Vitamin E and vitamin E acetate absorption from self-assembly systems under pancreas insufficiency conditions.

We determined the bioavailability of vitamin E from self-assembly structures in patients with diagnosed chronic pancreas insufficiency. Vitamin E solubilized in dispersed inverted bicontinuous cubic phase and in micellar formulation was delivered directly to the small intestine by tube-feeding. A cross-over study with randomization of 6 subjects and 2 treatments including a combined dose of 18 mg (27 IU) of vitamin E (RRR-[5,7-methyl-((2)H6)]-α-tocopherol) and 27 mg (27 IU) vitamin E acetate (RRR-[5-methyl-(2)H3]-α-tocopheryl acetate) was applied over a time period of 1 h. Plasma samples were collected for 56 h and analyzed by liquid chromatography-mass spectrometry. Appearance of labeled tocopherols originating from the treatment started at 25 h and reached Cmax (0.6-4.6 µM depending on subject) in the 7-9 h window. From the Tmax onwards, both forms of tocopherols diminished slowly to 30-50% of their maxima within 56 h. Strong inter-individual variation was observed in the plasma appearance curves (relative standard deviation varied between 38-45%). No significant discrimination was found between the absorption of free or acetylated forms of deuterated α-tocopherol confirming that application of acetylated α-tocopherol provides the same bioavailability as free α-tocopherol. This observation is valid in both dispersed inverted bicontinuous cubic phase and micellar formulations. Furthermore, since the area-under-the-curve values from cubic phase and from micellar formulations are similar, the cubic phase formulation could represent an alternative delivery system for lipophilic micronutrients in conditions or studies where polysorbate-based micelles cannot be generated.

Clinical significance of small bowel manometry patterns suggestive of intestinal obstruction.

INTRODUCTION: Minute rhythm and prolonged simultaneous contractions are patterns of postprandial small bowel contractile activity that historically have been considered as suggestive of mechanical intestinal obstruction; however, these patterns have been also encountered in patients with motility-like symptoms in the absence of bowel obstruction. The objective of this study was to determine the current diagnostic outcome of patients with these intestinal manometry patterns. METHODS: Retrospective study of patients with chronic digestive symptoms evaluated by intestinal manometry at our center between 2010 and 2018. RESULTS: The minute rhythm (MRP) or prolonged simultaneous contractions (PSC) postprandial patterns were detected in 61 of 488 patients (55 MRP and 6 PSC). Clinical work-up detected a previously non-diagnosed partial mechanical obstruction of the distal intestine in 10 (16%) and a systemic disorder causing intestinal neuropathy in 32 (53%). In the remaining 19 patients (31%, all with MRP), the origin of the contractile pattern was undetermined, but in 16, substantial fecal retention was detected within 7 days of the manometric procedure by abdominal imaging, and in 6 of them colonic cleansing completely normalized intestinal motility on a second manometry performed within 39 ± 30 days. CONCLUSION AND INFERENCE: Currently, the most frequent origin of MRP and PSC encountered on small bowel manometry is intestinal neuropathy, while a previously undetected mechanical obstruction is rare. Still, in a substantial proportion of patients, no underlying disease can be identified, and in them, colonic fecal retention might play a role, because in a subgroup of these patients, manometry normalized after colonic cleansing. Hence, colonic preparation may be considered prior to intestinal manometry.

Metabotyping of biofluids reveals stress-based differences in gut permeability in healthy individuals.

Life stress promotes gut dysfunction, but underlying biochemical events are not well-understood. In the present study, we describe the metabolic events associated with background stress and its potential influence on the response to novel incoming stress stimulus in healthy subjects. A 15 min cold pain test was carried out in healthy men and women stratified according to low (LS; n = 21) and moderate background stress (MS; n = 9) during jejunal segmental perfusion. Cold pain induced a stronger psychological response in MS compared to LS subjects, but similar increases in heart rate and blood pressure. Urine and plasma were analyzed using 1H NMR-based metabonomics. Basal stress levels were imprinted in the metabolic profiles indicating different energy and lipid homeostasis. Cold pain increased gut permeability, as determined by mannitol and xylose levels, the response being greater in LS subjects. Moreover, the rate of plasma clearance of mannitol and xylose was dependent on background stress level and gender. In addition, cold pain modulated the levels of circulating ketone bodies, Krebs's cycle intermediates, glucose, and the glucogenic alanine and lactate, which brings further evidence of an alteration of energy homeostasis. Therefore, unravelling life stress with metabonomics may provide a system biology basis for the clinical management and therapeutic surveillance of gut health and disorders.

Maladaptive intestinal epithelial responses to life stress may predispose healthy women to gut mucosal inflammation.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS), a highly prevalent disorder among women, has been associated with life stress, but the peripheral mechanisms involved remain largely unexplored. METHODS: A 20-cm jejunal segment perfusion was performed in 2 groups of young healthy women, equilibrated by menstrual phase, experiencing either low (LS; n = 13) or moderate background stress (MS; n = 11). Intestinal effluents were collected every 15 minutes, for 30 minutes under basal conditions, and for 1 hour after cold pain stress. Cardiovascular and psychological response, changes in circulating stress and gonadal hormones, and epithelial function (net water flux, albumin output and luminal release of tryptase and alpha-defensins) to cold stress were determined. RESULTS: Cold pain induced a psychological response stronger in the MS than in the LS group, but similar increases in heart rate, blood pressure, adrenocorticotrophic hormone, and cortisol, whereas estradiol and progesterone remained unaltered. Notably, the jejunal epithelium of MS females showed a chloride-related decrease in peak secretory response (Delta[15-0 minutes]: LS, 97.5 [68.4-135.0]; MS, 48.8 [36.6-65.0] microL/min/cm; P < .001) combined with a marked enhancement of albumin permeability (LS(AUC), 6.35 [0.9-9.6]; MS(AUC), 13.97 [8.3-23.1] mg/60 min; P = .008) after cold stress. Epithelial response in both groups was associated with similar increases in luminal tryptase and alpha-defensins release. CONCLUSIONS: Increased exposure to life events determines a defective jejunal epithelial response to incoming stimuli. This abnormal response may represent an initial step in the development of prolonged mucosal dysfunction, a finding that could be linked to enhanced susceptibility for IBS.

Abdominal accommodation: a coordinated adaptation of the abdominal wall to its content.

BACKGROUND AND AIM: We previously showed that colonic gas infusion increases the girth and modifies the muscular activity of the anterior abdominal wall. We hypothesized that abdominal accommodation to volume loads is an active process instrumented by the coordinated activity of the anterior wall and the diaphragm. METHODS: To increase intraabdominal volume in healthy subjects, a gas was infused into the colon (1.44 L in 1 h) while measuring girth (by tape measure) and electromyography (EMG) activity of the anterior wall (via four pairs of surface electrodes) and the diaphragm (via six ring electrodes over an esophageal tube in the hiatus). After preliminary feasibility studies (N = 12), postural activity (N = 6) and responses to colonic gas loads, both with the trunk erect (N = 8) and in supine position (N = 8), were studied. A morphometric analysis was performed by computed tomography, image analysis (N = 8). RESULTS: In the erect position, anterior wall tone was higher and diaphragmatic tone was lower than in the supine position. With the trunk erect, gas infusion induced diaphragmatic relaxation (by 21 +/- 3%; P < 0.05) and anterior wall contraction (16 +/- 4% EMG increment; P < 0.05). By contrast, in the supine position, it induced diaphragmatic contraction (15 +/- 6%, P < 0.05), while the anterior wall, in the absence of postural tone, showed no change (3 +/- 2%, NS). Gas infusion was associated with girth increase (7.3 +/- 1.0 mm with the trunk erect and 8.6 +/- 1.4 mm in the supine position) and diaphragmatic ascent (17.6 +/- 5.2 mm; P < 0.05). CONCLUSION: The degree of abdominal distension produced by intraabdominal volume increments results from posture-related abdomino-phrenic muscular responses.

The gut microbiota predispose to the pathophysiology of acute postradiotherapy diarrhea.

INTRODUCTION: Severe diarrhea may complicate pelvic radiotherapy and force interruption of treatment. As there is no current clinical or experimental information on the role of the gut microbiota in this pathogenesis, we conducted a pilot observational study on the fecal microbiota in patients receiving pelvic radiotherapy. METHODS: The study involved 10 patients who underwent 5 wk of radiotherapy for abdominal tumors and 5 controls. Four fecal samples were collected from each individual: before, during, at the end, and 2 wk after treatment. Following the amplification of the bacterial 16S rRNA gene from the samples, DNA fingerprinting and cloning-sequencing techniques were used to determine their microbial profile and composition, respectively. RESULTS: Six patients suffered acute postradiotherapy diarrhea and 4 did not. In patients without diarrhea, as well as in healthy volunteers, microbial diversity was stable over a period of 7 wk. However, patients exhibiting diarrhea showed a progressive modification in their microbial diversity. A radical drop in similarity index was observed at the end (P= 0.026) and still 2 wk after radiotherapy (P= 0.014). Interestingly, cluster analysis of the microbial profile in the first sample (S1) (collected before radiotherapy) displayed a dendogram where patients that presented diarrhea clustered separately from those that did not develop diarrhea after radiotherapy. Moreover, sequence analysis of dominant bacteria in the S1 sample confirmed differences between the diarrhea and nondiarrhea groups. DISCUSSION: In this set of patients, susceptibility or protection against diarrhea after radiotherapy could be linked to different initial microbial colonization.

[Epidemiology of inflammatory bowel disease in the elderly]. / Epidemiología de la enfermedad inflamatoria intestinal en el paciente de edad avanzada.

INTRODUCTION: Inflammatory bowel disease has classically been considered a disorder with onset in young people. However, between 5 and 15% of patients are diagnosed when aged more than 60 years old. Epidemiological studies comparing these two age groups are controversial and consequently new studies are required to define the characteristics in each group. OBJECTIVES: To determine the epidemiological characteristics specific to Crohn's disease and ulcerative colitis in the elderly and to compare these characteristics with the form of presentation in young people in Spain. METHOD: We performed a case-control, descriptive study. Patients with inflammatory bowel disease registered in the database of the Crohn-Colitis Unit were included. The patients were stratified in two groups according to age at symptom onset: the first group consisted of patients with onset at age 60 years or above and the second group was a control group consisting of patients aged less than 60 years old. The control group was composed of two patients for each case matched by sex and diagnosis. RESULTS: Thirty-three cases aged more than 60 years old (4.1%) were included, eight with Crohn's disease and 25 with ulcerative colitis. The control group included 66 patients (16 with Crohn's disease and 50 with ulcerative colitis). Statistically significant differences were observed between the two groups both in the form of presentation (tenesmus and occlusive symptoms were more frequent and abdominal pain was less frequent in the group aged more than 60 years than in the control group) and in treatment response (corticosteroid dependency and refractoriness and requirement for immunosuppressive treatment were more frequent in the elderly). CONCLUSION: The results of the present study suggest that there are epidemiological differences in inflammatory bowel disease among the elderly, notably a lower frequency of abdominal pain and a lower rate of refractoriness to steroid treatment.

Functional neuromuscular impairment in severe intestinal dysmotility.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) and enteric dysmotility (ED) are severe intestinal motility disorders usually associated with underlying neuromuscular abnormalities. OBJECTIVE: To evaluate the in vitro neuromuscular function of patients with severe intestinal motility disorders. METHODS: Full-thickness intestinal biopsies (16 jejunum and 3 ileum) obtained from patients with CIPO (n = 10) and ED (n = 9) were studied using muscle bath and microelectrode techniques. Control samples (n = 6 ileum and n = 6 jejunum) were used to establish the range of normality. KEY RESULTS: Fourteen parameters were defined to assess muscle contractility and nerve-muscle interaction: five to evaluate smooth muscle and interstitial cells of Cajal (ICC) and nine to evaluate inhibitory neuromuscular transmission. For each sample, a parameter was scored 0 if the value was inside the normal range or a value of 1 if it was outside. Patients' samples (CIPO/ED) had more abnormal parameters than controls (P < 0.001 for both jejunum and ileum). Functional abnormalities were found to be heterogeneous. The most prevalent abnormality was a decreased purinergic neuromuscular transmission, which was detected in 43.8% of jejunal samples. CONCLUSIONS AND INFERENCES: Abnormalities of neuromuscular intestinal function are detected in vitro in severe intestinal dysmotility. However, consistent with the heterogeneity of the disease pathophysiology, functional impairment cannot be attributed to a single mechanism. Specifically, defects of purinergic neuromuscular transmission may have an important role in motility disorders of the gastrointestinal tract.

Sustained improvement of health-related quality of life in Crohn's disease patients treated with infliximab and azathioprine for 4 years.

BACKGROUND: Infliximab induces remission and improves the health-related quality of life (HRQOL) of patients with refractory or fistulous Crohn's disease (CD). However, little information is available as to whether its effect on HRQOL is sustained over time. The objective was to measure the HRQOL of CD patients in long-term clinical remission. METHODS: Prospective, observational study was undertaken in patients with CD in infliximab-induced clinical remission (Harvey index <3) for at least 6 months, and receiving long-term infliximab and azathioprine maintenance therapy. Patients were followed for 4 years or until clinical relapse (Harvey index >3). HRQOL was assessed annually using the validated Spanish version of the disease-specific 36-item Inflammatory Bowel Disease Questionnaire (IBDQ-36) and the EuroQol-5D. RESULTS: Forty-nine patients with CD in stable clinical remission were included at baseline. At 12 months, n = 42 patients remained in remission, at 24 months n = 32 patients, at 36 months n = 13, and in the last visit at 48 months 6 patients remained in clinical remission. The overall score on the IBDQ-36 remained unchanged in patients with stable, inactive CD (median overall score of 6.1 at baseline and 6.5 at 4 years). Scores on all 5 dimensions of the IBDQ-36 remained unchanged over the study period in stable patients. Patients in remission scored highly on the preference value ratings of the EuroQol-5D (scores of 1.0) and remained unchanged in patients who remained in remission. CONCLUSIONS: Sustained clinical remission of CD achieved with maintenance treatment maintains HRQOL over long-term follow-up.

Targeting mast cells in the treatment of functional gastrointestinal disorders.

Enhanced knowledge of the pathophysiological basis of functional gastrointestinal disorders indicates that low-grade mucosal inflammation and mast cell hyperplasia are common findings. Mast cells are multipotent and mucosa-dwelling residents are uniquely located to communicate with host immune and nervous supersystems and with the gut microflora to provide tight microenvironmental conditions. Maintenance of homeostasis within this integrated defense system is crucial for symbiotic health, whereas breakdown of that balance might lead to uncontrolled mucosal and systemic inflammation. Numerous advances have recently emerged in the understanding of regulatory mechanisms of mast cell activation, development and homing to mucosal surfaces, as well as of the role of mast cells in key steps of mucosal inflammation. Such observations have stimulated the development of candidate drugs, such as tryptase or Syk inhibitors, that might be useful for the treatment of gastrointestinal functional disorders.

Induction of colonic transmural inflammation by Bacteroides fragilis: implication of matrix metalloproteinases.

BACKGROUND: Commensal bacteria are implicated in the pathophysiology of intestinal inflammation, but the precise pathogenetic mechanisms are not known. We hypothesized that Bacteroides fragilis-produced metalloproteinases (MMPs) are responsible for bacterial migration through the intestinal wall and transmural inflammation. AIM: To investigate the role of bacterial-MMP activity in an experimental model of colitis induced by the intramural injection of bacteria. METHODS: Suspensions of viable B. fragilis or Escherichia coli were injected into the colonic wall, and the effect of the MMP inhibitor (phenantroline) on histologic lesion scores was tested. MMP activity in bacterial suspensions was measured by azocoll assay. RESULTS: The inoculation with B. fragilis induced chronic inflammatory lesions that were preferentially located in the subserosa, whereas inoculation with E. coli induced acute-type inflammatory reactions, evenly distributed in both the submucosa and subserosa. Treatment with phenantroline significantly decreased subserosal lesion scores in rats inoculated with B. fragilis, but not in rats inoculated with E. coli. Bacterial suspensions of B. fragilis showed MMP activity, but E. coli suspensions did not. Sonication of B. fragilis reduced MMP activity and virulence to induce serosal lesions. CONCLUSION: Our data suggest that bacterial MMPs may be implicated in the serosal migration of B. fragilis and in the induction of transmural inflammation.

Increased plasma fibrinolytic activity in bleeding gastrointestinal angiodysplasia.

OBJECTIVE: Gastrointestinal angiodysplasia is a major cause of recurrent bleeding. Haemostatic abnormalities have been implicated in the haemorrhage from these common vascular lesions but their precise contribution remains to be established. Our aim was to investigate whether bleeding angiodysplasia is associated with any specific coagulation disorder. METHODS: Clinical features and blood samples were prospectively obtained from 21 patients with bleeding gastrointestinal angiodysplasia 3 months after the last episode of haemorrhage. Plasma levels of von Willebrand factor, D-dimer, plasminogen activator inhibitor type 1 (PAI-1), tissue-plasminogen activator activity, tissue factor pathway inhibitor and activated factor VII (FVIIa-rTF) were measured. A group of 14 patients with bleeding duodenal ulcer were similarly studied as controls. RESULTS: Mean plasma von Willebrand factor levels were higher in angiodysplasia patients (208+/-12%) than in controls (143+/-11%) (P<0.05). D-dimer levels (661+/-80 ng/ml) and tissue-plasminogen activator activity levels (2.04+/-0.14 IU/ml) were also higher than in controls: 395+/-99 ng/ml and 1.6+/-0.1 IU/ml, respectively (P<0.05), whereas levels of PAI-1, FVIIa-rTF and tissue factor pathway inhibitor were similar in both groups. However, PAI-1 levels (31.5+/-11 ng/ml) were lower in high-bleeding-rate angiodysplasia (more than two bleeding episodes/year) than in low-bleeding-rate angiodysplasia (< or = 2 bleeding episodes/year) (PAI-1 47+/-14 ng/ml) (P<0.05). In a multivariate regression analysis, the plasma level of PAI-1 was a predictor of haemorrhage from angiodysplasia (P<0.05). CONCLUSIONS: Increased plasma fibrinolytic activity may contribute to bleeding from angiodysplasia. Low plasma PAI-1 levels constitute a risk factor for bleeding tendency in patients with angiodysplasia.

Assessment of rectocolonic morphology and function in patients with Chagas disease in Barcelona (Spain).

The aim of this study was to determine the relationship between colonic symptoms, radiological abnormalities, and anorectal dysfunction in patients with Chagas disease. We performed a cross-sectional study of untreated patients diagnosed with Chagas disease. All patients were evaluated clinically (by a questionnaire for colonic symptoms based on Rome III criteria) and underwent a barium enema and anorectal manometry. A control group of patients with functional constipation and without Chagas disease was included in the study. Overall, 69 patients were included in the study: 42 patients were asymptomatic and 27 patients had abdominal symptoms according to Rome III criteria. Anorectal manometry showed a higher proportion of abnormalities in symptomatic patients than in asymptomatic ones (73% versus 21%, respectively; P < 0.0001). Megarectum was detected in a similar proportion in the different subgroups regardless of the presence of symptoms or abnormalities in anorectal functions. Among non-Chagas disease patients with functional constipation, 90% had an abnormal anorectal manometry study. Patients with Chagas disease present a high proportion of constipation with dyssynergic defecation in anorectal manometry but a low prevalence of impaired rectoanal inhibitory reflex, although these abnormalities may be nonspecific for Chagas disease. The presence of megarectum is a nonspecific finding.

Achalasia treatment in the elderly: is botulinum toxin injection the best option?

BACKGROUND: Achalasia treatment in elderly patients is a matter of controversy. Botulinum toxin injection has been proposed as the best option in this group of patients as it is a safe procedure. However, concern persists regarding its short-term effect. AIMS: To analyse the clinical and economic effectiveness of botulinum toxin injection in the treatment of achalasia patients who are elderly. METHODS: Seventeen consecutive achalasia patients older than 65 years were treated with 80 units of botulinum toxin. Clinical follow-up at 1, 6 and 12 months was performed. Control manometry when symptoms recurred was carried out. Results were compared with those of an historical control group of 16 achalasia patients also older than 65 years and who had been treated with endoscopic dilation. The costs of both procedures were compared. RESULTS: Twenty-nine botulinum toxin injections were performed in the 17 patients of the botulinum toxin group (follow-up, 12-36 months). In the dilation group only two patients had to be retreated (follow-up, 12-108 months). No major complications were observed in either group. The average duration of symptom alleviation was 48 +/- 33 months for endoscopic dilation and 13.8 +/- 9.5 months for botulinum toxin injection. Maintaining a patient free of symptoms cost E348.31 per year for botulinum toxin injection, whilst if endoscopic dilation was chosen the cost was only E117.47 per year. CONCLUSIONS: The effect of botulinum toxin injections wanes with time in elderly patients, necessitating repeated injections to keep the patients symptom-free. Due to the required repeated injections this procedure is more expensive than endoscopic dilation.

Effect of short-term octreotide therapy and total parenteral nutrition on the development of biliary sludge and lithiasis.

BACKGROUND/AIMS: Both total parenteral nutrition and long-term octreotide treatment (> 2 months) may induce biliary sludge and lithiasis. However, the lithogenic capacity of the combination of the two treatments in the short-term is unknown. This study was undertaken to evaluate the lithogenic capacity of short-term octreotide treatment (< 1 month) in patients with acute pancreatitis who are also receiving total parenteral nutrition, and to determine the evolution of patients who develop biliary sludge and/or lithiasis. METHODOLOGY: Thirty patients with acute pancreatitis were studied (21 males, 9 females; average age: 38). All patients received total parenteral nutrition and analgesics. In a double-blind random manner, 15 patients were treated with a continuous subcutaneous administration of octreotide (200 micrograms/8 h) and a further 15 patients received placebo. Biliary sludge and/or lithiasis were examined by ultrasonography. An echographic examination of the gallbladder was performed every seven days while the patients were in hospital. They were followed up every month, when another ultrasound of the gallbladder was carried out. RESULTS: Sixteen patients (53%) developed sludge: ten (67%) from the octreotide group and six (33%) from the placebo group (P = 0.29). Two of the patients from the octreotide group had microlithiasis (P = 0.34) and a cholecystectomy was required. In the other 14 patients, sludge had disappeared by the time of the check-up performed one month after discharge. CONCLUSIONS: Short-term octreotide treatment does not increase the risk of developing biliary sludge and/or lithiasis in patients also receiving total parenteral nutrition. Biliary sludge formed during total parenteral nutrition and short-term octreotide therapy may disappear when patients begin oral intake. Therefore, preventive measures are not required.

[The Crohn-Colitis care unit: analysis of the first 3 years of activity]. / La Unidad de Atención Crohn-Colitis: 3 años de actividad.

OBJECTIVE: To assess the activity of the Crohn-Colitis Care Unit (CCCU) and of its web site: http://www.ua-cc.org MATERIAL AND METHOD: The CCCU is a unit for the education and health promotion of patients with inflammatory bowel disease and their immediate circle. It includes a coordination center with a multidisciplinary team that manages patients' requests. The main means of contact is through telephone and the Web. RESULTS: After 3 years, there are 956 users registered in the CCCU, of which 87% are patients who generated more than 4,500 consultations on multiple topics. Telephone consultations account for 67% of all consultations and there are 500 users registered in the Web. CONCLUSIONS: The preliminary results suggest that the integral approach of the CCCU and its web site have had a significant impact on patients with inflammatory bowel disease.

Chronic psychosocial stress induces reversible mitochondrial damage and corticotropin-releasing factor receptor type-1 upregulation in the rat intestine and IBS-like gut dysfunction.

The association between psychological and environmental stress with functional gastrointestinal disorders, especially irritable bowel syndrome (IBS), is well established. However, the underlying pathogenic mechanisms remain unknown. We aimed to probe chronic psychosocial stress as a primary inducer of intestinal dysfunction and investigate corticotropin-releasing factor (CRF) signaling and mitochondrial damage as key contributors to the stress-mediated effects. Wistar-Kyoto rats were submitted to crowding stress (CS; 8 rats/cage) or sham-crowding stress (SC; 2 rats/cage) for up to 15 consecutive days. Hypothalamic-pituitary-adrenal (HPA) axis activity was evaluated. Intestinal tissues were obtained 1h, 1, 7, or 30 days after stress exposure, to assess neutrophil infiltration, epithelial ion transport, mitochondrial function, and CRF receptors expression. Colonic response to CRF (10 µg/kg i.p.) and hyperalgesia were evaluated after ending stress exposure. Chronic psychosocial stress activated HPA axis and induced reversible intestinal mucosal inflammation. Epithelial permeability and conductance were increased in CS rats, effect that lasted for up to 7 days after stress cessation. Visceral hypersensitivity persisted for up to 30 days post stress. Abnormal colonic response to exogenous CRF lasted for up to 7 days after stress. Mitochondrial activity was disturbed throughout the intestine, although mitochondrial response to CRF was preserved. Colonic expression of CRF receptor type-1 was increased in CS rats, and negatively correlated with body weight gain. In conclusion, chronic psychosocial stress triggers reversible inflammation, persistent epithelial dysfunction, and colonic hyperalgesia. These findings support crowding stress as a suitable animal model to unravel the complex pathophysiology underlying to common human intestinal stress-related disorders, such as IBS.

Validation of the Spanish version of a questionnaire to measure quality of care through the eyes of patients with inflammatory bowel disease (QUOTE-IBD).

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic immunoinflammatory diseases that place a considerable burden on patients, their families, and society. Quality of care plays an important role for patients. A questionnaire to measure quality of care through the eyes of patients with inflammatory bowel disease (QUOTE-IBD) has been designed and validated specifically for the English language and culture. The objective was to translate the QUOTE-IBD into Spanish and to determine its validity in patients with IBD. METHODS: This is a prospective study in 2 phases: first, translation and validation of the Spanish QUOTE-IBD. Translation was based on the validated QUOTE-IBD. Second, once the complete translation was finished, comprehension of the items was assessed with a specific questionnaire in a reduced number of patients. Criterion validity was assessed with the Pearson's correlation coefficient between scores of the QUOTE-IBD and visual analog scales (VAS). In order to analyze the reproducibility of the Spanish QUOTE-IBD, the questionnaire was completed by stable patients twice, with a span of time of at least 4 weeks. RESULTS: A total of 103 patients (CD: 61, UC: 42) were included in the study. Pearson's correlation coefficient between total care Spanish QUOTE-IBD and VAS of health care items was 0.34 (P < 0.001). Correlations among all 6 care dimensions score of Spanish QUOTE-IBD and VAS were statistically significant (P < 0.01). Results of first and second administration of total care and dimensional care scores of Spanish QUOTE-IBD in 46 stable patients were not different. CONCLUSIONS: The Spanish QUOTE-IBD has proved to be a valid instrument to measure the quality of health care for patients with CD and UC.

Tocotrienols induce apoptosis and autophagy in rat pancreatic stellate cells through the mitochondrial death pathway.

BACKGROUND & AIMS: Selective removal of activated pancreatic stellate cells (PSCs) through induction of their own programmed death is a goal of therapeutic interest in patients with chronic pancreatitis. Here, we investigated the effects of tocotrienols on PSC death outcomes. METHODS: Activated and quiescent PSCs and acinar cells from rat pancreas were treated with vitamin E derivatives alpha-tocopherol; individual alpha-, beta-, gamma-, and delta-tocotrienols; and a tocotrienol rich fraction (TRF) from palm oil. RESULTS: TRF, but not alpha-tocopherol, reduced viability of activated PSC by setting up a full death program, independent of cell cycle regulation. Activated PSCs died both through apoptosis, as indicated by increased DNA fragmentation and caspase activation, and through autophagy, as denoted by the formation of autophagic vacuoles and LC3-II accumulation. In contrast to alpha-tocopherol, TRF caused an intense and sustained mitochondrial membrane depolarization and extensive cytochrome c release. Caspase inhibition with zVAD-fmk suppressed TRF-induced apoptosis but enhanced autophagy. However, mitochondrial permeability transition pore blockade with cyclosporin A completely abolished the deadly effects of TRF. beta-, gamma-, and delta-tocotrienol, but not alpha-tocotrienol nor alpha-tocopherol, reproduced TRF actions on activated PSCs. TRF death induction was restricted to activated PSCs because it did not cause apoptosis either in quiescent PSCs or in acinar cells. CONCLUSIONS: Tocotrienols selectively trigger activated pancreatic stellate cell death by targeting the mitochondrial permeability transition pore. Our findings unveil a novel potential for tocotrienols to ameliorate the fibrogenesis associated with chronic pancreatitis.