Efficacy of ustekinumab in the treatment of patients with Crohn's disease with failure to previous conventional or biologic therapy: a prospective observational real-life study.

Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved by FDA and EMA for the treatment of moderate to severe Crohn's disease (CD). Whether UST is effective in inducing deep remission, including mucosal healing and transmural healing, in patients with CD in a real life setting is not completely clear. This study was performed on 92 subjects with confirmed diagnosis of moderate to severe Crohn's disease and no neoplasia. Before inclusion, all patients had been exposed and had failed to respond to conventional and/or at least one biological therapy. All patients underwent endoscopic examination and bowel MRI and ultrasonography at baseline (T0). At week 52 (T52), patients underwent colonoscopy for assessment of mucosal healing and MRI or ultrasonography for assessment of transmural healing. CDAI was used for the assessment of clinical response and clinical remission. SES-CD was used to assess endoscopic response and remission. Incidence of treatment-related adverse events (TRAEs) was recorded during the study period. Clinical response at week 52 was achieved in 38 (50.5%) patients and clinical remission in 29 (39%). Twenty-six (34%) patients showed mucosal healing, 34 (45%) showed partial endoscopic response. We observed a reduction in SES-CD of at least 50% in 34 (45%) patients as well as an SES-CD ≤ 2 in 26 (35%) patients. All patients with mucosal healing also showed transmural healing. No major TRAEs were observed during treatment. In this multicenter, real life study, we show that UST was well tolerated and effective in inducing clinical response and clinical remission in patients with moderate to severe CD who had previously failed to respond to conventional or biologic therapy. UST showed limited efficacy in inducing deep remission (i.e. mucosal+transmural healing).

Histopathology of Celiac Disease. Position Statements of the Italian Group of Gastrointestinal Pathologists (GIPAD-SIAPEC).

Celiac Disease (CeD) is an immune-mediated inflammatory disorder of the small intestine, affecting genetically susceptible individuals when exposed to gluten. Small intestinal biopsy interpretation has been the "gold standard" for celiac disease (CeD) for over 50 years. Despite today's availability of sensitive and specific serological tests, the histopathological features from mucosal biopsy play a key role in diagnosing when CeD is suspected. Such a diagnostic approach requires a multidisciplinary team to optimize both tissue sampling and interpretation via the interaction between the pathologist and the gastroenterologist. Pathologists of the Italian Group of Gastrointestinal Pathology (GIPAD-SIAPEC), together with a member (TR) of the Italian Society of Technicians (AITIC) and an expert gastroenterologist (CC), provide position statements as a practical tool for reading and interpreting the report. Moreover, a position statement was formulated about the recently described condition known as Non-Celiac Gluten Sensitivity (NCGS). Within such a diagnostic setting, both the architectural abnormalities of the duodenal mucosa, namely glandular hyperplasia, and villous atrophy and the number of intraepithelial T-lymphocytes should be well highlighted. Ancillary tests such as anti-CD3 stain are useful for an accurate count of the intraepithelial T lymphocytes when CeD or NCGS is suspected. Moreover, anti-CD3 and anti-CD8 stains are recommended in patients not responding to the gluten-free diet (GFD) to confirm a diagnosis of Refractory Celiac Disease (RCeD). Diagnostic clues about the differential diagnosis of both CeD and RCeD have also been rendered.

Effects of nanosilver on Mytilus galloprovincialis hemocytes and early embryo development.

Silver nanoparticles (AgNP), one of the main nanomaterials for production and use, are expected to reach the aquatic environment, representing a potential threat to aquatic organisms. In this study, the effects of bare AgNPs (47 nm) on the marine mussel Mytilus galloprovincialis were evaluated at the cellular and whole organism level utilizing both immune cells (hemocytes) and developing embryos. The effects were compared with those of ionic Ag+(AgNO3). In vitro short-term exposure (30 min) of hemocytes to AgNPs induced small lysosomal membrane destabilization (LMS EC50 = 273.1 µg/mL) and did not affect other immune parameters (phagocytosis and ROS production). Responses were little affected by hemolymph serum (HS) as exposure medium in comparison to ASW. However, AgNPs significantly affected mitochondrial membrane potential and actin cytoskeleton at lower concentrations. AgNO3 showed much higher toxicity, with an EC50 = 1.23 µg/mL for LMS, decreased phagocytosis and induced mitochondrial and cytoskeletal damage at similar concentrations. Both AgNPs and AgNO3 significantly affected Mytilus embryo development, with EC50 = 23.7 and 1 µg/L, respectively. AgNPs caused malformations and developmental delay, but no mortality, whereas AgNO3 mainly induced shell malformations followed by developmental arrest or death. Overall, the results indicate little toxicity of AgNPs compared with AgNO3; moreover, the mechanisms of action of AgNP appeared to be distinct from those of Ag+. The results indicate little contribution of released Ag+ in our experimental conditions. These data provide a further insight into potential impact of AgNPs in marine invertebrates.

Prevalence of Sleep Bruxism in IBD Patients and Its Correlation to Other Dental Disorders and Quality of Life.

BACKGROUND: Patients with inflammatory bowel diseases could experience mouth and teeth disorders and alterations in psychological mood. Vice versa, the psychological status may influence the presence of oral diseases. AIM: To evaluate in inflammatory bowel disease patients the prevalence of sleep bruxism and its correlation with the presence of oral diseases, quality of sleep, and psychological disturbances. METHODS: Patients were consecutively recruited in our clinic and examined for temporomandibular disorders, dental enamel disorders, sleep bruxism, and recurrent aphthous stomatitis by two dentists. Patients also underwent Pittsburgh Sleep Quality Index and Beck Depression Inventory Scale questionnaires. RESULTS: 47 patients and 46 controls were included. Sleep bruxism and enamel wear disorders were more frequent in Crohn's disease patients when compared with ulcerative colitis patients and controls (p = 0.03 and p = 0.02, resp.). Among groups, no differences were noted for enamel hypoplasia, temporomandibular disorders, recurrent aphthous stomatitis, depression, and quality of sleep. We found a positive correlation between bruxism and temporomandibular disorders (Spearman 0.6, p < 0.001) and between bruxism and pathological sleep (Pittsburgh Sleep Quality Index > 5) (Spearman 0.3, p < 0.005). CONCLUSION: Bruxism and enamel wear disorders should be routinely searched in Crohn's disease patients. Moreover, the attention of healthcare givers to sleep disturbances should be addressed to all inflammatory bowel disease patients.

High risk of lower urinary tract symptoms in patients with irritable bowel syndrome.

BACKGROUND: The aim of the present study was to investigate the prevalence of urinary tract infection (UTI) and the risk of lower urinary tract symptoms (LUTS) in women with irritable bowel syndrome (IBS) (including each subtype: constipation, diarrhea, and mixed) compared to women in the general population. METHODS: Between January 2014 and December 2015, consecutive adult female patients diagnosed with IBS at the outpatient clinic of the University of Salerno and healthy women with regular bowel habits were enrolled in the study. At baseline, we checked for UTI with a dipstick test and questioned patients about the presence of LUTS in the previous 24 h. RESULTS: We enrolled 141 IBS patients and 91 healthy controls in the study. There was no difference in the prevalence of UTI between IBS patients and healthy controls (4.9 vs 3.3%, p = 0.5). When we excluded patients with UTI, we found a 2.79 higher risk of increased urinary frequency [odds ratio (OR) 2.79, 95% confidence interval (CI) 1.37-5.68], a 2.68 higher risk of urinary urgency (OR 2.68, 95% CI 1.04-6.91), and more than three times the risk of having dysuria (OR 3.25, 95% CI 1.06-9.97) in IBS women compared to healthy controls. The risk of having at least one urinary symptom was independent of IBS subtype and IBS severity. CONCLUSIONS: Our study shows that IBS women have a similar risk of UTI compared to healthy women even if they complain more of LUTS, independently of IBS subtype and severity.

Responses of Mytilus galloprovincialis hemocytes to environmental strains of Vibrio parahaemolyticus, Vibrio alginolyticus, Vibrio vulnificus.

Marine bivalves are exposed to different types of bacteria in the surrounding waters, in particular of the Vibrio genus. In the hemocytes of the mussel Mytilus spp. immune responses to different vibrios have been largely characterized. However, little information is available on the hemocyte responses to human pathogenic vibrios commonly detected in coastal waters and bivalve tissues that are involved in seafood-borne diseases. In this work, functional parameters of the hemocytes from the Mediterranean mussel M. galloprovincialis were evaluated in response to in vitro challenge with different vibrios isolated from environmental samples of the Adriatic sea (Italy): V. parahaemolyticus Conero, V. alginolyticus 1513 and V. vulnificus 509. V. parahaemolyticus ATCC 43996 was used for comparison. At the 50:1 bacteria hemocyte ratio, only V. parahaemolyticus strains induced significant lysosomal membrane destabilisation. Stimulation of extracellular lysozyme release, total ROS, O2- and NO production were observed, although to different extents and with distinct time courses for different vibrios, V. vulnificus 509 in particular. Further comparisons between V. parahaemolyticus Conero and V. vulnificus 509 showed that only the latter induced dysregulation of the phosphorylation state of p38 MAP Kinase and apoptotic processes. The results indicate that mussel hemocytes can mount an efficient immune response towards V. parahaemolyticus and V. alginolyticus strains, whereas V. vulnificus 509 may affect the hemocyte function. This is the first report on immune responses of mussels to local environmental isolates of human pathogenic vibrios. These data reinforce the hypothesis that Mytilus hemocytes show specific responses to different vibrio species and strains.

The risk of community-acquired pneumonia among 9803 patients with coeliac disease compared to the general population: a cohort study.

BACKGROUND: Patients with coeliac disease are considered as individuals for whom pneumococcal vaccination is advocated. AIM: To quantify the risk of community-acquired pneumonia among patients with coeliac disease, assessing whether vaccination against streptococcal pneumonia modified this risk. METHODS: We identified all patients with coeliac disease within the Clinical Practice Research Datalink linked with English Hospital Episodes Statistics between April 1997 and March 2011 and up to 10 controls per patient with coeliac disease frequency matched in 10-year age bands. Absolute rates of community-acquired pneumonia were calculated for patients with coeliac disease compared to controls stratified by vaccination status and time of diagnosis using Cox regression in terms of adjusted hazard ratios (HR). RESULTS: Among 9803 patients with coeliac disease and 101 755 controls, respectively, there were 179 and 1864 first community-acquired pneumonia events. Overall absolute rate of pneumonia was similar in patients with coeliac disease and controls: 3.42 and 3.12 per 1000 person-years respectively (HR 1.07, 95% CI 0.91-1.24). However, we found a 28% increased risk of pneumonia in coeliac disease unvaccinated subjects compared to unvaccinated controls (HR 1.28, 95% CI 1.02-1.60). This increased risk was limited to those younger than 65, was highest around the time of diagnosis and was maintained for more than 5 years after diagnosis. Only 26.6% underwent vaccination after their coeliac disease diagnosis. CONCLUSIONS: Unvaccinated patients with coeliac disease under the age of 65 have an excess risk of community-acquired pneumonia that was not found in vaccinated patients with coeliac disease. As only a minority of patients with coeliac disease are being vaccinated there is a missed opportunity to intervene to protect these patients from pneumonia.

Evidence for immunomodulation and apoptotic processes induced by cationic polystyrene nanoparticles in the hemocytes of the marine bivalve Mytilus.

Polymeric nanoparticles can reach the marine environment from different sources as weathering of plastic debris and nanowaste. Nevertheless, few data are available on their fate and impact on marine biota. Polystyrene nanoparticles (PS NPs) can be considered as a model for studying the effects of nanoplastics in marine organisms: recent data on amino-modified PS NPs (PS-NH2) toxicity in sea urchin embryos underlined that marine invertebrates can be biological targets of nanoplastics. Cationic PS NPs have been shown to be toxic to mammalian cells, where they can induce apoptotic processes; however, no information is available on their effects and mechanisms of action in the cells of marine organisms. In this work, the effects of 50 nm PS-NH2 were investigated in the hemocytes of the marine bivalve Mytilus galloprovincialis. Hemocytes were exposed to different concentrations (1, 5, 50 µg/ml) of PS-NH2 suspension in ASW. Clear signs of cytoxicity were evident only at the highest concentrations (50 µg/ml). On the other hand, a dose dependent decrease in phagocytic activity and increase in lysozyme activity were observed. PS-NH2 NPs also stimulated increase in extracellular ROS (reactive oxygen species) and NO (nitric oxide) production, with maximal effects at lower concentrations. Moreover, at the highest concentration tested, PS-NH2 NPs induced apoptotic process, as evaluated by Flow cytometry (Annexin V binding and mitochondrial parameters). The results demonstrate that in marine invertebrates the immune function can represent a significant target for PS-NPs. Moreover, in Mytilus hemocytes, PS-NH2 NPs can act through mechanisms similar to those observed in mammalian cells. Further research is necessary on specific mechanisms of toxicity and cellular uptake of nanoplastics in order to assess their impact on marine biota.

Interactive effects of nanoparticles with other contaminants in aquatic organisms: Friend or foe?

The increasing production and use of nanoparticles (NPs) will lead to their release into the aquatic environment, posing a potential threat to the health of aquatic organisms. Both in the water phase and in the sediments NPs could mix and interact with other pollutants, such as organic xenobiotics and heavy metals, leading to possible changes in their bioavailability/bioconcentration/toxicity. However, whether these interactive effects may lead to increased harmful effects in marine organisms is largely unknown. In this work, available data mainly obtained on carbon based NPs and n-TiO2, as examples of widespread NPs, in aquatic organisms are reviewed. Moreover, data are summarized on the interactive effects of n-TiO2 with 2,3,7,8-TCDD and Cd(2+), chosen as examples of common and persistent organic and inorganic contaminants, respectively, in the model marine bivalve Mytilus. The results reveal complex and often unexpected interactive responses of NPs with other pollutants, depending on type of contaminant and the endpoint measured, as well as differences in bioaccumulation. The results are discussed in relation with data obtained in freshwater organisms. Overall, information available so far indicate that interactive effects of NPs with other contaminants do not necessarily lead to increased toxicity or harmful effects in aquatic organisms.

Campylobacter jejuni cell lysates differently target mitochondria and lysosomes on HeLa cells.

Campylobacter jejuni is the most common cause of bacterial gastroenteritis in humans. The synthesis of cytolethal distending toxin appears essential in the infection process. In this work we evaluated the sequence of lethal events in HeLa cells exposed to cell lysates of two distinct strains, C. jejuni ATCC 33291 and C. jejuni ISS3. C. jejuni cell lysates (CCLys) were added to HeLa cell monolayers which were analysed to detect DNA content, death features, bcl-2 and p53 status, mitochondria/lysosomes network and finally, CD54 and CD59 alterations, compared to cell lysates of C. jejuni 11168H cdtA mutant. We found mitochondria and lysosomes differently targeted by these bacterial lysates. Death, consistent with apoptosis for C. jejuni ATCC 33291 lysate, occurred in a slow way (>48 h); concomitantly HeLa cells increase their endolysosomal compartment, as a consequence of toxin internalization besides a simultaneous and partial lysosomal destabilization. C. jejuni CCLys induces death in HeLa cells mainly via a caspase-dependent mechanism although a p53 lysosomal pathway (also caspase-independent) seems to appear in addition. In C. jejuni ISS3-treated cells, the p53-mediated oxidative degradation of mitochondrial components seems to be lost, inducing the deepest lysosomal alterations. Furthermore, CD59 considerably decreases, suggesting both a degradation or internalisation pathway. CCLys-treated HeLa cells increase CD54 expression on their surface, because of the action of lysate as its double feature of toxin and bacterial peptide. In conclusion, we revealed that C. jejuni CCLys-treated HeLa cells displayed different features, depending on the particular strain.

The kiwi fruit peptide kissper displays anti-inflammatory and anti-oxidant effects in in-vitro and ex-vivo human intestinal models.

Literature reports describe kiwi fruit as a food with significant effects on human health, including anti-oxidant and anti-inflammatory activity. Fresh fruit or raw kiwi fruit extracts have been used so far to investigate these effects, but the molecule(s) responsible for these health-promoting activities have not yet been identified. Kissper is a kiwi fruit peptide displaying pore-forming activity in synthetic lipid bilayers, the composition of which is similar to that found in intestinal cells. The objective of this study was to investigate the kissper influence on intestinal inflammation using cultured cells and ex-vivo tissues from healthy subjects and Crohn's disease (CD) patients. The anti-oxidant and anti-inflammatory properties of kissper were tested on Caco-2 cells and on the colonic mucosa from 23 patients with CD, by challenging with the lipopolysaccharide from Escherichia coli (EC-LPS) and monitoring the appropriate markers by Western blot and immunofluorescence. EC-LPS challenge determined an increase in the intracellular concentration of calcium and reactive oxygen species (ROS). The peptide kissper was highly effective in preventing the increase of LPS-induced ROS levels in both the Caco-2 cells and CD colonic mucosa. Moreover, it controls the calcium increase, p65-nuclear factor (NF)-kB induction and transglutaminase 2 (TG2) activation inflammatory response in Caco-2 cells and CD colonic mucosa. Kissper efficiently counteracts the oxidative stress and inflammatory response in valuable model systems consisting of intestinal cells and CD colonic mucosa. This study reports the first evidence supporting a possible correlation between some beneficial effects of kiwi fruit and a specific protein molecule rather than generic nutrients.

A pilot study on the effect of a symbiotic mixture in irritable bowel syndrome: an open-label, partially controlled, 6-month extension of a previously published trial.

BACKGROUND: In recent years, the efficacy of probiotics has received considerable attention in the treatment for irritable bowel syndrome (IBS). In this regard, a symbiotic mixture (Probinul(®)) has shown beneficial effects. The aim of this study was to extend the previously published 4-week randomized, double-blinded, placebo-controlled study of this symbiotic mixture. METHODS: This is an open-label prospective, partially controlled, 6-month extension period pilot study in which patients continued to receive the symbiotic mixture (Group 1) or were switched from placebo to symbiotic mixture (Group 2) using cyclic administration (last 2 weeks/month). The primary endpoints were the overall satisfactory relief of bloating and flatulence (assessed as proportions of responders). The secondary endpoints were evaluation of the symptom severity scores (bloating, flatulence, pain and urgency) and bowel function scores (frequency, consistency and incomplete evacuation). RESULTS: Twenty-six IBS patients completed the 6-month extension period (13 patients in Group 1 and 13 patients in Group 2). In the per-protocol analysis, the proportions of responders across time were not significantly different in the groups but in Group 2, there was an increased percentage of responders for flatulence (p = 0.07). In addition, the score of flatulence was reduced significantly during the 6-month treatment period in Group 2 (p < 0.05), while no other significant differences were detected. CONCLUSIONS: Treatment with this symbiotic mixture was associated with persistence of relief from flatulence or new reduction in flatulence in the present 6-month long extension study. These results need to be more comprehensively assessed in large, long-term, randomized, placebo-controlled studies.

Prevalence of eating disorders in adults with celiac disease.

Background. Symptoms of celiac disease negatively impact social activities and emotional state. Aim was to investigate the prevalence of altered eating behaviour in celiac patients. Methods. Celiac patients and controls completed a dietary interview and the Binge Eating Staircases, Eating Disorder Inventory (EDI-2), Eating Attitudes Test, Zung Self-Rating Depression Scale, State Trait Anxiety Inventory Forma Y (STAI-Y1 and STAI-Y2), and Symptom Check List (SCL-90). Results. One hundred celiac adults and 100 controls were not statistically different for gender, age, and physical activity. STAI-Y1 and STAI-Y2, Somatization, Interpersonal, Sensitivity, and Anxiety scores of the SLC-90 were higher in CD patients than controls. EDI-2 was different in pulse thinness, social insecurity, perfectionism, inadequacy, ascetisms, and interpersonal diffidence between CD and HC women, whilst only in interceptive awareness between CD and HC men. A higher EAT-26 score was associated with the CD group dependently with gastrointestinal symptoms. The EAT26 demonstrated association between indices of diet-related disorders in both CD and the feminine gender after controlling for anxiety and depression. Conclusion. CD itself and not gastrointestinal related symptoms or psychological factors may contribute pathological eating behavior in celiac adults. Eating disorders appear to be more frequent in young celiac women than in CD men and in HC.

Interactions between Mytilus galloprovincialis hemocytes and the bivalve pathogens Vibrio aestuarianus 01/032 and Vibrio splendidus LGP32.

Marine bivalves can accumulate large numbers of bacteria, in particular Vibrio species, whose persistence in bivalve tissues largely depends on their sensitivity to the bactericidal activity of circulating hemocytes and hemolymph soluble factors. The interactions between vibrios and hemolymph have been investigated, in particular in bivalve species susceptible to infection by certain Vibrio spp. and strains. In this work, the effects of two bivalve pathogens, Vibrio splendidus LGP32 (V.s.) and Vibrio aestuarianus 01/032 (V.a.), isolated from oyster mortality outbreaks, on the hemocytes of Mytilus galloprovincialis were investigated. In vitro, V.s., but not V.a., induced a dramatic decrease in lysosomal membrane stability-LMS in the hemocytes; both vibrios induced a moderate lysozyme release, with V.s. > V.a.. The V.s.-induced decrease in LMS was mediated by activation of PI-3Kinase, as shown by use of different kinase inhibitors. TEM analysis showed rapid internalization of both vibrios; however, V.s. lead to cellular and lysosomal damage and was able to survive within the hemocytes, whereas significant killing of V.a. was observed. In vivo, in mussels challenged with either vibrio and sampled at 6, 24 and 96 h post-injection, transient decreases in hemocyte LMS and progressive increases in serum lysozyme activity were observed, with V.s. > V.a.. Moreover, whereas V.a. was efficiently cleared from hemolymph, V.s. showed significant growth, that was maximal at 24 h p.i. when lowest LMS values were recorded in the hemocytes. Both vibrios also induced significant decreases in LMS in the digestive gland, again with V.s. > V.a.. The results indicate distinct interactions between mussel hemocytes and the two vibrio strains tested. The effects of V.s. may be due to the capacity of this strain to interfere with the signaling pathways involved in hemocyte function, thus escaping the bactericidal activity of the host cell, as observed for certain mammalian pathogens. Although V.s. is considered not pathogenic to Mytilus, this vibrio strain can affect the lysosomal function at the cellular and tissue level, thus leading to stressful conditions.

Role of gluten intake at the time of hepatitis B virus vaccination in the immune response of celiac patients.

Some reports have demonstrated an inadequate response to hepatitis B vaccination in patients affected by celiac disease. The aim of our study was to evaluate hepatitis B vaccination response in relation to gluten exposure status in patients with celiac disease. To measure the gluten exposure status at the time of vaccination, we considered three groups: group A (exposed to gluten), including patients vaccinated as 12-year-old adolescents (the celiac disease diagnosis was established after vaccination); group B (not exposed to gluten), including patients vaccinated as 12-year-old adolescents on a gluten-free diet at the time of vaccination; and group C (infants), including patients vaccinated at birth. The response of celiac patients to hepatitis B vaccination was compared to that of healthy subjects, i.e., those in the control group (group D). This study included 163 celiac patients (group A, 57 patients; group B, 46 patients; and group C, 60 patients) and 48 controls (group D). An inadequate response to hepatitis B immunization was present in 43.9% of patients in group A, 34.8% of patients in group B, 58.3% of patients in group C, and 8.3% of patients in group D (group A versus group D, P < 0.001; group B versus group D, P = 0.002; group C versus group D, P = 0.001) (no significant difference for group A versus group B and group A versus group C was evident). Our data suggest that gluten exposure does not influence the response to hepatitis B immunization and that the human leukocyte antigen probably plays the main immunological role in poor responses to hepatitis B-vaccinated celiac patients.

Colonic gas transit in patients with bloating: the effect of an electromechanical stimulator of the abdominal wall.

BACKGROUND: The aim of our study was to evaluate gas retention, abdominal symptoms and changes in girth circumference in females with bloating using an active or sham abdominal wall mechanical stimulation. METHODS: In 14 female patients, complaining of bloating (11 with irritable bowel syndrome and 3 with functional bloating according to the Rome III criteria) a gas mixture was continuously infused into the colon for 1 h (accommodation period). Abdominal perception and girth were measured. At the beginning of the 30-min period of free rectal gas evacuation (clearance period), an electromechanical device was positioned on the abdominal wall of all patients. The patients were randomly assigned to an active or a sham stimulation protocol group. Gas retention, perception and abdominal distension were measured at the end of the clearance period. RESULTS: All patients tolerated the volume (1,440 ml) of gas infused into the colon. Abdominal perception and girth measurements was similar in both groups during the accommodation period. At the end of the clearance, the perception score and the girth changes in the active and sham stimulation groups were similar (2.8 ± 2.0 vs. 1.4 ± 1.2, p = 0.2 and 4.9 ± 4.5 vs. 2.8 ± 2.3 mm, p = 0.3 active vs. sham, respectively). Furthermore, the mechanical stimulation of the abdominal wall did not significantly reduce gas retention (495 ± 101 ml vs. 566 ± 55, active vs. sham, p = 0.1). CONCLUSIONS: An external mechanical massage of the abdominal wall did not improve intestinal gas transit, abdominal perception and abdominal distension in our female patients complaining of functional bloating.

Increased risk of epilepsy in biopsy-verified celiac disease: a population-based cohort study.

OBJECTIVES: Celiac disease (CD) is associated with several neurologic disorders but it is unclear whether CD is associated with epilepsy. We therefore investigated whether biopsy-verified CD is associated with epilepsy. METHODS: Cohort study. Using biopsy report data from all Swedish pathology departments (n = 28), we identified individuals with CD who were diagnosed from 1969 to 2008 (Marsh 3: villous atrophy). Through Cox regression, we calculated hazard ratios (HRs) for epilepsy (defined as a diagnosis of epilepsy in the Swedish National Patient Register) in 28,885 individuals with CD and 143,166 controls matched for age, sex, calendar period, and county. RESULTS: Individuals with CD were at an increased risk of future epilepsy (HR = 1.42; 95% confidence interval [CI] = 1.24-1.62) (272 individuals with CD had a diagnosis of epilepsy vs an expected 192). The absolute risk of future epilepsy in patients with CD was 92/100,000 person-years (excess risk = 27/100,000 person-years). This risk increase was seen in all ages, including children with CD. The HR for having at least 2 interactions with health care due to epilepsy was 1.41 (95% CI = 1.19-1.66). When we restricted epilepsy to those with both a diagnosis of epilepsy and an independent record of antiepileptic drug prescriptions, CD was associated with a 1.43-fold increased risk of epilepsy (95% CI = 1.10-1.86). CONCLUSION: Individuals with CD seem to be at a moderately increased risk of epilepsy.

Moderately increased risk of urinary stone disease in patients with biopsy-verified coeliac disease.

BACKGROUND: Urinary stone disease is a mal-absorptive disorder that is a significant health problem because of its high prevalence and incidence. However, there are few population-based studies on the risk of urinary stone disease in patients with coeliac disease (CD). AIM: To examine the risk of urinary stone disease in CD. METHODS: Population-based cohort study. Using small intestinal biopsy report data from 1969 to 2008 obtained from all Swedish pathology departments (n = 28), we identified 28 735 patients with CD (equal to Marsh 3: villous atrophy). Patients were then matched for gender, age, county and calendar year to 142 177 reference individuals from the Swedish general population. We used Cox regression to estimate hazard ratios (HRs) for future urinary stone disease and conditional logistic regression to calculate odds ratios (ORs) for urinary stone disease before diagnosis of CD. Individuals with urinary stone disease were identified through the Swedish National Patient Register that contains data on inpatient care, outpatient care and day surgery. RESULTS: During follow-up, 314 individuals with CD and 1142 reference individuals developed urinary stone disease. This corresponded to a 27% increased risk of urinary stone disease in CD [95% confidence interval (CI) = 1.12-1.44]. CD patients had an absolute risk of urinary stone disease of 107/100 000 person-years (excess risk of 23/100 000). Risk estimates were similar in men and women, and did not differ according to age at CD diagnosis. Conditional logistic regression found that patients with CD were at a slightly increased risk also of prior urinary stone disease (OR = 1.19; 95% CI = 1.06-1.33). CONCLUSION: In this study, coeliac disease was associated with a moderately increased risk of urinary stone disease both before and after coeliac disease diagnosis.

Immunomodulation in Mytilus galloprovincialis by non-toxic doses of hexavalent chromium.

In aquatic organisms, the immune function can be affected by exposure to environmental pollutants, including heavy metals. In vertebrate systems, different forms of Cr have been shown induce either immunostimulatory or immunosuppressive processes. Hexavalent Cr, Cr(VI), is an important contaminant released from both domestic and industrial effluents, and the predominant chemical form of the metal in aquatic ecosystems. In this work, the in vitro and in vivo effects of Cr(VI) on immune parameters of the marine bivalve Mytilus galloprovincialis were evaluated. Hemocyte incubation with different concentrations of Cr(VI) (0.1-1-10-100 µM) induced a dose-dependent decrease in lysosomal membrane stability (LMS). Decreases in extracellular lysozyme release and phagocytic activity were also observed, with stronger effects at lower metal concentrations. On the other hand, in these conditions, Cr(VI) stimulated extracellular superoxide production and nitrite accumulation. The effects of Cr(VI) were also evaluated in mussels exposed to the metal (0.1-1-10 µg L(-1), corresponding to nanomolar concentrations) for 96 h. Decreases in hemocyte LMS values and in serum lysozyme activity were observed with increasing metal concentrations. Decreased phagocytic activity and increased NO production were recorded, with stronger effects at lower concentrations. In these conditions, decreased Total Hemocyte Counts (THC), but no necrotic/apoptotic processes were observed. Moreover, Cr(VI) at both 0.1 and 1 µg L(-1) seemed to induce significant changes in transcription of immune genes (lysozyme, Mytilin C, Myticin B, defensin, MgC1q), of the serotonin receptor (5-HTR) and of the stress protein HSP70, whereas that of the anti-apoptotic gene p53 was unaffected. Overall, the results indicate that exposure to non-toxic, environmentally relevant concentrations of Cr(VI) can modulate functional and molecular immune parameters in M. galloprovincialis.