Autoimmunity does not contribute to the highly prevalent glucose metabolism disturbances in a Japanese Brazilian population

The Japanese Brazilian population has one of the highest prevalences of diabetes worldwide. Despite being non-obese according to standard definitions, their body fat distribution is typically central. We investigated whether a subset of these subjects had autoantibodies that would suggest a slowly progressive form of type 1 diabetes. A total of 721 Japanese Brazilians (386 men) in the 30- to 60-year age group underwent clinical examination and laboratory procedures, including a 75-g oral glucose tolerance test and determinations of serum autoantibodies. Antibodies to glutamic acid decarboxylase (GADab) were determined by radioimmunoassay and to thyroglobulin (TGab) and thyroperoxidase (TPOab) by flow-cytometry assays. Mean body mass index was 25.2 ± 3.8 kg/m2, but waist circumference was elevated according to the Asian standards. Diabetes, impaired glucose tolerance, and impaired fasting glycemia were found in 31%, 22%, and 22%, respectively, and 53% of the subjects had metabolic syndrome. Glutamic acid decarboxylase (GADab) was positive in 4.72%, TGab in 9.6%, and TPOab in 10% of the whole sample. When participants were stratified according to the presence of thyroid antibodies, similar frequencies of GADab were found in positive and negative groups. The prevalence rates of glucose metabolism disturbances did not differ between GADab positive and negative groups. Our data did not support the view that autoimmune injury could contribute to the high prevalence of diabetes seen in Japanese Brazilians, and the presence of co-morbidities included in the spectrum of metabolic syndrome favors the classification as type 2 diabetes.

Eimeria stiedai: Metabolism of lipids, proteins and glucose in experimentally infected rabbits, Oryctolagus cuniculus

Rabbits were experimentally infected with sporulated Eimeria stiedai oocysts. A total of 50 white adult rabbits, New Zealand race, were distributed into two groups: Group A was infected with 1x10 4 sporulated Eimeria stiedai oocysts, while group B was inoculated with distilled water as a control. The animals generally displayed increased levels of total protein, globulin, total cholesterol, LDL-c and triacylglycerols; however, total levels of liver lipids and HDL-c decreased, and plasma glucose levels varied during the experimental period. In sum, Eimeria stiedai infection of rabbits caused a considerable number of changes in the metabolism of lipids, proteins and glucose, which is likely due to direct effects of liver cirrhosis on normal body function.

Advances in sickle cell disease treatment: From drug discovery until the patient monitoring

Sickle Cell Disease (SCD) is one of the most prevalent hematological diseases in the world. Despite the immense progress in molecular knowledge about SCD in last years few therapeutical sources are currently available. Nowadays the treatment is performed mainly with drugs such as hydroxyurea or other fetal hemoglobin inducers and chelating agents. This review summarizes current knowledge about the treatment and the advancements in drug design in order to discover more effective and safe drugs. Patient monitoring methods in SCD are also discussed. © 2011 Bentham Science Publishers Ltd.

Salmonella enterica serovar typhimurium colonizing the lumen of the chicken intestine grows slowly and upregulates a unique set of virulence and metabolism genes

The pattern of global gene expression in Salmonella enterica serovar Typhimurium bacteria harvested from the chicken intestinal lumen (cecum) was compared with that of a late-log-phase LB broth culture using a whole-genome microarray. Levels of transcription, translation, and cell division in vivo were lower than those in vitro. S. Typhimurium appeared to be using carbon sources, such as propionate, 1,2-propanediol, and ethanolamine, in addition to melibiose and ascorbate, the latter possibly transformed to D-xylulose. Amino acid starvation appeared to be a factor during colonization. Bacteria in the lumen were non- or weakly motile and nonchemotactic but showed upregulation of a number of fimbrial and Salmonella pathogenicity island 3 (SPI-3) and 5 genes, suggesting a close physical association with the host during colonization. S. Typhimurium bacteria harvested from the cecal mucosa showed an expression profile similar to that of bacteria from the intestinal lumen, except that levels of transcription, translation, and cell division were higher and glucose may also have been used as a carbon source. © 2011, American Society for Microbiology.

Effects of hydric deficiency on gas exchange parameters and metabolism of Eucalyptus grandis clones

The metabolic effects caused by hydric deficiency (HD) on Eucalyptus grandis clones were assessed by an experiment where plants were cultivated in four blocks. The first was the control block, normally irrigated, whereas the other three blocks were submitted to cycles of hydric deficiency. Analysis of photosynthetic efficiency, enzymatic activity of antioxidant response system, level of pigments and L-proline concentration were performed to evaluate the HD effects. Results showed that HD altered some parameters related to photosynthetic activity, pigments accumulation, proline and enzymatic activity. Clone 433 of E. grandis presented higher response ability to HD.

β-conglycinin combined with fenofibrate or rosuvastatin have exerted distinct hypocholesterolemic effects in rats

Background: There is increasing interest in non-pharmacological control of cholesterol and triglyceride levels in the plasma and diet-drug association represent an important area of studies. The objective of this study was to observe the hypocholesterolemic effect of soybean β-conglycinin (7S protein) alone and combined with fenofibrate and rosuvastatin, two hypolipidemic drugs. Methods. The protein and drugs were administered orally once a day to rats and the effects were evaluated after 28 days. Wistar rats were divided into six groups (n = 9): hypercholesterolemic diet (HC), HC+7S protein (300 mg.kg-1 day-1) (HC-7S), HC+fenofibrate (30 mg.kg-1 day-1)(HC-FF), HC+rosuvastatin (10 mg.kg-1 day-1)(HC-RO), HC+7S+fenofibrate (HC-7S-FF) and HC+7S+rosuvastatin (HC-7S-RO). Results: Animals in HC-7S, HC-FF and HC-RO exhibited reductions of 22.9, 35.8 and 18.8% in total plasma cholesterol, respectively. In HC-7S-FF, animals did not show significant alteration of the level in HC+FF while the group HC-7S-RO showed a negative effect in comparison with groups taking only protein (HC-7S) or drug (HC-RO). The administration of the protein, fenofibrate and rosuvastatin alone caused increases in the plasma HDL-C of the animals, while the protein-drug combinations led to an increase compared to HC-FF and HC-RO. The plasma concentration of triacylgycerides was significantly reduced in the groups without association, while HC-7S-FF showed no alteration and HC-7S-RO a little reduction. Conclusion: The results of our study indicate that conglycinin has effects comparable to fenofibrate and rosuvastatin on the control of plasma cholesterol, HDL-C and triacylglycerides, when given to hypercholesterolemic rats, and suggests that the association of this protein with rosuvastatin alters the action of drug in the homeostasis of cholesterol. © 2012 Ferreira et al; licensee BioMed Central Ltd.

Effect of percutaneous transthoracic lung biopsy on oxidative metabolism in sheep

This study aimed to assess the effect of percutaneous transthoracic lung biopsy on the oxidative metabolism of sheep by measuring the oxidative stress markers of superoxide dismutase (SOD), total glutathione (GSH-t), peroxidase (GSH-Px) and thiobarbituric acid reactive substances (TBARS) in the red cells of these animals. Blood samples were collected from 20 clinically healthy sheep prior to, and 30 min after, percutaneous transthoracic lung biopsy. After biopsy, there was a significant decrease (p < 0.05) in SOD and GSH-Px activity, with no significant change (p ≥ 0.05) in GSH-t and TBARS concentrations. These results showed that percutaneous transthoracic lung biopsy did not significantly affect the oxidative metabolism of sheep 30 min after the procedure, which may be used widely in this species without causing serious tissue damage. © 2012. The Authors.

Combined effects of age and diet-induced obesity on biochemical parameters and cardiac energy metabolism in rats

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

High concentrations of glucose reduce the oxidative metabolism of dog neutrophils in vitro

Background: Dogs are commonly affected by hyperglycemic conditions. Hyperglycemia compromises the immune response and favors bacterial infections; however, reports on the effects of glucose on neutrophil oxidative metabolism and apoptosis are conflicting in humans and rare in dogs. Considering the many complex factors that affect neutrophil oxidative metabolism in vivo, we investigated in vitro the specific effect of high concentrations of glucose on superoxide production and apoptosis rate in neutrophils from healthy dogs.Results: The capacity of the neutrophils to reduce tetrazolium nitroblue decreased significantly in the higher concentration of glucose (15.13 ± 9.73% (8 mmol/L) versus 8.93 ± 5.71% (16 mmol/L)). However, there were no changes in tetrazolium nitroblue reduction at different glucose concentrations when the neutrophils were first activated with phorbol myristate acetate. High concentrations of glucose did not affect the viability and apoptosis rate of canine neutrophils either with or without prior camptothecin stimulation. This study provides the first evidence that high concentrations of glucose inhibit the oxidative metabolism of canine neutrophils in vitro in a manner similar to that which occurs in humans, and that the decrease in superoxide production did not increase the apoptosis rate.Conclusions: A high concentration of glucose reduces the oxidative metabolism of canine neutrophils in vitro. It is likely that glucose at high concentrations rapidly affects membrane receptors responsible for the activation of NADPH oxidase in neutrophils; therefore, the nonspecific immune response can be compromised in dogs with acute and chronic hyperglycemic conditions. © 2013 Bosco et al.; licensee BioMed Central Ltd.

Canonical WNT signaling regulates development of bovine embryos to the blastocyst stage

Objectives were to evaluate the role of canonical WNT signaling in development of the preimplantation embryo. Signaling was activated with 2-Amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine (AMBMP) and inhibited with Dickkopf-related protein 1 (DKK1). Treatment of bovine embryos with AMBMP at day 5 after insemination decreased development to the blastocyst stage at day 7 and reduced numbers of trophectoderm and inner cell mass cells. At high concentrations, AMBMP caused disorganization of the inner cell mass. DKK1 blocked actions of AMBMP but did not affect development in the absence of AMBMP. Examination of gene expression in day 6 morulae by microarray revealed expression of 16 WNT genes and other genes involved in WNT signaling; differences in relative expression were confirmed by PCR for 7 genes. In conclusion, the preimplantation embryo possesses a functional WNT signaling system and activation of the canonical pathway can inhibit embryonic development.

Silibinin attenuates oxidative metabolism and cytokine production by monocytes from preeclamptic women.

Silibinin is a polyphenolic plant flavonoid with anti-inflammatory properties. The present study investigated the effect of silibinin on oxidative metabolism and cytokine production - tumor necrosis factor-alpha (TNF-α), interleukin (IL)12, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, IL-10, and transforming growth factor beta (TGF-β1) - by peripheral blood monocytes (PBM) from preeclamptic pregnant women. It is a case-controlled study involving women with preeclampsia (PE, n = 30) compared with normotensive pregnant (NT, n = 30) and with non-pregnant (NP, n = 30) women. Monocytes were obtained and cultured with or without silibinin (5 μM or 50 μM) for 18 h. Superoxide anion (O2-) and hydrogen peroxide (H2O2) release were determined by specific assays, and cytokine levels were determined by immunoenzymatic assays (ELISA). Monocytes from preeclamptic women cultured without stimulus released higher levels of O22, H2O2 and TNF-α, and lower levels of IL-10 and TGF-β1 than did monocytes from NT and NP women. Treatment in vitro with silibinin significantly inhibited spontaneous O2- and H2O2 release and TNF-α production by monocytes from preeclamptic women. The main effect of silibinin was obtained at 50 μM concentration. Thus, silibinin exerts anti-oxidative and anti-inflammatory effects on monocytes from preeclamptic pregnant women by inhibiting the in vitro endogenous release of reactive oxygen species and TNF-α production.

Energy Metabolism in Cardiac Remodeling and Heart Failure

Fatty acids are the main substrates used by mitochondria to provide myocardial energy under normal conditions. During heart remodeling, however, the fuel preference switches to glucose. In the earlier stages of cardiac remodeling, changes in energy metabolism are considered crucial to protect the heart from irreversible damage. Furthermore, low fatty acid oxidation and the stimulus for glycolytic pathway lead to lipotoxicity, acidosis, and low adenosine triphosphate production. While myocardial function is directly associated with energy metabolism, the metabolic pathways could be potential targets for therapy in heart failure. © 2013 by Lippincott Williams & Wilkins.

From doubly labelled water to half-life; validating radio-isotopic rubidium turnover to measure metabolism in small vertebrates

The doubly labelled water method (DLW) is widely used to measure field metabolic rate (FMR), but it has some limitations. Here, we validate an innovative technique for measuring FMR by comparing the turnover of isotopic rubidium (86Rb kb) with DLW depletion and the rate of CO2 production (V·co2) measured by flow-through respirometry (FTR) for two dunnart species (Marsupialia: Dasyuridae), Sminthopsis macroura (17 g) and Sminthopsis ooldea (10 g). The rate of metabolism as assessed by V·co2 (FTR) and 86Rb kb was significantly correlated for both species (S. macroura, r2 = 0·81, P = 1·19 × 10-5; S. ooldea, r2 = 0·63, P = 3·84 × 10-4), as was V·co2 from FTR and DLW for S. macroura (r2 = 0·43, P = 0·039), but not for S. ooldea (r2 = 0·29, P = 0·168). There was no relationship between V·co2 from DLW and 86Rb kb for either species (S. macroura r2 = 0·22, P = 0·169; S. ooldea r2 = 0·21, P = 0·253). We conclude that 86Rb kb provided useful estimates of metabolic rate for dunnarts. Meta-analysis provided different linear relationships between V·co2 and 86Rb kb for endotherms and ectotherms, suggesting different proportionalities between metabolic rate and 86Rb kb for different taxa. Understanding the mechanistic basis for this correlation might provide useful insights into the cause of these taxonomic differences in the proportionality. At present, it is essential that the relationship between metabolic rate and 86Rb kb be validated for each taxon of interest. The advantages of the 86Rb technique over DLW include lower equipment requirements and technical expertise, and the longer time span over which measurements can be made. The 86Rb method might be particularly useful for estimating FMR of groups for which the assumptions of the DLW technique are compromised (e.g. amphibians, diving species and fossorial species), and groups that are practically challenging for DLW studies (e.g. insects). © 2013 British Ecological Society.

Lipid metabolism of commercial layers fed diets containing aflatoxin, fumonisin, and a binder

Aflatoxins (AF) and fumonisins (FU) are a major problem faced by poultry farmers, leading to huge economic losses. This experiment was conducted to determine the effects of AF (1 mg/kg of feed) and FU (25 mg/kg of feed), singly or in combination, on the lipid metabolism in commercial layers and investigate the efficacy of a commercial binder (2 kg/t of feed) on reducing the toxic effects of these mycotoxins. A total of 168 Hisex Brown layer hens, 37 wk of age, were randomized into a 3 × 2 + 1 factorial arrangement (3 diets with no binder containing AF, FU, and AF+FU; 3 diets with binder containing AF, FU, and AF+FU; and a control diet with no mycotoxins and binders), totaling 7 treatments. The hens contaminated with AF showed the characteristic effects of aflatoxicosis, such as a yellow liver, resulting from the accumulation of liver fat, lower values of plasma very low-density lipoprotein and triglycerides, and higher relative weight of the kidneys and liver. Hepatotoxic and nephrotoxic effects of FU were not observed in this study. On the other hand, the FU caused a reduction in small intestine length and an increase in abdominal fat deposition. The glucan-based binder prevented some of the deleterious effects of these mycotoxins, particularly the effects of AF on hepatic lipid metabolism, kidney relative weight, and FU in the small intestine. © 2013 Poultry Science Association Inc.

Leishmaniasis causes oxidative stress and alteration of oxidative metabolism and viability of neutrophils in dogs

The aim of the present study was to test the hypothesis that oxidative stress and alteration of oxidative metabolism and apoptosis of neutrophils in dogs vary with the stage of leishmaniasis and to determine the contribution of uremia to such alterations. Dogs with leishmaniasis were classified into two stages: moderate (Leish II, n = 20) or very severe (i.e. with concurrent uremia; Leish IV, n = 20) according to the LeishVet Consensus. The two leishmaniasis groups were compared with uremic dogs without leishmaniasis (Uremic, n = 10) and to healthy dogs (Control, n = 30). To determine oxidative stress, total antioxidant/oxidant capacity, lipid peroxidation, total glutathione and the plasma antioxidants albumin, uric acid and bilirubin were quantified. Superoxide production was determined using the hydroethidine probe and viability and apoptosis were measured using annexin V-PE by capillary flow cytometry. Oxidative stress was present in both uremia and leishmaniasis with reduced total antioxidant capacity and was associated with increased induced production of superoxide and apoptosis. The greatest amount of oxidants was observed in animals with moderate disease only. Neutrophils from uremic dogs with and without leishmaniasis had decreased viability and an increased apoptosis rate in addition to increased lipid peroxidation. In conclusion, oxidative stress occurs in both stages of leishmaniasis with differences in intensity and levels of plasma markers; however, uremia does contribute to the decreased spontaneous viability of neutrophils in dogs in the final stage of the disease. © 2013 Elsevier Ltd. All rights reserved.