Intestinal FXR Activation via Transgenic Chimera or Chemical Agonism Prevents Colitis-Associated and Genetically-Induced Colon Cancer.

The Farnesoid X Receptor (FXR) is the master regulator of Bile Acids (BA) homeostasis orchestrating their synthesis, transport and metabolism. Disruption of BA regulation has been linked to gut-liver axis diseases such as colorectal cancer (CRC). In this study, firstly we examined the role of constitutive activation of intestinal FXR in CRC; then we pre-clinically investigated the therapeutic potential of a diet enriched with a synthetic FXR agonist in two models of CRC (chemically-induced and genetic models). We demonstrated that mice with intestinal constitutive FXR activation are protected from AOM/DSS-induced CRC with a significant reduction of tumor number compared to controls. Furthermore, we evaluated the role of chemical FXR agonism in a DSS model of colitis in wild type (WT) and FXRnull mice. WT mice administered with the FXR activating diet showed less morphological alterations and decreased inflammatory infiltrates compared to controls. The FXR activating diet also protected WT mice from AOM/DSS-induced CRC by reducing tumors' number and size. Finally, we proved that the FXR activating diet prevented spontaneous CRC in APCMin/+ mice via an FXR-dependent modulation of BA homeostasis. Our results demonstrate that intestinal FXR activation prevented both inflammation- and genetically-driven colorectal tumorigenesis by modulating BA pool size and composition. This could open new avenues for the therapeutic management of intestinal inflammation and tumorigenesis.

Reduction in gut-derived MUFAs via intestinal stearoyl-CoA desaturase 1 deletion drives susceptibility to NAFLD and hepatocarcinoma.

Nonalcoholic fatty liver disease (NAFLD) is defined by a set of hepatic conditions ranging from steatosis to steatohepatitis (NASH), characterized by inflammation and fibrosis, eventually predisposing to hepatocellular carcinoma (HCC). Together with fatty acids (FAs) originated from adipose lipolysis and hepatic lipogenesis, intestinal-derived FAs are major contributors of steatosis. However, the role of mono-unsaturated FAs (MUFAs) in NAFLD development is still debated. We previously established the intestinal capacity to produce MUFAs, but its consequences in hepatic functions are still unknown. Here, we aimed to determine the role of the intestinal MUFA-synthetizing enzyme stearoyl-CoA desaturase 1 (SCD1) in NAFLD. We used intestinal-specific Scd1-KO (iScd1-/- ) mice and studied hepatic dysfunction in different models of steatosis, NASH, and HCC. Intestinal-specific Scd1 deletion decreased hepatic MUFA proportion. Compared with controls, iScd1-/- mice displayed increased hepatic triglyceride accumulation and derangement in cholesterol homeostasis when fed a MUFA-deprived diet. Then, on Western diet feeding, iScd1-/- mice triggered inflammation and fibrosis compared with their wild-type littermates. Finally, intestinal-Scd1 deletion predisposed mice to liver cancer. Conclusions: Collectively, these results highlight the major importance of intestinal MUFA metabolism in maintaining hepatic functions and show that gut-derived MUFAs are protective from NASH and HCC.

Platelets from patients with visceral obesity promote colon cancer growth.

Several studies highlighted the importance of platelets in the tumor microenvironment due to their ability to interact with other cell types such as leukocytes, endothelial, stromal and cancer cells. Platelets can influence tumor development and metastasis formation through several processes consisting of the secretion of growth factors and cytokines and/or via direct interaction with cancer cells and endothelium. Patients with visceral obesity (VO) are susceptible to pro-thrombotic and pro-inflammatory states and to development of cancer, especially colon cancer. These findings provide us with the impetus to analyze the role of platelets isolated from VO patients in tumor growth and progression with the aim to explore a possible link between platelet activation, obesity and colon cancer. Here, using xenograft colon cancer models, we prove that platelets from patients with visceral obesity are able to strongly promote colon cancer growth. Then, sequencing platelet miRNome, we identify miR-19a as the highest expressed miRNA in obese subjects and prove that miR-19a is induced in colon cancer. Last, administration of miR-19a per se in the xenograft colon cancer model is able to promote colon cancer growth. We thus elect platelets with their specific miRNA abundance as important factors in the tumor promoting microenvironment of patients with visceral obesity.

Enterocyte superoxide dismutase 2 deletion drives obesity.

Compelling evidence support an involvement of oxidative stress and intestinal inflammation as early events in the predisposition and development of obesity and its related comorbidities. Here, we show that deficiency of the major mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD2) in the gastrointestinal tract drives spontaneous obesity. Intestinal epithelium-specific Sod2 ablation in mice induced adiposity and inflammation via phospholipase A2 (PLA2) activation and increased release of omega-6 polyunsaturated fatty acid arachidonic acid. Remarkably, this obese phenotype was rescued when fed an essential fatty acid-deficient diet, which abrogates de novo biosynthesis of arachidonic acid. Data from clinical samples revealed that the negative correlation between intestinal Sod2 mRNA levels and obesity features appears to be conserved between mice and humans. Collectively, our findings suggest a role of intestinal Sod2 levels, PLA2 activity, and arachidonic acid in obesity presenting new potential targets of therapeutic interest in the context of this metabolic disorder.

Adhesion of Platelets to Colon Cancer Cells Is Necessary to Promote Tumor Development in Xenograft, Genetic and Inflammation Models.

Platelets represent the linkage between tissue damage and inflammatory response with a putative role in tumorigenesis. Given the importance of the microenvironment in colon cancer development, we elucidated the eventual role of platelets-cancer cells crosstalk in in vivo colon cancermodels. To evaluate the involvement of platelets in intestinal tumorigenesis, we first analyzed if the ablation of ß-integrin P-selectin that drives platelets-cell adhesion, would contribute to platelets-colon cancer cell interaction and drive cancer progression. In a xenograft tumor model, we observed that when tumors are inoculated with platelets, the ablation of P-selectin significantly reduced tumor growth compared to control platelets. Furthermore, in genetic models, as well as in chronic colitis-associated colorectal carcinogenesis, P-selectin ablated mice displayed a significant reduction in tumor number and size compared to control mice. Taken together, our data highlights the importance of platelets in the tumor microenvironment for intestinal tumorigenesis. These results support the hypothesis that a strategy aimed to inhibit platelets adhesion to tumor cells are able to block tumor growth and could represent a novel therapeutic approach to colon cancer treatment.

Fibroblast Growth Factor 19 modulates intestinal microbiota and inflammation in presence of Farnesoid X Receptor.

BACKGROUND: Disruption of bile acid (BA) homeostasis plays a key role in intestinal inflammation. The gut-liver axis is the main site for the regulation of BA synthesis and BA pool size via the combined action of the nuclear Farnesoid X Receptor (FXR) and the enterokine Fibroblast Growth Factor 19 (FGF19). Increasing evidence have linked derangement of BA metabolism with dysbiosis and mucosal inflammation. Thus, here we aimed to investigate the potential action of an FGF19 analogue on intestinal microbiota and inflammation. METHODS: A novel engineered non-tumorigenic variant of the FGF19 protein, M52-WO 2016/0168219 was generated. WT and FXRnull mice were injected with AAV-FGF19-M52 or the control AAV-GFP and subjected to Sodium Dextran Sulphate-induced colitis. FINDINGS: FGF19-M52 reduced BA synthesis and pool size, modulated its composition and protected mice from intestinal inflammation. These events were coupled with preservation of the intestinal epithelial barrier integrity, inhibition of inflammatory immune response and modulation of microbiota composition. Interestingly, FGF19-M52-driven systemic and local anti-inflammatory activity was completely abolished in Farnesoid X Receptor (FXR)null mice, thus underscoring the need of FXR to guarantee enterocytes' fitness and complement FGF19 anti-inflammatory activity. To provide a translational perspective, we also show that circulating FGF19 levels are reduced in patients with Crohn's disease. INTERPRETATION: Reactivation of the FXR-FGF19 axis in a murine model of intestinal inflammation could bona fide provide positive changes in BA metabolism with consequent reduction of intestinal inflammation and modulation of microbiota. These results point to the therapeutic potential of FGF19 in the treatment of intestinal inflammation with concomitant derangement of BA homeostasis. FUNDING: A. Moschetta is funded by MIUR-PRIN 2017 <- 2017J3E2W2; Italian Association for Cancer Research (AIRC, IG 23239); Interreg V-A Greece-Italy 2014-2020-SILVER WELLBEING, MIS5003627; HDHL-INTIMIC EuJPI-FATMAL; MIUR PON "R&I" 2014-2020-ARS01_01220. No money has been paid by NGM Biopharmaceuticals or any other agency to write this article.

Hepatic microRNA Expression by PGC-1α and PGC-1ß in the Mouse.

The fine-tuning of liver metabolism is essential to maintain the whole-body homeostasis and to prevent the onset of diseases. The peroxisome proliferator-activated receptor-γ coactivators (PGC-1s) are transcriptional key players of liver metabolism, able to regulate mitochondrial function, gluconeogenesis and lipid metabolism. Their activity is accurately modulated by post-translational modifications. Here, we showed that specific PGC-1s expression can lead to the upregulation of different microRNAs widely implicated in liver physiology and diseases development and progression, thus offering a new layer of complexity in the control of hepatic metabolism.

PGC-1ß Induces Susceptibility To Acetaminophen-Driven Acute Liver Failure.

Acetaminophen (APAP) is a worldwide commonly used painkiller drug. However, high doses of APAP can lead to acute hepatic failure and, in some cases, death. Previous studies indicated that different factors, including life-style and metabolic diseases, could predispose to the risk of APAP-induced liver failure. However, the molecular process that could favor APAP hepatotoxicity remains understood. Here, we reported that a short-term high fat-enriched diet worsens APAP-induced liver damage, by promoting liver accumulation of lipids that induces the activation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC-1ß). Therefore, we challenged mice with hepatic-specific PGC-1ß overexpression on a chow diet with a subtoxic dose of APAP and we found that PGC-1ß overexpression renders the liver more sensitive to APAP damage, mainly due to intense oxidative stress, finally ending up with liver necrosis and mice death. Overall, our results indicated that during high fat feeding, PGC-1ß adversely influences the ability of the liver to overcome APAP toxicity by orchestrating different metabolic pathways that finally lead to fatal outcome.

PGC-1α induced browning promotes involution and inhibits lactation in mammary glands.

The PPARγ coactivator 1α (PGC-1α) is a transcriptional regulator of mitochondrial biogenesis and oxidative metabolism. Recent studies have highlighted a fundamental role of PGC-1α in promoting breast cancer progression and metastasis, but the physiological role of this coactivator in the development of mammary glands is still unknown. First, we show that PGC-1α is highly expressed during puberty and involution, but nearly disappeared in pregnancy and lactation. Then, taking advantage of a newly generated transgenic mouse model with a stable and specific overexpression of PGC-1α in mammary glands, we demonstrate that the re-expression of this coactivator during the lactation stage leads to a precocious regression of the mammary glands. Thus, we propose that PGC-1α action is non-essential during pregnancy and lactation, whereas it is indispensable during involution. The rapid preadipocyte-adipocyte transition, together with an increased rate of apoptosis promotes a premature mammary glands involution that cause lactation defects and pup growth retardation. Overall, we provide new insights in the comprehension of female reproductive cycles and lactation deficiency, thus opening new roads for mothers that cannot breastfeed.

Suppression of Hepatic Bile Acid Synthesis by a non-tumorigenic FGF19 analogue Protects Mice from Fibrosis and Hepatocarcinogenesis.

Critical regulation of bile acid (BA) pool size and composition occurs via an intensive molecular crosstalk between the liver and gut, orchestrated by the combined actions of the nuclear Farnesoid X receptor (FXR) and the enterokine fibroblast growth factor 19 (FGF19) with the final aim of reducing hepatic BA synthesis in a negative feedback fashion. Disruption of BA homeostasis with increased hepatic BA toxic levels leads to higher incidence of hepatocellular carcinoma (HCC). While native FGF19 has anti-cholestatic and anti-fibrotic activity in the liver, it retains peculiar pro-tumorigenic actions. Thus, novel analogues have been generated to avoid tumorigenic capacity and maintain BA metabolic action. Here, using BA related Abcb4-/- and Fxr-/- mouse models of spontaneous hepatic fibrosis and HCC, we explored the role of a novel engineered variant of FGF19 protein, called FGF19-M52, which fully retains BA regulatory activity but is devoid of the pro-tumoral activity. Expression of the BA synthesis rate-limiting enzyme Cyp7a1 is reduced in FGF19-M52-treated mice compared to the GFP-treated control group with consequent reduction of BA pool and hepatic concentration. Treatment with the non-tumorigenic FGF19-M52 strongly protects Abcb4-/- and Fxr-/- mice from spontaneous hepatic fibrosis, cellular proliferation and HCC formation in terms of tumor number and size, with significant reduction of biochemical parameters of liver damage and reduced expression of several genes driving the proliferative and inflammatory hepatic scenario. Our data bona fide suggest the therapeutic potential of targeting the FXR-FGF19 axis to reduce hepatic BA synthesis in the control of BA-associated risk of fibrosis and hepatocarcinoma development.

Deletion of Stearoyl-CoA Desaturase-1 From the Intestinal Epithelium Promotes Inflammation and Tumorigenesis, Reversed by Dietary Oleate.

BACKGROUND & AIMS: The enzyme stearoyl-coenzyme A desaturase 1 (SCD or SCD1) produces monounsaturated fatty acids by introducing double bonds into saturated bonds between carbons 9 and 10, with oleic acid as the main product. SCD1 is present in the intestinal epithelium, and fatty acids regulate cell proliferation, so we investigated the effects of SCD1-induced production of oleic acid in enterocytes in mice. METHODS: We generated mice with disruption of Scd1 selectively in the intestinal epithelium (iScd1-/- mice) on a C57BL/6 background; iScd1+/+ mice were used as controls. We also generated iScd1-/-ApcMin/+ mice and studied cancer susceptibility. Mice were fed a chow, oleic acid-deficient, or oleic acid-rich diet. Intestinal tissues were collected and analyzed by histology, reverse transcription quantitative polymerase chain reaction, immunohistochemistry, and mass spectrometry, and tumors were quantified and measured. RESULTS: Compared with control mice, the ileal mucosa of iScd1-/- mice had a lower proportion of palmitoleic (C16:1 n-7) and oleic acids (C18:1 n-9), with accumulation of stearic acid (C18:0); this resulted a reduction of the Δ9 desaturation ratio between monounsaturated (C16:1 n-7 and C18:1 n-9) and saturated (C16:0 and C18:0) fatty acids. Ileal tissues from iScd1-/- mice had increased expression of markers of inflammation activation and crypt proliferative genes compared with control mice. The iScd1-/-ApcMin/+ mice developed more and larger tumors than iScd1+/+ApcMin/+ mice. iScd1-/-ApcMin/+ mice fed the oleic acid-rich diet had reduced intestinal inflammation and significantly lower tumor burden compared with mice fed a chow diet. CONCLUSIONS: In studies of mice, we found intestinal SCD1 to be required for synthesis of oleate in the enterocytes and maintenance of fatty acid homeostasis. Dietary supplementation with oleic acid reduces intestinal inflammation and tumor development in mice.

Hepatic peroxisome proliferator-activated receptor γ coactivator 1ß drives mitochondrial and anabolic signatures that contribute to hepatocellular carcinoma progression in mice.

The peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1ß (PGC-1 ß) is a master regulator of mitochondrial biogenesis and oxidative metabolism as well as of antioxidant defense. Specifically, in the liver, PGC-1ß also promotes de novo lipogenesis, thus sustaining cellular anabolic processes. Given the relevant pathogenic role of mitochondrial and fatty acid metabolism in hepatocarcinoma (HCC), here we pointed to PGC-1ß as a putative novel transcriptional player in the development and progression of HCC. For this purpose, we generated both hepatic-specific PGC-1ß-overexpressing (LivPGC-1ß) and PGC-1ß knockout (LivPGC-1ßKO) mice, and we challenged them with both chemical and genetic models of hepatic carcinogenesis. Our results demonstrate a pivotal role of PGC-1ß in driving liver tumor development. Indeed, whereas mice overexpressing PGC-1ß show greater tumor susceptibility, PGC-1ß knockout mice are protected from carcinogenesis. High levels of PGC-1ß are able to boost reactive oxygen species (ROS) scavenger expression, therefore limiting the detrimental ROS accumulation and, consequently, apoptosis. Moreover, it supports tumor anabolism, enhancing the expression of genes involved in fatty acid and triglyceride synthesis. Accordingly, the specific hepatic ablation of PGC-1ß promotes the accumulation of ROS-driven macromolecule damage, finally limiting tumor growth. CONCLUSION: The present data elect hepatic PGC-1ß as a transcriptional gatekeeper of mitochondrial function and redox status in HCC, orchestrating different metabolic programs that allow tumor progression. (Hepatology 2018;67:884-898).

Long-term Administration of Nuclear Bile Acid Receptor FXR Agonist Prevents Spontaneous Hepatocarcinogenesis in Abcb4-/- Mice.

Altered bile acid (BA) signaling is associated with hepatotoxicity. The farnesoid X receptor (FXR) is a nuclear receptor that transcriptionally regulates BA homeostasis. Mice with FXR ablation present hepatocarcinoma (HCC) due to high toxic BA levels. Mice with Abcb4 ablation accumulate toxic BA within the bile ducts and present HCC. We have previously shown that intestinal specific activation of FXR by transgenic VP16-FXR chimera is able to reduce BA pool size and prevent HCC. Here we tested chemical FXR activation by administering for 15 months the dual FXR/ membrane G protein-coupled receptor (TGR5) agonist INT-767 (6α-ethyl-3α,7α,23-trihydroxy-24-nor-5ß-cholan-23-sulphate) to Fxr-/- and Abcb4-/- mice. HCC number and size were significantly reduced by INT-767 administration. In contrast, no changes in HCC tumor number and size were observed in Fxr-/- mice fed with or without INT-767. Notably, INT-767 preserved the hepatic parenchyma, improved hepatic function and down-regulated pro-inflammatory cytokines. Moreover, in Abcb4-/- mice INT-767 prevented fibrosis by reducing collagen expression and deposition. Thus, long term activation of FXR is able to reduce BA pool, reprogram BA metabolism and prevent HCC. These data provide the impetus to address the bona fide therapeutic potential of FXR activation in disease with BA-associated development of HCC.

Biliary Phospholipids Sustain Enterocyte Proliferation and Intestinal Tumor Progression via Nuclear Receptor Lrh1 in mice.

The proliferative-crypt compartment of the intestinal epithelium is enriched in phospholipids and accumulation of phospholipids has been described in colorectal tumors. Here we hypothesize that biliary phospholipid flow could directly contribute to the proliferative power of normal and dysplastic enterocytes. We used Abcb4-/- mice which lack biliary phospholipid secretion. We first show that Abcb4-/- mice are protected against intestinal tumorigenesis. At the molecular level, the transcriptional activity of the nuclear receptor Liver Receptor Homolog-1 (Lrh1) is reduced in Abcb4-/- mice and its re-activation re-establishes a tumor burden comparable to control mice. Feeding Abcb4-/- mice a diet supplemented with phospholipids completely overcomes the intestinal tumor protective phenotype, thus corroborating the hypothesis that the absence of biliary phospholipids and not lack of Abcb4 gene per se is responsible for the protection. In turn, phospholipids cannot re-establish intestinal tumorigenesis in Abcb4-/- mice crossed with mice with intestinal specific ablation of Lrh1, a nuclear hormone receptor that is activates by phospholipids. Our data identify the key role of biliary phospholipids in sustaining intestinal mucosa proliferation and tumor progression through the activation of nuclear receptor Lrh1.

Avaliação dos resultados obtidos através dos tratamentos fisioterápicos convencional e isostretching em 60 pacientes com síndrome do impacto na articulação do ombro / Evaluation of results obtained through conventional physiotherapy and isostretching treatments in 60 patients with impingement syndrome in the shoulder joint

A Síndrome do Impacto (SI) e a doença ocupacional possuem necessidades de diagnóstico e de tratamento onde a reabilitação possui papel importante no controle da dor e no retorno às atividades laborais e de recreação. No presente estudo buscaram-se investigar quais foram às alterações existentes em indivíduos que apresentavam SI: qual o domínio da Qualidade de Vida (QV) estava alterado, qual a incapacidade, os sintomas e a Amplitude de Movimento (ADM) dos membros superiores (MMSS) e quais as diferenças entre os tratamentos fisioterápicos convencional e "Isostreching". Após as análises estatísticas, verificou-se que 50% dos voluntários estudados eram do gênero masculino nos dois grupos e que o ombro dominante era o direito. A SI foi referida bilateralmente em 56,67% dos indivíduos do Grupo I e em 46,66% do Grupo II somente no ombro direito. Quanto à aderência aos tratamentos foi alta nos 2 grupos. Após os tratamentos, os resultados mostraram que em relação aos 8 domínios da QV, obteve-se melhora na Capacidade funcional, Vitalidade, Aspectos Sociais e Saúde Mental, sendo o Grupo I apresentou melhores resultados. Quanto aos domínios: Estado Geral de Saúde e Aspecto Emocional obteve-se pouca melhora nos dois grupos. A melhora do domínio Dor destacou-se no Grupo I em relação ao tratamento convencional do Grupo II. O Questionário de Incapacidade do Braço, Ombro e Mão (DASH), auxiliou na análise dos resultados dos sintomas e da incapacidade nos indivíduos com SI. As respostas deste questionário mostraram que os sintomas e a incapacidade obtiveram melhores resultados com o Grupo I em relação ao Grupo II. Quanto à Goniometria, não houve diferença estatística no ganho da ADM entre os 2 grupos, mas houve ganho percentual importante com os dois tratamentos, onde o ombro direito obteve ganho maior do que o lado esquerdo mesmo com a bilateralidade do lado acometido sendo alta no Grupo I.

Impact Syndrome (IS) and occupational diseases have diagnosis and treatment needs where rehabilitation has an important role for pain management and return to work and to normal physical activities. With this study sought to identify changes in people suffering IS: what domain of Quality of Life (QOL) was altered, which disabilities, symptoms and Range of Motion (ROM) of the upper limbs and, also, the differences between conventional physiotherapy and "Isostreching". After statistical analysis, it was found that 50% of subjects studied were male in both groups and the dominant shoulder was right. The IS was reported bilaterally in 56.67% of patients in Group I and and only on the right shoulder in 46.66% of cases in Group II. Adherence to treatment was high in two groups. After treatments, the results showed that in relation to the 8 domains of QOL, obtained an improvement in Functional Capacity, Vitality, Social Functioning, and Mental Health, with best results in Group I. For the domains: General Health and Emotional Aspect obtained little improvement in both groups. The improved in the domain Pain stood out in Group I compared to Group II with conventional treatment. The Questionnaire Disability of the Arm, Shoulder and Hand (DASH), supported the analysis of the results of symptoms and disability in individuals with IS. The answers to this questionnaire indicated that symptoms and disability fared better in Group I than in Group II. As for goniometry, there was no statistical difference in the gain of ROM comparing the groups, but there were important percentage gain with both treatments, which had earned the right shoulder higher than the left one, even with the bilaterality of the affected side being high in Group I.

Melhora na qualidade de vida e da dor referida em trabalhadores com síndrome do impacto após aplicação do método Isostretching / Improvement in the quality of life and pain intensity among workers with shoulder impingement syndrome after application of the Isostretching method

Introdução: Entre os Distúrbios Osteomusculares Relacionadas ao Trabalho (DORT), a Síndrome do Impacto do ombro (SI) é a principal causa de incapacidade para o trabalho. Além do afastamento do trabalho, muitos casos necessitam de tratamento fisioterapêutico. O método Isostretching pode ser uma das alternativas e pode contribuir para a melhora da qualidade de vida dos trabalhadores com SI. Objetivo: Verificar os efeitos da aplicação de um protocolo de tratamento baseado no método Isostretching, em indivíduos portadores de SI, na melhora da qualidade de vida e intensidade da dor. Método: Mediante a analise de prontuários de pacientes, em tratamento no ambulatório de medicina do trabalho e outros ambulatórios da Unicamp, foram selecionados 30 voluntários, submetidos á aplicação de 12 sessões de fisioterapia com o método Isostretching, durante 6 semanas. Os voluntários foram avaliados antes e após o protocolo proposto através do questionário de qualidade de vida SF-36 e escala visual numérica de dor. Os dados foram analisados mediante uma análise de variâncias (ANOVA), o qual foi realizado através do software R, versão 2.12.0. Resultados: Os obtidos no questionário de qualidade de vida SF-36 mostraram diferenças estatisticamente significantes (p<0,05) para a maioria dos domínios. Na escala visual numérica, de zero a dez, o valor médio foi de 6,63 pré-tratamento e, no pós-tratamento foi de 3,23 pontos, foi significativo (p<0,05). Conclusão: O protocolo proposto foi eficaz na melhora da qualidade de vida e na diminuição do quadro álgico do grupo de voluntários estudado.

Introduction: Among Work-Related Musculoskeletal Disorders, the Shoulder Impingement Syndrome (SIS) is the leading cause of work disability. Aside being off work, many cases often require physiotherapy. The Isostretching method can be an alternative and can contribute to improving the quality of life of workers with SIS. Objective: To verify the effects of a treatment protocol based on the Isostretching method in individuals with SIS, in improving the quality of life and decreasing pain intensity. Method: By analyzing patient records in treatment at the occupational health clinic and other Unicamp clinics, 30 volunteers were selected and submitted to 12 physiotherapy sessions with the Isostretching method for 6 weeks. The volunteers were evaluated before and after the proposed protocol using the SF-36 quality of life questionnaire and a visual numeric pain scale. Data was analyzed using (ANOVA) variance analysis, which was performed using software R, version 2.12.0. Results: The results of the SF-36 quality of life questionnaire showed statistically significant differences (p <0.05) in most areas. In the visual numeric scale from zero to ten, the average value was 6.63 points pre-treatment and 3.23 post-treatment, which was significant (p <0.05). Conclusion: The proposed protocol was effective in improving the quality of life and in reducing pain in the group of volunteers studied.

Avaliação da qualidade de vida e dos sintomas de stress em mulheres menopausadas com disfunção da articulação temporomandibular / Quality of life and stress symptoms evaluation in post menopausal women with temporomandibular joint disorders

A literatura tem relatado que mulheres com sintomas de disfunção temporomandibular (DTM) podem apresentar depressão, ansiedade e stress pela constância da sintomatologia de desconforto e dor. O objetivo geral foi: avaliar a qualidade de vida (QV) e os sintomas de stress em mulheres menopausadas com DTM que freqüentavam o serviço do Centro de Saúde da Comunidade (CECOM)/ Coordenadoria de Serviços Sociais (CSS) da Universidade Estadual de Campinas (UNICAMP) e os objetivos específicos foram: verificar se apresentavam ou não stress, qual a fase de stress, quais os sintomas de stress e como e quanto a QV delas foi alterada. Selecionamos 30 mulheres voluntárias da UNICAMP, com idades entre 38 e 65 anos, diagnosticadas como portadoras da sintomatologia de DTM e com menopausa clinicamente comprovada. Foram avaliadas através de uma ficha de anamnese, do Questionário de Qualidade de Vida SF-36 (QQV SF-36) e do Inventário de Sintomas de Stress de Lipp (ISSL). Os resultados mostraram que as mulheres apresentaram dor crônica, sendo 73% das dores nos músculos masseter e escaleno, 63% dor nas Articulações Temporomandibulares (ATMs), 56% nas ATMs e nos músculos pterigóideo lateral e pterigóideo medial, 50% no ângulo da mandíbula e 46% no músculo rombóide. Quanto à QV os piores escores foram relacionados com aspectos físicos, dor e vitalidade. A fase de stress com maior escore, 46,67%, foi a fase de resistência e os sintomas de stress com maior porcentagem foram os psicológicos com 43,33%.

The literature has reported that women with symptoms of temporomandibular joint disorders (TMJ) may have depression, anxiety and stress due to constancy of symptoms of discomfort and pain. The aim of this study was to evaluate quality of life and stress symptoms in post menopausal women with TMJ who attended the Community Health Center/Social Service Coordination of State University of Campinas (UNICAMP) and the main objectives are: to verify if they were under stress or not, in which stage, which were the symptoms and how their quality of life has changed. 30 voluntary women of UNICAMP, 38 to 65 years old, diagnosed with TMJ and menopause clinically supported, were selected. They were evaluated through an anamnesis form, a Quality of Life Questionnaire SF-36 (QLQ SF-36) and the Lipp Stress Symptoms Inventory (LSSI). The results showed that women had chronic pain, 73% masseter and scalenus muscle pain, 63% temporomandibular joints (TMJ) pain, 56% in TMJ and the lateral and medial pterygoid muscles, 50% mandibular angle and 46% rhomboid muscle. Regarding quality of life the worst scores were related to physical aspects, pain and vitality. The stress stage with higher score, 46.67%, was the resistance phase and the stress symptoms with higher percentage were the psychological with 43.33%.