ABSTRACT To understand the mechanisms underlying cardiac dysfunction during ischemia reperfusion (I/R) injury, we tested the hypothesis that oxidative stress and defects in endothelium play a critical role in the activation of calpain and matrix metalloproteinases (MMP), inhibition of sarcolemmal (SL) Na+-K+-ATPase, and induction of cardiac dysfunction during I/R injury. It was observed that I/R induced depression in cardiac function and SL Na+-K+-ATPase activity was greater in hearts perfused at constant flow than in hearts perfused at constant pressure. Such a difference was associated with increased calpain activity as well as decreased endothelial nitric oxide synthase protein content and in nitric oxide production. The depression in Na+-K+-ATPase activity and decrease in protein content of Na+-K+-ATPase isoforms in I/R hearts were associated with an increase in calpain activity and translocation of calpain isoforms (I and II) from the cytosol to SL membrane as well as changes in the distribution of calpastatin. I/R induced alterations were Ca2+-dependent and were prevented by treatment with calpain inhibitors, MDL28170 and Leupeptin (Leu). These results suggest that depressions in cardiac function and SL Na+-K+-ATPase activity in the I/R hearts may be due to endothelial dysfunction as well as changes in the activity and translocation of calpain. In another set of experiments, we examined the role of oxidative stress in activation of calpain during I/R and its association with changes in the activity of MMP. Our results show depression of cardiac function and Na+-K+-ATPase activity in I/R hearts were associated with increased calpain and MMP activities. These alterations due to I/R were attenuated by ischemic preconditioning as well as treatment with antioxidant, N-acetylcysteine (NAC) and mercaptopropionylglycine (MPG). Treatment of I/R hearts with MMP inhibitor doxycycline (Dox) improved I/R-induced changes in cardiac function and Na+-K+-ATPase activity without affecting the calpain activation while treatment with calpain inhibitors, Leu and MDL 28170, reduced the MMP activity significantly in addition to attenuating the I/R-induced depression in Na+-K+-ATPase activity. These results suggests that alterations in Na+-K+-ATPase activity in I/R hearts are associated with oxidative stress and intracellular Ca2+ overload induced activation of calpain and MMP.

The purpose of this study was to evaluate masticatory muscle (MM) and temporomandibular joint (TMJ) pain patients regarding the prevalence of Posttraumatic Stress Disorder (PTSD) symptoms, and evaluate the level of psychological dysfunction and its relationship to PTSD symptoms in these patients. This study included 445 adult patients (male = 42, female = 403). Psychological questionnaires included the Symptom Check List-90-Revised (SCL-90-R), the Multidimensional Pain Inventory, the Pittsburgh Sleep Quality Index and the PTSD Check List Civilian. The total sample of patients was divided into two major groups: The MM group (n=242) and TMJ group (n=203). Each group was divided into three subgroups according to the presence of a stressor and severity of PTSD symptoms. Thirty six patients (14.9%) in the MM group and 20 patients (9.9%) in the TMJ group presented symptomatology of PTSD. MM and TMJ pain patients in the positive PTSD subgroups scored higher on all scales of the SCL-90-R (p = .000) than the other two subgroups and reached levels of distress that were indicative of psychological dysfunction. MM and TMJ pain patients in the positive PTSD subgroups were more often classified as dysfunctional than as adaptive copers and presented with more sleep disturbances than patients in the no stressor and negative PTSD subgroups. A somewhat elevated prevalence rate for PTSD symptomatology was found in the MM than in the TMJ group. Significant levels of psychological dysfunction appear limited to temporomandibular disorder patients with symptoms of PTSD.

ABSTRACT To understand the mechanisms underlying cardiac dysfunction during ischemia reperfusion (I/R) injury, we tested the hypothesis that oxidative stress and defects in endothelium play a critical role in the activation of calpain and matrix metalloproteinases (MMP), inhibition of sarcolemmal (SL) Na+-K+-ATPase, and induction of cardiac dysfunction during I/R injury. It was observed that I/R induced depression in cardiac function and SL Na+-K+-ATPase activity was greater in hearts perfused at constant flow than in hearts perfused at constant pressure. Such a difference was associated with increased calpain activity as well as decreased endothelial nitric oxide synthase protein content and in nitric oxide production. The depression in Na+-K+-ATPase activity and decrease in protein content of Na+-K+-ATPase isoforms in I/R hearts were associated with an increase in calpain activity and translocation of calpain isoforms (I and II) from the cytosol to SL membrane as well as changes in the distribution of calpastatin. I/R induced alterations were Ca2+-dependent and were prevented by treatment with calpain inhibitors, MDL28170 and Leupeptin (Leu). These results suggest that depressions in cardiac function and SL Na+-K+-ATPase activity in the I/R hearts may be due to endothelial dysfunction as well as changes in the activity and translocation of calpain. In another set of experiments, we examined the role of oxidative stress in activation of calpain during I/R and its association with changes in the activity of MMP. Our results show depression of cardiac function and Na+-K+-ATPase activity in I/R hearts were associated with increased calpain and MMP activities. These alterations due to I/R were attenuated by ischemic preconditioning as well as treatment with antioxidant, N-acetylcysteine (NAC) and mercaptopropionylglycine (MPG). Treatment of I/R hearts with MMP inhibitor doxycycline (Dox) improved I/R-induced changes in cardiac function and Na+-K+-ATPase activity without affecting the calpain activation while treatment with calpain inhibitors, Leu and MDL 28170, reduced the MMP activity significantly in addition to attenuating the I/R-induced depression in Na+-K+-ATPase activity. These results suggests that alterations in Na+-K+-ATPase activity in I/R hearts are associated with oxidative stress and intracellular Ca2+ overload induced activation of calpain and MMP.

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Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 4 uppsatser.

Thesis (M.S.)--University of Michigan, 1980.

Thesis (M.S.)--University of Michigan, 1987.

Thesis (M.S.)--University of Michigan, 1974.

Thesis (M.S.)--University of Michigan, 1987.