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1.
Molecules ; 26(9)2021 May 08.
Article in English | MEDLINE | ID: mdl-34066903

ABSTRACT

The effect of effective microorganisms (EM) on internal organ morphology, intestinal morphometry, and serum biochemical activity in Japanese quails under Clostridium perfringens challenge was determined. After 30 days of EM addition, one group of quails was orally inoculated with Clostridium perfringens. The second group did not receive EM and was inoculated with C. perfringens. In the gut, EM supplementation reduced the number of lesions, enhanced gut health, and protected the mucosa from pathogenic bacteria. EM showed an anti-inflammatory effect and fewer necrotic lesions in villi. In the internal organs, EM showed a protective effect against a typical lesion of C. perfringens infection. Necrosis and degeneration of the hepatocytes, necrosis of bile ducts, and bile duct proliferation were more severe in the infected group without EM. Morphometric evaluation showed significantly higher villi in the jejunum after EM addition. A greater crypt depth was observed in the C. perfringens group. Biochemical analysis of the blood indicated lower cholesterol on the 12th day of the experiment and between-group differences in total protein, lactate dehydrogenase (LDH), and albumin levels in the EM group. Further studies are needed to improve EM activity against pathologic bacteria as a potential alternative to antibiotics and to develop future natural production systems.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Bird Diseases/blood , Bird Diseases/diet therapy , Clostridium Infections/blood , Clostridium Infections/diet therapy , Clostridium perfringens , Enteritis/blood , Enteritis/diet therapy , Intestinal Mucosa/microbiology , Probiotics/therapeutic use , Protective Agents/therapeutic use , Quail/blood , Quail/microbiology , Animal Feed/microbiology , Animals , Bile Ducts/pathology , Bird Diseases/microbiology , Cholesterol/blood , Clostridium Infections/microbiology , Enteritis/microbiology , Female , Hepatocytes/pathology , Intestinal Mucosa/pathology , Jejunum/microbiology , Jejunum/pathology , L-Lactate Dehydrogenase/blood , Necrosis , Serum Albumin/analysis , Treatment Outcome
3.
Mod Rheumatol ; 31(3): 643-648, 2021 May.
Article in English | MEDLINE | ID: mdl-32815450

ABSTRACT

OBJECTIVES: Lupus enteritis (LE) is a rare but well-known gastrointestinal manifestation of systemic lupus erythematosus (SLE). This study was conducted to identify prognostic factors associated with poor responses in patients with LE. METHODS: We consecutively registered patients diagnosed with LE between January 2009 and October 2019, and retrospectively compared their clinical characteristics based on whether they had good or poor responses to treatment. RESULTS: A total of 13 patients (17 episodes) were included. The median age was 41 years, and 12 patients were female. A comparison of clinical characteristics between groups revealed similar computed tomography (CT) findings. However, serum CH50 levels were significantly lower in the poor response group (median [interquartile ranges (IQR)]; 29.2 [25.3-46.9] U/mL vs 19.3 [7.8-24.0] U/mL, p = .0095). More patients in the poor response group had higher titers of anti-cardiolipin ß2-glycoprotein I antibody (anti-CL ß2GPI Ab) and were started on glucocorticoids (GCs) at moderate doses. In multivariable analysis, serum CH50 level was independently associated with poor response to induction therapy. CONCLUSION: Lower levels of CH50 at the time of initial treatment predicted inadequate treatment response in patients with LE.


Subject(s)
Complement Hemolytic Activity Assay/standards , Enteritis/drug therapy , Lupus Erythematosus, Systemic/drug therapy , Adult , Autoantibodies/immunology , Enteritis/blood , Enteritis/diagnostic imaging , Female , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Humans , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/diagnostic imaging , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed , beta 2-Glycoprotein I/immunology
4.
Immunol Res ; 68(4): 179-188, 2020 08.
Article in English | MEDLINE | ID: mdl-32621113

ABSTRACT

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.


Subject(s)
CTLA-4 Antigen/metabolism , Enteritis/immunology , Radiation Injuries/immunology , T-Lymphocytes, Regulatory/radiation effects , Uterine Cervical Neoplasms/radiotherapy , Case-Control Studies , Enteritis/blood , Enteritis/diagnosis , Female , Follow-Up Studies , Healthy Volunteers , Humans , Lymphocyte Activation/radiation effects , Radiation Injuries/blood , Radiation Injuries/diagnosis , Severity of Illness Index , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism
5.
Biochem Pharmacol ; 180: 114102, 2020 10.
Article in English | MEDLINE | ID: mdl-32562786

ABSTRACT

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.


Subject(s)
Enteritis/prevention & control , GTP Cyclohydrolase/genetics , Intestines/blood supply , Phenylketonurias/blood , Radiation Injuries/prevention & control , Radiotherapy/adverse effects , Aged , Aged, 80 and over , Animals , Biopterins/analogs & derivatives , Biopterins/pharmacology , Down-Regulation , Endothelium, Vascular/drug effects , Endothelium, Vascular/radiation effects , Enteritis/blood , Enteritis/genetics , Enteritis/pathology , Female , GTP Cyclohydrolase/antagonists & inhibitors , Human Umbilical Vein Endothelial Cells , Humans , Male , Mesenteric Arteries/drug effects , Mesenteric Arteries/radiation effects , Middle Aged , Nitric Oxide Synthase Type III/metabolism , Phenylketonurias/etiology , Radiation Injuries/blood , Radiation Injuries/genetics , Radiation Injuries/pathology , Radiation Injuries, Experimental/blood , Radiation Injuries, Experimental/genetics , Radiation Injuries, Experimental/prevention & control , Rats , Rats, Sprague-Dawley , Vasodilation/drug effects , Vasodilation/radiation effects
6.
J Vet Med Sci ; 82(6): 759-763, 2020 Jun 24.
Article in English | MEDLINE | ID: mdl-32295995

ABSTRACT

Human patients with inflammatory bowel disease may have poor prognosis with hypozincemia. However, there are limited data on zinc concentrations in the blood of dogs with lymphocytic-plasmacytic enteritis (LPE). The purpose of this study was to investigate the serum zinc concentration in dogs with LPE and its influence on disease severity and prognosis. Thirty-five dogs with LPE were recruited. Serum zinc concentration was measured using atomic absorption spectrometry. Hypozincemia was observed in 18/35 (51%) dogs with LPE. Serum zinc concentration was inversely correlated with histological and clinical severities. Overall survivals were significantly shorter in dogs with hypozincemia than in those without it. These findings suggest that serum zinc concentration is a useful biomarker for LPE severity and prognosis in dogs.


Subject(s)
Dog Diseases/blood , Enteritis/veterinary , Zinc/blood , Animals , Biomarkers/blood , Dog Diseases/pathology , Dogs , Enteritis/blood , Enteritis/pathology , Female , Male , Prognosis , Survival Analysis
8.
Metabolomics ; 16(3): 29, 2020 02 24.
Article in English | MEDLINE | ID: mdl-32095917

ABSTRACT

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).


Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/metabolism , Enteritis/metabolism , Biomarkers, Tumor/blood , Case-Control Studies , Chronic Disease , Colorectal Neoplasms/blood , Colorectal Neoplasms/diagnosis , Enteritis/blood , Enteritis/diagnosis , Female , Humans , Male , Metabolomics , Middle Aged , Neoplasm Staging , Phenotype
9.
Saudi J Gastroenterol ; 26(1): 39-45, 2020.
Article in English | MEDLINE | ID: mdl-31997777

ABSTRACT

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.


Subject(s)
Colonic Diseases/blood , Enteritis/blood , Eosinophilia/diagnosis , Eosinophils/pathology , Gastritis/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , Case-Control Studies , Colonic Diseases/pathology , Enteritis/pathology , Eosinophilia/blood , Eosinophilia/pathology , Female , Gastritis/pathology , Humans , Jordan/epidemiology , Leukocyte Count , Male , Middle Aged , ROC Curve , Retrospective Studies , Sensitivity and Specificity , Young Adult
10.
J Vet Intern Med ; 34(2): 691-699, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31919893

ABSTRACT

BACKGROUND: Dogs infected with canine parvovirus (CPV) have compromised intestinal epithelial barrier integrity. Production of D-lactate by enteric bacteria may directly reflect disease severity or contribute to metabolic acid-base status in these dogs. HYPOTHESIS: Serum D-lactate concentration will be increased in CPV dogs compared to healthy controls and correlate with markers of disease severity and acid-base status. ANIMALS: Dogs with CPV undergoing treatment (n = 40) and healthy control dogs (n = 9). METHODS: Prospective observational study. Dogs with CPV had a baseline and daily CBC, venous blood gas with serum electrolyte concentrations, composite clinical severity score, and serum D-lactate concentration performed. A single serum D-lactate measurement was obtained from healthy control dogs. RESULTS: The CPV dogs had a higher D-lactate concentration (mean ± SD) of 469 ± 173 µM compared to controls, 306 ± 45 µM (P < .001). There was no difference in baseline D-lactate concentrations for CPV survivors (474 ± 28 µM), versus nonsurvivors (424 ± 116 µM; P = .70). D-lactate concentration decreased over the first 4 days of treatment (-9.6 µM/d; P = .46). Dogs hospitalized for <4 days had lower baseline D-lactate concentrations compared to those hospitalized ≥4 days (400 ± 178 µM versus 520 ± 152 µM; P = .03). No sustained correlation over time between serum D-lactate concentration and clinical severity score or recorded acid-base results. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum D-lactate concentrations are higher in dogs with CPV compared to healthy controls but do not appear to be clinically relevant. No relationship identified between serum D-lactate concentrations and markers of CPV disease severity, acid-base status, or outcome.


Subject(s)
Dog Diseases/blood , Enteritis/veterinary , Lactic Acid/blood , Parvoviridae Infections/veterinary , Animals , Dogs , Enteritis/blood , Enteritis/virology , Parvoviridae Infections/blood , Parvoviridae Infections/pathology , Prospective Studies
11.
J Allergy Clin Immunol ; 145(1): 255-269, 2020 01.
Article in English | MEDLINE | ID: mdl-31738990

ABSTRACT

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.


Subject(s)
Cytokines , Endoscopy, Gastrointestinal , Enteritis , Eosinophilia , Gastritis , Adolescent , Adult , Biomarkers/blood , Child , Cytokines/blood , Cytokines/immunology , Enteritis/blood , Enteritis/diagnosis , Enteritis/immunology , Enteritis/pathology , Eosinophilia/blood , Eosinophilia/diagnosis , Eosinophilia/immunology , Eosinophilia/pathology , Female , Gastritis/blood , Gastritis/diagnosis , Gastritis/immunology , Gastritis/pathology , Humans , Male
12.
Comp Med ; 69(2): 135-143, 2019 04 01.
Article in English | MEDLINE | ID: mdl-30902119

ABSTRACT

Serum cobalamin and folate concentrations can serve as surrogate markers of gastrointestinal disease in dogs and cats, where they can have diagnostic, therapeutic, and prognostic implications. Chronic disease of the gastrointestinal tract, particularly chronic lymphocytic enteritis (CLE), occurs frequently in captive common marmosets. The aims of this study were to validate a commercially available assay for measuring serum cobalamin and folate concentrations in common marmosets, to establish reference intervals for these analytes in healthy marmosets, and to measure serum concentrations in common marmosets with CLE. The commercial assay was linear, accurate, precise, and reproducible for the measurement of serum cobalamin and folate concentrations in common marmosets. In healthy marmosets, the serum cobalamin concentration ranged from 322 to 2642 pg/mL (n = 35) and serum folate concentration from 54.8 to 786.4 ng/mL (n = 37). Low serum folate concentrations were moderately sensitive (greater than 70%) for CLE, and low serum cobalamin concentrations were moderately (greater than 70%) specific for CLE. Both serum cobalamin and folate concentrations were relatively unchanged in marmosets during 120 to 220 d. Serum cobalamin and folate concentrations were stable for approximately 7 y when samples were stored at -80 °C. Additional studies are warranted to further study the clinical implications of low serum cobalamin and folate concentrations in common marmosets.


Subject(s)
Enteritis/veterinary , Folic Acid/blood , Monkey Diseases/blood , Vitamin B 12/blood , Animals , Biomarkers/blood , Callithrix/blood , Enteritis/blood , Female , Male
13.
Eur J Gastroenterol Hepatol ; 31(2): 157-162, 2019 02.
Article in English | MEDLINE | ID: mdl-30113369

ABSTRACT

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.


Subject(s)
Enteritis/pathology , Eosinophilia/pathology , Eosinophils/pathology , Gastritis/pathology , Abdominal Pain/etiology , Adrenal Cortex Hormones/administration & dosage , Adult , Aged , Anti-Inflammatory Agents/administration & dosage , Biopsy , Disease Progression , Drug Administration Schedule , Endoscopy, Gastrointestinal , Enteritis/blood , Enteritis/complications , Enteritis/drug therapy , Eosinophilia/blood , Eosinophilia/complications , Eosinophilia/drug therapy , Female , Follow-Up Studies , Gastritis/blood , Gastritis/complications , Gastritis/drug therapy , Humans , Male , Middle Aged , Recurrence , Remission Induction , Retrospective Studies , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
14.
Pediatr Neonatol ; 60(4): 377-381, 2019 08.
Article in English | MEDLINE | ID: mdl-30316735

ABSTRACT

BACKGROUND: Febrile children are often evaluated for the risk of bacterial infections in the pediatric emergency department (PER). Hepcidin is an acute phase inflammatory protein. In this study, we examined the plasma hepcidin levels in febrile children. METHODS: This study was conducted at a pediatric emergency department with 123 febrile children. We measured plasma hepcidin levels using an enzyme-linked immunosorbent assay. We further evaluated clinical characteristics and routine blood tests along with the hepcidin levels. RESULTS: We observed significantly higher plasma hepcidin levels in bacterial enteritis (p = 0.026) and combined with urinary tract infection (p = 0.007). Furthermore, hepcidin levels had a significantly positive correlation with CRP level and length of hospital stay (R = 0.296, p = 0.001 and R = 0.213, p = 0.018). Hepcidin levels greater than 65 ng/mL also more accurately predicted bacterial infections than values below 65 ng/mL (11.7% vs. 2.1%, Odds ratio 8.4, 95% confident interval 1.7-40.9, p = 0.002). CONCLUSION: This study provides evidence that febrile children with bacterial infection have higher plasma hepcidin levels, and the values correlated with CRP level and length of hospital stay. Therefore, hepcidin values can potentially be adopted as a biomarker for identifying febrile children with bacterial infection, particularly bacterial enteritis and urinary tract infection.


Subject(s)
Bacterial Infections/blood , Enteritis/blood , Fever/blood , Hepcidins/blood , Urinary Tract Infections/blood , Bacterial Infections/metabolism , Biomarkers/blood , Biomarkers/metabolism , C-Reactive Protein/metabolism , Child, Preschool , Emergency Service, Hospital , Enteritis/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Fever/metabolism , Humans , Infant , Length of Stay , Male , Urinary Tract Infections/metabolism
15.
Eur J Nutr ; 58(7): 2859-2873, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30284595

ABSTRACT

PURPOSE: Beta-glucans are biologically active polysaccharides having antioxidant, immunomodulatory, and antiinflammatory properties. This study investigated the transcriptomic profile in peripheral blood of rats with LPS-induced enteritis, which were fed a diet supplemented with high- (G1) and low- (G2) molecular-weight oat beta-glucans. METHODS: Two-color rat gene expression microarrays were applied and the analysis was performed using a common reference design to provide easy means of comparing samples from various experimental conditions against one another. Common reference sample was labeled with cyanine 3 (Cy3) and investigated samples from each experimental group: C-G0 (control group fed semi-synthetic diet), LPS-G0 (LPS-challenged group fed semi-synthetic diet), LPS-G1 (LPS-challenged group fed G1 beta-glucan enriched diet), and LPS-G2 (LPS-challenged group fed G2 beta-glucan enriched diet) were labeled with cyanine 5 (Cy5). Each microarray was performed in quadruplicate. Statistical analysis was performed using one-way ANOVA and Tukey's HSD post-hoc test (p < 0.05). A multiple testing correction was performed using Benjamini and Hochberg False Discovery Rate < 5%. A quantitative real-time RT-PCR was performed to verify the expression of chosen transcripts. RESULTS: The microarray analyses revealed differentially expressed transcripts between: the LPS-G0 and the control groups: C-G0 (138 genes), the LPS-G1 and LPS-G0 groups (533 genes), and the LPS-G2 and LPS-G0 groups (97 genes). Several differentially expressed genes in the beta-glucan-supplemented groups encoded proteins belonging to TLR and NLR signaling pathways, as well as prostaglandin synthesis and regulation pathways. Both beta-glucans up-regulated the expression of Atg10, which belongs to the family of autophagy-related genes, suggesting a possible link between autophagy induction and beta-glucan supplementation. CONCLUSION: The changes in gene expression observed in the peripheral blood indicate that oat beta-glucans exerted a protective effect in rats with an induced inflammatory state caused by LPS challenge. The greater number of differentially expressed genes was observed in group supplemented with G1 beta-glucan, pointing at the differences in the mode of action of high- and low-molecular-weight beta-glucans in the organism.


Subject(s)
Avena , Enteritis/immunology , Gene Expression Regulation/drug effects , beta-Glucans/pharmacokinetics , Administration, Oral , Animal Feed , Animals , Disease Models, Animal , Enteritis/blood , Enteritis/diet therapy , Gene Expression Regulation/immunology , Immunity , Lipopolysaccharides , Male , Molecular Weight , Rats , Rats, Sprague-Dawley , beta-Glucans/administration & dosage , beta-Glucans/blood
16.
Am J Clin Nutr ; 108(4): 889-896, 2018 10 01.
Article in English | MEDLINE | ID: mdl-30247538

ABSTRACT

Background: Adverse birth outcomes, including preterm birth and stunting at birth, have long-term health implications. The relation between adverse birth outcomes and chronic, asymptomatic gastrointestinal inflammation (environmental enteric dysfunction-EED) is poorly understood. Objective: We aimed to examine the relation between maternal EED and adverse birth outcomes in a sample of pregnant Ugandan women and their newborn infants. Design: We conducted a prospective cohort study in Mukono, Uganda. A total of 258 pregnant women were enrolled at their first prenatal visit (∼18 weeks of gestation). EED was measured by urinary lactulose:mannitol (L:M) ratio and serum concentrations of antibodies to the bacterial components flagellin and LPS. Covariates were obtained from survey data collected at 2 time points. Associations were assessed through the use of unadjusted and adjusted simple linear regression models. Results: Complete birth outcome data were recorded for 220 infants within 48 h of delivery. Mean ± SD gestational age was 39.7 ± 2.1 wk, and 7% were born preterm. Mean ± SD length and length-for-age z score (LAZ) at birth were 48.1 ± 3.2 cm and -0.44 ± 1.07, respectively. L:M ratio was not associated with any birth outcome. In adjusted models, higher concentrations of natural log-transformed anti-flagellin immunoglobin G (IgG) and anti-LPS IgG were significantly associated with shorter length of gestation (ß: -0.89 wk; 95% CI: -1.77, -0.01 wk, and ß: -1.01 wk; 95% CI: -1.87, -0.17 wk, respectively) and with reduced length (ß: -0.80 cm; 95% CI: -1.55, -0.05 cm, and ß: -0.79 cm; 95% CI: -1.54, -0.04 cm, respectively) and LAZ at birth (ß -0.44 z score; 95% CI: -0.83, -0.05, and ß: -0.40 z score; 95% CI: -0.79, -0.01, respectively). Conclusion: Maternal anti-flagellin and anti-LPS IgG concentrations in pregnancy, but not L:M ratio, were associated with shorter gestation and reduced infant length at birth. Further research on the relation between maternal EED and birth outcomes is warranted.


Subject(s)
Body Height , Enteritis/physiopathology , Fetal Development , Gestational Age , Inflammation/complications , Pregnancy Complications/physiopathology , Premature Birth/etiology , Adult , Antibodies/blood , Enteritis/blood , Enteritis/complications , Female , Flagellin , Growth Disorders/etiology , Humans , Immunoglobulin G/blood , Infant, Newborn , Intestine, Small/pathology , Intestine, Small/physiopathology , Lactulose/urine , Lipopolysaccharides , Mannitol/urine , Pregnancy , Pregnancy Complications/pathology , Prospective Studies , Uganda , Young Adult
17.
Cardiovasc Res ; 114(2): 226-232, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29206916

ABSTRACT

Systemic inflammation, induced by disease or experimental intervention, is well established to result in elevated levels of circulating triglycerides, and reduced levels of high-density lipoprotein-cholesterol (HDL-C), in most mammalian species. However, the relationship between inflammation and low-density lipoprotein-cholesterol (LDL-C) concentrations is less clear. Most reports indicate that systemic inflammation, as observed during sepsis or following high dose experimental endotoxaemia, lowers total, and LDL-C in man. However, isolated reports have suggested that certain inflammatory conditions are associated with increased LDL-C. In this review, we summarize the emerging evidence that low-grade inflammation specifically of intestinal origin may be associated with increased serum LDL-C levels. Preliminary insights into potential mechanisms that may mediate these effects, including those connecting inflammation to trans-intestinal cholesterol efflux (TICE), are considered. We conclude that this evidence supports the potential downregulation of major mediators of TICE by inflammatory mediators in vitro and during intestinal inflammation in vivo. The TICE-inflammation axis therefore merits further study in terms of its potential to regulate serum LDL-C, and as a readily druggable target for hypercholesterolaemia.


Subject(s)
Acute-Phase Reaction/blood , Cholesterol, LDL/blood , Enteritis/blood , Enterocytes/metabolism , Inflammation Mediators/blood , Intestine, Small/metabolism , Acute-Phase Reaction/drug therapy , Acute-Phase Reaction/immunology , Acute-Phase Reaction/microbiology , Animals , Anti-Inflammatory Agents/pharmacology , Cholesterol, HDL/blood , Enteritis/drug therapy , Enteritis/immunology , Enteritis/microbiology , Enterocytes/drug effects , Enterocytes/immunology , Enterocytes/microbiology , Gastrointestinal Microbiome , Humans , Hypolipidemic Agents/pharmacology , Intestine, Small/drug effects , Intestine, Small/immunology , Intestine, Small/microbiology , Triglycerides/blood
18.
Pak J Pharm Sci ; 30(5(Special)): 1851-1855, 2017 Sep.
Article in English | MEDLINE | ID: mdl-29084657

ABSTRACT

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.


Subject(s)
Azithromycin/therapeutic use , Enteritis/drug therapy , Pefloxacin/therapeutic use , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Azithromycin/adverse effects , C-Reactive Protein/metabolism , Enteritis/blood , Enteritis/metabolism , Female , Humans , Interleukin-6/blood , Male , Middle Aged , Pefloxacin/adverse effects , Time Factors , Young Adult
19.
Int Urol Nephrol ; 49(12): 2205-2216, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28956241

ABSTRACT

PURPOSE: To investigate the predictive value of procalcitonin (PCT) in patients with stage 1-4 and stage 5 chronic kidney disease (CKD). METHODS: Five hundred and forty-one CKD inpatients were retrospectively analyzed and divided into CKD stage 1-4 (CKD1-4) and CKD stage 5 (CKD5) groups. Each group was further divided into non-infection, local infection, and sepsis subgroups. The clinical characteristics and inflammatory indexes of each subgroup including PCT, C-reactive protein (CRP), white blood cell count (WBC), and neutrophil percentage (N%) were compared, and the receiver operating characteristic curves to predict local infection and sepsis were plotted. RESULTS: Our research showed that the incidence and severity of infection in CKD5 group were significantly higher than those of CKD1-4 group; the baseline PCT level in CKD patients increased as renal function decreased and strongly correlated with CKD staging (r = 0.749); for CKD1-4 group, PCT, WBC, and N% could predict sepsis with the area under the curve (AUC) of 0.956, 0.854, and 0.917, respectively, but only CRP could predict local infection with AUC of 0.729, and for CKD5 group, only PCT and CRP could predict local infection with AUC of 0.715 and 0.780, respectively, and only PCT and N% could predict sepsis with AUC of 0.823 and 0.683, respectively. CONCLUSIONS: The baseline PCT level of CKD patients is negatively correlated with renal function. In both CKD1-4 and CKD5 patients, the predictive value of PCT for local infection is not as good as that of CRP, while it has a significant advantage in predicting sepsis.


Subject(s)
Calcitonin/blood , Infections/blood , Infections/diagnosis , Neutrophils , Renal Insufficiency, Chronic/blood , Adult , Aged , Aged, 80 and over , Area Under Curve , Biomarkers/blood , C-Reactive Protein/metabolism , Catheter-Related Infections/blood , Catheter-Related Infections/complications , Catheter-Related Infections/diagnosis , Community-Acquired Infections/blood , Community-Acquired Infections/complications , Community-Acquired Infections/diagnosis , Enteritis/blood , Enteritis/complications , Enteritis/diagnosis , Female , Humans , Infections/complications , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Leukocyte Count , Male , Middle Aged , Peritonitis/blood , Peritonitis/complications , Peritonitis/diagnosis , Pneumonia/blood , Pneumonia/complications , Pneumonia/diagnosis , Predictive Value of Tests , ROC Curve , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/physiopathology , Retrospective Studies , Sepsis/blood , Sepsis/complications , Sepsis/diagnosis , Severity of Illness Index , Urinary Tract Infections/blood , Urinary Tract Infections/complications
20.
Intern Med ; 56(21): 2819-2825, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-28943560

ABSTRACT

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.


Subject(s)
Cytokines/blood , Enteritis/blood , Eosinophilia/blood , Eosinophilic Esophagitis/blood , Gastritis/blood , Biomarkers , Chemokine CCL19/blood , Chemokine CXCL12/blood , Chemokines/blood , Chemokines/immunology , Cytokines/immunology , Enteritis/immunology , Eosinophilia/immunology , Eosinophilic Esophagitis/immunology , Female , Gastritis/immunology , Humans , Interleukin-33/blood , Male , Middle Aged , Thymic Stromal Lymphopoietin
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