Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Database
Type of study
Language
Publication year range
1.
Vet Res Forum ; 7(3): 267-270, 2016.
Article in English | MEDLINE | ID: mdl-27872725

ABSTRACT

Caudal duplication (dipygus) is an uncommon pathologic of conjoined twinning. The conjoined malformation is classified according to the nature and site of the union. We report the presence of this malformation in a female crossbreed puppy. The puppy was delivered by caesarean section following a prolonged period of dystocia. External findings showed a single head (monocephalus) and a normal cranium with no fissure in the medial line detected. The thorax displayed a caudal duplication arising from the lumbosacral region (rachipagus). The puppy had three upper limbs, a right and left, and a third limb in the dorsal region where the bifurcation began. The subsequent caudal duplication appeared symmetrical. Necropsy revealed internal abnormalities consisting of a complete duplication of the urogenital system and a duplication of the large intestines arising from a bifurcation of the caudal ileum . Considering the morphophysiological description the malformation described would be classified as the first case in the dog of a monocephalusrachipagustribrachius tetrapus.

2.
Free Radic Biol Med ; 89: 557-66, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26454078

ABSTRACT

Atherogenesis is associated with the early retention of low-density lipoproteins (LDL) in the arterial intima by interaction with glycosaminoglycan (GAG)-side chains of proteoglycans. Retained LDL undergo reactive oxygen species-mediated oxidation. Oxidized LDL trigger oxidative stress (OS) and inflammation, contributing to atherosclerosis development. Recently, we reported the preventive anti-atherogenic properties of the chimeric mouse/human monoclonal antibody (mAb) chP3R99-LALA, which were related to the induction of anti-chondroitin sulfate antibody response able to inhibit chondroitin sulfate dependent LDL-enhanced oxidation. In the present work, we aimed at further investigating the impact of chP3R99-LALA mAb vaccination on progressive atherosclerosis in apolipoprotein E-deficient mice (apoE(-/-)) fed with a high-fat high-cholesterol diet receiving 5 doses (50 µg) of the antibody subcutaneously, when ~5% of the aortic area was covered by lesions. Therapeutic immunization with chP3R99-LALA mAb halted atherosclerotic lesions progression. In addition, aortic OS was modulated, as shown by a significant (p<0.05) reduction of lipid and protein oxidation, preservation of antioxidant enzymes activity and reduced glutathione, together with a decrease of nitric oxide levels. chP3R99-LALA mAb immunization also regulated aortic NF-κB activation, diminishing the proinflammatory IL1-ß and TNF-α gene expression as well as the infiltration of macrophages into the arterial wall. The therapeutic immunization of apoE(-/-) with progressive atheromas and persistent hypercholesterolemia using chP3R99-LALA mAb arrested further development of lesions, accompanied by a decrease of aortic OS and NF-κB-regulated pro-inflammatory cytokine gene expression. These results contribute to broaden the potential use of this anti-GAG antibody-based immunotherapy as a novel approach to target atherosclerosis at different phases of progression.


Subject(s)
Antibodies, Monoclonal/pharmacology , Atherosclerosis/pathology , Chondroitin Sulfates/antagonists & inhibitors , Glycosaminoglycans/antagonists & inhibitors , Vaccination/methods , Animals , Apolipoproteins E/deficiency , Chondroitin Sulfates/immunology , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Glycosaminoglycans/immunology , Humans , Immunohistochemistry , Male , Mice , Mice, Knockout , Oxidation-Reduction , Polymerase Chain Reaction , Recombinant Fusion Proteins/immunology
3.
MAbs ; 6(5): 1340-6, 2014.
Article in English | MEDLINE | ID: mdl-25517318

ABSTRACT

The progression of atherosclerosis is favored by increasing amounts of chondroitin sulfate proteoglycans in the artery wall. We previously reported the reactivity of chP3R99 monoclonal antibody (mAb) with sulfated glycosaminoglycans and its association with the anti-atherogenic properties displayed. Now, we evaluated the accumulation of this mAb in atherosclerotic lesions and its potential use as a probe for specific in vivo detection of the disease. Atherosclerosis was induced in NZW rabbits (n = 14) by the administration of Lipofundin 20% using PBS-receiving animals as control (n = 8). Accumulation of chP3R99 mAb in atherosclerotic lesions was assessed either by immunofluorescence detection of human IgG in fresh-frozen sections of aorta, or by immunoscintigraphy followed by biodistribution of the radiotracer upon administration of (99m)Tc-chP3R99 mAb. Immunofluorescence studies revealed the presence of chP3R99 mAb in atherosclerotic lesions 24 h after intravenous administration, whereas planar images showed an evident accumulation of (99m)Tc-chP3R99 mAb in atherosclerotic rabbit carotids. Accordingly, (99m)Tc-chP3R99 mAb uptake by lesioned aortic arch and thoracic segment was increased 5.6-fold over controls and it was 3.9-folds higher in carotids, in agreement with immunoscintigrams. Moreover, the deposition of (99m)Tc-chP3R99 mAb in the artery wall was associated both with the presence and size of the lesions in the different portions of evaluated arteries and was greater than in non-targeted organs. In conclusion, chP3R99 mAb preferentially accumulates in arterial atherosclerotic lesions supporting the potential use of this anti-glycosaminoglycans antibody for diagnosis and treatment of atherosclerosis.


Subject(s)
Antibodies, Monoclonal/pharmacology , Atherosclerosis/drug therapy , Glycosaminoglycans/antagonists & inhibitors , Recombinant Fusion Proteins/pharmacology , Administration, Intravenous , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/pharmacokinetics , Aorta/drug effects , Aorta/metabolism , Aorta/pathology , Atherosclerosis/chemically induced , Atherosclerosis/metabolism , Drug Combinations , Fluorescent Antibody Technique , Glycosaminoglycans/metabolism , Humans , Male , Mice , Organotechnetium Compounds , Phospholipids , Rabbits , Radioimmunodetection/methods , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/pharmacokinetics , Sorbitol , Sulfates/metabolism , Technetium , Time Factors , Tissue Distribution
4.
Arterioscler Thromb Vasc Biol ; 32(12): 2847-54, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23087361

ABSTRACT

OBJECTIVE: The pathogenesis of atherosclerosis is associated with the early retention of low-density lipoproteins that are trapped in the extracellular matrix of the arterial intima by interaction with glycosaminoglycan side chains of proteoglycans. Mutant mouse/human chimeric antibodies of the murine monoclonal antibody P3, which react with N-glycolyl-containing gangliosides and sulfated glycosaminoglycans, were tested for their potentially antiatherogenic properties through the induction of an idiotypic antibody network that may specifically interfere with the binding of low-density lipoproteins to proteoglycan side chains, low-density lipoprotein modification, and foam cell formation. METHODS AND RESULTS: Apolipoprotein E-deficient mice fed a high-fat, high-cholesterol diet received 5 to 6 doses of chP3R99 or chP3S98 mutant antibodies, showing high and low reactivity, respectively, against their respective antigens. Both chimeric antibodies elicited an immunodominant anti-idiotypic response in the absence of adjuvant. A striking (40%-43%) reduction (P<0.01) in total lesion areas was observed in 18-week-old mice immunized with chP3R99, but not chP3S98, compared with PBS-treated mice. The antiatherosclerotic effect was associated with increased mice sera reactivity against heparin and sulfated glycosaminoglycans, including chondroitin and dermatan sulfate. In addition, purified IgG from chP3R99-immunized mice blocked the retention of apolipoprotein B-containing lipoproteins within the arterial wall of apolipoprotein E(-/-) mice. CONCLUSIONS: The present study supports use of active immunization and the mounting of an idiotypic antibody network response against glycosaminoglycans as a novel approach to target atherosclerosis.


Subject(s)
Antibodies, Anti-Idiotypic/therapeutic use , Apolipoproteins E/deficiency , Atherosclerosis/prevention & control , Glycosaminoglycans/immunology , Glycosaminoglycans/metabolism , Sulfates/metabolism , Animals , Antibodies, Anti-Idiotypic/immunology , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Arteries/metabolism , Atherosclerosis/etiology , Atherosclerosis/metabolism , Cholesterol, Dietary/adverse effects , Diet, High-Fat/adverse effects , Disease Models, Animal , Humans , Lipoproteins, LDL/metabolism , Male , Mice , Mice, Knockout , Mutant Chimeric Proteins/immunology , Mutant Chimeric Proteins/therapeutic use
5.
Arterioscler Thromb Vasc Biol ; 32(3): 595-604, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22267481

ABSTRACT

OBJECTIVE: Subendothelial retention of proatherogenic lipoproteins by proteoglycans is critical in atherosclerosis. The aim of this study was to characterize the recognition and antiatherogenic properties of a chimeric monoclonal antibody (mAb) that reacts with sulfated molecules. METHODS AND RESULTS: chP3R99 mAb recognized sulfated glycosaminoglycans, mainly chondroitin sulfate (CS), by ELISA. This mAb blocked ≈70% of low-density lipoprotein (LDL)-CS association and ≈80% of LDL oxidation in vitro, and when intravenously injected to Sprague-Dawley rats (n=6, 1 mg/animal), it inhibited LDL (4 mg/kg intraperitoneally, 1 hour later) retention and oxidation in the artery wall. Moreover, subcutaneous immunization of New Zealand White rabbits (n=19) with chP3R99 mAb (100 µg, 3 doses at weekly intervals) prevented Lipofundin-induced atherosclerosis (2 mL/kg, 8 days) with a 22-fold reduction in the intima-media ratio (P<0.01). Histopathologic and ultrastructural studies showed no intimal alterations or slight thickening, with preserved junctions between endothelial cells and scarce collagen fibers and glycosaminoglycans. In addition, immunization with chP3R99 mAb suppressed macrophage infiltration in aorta and preserved redox status. The atheroprotective effect was associated with the induction of anti-CS antibodies in chP3R99-immunized rabbits, capable of blocking CS-LDL binding and LDL oxidation. CONCLUSION: These results support the use of anti-sulfated glycosaminoglycan antibody-based immunotherapy as a potential tool to prevent atherosclerosis.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Atherosclerosis/prevention & control , Chondroitin Sulfates/antagonists & inhibitors , Glycosaminoglycans/antagonists & inhibitors , Immunization , Animals , Antibody Specificity , Atherosclerosis/chemically induced , Atherosclerosis/immunology , Atherosclerosis/metabolism , Atherosclerosis/pathology , Biological Transport , Cell Line , Chondroitin Sulfates/immunology , Disease Models, Animal , Drug Combinations , Enzyme-Linked Immunosorbent Assay , Foam Cells/immunology , Foam Cells/metabolism , Glycosaminoglycans/immunology , Lipoproteins, LDL/metabolism , Mice , Oxidation-Reduction , Oxidative Stress , Phospholipids , Rabbits , Rats , Rats, Sprague-Dawley , Sorbitol
SELECTION OF CITATIONS
SEARCH DETAIL
...