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1.
Article in English | MEDLINE | ID: mdl-30352307

ABSTRACT

Alternagin-C (ALT-C) is a disintegrin-like peptide purified from Rhinocerophis alternatus snake venom with the property of inducing vascular endothelial growth factor (VEGF) expression, endothelial cell proliferation and migration, and angiogenesis. Therefore, this protein could be interesting as a new approach for ischemic heart diseases, an imbalance between myocardial oxygen supply and demand, leading to cardiac dysfunction. We investigated the effects of a single dose of alternagin-C (0.5 mg kg-1, via intra-arterial), after 7 days, on hypoxia/reoxygenation challenge in isolated ventricle strips and on morphological changes and density of blood vessels of the heart, using fish as an alternative experimental model. ALT-C treatment provided protection of cardiomyocytes against hypoxia/reoxygenation-induced negative inotropism. ALT-C also stimulated angiogenesis and improved excitation-contraction coupling during hypoxic conditions. Our results provide a new insight into a functional role of ALT-C against hypoxia/reoxygenation-induced cardiomyocyte injury pointing out to a potential therapeutic strategy for ischemia-related diseases.


Subject(s)
Bothrops , Cardiotonic Agents/therapeutic use , Crotalid Venoms/chemistry , Disease Models, Animal , Disintegrins/therapeutic use , Myocardial Reperfusion Injury/prevention & control , Reptilian Proteins/therapeutic use , Angiogenesis Inducing Agents/administration & dosage , Angiogenesis Inducing Agents/therapeutic use , Animals , Aquaculture , Cardiotonic Agents/administration & dosage , Characiformes , Collagen/metabolism , Coronary Vessels/drug effects , Coronary Vessels/pathology , Coronary Vessels/physiopathology , Disintegrins/administration & dosage , Excitation Contraction Coupling/drug effects , Fish Proteins/metabolism , Heart/drug effects , Heart/physiology , Heart/physiopathology , Injections, Intra-Arterial , Myocardial Contraction/drug effects , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/physiopathology , Myocardium/metabolism , Myocardium/pathology , Neovascularization, Physiologic/drug effects , Reptilian Proteins/administration & dosage
2.
Toxicon ; 110: 1-11, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26615089

ABSTRACT

Alternagin-C (ALT-C) is a disintegrin-like protein purified from the venom of the snake, Rhinocerophis alternatus. Recent studies showed that ALT-C is able to induce vascular endothelial growth factor (VEGF) expression, endothelial cell proliferation and migration, angiogenesis and to increase myoblast viability. This peptide, therefore, can play a crucial role in tissue regeneration mechanisms. The aim of this study was to evaluate the effects of a single dose of alternagin-C (0.5 mg kg(-1), via intra-arterial) on in vitro cardiac function of the freshwater fish traíra, Hoplias malabaricus, after 7 days. ALT-C treatment increased the cardiac performance promoting: 1) significant increases in the contraction force and in the rates of contraction and relaxation with concomitant decreases in the values of time to the peak tension and time to half- and 90% relaxation; 2) improvement in the cardiac pumping capacity and maximal electrical stimulation frequency, shifting the optimum frequency curve upward and to the right; 3) increases in myocardial VEGF levels and expression of key Ca(2+)-cycling proteins such as SERCA (sarcoplasmic reticulum Ca(2+)-ATPase), PLB (phospholamban), and NCX (Na(+)/Ca(2+) exchanger); 4) abolishment of the typical negative force-frequency relationship of fish myocardium. In conclusion, this study indicates that ALT-C improves cardiac function, by increasing Ca(2+) handling efficiency leading to a positive inotropism and chronotropism. The results suggest that ALT-C may lead to better cardiac output regulation indicating its potential application in therapies for cardiac contractile dysfunction.


Subject(s)
Bothrops , Cardiotonic Agents/pharmacology , Disintegrins/pharmacology , Heart Rate/drug effects , Heart Ventricles/drug effects , Myocardial Contraction/drug effects , Reptilian Proteins/pharmacology , Animals , Aquaculture , Calcium-Binding Proteins/agonists , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/isolation & purification , Characiformes , Crotalid Venoms/chemistry , Disintegrins/administration & dosage , Disintegrins/isolation & purification , Fish Proteins/agonists , Fish Proteins/genetics , Fish Proteins/metabolism , Gene Expression Regulation/drug effects , Heart Ventricles/enzymology , Heart Ventricles/metabolism , Injections, Intra-Arterial , Random Allocation , Reptilian Proteins/administration & dosage , Reptilian Proteins/isolation & purification , Sarcoplasmic Reticulum Calcium-Transporting ATPases/chemistry , Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Sodium-Calcium Exchanger/agonists , Sodium-Calcium Exchanger/genetics , Sodium-Calcium Exchanger/metabolism , Vascular Endothelial Growth Factor A/agonists , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Ventricular Function/drug effects
3.
Braz. j. microbiol ; 44(4): 1207-1214, Oct.-Dec. 2013. ilus, tab
Article in English | LILACS | ID: lil-705249

ABSTRACT

Fungi have been recently recognized as organisms able to grow in presence of high salt concentration with halophilic and halotolerance properties and their ligninolytic enzyme complex have an unspecific action enabling their use to degradation of a number of xenobiotic compounds. In this work, both the effect of salt and polyols on growth of the basidiomycetes strains, on their ability to produce ligninolytic enzyme and diuron degradation were evaluated. Results showed that the presence of NaCl in the culture medium affected fungal specimens in different ways. Seven out of ten tested strains had growth inhibited by salt while Dacryopinax elegans SXS323, Polyporus sp MCA128 and Datronia stereoides MCA167 fungi exhibited higher biomass production in medium containing 0.5 and 0.6 mol.L-1 of NaCl, suggesting to be halotolerant. Polyols such as glycerol and mannitol added into the culture media improved the biomass and ligninases production by D. elegans but the fungus did not reveal consumption of these polyols from media. This fungus degraded diuron in medium control, in presence of NaCl as well as polyols, produced MnP, LiP and laccase.


Subject(s)
Basidiomycota/enzymology , Basidiomycota/metabolism , Herbicides/metabolism , Oxygenases/metabolism , Sodium Chloride/metabolism , Biomass , Biotransformation , Basidiomycota/drug effects , Basidiomycota/growth & development , Culture Media/chemistry , Diuron/metabolism , Growth Inhibitors/metabolism , Growth Inhibitors/toxicity , Polymers/metabolism , Polymers/toxicity , Sodium Chloride/toxicity
4.
Braz J Microbiol ; 44(4): 1207-14, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24688513

ABSTRACT

Fungi have been recently recognized as organisms able to grow in presence of high salt concentration with halophilic and halotolerance properties and their ligninolytic enzyme complex have an unspecific action enabling their use to degradation of a number of xenobiotic compounds. In this work, both the effect of salt and polyols on growth of the basidiomycetes strains, on their ability to produce ligninolytic enzyme and diuron degradation were evaluated. Results showed that the presence of NaCl in the culture medium affected fungal specimens in different ways. Seven out of ten tested strains had growth inhibited by salt while Dacryopinax elegans SXS323, Polyporus sp MCA128 and Datronia stereoides MCA167 fungi exhibited higher biomass production in medium containing 0.5 and 0.6 mol.L(-1) of NaCl, suggesting to be halotolerant. Polyols such as glycerol and mannitol added into the culture media improved the biomass and ligninases production by D. elegans but the fungus did not reveal consumption of these polyols from media. This fungus degraded diuron in medium control, in presence of NaCl as well as polyols, produced MnP, LiP and laccase.


Subject(s)
Basidiomycota/enzymology , Basidiomycota/metabolism , Herbicides/metabolism , Oxygenases/metabolism , Sodium Chloride/metabolism , Basidiomycota/drug effects , Basidiomycota/growth & development , Biomass , Biotransformation , Culture Media/chemistry , Diuron/metabolism , Growth Inhibitors/metabolism , Growth Inhibitors/toxicity , Polymers/metabolism , Polymers/toxicity , Sodium Chloride/toxicity
5.
J Clin Pathol ; 60(1): 82-4, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17213350

ABSTRACT

INTRODUCTION: Cellular blue naevi (CBN) measure 1-2 cm in diameter and affect the dermis, occasionally extending into the subcutaneous fat. The case of a 14-year-old boy with a giant CBN (GCBN) involving the right half of the face, the jugal mucosa and the lower eyelid with a tumour that had infiltrated the bone and the maxillary and ethmoidal sinuses is reported. METHODS: Biopsies were taken from the skin, jugal mucosa and maxillary sinus. The following markers were used in the immunohistochemical evaluation: CD34, CD56, HMB-45, anti-S100, A-103, Melan A and MIB-1. RESULTS: The biopsy specimens showed a biphasic pattern affecting the lower dermis, subcutaneous fat, skeletal muscle, bone, jugal mucosa and maxillary sinus, but there was no histological evidence of malignancy. The tumour cells were CD34-, CD56-, HMB45+, anti-S100+ and A-103+. Melan A was focally expressed. No positive MIB-1 cells were identified. DISCUSSION: The present case shows that GCBN may infiltrate deeply, with no evidence of malignancy.


Subject(s)
Facial Neoplasms/pathology , Nevus, Blue/pathology , Skin Neoplasms/pathology , Adolescent , Biomarkers, Tumor/metabolism , Biopsy , Facial Neoplasms/diagnostic imaging , Humans , Male , Nevus, Blue/diagnostic imaging , Skin Neoplasms/diagnostic imaging , Tomography, X-Ray Computed
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