α:Non-α and Gγ:Aγ globin chain ratios in thalassemia intermedia patients treated with hydroxyurea

Objectives: To elucidate the possible ways by which hydroxyurea molecules affect globin chain (α or β-like) synthesis. Methods: A total of 23 thalassemia intermedia patients (13 male and 10 female) aged between 5 and 26 years were treated for five months with 15 mg/(kg-day) of hydroxyurea. Hemoglobins electrophoresis and globin chain electrophoresis was performed on each sample at different time points before and during the treatment. Results: Fetal hemoglobin increased significantly in most patients and average episodes of transfusion decreased. Both Gγ and Aγ-globin chains increased significantly and α-globin:Nonα-globin chain as well as Gγ-globin:Aγ globin chains ratios decreased. Conclusions: Improvement in α:non-α ratio and consequent decrease of free α-globin chain might be the cause of beneficial effects of hydroxyurea therapy. Two patients who felt better didn't show significant increase in their fetal hemoglobin level, and this is in contradiction with the hypothesis claiming that the HbF level increase is the cause of such therapeutic effect. In spite of the unclear mechanism of action of this drug, hydroxyurea therapy had noticeable impacts on thalassemia intermedia and also sickle cell disease and even patients suffering from thalassemia major. © 2014 by the Asian Pacific Journal of Tropical Biomedicine

Detection of extended-spectrum β-lactamase (ESBL) and plasmid-borne blaCTX-M and blaTEM genes among clinical strains of Escherichia coli isolated from patients in the north of Iran

Escherichia coli is an important cause of hospital-acquired infections worldwide. Antimicrobial resistance leads to treatment failure of hospital infections caused by E. coli. Production of extended-spectrum β-lactamases (ESBLs) is one of the major causes of antibiotic resistance in these bacteria. This study aimed to investigate the frequency of blaTEM and blaCTX-M genes in ESBL-producing E. coli strains isolated from clinical specimens of patients admitted to six hospitals in the north of Iran. A total of 160 E. coli strains were isolated from various clinical samples of hospitalised patients. Antibiotic resistance patterns were determined by the Kirby�Bauer disk diffusion method. The double-disk phenotypic confirmatory test was carried out amongst β-lactam-resistant isolates to detect ESBL-producing strains. Plasmid DNA of ESBL-producing strains was extracted and subjected to PCR for detection of the blaTEM and blaCTX-M genes, and isolates were extensively verified by sequencing. The highest resistance rate was to amoxicillin; all E. coli isolates (100) were susceptible to imipenem. Amongst the 160 clinical E. coli isolates, 83 (51.9) were ESBL-positive, of which 27 (32.5) and 72 (86.7) were positive for blaTEM and blaCTX-M, respectively. This study is the first report of an ESBL phenotype disseminated in hospitals in the north of Iran. These findings showed that there was a direct relationship between the development of resistance to β-lactam antibiotics and production of TEM and CTX-M enzymes. © 2016 International Society for Chemotherapy of Infection and Cance

Oncolytic effects of Hitchner B1 strain of newcastle disease virus against cervical cancer cell proliferation is mediated by the increased expression of cytochrome C, autophagy and apoptotic pathways

Newcastle disease virus (NDV) is a potential oncolytic virus for the cancer treatment due to its ability to replicate in tumor cells. The aim of this study was to evaluate the in vitro anticancer properties of Hitchner B1 (HB1) strain of NDV on TC-1 cell line and underlying molecular mechanisms. The cytolytic effects of oncolytic HB1 strain of NDV was determined by lactate dehydrogenase (LDH) release assay. Apoptosis, intracellular reactive oxygen species (ROS) levels, cleaved caspase-3 and autophagy were evaluated by flow cytometry. Cytochrome-C and survivin protein levels were distinguished by Enzyme-Linked Immunosorbent Assay (ELISA). Our results from LDH method showed that the viability of the TC-1 cell line following HB1 NDV infection was dose-dependent and decreased significantly with increasing the dose of HB1 NDV infection (MOIs: 5, 10, and 15). Other evaluations also revealed that HB1 strain of NDV potentially led to the ROS production, and apoptosis and autophagy induction in TC-1 cell line in a dose-dependent manner. The in vitro experiments also presented that NDV treatment significantly up-regulated the expression of cytochrome-C and down-regulated the expression of survivin, as detected by ELISA assay. Our results confirmed that the HB1 NDV could be introduced as a powerful candidate for the therapy of cervical cancer. However, further examinations are needed to explain the underlying mechanisms of the HB1 NDV against TC-1 cell line and cervical cancer