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This study aimed to evaluate the corneal epitheliotoxic effects of preservative-free ketorolac tromethamine 0.5% and diclofenac sodium 0.1% eye drops in rabbits. Seventeen New Zealand rabbits were randomly divided into three groups: the 0.5% ketorolac tromethamine group, the 0.1% diclofenac sodium group, and the control group (0.9% NaCl). For each rabbit, both eyes were treated three times daily according to their treatment group. The corneal epithelia were analyzed using scanning electron microscopy to observe the number of light, grey, and dark cells; the number of epithelial holes; and the loss of hexagonal shape. Both of the formulations administered caused changes in the healthy corneal epithelia of rabbits. Except for number of epithelial holes (p < 0.05), all the parameters showed a statistically significant difference between the groups. The number of dark cells was highest in the ketorolac tromethamine group (p<0.05). The number of grey cells was higher in the diclofenac sodium group than in the control group (p =0.003). A higher number of dark cells was associated with a smaller number of light cells (r =-0.577, p < 0.001). Loss of shape showed a direct correlation with the number of dark cells (r=0.524, p=0.002). Based on the results presented, it was possible to conclude that ketorolac tromethamine 0.5% was more toxic to rabbit corneal epithelium than diclofenac sodium 0.1%.

Objetivou-se avaliar os efeitos do cetorolaco de trometamina a 0,5% e do diclofenaco de sódico a 0,1% sem conservantes na córnea de coelhos. Dezessete coelhos da raça Nova Zelândia foram aleatoriamente divididos em três grupos: o grupo de 0,5% de cetorolaco de trometamina, o grupo de 0,1% de diclofenaco sódico e o grupo controle (0,9% de NaCl). Para cada coelho, os dois olhos foram tratados três vezes ao dia durante 90 dias de acordo com o grupo de tratamento. Os epitélios da córnea foram analisados usando microscopia eletrônica de varredura para observar o número de células claras, cinzas e escuras, o número de criptas e a perda do formato celular hexagonal. Ambas as formulações administradas causaram alterações no epitélio da córnea de coelhos. Com exceção da contagem de criptas (p <0,05), todos os parâmetros apresentaram diferença estatisticamente significante entre os grupos. O número de células escuras foi maior no grupo cetorolaco de trometamina (p <0,05). O número de células cinzentas foi maior no grupo diclofenaco de sódio do que no grupo controle (p=0,003). O maior número de células escuras observado foi associado ao menor número de células claras (r=-0,577, p<0,001). A perda do formato celular mostrou uma correlação direta com o número de células escuras (r=0,524, p=0,002). O cetorolaco de trometamina 0,5% foi mais tóxico para o epitélio da córnea de coelhos do que o diclofenaco de sódio a 0,1%.

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Despite the increasing use of oregano (Origanum vulgare L.) essential oil for therapeutic purposes, pre- and postnatal development of animals offspring exposed to this oil has not yet been evaluated. In line with previous concerns of genotoxicity, in this study adult rats were exposed to different doses of oregano essential oil (3, 9 and 27% vol/vol) during pre-mating, mating, gestation and lactation. Prenatal screening included fetal development and uterine inspection, where the reproductive rate of females such as breeding, pregnancy, delivery, viability and post-implantation loss rate were measured. Postnatal evaluation of rat offspring included motor development, neuroendocrine and behavioral assessment. Body weight of rat dams and signs of dystocia were evaluated daily. Development of physic characteristics and reflex tests of puppies were also assessed. Additionally, these rats, when adults, were submitted to sexual and open field behavioral tests. The main differences among the groups were observed in the indices of mating, pregnancy and post-implantation loss (P < 0.01). Results demonstrated that the treatment of parental generation with oregano essential oil has the potential to affect the developing fetuses at the highest dose used, but without causing maternal toxicity and changes in general behavior and development of the progeny.

Apesar do aumento do uso do óleo essencial de orégano (Origanum vulgare L.) para fins terapêuticos, o desenvolvimento pré e pós-natal da progênie de animais expostos a este óleo ainda não foi avaliado. Partindo das suspeitas prévias de genotoxicidade desse óleo, neste estudo, ratos Wistar adultos foram expostos a diferentes doses do óleo essencial de orégano (3, 9 e 27% vol/vol) durante o acasalamento, a gestação e a lactação. Para a avaliação pré-natal, o desenvolvimento gestacional foi observado e os úteros inspecionados, assim como os índices reprodutivos das fêmeas, como a taxa de acasalamento, de gestação, parto e perdas pós-implantação. Na avaliação pós-natal, observou-se o desenvolvimento motor, neuroendócrino e comportamental da prole. Observou-se, diariamente, o peso das ratas e sinais de distocia. Após o parto, as características de desenvolvimento e testes de reflexos dos filhotes foram avaliadas, enquanto que, na puberdade, foram realizadas análises histopatológicas e dosagem hormonal. Adicionalmente, na idade adulta, esses ratos foram submetidos ao teste de comportamento em campo aberto e ao comportamento sexual. As principais diferenças entre os grupos foram nos índices de acasalamento, de gestação e de perdas pós-implantação (P < 0,01). Os resultados demonstram que o tratamento da geração parental com óleo essencial de orégano tem potencial para afetar os índices reprodutivos das ratas e o desenvolvimento dos fetos na maior dose utilizada, mas sem causar toxicidade materna e alterações no desenvolvimento geral e comportamental da sua progênie.

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Despite the increasing use of oregano (Origanum vulgare L.) essential oil for therapeutic purposes, pre- and postnatal development of animals offspring exposed to this oil has not yet been evaluated. In line with previous concerns of genotoxicity, in this study adult rats were exposed to different doses of oregano essential oil (3, 9 and 27% vol/vol) during pre-mating, mating, gestation and lactation. Prenatal screening included fetal development and uterine inspection, where the reproductive rate of females such as breeding, pregnancy, delivery, viability and post-implantation loss rate were measured. Postnatal evaluation of rat offspring included motor development, neuroendocrine and behavioral assessment. Body weight of rat dams and signs of dystocia were evaluated daily. Development of physic characteristics and reflex tests of puppies were also assessed. Additionally, these rats, when adults, were submitted to sexual and open field behavioral tests. The main differences among the groups were observed in the indices of mating, pregnancy and post-implantation loss (P < 0.01). Results demonstrated that the treatment of parental generation with oregano essential oil has the potential to affect the developing fetuses at the highest dose used, but without causing maternal toxicity and changes in general behavior and development of the progeny.(AU)

Apesar do aumento do uso do óleo essencial de orégano (Origanum vulgare L.) para fins terapêuticos, o desenvolvimento pré e pós-natal da progênie de animais expostos a este óleo ainda não foi avaliado. Partindo das suspeitas prévias de genotoxicidade desse óleo, neste estudo, ratos Wistar adultos foram expostos a diferentes doses do óleo essencial de orégano (3, 9 e 27% vol/vol) durante o acasalamento, a gestação e a lactação. Para a avaliação pré-natal, o desenvolvimento gestacional foi observado e os úteros inspecionados, assim como os índices reprodutivos das fêmeas, como a taxa de acasalamento, de gestação, parto e perdas pós-implantação. Na avaliação pós-natal, observou-se o desenvolvimento motor, neuroendócrino e comportamental da prole. Observou-se, diariamente, o peso das ratas e sinais de distocia. Após o parto, as características de desenvolvimento e testes de reflexos dos filhotes foram avaliadas, enquanto que, na puberdade, foram realizadas análises histopatológicas e dosagem hormonal. Adicionalmente, na idade adulta, esses ratos foram submetidos ao teste de comportamento em campo aberto e ao comportamento sexual. As principais diferenças entre os grupos foram nos índices de acasalamento, de gestação e de perdas pós-implantação (P < 0,01). Os resultados demonstram que o tratamento da geração parental com óleo essencial de orégano tem potencial para afetar os índices reprodutivos das ratas e o desenvolvimento dos fetos na maior dose utilizada, mas sem causar toxicidade materna e alterações no desenvolvimento geral e comportamental da sua progênie.(AU)

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Iobitridol is a tri-iodinated contrast agent, and neurotoxicologic studies of the intracisternal administration are scarce and inconclusive. The purpose of this study was to compare the neurotoxicity of iobitridol with iohexol, by intracisternal administration in Wistar rats, for a pre-clinical evaluation of its use as a myelographic agent. The animals, a total of 75, were divided into three experimental groups, iobitridol, iohexol and cerebral artificial fluid (control group), with 25 animals per group. Then, these were divided into five subgroups of five animals each, and given doses of 200, 400, 600, 800 and 1000 mg kg-1, while the control group received the equivalent volumes of contrast media tested. The animals were evaluated after 5, 15, 30, 60, 120, 180 and 240 min of intracisternal administration of these substances, for signs of depression and excitement, tactile palmar grasp, flexor, extensor, palpebral, papillary and pinna reflexes, surface righting and placing reactions, and with an auditory startle test. The evaluations were assessed daily for seven days with these parameters and their body weight, food, and water intake were also measured. There were no statistically significant differences between groups tested with respect to any of the evaluated parameters. In other words, in this animal model, the iobitridol demonstrated a low neurotoxicologic potential, comparable to that observed with iohexol. Further study with dogs and cats, as an alternative, is suggested.(AU)

O iobitridol é um meio de contraste tri-iodado, e estudos referentes à neurotoxicidade, com administração subaracnóide são escassos e inconclusivos. O objetivo deste trabalho foi comparar a neurotoxicidade do iobitridol com a do iohexol, por via intracisternal, em ratos Wistar, como avaliação pré-clínica da utilização deste como agente mielográfico. Foram utilizados 75 animais divididos em três grupos experimentais com 25 animais: iobitridol, iohexol e líquido cerebroespinhal artificial (grupo controle). Estes foram subdivididos em cinco subgrupos com cinco animais cada, com doses distintas de 200, 400, 600, 800 e 1000 mg kg-1, sendo utilizado no grupo controle o volume equivalente aos meios de contraste testados. Os animais foram avaliados após 5, 15, 30, 60, 120, 180 e 240 min da administração intracisternal dessas substâncias, quanto a sinais de depressão e excitação, reflexos tátil de agarramento palmar, flexor, extensor, palpebral, pupilar e da pina, reação de endireitamento e posicionamento e resposta auditiva. Nos sete dias subsequentes, os animais foram avaliados diariamente quanto a estes parâmetros, e ainda a massa corporal, a ingestão de ração e de água, foram mensuradas. Não foram observadas diferenças estatisticamente significativas entre os grupos testados com meios de contraste, em nenhum dos parâmetros avaliados. Dessa forma, nesse modelo animal, o iobitridol demonstrou baixa neurotoxicidade, comparável a observada com o iohexol. Sugerem-se mais estudos com cães e gatos para utilização do iobitridol como alternativa.(AU)

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RESUMO

Iobitridol is a tri-iodinated contrast agent, and neurotoxicologic studies of the intracisternal administration are scarce and inconclusive. The purpose of this study was to compare the neurotoxicity of iobitridol with iohexol, by intracisternal administration in Wistar rats, for a pre-clinical evaluation of its use as a myelographic agent. The animals, a total of 75, were divided into three experimental groups, iobitridol, iohexol and cerebral artificial fluid (control group), with 25 animals per group. Then, these were divided into five subgroups of five animals each, and given doses of 200, 400, 600, 800 and 1000 mg kg-1, while the control group received the equivalent volumes of contrast media tested. The animals were evaluated after 5, 15, 30, 60, 120, 180 and 240 min of intracisternal administration of these substances, for signs of depression and excitement, tactile palmar grasp, flexor, extensor, palpebral, papillary and pinna reflexes, surface righting and placing reactions, and with an auditory startle test. The evaluations were assessed daily for seven days with these parameters and their body weight, food, and water intake were also measured. There were no statistically significant differences between groups tested with respect to any of the evaluated parameters. In other words, in this animal model, the iobitridol demonstrated a low neurotoxicologic potential, comp

O iobitridol é um meio de contraste tri-iodado, e estudos referentes à neurotoxicidade, com administração subaracnóide são escassos e inconclusivos. O objetivo deste trabalho foi comparar a neurotoxicidade do iobitridol com a do iohexol, por via intracisternal, em ratos Wistar, como avaliação pré-clínica da utilização deste como agente mielográfico. Foram utilizados 75 animais divididos em três grupos experimentais com 25 animais: iobitridol, iohexol e líquido cerebroespinhal artificial (grupo controle). Estes foram subdivididos em cinco subgrupos com cinco animais cada, com doses distintas de 200, 400, 600, 800 e 1000 mg kg-1, sendo utilizado no grupo controle o volume equivalente aos meios de contraste testados. Os animais foram avaliados após 5, 15, 30, 60, 120, 180 e 240 min da administração intracisternal dessas substâncias, quanto a sinais de depressão e excitação, reflexos tátil de agarramento palmar, flexor, extensor, palpebral, pupilar e da pina, reação de endireitamento e posicionamento e resposta auditiva. Nos sete dias subsequentes, os animais foram avaliados diariamente quanto a estes parâmetros, e ainda a massa corporal, a ingestão de ração e de água, foram mensuradas. Não foram observadas diferenças estatisticamente significativas entre os grupos testados com meios de contraste, em nenhum dos parâmetros avaliados. Dessa forma, nesse modelo animal, o iobitridol de

RESUMO

Iobitridol is a tri-iodinated contrast agent, and neurotoxicologic studies of the intracisternal administration are scarce and inconclusive. The purpose of this study was to compare the neurotoxicity of iobitridol with iohexol, by intracisternal administration in Wistar rats, for a pre-clinical evaluation of its use as a myelographic agent. The animals, a total of 75, were divided into three experimental groups, iobitridol, iohexol and cerebral artificial fluid (control group), with 25 animals per group. Then, these were divided into five subgroups of five animals each, and given doses of 200, 400, 600, 800 and 1000 mg kg-1, while the control group received the equivalent volumes of contrast media tested. The animals were evaluated after 5, 15, 30, 60, 120, 180 and 240 min of intracisternal administration of these substances, for signs of depression and excitement, tactile palmar grasp, flexor, extensor, palpebral, papillary and pinna reflexes, surface righting and placing reactions, and with an auditory startle test. The evaluations were assessed daily for seven days with these parameters and their body weight, food, and water intake were also measured. There were no statistically significant differences between groups tested with respect to any of the evaluated parameters. In other words, in this animal model, the iobitridol demonstrated a low neurotoxicologic potential, comparable to that observed with iohexol. Further study with dogs and cats, as an alternative, is suggested.

O iobitridol é um meio de contraste tri-iodado, e estudos referentes à neurotoxicidade, com administração subaracnóide são escassos e inconclusivos. O objetivo deste trabalho foi comparar a neurotoxicidade do iobitridol com a do iohexol, por via intracisternal, em ratos Wistar, como avaliação pré-clínica da utilização deste como agente mielográfico. Foram utilizados 75 animais divididos em três grupos experimentais com 25 animais: iobitridol, iohexol e líquido cerebroespinhal artificial (grupo controle). Estes foram subdivididos em cinco subgrupos com cinco animais cada, com doses distintas de 200, 400, 600, 800 e 1000 mg kg-1, sendo utilizado no grupo controle o volume equivalente aos meios de contraste testados. Os animais foram avaliados após 5, 15, 30, 60, 120, 180 e 240 min da administração intracisternal dessas substâncias, quanto a sinais de depressão e excitação, reflexos tátil de agarramento palmar, flexor, extensor, palpebral, pupilar e da pina, reação de endireitamento e posicionamento e resposta auditiva. Nos sete dias subsequentes, os animais foram avaliados diariamente quanto a estes parâmetros, e ainda a massa corporal, a ingestão de ração e de água, foram mensuradas. Não foram observadas diferenças estatisticamente significativas entre os grupos testados com meios de contraste, em nenhum dos parâmetros avaliados. Dessa forma, nesse modelo animal, o iobitridol demonstrou baixa neurotoxicidade, comparável a observada com o iohexol. Sugerem-se mais estudos com cães e gatos para utilização do iobitridol como alternativa.

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Background: Doppler ultrasound is a non-invasive diagnostic imaging technique that allows vascular anatomical and dynamics evaluation. Each artery has flow velocity profiles and different Doppler spectrum. The purpose of this study was to determine if sedation with acepromazine and butorphanol in dogs alters Doppler velocimetric values and diameter from abdominal aorta, celiac, mesenteric cranial, renal, external iliac and femoral arteries of healthy dogs.Materials, Methods & Results: Twenty healthy female dogs, aged 1 to 5 years, with body weight ranging from 10 to 25 kg, were evaluated with Doppler ultrasound in order to obtain: peak systolic velocity, end diastolic velocity, time average medium velocity, time average maximum velocity, resistive index, pulsatility index, and diameter from abdominal aorta, celiac, mesenteric cranial, renal, external iliac and femoral arteries. The same animals were sedated with acepromazine (0.02 mg/kg) and buthorphanol (0.4 mg/kg) and the same parameters were reevaluated. The heart rate was also measured. The study was approved by the Animal Ethics Committee of UFRGS, under the 25552 protocol, and the owners signed an informed consent form. Statistical analysis was performed with pared t test.The heart rate was statistically significant different, 98 ± 20.13 bpm before and 79 ± 17.74 after sedation. The exam was done before and after [...](AU)

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Background: Doppler ultrasound is a non-invasive diagnostic imaging technique that allows vascular anatomical and dynamics evaluation. Each artery has flow velocity profiles and different Doppler spectrum. The purpose of this study was to determine if sedation with acepromazine and butorphanol in dogs alters Doppler velocimetric values and diameter from abdominal aorta, celiac, mesenteric cranial, renal, external iliac and femoral arteries of healthy dogs.Materials, Methods & Results: Twenty healthy female dogs, aged 1 to 5 years, with body weight ranging from 10 to 25 kg, were evaluated with Doppler ultrasound in order to obtain: peak systolic velocity, end diastolic velocity, time average medium velocity, time average maximum velocity, resistive index, pulsatility index, and diameter from abdominal aorta, celiac, mesenteric cranial, renal, external iliac and femoral arteries. The same animals were sedated with acepromazine (0.02 mg/kg) and buthorphanol (0.4 mg/kg) and the same parameters were reevaluated. The heart rate was also measured. The study was approved by the Animal Ethics Committee of UFRGS, under the 25552 protocol, and the owners signed an informed consent form. Statistical analysis was performed with pared t test.The heart rate was statistically significant different, 98 ± 20.13 bpm before and 79 ± 17.74 after sedation. The exam was done before and after [...]

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Background: The oregano essential oil (Origanum vulgare L.) is rich in phenolic compounds with therapeutic actionssuch as antimicrobial, antifungal and antioxidant. Based on the therapeutic potential and clinical use of oregano essentialoil, in vivo toxicology studies of oregano essential oil are scarce and the current researches focus on the genotoxicity ofseveral species of oregano; however, toxicological and complementary studies are needed to ensure safety of formulationscontaining this oil. Through values of Minimum Inhibitory Concentration (MIC) of oregano essential oil against Candidaspecies, and increased in an exponential scale, the initial dose was obtained. This study aims to evaluate male fertilitythrough the reproductive aspects of rats chronically treated with oregano essential oil.Materials, Methods & Results: The rats were divided into five groups with 10 males and 30 females each; three groupswere treated with oregano essential oil at a concentration of 3% Vol/Vol (GO3%), of 9% Vol/Vol (GO9%) and of 27% Vol/Vol (GO27%). The negative control group received the vehicle, 0.001% Vol/Vol Tween 80 (GC-) and the positive controlgroup was treated with thymol and terpinen-4-ol, at the same concentration found in the oregano essential oil, detected bygas chromatography (3% + 3% Vol/Vol) (GC+). Animals were allowed to adapt for at least ten days before the beginningof the experiment. They were maintained under...(AU)

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Background: Reports of yeast isolates resistant to traditional antifungal drugs have become common. Similarly, refractory clinical cases treated with these traditional antifungal drugs have also been reported. These cases ‘may or may not be related to pregnancy. Newly developed therapeutic approaches, such as the immunostimulant β-glucan combined with the traditional antifungal agents show promising results. Therefore, knowledge of the effects of these new associations is essential. The aims of this study were to evaluate the effects of the combination of itraconazole and β (1-3) glucan on fertility in female rats and its interference in the development of their offspring, including teratogenic potential.Materials, Methods & Results: A total of 180 female Wistar rats (90 days old) separated into six groups were used (n = 30 per group): Negative Control - treated daily with the volume corresponding to 10 mL.kg-1 of sterile distilled water orally, and 0.25 mL of sterile 0.9% NaCl solution subcutaneously weekly; IT - treated daily with itraconazole at a dose of 10 mg.kg-1 orally, and 0.25 ml of sterile 0.9% NaCl solution subcutaneously weekly; Beta - treated daily with the volume corresponding to 10 mL.kg-1 of sterile distilled water orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly; DT - treated daily with itraconazole at a dose of 10 mg.kg-1 orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly; DT5x - treated daily with itraconazole at a dose of 50 mg.kg-1 orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly; DT10x - treated daily with itraconazole at a dose of 100 mg.kg-1 orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly. The rats were treated before (14 days) and during the mating period (up to 21 days), pregnancy (21 days) and lactation (21 days).[...]

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