Metformin reduces c-Fos and ATF3 expression in the dorsal root ganglia and protects against oxaliplatin-induced peripheral sensory neuropathy in mice.

Oxaliplatin is a third-generation platinum drug commonly used as the first line treatment of metastatic colorectal cancer. Oxaliplatin-based anticancer regimens course with dose-limiting neurotoxicity. The pharmacological strategies used to manage such side effect are not totally effective. Metformin is an anti-diabetic drug that is described to negatively modulate painful diabetic neuropathy. Then, this study aimed to assess the effect of metformin in the oxaliplatin-induced peripheral sensory neuropathy in mice. For that purpose, Swiss male mice were injected with oxaliplatin (1, 2 or 4 mg/kg, i.v., twice a week with a total of nine injections) alone or in combination with daily administration of metformin (250 mg/kg, p.o.). Thermal and mechanical nociceptive tests were performed once a week for five weeks. Then, the animals were euthanized on day 35 post-first injection of oxaliplatin and the dorsal root ganglia were harvested for the assessment of c-Fos and ATF3 expressions. Oxaliplatin caused a nociceptive response accompanied by the increased expression of c-Fos and ATF3 in the dorsal root ganglia and spinal cord. In addition, the oxaliplatin-associated nociception was significantly attenuated by metformin (P < 0.05), which also reduced the expression of c-Fos and ATF3 (P < 0.05). Therefore, metformin protected from the peripheral sensory neuropathy induced by oxaliplatin, which was confirmed by the reduction of c-Fos and ATF3 expression, two known neuronal activation and damage markers, respectively.

Involvement of Endothelin Receptors in Peripheral Sensory Neuropathy Induced by Oxaliplatin in Mice.

The aim of this study was to evaluate the participation of the endothelin ETA and ETB receptors and the effects of bosentan in oxaliplatin-induced peripheral sensory neuropathy (OIN) in mice. Adult male Swiss mice received 1 mg/kg of oxaliplatin intravenously, twice a week for 5 weeks. Dorsal root ganglia (DRG) and spinal cords were removed for evaluation of the endothelin ETA and ETB receptor expression. Afterwards, selective (BQ-123 and BQ-788; 10 nmol in 30 µL, intraplantarly) and non-selective (bosentan, 100 mg/kg, orally) antagonists were administered in order to evaluate the involvement of the endothelin receptors in OIN. Mechanical and thermal nociception tests were performed once a week for 56 days. Oxaliplatin induced mechanical and thermal hypersensitivity and increased the endothelin ETA receptor expression in both the DRG and spinal cord (P < 0.05). Endothelin ETB receptor expression was increased in the DRG (P < 0.05) but not in the spinal cord. Both endothelin ETA and ETB receptor selective antagonists partially prevented mechanical hyperalgesia in mice with OIN (P < 0.05). Moreover, bosentan prevented mechanical and thermal hypersensitivity in oxaliplatin-treated mice (P < 0.05). In conclusion, both endothelin ETA and ETB receptors seem to be involved in the OIN in mice and they should be considered possible targets for the management of this clinical feature.

Fisioterapia dermatofuncional para glúteos com fibroedema gelóide: a importância da fonoforese / Dermatofunctional physiotherapy for buttocks with cellulite: the importance of phonophoresis

Introdução: Dentre os recursos da Fisioterapia Dermatofuncional para o tratamento do fibroedema gelóide (FEG) pode-se utilizar a endermologia e o ultrassom. Objetivo: Demonstrar a importância do uso da fonoforese como recurso fisioterápico dermatofuncional para tratamento do FEG. Métodos: Foi realizada uma pesquisa quantitativa e intervencionista em 16 mulheres, sendo do lado esquerdo utilizado fonoforese (com princí­pios ativos) e endermologia e do lado direito ultrassom com gel comum e endermologia por dez atendimentos no perí­odo de julho a dezembro de 2017. Resultados: Quanto ao perí­odo de surgimento do FEG 25% das pacientes relataram que surgiu devido ao ganho de peso; quanto í utilização de métodos contraceptivos 81,25% faziam uso; quanto aos hábitos alimentí­cios 56,25% possuí­am uma alimentação gordurosa diária; quanto í prática de atividade 81,25% eram sedentárias e com relação í forma clí­nica do FEG 50% apresentavam a forma flácida. Para o aspecto da pele observou-se a positividade dos resultados maior do lado esquerdo do que do direito. Conclusão: Foi demonstrada uma melhora da aparência geral da pele com redução das irregularidades bem como uma melhora do contorno da região glútea de todas as pacientes que concluí­ram o tratamento com maiores respostas do lado esquerdo no qual foi realizado a fonoforese. (AU)

Introduction: Among the resources of dermatofunctional physiotherapy for the treatment of cellulite, is possible to use endermology and ultrasound. Objective: To demonstrate the importance of phonophoresis as a dermatological and physical therapy resource for the treatment of cellulite. Methods: A quantitative and interventional study was carried out in 16 women. The left side used phonophoresis (with active principles) and endermology, and the ultrasound on the right side with common gel and endermology for ten consultations from July to December 2017. Results: Regarding the period of onset of cellulite 25% of the patients reported that it appeared due to weight gain; 81.25% used contraceptive methods; 56.25% had a daily fat diet; 81.25% were sedentary and in relation to the clinical form of the cellulite 50% presented the flaccid form. We observed better results on the left side than on the right. Conclusion: The general appearance of the skin improved with reduction of irregularities as well as the contour of the gluteal region of all the patients that concluded the treatment with better results of the left side in which the phonophoresis was applied. (AU)

Tratamento dermato-funcional para rugas com uso de blender químico e eletrolifting / Treatment of wrinkles using chemical blender and electrolifting

As rugas são alterações indesejáveis devido à modificação notecido cutâneo. Os objetivos dessa pesquisa foram comparar otratamento para rugas com uso de blender químico, eletrolifting e aassociação desses compostos e identificar os fototipos, os tipos depele e de rugas. Tratou-se de um estudo descritivo, intervencionistae comparativo. Foi realizado no Centro Universitário Christusno período de novembro de 2010 a maio de 2011. A amostra foicomposta por 30 mulheres com idade entre 30 e 55 anos, que foramatendidas individualmente, totalizando 300 atendimentos. Foramdivididas nos seguintes grupos: Grupo A (n = 10) que foi usado oblender químico composto por ácido hialurônico (pH: 3.5), vitaminaC e colágeno; Grupo B (n = 10) realizou-se uma escarificaçãocom microcorrente galvânica (300 μa) e o Grupo C (n = 10) noqual foram feitas ambas as condutas. Os fototipos encontrados nostrês grupos foram III e IV; quanto ao tipo de pele, predominou amista no grupo A, oleosa no grupo B e essas duas classificações nogrupo C; quanto ao tipo de rugas pode observar-se diminuição daquantidade de rugas profundas ao final do tratamento. Conclui-seque houve diminuição das rugas em número e profundidade sendomais evidente no grupo dos recursos associados.

Wrinkles are undesirable alterations in skin tissue. The objectivesof this research were to compare the treatment of wrinkles with theuse of chemical blender and electrolifting and the association ofboth products to identify skin phototypes, skin types and wrinkles.This was a descriptive, comparative and interventional study, held atChristus College from November 2010 to May 2011. The sampleconsisted of 30 women aged between 30 and 55 who were treatedindividually with a total of 300 treatment sessions in the followinggroups: Group A (n = 10) in which was used blender chemicalcompound of hyaluronic acid (pH: 3.5), vitamin C and collagen,Group B (n = 10) who held a scarification done with galvanic microcurrent(300 μa), and Group C (n = 10) where both treatmentswere conducted. The phototypes found in the three groups wereIII and IV; the type of skin was the mixed type predominating ingroup A, the oily type predominated in group B and both of thesein group C. It could be observed a decrease in the amount of deepwrinkles at the end of the treatment. It was concluded that there wasa decrease of number and deepness of wrinkles more important inthe group that used both chemical and electro blender treatments.