Evaluation of cardioprotective effects of carvedilol in dogs receiving doxorubicin chemotherapy: A prospective, randomized, double-blind, placebo controlled pilot study.

The aim of this pilot study was to evaluate the cardioprotective effects of carvedilol in dogs receiving doxorubicin chemotherapy and provide suggestions to future studies based on results and limitations of our study. Thirteen dogs were randomized into two experimental groups: 6 dogs in carvedilol group and 7 dogs in placebo group. In carvedilol group, 0.39 mg/kg ± 0.04 twice-daily oral carvedilol was started on the day of the first doxorubicin treatment and continued throughout the chemotherapy protocol until the final cardiological evaluation. Cardiological evaluations were performed before the first doxorubicin administration and then 10 to 15 days after each subsequent dose. Troponin I and oxidative stress tests were performed with serum collected from dogs at the initial and final cardiological evaluation. Carvedilol produced some echocardiographic and electrocardiographic changes (reduced E velocity and E/IVRT ratio, as well reduced heart rate and increased PR and QT interval) due to its beta-block effect. In placebo group Doppler study showed a significant increase in mitral flow deceleration time (EDT), as well increased amplitude of the S wave in the right, and R wave in the left, precordial chest leads. There were significant difference in the EDT, E/IVRT and A' velocity, as well heart rate, PR interval and R wave in V4/CV6LU precordial chest lead between groups. In conclusion, some indexes of diastolic function and in precordial chest leads were less affected by doxorubicin in carvedilol than in control group. This suggests that carvedilol may have a beneficial effect in canine cancer patients receiving doxorubicin.

Linfonodo axilar como sentinela de neoplasia mamária em cadelas / Axillary lymph node as sentinel for mammary neoplasia in bitches

Linfonodo axilar como sentinela de neoplasia mamária em cadelas. O estudo dos tumores de mama em cadelas é de grande importância devido à alta frequência com que surgem na clínica de pequenos animais. O presente estudo teve como objetivo avaliar a importância do linfonodo axilar como sentinela em neoplasias mamárias de cadelas. Foram avaliadas 49 fêmeas com neoplasia mamária, submetidas à mastectomia unilateral total, utilizando o corante azul patente para a identificação do linfonodo axilar, o qual foi submetido à análise histopatológica com a coloração de hematoxilina-eosina e imuno-histoquímica (IHQ) com anticorpo citoqueratina (AE1/AE3) para procura de metástase. Oito cadelas apresentaram metástases em linfonodo axilar, sendo sete detectadas por histopatologia e por IHQ e uma somente pela IHQ (micrometástase). Uma paciente que apresentava tumor em mamas abdominal caudal e inguinal tinha metástase no linfonodo axilar e inguinal. Assim, observa-se que o tumor pode causar alteração na drenagem linfática provocando metástase em linfonodos que normalmente não drenam determinadas mamas, por isso a retirada do linfonodo axilar deve ser incluída como técnica de rotina para permitir melhor estadiamento das neoplasias mamárias de cadelas.(AU)

Mammary tumors research in bitches is important due to their high incidence. The aim of this study was to evaluate the importance of the axillary lymph node as a sentinel lymph node for mammary neoplasms in female dogs. Forty-nine bitches with mammary neoplasia were submitted to total unilateral mastectomy, and the axillary lymph node was identified using the patent blue dye. This lymph node was processed routinely for histopathological analysis and stained with hematoxylin-eosin and by immunohistochemistry (IHC) with cytokeratin antibody (AE1/AE3) to search for metastasis. Eight dogs had axillary lymph node metastases, seven of which were detected by histopathology and by IHC and only one by IHC (micrometastasis). One dog who presented tumor in caudal and inguinal abdominal mammary glands had metastases in the axillary and inguinal lymph nodes. It is concluded that the mammary tumor can cause alteration in lymphatic drainage leading to metastases in lymph nodes which normally do not drain certain glands; so the removal of the axillary lymph node should be included as a routine technique to allow better staging of mammary neoplasms of bitches.(AU)

Paraneoplastic hematological, biochemical, and hemostatic abnormalities in female dogs with mammary neoplasms / Anormalidades hematológicas, bioquímicas e hemostáticas de origem paraneoplásica em fêmeas caninas com neoplasia mamária

Paraneoplastic laboratory abnormalities are identified in several types of cancers in dogs and cats. In veterinary medicine, particularly in mammary cancer, there are few studies that correlate abnormal laboratory findings with tumor type and staging. The aim of this study was to evaluate hematological, biochemical, and hemostatic abnormalities and correlate them with mammary tumor staging in female dogs with mammary cancer. Blood samples from 24 female dogs were evaluated, and the hematological, biochemical, and hemostatic parameters were correlated with tumor staging obtained by physical examination, imaging exams, and histopathological surgical biopsies. The groups were organized according to tumor staging: group 1 (stages I and II), group 2 (stage III), and group 3 (stages IV and V). Anemia, neutrophilic leukocytosis, monocytosis, eosinophilia, thrombocytosis, hypoalbuminemia, hypocalcemia, hypoglycemia, and low blood urea were observed. The variables MCHC, TPP, and RDW were correlated with tumor staging with no clinical relevance. Thrombin time and fibrinogen were significant between the groups in the coagulation test, being associated with tumor staging. The findings suggest influence of the proinflammatory cytokines released during tumor growth.(AU)

Alterações laboratoriais de origem paraneoplásica são identificadas em diversos tipos de câncer de cães e gatos. Na medicina veterinária, existem poucos estudos que correlacionam os achados laboratoriais anormais com o tipo e estadiamento tumorais, principalmente em cadelas com neoplasia mamária. O objetivo deste estudo foi avaliar as alterações hematológicas, bioquímicas e hemostáticas em cadelas com neoplasia mamária e relacioná-las com o estadiamento tumoral. Foram coletadas amostras de sangue de 24 fêmeas caninas, e os parâmetros hematológicos, bioquímicos e hemostáticos obtidos foram relacionados com o estadiamento tumoral, realizado através do exame físico, exames de imagem e avaliação histopatológica após remoção cirúrgica. Os grupos foram organizados de acordo com o estadiamento tumoral em: Grupo 1 (estádios I e II), grupo 2 (estádio III) e grupo 3 (estádios IV e V). Observou-se anemia, leucocitose neutrofílica, monocitose, eosinofilia, trombocitose, hipoalbuminemia, hipocalcemia, hipoglicemia e diminuição de ureia sanguínea. As variáveis CHCM, PPT e RDW foram relacionadas com o estadiamento tumoral, porém sem relevância clínica. Nos testes de coagulação, o TT e o fibrinogênio apresentaram diferença significativa entre os grupos, sendo associado com estadiamento tumoral. Os resultados sugerem influência das citocinas pró-inflamatórias liberadas durante o crescimento do tumor.(AU)

Methionine-induced hyperhomocysteinemia reverts fibrinolytic pathway activation in a murine model of acute promyelocytic leukemia.

Increased fibrinolysis is an important component of acute promyelocytic leukemia (APL) bleeding diathesis. APL blasts overexpress annexin II (ANXII), a receptor for tissue plasminogen activator (tPA), and plasminogen, thereby increasing plasmin generation. Previous studies suggested that ANXII plays a pivotal role in APL coagulopathy. ANXII binding to tPA can be inhibited by homocysteine and hyperhomocysteinemia can be induced by L-methionine supplementation. In the present study, we used an APL mouse model to study ANXII function and the effects of hyperhomocysteinemia in vivo. Leukemic cells expressed higher ANXII and tPA plasma levels (11.95 ng/mL in leukemic vs 10.74 ng/mL in wild-type; P = .004). In leukemic mice, administration of L-methionine significantly increased homocysteine levels (49.0 µmol/mL and < 6.0 µmol/mL in the treated and nontreated groups, respectively) and reduced tPA levels to baseline concentrations. The latter were also decreased after infusion of the LCKLSL peptide, a competitor for the ANXII tPA-binding site (11.07 ng/mL; P = .001). We also expressed and purified the p36 component of ANXII in Pichia methanolica. The infusion of p36 in wild-type mice increased tPA and thrombin-antithrombin levels, and the latter was reversed by L-methionine administration. The results of the present study demonstrate the relevance of ANXII in vivo and suggest that methionine-induced hyperhomocysteinemia may reverse hyperfibrinolysis in APL.