Golimumab improves health-related quality of life of patients with moderate-to-severe ulcerative colitis: Results of the go-care study.

BACKGROUND: In recent years, improvement of Health-Related Quality of Life (HRQoL) in Ulcerative colitis (UC) has become a relevant measure for treatment efficacy. METHODS: We report results from a multicenter prospective study in Italy investigating HRQoL in adult patients with UC treated with golimumab (GLM). Patients who had shown clinical response after a 6-week induction phase (w0), were followed for an additional 48 weeks (w48) (total 54-week treatment). RESULTS: Of the 159 patients enrolled 90 completed the study. Compared to values at the beginning of treatment (n = 137), significant improvements were observed for mean total Inflammatory Bowel Disease Questionnaire (IBDQ) scores at w0 (168.5) and w48 (181.7). Patients with baseline PMS above the median tended to have greater improvements in IBDQ at w0 (OR 2.037, p = 0.033) and w48 (OR 3.292, p = 0.027). Compared to beginning of GLM treatment, the mean Full Mayo Score (FMS) decreased by 5.9 points at w48, while mean Partial Mayo Score (PMS) decreased by 3.9 points at w0 and by 4.9 points at w48. CONCLUSIONS: GLM improved HRQoL, disease activity and inflammatory biomarkers in UC patients with moderate-to-severely active disease. The greater the burden of disease activity at baseline, the greater the improvement of HRQoL after 24 and 48 weeks of treatment.

Supernatants of irritable bowel syndrome mucosal biopsies impair human colonic smooth muscle contractility.

BACKGROUND: Changes in intestinal motility are likely to contribute to irritable bowel syndrome (IBS) pathophysiology. The aim of the study was to investigate the effects of IBS mucosal supernatants on human colonic muscle contractility. METHODS: Supernatants were obtained from biopsies of 18 IBS patients-nine with constipation (IBS-C) and nine with diarrhea-predominant IBS (IBS-D)-and nine asymptomatic subjects, used as controls. Colonic circular smooth muscle strips or isolated cells (SMC) were exposed to control or IBS supernatants. Spontaneous phasic contractions on strips and morphofunctional parameters on cells were evaluated in basal conditions and in response to acetylcholine (Ach). Incubation with IBS supernatants was also conducted in the presence of antagonists and inhibitors (namely histamine, protease and prostaglandin antagonists, nuclear factor-kappa B inhibitor, catalase, NADPH oxidase inhibitor, and the cAMP- and/or cGMP-cyclase inhibitors). KEY RESULTS: Exposure to IBS-C and IBS-D supernatants induced a significant reduction in basal tone and Ach-elicited contraction of muscle strips and a significant shortening and impairment of Ach contraction of SMCs. The NADPH oxidase inhibitor prevented the effect of supernatants, while the protease antagonist only IBS-C effect. No effect was observed with the other antagonists and inhibitors. Dilution of IBS-D supernatants partially restored the effects only on SMCs, whereas dilution of IBS-C supernatants significantly reverted the effects on muscle strips and Ach-elicited response on SMC. CONCLUSIONS & INFERENCES: Supernatants from mucosal biopsies of IBS patients reduce colonic contractility. The observed impairment was concentration dependent, likely occurring through intracellular oxidative stress damage, involving different neuromotor mechanisms depending on the IBS subtype.

Breathing training on lower esophageal sphincter as a complementary treatment of gastroesophageal reflux disease (GERD): a systematic review.

OBJECTIVE: Gastroesophageal reflux disease (GERD) represents one of the most common gastrointestinal disorders, but is still a challenge to cure. Proton pump inhibitors (PPIs) are currently the GERD's standard treatment, although not successful in all patients; some concerns have been raised regarding their long term consumption. Recently, some studies showed the benefits of inspiratory muscle training in increasing the lower esophageal sphincter pressure in patients affected by GERD, thereby reducing their symptoms. MATERIALS AND METHODS: Relevant published studies were searched in Pubmed, Google Scholar, Ovid or Medical Subject Headings using the following keywords: "GERD" and physiotherapy", "GERD" and "exercise", "GERD" and "breathing", "GERD and "training". RESULTS: At the end of our selection process, four publications have been included for systematic review. All of them were prospective controlled studies, mainly based on the training of the diaphragm muscle. GERD symptoms, pH-manometry values and PPIs usage were assessed. CONCLUSIONS: Among the non-surgical, non-pharmacological treatment modalities, the breathing training on diaphragm could play an important role in selected patients to manage the symptoms of GERD.

Intra-bolus pressure and esophagogastric gradient, assessed with high-resolution manometry, are associated with acid exposure and proximal migration of refluxate.

Trans-sphincteric pressure gradient (TSPG) seems to play a relevant role in eliciting refluxes during transient lower esophageal sphincter relaxations (TLESRs). Intra-bolus pressure (IBP) is considered to be correlated to esophageal wall tone. We aimed to evaluate the relationship between IBP, TSPG during TLESRs and the dynamic properties of refluxate in gastroesophageal reflux disease. Sixteen non-erosive reflux disease (NERD), 10 erosive disease (ERD) patients and 12 healthy volunteers (HVs), underwent 24-hour impedance-pH monitoring and combined high-resolution manometry-impedance before and 60 minutes. After a meal, ERD patients presented a significantly lower mean IBP (4.7 ± 1.6 mmHg) respect to NERD patients (8.9 ± 2.8 mmHg) and HVs (9.2 ± 3.2 mmHg). NERD patients with physiological abnormal acid exposure time showed a mean IBP (10.4 ± 3.1 mmHg) significantly higher than that in NERD with pathological abnormal acid exposure time (5.1 ± 1.5 mmHg). The TSPG value was significantly higher during TLESRs accompanied by reflux than during TLESRs not associated with reflux, both in patients and in HVs. A significant direct correlation was found between IBP, TSPG and proximal spread of refluxes in patients and in HVs. Gastroesophageal reflux disease patients display different degrees of esophageal distension. An increased compliance of the distal esophagus may accommodate larger volumes of refluxate and likely facilitates the injuries development. Higher TSPG values appear to facilitate the occurrence of refluxes during TLESRs. In patients with NERD, higher TSPG and IBP values favor proximal spread of refluxate and hence may play a relevant role in symptom generation.

Reflux pattern and role of impedance-pH variables in predicting PPI response in patients with suspected GERD-related chronic cough.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) may contribute to the onset of chronic cough (CC); however, the multichannel intraluminal impedance-pH (MII-pH) monitoring is often within the normal range and the response to proton pump inhibitors (PPIs) unsatisfactory. The measure of impedance baseline (IB) increases the sensitivity of MII-pH in patients with typical symptoms. AIM: To evaluate the role of MII-pH variables, including IB, in predicting PPI response and to define the characteristics of the reflux pattern in CC patients. METHODS: Prospectively selected CC patients suspected GERD-related underwent MII-pH monitoring and, therefore, received a double dose of PPIs for at least 6 weeks. Patients filled symptom scores before MII-pH and after PPI therapy. MII-pH data were compared with those obtained in 60 non-erosive reflux disease patients with typical symptoms. RESULTS: A total of 156 CC patients entered the study: 68 (43.5%) responders and 88 (56.5%) nonresponders to PPIs. The number of reflux episodes was significantly higher in CC compared with that in typical symptoms patients. Nonresponder CC patients with a pathological acid exposure time (AET) and/or IB value were 43/88 (49%), while 15/88 (17%) presented only pathological AET (P < 0.001). CC patients with a pathological AET or IB, or with both a pathological AET and IB, showed a probability of PPI response twofold greater than patients with normal AET and IB. CONCLUSIONS: The presence of a pathological AET or pathological IB in CC patients is associated with a greater probability of PPI response. IB is a promising variable in patients with CC, as it increases the diagnostic yield of MII-pH and allows confirmation of the GERD diagnosis in these patients.

Experimental evidence and mathematical modeling of thermal effects on human colonic smooth muscle contractility.

It has been shown, in animal models, that gastrointestinal tract (GIT) motility is influenced by temperature; nevertheless, the basic mechanism governing thermal GIT smooth muscle responses has not been fully investigated. Studies based on physiologically tuned mathematical models have predicted that thermal inhomogeneity may induce an electrochemical destabilization of peristaltic activity. In the present study, the effect of thermal cooling on human colonic muscle strip (HCMS) contractility was studied. HCMSs were obtained from disease-free margins of resected segments for cancer. After removal of the mucosa and serosa layers, strips were mounted in separate chambers. After 30 min, spontaneous contractions developed, which were measured using force displacement transducers. Temperature was changed every hour (37, 34, and 31°C). The effect of cooling was analyzed on mean contractile activity, oscillation amplitude, frequency, and contraction to ACh (10(-5) M). At 37°C, HCMSs developed a stable phasic contraction (~0.02 Hz) with a significant ACh-elicited mean contractile response (31% and 22% compared with baseline in the circular and longitudinal axis, respectively). At a lower bath temperature, higher mean contractile amplitude was observed, and it increased in the presence of ACh (78% and 43% higher than the basal tone in the circular and longitudinal axis, respectively, at 31°C). A simplified thermochemomechanical model was tuned on experimental data characterizing the stress state coupling the intracellular Ca(2+) concentration to tissue temperature. In conclusion, acute thermal cooling affects colonic muscular function. Further studies are needed to establish the exact mechanisms involved to better understand clinical consequences of hypothermia on intestinal contractile activity.

Dilated intercellular space diameter as marker of reflux-related mucosal injury in children with chronic cough and gastro-oesophageal reflux disease.

BACKGROUND: The diagnostic corroboration of the relationship between gastro-oesophageal reflux disease (GERD) and chronic cough remains challenging. AIMS: To compare oesophageal mucosal intercellular space diameter (ISD) in children with GERD, children with gastro-oesophageal reflux (GER)-related cough (GrC) and a control group, and to explore the relationship between baseline impedance levels and dilated ISD in children with GER-related cough. METHODS: Forty children with GERD, 15 children with GrC and 12 controls prospectively underwent oesophagogastroduodenoscopy (EGD) with oesophageal biopsies taken 2-3 cm above squamocolumnar junction. ISD were quantified using transmission electron microscopy. Impedance-pH monitoring with evaluation of baseline impedance in the most distal impedance channel was performed in both patient groups. RESULTS: A significant difference in mean ISD values was found between GrC patients (0.9 ± 0.2 µm) and controls (0.5 ± 0.2 µm, P < 0.001), whereas there was no difference between GrC and GERD group (1 ± 0.3 µm, NS). No difference was found in the mean ISD between GrC children with or without pathological oesophageal acid exposure time (1 ± 0.3 vs. 0.9 ± 0.2 µm), and there was no correlation between ISD and any reflux parameter. Finally, there was no correlation between ISD and distal baseline impedance values (r:-0.35; NS). CONCLUSIONS: In children with reflux-related cough, dilated intercellular space diameter appears to be an objective and useful marker of oesophageal mucosal injury regardless of acid exposure, and its evaluation should be considered for those patients where the diagnosis is uncertain. In children with reflux-related cough, baseline impedance levels have no role in identifying reflux-induced oesophageal mucosal ultrastructural changes.

Acid reflux episodes sensitize the esophagus to perception of weakly acidic and mixed reflux in non-erosive reflux disease patients.

BACKGROUND: Non-erosive reflux disease (NERD) patients are more sensitive than erosive esophagitis patients to weakly acidic reflux and to the presence of gas in the refluxate. Intra-esophageal acid perfusion sensitizes esophageal receptors to mechanical and chemical stimuli. METHODS: To establish whether acid sensitization plays a role in the perception of weakly acidic and mixed reflux episodes, 29 NERD patients, responders and 14 non-responders to proton pump inhibitors (PPIs), underwent pH-impedance monitoring. Non-responders repeated the study while on PPIs. To assess the effect of acid exposure on symptom perception, the time period with pH below 4 was measured in 15- and 30-minute time-windows preceding the onset of each reflux episode. KEY RESULTS: Considering weakly acidic and mixed refluxes, both in responder and non-responder patients (off PPIs), the symptomatic refluxes were preceded by a significantly higher cumulative acid exposure than the asymptomatic refluxes. In all patients, following acid reflux, the percentage of symptomatic weakly acidic reflux episodes was significantly higher than that of asymptomatic refluxes. Non-responder patients, off-treatment, were characterized by a lower proportion of weakly acidic reflux and mixed reflux episodes. In the non-responder patients on PPI, only mixed and weakly symptomatic reflux episodes were preceded by a higher cumulative acid exposure. CONCLUSIONS & INFERENCES: In NERD patients, spontaneous acid reflux enhances subsequent reflux perception, regardless of acidity or liquid/mixed composition of episodes; in non-responder patients on PPIs, only the perception of mixed and weakly acidic reflux episodes seems to be mediated by a preceding acid exposure.

Lactobacillus rhamnosus protects human colonic muscle from pathogen lipopolysaccharide-induced damage.

BACKGROUND: Lactobacillus species might positively affect gastrointestinal motility. These Gram-positive bacteria bind Toll-like receptor 2 (TLR2) that elicits anti-inflammatory activity and exerts protective effects on damage induced by lipopolysaccharide (LPS). Whether such effect occurs in gastrointestinal smooth muscle has not been established yet. Aim of this study was to characterize the effects of Lactobacillus rhamnosus GG (LGG) and of supernatants harvested from LGG cultures on human colonic smooth muscle and to explore their protective activity against LPS-induced myogenic morpho-functional alterations. METHODS: The effects of LGG (ATCC 53103 strain) and of supernatants have been tested on both human colonic smooth muscle strips and isolated cells in the absence or presence of LPS obtained from a pathogenic strain of Escherichia coli. Their effects on myogenic morpho-functional properties, on LPS-induced NFκB activation, and on cytokine production have been evaluated. Toll-like receptor 2 expression has been analyzed by qPCR and flow cytometry. KEY RESULTS: Lactobacillus rhamnosus GG exerted negligible transient effects per se whereas it was capable of activating an intrinsic myogenic response counteracting LPS-induced alterations. In particular, both LGG and supernatants significantly reduced the LPS-induced morpho-functional alterations of muscle cells, i.e. cell shortening and inhibition of contractile response. They also hindered LPS-induced pro-inflammatory effects by decreasing pro-inflammatory transcription factor NFκB activation and pro-inflammatory cytokine IL-6 secretion, and restored the secretion levels of anti-inflammatory cytokine IL10. CONCLUSIONS & INFERENCES: Taken together these data demonstrate that LGG protects human colonic smooth muscle from LPS-induced myogenic damage and might be beneficial on intestinal motor disorders due to bacterial infection.

Relationship between baseline impedance levels and esophageal mucosal integrity in children with erosive and non-erosive reflux disease.

BACKGROUND: Baseline impedance measurement has been reported to be related to esophageal acid exposure and hypothesized to be a marker of microscopic changes of the esophageal mucosa. Aims of the study were to establish whether any relationship existed between the magnitude of intercellular space diameter (ISD) of esophageal mucosa and baseline impedance levels in children with gastro-esophageal reflux disease (GERD), and to compare baseline impedance levels between children with non erosive (NERD) and erosive (ERD) reflux disease. METHODS: Fifteen children (median age: 11.2 years) with NERD, and 11 with ERD (median age: 9.6 years) were prospectively studied. All patients underwent upper endoscopy. Biopsies were taken 2-3cm above the Z-line, and ISD was measured using transmission electron microscopy. All patients underwent impedance pH-monitoring, and baseline impedance levels were assessed in the most distal impedance channel. KEY RESULTS: Mean (±SD) ISD did not differ between NERD (1.0±0.3µm) and ERD (1.1 ± 0.3 µm, ns). Considering all patients together, no correlation was found between distal baseline impedance and ISD (r: -0.15; ns). Conversely, negative correlations were found between distal baseline impedance and acid exposure time (r: -0.76; P<0.001), long-lasting reflux episodes (r: -0.78; P<0.001), acid reflux episodes (r: -0.62; P<0.001), and acid clearance time (r: -0.79; P<0.001). Distal baseline impedance was significantly lower in ERD [1455 (947-2338) Ω] than in NERD children [3065 (2253-3771) Ω; P<0.01]. CONCLUSIONS & INFERENCES: In children with GERD baseline impedance levels are not useful in predicting reflux-induced ultrastructural changes in the esophageal mucosa, despite their ability to discriminate between NERD and ERD.

Platelet-activating factor and distinct chemokines are elevated in mucosal biopsies of erosive compared with non-erosive reflux disease patients and controls.

BACKGROUND: A distinction between symptomatic non-erosive reflux disease (NERD) and erosive esophagitis (EE) patients is supported by the presence of inflammatory response in the mucosa of EE patients, leading to a damage of mucosal integrity. To explore the underlying mechanism of this difference, we assessed inflammatory mediators in mucosal biopsies from EE and NERD patients and compared them with controls. METHODS: Nineteen NERD patients, 15 EE patients, and 16 healthy subjects underwent endoscopy after a 3-week washout from PPI or H(2) antagonists. Biopsies obtained from the distal esophagus were examined by quantitative real-time polymerase chain reaction (qPCR) and multiplex enzyme-linked immunosorbent assay for selected chemokines and lyso-PAF acetyltransferase (LysoPAF-AT), the enzyme responsible for production of platelet-activating factor (PAF). KEY RESULTS: Expression of LysoPAF-AT and multiple chemokines was significantly increased in mucosal biopsies derived from EE patients, when compared with NERD patients and healthy controls. Upregulated chemokines included interleukin 8, eotaxin-1, -2, and -3, macrophage inflammatory protein-1α (MIP-1α), and monocyte chemoattractant protein-1 (MCP-1). LysoPAF-AT and the chemokine profile in NERD patients were comparable with healthy controls. CONCLUSIONS & INFERENCES: Levels of selected cytokines and Lyso-PAF AT were significantly higher in the esophageal mucosa of EE patients compared with NERD and control patients. This difference may explain the distinct inflammatory response occurring in EE patients' mucosa. In contrast, as no significant differences existed between the levels of all mediators in NERD and control subjects, an inflammatory response does not appear to play a major role in the pathogenesis of the abnormalities found in NERD patients.

Primary aldosteronism: the role of confirmatory tests.

The high prevalence of primary aldosteronism among hypertensives justifies large scale screening by the aldosterone-renin ratio; however, this test is subject to several variables responsible for false-positive results. Functional tests to confirm autonomous aldosterone secretion are commonly used, with the fludrocortisone suppression test considered the gold standard, and saline infusion or captopril challenge, the most practical. However, each of these tests has sub-optimal sensitivity and specificity and none has been so far prospectively validated by comparing the results with the lateralization by adrenal vein sampling and the results of surgery. Their role in confirming the diagnosis of primary aldosteronism due to unilateral adenoma remains incompletely resolved.

Measurement of acid exposure of proximal esophagus: a better tool for diagnosing non-erosive reflux disease.

BACKGROUND: The sensitivity of 24-h pH monitoring is poor in non-erosive reflux disease (NERD). In NERD patients, the proximal extent of acid reflux is one of the main determinants of reflux perception. The present study was aimed to compare the diagnostic accuracy of acid exposure time (AET), at 5 cm above the lower esophageal sphincter, with those at 10 cm and at 3 cm below the upper esophageal sphincter as well as the reproducibility of these parameters. METHODS: A total of 93 consecutive NERD patients, with typical symptoms responsive to proton pump inhibitor treatment, and 40 controls underwent esophageal manometry and multi-channel 24-h pH-test; 13 patients underwent the same study on two occasions. Symptom association probability (SAP) values were evaluated at each esophageal level. KEY RESULTS: The ROC curve indicates that the area under the curve was 0.79 at distal (SE=0.039), 0.87 (SE=0.032) at proximal (P=0.029 vs distal), and 0.85 (SE=0.033) at very proximal esophagus (P =0.148). AET showed a reproducibility of 61% (Kappa 0.22) at distal esophagus, 77% (Kappa 0.45) at proximal and 53% (Kappa 0.05) at very proximal esophagus. The percentage of patients with a positive SAP was not significantly different when assessed at the distal compared with the proximal esophagus. CONCLUSIONS & INFERENCES: In NERD patients, the diagnostic yield of the pH test is significantly improved by the assessment of AET at the proximal esophagus. As this variable seems to be less affected by the day to day variability, it could be considered a reliable and useful diagnostic tool in NERD patients.

Progesterone receptors and serotonin levels in colon epithelial cells from females with slow transit constipation.

BACKGROUND: Females with slow transit constipation (STC) exhibit progesterone receptor (P4R) overexpression in colon muscle that impair their contractility. These studies examined whether these patients have an overexpression of P4R in epithelial cells and whether P4 affects the SERT-5-HT pathway. METHODS: Tissues were obtained from surgical specimens of seven females with STC and six controls. Feasibility studies were performed in biopsies from six patients with STC and three controls. P4R, SERT and TPH-1 mRNA and protein expression and 5-HT by ELISA were determined. Contraction was studied in normal muscle cells pretreated with P4 or buffer. Progesterone effects on SERT and 5-HT levels were studied in normal human mucosa in vitro and in wild and SERT knockout mice in vivo. KEY RESULTS: P4R was overexpressed in epithelial cells in STC compared with controls. The levels of SERT were lower and 5-HT higher in STC. In epithelial cells P4 treatment decreased SERT and increased mucosal 5-HT without affecting TPH-1. Progesterone impaired the contraction of normal muscle cells induced by Ach and 5-HT. Progesterone decreased SERT and increased 5-HT levels in the colon of wild mice in vivo but had no effect on the high basal levels of 5-HT in SERT knockout mice. CONCLUSIONS & INFERENCES: P4R are present in colon epithelial cells and are overexpressed in females with STC. These cells have reduced SERT and high 5-HT levels and normal TPH-1. These 5-HT signaling abnormalities are related to overexpression of P4R since they are reproduced in human epithelial cells in vitro and in mice in vivo.

Increased TRPV1 gene expression in esophageal mucosa of patients with non-erosive and erosive reflux disease.

BACKGROUND: Transient receptor potential channel vanilloid subfamily member-1 (TRPV1) may play a role in esophageal perception. TRPV1 mRNA and protein expression were examined in the esophageal mucosa of non-erosive reflux disease (NERD) and erosive esophagitis (EE) patients and correlated to esophageal acid exposure. METHODS: Seventeen NERD patients, eight EE patients and 10 healthy subjects underwent endoscopy after a 3-week washout from proton pump inhibitors or H2 antagonists. Biopsies, obtained from the distal esophagus, were used for conventional histology, for Western blot analysis and/or quantitative real-time polymerase chain reaction (qPCR). Overall 13 NERD patients, four EE patients and five controls underwent ambulatory pH-testing. KEY RESULTS: TRPV1 expression was increased in all NERD and EE patients, as measured by Western blot analysis (0.65 +/- 0.07 and 0.8 +/- 0.05 VS 0.34 +/- 0.04 in controls; P < 0.01) and by qPCR (1.98 +/- 0.21 and 2.52 +/- 0.46 VS 1.00 +/- 0.06; P < 0.01). Neutrophilic infiltration, in the mucosa, was detected only in EE patients. CONCLUSIONS & INFERENCES: Non-erosive reflux disease and EE patients presented increased TRPV1 receptors mRNA and protein, although no correlation with acid exposure was demonstrated. Increased TRPV1 in the esophageal mucosa may contribute to symptoms both in NERD and EE patients and possibly account for peripheral mechanisms responsible for esophageal hypersensitivity in NERD patients.

Effect of ursodeoxycholic acid on inflammatory infiltrate in gallbladder muscle of cholesterol gallstone patients.

BACKGROUND: Reduced gallbladder (GB) contractility and chronic inflammatory changes in the mucosa have been reported in patients with cholesterol gallstones (GS). Ursodeoxycholic acid (UDCA) restores GB contractility and antagonises liver macrophage activation. In the colon, hydrophobic bile acid, not hydrophilic UDCA, induces mast cell degranulation. We studied the presence of monocyte/macrophage infiltrate, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expression, the number of total and degranulated mast cells in the GB muscle layer of cholesterol GS patients, and the effect of UDCA administration. METHODS: Gallbladder tissue was obtained from cholesterol GS patients, either treated or untreated with UDCA (10 mg kg(-1) day(-1)) for 30 days prior to surgery. Gallbladders removed for neoplastic diseases, not involving GB, were evaluated for control purposes. The presence of monocytes/macrophages (CD68 positive), granulocytes, and mast cells, and the COX-2 and iNOS expression, was determined immunohistochemically. KEY RESULTS: The number of CD68, granulocytes, mast cells, COX-2 and iNOS positive cells was significantly higher in the muscle layer of GS patients than in controls. Compared to untreated patients, those treated with UDCA showed significantly lower levels of CD68, COX-2 positive cells and degranulated mast cells and a lesser number of iNOS positive cells and granulocytes. CONCLUSIONS & INFERENCES: An inflammatory monocyte/macrophage, mast cell and granulocyte infiltrate is present in the GB muscle layer of GS patients. Ursodeoxycholic acid decreases macrophages, degranulated mast cells and COX-2 expression. These results suggest that monocytes/macrophages and degranulating mast cells contribute to muscle cell dysfunction in cholesterol GS patients and support the anti-inflammatory effect of UDCA.