Drug and Alcohol Rehabilitation: Reconstruction of Sugar Metabolic Pathways of Giardia Lamblia.

Reconstruction of Sugar Metabolic Pathways of Giardia lamblia.

Filed under: Drug and Alcohol Rehabilitation

Int J Proteomics. 2012; 2012: 980829
Han J, Collins LJ

Giardia lamblia is an “important” pathogen of humans, but as a diplomonad excavate it is evolutionarily distant from other eukaryotes and relatively little is known about its core metabolic pathways. KEGG, the widely referenced site for providing information of metabolism, does not yet include many enzymes from Giardia species. Here we identify Giardia’s core sugar metabolism using standard bioinformatic approaches. By comparing Giardia proteomes with known enzymes from other species, we have identified enzymes in the glycolysis pathway, as well as some enzymes involved in the TCA cycle and oxidative phosphorylation. However, the majority of enzymes from the latter two pathways were not identifiable, indicating the likely absence of these functionalities. We have also found enzymes from the Giardia glycolysis pathway that appear more similar to those from bacteria. Because these enzymes are different from those found in mammals, the host organisms for Giardia, we raise the possibility that these bacteria-like enzymes could be novel drug targets for treating Giardia infections.
HubMed – drug


The Critical Role of Redox Homeostasis in Shikonin-Induced HL-60 Cell Differentiation via Unique Modulation of the Nrf2/ARE Pathway.

Filed under: Drug and Alcohol Rehabilitation

Oxid Med Cell Longev. 2012; 2012: 781516
Zhang B, Chen N, Chen H, Wang Z, Zheng Q

Among various cancer cell lines, the leukemia cell line HL-60 was most sensitive to Shikonin, with evidence showing both the prooxidative activities and proapoptotic effects of micromolar concentrations of Shikonin. However, the mechanism involved in the cytotoxicity of Shikonin in the submicromolar range has not been fully characterized. Using biochemical and free radical biological experiments in vitro, we identified the prodifferentiated profiles of Shikonin and evaluated the redox homeostasis during HL-60 differentiation. The data showed a strong dose-response relationship between Shikonin exposure and the characteristics of HL-60 differentiation in terms of morphology changes, nitroblue tetrazolium (NBT) reductive activity, and the expression level of surface antigens CD11b/CD14. During drug exposure, intercellular redox homeostasis changes towards oxidation are necessary to support Shikonin-induced differentiation, which was proven by additional enzymatic and non-enzymatic redox modulators. A statistically significant and dose-dependent increase (P < 0.05) was recorded with regard to the unique expression levels of the Nrf2/ARE downstream target genes in HL-60 cells undergoing late differentiation, which were restored with further antioxidants employed with the Shikonin treatment. Our research demonstrated that Shikonin is a differentiation-inducing agent, and its mechanisms involve the Nrf2/ARE pathway to modulate the intercellular redox homeostasis, thus facilitating differentiation. HubMed – drug


The protection of acetylcholinesterase inhibitor on ?-amyloid-induced the injury of neurite outgrowth via regulating axon guidance related genes expression in neuronal cells.

Filed under: Drug and Alcohol Rehabilitation

Int J Clin Exp Pathol. 2012; 5(9): 900-13
Shen JN, Wang DS, Wang R

Cognitive deficits in AD correlate with progressive synaptic dysfunction and loss. The Rho family of small GTPases, including Rho, Rac, and Cdc42, has a central role in cellular motility and cytokinesis. Acetylcholinesterase inhibitor has been found to protect cells against a broad range of reagents-induced injuries. Present studies examined if the effect of HupA on neurite outgrowth in A?-treated neuronal cells executed via regulating Rho-GTPase mediated axon guidance relative gene expression. Affymetrix cDNA microarray assay followed by real-time RT-PCR and Western Blotting analysis were used to elucidate and analyze the signaling pathway involved in A? and HupA’s effects. The effects of A? and HupA on the neurite outgrowth were further confirmed via immunofluorescence staining. A? up-regulated the mRNA expressions of NFAT5, LIMK1, EPHA1, NTN4 and RAC2 markedly in SH-SY5Y cells. Co-incubation of A? and HupA reversed or decreased the changes of NFAT5, NTN4, RAC2, CDC42 and SEMA4F. HupA treated alone increased NFAT5, LIMK1, NTN4 significantly. Following qRT-PCR validation showed that the correlation of the gene expression ratio between microarray and qRT-PCR is significant. Western blot result showed that the change of CDC42 protein is consistent with the mRNA level while RAC2 is not. The morphological results confirmed that HupA improved, or partly reversed, the A?-induced damage of neurite outgrowth. The protective effect of HupA from A? induced morphological injury might be correlative to, at least partially, regulating the network of neurite outgrowth related genes.
HubMed – drug


Variants Identified in a GWAS Meta-Analysis for Blood Lipids Are Associated with the Lipid Response to Fenofibrate.

Filed under: Drug and Alcohol Rehabilitation

PLoS One. 2012; 7(10): e48663
Aslibekyan S, Goodarzi MO, Frazier-Wood AC, Yan X, Irvin MR, Kim E, Tiwari HK, Guo X, Straka RJ, Taylor KD, Tsai MY, Hopkins PN, Korenman SG, Borecki IB, Chen YD, Ordovas JM, Rotter JI, Arnett DK

A recent large-scale meta-analysis of genome-wide studies has identified 95 loci, 59 of them novel, as statistically significant predictors of blood lipid traits; we tested whether the same loci explain the observed heterogeneity in response to lipid-lowering therapy with fenofibrate. Using data from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n?=?861) we fit linear mixed models with the genetic markers as predictors and high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol, and triglyceride concentrations as outcomes. For all four traits, we analyzed both baseline levels and changes in response to treatment with fenofibrate. For the markers that were significantly associated with fenofibrate response, we fit additional models evaluating potential epistatic interactions. All models were adjusted for age, sex, and study center as fixed effects, and pedigree as a random effect. Statistically significant associations were observed between the rs964184 polymorphism near APOA1 (P-value?0.0001) and fenofibrate response for HDL and triglycerides. The association was replicated in the Pharmacogenetics of Hypertriglyceridemia in Hispanics study (HyperTG, n?=?267). Suggestive associations with fenofibrate response were observed for markers in or near PDE3A, MOSC1, FLJ36070, CETP, the APOE-APOC1-APOC4-APOC2, and CILP2. Finally, we present strong evidence for epistasis (P-value for interaction?=? 0.0006 in GOLDN, 0.05 in HyperTG) between rs10401969 near CILP2 and rs4420638 in the APOE-APOC1-APOC4-APOC2 cluster with total cholesterol response to fenofibrate. In conclusion, we present evidence linking several novel and biologically relevant genetic polymorphisms to lipid lowering drug response, as well as suggesting novel gene-gene interactions in fenofibrate pharmacogenetics.
HubMed – drug



The Queen Knew Not to Shake Hands with the Chabad Shaliach – London – Rabbi Aryeh Sofrin was anxious just like the scores of other people scheduled to meet the Queen of England, but for a different reason: what would he do if she reached out for a handshake? The Chabad shaliach to Ilford, Essex, located northeast of London, was about to be dubbed Member of the British Empire for 18 years of work as head of a drug and alcohol rehabilitation center that serves Jews, Christians and Muslims and even has an imam on the staff. He had been briefed on proper protocol, but did not know what to do about the handshake that ends every audience with the Queen. And on this particular day, she had chosen not to wear her gloves But she must have been briefed about him, concludes Rabbi Sofrin, because at the end of their short meeting the 83-year-old Queen Elizabeth II remembered to avoid the customary handshake.


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