Models to predict nitrogen excretion from beef cattle fed a wide range of diets compiled from South America.

The objective of this meta-analysis was to develop and evaluate models for predicting nitrogen (N) excretion in feces, urine, and manure in beef cattle in South America. The study incorporated a total of 1,116 individual observations of N excretion in feces and 939 individual observations of N excretion in feces and in urine (g/d), representing a diverse range of diets, animal genotypes, and management conditions in South America. The dataset also included data on dry matter intake (DMI; kg/d) and nitrogen intake (NI; g/d), concentrations of dietary components, as well as average daily gain (ADG; g/d) and average body weight (BW; kg). Models were derived using linear mixed-effects regression with a random intercept for the study. Fecal N excretion was positively associated with DMI, NI, nonfibrous carbohydrates, average BW, and ADG and negatively associated with EE and CP concentration in the diet. The univariate model predicting fecal N excretion based on DMI (model 1) performed slightly better than the univariate model, which used NI as a predictor variable (model 2) with a root mean square error (RMSE) of 38.0 vs. 39.2%, the RMSE-observations SD ratio (RSR) of 0.81 vs. 0.84, and concordance correlation coefficient (CCC) of 0.53 vs. 0.50, respectively. Models predicting urinary N excretion were less accurate than those derived to predict fecal N excretion, with an average RMSE of 43.7% vs. 37.0%, respectively. Urinary and manure N excretion were positively associated with DMI, NI, CP, average BW, and ADG and negatively associated with neutral detergent fiber concentration in the diet. As opposed to fecal N excretion, the univariate model predicting urinary N excretion using NI (model 10) performed slightly better than the univariate model using DMI (model 9) as predictor variable with an RMSE of 36.0% vs. 39.7%, RSR 0.85 vs. 0.93, and CCC of 0.43 vs. 0.29, respectively. The models developed in this study are applicable for predicting N excretion in beef cattle across a broad spectrum of dietary compositions and animal genotypes in South America. The univariate model using DMI as a predictor is recommended for fecal N prediction, while the univariate model using NI is recommended for predicting urinary and manure N excretion because the use of more complex models resulted in little to no benefits. However, it may be more useful to consider more complex models that incorporate nutrient intakes and diet composition for decision-making when N excretion is a factor to be considered. Three extant equations evaluated in this study have the potential to be used in tropical conditions typical of South America to predict fecal N excretion with good precision and accuracy. However, none of the extant equations are recommended for predicting urine or manure N excretion because of their high RMSE, and low precision and accuracy.

Venom Composition of Neglected Bothropoid Snakes from the Amazon Rainforest: Ecological and Toxinological Implications.

Snake venoms have evolved in several families of Caenophidae, and their toxins have been assumed to be biochemical weapons with a role as a trophic adaptation. However, it remains unclear how venom contributes to the success of venomous species for adaptation to different environments. Here we compared the venoms from Bothrocophias hyoprora, Bothrops taeniatus, Bothrops bilineatus smaragdinus, Bothrops brazili, and Bothrops atrox collected in the Amazon Rainforest, aiming to understand the ecological and toxinological consequences of venom composition. Transcriptomic and proteomic analyses indicated that the venoms presented the same toxin groups characteristic from bothropoids, but with distinct isoforms with variable qualitative and quantitative abundances, contributing to distinct enzymatic and toxic effects. Despite the particularities of each venom, commercial Bothrops antivenom recognized the venom components and neutralized the lethality of all species. No clear features could be observed between venoms from arboreal and terrestrial habitats, nor in the dispersion of the species throughout the Amazon habitats, supporting the notion that venom composition may not shape the ecological or toxinological characteristics of these snake species and that other factors influence their foraging or dispersal in different ecological niches.

Comprehensive conservation assessments reveal high extinction risks across Atlantic Forest trees.

Biodiversity is declining globally, yet many biodiversity hotspots still lack comprehensive species conservation assessments. Using multiple International Union for Conservation of Nature (IUCN) Red List criteria to evaluate extinction risks and millions of herbarium and forest inventory records, we present automated conservation assessments for all tree species of the Atlantic Forest biodiversity hotspot, including ~1100 heretofore unassessed species. About 65% of all species and 82% of endemic species are classified as threatened. We rediscovered five species classified as Extinct on the IUCN Red List and identified 13 endemics as possibly extinct. Uncertainties in species information had little influence on the assessments, but using fewer Red List criteria severely underestimated threat levels. We suggest that the conservation status of tropical forests worldwide is worse than previously reported.

Deciphering Divergent Trypanosomatid Nuclear Complexes by Analyzing Interactomic Datasets with AlphaFold2 and Genetic Approaches.

Acetylation signaling pathways in trypanosomatids, a group of early branching organisms, are poorly understood due to highly divergent protein sequences. To overcome this challenge, we used interactomic datasets and AlphaFold2 (AF2)-multimer to predict direct interactions and validated them using yeast two and three-hybrid assays. We focused on MORF4 related gene (MRG) domain-containing proteins and their interactions, typically found in histone acetyltransferase/deacetylase complexes. The results identified a structurally conserved complex, TcTINTIN, which is orthologous to human and yeast trimer independent of NuA4 for transcription interaction (TINTIN) complexes; and another trimeric complex involving an MRG domain, only seen in trypanosomatids. The identification of a key component of TcTINTIN, TcMRGBP, would not have been possible through traditional homology-based methods. We also conducted molecular dynamics simulations, revealing a conformational change that potentially affects its affinity for TcBDF6. The study also revealed a novel way in which an MRG domain participates in simultaneous interactions with two MRG binding proteins binding two different surfaces, a phenomenon not previously reported. Overall, this study demonstrates the potential of using AF2-processed interactomic datasets to identify protein complexes in deeply branched eukaryotes, which can be challenging to study based on sequence similarity. The findings provide new insights into the acetylation signaling pathways in trypanosomatids, specifically highlighting the importance of MRG domain-containing proteins in forming complexes, which may have important implications for understanding the biology of these organisms and developing new therapeutics. On the other hand, our validation of AF2 models for the determination of multiprotein complexes illuminates the power of using such artificial intelligence-derived tools in the future development of biology.

Odd-chain fatty acids as an alternative method to predict ruminal microbial nitrogen flow of feedlot Nellore steers fed grain-based diets supplemented with different nitrogen sources.

This study aimed to evaluate the use of total odd-chain fatty acids (OCFA) as a marker to estimate microbial nitrogen flow (MicN) and calculate the efficiency of microbial nitrogen synthesis (EMNS) in Nellore steers fed high-concentrate diets supplemented with different nitrogen supplements (NS). Ruminally and duodenally cannulated Nellore steers (n = 6; 354 ± 12 kg) were used in a 6 × 6 repeated switchback design balanced for residual effects. Treatments were arranged in a 3 × 3 factorial of three nitrogen (N) supplements (urea plus soybean meal; corn gluten meal; dried distillers' grains plus solubles) and three microbial markers (OCFA; double-labeled urea, 15N; microbial nucleic acid bases, MNAB). The total mixed ration was composed of fresh chopped sugarcane as the forage source in an 83:17 concentrate: forage ratio (dry matter basis). Linear regression was used to develop predictions of MicN from OCFA using 15N and MNAB as response variables. Microbial N flow was underestimated by the MNAB marker compared to 15N. Neither NS nor their respective interactions with the marker methods (MM) affected MicN or EMNS (P > 0.05). However, MicN was different for 15N and MNAB (P > 0.001 for both treatments). Marker methods affected EMNS in all energetic bases (total digestible carbohydrates P < 0.001; rumen-fermentable carbohydrates P < 0.001; organic matter truly degradable in the rumen P < 0.001). Equations that utilized OCFA as a regressor to predict MicN under different MM resulted in good fits of the data as observed by the coefficient of determination (R2; 15N = 0.78; MNAB = 0.69). Microbial N flow estimated from OCFA was overpredicted (15N by 7.46%; MNAB by 4.30%) compared with observed values. The OCFA model presented a small slope bias when methodological validation was applied (15N = 0.96%; MNAB = 3.90%), ensuring reliability of the proposed alternative method. Based on the conditions of this experiment, OCFA may be a suitable alternative to other methods that quantify MicN under different dietary conditions.

Nutritional strategies that maximize microbial nitrogen supply to the small intestine may improve cattle performance. Nevertheless, in vivo quantification generally requires sensitive or expensive methods and often yields highly variable results. In the present work, we investigated the use of duodenal odd-chain fatty acids (OCFA) as an alternative method to predict microbial nitrogen flow (MicN) and calculated its efficiency on different energetic bases under different dietary nitrogen supplements. We utilized total OCFA flow (TOCFAf) to predict MicN by two well-established conventional methods: 1) 15N, considered the gold standard and 2) microbial nucleic acid bases. Models presented a positive relationship between TOCFDf and response variables, and under validation, both demonstrated low estimation bias. Under the conditions of this experiment, OCFA appeared to serve as an alternative marker to quantify ruminal MicN for beef cattle.

Short-Term Adaptation of Dairy Cattle Production Parameters to Individualized Changes in Dietary Top Dress.

Immediate and short-term changes in diet composition can support individualized, real-time interventions in precision dairy production systems, and might increase feed efficiency (FE) of dairy cattle in the short-term. The objective of this study was to determine immediate and short-term effects of changes in diet composition on production parameters of dairy cattle fed varying amounts of top dressed commodities. A 4 × 4 replicated Latin square design was used to evaluate responses of twenty-four Holstein cows fed either no top dress (Control) or increasing amounts of: corn grain (CG), soybean meal (SBM), or chopped mixed grass hay (GH) top dressed on a total mixed ration (TMR) over four, 9-day periods. Throughout each period, top dressed commodities were incrementally increased, providing 0% to 20% of calculated net energy of lactation (NEL) intake. Measured production responses were analyzed for each 9-d period using a mixed-effects model considering two different time ranges. Samples collected from d 3 and 4 and from d 7 and 8 of each period were averaged and used to reflect "immediate" vs. "short-term" responses, respectively. In the immediate response time frame, control fed cows had lower milk yield, milk fat yield, and milk true protein yield than CG and SBM supplemented animals but similar responses to GH supplemented animals. Milk fat and protein percentages were not affected by top dress type in the immediate term. In the short-term response time-frame, GH supplemented animals had lower DMI and milk fat yield than all other groups. Control and GH supplemented cows had lower milk yield than CG and SBM fed cows. In the immediate response time frame, FE of SBM supplemented cows was superior to other groups. In the short-term time frame, FE of GH and SBM groups was improved over the control group. Results suggest that lactating dairy cows show rapid performance responses to small (<20% NEL) changes in dietary composition, which may be leveraged within automated precision feeding systems to optimize efficiency of production. Before this potential can be realized, further research is needed to examine integration of such strategies into automatic feeding systems and downstream impacts on individual animal FE and farm profitability.

A phase 2 randomized clinical trial of abiraterone plus ADT, apalutamide, or abiraterone and apalutamide in patients with advanced prostate cancer with non-castrate testosterone levels (LACOG 0415).

BACKGROUND: Androgen deprivation therapy (ADT) combined with apalutamide, abiraterone acetate plus prednisone, enzalutamide, or docetaxel are the standard treatments for advanced castration-sensitive prostate cancer (CSPC). We investigated ADT-free alternatives for advanced CSPC. PATIENTS AND METHODS: LACOG 0415 is a phase 2, open-label, non-comparative, randomized trial. Patients with advanced CSPC were randomized (1:1:1) to receive goserelin plus abiraterone acetate and prednisone (ADT plus AAP arm), apalutamide (APA arm), or apalutamide plus abiraterone acetate and prednisone (APA plus AAP arm). The primary endpoint was the proportion of patients with PSA of ≤0.2 ng/mL at week 25 in the modified intention-to-treat population. Safety analyses were performed in all patients with at least one dose of the study drug. RESULTS: Of 128 randomized patients, 120 patients were evaluable for PSA response at week 25; 17.2% had a high-risk biochemical recurrence, 8.6% had locally advanced disease, and 74.2% had distant metastases. At week 25, PSA of ≤0.2 ng/mL was observed in 75.6% (95%CI 59.7%-87.6%), 60.0% (95%CI 43.3%-75.1%), and 79.5% (95%CI 63.5%-90.7%) of patients in ADT plus AAP, APA, and APA plus AAP arms, respectively. PSA decline of ≥80% was observed in 100%, 90.0%, and 97.4%, respectively. Grade 3-4 AEs were observed in 31.0%, 21.4% and 36.4%, respectively. Testosterone levels increased significantly in the APA arm and decreased significantly in ADT plus AAP and APA plus AAP arms. CONCLUSIONS: ADT-free alternatives provide a high PSA response in advanced CSPC, although the APA arm did not reach the expected rate of PSA of ≤0.2 ng/mL at week 25. These results warrant further investigation of ADT-free treatments as alternatives in advanced CSPC. SOURCE STUDY REGISTRATION: ClinicalTrials.govNCT02867020.

Variation in urea kinetics associated with ruminant species, dietary characteristics, and ruminal fermentation: A meta-analysis.

The objective of this meta-analysis was to quantitatively summarize variations in urea kinetics related to ruminant species, diet composition, and ruminal fermentation. A database of 31 studies measuring urea recycling kinetics were used to derive 2 sets of linear mixed-effects regression models. Study was used as a random intercept and regressions were weighted by 1 divided by the standard error of the mean observation. Models were compared, when appropriated, using the concordance correlation coefficient, root estimated variance associated with study (σˆs) and error (σˆe) and corrected Akaike information criterion values. From a dietary standpoint, most response variables were affected by measures reflecting dietary crude protein [(CP; e.g., N-NH3 or rumen-degradable protein (RDP)] and by variables reflecting dietary energy content [e.g., total digestible nutrients (TDN), dietary starch, or ruminal pH]. Dietary CP, N-NH3, and TDN typically had positive slopes on urea N entry rate (UER; g/d and g/kg0.75), whereas starch and TDN/RDP had negative slopes on UER (g/kg0.75). On the other hand, increasing TDN increased gastrointestinal entry rate (GER; g/kg0.75), whereas an opposite effect was observed for RDP. Increasing diet RDP content reduced the urea N returned to ornithine cycle (ROC; g/kg0.75) in most models. Ruminal variables also reflected the importance of N and energy supplies. Ruminal ammonia concentration significantly affected ROC (g/d and g/kg0.75), used for anabolism (UUA; g/kg0.75), ROC:GER, UUA:GER, and the incorporation of recycled urea N into microbial N relative to gastrointestinal entry rate of urea. Ruminal pH significantly affected GER:UER and ROC:GER ratios. Total digestible nutrients had a positive slope on UUA (g/kg0.75). Increasing the ratio of energy to protein (TDN:RDP) increased the GER:UER ratio, decreased the ROC:GER ratio, and increased the UUA:GER ratio and the incorporation of recycled urea N into microbial N relative to gastrointestinal entry rate of urea N. Comparison among models revealed that species was an important explanatory variable affecting most response variables. However, whether these differences are related to the intrinsic N metabolism of each species or due to the diet variation remains unclear. Understanding these differences could lead to improvements in N use efficiency in ruminant diets by formulating more precise low-N diets considering the particularities for each species.

Insights about resveratrol analogs against trypanothione reductase of Leishmania braziliensis: Molecular modeling, computational docking and in vitro antileishmanial studies.

In this work, we combined molecular modeling, computational docking and in vitro analysis to explore the antileishmanial effect of some resveratrol analogs (ResAn), focusing on their pro-oxidant effect. The molecular target was the trypanothione reductase of Leishmania braziliensis (LbTryR), an essential component of the antioxidant defenses in trypanosomatid parasites. Three-dimensional structures of LbTryR were modeled and molecular docking studies of ResAn1-5 compounds showed the following affinity: ResAn1 > ResAn2 > ResAn4 > ResAn5 > ResAn3. Positive correlation was observed between these compounds' affinity to the LbTryR and the IC50 values against Leishmania sp (ResAn1 < ResAn2 < ResAn4), which allows for TryR being considered an important target for them. As the compound ResAn1 showed the best antileishmanial activity, and docking studies showed its high affinity for NADP binding site (NS) of TryR, plus having been able to induce ROS production in L. braziliensis promastigotes treated, ResAn1 probably occupies NS interfering in the electron transfer processes responsible for the catalytic reaction. The in silico prediction of ADMET properties suggests that ResAn1 may be a promising drug candidate with properties to cross biological membranes and high gastrointestinal absorption, not violating Lipinski's rules. Ultimately, the antileishmanial effect of ResAn can be associated with a pro-oxidant effect which, in turn, can be exploited as an antimicrobial agent. Communicated by Ramaswamy H. Sarma.

Corrigendum: Two Consecutive Days of Extreme Conditioning Program Training Affects Pro and Anti-inflammatory Cytokines and Osteoprotegerin without Impairments in Muscle Power.

[This corrects the article DOI: 10.3389/fphys.2016.00260.].

Evaluation of an inexpensive needle test for the diagnosis of phosphorus deficiency and management of phosphorus supplementation for cattle: A multiple case study.

The needle test (NT) is a point-of-care test developed in Brazil to evaluate the Phosphorus (P) status in cattle. Based on bone resistance, the NT is a very inexpensive method which allows the diagnosis of any degree of P deficiency in a fast and simple way in vivo and directly on farm. The NT measures three levels of resistance in the transverse process (TP) of the lumbar vertebrae: a) TP that are impenetrable and result in warping of the needle (P healthy animals); b) TP offering some resistance to the penetration (animals with subclinical P deficiency); and c) TP which has minimal resistance to penetration (clinical P deficiency). This manuscript presents results from a series of case studies to evaluate the hypothesis that the NT could be used to assess P status in cattle and assesses the usefulness of results to support decision making on mineral supplementation strategies for grazing cattle. The NT was able to detect the changes in the resistance patterns of the TP, as there was reduction or elevation of P levels in the mineral mixtures. The NT was useful to assist in decision-making for adoption of mineral supplementation strategies better suited for each farm, helping farmers to save money and avoid unnecessary waste of P.

Bio-economic evaluation of a reduced phosphorus supplementation strategy for a cow-calf system in Brazil: a case study.

Fertility, weight of calves at weaning, and the economic aspects of a breeding herd receiving mineral supplements containing 75 or 12.5 g of phosphorus (P)/kg were measured from 2013 to 2016. No differences in reproduction parameters or weight at weaning were found before and after the adoption of the new scheme of mineral supplementation. Before the study, the annual cost with the formula containing more P was equivalent to 29.3 weaned beef calves; after the P reduction, the annual cost was equivalent to 2.2 to 6.8 weaned calves. After 3 years of supplementation with 12.5 g P/kg no signs of P deficiency were observed. The clinical-nutritional diagnosis of the herd indicated no cause-effect of P content of mineral supplements upon fertility or performance of healthy cows, demonstranting that the adequate forage allowance was enough to meet most P required by the cows.

A simple and fast sampling method for chemical analyses and densitometry of bones through rib biopsies in cattle / Uma técnica simples e rápida de amostrar costelas para análises químicas e densitométricas por meio de biópsias em bovinos

We developed and evaluated a fast and simple method to obtain suitable bone samples for densitometry and chemical analysis through biopsies of the 12th rib of cattle. The postoperative recovery, dry matter intake (DMI) and average daily weight gain (ADG) was evaluated in 36 Nellore steers, nine of which were randomly selected for the control group and 27 others were rib biopsied. Every 30 days, rib biopsy was performed in nine steers, using a corded-electric pistol-grip drill coupled with a hole saw of a 3mm diameter pilot drill bit. This rib biopsy technique provided a suitable sample obtained in a fast way and allowed the surgeon to work alone with the animal slightly sedated and restrained in the crush. Dry matter intake (DMI) was not affected in biopsied animals. At the end of the experimental period (116 days) the average daily weight gain (ADG) was similar in the steers biopsied or not. The described method provided rib samples from cattle suitable for densitometry and chemical analysis of bone tissue without effects on health and performance. This information could greatly increase the accuracy for the diagnosis of phosphorus deficiency in cattle raised on pasture and allow the evaluation of bone metabolism in experimental animals.(AU)

No presente estudo foi desenvolvida uma técnica para se obter, de forma rápida e simples, amostras da 12a costela bovina por meio de biópsias. Avaliou-se a recuperação pós-operatória (durante 15 dias), o consumo de matéria seca (CMS) e o ganho de peso diário (GMD) de 36 novilhos Nelores, sendo nove animais controles e 27 submetidos à biópsia. A cada 30 dias biópsias de costelas foram realizadas em nove animais, usando uma furadeira elétrica acoplada a uma serra-copo com uma broca-guia de 3mm de diâmetro. Esta técnica de biópsia permitiu obter amostras ósseas de forma rápida, com o cirurgião operando sozinho e com os animais levemente sedados e em estação. Ao término do experimento (116 dias) o CMS e o GMD não foram afetados pelo procedimento cirúrgico. As amostras obtidas foram adequadas para exames radiográficos e subsequentes análises químicas. O conjunto de informações adquiridas com a técnica de biópsia de costelas permite aumentar a exatidão no diagnóstico da deficiência de fósforo em bovinos criados em pastagens e também realizar estudos sobre metabolismo ósseo em animais experimentais.(AU)

Serum Klotho (but not haplotypes) associate with the post-myocardial infarction status of older adults

OBJECTIVES: The number of deaths from vascular diseases is incredibly high worldwide, and reliable markers for major events are still needed. The current cross-sectional study investigated the association of Klotho haplotypes and Klotho serum levels with classic risk factors and a clinical history of vascular events. METHODS: Clinical, anthropometric, biochemical and nutritional assessments were conducted with 168 older adults, complemented by genotyping (rs9536314 and rs9527025) and the detection of serum Klotho (ELISA). RESULTS: Klotho levels and haplotypes did not associate with most classic risk factors for vascular events, including markers such as C-reactive protein and homocysteine. A positive association was only found between Klotho levels and the previous occurrence of a myocardial infarction by both correlational (p=0.006) and variance analyses (p<0.001), and these associations were independent of the context. CONCLUSION: Our results suggest that serum Klotho is higher in individuals with a clinical history of myocardial infarction but not with a history of coronary artery disease or stroke. None of the Klotho haplotypes were associated with the variables investigated herein.

Two Consecutive Days of Crossfit Training Affects Pro and Anti-inflammatory Cytokines and Osteoprotegerin without Impairments in Muscle Power.

The aim of this study was to investigate the effects of two consecutive Crossfit® training sessions (24 h apart) designed to enhance work-capacity that involved both cardiovascular and muscular exercises on cytokines, muscle power, blood lactate and glucose. Nine male members of the CrossFit® community (age 26.7 ± 6.6 years; body mass 78.8 ± 13.2 kg; body fat 13.5 ± 6.2%; training experience 2.5 ± 1.2 years) completed two experimental protocols (24 h apart): (1) strength and power exercises, (2) gymnastic movements, and (3) metabolic conditioning as follows: 10 min of as many rounds as possible (AMRAP) of 30 double-unders and 15 power snatches (34 kg). The same sequence as repeated on session 2 with the following metabolic conditioning: 12 min AMRAP of: row 250 m and 25 target burpees. Serum interleukin-6 (IL-6), IL-10, and osteoprotegerin were measured before, immediately post and 24 h after workout of the day (WOD) 1, immediately post, 24 and 48 h after WOD 2. Peak and mean power were obtained for each repetition (back squat with 50% of 1 repetition maximum) using a linear position transducer measured before, immediately post and 24 h after WOD 1, immediately post and 24 h after WOD 2. Blood lactate and glucose were measured pre and immediately post WOD 1 and 2. Although both sessions of exercise elicited an significant increase in blood lactate (1.20 ± 0.41 to 11.84 ± 1.34 vs. 0.94 ± 0.34 to 9.05 ± 2.56 mmol/l) and glucose concentration (81.59 ± 10.27 to 114.99 ± 12.52 vs. 69.47 ± 6.97 to 89.95 ± 19.26 mg/dL), WOD 1 induced a significantly greater increase than WOD 2 (p ≤ 0.05). The training sessions elicited significant changes (p ≤ 0.05) in IL-6, IL-10 and osteoprotegerin concentration over time. IL-6 displayed an increase immediately after training WOD 1 [197 ± 109%] (p = 0.009) and 2 [99 ± 58%] (p = 0.045). IL-10 displayed an increase immediately after only WOD 1 [44 ± 52%] (p = 0.046), and decreased 24 and 48 h following WOD 2 (~40%; p = 0.018) as compared to pre-exercise values. Osteoprotegerin displayed a decrease 48 h following WOD 2 (~25%; p = 0.018) as compared with pre intervention. In conclusion, two consecutive Crossfit® training sessions increase pro/anti-inflammatory cytokines with no interference on muscle performance in the recovery period.

Serum Klotho (but not haplotypes) associate with the post-myocardial infarction status of older adults.

OBJECTIVES:: The number of deaths from vascular diseases is incredibly high worldwide, and reliable markers for major events are still needed. The current cross-sectional study investigated the association of Klotho haplotypes and Klotho serum levels with classic risk factors and a clinical history of vascular events. METHODS:: Clinical, anthropometric, biochemical and nutritional assessments were conducted with 168 older adults, complemented by genotyping (rs9536314 and rs9527025) and the detection of serum Klotho (ELISA). RESULTS:: Klotho levels and haplotypes did not associate with most classic risk factors for vascular events, including markers such as C-reactive protein and homocysteine. A positive association was only found between Klotho levels and the previous occurrence of a myocardial infarction by both correlational (p=0.006) and variance analyses (p<0.001), and these associations were independent of the context. CONCLUSION:: Our results suggest that serum Klotho is higher in individuals with a clinical history of myocardial infarction but not with a history of coronary artery disease or stroke. None of the Klotho haplotypes were associated with the variables investigated herein.

Tailored antihypertensive drug therapy prescribed to older women attenuates circulating levels of interleukin-6 and tumor necrosis factor-α.

OBJECTIVE: To test the hypothesis that antihypertensive drug therapy produces anti-inflammatory effects in clinical practice, this study investigated circulating levels of selected proinflammatory mediators (interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], and interferon-γ [INF-γ]) in response to multivariate drug directions for blood pressure (BP) control. METHODS: Prospective study involving 110 hypertensive, community-dwelling older women with different metabolic disorders. A short-term BP-lowering drug therapy was conducted according to current Brazilian guidelines on hypertension, and basal cytokine levels were measured before and after intervention. RESULTS: Interventions were found to represent current hypertension-management practices in Brazil and corresponded to a significant reduction in systolic and diastolic BP levels in a whole-group analysis, as well as when users and nonusers of the most common therapeutic classes were considered separately. Considering all patients, mean IL-6 and TNF-α levels showed a significant decrease in circulating concentrations (P<0.01) at the endpoint compared with baseline, whereas the mean INF-γ level was not significantly different from baseline values. In separate analyses, only users of antagonists of the renin-angiotensin system and users of diuretics exhibited the same significant treatment-induced reduction in serum IL-6 and TNF-α observed in the whole group. CONCLUSION: Our data demonstrates that a clinically guided antihypertensive treatment is effective in reversing the low-grade proinflammatory state of serum cytokines found in postmenopausal women and support extracardiac benefits from diuretics and renin-angiotensin system antagonists.

Interleukin-6 -174G/C gene polymorphism affects muscle damage response to acute eccentric resistance exercise in elderly obese women.

The IL-6 gene polymorphism has been associated with disease prevalence and different physiological responses to exercise. Eccentric resistance exercise (ERE) is considered a nonpharmacological tool to prevent the chronic degenerative profile associated with aging and obesity. Consequently, the aim of the present study was to investigate the influence of IL-6 -174G/C polymorphism on acute interleukin-6 (IL-6) and creatine kinase (CK) temporal response to ERE in elderly obese women. Ninety women completed seven sets of ten repetitions (eccentric only) of an acute ERE session at 110% of the ten repetitions maximum (10RM). IL-6 genotypes displayed no difference at baseline. ERE induced changes in CK concentration over time occurred only in the GG group, F(2.619, 136.173)=5.199, p=0.003, with CK activity increased from 106.8±6.9 U/l pre-intervention to 122.7±11.2 U/l at 24 h and 131.9±14.4 U/l at 48 h post-exercise. IL-6 concentration in the GG group was lower than the CC/CG group only at 0 h post-exercise (3.78±0.58 pg/ml versus 6.51±1.91 pg/ml, p=0.030). Only the GG genotype group had higher CK activity 24-48 h following ERE and greater CK integral values, while IL-6 activity over 48 h was higher in the CC/CG genotype group. In conclusion, IL-6 genotype affects CK and IL-6 in response to ERE. It is of interest that the ERE protocol induced an elevation in CK, indicating possible muscle damage without exacerbating IL-6 and CK for the GG genotype.

Cytokine gene polymorphisms and Alzheimer's disease in Brazil.

BACKGROUND: Single-nucleotide polymorphisms in genes encoding immunological mediators can affect the biological activity of these molecules by regulating transcription, translation, or secretion, modulating the genetic risk of inflammatory damage in Alzheimer's disease (AD). Nonetheless, the Brazilian contingent is highly admixed, and few association trials performed herein with AD patients have considered genetic ancestry estimates as co-variables when investigating markers for this complex trait. METHODS: We analyzed polymorphisms in 10 inflammatory genes and compared the genotype distribution across outpatients with late-onset AD and noncognitively impaired subjects from Midwest Brazil under a strict criterion, and controlling for ancestry heritage and ApoE genotype. RESULTS: Our findings show an almost 40% lower chance of AD (p = 0.004) among homozygotes of the IL10 -1082A allele (rs1800896). Dichotomization to ApoE and mean ancestry levels did not affect protection, except among those with greater European or minor African heritage. CONCLUSION: The IL10 locus seems to affect the onset of AD in a context sensitive to the genetic ancestry of Brazilian older adults.