Liver HLA-G expression is associated with multiple clinical and histopathological forms of chronic hepatitis B virus infection

As the mechanisms leading to the persistence of hepatitis B virus (HBV) infection are poorly understood and as the histocompatibility leucocyte antigen (HLA)-G is well described as a tolerogenic molecule, we evaluated HLA-G expression in 74 specimens of HBV liver biopsies and in 10 specimens obtained from previously healthy cadaver liver donors. HBV specimens were reviewed and classified by the METAVIR score, and HLA-G expression was assessed by immunohistochemistry. No HLA-G expression was observed in control hepatocytes. In contrast, 57 (77%) of 74 HBV specimens showed soluble and membrane-bound HLA-G expression in hepatocytes, biliary epithelial cells or both. No associations between the intensity of HLA-G expression and patient age or gender, HBeAg status, severity of liver fibrosis, and grade of histological findings were observed. Although significance was not reached (P = 0.180), patients exhibiting HLA-G expression presented a higher median HBV DNA viral load (105 copies/mL) than those who did not express HLA-G (103.7 copies/mL). These results indicate that HLA-G is expressed in most cases of chronic HBV infection in all stages and may play a role in the persistency of HBV infection.

Stapled haemorrhoidopexy transiently decreases rectal compliance and sensitivity

Aim Stapled haemorrhoidopexy may damage the anorectal musculature and its sensorimotor function. Most studies have not used a barostat for the measurement of compliance. This study aimed to investigate the effect of stapled haemorrhoidopexy on rectal compliance and sensitivity. Method After Ethical Committee approval, we studied 10 male patients (mean age 33.8 years) with third- or fourth-degree haemorrhoids. Rectal compliance and sensitivity were measured with a 600-ml bag and an electronic barostat. Volunteers were submitted to two consecutive rectal distension protocols, including continuous distension at 2, 4 and 6 months after stapled haemorrhoidopexy. Intraluminal volume and pressure were recorded, including the first rectal sensation, desire to defecate and onset of rectal pain. Another group of 10 male control patients (mean age 24.9 years) with pilonidal sinus and no haemorrhoids was also included in the study. Results Two months after stapled haemorrhoidopexy, rectal compliance decreased (7.1 +/- 0.2 vs 5.3 +/- 0.1, 6.4 +/- 0.1 vs 5.1 +/- 0.1 and 5.6 +/- 0.2 vs 4.7 +/- 0.1 ml/mmHg for first rectal sensation, desire to defecate and rectal pain, respectively; P < 0.05). The sensitivity threshold volume did not change for the first sensation but decreased significantly for the desier to defecate and pain (p < 0.05) (116.8 +/- 13.8 vs 148.4 +/- 14.61, 251.1 +/- 8.9 vs 185.8 +/- 8.6 and 293.3 +/- 16.6 vs 221.2 +/- 6.0 ml for first rectal sensation, desire to defecate and rectal pain, respectively). Four and 6 months after surgery, rectal compliance and sensitivity returned to levels similar to those in the basal period. Muscle tissue was found in only three of the 10 resected doughnuts. Controls remained without any change in rectal compliance and sensitivity. Conclusion Stapled haemorrhoidopexy transiently decreases rectal compliance and sensitivity threshold in young male patients.

Validation of ACB in vitro and in vivo as a biomagnetic method for measuring stomach contraction

Background The aim of this study was to validate a biomagnetic method (alternate current biosusceptometry, ACB) for monitoring gastric wall contractions in rats. Methods In vitro data were obtained to establish the relationship between ACB and the strain-gauge (SG) signal amplitude. In vivo experiments were performed in pentobarbital-anesthetized rats with SG and magnetic markers previously implanted under the gastric serosa or after ingestion of magnetic material. Gastric motility was quantified from the tracing amplitudes and frequency profiles obtained by Fast Fourier Transform. Key Results The correlation between in vitro signal amplitudes was strong (R = 0.989). The temporal cross-correlation coefficient between the ACB and SG signal amplitude was higher (P < 0.0001) in the postprandial (88.3 +/- 9.1 V) than in the fasting state (31.0 +/- 16.9 V). Irregular signal profiles, low contraction amplitudes, and smaller signal-to-noise ratios explained the poor correlation between techniques for fasting-state recordings. When a magnetic material was ingested, there was also strong correlation in the frequency and signal amplitude and a small phase-difference between the techniques. The contraction frequencies using ACB were 0.068 +/- 0.007 Hz (postprandial) and 0.058 +/- 0.007 Hz (fasting) (P < 0.002) and those using SG were 0.066 +/- 0.006 Hz (postprandial) and 0.059 +/- 0.008 Hz (fasting) (P < 0.005). Conclusions & Inferences In summary, ACB is reliable for monitoring gastric wall contractions using both implanted and ingested magnetic materials, and may serve as an accurate and sensitive technique for gastrointestinal motility studies.

The H63D genetic variant of the HFE gene is independently associated with the virological response to interferon and ribavirin therapy in chronic hepatitis C

Background Conflicting results have been reported in studies evaluating the relationship between serum markers of iron overload, liver iron deposits, and HFE mutations (C282Y and H63D) in chronic hepatitis C patients, and also their impact on the response to therapy in these patients. Aim To evaluate the role of HFE mutations in the severity of liver disease and in the response to therapy in chronic hepatitis C. Methods Two hundred and sixty-four hepatitis C patients treated with standard interferon and ribavirin were divided into two groups according to type of antiviral response: sustained virological response (SVR) and nonresponse or relapse. We evaluated the relationship between HFE mutation and the type of antiviral response, clinical data, biochemical tests, liver histopathology, virological data, and HFE mutations. Results Of the 264 patients, 88 (32.1%) had SVR whereas 67.9% had nonresponse or relapse. Liver iron deposits were observed in 49.2% of the patients. The factors associated with SVR were hepatitis C virus genotype 2 or 3, transferrin saturation value of 45% or less, and detection of the H63D mutation. HFE mutation was more frequent in patients with iron deposits, but without association with serum iron biochemistry or severity of liver disease. Steatosis was more frequent in patients with liver iron deposits. Conclusion The H63D mutation was an independent factor associated with SVR in chronic hepatitis C patients, as also were hepatitis C virus genotype 2 or 3 and transferrin saturation value of 45% or less. Moreover, the H63D mutation was associated with liver iron deposits. Eur J Gastroenterol Hepatol 22: 1204-1210 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Advantages and Pitfalls of the Polymerase Chain Reaction in the Diagnosis of Esophageal Ulcers in AIDS Patients

HIV-1-infected patients frequently have opportunistic esophageal infections which, when associated with severe immunodeficiency, can be attributed to unusual pathogens. The clinical presentation of several esophageal diseases is similar and the best method for a specific diagnosis of these patients has not been well defined. To evaluate the role of the polymerase chain reaction (PCR) in the etiologic definition of esophageal ulcers in HIV-1-infected patients, 96 esophageal biopsies from 79 HIV-1-infected patients were processed by PCR using specific primers for cytomegalovirus (CMV), herpes virus (HSV), human papilloma virus (HPV), HIV-1, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Treponema pallidum, and Haemophilus ducreyi. The PCR results were compared to the histopathologic results. Seventy-nine patients were studied (mean age: 34 years; 62% men; median CD4 + T cell = 103.59 cells/mu l (range 1-795.2 cells/mu l). The most common endoscopic findings were as follows: esophageal candidiasis (37.1%), esophageal ulcers (24.7%), esophagitis (11.2%), and lugol-negative areas (10.1%). The histopathologic findings in the esophageal ulcers (22 biopsies) were non-specific inflammation (31.8%), HSV (36.4%), Candida (13.6%), CMV (13.6%), or HPV disease (4.5%). In the esophageal ulcer biopsies, the PCR results were negative in 27.6% of cases, and positive for HIV (65.5%), CMV (31%), HPV (20.7%), HSV (10.3%), and H. ducreyi (6.9%). The histopathologic examination did not identify a pathogen or identified only Candida in 15 biopsies of esophageal ulcers. PCR was positive in ten (66.7%) and negative in five (33.3%) of these biopsies (idiopathic ulcers). PCR detected: HIV (53.3%), CMV (20%), HPV (13.3%), and H. ducreyi (6,7%). PCR detected more etiologic agents in esophageal ulcers than histopathology and was able to detect unusual pathogens. On the other hand, sometimes more than one pathogen was detected in the esophageal ulcers, making it difficult to reach an accurate diagnosis. This finding indicates the need for more studies to evaluate the benefit of this method in the routine evaluation of esophageal ulcer biopsies in HIV-1-infected patients.

Evaluation of hepatobiliary excretion and enterobiliary reflux in rats with biliary obstruction submitted to bilioduodenal or biliojejunal anastomosis

Bilioduodenal and biliojejunal anastomoses are effective for the treatment of biliary obstruction. The objective of this study was to compare the effects of these anastomoses on hepatobiliary excretion and enterobiliary reflux. Enterobiliary reflux and biliary excretion were evaluated respectively after oral administration of technetium (Tc-99m) in combination with sodium phytate and intravenous infusion of Tc-99m with diisopropyl-iminodiacetic acid. Enterobiliary reflux occurred to an equal degree in the bilioduodenal and biliojejunal groups. Maximum hepatic activity time (T-max) and radiotracer clearance half-time (T-1/2) were similar in both groups. However, when compared with that found for the sham-operated group, T-max, and T-1/2 were higher in the biliojejunal group (P = 0.02 and P = 0.01, respectively). Histopathological analysis showed marked reduction in ductal proliferation in both groups. These data undermine the theoretical advantages attributed to biliojejunal anastomosis and further the understanding of the pathophysiology of cholangitis that occurs even with patent anastomosis.

Effect of bolus volume on proximal esophageal contractions of patients with Chagas` disease and patients with idiopathic achalasia

Chagas` disease and idiopathic achalasia patients have similar impairment of distal esophageal motility. In Chagas` disease, the contractions occurring in the distal esophageal body are similar after wet or dry swallows. Our aim in this investigation was to evaluate the effect of wet swallows and dry swallows on proximal esophageal contractions of patients with Chagas` disease and with idiopathic achalasia. We studied 49 patients with Chagas` disease, 25 patients with idiopathic achalasia, and 33 normal volunteers. We recorded by the manometric method with continuous water perfusion the pharyngeal contractions 1 cm above the upper esophageal sphincter and the proximal esophageal contractions 5 cm from the pharyngeal recording point. Each subject performed in duplicate swallows of 3-mL and 6-mL boluses of water and dry swallows. We measured the time between the onset of pharyngeal contractions and the onset of proximal esophageal contractions (pharyngeal-esophageal time [ PET]), and the amplitude, duration, and area under the curve (AUC) of proximal esophageal contractions. Patients with Chagas` disease and with achalasia had longer PET, lower esophageal proximal contraction amplitude, and lower AUC than controls (P <= 0.02). In Chagas` disease, wet swallows caused shorter PET, higher amplitude, and higher AUC than dry swallows (P <= 0.03). There was no difference between swallows of 3- or 6-mL boluses. There was no difference between patients with Chagas` disease and with idiopathic achalasia. We conclude that patients with Chagas` disease and with idiopathic achalasia have a delay in the proximal esophageal response and lower amplitude of the proximal esophageal contractions.

Effects of Ischemia and Reperfusion on P2X(2) Receptor Expressing Neurons of the Rat Ileum Enteric Nervous System

Purpose We investigated the effects of ischemia/reperfusion in the intestine (I/R-i) on purine receptor P2X(2)-immunoreactive (IR) neurons of the rat ileum. Methods The superior mesenteric artery was occluded for 45 min with an atraumatic vascular clamp and animals were sacrificed 4 h later. Neurons of the myenteric and submucosal plexuses were evaluated for immunoreactivity against the P2X(2) receptor, nitric oxide synthase (NOS), choline acetyl transferase (ChAT), calbindin, and calretinin. Results Following I/R-i, we observed a decrease in P2X(2) receptor immunoreactivity in the cytoplasm and surface membranes of neurons of the myenteric and submucosal plexuses. These studies also revealed an absence of calbindin-positive neurons in the I/R-i group. In addition, the colocalization of the P2X(2) receptor with NOS, ChAT, and calretinin immunoreactivity in the myenteric plexus was decreased following I/R-i. Likewise, the colocalization between P2X(2) and calretinin in neurons of the submucosal plexus was also reduced. In the I/R-i group, there was a 55.8% decrease in the density of neurons immunoreactive (IR) for the P2X(2) receptor, a 26.4% reduction in NOS-IR neuron, a 25% reduction in ChAT-IR neuron, and a 47% reduction in calretinin-IR neuron. The density of P2X(2) receptor and calretinin-IR neurons also decreased in the submucosal plexus of the I/R-i group. In the myenteric plexus, P2X(2)-IR, NOS-IR, ChAT-IR and calretinin-IR neurons were reduced in size by 50%, 49.7%, 42%, and 33%, respectively, in the I/R-i group; in the submucosal plexus, P2X(2)-IR and calretinin-IR neurons were reduced in size by 56% and 72.6%, respectively. Conclusions These data demonstrate that ischemia/reperfusion of the intestine affects the expression of the P2X(2) receptor in neurons of the myenteric and submucosal plexus, as well as density and size of neurons in this population. Our findings indicate that I/R-i induces changes in P2X(2)-IR enteric neurons that could result in alterations in intestinal motility.

Short-Term Modulation of Extracellular Signal-Regulated Kinase 1/2 and Stress-Activated Protein Kinase/c-Jun NH2-Terminal Kinase in Pancreatic Islets by Glucose and Palmitate Possible Involvement of Ceramide

Objectives: The effect of glucose and palmitate on the phosphorylation of proteins associated with cell growth and survival (extracellular signal-regulated kinase 1/2 [ERK1/2] and stress-activated protein kinase/c-Jun NH2-terminal kinase [SAPK/JNK]) and on the expression of immediate early genes was investigated. Methods: Groups of freshly isolated rat pancreatic islets were incubated in 10-mmol/L glucose with palmitate, LY294002, or fumonisin B1 for the measurement of the phosphorylation and the content of ERK1/2, JNK/SAPK, and v-akt murine thymoma viral oncongene (AKT) (serine 473) by immunoblotting. The expressions of the immediate early genes, c-fos and c-jun, were evaluated by reverse transcription-polymerase chain reaction. Results: Glucose at 10 mmol/L induced ERK1/2 and AKT phosphorylations and decreased SAPK/JNK phosphorylation. Palmitate (0.1 mmol/L) abolished the glucose effect on ERK1/2, AKT, and SAPK/JNK phosphorylations. LY294002 caused a similar effect. The inhibitory effect of palmitate on glucose-induced ERK1/2 and AKT phosphorylation changes was not observed in the presence of fumonisin B1. Glucose increased c-fos and decreased c-jun expressions. Palmitate and LY294002 abolished these latter glucose effects. The presence of fumonisin B1 abolished the effect induced by palmitate on c-jun expression. Conclusions: Our results suggest that short-term changes of mitogen-activated protein kinase and AKT signaling pathways and c-fos and c-jun expressions caused by glucose are abolished by palmitate through phosphatidylinositol 3-kinase inhibition via ceramide synthesis.

Fasting differentially regulates plasma corticosterone-binding globulin, glucocorticoid receptor, and cell cycle in the gastric mucosa of pups and adult rats

Ogias D, de Andrade Sa ER, Kasai A, Moisan M, Alvares EP, Gama P. Fasting differentially regulates plasma corticosterone-binding globulin, glucocorticoid receptor, and cell cycle in the gastric mucosa of pups and adult rats. Am J Physiol Gastrointest Liver Physiol 298: G117-G125, 2010. First published October 15, 2009; doi:10.1152/ajpgi.00245.2009.-The nutritional status influences gastric growth, and interestingly, whereas cell proliferation is stimulated by fasting in suckling rats, it is inhibited in adult animals. Corticosterone takes part in the mechanisms that govern development, and its effects are regulated in particular by corticosterone-binding globulin (CBG) and glucocorticoid receptor (GR). To investigate whether corticosterone activity responds to fasting and how possible changes might control gastric epithelial cell cycle, we evaluated different parameters during the progression of fasting in 18- and 40-day-old rats. Food restriction induced higher corticosterone plasma concentration at both ages, but only in pups did CBG binding increase after short-and long-term treatments. Fasting also increased gastric GR at transcriptional and protein levels, but the effect was more pronounced in 40-day-old animals. Moreover, in pups, GR was observed in the cytoplasm, whereas, in adults, it accumulated in the nucleus after the onset of fasting. Heat shock protein (HSP) 70 and HSP 90 were differentially regulated and might contribute to the stability of GR and to the high cytoplasmic levels in pups and elevated shuttling in adult rats. As for gastric epithelial cell cycle, whereas cyclin D1 and p21 increased during fasting in pups, in adults, cyclin E slowly decreased, concomitant with higher p27. In summary, we demonstrated that corticosterone function is differentially regulated by fasting in 18-and 40-day-old rats, and such variation might attenuate any possible suppressive effects during postnatal development. We suggest that this mechanism could ultimately increase cell proliferation and allow regular gastric growth during adverse nutritional conditions.

Recalled and recorded bowel habits confirm early onset and high frequency of constipation in day-care nursery children

CONTEXT: Mothers recall early-onset constipation in children attending gastroenterology clinics. OBJECTIVES: To study the bowel habit of young children in the community to determine, first, whether early-onset constipation is confirmed in this setting and, second, the agreement between recalled and recorded bowel habit. METHODS:Defecation data of 57 children aged 6.0-40.7 mo were obtained by maternal recall (questionnaire on predominant stool characteristics) and by record (1,934 defecations registered prospectively at home and in the nursery). The bowel habit was classified according to stool frequency and proportion of stool characteristics (soft, hard and/or runny). Two criteria were used to classify recorded data, since the cutoff point for hard stools to identify constipation is undefined in children: predominant criterion and adult criterion, respectively with >50% and >25% of stools with altered consistency. Bowel habit categories were: adequate, constipation, functional diarrhea and "other bowel habit". Nonparametric statistics, and the Kappa index for agreement between recalled and recorded bowel habit, were used. RESULTS: Constipation occurred in 17.5%, 10.5%, 19.3% of the children by recall, the predominant and the adult criteria, respectively. Constipation was the main recalled alteration, vs 12.3% "other bowel habit". Only one child classified as having functional diarrhea (by the adult criterion). Agreement between recalled and recorded bowel habit was fair for constipation, by the predominant and the adult criteria (K = 0.28 and 0.24, respectively), but only slight (K <0.16) for other bowel habit categories. Individual data, however, pointed to a better relationship between recalled constipation and the adult rather than the predominant criterion. CONCLUSIONS: Frequent early-onset constipation was confirmed. Fair agreement between recalled and recorded constipation by the two used criteria indicates that recalled data are quite reliable to detect constipation.

Quadruple therapy with furazolidone for retreatment in patients with peptic ulcer disease

AIM: To establish the efficacy and safety of a 7-d therapeutic regimen using omeprazole, bismuth suticitrate, furazolidone and amoxicillin in patients with peptic ulcer disease who had been previously treated with other therapeutic regimens without success. METHODS: Open cohort study which included patients with peptic ulcer who had previously been treated unsuccessfully with one or more eradication regimens. The therapeutic regimen consisted of 20 mg omeprazole, 240 mg colloidal bismuth subcitrate, 1000 mg amoxicillin, and 200 mg furazolidone, taken twice a day for 7 d. Patients were considered as eradicated when samples taken from the gastric antrum and corpus 12 wk after the end of treatment were negative for Helicobacter pylori (H pylori) (rapid urease test and histology). Safety was determined by the presence of adverse effects. RESULTS: Fifty-one patients were enrolled. The eradication rate was 68.8% (31/45). Adverse effects were reported by 31.4% of the patients, and these were usually considered to be slight or moderate in the majority of the cases. Three patients had to withdraw from the treatment due to the presence of severe adverse effects. CONCLUSION: The association of bismuth, furazolidone, amoxicillin and a proton-pump inhibitor is a valuable alternative for patients who failed to respond to other eradication regimens. It is an effective, cheap and safe option for salvage therapy of positive patients. (C) 2008 The WJG Press. All rights reserved.

Short-term triple therapy with azithromycin for Helicobacter pylori eradication: Low cost, high compliance, but low efficacy

Background: The Brazilian consensus recommends a short-term treatment course with clarithromycin, amoxicillin and proton-pump inhibitor for the eradication of Helicobacter pylori ( H. pylori). This treatment course has good efficacy, but cannot be afforded by a large part of the population. Azithromycin, amoxicillin and omeprazole are subsidized, for several aims, by the Brazilian federal government. Therefore, a short-term treatment course that uses these drugs is a low-cost one, but its efficacy regarding the bacterium eradication is yet to be demonstrated. The study's purpose was to verify the efficacy of H. pylori eradication in infected patients who presented peptic ulcer disease, using the association of azithromycin, amoxicillin and omeprazole. Methods: Sixty patients with peptic ulcer diagnosed by upper digestive endoscopy and H. pylori infection documented by rapid urease test, histological analysis and urea breath test were treated for six days with a combination of azithromycin 500 mg and omeprazole 20 mg, in a single daily dose, associated with amoxicillin 500 mg 3 times a day. The eradication control was carried out 12 weeks after the treatment by means of the same diagnostic tests. The eradication rates were calculated with 95% confidence interval. Results: The eradication rate was 38% per intention to treat and 41% per protocol. Few adverse effects were observed and treatment compliance was high. Conclusion: Despite its low cost and high compliance, the low eradication rate does not allow the recommendation of the triple therapy with azithromycin as an adequate treatment for H. pylori infection.

A perivascular epithelioid cell tumor of the stomach: An unsuspected diagnosis

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasia and currently well recognized as a distinct entity with characteristic morphological, immunohistochemical and molecular findings. We report a case of PEComa arising in the antrum of a 71-year-old female with melena. The tumor, located predominantly in the submucosa as a well delimited nodule, measured 3.0 cm in diameter and was completely resected, with no evidence of the disease elsewhere. Histologically, it was composed predominantly of eosinophilic epithelioid cells arranged in small nests commonly related to variably sized vessels, with abundant extracellular material, moderate nuclear variation and discrete mitotic activity. No necrosis, angiolymphatic invasion or perineural infiltration was seen. Tumor cells were uniformly positive for vimentin, smooth muscle actin, desmin and melan A. Although unusual, PEComa should be considered in the differential diagnosis of gastric neoplasia with characteristic epithelioid and oncocytic features and prominent vasculature: (C) 2010 Baishideng. All rights reserved.

Role of upper endoscopy in diagnosing opportunistic infections in human immunodeficiency virus-infected patients

Highly active antiretroviral therapy (HAART) has dramatically decreased opportunistic infections (OIs) in human immunodeficiency virus (HIV)-infected patients. However, gastrointestinal disease continues to account for a high proportion of presenting symptoms in these patients. Gastrointestinal symptoms in treated patients who respond to therapy are more likely to the result of drug-induced complications than OI. Endoscopi evaluation of the gastrointestinal tract remains a cornerstone of diagnosis, especially in patients with advanced immunodeficiency, who are at risk for OI. The peripheral blood CD4 lymphocyte count helps to predict the risk of an OI, with the highest risk seen in HIV-infected patients with low CD4 count (< 200 cells/mm(3)). This review provides an update of the role of endoscopy in diagnosing OI in the upper gastrointestinal tract in HIV-infected patients in the era of HAART. (C) 2009 The WJG Press and Baishideng. All rights reserved.