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1.
J Med Food ; 23(5): 485-490, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31634026

RESUMO

The impact of oral supplementation with an effervescent glutamine formulation on the beneficial effects of antiretroviral therapies was evaluated in people living with HIV/AIDS. For this purpose, 12 HIV/AIDS carrier patients with CD4+ T cell counts <500, and who had received the same antiretroviral therapy for at least 1 year before starting this investigation were selected. The patients were required to dissolve the effervescent glutamine formulation (supplied in sachets) in water immediately before oral ingestion (12.4 g), once a day, after lunch or after dinner during 30 days. CD4+ T cell counts, complete blood cell counts, serum cytokines, and amino acids levels were quantified; biochemical and toxicological measurements were performed. The numbers of CD4+ T cells were increased (P < .05), and the serum C-reactive protein levels decreased (P < .01) after the administration of effervescent glutamine formulation. Serum levels of interferon-gamma inducible protein-10, RANTES, and macrophage inflammatory protein-1ß were decreased after the treatment with effervescent glutamine formulation. No changes were observed in the serum levels of amino acids, hematological, toxicological, and biochemical parameters. In conclusion, the treatment during 30 days with effervescent glutamine formulation was well tolerated, promoted reduction of inflammation, and improved the beneficial effects of antiretroviral therapies in HIV/AIDS carrier patients.

2.
J Cell Biochem ; 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30719751

RESUMO

Gluconeogenesis (GN) is increased in patients with cancer cachexia, but is reduced in liver perfusion of Walker-256 tumor-bearing cachectic rats (TB rats). The causes of these differences are unknown. We investigated the influence of circulating concentrations of lactate (NADH generator) and NADH on GN in perfused livers of TB rats. Lactate, at concentrations similar to those found on days 5 (3.0 mM), 8 (5.5 mM), and 12 (8.0 mM) of the tumor, prevented the reduction of GN from 2.0 mM lactate (lactatemia of healthy rat) in TB rats. NADH, 50 or 75 µM, but not 25 µM, increased GN from 2.0 mM lactate in TB rats to higher values than healthy rats. High concentrations of pyruvate (no NADH generator, 5.0 and 8.0 mM) did not prevent the reduction of GN from 2.0 mM pyruvate in TB rats. However, 50 or 75 µM NADH, but not 25 µM, increased GN from 2.0 mM pyruvate in TB rats to similar or higher values than healthy rats. High concentration of glutamine (NADH generator, 2.5 mM) or 50 µM NADH prevented the reduction of GN from 1 mM glutamine in TB rats. Intraperitoneal administration of pyruvate (1.0 mg/kg) or glutamine (0.5 mg/kg) similarly increased the glycemia of healthy and TB rats. In conclusion, high lactate concentration, similar to hyperlactatemia, prevented the reduction of GN in perfused livers of TB rats, an effect probably caused by the increased redox potential (NADH/NAD+ ). Thus, the decreased GN in livers from TB rats is due, at least in part, to the absence of simulation of in vivo hyperlactatemia in liver perfusion studies.

3.
Pharm Dev Technol ; 24(1): 12-23, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29172854

RESUMO

Catabolic conditions like acquired immunodeficiency syndrome, cancer, and burn can cause immunosuppression. Amino acids such as alanine and glutamine are essential for the activity of the immune system. Propolis is immunostimulant and the waste of propolis extraction has been reused with technological and therapeutic purposes. Therefore, this study describes the association of propolis byproduct extract (BPE) with pectin to prepare spray-dried microparticles containing the dipeptide l-alanyl-l-glutamine as stimulant systems of neutrophils. The use of a factorial design allowed selecting the best formulation, which was characterized by morphology, size, and entrapment efficiency analyses. In addition, the systems were characterized by thermal and X-ray diffraction analysis, Fourier-transform infrared spectroscopy, in vitro drug release, and in vitro cytotoxicity and stimulation test of neutrophils. Small well-structured microparticles with good entrapment efficiency values were achieved. Thermal stability of formulation was observed, and it was proved that pectin, BPE and l-alanyl-l-glutamine were dispersed throughout the matrix. The drug was released from the microparticles during 24 h governed by swelling and diffusion. The drug-loaded formulations showed a significant stimulating effect on neutrophils. These structures could increase the activity of immune cells, and other in vitro and in vivo studies should be performed in the future.


Assuntos
Dipeptídeos/administração & dosagem , Neutrófilos/efeitos dos fármacos , Pectinas/química , Própole/química , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/toxicidade , Química Farmacêutica/métodos , Dipeptídeos/farmacologia , Dipeptídeos/toxicidade , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Técnicas In Vitro , Microesferas , Neutrófilos/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Fatores de Tempo , Difração de Raios X
4.
Biomed Res Int ; 2018: 2525670, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29850491

RESUMO

The aim of the present study was to investigate the effect of a short period of supplementation with glutamine dipeptide (GDP) on the acute responses to resistance training on the executive functions of people with HIV/AIDS. The sample consisted of 10 HIV+ women (45.00 ± 12.77 years old; 65.71 ± 12.04 kg; 1.54 ± 0.05 m) who were submitted to a randomized double-blind crossover procedure according to two experimental conditions: orally supplemented with 20 g/day of GDP or with maltodextrin for seven days. On the seventh day of supplementation all participants did cognitive function tests before and immediately after a resistance training session. Seven days of washout were adopted between conditions. Stroop and N-back tests were used to evaluate the executive functions. The training reduced the response time of each card in isolation and the latency time among them. GDP supplementation increased the magnitude of this effect, thus, reducing the latency time from the first to the last card in the Stroop test by almost 50% (P < 0.01). Considering the N-back test, there were no significant differences. It is suggested that GDP supplementation may increase the magnitude of the effect of an acute resistance training session in cognitive functions, particularly in the inhibitory control of people with HIV/AIDS. This trial is registered with NCT03236532.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/fisiopatologia , Cognição , Suplementos Nutricionais , Dipeptídeos/uso terapêutico , Glutamina/uso terapêutico , Treinamento de Resistência , Cognição/efeitos dos fármacos , Estudos Cross-Over , Dipeptídeos/farmacologia , Método Duplo-Cego , Feminino , Glutamina/farmacologia , Humanos , Pessoa de Meia-Idade , Placebos , Teste de Stroop
5.
Braz. J. Pharm. Sci. (Online) ; 54(2): e17617, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-951924

RESUMO

ABSTRACT We investigated whether oral lactate could prevent seizures and deaths in mice with severe hypoglycemia induced by a high dose of insulin. For this purpose, mice were fasted for 15 h and then given an intraperitoneal injection of regular insulin (5.0 U/kg or 10.0 U/kg). Immediately after insulin injection, the mice received an oral dose of saline (control), glucose (5.5 mmol/kg), or lactate (18.0 mmol/kg). Glucose and lactate levels were measured in the blood and brain before and after the seizures began. Glucose and lactate delayed (p < 0.05) the onset of seizures associated with severe insulin-induced hypoglycemia. Elevated (p < 0.05) brain levels of lactate were associated with an absence of seizures in mice that received glucose or lactate, suggesting that lactate could prevent convulsions associated with severe insulin-induced hypoglycemia. However, the same oral dose of lactate that delayed the onset of convulsions also increased the mortality rate. In contrast, diazepam (3.0 mg/kg) prevented seizures and markedly decreased the frequency of death during severe insulin-induced hypoglycemia. The results demonstrated that in contrast to oral glucose, oral lactate intensifies insulin toxicity.


Assuntos
Animais , Masculino , Feminino , Ratos , Hipoglicemia/induzido quimicamente , Insulina/administração & dosagem , Anticonvulsivantes/efeitos adversos , Ácido Láctico/efeitos adversos , Diazepam
6.
Eur J Pharmacol ; 806: 67-74, 2017 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-28390870

RESUMO

Cachexia is the main cause of mortality in advanced cancer patients. We investigated the effects of insulin (INS) and glutamine dipeptide (GDP), isolated or associated, on cachexia and metabolic changes induced by Walker 256 tumor in rats. INS (NPH, 40 UI/kg, sc) or GDP (1.5g/kg, oral gavage) was once-daily administered during 11 days after tumor cell inoculation. GDP, INS or INS+GDP treatments did not influence the tumor growth. However, INS and INS+GDP prevented retroperitoneal fat wasting and body weight loss of tumor-bearing rats. In consistency, INS and INS+GDP prevented the increased expression of triacylglycerol lipase (ATGL) and hormone sensitive lipase (HSL), without changing the expression of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in the retroperitoneal adipose tissue of tumor-bearing rats. INS and INS+GDP also prevented anorexia and hyperlactatemia of tumor-bearing rats. However, INS and INS+GDP accentuated the loss of muscle mass (gastrocnemius, soleus and long digital extensor) without affecting the myostatin expression in the gastrocnemius muscle and blood corticosterone. GDP treatment did not promote beneficial effects. It can be concluded that treatment with INS (INS or INS+GDP), not with GDP, prevented fat wasting and weight loss in tumor-bearing rats without reducing tumor growth. These effects might be attributed to the reduction of lipases expression (ATGL and LHS) and increased food intake. The results show the physiological function of INS in the suppression of lipolysis induced by cachexia mediators in tumor-bearing rats.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Caquexia/prevenção & controle , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Insulina/farmacologia , Lipase/metabolismo , Neoplasias Mamárias Animais/complicações , Perda de Peso/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Caquexia/complicações , Linhagem Celular Tumoral , Interleucina-6/metabolismo , Masculino , Neoplasias Mamárias Animais/enzimologia , Neoplasias Mamárias Animais/patologia , Neoplasias Mamárias Animais/fisiopatologia , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
7.
Cell Stress Chaperones ; 22(2): 271-291, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28251488

RESUMO

Exercise stimulates immune responses, but the appropriate "doses" for such achievements are unsettled. Conversely, in metabolic tissues, exercise improves the heat shock (HS) response, a universal cytoprotective response to proteostasis challenges that are centred on the expression of the 70-kDa family of intracellular heat shock proteins (iHSP70), which are anti-inflammatory. Concurrently, exercise triggers the export of HSP70 towards the extracellular milieu (eHSP70), where they work as pro-inflammatory cytokines. As the HS response is severely compromised in chronic degenerative diseases of inflammatory nature, we wondered whether acute exercise bouts of different intensities could alter the HS response of lymphocytes from secondary lymphoid organs and whether this would be related to immunoinflammatory responses. Adult male Wistar rats swam for 20 min at low, moderate, high or strenuous intensities as per an overload in tail base. Controls remained at rest under the same conditions. Afterwards, mesenteric lymph node lymphocytes were assessed for the potency of the HS response (42 °C for 2 h), NF-κB binding activity, mitogen-stimulated proliferation and cytokine production. Exercise stimulated cell proliferation in an "inverted-U" fashion peaking at moderate load, which was paralleled by suppression of NF-κB activation and nuclear location, and followed by enhanced HS response in relation to non-exercised animals. Comparative levels of eHSP70 to iHSP70 (H-index) matched IL-2/IL-10 ratios. We conclude that exercise, in a workload-dependent way, stimulates immunoinflammatory performance of lymphocytes of tissues far from the circulation and this is associated with H-index of stress response, which is useful to assess training status and immunosurveillance balance.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Resposta ao Choque Térmico/fisiologia , Interleucina-10/metabolismo , Interleucina-2/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Linfócitos/citologia , Linfócitos/metabolismo , Masculino , Microscopia Eletrônica , Microscopia de Fluorescência , NF-kappa B/metabolismo , Condicionamento Físico Animal , Ratos , Ratos Wistar , Temperatura
8.
Tumour Biol ; 39(3): 1010428317695960, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28345452

RESUMO

We evaluated the effects of supplementation with oral l-glutamine in Walker-256 tumor-bearing rats. A total of 32 male Wistar rats aged 54 days were randomly divided into four groups: rats without Walker-256 tumor, that is, control rats (C group); control rats supplemented with l-glutamine (CG group); Walker-256 tumor rats without l-glutamine supplementation (WT group); and WT rats supplemented with l-glutamine (WTG group). l-Glutamine was incorporated into standard food at a proportion of 2 g/100 g (2%). After 10 days of the experimental period, the jejunum and duodenum were removed and processed. Protein expression levels of key enzymes of gluconeogenesis, that is, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, were analyzed by western blot and immunohistochemical techniques. In addition, plasma corticosterone, glucose, insulin, and urea levels were evaluated. The WTG group showed significantly increased plasma glucose and insulin levels ( p < 0.05); however, plasma corticosterone and urea remained unchanged. Moreover, the WTG group showed increased immunoreactive staining for jejunal phosphoenolpyruvate carboxykinase and increased expression of duodenal glucose-6-phosphatase. Furthermore, the WTG group presented with less intense cancer cachexia and slower tumor growth. These results could be attributed, at least partly, to increased intestinal gluconeogenesis and insulinemia, and better glycemia maintenance during fasting in Walker-256 tumor rats on a diet supplemented with l-glutamine.


Assuntos
Caquexia/tratamento farmacológico , Suplementos Nutricionais , Duodeno/enzimologia , Glucose-6-Fosfatase/metabolismo , Glutamina/farmacologia , Jejuno/enzimologia , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Animais , Glicemia/metabolismo , Carcinoma 256 de Walker , Corticosterona/sangue , Duodeno/metabolismo , Gluconeogênese , Insulina/sangue , Jejuno/metabolismo , Masculino , Modelos Animais , Ratos , Ratos Wistar , Ureia/sangue
9.
Braz. j. pharm. sci ; 52(4): 761-769, Oct.-Dec. 2016. tab
Artigo em Inglês | LILACS | ID: biblio-951870

RESUMO

ABSTRACT We developed a pre-clinical model in which to evaluate the impact of orally administered carbohydrates on postprandial blood glucose levels. For this purpose, we compared the effects of different carbohydrates with well-established glycemic indexes. We orally administered (gavage) increasing amounts (0.2, 0.4, 0.6, 0.8, and 1.0 g/kg) of sucrose and lactose to rats which had been fasted for 6 h or 15 h, respectively. In part of the experiments we administered frutose (gavagem). Three different models were compared for measuring postprandial blood glucose levels: a) evaluation of interstitial glucose concentrations by using a real time continuous glucose monitoring system; b) evaluation of glucose levels in blood obtained from the rat tail; c) evaluation of serum glucose levels in blood collected after decapitation. Our results showed that blood obtained from the tails of 15-h fasted rats was the best model in which to evaluate the effect of carbohydrates on postprandial blood glucose levels.


Assuntos
Animais , Masculino , Ratos , Administração Oral , Índice Glicêmico/genética , Avaliação do Impacto na Saúde/instrumentação , Carboidratos/análise , Carga Glicêmica/efeitos dos fármacos
10.
Nutrients ; 8(11)2016 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-27801862

RESUMO

Both high-carbohydrate diet (HCD) and high-fat diet (HFD) modulate liver fat accumulation and inflammation, however, there is a lack of data on the potential contribution of carbohydrates and lipids separately. For this reason, the changes in liver fatty acid (FA) composition in male Swiss mice fed with HCD or HFD were compared, at the time points 0 (before starting the diets), and after 7, 14, 28 or 56 days. Activities of stearoyl-CoA desaturase-1 (SCD-1), ∆-6 desaturase (D6D), elongases and de novo lipogenesis (DNL) were estimated. Liver mRNA expression of acetyl-CoA carboxylase 1 (ACC1) was evaluated as an additional indicator of the de novo lipogenesis. Myeloperoxidase activity, nitric oxide (NO) production, and mRNA expressions of F4/80, type I collagen, interleukin (IL)-6, IL-1ß, IL-10, and tumor necrosis factor-α (TNF-α) were measured as indication of the liver inflammatory state. The HCD group had more intense lipid deposition, particularly of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). This group also showed higher DNL, SCD-1, and D6D activities associated with increased NO concentration, as well as myeloperoxidase activity. Livers from the HFD group showed higher elongase activity, stored more polyunsaturated fatty acids (PUFAs) and had a lower omega-6/omega-3 fatty acid (n-6/n-3) ratio. In conclusion, liver lipid accumulation, fatty acids (FA) composition and inflammation were modulated by the dietary composition of lipids and carbohydrates. The HCD group had more potent lipogenic and inflammatory effects in comparison with HFD.


Assuntos
Dieta da Carga de Carboidratos/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Lipogênese , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Acetiltransferases/metabolismo , Animais , Biomarcadores/metabolismo , Progressão da Doença , Ácidos Graxos Dessaturases/metabolismo , Elongases de Ácidos Graxos , Regulação da Expressão Gênica , Mediadores da Inflamação/metabolismo , Fígado/enzimologia , Fígado/imunologia , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , RNA Mensageiro/metabolismo , Distribuição Aleatória , Estearoil-CoA Dessaturase/metabolismo
11.
Braz. j. pharm. sci ; 52(3): 567-574, July-Sept. 2016. tab
Artigo em Inglês | LILACS | ID: biblio-828271

RESUMO

ABSTRACT The effect of glutamine dipeptide (GDP) supplementation in patients with diabetic foot syndrome was evaluated. A total of 22 patients took part in the study. GDP was supplied in 10 g sachets, and was dissolved in water immediately before use, with ingestion once a day, after lunch or after dinner (20 g/day) over a period of 30 days. Quantification of foot insensitive areas, oxidative stress, blood cytokines, and biochemical, hematological and toxicological parameters was performed before and after GDP supplementation. We observed an increase in blood levels of interferon-α (P=0.023), interferon-γ (P=0.038), interleukin-4 (P=0.003), interleukin-6 (P=0.0025), interleukin-7 (P=0.028), interleukin-12 p40 (P=0.017), interleukin-13 (P=0.001), leukocytes (P=0.037), eosinophils (P=0.049), and typical lymphocytes (P<0.001) due to GDP administration. In addition, we observed a reduced number (P=0.048) of insensitive areas on the foot, and reduction (P=0.047) of fasting hyperglycemia. Patients also showed increased blood high density lipoprotein (P<0.01) and protein thiol groups (P=0.004). These favorable results were associated with the absence of renal and hepatic toxicity. These results are of clinical relevance, since supplementation with GDP over 30 days improved clinical responses in patients with diabetic foot syndrome.


Assuntos
Humanos , Pé Diabético , Suplementos Nutricionais/análise , Dipeptidases/análise , Glutamina/análise , Diabetes Mellitus Tipo 2/reabilitação
12.
Amino Acids ; 48(12): 2773-2784, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27539646

RESUMO

This study aimed to evaluate the intestinal mucosa of the duodenum and jejunum of Walker-256 tumor-bearing rats supplemented with L-glutamine. Thirty-two male 50-day-old Wistar rats (Rattus norvegicus) were randomly divided into four groups: control (C), control supplemented with 2 % L-glutamine (GC), Walker-256 tumor (WT), and Walker-256 tumor supplemented with 2 % L-glutamine (TWG). Walker-256 tumor was induced by inoculation viable tumor cells in the right rear flank. After 10 days, celiotomy was performed and duodenal and jejunal tissues were removed and processed. We evaluated the cachexia index, proliferation index, villus height, crypt depth, total height of the intestinal wall, and number of goblet cells by the technique of periodic acid-Schiff (PAS). Induction of Walker-256 tumor promoted a reduction of metaphase index in the TW group animals, which was accompanied by a reduction in the villous height and crypt depths, resulting in atrophy of the intestinal wall as well as increased PAS-positive goblet cells. Supplementation with L-glutamine reduced the tumor growth and inhibited the development of the cachectic syndrome in animals of the TWG group. Furthermore, amino acid supplementation promoted beneficial effects on the intestinal mucosa in the TWG animals through restoration of the number of PAS-positive goblet cells. Therefore, supplementation with 2 % L-glutamine exhibited a promising role in the prevention of tumor growth and cancer-associated cachexia as well as restoring the intestinal mucosa in the duodenum and jejunum of Walker-256 tumor-bearing rats.


Assuntos
Caquexia/dietoterapia , Suplementos Nutricionais , Glutamina/farmacologia , Neoplasias/dietoterapia , Animais , Caquexia/patologia , Carcinogênese/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Mucosa Intestinal/efeitos dos fármacos , Neoplasias/metabolismo , Neoplasias/patologia , Ratos
14.
Braz. arch. biol. technol ; 59: e16150085, 2016. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-951418

RESUMO

The acute effects of Glycine max (GM) on post prandial glycemia (PPG) in male Wistar rats were investigated. All substances were orally administered by gavage in overnight fasted animals. The elevation of PPG promoted by starch (1g/kg) was prevented by GM (2.5 mg/kg, 5.0 mg/kg, 7.5 mg/kg, 10.0 mg/kg, and 100.0 mg/kg). In conclusion GM showed potential antidiabetic effect.

15.
Cell Biochem Funct ; 33(4): 183-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25959621

RESUMO

Coffee is the main source of chlorogenic acid in the human diet, and it contains several chlorogenic acid isomers, of which the 5-caffeoylquinic acid (5-CQA) is the predominant isomer. Because there are no available data about the action of chlorogenic acids from instant coffee on hepatic glucose-6-phosphatase (G-6-Pase) activity and blood glucose levels, these effects were investigated in rats. The changes on G-6-Pase activity and liver glucose output induced by 5-CQA were also investigated. Instant coffee extract with high chlorogenic acids content (37.8%) inhibited (p < 0.05) the G-6-Pase activity of the hepatocyte microsomal fraction in a dose-dependent way (up to 53), but IV administration of this extract did not change the glycaemia (p > 0.05). Similarly, 5-CQA (1 mM) reduced (p < 0.05) the activity of microsomal G-6-Pase by about 40%, but had no effect (p > 0.05) on glucose output arising from glycogenolysis in liver perfusion. It was concluded that instant coffee extract with high content of chlorogenic acids inhibited hepatic G-6-Pase in vitro, but failed to reduce the glycaemia probably because the coffee chlorogenic acids did not reach enough levels within the hepatocytes to inhibit the G-6-Pase and reduce the liver glucose output.


Assuntos
Glicemia/metabolismo , Ácido Clorogênico/farmacologia , Café/química , Glucose-6-Fosfatase/antagonistas & inibidores , Microssomos Hepáticos/enzimologia , Extratos Vegetais/química , Ácido Quínico/análogos & derivados , Animais , Ácido Clorogênico/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Índice Glicêmico/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Ácido Quínico/química , Ácido Quínico/farmacologia , Ratos , Ratos Wistar
16.
BMC Gastroenterol ; 15: 3, 2015 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-25609418

RESUMO

BACKGROUND: The prevalence of obesity has increased at alarming rates, particularly because of the increased consumption of high-fat diets (HFDs). The influence of HFDs on intrinsic innervation and the intestinal wall has not been fully characterized. The aim of this study was to investigate the morpho-quantitative aspects of myenteric neurons and the wall of the small intestine in mice fed a HFD. METHODS: Swiss mice were fed a HFD (59% kcal from fat) or standard chow (9% Kcal from fat) for 8 weeks. Segments of the duodenum, jejunum, and ileum were subjected to histological processing for morpho-quantitative examination of the intestinal wall and mucosal cells, and immunohistochemistry was performed to evaluate myenteric neurons. The data for each segment were compared between the groups using an unpaired Student's t-test or an equivalent nonparametric test. RESULTS: The HFD increased body weight and visceral fat and decreased the length of the small intestine and the circumference of the ileum. In the duodenum, the HFD increased the density of the nitrergic subpopulation and decreased the area of nitrergic neurons and vasoactive intestinal peptide (VIP) varicosities. In the jejunum, the density of the nitrergic subpopulation was increased and the neuronal areas of the general population, nitrergic subpopulation and (VIP) varicosities were reduced. In the ileum, the density of the general population and nitrergic subpopulation were increased and the neuronal areas of the general population, nitrergic subpopulation and (VIP) varicosities were reduced. The morphometric parameters of the villi, crypts, muscular layer and total wall generally increased in the duodenum and jejunum and decreased in the ileum. In the duodenum and jejunum, the HFD promoted a decreased in the proportion of intraepithelial lymphocytes. In the ileum, the proportion of intraepithelial lymphocytes and goblet cells reduced, and the enteroendocrine cells increased. CONCLUSIONS: The high-fat diet induces changes in the myenteric innervation of the small intestine, intestinal wall and mucosal cells responsible for the secretion of hormones and maintenance of the protective intestinal barrier. The morpho-quantitative data provide a basis for further studies to clarify the influence of HFD in the motility, digestive and absorptive capacity, and intestinal barrier.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Mucosa Intestinal/patologia , Intestino Delgado/inervação , Intestino Delgado/patologia , Neurônios/química , Neurônios/patologia , Animais , Proliferação de Células , Duodeno/inervação , Duodeno/patologia , Duodeno/fisiopatologia , Células Enteroendócrinas , Células Caliciformes , Íleo/inervação , Íleo/patologia , Íleo/fisiopatologia , Mucosa Intestinal/fisiopatologia , Intestino Delgado/fisiopatologia , Jejuno/inervação , Jejuno/patologia , Jejuno/fisiopatologia , Contagem de Linfócitos , Masculino , Camundongos , Plexo Mientérico/patologia , Miosina Tipo V/análise , Neurônios Nitrérgicos/patologia , Obesidade/etiologia , Obesidade/patologia , Peptídeo Intestinal Vasoativo/análise
17.
J Med Food ; 18(6): 625-30, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25514381

RESUMO

The impact of cyclodextrins (CDs) on postprandial glycemic response employing the real-time continuous glucose monitoring system (RT-CGMS) was investigated. For this purpose, α-CD, ß-CD, γ-CD, HP-ß-CD, curdlan, and dextrin at doses of 10 and 100 mg/kg were orally administered in rats. The RT-CGMS was efficient to evaluate the impact of CDs on postprandial glycemia. The results showed that α-CD, ß-CD, dextrin, and curdlan did not reduce the glycemic response after the administration of starch. In contrast, the HP-ß-CD (100 mg/kg) attenuated the rise in glycemia. Moreover, the γ-CD blunts the postprandial glycemic excursion at doses of 10 and 100 mg/kg. Therefore, γ-CD could attenuate the rise in glycemia promoted by oral administration of starch. Considering that the treatment of postprandial hyperglycemia is necessary to prevent type 2 diabetes, this study opens the perspective of better control of postprandial glycemia by the addition of γ-CD in food.


Assuntos
Glicemia/metabolismo , Ciclodextrinas/uso terapêutico , Hiperglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Período Pós-Prandial , 2-Hidroxipropil-beta-Ciclodextrina , Animais , Ciclodextrinas/farmacologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/prevenção & controle , Hiperglicemia/sangue , Hipoglicemiantes/farmacologia , Masculino , Modelos Animais , Monitorização Fisiológica/métodos , Ratos Wistar , Amido/sangue , beta-Ciclodextrinas/farmacologia , beta-Ciclodextrinas/uso terapêutico , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/uso terapêutico
18.
Dig Dis Sci ; 60(4): 841-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25330870

RESUMO

BACKGROUND: Obesity is considered a risk factor for other chronic diseases, and diets rich in lipids can cause alterations in the intestinal functions. AIM: The aim of this study was to investigate the effects of a high-fat diet (HFD) on the myenteric plexus of the large intestine in mice. METHODS: Swiss mice were distributed into four groups: Control animals fed standard chow for 8 and 17 weeks (C8 and C17 groups) and hyperlipidic animals fed HFD for 8 and 17 weeks (Ob8 and Ob17 groups). Immunofluorescence was performed in the large intestine for the morphologic and quantitative analysis of neuronal populations. RESULTS: Animals in the Ob17 group exhibited increased body weight and visceral fat gain compared with the C17 group. The intestinal area was also reduced in the two Ob groups. In the proximal colon, the Ob17 group exhibited 16.1 % reduction of the general neuronal density and 33 % reduction of the VIP-immunoreactive (IR) subpopulation. The general neuronal density in the distal colon was reduced by 45 % in the Ob17 group, and the nNOS-IR density was reduced by 35 %. The morphometry of neuronal cell bodies in the Ob17 group exhibited a reduction of the neuronal area of all of the neuronal populations studied in the proximal colon, with a reduction of the subpopulations of nNOS-IR and VIP-IR neurons in the distal colon. CONCLUSIONS: The HFD caused neuronal loss in the myenteric plexus, and nitrergic neurons were more resilient. The changes were more pronounced in the distal colon after 17 weeks.


Assuntos
Colo/inervação , Dieta Hiperlipídica/efeitos adversos , Plexo Mientérico , Neurônios Nitrérgicos , Animais , Masculino , Camundongos , Peptídeo Intestinal Vasoativo
19.
Nutrients ; 6(10): 4520-30, 2014 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-25338272

RESUMO

We compared the effects of oral administration of high-dose or low-dose glutamine dipeptide (GDP), alanine (ALA), glutamine (GLN), and ALA + GLN on the blood availability of amino acids in rats submitted to insulin-induced hypoglycemia (IIH). Insulin detemir (1 U/kg) was intraperitoneally injected to produce IIH; this was followed by oral administration of GDP, GLN + ALA, GLN, or ALA. We observed higher blood levels of GLN, 30 min after oral administration of high-dose GDP (1000 mg/kg) than after administration of ALA (381 mg/kg) + GLN (619 mg/kg), GLN (619 mg/kg), or ALA (381 mg/kg). However, we did not observe the same differences after oral administration of low-dose GDP (100 mg/kg) compared with ALA (38.1 mg/kg) + GLN (61.9 mg/kg), GLN (61.9 mg/kg), or ALA (38.1 mg/kg). We also observed less liver catabolism of GDP compared to ALA and GLN. In conclusion, high-dose GDP promoted higher blood levels of GLN than oral ALA + GLN, GLN, or ALA. Moreover, the lower levels of liver catabolism of GDP, compared to ALA or GLN, contributed to the superior performance of high-dose GDP in terms of blood availability of GLN.


Assuntos
Alanina/administração & dosagem , Aminoácidos/sangue , Glutamina/administração & dosagem , Hipoglicemia/induzido quimicamente , Hipoglicemia/dietoterapia , Fígado/metabolismo , Administração Oral , Animais , Suplementos Nutricionais , Dipeptídeos/administração & dosagem , Insulina/administração & dosagem , Insulina/farmacologia , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
20.
Mol Cell Biochem ; 397(1-2): 97-107, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25096025

RESUMO

The inducible expression of the 70-kDa heat shock proteins (HSP70) is associated with homeostatically stressful situations. Stresses involving sympathetic nervous system (SNS) activation, including α1-adrenergic agonists and physical exercise, are capable of inducing HSP70 expression and release of the HSP70 inducible form, HSP72. However, whether hypoglycaemia is capable of influencing HSP70 status under a stressful situation such as insulin-induced hypoglycaemia (IIH), which also involves SNS activation, is unsettled. Hence, we decided to investigate whether the predominant signal for HSP70 expression and delivery into the blood comes from either low glucose, high insulin, or both during short-term IIH (STIIH) and long-term IIH (LTIIH). Our data indicated that low glucose level (up to 1.56 ± 0.14 mM), but not insulin, is the triggering factor responsible for a dramatic rise in HSP72 plasma concentrations (from 0.15 ± 0.01 in fed state to 0.77 ± 0.13 ng/mL during hypoglycaemic episodes). This was observed in parallel with up to 7-fold increases in interleukin-6 (IL-6) but not interleukin-10 (IL-10) or tumour necrosis factor-α (TNF-α) at STIIH. Together, the observations may suggest that HSP72 is released under hypoglycaemic conditions as a part of the homeostatic stress response, whereas at long-term, both hypoglycaemia and insulin may influence HSP72 expression in the liver, but not in kidneys. Secreted extracellular HSP72 (eHSP72) may be purely a danger signal to all the tissues of the body for the enhancement of immune and metabolic surveillance state or actively participates in glycaemic control under stressful situations.


Assuntos
Proteínas de Choque Térmico HSP72/sangue , Hipoglicemia/sangue , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Interleucina-10/sangue , Interleucina-6/sangue , Fígado/metabolismo , Fator de Necrose Tumoral alfa/sangue , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Masculino , Ratos , Ratos Wistar , Fatores de Tempo
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