Bilirubin decreases NOS2 expression via inhibition of NAD(P)H oxidase: implications for protection against endotoxic shock in rats.

We investigated a possible beneficial role for bilirubin, one of the products of heme degradation by the cytoprotective enzyme heme oxygenase-1 in counteracting Escherichia coli endotoxin-mediated toxicity. Homozygous jaundice Gunn rats, which display high plasma bilirubin levels due to deficiency of glucuronyl transferase activity, and Sprague-Dawley rats subjected to sustained exogenous bilirubin administration were more resistant to endotoxin (LPS)-induced hypotension and death compared with nonhyperbilirubinemic rats. LPS-stimulated production of nitric oxide (NO) was significantly decreased in hyperbilirubinemic rats compared with normal animals; this effect was associated with reduction of inducible NO synthase (NOS2) expression in renal, myocardial, and aortic tissues. Furthermore, NOS2 protein expression and activity were reduced in murine macrophages stimulated with LPS and preincubated with bilirubin at concentrations similar to that found in the serum of hyperbilirubinemic animals. This effect was secondary to inhibition of NAD(P)H oxidase since 1) inhibition of NAD(P)H oxidase attenuated NOS2 induction by LPS, 2) bilirubin decreased NAD(P)H oxidase activity in vivo and in vitro, and 3) down-regulation of NOS2 by bilirubin was reversed by addition of NAD(P)H. These findings indicate that bilirubin can act as an effective agent to reduce mortality and counteract hypotension elicited by endotoxin through mechanisms involving a decreased NOS2 induction secondary to inhibition of NAD(P)H oxidase

Inhibition of T-type calcium channels protects neurons from delayed ischemia-induced damage.Mol

Abstract: 174 words Introduction: 536 word

CC9 Livestock-Associated Staphylococcus aureus Emerges in Bloodstream Infections in French Patients Unconnected With Animal Farming

We report 4 bloodstream infections associated with CC9 agr type II Staphylococcus aureus in individuals without animal exposure. We demonstrate, by microarray analysis, the presence of egc cluster, fnbA, cap operon, lukS, set2, set12, splE, splD, sak, epiD, and can, genomic features associated with a high virulence potential in human

The epithelial cholinergic system of the airways

Acetylcholine (ACh), a classical transmitter of parasympathetic nerve fibres in the airways, is also synthesized by a large number of non-neuronal cells, including airway surface epithelial cells. Strongest expression of cholinergic traits is observed in neuroendocrine and brush cells but other epithelial cell types—ciliated, basal and secretory—are cholinergic as well. There is cell type-specific expression of the molecular pathways of ACh release, including both the vesicular storage and exocytotic release known from neurons, and transmembrane release from the cytosol via organic cation transporters. The subcellular distribution of the ACh release machineries suggests luminal release from ciliated and secretory cells, and basolateral release from neuroendocrine cells. The scenario as known so far strongly suggests a local auto-/paracrine role of epithelial ACh in regulating various aspects on the innate mucosal defence mechanisms, including mucociliary clearance, regulation of macrophage function and modulation of sensory nerve fibre activity. The proliferative effects of ACh gain importance in recently identified ACh receptor disorders conferring susceptibility to lung cancer. The cell type-specific molecular diversity of the epithelial ACh synthesis and release machinery implies that it is differently regulated than neuronal ACh release and can be specifically targeted by appropriate drugs

The relation between excretory rhythm and water content of honeydew from Cinara pectinatae Nördl and Cinara pilicornis (Hartig) and the honeydew harvesting activity of the honeybee, Apis mellifica L

Preliminary observations of Cinara pectinatae honeydew harvesting by honey bees show that honeydew harvesting activity varies throughout the day. The honeydew excretion activity of Cinara pectinatae and Cinara pilicornis was studied using a revolving plate that allowed honeydew droplets excreted in 24 h to be counted. Maximum excretion occurs between 20 00 and 24 00 h and a minimum excretion between 12 00 and 15 00 in C pectinatae (fig 1A). In C pilicornis there does not appear to be a circadian rhythm of honeydew excretion (fig 1 B). Refractometer measurements of the proportion of honeydew dry matter show that the dry matter content of freshly excreted honeydew varies between 52% and 78%. We also found a negative correlation between the relative hygrometry and the honeydew dry matter content (fig 2). It was noted that dry matter content increases during the morning until 12 00 h, is stable during the early afternoon at a high value and decreases after 16 00 h (fig 3). The study of honeydew harvesting activity shows that honey bees collect honeydew at a high level from 10 00-11 00 h during warm and dry weather (fig 3 a, b, c, d, f) and from 12 00-14 00 h during raw weather (fig 3 g, h). Thus, the drying of the honeydew during the day and the honeydew excretion rhythm are 2 factors which apparently limit the harvesting of honeydew by the honey bee