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The role of angiotensin converting enzyme 2 has expanded from regulating the renin angiotensin system to regulating intestinal amino acid homeostasis and the gut microbiome. Recently, angiotensin converting enzyme 2 was identified as a primary receptor for severe acute respiratory syndrome coronaviruses 1 and 2 being expressed in multiple tissues including the luminal surface of the gut. In this brief perspective, we examine the role of angiotensin converting enzyme 2 as the receptor for severe acute respiratory syndrome coronavirus 2 and the impact of coronavirus disease 19 infection on the gut microbiome and on the gut epithelium., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Ghrelin-O-acyltransferase (GOAT) is a membrane-bound enzyme that attaches eight-carbon octanoate to a serine residue in ghrelin and thereby acylates inactive ghrelin to produce active ghrelin. In this study, we investigated the function of GOAT in the intestinal mucosal barrier. The intestinal mucosal barrier prevents harmful substances such as bacteria and endotoxin from entering the other tissues, organs, and blood circulation through the intestinal mucosa. Here, we established 5% dextran sodium sulfate (DSS)-induced colitis in mice and found that the body weight and colon weight were significantly decreased in these mice. Furthermore, increased inflammation and apoptosis were observed in the tissues of DSS-induced colitis mice, with increased expression of tumor necrosis factor-α, interleukin-6, phosphorylation of nuclear factor kappa B-p65 (p-NF-κB-p65), and cleaved caspase-3, and decreased expression of tight junction (TJ) proteins such as zonula occluden-1 and occludin. The knockdown of GOAT significantly attenuated colitis-induced inflammation responses and apoptosis, while GOAT overexpression significantly enhanced the induction of colitis. These results suggest that knockdown of GOAT may attenuate colitis-induced inflammation, ulcers, and fecal occult blood by decreasing the intestinal mucosal permeability via the modulation of inflammatory factors and TJ proteins., (© 2020 International Federation for Cell Biology.)

Prevalence of food allergies in the United States is on the rise. Eosinophils are recruited to the intestinal mucosa in substantial numbers in food allergen-driven gastrointestinal (GI) inflammation. Soluble epoxide hydrolase (sEH) is known to play a pro-inflammatory role during inflammation by metabolizing anti-inflammatory epoxyeicosatrienoic acids (EETs) to pro-inflammatory diols. We investigated the role of sEH in a murine model of food allergy and evaluated the potential therapeutic effect of a highly selective sEH inhibitor (trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]-cyclohexyloxy}-benzoic acid [t-TUCB]). Oral exposure of mice on a soy-free diet to soy protein isolate (SPI) induced expression of intestinal sEH, increased circulating total and antigen-specific IgE levels, and caused significant weight loss. Administration of t-TUCB to SPI-challenged mice inhibited IgE levels and prevented SPI-induced weight loss. Additionally, SPI-induced GI inflammation characterized by increased recruitment of eosinophils and mast cells, elevated eotaxin 1 levels, mucus hypersecretion, and decreased epithelial junction protein expression. In t-TUCB-treated mice, eosinophilia, mast cell recruitment, and mucus secretion were significantly lower than in untreated mice and SPI-induced loss of junction protein expression was prevented to variable levels. sEH expression in eosinophils was induced by inflammatory mediators TNF-α and eotaxin-1. Treatment of eosinophils with t-TUCB significantly inhibited eosinophil migration, an effect that was mirrored by treatment with 11,12-EET, by inhibiting intracellular signaling events such as ERK (1/2) activation and eotaxin-1-induced calcium flux. These studies suggest that sEH induced by soy proteins promotes allergic responses and GI inflammation including eosinophilia and that inhibition of sEH can attenuate these responses., (©2018 Society for Leukocyte Biology.)

Introduction: Acute gastroenteritis (AGE) is one of the most common causes of morbidity and mortality, especially among children from developing countries. Human adenovirus (HAdV) and sapovirus (SaV) are among the agents that cause AGE. The present study aimed to detect and genotype HAdV and SaV in 172 fecal samples from children with AGE, collected during a surveillance study carried out in a low-income community in Belém, Pará, between 1990 and 1992., Methods: HAdV was detected by nested PCR, using primers Hex1deg/Hex2deg and NeHex3deg/NeHex4deg. SaV was assayed by reverse transcription PCR (RT-PCR), nested PCR, and quantitative PCR. The nucleotide sequence was determined by direct cycle sequencing., Results: Overall, 43% (74/172) of samples were positive for HAdV, of which 70.3% (52/74) were sequenced and classified as belonging to five different species, mostly A and F. For SaV, positivity was 5.2% (9/172) and genotypes GI.1, GI.7, GII.1, and GV.2 were detected., Conclusions: The present results reinforce the need for further studies to obtain epidemiological data about the circulation of these viruses in Brazil, especially in the Amazon Region, where data from the early 1990's are scarce. Furthermore, the study describes for the first time the detection of SaV genotypes GI.7 and GV.2 in Brazil, showing that these types circulated in the region more than 25 years ago.

Background: The aim of this study was to investigate the frequency of elevated alanine (ALT) and aspartate aminotransferase (AST) levels in children with rotavirus positive and negative gastroenteritis as well as the average time to normalization of liver enzymes., Methods: Into the study 298 patients with rotavirus positive and 321 patients with rotavirus negative gastroenteritis were enrolled., Results: Mean AST (56.9±2.1 and 40.2±0.9 U/L, respectively, P=0.000) and ALT (33.1±1.7 and 22.4±0.8 U/L, respectively, P=0.000) levels were significantly higher in the rotavirus positive than rotavirus negative patients. Logistic regression analysis showed that rotavirus positivity was significant independent factor for both AST and ALT elevation. Severity of gastroenteritis was another significant independent factor for ALT elevation. The average transaminase normalization time for AST and ALT levels were similar both rotavirus positive and negative groups., Conclusions: Rotavirus positivity and severity of gastroenteritis were independent risk factors for elevated ALT levels in children with gastroenteritis.

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been implicated in the pathogenesis of gastrointestinal diseases, such as rotavirus gastroenteritis (GE). Kinetics of these biomarkers were examined in paired serum samples collected from bacterial enteritis patients with Campylobacter (n = 2) and Salmonella (n = 4) and viral GE patients with rotavirus (n = 27), norovirus (n = 25), and adenovirus (n = 11). At the time of hospital admission, all viral GE patients demonstrated increased MMP-9 and decreased MMP-2 and TIMP-2 serum levels. In contrast to viral GE patients, serum MMP-9 levels were not elevated at the time of hospital admission but elevated at the time of discharge; serum MMP-2 and TIMP-2 levels were decreased both at the time of admission and discharge in bacterial enteritis patients. Interestingly, the kinetics of serum MMP-2, MMP-9, and TIMP-2 levels were similar among the viral GE patients but distinct from bacterial enteritis patients. Thus, the involvement of MMPs and TIMPs in the pathophysiology of gastrointestinal symptoms likely varies depending on the etiological agent. Further studies are required to verify whether the extent of the bacterial enteritis or age of the patients influences these serum biomarkers. J. Med. Virol. 88:1341-1346, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background & Aims: Dual oxidase 2 (DUOX2), a hydrogen-peroxide generator at the apical membrane of gastrointestinal epithelia, is up-regulated in patients with inflammatory bowel disease (IBD) before the onset of inflammation, but little is known about its effects. We investigated the role of DUOX2 in maintaining mucosal immune homeostasis in mice., Methods: We analyzed the regulation of DUOX2 in intestinal tissues of germ-free vs conventional mice, mice given antibiotics or colonized with only segmented filamentous bacteria, mice associated with human microbiota, and mice with deficiencies in interleukin (IL) 23 and IL22 signaling. We performed 16S ribosomal RNA gene quantitative polymerase chain reaction of intestinal mucosa and mesenteric lymph nodes of Duoxa(-/-) mice that lack functional DUOX enzymes. Genes differentially expressed in Duoxa(-/-) mice compared with co-housed wild-type littermates were correlated with gene expression changes in early-stage IBD using gene set enrichment analysis., Results: Colonization of mice with segmented filamentous bacteria up-regulated intestinal expression of DUOX2. DUOX2 regulated redox signaling within mucosa-associated microbes and restricted bacterial access to lymphatic tissues of the mice, thereby reducing microbiota-induced immune responses. Induction of Duox2 transcription by microbial colonization did not require the mucosal cytokines IL17 or IL22, although IL22 increased expression of Duox2. Dysbiotic, but not healthy human microbiota, activated a DUOX2 response in recipient germ-free mice that corresponded to abnormal colonization of the mucosa with distinct populations of microbes. In Duoxa(-/-) mice, abnormalities in ileal mucosal gene expression at homeostasis recapitulated those in patients with mucosal dysbiosis., Conclusions: DUOX2 regulates interactions between the intestinal microbiota and the mucosa to maintain immune homeostasis in mice. Mucosal dysbiosis leads to increased expression of DUOX2, which might be a marker of perturbed mucosal homeostasis in patients with early-stage IBD., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: In inflammatory bowel diseases (IBD) diarrhea can be caused by exacerbation and/or infectious agents. Fecal calprotectin (FC) is a well-established biomarker of intestinal inflammation in IBD. However, its usefulness in depiction of IBD exacerbation from infectious diarrhea is limited. The value of fecal pyruvate kinase isoenzyme type 2 (M2-PK) in this application remains unknown., Aim: To compare the performance of M2-PK and FC in discriminating between diarrhea caused by IBD and infectious agents., Materials and Methods: One hundred three patients were enrolled for the study, including 32 with ulcerative colitis (UC), 21 with Crohn's disease (CD), 29 with acute diarrhea caused by rotavirus (AD-RV), and 21 with acute diarrhea caused by Salmonella enteritidis (AD-SE). M2-PK and FC were measured using ELISA. Areas under receiver operating characteristic curves (AUCs), sensitivities and specificities for both tests in distinguishing between patient subgroups with moderate to severe UC and CD from AD-RV and AD-SE were calculated., Results: Differences in AUCs between M2-PK and FC for distinguishing UC [CD] from AD-RV were -0.06 (p < 0.028) [-0.10 (p < 0.0018)] and for differentiating UC [CD] from AD-SE were 0.03 (NS) [-0.19(p < 0.0011)].M2-PK sensitivities and specificities in distinguishing UC [CD] from AD-RV were 75.0%[71.4%] and 89.7% [89.7%] and for differentiation of UC [CD] from AD-SE were 56.3% [71.4%] and 95.2[57.1%]., Conclusions: The performance of M2-PK in distinguishing between children with moderate-to-severe IBD and patients with infectious gastroenteritis was inferior to FC. Neither test had sensitivity ands pecificity sufficient for everyday clinical application.

Chronic inflammation increases the risk of developing cancer. For example, patients with severe and prolonged inflammatory bowel disease, particularly ulcerative colitis, have a significantly higher risk of developing colorectal cancer. Serine proteases coordinating the coagulation cascade and immune cell proteases play important roles in regulating the inflammatory response through their actions on protease-activated receptors (PAR). PARs and their activating proteases have also been implicated in many cancers, including CRC. Importantly, the actions of proteases could be important for mediating the transition from chronic inflammation to cancer. PAR activation has been shown to have pro-tumourigenic effects including the production of matrix metalloproteinases that can promote tumour cell growth and metastasis, and transactivation of the epidermal growth factor receptor, which is a main target for cancer treatment. Additionally, PAR activation can also result in increased expression of cyclooxygenase (COX)-2, an important enzyme mediating inflammation, resolution, and cancer progression. In this review, we will highlight our current knowledge about the effects of proteases and their receptors on intestinal inflammation and cancer, and explore the potential role of PAR-induced COX-2 on colitis-associated cancer.

Inflammasome-mediated host defenses have been extensively studied in innate immune cells. Whether inflammasomes function for innate defense in intestinal epithelial cells, which represent the first line of defense against enteric pathogens, remains unknown. We observed enhanced Salmonella enterica serovar Typhimurium colonization in the intestinal epithelium of caspase-11-deficient mice, but not at systemic sites. In polarized epithelial monolayers, siRNA-mediated depletion of caspase-4, a human ortholog of caspase-11, also led to increased bacterial colonization. Decreased rates of pyroptotic cell death, a host defense mechanism that extrudes S. Typhimurium-infected cells from the polarized epithelium, accounted for increased pathogen burdens. The caspase-4 inflammasome also governs activation of the proinflammatory cytokine, interleukin (IL)-18, in response to intracellular (S. Typhimurium) and extracellular (enteropathogenic Escherichia coli) enteric pathogens, via intracellular LPS sensing. Therefore, an epithelial cell-intrinsic noncanonical inflammasome plays a critical role in antimicrobial defense at the intestinal mucosal surface., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Intestinal infections by attaching and effacing (A/E) bacterial pathogens cause severe colitis and bloody diarrhea. Although p38α in intestinal epithelial cells (IEC) plays an important role in promoting protection against A/E bacteria by regulating T cell recruitment, its impact on immune responses remains unclear. In this study, we show that activation of p38α in T cells is critical for the clearance of the A/E pathogen Citrobacter rodentium. Mice deficient of p38α in T cells, but not in macrophages or dendritic cells, were impaired in clearing C. rodentium. Expression of inflammatory cytokines such as IFN-γ by p38α-deficient T cells was reduced, which further reduced the expression of inflammatory cytokines, chemokines, and antimicrobial peptide by IECs and led to reduced infiltration of T cells into the infected colon. Administration of IFN-γ activated the mucosal immunity to C. rodentium infection by increasing the expression of inflammation genes and the recruitment of T cells to the site of infection. Thus, p38α contributes to host defense against A/E pathogen infection by regulating the expression of inflammatory cytokines that activate host defense pathways in IECs.

Background: There are no studies on clinically significant transaminase elevation due to rotavirus gastroenteritis in the literature. Also, there are significant discrepancies among previous studies regarding the prevalence of increased serum transaminase levels in rotavirus infection., Methods: Patients investigated for rotavirus by stool antigen testing, who were followed between January 2005 and May 2012, were retrospectively enrolled in this study. Patients were divided into 2 groups according to their rotavirus results: rotavirus-positive acute gastroenteritis (RPAG) and rotavirus-negative acute gastroenteritis (RNAG) groups., Results: A total of 4317 children who presented with acute gastroenteritis were assessed. The study was completed with 642 patients who met the inclusion criteria. In the RPAG group (n = 272), elevated alanine aminotransferase (ALT) was found in 42 (15.4%) patients and elevated aspartate aminotransferase (AST) in 69 (25.4%), while in the RNAG group (n = 370), these numbers were 25 (6.8%) and 44 (11.9%), respectively. The elevated ALT and AST levels were found to be significantly higher in the RPAG group than in the RNAG group (both p < 0.001). The prevalence of elevated transaminase levels was found to be similar with respect to gastroenteritis severity score (p > 0.05). The high serum transaminase levels normalized uneventfully in all patients in the RPAG and RNAG groups during follow-up., Conclusions: In this study, our results clearly signify a liver influence in rotavirus infections. Therefore, rotavirus infections should be kept in mind when evaluating the aetiology of transaminase elevation in patients with acute gastroenteritis.

Mushroom toxicosis is rarely diagnosed in dogs and is poorly reported in the veterinary literature. This report suggests that mushroom toxicosis is a potentially under-diagnosed condition in first opinion practice in the UK. Nine dogs with clinical signs consistent with mushroom toxicosis were identified from the records of an out-of-hours emergency service between August 2010 and January 2011. Four dogs were later excluded because of clinical inconsistencies. Clinical signs included acute profuse ptyalism (5/5), diarrhoea (5/5), vomiting (4/5), hypovolaemia (4/5), stuporous (3/5) or obtunded mentation (1/5), miosis (2/5) and hypothermia (2/5). Serum lipase activity was elevated in 4/4 dogs; canine-specific pancreatic lipase was elevated in the remaining dog. Four dogs recovered with aggressive intravenous fluid therapy, analgesia and supportive care; the remaining dog was euthanased due to severe clinical signs and financial constraints. Mushroom toxicosis is an important differential diagnosis for acute gastroenteritis and one possible cause of some cases of "Seasonal Canine Illness". Affected dogs may demonstrate elevated pancreatic enzymes and mushroom toxicosis should be considered in cases of elevated lipase or abnormal semi-quantitative canine-specific pancreatic lipase activities., (© 2013 British Small Animal Veterinary Association.)

Alimentary tract (AT) mucositis is a serious and debilitating side-effect of cancer therapy primarily characterized by damage of the mucous membranes throughout the AT. It is well established that this damage is a result of up-regulation of stress response genes and pro-inflammatory cytokines. Matrix metalloproteinases (MMPs) have been shown to function in several of the pathways known to be up-regulated in mucositis and play a key role in tissue injury and inflammation in many gastrointestinal disorders. This study aims to characterize the expression of multiple MMPs including MMP-1, -2, -3, -9 and -12 and their inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and -2, in a rat model of irinotecan-induced mucositis. Dark agouti rats were administered a single 200 mg/kg intraperitoneal dose of irinotecan and killed at 1, 6, 24, 48, 72, 96 and 144 h following treatment. Hematoxylin and eosin staining, immunohistochemistry and realtime polymerase chain reaction were used to assess histopathological damage and MMP expression in the jejunum and colon. Marked histopathological evidence of mucositis was observed in the jejunum and colon as early as six hours following irinotecan treatment. A significant alteration in both gene expression and tissue levels of MMPs and TIMPs was noted following irinotecan. The increase in MMP-2, -3, -9 and -12 levels was associated with inflammatory infiltrate and maximum tissue damage. In contrast, MMP-1 expression correlated with tissue restitution. TIMP-1 and -2 levels were significantly altered in the jejunum following irinotecan. The augmentation in the expression profiles of MMPs and their inhibitors correlated with histopathological alterations observed in the tissue following irinotecan. This prompts the consideration of MMPs as possible mediators of chemotherapy-induced mucositis.

Enterocytes exist in close association with tissue macrophages, whose activation during inflammatory processes leads to the release of nitric oxide (NO). Repair from mucosal injury requires the migration of enterocytes into the mucosal defect, a process that requires connexin43 (Cx43)-mediated gap junction communication between adjacent enterocytes. Enterocyte migration is inhibited during inflammatory conditions including necrotizing enterocolitis, in part, through impaired gap junction communication. We now hypothesize that activated macrophages inhibit gap junctions of adjacent enterocytes and seek to determine whether NO release from macrophages was involved. Using a coculture system of enterocytes and macrophages, we now demonstrate that "activation" of macrophages with lipopolysaccharide and interferon reduces the phosphorylation of Cx43 in adjacent enterocytes, an event known to inhibit gap junction communication. The effects of macrophages on enterocyte gap junctions could be reversed by treatment of macrophages with the inducible nitric oxide synthase (iNOS) inhibitor l-Lysine omega-acetamidine hydrochloride (l-NIL) and by incubation with macrophages from iNOS(-/-) mice, implicating NO in the process. Activated macrophages also caused a NO-dependent redistribution of connexin43 in adjacent enterocytes from the cell surface to an intracellular location, further suggesting NO release may inhibit gap junction function. Treatment of enterocytes with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) markedly inhibited gap junction communication as determined using single cell microinjection of the gap junction tracer Lucifer yellow. Strikingly, activated macrophages inhibited enterocyte migration into a scraped wound, which was reversed by l-NIL pretreatment. These results implicate enterocyte gap junctions as a target of the NO-mediated effects of macrophages during intestinal inflammation, particularly where enterocyte migration is impaired.

Rotavirus is one of the leading causes of acute gastroenteritis among children. While clinical complaints are generally intestinal including vomiting and diarrhea, there is evidence to suggest that disease outside the gastrointestinal tract occurs. This study examines the frequency of hepatic transaminase elevation in children with rotavirus gastroenteritis. Patients identified with rotavirus gastroenteritis by stool antigen testing between November 2005 and March 2006 had available serum analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, direct bilirubin, and creatinine phoshosphokinase (CPK). Chart review was conducted to identify patients with possible liver injury unrelated to rotavirus. Among the 92 patients identified with rotavirus during the study period, 75 had serum specimens available for testing. Fifteen patients (20%) had elevated ALT and AST, including one patient with an increase in AST, ALT, alkaline phosphatase, and total and direct bilirubin. The mean ALT elevation was 56 IU/L (range, 44 to 114 IU/L), and the mean AST elevation was 80 IU/L (range, 57 to 126 IU/L). Fifty-three patients (71%) had an increase in AST alone, and three patients (4%) had an increase in AST and alkaline phosphatase. The mean AST values in these groups were 61 IU/L (range, 42 to 110 IU/L) and 79 IU/L (range, 59 to 96 IU/L), respectively. In conclusion, rotavirus commonly causes elevation of liver transaminases.

The gastrointestinal (GI) tract is exposed to a large array of proteases, under both physiological and pathophysiological conditions. The discovery of G protein-coupled receptors activated by proteases, the protease-activated receptors (PARs), has highlighted new signaling functions for proteases in the GI tract, particularly in the domains of inflammation and pain mechanisms. Activation of PARs by selective peptidic agonists in the intestine or the pancreas leads to inflammatory events and changes in visceral nociception, suggesting that PARs could be involved in the modulation of visceral pain and inflammation. PARs are present in most of the cells that are potentially actors in the generation of irritable bowel syndrome (IBS) symptoms. Activation of PARs interferes with several pathophysiological factors that are involved in the generation of IBS symptoms, such as altered motility patterns, inflammatory mediator release, altered epithelial functions (immune, permeability and secretory) and altered visceral nociceptive functions. Although definitive studies using genetically modified animals, and, when available, pharmacological tools, in different IBS and inflammatory models have not yet confirmed a role for PARs in those pathologies, PARs appear as promising targets for therapeutic intervention in visceral pain and inflammation processes.

The authors advocate introduction of the respiratory test into clinical practice, show its advantages over other methods of Hp diagnosis and the ability to diagnose non-invasively other gastrointestinal diseases especially in advanced infection primarily in viral hepatitides, HIV infections. The method is safe and comfortable.

Listeria monocytogenes is a bacterial pathogen causing severe food-borne infections in humans and animals. It can sense and adapt to a variety of harsh microenvironments outside as well as inside the host. Once ingested by a mammalian host, the bacterial pathogen reaches the intestinal lumen, where it encounters bile salts which, in addition to their role in digestion, have antimicrobial activity. Comparison of the L. monocytogenes and Listeria innocua genomes has revealed the presence of an L. monocytogenes-specific putative gene encoding a bile salt hydrolase (BSH). Here, we show that the bsh gene encodes a functional intracellular enzyme in all pathogenic Listeria species. The bsh gene is positively regulated by PrfA, the transcriptional activator of known L. monocytogenes virulence genes. Moreover, BSH activity increases at low oxygen concentration. Deletion of bsh results in decreased resistance to bile in vitro, reduced bacterial faecal carriage after oral infection of the guinea-pigs, reduced virulence and liver colonization after intravenous inoculation of mice. Taken together, these results demonstrate that BSH is a novel PrfA-regulated L. monocytogenes virulence factor involved in the intestinal and hepatic phases of listeriosis.

Gene expression of key enzymes in 2 antiviral pathways (ribonuclease latent [RNase L] and RNA-regulated protein kinase [PKR]) was compared in 22 patients with chronic fatigue syndrome (CFS), 10 patients with acute gastroenteritis, and 21 healthy volunteers. Pathway activation in the group of patients with infections differed significantly from that of the other 2 groups, in whom there was no evidence of upregulation. Therefore, assay of activation is unlikely to provide the basis for a diagnostic test for CFS.

Rotavirus and adenovirus antigens in feces from 77 cases of gastroenteritis in pediatric patients were examined. Mitochondrial enzymes, mitochondrial creatine kinase(mCK), mitochondrial aspartate amino-transferase(mAST) and mitochondrial malate dehydrogenase(mMDH) activities in their sera were also measured and compared with the results of rotavirus and adenovirus antigens in the feces. Thirty-one cases were rotavirus antigen-negative(rota-negative)/adenovirus antigen-negative(adeno-negative), 5 were rota-negative/adenovirus antigen-positive(adeno-positive), 40 were rotavirus antigen-positive(rota-positive)/adeno-negative, and only one case showed positive for both antigens. The mean activities of these three enzymes were compared among 3 groups except one both positive case mentioned above and control group(n = 105) by Mann-Whitney U-test. The serum mCK activity was significantly higher in rota-positive/adeno-negative patients than in other groups(p < 0.01). On the other hand, no significant differences were observed for mAST and mMDH activities among any groups. It is suggested that these phenomena are caused by the differences of localization of these enzymes in mitochondria, that mCK is located the outer surface of inner membrane of mitochondria, and mAST and mMDH are located on the inner surface. The difference of serum mCK activity between rotavirus infection and adenovirus infection suggests that intestinal epithelial cell injury by rotavirus is stronger than that by adenovirus.

The objective of this study was to investigate the relationship between serum mitochondrial creatine kinase(mCK) and rotavirus gastroenteritis in pediatric patients. Stool and serum specimens were simultaneously collected from 45 patients(25 males and 20 females) with suspected rotavirus gastroenteritis from January to December 1998. Stool specimens were tested by rotavirus latex agglutination assay. Fourteen patients(10 males, 4 females) were proved as positive, and peak season was in winter and early spring(7 positive cases in March). Six of the 14 were younger than one and 7 were between one and two. Total serum CK activity was measured by The Japan Society of Clinical Chemistry (JSCC) recommended method, and mCK activity was calculated from mCK fraction % obtained by CK isoenzyme electrophoresis. Patients' mCK activities were as follows, rotavirus antigen positive patients(n = 14): 60.0 +/- 20.6 U/l and rotavirus antigen negative patients(n = 31): 7.2 +/- 5.5 U/l. Significant difference was observed between rotavirus antigen positive group and rotavirus antigen negative group(p < 0.01), and control children group(n = 105): 7.1 +/- 2.9 U/l, (p < 0.01). The clinical implications and mechanisms of increased serum mCK activity are unclear. It is known that histological study of the small intestine from rotavirus gastroenteritis patients reveal shortened villi and mononuclear cell infiltration of the lamia propria; electron microscopy shows mitochondrial swelling and sparse irregular microvilli. Elevated serum mCK level of rotavirus gastroenteritis patient may therefore reflect diffused intestinal epithelial cell damage.

Objective: In children with coeliac disease, the ingestion of gluten causes small intestinal inflammation and a clinical picture of malabsorption, weight reduction and short stature. Decreased alkaline phosphatase (ALP) during gluten challenge was found in a previous study. ALP is a marker of bone formation and ALP activities are correlated with growth velocity. The aim of this study was to characterise the previously observed decrease of total ALP by investigating three specific bone ALP isoforms (bone/intestinal, B1 and B2) and three specific liver ALP isoforms (L1, L2 and L3) and, moreover, to correlate these ALP isoforms with other growth factors and growth markers. In addition, we also studied the association with possible weight changes, small intestinal mucosa inflammation, sex, age and gluten dose during gluten challenge., Materials and Methods: Bone and liver ALP isoforms, IGF-I, IGF-binding protein (IGFBP)-3 and serum cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were measured together with change in weight and small intestinal mucosa histopathology in 54 children with earlier enteropathy who participated in a 4-week gluten challenge., Results: We observed a decreased total ALP activity after 4 weeks of gluten challenge, 7.8+/-1.8 to 6.5+/-1.7 microkat/l (means +/- s.d.), which was mainly due to a reduction of the bone ALP isoforms. The sum of all three bone ALP isoforms decreased from 6.3+/-1.7 to 5.1+/-1.6 microkat/l. The decreased activities of the bone ALP isoforms correlated with the observed reductions of IGF-I (r=0.74, P<0.001), IGFBP-3 (r=0.51, P<0.001) and ICTP (r=0.57, P<0.001). The decrease of the growth factors and growth markers correlated with weight reduction, but when influences from the change in weight were adjusted for, the partial correlation of the small intestinal mucosa inflammation was significant for IGF-I (r=-0.56, P<0.001) and IGFBP-3 (r=-0.55, P<0.001)., Conclusion: The decrease of total ALP was due to a reduction of bone ALP. The decrease of IGF-I and IGFBP-3 was independently correlated with weight change and small intestinal inflammation.

Background: Gastrointestinal tumors often contain high amounts of the detoxification enzyme glutathione S-transferase P1-1 (GSTP1-1). Elevated levels of GSTP1-1 were found in serum and plasma from most patients with gastrointestinal tumors. The authors evaluated the role of GSTP1-1 as a plasma tumor marker in patients with gastrointestinal tumors., Methods: A sensitive and specific sandwich enzyme-linked immunoadsorbent assay for quantification of GSTP1-1 in human plasma was developed., Results: GSTP1-1 levels in serum samples from 10 healthy controls were significantly (P < 0.0001) higher than in corresponding ethylenediaminetetraacetic acid (EDTA) plasma and varied with the type of blood collection tube used. Refrigeration or delayed centrifugation of blood collected in plain EDTA tubes resulted in spuriously high plasma GSTP1-1 levels. Therefore, all plasma samples were collected in silicone-coated EDTA tubes. The distribution of plasma GSTP1-1 levels in 230 blood donors was nearly normalized by logarithmic transformation and an upper normal reference level of 21.8 microg/L was calculated. Males had significantly higher (P < 0.0001) plasma GSTP1-1 levels than females and a significant increase (P < 0.004) in plasma GSTP1-1 with age was noted. In only 20 of 55 patients (36%) with gastrointestinal tumors was the plasma GSTP1-1 level above the upper normal reference limit. No significant decrease in plasma GSTP1-1 was noted in matched pairs of plasma samples collected from 17 patients before and at least 2 weeks after resection of the tumor., Conclusions: The GSTP1-1 level in serum and plasma depends on the materials and methods used to collect the samples. Only 36% of the patients with gastrointestinal tumors had elevated plasma GSTP1-1 levels that did not decrease after resection of the tumor. These findings argue against the use of GSTP1-1 as a serum or plasma marker for gastrointestinal tumors.

Patients with acute intestinal infections, in particular, salmonellosis showed in 1/3 during the acute period an insignificant increase of bilirubin and alaninaminotransferase. During early reconvalescence the majority of patients revealed functional changes of the biliary tract, mainly, in the form of hypotensive-hypokinetic type of dyskinesia.

The effect of soy protein on the small bowel mucosa of 18 infants with acute gastroenteritis was studied. The infants were maintained on a protein hydrolysate formula for 6-8 weeks, following which they were readmitted for soy protein challenge studies. Jejunal biopsy was performed before and 24 h after challenge. On the basis of the clinical and histological reaction to soy protein challenge, three groups were identified. Group 1 consisted of three infants who had clinical and histological reaction. There was associated depletion of mucosal enzymes, lactase, sucrase, malatase, alkaline phosphatase, and blood xylose levels. Group 2 consisted of seven infants who had histological reaction but no clinical symptoms. Two of these seven infants, however, developed clinical reaction when rechallenged with soy protein 2 and 90 days later. Following challenge, mucosal enzymes and blood xylose levels were depressed in five of the seven infants tested. Group 3 consisted of eight infants who did not have either a clinical or a histological reaction. The mucosal enzymes and blood xylose levels were not depressed in four infants tested. The present study shows that the small bowel mucosa of some young infants recovering from acute gastroenteritis remains sensitive to soy protein for a variable period of time. The feeding of soy protein to these infants may result in the persistence of mucosal damage and perpetuation of diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum diamine oxidase (DAO) activities were measured in 20 control patients and in 24 patients with gastroenteritis. Results (mean +/- SE) were as follows: 1) control patients (n = 20), 36.2 +/- 5.7 pmol h-1 ml-1; 2) gastroenteritis (acute phase) (n = 11), 31 +/- 4.9 pmol h-1 ml-1; 3) gastroenteritis (healing phase) (n = 21), 18 +/- 1.9 pmol h-1 ml-1. Patients with gastroenteritis in the healing phase had significantly lower DAO values when compared to control patients (p less than 0.001) and to gastroenteritis patients in the acute phase (p less than 0.05). In eight patients where both acute and healing phase values could be measured, a significant decrease between acute and healing phase was found (p less than 0.001). Patients with severe gastroenteritis tended to have lower DAO activity values than patients with moderate gastroenteritis (p = 0.10). Our results support the hypothesis that serum DAO activity is a marker of the total mass of functional enterocytes, the decrease of which during gastroenteritis is reflected in a decrease of serum DAO activity values.

Fecal lysozyme excretion was determined in two hundred children and adolescent. In sixty three infants with enteritis due to Rotavirus the fecal lysozyme level was found to be significant higher than in the feces of a group of healthy infants (p less than 0.01). Elevated fecal lysozyme excretion could be detected in patients with untreated Crohn's disease. After treatment with Salazosulfapyridine, Prednisone and elemental diet during six week a significant drop in fecal lysozyme level was observed (p less than 0.01). In eighteen adolescent with Colitis ulcerosa and Crohn's disease the lysozyme level of colonic mucosa was found to be significant higher than a control group (p less than 0.01). The fecal lysozyme excretion can be used as an indicator for the clinical activity of the disease, as a control for therapeutic efficiency and a marker for a relapse.

The histopathological changes that occur in the jejunal mucosa of humans infected with the Norwalk or Hawaii agent of acute infectious nonbacterial gastroenteritis ("viral" gastroenteritis) have ben well characterized. The pathogenesis of diarrhea in this syndrome remains unknown; however, recent reports have suggested a possible role for the adenylate cyclase system. In this combined paper, two groups of investigators working independently and employing slightly different techniques report that: (1) there is marked interindividual variation in the apparent specific activity of adenylate cyclase in human jejunal biopsy tissue; (2) such variation can be minimized by expressing enzyme activity as a fraction of maximal that can be stimulated by 10(-2) M sodium fluoride; and (3) adenylate cyclase activity in jejunal mucosa is not increased during diarrhea or illness in human viral gastroenteritis, therefore suggesting no role for the adenylate cyclase system in the pathogenesis of diarrhea in this common clinical entity.

Random fecal chymotrypsin activity and fecal alpha 1-antitrypsin (FA-1-AT) concentrations were determined in 11 children with cystic fibrosis, 5 children with Crohn's disease, 9 children with chronic aspecific diarrhea, 85 children with acute gastroenteritis, and 54 control children. Cystic fibrosis patients showed only very low fecal chymotrypsin values that did not overlap with values obtained in patients with either acute or chronic diarrhea. When compared with our control group, a significant increase of FA-1-AT concentrations was found only in children with Crohn's disease. Normal values were found in all patients with either chronic aspecific diarrhea or cystic fibrosis, while 12 of 85 children with acute gastroenteritis showed FA-1-AT concentrations above the 95th percentile of control children. We conclude that diarrhea (either acute or chronic) does not significantly decrease the clinical usefulness of fecal chymotrypsin activity measurements in the diagnosis of pancreatic insufficiency, while acute (gastroenteritis) but not chronic (chronic aspecific diarrhea, cystic fibrosis) diarrhea can give rise to protein losing and FA-1-AT concentrations similar to those found in Crohn's disease.

We present a case of a 11/2-year-old boy with toxic enteritis, consecutive consumption coagulopathy, and sever brain damage. During the acute phase we found high activity of the BB isoenzyme of creatine kinase in cerebrospinal fluid, but not in the serum. Isoenzyme MM could also be found in the spinal fluid (37.9% of the total activity). We conclude that analysis for creatine kinase isoenzymes in spinal fluid is of clinical importance.

Over a 6-week period, 35 (41%) of 86 infants admitted with diarrhea and dehydration were found to have human rotavirus (HRV) gastroenteritis, using the Rotazyme (RTZ) test. Serum transaminase levels were measured on 44 infants on admission and 72 infants during the first 3 days of hospitalization. On admission, RTZ-positive (RTZ+) infants had higher mean and median alanine aminotransferase (ALT) levels [mean 87.5 U/L in RTZ+ vs. 50.0 U/L in RTZ-negative (RTZ-), p = 0.001; medium 60 U/L in RTZ+ vs. 41 U/L in RTZ- infants, p = 0.002], and higher mean and median aspartate aminotransferase (AST) levels (mean 64.3 U/L in RTZ+ vs. 44.0 U/L in RTZ- infants, p = 0.008; median 67.5 U/L vs. 42.0 U/L, respectively, p = less than 0.05). On admission, 72% of RTZ+ vs. 19% of RTZ- infants had ALT levels greater than 50 U/L (p = 0.0004). Maximum ALT levels from the first 3 days were also higher in the RTZ+ group (67.7% of RTZ+ vs. 34.1% of RTZ- having levels greater than 50 U/L, p = 0.005). Transaminase elevations did not correlate with dehydration of any electrolyte abnormalities. These findings suggest that transaminase elevations are common in infants hospitalized with HRV enteritis.

Assays for (Na+-K+)-ATPase and basal, fluoride stimulated and percentage of activation of adenylate cyclase have been established for small portions of human jejunal biopsies. Control means and ranges have been established for each activity in a group of children with failure to thrive but no gastrointestinal disease. Activities of (Na+-K+)-ATPase and percentage of activation and basal activity of adenylate cyclase are increased in children with toddler diarrhea. (Na+-K+)-ATPase activity is reduced in children with active postenteritis syndrome, and recovery from this syndrome is associated with an increase in this activity and of percentage of activation and basal activity of adenylate cyclase.

A case of prolonged diarrhoea following Escherichia coli 0111 gastroenteritis is reported. Electron microscopy of the jejunal biopsy revealed effacement of the brush border and attachment of bacteria by pedestal formation. Specific activities of brush border enzymes showed marked depression of disaccharidases, zinc-resistant alpha-glucosidase, and alkaline phosphatase. In contrast, marker enzymes for basolateral membranes and endoplasmic reticulum were unaffected. The biochemical changes support the pathogenic mechanism suggested by ultrastructural studies previously reported.