Developmental critical period in genetic redox dysregulation: animal and human studies in schizophrenia

Converging evidence favors an abnormal susceptibility to oxidative stress in schizophrenia. Decreased levels of glutathione (GSH), the major cellular antioxidant and redox regulator, was observed in cerebrospinal-fluid and prefrontal cortex of patients. Importantly, abnormal GSH synthesis of genetic origin was observed: Two case-control studies showed an association with a GAG trinucleotide repeat (TNR) polymorphism in the GSH key synthesizing enzyme glutamate-cysteine-ligase (GCL) catalytic subunit (GCLC) gene. The most common TNR genotype 7/7 was more frequent in controls, whereas the rarest TNR genotype 8/8 was three times more frequent in patients. The disease associated genotypes (35% of patients) correlated with decreased GCLC protein, GCL activity and GSH content. Similar GSH system anomalies were observed in early psychosis patients. Such redox dysregulation combined with environmental stressors at specific developmental stages could underlie structural and functional connectivity anomalies. In pharmacological and knock-out (KO) models, GSH deficit induces anomalies analogous to those reported in patients. (a) morphology: spine density and GABA-parvalbumine immunoreactivity (PV-I) were decreased in anterior cingulate cortex. KO mice showed delayed cortical PV-I at PD10. This effect is exacerbated in mice with increased DA from PD5-10. KO mice exhibit cortical impairment in myelin and perineuronal net known to modulate PV connectivity. (b) physiology: In cultured neurons, NMDA response are depressed by D2 activation. In hippocampus, NMDA-dependent synaptic plasticity is impaired and kainate induced g-oscillations are reduced in parallel to PV-I. (c) cognition: low GSH models show increased sensitivity to stress, hyperactivity, abnormal object recognition, olfactory integration and social behavior. In a clinical study, GSH precursor N-acetyl cysteine (NAC) as add on therapy, improves the negative symptoms and decreases the side effects of antipsychotics. In an auditory oddball paradigm, NAC improves the mismatched negativity, an evoked potential related to pre-attention and to NMDA receptors function. In summary, clinical and experimental evidence converge to demonstrate that a genetically induced dysregulation of GSH synthesis combined with environmental insults in early development represent a major risk factor contributing to the development of schizophrenia

Incidencia, etiología y epidemiología de la brucelosis en una área rural de la província de Lleida

Fundamentos: Este estudio investiga, de forma prospectiva, la incidencia, la etiología y el perfil epidemiológico de la brucelosis humana en las comarcas del Pallars Jussà y Sobirà (Lleida), durante el período 1995-1998. Métodos: Fueron estudiados 55 pacientes diagnosticados de brucelosis. Se registró información sobre el sexo, edad, municipio de residencia, riesgo ocupacional, contacto con animales y consumo de productos lácticos no higienizados, y se obtuvieron muestras de sangre para hemocultivo. Resultados: Se registraron 10, 14, 15 y 16 casos para los años 1995, 1996, 1997 y 1998 respectivamente, y las tasas medias acumuladas fueron de 52 en el Pallars Jussà y de 129 en el Pallars Sobirà. El número de casos fue cuatro veces superior en hombres (81,8%) que en mujeres (18,2%) (RR: 4,4; IC95% 2,2-8,7). La incidencia máxima se produjo en los meses de Marzo-Abril y la mínima en los meses de verano. El 71% de los pacientes desarrollaba una actividad profesional de riesgo y hubo un claro predominio del mecanismo de contagio directo (71%). La especie animal más frecuentemente considerada fuente de infección fue la ovina (65%), seguida de la bovina (47%) y de la caprina (25%). En el Pallars Jussà hubo predominio ovino (OR: 0,3; IC95% 0,1 - 0,9) y en el Pallars Sobirà de bovino (OR: 6,6; IC95% 1,8 - 26,2). Se aislaron 27 cepas de Brucella sp, correspondiendo todas ellas a la especie melitensis. Conclusiones: La incidencia de la zoonosis en las comarcas estudiadas ha aumentado durante el período 1995-1998. Los resultados del estudio configuran un perfil epidemiológico característico de enfermedad profesional. El agente etiológico ha sido Brucella melitensis con claro predominio de la biovariedad 1.

Rendimento e qualidade da fruta do maracujazeiro-amarelo adubado com potássio, esterco de frango e de ovino

A maioria dos solos cultivados com maracujazeiro no Estado de Sergipe é de baixa fertilidade natural, o que tem ocasionado reduzida produtividade desta fruteira. Assim, objetivou-se avaliar a combinação de fontes de adubos orgânicos, esterco de frango e de ovino, às doses de potássio no rendimento e na qualidade das frutas do maracujazeiro-amarelo. O experimento foi realizado no Câmpus Rural da Universidade Federal de Sergipe. O delineamento experimental foi em blocos ao acaso, em esquema fatorial [(2x5)+1], constituído por 2 fontes de adubos orgânicos (esterco de frango na dose de 10 L e esterco de ovino na dose de 20 L) e 5 doses de potássio (0; 27; 54; 81 e 108 g planta-1) e um tratamento adicional (2,5 L de esterco de frango e 7,5 L de esterco de ovino). As variáveis estudadas foram teor de sólidos solúveis totais (SST), acidez total titulável (ATT), espessura de casca (ESPC) (mm), número de frutas/planta-1 (NFPLM) e rendimento (REND) (t ha-1), no primeiro ano de cultivo. O maracujazeiro-amarelo apresenta atributos adequados para consumo in natura e para a indústria, quando adubado com esterco de frango ou esterco de ovino associado às doses de potássio, promovendo SST entre 10,8 e 14,02 %, ATT de 8,48 a 7,57 g 100 mL-1 de suco, ESPC entre 6,52 e 7,12 mm, REND entre 27,5 e 30,24 t ha-1 e NFPLM de 28 a 29 frutas, respectivamente.

An expression of mixed animal model equations to account for different means and variances in the base population

This paper presents a general expression to predict breeding values using animal models when the base population is selected, i.e. the means and variances of breeding values in the base generation differ among individuals. Rules for forming the mixed model equations are also presented. A numerical example illustrates the procedure.

Mitochondrial DNA damage and animal longevity: insights from comparative studies

Chemical reactions in living cells are under strict enzyme control and conform to a tightly regulated metabolic program. However, uncontrolled and potentially deleterious endogenous reactions occur, even under physiological conditions. Aging, in this chemical context, could be viewed as an entropic process, the result of chemical side reactions that chronically and cumulatively degrade the function of biological systems. Mitochondria are a main source of reactive oxygen species (ROS) and chemical sidereactions in healthy aerobic tissues and are the only known extranuclear cellular organelles in animal cells that contain their own DNA (mtDNA). ROS can modify mtDNA directly at the sugar-phosphate backbone or at the bases, producing many different oxidatively modified purines and pyrimidines, as well as single and double strand breaks and DNA mutations. In this scenario, natural selection tends to decrease the mitochondrial ROS generation, the oxidative damage to mtDNA, and the mitochondrial mutation rate in long-lived species, in agreement with the mitochondrial oxidative stress theory of aging.

The Rein-Deer Drawn from the living Animal

Stockton 1789

Assessment of the discrimination of animal fat by FT_Raman spectroscopy

In recent years, there has been an increased attention towards the composition of feeding fats. In the aftermath of the BSE crisis all animal by-products utilised in animal nutrition have been subjected to close scrutiny. Regulation requires that the material belongs to the category of animal by-products fit for human consumption. This implies the use of reliable techniques in order to insure the safety of products. The feasibility of using rapid and non-destructive methods, to control the composition of feedstuffs on animal fats has been studied. Fourier Transform Raman spectroscopy has been chosen for its advantage to give detailed structural information. Data were treated using chemometric methods as PCA and PLS-DA which have permitted to separate well the different classes of animal fats. The same methodology was applied on fats from various types of feedstock and production technology processes. PLS-DA model for the discrimination of animal fats from the other categories presents a sensitivity and a specificity of 0.958 and 0.914, respectively. These results encourage the use of FT-Raman spectroscopy to discriminate animal fats.