Preclinical Evaluation of Water-Soluble Coenzyme Q10 for Therapeutic Treatment of Parkinson\u27s Disease

Parkinson\u27s disease is a common neurodegenerative disorder resulting from progressive loss of dopaminergic neurons in the substantia nigra pars compacta region of the midbrain. Mitochondrial dysfunction and oxidative stress are major contributors to this disease. Currently there is no treatment to halt the progression of Parkinson\u27s disease; there are only drugs for symptomatic relief. Previously, prophylactic treatment with a water-soluble formulation of coenzyme Q 10 was shown to reduce the loss of dopaminergic neurons in the substantia nigra and ameliorate symptoms in a paraquat-induced rat model of Parkinson\u27s disease. In this work, delivery of CoQ 10 by the water-soluble formulation shows increased bioavailability in various rat tissues, including the brain. Also observed is a decrease in the loss of dopaminergic neurons in the substantia nigra by therapeutic water-soluble CoQ 10 supplementation in a rat model. Hence, this formulation of CoQ 10 may be used to slow or halt the progression of Parkinson\u27s disease

Oxidative Toxicity in Neurodegenerative Diseases: Role of Mitochondrial Dysfunction and Therapeutic Strategies

Besides fluorine, oxygen is the most electronegative element with the highest reduction potential in biological systems. Metabolic pathways in mammalian cells utilize oxygen as the ultimate oxidizing agent to harvest free energy. They are very efficient, but not without risk of generating various oxygen radicals. These cells have good antioxidative defense mechanisms to neutralize these radicals and prevent oxidative stress. However, increased oxidative stress results in oxidative modifications in lipid, protein, and nucleic acids, leading to mitochondrial dysfunction and cell death. Oxidative stress and mitochondrial dysfunction have been implicated in many neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and stroke-related brain damage. Research has indicated mitochondria play a central role in cell suicide. An increase in oxidative stress causes mitochondrial dysfunction, leading to more production of reactive oxygen species and eventually mitochondrial membrane permeabilization. Once the mitochondria are destabilized, cells are destined to commit suicide. Therefore, antioxidative agents alone are not sufficient to protect neuronal loss in many neurodegenerative diseases. Combinatorial treatment with antioxidative agents could stabilize mitochondria and may be the most suitable strategy to prevent neuronal loss. This review discusses recent work related to oxidative toxicity in the central nervous system and strategies to treat neurodegenerative diseases

Lodovico Dolce, Parafrasi nella sesta satira di Giovenale

Edizione critica del volgarizzamento della sesta satira di Giovenale, eseguito dal Lodovico Dolce nel XVI secolo. Nell'introduzione storico-critica ci si intrattiene sull'importanza e sulla valenza delle traduzioni nel primo secolo dopo l'invenzione della stampa, nonché sui criteri traduttori del Dolce; quindi si esaminano i contenuti e le peculiarità linguistiche della parafrasi

Atypical ductal hyperplasia of the breast. Its diagnostic imaging and the role of percutaneous needle biopsy with a 14-gauge needle

Purpose. To investigate the yield of core biopsy in the histologic characterization of atypical ductal hyperplasia (ADH) and to assess the radiological patterns, if any, of this condition. Material and methods. January 1993 to October 1997 we studied 553 lesions, 8 of them with a diagnosis of ADH made on microhistologic samples obtained with 14G needles. Biopsy was performed under US guidance in 81.7% of cases and under mammographic guidance in 18.3%. The breast lesions were studied with mammography, US and MRI, the latter in one case. ADH was diagnosed by strict application of Page's and lesion extent criteria. Results. Seven of 8 lesions with a core biopsy diagnosis of ADH were submitted to surgical biopsy. The diagnosis was changed in as many as 6 of 8 cases, into typical ductal hyperplasia (1 case) and carcinoma (1 papilliferous, 3 ductal infiltrating and 1 in situ lesions). ADH was confirmed in one case only. Discussion. In agreement with other authors, we found no specific radiological patterns of ADH. Moreover, the core biopsy diagnosis of ADH requires a surgical biopsy, because ADH is often associated with carcinoma. Conclusions. Surgical biopsy is needed to diagnose ADH and therefore it is useless to perform more invasive procedures than 14G core biopsy