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Mucosal Levels (mucosal + level)

Distribution by Scientific Domains

Medical Sciences	81%

Selected Abstracts

Comparative evaluation of intranasal and subcutaneous route of immunization for development of mucosal vaccine against experimental tuberculosis

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2005
Pramod K. Giri
Abstract Activation of mucosal immunity in the respiratory tract is crucial for protection against respiratory infections. Whether the intranasal route of vaccination imparts better protection against pulmonary tuberculosis than that of subcutaneous vaccination remains a debatable issue. In this study, we have investigated the effect of the routes of immunization on the induction of immunoprotection against experimental tuberculosis employing mycobacterial culture filtrate proteins complexed with dimethyldioctadecylammonium bromide. Vaccination via intranasal and subcutaneous routes triggered immune activation in the spleen and cervical lymph node, while the former route of vaccination lead to higher antigen-specific lymphocyte proliferation, interferon-,, interleukin-12 and interleukin-4 responses in cervical lymph node and induction of antigen-specific IgA responses at mucosal level of the respiratory tract. Mice vaccinated via the intranasal route were found to be better protected against experimental tuberculosis particularly in lung compared to subcutaneous-immunized mice. These results emphasize the importance of the intranasal route vaccination in tuberculosis. [source]

Peroxiredoxin I protects gastric mucosa from oxidative injury induced by H. pylori infection

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2008
Daisuke Sato
Abstract Background and Aim:, Helicobacter pylori (H. pylori) infection enhances the production of reactive oxygen species and peroxynitrite, thereby resulting in oxidative tissue damage. In this study, we examined the role of peroxiredoxin I (Prx I), a stress-induced antioxidant enzyme, in protecting gastric mucosa from H. pylori -induced gastric mucosal injury. Methods:, Wild type (Prx I+/+) and Prx I-deficient type (Prx I,/,) mice were maintained for 2 to 12 months with or without infection of H. pylori, Sydney strain-1. Gastric mucosal expression of Prx I was assessed by immunoblot analysis and immunohistochemistry. The degree of gastritis was evaluated by the updated Sydney system and by mucosal levels of inflammatory cytokines (MIP-2, IL-1,, and TNF-,). Oxidative DNA injury and apoptosis were analyzed by mucosal level of 8-hydroxy-2,-deoxyguanosine, and the number of apoptotic cells stained with a single-stranded DNA antibody, respectively. Results:,H. pylori infection upregulated gastric mucosal Prx I expression in the Prx I+/+ but not the Prx I,/, mice. H. pylori infection also induced more severe gastritis and a more prominent increase in MIP level, more marked oxidative DNA injury, and apoptosis in the Prx I,/, than the Prx I+/+ mice. In the absence of H. pylori infection, no changes were demonstrated in gastric mucosa in either the Prx I+/+ or the Prx I,/, mice. Conclusion:, These data suggest that H. pylori infection upregulates gastric mucosal Prx I expression, and further, that Prx I plays an important role in gastric mucosal protection against oxidative injury induced by H. pylori infection. [source]

Host cell-mediated responses to infection with Cryptosporidium

PARASITE IMMUNOLOGY, Issue 12 2000
V. McDonald
The coccidian Cryptosporidium infects epithelial cells of a variety of vertebrate hosts and is the causative agent of cryptosporidiosis. In mammals, including humans and domestic animals, C. parvum infects the gastrointestinal tract producing an acute watery diarrhoea and weight loss. CD4+ T-cell-deficient hosts have increased susceptibility to infection with the parasite and may develop severe life-threatening complications. The host responses which induce protective immunity and contribute to pathogenesis are poorly understood. In the immunological control of infection, recent studies with murine infection models suggest that IFN-, plays a key role in a partially protective innate immunity against infection identified in immunocompromised mice and also in the elimination of infection mediated by CD4+ T-cells. At the mucosal level, CD4+ intraepithelial lymphocytes are involved in the control of cryptosporidial infection, acting at least in part through production of IFN-, which has a direct inhibitory effect on parasite development in enterocytes. Primary infection of ruminants induces an intestinal inflammatory response in which increased numbers of various T-cell subpopulations appear in the villi. In addition, infection results in increased intestinal expression of pro-inflammatory cytokines such as IL-12, IFN-, and TNF-,. Because these cytokines appear to be important in the aetiology of inflammatory bowel disease, it is possible that they are involved in the mucosal pathogenesis of cryptosporidiosis. [source]

Microbial community diversity associated with the intestinal mucosa of farmed rainbow trout (Oncoryhnchus mykiss Walbaum)

AQUACULTURE RESEARCH, Issue 9 2009
Daniel L Merrifield
Abstract Bacterial communities from the intestinal tract of rainbow trout were investigated to assess transient and resident microbial communities using both culture-based and culture-independent techniques. Viable counts attached to the intestinal mucosa were in the range of log 4.77,5.38 and log 6.67,6.79 CFU g,1 in the intestinal contents. Pseudomonas spp. and Enterobacteriaceae constituted nearly 80% of the allochthonous population but <60% of the autochthonous populations. This coincided with an elevated mucosal level of a group of Gram-positive rods from ,2% in the digesta to 25,35% on the mucosa. This group was identified by 16S rRNA as Arthrobacter aurescens and Janibacter spp. HTCC2649. Analysis of denaturing gradient gel electrophoresis banding patterns showed complex communities in all intestinal regions. Similarity coefficients showed that mucosal communities were ,70% similar to digesta communities and yet due to the presence of bands found uniquely either in the digesta or on the mucosa, the communities are distinctly different. Scanning electron microscopy confirmed mucosal bacterial populations and highlighted a possible localized colonization between mucosal folds. The study highlights the complexity of resident microbial communities that have not been fully explored in previous rainbow trout studies; this is especially true with probiotic/prebiotic investigations. [source]

Five-year results of fixed implant-supported rehabilitations with distal cantilevers for the edentulous mandible

CLINICAL ORAL IMPLANTS RESEARCH, Issue 6 2009
German O. Gallucci
Abstract Objectives: The purpose of this study was to evaluate the survival rate, success rate and primary complications associated with mandibular fixed implant-supported rehabilitations with distal cantilevers over 5 years of function. Material and methods: In this prospective multi-center trial, 45 fully edentulous patients were treated with implant-supported mandibular hybrid prostheses with distal extension cantilevers. Data were collected at numerous time points, including but not limited to: implant placement, abutment placement, final prosthesis delivery, 3 months and 5 years post-loading. Biological, implant and prosthetic parameters defining survival and success were evaluated for each implant including: sulcus bleeding ndex (SBI) at four sites per implant, width of facial and lingual keratinized gingiva (mm), peri-implant mucosal level (mid-facial from the top of the implant collar, measured in mm), modified plaque index (MPI) at four sites per implant, mobility and peri-implant radiolucency. Survival was defined as implants or prostheses that did not need to be replaced. Success rate was defined as meeting well-established criteria that were chosen to indicate healthy peri-implant mucosa osseointegration, prostheses success and complications. Results: A total of 237 implants in 45 completely edentulous patients were included in the study. In each patient, four to six implants were placed to support hybrid prostheses with distal cantilevers. Cantilevers ranged in length from 6 to 21 mm, with an average length of 15.6 mm. The ages of the patients ranged from 34 to 78 with a mean age of 59.5 years. The survival rate of implants was 100% (237/237) and for prostheses 95.5% (43/45). The overall treatment success rate was calculated as 86.7% (39/45). Of the six patients that have not met the criteria for success, two patients required replacement of the entire prosthesis and four patients presented >four complications events. Conclusion: Fixed implant-supported rehabilitation with distal cantilever resulted in a reliable treatment modality over the 5-year observation period. Although biological parameters of MPI, SBI, keratinized tissue and peri-implant mucosal levels showed statistically significant differences over time, the mean values for each patient remained within the normal limits of oral health. Complications were categorized as biological or technical. The majority of complications were technical complications (54/79) and of these most involved fracture of the acrylic teeth and base (20/54). While the survival rate was 100% for implants and 95.5% for prostheses, the application of strict criteria for treatment success resulted in an overall treatment success rate of 86.7%. [source]

Efficient mucosal delivery of the HIV-1 Tat protein using the synthetic lipopeptide MALP-2 as adjuvant

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2003
Stefan Borsutzky
Abstract A major requirement for HIV/AIDS research is the development of a mucosal vaccine that stimulates humoral and cell-mediated immune responses at systemic and mucosal levels, thereby blocking virus replication at the entry port. Thus, a vaccine prototype based on biologically active HIV-1 Tat protein as antigen and the synthetic lipopeptide, macrophage-activating lipopeptide-2 (MALP-2), asa mucosal adjuvant was developed. Intranasal administration to mice stimulated systemic and mucosal anti-Tat antibody responses, and Tat-specific T cell responses, that were more efficient than those observed after i.p. immunization with Tat plus incomplete Freund's adjuvant. Major linear B cell epitopes mapped within aa 1,20 and 46,60, whereas T cell epitopes were identified within aa 36,50 and 56,70. These epitopes have also been described in vaccinated primates and in HIV-1-infected individuals with better prognosis. Analysis of the anti-Tat IgG isotypes in serum, and the cytokine profile of spleen cells indicated that a dominant Th1 helper response was stimulated by Tat plus MALP-2, as opposed to the Th2 response observed with Tat plus incomplete Freund's adjuvant. Tat-specific IFN-,-producing cells were significantly increased only in response to Tat plus MALP-2. These data suggest that Malp-2 may represent an optimal mucosal adjuvant for candidate HIV vaccines based on Tat alone or in combination with other HIV antigens. [source]

Fontolizumab in moderate to severe Crohn's disease: A phase 2, randomized, double-blind, placebo-controlled, multiple-dose study

INFLAMMATORY BOWEL DISEASES, Issue 2 2010
Walter Reinisch MD
Abstract Background: The safety and efficacy of fontolizumab, a humanized anti-interferon gamma antibody, was investigated in patients with Crohn's disease (CD). Elevated gut mucosal levels of interferon gamma, a key cytokine involved in the inflammatory process of CD, are associated with disease symptoms. Methods: A total of 201 patients with Crohn's Disease Activity Index (CDAI) scores between 250 and 450 were randomized to receive an initial intravenous dose of 1.0 or 4.0 mg/kg fontolizumab or placebo, followed by up to 3 subcutaneous doses of 0.1 or 1.0 mg/kg fontolizumab or placebo every 4 weeks. Clinical response at day 29, the primary efficacy endpoint, was defined as a decrease in the CDAI of at least 100 points from baseline levels. Results: Of 201 patients, 135 (67%) completed the study. Day 29 response rates were similar in all treatment groups (31%,38%). At subsequent timepoints a significantly greater proportion of patients in the 1.0 mg/kg intravenous / 1.0 mg/kg subcutaneous fontolizumab group had clinical response and significantly greater improvement in the CDAI score compared with patients who received placebo. All fontolizumab groups had significant improvement in C-reactive protein levels. The overall frequency of adverse events was similar in all groups (58%,75%); most events were related to exacerbation of CD. There was a low frequency (5.2%) of neutralizing antibodies to fontolizumab. Conclusions: Although a strong clinical response to fontolizumab was not observed, significant decreases in C-reactive protein levels suggest a biological effect. Fontolizumab was well tolerated, and further studies to assess its efficacy are warranted. Inflamm Bowel Dis 2009 [source]

Peroxiredoxin I protects gastric mucosa from oxidative injury induced by H. pylori infection

H. pylori selectively blocks EGFR endocytosis via the non-receptor kinase c-Abl and CagA

CELLULAR MICROBIOLOGY, Issue 1 2009
Bianca Bauer
Summary Helicobacter pylori infection is a primary cause of peptic ulcers and is associated with gastric carcinogenesis. The H. pylori -induced pathophysiology may be linked to the deregulation of EGFR signalling. Elevated mucosal levels of EGF and the EGFR have been found in antral gastric biopsies of H. pylori -infected patients. A critical mechanism for regulating EGFR signalling is ligand-induced endocytosis. The internalized receptor recycles back to the plasma membrane for continued signalling or is targeted for degradation terminating receptor signalling. Here, we show that H. pylori blocks EGFR endocytosis and receptor degradation upon prolonged infection of gastric epithelial cells. Moreover, this inhibition occurs via a CagA-dependent, but CagA phosphorylation-independent activation of the non-receptor kinase c-Abl, which in turn phosphorylates the EGFR target site pY1173. This suggests a novel CagA-induced host cell response that is independent of CagA tyrosine phosphorylation. Our data indicate an intriguing strategy of H. pylori in host cell manipulations by altering selective receptor populations via a CagA-dependent endocytic mechanism. Furthermore, we identified a new role for c-Abl in phosphorylation of the EGFR target site pY1173 during H. pylori infection. [source]

Imbalance between interleukin-1 agonists and antagonists: relationship to severity of inflammatory bowel disease

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2004
O. LUDWICZEK
SUMMARY Interleukin (IL)-1 is a key mediator in the pathogenesis of inflammatory bowel disease (IBD). Naturally occurring IL-1 modulators include IL-1 receptor antagonist (IL-1Ra), IL-1 soluble receptor Type I (IL-1sRI), IL-1sRII and IL-1 receptor accessory protein (AcP). Systemic and mucosal levels of IL-1 soluble receptors remain unknown in IBD. Plasma or colonic tissues were obtained from 185 consecutive unselected patients with Crohn's disease (CD) or ulcerative colitis (UC) and from 52 control subjects. Plasma and colonic explant culture supernatants were assessed for IL-1,, IL-1,, IL-1Ra, IL-1sRI and IL-1sRII. Plasma IL-1Ra levels were higher in UC (+93%) than in healthy subjects. IL-1, and IL-1, were not detected. IL-1sRII levels were marginally lower in CD (,10%) and UC (,9%), whereas IL-1sRI levels were elevated in CD (+28%) only. Plasma IL-1sRI levels correlated positively (P < 0·01) with Crohn's disease activity index (r = 0·53), C-reactive protein (r = 0·46) and ,1-acid glycoprotein (r = 0·42). In colonic explant cultures, IL-1, and IL-1Ra levels were elevated in non-lesional (+233% and +185% respectively) and lesional CD (+353% and +1069%), lesional UC (+604% and +1138%), but not in non-lesional UC. IL-1, was elevated in lesional UC (+152%) and CD (+128%). In contrast, IL-1sRII levels were elevated in non-lesional CD (+65%), but remained unchanged in lesional CD, non-lesional and lesional UC. IL-1sRI levels did not differ between patient and control groups. These results indicate that (i) the proinflammatory moiety IL-1sRI is a systemic marker of inflammation and activity in CD and (ii) local shedding of the functional antagonist IL-1sRII may dampen colonic inflammation in CD, but not in UC. [source]