Poly(ethylene terephthalate) was depolymerised under supercritical ethanol, 98 wt% of diethylterephthalate was obtained after 45 min, by adding [Bmim][BF4] as catalyst.

The marine snail peptide ziconotide (x-conotoxin MVIIA) is used as an analgesic in cancer patients refractory to opioids, but may induce severe adverse effects. Animal venoms represent a rich source of novel drugs, so we investigated the analgesic effects and the side-effects of spider peptide Pha1b in a model of cancer pain in mice with or without tolerance to morphine analgesia. Cancer pain was induced by the inoculation of melanoma B16-F10 cells into the hind paw of C57BL ⁄ 6 mice. After 14 days, painful hypersensitivity was detected and Pha1b or x-conotoxin MVIIA (10-100 pmol ⁄ site) was intrathecally injected to evaluate the development of antinociception and side-effects in control and morphine-tolerant mice. The treatment with Pha1b or x-conotoxin MVIIA fully reversed cancer-related painful hypersensitivity, with long-lasting results, at effective doses 50% of 48 (32-72) or 33 (21-53) pmol ⁄ site, respectively. Pha1b produced only mild adverse effects, whereas x-conotoxin MVIIA induced dose-related side-effects in mice at analgesic doses (estimated toxic dose 50% of 30 pmol ⁄ site). In addition, we observed that Pha1b was capable of controlling cancer-related pain even in mice tolerant to morphine antinociception (100% of inhibition) and was able to partially restore morphine analgesia in such animals (56 AE 5% of inhibition). In this study, Pha1b was as efficacious as x-conotoxin MVIIA in inducing analgesia in a model of cancer pain without producing severe adverse effects or losing efficacy in opioid-tolerant mice, indicating that Pha1b has a good profile for the treatment of cancer pain in patients. (Cancer Sci 2013; 104: 1226-1230

The transient receptor potential vanilloid 1 (TRPV1) receptor is relevant to the perception of noxious information and has been studied as a therapeutic target for the development of new analgesics. The goal of this study was to perform in vivo and in vitro screens to identify novel, efficacious, and safe TRPV1 antagonists isolated from leaves of the medicinal plant Vernonia tweedieana Baker. All of the fractions and the hydroalcoholic extract produced antinociception in mice during the capsaicin test, but the dichloromethane fraction also had antioedematogenic effect. Among the compounds isolated from the dichloromethane fraction, only ␣-spinasterol reduced the nociception and edema induced by capsaicin injection. Moreover, ␣-spinasterol demonstrated good oral absorption and high penetration into the brain and spinal cord of mice. ␣-Spinasterol was able to displace [ 3 H]resiniferatoxin binding and diminish calcium influx mediated by capsaicin. Oral administration of the dichloromethane fraction and ␣-spinasterol also produced antinociceptive effect in the noxious heat-induced nociception test; however, they did not change the mechanical threshold of naive mice. The treatment with ␣-spinasterol did not produce antinociceptive effect in mice systemically pretreated with resiniferatoxin. In addition, ␣-spinasterol and the dichloromethane fraction reduced the edema, mechanical, and heat hyperalgesia elicited by complete Freund's adjuvant paw injection. The dichloromethane fraction and ␣-spinasterol did not affect body temperature or locomotor activity. In conclusion, ␣-spinasterol is a novel efficacious and safe antagonist of the TRPV1 receptor with antinociceptive effect.

The transient receptor potential ankyrin 1 (TRPA1) has been identified as a relevant target for the development of novel analgesics. Gallic acid (GA) is a polyphenolic compound commonly found in green tea and various berries and possesses a wide range of biological activities. The goal of this study was to identify GA as a TRPA1 antagonist and observe its antinociceptive effects in different pain models. First, we evaluated the ability of GA to affect cinnamaldehyde-induced calcium influx. Then, we observed the antinociceptive and antiedematogenic effects of GA (3-100 mg/kg) oral administration after the intraplantar (i.pl.) injection of TRPA1 agonists (allyl isothiocyanate, cinnamaldehyde, or hydrogen peroxide-H2O2) in either an inflammatory pain model (carrageenan i.pl. injection) or a neuropathic pain model (chronic constriction injury) in male Swiss mice (25-35 g). GA reduced the calcium influx mediated by TRPA1 activation. Moreover, the oral administration of GA decreased the spontaneous nociception triggered by allyl isothiocyanate, cinnamaldehyde, and H2O2. Carrageenan-induced allodynia and edema were largely reduced by the pretreatment with GA. Moreover, the administration of GA was also capable of decreasing cold and mechanical allodynia in a neuropathic pain model. Finally, GA was absorbed after oral administration and did not produce any detectable side effects. In conclusion, we found that GA is a TRPA1 antagonist with antinociceptive properties in relevant models of clinical pain without detectable side effects, which makes it a good candidate for the treatment of painful conditions.

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Pesq. Vet. Bras. 34(3):261-269, março 2014 261 RESUMO.-Sete casos de criptococose (seis gatos e um cão) foram estudados para estabelecer as características histomorfológicas e histoquímicas determinantes no diagnóstico histopatológico dessa condição. Os dados complementares relacionados à epidemiologia, aos aspectos clínicos, à localização das lesões e às alterações macroscópicas foram obtidos dos protocolos de necropsias e biópsias. Na histologia, as leveduras foram observadas no interior de macrófagos ou livres no parênquima, associadas à reação inflamatória linfo-histioplasmocítica que variou de escassa a acentuada. Pela técnica de hematoxilina-eosina (HE) as leveduras eram arredondadas, com célula central contendo um núcleo, circundada por um halo claro (cápsula geralmente não corada). As técnicas histoquímicas do ácido periódico de Schiff (PAS), Grocott e Fontana-Masson (FM) foram utilizadas e evidenciaram a parede das células das leveduras. Pelo FM observou-se a melanina presente nessas células. As téc- Seven cases of cryptococosis (six cats and one dog) were studied to establish the determining histomorphological and histochemical characteristics in the histopathological diagnosis of this condition. Additional data related to the epidemiology, clinical aspects, sites of the lesions, and gross findings were obtained from the necropsy and biopsy protocols. Histologically, yeasts were observed inside macrophages or free in the parenchyma, associated with scarse to severe lymphohistioplasmacytic inflammatory reaction. In the hematoxylin-eosin (HE) sections, the yeasts were round, with a central cell containing a nucleus, surrounded by a clear halo (usually non-stained capsule). The techniques of periodic Schiff acid (PAS), Groccot (GMS), and Fontana-Masson (FM) were utilized and demonstrated the wall of the yeast cells. The FM stain showed the melanin present in these cells. The Alcian blue and Mayer's mucicarmin stains showed mainly the yeast polysaccharide capsule. The diameter of the cells ranged from 1.67 to 10.00µm and the full diameter of the encapsulated yeasts varied between 4.17 e 34.16µm. Yeast buddings were better observed through the PAS stain and were narrow based, simple or multiple, mainly in the opposite poles of the cells or forming chains. The definitive diagnosis of cryptococosis was established through the histopathological exam, based on the specific morphology of the agent (encapsulated yeast) and on histochemical proprieties, mostly in the cases without fungal culture.

No abstract

[Hmim][HSO] ionic liquid (IL) and bio-renewable sources as chitosan (CHT) and chondroitin sulfate (CS) were used to yield hydrogel-based materials (CHT/CS). The use of IL to solubilize both polysaccharides was considered an innovative way based on "green chemistry" principle, aiming the production of CHT/CS blended systems. CHT/CS hydrogels were carried out in homogeneous medium from short dissolution times. The hydrogels were characterized and achieved with excellent stabilities (in the 1.2-10pH range), larger swelling capacities, as well as devoid of cytotoxicity towards the normal VERO and diseased HT29 cells. The CHT/CS hydrogels carried out in [Hmim][HSO] could be applied in many technological purposes, like medical, pharmaceutical, and environmental fields.