Andreas Kyrozis

Blockade of Gap Junctions In Vivo Provides Neuroprotection After Perinatal Global Ischemia

Background and Purpose— We investigated the contribution of gap junctions to brain damage and delayed neuronal death produced by oxygen-glucose deprivation (OGD). Methods— Histopathology, molecular biology, and electrophysiological and fluorescence cell death assays in slice cultures after OGD and in developing rats after intrauterine hypoxia-ischemia (HI). Results— OGD persistently increased gap junction coupling and strongly activated the apoptosis marker caspase-3 in slice cultures. The gap junction blocker carbenoxolone applied to hippocampal slice cultures before, during, or 60 minutes after OGD markedly reduced delayed neuronal death. Administration of carbenoxolone to ischemic pups immediately after intrauterine HI prevented caspase-3 activation and dramatically reduced long-term neuronal damage. Conclusions— Gap junction blockade may be a useful therapeutic tool to minimize brain damage produced by perinatal and early postnatal HI.

Diet, physical activity and cognitive impairment among elders : the EPIC-Greece cohort (European Prospective Investigation into Cancer and Nutrition)

OBJECTIVES To identify dietary and lifestyle variables that may affect cognitive function in the elderly. DESIGN Population-based prospective cohort study. SETTING General community residing in Athens and the surrounding Attica region of Greece. SUBJECTS A total of 732 men and women, 60 years or older, participating in the EPIC-Greece cohort (European Prospective Investigation into Cancer and Nutrition) and residing in the Attica region had sociodemographic, anthropometric, medical, dietary and lifestyle variables ascertained at enrolment (1993-1999). Six to 13 years later, cognitive function was evaluated through the Mini-Mental State Examination (MMSE) score and affective state through the Geriatric Depression Scale (GDS). RESULTS MMSE score was positively associated with years of formal education, height and physical activity and inversely with age, diabetes mellitus and GDS score (P < 0.05 for all). Among dietary variables, intake of PUFA was inversely associated with cognitive function and this association was largely accounted for by a similar association with seed oils. Adherence to the Mediterranean diet, as well as intake of olive oil, MUFA and SFA exhibited weakly positive but not significant associations. CONCLUSION Physical activity and early life factors as reflected in height are significant predictors of cognitive function in the elderly. Seed oil consumption may adversely affect cognition, whereas other nutritional factors do not appear to have a quantitatively large effect.

Smoking and risk for amyotrophic lateral sclerosis: Analysis of the EPIC cohort

Cigarette smoking has been reported as “probable” risk factor for Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of aetiology. The extensive longitudinal data of the European Prospective Investigation into Cancer and Nutrition (EPIC) were used to evaluate age‐specific mortality rates from ALS and the role of cigarette smoking on the risk of dying from ALS.

Reproductive factors and exogenous hormone use in relation to risk of glioma and meningioma in a large European cohort study

Background: The etiologies of glioma and meningioma tumors are largely unknown. Although reproductive hormones are thought to influence the risk of these tumors, epidemiologic data are not supportive of this hypothesis; however, few cohort studies have published on this topic. We examined the relation between reproductive factors and the risk of glioma and meningioma among women in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: After a mean of 8.4 years of follow-up, 193 glioma and 194 meningioma cases were identified among 276,212 women. Information on reproductive factors and hormone use was collected at baseline. Cox proportional hazard regression was used to determine hazard ratios (HR) and 95% confidence intervals (95% CI). Results: No associations were observed between glioma or meningioma risk and reproductive factors, including age at menarche, parity, age at first birth, menopausal status, and age at menopause. A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR, 1.79; 95% CI, 1.18-2.71) compared with never users. Similarly, current users of oral contraceptives were at higher risk of meningioma than never users (HR, 3.61; 95% CI, 1.75-7.46). Conclusion: Our results do not support a role for estrogens and glioma risk. Use of exogenous hormones, especially current use, seems to increase meningioma risk. However, these findings could be due to diagnostic bias and require confirmation. Impact: Elucidating the role of hormones in brain tumor development has important implications and needs to be further examined using biological measurements. Cancer Epidemiol Biomarkers Prev; 19(10); 2562–9. ©2010 AACR.

Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis: The EPIC cohort

Objectives: The aim of this study was to investigate for the first time the association between body fat and risk of amyotrophic lateral sclerosis (ALS) with an appropriate prospective study design. Methods: The EPIC (European Prospective Investigation into Cancer and Nutrition) study included 518,108 individuals recruited from the general population across 10 Western European countries. At recruitment, information on lifestyle was collected and anthropometric characteristics were measured. Cox hazard models were fitted to investigate the associations between anthropometric measures and ALS mortality. Results: Two hundred twenty-two ALS deaths (79 men and 143 women) occurred during the follow-up period (mean follow-up = 13 years). There was a statistically significant interaction between categories of body mass index and sex regarding ALS risk (p = 0.009): in men, a significant linear decrease of risk per unit of body mass index was observed (hazard ratio = 0.93, 95% confidence interval 0.86–0.99 per kg/m2); among women, the risk was more than 3-fold increased for underweight compared with normal-weight women. Among women, a significant risk reduction increasing the waist/hip ratio was also evident: women in the top quartile had less than half the risk of ALS compared with those in the bottom quartile (hazard ratio = 0.48, 95% confidence interval 0.25–0.93) with a borderline significant p value for trend across quartiles (p = 0.056). Conclusion: Increased prediagnostic body fat is associated with a decreased risk of ALS mortality.

Dietary and lifestyle variables in relation to incidence of Parkinson’s disease in Greece

Identification of dietary and lifestyle variables associated with the development of Parkinson’s disease (PD) may offer pathogenetic clues and prevention opportunities. In a population-based prospective cohort study, 26,173 participants in the EPIC–Greece cohort had sociodemographic, anthropometric, medical, dietary and lifestyle variables ascertained at enrolment and periodically reassessed with follow-up contacts. Based on these data, subjects were screened as possible PD cases if they (1) reported either a medical diagnosis of PD or use of anti-PD drugs and (2) did not report preceding causes of secondary parkinsonism. For diagnostic validation, possible incident PD cases were assessed by a focused 3-item telephone questionnaire. Cox proportional hazards regression was used to evaluate associations between potential predictors and incident PD. The main multivariate model included gender, age, marital status, schooling years, farming occupation, smoking status, caffeinated coffee, body mass index, physical activity and energy intake. Additional models included all above variables plus one dietary item at a time. Incidence rate adjusted to the European population was 16.9 per 100,000 person-years. In multivariate models, incident PD exhibited strong positive association with consumption of milk, but not cheese or yoghurt. This finding may help narrow down the search for potential dairy product components with a facilitatory role in PD. Concerning other dietary components, inverse association was found between polyunsaturated fat intake and incident PD. Also, inverse association was found with tobacco smoking, in line with previous studies, but not with caffeine.

Dietary lipids and geriatric depression scale score among elders: The EPIC-Greece cohort

In a prospective epidemiological investigation aiming to identify dietary lipids potentially associated with affective state and depression, 610 healthy men and women aged 60 years or older, participating in the EPIC-Greece cohort and residing in the Attika region had dietary, sociodemographic, anthropometric, medical and lifestyle variables ascertained at enrollment. Six to 13 years later, affective state was evaluated through the 15-point geriatric depression scale (GDS) score along with cognitive function and medical variables. In multivariate linear regression analysis, while adjusting for potential confounders, GDS score was negatively associated with dietary intake of monounsaturated lipids (MUFA) and their main source, olive oil, and positively associated with intake of polyunsaturated lipids (PUFA) and one of their principal sources, seed oils. Intake of calories, total lipids, fish and seafood or saturated lipids did not exhibit significant association with GDS. Potential non-linearities were assessed by quantile multivariate regression analysis: The median GDS score was positively associated with PUFA and seed oils intake, while other lipid groups showed no appreciable associations. The 90th percentile of the GDS score (towards the high end) exhibited significant negative associations with MUFA and olive oil, weaker positive associations with PUFA and seed oils and no appreciable association with other lipid group dietary intakes. We conclude that among Attika elders, lower intake of seed oils and higher intake of olive oil prospectively predict a healthier affective state. Olive oil intake, in particular, predicts a lower chance of scoring in the highest part of the GDS.

Coffee and tea intake and risk of brain tumors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study

BACKGROUND In a recent US cohort study, total coffee and tea consumption was inversely associated with risk of glioma, and experimental studies showed that caffeine can slow the invasive growth of glioblastoma. OBJECTIVE The objective was to examine the relation between coffee and tea intake and the risk of glioma and meningioma in a large European cohort study, the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN Data on coffee and tea intake were collected from men and women recruited into the EPIC cohort study. Over an average of 8.5 y of follow-up, 343 cases of glioma and 245 cases of meningioma were newly diagnosed in 9 countries. We used Cox proportional hazards models to examine the relation between coffee and tea and brain tumors. RESULTS We observed no associations between coffee, tea, or combined coffee and tea consumption and risk of either type of brain tumor when using quantiles based on country-specific distributions of intake. However, a significant inverse association was observed for glioma risk among those consuming ≥100 mL coffee and tea per day compared with those consuming <100 mL/d (hazard ratio: 0.66; 95% CI: 0.44, 0.97; P = 0.03). The association was slightly stronger in men (hazard ratio: 0.59; 95% CI: 0.34, 1.01) than in women (hazard ratio: 0.74; 95% CI: 0.42, 1.31), although neither was statistically significant. CONCLUSIONS In this large cohort study, we observed an inverse association between total coffee and tea consumption and risk of glioma that was consistent with the findings of a recent study. These findings, if further replicated in other studies, may provide new avenues of research on gliomas.

Anthropometric Measures, Physical Activity, and Risk of Glioma and Meningioma in a Large Prospective Cohort Study

Body fatness has been associated with increased risk of a number of hormone-dependent cancers. Recent studies suggest that body mass index (BMI) may be related to meningiomas, which are more common in women than men, and for which estrogens are believed to play a role. Using data from a large European propective cohort, 203 incident cases of meningioma and 340 cases of glioma were included in the analysis for measures of body fat, height, and physical activity among 380,775 participants. All analyses were conducted using Cox proportional hazards model and controlling for age, sex, country, and education. A 71% increase in risk of meningioma was observed among men and women in the top quartile of waist circumference (HR = 1.71, 95% CI = 1.08–2.73, Ptrend = 0.01). A positive association was also observed for BMI and meningioma (HR = 1.48, 95% CI = 0.98–2.23, for BMI ≥30 compared with a BMI of 20–24.9, Ptrend = 0.05). An association with height and meningioma was also suggestive (HR = 1.24, 95% 0.96–1.51, for each 10 cm increase). In contrast, no associations were observed for height and different measures of body fat and risk of glioma. Physical activity was not related to either type of brain tumors. Results from this study support an increase in risk of meningioma with higher body fatness among both men and women. No association was observed between anthropometric measures and risk of glioma. Cancer Prev Res; 4(9); 1385–92. ©2011 AACR.

Proinflammatory cytokines in serum and cerebrospinal fluid of CIDP patients

Abstract Introduction: Little is known about the role of cytokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Interleukin (IL)-12 and IL-15 are the major growth and differentiation factors for Th-1 cells and IL-17 is a marker of Th-17 cell expansion and activation, a high proinflammatory new subset of T cells that induce severe autoimmunity. Patients and methods: We measured by enzyme-like immunosorbent assay serum and cerebrospinal fluid (CSF) levels of IL-15, IL-12, and IL-17 in 24 patients with CIDP and 12 patients with other non-inflammatory neurological disorders and serum levels in 16 healthy subjects. Results: We found a positive association of CSF IL-12 (P = 0·012) with CIDP presence (P<0·001). Conclusions: Our findings suggest that IL-12 may be involved as potential marker of immune activation in CIDP. The increase in its levels in CSF may be a marker of initiation of Th-1 cell-mediated immunity.