Single-dose pharmacokinetics and cardiovascular effects of oral pimobendan in healthy cats

Abstract not availableM. Yata, A.J. McLachlan, D.J.R. Foster, A.S. Hanzlicek, N.J. Beijerin

Pharmacokinetics and cardiovascular effects following a single oral administration of a nonaqueous pimobendan solution in healthy dogs

Pimobendan is an inodilator used in the treatment of canine congestive heart failure (CHF). The aim of this study was to investigate the pharmacokinetics and cardiovascular effects of a nonaqueous oral solution of pimobendan using a single-dose, operator-blinded, parallel-dose study design. Eight healthy dogs were divided into two treatment groups consisting of water (negative control) and pimobendan solution. Plasma samples and noninvasive measures of cardiovascular function were obtained over a 24-h period following dosing. Pimobendan and its active metabolite were quantified using an ultra-high-performance liquid chromatography-mass spectrometer (UHPLC-MS) assay. The oral pimobendan solution was rapidly absorbed [time taken to reach maximum concentration (Tmax ) 1.1 h] and readily converted to the active metabolite (metabolite Tmax 1.3 h). The elimination half-life was short for both pimobendan and its active metabolite (0.9 and 1.6 h, respectively). Maximal cardiovascular effects occurred at 2-4 h after a single oral dose, with measurable effects occurring primarily in echocardiographic indices of systolic function. Significant effects persisted for <8 h. The pimobendan nonaqueous oral solution was well tolerated by study dogs.M. Yata, A. J. Mclachlan, D. J. R. Foster, S. W. Page and N. J. Beijerin

Ecophysiology and application of acidophilic sulfur-reducing microorganisms

Sulfur-reducing prokaryotes play an important role in the sulfur biogeochemical cycle, especially in deep-sea vents, hot springs and other extreme environments. The reduction of elemental sulfur is not very favorable thermodynamically, but still provides enough energy for growth of microorganisms. Currently known sulfur reducers are spread over about 69 genera within 9 phyla in the Bacteria domain and 37 genera within 2 phyla in the Archaea domain. Elemental sulfur reduction can occur with polysulfide as an intermediate or via direct cell attachment to the solid substrate. At least four different enzymes are involved in those pathways, and these enzymes are also detected in several microorganisms that are potential sulfur reducers, but not reported as such in literature so far. The ecological distribution of sulfur respiration seems to be more widespread at high temperatures with neutral pH. However, some sulfur reducers can grow at pH as low as 1. The sulfide produced from sulfur reduction can selectively precipitate metals by varying the pH values from 2 to 7, depending on the target metal. Therefore, acidophilic sulfur reducers are of particular interest for application in selective precipitation and recovery of heavy metals from metalliferous waste streams. This chapter explores the ecology and physiology of elemental sulfur reducers, and discusses technologies that can be set up to exploit acidophilic sulfur reducers.The doctoral study program of A.P. Florentino is supported by the organization of the Brazilian Government for the development of Science and Technology CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico). Research of I. Sánchez-Andrea and A.J.M. Stams is financed by ERC grant project 323009 and by Gravitation grant project 024.002.002 from the Netherlands Ministry of Education, Culture and Science