7

Evidence of altered antioxidant systems and signs of elevated oxidative stress are reported in peripheral tissue and brain of schizophrenic patients, including low levels of glutathione (GSH), a major thiol antioxidant and redox buffer. Functional and genetic data indicate that an impaired regulation of GSH synthesis is a vulnerability factor for the disease. Impaired GSH synthesis from a genetic origin combined with environmental risk factors generating oxidative stress (e.g., malnutrition, exposure to toxins, maternai infection and diabetes, obstetrical complications, and psychological stress) could lead to redox dysregulation. This could subsequently perturb normal brain development and maturation with delayed functional consequences emerging in early adulthood. Depending on the nature and the time of occurrence of the environmental insults, the structural and functional delayed consequences could vary, giving rise to various endophenotypes. The use of animal models of GSH deficit represents a valuable approach to investigate how interactions between genetic and environmental factors lead to the emergence of pathologies found in the disease. Moreover, these models of GSH can be useful to investigate links between schizophrenia and comorbid somatic disorders, as dysregulation of the GSH system and elevated oxidative stress are also found in cardiovascular diseases and diabetes. This chapter reviews pharmacological and genetic rodent models of GSH synthesis dysregulation used to address some of the aforementioned issues. Up to date, these models revealed that GSH deficits lead to morphological, physiological, and behavioral alterations that are quite analogous to pathologies observed in patients. This includes hypofunction of NMDA receptors, alteration of dopamine neurotransmission, anomalies in parvalbumin-immunoreactive fast-spiking interneurons, and reduced myelination. In addition, a GSH deficit affects the brain in a region-specific manner, the anterior cingulate cortex and the ventral hippocampus being the most vulnerable regions investigated. Interestingly, a GSH deficit during a limited period of postnatal development is sufficient to have long-lasting consequences on the integrity of PV-IR interneurons in the anterior cingulate cortex and impairs cognitive functions in adulthood. Finally, these animal models of GSH deficit display behavioral impairments that could be related to schizophrenia. Altogether, current data strongly support a contributing role of a redox dysregulation on the development of pathologies associated with the illness and demonstrate the usefulness of these models to better understand the biological mechanisms leading to schizophrenia.

Småbruket och jordbrukspolitiken (tal vid Småbrukarnas Centralförbunds ("Pienviljelijäin Keskusliitto") möte i Åbo den 2.7.1950)

Puhe

17.7.1924

Kirje

Toimituspäällikkö Kari Vanhapiha 18/7 1975

Kirje 18.7.1975

Hki 8/7 1943

Kirje 8.7.1943

Informe sobre el viaje de pesca exploratoria entre banco de Máncora y Supe, del buque de investigación pesquera Kaiyo Maru. (7 - 30 de diciembre de 1968)

Presenta información acerca del viaje inaugural del barco de investigación japonés Kaiyo Maru, el cual tuvo a su paso el área peruana para realizar una investigación conjunta con IMARPE sobre la plataforma continental del norte del Perú; con la finalidad de comprobar la situación de las poblaciones de peces de fondo, bajo explotación e inexplotados, usando para el efecto la red de arrastre de fondo.

[s/s Ilmatar] 17/7 -29

Kirje 17.7.1929

Tasavallan Presidentti Urho Kekkosen virallinen vierailu Yhdysvaltoihin 23.-27.7.1970 (Tasavallan Presidentin saapumispuhe Washingtonissa 23.7.1970 = speech by the President of Finland, Urho Kekkonen upon his arrival in Washington, D.C. on July 23, 1970)

Puhe

Operación Eureka XXXIII, 6-7 de agosto 1975

Expone los resultados del estudio realizado durante los días 7 y 8 de agosto de 1975, con la participación de 26 embarcaciones, quienes realizaron una exploración simultánea en toda el área de distribución de la anchoveta entre los 06° y 18° S.

Operación Eureka XXX, 7-8 agosto, 1974

Muestra un cuadro general continuo de las características del stock del recurso anchoveta, su evolución en el tiempo y espacio que posibilita dar las pautas para su adecuada administración.

Junassa Chicagosta lähdettyä Kansas Cityn länsipuolella 17/7 1932

Kirje 17.7.1932

[New York] 14/7 -32

Kirje 14.7.1932

Kangasniemi 7.3.1940

Kirje