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1.
J Agric Food Chem ; 69(35): 10114-10120, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34428895

RESUMO

Our previous study showed that lycopene reduced the absorption of cholesterol in Caco-2 cells through inhibiting Niemann-Pick C1-Like 1 (NPC1L1) expression. Herein, we aimed to explore whether lycopene supplementation can decrease cholesterol absorption in the intestine and prevent atherosclerosis progression in high-fat diet (HFD)-fed apolipoprotein E knockout (ApoE-/-) mice. Male ApoE-/- mice were fed a high-fat diet with or without lycopene for 19 weeks. Supplementation of lycopene markedly lowered serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Additionally, serum high-density lipoprotein cholesterol (HDL-C) levels were increased after lycopene administration. Lycopene also downregulated the expression of NPC1L1 and hepatocyte nuclear factor-1α (HNF-1α) in the small intestine. Furthermore, the Oil Red O staining of the aorta and aortic sinus showed that lycopene supplementation remarkably reduced atherosclerotic lesions. These results indicated that lycopene inhibited intestinal cholesterol absorption and protected against HFD-induced atherosclerosis through inhibiting HNF-1α and NPC1L1 expression. Lycopene exhibits a potential antiatherosclerotic effect through suppressing intestinal cholesterol absorption.


Assuntos
Apolipoproteínas E , Aterosclerose , Animais , Apolipoproteínas E/genética , Aterosclerose/genética , Aterosclerose/prevenção & controle , Células CACO-2 , Colesterol , Fator 1-alfa Nuclear de Hepatócito , Humanos , Absorção Intestinal , Licopeno , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
2.
Nutrients ; 13(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371872

RESUMO

The aim of this exploratory study was to investigate gastrointestinal tolerance and protein absorption markers with a new enteral peptide formula (PF) compared to an isocaloric enteral intact protein standard formula (SF) containing the same amount of protein in ICU patients. Patients admitted to a cardio-thoracic intensive care unit expected to receive tube feeding for ≥5 days were randomized to receive either PF (1.5 kcal/mL) or SF in a double-blind manner for ≤14 days. Twenty-six patients were randomized (13 SF and 13 PF) and 23 (12 SF and 11 PF) completed at least 5 days of product administration. There were no statistically significant differences between the feeds during the first 5 days of intervention for diarrhea (SF:3 (23%); PF:5 (39%), p = 0.388), vomiting (SF:1 (8%); PF:2 (15%), p = 0.549), constipation (SF:7 (54%), PF:3 (23%), p = 0.115), and high gastric residual volume (>500 mL: SF:1 (8%); PF: 2 (15%), p = 0.535). There were no differences in plasma amino acids or urinary markers of protein absorption and metabolism. In conclusion, no major differences were found in tolerability and protein absorption markers between the standard intact protein formula and the peptide formula.


Assuntos
Estado Terminal/terapia , Proteínas na Dieta/administração & dosagem , Nutrição Enteral , Alimentos Formulados , Absorção Intestinal , Valor Nutritivo , Hidrolisados de Proteína/administração & dosagem , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Proteínas na Dieta/efeitos adversos , Método Duplo-Cego , Ingestão de Energia , Nutrição Enteral/efeitos adversos , Feminino , Alimentos Formulados/efeitos adversos , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Hidrolisados de Proteína/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
3.
Nutrients ; 13(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34371976

RESUMO

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (LFD) improves both gastrointestinal (GI) symptoms and the psychological profile of patients with irritable bowel syndrome with diarrhea (IBS-D). The effects of 12 weeks of LFD on GI symptom and psychological profiles in relation to inflammation and the involvement of the intestinal barrier were studied in twenty IBS-D patients. The IBS Severity Scoring System, the Symptom Checklist-90-Revised, the Italian version of the 36-Item Short-Form Health Survey, the IBS-Quality of Life (QoL) questionnaire, and the Psychophysiological questionnaire were administered. The GI barrier function was assessed by sugar absorption test, the serum and fecal zonulin levels, and the serum levels of intestinal fatty-acid binding protein and diamine oxidase. Interleukins (ILs) and lipopolysaccharide (LPS) serum levels were evaluated along with dysbiosis. At the end of LFD, GI symptoms, psychological state (mainly anxiety, somatization, psychoticism, and interpersonal sensitivity), and QoL significantly improved in these patients. Simultaneously, an improvement in small intestinal permeability and intestinal mucosal integrity occurred, while IL-6, Il-10, LPS, and fermentative dysbiosis significantly decreased. The LFD can modify the immune-inflammatory features and enhance intestinal permeability and mucosal integrity, thus determining a concurrent improvement in the clinical and psychological conditions.


Assuntos
Dieta com Restrição de Carboidratos , Fermentação , Trato Gastrointestinal/fisiopatologia , Intestinos/fisiopatologia , Síndrome do Intestino Irritável/dietoterapia , Síndrome do Intestino Irritável/psicologia , Adulto , Diarreia/fisiopatologia , Dissacarídeos , Feminino , Humanos , Inflamação/fisiopatologia , Absorção Intestinal/fisiologia , Mucosa Intestinal/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Monossacarídeos , Oligossacarídeos , Polímeros/administração & dosagem , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários
4.
Nutrients ; 13(7)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34371983

RESUMO

The worldwide prevalence of metabolic diseases such as obesity, metabolic syndrome and type 2 diabetes shows an upward trend in recent decades. A characteristic feature of these diseases is hyperglycemia which can be associated with hyperphagia. Absorption of glucose in the small intestine physiologically contributes to the regulation of blood glucose levels, and hence, appears as a putative target for treatment of hyperglycemia. In fact, recent progress in understanding the molecular and cellular mechanisms of glucose absorption in the gut and its reabsorption in the kidney helped to develop a new strategy of diabetes treatment. Changes in blood glucose levels are also involved in regulation of appetite, suggesting that glucose absorption may be relevant to hyperphagia in metabolic diseases. In this review we discuss the mechanisms of glucose absorption in the small intestine in physiological conditions and their alterations in metabolic diseases as well as their relevance to the regulation of appetite. The key role of SGLT1 transporter in intestinal glucose absorption in both physiological conditions and in diabetes was clearly established. We conclude that although inhibition of small intestinal glucose absorption represents a valuable target for the treatment of hyperglycemia, it is not always suitable for the treatment of hyperphagia. In fact, independent regulation of glucose absorption and appetite requires a more complex approach for the treatment of metabolic diseases.


Assuntos
Regulação do Apetite , Glucose/metabolismo , Hiperglicemia/metabolismo , Absorção Intestinal/fisiologia , Doenças Metabólicas/metabolismo , Humanos , Hiperglicemia/etiologia , Intestino Delgado/metabolismo , Doenças Metabólicas/complicações , Transportador 1 de Glucose-Sódio/metabolismo
5.
Biomed Pharmacother ; 138: 111094, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311521

RESUMO

Currently, several studies propose that the dominant intestinal bacteria are core flora. Besides keeping the homeostasis of the intestinal environment, the intestinal microflora also plays a role in body metabolism, production of some vitamins, and control of barrier function. The study aimed to investigate the jejunum microbiota in diabetic rats as well as it's the relationship with Ceftriaxone sodium-mediated gut dysbiosis, diabetic parameters, and intestinal permeability. Thirty-two Wistar rats (Male) were enrolled and divided into four groups (A, B, C, and D; N = 8). Subsequently, T2DM was induced in C and D groups by HFD/STZ model and then gut dysbiosis in B and D groups via intragastric administration of Ceftriaxone sodium for two weeks. The food-water intake, body weight, fasting blood glucose, plasma insulin, HOMA-IR, intestinal permeability, and jejunum microbiota and it's histology were investigated. In this study, T2DM was associated with a significant decrease in the richness and diversity of jejunum microbiota, elevation in the intestinal permeability, and higher abundance of some opportunistic pathogens. Ceftriaxone sodium-induced gut dysbiosis declined food-water intake, damagedthe villi of jejunum tissue, increased intestinal permeability, and affected the diversity of jejunum microbiota. In diabetic rats, Ceftriaxone sodium-mediated gut dysbiosis also declined the abundance of someSCFAs bacteria and raised the abundant of some opportunistic bacteria such as Staphylococcus_sciuri. Interestingly, we found that several bacteria were negatively correlated with HOMA-IR, fasting blood glucose, body weight, and intestinal permeability. Overall, the study highlighted the jejunum microflora alterations in HFD/STZ diabetic rats and assessed the effect of Ceftriaxone sodium-induced gut dysbiosis on diabetic parameters, jejunum microbiota and histology, and intestinal permeability, which are of potential for further studies.


Assuntos
Antibacterianos/farmacologia , Bactérias/crescimento & desenvolvimento , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal , Jejuno/microbiologia , Animais , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Ceftriaxona/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Disbiose , Microbioma Gastrointestinal/efeitos dos fármacos , Absorção Intestinal , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Masculino , Permeabilidade , Ratos Wistar , Estreptozocina
6.
Molecules ; 26(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34206087

RESUMO

Polyphenolic and Terpenoids are potent natural antiparasitic compounds. This study aimed to identify new drug against Leishmania parasites, leishmaniasis's causal agent. A new in silico analysis was accomplished using molecular docking, with the Autodock vina program, to find the binding affinity of two important phytochemical compounds, Masticadienonic acid and the 3-Methoxycarpachromene, towards the trypanothione reductase as target drugs, responsible for the defense mechanism against oxidative stress and virulence of these parasites. There were exciting and new positive results: the molecular docking results show as elective binding profile for ligands inside the active site of this crucial enzyme. The ADMET study suggests that the 3-Methoxycarpachromene has the highest probability of human intestinal absorption. Through this work, 3-Methoxycarpachromene and Masticadienonic acid are shown to be potentially significant in drug discovery, especially in treating leishmaniasis. Hence, drug development should be completed with promising results.


Assuntos
Leishmania infantum/enzimologia , NADH NADPH Oxirredutases/antagonistas & inibidores , Compostos Fitoquímicos/farmacologia , Triterpenos/farmacologia , Domínio Catalítico/efeitos dos fármacos , Simulação por Computador , Avaliação Pré-Clínica de Medicamentos , Humanos , Absorção Intestinal , Leishmania infantum/efeitos dos fármacos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacocinética , Proteínas de Protozoários/antagonistas & inibidores , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/farmacocinética
7.
Int J Pharm ; 606: 120893, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34274456

RESUMO

Orally inhaled products (OIPs) are gaining increased attention, as pulmonary delivery is a preferred route for the treatment of various diseases. Yet, the field of inhalation biopharmaceutics is still in development phase. For a successful correlation between various in vitro data obtained during formulation characterization and in vivo performance, it is necessary to understand the impact of parameters such as solubility and dissolution of drugs. In this work, we used in vitro-in silico feedback-feedforward approach to gain a better insight into the biopharmaceutics behavior of inhaled Salbutamol Sulphate (SS) and Budesonide (BUD). The thorough characterization of the in vitro test media and the impact of different in vitro fluid components such as lipids and protein on the solubility of aforementioned drugs was studied. These results were subsequently used as an input into the developed in silico models to investigate potential PK parameter changes in vivo. Results revealed that media comprising lipids and albumin were the most biorelevant and impacted the solubility of BUD the most. On the contrary, no notable impact was seen in case of SS. The use of simple media such as phosphate buffer saline (PBS) might be sufficient to use in solubility studies of the highly soluble and permeable drugs. However, its use for the poorly soluble drugs is limited due to the greater potential for interactions within in vivo environment. The use of in silico tools showed that the model response varies, depending on the used media. Therefore, this work highlights the relevance of carefully selecting the media composition when investigating solubility and dissolution behavior, especially in the early phases of drug development and of poorly soluble drugs.


Assuntos
Modelos Biológicos , Preparações Farmacêuticas , Administração por Inalação , Administração Oral , Simulação por Computador , Absorção Intestinal , Pulmão , Solubilidade
8.
Food Funct ; 12(11): 4935-4946, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34100469

RESUMO

Novel protein-based nanovehicles offer alternatives to fat for delivery of lipophilic bioactives (nutraceuticals and drugs), yet they raise important questions regarding the bioavailability and absorption mechanism of the bioactive without fat. To provide answers, we chose vitamin D3 (VD3) as a model lipophilic-nutraceutical, re-assembled casein-micelles (rCM) as model protein-based nanovehicles, and non-fat yoghurt as a model food. We prepared three yoghurt formulations: 3% fat with VD3 dissolved in milk-fat, non-fat and 3% fat, both latter enriched with VD3 within rCM. Following in vitro digestion, VD3 retention and bioaccessibility were high (∼90% and ∼70%, respectively) in all formulations. VD3 uptake by Caco-2 cells was three-fold higher (p < 0.005) in the non-fat yoghurt enriched with VD3 in rCM compared with enriched fat-containing yoghurts. SR-BI, CD36 and NPC1L1 transporters were involved in VD3 absorption irrespective of the composition. Thus, our findings demonstrate that protein nanovehicles may improve VD3 bioavailability, without altering its absorption mechanism compared to that from fat.


Assuntos
Caseínas/química , Colecalciferol/farmacocinética , Lipídeos/administração & dosagem , Nanopartículas/química , Disponibilidade Biológica , Células CACO-2 , Colecalciferol/química , Suplementos Nutricionais , Composição de Medicamentos/métodos , Humanos , Absorção Intestinal , Micelas , Iogurte
9.
J Agric Food Chem ; 69(26): 7344-7352, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34132531

RESUMO

Lentinan (LNT), a typical triple helix ß-glucan extracted from Lentinus edodes, has been widely used as a functional food and an orally administered drug. However, its oral pharmacokinetics has been rarely reported. The aim of this work is to systematically study the pharmacokinetics and intestinal absorption mechanism of LNT after oral administration. Radioactive 99m-technetium (99mTc) was introduced to label LNT to determine the plasma concentration, tissue distribution, and excretion of the ß-glucan in rats after oral administration. The results confirmed the absorption of LNT, with the maximal plasma concentration reached at 1 h. 5-([4,6-Dichlorotriazin-2-yl]amino)fluorescein (DTAF) was used to label LNT to explore the absorption mechanism of LNT, utilizing both a Ussing chamber and a monolayer of Caco-2 cells. These transport assays showed that LNT could penetrate through the intestine and epithelial monolayer, which was mediated by macropinocytosis and clathrin-mediated endocytosis. These findings provide a pharmacokinetic reference for LNT and help provide a greater understanding of the absorption of ß-glucans in general.


Assuntos
Endocitose , Lentinano , Animais , Células CACO-2 , Clatrina , Humanos , Absorção Intestinal , Ratos
10.
J Agric Food Chem ; 69(27): 7593-7602, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34190554

RESUMO

The present study describes the development of a novel liposome nanocarrier system. The liposome was coated with Lactobacillus acidophilus CICC 6074 S-layer protein (SLP) to improve the intestinal absorption of the cholesterol-lowering peptide Leu-Gln-Pro-Glu (LQPE). The SLP-coated liposomes were prepared and characterized with morphology, particle size, zeta potential, membrane stability, Fourier transform infrared spectroscopy, and dual-channel surface plasma resonance. The results showed that SLP could successfully self-assemble on liposomes. Then, LQPE liposomes and SLP-coated LQPE liposomes (SLP-L-LQPE) were prepared. SLP-L-LQPE not only showed better sustained release properties and gastrointestinal tolerance in vitro but also increased the retention time in mice intestine. Transepithelial transport experiment indicates that the transshipment of LQPE increased significantly after being embedded by liposomes and coated with SLP. The research provides a theoretical basis for the study of SLP-coated liposomes and a potential drug delivery system for improving the intestinal absorption of peptides.


Assuntos
Absorção Intestinal , Lactobacillus acidophilus , Lipossomos , Peptídeos/metabolismo , Animais , Mucosa Intestinal/metabolismo , Lipossomos/metabolismo , Camundongos , Tamanho da Partícula
11.
AAPS PharmSciTech ; 22(5): 179, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34128132

RESUMO

With the limitation of solubility and dissolution rate of insoluble drugs, following oral administration, they would rifely prove poor and volatile bioavailability, which may fail to realize its therapeutic value. The drug nanocrystals are perceived as effective tactic for oral administration of insoluble drugs attributes to possess many prominent properties such as elevating dissolution rate and saturation solubility, high drug loading capacity, and improving oral bioavailability. Based on these advantages, the application of nanocrystals in oral drug delivery has acquired significant achievement, and so far more than 20 products of drug nanocrystals have been confirmed in the market. However, the oral absorption of drug nanocrystals is still facing huge challenges due to the limitation of many factors. Intrinsic properties of the drugs and complex physiological environment of the intestinal tract are the two most important factors affecting the oral bioavailability of drugs. In addition, the research on the multi-aspect mechanisms of nanocrystals promoting gastrointestinal absorption and bioavailability has been gradually deepened. In this review, we summarized recent advances of the nanocrystals delivered orally, and provided an overview to the research progress for crossing the intestinal tract transport mechanisms of the nanocrystals by some new research techniques. Meanwhile, the factors relevant to the transport of drug nanocrystals were also elaborated in detail. Graphical Abstract.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Absorção Intestinal/efeitos dos fármacos , Nanopartículas/administração & dosagem , Preparações Farmacêuticas/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Humanos , Absorção Intestinal/fisiologia , Nanopartículas/química , Nanopartículas/metabolismo , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Solubilidade
12.
Nutrients ; 13(5)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067622

RESUMO

The iron absorption process developsmainly in the proximal duodenum. This portion of the intestine is typically destroyed in celiac disease (CD), resulting in a reduction in absorption of iron and subsequent iron deficiency anemia (IDA). In fact, the most frequent extra-intestinal manifestation (EIM) of CD is IDA, with a prevalence between 12 and 82% (in relation with the various reports) in patients with new CD diagnosis. The primary treatment of CD is the gluten-free diet (GFD), which is associated with adequate management of IDA, if present. Iron replacement treatment historically has been based on oral products containing ferrous sulphate (FS). However, the absorption of FS is limited in patients with active CD and unpredictable in patients on a GFD. Furthermore, a poor tolerability of this kind of ferrous is particularly frequent in patients with CD or with other inflammatory bowel diseases. Normalization from anemic state typically occurs after at least 6 months of GFD, but the process can take up to 2 years for iron stores to replenish.


Assuntos
Anemia Ferropriva/dietoterapia , Doença Celíaca/dietoterapia , Dieta Livre de Glúten , Ferro/deficiência , Anemia Ferropriva/etiologia , Doença Celíaca/complicações , Doença Celíaca/fisiopatologia , Duodeno/fisiopatologia , Humanos , Absorção Intestinal/fisiologia , Ferro/metabolismo
13.
Nutrients ; 13(5)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065342

RESUMO

The effects of exercise on nutrient digestion and absorption in the intestinal tract are not well understood. A few studies have reported that exercise training increases the expression of molecules involved in carbohydrate digestion and absorption. Exercise was also shown to increase the blood concentration of glucagon-like peptide-2 (GLP-2), which regulates carbohydrate digestion and absorption in the small intestine. Therefore, we investigated the effects of exercise on the expression of molecules involved in intestinal digestion and absorption, including GLP-2. Six-week-old male mice were divided into a sedentary (SED) and low-intensity exercise (LEx) group. LEx mice were required to run on a treadmill (12.5 m/min, 1 h), whereas SED mice rested. All mice were euthanized 1 h after exercise or rest, and plasma, jejunum, ileum, and colon samples were collected, followed by analysis via IHC, EIA, and immunoblotting. The levels of plasma GLP-2 and the jejunum expression of the GLP-2 receptor, sucrase-isomaltase (SI), and glucose transporter 2 (GLUT2) were higher in LEx mice. Thus, we showed that acute low-intensity exercise affects the expression of molecules involved in intestinal carbohydrate digestion and absorption via GLP-2. Our results suggest that exercise might be beneficial for small intestine function in individuals with intestinal frailty.


Assuntos
Peptídeo 2 Semelhante ao Glucagon/metabolismo , Condicionamento Físico Animal/fisiologia , Corrida/fisiologia , Regulação para Cima/fisiologia , Animais , Digestão/fisiologia , Absorção Intestinal/fisiologia , Mucosa Intestinal/metabolismo , Intestinos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Modelos Animais
14.
J Med Chem ; 64(13): 9389-9403, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34152772

RESUMO

Models intended to predict intestinal absorption are an essential part of the drug development process. Although many models exist for capturing intestinal absorption, many questions still exist around the applicability of these models to drug types like "beyond rule of 5" (bRo5) and low absorption compounds. This presents a challenge as current models have not been rigorously tested to understand intestinal absorption. Here, we assembled a large, structurally diverse dataset of ∼1000 compounds with known in vitro, preclinical, and human permeability and/or absorption data. In silico (quantitative structure-activity relationship), in vitro (Caco-2), and in vivo (rat) models were statistically evaluated for predictive performance against this human intestinal absorption dataset. We expect this evaluation to serve as a resource for DMPK scientists and medicinal/computational chemists to increase their understanding of permeability and absorption model utility and applications for academia and industry.


Assuntos
Absorção Intestinal/efeitos dos fármacos , Modelos Biológicos , Preparações Farmacêuticas/química , Relação Quantitativa Estrutura-Atividade , Animais , Células CACO-2 , Permeabilidade da Membrana Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Ratos
15.
Nature ; 595(7866): 272-277, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34163067

RESUMO

Diet is a major factor that shapes the gut microbiome1, but the consequences of diet-induced changes in the microbiome for host pathophysiology remain poorly understood. We conducted a randomized human intervention study using a very-low-calorie diet (NCT01105143). Although metabolic health was improved, severe calorie restriction led to a decrease in bacterial abundance and restructuring of the gut microbiome. Transplantation of post-diet microbiota to mice decreased their body weight and adiposity relative to mice that received pre-diet microbiota. Weight loss was associated with impaired nutrient absorption and enrichment in Clostridioides difficile, which was consistent with a decrease in bile acids and was sufficient to replicate metabolic phenotypes in mice in a toxin-dependent manner. These results emphasize the importance of diet-microbiome interactions in modulating host energy balance and the need to understand the role of diet in the interplay between pathogenic and beneficial symbionts.


Assuntos
Bactérias/isolamento & purificação , Bactérias/metabolismo , Restrição Calórica , Dieta Redutora , Microbioma Gastrointestinal/fisiologia , Adiposidade , Animais , Bactérias/crescimento & desenvolvimento , Bactérias/patogenicidade , Toxinas Bacterianas/metabolismo , Ácidos e Sais Biliares/metabolismo , Peso Corporal , Clostridioides difficile/crescimento & desenvolvimento , Clostridioides difficile/isolamento & purificação , Clostridioides difficile/metabolismo , Metabolismo Energético , Humanos , Absorção Intestinal , Masculino , Camundongos , Nutrientes/metabolismo , Simbiose , Perda de Peso
16.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073709

RESUMO

Polyphenols are natural organic compounds produced by plants, acting as antioxidants by reacting with ROS. These compounds are widely consumed in daily diet and many studies report several benefits to human health thanks to their bioavailability in humans. However, the digestion process of phenolic compounds is still not completely clear. Moreover, bioavailability is dependent on the metabolic phase of these compounds. The LogP value can be managed as a simplified measure of the lipophilicity of a substance ingested within the human body, which affects resultant absorption. The biopharmaceutical classification system (BCS), a method used to classify drugs intended for gastrointestinal absorption, correlates the solubility and permeability of the drug with both the rate and extent of oral absorption. BCS may be helpful to measure the bioactive constituents of foods, such as polyphenols, in order to understand their nutraceutical potential. There are many literature studies that focus on permeability, absorption, and bioavailability of polyphenols and their resultant metabolic byproducts, but there is still confusion about their respective LogP values and BCS classification. This review will provide an overview of the information regarding 10 dietarypolyphenols (ferulic acid, chlorogenic acid, rutin, quercetin, apigenin, cirsimaritin, daidzein, resveratrol, ellagic acid, and curcumin) and their association with the BCS classification.


Assuntos
Produtos Biológicos/metabolismo , Polifenóis/metabolismo , Animais , Disponibilidade Biológica , Produtos Biológicos/química , Produtos Biológicos/classificação , Produtos Biológicos/farmacocinética , Ácidos Cumáricos , Flavonas , Flavonóis , Humanos , Absorção Intestinal , Isoflavonas , Permeabilidade , Polifenóis/química , Polifenóis/classificação , Polifenóis/farmacocinética , Solubilidade , Estilbenos , Taninos
17.
Int J Mol Sci ; 22(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071110

RESUMO

Rectal drug delivery is an effective alternative to oral and parenteral treatments. This route allows for both local and systemic drug therapy. Traditional rectal dosage formulations have historically been used for localised treatments, including laxatives, hemorrhoid therapy and antipyretics. However, this form of drug dosage often feels alien and uncomfortable to a patient, encouraging refusal. The limitations of conventional solid suppositories can be overcome by creating a thermosensitive liquid suppository. Unfortunately, there are currently only a few studies describing their use in therapy. However, recent trends indicate an increase in the development of this modern therapeutic system. This review introduces a novel rectal drug delivery system with the goal of summarising recent developments in thermosensitive liquid suppositories for analgesic, anticancer, antiemetic, antihypertensive, psychiatric, antiallergic, anaesthetic, antimalarial drugs and insulin. The report also presents the impact of various types of components and their concentration on the properties of this rectal dosage form. Further research into such formulations is certainly needed in order to meet the high demand for modern, efficient rectal gelling systems. Continued research and development in this field would undoubtedly further reveal the hidden potential of rectal drug delivery systems.


Assuntos
Administração Retal , Géis/administração & dosagem , Preparações Farmacêuticas/administração & dosagem , Supositórios/administração & dosagem , Resinas Acrílicas/química , Alginatos/química , Temperatura Corporal , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Previsões , Géis/química , Temperatura Alta , Humanos , Absorção Intestinal , Metilcelulose/química , Poloxâmero/química , Povidona/química , Supositórios/química
18.
Nutr Clin Pract ; 36(4): 853-862, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34101267

RESUMO

OBJECTIVE: Gastrointestinal (GI) dysfunction is prevalent in critically ill patients with coronavirus disease 2019 (COVID-19). The acetaminophen absorption test (AAT) has been previously described as a direct method for assessment of GI function. Our study determines whether the AAT can be used to assess GI function in critically ill COVID-19 patients, compared with traditional measures of GI function. DESIGN: Retrospective observational study of critically ill patients with COVID-19. SETTING: Three intensive care units at a tertiary care academic medical center. PATIENTS: Twenty critically ill patients with COVID-19. INTERVENTIONS: The results of AAT and traditional measures for assessing GI function were collected and compared. MEASUREMENTS AND MAIN RESULTS: Among the study cohort, 55% (11 of 20) of patients had evidence of malabsorption by AAT. Interestingly, all patients with evidence of malabsorption by AAT had clinical evidence of bowel function, as indicated by stool output and low gastric residuals during the prior 24 h. When comparing patients with a detectable acetaminophen level (positive AAT) with those who had undetectable acetaminophen levels (negative AAT), radiologic evidence of ileus was less frequent (20 vs 88%; P = .03), tolerated tube-feed rates were higher (40 vs 10 ml/h; P =.01), and there was a trend toward lower gastric residual volumes (45 vs 830 ml; P =.11). CONCLUSION: Malabsorption can occur in critically ill patients with COVID-19 despite commonly used clinical indicators of tube-feeding tolerance. The AAT provides a simple, rapid, and cost-effective mechanism by which enteral function can be efficiently assessed in COVID-19 patients.


Assuntos
Acetaminofen , COVID-19 , Estado Terminal , Humanos , Absorção Intestinal , Estudos Retrospectivos , SARS-CoV-2
19.
Acta Physiol (Oxf) ; 233(1): e13694, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34031986

RESUMO

AIM: Absorption of ammonia from the gut has consequences that range from encephalitis in hepatic disease to global climate change induced by nitrogenous excretions from livestock. Since patch clamp data show that certain members of the transient receptor potential (TRP) family are permeable to NH4 + , participation in ammonium efflux was investigated. METHODS: Digesta, mucosa and muscular samples from stomach, duodenum, jejunum, ileum, caecum and colon of pigs were analysed via colourimetry, qPCR, Western blot, immunohistochemistry and Ussing chambers. RESULTS: qPCR data show high duodenal expression of TRPV6. TRPM6 was highest in jejunum and colon, with expression of TRPM7 ubiquitous. TRPM8 and TRPV1 were below detection. TRPV2 was highest in the jejunum but almost non-detectable in the colon. TRPV4 was ubiquitously expressed by mucosal and muscular layers. TRPV3 mRNA was only found in the mucosa of the caecum and colon, organs in which NH4 + was highest (>7 mmol·L-1 ). Immunohistochemically, an apical expression of TRPV3 and TRPV4 could be detected in all tissues, with effects of 2-APB and GSK106790A supporting functional expression. In symmetrical NaCl Ringer, removal of mucosal Ca2+ and Mg2+ increased colonic short circuit current (Isc ) and conductance (Gt ) by 0.18 ± 0.06 µeq·cm-2 ·h-1 and 4.70 ± 0.85 mS·cm-2 (P < .05, N/n = 4/17). Application of mucosal NH4 Cl led to dose-dependent and divalent-sensitive increases in Gt and Isc , with effects highest in the caecum and colon. CONCLUSION: We propose that TRP channels contribute to the intestinal transport of ammonium, with TRPV3 and TRPV4 promising candidate proteins. Pharmacological regulation may be possible.


Assuntos
Compostos de Amônio , Canais de Potencial de Receptor Transitório , Animais , Transporte Biológico , Absorção Intestinal , Suínos , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo
20.
Toxicol Appl Pharmacol ; 422: 115560, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33957192

RESUMO

Antipsychotic polypharmacy (APP), as one maintenance treatment strategy in patients with schizophrenia, has gained popularity in real-world clinical settings. Risperidone (RIS) and clozapine (CLZ) are the most commonly prescribed second-generation antipsychotics, and they are often used in combination as APP. In this study, the pharmacokinetics of RIS and CLZ in rats were examined after co-administration to explore the reliability and rationality of co-medication with RIS and CLZ. In addition, the effects of CLZ on RIS metabolism and transport in vitro were investigated. The results illustrated that in the 7-day continuous administration test in rats, when co-administered with CLZ, the area under curve and peak concentrations of RIS were increased by 2.2- and 3.1-fold at the first dose, respectively, increased by 3.4- and 6.2-fold at the last dose, respectively. The metabolite-to-parent ratio of RIS was approximately 22% and 33% lower than those of RIS alone group at the first and last doses, respectively. Moreover, CLZ significantly increased RIS concentrations in the brain (3.0-4.8 folds) and cerebrospinal fluid (2.1-3.5 folds) in rats, which was slightly lower than the impact of verapamil on RIS after co-medication. Experiments in vitro indicated that CLZ competitively inhibited the conversion of RIS to 9-hydroxy-RIS with the inhibition constants of 1.36 and 3.0 µM in rat and human liver microsomes, respectively. Furthermore, the efflux ratio of RIS in Caco-2 monolayers was significantly reduced by CLZ at 1 µM. Hence, CLZ may affect the exposure of RIS by inhibiting its metabolism and P-glycoprotein-mediated transport. These findings highlighted that APP with RIS and CLZ might increase the plasma concentrations of RIS and 9-hydroxy-RIS beyond the safety ranges and cause toxic side effects.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Antipsicóticos/farmacocinética , Clozapina/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Microssomos Hepáticos/efeitos dos fármacos , Risperidona/farmacocinética , Animais , Antipsicóticos/toxicidade , Biotransformação , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Células CACO-2 , Clozapina/toxicidade , Interações Medicamentosas , Humanos , Mucosa Intestinal/metabolismo , Masculino , Microssomos Hepáticos/metabolismo , Ratos Sprague-Dawley , Medição de Risco , Risperidona/toxicidade , Distribuição Tecidual
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