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Fecal leukocytes, in intestinal disorders [keywords]
- Effect of yeast cell product (CitriStim) supplementation on broiler performance and intestinal immune cell parameters during an experimental coccidial infection. [Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't]
- Poult Sci 2013 Feb; 92(2):358-63.
This experiment studied the effects of whole yeast cell product supplementation on broiler production parameters, fecal coccidial oocyst counts, and local and systemic immune parameters following an experimental coccidial infection. Birds were fed 0, 0.1, or 0.2% whole yeast cell product (CitriStim). At 21 d of age, birds were challenged with live coccidial oocysts. Supplementation with whole yeast cell product increased BW gain between 0 and 12 d (P = 0.01) postcoccidial challenge. Birds supplemented with 0.2% Citristim had better (P = 0.01) feed efficiency between 0 and 12 d postcoccidial infection. Supplementation with whole yeast cell product decreased (P = 0.01) the fecal coccidial oocyst count at 7 d postcoccidial challenge. Citristim supplementation at 0.2% increased (P < 0.01) macrophage nitric oxide production by 93 and 193% at 5 and 12 d postcoccidial challenge. Supplementation with whole yeast cell product at 0.2% increased cecal tonsil interleukin-1 mRNA amounts approximately 4.5- and 3.7-fold at 5 and 12 d postcoccidial challenge, respectively, over the group with no whole yeast cell product supplementation. Citristim supplementation downregulated cecal tonsil interleukin-10 mRNA amounts compared with the unsupplemented groups at both 5 (P = 0.01) and 12 d (P < 0.01) postcoccidial challenge. Supplementation with whole yeast cell product did not alter (P > 0.05) serum anticoccidial IgG contents or cecal tonsil CD4(+) and CD8(+) cell percentages at 5 and 12 d postcoccidial infection. It could be concluded that supplementing whole yeast cell product (CitriStim) to broiler diets can improve production parameters, decrease fecal oocyst count, and increase inflammatory cytokine production postcoccidial infection.
- Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- PLoS Pathog 2012; 8(11):e1003000.
Idiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus monkeys kept in captivity. Here, we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency, accompanied by weight gain, in four out of the five treated monkeys. By flow cytometry analysis of pinch biopsies collected during colonoscopies before and after treatment, we found an induction of a mucosal T(H)2 response following helminth treatment that was associated with a decrease in activated CD4(+) Ki67+ cells. In parallel, expression profiling with oligonucleotide microarrays and real-time PCR analysis revealed reductions in T(H)1-type inflammatory gene expression and increased expression of genes associated with IgE signaling, mast cell activation, eosinophil recruitment, alternative activation of macrophages, and worm expulsion. By quantifying bacterial 16S rRNA in pinch biopsies using real-time PCR analysis, we found reduced bacterial attachment to the intestinal mucosa post-treatment. Finally, deep sequencing of bacterial 16S rRNA revealed changes to the composition of microbial communities attached to the intestinal mucosa following helminth treatment. Thus, the genus Streptophyta of the phylum Cyanobacteria was vastly increased in abundance in three out of five ICD monkeys relative to healthy controls, but was reduced to control levels post-treatment; by contrast, the phylum Tenericutes was expanded post-treatment. These findings suggest that helminth treatment in primates can ameliorate colitis by restoring mucosal barrier functions and reducing overall bacterial attachment, and also by altering the communities of attached bacteria. These results also define ICD in monkeys as a tractable preclinical model for ulcerative colitis in which these effects can be further investigated.
- The value of fecal calprotectin as a marker of intestinal inflammation in patients with ulcerative colitis. [Comparative Study, Journal Article, Research Support, Non-U.S. Gov't]
- Turk J Gastroenterol 2012; 23(5):509-14.
To assess intestinal inflammation, simple, inexpensive and objective tools are desirable in inflammatory bowel disease. This study aimed to evaluate fecal calprotectin as a marker of active disease in ulcerative colitis.Sixty patients with a diagnosis of ulcerative colitis and 20 controls were recruited into the study. The disease activity of ulcerative colitis was determined by modified Truelove-Witts criteria and Rachmilewitz endoscopic index. The enzyme-linked immunosorbent assay was used to measure the concentrations of fecal calprotectin. C-reactive protein, erythrocyte sedimentation rate and hemogram were also measured, and inflammatory markers were compared with fecal calprotectin in determining disease activity.Fecal calprotectin concentration in the patients with active ulcerative colitis (n=30) was significantly higher than that in the inactive ulcerative colitis group (n=30) and in the controls (n=20) (95% confidence interval: 232.5 (0.75-625) vs 11.7 (0.2-625), 7.5 (0.5-512) mg/L, p<0.001). There was no significant difference between the patients with inactive ulcerative colitis and controls (p>0.05). The calprotectin concentration was greater in the patients with a more severe clinical index, higher endoscopic activity (>4), elevated C-reactive protein, leukocytosis, and extensive colitis (p<0.05). The areas under the curve of the receiver operating characteristics were 0.817, 0.809, 0.532, and 0.507 for C-reactive protein, fecal calprotectin, leukocyte count, and erythrocyte sedimentation rate, respectively. There was a significant correlation between the fecal calprotectin concentration and the endoscopic activity in ulcerative colitis (r = 0.548, p<0.001).Fecal calprotectin is a useful marker in the diagnosis of active disease and evaluation of clinical and endoscopic activity in ulcerative colitis.
- Synbiotic therapy decreases microbial translocation and inflammation and improves immunological status in HIV-infected patients: a double-blind randomized controlled pilot trial. [Comparative Study, Journal Article, Randomized Controlled Trial]
- Nutr J 2012.:90.
HIV-infection results in damage and dysfunction of the gastrointestinal system. HIV enteropathy includes pronounced CD4+ T-cell loss, increased intestinal permeability, and microbial translocation that promotes systemic immune activation, which is implicated in disease progression. A synbiotic is the combination of probiotics and prebiotics that could improve gut barrier function. Our study goal was to determine whether the use of a synbiotic, probiotics or a prebiotic can recover immunological parameters in HIV-infected subjects through of a reduction of microbial translocation and pro-inflammatory cytokine production.A randomized, double-blind controlled study was performed; twenty Antiretroviral treatment-naïve HIV-infected subjects were subgrouped and assigned to receive a synbiotic, probiotics, a prebiotic, or a placebo throughout 16 weeks.We had no reports of serious adverse-events. From baseline to week 16, the synbiotic group showed a reduction in bacterial DNA concentrations in plasma (p = 0.048). Moreover, the probiotic and synbiotic groups demonstrated a decrease in total bacterial load in feces (p = 0.05). The probiotic group exhibited a significant increment of beneficial bacteria load (such as Bifidobacterium; p = 0.05) and a decrease in harmful bacteria load (such as Clostridium; p = 0.063). In the synbiotic group, the CD4+ T-cells count increased (median: +102 cells/μL; p = 0.05) and the level of Interleukin 6 cytokine decreased significantly (p = 0.016).Our study showed a significant increase in CD4+ T lymphocyte levels in the synbiotic group, which could delay the initiation of antiretroviral therapy and decrease costs in countries with limited resources.
- Lymphotoxin alpha-deficient mice clear persistent rotavirus infection after local generation of mucosal IgA. [Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, U.S. Gov't, Non-P.H.S.]
- J Virol 2013 Jan; 87(1):524-30.
Rotavirus is a major cause of pediatric diarrheal illness worldwide. To explore the role of organized intestinal lymphoid tissues in infection by and immunity to rotavirus, lymphotoxin alpha-deficient (LTα(-/-)) mice that lack Peyer's patches and mesenteric lymph nodes were orally infected with murine rotavirus. Systemic rotavirus was cleared within 10 days in both LTα(-/-) and wild-type mice, and both strains developed early and sustained serum antirotavirus antibody responses. However, unlike wild-type mice, which resolved the intestinal infection within 10 days, LTα(-/-) mice shed fecal virus for approximately 50 days after inoculation. The resolution of fecal virus shedding occurred concurrently with induction of intestinal rotavirus-specific IgA in both mouse strains. Induction of intestinal rotavirus-specific IgA in LTα(-/-) mice correlated with the (late) appearance of IgA-producing plasma cells in the small intestine. This, together with the absence of rotavirus-specific serum IgA, implies that secretory rotavirus-specific IgA was produced locally. These findings indicate that serum IgG responses are insufficient and imply that local intestinal IgA responses are important for the clearance of rotavirus from intestinal tissues. Furthermore, they show that while LTα-dependent lymphoid tissues are important for the generation of IgA-producing B cells in the intestine, they are not absolutely required in the setting of rotavirus infection. Moreover, the induction of local IgA-producing B cell responses can occur late after infection and in an LTα-independent manner.
- Prevalence, molecular characteristics and risk factors for cryptosporidiosis among Iranian immunocompromised patients. [Journal Article]
- Microbiol Immunol 2012 Dec; 56(12):836-42.
Cryptosporidium spp. is a major cause of diarrhea in developing countries, mainly affecting people with compromised immune systems in general and HIV-infected individuals with low CD4 + T-cell counts in particular. This infection is self-limiting in healthy persons; however, it can be severe, progressive and persistent in those who are immunocompromised. There are few published studies concerning cryptosporidiosis and Cryptosporidium genotypes in Iranian immunocompromised patients and none of them describe risk factors. This study was undertaken to identify prevalence, genotypes and risk factors for cryptosporidiosis in immunocompromised patients. Three fecal samples were obtained at two day intervals from each of the 183 patients and processed with modified Ziehl-Neelsen staining methods and 18S rRNA gene amplification and sequencing. The overall infection prevalence was 6%. Cryptosporidium parvum was identified in isolates from five HIV-infected patients, one patient who had undergone bone marrow transplantation and one with chronic lymphocytic leukemia. Cryptosporidium hominis was identified in isolates from two HIV-infected patients and two patients with acute lymphocytic leukemia. According to univariate analysis, the statistically significant factors were diarrhea (OR = 21.7, CI = 2.83-78.4, P= 0.003), CD4 + lymphocytes less than 100 cells/mm(3) (OR = 41.3, CI = 13.45-114.8, P < 0.0001), other microbial infections (OR = 7.1321.7, CI = 1.97-25.73, P = 0.006), weight loss (OR = 73.78, CI = 15.5-350, P < 0.0001), abdominal pain (OR = 10.29, CI = 2.81-37.74.4, P= 0.001), dehydration (OR = 72.1, CI = 17.6-341.5, P < 0.0001), vomiting (OR = 4.87, CI = 1.4-16.9, P= 0.015), nausea (OR = 9.4, CI = 2.38-37.2, P < 0.001), highly active antiretroviral therapy (OR = 0.089, CI = 0.01-0.8, P= 0.015) and diarrhea in household members (OR = 7.37, CI = 2.04-26.66, P= 0.001). After multivariate analysis and a backward deletion process, only < 100 CD4 + T-lymphocytes/mm(3) maintained a significant association with infection. The authors recommend that this infection should be suspected in patients with diarrhea, weight loss and dehydration in general and in diarrheal individuals with < 100 CD4 + T-lymphocytes/mm(3).
- [Survey on Blastocystis hominis infection in HIV positive individuals in Fuyang City, Anhui Province]. [English Abstract, Journal Article]
- Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2012 Jun; 24(3):303-6, 310.
To understand the epidemiological characteristics of co-infection of HIV and Blastocystis hominis and its risk factors.A total of 309 people with HIV positive in the development zone of Fuyang City were recruited, and the face to face questionnaires were conducted to collect the information of behavioral characteristics and sociodemographic data of the participants. Meanwhile, the samples of stool and blood were collected to test B. hominis, cytokines and CD4+/CD8+ T-lymphocyte. The influencing factors of co-infection of HIV and Blastocystis hominis were analyzed by the single factor analysis and Logistic regression analysis.Among the 309 people involved, 302 accepted feces examinations, 286 accepted the questionnaire investigation, and 263 accepted both of them. The infection rate of B. hominis was 17.11%, that of the female was 21.90%, which was significantly higher than that of the male (11.90%) (P < 0.05). The results from the multivariate Logistic regression model showed that good nutrition was significantly associated with the co-infection of HIV and B. hominis (OR = 0.263, 95% CI: 0.073, 0.945).The infection rate of B. hominis is high in people with HIV positive, and the nutrition situation of individuals may be one of the important risk factors associated with co-infection.
- [Fecal calprotectin: a diagnostic tool for inflammatory bowel disease]. [English Abstract, Journal Article]
- Rev Med Suisse 2012 Sep 5; 8(352):1669-70, 1672-3.
Fecal calprotectin (FC) is a valid biomarker to discriminate with a good sensitivity and specificity the presence of mucosal lesions of the gastrointestinal tube (e.g. ulcers in the context of inflammatory bowel disease (IBD)) from functional disorders (e.g. irritable bowel syndrome). FC is not specific for IBD and can be elevated also in gastrointestinal infections, ischemic colitis or neoplasia. An elevated FC should stimulate further investigations, notably an endoscopic workup. The level of FC correlates with the endoscopic score in Crohn's disease and ulcerative colitis. The correlation of FC and the endoscopic severity is better than the one of CRP or blood leukocytes. Thus, FC can also be used in the follow-up of IBD patients.
- Malaria and helminthic co-infection among HIV-positive pregnant women: prevalence and effects of antiretroviral therapy. [Journal Article, Research Support, Non-U.S. Gov't]
- Acta Trop 2012 Dec; 124(3):179-84.
The impact of malaria on anemia and the interplay with helminths underline the importance of addressing the interactions between HIV/AIDS, malaria and intestinal helminth infections in pregnancy. The aim of this study was to determine the prevalence of malaria-helminth dual infections among HIV positive pregnant mothers after 12 months of ART. A cross sectional study was conducted on intestinal helminths and malaria dual infections among HIV-positive pregnant women attending antenatal health centers in Rwanda. Stool and malaria blood slide examinations were performed on 328 women residing in rural (n=166) and peri-urban locations (n=162). BMI, CD4 cell count, hemoglobin levels, type of ART and viral load of participants were assessed. Within the study group, 38% of individuals harbored helminths, 21% had malaria and 10% were infected with both. The most prevalent helminth species were Ascaris lumbricoides (20.7%), followed by Trichuris trichiura (9.2%), and Ancylostoma duodenale and Necator americanus (1.2%). Helminth infections were characterized by low hemoglobin and CD4 counts. Subjects treated with a d4T, 3TC, NVP regimen had a reduced risk of T. trichiura infection (OR, 0.27; 95% CIs, 0.10-0.76; p<0.05) and malaria-helminth dual infection (OR, 0.29; 95% CI, 0.11-0.75; p<0.05) compared to those receiving AZT, 3TC, NVP. This study shows a high prevalence of malaria and helminth infection among HIV-positive pregnant women in Rwanda. The differential effect of ARTs on the risk of helminth infection is of interest and should be examined prospectively in larger patient groups.
- Safety and efficacy of antigen-specific regulatory T-cell therapy for patients with refractory Crohn's disease. [Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't]
- Gastroenterology 2012 Nov; 143(5):1207-17.e1-2.
New therapeutic strategies are needed for patients with refractory Crohn's disease (CD). We evaluated data from the Crohn's And Treg Cells Study (CATS1) to determine the safety and efficacy of antigen-specific T-regulatory (Treg) cells for treatment of patients with refractory CD.We performed a 12-week, open-label, multicenter, single-injection, escalating-dose, phase 1/2a clinical study in 20 patients with refractory CD. Ovalbumin-specific Treg cells (ova-Tregs) were isolated from patients' peripheral blood mononuclear cells (PBMCs), exposed to ovalbumin, and administrated intravenously. Safety and efficacy were assessed using clinical and laboratory parameters. We evaluated proliferation of PBMCs in response to ovalbumin.Injections of ova-Tregs were well tolerated, with 54 adverse events (2 related to the test reagent) and 11 serious adverse events (3 related to the test reagent, all recovered). Overall, a response, based on a reduction in Crohn's Disease Activity Index (CDAI) of 100 points, was observed in 40% of patients at weeks 5 and 8. Six of the 8 patients (75%) who received doses of 10(6) cells had a response at weeks 5 and 8, with a statistically significant reduction in CDAI. In this group, remission (based on CDAI ≤150) was observed in 3 of 8 patients (38%) at week 5 and 2 of 8 patients (25%) at week 8.Administration of antigen-specific Tregs to patients with refractory CD (CATS1) was well tolerated and had dose-related efficacy. The ovalbumin-specific immune response correlated with clinical response, supporting immune-suppressive mechanisms of ova-Tregs. The consistency of results among different assessment methods supports the efficacy of ova-Tregs; this immune therapy approach warrants further clinical and mechanistic studies in refractory CD. Eudract, Number: 2006-004712-44.