High throughput tissue microarray analysis of FHIT expression in diffuse large cell B-cell lymphoma from Saudi Arabia.

Recent studies have suggested a potential prognostic role of alterations of the fragile histidine triad (FHIT) gene in diffuse large B-cell lymphoma. To evaluate possible mechanisms of FHIT inactivation and to further clarify its potential prognostic relevance, we analyzed a set of 114 diffuse large B-cell lymphoma with clinical follow-up information. Tissue microarrays were analyzed by immunohistochemistry for protein expression, and corresponding DNA samples were analyzed for FHIT promotor hypermethlyation. Reduced or absent FHIT expression was found in 75 of 114 diffuse large B-cell lymphoma (66%), but was unrelated to clinical tumor stage or patient prognosis. FHIT promotor hypermethylation was observed in 29 of 93 (23%) interpretable diffuse large B-cell lymphoma. Hypermethylation was not significantly correlated to protein expression loss, which could be explained by competing mechanisms for FHIT inactivation in a substantial fraction of non FHIT hypermethylated diffuse large B-cell lymphoma. Hypermethylation was significantly associated with poor prognosis of diffuse large B-cell lymphoma patients and predominantly seen in nongerminal center diffuse large B-cell lymphoma (27%), but less frequent (13%) in germinal center diffuse large B-cell lymphoma. In summary, these data suggest that promotor hypermethylation is responsible for reduced FHIT expression in a substantial subset of diffuse large B-cell lymphoma, which is primarily composed of nongerminal center subtype with poor patient prognosis.     

Mercury exposure among residents of a building block in Shiraz, Iran

Exposure to mercury can cause serious multiorgan damage affecting the central nervous system, kidneys, liver, lungs, spleen, bone marrow, and skin. At the end of the summer of 1999, the accidental leakage of 4 liters of mercury from a container into the waterway canals resulted in mass exposure to elemental mercury among the residents of a building block of a residential area of the city of Shiraz, in the south of Iran. One hundred and eleven individuals who experienced exposure to elemental mercury were investigated. Twenty-four-hour measurement of the urine mercury level-revealed a toxic level of more than 20 microg/L in 6 children and 3 adults (including a pregnant woman). Despite normal physical and laboratory (CBC, renal and liver function tests, and urinalysis) findings, dimercaprol was prescribed. One month later during the course of the follow-up the urine mercury level in 6 patients, including the pregnant woman from the same family, was found to be again at a toxic level. The pregnant mother from the same family aborted her fetus; however, due to the lack of equipment for measuring the serum mercury level, it was not possible to confirm the relation between the mercury toxicity and the abortion. This family had kept mercury in their kitchen against health workers' instructions. The attractive physical and chemical properties of mercury could explain the continuity of exposure and poisoning in these 6 cases. It is concluded that prophylactic therapy in the presence of toxic levels of mercury, despite the presence of an asymptomatic state in exposed residents, is effective in preventing the development of signs and symptoms, though instruction of high-risk cases is the best way to combat it.     

Catecholamine-induced oligodendrocyte cell death in culture is developmentally regulated and involves free radical generation and differential activation of caspase-3

Oligodendrocyte cultures were used to study the toxic effects of catecholamines. Our results showed that catecholamine-induced toxicity was dependent on the dose of dopamine or norepinephrine used and on the developmental stage of the cultures, with oligodendrocyte progenitors being more vulnerable. A role for oxidative stress and apoptosis on the mechanism of action of catecholamines on oligodendrocyte cell death was next assessed. Catecholamines caused a reduction in intracellular glutathione levels, an accumulation in reactive oxygen species and in heme oxygenase-1, the 32 kDa stress-induced protein. All these changes were prevented by N-acetyl-L-cysteine, a thiocompound with antioxidant activity and a precursor of glutathione, and were more pronounced in progenitors than mature cells, which could contribute to their higher susceptibility. Apoptotic cell death, as assessed by activation of caspase-9 and -3 and cleavage of poly(ADP-ribose) polymerase (a substrate of caspase-3), was only observed in oligodendrocyte progenitors. Pretreatment with zVAD, a general caspase inhibitor, prevented activation of caspase-9 and -3, DNA fragmentation, and decreased progenitors cell death. Furthermore, the expression levels of procaspase-3 and the ratio of the proapoptotic protein bax to antiapoptotic protein bcl-xl were several folds higher in immature than mature oligodendrocytes. Taken together, these results strongly suggest that the catecholamine-induced cytotoxicity in oligodendrocytes is developmentally regulated, mediated by oxidative stress, and have characteristics of apoptosis in progenitor cells.     

In vitro evaluation of the quality of essential drugs on the Tanzanian market

We evaluated the in vitro availability and its stability under simulated tropical conditions of various formulations of four essential drugs marketed in Tanzania. We obtained 22 formulations (containing paracetamol, acetylsalicylic acid, chloroquine or sulphadoxine/pyrimethamine) from wholesale pharmacies in Dar es Salaam and the Medical Stores Department (Tanzania). The drug content, in vitro availability (dissolution) and its stability under simulated tropical conditions were determined using methods specified in the United States Pharmacopoeia (USP) 24 monograph of the respective drugs. All formulations passed the pharmacopoeia requirements for the drug content. However, seven formulations (three acetylsalicylic acid, two sulphadoxine/pyrimethamine and two paracetamol) failed to meet the USP 24 tolerance limits for dissolution. Another five formulations (three paracetamol and two chloroquine) failed to meet the dissolution tolerance limits after being subjected to an accelerated stability test under simulated tropical conditions (75% RH/40 degrees C) for 6 months. The study has demonstrated the presence on the Tanzanian market of essential drug formulations that met potency requirements and yet had unsatisfactory in vitro availability as they were not robust enough to withstand storage under simulated tropical conditions.     

Nutritional rickets and z scores for height in the United Arab Emirates: To D or not to D?

Background: Vitamin D deficiency is still prevalent worldwide, including the Middle East. A cohort of patients with nutritional rickets was treated with vitamin D₂ (ergocalciferol) alone. After this intervention, patients were followed to document changes in z scores for height after treatment. The secondary aim was to determine the proportion of affected children who had vitamin D deficiency or calcium deficiency.
Methods: Z score for height was calculated as the difference between the observed value and the median value, divided by the SD of the population. Z scores were compared in patients before and after treatment.
Results: The improvement in z score after treatment was 0.86 ± 0.95. The 95% confidence interval for the mean difference was 1.32–0.40 ( t  = 3.95, P  < 0.001). With a diagnostic cut-off for 25 hydroxyvitamin D₃ (25D) deficiency of <25 nmol/L, only half were diagnosed with severe vitamin D deficiency. The remaining patients had presumable calcium deficiency. The alkaline phosphatase (ALP) was negatively correlated to z scores, implying that higher ALP concentrations predicted severe bone disease (lower z scores). The variables 25D and age were moderately and positively correlated (Pearson's r  = 0.59, 95%CI: 0.15–0.84; P  = 0.01), indicating that younger infants had the lowest 25D levels.
Conclusion: Vitamin D alone was efficient in resolving radiological and biochemical disturbances as well as improving z scores for height in a cohort of children with nutritional rickets, which included patients with 25D deficiency as well as calcium deficiency. The results support the hypothesis of the interplay and continuum of 25D deficiency and calcium deficiency in the pathogenesis of rickets.     

Binaural sensitivity to temporal fine structure and lateralization ability in children with suspected (central) auditory processing disorder

Objective

Previous studies have shown that a subgroup of children with suspected (central) auditory processing disorder (SusCAPD) have insufficient ability to use binaural cues to benefit from spatial processing. Thus, they experience considerable listening difficulties in challenging auditory environments, such as classrooms. Some researchers have also indicated the probable role of binaural temporal fine structure (TFS) in the perceptual segregation of target signal from noise and hence in speech perception in noise. Therefore, in the present study, in order to further investigate the underlying reason for listening problems against background noise in this group of children, their performance was measured using binaural TFS sensitivity test (TFS-LF) as well as behavioral auditory lateralization in noise test, both of which are based on binaural temporal cues processing.