Showing papers by "Sujeet Kumar published in 2013"

Cardiomyocyte culture - an update on the in vitro cardiovascular model and future challenges.

Abstract: The success of any work with isolated cardiomyocytes depends on the reproducibility of cell isolation, because the cells do not divide. To date, there is no suitable in vitro model to study human adult cardiac cell biology. Although embryonic stem cells and induced pluripotent stem cells are able to differentiate into cardiomyocytes in vitro, the efficiency of this process is low. Isolation and expansion of human cardiomyocyte progenitor cells from cardiac surgical waste or, alternatively, from fetal heart tissue is another option. However, to overcome various issues related to human tissue usage, especially ethical concerns, researchers use large- and small-animal models to study cardiac pathophysiology. A simple model to study the changes at the cellular level is cultures of cardiomyocytes. Although primary murine cardiomyocyte cultures have their own advantages and drawbacks, alternative strategies have been developed in the last two decades to minimise animal usage and interspecies differences. This review discusses the use of freshly isolated murine cardiomyocytes and cardiomyocyte alternatives for use in cardiac disease models and other related studies.

Synthesis and biological evaluation of 2-(5-substituted-1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)-N-substituted-hydrazinecarbothioamides

Abstract: Various 5-substituted-2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)hydrazinecarbothioamide (4a, b) and 5-substituted-2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)-N-(phenyl-4-substituted)hydrazinecarbothioamide (5a–h) derivatives were synthesized. The compounds were screened for cytotoxicity against human HeLa and CEM T-lymphocytes as well as murine L1210 cells. The compounds were also screened for β-lactamase inhibitory activity, antiviral, antibacterial, and antifungal activity against various strains of microorganisms. Several of these compounds were endowed with low micromolar 50 %-cytostatic concentration (IC50) values, and some were virtually equally potent as melphalan. The most potent inhibitors against the murine leukemia cells (L1210) were also the most inhibitory against human T-lymphocyte (CEM) tumor cells. Derivative 2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)-N-(4-methoxyphenyl)hydrazinecarbothioamide 5c emerged as the most potent cytostatic compound among the tested compounds. Derivatives 4b, 5a, 5b, and 5d showed antiviral activity against HEL cell cultures (IC50 11–20 μM). Moderate antimicrobial activity was observed for all derivatives. The encouraging cytostatic and antiviral activity data provide an adequate rationale for further modification of these molecular scaffolds. Derivative 5c (1.9–4.4 μM) emerged as the most potent cytostatic compound among the tested compounds. Derivatives 4b, 5a, 5b, and 5d showed antiviral activity against HEL cell cultures (IC50 11–20 μM).

Role of Calpains in Calmodulin Regulated Systems

Abstract: Dysregulation of proteolytic enzymes may disrupt normal biological processes in myocardium can lead to various cardiac conditions. Substantial evidence supports the involvement of matrix metalloproteinase, cystine and serine protease families in this process. Calpain is an intracellular Ca2+-activated protease. Deregulation of calpain caused by a disruption of calcium homeostasis during cardiac pathologies such as atrial fibrillation, heart failure, hypertrophy, or ischemia reperfusion, and thus the myocardial damage. Calpain-calcineurin signalling is pivotal in cardiac conditions especially ischemia, since the signalling produces a cascading effect on the outcome of ischemia. The cleavage of phosphodiesterase1 by calpain is crucial for the regulation of cyclic nucleotides especially cAMP and cGMP. Turnover of cAMP and cGMP in cardiac tissue determines how the cells respond and survive to ischemic insult. Among the known calpain inhibitors, the most specific and potent inhibitor is calpastatin, which belongs to the calpain family. Further research on calpain structures will help in determining the conditions required for activation and the ability of calpain specifically proteolyse even untagged substrates. Though many interesting reviews have covered on the entire calpain system, the current manuscript focuses on the research carried out on calpains in relation to cardiac system by describing their interaction with 2 important cardiac specific proteins—calcineurin and phosphodiesterase 1.