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Alpha-synuclein preformed fibrils:a tool to understand Parkinson’s disease and develop disease modifying therapy

Neural Regeneration Research 2021年第11期16卷 2219-2221页

作者： Piotr Chmielarz Andrii Domanskyi Institute of Biotechnology HiLIFEUniversity of HelsinkiFinland Maj Institute of Pharmacology Polish Academy of SciencesDepartment of Brain BiochemistryKrakówPoland orion corporation orion Pharma TurkuFinland

Parkinson’s disease(PD)is the second most common neurodegenerative disorder characterized by multiple motor and nonmotor symptoms,which include,among others,constipation,sleep disturbance,bradykinesia,gait and balance abnormalities,muscle stiffness and resting *** motor symptoms are caused by progressive age-related death of dopaminergic neurons and in the vast majority of patients suffering from age-related idiopathic PD the cause of dopaminergic neurodegeneration is *** in the familial early-onset PD where genetic mutations have been identified,the molecular mechanisms driving degeneration of dopaminergic neurons are far from ***,there is no clinically approved disease-modifying therapy capable of stopping or at least slowing down the disease progression.

关键词： degeneration Alpha driving

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Toremifene in the treatment of breast cancer

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World Journal of Clinical Oncology 2014年第3期5卷 393-405页

作者： Mika VJ Mustonen Seppo Pyrh?nen Pirkko-Liisa Kellokumpu-Lehtinen orion corporation Orion PharmaFIN-02101EspooFinland Department of Oncology and Radiotherapy Turku University Hospital and University of TurkuFIN-20520TurkuFinland Department of Oncology University of TampereSchool of MedicineTampere University HospitalFIN-33520TampereFinland

Although more widespread screening and routine adjuvant therapy has improved the outcome for breast cancer patients in recent years, there remains considerable scope for improving the efficacy, safety and tolerability of adjuvant therapy in the early stage disease and the treatment of advanced disease. Toremifene is a selective estrogen receptor modifier(SERM) that has been widely used for decades in hormone receptor positive breast cancer both in early and late stage disease. Its efficacy has been well established in nine prospective randomized phase Ⅲ trials compared to tamoxifen involving more than 5500 patients, as well as in several large uncontrolled and non-randomized studies. Although most studies show therapeutic equivalence between the two SERMs, some show an advantage for toremifene. Several meta-analyses have also confirmed that the efficacy of toremifene is at least as good as that of tamoxifen. In terms of safety and tolerability toremifene is broadly similar to tamoxifen although there is some evidence that toremifene is less likely to cause uterine neoplasms, serious vascular events andit has a more positive effect on serum lipids than does tamoxifen. Toremifene is therefore effective and safe in the treatment of breast cancer. It provides not only a useful therapeutic alternative to tamoxifen, but may bring specific benefits.

关键词： Breast cancer Toremifene tamoxifen Adjuvant treatment Advanced breast cancer

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ORAZIPONE DECREASES INDUCIBLE NITRIC OXIDE SYNTHASE EXPRESSION AND NITRIC OXIDE PRODUCTION IN ACTIVATED MACROPHAGES

ORAZIPONE DECREASES INDUCIBLE NITRIC OXIDE SYNTHASE EXPRESSI...

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第十五届国际药理学大会

作者： Sareila Outi Hamalainen Mart Kankaanranta Hannu Nissinen Erkki Moilanen Eeva The Immunopharmacology Research Group Medical SchoolUniversity of Tampere and Tampere University HospitalFinland The Immunopharmacology Research Group Medical SchoolUniversity of Tampere and Tampere University HospitalFinland The Immunopharmacology Research Group Medical SchoolUniversity of Tampere and Tampere University HospitalFinland orion corporation Orion PharmaEspooFinland The Immunopharmacology Research Group Medical SchoolUniversity of Tampere and Tampere University HospitalFinland

＜正＞ In inflammation, inducible nitric oxide synthase （iNOS） produces nitric oxide （NO）, which has proinflammatory and destructive effects. Compounds that inhibit expression or activity of iNOS have a promiseas anti - inflammatory drugs in diseases like arthritis and asthma. Orazipone is a novel sulfhydryl modulating compound with anti - inflammatory properties. We investigated the effects of Oraziponeon iNOS expression and NO production in J774 murine macrophages exposed to lipopolysaccharide （LPS）.Orazipone. but not its non thiol modulating analogue inhibited iNOS protein expression and NO production in a dose - dependent manner. In addition. iNOS mRNA levels were significantly decreased by Orazipone when measured by quantitative PCR 3 h after the exposure to LPS. Orazipone prevented the activation of nuclear factor kappa B（NF kappaB）,which is a critical transcription factor for *** conclusion. Orazipone decreased iNOS expression and NO production along with its inhibitory effect on NFkappaB in activated macrophages. The effect is implicated in the anti - inflammatory action of Orazipone.

关键词： inflammation inducible nitric oxide synthase Orazipone

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