Multilobular tumor of bone in bitches: clinical, histopathological, immunohistochemical and overall survival aspects

Background: Multilobular tumor of bone (MTB) is an unusual neoplasm with variable biologic behavior which originates primarily in bone tissues. Radiographs computed tomography (CT), and magnetic resonance imaging (MRI) are useful in diagnoses and surgical planning. Tumor removal with wide surgical margins is the treatment of choice. Immunohistochemistry has been shown as an important tool in veterinary oncology to define therapeutic and prognostic decisions. The goal of this study was to report 2 distinct cases of multilobular tumor of bone, their Cox-2 and Mib-1 immunohistochemical profile and its impact on overall survival. Case: Two bitches were presented at the Oncology Department of the Veterinary Hospital in the Veterinary School of Universidade Federal de Minas Gerais (UFMG). Both had a history of a progressive, painless, circumscribed, and firm facial mass. The 1st patient was a 8-year-old intact bitch mixed breed, weighing 50 kg, that presented a fast growing right infraorbital 3-cm mass, causing eye displacement. The 2nd patient was a 7-year-old spayed bitch Labrador retriever, weighing 28 kg, that presented a left temporal 8-cm mass. Neurologic examination of both bitches was normal. Skin over the nodules was strained, but with no ulceration. Radiographic exams of the head revealed lytic and proliferative bone reaction, with loss of cortical definition in both cases. These alterations were seen on the left zygomatic arch of the retrobulbar region, involving part of the mandible and of the nasal sinus lateral frontal bone in 1st patient, and on the right temporal process of the zygomatic bone in 2nd patient. The last one, also showed a granular solid mass with little contact with skull bones. Complete blood count, biochemistry profile, electrocardiogram, and 3-view thoracic radiographs were performed. Results were within normal ranges for the species and no signs of metastasis was seen on the radiographs. Location, size, and density of the mass, adjacent tissue compression, absence of cranial invasion, and lymph node size were rigorously evaluated with CT, allowing an individualized surgical planning to achieve complete mass removal and maintenance of the function of adjacent structures. Both animals were submitted to surgery. Both tumors were fixed on 10% neutral buffered formalin and sent to the Animal Pathology Department of UFMG for histopathological examination and margin assessment. Both tumors were diagnosed as grade I MTB. Tumor immunohistochemistry was performed to identify prognostic factors that could be used to better define therapeutic treatments and to try to clarify the discrepancy in disease progression between both tumors. The 1st patient expressed 20% of Mib-1 and was considered score 2 of Cox-2. The 2nd one expressed 5% of Mib-1 and was considered score 1 of Cox-2. Considering the diagnoses and histological characteristics of the tumors, it was decided for clinical follow-up of patients without additional therapeutic complementation. Even considering incomplete surgical margins in 2nd patient, adjuvant chemotherapy was not performed, due to low mitotic index and low histological grade. The 1st patient had an overall survival of 240 days, and death was due to recurrence and disease progression; and the 2nd did not show recurrence nor metastasis after 1200 days. Discussion: Proper and individualized surgical planning and histopathological evaluation are extremely important to guide treatment decisions. However, immunohistochemistry can be important in MTB cases, to help define which patients should be submitted to surgery alone and which patients could be benefited from adjuvant chemotherapy.

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats

Abstract Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-B), tumor necrosis factor- (TNF-), Interleukin-1 (IL-1), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

Resumo A cisplatina (CP) é uma droga antineoplásica poderosa, comumente usada, com vários efeitos colaterais. Casticin (CAS) é considerado um eliminador de radicais livres e um potente antioxidante. A presente pesquisa foi planejada para avaliar o potencial curativo da CAS em lesão renal induzida por PC em ratos albinos machos. Vinte e quatro ratos albinos machos foram distribuídos em quatro grupos iguais. O Grupo 1 foi considerado grupo controle. Os animais do Grupo 2 foram injetados com 5 mg / kg de PB por via intraperitoneal. O Grupo 3 foi cotratado com CAS (50 mg / kg) por via oral e injeção de CP (5 mg / kg). O Grupo 4 foi tratado com CAS (50 mg / kg) por via oral durante todo o experimento. A administração de CP reduziu substancialmente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa S-transferase (GST), glutationa redutase (GSR), glutationa (GSH), enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e níveis de peróxido de hidrogênio (H2O2). Os níveis de ureia, creatinina urinária, urobilinogênio, proteínas urinárias, molécula 1 de lesão renal (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina e a depuração da creatinina foram significativamente reduzidas no grupo tratado com PC. Os resultados demonstraram que a CP aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappa-B (NF-B), fator de necrose tumoral- (TNF-), interleucina-1 (IL-1), interleucina-6 (IL-6) níveis e atividade da ciclooxigenase-2 (COX-2) e danos histopatológicos. No entanto, a administração de CAS apresentou um efeito paliativo contra a toxicidade renal gerada por CP e recuperou todos os parâmetros, trazendo-os a um nível normal. Estes resultados revelaram que o CAS é um composto eficaz com potencial curativo para combater o dano renal induzido por CP.

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study

Abstract Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-B), tumor necrosis factor- (TNF-), Interleukin-1 (IL-1), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

Resumo O timerosal é um composto organomercurial, utilizado na preparação de imunoglobulina intramuscular, antivenenos, tintas de tatuagem, antígenos de teste cutâneo, produtos nasais, gotas oftálmicas e vacinas como conservante. Na maioria das espécies animais e nos humanos, o rim é um dos principais locais de deposição de compostos de mercúrio e órgãos-alvo de toxicidade. Assim, a presente pesquisa teve como objetivo avaliar a nefrotoxicidade induzida pelo timerosal em ratos machos. Vinte e quatro ratos albinos machos adultos foram categorizados em quatro grupos. O primeiro grupo era um grupo de controle. Ratos do Grupo II, Grupo III e Grupo IV receberam 0,5µg / kg, 10µg / kg e 50µg / kg de timerosal uma vez ao dia, respectivamente. A administração de timerosal diminuiu significativamente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa redutase (GR), glutationa (GSH) e conteúdo de proteína, enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e peróxido de hidrogênio (H2O2) níveis dependentes da dose. Os níveis de nitrogênio ureico no sangue (BUN), creatinina, urobilinogênio, proteínas urinárias, molécula de lesão renal-1 (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina urinária e a depuração da creatinina foram reduzidas de forma dependente da dose nos grupos tratados com timerosal. Os resultados demonstraram que o timerosal aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappaB (NF-B), fator de necrose tumoral- (TNF-), interleucina-1 (IL-1), níveis de interleucina-6 (IL-6) e atividades da ciclooxigenase-2 (COX-2), DNA e danos histopatológicos dependentes da dose. Portanto, os presentes achados verificaram que o timerosal exerceu nefrotoxicidade em ratos albinos machos.

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study / Efeitos toxicológicos do timerosal no rim de rato: um estudo histológico e bioquímico

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

O timerosal é um composto organomercurial, utilizado na preparação de imunoglobulina intramuscular, antivenenos, tintas de tatuagem, antígenos de teste cutâneo, produtos nasais, gotas oftálmicas e vacinas como conservante. Na maioria das espécies animais e nos humanos, o rim é um dos principais locais de deposição de compostos de mercúrio e órgãos-alvo de toxicidade. Assim, a presente pesquisa teve como objetivo avaliar a nefrotoxicidade induzida pelo timerosal em ratos machos. Vinte e quatro ratos albinos machos adultos foram categorizados em quatro grupos. O primeiro grupo era um grupo de controle. Ratos do Grupo II, Grupo III e Grupo IV receberam 0,5µg / kg, 10µg / kg e 50µg / kg de timerosal uma vez ao dia, respectivamente. A administração de timerosal diminuiu significativamente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa redutase (GR), glutationa (GSH) e conteúdo de proteína, enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e peróxido de hidrogênio (H2O2) níveis dependentes da dose. Os níveis de nitrogênio ureico no sangue (BUN), creatinina, urobilinogênio, proteínas urinárias, molécula de lesão renal-1 (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina urinária e a depuração da creatinina foram reduzidas de forma dependente da dose nos grupos tratados com timerosal. Os resultados demonstraram que o timerosal aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappaB (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), níveis de interleucina-6 (IL-6) e atividades da ciclooxigenase-2 (COX-2), DNA e danos histopatológicos dependentes da dose. Portanto, os presentes achados verificaram que o timerosal exerceu nefrotoxicidade em ratos albinos machos.

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study / Efeitos toxicológicos do timerosal no rim de rato: um estudo histológico e bioquímico

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.(AU)

O timerosal é um composto organomercurial, utilizado na preparação de imunoglobulina intramuscular, antivenenos, tintas de tatuagem, antígenos de teste cutâneo, produtos nasais, gotas oftálmicas e vacinas como conservante. Na maioria das espécies animais e nos humanos, o rim é um dos principais locais de deposição de compostos de mercúrio e órgãos-alvo de toxicidade. Assim, a presente pesquisa teve como objetivo avaliar a nefrotoxicidade induzida pelo timerosal em ratos machos. Vinte e quatro ratos albinos machos adultos foram categorizados em quatro grupos. O primeiro grupo era um grupo de controle. Ratos do Grupo II, Grupo III e Grupo IV receberam 0,5µg / kg, 10µg / kg e 50µg / kg de timerosal uma vez ao dia, respectivamente. A administração de timerosal diminuiu significativamente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa redutase (GR), glutationa (GSH) e conteúdo de proteína, enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e peróxido de hidrogênio (H2O2) níveis dependentes da dose. Os níveis de nitrogênio ureico no sangue (BUN), creatinina, urobilinogênio, proteínas urinárias, molécula de lesão renal-1 (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina urinária e a depuração da creatinina foram reduzidas de forma dependente da dose nos grupos tratados com timerosal. Os resultados demonstraram que o timerosal aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappaB (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), níveis de interleucina-6 (IL-6) e atividades da ciclooxigenase-2 (COX-2), DNA e danos histopatológicos dependentes da dose. Portanto, os presentes achados verificaram que o timerosal exerceu nefrotoxicidade em ratos albinos machos.(AU)

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats / Mitigação da nefrotoxicidade induzida pela cisplatina pela casticina em ratos albinos machos

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

A cisplatina (CP) é uma droga antineoplásica poderosa, comumente usada, com vários efeitos colaterais. Casticin (CAS) é considerado um eliminador de radicais livres e um potente antioxidante. A presente pesquisa foi planejada para avaliar o potencial curativo da CAS em lesão renal induzida por PC em ratos albinos machos. Vinte e quatro ratos albinos machos foram distribuídos em quatro grupos iguais. O Grupo 1 foi considerado grupo controle. Os animais do Grupo 2 foram injetados com 5 mg / kg de PB por via intraperitoneal. O Grupo 3 foi cotratado com CAS (50 mg / kg) por via oral e injeção de CP (5 mg / kg). O Grupo 4 foi tratado com CAS (50 mg / kg) por via oral durante todo o experimento. A administração de CP reduziu substancialmente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa S-transferase (GST), glutationa redutase (GSR), glutationa (GSH), enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e níveis de peróxido de hidrogênio (H2O2). Os níveis de ureia, creatinina urinária, urobilinogênio, proteínas urinárias, molécula 1 de lesão renal (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina e a depuração da creatinina foram significativamente reduzidas no grupo tratado com PC. Os resultados demonstraram que a CP aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappa-B (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), interleucina-6 (IL-6) níveis e atividade da ciclooxigenase-2 (COX-2) e danos histopatológicos. No entanto, a administração de CAS apresentou um efeito paliativo contra a toxicidade renal gerada por CP e recuperou todos os parâmetros, trazendo-os a um nível normal. Estes resultados revelaram que o CAS é um composto eficaz com potencial curativo para combater o dano renal induzido por CP.

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats / Mitigação da nefrotoxicidade induzida pela cisplatina pela casticina em ratos albinos machos

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.(AU)

A cisplatina (CP) é uma droga antineoplásica poderosa, comumente usada, com vários efeitos colaterais. Casticin (CAS) é considerado um eliminador de radicais livres e um potente antioxidante. A presente pesquisa foi planejada para avaliar o potencial curativo da CAS em lesão renal induzida por PC em ratos albinos machos. Vinte e quatro ratos albinos machos foram distribuídos em quatro grupos iguais. O Grupo 1 foi considerado grupo controle. Os animais do Grupo 2 foram injetados com 5 mg / kg de PB por via intraperitoneal. O Grupo 3 foi cotratado com CAS (50 mg / kg) por via oral e injeção de CP (5 mg / kg). O Grupo 4 foi tratado com CAS (50 mg / kg) por via oral durante todo o experimento. A administração de CP reduziu substancialmente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa S-transferase (GST), glutationa redutase (GSR), glutationa (GSH), enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e níveis de peróxido de hidrogênio (H2O2). Os níveis de ureia, creatinina urinária, urobilinogênio, proteínas urinárias, molécula 1 de lesão renal (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina e a depuração da creatinina foram significativamente reduzidas no grupo tratado com PC. Os resultados demonstraram que a CP aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappa-B (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), interleucina-6 (IL-6) níveis e atividade da ciclooxigenase-2 (COX-2) e danos histopatológicos. No entanto, a administração de CAS apresentou um efeito paliativo contra a toxicidade renal gerada por CP e recuperou todos os parâmetros, trazendo-os a um nível normal. Estes resultados revelaram que o CAS é um composto eficaz com potencial curativo para combater o dano renal induzido por CP.(AU)

Celecoxib in the treatment of orofacial pain and discomfort in rats subjected to a dental occlusal interference model

Purpose: To evaluate the effect of a selective cyclooxygenase 2 (COX-2) inhibitor on trigeminal ganglion changes and orofacial discomfort/nociception in rats submitted to an experimental model of dental occlusal interference (DOI). Methods: Female Wistar rats (180-200 g) were divided into five groups: a sham group (without DOI) (n=15); and four experimental groups with DOI treated daily with 0.1 mL/kg saline (DOI+SAL), 8, 16, or 32 mg/kg celecoxib (DOI+cel -8, -16, -32) (n=30/group). The animals were euthanized after one, three, and seven days. The bilateral trigeminal ganglia were analyzed histomorphometrically (neuron cell body area) and immunohistochemically (COX-2, nuclear factor-kappa B [NFkB], and peroxisome proliferator-activated receptor-y [PPARy]). A bilateral nociception assay of the masseter muscle was performed. The number of bites/scratches, weight, and grimace scale scores were determined daily. One-way/two-way analysis of variance (ANOVA)/Bonferroni post hoc tests were used (P < .05, GraphPad Prism 5.0). Results: DOI+SAL showed a reduction in neuron cell body area bilaterally, whereas DOI+cel-32 exhibited a significative increase in neuron cell body area compared with DOI+SAL group (P < 0.05). The ipsilateral (P=0.007 and P=0.039) and contralateral (P < 0.001 and P=0.005) overexpression of COX-2 and NFkB and downregulation of PPARy (P=0.016 and P < 0.001) occurred in DOI+SAL, but DOI+cel-32 reverted this alteration. DOI+SAL showed increase in isplateral (P < 0.001) and contralateral (P < 0.001) nociception, an increased number of bites (P=0.010), scratches (P < 0.001), and grimace scores (P=0.032). In the group of DOI+cel-32, these parameters were reduced. Conclusions: Celecoxib attenuated DOI-induced transitory nociception/orofacial discomfort resulting from trigeminal COX-2 overexpression.

To explore the therapeutic effect of Kangfuxiaomi shuan II on cervicitis in rats

ABSTRACT Purpose: The rat cervicitis model was established with 20% phenol glue to explore the therapeutic effect of Kangfuxiaomi shuan II on rat cervicitis and its mechanism. Methods: After modeling, the rats were treated with Shuangzuotai suppository (37.84 mg/kg), Kangfuxiaoyan shuan (205.6 mg/kg) and Kangfuxiaomi shuan II (40, 80, 160 mg/kg). The histopathological changes and injury degree of cervix in rats were evaluated by vulvar inflammation score and organ index. The therapeutic effect of Kangfuxiaomi shuan II on cervicitis was evaluated by detecting the levels of copper-protein (CP), C-reactive protein (CRP), Rat interleukin 6 (IL-6), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and epidermal growth factor (EGF), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in cervical tissue. Results: Compared with the model group, the vulvar inflammation score and cervical index of rats in other groups decreased significantly (P<0.01). Kangfuxiaomi shuan II could significantly reduce the levels of CP, CRP, and MDA in serum of rats with cervicitis, and significantly increase the activity of SOD in serum of rats with cervicitis (P<0.01). The levels of EGF and iNOS in cervical tissue of rats also increased in different degrees, while the level of COX-2 decreased significantly (P<0.01), which significantly improved the pathological degree of vulvar inflammation in rats with cervicitis. Conclusions: Kangfuxiaomi shuan II has a certain therapeutic effect on cervicitis in rats, and its mechanism may be related to the regulation of inflammatory cytokine network and immunity.

Histomorphological and immunophenotypic characterizationof feline injection site-associated sarcoma

Background: Feline Injection Site-Associated Sarcoma (FISS) is a mesenchymal neoplasia of aggressive behavior thatdevelops in sites where vaccine or drugs were administered. FISS is clinically characterized by the appearance of asolitary firm nodule or a diffuse mass, adhered to tissues, in regions associated to vaccine or drug applications. Despitelow prevalence, tumor recurrence rates can reach 80%. FISS present more aggressive histological characteristics whencompared to sarcomas not associated to injection sites. The aim of this paper is to contribute towards the understandingof the biological behavior of FISS.Materials, Methods & Results: Sixteen samples of FISS were analyzed. Fibrosarcomas were the most frequent histological subtype (62.5%). Malignant peripheral nerve sheath tumor was diagnosed in 18.75% cases. Ten (62.5%) FISS wereclassified as grade II; 4/16 (25%) grade I, and 2/16 (12.5%) grade III. Cox-2 overexpression occurred in 3/16 (18.75%)samples, with positive correlation between Cox-2 expression and cellularity (r = 0.696, P = 0.003). Mitotic index lowerthan 9 events was found in 11/16 (68.7%) samples and between 10 and 19 mitotic events in 5/16 (31.3%) cases. MeanKi-67 expression was 2.39 ± 2.48%. FISS characterized as fibrosarcomas presented longer overall survival (median 545days) than other histological subtypes (median 130.5 days) [P = 0.01].Discussion: Patients with FISS generally present with larger nodules than those with sarcomas not associated to injections,suggesting a challenge for pet owners to note subcutaneous tumors in the interscapular region, in addition to the aggressivebiological behavior of FISS. The influence of size on prognosis remains controversial. An association between histologicgrade and the development of metastasis has been observed, with patients with grade III FISS associated with an increasein the metastatic rate. The present study did not find a correlation between overall survival...

Histomorphological and immunophenotypic characterizationof feline injection site-associated sarcoma

Background: Feline Injection Site-Associated Sarcoma (FISS) is a mesenchymal neoplasia of aggressive behavior thatdevelops in sites where vaccine or drugs were administered. FISS is clinically characterized by the appearance of asolitary firm nodule or a diffuse mass, adhered to tissues, in regions associated to vaccine or drug applications. Despitelow prevalence, tumor recurrence rates can reach 80%. FISS present more aggressive histological characteristics whencompared to sarcomas not associated to injection sites. The aim of this paper is to contribute towards the understandingof the biological behavior of FISS.Materials, Methods & Results: Sixteen samples of FISS were analyzed. Fibrosarcomas were the most frequent histological subtype (62.5%). Malignant peripheral nerve sheath tumor was diagnosed in 18.75% cases. Ten (62.5%) FISS wereclassified as grade II; 4/16 (25%) grade I, and 2/16 (12.5%) grade III. Cox-2 overexpression occurred in 3/16 (18.75%)samples, with positive correlation between Cox-2 expression and cellularity (r = 0.696, P = 0.003). Mitotic index lowerthan 9 events was found in 11/16 (68.7%) samples and between 10 and 19 mitotic events in 5/16 (31.3%) cases. MeanKi-67 expression was 2.39 ± 2.48%. FISS characterized as fibrosarcomas presented longer overall survival (median 545days) than other histological subtypes (median 130.5 days) [P = 0.01].Discussion: Patients with FISS generally present with larger nodules than those with sarcomas not associated to injections,suggesting a challenge for pet owners to note subcutaneous tumors in the interscapular region, in addition to the aggressivebiological behavior of FISS. The influence of size on prognosis remains controversial. An association between histologicgrade and the development of metastasis has been observed, with patients with grade III FISS associated with an increasein the metastatic rate. The present study did not find a correlation between overall survival...(AU)

Comparação entre o efeito do Piroxicam e do Trocoxil, no controle da inflamação em neoplasias mamárias de cadelas utilizando a termografia / Thermographic comparison between piroxicam and trocoxil anti inflammatory effects in canine mammary tumors

Malignant mammary tumors are most prevalent neoplasms in bitches. Currently, it is known the influence of several factors and biological markers involved in tumors development, such as cyclooxygenase-2. Use of non-steroidal anti-inflammatory drugs appears as a promising adjuvant treatment. The aim of this study was to evaluate and to compare the effectiveness of piroxicam and Trocoxil® (mavacoxib) in reduce the peritumoral temperature. At random, it was selected 16 middle-aged bitches presenting mammary tumor according the routine of the Veterinary Hospital. On day 0, after clinical examination and thermography of both mammary chains, piroxicam was prescribed to group 1 (n=12) (0.3mg/kg, VO, SID, 10 days) and to group 2 (n=4) was prescribed Trocoxil® (2mg/kg, VO, single dose). After 10 days, the animals returned for further evaluation and the second thermography. The images were analyzed, tabulated and submitted to statistical analysis by the SigmaPlot® program in a simple t-test, considering p<0.05. The results indicated that Trocoxil® showed a better ability to reduce peritumoral temperature than piroxicam after 10 days of treatment (p=0.041), suggesting this drug with better efficiency in the adjuvant treatment of mammary neoplasms in bitches.

Comparação entre o efeito do Piroxicam e do Trocoxil, no controle da inflamação em neoplasias mamárias de cadelas utilizando a termografia / Thermographic comparison between piroxicam and trocoxil anti inflammatory effects in canine mammary tumors

Malignant mammary tumors are most prevalent neoplasms in bitches. Currently, it is known the influence of several factors and biological markers involved in tumors development, such as cyclooxygenase-2. Use of non-steroidal anti-inflammatory drugs appears as a promising adjuvant treatment. The aim of this study was to evaluate and to compare the effectiveness of piroxicam and Trocoxil® (mavacoxib) in reduce the peritumoral temperature. At random, it was selected 16 middle-aged bitches presenting mammary tumor according the routine of the Veterinary Hospital. On day 0, after clinical examination and thermography of both mammary chains, piroxicam was prescribed to group 1 (n=12) (0.3mg/kg, VO, SID, 10 days) and to group 2 (n=4) was prescribed Trocoxil® (2mg/kg, VO, single dose). After 10 days, the animals returned for further evaluation and the second thermography. The images were analyzed, tabulated and submitted to statistical analysis by the SigmaPlot® program in a simple t-test, considering p<0.05. The results indicated that Trocoxil® showed a better ability to reduce peritumoral temperature than piroxicam after 10 days of treatment (p=0.041), suggesting this drug with better efficiency in the adjuvant treatment of mammary neoplasms in bitches.(AU)

Síndrome da lise tumoral induzida pelo uso do firocoxibe, em cadela acometida com carcinoma mamário inflamatório: relato de caso / Tumoral lysis syndrome induced by the use of firocoxib, in a female dog with inflammatory mammary carcinoma: case report

Síndrome da lise tumoral é considerada uma emergência metabólica grave, caracterizada pela liberação de substâncias citotóxicas na circulação sanguínea, podendo acarretar acidose lática, distúrbio eletrolítico e elevado risco de morte em um período de evolução relativamente pequeno. É considerada uma condição rara em pequenos animais e pouco relatada na literatura veterinária, principalmente quando associada à presença de neoplasmas sólidos. Este relato correlaciona o uso do antiinflamatório não esteróide firocoxibe, utilizado como base terapêutica na remissão da reação inflamatória neoplásica, com o desenvolvimento abrupto da síndrome da lise tumoral, em um paciente canino, da raça Schnauzer miniatura, acometido com carcinoma mamário inflamatório em estágio inicial.(AU)

Tumor Lysis Syndrome is considered a serious metabolic emergency, characterized by the release of cytotoxic substances into the bloodstream, which can lead to lactic acidosis, electrolyte disturbance, and high risk of death in a relatively small clinical course. It is considered a rare condition in small animals, especially when associated with the presence of solid neoplasms. This report correlates the influence of the use of the non-steroidal anti-inflammatory firocoxib, used as a therapeutic base in the remission of the neoplastic inflammatory reaction, and as a consequence there was the abrupt development of the Tumor Lysis Syndrome in a canine patient of the miniature Schnauzer breed, with early inflammatory breast carcinoma.(AU)

Comparative study of four different types of intraperitoneal mesh prostheses in rats

Purpose: To compare four types of mesh regarding visceral adhesions, inflammatory response and incorporation. Methods: Sixty Wistar rats were divided into four groups, with different meshes implanted intraperitoneally: polytetrafluoroethylene (ePTFE group); polypropylene with polydioxanone and oxidized cellulose (PCD); polypropylene (PM) and polypropylene with silicone (PMS). The variables analyzed were: area covered by adhesions, incorporation of the mesh and inflammatory reaction (evaluated histologically and by COX2 immunochemistry). Results: The PMS group had the lowest adhesion area (63.1%) and grade 1 adhesions. The ePTFE and PM groups presented almost the total area of their surface covered by adherences (99.8% and 97.7% respectively).The group ePTFE had the highest percentage of area without incorporation (42%; p <0.001) with no difference between the other meshes. The PMS group had the best incorporation rate. And the histological analysis revealed that the inflammation scores were significantly different. Conclusions: The PM mesh had higher density of adherences, larger area of adherences, adherences to organs and percentage of incorporation. ePTFE had the higher area of adherences and lower incorporation. The PMS mesh performed best in the inflammation score, had a higher incorporation and lower area of adherences, and it was considered the best type of mesh.(AU)

Transcriptomic analysis of differential gene expression reveals an increase in COX2 levels during in vitro canine herpesvirus infection / Análise transcriptômica da expressão gênica diferencial revela um aumento nos níveis de COX2 durante a infecção in vitro por herpesvirus canino

Canine herpesvirus (CaHV-1) affects canids worldwide, causing death in neonates and immunosuppressed hosts. Acute infection by CaHV-1 can cause reproductive, respiratory, and neurological problems in adult animals. Viral pathogenesis and host genes expressions during of CaHV-1infection are not clearly understood. In the present study, the transcriptome of canine kidney cell Mardin-Darby (MDCK) infected in vitro with canine herpesvirus was explored. For this, RNA sequencing (RNA-seq) of the samples in different moments during infection was carried out. Subsequently, the transcriptomic analysis genes related to cell activities and process involved to viral cycle infection were evaluated until 32h post-inoculation (pi). Among evaluated genes, was verified a significant and gradative increase of the prostaglandin-endoperoxide synthase 2 (PTGS2) or cyclooxygenase 2 (COX2) gene expression, throughout of infection, though differential gene expression analysis and validated by quantitative reverse transcription PCR (RT-qPCR). High COX2 expression is usually induced in response to inflammation, pathogens or activation of the immune system but can be a viral mechanism to favor viral replication. Thus, COX2 level increase can be a favorable factor for viral infection with Cahv-1 virus and the use of selective COX2 inhibitors may be beneficial for limiting the infection or clinical signs by causing interruption of the viral replication cycle during active infection. Additionally, the regulation genes expression differential verified in this study can contribute to determining important targets for inhibiting canine herpesvirus infection either by cellular or viral mechanisms.(AU)

O herpesvírus canino (CaHV-1) afeta os canídeos em todo o mundo, causando morte em neonatos e hospedeiros imunossuprimidos. A infecção aguda por CaHV-1 pode causar problemas reprodutivos, respiratórios e neurológicos em animais adultos. A patogênese viral e expressão de genes hospedeiros durante a infecção por CaHV-1 ainda não são bem compreendidos. No presente estudo, o transcriptoma de células de rim canino Madin-Darby (MDCK) infectadas in vitro com herpesvirus canino foi explorado. Para isso, foi realizado o sequenciamento de RNA (RNA-seq) de amostras coletadas em diferentes momentos durante a infecção. Subsequentemente, a análise transcriptômica dos genes relacionados à atividade celular e aos processos envolvidos no ciclo de infecção do vírus foram avaliadas até 32 horas após a inoculação (pi). Dentre os genes avaliados, constatamos uma elevação significativa e gradativa da expressão da Prostaglandina-endoperoxide sintase 2 (PTGS2) ou ciclooxigenase 2 (COX2), ao longo da infecção viral, foi verificada por análise de expressão gênica diferencial e validada por resultados de transcrição reversa por PCR quantitativo (RT-qPCR). O aumento da expressão de COX2 geralmente é induzida em resposta a inflamação, patógenos ou ativação do sistema imune, mas também pode ser um mecanismo para favorecer a replicação viral. Assim, o aumento do nível de COX2 pode ser um fator favorável à infecção viral pelo vírus CaHV-1 e o uso de inibidores seletivos da COX2 pode ser benéfico para limitar a infecção ou os sinais clínicos, causando a interrupção do ciclo de replicação viral durante a infecção ativa. Além disso, a regulação diferencial da expressão dos genes verificados neste estudo podem contribuir para determinar alvos importantes para inibir a infecção por herpesvírus canino, seja por mecanismos celulares ou virais.(AU)

Firocoxib on hematological and biochemical parameters and anesthesia propofol dose in dogs

This study evaluated the hematological and biochemical changes, the safety, as well as the change in propofol dose required for anesthesia induction in dogs, pretreated or not, in response to a single dose or continuous use of the nonsteroidal antiinflammatory drug (NSAID) firocoxib. Thirty animals mean weighing 8.1 kg and mean aged 3.38 years were included. The animals were then divided into groups: Group I (GI) did not receive firocoxib, Group II (GII) received a single dose (5 mg/kg) 90 minutes before anesthesia induction, and Group III (GIII) received the same dose (5 mg/kg) for 40 consecutive days before induction of anesthesia with propofol. Hematological and biochemical evaluations were conducted. The times of collection were defined by the mean time of maximum concentration and constant concentration in the blood of the NSAID. All variables remained within the reference range, but averages differed statistically between GII and GIII, according to the Tukey test (p < 0.05). The average doses of propofol were 6.6 mg/kg, 6.1 mg/kg, and 7.8 mg/kg for GI, GII, and GIII, respectively. Hematological and biochemical changes and increased propofol dose for induction of anesthesia in GIII, despite this can be safely used in association with propofol at the time of anesthesic induction; which must be taken into account because it may also change doses of the drug in other anesthetic methods.(AU)

Firocoxib on hematological and biochemical parameters and anesthesia propofol dose in dogs

This study evaluated the hematological and biochemical changes, the safety, as well as the change in propofol dose required for anesthesia induction in dogs, pretreated or not, in response to a single dose or continuous use of the nonsteroidal antiinflammatory drug (NSAID) firocoxib. Thirty animals mean weighing 8.1 kg and mean aged 3.38 years were included. The animals were then divided into groups: Group I (GI) did not receive firocoxib, Group II (GII) received a single dose (5 mg/kg) 90 minutes before anesthesia induction, and Group III (GIII) received the same dose (5 mg/kg) for 40 consecutive days before induction of anesthesia with propofol. Hematological and biochemical evaluations were conducted. The times of collection were defined by the mean time of maximum concentration and constant concentration in the blood of the NSAID. All variables remained within the reference range, but averages differed statistically between GII and GIII, according to the Tukey test (p < 0.05). The average doses of propofol were 6.6 mg/kg, 6.1 mg/kg, and 7.8 mg/kg for GI, GII, and GIII, respectively. Hematological and biochemical changes and increased propofol dose for induction of anesthesia in GIII, despite this can be safely used in association with propofol at the time of anesthesic induction; which must be taken into account because it may also change doses of the drug in other anesthetic methods.

Cyclooxygenase-2 expression in epithelial neoplasms and its relevance as a targeted therapy in dogs / Expressão de ciclooxigenase-2 em neoplasias epiteliais e sua relevância como terapia alvo em cães

Targeted therapy of neoplasms is an emergent approach in human and veterinary medicine. Cyclooxygenase (COX) is a class of catalytic enzymes related to the formation of inflammatory mediators. COX-2 is expressed constitutively in a few body tissues, but it may be induced in specific pathophysiologic conditions, such as cancer. COX-2 expression in neoplams may be considered a potential predictive factor, due to the possible association of selective COX-2 inhibitors in adjuvant treatments. This scientific communication has the objective to report COX-2 expression in seven neoplasms of dogs and the usage of adjuvant treatment with COX-2 selective inhibitors as an effective and feasible option in cancer treatment.(AU)

O tratamento direcionado das neoplasias é uma abordagem emergente tanto na medicina humana, quanto na veterinária. A cicloxigenase (COX) é uma classe de enzimas catalíticas relacionada à formação de mediadores inflamatórios. A COX-2é expressa de forma constitutiva em poucos tecidos, mas pode ser induzida em condições patofisiológicas específicas, como os processos neoplásicos. A expressão da COX-2 em neoplasias pode ser considerada um fator preditivo em potencial, tendo em vista a possibilidade de associação de inibidores seletivos para COX-2 em tratamentos adjuvantes. Esta comunicação científica teve como objetivo relatar a expressão de COX-2 em neoplasias de sete cães e o tratamento adjuvante com inibidores seletivos para COX-2 como uma opção efetiva e viável no tratamento do câncer.(AU)

Ciclooxygenase inhibitor and metronomic chemotherapy association for the treatment of metastatic anal sac carcinoma in dog: case report / Inibidor de ciclo-oxigenase associado à quimioterapia metronômica no tratamento de carcinoma de saco anal metastático canino: relato de caso

Metronomic chemotherapy consists of an anticancer modality treatment. It is applicable in patients at an advanced stage, with the objective of increasing overall survival. The aim of this study was to report an anal sac apocrine carcinoma case in a dog with lymph node metastasis treated with metronomic chemotherapy sequential to surgery and conventional chemotherapy using gemcitabine and carboplatin. Metronomic chemotherapy was associated with cyclooxygenase-2 (COX-2) inhibitors, due to strong tumor COX-2 immunohistochemistry expression. Metronomic chemotherapy was initiated with cyclophosphamide, but it was replaced by lomustine, also in metronomic dosage, due to adverse effects. Treatment showed effectiveness, since the patient's overall survival exceeded 1095 days (36 months), considerably higher than the mean overall survival expected for this pathology.(AU)

Quimioterapia metronômica consiste em uma modalidade de tratamento anticancerígeno, aplicável a pacientes em estadiamento avançado, com o objetivo de aumentar a sobrevida global. O objetivo deste trabalho foi relatar um caso de carcinoma apócrino do saco anal, em uma cadela, com metástase em linfonodo tratado com quimioterapia metronômica sequencial à cirurgia e quimioterapia convencional utilizando-se gencitabina e carboplatina. O tratamento metronômico foi associado ao uso de inibidores de ciclo-oxigenase-2 (COX-2), baseando-se na constatação de sua expressão tumoral. A terapia metronômica iniciou-se com ciclofosfamida, mas houve necessidade de substituição pela lomustina, também em dose metronômica, devido à ocorrência de efeitos adversos. O tratamento mostrou ser eficaz, pois a sobrevida do paciente ultrapassa 1095 dias (36 meses) desde a cirurgia, sendo consideravelmente maior que a média relatada para essa patologia.(AU)