RESUMO
The periparturient period is a metabolically demanding time for dairy animals because of increased nutrient requirements for milk yield. The objective of this study was to investigate the effect of feeding Saccharomyces cerevisiae boulardii (CNCM I-1079), a commercial active dry yeast (ADY), in dairy cows on productive and metabolic measures during the periparturient period. Primiparous (n = 33) and multiparous (n = 35) cows were fed a close-up total mixed ration (TMR) before calving and a lactation TMR postpartum. Three weeks before expected calving time, animals were blocked by parity and body weight and then randomly assigned to either control group (control; n = 34) or treatment (ADY; n = 34). All animals were housed in a tie-stall barn with individual feed bunks; the ADY animals received supplementary Saccharomyces cerevisiae boulardii (CNCM I-1079), top dressed daily at a predicted dosage of 1.0 × 1010 cfu (12.5 g) per head. Blood samples were collected weekly along with milk yield and milk composition data; feed intake data were collected daily. Serum samples were analyzed for glucose, nonesterified fatty acid, ß-hydroxybutyrate, haptoglobin (Hp), and the cytokines tumor necrosis factor-α, IL-6, and IL-18. Colostrum samples collected within the first 6 to 10 h were analyzed for somatic cell score and IgG, IgA, and IgM concentrations. Data were analyzed using PROC GLIMMIX in SAS with time as a repeated measure; model included time, parity, treatment, and their interactions. The ADY groups had greater milk yield (39.0 ± 2.4 vs. 36.7 ± 2.3 kg/d) and tended to produce more energy-corrected milk with better feed efficiency. There was no difference in plasma glucose, serum nonesterified fatty acid, serum ß-hydroxybutyrate, Hp, IL-6, or IL-18 due to ADY treatment. The tumor necrosis factor-α increased in ADY-supplemented animals (1.17 ± 0.69 vs. 4.96 ± 7.7 ng/mL), though week, parity, and their interactions had no effect. Serum amyloid A tended to increase in ADY-supplemented animals when compared to control animals and was additionally affected by week and parity; there were no significant interactions. No difference in colostrum IgG, IgA, and IgM was observed between treatments. Supplementing transition cow TMR with ADY (CNCM I-1079) improved milk production and tended to improve efficiency in early lactation; markers of inflammation were also influenced by ADY treatment, though the immunological effect was inconsistent.
Assuntos
Saccharomyces boulardii , Saccharomyces cerevisiae , Gravidez , Feminino , Bovinos , Animais , Saccharomyces cerevisiae/metabolismo , Interleucina-18/metabolismo , Ácido 3-Hidroxibutírico , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Dieta/veterinária , Metabolismo Energético , Lactação , Leite/metabolismo , Ingestão de Alimentos , Período Pós-Parto/metabolismo , Ácidos Graxos não Esterificados , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina M , Ração Animal/análiseRESUMO
PURPOSE: To review the management of metastatic upper tract urothelial carcinoma (UTUC) including recent advances in targeted and immune therapies as an update to the 2014 joint international consultation on UTUC, co-sponsored by the Société Internationale d'Urologie and International Consultation on Urological Diseases. METHODS: A PubMed database search was performed between January 2013 and May 2016 related to the treatment of metastatic UTUC, and 54 studies were selected for inclusion. RESULTS: The management of patients with metastatic UTUC is primarily an extrapolation from evidence guiding the management of metastatic urothelial carcinoma of the bladder. The first-line therapy for metastatic UTUC is platinum-based combination chemotherapy. Standard second-line therapies are limited and ineffective. Patients with UTUC who progress following platinum-based chemotherapy are encouraged to participate in clinical trials. Recent advances in genomic profiling present exciting opportunities to guide the use of targeted therapy. Immunotherapy with checkpoint inhibitors has demonstrated extremely promising results. Retrospective studies provide support for post-chemotherapy surgery in appropriately selected patients. CONCLUSIONS: The management of metastatic UTUC requires a multi-disciplinary approach. New insights from genomic profiling using targeted therapies, novel immunotherapies, and surgery represent promising avenues for further therapeutic exploration.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/terapia , Neoplasias Renais/patologia , Neoplasias Ureterais/patologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma de Células de Transição/secundário , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Humanos , Imunoterapia , Indóis/administração & dosagem , Pelve Renal , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Paclitaxel/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Pirróis/administração & dosagem , Sorafenibe , Sunitinibe , Taxoides/administração & dosagem , GencitabinaRESUMO
A systematic study of photon and neutron radiation doses generated in high-intensity laser-solid interactions is underway at SLAC National Accelerator Laboratory. These laser-solid experiments are being performed using a 25 TW (up to 1 J in 40 fs) femtosecond pulsed Ti:sapphire laser at the Linac Coherent Light Source's (LCLS) Matter in Extreme Conditions (MEC) facility. Radiation measurements were performed with passive and active detectors deployed at various locations inside and outside the target chamber. Results from radiation dose measurements for laser-solid experiments at SLAC MEC in 2014 with peak intensity between 1018 and 7.1 × 1019 W cm-2 are presented.
Assuntos
Lasers , Nêutrons , Aceleradores de Partículas/instrumentação , Fótons , Monitoramento de Radiação/instrumentação , Monitoramento de Radiação/métodos , Óxido de Alumínio/química , Humanos , Monitoramento de Radiação/normas , Titânio/químicaRESUMO
OBJECTIVE: To assess and explain deviations from recommended practice in National Institute for Clinical Excellence (NICE) guidelines in relation to fetal heart monitoring. DESIGN: Qualitative study. SETTING: Large teaching hospital in the UK. SAMPLE: Sixty-six hours of observation of 25 labours and interviews with 20 midwives of varying grades. METHODS: Structured observations of labour and semistructured interviews with midwives. Interviews were undertaken using a prompt guide, audiotaped, and transcribed verbatim. Analysis was based on the constant comparative method, assisted by QSR N5 software. MAIN OUTCOME MEASURES: Deviations from recommended practice in relation to fetal monitoring and insights into why these occur. RESULTS: All babies involved in the study were safely delivered, but 243 deviations from recommended practice in relation to NICE guidelines on fetal monitoring were identified, with the majority (80%) of these occurring in relation to documentation. Other deviations from recommended practice included indications for use of electronic fetal heart monitoring and conduct of fetal heart monitoring. There is evidence of difficulties with availability and maintenance of equipment, and some deficits in staff knowledge and skill. Differing orientations towards fetal monitoring were reported by midwives, which were likely to have impacts on practice. The initiation, management, and interpretation of fetal heart monitoring is complex and distributed across time, space, and professional boundaries, and practices in relation to fetal heart monitoring need to be understood within an organisational and social context. CONCLUSION: Some deviations from best practice guidelines may be rectified through straightforward interventions including improved systems for managing equipment and training. Other deviations from recommended practice need to be understood as the outcomes of complex processes that are likely to defy easy resolution.
Assuntos
Atitude do Pessoal de Saúde , Cardiotocografia , Enfermeiros Obstétricos/psicologia , Prática Profissional/normas , Feminino , Humanos , Satisfação no Emprego , Tocologia/educação , Enfermeiros Obstétricos/educação , Papel do Profissional de Enfermagem , Complicações do Trabalho de Parto/enfermagem , Guias de Prática Clínica como Assunto , GravidezRESUMO
A novel series of benzylamine, potassium channel openers (KCOs) is presented as part of our program toward designing new, bladder-selective compounds for the treatment of urge urinary incontinence (UUI). We have found that the in vitro potency of (R)-4-[3,4-dioxo-2-(1,2, 2-trimethyl-propylamino)-cyclobut-1-enylamino]-3-ethyl-benzo nitrile 1 in the relaxation of precontracted rat detrusor strips can also be obtained with cyanobenzylamine derivative 4 (IC(50) = 0.29 microM) (Figure 3). Addition of a 2-Cl substituted benzylamine moiety and changing the alkylamino substituent of 4 to a t-Bu amine gives 31 (IC(50) = 0.14 microM)-a compound with similar in vitro potency as 4 as well as relaxant activity on bladder smooth muscle in vivo when administered orally (31, ED(50) = 3 mg/kg) in a rodent model of bladder instability. Further modifications, particularly the replacement of the t-Bu amino substituent with a tert-amylamine, gave a similarly active compound 60 (IC(50) = 0.10 microM) which shows excellent in vivo efficacy (ED(50) = 0.6 mg/kg). Moreover, 60, 3-(2,4-dichloro-6-methyl-benzylamino)-4-(1, 1-dimethyl-propylamino)-cyclobut-3-ene-1,2-dione (WAY-151616), shows excellent tissue selectivity for bladder K channels over arterial tissue (60, MAP ED(20) = 100 mg/kg; selectivity: MAP ED(20)/bladder ED(50) = 166). Other manipulations of the benzylamino cyclobutenediones, acylation of the benzylamine, conversion of the benzylamine substituent to a benzamide, homologation of the benzylamine to a phenethylamine, and incorporation of a methyl group at the benzyl carbon, all led to substantial loss of in vitro activity, although some in vivo activity was maintained in the acylated analogues. Compound 60 represents an attractive candidate for development in the treatment of UUI.
Assuntos
Benzilaminas/síntese química , Ciclobutanos/síntese química , Canais de Potássio/agonistas , Bexiga Urinária/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Benzilaminas/química , Benzilaminas/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Ciclobutanos/química , Ciclobutanos/farmacologia , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Cloreto de Potássio/farmacologia , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Bexiga Urinária/fisiologia , Incontinência Urinária/tratamento farmacológicoRESUMO
A structurally novel series of adenosine 5'-triphosphate-sensitive potassium (K(ATP)) channel openers is described. As part of our efforts directed toward identifying novel, bladder-selective potassium channel openers (KCOs) targeted for urge urinary incontinence (UUI), we found that bioisosteric replacement of the N-cyanoguanidine moiety of pinacidil (1, Figure 1) with a diaminocyclobutenedione template afforded squaric acid analogue 2, the prototype of a novel series of K(ATP) channel openers with unique selectivity for bladder smooth muscle in vivo. Further modification of the heterocyclic ring to give substituted aryl derivatives (3) afforded potent KCOs that possessed the desired detrusor selectivity when administered orally. The effects of these potassium channel agonists on bladder contractile function was studied in vitro using isolated rat detrusor strips. Potent relaxants were evaluated in vivo in a rat model of bladder instability. Lead compounds were evaluated concomitantly in normotensive rats for their effects on mean arterial blood pressure (MAP) and heart rate as a measure of in vivo bladder selectivity. (R)-4-[3,4-Dioxo-2-(1,2, 2-trimethyl-propylamino)-cyclobut-1-enylamino]-3-ethyl-benzo nitrile (79) met our potency and selectivity criteria and represents an attractive development candidate for the treatment of UUI. Electrophysiological studies using isolated rat bladder detrusor myocytes have demonstrated that compound 79 produces significant hyperpolarization which is glyburide-reversed, thus consistent with the activation of K(ATP). The design, synthesis, structure-activity relationships (SAR), and pharmacological activity associated with this series of novel KCOs will be discussed.
Assuntos
Ciclobutanos/síntese química , Nitrilas/síntese química , Canais de Potássio/agonistas , Bexiga Urinária/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Ciclobutanos/química , Ciclobutanos/farmacologia , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/citologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Nitrilas/química , Nitrilas/farmacologia , Técnicas de Patch-Clamp , Cloreto de Potássio/farmacologia , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Bexiga Urinária/citologia , Bexiga Urinária/fisiologia , Incontinência Urinária/tratamento farmacológicoRESUMO
Excessive nitric oxide (NO) production in septic shock is thought to contribute to the associated profound hypotension. Here we show that despite induction of NO synthase (NOS) in the hearts of endotoxin-treated rats, coronary vascular responses to the contractile peptide endothelin-1, were not modified. This was not due to any change in the expression of endothelin receptors. However, when the substrate for NOS, L-arginine, was added to the perfusate, increases in coronary perfusion pressure stimulated by endothelin were reduced in hearts from endotoxin-treated animals compared to those from controls. In addition, L-glutamine, which blocks the generation of L-arginine from intracellular stores, enhanced the increase in perfusion pressure stimulated by endothelin-1. These data suggest that L-arginine becomes rate limiting for the production of NO in the coronary vessels during septic shock. Moreover, it suggests that vascular reactivity may be modulated positively or negatively by supplementation with the relevant amino acids.
Assuntos
Arginina/farmacologia , Vasos Coronários/metabolismo , Glutamina/farmacologia , Óxido Nítrico/biossíntese , Choque Séptico/metabolismo , Animais , Endotelina-1/farmacologia , Endotoxinas/toxicidade , Indução Enzimática , Masculino , Miocárdio/enzimologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , RNA Mensageiro/análise , Ratos , Ratos WistarRESUMO
First trimester nausea is associated with gastric slow wave dysrhythmias (tachygastria, bradygastria). We tested the roles of meal composition and caloric content on nausea and slow wave rhythm in 14 nauseated pregnant women. Electrogastrography quantified dysrhythmic activity and signal power responses to meals. Symptomatic women reported mild to moderate nausea and exhibited increased dysrhythmias during fasting (P < 0.05). Protein-predominant meals reduced nausea and dysrhythmic activity to greater degrees than equicaloric carbohydrate and fat meals and noncaloric meals (P < 0.05). Meal consistency did not affect symptom responses, although liquid meals decreased dysrhythmias more than solids (P < 0.05). Carbohydrates and fats increased electrogastrographic power to similar degrees as proteins, whereas responses to noncaloric meals were less. In conclusion, protein meals selectively reduce nausea and gastric slow wave dysrhythmias in first trimester pregnancy. Meal consistency is a limited factor in the favorable effects of protein. Electrogastrographic power changes do not explain the symptom response to protein. Thus dietary modulation of gastric myoelectric rhythm with protein supplementation may provide symptomatic benefit in nausea of pregnancy.
Assuntos
Proteínas Alimentares/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Náusea/prevenção & controle , Complicações na Gravidez/prevenção & controle , Gastropatias/prevenção & controle , Gastropatias/fisiopatologia , Adulto , Ingestão de Alimentos/fisiologia , Eletrofisiologia , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Estômago/fisiologiaRESUMO
The management of a ten-year-old female with an Angle Class II division 1 malocclusion is followed for nearly ten years, through active treatment, until follow-up some years later. Note is made of: the duration of the overall active treatment period; the need for considerable patient cooperation; the fact that the lower incisors did not move forward on their underlying bone while still moving forward in relation to the APo line; and the fact that, in this instance, the third molars were chosen as appropriate teeth for extraction.
Assuntos
Dentição Mista , Má Oclusão Classe II de Angle/terapia , Criança , Assistência Odontológica Integral , Feminino , Seguimentos , Humanos , Incisivo/patologia , Dente Serotino/cirurgia , Ortodontia Interceptora , Planejamento de Assistência ao Paciente , Cooperação do Paciente , Extração Seriada , Técnicas de Movimentação Dentária , Resultado do TratamentoRESUMO
Novel antiherpetic 3-quinolinecarboxamides were discovered as part of a drug discovery program at Sterling Winthrop Inc. A major goal of this research was to identify novel non-nucleoside agents possessing activity against acyclovir resistant herpes simplex virus. From screening compound libraries in an HSV-2 plaque reduction assay, 1-ethyl-1,4-dihydro-4-oxo-7-(4-pyridinyl)-3-quinolinecarboxamide (1) emerged as an attractive lead structure. By modifying the quinoline ring at the 1-, 2-, 3-, 4-, and 7-positions, analogues were identified that have up to 5-fold increased in vitro potency relative to acyclovir. In a single dose mouse model of infection the 1-(4-FC6H4) analogue 17, one of the most potent derivatives in vitro, displayed comparable oral antiherpetic efficacy to acyclovir at 1/16 the dose; in a multiple dose regimen, however, it was 2-fold less potent. Mechanism of action studies indicate that these new compounds interact with a different, as yet undefined, molecular target than acyclovir.
Assuntos
Antivirais/química , Antivirais/farmacologia , Quinolinas/química , Quinolinas/farmacologia , Aciclovir/farmacologia , Animais , Antivirais/síntese química , Chlorocebus aethiops , Modelos Animais de Doenças , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Herpesvirus Humano 2/efeitos dos fármacos , Humanos , Camundongos , Quinolinas/síntese química , Simplexvirus/efeitos dos fármacos , Relação Estrutura-Atividade , Células Vero , Ensaio de Placa ViralRESUMO
OBJECTIVES: To determine the effect of lansoprazole and high dose ranitidine on the accuracy of the 14C-urea breath test (UBT). Using intragastric pH recordings, we correlated the effect of these agents on the UBT with their potency of gastric acid suppression. METHODS: Patients with active Helicobacter pylori infection underwent a baseline UBT before receiving 14 days of lansoprazole (30 mg/day) or ranitidine (300 mg b.i.d.). During therapy, patients were asked to undergo 24-h intragastric pH monitoring. Repeat breath testing was performed 1 day after completion of the study drugs. If the UBT was equivocal or negative (14CO2 excretion was < 200 dpm), further UBTs were completed until the 14CO2 excretion was > 200 dpm. RESULTS: Thirteen patients received lansoprazole. Eight of thirteen patients developed a negative or equivocal UBT. All patients had 14CO2 excretion > 200 dpm 5 days after the cessation of lansoprazole. Eleven patients received ranitidine. Ranitidine led to equivocal or false negative UBTs in 2 of 11 cases. This effect resolved within 5 days of stopping ranitidine. Intragastric pH recordings revealed that the patients who experienced the most profound gastric acid suppression were those that developed equivocal or false negative UBTs. CONCLUSIONS: Lansoprazole significantly affected the accuracy of the UBT, causing equivocal or false negative results in 61%. High dose ranitidine affected the breath test in only 18%. The ability of these drugs to suppress gastric acid secretion predicted those patients who developed equivocal or false-negative UBTs. The effect on the accuracy of the UBT resolved within 5 days of drug cessation.
Assuntos
Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Testes Respiratórios , Radioisótopos de Carbono , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Omeprazol/análogos & derivados , Ranitidina/uso terapêutico , Ureia , 2-Piridinilmetilsulfinilbenzimidazóis , Dióxido de Carbono/análise , Reações Falso-Negativas , Feminino , Previsões , Ácido Gástrico/metabolismo , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Humanos , Concentração de Íons de Hidrogênio , Lansoprazol , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial , Omeprazol/uso terapêutico , Estômago/efeitos dos fármacos , Estômago/fisiologia , Ureia/análiseRESUMO
We have demonstrated that in aged mice, the titer of serum antibody induced against tetanus toxoid correlates with resistance to local paralysis caused by injection of tetanus toxin. Only mice immunized shortly after oral dosing with DHEAS demonstrated high serum antibody titers and complete protection from paralysis. These results became the basis for initiating proof-of-principle studies in human volunteers above age 65 using a licensed influenza vaccine and tetanus toxoid in two independent studies. The use of an oral delivery form of DHEAS before influenza vaccination was associated with a demonstrable increase in the number of individuals with a fourfold increase in HAI titers following vaccination. The overall mean increase in HAI titers was highest in the DHEAS-treated group. The use of DHEAS in the immunization of elderly subjects against tetanus toxoid, while unable to enhance the responses, was not a detriment to antibody response. We conclude that further studies will justify the use of DHEAS as an adjuvant for antigens that represent primary responses in the elderly.
Assuntos
Adjuvantes Imunológicos , Envelhecimento , Desidroepiandrosterona/análogos & derivados , Vacinas contra Influenza/imunologia , Idoso , Animais , Anticorpos Antivirais/biossíntese , Desidroepiandrosterona/administração & dosagem , Sulfato de Desidroepiandrosterona , Feminino , Humanos , Masculino , Camundongos , Toxoide Tetânico/imunologia , VacinaçãoRESUMO
Oxford House is a self-help, self-governed, democratic communal-living environment for recovering alcoholics and polysubstance abusers. In this study, 134 male residents (M age = 34 years old) were personally interviewed on their recovery process and, in particular, on their experience with 12-step programs such as Alcoholics Anonymous (AA). Most residents (76%) reported they attended weekly AA meetings to assist in their recovery, mainly to acquire effective techniques to maintain sobriety (72%). Many AA attendees (43%) claimed no sense of spirituality prior to joining AA, and for most of these men (71%), attendance at weekly meetings was not motivated by "spirituality" aspects of the program. In contrast, the majority of residents (53%) attending weekly AA meetings claimed that a sense of fellowship with similar recovering others was their reason for program involvement. It appears that among men living in a communal setting with other recovering addicts, the need for social support for sobriety from similar others continues beyond the confines of their residence.
Assuntos
Alcoolismo/reabilitação , Casas para Recuperação , Religião e Psicologia , Apoio Social , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Adulto , Alcoolismo/psicologia , Humanos , Controle Interno-Externo , Masculino , Pessoa de Meia-Idade , Motivação , Determinação da Personalidade , Meio Social , Transtornos Relacionados ao Uso de Substâncias/psicologia , Temperança/psicologiaRESUMO
This study sought to establish whether administration of dehydroepiandrosterone (DHEA) or its sulfate derivative to aged mice could effectively correct the immunosenescent phenotype. Supplemental DHEA sulfate and topical DHEA fully corrected the age-associated dysregulated production of T cell lymphokines by cells from all of the different lymphoid organs tested. Either DHEA or DHEA sulfate supplementation promoted enhanced antibody responses against recombinant hepatitis B surface antigen (rHBsAg) by the aged recipients when incorporated directly into the vaccine. When DHEA was provided either topically or was incorporated directly into vaccine, vigorous primary and secondary antibody responses were detected in the aged mice given a single administration of DHEA, regardless of the mode of administration. It was also established that DHEA treatment could enhance specific antibody responses to rHBsAg in aged animals that had previously not been effectively immunized by conventional vaccination procedures.
Assuntos
Senescência Celular/efeitos dos fármacos , Desidroepiandrosterona/farmacologia , Anticorpos Anti-Hepatite B/análise , Antígenos de Superfície da Hepatite B/administração & dosagem , Ativação Linfocitária , Linfocinas/biossíntese , Linfócitos T/efeitos dos fármacos , Adjuvantes Imunológicos/administração & dosagem , Animais , Senescência Celular/imunologia , Senescência Celular/fisiologia , Feminino , Antígenos de Superfície da Hepatite B/imunologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Ativação Linfocitária/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Fenótipo , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/fisiologia , VacinaçãoRESUMO
This review provides a scientific assessment of current knowledge of health effects of soybean oil (SBO) and sunflower oil (SFO). SBO and SFO both contain high levels of polyunsaturated fatty acids (PUFA) (60.8 and 69%, respectively), with a PUFA:saturated fat ratio of 4.0 for SBO and 6.4 for SFO. SFO contains 69% C18:2n-6 and less than 0.1% C18:3n-3, while SBO contains 54% C18:2n-6 and 7.2% C18:3n-3. Thus, SFO and SBO each provide adequate amounts of C18:2n-6, but of the two, SBO provides C18:3n-3 with a C18:2n-6:C18:3n-3 ratio of 7.1. Epidemiological evidence has suggested an inverse relationship between the consumption of diets high in vegetable fat and blood pressure, although clinical findings have been inconclusive. Recent dietary guidelines suggest the desirability of decreasing consumption of total and saturated fat and cholesterol, an objective that can be achieved by substituting such oils as SFO and SBO for animal fats. Such changes have consistently resulted in decreased total and low-density-lipoprotein cholesterol, which is thought to be favorable with respect to decreasing risk of cardiovascular disease. Also, decreases in high-density-lipoprotein cholesterol have raised some concern. Use of vegetable oils such as SFO and SBO increases C18:2n-6, decreases C20:4n-6, and slightly elevated C20:5n-3 and C22:6n-3 in platelets, changes that slightly inhibit platelet generation of thromboxane and ex vivo aggregation. Whether chronic use of these oils will effectively block thrombosis at sites of vascular injury, inhibit pathologic platelet vascular interactions associated with atherosclerosis, or reduce the incidence of acute vascular occlusion in the coronary or cerebral circulation is uncertain. Linoleic acid is needed for normal immune response, and essential fatty acid (EFA) deficiency impairs B and T cell-mediated responses. SBO and SFO can provide adequate linoleic acid for maintenance of the immune response. Excess linoleic acid has supported tumor growth in animals, an effect not verified by data from diverse human studies of risk, incidence, or progression of cancers of the breast and colon. Areas yet to be investigated include the differential effects of n-6- and n-3-containing oil on tumor development in humans and whether shorter-chain n-3 PUFA of plant origin such as found in SBO will modulate these actions of linoleic acid, as has been shown for the longer-chain n-3 PUFA of marine oils.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Gorduras Insaturadas na Dieta/farmacologia , Óleos de Plantas/farmacologia , Óleo de Soja/farmacologia , Animais , Plaquetas/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Gorduras Insaturadas na Dieta/efeitos adversos , Helianthus , Humanos , Imunidade/efeitos dos fármacos , Lipídeos/sangue , Neoplasias/etiologia , Neoplasias Experimentais/etiologia , Óleos de Plantas/efeitos adversos , Óleos de Plantas/química , Óleo de Soja/efeitos adversos , Óleo de Soja/química , Óleo de Girassol , Trombose/prevenção & controleRESUMO
Fifteen young (22-35 y) and 10 older (51-71 y) women received six capsules of fish oil (Pro-Mega)/d, providing a total of 1,680 mg eicosapentaenoic (EPA), 720 mg docosahexaenoic (DHA), 600 mg other fatty acids, and 6 IU vitamin E. Blood was collected before and after 1, 2 and 3 mo of supplementation. Compliance was confirmed by the significant increase in plasma EPA and DHA in all women. Older women had a significantly higher increase in EPA and DHA than did young women (10-fold increases in EPA and 2.5-fold increases in DHA vs. 8-fold in EPA and 2-fold in DHA for older and young women, respectively). The decrease in the arachidonic acid:EPA ratio was more dramatic in the older women. Plasma total triglycerides (TG) decreased significantly, and the ratio of polyunsaturated fatty acids to saturated fatty acids was significantly (P less than 0.01) increased. Plasma vitamin E levels did not change significantly after supplementation; however, after 3 mo of supplementation by young women, plasma vitamin E was significantly lower than after 1 mo. The vitamin E: TG ratio was significantly increased and vitamin E:(EPA + DHA) significantly decreased. All women showed a significant increase in plasma lipid peroxide through mo 2 of supplementation. After 2 mo, older women had significantly higher lipid peroxide levels than young women. The lipid peroxide:TG ratio, which declined by mo 3, was still significantly higher than baseline. These data indicate that although long-term fish oil supplementation may be beneficial in reducing plasma total TG, susceptibility of plasma lipids to free radical attack is potentiated.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Óleos de Peixe/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Vitamina E/sangue , Adulto , Fatores Etários , Idoso , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/sangue , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos/sangue , Feminino , Humanos , Peróxidos Lipídicos/sangue , Pessoa de Meia-Idade , Estatística como Assunto , Fatores de Tempo , Triglicerídeos/sangueRESUMO
The effect of (n-3) fatty acid supplementation on cytokine production and lymphocyte proliferation was investigated in young (23-33 y) and older (51-68 y) women. Subjects supplemented their diets with 2.4 g of (n-3) fatty acid/d for 3 mo. Blood was collected before and after 1, 2 and 3 mo of supplementation. The (n-3) fatty acid supplementation reduced total interleukin (IL)-1 beta synthesis by 48% in young women but by 90% in older women; tumor necrosis factor was reduced by 58% in young and 70% in older women. Interleukin-6 was reduced in young women by 30% but by 60% in older women. Older women produced less IL-2 and had lower mitogenic responses to phytohemagglutinin (PHA) than young women prior to (n-3) fatty acid supplementation. The (n-3) fatty acid supplementation reduced IL-2 production in both groups; however, this reduction was significant only in older women. The PHA-stimulated mitogenic response was significantly reduced by (n-3) fatty acid in older women (36%). Thus, long-term (n-3) fatty acid supplementation reduced cytokine production in young women and cytokine production and T cell mitogenesis in older women. The reduction was more dramatic in older women than in young women. Although (n-3) fatty acid-induced reduction in cytokine production may have beneficial anti-inflammatory effects, its suppression of IL-2 production and lymphocyte proliferation in older women may not be desirable.
Assuntos
Envelhecimento/metabolismo , Citocinas/biossíntese , Ácidos Graxos Ômega-3/farmacologia , Linfócitos T/citologia , Adulto , Idoso , Análise de Variância , Divisão Celular/efeitos dos fármacos , Dinoprostona/biossíntese , Ácidos Graxos/sangue , Feminino , Humanos , Interleucinas/biossíntese , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/biossíntese , Vitamina E/sangueRESUMO
This review of corn oil provides a scientific assessment of the current knowledge of its contribution to the American diet. Refined corn oil is composed of 99% triacylglycerols with polyunsaturated fatty acid (PUFA) 59%, monounsaturated fatty acid 24%, and saturated fatty acid (SFA) 13%. The PUFA is linoleic acid (C18:2n-6) primarily, with a small amount of linolenic acid (C18:3n-3) giving a n-6/n-3 ratio of 83. Corn oil contains a significant amount of ubiquinone and high amounts of alpha- and gamma-tocopherols (vitamin E) that protect it from oxidative rancidity. It has good sensory qualities for use as a salad and cooking oil. Corn oil is highly digestible and provides energy and essential fatty acids (EFA). Linoleic acid is a dietary essential that is necessary for integrity of the skin, cell membranes, the immune system, and for synthesis of icosanoids. Icosanoids are necessary for reproductive, cardiovascular, renal, and gastrointestinal functions and resistance to disease. Corn oil is a highly effective food oil for lowering serum cholesterol. Because of its low content of SFAs which raises cholesterol and its high content of PUFAs which lowers cholesterol, consumption of corn oil can replace SFAs with PUFAs, and the combination is more effective in lowering cholesterol than simple reduction of SFA. PUFA primarily lowers low-density-lipoprotein cholesterol (LDL-C) which is atherogenic. Research shows that PUFA has little effect on high-density-lipoprotein cholesterol (HDL-C) which is protective against atherosclerosis. PUFA generally improves the ratio of LDL-C to HDL-C. Studies in animals show that PUFA is required for the growth of cancers; the amount required is considered to be greater than that which satisfies the EFA requirement of the host. At this time there is no indication from epidemiological studies that PUFA intake is associated with increased risk of breast or colon cancer, which have been suggested to be promoted by high-fat diets in humans. Recommendations for minimum PUFA intake to prevent gross EFA deficiency are about 3% of energy (en%). Recommendations for prevention of heart disease are 8-10 en%. Consumption of PUFA in the United States is 5-7 en%. The use of corn oil to contribute to a PUFA intake of 10 en% in the diet would be beneficial to heart health. No single source of salad or cooking oil provides an optimum fatty acid (FA) composition. Many questions remain to be answered about the relation of FA composition of the diet to various physiological functions and disease processes.