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Background: There is no single gold standard for investigation of gastrointestinal motility function. Wireless motility monitoring involves a novel concept which provides a complex information on gastrointestinal function (gastrointestinal transit time, intra-luminal pH, pressure and temperature). Gastrointestinal motility functions of experimental pigs are very similar to those of humans. That is why porcine studies have already provided suitable experimental models for several preclinical projects. Aims: The aim of our study was to adopt methods of non-invasive wireless monitoring of gastrointestinal functions in experimental pigs. Methods: Five experimental adult female pigs were enrolled into the study. Wireless motility capsules were delivered into the porcine stomach endoscopically. Gastrointestinal transit and intra-luminal conditions were recorded for five days. Results: Records of animals provided good (3 pigs) or very good quality files (2 pigs). 31150 variables were evaluated. Mean time of the presence of capsules in the stomach was 926 ± 295 min, transfer of a capsule from the stomach into the duodenum lasted 5–34 min. Mean small intestinal transit time was 251 ± 43 min. Food intake was associated with an increase of gastric luminal temperature and a decrease of intra-gastric pressure. The highest intra-luminal pH was present in the ileum. The highest temperature and the lowest intra-luminal pressure were found in the colon. All data displayed a substantial inter-individual variability. Conclusions: This pilot study has proven that a long-term function monitoring of the gastrointestinal tract by means of wireless motility capsules in experimental pigs is feasible. However, both ketamine-based induction of general anaesthesia as well as long-lasting general anaesthesia (> 6 hours) should be avoided to prevent retention of a capsule in the porcine stomach.

Introduction: To date, there is not generally accepted and universal indicator of activity, and functional integrity of the small intestine in patients with coeliac disease. The aim of our study was to investigate whether serum concentrations of the non-essential amino acids citrulline and ornithine might have this function. Methods: We examined serum citrulline and ornithine concentrations in a subgroup of patients with proven coeliac disease and healthy controls (blood donors). Results: A total of 94 patients with coeliac disease (29 men, mean age 53 ± 18 years; 65 women, mean age 44 ± 14 years) and 35 healthy controls (blood donors) in whom coeliac disease was serologically excluded (10 men, mean age 51 ± 14 years; 25 women, mean age 46 ± 12 years) were included in the study. Significantly lower concentrations of serum ornithine were found in patients with coeliac disease (mean 65 ± 3 μmol/L; median 63 μmol/L, IQR 34 μmol/L, p < 0.001). No statistically nor clinically significant differences were found in the citrulline concentrations between the study and control group. Conclusions: Serum ornithine (but not citrulline) may be useful for assessing the functional status of the small intestine in uncomplicated coeliac disease. Further studies involving more detailed analysis of dietary and metabolic changes in patients will be needed to reach definitive conclusions.

BUREŠ, Jan. The Presidium of the Central Committee of the Communist Party of Czechoslovakia in the period of the post-war construction of the party up to the parlamentary election in 1946. Historický časopis, 2022, 70, 2, pp. 271-303, Bratislava. In this study we deal mainly with the role of the central bodies of the leadership of the Communist Party of Czechoslovakia, namely the Bureau of the Central Committee and its Secretariat, in the period from the liberation of Czechoslovakia in May 1945 to the parliamentary elections in May 1946. The presidency of the Communist Party was the highest level of a branched network of party organizations, for which it issued basic political lines and general instructions, which were subsequently developed by the Secretariat of the Central Committee of the Communist Party. Both of these organs were relatively small, and after the first phase of their formation after the war, they quickly stabilized in terms of personnel. The Communist Party continued to be governed strongly autocratically after the war. All power was concentrated in their hands by a narrow circle of members of the Presidium of the Central Committee of the party with the dominant position of Chairman Gottwald, whose decisions were implemented by the Secretariat, autocratically controlled by R. Slánský. In the period under review, both bodies focused mainly on key issues of political development and the resulting party strategy. It was mainly about solving the organizational construction of the party, the mass influx of new members, key issues of propaganda and influencing the media, solving the complicated Slovak issue, the establishment of the Provisional National Assembly in 1945, and the preparation and conduct of VIII. Congress of the Communist Party and the election campaign.

IntroductionPathogenic strains of Escherichia coli have been clearly identified as the causative agents of extraintestinal and diarrheal infections; however, the etiopathogenic role of E. coli in other conditions, including colorectal cancer, remains unclear.MethodsThis study aimed to characterize mucosal E. coli isolates (n = 246) from 61 neoplasia patients and 20 healthy controls for the presence of 35 genetic determinants encoding known virulence factors.ResultsVirulence determinants encoding invasin (ibeA), siderophore receptor (iroN), S-fimbriae (sfa), and genotoxin (usp) were more prevalent among E. coli isolated from patients with neoplasia compared to the control group (p < 0.05). In addition, the prevalence of these virulence determinants was increased in more advanced neoplasia stages (padj < 0.0125). Compared to patients with advanced colorectal adenoma and carcinoma, the ibeA gene was rarely found in the control group and among patients with non-advanced adenoma (p < 0.05), indicating its potential as the advanced-neoplasia biomarker. Patients with neoplasia frequently had E. coli strains with at least one of the abovementioned virulence factors, whereby specific combinations of these virulence factors were found.DiscussionThese findings suggest that E. coli strains isolated from patients with colorectal neoplasia possess several virulence factors, which could contribute to the development of neoplastic processes in the large intestine.

Introduction: The inflammatory process in Crohn’s disease (CD) is closely associated with the formation of reactive oxygen species. Antioxidant enzymes can play an important role in the outcome of CD and may influence postoperative recurrence in these patients. The aim of our study was to evaluate gene expression of intracellular antioxidant enzymes in surgically resected intestinal specimens of patients with CD, both in macroscopically normal and in inflamed tissue. Methods: A total of 28 patients referred for elective bowel resection were enrolled in the study. Full-thickness small intestinal specimens were investigated. Gene expression of antioxidant enzymes – superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GSR) – was evaluated both in macroscopically normal and inflamed samples. Results: There were significantly lower levels of SOD1 mRNA (p = 0.007) and GSR mRNA (p = 0.027) in inflamed tissue compared to macroscopically normal areas. No significant differences were found between affected and non-affected intestinal segments in mRNA for SOD2, SOD3 and GPX. Conclusions: Our pilot data clearly showed that the gene expression of major antioxidant enzymes is not a uniform mechanism in the pathogenesis of Crohn’s disease. Topically decreased gene expression of SOD1 and GSR might facilitate the segmental tissue injury caused by reactive oxygen species.

Background: Gastrointestinal injury caused by dextran sodium sulphate (DSS) is a reliable porcine experimental model of inflammatory bowel disease (IBD). The purpose of this study was to evaluate the effect of probiotic Lactobacillus casei DN 114001 (LC) on DSS-induced experimental IBD.Results: Eighteen female pigs (Sus scrofa f. domestica, weight 33–36 kg, age 4–5 months) were divided into 3 groups (6 animals per group): controls with no treatment, DSS, and DSS + LC. LC was administered to overnight fasting animals in a dietary bolus in the morning on days 1–7 (4.5 × 1010 live bacteria/day). DSS was applied simultaneously on days 3–7 (0.25 g/kg/day). On day 8, the pigs were sacrificed. Histopathological score and length of crypts/glands (stomach, jejunum, ileum, transverse colon), length and width of villi (jejunum, ileum), and mitotic and apoptotic indices (jejunum, ileum, transverse colon) were assessed. DSS increased the length of glands in the stomach, length of crypts and villi in the jejunum and ileum, and the histopathological score of gastrointestinal damage, length of crypts and mitotic activity in the transverse colon. Other changes did not achieve any statistical significance. Administration of LC reduced the length of villi in the jejunum and ileum to control levels and decreased the length of crypts in the jejunum. Conclusions: Treatment with a probiotic strain of LC significantly accelerated regeneration of the small intestine in a DSS-induced experimental porcine model of IBD.

A two-year-old girl with two weeks of abdominal pain, vomiting, and food refusal, ten months after percutaneous endoscopic gastrostomy insertion because of inadequate peroral intake, was admitted to a tertiary centre hospital. On admission, the extracorporeal part of the gastrostomy was much shortened. X-ray examination revealed migration of the end of the gastrostomy tube with a left-shifted course of the tube through the duodenum. Gastroscopy and subsequently laparotomy were performed. A longitudinal pressure necrosis was identified under the tube, with two perforations in the duodenojejunal region. Ten centimeters of that duodenojejunal region were resected, and end-to-end anastomosis was made. The migration of the gastrostomy was probably caused by insufficient care by the parents. Pathophysiologically, the tube caused the pressure necrosis in the duodenojejunal area; this was supported by histology. This is a hitherto undescribed complication of a percutaneous endoscopic gastrostomy, showing that migration of the gastrostomy to the deeper part of the small bowel can lead to pressure necrosis, a potentially life-threatening condition in children which cannot be treated without invasive procedures.

Pancreatic cancer is the seventh leading cause of cancer deaths worldwide and is associated with a poor survival rate. The vast majority of pancreatic cancers are inoperable at the time of diagnosis. In the absence of metastatic disease, operability depends on the extent of local disease; in particular, the presence or absence of vascular and lymph node involvement. Adequate staging is vital in deciding an appropriate treatment plan. Cross sectional imaging including CT, MRI and PET-CT are commonly used for staging. However, EUS is a useful adjunct for accurate loco-regional staging in addition to allowing diagnostic tissue samples to be obtained. Emerging EUS-guided therapeutic techniques have opened up new horizons in the management of pancreatic malignancy. EUS guidance can be used for coeliac plexus neurolysis in patients with intractable pain and fiducial placement in directing stereotactic radiotherapy. The majority of patients with cancer of the pancreatic head present with biliary obstruction. ERCP can be used to drain the obstructed biliary system with plastic or metal stents and offers an opportunity to confirm the diagnosis by obtaining brush cytology and forceps biopsy specimens. EUS-guided choledocho-duodenostomy or hepatico-gastrostomy is increasingly being employed for draining the biliary system if ERCP is unsuccessful.

Analysis of Exhaled breath condensate (EBC) is a re-discovered approach to monitoring the course of the disease and reduce invasive methods of patient investigation. However, the major disadvantage and shortcoming of the EBC is lack of reliable and reproducible standardization of the method. Despite many articles published on EBC, until now there is no clear consensus on whether the analysis of EBC can provide a clue to diagnosis of the diseases. The purpose of this paper is to investigate our own method, to search for possible standardization and to obtain our own initial experience. Thirty healthy volunteers provided the EBC, in which we monitored the density, pH, protein, chloride and urea concentration. Our results show that EBC pH is influenced by smoking, and urea concentrations are affected by the gender of subjects. Age of subjects does not play a role. The smallest coefficient of variation between individual volunteers is for density determination. Current limitations of EBC measurements are the low concentration of many biomarkers. Standardization needs to be specific for each individual biomarker, with focusing on optimal condensate collection. EBC analysis has a potential become diagnostic test, not only for lung diseases.

Introduction: The aim of our study was to assess association of serum S100A4 protein with ulcerative colitis (UC) and Crohn’s disease (CD). Methods: Study included 118 subjects: 93 patients with CD, 16 with UC and 9 controls. In CD group, 20/93 patients had B1 phenotype, 19/93 B2, 20/93 B3 and 34/93 B2 + B3. L1 involvement was present in 15/93, L2 in 14/93 and L3 in 64/93 patients. Serum S100A4 concentration was investigated in peripheral venous blood samples by means of ELISA. Results: Serum S100A4 was significantly higher in UC (158.6 ± 56.2 ng/mL), p = 0.019 and in CD (154.4 ± 52.1 ng/mL), p = 0.007 compared to controls (104.8 ± 40.5 ng/mL). No difference in S100A4 was revealed between UC and CD, p > 0.05. Serum S100A4 in each CD subgroup (according to behaviour) was significantly higher compared to controls, p < 0.05. Serum S100A4 was significantly higher in L2 (144.6 ± 44.2 ng/mL), p = 0.041 and in L3 (163.0 ± 52.8 ng/mL), p = 0.002 compared to controls and in L3 compared to L1 (126.9 ± 47.6 ng/mL), p = 0.017. Conclusion: Association of serum S100A4 protein with UC and CD was confirmed. In CD, disease behaviour did not influence serum concentration of S100A4 protein. In CD, higher levels of serum S100A4 were observed in patients with ileo-colonic and colonic involvement compared to those with isolated small bowel involvement.

Double balloon enteroscopy (DBE) was introduced 15 years ago. The complications of diagnostic DBE are rare, acute pancreatitis is most redoubtable one (incidence about 0.3%). Hyperamylasemia after DBE seems to be a rather common condition respectively. The most probable cause seems to be a mechanical straining of the pancreas. We tried to identify patients in a higher risk of acute pancreatitis after DBE. We investigated several laboratory markers before and after DBE (serum cathepsin B, lactoferrin, E-selectin, SPINK 1, procalcitonin, S100 proteins, alfa-1-antitrypsin, hs-CRP, malondialdehyde, serum and urine amylase and serum lipase). Serum amylase and lipase rose significantly with the maximum 4 hours after DBE. Serum cathepsin and procalcitonin decreased significantly 4 hours after DBE compared to healthy controls and patients values before DBE. Either serum amylase or lipase 4 hours after DBE did not correlate with any markers before DBE. There was a trend for an association between the number of push-and-pull cycles and procalcitonin and urine amylase 4 hours after DBE; between procalcitonin and alfa-1-antitrypsin, cathepsin and hs-CRP; and between E-selectin and malondialdehyde 4 hours after DBE. We found no laboratory markers determinative in advance those patients in a higher risk of acute pancreatitis after DBE.

Introduction: The aim of our prospective study was to define endoscopy appearance of the small bowel in healthy volunteers. Method: Forty-two healthy volunteers underwent wireless capsule endoscopy, clinical investigation, laboratory tests, and completed a health-status questionnaire. All subjects were available for a 36-month clinical follow-up. Results: Eleven subjects (26%) had fully normal endoscopy findings. Remaining 31 persons (74%), being asymptomatic, with normal laboratory results, had some minor findings at wireless capsule endoscopy. Most of those heterogeneous findings were detected in the small intestine (27/31; 87%), like erosions and/or multiple red spots, diminutive polyps and tiny vascular lesions. During a 36-month clinical follow-up, all these 42 healthy volunteers remained asymptomatic, with fully normal laboratory control. Conclusions: Significant part of healthy subjects had abnormal findings at wireless capsule endoscopy. These findings had no clinical relevance, as all these persons remained fully asymptomatic during a 36-month follow-up. Such an endoscopic appearance would be previously evaluated as “pathological”. This is a principal report alerting that all findings of any control group of wireless capsule endoscopic studies must be evaluated with caution.

Gastrointestinal lipomas are usually asymptomatic, detected incidentally. However, they can cause severe symptoms such as obstruction, invagination, and bleeding. The transsection of an infarcted or large lipoma by needle sphincterotome (needle knife) and/or snare polypectomy of the upper part of the tumour is an option for the endoscopy treatment of giant infarcted lipomas. Cutting a top of lipoma (unroofing technique) allowed flow out of adipose tissue from the lipoma.

The aim of this study project was to prepare our own method of porcine oesophageal manometry. Ten mature experimental pigs entered the study. Conventional water-perfused system was decided for manometry. Porcine resting and relaxed pressures of the lower oesophageal sphincter are fully comparable with healthy human subjects. Evocable swallowing is doable and oesophageal peristalsis is quantifiable. Basic manometric parameters were different in male and female animals. Oesophageal manometry in experimental pigs is feasible. Porcine oesophageal manometry will be usable for preclinical studies in future.

Bio-degradable stents are be made of different synthetic polymers (like polylactide or polyglycolide) or their co-polymers (polydioxanone). They can be used for treating benign stenoses of the small and large intestine, particularly in Crohn’s disease. Endoscopic introduction of bio-degradable stents into small and large intestinal stenoses is feasible and relatively simple. Initial results are encouraging and the complication rate is low. However, there are still some difficulties that need to be overcome. The rate of early stent migration is still rather high (up to one third of patients). This might be solved by changes in the shape or rigidity of the stents as well as by further improvement in the design. Proof of long-term efficacy and safety requires further studies.

Non-steroidal anti-inflammatory drug (NSAIDs) induced enteropathy represents an important complication of one of the most commonly used drugs worldwide. Due to previous diagnostics difficulties the real prevalence of this disease was underestimated for a long time. The pathogenesis of NSAID-enteropathy is more multifactorial and complex than formerly assumed but has still not been fully uncovered. A combination of the local and systemic effect plays an important role in pathogenesis. Thanks to novel enteroscopy methods (wireless capsule endoscopy, double balloon enteroscopy), small bowel lesions are described in a substantial section of NSAID users although most are clinically asymptomatic. The other non-invasive tests (small bowel permeability, faecal calprotectin, scintigraphy using faecal excretion of 111-indium-labelled leukocytes etc.) proposed for diagnostics are not generally used in clinical practice, mainly because of their non-specificity. Despite intensive research into possible treatment, the main measure for patients with NSAID-enteropathy is still withdrawal of NSAIDs. Double balloon enteroscopy plays an important role in the treatment of complications (bleeding, strictures).

Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare condition characterised by chronic or relapsing moderate ileous episodes resulting from multiple small intestinal strictures, multiple shallow ulcers of the small bowel and favourable therapeutical effect of glucocorticosteroids. The aim of this paper was to evaluate three cases of CMUSE diagnosed within 10 years at a tertiary gastroenterology centre. Three females (35, 50, 60 years) were presented with colicky pain, repeated moderate ileous episodes and weight loss. Multiple fibrous strictures and ulcers of the small bowel were found. All three patients responded to glucocorticosteroid treatment. Tandem tight jejunal stenoses were dilated endoscopically by means of double balloon enteroscopy. In conclusion, CMUSE should always be considered when chronic moderate ileous episodes and multiple small intestinal strictures and ulcers of uncertain aetiology are found. Double balloon enteroscopy enables precise diagnostic work, possible endoscopic treatment of stenoses, may obviate the need for surgery and prevent excessive small bowel resections.

Salicylaldehyde isonicotinoyl hydrazone (SIH) is a lipophilic, tridentate iron chelator with marked anti-oxidant and modest cytotoxic activity against neoplastic cells. However, it has poor stability in an aqueous environment due to the rapid hydrolysis of its hydrazone bond. In this study, we synthesized a series of new SIH analogs (based on previously described aromatic ketones with improved hydrolytic stability). Their structure-activity relationships were assessed with respect to their stability in plasma, iron chelation efficacy, redox effects and cytotoxic activity against MCF-7 breast adenocarcinoma cells. Furthermore, studies assessed the cytotoxicity of these chelators and their ability to afford protection against hydrogen peroxide-induced oxidative injury in H9c2 cardiomyoblasts. The ligands with a reduced hydrazone bond, or the presence of bulky alkyl substituents near the hydrazone bond, showed severely limited biological activity. The introduction of a bromine substituent increased ligand-induced cytotoxicity to both cancer cells and H9c2 cardiomyoblasts. A similar effect was observed when the phenolic ring was exchanged with pyridine (i.e., changing the ligating site from O, N, O to N, N, O), which led to pro-oxidative effects. In contrast, compounds with long, flexible alkyl chains adjacent to the hydrazone bond exhibited specific cytotoxic effects against MCF-7 breast adenocarcinoma cells and low toxicity against H9c2 cardiomyoblasts. Hence, this study highlights important structure-activity relationships and provides insight into the further development of aroylhydrazone iron chelators with more potent and selective anti-neoplastic effects.

Background. The purpose of study was to evaluate the diagnostic yield of capsule endoscopy for NSAID-induced enteropathy and clinical, laboratory, and endoscopic characteristics of disease in patients with rheumatoid arthritis. Methods. 37 rheumatoid arthritis patients (30 women; mean age 55) treated with NSAIDs (>1 month), presented with anaemia and/or positive faecal occult blood testing, entered the study and underwent capsule endoscopy (EndoCapsule; Olympus), laboratory tests, and filled in questionnaires. Results. The prevalence of NSAID-induced enteropathy diagnosed by capsule endoscopy was 68% (25/37), classified as mild (red spots or erosions) in 18 (49%), moderate (10–20 erosions) in 4 (11%), and severe enteropathy (>20 erosions or ulcers) in 3 (8%) patients. We did not find statistically significant relationship between the enteropathy and gender, age, haemoglobin, leukocytes, albumin and CRP, or dyspepsia. The difference between subgroups of NSAIDs according to the COX specificity was not statistically significant. Conclusions. Capsule endoscopy is a highly accurate noninvasive method for evaluation of NSAID-induced enteropathy. It was revealed in a substantial section of the patients with rheumatoid arthritis and occult gastrointestinal bleeding, mostly classified as mild damage. No simple clinical or laboratory markers of the presence or severity of NSAID-induced enteropathy were recognised. This trial is registered with DRKS00004940.

Whipple’s disease is a chronic infectious systemic disease caused by the bacterium Tropheryma whipplei. Nondeforming arthritis is frequently an initial complaint. Gastrointestinal and general symptoms include marked diarrhoea (with serious malabsorption), abdominal pain, prominent weight loss, and low-grade fever. Possible neurologic symptoms (up to 20%) might be associated with worse prognosis. Diagnosis is based on the clinical picture and small intestinal histology revealing foamy macrophages containing periodic-acid-Schiff- (PAS-) positive material. Long-term (up to one year) antibiotic therapy provides a favourable outcome in the vast majority of cases. This paper provides review of the literature and an analysis of our 5 patients recorded within a 20-year period at a tertiary gastroenterology centre. Patients were treated using i.v. penicillin G or amoxicillin-clavulanic acid + i.v. gentamicin for two weeks, followed by p.o. doxycycline (100 mg per day) plus p.o. salazopyrine (3 g per day) for 1 year. Full remission was achieved in all our patients.

Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is an extremely rare illness characterised by chronic or relapsing subileus status resulting from multiple small intestinal fibrous strictures and multiple shallow ulcers of the small bowel. The etiology is unknown and pathogenesis is not fully understood. Therapy with systemic glucocorticosteroids is the treatment of choice. However, most patients develop corticosteroid dependence. Deep enteroscopy enables precise diagnostic work, possible endoscopic treatment of stenoses; may obviate the need for surgery and prevent excessive small bowel resections.

We report a case of a 60-year-old man with acute myocardial infarction (AMI) treated using thrombolysis, and complicated by cardiogenic shock (CS). Plasma interleukin (IL) 1β, IL 6, IL 8, tumor necrosis factor alpha (TNFα), and soluble adhesion molecule (sICAM 1, sE-selectin) levels were measured at 3-h intervals. This observation showed the effect of AMI and CS on the plasma interleukin levels. Remarkable changes were found in the plasma TNF α level, which reached two significant peaks. The peak of the first elevation caused by AMI (80.11 pg/ml, vs. normal value 4.35 pg/ml, SD 21.3 pg/ml) was seen 6 h after the onset of the symptoms. After the period of significant decrease, TNF α level was increasing until the end of the observation period because of CS (the last TNF α level was 204.1 pg/ml). The plasma IL 1β level was continually increased during the period of observation (maximal IL 1β level 32.1 pg/ml, normal value

Abstract We assessed the diagnostic performance of the Narrow-Band Imaging (NBI) International Colorectal Endoscopic Classification (NICE) and the Japan NBI Expert Team classification (JNET) in predicting histological outcomes of advanced colorectal lesions. Additionally, we evaluated the sensitivity and positive predictive value (PPV) of the JNET and NICE classifications individually for high-grade lesions (including HGD adenomas, intramucosal carcinomas, and T1 carcinomas). This was a retrospective analysis of prospectively collected data, involving 211 patients (130 men, mean age 60 years) who underwent colonoscopy with endoscopic resection of advanced colorectal neoplasia (lesions ≥ 10 mm). Lesions were classified using both NICE and JNET criteria, and final histopathological results were used for comparison. Of the 257 lesions analyzed, the NICE classification accurately classifies a large proportion of lesions (93.8%). In JNET classification we observed 77.4% correctly classified lesions. Specifically, the sensitivity and positive predictive value (PPV) of the NICE classification for high-grade lesions were 100% and 24.4%, respectively. For the JNET classification, the sensitivity and PPV for high-grade lesions were 56.6% and 57.7%, respectively. The JNET classification, with a positive predictive value of 57.7% for high-grade colorectal lesions (including HGD adenomas, intramucosal carcinomas, and T1 carcinomas), should be used for decision-making regarding appropriate subsequent endoscopic therapy.

Background/Objectives: Tacrine is a centrally active non-competitive reversible acetylcholinesterase inhibitor. It also exerts antagonising activity against N-methyl-D-aspartate receptors. Tacrine was approved for the treatment of Alzheimer’s disease in 1993, but was withdrawn from clinical use in 2013 because of its hepatotoxicity and gastrointestinal side effects. Nevertheless, tacrine is currently facing a renewed wave of interest primarily due to several new tacrine-incorporated hybrids and derivates. There were two specific aims for this study: firstly, to explain the mechanisms of the adverse action of tacrine, as a distinctive example of a highly effective acetylcholinesterase inhibitor; and secondly to check whether luminal impedance planimetry is feasible for preclinical testing of possible side effects of compounds potentially toxic to the gastrointestinal tract. Methods: Six experimental pigs were used as the animal model in this study. Five major parameters were evaluated: luminal pressure (mmHg), estimated diameter (mm), cross-sectional area (mm2), distensibility (mm2/mmHg), and zone compliance (mm3/mmHg). All measurements were performed before and 360 min after intragastric administration of 200 mg tacrine (at the porcine tacrine Tmax). Results: This study consistently demonstrated an increase in luminal pressure (a directly measured indicator) for the particular balloon filling volumes used, and inversely a reciprocal decrease in the other parameters after tacrine administration. Conclusions: Endoscopic luminal impedance planimetry is a feasible method to evaluate functional response of the lower oesophageal sphincter to tacrine in experimental pigs. Tacrine did not compromise the function of the lower oesophageal sphincter either toward oesophageal spasms or, in contrast, decreased competence of the lower oesophageal sphincter.

[This corrects the article DOI: 10.1371/journal.pone.0286386.].

BackgroundRivastigmine is a pseudo-irreversible cholinesterase inhibitor used for therapy of Alzheimer's disease and non-Alzheimer dementia syndromes. In humans, rivastigmine can cause significant gastrointestinal side effects that can limit its clinical use. The aim of this study was to assess the impact of rivastigmine on gastric motor function by means of electrogastrography (EGG) in experimental pigs.MethodsSix experimental adult female pigs (Sus scrofa f. domestica, hybrids of Czech White and Landrace breeds; 3-month-old; mean weight 30.7 ± 1.2 kg) were enrolled into the study twice and created two experimental groups. In group A, a single intragastric dose of 6 mg rivastigmine hydrogen tartate was administered in the morning to fasting pigs before EGG recording. In group B, rivastigmine was administered to overnight fasting animals in a dietary bolus in the morning for 7 days (6 mg per day). On day 8, an intragastric dose of 12 mg rivastigmine was given in the morning to fasting pigs before EGG. EGG recording was accomplished by means of an EGG standalone system. Recordings from both groups were evaluated in dominant frequency and EGG power (areas of amplitudes).ResultsIn total, 1,980 one-minute EGG intervals were evaluated. In group A, basal EGG power (median 1290.5; interquartile range 736.5-2330 μV2) was significantly higher in comparison with the power of intervals T6 (882; 577-1375; p = 0.001) and T10 (992.5; 385-2859; p = 0.032). In group B, the dominant frequency increased significantly from basal values (1.97 ± 1.57 cycles per minute) to intervals T9 (3.26 ± 2.16; p < 0.001) and T10 (2.14 ± 1.16; p = 0.012), respectively. In group B, basal EGG power (median 1030.5; interquartile range 549-5093) was significantly higher in comparison with the power of intervals T7 (692.5; 434-1476; p = 0.002) and T8 (799; 435-1463 μV2; p = 0.004).ConclusionsBoth single as well as repeated intragastric administration of rivastigmine hydrogen tartrate caused a significant decrease of EGG power (areas of amplitudes) in experimental pigs. EGG power may serve as an indirect indicator of gastric motor competence. These findings might provide a possible explanation of rivastigmine-associated dyspepsia in humans.