Carmelo Sciume

60KDa chaperonin (HSP60) is over-expressed during colorectal carcinogenesis.

The aim of the present study was to evaluate the expression of the heat shock protein 60 (HSP60), a mitochondrial matrix-associated protein belonging to the chaperonin family, in colorectal adenomas and cancers, comparing them to normal colonic tissues and hyperplastic polyps. We performed both immunohistochemistry and Western blot analysis for HSP60. Immunohistochemistry resulted positive in all tubular adenomas and infiltrating adenocarcinomas. By contrast, normal tissues and hyperplastic polyps were negative. Quantitative analysis showed that tubular adenomas with different levels of dysplasia did not present statistical differences concerning HSP60 positivity. In addition, carcinomas always showed the highest expression. Western blot analysis confirmed these observations. These data suggest that HSP60 over-expression is an early event in carcinogenesis. We suspect that HSP60 plays a different role in colorectal carcinogenesis with respect to that in normal cells, which foresees its possible use as diagnostic and prognostic tools.

High Proportions of People With Nonceliac Wheat Sensitivity Have Autoimmune Disease or Antinuclear Antibodies

BACKGROUND & AIMS There is much interest in wheat sensitivity among people without celiac disease (CD), but little is known about any risks associated with the condition. We evaluated the prevalence of autoimmune diseases (ADs) among patients with nonceliac wheat sensitivity (NCWS), and investigated whether they carry antinuclear antibodies (ANA). METHODS We performed a retrospective study of 131 patients diagnosed with NCWS (121 female; mean age, 29.1 years) at 2 hospitals in Italy from January 2001 through June 2011. Data were also collected from 151 patients with CD or irritable bowel syndrome (IBS) (controls). Patient medical records were reviewed to identify those with ADs. We also performed a prospective study of 42 patients (38 female; mean age, 34 years) diagnosed with NCWS from July 2011 through March 2014 at 3 hospitals in Italy. One hundred age- and sex-matched subjects with CD or IBS served as controls. Serum samples were collected from all subjects and ANA levels were measured by immunofluorescence analysis. Participants completed a questionnaire and their medical records were reviewed to identify those with ADs. RESULTS In the retrospective analysis, similar portions of subjects with NCWS (29%) and CD (29%) developed ADs (mainly Hashimotos thyroiditis, 29 cases), compared with a smaller proportion of subjects with IBS (4%) (P < .001). In the prospective study, 24% of subjects with NCWS, 20% of subjects with CD, and 2% of subjects with IBS developed ADs (P < .001). In the retrospective study, serum samples tested positive for ANA in 46% of subjects with NCWS (median titer, 1:80), 24% of subjects with CD (P < .001), and 2% of subjects IBS (P < .001); in the prospective study, serum samples were positive for ANA in 28% of subjects with NCWS, 7.5% of subjects with CD (P = .02), and 6% of subjects with IBS (P = .005 vs patients with NCWS). ANA positivity was associated with the presence of the HLA DQ2/DQ8 haplotypes (P < .001). CONCLUSIONS Higher proportions of patients with NCWS or CD develop autoimmune disorders, are ANA positive, and showed DQ2/DQ8 haplotypes compared with patients with IBS.

Antiendomysium antibodies assay in the culture medium of intestinal mucosa: an accurate method for celiac disease diagnosis.

Background Celiac disease (CD) diagnosis is becoming more difficult as patients with no intestinal histology lesions may also be suffering from CD. Aim To evaluate the diagnostic accuracy of antiendomysium (EmA) assay in the culture medium of intestinal biopsies for CD diagnosis. Patients and methods The clinical charts of 418 patients with CD and 705 non-CD controls who had all undergone EmA assay in the culture medium were reviewed. Results EmA assay in the culture medium had a higher sensitivity (98 vs. 80%) and specificity (99 vs. 95%) than serum EmA/antibodies to tissue transglutaminase (anti-tTG) assay. All patients with CD who were tested as false-negatives for serum EmA and/or anti-tTG (32 adults and 39 children) carried the human leukocyte antigen alleles associated to CD. Furthermore, during the follow-up, four patients with negative-serum EmA/anti-tTG, normal villi architecture, and positive-EmAs in the culture medium, developed villous atrophy and underwent gluten-free diet with consequent resolution of the symptoms and complete intestinal histology recovery. Conclusion EmA assay in the culture medium should be included in the diagnostic criteria for CD diagnosis in ‘seronegative’ patients.

Heat Shock Protein 60 Levels in Tissue and Circulating Exosomes in Human Large Bowel Cancer Before and After Ablative Surgery

Heat shock protein 60 (Hsp60) is a chaperonin involved in tumorigenesis, but its participation in tumor development and progression is not well understood and its value as a tumor biomarker has not been fully elucidated. In the current study, the authors presented evidence supporting the theory that Hsp60 has potential as a biomarker as well as a therapeutic target in patients with large bowel cancer.

Multiple food hypersensitivity as a cause of refractory chronic constipation in adults

Chronic constipation that is unresponsive to laxative treatment is a severe illness, but children unresponsive to laxatives have been successfully treated with an elimination diet. We report the first cases of refractory chronic constipation caused by food hypersensitivity in adults. Four patients with refractory constipation who were unresponsive to high doses of laxatives were put on an oligo-antigenic diet and underwent successive double-blind, placebo-controlled, food challenges (DBPFC). Routine laboratory tests, immunological assays, colonoscopy, esophago-gastroduodenoscopy and rectal and duodenal histology were performed. While on an elimination diet, bowel habits normalized in all patients and a DBPFC challenge triggered the reappearance of constipation. In comparison with another 13 patients with refractory constipation unresponsive to the elimination diet, observed over the same period, the patients with food-hypersensitivity-related constipation had the following characteristics: longer duration of illness (p<0.03), lower body mass index (p<0.03), higher frequency of self-reported food intolerance (p<0.01), higher frequency of nocturnal abdominal pain and anal itching (p<0.01). In patients with food hypersensitivity, hemoglobin concentrations and peripheral leukocytes were lower than those in controls (p<0.03). The duodenal and rectal mucosa histology showed lymphocyte and eosinophil infiltration, and the duodenal villi were flattened in two cases. In adult patients, refractory chronic constipation may be caused by food hypersensitivity and an elimination diet is effective in these subjects.

Hsp10: anatomic distribution, functions, and involvement in human disease

There is growing evidence that molecular chaperones/heat shock proteins are involved in the pathogenesis of a number of human diseases, known as chaperonopathies. A better molecular understanding of the pathogenetic mechanisms is essential for addressing new strategies in diagnostics, therapeutics and clinical management of chaperonopathies, including those in which Hsp10 is involved. This chaperonin has been studied for a long time as a member of the mitochondrial protein-folding machine. However, although in normal cells Hsp10 is mainly localized in the mitochondrial matrix, it has also been found during and after stress in other subcellular compartments, such as cytosol, vesicles and secretory granules, alone or in combination with other proteins. In these extramitochondrial locales, Hsp10 plays an active role in cell signalling. For example, cancer cells often show altered levels of Hsp10, compared to normal cells. Hsp10 may also be found in the extracellular space and in the bloodstream, with a possible immunomodulatory activity. This minireview focuses on some studies to date on the involvement of Hsp10 in human disease pathogenesis.

Familial hypobetalipoproteinemia due to apolipoprotein B R463W mutation causes intestinal fat accumulation and low postprandial lipemia

OBJECTIVE Familial hypobetalipoproteinemia (FHBL) is characterized by inherited low plasma levels of apolipoprotein B (apoB)-containing lipoproteins. In this paper we investigated whether the already described APOB R463W missense mutation, a FHBL mutation able to impair the activity of microsomal triglyceride transfer protein (MTP), may cause intestinal fat accumulation and reduced postprandial lipemia. METHODS Four out of five probands harboring APOB R463W mutation were compared with six healthy controls and six patients with celiac disease (CD). An oral fat load supplemented with retinyl palmitate (RP) was administered and a gastro-duodenal endoscopy with biopsy was performed. RESULTS Plasma triglyceride area under curves was significantly reduced in FHBL probands compared to controls and CD patients; the proportion of absorbed RP was similar to that of CD patients. Only the intestinal biopsies of FHBL patients showed lipids accumulating within the duodenal mucosa. CONCLUSIONS FHBL due to R463W apoB mutation is a cause of intestinal fat accumulation and postprandial lipid absorption impairment.

Clinical symptoms in celiac patients on a gluten-free diet

Objective. Persistent villous atrophy in patients with celiac disease (CD) on a gluten-free diet (GFD) is reported with increasing frequency. The aim of this study was to evaluate a possible association between persistent damage of the villi and “atypical” gastrointestinal symptoms in CD patients on a GFD. Material and methods. Sixty-nine CD patients on a GFD were divided into two groups: Group A included 42 patients (6 M, 36 F, age range 17–62 years) undergoing esophagogastroduodenoscopies (EGDs) due to the presence of symptoms; Group B included 27 control patients (6 M, 21 F, age range 24–71 years) who were asymptomatic at the time of the study. Both groups underwent EGDs and a duodenal histologic study. Results. Persistent endoscopic lesions were more frequent in Group A (30/42) than in Group B (12/27; p=0.01). Villous atrophy was significantly more frequent in Group A than in Group B: 85% versus 33% (p<0.0001; odds ratio (OR)=12; 95% CI 3.7–38.9). Gastrointestinal symptoms in the Group A patients were different from those present at CD diagnosis: anemia/diarrhea/weight loss in 6 cases; gastroesophageal reflux disease (GERD)-like symptoms in 12 cases; abdominal pain/constipation in 24 cases. In Group A there was no difference in gender distribution, age and duration of GFD between subjects with normal villi and those with persistent partial villous atrophy. Patients with persistent symptoms showed a higher intraepithelial eosinophil count (p=0.005) than the asymptomatic patients (p=0.01). Conclusions. Persistent intestinal villous atrophy in CD patients on a GFD is associated with gastrointestinal symptoms considered “atypical” for CD and not present at CD diagnosis.

Endoscopic Resection of a Large Colonic Lipoma: Case Report and Review of Literature

Colonic lipomas are uncommon, benign, submucosal adipose tumors that are usually asymptomatic. Large lipomas can cause symptoms such as constipation, abdominal pain, rectal bleeding and intussusception. We report the case of a 60-year-old man with a history of lower abdominal pain and pseudoobstructive symptoms. Colonoscopy revealed a large polypoid sessile lesion in the sigma. We used a standardized technique of polypectomy, preceded by submucosal injection of dilute 5 ml polygelin with epinephrine 1:10,000 solution, to fully resect large colonic lipomas. The lipoma size was 3.5 cm. No bleeding or perforation developed. Histology showed the polyp to be a submucosul lipoma. On follow-up, there was no residual lesion. Colonic lipomas larger than 2 cm can be safely and efficaciously removed using electrosurgical snare polypectomy technique. The technique of submucosal injection before resection and using an electrocautery snare appears to be safe and reduces the risk of perforation reported in the literature.

Herpes simplex esophagitis in immunocompetent host: a case report.

Introduction. Herpes simplex esophagitis is well recognized in immunosuppressed subjects, but it is infrequent in immunocompetent patients. We present a case of HSE in a 53-year-old healthy man. Materials and Methods. The patient was admitted with dysphagia, odynophagia, and retrosternal chest pain. An esophagogastroduodenoscopy revealed minute erosive area in distal esophagus and biopsies confirmed esophagitis and findings characteristic of Herpes Simplex Virus infection. Results. The patients was treated with high dose of protonpump inhibitor, sucralfate, and acyclovir, orally, with rapid resolution of symptoms. Discussion. HSV type I is the second most common cause of infectious esophagitis. The majority of symptomatic immunocompetent patients with HSE will present with an acute onset of esophagitis. Endoscopic biopsies from the ulcer edges should be obtained for both histopathology and viral culture. In immunocompetent host, HSE is generally a self-limited condition. Conclusions. HSE should be suspected in case of esophagitis without evident cause, even if the patient is immunocompetent. When the diagnosis of HSE is confirmed, careful history and assessment for an immune disorder such as HIV infection is crucial, to look for underlying immune deficiency.