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Eiji Miyoshi - One of the best experts on this subject based on the ideXlab platform.
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identification of an inducible factor secreted by pancreatic cancer cell lines that stimulates the production of fucosylated Haptoglobin in hepatoma cells
Biochemical and Biophysical Research Communications, 2008Co-Authors: Megumi Narisada, Tsutomu Nakagawa, Kenta Moriwaki, Sayuri Kawamoto, Kana Kuwamoto, Hitoshi Matsumoto, Michio Asahi, Nobuto Koyama, Eiji MiyoshiAbstract:Summary Fucosylation is one of the most important oligosaccharide modifications and is involved in cancer and inflammation. Recently, fucosylated Haptoglobin was identified as a possible tumor marker for pancreatic cancer. The molecular mechanism underlying increases in fucosylated Haptoglobin in sera of patients with pancreatic cancer seems to be complicated. Our previous study [N. Okuyama, Y. Ide, M. Nakano, T. Nakagawa, K. Yamanaka, K. Moriwaki, K. Murata, H. Ohigashi, S. Yokoyama, H. Eguchi, O. Ishikawa, T. Ito, M. Kato, A. Kasahara, S. Kawano, J. Gu, N. Taniguchi, E. Miyoshi, Fucosylated Haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation, Int. J. Cancer 118 (11) (2006) 2803–2808] demonstrated that pancreatic cancer cells secrete a factor, which induces the production of Haptoglobin in hepatoma cells. In the present study, we found that interleukin 6 (IL6) expressed in pancreatic cancer is a factor that induces the Haptoglobin production, using a neutralizing antibody for IL6. Real-time PCR analyses revealed the up-regulation of fucosylation regulatory genes after IL6 treatment, resulting increases in fucosylated Haptoglobin being revealed by a lectin ELISA. This pathway could be one of the possible mechanisms underlying increases in Haptoglobin in sera of patients with pancreatic cancer.
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site specific analysis of n glycans on Haptoglobin in sera of patients with pancreatic cancer a novel approach for the development of tumor markers
International Journal of Cancer, 2008Co-Authors: Miyako Nakano, Tsutomu Nakagawa, Toshifumi Ito, Takatoshi Kitada, Taizo Hijioka, Akinori Kasahara, Michiko Tajiri, Yoshinao Wada, Naoyuki Taniguchi, Eiji MiyoshiAbstract:It was found in our previous studies that the concentration of fucosylated Haptoglobin had increased in the sera of patients with pancreatic cancer (PC) compared to those of other types of cancer and normal controls. Haptoglobin, an acute phase protein, has four potential N-glycosylation sites, although it remains unknown which site is responsible for the change in fucosylated N-glycans. In the present study, site-specific N-glycan structures of Haptoglobin in sera obtained from patients with PC or chronic pancreatitis (CP) were analyzed using liquid chromatography-electrospray ionization mass spectrometry. Mass spectrometry analyses demonstrated that concentrations of total fucosylated di-, tri- and tetra-branched glycans of Haptoglobin increased in the sera of PC patients. Tri-antennary N-glycans containing a Lewis X-type fucose markedly increased at the Asn211 site of Haptoglobin N-glycans. While fucosylated N-glycans derived from serum Haptoglobin of patients with CP slightly increased, di-fucosylated tetra-antennary N-glycans were observed only at this site in PC patients, and were absent in the Haptoglobin of normal controls and individuals with CP. Thus, the present study provides evidence that site-specific analyses of N-glycans may be useful as novel tumor markers for PC.
Nathan Brinkman - One of the best experts on this subject based on the ideXlab platform.
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Haptoglobin and hemopexin inhibit vaso occlusion and inflammation in murine sickle cell disease role of heme oxygenase 1 induction
PLOS ONE, 2018Co-Authors: John D Belcher, Chunsheng Chen, Julia Nguyen, Fuad Abdulla, Ping Zhang, Hao Nguyen, Phong Nguyen, Trevor Killeen, Sylvia Miescher, Nathan BrinkmanAbstract:During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. Plasma Haptoglobin and hemopexin scavenge free hemoglobin and heme, respectively, but can be depleted in hemolytic states. Haptoglobin and hemopexin supplementation protect tissues, including the vasculature, liver and kidneys. It is widely assumed that these protective effects are due primarily to hemoglobin and heme clearance from the vasculature. However, this simple assumption does not account for the consequent cytoprotective adaptation seen in cells and organs. To further address the mechanism, we used a hyperhemolytic murine model (Townes-SS) of sickle cell disease to examine cellular responses to Haptoglobin and hemopexin supplementation. A single infusion of Haptoglobin or hemopexin (± equimolar hemoglobin) in SS-mice increased heme oxygenase-1 (HO-1) in the liver, kidney and skin several fold within 1 hour and decreased nuclear NF-ĸB phospho-p65, and vaso-occlusion for 48 hours after infusion. Plasma hemoglobin and heme levels were not significantly changed 1 hour after infusion of Haptoglobin or hemopexin. Haptoglobin and hemopexin also inhibited hypoxia/reoxygenation and lipopolysaccharide-induced vaso-occlusion in SS-mice. Inhibition of HO-1 activity with tin protoporphyrin blocked the protections afforded by Haptoglobin and hemopexin in SS-mice. The HO-1 reaction product carbon monoxide, fully restored the protection, in part by inhibiting Weibel-Palade body mobilization of P-selectin and von Willebrand factor to endothelial cell surfaces. Thus, the mechanism by which Haptoglobin and hemopexin supplementation in hyperhemolytic SS-mice induces cytoprotective cellular responses is linked to increased HO-1 activity.
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Haptoglobin and hemopexin infusion efficiently activates the nrf2 ho 1 axis and inhibits inflammation and vaso occlusion in murine sickle cell disease
Blood, 2016Co-Authors: John D Belcher, Nathan Brinkman, Chunsheng Chen, Julia Nguyen, Fuad Abdulla, Ping Zhang, Hao Nguyen, Phong Nguyen, Gregory M VercellottiAbstract:Free hemoglobin and hemin, released by red blood cells during intravascular hemolysis, promote vasculopathy, inflammation, thrombosis, and renal injury. Plasma Haptoglobin and hemopexin tightly bind free hemoglobin and hemin, respectively, thwarting these clinical sequelae. In sickle cell disease (SCD), chronic hemolysis can deplete plasma Haptoglobin and hemopexin in humans and mice. To explore mechanisms mediating this protection and provide a basis for supplementation in SCD patients, dorsal skin fold chambers were implanted onto Townes-SS mice and microvascular stasis (% non-flowing venules) was measured in response to a hemoglobin challenge. Human Haptoglobin, hemopexin, or albumin was co-infused with hemoglobin or 1 hour after hemoglobin at equimolar concentrations. Sickle mice co-infused with hemoglobin/Haptoglobin, hemoglobin/hemopexin or hemoglobin/Haptoglobin/hemopexin had less stasis 1 to 4 hours after infusion, compared to albumin- and saline-treated mice (*p Disclosures Belcher:CSL-Behring: Research Funding; Imara: Research Funding. Chen:Imara: Research Funding. Brinkman:CSL-Behring: Employment. Vercellotti:CSL-Behring: Research Funding; Imara: Research Funding.
Tsutomu Nakagawa - One of the best experts on this subject based on the ideXlab platform.
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identification of an inducible factor secreted by pancreatic cancer cell lines that stimulates the production of fucosylated Haptoglobin in hepatoma cells
Biochemical and Biophysical Research Communications, 2008Co-Authors: Megumi Narisada, Tsutomu Nakagawa, Kenta Moriwaki, Sayuri Kawamoto, Kana Kuwamoto, Hitoshi Matsumoto, Michio Asahi, Nobuto Koyama, Eiji MiyoshiAbstract:Summary Fucosylation is one of the most important oligosaccharide modifications and is involved in cancer and inflammation. Recently, fucosylated Haptoglobin was identified as a possible tumor marker for pancreatic cancer. The molecular mechanism underlying increases in fucosylated Haptoglobin in sera of patients with pancreatic cancer seems to be complicated. Our previous study [N. Okuyama, Y. Ide, M. Nakano, T. Nakagawa, K. Yamanaka, K. Moriwaki, K. Murata, H. Ohigashi, S. Yokoyama, H. Eguchi, O. Ishikawa, T. Ito, M. Kato, A. Kasahara, S. Kawano, J. Gu, N. Taniguchi, E. Miyoshi, Fucosylated Haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation, Int. J. Cancer 118 (11) (2006) 2803–2808] demonstrated that pancreatic cancer cells secrete a factor, which induces the production of Haptoglobin in hepatoma cells. In the present study, we found that interleukin 6 (IL6) expressed in pancreatic cancer is a factor that induces the Haptoglobin production, using a neutralizing antibody for IL6. Real-time PCR analyses revealed the up-regulation of fucosylation regulatory genes after IL6 treatment, resulting increases in fucosylated Haptoglobin being revealed by a lectin ELISA. This pathway could be one of the possible mechanisms underlying increases in Haptoglobin in sera of patients with pancreatic cancer.
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site specific analysis of n glycans on Haptoglobin in sera of patients with pancreatic cancer a novel approach for the development of tumor markers
International Journal of Cancer, 2008Co-Authors: Miyako Nakano, Tsutomu Nakagawa, Toshifumi Ito, Takatoshi Kitada, Taizo Hijioka, Akinori Kasahara, Michiko Tajiri, Yoshinao Wada, Naoyuki Taniguchi, Eiji MiyoshiAbstract:It was found in our previous studies that the concentration of fucosylated Haptoglobin had increased in the sera of patients with pancreatic cancer (PC) compared to those of other types of cancer and normal controls. Haptoglobin, an acute phase protein, has four potential N-glycosylation sites, although it remains unknown which site is responsible for the change in fucosylated N-glycans. In the present study, site-specific N-glycan structures of Haptoglobin in sera obtained from patients with PC or chronic pancreatitis (CP) were analyzed using liquid chromatography-electrospray ionization mass spectrometry. Mass spectrometry analyses demonstrated that concentrations of total fucosylated di-, tri- and tetra-branched glycans of Haptoglobin increased in the sera of PC patients. Tri-antennary N-glycans containing a Lewis X-type fucose markedly increased at the Asn211 site of Haptoglobin N-glycans. While fucosylated N-glycans derived from serum Haptoglobin of patients with CP slightly increased, di-fucosylated tetra-antennary N-glycans were observed only at this site in PC patients, and were absent in the Haptoglobin of normal controls and individuals with CP. Thus, the present study provides evidence that site-specific analyses of N-glycans may be useful as novel tumor markers for PC.
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fucosylated Haptoglobin is a novel marker for pancreatic cancer a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation
International Journal of Cancer, 2006Co-Authors: Noriko Okuyama, Yoshihito Ide, Miyako Nakano, Tsutomu Nakagawa, Kanako Yamanaka, Kenta Moriwaki, Kohei Murata, Hiroaki Ohigashi, Shigekazu Yokoyama, Hidetoshi EguchiAbstract:Changes in oligosaccharide structures have been reported in certain types of malignant transformations and, thus, could be used for tumor markers in certain types of cancer. In the case of pancreatic cancer cell lines, a variety of fucosylated proteins are secreted into their conditioned media. To identify fucosylated proteins in the serum of patients with pancreatic cancer, we performed western blot analyses using Aleuria Aurantica Lectin (AAL), which is specific for fucosylated structures. An approximately 40 kD protein was found to be highly fucosylated in pancreatic cancer and an N-terminal analysis revealed that it was the beta chain of Haptoglobin. While the appearance of fucosylated Haptoglobin has been reported in other diseases such as hepatocellular carcinoma, liver cirrhosis, gastric cancer and colon cancer, the incidence was significantly higher in the case of pancreatic cancer. Fucosylated Haptoglobin was observed more frequently at the advanced stage of pancreatic cancer and disappeared after an operation. A mass spectrometry analysis of Haptoglobin purified from the serum of patients with pancreatic cancer and the medium from a pancreatic cancer cell line, PSN-1, showed that the alpha 1-3/alpha 1-4/alpha 1-6 fucosylation of Haptoglobin was increased in pancreatic cancer. When a hepatoma cell line, Hep3B, was cultured with the conditioned media from pancreatic cancer cells, Haptoglobin secretion was dramatically increased. These findings suggest that fucosylated Haptoglobin could serve as a novel marker for pancreatic cancer. Two possibilities were considered in terms of the fucosylation of Haptoglobin. One is that pancreatic cancer cells, themselves, produce fucosylated Haptoglobin; the other is that pancreatic cancer produces a factor, which induces the production of fucosylated Haptoglobin in the liver.
John D Belcher - One of the best experts on this subject based on the ideXlab platform.
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Haptoglobin and hemopexin inhibit vaso occlusion and inflammation in murine sickle cell disease role of heme oxygenase 1 induction
PLOS ONE, 2018Co-Authors: John D Belcher, Chunsheng Chen, Julia Nguyen, Fuad Abdulla, Ping Zhang, Hao Nguyen, Phong Nguyen, Trevor Killeen, Sylvia Miescher, Nathan BrinkmanAbstract:During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. Plasma Haptoglobin and hemopexin scavenge free hemoglobin and heme, respectively, but can be depleted in hemolytic states. Haptoglobin and hemopexin supplementation protect tissues, including the vasculature, liver and kidneys. It is widely assumed that these protective effects are due primarily to hemoglobin and heme clearance from the vasculature. However, this simple assumption does not account for the consequent cytoprotective adaptation seen in cells and organs. To further address the mechanism, we used a hyperhemolytic murine model (Townes-SS) of sickle cell disease to examine cellular responses to Haptoglobin and hemopexin supplementation. A single infusion of Haptoglobin or hemopexin (± equimolar hemoglobin) in SS-mice increased heme oxygenase-1 (HO-1) in the liver, kidney and skin several fold within 1 hour and decreased nuclear NF-ĸB phospho-p65, and vaso-occlusion for 48 hours after infusion. Plasma hemoglobin and heme levels were not significantly changed 1 hour after infusion of Haptoglobin or hemopexin. Haptoglobin and hemopexin also inhibited hypoxia/reoxygenation and lipopolysaccharide-induced vaso-occlusion in SS-mice. Inhibition of HO-1 activity with tin protoporphyrin blocked the protections afforded by Haptoglobin and hemopexin in SS-mice. The HO-1 reaction product carbon monoxide, fully restored the protection, in part by inhibiting Weibel-Palade body mobilization of P-selectin and von Willebrand factor to endothelial cell surfaces. Thus, the mechanism by which Haptoglobin and hemopexin supplementation in hyperhemolytic SS-mice induces cytoprotective cellular responses is linked to increased HO-1 activity.
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Haptoglobin and hemopexin infusion efficiently activates the nrf2 ho 1 axis and inhibits inflammation and vaso occlusion in murine sickle cell disease
Blood, 2016Co-Authors: John D Belcher, Nathan Brinkman, Chunsheng Chen, Julia Nguyen, Fuad Abdulla, Ping Zhang, Hao Nguyen, Phong Nguyen, Gregory M VercellottiAbstract:Free hemoglobin and hemin, released by red blood cells during intravascular hemolysis, promote vasculopathy, inflammation, thrombosis, and renal injury. Plasma Haptoglobin and hemopexin tightly bind free hemoglobin and hemin, respectively, thwarting these clinical sequelae. In sickle cell disease (SCD), chronic hemolysis can deplete plasma Haptoglobin and hemopexin in humans and mice. To explore mechanisms mediating this protection and provide a basis for supplementation in SCD patients, dorsal skin fold chambers were implanted onto Townes-SS mice and microvascular stasis (% non-flowing venules) was measured in response to a hemoglobin challenge. Human Haptoglobin, hemopexin, or albumin was co-infused with hemoglobin or 1 hour after hemoglobin at equimolar concentrations. Sickle mice co-infused with hemoglobin/Haptoglobin, hemoglobin/hemopexin or hemoglobin/Haptoglobin/hemopexin had less stasis 1 to 4 hours after infusion, compared to albumin- and saline-treated mice (*p Disclosures Belcher:CSL-Behring: Research Funding; Imara: Research Funding. Chen:Imara: Research Funding. Brinkman:CSL-Behring: Employment. Vercellotti:CSL-Behring: Research Funding; Imara: Research Funding.
Barroso, Rogério Magno Do Vale - One of the best experts on this subject based on the ideXlab platform.
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Determinaçao das principais proteínas de fase aguda e do índice prognóstico inflamatório nutricional (IPIN) em cachorrodo-mato (Cerdocyon thous - Linnaeus, 1766)
Universidade Federal de Uberlândia, 2016Co-Authors: Barroso, Rogério Magno Do ValeAbstract:O cachorro-do-mato (Cerdocyon thous - Linnaeus, 1766) é um canídeo de médio porte com distribuição ampla na América do Sul e que ocorre em quase todo o Brasil. Dentre as principais ameaças à sua conservação estão os atropelamentos causados principalmente pela perda de habitat. A escassez de dados laboratoriais de cachorro-do-mato prejudica o atendimento médico veterinário dificultando a aplicação de terapias adequadas. Este trabalho teve como objetivo avaliar os níveis de Proteína C Reativa, Albumina, Pré-albumina, Ceruloplasmina, Haptoglobina e Alfa 1 Glicoproteína Ácida bem como o Indice Prognóstico Inflamatório Nutricional (IPIN) nesta espécie, obtendo portanto uma primeira descrição destes marcadores prognósticos. Foram coletados 1,5 ml de sangue por acesso jugular de oito exemplares de Cachorro-do-mato (Cerdocyon thous) provenientes do acervo do Laboratório de Ensino e Pesquisa em Animais Selvagens (LAPAS) da Faculdade de Medicina Veterinária da Universidade Federal de Uberlândia para exames de rotina. As amostras foram coletadas através da veia jugular após contenção física dos animais e tricotomia da região. Após análise estatística, os valores encontrados foram: albumina: entre 2,7 e 3,0 g/dl, alfa 1 glicoproteína ácida: entre 0,19 e 0,21 g/l, proteína C reativa: entre 1,7 e 2,2, pré-albumina: entre 30 e 35 mg/l e Haptoglobina: entre 0,078 e 0,156 e IPIN ≤ 0,006 sendo considerado normal e valores ≥ 0,006 considerados altos. Esta prima descrição servirá como base para estudos utilizando animais com doenças específicas e, após as análises, comparadas com os valores encontrados neste trabalho verificando se o comportamento segue a semelhança de cães domésticos.The dog-eating fox (Cerdocyon thous - Linnaeus, 1766) is a medium sized canid widely distributed in South America and occurs in almost all of Brazil. Among the main threats to their conservation are the roadkill mainly caused by habitat loss. The shortage of laboratory bush dogs data affect the veterinary medical care hindering the application of appropriate therapies. This study aimed to evaluate the levels of C-reactive protein, albumin, pre-albumin, ceruloplasmin, Haptoglobin and Afla 1 acid glycoprotein and the Prognostic Index Inflammatory Nutritional (IPIN) in this species, thus obtaining a first description of these prognostic markers. They collected 1.5 ml of blood by jugular access 8 of Mato Dogs copies (thous thous) from the Laboratory of collection of Teaching and Research in Wildlife (limpets), Faculty of Veterinary Medicine, Federal University of Uberlândia for exams routine. The samples were collected via the jugular vein after physical restraint of animals and trichotomy of the region. After statistical analysis, the values were: albumin: between 2.7 and 3.0 g / dl, alpha 1-acid glycoprotein: between 0.19 and 0.21 g / l, C-reactive protein: between 1.7 and 2 2, prealbumin between 30 and 35 mg / l Haptoglobin: between 0.078 and 0.156 and IPIN ≤ 0.006 being considered normal and values ≥ 0.006 considered high. This press description will serve as a basis for studies where animals may be used with specific diseases and, after analysis, compared with the values found in this study and verified the behavior follows the likeness of domestic dogs
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Determinação das principais proteínas de fase aguda e do índice prognóstico inflamatório nutricional (IPIN) em cachorro-do-mato (Cerdocyon thous - Linnaeus, 1766)
'EDUFU - Editora da Universidade Federal de Uberlandia', 2016Co-Authors: Barroso, Rogério Magno Do ValeAbstract:The dog-eating fox (Cerdocyon thous - Linnaeus, 1766) is a medium sized canid widely distributed in South America and occurs in almost all of Brazil. Among the main threats to their conservation are the roadkill mainly caused by habitat loss. The shortage of laboratory bush dogs data affect the veterinary medical care hindering the application of appropriate therapies. This study aimed to evaluate the levels of C-reactive protein, albumin, pre-albumin, ceruloplasmin, Haptoglobin and Afla 1 acid glycoprotein and the Prognostic Index Inflammatory Nutritional (IPIN) in this species, thus obtaining a first description of these prognostic markers. They collected 1.5 ml of blood by jugular access 8 of Mato Dogs copies (thous thous) from the Laboratory of collection of Teaching and Research in Wildlife (limpets), Faculty of Veterinary Medicine, Federal University of Uberlândia for exams routine. The samples were collected via the jugular vein after physical restraint of animals and trichotomy of the region. After statistical analysis, the values were: albumin: between 2.7 and 3.0 g / dl, alpha 1-acid glycoprotein: between 0.19 and 0.21 g / l, C-reactive protein: between 1.7 and 2 2, prealbumin between 30 and 35 mg / l Haptoglobin: between 0.078 and 0.156 and IPIN ≤ 0.006 being considered normal and values ≥ 0.006 considered high. This press description will serve as a basis for studies where animals may be used with specific diseases and, after analysis, compared with the values found in this study and verified the behavior follows the likeness of domestic dogs.Tese (Doutorado)O cachorro-do-mato (Cerdocyon thous - Linnaeus, 1766) é um canídeo de médio porte com distribuição ampla na América do Sul e que ocorre em quase todo o Brasil. Dentre as principais ameaças à sua conservação estão os atropelamentos causados principalmente pela perda de habitat. A escassez de dados laboratoriais de cachorro-do-mato prejudica o atendimento médico veterinário dificultando a aplicação de terapias adequadas. Este trabalho teve como objetivo avaliar os níveis de Proteína C Reativa, Albumina, Pré-albumina, Ceruloplasmina, Haptoglobina e Alfa 1 Glicoproteína Ácida bem como o Indice Prognóstico Inflamatório Nutricional (IPIN) nesta espécie, obtendo portanto uma primeira descrição destes marcadores prognósticos. Foram coletados 1,5 ml de sangue por acesso jugular de oito exemplares de Cachorro-do-mato (Cerdocyon thous) provenientes do acervo do Laboratório de Ensino e Pesquisa em Animais Selvagens (LAPAS) da Faculdade de Medicina Veterinária da Universidade Federal de Uberlândia para exames de rotina. As amostras foram coletadas através da veia jugular após contenção física dos animais e tricotomia da região. Após análise estatística, os valores encontrados foram: albumina: entre 2,7 e 3,0 g/dl, alfa 1 glicoproteína ácida: entre 0,19 e 0,21 g/l, proteína C reativa: entre 1,7 e 2,2, pré-albumina: entre 30 e 35 mg/l e Haptoglobina: entre 0,078 e 0,156 e IPIN ≤ 0,006 sendo considerado normal e valores ≥ 0,006 considerados altos. Esta prima descrição servirá como base para estudos utilizando animais com doenças específicas e, após as análises, comparadas com os valores encontrados neste trabalho verificando se o comportamento segue a semelhança de cães domésticos
