Glucokinase Regulatory Protein genetic variant interacts with omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome

Glucokinase Regulatory Protein (GCKR) plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been of considerable interest, due to their potential to reduce metabolic syndrome (MetS) risk. Objective To examine whether genetic variability at the GCKR gene locus was associated with the degree of insulin resistance, plasma concentrations of C-reactive protein (CRP) and n-3 PUFA in MetS subjects. Design Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-B, plasma concentrations of C-peptide, CRP, fatty acid composition and the GCKR rs1260326-P446L polymorphism, were determined in a cross-sectional analysis of 379 subjects with MetS participating in the LIPGENE dietary cohort. Results Among subjects with n-3 PUFA levels below the population median, carriers of the common C/C genotype had higher plasma concentrations of fasting insulin (P = 0.019), C-peptide (P = 0.004), HOMA-IR (P = 0.008) and CRP (P = 0.032) as compared with subjects carrying the minor T-allele (Leu446). In contrast, homozygous C/C carriers with n-3 PUFA levels above the median showed lower plasma concentrations of fasting insulin, peptide C, HOMA-IR and CRP, as compared with individuals with the T-allele. Conclusions We have demonstrated a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in MetS subjects. Further studies are needed to confirm this gene-diet interaction in the general population and whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals.

Dyslipidaemia and insulin resistance in vertically HIV-infected children and adolescents

This cross-sectional study determined the influence of antiretroviral therapy (ART) on the lipid profile and insulin sensitivity of 119 perinatally HIV-infected Brazilian patients aged 6-19 years. Inadequate high-density lipoprotein cholesterol (HDL-c) concentrations were observed in 81.4% of patients. High concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDI.-c) and triglycerides (TG) were found in 33.9%, 9.7% and 35.6% of patients, respectively. There were statistically significant differences in mean concentrations of TC (P=0.004), HDL-c (P=0.015) and LDL-c (P=0.028) among children (< 10 years), early adolescents (10-14 years) and late adolescents (15-19 years). Children presented the highest mean concentrations of TC and LDL-c, and patients in late adolescence presented the lowest concentrations of HDL-c. Insulin sensitivity, assessed by the Homeostasis Model Assessment (HOMA) index, was diagnosed in 16.7% of patients, with a statistically higher proportion (P=0.034) of insulin-resistant children (33.3%) compared with adolescents (12.5%). There was a statistically significant association between TG concentrations and use of ART regimens containing protease inhibitors (PI) (P=0.0003). Children presented a higher prevalence of insulin resistance and dyslipidaemia compared with adolescents, suggesting that ART, especially Pls, may lead to metabolic complications. (C) 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Calcium intake and its relationship with adiposity and insulin resistance in post-pubertal adolescents

Background Dietary calcium intake has been described as being a negative contributor to adiposity. In adolescents, this relationship is not well established. The objectives of the present study were to compare the calcium intake of normal-weight and obese adolescents and to evaluate its relationship with adiposity and insulin resistance. Methods A cross-sectional analysis of 96 post-pubertal adolescents; 47 normal weight and 49 obese, mean age 16.6 (SD +/- 1.3) years. Body composition was assessed by dual-energy X-ray absorptiometry. Dietary intake was evaluated using a 3-day dietary record. The biochemical evaluation comprised the measurements of serum lipids, lipoproteins, glucose and insulin. Insulin resistance was calculated using the Homeostasis Model Assessment of Insulin resistance (HOMA-IR). Results The mean calcium intake, adjusted for energy, was lower in obese adolescents, 585.2 (+/- 249.9) mg, than in normal weight adolescents, 692.1 (+/- 199.5) mg. Only 4% of adolescents had an adequate intake of calcium. Calcium intake was inversely associated with body trunk fat, insulin and HOMA-IR in the obese group. The quartile analysis of calcium intake provided evidence that girls in the highest quartile had decreased adiposity and insulin resistance. Conclusions This study showed a negative relationship between calcium intake and body fat and insulin resistance, mainly in obese girls, and demonstrates the importance of an increased dietary calcium intake.

Cathepsin S as a biomarker of low-grade inflammation, insulin resistance, and cardiometabolic disease risk

Cathepsin S is a protease important in major histocompatibility complex (MHC) class II antigen presentation and also in degrading the extracellular matrix. Studies, most of them experimental, have shown that cathepsin S is involved in different pathological conditions such as obesity, inflammation, atherosclerosis, diabetes, and cancer.    The overall hypothesis of this report is that high levels of circulating cathepsin S, is a biomarker that reflects pathology induced by inflammation and obesity. The overall aim of this report was to investigate possible associations between circulating cathepsin S, inflammation, glucometabolic disturbance, and its associated diseases in the community. As cathepsin S appears to be a novel risk marker for several pathological conditions, we also wanted to examine the effect of dietary intervention on circulating cathepsin S concentrations.    This thesis is based on data from three community-based cohorts, the Uppsala longitudinal study of adult men (ULSAM), the prospective investigation of the vasculature in Uppsala seniors (PIVUS), and a post-hoc study from the randomized controlled NORDIET trial.    In the first study, we identified a cross-sectional positive association between serum cathepsin S and two markers of cytokine-mediated inflammation, CRP and IL-6. These associations were similar in non-obese individuals. In longitudinal analyses, higher cathepsin S at baseline was associated with higher CRP and IL-6 levels after six years of follow-up. In the second study, we identified a cross-sectional association between increased serum levels of cathepsin S and reduced insulin sensitivity. These associations were similar in non-obese individuals. No significant association was observed between cathepsin S and insulin secretion. In longitudinal analysis, higher cathepsin S levels were associated with an increased risk of developing diabetes during the six-year follow-up. In the third study, we found that higher serum levels of cathepsin S were associated with increased mortality risk. Moreover, in the ULSAM cohort, serum cathepsin S was independently associated with cause-specific mortality from cardiovascular disease and cancer. In the fourth study, we identified that adherence to an ad libitum healthy Nordic diet for 6 weeks slightly decreased the levels of plasma cathepsin S in normal or marginally overweight individuals, relative to the control group. Changes in circulating cathepsin S concentrations were correlated with changes in body weight, LDL-C, and total cholesterol.    Conclusion: This thesis shows that circulating cathepsin S is a biomarker that independently reflects inflammation, insulin resistance, the risk of developing diabetes, and mortality risk. Furthermore, a Nordic diet moderately reduced cathepsin S levels in normal-weight and overweight men and women. This effect may be partially mediated by diet-induced weight loss and possibly by reduced LDL-C concentrations. 

Preparation and characterization of free films of high amylose/pectin mixtures cross-linked with sodium trimetaphosphate

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Dexmedetomidine Alters the Cardiovascular Response During Infra-Renal Aortic Cross-Clamping in Sevoflurane-Anesthetized Dogs

Some properties of the volatile anesthetics, such as vasodilatation and myocardial depression, combined with the sympathetic inhibition that alpha 2-agonists can produce may determine hemodynamic alterations during aortic, surgery. The interaction between dexmedetomidine (DEX), an alpha 2-agonist, and sevoflurane during aortic surgery is unknown. We studied the effects of DEX on hemodynamics and systemic oxygenation during aortic cross-clamping (Aox) and unclamping (UAox) in sevoflurane-anesthetized dogs Twenty dogs were. anesthetized with sevoflurane and were randomly assigned to two groups prior to Aox and UAox: control, n = 10, received saline infusion only, and DEX (1 mu g.kg(-1) load followed by 1 mu g.kg(-1).h(-1) infusion), n = 10. Hemodynamic and oxygenation variables were measured at baseline, after saline or DEX loading dose, 20 and 40 min after Aox, and 20 and 40 min after UAox. After DEX administration, heart rate, cardiac index l and systemic oxygen transport index (131021) were lower than in control group. Aox increased mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) in both groups, but the effects were greater with DEX. Cl, heart rate, and DO(2)I were lower, while central venous pressure (CVP) and pulmonary artery occlusion pressure were higher in DEX compared to control. After UAox, MAP, CVP and SVRI were maintained higher in DEX in relation to control. We conclude that in sevoflurane-anesthetized dogs DEX alters the cardiovascular response during aortic surgery.

Fracture resistance of bleached teeth restored with different procedures

This study evaluated the fracture resistance of teeth submitted to internal bleaching and restored with different non-metallic post. Eighty mandibular incisors were endodontically treated and randomly divided in 10 groups (n = 8): G1- restored with composite resin (CR), G2- CR + fiber-reinforced composite post (FRC, Everstick post, Sticktech) cemented with resin cement self-etch adhesive (RCS, Panavia F 2.0, Kuraray), G3- CR + FRC + self-adhesive resin cement (SRC, Breeze, Pentral Clinical), G4- CR+ glass fiber post (GF, Exacto Post, Angelus) + RCS, G5- CR + GF + SRC. The G6 to G10 were bleached with hydrogen peroxide (HP) and restored with the same restorative procedures used for G1 to G5, respectively. After 7 days storage in artificial saliva, the specimens were submitted to the compressive strength test (N) at 0.5 mm/min cross-head speed and the failure pattern was identified as either reparable (failure showed until 2 mm below the cement-enamel junction) or irreparable (the failure showed <2 mm or more below the cement-enamel). Data were analyzed by ANOVA and Tukey test (α = 0.05). No significant difference (p < 0.05) was found among G1 to G10. The results suggest that intracoronal bleaching did not significantly weaken the teeth and the failure patterns were predominately reparable for all groups. The non-metallic posts in these teeth did not improve fracture resistance.

High-Intensity Resistance Training with Insufficient Recovery Time Between Bouts Induce Atrophy and Alterations in Myosin Heavy Chain Content in Rat Skeletal Muscle

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cross-reactivity between antigens from Amblyomma cajennense and A-hebraeum (Acari : Ixodidae)

Laboratory animals exposed to feeding ticks develop resistance which is reflected by a decline in tick engorgement weight, egg-laying by adults and reduced egg viability. Serum antibodies from these hosts and their reaction with tick antigens have been detected by different methods, including precipitation techniques, immunofluorescent techniques, ELISA and Western blots. However, little is known about the effects of antibodies on ticks that engorge on resistant hosts, or which tissues of the tick body are possibly immunogenic. Some researchers, using immunohistochemistry, have detected host antibodies in the gut, salivary glands and haemolymph of ticks engorged on resistant animals. The same technique has helped considerably in determining antigenic sites or antibody targets in other arthropods. Consequently, immunohistochemistry techniques were used in this study to detect cross-reactivity between sera raised against Amblyomma cajennense (Fabricius, 1787) with Amblyomma hebraeum (Koch, 1844), and vice versa. The results show the existence of shared antigens between the 2 tick species. In general, our results point more to a 1-way cross-reactivity of A. hebraeum with A. cajennense than a reciprocal cross-reactivity, suggesting that A. hebraeum is more immunogenic than A. cajennense.

Development of SCAR marker linked to stem canker resistance gene in soybean

Stem canker caused by the fungus Diaporthe phaseolorum f. sp. meridionalis is a disease that limits soybean cultivation. Phenotypic evaluations aiming at disease resistance require labor-intensive processes, as for instance handling and transport of phytopathogens. The use of DNA markers in the selective procedures eases certain phases, besides being practical, safe and reliable. A RAPD fragment of 588pb was identified among bulks of resistant and susceptible plants in the cross BR92-15454 (R) x IAC-11 (S). Through co-segregation, the distance between the resistance locus and the fragment was estimated at 7.4 ± 2.1 cM, with a Lodmax. of 23.072 (first year) and at 6.0 ± 3.4 cM with a Lodmax. of 7.806 (second year). The fragment was converted into a SCAR marker and digested with enzyme Hinc II, which made the classification in homozygous resistant, heterozygous resistant and susceptible plants possible. This SCAR marker is suitable for use in the improvement program conducted in Jaboticabal.

Myogenin, MyoD and IGF-I regulate muscle mass but not fiber-type conversion during resistance training in rats

The purpose of this study was to test the hypothesis that skeletal muscle adaptations induced by long-term resistance training (RT) are associated with increased myogenic regulatory factors (MRF) and insulin-like growth factor-I (IGF-I) mRNA expression in rats skeletal muscle. Male Wistar rats were divided into 4 groups: 8-week control (C8), 8-week trained (T8), 12-week control (C12) and 12-week trained (T12). Trained rats were submitted to a progressive RT program (4 sets of 10-12 repetitions at 65-75% of the 1RM, 3 day/week), using a squat-training apparatus with electric stimulation. Muscle hypertrophy was determined by measurement of muscle fiber cross-sectional area (CSA) of the muscle fibers, and myogenin, MyoD and IGF-I mRNA expression were measured by RT-qPCR. A hypertrophic stabilization occurred between 8 and 12 weeks of RT (control-relative % area increase, T8: 29% vs. T12: 35%; p>0.05) and was accompanied by the stabilization of myogenin (control-relative % increase, T8: 44.8% vs. T12: 37.7%, p>0.05) and MyoD (control-relative % increase, T8: 22.9% vs. T12: 22.3%, p>0.05) mRNA expression and the return of IGF-I mRNA levels to the baseline (control-relative % increase, T8: 30.1% vs. T12: 1.5%, p<0.05). Moreover, there were significant positive correlations between the muscle fiber CSA and mRNA expression for MyoD (r=0.85, p=0.0001), myogenin (r=0.87, p=0.0001), and IGF-I (r=0.88, p=0.0001). The significant (p<0.05) increase in myogenin, MyoD and IGF-I mRNA expression after 8 weeks was not associated with changes in the fiber-type frequency. In addition, there was a type IIX/D-to-IIA fiber conversion at 12 weeks, even with the stabilization of MyoD and myogenin expression and the return of IGF-I levels to baseline. These results indicate a possible interaction between MRFs and IGF-I in the control of muscle hypertrophy during long-term RT and suggest that these factors are involved more in the regulation of muscle mass than in fiber-type conversion. © Georg Thieme Verlag KG Stuttgart · New York.

Resistance of beef cattle of two genetic groups to ectoparasites and gastrointestinal nematodes in the state of São Paulo, Brazil

The resistance to infestations by ectoparasites and infections by gastrointestinal nematodes was studied in 45 animals (males and females) of two genetic groups: purebred Nelore (NI, n=28) and Three-Cross (1/2 Angus+1/4 Canchim+1/4 Nelore - TC, n=17). The animals were monitored for 24months, during which they were left to graze in tropical pastures without receiving treatment for parasites. Each month the animals were examined for infestations by external parasites, to count the numbers of cattle ticks Rhipicephalus microplus with diameter greater than 4.5mm present on the left side, horn flies (Haematobia irritans) present in the lumbar region and botfly larvae (Dermatobia hominis) present on the entire body. The H. irritans counts were performed with the aid of digital photographs. At the time of examination, fecal samples were collected to count the eggs per gram (EPG) and to perform coprocultures, and peripheral blood samples were drawn to determine the packed cell volume (PCV) and to count the eosinophils. For statistical analysis, the count data were transformed into log10 (n+1), where n is the number of parasites. For PCV, significant effects (P<0.05) were found for collection month (CO), genetic group (GG) and gender (SX), with means and respective standard errors of 41.5±0.65% for the NI animals, 39.3±0.83% for the TC, 41.5±0.72% for the females and 39.3±0.77% for the males. Regarding the eosinophil counts, only the effect of sex was significant (P<0.01), with means and respective standard errors of 926.0±46.2/μL, for males and 1088.0±43.8/μL of blood, for females. The NI animals presented lower mean counts for all the external parasites compared to the TC animals (P<0.01). For ticks, the transformed means followed by standard errors for the NI and TC animals were 0.06±0.01 and 0.34±0.02, while for horn flies these were 0.92±0.05 and 1.36±0.06 and for botfly larvae they were 0.05±0.03 and 0.45±0.05, respectively. The average EPG values were only influenced by CO (P<0.01). The coprocultures revealed the presence of the following endoparasites: Haemonchus spp., Cooperia spp., Oesophagostomum spp. and Trichostrongylus spp., the last in smaller proportion. There were no significant differences between the genetic groups for the endoparasite loads, except for Cooperia spp., which were present in greater number (P<0.05) in the NI group. The results obtained in this experiment confirm previous findings of greater susceptibility of the Nelore breed to Cooperia spp. and high resistance to ectoparasites. © 2013 Elsevier B.V.

Resistance training with excessive training load and insufficient recovery alters skeletal muscle mass-related protein expression

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

Fracture resistance of teeth submitted to several internal bleaching protocols

Aim: The aim of this study was to evaluate the fracture resistance of teeth submitted to several internal bleaching protocols using 35% hydrogen peroxide (35HP), 37% carbamide peroxide (37CP), 15% hydrogen peroxide with titanium dioxide nanoparticles (15HPTiO2) photoactivated by LED-laser or sodium perborate (SP). Materials and methods: After endodontic treatment, fifty bovine extracted teeth were divided into five groups (n = 10): G1-unbleached; G2-35HP; G3-37CP; G4-15HPTiO2 photoactivated by LED-laser and G5-SP. In the G2 and G4, the bleaching protocol was applied in 4 sessions, with 7 days intervals between each session. In the G3 and G5, the materials were kept in the pulp teeth for 21 days, but replaced every 7 days. After 21 days, the teeth were subjected to compressive load at a cross head speed of 0.5 mm/min, applied at 135° to the long axis of the root using an eletromechanical testing machine, until teeth fracture. The data were submitted to ANOVA and Tukey tests (α = 5%). Results: The 35HP, 37CP, 15HPTiO2 and SP showed similar fracture resistance teeth reduction (p > 0.05). All bleaching treatments reduced the fracture resistance compared to unbleached teeth (p < 0.05). Conclusion: All bleaching protocols reduced the fracture resistance of endodontically-treated teeth, but there were no differences between each other. Clinical significance: There are several internal bleaching protocols using hydrogen peroxide in different concentrations and activation methods. This study evaluated its effects on fracture resistance in endodontically-treated teeth.

Fracture resistance of endodontically-treated teeth submitted to bleaching treatment with hydrogen peroxide and titanium dioxide nanoparticles photoactivated by LED-laser

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)