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.
In vitro model for IgE mediated food allergy Pizzuti, Daniela; Senzolo, Marco; Buda, Andrea ...
Scandinavian journal of gastroenterology,
02/2011, Letnik:
46, Številka:
2
Journal Article
Recenzirano
Abstract
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 1mg/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.
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.
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. Keywords: allergy, bread, baking, digestion, food processing, wheat proteins
BACKGROUNDActivated 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.
AIMTo 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.
METHODSSixty-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.
RESULTSSkin 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).
CONCLUSIONSerological 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.
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.
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.
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%).
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.
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.
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).
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.
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.
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