Habitual Caffeine Use is Associated with Heightened Cortisol Reactivity to Lab-Based Stress in Two Samples.

OBJECTIVE: Habitual caffeine consumption protects against depression, but through unclear mechanisms. Although habitual caffeine use predicts cortisol release to other acute stressors (e.g., exercise), this is less examined with lab-based psychosocial stress in healthy adults. Further, caffeine-induced cortisol increases may mask theory-predicted cortisol blunting to robust stress in people with elevated depression risk. In two samples, we tested whether acute (same-day) and habitual caffeine use would predict greater cortisol reactivity to lab-based stress, and whether caffeine would "mask" the effect of a depression risk factor, trait rumination, on blunted cortisol reactivity. METHOD: In Sample 1, N = 128 emerging adults completed one of three Trier Social Stress Test conditions: non-evaluative Control, ambiguously evaluative Intermediate, or explicit Negative Evaluative. In Sample 2, N = 148 emerging adults completed either a Control or Negative Evaluative condition. RESULTS: In both samples, multilevel growth curve modeling indicated habitual ( t = -1.99, p = .048; t = -2.73, p = .007, Samples 1 and 2 respectively), but not acute caffeine use predicted heightened cortisol reactivity as a function of condition. In Sample 1, the relationship between condition, rumination, and blunted cortisol was evident only in caffeine non-users, which differed from users ( t = 2.82, p = .005), but in Sample 2 the predicted blunting pattern was evident regardless of caffeine use. CONCLUSION: This provides evidence that habitual caffeine use is associated with greater cortisol release under psychosocial lab-based stress and may mask the influence of psychosocial variables; future research should examine whether habitual caffeine-induced cortisol release has behaviorally activating effects that protect against depression.

Use of a proline-specific endopeptidase to reintroduce gluten in patients with non-coeliac gluten sensitivity: A randomized trial.

BACKGROUND: A gluten-free diet (GFD) is the main therapy for non-coeliac gluten sensitivity (NCGS). However, the availability of novel enzymes with the ability to digest gluten could represent a therapeutic opportunity for NCGS patients to avoid a GFD. AIMS: To evaluate the controlled reintroduction of gluten with or without the endopeptidase P1016 in NCGS patients. METHODS: This is a randomized, double-blind, placebo-controlled monocentric study, Registered under ClinicalTrials.gov Identifier no. NCT01864993. Gluten was reintroduced incrementally over a 3-week period under nutritional control. NCGS patients were randomized into two groups and administered P1016 or placebo during gluten reintroduction. We evaluated symptoms (visual analogue scale, VAS), quality of life (SF-36) and mental health symptoms (SCL-90) on a weekly basis. RESULTS: We enrolled a total 23 patients who were allocated to a placebo group (n = 11, age 38.4 ± 2.9) or an intervention group (n = 12, age 39.5 ± 3.1). No effect of P1016 on symptoms was found. During gluten reintroduction, patients reported a significant increase in abdominal pain and a worsening of stool consistency. Furthermore, no differences were found between the groups regarding SCL-90 and SF-36 scores. CONCLUSIONS: Our results demonstrate a lack of effect of P1016 in the management of NCGS patients and the possible reintroduction of gluten.

Are the dietary habits of treated individuals with celiac disease adherent to a Mediterranean diet?

BACKGROUND AND AIMS: The only treatment for celiac disease (CD) is strict, lifelong adherence to a gluten-free (GF) diet. To date, there are contrasting data concerning the nutritional adequacy of GF products and diet. There have been no studies that have assessed the adherence of individuals with CD to a Mediterranean diet (MD), a protective dietary regimen against major non-communicable diseases (NCDs). Therefore, we examined the adherence to an MD of a group of Italian individuals with CD and compared it with that of a healthy control group. METHODS AND RESULTS: In a cross-sectional study, a sample of individuals with CD and a group of healthy subjects were included. The dietary habits of all participants were recorded using a validated food frequency questionnaire, and the adherence to an MD was determined using the Italian Mediterranean Index. Typical Mediterranean food consumption was not significantly different between individuals with CD and the healthy participants, except for fruits (P = 0.017). However, individuals with CD consumed significantly higher amounts of potatoes (P = 0.003) and red and processed meat (P = 0.005) than healthy participants. The resulting mean Italian Mediterranean Index was significantly higher in healthy participants than in individuals with CD (P < 0.001). CONCLUSION: The results raise questions concerning the food choices of individuals with CD, suggesting the need of encouraging them to make better food choices more in line with an MD, which would improve their nutritional status and better protect them from NCDs at long term. PROTOCOL REGISTRATION: ClinicalTrials.gov (ID NCT01975155) on November 4 2013.

Intestinal permeability and Ménière's disease.

PURPOSE: Ménière disease (MD) is a multifactorial chronic disabling condition characterized by episodic vertigo, ear fullness, and hearing loss. MD patients often complain of aspecific gastrointestinal symptoms associated with autonomic dysregulation, frequently outweighed by the otological manifestations. Dietary modifications have been reported to improve the typical MD symptoms in some cases. Our purpose was to test the urinary levels of lactulose and mannitol (double sugar test) and the fecal calprotectin, both markers of altered intestinal permeability, in subjects with definite MD in an active and inactive stage. MATERIALS AND METHODS: Twenty-six with definite unilateral MD were studied: 14 patients were symptomatic for at least 3months with moderate to severe vertigo spells and a functional level ≥4; 12 patients had been asymptomatic (no vertigo spells) for at least 3months and had a functional level=1 at the time of testing. Twenty healthy volunteers were recruited as "control group". RESULTS: Lactulose and mannitol absorption was significantly increased in the symptomatic M patients compared to the asymptomatic group (p<0.02 and p<0.004, respectively) and to the controls. FC were also higher than normal only in the symptomatic group. (p<0.01). CONCLUSIONS: An altered intestinal permeability, according to the two assays, was found only in symptomatic MD patients. The rationale for a possible relationship between MD and intestinal permeability is forwarded. The double-sugar test and FC quantification might be implemented in the MD diagnostic workup.

Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megakaryopoiesis and myelofibrosis. We recently described the upregulation of MAF (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog) in PMF CD34+ hematopoietic progenitor cells (HPCs) compared to healthy donor. Here we demonstrated that MAF is also upregulated in PMF compared with the essential thrombocytemia (ET) and polycytemia vera (PV) HPCs. MAF overexpression and knockdown experiments shed some light into the role of MAF in PMF pathogenesis, by demonstrating that MAF favors the megakaryocyte and monocyte/macrophage commitment of HPCs and leads to the increased expression of proinflammatory and profibrotic mediators. Among them, we focused our further studies on SPP1 and LGALS3. We assessed SPP1 and LGALS3 protein levels in 115 PMF, 47 ET and 24 PV patients plasma samples and we found that SPP1 plasma levels are significantly higher in PMF compared with ET and PV patients. Furthermore, in vitro assays demonstrated that SPP1 promotes fibroblasts and mesenchymal stromal cells proliferation and collagen production. Strikingly, clinical correlation analyses uncovered that higher SPP1 plasma levels in PMF patients correlate with a more severe fibrosis degree and a shorter overall survival. Collectively our data unveil that MAF overexpression contributes to PMF pathogenesis by driving the deranged production of the profibrotic mediator SPP1.

Megaduodenum: an unusual presentation of amyloidosis?

Amyloidosis, a potentially fatal disease, is characterized by an abnormal deposition of autologous proteins. Heart, liver, kidneys, lung, thyroid, skin and the gastrointestinal tract can be involved; in this last case mucosal alterations or disturbances of the motility leading to pseudo-obstruction, bleeding, diarrhea and malabsorption can be present. However, the data concerning the possible gastrointestinal presentations of amyloidosis are scanty and heterogeneous. We report the case of a patient presenting severe gastrointestinal symptoms caused by a megaduodenum. The patient was thoroughly investigated and lesions appeared limited to the upper gastrointestinal tract in the absence of a systemic disorder. However, at follow up the patient developed cardiac dilatation and bioptic samples revealed the presence of amyloidosis.

Evaluation of GH-IGF-I axis in adult patients with coeliac disease.

The aim of this study was to evaluate GH/IGF-I axis and other pituitary functions in adult patients with coeliac disease. For this purpose, twenty-eight adult coeliac patients [20M, 8F:19-74 years; body mass index (BMI): 18.5-28 kg/m (2)] were recruited. Basal thyroid, adrenal and gonadal function, serum IGF-I and PRL, and routine parameters were evaluated. Dynamic GH secretion was carried out by GHRH plus arginine test. In 20 patients, antipituitary antibodies (APA) were also evaluated. Seven out of 28 patients, independently from disease onset and the gluten-free diet (GFD), showed an impaired GH secretion (25%). All were males, 2 with severe growth hormone deficiency (GHD) and 5 with partial GHD. In patients with GHD, as compared to coeliac patients with normal GH secretion, HOMA (2.1+/-1.2 vs. 0.9+/-0.4) and QUICKI (0.35+/-0.03 vs. 0.39+/-0.02) levels were significantly higher and lower, respectively, while IGF-I levels were slightly lower (17.7+/-3.7 vs. 24.7+/-6.3, p=NS). APA were negative in all 20 patients studied. In conclusion, a significant number of adult coeliac patients show an impaired GH secretion, this alteration being predominant in males and independent from disease onset and diet regimen. Given the absence of APAs, the cause of this pituitary dysfunction remains unclear even if a previous autoimmune involvement in some cases cannot be excluded.

Transglutaminases in inflammation and fibrosis of the gastrointestinal tract and the liver.

Transglutaminases are a family of eight currently known calcium-dependent enzymes that catalyze the cross-linking or deamidation of proteins. They are involved in important biological processes such as wound healing, tissue repair, fibrogenesis, apoptosis, inflammation and cell-cycle control. Therefore, they play important roles in the pathomechanisms of autoimmune, inflammatory and degenerative diseases, many of which affect the gastrointestinal system. Transglutaminase 2 is prominent, since it is central to the pathogenesis of celiac disease, and modulates inflammation and fibrosis in inflammatory bowel and chronic liver diseases. This review highlights our present understanding of transglutaminase function in gastrointestinal and liver diseases and therapeutic strategies that target transglutaminase activities.

A new simplified one port laparoscopic technique of peritoneal dialysis catheter placement with intra-abdominal fixation.

BACKGROUND: Various laparoscopic techniques have been described for the insertion of peritoneal dialysis catheters. However, most use 3 to 4 ports, thus multiplying the potential risk for abdominal wall complications (hemorrhage, hernia, leaking). METHODS: A Tenckhoff catheter was placed laparoscopically, using just 1 port, in 13 consecutive patients with end-stage renal failure. All catheters were fixed in the abdominal cavity with no additional ports for this purpose. RESULTS: After a follow-up of 76 patient-months, all catheters are working properly. There were no postoperative wall hemorrhages, early leaking, or hernias. There was 1 case of catheter migration and 2 cases of late leaking in 2 patients in total, due to severe constipation. There were no exit site or tunnel infections. One episode of peritonitis was successfully treated with antibiotics. CONCLUSION: The simplicity and the rapidity of the method justifies serious consideration for its use as the standard Tenckhoff catheter placement.

Magnesium homeostasis in patients undergoing continuous ambulatory peritoneal dialysis: role of the dialysate magnesium concentration.

We carried out this retrospective study to examine the magnesium status of our chronic ambulatory peritoneal dialysis (CAPD) patients dialyzed with 0.75 mmol/L (group I) or 0.50 mmol/L (group II) magnesium peritoneal dialysis solution. A total of 34 anuric patients on CAPD (age:31-72 years; duration of CAPD:7-74 months) were studied. None of them received magnesium-containing phosphate binders or vitamin D. Biochemical parameters including magnesium, calcium, phosphate, parathormone, and albumin were measured in all patients. The corrected for hypoalbuminemia serum magnesium concentration in group I was significantly higher compared to that found in group II. However, there were no significant differences in the other measured parameters between the two groups of CAPD patients, though iPTH levels were somewhat increased in group II patients. Serum magnesium levels were weakly correlated with serum prealbumin levels in both groups of CAPD patients (r=0.16, P=0.08 and r=0.17, P=0.07). The incidence of hypermagnesemia was significantly higher in group I patients versus those in group II (13/19 68.4%] vs. 2/15 13.3%], P<0.01). On the other hand, no patient developed hypomagnesemia (corrected total magnesium <0.65 mmol/L), despite the trend toward decreased magnesium levels in group II patients. Our results point out that serum iPTH levels and nutritional parameters, such as prealbumin levels, should be taken into account in the choice of the magnesium concentration of the peritoneal dialysis fluid.

Bread wheat gliadin cytotoxicity: a new three-dimensional cell model.

BACKGROUND: In an attempt to clarify the role of gliadin toxicity in the pathogenesis of gluten intolerance (celiac disease), previous in vitro studies have been based on two-dimensional human cell cultures. However, the specific morphological and biochemical properties of in vivo tissue are better maintained in three-dimensional cell cultures (multicellular spheroids, MCS). The aim of this study was to develop a three-dimensional in vitro model to investigate the effects of gliadin on epithelial cells and broaden our understanding of the early tissue damage occurring in celiac disease. METHODS: The three-dimensionally growing Lovo cell line was exposed to increasing concentrations of peptic-tryptic-digested bread wheat gliadin (from 125 to 1000 microg/mL) for 7 days in order to evaluate cell viability (colony-forming assay), and at the standard concentration of 500 microg/mL for 7 days in order to evaluate MCS diameters, volumes and cell morphology using light and electron microscopy. RESULTS: In comparison with the controls, the cell viability of the gliadin-treated MCS was significantly reduced (20-80%), but there was no difference in size. Various degrees of cell damage (autophagic vacuoles and intra-cytoplasmic lipid-like droplets) were detected by both light and electron microscopy. CONCLUSION: This is the first study investigating the effects of gliadin on MCS. Lovo MCS seem to be responsive to gliadin exposure, thus confirming previous results obtained using two-dimensional cell cultures. The data suggest that three-dimensional cell cultures may be useful in broadening our understanding of some of the early effects of gliadin peptides on epithelial cells.

In vitro cytotoxic effect of bread wheat gliadin on the LoVo human adenocarcinoma cell line.

The pathogenesis of celiac disease is not completely understood but, although the initial step of the process is still unclear, an altered immune response seems to play a major role. Previous studies of the biological properties of gliadin have highlighted its cytotoxic effects, and the aim of this study was to develop an in vitro technique to study them. The LoVo (human colon adenocarcinoma) cell line grown in two-dimensional cultures was exposed to different concentrations of digested bread wheat gliadin (62, 125, 250, 500 and 750 microg/ml) for 48 h, after which cell growth and oxidative balance (the content of reduced glutathione (GSH), and peroxidase, transferase and reductase activity) was evaluated. Other food proteins were used as controls. Our data revealed a statistically significant inhibition of cell growth in proportion to the gliadin concentration (from 26 to 100%), combined with a decrease in GSH content (-38% at 500 microg/ml) and reduced enzymatic activity (-30% at 500 microg/ml). The controls did not show any noxious effect. Our results confirm the usefulness of LoVo cells in evaluating gliadin cytotoxicity and that they can be used to investigate the biological properties of gliadin.