Deficit of Neurotrophins in Experimental Diabetes – Correction with a Proline-Containing Dipeptide

Neuroscience and Behavioral Physiology - Experiments on Wistar rats using a model of type 2 diabetes induced by streptozotocin (STZ) at a dose of 40 mg/kg addressed the effects of the...     

Systemic antimicrobials in the treatment of chronic periodontal diseases: a dilemma

The use of systemic antimicrobials in the treatment of acute and chronic periodontal diseases must be viewed as a dilemma. On the one hand, the approach is attractive because of the microbial nature of periodontal diseases but, on the other hand, evidence of benefit of these agents is equivocal for the majority of periodontal diseases and antimicrobials have the potential to cause harm. The disadvantages of systemic antimicrobials can be grouped under the headings of allergic reactions, superinfection, toxicity, drug interactions, patient compliance and, perhaps of most widespread importance, bacterial resistance. Mechanical debridement methods, including drainage of pus for acute periodontal abscesses, should be considered the first line treatment for most periodontal diseases. Systemic antimicrobials should be considered as adjuncts to mechanical debridement methods and, in chronic disease, never used alone as they can predispose to abscess formation. Adjunctive systemic antimicrobials may be considered in acute disease where debridement or drainage of pus is difficult, where there is local spread or systemic upset. In chronic periodontal diseases, adjunctive antimicrobials should be considered in early onset or rapidly progressive disease or in advanced chronic adult disease where mechanical therapies have failed or surgery is not a preferred option. Inadequate oral hygiene and tobacco smoking are contra-indications to the use of antimicrobials. The value of systemic antimicrobials, where other systemic risk factors co-exist, has still to be established. The role of microbial diagnosis and sensitivity testing for antimicrobial selection at this time must be questioned.     

Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis

We describe the molecular structure of the collagen fibril and how it affects collagen proteolysis or "collagenolysis." The fibril-forming collagens are major components of all mammalian connective tissues, providing the structural and organizational framework for skin, blood vessels, bone, tendon, and other tissues. The triple helix of the collagen molecule is resistant to most proteinases, and the matrix metalloproteinases that do proteolyze collagen are affected by the architecture of collagen fibrils, which are notably more resistant to collagenolysis than lone collagen monomers. Until now, there has been no molecular explanation for this. Full or limited proteolysis of the collagen fibril is known to be a key process in normal growth, development, repair, and cell differentiation, and in cancerous tumor progression and heart disease. Peptide fragments generated by collagenolysis, and the conformation of exposed sites on the fibril as a result of limited proteolysis, regulate these processes and that of cellular attachment, but it is not known how or why. Using computational and molecular visualization methods, we found that the arrangement of collagen monomers in the fibril (its architecture) protects areas vulnerable to collagenolysis and strictly governs the process. This in turn affects the accessibility of a cell interaction site located near the cleavage region. Our observations suggest that the C-terminal telopeptide must be proteolyzed before collagenase can gain access to the cleavage site. Collagenase then binds to the substrate's "interaction domain," which facilitates the triple-helix unwinding/dissociation function of the enzyme before collagenolysis.