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1.  Lipoteichoic Acid from Staphylococcus aureus Induces Lung Endothelial Cell Barrier Dysfunction: Role of Reactive Oxygen and Nitrogen Species 
PLoS ONE  2012;7(11):e49209.
Tunneled central venous catheters (TCVCs) are used for dialysis access in 82% of new hemodialysis patients and are rapidly colonized with Gram-positive organism (e.g. Staphylococcus aureus) biofilm, a source of recurrent infections and chronic inflammation. Lipoteichoic acid (LTA), a cell wall ribitol polymer from Gram-positive organisms, mediates inflammation through the Toll-like receptor 2 (TLR2). The effect of LTA on lung endothelial permeability is not known. We tested the hypothesis that LTA from Staphylococcus aureus induces alterations in the permeability of pulmonary microvessel endothelial monolayers (PMEM) that result from activation of TLR2 and are mediated by reactive oxygen/nitrogen species (RONS). The permeability of PMEM was assessed by the clearance rate of Evans blue-labeled albumin, the activation of the TLR2 pathway was assessed by Western blot, and the generation of RONS was measured by the fluorescence of oxidized dihydroethidium and a dichlorofluorescein derivative. Treatment with LTA or the TLR2 agonist Pam(3)CSK(4) induced significant increases in albumin permeability, IκBα phosphorylation, IRAK1 degradation, RONS generation, and endothelial nitric oxide synthase (eNOS) activation (as measured by the p-eNOSser1177:p-eNOSthr495 ratio). The effects on permeability and RONS were effectively prevented by co-administration of the superoxide scavenger Tiron, the peroxynitrite scavenger Urate, or the eNOS inhibitor L-NAME and these effects as well as eNOS activation were reduced or prevented by pretreatment with an IRAK1/4 inhibitor. The results indicate that the activation of TLR2 and the generation of ROS/RNS mediates LTA-induced barrier dysfunction in PMEM.
PMCID: PMC3499573  PMID: 23166614
2.  Human Pharmacokinetics and Safety Profile of Finafloxacin, a New Fluoroquinolone Antibiotic, in Healthy Volunteers▿† 
Finafloxacin is a new fluoroquinolone antibiotic with the unique property of increasing antibacterial activity at pH values lower than neutral. Whereas its antibacterial activity at neutral pH matches that of other quinolones in clinical use, it is expected to surpass this activity in tissues and body fluids acidified by the infection or inflammation processes. Pharmacokinetic parameters of oral single and multiple doses of up to 800 mg of finafloxacin and safety/tolerability observations were assessed in a phase I study including 95 healthy volunteers. Finafloxacin is well absorbed after oral administration, generating maximum concentrations (Cmaxs) in plasma at least comparable to those of other fluoroquinolones, with a half-life of around 10 h. About one-third of the dose is excreted unchanged in the urine. Renal elimination appears to be a saturable process leading to slight increases of the area under the concentration-time curve extrapolated to infinity and dose normalized (AUC∞,norm) at dosages of 400 mg and above. Safety and tolerability data characterize finafloxacin as a drug with a favorable safety profile. In particular, adverse reactions regarded as class-typical of fluoroquinolones, such as, e.g., electrocardiogram (ECG) changes, neurotoxic effects, or hypoglycemia, were not observed in the study population.
PMCID: PMC3165282  PMID: 21709093
3.  Retrograde intubation in a case of ankylosing spondylitis posted for correction of deformity of spine 
Saudi Journal of Anaesthesia  2010;4(1):38-41.
Ankylosing spondylitis (AS) patients are most challenging. These patient present the most serious array of intubation and difficult airway imaginable, secondary to decrease or no cervical spine mobility, fixed flexion deformity of thoracolumbar spine and possible temporomandibular joint disease. Sound clinical judgment is critical for timing and selecting the method for airway intervention. The retrograde intubation technique is an important option when fiberoptic bronchoscope is not available, and other method is not applicable for gaining airway access for surgery in prone position. We report a case of AS with fixed flexion deformity of thoracic and thoracolumbar spine, fusion of posterior elements of cervical spine posted for lumbar spinal osteotomy with anticipated difficult intubation. An awake retrograde oral intubation with light sedation and local block is performed.
PMCID: PMC2900053  PMID: 20668567
Difficult airway; ankylosing spondylitis; Retrograde intubation

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