0
selected
-
1.
Quantitative prediction of pharmacokinetic properties of drugs in humans: Recent advance in in vitro models to predict the impact of efflux transporters in the small intestine and blood-brain barrier.
Hashimoto, Y, Michiba, K, Maeda, K, Kusuhara, H
Journal of pharmacological sciences. 2022;(1):142-151
Abstract
Efflux transport systems are essential to suppress the absorption of xenobiotics from the intestinal lumen and protect the critical tissues at the blood-tissue barriers, such as the blood-brain barrier. The function of drug efflux transport is dominated by various transporters. Accumulated clinical evidences have revealed that genetic variations of the transporters, together with coadministered drugs, affect the expression and/or function of transporters and subsequently the pharmacokinetics of substrate drugs. Thus, in the preclinical stage of drug development, quantitative prediction of the impact of efflux transporters as well as that of uptake transporters and metabolic enzymes on the pharmacokinetics of drugs in humans has been performed using various in vitro experimental tools. Various kinds of human-derived cell systems can be applied to the precise prediction of drug transport in humans. Mathematical modeling consisting of each intrinsic metabolic or transport process enables us to understand the disposition of drugs both at the organ level and at the level of the whole body by integrating a variety of experimental results into model parameters. This review focuses on the role of efflux transporters in the intestinal absorption and brain distribution of drugs, in addition to recent advances in predictive tools and methodologies.
-
2.
Small and Large Intestine (II): Inflammatory Bowel Disease, Short Bowel Syndrome, and Malignant Tumors of the Digestive Tract.
Ber, Y, García-Lopez, S, Gargallo-Puyuelo, CJ, Gomollón, F
Nutrients. 2021;(7)
Abstract
The small intestine is key in the digestion and absorption of macro and micronutrients. The large intestine is essential for the absorption of water, to allow adequate defecation, and to harbor intestinal microbiota, for which their nutritional role is as important as it is unknown. This article will describe the causes and consequences of malnutrition in patients with inflammatory bowel diseases, the importance of screening and replacement of micronutrient deficits, and the main indications for enteral and parenteral nutrition in these patients. We will also discuss the causes of short bowel syndrome, a complex entity due to anatomical or functional loss of part of the small bowel, which can cause insufficient absorption of liquid, electrolytes, and nutrients and lead to complex management. Finally, we will review the causes, consequences, and management of malnutrition in patients with malignant and benign digestive tumors, including neuroendocrine tumors (present not only in the intestine but also in the pancreas).
-
3.
Small Intestinal Bacterial Overgrowth as Potential Therapeutic Target in Parkinson's Disease.
Dănău, A, Dumitrescu, L, Lefter, A, Tulbă, D, Popescu, BO
International journal of molecular sciences. 2021;(21)
Abstract
Increasing evidence suggests that the gut microbiota and the brain are closely connected via the so-called gut-brain axis. Small intestinal bacterial overgrowth (SIBO) is a gut dysbiosis in which the small intestine is abundantly colonized by bacteria that are typically found in the colon. Though not a disease, it may result in intestinal symptoms caused by the accumulation of microbial gases in the intestine. Intestinal inflammation, malabsorption and vitamin imbalances may also develop. SIBO can be eradicated by one or several courses of antibiotics but reappears if the predisposing condition persists. Parkinson's disease (PD) is a common neurodegenerative proteinopathy for which disease modifying interventions are not available. Sporadic forms may start in the gut years before the development of clinical features. Increased gastrointestinal transit time is present in most people with PD early during the course of the disease, predisposing to gut dysbiosis, including SIBO. The role that gut dysbiosis may play in the etiopathogenesis of PD is not fully understood yet. Here, we discuss the possibility that SIBO could contribute to the progression of PD, by promoting or preventing neurodegeneration, thus being a potential target for treatments aiming at slowing down the progression of PD. The direct symptomatic impact of SIBO and its impact on symptomatic medication are also briefly discussed.
-
4.
A Guide to Human Zinc Absorption: General Overview and Recent Advances of In Vitro Intestinal Models.
Maares, M, Haase, H
Nutrients. 2020;(3)
Abstract
Zinc absorption in the small intestine is one of the main mechanisms regulating the systemic homeostasis of this essential trace element. This review summarizes the key aspects of human zinc homeostasis and distribution. In particular, current knowledge on human intestinal zinc absorption and the influence of diet-derived factors on bioaccessibility and bioavailability as well as intrinsic luminal and basolateral factors with an impact on zinc uptake are discussed. Their investigation is increasingly performed using in vitro cellular intestinal models, which are continually being refined and keep gaining importance for studying zinc uptake and transport via the human intestinal epithelium. The vast majority of these models is based on the human intestinal cell line Caco-2 in combination with other relevant components of the intestinal epithelium, such as mucin-secreting goblet cells and in vitro digestion models, and applying improved compositions of apical and basolateral media to mimic the in vivo situation as closely as possible. Particular emphasis is placed on summarizing previous applications as well as key results of these models, comparing their results to data obtained in humans, and discussing their advantages and limitations.
-
5.
Microbial Profiles of Cirrhosis in the Human Small Intestine.
Dong, TS, Jacobs, JP, Hussain, SK
Current gastroenterology reports. 2019;(10):50
-
-
Free full text
-
Abstract
PURPOSE OF REVIEW The aim of this review is to summarize the recent literature on associations of small intestinal microbial and bile acid profiles with liver cirrhosis and its complications. RECENT FINDINGS Recent studies into the duodenal microbiome of patients with cirrhosis have linked the microbiome to certain etiologies of chronic liver disease as well as complications of cirrhosis. In particular, microbial differences in the duodenum of patients with cirrhosis have been linked to the presence of hepatic encephalopathy and varices. While the fecal microbiome of patients with liver cirrhosis is well characterized, the small intestinal microbiome of cirrhotic patients is an active area of research. This review focuses on the current understanding of the small intestinal microbiome in human cirrhosis as well as future directions of the field.
-
6.
Performance measures for small-bowel endoscopy: A European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative.
Spada, C, McNamara, D, Despott, EJ, Adler, S, Cash, BD, Fernández-Urién, I, Ivekovic, H, Keuchel, M, McAlindon, M, Saurin, JC, et al
United European gastroenterology journal. 2019;(5):614-641
-
-
Free full text
-
Abstract
The European Society of Gastrointestinal Endoscopy (ESGE) together with the United European Gastroenterology (UEG) recently developed a short list of performance measures for small-bowel endoscopy (i.e. small-bowel capsule endoscopy and device-assisted enteroscopy) with the final goal of providing endoscopy services across Europe with a tool for quality improvement. Six key performance measures both for small-bowel capsule endoscopy and for device-assisted enteroscopy were selected for inclusion, with the intention being that practice at both a service and endoscopist level should be evaluated against them. Other performance measures were considered to be less relevant, based on an assessment of their overall importance, scientific acceptability, and feasibility. Unlike lower and upper gastrointestinal endoscopy, for which performance measures had already been identified, this is the first time small-bowel endoscopy quality measures have been proposed.
-
7.
Primary neoplasms of the small bowel at CT: a pictorial essay for the clinician.
Minordi, LM, Binda, C, Scaldaferri, F, Holleran, G, Larosa, L, Belmonte, G, Gasbarrini, A, Colosimo, C, Manfredi, R
European review for medical and pharmacological sciences. 2018;(3):598-608
Abstract
OBJECTIVE Primary small intestinal neoplasms are uncommon tumors that are often small and difficult to identify. The aim of this paper is to describe CT technique and features in detecting and characterizing the tumors of the small bowel. MATERIALS AND METHODS This paper focuses on radiological characteristics of benign and malignant primary neoplasms of the small bowel at CT, with special reference to multidetector-CT techniques, type and modality of administration of contrast agents (by oral route or CT-enterography and by nasojejunal tube or CT-enteroclysis). This paper will also provide pictures and description of CT findings of benign and malignant primary neoplasms using examples of CT-enterography and CT-enteroclysis. RESULTS Among CT modalities, CT-enterography has the advantage of defining the real extension of wall lesions, possible transmural extension, the degree of mesenteric involvement and remote metastasis. Other useful modalities for the diagnosis of such lesions like capsule endoscopy and enteroscopy, provide important information but limited to mucosal changes with lower accuracy on extension and bowel wall involvement or submucosal lesions. CONCLUSIONS Multidetector-CT, performed after distension of the small bowel with oral contrast material and intravenous injection of iodinated contrast material, is a useful method for the diagnosis and staging of small bowel neoplasms.
-
8.
Exploring the relationship between environmental enteric dysfunction and oral vaccine responses.
Church, JA, Parker, EP, Kosek, MN, Kang, G, Grassly, NC, Kelly, P, Prendergast, AJ
Future microbiology. 2018;(9):1055-1070
Abstract
Oral vaccines significantly underperform in low-income countries. One possible contributory factor is environmental enteric dysfunction (EED), a subclinical disorder of small intestinal structure and function among children living in poverty. Here, we review studies describing oral vaccine responses and EED. We identified eight studies evaluating EED and oral vaccine responses. There was substantial heterogeneity in study design and few consistent trends emerged. Four studies reported a negative association between EED and oral vaccine responses; two showed no significant association; and two described a positive correlation. Current evidence is therefore insufficient to determine whether EED contributes to oral vaccine underperformance. We identify roadblocks in the field and future research needs, including carefully designed studies those can investigate this hypothesis further.
-
9.
Celiac Disease and Glandular Autoimmunity.
Kahaly, GJ, Frommer, L, Schuppan, D
Nutrients. 2018;(7)
Abstract
Celiac disease is a small intestinal inflammatory disease with autoimmune features that is triggered and maintained by the ingestion of the storage proteins (gluten) of wheat, barley, and rye. Prevalence of celiac disease is increased in patients with mono- and/or polyglandular autoimmunity and their relatives. We have reviewed the current and pertinent literature that addresses the close association between celiac disease and endocrine autoimmunity. The close relationship between celiac disease and glandular autoimmunity can be largely explained by sharing of a common genetic background. Further, between 10 and 30% of patients with celiac disease are thyroid and/or type 1 diabetes antibody positive, while around 5⁻7% of patients with autoimmune thyroid disease, type 1 diabetes, and/or polyglandular autoimmunity are IgA anti-tissue transglutaminase antibody positive. While a gluten free diet does not reverse glandular autoimmunity, its early institution may delay or even prevent its first manifestation. In conclusion, this brief review highlighting the close association between celiac disease and both monoglandular and polyglandular autoimmunity, aims to underline the need for prospective studies to establish whether an early diagnosis of celiac disease and a prompt gluten-free diet may positively impact the evolution and manifestation of glandular autoimmunity.
-
10.
Small intestinal bacterial overgrowth as a cause for irritable bowel syndrome: guilty or not guilty?
Aziz, I, Törnblom, H, Simrén, M
Current opinion in gastroenterology. 2017;(3):196-202
-
-
Free full text
-
Abstract
PURPOSE OF REVIEW Small intestinal bacterial overgrowth (SIBO) has been proposed as a cause of irritable bowel syndrome (IBS). However, this relationship has been subject to controversy. This review aims to provide a current perspective on the SIBO-IBS hypothesis. RECENT FINDINGS Case-control studies evaluating the prevalence of SIBO in IBS and healthy individuals have shown conflicting results. Moreover, the tests available in routine clinical practice to diagnose SIBO are not valid and lack both sensitivity and specificity. Hence, interpreting the effect of interventions based on these tests is fraught with uncertainty. Furthermore, the SIBO-IBS hypothesis has paved the way to assess antibiotic therapy in nonconstipated IBS, with rifaximin, a nonabsorbable antibiotic, showing modest but significant clinical benefit. However, individuals were not tested for SIBO and the mechanism of action of rifaximin in IBS remains to be elucidated. Preliminary data suggest that rifaximin decreases microbial richness and previous studies have noted antibacterial interventions in IBS to reduce colonic fermentation and improve symptoms. The advent of rapid culture-independent molecular techniques is a promising tool that will seek to clarify and advance our understanding of the gut microbial function. SUMMARY The SIBO-IBS hypothesis lacks convincing evidence but remains under scrutiny. The mechanism resulting in symptom improvement after rifaximin treatment in some IBS individuals requires exploration. Novel molecular techniques provide an exciting and challenging opportunity to explore the host-gut microbiota interaction.