Post-translational control of cardiac hemodynamics through myosin binding protein C

Cardiac myosin binding protein C (cMyBP-C) is an integral sarcomeric protein that associates with the thick, thin, and titin filament systems in the contractile apparatus. Three different isoforms of MyBP-C exist in mammalian muscle: slow skeletal (MyBPC1), fast skeletal (MyBP-C2, with several variants), and cardiac (cMyBP-C). Genetic screening studies show that mutations in MYBPC3 occur frequently and are responsible for as many as 30–35 % of identified cases of familial hypertrophic cardiomyopathy. The function of cMyBP-C is stringently regulated by its post-translational modification. In particular, the addition of phosphate groups occurs with high frequency on certain serine residues that are located in the cardiac-specific regulatory M domain. Phosphorylation of this domain has been extensively studied in vitro and in vivo. Phosphorylation of the M domain can regulate the manner in which actin and myosin interact, affecting the cross bridge cycle and ultimately, cardiac hemodynamics.     

Effect of volume of porogens on the porosity of PLGA scaffolds in pH-controlled environment

Poly(lactic-co-glycolic acid) (PLGA) is a well-studied biodegradable polymer used in drug delivery and other medical applications such as in tissue regeneration. It is often necessary to impart porosity within the scaffold (microparticles) in order to promote the growth of tissue during the regeneration process. Sodium chloride and ammonium bicarbonate have been extensively used as porogens in the generation of porous microstructure. In this study, we compared the effect of volumes (250?μl, 500?μl and 750?μl) of two porogens, sodium chloride (1.71 M) and ammonium bicarbonate (1.71 M), on the porosity of PLGA microparticles.     

Granulomatous and lymphocytic hypophysitis – are they immunologically distinct?

Hypophysitis includes three histopathologically distinct entities – granulomatous, lymphocytic and xanthomatous forms. Etiopathogenesis and the immunological differences among these is not well characterized. This study aims to explore the immunopathogenesis of granulomatous and lymphocytic forms of hypophysitis. Demographic, clinical, endocrine function and radiological features of 33 histologically confirmed cases of hypophysitis were reviewed. Immunophenotyping of inflammatory component was performed in 13/33 cases. Visual disturbances (46%), headache (36%), polyuria/polydipsia (6%), menstrual disturbance (6%) and galactorrhoea (6%) were the frequent presenting symptoms. Endocrine abnormalities were noted in 11/18 cases evaluated (61%). Hypothyroidism was the most common endocrine abnormality (33.33%) followed by hyperprolactinaemia (22%) and hypocortisolism (16.66%). On neuroimaging, sellar mass with variable contrast enhancement was observed. On histology, granulomatous hypophysitis (GH) was more common (84.84%) than lymphocytic hypophysitis (LH) (15.15%). In GH, the infiltrate had almost equal proportions of CD3+ T cells and CD68+ histiocytes. Cytotoxic T cells (CD8+) predominated [CD4:CD8 < 1]. CD20+ B cell component ranged from <5% to 50%. Fibrosis, necrosis and giant cells accompanied GH. LH in contrast, had CD4+ T‐helper cell predominance [CD4: CD8 > 1]. CD68+ histiocytes constituted <20% and CD20+ B cells, 5–40% of the infiltrates. In conclusion, GH revealed cytotoxic T cell and histiocyte rich infiltrate in contrast to CD4+ T‐cell predominance in LH suggesting that the two forms have distinct immunological mechanisms in evolution, an autoimmune process in LH and type IV hypersensitivity response in GH.