Association between dietary and beverage consumption patterns in the SUN (Seguimiento Universidad de Navarra) cohort study.

OBJECTIVE: The objective of the present study was to determine the dietary patterns of a Mediterranean cohort and relate them to the observed patterns of beverage consumption. DESIGN: Prospective cohort study. Dietary habits were assessed with a semi-quantitative FFQ validated in Spain. A principal components factor analysis was used to identify dietary patterns and to classify subjects according to their adherence to these patterns. The association between adherence to each dietary pattern and beverage consumption was assessed cross-sectionally. In a longitudinal analysis (2-year follow-up), the relationship between adherence to the baseline dietary patterns and the likelihood of changing alcohol consumption was ascertained. SETTING: The SUN (Seguimiento Universidad de Navarra) study is conducted in Spain. SUBJECTS: In total, 15 073 university graduates were included in the analyses. RESULTS: Two major dietary patterns were identified. We labelled them as 'Western dietary pattern' (WDP) and 'Mediterranean dietary pattern' (MDP). Higher adherence to the WDP was associated with higher consumption of carbonated beverages and whole-fat milk (P for trend <0.001), while higher adherence to the MDP was associated with higher consumption of decaffeinated coffee, orange juice, other natural juices, diet carbonated drinks, low-fat milk and bottled water (P for trend <0.001). Participants with higher adherence to the WDP were less likely to decrease their alcohol consumption during follow-up (OR between extreme quintiles = 0.68; 95 % CI 0.56, 0.84). By contrast, participants with higher adherence to the MDP were less likely to increase their alcohol consumption (OR = 0.66, 95 % CI 0.46, 0.95). CONCLUSION: In this cohort of university graduates, a healthier dietary pattern was associated with a healthier pattern of beverage consumption.

Diferencias en estilos de vida y calidad de la información autorreferida según nivel de estudios: el proyecto SUN / Differences in lifestyle and quality of self-reported information according to educational level: the SUN cohort study

El objetivo de este estudio fue valorar las diferencias en estilos de vida y calidad de información autorreferida según el nivel de estudios, a partir de la base de datos de participantes de una cohorte prospectiva. Para ello realizamos un análisis transversal basal de los participantes(n=15404) de la cohorte SUN. En los universitarios el índice de masa corporal y la prevalencia de hipercolesterolemia fueron signifi cativamenteinferiores, mientras que la ingesta de alcohol fue ligeramente superior. En el resto de las 37 variables comparadas sobre estilo de vida o alimentación no existieron diferencias estadísticamente signifi cativas.En cambio, los no universitarios tenían más datos perdidos (odds ratio ajustada: 1,99; IC 95%: 1,68-2,37). Excepto tres excepciones, no se apreciaron diferencias signifi cativas en el estilo de vida o alimentaciónsegún el nivel de estudios. Sin embargo, la calidad de las respuestas fue muy superior en los universitarios

We assessed differences across educational levels in lifestyle to evaluate selection bias and quality of self-reported information in the baseline data of participants in a prospective cohort. A baseline cross-sectional analysis of the data of participants (n=15,404) in the SUN cohort was conducted. Among participants with higher (university) educationallevels, body mass index and prevalence of high blood cholesterol were signifi cantly lower than in participants with lower educational level,whereas alcohol consumption was slightly higher. In another 37 lifestyle/nutrition variables compared, there were no signifi cant differences. Onother hand, missing data were more frequently found among participants with lower education (adjusted odds ratio: 1.99; 95% CI; 1.68-2.37). With only 3 exceptions, no signifi cant differences in lifestyle or foodhabits were found between educational levels. However, the quality of self-reported information was considerably greater among more highly educated participants10pt;}

Diferencias en estilos de vida y calidad de la información autorreferida según nivel de estudios: el proyecto SUN / No disponible

El objetivo de este estudio fue valorar las diferencias en estilos de viday calidad de información autorreferida según el nivel de estudios, apartir de la base de datos de participantes de una cohorte prospectiva.Para ello realizamos un análisis transversal basal de los participantes(n=15404) de la cohorte SUN. En los universitarios el índice de masacorporal y la prevalencia de hipercolesterolemia fueron signifi cativamenteinferiores, mientras que la ingesta de alcohol fue ligeramente superior.En el resto de las 37 variables comparadas sobre estilo de vida oalimentación no existieron diferencias estadísticamente signifi cativas.En cambio, los no universitarios tenían más datos perdidos (odds ratioajustada: 1,99; IC 95%: 1,68-2,37). Excepto tres excepciones, no seapreciaron diferencias signifi cativas en el estilo de vida o alimentaciónsegún el nivel de estudios. Sin embargo, la calidad de las respuestasfue muy superior en los universitarios(AU)

We assessed differences across educational levels in lifestyle to evaluateselection bias and quality of self-reported information in the baselinedata of participants in a prospective cohort. A baseline cross-sectionalanalysis of the data of participants (n=15,404) in the SUN cohort wasconducted. Among participants with higher (university) educationallevels, body mass index and prevalence of high blood cholesterol weresignifi cantly lower than in participants with lower educational level,whereas alcohol consumption was slightly higher. In another 37 lifestyle/nutrition variables compared, there were no signifi cant differences. Onother hand, missing data were more frequently found among participantswith lower education (adjusted odds ratio: 1.99; 95% CI; 1.68-2.37).With only 3 exceptions, no signifi cant differences in lifestyle or foodhabits were found between educational levels. However, the quality ofself-reported information was considerably greater among more highlyeducated participants(AU)

Adherence to Mediterranean diet and risk of developing diabetes: prospective cohort study.

OBJECTIVE: To assess the relation between adherence to a Mediterranean diet and the incidence of diabetes among initially healthy participants. DESIGN: Prospective cohort study with estimates of relative risk adjusted for sex, age, years of university education, total energy intake, body mass index, physical activity, sedentary habits, smoking, family history of diabetes, and personal history of hypertension. SETTING: Spanish university department. PARTICIPANTS: 13 380 Spanish university graduates without diabetes at baseline followed up for a median of 4.4 years. MAIN OUTCOME MEASURES: Dietary habits assessed at baseline with a validated 136 item food frequency questionnaire and scored on a nine point index. New cases of diabetes confirmed through medical reports and an additional detailed questionnaire posted to those who self reported a new diagnosis of diabetes by a doctor during follow-up. Confirmed cases of type 2 diabetes. RESULTS: Participants who adhered closely to a Mediterranean diet had a lower risk of diabetes. The incidence rate ratios adjusted for sex and age were 0.41 (95% confidence interval 0.19 to 0.87) for those with moderate adherence (score 3-6) and 0.17 (0.04 to 0.75) for those with the highest adherence (score 7-9) compared with those with low adherence (score <3). In the fully adjusted analyses the results were similar. A two point increase in the score was associated with a 35% relative reduction in the risk of diabetes (incidence rate ratio 0.65, 0.44 to 0.95), with a significant inverse linear trend (P=0.04) in the multivariate analysis. CONCLUSION: Adherence to a Mediterranean diet is associated with a reduced risk of diabetes.

Fracturas lentas o fracturas por sobrecarga / Slow-developing fractures or stress fractures

No disponible

Cleaved caspase-3, caspase-7 and poly (ADP-ribose) polymerase are complementarily but differentially expressed in human medulloblastomas.

Expression of cleaved caspase-3, cleaved caspase-7 and specific product of caspase-dependent Poly (ADP-Ribose) Polymerase (PARP) cleavage have been examined by immunohistochemistry in seven human medulloblastomas. Cleaved caspase-3 and cleaved PARP expression parallels apoptosis as revealed with classical morphological criteria and with the method of in situ end-labelling of nuclear DNA fragmentation. Cleaved PARP co-localizes cleaved caspase-3 in the majority of tumors and areas thus indicating that caspase-3 is a major effector caspase leading to apoptosis in these tumors. Yet cleaved caspase-7 was also expressed in a small number of cells in four of seven tumors, but was the predominant caspase associated with cleaved PARP in one medulloblastoma. These findings indicate that effector caspase-3 and -7 may act in association, although caspase-7 may be exceptionally dominant in selected tumors.

Molecular genetics of radiographically defined de novo glioblastoma multiforme.

Glioblastoma multiforme (GBM) represents the final endpoint of anaplastic progression in astrocytomas. GBM which arise without clinical evidence of a prior low-grade astrocytoma (LGA) have been designated de novo GBM, and are thought to develop rapidly from initial tumour formation. However, a purely clinical definition of de novo GBM does not exclude a long-standing, asymptomatic low-grade tumour. This study therefore sought to determine the genetic features of a unique group of cases in which GBMs were documented to have arisen radiographically in defined period of time (radiographically defined de novo GBM). Clinical and genetic features were examined in a group of 11 patients with a histological diagnosis of high-grade astrocytoma at first biopsy and radiographically defined de novo GBM. The mean age of the patients at tumour diagnosis was 62 years (range 32-87). Six of 11 tumours arose in the temporal lobes. Eight of 11 tumours had epidermal growth factor receptor (EGFR) overexpression, and EGFR gene amplification was found in five of the six analysed cases. Overexpression of p53 was observed in only one tumour, and a TP53 mutation was present in this case. p16 immunostaining was undetectable in 10 cases, and homozygous deletion of CDKN2A was observed in four of the six studied tumours. pRb expression was lost in four tumours. Mutations in the PTEN gene were detected in two of six cases. The results in this unique group of cases confirms the prior hypothesis that the profile of genetic alterations in de novo GBM is distinct from that of GBM arising from a known LGA, and that these specific genetic pathways promote the rapid development of GBM.

Fracturas lentas o fracturas por sobrecarga. Contribución clínica / Slowly developing fractures or stress fractures

No disponible

NF-kB immunoreactivity is observed in association with beta A4 diffuse plaques in patients with Alzheimer's disease.

Transcription factor NF-kB is widely expressed in the nervous system and, particularly, in synaptic terminals. Increased NF-kB expression in synaptosomes has been observed as a result of activity, and beta A4 deposition. In the present study we have examined NF-kB immunoreactivity, by means of NF-kB p65 immunohistochemistry, in the brains of seven patients with Alzheimer's disease, two patients with Creutzfeldt-Jakob disease associated with PrP amyloid deposition, and seven age-matched controls. Our purpose was to examine possible NF-kB induction associated to beta A4 or PrP deposition in these diseases. Punctate NF-kB immunoreactivity was constantly found in the neuropil of diffuse beta A4 deposits but not in dystrophic neurites of senile plaques. In addition, NF-kB immunoreactivity was found in the nuclei of neurons, but not in the nuclei of reactive astrocytes, in the vicinity of diffuse plaques, thus suggesting NF-kB translocation to the nucleus. Finally, a few neurons with neurofibrillary degeneration showed increased cytoplasmic NF-kB immunoreactivity probably secondary to abnormal compartmentation or impaired transport of NF-kB. No similar modifications in NF-kB immunoreactivity were observed in association with PrP deposits in patients with Creutzfeldt-Jakob disease. Since it has been suggested that the presence of NF-kB in synapses may indicate the existence of a new pathway of gene transcription, the present results support the concept that this pathway may be activated by the deposition of beta A4 in diffuse plaques in Alzheimer's disease.

Dystrophic neurites of senile plaques are defective in proteins involved in exocytosis and neurotransmission.

Dystrophic neurites are major components of neuritic (both immature and mature) senile plaques in Alzheimer disease. Previous studies have shown strong immunoreactivity for different neuropeptides, and chromogranin A, a protein associated with dense-core vesicles, in dystrophic neurites. In the present study, antibodies to synaptophysin, synapsin, Rab3a and synaptotagmin (synaptic vesicle proteins), and SNAP-25 (synaptosomal-associated protein of 25 kD) and syntaxin (presynaptic plasma membrane proteins) have been used to learn about the dystrophic neurite equipment of proteins that are necessary for the docking and fusion of synaptic vesicles, and then for exocytosis and neurotransmission. The present results have shown that, although most neuritic senile plaques have chromogranin A- and SNAP-25-immunoreactive dystrophic neurites, only a percentage of them contain synaptophysin, and a minority contain synaptotagmin and Rab3a. Dystrophic neurites do not contain synapsin and syntaxin. These results show that dystrophic neurites of senile plaques are defective in proteins that control exocytosis and neurotransmission.

Bcl-2 and Bax protein expression in neurofibrillary tangles in progressive supranuclear palsy.

Double-labeling immunohistochemistry to Bcl-2 and Bax and to tau protein was examined in the brains of patients with progressive supranuclear palsy (PSP) to study the possible relationship between the expression of Bax and Bcl-2 proteins and neurofibrillary tangle formation. No differences between Bcl-2 and Bax immunoreactivity in neurons of the brain stem were observed in PSP patients and controls. Moreover, the intensity of Bcl-2 and Bax immunoreactivity was similar in tangle-bearing and non-tangle-bearing neurons in PSP patients. These results suggest that Bcl-2 and Bax are probably not implicated in neurofibrillary tangle formation in PSP.

Bcl-2 and Bax protein expression in Alzheimer's disease.

Beta-amyloid deposition and neurofibrillary degeneration are important pathological findings in the brains of patients with Alzheimer's disease (AD). In the present study, we have examined Bcl-2 and Bax immunoreactivity in the hippocampus of AD cases, with special attention to the possible relationship between Bcl-2 and Bax immunoreactivity, and neurofibrillary degeneration and senile plaques. Different antibodies were used, including Bcl-2 (N-19), Bcl-2 (BioGenex), Bax (P-19) and Bax (N-20), and their specificity was tested on Western blots of brain homogenates. No differences between Bcl-2 and Bax immunoreactivity in tangle-bearing and non-tangle-bearing neurons were observed, thus suggesting that Bcl-2 and Bax do not participate in tangle formation. Overexpression of Bcl-2 protein in reactive glial cells surrounding senile plaques suggests that Bcl-2 may play a role in the survival of reactive glia. On the other hand, overexpression of Bax immunoreactivity in dystrophic neurites of senile plaques suggests that Bax is associated with neurite degeneration in senile plaques. Finally, Bax (P-19), but not Bax (N-20), immunoreactivity was localized in amyloid fibrils of senile plaques. Since Western blots to Bax (P-19) recognize multiple bands in addition to the expected band of about 21 kDa, it is suggested that Bax (P-19) immunoreactivity of amyloid fibrils is not specific.

Bcl-2 and Bax proteins in Lewy bodies from patients with Parkinson's disease and Diffuse Lewy body disease.

Double-labelling immunohistochemistry of Bcl-2 and Bax, and ubiquitin (as a marker of Lewy bodies) was examined in the brains of patients with Parkinson's disease and Diffuse Lewy body disease to learn about possible modifications of protein expression and the presence of Lewy bodies. Bcl-2 and Bax immunoreactivities were observed in Lewy body-bearing and non-Lewy body-bearing neurons in patients with parkinsonism. These results show that Bcl-2 and Bax are probably not implicated in Lewy body formation and that the presence of Lewy bodies does not have a direct impact on the expression of Bcl-2 and Bax proteins in individual neurons.

Chronic effects of single intrastriatal injections of 6-hydroxydopamine or 1-methyl-4-phenylpyridinium studied by microdialysis in freely moving rats.

Extracellular dopamine (DA) and its main cerebral metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were measured by bilateral striatal microdialysis in rats at different times (2, 7, 15 and 60 days) after unilateral administration into the right striatum of 1-methyl-4-phenylpyridinium ion (MPP+) or 6-hydroxydopamine (6-OHDA). In both cases the decrease in extracellular dopamine did not exceed 40% of control values. The response of DOPAC and HVA depended on the treatment: MPP+ caused a marked acute decrease in the dopamine metabolites but allowed a progressive recovery that was very evident after 60 days; 6-OHDA caused a progressive decrease in the dopamine metabolites throughout the two months of the study. Tyrosine hydroxylase immunostaining revealed severe neuronal loss in substantia nigra two months after striatal administration of 6-OHDA, whereas no significant neuronal loss was found at the same time after MPP+ administration. A bilateral challenge infusion of MPP+ through the microdialysis probe was used to assess the dopaminergic capacity of both striata: at all the times studied there was a sharp depletion of DA on the non-lesioned side; both MPP(+)- and 6-OHDA-treated striata were unresponsive after a short time (2 days); after 2 months the response in MPP(+)-lesioned rats was similar on both sides, whereas 6-OHDA-lesioned striata were still unresponsive to MPP+. In rats, then, the effects of MPP+ could be partly reversed whereas the effects of 6-OHDA were not. These results suggest that neurotoxins causing striatal dopamine loss may act through different mechanisms, which could be significant for the etiopathogenic development of Parkinson's disease.

Increased beta-amyloid precursor protein expression in astrocytes in the gerbil hippocampus following ischaemia: association with proliferation of astrocytes.

Increases in beta-amyloid precursor proteins (APP), which include the beta-amyloid senile plaque protein present in patients with Alzheimer's disease, have been shown to occur in models of neuronal damage and neurotoxic cell injury. This observation led us to examine the expression of these proteins after transient ischaemic episodes in the gerbil. Animals were killed 2-28 days after ischaemia and APP were detected by immunocytochemistry at the light and electron microscopic levels with an antibody raised against the C-terminal region of these proteins. The gliotic reaction was also examined using glial fibrillary acid protein (GFAP) immunoreactivity. Two days after ischaemia, neuronal cell death was observed in the hippocampal CA1 region accompanied by astrocyte hypertrophy. These hypertrophic astrocytes were found to be GFAP positive but stained weakly for APP. Seven days after ischaemia both astrocyte hypertrophia and hyperplasia, with identified mitotic figures, were observed. These hyperplasic astrocytes were intensely stained by the APP antibody, and were observed up to 28 days after ischaemia. This shows that neuronal cell death produced by transient ischaemia is followed by an increased APP expression which appears to be associated with the hyperplasic astrocytes but not with the initial hypertrophy of this cell population. These results, when taken together with those obtained in other models of neuronal damage or death, clearly suggest that APP expression follows neuronal death and is associated with astrocyte proliferation.

Naturally occurring cell death in the developing cerebral cortex of the rat. Evidence of apoptosis-associated internucleosomal DNA fragmentation.

Naturally occurring dead cells in the developing rat neocortex, subcortical white matter and hippocampus, which increase in number during the first postnatal week and decrease thereafter to disappear by the end of the first month, were examined by in situ labeling of nuclear DNA fragmentation. These cells showed peripheral chromatin condensation or extremely dark, often fragmented, nuclei. Southern hybridization following agarose gel electrophoresis of DNA extracted from the developing cortex, but not from adult brain, showed a 'ladder' pattern which is typical of internucleosomal DNA fragmentation. Taken together these results show that naturally occurring cell death (programmed cell death) in the developing cerebral cortex has the morphology of apoptosis and is associated with endonuclease activation.

Increased expression of bcl-2 immunoreactivity in the developing cerebral cortex of the rat.

Bcl-2 proto-oncogene encodes a protein which may cancel the cell death programme in normal development and experimentally induced conditions. Strong bcl-2 immunoreactivity occurs in the neocortex and hippocampus of the developing rat during the 1st postnatal week. Bcl-2 immunoreactivity rapidly decreases from this age onwards to steady very low levels in adulthood. Since increased expression of bcl-2 immunoreactivity during cortical neurogenesis is coincidental in time with a special vulnerability of cortical neurons to naturally occurring cell death, it is suggested that bcl-2 may have a role in regulating cell death and survival during cortical morphogenesis.

Induction of HSP70 mRNA and HSP70 protein in the hippocampus of the developing gerbil following transient forebrain ischemia.

The effects of a 20-min transient episode of forebrain ischemia on the induction of HSP70 mRNA and protein, and the histopathological outcome in the hippocampus of the developing gerbil, were examined at postnatal days (P) 7, 15, 21 and 30 and in adulthood. 4 days after the ischemic episode, P7 gerbils did not show apparent histological abnormalities; however, from P15 onwards, ischemia resulted in necrosis in selected areas of the hippocampus. At P15 and P21, necrosis was observed in the base of the granular cell layer of the dentate gyrus and in the CA3 pyramidal cell layer, whereas at P30 and adult necrosis was apparent in the CA1 pyramidal cell layer. HSP70 mRNA induction was not found in ischemic P7 and P15 gerbils while, from P21 onwards, induction was observed in the dentate gyrus and CA1 pyramidal cell layer. In addition, at P30 and adult, HSP70 mRNA expression was also seen in CA3 pyramidal cell layer. Induction of HSP70 immunoreactivity was not seen at P7 but, from P15 onwards, ischemia induced HSP70 immunoreactivity in different areas: in dentate gyrus granular and molecular layers, from P15 onwards; in CA1 pyramidal cell layer, from P21 onwards; and in CA3 pyramidal cell layer, from P30 onwards. Results show selective age-dependent patterns of vulnerability to ischemia in the gerbil hippocampus which, overall, were not well-correlated to the corresponding HSP70 mRNA and protein induction patterns.

Stereotaxic administration of 1-methyl-4-phenylpyridinium ion (MPP+) decreases striatal fructose 2,6-bisphosphate in rats.

The stereotaxic administration of 1-methyl-4-phenylpyridinium ion (MPP+) into the neostriatum of male rats caused a lesion that resulted in a large dose-dependent loss of striatal fructose 2,6-bisphosphate; initial values were restored 5 days after the treatment. This effect was not protected by systemic administration of MK-801 or by nitroarginine. The content of hexose 6-phosphates and ATP was also reduced by MPP+ treatment, whereas lactate was increased. Biochemical and histological results suggested that MPP+ caused a nonselective cell death, followed by a pronounced astroglial response, parallel to fructose 2,6-bisphosphate recovery. The stereotaxic administration of rotenone showed a different time effect on fructose 2,6-bisphosphate cerebral content, with a significantly faster recovery. These results indicate that cerebral fructose 2,6-bisphosphate may be a sensitive metabolite related to brain damage caused by potent neurotoxins such as MPP+. On the other hand, they show that MPP+ acts in the brain through a quick, strong cytotoxic mechanism, which probably involves mechanisms other than mitochondrial chain blockage.