BIOMARKERS of OPERATIONAL TOLERANCE in SOLID ORGAN TRANSPLANTATION.
BIOMARKERS OF OPERATIONAL TOLERANCE IN SOLID ORGAN TRANSPLANTATION.
Filed under: Drug and Alcohol Rehabilitation
Expert Opin Med Diagn. 2012 Jul; 6(4): 281-293
Heidt S, Wood KJ
INTRODUCTION: Long-term immunosuppressive therapy represents a huge burden on transplant recipients, but currently cannot be omitted. Improving long-term transplant outcome by immunosuppressive drug withdrawal may be achieved in patients who have developed (partial) immunological unresponsiveness towards their graft, either spontaneously or through tolerance induction. Reliable biomarkers are essential to define such immunological unresponsiveness and will facilitate controlled immunosuppressive drug weaning as well as provide surrogate end-points for tolerance induction trials. AREAS COVERED: Tolerance biomarkers have been defined for both liver and kidney transplantation and can accurately identify operationally tolerant transplant recipients retrospectively. These two tolerance fingerprints are remarkably different, indicating the involvement of distinct mechanisms. Limited data suggest that tolerance biomarkers can be detected in immunosuppressed transplant recipients. Whether these patients can safely have their immunosuppressive drugs withdrawn needs to be established. EXPERT OPINION: Mechanistic interpretation of the kidney transplant tolerance biomarker profile dominated by B cell markers remains a challenge in light of experimental evidence suggesting the pivotal involvement of regulatory T cells. Therefore, defining animal models that resemble human transplant tolerance is crucial in understanding the underlying mechanisms. Additionally, to ensure patient safety while monitoring for tolerance, it is essential to develop biomarkers to non-invasively detect early signs of rejection as well.
HubMed – drug
Evaluation of chinese-herbal-medicine-induced herb-drug interactions: focusing on organic anion transporter 1.
Filed under: Drug and Alcohol Rehabilitation
Evid Based Complement Alternat Med. 2012; 2012: 967182
Lin CC, Fan HY, Kuo CW, Pao LH
The consumption of Chinese herbal medicines (CHMs) is increasing exponentially. Many patients utilize CHMs concomitantly with prescription drugs in great frequency. Herb-drug interaction has hence become an important focus of study. Transporter-mediated herb-drug interactions have the potential to seriously influence drug efficacy and toxicity. Since organic anion transporter 1 (OAT1) is crucial in renal active secretion and drug-drug interactions, the possibility of modulation of OAT1-mediated drug transport should be seriously concerned. Sixty-three clinically used CHMs were evaluated in the study. An hOAT1-overexpressing cell line was used for the in vitro CHMs screening, and the effective candidates were administered to Wistar rats to access renal hemodynamics. The regulation of OAT1 mRNA expression was also examined for further evidence of CHMs affecting OAT1-mediated transport. Among all the 63?CHMs, formulae Gui Zhi Fu Ling Wan (GZ) and Chia Wei Hsiao Yao San (CW) exhibited significant inhibitions on hOAT1-mediated [(3)H]-PAH uptake in vitro and PAH clearance and net secretion in vivo. Moreover, GZ showed concentration-dependent manners both in vitro and in vivo, and the decrease of rOAT1 mRNA expression indicated that GZ not only inhibited function of OAT1 but also suppressed expression of OAT1.
HubMed – drug
Alkaloids isolated from natural herbs as the anticancer agents.
Filed under: Drug and Alcohol Rehabilitation
Evid Based Complement Alternat Med. 2012; 2012: 485042
Lu JJ, Bao JL, Chen XP, Huang M, Wang YT
Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made.
HubMed – drug
Management of peptic ulcer bleeding in different case volume workplaces: results of a nationwide inquiry in hungary.
Filed under: Drug and Alcohol Rehabilitation
Gastroenterol Res Pract. 2012; 2012: 956434
Rácz I, Kárász T, Lukács K, Rácz F, Kersák J, Wacha J, Szalóki T, Szász M, Gyenes I, Altorjay I
The aim of this study was to conduct a national survey to evaluate the recent endoscopic treatment and drug therapy of peptic ulcer bleeding (PUB) patients and to compare practices in high and low case volume Hungarian workplaces. A total of 62 gastroenterology units participated in the six-month study. A total of 3033 PUB cases and a mean of 8.15 ± 3.9 PUB cases per month per unit were reported. In the 23 high case volume units (HCV), there was a mean of 12.9 ± 5.4 PUB cases/month, whereas in the 39 low case volume units (LCV), a mean of 5.3 ± 2.9 PUB cases/month were treated during the study period. In HCV units, endoscopic therapies for Forrest Ia, Ib, and IIa ulcers were significantly more often used than in LCV units (86% versus 68%; P = 0.001). Among patients with stigmata of recent haemorrhage (Forrest I, II), bolus + continuous infusion PPI was given significantly more frequently in HCV than in LCV units (49.6% versus 33.2%; P = 0.001). Mortality in HCV units was less than in LCV units (2.7% versus 4.3%; P = 0.023). The penetration of evidence-based recommendations for PUB management is stronger in HCV units resulting lower mortality.
HubMed – drug
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