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1.
Osteoporos Int ; 32(7): 1379-1386, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33432459

RESUMO

When taken with a meal, α-glucosidase inhibitors (α-GI) reduce the rise in postprandial glucose and increase glucagon-like peptide-1 (GLP-1), and this may lower bone turnover. In this study, a salacinol-type α-GI increased GLP-1 and markedly reduced postprandial bone resorption compared to placebo, suggesting it could have implications for bone health. INTRODUCTION: Animal and clinical trials indicate that α-glucosidase inhibitors attenuate postprandial glycemic indices and increase secretion of GLP-1. In addition, GLP-1 acts on bone by inhibiting resorption. The goal in this study was to determine if a salacinol α-GI alters postprandial bone turnover and can be explained by changes in serum GLP-1. METHODS: In this double-blind, placebo-controlled crossover study, healthy overweight/obese adults (body mass index 29.0 ± 3.8 kg/m2; 21-59 years; n = 21) received a fixed breakfast and, in random order, were administered Salacia chinensis (SC; 500 mg) or placebo. A fasting blood sample was taken before and at regular intervals for 3 h after the meal. Serum was measured for bone turnover markers, C-terminal telopeptide of type I collagen (CTX) and osteocalcin, and for glycemic indices and gut peptides. RESULTS: Compared to placebo, SC attenuated the bone resorption marker, CTX, at 60, 90, and 120 min (p < 0.05) after the meal, and decreased osteocalcin, at 180 min (p < 0.05). As expected, SC attenuated the postprandial rise in glucose compared with placebo, whereas GLP-1 was increased at 60 min (p < 0.05) with SC. Serum GLP-1 explained 41% of the variance for change in postprandial CTX (p < 0.05). CONCLUSION: This study indicates that attenuating postprandial glycemic indices, with an α-GI, markedly decreases postprandial bone resorption and can be explained by the rise in GLP-1. Future studies should determine whether longer term α-GI use benefits bone health.


Assuntos
Reabsorção Óssea , Peptídeo 1 Semelhante ao Glucagon , Adulto , Animais , Glicemia , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/prevenção & controle , Estudos Cross-Over , Método Duplo-Cego , Inibidores de Glicosídeo Hidrolases , Humanos , Insulina , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico
2.
West Afr J Med ; 38(8): 770-774, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34503698

RESUMO

BACKGROUND: Plasmodium falciparum infection, like any other clinical condition, is prone to generating free radicals. This can worsen patients' clinical presentations. Antioxidants do help in ameliorating these free radical effects. These antioxidants, especially vitamins, are sometimes given routinely to patients with Plasmodium falciparum infection of which it can be given according to the severity of this free radical injury. METHODOLOGY: A total number of qualified 245 patients that came for malaria parasite test between March and October, 2020 were recruited into the study. Patients on arrival at the laboratory had their samples collected for malaria parasite test and for the proposed biochemical parameters (MDA, GPx, SOD and TAS). Malaria parasite test was used to categorize the severity of Plasmodium falciparum infection. RESULTS: There were statistically significant differences (p<0.0001) in MDA, GPx, SOD and TAS among patients with negative MP, 1+ and >2+ on blood film for malaria parasite. Patients with >2+ MP had highest levels (2.21±0.40) while patients with negative blood film had lowest levels(0.8194±0.33) of MDA. Patients with >2+ had lowest levels of GPx (2406.41±1272.10), SOD (104.54±30.62) and TAS (1.18±.35) as against patients with negative MP that had highest levels (5229.85±.2957.95)( 206.41±36.70)( 2.40±.53), respectively. CONCLUSION: There was evidence of free radical generation as evidenced with raised plasma malondialdehyde in patients with Plasmodium falciparum infection. This was associated with severity of this infection. There was also corresponding decrease in measured antioxidants (GPx, SOD and TAS).


CONTEXTE: L'infection à Plasmodium falciparum, comme toute autre affection clinique, est susceptible de générer des radicaux libres. Cela peut aggraver les présentations cliniques des patients. Les antioxydants aident à améliorer ces effets des radicaux libres. Ces antioxydants, notamment des vitamines, sont parfois administrés en routine aux patients infectés par Plasmodium falciparum dont il peut être administré en fonction de la gravité de cette lésion radicalaire. MÉTHODOLOGIE: Un nombre total de 245 patients qualifiés qui sont venus pour un test de dépistage du paludisme entre mars et octobre 2020 ont été recrutés dans l'étude. Les patients à leur arrivée au laboratoire ont eu leurs échantillons collectés pour le test du parasite du paludisme et pour les paramètres biochimiques proposés (MDA, GPx, SOD et TAS). Le test du parasite du paludisme a été utilisé pour catégoriser la gravité de l'infection à Plasmodium falciparum. RÉSULTATS: Il y avait des différences statistiquement significatives (p<0,0001) dans le MDA, GPx, SOD et TAS parmi les patients avec MP négatif, 1+ et >2+ sur frottis sanguin pour le parasite du paludisme. Les patients avec >2+ MP avaient les niveaux les plus élevés (2,21 ± 0,40) tandis que les patients avec un frottis sanguin négatif avaient les niveaux les plus bas (0,8194 ± 0,33) de MDA. Les patients avec >2+ avaient les niveaux les plus bas de GPx (2406,41 ± 1272,10), SOD (104,54 ± 30,62) et TAS (1,18 ± 0,35) par rapport aux patients avec MP négatif qui avaient les niveaux les plus bas (5229,85 ± 0,2957,95) (206,41 ± 36,70 )( 2,40 ± 0,53), respectivement. CONCLUSION: Il y avait des preuves de génération de radicaux libres comme en témoigne l'augmentation du malondialdéhyde plasmatique chez les patients infectés par Plasmodium falciparum. Ceci était associé à la gravité de cette infection. Il y avait également une diminution correspondante des antioxydants mesurés (GPx, SOD et TAS). Mots-clés: Radicaux libres, stress oxydatif, antioxydants, Plasmodium falciparum, paludisme.


Assuntos
Antioxidantes , Malária Falciparum , Radicais Livres , Humanos , Malondialdeído , Plasmodium falciparum
3.
J Dairy Sci ; 102(3): 2283-2297, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30660422

RESUMO

Postpartum dietary supplementation of gluconeogenic precursors may improve the plasma metabolite profile of dairy cows, reducing metabolic disorders and improving lactation performance. The objective of this trial was to examine the effects of supplementation with fermented ammoniated condensed whey (FACW) postpartum on lactation performance and on profile of plasma metabolites and hormones in transition dairy cows. Individually fed multiparous Holstein cows were blocked by calving date and randomly assigned to control (2.9% dry matter of diet as soybean meal; n = 20) or FACW (2.9% dry matter of diet as liquid GlucoBoost, Fermented Nutrition, Luxemburg, WI; n = 19) dietary treatments. Treatments were offered from 1 to 45 d in milk (DIM). Cows were milked twice a day. Dry matter intake and milk yield were recorded daily and averaged weekly. Individual milk samples from 2 consecutive milkings were obtained once a week for component analysis. Rumen fluid was collected (n = 3 cows/treatment) at 4 time points per day at 7 and 21 DIM. Blood samples were collected within 1 h before feeding time for metabolite analysis and hyperketonemia diagnosis. Supplementation of FACW improved feed efficiency relative to control; this effect may be partially explained by a marginally significant reduction in dry matter intake from wk 3 to 7 for FACW-supplemented cows with no detected FACW-driven changes in milk yield, milk protein yield, and milk energy output compared with control. Also, there was no evidence for differences in intake of net energy for lactation, efficiency of energy use, energy balance, or body weight or body condition score change from calving to 45 DIM between treatments. Supplementation of FACW shifted rumen measures toward greater molar proportions of propionate and butyrate, and lesser molar proportions of acetate and valerate. Cows supplemented with FACW had greater plasma glucose concentrations in the period from 3 to 7 DIM and greater plasma insulin concentrations compared with control. Plasma nonesterified fatty acid and ß-hydroxybutyrate concentrations were decreased in cows supplemented with FACW compared with control cows in the period from 3 to 7 DIM. These findings indicate that FACW may have improved the plasma metabolite profile immediately postpartum in dairy cows. Additionally, supplementation of FACW resulted in improved feed efficiency as accessed by measures of milk output relative to feed intake.


Assuntos
Compostos de Amônio/metabolismo , Bovinos/fisiologia , Hormônios/sangue , Período Pós-Parto/fisiologia , Soro do Leite/metabolismo , Ração Animal/análise , Animais , Análise Química do Sangue/veterinária , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Fermentação , Período Pós-Parto/efeitos dos fármacos , Soro do Leite/administração & dosagem
4.
Niger J Clin Pract ; 20(12): 1618-1621, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29378996

RESUMO

BACKGROUND: Stroke has been a global burden, with increasing morbidity and mortality. Serum cardiac troponin t (cTnT) and creatine kinase (CK-MB) fraction are reported to be elevated in patients admitted with acute ischaemic stroke and high level of these biomarkers indicated more severe stroke and neurologic deficit in some of the patients. OBJECTIVE: To evaluate the serum levels cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) in patients with acute ischaemic stroke and relate the analytes to severity of stroke. METHOD: Patients with clinical diagnosis of ischaemic stroke diagnosed, confirmed by brain Computerized Tomography scan and equal number of apparently healthy age and sex-matched were recruited. Serum cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) were analysed using ELISA method and Stroke severity was determined using National Institute of Health Stroke Score (NIHSS). RESULTS: Mean serum cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) in stroke patients were found to be higher than age sex matched control (p<0.05). NIHS Score of 12.2 ± 5.43 and 9.78 ± 3.97 were observed in Patients with elevated and normal cTnT respectively (p=0.009) while NIHS Score were similar in patients with elevated and normal CK-MB (p = 0.772). CONCLUSION: The mean values of serum cTnT and CK-MB were higher in acute ischaemic stroke patients compared to controls. Serum cardiac Troponin t level may be a significant biomarker of the severity of stroke.


Assuntos
Isquemia Encefálica/sangue , Creatina Quinase Forma MB/sangue , Acidente Vascular Cerebral/sangue , Troponina T/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Creatina Quinase/sangue , Creatina Quinase Forma MB/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Isoenzimas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Nigéria , Troponina T/metabolismo
5.
Clin Exp Rheumatol ; 33(6): 788-94, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26575830

RESUMO

OBJECTIVES: This paper aims to identify clinical and serological differences, damage accrual and mortality, in juvenile, adult and late-onset SLE. METHODS: We conducted our study with patients fulfilling SLE classification criteria taken from the Hospital Gregorio Marañon Autoimmune Systemic Rheumatic Diseases' Registry (1986 to 2012). Clinical characteristics, laboratory data and therapies used during the course of the disease were analysed with patients divided into 3 groups: juvenile-onset (≤ 18 years), adult-onset (19-50) and late onset (>50 years). RESULTS: Four hundred and forty-five patients were included. Renal disease and cutaneous manifestations were more frequent in the juvenile-onset group at disease onset. During follow-up, juvenile-onset group presented a higher incidence of renal disease, malar rash, Raynaud's phenomenon, cutaneous vasculitis, and neuropsychiatric manifestations than the other two groups. Arthritis and lymphopoenia were more frequent in the adult-onset group. Arterial hypertension and neoplasm were more frequent in the late-onset group. Low serum complement, anti-dsDNA, anti-U1RNP and anti-Sm antibodies were more common in the juvenile-onset group. Patients with late-onset SLE had more damage accrual. Thirty-seven patients (8.3%) died during the study. All-cause mortality was significantly higher in the late-onset group. Age at disease onset >50 years was an independent risk factor for damage accrual (OR, 2.2; 95%CI, 1.1-4.6; p=0.029) and mortality (OR, 2.6; 95%CI, 1.1-6.3; p=0.03). CONCLUSIONS: We found significant differences in clinical and serological profiles between juvenile, adult and late-onset SLE. The most significant of which was a higher prevalence of neuropsychiatric and renal complications as well as different autoantibody signatures for the juvenile-onset group.


Assuntos
Autoanticorpos , Hipertensão , Lúpus Eritematoso Sistêmico , Neoplasias , Adulto , Distribuição por Idade , Idade de Início , Idoso , Autoanticorpos/sangue , Autoanticorpos/classificação , Criança , Feminino , Seguimentos , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Monitorização Imunológica/métodos , Neoplasias/epidemiologia , Neoplasias/etiologia , Prevalência , Fatores de Risco , Espanha/epidemiologia , Análise de Sobrevida
6.
J Dairy Sci ; 98(9): 6535-51, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26210274

RESUMO

Genetic improvement of feed efficiency (FE) in dairy cattle requires greater attention given increasingly important resource constraint issues. A widely accepted yet occasionally contested measure of FE in dairy cattle is residual feed intake (RFI). The use of RFI is limiting for several reasons, including interpretation, differences in recording frequencies between the various component traits that define RFI, and potential differences in genetic versus nongenetic relationships between dry matter intake (DMI) and FE component traits. Hence, analyses focusing on DMI as the response are often preferred. We propose an alternative multiple-trait (MT) modeling strategy that exploits the Cholesky decomposition to provide a potentially more robust measure of FE. We demonstrate that our proposed FE measure is identical to RFI provided that genetic and nongenetic relationships between DMI and component traits of FE are identical. We assessed both approaches (MT and RFI) by simulation as well as by application to 26,383 weekly records from 50 to 200 d in milk on 2,470 cows from a dairy FE consortium study involving 7 institutions. Although the proposed MT model fared better than the RFI model when simulated genetic and nongenetic associations between DMI and FE component traits were substantially different from each other, no meaningful differences were found in predictive performance between the 2 models when applied to the consortium data.


Assuntos
Ração Animal , Dieta/veterinária , Modelos Genéticos , Animais , Bovinos , Ingestão de Energia , Feminino , Fenótipo , Reprodutibilidade dos Testes
7.
Int J Obes (Lond) ; 37(2): 272-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22310470

RESUMO

OBJECTIVE: One developing strategy for obesity treatment has been to use combinations of differently acting pharmacotherapies to improve weight loss with fewer adverse effects. The purpose of this study was to determine whether the combination of naltrexone (Nal), an opioid antagonist acting on the reward system, and exendin-4 (Ex-4), a glucagon-like peptide 1 agonist acting on satiety signaling, would produce larger reductions in food intake than either alone in rats. Because the anorectic potencies of both compounds have been associated with nausea and malaise, the influence of these drug combinations on the acquisition of a conditioned taste aversion (CTA) was also determined. METHODS: In Experiment 1, the acute anorectic effects of Nal (0.32-3.2 mg kg(-1); intraperitoneally (i.p.)) and Ex-4 (1-10 µg kg(-1); i.p.) were assessed alone or in combination. Combinational doses were further investigated by the repeated daily administration of 1 mg kg(-1) Nal+3.2 µg kg(-1) Ex-4 for 4 days. In Experiment 2, both compounds alone or in combination were used as unconditioned stimuli in a series of CTA tests. RESULTS: Nal and Ex-4, alone or in combination, suppressed food intake in a dose-dependent manner, and the interaction on food intake between Nal and Ex-4 was additive. In the CTA paradigm, Nal (1 mg kg(-1)) alone did not support acquisition, whereas a CTA was evident with doses of Ex-4 (1 or 3.2 µg kg(-1)). Combinations of Nal and Ex-4 also resulted in a more rapid and robust acquisition of a CTA. CONCLUSION: Given that the Nal and Ex-4 combination produces additive effects on not only food intake reduction but also food aversion learning, this specific drug combination does not have the benefit of minimizing the adverse effects associated with each individual drug. These data suggest that it is necessary to evaluate both the positive and adverse effects at early stages of combinational drug development.


Assuntos
Depressores do Apetite/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Naltrexona/farmacologia , Obesidade/tratamento farmacológico , Peptídeos/farmacologia , Peçonhas/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Interações Medicamentosas , Quimioterapia Combinada , Exenatida , Masculino , Obesidade/prevenção & controle , Ratos , Ratos Sprague-Dawley , Paladar/efeitos dos fármacos , Redução de Peso/efeitos dos fármacos
8.
J Dairy Sci ; 96(4): 2314-2326, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23462172

RESUMO

The objectives of this study were to investigate heterogeneity in the variance of and the association between milk yield (MY) and pregnancy outcome (PO) in dairy cows, formally separating the within-herd (i.e., cow-level residual effects) from the between-herd (i.e., herd-level random effects) components. Based on a recently developed extension to bivariate generalized hierarchical linear mixed models, we specified functions of residual and random effect variances and covariances as linear combinations of fixed and random effects to infer upon heterogeneity in the variation of and the association between MY and PO at first postpartum insemination. As potential sources of heterogeneity, we evaluated various management practices and herd attributes of interest by assessing model fit using the deviance information criterion. Our data consisted of 89,105 Dairy Herd Improvement Association cow records from 379 dairy herds in Michigan. Within herds, no evidence of a cow-level (residual) association between MY and PO was observed, as the corresponding association parameter did not significantly depart from zero. However, the herd-level (random effects) relationship between MY and PO was antagonistic and depended on management practices that determine the baseline level of fertility for a herd. In other words, herds with greater average MY at the time of first postpartum insemination had lower pregnancy rates, but within such herds, cows with higher daily yields did not seem to be any more or less likely to become pregnant than lower-yielding herdmates. Nevertheless, Michigan counties differed in the magnitude of the herd-level association between MY and PO, thus indicating that regional environmental conditions or management practices may partially alleviate the herd-level antagonism between MY and PO. The heterogeneity in variability of MY was substantial and primarily explained at the cow level by management conditions and other herd-specific attributes. In summary, the nature of the variability of and the association between MY and PO in dairy cows is complex due to the heterogeneous contributions of both cow- and herd-level components. Further research should be pursued to investigate additional management scenarios that ameliorate or even enhance the association between MY and PO in commercial dairy cows during first postpartum insemination.


Assuntos
Bovinos/fisiologia , Indústria de Laticínios , Lactação/fisiologia , Resultado da Gravidez/veterinária , Animais , Teorema de Bayes , Cruzamento , Indústria de Laticínios/estatística & dados numéricos , Feminino , Fertilidade/fisiologia , Período Pós-Parto , Gravidez
9.
J Dairy Sci ; 96(6): 3907-15, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23548281

RESUMO

Flaxseed is a potent source of the n-3 fatty acid α-linolenic acid (ALA), yet most ALA is lost during ruminal biohydrogenation when ground flaxseed is fed to ruminants. Heat processing and urea formaldehyde condensation polymer (UFCP) treatment of flaxseed were investigated as possible means of protecting ALA from ruminal degradation. Ground flaxseed (GF), heated ground flaxseed (HGF), or UFCP-treated ground flaxseed (UFCPGF) were incubated for 0, 4, 8, and 12h in 4 ruminally cannulated multiparous lactating Holstein cows. Compared with GF, HGF and UFCPGF decreased ruminal disappearance of dry matter, crude protein, and ALA. Pepsin-digestible protein remaining after 12h of ruminal incubation was greater for UFCPGF and HGF than for GF. Twenty-four lactating Holstein cows (207 ± 37 d in milk, 668 ± 66 kg of body weight, and 1.33 ± 0.56 lactations) were then used in a randomized complete block design experiment with a basal feeding period to assess effects of flaxseed treatment on ALA enrichment of plasma and milk as well as lactational performance. No evidence existed that supplementation of HGF and UFCPGF affected dry matter intake, milk fat content, milk protein content, or energy-corrected milk yield, but UFCPGF marginally decreased milk yield compared with HGF. Plasma concentration of ALA was not affected by treatment. Concentrations of n-3 fatty acids and conjugated linoleic acids in milk fat were increased by UFCPGF relative to HGF, but ALA yield was not affected. Taken together, in situ results suggest that heat-treated flaxseed, with or without UFCP treatment, slowed ruminal disappearance of ALA. Feeding UFCP-treated flaxseed failed to alter ALA content of plasma or milk ALA yield relative to heating alone.


Assuntos
Bovinos/fisiologia , Linho/química , Manipulação de Alimentos/métodos , Formaldeído , Polímeros , Rúmen/metabolismo , Ureia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Digestão , Gorduras/análise , Ácidos Graxos Ômega-3/análise , Feminino , Temperatura Alta , Lactação/fisiologia , Leite/química , Sementes/química , Ácido alfa-Linolênico/análise , Ácido alfa-Linolênico/metabolismo , Ácido alfa-Linolênico/farmacocinética
10.
J Dairy Sci ; 96(7): 4340-54, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23684016

RESUMO

As public concern for food animal welfare increases, a need to validate objective pain assessment tools exists in order to formulate animal welfare policies and facilitate regulatory approval of compounds to alleviate pain in livestock in the United States. The aims of this study were (1) to compare the physiological response to pain induced by surgical and nonsurgical (band) castration in calves and (2) to elucidate age-related differences in pain response of calves subjected to different castration methods. Seventy-six Holstein bull calves were blocked by age (≤8-wk and ≥6-mo-old) and randomly assigned to 1 of 4 treatment groups: control (n=20), castration by banding (n=18), cut-and-clamp surgical castration (n=20), and cut-and-pull surgical castration (n=18). Measurements included electroencephalogram, heart rate variability, infrared thermography, electrodermal activity, and concentrations of serum cortisol and plasma substance P before, during, and within 20min following castration. Electroencephalogram recordings showed desynchronization for all treatments, consistent with increased arousal; yet the magnitude of desynchronization was greatest for 6-mo-old calves castrated by cut-and-clamp. Additionally, older calves in the cut-and-pull group showed greater desynchronization than younger calves in the same group. Based on the heart rate variability analysis, 6-mo-old calves in the control or cut-and-pull castration groups showed greater sympathetic tone than younger calves in the same treatment groups. Overall, younger calves showed lower electrodermal activity than older calves. Regardless of treatment, concentrations of cortisol and plasma substance P were greater in 6-mo-old calves relative to their younger counterparts, indicating a more robust response to all treatments in older calves. In summary, neurohormonal and electroencephalographic stress responses of calves to castration were age-specific. Castration by cut-and-clamp showed the most pronounced stress response in 6-mo-old calves. These findings provide evidence that support welfare policies recommending castration at an early age and the use of analgesic compounds at the time of surgical castration especially in older calves. However, the potential long-term negative consequences of early untreated pain must be considered and warrant further investigation.


Assuntos
Envelhecimento/fisiologia , Analgésicos/administração & dosagem , Bem-Estar do Animal , Bovinos/fisiologia , Orquiectomia/veterinária , Estresse Fisiológico/fisiologia , Animais , Doenças dos Bovinos/tratamento farmacológico , Eletroencefalografia/veterinária , Frequência Cardíaca , Hidrocortisona/sangue , Masculino , Orquiectomia/efeitos adversos , Orquiectomia/métodos , Dor/tratamento farmacológico , Dor/veterinária , Medição da Dor/veterinária , Substância P/sangue
11.
Nat Genet ; 27(1): 74-8, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11138002

RESUMO

Mutations or rearrangements in the gene encoding the receptor tyrosine kinase RET result in Hirschsprung disease, cancer and renal malformations. The standard model of renal development involves reciprocal signaling between the ureteric bud epithelium, inducing metanephric mesenchyme to differentiate into nephrons, and metanephric mesenchyme, inducing the ureteric bud to grow and branch. RET and GDNF (a RET ligand) are essential mediators of these epithelial-mesenchymal interactions. Vitamin A deficiency has been associated with widespread embryonic abnormalities, including renal malformations. The vitamin A signal is transduced by nuclear retinoic acid receptors (RARs). We previously showed that two RAR genes, Rara and Rarb2, were colocalized in stromal mesenchyme, a third renal cell type, where their deletion led to altered stromal cell patterning, impaired ureteric bud growth and downregulation of Ret in the ureteric bud. Here we demonstrate that forced expression of Ret in mice deficient for both Rara and Rarb2 (Rara(-/-)Rarb2(-/-)) genetically rescues renal development, restoring ureteric bud growth and stromal cell patterning. Our studies indicate the presence of a new reciprocal signaling loop between the ureteric bud epithelium and the stromal mesenchyme, dependent on Ret and vitamin A. In the first part of the loop, vitamin-A-dependent signals secreted by stromal cells control Ret expression in the ureteric bud. In the second part of the loop, ureteric bud signals dependent on Ret control stromal cell patterning.


Assuntos
Proteínas de Drosophila , Epitélio/efeitos dos fármacos , Rim/embriologia , Mesoderma/efeitos dos fármacos , Vitamina A/farmacologia , Animais , Epitélio/metabolismo , Feminino , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial , Hibridização In Situ , Rim/anormalidades , Rim/efeitos dos fármacos , Rim/metabolismo , Mesoderma/citologia , Mesoderma/metabolismo , Camundongos , Camundongos Transgênicos , Morfogênese/efeitos dos fármacos , Mutação , Técnicas de Cultura de Órgãos , Proteínas Proto-Oncogênicas , Proteínas Proto-Oncogênicas c-ret , RNA Mensageiro/análise , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Receptores Proteína Tirosina Quinases , Transdução de Sinais/efeitos dos fármacos , Vitamina A/administração & dosagem , Vitamina A/genética , Deficiência de Vitamina A/genética , Deficiência de Vitamina A/fisiopatologia
12.
Int J Obes (Lond) ; 36(9): 1215-21, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22158267

RESUMO

AIMS: The pathogenesis of obesity remains incompletely understood and the exploration of the role of novel proteins in obesity may provide important insights into its causes and treatments. Here, we report a previously unidentified role for synphilin-1 in the control of food intake and body weight. Synphilin-1, a cytoplasmic protein, was initially identified as an interaction partner of alpha-synuclein, and has implications in Parkinson's disease pathogenesis related to protein aggregation. SUBJECTS AND METHODS: To study the in vivo role of synphilin-1, we characterized a human synphilin-1 transgenic mouse (SP1) by assessing synphilin-1 expression, plasma parameters, food intake and spontaneous activity to determine the major behavioral changes and their consequences in the development of the obesity phenotype. RESULTS: Expression of human synphilin-1 in brain neurons in SP1 mice resulted in increased food intake, body weight and body fat. SP1 mice also displayed hyperinsulinemia, hyperleptinemia and impaired glucose tolerance. Pair-feeding SP1 mice to amounts consumed by non-transgenic mice prevented the increased body weight, adiposity, hyperinsulinemia and hyperleptinemia demonstrating that these were all the consequences of increased food intake. Transgenic expression of synphilin-1 was enriched in hypothalamic nuclei involved in feeding control, and fasting-induced elevated endogenous synphilin-1 levels at these sites, suggesting that synphilin-1 is an important player in the hypothalamic energy balance regulatory system. CONCLUSION: These studies identify a novel function of synphilin-1 in controlling food intake and body weight, and may provide a unique obesity model for future studies of obesity pathogenesis and therapeutics.


Assuntos
Proteínas de Transporte/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Hiperfagia/metabolismo , Hipotálamo/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Obesidade/metabolismo , Animais , Western Blotting , Peso Corporal , Proteínas de Transporte/genética , Proteínas de Transporte/farmacologia , Modelos Animais de Doenças , Hipotálamo/efeitos dos fármacos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/farmacologia
13.
J Dairy Sci ; 95(10): 5461-75, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22863097

RESUMO

A general belief across the dairy community, both scientific and commercial, is that of an antagonistic association between milk production and reproductive performance of dairy cows. In this article, we critically review the evidence supporting this belief and discuss some of its limitations. Based on the fundamental principles of experimental design and inference, we consider relevant issues that, although critical to the very foundation of the perceived production-reproduction antagonism, seem to have been previously misrepresented or overlooked. In particular, we focus on issues of confounding, randomization, nature of inference, single- versus multiple-trait modeling, cow- versus herd-level modeling, and scope of inference, all within the context of dairy production systems. Taken together, these issues indicate that the production-reproduction antagonism may not be as pervasive as previously believed, suggesting the need for more rigorous methods of scientific investigation on this matter. We revisit the association between milk production and reproductive performance using a novel interdisciplinary approach based on cutting-edge statistical methods that accommodate some of the unique and previously ignored features of this problem. In fact, recent work supports a highly heterogeneous association between milk production and reproductive performance, whereby heterogeneity is partitioned across several scales and driven by many contributing factors, both physiological and managerial. We conclude that the relationship between milk production and reproductive performance is not necessarily that of a universal homogeneous antagonism and suggest better ways to study and even manage this association. A more comprehensive assessment that draws expertise from multiple scientific disciplines will be required to elicit management recommendations targeted to effectively optimize overall performance of dairy cows and commercial herds.


Assuntos
Bovinos/fisiologia , Lactação/fisiologia , Reprodução/fisiologia , Animais , Bovinos/genética , Indústria de Laticínios/métodos , Feminino , Lactação/genética , Leite/metabolismo , Reprodução/genética
14.
J Dairy Sci ; 95(2): 842-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22281347

RESUMO

Productivity of lactating dairy cows fed diets with wet corn gluten feed (WCGF, Sweet Bran, Cargill Inc., Blair, NE) as the primary energy substrate and prairie hay as the primary source of physically effective neutral detergent fiber (peNDF) was assessed relative to a control diet. Forty-eight Holstein cows, 100 to 250 d in milk, were randomly assigned to 1 of 6 pens and pens were randomly assigned to treatment sequence in a replicated 3×3 Latin square. Treatments were a control diet with 18% alfalfa, 18% corn silage, 33% WCGF, and 15% forage NDF (CON); a diet with 20% tallgrass prairie hay, 46% WCGF, and 13% forage NDF (TPH20); and a diet with 14% tallgrass prairie hay, 56% WCGF, and 9% forage NDF (TPH14). Midway through period 2, TPH14 was discontinued due to the high prevalence of diarrhea among cows on that treatment. Data from period 2 for TPH14 pens were discarded, and the pens that had been assigned to TPH14 for period 3 were randomly assigned to the other 2 treatments. Pen-level data were analyzed using linear mixed models, including the random effects of period and pen and the fixed effect of treatment. For animal-level data, additional random effects were introduced to account for subsampling. No evidence for treatment effects was apparent on dry matter intake. Least squares mean milk yields were 36.2, 34.6, and 35.2 kg/d for CON, TPH20, and TPH14, respectively, and were not significantly different. Milk fat concentration was higher for CON and TPH20 than for TPH14, with means of 3.48, 3.41, and 2.82%, respectively. Fat yield was significantly greater for CON compared with TPH20 and TPH14. Milk urea nitrogen was greatest for TPH20 and TPH14 and least for CON, consistent with differences in dietary protein content. Efficiencies, expressed as energy-corrected milk divided by dry matter intake, were 1.47, 1.42, and 1.24 for CON, TPH20, and TPH14, respectively, and were not significantly different. These data indicate that TPH14 did not provide adequate peNDF to support normal rumen function in mid lactation dairy cows; instead, TPH20 may be a feasible diet for use on dairies where high-NDF grass hay and WCGF are available.


Assuntos
Ração Animal , Glutens/farmacologia , Lactação/fisiologia , Zea mays , Ração Animal/análise , Animais , Bovinos , Dieta/veterinária , Feminino , Glutens/administração & dosagem , Lactação/efeitos dos fármacos , Leite/metabolismo , Poaceae , Silagem
15.
J Dairy Sci ; 95(5): 2602-15, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22541489

RESUMO

To determine if dietary medium-chain fatty acids (FA; C(8) to C(14)) may mitigate enteric methane emissions, 24 cows were blocked by body size (n=2) and randomly assigned to 1 sequence of dietary treatments. Diets were fed for 35 d each in 2 consecutive periods. Diets differed in concentrations of coconut oil (CNO; ~75% medium-chain FA): 0.0 (control) or 1.3, 2.7, or 3.3% CNO, dry matter basis. The control diet contained 50% forage (74% from corn silage), 16.5% crude protein (60% from rumen-degradable protein), 34% neutral detergent fiber (NDF; 71% from forage), and 28% starch, dry matter basis. Data and sample collections were from d 29 to 35 in environmentally controlled rooms to measure methane (CH(4)) production. Methane emitted was computed from the difference in concentrations of inlet and outlet air and flux as measured 8 times per day. Control cows emitted 464 g of CH(4)/d, consumed 22.9 kg of DM/d, and produced 34.8 kg of solids-corrected milk/d and 1.3 kg of milk fat/d. Treatment with 1.3, 2.7, or 3.3% dietary CNO reduced CH(4) (449, 291, and 253 g/d, respectively), but concomitantly depressed dry matter intake (21.4, 17.9, and 16.2 kg/d, respectively), solids-corrected milk yield (36.3, 28.4, and 26.8 kg/d, respectively), and milk fat yield (1.4, 0.9, and 0.9 kg/d, respectively). The amount of NDF digested in the total tract decreased with increased dietary CNO concentrations; thus, CH(4) emitted per unit of NDF digested rose from 118 to 128, 153, and 166 g/kg across CNO treatments. Dietary CNO did not significantly affect apparent digestibility of CP but increased apparent starch digestibility from 92 to 95%. No FA C(10) or shorter were detected in feces, and apparent digestibility decreased with increasing FA chain length. Coconut oil concentrations of 2.7 or 3.3% decreased yields of milk FA C(14). The highest milk fat concentration (3.69%; 1.3% CNO) was due to the greatest yields of C(12) to C(16) milk FA. Milk FA concentrations of C(18:2 trans-10,cis-12) were related to increased dietary CNO concentrations and presumably to depressed ruminal NDF digestion. Moderate dietary CNO concentrations (e.g., 1.3%) may benefit lactational performance; however, CNO concentrations greater than or equal to 2.7% depressed dry matter intake, milk yield, milk fat yield, and NDF utilization. If mitigation of enteric CH(4) emissions is due to decreased digestion of dietary NDF, then this will lessen a major advantage of ruminants compared with nonruminants in food-production systems. Thus, CNO has limited use for enteric CH(4) mitigation in lactating dairy cows.


Assuntos
Lactação/efeitos dos fármacos , Metano/biossíntese , Óleos de Plantas/farmacologia , Ração Animal , Animais , Bovinos , Óleo de Coco , Dieta/veterinária , Relação Dose-Resposta a Droga , Ingestão de Alimentos , Feminino
16.
Am Heart J Plus ; 132022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37122821

RESUMO

Study objective: This study sought to evaluate the associations between social determinants of health (SDOH) at the time of first pregnancy and subsequent cardiometabolic health, defined as the development of metabolic syndrome. Design: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study- Monitoring Mothers-to-Be-Heart Health Study) is an ongoing prospective cohort study. Setting: Eight academic medical centers enrolled and continue to follow participants. Participants: 4484 participants followed a mean of 3.2 years from the time of their first pregnancy. Interventions: N/a. Main outcome measure: Unadjusted and adjusted Poisson regression models with robust standard errors were used to obtain relative risks and 95% confidence intervals estimating the risk of metabolic syndrome for each baseline SDOH. In secondary analyses we examined the associations between SDOH and incident hypertension, obesity, and diabetes mellitus. Results: Metabolic syndrome developed in 13.6% of participants. Higher socioeconomic position at the time of pregnancy was associated with lower rates of metabolic syndrome [income > 200% poverty level aRR 0.55 (95% CI, 0.42-0.71), attainment of a bachelor's degree aRR 0.62 (0.46-0.84) or higher aRR 0.50 (0.35-0.71)], while being single [aRR 1.45 (95% CI, 1.18-1.77)] and having low health literacy were associated with a greater risk of metabolic syndrome [aRR 1.98 (95% CI, 1.28-3.07)]. Conclusions: Over a short interval following first pregnancy, participants accumulated high proportions of cardiovascular risk factors and metabolic syndrome, with some risk associated with SDOH. The impact of interventions addressing SDOH in pregnant people on cardiometabolic health should be tested as a means of reducing health inequities at the population level.

17.
Rev Neurol ; 71(10): 365-372, 2020 Nov 16.
Artigo em Espanhol | MEDLINE | ID: mdl-33145747

RESUMO

INTRODUCTION: Epileptic status represents the most frequent neurological emergency in pediatrics. Prolonged febrile seizures represent the most common etiology. Our objective is to update its epidemiology and analyze its evolutionary consequences. PATIENTS AND METHODS: Observational analytical study of retrospective cohorts of children seen in the emergency department with epileptic status between January-2014 and December-2018. Demographic variables, personal history, clinical characteristics, complementary tests and the etiology of the epileptic status followed in our hospital were collected. The evolutionary consequences in terms of neurodevelopment and subsequent epilepsy were analyzed. RESULTS: Of a total of 525,000 emergencies attended during the study, epileptic status cases were 79 in 68 patients (16 cases/100,000 children/year). The symptomatic etiology was the most frequent (35.4%). 20.6% of the patients had a history of prematurity, 30.8% had a deficit of previous neurodevelopment, this being more frequent in case of symptomatic etiology, and 44% were diagnosed with epilepsy. The median duration of seizures was 50 minutes. An acute brain trigger was identified in seven patients. The subsequent neurodevelopmental deficit attributable to epileptic status was 9.1% of patients related to symptomatic etiology and/or a history of prematurity. The development of epilepsy occurred in 10.7%. CONCLUSIONS: The neurodevelopmental disorder attributable to epileptic status affects one in 11 cases. Prematurity was a risk factor per se. Post-epileptic status epilepsy developed in one in 10 cases.


TITLE: Estado epiléptico en pacientes pediátricos: consecuencias evolutivas y actualización epidemiológica.Introducción. El estado epiléptico representa la emergencia neurológica más frecuente en pediatría. Las convulsiones febriles prolongadas representan la etiología más frecuente. Nuestro objetivo es actualizar su epidemiología y analizar sus consecuencias evolutivas. Pacientes y métodos. Estudio observacional analítico de cohortes retrospectivas de niños atendidos en urgencias con estado epiléptico entre enero de 2014 y diciembre de 2018. Se recogieron las variables demográficas, los antecedentes personales, las características clínicas, las pruebas complementarias y la etiología de los estados epilépticos seguidos en nuestro hospital. Se analizaron las consecuencias evolutivas en cuanto a neurodesarrollo y epilepsia ulterior. Resultados. De un total de 525.000 urgencias atendidas durante el estudio, los casos de estado epiléptico fueron 79 en 68 pacientes (16 casos/100.000 niños/año). La etiología sintomática fue la más frecuente (35,4%). El 20,6% de los pacientes presentaba antecedente de prematuridad; el 30,8%, un déficit del neurodesarrollo previo, más frecuente en caso de etiología sintomática, y el 44% estaba diagnosticado de epilepsia. La duración mediana de las crisis fue de 50 minutos. En siete pacientes se identificó un desencadenante cerebral agudo. El déficit del neurodesarrollo ulterior achacable al estado epiléptico fue del 9,1%, y se relacionó con la etiología sintomática o antecedentes de prematuridad. El desarrollo de epilepsia ocurrió en el 10,7%. Conclusiones. La alteración del neurodesarrollo achacable al estado epiléptico afecta a uno de cada 11 casos. La prematuridad fue un factor de riesgo por sí misma. La epilepsia posterior a un estado epiléptico se desarrolló en uno de cada 10 casos.


Assuntos
Emergências , Epilepsia , Convulsões , Criança , Serviço Hospitalar de Emergência , Epilepsia/epidemiologia , Humanos , Pediatria , Estudos Retrospectivos , Convulsões/etiologia
18.
Vet J ; 181(1): 56-62, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19375959

RESUMO

Unsteady hand position can cause discomfort to the horse, potentially leading to conflict behaviours (CB) such as head tossing or tail lashing. Some instructors feel that martingales or elastic rein inserts can reduce discomfort caused by inexperienced and unsteady hands. Others consider these devices to be inappropriate 'crutches'. Four horses and nine riders were tested under three conditions in random order: plain reins, adjustable training martingales (TM), and elasticised rein inserts (RI). Rein-tension data (7s) and behavioural data (30s) were collected in each direction. Rein-tension data were collected via strain-gauge transducers. Behavioural data were assessed using an ethogram of defined behaviours. No differences in the number of CB were observed. Mean rein tension for TM was higher than that of RI or controls. Relative to the withers, the head was lower for horses ridden with martingales. Carefully fitted martingales may have a place in riding schools that teach novices.


Assuntos
Comportamento Animal , Conflito Psicológico , Manobra Psicológica , Cavalos/psicologia , Análise de Variância , Animais , Feminino , Mãos , Cavalos/fisiologia , Humanos , Masculino , Postura
19.
J Dairy Sci ; 91(7): 2901-15, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18565948

RESUMO

Our objective was to determine the accuracy of identifying noncycling lactating dairy cows before the application of a timed artificial insemination (AI) protocol [with or without progesterone supplementation via a controlled internal drug-release (CIDR) insert and 2 different timings of AI] by using heatmount detectors and a single ovarian ultrasound examination. At 6 locations in the Midwest, 1,072 cows were enrolled in a Presynch protocol (2 injections of PGF(2alpha) 14 d apart), with the second injection administered 14 d before initiating the Ovsynch protocol (injection of GnRH 7 d before and 48 h after PGF(2alpha) injection, with timed AI at 0 or 24 h after the second GnRH injection). Heatmount detectors were applied to cows just before the first Presynch injection, assessed 14 d later at the second Presynch injection (replaced when activated or missing), and reassessed at initiation of the Ovsynch protocol. Ovaries were examined for the presence of a corpus luteum (CL) by ultrasound before the initiation of treatment. Treatments were assigned to cows based on the presence or absence of a CL detected by ultrasound: 1) no CL + no CIDR; 2) no CL + CIDR insert for 7 d; and 3) CL present. Further, alternate cows within the 3 treatments were assigned to be inseminated concurrent with the second GnRH injection of Ovsynch (0 h) or 24 h later. Pregnancy was diagnosed at 33 and 61 d after the second GnRH injection. By using low (<1 ng/mL) concentrations of progesterone in serum as the standard for noncycling status, heatmount detectors were activated on a large percentage of noncycling cows (>60%), whereas the single ultrasound examination incorrectly classified noncycling cows only 21% of the time. Conversely, cycling cows (progesterone > or =1 ng/mL) were correctly identified 70 to 78% of the time by heatmount detectors, but 85 to 92% were correctly identified by ultrasound. Overall accuracy of heatmount detectors and ultrasound was 71 and 84%, respectively. Application of progesterone to cows without a CL at the time of the first injection of GnRH reduced the incidence of ovulation but increased the proportions of pregnancies per AI at d 33 or 61 compared with nontreated cows without a CL at the onset of the Ovsynch protocol. Percentages of cows pregnant and pregnancy survival did not differ for cows having a CL before treatment compared with those not having a CL and treated with progesterone. Compared with no response, when a follicle ovulated in response to the first GnRH injection, percentage of cows becoming pregnant after the timed AI increased from 33.3 to 41.6%. Timing of AI at 0 or 24 h after the second GnRH injection did not alter pregnancies per AI, but cows having luteal activity before treatment had improved pregnancies per AI compared with noncycling cows. We conclude that identifying noncycling cows by ultrasound was more accurate than by heatmount detectors. Subsequent progesterone treatment of previously cycling cows not having a CL at the onset of Ovsynch increased the proportion of pregnant cows, equal to that of cows having a CL but not treated with progesterone.


Assuntos
Anovulação/veterinária , Bovinos/fisiologia , Inseminação Artificial/veterinária , Taxa de Gravidez , Progesterona/administração & dosagem , Animais , Anovulação/diagnóstico , Anovulação/diagnóstico por imagem , Corpo Lúteo/diagnóstico por imagem , Dinoprosta/administração & dosagem , Ciclo Estral , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Inseminação Artificial/métodos , Folículo Ovariano/diagnóstico por imagem , Indução da Ovulação/veterinária , Gravidez , Fatores de Tempo , Ultrassonografia
20.
Animal ; 12(7): 1380-1387, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29143703

RESUMO

Environmental regulations as well as economic incentives have resulted in greater use of synthetic amino acids in swine diets. Tryptophan is typically the second limiting amino acid in corn-soybean meal-based diets. However, using corn-based co-products emphasizes the need to evaluate the pig's response to increasing Trp concentrations. Therefore, the objective of these studies was to evaluate the dose-response to increasing standardized ileal digestible (SID) Trp : Lys on growth performance of growing-finishing gilts housed under large-scale commercial conditions. Dietary treatments consisted of SID Trp : Lys of 14.5%, 16.5%, 18.0%, 19.5%, 21.0%, 22.5% and 24.5%. The study was conducted in four experiments of 21 days of duration each, and used corn-soybean meal-based diets with 30% distillers dried grains with solubles. A total of 1166, 1099, 1132 and 975 gilts (PIC 337×1050, initially 29.9±2.0 kg, 55.5±4.8 kg, 71.2±3.4 kg and 106.2±3.1 kg BW, mean±SD) were used. Within each experiment, pens of gilts were blocked by BW and assigned to one of the seven dietary treatments and six pens per treatment with 20 to 28 gilts/pen. First, generalized linear mixed models were fit to data from each experiment to characterize performance. Next, data were modeled across experiments and fit competing dose-response linear and non-linear models and estimate SID Trp : Lys break points or maximums for performance. Competing models included broken-line linear (BLL), broken-line quadratic and quadratic polynomial (QP). For average daily gain (ADG), increasing the SID Trp : Lys increased growth rate in a quadratic manner (P<0.02) in all experiments except for Exp 2, for which the increase was linear (P<0.001). Increasing SID Trp : Lys increased (P<0.05) feed efficiency (G : F) quadratically in Exp 1, 3 and 4. For, ADG the QP was the best fitting dose-response model and the estimated maximum mean ADG was obtained at a 23.5% (95% confidence interval (CI): [22.7, 24.3%]) SID Trp : Lys. For maximum G : F, the BLL dose-response models had the best fit and estimated the SID Trp : Lys minimum to maximize G : F at 16.9 (95% CI: [16.0, 17.8%]). Thus, the estimated SID Trp : Lys for 30 to 125 kg gilts ranged from a minimum of 16.9% for maximum G : F to 23.5% for maximum ADG.


Assuntos
Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Suínos , Triptofano , Animais , Dieta , Feminino , Íleo , Lisina/metabolismo , Suínos/crescimento & desenvolvimento , Triptofano/administração & dosagem , Triptofano/farmacologia
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