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1.
Poult Sci ; 98(11): 5820-5830, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31392330

RESUMO

The addition of fiber in chick feeds is known to dilute nutrients; as a result, this may reduce nutrient digestibility and performance. However, recent studies suggest that moderate inclusion of insoluble fibers (2 to 3%) may stimulate gizzard development, which could result in better nutrient utilization and chick growth. The previous fiber sources evaluated were subject to wide fluctuation in their nutritional and chemical composition due to variation in processing. Miscanthus giganteus is a C4 grass purposefully grown for its fiber content which has a consistent fiber composition compared to food process residues. The objectives of this study were to determine the effect of dietary fiber source and particle size on day-old chick performance and nutrient digestibility. Day-old chicks (8 chicks per cage, 5 cages per treatment) were fed diets containing 3% of either sepiolite (SEP), cellulose (CEL), coarse beet pulp (BP), fine BP, coarse Miscanthus grass (MG), and fine MG. At the end of days 7, 14, and 21, chicks and experimental diets were weighed to compute average daily gain and feed intake. In addition, excreta from the previous 48 h of each data capture point was collected to determine nutrient digestibility. In general, chicks fed diets containing fiber consumed more feed, gained more weight, and had better feed conversion rate than birds fed the SEP diet. Particle size of the fiber had no effect on chick performance; however, nutrient utilization was higher (P < 0.05) for chicks fed coarse fiber particles compared to these fed fine fiber particles. Birds fed diets containing MG performed similar to chicks fed CEL (P > 0.05), but digestibility coefficients of birds fed BP diets were generally higher than chicks fed MG diets. In conclusion, chicks performed better with fiber in their diet and MG was comparable to CEL.


Assuntos
Galinhas/fisiologia , Fibras na Dieta/metabolismo , Digestão/efeitos dos fármacos , Nutrientes/fisiologia , Tamanho da Partícula , Poaceae/química , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Beta vulgaris/química , Celulose/administração & dosagem , Celulose/metabolismo , Dieta/veterinária , Fibras na Dieta/administração & dosagem , Fibras na Dieta/classificação , Silicatos de Magnésio/administração & dosagem , Silicatos de Magnésio/metabolismo , Masculino , Distribuição Aleatória
2.
Poult Sci ; 98(3): 1371-1378, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30351365

RESUMO

New protein ingredients are used to support pet food market growth and the development of new products while maintaining animal dietary needs. However, novel protein sources (e.g., spray-dried chicken, and (or) rice, pea, and potato protein concentrates) have limited data available regarding their protein quality. The objective of this study was to evaluate protein ingredients used in the pet food industry by laboratory analysis and a chick growth assay as a model. Following analysis for proximate and amino acid composition, chicks (six birds per pen with four pens per treatment) were fed experimental diets for 10 d. Diets contained 10% crude protein from each of the experimental protein sources (spray-dried egg-SDEG; spray-dried egg white-SDEW, spray-dried inedible whole egg-SDIE, chicken by-product meal-CBPM, chicken meal-CKML, low-temperature fluid bed air-dried chicken-LTCK, low-temperature and pressure fluid bed dried chicken-LTPC, spray-dried chicken-SDCK, whey protein concentrate-WPCT, corn gluten meal-CGML, corn protein concentrate-CPCT, potato protein isolate-PPIS, rice protein concentrate-RPCT, pea protein isolate-PEPI, soy protein isolate-SPIS, and soybean meal-SBML) along with an N-free diet (negative control). Chicks fed SDEG, SDIE, and LTPC had the highest protein efficiency ratio (PER; P < 0.0001; 5.18, 5.37, and 5.33, respectively), LTCK and SDCK were intermediate (4.54 and 4.79), and the CBPM and CKML were the lowest among the poultry proteins for EAA:NEAA, PER, and Lys availability. Among the vegetable proteins, PPIS and SBML had the highest PER values (3.60 and 3.48, P < 0.0001). In general, the chick PER method ranked the quality of animal protein sources higher than vegetable proteins, and these results were consistent with the EAA:NEAA ratio and Lys availability.


Assuntos
Aminoácidos/análise , Ração Animal/análise , Proteínas Alimentares/metabolismo , Proteínas Alimentares/normas , Fenômenos Fisiológicos da Nutrição Animal , Animais , Galinhas/metabolismo , Dieta/veterinária , Proteínas Alimentares/administração & dosagem , Proteínas do Ovo/análise , Valor Nutritivo , Proteínas de Plantas/análise , Produtos Avícolas/análise , Proteínas do Soro do Leite/análise
3.
BMC Med ; 16(1): 101, 2018 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-29961422

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a worldwide prevalence of 1-2%. In low-resource environments, in particular, early identification and diagnosis is a significant challenge. Therefore, there is a great demand for 'language-free, culturally fair' low-cost screening tools for ASD that do not require highly trained professionals. Electroencephalography (EEG) has seen growing interest as an investigational tool for biomarker development in ASD and neurodevelopmental disorders. One of the key challenges is the identification of appropriate multivariate, next-generation analytical methodologies that can characterise the complex, nonlinear dynamics of neural networks in the brain, mindful of technical and demographic confounders that may influence biomarker findings. The aim of this study was to evaluate the robustness of recurrence quantification analysis (RQA) as a potential biomarker for ASD using a systematic methodological exploration of a range of potential technical and demographic confounders. METHODS: RQA feature extraction was performed on continuous 5-second segments of resting state EEG (rsEEG) data and linear and nonlinear classifiers were tested. Data analysis progressed from a full sample of 16 ASD and 46 typically developing (TD) individuals (age 0-18 years, 4802 EEG segments), to a subsample of 16 ASD and 19 TD children (age 0-6 years, 1874 segments), to an age-matched sample of 7 ASD and 7 TD children (age 2-6 years, 666 segments) to prevent sample bias and to avoid misinterpretation of the classification results attributable to technical and demographic confounders. A clinical scenario of diagnosing an unseen subject was simulated using a leave-one-subject-out classification approach. RESULTS: In the age-matched sample, leave-one-subject-out classification with a nonlinear support vector machine classifier showed 92.9% accuracy, 100% sensitivity and 85.7% specificity in differentiating ASD from TD. Age, sex, intellectual ability and the number of training and test segments per group were identified as possible demographic and technical confounders. Consistent repeatability, i.e. the correct identification of all segments per subject, was found to be a challenge. CONCLUSIONS: RQA of rsEEG was an accurate classifier of ASD in an age-matched sample, suggesting the potential of this approach for global screening in ASD. However, this study also showed experimentally how a range of technical challenges and demographic confounders can skew results, and highlights the importance of probing for these in future studies. We recommend validation of this methodology in a large and well-matched sample of infants and children, preferably in a low- and middle-income setting.


Assuntos
Transtorno do Espectro Autista/diagnóstico por imagem , Biomarcadores/química , Eletroencefalografia/métodos , Adolescente , Transtorno do Espectro Autista/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
4.
J Nerv Ment Dis ; 203(11): 876-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26513510

RESUMO

Bereavement and its consequent grief are frequent in senior residential settings. Failure to manage grief appropriately can have serious medical consequences, principally clinical depression. Focused talk with a grieving person can help ease the pain of grief; it can also help prevent complications that often lead to depression. Along with mental health professionals, staff members and volunteers can be important, and less expensive, participants in reaching this goal.


Assuntos
Luto , Depressão/psicologia , Depressão/terapia , Instituição de Longa Permanência para Idosos , Idoso , Depressão/diagnóstico , Pesar , Humanos
5.
J Clin Microbiol ; 53(1): 52-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25339396

RESUMO

The effective management of women with human papillomavirus (HPV)-positive, cytology-negative results is critical to the introduction of HPV testing into cervical screening. HPV typing has been recommended for colposcopy triage, but it is not clear which combinations of high-risk HPV types provide clinically useful information. This study included 18,810 women with Hybrid Capture 2 (HC2)-positive, cytology-negative results and who were age ≥30 years from Kaiser Permanente Northern California. The median follow-up was 475 days (interquartile range [IQR], 0 to 1,077 days; maximum, 2,217 days). The baseline specimens from 482 cases of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) and 3,517 random HC2-positive noncases were genotyped using 2 PCR-based methods. Using the case-control sampling fractions, the 3-year cumulative risks of CIN3+ were calculated for each individual high-risk HPV type. The 3-year cumulative risk of CIN3+ among all women with HC2-positive, cytology-negative results was 4.6%. HPV16 status conferred the greatest type-specific risk stratification; women with HC2-positive/HPV16-positive results had a 10.6% risk of CIN3+, while women with HC-2 positive/HPV16-negative results had a much lower risk of 2.4%. The next most informative HPV types and their risks in HPV-positive women were HPV33 (5.9%) and HPV18 (5.9%). With regard to the etiologic fraction, 20 of 71 cases of cervical adenocarcinoma in situ (AIS) and adenocarcinoma in the cohort were positive for HPV18. HPV16 genotyping provides risk stratification useful for guiding clinical management; the risk among HPV16-positive women clearly exceeds the U.S. consensus risk threshold for immediate colposcopy referral. HPV18 is of particular interest because of its association with difficult-to-detect glandular lesions. There is a less clear clinical value of distinguishing the other high-risk HPV types.


Assuntos
Colo do Útero/virologia , Genótipo , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Colposcopia , Detecção Precoce de Câncer , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Tipagem Molecular , Teste de Papanicolaou , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/etiologia
6.
Eur J Appl Physiol ; 114(2): 375-84, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24318656

RESUMO

PURPOSE: To assess the efficacy of neck cooling on cognitive performance following exertional hyperthermia. METHODS: Twelve healthy men completed two experimental trials [control (CON) and neck cooling collar (NCC)] in a counter-balanced design. They ran on a treadmill at 70% VO2peak under warm and humid conditions (dry bulb temperature: 30.2 ± 0.3 °C, relative humidity: 71 ± 2 %) for 75 min or until volitional exhaustion. Gastrointestinal, neck and skin temperatures, heart rate and subjective ratings were assessed. Serum brain-derived neurotrophic factor (BDNF) levels were measured before and after each run. Cognitive performance comprising symbol digit matching, search and memory, digit span, choice reaction time and psychomotor vigilance test (PVT) were assessed before and after exercise. RESULTS: Mean gastrointestinal temperature was similar after exercise between trials (CON: 39.5 ± 0.4 °C vs. NCC: 39.6 ± 0.3 °C; p = 0.15). Mean neck temperature was lowered in NCC compared to CON after the run (36.4 ± 1.6 °C vs. NCC: 26.0 ± 0.3 °C; p < 0.001). Exercise-induced hyperthermia improved mean reaction time in the symbol digit matching test (-134 ± 154 ms; p < 0.05) and the PVT (-18 ± 30 ms; p < 0.05). Maximum span was increased in the digit span test (1 ± 2; p < 0.05). Application of NCC reduced the number of search errors made in level 3 of the search and memory test (p < 0.05). Mean serum BDNF levels were increased following exercise-induced hyperthermia in both trials (p < 0.05). CONCLUSION: Exercise-induced hyperthermia improves working memory and alertness. Neck cooling may only enhance performance in tasks of higher complexity.


Assuntos
Temperatura Corporal , Cognição , Exercício Físico , Hipotermia Induzida , Pescoço/fisiologia , Adulto , Fator Neurotrófico Derivado do Encéfalo/sangue , Estudos de Casos e Controles , Frequência Cardíaca , Humanos , Hipertermia Induzida , Masculino , Memória , Consumo de Oxigênio , Desempenho Psicomotor
7.
J Hazard Mater ; 157(1): 94-105, 2008 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-18258357

RESUMO

In part 1 of this paper, factors that influence hazards and eco/toxicity in composite hazardous wastes were described. In part 2, a computer-aided decision support tool based on fuzzy set theory is proposed to support the classification of composite wastes. Given the chemical properties, the nature of microorganisms that may be present, the behaviour of chemicals in humans and ecosystems, and the quantities of wastes, the computer-aided tool automatically classifies the waste as benign, partially hazardous, hazardous or highly hazardous. The functionality of the computer-aided decision tool is demonstrated through nine worked examples and the results are discussed in detail.


Assuntos
Técnicas de Apoio para a Decisão , Lógica Fuzzy , Resíduos Perigosos/efeitos adversos , Resíduos Perigosos/classificação , Algoritmos , Animais , Exposição Ambiental , Humanos
8.
Bioresour Technol ; 99(13): 5595-601, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18096382

RESUMO

A typical lignocellulosic agricultural residue, namely tobacco dust, was investigated for its heavy metal binding efficiency. The tobacco dust exhibited a strong capacity for heavy metals, such as Pb(II), Cu(II), Cd(II), Zn(II) and Ni(II), with respective equilibrium loadings of 39.6, 36.0, 29.6, 25.1 and 24.5mg of metal per g of sorbent. Moreover, the heavy metals loaded onto the biosorbent could be released easily with a dilute HCl solution. Zeta potential and surface acidity measurements showed that the tobacco dust was negatively charged over a wide pH range (pH>2), with a strong surface acidity and a high OH(-) adsorption capacity. Changes in the surface morphology of the tobacco dust as visualized by atomic force microscopy suggested that the sorption of heavy metal ions on the tobacco could be associated with changes in the surface properties of the dust particles. These surface changes appeared to have resulted from a loss of some of the structures on the surface of the particles, owing to leaching in the acid metal ion solution. However, Fourier transform infrared spectroscopy (FTIR) showed no substantial change in the chemical structure of the tobacco dust subjected to biosorption. The heavy metal uptake by the tobacco dust may be interpreted as metal-H ion exchange or metal ion surface complexation adsorption or both.


Assuntos
Metais Pesados/isolamento & purificação , Nicotiana , Adsorção , Cálcio/análise , Cinética , Lignina/análise , Magnésio/análise , Soluções , Volatilização , Gerenciamento de Resíduos/métodos
9.
J Hazard Mater ; 154(1-3): 1040-51, 2008 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-18082951

RESUMO

In the literature on hazardous waste classification, the criteria used are mostly based on physical properties, such as quantity (weight), form (solids, liquid, aqueous or gaseous), the type of processes generating them, or a set of predefined lists. Such classification criteria are inherently inadequate to account for the influence of toxic and hazard characteristics of the constituent chemicals in the wastes, as well as their exposure potency in multimedia environments, terrestrial mammals and other biota. Second, none of these algorithms in the literature has explicitly presented waste classification by examining the contribution of individual constituent components of the composite wastes. In this two-part paper, we propose a new automated algorithm for waste classification that takes into account physicochemical and toxicity effects of the constituent chemicals to humans and ecosystems, in addition, to the exposure potency and waste quantity. In part I, available data on the physicochemical and toxicity properties of individual chemicals in humans and ecosystems, their exposure potency in environmental systems and the effect of waste quantity are described, because they fundamentally contribute to the final waste ranking. Knowledge acquisition in this study was accomplished through the extensive review of published and specialized literature to establish facts necessary for the development of fuzzy rule-bases. Owing to the uncertainty and imprecision of various forms of data (both quantitative and qualitative) essential for waste classification, and the complexity resulting from knowledge incompleteness, the use of fuzzy set theory for the aggregation and computation of waste classification ranking index is proposed. A computer-aided intelligent decision tool is described in part II of this paper and the functionality of the fuzzy waste classification algorithm is illustrated through nine worked examples.


Assuntos
Técnicas de Apoio para a Decisão , Lógica Fuzzy , Resíduos Perigosos/classificação , Algoritmos , Animais , Exposição Ambiental , Resíduos Perigosos/efeitos adversos , Humanos
10.
J Hazard Mater ; 137(2): 723-33, 2006 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-16701941

RESUMO

In this paper, a fuzzy waste index for evaluating the hazard posed by composite wastes generated from industrial processes is proposed. Within this methodology, a fuzzy index as a measure of hazardousness of a given composite waste is derived from the crisp inputs of its component's flammability, corrosivity, toxicity and reactivity attributes based on the National Fire Protection Association (NFPA) hazard rankings. The novelty of this work lies in establishing an integrated fuzzy hazardous waste index (FHWI) which provides a single-value representing the hazard ranking of a composite waste. This is contrary to current techniques which do not provide a final aggregated hazard index. The efficacy of the new proposed approach is illustrated through several worked examples. The results demonstrate that the fuzzy algorithm can be useful in aiding policy and decision-makers in conducting comprehensive initial evaluation of the status of waste hazardous status without the need for costly laboratory experiments. As such, the approach offers a robust and transparent decision-making methodology.


Assuntos
Lógica Fuzzy , Resíduos Perigosos , Algoritmos , Resíduos Perigosos/classificação , Medição de Risco , Incerteza
11.
J Nutr Biochem ; 14(1): 24-31, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12559474

RESUMO

Dietary oxidized lipids can increase oxidative stress and potentially contribute to a variety of disease syndromes. This research describes the first use of a canine model to assess the effects of dietary oxidized lipids on growth, antioxidant status, and some immune functions. Three groups of eight, two-month old coon-hound puppies were pair fed diets for 16 weeks. The control diet contained <50 ppm aldehydes, and two additional diets contained thermally oxidized lipids targeted to contain 100 ppm aldehydes (medium-oxidation) and 500 ppm aldehydes (high-oxidation). Dogs fed the high-oxidation diet weighed less than those from the medium-oxidation (P < 0.05) and control groups (P < 0.001) at the end of the study. Oxidized lipids reduced serum vitamin E levels, total body fat content, and bone appositional rate. At different time points of the study, peripheral blood neutrophils and monocytes from dogs fed the HO diet had reduced oxidative burst capacity and produced less superoxide and hydrogen peroxide when stimulated with phorbol esters compared to the control group. Lymphocyte blastogenesis in response to concanavalin A was suppressed by dietary oxidized lipid. This study indicates that dietary oxidized lipids negatively affect the growth, antioxidant status, and some immune functions of dogs. Importantly, some effects are evident at 100 ppm aldehydes in the diet, which is a moderate level of oxidation. The rapid growth and weight gain of the dog during the first 6 months of life may also provide a better model for assessing the risks of dietary oxidized lipid in children and adolescents than previously used rodent models.


Assuntos
Crescimento/efeitos dos fármacos , Sistema Imunitário/efeitos dos fármacos , Lipídeos/efeitos adversos , Osteogênese/efeitos dos fármacos , Aldeídos/análise , Animais , Composição Corporal/efeitos dos fármacos , Dieta , Dinoprostona/biossíntese , Cães , Ácidos Graxos/análise , Peroxidação de Lipídeos , Ativação Linfocitária/efeitos dos fármacos , Explosão Respiratória/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacos
13.
J Anim Sci ; 80(9): 2493-501, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12350027

RESUMO

Five Holstein steers (450 kg) with cannulas in the rumen, proximal duodenum, and terminal ileum were used in a 5 x 5 Latin square design to study the effects of extrusion temperature on site of digestion of nitrogenous compounds in whole soybeans. The basal diet contained 50% corn silage, 24% alfalfa hay, 16.6% corn starch, 4.05% ground corn, 1% urea, and 3.4% soybean oil. Raw soybeans or soybeans extruded at 116, 138, or 160 degrees C (diets 116, 138, and 160, respectively) replaced the soybean oil and most of the corn starch in the test diets. Total N (g/d) reaching the duodenum was 232, 293, 285, 308, and 299 for the basal, raw, 116, 138, and 160 diets, respectively. No differences were observed between the raw and extruded soybeans (P = 0.81), or for the linear or quadratic effects of extrusion temperature (P = 0.56 and P = 0.45, respectively). Nonbacterial N (g/d) reaching the duodenum was 63.1, 104.6, 106.7, 101.9, and 113.9 for the same diets, respectively, and was not influenced by extrusion or extrusion temperature. Nitrogen disappearance from the small intestine (g/d) was 150 for the basal diet, 194 for the raw soybean diet, and 187,221, and 213 for the 116,138, and 160 degrees C extruded diets, respectively; no differences were observed between the raw and the extruded soybeans, or for diets containing soybeans extruded at different temperatures. Nitrogen disappearance (% of N entering) from the small intestine was lower (P < 0.05) for steers fed the basal diet than for steers fed the soybean-supplemented diets (64.1 vs 68.5%). No differences (P > 0.10) due to extrusion temperature were detected for flows of individual, essential AA, nonessential AA, and total AA at the duodenum. As extrusion temperatures increased, there were linear increases (P < 0.10) in disappearance (g/d) of all individual AA from the small intestine except for methionine and glycine. Essential, nonessential, and total AA disappearance from the small intestine were increased linearly (P < 0.10) with increasing extrusion temperature. Extrusion of soybeans can protect soy protein against extensive ruminal degradation without compromising intestinal digestibility.


Assuntos
Aminoácidos/metabolismo , Bovinos/metabolismo , Proteínas Alimentares/metabolismo , Digestão , Manipulação de Alimentos/métodos , Glycine max , Ração Animal , Animais , Duodeno/metabolismo , Duodeno/fisiologia , Íleo/metabolismo , Íleo/fisiologia , Masculino , Nitrogênio/metabolismo , Rúmen/metabolismo , Rúmen/microbiologia , Rúmen/fisiologia , Temperatura
14.
Mol Hum Reprod ; 7(12): 1167-72, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11719594

RESUMO

HLA-G is a non-classical human leukocyte antigen expressed primarily in fetal tissues at the maternal-fetal interface. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. To evaluate the role of polymorphisms at this locus in maternal-fetal interactions, 113 couples with unexplained recurrent miscarriage were genotyped for seven polymorphisms that define 12 HLA-G alleles. Logistic regression analysis was used to assess whether HLA-G genotypes were associated with an increased risk for a subsequent miscarriage. The presence of an HLA-G*0104 or HLA-G*0105N allele in either partner was significantly associated with an increased risk for miscarriage, after adjustment for maternal age, number of previous miscarriages, history of a previous liveborn, and treatment with paternal mononuclear cells. The *0104 and *0105N alleles are defined by polymorphisms in the alpha-2 domain and encode protein variants that are present only in the full-length HLA-G1 protein. The significant genotype-specific risk in this population suggests that allelic variation in the alpha-2 domain of the HLA-G1 isoforms contributes to recurrent miscarriage.


Assuntos
Aborto Habitual/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Polimorfismo Genético , Gravidez , Aborto Habitual/imunologia , Adulto , Alelos , Feminino , Genótipo , Antígenos HLA/imunologia , Antígenos HLA/metabolismo , Antígenos HLA-G , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Masculino , Resultado da Gravidez , Fatores de Risco , Resultado do Tratamento
15.
Phys Rev E Stat Nonlin Soft Matter Phys ; 64(4 Pt 2): 046201, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11690119

RESUMO

A method is proposed to reconstruct dynamic attractors by embedding of multivariate observations of dynamic nonlinear processes. The Takens embedding theory is combined with independent component analysis to transform the embedding into a vector space of linearly independent vectors (phase variables). The method is successfully tested against prediction of the unembedded state vector in two case studies of simulated chaotic processes.

17.
J Org Chem ; 66(4): 1297-309, 2001 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-11312960

RESUMO

The total syntheses of the potent protein kinase C inhibitors calphostins A, B, C, and D as well as a variety of structural analogues are reported. An aminobenzannulation reaction of an enantiopure chromium Fischer carbene complex is utilized to prepare a pentasubstituted naphthylamine. After optimization of side-chain substituents, conversion of the naphthylamine to an o-naphthoquinone was followed by biomimetic oxidative dimerization using trifluoroacetic acid and air yielding a 1:2 P/M mixture of atropisomeric perylenequinones. Thermal equilibration to a 3:1 P:M atropisomeric ratio and separation of the perylenequinones followed by side chain desymmetrization and functionalization led to the total synthesis of enantio- and diastereomerically pure calphostin C in only twelve steps from commercially available starting materials. In addition, calphostins A, B, D, and several structural analogues were prepared to evaluate biological activities.


Assuntos
Metano/análogos & derivados , Metano/química , Naftalenos/síntese química , Hidrocarbonetos , Isomerismo , Estrutura Molecular , Análise Espectral , Termodinâmica
18.
J Virol ; 75(1): 311-22, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11119601

RESUMO

Hepadnaviruses replicate by reverse transcription, which takes place in the cytoplasm of the infected hepatocyte. Viral RNAs, including the pregenome, are transcribed from a covalently closed circular (ccc) viral DNA that is found in the nucleus. Inhibitors of the viral reverse transcriptase can block new DNA synthesis but have no direct effect on the up to 50 or more copies of cccDNA that maintain the infected state. Thus, during antiviral therapy, the rates of loss of cccDNA, infected hepatocytes (1 or more molecules of cccDNA), and replicating DNAs may be quite different. In the present study, we asked how these losses compared when woodchucks chronically infected with woodchuck hepatitis virus were treated with L-FMAU [1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl) uracil], an inhibitor of viral DNA synthesis. Viremia was suppressed for at least 8 months, after which drug-resistant virus began replicating to high titers. In addition, replicating viral DNAs were virtually absent from the liver after 6 weeks of treatment. In contrast, cccDNA declined more slowly, consistent with a half-life of approximately 33 to 50 days. The loss of cccDNA was comparable to that expected from the estimated death rate of hepatocytes in these woodchucks, suggesting that death of infected cells was one of the major routes for elimination of cccDNA. However, the decline in the actual number of infected hepatocytes lagged behind the decline in cccDNA, so that the average cccDNA copy number in infected cells dropped during the early phase of therapy. This observation was consistent with the possibility that some fraction of cccDNA was distributed to daughter cells in those infected hepatocytes that passed through mitosis.


Assuntos
Antivirais/farmacologia , Arabinofuranosiluracila/análogos & derivados , DNA Viral/análise , Vírus da Hepatite B da Marmota/efeitos dos fármacos , Hepatócitos/virologia , Sequência de Aminoácidos , Animais , Arabinofuranosiluracila/farmacologia , DNA Circular/análise , DNA Viral/biossíntese , Resistência a Medicamentos , Vírus da Hepatite B da Marmota/genética , Cinética , Lamivudina/farmacologia , Marmota , Dados de Sequência Molecular
19.
J Immunol ; 165(12): 7025-34, 2000 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-11120830

RESUMO

Many leader-derived peptides require TAP for presentation by class I molecules. This TAP dependence can either be ascribed to the inability of proteases resident in the endoplasmic reticulum (ER) to trim leader peptide precursors into the appropriate epitope or the failure of a portion of the leader segment to gain access to the lumen of the ER. Using the Qa-1 binding epitope, Qdm derived from a class Ia leader as a model, we show that many cell types lack ER protease activity to trim this peptide at its C terminus. However, both T1 and T2 cells contain appropriate protease activity to process the full length D(d) leader (DL) when introduced into the ER lumen. Nevertheless, both T1 cells treated with the TAP inhibitor ICP47 and TAP(-) T2 cells fail to present this epitope from either the intact D(d) molecule or a minigene encoding the DL. This indicates that the portion of the leader containing Qdm does not gain access to the ER. However, changing the Arg at P7 of the DL to a Cys can alter its trafficking and allows for TAP-independent presentation of the Qdm epitope.


Assuntos
Apresentação de Antígeno , Antígenos de Histocompatibilidade Classe I/metabolismo , Sinais Direcionadores de Proteínas , Sequência de Aminoácidos , Animais , Transporte Biológico/imunologia , Células Clonais , Testes Imunológicos de Citotoxicidade , Endopeptidases/metabolismo , Retículo Endoplasmático/enzimologia , Retículo Endoplasmático/imunologia , Retículo Endoplasmático/metabolismo , Epitopos de Linfócito T/metabolismo , Antígenos H-2/metabolismo , Células HeLa , Antígeno de Histocompatibilidade H-2D , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Linfócitos T Citotóxicos/metabolismo
20.
J Virol ; 74(24): 11754-63, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11090175

RESUMO

Treatment of hepatitis B virus carriers with the nucleoside analog lamivudine suppresses virus replication. However, rather than completely eliminating the virus, long-term treatment often ends in the outgrowth of drug-resistant variants. Using woodchucks chronically infected with woodchuck hepatitis virus (WHV), we investigated the consequences of combining lamivudine treatment with immunotherapy mediated by an adenovirus superinfection. Eight infected woodchucks were treated with lamivudine and four were infected with approximately 10(13) particles of an adenovirus type 5 vector expressing beta-galactosidase. Serum samples and liver biopsies collected following the combination therapy revealed a 10- to 20-fold reduction in DNA replication intermediates in three of four woodchucks at 2 weeks after adenovirus infection. At the same time, covalently closed circular DNA (cccDNA) and viral mRNA levels both declined about two- to threefold in those woodchucks, while mRNA levels for gamma interferon and tumor necrosis factor alpha as well as for the T-cell markers CD4 and CD8 were elevated about twofold. Recovery from adenovirus infection was marked by elevation of sorbitol dehydrogenase, a marker for hepatocyte necrosis, as well as an 8- to 10-fold increase in expression of proliferating cell nuclear antigen, a marker for DNA synthesis, indicating significant hepatocyte turnover. The fact that replicative DNA levels declined more than cccDNA and mRNA levels following adenovirus infection suggests that the former decline either was cytokine induced or reflects instability of replicative DNA in regenerating hepatocytes. Virus titers in all four woodchucks were only transiently suppressed, suggesting that the effect of combination therapy is transient and, at least under the conditions used, does not cure chronic WHV infections.


Assuntos
Adenoviridae/imunologia , Vírus da Hepatite B da Marmota/efeitos dos fármacos , Vírus da Hepatite B da Marmota/imunologia , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Imunoterapia , Lamivudina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Animais , Quimioterapia Combinada , Hepatite B Crônica/virologia , Marmota/virologia , Replicação Viral/efeitos dos fármacos
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