Heparanase-induced shedding of syndecan-1/CD138 in myeloma and endothelial cells activates VEGFR2 and an invasive phenotype: prevention by novel synstatins.

Multiple myeloma arises when malignant plasma cells invade and form multiple tumors in the bone marrow. High levels of heparanase (HPSE) correlate with poor prognosis in myeloma patients. A likely target of the enzyme is the heparan sulfate (HS) proteoglycan syndecan-1 (Sdc1, CD138), which is highly expressed on myeloma cells and contributes to poor prognosis in this disease. We find that HPSE promotes an invasive phenotype mediated by the very late antigen-4 (VLA-4, or α4ß1 integrin) in myeloma cells plated on either fibronectin (FN) or vascular endothelial cell adhesion molecule-1 (VCAM-1), ligands that are prevalent in the bone marrow. The phenotype depends on vascular endothelial cell growth factor receptor-2 (VEGFR2), which is aberrantly expressed in myeloma, and is characterized by a highly protrusive lamellipodium and cell invasion. HPSE-mediated trimming of the HS on Sdc1 and subsequent matrix metalloproteinase-9-mediated shedding of the syndecan exposes a juxtamembrane site in Sdc1 that binds VEGFR2 and VLA-4, thereby coupling VEGFR2 to the integrin. Shed Sdc1 can be mimicked by recombinant Sdc1 ectodomain or by a peptide based on its binding motif, which causes VLA-4 to re-orient from the lagging edge (uropod) to the leading edge of migrating cells, couple with and activate VEGFR2. Peptides (called 'synstatins') containing only the VLA-4 or VEGFR2 binding sites competitively inhibit invasion, as they block coupling of the receptors. This mechanism is also utilized by vascular endothelial cells, in which it is also activated by HPSE, during endothelial cell tube formation. Collectively, our findings reveal for the first time the mechanism through which HPSE modulates Sdc1 function to promote both tumor cell invasion and angiogenesis, thereby driving multiple myeloma progression. The inhibitory synstatins, or inhibitors of HPSE enzyme activity, are likely to show promise as therapeutics against myeloma extravasation and spread.

Managing ascites in patients with chronic liver disease.

This article discusses the pathophysiology of ascites, a complication associated with chronic liver disease. The diagnosis and grading of ascites and assessment of patients with the condition are explored. In addition, the nursing and medical management of ascites is discussed, and recommendations for interdisciplinary working and education are suggested. Nursing knowledge of this complication is essential to ensure that patients with ascites are cared for effectively and that their comfort is maximised.

Physico-chemical and microbial characteristics of the coral reef environment of the Gulf of Mannar marine biosphere reserve, India.

Investigation on physico-chemical parameters and bacteial characteristics of the coral reef environs of the Gulf of Mannar biosphere reserve was studied. The study found the influence of different physico-chemical parameters on one another and also on the distribution of the total heterotrophic bacteria (THB) in the coral reef areas. Nutrients exhibited considerable seasonal and spatial variations with influence on the bacterial population. Coral reef areas recorded higher bacterial population density both in water (3.5 to 18 x 10(5) CFU ml(-1)) and sediment (1 to 14 x 10(7) CFU g(-1)) samples than the non coral reef areas (3.4 to 10.5 x 10(4) CFU ml(-1) in water and 0.9 to 7 x 10(6) CFU g(-1)). The study also found the dominance of gram negative groups at all the three stations (64.73, 63,5 and 72.59%) with Pseudomonas contributing maximum number of strains in all the samples. In addition Vibrio, Aeromonas, Flavobacterium, Cytophaga, Enterobacter and Alcaligenes were also recorded. The gram positive group was represented by Bacillus, Micrococcus, Arthrobacter and Corynebacterium. The genetic composition of THB isolated from the coral mucus revealed the presence of Vibrio and Micrococcus in all the coral mucus.

Effect of probiotics on bacterial population and health status of shrimp in culture pond ecosystem.

The artificially manufactured probiotics having beneficial bacteria, Bacillus spp. was applied regularly in a modified extensive shrimp (Penaeus monodon) culture pond, located on the bank of Vellar estuary, Parangipettai. The populations of total heterotrophic bacteria (THB), beneficial bacteria (Bacillus spp.) and pathogenic bacteria (vibrios) were monitored in water and sediment of the pond. The results were compared with a control pond, situated in the same location having same water spread area, stocking density, species managed with same technologies and optimum environmental parameters in which no probiotic was applied. The populations of THB and Bacillus spp. in the experimental pond increased and the vibrios decreased after each application of probiotics. But the result of the control pond showed an increasing trend of the populations of THB, Bacillus spp. and vibrios towards days of culture. The control pond had lower levels of THB and Bacillus spp. and higher levels of vibrios than the probiotic applied (experimental) pond. Also the probiotics maintained optimum transparency and low organic load in the experimental pond as compared to control. In general, water and sediment had almost equal number of Bacillus spp. and vibrios, but sediment had higher THB load than water. The applications of probiotics lesser pathogenic vibrios and enhance beneficial bacilli in the culture leading to improved water quality, promoted growth and survival rates and increased the health status of the shrimp without stress and disease outbreaks. Thus the application of probiotics could lead to disease-free and profitable shrimp culture operations which will be helpful for shrimp farmers as most of them are now-a-days severely affected by microbial diseases.

Antibiotic-resistant Vibrio cholerae in Parangipettai coastal environs, south east India.

This study was undertaken to determine the comparative incidence of drug-resistant Vibrio cholerae non-01 in the environmental samples (water, sediment, and plankton) and in the seafood samples (finfish, shellfish, and crustacean) of estuarine, coastal, and mangrove communities. A total of 770 V. cholerae isolates were examined--all of the strains were sensitive to 100% against cephalothin (30 mcg), chloramphenical (30 mcg), and polymyxin-B (300 mcg). However, all of the strains isolated form environmental and seafood samples showed higher resistance (> 25%) to oxytetracycline, streptomycin, sulphadiazine, tetracycline, and to streptomycin, sulphadiazine, and tetracycline, respectively. The percentage of strains resistant to other antimicrobial substances depended on the antibiotic and on the isolation source. Among the isolates tested, a significantly higher number of drug-resistant bacteria was found to occur in water and finfish samples.

Preliminary investigation on antibacterial activity of some marine diatoms.

Seven species of marine diatoms were cultured under defined laboratory conditions. Air dried algal powder was used for extraction with different solvents in sequence. The algal extracts were tested against various bacteria by paper disc method. Nitzschia longissma, Skeletonema costatum and Biddulphia sinensis were effective against the test bacteria. Hemidiscus hardmannianus, Coscinodiscus centralis and Asterionella japonica showed moderate antibacterial activity. Pleurosigma elongatum exhibited no activity. The antibacterial substances were fully extracted by the organic solvents. Only in the active algal species, was activity noted in the aqueous extracts.