A energia ultra-sônica é um dos recursos físicos amplamente utilizado e pesquisado nos tratamentos de fisioterapia e diagnósticos médicos. Sabe-se que diante de uma escassa literatura dos efeitos do ultra-som em tecidos sadios, muitos profissionais fisioterapeutas acabam realizando aplicações infundadas de métodos e parâmetros. O objetivo desta pesquisa foi avaliar possíveis alterações do tecido sadio in vivo de ratos Wistar irradiados com diferentes intensidades, analisando a histologia e morfometria. Foram utilizados 30 ratos da linhagem Wistar, distribuídos aleatoriamente em 5 grupos de 6 animais cada. Foi escolhida a região dorsal do lado direito para tratamento com área de 4 \'CM POT.2\'. O lado esquerdo serviu como controle em todos os grupos. O tratamento foi feito durante 4 dias com 2 minutos de irradiação. Para verificar a intensidade de saída, utilizou-se o dosímetro de precisão antes da aplicação do ultra-som em cada animal. Foi realizada uma análise histológica descritiva e morfometria por meio do software Image Tool. Como resultado pode-se observar um discreto infiltrado inflamatório e adelgaçamento das fibras da derme, principalmente dos grupos irradiados com 1.5 e 2 W/\'CM POT.2\'. Notou-se também um aumento na espessura da epiderme nas amostras dos animais irradiados quando comparado com o controle. Para avaliar os resultados quantitativos, utilizou-se como análise estatística ANOVA \"one way\" e o teste \"pos hoc\" de Tukey com nível de significância p < 0,01. Em 120 medidas da espessura da epiderme obtiveram-se diferenças significativas do grupo controle com os grupos irradiados com (1.0, 1.5 e 2.0 W/\'CM POT.2\'). Concluímos diante dos resultados que houve alterações no tecido sob ação do US nas doses maiores, o que nos alerta para possíveis implicações do uso do US em estética. / The ultrasound (US) energy is one of the resources widely used and researched in both physio-therapist treatment and in medical diagnosis. In front of a scarce literature about the US effects in healthy tissues, many professionals have carried out unfounded applications of methods and parameters. So, the aim of this research was evaluate, through the histology, possible alternations in healthy tissues of Wistar rats in vivo irradiated with different intensity, analyzing the qualitative and quantitative histological slides. We used 30 Wistar rats randomly distributed in 5 groups of animals each. The local chosen for receiving the treatment was the dorsal right side, whose area was 4 \'CM POT.2\'. The left side was used as control of the animal itself for all the groups. The rats underwent the treatment during 4 days exposed to 2 minutes of irradiation. In order to check the energy output, the precision dosimeter was used before US application in each animal. The histological slides were evaluated qualitatively in the microscope and quantitatively through the image tool software. The qualitative result shows a discrete inflammatory process with infiltration and atrophy dermis fibers, mainly in the groups with higher US dosage. In the quantitative aspect, we found epidermis thickness increased in the 1.5 and 2 W/\'CM POT.2\' of US, with statistical difference (ANOVA) compared to control. We conclude that US therapy can be dangerous with high dosage applied in the intact skin.

Tendon injuries are prevalent, debilitating and difficult to treat. Common interventions such as anti-inflammatory medication, growth factor injections and surgery are associated with short-term efficacy and long rehabilitation periods. Tendons possess an incomplete healing response which is reparative (scar-mediated) rather than regenerative, resulting in a 'healed' tissue that is mechanically inferior to the native tendon. While it is widely accepted that mechanical-loading based treatments offer long-term symptomatic resolution and improved functionality, the exact mechanisms of action of such mechanotransduction-based healing cascades remain unclear. Nevertheless, there is significant motivation for the development of non-invasive and efficient rehabilitative treatments that mechanically stimulate the injured tendons to achieve functional healing responses. Focused Ultrasound (FUS) methods are an attractive treatment option as they are non-invasive, utilize higher intensities for shorter durations and are targeted to a very specific treatment volume, hence inducing significant bio-effects in the tissue without affecting surrounding structures. Herein, we present a body of work that includes the development of FUS pulsing to precisely target murine Achilles tendons and emphasize distinct bioeffects (thermal-dominant and mechanical-dominant). We investigated the feasibility of applying FUS pulsing to murine Achilles tendons ex vivo and in vivo and demonstrated that FUS can be safely applied without any deleterious effects in the tendons and surrounding tissues. The animals showed no symptoms of distress after multi-session treatments. Overall, results suggest that tendon material properties are not adversely altered by FUS pulsing. Histological analyses showed mild matrix disorganization, suggesting the need for slight modifications in the ultrasound pulsing parameters and treatment durations. When applied to injured tendons, mechanical dominant schemes seemed to drive larger improvements in material properties compared to thermal-dominant pulsing, confirming our original hypothesis that mechanical stimulation may play a bigger role in tendon healing compared to purely thermal-dominant stimulation. Additionally, feasibility of histotripsy ablation in murine Achilles tendons was successfully investigated ex vivo and in vivo and experimentation to further optimize these methods are ongoing. Such (non-thermal) ablative paradigms will be extremely useful when conservative treatment options are unavailable and debridement of scar tissue is warranted to interrupt the degenerative process and stimulate healing. Finally, a pilot investigation into FUS-induced strains was performed to guide our parameter selection process and deliver controlled strains to achieve healing responses (similar to current clinical rehabilitation protocols). We were able confirm that strains between 1% and 6% (or higher) can be induced by manipulating ultrasound treatment parameters. Overall, or results reiterate the potential of FUS in eliciting the desired bioeffects and thus achieve healing in tendons and provide a snapshot of the expected effects of using such pulsing methods to treat tendon injuries. / Doctor of Philosophy / Tendons are tissues that connect muscles to bones, and are unfortunately prone to injuries. Such injuries are prevalent and difficult to treat. Effective treatment options remain limited, as common methods such as surgery, anti-inflammatory medications and corticosteroid injections do not provide long-term relief. One of the few treatments that has been proven to provide symptomatic relief and improved the functionality of chronically (over a long period of time) injured tendons is physical therapy. However, researchers are still investigating the reasons for this successful healing response. Some limitations of physical therapy are long rehabilitation and recovery periods, and the need for patient compliance (i.e., performing painful exercises while already being under significant pain). In this research, we explore the use of a non-invasive modality known as ultrasound to treat tendon injuries. Ultrasound is commonly thought of as a diagnostic tool, i.e., to detect injuries in musculoskeletal medicine. It, however, is also an attractive therapeutic (treatment) modality, as sound waves can be concentrated in the required area of interest which results in different types of effects in the chosen tissue, such as heating. A huge advantage is that ultrasound is non-invasive, painless, and safe, as the energy is only applied to the chosen volume of interest and surrounding structures are unaffected. To examine the utility of therapeutic ultrasound in treating tendon injuries, we used a mouse model that has been previously used in our lab, and designed different types of ultrasound treatments that elicit two main types of effects in the tissue, namely, thermal, or heating effects and mechanical, or physical therapy-like effects. Prior to applying these treatments, we measured how much heating is produced in mouse Achilles tendons via these treatments, to establish safety. Once we identified safe thermal and mechanical treatment sets, we treated mouse Achilles tendons ex vivo, i.e., after euthanasia. We tested the mechanical properties of the treated tendons and determined that treatments do not alter the mechanical properties of tendons, which is encouraging, given that we do not want treatments to interfere with the properties of native tendons. We also examined the influence of treatments on structure of Achilles tendons after treatments and deducted that the structure was not damaged due to treatments. We followed up these studies with treatments conducted in live mice, which received four treatment sessions in one week. These studies were conducted to further determine the safety and tolerance to these procedures and also examine the healing effects of treatments in injured Achilles tendons. Results suggest that focused ultrasound treatments are safe and tolerable to mice and seem to elicit improvements in tendon properties. In other studies, we also examined a different ultrasound method named histotripsy, as a non-invasive alternative to dry needling (which is another methodology used to treat tendon injuries) and scar debridement (removal of scar tissue to stimulate a new healing response). This research establishes that therapeutic ultrasound is a novel, non-invasive alternative with good potential to treat tendon injuries. Future studies will investigate the effects of ultrasound treatments over longer durations and also aim to clarify the exact type and magnitude of physical therapy-like forces that are produced by ultrasound treatments. This understanding will enhance our treatment design process to be able to mimic clinical treatments that are known to be effective.

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O ultra-som terapêutico é um recurso físico muito empregado como coadjuvante na promoção do reparo tecidual. Neste trabalho, foi estudada a influência do ultra-som terapêutico na integração dos enxertos de pele total num modelo experimental em coelhos. Foram utilizados 20 coelhos adultos, fêmeas, nos quais foram realizadas cirurgias de enxerto autógeno de pele total nas regiões escapulares, pela ressecção de dois retalhos quadrados de pele de 2 cm de lado, invertendo sua posição, o enxerto retirado do lado direito sendo colocado na área receptora esquerda e vice-versa. O enxerto do lado direito era submetido ao tratamento efetivo com o ultra-som (3 MHz, 0,5 W/cm2, 5 minutos) e o enxerto do lado esquerdo, a tratamento placebo, iniciado no 3o dia pós-operatório e aplicado diariamente por sete dias. Os animais eram sacrificados no 11o dia pós-operatório e os enxertos, ressecados com uma margem de segurança, para análise histopatológica, com cortes de 5 µm. Foram obtidos cortes histológicos corados com técnicas específicas (Tricrômico de Gomori, PCNA e Picrosirius) e analisados ao microscópio de luz, sendo realizada a contagem das células em proliferação e dos vasos neoformados e a morfometria das áreas da epiderme e derme. Os resultados mostraram um significativo aumento no número de células em proliferação na epiderme e vasos neoformados na camada reticular da derme, mas isto não implicou em uma diferença entre as áreas da epiderme e derme, nos enxertos irradiados e não irradiados. Concluímos que o ultra-som terapêutico induz alterações morfológicas nos processos biológicos, como proliferação celular da camada germinativa da epiderme e neoangiogênese, envolvidos na integração de enxertos de pele total, com um potencial de aplicação clínica em humanos. / Therapeutic ultrasound is a widely used co-adjuvant physical mean to promote tissue repair. In the present investigation, the influence of therapeutic ultrasound on the integration of full-thickness skin graft was studied in rabbits. Twenty female adult rabbits were used, two 2x2 cm square-shaped full-thickness skin grafts being obtained from both scapular regions and swapped, the one cut out on the right being placed on the left and vice-versa. The graft on the right was effectively irradiated with the therapeutic ultrasound (3 MHz, 0,5 W/cm2, 5 minutes) for seven days beginning on the third postoperative day. The graft on the left was submitted to a sham irradiation. The animals were killed on the 11th day and the grafted areas were resected (graft + safety margin) for histologic examination by means of 5 µm-thick sections alternatively stained with Gomori's trichrome, PCNA and Picrosirius and examined on the light microscope. Eider proliferating cells and new blood vessels were counted, as well as the epidermic and dermic areas were measured. The results showed a significant increase in the number of epidermic proliferating cells and new blood vessels, but this did not imply any difference between the epidermic and dermic areas between irradiated and non-irradiated grafts. We conclude that the therapeutic ultrasound induces morphologic alterations in the biologic processes, as epidermic germinative layer cell proliferation and neo-angiogenesis, involved in the integration of full-thickness skin grafts and this has a potential for clinical use in humans.

Submitted by TATIANA EMY KOIKE null (tatikoike@yahoo.com) on 2016-03-10T11:09:02Z No. of bitstreams: 1 Encadernaçao Mestrado UNESP- Tatiana Emy Koike.pdf: 1535953 bytes, checksum: 25ca75a268f1c6bf7d7ca80e833b9cbd (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-03-10T20:19:49Z (GMT) No. of bitstreams: 1 koike_te_me_prud.pdf: 1535953 bytes, checksum: 25ca75a268f1c6bf7d7ca80e833b9cbd (MD5) / Made available in DSpace on 2016-03-10T20:19:49Z (GMT). No. of bitstreams: 1 koike_te_me_prud.pdf: 1535953 bytes, checksum: 25ca75a268f1c6bf7d7ca80e833b9cbd (MD5) Previous issue date: 2016-02-17 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Muscle injuries are often cause due to the practice of sports and recreational activities. Because of its high incidence, it is important to research the treatments that promote quality in the muscle and shorter repair process. To evaluate the effect of the combination of the therapeutic resources of Cryotherapy and Therapeutic Ultrasound in the treatment of muscle damage by impact. 55 Wistar rats was separate into groups, Acute Injury (AI), Injury (I), Cryotherapy (CR), Therapeutic Ultrasound (TU), Cryotherapy and Therapeutic Ultrasound (CRTU). All animals were anesthetize and muscle damage due to impact by the release of a load of 200 g at 30 cm. Then received treatments as allocated group and CR protocol using ice bag for 20 minutes and TU for five minutes with an intensity of 0.5W / cm2 and the frequency of 1MHz. Euthanasia was performed by intraperitoneal administration of overdose of Xylazine and Ketamine. The collection of the gastrocnemius muscle for the Body and Muscle mass analysis, histological analysis and fractal dimension of inflammation and collagen gene quantification of mRNA (TNF-α and TGF-β1). Data analysis was performed using SPSS for Windows 22. The Shapiro-Wilk test to verify the normality of the data was performed. When data showed normal, we used t test for paired samples test and one-way ANOVA followed by Tukey’s post-test. When it violated the normality of the data, followed by the Kruskal- Wallis test with Dunn’s post-test. For all analyzes was adopted the significance level of 5%. Among all groups, the CRTU lose less body and muscle mass, improved morphometry, besides presenting collagen reduction by DF compared to AI and CR (p <0.05). With regard to the inflammatory process CRTU group showed a significant reduction of DF in relation to the AI groups (p = 0.001), I (p = 0.001) and CR (p = 0.007), and TU reduced the DF significantly relative to AI groups (p = 0.001), I (p = 0.001) and CR (p = 0.036). The reduction of TNF-α was significant in TU group compared with AI groups (p = 0.008); I (p = 0.032) and CR (p = 0.046) and TGF- β1 in the CR group compared to AI (p = 0.001) and I (p = 0.006), in the TU group compared to AI (p = 0.049) and CRTU compared to AI (p = 0.023). The combination treatment was superior to the results presented by the isolated treatments in the muscle repair process. Observed by reducing the loss of body and muscle mass, improved histological appearance and reduction of collagen. / As lesões musculares são frequentemente ocasionadas em decorrência da prática de atividades esportivas e recreativas. Devido sua alta incidência, é importante pesquisar os tratamentos que promovam qualidade no processo de reparação muscular e menor duração. Avaliar o efeito da combinação dos recursos terapêuticos de Crioterapia e Ultrassom Terapêutico no tratamento de lesão muscular por impacto. 55 ratos wistar foram separados em Grupos Lesão Aguda (LA), Lesão (L), Crioterapia (CR), Ultrassom Terapêutico (US), Crioterapia e Ultrassom Terapêutico (CRUS). Todos os animais foram anestesiados e submetidos à lesão muscular por impacto pela liberação de uma carga de 200g a 30 cm de altura. Em seguida receberam os tratamentos conforme grupo alocado, sendo o protocolo de CR por meio de bolsa de gelo durante 20 minutos e o US durante cinco minutos com intensidade de 0,5W/cm2 e frequência de 1MHz. A eutanásia foi realizada por administração intraperitoneal de superdosagem de Xilazina e Ketamina, para subsequente coleta do músculo gastrocnêmio destinado às análises de massa Corporal e Muscular, análises Histológica e Dimensão Fractal do processo inflamatório e de colágeno, Quantificação gênica de RNAm (TNF-α e TGF-β1). A análise dos dados foi realizada utilizando o programa estatístico SPSS 22 for Windows. Foi realizado o teste de Shapiro-Wilk para verificação da normalidade dos dados. Quando os dados apresentaram normalidade, foi utilizado teste T para amostras pareadas e teste de Anova one-way, seguido pelo pós-teste de Tukey. Quando violada a normalidade dos dados, seguiu-se com o teste de Kruskall-Wallis, com pós-teste de Dunn. Para todas as análises foi adotado o nível de significância de 5%. Dentre todos os grupos, o CRUS perdeu menos massa corporal e muscular, melhora da morfometria, além de apresentar redução de colágeno pela DF em comparação aos LA e CR (p < 0,05). Com relação ao processo inflamatório, grupo CRUS apresentou redução significante da DF em relação aos grupos LA (p = 0,001), L (p = 0,001) e CR (p = 0,007), e o US reduziu a DF significativamente em relação aos grupos LA (p = 0,001), L (p = 0,001) e CR (p = 0,036). A redução de TNF-α foi significante no grupo US comparado com grupos LA (p = 0,008); L (p = 0,032) e CR (p = 0,046), e TGF-β1 no grupo CR em comparação aos LA (p = 0,001) e L (p = 0,006), no grupo US em comparação ao LA (p = 0,049), e CRUS em comparação aos LA (p = 0,023). A associação de tratamentos foi superior aos resultados apresentados pelos tratamentos isolados no processo de reparação muscular. Observado pela redução da perda de massa corporal e muscular, melhora do aspecto histológico e redução de colágeno.

Submitted by Maryse Santos (maryseeu4@gmail.com) on 2016-09-02T14:50:49Z No. of bitstreams: 1 Dissertação de Mestrado- Lílian Regiani Merini.pdf: 39821271 bytes, checksum: 7d2e1712bdc1b9a4052221560d2ffedf (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-09-16T12:35:27Z (GMT) No. of bitstreams: 1 Dissertação de Mestrado- Lílian Regiani Merini.pdf: 39821271 bytes, checksum: 7d2e1712bdc1b9a4052221560d2ffedf (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-09-16T12:40:51Z (GMT) No. of bitstreams: 1 Dissertação de Mestrado- Lílian Regiani Merini.pdf: 39821271 bytes, checksum: 7d2e1712bdc1b9a4052221560d2ffedf (MD5) / Made available in DSpace on 2016-09-16T12:40:51Z (GMT). No. of bitstreams: 1 Dissertação de Mestrado- Lílian Regiani Merini.pdf: 39821271 bytes, checksum: 7d2e1712bdc1b9a4052221560d2ffedf (MD5) Previous issue date: 2012-07-30 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Physiotherapy uses phonophoresis to treat many diseases that affect the body and aims to relieve pain symptoms and improve functional capacity. Many native species from the Amazon are studied for topical application to human health. Some species show antirheumatic, antibacterial and antifungal actions. Considering the biological potential of Elaeoluma nuda in in vitro studies, this study evaluated the effect of the gel prepared with the extract of Elaeoluma nuda by phonophoresis on Adjuvant-Induced Arthritis in Lewis rats. The animals used herein were divided into: Group I: negative control - no induction and no treatment (n = 6), group II: positive control - with induction and without treatment (n = 6). Group III: induction and exposed to the therapeutic ultrasound treatment with conductive gel (n = 6) Group IV: induction and exposed to treatment by phonophoresis and gel of Elaeoluma nuda (n = 6) Group V: induction and exposed to the treatment by phonophoresis gel of diclophenac (n = 6). The antiedematogenic and anti-inflammatory effect were analyzed by pletismometria and flow cytometry. The effect of the aqueous gel of Elaeoluma nuda by phonophoresis on arthritis of the hind paw of rats was equivalent to diclophenac gel phonophoresis dietilomônio compared to positive control (p = 0.002), with reduction of arthritis in 33%. The therapeutic ultrasound without phonophoresis showed no significant effect until the 21st day of the experiment with only 2% attenuation of the arthritis. There were significant decreased levels of TNF-α and IL1-β (p = 0.0398 and p = 0.0278, respectively) for the group treated by phonophoresis with gel of E. nuda. The profile of the signature of high cytokines producers treated by gel of E. nuda was similar to as the negative control group while the group treated with therapeutic ultrasound showed a similar profile to the positive control. The results demonstrate the anti-inflammatory effects of the gel of E. nuda by phonophoresis on arthritis adjuvant-induced. / A Fisioterapia usa a fonoforese para tratar inúmeras doenças que afetam o organismo objetivando aliviar sintomas álgicos e melhorar capacidade funcional. Muitas espécies nativas da Amazônia são estudadas para aplicação tópica na saúde humana. Algumas espécies demonstram ação antireumática, antibacteriana e antifúngica. Considerando o potencial biológico da Elaeoluma nuda em pesquisas in vitro, este estudo objetivou avaliar a ação do gel preparado à base de extrato de Elaeoluma nuda pela fonoforese sobre Artrite Induzida por Adjuvante em ratos Lewis. Foram utilizados animais, divididos em: Grupo I: controle negativo – sem indução e sem tratamento (n=6), Grupo II: controle positivo – com indução e sem tratamento (n=6). Grupo III: com indução e expostos ao tratamento com UST com gel condutor (n=6), Grupo IV: com indução e exposto ao tratamento pela fonoferese com gel de Elaeoluma nuda (n=6) Grupo V: com indução e expostos ao tratamento pela fonoforese com gel de diclofenaco (n=6). O efeito antiedematogênico e antiinflamatório nos grupos foram analisados por pletismometria e citometria de fluxo.O efeito da fonoforese com gel aquoso de E. nuda sobre a artrite da pata de ratos, foi equivalente à fonoforese com gel de diclofenaco dietilomônio quando comparados ao controle positivo (p=0.002), com redução da artrite em 33%. O ultrassom terapêutico sem fonoforese não mostrou efeito significativo até o 21º. dia de experimento com atenuação de artrite de apenas 2%. Houve redução siginificativa dos níveis deTNF-α e IL1-β com p=0.0398 e p=0.0278, respectivamente, para grupo tratado com fonoforese e gel de E. nuda. O perfil da assinatura de altos produtores de citocinas tratados com gel de E. nuda foi semelhante ao controle negativo enquanto o grupo tratado apenas com UST apresentou perfil semelhante ao controle positivo. Os resultados demonstram o efeito anti-inflamatório da fonoforese com gel de E. nuda sobre a artrite induzida por adjuvante.

O ultra-som terapêutico é um recurso físico muito empregado como coadjuvante na promoção do reparo tecidual. Neste trabalho, foi estudada a influência do ultra-som terapêutico na integração dos enxertos de pele total num modelo experimental em coelhos. Foram utilizados 20 coelhos adultos, fêmeas, nos quais foram realizadas cirurgias de enxerto autógeno de pele total nas regiões escapulares, pela ressecção de dois retalhos quadrados de pele de 2 cm de lado, invertendo sua posição, o enxerto retirado do lado direito sendo colocado na área receptora esquerda e vice-versa. O enxerto do lado direito era submetido ao tratamento efetivo com o ultra-som (3 MHz, 0,5 W/cm2, 5 minutos) e o enxerto do lado esquerdo, a tratamento placebo, iniciado no 3o dia pós-operatório e aplicado diariamente por sete dias. Os animais eram sacrificados no 11o dia pós-operatório e os enxertos, ressecados com uma margem de segurança, para análise histopatológica, com cortes de 5 µm. Foram obtidos cortes histológicos corados com técnicas específicas (Tricrômico de Gomori, PCNA e Picrosirius) e analisados ao microscópio de luz, sendo realizada a contagem das células em proliferação e dos vasos neoformados e a morfometria das áreas da epiderme e derme. Os resultados mostraram um significativo aumento no número de células em proliferação na epiderme e vasos neoformados na camada reticular da derme, mas isto não implicou em uma diferença entre as áreas da epiderme e derme, nos enxertos irradiados e não irradiados. Concluímos que o ultra-som terapêutico induz alterações morfológicas nos processos biológicos, como proliferação celular da camada germinativa da epiderme e neoangiogênese, envolvidos na integração de enxertos de pele total, com um potencial de aplicação clínica em humanos. / Therapeutic ultrasound is a widely used co-adjuvant physical mean to promote tissue repair. In the present investigation, the influence of therapeutic ultrasound on the integration of full-thickness skin graft was studied in rabbits. Twenty female adult rabbits were used, two 2x2 cm square-shaped full-thickness skin grafts being obtained from both scapular regions and swapped, the one cut out on the right being placed on the left and vice-versa. The graft on the right was effectively irradiated with the therapeutic ultrasound (3 MHz, 0,5 W/cm2, 5 minutes) for seven days beginning on the third postoperative day. The graft on the left was submitted to a sham irradiation. The animals were killed on the 11th day and the grafted areas were resected (graft + safety margin) for histologic examination by means of 5 µm-thick sections alternatively stained with Gomori's trichrome, PCNA and Picrosirius and examined on the light microscope. Eider proliferating cells and new blood vessels were counted, as well as the epidermic and dermic areas were measured. The results showed a significant increase in the number of epidermic proliferating cells and new blood vessels, but this did not imply any difference between the epidermic and dermic areas between irradiated and non-irradiated grafts. We conclude that the therapeutic ultrasound induces morphologic alterations in the biologic processes, as epidermic germinative layer cell proliferation and neo-angiogenesis, involved in the integration of full-thickness skin grafts and this has a potential for clinical use in humans.

A influência do ultra-som terapêutico na transmissão transcutânea (sonoforese) do diclofenaco sódico como gel tópico (Voltaren Emulgel) foi investigada em 14 voluntários humanos sadios (dez mulheres, quatro homens; 26,4 anos de idade, 62 Kg de peso corporal e 1,7 m de altura, em média). Foi realizada irradiação ultra-sônica prévia da pele (modo contínuo, 1 MHz de freqüência, intensidade de 0,5 W/centímetro quadrado) por 5 minutos em duas áreas de 225 centímetros quadrados (15 x 15 cm) de cada lado da região dorsal dos voluntários usando um gel comum para acoplamento do cabeçote, com subseqüente aplicação do gel de diclofenaco (2,5 g) em cada uma das áreas pré-determinadas e deixado por três horas. Os mesmos voluntários participaram desse procedimento duas vezes com um mês de intervalo, em média, sendo que na segunda vez com o equipamento desligado (procedimento placebo), para controle. Amostras de sangue (3 ml) foram coletadas de veias do antebraço imediatamente antes e com 60, 120 e 180 minutos do procedimento, para análise da massa plasmática do diclofenaco, por meio da cromatografia líquida de alta eficiência (HPLC). Os resultados demonstraram que a massa plasmática do diclofenaco estava significativamente mais elevada (p=0,01) aos 60 e 120 minutos após a irradiação com o ultra-som do que após o procedimento placebo. Dentro das condições em que este estudo foi realizado, os resultados permitem concluir que a irradiação prévia da pele com ultra-som terapêutico facilita a penetração transcutânea de diclofenaco sódico na forma de gel tópico / The influence of therapeutic ultrasound on the transdermal transmission (sonophoresis) of sodium diclofenac as a gel of topic application (Voltaren Emulgel) was investigated in 14 human healthy volunteers (ten women, four men, 26,4 years of age, 62 Kg of body weight and 1,7 m of height on average). Therapeutic ultrasound (continuous mode, 1 MHz frequency, 0,5 W/square centimeter) was applied for 5 minutes on two 225 square centimeters (15 x 15 cm) areas on each side of the dorsum of the volunteers using ultrasound transmission gel as a coupling agent. Following ultrasonic irradiation, the gel was removed and gloves were used to apply 2,5 g on each two defined areas. The same volunteers participated in procedures twice at one-month interval on average, however the second time with the equipment turned off (sham procedure) for control. Blood samples (3 ml) were withdrawn from forearm veins, near the elbow flexure, immediately before and at 60, 120 and 180 minutes from the procedure, for analysis of the plasmatic diclofenac mass by means of high performance liquid chromatography (HPLC). The results showed that the plasmatic diclofenac mass was significantly higher (p=0,01) at 60 and 120 minutes following the ultrasound irradiation than the sham procedure. The results presented in this study support that therapeutic ultrasound applied prior to application of sodium diclofenac gel does lead to enhanced penetration of the drug across the skin under the conditions of the investigation

O objetivo do presente trabalho foi de analisar, experimentalmente, a variação do índice de transmissão e o coeficiente de atenuação ultra-sônica no meio diclofenaco gel, bem como, a penetração do fármaco em amostras de gelatina semelhante a pele humana através da fonoforese. A variação destes parâmetros foi investigada em 120 amostras de agar-agar, (modo contínuo, 1 MHz de freqüência, nas intensidades de 1,0 e 1,5 W/\'CM POT.2\'), por 5 minutos. Os corpos de prova forma divididos em grupos referentes as intensidades de ultra-som utilizadas, e cada um destes grupos, foi subdividido em sub-grupos correspondendo aos diferentes meios utilizados para irradiação. A investigação da transmissão ultra-sônica foi medida a partir de um dosímetro de precisão ULTRASONIC POWER METER, modelo UPM-DT 10. O cálculo do coeficiente de atenuação foi realizado a partir dos dados de leitura da transmissão ultra-sônica. A penetração ou não da droga foi estudada por análise macroscópica e microscópica. Segundo os resultados obtidos não houve variação significativa nos índices de transmissão e nos coeficientes de atenuação do diclofenaco gel em comparação ao gel neutro. A penetração do medicamento foi de 3 mm para as amostras irradiadas com a intensidade de 1,0 W/\'CM POT.2\' e de 5 mm para as amostras irradiadas com 1,5 W/\'CM POT.2\', não houve evidência de penetração do fármaco no grupo controle. Os resultados obtidos neste estudo sugerem que a fonoforese do diclofenaco gel é efetiva nas intensidades 1,0 e 1,5 W/\'CM POT.2\'. / The objective of the present work was of analyzing, experimentally, the variation of the transmission index and the coefficient of ultrasonic reduction in the half diclofenaco gel, as well as, the penetration of the drug in samples of similar jelly the human skin through the phonophoresis. The variation of these parameters was investigated in 120 agar-agar samples, (continuous way, 1 MHz of frequency, in the intensities of 1,0 and 1,5 W/\'CM POT.2\'), for 5 minutes. The proof bodies form divided in referring groups the ultrasound intensities used, and each one of these groups, it was subdivided in sub-groups corresponding to the different means used for irradiation. The investigation of the ultrasonic transmission was measured starting from a ULTRASONIC POWER METER, model UPM-DT 10. The calculate it of the reduction coefficient was accomplished starting from the data of reading of the ultrasonic transmission. The penetration or not of the drug it was studied for it analyzes macroscopic and microscopic. According to the obtained results there was not significant variation in the transmission indexes and in the coefficients of reduction of the diclofenaco gel in comparison with the neutral gel. The penetration of the medicine went of 3 mm to the samples irradiated with the intensity of 1,0 W/\'CM POT.2\' and of 5 mm for the samples irradiated with 1,5 W/\'CM POT.2\', there was not evidences of penetration of the drug in the group control. The results obtained in this study suggest that the phonophoresis of the diclofenaco gel is effective in the intensities 1,0 and 1,5 W/\'CM POT.2\'.