Gender-related pathways for behavior problems in the offspring of alcoholic fathers

The objective of the present study was to examine gender differences in the influence of paternal alcoholism on children's social-emotional development and to determine whether paternal alcoholism is associated with a greater number of externalizing symptoms in the male offspring. From the Mannheim Study of Risk Children, an ongoing longitudinal study of a high-risk population, the developmental data of 219 children [193 (95 boys and 98 girls) of non-alcoholic fathers, non-COAs, and 26 (14 boys, 12 girls) of alcoholic fathers, COAs] were analyzed from birth to the age of 11 years. Paternal alcoholism was defined according to the ICD-10 categories of alcohol dependence and harmful use. Socio-demographic data, cognitive development, number and severity of behavior problems, and gender-related differences in the rates of externalizing and internalizing symptoms were assessed using standardized instruments (IQ tests, Child Behavior Checklist questionnaire and diagnostic interviews). The general linear model analysis revealed a significant overall effect of paternal alcoholism on the number of child psychiatric problems (F = 21.872, d.f. = 1.217, P < 0.001). Beginning at age 2, significantly higher numbers of externalizing symptoms were observed among COAs. In female COAs, a pattern similar to that of the male COAs emerged, with the predominance of delinquent and aggressive behavior. Unlike male COAs, females showed an increase of internalizing symptoms up to age 11 years. Of these, somatic complaints revealed the strongest discriminating effect in 11-year-old females. Children of alcoholic fathers are at high risk for psychopathology. Gender-related differences seem to exist and may contribute to different phenotypes during development from early childhood to adolescence.

Role of the cardiac nerve in the effect of a novel innocuous stimulus on the heart rate of Megalobulimus mogianensis

The effects of a brief jet of water delivered to the anterior portion of body-head on the heart rate of Megalobulimus mogianensis were determined in a group of intact snails (N = 8), previously prepared for electrocardiogram recording. The heart rate was significantly increased following stimulation. Nevertheless, with repetition of the stimulus there was a significant decrease in the magnitude of the heart rate variation and in the time for the basal heart rate to recover (first stimulus, 7.4 ± 1.2 bpm and 15.5 ± 1.8 min; second stimulus, 4.8 ± 1.0 bpm and 10.6 ± 1.5 min; third stimulus, 5.0 ± 0.3 bpm and 11.1 ± 1.8 min), indicating that this behavioral response undergoes early habituation. To determine the role of the cardiac nerve in mediating the heart rate alterations induced by the jet of water two other groups were tested: denervated animals (N = 8) and sham-operated control animals (N = 8). Although the innocuous stimulus caused the heart rate to increase significantly in both experimental groups, the mean increase in heart rate in denervated animals (3.2 ± 0.4 bpm) was 41% of the value obtained in sham-operated animals (7.8 ± 1.5 bpm), indicating that the cardiac nerve is responsible for 59% of the cardioacceleration induced by the innocuous stimulus. The increase in heart rate observed in denervated animals may be due to an increase in venous return promoted by the intense muscular activity associated with the retraction-protraction of the anterior part of the body induced by the jet of water.

Anabolic steroid- and exercise-induced cardiac stress protein (HSP72) in the rat

The present study investigated the effects of exercise and anabolic-androgenic steroids on cardiac HSP72 expression. Male Wistar rats were divided into experimental groups: nandrolone exercise (NE, N = 6), control exercise (CE, N = 6), nandrolone sedentary (NS, N = 6), and control sedentary (CS, N = 6). Animals in the NE and NS groups received a weekly intramuscular injection (6.5 mg/kg of body weight) of nandrolone decanoate, while those in the CS and CE groups received mineral oil as vehicle. Animals in the NE and CE groups were submitted to a progressive running program on a treadmill, for 8 weeks. Fragments of the left ventricle were collected at sacrifice and the relative immunoblot contents of HSP72 were determined. Heart weight to body weight ratio was higher in exercised than in sedentary animals (P < 0.05, 4.65 ± 0.38 vs 4.20 ± 0.47 mg/g, respectively), independently of nandrolone, and in nandrolone-treated than untreated animals (P < 0.05, 4.68 ± 0.47 vs 4.18 ± 0.32 mg/g, respectively), independently of exercise. Cardiac HSP72 accumulation was higher in exercised than in sedentary animals (P < 0.05, 677.16 ± 129.14 vs 246.24 ± 46.30 relative unit, respectively), independently of nandrolone, but not different between nandrolone-treated and untreated animals (P > 0.05, 560.88 ± 127.53 vs 362.52 ± 95.97 relative unit, respectively) independently of exercise. Exercise-induced HSP72 expression was not affected by nandrolone. These levels of HSP72 expression in response to nandrolone administration suggest either a low intracellular stress or a possible less protection to the myocardium.

Synaptic vesicle pool size, release probability and synaptic depression are sensitive to Ca2+ buffering capacity in the developing rat calyx of Held

The calyx of Held, a specialized synaptic terminal in the medial nucleus of the trapezoid body, undergoes a series of changes during postnatal development that prepares this synapse for reliable high frequency firing. These changes reduce short-term synaptic depression during tetanic stimulation and thereby prevent action potential failures during a stimulus train. We measured presynaptic membrane capacitance changes in calyces from young postnatal day 5-7 (p5-7) or older (p10-12) rat pups to examine the effect of calcium buffer capacity on vesicle pool size and the efficiency of exocytosis. Vesicle pool size was sensitive to the choice and concentration of exogenous Ca2+ buffer, and this sensitivity was much stronger in younger animals. Pool size and exocytosis efficiency in p5-7 calyces were depressed by 0.2 mM EGTA to a greater extent than with 0.05 mM BAPTA, even though BAPTA is a 100-fold faster Ca2+ buffer. However, this was not the case for p10-12 calyces. With 5 mM EGTA, exocytosis efficiency was reduced to a much larger extent in young calyces compared to older calyces. Depression of exocytosis using pairs of 10-ms depolarizations was reduced by 0.2 mM EGTA compared to 0.05 mM BAPTA to a similar extent in both age groups. These results indicate a developmentally regulated heterogeneity in the sensitivity of different vesicle pools to Ca2+ buffer capacity. We propose that, during development, a population of vesicles that are tightly coupled to Ca2+ channels expands at the expense of vesicles more distant from Ca2+ channels.

GABA in the central amygdaloid nucleus modulates the electrolyte excretion and hormonal responses to blood volume expansion in rats

We investigated the involvement of GABAergic mechanisms of the central amygdaloid nucleus (CeA) in unanesthetized rats subjected to acute isotonic or hypertonic blood volume expansion (BVE). Male Wistar rats bearing cannulas unilaterally implanted in the CeA were treated with vehicle, muscimol (0.2 nmol/0.2 µL) or bicuculline (1.6 nmol/0.2 µL) in the CeA, followed by isotonic or hypertonic BVE (0.15 or 0.3 M NaCl, 2 mL/100 g body weight over 1 min). The vehicle-treated group showed an increase in sodium excretion, urinary volume, plasma oxytocin (OT), and atrial natriuretic peptide (ANP) levels compared to control rats. Muscimol reduced the effects of BVE on sodium excretion (isotonic: 2.4 ± 0.3 vs vehicle: 4.8 ± 0.2 and hypertonic: 4.0 ± 0.7 vs vehicle: 8.7 ± 0.6 µEq·100 g-1·40 min-1); urinary volume after hypertonic BVE (83.8 ± 10 vs vehicle: 255.6 ± 16.5 µL·100 g-1·40 min-1); plasma OT levels (isotonic: 15.3 ± 0.6 vs vehicle: 19.3 ± 1 and hypertonic: 26.5 ± 2.6 vs vehicle: 48 ± 3 pg/mL), and ANP levels (isotonic: 97 ± 12.8 vs vehicle: 258.3 ± 28.1 and hypertonic: 160 ± 14.6 vs vehicle: 318 ± 16.3 pg/mL). Bicuculline reduced the effects of isotonic or hypertonic BVE on urinary volume and ANP levels compared to vehicle-treated rats. However, bicuculline enhanced the effects of hypertonic BVE on plasma OT levels. These data suggest that CeA GABAergic mechanisms are involved in the control of ANP and OT secretion, as well as in sodium and water excretion in response to isotonic or hypertonic blood volume expansion.

Protein-energy malnutrition halts hemopoietic progenitor cells in the G0/G1 cell cycle stage, thereby altering cell production rates

Protein energy malnutrition (PEM) is a syndrome that often results in immunodeficiency coupled with pancytopenia. Hemopoietic tissue requires a high nutrient supply and the proliferation, differentiation and maturation of cells occur in a constant and balanced manner, sensitive to the demands of specific cell lineages and dependent on the stem cell population. In the present study, we evaluated the effect of PEM on some aspects of hemopoiesis, analyzing the cell cycle of bone marrow cells and the percentage of progenitor cells in the bone marrow. Two-month-old male Swiss mice (N = 7-9 per group) were submitted to PEM with a low-protein diet (4%) or were fed a control diet (20% protein) ad libitum. When the experimental group had lost about 20% of their original body weight after 14 days, we collected blood and bone marrow cells to determine the percentage of progenitor cells and the number of cells in each phase of the cell cycle. Animals of both groups were stimulated with 5-fluorouracil. Blood analysis, bone marrow cell composition and cell cycle evaluation was performed after 10 days. Malnourished animals presented anemia, reticulocytopenia and leukopenia. Their bone marrow was hypocellular and depleted of progenitor cells. Malnourished animals also presented more cells than normal in phases G0 and G1 of the cell cycle. Thus, we conclude that PEM leads to the depletion of progenitor hemopoietic populations and changes in cellular development. We suggest that these changes are some of the primary causes of pancytopenia in cases of PEM.

Immune cells and oxidative stress in the endotoxin tolerance mouse model

Sepsis is a systemic inflammatory response that can lead to tissue damage and death. In order to increase our understanding of sepsis, experimental models are needed that produce relevant immune and inflammatory responses during a septic event. We describe a lipopolysaccharide tolerance mouse model to characterize the cellular and molecular alterations of immune cells during sepsis. The model presents a typical lipopolysaccharide tolerance pattern in which tolerance is related to decreased production and secretion of cytokines after a subsequent exposure to a lethal dose of lipopolysaccharide. The initial lipopolysaccharide exposure also altered the expression patterns of cytokines and was followed by an 8- and a 1.5-fold increase in the T helper 1 and 2 cell subpopulations. Behavioral data indicate a decrease in spontaneous activity and an increase in body temperature following exposure to lipopolysaccharide. In contrast, tolerant animals maintained production of reactive oxygen species and nitric oxide when terminally challenged by cecal ligation and puncture (CLP). Survival study after CLP showed protection in tolerant compared to naive animals. Spleen mass increased in tolerant animals followed by increases of B lymphocytes and subpopulation Th1 cells. An increase in the number of stem cells was found in spleen and bone marrow. We also showed that administration of spleen or bone marrow cells from tolerant to naive animals transfers the acquired resistance status. In conclusion, lipopolysaccharide tolerance is a natural reprogramming of the immune system that increases the number of immune cells, particularly T helper 1 cells, and does not reduce oxidative stress.

Long-term melatonin treatment reduces ovarian mass and enhances tissue antioxidant defenses during ovulation in the rat

Melatonin regulates the reproductive cycle, energy metabolism and may also act as a potential antioxidant indoleamine. The present study was undertaken to investigate whether long-term melatonin treatment can induce reproductive alterations and if it can protect ovarian tissue against lipid peroxidation during ovulation. Twenty-four adult female Wistar rats, 60 days old (± 250-260 g), were randomly divided into two equal groups. The control group received 0.3 mL 0.9% NaCl + 0.04 mL 95% ethanol as vehicle, and the melatonin-treated group received vehicle + melatonin (100 µg·100 g body weight-1·day-1) both intraperitoneally daily for 60 days. All animals were killed by decapitation during the morning estrus at 4:00 am. Body weight gain and body mass index were reduced by melatonin after 10 days of treatment (P < 0.05). Also, a marked loss of appetite was observed with a fall in food intake, energy intake (melatonin 51.41 ± 1.28 vs control 57.35 ± 1.34 kcal/day) and glucose levels (melatonin 80.3 ± 4.49 vs control 103.5 ± 5.47 mg/dL) towards the end of treatment. Melatonin itself and changes in energy balance promoted reductions in ovarian mass (20.2%) and estrous cycle remained extensive (26.7%), arresting at diestrus. Regarding the oxidative profile, lipid hydroperoxide levels decreased after melatonin treatment (6.9%) and total antioxidant substances were enhanced within the ovaries (23.9%). Additionally, melatonin increased superoxide dismutase (21.3%), catalase (23.6%) and glutathione-reductase (14.8%) activities and the reducing power (10.2% GSH/GSSG ratio). We suggest that melatonin alters ovarian mass and estrous cyclicity and protects the ovaries by increasing superoxide dismutase, catalase and glutathione-reductase activities.

Leptin and adiponectin in the female life course

Adipose tissue secretes a variety of adipokines, including leptin and adiponectin, which are involved in endocrine processes regulating glucose and fatty metabolism, energy expenditure, inflammatory response, immunity, cardiovascular function, and reproduction. The present article describes the fluctuations in circulating leptin and adiponectin as well as their patterns of secretion in women from birth to menopause. During pregnancy, leptin and adiponectin seem to act in an autocrine/paracrine fashion in the placenta and adipose tissue, playing a role in the maternal-fetal interface and contributing to glucose metabolism and fetal development. In newborns, adiponectin levels are two to three times higher than in adults. Full-term newborns have significantly higher leptin and adiponectin levels than preterms, whereas small-for-gestational-age infants have lower levels of these adipokines than adequate-for-gestational-age newborns. However, with weight gain, leptin concentrations increase significantly. Children between 5 and 8 years of age experience an increase in leptin and a decrease in adiponectin regardless of body mass index, with a reversal of the newborn pattern for adiponectin: plasma adiponectin levels at age five are inversely correlated with percentage of body fat. In puberty, leptin plays a role in the regulation of menstrual cycles. In adults, it has been suggested that obese individuals exhibit both leptin resistance and decreased serum adiponectin levels. In conclusion, a progressive increase in adiposity throughout life seems to influence the relationship between leptin and adiponectin in women.

Mapping and signaling of neural pathways involved in the regulation of hydromineral homeostasis

Several forebrain and brainstem neurochemical circuitries interact with peripheral neural and humoral signals to collaboratively maintain both the volume and osmolality of extracellular fluids. Although much progress has been made over the past decades in the understanding of complex mechanisms underlying neuroendocrine control of hydromineral homeostasis, several issues still remain to be clarified. The use of techniques such as molecular biology, neuronal tracing, electrophysiology, immunohistochemistry, and microinfusions has significantly improved our ability to identify neuronal phenotypes and their signals, including those related to neuron-glia interactions. Accordingly, neurons have been shown to produce and release a large number of chemical mediators (neurotransmitters, neurohormones and neuromodulators) into the interstitial space, which include not only classic neurotransmitters, such as acetylcholine, amines (noradrenaline, serotonin) and amino acids (glutamate, GABA), but also gaseous (nitric oxide, carbon monoxide and hydrogen sulfide) and lipid-derived (endocannabinoids) mediators. This efferent response, initiated within the neuronal environment, recruits several peripheral effectors, such as hormones (glucocorticoids, angiotensin II, estrogen), which in turn modulate central nervous system responsiveness to systemic challenges. Therefore, in this review, we shall evaluate in an integrated manner the physiological control of body fluid homeostasis from the molecular aspects to the systemic and integrated responses.

Changes in expression of BDNF and its receptors TrkB and p75NTR in the hippocampus of a dog model of chronic alcoholism and abstinence

Chronic ethanol consumption can produce learning and memory deficits. Brain-derived neurotrophic factor (BDNF) and its receptors affect the pathogenesis of alcoholism. In this study, we examined the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) in the hippocampus of a dog model of chronic alcoholism and abstinence. Twenty domestic dogs (9-10 months old, 15-20 kg; 10 males and 10 females) were obtained from Harbin Medical University. A stable alcoholism model was established through ad libitum feeding, and anti-alcohol drug treatment (Zhong Yao Jie Jiu Ling, the main ingredient was the stems of watermelon; developed in our laboratory), at low- and high-doses, was carried out. The Zhong Yao Jie Jiu Ling was effective for the alcoholism in dogs. The morphology of hippocampal neurons was evaluated using hematoxylin-eosin staining. The number and morphological features of BDNF, TrkB and p75NTR-positive neurons in the dentate gyrus (DG), and the CA1, CA3 and CA4 regions of the hippocampus were observed using immunohistochemistry. One-way ANOVA was used to determine differences in BDNF, TrkB and p75NTR expression. BDNF, TrkB and p75NTR-positive cells were mainly localized in the granular cell layer of the DG and in the pyramidal cell layer of the CA1, CA3 and CA4 regions (DG>CA1>CA3>CA4). Expression levels of both BDNF and TrkB were decreased in chronic alcoholism, and increased after abstinence. The CA4 region appeared to show the greatest differences. Changes in p75NTR expression were the opposite of those of BDNF and TrkB, with the greatest differences observed in the DG and CA4 regions.

Relationship between salt consumption measured by 24-h urine collection and blood pressure in the adult population of Vitória (Brazil)

High salt intake is related to an increase in blood pressure and development of hypertension. However, currently, there are no national representative data in Brazil using the gold standard method of 24-h urine collection to measure sodium consumption. This study aimed to determine salt intake based on 24-h urine collection in a sample of 272 adults of both genders and to correlate it with blood pressure levels. We used a rigorous protocol to assure an empty bladder prior to initiating urine collection. We excluded subjects with a urine volume <500 mL, collection period outside of an interval of 23-25 h, and subjects with creatinine excretion that was not within the range of 14.4-33.6 mg/kg (men) and 10.8-25.2 mg/kg (women). The mean salt intake was 10.4±4.1 g/day (d), and 94% of the participants (98% of men and 90% of women) ingested more than the recommended level of 5 g/d. We found a positive association between salt and body mass index (BMI) categories, as well as with salt and blood pressure, independent of age and BMI. The difference in systolic blood pressure reached 13 mmHg between subjects consuming less than 6 g/d of salt and those ingesting more than 18 g/d. Subjects with hypertension had a higher estimated salt intake than normotensive subjects (11.4±5.0 vs 9.8±3.6 g/d, P<0.01), regardless of whether they were under treatment. Our data indicate the need for interventions to reduce sodium intake, as well the need for ongoing, appropriate monitoring of salt consumption in the general population.

The effect of a diet education with six iso-caloric meals on the body weight and blood glucose of diabetes type 2 patients

The treatment of Diabetes should not only be sought through drug administration; diet is also a part of its treatment. The aim of this study was to determine the effect of a diet with six meals having equal calories on the body weight and blood glucose on diabetes type 2 patients. This research is an Experimental study conducted in 2009 on 181 patients with diabetes. The patients visited the IDSF (Iranian Diabetes Society of Fars) weekly and the patients to be studied were randomly divided into two groups of 85 and 96 patients, respectively. The participants were repeatedly requested to consume their calculated calorie in six equal parts. The average age in the Experimental and Control groups were 51.2 ± 13.3 and 53.1 ± 9.4, respectively. The mean body weight and fasting blood glucose at the beginning of the study in Experimental and Control groups were 66.3 ± 9.4 and 69.1 ± 11.1 kg, 198.9 ± 35.1, and 199.8 ± 39.1 mg.dL-1, respectively. At the end of the study, however, the values were 63.5 ± 7.5 and 66.98 ± 9 kg, 139.5 ± 34.6 and 164.2 ± 22.1 mg.dL-1, respectively. Only the mean fasting blood glucose at the end of the study revealed a significant difference (p-value = 0.001). The results show that educating those afflicted with Diabetes Type 2 aiming at changing their diet can greatly help them manage their blood glucose.

From inference to affordance : the problem of visual depth-perception in the optical writings of Descartes, Berkeley, and Gibson

This thesis explores the debate and issues regarding the status of visual ;,iferellces in the optical writings of Rene Descartes, George Berkeley and James 1. Gibson. It gathers arguments from across their works and synthesizes an account of visual depthperception that accurately reflects the larger, metaphysical implications of their philosophical theories. Chapters 1 and 2 address the Cartesian and Berkelean theories of depth-perception, respectively. For Descartes and Berkeley the debate can be put in the following way: How is it possible that we experience objects as appearing outside of us, at various distances, if objects appear inside of us, in the representations of the individual's mind? Thus, the Descartes-Berkeley component of the debate takes place exclusively within a representationalist setting. Representational theories of depthperception are rooted in the scientific discovery that objects project a merely twodimensional patchwork of forms on the retina. I call this the "flat image" problem. This poses the problem of depth in terms of a difference between two- and three-dimensional orders (i.e., a gap to be bridged by one inferential procedure or another). Chapter 3 addresses Gibson's ecological response to the debate. Gibson argues that the perceiver cannot be flattened out into a passive, two-dimensional sensory surface. Perception is possible precisely because the body and the environment already have depth. Accordingly, the problem cannot be reduced to a gap between two- and threedimensional givens, a gap crossed with a projective geometry. The crucial difference is not one of a dimensional degree. Chapter 3 explores this theme and attempts to excavate the empirical and philosophical suppositions that lead Descartes and Berkeley to their respective theories of indirect perception. Gibson argues that the notion of visual inference, which is necessary to substantiate representational theories of indirect perception, is highly problematic. To elucidate this point, the thesis steps into the representationalist tradition, in order to show that problems that arise within it demand a tum toward Gibson's information-based doctrine of ecological specificity (which is to say, the theory of direct perception). Chapter 3 concludes with a careful examination of Gibsonian affordallces as the sole objects of direct perceptual experience. The final section provides an account of affordances that locates the moving, perceiving body at the heart of the experience of depth; an experience which emerges in the dynamical structures that cross the body and the world.

Level and precision of behavioural thermoregulation in the bearded dragon, Pogona vitticeps : effects of hypoxia and environmental thermal quality /

Most metabolic functions are optimized within a narrow range of body temperatures, which is why thermoregulation is of great importance for the survival and overall fitness of an animal. It has been proposed that lizards will thermoregulate less precisely in low thermal quality environments, where the costs associated with thermoregulation are high; in the case of lizards, whose thermoregulation is mainly behavioural, the primary costs ofthermoregulation are those derived from locomotion. Decreasing thermoregulatory precision in costly situations is a strategy that enhances fitness by allowing lizards to be more flexible to changing environmental conditions. It allows animals to maximize the benefits of maintaining a relatively high body temperature while minimizing energy expenditure. In situations where oxygen concentration is low, the costs of thermoregulation are relatively high (i.e. in relation to the amount of oxygen available for metabolic functions). As a result, it is likely that exposures to hypoxic conditions induce a decrease in the precision of thermoregulation. This study evaluated the effects of hypoxia and low environmental thermal quality, two energetically costly conditions, on the precision and level of thermoregulation in the bearded dragon, Pogona vitticeps, in an electronic temperature-choice shuttle box. Four levels of hypoxia (1O, 7, 5 and 4% 02) were tested. Environmental thermal quality was manipulated by varying the rate of temperature change (oTa) in an electronic temperature-choice shuttle box. Higher oT a's translate into more thermally challenging environments, since under these conditions the animals are forced to move a greater number of times (and hence invest more energy in locomotion) to maintain similar temperatures than at lower oTa's. In addition, lizards were tested in an "extreme temperatures" treatment during which air temperatures of the hot and cold compartments of the shuttle box were maintained at a constant 50 and 15°C respectively. This was considered the most thermally challenging environment. The selected ambient (T a) and internal body temperatures (Tb) of bearded dragons, as well as the thermoregulatory precision (measured by the central 68% ofthe Ta and T b distribution) were evaluated. The thermoregulatory response was similar to both conditions. A significant increase in the size of the Tb range, reflecting a decrease in thermoregulatory precision, and a drop in preferred body temperature of ~2 °C, were observed at both 4% oxygen and at the environment of lowest thermal quality. The present study suggests that in energetically costly situations, such as the ones tested in this study, the bearded dragon reduces energy expenditure by decreasing preferred body temperature and minimizing locomotion, at the expense of precise behavioural thermoregulation. The close similarity of the behavioural thermoregulatory response to two very different stimuli suggests a possible common mechanism and neuronal pathway to the thermoregulatory response.