Basement Membrane and Repair of Injury to Peripheral Nerve: Defining a Potential Role for Macrophages, Matrix Metalloproteinases, and Tissue Inhibitor of Metalloproteinases-1

Injury to a peripheral nerve is followed by a remodeling process consisting of axonal degeneration and regeneration. It is not known how Schwann cell–derived basement membrane is preserved after injury or what role matrix metalloproteinases (MMPs) and their inhibitors play in axonal degeneration and regeneration. We showed that the MMPs gelatinase B (MMP-9), stromelysin-1 (MMP-3), and the tissue inhibitor of MMPs (TIMP)-1 were induced in crush and distal segments of mouse sciatic nerve after injury. TIMP-1 inhibitor activity was present in excess of proteinase activity in extracts of injured nerve. TIMP-1 protected basement membrane type IV collagen from degradation by exogenous gelatinase B in cryostat sections of nerve in vitro. In vivo, during the early phase (1 d after crush) and later phase (4 d after crush) after injury, induction of TNF-α and TGF-β1 mRNAs, known modulators of TIMP-1 expression, were paralleled by an upregulation of TIMP-1 and gelatinase B mRNAs. At 4 days after injury, TIMP-1, gelatinase B, and TNF-α mRNAs were localized to infiltrating macrophages and Schwann cells in the regions of nerve infiltrated by elicited macrophages. TIMP-1 and cytokine mRNA expression was upregulated in undamaged nerve explants incubated with medium conditioned by macrophages or containing the cytokines TGF-β1, TNF-α, and IL-1α. These results show that TIMP-1 may protect basement membrane from uncontrolled degradation after injury and that cytokines produced by macrophages may participate in the regulation of TIMP-1 levels during nerve repair

Novel mechanisms of endothelial dysfunction in diabetes

Diabetes mellitus is a major risk factor for cardiovascular morbidity and mortality. This condition increases the risk of developing coronary, cerebrovascular, and peripheral arterial disease fourfold. Endothelial dysfunction is a major contributor to the pathogenesis of vascular disease in diabetes mellitus patients and has recently received increased attention. In this review article, some recent developments that could improve the knowledge of diabetes-induced endothelial dysfunction are discussed

Differential Reinforcement without Extinction: An Assessment of Sensitivity to and Effects of Reinforcer Parameter Manipulations

Individuals with an Autism Spectrum Disorder (ASD) often engage in problem behavior (e.g., aggression, property destruction, self-injurious behavior; Horner, Carr, Strain et al., 2002) that may limit access to traditional social and education settings, impact their health, and pose a risk to their safety and the safety of others. One of the most common interventions used to treat problem behavior is differential reinforcement of alternative behavior (DRA; Cooper, Heron, & Heward, 2007), which are often used in combination with other interventions such as extinction (Shirley, Iwata, Kahng, Mazaleski, & Lerman, 1997). However, implementation of extinction may pose an ethical dilemma and may not be feasible depending on the setting, topography of problem behavior, and/or size of the client. In addition, its effectiveness relies on optimal treatment integrity (Fisher, Piazza, & Cataldo, 1993; Hagopian, Fisher, Sullivan, Acquisto, & LeBlanc, 1998) across all contexts and implementers. Therefore, the purpose of this study was to evaluate the effects of two variations of DRA (i.e., functional communication training; FCT) without extinction on problem behavior and communicative responses. The two FCT procedures were designed based on results of relative parameter sensitivity assessments that allowed the identification of each participant’s optimal magnitude and delay value. The study employed a reversal design to evaluate the efficiency and effectiveness of the two variations of FCT. In the current study both FCT interventions were effective in decreasing problem behavior and increasing communication for all participants. Differences in efficiency were variable across participants