Involvement of mast cells in monocrotaline-induced pulmonary hypertension in rats

Background: Mast cells (MCs) are implicated in inflammation and tissue remodeling. Accumulation of lung MCs is described in pulmonary hypertension (PH); however, whether MC degranulation and c-kit, a tyrosine kinase receptor critically involved in MC biology, contribute to the pathogenesis and progression of PH has not been fully explored.Methods: Pulmonary MCs of idiopathic pulmonary arterial hypertension (IPAH) patients and monocrotaline-injected rats (MCT-rats) were examined by histochemistry and morphometry. Effects of the specific c-kit inhibitor PLX and MC stabilizer cromolyn sodium salt (CSS) were investigated in MCT-rats both by the preventive and therapeutic approaches. Hemodynamic and right ventricular hypertrophy measurements, pulmonary vascular morphometry and analysis of pulmonary MC localization/counts/activation were performed in animal model studies.Results: There was a prevalence of pulmonary MCs in IPAH patients and MCT-rats as compared to the donors and healthy rats, respectively. Notably, the perivascular MCs were increased and a majority of them were degranulated in lungs of IPAH patients and MCT-rats (p < 0.05 versus donor and control, respectively). In MCT-rats, the pharmacological inhibitions of MC degranulation and c-kit with CSS and PLX, respectively by a preventive approach (treatment from day 1 to 21 of MCT-injection) significantly attenuated right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH). Moreover, vascular remodeling, as evident from the significantly decreased muscularization and medial wall thickness of distal pulmonary vessels, was improved. However, treatments with CSS and PLX by a therapeutic approach (from day 21 to 35 of MCT-injection) neither improved hemodynamics and RVH nor vascular remodeling.Conclusions: The accumulation and activation of perivascular MCs in the lungs are the histopathological features present in clinical (IPAH patients) and experimental (MCT-rats) PH. Moreover, the accumulation and activation of MCs in the lungs contribute to the development of PH in MCT-rats. Our findings reveal an important pathophysiological insight into the role of MCs in the pathogenesis of PH in MCT- rats

Pharmacological targeting of the KIT growth factor receptor: a therapeutic consideration for mast cell disorders

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72410/1/bjp.2008.204.pd

Water soluble binder for fabrication of Li4Ti5O12 electrodes

Less expensive and greener aqueous electrode preparation processes are essential for the market penetration of lithium ion batteries to mid-scale applications. So far only carboxyl methyl cellulose (CMC) binder has been adopted for industrial use to fabricate carbon electrodes without harmful organic solvents but this process is prone to bacterial growth. In this study a new binder candidate, Acryl S020, is introduced for an aqueous preparation process that has been used for preparing Li4Ti5O12 electrodes for lithium ion batteries. It is shown that with our water based process electrodes with capacities comparable to those electrodes fabricated with the conventional organic solvent based process with the PVDF binder are obtained. Moreover, our lithium titanate electrodes with the Acryl S020 binder show high capacity retention and they can be operated at sub-zero temperatures. Electrodes were also fabricated with pilot-scale gravure printing and slot-die coating methods and they showed stable cycles lives of 500 cycles.Peer reviewe