Association between degenerative aortic valve disease and long-term exposure to cardiovascular risk factors: results of the longitudinal population-based KORA/MONICA survey

Degenerative aortic valve disease (DAVD), a common finding in the elderly, is associated with an increased risk of death due to cardiovascular causes. Taking advantage of its longitudinal design, this study evaluates the prevalence of DAVD and its temporal associations with long-term exposure to cardiovascular risk factors in the general population. We studied 953 subjects (aged 25-74 years) from a random sample of German residents. Risk factors had been determined at a baseline investigation in 1994/95. At a follow-up investigation, 10 years later, standardized echocardiography determined aortic valve morphology and aortic valve area (AVA) as well as left ventricular geometry and function. At the follow-up study, the overall prevalence of DAVD was 28%. In logistic regression models adjusting for traditional cardiovascular risk factors at baseline age (OR 2.0 [1.7-2.3] per 10 years, P < 0.001), active smoking (OR 1.7 [1.1-2.4], P = 0.009) and elevated total cholesterol levels (OR 1.2 [1.1-1.3] per increase of 20 mg/dL, P < 0.001) were significantly related to DAVD at follow-up. Furthermore, age, baseline status of smoking, and total cholesterol level were significant predictors of a smaller AVA at follow-up study. In contrast, hypertension and obesity had no detectable relationship with long-term changes of aortic valve structure. In the general population we observed a high prevalence of DAVD that is associated with long-term exposure to elevated cholesterol levels and active smoking. These findings strengthen the notion that smoking cessation and cholesterol lowering are promising treatment targets for prevention of DAVD.

Respiratory infection, exposure to mouse allergen and breastfeeding: role in recurrent wheezing in early life

Background: Environmental factors may influence the development of allergen sensitization and asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life as a risk factor for recurrent wheezing. Methods: One hundred and four infants from low-income families, at high risk of asthma, were enrolled at birth. Dust samples were collected from the bedding and bedroom floor within 6 months after birth. Recurrent wheezing was defined as 3 or more wheezing episodes in the past year. Endotoxin was determined by Limulus amebocyte lysate assay, and major indoor allergens were quantitated by ELISA in dust extracts. IgE antibodies were measured by ImmunoCAP at 30 months of age. Results: At 30 months, 51 of the 99 infants who completed the study (51.5 per cent) had recurrent wheezing. Respiratory infection was strongly associated with recurrent wheezing (OR 6.67, 95 per cent CI 1.96-22.72), whereas exclusive breastfeeding for at least 1 month was a protective factor (OR 0.09, 95 per cent CI 0.01-0.51). Exposure to high levels of mouse allergen was more frequent among non-recurrent wheezers, approaching significance (OR 0.12, 95 per cent CI 0.01-1.13; p = 0.064). None of the children were sensitized to mouse. Sensitization to mite was found in 26/90 (28.8 per cent) children, with no association with recurrent wheezing. Conclusion: Respiratory infection was strongly associated with recurrent wheezing in the first 30 months of life, in children at high risk of asthma, living in a socially deprived community in Brazil

Environmental Exposure to Methylmercury is Associated with a Decrease in Nitric Oxide Production

Some studies have recently suggested that mercury (Hg)-exposed populations face increased risks of cardiovascular diseases, and experimental data indicate that such risks might be due to reductions in nitric oxide bioavailability. However, no previous study has examined whether Hg exposure affects plasma nitrite concentrations in humans as an indication of nitric oxide production. Here, we investigated whether there is an association between circulating nitrite and Hg concentrations in whole blood, plasma and hair from an exposed methylmercury (MeHg) population. Hair and blood samples were collected from 238 persons exposed to MeHg from fish consumption. Hg concentrations in plasma (PHg), whole blood (BHg) and hair Hg (HHg) were determined by inductively coupled plasma-mass spectrometry. Mean BHg content was 49.8 +/- 35.2 mu g/l, mean PHg was 7.8 +/- 6.9 mu g/l and HHg 14.6 +/- 10.6 mu g/g. Mean plasma nitrite concentration was 253.2 +/- 105.5 nM. No association was found between plasma nitrite concentration and BHg or HHg concentrations in a univariate model. However, multiple regression models adjusted for gender, age and fish consumption showed a significant association between plasma nitrite and plasma Hg concentration (beta = -0.1, p < 0.001). Our findings constitute preliminary clinical evidence that exposure to MeHg may cause inhibitory effects on the production of endothelial nitric oxide.

Sub-Chronic Exposure to Methylmercury at Low Levels Decreases Butyrylcholinesterase Activity in Rats

In this study, we examined the effects of low levels and sub-chronic exposure to methylmercury (MeHg) on butyrylcholinesterase (BuChE) activity in rats. Moreover, we examined the relationship between BuChE activity and oxidative stress biomarkers [delta-aminolevulinic acid dehydratase (delta-ALA-D) and malondialdehyde levels (MDA)] in the same animals. Rats were separated into three groups (eight animals per group): (Group I) received water by gavage; (Group II) received MeHg (30 mu g/kg/day) by gavage; (Group III) received MeHg (100 mu g/kg/day). The time of exposure was 90 days. BuChE and ALA-D activities were measured in serum and blood, respectively; whereas MDA levels were measured in plasma. We found BuChE and ALA-D activities decreased in groups II and III compared to the control group. Moreover, we found an interesting negative correlation between plasmatic BuChE activity and MDA (r = -0.85; p < 0.01) and a positive correlation between plasmatic BuChE activity and ALA-D activities (r = 0.78; p < 0.01), thus suggesting a possible relationship between oxidative damage promoted by MeHg exposure and the decrease of BuChE activity. In conclusion, long-term exposure to low doses of MeHg decreases plasmatic BuChE activity. Moreover, the decrease in the enzyme is strongly correlated with the oxidative stress promoted by the metal exposure. This preliminary finding highlights a possible mechanism for MeHg to reduce BuChE activity in plasma. Additionally, this enzyme could be an auxiliary biomarker on the evaluation of MeHg exposure.

Low level and sub-chronic exposure to methylmercury induces hypertension in rats: nitric oxide depletion and oxidative damage as possible mechanisms

Increased risk of hypertension after methylmercury (MeHg) exposure has been suggested. However, the underlying mechanisms are not well explored. In this paper, we have analyzed whether sub-chronic exposure to MeHg increases systolic blood pressure even at very low levels. In addition, we analyzed if the methylmercury-induced hypertension is associated with a decreased plasmatic nitric oxide levels and with a dysregulation of the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), as well as the levels of MDA and glutathione. For this study, Wistar rats were treated with methylmercury chloride (100 mu g/kg per day) or vehicle. Total treatment time was 100 days. Malondialdehyde (MDA) and circulating NOx levels and superoxide dismutase (SOD) and catalase (CAT) activities were determined in plasma, whereas glutathione levels were determined in erythrocytes. Our results show that long-term treatment at a low level of MeHg affected systolic blood pressure, increasing and reducing the levels of plasmatic MDA and NOx, respectively. However, the activity of SOD did not decrease in the MeHg exposed group when compared to the control. We found a negative correlation between plasmatic nitrite/nitrate (NOx) levels and systolic blood pressure (r = -0.67; P = 0.001), and a positive correlation between MDA and systolic blood pressure (r = 0.61; P = 0.03), thus suggesting increased inhibition of NO formation with the increase of hypertension. In conclusion, long-term exposure to a low dose of MeHg increases the systolic pressure and is associated, at least in part, with increased production of ROS as judged by increased production of malondialdehyde and depressed NO availability.

THE ANTERIOR CINGULATE CORTEX IS A TARGET STRUCTURE FOR THE ANXIOLYTIC-LIKE EFFECTS OF BENZODIAZEPINES ASSESSED BY REPEATED EXPOSURE TO THE ELEVATED PLUS MAZE AND FOS IMMUNOREACTIVITY

Prior experience with the elevated plus maze (EPM) increases the avoidance of rodents to the open arms and impairs the anxiolytic-like effects of benzodiazepines on the traditional behaviors evaluated upon re-exposure to the maze, a phenomenon known as one-trial tolerance. Risk assessment behaviors are also sensitive to benzodiazepines. During re-exposure to the maze, these behaviors reinstate the information-processing initiated during the first experience, and the detection of danger generates stronger open-arm avoidance. The present study investigated whether the benzodiazepine midazolam alters risk assessment behaviors and Fos protein distribution associated with test and retest sessions in the EPM. Naive or maze-experienced Wistar rats received either saline or midazolam (0.5 mg/kg i.p.) and were subjected to the EPM. Midazolam caused the usual effects on exploratory behavior, increasing exploratory activity of naive rats in the open arms and producing no effects on these conventional measures in rats re-exposed to the maze. Risk assessment behaviors, however, were sensitive to the benzodiazepine during both sessions, indicating anxiolytic-like effects of the drug in both conditions. Fos immunohistochemistry showed that midazolam injections were associated with a distinct pattern of action when administered before the test or retest session, and the anterior cingulate cortex, area 1 (Cg1), was the only structure targeted by the benzodiazepine in both situations. Bilateral infusions of midazolam into the Cg1 replicated the behavioral effects of the drug injected systemically, suggesting that this area is critically involved in the anxiolytic-like effects of benzodiazepines, although the behavioral strategy adopted by the animals appears to depend on the previous knowledge of the threatening environment. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

Chronic exposure to fine particulate matter emitted by traffic affects reproductive and fetal outcomes in mice

Air pollution is an important environmental health risk factor that can result in many different gestational and reproductive negative outcomes. In this study, we have investigated the effects of two different times of exposure (before conception and during pregnancy) to urban ambient particulate matter on reproductive and pregnancy outcomes in mice. Using exposure chambers receiving filtered (F) and non-filtered (NF) air, we observed that exposed females exhibited changes in the length of estrus cycle and extended estrus and, therefore, a reduction in the number of cycles during the studied period (F2.6 +/- 0.22 and NF 1.2 +/- 0.29, p = 0.03). The mean number of antral follicles declined by 36% (p = 0.04) in NF mice (75 +/- 35.2) compared to F mice (118.6 +/- 18.4). our results further indicate a significant increase in time necessary for mating and decreased fertility and pregnancy indices (p = 0.003) in NF couples. Mean post-implantation loss rates were increased by 70% (p <= 0.005) in the NF2 group (exposed before and during pregnancy to NF air) compared to the F1 group (exposed before and during pregnancy to F air) and were influenced by both pre-gestational (p < 0.004) and gestational (p < 0.01) period exposure. Fetal weight was significantly higher in the F1 group when compared with the other groups (p < 0.001), at a 20% higher weight in the F1 group (0.86 +/- 0.18 g) than in the NF2 group (0.68 +/- 0.10g). Furthermore, fetal weight was influenced by both pre-gestational and gestational period exposure, and a significant interaction between these two factors was found (p < 0.001). This study demonstrated that exposure to ambient levels of urban traffic-generated particulate matter negatively affects different functions and stages of the reproductive process. Our results also reinforce the idea that maternal exposure to air pollution is linked to negative pregnancy outcomes, even if the exposure occurs only before conception. (C) 2009 Elsevier Inc. All rights reserved.

Impact of short-term preconceptional exposure to particulate air pollution on treatment outcome in couples undergoing in vitro fertilization and embryo transfer (IVF/ET)

To assess the potential effects of short-term exposure to particulate air pollution during follicular phase on clinical, laboratory, and pregnancy outcomes of women undergoing IVF/ET. Retrospective cohort study of 400 first IVF/ET cycles of women exposed to ambient particulate matter during follicular phase. Particulate matter (PM) was categorized into quartiles (Q(1): a parts per thousand currency sign30.48 A mu g/m(3), Q(2): 30.49-42.00 A mu g/m(3), Q(3): 42.01-56.72 A mu g/m(3), and Q(4): > 56.72 A mu g/m(3)). Clinical, laboratory, or treatment variables were not affected by follicular phase PM exposure periods. Women exposed to Q(4) period during the follicular phase of conception cycles had a higher risk of miscarriage (odds ratio, 5.05; 95% confidence interval: 1.04-25.51) when compared to women exposed to Q(1-3) periods. Our results show an association between brief exposure to high levels of ambient PM during the preconceptional period and early pregnancy loss, although no effect of this exposure on clinical, laboratory, and treatment outcomes was observed.

Homocysteine and cysteine concentrations are modified by recent exposure to environmental air pollution in Sao Paulo, Brazil

Millions of people worldwide are affected by anthropogenic air pollution derived from the combustion of fossil fuels. In this work, we tested the effects of fetal, lactation and post-weaning ambient air pollution exposure on total homocysteine (tHcy) concentrations and on a downstream pathway element, the plasma cysteine (Cys) concentration. Two similar exposure chambers (polluted and filtered chamber) were located near an area with heavy traffic in Sao Paulo, Brazil, and male Swiss mice were housed there from the pre-natal period until 3 months of age. Groups during fetal, lactation and adult periods of exposure were apportioned, and tHcy and Cys plasma concentrations were assessed when the animals were 3 months old. In our study, both the tHcy and Cys concentrations were decreased in groups that spent their final stage of life in polluted chambers, suggesting recent alterations in tHcy and Cys concentrations due to air pollution exposure. The possible relationship of these data with cardiovascular dysfunction is still a matter of controversy in animals; nevertheless, epigenetic mechanisms emerge as a possible issue to consider in the investigation of the link between air pollution and Hcy measurement. (C) 2009 Elsevier Inc. All rights reserved.

Respiratory Infection, Exposure to Mouse Allergen and Breastfeeding: Role in Recurrent Wheezing in Early Life

Background: Environmental factors may influence the development of allergen sensitization and asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life as a risk factor for recurrent wheezing. Methods: One hundred and four infants from low-income families, at high risk of asthma, were enrolled at birth. Dust samples were collected from the bedding and bedroom floor within 6 months after birth. Recurrent wheezing was defined as 3 or more wheezing episodes in the past year. Endotoxin was determined by Limulus amebocyte lysate assay, and major indoor allergens were quantitated by ELISA in dust extracts. IgE antibodies were measured by ImmunoCAP at 30 months of age. Results: At 30 months, 51 of the 99 infants who completed the study (51.5%) had recurrent wheezing. Respiratory infection was strongly associated with recurrent wheezing (OR 6.67, 95% CI 1.96-22.72), whereas exclusive breastfeeding for at least 1 month was a protective factor (OR 0.09, 95% CI 0.01-0.51). Exposure to high levels of mouse allergen was more frequent among non-recurrent wheezers, approaching significance (OR 0.12, 95% CI 0.01-1.13; p=0.064). None of the children were sensitized to mouse. Sensitization to mite was found in 26/90 (28.8%) children, with no association with recurrent wheezing. Conclusion: Respiratory infection was strongly associated with recurrent wheezing in the first 30 months of life, in children at high risk of asthma, living in a socially deprived community in Brazil. Copyright (C) 2009 S. Karger AG, Basel

AMYGDALAR ROLES DURING EXPOSURE TO A LIVE PREDATOR AND TO A PREDATOR-ASSOCIATED CONTEXT

The amygdala plays a critical role in determining the emotional significance of sensory stimuli and the production of fear-related responses. Large amygdalar lesions have been shown to practically abolish innate defensiveness to a predator; however, it is not clear how the different amygdalar systems participate in the defensive response to a live predator. Our first aim was to provide a comprehensive analysis of the amygdalar activation pattern during exposure to a live cat and to a predator-associated context. Accordingly, exposure to a live predator up-regulated Fos expression in the medial amygdalar nucleus (MEA) and in the lateral and posterior basomedial nuclei, the former responding to predator-related pheromonal information and the latter two nuclei likely to integrate a wider array of predatory sensory information, ranging from olfactory to non-olfactory ones, such as visual and auditory sensory inputs. Next, we tested how the amygdalar nuclei most responsive to predator exposure (i.e. the medial, posterior basomedial and lateral amygdalar nuclei) and the central amygdalar nucleus (CEA) influence both unconditioned and contextual conditioned anti-predatory defensive behavior. Medial amygdalar nucleus lesions practically abolished defensive responses during cat exposure, whereas lesions of the posterior basomedial or lateral amygdalar nuclei reduced freezing and increased risk assessment displays (i.e. crouch sniff and stretch postures), a pattern of responses compatible with decreased defensiveness to predator stimuli. Moreover, the present findings suggest a role for the posterior basomedial and lateral amygdalar nuclei in the conditioning responses to a predator-related context. We have further shown that the CEA does not seem to be involved in either unconditioned or contextual conditioned anti-predatory responses. Overall, the present results help to clarify the amygdalar systems involved in processing predator-related sensory stimuli and how they influence the expression of unconditioned and contextual conditioned anti-predatory responses. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of adolescent exposure to cocaine on locomotor activity and extracellular dopamine and glutamate levels in nucleus accumbens of DBA/2J mice

Adolescents differ from adults in their acute sensitivity to several drugs of abuse, but little is known about the long-term neurobehavioral effects of adolescent drug exposure. To explore this further, we evaluated the locomotor responses to repeated cocaine administration in adolescent and adult male DBA/2J mice and alterations in extracellular levels of dopamine (DA) and glutamate (GLU) in the nucleus accumbens (NAc) in response to a subsequent cocaine challenge. Adolescent and adult mice were treated daily with saline or cocaine (10 mg/kg, i.p) for 9 consecutive days. Ten days following the last injection, animals were implanted with microdialysis probes and 24 h later microdialysis samples were collected before and after an acute cocaine challenge. Adolescents but not adults demonstrated development of behavioral sensitization to cocaine. Microdialysis procedures revealed that cocaine-treated mice displayed greater peak increases in extracellular DA in response to a subsequent cocaine challenge as compared to saline-treated mice, in contrast with lower peak increases in extracellular GLU. While adults exhibited greater peaks in extracellular DA in response to cocaine than adolescents did, adolescent mice presented a more rapid onset of peak extracellular DA levels than adults. Our results indicate differences in the behavioral and neurochemical responses to cocaine in adolescent versus adult mice, which may be relevant to the increased risk of developing addiction in humans who are exposed to drugs of abuse during adolescence. (C) 2007 Elsevier B.V. All rights reserved.

VIABILITY OF SPORULATED OOCYSTS OF NEOSPORA CANINUM AFTER EXPOSURE TO DIFFERENT PHYSICAL AND CHEMICAL TREATMENTS

The aim of the present study was to evaluate the viability of Neospora caninum sporulated oocysts after various chemical and physical treatments. Bioassays in gerbils and molecular techniques (PCR-RFLP) were used for identification of the oocysts shed by experimentally infected dogs. Sporulated oocysts were purified and divided into 11 treatment groups as follows: absolute ethanol for 1 hr; 20 C for 6 hr; 4 C for 6 hr; 60 C for 1 min; 100 C for 1 min; 10% formaldehyde for 1 hr; 10% ammonia for 1 hr; 2% iodine for 1 hr; 10% sodium hypochlorite for I hr; 70% ethanol for I hr; and one group was left untreated and kept as a positive control. All chemical treatments were performed at room temperature (37 C). A total of 33 gerbils, or 3 gerbils per treatment, were used for bioassays. After treatment, the oocysts were divided into aliquots of 1,000 oocysts and orally administered to gerbils. After 63 days, the gerbils were anesthetized and killed with 0.2 ml of T61; blood and tissue samples were collected for serological (IFAT and western blotting), molecular (real-time PCR), histopathology, and immunohistochemical tests. Treatments were considered effective only if all 5 detection techniques tested negative. High temperatures at 100 C for 1 min and 10% sodium hypochlorite for 1 hr were the only treatments that met this condition, effectively inactivating all oocysts.

Increased expression of fructan 1-exohydrolase in rhizophores of Vernonia herbacea during sprouting and exposure to low temperature

Rhizophores of Vernonia herbacea, an Asteraceae found in the Brazilian Cerrado, store high amounts of fructans that vary in composition over the phenological cycle. Fructan 1-exohydrolase (1-FEH) activity is detectable during the sprouting phase, mainly in the proximal regions of rhizophores, of plants induced to sprout by defoliation and/or cold storage. We found an increase in 1-FEH gene expression during natural and induced sprouting and further enhancement through low-temperature treatment. Furthermore, a comparative analysis of 1-FEH gene expression in different regions of the rhizophores during the transition from dormancy to sprouting is presented. Transcripts were detected mainly in the proximal region, coinciding with high 1-FEH activity and a high concentration of free fructose. Low temperature promoted the accumulation of fructans of a low degree of polymerization (DP) and enhanced 1-FEH activity and gene expression. It is hypothesized that a set of 1-FEH proteins acts in two different ways during fructan mobilization: (1) by hydrolyzing fructo-oligosaccharides and -polysaccharides in sprouting plants (naturally or induced) for carbon supply and (2) by hydrolyzing preferably fructo-polysaccharides under low temperature to maintain the oligosaccharide pool for plant cold acclimation. (C) 2010 Elsevier GmbH. All rights reserved.

Pre and post-natal exposure to ambient level of air pollution impairs memory of rats: the role of oxidative stress

The aims of this study were to evaluate whether air pollution during pre-natal and post-natal phases change habituation and short-term discriminative memories and if oxidants are involved in this process. As secondary objectives, it was to evaluate if the change of filtered to nonfiltered environment could protect the cortex of rats against oxidative stress as well as to modify the behavior of these animals. Wistar, male rats were divided into four groups (n = 12/group): pre and post-natal exposure until adulthood to filtered air (FA); pre-natal period to nonfiltered air (NFA-FA); until (21st post-natal day) and post-natal to filtered air until adulthood (PND21); prenatal to filtered air until PND21 and post-natal to nonfiltered air until adulthood (FA-NFA); pre and post-natal to nonfiltered air (NFA). After 150 days of air pollution exposure, animals were tested in the spontaneous object recognition test to evaluate short-term discriminative and habituation memories. Rats were euthanized; blood was collected for metal determination; cortex dissected for oxidative stress evaluation. There was a significant increase in malondialdehyde (MDA) levels in the NFA group when compared to other groups (FA: 1.730 +/- 0.217; NFA-FA: 1.101 +/- 0.217; FA-NFA: 1.014 +/- 0.300; NFA: 5.978 +/- 1.920 nmol MDA/mg total proteins; p = 0.007). NFA group presented a significant decrease in short-term discriminative (FA: 0.603 +/- 0.106; NFA-FA: 0.669 +/- 0.0666; FA-NFA: 0.374 +/- 0.178; NFA: -0.00631 +/- 0.106 sec; p = 0.006) and an improvement in habituation memories when compared to other groups. Therefore, exposure to air pollution during both those periods impairs short-term discriminative memory and cortical oxidative stress may mediate this process.