Evaluation of the Therapeutic Potential of Amantadine in a Vincristine-Induced Peripheral Neuropathy Model in Rats.

This study aimed to evaluate the therapeutic potential of amantadine in a vincristine-induced peripheral neuropathy model in rats. Forty-eight male Wistar rats were used. The treated groups received oral amantadine at doses of 2, 5, 12, 25 and 50 mg/kg, with daily applications for 14 days. The mechanical paw withdrawal threshold was measured using a digital analgesimeter. Immunohistochemical analysis of IL-6, TNFα, MIP1α, IL-10, CX3CR1, CXCR4, SOD, CAT and GPx, and enzymatic activity analysis of CAT, SOD and GPx were performed, in addition to quantitative PCR of Grp78, Chop, Ho1, Perk, Bax, Bcl-xL, Casp 3, Casp 9, IL-6, IL-10, IL-18 and IL-1ß. The results showed an increase in nociceptive thresholds in animals that received 25 mg/kg and 50 mg/kg amantadine. Immunohistochemistry showed a decrease in the immunostaining of IL-6, TNFα, MIP1α and CX3CR1, and an increase in IL-10. CAT and SOD showed an increase in both immunochemistry and enzymatic analysis. qPCR revealed a reduced expression of genes related to endoplasmic reticulum stress and regulation in the expression of immunological and apoptotic markers. Amantadine demonstrated antinociceptive, anti-inflammatory and antioxidant effects in the vincristine-induced peripheral neuropathy model in rats, suggesting that amantadine may be considered an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

Post-treatment with maropitant reduces oxidative stress, endoplasmic reticulum stress and neuroinflammation on peripheral nerve injury in rats.

OBJECTIVE: To determine the effective dose and therapeutic potential of maropitant using through expression of mediators of oxidative stress, inflammatory and of the unfolded protein response (UPR) (bio) markers on spinal cord using a model of neuropathic pain induced through chronic constriction injury (CCI) in rats. STUDY DESIGN: Randomized, blinded, prospective experimental study. ANIMALS: 98 male Wistar rats. METHODS: Rats were anesthetized with sevoflurane and after CCI, they were randomly assigned to the following groups that received: vehicle, 3, 6, 15, 30 e 50 mg/kg/24q of maropitant. The effect on inflammatory mediators (IL10, TNFα), oxidative stress (GPx, CAT, SOD), microglial (IBA-1) and neuronal (NeuN, TACR1) markers was evaluated though immunohistochemistry and expression levels of markers of hypoxia (HIF1α, Nrf2), antioxidant enzymes (Catalse, Sod1 and GPx1), and endoplasmic reticulum stress mediators (GRP78, CHOP and PERK) through qRT-PCR. RESULTS: Intraperitoneal injection (IP) of maropitant inhibited nociception with ID50 values of 4,1 mg/kg (5,85-19,36) in a neuropathic pain model through CCI. A dose of 30 mg/kg/24q was significantly effective in reducing mechanical allodynia 1 to 4h after treatment with nociception inhibition (145,83%). A reduction in the expression of hypoxia factors (HIF1α, Nrf2) was observed, along with an increase in antioxidant activity (CAT, SOD and GPX). Additionally, there was a reduction in inflammatory markes (IL10, TNFα), microglial (IBA-1), and neuronal markers (NeuN, TACR1). CONCLUSION AND CLINICAL RELEVANCE: These findings demonstrate that the determined dose, administered daily for seven days, had an antinociceptive effect, as well as anti-inflammatory and antioxidant activity.

Efficacy of Preemptive Analgesia with Amantadine for Controlling Postoperative Pain in Cats Undergoing Ovariohysterectomy.

This study aimed to evaluate the effect of the preemptive administration of amantadine on postoperative analgesia in cats undergoing ovariohysterectomy and its influence on the physiological parameters. Twenty healthy domestic cats scheduled to undergo ovariohysterectomy at the Santa Cruz State University, Ilhéus, were divided into two groups: the control group (Group C; n = 10) and the amantadine group (Group A; n = 10). The cats in Group C received placebo capsules 30 min prior to the standard anesthetic protocol, whereas those in Group A received 5 mg/kg of amantadine orally 30 min prior to the standard anesthetic protocol. Postoperative pain was assessed using the visual analog scale and the UNESP-Botucatu multidimensional scale for the evaluation of postoperative pain in cats. The administration of amantadine had no effect on the physiological parameters evaluated. The pain scores in Group A were lower than those in Group C, indicating that the frequency of rescue analgesic administration cats in Group A was lower. That way, preemptive oral administration of amantadine at a dose of 5 mg/kg was effective at controlling postoperative pain in cats undergoing ovariohysterectomy. Moreover, no adverse effects or alterations in the physiological patterns were observed in the treated animals.

Expression profile of the Kisspeptin/Kiss1r system and angiogenic and immunological mediators in the ovary of cyclic and pregnant cats.

The Kisspeptin/Kiss1r system has been studied in mammalian ovaries. However, there are still no studies on the modulation of this system and its relationship with angiogenic and immunological mediators in the ovary of domestic cats, especially during pregnancy. We evaluated the expression of Kisspeptin/Kiss1r and angiogenic and immunological mediators during folliculogenesis, luteogenesis and luteal regression of cyclic and pregnant cats. The ovary exhibited moderate to intense expression for Kiss1, VEGF, Flk-1, INFγ and MIF in oocytes and the follicular wall, while Kiss1r expression was low in granulosa cells. In these cells, there was also a greater expression of Kiss1, INFγ and MIF, mainly in secondary follicles, while tertiary and preovulatory follicles exhibited greater expression of VEGF and Flk-1 in this layer. In luteogenesis, Kiss1 immunostaining was higher in mature corpora lutea (MCL) of pregnant cats compared to vacuolated CL (VCL) and corpus albicans (CA). Pregnancy also increased the luteal gene expression of Kiss1 as well as Kiss1, Kiss1r, Flk-1, and MIF immunostaining in MCL, while reduced the area of VEGF expression in VCL and luteal mRNA expression of Mif when compared to non-pregnant animals. In addition, positive gene correlation between Kiss1r and Mif was observed in the CL. Kiss1, Kiss1r, Vegf and Mif expression were lower in the CA of cats in anestrus. These findings reveal that the expression of Kisspeptin/Kiss1r and angiogenic and immunological mediators, in the ovary of domestic cats, depend on the follicular and luteal stage, and the luteal expression of these mediators is influenced by pregnancy.

Antinociceptive and analgesic effect of continuous intravenous infusion of maropitant, lidocaine and ketamine alone or in combination in cats undergoing ovariohysterectomy.

BACKGROUND: Multimodal analgesia consists of the combination of analgesic drugs at low doses to act in different places along the path of pain. Studies with continuous infusion of analgesic drugs in cats are not common. This study aimed to evaluate the analgesic effect of maropitant, lidocaine and ketamine alone or in combination (intravenous bolus + subsequent continuous intravenous infusion) in the management of acute postoperative pain in cats undergoing ovariohysterectomy. Seventy healthy cats undergoing an ovariohysterectomy received a standard anesthetic protocol consisting of acepromazine and morphine, propofol (anesthesia induction), and isoflurane (anesthesia maintenance). The animals were stratified into seven groups (n = 10 in each group): control (CG), maropitant (MG), lidocaine (LG), ketamine (KG), maropitant + lidocaine (LMG), maropitant + ketamine (KMG), and maropitant + lidocaine + ketamine (LKMG). All drugs were injected first as an intravenous bolus and then by continuous intravenous infusion. During surgery, esophageal temperature, respiratory rate, heart rate, oxygen saturation, expired isoflurane concentration, and partial pressure of carbon dioxide at the end of expiration were evaluated at 7 time points. Postoperative pain was evaluated for 6 h after extubation using the visual analogue scale and the UNESP-Botucatu multidimensional composite pain scale for assessing postoperative pain in cats. RESULTS: Adverse effects related to maropitant, lidocaine and ketamine infusion were not observed. Pain scores were lower in the MG, KG and LG groups when compared to the CG group using both scales. Although pain scores were also lower in all combination groups than CG, more animals in these groups required rescue analgesia compared to MG. This indicates that the postoperative analgesic effect of all drugs, either alone or in combination, confers analgesia, although the combinations did not promote greater analgesia. CONCLUSIONS: Continuous intravenous infusion of maropitant, lidocaine, and ketamine alone induces postoperative analgesic effect in cats undergoing ovariohysterectomy, but combinations of these drugs did not increase the analgesic effect. No adverse effect was observed with any drug or their combination.

Tratamento de ferida cirúrgica cutânea em ratos com óleo-resina de copaíba (copaíba reticulata) / Treatment of surgical wounds in rats with copaiba oil-resin (copaiba reticulata)

Foi avaliada a atividade cicatrizante do óleo-resina de copaíba "in natura" em feridas cirúrgicas cutâneas induzidas em ratos. Setenta e dois ratos foram distribuídos em três grupos: Grupo Controle Negativo (GCN), Grupo Controle Positivo (GCP) e Grupo Óleo-resina de Copaíba (GOC). A avaliação da hiperemia por escore na macroscopia mostrou que a chance de um animal apresentar um grau de hiperemia baixo quando tratado com o óleo-resina de copaíba é 1,46 vezes maior que um animal tratado com ácidos graxos essenciais e 2,14 vezes maiores que a chance de um animal tratado com óleo mineral. Com relação ao infiltrado inflamatório na microscopia a probabilidade de ser menor ocorre no GOC em comparação com os GCN e GCP. Em relação ao tempo de reepitelização, a chance de um animal apresentar uma reepitelização mais lenta tratado com ácidos graxos essenciais é de 1,2 vezes a chance de um animal tratado com óleo-resina de copaíba. A análise histológica mostrou que o tecido cicatricial após o tratamento com óleo-resina de copaíba apresentou maior contração da ferida e consequentemente redução do tamanho da ferida visto pela aproximação de anexos da pele no corte histológico. Concluiu-se que o tratamento com óleo-resina de copaíba proporciona maior contração da ferida e aproximação dos anexos da pele.

The healing activity of "in natura" oil-resin of copaíba resin was evaluated in cutaneous surgical wounds induced in rats. Seventy-two rats were divided into three groups: Negative Control Group (GCN), Positive Control Group (GCP) and Copaíba Oil-Resin Group (GOC). Evaluation of hyperemia by macroscopic score showed that the chance of an animal presenting a low degree of hyperemia when treated with copaiba oil-resin is 1.46 times higher than an animal treated with essential fatty acids and 2.14 times greater than the chance of an animal treated with mineral oil. With regard to inflammatory infiltrate under microscopy the probability of being smaller occurs in GOC compared to GCN and GCP. Regarding the time of re-epithelialization, the chance of an animal having a slower reepithelization treated with essential fatty acids is 1.2 times the chance of an animal treated with copaiba oil-resin. Histological analysis showed that cicatricial tissue after treatment with copaiba oil-resin presented greater contraction of the wound due to the approximation of skin attachments. It was concluded that the treatment with copaiba oil-resin provides greater contraction of the wound and approximation of the skin attachments.

Kisspeptin/Kiss1r system and angiogenic and immunological mediators at the maternal-fetal interface of domestic cats.

The Kisspeptin/Kiss1r system is a key regulator of reproduction by stimulating gonadotrophin-releasing hormone and luteinizing hormone release, and in vitro studies have shown that Kisspeptin can modulate angiogenesis and immune function, factors that are also essential for reproduction However, there are no studies on the expression of Kisspeptin/Kiss1r at the maternal-fetal interface in domestic cats and its relationship with angiogenic and immunological mediators. Thus, our objective was to evaluate the spatiotemporal expression profile of Kisspeptin/Kiss1r and angiogenic and immunological mediators in the uterus and placenta of domestic cats during pregnancy. Uterus and placenta samples were collected from cats in mid pregnancy (N = 6) and late pregnancy (N = 6), in addition to uterus from non-pregnant cats in diestrus (N = 7), to evaluate protein and gene expression of kisspeptin (Kiss1), kisspeptin receptor (Kiss1r), vascular endothelial growth factor (VEGF), tyrosine kinase receptor (Flk-1), placental growth factor (PLGF), interferon gamma (INFγ), migration inhibiting factor (MIF), tumor necrosis factor (TNFα), interleukins (IL6 and IL10) by immunohistochemistry and quantitative polymerase chain reaction. Pregnancy increased the uterine expression of Kiss1 and Kiss1r, especially at the late pregnancy, in addition to upregulating INFy, MIF, Vegf, Il10, and Tnf and downregulating Plgf. Higher placental expression of Kiss1r and Plgf mRNA occurred at the late pregnancy, while the expression of Kiss1, VEGF, Flk-1, INFy, TNFα, Il6, and IL10 was higher in the mid of pregnancy. A positive correlation between Kiss1 and Tnf was observed in the placenta, while Kiss1r had a negative correlation with Infγ, Il6, and Il10. The findings reveal that Kisspeptin/Kiss1r and angiogenic and immunological mediators at the maternal-fetal interface of pregnant cat have a gene correlation and are modulated by the gestational age. These data suggest possible functional links of Kisspeptin in placental angiogenesis and immunology.

Pyometra and estrous cycle modulate the uterine expression of the kisspeptin system and angiogenic and immune factors in cats.

Failures in hypothalamic kisspeptin/Kiss1r signaling are associated with infertility, and in vitro studies have shown that kisspeptin can modulate angiogenesis and immune activity. Because there is no in vivo research on the functional relationship between these factors in the reproductive system, especially in domestic cats, we evaluated the expression profile of kisspeptin/Kiss1r and angiogenic and immunological mediators in the genital tract of cyclic cats and of those with pyometra. The uterus of cats in diestrus exhibited greater gene and protein expression of Kiss1, as well as Vegf, Pigf, Mif, and Il6. In contrast, Kiss1r presented greater expression in proestrus/estrus, similarly to that observed for the immunostaining of INFγ, MIF, TNFα, and IL10. These factors were positively correlated with Kiss1 and/or Kiss1r, and a positive correlation between Kiss1 and Kiss1r was also observed in the uterus of cats during the estrous cycle. Cats with pyometra showed greater immunostaining of Kiss1 and Kiss1r on the endometrial surface and reduced immunostaining of Kiss1 in deep glands, whereas there was a significant reduction in Vegf, Pigf, Mif, and Il6 mRNA, and an increase in Tnf mRNA. The findings reveal that there is a gene correlation between kisspeptin/Kiss1r and angiogenic and immune mediators in the uterus of the domestic cat, which is modulated by the estrous cycle, and that pyometra affects the expression of these mediators. This study suggests, for the first time, a functional relationship between the Kiss/Kiss1r system and angiogenic and immune mediators in the female genital tract.

Correção De Estenose Uretral Após Uretrostomia Em Gato Relato De Caso / Stenosis Urethral Correction After Urethrostomy Surgery In A Cat Case Report / Corréccion De Estenose Uretral Después De Uretrostomia En Gato Relato De Caso

A doença do trato urinário inferior dos felinos, DTUIF, acomete gatos e tem como sinais clínicos disúria, hematúria e polaciúria. Tais sinais podem estar relacionados a obstrução uretral parcial ou total. Machos tem maior predisposição do que as fêmeas por possuírem a uretra peniana mais estreita, a idade de maior ocorrência é entre dois e seis anos, e ainda animais castrados são mais susceptíveis a desenvolver a doença. Nestes casos a indicação é a desobstrução por meio de cateterização da uretra peniana sob anestesia geral. Em casos recorrentes deve-se indicar a cirurgia de uretrostomia. Este procedimento cirúrgico tem o objetivo de criar uma fístula ligando diretamente a uretra e a pele. O resultado pós-cirúrgico é excelente evitando novas obstruções, mas também é passível de complicações como estenose que ocorre devido ao processo de retração cicatricial, mas pode ser excessiva por falta de cuidados pós-operatórios Este relato tem o objetivo de descrever um caso de estenose após a uretrostomia em um gato que apresentou complicações pós-operatórias e a nova cirurgia para refazer a fístula.(AU)

Feline disease of inferior urinary tract affects cats and its clinical signs are dysuria, hematuria and pollakiuria. This signs are related a parcial or total urethral obstruction. Males have more predisposition than females because their penile urethra are thin. Cats between two and six years old and castrated animals are more susceptible to developing the disease. In this cases is indicated the opening with aid of a probe under general anesthesia. In obstruction recurring cases it should be point a perineal urethrostomy surgery. This objective surgery is create a fistula between the urethra and the skin. The post-operative result are excellent and avoid new obstructions, but can have complications such as stenosis. The stenosis is a normal fact in a healing process, but can be excessive when the lack of care in the post-operative period that allow the animal stir in the wound before the complete healing. This case report presents a urethral stenosis after the urethrostomy surgery in a cat and your treatment.(AU)

La enfermedad del trato urinário inferior de los felinos acomete gatos y tiene como señales clínicos disúria, hematuria y polaciúria. Tales señales pueden estar relaciuonados a La obstrução uretral parcial o total. Machos tienen mayor predisposição que las hembras por tener la uretra peniana mas estrecha, la edad de mayor ocurrencia es entre dos y seis años, y aún animales castrados son más susceptibles a desarrollar la enfermedad. En estos casos la indicación es la desobstrución por médio de cateterizacion de la uretra peniana bajo anestesia general. En casos recurrentes se debe indicar la cirugía de uretrostomia. Este procedimento tiene el objetivo de crear una fístula conectando directamente la uretra y la piel. El resultado post cirúrgico es excelente evitando nuevas obstruciones, pero también es pasible de complicaciones como estenosis que ocurre debido al proceso de retracion cicatricial, pero puede se excesiva por falta de cuidados post operatórios. Este relato tiene el objetivo de describir un caso de estenosis después de la uretrostomia en un gato que presentó complicaciones post operatórias y la nueva cirugía para rehacer la fístula.(AU)

Correção De Estenose Uretral Após Uretrostomia Em Gato Relato De Caso / Stenosis Urethral Correction After Urethrostomy Surgery In A Cat – Case Report / Corréccion De Estenose Uretral Después De Uretrostomia En Gato – Relato De Caso

A doença do trato urinário inferior dos felinos, DTUIF, acomete gatos e tem como sinais clínicos disúria, hematúria e polaciúria. Tais sinais podem estar relacionados a obstrução uretral parcial ou total. Machos tem maior predisposição do que as fêmeas por possuírem a uretra peniana mais estreita, a idade de maior ocorrência é entre dois e seis anos, e ainda animais castrados são mais susceptíveis a desenvolver a doença. Nestes casos a indicação é a desobstrução por meio de cateterização da uretra peniana sob anestesia geral. Em casos recorrentes deve-se indicar a cirurgia de uretrostomia. Este procedimento cirúrgico tem o objetivo de criar uma fístula ligando diretamente a uretra e a pele. O resultado pós-cirúrgico é excelente evitando novas obstruções, mas também é passível de complicações como estenose que ocorre devido ao processo de retração cicatricial, mas pode ser excessiva por falta de cuidados pós-operatórios Este relato tem o objetivo de descrever um caso de estenose após a uretrostomia em um gato que apresentou complicações pós-operatórias e a nova cirurgia para refazer a fístula.

Feline disease of inferior urinary tract affects cats and its clinical signs are dysuria, hematuria and pollakiuria. This signs are related a parcial or total urethral obstruction. Males have more predisposition than females because their penile urethra are thin. Cats between two and six years old and castrated animals are more susceptible to developing the disease. In this cases is indicated the opening with aid of a probe under general anesthesia. In obstruction recurring cases it should be point a perineal urethrostomy surgery. This objective surgery is create a fistula between the urethra and the skin. The post-operative result are excellent and avoid new obstructions, but can have complications such as stenosis. The stenosis is a normal fact in a healing process, but can be excessive when the lack of care in the post-operative period that allow the animal stir in the wound before the complete healing. This case report presents a urethral stenosis after the urethrostomy surgery in a cat and your treatment.

La enfermedad del trato urinário inferior de los felinos acomete gatos y tiene como señales clínicos disúria, hematuria y polaciúria. Tales señales pueden estar relaciuonados a La obstrução uretral parcial o total. Machos tienen mayor predisposição que las hembras por tener la uretra peniana mas estrecha, la edad de mayor ocurrencia es entre dos y seis años, y aún animales castrados son más susceptibles a desarrollar la enfermedad. En estos casos la indicación es la desobstrución por médio de cateterizacion de la uretra peniana bajo anestesia general. En casos recurrentes se debe indicar la cirugía de uretrostomia. Este procedimento tiene el objetivo de crear una fístula conectando directamente la uretra y la piel. El resultado post cirúrgico es excelente evitando nuevas obstruciones, pero también es pasible de complicaciones como estenosis que ocurre debido al proceso de retracion cicatricial, pero puede se excesiva por falta de cuidados post operatórios. Este relato tiene el objetivo de describir un caso de estenosis después de la uretrostomia en un gato que presentó complicaciones post operatórias y la nueva cirugía para rehacer la fístula.

Investigação molecular de Leptospira spp em rins de bovinos / Molecular Research of Leptospira spp in Kidneys of Cattle

Background: Leptospirosis is a zoonotic bacterial disease caused by Leptospira spp. that affects wild and domestic animals and humans. It has a worldwide distribution and causes public health problems and economic losses in livestock. The genus Leptospira is divided basically into two species: the Leptospira interrogans that is pathogenic and Leptospira biflexa that is considered saprobic. Cattle are an important source of infection, mainly to humans who work with these animals such as breeders, cowboys, slaughtermen, veterinarians and agricultural technicians. The temperature and rainfall indices of tropical and subtropical climate regions encourage the continuing disease outbreaks. In humans the symptoms are headache, fever, myalgia, nausea and vomiting. The identification of the disease is possible with some tests such as ELISA, immunofluorescence, bacterial culture, and Polymerase Chain Reaction (PCR). The aim of this work was to perform the molecular research for the presence of Leptospira spp. in kidneys of cattle refuted at a slaughterhouse. Materials, Methods & Results: Two hundred fragments of cattle kidney were collected at slaughterhouse located at Ilhéus, Bahia, Brazil. The macroscopic kidney refutation causes were nefritis, presence of cysts, congestion and presence of whitening and hemorrhagic areas. The kidney samples were placed in plastic containers identified and packed in an isothermal box until arrival at the laboratory, where they were kept at -20°C until the DNA extraction with phenol/chloroform/ isoamyl alcohol (25:24:1). The DNA was quantified by spectrophotometer at 260 nm wavelength. The integrity of DNA was evaluated with 1% agarose gel stained with ethidium bromide and visualized at an ultraviolet light transilluminator. DNA amplification was performed with primers G1- [forward] 5'-CTGAATCGCTGTATAAAAGT-3' and G2- [reverse] 5'-GGAAAACAAATGGTCGGAAG-3' for pathogenic and non-pathogenic Leptospira. Aliquots of 50 ng/µL of extracted DNA were used for PCR reaction. Out of 200 tissue samples, 16 (8%) were positive and the amplified fragments had molecular weight compatible with Leptospira spp. Discussion: The amplicons presented molecular weight compatible with pathogenic and non-pathogenic strains of Leptospira spp. wich may represent a health risk for the ones who may contact animals or consume uncoocked products. Leptospira molecular diagnose may allow the pathogen identification in asymptomatic animals from small DNA amounts. Primers G1 and G2 amplified bacterial 16S rRNA gene area, allowing the identification. The renal tissue alterations identified during inspection, may be associated with Leptospira spp. presence showing the fundamental importance of correct identification and discard of affected organs in order to reduce the bacterial transmission risk. Many articles have being showing the Leptospira cattle prevalence and human risks by contacting these animals. The results presented in this article emphasizes the importance of the cattle as possible transmitters of the pathogen for slaughterhouses workers and meat inspectors, veterinarians as well as rural workers and their families, being critical to conduct orientation and conscientization programs about the problem and ways to combat and control it.