Metabolic phenotyping to monitor chronic enteritis canceration.

INTRODUCTION: Colorectal cancer (CRC) remains an incurable disease. Previous metabolomic studies show that metabolic signatures in plasma distinguish CRC patients from healthy controls. Chronic enteritis (CE) represents a risk factor for CRC, with a 20 fold greater incidence than in healthy individuals. However, no studies have performed metabolomic profiling to investigate CRC biomarkers in CE. OBJECTIVE: Our aims were to identify metabolomic signatures in CRC and CE and to search for blood-derived metabolite biomarkers distinguishing CRC from CE, especially early-stage biomarkers. METHODS: In this case-control study, 612 subjects were prospectively recruited between May 2015 and May 2016, and including 539 CRC patients (stage I, 102 cases; stage II, 259 cases; stage III, 178 cases) and 73 CE patients. Untargeted metabolomics was performed to identify CRC-related metabolic signatures in CE. RESULTS: Five pathways were significantly enriched based on 153 differential metabolites between CRC and CE. 16 biomarkers were identified for diagnosis of CRC from CE and for guiding CRC staging. The AUC value for CRC diagnosis in the external validation set was 0.85. Good diagnostic performances were also achieved for early-stage CRC (stage I and stage II), with an AUC value of 0.84. The biomarker panel could also stage CRC patients, with an AUC of 0.72 distinguishing stage I from stage II CRC and AUC of 0.74 distinguishing stage II from stage III CRC. CONCLUSIONS: The identified metabolic biomarkers exhibit promising properties for CRC monitoring in CE patients and are superior to commonly used clinical biomarkers (CEA and CA19-9).

Inflammatory bowel disease (IBD) in horses: a retrospective study exploring the value of different diagnostic approaches.

BACKGROUND: Diagnosing IBD in horses is challenging and requires a multimodal approach, since no conclusive diagnostic test is available. The objectives of this study were to provide an overview of population characteristics, results of applied diagnostic tests, treatment modalities and outcome in a large group of horses thought to have IBD and that were presented to four large equine referral hospitals, and to provide an exploratory investigation of possible associations between results of applied diagnostic tests, applied treatment modalities and outcome. A retrospective case series was performed across four large equine referral hospitals. Seventy-eight horses, thought to have IBD were included. Case history, clinical findings, diagnostic test results including oral glucose tolerance test (OGTT) and enteral biopsies (both duodenal and rectal), applied therapy and outcome were studied. A Chi-Square test was used to identify associations between results of diagnostic tests, treatment and outcome. P-values < 0.05 were considered significant. RESULTS: Lethargy, diarrhoea, recurrent colic and weight loss were recorded in respectively 21,8%; 14,1%; 28,2% and 78,2% of cases. Over 70% of horses thought to have IBD had an abnormal OGTT. Only weight loss was significantly associated with aberrant enteral biopsy results, but not with abnormal OGTT results or low blood total protein. There was no association between an aberrant biopsy result and a disturbed OGTT. There was no association between either OGTT results or enteral biopsy results and a low blood total protein content, presence of gastric ulcer disease or an aberrant endoscopic aspect of the duodenal entrance. CONCLUSIONS: Weight loss is a highly prevalent symptom in IBD suspected horses. Enteral biopsies may be a useful diagnostic aid in the work-up of horses thought to suffer from IBD, however further research is required to demonstrate their true diagnostic value. Until more standardized scientific research is available, one should be careful with the interpretation of enteral biopsy results There is a need for better standardization of enteral biopsy procedures and the histopathological scoring of biopsies.

IMMUNOHISTOCHEMICAL AND MOLECULAR EVIDENCE OF PUTATIVE NEORICKETTSIA INFECTION IN COATIS ( NASUA NASUA) FROM SOUTHERN BRAZIL.

The pathologic, molecular, and immunohistochemical findings associated with Neorickettsia helminthoeca are described in coatis ( Nasua nasua). Tissue sections (small intestine, lungs, kidney, liver, and spleen) of coatis ( n = 3) that died at the Bela Vista Biological Refuge, Foz do Iguaçu, Paraná, southern Brazil were routinely processed from histopathology. Selected formalin-fixed paraffin-embedded (FFPE) tissue sections of the small intestine, lungs, and spleen were used in an immunohistochemical (IHC) assay designed to identify the antigens of N. helminthoeca. Additionally, FFPE tissue sections of the small intestine were used to demonstrate antigens of canine parvovirus-2 (CPV-2) by IHC. Histopathology revealed chronic enteritis in all coatis. Parasitic enteritis was diagnosed in two coatis; one of these contained examples of a trematode within the lumen of the small intestine and the ovum of a trematode encysted in the intestinal mucosa. Other significant pathologic findings included interstitial pneumonia ( n = 2) and pyogranulomatous splenitis ( n = 1). Positive immunolabeling for N. helminthoeca was identified within macrophages of the small intestine and reticuloendothelial cells within the germinal centers of the spleen of all coatis; the intestinal trematode was N. helminthoeca IHC-positive. All pulmonary sections revealed negative immunolabeling for N. helminthoeca. Furthermore, the antigens of CPV-2 were not identified in the intestine of any coati. These findings indicate that these coatis were infected by N. helminthoeca, but since clinical and gross pathological findings were not recorded, it is uncertain if this pathogen produced clinical disease in this canid host; therefore, coatis may be asymptomatic or dead-end hosts for this organism.

Stopping Feline Coronavirus Shedding Prevented Feline Infectious Peritonitis.

After an incubation period of weeks to months, up to 14% of cats infected with feline coronavirus (FCoV) develop feline infectious peritonitis (FIP): a potentially lethal pyogranulomatous perivasculitis. The aim of this study was to find out if stopping FCoV faecal shedding with antivirals prevents FIP. Guardians of cats from which FCoV had been eliminated at least 6 months earlier were contacted to find out the outcome of their cats; 27 households were identified containing 147 cats. Thirteen cats were treated for FIP, 109 cats shed FCoV and 25 did not; a 4-7-day course of oral GS-441524 antiviral stopped faecal FCoV shedding. Follow-up was from 6 months to 3.5 years; 11 of 147 cats died, but none developed FIP. A previous field study of 820 FCoV-exposed cats was used as a retrospective control group; 37 of 820 cats developed FIP. The difference was statistically highly significant (p = 0.0062). Cats from eight households recovered from chronic FCoV enteropathy. Conclusions: the early treatment of FCoV-infected cats with oral antivirals prevented FIP. Nevertheless, should FCoV be re-introduced into a household, then FIP can result. Further work is required to establish the role of FCoV in the aetiology of feline inflammatory bowel disease.

Cerebral Metabolic Analysis of Patients With Colorectal Cancer and Chronic Enteritis: Inquiry Into Gut-Brain Crosstalk.

Gut-brain crosstalk has been demonstrated previously. However, brain metabolic patterns of colorectal cancer and chronic enteritis remain unclear. A better understanding of gut-brain crosstalk from a radiological perspective is necessary. We conducted a retrospective study in which we acquired 18F-fluorodeoxyglucose positron emission tomography in 45 colorectal cancer cases, 45 age- and sex-matched chronic enteritis patients, and 45 age- and sex-matched healthy controls. We calculated a scaled sub-profile pattern based on principal component analysis and metabolic connectivity to explore the brain metabolic model and analyzed correlations between various brain regions and cancer to identify potential neuroimaging markers for non-pharmaceutical therapies. We found a characteristic cerebral metabolic pattern in colorectal cancer patients, which mainly involved visceral sensation and both affective and cognitive psychological processes. The metabolic patterns of patients with colorectal cancer and chronic enteritis were similar but not identical. The metabolic connectivity of the postcentral gyrus and paracentral lobule was found to be significantly different between the controls and patients with colorectal cancer (p < 0.05, false discovery rate correction). The maximal standard uptake value of the cancer focus in colorectal cancer patients was negatively correlated with the dorsolateral superior frontal gyrus (p < 0.05). Patients with colorectal cancer may show abnormal glucose cerebral metabolism characterized by "point-line-surface." This preliminary study revealed the cerebral metabolic characteristics and neurobiological mechanisms of colorectal cancer and chronic enteritis (ChiCTR2000041020; registered December 16, 2020).

The Yersinia Phage X1 Administered Orally Efficiently Protects a Murine Chronic Enteritis Model Against Yersinia enterocolitica Infection.

Yersinia enterocolitica is generally considered an important food-borne pathogen worldwide, especially in the European Union. A lytic Yersinia phage X1 (Viruses; dsDNA viruses, no RNA stage; Caudovirales; and Myoviridae) was isolated. Phage X1 showed a broad host range and could effectively lyse 27/51 Y. enterocolitica strains covering various serotypes that cause yersiniosis in humans and animals (such as serotype O3 and serotype O8). The genome of this phage was sequenced and analyzed. No toxin, antibiotic-resistance or lysogeny related modules were found in the genome of phage X1. Studies of phage stability confirmed that X1 had a high tolerance toward a broad range of temperatures (4-60°C) and pH values (4-11) for 1 h. The ability to resist harsh acidic conditions and enzymatic degradation in vitro demonstrated that phage X1 is suitable for oral administration, and in particular, that this phage can pass the stomach barrier and efficiently reach the intestine in vivo without losing infectious ability. The potential of this phage against Y. enterocolitica infection in vitro was studied. In animal experiments, a single oral administration of phage X1 at 6 h post infection was sufficient to eliminate Y. enterocolitica in 33.3% of mice (15/45). In addition, the number of Y. enterocolitica strains in the mice was also dramatically reduced to approximately 103 CFU/g after 18 h compared with 107 CFU/g in the mice without phage treatment. Treatment with phage X1 showed significant improvement by intestinal histopathologic observations. Moreover, proinflammatory cytokine levels (IL-6, TNF-α, and IL-1ß) were significantly reduced (P < 0.05). These results indicate that phage X1 is a promising candidate to control infection by Y. enterocolitica in vivo.

Urogenital myiasis caused by Lucilia sericata (Diptera: Calliphoridae) in a domestic rabbit in Italy.

The report describes a case of urogenital myiasis in a domestic rabbit Oryctolagus cuniculus L. (Lagomorpha: Leporidae) caused by Lucilia sericata (Meigen; Diptera: Calliphoridae) in region Emilia-Romagna (Northern Italy). The case, occurring in June 2018, is the first one involving L. sericata as an agent of myiasis in a domestic rabbit in Italy. Species identification was based on morphological investigations of males through identification keys. The rabbit developed the urogenital myiasis as a consequence of chronic enteritis causing an accumulation of faeces in the perianal and perineal region.

Decreased plasma amino acid concentrations in cats with chronic gastrointestinal diseases and their possible contribution in the inflammatory response.

In humans, plasma amino acids (AAs) levels are used as dynamic nutritional markers. Moreover, some AAs are associated with chronic inflammation. In this study, we analyzed plasma AA profiles in cats with chronic gastrointestinal (GI) diseases. Eight healthy controls (HCs) and 12 client-owned cats with chronic GI diseases including chronic enteritis (n=8) and neoplasms (n=4) were recruited. Plasma albumin, total protein, and 22 AAs (11 essential and 11 non-essential AAs) levels were estimated. There was no significant difference in plasma albumin and total protein concentrations between the cats with chronic GI diseases and HCs. The plasma concentrations of 7 essential AAs (arginine, histidine, lysine, methionine, phenylalanine, taurine, and tryptophan) and 7 non-essential AAs (asparagine, aspartic acid, glutamic acid, glycine, hydroxyproline, proline, and serine) were significantly decreased in the cats with chronic GI diseases (P<0.05). Moreover, plasma histidine and tryptophan levels were inversely correlated with severity of symptoms (histidine: rs=-0.7781, P<0.005; tryptophan: rs=-0.6040, P<0.05). To examine the contribution of altered AAs levels in the inflammatory response, feline macrophages were stimulated by lipopolysaccharides (LPS) with or without histidine, and the expression of interleukin-8 (IL-8) mRNA was quantified. The expression of IL-8 mRNA was significantly increased in the LPS-stimulated feline macrophages (P<0.05). Histidine almost suppressed the LPS-induced IL-8 expression in the feline macrophages (P<0.05). Our findings suggest that plasma AAs levels are more sensitive nutritional markers than albumin and total protein levels in cats with chronic GI diseases. There is a possibility that the decrease of histidine levels in cats with GI diseases is associated with chronic inflammation.

Association between lymphocyte antigen receptor gene rearrangements and histopathological evaluation in canine chronic enteropathy.

Although definitive diagnosis of chronic enteropathy (CE) and gastrointestinal (GI) lymphoma requires histopathological evaluation of the GI tract, these conditions are often still difficult to differentiate from each other. Polymerase chain reaction (PCR) for antigen receptor gene rearrangements (PARR) has been applied recently as an adjunctive for diagnosis of lymphoid tumors; however, its clinical value in canine CE and GI lymphoma remains unclear. The purpose of this study was to investigate the relationship between PARR and histopathological diagnosis, degree of enteritis or lymphoma, and long-term prognosis in dogs, in order to evaluate the clinical significance of PARR. Endoscopic biopsy specimens obtained from 96 dogs with chronic enteritis (mild, n=14; moderate, n=20; marked, n=62) and 21 dogs with GI lymphoma were used. Clonality was observed in 51% of the animals with chronic enteritis; interestingly, it was found in 29% of those with only mild enteritis. In dogs with marked enteritis, the rate of PARR was higher in those with lymphocyte epitheliotropism than in those without epitheliotropism. The sensitivity of PARR in animals with GI lymphoma was 76%. There was no significant prognostic difference between chronic enteritis with or without clonal rearrangements. In contrast, dogs histopathologically diagnosed with marked enteritis had a significantly shorter survival time than did those with mild or moderate enteritis. While the significance of PARR in the diagnosis of GI lymphoma remains uncertain, the pathological roles of clonally expanding lymphocytes in canine CE should be investigated further.

Stanniocalcin-1 protects bovine intestinal epithelial cells from oxidative stress-induced damage.

Chronic enteritis can produce an excess of reactive oxygen species resulting in cellular damage. Stanniocalcin-1(STC-1) reportedly possesses anti-oxidative activity, the aim of this study was to define more clearly the direct contribution of STC-1 to anti-oxidative stress in cattle. In this study, primary intestinal epithelial cells (IECs) were exposed to hydrogen peroxide (H2O2) for different time intervals to mimic chronic enteritis-induced cellular damage. Prior to treatment with 200 µM H2O2, the cells were transfected with a recombinant plasmid for 48 h to over-express STC-1. Acridine orange/ ethidium bromide (AO/EB) double staining and trypan blue exclusion assays were then performed to measure cell viability and apoptosis of the cells, respectively. The expression of STC-1 and apoptosis-related proteins in the cells was monitored by real-time PCR and Western blotting. The results indicated that both STC-1 mRNA and protein expression levels positively correlated with the duration of H2O2 treatment. H2O2 damaged the bovine IECs in a time-dependent manner, and this effect was attenuated by STC-1 over-expression. Furthermore, over- expression of STC-1 up-regulated Bcl-2 protein expression and slightly down-regulated caspase-3 production in the damaged cells. Findings from this study suggested that STC-1 plays a protective role in intestinal cells through an antioxidant mechanism.

Retención de cápsula endoscópica como complicación de enteritis actínica: reporte de un caso / Retention of capsule endoscopy as a complication of radiation enteritis: a case report

La cápsula endoscópica es un método, que ha modificado el enfoque diagnóstico de numerosos procesos patológicos en el intestino delgado, sin embargo presenta complicaciones como la retención de la misma. Se estima en la literatura mundial que esta suele ocurrir en menos del 2% de los casos. Femenino de 40 años de edad, con antecedente de cáncer de cuello uterino (2011) en tratamiento con quimioterapia, radioterapia convencional y braquiterapia, que presenta cuadro clínico caracterizado por dolor urente en mesogastrio, y emesis de aspecto biliosos. Ruidos hidroaéreos presentes, dolor a la palpación de mesogastrio sin irritación peritoneal. Radiografía de abdomen y ecosonograma abdominal normales. TAC abdomino pélvica con contraste oral con adecuada progresión de contraste hasta el recto. Se practica gastroscopia y colonoscopia sin evidencia de alteraciones. En vista de persistencia de sintomatología se indica realización de cápsula endoscópica observando en íleon distal, a los 246 minutos del paso duodenal, área muy congestiva, con una úlcera circunferencial friable, que no permite el avance de la misma. Se indica tratamiento médico con laxantes por 72 horas, el cual es infructuoso, por lo cual es llevada a mesa operatoria por presentar signos francos de obstrucción intestinal. Los hallazgos fueron: adherencias en flanco y fosa ilíaca derecha, las cuales fueron liberadas, y segmento de íleon a 10 cm de la válvula ileocecal con inflamación franca, practicándose resección y anastomosis termino-lateral. El estudio histopatológico reportó enteritis crónica activa exulcerada, necrosis fibrinoide de pequeños vasos, y fibrosis en la submucosa. Paciente con post-operatorio exitoso decidiéndose el egreso de la institución. Excelente correlación entre los hallazgos de la cápsula endoscópica y la intervención quirúrgica. Los hallazgos de la cirugía se encuentran relacionados al uso de radioterapia convencional, por lo cual recomendamos la realización de pexia...

Capsule endoscopy is a method that has changed the diagnostic approach to many pathological processes in the small intestine, but it has complications such as retention of the same, is estimated in the literature that this usually occurs in less than 2% cases. Women 40 years of age, with a history of cervical cancer (2011) undergoing chemotherapy, conventional radiation therapy, and brachytherapy, presenting clinical picture characterized by burning pain in midgut, and bilious emesis aspect. Present bowel sounds, tenderness of mesogastrium without peritoneal irritation. Abdominal radiography and abdominal ultrasonography normal. Pelvic CT with oral contrast Abdomino with progression adequate contrast to the rectum. Gastroscopy and colonoscopy was performed without evidence of tampering. In view of the persistence of symptoms embodiment shown in watching endoscopic capsule distal ileum, to 246 minutes of step duodenal study, very congestive area with a circumferential friable ulcer which does not allow the advance thereof. Indicated medical treatment with laxatives for 72 hours being fruitless, operating table being carried by presenting overt signs of intestinal obstruction. The findings were: adhesions flank and right lower quadrant, which were released and ileal segment 10 cm from the ileocecal valve with frank inflammation resection and end-side anastomosis. Histopathological study reported chronic active enteritis exulcerada, fibrinoid necrosis of small vessels, and fibrosis in the submucosa. Postoperative patient deciding successful graduation from the institution. Excellent correlation between the findings of capsule endoscopy and surgery. The findings at surgery are related to the use of conventional radiotherapy, so we recommend an pexia of the organs that are in the radiation field, prior to it, and intestinal transit before indicating capsule endoscopy

[Infections of the small intestine]. / Infections de l'intestin grêle.

Small intestinal infections are, together with colonic infections, amongst the most frequent occurring diseases worldwide and they harass mankind. Especially among young children there are enormous numbers of deaths due to diarrhoeal disease. They can be caused by a great diversity of pathogens and their pathological and epidemiological features as well as their incidence can often differ in different areas of the world.In this paper the most common causes of small intestinal infections are reviewed and some characteristics of their clinical and histological aspects are described. Moreover, the different infectious diseases are classified into acute and chronic as the recognition of the type of inflammatory infiltrate may be help ful to make a correct diagnosis.

Paratuberculosis bovina: ¿conocemos la situación real de la enfermedad en la ganadería colombiana / Paratuberculose bovina: Não sabemos a real situação da doença no gado colombiano / Bovine paratuberculosis: ¿Do we know the real situation of this disease in Colombian cattle

El Mycobacterium avium subespecies paratuberculosis (Map) es el agente etiológico causante de una gastroenteritis granulomatosa severa en rumiantes, conocida como paratuberculosis bovina o enfermedad de Johne, caracterizada por la presentación de diarrea persistente y emaciación progresiva, que causan finalmente la muerte. Los animales menores de 6 meses de edad son los más susceptibles a contraer la infección por medio de la ingestión del bacilo a través de la leche o el pasto contaminado, o por vía transplacentaria y a pesar de que excretan el agente en las heces, no presentan signos clínicos antes de 2 a 5 años, tiempo que dura el periodo de incubación. Debido a la falta de tratamiento, cualquier medida de control debe estar enfocada en la identificación de los animales infectados mediante pruebas diagnosticas confiables, que permitan detectar el agente antes del inicio de los signos clínicos para evitar la diseminación de la infección a los animales del mismo hato o a otros, en caso de la venta de animales asintomáticos. La infección es de distribución mundial y es responsable de importantes pérdidas económicas en la industria de la producción bovina. En nuestro medio, se ha documentado la enfermedad en hatos lecheros del municipio de San Pedro de los Milagros (Antioquia), pero se cree que hay muchas otras zonas infectadas, por lo que se requiere el desarrollo de métodos eficientes de detección, diagnóstico y control de la enfermedad. En la presente revisión, se tratarán los aspectos concernientes a la paratuberculosis bovina y finalmente se destacan algunas perspectivas de investigación en esta enfermedad.

Mycobacterium avium subspecies paratuberculosis (Map) is the etiologic agent of a severe granulomatous gastroenteritis in ruminants, known as bovine paratuberculosis or Johne’s disease and characterized by persistent diarrhea and progressive emaciation that finally cause death. Calves under 6 months of age are the most susceptible to this bacterial infection by transplacental route, milk consumption or grassland contaminated feeding and although, they do not show clinical signs until they are 2 to 5 years old (incubation period), they commonly spread Map through their feces. A remarkable difficulty concerning Johne´s disease is its lack of appropriate treatment; therefore any control scheme must be focused in identification of infected animals by reliable diagnostic tests before the appearance of clinical manifestations, in order to avoid dissemination of the infection to animals of the same or different herd, particularly when marketing possible asymptomatic animals. The infection has a worldwide distribution and it is responsible of important economic losses in cattle industry. Bear to us, the disease has been reported in dairy herds of the municipality of San Pedro de los Milagros (Antioquia), but it is thought that there are many other infected regions, which makes more prominent the need of efficient methods for Map detection for rapid diagnosis and efficient control of the dissemination of the infection. In this review, we highlight some important features of bovine paratuberculosis and provide some insight regarding probable research perspectives of this disease.

O Mycobacterium avium subespécie paratuberculose (Map) é o agente que provoca uma severa gastroenterite granulomatosa em ruminantes, conhecida como doença de Johne ou paratuberculose bovina, caracterizada pela apresentação de diarréia persistente e caquexia progressivo, acabou provocando a morte ss animais com menos de 6 meses são os mais suscetíveis a contrair a infecção por tuberculose através da ingestão de leite contaminado ou erva ou via a transmissão e não obstante o facto de o agente excretada nas fezes, não há sinais clínicos antes de 2 a 5 anos, enquanto que o período de incubação dura. Devido à falta de tratamento, qualquer medida de controle deve estar centrada na identificação de animais infectados através de testes de diagnóstico fiável, para identificar o agente antes do início dos sinais clínicos para evitar a disseminação da infecção para os animais do mesmo rebanho ou outros, se a venda de animais assintomáticos. A infecção é distribuída em todo o mundo e é responsável por grandes perdas econômicas para a produção da indústria bovina. Na nossa área, tem documentado a doença em rebanhos leiteiros no município de San Pedro de los Milagros (Antioquia), mas cree que existem muitas outras áreas infectadas, aquilo que é exigido pelo desenvolvimento de métodos eficazes de detecção, diagnóstico e controle de doenças. Nesta revisão, vai tratar dos aspectos relativos à paratuberculose bovina e, finalmente, destaca algumas perspectivas de investigação sobre esta doença.