Biaxial incremental homeostatic elastic moduli of coronary artery: two-layer model

The detailed mechanical properties of various layers of the coronary artery are important for understanding the function of the vessel. The present article is focused on the determination of the incremental modulus in different layers and directions in the neighborhood of the in vivo state. The incremental modulus can be defined for any material subjected to a large deformation if small perturbations in strain lead to small perturbations of stresses in a linear fashion. This analysis was applied to the porcine coronary artery, which was treated as a two-layered structure consisting of an inner intima-media layer and an outer adventitia layer. We adopted a theory based on small-perturbation experiments at homeostatic conditions for determination of incremental moduli in circumferential, axial, and cross directions in the two layers. The experiments were based on inflation and axial stretch. We demonstrate that under homeostatic conditions the incremental moduli are layer- and direction dependent. The incremental modulus is highest in the circumferential direction. Furthermore, in the circumferential direction, the media is stiffer than the whole wall, which is stiffer than the adventitia. In the axial direction, the adventitia is stiffer than the intact wall, which is stiffer than the media. Hence, the coronary artery must be treated as a composite, nonisotropic body. The data acquire physiological relevance in relation to coronary artery health and disease.     

Cytology of nipple discharge in florid gynecomastia

OBJECTIVE: To determine the cytomorphologic spectrum of nipple discharge in florid gynecomastia. STUDY DESIGN: During a 22-year period (July 1979-June 2001), nipple discharge from nine males with breast lesions were examined. Smears from four of these cases with histologically documented gynecomastia were reviewed along with the tissue sections. RESULTS: In the three patients with florid gynecomastia the smears were cellular, with numerous benign ductal cells and papillary fragments along with foam cells and inflammatory cells. Epithelial atypia was mild in two cases and moderate in one. One of the three cases had an associated breast lump that showed features of florid gynecomastia on fine needle aspiration cytology. The biopsy from this case showed cystic hyperplasia of the breast similar to that in women with an intraductal papilloma. One case of simple gynecomastia on histology showed two fragments of benign ductal cells with occasional apocrine and foam cells. CONCLUSION: Nipple discharge in florid gynecomastia may pose problems in identification as the cellularity and atypia may lead to a misdiagnosis of carcinoma.     

Enhanced protection by melatonin and meloxicam combination in a middle cerebral artery occlusion model of acute ischemic stroke in rat

Mixed efficacy of neuroprotective drugs in clinical trials has led to the emergence of the approach of combination therapy in stroke. The present study was carried out to investigate the effect of the combination of melatonin (potent antioxidant) and meloxicam (preferential inhibitor of cyclooxygenase-2 enzyme) against a middle cerebral artery occlusion model of stroke in rats. Male Wistar rats in the weight range of 250-300 g were used. Rats were anesthetized using chloral hydrate (400 mg/kg i.p) and subjected to 2 h of transient middle cerebral artery occlusion. Melatonin was administered at a dose of 20 mg/kg i.p. four times: at the time of middle cerebral artery occlusion, 1.5 h after middle cerebral artery occlusion, at the time of reperfusion, and 1 h after reperfusion. Meloxicam (2.5 mg/kg) was administered 4 h after middle cerebral artery occlusion. Motor performance tests (grip test, foot fault test, rotarod performance test, spontaneous locomotor activity), markers of oxidative stress, and triphenyltetrazolium chloride staining were carried out 24 h after middle cerebral artery occlusion. A vehicle-treated group was run in parallel. It was observed that melatonin treatment improved the motor performance and significantly attenuated the levels of malondialdehyde (MDA) as compared with the middle cerebral artery occluded group. Meloxicam treatment at the dose used neither showed significant improvement on the motor performance nor decreased the levels of MDA significantly as compared with the middle cerebral artery occluded group. However, when the combination of the two drugs was used, better protection was observed as was evident by the significant decrease in the percent foot fault errors, the increase in the time spent on the rotarod, and the increase in the six-point neurological score and grip test score. There was also a significant decrease in the levels of MDA in the combination group. The results of the present study demonstrate that enhanced protection is observed with the use of a combination of melatonin plus meloxicam in the middle cerebral artery occlusion model of acute ischemic stroke in rats.     

Synthesis and biological activity of selective pipecolic acid-based TNF-alpha converting enzyme (TACE) inhibitors

A series of novel, selective TNF-alpha converting enzyme inhibitors based on 4-hydroxy and 5-hydroxy pipecolate hydroxamic acid scaffolds is described. The potency and selectivity of TACE inhibition is dramatically influenced by the nature of the sulfonamide group which interacts with the S1' site of the enzyme. Substituted 4-benzyloxybenzenesulfonamides exhibit excellent TACE potency with >100x selectivity over inhibition of matrix metalloprotease-1 (MMP-1). Alkyl substituents on the ortho position of the benzyl ether moiety give the most potent inhibition of TNF-alpha release in LPS-treated human whole blood.     

MRD: a microsatellite repeats database for prokaryotic and eukaryotic genomes

MRD is a database system to access the microsatellite repeats information of genomes such as archea, eubacteria, and other eukaryotic genomes whose sequence information is available in public domains. MRD stores information about simple tandemly repeated k-mer sequences where k= 1 to 6, i.e. monomer to hexamer. The web interface allows the users to search for the repeat of their interest and to know about the association of the repeat with genes and genomic regions in the specific organism. The data contains the abundance and distribution of microsatellites in the coding and non-coding regions of the genome. The exact location of repeats with respect to genomic regions of interest (such as UTR, exon, intron or intergenic regions) whichever is applicable to organism is highlighted. MRD is available on the World Wide Web at and/or . The database is designed as an open-ended system to accommodate the microsatellite repeats information of other genomes whose complete sequences will be available in future through public domain.     

Molecular dynamics simulation of dipalmitoylphosphatidylserine bilayer with Na+ counterions

We performed a molecular dynamics simulation of dipalmitoylphosphatidylserine (DPPS) bilayer with Na+ counterions. We found that hydrogen bonding between the NH group and the phosphate group leads to a reduction in the area per headgroup when compared to the area in dipalmitoylphosphatidylcholine bilayer. The Na+ ions bind to the oxygen in the carboxyl group of serine, thus giving rise to a dipolar bilayer similar to dipalmitoylphosphatidylethanolamine bilayer. The results of the simulation show that counterions play a crucial role in determining the structural and electrostatic properties of DPPS bilayer.     

In vitro and in vivo inhibition of telomerase activity from Chinese hamster V79 cells

While studying the inhibition of telomerase activity in Chinese hamster V79 cells using polymerase chain reaction (PCR) based telomeric repeat amplification protocol (TRAP) assay, we had earlier observed that 7-deaza deoxy guanosine triphosphate (7-deaza dGTP) and oligonucleotide (TTAGGG)4 inhibited telomerase activity in vitro. In the present study, we report inhibition of telomerase activity by modified base 7-deaza deoxy adenosine triphosphate (7-deaza dATP) and phosphorothioate TTAGGG (PS-TTAGGG). Both the compounds inhibited telomerase activity in a concentration dependent manner; 8.5 microM of 7-deaza dATP and 0.1 microM of PS-TTAGGG being the concentration for 50% of the maximum inhibition. This observation supports our earlier hypothesis that incorporation of a modified nucleotide into telomere possibly interferes with the recognition of the telomerase and TTAGGG interferes with the RNA component of telomerase. We have further shown that treatment of cells with nicotinamide (NA) and benzamide (BA), well known inhibitors of poly (ADP-ribose) polymerase, reduced telomerase activity. We speculate that modification of the telomeric binding proteins or other components by poly (ADP-ribosyl)ation may be involved in such inhibition.     

Multiple-impeller systems with a special emphasis on bioreactors: a critical review

The multiple-impeller agitated systems are compared with single-impeller agitated systems with a special focus on its applications for bioreactors. Correlations reported in the literature for gas phase hold-up, mass transfer coefficient and power consumption under gassed and ungassed conditions are compared and recommendations have been made regarding their suitability for design and scale-up of bioreactors. The multiple-impeller systems are found to be superior as compared to single-impeller systems in all the above mentioned aspects, except liquid mixing. For all kinds of reactors where the sole purpose is mass transfer, multiple-impeller systems are advantageous and there would be large savings on an industrial scale, especially for the bioreactors where the reaction periods are long and the power consumption cost could be a significant component to the overall production costs.     

Ribonuclease from cobra snake venom: purification by affinity chromatography and further characterization

A ribonuclease from cobra snake venom was isolated and purified to homogeneity using antibody-affinity chromatography, increasing the yield fourfold. The purified enzyme showed cytidylic acid specificity, as reported earlier. Further, the effects of temperature, pH, metal ions, inhibitors, and urea on the enzyme activity were studied. Snake venom RNase exhibited salt-dependent reversible association-dissociation behaviour. Immunological studies indicate that this enzyme shares one of the antigenic sites of RNase A. The partial N-terminal sequence of the enzyme showed considerable homology with phospholipases from snake venom; however, the enzyme itself did not show any phospholipase activity.