Kahweol, a natural diterpene from coffee, induces peripheral antinociception by endocannabinoid system activation.

Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80 µg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 µg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 µg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 µg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 µg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 µg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 µg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.

Kahweol, a natural diterpene from coffee, induces peripheral antinociception by endocannabinoid system activation

Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80 µg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 μg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 μg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 μg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 μg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 μg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 μg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.

A new surgical technique to treat corneal perforations using amniotic membrane and surgical adhesive / Nova técnica cirúrgica para tratamento de perfuração de córnea utilizando membrana amniótica e adesivo cirúrgico

The objectives of this study were to compare surgical techniques and the effects of using n-butyl 2-cyanoacrylate and bovine amniotic membrane to repair perforated lesions in corneas. Penetrating keratoplasty was performed in sixty New Zealand White rabbits under general anesthesia. Group 1 (G1) was treated with n-butyl 2-cyanoacrylate, group 2 (G2) received a fragment of amniotic membrane through the anterior chamber and application of n-butyl 2-cyanoacrylate over the lesion, group 3 (G3) was treated with the same technique as G2 with the addition of an amniotic membrane bandage covering the cornea and sutured in the limbus region, and group 4 (G4) was treated with an amniotic membrane sutured to the lesion and an amniotic membrane bandage sutured in the limbus region. Clinical, histological and histomorphometric examinations of the corneas were performed. The membrane acted as a barrier for aqueous humor in G2 and G3, thereby keeping the surface dry for adhesive application; it also prevented the adhesive from contacting intraocular structures. The groups treated with amniotic membrane and surgical adhesive showed better results than the groups treated with either material alone. Thus, the combination of the membrane with the adhesive is recommended for this type of lesion.(AU)

Os objetivos deste estudo foram comparar técnicas cirúrgicas e efeitos do n-butil 2-cianoacrilato e da membrana amniótica bovina na reparação de lesões perfuradas em córneas. Sessenta coelhos da raça Nova Zelândia Branca foram submetidos à ceratoplastia penetrante sob anestesia geral. O grupo 1 (G1) foi tratado com n-butil 2-cianoacrilato; o grupo 2 (G2) recebeu um fragmento de membrana amniótica pela câmara anterior e aplicação de n-butil 2-cianoacrilato sobre a lesão; o grupo 3 (G3) foi tratado com a mesma técnica aplicada ao G2, adicionando-se uma bandagem de membrana amniótica cobrindo a córnea e suturada à região do limbo; e o grupo 4 (G4) foi tratado com membrana amniótica suturada nas bordas da lesão e bandagem de membrana amniótica suturada na região do limbo. Foram realizados exames clínico, histológico e histomorfométrico. A membrana atuou como barreira contra o extravasamento do humor aquoso nos grupos 2 e 3, manteve a superfície seca para posterior aplicação do adesivo e impediu o contato do adesivo com as estruturas intraoculares. Os grupos tratados com o adesivo associado à membrana amniótica demonstraram melhores resultados do que aqueles tratados com cada material isoladamente. Assim, a combinação da membrana com o adesivo é indicada neste tipo de lesão.(AU)

A new surgical technique to treat corneal perforations using amniotic membrane and surgical adhesive / Nova técnica cirúrgica para tratamento de perfuração de córnea utilizando membrana amniótica e adesivo cirúrgico

The objectives of this study were to compare surgical techniques and the effects of using n-butyl 2-cyanoacrylate and bovine amniotic membrane to repair perforated lesions in corneas. Penetrating keratoplasty was performed in sixty New Zealand White rabbits under general anesthesia. Group 1 (G1) was treated with n-butyl 2-cyanoacrylate, group 2 (G2) received a fragment of amniotic membrane through the anterior chamber and application of n-butyl 2-cyanoacrylate over the lesion, group 3 (G3) was treated with the same technique as G2 with the addition of an amniotic membrane bandage covering the cornea and sutured in the limbus region, and group 4 (G4) was treated with an amniotic membrane sutured to the lesion and an amniotic membrane bandage sutured in the limbus region. Clinical, histological and histomorphometric examinations of the corneas were performed. The membrane acted as a barrier for aqueous humor in G2 and G3, thereby keeping the surface dry for adhesive application; it also prevented the adhesive from contacting intraocular structures. The groups treated with amniotic membrane and surgical adhesive showed better results than the groups treated with either material alone. Thus, the combination of the membrane with the adhesive is recommended for this type of lesion...

Os objetivos deste estudo foram comparar técnicas cirúrgicas e efeitos do n-butil 2-cianoacrilato e da membrana amniótica bovina na reparação de lesões perfuradas em córneas. Sessenta coelhos da raça Nova Zelândia Branca foram submetidos à ceratoplastia penetrante sob anestesia geral. O grupo 1 (G1) foi tratado com n-butil 2-cianoacrilato; o grupo 2 (G2) recebeu um fragmento de membrana amniótica pela câmara anterior e aplicação de n-butil 2-cianoacrilato sobre a lesão; o grupo 3 (G3) foi tratado com a mesma técnica aplicada ao G2, adicionando-se uma bandagem de membrana amniótica cobrindo a córnea e suturada à região do limbo; e o grupo 4 (G4) foi tratado com membrana amniótica suturada nas bordas da lesão e bandagem de membrana amniótica suturada na região do limbo. Foram realizados exames clínico, histológico e histomorfométrico. A membrana atuou como barreira contra o extravasamento do humor aquoso nos grupos 2 e 3, manteve a superfície seca para posterior aplicação do adesivo e impediu o contato do adesivo com as estruturas intraoculares. Os grupos tratados com o adesivo associado à membrana amniótica demonstraram melhores resultados do que aqueles tratados com cada material isoladamente. Assim, a combinação da membrana com o adesivo é indicada neste tipo de lesão...