Inhibition of Heme Peroxidases by Melamine.
Inhibition of Heme Peroxidases by Melamine.
Filed under: Drug and Alcohol Rehabilitation
Enzyme Res. 2012; 2012: 416062
Vanachayangkul P, Tolleson WH
In 2008 melamine-contaminated infant formula and dairy products in China led to over 50,000 hospitalizations of children due to renal injuries. In North America during 2007 and in Asia during 2004, melamine-contaminated pet food products resulted in numerous pet deaths due to renal failure. Animal studies have confirmed the potent renal toxicity of melamine combined with cyanuric acid. We showed previously that the solubility of melamine cyanurate is low at physiologic pH and ionic strength, provoking us to speculate how toxic levels of these compounds could be transported through the circulation without crystallizing until passing into the renal filtrate. We hypothesized that melamine might be sequestered by heme proteins, which could interfere with heme enzyme activity. Four heme peroxidase enzymes were selected for study: horseradish peroxidase (HRP), lactoperoxidase (LPO), and cyclooxygenase-1 and -2 (COX-1 and -2). Melamine exhibited noncompetitive inhibition of HRP (K(i)??9.5 ± 0.7?mM), and LPO showed a mixed model of inhibition (K(i)??14.5 ± 4.7?mM). The inhibition of HRP and LPO was confirmed using a chemiluminescent peroxidase assay. Melamine also exhibited COX-1 inhibition, but inhibition of COX-2 was not detected. Thus, our results demonstrate that melamine inhibits the activity of three heme peroxidases.
HubMed – drug
Abiraterone and other novel androgen-directed strategies for the treatment of prostate cancer: a new era of hormonal therapies is born.
Filed under: Drug and Alcohol Rehabilitation
Ther Adv Urol. 2012 Aug; 4(4): 167-78
Schweizer MT, Antonarakis ES
The number of life-prolonging therapies proven effective in the treatment of metastatic castrate-resistant prostate cancer (CRPC) has been limited until recently. In the past 2 years several such therapies have come to market. In 2010, the autologous immunotherapy sipuleucel-T and the next-generation taxane cabazitaxel were approved in this setting. However, abundant evidence has shown that CRPC growth continues to be driven through androgen-dependent signaling. Both of these drugs fail to take advantage of this targetable oncogenic pathway. Potent specific inhibitors of cytochrome P450-17 have been engineered with the aim of suppressing androgen synthesis beyond that seen with the luteinizing hormone-releasing hormone agonists/antagonists. Abiraterone acetate was developed by rational design based on a pregnenolone parent structure. Its approval by the US Food and Drug Administration (FDA) was granted in 2011 based on phase III data demonstrating an overall survival advantage compared with placebo. More recently, other drugs that act along the androgen signaling pathway, such as orteronel (TAK-700), galeterone (TOK-001), enzalutamide (MDV3100) and ARN-509, have shown promise in clinical trials. Some of these are expected to gain FDA approval in the near future. Here, we review abiraterone and other novel androgen-directed therapeutic strategies for the management of advanced prostate cancer.
HubMed – drug
Are probiotics effective in management of irritable bowel syndrome?
Filed under: Drug and Alcohol Rehabilitation
Arch Med Sci. 2012 Jul 4; 8(3): 403-5
Hosseini A, Nikfar S, Abdollahi M
Ex-Lions receiver Charles Rogers free from custody, says judge saved his life
Filed under: Drug and Alcohol Rehabilitation
Former Detroit Lions and Michigan State receiver Charles Rogers has completed a drug and alcohol rehabilitation program while his trial on five misdemeanors has been postponed. Rogers, also a former Saginaw High football star, was in Saginaw County …
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