Hepatoblastomas in Oman : Unveiling success

Objectives: Primary malignant liver tumours account for more than 1% of all paediatric malignancies, with the most common form being hepatoblastomas (HB). Such malignancies among Arab populations have rarely been addressed in the literature. Using data from Oman’s sole national referral centre for childhood solid malignancies, this study aimed to present the nationwide Omani experience with HB over the past 21 years. Methods:This retrospective study reviewed the medical records of all children with HB who were managed in the Royal Hospital, Muscat, Oman, between January 1991 and April 2012. Clinical, radiological and laboratory characteristics were examined as well as treatments and outcomes. Results: During the study period, 15 patients with HB were treated. Of these, 10 have survived to date. Nine of the survivors were no longer receiving treatment and one patient still had the disease but was in a stable condition. Of the remaining five patients, three did not survive and two were lost to follow-up. The survival rate among patients who completed therapy was 91%. Conclusion: HB has an excellent prognosis in Oman. The main obstacle to improving outcomes among Omani patients is non-compliance with therapy

Connectivity mapping (ssCMap) to predict A20-inducing drugs and their antiinflammatory action in cystic fibrosis

Cystic fibrosis (CF) lung disease is characterized by chronic and exaggerated inflammation in the airways. Despite recent developments to therapeutically overcome the underlying functional defect in the cystic fibrosis transmembrane conductance regulator, there is still an unmet need to also normalize the inflammatory response. The prolonged and heightened inflammatory response in CF is, in part, mediated by a lack of intrinsic down-regulation of the proinflammatory NF-κB pathway. We have previously identified reduced expression of the NF-κB down-regulator A20 in CF as a key target to normalize the inflammatory response. Here, we have used publicly available gene array expression data together with a statistically significant connections’ map (sscMap) to successfully predict drugs already licensed for the use in humans to induce A20 mRNA and protein expression and thereby reduce inflammation. The effect of the predicted drugs on A20 and NF-κB(p65) expression (mRNA) as well as proinflammatory cytokine release (IL-8) in the presence and absence of bacterial LPS was shown in bronchial epithelial cells lines (16HBE14o−, CFBE41o−) and in primary nasal epithelial cells from patients with CF (Phe508del homozygous) and non-CF controls. Additionally, the specificity of the drug action on A20 was confirmed using cell lines with tnfαip3 (A20) knockdown (siRNA). We also show that the A20-inducing effect of ikarugamycin and quercetin is lower in CF-derived airway epithelial cells than in non-CF cells

Histamine Produced by Gram-Negative Bacteria Impairs Neutrophil's Antimicrobial Response by Engaging the Histamine 2 Receptor

We found that histamine (10-9 M) did not have any effect on the in vitro capture of Escherichia coli by neutrophils but accelerated its intracellular killing. In contrast, histamine (10-6 M) delayed the capture of Escherichia coli by neutrophils and reduced the amounts of pHrodo zymosan particles inside acidic mature phagosomes. Histamine acted through the H4R and the H2R, which are coupled to the Src family tyrosine kinases or the cAMP/protein kinase A pathway, respectively. The protein kinase A inhibitor H-89 abrogated the delay in bacterial capture induced by histamine (10-6 M) and the Src family tyrosine kinase inhibitor PP2 blocked histamine (10-9 M) induced acceleration of bacterial intracellular killing and tyrosine phosphorylation of proteins. To investigate the role of histamine in pathogenicity, we designed an Acinetobacter baumannii strain deficient in histamine production (hdc::TOPO). Galleria mellonella larvae inoculated with the wild-type Acinetobacter baumannii ATCC 17978 strain (1.1 × 105 CFU) died rapidly (100% death within 40 h) but not when inoculated with the Acinetobacter baumannii hdc::TOPO mutant (10% mortality). The concentration of histamine rose in the larval haemolymph upon inoculation of the wild type but not the Acinetobacter baumannii hdc::TOPO mutant, such concentration of histamine blocks the ability of hemocytes from Galleria mellonella to capture Candida albicans in vitro. Thus, bacteria-producing histamine, by maintaining high levels of histamine, may impair neutrophil phagocytosis by hijacking the H2R

Additional file 1 of Genetic diversity of macrolides resistant Staphylococcus aureus clinical isolates and the potential synergistic effect of vitamins, C and K3

Additional file 1