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1.
Mucosal Immunol ; 9(2): 322-35, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26174763

ABSTRACT

Intestinal helminth parasites are potent inducers of T helper type 2 (Th2) response and have a regulatory role, notably on intestinal inflammation. As infection with schistosomes is unlikely to provide a reliable treatment of inflammatory bowel diseases, we have investigated the beneficial effect of a schistosome enzymatic protein, the 28-kDa glutathione S-transferase (P28GST), on the modulation of disease activity and immune responses in experimental colitis. Our results showed that immunization with recombinant P28GST is at least as efficient as established schistosome infection to reduce colitis lesions and expression of pro-inflammatory cytokines. Considering underlying mechanisms, the decrease of inflammatory parameters was associated with the polarization of the immune system toward a Th2 profile, with local and systemic increases of interleukin (IL)-13 and IL-5. Dense eosinophil infiltration was observed in the colons of P28GST-immunized rats and mice. Depletion of eosinophils by treatment with an anti-Siglec-F monoclonal antibody and use of IL-5-deficient mice led to the loss of therapeutic effect, suggesting the crucial role for eosinophils in colitis prevention by P28GST. These findings reveal that immunization with P28GST, a unique recombinant schistosome enzyme, ameliorates intestinal inflammation through eosinophil-dependent modulation of harmful type 1 responses, representing a new immuno-regulatory strategy against inflammatory bowel diseases.


Subject(s)
Colitis/prevention & control , Colon/immunology , Eosinophils/immunology , Glutathione Transferase/immunology , Helminth Proteins/immunology , Schistosomiasis mansoni/immunology , Th2 Cells/immunology , Animals , Antibodies, Monoclonal/pharmacology , Antigens, Differentiation, Myelomonocytic , Cell Movement , Colitis/chemically induced , Colitis/immunology , Colitis/pathology , Colon/parasitology , Colon/pathology , Disease Models, Animal , Eosinophils/parasitology , Eosinophils/pathology , Female , Glutathione Transferase/administration & dosage , Glutathione Transferase/chemistry , Helminth Proteins/administration & dosage , Helminth Proteins/chemistry , Immunization , Interleukin-13/biosynthesis , Interleukin-13/immunology , Interleukin-5/biosynthesis , Interleukin-5/deficiency , Interleukin-5/immunology , Intestinal Mucosa/immunology , Intestinal Mucosa/parasitology , Intestinal Mucosa/pathology , Male , Mice , Mice, Inbred BALB C , Rats , Rats, Sprague-Dawley , Recombinant Proteins/administration & dosage , Recombinant Proteins/chemistry , Recombinant Proteins/immunology , Schistosoma mansoni/chemistry , Schistosoma mansoni/immunology , Schistosomiasis mansoni/parasitology , Sialic Acid Binding Immunoglobulin-like Lectins , Th1 Cells/immunology , Th1 Cells/parasitology , Th1 Cells/pathology , Th2 Cells/parasitology , Th2 Cells/pathology , Trinitrobenzenesulfonic Acid
2.
Acta Biol Hung ; 64(3): 305-18, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24013892

ABSTRACT

Fasciated and normal stem segments of Opuntia microdasys, Opuntia cylindrica, Huernia primulina and Euphorbia lactea were collected from the same plant and compared for their anatomy, water relations and genetic variations. Anatomical differences in terms of thickness of cuticle, vascular bundle, xylem and phloem were analyzed in both normal and fasciated stems. The mucilage cells were higher in the fasciated form of Opuntia microdasys than that in the normal form. Water status in terms of total water content (TWC), water deficit and relative water content (RWC) was influenced by fasciation. Genetic variations were tested in normal and fasciated stems using randomly amplified polymorphic DNA (RAPD) fingerprints and SDS-PAGE of soluble protein extracts. SDS-PAGE protein and RAPD analysis confirmed that normal and fasciated tissues were genetically different. Polymerase chain reaction (PCR) yielded different polymorphic banding patterns that were unique to each primer and distinguishable over all samples. The PCR results of normal and fasciated samples were significantly different in cases of primers P1, P2 and P3. These results indicate that occurrence of fasciation in Opuntia microdasys, Opuntia cylindrica, Huernia primulina and Euphorbia lactea is an epigenetic mutation of tissues.


Subject(s)
Euphorbia/anatomy & histology , Opuntia/anatomy & histology , Plant Proteins/metabolism , Plant Stems/anatomy & histology , Water/physiology , Euphorbia/genetics , Euphorbia/metabolism , Opuntia/genetics , Opuntia/metabolism , Plant Proteins/genetics , Plant Stems/genetics , Polymerase Chain Reaction , Random Amplified Polymorphic DNA Technique
3.
J Viral Hepat ; 16(7): 500-5, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19457138

ABSTRACT

The most reliable predictor of a sustained virological response in patients with persistently normal ALT has not been identified. We analysed 17 patients with genotype 1 chronic HCV who underwent therapy with pegylated interferon alfa 2b and ribavirin for 48 weeks. Two patients discontinued therapy within 28 days because of side effects and the remaining 15 patients were analysed in detail. An analysis of on treatment virological response using area under the receiver operating characteristic analyses showed that a 2 log drop in HCV RNA at day 28 was the best predictor of a sustained virological response and a failure to reduce viral load by 2 logs correctly identified patients with a low (<15%) probability of achieving a sustained virological response. Introduction of this early discontinuation rule in patients with normal ALT would allow nearly half of the patients to discontinue futile therapy at an early stage.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/isolation & purification , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Viral Load , Adult , Alanine Transaminase/blood , Female , Humans , Interferon alpha-2 , Interferon-alpha/therapeutic use , Male , Polyethylene Glycols/therapeutic use , Prognosis , Prospective Studies , Recombinant Proteins , Ribavirin/therapeutic use , Treatment Outcome
4.
Pathol Biol (Paris) ; 57(1): 101-6, 2009 Feb.
Article in French | MEDLINE | ID: mdl-18842356

ABSTRACT

AIM OF THE WORK: We have researched and identified Herpes viruses on the esophageal biopsies taken during the period between September 2006 and March 2008 for 15 suspected patients. PATIENTS AND METHODS: The esophageal biopsies were transferred to the laboratory being conserved in physiological serum and frozen at -80 degrees C for PCR. A fragment was conserved for histopathological analysis. The specimen was defrozen and refrozen in liquid azote (to limit the inhibitors) and crushed to the powder form. Extraction was then done following the prerecognised protocol (Herpès Consensus Générique-"Argene"). That kit allows the amplification consensus of the viral genome of the most frequently encountered Herpes family virus: HSV1, HSV2, CMV, VZV, EBV and HHV6. The identification of the implicated virus was done by the Hybridowell Herpes Identification (Argene) kit in parallel with the migration of SDS gel of the obtained amplifications. RESULTS: HSV1 was identified in seven esophageal biopsies between the 15 studied. HHV6 and the association HHV6/EBV for two patients and only one biopsy had inconclusive. The endoscopy and the histopathological examination had confirmed ulcerated esophagitis with cytopathogene aspect in favour of viral infection for six patients. CONCLUSION: In absence of inhibitors, the adaptation of the extraction technique of the fragments of tissue for few millimetres and the amplifications by PCR had allowed rapid confirmation of the diagnosis of herpetic esophagitis secondary to HSV1 even before the results of the histopathological examination. Treatment by acyclovir entrained regression of the disease.


Subject(s)
Esophagitis/diagnosis , Herpes Simplex/diagnosis , Herpesvirus 1, Human/isolation & purification , Polymerase Chain Reaction/methods , Biopsy , Comorbidity , DNA, Viral/isolation & purification , Electrophoresis, Agar Gel , Esophagitis/virology , Esophagoscopy , Herpes Simplex/virology , Herpesvirus 1, Human/genetics , Humans , Immunocompetence , Reagent Kits, Diagnostic , Specimen Handling , Ulcer/virology
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