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1.
Artigo em Inglês | MEDLINE | ID: mdl-38771662

RESUMO

This essay builds on the exciting trove of disaster social science research surfacing since the earliest days of the COVID-19 pandemic. It tracks the ways that both practitioners of medicine and public health, and their social science analogues, have approached the pandemic, explicitly considering the ways they reached for new concepts to explain the temporal phenomena presented by COVID-19 and its global course. The essay highlights a series of interviews conducted in the first two years of the pandemic as part of the COVIDCalls podcast. COVID is the moment for a scholarly convergence that was missed after September 11, and again after Hurricane Katrina, and should not be missed again. Accordingly, this essay explores themes where medicine/health studies and disaster studies seem to offer great help to one another in making sense of our COVID times: the origins of disaster, disasters in combination, and the end of a disaster.

2.
Cell ; 135(3): 437-48, 2008 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-18984156

RESUMO

Interactions between tumorigenic cells and their surrounding microenvironment are critical for tumor progression yet remain incompletely understood. Germline mutations in the NF1 tumor suppressor gene cause neurofibromatosis type 1 (NF1), a common genetic disorder characterized by complex tumors called neurofibromas. Genetic studies indicate that biallelic loss of Nf1 is required in the tumorigenic cell of origin in the embryonic Schwann cell lineage. However, in the physiologic state, Schwann cell loss of heterozygosity is not sufficient for neurofibroma formation and Nf1 haploinsufficiency in at least one additional nonneoplastic lineage is required for tumor progression. Here, we establish that Nf1 heterozygosity of bone marrow-derived cells in the tumor microenvironment is sufficient to allow neurofibroma progression in the context of Schwann cell Nf1 deficiency. Further, genetic or pharmacologic attenuation of c-kit signaling in Nf1+/- hematopoietic cells diminishes neurofibroma initiation and progression. Finally, these studies implicate mast cells as critical mediators of tumor initiation.


Assuntos
Neurofibroma/metabolismo , Neurofibromina 1/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Animais , Benzamidas , Medula Óssea/fisiopatologia , Transplante de Medula Óssea , Pré-Escolar , Genes da Neurofibromatose 1 , Humanos , Mesilato de Imatinib , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurofibroma/tratamento farmacológico , Neurofibroma/genética , Neurofibroma/patologia , Neurofibroma Plexiforme/tratamento farmacológico , Neurofibroma Plexiforme/metabolismo , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Células de Schwann/metabolismo
3.
Proc Natl Acad Sci U S A ; 111(3): 1108-13, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-24390540

RESUMO

The noninvasive detection and quantification of CD8(+) T cells in vivo are important for both the detection and staging of CD8(+) lymphomas and for the monitoring of successful cancer immunotherapies, such as adoptive cell transfer and antibody-based immunotherapeutics. Here, antibody fragments are constructed to target murine CD8 to obtain rapid, high-contrast immuno-positron emission tomography (immuno-PET) images for the detection of CD8 expression in vivo. The variable regions of two anti-murine CD8-depleting antibodies (clones 2.43 and YTS169.4.2.1) were sequenced and reformatted into minibody (Mb) fragments (scFv-CH3). After production and purification, the Mbs retained their antigen specificity and bound primary CD8(+) T cells from the thymus, spleen, lymph nodes, and peripheral blood. Importantly, engineering of the parental antibodies into Mbs abolished the ability to deplete CD8(+) T cells in vivo. The Mbs were subsequently conjugated to S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid for (64)Cu radiolabeling. The radiotracers were injected i.v. into antigen-positive, antigen-negative, immunodeficient, antigen-blocked, and antigen-depleted mice to evaluate specificity of uptake in lymphoid tissues by immuno-PET imaging and ex vivo biodistribution. Both (64)Cu-radiolabeled Mbs produced high-contrast immuno-PET images 4 h postinjection and showed specific uptake in the spleen and lymph nodes of antigen-positive mice.


Assuntos
Anticorpos Monoclonais/imunologia , Linfócitos T CD8-Positivos/citologia , Fragmentos de Imunoglobulinas/imunologia , Tomografia por Emissão de Pósitrons , Alelos , Animais , Especificidade de Anticorpos/imunologia , Antígenos/química , Radioisótopos de Cobre/química , Epitopos/química , Citometria de Fluxo , Imunoterapia/métodos , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos SCID , Ratos , Distribuição Tecidual
4.
N Z Vet J ; 70(5): 245-247, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35762148
6.
J Food Sci Technol ; 53(11): 4033-4042, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28035159

RESUMO

Conventional gnocchi are small Italian dumplings made from potatoes, flour, and eggs. In this study, a range of gnocchi-type products containing navy bean and beef meat (10-40% w/w) were developed. The nutritional, physicochemical and sensory properties of the formulated gnocchi were determined, and a Modified in vitro Stomach Stir Tank (MISST) system was used to determine in vitro digestibility. Adding meat significantly increased the fat and protein content of cooked gnocchi type products compared to the control sample. Addition of navy bean and meat also significantly increased hardness, springiness, and chewiness, of most gnocchi type products compared to control sample. In vitro studies showed that pH increased faster in samples high in meat and navy bean content during the initial 30 min to control. The addition of high levels of meat emulsion and navy bean increased, springiness, beany, and meaty flavour. Gnocchi with 20% meat emulsion was similar to control upto some extent being characterized to have flocculent, soft, chewy, and wheaty in flavour. The addition of meat and navy bean did not affect the digestibility of starch in the gastrointestinal tract. Fortified gnocchi with meat and bean was showed a promising vehicle to deliver nutritive values without any changes in starch digestibility.

7.
Curr Oncol ; 31(5): 2598-2609, 2024 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-38785476

RESUMO

Brentuximab vedotin (BV) monotherapy (BV-M) and combination (BV-C) therapies are safe and effective for classical Hodgkin lymphoma (cHL) and CD30-expressing peripheral T-cell lymphomas (PTCLs). Although the sample sizes have been small (12-29 patients), in clinical studies, response rates of 53-88% have been reported for BV retreatment in patients with an initial BV response. We evaluated the real-world characteristics and treatment patterns of cHL/PTCL patients who received BV and were retreated in the United States. Symphony Health Patient Claims (11/2013-1/2022) were retrospectively analyzed to identify cHL/PTCL patients treated with BV and retreated with BV-M, BV-C, or non-BV therapy. Patient characteristics were described by retreatment, and predictors of BV-M retreatment were identified. Among the cHL and PTCL patients treated with BV (n = 6442 and 2472, respectively), 13% and 12%, respectively, were retreated with BV; the median times from initial BV to BV-M retreatment were 5 and 7 months, respectively; and the numbers of BV-M retreatment doses were 4 and 5, respectively. Among cHL patients, the predictors of BV-M retreatment were age (18-39 vs. ≥60 years), sex (women vs. men), and previous stem cell transplantation (yes vs. no). Among PTCL patients, the only predictor of BV-M retreatment was systemic anaplastic large-cell lymphoma subtype (yes vs. no). Real-world data support clinical study results suggesting earlier BV treatment be considered, as BV retreatment may be an option.


Assuntos
Brentuximab Vedotin , Doença de Hodgkin , Linfoma de Células T Periférico , Humanos , Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Linfoma de Células T Periférico/tratamento farmacológico , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Estados Unidos , Adulto Jovem , Idoso , Retratamento , Adolescente , Antineoplásicos Imunológicos/uso terapêutico
8.
Biomacromolecules ; 14(5): 1458-64, 2013 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-23581747

RESUMO

Block polypeptides are an emerging class of materials that have the potential to be used in many biomedical applications, including the field of drug delivery. We have previously developed a negatively charged block copolypeptide, poly(L-glutamate)60-b-poly(L-leucine)20 (E60L20), which forms spherical vesicles in aqueous solution. Since these vesicles are negatively charged, they are minimally toxic toward cells. However, the negative charge also inhibits these vesicles from effectively being internalized by cells, which can be problematic as many therapeutics have intracellular targets. To overcome this limitation of the E60L20 vesicles, transferrin (Tf) was conjugated onto the vesicle surface, since the receptor for Tf is overexpressed on cancer cells. The enhanced uptake of the Tf-conjugated vesicle was verified through confocal microscopy. Furthermore, endocytosis and immunostaining experiments confirmed that the Tf conjugated on the vesicle surface plays a critical role in the internalization and subsequent intracellular trafficking behavior of the vesicles.


Assuntos
Portadores de Fármacos/síntese química , Endocitose , Peptídeos/química , Ácido Poliglutâmico/análogos & derivados , Transferrina/química , Transporte Biológico , Linhagem Celular Tumoral , Portadores de Fármacos/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Humanos , Microscopia Confocal , Peptídeos/metabolismo , Ácido Poliglutâmico/metabolismo , Receptores da Transferrina/metabolismo , Eletricidade Estática , Transferrina/metabolismo , Água
9.
Front Nutr ; 10: 1174726, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37388633

RESUMO

Background: Flexitarian, vegetarian and exclusively plant-based diets are increasingly popular, particularly amongst young adults. This is the first randomised dietary intervention to investigate the health, wellbeing, and behavioural implications of consuming a basal vegetarian diet that additionally includes low-to-moderate amounts of red meat (flexitarian) compared to one containing plant-based meat alternatives (PBMAs, vegetarian) in young adults (ClinicalTrials.gov NCT04869163). The objective for the current analysis is to measure adherence to the intervention, nutrition behaviours, and participants' experience with their allocated dietary group. Methods: Eighty healthy young adults participated in this 10-week dietary intervention as household pairs. Household pairs were randomised to receive either approximately three serves of red meat (average of 390 g cooked weight per individual, flexitarian group) or PBMAs (350-400 g per individual, vegetarian group) per week on top of a basal vegetarian diet. Participants were supported to adopt healthy eating behaviours, and this intervention was developed and implemented using a behaviour change framework. Adherence (eating allocated red meat or PBMA, abstaining from animal-based foods not provided by researchers) was continuously monitored, with total scores calculated at the end of the 10-week intervention period. Eating experiences were measured by the Positive Eating Scale and a purpose-designed exit survey, and a food frequency questionnaire measured dietary intake. Analyses used mixed effects modeling taking household clustering into account. Results: The total average adherence score was 91.5 (SD = 9.0) out of a possible 100, with participants in the flexitarian group scoring higher (96.1, SD = 4.6, compared to 86.7, SD = 10.0; p < 0.001). Those receiving red meat were generally more satisfied with this allocation compared to those receiving the PBMAs, even though a leading motivation for participants joining the study was an opportunity to try plant-based eating (35% expressed that their interest in taking part was related to trying plant-based eating). Participants in both intervention groups had increased vegetable intake (p < 0.001), and reported more positive eating experiences (p = 0.020) and satisfaction with eating (p = 0.021) at the end of the 10-week intervention relative to baseline values. Conclusion: Methods to encourage engagement with the trial were successful, as participants demonstrated excellent adherence to the intervention. Observed differences in participants' adherence and experiences between flexitarian and vegetarian groups holds implications for the adoption of healthy, sustainable dietary patterns beyond this study alone.

10.
Food Chem X ; 13: 100218, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35498975

RESUMO

Kokumi tastants are small γ-glutamyl peptides (GGP) that enhance flavour in foods. We sought to generate GGP from the meat crusts of dry-cured lamb, an underutilised protein resource, identify these using mass spectrometry, and validate their functional activity using a kokumi-calcium sensing receptor (CaSR) assay. The water-soluble extract (WSE) of meat crust was hydrolysed by protease A (PA) and treated with glutaminase (GA). Fifteen GGP were identified, with 14 being significantly increased in PA and GA groups compared to WSE, as were along with free amino acid levels. The GA extract activated CaSR with higher potency and efficacy than PA and WSE suggesting the generation of potent kokumi tastants. The in vitro receptor assay might be an expedient tool for screening kokumi tastants prior to conducting human sensory analysis. Collectively, our findings indicate that the meat crust can be a valuable source to generate kokumi tastants via a two-step enzymatic reaction.

11.
Curr Dev Nutr ; 6(5): nzac082, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35669048

RESUMO

Background: Red meat is a nutrient-dense food and a dietary staple. A new generation of plant-based meat analogs (PBMAs) have been designed to mimic the experience of eating meat, but there is limited evidence about their digestive efficacy and nutritional quality. Objectives: We compared the postprandial digestive response of a single meal containing meat commercially raised in New Zealand, including lamb, on-farm pasture-raised beef (Pasture), or grain-finished beef (Grain) with a PBMA (Beyond Burger; Beyond Meat) sold through consumer retail. The primary outcome was the appearance of amino acids in plasma. Secondary outcomes included glucose and insulin, appetite assessment, and anthropometry. Methods: Thirty healthy men (20-34 y) participated in a double-blinded randomized crossover trial. Each consumed 1 of the 4 test meals on 4 occasions separated by a washout period of at least 1 wk, following an overnight fast. The meal was a burrito-style wrap containing meat or PBMAs, vegetables, salsa, and seasonings in a flour tortilla. The amount of Pasture, Grain, Lamb, or BB was 220 g raw (∼160 g cooked). Venous blood samples were collected over 4 h. Appetite and hunger status was scored with visual analog scales. Results: Pre-meal amino acid concentrations in plasma did not differ by group (P > 0.9), although several nonessential amino acids differed strongly according to participant BMI. Postprandial amino acids peaked at 2-3 h in all groups. The BB meal produced significantly lower plasma concentrations of total, essential, branched-chain, and non-proteogenic amino acids than the Lamb, Pasture, or Grain meals, based on AUC. There were no significant differences between meal groups in scores for hunger, fullness, or cravings. Conclusions: Red meat meals exhibited greater bioavailability of amino acids compared with the PBMA (BB). Pasture versus Grain origins of the beef had little influence on participants' responses. This trial was registered at ClinicalTrials.gov as NCT04545398.

12.
Foods ; 10(9)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34574113

RESUMO

The development of new food products can be expedited by understanding the physicochemical attributes that are most relevant to consumers. Although many objective analyses are possible, not all are a suitable proxy to serve as quality markers associated with sensory preferences. In this work, we selected nine candidate laboratory assays to use on six commercial salamis, which were also eaten and informally described by a consumer discussion group familiar with China-sourced meat products. Several objective measures were strongly related to the flavour perceptions: (i) texture: instrumental texture values, fat release at oral temperature and fat saturation ratios, (ii) aroma: volatile compounds (e.g., alcohols and esters) associated with microbial fermentation and spices (terpenes and sulphur compounds) and (iii) taste: kokumi taste receptor responses. The fat released at oral temperature was associated with unsaturated fatty acids (r = 0.73). However, there was less explanatory worth for associations between sensory perceptions and proximate composition, water activity, pH or L*, a*, b* colourimetry.

13.
JMIR Res Protoc ; 10(12): e30909, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34931994

RESUMO

BACKGROUND: The trend of flexitarian eating patterns is on the rise, with young adults among the biggest adopters claiming health and environmental reasons to reduce red meat intake. Nutrient-dense meat and animal products are often the lynchpin of these diets, even when consumed only occasionally and in moderate amounts. Red meat provides forms and concentrations of essential proteins, lipids, and micronutrients that are scarce in exclusively vegetarian regimens. OBJECTIVE: The aim of this study is to consider the effects of moderate consumption of lean red meat as part of an otherwise vegetarian balanced diet and its impact on biomarkers of sustained health and well-being. METHODS: A cohort of healthy, young (20-34 years old, n=80) male and female participants will take part in a 2-arm, parallel randomized controlled trial (RCT) for a duration of 12 weeks, with a 3-month posttrial follow-up. The trial will commence with a 2-week assessment period followed by allocation to the intervention arms. The intervention will include the consumption of red meat or meat alternatives 3 times per week for 10 weeks. Blood samples of the participants will be collected to measure changes in erythrocyte fatty acid distribution, circulating amino acids, neurotransmitters, markers of mineral status, and inflammatory markers. Questionnaires to assess well-being and mental health will be undertaken every 2 weeks. Body composition, physical function, and blood parameters will be assessed at allocation (t0), week 5 into the intervention (t5), and post intervention (t10). RESULTS: The protocol has been developed using the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) checklist and the outcomes will be reported in accordance with the CONSORT (Consolidated Standards of Reporting Trials) guidelines. The trial was approved by the New Zealand Ministry of Health's Health and Disability Ethics Committees (protocol 20/STH/157). The results of this study will be communicated via publication. CONCLUSIONS: To our knowledge, this is the first RCT investigating the overarching health consequences of consuming pasture-fed red meat or no meat as part of a healthy diet. TRIAL REGISTRATION: ClinicalTrials.gov NCT04869163; https://clinicaltrials.gov/ct2/show/NCT04869163. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/30909.

14.
Food Chem ; 346: 128950, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33465570

RESUMO

Blanching is an important process in the preparation of navy beans (Phaseolus vulgaris L.) for canning. We here explore the effect of blanching which can profoundly affect protein composition and introduce protein-primary-level modifications. Amino acid analysis showed significantly decreased protein abundance (58.5%) in blanched beans compared to raw beans. Proteomic analyses revealed a decrease in high molecular weight isoforms of the major storage globulin proteins phaseolin (mean fold-change -3.7) and legumin (mean fold-change -2.5) and concomitant increase in their low molecular weight isoforms (mean fold-change 6.4 and 8.3, respectively). Blanched beans also had decreased abundance of lipoxygenase (mean fold-change -13.1), an enzyme responsible for product spoilage during storage. Increased lysinoalanine (up to 47%) and highly modified protein fragments were found in the processing waters, indicating heat- induced modifications. Correlating these molecular level changes thus provides a basis for evaluating how processing parameters can be modified to increase protein food quality.


Assuntos
Manipulação de Alimentos/métodos , Phaseolus/química , Proteínas de Plantas/química , Temperatura Alta , Proteômica
15.
Nutrition ; 89: 111231, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33930787

RESUMO

OBJECTIVES: Dietary strategies to promote successful aging are divergent. Higher-protein diets are recommended to preserve skeletal muscle mass and physical function. Conversely, increased B-vitamin intake, supporting one-carbon (1C) metabolism, reduces the risk of cognitive decline and cardiovascular disease. On the hypothesis that higher protein intake through animal-based sources will benefit 1C regulation by the supply of B vitamins (folate, riboflavin, and vitamins B6 and B12) and methyl donors (choline) despite higher methionine intake, this study explored the effect of a higher-protein diet on 1C metabolite status in older men compared to current protein recommendations. METHODS: Older men (age, 74 ± 3 y) were randomized to receive a diet for 10 wk containing either the recommended dietary allowance (RDA) of protein (0.8 g/kg body weight/d, n = 14), or double that amount (2RDA, n = 15), with differences in protein accounted for by modifying carbohydrate intake. Intervention diets were matched to each individual's energy requirements based on the Harris-Benedict equation and adjusted fortnightly as required depending on physical activity and satiety. Fasting plasma 1C metabolite concentrations were quantified by liquid chromatography coupled with mass spectrometry at baseline and after 10 wk of intervention. RESULTS: Plasma homocysteine concentrations were reduced from baseline to follow-up with both diets. Changes in metabolite ratios reflective of betaine-dependent homocysteine remethylation were specific to the RDA diet, with an increase in the betaine-to-choline ratio and a decrease in the dimethylglycine-to-betaine ratio. Comparatively, increasing folate intake was positively associated with a change in choline concentration and inversely with the betaine-to-choline ratio for the 2RDA group. CONCLUSIONS: Adding to the known benefits of higher protein intake in older people, this study supports a reduction of homocysteine with increased consumption of animal-based protein, although the health effects of differential response of choline metabolites to a higher-protein diet remain uncertain.


Assuntos
Dieta Rica em Proteínas , Complexo Vitamínico B , Idoso , Betaína , Carbono , Colina , Dieta , Ácido Fólico , Homocisteína , Humanos , Masculino
16.
Nutrients ; 13(10)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34684481

RESUMO

A high protein intake at old age is important for muscle protein synthesis, however, this could also trigger protein oxidation with the potential risk for DNA damage. The aim of this study was to investigate whether an increased protein intake at recommended level or well above would affect DNA damage or change levels of reduced (GSH) and oxidised glutathione (GSSG) in community-dwelling elderly subjects. These analyses were performed in two randomized intervention studies, in Austria and in New Zealand. In both randomized control trials, the mean protein intake was increased with whole foods, in the New Zealand study (n = 29 males, 74.2 ± 3.6 years) to 1.7 g/kg body weight/d (10 weeks intervention; p < 0.001)) in the Austrian study (n = 119 males and females, 72.9 ± 4.8 years) to 1.54 g/kg body weight/d (6 weeks intervention; p < 0.001)). In both studies, single and double strand breaks and as formamidopyrimidine-DNA glycosylase-sensitive sites were investigated in peripheral blood mononuclear cells or whole blood. Further, resistance to H2O2 induced DNA damage, GSH, GSSG and CRP were measured. Increased dietary protein intake did not impact on DNA damage markers and GSH/GSSG levels. A seasonal-based time effect (p < 0.05), which led to a decrease in DNA damage and GSH was observed in the Austrian study. Therefore, increasing the protein intake to more than 20% of the total energy intake in community-dwelling seniors in Austria and New Zealand did not increase measures of DNA damage, change glutathione status or elevate plasma CRP.


Assuntos
Dano ao DNA , Proteínas Alimentares/farmacologia , Redes e Vias Metabólicas , Idoso , Idoso de 80 Anos ou mais , Áustria , Biomarcadores/sangue , Ingestão de Energia , Feminino , Humanos , Lipídeos/sangue , Masculino , Nova Zelândia , Nutrientes/análise
17.
Food Res Int ; 137: 109655, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33233234

RESUMO

Selenium (Se) as a co-factor of antioxidant enzymes is metabolically essential for animals. Its presence in muscle can improve the oxidative stability of meat and is a desirable nutrient for consumers. A novel approach to Se supplementation for meat-producing livestock was demonstrated in a 95-day study of young lambs. DL-selenomethionine (SeMet) was administered by subcutaneous injection at day 0 (3-4 weeks of age) and again at day 54. A Control group (n = 9) received carrier only, whilst Medium and High groups (n = 10) received graded levels of Se. Physicochemical attributes of meat quality and sensory characteristics were measured at 1, 3, 14 and 42 days of ageing (vacuum packaged at -1.5 °C), followed by instrumental colour measurements after 7 days of simulated retail display. There were no significant interactions between SeMet treatment and ageing. Muscle pH, drip and cooking losses, initial display colour and sensory evaluations by trained and consumer panels were unaffected by treatment. Smaller changes in colour during display were observed for the Medium group compared to Control (P < 0.05). The shorter range of ageing times improved meat tenderness however extended ageing decreased colour stability. SeMet markedly increased Se concentrations in muscle, blood, kidney and liver (P < 0.05), resulting in Se enriched meat without appreciable changes in meat quality.


Assuntos
Antioxidantes , Selenometionina , Animais , Suplementos Nutricionais , Carne/análise , Nutrientes , Ovinos
18.
Mol Imaging Biol ; 22(2): 367-376, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31209779

RESUMO

PURPOSE: A great challenge in the diagnosis and treatment of prostate cancer is distinguishing between indolent or local disease and aggressive or metastatic disease. Antibody-based positron emission tomography (immuno-PET) as a cancer-specific imaging modality could improve diagnosis of primary disease, aid the detection of metastases to regional lymph nodes as well as to distant sites (e.g., bone), and monitor response to therapy. PROCEDURE: In search for a more physiologically relevant disease model, a human prostate stem cell antigen knock-in (hPSCA KI) mouse model was generated. The use of a syngeneic prostate cancer cell line transduced to express human PSCA (RM-9-hPSCA) enabled the evaluation of anti-PSCA immuno-PET in immunocompetent mice and in the context of normal tissue expression of PSCA. Two PSCA-specific humanized antibody fragments, A11 minibody and A2 cys-diabody, were radiolabeled with positron emitters iodine-124 and zirconium-89, respectively ([124I]A11 Mb and [89Zr]A2cDb), and used for immuno-PET in wild-type, hPSCA KI and tumor-bearing mice. RESULTS: The hPSCA KI mice express PSCA at low levels in the normal prostate, bladder and stomach, reproducing the expression pattern seen in humans. [124I]A11 Mb immuno-PET detected increased levels of PSCA expression in the stomach, and because I-124 is non-residualizing, very little activity was seen in organs of clearance (liver, kidney, spleen). However, due to the longer half-life of the 80 kDa protein, blood activity (and thus urine activity) at 20 h postinjection remains high. The smaller 50 kDa [89Zr]A2cDb cleared faster, resulting in lower blood and background activity, despite the use of a residualizing radiometal. Importantly, [89Zr]A2cDb immuno-PET showed antigen-specific targeting of PSCA-expressing tumors and minimal nonspecific uptake in PSCA-negative controls. CONCLUSION: Tracer biodistribution was not significantly impacted by normal tissue expression of PSCA. [89Zr]A2cDb immuno-PET yielded high tumor-to-blood ratio at early time points. Rapid renal clearance of the 50 kDa tracer resulted in an unobstructed view of the pelvic region at 20 h postinjection that would allow the detection of cancer in the prostate.


Assuntos
Antígenos de Neoplasias/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/diagnóstico por imagem , Radioisótopos , Células-Tronco/citologia , Zircônio , Animais , Antígenos de Neoplasias/genética , Linhagem Celular Tumoral , Cruzamentos Genéticos , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Humanos , Radioisótopos do Iodo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Metástase Neoplásica , Proteínas de Neoplasias/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Próstata , Neoplasias da Próstata/metabolismo , Distribuição Tecidual
19.
Nutrients ; 12(2)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32023931

RESUMO

Cooking changes the texture and tenderness of red meat, which may influence its digestibility, circulatory amino acids (AA) and gastrointestinal (GI) hormonal responses in consumers. In a randomised crossover intervention, healthy males (n = 12) consumed a beef steak sandwich, in which the beef was cooked by either a pan-fried (PF) or sous-vide (SV) method. Plasma AA were measured by ultrahigh performance liquid chromatography (UPLC), while plasma GI hormones were measured using a flow cytometric multiplex array. Following meat ingestion, the circulatory concentrations of some of the essential AA (all the branched-chain AA: leucine, isoleucine and valine; and threonine), some of the nonessential AA (glycine, alanine, tyrosine and proline) and some of the nonproteogenic AA (taurine, citrulline and ornithine) were increased from fasting levels by 120 or 180 min (p < 0.05). There were no differences in circulating AA concentrations between cooking methods. Likewise, of the measured GI hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) concentrations increased from fasting levels after consumption of the steak sandwich (p < 0.05), with no differences between the cooking methods. In the healthy male adults, protein digestion and circulating GI hormone responses to a beef-steak breakfast were unaltered by the different cooking methods.


Assuntos
Aminoácidos/sangue , Culinária/métodos , Proteínas Alimentares/sangue , Hormônios Gastrointestinais/sangue , Carne Vermelha , Adolescente , Adulto , Estudos Cross-Over , Ingestão de Alimentos , Jejum/sangue , Voluntários Saudáveis , Humanos , Masculino , Período Pós-Prandial , Adulto Jovem
20.
Front Nutr ; 7: 595905, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33521034

RESUMO

Faecal proteomics targeting biomarkers of immunity and inflammation have demonstrated clinical application for the identification of changes in gastrointestinal function. However, there are limited comprehensive analyses of the host faecal proteome and how it may be influenced by dietary factors. To examine this, the Homo sapiens post-diet proteome of older males was analysed at the completion of a 10-week dietary intervention, either meeting the minimum dietary protein recommendations (RDA; n = 9) or twice the recommended dietary allowance (2RDA, n = 10). The host faecal proteome differed markedly between individuals, with only a small subset of proteins present in ≥ 60% of subjects (14 and 44 proteins, RDA and 2RDA, respectively, with only 7 common to both groups). No differences were observed between the diet groups on the profiles of host faecal proteins. Faecal proteins were detected from a wide range of protein classes, with high inter-individual variation and absence of obvious impact in response to diets with markedly different protein intake. This suggests that well-matched whole food diets with two-fold variation in protein intake maintained for 10 weeks have minimal impact on human faecal host proteins.

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