Comparative effects of rifabutin and rifampicin on cytochromes P450 and UDP-glucuronosyl-transferases expression in fresh and cryopreserved human hepatocytes.

The aim of this study was to evaluate rifabutin (RBT) and rifampicin (RIF) capabilities in inducing various xenobiotic metabolizing enzymes such as cytochromes P450 (CYPs) and UDP-glucuronosyl-transferases (UGTs) in cultured fresh and cryopreserved human hepatocytes. Enzyme induction was assessed through the use of several diagnostic markers, i.e. testosterone, midazolam (MDZ), diazepam (DZP) and 7-ethoxyresorufin for CYP-dependent enzyme reactions; and AZT for UGT-dependent enzyme reactions. RBT concentrations (0.118, 0.708 microM) were selected according to previously published pharmacokinetic data in patients. The known CYP3A4 inducer in humans, RIF, was used as a positive control. At the concentrations used, no sign of cytotoxicity was evidenced. Both compounds were able to dose-dependently induce the overall metabolism of testosterone (approximately 2-fold for RBT, 4-fold for RIF) and the formation of the 6beta-hydroxylated-derivative (up to approximately 4-fold over control for RBT and approximately 10-fold for RIF), which is CYP3A4 dependent. The other hydroxylated metabolites (16alpha-OH and 2alpha-OH) were also enhanced. The metabolism of MDZ, which is specifically metabolized by CYP3A4 in humans, was also investigated following drug's exposure to hepatocytes. DZP one, which is governed by various CYPs, including CYP3A, was also investigated. RBT was shown to increase the biotransformation of both benzodiazepines (approximately 1.9-fold over control). Moreover, the effects of both drugs on ethoxyresorufin O-deethylase activity (EROD), which is representative of CYPIA1/2 isoforms, were tested. Results showed only a moderate induction of this marker (approximately 2-fold over control) when compared to the high effect observed after hepatocyte exposure to 3-methylcholantene (approximately 14-fold over control). Finally, the action of RBT and RIF on UGTs expression was investigated by using AZT as diagnostic substrate: glucuronides formation was not significantly affected by the two rifamycin derivatives. On the whole, exposure of fresh or cryopreserved human hepatocytes to RBT dose-dependently affected the levels of drug metabolizing enzymes in a dose-dependent manner. However, as already demonstrated by in vivo pharmacokinetic studies, its inducing properties towards CYPs, CYP3A in particular, are less pronounced than RIF.     

Exercise training in heart failure

Chronic heart failure (CHF) is a common condition with a poor prognosis. It is associated with poor exercise tolerance and debilitating symptoms. These symptoms appear to be associated with pathophysiological changes that occur systemically in the patient with CHF. Exercise training in carefully selected patients has been shown to be safe and to improve exercise capacity. Many of the pathophysiological abnormalities of CHF are improved by training. Some studies have suggested a possible improvement in morbidity and mortality with training. This review analyzes the controlled clinical trials of exercise training in CHF published to date.     

Spatial and temporal expression of histone demethylase,Kdm2a,during murine molar development

The histone demethylase, lysine (K)-specific demethylase 2A (Kdm2a), is highly conserved and expressed ubiquitously. Kdm2a can regulate cell proliferation and osteo/dentinogenic, adipogenic and chondrogenic differentiation of mesenchymal stem cells (MSCs) derived from dental tissue. We used quantitative real-time RT-PCR analysis and immunohistochemistry to detect Kdm2a expression during development of the murine molar at embryonic days E12, E14, E16 and E17 and postnatal days P3 and P14. Immunohistochemistry results showed no positive staining of Kdm2a at E12. At E14, Kdm2a was expressed weakly in the inner enamel epithelium, stellate reticulum cells and dental sac. At E16, Kdm2a was expressed mainly in the inner and outer enamel epithelium, stratum intermedium and dental sac, but weaker staining was found in cervical loop and dental papilla cells adjacent to the basement membrane. At E17, the strongest Kdm2a staining was detected in the ameloblasts and stronger Kdm2a staining also was detected in the stratum intermedium, outer enamel epithelium and dental papilla cells compared to the expression at E16. Postnatally, we found that Kdm2a was localized in secretory and mature ameloblasts and odontoblasts, and dentin was unstained. Real-time RT-PCR showed that Kdm2a mRNA levels in murine germ cells increased from E12 to E14 and from E14 to E16; no significant change occurred at E16, E17 or P3, then the levels decreased at P14 compared to P3. Kdm2a expression may be closely related to cell proliferation, to ameloblast and odontoblast differentiation and to the secretion of extracellular enamel and dentin during murine tooth development.     

Xanthan degragation by biofilm in porous media

Biological activity in oil reservoirs can cause significant problems such as souring and plugging. This study focuses on the problem of polymer degradation and permeability reduction due to biofilm formation during polymer injection for improved oil recovery. Polymers are included in injection fluids to increase their viscosity. Results relating biological processes and polymer degradation to fluid‐dynamic conditions in a laboratory model porous medium are presented.

A transparent flow cell with an etched two‐dimensional network of pores served as a model porous medium. A sterile xanthan polymer and natural sea water solution were continuously injected into the porous medium. A bacterial culture capable of xanthan degradation was introduced into the cell by a single injection. Some of the cells from this culture attached to the pore walls forming an immobile bacterial culture, termed biofilm. The development of this biofilm, its xanthan degradation and its effect on permeability were measured.

The effects of injection rate and rate transitions were analyzed. Injection fluid viscosity was reduced by 30% after 5 min flow through the porous medium at the maximum steady state degradation rate observed. Permeability was significantly reduced by the xanthan degrading biofilm, causing an increase in pressure drop through the porous medium of up to 80%. Polymer injection in oil reservoirs may, therefore, have negative effects on oil recovery, unless efficient biofouling control is applied. The methodology presented may serve as a tool in the development of biofouling control measures in porous media.     

Winter Active Bumblebees (Bombus terrestris) Achieve High Foraging Rates in Urban Britain

Background

Foraging bumblebees are normally associated with spring and summer in northern Europe. However, there have been sightings of the bumblebee Bombus terrestris during the warmer winters in recent years in southern England. But what floral resources are they relying upon during winter and how much winter forage can they collect?

Methodology/Principal Findings

To test if urban areas in the UK provide a rich foraging niche for bees we set up colonies of B. terrestris in the field during two late winter periods (2005/6 & 2006/7) in London, UK, and measured their foraging performance. Fully automatic radio-frequency identification (RFID) technology was used in 2006/7 to enable us to record the complete foraging activity of individually tagged bees. The number of bumblebees present during winter (October 2007 to March 2008) and the main plants they visited were also recorded during transect walks. Queens and workers were observed throughout the winter, suggesting a second generation of bee colonies active during the winter months. Mass flowering shrubs such as Mahonia spp. were identified as important food resources. The foraging experiments showed that bees active during the winter can attain nectar and pollen foraging rates that match, and even surpass, those recorded during summer.

Conclusions/Significance

B. terrestris in the UK are now able to utilise a rich winter foraging resource in urban parks and gardens that might at present still be under-exploited, opening up the possibility of further changes in pollinator phenology.     

Analysis of pollen and nectar of Arbutus unedo as a food source for Bombus terrestris (Hymenoptera: Apidae)

The mineral, total amino acid, and sterol compositions of pollen collected by Apis mellifera L. were compared with the pollen of a plant consumed by Bombus terrestris (L.): Arbutus unedo L. This plant provides the predominant food resource for the main autumn generation of B. terrestris in southern France. Honey bees also forage on this plant, although only for nectar. The mineral composition of 30 pollen samples collected by honey bees is close to the presently known requirements of A. mellifera, except for Cu and Mn, which are substantially lower. The total amino acid mean composition of a set of 54 pollen samples fits the basic requirements of honey bees except for valine, isoleucine, and methionine, which are present in lower concentrations in all the samples. For pollen of A. unedo, the amino acid balance is not very different from that of the survey. The main sterolic component in pollen of A. unedo, beta-sitosterol, is known to have antifeedant effects on A. mellifera. Honey bees cannot dealkylate C29 sterols like beta-sitosterol or delta5-avenasterol to obtain C27 cholesterol and ecdysteroids. Because these phytosterols as well as cholesterol are nearly absent from pollen of A. unedo, the metabolic capabilities of Apis seem unadapted to this plant. On the contrary, pollen of A. unedo is freely consumed by B. terrestris, which develops huge autumn populations solely on this food. These data indicate that the sterolic metabolisms of B. terrestris and A. mellifera differ, allowing separation in foraging activity.