INFLUENCE OF TOPICAL RETAPAMULIN (1%) OINTMENT, SOFINOX- RD CREAM, SOFINOX CREAM (2%), ZINC FUSIDATE CREAM (2%) AND ZINC FUSIDATE OINTMENT (2%) ON NASAL MUCOSAL SURFACE SAFETY IN NEW ZEALAND ALBINO RABBITS

Objective: To investigate the comparative safety of Retapamulin 1% ointment, Sodium fusidate 0.25%, Sofinox 2% cream, Zinc fusidate 2% cream and Zinc fusidate 2% ointment on nasal mucosal surface in rabbits.Methods: In the experiment a total of 30 adult New Zealand albino rabbits of either sex were used. The rabbits were divided into five groups of six rabbits each. A thin layer of the drug was applied in the right nostril and left nostril was kept as control (no treatment) to their corresponding treatment group. Nasal safety of these drugs was assessed with the help of a symptom scoring system and photographic observations.Results: There was significant decrease of nasal rubbing (Rhinocnesmus) behaviors in experimental animals of Sofinox RD cream (p<0.001), Sofinox 2% cream (p<0.001), Zinc fusidate cream (p<0.001) and Zinc fusidate ointment (p<0.001) treated groups when compared with Retapamulin 1% ointment treated group. More redness was observed in nasal mucosal surface of both nostrils (Right nostril- Retapamulin 1% ointment, Left nostril- Control) of Retapamulin group animals in comparison with Sofinox RD cream, Sofinox 2% cream, Zinc fusidate 2% cream and Zinc fusidate 2% ointment group animals.Conclusion: In the present study, the comparative safety of test drugs on nasal mucosal surface of rabbits were found as- Zinc fusidate ointment > Zinc fusidate cream > Sofinox RD cream ~ Sofinox 2% cream > Retapamulin 1% ointment. Further, clinical evaluation has to be performed to precisely define the safety of Zinc fusidate ointment, Zinc fusidate cream, Sofinox RD cream and Sofinox 2% cream on nasal mucosal surface of human subjects.Â

Adaptive Variation Regulates the Expression of the Human <i>SGK1</i> Gene in Response to Stress

The Serum and Glucocorticoid-regulated Kinase1 (SGK1) gene is a target of the glucocorticoid receptor (GR) and is central to the stress response in many human tissues. Because environmental stress varies across habitats, we hypothesized that natural selection shaped the geographic distribution of genetic variants regulating the level of SGK1 expression following GR activation. By combining population genetics and molecular biology methods, we identified a variant (rs9493857) with marked allele frequency differences between populations of African and European ancestry and with a strong correlation between allele frequency and latitude in worldwide population samples. This SNP is located in a GR-binding region upstream of SGK1 that was identified using a GR ChIP-chip. SNP rs9493857 also lies within a predicted binding site for Oct1, a transcription factor known to cooperate with the GR in the transactivation of target genes. Using ChIP assays, we show that both GR and Oct1 bind to this region and that the ancestral allele at rs9493857 binds the GR-Oct1 complex more efficiently than the derived allele. Finally, using a reporter gene assay, we demonstrate that the ancestral allele is associated with increased glucocorticoid-dependent gene expression when compared to the derived allele. Our results suggest a novel paradigm in which hormonal responsiveness is modulated by sequence variation in the regulatory regions of nuclear receptor target genes. Identifying such functional variants may shed light on the mechanisms underlying inter-individual variation in response to environmental stressors and to hormonal therapy, as well as in the susceptibility to hormone-dependent diseases.</p

Adaptive Variation Regulates the Expression of the Human SGK1 Gene in Response to Stress

The Serum and Glucocorticoid-regulated Kinase1 (SGK1) gene is a target of the glucocorticoid receptor (GR) and is central to the stress response in many human tissues. Because environmental stress varies across habitats, we hypothesized that natural selection shaped the geographic distribution of genetic variants regulating the level of SGK1 expression following GR activation. By combining population genetics and molecular biology methods, we identified a variant (rs9493857) with marked allele frequency differences between populations of African and European ancestry and with a strong correlation between allele frequency and latitude in worldwide population samples. This SNP is located in a GR-binding region upstream of SGK1 that was identified using a GR ChIP-chip. SNP rs9493857 also lies within a predicted binding site for Oct1, a transcription factor known to cooperate with the GR in the transactivation of target genes. Using ChIP assays, we show that both GR and Oct1 bind to this region and that the ancestral allele at rs9493857 binds the GR-Oct1 complex more efficiently than the derived allele. Finally, using a reporter gene assay, we demonstrate that the ancestral allele is associated with increased glucocorticoid-dependent gene expression when compared to the derived allele. Our results suggest a novel paradigm in which hormonal responsiveness is modulated by sequence variation in the regulatory regions of nuclear receptor target genes. Identifying such functional variants may shed light on the mechanisms underlying inter-individual variation in response to environmental stressors and to hormonal therapy, as well as in the susceptibility to hormone-dependent diseases

Decision support tool for differential diagnosis of Acute Respiratory Distress Syndrome (ARDS) vs Cardiogenic Pulmonary Edema (CPE): a prospective validation and meta-analysis

Introduction: We recently presented a prediction score providing decision support with the often-challenging early differential diagnosis of acute lung injury (ALI) vs cardiogenic pulmonary edema (CPE). To facilitate clinical adoption, our objective was to prospectively validate its performance in an independent cohort. Methods: Over 9 months, adult patients consecutively admitted to any intensive care unit of a tertiary-care center developing acute pulmonary edema were identified in real-time using validated electronic surveillance. For eligible patients, predictors were abstracted from medical records within 48 hours of the alert. Post-hoc expert review blinded to the prediction score established gold standard diagnosis. Results: Of 1,516 patients identified by electronic surveillance, data were abstracted for 249 patients (93% within 48 hours of disease onset), of which expert review (kappa 0.93) classified 72 as ALI, 73 as CPE and excluded 104 as “other”. With an area under the curve (AUC) of 0.81 (95% confidence interval =0.73 to 0.88) the prediction score showed similar discrimination as in prior cohorts (development AUC = 0.81, P = 0.91; retrospective validation AUC = 0.80, P = 0.92). Hosmer-Lemeshow test was significant (P = 0.01), but across eight previously defined score ranges probabilities of ALI vs CPE were the same as in the development cohort (P = 0.60). Results were the same when comparing acute respiratory distress syndrome (ARDS, Berlin definition) vs CPE. Conclusion: The clinical prediction score reliably differentiates ARDS/ALI vs CPE. Pooled results provide precise estimates of the score’s performance which can be used to screen patient populations or to assess the probability of ALI/ARDS vs CPE in specific patients. The score may thus facilitate early inclusion into research studies and expedite prompt treatment. Electronic supplementary material The online version of this article (doi:10.1186/s13054-014-0659-x) contains supplementary material, which is available to authorized users