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https://www.readbyqxmd.com/read/28541045/orally-absorbed-cyclic-peptides
#1
Daniel S Nielsen, Nicholas E Shepherd, Weijun Xu, Andrew J Lucke, Martin J Stoermer, David P Fairlie
Peptides and proteins are not orally bioavailable in mammals, although a few peptides are intestinally absorbed in small amounts. Polypeptides are generally too large and polar to passively diffuse through lipid membranes, while most known active transport mechanisms facilitate cell uptake of only very small peptides. Systematic evaluations of peptides with molecular weights above 500 Da are needed to identify parameters that influence oral bioavailability. Here we describe 125 cyclic peptides containing four to thirty-seven amino acids that are orally absorbed by mammals...
May 25, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28540173/self-microemulsifying-drug-delivery-system-for-improving-the-bioavailability-of-huperzine-a-by-lymphatic-uptake
#2
Fang Li, Rongfeng Hu, Bin Wang, Yun Gui, Gang Cheng, Song Gao, Lei Ye, Jihui Tang
Huperzine A (Hup-A) is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration-time curve (AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (P<0...
May 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28540164/understanding-peroral-absorption-regulatory-aspects-and-contemporary-approaches-to-tackling-solubility-and-permeability-hurdles
#3
REVIEW
Prachi B Shekhawat, Varsha B Pokharkar
Oral drug absorption is a process influenced by the physicochemical and biopharmaceutical properties of the drug and its inter-relationship with the gastrointestinal tract. Drug solubility, dissolution and permeability across intestinal barrier are the key parameters controlling absorption. This review provides an overview of the factors that affect drug absorption and the classification of a drug on the basis of solubility and permeability. The biopharmaceutical classification system (BCS) was introduced in early 90׳s and is a regulatory tool used to predict bioavailability problems associated with a new entity, thereby helping in the development of a drug product...
May 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28539272/selenium-nanoparticles-as-versatile-carriers-for-oral-delivery-of-insulin-insight-into-the-synergic-antidiabetic-effect-and-mechanism
#4
Wenji Deng, Qian Xie, Huan Wang, Zhiguo Ma, Baojian Wu, Xingwang Zhang
Oral insulin delivery has been plagued by limited bioavailability. This work reports selenium nanoparticles (SeNPs) for oral insulin delivery to overcome the absorption barrier. Insulin-loaded SeNPs (INS-SeNPs) were fabricated by ionic cross-linking/in situ reduction and characterized by particle size and drug entrapment. The resultant INS-SeNPs were 120nm around in particle size with high drug loading. INS-SeNPs exhibited controllable insulin release and outstanding stability in the digestive fluids. INS-SeNPs caused a significant hypoglycemic effect in both normal and diabetic rats...
May 21, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28538678/effects-of-commercial-apple-varieties-on-human-gut-microbiota-composition-and-metabolic-output-using-an-in-vitro-colonic-model
#5
Athanasios Koutsos, Maria Lima, Lorenza Conterno, Mattia Gasperotti, Martina Bianchi, Francesca Fava, Urska Vrhovsek, Julie A Lovegrove, Kieran M Tuohy
Apples are a rich source of polyphenols and fiber. A major proportion of apple polyphenols escape absorption in the small intestine and together with non-digestible polysaccharides reach the colon, where they can serve as substrates for bacterial fermentation. Animal studies suggest a synergistic interaction between apple polyphenols and the soluble fiber pectin; however, the effects of whole apples on human gut microbiota are less extensively studied. Three commercial apple varieties-Renetta Canada, Golden Delicious and Pink Lady-were digested and fermented in vitro using a batch culture colonic model (pH 5...
May 24, 2017: Nutrients
https://www.readbyqxmd.com/read/28536535/role-of-intestinal-lxr%C3%AE-in-regulating-post-prandial-lipid-excursion-and-diet-induced-hypercholesterolemia-and-hepatic-lipid-accumulation
#6
Tibiábin Benítez-Santana, Sarah E Hugo, Amnon Schlegel
Post-prandial hyperlipidemia has emerged as a cardiovascular risk factor with limited therapeutic options. The Liver X receptors (Lxrs) are nuclear hormone receptors that regulate cholesterol elimination. Knowledge of their role in regulating the absorption and handling of dietary fats is incomplete. The purpose of this study was to determine the role of intestinal Lxrα in post-prandial intestinal lipid transport. Using Lxrα knockout (nr1h3(-/-)) and intestine-limited Lxrα over-expressing [Tg(fabp2a:EGFP-nr1h3)] zebrafish strains, we measured post-prandial lipid excursion with live imaging in larvae and physiological methods in adults...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28536318/-the-intestinal-stem-cell-system
#7
Fumiaki Ishibashi, Ryuichi Okamoto, Mamoru Watanabe
The intestinal epithelium harbors stem cells at the bottom of crypts. Intestinal stem cells(ISCs)differentiate toward two alternative lineages of secretory or absorptive cells in a unidirectional manner. Studies have revealed factors that are indispensable for maintaining proliferation and differentiation of ISCs, which are provided from the surrounding environment. Additionally, several back-up systems compensating the sudden and massive loss of the ISC pool has been reported. Recent development of the three-dimensional culture system of ISCs in vitro has greatly contributed to elucidate these functional analyses of ISCs...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28535520/phosphate-in-chronic-kidney-disease-progression
#8
Mario Cozzolino, Denis Foque, Paola Ciceri, Andrea Galassi
A direct and independent association between serum phosphate (P) levels and mortality has been reported. High circulating P concentrations, still within the normal range, was associated with unfavourable outcomes in normal subjects as well as in chronic kidney disease (CKD) patients. Experimental data support the notion that P overload may hamper survival expectancy, directly inducing vascular, skeletal, and renal ageing. The balance of P results from dietary intake, intestinal absorption, glomerular filtration, tubular resorption, and hormonal asset...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28534300/formulation-and-evaluation-of-naringenin-nanosuspensions-for-bioavailability-enhancement
#9
Sonia Gera, Sreekanth Talluri, Nagarjun Rangaraj, Sunitha Sampathi
The clinical potential of naringenin (NRG) is compromised due to its poor aqueous solubility and low oral bioavailability. The study is aimed at addressing these issues by means of naringenin nanosuspensions (NRG-NS) formulated using polyvinylpyrrolidone (PVP K-90) as stabiliser via antisolvent sonoprecipitation method. Optimisation of sonication time, drug concentration and stabilisers was done based on particle size. Characterisation of pure NRG and NRG-NS was carried out by scanning electron microscopy, differential scanning calorimetry (DSC), x-ray powder diffractometry (XRD) and Fourier transform infrared spectroscopy (FTIR)...
May 22, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28533680/preparation-characterization-and-in-vitro-vivo-studies-of-oleanolic-acid-loaded-lactoferrin-nanoparticles
#10
Xiaojing Xia, Haowei Liu, Huixia Lv, Jing Zhang, Jianping Zhou, Zhiying Zhao
Oleanolic acid (OA), a pentacyclic triterpene, is used to safely and economically treat hepatopathy. However, OA, a Biopharmaceutics Classification System IV category drug, has low bioavailability owing to low solubility (<1 μg/mL) and biomembrane permeability. We developed a novel OA nanoparticle (OA-NP)-loaded lactoferrin (Lf) nanodelivery system with enhanced in vitro OA dissolution and improved oral absorption and bioavailability. The OA-NPs were prepared using NP albumin-bound technology and characterized using dynamic light scattering, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and in vitro dissolution test...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28531145/the-occurrence-biosynthesis-and-molecular-structure-of-proanthocyanidins-and-their-effects-on-legume-forage-protein-precipitation-digestion-and-absorption-in-the-ruminant-digestive-tract
#11
REVIEW
Arjan Jonker, Peiqiang Yu
Forages grown in temperate regions, such as alfalfa (Medicago sativa L.) and white clover (Trefolium repens L.), typically have a high nutritional value when fed to ruminants. Their high protein content and degradation rate result, however, in poor utilization of protein from the forage resulting in excessive excretion of nitrogen into the environment by the animal. Proanthocyanindins (also known as condensed tannins) found in some forage legumes such as birdsfoot trefoil (Lotus corniculatus L.), bind to dietary protein and can improve protein utilization in the animal...
May 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28528740/angubindin-1-a-novel-paracellular-absorption-enhancer-acting-at-the-tricellular-tight-junction
#12
Susanne M Krug, Tomohiro Hayaishi, Daisuke Iguchi, Akihiro Watari, Azusa Takahashi, Michael Fromm, Masahiro Nagahama, Hiroyuki Takeda, Yoshiaki Okada, Tatsuya Sawasaki, Takefumi Doi, Kiyohito Yagi, Masuo Kondoh
A limiting barrier for mucosal absorption of drugs is the tight junction (TJ). TJs exist between two adjacent cells (bicellular TJ, bTJ) and at the sites where three cells meet (tricellular TJ, tTJ). We present a novel approach which employs a physiologically regulated pathway for the passage of large molecules through the tTJ. Main barrier-relevant tTJ proteins are tricellulin and angulin-1 to -3. We developed an angulin binder from Clostridium perfringens iota-toxin (Ib) whose receptor is angulin-1. An Ib fragment corresponding to amino acids 421-664 (Ib421-664) of iota-toxin proved to bind in cells expressing angulin-1 and -3, but not angulin-2...
May 18, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28528581/organic-zinc-absorption-by-the-intestine-of-broilers-in-vivo
#13
Yu Yu, Lin Lu, Su-Fen Li, Li-Yang Zhang, Xu-Gang Luo
In Expt 1, a Zn-unsupplemented basal diet (control) and the basal diet supplemented with one of four different Zn sources, including ZnSO4, Zn-amino acid chelate with a weak chelation strength (Zn-AA W), Zn-protein chelate with a moderate chelation strength (Zn-Pro M) and Zn-protein chelate with a strong chelation strength (Zn-Pro S) were fed to broiler chickens from days 14 to 28. On day 28, Zn content in plasma from the hepatic portal vein increased (P0·05) and Zn-AA W(P<0·04) were higher than those for ZnSO4...
May 22, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28527897/advanced-glycation-endproducts-form-during-ovalbumin-digestion-in-the-presence-of-fructose-inhibition-by-chlorogenic-acid
#14
Yasmin Bains, Alejandro Gugliucci, Russell Caccavello
BACKGROUND: One mechanism by which fructose could exert deleterious effects is through intestinal formation and absorption of pro-inflammatory advanced glycation endproducts via the Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin (OVA) to test the hypothesis that advanced glycation endproducts (AGEs) are formed by fructose during simulated digestion of a ubiquitous food protein under model physiological conditions. METHODS: OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100mM)...
May 17, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28527800/from-pre-to-postweaning-transformation-of-the-young-calf-s-gastrointestinal-tract
#15
Sarah J Meale, Frederique Chaucheyras-Durand, Harma Berends, Le Luo Guan, Michael A Steele
The ruminant gastrointestinal tract (GIT) faces the challenge of protecting the host from luminal contents and pathogens, while supporting the absorption and metabolism of nutrients for growth and maintenance. The GIT of the calf in early life undergoes some of the most rapid microbial and structural changes documented in nature, and these adaptations in GIT function make the young calf susceptible to GIT diseases and disorders. Despite these challenges, the calf's GIT has a certain degree of plasticity and can sense nutrient supply and respond to bioactive ingredients...
May 17, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28526688/loss-of-the-anion-exchanger-dra-slc26a3-or-pat1-slc26a6-alters-sulfate-transport-by-the-distal-ileum-and-overall-sulfate-homeostasis
#16
Jonathan M Whittamore, Marguerite Hatch
The ileum is considered the primary site of inorganic sulfate (SO4(2-)) absorption. In the present study, we explored the contributions of the apical chloride/bicarbonate (Cl(-)/HCO3(-)) exchangers DRA (Slc26a3), and PAT1 (Slc26a6), to the underlying transport mechanism. Transepithelial (35)SO4(2-) and (36)Cl(-) fluxes were determined across isolated, short-circuited segments of the distal ileum from wild-type (WT), DRA-knockout (KO) and PAT1-KO mice, together with measurements of urine and plasma sulfate. The WT distal ileum supported net sulfate absorption (197...
May 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28524627/weight-loss-interventions-and-gut-microbiota-changes-in-overweight-and-obese-patients-a-systematic-review
#17
REVIEW
F B Seganfredo, C A Blume, M Moehlecke, A Giongo, D S Casagrande, J V N Spolidoro, A V Padoin, B D Schaan, C C Mottin
Imbalances in the gut microbiota, the bacteria that inhabit the intestines, are central to the pathogenesis of obesity. This systematic review assesses the association between the gut microbiota and weight loss in overweight/obese adults and its potential manipulation as a target for treating obesity. This review identified 43 studies using the keywords 'overweight' or 'obesity' and 'microbiota' and related terms; among these studies, 17 used dietary interventions, 11 used bariatric surgery and 15 used microbiota manipulation...
May 19, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28522903/oxidative-stress-antioxidants-and-intestinal-calcium-absorption
#18
REVIEW
Gabriela Diaz de Barboza, Solange Guizzardi, Luciana Moine, Nori Tolosa de Talamoni
The disequilibrium between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their elimination by protective mechanisms leads to oxidative stress. Mitochondria are the main source of ROS as by-products of electron transport chain. Most of the time the intestine responds adequately against the oxidative stress, but with aging or under conditions that exacerbate the ROS and/or RNS production, the defenses are not enough and contribute to developing intestinal pathologies. The endogenous antioxidant defense system in gut includes glutathione (GSH) and GSH-dependent enzymes as major components...
April 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28521167/in-vitro-bioaccessibility-of-five-pyrethroids-after-human-ingestion-and-the-corresponding-gastrointestinal-digestion-parameters-a-contribution-for-human-exposure-assessments
#19
Yan-Hong Shi, Jin-Jing Xiao, Rong-Peng Feng, Yu-Ying Liu, Min Liao, Xiang-Wei Wu, Ri-Mao Hua, Hai-Qun Cao
Bioaccessibility is a crucial parameter in assessing the absorption of contaminants during the human digestive process, but few studies have involved the differences in the bioaccessibilities of pesticides. To investigate the mode of using the in vitro bioaccessibility to refine estimates of dietary exposure to pesticide residues, this study measured the bioaccessibilities of five pyrethroids in apples, and then, it modelled physicochemical predictors (gastrointestinal pH, digestive times, and the solid-liquid (S/L) ratio) of the bioaccessibilities of pyrethroids...
May 15, 2017: Chemosphere
https://www.readbyqxmd.com/read/28515067/relative-contribution-of-%C3%AE-carotene-to-postprandial-vitamin-a-concentrations-in-healthy-humans-after-carrot-consumption
#20
Jessica L Cooperstone, Hilary J Goetz, Ken M Riedl, Earl H Harrison, Steven J Schwartz, Rachel E Kopec
Background: Asymmetric α-carotene, a provitamin A carotenoid, is cleaved to produce retinol (vitamin A) and α-retinol (with negligible vitamin A activity). The vitamin A activity of α-carotene-containing foods is likely overestimated because traditional analytic methods do not separate α-retinol derivatives from active retinol.Objective: This study aimed to accurately characterize intestinal α-carotene cleavage and its relative contribution to postprandial vitamin A in humans after consumption of raw carrots...
May 17, 2017: American Journal of Clinical Nutrition
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