mRNA and microRNA analysis reveals modulation of biochemical pathways related to addiction in the ventral tegmental area of methamphetamine self-administering rats.

BACKGROUND: Methamphetamine is a highly addictive central nervous system stimulant with increasing levels of abuse worldwide. Alterations to mRNA and miRNA expression within the mesolimbic system can affect addiction-like behaviors and thus play a role in the development of drug addiction. While many studies have investigated the effects of high-dose methamphetamine, and identified neurotoxic effects, few have looked at the role that persistent changes in gene regulation play following methamphetamine self-administration. Therefore, the aim of this study was to identify RNA changes in the ventral tegmental area following methamphetamine self-administration. We performed microarray analyses on RNA extracted from the ventral tegmental area of Sprague-Dawley rats following methamphetamine self-administration training (2 h/day) and 14 days of abstinence. RESULTS: We identified 78 miRNA and 150 mRNA transcripts that were differentially expressed (fdr adjusted p < 0.05, absolute log2 fold change >0.5); these included genes not previously associated with addiction (miR-125a-5p, miR-145 and Foxa1), loci encoding receptors related to drug addiction behaviors and genes with previously recognized roles in addiction such as miR-124, miR-181a, DAT and Ret. CONCLUSION: This study provides insight into the effects of methamphetamine on RNA expression in a key brain region associated with addiction, highlighting the possibility that persistent changes in the expression of genes with both known and previously unknown roles in addiction occur.

The Short Version of the Sequential Occupational Dexterity Assessment based on individual tasks' sensitivity to change.

OBJECTIVE: The Sequential Occupational Dexterity Assessment (SODA) is a reliable and valid instrument to measure bimanual hand function in rheumatoid arthritis. Since administering SODA is time-consuming, the aim of this study is to construct a short SODA (SODA-S). METHODS: Dexterity was measured with the SODA twice (with an interval of one year) in 94 patients. Item analyses based on the different SODA tasks were carried out to determine which of the 12 individual tasks were most responsible for the observed changes in dexterity. RESULTS: Six of the 12 SODA tasks were identified as sensitive to change. Based on these 6 tasks, the SODA-S was computed. Internal consistency of the SODA-S is good (Cronbach's alphas at baseline and followup were 0.82 and 0.85, respectively). The correlation between the SODA and SODA-S is 0.92. This means that the information gathered from the SODA-S is almost equal to the information gathered from the full SODA. Norm scores are provided for both instruments. CONCLUSION: The SODA-S is a good alternative to the full SODA in following patient's dexterity in daily practice. However, when evaluating the effect of specific hand treatment, the full SODA may be preferred.

Remarkably similar response to gold therapy in HLA identical sibs with rheumatoid arthritis.

Two pairs of sibs with definite rheumatoid arthritis responded in a remarkably similar way to parenteral gold therapy, in terms of both toxicity and efficacy. Both pairs proved to be HLA identical. One of the pairs possessed the HLA antigens B8 and DR3, which have been associated with both drug toxicity and excellent clinical response. The other pair did not possess either of these antigens, suggesting that the reaction to gold therapy in patients with rheumatoid arthritis may be determined by other HLA or genetic factors coded for by chromosome 6, or both.

Radiosynoviorthesis in haemophilic joint disease.

The effects of radiosynoviorthesis on chronic haemophilic arthropathic joints were studied in six patients with severe haemophilia by a follow up study which spanned two and a half years. On clinical grounds the treatment was successful because pain and bleeding frequency diminished, although radiographic examination showed further deterioration of the treated joint. Chromosome damage was not detected. We conclude that radiosynoviorthesis is apparently changing the bleeding pattern of articular tissues without arresting the destruction and deformation of joints.