Patients with radiation enteritis present regulatory T cell impairment associated with CTLA-4.

Radiation enteritis is one of the most common side effects of ionizing radiation in patients with pelvic cancers. Increasing amounts of evidence indicate that pro-inflammatory responses significantly contribute to the development of radiation enteritis. In this study, we investigated the association between T regulatory (Treg) cells and the risk of developing radiation enteritis in cervical cancer patients. The following observations were made. First, the frequencies of CD25hiFoxp3+ Treg cells were significantly lower in patients with radiation enteritis than in both healthy subjects and cervical cancer patients without radiation enteritis. Also, patients with the more severe grade 3 enteritis presented significantly lower Treg levels than patients with the more common grade 1 enteritis. Second, the expression of several molecules associated with Treg function, including CTLA-4, IL-10, TGF-ß, and perforin, was significantly lower in patients with radiation enteritis than in healthy subjects. In patients without radiation enteritis, however, only CTLA-4, but not other Treg-associated suppressive molecules, was reduced in Treg cells. Third, Treg cells can markedly suppress CD8 T cell proliferation, but in patients with radiation enteritis, this function of Treg cells was significantly impaired, in a manner that was associated with lower CTLA-4 expression. Overall, these data suggest that the frequency and function of Treg cells is negatively associated with the risk of developing enteritis following radiation. In clinical practice, the characteristics of Treg cells may be considered to evaluate the risk of developing enteritis if the cancer patient is receiving ionizing radiation.

Ionizing radiation induces BH4 deficiency by downregulating GTP-cyclohydrolase 1, a novel target for preventing and treating radiation enteritis.

Radiation enteritis (RE) is a common side effect after radiotherapy for abdominal cancer. RE pathogenesis is complicated, with no drugs available for prevention or treatments. Intestinal ischemia is a key factor in the occurrence and development of enteritis. The effect of ionizing radiation (IR) on intestinal ischemia is unknown. Deficiency of tetrahydrobiopterin (BH4) produced by GTP-cyclohydrolase 1 (Gch1) is important in ischemic diseases. This study focused on the relationship of Gch1/BH4 between intestinal ischemia in radiation enteritis. BH4 levels were analyzed by high-performance liquid chromatography in humans and rats after radiotherapy. Intestinal blood perfusion was measured by laser doppler flow imaging. Vascular ring tests determined the diastolic functions of rat mesenteric arteries. Gene, protein, and immunohistochemical staining experiments and inhibitor interventions were used to investigate Gch1 and endothelial NOS (eNOS) in rat mesenteric arteries and endothelial cells. The results showed that IR decreased BH4 levels in patients and rats after radiotherapy and decreased intestinal blood perfusion in rats. The degree of change in intestinal ischemia was consistent with intestinal villus injury. Gch1 mRNA and protein levels and nitric oxide (NO) production significantly decreased, while eNOS uncoupling in arterial and vascular endothelial cells strongly increased. BH4 supplementation improved eNOS uncoupling and NO levels in vascular endothelia after IR. The results of this study showed that downregulation of Gch1 in intestinal blood vessels after IR is an important target in RE. BH4 supplementation may prevent intestinal ischemia and improve vascular endothelial function after IR. These findings have clinical significance for the prevention and treatment of RE.

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).

Eosinophil counts in colonic tissue eosinophilia: Investigating specificity and sensitivity of cutoff points and comparing two counting methods.

BACKGROUND/AIMS: The aim of this study was to investigate the specificity and sensitivity of eosinophil cutoff points defining the colonic tissue eosinophilia (TE) and compare the yield of reporting the highest count versus the mean of five high-power fields (HPFs). MATERIALS AND METHODS: One hundred and seventy-one cases of colonic TE, including 22 primary eosinophilic colitis (PEC) cases, were compared to one hundred and twenty-one normal controls in the University of Jordan. The highest eosinophil count (EC) and the mean of five HPFs were recorded. The receiver operating characteristic curve (ROC) analysis was used to find the cutoff point with the best sensitivity and specificity. RESULTS: There was no significant advantage of counting five fields over counting the most densely populated HPF. Using 30 eosinophils per HPF achieved 80% sensitivity and 65% specificity. This point is close to the mean in normal controls plus one standard deviation (SD) (29 per HPF). However, there was overlap between normal counts and TE, using 30 as a cutoff point resulted in 35% false-positive rate. There was no reliable cutoff point to differentiate PEC from secondary TE. CONCLUSION: We recommend reporting the highest EC in colonic biopsies and using 30 as a cutoff point, bearing in mind the overlap with normal and correlating with the clinical team to not treat asymptomatic patients. Clinicopathological correlation is essential to separate PEC from secondary TE.

Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study.

BACKGROUND: Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need among patients with EG for more precise diagnostic tools. OBJECTIVE: We aimed to develop tissue- and blood-based diagnostic platforms for EG. METHODS: Patients with EG and control subjects without EG were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers-associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. EGDP18 scores were derived from the expression of 18 highly dysregulated genes, and blood EG scores were derived from dysregulated cytokine/chemokine levels. RESULTS: Gastric biopsy specimens and blood samples from 185 subjects (patients with EG, n = 74; control subjects without EG, n = 111) were analyzed. The EGDP (1) identified patients with active EG (P < .0001, area under the curve ≥ 0.95), (2) effectively monitored disease activity in longitudinal samples (P = .0078), (3) highly correlated in same-patient samples (antrum vs body, r = 0.85, P < .0001), and (4) inversely correlated with gastric peak eosinophil levels (r = -0.83, P < .0001), periglandular circumferential collars (r = -0.73, P < .0001), and endoscopic nodularity (r = -0.45, P < .0001). For blood-based platforms, eotaxin-3, thymus and activation-regulated chemokine, IL-5, and thymic stromal lymphopoietin levels were significantly increased. Blood EG scores (1) distinguished patients with EG from control subjects without EG (P < .0001, area under the curve ≥ 0.91), (2) correlated with gastric eosinophil levels (plasma: r = 0.72, P = .0002; serum: r = 0.54, P = .0015), and (3) inversely correlated with EGDP18 scores (plasma: r = -0.64, P = .0015; serum: r = -0.46, P = .0084). Plasma eotaxin-3 levels strongly associated with gastric CCL26 expression (r = 0.81, P < .0001). CONCLUSION: We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and clinical readiness tools for this emerging rare disease.

Clinical and pathological profile of eosinophilic gastroenteritis.

BACKGROUND: Eosinophilic gastroenteritis (EoGE) can be diagnosed on the basis of histologic criteria; however, the pathology is considered to be heterogeneous. There is no consensus on the management of this enigmatic disorder with an unknown etiology. PATIENTS AND METHODS: Data for patients diagnosed with EoGE and followed up over a 1-year period were analyzed. Their symptoms, patterns of flares, and type of treatment were documented. The shift in peripheral blood eosinophil levels was also examined. RESULTS: A total of 10 (mean age, 44 years; range: 31-70 years; women, 5) patients were diagnosed with EoGE. The most frequent presenting symptom was abdominal pain, and eight patients were classified with mucosal type of EoGE. Chronic disease or multiple flares were observed in seven out of 10 (70.0%) patients, and all of them had a history of allergy. Four were corticosteroid dependent (three relapsed during corticosteroid tapering and one following corticosteroid withdrawal). One of them received anti-IL5 monoclonal antibody that enabled corticosteroid dose tapering. In four patients with highly elevated initial eosinophil levels at diagnosis, the peripheral eosinophil level correlated with the amelioration and deterioration of their symptoms. The remaining three patients had a single flare without relapse. Two had no history of allergy. CONCLUSION: EoGE is a unique disorder with a variable clinical course. Although further studies are required to confirm our observations, the presence of other allergic disorders is associated with chronicity or multiple flares. Peripheral eosinophil level may be an effective biomarker for recurrence in patients with severe systemic disorders at diagnosis.

Effect of azithromycin and pefloxacin in treatment of acute enteritis based on clinical efficacy comparison.

This paper aims to compare and analyze clinical efficacy of azithromycin and pefloxacin in treatment of acute enteritis. The 160 patients with acute enteritis were randomly divided into a study group (n=80) treated with azithromycin, and a reference group (n=80) treated with pefloxacin. We compared overall treatment efficiency (markedly, effective, invalid), clinical symptoms and signs remission time (antipyretic time, antidiarrheal time, symptoms and signs disappearance time), interleukin-6 and C-reactive protein concentration before and after treatment, adverse reactions rate (nausea, abdominal pain, headache, etc.). In comparison of overall treatment efficiency of the two groups, the results showed that the study group was significantly superior to the reference group (P<0.05). In comparison of clinical symptoms and signs remission time of the two groups, the study group were significantly shorter than the reference group (P<0.05). At the same time, in comparison of levels of interleukin-6 and C-reactive protein concentration after treatment, the study group was significantly superior to the reference group (P<0.05). There was no significant difference between the two groups in incidence of adverse reactions (P<0.05). The efficacy of azithromycin for acute enteritis is better than that of pefloxacin, and it can significantly reduce clinical symptom remission time. Moreover, safe and reliable, it has great value in clinical application.

Serum Biomarkers for the Diagnosis of Eosinophilic Esophagitis and Eosinophilic Gastroenteritis.

Objective Clinically useful serum biomarkers for the diagnosis and monitoring of eosinophilic gastrointestinal diseases are not available. This study was conducted to examine the possible value of eosinophil-related proteins as serum biomarkers. Methods The serum concentrations of 49 cytokines, chemokines, and other proteins were measured in 29 patients with eosinophilic gastrointestinal diseases and 80 controls. Results The levels of interleukin (IL)-5, IL-33, eotaxin-3, and thymic stromal lymphopoietin (TSLP), previously reported as possible biomarkers of eosinophilic esophagitis, were not significantly elevated in the serum. In contrast, the B cell-attracting chemokine (BCA)-1/chemokine (C-X-C motif) ligand (CXCL) 13 and hemofiltrate C-C chemokine (HCC)-1/CC chemokine ligand (CCL) 14α levels were significantly elevated, while the granulocyte chemotactic protein (GCP)-2/CXCL6 levels were suppressed in patients with eosinophilic esophagitis as well as in those with eosinophilic gastroenteritis. The cutaneus T cell-attracting chemokine (CTACK)/CCL27, stromal cell-derived factor (SDF)-1/CXCL12, macrophage inflammatory protein (MIP)-3ß/CCL19, and squamous cell carcinoma antigen (SCCA) 2 levels were elevated only in patients with eosinophilic esophagitis. However, there were large overlaps of data obtained from the patient and control groups, indicating that these serum biomarkers are not adequately sensitive for clinical use with presently available assay systems. Conclusion Of the 49 investigated serum proteins, none were shown to be adequately sensitive for use as biomarkers for the diagnosis or monitoring of eosinophilic gastrointestinal diseases.

Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation.

BACKGROUND: Environmental enteric dysfunction (EED), a condition characterized by small intestine inflammation and abnormal gut permeability, is widespread in children in developing countries and a major cause of growth failure. The pathophysiology of EED remains poorly understood. METHODS: We measured serum metabolites using liquid chromatography-tandem mass spectrometry in 400 children, aged 12-59months, from rural Malawi. Gut permeability was assessed by the dual-sugar absorption test. FINDINGS: 80.7% of children had EED. Of 677 serum metabolites measured, 21 were negatively associated and 56 were positively associated with gut permeability, using a false discovery rate approach (q<0.05, p<0.0095). Increased gut permeability was associated with elevated acylcarnitines, deoxycarnitine, fatty acid ß-oxidation intermediates, fatty acid ω-oxidation products, odd-chain fatty acids, trimethylamine-N-oxide, cystathionine, and homocitrulline, and with lower citrulline, ornithine, polyphenol metabolites, hippurate, tryptophan, and indolelactate. INTERPRETATION: EED is a syndrome characterized by secondary carnitine deficiency, abnormal fatty acid oxidation, alterations in polyphenol and amino acid metabolites, and metabolic dysregulation of sulfur amino acids, tryptophan, and the urea cycle. Future studies are needed to corroborate the presence of secondary carnitine deficiency among children with EED and to understand how these metabolic derangements may negatively affect the growth and development of young children.

Associations between body composition and nutritional assessments and biochemical markers in patients with chronic radiation enteritis: a case-control study.

BACKGROUND: Chronic radiation enteritis (CRE) is defined as loss of absorptive capacity after irradiation due to chronic inflammation and damage of intestinal mucosa, which may lead to varying degrees of malnutrition. The aim of this study was to evaluate the potential correlation between the nutritional status and systemic inflammation in patients with CRE. METHODS: Medical records of 92 patients with CRE and 184 age- and sex-matched controls in a single center from January 2010 to October 2015 were retrospectively reviewed. All enrolled subjects underwent nutritional status analysis, including three different nutritional indices: Nutritional Risk Screening-2002 (NRS-2002), Patient-generated Subjective Global Assessment (PG-SGA) and Controlling Nutritional Status (CONUT), bioelectrical impedance spectroscopy (BIS), and biochemical markers, within 24 h of admission. RESULTS: The results showed that NRS-2002, PG-SGA and CONUT were all positively correlated with neutrophil/lymphocyte ratio (NLR) (r = 0.304, 0.384 and 0.425, all p < 0.001) and C-reactive protein (CRP) (r = 0.357, 0.479 and 0.230, all p < 0.001), while negatively correlated with albumin (r = -0.612, -0.727 and -0.792, all p < 0.001) and total cholesterol (TC) (r = -0.485, -0.545 and -0.473, all p < 0.001) in patients with CRE, respectively. Body cell mass (BCM) has been deemed a key body composition parameter. It was positively correlated with albumin (r = 0.489, p < 0.001) and TC (r = 0.237, p < 0.001), while negatively correlated with NLR (r = -0.140, p = 0.02) and CRP (r = -0.215, p < 0.001). A multivariate linear regression analysis showed that values of intracellular water (ß coefficient = 0.760, p < 0.001), extracellular water (ß coefficient = 0.006, p = 0.011), protein (ß coefficient = 0.235, p < 0.001) and CRP (ß coefficient = 0.001, p = 0.009) were independent determinants of BCM. CONCLUSION: This study revealed that BIS combined with nutritional assessments and biochemical markers were appropriate methods to assess the nutritional and inflammatory status in patients with CRE. Furthermore, the nutritional status was verified to be significantly correlated with systemic inflammation.

Low Triiodothyronine Syndrome in Patients With Radiation Enteritis: Risk Factors and Clinical Outcomes an Observational Study.

The implications of low triiodothyronine syndrome (LT3S) in patients with radiation enteritis (RE) have not been properly investigated. As such, we conducted this cohort study to investigate the association between LT3S and RE, to explore the etiology of LT3S in RE, to evaluate the clinical features and clinical outcomes of LT3S patients, and to inspect the correlation of clinical variables and LT3S in RE.This prospective study included 39 RE patients. Medical records and various laboratory parameters (including thyroidal, tumorous, nutritional, and radiotherapy variables) were collected in all participants.Our results showed that the incidence of LT3S was 84.6% in patients with RE. Total protein (71.7 ±â€Š5.7 vs 63.2 ±â€Š9.6 g/L, P = 0.04) and albumin (ALB, 46.0 ±â€Š4.6 vs 38.7 ±â€Š5.3 g/L, P = 0.01) were significantly lower in LT3S group compared with those in euthyroid group. Standard thyroid-stimulating hormone index (-0.89 ±â€Š2.11 vs -2.39 ±â€Š1.33, P = 0.03) and sum activity of deiodinases (19.74 ±â€Š4.19 vs 12.55 ±â€Š4.32 nmol/L, P = 0.01) were significantly lower in LT3S group. Patients with LT3S suffered longer duration of hospitalization (48.25 ±â€Š23.29 days in LT3S vs 26.75 ±â€Š10.56 days in euthyroid, P = 0.036). Low serum ALB (ß = 0.694, 95% CI = 0.007-0.190, P = 0.037) was the only significant predictor of LT3S.LT3S was common in RE patients. A hypodeiodination condition and a potential pituitary-thyrotroph dysfunction might play a role in the pathophysiology of LT3S in RE. Worse nutritional status and clinical outcomes were confirmed in RE patients with LT3S. Furthermore, total protein and ALB were observed as protective and differentiating parameters of LT3S in RE. In summary, this was the 1st investigation to evaluate the clinical correlation between RE and LT3S, investigate the prevalence of LT3S in RE, and explore the pathogenesis of LT3S, despite the limitation of a relatively small sample size. These results will hopefully encourage future research to place greater emphasis on early identification of LT3S in RE patients.

Lupus enteritis: clinical characteristics and predictive factors for recurrence.

OBJECTIVES: To compare the clinical characteristics of lupus enteritis (LE) and non-enteric lupus (non-LE) patients and identify predictors of LE recurrence. METHODS: We retrospectively reviewed the medical records of 62 systemic lupus erythematosus (SLE) patients in a tertiary hospital who experienced enteric symptoms and underwent abdominal computed tomography scanning between January 1997 and December 2013. We compared the clinical characteristics between LE and non-LE patients and between recurrent LE and non-recurrent LE cases. RESULTS: Out of 62 SLE patients with enteric symptoms, 46 cases (74%) were compatible with LE based on computed tomography findings. The C4 level was decreased in the LE group compared with the non-LE group (9.0 ± 5.6 vs. 12.3 ± 6.2, p = 0.032). Recurrence of LE was observed in 14 patients (28%). Initial involvement at the colon (79% vs. 41%, p = 0.026) and bladder with/without the ureter was more common in the recurrent group (57% vs. 25%, p = 0.048). By multivariate analysis, the hazard ratios of variables associated with recurrence were 4.689 for colon involvement (95% confidence interval: 1.245-17.659, p = 0.0220] and 5.468 for cystitis with/without ureteritis (95% confidence interval: 1.629-18.360, p = 0.006). CONCLUSION: Colon and urinary tract involvement in LE patients may be associated with the recurrence of LE.

Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome.

BACKGROUND: The definition of eosinophilic gastritis (EG) is currently limited to histologic EG based on the tissue eosinophil count. OBJECTIVE: We aimed to provide additional fundamental information about the molecular, histopathologic, and clinical characteristics of EG. METHODS: Genome-wide transcript profiles and histologic features of gastric biopsy specimens, as well as blood eosinophil counts, were analyzed in patients with EG and control subjects (n = 15 each). RESULTS: The peak gastric antrum eosinophil count was 283 ± 164 eosinophils/×400 high-power field in patients with EG and 11 ± 9 eosinophils/×400 high-power field in control subjects (P = 6.1 × 10(-7)). Patients with EG (87%) had coexisting eosinophilic inflammation in multiple gastrointestinal segments; the esophagus represented the most common secondary site. Increased peripheral blood eosinophil counts (patients with EG: 1.09 ± 0.88 × 10(3)/µL vs control subjects: 0.09 ± 0.08 10(3)/µL, P = .0027) positively correlated with peak gastric eosinophil counts (Pearson r(2) = .8102, P < .0001). MIB-1(+) (proliferating), CD117(+) (mast cells), and FOXP3(+) (regulatory T cells, activated T cells, or both) cell counts were increased in patients with EG. Transcript profiling revealed changes in 8% of the genome in gastric tissue from patients with EG. Only 7% of this EG transcriptome overlapped with the eosinophilic esophagitis transcriptome. Significantly increased IL4, IL5, IL13, IL17, CCL26, and mast cell-specific transcripts and decreased IL33 transcripts were observed. CONCLUSION: EG is a systemic disorder involving profound blood and gastrointestinal tract eosinophilia, TH2 immunity, and a conserved gastric transcriptome markedly distinct from the eosinophilic esophagitis transcriptome. The data herein define germane cellular and molecular pathways of EG and provide a basis for improving diagnosis and treatment.

Hematopoietic not systemic impairment of Roquin expression accounts for intestinal inflammation in Roquin-deficient mice.

Roquin, an E3 ligase, is involved in curtailing autoimmune pathology as seen from studies using mice with mutated (Rc3h1(san/san)) or disrupted (Rc3h1(gt/gt)) Rc3h1 gene. The extent to which intestinal immunopathology is caused by insufficient Roquin expression in the immune system, or by Roquin impairment in non-hematopoietic cells, has not been determined. Using bone marrow cells from Rc3h1(gt/gt) mice transferred into irradiated normal mice (Rc3h1(gt/gt) → NL chimeras), we show that inflammation developed in the small intestine, kidney, lung, liver, and spleen. Proinflammatory cytokine levels were elevated in lamina propria lymphocytes (LPLs). Inflammation in the liver was accompanied by areas of hepatocyte apoptosis. Lung inflammation consisted of an influx of both T cells and B cells. Small intestinal LPLs had increased numbers of CD44(hi), CD62L(lo), KLRG1(+), ICOS(+) short-lived effector cells, indicating an influx of activated T cells. Following oral infection with L. monocytogenes, Rc3h1(gt/gt) → NL chimeras had more liver pathology and greater numbers of bacteria in the Peyer's patches than NL → NL chimeras. These findings demonstrate that small intestinal inflammation in Rc3h1(san/san) and Rc3h1(gt/gt) mice is due to a failure of Roquin expression in the immune system and not to insufficient systemic Roquin expression.

Eosinophilic ascites with marked peripheral eosinophilia: a diagnostic challenge.

Eosinophilic disease of the gastrointestinal tract is rare and is characterized by the presence of gastrointestinal symptoms in association with eosinophilic infiltration of any part of the gastrointestinal tract. Clinical presentation of eosinophilic gastroenteritis (EGE) varies not only by the part of the gastrointestinal tract involved but also with the depth of eosinophilic infiltration of the gut wall. We describe the case of a 41-year-old woman with a history of atopy who presented with severe abdominal pain and diarrhoea. Investigations showed large-volume eosinophil-rich ascites and a markedly elevated peripheral blood eosinophil count and immunoglobulin E level. Bone marrow aspirate, trephine biopsy and T-cell studies showed no evidence of underlying haematological malignancy. Vasculitic disease and parasitic infection were systematically excluded. Colonic and upper gastrointestinal biopsies confirmed a diagnosis of EGE with eosinophilic ascites. The patient was treated with systemic corticosteroids and dietary allergen elimination with dramatic therapeutic response. The diagnostic and therapeutic challenges associated with EGE in its various forms are discussed.

Long-term cysteine fortification impacts cysteine/glutathione homeostasis and food intake in ageing rats.

PURPOSE: Healthy ageing is associated with higher levels of glutathione. The study aimed to determine whether long-term dietary fortification with cysteine increases cysteine and glutathione pools, thus alleviating age-associated low-grade inflammation and resulting in global physiological benefits. METHODS: The effect of a 14-week dietary fortification with cysteine was studied in non-inflamed (NI, healthy at baseline) and in spontaneously age-related low-grade inflamed (LGI, prefrail at baseline) 21-month-old rats. Fifty-seven NI rats and 14 LGI rats received cysteine-supplemented diet (4.0 g/kg of free cysteine added to the standard diet containing 2.8 g/kg cysteine). Fifty-six NI rats and 16 LGI rats received a control alanine-supplemented diet. RESULTS: Cysteine fortification in NI rats increased free cysteine (P < 0.0001) and glutathione (P < 0.03) in the liver and the small intestine. In LGI rats, cysteine fortification increased total non-protein cysteine (P < 0.0007) and free cysteine (P < 0.03) in plasma, and free cysteine (P < 0.02) and glutathione (P < 0.01) in liver. Food intake decreased over time in alanine-fed rats (r² = 0.73, P = 0.0002), whereas it was constant in cysteine-fed rats (r² = 0.02, P = 0.68). Cysteine fortification did not affect inflammatory markers, mortality, body weight loss, or tissue masses. CONCLUSION: Doubling the dietary intake of cysteine in old rats increased cysteine and glutathione pools in selected tissues. Additionally, it alleviated the age-related decline in food intake. Further validation of these effects in the elderly population suffering from age-related anorexia would suggest a useful therapeutic approach to the problem.

Eosinophilic gastrointestinal disorders (EGID) with peripheral eosinophilia: a retrospective review at Mayo Clinic.

BACKGROUND AND AIMS: Hypereosinophilic syndrome (HES) is defined by significant eosinophilia (>1,500 eos/µl), which often leads to end-organ damage/dysfunction. It is unclear if the presence of significant peripheral eosinophilia (>1,500 eos/µl) indicates a more aggressive form of eosinophilic gastrointestinal disorder (EGID). METHODS: A database query of the Mayo Clinic Rochester electronic records (1995-2008) was performed using several search terms for eosinophilic gastrointestinal disease, and 161 records were reviewed. Patients under 18 years age, those without Mayo-reviewed pathology specimens, those with eosinophilic esophagitis only, and/or those with evidence of secondary etiologies for GI eosinophilia were excluded. A total of 39 were found to have primary EGID. We compared individuals with biopsy-proven primary EGID based on whether they had significant peripheral eosinophilia (≥1,500 eos/µl) (group A) or not (group B). RESULTS: Group A tended to have more atopy (A: 12/15; B: 11/24; p = 0.03) and more extensive segmental involvement of the GI tract (p = 0.001). None with available studies had evidence of cardiac (A: 7/15; B: 6/24) or bone marrow (A: 10/15; B: 6/24) involvement. The two thromboembolic events in group A after diagnosis did not translate to significantly greater risk (HR = infinity, p = 0.13; group A vs. B). Doses of initial (A: 40 mg/day; B: 55 mg/day; p = 0.17) and maintenance prednisone (A; 8.75 mg/day; B: 7.5 mg/day; p > 0.90) were similar. Group A was significantly more likely to need maintenance prednisone (77 vs. 8%, p = 0.001), with a median treatment duration of 52 weeks. Recurrence of symptoms (and peripheral eosinophilia) during prednisone taper was common in both groups. Prednisone-sparing agents (hydroxyurea, imatinib mesylate, interferon (IFN)-α2b, anti-interleukin (IL-5) monoclonal antibody) were more commonly used in group A (73 vs. 8%; p < 0.0001). CONCLUSIONS: EGID with peripheral eosinophilia ≥1,500/µl is associated with atopy, greater GI segmental involvement, and uncertain risk of thrombosis. The common use of long-term steroids and variable responsiveness to nonsteroidal agents, particularly in group A, underscores the need for targeted therapies.

Eosinophilic gastroenteritis: clinical manifestations and morphological characteristics, a retrospective study of 42 patients.

OBJECTIVE: To evaluate the clinical manifestations, endoscopic, and radiological characteristics, histological features, and treatment of eosinophilic gastroenteritis in adult patients. METHODS: The clinical records of 34 patients diagnosed as eosinophilic gastroenteritis and eight patients who had abdominal symptoms and unexplained peripheral eosinophilia but no evidence of tissue eosinophilic infiltration were reviewed and analyzed. RESULTS: Thirteen patients had a history of asthma or allergic rhinitis, while 10 had an allergic history. Peripheral eosinophilia occurred in 83.3% of patients, IgE was elevated in half, and α2-macroglobulin was elevated in 92.8% of patients. The small intestine(82.4%)was the most common site involved. Erythema was the predominate feature seen on endoscopy. Radiographic study generally revealed thickening of the small intestinal wall. Eosinophilia generally involved the lamina propria of mucosa, but any layer of the gut could be affected, even in sites which had normal endoscopic or radiographic appearance. In all, 15.4% (6/39) of patients had Helicobacter pylori infection. Symptom remission within 1 week was found in 80% (20/25) of patients treated with steroids and in 58.8% (10/17) of patients treated with symptomatic treatment. In all, 85.7% (18/21) of patients had their eosinophil counts return to normal within 2 weeks in the steroid treatment group, but none (0/13) in the other group. CONCLUSION: Eosinophilic gastroenteritis may be more common than previously recognized. Multiple biopsies obtained from the both normal and abnormal appearing areas in the second part of the duodenum are highly recommended. Steroids are effective in relieving symptoms and improving eosinophilia.

Eosinophilic gastrointestinal disorders in infants: a Japanese case series.

BACKGROUND: Eosinophilic gastrointestinal disorders (EGIDs) are disorders characterized by primary eosinophil inflammation in the gastrointestinal tract. There are a small number of reports of eosinophil infiltration in gastrointestinal tracts presenting as EGIDs in infants. In this study, we present Japanese cases of EGIDs in infants. METHODS: Five patients diagnosed with or strongly suspected to have EGIDs in our hospital from 2008 to 2010 were reviewed. Radiographic contrast enema examinations and/or endoscopies were performed in 4 and 3 patients, respectively. RESULTS: There were patients with eosinophilic colitis (1 suspected and 2 biopsy-proven), a patient who was suspected of having allergic eosinophilic enterocolitis, and a patient with eosinophilic gastroenteritis associated with pediatric hypereosinophilic syndrome. CONCLUSIONS: The causes and clinical findings of patients with intestinal eosinophil inflammation vary. Therefore, deliberate examination and observation are important for patients with infantile EGID.