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Mitochondrial calcium (Ca 2+ ) uptake augments metabolic processes and buffers cytosolic Ca 2+ levels; however, excessive mitochondrial Ca 2+ can cause cell death. Disrupted mitochondrial function and Ca 2+ homeostasis are linked to numerous neurodegenerative diseases (NDs), but the impact of mitochondrial Ca 2+ disruption is not well understood. Here, we show that Drosophila models of multiple NDs (Parkinson's, Huntington's, Alzheimer's, and frontotemporal dementia) reveal a consistent increase in neuronal mitochondrial Ca 2+ levels, as well as reduced mitochondrial Ca 2+ buffering capacity, associated with increased mitochondria-endoplasmic reticulum contact sites (MERCs). Importantly, loss of the mitochondrial Ca 2+ uptake channel MCU or overexpression of the efflux channel NCLX robustly suppresses key pathological phenotypes across these ND models. Thus, mitochondrial Ca 2+ imbalance is a common feature of diverse NDs in vivo and is an important contributor to the disease pathogenesis. The broad beneficial effects from partial loss of MCU across these models presents a common, druggable target for therapeutic intervention., Competing Interests: Declaration of interests T.P.G. is now an employee of Costello Medical Consulting, Ltd., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Dopamine dyshomeostasis has been acknowledged among the determinants of nigrostriatal neuron degeneration in Parkinson's disease (PD). Several studies in experimental models and postmortem PD patients underlined increasing levels of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is highly reactive towards proteins. DOPAL has been shown to covalently modify the presynaptic protein αSynuclein (αSyn), whose misfolding and aggregation represent a major trait of PD pathology, triggering αSyn oligomerization in dopaminergic neurons. Here, we demonstrated that DOPAL elicits αSyn accumulation and hampers αSyn clearance in primary neurons. DOPAL-induced αSyn buildup lessens neuronal resilience, compromises synaptic integrity, and overwhelms protein quality control pathways in neurites. The progressive decline of neuronal homeostasis further leads to dopaminergic neuron loss and motor impairment, as showed in in vivo models. Finally, we developed a specific antibody which detected increased DOPAL-modified αSyn in human striatal tissues from idiopathic PD patients, corroborating the translational relevance of αSyn-DOPAL interplay in PD neurodegeneration., (© 2023. The Author(s).)

The protein DJ-1 is mutated in rare familial forms of recessive Parkinson's disease and in parkinsonism accompanied by amyotrophic lateral sclerosis symptoms and dementia. DJ-1 is considered a multitasking protein able to confer protection under various conditions of stress. However, the precise cellular function still remains elusive. In the present work, we evaluated fruit flies lacking the expression of the DJ-1 homolog dj-1β as compared to control aged-matched individuals. Behavioral evaluations included lifespan, locomotion in an open field arena, sensitivity to oxidative insults, and resistance to starvation. Molecular analyses were carried out by analyzing the mitochondrial morphology and functionality, and the autophagic response. We demonstrated that dj-1β null mutant flies are hypoactive and display higher sensitivity to oxidative insults and food deprivation. Analysis of mitochondrial homeostasis revealed that loss of dj-1β leads to larger and more circular mitochondria, characterized by impaired complex-I-linked respiration while preserving ATP production capacity. Additionally, dj-1β null mutant flies present an impaired autophagic response, which is suppressed by treatment with the antioxidant molecule N-Acetyl-L-Cysteine. Overall, our data point to a mechanism whereby DJ-1 plays a critical role in the maintenance of energy homeostasis, by sustaining mitochondrial homeostasis and affecting the autophagic flux through the maintenance of the cellular redox state. In light of the involvement of DJ-1 in neurodegenerative diseases and considering that neurons are highly energy-demanding cells, particularly sensitive to redox stress, our study sheds light on a key role of DJ-1 in the maintenance of cellular homeostasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Redox homeostasis is a vital process the maintenance of which is assured by the presence of numerous antioxidant small molecules and enzymes and the alteration of which is involved in many pathologies, including several neurodegenerative disorders. Among the different enzymes involved in the antioxidant response, SOD1 and DJ-1 have both been associated with the pathogenesis of amyotrophic lateral sclerosis and Parkinson's disease, suggesting a possible interplay in their mechanism of action. Copper deficiency in the SOD1-active site has been proposed as a central determinant in SOD1-related neurodegeneration. SOD1 maturation mainly relies on the presence of the protein copper chaperone for SOD1 (CCS), but a CCS-independent alternative pathway also exists and functions under anaerobic conditions. To explore the possible involvement of DJ-1 in such a pathway in vivo, we exposed Drosophila melanogaster to anoxia and evaluated the effect of DJ-1 on fly survival and SOD1 levels, in the presence or absence of CCS. Loss of DJ-1 negatively affects the fly response to the anoxic treatment, but our data indicate that the protective activity of DJ-1 is independent of SOD1 in Drosophila , indicating that the two proteins may act in different pathways.

During recent decades, model organisms such as Drosophila melanogaster have made it possible to study the effects of different environmental oxygen conditions on lifespan and oxidative stress. However, many studies have often yielded controversial results usually assigned to variations in Drosophila genetic background and differences in study design. In this study, we compared longevity and ROS levels in young, unmated males of three laboratory wild-type lines (Canton-S, Oregon-R and Berlin-K) and one mutant line (Sod1n1) as a positive control of redox imbalance, under both normoxic and hypoxic (2% oxygen for 24 h) conditions. Lifespan was used to detect the effects of hypoxic treatment and differences were analysed by means of Kaplan-Meier survival curves and log-rank tests. Electron paramagnetic resonance spectroscopy was used to measure ROS levels and analysis of variance was used to estimate the effects of hypoxic treatment and to assess ROS differences between strains. We observed that the genetic background is a relevant factor involved in D. melanogaster longevity and ROS levels. Indeed, as expected, in normoxia Sod1n1 are the shortest-lived, while the wild-type strains, despite a longer lifespan, show some differences, with the Canton-S line displaying the lowest mortality rate. After hypoxic stress these variances are amplified, with Berlin-K flies showing the highest mortality rate and most evident reduction of lifespan. Moreover, our analysis highlighted differential effects of hypoxia on redox balance/unbalance. Canton-S flies had the lowest increase of ROS level compared to all the other strains, confirming it to be the less sensitive to hypoxic stress. Sod1n1 flies displayed the highest ROS levels in normoxia and after hypoxia. These results should be used to further standardize future Drosophila research models designed to investigate genes and pathways that may be involved in lifespan and/or ROS, as well as comparative studies on specific mutant strains., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

DJ-1 is a multifaceted protein with pleiotropic functions that has been implicated in multiple diseases, ranging from neurodegeneration to cancer and ischemia-reperfusion injury. Ischemia is a complex pathological state arising when tissues and organs do not receive adequate levels of oxygen and nutrients. When the blood flow is restored, significant damage occurs over and above that of ischemia alone and is termed ischemia-reperfusion injury. Despite great efforts in the scientific community to ameliorate this pathology, its complex nature has rendered it challenging to obtain satisfactory treatments that translate to the clinic. In this review, we will describe the recent findings on the participation of the protein DJ-1 in the pathophysiology of ischemia-reperfusion injury, firstly introducing the features and functions of DJ-1 and, successively highlighting the therapeutic potential of the protein., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The population screening campaigns have resulted in increasing the prevalence of endoscopically resected colorectal cancers (CRCs) invading the submucosa (pT1). Synchronous nodal involvement occurs in less than 15 % of these tumors. Histologic criteria currently used for selecting patients needing resection are imprecise and most patients could have been simply followed-up. Tumor infiltrating lymphocytes (TILs) and mismatch repair (MMR) status impact on CRC prognosis. To identify patients requiring completion surgery, the value of histologic variables, TILs and MMR status as risk factors of nodal metastasis was investigated in screening detected and endoscopically removed pT1 CRCs., Methods: In 102 endoscopically resected pT1 CRCs, the cancer phenotype, CD3+ and CD8+ TILs, and MMR status were assessed. Univariate and multivariate analyses were used to evaluate the correlation with nodal metastasis., Results: Positive resection margin, evidence of vascular invasion and tumor budding, wide area of submucosal invasion, and high number of CD3+ TILs were associated with nodal metastasis in univariate analyses. Vascular invasion was statistically independent in multivariate analysis. Evidence of neoplastic cells in the vessels and/or at the excision border featured 5 out of 5 metastatic tumors and 13 out of 97 non-metastatic ones., Conclusions: Completion surgery should be recommended only in pT1 CRC with vascular invasion or with tumor cells reaching the margin. In all other cases, the treatment choice should result from a multidisciplinary discussion on the patient-centered evaluation of the risk-benefit ratio., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Reactive oxygen species (ROS) play an important role as endogenous mediators in several cellular signalling pathways. However, at high concentrations they can also exert deleterious effects by reacting with many macromolecules including DNA, proteins and lipids. The precise balance between ROS production and their removal via numerous enzymatic and nonenzymatic molecules is of fundamental importance for cell survival. Accordingly, many neurodegenerative disorders, including Parkinson's disease (PD), are associated with excessive levels of ROS, which induce oxidative damage. With the aim of coping with the progression of PD, antioxidant compounds are currently receiving increasing attention as potential co-adjuvant molecules in the treatment of these diseases, and many studies have been performed to evaluate the purported protective effects of several antioxidant molecules. In the present review, we present and discuss the relevance of the use of Drosophila melanogaster as an animal model with which to evaluate the therapeutic potential of natural and synthetic antioxidants. The conservation of most of the PD-related genes between humans and D. melanogaster , along with the animal's rapid life cycle and the versatility of genetic tools, makes fruit flies an ideal experimental system for rapid screening of antioxidant-based treatments., Competing Interests: The authors declare no conflict of interest.

Aim: To describe recent trends in hospital admission rates for alcoholic liver disease (ALD) in the Veneto region of Italy., Methods: This retrospective cohort study is based on anonymous hospital discharge records (HDRs) for 2000-2017 from all public and accredited private hospitals operating within the context of the Regional (Veneto) Health Services that are conserved in National/Regional database. It examined the HDR's of all the hospitalizations of the residents of the Veneto region that were registered under an ALD diagnosis. These were classified under three subheadings: acute alcoholic hepatitis Alcoholic liver cirrhosis and 'other ALD'., Results: During 2000-2017, 30,089 hospital admissions (out of a total regional population of 4,900,000) were registered for ALD. Hospitalization stratified by age showed that the percentage attributable to acute alcoholic hepatitis is higher in younger age groups: 42% in 15-24-year-old (odds ratios (ORs): 14.74; CI95%: 7-30.86; P < 0.000) and 15% in the 25-44-year-old (OR: 3.51; CI95%: 3.12-3.94; P < 0.000). A longitudinal analysis of hospitalization patterns showed a 7% increase in average age in both sexes (from 58.8 ± 9.2 to 62.4 ± 9.7) and a substantial decrease (63.5%) in standardized hospitalization rates (HRs, χ2 trend: 4099.827; P < 0.000) and a smaller decrease (47%) in standardized mortality rates (χ2 trend: 89.563; P < 0.000)., Conclusions: The fall in the overall ALD-related HR in the Veneto region can be explained by a decrease in population alcohol consumption. Increase in the HRs for acute alcoholic hepatitis in the age group 15-44 suggests an ongoing need for strategies to prevent alcohol abuse by young people., (© The Author(s) 2019. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

The preferential loss of dopaminergic neurons in the substantia nigra pars compacta is one of the pathological hallmarks characterizing Parkinson's disease. Although the pathogenesis of this disorder is not fully understood, oxidative stress plays a central role in the onset and/or progression of Parkinson's disease and dopamine itself has been suggested to participate in the preferential neuronal degeneration through the induction of oxidative conditions. In fact, the accumulation of dopamine into the cytosol can lead to the formation of reactive oxygen species as well as highly reactive dopamine-quinones. In the present work, we first analyzed the cellular damage induced by the addition of dopamine (DA) in the culture medium of SH-SY5Y cells, discriminating whether the harmful effects were related to the generation of reactive oxygen species or to the toxicity associated to dopamine-derived quinones. Then, we tested and demonstrated the capability of the antioxidant enzymes SOD1 and SOD2 to protect cells from the noxious effects induced by DA treatment. Our results support further exploration of superoxide dismutating molecules as a therapeutic strategy against Parkinson's disease.

Colorectal cancer (CRC) is a heterogeneous group of diseases both from the morphological and molecular point of view. The sessile serrated adenoma/polyp (SSA/P) has been proposed as the precursor lesion of CRCs characterized by CpG island methylator phenotype (CIMP), DNA mismatch repair (MMR) system deficiency, and BRAF gene mutations. However, no study so far investigated the molecular landscape of "sessile serrated" adenoma to carcinoma transition in early CRCs. Six formalin-fixed paraffin-embedded CRCs developed within SSA/P were profiled for the immunohistochemical expression of MMR proteins (MLH1, MSH2, MSH6, PMS2, and Ep-CAM), p16, and β-catenin. DNA was extracted from the two components of each sample, after microdissection, and characterized for CIMP status and by applying a custom hotspot multigene mutational profiling of 164 hotspot regions of eleven CRC-associated genes (AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN, and TP53). Five out of the six CRCs shared the same molecular profile (i.e. CIMP positive, MSI status, and BRAF mutation) with their SSA/P components. One out of five CRCs was also APC mutated, whereas another one showed an additional TP53 mutation. The remaining case was CIMP negative and MMR proficient in both the components, harbored a BRAF mutation in the SSA/P counterpart, whereas the CRC one was APC and TP53 mutated and showed p16 and β-catenin dysregulation. This study provides the molecular evidence that SSA/P, even without cytological dysplasia, is a precursor lesion of CRC and that conventional CRC might arise from mixed polyp., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Clinical and research studies have suggested a link between Parkinson's disease (PD) and alterations in the circadian clock. Drosophila melanogaster may represent a useful model to study the relationship between the circadian clock and PD. Apart from the conservation of many genes, cellular mechanisms, signaling pathways, and neuronal processes, Drosophila shows an organized central nervous system and well-characterized complex behavioral phenotypes. In fact, Drosophila has been successfully used in the dissection of the circadian system and as a model for neurodegenerative disorders, including PD. Here, we describe the fly circadian and dopaminergic systems and report recent studies which indicate the presence of circadian abnormalities in some fly PD genetic models. We discuss the use of Drosophila to investigate whether, in adults, the disruption of the circadian system might be causative of brain neurodegeneration. We also consider approaches using Drosophila , which might provide new information on the link between PD and the circadian clock. As a corollary, since PD develops its symptomatology over a large part of the organism's lifespan and given the relatively short lifespan of fruit flies, we suggest that genetic models of PD could be used to perform lifelong screens for drug-modulators of general and/or circadian-related PD traits.

Aging is the biggest risk factor for developing many neurodegenerative disorders, including idiopathic Parkinson's disease (PD). PD is still an incurable disorder and the available medications are mainly directed to the treatment of symptoms in order to improve the quality of life. Oxidative injury has been identified as one of the principal factors involved in the progression of PD and several indications are now reported in the literature highlighting the prominent role of the superoxide radical in inducing neuronal toxicity. It follows that superoxide anions represent potential cellular targets for new drugs offering a novel therapeutic approach to cope with the progression of the disease. In this review we first present a comprehensive overview of the most common cellular reactive oxygen and nitrogen species, describing their cellular sources, their potential physiological roles in cell signalling pathways and the mechanisms through which they could contribute to the oxidative damage. We then analyse the potential therapeutic use of SOD-mimetic molecules, which can selectively remove superoxide radicals in a catalytic way, focusing on the classes of molecules that have therapeutically exploitable properties.

Introduction: Driving under the influence of alcohol and/or psychoactive substances increases the risk of road accidents, but it is controversial whether this affects site and severity of injuries., Material and Methods: We search for alcohol, cannabinoids, cocaine, benzodiazepines, opioids, methadone, amphetamines and barbiturates in biological fluids of 1764 traumatized drivers admitted to the Emergency Department (ED) of Padua between 2010 and 2014., Results: We note correlation between alcohol and benzodiazepines and admission in ICU and between all the intoxications and the reserved prognosis. The sites of injuries were: head (37.13%), maxillofacial (8.33%), spinal column (44.67%), thoracic (15.31%), abdominal (5%), pelvic (2.55%) and limb traumas (23.58%). We observed a correlation between head trauma (p < 0.0001), maxillofacial trauma (p = 0.0418), thoracic trauma (p = 0.0215), pelvic trauma (p = 0.0008), spinal column trauma (p < 0.0001) and the totality of the intoxication and an association between benzodiazepines and thoracic and pelvic trauma., Conclusions: Alcohol and benzodiazepines intoxication increases the risk of reserved prognosis and admission in ICU; benzodiazepines intoxication correlates with thoracic and pelvic trauma.

In the context of colorectal cancer screening, we aimed to compare the effectiveness of different emotion-laden narratives, to investigate the specific emotions elicited at both subjective and physiological levels, and to test the effects of emotions explicitly expressed by the narrative character. Study 1 used a between-participants design comparing four conditions: relief-based narrative, regret-based narrative, control (test-uptake only) narrative, and standard invitation material (no-narrative condition). Study 2 used a mixed design, with the narrative content as a within-participants factor and whether emotions were expressed by the narrative character or not as between-participants factor. The main outcome measures were: intention to undergo testing (Studies 1 and 2), knowledge, risk perception, proportion of informed choices (Study 1), subjective emotional responses, changes in skin conductance, heart rate, and corrugator muscle activity (Study 2). In Study 1, relative to the non-narrative condition (51%), only the relief-based narrative significantly increased intention to undergo testing (86%). Relative to the standard invitation material, the narrative conditions did not decrease knowledge, alter risk perception, or decrease the proportion of informed choices. In Study 2, the relief-based narrative elicited the lowest self-reported negative affect, and received greater implicit attention, as suggested by the larger heart rate decrease. Making the emotions experienced by the narrative character explicit decreased negative affect, as indicated by the lower skin conductance and corrugator responses during reading. Our findings provide support for the use of a relief-based narrative with emotions expressed by the character in addition to the standard information material to promote colorectal cancer screening., Competing Interests: The authors have declared that no competing interests exist.

Worldwide, colorectal cancer (CRC) screening programs have significantly increased the detection of submucosal (pT1) adenocarcinoma. Completion surgery may be indicated after endoscopic excision of these potentially metastasizing early cancers. However, the postsurgical prevalence of nodal implants does not exceed 15%, leading to questions concerning the clinical appropriateness of any post-endoscopy surgery. Eastern scientific societies (Japanese Society for Cancer of the Colon-Rectum, in particular) include tumor budding (TB), defined as the presence of isolated single cancer cells or clusters of fewer than 5 cancer cells at the tumor invasive front, among the variables that must be included in histologic reports. In Western countries, however, no authoritative endorsements recommend the inclusion of TB in the histology report because of the heterogeneity of definitions and measurement methods as well as its apparent poor reproducibility. To assess the prognostic value of TB in pT1 CRCs, this meta-analysis evaluated 41 studies involving a total of 10137 patients. We observed a strong association between the presence of TB and risk of nodal metastasis in pT1 CRC. In comparing TB-positive (684/2401; 28.5%) versus TB-negative (557/7736; 7.2%) patients, the prevalence of nodal disease resulted in an odds ratio value of 6.44 (95% confidence interval, 5.26-7.87; P<.0001; I 2 = 30%). This increased risk of regional nodal metastasis was further confirmed after accounting for potential confounders. These results support the priority of histologically reporting TB in any endoscopically removed pT1 CRC to direct more appropriate patient management., (Copyright © 2017 Elsevier Inc. All rights reserved.)

For many years, novel strategies for cancer detection and treatment using nanoparticles (NPs) have been developed. Esophageal adenocarcinoma is the sixth leading cause of cancer-related deaths in Western countries, and despite recent advances in early detection and treatment, its prognosis is still very poor. This study investigated the use of fluorescent organic NPs as potential diagnostic tool in an experimental in vivo model of Barrett's esophageal adenocarcinoma. NPs were made of modified polysaccharides loaded with [4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran] (DCM), a well-known fluorescent dye. The NP periphery might or might not be decorated with ASYNYDA peptide that has an affinity for esophageal cancer cells. Non-operated and operated rats in which gastroesophageal reflux was surgically induced received both types of NPs (NP-DCM and NP-DCM-ASYNYDA) by intravenous route. Localization of mucosal NPs was assessed in vivo by confocal laser endomicroscopy, a technique which enables a "real time" and in situ visualization of the tissue at a cellular level. After injection of NP-DCM and NP-DCM-ASYNYDA, fluorescence was observed in rats affected by esophageal cancer, whereas no signal was observed in control non-operated rats, or in rats with simple esophagitis or Barrett's esophagus mucosa. Fluorescence was observable in vivo 30 minutes after the administration of NPs. Interestingly, NP-DCM-ASYNYDA induced strong fluorescence intensity 24 hours after administration. These observations suggested that NPs could reach the tumor cells, likely by enhanced permeability and retention effect, and the peptide ASYNYDA gave them high specificity for esophageal cancer cells. Thus, the combination of NP platform and confocal laser endomicroscopy could play an important role for highlighting esophageal cancer conditions. This result supports the potential of this strategy as a targeted carrier for photoactive and bioactive molecules in esophageal cancer diagnosis and treatment.

Background and Study Aims: Neoplastic lesions can be missed during colonoscopy, especially when cleansing is inadequate. Bowel preparation scales have significant limitations and no objective and standardized method currently exists to establish colon cleanliness during colonoscopy. The aims of our study are to create a software algorithm that is able to analyze bowel cleansing during colonoscopies and to compare it to a validate bowel preparation scale., Patients and Methods: A software application (the Clean Colon Software Program, CCSP) was developed. Fifty colonoscopies were carried out and video-recorded. Each video was divided into 3 segments: cecum-hepatic flexure (1st Segment), hepatic flexure-descending colon (2nd Segment) and rectosigmoid segment (3rd Segment). Each segment was recorded twice, both before and after careful cleansing of the intestinal wall. A score from 0 (dirty) to 3 (clean) was then assigned by CCSP. All the videos were also viewed by four endoscopists and colon cleansing was established using the Boston Bowel Preparation Scale. Interclass correlation coefficient was then calculated between the endoscopists and the software., Results: The cleansing score of the prelavage colonoscopies was 1.56 ± 0.52 and the postlavage one was 2,08 ± 0,59 (P < 0.001) showing an approximate 33.3 % improvement in cleansing after lavage. Right colon segment prelavage (0.99 ± 0.69) was dirtier than left colon segment prelavage (2.07 ± 0.71). The overall interobserver agreement between the average cleansing score for the 4 endoscopists and the software pre-cleansing was 0.87 (95 % CI, 0.84 - 0.90) and post-cleansing was 0.86 (95 % CI, 0.83 - 0.89)., Conclusions: The software is able to discriminate clean from non-clean colon tracts with high significance and is comparable to endoscopist evaluation.

Objective: Screening for HBV among groups at risk, such as migrant populations, has proved to be a cost-effective strategy. With a view to advising local policy-makers, the cost-consequences of HBV screening was assessed using a modeling approach., Methods: This cost-consequence analysis of an HBV screening strategy was conducted in a cohort of adult migrants in the province of Padua, northern Italy., Results: The population targeted for screening consisted of 65 405 migrants, among whom the weighted rate for the prevalence of HBV was 0.04972, with 3251 people infected. Over a period of 5 years, the screening strategy prevented 565 cases/year of chronic hepatitis, 141 of compensated cirrhosis, 9 of decompensated cirrhosis, 14 hepatocellular carcinomas and 12 deaths. The above data revealed that the incremental cost of the screening strategy compared to no screening strategy was € 7 974 959 over the five year period. The cost per life saved amounted to € 676 709., Conclusions: The present study provides useful information to policy-makers at local and regional levels.

Background: Activated eosinophils can infiltrate the intestinal mucosa in patients with inflammatory bowel disease (IBD), and eosinophils are also implicated in the histological damage seen in allergic diseases., Aim: To assess, in a group of patients with IBD in remission or with a mild disease activity, whether serological markers of eosinophil activation, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), are related to evidence of IgE hypersensitivity and to the eosinophilia in gut mucosa., Methods: Sixty-one patients with IBD (21 Crohn's disease and 40 ulcerative colitis) in remission or with a mild disease activity were screened for IgE hypersensitivity and serological levels of ECP and EPX. Colonic biopsies were taken to assess mucosal eosinophilic infiltration., Results: Skin prick test were positive in 31.1% of the patients with IBD, showing skin reactions to food allergens in 17.7%. Skin prick test findings were unrelated to ECP or EPX levels, or to clinical activity or eosinophil counts in the gut mucosa. A significant correlation was found between ECP and EPX levels (r=0.77; P<0.0001)., Conclusion: Serological ECP and EPX findings did not correlate with IgE hypersensitivity findings or eosinophilic colonic infiltration in patients with IBD in remission or with mild disease activity. The role of eosinophils in IBD needs to be better characterized in the colonic mucosa, instead of relying on serological tests.

Background: The role of C825T polymorphism of the candidate GNB3 gene in predicting cerebrovascular outcome has been poorly explored in longitudinal setting at a population level., Methods: In an epidemiological setting, 1,678 men and women from general population were genotyped for C825T polymorphism of GNB3 gene and follow-up for 10 years to detect nonfatal and fatal cerebrovascular events (CE). Established cerebrovascular risk factors were used to adjust the multivariate Cox analysis for confounders., Results: Seventy-three nonfatal and 30 fatal CE were recorded. Incidence of CE was higher in TT than in C-carriers (fatal: 2.6 vs. 1.7%, P < 0.03; nonfatal: 7.8 vs. 3.9%, P < 0.03; fatal recurrences: 1.6 vs. 0.6%, P < 0.03). In Cox analysis, the TT genotype predicted nonfatal (hazard ratio 1.99, 95% confidence interval 1.05-3.79, P = 0.03), fatal (2.91, 1.05-8.12, P = 0.04), and fatal recurrent CE (6.82, 1.50-31.1, P = 0.02) also after adjustment for age, gender, systolic and diastolic blood pressure, body adiposity, atherogenetic blood lipids, serum uric acid, diabetes, calories, caffeine and ethanol intake, and coronary events at baseline. Further adjustment for historical CE made the association between TT genotype and incident fatal CE nonsignificant (hazard ratio 2.72, 95% confidence interval 0.96-7.22, P = 0.06)., Conclusions: The TT genotype of GNB3 gene predicts incident CE independent of blood pressure and other established risk factors at a population level. Further studies are needed to clarify the nature and pathways of this association.

After rapid hypnotic induction, 12 healthy volunteers underwent hypnotic deepening with relaxation or with fractionation (without relaxation) in a random latin-square protocol. Electroencephalographic occipital alpha activity was measured, low-resolution brain electromagnetic tomography was performed, and hemodynamics (stroke volume, heart rate, cardiac output, mean arterial blood pressure, forearm arterial flow and resistance) were monitored in basal conditions and after deepening. After relaxation, both forearm flow (-18%) and blood pressure (-4%) decreased; forearm resistance remained unchanged. After fractionation, a forearm flow decrease comparable to that recorded after relaxation was observed, but blood pressure remained unchanged, leading to an increase of forearm resistance (+51%). Central hemodynamics did not change. Alpha activity increased in the precuneus after fractionation only. In conclusion, both relaxation and fractionation have vasoconstrictor effects, but fractionation is also associated with an increase in peripheral resistance.

In 288 men and women from general population in a cross-sectional survey, all neuropsychological tests were negatively associated with age; memory and executive function were also positively related with education. The hypertensives (HT) were less efficient than the normotensives (NT) in the test of memory with interference at 10 sec (MI-10) (-33%, P = 0.03), clock drawing test (CLOX) (-28%, P < 0.01), and mini-mental state examination (MMSE) (-6%, P = 0.02). Lower MMSE, MI-10, and CLOX were predicted by higher systolic (odds ratio, OR, 0.97, P = 0.02; OR 0.98, P < 0.005; OR 0.95, P < 0.001) and higher pulse blood pressure (BP) (OR 0.97, P = 0.02; OR 0.97, P < 0.01; and 0.95, P < 0.0001). The cognitive reserve index (CRI) was 6% lower in the HT (P = 0.03) and was predicted by higher pulse BP (OR 0.82, P < 0.001). The BP vectors of lower MMSE, MI-10, and CLOX were directed towards higher values of systolic and diastolic BP, that of low CRI towards higher systolic and lower diastolic. The label of hypertension and higher values of systolic or pulse BP are associated to worse memory and executive functions. Higher diastolic BP, although insufficient to impair cognition, strengthens this association. CRI is predicted by higher systolic BP associated to lower diastolic BP.

Background: In intestinal food allergy, the non-specificity of gastrointestinal symptoms and the limited access to the reacting organ are the reasons for the limited understanding of the pathophysiology of this disease and the difficulties in establishing an appropriate diagnosis in the individual patient., Objective: To develop an in vitro model reproducing pathophysiological mechanisms of IgE mediated food allergy., Methods: Distal duodenum biopsies of nine patients with food allergy and 10 control subjects were cultured for 3 h with medium alone and with 1 mg/ml of peptic-tryptic digest of wheat gliadin, wheat albumins, and apple proteins. Each biopsy was used for conventional histological examination and for immunohistochemical detection of IgE-positive cells. We have also analyzed the expression of tight junction proteins, occludin, claudin-1, and ZO-1 by immunoconfocal microscopy. Histamine and tryptase release were measured in the culture medium and collected at 0, 30 min, and 3 h of culture using an enzyme and radio immunoassay, respectively., Results: Exposure of small intestinal biopsy specimens of patients with food allergy to food allergens led to a significative increase of IgE-positive cells with a significative increase of histamine and tryptase release and an altered expression of tight junction proteins. No differences were found in intestinal biopsies of controls, cultured with or without food antigens., Conclusions: Small intestinal organ culture is a functional model of food allergy and could be considered as an in vitro oral food challenge, with evident reduction of costs and risks for the patients.

Background and Aims: A blood glucose (BG) fall after an oral glucose load has never been described previously at a population level. This study was aimed at looking for a plasma glucose trend after an oral glucose load for possible blood glucose fall if any, and for its impact on coronary mortality at a population level., Methods and Results: In subjects from an unselected general population, BG and insulin were detected before and 1 and 2h after a 75-g oral glucose load for insulin sensitivity and β-cell function determination. Blood pressure, blood examinations and left ventricular mass were measured, and mortality was monitored for 18.8±7.7 years. According to discriminant analysis, the population was stratified into cluster 0 (1-h BG < fasting BG; n=497) and cluster 1 (1-h BG ≥ fasting BG; n=1733). To avoid any interference of age and sex, statistical analysis was limited to two age-gender-matched cohorts of 490 subjects from each cluster (n=940). Subjects in cluster 0 showed significantly higher insulin sensitivity and β-cell function, lower visceral adiposity and lower blood pressure values. Adjusted coronary mortality was 8 times lower in cluster 0 than 1 (p<0.001). The relative risk of belonging to cluster 1 was 5.40 (95% CI 2.22-13.1)., Conclusion: It seems that two clusters exist in the general population with respect to their response to an oral glucose load, independent of age and gender. Subjects who respond with a BG decrease could represent a privileged sub-population, where insulin sensitivity and β-cell function are better, some risk factors are less prevalent, and coronary mortality is lower., (Copyright © 2009 Elsevier B.V. All rights reserved.)

Objectives: This study investigated the relationship between participants' expected levels of pain intensity before a colonoscopy, pain intensity experienced while they were undergoing this medical procedure (real-time pain), and their retrospective evaluation of this experience., Design: Correlational design. Regression analyses were performed and mediational models were tested., Methods: Ninety patients who were about to undergo a colonoscopy were asked to report the pain intensity on a scale ranging from 0 (no pain) to 10 (extreme pain). They reported the expected intensity of pain before the examination, their real-time intensity of pain every 60 s during the colonoscopy, and their global retrospective evaluation of the pain experienced when the procedure was over., Results: Results confirmed that, regardless of participants' gender, the variability of the real-time pain distribution was a significant predictor of the accuracy of recall (i.e. the discrepancy between recalled pain and mean real-time pain). Moreover, participants' pain expectations preceding the examination were a significant predictor of the accuracy of recall. It was further demonstrated that the effect of patients' expectations on the discrepancy was mediated by the real-time pain variability., Conclusions: The results of the present study provide useful indications about what the target of interventions aimed at reducing the bias in pain recall should be.

Humoral immune mechanisms may have a role in the neurological complications of celiac disease (CD). We assessed 71 CD patients for neurologic manifestations and presence of serum antibodies to neural antigens. Sixteen patients (22.5%) were found to have neurological deficits including headache, depression, entrapment syndromes, peripheral neuropathy, and epilepsy. Antibody reactivity to neural antigens was detected in 30/71 (42.2%) patients. There was no clear correlation between anti-neural reactivity and neurologic dysfunction. Follow-up of 62 patients did not reveal change in electrophysiology or antibodies, regardless of diet. However, in 2 patients with neuropathy, symptoms improved or worsened depending on the diet.

Background: About 2.5% of patients with idiopathic peripheral neuropathy or idiopathic dysautonomia have underlying celiac disease (CD). Antibodies to ganglioside have been reported in CD patients with neuropathy. No data are so far available on the presence in CD of acetylcholine receptor (AChR) antibodies. Muscle AChR antibodies are found in patients with myasthenia gravis, and ganglionic AChR antibodies in patients with autoimmune autonomic neuropathy., Objective: To determine the frequency of AChR antibodies in CD patients and assess possible correlations with neurological manifestations., Methods: Seventy CD patients (16 M, 54 F, mean age 36 years) underwent neurological and electrophysiological evaluation. AChR antibodies were detected with radioimmunoprecipitation assay. Sera from 15 age-matched patients with systemic lupus erythematosus (SLE) and 10 with Sjogren syndrome were studied as controls., Results: None of our CD patients complained of autonomic symptoms or fatigable weakness. Borderline titres (0.03-0.05 nmol/l) of ganglionic AChR antibodies were present in 4 patients, one affected with type I diabetes and one with subclinical neuropathy. Three of the 4 patients underwent cardiovascular autonomic function tests, which showed no abnormalities. Low levels of ganglionic AChR antibodies (0.05-0.10 nmol/l) were found in 2 SLE control patients, one of whom had a severe sicca complex. Muscle AChR antibodies (>1.0 nmol/l) were found in two CD patient and one control patient with SLE. Neither had symptoms or signs of myasthenia gravis., Discussion and Conclusions: CD is occasionally associated with neurologic disease, and with antibody reactivity to neuronal antigens. None of our CD patients had autonomic failure or significant levels of ganglionic AChR antibodies. Two CD patient and one control with SLE had muscle AChR antibodies without clinical evidence of myasthenia. The presence of antibodies in CD and in SLE patients may reflect a non-specific autoimmune response in these patients or may indicate subclinical autoimmune autonomic and neuromuscular involvement.

Acquired copper deficiency has recently been recognized as a cause of myeloneuropathy mimicking subacute combined degeneration due to vitamin B-12 deficiency. A remote history of gastric surgery is frequently associated with this syndrome. However, the very limited prevalence of severe copper deficiency in patients with a history of gastric surgery suggests that additional contributing factors are likely to be involved. We describe a patient with copper deficiency and a previous Billroth II partial gastrectomy for gastric carcinoma, presenting with severe myelo-optico-neuropathy, demyelinating lesions of the brain, and subjective hyposmia. An abnormal glucose breath test also revealed small bowel bacterial overgrowth syndrome. Copper replacement therapy associated with antibiotic therapy was effective in preventing further neurological damage and in obtaining mild improvement. We propose that copper status should be evaluated in all patients presenting with unexplained noninflammatory myeloneuropathy. Small bowel bacterial overgrowth syndrome should be investigated as a cause of generalized malabsorption and a possible contributing factor to copper deficiency after gastric surgery, as should occult zinc ingestion.

The aim of this study was to evaluate the impact of applying strict selection criteria to patients with symptoms of obstructed defecation, rectocele and rectal prolapse who were candidates for surgery. From June 2001 to September 2003, 20 patients underwent surgery in our clinic for symptomatic rectocele and anorectal prolapse. They were evaluated prospectively using a dedicated questionnaire (KESS), a proctological and gynaecological examination, colpo-cysto-defecography and anorectal manometry before surgery and 6 months postoperatively. Strict selection criteria were used for surgery. After 6 months the questionnaire showed an important improvement in symptoms. The symptoms of obstructed defecation and vaginal bulging improved significantly. The average KESS score dropped from 17.65 preoperatively to 5.8 six months after surgery. In the treatment of pelvic floor disease, it is important to evaluate both the uro-gynaecological and the proctological symptoms with the utmost care, obtaining an accurate clinical picture with the aid of dedicated questionnaires and a thorough clinical examination. Evaluation of the effectiveness of surgery for constipation necessarily includes assessing the strength of the indications for surgery, irrespective of the surgical technique adopted, but there is currently no standardised test method for recording and comparing the symptoms of constipation.

Colitis cystica profunda is a rare intestinal lesion. Because of its clinical expression (rectorrhagia, mucorrhea and abdominal pain) and the way it appears to current imaging techniques this disease presents features which can be associated with colon neoplasm. Its diagnosis has to be confirmed histologically, and its etiology remains unclear. The following is a case report of colitis cystica profunda recurring 20 years after a first episode in a white woman, who had had an anterior resection of the sigmoid colon and upper rectum to deal with a colitis cystica profunda-induced stenosis of the sigmoid colon and at 41 underwent the transanal removal of a polypoid lesion. A review of 20 cases in the literature showed that colitis cystica profunda has a predilection for the male and generally affects the medial and lower rectum and the sigmoid colon. The literature also confirmed the association with ulcerative rectocolitis, Crohn's disease and rectal prolapse. The type of treatment varies from surgical, medical, and endoscopic to no treatment at all.

Antibodies to gangliosides and Purkinje cells have been reported in patients with celiac disease (CD) with neuropathy and ataxia, respectively. Whether these antibodies are pathogenic is not clear. The response of neurological symptoms and antibody titers to a gluten-free diet is still controversial. The objective of our study was to assess whether neurological manifestations in CD patients correlate with antibody titers and a gluten-free diet.Thirty-five CD patients (9 males, 26 females, mean age 37.1 +/- 12.6 yrs) were followed prospectively. At initial evaluation, 23 were on a gluten-free diet, 12 were not. At recruitment and during follow-up, patients underwent neurological and electrophysiological evaluation. IgG, IgM, and IgA anti-ganglioside antibodies were assayed by ELISA; anti-neuronal antibodies were assessed by immunohistochemistry and Western blot. Four patients, all males, had electrophysiological evidence of neuropathy; three had been on a gluten-free diet for several months, and one was newly diagnosed. One had reduced tendon reflexes; another complained of distal paresthesias. With regard to anti-ganglioside antibodies, three patients had a moderate increase in antibodies without symptoms or signs of neuropathy. No patients had ataxia or cerebellar dysfunction, although in four patients reactivity to neuronal antigens was found. In 17 patients, an electrophysiological follow-up (mean duration of follow-up, 9 months) showed no changes. In conclusion, the preliminary results of this prospective study indicate that neuropathy, usually subclinical, may accompany CD. Antibody titers do not seem to correlate with neurological symptoms/signs or diet. Ongoing follow-up will help confirm these data and clarify the role, if any, of antibodies in neurological involvement in CD.

Colonic diverticular disease is a benign condition typical of the Western world, but it is not rare for even the 1st episode of diverticulitis to carry potentially fatal complications. The evolution of a peridiverticular process generally poses problems for medical treatment and exposes patients to repeated episodes of diverticulitis, making surgical treatment necessary in approximately 30% of symptomatic patients. One of the most worrying complications of diverticulosis is internal fistula. The most common types of fistula are colovesical and colovaginal, against which the uterus can act as an important protective factor. The symptoms and the clinical and instrumental management of patients with diverticular fistulas are much the same as for patients with episodes of acute diverticulitis. Staging of the disease (according to Hinchey) should be done promptly so that the necessary action can be taken prior to surgery, implementing total parenteral nutrition (TPN), nasogastric aspiration and broad-spectrum antibiotic treatment. The best surgical approach to adopt in patients with diverticulitis complicated by fistula is still not entirely clear, though the 3-step strategy is currently tending to be abandoned due to its high morbidity and mortality rates. There is a widespread conviction, however, that the 2-step strategy (Hartmann, or resection with protective stomy) and the 1-step alternative should be reserved, respectively, for patients in Hinchey stages 3, 4 and 1, 2 with a situation of attenuated local inflammation. The 1-step approach seems to be safe and effective. This report describes a case of colovaginal fistula in a patient with colonic diverticulosis who had recently undergone hysterectomy, but who, unlike such cases in the past, was treated in a single step using a laparoscopic technique.

Unlabelled: Coeliac disease is an autoimmune enteropathy characterized by an enhanced permeability of the intestinal epithelial barrier. In epithelial cells paracellular permeability is regulated by intercellular tight junction. The cytoplasmic protein ZO-1 interacts directly with F-actin and plays a pivotal role in the structural and functional organization of tight junction., Aim: The aim of this study was to investigate the expression and localization of ZO-1 in the intestinal mucosa of coeliac patients., Patients and Methods: Twenty patients with active coeliac disease, seven of whom underwent a repeat biopsy following a gluten-free diet and 27 control subjects, were studied. In all subjects, three biopsies were obtained from distal duodenum during upper gastrointestinal endoscopy. ZO-1 protein localization and levels were detected by immunofluorescence followed by confocal microscopy analysis and immunoblotting. ZO-1 mRNA expression was assessed by RT-PCR. F-actin distribution was also investigated., Results: In patients with active coeliac disease, both ZO-1 protein levels and mRNA were clearly reduced. Cytoskeletal organization was disrupted with F-actin staining concentrated at the subcortical and basal surface regions. Abnormalities in ZO-1 expression and actin organization were reversed after a gluten-free diet., Conclusions: In active coeliac disease, ZO-1 protein expression is downregulated at the transcriptional level in association with F-actin redistribution. These changes are completely reversed after a gluten-free diet and could contribute to the increased intestinal paracellular permeability observed in this disorder.

Background: Helicobacter pylori is thought to be involved in atrophic body gastritis. We explored the prevalence of H. pylori infection in asymptomatic subjects with gastric parietal cell antibodies, as well as in patients with pernicious anemia, to evaluate a possible role of H. pylori gastric infection in gastric autoimmunity., Patients and Methods: We studied 79 consecutive asymptomatic subjects with parietal cell antibodies, 24 patients with pernicious anemia, and 66 parietal cell antibody-negative controls. All patients underwent gastric biopsies for histology and detection of H. pylori. Red blood cell count and volume, serum levels of gastrin, pepsinogen I, iron, folic acid, vitamin B12, and circulating antibodies to H. pylori and to intrinsic factor were also determined., Results: We found an atrophic body gastritis in 14 of the 79 asymptomatic subjects with parietal cell antibodies (18%) and in 2 of the 66 controls (3%) (p =.01). Mean levels of gastrin were increased (p <.0001), while those of pepsinogen were reduced (p <.001) compared with controls. H. pylori was identified at the gastric level and/or circulating anti-H. pylori antibodies were detected in 46 parietal cell antibody-positive subjects (58%) compared with 26 controls (39%) (p =.03). In patients with pernicious anemia we found an atrophic body gastritis in 18 of 24 cases (75%) (p <.001 vs. controls). Mean levels of gastrin were markedly increased (p <.0001) and those of pepsinogen I decreased (p <.0001) relative to controls. Only five of these patients (21%) had evidence of H. pylori infection compared with 46 of the parietal cell antibody-positive subjects (58%) (p =.003) and 26 of the controls (39%). Considering all patients with gastric autoimmunity (i.e. with parietal cell antibodies and/or with pernicious anemia), H. pylori was found in 44 of 72 of those without atrophy (61%) but in 6 of 31 with gastric body atrophy (19%) (p <.001), indicating that H. pylori infection is greatly reduced when gastric acid secretion decreases., Conclusions: The frequent detection of H. pylori infection in subjects with early gastric autoimmunity, indicated by the presence of parietal cell antibodies, suggests that H. pylori could have a crucial role in the induction and/or the maintenance of autoimmunity at the gastric level.

Background/aims: Serum sCD30 (soluble CD30) is a marker of cells producing Th2-type (T-helper-2-type) cytokines. High levels of sCD30 have been found in the active phase of HBV infection. The Th2-type cytokine profile has been documented in alcoholic liver diseases, which have particularly high IgE and IgA serum levels. The aims were: 1) to evaluate sCD30 levels in patients with (a) alcoholic liver diseases and (b) HCV-related chronic hepatitis before and after interferon treatment; 2) to correlate sCD30 concentrations with IgE and IgA serum levels., Methodology: Serum samples from 34 HCV-related chronic hepatitis patients, before and after interferon treatment, and 17 alcoholic liver disease patients were tested for sCD30 using the ELISA method (Dako, CD30-Ki-1 Antigen, Denmark)., Results: Significantly higher levels of sCD30 were found in alcoholic liver disease than in HCV-related chronic hepatitis patients (73.3 +/- 120 vs. 27.5 +/- 44 U/mL, P < 0.05). Alcoholic liver disease patients also exhibited significantly higher levels of IgA than HCV-related chronic hepatitis patients (P < 0.0001). No correlation was found between sCD30 and serum IgA or IgE or response to interferon., Conclusions: Th2 cells are strongly expanded in alcoholic liver diseases, though the particular immunoglobulin profile observed in this condition has yet to be explained. Th2 function also plays a crucial part in chronic HCV infection, but seems unrelated to interferon response.

The effect of baking and digestion on the allergenicity of wheat flour proteins has been studied. Pooled sera of patients suffering from food allergy to wheat products were tested for IgE binding to the proteins of the wheat dough and of the bread crumb and crust, before and after being in vitro digested. During in vitro digestion, the IgE binding protein components of the unheated dough tended to disappear, whereas a permanence of IgE recognition was evident for both the bread crumb and crust. This indicates that the baking process increases the resistance of the potential allergens of the wheat flour to proteolytic digestion, allowing them to reach the gastrointestinal tract, where they can elicit the immunological response. Therefore, the effects of baking must be carefully considered in studying food allergies to wheat products.

Background: The involvement of IgE-mediated hypersensitivity reactions in the genesis of gastrointestinal symptoms after ingestion of foods containing wheat has been rarely reported., Objective: To detect IgE specifically binding to wheat proteins in the sera of atopic and non-atopic patients suffering from gastrointestinal symptoms after ingestion of wheat and to evaluate the reliability of skin prick test and CAP in the diagnosis of food allergy to wheat., Methods: The sera of patients (10 atopic and 10 non-atopic) previously diagnosed as suffering from irritable bowel syndrome and complaining of symptoms after wheat ingestion were analysed by immunoblotting for IgE binding to water/salt-soluble and insoluble wheat flour proteins., Results: All the atopic patients and only one of the non-atopic patients were positive to wheat CAP. For the patients tested, skin prick test was positive for all the atopic patients and for only one of the non-atopic patients. However, immunoblotting experiments showed the presence of specific IgE to wheat proteins in all the patients. Ten out of 11 of the wheat CAP-positive patients had IgE binding to a soluble 16-kDa band, but the same band was recognized, in a slighter way, by only two out of nine of the wheat CAP-negative patients. Moreover, although almost all of the patients were negative in CAP testing with gluten, 19 out of 20 recognized protein bands belonging to the prolamin fraction., Conclusions: For the atopic patients the positivity to skin prick test and CAP to wheat was in accordance with the immunoblotting results and a food allergy to wheat could be diagnosed. In these patients a major allergen was a 16-kDa band corresponding to members of the cereal alpha-amylase/trypsin inhibitors protein family, the major allergens involved in baker's asthma. In the non-atopic patients the positive immunoblotting results contrasted with the responses of the allergologic tests, indicating that the allergenic wheat protein preparations currently used are of limited value in detecting specific IgE to wheat and that the fraction of irritable bowel syndrome (IBS) patients with food allergy may be larger than believed.

Objective: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with clinical signs typical of "intestinal" food allergies or intolerance. The aim of this study was to characterize the clinical features of IBS patients suspected of suffering from adverse reactions to food., Methods: The study involved 128 consecutive IBS patients divided into four groups according to their main symptom on presentation at our outpatient clinic. A detailed medical history was recorded, paying particular attention to any allergies and reported intolerance to food. Each patient was screened for allergies; intestinal permeability tests was performed in randomly selected patients from different groups. Findings were analyzed using the chi2 test., Results: Adverse reactions to one or more foods were reported by 80 patients (62.5%); skin prick tests (SPT) were positive in 67 patients (52.3%) with no significant differences between patients complaining of different symptoms. Patients who reported a food intolerance had more positive SPTs than those who did not (47 of 80 [58.7%] vs 20 of 48 [41.7%]); this difference was not statistically significant, although it suggests a trend (p < 0.0610). There was little consistency between the specific foods reported to cause intolerance and those resulting from the tests (11 of 80 patients, 13.7%). The intestinal permeability test was normal in 29 of 33 patients (87.9%)., Conclusions: More than 50% of IBS patients were found sensitized to some food or inhalant without any typical clinical signs. Patients were unable to identify potentially offending foods. The lack of a correlation between SPT results and reported food allergies needs further investigation to clarify the pathophysiology and improve the diagnosis of intestinal food allergies.

The correlation between therapeutic response and liver fibrogenesis was studied in serum and liver specimens taken from 31 patients treated with alpha-interferon (IFN) (14 sustained responders and 17 non-responders) for chronic hepatitis C. Serum samples, collected before therapy, and at further 6-month intervals over 2 years, were tested for markers of liver neofibrogenesis. Serum N-terminal procollagen III peptide (PIIINP) displayed a significant and persistent decrease (P < 0.05) in sustained responders but not in non-responders; significantly lowered (P < 0.05) mean levels of C-terminal procollagen I peptide (PICP) were transiently observed in both patient groups, apparently as a result of IFN administration. Serum laminin (Lam) levels remained unchanged. One year after the cessation of treatment, liver biopsy re-testing showed an improvement in necro-inflammatory scores only in sustained responders, with the histological fibrosis scores remaining unaltered in both groups. IFN treatment seemed to exert an influence on serum levels of markers of hepatic connective tissue turnover even in patients that did not respond to therapy, while no effect was observed on preexistent liver fibrosis.

Recurrent aphthous stomatitis is a frequently occurring disorder which may be a clinical feature of systemic disease. For many other patients, it is a tedious problem often having no known cause. The aim of this study was to verify if immune responses to common foods and/or viruses are involved in the etiopathogenesis of recurrent aphthous stomatitis. Sixteen patients with this disorder were studied by measurement of immunoglobulin classes (IgG, IgA, IgM), blood lymphocyte subpopulations, blood circulating immune complexes, and complement fractions (C3 and C4). Intradermal skin tests for common food and inhalant allergens were performed in all cases. In 5 patients with positive skin tests, serum specific IgE were tested for the same allergens by radioallergosorbent test. Skin patch tests for dental material were performed in all cases. Oral mucosal biopsies and/or cytology samples were taken in 10 cases for histopathological evaluation and in situ hybridization for Papillomavirus, Cytomegalovirus, Herpes simplex virus I and II, Epstein Barr virus. In 13 patients, lymphocyte subpopulations were altered, with a reduced CD4/CD8 ratio. No other alterations of serum immunological parameters were observed. Skin patch tests for dental material were negative in all cases, while skin tests for food allergens were positive in 5 cases (not confirmed by radioallergosorbent test or food challenge tests). Virus antigen and DNA were not found in mucosal specimens, although one patient was positive for Epstein Barr virus DNA by in situ hybridization. An alteration of the CD4/CD8 ratio was demonstrated in most of the patients with recurrent aphthous stomatitis, although immune responses to food and/or dental material and/or common viruses did not seem to be involved in the etiopathogenesis of this disorder.

Background: Cord blood IgE levels have been studied as a possible marker of allergy in infants but few studies are available in our Region. The aim of this paper was to test IgE levels in cord blood of 60 consecutive newborns in a restricted area of Veneto, to correlate cord blood IgE levels with family history of allergy and to verify the risk of contamination from mother's blood., Methods: Cord blood was obtained from 60 consecutive newborns. Immunoglobulin levels (IgG, IgA, IgM, and IgE) were measured in cord blood of newborns and in serum of all mothers. Family history for allergy was previously investigated from the mothers., Results: IgE were detectable in cord blood of 5 newborns but only 2 of them had positive family history for allergy which was pointed out in 11/60. In one of these cases the contamination of sample from mother's blood was postulated. IgG levels in newborn cord blood were higher than in mothers' blood and it was not related with IgE levels or other investigated factors., Conclusions: Only 6.6% of newborns in a restricted area of Veneto region have detectable IgE in cord blood whereas 18.3% of them have positive family history for allergy. Measurable levels of IgE in cord blood are not related with positive family history of allergy and are rarely influenced by mothers' blood contamination.

Aims: Interferon alpha has been reported to enhance autoantibody production and to increase the risk of autoimmunity particularly against thyroid tissue. We designed a study with the following aims: 1) to assess the incidence of organ- and non-organ-specific autoantibodies during Interferon treatment; 2) to evaluate whether these autoantibodies have any clinical relevance; 3) to establish whether the development of autoimmune disorders can be related to a genetic predisposition., Methods: A panel of 5 non-organ-specific and 6 organ-specific autoantibodies was evaluated in serum samples collected before treatment and then at 3 and 12 months in 47 patients enrolled in a treatment protocol with a 2b-recombinant Interferon (3 MU, 3 times a week for 12 months). In the second part of the study we explored genetic predisposition for autoimmune disorders in 31 patients by DNA-HLA class II typing using Restriction Fragment Length Polymorphism (RFPL)., Results: Non-organ-specific autoantibodies were absent in all patients before and after Interferon. During follow-up 6 patients showed an increment in thyroid microsomal antibody titres; 3 of these also developed thyroglobulin autoantibodies; 3 of the 6 patients developed persistent hypothyroidism; a fourth had a transient subclinical hypothyroidism and a fifth had a transient subclinical hyperthyroidism. Two patients with initial positivity for ICA and PCA maintained their reactivity during treatment without impairment of the respective target organs. Eight out of 39 initially negative patients developed one or more organ-specific autoantibodies during follow-up. One of these developed a persistent hypothyroidism, and another developed insulin-dependent diabetes. HLA-typing did not reveal any particular allele frequency in patients with thyroid antibody positivity as compared with those without autoantibodies and controls. Moreover, four of the 6 patients positive for islet-cell antibodies were carrying the non-Asp 57 allele which is considered a marker of a genetic predisposition for insulin-dependent diabetes., Conclusions: These findings suggest that, besides the thyroid gland, pancreatic beta-cells could be a target of autoimmunity during Interferon-treatment for chronic HCV hepatitis. A genetic predisposition may be important, though insufficient alone, in the development of Interferon-induced autoimmune phenomena.

Gastric ectopias in the upper oesophagus and hypopharynx are relatively rare and often misinterpreted. They may become symptomatic due to the onset of a fistula involving adjacent structures in the neck. This case report describes a 20-year-old patient with swallowing difficulties and laterocervical pain, with a diagnosis of fistula of the pyriform sinus due to secernent gastric mucosal ectopia. The significance of this case lies in the fact that accurate aetiopathogenic study and careful differential diagnostic procedures enabled the proper identification of this rare upper oesophageal pathology, which is often misdiagnosed due to the technical difficulties involved in conventional endoscopy of the digestive tract.

Allergic mechanisms have been shown to induce gastric and intestinal damage in animal models. It has been demonstrated that people allergic to food may complain of gastrointestinal disorders. Furthermore food allergens can induce gastric mucosal damage in sensitized people. Little is known as regards allergic mechanisms underlying "peptic" ulcers although there are reports suggesting that some forms of gastric and duodenal ulcer may be caused by allergy. AIM. Of the study was to evidence if IgE specific to food and inhalants are localized in gastric and duodenal mucosa and if the in vitro incubation of gastric and duodenal biopsies with specific allergens, stimulate mast-cell mediators. MATERIALS AND METHODS. Twenty-one patients affected by gastric/duodenal ulcers (14 with high total IgE serum levels) and 16 controls were studied. All patients were submitted to upper digestive endoscopy and biopsies were taken from gastric fundus, body and antrum and duodenal bulb. Specific IgE to food and inhalant allergens were tested after homogenization of biopsies, using commercial kits. In 3 selected patients, 3 biopsies from gastric fundus and 3 from duodenal bulb were taken. After incubation of mucosal of mucosal biopsies with allergens (wheat, lactoalbumin, Parietaria J. pollen), the release of histamine and tryptase was measured. The release of Pepsinogen A was measured in the same conditions, as control. RESULTS. Specific IgE to food and inhalants allergens have been found in 164/586 tests (27.9%) of "peptic" ulcer patients and in 17/430 tests (4%) of controls. The duodenal bulb resulted the site in which most frequently IgE have been found. The release of histamine and tryptase has been stimulated only in 1/6 tests by incubation of biopsies with specific allergens in patients with specific IgE. PG-A release has been always stimulated by incubation of gastric biopsies, but not duodenal biopsies, with all tested allergens. DISCUSSION AND CONCLUSION. Specific IgE may be localized in gastric and duodenal mucosa of patients with "peptic" ulcer and/or food allergy. This event is linked to high total IgE serum levels and in a lesser extent, intestinal parasitosis, it is not strictly correlated with specific IgE in the serum and it regards both food and inhalant allergens. No relevant effects were observed after incubation of specific allergens with gastric or duodenal mucosa biopsies containing specific IgE. The possibility that higher allergens concentration stimulate mediator release from mast cells should be investigated. A defect of the gastric or duodenal epithelial barrier which permit a passage way for proteins with subsequent IgE production in the submucosa, appears to be the cause of localization of specific IgE in stomach and duodenum.

The prevalence of high total IgE serum levels was evaluated in 232 consecutive patients suffering from peptic ulcer. Twenty-one percent of the patients presented total IgE serum levels above 200 KU/L compared with the 5% found in a healthy control population (p < 0.004). Similar prevalence was found in gastric and/or duodenal ulcers. No significant differences in the duration of the disease, smoking habits, familiarity for peptic ulcer, symptomatology and frequency of complications were observed between patients with high and with normal total IgE serum levels. Gastric function studies (gastric acid secretion, serum pepsinogen and gastrin levels) did not show any significant differences between the two groups. The incidence of Helicobacter pylori infection was 65% in patients with normal IgE levels and 75% in those with high IgE levels (p: n.s.). The response to treatment with full dose of H2-receptor antagonists was comparable in both groups (91.25% and 90.7% of ulcer healing after 6-8 weeks of treatment). A relapse of the ulcer after 6 months of maintenance therapy (half dose of H2-receptor antagonists) was observed in 39.5% of the patients with ulcer and high total IgE serum as against the 11.9% observed in patients with normal IgE (p < 0.001). These data lend further support to the hypothesis of an underlying immuno-allergic reaction in some forms of gastric or duodenal ulcer.