Redox profile and mediators of the unfolded protein response (UPR) in the placenta of rats during pregnancy.

CONTEXT: Proliferation, differentiation, migration and apoptosis of trophoblastic cells are influenced by hypoxia, as well as adequate modulation of oxidative stress and the unfolded protein response (UPR) pathway. AIMS: We aimed to evaluate the expression profile of redox and UPR mediators in the placenta of rats throughout pregnancy. METHODS: Placental expression of hypoxia-inducible factor 1α (HIF1α), 8-Hydroxy-2'-deoxyguanosine (8-OHdG), superoxide dismutase 1 (SOD1), glutathione peroxidase (GPX), catalase (Cat), activating transcription factor 6 (ATF6), protein kinase RNA-like endoplasmic reticulum kinase (PERK), 78 kD glucose-regulated protein (GRP78) and C/EBP-homologous protein (CHOP), as well as reactive oxygen species (ROS) and peroxynitrite production, were evaluated in Wistar rats on the 10th, 12th, 14th, 16th and 18th day of pregnancy (DP). KEY RESULTS: Increased immunostaining of HIF1α was observed on the 16th and 18th DP, while 8-OHdG and ROS production were greater on the 14th DP. SOD1 and Cat had increased immunostaining on the 14th and 18th DP, while staining of GPX1/2, GRP78 and CHOP was greater on the 18th DP. With regard to gene expression, Hif1α and Sod1 showed increased mRNA expression on the 12th and 16th DP, while Gpx1 had increased expression on the 10th and 16th DP. Cat , Perk and Grp78 gene expression was greater on the 14th DP, unlike Atf6 , which showed greater expression on the 12th DP. In contrast, Chop maintained increased expression from the 12th to the 18th DP. CONCLUSIONS: The placental expression of redox and UPR mediators in rats is influenced by gestational age, with greater expression in periods of greater HIF1α and 8-OHdG expression and at the end of the pregnancy. IMPLICATIONS: This study provides data on the physiological modulation of redox and UPR mediators during placental development in rats.

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.

Analgesic effects of Phα1ß toxin: a review of mechanisms of action involving pain pathways

Phα1ß is a neurotoxin purified from spider venom that acts as a high-voltage-activated (HVA) calcium channel blocker. This spider peptide has shown a high selectivity for N-type HVA calcium channels (NVACC) and an analgesic effect in several animal models of pain. Its activity was associated with a reduction in calcium transients, glutamate release, and reactive oxygen species production from the spinal cord tissue and dorsal ganglia root (DRG) in rats and mice. It has been reported that intrathecal (i.t.) administration of Phα1ß to treat chronic pain reverted opioid tolerance with a safer profile than ω-conotoxin MVIIA, a highly selective NVACC blocker. Following a recent development of recombinant Phα1ß (CTK 01512-2), a new molecular target, TRPA1, the structural arrangement of disulphide bridges, and an effect on glial plasticity have been identified. CTK 01512-2 reproduced the antinociceptive effects of the native toxin not only after the intrathecal but also after the intravenous administration. Herein, we review the Phα1ß antinociceptive activity in the most relevant pain models and its mechanisms of action, highlighting the impact of CTK 01512-2 synthesis and its potential for multimodal analgesia.

Analgesic effects of Phalfa1 beta toxin: a review of mechanisms of action involving pain pathways

Phα1ß is a neurotoxin purified from spider venom that acts as a high-voltage-activated (HVA) calcium channel blocker. This spider peptide has shown a high selectivity for N-type HVA calcium channels (NVACC) and an analgesic effect in several animal models of pain. Its activity was associated with a reduction in calcium transients, glutamate release, and reactive oxygen species production from the spinal cord tissue and dorsal ganglia root (DRG) in rats and mice. It has been reported that intrathecal (i.t.) administration of Phα1ß to treat chronic pain reverted opioid tolerance with a safer profile than ω-conotoxin MVIIA, a highly selective NVACC blocker. Following a recent development of recombinant Phα1ß (CTK 01512-2), a new molecular target, TRPA1, the structural arrangement of disulphide bridges, and an effect on glial plasticity have been identified. CTK 01512-2 reproduced the antinociceptive effects of the native toxin not only after the intrathecal but also after the intravenous administration. Herein, we review the Phα1ß antinociceptive activity in the most relevant pain models and its mechanisms of action, highlighting the impact of CTK 01512-2 synthesis and its potential for multimodal analgesia.

Analgesic effects of Ph1 toxin: a review of mechanisms of action involving pain pathways

Abstract Ph1 is a neurotoxin purified from spider venom that acts as a high-voltage-activated (HVA) calcium channel blocker. This spider peptide has shown a high selectivity for N-type HVA calcium channels (NVACC) and an analgesic effect in several animal models of pain. Its activity was associated with a reduction in calcium transients, glutamate release, and reactive oxygen species production from the spinal cord tissue and dorsal ganglia root (DRG) in rats and mice. It has been reported that intrathecal (i.t.) administration of Ph1 to treat chronic pain reverted opioid tolerance with a safer profile than -conotoxin MVIIA, a highly selective NVACC blocker. Following a recent development of recombinant Ph1 (CTK 01512-2), a new molecular target, TRPA1, the structural arrangement of disulphide bridges, and an effect on glial plasticity have been identified. CTK 01512-2 reproduced the antinociceptive effects of the native toxin not only after the intrathecal but also after the intravenous administration. Herein, we review the Ph1 antinociceptive activity in the most relevant pain models and its mechanisms of action, highlighting the impact of CTK 01512-2 synthesis and its potential for multimodal analgesia.

Efeitos fetais e maternos do propofol, etomidato, tiopental e anestesia epidural, em cesariana eletivas de cadelas / Fetal and maternal effects of propofol, etomidate, tiopental and epidural anesthesia, in bitches elective caesarian section

O objetivo deste trabalho foi comparar os efeitos entre os fármacos indutores de anestesia como propofol, etomidato e tiopental, e a anestesia epidural com lidocaína seguida de indução, em cadelas submetidas à cesariana, e seus neonatos. Para tanto, foram utilizadas 20 cadelas e 129 filhotes distribuídos em quatro grupos. No grupo 1 (5 cadelas e 39 neonatos), a indução anestésica foi feita com propofol; no grupo 2 (5 cadelas e 25 neonatos), com etomidato; no grupo 3 (5 cadelas e 26 neonatos) com tiopental e no grupo 4, (5 cadelas e 39 neonatos) utilizou-se anestesia epidural e indução com halotano através de máscara. Em todos os casos, a medicação pré-anestésica foi feita com midazolam na dose de 0,22mg kg-1 via IM, e a manutenção anestésica com halotano em circuito semifechado e concentração inicial de 3V por cento. As variáveis avaliadas nas cadelas foram: temperatura retal, freqüência cardíaca, freqüência respiratória, saturação da oxi-hemoglobina (SpO2), pressão arterial média. Para a avaliação dos recém-nascidos, foram mensurados: freqüência cardíaca, esforço respiratório, movimentos musculares, coloração das mucosas e irritabilidade reflexa interpretados através do escore de Apgar modificado, bem como a SpO2 do neonato. Os resultados mostraram que todos os protocolos foram adequados para as mães com mínimos efeitos sistêmicos. Para o neonato, a utilização de anestesia epidural na mãe, seguida de indução e manutenção com halotano foi superior aos protocolos que usaram agentes injetáveis na indução anestésica.

Butorfanol na anestesia com propofol em gatas pré-tratadas com levomepromazina / Butorphanol on the anesthesia by propofol in female cats premedicated with levomepromazine

Objetivando avaliar a influência do butorfanol na anestesia com propofol na espécie felina, durante ovariosalpingohisterectomia eletiva, utilizaram-se 20 gatas, adultas, distribuídas em dois grupos (G1 e G2) de igual número. O G1 foi pré-tratado com levomepromazina (1mg/kg via IM), enquanto no G2 adicionou-se butorfanol na dose de 0,4mg/kg via IM, à pré-medicaçäo. A induçäo anestésica foi feita com propofol IV, em dose suficiente para permitir a intubaçäo. Para a manutençäo da anestesia por 60 minutos, o propofol foi utilizado em doses complementares de 3 mg/kg, sempre que necessário. Em ambos os grupos, houve reduçäo significativa da temperatura corporal, com valores abaixo do considerado fisiológico para a espécie. Os demais parâmetros fisiológicos (freqüências cardíaca e respiratória e pressäo arterial), de uma forma geral, tiveram alteraçöes porém sem significado clínico para a espécie. As concentraçöes de cortisol sérico no G2 permaneceram dentro dos limites considerados fisiológicos, enquanto no G1 houve elevaçäo desses valores durante o procedimento cirúrgico. Assim, pode-se concluir que o butorfanol näo reduziu a dose do propofol, porém determinou maior conforto para os animais durante a cirurgia o que indicaria a sua inclusäo em protocolos anestésicos para esta espécie