Study of Blood Porphyrin Spectral Profile for Diagnosis of Chronic Renal Failure

The progression to end-stage renal failure is independent of the initial pathogenic mechanism. Metabolic acidosis is a common consequence of chronic renal failure that results from inadequate ammonium excretion and decreased tubular bicarbonate reabsorption. Protoporphyrin IX (PpIX) is the immediate metabolic precursor of the heme molecule. The purpose of this study was to evaluate the levels of erythrocytes protoporphyrin IX at an animal model during progressive renal disease. A total of 36 eight-week-old male Wistar rats were divided into six groups: Normal, 4 and 8 weeks after 5/6 nephrectomy (NX). Renal function was evaluated by creatinine clearance and plasma creatinine levels. The autofluorescence of erythrocytes porphyrin of healthy and NX rats was analyzed using fluorescence spectroscopy. Emission spectra were obtained by exciting the samples at 405 nm. Significant differences between normal and NX rats autofluorescence shape occurred in the 600-700 nm spectral region. A correlation was observed between emission band intensity at 635 nm and progression of renal disease.

Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic acidemia

Methylmalonic acidemia is one of the most prevalent inherited metabolic disorders involving neurological deficits. In vitro experiments, animal model studies and tissue analyses from human patients suggest extensive impairment of mitochondrial energy metabolism in this disease. This review summarizes changes in mitochondrial energy metabolism occurring in methylmalonic acidemia, focusing mainly on the effects of accumulated methylmalonic acid, and gives an overview of the results found in different experimental models. Overall, experiments to date suggest that mitochondrial impairment in this disease occurs through a combination of the inhibition of specific enzymes and transporters, limitation in the availability of substrates for mitochondrial metabolic pathways and oxidative damage.

Genetic heterogeneity of within-family variance of body weight in Atlantic salmon (Salmo salar)

BACKGROUND: Canalization is defined as the stability of a genotype against minor variations in both environment and genetics. Genetic variation in degree of canalization causes heterogeneity of within-family variance. The aims of this study are twofold: (1) quantify genetic heterogeneity of (within-family) residual variance in Atlantic salmon and (2) test whether the observed heterogeneity of (within-family) residual variance can be explained by simple scaling effects. RESULTS: Analysis of body weight in Atlantic salmon using a double hierarchical generalized linear model (DHGLM) revealed substantial heterogeneity of within-family variance. The 95% prediction interval for within-family variance ranged from ~0.4 to 1.2 kg2, implying that the within-family variance of the most extreme high families is expected to be approximately three times larger than the extreme low families. For cross-sectional data, DHGLM with an animal mean sub-model resulted in severe bias, while a corresponding sire-dam model was appropriate. Heterogeneity of variance was not sensitive to Box-Cox transformations of phenotypes, which implies that heterogeneity of variance exists beyond what would be expected from simple scaling effects. CONCLUSIONS: Substantial heterogeneity of within-family variance was found for body weight in Atlantic salmon. A tendency towards higher variance with higher means (scaling effects) was observed, but heterogeneity of within-family variance existed beyond what could be explained by simple scaling effects. For cross-sectional data, using the animal mean sub-model in the DHGLM resulted in biased estimates of variance components, which differed substantially both from a standard linear mean animal model and a sire-dam DHGLM model. Although genetic differences in canalization were observed, selection for increased canalization is difficult, because there is limited individual information for the variance sub-model, especially when based on cross-sectional data. Furthermore, potential macro-environmental changes (diet, climatic region, etc.) may make genetic heterogeneity of variance a less stable trait over time and space.

Investigating the Effects of Mifepristone (RU486) in the Behavioral, Hormonal and Central Responses to Acute Stress

Depression is associated with glucocorticoid hypersecretion, due to dysfunction of the hypothalamo-pituitary-adrenocorticol axis (HPA-axis). Because excess glucocorticoids are associated with depressive-like features in humans, glucocorticoid receptor antagonists are currently being tested for antidepressant efficacy in clinical trials. In the current study the hypothesis that mifepristone (RU486), a glucocorticoid receptor antagonist, would decrease the neuroendocrine and central HPA-axis responses to an acute stressor and attentuate depressive like behavior in an animal model of behavioral helplessness (forced swim test) was tested. Adult male rats were treated with 10 mglkg RU486 (subcutaneous) for five days and then exposed to a IO-minute forced swim test (FST), conducted in Plexiglas cylinders. FST sessions were videotaped for later analysis of behavioral immobility. Plasma ACTH and corticosterone CORT were measured at 15min and 90min after FST cessation. Animals were perfused and brains were collected for immunocytochemical assessment of c-Fos expression in the medial prefrontal cortex (mPFC), a brain region implicated in both depression and central control of the HPA axis. RU486 significantly decreased peak ACTH and CORT concentrations following FST exposure. In addition, glucocorticoid negative feedback was at1enuated in RU486-treated animals exposed to the FST. Exposure to FST alone induced c-FOS expression in the mPFC, as measured by the number of c-Fos positive neurons. Treatment with RU486 significantly increased the number of rnPFC c-Fos positive cell following FST exposure. The behavioral data obtained from FST paradigm, demonstrated that RU486 decreased immobility in the FST illustrating the potential efficacy of this drug as an antidepressant. Collectively these data suggest that RU486 dampens HPA-axis responses to stress, possibly by enhancing the excitability of stress-inhibitory neurons in the mPFC. This is particularly exciting, given the fact that this neural region is associated with decreased neural activity during depression in humans.

Influência do modo ventilatório no desempenho funcional dos enxertos pulmonares pós-transplante em modelo canino : ventilção controlada a volume versus ventilação controlada a pressão

O conhecimento dos riscos e conseqüências da lesão pulmonar induzida pela ventilação mecânica mudou a filosofia da terapia respiratória e tem influenciado nas recomendações e padronizações de seu uso. A influência dos diferentes modos ventilatórios não tem sido estudada em transplante de pulmão. O presente estudo teve como objetivo comparar a influência da ventilação controlada a volume (VCV) com a ventilação controlada a pressão (PCV) no desempenho funcional dos enxertos pulmonares, em modelo canino de transplante pulmonar unilateral utilizando-se doadores após três horas de parada cardiocirculatória. Quinze cães foram randomizados em dois grupos: oito cães foram alocados para o Grupo VCV e sete cães para o Grupo PCV. Cinco cães não completaram o período de avaliação pós-transplante, os dez animais restantes, grupo VCV (n= 5) e grupo PCV (n=5), foram avaliados durante 360 min após o término do transplante pulmonar. O desempenho funcional dos enxertos foi estudado através da avaliação da mecânica respiratória, trocas gasosas e das alterações histopatológicas. Não foram encontradas diferenças significativas em nenhuma das variáveis da mecânica respiratória estudadas (pressões de pico inspiratória- PPI; pressões de platô- PPLAT ; pressões médias de vias aéreas – Pmédia; complacências dinâmica- Cdyn e estática- Cst); da oxigenação, pressão parcial de oxigênio no sangue arterial e venoso misto (PaO2, PvO2); a diferença entre a saturação da hemoglobina no sangue arterial e no sangue venoso misto (ΔSO2); a pressão parcial de dióxido de carbono no sangue arterial e no sangue venoso misto (PaCO2, PvO2). As alterações histopatológicas encontradas nos pulmões dos animais foram compatíveis com o padrão de lesão pulmonar aguda. As alterações histológicas de padrão inespecífico não tiveram nenhuma correlação com o modo ventilatório. Este estudo demonstra que os modos ventilatórios estudados não influenciam as respostas dos enxertos pulmonares à lesão de isquemia reperfusão que se estabelece precocemente neste modelo experimental até 6 horas de reperfusão pulmonar pós-transplante unilateral.

Caracterização físico-química e efeitos de frações polissacarídicas da alga amansia multifida na coagulação, inflamação, radicais livres e viabilidade celular

Galactans are polysaccharides sulfated present in the cell wall of red algae. Carrageenans are galactans well known in the food industry as gelling polysaccharides and for induce inflammatory process in rodents as animal model. The extraction of polysaccharides from A. multifida has been carried out by proteolysis and precipitation in different volumes of acetone, which produced three fractions (F1, F2, and FT). Chemical and physical analyses revealed that these fractions are sulfated galactan predominantly. Results of the antioxidant activity assays showed that all of these fractions have antioxidant activity and that was associated with sulfate content of the analysis of reducing power and total antioxidant capacity. However, these fractions were not effective against lipid peroxidation. The fraction FT presented higher activity on the APTT test at 200 μg (> 240 s). The assessment of the hemolytic activity showed that the FT fraction has the best activity, increasing lyses by the complement system to 42.3% (50 μg) (p< 0,001). The fraction FT showed the best yield, anticoagulant and hemolytic activity between the three fractions and therefore it was choose for the in vivo studies. The Inflammation assessment using the FT fraction (50 mg / kg MB) showed that the cellular migration and the IL-6 production increased 670.1% (p< 0,001) and 531.8% (p< 0,001), respectively. These results confirmed its use as an inflammation inducer in animal model. Cytotoxicity assay results showed that all fractions have toxic effects on 3T3 and HeLa cells after exposition of 48 hours, except when 100 μg for both F1 and FT were used. These results arise the discussion whether these polysaccharides it should be used as additive in foods, cosmetics and medicines.

Estudo do papel da proteína multifuncional APE1/Ref-1 sobre a resposta inflamatória na meningite bacteriana

Despite advances in antibiotic therapy, bacterial meningitis (BM) remains with high mortality and morbidity rates in worldwide. One important mechanism associated to sequels during disease is the intense inflammatory response which promotes an oxidative burst and release of reactive oxygen species, consequently leading to cell death. Activation of DNA repair enzymes during oxidative stress has been demonstrated in several neurological disorders. APE1/Ref-1 is a multifunctional protein involved in DNA repair and plays a redox function on transcription factors such as NFkB and AP-1.The aim of this study was assess the role of APE1/Ref-1 on inflammatory response and the possibility of its modulation to reduce the sequels of the disease. Firstly it was performed an assay to measure cytokine in cerebrospinal fluid of patients with BM due to Streptococcus pneumoniae and Neisseriae meningitides. Further, a cellular model of inflammation was used to observe the effect of the inhibition of the endonuclease and redox activity of APE1/Ref-1 on cytokine levels. Additionally, APE1/Ref-1 expression in cortex and hippocampus of rat with MB after vitamin B6 treatment was evaluated. Altogether, results showed a similar profile of cytokines in the cerebrospinal fluid of patients from both pathogens, although IFNy showed higher expression in patients with BM caused by S. pneumoniae. On the other hand, inhibitors of APE1/Ref-1 reduced cytokine levels, mainly TNF-α. Reduction of oxidative stress markers was also observed after introduction of inhibitors in the LPS-stimulated cell. In the animal model, BM increased the expression of the protein APE1/Ref-1, while vitamin B6 promoted reduction. Thereby, this data rise important factors to be considered in pathogenesis of BM, e.g., IFNy can be used as prognostic factor during corticosteroid therapy, APE1/Ref-1 can be an important target to modulate the level of inflammation and VIII oxidative stress, and vitamin B6 seems modulates several proteins related to cell death. So, this study highlights a new understanding on the role of APE1/Ref-1 on the inflammation and the oxidative stress during inflammation condition

Estimates of genetic parameters for visual scores and their correlation with production and reproductive traits in Brahman cattle

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Stomach fullness modulates prey size choice in the frillfin goby, Bathygobius soporator

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influência da laparoscopia e da laparotomia na gasometria, leucometria diferencial e citocinas em modelo de sepse abdominal em ratos

Laparoscopic surgery is associated with reduced surgical trauma, and less acute phase response, as compared with open surgery. Cytokines are important regulators of the biological response to surgical and anesthetic stress. The aim of this study was to determine if CO2 pneumoperitoneum would change cytokine expression, gas parameters and leukocyte count in septic rats. Methods: Wistar rats were randomly assigned to five groups: control (anesthesia only), laparotomy, CO2 pneumoperitoneum, cecum ligation and puncture by laparotomy, and laparoscopic cecum ligation and puncture. After 30 min of the procedures, arterial blood samples were obtained to determine leukocytes subpopulations by hemocytometer. TNFα, IL-1β, IL-6 were determined in intraperitoneal fluid (by ELISA). Gas parameters were measured on arterial blood, intraperitoneal and subperitoneal exsudates. Results: Peritoneal TNFα, IL-1β and IL-6 concentrations were lower in pneumoperitoneum rats than in all other groups (p<0.05). TNFα, IL-1β and IL-6 expression was lower in the laparoscopic than in laparotomic sepsis (p<0.05). Rats from laparoscopic cecum ligation and puncture group developed significant hypercarbic acidosis in blood and subperitoneal fluid when compared to open procedure group. Total white blood cells and lymphocytes were significantly lower in laparoscopic cecum ligation and puncture rats than in the laparotomic (p<0.01). Nevertheless, the laparotomic cecum ligation rats had a significant increase in blood neutrophils and eosinophils when compared with controls (p<0.05). Conclusions: This study demonstrates that the CO2 pneumoperitoneum reduced the inflammatory and immune response in an animal model of peritonitis with respect to intraperitoneal cytokines, white blood cell count and clinical correlates of sepsis. The pneumoperitoneum produced hypercarbic acidosis in septic animals

Avaliação citológica em base líquida de fármacos moduladores estrogênicos

Hormone therapy is an important tool in the treatment of breast cancer and tamoxifen represents one of the most important drugs used in this type of treatment. Recently other drugs based on the inhibition of aromatase had been developed, this enzyme is responsible for the synthesis of estrogenic esteroids from the androgenic ones. The objective of this study would be the development of a quantitative cytological model of murine estral analysis that allowed the characterization of different hormone drugs effect over vaginal epithelium. The technique of monochromatic staining with Evans blue (C.I. 23860) showed to be efficient in the qualitative and quantitative classification of the cycle. It had been observed differences in the cytological standard of animals submitted to the studied drugs; tamoxifen presented a widening of phases of lesser maturation (diestrais), while anastrozole and exemestane increased the duration of the phases of larger maturation (estrais). The data were analysed through a cubical non linear regression (spline) which allowed a better characterization of the drugs, suggesting a proper cytological profile to the antagonism of the estrogen receptor (tamoxifen), aromatase competition (anastrozole) and inhibition of the enzyme (exemestane)

Parâmetros Genéticos para a Produção de Leite, Gordura e Proteína em Bubalinos

The objective of this study was to estimate the genetic parameters affecting milk production (MP), fat (%F) and protein (%P) contents of buffalo milk. Restricted Maximum Likelihood (REML) using MTDFREML program under animal model analyzed a total of 1744 lactations records from 1268 cows. The means were: MP = 1259.47 +/- 523.09 kg, %F = 6.87 +/- 0.88% and %P = 3.91 +/- 0.61%. The estimates of repeatability and heritability coefficients were: MP = 0.38 and 0.24, %F = 0.28 and 0.21 and %P = 0.30 and 0.26, respectively. The estimated genetic and phenotypic correlations were MP x %F = -0.18 and -0.62, MP x %P = -0.23 and -0.59 and %F x %P = 0.50 and 0.77, respectively. According to these results it is possible to conclude that selection is a proper way to increase milk yield, fat and protein percentage. Although negative low values of genetic correlations among traits, it should be take into account that simultaneous selection based on these traits could not be so efficient.

Índices de seleção para um rebanho Caracu de duplo propósito

Neste trabalho, objetivou-se determinar índices de seleção para um rebanho da raça Caracu de duplo propósito, cujo objetivo de seleção (H) incluiu a venda de bezerros desmamados e a produção de leite. As características que compuseram H foram: produção total de leite, idade ao primeiro parto, período de serviço, peso à desmama e duração da vida produtiva. Foram propostos dois índices de seleção para H. Os critérios de seleção adotados no índice 1 foram: produção de leite na primeira lactação, primeiro período de serviço, peso à desmama (PD) e perímetro escrotal. No índice 2, foram consideradas as mesmas características, sendo, entretanto, o ganho médio diário do nascimento à desmama empregado como critério de seleção para PD. As análises estatísticas para a obtenção dos componentes de (co)variâncias e das estimativas dos parâmetros genéticos e fenotípicos foram realizadas pelo método da máxima verossimilhança restrita livre de derivada, por um modelo animal (uni e bi-característica). As informações zootécnicas e genealógicas, os preços e as quantidades dos insumos e dos produtos foram obtidos no escritório da empresa estudada. Os custos de produção e as receitas da atividade pecuária foram determinados para o período de 1994 a 2000. A equação de lucro foi tomada em base anual, usando-se valores médios para número de animais por categoria, características biológicas e preços..¹ O valor econômico para cada característica foi obtido pela derivada parcial da função de lucro em relação à característica em questão. Os dois índices econômicos de seleção trariam considerável resposta para o objetivo proposto. Entretanto, o índice 1, que incluiu PD, seria um pouco mais eficiente em termos de resposta à seleção total.

Genotype-environment interaction for post-weaning traits in Nellore beef cattle

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Genetic associations between age at first calving and heifer body weight and scrotal circumference in Nelore cattle

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)