Citations

The cardiovascular system is regulated by hemodynamic and neurohumoral mechanisms. These regulatory systems play a key role in modulating cardiac function, vascular tone, and structure. Although neurohumoral systems are essential in vascular homeostasis, they become maladaptive in disease states such as hypertension, coronary disease, and heart failure. The clinical success of ACE inhibitors has led to efforts to block other humoral systems. Neutral endopeptidase (NEP) is an endothelial cell surface zinc metallopeptidase with similar structure and catalytic site. NEP is the major enzymatic pathway for degradation of natriuretic peptides, a secondary enzymatic pathway for degradation of kinins, and adrenomedullin. The natriuretic peptides can be viewed as endogenous inhibitors of the renin angiotensin system. Inhibition of NEP increases levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) of myocardial cell origin, and C-type natriuretic peptide (CNP) of endothelial cell origin as well as bradykinin and adrenomedullin. By simultaneously inhibiting the renin-angiotensin-aldosterone system and potentiating the natriuretic peptide and kinin systems, vasopeptidase inhibitors reduce vasoconstriction, enhance vasodilation, improve sodium/water balance, and, in turn, decrease peripheral vascular resistance and blood pressure and improve local blood flow. Within the blood vessel wall, this leads to a reduction of vasoconstrictor and proliferative mediators such as angiotensin II and increased local levels of bradykinin (and, in turn, nitric oxide) and natriuretic peptides. Preliminary clinical experiences with vasopeptidase inhibitors are encouraging. Thus, the combined inhibition of ACE and neutral endopeptidase is a new and promising approach to treat patients with hypertension, atherosclerosis, or heart failure.

ABSTRACT Staphylococcus lugdunensis is a pathogen of heightened virulence that causes infections resembling those caused by Staphylococcus aureus rather than those caused by its coagulase-negative staphylococcal counterparts. Many types of S. lugdunensis infection, including native valve endocarditis, prosthetic joint infection, and intravascular catheter-related infection, are associated with biofilm etiology. Poly- N -acetylglucosamine (PNAG), a polysaccharide synthesized by products of the icaADBC locus, is a common mechanism of intercellular adhesion in staphylococcal biofilms. Here we report the characterization of ica homologues and the in vitro biofilm formation properties of a collection of S. lugdunensis clinical isolates. Isolates formed biofilms in microtiter wells to various degrees. Biofilm formation by most isolates was enhanced with glucose but diminished by sodium chloride or ethanol. icaADBC homologues were found in all S. lugdunensis isolates tested, although the locus organization differed substantially from that of other staphylococcal ica loci. icaR was not detected in S. lugdunensis , but a novel open reading frame with putative glycosyl hydrolase function is located upstream of the ica locus. icaADBC sequence heterogeneity did not explain the variability in biofilm formation among isolates. PNAG was not detected in S. lugdunensis extracts by immunoblotting with an anti-deacetylated PNAG antibody or wheat germ agglutinin. Confocal microscopy with fluorescently labeled wheat germ agglutinin showed a paucity of PNAG in S. lugdunensis biofilms, but abundant extracellular protein was visualized with SYPRO Ruby staining. Biofilms were resistant to detachment by dispersin B and sodium metaperiodate but were susceptible to detachment by proteases. Despite the genetic presence of icaADBC homologues in S. lugdunensis isolates, PNAG is not a major component of the extracellular matrix of in vitro biofilms formed by this species. Our data suggest that the S. lugdunensis biofilm matrix contains proteinaceous factors.

The Cognitive Adaptive Test/ Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) was designed for use by primary pediatric health care providers to identify children with developmental delays. This study assesses the concurrent and predictive validity of CAT/CLAMS developmental quotient (DQ) scores and the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development in healthy children without risk factors for developmental delay. Overall CAT/CLAMS DQ scores correlated significantly with Bayley MDI scores at both 12 (r=0.393; p=0.008) and 30 months (r=0.742; p=0.0001) of age. Overall CAT/CLAMS DQ scores at 12 months of age also correlated modestly with Bayley MDI scores at 30 months of age (r=0.181; p=0.036). Despite its modest predictive validity at 12 months, its satisfactory concurrent validity plus its ease and speed of administration make the CAT/CLAMS a reasonable choice for assessment of early development by primary pediatric health care providers.