Claudia Mori | Universidade de São Paulo (original) (raw)

Papers by Claudia Mori

Research paper thumbnail of Supplemental material for Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization

Supplemental Material for Combination of ketamine and xylazine with opioids and acepromazine in r... more Supplemental Material for Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization by Jilma Alemán-Laporte, Luciana A Bandini, Mariana SA Garcia-Gomes, Dennis A Zanatto, Denise T Fantoni, Marco A Amador Pereira, Pedro E Navas-Suárez, Thiago Berti Kirsten, Randall R. Jimenez, Gilbert Alvarado and Claudia Cabrera Mori in Laboratory Animals

Research paper thumbnail of Mouse Behavior in the Open-field Test after Meloxicam Administration

Journal of the American Association for Laboratory Animal Science

Several analgesics are suggested for pain management in mice. Nonsteroidal antiinflammatories (NS... more Several analgesics are suggested for pain management in mice. Nonsteroidal antiinflammatories (NSAIDs), such as meloxicamcan be administered for the treatment of inflammation and acute pain; however, several side effects can occur which include gastrointestinal ulceration and renal and hepatic toxicity. We previously performed a pilot study to test the antinociceptiveactivity of meloxicam in mice, but we observed behavioral changes in unoperated control mice. These observations spurred further investigation. One hypothesis for the result was potential differences in formulation between commercial brands of meloxicam. Thus, this current study aimed to evaluate the effects of 3 different commercial brands of meloxicam (20 mg/kg) in the general activity of mice using the open field test. Our results showed that meloxicam had several effects on mouse behavior and caused the formation of skin lesions at the injection site, depending on the brand of the drug. The most significant adverse ...

Research paper thumbnail of Evaluation of the Biocompatibility and Osteoconduction of the Carbon Nanotube, Chitosan and Hydroxyapatite Nanocomposite with or without Mesenchymal Stem Cells as a Scaffold for Bone Regeneration in Rats

Background: Bone substitutes have been developed to assist bone regeneration in orthopedic surger... more Background: Bone substitutes have been developed to assist bone regeneration in orthopedic surgeries. Mesenchymal stem cells can be added to these biomaterials to enhance bone regeneration. This study aimed to evaluate the biocompatibility and osteoconduction of a carbon nanotube, chitosan, and hydroxyapatite nanocomposite (CNCHN) that had either been enriched or not enriched with sheep bone marrow mesenchymal stem cells (BM-MSCs) in rats. Methods: A total of sixty rats were divided into groups, and an implant with or without BM-MSCs was performed subcutaneously in 20 animals (euthanized after 7 and 30 days), comparing them to 10 control animals, and in the calvaria of 20 animals (euthanized after 20 and 60 days), comparing to with 10 control animals. Subcutaneous and calvaria histologies were performed after euthanasia. Results: The subcutaneous tissue showed that CNCHN did not prompt an exacerbated inflammatory response or signs of necrosis. The histomorphological analysis by the ...

Research paper thumbnail of Effects of Three Consecutive Days of Morphine or Methadone Administration on Analgesia and Open-Field Activity in Mice with Ehrlich Carcinoma

Journal of the American Association for Laboratory Animal Science : JAALAS, 2021

This study assessed the exploratory behavioral responses in BALB/c mice inoculated with Ehrlich a... more This study assessed the exploratory behavioral responses in BALB/c mice inoculated with Ehrlich ascitic carcinoma after 3consecutive days of treatment with morphine or methadone. Fifty-three female mice, 60 ± 10 d old, were used. Seven days after intraperitoneal tumor inoculation (2 × 106 cells), the animals were randomized into 7 groups: morphine 5 mg/kg (MO5), morphine 7.5 mg/kg (MO7.5), morphine 10 mg/kg (MO10), methadone 2.85 mg/kg (ME2.85), methadone 4.3 mg/kg (ME4.3), methadone5.7 mg/kg (ME5.7), and 0.9% NaCl (Saline) (n = 7). Drug treatments were administered subcutaneously every 6 h for 3 d. The animals were evaluated for analgesia using the mouse grimace scale (MGS) and for general activity using the open field test. The MGS was performed before tumor inoculation (day 0), on day 7 at 40, 90, 150, 240, and 360 min after drug injection, and on days 8 and 9 at 40, 150, 240, and 360 min after drug injection. The open field test was performed before tumor inoculation(day 0), on ...

Research paper thumbnail of Higher susceptibility of spontaneous and NNK‐induced lung neoplasms in connexin 43 deficient CD1× AJ F1 mice: Paradoxical expression of connexin 43 during lung carcinogenesis

Connexins (Cxs) are proteins that form the communicating gap junctions, and reportedly have a rol... more Connexins (Cxs) are proteins that form the communicating gap junctions, and reportedly have a role in carcinogenesis. Here, we evaluated the importance of Connexin43 (Cx43) in spontaneous and 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone (NNK)-induced lung carcinogenesis. Male wild-type (Cx43 þ/þ) and hemizygote (Cx43 þ/À) CD1 Â AJ F1 mice were injected with NNK or saline. After 60 weeks mice were euthanized; lung nodules were counted, measured, and fixed in formalin or snap frozen. Immunohistochemistry for Cx43 and Beta-catenin (bcatenin) was performed and Cx43 mRNA expression was evaluated by real-time PCR. Cx43 deletion significantly increased the incidence and number of spontaneous nodules in the CD1 Â AJ F1 mice and the number of gross lesions and the aggressiveness of lesions in NNK-treated mice. Cx43 mRNA increased significantly and was correlated with the aggressiveness of tumors, although lesions from Cx43 þ/À mice expressed less Cx43 RNAm than their counterparts. Lung parenchyma presented a Cx43 immunostaining pattern with points or plaques between cells. In hyperplasias and adenomas, Cx43 was found in the membrane and in cytoplasm. Malignant lesions presented increased Cx43 in cytoplasm and a few membrane spots of immunostaining. b-catenin was weakly expressed in lung parenchyma. Though hyperplasias presented some cells with nuclear b-catenin, NNK-induced tumors contained a higher number of this staining pattern. Also, no difference in b-catenin occurred between both genotypes independently of the histological grade. In summary, our results indicate that Cx43 acts as a tumor suppressor gene in early lung tumorigenesis and loses this property in advanced carcinogenesis. Therefore, Cxs are better classified as conditional tumor suppressors.

Research paper thumbnail of A Simple and Fast Battery Test for Phenotypic Characterization of Mice

Research paper thumbnail of Capacitação em Ciência de Animais de Laboratório

Revista de Educação Continuada em Medicina Veterinária e Zootecnia do CRMV-SP

A Ciência de Animais de Laboratório envolve uma abordagem multidisciplinar com conhecimento do mo... more A Ciência de Animais de Laboratório envolve uma abordagem multidisciplinar com conhecimento do modelo animal e suas necessidades etológicas espécie-específicas, refinamento de experimentos que melhoram o bem-estar animal com reconhecimento e tratamento da dor, anestesia e eutanásia, bem como delineamento experimental e análise estatística dos resultados experimentais. Para atender à essas necessidades, pessoas que realizam, participam, supervisionam procedimentos experimentais em animais, ou cuidam de animais de laboratório, devem receber treinamento, com programas voltados à implementação dos 3Rs e promoção do bem-estar dos animais de laboratório, garantindo assim a qualidade e reprodutibilidade de experimentos com benefícios éticos, científicos e econômicos. Nos países da Europa e nos Estados Unidos, e requerido mais recentemente pelo Conselho Nacional de Controle de Experimentação Animal (CONCEA) no Brasil, um veterinário com experiência em medicina de animais de laboratório prec...

Research paper thumbnail of Quality of Adherence to the ARRIVE Guidelines in the Material and Methods Section in Studies Where Swine Were Used as Surgical Biomodels: A Systematic Review (2013–2018)

Animals

Over the last two decades, pigs have become animal biomodels widely used for the investigation an... more Over the last two decades, pigs have become animal biomodels widely used for the investigation and practice of surgical techniques because of their great physiological and anatomical similarities to humans. Even though many of these studies must be carried out later in humans, the description of basic information is limited, making exact repetitions of the reported experimental methods impossible. In this review, 108 studies from 2013 to 2018 were considered to determine the quality of adherence to the ARRIVE guidelines in the reports of the methodologies. The majority of the studies lacked the details recommended in the ARRIVE guidelines regarding data directly related to the welfare of animals undergoing surgery and those about anesthetic protocols and analgesics. Information related to sample size calculation and housing and husbandry conditions was also very limited. We believe that the ARRIVE guidelines are an excellent tool for good-quality reporting. We encourage scientists t...

Research paper thumbnail of Inhibitory effects of Euphorbia tirucalli latex on murine B16/F10 melanoma cells and lung metastasis

Molecular and Clinical Oncology

Euphorbia tirucalli (E. tirucalli) is a tropical and subtropical plant that produces a latex whic... more Euphorbia tirucalli (E. tirucalli) is a tropical and subtropical plant that produces a latex which is used for several purposes. The components of E. tirucalli latex include triterpenes, diterpenes and steroids. The aim of the present study was to evaluate the effects of diluted E. tirucalli latex on murine B16/F10 melanoma cells and lung metastasis. For this purpose, an in vitro study was first performed, in which B16/F10 cells were treated with diluted (1/2 to 1/11,192) E. tirucalli latex. In a second study, B16/F10 melanoma cells were inoculated into the tail vein of mice to generate lung metastases; the mice then received 0.467 µg of latex diluted in 200 ml saline by gavage for 14 days. A significant decrease in B16/F10 cell viability was observed using the MTT assay at 24 and 48 h after treatment with E. tirucalli latex. In addition, a significant decrease in the volume fraction occupied by B16/F10 metastatic colonies in the lungs was observed in mice treated with E. tirucalli latex. These results confirm the antineoplastic effects of diluted E. tirucalli latex.

Research paper thumbnail of Decontamination of genetically modified mice strains by embryo transfer for obtaining SPF colonies in a Brazilian animal facility

Brazilian Journal of Veterinary Research and Animal Science

The introduction of new strains of mice in specific pathogen-free (SPF) animal facilities should ... more The introduction of new strains of mice in specific pathogen-free (SPF) animal facilities should be performed carefully to avoid breaking sanitary barriers. To meet this need, animals should be rederived to reduce infection risk and thus avoid research interference caused by loss of animal health status and welfare. The objective of this study was to implement mice embryo transfer in the laboratory mouse facility of the Department of Immunology at the Institute of Biomedical Sciences/University of São Paulo, Brazil. Embryo transfers were performed to rederive genetically modified mouse strains with undefined sanitary status, received from different research and educational institutions. Fertilized eggs at two-cell stage were obtained by natural means and transferred into the oviducts of SPF pseudo-pregnant female mice. All surgical procedures were performed under aseptic conditions. A total of 625 embryos were transferred into therecipients. 148 pups were born, of which 140 were rea...

Research paper thumbnail of Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization

Research paper thumbnail of Genetic and behavioral characterization of a Kmt2d mouse mutant, a new model for Kabuki Syndrome

Genes, Brain and Behavior

Research paper thumbnail of Abstract 819: Transcriptomic profiling of two canine mammary cancer cell lines for translational oncology studies

Research paper thumbnail of A rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant

Archives of Virology

Rabies is one of the most important zoonotic diseases and is caused by several rabies virus (RABV... more Rabies is one of the most important zoonotic diseases and is caused by several rabies virus (RABV) variants. These variants can exhibit differences in neurovirulence, and few studies have attempted to evaluate the neuroinvasiveness of variants derived from vampire bats and wild carnivores. The aim of this study was to evaluate the neuropathogenesis of infection with two Brazilian RABV street variants (variant 3 and crab-eating fox) in mice. BALB/c mice were inoculated with RABV through the footpad, with the 50% mouse lethal dose (LD50) determined by intracranial inoculation. The morbidity of rabies in mice infected with variant 3 and the crab-eating fox strain was 100% and 50%, respectively, with an incubation period of 7 and 6 days post-inoculation (dpi), respectively. The clinical disease in mice was similar with both strains, and it was characterized initially by weight loss, ruffled fur, hunched posture, and hind limb paralysis progressing to quadriplegia and recumbency at 9 to 12 dpi. Histological lesions within the central nervous system (CNS) characterized by nonsuppurative encephalomyelitis with neuronal degeneration and necrosis were observed in mice infected with variant 3 and those infected with the crab-eating fox variant. However, lesions and the presence of RABV antigen, were more widespread within the CNS of variant-3-infected mice, whereas in crab-eating fox-variant-infected mice, RABV antigens were more restricted to caudal areas of the CNS, such as the spinal cord and brainstem. In conclusion, the results shown here demonstrate that the RABV vampire bat strain (variant 3) has a higher potential for neuroinvasiveness than the carnivore variant.

Research paper thumbnail of Experimental infestation of Gallus gallus with Ornithodoros (Alectorobius) amblus (Ixodoidea: Argasidae)

Journal of medical entomology, 1997

Ornithodoros (Alectorobius) amblus Chamberlin 1920 specimens were collected from a seagull (Larus... more Ornithodoros (Alectorobius) amblus Chamberlin 1920 specimens were collected from a seagull (Larus spp.) nest in northern Chile. This reports the occurrence of this species outside Peru. The biology of 79 specimens reared under laboratory conditions at 27 degrees C, 75-80% RH, and total darkness was determined. A 13% mortality rate from larval to adult was observed. Larval ticks were fed on chicks, Gallus gallus domesticus; and nymphs and adults were fed on chickens. We recorded the number of eggs per female per gonotrophic cycle and the mean duration of the periods of preoviposition, oviposition, and incubation. The total duration of their life cycle ranged from 111 to 239 d, depending on the number of molts. Males were found after the 4th molt, and after the 5th molt the proportion of females was greater than that of males or remaining nymphs. The feeding period of larvae was 4-6 d, N1 nymphs do not feed. The N2-N6 nymphs, males and females, had a 10- to 60-min feeding period. From...

Research paper thumbnail of Avaliação da etiopagenia da encefalite causada pelo herpesvírus equino tipo 1 utilizando um modelo murino de neuroinfecção

pela orientação, amizade e confiança. À Profa. Dra. Silvana Gorniak, minha segunda orientadora, p... more pela orientação, amizade e confiança. À Profa. Dra. Silvana Gorniak, minha segunda orientadora, pela amizade, incentivo e por ter abraçado a causa de produzir modelos animais com qualidade para a pesquisa. Ao Instituto Biológico de São Paulo, em nome das pesquisadoras Elenice M. S. Cunha, Maria do Carmo C. S. H. Lara e Eliana M.C.Villalobos pela valiosa colaboração em todas as etapas deste trabalho e pela oportunidade de realizar parte dos experimentos no Laboratório de Raiva e Encefalites. Aos professores do Departamento de Patologia Maria Lúcia Zaidan Dagli, Luciano Freitas Felício, Helenice Souza Spinosa e João Palermo Neto pelos ensinamentos transmitidos, incentivo e apoio durante todos esses anos de convívio e pela oportunidade da realização deste trabalho.

Research paper thumbnail of Detecção do DNA do herpesvírus eqüino 1 pela reação em cadeia pela polimerase em cavalos inoculados com a estirpe brasileira A4/72

Brazilian Journal of Veterinary Research and Animal Science, 2009

Research paper thumbnail of Altered expression of connexins in urethane-induced mouse lung adenomas

Life Sciences, Feb 11, 2006

Lung carcinogenesis is a multistep process whose molecular alterations can be studied in mouse mo... more Lung carcinogenesis is a multistep process whose molecular alterations can be studied in mouse models. Urethane, a specific lung tumor carcinogen, can induce adenomas in mice. Mouse lung alveolar cells reportedly generate lung neoplasms, and express connexins 26, 32, 43 and 46. The aim of the present study was to evaluate the expression of connexins in urethane-induced lung adenomas. Fifteen-day-old CD1 male mice received 2 i.p. injections of urethane (1.5 g/kg bw). The mice were euthanized 25 weeks after urethane injection, and lung adenomas were quantified. Lung tissue and lung adenomas were harvested and the RNA was extracted. The expression of connexins 26, 32, 43 and 46 was evaluated by Real-Time PCR, and these proteins were identified by Western blot. Immunohistochemistry revealed the distribution pattern of these connexins in lung tissue and adenomas. The treatment with urethane was associated with the downregulation of Cx26, 32 and 46 expressions, and with the upregulation of Cx43 expression in lung tissue. Surprisingly, in lung adenomas Cx32 and Cx43 expressions were not detected, although the expression of connexins 26 and 46 was present. Western blot and immunohistochemistry corroborated the RT-PCR data. These results may indicate a role of Cx32 and Cx43 in urethane-induced lung carcinogenesis, since their absence may contribute to the development of urethane induced lung tumors. The role of Cx26 and Cx46 is yet to be determined.

Research paper thumbnail of Molecular characterization of Brazilian equid herpesvirus type 1 strains based on neuropathogenicity markers

Brazilian Journal of Microbiology, 2015

Partial nucleotide sequences of ORF72 (glycoprotein D, gD), ORF64 (infected cell protein 4, ICP4)... more Partial nucleotide sequences of ORF72 (glycoprotein D, gD), ORF64 (infected cell protein 4, ICP4) and ORF30 (DNA polymerase) genes were compared with corresponding sequences of EHV-1 reference strains to characterize the molecular variability of Brazilian strains. Virus isolation assays were applied to 74 samples including visceral tissue, total blood, cerebrospinal fluid (CSF) and nasal swabs of specimens from a total of 64 animals. Only one CSF sample (Iso07/05 strain) was positive by virus isolation in cell culture. EHV-1 Iso07/05 neurologic strain and two abortion visceral tissues samples (Iso11/06 and Iso33/06) were PCR-positive for ORF33 (glycoprotein B, gB) gene of EHV-1. A sequence analysis of the ORF72, ORF64 and ORF30 genes from three EHV-1 archival strains (A3/97, A4/72, A9/92) and three clinical samples (Iso07/05, Iso11/06 and Iso33/06) suggested that among Brazilian EHV-1 strains, the amplified region of the gD gene sequence is highly conserved. Additionally, the analysis of ICP4 gene showed high nucleotide and amino acid identities when compared with genotype P strains, suggesting that the EHV-1 Brazilian strains belonged to the same group. All the EHV-1 Brazilian strains were classified as non-neuropathogenic variants (N752) based on the ORF30 analysis. These findings indicate a high conservation of the gD-, ICP4- and ORF30-encoding sequences. Different pathotypes of the EHV-1 strain might share identical genes with no specific markers, and tissue tropism is not completely dependent on the gD envelope, immediate-early ICP4 and DNA polymerase proteins.

Research paper thumbnail of Altered expression of connexins in urethane-induced mouse lung adenomas

Life Sciences, 2006

Lung carcinogenesis is a multistep process whose molecular alterations can be studied in mouse mo... more Lung carcinogenesis is a multistep process whose molecular alterations can be studied in mouse models. Urethane, a specific lung tumor carcinogen, can induce adenomas in mice. Mouse lung alveolar cells reportedly generate lung neoplasms, and express connexins 26, 32, 43 and 46. The aim of the present study was to evaluate the expression of connexins in urethane-induced lung adenomas. Fifteen-day-old CD1 male mice received 2 i.p. injections of urethane (1.5 g/kg bw). The mice were euthanized 25 weeks after urethane injection, and lung adenomas were quantified. Lung tissue and lung adenomas were harvested and the RNA was extracted. The expression of connexins 26, 32, 43 and 46 was evaluated by Real-Time PCR, and these proteins were identified by Western blot. Immunohistochemistry revealed the distribution pattern of these connexins in lung tissue and adenomas. The treatment with urethane was associated with the downregulation of Cx26, 32 and 46 expressions, and with the upregulation of Cx43 expression in lung tissue. Surprisingly, in lung adenomas Cx32 and Cx43 expressions were not detected, although the expression of connexins 26 and 46 was present. Western blot and immunohistochemistry corroborated the RT-PCR data. These results may indicate a role of Cx32 and Cx43 in urethane-induced lung carcinogenesis, since their absence may contribute to the development of urethane induced lung tumors. The role of Cx26 and Cx46 is yet to be determined.

Research paper thumbnail of Supplemental material for Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization

Supplemental Material for Combination of ketamine and xylazine with opioids and acepromazine in r... more Supplemental Material for Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization by Jilma Alemán-Laporte, Luciana A Bandini, Mariana SA Garcia-Gomes, Dennis A Zanatto, Denise T Fantoni, Marco A Amador Pereira, Pedro E Navas-Suárez, Thiago Berti Kirsten, Randall R. Jimenez, Gilbert Alvarado and Claudia Cabrera Mori in Laboratory Animals

Research paper thumbnail of Mouse Behavior in the Open-field Test after Meloxicam Administration

Journal of the American Association for Laboratory Animal Science

Several analgesics are suggested for pain management in mice. Nonsteroidal antiinflammatories (NS... more Several analgesics are suggested for pain management in mice. Nonsteroidal antiinflammatories (NSAIDs), such as meloxicamcan be administered for the treatment of inflammation and acute pain; however, several side effects can occur which include gastrointestinal ulceration and renal and hepatic toxicity. We previously performed a pilot study to test the antinociceptiveactivity of meloxicam in mice, but we observed behavioral changes in unoperated control mice. These observations spurred further investigation. One hypothesis for the result was potential differences in formulation between commercial brands of meloxicam. Thus, this current study aimed to evaluate the effects of 3 different commercial brands of meloxicam (20 mg/kg) in the general activity of mice using the open field test. Our results showed that meloxicam had several effects on mouse behavior and caused the formation of skin lesions at the injection site, depending on the brand of the drug. The most significant adverse ...

Research paper thumbnail of Evaluation of the Biocompatibility and Osteoconduction of the Carbon Nanotube, Chitosan and Hydroxyapatite Nanocomposite with or without Mesenchymal Stem Cells as a Scaffold for Bone Regeneration in Rats

Background: Bone substitutes have been developed to assist bone regeneration in orthopedic surger... more Background: Bone substitutes have been developed to assist bone regeneration in orthopedic surgeries. Mesenchymal stem cells can be added to these biomaterials to enhance bone regeneration. This study aimed to evaluate the biocompatibility and osteoconduction of a carbon nanotube, chitosan, and hydroxyapatite nanocomposite (CNCHN) that had either been enriched or not enriched with sheep bone marrow mesenchymal stem cells (BM-MSCs) in rats. Methods: A total of sixty rats were divided into groups, and an implant with or without BM-MSCs was performed subcutaneously in 20 animals (euthanized after 7 and 30 days), comparing them to 10 control animals, and in the calvaria of 20 animals (euthanized after 20 and 60 days), comparing to with 10 control animals. Subcutaneous and calvaria histologies were performed after euthanasia. Results: The subcutaneous tissue showed that CNCHN did not prompt an exacerbated inflammatory response or signs of necrosis. The histomorphological analysis by the ...

Research paper thumbnail of Effects of Three Consecutive Days of Morphine or Methadone Administration on Analgesia and Open-Field Activity in Mice with Ehrlich Carcinoma

Journal of the American Association for Laboratory Animal Science : JAALAS, 2021

This study assessed the exploratory behavioral responses in BALB/c mice inoculated with Ehrlich a... more This study assessed the exploratory behavioral responses in BALB/c mice inoculated with Ehrlich ascitic carcinoma after 3consecutive days of treatment with morphine or methadone. Fifty-three female mice, 60 ± 10 d old, were used. Seven days after intraperitoneal tumor inoculation (2 × 106 cells), the animals were randomized into 7 groups: morphine 5 mg/kg (MO5), morphine 7.5 mg/kg (MO7.5), morphine 10 mg/kg (MO10), methadone 2.85 mg/kg (ME2.85), methadone 4.3 mg/kg (ME4.3), methadone5.7 mg/kg (ME5.7), and 0.9% NaCl (Saline) (n = 7). Drug treatments were administered subcutaneously every 6 h for 3 d. The animals were evaluated for analgesia using the mouse grimace scale (MGS) and for general activity using the open field test. The MGS was performed before tumor inoculation (day 0), on day 7 at 40, 90, 150, 240, and 360 min after drug injection, and on days 8 and 9 at 40, 150, 240, and 360 min after drug injection. The open field test was performed before tumor inoculation(day 0), on ...

Research paper thumbnail of Higher susceptibility of spontaneous and NNK‐induced lung neoplasms in connexin 43 deficient CD1× AJ F1 mice: Paradoxical expression of connexin 43 during lung carcinogenesis

Connexins (Cxs) are proteins that form the communicating gap junctions, and reportedly have a rol... more Connexins (Cxs) are proteins that form the communicating gap junctions, and reportedly have a role in carcinogenesis. Here, we evaluated the importance of Connexin43 (Cx43) in spontaneous and 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone (NNK)-induced lung carcinogenesis. Male wild-type (Cx43 þ/þ) and hemizygote (Cx43 þ/À) CD1 Â AJ F1 mice were injected with NNK or saline. After 60 weeks mice were euthanized; lung nodules were counted, measured, and fixed in formalin or snap frozen. Immunohistochemistry for Cx43 and Beta-catenin (bcatenin) was performed and Cx43 mRNA expression was evaluated by real-time PCR. Cx43 deletion significantly increased the incidence and number of spontaneous nodules in the CD1 Â AJ F1 mice and the number of gross lesions and the aggressiveness of lesions in NNK-treated mice. Cx43 mRNA increased significantly and was correlated with the aggressiveness of tumors, although lesions from Cx43 þ/À mice expressed less Cx43 RNAm than their counterparts. Lung parenchyma presented a Cx43 immunostaining pattern with points or plaques between cells. In hyperplasias and adenomas, Cx43 was found in the membrane and in cytoplasm. Malignant lesions presented increased Cx43 in cytoplasm and a few membrane spots of immunostaining. b-catenin was weakly expressed in lung parenchyma. Though hyperplasias presented some cells with nuclear b-catenin, NNK-induced tumors contained a higher number of this staining pattern. Also, no difference in b-catenin occurred between both genotypes independently of the histological grade. In summary, our results indicate that Cx43 acts as a tumor suppressor gene in early lung tumorigenesis and loses this property in advanced carcinogenesis. Therefore, Cxs are better classified as conditional tumor suppressors.

Research paper thumbnail of A Simple and Fast Battery Test for Phenotypic Characterization of Mice

Research paper thumbnail of Capacitação em Ciência de Animais de Laboratório

Revista de Educação Continuada em Medicina Veterinária e Zootecnia do CRMV-SP

A Ciência de Animais de Laboratório envolve uma abordagem multidisciplinar com conhecimento do mo... more A Ciência de Animais de Laboratório envolve uma abordagem multidisciplinar com conhecimento do modelo animal e suas necessidades etológicas espécie-específicas, refinamento de experimentos que melhoram o bem-estar animal com reconhecimento e tratamento da dor, anestesia e eutanásia, bem como delineamento experimental e análise estatística dos resultados experimentais. Para atender à essas necessidades, pessoas que realizam, participam, supervisionam procedimentos experimentais em animais, ou cuidam de animais de laboratório, devem receber treinamento, com programas voltados à implementação dos 3Rs e promoção do bem-estar dos animais de laboratório, garantindo assim a qualidade e reprodutibilidade de experimentos com benefícios éticos, científicos e econômicos. Nos países da Europa e nos Estados Unidos, e requerido mais recentemente pelo Conselho Nacional de Controle de Experimentação Animal (CONCEA) no Brasil, um veterinário com experiência em medicina de animais de laboratório prec...

Research paper thumbnail of Quality of Adherence to the ARRIVE Guidelines in the Material and Methods Section in Studies Where Swine Were Used as Surgical Biomodels: A Systematic Review (2013–2018)

Animals

Over the last two decades, pigs have become animal biomodels widely used for the investigation an... more Over the last two decades, pigs have become animal biomodels widely used for the investigation and practice of surgical techniques because of their great physiological and anatomical similarities to humans. Even though many of these studies must be carried out later in humans, the description of basic information is limited, making exact repetitions of the reported experimental methods impossible. In this review, 108 studies from 2013 to 2018 were considered to determine the quality of adherence to the ARRIVE guidelines in the reports of the methodologies. The majority of the studies lacked the details recommended in the ARRIVE guidelines regarding data directly related to the welfare of animals undergoing surgery and those about anesthetic protocols and analgesics. Information related to sample size calculation and housing and husbandry conditions was also very limited. We believe that the ARRIVE guidelines are an excellent tool for good-quality reporting. We encourage scientists t...

Research paper thumbnail of Inhibitory effects of Euphorbia tirucalli latex on murine B16/F10 melanoma cells and lung metastasis

Molecular and Clinical Oncology

Euphorbia tirucalli (E. tirucalli) is a tropical and subtropical plant that produces a latex whic... more Euphorbia tirucalli (E. tirucalli) is a tropical and subtropical plant that produces a latex which is used for several purposes. The components of E. tirucalli latex include triterpenes, diterpenes and steroids. The aim of the present study was to evaluate the effects of diluted E. tirucalli latex on murine B16/F10 melanoma cells and lung metastasis. For this purpose, an in vitro study was first performed, in which B16/F10 cells were treated with diluted (1/2 to 1/11,192) E. tirucalli latex. In a second study, B16/F10 melanoma cells were inoculated into the tail vein of mice to generate lung metastases; the mice then received 0.467 µg of latex diluted in 200 ml saline by gavage for 14 days. A significant decrease in B16/F10 cell viability was observed using the MTT assay at 24 and 48 h after treatment with E. tirucalli latex. In addition, a significant decrease in the volume fraction occupied by B16/F10 metastatic colonies in the lungs was observed in mice treated with E. tirucalli latex. These results confirm the antineoplastic effects of diluted E. tirucalli latex.

Research paper thumbnail of Decontamination of genetically modified mice strains by embryo transfer for obtaining SPF colonies in a Brazilian animal facility

Brazilian Journal of Veterinary Research and Animal Science

The introduction of new strains of mice in specific pathogen-free (SPF) animal facilities should ... more The introduction of new strains of mice in specific pathogen-free (SPF) animal facilities should be performed carefully to avoid breaking sanitary barriers. To meet this need, animals should be rederived to reduce infection risk and thus avoid research interference caused by loss of animal health status and welfare. The objective of this study was to implement mice embryo transfer in the laboratory mouse facility of the Department of Immunology at the Institute of Biomedical Sciences/University of São Paulo, Brazil. Embryo transfers were performed to rederive genetically modified mouse strains with undefined sanitary status, received from different research and educational institutions. Fertilized eggs at two-cell stage were obtained by natural means and transferred into the oviducts of SPF pseudo-pregnant female mice. All surgical procedures were performed under aseptic conditions. A total of 625 embryos were transferred into therecipients. 148 pups were born, of which 140 were rea...

Research paper thumbnail of Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization

Research paper thumbnail of Genetic and behavioral characterization of a Kmt2d mouse mutant, a new model for Kabuki Syndrome

Genes, Brain and Behavior

Research paper thumbnail of Abstract 819: Transcriptomic profiling of two canine mammary cancer cell lines for translational oncology studies

Research paper thumbnail of A rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant

Archives of Virology

Rabies is one of the most important zoonotic diseases and is caused by several rabies virus (RABV... more Rabies is one of the most important zoonotic diseases and is caused by several rabies virus (RABV) variants. These variants can exhibit differences in neurovirulence, and few studies have attempted to evaluate the neuroinvasiveness of variants derived from vampire bats and wild carnivores. The aim of this study was to evaluate the neuropathogenesis of infection with two Brazilian RABV street variants (variant 3 and crab-eating fox) in mice. BALB/c mice were inoculated with RABV through the footpad, with the 50% mouse lethal dose (LD50) determined by intracranial inoculation. The morbidity of rabies in mice infected with variant 3 and the crab-eating fox strain was 100% and 50%, respectively, with an incubation period of 7 and 6 days post-inoculation (dpi), respectively. The clinical disease in mice was similar with both strains, and it was characterized initially by weight loss, ruffled fur, hunched posture, and hind limb paralysis progressing to quadriplegia and recumbency at 9 to 12 dpi. Histological lesions within the central nervous system (CNS) characterized by nonsuppurative encephalomyelitis with neuronal degeneration and necrosis were observed in mice infected with variant 3 and those infected with the crab-eating fox variant. However, lesions and the presence of RABV antigen, were more widespread within the CNS of variant-3-infected mice, whereas in crab-eating fox-variant-infected mice, RABV antigens were more restricted to caudal areas of the CNS, such as the spinal cord and brainstem. In conclusion, the results shown here demonstrate that the RABV vampire bat strain (variant 3) has a higher potential for neuroinvasiveness than the carnivore variant.

Research paper thumbnail of Experimental infestation of Gallus gallus with Ornithodoros (Alectorobius) amblus (Ixodoidea: Argasidae)

Journal of medical entomology, 1997

Ornithodoros (Alectorobius) amblus Chamberlin 1920 specimens were collected from a seagull (Larus... more Ornithodoros (Alectorobius) amblus Chamberlin 1920 specimens were collected from a seagull (Larus spp.) nest in northern Chile. This reports the occurrence of this species outside Peru. The biology of 79 specimens reared under laboratory conditions at 27 degrees C, 75-80% RH, and total darkness was determined. A 13% mortality rate from larval to adult was observed. Larval ticks were fed on chicks, Gallus gallus domesticus; and nymphs and adults were fed on chickens. We recorded the number of eggs per female per gonotrophic cycle and the mean duration of the periods of preoviposition, oviposition, and incubation. The total duration of their life cycle ranged from 111 to 239 d, depending on the number of molts. Males were found after the 4th molt, and after the 5th molt the proportion of females was greater than that of males or remaining nymphs. The feeding period of larvae was 4-6 d, N1 nymphs do not feed. The N2-N6 nymphs, males and females, had a 10- to 60-min feeding period. From...

Research paper thumbnail of Avaliação da etiopagenia da encefalite causada pelo herpesvírus equino tipo 1 utilizando um modelo murino de neuroinfecção

pela orientação, amizade e confiança. À Profa. Dra. Silvana Gorniak, minha segunda orientadora, p... more pela orientação, amizade e confiança. À Profa. Dra. Silvana Gorniak, minha segunda orientadora, pela amizade, incentivo e por ter abraçado a causa de produzir modelos animais com qualidade para a pesquisa. Ao Instituto Biológico de São Paulo, em nome das pesquisadoras Elenice M. S. Cunha, Maria do Carmo C. S. H. Lara e Eliana M.C.Villalobos pela valiosa colaboração em todas as etapas deste trabalho e pela oportunidade de realizar parte dos experimentos no Laboratório de Raiva e Encefalites. Aos professores do Departamento de Patologia Maria Lúcia Zaidan Dagli, Luciano Freitas Felício, Helenice Souza Spinosa e João Palermo Neto pelos ensinamentos transmitidos, incentivo e apoio durante todos esses anos de convívio e pela oportunidade da realização deste trabalho.

Research paper thumbnail of Detecção do DNA do herpesvírus eqüino 1 pela reação em cadeia pela polimerase em cavalos inoculados com a estirpe brasileira A4/72

Brazilian Journal of Veterinary Research and Animal Science, 2009

Research paper thumbnail of Altered expression of connexins in urethane-induced mouse lung adenomas

Life Sciences, Feb 11, 2006

Lung carcinogenesis is a multistep process whose molecular alterations can be studied in mouse mo... more Lung carcinogenesis is a multistep process whose molecular alterations can be studied in mouse models. Urethane, a specific lung tumor carcinogen, can induce adenomas in mice. Mouse lung alveolar cells reportedly generate lung neoplasms, and express connexins 26, 32, 43 and 46. The aim of the present study was to evaluate the expression of connexins in urethane-induced lung adenomas. Fifteen-day-old CD1 male mice received 2 i.p. injections of urethane (1.5 g/kg bw). The mice were euthanized 25 weeks after urethane injection, and lung adenomas were quantified. Lung tissue and lung adenomas were harvested and the RNA was extracted. The expression of connexins 26, 32, 43 and 46 was evaluated by Real-Time PCR, and these proteins were identified by Western blot. Immunohistochemistry revealed the distribution pattern of these connexins in lung tissue and adenomas. The treatment with urethane was associated with the downregulation of Cx26, 32 and 46 expressions, and with the upregulation of Cx43 expression in lung tissue. Surprisingly, in lung adenomas Cx32 and Cx43 expressions were not detected, although the expression of connexins 26 and 46 was present. Western blot and immunohistochemistry corroborated the RT-PCR data. These results may indicate a role of Cx32 and Cx43 in urethane-induced lung carcinogenesis, since their absence may contribute to the development of urethane induced lung tumors. The role of Cx26 and Cx46 is yet to be determined.

Research paper thumbnail of Molecular characterization of Brazilian equid herpesvirus type 1 strains based on neuropathogenicity markers

Brazilian Journal of Microbiology, 2015

Partial nucleotide sequences of ORF72 (glycoprotein D, gD), ORF64 (infected cell protein 4, ICP4)... more Partial nucleotide sequences of ORF72 (glycoprotein D, gD), ORF64 (infected cell protein 4, ICP4) and ORF30 (DNA polymerase) genes were compared with corresponding sequences of EHV-1 reference strains to characterize the molecular variability of Brazilian strains. Virus isolation assays were applied to 74 samples including visceral tissue, total blood, cerebrospinal fluid (CSF) and nasal swabs of specimens from a total of 64 animals. Only one CSF sample (Iso07/05 strain) was positive by virus isolation in cell culture. EHV-1 Iso07/05 neurologic strain and two abortion visceral tissues samples (Iso11/06 and Iso33/06) were PCR-positive for ORF33 (glycoprotein B, gB) gene of EHV-1. A sequence analysis of the ORF72, ORF64 and ORF30 genes from three EHV-1 archival strains (A3/97, A4/72, A9/92) and three clinical samples (Iso07/05, Iso11/06 and Iso33/06) suggested that among Brazilian EHV-1 strains, the amplified region of the gD gene sequence is highly conserved. Additionally, the analysis of ICP4 gene showed high nucleotide and amino acid identities when compared with genotype P strains, suggesting that the EHV-1 Brazilian strains belonged to the same group. All the EHV-1 Brazilian strains were classified as non-neuropathogenic variants (N752) based on the ORF30 analysis. These findings indicate a high conservation of the gD-, ICP4- and ORF30-encoding sequences. Different pathotypes of the EHV-1 strain might share identical genes with no specific markers, and tissue tropism is not completely dependent on the gD envelope, immediate-early ICP4 and DNA polymerase proteins.

Research paper thumbnail of Altered expression of connexins in urethane-induced mouse lung adenomas

Life Sciences, 2006

Lung carcinogenesis is a multistep process whose molecular alterations can be studied in mouse mo... more Lung carcinogenesis is a multistep process whose molecular alterations can be studied in mouse models. Urethane, a specific lung tumor carcinogen, can induce adenomas in mice. Mouse lung alveolar cells reportedly generate lung neoplasms, and express connexins 26, 32, 43 and 46. The aim of the present study was to evaluate the expression of connexins in urethane-induced lung adenomas. Fifteen-day-old CD1 male mice received 2 i.p. injections of urethane (1.5 g/kg bw). The mice were euthanized 25 weeks after urethane injection, and lung adenomas were quantified. Lung tissue and lung adenomas were harvested and the RNA was extracted. The expression of connexins 26, 32, 43 and 46 was evaluated by Real-Time PCR, and these proteins were identified by Western blot. Immunohistochemistry revealed the distribution pattern of these connexins in lung tissue and adenomas. The treatment with urethane was associated with the downregulation of Cx26, 32 and 46 expressions, and with the upregulation of Cx43 expression in lung tissue. Surprisingly, in lung adenomas Cx32 and Cx43 expressions were not detected, although the expression of connexins 26 and 46 was present. Western blot and immunohistochemistry corroborated the RT-PCR data. These results may indicate a role of Cx32 and Cx43 in urethane-induced lung carcinogenesis, since their absence may contribute to the development of urethane induced lung tumors. The role of Cx26 and Cx46 is yet to be determined.