Effects of detergents on Ca2+-activated neural proteinase activity (calpain) in neural and non-neural tissue: A comparative study

Calcium activated neutral proteinase (mcalpain) activity was determined in brain and other tissue of rat. More than 60% of the brain mcalpain activity was present in the particulate fraction while only 30% was in cytosol. In contrast, particulate fractions of liver, kidney, muscle, and heart contained about 8–12% of tissue mcalpain activity while 88% was present in cytosol. Removal of the endogenous inhibitor calpastatin increased the tissue mcalpain activity severalfold. Triton X-100 and deoxycholate (DOC) stimulated the neural calpain activity by ten-fold while activity in non-neural tissue was unaffected. Incubation with other detergents, e.g. Triton N-57 and thioglucopyranoside, stimulated brain calpain activity five-fold while Brij-35 did not have any effect. Sodiumdodecylsulphate (SDS), on the other hand, inhibited the enzyme activity. Brain contained the lowest calpain activity compared to non-neural tissue. The calpain activity in muscle, kidney and heart was three-fold greater than liver. Immunoblot identification of the enzyme revealed that calpain was predominantly in the particulate fraction and less in cytosol of brain while it was present mainly in cytosol and less in the pellet fractions of non-neural tissue.     

Synthesis of anticancer beta-lactams: mechanism of action

Synthesis of the trans 1-N-chrysenyl and 1-N-phenanthrenyl 3-acetoxy-4-phenyl-2-azetidinones has been achieved. Microwave-assisted reaction has proved useful in the synthesis of these compounds. Cell growth inhibition study has indicated selective anticancer activity against two leukemia and colon carcinoma cell lines. A mechanistic correlation of their anticancer activity has been described. Striking G2 blockade that is clearly distinct in cell cycle analysis and demonstrated only in sensitive cell lines has been observed. They do not induce apoptosis in sensitive or resistant lines. They also do not inhibit topoisomerases. Ames test has shown they are nonmutagenic.     

Acute Multiple Sclerosis Characterized by Extensive Mononuclear Phagocyte Infiltration

In this study, we examine the clinical, neuroradiological, and immunohistochemical findings of a 51 year old white female who died 27 months after onset of acute multiple sclerosis despite treatment with interferon-, azathioprine, corticosteroids, and cyclophosphamide. Immunohistochemical studies revealed extensive gliosis and mononuclear phagocyte infiltration with corresponding upregulation of proinflammatory cytokines (eg. IFN-, TNF-). The significance of immunohistochemical findings with respect to clinical presentation is discussed.     

Polycyclic aromatic compounds as anticancer agents: synthesis and biological evaluation of dibenzofluorene derivatives

Highly regioselective electrophilic substitution of dibenzofluorene was achieved and the nitro derivative was transformed to a variety of new anticancer agents.     

Polycyclic aromatic compounds as anticancer agents: structure-activity relationships of chrysene and pyrene derivatives

A large number of diamides and diamines were synthesized using 6-amino chrysene and 1-amino pyrene as starting materials. A structure activity study with cis-platinum as internal control against animal and human tumor lines was carried out in vitro. This study indicated that the in vitro cytotoxicity toward these lines depends on the functionality present in the molecules. The diamino compounds were found to be more potent than the diamides, and these were equally active irrespective of the end heterocyclic group, whereas the activity of the diamides was strongly dependent on the terminal unit. In general, the diamides containing chrysene as the chromophore were more active than those with a pyrene ring. The size of the end heterocyclic ring, along with the nature of the spacer connecting the polycyclic ring to the heterocyclic ring, seemed to affect the biological activity in certain cell lines. Hemolysis experiments on a lead compound established that it had activities similar to those described for membrane-stabilizing agents. This agent also demonstrated the capacity to produce differentiation in leukemia cell lines.