSIONS: TED has a significant effect on the refractive state of patients. The proposed mechanism of acquired hypermetropia relates to increased volume of orbital contents with flattening of the posterior globe. This is reversed with successful orbital decompression. Documentation of refractive error in all cases of progressive TED is recommended. Progressive acquired hypermetropia may be suggestive of TED activity.

Adult↗
PubMed2005

But-2-ynylbisoxycarbonyl chloride: a novel C2-symmetric reagent for the protection of amines and amino acids.

[reaction: see text] A novel C2-symmetric protecting group for amines, the but-2-ynylbisoxycarbonyl (Bbc) group, is developed, which can be deblocked with tetrathiomolybdate under neutral conditions. One equivalent of the bischloroformate, BbcCl, is used for the protection of 2 equiv of the amine. Its application in peptide synthesis is established through the synthesis of a tripeptide, and its orthogonality with Cbz, Fmoc, and Boc groups has been studied.

Journal Article↗
PubMed2005

Mechanistic studies on percutaneous penetration enhancement by N-(4-halobenzoyl)-S,S-dimethyliminosulfuranes.

Halogen-substituted iminosulfuranes are transdermal penetration enhancers (TPEs) in permeation studies using hairless mouse or human cadaver skin. The interaction of N--(4--R-benzoyl)-S,S-dimethyliminosulfuranes 1--4, where R=H, Cl, Br, and I, with l-alpha-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) has been studied using differential scanning calorimetry, isothermal titration calorimetry, nuclear Overhauser effect spectroscopy (NOESY), and NMR spectroscopy, and by calculation of the iminosulfurane polarizabilities in order to elucidate the molecular basis of the TPE activity. The active compounds reduce the melting temperature of the gel-to-liquid-crystal phase transition and induce multiple components in the transition excess heat capacity profile. The partitioning of the bromo derivative 3, the most active compound, into DMPC is unique in that 3 may be trapped in the bilayer, affording an enhanced residence time and a reason for its high TPE activity. The entropy decrease associated with the transfer of 3 to the bilayer is much lower than that for the other compounds, indicating that 3 occupies or induces sites that afford it considerable local motional freedom. Correlations between the iminosulfurane TPE activities, the partition coefficients, and NOESY crosspeak volume were observed. Molecular polarizabilities are not consistent with a TPE mode of action involving interaction of these agents with protein side chains.

Animals↗
PubMed2005

Rice husk filtrate as a nutrient medium for the growth of Desulfotomaculum nigrificans: characterisation and sulfate reduction studies.

The filtrate obtained by interacting a known amount of rice husk with deionised, Milli-Q water was assessed as a carbon source and nutrient medium for the growth of Desulfotomaculum nigrificans, a typical sulfate-reducing bacterium. The filtrate contained essential growth constituents such as magnesium, potassium, phosphorous apart from calcium, sodium, chloride and sulfate ions. Based on the 1H and 13C NMR characterization studies, the organic composition of the components dissolved from the rice husk, was found to be: (i) 66% lignocellulosic material, (ii) 24% xylose+arabinose and (iii) 10% galactose. The growth studies indicated a 15-fold increase in the bacterial cell number in about 20 days. Nearly 81% and 66% reduction in sulfate concentration could be achieved in about 28 days, from the solutions containing initial sulfate concentrations of 550 mg/l and 1200 mg/l respectively. In both the cases studied, the iron concentration could be reduced by over 85%.

Carbohydrate Metabolism↗
PubMed2005

Microwave-assisted synthesis and anti-bacterial activity of some 2-amino-6-aryl-4-(2-thienyl)pyrimidines.

Some novel 2-amino-6-aryl-4-(2-thienyl)pyrimidines were synthesized from 3-aryl-1-thien-2-ylprop-2-en-1-ones and guanidine hydrochloride in presence of alkali by conventional heating in alcoholic medium and microwave heating in solvent-free conditions. The compounds were evaluated for in vitro anti-bacterial activity. The anti-bacterial data revealed that compounds 5a-e had better activity against tested gram-positive organisms than the reference ciprofloxacin and norfloxacin. However, the compounds were nearly inactive against gram-negative bacteria. Compounds 5c and e were the most active compounds against gram-positive bacteria.

Anti-Bacterial Agents↗
PubMed2003

Efficient syntheses of benzothiazepines as antagonists for the mitochondrial sodium-calcium exchanger: potential therapeutics for type II diabetes.

Type II diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular, renal, neurologic, and retinal complications. While several drugs are currently prescribed to treat type II diabetes, their efficacy is limited by mechanism-related side effects (weight gain, hypoglycemia, gastrointestinal distress), inadequate efficacy for use as monotherapy, and the development of tolerance to the agents. Consequently, combination therapies are frequently employed to effectively regulate blood glucose levels. We have focused on the mitochondrial sodium-calcium exchanger (mNCE) as a novel target for diabetes drug discovery. We have proposed that inhibition of the mNCE can be used to regulate calcium flux across the mitochondrial membrane, thereby enhancing mitochondrial oxidative metabolism, which in turn enhances glucose-stimulated insulin secretion (GSIS) in the pancreatic beta-cell. In this paper, we report the facile synthesis of benzothiazepines and derivatives by S-alkylation using 2-aminobenzhydrols. The syntheses of other bicyclic analogues based on benzothiazepine, benzothiazecine, benzodiazecine, and benzodiazepine templates are also described. These compounds have been evaluated for their inhibition of mNCE activity, and the results from the structure-activity relationship (SAR) studies are discussed.

Animals↗
PubMed2002

Propargyloxycarbonyl (Poc) as a protective group for the hydroxyl function in carbohydrate synthesis.

[reaction: see text] The propargyloxycarbonyl (Poc) group can be used for the selective protection of the hydroxyl function in carbohydrates and can be removed under neutral conditions using tetrathiomolybdate MoS(4)(2-) (1) in CH(3)CN at room temperature. Under the conditions of deprotection benzylidine acetals, benzyl ethers, acetyl and levulinoyl esters, and allyl and benzyl carbonates are left untouched. It has also been shown that the new protective group (Poc) is compatible with acidic, basic, and also glycosylation conditions.

Journal Article↗
PubMed2002

Phenolic antibacterials from Piper betle in the prevention of halitosis.

Piper betle L. (Piperaceae) leaves which are traditionally used in India and China in the prevention of oral malodor was examined by bioassay-guided fractionation to yield allylpyrocatechol (APC) as the major active principle which showed promising activity against obligate oral anaerobes responsible for halitosis. The biological studies with APC indicated that the potential to reduce methylmercaptan and hydrogen sulfide was mainly due to the anti-microbial activity as established using dynamic in vitro models.

Anti-Bacterial Agents↗
PubMed2000

Relative prevalence of hepatitis B viral markers and hepatitis C virus antibodies (anti HCV) in Madurai, south India.

(1) The positivity of HBsAg was 4% (75/1819) whereas anti HCV was present only in 0.75% (27/3574) of blood donors. (2) 5.3% (4/75) of hospital staff had HBsAg alone in their blood samples. One doctor, one Staff nurse, one Lascar and one Sanitary worker were positive for HBsAg. None of them were positive for anti HBcIgm and anti-HCV. (3) 29% (31/115) of suspected hepatitis cases were positive for any one of the viral markers or both. 21% (15/72) of males and 14% (6/43) of females were positive for HBsAg. Whereas only 4% (3/72) of males and 2% (1/43) of females were positive for anti HCW. Both HBsAg and anti HCV were found in 8% (6/72) of males only. The age group predominantly, i.e. in 29 out of 31 cases found positive for HBsAg and/or anti HCV, was above 15 years. Two remaining HBsAg positive cases belonged to the 5 to 14 years age group. 71% (84/115) of suspected hepatitis cases were negative for both HBsAg and anti HCV.

Biomarkers↗
PubMed1999

Catalytic Aerobic Oxidation of Cycloalkanes with Nanostructured Amorphous Metals and Alloys.

Under mild conditions (40 atm O(2), 28 degrees C, 10-15 h), an efficient aerobic oxidation of cycloalkanes to cycloalkanols can be achieved using nanostructured amorphous metals such as Fe and Co and an amorphous alloy like Fe(20)Ni(80) as catalysts. For example, cyclohexane is oxidized to cyclohexanol with 32-41 % conversion, while 1-adamantanol is formed from adamantane with 52-57 % conversion.

Journal Article↗
PubMed1999

Relation between infarct artery patency at late angiography after acute myocardial infarction and signal-averaged electrocardiography.

The angiograms of 89 patients were reviewed from the LATE Ancillary Study (randomized trial of recombinant tissue plasminogen activator vs placebo in patients with symptom onset after 6 hours of myocardial infarction) to determine patency of the infarct-related artery (IRA). In the occluded IRA group (n = 35), the incidence of signal-averaged electrocardiographic abnormality (fQRS > 120 ms) was significantly higher (p = 0.04), the filtered QRS duration was significantly longer (p = 0.007), and the V40 was significantly shorter (p = 0.02), compared with the patent IRA group (n = 54).

Adult↗
PubMed1999

Pro-adhesive and chemotactic activities of thrombospondin-1 for breast carcinoma cells are mediated by alpha3beta1 integrin and regulated by insulin-like growth factor-1 and CD98.

Thrombospondin-1 (TSP1) is a matricellular protein that displays both pro- and anti-adhesive activities. Binding to sulfated glycoconjugates mediates most high affinity binding of soluble TSP1 to MDA-MB-435 cells, but attachment and spreading of these cells on immobilized TSP1 is primarily beta1 integrin-dependent. The integrin alpha3beta1 is the major mediator of breast carcinoma cell adhesion and chemotaxis to TSP1. This integrin is partially active in MDA-MB-435 cells but is mostly inactive in MDA-MB-231 and MCF-7 cells, which require beta1 integrin activation to induce spreading on TSP1. Integrin-mediated cell spreading on TSP1 is accompanied by extension of filopodia containing beta1 integrins. TSP1 binding activity of the alpha3beta1 integrin is not stimulated by CD47-binding peptides from TSP1 or by protein kinase C activation, which activate alphavbeta3 integrin function in the same cells. In MDA-MB-231 but not MDA-MB-435 cells, this integrin is activated by pertussis toxin, whereas serum, insulin, insulin-like growth factor-1, and ligation of CD98 increase activity of this integrin in both cell lines. Serum stimulation is accompanied by increased surface expression of CD98, whereas insulin-like growth factor-1 does not increase CD98 expression. Thus, the pro-adhesive activity of TSP1 for breast carcinoma cells is controlled by several signals that regulate activity of the alpha3beta1 integrin.

Antigens, CD↗
PubMed1999

Efficacy of bretylium tosylate for ventricular tachycardia.

In 20 patients with inducible ventricular tachycardia (VT), intravenous bretylium tosylate infused as a 10-mg/kg bolus followed by 2 mg/min caused no change in refractory periods and did not suppress inducibility of VT. The use of bretylium for the treatment of VT should be reexamined.

Anti-Arrhythmia Agents↗
PubMed1998

Transfer and expression of a multiple antibiotic resistance plasmid in marine bacteria.

Conjugal transfer of a multiresistance plasmid from Pseudomonas fluorescens to halophilic and halotolerant bacteria was studied under in vitro and in situ conditions. Mating conducted in broth as well as on plates yielded a plasmid transfer frequency of as high as 10(-3). Among these two, plate mating facilitated conjugal transfer of plasmid, because the cell-to-cell contact is more in plate mating. When P. fluorescens was incubated in seawater, the organism progressively lost its colony forming activity within 15 days. Microscopic examination revealed the presence of very short rods, indicating that the cells have become viable but nonculturable (VNC). Mating conducted in natural seawater without any added nutrients revealed that the conjugal transfer is influenced by the physical state of the donor and the recipients as well as the availability of nutrients. But a plasmid transfer frequency of 10(-7) was obtained even after the donor cells have become VNC suggesting that the nonculturable state and nutrient deprived condition may not limit plasmid transfer. The results suggest that the terrestrial bacteria entering into the seawaters with antibiotic resistance plasmids may be responsible for the prevalence of resistance genes in the marine environment.

Anti-Bacterial Agents↗
PubMed1998

Plasmid-mediated rifampicin resistance in Pseudomonas fluorescens.

Rifampicin is an antibiotic mostly used to treat tuberculosis and leprosy, and, occasionally, other diseases. Resistance is due to alterations in membrane permeability or to mutation in the rpoB gene coding for mRNA polymerase. Both these mechanisms originate via chromosomal mutation. However, a rifampicin-resistant Pseudomonas fluorescens strain harboured a multiresistance plasmid which transferred rifampicin resistance when transformed into P. putida or Escherichia coli. Rifampicin readily diffused into the sensitive cells of the E. coli and P. putida recipients, but the transformants with the plasmid, pSCL were resistant to the drug and did not accumulate it. Potassium cyanide restored the diffusion of rifampicin into the resistant cells, indicating that an efflux pump was involved in the resistance mechanism. The resistance of the transformants and the wild strain was also abolished in sphaeroplasts generated by EDTA lysozyme treatment. Analysis of membrane proteins by SDS-PAGE revealed the presence of two new proteins in the plasmid-containing cells of E. coli, P. putida and P. fluorescens and not in the plasmid-free cells. These may be involved in the efflux of rifampicin.

Bacterial Outer Membrane Proteins↗
PubMed1998

Maintenance of a Pseudomonas fluorescens plasmid in heterologous hosts: metabolic burden as a more reliable variable to predict plasmid instability.

The stability of a large, multiresistance plasmid, pSCL of P. fluorescens CAS102 was studied in Pseudomonas putida and E. coli under various non-stress conditions. Both the strains lost the plasmid within 25 days when repeatedly subcultured in LB broth without any antibiotic. The transformants survived in sterile soil and water without any marked reduction in the viability. In sterile soil, P. putida lost 93% and E. coli, 98% of their plasmid containing population in 30 days, while in sterile water the plasmid loss was 92.5% and 97% respectively. The two variables, viz. the efficiency of plasmid-partitioning during cell division and measurement of relative specific growth rates of plasmid-plus and plasmid-minus cells which are used to predict plasmid instability cannot be used to predict plasmid loss during starvation. The utility of a third variable, viz. the metabolic burden due to plasmid maintenance in predicting plasmid instability in different hosts is discussed. The rate of plasmid loss was found to be comparatively faster in E. coli than in P. putida. The biosynthetic burden due to plasmid maintenance was also more in E. coli than in P. putida when compared to the plasmid-plus and plasmid-minus cells of the two strains which was evident from the increased nutrient uptake rates (glucose, O2, and amino acid) and increased protein content of the plasmid-plus cells of E. coli. From the results, a correlation could be found between the degree of metabolic burden and the rate of plasmid loss. The reliability of metabolic burden, to predict plasmid instability versus the relative specific growth rates is discussed.

Drug Resistance, Multiple↗