Role of the placenta in developmental programming: Observations from models using large animals.

Developmental programming, which proposes that "insults" or "stressors" during intrauterine or postnatal development can have not only immediate but also long-term consequences for healthy and productivity, has emerged as a major biological principle, and based on studies in many animal species also seems to be a universal phenomenon. In eutherians, the placenta appears to be programmed during its development, which has consequences for fetal growth and development throughout pregnancy, and likewise has long-term consequences for postnatal development, leading to programming of organ function of the offspring even into adulthood. This review summarizes our current understanding of the placenta's role in developmental programming, the mechanisms involved, and the challenges remaining.

Effect of feeding a low-vitamin A diet on carcass and production characteristics of steers with a high or low propensity for marbling.

Our research group demonstrated that vitamin A restriction affected meat quality of Angus cross and Simmental steers. Therefore, the aim of this study is to highlight the genotype variations in response to dietary vitamin A levels. Commercial Angus and Simmental steers (n = 32 per breed; initial BW = 337.2 ± 5.9 kg; ~8 months of age) were fed a low-vitamin A (LVA) (1017 IU/kg DM) backgrounding diet for 95 days to reduce hepatic vitamin A stores. During finishing, steers were randomly assigned to treatments in a 2 × 2 factorial arrangement of genotype × dietary vitamin A concentration. The LVA treatment was a finishing diet with no supplemental vitamin A (723 IU vitamin A/kg DM); the control (CON) was the LVA diet plus supplementation with 2200 IU vitamin A/kg DM. Blood samples were collected at three time points throughout the study to analyze serum retinol concentration. At the completion of finishing, steers were slaughtered at a commercial abattoir. Meat characteristics assessed were intramuscular fat concentration, color, Warner-Bratzler shear force, cook loss and pH. Camera image analysis was used for determination of marbling, 12th rib back fat and longissimus muscle area (LMA). The LVA steers had lower (P < 0.001) serum retinol concentration than CON steers. The LVA treatment resulted in greater (P = 0.03) average daily gain than the CON treatment, 1.52 and 1.44 ± 0.03 kg/day, respectively; however, there was no effect of treatment on final BW, DM intake or feed efficiency. Cooking loss and yield grade were greater and LMA was smaller in LVA steers (P < 0.05). There was an interaction between breed and treatment for marbling score (P = 0.01) and percentage of carcasses grading United States Department of Agriculture (USDA) Prime (P = 0.02). For Angus steers, LVA treatment resulted in a 16% greater marbling score than CON (683 and 570 ± 40, respectively) and 27% of LVA Angus steers graded USDA Prime compared with 0% for CON. Conversely, there was no difference in marbling score or USDA Quality Grades between LVA and CON for Simmental steers. In conclusion, feeding a LVA diet during finishing increased marbling in Angus but not in Simmental steers. Reducing the vitamin A level of finishing diets fed to cattle with a high propensity to marble, such as Angus, has the potential to increase economically important traits such as marbling and quality grade without negatively impacting gain : feed or yield grade.

Development of an equation to predict net protein requirements for the growth of Zebu beef cattle.

The accurate estimation of protein requirements for beef cattle is a key factor in increasing livestock profitability and decreasing the environmental impacts of excessive N excretion due to mismatching between assumed requirements and diet formulation. A meta-analysis was conducted to evaluate and validate a new equation to predict the net protein requirements for growth (NPg) of Zebu beef cattle. For the development of the new approach, a database of 552 observations comprised of bulls, steers, and heifers of different genetic groups (Zebu, beef crossbreed, and dairy crossbreed) was assembled. The new approach was evaluated and compared to current models devised by the international nutrient requirements system committees (Agricultural Research Council, 1980; Beef Cattle Nutrient Requirements Model, 2016; BR-CORTE, 2016) to predict NPg. The model evaluation was performed through the model evaluation system (version 3.1.16) using an independent data set (n = 177 observations). An equation was considered the best estimator of NPg if the following conditions were met: (1) the intercept and slope of the regression between ordinary residues and/or predicted NPg values must have been equal to zero and one, respectively; and (2) the greatest concordance correlation coefficient (CCC) and determination coefficient (R), and lowest mean squared error of prediction (MSEP) were attained. Based on the regression models of the observed v. predicted NPg of Zebu beef cattle, both the new approach and that of the ARC (1980) correctly estimated NPg, since the intercept and slope were not different (P > 0.05) from zero and one, respectively. Additionally, the new approach's determination coefficient was the greatest and the closest to one. The fact that the new model achieved a higher CCC and lower MSEP than the existing models indicated its superior reproducibility and accuracy. The equations proposed by BR-CORTE (2016) and the BCNRM (2016) did not correctly estimate NPg in that the intercept and slope were different (P < 0.01) from zero and one, respectively. Thus, the equations proposed by the new approach and the ARC (1980) accurately and precisely estimated NPg and are recommended for Zebu cattle. Furthermore, the inclusion of equivalent empty BW (EQEBW) in the new approach improves the estimation of NPg. We suggest the use of the following equation to calculate NPg for Zebu beef cattle: NPg = 176.01 × EBG - 0.381 × EQEBW0.75 × EBG1.035 (R = 0.80 and CCC = 0.75); where NPg = net protein requirements for growth, EBG = empty body gain, and EQEBW = equivalent empty BW.

Cytotoxicity profiling of deep eutectic solvents to human skin cells.

The tailor-made character of deep eutectic solvents (DES) turns them very attractive to be used in several applications, including in health-related areas such as pharmaceutical, nutraceutical, and cosmetic industries. However, although DES has been touted as "green" solvents, several works proved that their potential toxicity should not be neglected. Using the premise of DES applicability in the cosmetic and pharmaceutical sectors, we chose two cell lines to work as a skin model (keratinocytes HaCaT and tumor melanocytes MNT-1), to assess DES cytotoxicity. The effect of three different hydrogen bond acceptors (HBA) ([Chol]Cl, [N1111]Cl and [N4444]Cl) and three different hydrogen bond donors (HBD) (hexanoic and butanoic acid, ethylene glycol, 1-propanol and urea) were evaluated through a common viability assay (MTT assay). Results were promising since [Chol]Cl and [N1111]Cl- based DES showed good biocompatibility for the tested cells. [N4444]Cl-based DES, however, showed cytotoxicity for both cell lines, with the HBA being the driver of the toxicity. Interestingly, some compounds increased cell viability in the HaCaT cell line, namely [Chol]Cl, ethylene glycol, hexanoic acid, urea, and all [Chol]Cl and [N1111]Cl-based DES and should be considered as targets for future studies. These results highlight their possible use in cosmetic or pharmaceutical formulations.

Energy and protein requirements for growth of Holstein × Gyr heifers.

There is little information regarding the nutritional requirements for dairy heifers, leading the majority of nutrient requirement systems to consider dairy heifers to be similar to beef heifers. Therefore, we evaluated the muscle protein metabolism and physical and chemical body composition of growing Holstein × Gyr heifers and estimated the energy and protein requirements. We performed a comparative slaughter experiment with 20 Holstein × Gyr heifers at an initial body weight of 218 ± 36.5 kg and an average age of 12 ± 1.0 months. Four heifers were designated as the reference group, and the 16 remaining heifers were fed ad libitum. The 16 heifers were distributed using a completely randomized design in a 2 × 2 factorial arrangement with two roughages (corn silage or sugarcane) and two concentrate levels (30 or 50%) for 112 days. Greater (p < 0.05) values for fractional rates of muscle protein synthesis, degradation and accretion were observed for heifers that were fed 50% concentrate. The following equations were obtained to estimate the net energy for gain (NEg ) and net protein for gain (NPg ): NEg (Mcal/day) = 0.0685 × EBW0.75  × EBWG1.095 and NPg (g/day) = 203.8 × EBWG - 14.80 × RE, respectively, in which EBW is the empty body weight, EBWG is the empty body weight gain and RE is the retained energy. We concluded that increased rates of protein turnover are achieved when a greater quality diet is provided. In the future, these results can be used to calculate the nutritional requirements for growth of Holstein × Gyr heifers after equation validation rather than using the recommendations provided by other systems, which use values developed from beef heifers, to determine the nutritional requirements of dairy cattle.

Does microbial nitrogen contamination affect the estimation of crude protein degradability of concentrate feeds?

The effects of microbial contamination (MC) on CP degradability of concentrate feeds are still controversial. Therefore, the aim of this study was to use N to estimate the impact of MC on estimations of CP fractions (the soluble fraction of CP [a], the insoluble but potentially degradable fraction of CP [b], and the rate of digestion of fraction b [kd]) of concentrate feeds. Twelve types of feed were evaluated: 6 energy concentrates-wheat bran ( L.), rice meal ( L.), ground corn ( L.), ground sorghum ( Pers.), ground corn cob ( L.), and soybean hulls [ (L.) Merr.]-and 6 protein concentrates-cottonseed meal ( L.), soybean meal [ (L.) Merr.], ground bean ( L.), peanut meal ( L.), sunflower meal ( L.), and corn gluten meal ( L.). The feeds were divided into 4 groups and were incubated in the rumen of 4 crossbred bulls. The samples were incubated for 0, 2, 4, 8, 16, 24, 48, and 72 h. To estimate the MC of the incubated residues, the ruminal bacteria were labeled with N via continuous intraruminal infusion of (NH)SO. There was no difference ( = 0.738) between corrected and uncorrected parameters a, b, and kd for all feeds that were evaluated. All of the feed tests followed an exponential model of degradation, and the model fitted well to the data, except for corn gluten meal, probably because the maximum incubation time that was used (72 h) was not long enough to allow for an accurate estimation of the degradation profile. Therefore, correction of ruminal protein degradation to MC is irrelevant with regards to the concentrates that were studied.

Effects of day of gestation and feeding regimen in Holstein × Gyr cows: II. Maternal and fetal visceral organ mass.

This study investigated the influence of day of gestation (DG) and feeding regimens (FR) on maternal and fetal visceral organ mass in Holstein × Gyr cows. Forty-four pregnant multiparous Holstein × Gyr cows with an average initial body weight of 480±10.1 kg and an average initial age of 5±0.5 yr were allocated to 1 of 2 FR: ad libitum (AL; n=20) or maintenance level (ML; n=24). Maintenance level was considered to be 1.15% of body weight (dry matter basis) and met 100% of the energy requirements; AL provided 190% of the total net energy requirements. Cows were individually fed a corn silage and concentrate-based diet composed of 93% roughage and 7% concentrate (dry matter basis) as a total mixed ration twice daily. Pregnant cows were slaughtered at 4 DG: 139 (n=11), 199 (n=11), 241 (n=11), and 268 (n=11) d, which was followed by necropsy. Mass of heart, liver, and gastrointestinal tract was heavier in AL- than in ML-fed cows. Mammary gland mass was heavier in AL- than in ML-fed cows, and the heaviest mass was observed at 268 d of gestation. Feeding regimen did not influence fetal body weight in this study. The majority of the visceral organ masses were similar in fetuses from cows fed AL or ML. These data indicate that maternal feed restriction does not affect the development of most fetal organs or fetal development; however, some maternal organs are affected by the FR provided. Moreover, the negative effect on mammary gland mass caused by ML feeding will probably not affect the subsequent lactation because the crude protein concentration in the mammary gland increased with ML feeding. However, we suggest that the AL diet in pregnant dry cows should be provided with caution because the amount of fat in the mammary gland increased at 268 d of gestation.

Assessment of genotoxic, cytotoxic, and protective effects of Salacia crassifolia (Mart. Ex. Schult.) G. Don. stem bark fractions in mice.

Salacia crassifolia (Mart. Ex. Schult.) G. Don., popularly known in Brazil as "bacupari", "cascudo", and "saputá", is a shrub of the Celastraceae family that is unique to the Brazilian Cerrado region. In folk medicine, this plant has been mainly used to treat skin cancer and gastric ulcers. In the present study, the genotoxic, cytotoxic, antigenotoxic, and anticytotoxic effects of S. crassifolia stem bark fractions (hexane, ethyl acetate, and hydroalcoholic extracts) were evaluated using the mouse bone marrow micronucleus test. Our results showed that none of the S. crassifolia fractions led to a significant increase in the frequency of micronucleated polychromatic erythrocytes (MNPCE) (P > 0.05), suggesting the absence of genotoxicity. In the antigenotoxicity assessment, a significant decrease in the MNPCE frequency was observed in all fractions of this plant (P < 0.05), demonstrating its protective action against genotoxicity induced by mitomycin C (MMC), which was used as the positive control. Only the hexane fraction of S. crassifolia significantly decreased the poly- and normochromatic erythrocyte ratio (PCE/NCE) in all doses tested (P < 0.05), demonstrating its cytotoxic activity. In association with MMC, both ethyl acetate and hydroalcoholic fractions significantly increased the PCE/NCE ratio in almost all doses tested (P < 0.05), demonstrating the protective action of S. crassifolia against the cytotoxic effect of the positive control. In contrast, the hexane fraction presented a significant decrease in the PCE/NCE ratio in all treatments (P < 0.05), demonstrating an increase in this plant's cytotoxicity in mouse bone marrow cells.

Gênero Pimenta: aspectos botânicos, composição química e potencial farmacológico / Pimenta genus: botanical aspects, chemical composition and pharmacological potential

A família Myrtaceae possui representantes de grande interesse medicinal e o gênero Pimenta é um dos que merecem destaque. A maioria das espécies desse gênero é nativa da América Central, com exceção da Pimenta pseudocaryophyllus (Gomes) L. R. Landrum, nativa nas regiões centro-oeste e sudeste do Brasil. O presente estudo teve como objetivo revisar aspectos botânicos, químicos e farmacológicos descritos na literatura sobre o gênero Pimenta. Os dados foram obtidos de artigos originais e revisões indexadas nas bases Periódicos Capes, ISI Web of Knowledge, Bireme e SciELO. As espécies desse gênero podem ser arbustivas ou arbóreas, possuem pelos unicelulares, folhas usualmente coriáceas, inflorescência em dicásio ou panícula e são distinguidas, principalmente, pela estrutura do ovário. As propriedades farmacológicas são conferidas, principalmente, pelos óleos essenciais que são constituídos, na maioria, por derivados fenilpropanóides, monoterpenos, aldeídos monoterpênicos e alcoóis monoterpênicos. Dentre as propriedades farmacológicas apresentadas por espécies desse gênero destacam-se as anti-hipertensivas, anti-inflamatórias, analgésicas, antimicrobianas e antioxidantes. Das quinze espécies de Pimenta conhecidas, a Pimenta dioica (L.) Merrill e a Pimenta racemosa (Miller) J. Moore são as espécies de maior importância econômica e, por esse motivo são as mais estudadas do ponto de vista químico e farmacológico.

The family Myrtaceae has representatives of great medical interest, and the genus Pimenta deserves attention. Most species of this genus are native to the Central America, except Pimenta pseudocaryophyllus (Gomes) L. R. Landrum, which is native to the Central-West and Southeast Brazilian Regions. This study aimed to review botanical, chemical and pharmacological aspects described in the literature for Pimenta genus. Information was obtained from original papers and reviews indexed in the databases "Periódicos Capes", ISI Web of Knowledge, "Bireme" and SciELO. This genus can present shrubs or trees, which have unicellular hairs, usually coriaceous leaves and dichasium or panicle inflorescence, and are mainly distinguished by the ovary structure. The pharmacological properties are mostly due to essential oils, mainly consisted of phenylpropanoid, monoterpene, monoterpenic aldehyde and alcohol derivatives. Among these properties, antihypertensive, anti-inflammatory, analgesic, antimicrobial and antioxidant ones are highlighted. Of the fifteen known Pimenta species, Pimenta dioica (L.) Merrill and Pimenta racemosa (Miller) J. Moore have the greatest economic importance and consequently have been the most chemically and pharmacologically studied.

Estudo técnico e econômico de um sistema de produção de leite com gado mestiço F1 Holandês-Zebu / Technical and economic evaluation on of a milk production system for F1 Holstein-Zebu cattle

Avaliaram-se a viabilidade técnica e a rentabilidade de um sistema de produção de leite com gado mestiço, mediante análise de custos e receitas da atividade e avaliação da rentabilidade. Os dados foram obtidos de uma unidade experimental da EPAMIG, situada no município de Felixlândia, MG, e referem-se a dois períodos iguais de um ano cada. As variáveis analisadas foram: rentabilidade nos períodos de análise, custo de cria do bezerro e sua importância sobre a receita da atividade. A viabilidade do sistema foi demonstrada pela rentabilidade de 20,2 por cento no ano 1 e 37,6 por cento no ano 2; a venda dos bezerros à desmama representou 25 por cento da receita total.

Exposure to mercury in pregnant women from Alta Floresta-Amazon basin, Brazil.

The region of Alta Floresta in the South of the Amazon basin, close to the Teles Pires River, was one of the main prospecting gold areas in the Amazon Basin until the beginning of the 1990s. The economic growth was accompanied by a considerable increase in the population, due to a massive influx of migrants from the southern region of the country. Women had an important role during that process. They worked in the "garimpos" in different activities, such as cooking or managing, where they were exposed mainly to indoor elemental mercury during burning of amalgam. They also worked in gold dealers' shops, where a great amount of amalgam was burned daily. Fish consumption was an important dietary protein source and also a possible exposure pathway, due to the high Hg concentrations reported in carnivorous species. The present study evaluates the mercury uptake and consequent risks involved for pregnant women from Alta Floresta at the end of the gold rush period. The survey included women at different pregnancy stages and it was supported by clinical exams, followed by an interview with a specific questionnaire. Mercury hair concentrations ranging from 0.05 to 8.2 microg/g were found among women, with 13% of them showing concentrations above 2 microg/g. According to the results, mean differences in hair mercury concentration were statistically higher for pregnant women if they had worked in gold mining areas, they had consumed alcohol, their husbands had worked as "garimpeiros," they ate fish, and/or they had malaria before and/or during pregnancy

Effects of ethanol and malnutrition on rat neuromotor development.

The objective of the present study was to determine whether there is a synergistic effect of malnutrition and ethanol exposure on neuromotor development. Ethanol (E) (6 g/kg) or sucrose (S) (isocaloric to ethanol) was administered by gavage to ad libitum-fed (A) and malnourished (M) pregnant rats on days 18, 19 and 20 of pregnancy. Malnutrition was produced by food restriction to 50% of control intake. At birth, the offspring were weighed and transferred to surrogate mothers. Performance in the rim-escape test and on the rotating rod were evaluated on days 19 and 28 of life, respectively. Development of the adult swimming pattern was also studied. The results indicated that: 1) malnutrition alone decreased birth weight (g) significantly (AE, 5.56 +/- 0.36; AS, 6.31 +/- 1.05; ME, 4.81 +/- 0.73; MS, 5.23 +/- 0.57); 2) a synergistic interaction between alcohol exposure and malnutrition was observed only in the rim escape test (percent of falling rats: AE, 9; AS, 5; ME, 24; MS, 5); 3) only malnutrition retarded development of swimming; 4) malnourished dams gained more weight (g) than controls during treatment with ethanol (AE, 2.6 +/- 8.4, N = 6; AS, 3.1 +/- 8.4, N = 4; ME, 23.0 +/- 6.3, N = 7; MS, 29.0 +/- 9.0, N = 8). These results indicate a possible synergistic action between malnutrition and ethanol on neuromotor development and point to the importance of ethanol as a calorie source for malnourished animals.

Effects of ethanol and malnutrition on rat neuromotor development

The objective of the present study was to determine whether there is a synergistic effect of malnutrition and ethanol exposure on neuromotor development. Ethanol (E) (6 g/kg) or sucrose (S) (isocaloric to ethanol) was administered by gavage to ad libitum-fed (A) and malnourished (M) pregnant rats on days 18, 19 and 20 of pregnancy. Malnutrition was produced by food restriction to 50 of control intake. At birth, the offspring were weighed and transferred to surrogate mothers. Performance in the rim-escape test and on the rotating rod were evaluated on days 19 and 28 of life, respectively. Development of the adult swimming pattern was also studied. The results indicated that: 1) malnutrition alone decreased birth weight (g) significantly (AE, 5.56 +/- 0.36; AS, 6.31 +/- 1.05; ME, 4.81 +/- 0.73; MS, 5.23 +/- 0.57); 2) a synergistic interaction between alcohol exposure and malnutrition was observed only in the rim escape test (percent of falling rats: AE, 9; AS, 5; ME, 24; MS, 5); 3) only malnutrition retarded development of swimming; 4) malnourished dams gained more weight (g) than controls during treatment with ethanol (AE, 2.6 +/- 8.4, N = 6; AS, 3.1 +/- 8.4, N = 4; ME, 23.0 +/- 6.3, N = 7; MS, 29.0 +/- 9.0, N = 8). These results indicate a possible synergistic action between malnutrition and ethanol on neuromotor development and point to the importance of ethanol as a calorie source for malnourished animals.

Clinical manifestations of hypervitaminosis A in human gingiva. A case report.

Periodontal inflammation caused by excessive doses of vitamin A was studied in a patient who had taken 200,000 international units daily for more than 6 months. Clinical manifestations of the disease disappeared when the use of vitamin A was interrupted. The role of vitamin A as a factor in periodontal inflammation is discussed.