Drug and Alcohol Rehabilitation: Inhibition of Mammalian Target of Rapamycin in Human Acute Myeloid Leukemia Cells Has Diverse Effects That Depend on the Environmental in Vitro Stress.
Inhibition of Mammalian target of rapamycin in human acute myeloid leukemia cells has diverse effects that depend on the environmental in vitro stress.
Filed under: Drug and Alcohol Rehabilitation
Bone Marrow Res. 2012; 2012: 329061
Ryningen A, Reikvam H, Nepstad I, Paulsen Rye K, Bruserud O
Effects of the mTOR inhibitor rapamycin were characterized on in vitro cultured primary human acute myeloid leukemia (AML) cells and five AML cell lines. Constitutive mTOR activation seemed to be a general characteristic of primary AML cells. Increased cellular stress induced by serum deprivation increased both mTOR signaling, lysosomal acidity, and in vitro apoptosis, where lysosomal acidity/apoptosis were independent of increased mTOR signaling. Rapamycin had antiproliferative and proapoptotic effects only for a subset of patients. Proapoptotic effect was detected for AML cell lines only in the presence of serum. Combination of rapamycin with valproic acid, all-trans retinoic acid (ATRA), and NF-?B inhibitors showed no interference with constitutive mTOR activation and mTOR inhibitory effect of rapamycin and no additional proapoptotic effect compared to rapamycin alone. In contrast, dual inhibition of the PI3K-Akt-mTOR pathway by rapamycin plus a PI3K inhibitor induced new functional effects that did not simply reflect a summary of single drug effects. To conclude, (i) pharmacological characterization of PI3K-Akt-mTOR inhibitors requires carefully standardized experimental models, (ii) rapamycin effects differ between patients, and (iii) combined targeting of different steps in this pathway should be further investigated whereas combination of rapamycin with valproic acid, ATRA, or NF-?B inhibitors seems less promising.
HubMed – drug
Pharmacogenetic study of drug-metabolising enzyme polymorphisms on the risk of anti-tuberculosis drug-induced liver injury: a meta-analysis.
Filed under: Drug and Alcohol Rehabilitation
PLoS One. 2012; 7(10): e47769
Cai Y, Yi J, Zhou C, Shen X
Three first-line antituberculosis drugs, isoniazid, rifampicin and pyrazinamide, may induce liver injury, especially isoniazid. This antituberculosis drug-induced liver injury (ATLI) ranges from a mild to severe form, and the associated mortality cases are not rare. In the past decade, many investigations have focused the association between drug-metabolising enzyme (DME) gene polymorphisms and risk for ATLI; however, these studies have yielded contradictory results.PubMed, EMBASE, ISI web of science and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between polymorphisms from 4 DME genes (NAT2, CYP2E1, GSTM1 and GSTT1) and susceptibility to ATLI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Heterogeneity among articles and their publication bias were also tested.38 studies involving 2,225 patients and 4,906 controls were included. Overall, significantly increased ATLI risk was associated with slow NAT2 genotype and GSTM1 null genotype when all studies were pooled into the meta-analysis. Significantly increased risk was also found for CYP2E1*1A in East Asians when stratified by ethnicity. However, no significant results were observed for GSTT1.Our results demonstrated that slow NAT2 genotype, CYP2E1*1A and GSTM1 null have a modest effect on genetic susceptibility to ATLI.
HubMed – drug
Pseudomonas aeruginosa Keratitis in Mice: Effects of Topical Bacteriophage KPP12 Administration.
Filed under: Drug and Alcohol Rehabilitation
PLoS One. 2012; 7(10): e47742
Fukuda K, Ishida W, Uchiyama J, Rashel M, Kato S, Morita T, Muraoka A, Sumi T, Matsuzaki S, Daibata M, Fukushima A
The therapeutic effects of bacteriophage (phage) KPP12 in Pseudomonas aeruginosa keratitis were investigated in mice. Morphological analysis showed that phage KPP12 is a member of the family Myoviridae, morphotype A1, and DNA sequence analysis revealed that phage KPP12 is similar to PB1-like viruses. Analysis of the phage KPP12 genome did not identify any genes related to drug resistance, pathogenicity or lysogenicity, and so phage KPP12 may be a good candidate for therapeutic. KPP12 showed a broad host range for P. aeruginosa strains isolated from clinical ophthalmic infections. Inoculation of the scarified cornea with P. aeruginosa caused severe keratitis and eventual corneal perforation. Subsequent single-dose administration of KPP12 eye-drops significantly improved disease outcome, and preserved the structural integrity and transparency of the infected cornea. KPP12 treatment resulted in the suppression of neutrophil infiltration and greatly enhanced bacterial clearance in the infected cornea. These results indicate that bacteriophage eye-drops may be a novel adjunctive or alternative therapeutic agent for the treatment of infectious keratitis secondary to antibiotic-resistant bacteria.
HubMed – drug
Antimicrobial Resistance and Spread of Multi Drug Resistant Escherichia coli Isolates Collected from Nine Urology Services in the Euregion Meuse-Rhine.
Filed under: Drug and Alcohol Rehabilitation
PLoS One. 2012; 7(10): e47707
van der Donk CF, van de Bovenkamp JH, De Brauwer EI, De Mol P, Feldhoff KH, Kalka-Moll WM, Nys S, Thoelen I, Trienekens TA, Stobberingh EE
We determined the prevalence and spread of antibiotic resistance and the characteristics of ESBL producing and/or multi drug resistant (MDR) Escherichia coli isolates collected from urine samples from urology services in the Euregio Meuse-Rhine, the border region of the Netherlands (n?=?176), Belgium (n?=?126) and Germay (n?=?119). Significant differences in resistance between the three regions were observed. Amoxicillin-clavulanic acid resistance ranged from 24% in the Netherlands to 39% in Belgium (p?=?0.018), from 20% to 40% (p<0.004) for the fluoroquinolones and from 20% to 40% (p?=?0.018) for the folate antagonists. Resistance to nitrofurantoin was less than 5%. The prevalence of ESBL producing isolates varied from 2% among the Dutch isolates to 8% among the German ones (p?=?0.012) and were mainly CTX-M 15. The prevalence of MDR isolates among the Dutch, German and Belgian isolates was 11%, 17% and 27%, respectively (pHubMed – drug
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