Quality of life in patients with functional dyspepsia: Short- and long-term effect of Helicobacter pylori eradication with pantoprazole, amoxicillin, and clarithromycin or cisapride therapy: A prospective, parallel-group study

AbstractBackground:Quality of life (QOL) is impaired in functional dyspepsia (FD). Little is known about the effects of different therapies on the QOL profile in patients with this condition.Objectives:The aims of this study were to measure baseline QOL in patients with FD and to assess changes in QOL over time associated with Helicobacter pylori eradication and prokinetic treatment. The primary and secondary end points were the improvement in QOL 6 weeks and 1 year after successful eradication of the infection or prokinetic therapy.Methods:This 1-year, single-center, prospective, open-label, controlled, parallel-group trial was conducted at the Department of Gastroenterology, Ferencvdros Health Centre, Budapest, Hungary. The Functional Digestive Disorder Quality of Life (FDDQoL) Questionnaire (MAPI Research Institute, Lyon, France) was translated and validated previously in Hungarian. Male and female subjects aged 20 to 60 years were enrolled and classified as H pylori positive (HP+), H pylori negative (HP-) with FD, or healthy (control group). The HP+ patients received pantoprazole 40 mg BID + amoxicillin 1000 mg BID + clarithromycin 500 mg BID for 7 days, followed by on-demand ranitidine (150–300 mg/d) for 1 year. The HP- patients received the prokinetic cisapride 10 mg TID for 1 month, followed by on-demand cisapride (10–20 mg/d) for 1 year. The FDDQoL questionnaire was completed by all 3 groups on enrollment, at 6 weeks, and 1 year.Results:A total of 101 HP+ patients, 98 HP- patients, and 123 healthy controls were included in the study (185 women, 137 men; mean age, 39.0 ears). The mean (SD) baseline QOL scores were significantly lower in the HP+ group (53.3 [9.6]; 95% CI, 54.4-58.2) and the HP- groups (50.0 [9.8]; 95% CI, 58.0–62.0) compared with that in healthy controls (76.2 [8.7]; 95% CI, 74.6–77.8) (both, P < 0.001). Analysis of the short-term domain scores found that the HP+ group had significantly decreased scores in 6 of 8 domains: daily activities (P = 0.005), anxiety level (P = 0.02), diet (P = 0.008), sleep (P < 0.001), discomfort (P = 0.004), and disease control (P = 0.02); the HP- group had significantly decreased scores in 5 of 8 domains: daily activities (P < 0.001), diet (P = 0.004), sleep (P = 0.005), discomfort (P < 0.001), and disease control (P = 0.02). Eradication of the infection was successful in 77/101 (76.2%) of the patients on intent-to-treat analysis and 77/94 (81.9%) on per-protocol analysis. Eradication was associated with an increase in mean (SD) QOL score to 70.8 (10.7) at 6 weeks (95% CI, 63.3–73.2; P < 0.001 vs baseline) and to 75.3 (9.3) at 1 year (95% CI, 73.2–77.5; P= 0.05 vs 6 weeks). In the HP- group, the QOL score increased to 73.3 (9.7) (95% CI, 71.3–75.4; P < 0.001 vs baseline) at 6 weeks of cisapride treatment and to 76.5 (8.5) at 1 year (95% CI, 74.5–78.4; P = 0.06 vs 6 weeks). Most of the impaired domain scores improved significantly after both treatments. The short-term effect size was 1.48 in HP+ and 1.35 in HP− patients. Adverse events (AEs) occurred in 22 (21.8%) patients in the HP+ group (nausea, 8 [7.9%] patients; diarrhea, 5 [5.0%]; loss of appetite, 5 [5.0%]; stomatitis, 5 [5.0%]; abdominal pain, 4 [4.0%]; bloating, 4 [4.0%]; headache, 4 [4.0%]; vomiting, 4 [4.0%]; constipation, 3 [3.0%]; and vaginitis, 3 [3.0%]). In HP− cases, AEs occurred in 9 (9.2%) patients (abdominal cramps, 7 [7.1%]; diarrhea, 4 [4.1%]; and nausea, 3 [3.1%]).Conclusion:In this study in patients with FD and healthy controls, eradication of H pylori infection in infected patients and cisapride treatment in uninfected patients reversed low QOL scores during the 1-year follow-up period

Improved Characterization of EV Preparations Based on Protein to Lipid Ratio and Lipid Properties.

In recent years the study of extracellular vesicles has gathered much scientific and clinical interest. As the field is expanding, it is becoming clear that better methods for characterization and quantification of extracellular vesicles as well as better standards to compare studies are warranted. The goal of the present work was to find improved parameters to characterize extracellular vesicle preparations. Here we introduce a simple 96 well plate-based total lipid assay for determination of lipid content and protein to lipid ratios of extracellular vesicle preparations from various myeloid and lymphoid cell lines as well as blood plasma. These preparations included apoptotic bodies, microvesicles/microparticles, and exosomes isolated by size-based fractionation. We also investigated lipid bilayer order of extracellular vesicle subpopulations using Di-4-ANEPPDHQ lipid probe, and lipid composition using affinity reagents to clustered cholesterol (monoclonal anti-cholesterol antibody) and ganglioside GM1 (cholera toxin subunit B). We have consistently found different protein to lipid ratios characteristic for the investigated extracellular vesicle subpopulations which were substantially altered in the case of vesicular damage or protein contamination. Spectral ratiometric imaging and flow cytometric analysis also revealed marked differences between the various vesicle populations in their lipid order and their clustered membrane cholesterol and GM1 content. Our study introduces for the first time a simple and readily available lipid assay to complement the widely used protein assays in order to better characterize extracellular vesicle preparations. Besides differentiating extracellular vesicle subpopulations, the novel parameters introduced in this work (protein to lipid ratio, lipid bilayer order, and lipid composition), may prove useful for quality control of extracellular vesicle related basic and clinical studies

Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles

Release of membrane vesicles, a process conserved in both prokaryotes and eukaryotes, represents an evolutionary link, and suggests essential functions of a dynamic extracellular vesicular compartment (including exosomes, microparticles or microvesicles and apoptotic bodies). Compelling evidence supports the significance of this compartment in a broad range of physiological and pathological processes. However, classification of membrane vesicles, protocols of their isolation and detection, molecular details of vesicular release, clearance and biological functions are still under intense investigation. Here, we give a comprehensive overview of extracellular vesicles. After discussing the technical pitfalls and potential artifacts of the rapidly emerging field, we compare results from meta-analyses of published proteomic studies on membrane vesicles. We also summarize clinical implications of membrane vesicles. Lessons from this compartment challenge current paradigms concerning the mechanisms of intercellular communication and immune regulation. Furthermore, its clinical implementation may open new perspectives in translational medicine both in diagnostics and therapy

Molecular interactions at the surface of extracellular vesicles

Extracellular vesicles such as exosomes, microvesicles, apoptotic bodies, and large oncosomes have been shown to participate in a wide variety of biological processes and are currently under intense investigation in many different fields of biomedicine. One of the key features of extracellular vesicles is that they have relatively large surface compared to their volume. Some extracellular vesicle surface molecules are shared with those of the plasma membrane of the releasing cell, while other molecules are characteristic for extracellular vesicular surfaces. Besides proteins, lipids, glycans, and nucleic acids are also players of extracellular vesicle surface interactions. Being secreted and present in high number in biological samples, collectively extracellular vesicles represent a uniquely large interactive surface area which can establish contacts both with cells and with molecules in the extracellular microenvironment. Here, we provide a brief overview of known components of the extracellular vesicle surface interactome and highlight some already established roles of the extracellular vesicle surface interactions in different biological processes in health and disease

The history and rationale of using carbonic anhydrase inhibitors in the treatment of peptic ulcers. In memoriam Ioan Puşcaş (1932–2015)

<p>Carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) started to be used in the treatment of peptic ulcers in the 1970s, and for more than two decades, a group led by <i>Ioan Puşcaş</i> used them for this purpose, assuming that by inhibiting the gastric mucosa CA isoforms, hydrochloric acid secretion is decreased. Although acetazolamide and other sulfonamide CAIs are indeed effective in healing ulcers, the inhibition of CA isoforms in other organs than the stomach led to a number of serious side effects which made this treatment obsolete when the histamine H2 receptor antagonists and the proton pump inhibitors became available. Decades later, in 2002, it has been discovered that <i>Helicobacter pylori</i>, the bacterial pathogen responsible for gastric ulcers and cancers, encodes for two CAs, one belonging to the α-class and the other one to the β-class of these enzymes. These enzymes are crucial for the life cycle of the bacterium and its acclimation within the highly acidic environment of the stomach. Inhibition of the two bacterial CAs with sulfonamides such as acetazolamide, a low-nanomolar <i>H. pylori</i> CAI, is lethal for the pathogen, which explains why these compounds were clinically efficient as anti-ulcer drugs. Thus, the approach promoted by <i>Ioan Puşcaş</i> for treating this disease was a good one although the rationale behind it was wrong. In this review, we present a historical overview of the sulfonamide CAIs as anti-ulcer agents, in memoriam of the scientist who was in the first line of this research trend.</p