Summary The effect of chronic infusion of gonadotropic hormone agonist Buserelin or antagonist CDB 2085 A for 15 weeks via alzet minipumps in adult male bonnet monkeys was studied. Infusion of Buserelin resulted in a decrease in the difference between serum testosterone values at 22.00 hours and 10.00 hours, decrease in responsiveness to injected Buserelin as judged by change in serum testosterone values from pre‐injection values and decrease in sperm counts. Infusion of antagonist resulted in a decrease in the difference between serum testosterone values at 22.00 hours and 10.00 hours.
Zusammenfassung Unter Verwendung von osmotischen Minipumpen wurde der Einfluß einer Dauerinfusion des GnRH‐Agonisten Buserelin bzw. des Antagonisten CDB 2085 über einen Zeitraum von 15 Wochen bei geschlechtsreifen Hutaffen untersucht. Dabei ergab sich, daß 15 Wochen nach Behandlung mit Buserelin nahezu kein Unterschied mehr zwischen dem Testosterongehalt um 10 Uhr und um 22 Uhr zu verzeichnen war. Auch nahm die individuelle Ansprechbarkeit auf Buserelin während dieser Zeit ab, d. h. nach anfänglichem Anstieg von Testosteron nach täglicher Gabe von Buserelin war dieser Effekt nach 15 Wochen nicht mehr nachweisbar. Gleichzeitig kam es unter der Therapie zu einer Abnahme der Spermatozoendichte. Auch die Infusion des Antagonisten zeigte keinen signifikanten Unterschied zwischen dem Testosteronwert um 10 Uhr und um 22 Uhr.
Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting a large number of elderly people worldwide. The current therapies for PD are symptom-based; they do not provide a cure but improve the quality of life. Muscular dysfunction is the hallmark clinical feature of PD and oxidative stress and inflammation play a critical role in its pathogenesis. Epalrestat is used for the treatment of diabetic neuropathy and is known to improve antioxidative defense mechanisms in the CNS. Therefore, in this study, we investigated the role of Epalrestat in the reserpine induced mouse model of PD.
Method:We used Swiss Albino mice for the PD model and tested for akinesia/bradykinesia, muscular rigidity, palpebral ptosis, and tremor, as well as conducting swim and open field tests. Brain samples were used to determine oxidative stress parameters and infiltration of immune cells.
Results:Epalrestat treatment significantly improved akinesia and bradykinesia, muscular dysfunctions, tremor level, and gait functions compared to the reserpine group. It also improved the latency in the swim test. Eplarestat significantly reduced lipid peroxidation and NO concentration in different brain tissues and increased the activity of antioxidative enzymes, glutathione, catalase, and superoxide dismutase.Furthermore, Epalrestat reduced neuroinflammation by reducing the number of infiltrating immune cells.
Conclusion:Eplarestat improves muscular dysfunction in PD by reducing oxidative stress and inflammation.
K E Y W O R D Sbradykinesia, Epalrestat, glutathione, oxidative-stress, Parkinson's disease
Summary. The effect of injecting agonistic and antagonistic analogues of gonadotropin releasing hormone analogues on serum testosterone levels was checked in adult and immature male bonnet monkeys. Of the agonistic analogues Buserelin, Ovurelin and D‐Phe6 Gln8 GnRH were found to be most potent in increasing serum testosterone levels in the adult male bonnet monkeys. While 27‐month‐old monkeys responded well to des Gly10 GnRH, only marginal response was observed in the case of 15‐month‐old monkeys. Studies carried out with Ovurelin indicated that it was not effective in causing desensitization in adult monkeys. The antagonistic analogue was effective in blocking nocturnal surge of serum testosterone. Based on these studies it is suggested the adult male bonnet monkeys can be effectively used for testing the activity of GnRH analogues.
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