Addiction Rehab: Regulation of BDNF Expression by Cocaine.

Regulation of BDNF expression by cocaine.

Filed under: Addiction Rehab

Yale J Biol Med. 2012 Dec; 85(4): 437-46
McCarthy DM, Brown AN, Bhide PG

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. It is expressed throughout the nervous system. A unique feature of the BDNF gene is the existence of multiple mRNA transcripts, all of which are translated into BDNF protein, suggesting a multilevel regulation of expression. In particular, the BDNF exon IV promoter region is a preferential target for epigenetic alterations, as it contains binding sites for CREB and MeCP2, two transcriptional regulators known to mediate epigenetic changes. Exposure to drugs of abuse is known to modulate epigenetic regulation of BDNF gene expression. This review will discuss how exposure to cocaine, one of the most addictive drugs known to mankind, can produce alterations in BDNF gene expression, especially in the mesolimbic dopaminergic system, which lead to alterations in the reward-mediated behaviors involved in addiction.
HubMed – addiction

Targeting late SV40 factor: Is the achilles heel of hepatocarcinogenesis revealed?

Filed under: Addiction Rehab

World J Gastroenterol. 2012 Dec 14; 18(46): 6709-11
Shlomai A

Hepatocellular carcinoma (HCC) is a dreadful cancer and a major cause of death among patients with chronic liver disease and cirrhosis. The apparent alterations in a diversity of intracellular pathways found in HCC has set the rational for developing molecular-directed drugs that simultaneously inhibit multiple pathways, such as the multi-kinase inhibitor Sorafenib. However, recently this concept has been challenged by showing that HCC is heavily dependent on a single oncogene designated late SV-40 factor (LSF), a transcription factor that is over-expressed in liver cancer cells and that its expression is strongly correlated with tumor grade and aggressiveness. Furthermore, using an intensive screening for drugs that inhibit LSF activity, Grant et al have found a molecule designated factor quinolinone inhibitor 1 that can specifically block the ability of LSF to bind its target promoters, resulting in a massive death of HCC cells both in vitro and in vivo. The innovative findings of HCC representing “oncogene addiction” to LSF and the ability of a single molecule to block the activity of this oncogene resulting in tumor abolishment are encouraging and provide us with the hope that the “Achilles heel” of HCC has been found.
HubMed – addiction

Race, Gender, and Nicotine Metabolism in Adolescent Smokers.

Filed under: Addiction Rehab

Nicotine Tob Res. 2012 Dec 13;
Rubinstein ML, Shiffman S, Rait MA, Benowitz NL

INTRODUCTION: Differences in the rate of nicotine metabolism between genders and different races have been hypothesized to contribute to disparities in smoking rate, susceptibility to addiction, and ability to quit smoking. The purpose of this study was to determine the effect of race and gender on the rate of nicotine metabolism as indicated by the nicotine metabolite ratio (NMR) in adolescent smokers. METHODS: One hundred and fifty-nine adolescent smokers aged 13-17 were given 2mg of deuterium-labeled cotinine (cotinine-d(4)). The NMR was calculated as the ratio of concentrations of deuterium-labeled 3′-hydroxycotinine (ng/ml) to cotinine-d(4) (ng/ml) in saliva and is a validated biomarker of the rate of nicotine metabolism. RESULTS: The sample was 67.3% female and racially mixed. On average, Whites had the fastest rates of metabolism compared with both Blacks/African Americans (p < .01) and Asians (p = .01). The NMR was similar between males and females (p = .70). Among the 19 girls who reported using estrogen-containing contraceptives, there was no significant difference in NMR compared with the 83 girls who did not use contraceptives (p = .24) or the 10 who used progestin-only contraceptives (p = .45). CONCLUSIONS: Among adolescent smokers, racial variations in rates of nicotine metabolism were similar to those that have been reported in adult smokers. In contrast to findings in adult smokers, the NMR did not vary significantly by gender or self-reported hormone use. HubMed – addiction

Addiction ruined my life.. – Footage from John’s Walk for Recovery – A fundraiser for the documentary “The Choosing” An independent film about addiction and recovery. Produced by White Light Productions Minnesota. Can anyone recover form addiction? Executive Producer John Overby Produced by Eric Rech Camera A John Overby Camera B Jay Smiley Edited by Chris Bueckers

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