Drug and Alcohol Rehabilitation: Liver Dysfunction and Phosphatidylinositol-3-Kinase Signalling in Early Sepsis: Experimental Studies in Rodent Models of Peritonitis.

Liver dysfunction and phosphatidylinositol-3-kinase signalling in early sepsis: experimental studies in rodent models of peritonitis.

Filed under: Drug and Alcohol Rehabilitation

PLoS Med. 2012 Nov; 9(11): e1001338
Recknagel P, Gonnert FA, Westermann M, Lambeck S, Lupp A, Rudiger A, Dyson A, Carré JE, Kortgen A, Krafft C, Popp J, Sponholz C, Fuhrmann V, Hilger I, Claus RA, Riedemann NC, Wetzker R, Singer M, Trauner M, Bauer M

Hepatic dysfunction and jaundice are traditionally viewed as late features of sepsis and portend poor outcomes. We hypothesized that changes in liver function occur early in the onset of sepsis, yet pass undetected by standard laboratory tests.In a long-term rat model of faecal peritonitis, biotransformation and hepatobiliary transport were impaired, depending on subsequent disease severity, as early as 6 h after peritoneal contamination. Phosphatidylinositol-3-kinase (PI3K) signalling was simultaneously induced at this time point. At 15 h there was hepatocellular accumulation of bilirubin, bile acids, and xenobiotics, with disturbed bile acid conjugation and drug metabolism. Cholestasis was preceded by disruption of the bile acid and organic anion transport machinery at the canalicular pole. Inhibitors of PI3K partially prevented cytokine-induced loss of villi in cultured HepG2 cells. Notably, mice lacking the PI3K? gene were protected against cholestasis and impaired bile acid conjugation. This was partially confirmed by an increase in plasma bile acids (e.g., chenodeoxycholic acid [CDCA] and taurodeoxycholic acid [TDCA]) observed in 48 patients on the day severe sepsis was diagnosed; unlike bilirubin (area under the receiver-operating curve: 0.59), these bile acids predicted 28-d mortality with high sensitivity and specificity (area under the receiver-operating curve: CDCA: 0.77; TDCA: 0.72; CDCA+TDCA: 0.87).Liver dysfunction is an early and commonplace event in the rat model of sepsis studied here; PI3K signalling seems to play a crucial role. All aspects of hepatic biotransformation are affected, with severity relating to subsequent prognosis. Detected changes significantly precede conventional markers and are reflected by early alterations in plasma bile acids. These observations carry important implications for the diagnosis of liver dysfunction and pharmacotherapy in the critically ill. Further clinical work is necessary to extend these concepts into clinical practice. Please see later in the article for the Editors’ Summary.
HubMed – drug

Mometasone implant for chronic rhinosinusitis.

Filed under: Drug and Alcohol Rehabilitation

Med Devices (Auckl). 2012; 5: 75-80
Wei CC, Kennedy DW

The Propel mometasone-eluting stent (Intersect ENT, Palo Alto, CA) is the first Food and Drug Administration-approved device for delivering steroid medication into the ethmoid cavity following surgery. The implant is composed of a biodegradable polymer in a lattice pattern that expands in a spring-like fashion to conform to the walls of a dissected ethmoid cavity and contains a total of 370 ?g of mometasone furoate designed for gradual release over 30 days. The purpose of this article is to review the mode of action and the evidence supporting the efficacy of this novel technology. Three recently published clinical trials have demonstrated that the mometasone-eluting stent produced statistically significant reductions in inflammation, polyp formation, and postoperative adhesions. In addition, the implant has been found to significantly reduce the need for postoperative administration of oral steroids and to decrease the frequency of postoperative lysis of adhesions. Minimal adverse effects were reported in these trials and included infection, crusting, and granulation tissue formation. Although the placement of steroid-impregnated packing, stents, sponges, and gels has previously been used in the postoperative sinus cavities, the Propel mometasone-eluting stent introduces a new mechanism for localized and controlled delivery of topical therapy directly to the nasal mucosa for chronic rhinosinusitis.
HubMed – drug

RX Herculink Elite(®) renal stent system: a review of its use for the treatment of renal artery stenosis.

Filed under: Drug and Alcohol Rehabilitation

Med Devices (Auckl). 2012; 5: 67-73
Colyer WR

The management of renal artery stenosis (RAS) remains controversial. While some evidence suggests that treatment with stent placement is beneficial, randomized trials have failed to demonstrate a significant benefit. Ongoing clinical trials should help to better define the role for stenting of RAS while avoiding limitations seen with earlier trials. When it comes to stenting for RAS, several stents have been used; however, many stents which have been used previously and which are still being used are biliary stents that are used “off-label.” These stents have typically come onto the market through the 510(k) pathway. To date, a total of five stents have been approved by the United States Food and Drug Administration for use in the renal arteries. Of the five stents that have received approval, the Bridge™ Extra Support (Medtronic Cardio- Vascular, Santa Rosa, CA) and the Palmaz(®) (Cordis Corporation, Bridgewater, NJ) stents are no longer available. Currently, the Express(®) SD (Boston Scientific, Natick, MA), Formula™ (Cook Medical, Bloomington, IN), and Herculink Elite(®) (Abbott Vascular, Santa Clara, CA) stents are Food and Drug Administration approved and available for use. The Herculink Elite is the most recently approved of the renal stents, having received approval in late 2011. The Herculink Elite stent is the only cobalt chromium stent approved for use in the renal arteries. Although trial data are limited and direct comparisons among renal stents is not possible, the Herculink Elite stent has demonstrated good performance. Additionally, the design of the Herculink Elite offers some advantages that may translate into improved outcomes.
HubMed – drug

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