Transfusion-transmitted virus infection in hemodialysis patients in Arar, Saudi Arabia: Prevalence, predictors and genotyping.

Transfusion-transmitted virus (TTV) is a single-stranded DNA virus that was identified in patients with post-transfusion hepatitis of non-A-to-G type. Patients with chronic renal failure on maintenance hemodialysis (HD) have a higher risk of viral infections, and the prevalence of TTV infection is common. The aim of our study was to detect TTV-DNA and its genotype in HD patients. A case-control study compromising of 63 patients on maintenance HD therapy at the Nephrology Center of Central Arar Hospital and 100 healthy individuals who were tested for TTVDNA and its genotype by semi nested-polymerase chain reaction with primers derived from the conserved open reading frame 1 (ORF1) region followed by digestion with NdeI and PstI restriction enzyme. The results show that the prevalence of TTV in HD patients was high and statistically significant; 42.9% compared with 19% in the control group. History of blood transfusion was the only significant predictor, and we found that age of patients, duration of HD, hepatitis B and C infection, aspartate aminotransferase and alanine aminotransferase levels were not significant predictors of TT virus positivity in HD patients. TTV genotype 1 (G1) was found to be the most common genotype among both HD and healthy controls. The prevalence of TTV among HD patients was significantly higher than that in healthy individuals. History of blood transfusion was the only significant predictor of TTV positivity among them. Genotype 1 was the most predominant type among HD and healthy individuals. Further studies on TTV in peritoneal dialysis patients and transplant patients are needed.

Cellular and molecular responses of Saudi chronic myeloid leukaemia patients to imatinib (STI-571): ten year experience.

BACKGROUND: The cyto-genetic hallmark of chronic myeloid leukaemia (CML), the Philadelphia chromosome (Ph), is the first consistent chromosomal abnormality that has been associated to a certain cancer type. In CML, Philadelphia chromosome is present leading to resistance to cell death and rapid proliferation. The aim of this study is to evaluate the different responses, toxicity and survival of Saudi CML patients to imatinib mesylate. METHODS: All newly diagnosed CML patients who were treated with imatinib were included in this study. We investigated haematological, and molecular and cytogenetic responses by CBC, FISH and RT-PCR respectively. Cell proliferation and apoptosis were assayed using AUC and TUNEL respectively. RESULTS: Of the 12 cases, 9 (75%) were males and 3 (25%) were female. Four (33%) of the cases were diagnosed incidentally and 8 cases (67%) presented mainly with fatigue (75%), fever (58%), and splenomegaly (83%). Signs of bleeding and rashes were rare at presentation. The majority of patients had low risk (8, 67%), and 33% had intermediate risk; but none of them had high risk CML. At the last follow up, 11 (92%) were in remissions. One patient (8%) was in remission after 3 years, 4 (33%) were in remission after 6 years, one was in remission after 7 years and 5 (42%) were in remission after 10 years. Only one patient had incomplete major molecular response (MMR) to imatinib after 12 years. The majority of the patients (10, 83%) were in MMR after 6 years and 42% of them were in MMR after 10 years of therapy. Adverse effects of imatinib were not reported by the patients. Imatinib treatment resulted in the reduction of proliferation and induction of apoptosis of CML CFU-GM cells. CONCLUSION: Imatinib mesylate is capable of treating Philadelphia chromosome-positive CP-CML without any adverse effects.

Molecular pharmacological profile of a novel thiazolinone-based direct and selective 5-lipoxygenase inhibitor.

BACKGROUND AND PURPOSE: The potency of many 5-lipoxygenase (5-LOX) inhibitors depends on the cellular peroxide tone and the mechanism of 5-LOX enzyme activation. Therefore, new inhibitors that act regardless of the mode of enzyme activation need to be developed. Recently, we identified a novel class of thiazolinone-based compounds as potent 5-LOX inhibitors. Here, we present the molecular pharmacological profile of (Z)-5-(4-methoxybenzylidene)-2-(p-tolyl)-5H-thiazol-4-one, compound C06. EXPERIMENTAL APPROACH: Inhibition of 5-LOX product formation was determined in intact cells [polymorphonuclear leukocytes (PMNL), rat basophilic leukaemia-1, RAW264.7] and in cell-free assays [homogenates, 100, 000×g supernatant (S100), partially purified 5-LOX] applying different stimuli for 5-LOX activation. Inhibition of peroxisome proliferator-activated receptor (PPAR), cytosolic phospholipase A(2) (cPLA(2) ), 12-LOX, 15-LOX-1 and 15-LOX-2 as well as cyclooxygenase-2 (COX-2) were measured in vitro. KEY RESULTS: C06 induced non-cytotoxic, direct 5-LOX inhibition with IC(50) values about 0.66 µM (intact PMNL, PMNL homogenates) and approximately 0.3 µM (cell-free PMNL S100, partially purified 5-LOX). Action of C06 was independent of the stimulus used for 5-LOX activation and cellular redox tone and was selective for 5-LOX compared with other arachidonic acid binding proteins (PPAR, cPLA(2) , 12-LOX, 15-LOX-1, 15-LOX-2, COX-2). Experimental results suggest an allosteric binding distinct from the active site and the C2-like domain of 5-LOX. CONCLUSIONS AND IMPLICATIONS: C06 was identified as a potent selective direct 5-LOX inhibitor exhibiting a novel and unique mode of action, different from other established 5-LOX inhibitors. This thiazolinone may possess potential for intervention with inflammatory and allergic diseases and certain types of cancer.