Relationship between susceptivity to triclosan sensitization by outer membrane permeabilization and cell surface hydrophobicity properties in opportunistically pathogenic Serratia species

BACKGROUND: The nosocomial opportunists Pseudomonas aeruginosa and Serratia marcescens are atypically resistant to the hydrophobic biocide triclosan due largely to outer membrane impermeability properties for hydrophobic substances. However, we have recently shown that the degree of cell envelope impermeability for triclosan differs dramatically among other opportunistically pathogenic Serratia species. Moreover, susceptivity to sensitization to triclosan by outer membrane premeabilization also differs among other intrinsically resistant species. The purpose of the present study was to determine if cell surface hydrophobicity (CSH) properties underlie susceptivity to triclosan sensitization by outer membrane premeabilization in selected species as we further characterize their cell surface properties in anticipation of investigating their propensities to form in vitro biofilms.METHODS: Three Serratia species (marcescens, fonticola, and odorifera) exhibiting disparate degrees of susceptivity to triclosan sensitization by outer membrane premeabilization were examined to determine their susceptibility levels to mechanistically-disparate hydrophobic molecules and their CSH properties. Intrinsic resistance to hydrophobic antibacterial agents was assessed using a standardized disk agar diffusion bioassay. CSH was determined using conventional crystal violet binding, hydrocarbon adherence, and 1-N-phenylnapthylamine uptake assays routinely employed in this laboratory.RESULTS: S. marcescens and S. fonticola were intrinsically resistant to all mechanistically-disparate hydrophobic antibacterial agents examined to include triclosan, while S. odorifera was susceptible. The CSH properties of all these differed only slightly, despite the disparate susceptivities of the two triclosan-resistant species to triclosan sensitization.CONCLUSION: These data suggest that phenotypic differences seen in three opportunistic Serratia species with regard to intrinsic resistance to hydrophobic antibacterial agents in general, and triclosan specifically are at least due in part to disparate abilities of their outer membranes to exclude hydrophobic substances. Moreover, susceptivity to triclosan sensitization by outer membrane premeabilization in the triclosan-resistant species S. marcescens and S. fonticola appears not to be influenced by differences in cell surface hydrophobicity properties

Soy Phosphatidylinositol–Containing Lipid Nanoparticle Prolongs the Plasma Survival and Hemostatic Efficacy of B-domain–Deleted Recombinant Canine Factor VIII in Hemophilia A Dogs

Soy phosphatidylinositol (PI) containing lipid nanoparticles prolong plasma survival, improve hemostatic efficacy, and decrease immunogenicity of human B-domain deleted Factor VIII (BDD FVIII) in Hemophilia A (HA) mice. We hypothesize that PI associated BDD FVIII is more potent than the free protein, and using mathematical modeling, have projected that PI associated BDD FVIII could be used for once-weekly prophylactic dosing in patients. To facilitate translation to the clinic, comparative plasma survival and ex vivo efficacy of PI associated recombinant canine FVIII (PI-rcFVIII) were evaluated in HA dogs. 2 HA dogs were administered a 50 U/kg iv dose of free or PI-rcFVIII. rcFVIII activity measurements and ex vivo efficacy analyses like whole blood clotting time (WBCT) and thromboelastography (TEG) were conducted on recovered plasma and whole blood samples. PI association decreased clearance (~25%) and increased plasma exposure (~1.4 fold) of rcFVIII. PI-rcFVIII treated animals had prolonged improvements in WBCTs and TEG parameters compared to free rcFVIII treated animals. Since rcFVIII is a BDD form of FVIII, these studies provide proof-of-principle that observations with human BDD FVIII in mice translate to higher animal species. Additionally, PI-rcFVIII has potential applications in canine HA management and as a bypass therapy in inhibitor-positive HA patients

Faecalibacterium prausnitzii : from microbiology to diagnostics and prognostics

We thank Dr Xavier Aldeguer and MD David Busquets from the Hospital Dr Josep Trueta (Girona, Spain) and M.D Míriam Sabat Mir from the Hospital Santa Caterina (Salt, Spain) for their help and critical discussion concerning clinical aspects. This work was partially funded by the Spanish Ministry of Education and Science through the projects SAF2010-15896 and SAF2013-43284-P, which has been co-financed with FEDER funds. Dr Sylvia H Duncan acknowledges support from the Scottish Government Food, Land and People program.Peer reviewedPostprin

Contribution of raised ICP and hypotension to CPP reduction in severe brain injury: correlation to outcome

Summary The aim of this study was to determine to what degree hypotension and ICP contribute to the reduction of cerebral perfusion pressure (CPP), particularly in light of the shift in emphasis to CPP management by the use of pressors. The study population consisted of severely head injured patients extracted retrospectively from the Traumatic Coma Data Bank and compared with 139 patients from the Smith Kline component of the American Brain Injury Consortium database where outcome was available. The percentage time that ICP exceeded 20 mm Hg and CPP less than 60 mm Hg was computed for 5 days post injury. At each hour when CPP was less than 60 mm Hg the contribution of raised ICP and low arterial pressure or both was determined. In the first cohort, hypotension was the predominant factor leading to CPP reduction. With use of the CPP concept of treatment, the major contribution to CPP shifted to ICP and arterial hypotension played less of a role. Overall, CPP management has been associated with improved outcome

A Critical Analysis of Parental Alienation Syndrome and Its Admissibility in the Family Court

Over the past three decades, parental alienation syndrome (PAS) has been proposed to explain behaviors by a child who refuses to spend time with a parent and actually denigrates that parent within the context of a child custody dispute. Although some mental health professionals and child custody evaluators, attorneys, and judges have been quick to accept and admit PAS as evidence in these disputes, there has been no consistent empirical or clinical evidence that PAS exists or that the alienator\u27s behavior is the actual cause of the alienated child\u27s behavior towards the target parent. This article attempts to help those working with custody issues understand how the PAS construct fails to meet scientific standards and should not be admissible in courts