Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
Mais filtros

Métodos Terapêuticos e Terapias MTCI
Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-37497194

RESUMO

Stress and burnout are prevalent within the orthopaedic surgery community. Mindfulness techniques have been shown to improve wellness, yet traditional courses are generally time-intensive with low surgeon utilization. We sought to determine whether the introduction of a simple mindfulness-based phone application would help decrease stress, anxiety, and burnout in orthopaedic surgery residents. Methods: Twenty-four residents participated in this prospective, randomized controlled trial. After simple 1:1 randomization, the treatment group received access to a mindfulness-based phone application for 2 months while the control group did not receive access. All participants completed the Perceived Stress Scale, Generalized Anxiety Disorder-7, and Maslach Burnout Inventory with emotional exhaustion (EE), depersonalization (DP), and personal accomplishment subscores to measure stress, anxiety, and burnout at baseline and after 2 months. Paired t tests were used to compare baseline scores and conclusion scores for both groups. Results: There was no difference in baseline burnout scores between groups, but the treatment group had higher stress and anxiety scores at baseline. On average, the treatment group spent approximately 8 minutes per day, 2 days per week using the mindfulness application. After 2 months, the treatment group had significantly decreased stress (mean = -7.42, p = 0.002), anxiety (mean = -6.16, p = 0.01), EE (mean = -10.83 ± 10.72, p = 0.005), and DP (mean = -5.17 ± 5.51, p = 0.01). The control group did not have any significant differences in stress, anxiety, or burnout subscores. Conclusions: Use of a mindfulness-based phone app for 2 months led to significant reductions in stress, anxiety, and burnout scores in orthopaedic surgery residents. Our results support the use of a mindfulness-based app to help decrease orthopaedic resident stress, anxiety, and burnout. Benefits were seen with only modest use, suggesting that intensive mindfulness training programs may not be necessary to effect a change in well-being. The higher baseline stress and anxiety in the treatment group may suggest that mindfulness techniques are particularly effective in those who perceive residency to be more stressful. Level of Evidence: I.

2.
J Dairy Sci ; 103(11): 10108-10121, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32921466

RESUMO

The milk-fed calf has a requirement for essential amino acids (EAA) instead of crude protein (CP). However, most milk replacers (MR) are still formulated to a CP concentration, and although limited amounts of Lys or Met may be added, these MR are not formulated solely on an AA basis. Previous work has demonstrated that feeding a modified MR balanced for specific EAA concentrations of a 24% CP MR, but reducing CP to 22%, resulted in improved growth performance in calves compared with a 24% CP MR. The 56-d objective was to determine if the hypothesis that an EAA MR formulated to the specific EAA concentrations of a 24% CP MR, but reducing CP to 22 (22AA) compared with a standard 22% CP MR would result in similar or enhanced growth performance, while reducing feed costs. Two 56-d studies using forty 3- to 5-d-old Holstein bull calves per study received in 1 lot starting on May 8, 2018 (late-spring cooler) and June 22, 2018 (summer with heat stress) were blocked by body weight (BW) and randomly assigned to 1 of 2 MR treatments. Milk replacer treatments consisted of a standard 22:20 (CP:fat; 22CP) and a 22:20 MR with greater EAA concentrations of a 24% CP MR (22AA). All MR, containing decoquinate and diflubenzuron, were fed at 0.57 kg/d per calf split into 2 feedings at 0630 h and 1800 h for 0 to 14 d via bucket, increased to 0.85 kg/d through 35 d split in 2 feedings, and fed once per day at 0.41 kg/d in the morning with weaning after 42 d. Calves were housed in straw-bedded hutches with ad libitum access to water and 25% CP pelleted calf starter (CS). All data were analyzed as a randomized complete block design with block within study considered random and week as a repeated measurement. Initial BW was similar across all treatments (39.9 ± 2.32 kg). Average daily temperature (i.e., heat stress intensity) tended to be greater for calves in study 2 compared with study 1 (20.5 and 22.9°C for study 1 and 2, respectively). The interaction of study and MR effects were nonsignificant. Calf BW, BW gain, average daily gain, CS intake, total dry matter intake (MR plus CS), feed conversions, and EAA intake (MR plus CS) were similar for calves fed both MR. Study 2 (summer heat stress) resulted in more scours incidences compared with study 1, and 22AA MR formulation tended to increase scours possibly due to synthetic AA addition or greater carbohydrate (lactose) inclusion when AA replaced protein sources. Feed costs as MR and total feed costs were lower for calves fed 22AA MR compared with calves fed 22CP MR. The increased Leu, Lys, Met, Thr, and Val concentrations in the 22AA MR compared with the 22CP MR resulted in similar calf growth performance, but the feed cost was lower for calves fed the 22AA MR, which achieved similar growth performance at a lesser cost under current study conditions, but not enhanced as hypothesized.


Assuntos
Aminoácidos/administração & dosagem , Bovinos/crescimento & desenvolvimento , Suplementos Nutricionais/análise , Substitutos do Leite/administração & dosagem , Ração Animal/análise , Animais , Peso Corporal , Bovinos/fisiologia , Dieta/veterinária , Resposta ao Choque Térmico , Masculino , Distribuição Aleatória , Estações do Ano , Desmame
3.
J Anim Sci ; 98(7)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32632450

RESUMO

Gut health is critically important for growing neonatal calves, and nutritional technologies are needed to prevent disease and stress challenges. Previous work feeding monensin (MON) in combination with an oregano, prebiotic, and cobalt-lactate (EOC) blend had demonstrated improved calf gut health and growth performance. The objective of this study was to evaluate the growth performance of calves fed MON and EOC alone or in combination. Eighty (80) newborn Holstein (37) female and (43) male calves were randomly assigned to one of four treatments arranged in a 2 × 2 factorial (MON and EOC). Treatments were: 1) Control: without MON or EOC added to the calf starter (CS); 2) MON: 50.8 mg/kg CS (Elanco, Greenfield, IN); 3) EOC: 44.1 mg/kg CS (Rum-A-Fresh, Ralco Inc. Marshall, MN); 4) MON + EOC: MON and EOC added to CS. Calves were fed colostrum followed by whole milk through weaning at 42 d, while CS was fed ad libitum through the 70-d experimental period. The MON by EOC interaction was found to be nonsignificant (P > 0.41) for growth performance. Calves fed without or with MON demonstrated similar (P > 0.70) body weight (BW; 68.7 and 68.9 kg without and with MON, respectively), while calves fed EOC demonstrated greater (P < 0.01) BW (67.3 and 70.4 kg without and with EOC, respectively) compared with calves fed without EOC. Calves fed a CS containing MON were similar (P > 0.47) in average daily gain (ADG; 0.88 and 0.91 kg/d) compared with calves fed without MON; however, feeding calves a CS with EOC increased (P < 0.01) ADG (0.84 and 0.95 kg/d) by 13% through the 70-d experimental period compared with calves not fed EOC. Frame measurements indicated that the greater ADG was due to increased (P < 0.10) frame growth for calves fed essential oils (EO) compared with calves fed without EO. A MON by EOC interaction (P < 0.01) for serum propionate concentration demonstrated calves fed MON + EOC and EOC were greater (P < 0.05) compared with calves fed Control, while calves fed MON were intermediate and different (P < 0.05). Feeding calves a CS with EOC increased (P < 0.04) immunoglobulin A, immunoglobulin G, and immunoglobulin M concentrations compared with calves fed without EOC. A MON by EOC interaction was detected (P < 0.01) for total tract starch digestibility for calves fed EOC or MON + EOC demonstrating greater (P < 0.05) starch digestibilities than Control-fed calves. These data demonstrate that EOC and MON fed in combination was not beneficial for enhancing the growth performance, but that calf growth performance can be improved with EOC compared with MON.


Assuntos
Bovinos/fisiologia , Cobalto/farmacologia , Dieta/veterinária , Monensin/farmacologia , Origanum , Prebióticos , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Peso Corporal , Cobalto/administração & dosagem , Colostro , Feminino , Masculino , Leite , Monensin/administração & dosagem , Óleos Voláteis/administração & dosagem , Óleos Voláteis/farmacologia , Gravidez , Amido
4.
J Dairy Sci ; 103(9): 8119-8129, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32684446

RESUMO

Our previous work indicated that feeding oregano essential oil (OEO) in combination with monensin (MON) may not be mutually beneficial to dairy calf growth performance. To evaluate this observation further, a 240-d long-term growth experiment was conducted using 12 young growing Holstein bulls using a 2 × 2 factorial treatment arrangement. Main factors were OEO and MON arranged in 4 individual treatments: (1) ration fed without OEO or MON (control), (2) OEO fed at 26 mg/kg of dry matter (DM), (3) MON fed at 25 mg/kg of DM, and (4) OEO and MON fed in combination (OEO+MON). Holstein bulls were 70 d of age and similar in body weight (BW; 93.3 ± 4.54 kg) and individually fed for 240 d. The targeted feeding rates of OEO and MON were blended into 200 g of concentrate and top dressed each morning to a corn stalklage-based ration. Body weights, frame measurements, and blood samples were collected monthly. Interactions of OEO by MON were detected for BW, BW gain, average daily gain, and a trend for feed conversion. Bulls fed OEO or MON demonstrated greater final BW (368, 385, 381, and 358 kg for control, OEO, MON, and OEO+MON, respectively), and BW gains (278, 292, 285, and 265 kg) and average daily gain (1.16, 1.22, 1.19, 1.11 kg/d) were greatest for bulls fed OEO or MON compared with bulls fed OEO+MON; bulls fed the control were intermediate and similar to bulls fed MON. Intake of DM was greater for bulls fed OEO (6.55, 6.99, 6.60, and 6.42 kg/d) compared with bulls fed remaining treatments. Frame growth gain measurements for heart girth, abdominal girth, withers height, body length, and cannon bone circumference were similar for bulls fed all treatments. Serum triglyceride (0.23, 0.25, 0.28, and 0.24 mmol/L) concentrations were greater for bulls fed MON compared with bulls fed the control and OEO+MON, and bulls fed OEO were intermediate and similar. Cholesterol (2.06, 2.29, 2.20, and 2.07 mmol/L) concentrations were greater for bulls fed OEO compared with bulls fed the control and OEO+MON, and bulls fed MON were intermediate and similar. Serum antioxidant measurements were similar for bulls fed all treatments. Serum IgA, IgG, and IgM concentrations were similar for bulls fed all treatments. Feeding OEO or MON separately can improve growth performance of growing Holstein bulls. We do not know why the combination of OEO and MON is antagonistic to growth performance of Holstein bulls. However, these technologies should not be fed in combination to growing dairy cattle.


Assuntos
Suplementos Nutricionais , Crescimento/efeitos dos fármacos , Monensin/farmacologia , Óleos Voláteis/farmacologia , Origanum/química , Ração Animal , Animais , Peso Corporal/efeitos dos fármacos , Bovinos , Dieta/veterinária , Masculino , Monensin/administração & dosagem , Óleos Voláteis/administração & dosagem
5.
J Anim Sci ; 98(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32266373

RESUMO

The milk-fed calf has a requirement for amino acids (AA) instead of crude protein (CP); however, most milk replacers (MR) are still formulated for CP concentrations. Previous work has demonstrated that feeding a modified MR (24:20; CP:fat @ 0.64 kg/d) improved calf growth performance compared with standard (20:20 @ 0.57 kg/d) and accelerated MR (26:16 @ 0.78 kg/d). The 56-d study objective was to determine if feeding an MR formulated using synthetic AA to achieve the AA concentrations of a 24:20 MR while reducing CP results in similar or enhanced growth performance and/or reduce cost compared with standard MR formulations. Eighty 3- to 5-d-old Holstein bull calves received in two lots (40) within the same week were blocked by body weight (BW) and randomly assigned to one of four MR treatments consisting of 20:20 (20), 22:20 (22), 24:20 (24), and a 22:20 having the AA concentrations of the 24, but with reduced CP (22AA). All MR contain decoquinate and were fed at 0.57 kg/calf daily split into 2×/d feeding for 14 d via bucket, increased to 0.85 kg/calf daily in two feedings until 35 d, and then fed 1×/d at 0.41 kg/calf daily with weaning after day 42. Calves were housed in straw-bedded hutches with ad libitum access to water and pelleted calf starter (CS). All data were statistically analyzed as a randomized complete block design with block considered random with week as a repeated measurement. Initial BW was similar (P > 0.10) across all treatments (42.4 ± 2.2 kg). Calves fed 22AA MR demonstrated greater (P < 0.05) BW compared with calves fed the 24 MR, and calves fed the 20 and 22 MR being intermediate and similar (P > 0.10; 78.7, 78.8, 76.5, and 81.8 kg for 20, 22, 24, and 22AA, respectively). CS intake was greater (P < 0.05) for calves fed 22AA (0.74, 0.78, 0.65, and 0.81 kg/d) compared with calves fed the 20 and 24, but similar (P > 0.10) to calves fed 22. Calves fed 24 MR demonstrated the lowest CS intake. This study demonstrates that similar growth performance can be achieved by feeding an AA fortified MR having a lesser CP concentration, which might reduce feed costs.


Assuntos
Aminoácidos/farmacologia , Suplementos Nutricionais/análise , Substitutos do Leite/farmacologia , Ração Animal/análise , Animais , Peso Corporal/efeitos dos fármacos , Bovinos , Dieta/veterinária , Masculino , Leite , Distribuição Aleatória , Desmame
6.
J Dairy Sci ; 103(3): 2315-2323, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31980222

RESUMO

Essential oils extracted from specific plants can exhibit antimicrobial properties that make them potential antibiotic alternatives. The objective was to evaluate an essential oil and prebiotic combination (EOC) on the growth, development, and health status of growing neonatal calves. Forty Holstein newborn calves were blocked by birth date and alternately assigned to 1 of 2 treatments. Treatments were a pelleted calf starter (CS) without (control) or with EOC at 44.1 ppm. Calves were fed the experimental CS for ad libitum consumption from 3 d of age through the end of the 70-d experiment. Calves were fed 2 L of whole milk twice daily to 10 d of age, then 3 L twice daily through d 35, and then fed 3 L once daily with abrupt weaning occurring after 42 d of age. The average daily gain (0.78 and 0.87 kg/d for control and EOC, respectively) was greater for calves fed EOC compared with calves fed the control. Calves fed EOC demonstrated greater dry matter intake (1.63 and 1.74 kg/d) compared with calves fed the control. Feed conversion ratio (0.62 and 0.65 kg of gain/kg of dry matter intake) was greater for calves fed EOC compared with calves fed the control. At 70 d of age, calves fed EOC demonstrated increased body frame measurements (hip height, body length, heart girth, abdominal girth, and pastern) compared with calves fed the control. The incidence of scours score 4 (mild diarrhea) was 3.5 incidences lower for calves fed EOC compared with calves fed the control, whereas the incidence of scours score 5 (severe diarrhea) for calves fed EOC was 0.5 incidences lower than calves fed the control. Blood concentrations of IgG and IgM on d 14, IgA on d 28, and total serum protein on d 42 were all greater for calves fed EOC compared with calves fed the control. The blood volatile fatty acid concentrations were greater for calves fed EOC compared with calves fed the control, which indicated enhanced ruminal development. Total-tract digestibility of dry matter, crude protein, acid detergent fiber, neutral detergent fiber, starch, and many minerals were increased for calves fed EOC compared with calves fed the control. The inclusion of an EOC blend into a CS demonstrates promising benefits for enhancing calf growth, ruminal development, gut health, nutrient digestibility, and immunity. The use of an EOC blend can be a plausible alternative to feeding subtherapeutic antibiotics for improving calf performance, health, and immunity.


Assuntos
Ração Animal/análise , Bovinos/fisiologia , Ácidos Graxos Voláteis/sangue , Óleos Voláteis/administração & dosagem , Óleos de Plantas/administração & dosagem , Prebióticos/administração & dosagem , Animais , Animais Recém-Nascidos , Peso Corporal , Bovinos/crescimento & desenvolvimento , Bovinos/imunologia , Dieta/veterinária , Ingestão de Alimentos , Feminino , Masculino , Leite/química , Leite/metabolismo , Nutrientes , Desmame
7.
J Dairy Sci ; 103(3): 2303-2314, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31954586

RESUMO

Different inclusion rates of oregano essential oil (OEO) were investigated for their effects on ruminal in vitro fermentation parameters, total gas, methane production, and bacterial communities. Treatments were (1) control, 0 mg/L of OEO (CON); 13 mg/L (OEO1); 52 mg/L (OEO2); 91 mg/L (OEO3); and 130 mg/L (OEO4), each incubated with 150 mL of buffered rumen fluid and 1,200 mg of substrate for 24 h using the Ankom in vitro gas production system (Ankom Technology Corp., Fairport, NY). Treatment responses were statistically analyzed using polynomial contrasts. Digestibility of DM, NDF, and ADF increased quadratically with increasing OEO inclusion rates. Digestibility of DM and NDF were highest for OEO2, whereas ADF digestibility was highest for OEO3, compared with CON, with the remaining treatments being intermediate and similar. Ammonia nitrogen concentrations decreased from CON at a quadratic rate with increasing OEO inclusion rates, and OEO2 had the lowest concentration compared with the other groups. Total VFA, acetate, propionate, butyrate, valerate, and isovalerate concentrations linearly decreased with increasing OEO inclusion rates. Total gas production levels by CON and OEO4 were greater than those of OEO1, OEO2, and OEO3 in a quadratic response, and methane production linearly decreased from CON, compared with OEO4, at a decreasing rate with OEO inclusion rates. As determined by 16S rRNA sequencing, the α biodiversity of ruminal bacteria was similar among OEO inclusion rates. Increasing OEO inclusion rates linearly increased the relative abundance of Prevotella and Dialister bacteria. Several bacteria demonstrated different polynomial responses, whereas several bacteria were similar among increasing OEO inclusion rates. These results suggested that OEO supplementation can modify ruminal fermentation to alter VFA concentrations and reduce methane emissions by extensively altering the ruminal bacterial community, suggesting an optimal feeding rate for future animal studies of approximately 52 mg/L for mature ruminants.


Assuntos
Bactérias/classificação , Bovinos/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Metano/metabolismo , Óleos Voláteis/administração & dosagem , Origanum/química , Ovinos/fisiologia , Amônia/metabolismo , Ração Animal/análise , Animais , Bactérias/genética , Dieta/veterinária , Digestão/efeitos dos fármacos , Feminino , Fermentação/efeitos dos fármacos , Masculino , Nitrogênio/metabolismo , Óleos de Plantas/administração & dosagem , RNA Ribossômico 16S/genética , Rúmen/metabolismo
8.
PLoS One ; 14(5): e0217054, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31107883

RESUMO

Oregano essential oil (OEO), which has antimicrobial properties, may be used for altering the ruminal pH and microbial populations of sheep, as observed by the altered volatile fatty acid patterns. To further elucidate the effects of OEO on ruminal pH and microbial populations of sheep, 3 German merino sheep × local sheep crossbred rams with permanent ruminal fistulas were randomly assigned to a 3 × 3 Latin square design with 12-d periods. The treatments were as follows: control (CON); OEO4: OEO supplied at 4 g•d-1; and OEO7: OEO supplied at 7 g•d-1. Starting on day 11, rumen fluid was collected at 0 h, and at 4, 8, 12, 24 and 48 h after supplying OEO, and then pH values of rumen fluid were immediately measured. The abundance of microbial populations was determined by using qPCR. The ruminal pH values were similar among the sheep from all treatments. The abundance of ruminal fungi was higher for the sheep supplied OEO7 compared with the sheep supplied CON and OEO4, especially at 4 and 12 h. The abundance of ruminal protozoa decreased with supplied OEO, indicating that OEO could inhibit the protozoa. The abundance of the total ruminal bacteria was similar for the sheep from all treatments, but R. flavefaciens, R. albus and F. succinogenes increased in the sheep supplied OEO4 compared with those in the sheep supplied CON, however, the sheep supplied OEO7 had higher abundances of R. flavefaciens than the sheep supplied CON. These results demonstrated that supplying OEO to sheep did not affect the ruminal pH but could shift the rumen microbial population to one with less protozoa. Supplying OEO can preferentially enhance the growth of certain rumen microbial populations, but the shifts were influenced by the supply rate. Therefore, supplying low amount (i.e. 4 g•d-1) of OEO could have positive effects on ruminal microbial populations, whereas supplying elevated doses of OEO could be detrimental to those same ruminal microbial populations.


Assuntos
Óleos Voláteis/farmacologia , Origanum/química , Óleos de Plantas/farmacologia , Rúmen/efeitos dos fármacos , Rúmen/microbiologia , Ovinos/microbiologia , Ração Animal , Animais , Anti-Infecciosos/farmacologia , Primers do DNA , Dieta/veterinária , Suplementos Nutricionais , Ácidos Graxos/química , Feminino , Fermentação , Concentração de Íons de Hidrogênio , Lactação/efeitos dos fármacos , Masculino , RNA Ribossômico 16S/metabolismo
9.
BMC Microbiol ; 19(1): 30, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717674

RESUMO

BACKGROUND: Essential Oils (EO) are complex mixtures of plant secondary metabolites that have been proposed as promising feed additives for mitigating methane and ammonia emissions. We have previously demonstrated that Essential Oil-Cobalt (EOC) supplementation resulted in increased average daily gain and improved phenotypes (cashmere fiber traits, carcass weight, and meat quality) when cashmere goats received supplementation at approximately 2 mg/kg of body weight. However, the ruminal microbiological effects of EO remain poorly understood with regard to the extent to which ruminal populations can adapt to EO presence as feed ingredients. The effects of varying levels of EO require additional study. RESULTS: In this study, we conducted metagenomic analyses using ruminal fluid samples from three groups (addition of 0, 52, and 91 mg) to evaluate the influence of dietary EOC supplementation on goat rumen bacterial community dynamics. EOC addition resulted in changes of ruminal fermentation types and the EOC dose strongly impacted the stability of ruminal microbiota. The Bacteroides sp. and Succinivibrio sp. type bacterial community was positively associated with improved volatile fatty acid production when the diet was supplemented with EOC. CONCLUSIONS: A clear pattern was found that reflected rapid fermentative improvement in the rumen, subsequent to butyrate metabolism and EOC based feed additives may affect rumen microbes to further improve feed conversion. This observation indicates that EOC can be safely used to enhance animal productivity and to reduce ammonia and waste gas emissions, thus positively impacting the environment.


Assuntos
Cobalto/administração & dosagem , Suplementos Nutricionais , Metagenômica , Microbiota/efeitos dos fármacos , Óleos Voláteis/administração & dosagem , Rúmen/microbiologia , Ração Animal/análise , Animais , Digestão , Ácidos Graxos Voláteis/metabolismo , Fermentação , Cabras , Masculino , Metano/metabolismo
10.
Sci Rep ; 8(1): 11634, 2018 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-30072796

RESUMO

Essential oils (EO) are secondary metabolites usually made up of terpenoids and phenylpropanoids and have antimicrobial properties. However, the feeding effects of EO-Cobalt (EOC) on the performance of goats are largely unknown. Herein we investigated and reported the effects of dietary EOC (0, 52, and 91 mg daily) on fiber producing cashmere goats. We determined the resulting phenotypes including live growth, carcass weight, meat quality, and cashmere fiber traits. We show that dietary supplement of EOC significantly promoted average daily gain (P < 0.05), and significantly improved carcass weight, and meat and hair fiber quality (P < 0.05). We further conducted RNA-seq using skin and liver tissues from each group to assess the molecular mechanism conferring these phenotypic changes. A total of 191 differentially expressed genes were found in the skin tissues (0 vs 91 mg), while 1,127 DEGs were found in livers. Analyses of liver samples for differential gene action and functional prediction found that EOC stimulated physiological changes in the body's immune system at both blood and cell levels. Our results demonstrated the potential of using EO-based feed ingredient to improve animal growth performance, meat quality and fiber quality, and further illustrated the molecular basis that contribute to phenotypes at physiological levels.


Assuntos
Cobalto/farmacologia , Suplementos Nutricionais , Qualidade dos Alimentos , Cabras/metabolismo , Carne , Óleos Voláteis/farmacologia , Pele/metabolismo , Ração Animal , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/metabolismo , Masculino
11.
J Biol Chem ; 277(41): 38322-7, 2002 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-12167642

RESUMO

The hepatitis C virus (HCV) NS5B protein encodes an RNA-dependent RNA polymerase (RdRp), the primary catalytic enzyme of the HCV replicase complex. We established a biochemical RNA synthesis assay, using purified recombinant NS5B lacking the C-terminal 21 amino acid residues, to identify potential polymerase inhibitors from a high throughput screen of the GlaxoSmithKline proprietary compound collection. The benzo-1,2,4-thiadiazine compound 1 was found to be a potent, highly specific inhibitor of NS5B. This agent interacts directly with the viral polymerase and inhibits RNA synthesis in a manner noncompetitive with respect to GTP. Furthermore, in the absence of an in vitro-reconstituted HCV replicase assay employing viral and host proteins, the ability of compound 1 to inhibit NS5B-directed viral RNA replication was determined using the Huh7 cell-based HCV replicon system. Compound 1 reduced viral RNA in replicon cells with an IC(50) of approximately 0.5 microm, suggesting that the inhibitor was able to access the perinuclear membrane and inhibit the polymerase activity in the context of a replicase complex. Preliminary structure-activity studies on compound 1 led to the identification of a modified inhibitor, compound 4, showing an improvement in both biochemical and cell-based potency. Lastly, data are presented suggesting that these compounds interfere with the formation of negative and positive strand progeny RNA by a similar mode of action. Investigations are ongoing to assess the potential utility of such agents in the treatment of chronic HCV disease.


Assuntos
Inibidores Enzimáticos/farmacologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/enzimologia , RNA Polimerase Dependente de RNA/metabolismo , Tiadiazinas/farmacologia , Proteínas não Estruturais Virais/metabolismo , Linhagem Celular , Dicroísmo Circular , Avaliação Pré-Clínica de Medicamentos , Estabilidade Enzimática , Hepacivirus/genética , Humanos , Estrutura Molecular , Desnaturação Proteica , RNA/metabolismo , RNA Polimerase Dependente de RNA/antagonistas & inibidores , RNA Polimerase Dependente de RNA/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Temperatura , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA