RESUMO
Although the standard method to evaluate skeletal muscle protein synthesis (MPS) is muscle biopsy, the method is invasive and problematic for multisite use. We conducted a small pilot study in volunteers to investigate changes in MPS according to skeletal muscle site using a noninvasive method in which 6 healthy young men were given yogurt (containing 20 g milk protein) or water, and 1 h later, l-[11C]methionine ([11C]Met) was administered intravenously. Dynamic PET/CT imaging of their thighs was performed for 60 min. The influx constant Ki of [11C]Met in skeletal muscle protein was calculated as an index of MPS using a Patlak plot, and found to be 0.6%-28% higher after ingesting yogurt than after water in 5 of the 6 volunteer participants, but it was 34% lower in the remaining participant. Overall, this indicated no significant increase in Ki after ingesting milk protein. However, when the quadriceps and hamstring muscles were analyzed separately, we found a significant difference in Ki. This demonstrates the potential of visualizing MPS by calculating the Ki for each voxel and reconstructing it as an image, which presents unique advantages of [11C]Met PET/CT for evaluating MPS, such as site-specificity and visualization.
Assuntos
Metionina , Proteínas Musculares , Músculo Esquelético , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Masculino , Metionina/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Projetos Piloto , Músculo Esquelético/metabolismo , Músculo Esquelético/diagnóstico por imagem , Adulto , Adulto Jovem , Proteínas Musculares/metabolismo , Proteínas Musculares/biossíntese , Radioisótopos de Carbono , Biossíntese de ProteínasRESUMO
The efficacy of low-carbohydrate, high-fat diets, such as ketogenic diets, for cancer patients is of research interest. We previously demonstrated the efficacy of the ketogenic diet in a case study in which medium-chain triglycerides (MCTs) or MCT-containing formula (ketogenic formula) was used as a supplement to increase blood ketone bodies. However, little is known about the amounts needed to induce ketogenic effects and about the usefulness of monitoring of breath acetone. To investigate the pharmacokinetics of MCTs and their metabolites, blood ketone bodies and breath acetone, 24 healthy subjects received one of four single oral doses of the ketogenic formula (equivalent to 0, 10, 20, and 30 g of MCTs) under fasting conditions. Total blood ketone bodies, ß-hydroxybutyrate, octanoic acid, and decanoic acid were increased in a dose-dependent manner. The ketogenic effect was considered to depend on octanoic and decanoic acids, because a positive correlation was observed between them. A strong positive correlation was also observed between total serum ketone bodies and breath acetone at each time points. Therefore, monitoring breath acetone levels seems a less invasive method to predict blood concentrations of ketone bodies during ketogenic diet therapy. Clinical trial registration:https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000032634, UMIN-CTR UMIN000032634.
RESUMO
In the late 2010s, artificial intelligence (AI) technologies became complementary to the research areas of food science and nutrition. This review aims to summarize these technological advances by systematically describing the following: the use of AI in other fields (eg, engineering, pharmacy, and medicine); the history of AI in relation to food science and nutrition; the AI technologies currently used in the agricultural and food industries; and some of the important applications of AI in areas such as immunity-boosting foods, dietary assessment, gut microbiome profile analysis, and toxicity prediction of food ingredients. These applications are likely to be in great demand in the near future. This review can provide a starting point for brainstorming and for generating new AI applications in food science and nutrition that have yet to be imagined.
Assuntos
Inteligência Artificial , Atenção à Saúde , Humanos , Tecnologia de AlimentosRESUMO
Ketogenic diets, which are carbohydrate-restricted high-fat diets, may have therapeutic effects on various diseases, including cancer. However, ketogenic diets are often not standardized and, therefore, results are difficult to interpret. We previously investigated the usefulness of ketogenic diets in cancer therapy, where ketogenic formulas (KF) were used as supplements to enhance blood ketone bodies; however, the amount of KF was determined empirically with reference to blood ketone bodies levels. Here, to determine a standardized optimal amount of KF, we investigated temporal changes in blood ketone bodies (acetoacetic acid (AcAc), ß-hydroxybutyrate (BHB)) and safety in 20 healthy individuals when KF was taken repeatedly under the conditions of a ketogenic diet (UMIN000034216). The diurnal variation in total ketone bodies, and AcAc and BHB levels significantly increased after lunch and after dinner, on the 4th day of KF administration. There were no significant safety issues related to KF in the context of anthropometric, metabolic, nutritional, urological and gastrointestinal parameters. In addition, ketogenic diets lead to changes in gut microbiota. KF showed a decrease in phylum Firmicutes. Our study provides baseline data of the usefulness of KF in a ketogenic diet.
Assuntos
Dieta Cetogênica , Microbioma Gastrointestinal , Ácido 3-Hidroxibutírico/metabolismo , Humanos , Corpos Cetônicos/metabolismo , Masculino , Triglicerídeos/uso terapêuticoRESUMO
There is ongoing debate as to whether or not α-hydroxyisocaproic acid (HICA) positively regulates skeletal muscle protein synthesis resulting in the gain or maintenance of skeletal muscle. We investigated the effects of HICA on mouse C2C12 myotubes under normal conditions and during cachexia induced by co-exposure to TNFα and IFNγ. The phosphorylation of AMPK or ERK1/2 was significantly altered 30 min after HICA treatment under normal conditions. The basal protein synthesis rates measured by a deuterium-labeling method were significantly lowered by the HICA treatment under normal and cachexic conditions. Conversely, myotube atrophy induced by TNFα/IFNγ co-exposure was significantly improved by the HICA pretreatment, and this improvement was accompanied by the inhibition of iNOS expression and IL-6 production. Moreover, HICA also suppressed the TNFα/IFNγ co-exposure-induced secretion of 3-methylhistidine. These results demonstrated that HICA decreases basal protein synthesis under normal or cachexic conditions; however, HICA might attenuate skeletal muscle atrophy via maintaining a low level of protein degradation under cachexic conditions.
Assuntos
Caquexia/tratamento farmacológico , Caproatos/farmacologia , Interferon gama/toxicidade , Interleucina-6/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfa/toxicidade , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Caquexia/induzido quimicamente , Caquexia/metabolismo , Caquexia/patologia , Linhagem Celular , Regulação para Baixo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Metilistidinas/metabolismo , Camundongos , Fibras Musculares Esqueléticas/enzimologia , Fibras Musculares Esqueléticas/patologia , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Fosforilação , Biossíntese de Proteínas , ProteóliseRESUMO
Evidence suggests that oral intake of medium-chain triglycerides (MCTs), which promote the production of ketone bodies, may improve cognitive functions in elderly people; however, the underlying brain mechanisms remain elusive. We tested the hypothesis that cognitive improvement accompanies physiological changes in the brain and reflects the use of ketone bodies as an extra energy source. To this end, by using functional magnetic resonance imaging, cerebral blood oxygenation level-dependent (BOLD) signals were measured while 20 healthy elderly subjects (14 females and 6 males; mean age: 65.7 ± 3.9 years) were engaged in executive function tasks (N-back and Go-Nogo) after ingesting a single MCT meal (Ketonformula®) or placebo meal in a randomized, double-blind placebo-controlled design (UMIN000031539). Morphological characteristics of the brain were also examined in relation to the effects of an MCT meal. The MCT meal improved N-back task performance, and this was prominent in subjects who had reduced grey matter volume in the dorsolateral prefrontal cortex (DLPFC), a region known to promote executive functions. When the participants were dichotomized into high/low level groups of global cognitive function at baseline, the high group showed improved N-back task performance, while the low group showed improved Go-Nogo task performance. This was accompanied by decreased BOLD signals in the DLPFC, indicative of the consumption of ketone bodies as an extra energy source.
Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Dieta Cetogênica/métodos , Imageamento por Ressonância Magnética , Triglicerídeos/administração & dosagem , Idoso , Encéfalo/diagnóstico por imagem , Método Duplo-Cego , Função Executiva/efeitos dos fármacos , Feminino , Voluntários Saudáveis , Humanos , Corpos Cetônicos/metabolismo , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Projetos Piloto , Córtex Pré-Frontal/diagnóstico por imagem , Análise e Desempenho de TarefasRESUMO
Iron deficiency anemia (IDA) due to malnutrition and/or blood loss is a common condition, especially in women of reproductive age. Intense exercise can induce anemia via an inflammatory response, but whether intense exercise affects the efficacy of iron supplementation to treat IDA is unclear. Here, we show in a mouse model of IDA that acute intense swimming increased IL-6 levels in the blood, but did not affect the maximum elevation of plasma iron following oral administration of 0.5 mg/kg Bw iron. However, compared with the control group without intense exercise, acute intense swimming was associated with a significant decrease in plasma iron 2 and 4 h after iron loading that could be attributed to rapid iron absorption in peripheral tissues. In the chronic experiment, IDA mice administered 0.36, 1.06, or 3.2 mg/kg Bw iron per day that were subjected to 11 intense swimming sessions over 3 weeks showed significantly decreased recovery levels for hemoglobin and red blood cell count during the early phase of the experimental period. At the end of the experimental period, significant, dose-dependent effects of iron, but not the main effect of intense exercise, were seen for recovery of hemoglobin and red blood cell counts, consistent with the acute exercise study. These results suggested that intense exercise in the presence of IDA does not inhibit iron absorption from the gastrointestinal tract and that iron supplementation can enhance the recovery process even after intense exercise.
Assuntos
Anemia Ferropriva , Anemia , Anemia Ferropriva/tratamento farmacológico , Animais , Suplementos Nutricionais , Hemoglobinas/análise , Ferro , CamundongosRESUMO
NEW FINDINGS: What is the central question of this study? Is stretch-shortening contraction effective to attenuate skeletal muscle atrophy and hepatic dysfunction in a rat model of peptidoglycan-polysaccharide (PG-PS)-induced inflammation (PG-PS rat)? What are the main findings and their importance? Stretch-shortening contraction attenuates skeletal muscle atrophy in the trained leg and increases circulating interleukin-10 in PG-PS rats. Stretch-shortening contraction also ameliorates liver dysfunction in PG-PS rats, possibly via increased blood interleukin-10. These findings are important because they suggest that stretch-shortening contraction is effective to maintain liver function in addition to exercised skeletal muscle mass. ABSTRACT: Stretch-shortening contraction (SSC) is an effective modality to improve skeletal muscle mass. However, the beneficial effects of SSC in the presence of chronic inflammation remain unclear. Here, we imposed five SSC sessions unilaterally on the triceps surae in young female Lewis rats. Rats were injected with vehicle or peptidoglycan-polysaccharide (PG-PS) to induce long-lasting inflammation. The PG-PS reduced gastrocnemius muscle mass in both legs, but that of the SSC-trained leg was significantly greater than that of the contralateral leg. Circulating pro-inflammatory cytokines, such as IL-1ß, were significantly increased by PG-PS injection, even if carrying out SSC. The circulating anti-inflammatory cytokine IL-10 increased with SSC in both healthy and inflammatory conditions. Stretch-shortening contraction also prevented increases in serum aspartate aminotransferase activity and plasma free phenylalanine concentration induced by PG-PS, in comparison to the control resistance exercise consisting of isometric contractions. Moreover, aspartate aminotransferase and phenylalanine concentrations demonstrated a significant and negative correlation with IL-10/IL-1ß values (r = -0.61, P = 0.017, and r = -0.66, P = 0.008, respectively). These results suggest that SSC training is effective to reduce both muscle atrophy and the hepatic dysfunction induced by PG-PS, mediated, at least in part, through an increase in circulating IL-10.
Assuntos
Inflamação/fisiopatologia , Contração Isométrica , Hepatopatias/fisiopatologia , Músculo Esquelético/fisiologia , Atrofia Muscular/prevenção & controle , Animais , Citocinas/sangue , Feminino , Inflamação/induzido quimicamente , Interleucina-10/sangue , Interleucina-6/sangue , Condicionamento Físico Animal , Ratos , Ratos Endogâmicos LewRESUMO
Chronic inflammation (CI) can contribute to muscle atrophy and sarcopenia. Resistance exercise (RE) promotes increased and/or maintenance of skeletal muscle mass, but the effects of RE in the presence of CI are unclear. In this study, we developed a novel animal model of CI-induced muscle atrophy and examined the effect of acute or chronic RE by electrical stimulation. CI was induced in young female Lewis rats by injection with peptidoglycan-polysaccharide (PG-PS). Extracellular signal-regulated kinase (ERK), p70S6 kinase (p70S6K), 4E binding protein 1 (4E-BP1), Akt, and Forkhead box O1 (FOXO1) phosphorylation levels increased in gastrocnemius (Gas) muscle from normal rats subjected to acute RE. After acute RE in CI rats, increased levels of phosphorylated ERK, p70S6K, and 4E-BP1, but not Akt or FOXO1, were observed. Chronic RE significantly increased the Gas weight in the exercised limb relative to the nontrained opposing limb in CI rats. Dietary supplementation with anti-inflammatory agents, eicosapentaenoic/docosahexaenoic acid and α-lactalbumin attenuated CI-induced muscle atrophy in the untrained Gas and could promote RE-induced inhibition of atrophy in the trained Gas. In the trained leg, significant negative correlations (r ≤ -0.80) were seen between Gas weights and CI indices, including proinflammatory cytokines and white blood cell count. These results indicated that the anabolic effects of RE are effective for preventing CI-induced muscle atrophy but are partially attenuated by inflammatory molecules. The findings also suggested that anti-inflammatory treatment together with RE is an effective intervention for muscle atrophy induced by CI. Taken together, we conclude that systemic inflammation levels are associated with skeletal muscle protein metabolism and plasticity.NEW & NOTEWORTHY This study developed a novel chronic inflammation (CI) model rat demonstrating that resistance exercise (RE) induced activation of protein synthesis signaling pathways and mitigated skeletal muscle atrophy. These anabolic effects were partially abrogated likely through attenuation of Akt/Forkhead box O1 axis activity. The degree of skeletal muscle atrophy was related to inflammatory responses. Dietary supplementation with anti-inflammatory agents could enhance the anabolic effect of RE. Our findings provide insight for development of countermeasures for CI-related muscle atrophy, especially secondary sarcopenia.
Assuntos
Anti-Inflamatórios/farmacologia , Alimento Funcional/análise , Inflamação/complicações , Músculo Esquelético/patologia , Atrofia Muscular/prevenção & controle , Treinamento Resistido , Animais , Doença Crônica , Feminino , Proteínas Musculares/metabolismo , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Fosforilação , Ratos , Ratos Endogâmicos LewRESUMO
Cancer chemotherapy is frequently accompanied by adverse effects, such as diarrhoea and leukopenia, which lead to malnutrition and a decrease in the patients' quality of life. We previously demonstrated that an immune-modulating formula (IMF)-an enteral formula enriched with immunonutrients, whey-hydrolysed peptides, and fermented milk-had anti-inflammatory effects and protective effects on intestinal disorders in some experimental models. Here, we investigated whether nutritional treatment with the IMF could prevent 5-fluorouracil (5-FU)-induced adverse effects in rats. Rats were randomised into CTR and IMF groups, which received a control formula or the IMD supplemented formula ad libitum. Two weeks after starting the formula, rats were intraperitoneally injected with 5-FU (300 mg/kg) on day 0. The treatment with 5-FU decreased their body weights, food intake, and leukocyte counts, and worsened the diarrhoea score. However, the body weights, food intake, and leukocyte counts were significantly higher in the IMF rats than in the CTR rats on day 1. The IMF also delayed the incidence of diarrhoea and significantly preserved the villus heights in the jejunum on day 2. In conclusion, nutritional treatment with the IMF alleviated the adverse effects induced by 5-FU injection in rats.
Assuntos
Fluoruracila/efeitos adversos , Fatores Imunológicos/administração & dosagem , Enteropatias/dietoterapia , Animais , Peso Corporal/efeitos dos fármacos , Produtos Fermentados do Leite , Suplementos Nutricionais , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Nutrição Enteral , Fatores Imunológicos/farmacologia , Enteropatias/induzido quimicamente , Masculino , Ratos , Ratos WistarRESUMO
Clinical and animal studies suggested that a medium-chain triglyceride (MCT)-based ketogenic diet provides an alternative energy substrate to the brain and has neuroprotective effects, but the clinical evidence is still scarce. Here we examined the effect of an MCT-based ketogenic formula on cognitive function in patients with Alzheimer's disease (AD). The subjects were 20 Japanese patients with mild-to-moderate AD (11 males, nine females, mean age 73.4 ± 6.0 years) who, on separate days, underwent neurocognitive tests 120 min after consuming 50 g of a ketogenic formula (Ketonformula®) containing 20 g of MCTs or an isocaloric placebo formula without MCTs. The patients then took 50 g of the ketogenic formula daily for up to 12 weeks, and underwent neurocognitive tests monthly. In the first trial, although the patients' plasma levels of ketone bodies were successfully increased 120 min after the single intake of the ketogenic formula, there was no significant difference in any cognitive test results between the administrations of the ketogenic and placebo formulae. In the subsequent chronic intake trial of the ketogenic formula, 16 of the 20 patients completed the 12-week regimen. At 8 weeks after the trial's start, the patients showed significant improvement in their immediate and delayed logical memory tests compared to their baseline scores, and at 12 weeks they showed significant improvements in the digit-symbol coding test and immediate logical memory test compared to the baseline. The chronic consumption of the ketogenic formula was therefore suggested to have positive effects on verbal memory and processing speed in patients with AD.
Assuntos
Doença de Alzheimer/dietoterapia , Doença de Alzheimer/psicologia , Cognição/efeitos dos fármacos , Dieta Cetogênica , Triglicerídeos/química , Triglicerídeos/uso terapêutico , Idoso , Doença de Alzheimer/sangue , Método Duplo-Cego , Feminino , Humanos , Corpos Cetônicos/sangue , Masculino , Testes NeuropsicológicosRESUMO
Low-carbohydrate, high-fat diets (ketogenic diets) might prevent tumor progression and could be used as supportive therapy; however, few studies have addressed the effect of such diets on colorectal cancer. An infant formula with a ketogenic composition (ketogenic formula; KF) is used to treat patients with refractory epilepsy. We investigated the effect of KF on cancer and cancer cachexia in colon tumor-bearing mice. Mice were randomized into normal (NR), tumor-bearing (TB), and ketogenic formula (KF) groups. Colon 26 cells were inoculated subcutaneously into TB and KF mice. The NR and TB groups received a standard diet, and the KF mice received KF ad libitum. KF mice preserved their body, muscle, and carcass weights. Tumor weight and plasma IL-6 levels were significantly lower in KF mice than in TB mice. In the KF group, energy intake was significantly higher than that in the other two groups. Blood ketone body concentrations in KF mice were significantly elevated, and there was a significant negative correlation between blood ketone body concentration and tumor weight. Therefore, KF may suppress the progression of cancer and the accompanying systemic inflammation without adverse effects on weight gain, or muscle mass, which might help to prevent cancer cachexia.
Assuntos
Adenocarcinoma/dietoterapia , Caquexia/prevenção & controle , Neoplasias Colorretais/dietoterapia , Dieta Cetogênica , Síndrome de Resposta Inflamatória Sistêmica/prevenção & controle , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adenocarcinoma/fisiopatologia , Adiposidade , Animais , Caquexia/etiologia , Caquexia/imunologia , Linhagem Celular Tumoral , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Neoplasias Colorretais/fisiopatologia , Dieta Cetogênica/efeitos adversos , Ingestão de Energia , Interleucina-6/sangue , Corpos Cetônicos/sangue , Masculino , Camundongos , Músculo Esquelético/patologia , Transplante de Neoplasias , Tamanho do Órgão , Distribuição Aleatória , Reprodutibilidade dos Testes , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Carga Tumoral , Redução de PesoRESUMO
RATIONALE: Glucose is the principal energy substrate for the brain, although ketone bodies are an effective alternative. Evidence suggests that elevation of plasma ketone body levels through oral intake of medium chain triglycerides (MCTs) may improve cognitive function. OBJECTIVES: We tried to examine the possible effects of a ketogenic meal serving on cognition in elderly non-demented subjects. METHODS: Subjects were 19 non-demented elderly adults over 60 years old (13 females; mean age: 66.1 ± 2.9 years) who underwent neurocognitive tests 90 and 180 min after oral intake of a ketogenic meal (Ketonformula®) containing 20 g of MCTs and an isocaloric placebo meal without MCTs on separate days. RESULTS: Elevation of plasma ketone concentration after intake of a single ketogenic meal containing 20 g of MCTs was confirmed (all p < 0.001). As for cognition, improvements were observed in the digit span test, Trail-Making Test B, and the global score (Z = -2.4, p = 0.017) following the ketogenic meal and the change in the executive functioning score was positively correlated with that of the plasma ß-hydroxybutyrate level. The cognition-enhancing effect was observed predominantly for individuals who had a relatively low global score at baseline (Z = -2.8, p = 0.005), compared to individuals with a high global score (Z = -0.7, p = 0.51). CONCLUSIONS: Plasma levels of ketone bodies were successfully increased after intake of the ketogenic meal. The ketogenic meal was suggested to have positive effects on working memory, visual attention, and task switching in non-demented elderly.
Assuntos
Ácido 3-Hidroxibutírico/sangue , Atenção , Cognição , Dieta Cetogênica , Corpos Cetônicos/sangue , Memória de Curto Prazo , Idoso , Encéfalo/metabolismo , Feminino , Glucose/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , TriglicerídeosRESUMO
A fluid-retention effect is required for beverages that are designed to prevent dehydration. That is, fluid absorbed from the intestines should not be excreted quickly; long-term retention is desirable. Here, we focused on the effect of milk protein on fluid retention, and propose a new effective oral rehydration method that can be used daily for preventing dehydration. We first evaluated the effects of different concentrations of milk protein on fluid retention by measuring the urinary volumes of rats fed fluid containing milk protein at concentrations of 1, 5, and 10%. We next compared the fluid-retention effect of milk protein-enriched drink (MPD) with those of distilled water (DW) and a sports drink (SD) by the same method. Third, to investigate the mechanism of fluid retention, we measured plasma insulin changes in rats after ingesting these three drinks. We found that the addition of milk protein at 5 or 10% reduced urinary volume in a dose-dependent manner. Ingestion of the MPD containing 4.6% milk protein resulted in lower urinary volumes than DW and SD. MPD also showed a higher water reabsorption rate in the kidneys and higher concentrations of plasma insulin than DW and SD. These results suggest that increasing milk protein concentration in a beverage enhances fluid retention, which may allow the possibility to develop rehydration beverages that are more effective than SDs. In addition, insulin-modifying renal water reabsorption may contribute to the fluid-retention effect of MPD.
Assuntos
Água Corporal/metabolismo , Desidratação/metabolismo , Hidratação/métodos , Proteínas do Leite/administração & dosagem , Leite/química , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Água/metabolismo , Animais , Bebidas , Desidratação/dietoterapia , Desidratação/etiologia , Desidratação/prevenção & controle , Carboidratos da Dieta/farmacologia , Relação Dose-Resposta a Droga , Ingestão de Líquidos , Insulina/sangue , Rim/efeitos dos fármacos , Masculino , Proteínas do Leite/farmacologia , Proteínas do Leite/uso terapêutico , Ratos Sprague-Dawley , Cloreto de Sódio na Dieta/farmacologia , Sudorese , MicçãoRESUMO
This study aimed to investigate the effects of a combination of a dairy product fermented by lactobacilli (DFL) and galactooligosaccharides (GOS) on mineral balances in growing rats with hypochlorhydria induced by a proton pump inhibitor (PPI). Three-week-old male rats were assigned to receive one of six diets: a control diet, control diets containing 1.6 or 5.0 % GOS, a DFL diet and DFL diets containing 1.6 or 5.0 % GOS for 9 days. From day 5 of the feeding period, half of the rats fed with control diets were subcutaneously administered with saline, whereas the remaining rats were administered with PPI for 5 days. Calcium (Ca), phosphorus (P), magnesium (Mg), iron (Fe) and zinc (Zn) balances were determined from days 6 to 9. PPI administration significantly decreased the apparent absorption of Ca and Fe and increased urinary P excretion, resulting in decreased Ca, Fe and P retention. GOS dose-dependently increased the apparent absorption of Ca, Mg and Fe and urinary Mg excretion and decreased urinary P excretion. DFL significantly increased the apparent absorption of Ca and Mg and urinary Mg excretion. The combination of DFL and GOS additively affected these parameters, resulting in increased Ca, P and Fe retention, and it further increased the apparent absorption and retention of Zn at 5.0 % GOS. In conclusion, the combination of DFL and GOS improves Ca, P and Fe retention in an additive manner and increases the Zn retention in growing rats with hypochlorhydria induced by PPI.
Assuntos
Acloridria/tratamento farmacológico , Laticínios , Fermentação , Lactobacillus/metabolismo , Oligossacarídeos/metabolismo , Inibidores da Bomba de Prótons/efeitos adversos , Acloridria/induzido quimicamente , Animais , Densidade Óssea , Masculino , Inibidores da Bomba de Prótons/uso terapêutico , Ratos , Ratos Sprague-Dawley , Tomografia Computadorizada por Raios XRESUMO
The purpose of the present study is to investigate the effects of hypochlorhydria induced by proton pump inhibitor (PPI) administration and intake of a dairy product fermented by lactobacilli (DFL) on bone metabolism in growing rats. Male rats, aged 3 weeks, were divided into two groups: a control group fed a casein-based diet and a group fed a DFL-based diet. Each group was fed its respective experimental diets for 9 d. At day 5 of the feeding period, each group was divided into two subgroups: one that received a saline injection and one that received a PPI injection. Rats were subcutaneously administered saline or PPI for 5 d. Faecal Ca excretion was determined from day 6 to day 9. At the end of the experiment, plasma and femurs were collected. Administration of PPI significantly decreased bone mineral density (shown by X-ray computerised tomography) and bone strength (shown by a three-point bending test) in the control group. Plasma osteocalcin, type I collagen C-telopeptides, 1,25-dihydroxyvitamin D and parathyroid hormone concentrations were elevated by PPI administration in the control group. Faecal Ca excretion and urinary P excretion in the control group were remarkably increased by PPI administration. On the other hand, these adverse effects of PPI were not observed in the DFL group. These results suggest that hypochlorhydria-induced bone loss may result from high bone turnover induced by secondary hyperparathyroidism due to Ca malabsorption and that DFL intake cancels these adverse effects probably via improving Ca malabsorption in growing rats.
Assuntos
Acloridria/metabolismo , Osso e Ossos/metabolismo , Laticínios , Fermentação , Lactobacillus/metabolismo , Inibidores da Bomba de Prótons/farmacologia , Animais , Peso Corporal , Densidade Óssea , Osso e Ossos/efeitos dos fármacos , Cálcio/metabolismo , Suco Gástrico/metabolismo , Concentração de Íons de Hidrogênio , Masculino , Fósforo/metabolismo , Ratos , Ratos Sprague-Dawley , Tomografia Computadorizada por Raios XAssuntos
Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Reestenose Coronária/diagnóstico por imagem , Vasos Coronários/patologia , Anastomose de Artéria Torácica Interna-Coronária/reabilitação , Recuperação de Função Fisiológica , Angioplastia Coronária com Balão/efeitos adversos , Doença das Coronárias/terapia , Reestenose Coronária/etiologia , Reestenose Coronária/fisiopatologia , Reestenose Coronária/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Stents/efeitos adversos , Tempo , Resultado do TratamentoRESUMO
Human lactoferrin (hLf) has been shown to interact with cells from the Caco-2 human small intestinal cell line. There currently is little information about the molecular details of its interaction. As a first step toward detailed characterization of this interaction, we used a series of Lf chimeras to analyze which part of Lf is responsible for the interaction with Caco-2 cells. Recombinant chimeric proteins consisting of segments of hLf and bovine transferrin (bTf) were produced in a baculovirus-insect cell system and purified by a combination of cation exchange chromatography and immobilized bTf antibody affinity chromatography. Each chimera was labeled with a green fluorescent dye to monitor its interaction with Caco-2 cells. Similarly, the intestinal Lf receptor (LfR), also known as intelectin, was probed with an anti-LfR antibody that was detected with a secondary antibody conjugated with a red-color fluorescent dye. The results demonstrated that chimeric proteins containing the N-lobe or the N1.1 subdomain of Lf bound as well as intact Lf to Caco-2 cells. Confocal microscopy analysis revealed that these proteins, along with the LfR, were internalized and targeted to the nucleus. These results indicate that the N1.1 subdomain of hLf is sufficient for binding, internalization, and targeting to the nucleus of Caco-2 cells.
Assuntos
Núcleo Celular/metabolismo , Lactoferrina/metabolismo , Sequência de Aminoácidos , Células CACO-2 , Eletroforese em Gel de Poliacrilamida , Corantes Fluorescentes/metabolismo , Humanos , Lactoferrina/química , Microscopia Confocal , Microscopia de Fluorescência , Dados de Sequência Molecular , Proteínas Recombinantes de Fusão/metabolismoRESUMO
We studied the cellular internalization of lactoferrin (Lf) in an intestinal epithelial cell line, Caco-2, to investigate the mechanism of biological actions of ingested Lf. RT-PCR and Western blotting analyses revealed that differentiated Caco-2 cells express LfR mRNA and its protein with a 34 kD molecular weight under reducing conditions. Biotin-labeled Lf showed specific binding to the cellular membrane of differentiated Caco-2 cells with a dissociation constant (Kd) of 0.16 microM. The cellular internalization of Lf was studied in differentiated Caco-2 cells grown as monolayers on Transwell inserts, and compared to that of human transferrin (Tf). After labeling with fluorescent dye, either Lf or Tf was added to Caco-2 cells from the apical side or the basolateral one. Laser scanning confocal microscopy showed that labeled Lf was internalized only from the apical side and localized to the nuclei. On the other hand, labeled Tf was internalized from the basolateral side, not from the apical side, and localized in the cytoplasm. The internalization of labeled Lf was inhibited by excess of unlabeled Lf, but not of Tf. The internalization of labeled Lf, but not of labeled Tf, was also suppressed by heparin. This indicates that a heparin-binding site in the N-terminal region of Lf could be important for the internalization of Lf. These findings suggest that ingested Lf might be internalized by the intestinal epithelium in a manner different from Tf and might function in the nucleus.
Assuntos
Endocitose/fisiologia , Células Epiteliais/metabolismo , Mucosa Intestinal/citologia , Lactoferrina/metabolismo , Animais , Células CACO-2 , Membrana Celular/metabolismo , Células Epiteliais/citologia , Heparina/metabolismo , Humanos , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Transferrina/metabolismoRESUMO
Midkine (MK) is a heparin-binding growth factor, which promotes growth, migration, and survival of various cells, and MK expression is increased in many human carcinomas. We determined the urinary MK level by enzyme-linked immunoassay. Taking 311pg/mg creatinine as a cut-off level, 70% of patients with various carcinomas (n=142) gave positive values, while only 5.5% of healthy volunteers (n=330) did. In case of gastric carcinoma, 17 out of 21 patients with stage 1 tumor were positive. Urinary MK levels are expected to become a convenient marker as an aid in detection of tumors.