RESUMO
Gaucher disease is the most frequent lysosome storage disease and presents an autosomal recessive mode of inheritance. It is caused by mutations at the GBA gene leading to deficient activity of the glucocerebrosidase enzyme. This report describes 12 new mutations [c.38A>G (K-27R), c.220G>A (G35S), c.448G>A (E111K), IVS4+1G>A, c.746C>T (A210V), c.776A>G (Y220C), c.793delC (Q226_fs4X), c.1102C>T (R329C), c.1300C>T (R395C), c.1309G>A (V398I), c.1324-1326delATT (delI403) and c.1583T>C (I489T)] and 4 novel silent alterations [c.342C>T (F75), c.528C>T (D137), c.1011C>T (D298) and c.1092G>A (G325)] detected among 40 unrelated Brazilian type 1 Gaucher disease patients by a combination of RFLP, dHPLC and DNA sequencing procedures. The R329C mutation, previously described in a Parkinson's disease patient (A. Lwin, E. Orvisky, O. Goker-Alpan, M.E. LaMarca, E. Sidransky. Glucocerebrosidase mutations in subjects with Parkinsonism. Mol. Genet. Metab. 81 (2004) 70-73), is described here for the first time in a Gaucher disease patient. Several genotype-phenotype correlations could be established, contributing significantly to the panel of reported mutations and conferring predictive value to their detection.
Assuntos
Doença de Gaucher/genética , Glucosilceramidase/genética , Mutação de Sentido Incorreto , Polimorfismo de Fragmento de Restrição , Brasil , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Masculino , Transtornos Parkinsonianos/genética , Reação em Cadeia da PolimeraseRESUMO
Gaucher disease (GD), the most prevalent lysosome storage disorder, presents an autosomal recessive mode of inheritance. It is a paradigm for therapeutic intervention in medical genetics due to the existence of effective enzyme replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian patients, carried out in order to establish the frequency of the most common mutations and to provide prognostic information based on genotype-phenotype correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47% of all the alleles, but N370S/N370S homozygosity was found in only 10% of the patients, a much lower frequency than expected, suggesting that most individuals presenting this genotype may not receive medical attention. Recombinant alleles were detected at a high frequency: 44% of the chromosomes bearing mutation L444P had other mutations derived from the pseudogene sequence, present in 25% of patients. Three neuronopathic type 2 patients were homozygous for L444P, all presenting additional mutations (E326K or recombinant alleles) that probably lead to the more severe phenotypes. Six children, classified as type 1 GD patients, had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest later in life. This would indicate the need for a higher treatment dose during enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous type 1 patients and also in compound heterozygosity in 5 (42%) type 3 patients. These findings indicate that G377S cannot be unambiguously classified as mild and suggest an allele-dose effect for this mutation.
Assuntos
Alelos , Doença de Gaucher/genética , Mutação/genética , Análise Mutacional de DNA , Doença de Gaucher/diagnóstico , Testes Genéticos , Genótipo , Humanos , Mucosa Bucal , Fenótipo , Polimorfismo de Fragmento de Restrição , Recombinação GenéticaRESUMO
Gaucher disease (GD), the most prevalent lysosome storage disorder, presents an autosomal recessive mode of inheritance. It is a paradigm for therapeutic intervention in medical genetics due to the existence of effective enzyme replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian patients, carried out in order to establish the frequency of the most common mutations and to provide prognostic information based on genotype-phenotype correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47 percent of all the alleles, but N370S/N370S homozygosity was found in only 10 percent of the patients, a much lower frequency than expected, suggesting that most individuals presenting this genotype may not receive medical attention. Recombinant alleles were detected at a high frequency: 44 percent of the chromosomes bearing mutation L444P had other mutations derived from the pseudogene sequence, present in 25 percent of patients. Three neuronopathic type 2 patients were homozygous for L444P, all presenting additional mutations (E326K or recombinant alleles) that probably lead to the more severe phenotypes. Six children, classified as type 1 GD patients, had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest later in life. This would indicate the need for a higher treatment dose during enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous type 1 patients and also in compound heterozygosity in 5 (42 percent) type 3 patients. These findings indicate that G377S cannot be unambiguously classified as mild and suggest an allele-dose effect for this mutation.
Assuntos
Humanos , Alelos , Análise Mutacional de DNA , Doença de Gaucher/genética , Mutação/genética , Testes Genéticos , Genótipo , Doença de Gaucher/diagnóstico , Mucosa Bucal , Fenótipo , Polimorfismo de Fragmento de Restrição , Recombinação GenéticaRESUMO
Our objectives were to evaluate strategies to improve productivity and economic returns from beef and dual-purpose cattle systems based on data collected on one dual-purpose (Bos taurus x Bos indicus) and two beef (Nellore) cattle farms in the western Amazon region of Brazil. Forage chemical composition and digestion rates of carbohydrate fractions of grazed Brachiaria decumbens and Brachiaria brizantha cv. Marandu grasses and Pueraria phaseoloides (tropical kudzu) legume were measured monthly during a 9-mo period from the end of one dry season to the end of the subsequent rainy season. Measurements of milk and growth responses to grazing these forages were used to predict animal productivity responses to dietary nutrient availability throughout an annual cycle. The ME available for gain in our simulations was always more limiting than metabolizable protein. The predicted ME available for gain was 0.50 kg/d for steers grazing B. brizantha and 0.40 kg/d for finishing steers grazing B. decumbens. Grasses contained more NDF and neutral detergent insoluble protein and less ME (P < 0.05) in the rainiest months than in the less rainy season, which resulted in 20% less predicted weight gain by growing steers (P < 0.05). Supplementation with sorghum grain was required to increase milk production and growth by 25 or 50% per animal, respectively, but this strategy was less profitable than current forage-only diets. Greater productivity of land and labor from higher stocking indicated greater net margins for beef production, but not for milk. This study suggested that more intensive beef production by judicious fertilization of grass-legume pastures and greater stocking density is the preferable strategy for owners of these cattle systems to improve economic returns under current conditions. It also might help decrease the motivation for additional forest clearing.
Assuntos
Ração Animal/normas , Criação de Animais Domésticos/economia , Criação de Animais Domésticos/métodos , Bovinos/crescimento & desenvolvimento , Leite/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Brasil , Bovinos/fisiologia , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/metabolismo , Fibras na Dieta/administração & dosagem , Fibras na Dieta/metabolismo , Proteínas Alimentares/administração & dosagem , Proteínas Alimentares/metabolismo , Digestão , Feminino , Lactação , Masculino , Valor Nutritivo , Poaceae/química , Densidade Demográfica , Pueraria/química , Estações do Ano , Clima Tropical , Aumento de PesoRESUMO
Two experiments using the Cornell Net Carbohydrate and Protein System were conducted to characterize the carbohydrate and protein fractions and corresponding rates of digestion of 15 tropical pasture grasses and to evaluate their ability to support milk production by dual-purpose cows. In the first experiment, ranges in carbohydrate and protein fractions of 15 grasses at 35 to 42 d of regrowth were: neutral detergent fiber (NDF) 63.5 to 74.9% of DM; permanganate lignin 4.7 to 7.8% of NDF; CP 5.5 to 11.9% of DM; and soluble protein 15.1 to 44.1% of crude protein (CP). The ranges of rates of digestion expressed as percent per hour were neutral detergent solubles (7.5 to 27.4); NDF (3.8 to 8.4); and neutral detergent insoluble protein (2.9 to 9.5). Predictions of the amount of milk that could be produced based on the amount of metabolizable energy supplied by the diet decreased 35% when NDF increased from 60 to 80%, and increased 88% when the rate of digestion of NDF increased from 3 to 6%/h. The milk production that could be sustained based on metabolizable protein in the diet doubled as CP increased from 4 to 12%. In the second experiment, nitrogen fertilization reduced NDF 7.3% and increased CP 84% without changing protein solubility, resulting in increased rumen nitrogen and metabolizable protein balances. With all forages, the Cornell Net Carbohydrate and Protein System predicted that availability of metabolizable protein would limit milk production. Predicted microbial growth was limited by ruminally available protein rather than by available carbohydrate.
Assuntos
Bovinos/fisiologia , Lactação , Poaceae , Animais , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/análise , Carboidratos da Dieta/metabolismo , Fibras na Dieta/administração & dosagem , Fibras na Dieta/análise , Proteínas Alimentares/administração & dosagem , Proteínas Alimentares/análise , Proteínas Alimentares/metabolismo , Digestão , Ingestão de Energia , Feminino , Fertilizantes , Lignina/administração & dosagem , México , Nitrogênio , Poaceae/química , Clima TropicalRESUMO
Objectives of this study were to compare three nutritional management strategies for dual-purpose herds in Venezuela in 1987 using a deterministic, multiperiod linear programming model of a representative farm. The model maximized discounted net margin (total revenues minus variable costs) from the herd for a 3-yr cow replacement cycle partitioned into six periods. The periods accounted for seasonal variation in forage availability and quality, and the model provided information about optimal animal inventories, animal sales, land in forage, and feed supplements. We compared current nutritional management practices and alternatives allowing optimal supplementation with commercial concentrate, molasses, cassava root, and urea. Iteration between the programming model and results from the Cornell Net Carbohydrate and Protein System assured technical coefficients consistent with predicted animal performance. Compared with management practices relying on commercial concentrate, optimal use of molasses and urea permitted increases in the stocking rate. Productivity and profit were restricted primarily by energy intake, which was constrained by intakes of NDF and DM. Alternative management strategies changed the relative importance of nutrient requirements and feed intake constraints. Thus, optimal interventions to alleviate nutritional constraints will vary with current management. Mobilizing adipose and protein tissues during lactation was optimal for most strategies. Supplementing with molasses and urea instead of commercial concentrate was the most profitable strategy, increasing herd net margin by 16% compared to the predominant feeding strategy in the late 1980s.
Assuntos
Criação de Animais Domésticos/métodos , Fenômenos Fisiológicos da Nutrição Animal , Bovinos/fisiologia , Carne/economia , Leite/economia , Tecido Adiposo/metabolismo , Ração Animal/economia , Criação de Animais Domésticos/economia , Animais , Composição Corporal/fisiologia , Bovinos/crescimento & desenvolvimento , Indústria de Laticínios/economia , Dieta/economia , Fibras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Feminino , Lactação/fisiologia , Modelos Lineares , Masculino , Proteínas/metabolismo , Chuva , Estações do Ano , VenezuelaRESUMO
Increasingly, medical teams are providing sophisticated surgical treatment to pediatric patients in developing nations. Such care is often administered under relatively austere conditions using easily transported equipment. Because some of these patients may present with congenital or acquired airway abnormalities that make direct laryngoscopy difficult or impossible, alternative methods of endotracheal intubation should be available. One such technique is lightwand-guided endotracheal intubation. Use of the lightwand has a proven record of success and obviates the need for the heavier, more delicate, and more expensive flexible fiber-optic laryngoscope or pediatric bronchoscope. Two cases are reported in which pediatric patients with difficult airway anatomy due to severe burn scar contractures were successfully and easily intubated using the lightwand. This technique is useful for management of the difficult pediatric airway in the austere environment of the typical medical relief mission.