Role of Iron Chelators, Hydroxyurea, and Splenectomy on Serum Total Antioxidant Capacity in β-Thalassemia

BACKGROUND: Iron overload is the main cause of oxidative stress in beta-thalassemia (βT) by the increased production of free radicals and reactive oxygen species. Antioxidants counteract the toxic effects of oxidative stress. AIM: This study aims to evaluate the total antioxidant capacity (TAC) and the possible impact of splenectomy, iron chelators, and hydroxyurea (hydra) on serum level of TAC. MATERIALS AND METHODS: Fifty children and adolescents with βT were studied in comparison to 25 healthy age- and sex-matched subjects. Complete medical history, clinical examination, and laboratory assessment of serum TAC, ferritin, hepcidin, and hemoglobin (Hb) were carried out. RESULTS: There was no statistically significant difference between the three groups; thalassemia major (TM), thalassemia intermedia (TI), and controls as regard age and sex. β-TM patients had significantly higher serum ferritin, serum hepcidin, and serum TAC (p < 0.000, 0.002, and 0.000, respectively) than controls. β-TI patients had significantly higher serum ferritin and serum TAC (p < 0.000) than controls. Serum TAC was lower in children with splenectomy, but this difference was not statistically significant. In addition, we observed no statistically significant difference in serum TAC of patients under different (deferasirox or deferiprone) medication. Serum TAC concentration was significantly higher in patients taking hydroxyurea (hydra) (p < 0.010). CONCLUSIONS: The study showed an increased level of serum TAC in patients with β-T in comparison with controls. Serum TAC was also increased in those taking hydroxyurea, however, it was low in βT patients under regular chelation therapy, while splenectomy had no significant effect on serum TAC

Distribució i estat de conservació de Myriostoma coliforme (Geastraceae, Basidiomycota) a Catalunya (NE península Ibèrica)

S'aporten dades sobre noves poblacions de Myriostoma coliforme (Dicks.) Corda a Catalunya descobertes els últims anys, que amplien notablement l'àrea de distribució coneguda fins ara d'aquest fong, protegit a Catalunya i inclòs a la majoria de llistes vermelles dels països europeus on és present. Es revisa la distribució i els requeriments ecològics d'aquest tàxon a Catalunya, i se n'avalua l'estatus d'amenaça.We report data of new populations of Myriostoma coliforme in Catalonia discovered during the last years and expand the knowledge of the area of occupancy of this fungus protected in Catalonia and included in several red lists of European countries. We review the distribution and ecological requirements of this species and evaluate its threat category in Catalonia according to IUCN criteri

Prevalence and Anti-Microbial Susceptibility of Hospital Acquired Infections in Two Pediatric Intensive Care Units in Egypt

BACKGROUND: Hospital-acquired (nosocomial) infection is a common serious health problem worldwide, especially in pediatric intensive care units and is associated with high mortality and morbidity, prolonged hospital stays and high cost.AIM: To determine the types of organisms involved in hospital-acquired an infection in two pediatric intensive care units during the one-year study and its anti-microbial susceptibility.MATERIAL AND METHODS: This study was carried out in the pediatric intensive care units (PICU) of Ain Shams & Cairo Universities, where 86 pediatric patients were recruited. Their age ranged from 1 month to 156 months with mean 20.7 ± 25.8 months. Male to female ratio was 37:29. Four samples were collected from each child for culture and sensitivity: blood, endotracheal aspirate, urine and skin swab.RESULTS: The most common microorganism was staphylococcus while Gram-negative bacteria were the commonest group. Amikacin and imipenem are the most sensitive antibiotics. Risk estimate for different risk factors among studied patients revealed no significance.CONCLUSION: Staphylococcus was the commonest micro-organism while Gram-negative infections were the commonest group among PICU with a predominance of Acinetobacter and Klebsiella. Respiratory infections were the most common, followed by blood-borne infection. Risk factors for mortality were not significant

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Modulation in vitro of H-ras oncogene expression by trans-splicing

In man, activated N-, K- and H-ras oncogenes have been found in around 30% of the solid tumours tested. An exon known as IDX, which has been described previously and is located between exon 3 and exon 4A of the c-H-ras pre-mRNA, allows an alternative splicing process that results in the synthesis of the mRNA of a putative protein named p19. It has been suggested that this alternative pathway is less tumorigenic than that which results in the activation of p21. We have used the mammalian trans-splicing mechanism as a tool with which to modulate this particular pre-mRNA processing to produce mRNA similar to that of mature p19 RNA. The E4A exon of the activated H-ras gene was found to be a good target for external trans-splicing. We reprogrammed the rat carnitine octanoyltransferase exon 2 to specifically invade the terminal region of H-ras. Assays performed with this reprogrammed trans-exon showed that the trans-splicing product was obtained in competition with cis-splicing of the D intron of the H-ras gene, and was associated with concomitant down-modulation of D intron cis-splicing. We also found that the exon 4A of the human c-H-ras gene underwent successive trans-splicing rounds with an external exon.This work was supported by the Asociación Española contra el Cáncer, La Marató de TV3 and Fundación Ramón Areces. S Guil was a recipient of a BEFI fellowship. We also thank Martí Cullell for revising this manuscript.Peer Reviewe

Distribució i estat de conservació de Myriostoma coliforme (Geastraceae, Basidiomycota) a Catalunya (NE península Ibèrica)

S'aporten dades sobre noves poblacions de Myriostoma coliforme (Dicks.) Corda a Catalunya descobertes els últims anys, que amplien notablement l'àrea de distribució coneguda fins ara d'aquest fong, protegit a Catalunya i inclòs a la majoria de llistes vermelles dels països europeus on és present. Es revisa la distribució i els requeriments ecològics d'aquest tàxon a Catalunya, i se n'avalua l'estatus d'amenaça.We report data of new populations of Myriostoma coliforme in Catalonia discovered during the last years and expand the knowledge of the area of occupancy of this fungus protected in Catalonia and included in several red lists of European countries. We review the distribution and ecological requirements of this species and evaluate its threat category in Catalonia according to IUCN criteri