RESUMO

Candida albicans is the most frequently isolated opportunistic pathogen in the female genital tract, with 92.3% of cases in Brazil associated with vulvovaginal candidiasis (VVC). Linalool is a monoterpene compound from plants of the genera Cinnamomum, Coriandrum, Lavandula, and Citrus that has demonstrated a fungicidal effect on strains of Candida spp., but its mechanism of action is still unknown. For this purpose, broth microdilution techniques were applied, as well as molecular docking in a predictive manner for this mechanism. The main results of this study indicated that the C. albicans strains analyzed were resistant to fluconazole and sensitive to linalool at a dose of 256 µg/mL. Furthermore, the increase in the minimum inhibitory concentration (MIC) of linalool in the presence of sorbitol and ergosterol indicated that this molecule possibly affects the cell wall and plasma membrane integrity of C. albicans. Molecular docking of linalool with proteins that are key in the biosynthesis and maintenance of the cell wall and the fungal plasma membrane integrity demonstrated the possibility of linalool interacting with three important enzymes: 1,3-ß-glucan synthase, lanosterol 14α-demethylase, and Δ 14-sterol reductase. In silico analysis showed that this monoterpene has theoretical but significant oral bioavailability, low toxic potential, and high similarity to pharmaceuticals. Therefore, the findings of this study indicated that linalool probably causes damage to the cell wall and plasma membrane of C. albicans, possibly by interaction with important enzymes involved in the biosynthesis of these fungal structures, in addition to presenting low in silico toxic potential.

Assuntos

RESUMO

Candida albicans is the most frequently isolated opportunistic pathogen in the female genital tract, with 92.3% of cases in Brazil associated with vulvovaginal candidiasis (VVC). Linalool is a monoterpene compound from plants of the genera Cinnamomum, Coriandrum, Lavandula, and Citrus that has demonstrated a fungicidal effect on strains of Candida spp., but its mechanism of action is still unknown. For this purpose, broth microdilution techniques were applied, as well as molecular docking in a predictive manner for this mechanism. The main results of this study indicated that the C. albicans strains analyzed were resistant to fluconazole and sensitive to linalool at a dose of 256 µg/mL. Furthermore, the increase in the minimum inhibitory concentration (MIC) of linalool in the presence of sorbitol and ergosterol indicated that this molecule possibly affects the cell wall and plasma membrane integrity of C. albicans. Molecular docking of linalool with proteins that are key in the biosynthesis and maintenance of the cell wall and the fungal plasma membrane integrity demonstrated the possibility of linalool interacting with three important enzymes: 1,3-β-glucan synthase, lanosterol 14α-demethylase, and Δ 14-sterol reductase. In silico analysis showed that this monoterpene has theoretical but significant oral bioavailability, low toxic potential, and high similarity to pharmaceuticals. Therefore, the findings of this study indicated that linalool probably causes damage to the cell wall and plasma membrane of C. albicans, possibly by interaction with important enzymes involved in the biosynthesis of these fungal structures, in addition to presenting low in silico toxic potential.

RESUMO

Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.

Assuntos

RESUMO

Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.

Assuntos

RESUMO

Mixomatous mitral valve disease (MMVD) is one of the most common cardiac abnormalities in dogs and humans that can lead to cardiac heart failure (CHF). Its diagnosis remains based on echocardiography and clinical signs. However, the early diagnose of MMVD can contribute to a better prognosis and avoid CHF. The aim of this study was to evaluate the clinical, radiographic and echocardiographic presence of CHF in dogs with MMVD in combination with a statistical model as a mathematical tool. For this purpose, dogs were divided into three groups (healthy; MMVD without CHF; and MMVD with CHF), according the clinical, radiographic and echocardiographic evaluation findings. Thus, linear discriminant functions were obtained by analyzing the variables weight, body surface area, aortic diameter, the ratio of the left atrium/aortic diameter, the ratio between the mitral regurgitation jet area and the left atrial area, vena contracta diameter and mitral valve proximal isovelocity surface area. Then, mathematical equations were established for each group of dogs. Statistical functions obtained in this study enabled to classify the dogs, regarding the presence of CHF with a probability of correct classification of 90.4%. Thus the statistical model demonstrated that it could be used as an auxiliary method for identifying CHF in dogs with MMVD.(AU)

A doença mixomatosa da valva mitral (DMVM) é uma das alterações cardíacas mais comuns em cães e humanos, a qual pode levar à insuficiência cardíaca congestiva (ICC). O diagnóstico dessa alteração ocorre com base principalmente no exame ecocardiográfico e na presença de sinais clínicos. No entanto, o diagnóstico precoce da DMVM pode contribuir para um melhor prognóstico e evitar o desenvolvimento de ICC. Assim, o objetivo do presente estudo foi avaliar a presença de ICC em cães com DMVM, por meio de exames clínico, radiográfico e ecocardiográfico em combinação com um modelo estatístico. Para este propósito, os cães foram divididos em três grupos (sadios; DMVM sem ICC; e DMVM com ICC), de acordo com os achados dos exames realizados. Então, as funções lineares discriminantes foram obtidas por meio da análise das variáveis peso; superfície de área corporal; diâmetro aórtico; relação entre o diâmetro do átrio esquerdo e aórtico; relação entre a área do jato regurgitante mitral e a área do átrio esquerdo; diâmetro da vena contracta e área da isovelocidade proximal mitral (PISA). As equações matemáticas foram estabelecidas para cada grupo de cães e demonstraram ser possível classificar os animais de acordo com a presença de ICC, com uma probabilidade de classificação correta de 90,4%. Diante disso, o modelo estatístico poderia ser uma ferramenta auxiliar para a identificação de ICC em cães com DMVM.(AU)

Assuntos

RESUMO

Mixomatous mitral valve disease (MMVD) is one of the most common cardiac abnormalities in dogs and humans that can lead to cardiac heart failure (CHF). Its diagnosis remains based on echocardiography and clinical signs. However, the early diagnose of MMVD can contribute to a better prognosis and avoid CHF. The aim of this study was to evaluate the clinical, radiographic and echocardiographic presence of CHF in dogs with MMVD in combination with a statistical model as a mathematical tool. For this purpose, dogs were divided into three groups (healthy; MMVD without CHF; and MMVD with CHF), according the clinical, radiographic and echocardiographic evaluation findings. Thus, linear discriminant functions were obtained by analyzing the variables weight, body surface area, aortic diameter, the ratio of the left atrium/aortic diameter, the ratio between the mitral regurgitation jet area and the left atrial area, vena contracta diameter and mitral valve proximal isovelocity surface area. Then, mathematical equations were established for each group of dogs. Statistical functions obtained in this study enabled to classify the dogs, regarding the presence of CHF with a probability of correct classification of 90.4%. Thus the statistical model demonstrated that it could be used as an auxiliary method for identifying CHF in dogs with MMVD...

A doença mixomatosa da valva mitral (DMVM) é uma das alterações cardíacas mais comuns em cães e humanos, a qual pode levar à insuficiência cardíaca congestiva (ICC). O diagnóstico dessa alteração ocorre com base principalmente no exame ecocardiográfico e na presença de sinais clínicos. No entanto, o diagnóstico precoce da DMVM pode contribuir para um melhor prognóstico e evitar o desenvolvimento de ICC. Assim, o objetivo do presente estudo foi avaliar a presença de ICC em cães com DMVM, por meio de exames clínico, radiográfico e ecocardiográfico em combinação com um modelo estatístico. Para este propósito, os cães foram divididos em três grupos (sadios; DMVM sem ICC; e DMVM com ICC), de acordo com os achados dos exames realizados. Então, as funções lineares discriminantes foram obtidas por meio da análise das variáveis peso; superfície de área corporal; diâmetro aórtico; relação entre o diâmetro do átrio esquerdo e aórtico; relação entre a área do jato regurgitante mitral e a área do átrio esquerdo; diâmetro da vena contracta e área da isovelocidade proximal mitral (PISA). As equações matemáticas foram estabelecidas para cada grupo de cães e demonstraram ser possível classificar os animais de acordo com a presença de ICC, com uma probabilidade de classificação correta de 90,4%. Diante disso, o modelo estatístico poderia ser uma ferramenta auxiliar para a identificação de ICC em cães com DMVM...

Assuntos

RESUMO

Mixomatous mitral valve disease (MMVD) is one of the most common cardiac abnormalities in dogs and humans that can lead to cardiac heart failure (CHF). Its diagnosis remains based on echocardiography and clinical signs. However, the early diagnose of MMVD can contribute to a better prognosis and avoid CHF. The aim of this study was to evaluate the clinical, radiographic and echocardiographic presence of CHF in dogs with MMVD in combination with a statistical model as a mathematical tool. For this purpose, dogs were divided into three groups (healthy; MMVD without CHF; and MMVD with CHF), according the clinical, radiographic and echocardiographic evaluation findings. Thus, linear discriminant functions were obtained by analyzing the variables weight, body surface area, aortic diameter, the ratio of the left atrium/aortic diameter, the ratio between the mitral regurgitation jet area and the left atrial area, vena contracta diameter and mitral valve proximal isovelocity surface area. Then, mathematical equations were established for each group of dogs. Statistical functions obtained in this study enabled to classify the dogs, regarding the presence of CHF with a probability of correct classification of 90.4%. Thus the statistical model demonstrated that it could be used as an auxiliary method for identifying CHF in dogs with MMVD.

A doença mixomatosa da valva mitral (DMVM) é uma das alterações cardíacas mais comuns em cães e humanos, a qual pode levar à insuficiência cardíaca congestiva (ICC). O diagnóstico dessa alteração ocorre com base principalmente no exame ecocardiográfico e na presença de sinais clínicos. No entanto, o diagnóstico precoce da DMVM pode contribuir para um melhor prognóstico e evitar o desenvolvimento de ICC. Assim, o objetivo do presente estudo foi avaliar a presença de ICC em cães com DMVM, por meio de exames clínico, radiográfico e ecocardiográfico em combinação com um modelo estatístico. Para este propósito, os cães foram divididos em três grupos (sadios; DMVM sem ICC; e DMVM com ICC), de acordo com os achados dos exames realizados. Então, as funções lineares discriminantes foram obtidas por meio da análise das variáveis peso; superfície de área corporal; diâmetro aórtico; relação entre o diâmetro do átrio esquerdo e aórtico; relação entre a área do jato regurgitante mitral e a área do átrio esquerdo; diâmetro da vena contracta e área da isovelocidade proximal mitral (PISA). As equações matemáticas foram estabelecidas para cada grupo de cães e demonstraram ser possível classificar os animais de acordo com a presença de ICC, com uma probabilidade de classificação correta de 90,4%. Diante disso, o modelo estatístico poderia ser uma ferramenta auxiliar para a identificação de ICC em cães com DMVM.

Assuntos

RESUMO

Mitral flow propagation velocity (Vp) is an index used to evaluate the left ventricular diastolic function. Its influence on human and small animal cardiopathies has been studied; however there are few reports evaluating this variable in domestic felines. In addition, there is a lack of studies in non-sedated healthy cats. Therefore, the purpose of this study was to establish values for Vp and its correlation with other echocardiographic indexes in non-sedated healthy cats in order to provide new perspectives related to diastolic function in this species. Twenty-six clinically healthy cats were submitted to echocardiography to assess the animals' cardiac conditions. Variables such as age, heart rate (HR), body surface area (BSA), initial (E mitral) and late (A mitral) ventricular filling waves, isovolumic relaxation time (IVRT) and E/IVRT relation were correlated to Vp. No proven relation between any of these variables and Vp was observed in this present study, except for HR and BSA. In the variability analysis, higher values were verified for inter-observer analysis. This study concludes that Vp proved to be an useful index for estimating left ventricular relaxation in non-sedated healthy domestic cats and provides reference ranges for this variable.(AU)

A velocidade de propagação do fluxo mitral (Vp) é um índice utilizado para avaliação da função diastólica do ventrículo esquerdo. Sua importância nas cardiopatias em humanos e pequenos animais vem sendo estudada; porém, há poucos trabalhos avaliando essa variável em gatos domésticos. Nessa espécie, estudos utilizando animais saudáveis e não sedados não foram encontrados na literatura. Dessa forma, objetivou-se estabelecer os valores da Vp e sua correlação com outros índices ecocardiográficos em gatos domésticos saudáveis e não sedados, de forma a fornecer novas perspectivas relacionadas à função diastólica nessa espécie. Foram utilizados 26 gatos domésticos clinicamente saudáveis, submetidos à ecocardiografia para se avaliar a condição cardíaca dos animais. As variáveis idade, frequência cardíaca (FC), área de superfície corporal (SAC), idade, onda de enchimento ventricular inicial (E mitral) e tardio (A mitral), tempo de relaxamento isovolumétrico (TRIV) e a relação E/TRIV foram correlacionadas com a Vp. No presente estudo não foi observada correlação da Vp com nenhuma das variáveis estudas, exceto com a FC e o SAC. Quanto à análise de variabilidade, foi observado um maior valor para a análise inter-observador. O estudo permite concluir que a Vp demonstrou ser um índice útil para se estimar o relaxamento ventricular esquerdo em gatos domésticos saudáveis e não sedados, além de fornecer valores de referência para essa variável.(AU)

Assuntos

RESUMO

Mitral flow propagation velocity (Vp) is an index used to evaluate the left ventricular diastolic function. Its influence on human and small animal cardiopathies has been studied; however there are few reports evaluating this variable in domestic felines. In addition, there is a lack of studies in non-sedated healthy cats. Therefore, the purpose of this study was to establish values for Vp and its correlation with other echocardiographic indexes in non-sedated healthy cats in order to provide new perspectives related to diastolic function in this species. Twenty-six clinically healthy cats were submitted to echocardiography to assess the animals' cardiac conditions. Variables such as age, heart rate (HR), body surface area (BSA), initial (E mitral) and late (A mitral) ventricular filling waves, isovolumic relaxation time (IVRT) and E/IVRT relation were correlated to Vp. No proven relation between any of these variables and Vp was observed in this present study, except for HR and BSA. In the variability analysis, higher values were verified for inter-observer analysis. This study concludes that Vp proved to be an useful index for estimating left ventricular relaxation in non-sedated healthy domestic cats and provides reference ranges for this variable.

A velocidade de propagação do fluxo mitral (Vp) é um índice utilizado para avaliação da função diastólica do ventrículo esquerdo. Sua importância nas cardiopatias em humanos e pequenos animais vem sendo estudada; porém, há poucos trabalhos avaliando essa variável em gatos domésticos. Nessa espécie, estudos utilizando animais saudáveis e não sedados não foram encontrados na literatura. Dessa forma, objetivou-se estabelecer os valores da Vp e sua correlação com outros índices ecocardiográficos em gatos domésticos saudáveis e não sedados, de forma a fornecer novas perspectivas relacionadas à função diastólica nessa espécie. Foram utilizados 26 gatos domésticos clinicamente saudáveis, submetidos à ecocardiografia para se avaliar a condição cardíaca dos animais. As variáveis idade, frequência cardíaca (FC), área de superfície corporal (SAC), idade, onda de enchimento ventricular inicial (E mitral) e tardio (A mitral), tempo de relaxamento isovolumétrico (TRIV) e a relação E/TRIV foram correlacionadas com a Vp. No presente estudo não foi observada correlação da Vp com nenhuma das variáveis estudas, exceto com a FC e o SAC. Quanto à análise de variabilidade, foi observado um maior valor para a análise inter-observador. O estudo permite concluir que a Vp demonstrou ser um índice útil para se estimar o relaxamento ventricular esquerdo em gatos domésticos saudáveis e não sedados, além de fornecer valores de referência para essa variável.

Assuntos

RESUMO

Systemic vascular impedance represents the retrograde strength of the blood flow to the left ventricle, thus it is one of the main compounds of afterload. Mitral regurgitation is markedly sensitive to afterload alterations. The purpose of this study was to evaluate muscular arterial impedance in dogs with chronic degenerative mitral valve disease (CDMVD) by use of duplex Doppler ultrasonography (DDU), since its technique there was not used before to determine impedance index in dogs with CDMVD. For this purpose, ten healthy dogs and ten dogs with CDMVD were used. Some parameters related to blood flow impedance in the common femoral artery were measured by DDU: pulsatility index (PI), resistance index (RI), high-resistance index (HRI), and acceleration velocity (AC) and deceleration velocity (DC) of the systolic peak. The results showed that RI and HRI were significantly higher in animals with CDMVD than in healthy animals. These findings showed that DDU provides quantitative data related to vascular impedance. Broader studies may therefore provide new aspects related to physiopathology and therapy in CDMVD patients.

Assuntos