Alstonine as an Antipsychotic: Effects on Brain Amines and Metabolic Changes

Managing schizophrenia has never been a trivial matter. Furthermore, while classical antipsychotics induce extrapyramidal side effects and hyperprolactinaemia, atypical antipsychotics lead to diabetes, hyperlipidaemia, and weight gain. Moreover, even with newer drugs, a sizable proportion of patients do not show significant improvement. Alstonine is an indole alkaloid identified as the major component of a plant-based remedy used in Nigeria to treat the mentally ill. Alstonine presents a clear antipsychotic profile in rodents, apparently with differential effects in distinct dopaminergic pathways. The aim of this study was to complement the antipsychotic profile of alstonine, verifying its effects on brain amines in mouse frontal cortex and striatum. Additionally, we examined if alstonine induces some hormonal and metabolic changes common to antipsychotics. HPLC data reveal that alstonine increases serotonergic transmission and increases intraneuronal dopamine catabolism. In relation to possible side effects, preliminary data suggest that alstonine does not affect prolactin levels, does not induce gains in body weight, but prevents the expected fasting-induced decrease in glucose levels. Overall, this study reinforces the proposal that alstonine is a potential innovative antipsychotic, and that a comprehensive understanding of its neurochemical basis may open new avenues to developing newer antipsychotic medications.

Inhibition of phospholipase A(2) in rat brain decreases the levels of total Tau protein

The microtubule-associated protein Tau promotes the assembly and stability of microtubules in neuronal cells. Six Tau isoforms are expressed in adult human brain. All six isoforms become abnormally hyperphosphorylated and form neurofibrillary tangles in Alzheimer disease (AD) brains. In AD, reduced activity of phospholipase A(2) (PLA(2)), specifically of calcium-dependent cytosolic PLA(2) (cPLA(2)) and calcium-independent intracellular PLA(2) (iPLA(2)), was reported in the cerebral cortex and hippocampus, which positively correlated with the density of neurofibrillary tangles. We previously demonstrated that treatment of cultured neurons with a dual cPLA(2) and iPLA(2) inhibitor, methyl arachidonyl fluorophosphonate (MAFP), decreased total Tau levels and increased Tau phosphorylation at Ser(214) site. The aim of this study was to conduct a preliminary investigation into the effects of in vivo infusion of MAFP into rat brain on PLA(2) activity and total Tau levels in the postmortem frontal cortex and dorsal hippocampus. PLA(2) activity was measured by radioenzymatic assay and Tau levels were determined by Western blotting using the anti-Tau 6 isoforms antibody. MAFP significantly inhibited PLA(2) activity in the frontal cortex and hippocampus. The reactivity to the antibody revealed three Tau protein bands with apparent molecular weight of close to 40, 43 and 46 kDa in both brain areas. MAFP decreased the 46 kDa band intensity in the frontal cortex, and the 43 and 46 kDa band intensities in the hippocampus. The results indicate that in vivo PLA(2) inhibition in rat brain decreases the levels of total (nonphosphorylated plus phosphorylated) Tau protein and corroborate our previous in vitro findings.

Leptin Targets in the Mouse Brain

The central actions of leptin are essential for homeostatic control of adipose tissue mass, glucose metabolism, and many autonomic and neuroendocrine systems. In the brain, leptin acts on numerous different cell types via the long-form leptin receptor (LepRb) to elicit its effects. The precise identification of leptin`s cellular targets is fundamental to understanding the mechanism of its pleiotropic central actions. We have systematically characterized LepRb distribution in the mouse brain using in situ hybridization in wildtype mice as well as by EYFP immunoreactivity in a novel LepRb-IRES-Cre EYFP reporter mouse line showing high levels of LepRb mRNA/EYFP coexpression. We found substantial LepRb mRNA and EYFP expression in hypothalamic and extrahypothalamic sites described before, including the dorsomedial nucleus of the hypothalamus, ventral premammillary nucleus, ventral tegmental area, parabrachial nucleus, and the dorsal vagal complex. Expression in insular cortex, lateral septal nucleus, medial preoptic area, rostral linear nucleus, and in the Edinger-Westphal nucleus was also observed and had been previously unreported. The LepRb-IRES-Cre reporter line was used to chemically characterize a population of leptin receptor-expressing neurons in the midbrain. Tyrosine hydroxylase and Cre reporter were found to be coexpressed in the ventral tegmental area and in other midbrain dopaminergic neurons. Lastly, the LepRbI-RES-Cre reporter line was used to map the extent of peripheral leptin sensing by central nervous system (CNS) LepRb neurons. Thus, we provide data supporting the use of the LepRb-IRES-Cre line for the assessment of the anatomic and functional characteristics of neurons expressing leptin receptor. J. Comp. Neurol. 514:518-532, 2009. (C) 2009 Wiley-Liss, Inc.

Effect of different cleansers on the weight and ion release of removable partial denture: an in vitro study

OBJECTIVE: Removable partial dentures (RPD) require different hygiene care, and association of brushing and chemical cleansing is the most recommended to control biofilm formation. However, the effect of cleansers has not been evaluated in RPD metallic components. The aim of this study was to evaluate in vitro the effect of different denture cleansers on the weight and ion release of RPD. MATERIAL AND METHODS: Five specimens (12x3 mm metallic disc positioned in a 38x18x4 mm mould filled with resin), 7 cleanser agents [Periogard (PE), Cepacol (CE), Corega Tabs (CT), Medical Interporous (MI), Polident (PO), 0.05% sodium hypochlorite (NaOCl), and distilled water (DW) (control)] and 2 cobalt-chromium alloys [DeguDent (DD), and VeraPDI (VPDI)] were used for each experimental situation. One hundred and eighty immersions were performed and the weight was analyzed with a high precision analytic balance. Data were recorded before and after the immersions. The ion release was analyzed using mass spectrometry with inductively coupled plasma. Data were analyzed by two-way ANOVA and Tukey HSD post hoc test at 5% significance level. RESULTS: Statistical analysis showed that CT and MI had higher values of weight loss with higher change in VPDI alloy compared to DD. The solutions that caused more ion release were NaOCl and MI. CONCLUSIONS: It may be concluded that 0.05% NaOCl and Medical Interporous tablets are not suitable as auxiliary chemical solutions for RPD care.

Production and body composition traits of broilers in relation to breast weight evaluated by path analysis

Breast weight has great economic importance in poultry industry, and may be associated with other variables. This work aimed to estimate phenotypic correlations between performance (live body weight at 7 and 28 days, and at slaughter, and depth of the breast muscle measured by ultrasonography), carcass (eviscerated body weight and leg weight) and body composition (heart, liver and abdominal fat weight) traits in a broiler line, and quantify the direct and indirect influence of these traits on breast weight. Path analysis was used by expanding the matrix of partial correlation in coefficients which give the direct influence of one trait on another, regardless the effect of the other traits. The simultaneous maintenance of live body weight at slaughter and eviscerated body weight in the matrix of correlations might be harmful for statistical analysis involving systems of normal equations, like path analysis, due to the observed multicollinearity. The live body weight at slaughter and the depth of the breast muscle as measured by ultrasonography directly affected breast weight and were identified as the most responsible factors for the magnitude of the correlation coefficients obtained between the studied traits and breast weight. Individual pre-selection for these traits could favor an increased breast weight in the future reproducer candidates of this line if the broilers' environmental conditions and housing are maintained, since the live body weight at slaughter and the depth of breast muscle measured by ultrasonography were directly related to breast weight.

Categorization skills and recall in brain damaged children: a multiple case study

During development, children become capable of categorically associating stimuli and of using these relationships for memory recall. Brain damage in childhood can interfere with this development. This study investigated categorical association of stimuli and recall in four children with brain damages. The etiology, topography and timing of the lesions were diverse. Tasks included naming and immediate recall of 30 perceptually and semantically related figures, free sorting, delayed recall, and cued recall of the same material. Traditional neuropsychological tests were also employed. Two children with brain damage sustained in middle childhood relied on perceptual rather than on categorical associations in making associations between figures and showed deficits in delayed or cued recall, in contrast to those with perinatal lesions. One child exhibited normal performance in recall despite categorical association deficits. The present results suggest that brain damaged children show deficits in categorization and recall that are not usually identified in traditional neuropsychological tests.

Weight of evidence

Evidence-based Medicine (EBM) has become a major source of medical knowledge. It handles complexities of virtually every method or technique used in research. The knowledge on how the EBM researcher retrieves information, judges for relevance and analyzes derived data is invaluable for the skillful reader of medical scientific reports.

Experimental nodel of C6 brain tumors in athymic rats

Malignant brain tumor experimental models tend to employ cells that are immunologically compatible with the receptor animal. In this study, we have proposed an experimental model of encephalic tumor development by injecting C6 cells into athymic Rowett rats, aiming at reaching a model which more closely resembles to the human glioma tumor. In our model, we observed micro-infiltration of tumor cell clusters in the vicinity of the main tumor mass, and of more distal isolated tumor cells immersed in normal encephalic parenchyma. This degree of infiltration is superior to that usually observed in other C6 models.

Synthesis and structural characterization of block and random low molecular weight copolymers composed of L-lactic acid and isosorbide succinate moieties

Isosorbide succinate moieties were incorporated into poly(L-lactide) (PLLA) backbone in order to obtain a new class of biodegradable polymer with enhanced properties. This paper describes the synthesis and characterization of four types of low molecular weight copolymers. Copolymer I was obtained from monomer mixtures of L-lactide, isosorbide, and succinic anhydride; II from oligo(L-lactide) (PLLA), isosorbide, and succinic anhydride; III from oligo(isosorbide succinate) (PIS) and L-lactide; and IV from transesterification reactions between PLLA and PIS. MALDI-TOFMS and 13C-NMR analyses gave evidence that co-oligomerization was successfully attained in all cases. The data suggested that the product I is a random co-oligomer and the products II-IV are block co-oligomers.

O desmame precoce afeta o ganho de peso e a composição corporal em camundongos adultos?

OBJETIVO: Avaliar o efeito do desmame precoce sobre o ganho de peso e a composição corporal de camundongos adultos jovens. MÉTODOS: Camundongos Swiss Webster, machos, foram desmamados precocemente (14º dia de vida) ou amamentados até o 21º dia de vida (grupo controle). Após o desmame, os animais foram alimentados com ração elaborada para roedores em crescimento até o 63º dia de vida, quando então foram sacrificados. RESULTADOS: O peso corporal dos animais do grupo desmamado de forma precoce foi significantemente maior no 28º, 35º e no 63º dias de vida em relação ao grupo controle (p<0,05). Porém, o consumo de ração não diferiu entre os grupos. A concentração sérica de proteínas totais, albumina e ferro, bem como a concentração hepática, muscular e cerebral de proteínas, ácido desoxirribonucléico e a relação proteína/ácido ribonucléico, não diferiram significantemente entre os grupos. O grupo desmamado precocemente apresentou maior quantidade absoluta de massa magra, lipídeos, proteínas e cinzas, em comparação ao grupo controle (p<0,05). A quantidade relativa de umidade, lipídeos, massa magra, proteínas e cinzas não diferiu entre os grupos. CONCLUSÃO: O desmame precoce, associado à ingestão de ração elaborada para roedores em crescimento, resultou em aumento do ganho de peso, porém não afetou a composição corporal de camundongos adultos.

Validity and reliability of self-reported weight and height measures for the diagnoses of adolescent's nutritional status

OBJETIVO: Avaliar a validade do peso, estatura e Índice de Massa Corporal (IMC) referidos e sua confiabilidade para o diagnóstico do estado nutricional de adolescentes de Piracicaba. MÉTODOS: Participaram do estudo 360 adolescentes de ambos os sexos, de escolas públicas de Piracicaba, com idade entre 10 e 15 anos. Os adolescentes auto-relataram seu peso e estatura, sendo esses valores obtidos por medidas diretas, logo em seguida, pelos entrevistadores. A validade do IMC referido foi calculada segundo índices de sensibilidade, especificidade e valor preditivo positivo (VPP). Avaliou-se a concordância entre as categorias de IMC obtido por meio das medidas referidas e aferidas a partir do coeficiente kappa ponderado, coeficiente de correlação de Lin. e gráficos de Bland e Altman e Lin. RESULTADOS: Verificou-se que tanto os meninos quanto as meninas subestimaram o peso (-1,0 meninas e meninos) e a estatura (meninas -1,2 e meninos -0,8) (p < 0,001). Os valores de IMC aferidos e referidos apresentaram uma concordância moderada. A sensibilidade do IMC referido para classificar os indivíduos obesos foi maior para os meninos (87,5%), enquanto a especificidade foi maior para as meninas (92,7%). O VPP foi elevado somente para a classificação da eutrofia. CONCLUSÕES: As medidas referidas de peso e estatura de adolescentes não representam medidas válidas e, portanto, não devem ser usadas em substituição aos valores mensurados. Além disso, verificou-se que 10% dos meninos obesos e 40% das meninas obesas poderiam permanecer não identificados utilizando-se as medidas auto-referidas, confirmando a baixa validade das medidas auto-referidas.

Ratio of weight to height gain: a useful tool for identifying children at risk of becoming overweight or obese at preschool age

PURPOSE: To analyze the usefulness of the weight gain/height gain ratio from birth to two and three years of age as a predictive risk indicator of excess weight at preschool age. METHODS: The weight and height/length of 409 preschool children at daycare centers were measured according to internationally recommended rules. The weight values and body mass indices of the children were transformed into a z-score per the standard method described by the World Health Organization. The Pearson correlation coefficients (rP) and the linear regressions between the anthropometric parameters and the body mass index z-scores of preschool children were statistically analyzed (alpha = 0.05). RESULTS: The mean age of the study population was 3.2 years (± 0.3 years). The prevalence of excess weight was 28.8%, and the prevalence of overweight and obesity was 8.8%. The correlation coefficients between the body mass index z-scores of the preschool children and the birth weights or body mass indices at birth were low (0.09 and 0.10, respectively). There was a high correlation coefficient (rP = 0.79) between the mean monthly gain of weight and the body mass index z-score of preschool children. A higher coefficient (rP = 0.93) was observed between the ratio of the mean weight gain per height gain (g/cm) and the preschool children body mass index z-score. The coefficients and their differences were statistically significant. CONCLUSION: Regardless of weight or length at birth, the mean ratio between the weight gain per g/cm of height growth from birth presented a strong correlation with the body mass index of preschool children. These results suggest that this ratio may be a good indicator of the risk of excess weight and obesity in preschool-aged children.

Recovery and upgrading bovine rumen protein by extrusion: effect of lipid content on protein disulphide cross-linking, solubility and molecular weight

Bovine rumen protein with two levels of residual lipids (1.9 per cent or 3.8 per cent) was subjected to thermoplastic extrusion under different temperatures and moisture contents. Protein solubility in different buffers, disulphide cross-linking and molecular weight distribution were determined on the extrudates. After extrusion, samples with 1.9 per cent residual lipids content had a higher concentration of protein insoluble by undetermined forces, irrespective of feed moisture and processing temperature used. Lipid content of 3.8 per cent in the feed material resulted in more protein participating in the extrudate network through non-covalent interactions (hydrophobic and electrostatic) and disulphide bonds. A small dependency of the extrusion process on moisture and temperature and a marked dependency on lipid content, especially phospholipid, was observed, Electrophoresis under non-reducing conditions showed that protein extrusion with low feed moisture promoted high molecular breakdown inside the barrel, probably due to intense shear force, and further protein aggregation at the die end

The relationship between birth weight and insulin resistance in childhood

Chronic diseases that are typical of adulthood may originate in intra-uterine life through inadequate fetal development. The present epidemiological cohort study of 506 healthy children aged 5\20138 years evaluated the relationship between birth weight and insulin resistance in an age group that has been assessed in few similar studies. Insulin concentration was determined by chemiluminescence and insulin resistance by the homeostasis model assessment (HOMA). Blood glucose, total cholesterol and fractions (LDL cholesterol and HDL cholesterol) and TAG concentrations were determined by automated enzymatic methods. Linear regression analysis investigated the relationship between birth weight (assessed as a continuous variable and in three categories: small for gestational age, SGA; adequate for gestational age and large for gestational age) and the HOMA index, using backward stepwise selection and biological models to explain the causal pathway of the relationship. There were negativeassociations between birth weight (P < 0·001), SGA (P = 0·027) and the HOMA index, and a positive association between waist circumference (P < 0·001) and the HOMA index. Considering the significant associations between birth weight and waist circumference (P < 0·001) and waist circumference and insulin resistance (P < 0·001), we can probably suspect that lower birth weight is a common cause of higher waist circumference and insulin resistance. In summary, the results of the present study showed increased insulin resistance in apparently healthy, young children, who had lower weight at birth and higher measurements of waist circumference. There is a need to develop public health policies that adopt preventive measures to promote adequate maternal-fetal and child development and enable early diagnosis of metabolic abnormalities

The Brain as a Distributed Intelligent Processing System: An EEG Study

Background: Various neuroimaging studies, both structural and functional, have provided support for the proposal that a distributed brain network is likely to be the neural basis of intelligence. The theory of Distributed Intelligent Processing Systems (DIPS), first developed in the field of Artificial Intelligence, was proposed to adequately model distributed neural intelligent processing. In addition, the neural efficiency hypothesis suggests that individuals with higher intelligence display more focused cortical activation during cognitive performance, resulting in lower total brain activation when compared with individuals who have lower intelligence. This may be understood as a property of the DIPS. Methodology and Principal Findings: In our study, a new EEG brain mapping technique, based on the neural efficiency hypothesis and the notion of the brain as a Distributed Intelligence Processing System, was used to investigate the correlations between IQ evaluated with WAIS (Whechsler Adult Intelligence Scale) and WISC (Wechsler Intelligence Scale for Children), and the brain activity associated with visual and verbal processing, in order to test the validity of a distributed neural basis for intelligence. Conclusion: The present results support these claims and the neural efficiency hypothesis.