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1.
Prostate Cancer Prostatic Dis ; 24(3): 903-909, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33767355

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer is associated with adverse effects, such as obesity and metabolic syndrome, which increase cardiovascular risk, the most common cause of non-cancer mortality in men diagnosed with prostate cancer. The Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP) was created to determine the feasibility of conducing a comprehensive lifestyle modification intervention in men on ADT for prostate cancer and determine its early efficacy in reducing obesity and metabolic syndrome. METHODS: A single-arm, open-label clinical trial was conducted by recruiting 31 men diagnosed with prostate cancer and exposed to ADT within the last 5 years. A multicomponent lifestyle modification program was delivered weekly for 16 weeks by a trained health coach. This was followed by 8 weeks of passive follow-up resulting in a total trial duration of 24 weeks. Feasibility was determined by calculating study recruitment, retention, and adherence rates. Weight and components of metabolic syndrome (waist circumference, triglycerides (TG), high-density lipoprotein (HDL), serum glucose, and blood pressure (BP)) were measured at baseline, 12, and 24 weeks. RESULTS: Recruitment, retention, and adherence rates were 47.1%, 90.3%, and 100%, respectively. Statistically significant improvements were noted between baseline and end of study measurements for weight (206.3 vs. 191.3 lbs, p < 0.001), waist (41.3 vs. 38.8 inches, p < 0.001), systolic BP (144.1 vs. 133.4 mm of Hg, p = 0.014), diastolic BP (83.3 vs. 76.2 mm of Hg, p = 0.0056), TG (146.0 vs. 113.8 mg/dl, p = 0.022), HDL (51.1 vs. 55.0 mg/dl, p = 0.012), and serum glucose (114.0 vs. 103.2 mg/dl, p = 0.013). CONCLUSION: CLIPP demonstrates feasibility and early efficacy of a multicomponent lifestyle modification intervention toward addressing obesity as well as components of metabolic syndrome in men on ADT for prostate cancer. This study provides strong preliminary data to develop future clinical trials in this population.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Peso Corporal , Estilo de Vida , Síndrome Metabólica/prevenção & controle , Obesidade/prevenção & controle , Neoplasias da Próstata/tratamento farmacológico , Adulto , Idoso , Estudos de Viabilidade , Seguimentos , Humanos , Masculino , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Obesidade/induzido quimicamente , Obesidade/patologia , Prognóstico , Neoplasias da Próstata/patologia
2.
Contemp Clin Trials Commun ; 21: 100701, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33511299

RESUMO

BACKGROUND: Although androgen deprivation therapy (ADT) for prostate cancer demonstrates improved overall and disease-free survival, it is associated with adverse effects such as obesity and metabolic syndrome that increase risk of cardiometabolic disease and diabetes type 2. ADT also leads to fatigue, depression and erectile dysfunction, which reduce quality of life (QoL). Lifestyle modification has shown promise in reducing obesity, metabolic syndrome and diabetes type 2 in other disease types. However, there is a paucity of data regarding the utility of lifestyle modification in men receiving ADT for prostate cancer. METHODS: The primary aim of the Comprehensive Lifestyle Improvement Program for Prostate Cancer-2 (CLIPP2) is to test the feasibility of conducting a 24-week lifestyle modification intervention in men on ADT for prostate cancer. Additionally, it will also determine the effect of this intervention on weight loss, cardiometabolic markers (secondary aim and markers of interest: serum glucose, insulin resistance, hemoglobin A1C and lipid panel), and QoL (tertiary aim). The intervention will be delivered weekly via telephone for the first 10 weeks and bi-weekly for the remaining 14 weeks. Questionnaires and serum samples will be collected at baseline, week 12, and week 24. Anthropometric measurements will be collected at baseline, week 6, week 12, week 18 and week 24. RESULTS: We hypothesize that the CLIPP2 intervention will produce a 7% weight loss that will result in improved markers associated with cardiometabolic disease and type 2 diabetes in the study population. CONCLUSION: Results will provide insight into the role of lifestyle modification in addressing ADT adverse effects as well as provide preliminary data to inform the development of future lifestyle interventions in this area. TRIAL REGISTRATION: NCT04228055 Clinicaltrials. gov.

3.
Ann Oncol ; 30(3): 478-485, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30698666

RESUMO

BACKGROUND: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. MATERIALS AND METHODS: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. RESULTS: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). CONCLUSION: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.


Assuntos
Inflamação/sangue , Neoplasias Pulmonares/sangue , Metabolismo , Vitamina B 6/sangue , Adulto , Idoso , Feminino , Humanos , Inflamação/patologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Ácido Piridóxico/metabolismo , Fatores de Risco , Fumantes
4.
Ann Oncol ; 29(6): 1468-1475, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29617726

RESUMO

Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3). Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables. Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology. Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Deficiência de Vitamina D/fisiopatologia , Vitamina D/sangue , Adenocarcinoma/sangue , Adenocarcinoma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Saúde Global , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/sangue , Vitaminas/sangue , Adulto Jovem
5.
Nutr Cancer ; 69(2): 238-247, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28094571

RESUMO

No studies have evaluated the association between the dietary inflammatory index (DII) and colorectal adenoma recurrence. DII scores were calculated from a baseline food frequency questionnaire. Participants (n = 1727) were 40-80 years of age, enrolled in two Phase III clinical trials, who had ≥1 colorectal adenoma(s) removed within 6 months of study registration, and a follow-up colonoscopy during the trial. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). No statistically significant associations were found between DII and odds of colorectal adenoma recurrence [ORs (95% CIs) = 0.93 (0.73, 1.18) and 0.95 (0.73, 1.22)] for subjects in the second and third DII tertiles, respectively, compared to those in the lowest tertile (Ptrend = 0.72). No associations were found for recurrent colorectal adenoma characteristics, including advanced recurrent adenomas, large size, villous histology, or anatomic location. While our study did not support an association between a proinflammatory diet and colorectal adenoma recurrence, future studies are warranted to elucidate the role of a proinflammatory diet on the early stages of colorectal carcinogenesis.


Assuntos
Adenoma/etiologia , Neoplasias Colorretais/etiologia , Dieta/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
J Natl Cancer Inst ; 108(3)2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26668177

RESUMO

BACKGROUND: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. METHODS: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. RESULTS: After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). CONCLUSION: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence.


Assuntos
Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/epidemiologia , Terapia de Reposição de Estrogênios , Estrogênios Conjugados (USP)/administração & dosagem , Estrogênios Conjugados (USP)/efeitos adversos , Acetato de Medroxiprogesterona/administração & dosagem , Acetato de Medroxiprogesterona/efeitos adversos , Idoso , Método Duplo-Cego , Esquema de Medicação , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/cirurgia , Terapia de Reposição de Estrogênios/efeitos adversos , Terapia de Reposição de Estrogênios/métodos , Feminino , Humanos , Histerectomia , Incidência , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Razão de Chances , Pós-Menopausa , Estados Unidos/epidemiologia , Saúde da Mulher
7.
Int J Obes (Lond) ; 36(9): 1158-64, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22689071

RESUMO

OBJECTIVE: To determine whether alcohol consumption is associated with incident overweight or obesity in normal-weight, postmenopausal women. DESIGN: Prospective cohort study considering baseline alcohol consumption and subsequent weight change over 7 years. SUBJECTS: 15,920 normal-weight (body mass index (BMI): 18.5 to <25 kg m(-2)), postmenopausal women enrolled in the Women's Health Initiative Clinical Trial. MEASUREMENTS: Body weight change, and incident overweight and obesity (BMI, 25.0 to <30 and ≥ 30 kg m(-2)) over 7 years. RESULTS: One-third of the 13,822 women included in the analytical cohort reported no alcohol consumption. BMI differed little between abstainers (22.8±1.58 kg m(-2)) and alcohol consumers in the upper quintile (22.7±1.53 kg m(-2)). Among normal-weight women, the risk of becoming overweight or obese over a 7-year follow-up period was 35% or 88% lower, respectively, for women in the upper quintile of alcohol intake relative to abstainers (hazard ratio (HR), 0.65; 95% confidence interval (CI), 0.58-0.73; or HR, 0.12; 95% CI, 0.05-0.25, respectively). Risk for overweight and obesity was not significantly modified by age. Wine consumption showed the greatest protective association for risk of overweight (HR, 0.75; 95% CI, 0.68-0.84), followed by liquor (HR, 0.85; 95% CI, 0.78-0.93) and beer (HR, 0.90; 95% CI, 0.82-1.00). CONCLUSION: Postmenopausal women of normal weight who report moderate alcohol intake have a reduced risk of becoming overweight or obese over time. Perhaps, weight control measures in this population should target behaviors other than reduction in alcohol for those of normal BMI consuming moderate amounts.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Obesidade/epidemiologia , Pós-Menopausa , Comportamento de Redução do Risco , Saúde da Mulher , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/prevenção & controle , Índice de Massa Corporal , Estudos de Coortes , Feminino , Promoção da Saúde , Humanos , Incidência , Pessoa de Meia-Idade , Obesidade/prevenção & controle , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Estados Unidos/epidemiologia
8.
Front Immunol ; 3: 87, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22586427

RESUMO

Most monoclonal antibodies (mAbs) generated from humans infected or vaccinated with the 2009 pandemic H1N1 (pdmH1N1) influenza virus targeted the hemagglutinin (HA) stem. These anti-HA stem mAbs mostly used IGHV1-69 and bound readily to epitopes on the conventional seasonal influenza and pdmH1N1 vaccines. The anti-HA stem mAbs neutralized pdmH1N1, seasonal influenza H1N1 and avian H5N1 influenza viruses by inhibiting HA-mediated fusion of membranes and protected against and treated heterologous lethal infections in mice with H5N1 influenza virus. This demonstrated that therapeutic mAbs could be generated a few months after the new virus emerged. Human immunization with the pdmH1N1 vaccine induced circulating antibodies that when passively transferred, protected mice from lethal, heterologous H5N1 influenza infections. We observed that the dominant heterosubtypic antibody response against the HA stem correlated with the relative absence of memory B cells against the HA head of pdmH1N1, thus enabling the rare heterosubtypic memory B cells induced by seasonal influenza and specific for conserved sites on the HA stem to compete for T-cell help. These results support the notion that broadly protective antibodies against influenza would be induced by successive vaccination with conventional influenza vaccines based on subtypes of HA in viruses not circulating in humans.

10.
J Hum Nutr Diet ; 23(6): 590-600, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20807303

RESUMO

BACKGROUND: Overweight status after breast cancer treatment may increase a woman's risk for recurrent disease and/or early onset cardiovascular disease. Green tea has been proposed to promote weight loss and favourably modify glucose, insulin and blood lipids. This pilot study tested the effect of daily decaffeinated green tea consumption for 6 months on weight and body composition, select metabolic parameters and lipid profiles in overweight breast cancer survivors. METHODS: The effect of daily decaffeinated green tea intake on weight, body composition and changes in resting metabolic rate, energy intake, glucose, insulin, homeostasis model assessment--insulin resistance (HOMA-IR) and lipids was evaluated in overweight breast cancer survivors. Participants had a mean weight of 80.2 kg; body mass index (BMI) 30.1 kg m⁻²; and body fat 46.4%. Participants (n = 54) were randomised to 960 mL of decaffeinated green or placebo tea daily for 6 months. RESULTS: Mean (SD) tea intake among study completers (n = 39) was 5952 (1176) mL week⁻¹ and was associated with a significant reduction in energy intake (P = 0.02). Change in body weight of -1.2 kg (green tea) versus +0.2 kg (placebo) suggests a weight change effect, although this was not statistically significant. Decaffeinated green tea intake was associated with elevated high-density lipoprotein (HDL) levels (P = 0.003) and nonsignificant improvements in the HDL/LDL ratio and HOMA-IR (-1.1 ± 5.9: green tea; +3.2 ± 7.2: herbal). CONCLUSIONS: Intake of decaffeinated green tea for 6 months was associated with a slight reduction in body weight and improved HDL and glucose homeostasis in overweight breast cancer survivors.


Assuntos
Composição Corporal , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Metabolismo Energético , Sobrepeso/complicações , Chá , Idoso , Biomarcadores/sangue , Glicemia/análise , Neoplasias da Mama/fisiopatologia , Proteínas de Caenorhabditis elegans , Método Duplo-Cego , Ingestão de Energia , Exercício Físico , Feminino , Humanos , Insulina/sangue , Lipídeos/sangue , Pessoa de Meia-Idade , Sobrepeso/fisiopatologia , Fitoterapia , Projetos Piloto , Placebos , Fatores de Transcrição , Redução de Peso
11.
Protein Expr Purif ; 23(1): 8-13, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11570840

RESUMO

Hsp47 is regarded as a collagen-specific chaperone with several suggested roles in collagen biosynthesis under normal and disease conditions. We describe here a procedure for the expression and purification of Hsp47 in Escherichia coli using the IMPACT expression system (New England Biolabs) where the guest gene is fused to the adduct, intein, with a chitin-binding domain. Use of this system resulted in relatively high levels of soluble Hsp47 compared to other available protocols, especially when the bacterial cells were induced at 14 degrees C instead of 37 degrees C. The cell lysate was passed through a chitin-Sepharose affinity column and Hsp47 was cleaved from intein using beta-mercaptoethanol. Minor degradation products were subsequently removed using a hydroxylapatite column to yield milligram amounts of pure and active protein suitable for structural studies. Gel electrophoretic analysis of the purified protein indicated the presence of a small proportion of trimeric species when non-reducing conditions were used. The ability to form a trimer may be important for its role as a chaperone. The IMPACT system allows for radiolabelling of purified Hsp47 with (35)S for use in binding experiments. Illustrative data on collagen binding by (35)S-Hsp47 are shown.


Assuntos
Clonagem Molecular/métodos , Colágeno Tipo I/antagonistas & inibidores , Proteínas de Choque Térmico/biossíntese , Animais , Colágeno Tipo I/metabolismo , Escherichia coli/química , Escherichia coli/genética , Proteínas de Choque Térmico HSP47 , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/isolamento & purificação , Chaperonas Moleculares/biossíntese , Chaperonas Moleculares/genética , Chaperonas Moleculares/isolamento & purificação , Ligação Proteica , Ratos , Radioisótopos de Enxofre , Temperatura
12.
Am J Clin Nutr ; 73(6): 1107-12, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11382667

RESUMO

BACKGROUND: Ninety-eight percent of medical schools report nutrition as a component of medical education. However, most schools do not have an identifiable nutrition curriculum. Medical schools that do include nutrition have not evaluated its effect on clinical skills. OBJECTIVE: The objective was to determine the efficacy of an integrated undergraduate medical curriculum to increase the quantity of nutrition instruction and to advance nutrition clinical skills demonstrated by medical students. DESIGN: A quasiexperimental design was constructed to determine whether an integrated nutrition curriculum increased the performance on nutrition-oriented clinical examinations of medical school classes that received 1, 2, or 3 y of the curriculum. The evaluation of the curriculum focused on 3 areas: 1) hours of nutrition instruction, 2) the application of nutrition within a clinical setting, and 3) perceptions about the nutrition curriculum. The Objective Structured Clinical Examination (OSCE) nutrition score was compared between graduating classes by use of analysis of variance. Data from the American Association of Medical Colleges were analyzed to determine the change in the proportion of students who reported that the amount of time devoted to nutrition was adequate. RESULTS: The implementation of the integrated nutrition curriculum resulted in a doubling of the total hours of required instruction in the medical curriculum (35 compared with 75 h). The mean (+/-1 SEM) OSCE nutrition score significantly improved after the implementation of the curriculum (41.7 +/- 0.9% compared with 50.6 +/- 1.1%) and the percentage of students who reported that the amount of nutrition taught during medical school was inadequate decreased (68.4% compared with 11.5%). CONCLUSION: Medical students improved their clinical nutrition practice skills through participation in an integrated nutrition curriculum.


Assuntos
Atitude do Pessoal de Saúde , Educação de Graduação em Medicina , Ciências da Nutrição/educação , Adulto , Arizona , Estágio Clínico , Currículo , Feminino , Humanos , Masculino
13.
J Cancer Educ ; 15(3): 127-9, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11019756

RESUMO

R25 grant support from the NIH/NCI enabled the University of Arizona to assess nutrition education, develop and evaluate specific course content, and move toward comprehensive prevention-based nutrition education in 1991-1997. Hours of nutrition education increased to 115% over baseline, and students indicated greater satisfaction with the amount of nutrition instruction they received. Especially valuable was a course in prenatal and infant nutrition that paired each student with a pregnant patient. After the grant support ended, nutrition began to be crowded out of the curriculum by other, more traditional, topics, but a 57% gain over baseline was sustained. External support for nutrition education is urgently needed.


Assuntos
Currículo , Educação Médica/normas , Ciências da Nutrição/educação , Faculdades de Medicina , National Institutes of Health (U.S.) , Apoio à Pesquisa como Assunto , Estados Unidos
14.
J Pediatr Gastroenterol Nutr ; 31(3): 291-9, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10997375

RESUMO

BACKGROUND: The immune consequences of adding 20:4n-6 and 22:6n-3 fatty acids to preterm infant formula are not known. METHODS: The effect of feeding preterm infants (14-42 days of age) human milk (Human Milk group), infant formula (Formula group), or formula with added long-chain polyunsaturated fatty acids 20:4n-6 and 22:6n-3 (Formula + LCP group) on isolated peripheral blood lymphocytes (by flow cytometry) and lipid composition (by gas-liquid chromatography) was determined. Lymphocytes were stimulated in vitro with phytohemagglutinin to measure soluble interleukin (sIL)-2R and IL-10 production (by enzyme-linked immunosorbent assay). RESULTS: With age, the percentage of CD3+ CD4+ T cells and the percentage of CD20+ cells increased in the Human Milk and Formula + LCP groups (P < 0.05), but not in the unsupplemented Formula group. Compared with the Formula group, CD4+ cells from the Formula + LCP and Human Milk groups expressed more CD45R0 (antigen mature) and less CD45RA (antigen naive) at 42 days of age (P < 0.05). At 42 days, IL-10 production was lower (P < 0.05) in cells of the Formula group than in cells of the Human Milk group. Production of IL-10 by the cells of the Formula + LCP group was not different from that produced by the Human Milk group cells. An age-related decrease (P < 0.05) in sIL-2R production by Formula + LCP lymphocytes was observed, but sIL-2R production at 42 days in the Formula + LCP group did not differ significantly from that in the Human Milk group. Compared with Formula alone, adding LCP to formula resulted in a lower C18:2n-6 and higher C20:4n-6 content in lymphocyte phospholipids (P < 0.05). CONCLUSIONS: Adding LCP to a preterm infant formula resulted in lymphocyte populations, phospholipid composition, cytokine production, and antigen maturity that are more consistent with that in human milk-fed infants. This may affect the ability of the infant to respond to immune challenges.


Assuntos
Ácidos Graxos Insaturados/administração & dosagem , Alimentos Infantis , Recém-Nascido Prematuro/imunologia , Interleucina-10/biossíntese , Antígenos Comuns de Leucócito/sangue , Linfócitos/imunologia , Leite Humano/imunologia , Fatores Etários , Cromatografia Gasosa , Suplementos Nutricionais , Ensaio de Imunoadsorção Enzimática , Ácidos Graxos Insaturados/sangue , Feminino , Citometria de Fluxo , Idade Gestacional , Humanos , Imunofenotipagem , Lactente , Recém-Nascido , Contagem de Leucócitos , Lipídeos/sangue , Ativação Linfocitária , Linfócitos/química , Masculino
15.
Biochem J ; 349 Pt 3: 877-83, 2000 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-10903151

RESUMO

Hsp47, a 47 kDa heat shock protein whose expression level parallels that of collagen, has been regarded as a collagen-specific molecular chaperone. Studies from other laboratories have established the association of Hsp47 with the nascent as well as the triple-helical procollagen molecule in the endoplasmic reticulum and its dissociation from procollagen in the Golgi. One of several roles suggested for Hsp47 in collagen biosynthesis is the prevention of aggregation of procollagen in the endoplasmic reticulum. However, no experimental evidence has been available to verify this suggestion. In the present study we have followed the aggregation of mature triple-helical collagen molecules into fibrils by using turbidimetric measurements in the absence and presence of Hsp47. In the pH range 6-7, fibril formation of type I collagen, as monitored by turbidimetry, proceeds with a lag of approx. 10 min and levels off by approx. 60 min. The addition of Hsp47 at pH 7 effectively inhibits fibril formation at and above a 1:1 molar ratio of Hsp47 to triple-helical collagen. This inhibition is markedly pH-dependent, being significantly diminished at pH 6. CD and fluorescence spectral data of Hsp47 in the pH range 4.2-7.4 reveal a significant alteration in its structure at pH values below 6.2, with a decrease in alpha-helix and an increase in beta-structure. This conformational change is likely to be the basis of the decreased binding of Hsp47 to collagen in vitro at pH 6.3 as well as its inability to inhibit collagen fibril formation at this pH. Our results also provide a functional assay for Hsp47 that can be used in studies on collagen and Hsp47 interactions.


Assuntos
Colágeno/antagonistas & inibidores , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/metabolismo , Animais , Dicroísmo Circular , Colágeno/biossíntese , Proteínas de Choque Térmico HSP47 , Concentração de Íons de Hidrogênio , Conformação Proteica , Ratos , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Espectrometria de Fluorescência , Relação Estrutura-Atividade
18.
Anesth Analg ; 81(5): 973-81, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7486087

RESUMO

After thoracotomy some patients have discomfort, primarily in the rostral portion of their incisions. In this prospective, randomized study in 66 patients after lateral thoracotomy we evaluated whether, for equal fentanyl dosage in micrograms per kilogram, epidural infusion (lumbar catheter) of fentanyl 5 micrograms/mL provided better segmental analgesia (including the rostral portion of the incision) than a 10-micrograms/mL concentration infused at a rate half that used in the 5-micrograms/mL group. Ketorolac was used as an analgesic adjunct for nonincisional pain. Postoperative epidural fentanyl infusion included a 1-microgram/kg initial dose and an initial infusion rate of 1 microgram.kg-1.h-1 in both the 5-micrograms/mL and 10-micrograms/mL groups. Patients were evaluated for comfort level and pain relief while resting, taking a deep breath, coughing, and ambulating at eight times over 3 days using two visual analog scales for overall comfort and a verbal rating score (VRS) for segmental analgesia. There were no significant differences in demographics, surgical procedure, intraoperative fentanyl dose, side effects, rates of epidural fentanyl infusion, or total epidural fentanyl doses at 12, 24, 36, 48, and 60 h postbolus. Analgesia was effective in both groups. Although overall comfort levels were lower (i.e., indicated greater comfort) in the 5-micrograms/mL group in 6 of 8 visual analog scores (VASs) for comfort level and 20 of 24 VRSs for comfort level scores, and mean VRSs for the rostral portion of the incision were lower (i.e., indicated greater comfort) in the 5-micrograms/mL group at 21 of 24 evaluation subsets (one statistically significant), statistical significance was achieved in only six evaluation subsets.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Analgesia Epidural/métodos , Analgésicos Opioides/administração & dosagem , Fentanila/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Toracotomia/métodos , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Estudos Prospectivos
19.
Anal Chem ; 64(8): 848-53, 1992 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-1621998

RESUMO

Supercritical fluid extraction with carbon dioxide has been found to be effective for the isolation of residue levels (0.1-1 ppm) of 2,4-dichlorophenol from selected plant tissues. The 2,4-dichlorophenol residues were incompletely extracted with supercritical CO2 alone, since a substantial fraction of the 2,4-dichlorophenol was covalently attached to the plant matrix. An acid pretreatment procedure was developed to partially hydrolyze the plant tissue prior to extraction, releasing the bound 2,4-dichlorophenol residues. Steam distillation showed higher residue levels for field-treated straw samples. This is attributed to the greater degree of hydrolysis inherent in the steam distillation procedure. Supercritical CO2 extraction of field-treated seed samples showed higher levels of 2,4-dichlorophenol residues than did steam distillation. The supercritical fluid extractant was able to solvate 2,4-dichlorophenol residues in the interior of the seed and transport them to the surface for collection. The aqueous medium used in steam distillation was unable to penetrate the hydrophobic seed matrix to the same degree. While the actual extraction time experienced in supercritical fluid extraction was far less than that of steam distillation (45 min vs 6 h, respectively), the total sample preparation time was similar in both methods.


Assuntos
Dióxido de Carbono/química , Clorofenóis/isolamento & purificação , Resíduos de Praguicidas/isolamento & purificação , Plantas Comestíveis/química , Clorofenóis/química , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida
20.
J Am Diet Assoc ; 90(9): 1242-6, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2398215

RESUMO

A national survey was conducted to identify and differentiate influence techniques clinical dietitians use when interacting with physicians, to ascertain which of selected demographic variables explain variations in influence techniques used, and to identify and differentiate activities clinical dietitians perform. A three-part (influence, demographic, activity) questionnaire was developed and mailed to 600 randomly selected members of the Nutrition Support dietetic practice group. Usable responses were received from 458 dietitians, yielding a response rate of 77%. Factor analysis revealed that respondents assumed five of six possible postures of influence techniques (block/threaten, ingratiation, coalition, assertiveness, and transitional rationality) and three of four possible postures of activity (diet oriented, physician oriented, and case oriented). Multivariate analysis showed use of ingratiation techniques related inversely to age and education of practitioners, use of assertiveness techniques related inversely to age, and use of transitional rationality techniques related positively to age and education combined. The survey indicates that somewhat of a paradox exists among clinical dietitians; i.e., even though the percentage of selected practitioners performing high-level case-oriented activities has apparently declined since 1982, a critical number perceive themselves to be acculturating toward the sixth and highest influence (convincing rationality) and the highest activity (diagnosis and research orientation unique to dietetics) postures to be attained.


Assuntos
Dietética , Relações Interprofissionais , Médicos , Adulto , Feminino , Humanos , Inquéritos e Questionários
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