Herbal medicines for the treatment of functional and inflammatory bowel disorders

In many parts of the world, there continues to be a long-standing tradition of prescribing herbal products for a range of gastrointestinal conditions. Scientific evidence supporting the use of all herbal preparations is imperfect, however, and available studies are plagued by methodological limitations. For functional gastrointestinal disorders, there is limited evidence supporting the use of some well-characterized preparations. A number of herbals have immunomodulatory activity, and in inflammatory bowel disease there are limited positive placebo-controlled trials; other studies used active controls with suboptimal doses of the comparators. Like all drugs, herbals can lead to serious adverse events (eg, hepatic failure). Quality control is a serious issue to consider when prescribing herbal medicines. Many herbal preparations are marketed without evidence for stringent adherence to good manufacturing practice guidelines. Unpredictable environmental conditions may affect the composition and the concentration of the active ingredients of plant extracts. Further, commercial herbal products usually combine a variable plethora of chemical families with possible medicinal utility. While some of these ingredients might be of benefit, the concentration and dose of these constituents needs to be closely monitored. Physicians and regulators need to remain very cautious about the use of herbal remedies. Appropriate scientific evidence for the claimed clinical benefits should become mandatory worldwide, and the standards for production and safety monitoring should comply with established standards for chemically defined products. If these principles were adopted, the full value of herbal remedies may come to light, particularly as the individually bioactive compounds present in these preparations become recognized

An Adaptive Treatment Strategy for Oral Vancomycin in Patients with the Orphan Disease Primary Sclerosing Cholangitis.

Decision-making in clinical medicine ideally is based upon evidence from randomized, placebo-controlled trials (RCTs) and subsequent systematic reviews and meta-analyses. However, for orphan diseases, the expectation of having one or multiple RCTs that inform clinical guidelines or justify specific treatments can be unrealistic and subsequent therapeutic nihilism can be detrimental to patients. This article discusses the benefits of therapeutic decision-making in the context of orphan diseases, focusing on primary sclerosing cholangitis (PSC) as an example of an orphan disease with poor clinical outcomes. PSC is a rare disorder characterized by inflammation and progressive fibrosis of the bile ducts. It carries a high risk of liver failure, malignancies, and debilitating symptoms that impair quality of life. Liver transplantation is currently the only life-prolonging intervention for PSC, but it is not a curative option. The article highlights the potential benefits of treating PSC patients with oral vancomycin (OV), which has shown significant clinical responses and improved quality of life in some cases. However, access to OV therapy is limited due to the lack of RCTs supporting its use. The standard requirement of having evidence from RCTs may result in withholding potentially life-altering and/or life-saving treatments for patients with orphan diseases. Conducting RCTs is challenging in these patient populations due to difficulties in recruiting the required patient cohorts and limited commercial returns. A standardized adaptive treatment strategy is proposed to address this. This approach leverages the best available evidence for specific treatments, considers individual clinical responses, and adjusts treatment over time

ScenarioTools Real-Time Play-Out for Test Sequence Validation in an Automotive Case Study

In many areas, such as automotive, healthcare, or production, we find software-intensive systems with complex real-time requirements. To efficiently ensure the quality of these systems, engineers require automated tools for the validation of the requirements throughout the development. This, however, requires that the requirements are specified in an analyzable way. We propose modeling the specification using Modal Sequence Diagrams (MSDs), which express what a system may, must, or must not do in certain situations. MSDs can be executed via the play-out algorithm to investigate the behavior emerging from the interplay of multiple scenarios; we can also test if traces of the final product satisfy all scenarios. In this paper, we present the first tool supporting the play-out of MSDs with real-time constraints. As a case study, we modeled the requirements on gear shifts in an upcoming standard on vehicle testing and use our tool to validate externally generated gear shift sequences

Calculations of Adsorption-Dependent Refractive Indices of Metal-Organic Frameworks for Gas Sensing Applications

Detection of Volatile Organic Compounds (VOCs) is One of the Most Challenging Tasks in Modelling Breath Analyzers Because of their Low Concentrations (Parts-Per-Billion (Ppb) to Parts-Per-Million (Ppm)) in Breath and the High Humidity Levels in Exhaled Breaths. the Refractive Index is One of the Crucial Optical Properties of Metal-Organic Frameworks (MOFs), Which is Changeable Via the Variation of Gas Species and Concentrations that Can Be Utilized as Gas Detectors. Herein, for the First Time, We Used Lorentz–Lorentz, Maxwell–Ga, and Bruggeman Effective Medium Approximation (EMA) Equations to Compute the Percentage Change in the Index of Refraction (∆n%) of ZIF-7, ZIF-8, ZIF-90, MIL-101(Cr) and HKUST-1 Upon Exposure to Ethanol at Various Partial Pressures. We Also Determined the Enhancement Factors of the Mentioned MOFs to Assess the Storage Capability of MOFs and the Biosensors\u27 Selectivity through Guest-Host Interactions, Especially, at Low Guest Concentrations

Antidepressants and inflammatory bowel disease: a systematic review

BACKGROUND: A number of studies have suggested a link between the patient's psyche and the course of inflammatory bowel disease (IBD). Although pharmacotherapy with antidepressants has not been widely explored, some investigators have proposed that treating psychological co-morbidities with antidepressants may help to control disease activity. To date a systematic analysis of the available studies assessing the efficacy of antidepressants for the control of somatic symptoms in IBD patients has not been performed. METHODS: We searched electronic databases, without any language restriction. All relevant papers issued after 1990 were examined. RESULTS: 12 relevant publications were identified. All of them referred to non-randomised studies. Antidepressants reported in these publications included paroxetine, bupropion, amitriptyline, phenelzine, and mirtazapine. In 10 articles, paroxetine, bupropion, and phenelzine were suggested to be effective for treating both psychological and somatic symptoms in patients suffering from IBD. Amitriptyline was found ineffective for treating somatic symptoms of IBD. Mirtazapine was not recommended for IBD patients. CONCLUSION: Although most of reviewed papers suggest a beneficial effect of treatment with antidepressants in patients with IBD, due to the lack of reliable data, it is impossible to judge the efficacy of antidepressants in IBD. Properly designed trials are justified and needed based upon the available uncontrolled data

Dietary fiber intervention on gut microbiota composition in healthy adults:a systematic review and meta-analysis

BackgroundDysfunction of the gut microbiota is frequently reported as a manifestation of chronic diseases, and therefore presents as a modifiable risk factor in their development. Diet is a major regulator of the gut microbiota, and certain types of dietary fiber may modify bacterial numbers and metabolism, including short-chain fatty acid (SCFA) generation.ObjectiveA systematic review and meta-analysis were undertaken to assess the effect of dietary fiber interventions on gut microbiota composition in healthy adults.DesignA systematic search was conducted across MEDLINE, EMBASE, CENTRAL, and CINAHL for randomized controlled trials using culture and/or molecular microbiological techniques evaluating the effect of fiber intervention on gut microbiota composition in healthy adults. Meta-analyses via a random-effects model were performed on alpha diversity, prespecified bacterial abundances including Bifidobacterium and Lactobacillus spp., and fecal SCFA concentrations comparing dietary fiber interventions with placebo/low-fiber comparators.ResultsA total of 64 studies involving 2099 participants were included. Dietary fiber intervention resulted in higher abundance of Bifidobacterium spp. (standardized mean difference (SMD): 0.64; 95% CI: 0.42, 0.86; P < 0.00001) and Lactobacillus spp. (SMD: 0.22; 0.03, 0.41; P = 0.02) as well as fecal butyrate concentration (SMD: 0.24; 0.00, 0.47; P = 0.05) compared with placebo/low-fiber comparators. Subgroup analysis revealed that fructans and galacto-oligosaccharides led to significantly greater abundance of both Bifidobacterium spp. and Lactobacillus spp. compared with comparators (P < 0.00001 and P = 0.002, respectively). No differences in effect were found between fiber intervention and comparators for α-diversity, abundances of other prespecified bacteria, or other SCFA concentrations.ConclusionsDietary fiber intervention, particularly involving fructans and galacto-oligosaccharides, leads to higher fecal abundance of Bifidobacterium and Lactobacillus spp. but does not affect α-diversity. Further research is required to better understand the role of individual fiber types on the growth of microbes and the overall gut microbial community. This review was registered at PROSPERO as CRD42016053101

Miniature Optical Fiber Fabry-Perot Interferometer Based On A Single-Crystal Metal-Organic Framework For The Detection And Quantification Of Benzene And Ethanol At Low Concentrations In Nitrogen Gas

This study reports for the first time, to the best of our knowledge, a real-time detection of ultralow-concentration chemical gases using fiber-optic technology, combining a miniaturized Fabry-Perot interferometer (FPI) with metal-organic frameworks (MOFs). The sensor consists of a short and thick-walled silica capillary segment spliced to a lead-in single-mode fiber (SMF), housing a tiny single crystal of HKUST-1 MOF, imparting chemo selectivity features. Ethanol and benzene gases were tested, resulting in a shift in the FPI interference signal. The sensor demonstrated high sensitivity, detecting ethanol gas concentrations (EGCs) with a sensitivity of 0.428 nm/ppm between 24.9 and 40.11 ppm and benzene gas concentrations (BGCs) with a sensitivity of 0.15 nm/ppm between 99 and 124 ppm. The selectivity study involved a combination of three ultralow concentrations of ethanol, benzene, and toluene gases, revealing an enhancement factor of 436% for benzene and 140% for toluene, attributed to the improved miscibility of these conjugated ring molecules with the alkane chains of the ethanol-modified HKUST-1. Experimental tests confirmed the sensor\u27s viability, demonstrating significantly improved response time and spectral characteristics through crystal polishing, indicating its potential for quantifying and detecting chemical gases at ultralow concentrations. This technology may prevent energy resource losses, and the sensor\u27s small size and robust construction make it applicable in confined and hazardous locations

The biogeography of the mucosa-associated microbiome in health and disease

IntroductionLittle is known about the biogeography of the mucosa associated microbiome (MAM) in patients with inflammatory bowel disease (IBD) versus controls in different segments of the gastrointestinal tract, as well as the links between the MAM, gastrointestinal symptoms, and use of proton pump inhibitors (PPI).MethodsWe recruited 59 controls (without structural abnormalities and gastrointestinal symptoms), 44 patients with ulcerative colitis (UC) and 31 with Crohn’s disease (CD). Biopsies from various segments of the upper and lower gastrointestinal tract were collected. Microbial composition was assessed via 16S rRNA gene amplicon analysis and the bacterial load of the mucosal biopsies were assessed via qPCR. The MAM was examined in the context of disease status, PPI usage, the severity of gastrointestinal symptoms, and the symptom response to a standardised nutrient challenge (SNC).ResultsMicrobial communities of the MAM in the upper and lower gastrointestinal tract differed. IBD patients were characterised by relative and absolute depletion of numerous genera known to produce butyrate and/or propionate, with the largest differentiation being the depletion of Faecalibacterium in the lower gastrointestinal tract of CD patients. Notably, PPI users exhibited an enrichment of Faecalibacterium in the lower gastrointestinal tract. The severity of gastrointestinal symptoms, as well as the symptom response to the SNC, were significantly associated with MAM composition in the gastrointestinal tract.ConclusionThe absolute and relative composition of the MAM is variable across different segments of the gastrointestinal tract. These quantitative changes indicates that MAM can be targeted in specific segments of the GI tract to improve patient outcomes

A placebo-controlled trial of itopride in functional dyspepsia

Dyspepsia remains a common and costly problem in primary care and gastroenterology practice; in most patients who are examined, no structural lesions causing these symptoms are found.1 Dyspepsia in the absence of a clinically identifiable structural lesion is referred to as functional dyspepsia,2,3 in part because disturbed gastrointestinal function is believed to play a role in the development of symptoms.4 Pharmacologic treatments for patients with functional dyspepsia remain unsatisfactory.5 The results of controlled trials have generally been disappointing, and only small benefits relative to placebo have been found with histamine H 2 -receptor antagonists,6 proton-pump inhibitors,7 and Helicobacter pylori eradication.8 Although several randomized, controlled trials and metaanalyses have demonstrated the superiority of cisapride over placebo,9-11 the use of cisapride is now restricted in most countries because of cardiac side effects. In Japan, itopride, which is a dopamine D2 antagonist with acetylcholinesterase inhibitory actions, is often prescribed for patients with functional dyspepsia. Although this drug has been shown to stimulate gastric motility,12 large, properly designed, randomized, controlled trials in patients with functional dyspepsia are lacking. In Japan, administration of 50 mg three times daily is standard practice. However, little is known regarding the dose response in other populations. For this reason, we aimed to study the efficacy of itopride in patients with functional dyspepsia in terms of symptom improvement and to compare various doses of itopride in terms of efficacy and safety in a white population. Methods Study Design and Patient Population Patients Outpatients who were considered to have functional dyspepsia on the basis of the Rome II criteria3 were eligible for the trial. Functional dyspepsia was diagnosed if persistent or recurrent upper abdominal pain or discomfort was present. Discomfort was characterized by the presence of one or more symptoms that included early satiety, postprandial fullness, bloating, and nausea