In Vitro Effects of Pirfenidone on Cardiac Fibroblasts: Proliferation, Myofibroblast Differentiation, Migration and Cytokine Secretion

Cardiac fibroblasts (CFs) are the primary cell type responsible for cardiac fibrosis during pathological myocardial remodeling. Several studies have illustrated that pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) attenuates cardiac fibrosis in different animal models. However, the effects of pirfenidone on cardiac fibroblast behavior have not been examined. In this study, we investigated whether pirfenidone directly modulates cardiac fibroblast behavior that is important in myocardial remodeling such as proliferation, myofibroblast differentiation, migration and cytokine secretion. Fibroblasts were isolated from neonatal rat hearts and bioassays were performed to determine the effects of pirfenidone on fibroblast function. We demonstrated that treatment of CFs with pirfenidone resulted in decreased proliferation, and attenuated fibroblast α-smooth muscle actin expression and collagen contractility. Boyden chamber assay illustrated that pirfenidone inhibited fibroblast migration ability, probably by decreasing the ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1. Furthermore, pirfenidone attenuated the synthesis and secretion of transforming growth factor-β1 but elevated that of interleukin-10. These direct and pleiotropic effects of pirfenidone on cardiac fibroblasts point to its potential use in the treatment of adverse myocardial remodeling

EFFECT OF PLANT GROWTH REGULATORS ON MICROPROPAGATION OF ENDEMIC IRIS STEONPHYLLA HAUSSKN & SIEHE EX BAKER SUBSP. ALLISONII B. MATHEW IN TURKEY

Most geophytes are widely used for pharmaceutical and perfume industry as well as ornamental flowers. Most of them are collected from natural habitats. However, Iris stenophylla Hausskn & Siehe Ex Baker subsp. allisonii B. Mathew is a critically endangered geophyte. Therefore in vitro micropropagation is an important alternative method for the protection and production of this species. We have cultured bulb scale, leaf, skap and immature embryo explants of Iris stenophylla on Murashige-Skoog (MS) media supplementted with various concentrations of plant growth regulators. Immature embryos produced a higher number of bulblets than others. The most bulblets were produced from immature embryos on MS medium supplemented with 1 mg/l BA and 0.25 mg/l NAA. Effective surface sterilization of explants to a level suitable for micropropagation is animportant stage to overcome infection. We report a series of experiments with Iris stenophylla bulbs that involved various concentrations of sodium hypochlorite and HgCl2 treatments of whole bulbs. The best results were obtained from 80% commercial bleach for 20 min. Acknowledgement: This study was supported by the Scientific and Technical Research Council (Project no: TOVAG-105 0 246) of Turke

Using supervised machine learning for large-scale classification in management research: The case for identifying artificial intelligence patents

10.1002/smj.3441STRATEGIC MANAGEMENT JOURNAL442491-51

Haemodynamic and clinical effects of ularitide in decompensated heart failure

Aims: Ularitide is a synthetic form of urodilatin, a natriuretic peptide produced in the kidney with vasodilating, natriuretic, and diuretic effects, that offers promise for the management of decompensated heart failure (DHF). We assessed the efficacy and safety of ularitide in treating patients with DHF. Methods and results: In this Phase II randomized, double-blind, placebo-controlled trial, 221 DHF patients received either placebo (n=53) or ularitide at 7.5 ng/kg/min (n=60), 15 ng/kg/min (n=53), or 30 ng/kg/min (n=55) as a 24-h continuous infusion. At 6 h, ularitide demonstrated a significant decrease in pulmonary capillary wedge pressure (P=0.052, P=0.000004, P=0.000002, respectively) and improved dyspnoea score in the 7.5, 15, and 30 ng/kg/min ularitide group (P=0.0026, P=0.0026, P=0.0013, respectively). Ularitide reduced systemic vascular resistance and increased cardiac index for the 15 and 30 ng/kg/min groups (P=0.017, P=0.00002, respectively). Systolic blood pressure (BP) decreased dose dependency. Heart rate and serum creatinine were unchanged through day 3. Most frequently reported drug-related adverse events through day 3 in all ularitide groups were dose-dependent BP decrease and hypotension. Conclusion: Ularitide lowered cardiac filling pressures and improved dyspnoea without apparent early deleterious effects on renal function in DHF patients. These results suggest that ularitide may play a role in the management of DHF. © The European Society of Cardiology 2006. All rights reserved