Antifungal activity of linalool against fluconazole-resistant clinical strains of vulvovaginal Candida albicans and its predictive mechanism of action.

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.

Antifungal activity of linalool against fluconazole-resistant clinical strains of vulvovaginal Candida albicans and its predictive mechanism of action

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.

Systolic dysfunction by two-dimensional speckle tracking echocardiography in dogs with parvoviral enteritis.

INTRODUCTION/OBJECTIVES: Parvoviral enteritis (PVE) can cause either primary or secondary myocardial injury; the latter is associated with systemic inflammatory response syndrome and sepsis. Strain (St) and strain rate (SR) are relatively new speckle tracking echocardiographic (STE) variables used to assess myocardial function and are less influenced by preload and volume status than are conventional variables. The aim of this study was to evaluate systolic function in dogs with PVE using two-dimensional STE. ANIMALS: Forty-five client-owned dogs were included. MATERIALS AND METHODS: Dogs were classified into four groups: healthy (n = 9), PVE-mild (n = 15), PVE-severe (n = 13) and PVE-died (n = 8). Left ventricular global and segmental myocardial St and SR were assessed in radial, circumferential and longitudinal axes in the right parasternal transverse and apical 4-chamber views. In the circumferential and longitudinal axes, the value of each segment was determined separately at the endocardial and epicardial levels. RESULTS: Compared to healthy animals, all dogs with PVE showed significantly impaired St and SR values, mainly for PVE-severe and PVE-died groups. Moreover, the lowest SR value was observed in the circumferential axis at the mid-septal epicardial segment in the PVE-died group. For this variable, a cut-off value of 0.95 s-1 demonstrated 100% sensitivity and specificity for distinguishing between PVE-severe and PVE-died groups. CONCLUSIONS: In the present study, all dogs with PVE developed systolic dysfunction, which was more severe in non-survivors. Assessment of St and SR in dogs with PVE might be clinically useful for evaluating haemodynamic status and developing suitable therapeutic strategies to improve prognosis.

Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice.

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.

Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice

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.

Use of discriminant analysis based on echocardiography for classification of congestive heart failure in dogs with myxomatous mitral valve disease / Utilização da análise discriminante baseada na ecocardiografia para classificação de insuficiência cardíaca congestiva em cães com degeneração mixomatosa da valva mitral

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.

Use of discriminant analysis based on echocardiography for classification of congestive heart failure in dogs with myxomatous mitral valve disease / Utilização da análise discriminante baseada na ecocardiografia para classificação de insuficiência cardíaca congestiva em cães com degeneração mixomatosa da valva mitral

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...

Mitral flow propagation velocity in non-sedated healthy cats / Velocidade de propagação do fluxo mitral em gatos saudáveis e não sedados

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.

Longitudinal strain and strain rate by two-dimensional speckle tracking in non-sedated healthy cats.

Two dimensional speckle tracking (2D-ST) is a relatively new tool that has been used in veterinary medicine to quantify myocardial function. However, there is little information about the use of this tool in healthy cats. Thus, the aim of this study was to evaluate left ventricular longitudinal strain and strain rate in non-sedated healthy cats, as well as longitudinal velocity and displacement, by means of 2D-ST echocardiography. Thirty non-sedated healthy cats were examined and 2D images were obtained for 2D-ST analyzes. The global mean strain and strain rate was -15.65 ± 5.46% and -1.80 ± 0.59 s(-1), respectively. Velocity and displacement were 1.41 ± 0.87 cm/s and 1.27 ± 0.80 mm, respectively. Thus, 2D-ST demonstrated to be feasible for measuring left ventricular longitudinal strain, strain rate, velocity and displacement in cats and preliminary reference values for non-sedated healthy cats can be established from the results of this study.

Muscular arterial impedance in dogs with chronic degenerative mitral valve disease.

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.

Effects of sedation with acepromazine maleate and buprenorphine hydrochloride on femoral artery blood flow in healthy dogs.

The purpose of this study was to qualify and quantify the femoral artery blood flow by duplex Doppler ultrasonography (DDU) in healthy dogs, before and after the administration of a combination of acepromazine maleate and buprenorphine hydrochloride (ACP-BPN). Seven healthy adult mongrel dogs and three adult beagles were used. Heart rate, arterial blood pressure and measurement of femoral artery blood flow by DDU were also recorded. The DDU measurements were: femoral artery diameter (FAD), peak systolic velocity (PSV), early retrograde (EDV) and end diastolic velocities (EnDV), mean velocity (BMV), pulsatility index (PI), flow velocity integral (FVI) and femoral blood flow (FBF). After 30 min, combination ACP-BPN was administered intramuscularly, and all the measurements were recorded again. The ACP-BPN protocol induced a significant decrease in systolic, mean, and diastolic arterial blood pressure, and heart rate. A significant increase in peak systolic velocity and integral flow velocity integral of the femoral blood were obtained. The Doppler spectra of the blood flow in the femoral artery revealed a spectral dispersion pattern after ACP-BPN administration in all the dogs. These results demonstrate that despite quantitative and qualitative changes, the overall femoral blood flow (FBF) is not significantly modified.

Avaliação por eletrocardiografia contínua (holter) em cães da raça Pastor Alemão praticantes de atividade física regular / Ambulatory electrocardiography (Holter) evaluation in physically active German shepherd dogs

The pattern for ambulatory electrocardiography was evaluated in 25 healthy German Shepherd dogs. The influences of gender, age, and physical activity in HR maximum, mean, and minimum (HRmx, HRme, and HRmin, respectively) were studied. The physically active dogs (PA) showed lower HRme than sedentary animals (S) (P=0.03), whereas HRmx and HRmin were not altered (P=0.06 and P=0.65, respectively). The HRme was 80.89±13.85 for PA and 112.94±35.71 for S. No effect of gender and age on HR was observed. It is possible to state that the physical activity can modulate the sinus node of the dogs.

Fibrilação atrial em cão associada ao quimiodectoma infiltrativo atrial: relato de caso / Atrial fibrillation in dog associated with an infiltrative chemodectoma in the atrial myocardium: a case report

Relata-se o caso de um cão, sem raça definida, levado ao veterinário por apresentar cansaço fácil e episódios de síncope. Foram identificadas fibrilação atrial e extra-sístoles ventriculares isoladas ao exame eletrocardiográfico. O tratamento antiarrítmico não foi eficaz, e o animal morreu devido a um episódio de síncope. A necropsia, observou-se massa em região de base cardíaca, invadindo a luz do átrio esquerdo. Histologicamente, constatou-se a presença de quimiodectoma. A infiltração miocárdica atrial causou lesões nos miócitos, produzindo circuitos reentrantes e/ou focos ectópicos de despolarização atrial.

This case reports a mongrel dog referred to a veterinarian due to tiredness and syncope episodes. Atrial fibrillation and ventricular premature complex were observed during electrocardiographic exam. The anti-arrhythmic treatment was not effective and the dog died from syncope. At necropsy, a mass invading the internal area of the left atrium was evidenced in the base of the heart. The occurrence of chemodectoma was histologically exhibited. Infiltrations in the atrial myocardium caused alterations in the miocites and produced reentrant circuits and/or atrial depolarization ectopic points.

Avaliação do ritmo cardíaco em cães da raça Boxer saudáveis pela eletrocardiografia contínua ( Holter ) / Evaluation of the cardiac rhythm in healthy dogs of the Boxer breed using ambulatorial electrocardiography ( Holter )

The cardiac rhythm in a 24-hour period of 12 dogs of the Boxer breed, clinically healthy, males and females, of different ages was evaluated. No differences between males and females in the minimum, medium and maximum cardiac rates were observed (P>0.05). The females showed larger number of ventricular premature complex than the males. The major disorder in the cardiac rhythm was the ventricular premature complex. Several dogs showed the R over T phenomenon. Episodes of ventricular bigeminy and trigeminy were also observed.

Diagnóstico ecodopplercardiográfico da fibrose crônica da válvula mitral em cäo / Echodopplercardiographic diagnostic of mitral chronic valvular fibrosis in dog

A ten year-old male Poodle dog, weighing 3 kg, was referred to the Veterinary Hospital of UFMG due to nocturnal coughing, exercise intolerance, weakness and weight loss. Physical examination revealed pale mucous membranes, prolonged capillary refill time, holosystolic regurgitant murmur at left apex and signs of congestive heart failure. M-mode, two-dimensional, and Doppler echocardiography revealed mitral chronic valvular disease