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1.
Clin Nutr ESPEN ; 46: 394-404, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34857226

RESUMO

BACKGROUND & AIMS: The skeletal muscle anabolic effects of n-3 polyunsaturated fatty acids (n-3 PUFA) appear favoured towards women; a property that could be exploited in older women who typically exhibit poor muscle growth responses to resistance exercise training (RET). Here we sought to generate novel insights into the efficacy and mechanisms of n-3 PUFA alongside short-term RET in older women. METHODS: We recruited 16 healthy older women (Placebo n = 8 (PLA): 67±1y, n-3 PUFA n = 8: 64±1y) to a randomised double-blind placebo-controlled trial (n-3 PUFA; 3680 mg/day versus PLA) of 6 weeks fully-supervised progressive unilateral RET (i.e. 6 × 8 reps, 75% 1-RM, 3/wk-1). Strength was assessed by knee extensor 1-RM and isokinetic dynamometry âˆ¼ every 10 d. Thigh fat free mass (TFFM) was measured by DXA at 0/3/6 weeks. Bilateral vastus lateralis (VL) biopsies at 0/2/4/6 weeks with deuterium oxide (D2O) dosing were used to determine MPS responses for 0-2 and 4-6 weeks. Further, fibre cross sectional area (CSA), myonuclei number and satellite cell (SC) number were assessed, alongside muscle anabolic/catabolic signalling via immunoblotting. RESULTS: RET increased 1-RM equally in the trained leg of both groups (+23 ± 5% n-3 PUFA vs. +25 ± 5% PLA (both P < 0.01)) with no significant increase in maximum voluntary contraction (MVC) (+10 ± 6% n-3 PUFA vs. +13 ± 5% PLA). Only the n-3 PUFA group increased TFFM (3774 ± 158 g to 3961 ± 151 g n-3 PUFA (P < 0.05) vs. 3406 ± 201 g to 3561 ± 170 PLA) and type II fibre CSA (3097 ± 339 µm2 to 4329 ± 264 µm2 n-3 PUFA (P < 0.05) vs. 2520 ± 316 µm2 to 3467 ± 303 µm2 in PL) with RET. Myonuclei number increased equally in n-3 PUFA and PLA in both type I and type II fibres, with no change in SC number. N-3 PUFA had no added benefit on muscle protein synthesis (MPS), however, during weeks 4-6 of RET, absolute synthesis rates (ASR) displayed a trend to increase with n-3 PUFA only (5.6 ± 0.3 g d-1 to 7.1 ± 0.5 g d-1 n-3 PUFA (P = 0.09) vs. 5.5 ± 0.5 g d-1 to 6.5 ± 0.5 g d-1 PLA). Further, the n-3 PUFA group displayed greater 4EBP1 activation after acute RE at 6 weeks. CONCLUSION: n3-PUFA enhanced RET gains in muscle mass through type II fibre hypertrophy, with data suggesting a role for MPS rather than via SC recruitment. As such, the present study adds to a literature base illustrating the apparent enhancement of muscle hypertrophy with RET in older women fed adjuvant n3-PUFA.


Assuntos
Treinamento Resistido , Idoso , Suplementos Nutricionais , Exercício Físico , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas Musculares , Músculo Esquelético
2.
Clin Nutr ; 40(6): 4456-4464, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33487503

RESUMO

BACKGROUND & AIMS: Nutritional composition is key for skeletal muscle maintenance into older age. Yet the acute effects of collagen protein blended with other protein sources, in relation to skeletal muscle anabolism, are ill-defined. We investigated human muscle protein synthesis (MPS) responses to a 20 g blend of collagen protein hydrolysate + milk protein (CP+MP, 125 ml) oral nutritional supplement (ONS) vs. 20 g non-blended milk protein source (MP, 200 ml) ONS, in older adults. METHODS: Healthy older men (N = 8, 71±1 y, BMI: 27±1 kg·m-2) underwent a randomized trial of 20 g protein, from either a CP+MP blend (Fresubin®3.2 kcal DRINK), or a kcal-matched (higher in essential amino acids (EAA) ONS of MP alone. Vastus lateralis (VL) MPS and plasma AA were determined using stable isotope-tracer mass spectrometry; anabolic signaling was quantified via immuno-blotting in VL biopsies taken at baseline and 2/4 h after ONS feeding. Plasma insulin was measured via enzyme-linked immunosorbent assay (ELISA). Measures were taken at rest, after the feed (FED) and after the feed + exercise (FED-EX) conditions (unilateral leg exercise, 6 × 8, 75% 1-RM). RESULTS: MP resulted in a greater increase in plasma leucine (MP mean: 152 ± 6 µM, CP+MP mean: 113 ± 4 µM (Feed P < 0.001) and EAA (MP mean: 917 ± 25 µM, CP+MP mean: 786 ± 15 µM (Feed P < 0.01) than CP+MP. CP + MP increased plasma glycine (peak 385 ± 57 µM (P < 0.05)), proline (peak 323 ± 29 µM (P < 0.01)) and non-essential amino acids (NEAA) (peak 1621 ± 107 µM (P < 0.01)) with MP showing no increase. Plasma insulin increased in both trials (CP+MP: 58 ± 10 mU/mL (P < 0.01), MP: 42 ± 6 mU/mL (P < 0.01), with peak insulin greater with CP+MP vs. MP (P < 0.01). MPS demonstrated equivalent increases in response to CP+MP and MP under both FED (MP: 0.039 ± 0.005%/h to 0.081 ± 0.014%/h (P < 0.05), CP+MP: 0.042 ± 0.004%/h to 0.085 ± 0.007%/h (P < 0.05)) and FED-EX (MP: 0.039 ± 0.005%/h to 0.093 ± 0.013%/h (P < 0.01), CP+MP: 0.042 ± 0.004%/h to 0.105 ± 0.015%/h, (P < 0.01)) conditions. FED muscle p-mTOR fold-change from baseline increased to a greater extent with CP+MP vs. MP (P < 0.05), whilst FED-EX muscle p-eEF2 fold-change from baseline decreased to a greater extent with CP+MP vs. MP (P < 0.05); otherwise anabolic signaling responses were indistinguishable. CONCLUSION: Fresubin®3.2 kcal DRINK, which contains a 20 g mixed blend of CP+MP, resulted in equivalent MPS responses to MP alone. Fresubin® 3.2 Kcal DRINK may provide a suitable alternative to MP for use in older adults and a convenient way to supplement calories and protein to improve patient adherence and mitigate muscle mass loss.


Assuntos
Aminoácidos Essenciais/análise , Colágeno , Suplementos Nutricionais , Alimentos Formulados , Proteínas do Leite , Proteínas Musculares/biossíntese , Hidrolisados de Proteína , Idoso , Aminoácidos/sangue , Estudos Cross-Over , Alimentos Formulados/análise , Humanos , Insulina/sangue , Masculino , Proteínas do Leite/análise , Músculo Esquelético/metabolismo , Transdução de Sinais
3.
Clin Nutr ; 38(5): 2071-2078, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30360984

RESUMO

Age-related sarcopenia and dynapenia are associated with frailty and metabolic diseases. Resistance exercise training (RET) adjuvant to evidence-based nutritional intervention(s) have been shown as mitigating strategies. Given that ß-hydroxy-ß-methyl-butyrate (HMB) supplementation during RET improves lean body mass in younger humans, and that we have shown that HMB acutely stimulates muscle protein synthesis (MPS) and inhibits breakdown; we hypothesized that chronic supplementation of HMB free acid (HMB-FA) would enhance MPS and muscle mass/function in response to RET in older people. We recruited 16 healthy older men (Placebo (PLA): 68.5 ± 1.0 y, HMB-FA: 67.8 ± 1.15 y) for a randomised double-blind-placebo controlled trial (HMB-FA 3 × 1 g/day vs. PLA) involving a 6-week unilateral progressive RET regime (6 × 8 repetitions, 75% 1-RM, 3 · wk-1). Deuterium oxide (D2O) dosing was performed over the first two weeks (0-2 wk) and last two weeks (4-6 wk) with bilateral vastus lateralis (VL) biopsies at 0-2 and 4-6 wk (each time 75 ± 2 min after a single bout of resistance exercise (RE)) for quantification of early and later MPS responses and post-RE myogenic gene expression. Thigh lean mass (TLM) was measured by DXA, VL thickness and architecture (fibre length and pennation angle) by ultrasound at 0/3/6 wk, and strength by knee extensor 1-RM testing and MVC by isokinetic dynamometry (approx. every 10 days). RET induced strength increases (1-RM) in the exercised leg of both groups (398 ± 22N to 499 ± 30N HMB-FA vs. 396 ± 29N to 510 ± 43N PLA (both P < 0.05)). In addition, maximal voluntary contraction (MVC) also increased (179 ± 12 Nm to 203 ± 12 Nm HMB-FA vs. 185 ± 10 Nm to 217 ± 11 Nm PLA (both P < 0.05); with no group differences. VL muscle thickness increased significantly in the exercised leg in both groups, with no group differences. TLM (by DXA) rose to significance only in the HMB-FA group (by 5.8%-5734 ± 245 g p = 0.015 vs. 3.0% to 5644 ± 323 g P = 0.06 in PLA). MPS remained unchanged in the untrained legs (UT) 0-2 weeks being 1.06 ± 0.08%.d-1 (HMB-FA) and 1.14 ± 0.09%.d-1 (PLA), the trained legs (T) exhibited increased MPS in the HMB-FA group only at 0-2-weeks (1.39 ± 0.10%.d-1, P < 0.05) compared with UT: but was not different at 4-6-weeks: 1.26 ± 0.05%.d-1. However, there were no significant differences in MPS between the HMB-FA and PLA groups at any given time point and no significant treatment interaction observed. We also observed significant inductions of c-Myc gene expression following each acute RE bout, with no group differences. Further, there were no changes in any other muscle atrophy/hypertrophy or myogenic transcription factor genes we measured. RET with adjuvant HMB-FA supplements in free-living healthy older men did not enhance muscle strength or mass greater than that of RET alone (PLA). That said, only HMB-FA increased TLM, supported by early increases in chronic MPS. As such, chronic HMB-FA supplementation may result in long term benefits in older males, however longer and larger studies may be needed to fully determine the potential effects of HMB-FA supplementation; translating to any functional benefit.


Assuntos
Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Treinamento Resistido , Valeratos , Suplementos Nutricionais , Método Duplo-Cego , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Desenvolvimento Muscular/efeitos dos fármacos , Desenvolvimento Muscular/genética , Biossíntese de Proteínas/efeitos dos fármacos , Valeratos/administração & dosagem , Valeratos/sangue , Valeratos/farmacologia
4.
Clin Nutr ; 37(6 Pt A): 2068-2075, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29097038

RESUMO

BACKGROUND & AIMS: ß-hydroxy-ß-methylbutyrate (HMB) is purported as a key nutritional supplement for the preservation of muscle mass in health, disease and as an ergogenic aid in exercise. Of the two available forms of HMB (calcium (Ca-HMB) salt or free acid (FA-HMB)) - differences in plasma bioavailability have been reported. We previously reported that ∼3 g oral FA-HMB increased muscle protein synthesis (MPS) and reduced muscle protein breakdown (MPB). The objective of the present study was to quantify muscle protein metabolism responses to oral Ca-HMB. METHODS: Eight healthy young males received a primed constant infusion of 1,2 13C2 leucine and 2H5 phenylalanine to assess MPS (by tracer incorporation in myofibrils) and MPB (via arterio-venous (A-V) dilution) at baseline and following provision of ∼3 g of Ca-HMB; muscle anabolic (MPS) and catabolic (MPB) signalling was assessed via immunoblotting. RESULTS: Ca-HMB led a significant and rapid (<60 min) peak in plasma HMB concentrations (483.6 ± 14.2 µM, p < 0.0001). This rise in plasma HMB was accompanied by increases in MPS (PA: 0.046 ± 0.004%/h, CaHMB: 0.072 ± 0.004%/h, p < 0001) and suppressions in MPB (PA: 7.6 ± 1.2 µmol Phe per leg min-1, Ca-HMB: 5.2 ± 0.8 µmol Phe per leg min-1, p < 0.01). Increases in the phosphorylation of mTORc1 substrates i.e. p70S6K1 and RPS6 were also observed, with no changes detected in the MPB targets measured. CONCLUSIONS: These findings support the pro-anabolic properties of HMB via mTORc1, and show that despite proposed differences in bioavailability, Ca-HMB provides a comparable stimulation to MPS and suppression of MPB, to FA-HMB, further supporting its use as a pharmaconutrient in the modulation of muscle mass.


Assuntos
Cálcio/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Valeratos/metabolismo , Adulto , Disponibilidade Biológica , Cálcio/farmacocinética , Sinalização do Cálcio , Suplementos Nutricionais , Humanos , Masculino , Proteínas Musculares/química , Músculo Esquelético/química , Valeratos/farmacocinética , Adulto Jovem
5.
Acta Physiol (Oxf) ; 216(1): 15-41, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26010896

RESUMO

Skeletal muscles comprise a substantial portion of whole body mass and are integral for locomotion and metabolic health. Increasing age is associated with declines in both muscle mass and function (e.g. strength-related performance, power) with declines in muscle function quantitatively outweighing those in muscle volume. The mechanisms behind these declines are multi-faceted involving both intrinsic age-related metabolic dysregulation and environmental influences such as nutritional and physical activity. Ageing is associated with a degree of 'anabolic resistance' to these key environmental inputs, which likely accelerates the intrinsic processes driving ageing. On this basis, strategies to sensitize and/or promote anabolic responses to nutrition and physical activity are likely to be imperative in alleviating the progression and trajectory of sarcopenia. Both resistance- and aerobic-type exercises are likely to confer functional and health benefits in older age, and a clutch of research suggests that enhancement of anabolic responsiveness to exercise and/or nutrition may be achieved by optimizing modifications of muscle-loading paradigms (workload, volume, blood flow restriction) or nutritional support (e.g. essential amino acid/leucine) patterns. Nonetheless, more work is needed in which a more holistic view in ageing studies is taken into account. This should include improved characterization of older study recruits, that is physical activity/nutritional behaviours, to limit confounding variables influencing whether findings are attributable to age, or other environmental influences. Nonetheless, on balance, ageing is associated with declines in muscle mass and function and a partially related decline in aerobic capacity. There is also good evidence that metabolic flexibility is impaired in older age.


Assuntos
Envelhecimento/fisiologia , Exercício Físico/fisiologia , Homeostase/fisiologia , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Animais , Humanos , Estado Nutricional/fisiologia
6.
J Vet Intern Med ; 26(3): 598-607, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22390318

RESUMO

BACKGROUND: Effective treatments for dogs with advanced stage mast cell tumors (MCT) remain a pressing need. A micellar formulation of paclitaxel (paclitaxel [micellar]) has shown promise in early-phase studies. HYPOTHESIS/OBJECTIVES: The objective was to demonstrate greater activity for paclitaxel (micellar) compared with lomustine. The null hypothesis was µ(p) = µ(L) (ie, proportion of responders for the paclitaxel [micellar] and lomustine groups, respectively). ANIMALS: Two hundred and fifty-two dogs with advanced stage nonresectable grade 2 or 3 MCT. METHODS: Prospective multicenter randomized double-blind positive-controlled clinical trial. The primary endpoint was confirmed overall response rate (CORR) at 14 weeks. A secondary endpoint, biologic observed response rate (BORR), also was calculated. Safety was assessed by the characterization and grading of adverse events (AE). RESULTS: Overall CORR (7% versus 1%; P = .048) and BORR (23% versus 10%; P = .012) were greater for paclitaxel (micellar) compared with lomustine. Paclitaxel (micellar)-treated dogs were 6.5 times more likely to have a confirmed response and 3.1 times more likely to experience a biologic observed response. The majority of AE with paclitaxel (micellar) were transient and clinically manageable. Twenty-seven dogs (33%) receiving lomustine were discontinued because of hepatopathy compared with 3 dogs (2%) receiving paclitaxel (micellar) (P < .0001; odds ratio 26.7). CONCLUSIONS AND CLINICAL IMPORTANCE: Paclitaxel (micellar)'s activity and safety profile are superior to lomustine. The addition of an active and novel taxane to the veterinary armamentarium could fill a substantial need and, as its mechanism of action and AE profile do not overlap with currently available TKI, its availability could lead to effective combination protocols.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Sarcoma de Mastócitos/veterinária , Micelas , Paclitaxel/uso terapêutico , Animais , Antineoplásicos Fitogênicos/química , Doenças do Cão/patologia , Cães , Método Duplo-Cego , Feminino , Masculino , Sarcoma de Mastócitos/tratamento farmacológico , Paclitaxel/química , Estudos Prospectivos , Estatísticas não Paramétricas , Resultado do Tratamento
7.
Phytomedicine ; 10(4): 325-33, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12809363

RESUMO

Over four-hundred crude extracts from 202 plant species distributed among 131 plant families were evaluated for their bioactivity against brine shrimp (Artemia salina). Activity was determined for both the organic (CH2Cl2:MeOH) and aqueous extracts against A. salina in a 96 well-plate assay. Of the greater than four-hundred extracts tested, 21 organic and 6 aqueous extracts demonstrated potent cytotoxic activity (LC50 = < 100 microg/ml). Three of these organic extracts (Crateva religiosa, Diospyros dichrophylla, and Olax subscorpioidea) were chosen for chemical investigations due to their high activity and a lack of prior investigations. Chemical analysis of these extracts resulted in the isolation of oleanolic acid (1) and 4-epi-hederagenin (2) from C. religiosa, isodiospyrin (3) from D. dichrophylla, and santalbic acid (4) from O. subscorpioidea.


Assuntos
Fitoterapia , Extratos Vegetais/farmacologia , Plantas Medicinais , Animais , Artemia/efeitos dos fármacos , Capparaceae , Diospyros , Dose Letal Mediana , Olacaceae , Sementes
8.
Biochem Biophys Res Commun ; 284(2): 478-84, 2001 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-11394905

RESUMO

Embryonic stem (ES) cells have the capacity to differentiate into various cell types in vitro. In this study, we show that retinoic acid is important for the commitment of ES cells into osteoblasts. Culturing retinoic acid treated ES cells in the presence of the osteogenic supplements ascorbic acid and beta-glycerophosphate resulted in the expression of several osteoblast marker genes, osteocalcin, alkaline phosphatase, and osteopontin. However, there was only a slight amount of mineralized matrix secretion. Addition of bone morphogenic protein-2 or compactin, a drug of the statin family of HMG-CoA reductase inhibitors, resulted in a greatly enhanced formation of bone nodules. Compactin did not modify the expression of osteogenic markers, but at the late stage of differentiation promoted an increase in BMP-2 expression. These results establish ES-cell derived osteogenesis as an effective model system to study the molecular mechanisms by which the statin compactin promotes osteoblastic differentiation and bone nodule formation.


Assuntos
Proteínas Morfogenéticas Ósseas/farmacologia , Diferenciação Celular/efeitos dos fármacos , Lovastatina/análogos & derivados , Lovastatina/farmacologia , Osteogênese/efeitos dos fármacos , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Antígenos de Diferenciação/biossíntese , Antígenos de Diferenciação/genética , Ácido Ascórbico/farmacologia , Proteína Morfogenética Óssea 2 , Células Cultivadas , Glicerofosfatos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Camundongos , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteocalcina/biossíntese , Osteocalcina/genética , Osteopontina , RNA Mensageiro/metabolismo , Sialoglicoproteínas/biossíntese , Sialoglicoproteínas/genética , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Tretinoína/farmacologia
11.
J Am Osteopath Assoc ; 97(11): 686-91, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9397653

RESUMO

In July 1995, the American Osteopathic Association (AOA) Board of Trustees passed new regulations regarding the accreditation of osteopathic graduate medical education (GME) by establishing the Osteopathic Postdoctoral Training Institutions (OPTI) system. This system must be phased in by July 1999. The principal changes resulting from the OPTI system include establishing requirements for college cosponsorship of GME programs and for the number of residency programs, interns, and residents to be trained by the OPTI. In essence, OPTI is an osteopathic acronym for consortium. Each OPTI must include at least one college of osteopathic medicine (COM) and one AOA-accredited hospital. The OPTIs will be subject to interval AOA inspections and will be required to demonstrate a governing system, mission statement, organizational structure, and the presence of faculty development programs. The first article in this two-part series, published in the October JAOA, provided a general blueprint for OPTI building and presented both positive and negative issues germane to the formation of OPTIs. Part 2 reinforces the considerations outlined in Part 1 by describing the formation of a large OPTI--the Ohio University College of Osteopathic Medicine (OU-COM) Centers of Osteopathic Regional Education (CORE) system. Key features are described, including the mission statement, organizational structure, committee system, governance, GME programs, operations, and budget.


Assuntos
Acreditação/normas , Educação de Pós-Graduação em Medicina/normas , Medicina Osteopática/educação , Acreditação/legislação & jurisprudência , Educação de Pós-Graduação em Medicina/legislação & jurisprudência , Guias como Assunto , Humanos , Internato e Residência/organização & administração , Internato e Residência/normas , Ohio , Medicina Osteopática/normas , Avaliação de Programas e Projetos de Saúde , Sociedades Médicas
12.
Pharm Pract Manag Q ; 17(3): 21-31, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10173308

RESUMO

Metformin and acarbose are novel antihyperglycemic agents indicated for the treatment of non-insulin-dependent diabetes mellitus. These agents offer new therapeutic options to control hyperglycemia that were previously unavailable. Common to both agents is a relatively high incidence of gastrointestinal adverse effects. Initiating therapy at a low dose and slowly titrating to therapeutic response may be the most effective way to minimize associated adverse effects. Recognition and proper management of these possible adverse effects can optimize therapy and maximize the potential for successful outcomes with these agents while limiting drug noncompliance.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Gerenciamento Clínico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Resultado do Tratamento , Trissacarídeos/uso terapêutico , Acarbose , Humanos , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Trissacarídeos/efeitos adversos , Estados Unidos
13.
Environ Mol Mutagen ; 30(2): 161-74, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9329641

RESUMO

A human volunteer study was conducted to test the effect of vitamin C supplementation on biomarkers of oxygen radical-mediated damage in individuals with a range of serum cholesterol levels. A group of 48 non-smokers, 24 men and 24 women, was selected from a panel of over 100 volunteers to give as wide a range of serum cholesterol levels as possible. None of the volunteers was taking medication to control cholesterol levels and they maintained their normal dietary habits so as not to compromise their cholesterol status. Volunteers were allocated to three groups of 16, each consisting of four males with low cholesterol levels (< 6 mmol/L) matched for age and build with four males with high cholesterol levels (> 6 mmol/L) and eight females matched in the same way. A three-treatment, three-treatment period, cross-over design was adopted to take account of any temporal differences in response. The three treatments given were placebo, 60 mg vitamin C/day (the recommended daily allowance) and 6 g vitamin C/day. Each treatment was given for 14 days with 6 weeks between the treatment periods. All procedures were performed to the standards of Good Clinical Practice. Blood samples were taken at the end of each treatment period. Serum was assayed for cholesterol whilst vitamin C, total antioxidant capacity, lipid peroxidation breakdown products and ras p21 protein levels were measured in plasma. Lymphocytes were examined for DNA damage using the Comet assay and chromosome aberration test. The Comet assay was conducted with and without challenge with hydrogen peroxide and the chromosome aberration test with and without challenge with bleomycin. Vitamin C supplementation caused a statistically significant increase in plasma vitamin C concentrations and total antioxidant capacity but did not affect cholesterol levels or ras p21 protein levels. There was a non-significant dose-related decrease in lipid peroxidation breakdown products with vitamin C supplementation. No effect on DNA damage was observed in the Comet assay, either with or without hydrogen peroxide challenge, or in the chromosome aberration test without bleomycin. However, a statistically significant increase in bleomycin-induced aberrations was found after vitamin C supplementation. This may be due to effects of vitamin C on iron status. Comparison of male and female subjects showed statistically significant differences in plasma vitamin C levels, the antioxidant capacity of the plasma and the number of chromosome aberrations induced by bleomycin challenge of lymphocytes in vitro. The results were the same for both low and high cholesterol subjects. This study provides no evidence of a beneficial effect on any of the biomarkers studied of vitamin C supplementation over a short-term supplementation period of 2 weeks in a population of healthy, non-smoking individuals eating a nutritionally adequate diet.


Assuntos
Ácido Ascórbico/uso terapêutico , Colesterol/sangue , Dano ao DNA , Oxigênio/metabolismo , Adulto , Idoso , Antioxidantes/metabolismo , Ácido Ascórbico/sangue , Bleomicina/farmacologia , Aberrações Cromossômicas , Relação Dose-Resposta a Droga , Feminino , Radicais Livres , Técnicas Genéticas , Humanos , Peroxidação de Lipídeos , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas p21(ras)/sangue , Proteínas Proto-Oncogênicas p21(ras)/efeitos dos fármacos
14.
Food Chem Toxicol ; 34(5): 439-48, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8655092

RESUMO

Eating green potatoes has reportedly led to poisoning attributed to potato glycoalkaloids (PGA), primarily alpha-solanine and alpha-chaconine. Concentrations of PGA increase during the greening of potatoes but are reportedly much higher in potato tops (leaves). As it is known that members of the UK Bangladeshi community consume potato tops, a study of the toxic hazard that may be associated with the consumption of green potato tops has been carried out. PGA in seven potato varieties were determined by HPLC. Tubers protected from light contained 0.05-0.65 mg/100 g alpha-solanine and 0.3-0.63 mg/100 g alpha-chaconine. Concentrations in leaf samples ranged from 0.64 to 22.6 mg alpha-solanine/100 g and 0.06 to 55.7 mg alpha-chaconine/100 g. Aqueous leaf extracts were cytotoxic to Chinese hamster ovary cells and lysed human, rat and hamster blood cells with no difference in sensitivity among species. Oral administration of potato tops to rats, mice and Syrian hamsters had no adverse effects at the highest practicable dose. A mixture of alpha-solanine and alpha-chaconine (1:1, w/w) given orally at doses of up to 50 mg/kg body weight to hamsters had no effect, but a single ip injection of 25 mg/kg body weight or greater was lethal, with bleeding in the gut. High concentrations of cytotoxic PGA were found in some potato tops, but their effect in laboratory animals was minimal. It is concluded that the consumption of moderate quantities of potato tops (2-5 g/kg body weight/day) is unlikely to represent an acute health hazard to humans.


Assuntos
Solanina/análogos & derivados , Solanina/toxicidade , Solanum tuberosum/toxicidade , Animais , Células Sanguíneas/efeitos dos fármacos , Células CHO/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Cricetinae , Humanos , Masculino , Camundongos , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley , Solanum tuberosum/química
17.
Artigo em Inglês | MEDLINE | ID: mdl-8428129

RESUMO

A retrospective study of 14 patients with epileptic seizures and 11 with nonepileptic seizures, all taking antiepileptic drugs, found epileptic patients had significantly longer P160, N200, and P300 latencies on auditory event-related potential recordings. Patients with nonepileptic seizures had generally higher IQs and significantly greater psychopathology on neuropsychological scales.


Assuntos
Epilepsia Tipo Ausência/diagnóstico , Epilepsia/diagnóstico , Estimulação Acústica , Adulto , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Potenciais Evocados Auditivos , Feminino , Humanos , Inteligência , MMPI , Masculino , Estudos Retrospectivos , Escalas de Wechsler
19.
Chest ; 95(2): 299-303, 1989 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2914478

RESUMO

We evaluated the safety and efficacy of high-dose topical and nebulized airway anesthesia in normal volunteers and in patients undergoing diagnostic fiberoptic bronchoscopy. Lidocaine solution (4 percent) was used for gargling, for spraying the palate and oropharynx with an atomizer, and for nebulization with an air-powered nebulizer (mean total dose, 1,682 mg) and 2 percent lidocaine (Xylocaine) jelly for anesthetizing nasal passages. In six normal subjects and in eight patients, lidocaine blood levels were measured at baseline, after gargling, after spraying, after nebulization, and then at 5, 10, 15, 30, and 60 min; 19 normal subjects and ten patients underwent the same anesthesia protocol but had no blood drawn. Fiberoptic bronchoscopy was performed in 21 normal volunteers and in 18 patients and cultures obtained using the protected specimen brush. Additional endobronchial lidocaine (mean 256 mg) was given to the 18 patients after collecting the microbiology specimens. Peak lidocaine blood levels remained below 6 micrograms/ml in all cases. Cough and discomfort during bronchoscopic examination was absent or minimal in 17 of 21 normal subjects (80 percent) and in 14 of 18 patients (77 percent) and was severe in only one instance (5 percent). There were no related complications. Using only topical and nebulized anesthesia is safe and effective for performing fiberoptic bronchoscopy, especially when bacterial cultures are to be obtained and endobronchial instillation of lidocaine must be avoided.


Assuntos
Anestesia Local/métodos , Brônquios/microbiologia , Broncoscopia , Lidocaína/administração & dosagem , Adolescente , Adulto , Anestesia Local/efeitos adversos , Feminino , Humanos , Lidocaína/sangue , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores
20.
Pediatrics ; 80(5): 680-3, 1987 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3670969

RESUMO

Serum vitamin E levels were measured in 19 infants weighing 1.0 to 1.5 kg, in 16 infants weighing less than 1 kg who received 65% of a vial (4.6 mg of vitamin E) of multivitamins (MVI Pediatric) daily, and in another group of 16 infants weighing less than 1 kg who received 30% of a vial (2.1 mg of vitamin E) daily. Supplementation was started within 12 hours of birth. Serum vitamin E levels were also measured after supplementation was discontinued in infants who had received 65% of a vial daily. Vitamin E sufficiency (levels equal to or greater than 0.5 mg/dL) was attained after 48 hours of supplementation in all infants receiving 65% of a vial daily and after 72 hours of supplementation in all infants receiving 30% of a vial daily. Vitamin E sufficiency was not maintained in all infants receiving 30% of a vial daily. Of the infants weighing less than 1 kg who received 65% of a vial daily, 31% had serum levels greater than 3.5 mg/dL, whereas no infant weighing less than 1 kg who received 30% of a vial daily had a level greater than 3.5 mg/dL (P less than .05). Of the infants weighing less than 1 kg who received 30% of a vial daily, 56% had levels less than 1 mg/dL v 6% of infants less than 1 kg who received 65% of a vial daily (P less than .01). Vitamin E levels decreased after MVI Pediatric supplementation with 65% of a vial was discontinued (P less than .05). After MVI Pediatric was discontinued, some infants became vitamin E insufficient.


Assuntos
Recém-Nascido Prematuro/sangue , Vitamina E/sangue , Humanos , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Fatores de Tempo , Vitamina E/administração & dosagem
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