Brain-derived neurotrophic factor expression after acute administration of ethanol

Earlier findings suggest that, in addition to its well-known neurotrophic role, brain-derived neurotrophic factor (BDNF) is also involved in the rewarding and reinforcing effects of drugs of abuse. The purpose of the present study was to examine the effects of acute administration of ethanol (1.25 or 2.5 g/kg i.p.) on the expression profile of BDNF in the rat brain by determining the BDNF mRNA expression in the frontal cortex, nucleus accumbens, amygdala, hippocampus, and ventral tegmental area. Ethanol decreased BDNF mRNA levels dose-dependently in the hippocampus, and after the higher ethanol dose in the frontal cortex, nucleus accumbens and amygdala, while increasing them in the ventral tegmental area. Furthermore, BDNF mRNA expression was found to be regulated in a temporally different manner in all investigated brain areas. These data suggest that BDNF is involved in the acute effects of ethanol, but separate brain areas may be differentially engaged in the mediation of these effects.     

Metamers of the ventral stream

The human capacity to recognize complex visual patterns emerges in a sequence of brain areas known as the ventral stream, beginning with primary visual cortex (V1). We developed a population model for mid-ventral processing, in which nonlinear combinations of V1 responses are averaged in receptive fields that grow with eccentricity. To test the model, we generated novel forms of visual metamers, stimuli that differ physically but look the same. We developed a behavioral protocol that uses metameric stimuli to estimate the receptive field sizes in which the model features are represented. Because receptive field sizes change along the ventral stream, our behavioral results can identify the visual area corresponding to the representation. Measurements in human observers implicate visual area V2, providing a new functional account of neurons in this area. The model also explains deficits of peripheral vision known as crowding, and provides a quantitative framework for assessing the capabilities and limitations of everyday vision.     

Association of sleep duration with weight and weight gain: a prospective follow-up study

The objective of this study was to examine the associations of sleep duration with subsequent weight and major weight gain in women and men during a follow-up period of 5-7years. The data were derived from the Helsinki Health Study cohort mail questionnaire surveys among 40-60-year-old employees of the City of Helsinki, Finland. At baseline in 2000-2002, 8960 people responded to the survey (80% women, response rate 67%). The follow-up survey was conducted in 2007 among all respondents to the baseline survey (n=7332, response rate 83%). Sleep duration (5h or less up to 10h or more) and weight and weight gain of at least 5kg were based on self-reports. Analyses of variance and logistic regression analyses were used to examine the associations between sleep duration and weight, as well as major weight gain. Short sleep duration was associated with major weight gain [odds ratio (OR) 1.52; 95% confidence interval (CI) 1.08, 2.14] during the follow-up. Adjusting for several covariates had only minor effects on that association. Long sleep duration was associated with major weight gain after adjusting for age (OR 1.35; 95% CI 1.00-1.81). No associations were found among men. Sleep duration was associated with major weight gain among middle-aged employed women. Short sleep may be a risk factor for subsequent weight gain.     

Oral health in predialysis patients with emphasis on diabetic nephropathy

We investigated oral health of chronic kidney disease (CKD) patients at predialysis state. The hypothesis was that diabetic nephropathy affects oral health more detrimentally than other CKD patients due to the known risk diabetes presents in this regard. We expected worse oral health and particularly poor periodontal health among the diabetic patients. A cross-sectional study was conducted in the Helsinki University Central Hospital, Finland, on 148 patients with different kinds of kidney disease at predialysis state. Data from medical records, clinical oral examination, saliva, and mucosal yeast counts were analyzed and compared between the disease groups. Of the patients, 53 (36%) had diabetic nephropathy (29 patients with type 1, 24 patients with type 2 diabetes). Compared with other CKD patients, diabetic patients had poor glycemic control as expected (mean HbA_1C 8.0% vs 5.9%, p < 0.01). Diabetic patients also had more dental caries (mean number of carious teeth 5.1 vs 3.1, p < 0.01) and lower salivary flow rates than other CKD patients (stimulated salivary flow 1.2 ml/min vs 1.6 ml/min, p < 0.05). No difference between groups was observed in periodontal health and yeast counts. In conclusion, diabetic nephropathy patients indeed had worse dental health in comparison to CKD group. However, contrary to our expectation, diabetic nephropathy did not seem to affect periodontal health more severely than the other kidney diseases.     

ATG16L1 gene polymorphisms are associated with palmoplantar pustulosis

Genes in autophagy pathway play an important role in innate and adaptive immunity. The aim of the study was to assess the impact of ATG16L1 gene on susceptibility of palmoplantar pustulosis. Four single nucleotide polymorphisms (SNPs) within the ATG16L1 region (rs2241880, rs2241879, rs7587633, and rs13005285) were genotyped in 241 control subjects and 38 palmoplantar pustulosis (PPP) patients of Estonian descent. The data analysis revealed a significantly higher frequency distribution of the rs2241880 G (odds ratio [OR] = 1.88, p = 0.0073) and rs2241879 A (OR = 1.87, p = 0.0079) allele in the PPP group when compared with the control group. The frequency distribution of the GACG haplotype was significantly higher (OR = 1.82, p = 0.016) in the PPP group when compared with the control group. The current study provides evidence of an association of the ATG16L1 gene in susceptibility to palmoplantar pustulosis, and supports the notion that the ATG16L1 gene as a member of the autophagy pathway most likely plays an important role in immune response.     

Association between type 2 diabetes and exposure to persistent organic pollutants

OBJECTIVE

The prevalence of type 2 diabetes is increasing alarmingly in both developed and developing countries. Recently, exposure to persistent organic pollutants (POPs) has been associated with the prevalence of type 2 diabetes. The purpose of this cross-sectional study is to examine the association between type 2 diabetes and POP exposure in the Helsinki Birth Cohort Study.

RESEARCH DESIGN AND METHODS

The cohort consists of 8,760 people born in Helsinki during 1934–1944, before the global POP emission peak. In 2003, a clinical examination was performed, including blood sampling for laboratory analyses of serum lipids and POPs. Complete data from the examination were available for 1,988 participants. The concentrations of each POP were categorized into four groups on the basis of percentile intervals, and logistic regression was performed to examine diabetes prevalence across the POP categories, adjusting for sex, age, waist circumference, and mean arterial pressure and using the lowest category as the reference group.

RESULTS

Among the participants with the highest exposure to oxychlordane, trans-nonachlor, 1,1-dichloro-2,2-bis-(p-chlorophenyl)-ethylene (p,p’-DDE, and polychlorinated biphenyl 153, the risk of type 2 diabetes was 1.64–2.24 times higher than that among individuals with the lowest exposure (P_lin = 0.003–0.050, where P_lin is the P value for linear trend across POP categories). In the stratified analysis, the associations between type 2 diabetes and oxychlordane and trans-nonachlor remained significant and were strongest among the overweight participants. Exposure to 2,2′,4,4′-tetrabromodiphenyl ether (BDE 47) and 2,2′,4,4′,5,5′-hexabromodiphenyl ether (BDE 153) was not associated with type 2 diabetes.

CONCLUSIONS

This study confirms the association between type 2 diabetes and adult-only exposure to organochlorine pesticides in a general urban population.The prevalence of type 2 diabetes is increasing alarmingly in both developed and developing countries. The disease has traditionally been regarded as a multifactorial disorder, with a strong genetic component and lifestyle influences. Lately, it has been suggested that, in addition to the conventional risk factors, which include genetic susceptibility, obesity, physical inactivity, and an unhealthy diet, environmental factors may have a significant contribution. Specifically, exposure to persistent organic pollutants (POPs) has been shown to have a strong positive association with type 2 diabetes and related metabolic conditions (1–8).POPs are a diverse group of ubiquitous environmental contaminants, characterized by toxicity, slow degradation, lipid solubility, and accumulation in the food chain. In numerous cross-sectional studies performed during the last decade, associations between type 2 diabetes and exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), brominated flame retardants (polybrominated diphenylethers [PBDEs]), and some organochlorine pesticides (OCPs) were observed (1–8). So far, the strongest indications regarding the positive association between POPs and type 2 diabetes within the general population have been obtained from a cross-sectional study in the U.S. (the National Health and Nutrition Examination Survey [NHANES]) (5–7). Lee et al. (5) observed that the prevalence of type 2 diabetes among the most exposed subgroup was 38 times higher than that among the least exposed group. It is striking that obesity was found to be a risk factor for type 2 diabetes and insulin resistance only in association with increased concentrations of POPs (5). The association between POPs and impaired glucose regulation was confirmed in in vitro and in vivo (9–11) studies.Human exposure to the majority of POPs occurs mainly through diet and, especially, foods of animal origin. In Finland, the most important source of POPs is Baltic Sea fatty fish, such as Baltic herring (Clupea harengus membras) and salmon (Salmo salar) (12). Although human exposure to POPs such as PCDD/Fs and PCBs in the Baltic region has been declining during the last 3 decades (13), these compounds are still detectable in human samples. In contrast to PCDD/Fs and PCBs, the concentrations of many emerging chemicals that hold a potential for health threat such as PBDEs, which are widely used as flame retardants, have recently increased in humans (14). POPs are persistent in the body, and measurements from serum are assumed to reflect lifetime exposure.The purpose of the present cross-sectional study is to examine the association between type 2 diabetes and POP exposure in the Helsinki Birth Cohort Study, which represents a general adult urban Finnish population. The cohort consists of people who were born in the 1930s and 1940s, well before the global POP emissions peaked, and their exposure during the fetal and childhood period has probably been very low. However, during their adulthood, they experienced a steep increase in environmental POP concentrations (15). Therefore, this population provides an excellent opportunity to study the association between adult exposure to POPs and type 2 diabetes.     

Economic difficulties and subsequent sleep problems: evidence from British and Finnish occupational cohorts

BackgroundSocial determinants of sleep may prove to be as important as health status. In this study we examined the extent to which persistent and changing economic difficulties are associated with sleep problems in two prospective occupational cohorts.MethodsWe used data from Finnish (baseline 2000–2002; follow-up 2007; n = 6328) and British (baseline 1997–1999; follow-up 2003–2004; n = 5002) public sector employees. Economic difficulties, sleep problems, and a variety of covariates were assessed at baseline and follow-up.ResultsPrevalence of frequent sleep problems at follow-up was 27% and 20% among women and men in the Finnish cohort, and 34% and 27% in the British cohort, respectively. Odds for sleep problems were higher among those with persistent economic difficulties (frequent economic difficulties at baseline and follow-up) compared to those with no difficulties. This association remained after multiple adjustments, including parental and current socioeconomic position, in the Finnish (OR 1.72, 95% CI 1.35–2.18) cohort. Increases in economic difficulties were similarly associated with sleep problems in the Finnish and the British cohort.ConclusionEvidence from two occupational cohorts suggests strong associations between economic difficulty and poor sleep. Awareness of this association will help health care professionals identify and prevent sleep problems.     

Cathepsin K deficiency aggravates lung injury in hyperoxia-exposed newborn mice

Cathepsin K (CatK) is a potent collagenase and elastase and may be involved in the development of neonatal bronchopulmonary dysplasia. The authors evaluated the effects of CatK deletion on neonatal lung development and response to prolonged hyperoxic challenge. CatK deficiency resulted in thinner alveolar walls than wild-type littermates on postnatal day (PN) 7. However, no morphological difference could be detected between CatK-deficient and control groups on PN 14. Exposure to 90% oxygen for 7 days after birth caused intensive CatK expression in the bronchial epithelium and alveolar macrophages of wild-type mice. Hyperoxia caused fatal respiratory distress in both groups of mice. However, whereas ～20% of wild-type mice survived for 2 weeks in hyperoxia, all CatK-deficient mice died within the first 9 postnatal days. Hyperoxia-exposed lungs of CatK-deficient mice contained high number of macrophages and multinucleated giant cells and had increased content of reduced glutathione, indicating intensified pulmonary oxidative stress. These results suggest that CatK is involved in pulmonary development and it may be an important host-defence protease in the oxygen-stressed newborn lung.