RESUMO
Trace mineral (TM) source can potentially alter nutrient digestibility through effects on microbial populations. A meta-analysis was conducted to determine whether sulfate versus hydroxy (IntelliBond) sources of supplemental Cu, Zn, and Mn had any effect on dry matter intake (DMI), dry matter digestibility, and neutral detergent fiber (NDF) digestibility. All available cattle studies (8 studies, 12 comparisons) were used to estimate the effect size (hydroxy mean - sulfate mean). Factors included in the analysis were method of digestibility analysis (total collection, marker-based, or 24 h in situ), study design (randomized design or Latin square), beef (n = 5) versus dairy (n = 7) cattle, and days on treatment; these factors were retained when P < 0.05. Dry matter digestibility was increased by hydroxy TM in beef (1.64 ± 0.35 units) but not in dairy models (0.16 ± 0.13 units) relative to sulfate TM. The NDF digestibility increased significantly with hydroxy versus sulfate TM, but digestibility assessment method influenced this response. Studies using total collection or undigested NDF as a flow marker showed a significant increase (2.68 ± 0.40 units and 1.08 ± 0.31 units, respectively) in NDF digestibility for hydroxy versus sulfate TM; but studies utilizing 24-h in situ incubation did not detect any change (-0.03 ± 0.23 units). These observations may reveal differences in precision of measurement or may indicate mineral effects beyond the rumen; total collection is considered the gold standard method. Hydroxy TM did not affect DMI per animal or per unit of body weight relative to sulfate TM. In conclusion, feeding hydroxy versus sulfate TM does not appear to affect DMI but, depending on type of cattle and method of measurement, can increase dry matter digestibility and NDF digestibility, which may be explained by differences in solubility of the TM sources in rumen, differentially affecting fermentation.
Assuntos
Oligoelementos , Bovinos , Animais , Feminino , Oligoelementos/farmacologia , Sulfatos/metabolismo , Sulfatos/farmacologia , Dieta/veterinária , Fibras na Dieta/metabolismo , Digestão , Nutrientes , Rúmen/metabolismo , Fermentação , Ração Animal , LactaçãoRESUMO
OBJECTIVE: To determine the association between prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm (<28 weeks of gestation). DESIGN: The Extremely Low Gestational Age Newborn (ELGAN) Study, a prospective cohort. SETTING: Ten-year follow-up of extremely preterm infants born at 14 US hospitals between 2002 and 2004. METHODS: Prenatal tobacco smoke exposure was defined as a mother's report at enrolment of active (i.e. maternal) and passive smoking during pregnancy. Poisson regression with generalized estimating equations was used. Models adjusted for mother's age, race/ethnicity, education, insurance, pre-pregnancy body mass index, US region, multiple gestation and infant's sex; and in sensitivity analysis, gestational age at delivery and clinical subtype of preterm birth, given their classification as intermediate and non-confounding variables. MAIN OUTCOMES: Neurological impairment at 10 years, epilepsy, cerebral palsy and cognitive impairment. RESULTS: Of 1200 ELGAN study survivors, 856 were assessed at 10 years of age with neurological outcomes, of whom 14% (118/856) had active tobacco exposure during pregnancy and 24% (207/852) had passive tobacco exposure. Compared with children who were not exposed prenatally to tobacco, children exposed to active tobacco use during pregnancy had a higher risk of epilepsy (14% versus 5%; adjusted relative risk: 1.68, 95% CI 1.45-1.92). This risk remained after adjustment for gestational age at delivery and clinical subtype of preterm birth. Prenatal tobacco smoke exposure was not associated with other assessed neurological outcomes, including cerebral palsy and multiple measures of cognitive impairment. CONCLUSIONS: Among children born extremely preterm, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life. TWEETABLE ABSTRACT: Among infants born before 28 weeks of gestation, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life.
Assuntos
Paralisia Cerebral/epidemiologia , Epilepsia/epidemiologia , Lactente Extremamente Prematuro , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Paralisia Cerebral/induzido quimicamente , Criança , Estudos de Coortes , Epilepsia/induzido quimicamente , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estudos Prospectivos , Estados Unidos/epidemiologiaRESUMO
The Emergency Medical Retrieval and Transfer Service for Wales launched in 2015. This service delivers senior pre-hospital doctors and advanced critical care practitioners to the scene of time-critical life- and limb-threatening incidents to provide advanced decision-making and pre-hospital clinical care. The impact of the service on 30-day mortality was evaluated retrospectively using a data linkage system. The study included patients who sustained moderate-to-severe blunt traumatic injuries (injury severity score ≥ 9) between 27 April 2015 and 30 November 2018. The association between pre-hospital management by the Emergency Medical Retrieval and Transfer Service and 30-day mortality was assessed using multivariable logistic regression. In total, data from 4035 patients were analysed, of which 412 (10%) were treated by the Emergency Medical Retrieval and Transfer Service. A greater proportion of patients treated by the Emergency Medical Retrieval and Transfer Service had an injury severity score ≥ 16 and Glasgow coma scale ≤ 12 (288 (70%) vs. 1435 (40%) and 126 (31%) vs. 325 (9%), respectively). The unadjusted 30-day mortality rate was 11.7% for patients managed by the Emergency Medical Retrieval and Transfer Service compared with 9.6% for patients managed by standard pre-hospital care services. However, after adjustment for differences in case-mix, the 30-day mortality rate for patients treated by the Emergency Medical Retrieval and Transfer Service was 37% lower (adjusted odds ratio 0.63 (95%CI 0.41-0.97); p = 0.037). The introduction of an emergency medical retrieval service was associated with a reduction in 30-day mortality for patients with blunt traumatic injury.
Assuntos
Cuidados Críticos , Serviços Médicos de Emergência/estatística & dados numéricos , Ferimentos e Lesões/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Médicos/psicologia , Sistema de Registros , Estudos Retrospectivos , Fatores de Tempo , País de Gales , Ferimentos e Lesões/mortalidade , Adulto JovemRESUMO
This study compared cows that consistently produce milk with small (volume-weighted mean diameter of 2.92-3.83 µm, with an average diameter of 3.29 µm) or large (volume-weighted mean diameter of 4.58-5.67 µm, with an average diameter of 4.92 µm) milk fat globule (MFG) size distributions in terms of the fatty acid (FA) composition of the MFG core. Selected cows fell into the respective size group over at least 3 independent measurements, including an observation period before the experiment. Further selection criteria were similar milk production traits between cows (milk yield, fat yield, fat/protein ratio) and established lactation (>50 d in milk). However, the selected groups differed in parity (parity 1-3 and 3-5 in the small and large MFG groups, respectively), and the small MFG group was an average of 25 d in milk later in their lactation period. All cows were under the same nutritional management and environmental conditions. Here, we show that cows with the small or large MFG phenotype differed in their lipid metabolism in terms of the FA composition of the MFG core. Our results indicate that cows with the small MFG phenotype produced milk with higher concentrations of unsaturated FA despite being fed the same diet. We suggest that this characteristic of the small MFG phenotype is the result of increased uptake of long-chain FA from the blood circulation. A relationship between the degree of unsaturation and MFG size was also identified in preliminary studies across other species-namely, camels, sheep, and goats. These findings show the potential for on-farm selection of cows (and potentially other dairy species) based on MFG size to produce milk with improved nutrient composition. This could lead to purpose-specific separation of milk based on MFG size and FA profile, both known to alter the technological properties of milk.
Assuntos
Bovinos/fisiologia , Ácidos Graxos/metabolismo , Glicolipídeos/metabolismo , Glicoproteínas/metabolismo , Metabolismo dos Lipídeos , Leite/química , Animais , Ácidos Graxos Insaturados/metabolismo , Feminino , Lactação , Gotículas Lipídicas , Leite/metabolismo , Nutrientes , FenótipoRESUMO
INTRODUCTION: Airborne fine particulate matter (PM2.5; particulate matter ≤ 2.5 µm in aerodynamic diameter) plays a key role in air quality, climate, and public health. Globally, the largest mass fraction of PM2.5 is organic, dominated by secondary organic aerosol (SOA) formed from atmospheric oxidation of volatile organic compounds (VOCs). Isoprene from vegetation is the most abundant nonmethane VOC emitted into Earth's atmosphere. Isoprene has been recently recognized as one of the major sources of global SOA production that is enhanced by the presence of anthropogenic pollutants, such as acidic sulfate derived from sulfur dioxide (SO2), through multiphase chemistry of its oxidation products. Considering the abundance of isoprene-derived SOA in the atmosphere, understanding mechanisms of adverse health effects through inhalation exposure is critical to mitigating its potential impact on public health. Although previous studies have examined the toxicological effects of certain isoprene-derived gas-phase oxidation products, to date, no systematic studies have examined the potential toxicological effects of isoprene-derived SOA, its constituents, or its SOA precursors on human lung cells. SPECIFIC AIMS: The overall objective of this study was to investigate the early biological effects of isoprene-derived SOA and its subtypes on BEAS-2B cells (a human bronchial epithelial cell line), with a particular focus on the alteration of oxidative stress- and inflammation-related genes. To achieve this objective, there were two specific aims.1. Examine toxicity and early biological effects of SOA derived from the photochemical oxidation of isoprene, considering both urban and downwind-urban types of chemistry.2. Examine toxicity and early biological effects of SOA derived directly from downstream oxidation products of isoprene (i.e., epoxides and hydroperoxides). METHODS: Isoprene-derived SOA was first generated by photooxidation of isoprene under natural sunlight in the presence of nitric oxide (NO) and acidified sulfate aerosols. Experiments were conducted in a 120-m3 outdoor Teflon-film chamber located on the roof of the Gillings School of Global Public Health, University of North Carolina at Chapel Hill (UNC-Chapel Hill). BEAS-2B cells were exposed to chamber- generated isoprene-derived SOA using the Electrostatic Aerosol in Vitro Exposure System (EAVES). This approach allowed us to generate atmospherically relevant compositions of isoprene-derived SOA and to examine its toxicity through in vitro exposures at an air-liquid interface, providing a more biologically relevant exposure model. Isoprene-derived SOA samples were also collected, concurrently with EAVES sampling, onto Teflon membrane filters for in vitro resuspension exposures and for analysis of aerosol chemical composition by gas chromatography/electron ionization-quadrupole mass spectrometry (GC/EI-MS) with prior trimethylsilylation and ultra-performance liquid-chromatography coupled to high-resolution quadrupole time-of-flight mass spectrometry equipped with electrospray ionization (UPLC/ESI-HR-QTOFMS). Isoprene-derived SOA samples were also analyzed by the dithiothreitol (DTT) assay in order to characterize their reactive oxygen species (ROS)-generation potential.Organic synthesis of known isoprene-derived SOA precursors, which included isoprene epoxydiols (IEPOX), methacrylic acid epoxide (MAE), and isoprene-derived hydroxyhydroperoxides (ISOPOOH), was conducted in order to isolate major isoprene-derived SOA formation pathways from each other and to determine which of these pathways (or SOA types) is potentially more toxic. Since IEPOX and MAE produce SOA through multiphase chemistry onto acidic sulfate aerosol, dark reactive uptake experiments of IEPOX and MAE in the presence of acidic sulfate aerosol were performed in a 10-m3 flexible Teflon indoor chamber at UNC-Chapel Hill. Since the generation of SOA from ISOPOOH (through a non-IEPOX route) requires a hydroxyl radical (â¢OH)-initiated oxidation, ozonolysis of tetramethylethylene (TME) was used to form the needed â¢OH radicals in the indoor chamber. The resultant low-volatility multifunctional hydroperoxides condensed onto nonacidified sulfate aerosol, yielding the ISOPOOH-derived SOA needed for exposures. Similar to the outdoor chamber SOAs, IEPOX, MAE- and ISOPOOH-derived SOAs were collected onto Teflon membrane filters and were subsequently chemically characterized by GC/EI-MS and UPLC/ESI-HR-QTOFMS as well as for ROS-generation potential using the DTT assay. These filters were also used for resuspension in vitro exposures.By conducting gene expression profiling, we provided mechanistic insights into the potential health effects of isoprene-derived SOA. First, gene expression profiling of 84 oxidative stress- and 249 inflammation-associated human genes was performed for cells exposed to isoprene-derived SOA generated in our outdoor chamber experiments in EAVES or by resuspension. Two pathway-focused panels were utilized for this purpose: (1) nCounter GX Human Inflammation Kit comprised of 249 human genes (NanoString), and (2) Human Oxidative Stress Plus RT2 Profiler PCR Array (Qiagen) comprised of 84 oxidative stress-associated genes. We compared the gene expression levels in cells exposed to SOA generated in an outdoor chamber from photochemical oxidation of isoprene in the presence of NO and acidified sulfate seed aerosol to cells exposed to a dark control mixture of isoprene, NO, and acidified sulfate seed aerosol to isolate the effects of the isoprene-derived SOA on the cells using the EAVES and resuspension exposure methods. Pathway-based analysis was performed for significantly altered genes using the ConsensusPathDB database, which is a database system for the integration of human gene functional interactions to provide biological pathway information for a gene set of interest. Pathway annotation was performed to provide biological pathway information for each gene set. The gene-gene interaction networks were constructed and visualized using the GeneMANIA Cytoscape app (version 3.4.1) to predict the putative function of altered genes. Lastly, isoprene-derived SOA collected onto filters was used in resuspension exposures to measure select inflammatory biomarkers, including interleukin 8 (IL-8) and prostaglandin-endoperoxide synthase 2 (PTGS2) genes, in BEAS-2B cells to ensure that effects observed from EAVES exposures were attributable to particle-phase organic products. Since EAVES and resuspension exposures compared well, gene expression profiling for IEPOX-, MAE- and ISOPOOH-derived SOA were conducted using only resuspension exposures. RESULTS AND CONCLUSIONS: Chemical characterization coupled with biological analyses show that atmospherically relevant compositions of isoprene-derived SOA alter the levels of 41 oxidative stress-related genes. Of the different composition types of isoprene-derived SOA, MAE- and ISOPOOH-derived SOA altered the greatest number of genes, suggesting that carbonyl and hydroperoxide functional groups are oxidative stress promoters. Taken together, the different composition types accounted for 34 of the genes altered by the total isoprene-derived SOA mixture, while 7 remained unique to the total mixture exposures, indicating that there is either a synergistic effect of the different isoprene-derived SOA components or an unaccounted component in the mixture.The high-oxides of nitrogen (NOx) regime, which yielded MAE- and methacrolein (MACR)-derived SOA, had a higher ROS-generation potential (as measured by the DTT assay) than the low- NOx regime, which included IEPOX- and isoprene-derived SOA. However, ISOPOOH-derived SOA, which also formed in the low- NOx regime, had the highest ROS-generation potential, similar to 1,4-naphthoquinone (1,4-NQ). This suggests that aerosol-phase organic peroxides contribute significantly to particulate matter (PM) oxidative potential. MAE- and MACR- derived SOA showed equal or greater ROS-generation potential than was reported in prior UNC-Chapel Hill studies on diesel exhaust PM, highlighting the importance of a comprehensive investigation of the toxicity of isoprene-derived SOA. Notably, ISOPOOH-derived SOA was one order of magnitude higher in ROS-generation potential than diesel exhaust particles previously examined at UNC-Chapel Hill. As an acellular assay, the DTT assay may not be predictive of oxidative stress; therefore, we also focused on the gene expression results from the cellular exposures.We have demonstrated that the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and the redox-sensitive activation protein-1 (AP-1) transcription factor networks have been significantly altered upon exposure to isoprene-derived SOA. The identification of Nrf2 pathway in cells exposed to isoprene-derived SOA is in accordance with our findings using the DTT assay, which measures the thiol reactivity of PM samples as a surrogate for their ROS-generation potential. Specifically, our results point to the cysteine-thiol modifications within cells that lead to activation of Nrf2-related gene expression.However, based on our gene expression results showing no clear relationship between DTT activity and the number of altered oxidative stress-related genes, the DTT activity of isoprene-derived SOA may not be directly indicative of toxicity relative to other SOA types. While activation of Nrf2-associated genes has been identified with responses to oxidative stress and linked to traffic related air pollution exposure in both toxicological and epidemiological studies, their implicit involvement in this study suggests that activation of Nrf2-related gene expression may occur with exposures to all sorts of PM types.By controlling the exposure time, method, and dose we demonstrated that among the SOA derived from previously identified individual precursors of isoprene-derived SOA, ISOPOOH-derived SOA alters moreoxidative stress related genes than does IEPOX-derived SOA, but fewer than MAE-derived SOA. This suggests that the composition of MAE-derived SOA may be the greatest contributor to alterations of oxidative stress-related gene expression observed due to isoprene-derived SOA exposure. Further study on induced levels of protein expression and specific toxicological endpoints is necessary to determine if the observed gene expression changes lead to adverse health effects. In addition, such studies have implications for pollution-control strategies because NOx and SO2 are controllable pollutants that can alter the composition of SOA, and in turn alter its effects on gene expression. The mass fraction of different components of atmospheric isoprene derived SOA should be considered, but altering the fraction of high- NOx isoprene-derived SOA (e.g., MAE derived SOA) may yield greater changes in gene expression than altering the fraction of low- NOx isoprene derived SOA types (ISOPOOH- or IEPOX-derived SOA). Finally, this study confirms that total isoprene-derived SOA alters the expression of a greater number of genes than does SOA derived from the tested precursors. This warrants further work to determine the underlying explanation for this observation, which may be uncharacterized components of isoprene-derived SOA or the potential for synergism between the studied components.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Butadienos/metabolismo , Hemiterpenos/metabolismo , Oxidantes Fotoquímicos/metabolismo , Material Particulado/metabolismo , Expressão Gênica/efeitos dos fármacos , HumanosAssuntos
Ciências do Comportamento , Política Pública , Humanos , Política de Saúde , Organizações , Saúde PúblicaRESUMO
INTRODUCTION: Workers in aluminium production are exposed to a complex mixture of particles and gases potentially harmful to the airways, among them aluminium oxide (Al2O3). With the use of an exposure chamber, we aimed to examine the effects of short-term controlled exposure to Al2O3 on lung function and inflammatory markers in healthy volunteers. METHODS: 15 men (age 19-31) were exposed in random order to clean air or Al2O3 particles (3.8-4.0â mg/m(3)) for 2â h including 30â min exercise (stationary bike, 75â W). The permissible exposure level (PEL) for Al2O3 by Occupational Safety and Health Administration, USA, is 5â mg/m(3) time weighted average (TWA). Sham and particle exposures were separated by at least 2 weeks. Spirometry was carried out, and induced sputum and blood samples were collected 48â h before and 4 and 24â h after exposure. RESULTS: Levels of sputum neutrophils (mean (±SEM)) was increased 24â h post-Al2O3 vs pre-Al2O3 exposure (43% (4) vs 31% (4), p=0.01) and the protein level of interleukin (IL)-8 had a 4.8 (0.9)-fold change increase 24â h after exposure (p<0.01). Following Al2O3 exposure, gene signatures in sputum were significantly increased related to several pathways. CONCLUSIONS: The present study suggests that controlled exposure to Al2O3 particles at levels below PEL (TWA) induces airway inflammation in healthy humans marked by elevated neutrophils and elevated IL-8. In addition, increased expression of genes associated with several biological processes was observed in sputum. Interestingly, inhaled Al2O3-induced effects were localised to the airways and not systemic.
Assuntos
Óxido de Alumínio/efeitos adversos , Inflamação/etiologia , Exposição por Inalação/efeitos adversos , Interleucina-8/metabolismo , Pulmão/efeitos dos fármacos , Neutrófilos/metabolismo , Escarro/metabolismo , Adulto , Biomarcadores/metabolismo , Expressão Gênica , Voluntários Saudáveis , Humanos , Inflamação/genética , Inflamação/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Masculino , Exposição Ocupacional/efeitos adversos , Espirometria , Adulto JovemRESUMO
Emergency tracheal intubation undertaken by Rapid sequence induction (RSI) is a fundamental component of military anaesthesia. This common emergency procedure has evolved in both civilian and military practice, since it was first described, as new drugs have become available. Current practice now differs significantly from that undertaken by the procedure's initial advocates. This is particularly the case in the deployed military environment. As military medicine continues to improve injury survivability, RSI will be undertaken in increasingly unstable casualties, requiring a bespoke emergency induction not commonly practised in the civilian setting.
Assuntos
Anestesia/métodos , Anestésicos Intravenosos/uso terapêutico , Intubação Intratraqueal/métodos , Fármacos Neuromusculares Despolarizantes/uso terapêutico , Succinilcolina/uso terapêutico , Tiopental/uso terapêutico , Humanos , Intubação Gastrointestinal/métodos , Oxigenoterapia/métodos , Posicionamento do Paciente/métodosRESUMO
Thirty-six Angus and Angus×Simmental heifers, averaging 291 kg, were used to determine the effects of dietary Cr, in the form of Cr propionate (Cr Prop), on glucose metabolism and serum insulin concentrations following glucose administration. Heifers were stratified by body weight (BW) within a breed and randomly assigned to treatments. Treatments consisted of 0, 3, 6, or 9 mg of supplemental Cr/d from Cr Prop. Based on dry matter (DM) intakes, the daily doses of Cr were equivalent to 0.47, 0.94, and 1.42 mg of supplemental Cr/kg of DM. Heifers were individually fed a corn silage-based diet at a level of 2% of BW. Each heifer was also fed 0.45 kg of a ground corn supplement daily that served as a carrier for supplemental Cr. Glucose tolerance tests were performed on d 44 of the study. Glucose was infused via jugular catheters at a level of 0.45 g/kg of BW(0.75) over a course of 1 to 2 min. Blood samples were collected at -10, 0, 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180 min relative to glucose dosing for glucose and insulin determination. Area under the glucose response curve was lower (1,603 vs. 1,964 mg/dL per minute) in heifers supplemented with Cr from 0 to 45 min following glucose challenge. Serum insulin concentrations were lower in Cr-supplemented heifers than in controls following glucose infusion. The molar ratio of insulin to glucose was also lower in Cr-supplemented heifers relative to controls. Serum insulin and serum insulin to glucose ratios did not differ among heifers supplemented with 3, 6, or 9 mg of Cr/d. Results indicate that Cr Prop supplementation increased tissue sensitivity to insulin in growing heifers. Based on insulin sensitivity, Cr requirements (as Cr Prop) of growing heifers can be met by supplementing with 3 mg of Cr/d or 0.47 mg of Cr/kg of DM.
Assuntos
Bovinos/crescimento & desenvolvimento , Dieta/veterinária , Insulina/sangue , Propionatos/administração & dosagem , Animais , Glicemia/análise , Suplementos Nutricionais , Ácidos Graxos não Esterificados/sangue , Feminino , Glucose/administração & dosagem , Teste de Tolerância a Glucose , Zea maysRESUMO
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) frequently results from synergism between chemical and infectious liver carcinogens. Worldwide, the highest incidence of HCC is in regions endemic for the foodborne contaminant aflatoxin B1 (AFB1) and hepatitis B virus (HBV) infection. Recently, gut microbes have been implicated in multisystemic diseases including obesity and diabetes. Here, the hypothesis that specific intestinal bacteria promote liver cancer was tested in chemical and viral transgenic mouse models. METHODS: Helicobacter-free C3H/HeN mice were inoculated with AFB1 and/or Helicobacter hepaticus. The incidence, multiplicity and surface area of liver tumours were quantitated at 40 weeks. Molecular pathways involved in tumourigenesis were analysed by microarray, quantitative real-time PCR, liquid chromatography/mass spectrometry, ELISA, western blot and immunohistochemistry. In a separate experiment, C57BL/6 FL-N/35 mice harbouring a full-length hepatitis C virus (HCV) transgene were crossed with C3H/HeN mice and cancer rates compared between offspring with and without H hepaticus. RESULTS: Intestinal colonisation by H hepaticus was sufficient to promote aflatoxin- and HCV transgene-induced HCC. Neither bacterial translocation to the liver nor induction of hepatitis was necessary. From its preferred niche in the intestinal mucus layer, H hepaticus activated nuclear factor-kappaB (NF-kappaB)-regulated networks associated with innate and T helper 1 (Th1)-type adaptive immunity both in the lower bowel and liver. Biomarkers indicative of tumour progression included hepatocyte turnover, Wnt/beta-catenin activation and oxidative injury with decreased phagocytic clearance of damaged cells. CONCLUSIONS: Enteric microbiota define HCC risk in mice exposed to carcinogenic chemicals or hepatitis virus transgenes. These results have implications for human liver cancer risk assessment and prevention.
Assuntos
Aflatoxina B1/toxicidade , Hepatite B/complicações , Intestinos/microbiologia , Neoplasias Hepáticas Experimentais/etiologia , Imunidade Adaptativa , Animais , Proliferação de Células , Transformação Celular Neoplásica/genética , Quimiocinas/sangue , Cocarcinogênese , Feminino , Infecções por Helicobacter/complicações , Helicobacter hepaticus , Hepatite B/imunologia , Imunidade Inata , Subunidade p40 da Interleucina-12/sangue , Neoplasias Hepáticas Experimentais/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Estresse Oxidativo/fisiologia , Fatores Sexuais , Transdução de Sinais/fisiologia , Células Th1/imunologiaRESUMO
Eight primiparous and 8 multiparous Holstein cows were used to determine the effects of Cr supplementation, in the form of Cr propionate (Cr Prop), on milk and tissue Cr concentrations. Cows were randomly assigned by parity to one of 2 diets: 1) control diet or 2) 2 mg of supplemental Cr/kg of DM. The level of Cr Prop supplemented exceeded by 4-fold the concentration of 0.5 mg of Cr/kg permitted by the FDA. Experimental diets were fed from approximately 30 d prepartum until at least 91 d postpartum, resulting in a minimum of 121 d of exposure to supplemental Cr. The control prepartum and postpartum diets analyzed 0.48 and 0.38 mg of Cr/kg of DM, respectively. Milk samples were obtained from the a.m. milking on d 0 (colostrum), 7, 14, 21, 28, 42, 56, 77, and 90 and on the final day of the study for Cr analysis. Cows were harvested after lactating for a minimum of 91 d and samples of liver, kidney, semitendinosus muscle, and fat were obtained for Cr analysis. Chromium was measured using electrothermal atomic absorption spectrophotometry. Milk Cr concentration averaged 1.7 ng/mL and was affected by day of lactation but not by Cr or a Cr × day interaction. Supplementation of 2 mg of Cr/kg of DM increased kidney Cr by approximately 3-fold and liver Cr concentrations by approximately 2-fold. Chromium concentrations in muscle and fat were not affected by Cr supplementation. In summary, supplementation of Cr Prop at a level of 2 mg of Cr/kg of DM did not affect Cr concentration in milk, muscle, or fat, the major bovine products consumed by humans.
Assuntos
Bovinos/metabolismo , Suplementos Nutricionais , Leite/química , Propionatos/administração & dosagem , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , FemininoRESUMO
A 56-d experiment was designed to examine the effect of high dietary Fe on metal transporters involved in Fe and Mn metabolism. Fourteen weaned Holstein calves were stratified by weight and randomly assigned to 1 of 2 treatments: 1) no supplemental Fe (normal Fe) or 2) 750mg of supplemental Fe/kg of dry matter (high Fe). Jugular blood was collected on d 0, 35, and 56. At the end of the trial, 6 calves per treatment were humanely killed and duodenal scrapings, liver, and heart were collected for analysis. Additionally, proximal duodenum was mounted on Ussing chambers to assess intestinal barrier integrity. Calves receiving high dietary Fe displayed decreased transepithelial resistance and increased apical-to-basolateral flux of radiolabeled mannitol, suggesting that high Fe created increased intestinal permeability. Feeding calves a diet high in Fe decreased average daily gain, dry matter intake, and feed efficiency. Hemoglobin and serum Fe concentrations did not differ due to dietary treatment. High dietary Fe increased concentrations of Fe in the liver, but did not affect heart or duodenal Fe concentrations. Duodenal Mn concentrations were lowered by feeding a high Fe diet, but liver and heart Mn concentrations were not affected. As determined by real-time reverse transcription PCR, relative hepatic expression of the gene that encodes the Fe regulatory hormone hepcidin was 5-fold greater in calves fed high dietary Fe. Hepcidin is released in response to increased Fe status and binds to the Fe export protein ferroportin causing ferroportin to be degraded, thereby reducing dietary Fe absorption. Confirmation of this result was achieved through Western blotting of duodenal protein, which revealed that ferroportin was decreased in calves fed high dietary Fe. Duodenal protein expression of divalent metal transporter 1 (DMT1), a Fe import protein that can also transport Mn, tended to be reduced by high dietary Fe. Transcript levels of several genes involved in Fe metabolism in liver and duodenum were unchanged by treatment. In summary, feeding calves a diet high in Fe induced a signal cascade (hepcidin) designed to reduce absorption of Fe (via reduced protein expression of ferroportin and DMT1) in a manner similar to that reported in rodents. Additionally, reduced levels of DMT1 protein appeared to decrease duodenal Mn, suggesting that Mn may also be a substrate for DMT1 in cattle.
Assuntos
Bovinos/fisiologia , Dieta/veterinária , Ferro da Dieta/metabolismo , Ferro/metabolismo , Manganês/metabolismo , Animais , Peso Corporal/fisiologia , Bovinos/metabolismo , Duodeno/química , Duodeno/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Coração/efeitos dos fármacos , Ferro/análise , Ferro/sangue , Ferro da Dieta/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Manganês/análise , Manganês/sangue , Proteínas de Membrana Transportadoras/metabolismo , Miocárdio/química , Estresse Oxidativo/efeitos dos fármacosRESUMO
Thirty-six Angus and Angus x Simmental cross steers (initial BW 269.5 +/- 22.3 kg) were used to determine the effects of dietary boron (B) on performance and immune function. Steers were fed on one of the three dietary treatments: (i) control (no supplemental B; 7.2 mg B/kg DM), (ii) 5 mg supplemental B/kg DM and (iii) 50 mg supplemental B/kg DM, from sodium borate for 78 days. Supplementation of dietary B had no effect on body weight (BW) gain, feed intake or gain:feed during the study. Jugular blood samples were collected prior to feeding on days 28, 63 and 77 for plasma-B analysis. Supplementation of dietary B increased (p < 0.001) plasma B-concentration in a dose-responsive manner. Furthermore, plasma B-concentration was correlated (p < 0.001; R(2) = 0. 95) to daily B-intake (mg B/day). Jugular blood was also collected, from an equal number of steers from each treatment, on day 42 or 44 for determination of in vitro production of interferon-gamma and tumour necrosis factor-alpha from isolated monocytes and assessment of lymphocyte proliferation. Dietary B did not affect T- or B-lymphocyte proliferation or in vitro cytokine production from monocytes. On day 49 of the study, the humoral immune response was assessed by i.m. injection of a 25% pig red blood cell (PRBC) solution for determination of anti-PRBC IgG and IgM titre responses. Boron-supplemented steers had greater (p = 0.035) anti-PRBC IgG titres than controls on day 7 but not on day 14 or 21 post-injection. Anti-PRBC IgM titres did not differ throughout the sampling period. Results from this study indicate that supplemental B had minimal effects on immune function and did not affect performance of growing steers.
Assuntos
Boro/farmacologia , Bovinos/crescimento & desenvolvimento , Bovinos/imunologia , Dieta/veterinária , Suplementos Nutricionais , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Boro/administração & dosagem , Boro/sangue , Relação Dose-Resposta a Droga , Masculino , Fito-Hemaglutininas/imunologia , Fatores de Tempo , Aumento de PesoRESUMO
An experiment was conducted to test the hypothesis that copper (Cu) hydroxychloride improves growth performance by upregulating the mRNA transcription of genes involved in lipid metabolism of pigs fed a diet based on corn, soybean meal (SBM), and distillers dried grains with solubles (DDGS). Thirty-two pigs (15.05 ± 0.98 kg) were allotted to 2 dietary treatments with 2 pigs per pen for a total of 8 replicate pens per treatment. Pigs were fed a corn-SBM-DDGS control diet that included Cu to meet the requirement. A second diet was formulated by adding 150 mg Cu/kg from copper hydroxychloride to the control diet. On the last day of the experiment, one pig per pen was sacrificed, and samples from liver, skeletal muscle, and subcutaneous adipose tissue were collected to analyze relative mRNA abundance of genes involved in lipid metabolism. Results indicated that overall ADG and G:F were greater (P < 0.05) for pigs fed the diet containing copper hydroxychloride compared with pigs fed the control diet. Pigs fed the diet supplemented with copper hydroxychloride also had increased (P < 0.05) abundance of cluster of differentiation 36 in the liver and increased (P < 0.05) abundance of fatty acid-binding protein 4 and lipoprotein lipase in subcutaneous adipose tissue. Inclusion of copper hydroxychloride also tended to increase (P < 0.10) the abundance of fatty acid-binding protein 1, peroxisome proliferator-activated receptor α, and carnitine palmitoyltransferase 1B in the liver, skeletal muscle, and subcutaneous adipose tissue, respectively. This indicates that dietary Cu may affect signaling pathways associated with lipid metabolism by improving the uptake, transport, and utilization of fatty acids. In conclusion, supplementation of copper hydroxychloride to the control diet improved growth performance and upregulated the abundance of some genes involved in postabsorptive metabolism of lipids.
Assuntos
Cobre/administração & dosagem , Suplementos Nutricionais/análise , Metabolismo dos Lipídeos/efeitos dos fármacos , Suínos/fisiologia , Ração Animal/análise , Animais , Dieta/veterinária , Feminino , Masculino , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/patologia , Glycine max , Suínos/genética , Suínos/crescimento & desenvolvimento , Zea maysRESUMO
An experiment was conducted to test the hypothesis that Cu hydroxychloride improves nutrient digestibility and alters the concentration of microbial protein in the small intestine or large intestine by pigs fed a corn-soybean meal diet or a diet based on corn, soybean meal, and distillers dried grains with solubles (DDGS). Twenty-four barrows (33.3 ± 3.4 kg) that had a T-cannula installed in the distal ileum were allotted to a 2 × 2 factorial design with 2 levels of DDGS (0% or 45%) and 2 levels of supplemental Cu from Cu hydroxychloride (0 or 150 mg/kg). A 2-period switch back design with the 4 diets and 6 replicate pigs per diet in each period was used resulting in 12 replicate pigs per diet for the 2 periods. The initial 9 d of each period was considered an adaptation period to the experimental diets. For each period, feces were collected on days 10, 11, and 12, and ileal digesta were collected for 8 h on days 13 and 14. Results indicated that inclusion of 45% DDGS to diets reduced (P < 0.05) the apparent ileal digestibility (AID) of AA and the AID and the apparent total tract digestibility (ATTD) of dry matter, gross energy, and crude protein. In contrast, inclusion of DDGS to diets increased (P < 0.05) the AID and the ATTD of acid hydrolyzed ether extract and the concentration of microbial protein in the hindgut (P < 0.05). However, the total concentration of volatile fatty acids (VFA) in ileal digesta and in feces from pigs fed the DDGS diets were not different from concentrations in pigs fed diets without DDGS. The AID and ATTD of dry matter, gross energy, and crude protein were not affected by dietary Cu concentrations, but the AID and ATTD of acid hydrolyzed ether extract were greater (P < 0.05) in diets supplemented with Cu hydroxychloride compared with diets without Cu hydroxychloride. There was also a reduction (P < 0.05) in the concentration of microbial protein and a tendency for a reduction (P < 0.10) in the total concentration of VFA in feces when diets were supplemented with Cu hydroxychloride. In conclusion, supplementation of Cu hydroxychloride to diets improved AID and ATTD of acid hydrolyzed ether extract and reduced the concentration of microbial protein in the large intestine and this effect was observed in diets containing DDGS as well as in diets without DDGS.
Assuntos
Ração Animal/análise , Cobre/farmacologia , Dieta/veterinária , Suínos/crescimento & desenvolvimento , Fenômenos Fisiológicos da Nutrição Animal , Animais , Cobre/química , Estudos Cross-Over , Suplementos Nutricionais , Digestão/efeitos dos fármacos , Íleo/fisiologia , Masculino , NutrientesRESUMO
We aimed to examine the case mix of adolescents presenting to an adult Emergency Department (ED) and to survey a representative sample regarding their perceived care. Of the 323 visits reviewed, 215 (66.6%) were males. Presentations increased at the weekend (151/323, 46.7%). Most visits were non-urgent, 34 (10.5%) were admitted. Acute injuries accounted for 156/215 (72.6%) of male presentations. 12/17 (70.5%) of those with a psychosocial presenting problem registered between 9 p.m. and 9 a.m. 33 adolescents presented during the prospective study period. 6 were excluded, 3 were lost to follow-up. 10/24 (41.7%) described the time they were waiting to be seen by a doctor as unacceptable, 9 (37.5%) wanted more privacy and 11 (45.9%) reported a delay in receiving treatment. Adolescents represent a minority in the ED, but have specific needs. We recommend the availability of age specific health promotion information and training of staff in adolescent healthcare issues.
Assuntos
Serviços de Saúde do Adolescente/normas , Serviço Hospitalar de Emergência/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Qualidade da Assistência à Saúde , Adolescente , Adulto , Fatores Etários , Continuidade da Assistência ao Paciente , Bases de Dados como Assunto , Grupos Diagnósticos Relacionados , Serviço Hospitalar de Emergência/normas , Feminino , Pesquisas sobre Atenção à Saúde , Hospitais Universitários , Humanos , Irlanda , Masculino , Estudos Prospectivos , Psicologia do AdolescenteRESUMO
Three experiments were conducted to determine effects of Cu hydroxychloride on DE and ME, apparent total tract digestibility (ATTD) of energy and acid hydrolyzed ether extract (AEE), and growth performance of pigs fed a diet based on corn and soybean meal (SBM). In Exp. 1, 80 weanling pigs (6.80 ± 1.69 kg) were allotted to 2 treatments with 4 pigs per pen and 10 pen replicates per diet. Pigs were fed a corn-SBM control diet that had Cu added to meet the requirement. A second diet was formulated by adding 150 mg Cu/kg from Cu hydroxychloride to the control diet. Both diets were fed for 4 wk. Results indicated that ADG, G:F, and final BW were greater ( ≤ 0.05) and fecal scores were reduced ( ≤ 0.05) for pigs fed the diet containing150 mg Cu/kg as hydroxychloride compared with pigs fed the control diet. In Exp. 2, 36 barrows (9.89 ± 1.21 kg) were randomly allotted to 3 dietary treatments and placed in metabolism crates. The control diet was based on corn and SBM and contained 20 mg Cu/kg. Two additional diets were formulated by adding 100 or 200 mg Cu/kg from Cu hydroxychloride to the control diet. Diets were fed for 28 d, with feces and urine being collected from d 9 to 14, d 16 to 21, and d 23 to 28. The DE and ME of diets and the ATTD of GE and AEE were not affected by dietary Cu concentrations, but increased ( < 0.01) by collection period. In Exp. 3, 150 pigs (10.22 ± 1.25 kg) were fed the same 3 diets as used in Exp. 2. Diets were provided on an ad libitum basis for 4 wk. Fecal scores were recorded, and on the last day of the experiment, blood samples were collected and tumor necrosis factor-α (TNF-α), IgA, blood urea N, total protein, and albumin were measured. Phase 1 ADG and G:F and final BW on d 28 were greater ( ≤ 0.05) for pigs fed diets containing 100 or 200 mg Cu/kg supplemented by Cu hydroxychloride compared with pigs fed the control diet. Pigs fed the diets supplemented with Cu hydroxychloride also had reduced ( ≤ 0.05) overall fecal scores and diarrhea frequency compared with pigs fed the control diet. However, no differences among treatments were observed for concentrations of TNF-α, IgA, blood urea N, total protein, or albumin. In conclusion, supplementation of Cu as Cu hydroxychloride to diets fed to weanling pigs improved growth performance and reduced diarrhea frequency, but this did not appear to be a result of increased digestibility of energy or AEE.
Assuntos
Cloretos/farmacologia , Cobre/farmacologia , Diarreia/veterinária , Suplementos Nutricionais , Doenças dos Suínos/tratamento farmacológico , Suínos/crescimento & desenvolvimento , Ração Animal/análise , Animais , Diarreia/tratamento farmacológico , Dieta/veterinária , Digestão/efeitos dos fármacos , Metabolismo Energético , Éter , Fezes , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Masculino , Distribuição Aleatória , Glycine max , Suínos/fisiologia , Zea maysRESUMO
Cadmium (Cd) is an environmental pollutant that has been associated with cardiovascular disease in populations, but the relationship of Cd with hypertension has been inconsistent. We studied the association between urinary Cd concentrations, a measure of total body burden, and blood pressure in American Indians, a US population with above national average Cd burden. Urinary Cd was measured using inductively coupled plasma mass spectrometry, and adjusted for urinary creatinine concentration. Among 3714 middle-aged American Indian participants of the Strong Heart Study (mean age 56 years, 41% male, 67% ever-smokers, 23% taking antihypertensive medications), urinary Cd ranged from 0.01 to 78.48 µg g-1 creatinine (geometric mean=0.94 µg g-1) and it was correlated with smoking pack-year among ever-smokers (r2=0.16, P<0.0001). Participants who were smokers were on average light-smokers (mean 10.8 pack-years), and urinary Cd was similarly elevated in light- and never-smokers (geometric means of 0.88 µg g-1 creatinine for both categories). Log-transformed urinary Cd was significantly associated with higher systolic blood pressure in models adjusted for age, sex, geographic area, body mass index, smoking (ever vs never, and cumulative pack-years) and kidney function (mean blood pressure difference by lnCd concentration (ß)=1.64, P=0.002). These associations were present among light- and never-smokers (ß=2.03, P=0.002, n=2627), although not significant among never-smokers (ß=1.22, P=0.18, n=1260). Cd was also associated with diastolic blood pressure among light- and never-smokers (ß=0.94, P=0.004). These findings suggest that there is a relationship between Cd body burden and increased blood pressure in American Indians, a population with increased cardiovascular disease risk.