The physiological response of fishes to a deficiency of cyanocobalamin and folic acid

Environmental adaptive response of fishes to the nutritional deficiencies of two important vitamins of the B-group viz . cyanocobalamin and folacin has been investigated using growth, haematology and haemopoiesis as physiological indices. Extended studies lasting 105 days revealed a consistent decrease in growth or even loss of weight when cyanocobalamin and folacin were absent from the diet. The combined deficiency of these two vitamins had an additive rather than synergistic effect on growth. The feed conversion values of all the deficient groups were significantly low as compared to the control. Haematologically the occurrence of anaemia and leucocytosis were recorded in all the deficient groups, the former mainly of megaloblastic type. Differential WBC counts revealed that leucocytosis was mainly due to an increase in thrombocyte population and cosinophils. On the other hand, there was an relative decrease of other nongranulocytes and granulocytes. Erythro-poietic investigations revealed a decreased proliferation rate of the reticuloendothelial cells and an increased number of young and mature reticulocytes and immature erythrocytes into the peripheral blood.     

An experimental model of ameboma in guinea pig.

Among the wide variety of clinicopathological manifestations of intestinal amebiasis, amebomas occur rarely and their pathogenesis is not well understood. When cholesterol-fed, 2- to 4-week-old guinea pigs were infected intracecally with a virulent, monoaxenic strain of Entamoeba histolytica, gross and histologically characteristic amebomas developed in 85% of the animals by the 3rd day, in 94% by the 9th day, and in 96% by the 12th day postinfection, by which time most of them had died. Amebomas were confirmed by histopathology. Thus, a model of consistent production of amebomas was documented.     

Evidence for the involvement of multiple pathways in the biodegradation of 1- and 2-methylnaphthalene by Pseudomonas putida CSV86

Pseudomonas putida CSV86, a soil bacterium, grows on 1- and 2-methylnaphthalene as the sole source of carbon and energy. In order to deduce the pathways for the biodegradation of 1- and 2-methylnaphthalene, metabolites were isolated from the spent medium and purified by thin layer chromatography. Emphasis has been placed on the structural characterisation of isolated intermediates by GC-MS, demonstration of enzyme activities in the cell free extracts and measurement of oxygen uptake by whole cells in the presence of various probable metabolic intermediates. The data obtained from such a study suggest the possibility of occurrence of multiple pathways in the degradation of 1- and 2-methylnaphthalene. We propose that, in one of the pathways, the aromatic ring adjacent to the one bearing the methyl moiety is oxidized leading to the formation of methylsalicylates and methylcatechols. In another pathway the methyl side chain is hydroxylated to-CH₂OH which is further converted to-CHO and-COOH resulting in the formation of naphthoic acid as the end product. In addition to this, 2-hydroxymethylnaphthalene formed by the hydroxylation of the methyl group of 2-methylnaphthalene undergoes aromatic ring hydroxylation. The resultant dihydrodiol is further oxidised by a series of enzyme catalysed reactions to form 4-hydroxymethyl catechol as the end product of the pathway.     

Discovery of thiazolyl-phthalazinone acetamides as potent glucose uptake activators via high-throughput screening

With the aim to discover orally active small molecules that stimulate glucose uptake, high throughput screening of a library of 5000 drug-like compounds was conducted in differentiated skeletal muscle cells in presence of insulin. N-Substituted phthalazinone acetamide was identified as a potential glucose uptake modulator. Several novel derivatives were synthesized to establish structure activity relationships. Identified lead thiazolyl-phthalazinone acetamide (7114863) increased glucose uptake (EC₅₀ of 0.07 ± 0.02 μM) in differentiated skeletal muscle cells in presence of insulin. Furthermore, 7114863 was superior to rosiglitazone under similar experimental conditions without inducing PPAR-γ agonist activity thus making it a very interesting scaffold.