[Abstract unavailable

Scrapie, one of the prion diseases, is a transmissible neurodegenerative disease of sheep and other animals. Clinical symptoms of prion diseases are characterized by a long latent period, followed by progressive ataxia, tremor, and death. To study the induction of neurodegeneration during scrapie infection, we have analyzed the activities of various antioxidant enzymes and mitochondrial enzymes in cerebral cortex, brain stem, and cerebellum of scrapie-infected hamsters. The activity of mitochondrial Mn-superoxide dismutase (SOD) was decreased, while the activities of cytosolic Cu/Zn-SOD and catalase were not altered in infected brains. The activities of glutathione peroxidase and glutathione reductase were increased in scrapie-infected hamsters. The decreased activity of Mn-SOD might result in increasing oxidative stress in the mitochondria of infected brain; this concept is supported by our findings of a high level of lipid peroxidation, and low levels of ATPase and cytochrome c oxidase activity in the infected cerebral mitochondria. In addition, structural abnormalities of mitochondria have been observed in the neurons of hippocampus and cerebral cortex of infected brain. These results suggest that mitochondrial dysfunction caused by oxidative stress gives rise to neurodegeneration in prion disease.

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Transmissible spongiform encephalopathies (TSEs), also termed prion diseases, are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of these diseases is thought to be associated with the conversion of a normal protein, PrPC, into an infectious, pathogenic form, PrPSc. The PrPSc form shows greater protease resistance than PrPC and accumulates in affected individuals, often in the form of extracellular plaques. The pathogenesis and the molecular basis of neuronal cell death in these diseases are not well understood. Oxidative stress has been proposed to play an important role in the pathogenesis of several neurodegenerative disorders. In the present study, evidence of oxidative stress in scrapie, the archetype disease of the TSEs, is discussed. In addition, the mechanisms whereby oxidative stress could lead to neuronal degeneration are described.

Background: Achilles tendinopathy (AT) is a common cause of overuse injury in both athletes and nonactive individuals, especially at older ages. Due to the limited number of direct comparisons among interventions, determining the best treatment option can be difficult. Purpose: To evaluate the comparative efficacy and tolerability of nonsurgical therapies for midportion AT. Study Design: Systematic review; Level of evidence, 1. Methods: PubMed, MEDLINE, EMBASE, and Google Scholar were searched from database inception through June 20, 2019. Randomized controlled trials investigating the effect of nonsurgical therapies for midportion AT using the Victorian Institute of Sports Assessment–Achilles (VISA-A) assessment were eligible for inclusion. Primary outcome was mean change in VISA-A score from baseline. Comparisons between interventions were made through use of random-effects network meta-analysis over the short term (≤3 months) and longer term (>3 to <12 months). A safety profile was defined for each intervention by rate of all-cause discontinuation (dropout) during follow-up. Relative ranking of therapies was assessed by the surface-under-the–cumulative ranking possibilities. Results: A total of 22 studies with 978 patients met the inclusion criteria. In short-term studies, high-volume injection with corticosteroid (HVI+C) along with eccentric exercise (ECC) significantly improved the change of VISA-A score compared with that of ECC alone (standardized mean difference [SMD], 1.08; 95% CI, 0.58-1.58). Compared with ECC, acupuncture showed benefits over both the short term (SMD, 1.57; 95% CI, 1.00-2.13) and longer term (SMD, 1.23; 95% CI, 0.69-1.76). In longer-term studies, the wait-and-see approach resulted in unfavorable outcomes compared with ECC (SMD, −1.51; 95% CI, −2.02 to −1.01). Improvement was higher when ECC was combined with HVI+C (SMD, 0.53; 95% CI, 0.05-1.02) and extracorporeal shockwave therapy (ESWT) (SMD, 0.99; 95% CI, 0.48-1.49). All interventions had a similar safety profile. Conclusion: From available high-level studies, HVI+C and ESWT may be possible interventions to add along with ECC to improve longer-term outcomes.