Drug and Alcohol Rehabilitation: Computational Prediction of Phylogenetically Conserved Sequence Motifs for Five Different Candidate Genes in Type II Diabetic Nephropathy.

Computational Prediction of Phylogenetically Conserved Sequence Motifs for Five Different Candidate Genes in Type II Diabetic Nephropathy.

Filed under: Drug and Alcohol Rehabilitation

Iran J Public Health. 2012; 41(7): 24-33
Sindhu T, Rajamanikandan S, Srinivasan P

Computational identification of phylogenetic motifs helps to understand the knowledge about known functional features that includes catalytic site, substrate binding epitopes, and protein-protein interfaces. Furthermore, they are strongly conserved among orthologs, indicating their evolutionary importance. The study aimed to analyze five candidate genes involved in type II diabetic nephropathy and to predict phylogenetic motifs from their corresponding orthologous protein sequences.AKR1B1, APOE, ENPP1, ELMO1 and IGFBP1 are the genes that have been identified as an important target for type II diabetic nephropathy through experimental studies. Their corresponding protein sequences, structures, orthologous sequences were retrieved from UniprotKB, PDB, and PHOG database respectively. Multiple sequence alignments were constructed using ClustalW and phylogenetic motifs were identified using MINER. The occurrence of amino acids in the obtained phylogenetic motifs was generated using WebLogo and false positive expectations were calculated against phylogenetic similarity.In total, 17 phylogenetic motifs were identified from the five proteins and the residues such as glycine, leucine, tryptophan, aspartic acid were found in appreciable frequency whereas arginine identified in all the predicted PMs. The result implies that these residues can be important to the functional and structural role of the proteins and calculated false positive expectations implies that they were generally conserved in traditional sense.The prediction of phylogenetic motifs is an accurate method for detecting functionally important conserved residues. The conserved motifs can be used as a potential drug target for type II diabetic nephropathy.
HubMed – drug


Inhibition of Leishmania major PTR1 Gene Expression by Antisense in Escherichia coli.

Filed under: Drug and Alcohol Rehabilitation

Iran J Public Health. 2012; 41(6): 65-71
Kheirandish F, Bandehpour M, Haghighi A, Mahboudi F, Mohebali M, Kazemi B

Protozoa related to Trypanosome family including Leishmania, synthesize enzymes to escape from drug therapy. One of them is PTR1 that its enzymatic activity is similar to dihydrofolate reductase (DHFR). Dihydrofolate reductase – thymidylate synthase has a major role in DNA synthesis, if it is inhibited, the result would be the death of parasite. Since PTR1 activity is similar to DHFR, causes the decrease of inhibition effect of drug. The aim of this study was inhibition of Iranian L. major PTR1 expression with mRNA antisense in prokaryotic system as an approach to appear of the drugs therapeutic effects more.PTR1 gene was ligated to pACYCDuet-1 and pcDNA3 plasmids as sense and antisense plasmids, respectively. Simultaneously transfer of sense and antisense plasmids was done in E. coli strain M15. SDS-PAGE and western blot analysis were carried out to analyze the expression.Sense and antisense plasmids were prepared and confirmed by restriction analysis and PCR then simultaneously transfer of them was done. SDS-PAGE and western blot analysis showed PTR1 gene was inhibited by mRNA antisense in bacterial cells.Expression of PTR1 gene in sense plasmid was inhibited successfully by antisense plasmid.
HubMed – drug


Epidemiological features of visceral leishmaniasis in fars province, southern iran.

Filed under: Drug and Alcohol Rehabilitation

Iran J Public Health. 2012; 41(4): 94-9
Sarkari B, Hatam G, Ghatee M

To describe the epidemiological features of pediatric visceral leishmaniasis in southern Iran.This retrospective study was carried out using local hospital records of VL patients from 2001 through 2009. Data such as age, gender, place of residence, clinical signs and symptoms, treatment, history of recurrence were recorded. The collected data were statistically analyzed using SPSS software.A total of 260 cases of VL have been recorded during 2001 to 2009 in south of Iran, based on hospital records. Mean age of patients was 3.5 years with the highest prevalence in 2 years old patients. The diseases have been more common in males (60%). The main clinical signs and symptoms of the patients were fever (96.2%), hepatosplenomegaly (68.8%) and abdominal protrusion (71.9%). Most of cases were from Kazeroun County (17.5%) in Fars Province followed by Borazjan in Boushehr Province. Bone marrow aspirations have been performed in 178 of cases and Leishmania amastigotes were detected in only 50 (28.1%) cases. Glucantime has been the first drug treatment while 19.3% of cases have been treated with amphotericin B. Mortality rate was 6.2% and children under 1 year old have been the main victim of the disease. Relapse has been noted in 7.3% of patients.VL is still endemic in South of Iran, especially in Fars Province with a noticeable mortality rate. Moreover, cases of the diseases are reporting from neighboring provinces and this might be due to the spreading of the diseases to the adjacent provinces.
HubMed – drug


Assessment of ?-H2AX levels in circulating tumor cells from patients receiving chemotherapy.

Filed under: Drug and Alcohol Rehabilitation

Front Oncol. 2012; 2: 128
Garcia-Villa A, Balasubramanian P, Miller BL, Lustberg MB, Ramaswamy B, Chalmers JJ

Circulating tumor cells (CTCs) are prognostic markers in a variety of solid tumor malignancies. The potential of CTCs to be used as a “liquid biopsy” to monitor a patient’s condition and predict drug response and resistance is currently under investigation. Using a negative depletion, enrichment methodology, CTCs isolated from the peripheral blood of breast cancer patients with stage IV breast cancer undergoing DNA damaging therapy with platinum-based therapy were enriched. The enriched cell suspensions were stained with an optimized labeling protocol targeting: nuclei, cytokeratins 8, 18, and 19, the surface marker CD45, and the presence of the protein ?-H2AX. As a direct or indirect result of platinum therapy, double-strand break of DNA initiates phosphorylation of the histone H2AX, at serine 139; this phosphorylated form is referred to as ?-H2AX. In addition to ?-H2AX staining in specific locations with the cell nuclei, consistent with previous reports and referred to as foci, more general staining in the cell cytoplasm was also observed in some cells suggesting the potential of cell apoptosis. Our study underscores the utility and the complexity of investigating CTCs as predictive markers of response to various therapies. Additional studies are ongoing to evaluate the diverse ?-H2AX staining patterns we report here which needs to be further correlated with patient outcomes.
HubMed – drug



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