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1.
J Anim Physiol Anim Nutr (Berl) ; 102(1): e442-e448, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28710783

RESUMEN

Recent technological advances in the human food industry with respect to meat processing have decreased the availability of animal proteins to the pet food industry which typically formulates diets with an excess of animal protein. In the long term, this is not sustainable; thus, alternative protein sources need to be investigated. This study examined three canine diets, comparing a typical animal protein-based diet (control) with two experimental diets where the animal protein was substituted in part with vegetable protein (formulated based either on total protein or amino acid content) using a broiler model. Each diet was fed to six cages each containing two birds from day 15, 18 cages in total (36 birds). Excreta were collected from days 19 to 21. On day 23, birds were euthanized and weighed, and their ileal digesta were collected and pooled for each cage. In addition, one leg per cage was collected for evaluation of muscle mass. Results showed no significant difference in animal performance (feed intake or live weight gain) or muscle to leg proportion across the diets. Birds fed the control diet and the diet balanced for amino acid content exhibited the greatest coefficients of apparent metabolizability for nitrogen (p < .001). Birds fed the diets that contained partial replacement of animal with vegetable protein generally had greater ileal digestibility of amino acids compared to birds fed the control (animal protein) diet. Analysis of excreta showed no dietary difference in terms of dry matter content; however, birds fed the diet balanced for total protein and the diet balanced for amino acid content had significantly greater excreta nitrogen than the control (p = .038). Overall, the study suggests vegetable proteins when formulated based on amino acid content are a viable alternative to animal proteins in canine diets.


Asunto(s)
Alimentación Animal/análisis , Pollos/fisiología , Dieta/veterinaria , Proteínas en la Dieta/análisis , Perros , Verduras/química , Aminoácidos/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Digestión/fisiología , Íleon/fisiología
2.
J Anim Physiol Anim Nutr (Berl) ; 101(4): 658-666, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27562881

RESUMEN

Rapeseed proteins have been considered as being poorly digestible in the gut of non-ruminants. The aim of the study was to assess the digestibility of napin and cruciferin in ileal digesta of broiler chickens, testing sixteen samples of rapeseed co-products with protein levels ranging from 293 g/kg to 560 g/kg dry matter. Each sample was included into a semi-synthetic diet at a rate of 500 g/kg and evaluated with broiler chickens in a randomised design. Dietary and ileal digesta proteins were extracted and identified by gel-based liquid chromatography-tandem mass spectrometry (LC-MS/MS). Three isomers of napin (a 2S albumin) and nine cruciferins (an 11S globulin) were identified in the rapeseed co-products, whereas six endogenous enzymes such as trypsin (I-P1, II-P29), chymotrypsin (elastase and precursor), carboxypeptidase B and α-amylase were found in the ileal digesta. It is concluded that as none of the rapeseed proteins were detected in the ileal digesta, rapeseed proteins can be readily digested by broiler chickens, irrespective of the protein content in the diet.


Asunto(s)
Albuminas 2S de Plantas/metabolismo , Alimentación Animal/análisis , Antígenos de Plantas/metabolismo , Brassica rapa/química , Pollos/metabolismo , Proteínas de Almacenamiento de Semillas/metabolismo , Albuminas 2S de Plantas/química , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Antígenos de Plantas/química , Dieta/veterinaria , Masculino , Proteínas de Almacenamiento de Semillas/química
3.
Br Poult Sci ; 56(4): 494-502, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26098705

RESUMEN

There is much interest in quantifying the nutritional value of UK wheat distillers dried grains with solubles (W-DDGS) for livestock species. A study was designed to evaluate caecal parameters (pH, short chain fatty acids (SCFAs) and bacterial diversity) in layer hens fed on balanced diets containing graded concentrations of W-DDGS. A total of 32 layer hens (Bovans Brown strain at 27 weeks of age) were randomly allocated to one of 4 dietary treatments containing W-DDGS at 0, 60, 120 or 180 g/kg. Each treatment was fed to 8 replicate individually housed layer hens over a 5-d acclimatisation period, followed by a 4-week trial. Individual feed intakes were monitored and all eggs were collected daily for weeks 2, 3 and 4 of the trial, weighed and an assessment of eggshell "dirtiness" made. All hens were culled on d 29 and caecal pH and SCFAs measured. Polymerase chain reaction denaturing gradient gel electrophoresis of the bacterial 16 S rDNA gene was used to assess total bacterial diversity of luminal caecal content from hens fed the 0 and 180 g W-DDGS/kg diets. Unweighted pair group method with arithmetic mean (UPGMA) dendrograms were generated from DGGE banding patterns. Increasing W-DDGS dietary concentrations resulted in a more acidic caecal environment. Caecal SCFAs were unaffected by diet aside from a quadratic effect for molar proportions of isobutyric acid. Diversity profiles of the bacterial 16S rRNA gene from luminal caecal contents were unaffected by W-DDGS inclusion. The results of the current study suggest that W-DDGS can be successfully formulated into nutritionally balanced layer diets (supplemented with xylanase and phytase) at up to 180 g/kg with no detrimental effects to the caecal environment.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales/efectos de los fármacos , Ciego/metabolismo , Ciego/microbiología , Pollos/fisiología , Triticum/química , Alimentación Animal/análisis , Animales , Bacterias/aislamiento & purificación , Ciego/efectos de los fármacos , ADN Bacteriano/análisis , Dieta/veterinaria , Relación Dosis-Respuesta a Droga , Grano Comestible/química , Femenino , Distribución Aleatoria
4.
Br J Cancer ; 110(7): 1681-7, 2014 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-24594998

RESUMEN

BACKGROUND: Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention trial. We assess the uptake of tamoxifen in a consecutive series of premenopausal women not in a trial and explore the reasons for uptake through interviews. METHODS: All eligible women between 33 and 46 years at ≥17% lifetime risk of breast cancer and undergoing annual mammography in our service were invited to take a 5-year course of tamoxifen. Reasons for accepting (n=15) or declining (n=15) were explored using semi-structured interviews. RESULTS: Of 1279 eligible women, 136 (10.6%) decided to take tamoxifen. Women >40 years (74 out of 553 (13.4%)) and those at higher non-BRCA-associated risk were more likely to accept tamoxifen (129 out of 1109 (11.6%)). Interviews highlighted four themes surrounding decision making: perceived impact of side effects, the impact of others' experience on beliefs about tamoxifen, tamoxifen as a 'cancer drug', and daily reminder of cancer risk. CONCLUSIONS: Tamoxifen uptake was similar to previously ascertained uptake in a randomised controlled trial (IBIS-I). Concerns were similar in women who did or did not accept tamoxifen. Decision making appeared to be embedded in the experience of significant others.


Asunto(s)
Antineoplásicos Hormonales/administración & dosificación , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/prevención & control , Tamoxifeno/administración & dosificación , Mujeres/psicología , Adulto , Instituciones Oncológicas , Toma de Decisiones , Femenino , Humanos , Entrevistas como Asunto , Persona de Mediana Edad , Premenopausia/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo
5.
Poult Sci ; 93(5): 1178-85, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24795310

RESUMEN

As distillers dried grains with solubles (DDGS) become increasingly available, it is important to determine their nutritional value for precise feed formulation. The accurate determination of digestibility is crucial, and it is known that the methods used will affect the values obtained. An experiment was designed to determine and compare the standardized ileal digestibility (SID) of amino acids from wheat DDGS using a semisynthetic diet and a difference method using 4 further diets based on corn, wheat, corn DDGS, and wheat DDGS. Eighty 1-d-old male broilers were fed a commercial starter diet until d 21. Between d 21 and 23, they were fed test diets in order to adapt to those diets before the trial took place between d 24 and 27. The trial period took place between d 24 and 27. Feed intake was measured, excreta collected, and at d 27, all birds were culled and ileal digesta was collected for the determination of apparent ileal digestibility and SID of amino acids. Values determined were similar to those reported elsewhere in the literature, although SID values for lysine were particularly low, being 0.26, 0.27, or 0.32, measured in semisynthetic, corn, or wheat diet backgrounds, respectively. It appeared that diet type employed was influential in the values obtained. The SID values for methionine, cysteine, methionine plus cysteine, and arginine were significantly lower (P < 0.05) when measured in semisynthetic diet backgrounds than wheat- or corn-based diets. It appears that dextrose and possibly purified starch have a detrimental impact on the broiler digestive tract. This may affect all digestibility methodologies in which such a diet base is used.


Asunto(s)
Aminoácidos/metabolismo , Crianza de Animales Domésticos/métodos , Pollos/fisiología , Digestión , Íleon/metabolismo , Triticum/química , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Pollos/crecimiento & desarrollo , Dieta/veterinaria , Masculino , Valor Nutritivo , Triticum/metabolismo
6.
Poult Sci ; 91(1): 8-25, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22184424

RESUMEN

The aim of this study was to apply the life cycle assessment (LCA) method, from cradle to gate, to quantify the environmental burdens per 1,000 kg of expected edible carcass weight in the 3 main broiler production systems in the United Kingdom: 1) standard indoor, 2) free range, and 3) organic, and to identify the main components of these burdens. The LCA method evaluates production systems logically to account for all inputs and outputs that cross a specified system boundary, and it relates these to the useful outputs. The analysis was based on an approach that applied a structural model for the UK broiler industry and mechanistic submodels for animal performance, crop production, and major nutrient flows. Simplified baseline feeds representative of those used by the UK broiler industry were used. Typical UK figures for performance and mortality of birds and farm energy and material use were applied. Monte Carlo simulations were used to quantify the uncertainties in the outputs. The length of the production cycle was longer for free-range and organic systems compared with that of the standard indoor system, and as a result, the feed consumption and manure production per bird were higher in the free-range and organic systems. These differences had a major effect on the differences in environmental burdens between the systems. Feed production, processing, and transport resulted in greater overall environmental impacts than any other components of broiler production; for example, 65 to 81% of the primary energy use and 71 to 72% of the global warming potential of the system were due to these burdens. Farm gas and oil use had the second highest impact in primary energy use (12-25%) followed by farm electricity use. The direct use of gas, oil, and electricity were generally lower in free-range and organic systems compared with their use in the standard indoor system. Manure was the main component of acidification potential and also had a relatively high eutrophication potential. The LCA method allows for comparisons between systems and for the identification of hotspots of environmental impacts that could be subject to mitigation.


Asunto(s)
Crianza de Animales Domésticos , Pollos , Monitoreo del Ambiente/métodos , Contaminación Ambiental/prevención & control , Carne , Alimentación Animal , Crianza de Animales Domésticos/economía , Animales , Estiércol , Modelos Teóricos , Reino Unido
7.
Poult Sci ; 91(1): 26-40, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22184425

RESUMEN

The aim of this study was to apply a life cycle assessment (LCA) method, from cradle to gate, to quantify the environmental burdens per 1,000 kg of eggs produced in the 4 major hen-egg production systems in the United Kingdom: 1) cage, 2) barn, 3) free range, and 4) organic. The analysis was based on an approach that applied a structural model for the industry and mechanistic submodels for animal performance, crop production, and nutrient flows. Baseline feeds representative of those used by the UK egg production industry were used. Typical figures from the UK egg production industry, feed intake, mortality of birds, farm energy, and material use in different systems were applied. Monte Carlo simulations were used to quantify the uncertainties in the outputs and allow for comparisons between the systems. The number of birds required to produce 1,000 kg of eggs was highest in the organic and lowest in the cage system; similarly, the amount of feed consumed per bird was highest in the organic and lowest in the cage system. These general differences in productivity largely affected the differences in the environmental impacts between the systems. Feed production, processing, and transport caused greater impacts compared with those from any other component of production; that is, 54 to 75% of the primary energy use and 64 to 72% of the global warming potential of the systems. Electricity (used mainly for ventilation, automatic feeding, and lighting) had the second greatest impact in primary energy use (16-38%). Gas and oil (used mainly for heating in pullet rearing and incineration of dead layer birds) used 7 to 14% of the total primary energy. Manure had the greatest impact on the acidification and eutrophication potentials of the systems because of ammonia emissions that contributed to both of these potentials and nitrate leaching that only affected eutrophication potential. The LCA method allows for comparisons between systems and for the identification of hotspots of environmental impacts that could be subject to mitigation.


Asunto(s)
Crianza de Animales Domésticos , Pollos , Huevos , Monitoreo del Ambiente/métodos , Contaminación Ambiental/prevención & control , Alimentación Animal , Crianza de Animales Domésticos/economía , Animales , Estiércol , Modelos Teóricos , Reino Unido
8.
Intern Med J ; 43(5): 613-4, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23668284
9.
Int J Ment Health Syst ; 12: 28, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29881451

RESUMEN

BACKGROUND: This article provides an overview of the current and projected climate change risks and impacts to mental health and provides recommendations for priority actions to address the mental health consequences of climate change. DISCUSSION AND CONCLUSION: The authors argue the following three points: firstly, while attribution of mental health outcomes to specific climate change risks remains challenging, there are a number of opportunities available to advance the field of mental health and climate change with more empirical research in this domain; secondly, the risks and impacts of climate change on mental health are already rapidly accelerating, resulting in a number of direct, indirect, and overarching effects that disproportionally affect those who are most marginalized; and, thirdly, interventions to address climate change and mental health need to be coordinated and rooted in active hope in order to tackle the problem in a holistic manner. This discussion paper concludes with recommendations for priority actions to address the mental health consequences of climate change.

10.
Br Poult Sci ; 48(6): 703-12, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18085453

RESUMEN

1. Increasing proportions of soybeans in poultry diets have highlighted the importance of correct processing to inactivate the anti-nutritional factors present whilst maintaining protein quality. 2. Ground full fat soybeans (FFSB) were extruded using a Clextral laboratory model twin-screw extruder with 0.75 l/h of water and end barrel temperatures of 90, 110, 130 and 160 degrees C resulting in trypsin inhibitor activities (TIA) of 14.8, 9.6, 4.5 and 1.9 mg/g sample. 3. The 4 extrudates were used at three different inclusion levels: 200, 400 and 600 g/kg semi-synthetic diet and fed to male Ross broiler chicks from d 19 to d 26. Digesta samples were taken for measurement of coefficient of ileal apparent amino acid digestibility (CIAD) and both pancreas and whole bird weights were measured. 4. Concentration of ileal apparent digestible lysine was increased from 10.53 to 17.63 g/kg FFSB by increasing extrusion temperature from 90 to 160 degrees C. CIAD of lysine was also improved from 0.58 to 0.86. Other amino acids showed similar improvements in both their ileal apparent digestible concentration and CIAD. 5. Mean weight gain over 3 d increased linearly from 42 to 95 g per bird with increasing extrusion temperatures of FFSB. Pancreatic enlargement was evident after 6 d of feeding with FFSB processed at lower temperatures, even when the TIA level was at the recommended threshold of 4 mg/g. 6. The results emphasise the importance of controlled conditions during processing of FFSB for poultry diets and suggest that processing of FFSB in order to reduce TIA levels below 4 mg/g may provide significant benefits for broiler chicks.


Asunto(s)
Alimentación Animal/análisis , Pollos/crecimiento & desarrollo , Grasas de la Dieta/farmacología , Glycine max/química , Valor Nutritivo , Inhibidores de Tripsina/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Relación Dosis-Respuesta a Droga , Manipulación de Alimentos , Calor , Masculino , Aumento de Peso
11.
Poult Sci ; 96(9): 3338-3350, 2017 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-28854758

RESUMEN

Four experiments were carried out to study the possible differences in metabolizable energy (ME) of meals (RSM) or expeller meals (RSE) from double-low rapeseed (Expt. 1), the influence of processing on ME (Expt. 2) and on relative phosphorus (P) bioavailability (Expt. 3) in RSM, and effect of RSM inclusion on growth performance of broilers (Expt. 4). For Expt. 1, diets with 300 g/kg RSM from 11 RSM and 4 RSE varieties were fed to broilers from d 14 to 21, with excreta collection on d 19 to 21. Each treatment had 8 replicates and 3 birds per replicate. Energy metabolizability of RSM of a specialized high glucosinolate variety (V275OL) was greater (P < 0.05) than all the other varieties. In Expt. 2, two RSM varieties were processed with mild or conventional processing condition. There were no variety effects on ME, but ME and MEn were greater (P < 0.01) for RSM processed by mild processing condition. In Expt. 3, P bioavailability of RSM was determined, relative to MSP, using growth performance and tibia ash as responses. Phosphorus relative bioavailability values were greater (P < 0.05) in RSM of DK Cabernet variety processed using the mild processing condition. In Expt. 4, two RSM varieties were added to wheat-soybean meal-based diet at the rates of 50, 100, 150, or 200 g/kg and fed to broilers from d 0 to 42. Inclusion of 150 and 200 g/kg of RSM resulted in reduced weight gain and increased feed conversion ratio (FCR) compared (P < 0.01) with the lower inclusion levels during the starter phase. For the entire trial (d 0 to 42), weight gain was greater (P < 0.01) for birds receiving diets with RSM from PR46W21 variety. It was concluded from the experiments that apart from the residual ether extract content, variety differences had no impact on ME of RSM, conventional processing reduced ME and relative bio-availability of P; and that the maximum level of RSM inclusion depends on maximum growth performance level desired.


Asunto(s)
Brassica napus/química , Pollos/crecimiento & desarrollo , Pollos/metabolismo , Valor Nutritivo , Fósforo/metabolismo , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales/efectos de los fármacos , Animales , Disponibilidad Biológica , Dieta/veterinaria , Suplementos Dietéticos/análisis , Metabolismo Energético/efectos de los fármacos , Masculino , Distribución Aleatoria
12.
J Vet Intern Med ; 20(5): 1207-11, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17063718

RESUMEN

Glycogen Branching Enzyme Deficiency (GBED), a fatal condition recently identified in fetuses and neonatal foals of the Quarter Horse and Paint Horse lineages, is caused by a nonsense mutation in codon 34 of the GBE1 gene, which prevents the synthesis of a functional GBE protein and severely disrupts glycogen metabolism. The aims of this project were to determine the mutant GBE1 allele frequency in random samples from the major relevant horse breeds, as well as the frequency with which GBED is associated with abortion and early neonatal death using the tissue archives from veterinary diagnostic laboratories. The mutant GBE1 allele frequency in registered Quarter Horse, Paint Horse, and Thoroughbred populations was 0.041, 0.036, and 0.000, respectively. Approximately 2.5% of fetal and early neonatal deaths in Quarter Horse-related breeds submitted to 2 different US diagnostic laboratories were homozygous for the mutant GBE1 allele, with the majority of these being abortions. Retrospective histopathology of the homozygotes detected periodic acid Schiff's (PAS)-positive inclusions in the cardiac or skeletal muscle, which is characteristic of GBED, in 8 out of the 9 cases. Pedigree and genotype analyses supported the hypothesis that GBED is inherited as a simple recessive trait from a single founder. The frequency with which GBED is associated with abortion and neonatal mortality in Quarter Horse-related breeds makes the DNA-based test valuable in determining specific diagnoses and designing matings that avoid conception of a GBED foal.


Asunto(s)
Enzima Ramificadora de 1,4-alfa-Glucano/deficiencia , Alelos , Enfermedad del Almacenamiento de Glucógeno Tipo IV/veterinaria , Enfermedades de los Caballos/enzimología , Enfermedades de los Caballos/genética , Enzima Ramificadora de 1,4-alfa-Glucano/genética , Aborto Veterinario/enzimología , Aborto Veterinario/genética , Aborto Veterinario/patología , Animales , Animales Recién Nacidos , ADN/química , ADN/genética , Femenino , Genotipo , Enfermedad del Almacenamiento de Glucógeno Tipo IV/enzimología , Enfermedad del Almacenamiento de Glucógeno Tipo IV/genética , Enfermedad del Almacenamiento de Glucógeno Tipo IV/patología , Histocitoquímica/veterinaria , Enfermedades de los Caballos/patología , Caballos , Músculo Esquelético/patología , Miocardio/patología , Linaje , Reacción en Cadena de la Polimerasa/veterinaria , Embarazo , Estudios Retrospectivos
13.
Biochim Biophys Acta ; 996(1-2): 89-94, 1989 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-2500154

RESUMEN

Relative values of Vmax/Km for hydrolysis of 40 peptide p-nitroanilides catalyzed by human Cl-s and human acrosin are reported. For Cl-s, Ac-Lys(gamma Cbz)-Gly-Arg is the optimum sequence, but 25% of the substrates have (Vmax/Km)rel greater than 0.25 compared to this sequence. The best acrosin substrate tested has the sequence Tos-Gly-Pro-Arg, although (Vmax/Km)rel greater than 0.15 for more than half of the substrates. Proline at P2 is preferred by acrosin. Both enzymes prefer arginine at P1 greater than or equal to 3-fold over lysine and will not accept citrulline. In addition, occupancy of site S3 may yield an increase in Vmax/Km of greater than or equal to 10-fold with either enzyme, but many residues are accepted at S2, S3 and S4. Thus, an acrosin assay using Tos-Gly-Pro-Arg p-nitroanilide as a substrate is more than 20-times as sensitive as existing assays with blocked arginine derivatives.


Asunto(s)
Acrosina/metabolismo , Anilidas/metabolismo , Enzimas Activadoras de Complemento/metabolismo , Complemento C1s/metabolismo , Péptidos/metabolismo , Serina Endopeptidasas/metabolismo , Arginina/metabolismo , Sitios de Unión , Citrulina/metabolismo , Humanos , Técnicas In Vitro , Cinética , Lisina/metabolismo , Especificidad por Sustrato
14.
Arch Intern Med ; 146(2): 268-71, 1986 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-3484940

RESUMEN

Total body scintiscans, serum alkaline phosphatase estimations, and serum osteocalcin radioimmunoassays were performed in 49 consecutive patients with Paget's disease of bone. Eleven were receiving calcitonin (salmon synthetic) at the time of the study. The serum alkaline phosphatase activities were elevated in all but one patient, with the highest value almost 50 times the upper limit of the reference range. Serum osteocalcin concentrations were elevated in 53% of patients and normal in the rest. The highest serum osteocalcin value was 4.2 times the upper limit of the reference range. The correlation coefficient between the extent of skeletal involvement and serum osteocalcin level was .70, while that between skeletal involvement and serum alkaline phosphatase level was .55. In spite of the better correlation between bone scintiscans and serum osteocalcin level, osteocalcin measurements are diagnostically less useful than serum alkaline phosphatase estimations in patients with Paget's disease of bone.


Asunto(s)
Proteínas de Unión al Calcio/sangre , Osteítis Deformante/sangre , Anciano , Fosfatasa Alcalina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteocalcina
15.
Int J Biochem Cell Biol ; 29(7): 1013-20, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9375381

RESUMEN

There is increasing evidence that some mRNAs are localised in eukaryotic somatic cells, but it is unclear what proportion of mRNAs are localised and whether this sorting involves 3'-untranslated sequences. The presence of a localisation signal within the 3'-untranslated region of vimentin mRNA was investigated by studying mRNA distribution in fibroblasts transfected with beta-globin and hybrid globin-vimentin gene constructs. In cells transfected with constructs containing either a fragment of the rabbit beta-globin gene containing both coding sequences and 3'untranslated region or the beta-globin coding sequences alone in situ hybridisation showed that beta-globin mRNA was distributed throughout the cytoplasm without any evident localisation. In contrast, in cells transfected with globin coding sequences linked to the vimentin 3'-untranslated region there was a strong perinuclear localisation of the hybrid mRNA. The results show that loss of its endogenous 3'-untranslated region does not affect distribution of beta-globin mRNA whereas the vimentin 3'-untranslated region causes an altered localisation of beta-globin mRNA. We conclude that the vimentin 3'-untranslated region contains a localisation signal which can direct reporter sequences to the perinuclear cytoplasm.


Asunto(s)
Compartimento Celular , ARN Mensajero/genética , Secuencias Reguladoras de Ácidos Nucleicos , Vimentina/genética , Células 3T3 , Animales , Globinas/genética , Humanos , Hibridación in Situ , Ratones , ARN Mensajero/metabolismo , Conejos , Proteínas Recombinantes de Fusión/genética , Transfección
16.
J Clin Endocrinol Metab ; 75(3): 886-9, 1992 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-1517381

RESUMEN

Twenty-one patients who underwent surgical treatment for thyrotoxicosis and who were found at operation to have thyroid cancer are presented. Sixteen had Graves' disease and 5 had toxic nodular goiter. The group with Graves' is compared with 110 euthyroid patients with thyroid cancer who underwent their initial surgery in the same time period and who were of the same age (+/- 1 yr) and sex as the patients with Graves' disease. None of the thyrotoxic patients died during follow-up of 2-24 yr or developed subsequent metastases. The 1 patient with a local lymph node metastasis has not shown evidence of recurrence. Hypoparathyroidism appeared as a complication in only 1 patient. The size of tumors in the patients with Graves' disease was significantly smaller than in the euthyroid group. The course of the disease in both the patients with Graves' disease and the thyrotoxic group as a whole was relatively benign. This series does not support the recent suggestions that thyroid cancer in patients with Graves' disease is more aggressive than in either patients with toxic nodular goiter or euthyroid subjects. Patients with Graves' disease and thyroid cancer should be treated identically to other patients with thyroid cancer. Therapy should consist of total thyroidectomy followed by a postoperative 131I scan. Residual tissue or metastases found on the scan should be ablated with 6 GBq 131I. The patient should receive a suppressive dose of T4.


Asunto(s)
Enfermedad de Graves/complicaciones , Neoplasias de la Tiroides/complicaciones , Tirotoxicosis/complicaciones , Adulto , Carcinoma Papilar/complicaciones , Carcinoma Papilar/patología , Terapia Combinada , Femenino , Enfermedad de Graves/cirugía , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Pronóstico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Tirotoxicosis/cirugía
17.
Curr Opin Drug Discov Devel ; 2(3): 234-8, 1999 May.
Artículo en Inglés | MEDLINE | ID: mdl-19649951

RESUMEN

Advances in molecular biology and genetics have furnished more targets than could be reasonably progressed, forcing the pharmaceutical industry to invest in increasing chemistry and screening throughput. Combinatorial chemistry, automation and miniaturization are described as the keys to success. Many pharmaceutical companies assisted by the vendor community have risen to the challenges, delivering more functional and reliable robotics; a number of recent developments are described. These, in turn, have highlighted other deficiencies, for example in target selection, integration and scheduling, and assay and reaction optimization. These areas provide the challenges for the future and have already sparked several new initiatives, a number of which are described.

18.
J Nucl Med ; 18(3): 274-5, 1977 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-839277

RESUMEN

An unusual cause for a positive liver-lung scan is presented. A cold area between the base of the right lung and the liver in a 78-year-old woman was reported as being due to a subphrenic abscess. This defect was subsequently found to be a right subphrenic kidney.


Asunto(s)
Hígado , Pulmón , Cintigrafía , Anciano , Anomalías Congénitas/diagnóstico , Femenino , Humanos , Riñón/anomalías
19.
Biochem Pharmacol ; 43(4): 845-53, 1992 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-1540238

RESUMEN

Previous studies of endothelin-1 (ET) synthesis have shown that some cultured endothelial cells secrete an intermediate product, big-endothelin-1 (bigET), suggesting that the processing of secreted bigET to ET may be physiologically significant. In this study, two pertinent ET converting enzyme activities, mast cell chymase I (EC 3.4.21.39) and a phosphoramidon-sensitive, neutral metalloprotease, were identified in a rat lung particulate fraction. We perfused rat lungs with bigET and chymostatin or phosphoramidon to study the relevance of these two proteases to the processing of extracellular bigET in vivo. Addition of compound 48/80 (a compound which activates mast cells, causing degranulation and release of chymase) to the perfusion buffer greatly increased hydrolysis of exogenously added bigET to ET. ET formation was inhibited completely by 32 microM chymostatin, whereas inhibition by 50 microM phosphoramidon was incomplete and variable. Perfusate histamine levels were used to monitor the extent of mast cell degranulation, and inhibition of ET production by phosphoramidon was attributed to inhibition of degranulation, per se. There was a direct correlation between perfusate ET and histamine levels in both control and phosphoramidon-treated (but not chymostatin-treated) lungs. Our results suggest that chymase from lung mast cells is capable of physiologically relevant extracellular processing by bigET to ET in the perfused rat lung.


Asunto(s)
Endotelinas/metabolismo , Pulmón/enzimología , Mastocitos/enzimología , Precursores de Proteínas/metabolismo , Serina Endopeptidasas/metabolismo , Animales , Ácido Aspártico Endopeptidasas/antagonistas & inhibidores , Quimasas , Endotelina-1 , Enzimas Convertidoras de Endotelina , Endotelinas/antagonistas & inhibidores , Glicopéptidos/farmacología , Concentración de Iones de Hidrógeno , Metaloendopeptidasas , Oligopéptidos , Perfusión , Precursores de Proteínas/antagonistas & inhibidores , Ratas , Ratas Endogámicas
20.
J Steroid Biochem Mol Biol ; 42(3-4): 375-81, 1992 May.
Artículo en Inglés | MEDLINE | ID: mdl-1606048

RESUMEN

Metabolism of 11-deoxycorticosterone (DOC) by hamster adrenal mitochondria gives 19-hydroxy-DOC and corticosterone (via 11-hydroxylation) in approximately equal yields. The ratio of 19- to 11-hydroxylation was invariant with changes in concentration of substrate or a competitive inhibitor. It is most likely, therefore, that a single 11,19-hydroxylase catalyzes both oxidations. Both primary products are further oxidized to the corresponding carbonyl analogs, 19-oxo-DOC and 11-dehydrocorticosterone, at rates that are approx. 20% of their rates of formation. The oxidation of 11-dehydrocorticosterone is catalyzed by a dehydrogenase utilizing either NAD or NADP while the oxidation of 19-hydroxy-DOC is catalyzed by an oxidase requiring NADPH. The 11-dehydrocorticosterone is stable in this enzyme preparation while 19-oxo-DOC is metabolized to two additional products, which are tentatively identified as 19-oic-DOC and 19-norcorticosterone. 19-nor-DOC was found to be hydroxylated at a rate that is 20% faster than the rate for DOC under the same conditions. It is therefore possible that 19-norcorticosterone can arise from 19-oic-DOC via decarboxylation to 19-nor-DOC and subsequent 11-hydroxylation, but the kinetics of its formation suggest that it may actually be formed directly from 19-oxo-DOC without free intermediates. 4-Androstene-3,17-dione and 17-hydroxy-DOC were also substrates for this 11,19-hydroxylase, but 18-hydroxy-DOC was not. Maintenance of hamsters on a low sodium diet had no effect on the metabolism of DOC by the isolated adrenal mitochondria.


Asunto(s)
Glándulas Suprarrenales/metabolismo , Desoxicorticosterona/metabolismo , Animales , Cricetinae , Mesocricetus , Mitocondrias/metabolismo , Oxidación-Reducción , Factores de Tiempo
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