Role of impaired gastric accommodation to a meal in functional dyspepsia

BACKGROUND & AIMS: Impaired accommodation of the proximal stomach to a meal has been reported in functional dyspepsia, but its relevance to symptoms is unclear. The aim of this study was to test the hypothesis that impaired gastric accommodation causes early satiety. METHODS: A gastric barostat was used to study postprandial fundus relaxation in 35 healthy subjects and 40 patients with functional dyspepsia. Gastric emptying, Helicobacter pylori status, sensitivity to gastric distention, and a dyspepsia symptom score were obtained from all patients. In addition, the effect of sumatriptan, a fundus-relaxing 5-hydroxytryptamine1 agonist, on gastric accommodation and on early satiety in dyspeptic patients was studied. RESULTS: Impaired gastric accommodation to a meal was found in 40% of the patients. In univariate analysis, this was associated with early satiety and weight loss but not with hypersensitivity to gastric distention, presence of H. pylori, or delayed gastric emptying. In a multivariate analysis, only early satiety was associated with impaired gastric accommodation. Sumatriptan restored gastric accommodation, thereby significantly improving meal-induced satiety. CONCLUSIONS: Impaired relaxation of the proximal stomach to a meal is present in a high proportion of patients with functional dyspepsia. It is associated with symptoms of early satiety. Restoring gastric accommodation with a fundus-relaxing drug improves early satiety.     

Role of gastric emptying in functional dyspepsia: a scintigraphic study of 94 subjects

1. Flupirtine is an analgesic agent which exhibits neuronal cytoprotective activity and may have value in the treatment of conditions involving cell injury and apoptosis. Since flupirtine has no action on known receptor sites we have investigated the effect of this drug on mitochondrial membrane potential, and the changes in intramitochondrial calcium concentration in particular. 2. The findings show that flupirtine increases Ca2+ uptake in mitochondria in vitro. At clinically relevant flupirtine concentrations, corresponding to flupirtine levels in vitro of 0.2 to 10 nmol mg(-1) mitochondrial protein, there was a 2 to 3 fold increase in mitochondrial calcium levels (P<0.01). At supra-physiological flupirtine concentrations of 20 nmol mg(-1) mitochondrial protein and above, the mitochondrial calcium concentrations were indistinguishable from those in untreated mitochondria. 3. Mitochondrial membrane potential closely paralleled the changes in mitochondrial calcium levels showing a 20% (P<0.01) increase when the flupirtine concentration was raised from 0.2 nmol to 10 nmol mg(-1) mitochondrial protein and a return to control values at 20 nmol mg(-1) protein. 4. The increase in mitochondrial calcium uptake and membrane potential were accompanied by an increase in mitochondrial ATP synthesis (30%; P<0.05) and a similar percentage reduction in mitochondrial volume. 5. Calcium at 80 and 160 nmol mg(-1) mitochondrial protein decreased ATP synthesis by 20-25% (P<0.001). This decrease was prevented or diminished if flupirtine at 10 nmol mg(-1) protein was added before the addition of calcium. 6. Since intracellular levels of flupirtine in intact cells never exceeded 10 nmol mg(-1) mitochondrial protein, these findings are supportive evidence for an in vivo cytoprotective action of flupirtine at the mitochondrial level.     

Timing of postprandial dyspeptic symptoms and transpyloric passage of gastric contents

BACKGROUND: Patients with functional dyspepsia often experience early satiety and discomfort after a meal. The role of early gastric emptying in symptom generation is not known. Our aim was to relate timing of symptoms and early postprandial emptying in functional dyspepsia. METHODS: Twelve patients with functional dyspepsia were investigated during 3 min of fasting, during 3 min of ingesting 500 ml of a meat soup, and during the first 10 min postprandially by means of duplex sonography. RESULTS: Gastric emptying commenced on average 52 sec after the start of ingestion. Transpyloric movements of gastric contents unrelated to peristalsis (that is, alternating transpyloric emptying and reflux within a common chamber created by the terminal antrum, the pylorus, and the duodenal bulb) appeared before peristaltic-related emptying, which commenced after on average 116 sec. In all patients epigastric, meal-related discomfort was experienced after the commencement of transpyloric emptying, on average after 143 sec. A negative correlation was found between intensity of fullness and duration of presymptomatic transpyloric movements of gastric contents (that is, the duodenal 'tasting' period). CONCLUSIONS: The early occurrence of meal-related symptoms suggests that gastric distension is the main factor in symptom generation. However, the onset of symptoms after the commencement of gastric emptying suggests that intestinal tasting receptors are involved in symptom generation. The inverse relationship between the duration of the tasting period and symptom intensity suggests that the time allowed for duodenal tasting might be too short in patients with FD.     

Upper digestive tract dyspepsia and early gastric cancer

AIM: The study of the frequency and evolution of upper digestive tract dyspepsia in a group of patients operated for early gastric cancer (EGC) and to perform a strategy of diagnosis for the patients with long term upper digestive tract dyspepsia. METHODS: Clinical data of 35 patients operated for EGC were retrospectively evaluated. The frequency, characteristics and evolution time of upper digestive tract dyspepsia, main when it began more than 6 months before surgery, were analyzed. Radiologic and endoscopic exams carried out for diagnosis were also evaluated. Histological diagnosis of surgical specimens were considered, looking for the presence of chronic atrophic gastritis, intestinal metaplasia, and peptic gastric ulcer. RESULTS: Long-term upper digestive tract dyspepsia was present in 27 patients (mean evolution time of 43.4 months). Clinical changes of previous symptoms that suggested gastric carcinoma were not found in 15 patients. Concurrent peptic gastric carcinoma were not found in 15 patients. Concurrent peptic gastric ulcer along with EGC was diagnosed by histology in 11 patients, and chronic atrophic gastritis and intestinal metaplasia were both present in the non-tumoral gastric mucosa in all cases. CONCLUSIONS: 1) Unspecific upper digestive tract dyspepsia is frequently found in patients with EGC. 2) Endoscopy should be the first exam performed in patients with upper digestive tract dyspepsia. 3) The patients with gastric ulcer, chronic atrophic gastritis or intestinal metaplasia must be submitted to sequential endoscopic follow-up.     

Role of endogenous prostaglandins in secretin- and plaunotol-induced inhibition of gastric acid secretion in the rat

We investigated the role of endogenous prostaglandins in the inhibitory effect of exogenous secretin and the antiulcer agent plaunotol on gastric acid secretion in the rat. Intravenous infusion of secretin (0.05 CU/kg/h) and intraduodenal administration of the secretin-releasing agent, plaunotol (320 mg/h), resulted in significant inhibition of gastric acid secretion stimulated by intravenous infusion of pentagastrin (0.3 micrograms/kg/h), and this was accompanied by an increase in the prostaglandin E2 content of the gastric mucosa. Intraduodenal administration of plaunotol (320 mg/h) produced plasma secretin levels comparable to the levels achieved by intravenous infusion of secretin (0.05 CU/kg/h). Intravenous administration of prostaglandin synthesis inhibitor, indomethacin (2 mg/kg + 1 mg/kg/h), completely abolished both the inhibitory action of secretin and plaunotol on gastric acid secretion, and the increase in gastric mucosa prostaglandin E2 induced by secretin and plaunotol. The results indicate that endogenous prostaglandins play a significant role in the inhibitory action of exogenous and plaunotol-released endogenous secretin in the rat.     

Role of gastrin/CCK-B receptor in the regulation of gastric acid secretion in rat

The aim of this study was to investigate whether gastrin regulates morphological changes and alpha-subunit gene expression in parietal cells through the gastrin/CCK-B receptor on enterochromaffin-like cells by histamine release. Treatment with 100 mg/kg of YM022, a potent and selective gastrin/CCK-B receptor antagonist, for one week in rats did not alter mRNA levels of histidine decarboxylase or H+, K+-ATPase. However, parietal cell morphology predominantly changed to the resting form, although the serum gastrin concentration was significantly increased. Additional treatment with YM022 and oral omeprazole, 100 mg/kg, for one week markedly suppressed the increases of mRNA levels of histidine decarboxylase and H+, K+-ATPase and completely blocked the morphological transformation of the parietal cells to a stimulated form induced by treatment with omeprazole alone. This indicates that the morphological transformation of parietal cells to an activated form with a subsequent increase in H+, K+-ATPase synthesis caused by hypergastrinemia is mediated by increased histidine decarboxylase gene expression in enterochromaffin-like cells via gastrin/CCK-B receptors.     

Disturbed solid-phase gastric emptying in functional dyspepsia: a meta-analysis

Functional dyspepsia is a common disorder with a diverse pathophysiological background, but the role of motility disorders in functional dyspepsia remains unclear. We aimed to quantify the relationship between disturbed gastric emptying and functional dyspepsia, using a meta-analytic approach. Through a structured literature search of Medline and Embase from 1983 to 1996, we selected all studies in which scintigraphic solid-phase gastric emptying was measured in both functional dyspeptic patients and controls. Seventeen studies involving 868 dyspeptic patients and 397 controls were pooled. Gastric emptying in patients with functional dyspepsia was 1.46 (1.23-1.69) times slower than controls; the proportion of patients with abnormally slow emptying was either 37% (34-40%, simple numeric pooling) or 39% (29-49%, weighted pooling). We conclude that gastric emptying of solids in patients with functional dyspepsia is 1.5 times slower than in healthy controls and that a significant delay of emptying is present in almost 40% of patients with functional dyspepsia.     

Impaired postprandial gastric slow waves in patients with functional dyspepsia

The aim of this study was to investigate gastric myoelectrical activity in patients with functional dyspepsia. Thirteen healthy subjects and 14 patients with functional dyspepsia participated in the study. The electrogastrogram (EGG) recording was made in each subject for 30 min in the fasting state and 120 min after a standard test meal of 475 calories. Spectral analysis methods were applied to derive quantitative EGG parameters. There was no difference in the EGG between the patients and controls in the fasting state. However, abnormalities in the postprandial EGG were found in the patients. The percentage of 2-4 cpm waves was significantly lower (74.4+/-4.0% vs 85.7+/-1.6%, P < 0.03) and the postprandial increase in EGG dominant power was significantly less (-0.52+/-0.92 dB vs 2.24+/-0.88 dB, P < 0.03) in patients than in controls. It was also found that the percentage of postprandial 2-4 cpm waves could be used to differentiate the patients with functional dyspepsia from the healthy controls with a specificity of 100% and a sensitivity of 43%. It was concluded that a subset of patients with functional dyspepsia have impaired gastric myoelectrical activity in the fed state.     

Isoquinoline derivatives as endogenous neurotoxins in the aetiology of Parkinson's disease

The cause of neurodegeneration in Parkinson's disease (PD) remains unknown. However, isoquinoline derivatives structurally related to the selective dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite, 1-methyl-4-phenylpyridinim (MPP+), have emerged as candidate endogenous neurotoxins causing nigral cell death in Parkinson's disease. Isoquinoline derivatives are widely distributed in the environment, being present in many plants and foodstuffs, and readily cross the blood-brain barrier. These compounds occur naturally in human brain where they are synthesized by non-enzymatic condensation of biogenic amines (e.g. catecholamines and phenylethylamine) with aldehydes, and are metabolized by cytochrome P450s and N-methyltransferases. In addition, isoquinoline derivatives are oxidized by monoamine oxidases to produce isoquinolinium cations with the concomitant generation of reactive oxygen species. Neutral and quaternary isoquinoline derivatives accumulate in dopaminergic nerve terminals via the dopamine re-uptake system, for which they have moderate to poor affinity as substrates. Several isoquinoline derivatives are selective and more potent inhibitors of NADH ubiquinone reductase (complex I) and alpha-ketoglutarate dehydrogenase activity in mitochondrial fragments than MPP+, and lipophilicity appears to be important for complex I inhibition by isoquinoline derivatives. However, compared with MPP+, isoquinoline derivatives are selective but less potent inhibitors of NADH-linked respiration in intact mitochondria, and this appears to be a consequence of their rate-limiting ability to cross mitochondrial membranes. Although both active and passive processes are involved in the accumulation of isoquinoline derivatives in mitochondria, inhibition of respiration is determined by steric rather than electrostatic properties. Compared with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or MPP+, isoquinoline derivatives show selective but relatively weak toxicity to dopamine-containing cells in culture and following systemic or intracerebral administration to experimental animals, which appears to be a consequence of poor sequestration of isoquinoline derivatives by mitochondria and by dopamine-containing neurones. In conclusion, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-like cytotoxic characteristics of isoquinoline derivatives and the endogenous/environmental presence of these compounds make it conceivable that high concentrations of and/or prolonged exposure to isoquinoline derivatives might cause neurodegeneration and Parkinson's disease in humans.     

Role of acid and salivary epidermal growth factor in gastric mucosal adaptation to naproxen in man

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) frequently damage the gastrointestinal tract, but with continued administration this usually resolves by a process of adaptation. There is evidence that the acute injury can be reduced by acid suppression, and animal models have shown that salivary epidermal growth factor (EGF) is an important factor in gastric mucosal adaptation. We therefore wanted to assess the effect of acid suppression and salivary EGF output during naproxen-induced acute gastric injury and subsequent adaptation. METHODS: Healthy subjects were given a 14-day course of naproxen with different regimens of ranitidine and placebo. Before and on three occasions during treatment subjects provided a salivary sample for EGF and underwent gastroscopy to assess gastric damage. RESULTS: Similar gastric damage occurred after 24 h in all groups and resolved in most subjects. Base-line salivary EGF output was similar in all groups but increased in the placebo/ranitidine group on day 3 and in the ranitidine group on day 9. CONCLUSIONS: Acid suppression with ranitidine did not prevent acute gastric injury. Adaptation may be associated with an increase in salivary EGF output.     

Study of gastric and gallbladder kinetics with real-time ultrasonography in cases of functional dyspepsia

Gastric and gallbladder emptying in 113 patients with functional dyspepsia (FD) were evaluated by real-time ultrasonography (RUS) after a liquid-fat meal by the patients, and compared with 15 healthy volunteers. The results showed that in FD group 69 patients (61.06%) had delayed gastric emptying, and 28 patients (24.77%) had gallbladder hypokinesia. Among them both delayed gastric emptying and gallbladder hypokinesia were found in 11 patients (9.7%), 44 patients (38.93%) had normal gastric emptying and 85 patients (75.22%) had normal gallbladder emptying.     

Nomenclature of dyspepsia, dyspepsia subgroups and functional dyspepsia: clarifying the concepts

Aging implies changes in joint components over a continuum of time that contribute later in life to an increasing frequency of clinical complaints and impairments in function and mobility. This article considers how aging appears to modify the articular cartilage, subchondral bone, muscle, the soft tissues, synovial membrane, and synovial fluid. Whether the changes in aging inevitably progress through an intermediary phase of "degenerated cartilage" to the fibrillated state of osteoarthritis is not clear.     

Functional dyspepsia, gastric emptying of solids, and Helicobacter pylori infection

The origin of functional dyspepsia (FD) is unknown, however, abnormal gastric emptying and infection by H. pylori have been suggested as possible causes. OBJECTIVE: The aim of this study was to test the hypothesis that infection by H. pylori could be related to alterations in gastric emptying of solids and play a role in the pathophysiology of dyspepsia. METHODS: Studies were performed on 12 controls: 6 males, 6 females, age 40 +/- 13, and on 45 FD patients: 15 males and 30 females, age 43.5 +/- 12. Clinical criteria for FD diagnosis were post-prandial epigastric pain, nausea, vomiting or epigastric bloating, with normal blood test, upper endoscopy and abdominal ultrasound. Diagnosis of H. pylori infection was either by growth positive on culture of antral biopsy or by all of the following: on Gram stain, urease test positive and visualization of microorganisms in the antral biopsy. Gastric emptying of solids was studied with a radio-nuclide technique. Patients were prospectively classified in 4 groups according to the main symptom: reflux-like, ulcer-like, dysmotility, and non-specific. RESULTS: H. pylori infection was observed in 21/32 (66%) FD patients. No significant differences in the gastric emptying of solids between the control group and patients with FD (tl/2 80 +/- 17 minutes vs 75 +/- 16 min). The presence of H. pylori infection did not influence gastric emptying rates (78 +/- 16 minutes in infected patients vs 73 +/- 15 min in non infected patients). Gastric emptying times were similar among the four subgroups of FD patients. CONCLUSIONS: No significant differences in gastric emptying of solids were found in H. pylori infected persons as compared with the controls. These findings suggest that H. pylori infection and/or changes in gastric emptying of solids do not play a role in the pathophysiology of FD.     

Helicobacter pylori infection and gastric emptying of indigestible solids in patients with dysmotility-like dyspepsia

BACKGROUND: The role of Helicobacter pylori and gastric motility in dysmotility-like dyspepsia is unclear. The aim of this study was to determine whether delayed gastric emptying of indigestible solids and H. pylori infection are associated with dysmotility-like dyspepsia. METHODS: Thirty-two healthy volunteers and 72 patients fulfilling the criteria of dysmotility-like dyspepsia received a gastric emptying test using radiopaque markers, and the H. pylori status was determined by histology. RESULTS: Twenty-seven percent of volunteers were H. pylori-positive, compared with 32% in the dyspeptic groups (P = NS). Gastric emptying was significantly slower in dyspeptic patients than controls and in H. pylori-positive patients than H. pylori-negative patients. Subjects with gastroparesis have a higher chance of developing dysmotility-like dyspepsia (odds ratio (OR), 2.5) than subjects with normal gastric emptying. Subjects with H. pylori and gastroparesis have an increased likelihood of developing dysmotility-like dyspepsia (OR, 4.3) than if either factor were present alone. CONCLUSION: Our data suggest that gastroparesis alone and gastroparesis and H. pylori infection are associated with dysmotility-like dyspepsia.     

Effect of hyperthyroidism on antral myoelectrical activity, gastric emptying and dyspepsia in man

BACKGROUND/AIMS: The objective of the present study was to investigate the effect of hyperthyroidism on antral myoelectrical activity, gastric emptying and dyspepsia in man. METHODOLOGY: Twenty-three patients with manifest hyperthyroidism and dyspepsia confirmed by a standardized protocol were studied by electrogastrography (EGG). The following EGG parameters were determined: dominant frequency (DF cycles per minute (cpm), DF (%) in the normal range (2-4 cpm)), bradygastria (< 2 cpm), tachygastria (4-10 cpm), dominant frequency instability coefficient (DFIC), and postprandial to fasting power ratio. Data were correlated to results obtained in 18 age- and gender-matched controls. In 10 patients, a control measurement was performed after antithyroid therapy. In addition, in 15 consecutive patients, EGG data were compared to gastric emptying of radionuclides recorded simultaneously (gamma camera). RESULTS: Hyperthyroid patients revealed a significant increase in preprandial DF, and in pre- and post-prandial tachygastrias compared to controls (3.3 cpm vs 3.1 cpm; 8.8% vs 3.5%; 12.3% vs 3.5%; p < 0.05). After antithyroid therapy, postprandial tachygastrias were reduced significantly. About 50% of the patients exhibited delayed gastric emptying compared to previously evaluated normal values (t 60 nuclide retention: > 68%). However, these patients did not differ in tachygastria and the other EGG parameters from those with normal gastric emptying (p > 0.05). Both EGG and radioscintigraphy did not correlate significantly with dyspepsia. CONCLUSIONS: Dyspeptic patients with hyperthyroidism frequently display tachygastria and delayed gastric emptying. However, tachygastria has no important effect on gastric motor activity in hyperthyroidism.     

Proximal and distal gastric distension in normal subjects and H. pylori-positive and -negative dyspeptic patients and correlation with symptoms

Aim of the study was to analyze gastric distension with water in H. pylori-positive and -negative dyspeptic patients and normal subjects and the correlation with symptoms. Twenty dyspeptic patients and 19 normal subjects were studied. H. pylori was determined in each dyspeptic patient with the rapid urea test at endoscopy. Gastric distension was evaluated by real-time ultrasonography with the ingestion of stepwise-increasing amounts of water up to a total of 600 ml. During distension, the symptom score was evaluated as well. The proximal stomach was significantly smaller in dyspeptic patients than in healthy controls, at 100-600 ml water (P<0.01). A larger distal stomach was observed at 500 and 600 ml of water (P<0.01). The score of bloating and fullness was greater in dyspeptics than in controls at 300 and 600 ml of water distension. The symptoms score was linearly correlated with proximal and distal gastric measurements in dyspeptic patients and in controls. No significant difference was found in dyspeptic patients regarding the H. pylori status. In conclusion, dyspeptic patients show a defective adaptation of the whole stomach to water distension and an increased symptom perception score as compared to controls. H. pylori infection does not seem to be a determining factor in these observed findings.     

Does Helicobacter pylori infection affect gastric emptying in patients with functional dyspepsia?

The objectives of the study were first, to determine if gastric emptying was altered in patients with functional dyspepsia with and without Helicobacter pylori infection compared with normal healthy volunteers; and second, to determine if there were further alterations in gastric emptying when the infection was eradicated. Gastric emptying was measured using a 99mtechnetium radiolabelled solid meal and gastric emptying time was measured as t1/2, viz. time taken for half the radiolabelled meal to be emptied from the stomach. The mean gastric emptying time for H. pylori-positive patients (n=20) was 56.4+/-24.8 min; H. pylori-negative patients (n=19) 67.8+/-31.8 min; and normal controls (n=20) 58.8+/-18.8min. No significant difference was obtained between the groups (ANOVA; P=0.348). Thirteen of 18 H. pylori-positive patients successfully eradicated the infection following treatment with omeprazole 40 mg o.m. and amoxycillin 500 mg t.d.s. for 2 weeks. The mean difference in the gastric emptying time before and after H. pylori eradication was 23.9+/-13.2 min (P= 0.556). There was no significant difference in the frequency of specific dyspeptic symptoms as well as the overall mean symptom score between the H. pylori-positive and -negative patients. Gastric emptying was not different between patients with functional dyspepsia and normal controls. Helicobacter pylori infection does not appear to affect gastric emptying in patients with functional dyspepsia.     

Patterns of symptoms in functional dyspepsia: role of Helicobacter pylori infection and delayed gastric emptying

OBJECTIVE: Functional dyspepsia (FD) is a syndrome in which several causes are probably involved. Our aim was to investigate the association between specific dyspeptic symptoms and Helicobacter pylori infection or delayed gastric emptying. METHODS: Nine hundred thirty-five consecutive outpatients with unexplained dyspepsia were studied. After appropriate investigation, 304 patients were diagnosed as affected by chronic FD and were tested for H. pylori infection and gastric emptying of solids by means of 13C-urea and 13C-octanoic acid breath tests. Four dyspeptic symptoms (epigastric pain or burning, postprandial fullness, nausea, and vomiting) were scored as absent, mild, moderate, or severe (0-3) according to their influence on the patients' activities. Symptoms of irritable bowel syndrome and gastroesophageal reflux disease were also assessed. On the basis of symptom scores, three groups were identified: "prevalent pain" (10.5%), "prevalent discomfort" (32.6 %), and "unclassifiable" dyspepsia (56.9%). RESULTS: Of the 304 patients with FD, 208 (68.4 %) were H. pylori-positive on urea breath test. Gastric emptying was delayed in 99 subjects (32.6%). Patients with "prevalent pain" were infected significantly more often (81.2% vs 59.6%; p = 0.026) and less frequently had delayed gastric emptying (6.2% vs 40.4%; p = 0.0001) than those with "prevalent discomfort." H. pylori infection was independently associated with age > or =40 yr and epigastric pain or burning > or =2 (odds ratio [OR] and 95% confidence interval [CI] 4.09 [2.39-7.00] and 1.70 [1.04-2.77], respectively). Delayed gastric emptying was independently associated with a cumulative score > or =6 for postprandial fullness, nausea, and vomiting (OR [95% CI]: 3.13 [1.06-9.18]). H. pylori status had no influence on gastric emptying. Logistic regression analysis showed that delayed gastric emptying, female sex, and concomitant symptoms of inflammatory bowel syndrome were independently associated with a cumulative score > or =6 for postprandial fullness, nausea, and vomiting (p = 0.0281, p = 0.0387, and p = 0.0316, respectively). Moreover, concomitant symptoms of gastroesophageal reflux disease, female sex, and H. pylori infection were independently associated with epigastric pain or burning > or =2 (p = 0.002, p = 0.0001, and p = 0.0875, respectively). CONCLUSIONS: Two subsets of FD patients have been identified on the basis of symptoms. One subgroup is mainly characterized by "prevalent pain," H. pylori infection, and normal gastric emptying; the other one demonstrates "prevalent discomfort" and delayed gastric emptying. These findings shed some light on possible etiopathogenetic mechanisms of FD.