Therapeutic augmentation of NO-sGC-cGMP signalling: lessons learned from pulmonary arterial hypertension and heart failure

Heart Failure Reviews - The nitric oxide (NO)–guanylate cyclase (GC)–cyclic guanosine monophosphate (cGMP) pathway plays an important role in cardiovascular, pulmonary and renal...     

Natural Variant of Collagen-Like Protein A in Serotype M3 Group A Streptococcus Increases Adherence and Decreases Invasive Potential

Group A Streptococcus (GAS) predominantly exists as a colonizer of the human oropharynx that occasionally breaches epithelial barriers to cause invasive diseases. Despite the frequency of GAS carriage, few investigations into the contributory molecular mechanisms exist. To this end, we identified a naturally occurring polymorphism in the gene encoding the streptococcal collagen-like protein A (SclA) in GAS carrier strains. All previously sequenced invasive serotype M3 GAS possess a premature stop codon in the sclA gene truncating the protein. The carrier polymorphism is predicted to restore SclA function and was infrequently identified by targeted DNA sequencing in invasive strains of the same serotype. We demonstrate that a strain with the carrier sclA allele expressed a full-length SclA protein, while the strain with the invasive sclA allele expressed a truncated variant. An isoallelic mutant invasive strain with the carrier sclA allele exhibited decreased virulence in a mouse model of invasive disease and decreased multiplication in human blood. Further, the isoallelic invasive strain with the carrier sclA allele persisted in the mouse nasopharynx and had increased adherence to cultured epithelial cells. Repair of the premature stop codon in the invasive sclA allele restored the ability to bind the extracellular matrix proteins laminin and cellular fibronectin. These data demonstrate that a mutation in GAS carrier strains increases adherence and decreases virulence and suggest selection against increased adherence in GAS invasive isolates.     

Patients with prosthetic joints: Are they at risk when receiving invasive dental procedures?

Most prosthetic joint infections (PJI) are due to wound contamination at the time of surgery. Some infections occur due to the hematogenous spread of bacteria from distant sites of infection. A review of the literature fails to associate PJI with transient bacteremias from invasive dental procedures. Several authors have described conditions which, they believe, render patients with prosthetic joints more at risk for infection. Prosthetic joint patients with these "high risk" conditions have the same types of infecting organisms as other patients with PJI. This indicates that the infecting bacteria are from wound contamination or distant sites of infection and not related to dental procedure bacteremias. Based on this review, antibiotic prophylaxis is not indicated for patients with prosthetic joints when receiving invasive dental procedures, since there is no proven benefit and there are known risks involved with the use of antibiotics. However, the American Dental Association (ADA) and the American Academy of Orthopaedic Surgeons (AAOS), in an advisory statement, suggest prophylaxis for "high risk" patients. The ADA and AAOS recommend a single dose of amoxicillin, cephradine, or clindamycin when prophylaxis is selected. The dentist is ultimately responsible for making treatment recommendations for his or her patients.     

Pharmaceutical Marketing: Implications for Medical Residency Training

An educational intervention was developed to improve family practice residents' ability to obtain useful information from pharmaceutical representatives. The curriculum is based on the traditional one-on-one drug detail. The objectives are to develop residents' skills in controlling the interview, promote skills for critically analyzing drug-promotional material, and discuss ethical issues. The contents include an assessment tool, suggested readings, and interview questions with rationale. After 5 years, residents' confidence in all areas of the curriculum improved significantly.