Search

Background: Pandemic of COVID-19, the potentially fatal disease caused by SARS-CoV-2, had caused intangible consequences on global health systems, economy, daily life, education, travel, leisure, work, and mental health. Its impact on mental and physical health, especially in health professionals, has been described. Objective: This study aimed to review and discuss the published evidence regarding the presence of headache on COVID-19 healthcare workers. Methods: In this review, we searched for all articles published in various data bases including PubMed / Medline, Scopus, and Web of Science and all original research studies, letters to editor, case reports, commentaries and reviews published in English, Portuguese or Spanish were searched. Two researchers independently analyzed published articles in order to include/exclude based on inclusion or exclusion criteria. Results: Thirteen articles were included. All studies included in this review were observational; eleven were cross-sectional studies, one was a prospective/cohort and one was a retrospective. Two studies evaluated psychological outcomes, mental health disorders and associated factors, one study investigated symptoms and causes of somatic symptom disorder and all other studies evaluated headaches associated with Personal Protective Equipment (PPI). Conclusions: The present review shows that COVID-19 pandemic has negative impact on physical and mental health in healthcare workers and headache has been associated to psychological stress and work overload during pandemic. Further studies are necessary to better investigate COVID-19 pandemic effects on headaches and other neurological conditions.

Fridericia chica (Bonpl.) L.G. Lohmann, Bignoniaceae, is an Amazonian species known as “pariri” or “crajiru” that is included in the Brazilian National List of Medicinal Plants of Interest to the Unified Health System (Renisus). This herbal remedy is traditionally used as an infusion to treat diarrhea, anemia, inflammation, symptoms of mucositis, and frequent complications of chemotherapy. This study aimed to characterize the chemical profile of the hydroethanolic extract of F. chica and to assess its intestinal anti-inflammatory activity. The chemical profile of the leaves was determined by ultra-performance liquid chromatography coupled to mass spectrometry, and its potential anti-inflammatory activity in the gut was evaluated in mucositis induced by 5-fluorouracil. Three novel compounds from this the species were identified 6,7,3′,4′-tetrahydroxy-5-methoxyflavilium-O-glucuronide, scutellarein-O-glucuronide, and 5-methyl-scutellarein-O-glucuronide, as well as flavones and anthocyanidins that have been previously described. Mice received the hydroethanolic extract (300 mg/kg) for 9 days, and no signs of toxicity were observed. After 72 h of 5-fluorouracil administration, intestinal permeability, bacterial translocation, myeloperoxidase activity, eosinophil peroxidase activity, and histological analyses were performed. Treatment with the analyzed extract was beneficial, as it normalized intestinal permeability, bacterial translocation, myeloperoxidase activity/eosinophil peroxidase and preserved intestinal epithelium architecture. This study provides new insights into the chemical composition and biological activity of the polar extracts from “pariri”, an important Amazonian crude medicinal drug.

Purpose To identify and synthesize evidence on strategies used to train chewing and swallowing in individuals with temporomandibular disorder and orofacial pain. Research strategy Scoping review conducted by search in MEDLINE, LILACS, BBO, IBECS, BINACIS, CUMED, SOF, DeCS, Index Psi, LIPECS, and ColecionaSUS (via VHL), Scopus, CINAHL, Embase, Web of Science, Cochrane, and the grey literature: Brazilian Digital Theses and Dissertations Library (BDTD), OpenGrey, and Google Scholar. Selection criteria Quantitative or qualitative studies, with no restriction on time or language of publication, with the following descriptors or keywords: Temporomandibular Joint; Temporomandibular Joint Dysfunction Syndrome; Temporomandibular Joint Disorders; Facial Pain; chewing (Mastication); swallowing (Deglutition); Therapeutics; Myofunctional Therapy; Speech, Language and Hearing Sciences. In the first stage, two reviewers independently screened the studies by title and abstract reading. In the second stage, the reviewers independently read the preselected documents in full text. In case of divergences, a third researcher was consulted. Results The 11 documents included in the review were published between 2000 and 2018. The mostly used training strategies were simultaneous bilateral mastication/chewing, followed by alternating bilateral mastication. In swallowing, increased mastication time was proposed to break food into smaller bits and better lubricate the bolus; training with upper tongue support was also indicated. Conclusion Functional training proved to be effective in rehabilitation, although it was not standardized or performed alone. The studies had low levels of evidence. It is essential to conduct more encompassing and standardized studies, such as randomized clinical trials.

Dentists are exposed to contamination by SARS-CoV-2 due to dental interventions, leading to a state of alert and potential risk of negative impact in mental health and sleep quality, associated with Temporomandibular Disorder (TMD) and bruxism. Objective: to evaluate the psychosocial status, sleep quality, symptoms of TMD, and bruxism in Brazilian dentists (DSs) during the COVID-19 pandemic. Methodology: The sample (n=641 DSs) was divided into three groups (quarantined DSs; DSs in outpatient care; and frontline professionals), which answered an electronic form containing the TMD Pain Screening Questionnaire (Diagnostic Criteria for Temporomandibular Disorders – DC/TMD), the Pittsburgh Sleep Quality Index (PSQI), the Depression, Anxiety and Stress Scale (DASS-21), and the sleep and awake bruxism questionnaire. ANOVA test and Mann Whitney post-test were used, with Bonferroni adjustment (p

C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) develop neurological symptoms and die 6--7-day post-inoculation in the absence of high parasitemia. The effects of chronic intake of a high-fat diet on this process are largely unknown. In this study, we assessed the effect of a high-fat diet on the host-parasite response to malarial infection. Mice were fed ad libitum with either standard or a high-fat diet for 8 weeks and afterwards were infected with PbA. PbA-infected mice feeding a standard diet presented blood parasitemia, hepatic and cerebral histopathological alterations, and hepatic injury with increased hemozoin deposition in the liver. By contrast, these changes were not observed in the malaria high-fat diet group. In addition, mice fed a high-fat diet did not develop the expected neurological symptoms of cerebral malaria and were resistant to death. Taken together, our results indicate that chronic ingestion of high-fat diet prevents the development of experimental malaria induced by PbA injection, suggesting a relationship between a high-fat diet and malaria, which is an interesting subject for further study in humans.

This study evaluated the mechanisms action of arginine in experimental model of ulcerative colitis. C57BL/6 mice were randomized into 4 groups: Control group (C): standard diet; Colitis group (Col): standard diet and DSS solution; Pretreated group (PT): diet supplementation with arginine before and during colitis induction; Treated group (T): diet supplementation with arginine during colitis induction. Colitis was induced by administration of 1.5% DSS for 5 days. Parameters such as intestinal permeability (IP), bacterial translocation (BT), histological and morphometric analysis, cytokines, immunoglobulin A, inflammatory infiltrate, oxidative stress, tight junction, iNOS1 Nitric oxide indutase.1 were performed. The Col group showed increased IP, BT, oxidative stress and inflammatory infiltrate in the colon. Arginine decreased IP, BT, oxidative stress and inflammatory infiltrate in the colon. Only, the group T reduced iNOS, cytokine IL-17,2 Interleukine 17.2 and increased collagen area and cytokine TGF-β.3 Transforming growth factor beta.3 These results suggest that arginine can constitute in potential therapy for colitis.

Pain is one of the most common and troublesome non-motor symptoms of Parkinson’s disease (PD). The King's Parkinson's Disease Pain Scale (KPPS) is the first scale of its kind to evaluate the burden and characterization of various phenotypes of pain in individuals with PD. The purpose of this study was to adapt the KPPS to Brazilian culture and to assess its content validity using the Delphi method. The process of adapting the original instrument to the Brazilian context occurred in six stages according to international standards. Following the pilot tests with individuals with PD, the pre-final version of the KPPS-Brazil was developed and submitted to judges to assess content validity. Three evaluation rounds were conducted, in which several corrections and changes suggested by the judges were accepted. The Content Validity Index (CVI) was calculated to determine the judges’ degree of agreement. The results demonstrated that the KPPS-Brazil showed a quite satisfactory level of semantic, idiomatic, cultural, and conceptual equivalence. The judges' opinion showed adequate content validity for all of the KPPS-Brazil items and the scale. The use of the KPPS-Brazil will enable an adequate assessment of pain in individuals with PD, contributing to clinical practice and research.

BACKGROUND AND OBJECTIVES: Botulinum neurotoxin type A has been an interesting therapeutic complement to the conventional treatment of trigeminal neuralgia, especially in patients without satisfactory response to pharmacotherapy and/or surgical procedures. A detailed and comprehensive literature review its important for the description of the available evidence, allowing for a critical view on the topic. Therefore, this study's objective was to describe the scientific evidence on the use of botulinum toxin type A in the trigeminal neuralgia treatment. CONTENTS: Pubmed and Scielo databases were searched using the descriptors: "trigeminal neuralgia and botulinum toxin". Inclusion criteria were human studies (open-label, double-blind, randomized, and placebo-controlled trials) and reviews of the use of botulinum toxin type A in trigeminal neuralgia treatment, published in English, Spanish or Portuguese from January 2008 to March 2020. Twenty-one articles met the inclusion criteria. Overall, studies demonstrated that botulinum toxin type A significantly reduced pain intensity and paroxysmal episodes, as well as improved quality of life. CONCLUSION: Use of botulinum toxin type A in treatment of refractory trigeminal neuralgia shows promising results, but further studies are needed to increase the knowledge and consolidation of this therapeutic alternative. RESUMO JUSTIFICATIVA E OBJETIVOS: A neurotoxina botulínica do tipo A tem se mostrado interessante como opção terapêutica complementar ao tratamento convencional da neuralgia trigeminal, sobretudo em pacientes sem resposta satisfatória à farmacoterapia e/ou procedimentos cirúrgicos. Uma revisão da literatura detalhada e abrangente se faz importante para descrever as evidências disponíveis e permitir uma visão crítica sobre o tema. Sendo assim, este estudo teve como objetivo apresentar as evidências científicas disponíveis na literatura sobre o uso da neurotoxina botulínica do tipo A no tratamento da neuralgia trigeminal. CONTEÚDO: Foi realizada uma busca nas bases de dados Pubmed e Scielo utilizando-se os seguintes descritores "trigeminal neuralgia and botulinum toxin". Os critérios de inclusão foram estudos em humanos (estudos abertos e ensaios clínicos duplamente encobertos, randomizados e controlados por placebo) e revisões sobre o uso da neurotoxina botulínica do tipo A no tratamento da neuralgia trigeminal nos idiomas inglês, espanhol ou português durante o período de janeiro de 2008 a março de 2020. Apenas 21 artigos preencheram os critérios de inclusão. De um modo geral, os trabalhos demonstraram efeitos significativos da neurotoxina botulínica do tipo A na diminuição da intensidade da dor e no número de episódios paroxísticos, assim como na melhoria da qualidade de vida. CONCLUSÃO: O uso da neurotoxina botulínica do tipo A no tratamento da neuralgia trigeminal refratária apresenta resultados promissores, mas são necessários novos estudos para ampliação do conhecimento e consolidação dessa alternativa terapêutica.

BACKGROUND AND OBJECTIVES Use of Integrative and Complementary Health Practices (ICHP) in pain management has increased, mainly due to the biopsychosocial nature of pain. The objective of this work is to evaluate the knowledge and use of ICHP in patients with orofacial pain and describe the sociodemographic profile of patients that use these therapies. METHODS This is a cross-sectional study and data collection was performed through a questionnaire about knowledge, use and interest in ICHP in a sample of patients with orofacial pain. Adult patients of both sexes under treatment from August 2018 to July 2019 at orofacial pain specialized services were included. RESULTS Fifty-six patients (84.8%) were female and among those 97% had previous knowledge of complementary practices, with acupuncture being the most known (89.6%). In addition, 59% of participants used therapies for orofacial pain, mainly phytotherapy (28.8%). Ninety-seven percent showed interest in knowledge and use of complementary therapies. Among users, the majority was female. CONCLUSION The patients know and use ICHP to relieve orofacial pain and show great interest in the field which justifies inclusion of complementary practices for management of orofacial pain. RESUMO JUSTIFICATIVA E OBJETIVOS A utilização de Práticas Integrativas e Complementares em Saúde (PICS) no tratamento da dor tem aumentado, sobretudo em função da natureza biopsicossocial da dor. O objetivo foi avaliar o conhecimento e uso das PICS em pacientes com dor orofacial e conhecer o perfil sociodemográfico dos pacientes que utilizam essas terapias. MÉTODOS Estudo do tipo transversal, com pacientes atendidos de agosto de 2018 a julho de 2019 nas clínicas de dor orofacial. A coleta de dados foi feita por meio de um questionário sobre conhecimento, uso e interesse a respeito das PICS. RESULTADOS Dos 66 pacientes, 56 (84,8%) eram mulheres. Desses, 97% conheciam as práticas integrativas, sendo a acupuntura a mais conhecida (89,6%). Ademais, 59% dos participantes fizeram uso de alguma terapia para dor orofacial, sendo a fitoterapia a mais utilizada (28,8%), e 97% tinham interesse em conhecer e utilizar as práticas. CONCLUSÃO Pacientes com dor orofacial conhecem e utilizam as PICS para alívio da dor e promoção do bem-estar. Há grande interesse pelas práticas, fato que estimula a inclusão no tratamento complementar da dor orofacial.

Background Masticatory myofascial pain is the most prevalent muscular temporomandibular disorder (TMD). It primarily affects masseter and temporal muscles. Several treatments, including acupuncture, have been recommended. However, systematic reviews have highlighted gaps in studies and absence of conclusive results. Objectives We performed a randomized controlled clinical trial to evaluate the effectiveness of acupuncture in improving pain, mandibular function, and oral health-related quality of life in women with masticatory myofascial pain. Methods Thirty-six patients diagnosed with masticatory myofascial pain according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were divided into the following two groups: acupuncture or control (non-penetrating acupuncture).Treatment was performed weekly for 5 weeks, and pain, mandibular function, and oral health-related quality of life were evaluated one week before treatment, one week after treatment, and one month after treatment. Non-parametric and parametric tests were used for comparisons between times and treatment groups (significance level of p≤0.05). Results The acupuncture group showed a significant reduction in pain (p≤0.01), which was not observed in the control group. Pain intensity was reduced by 61% and 84% at 1 week and 1 month after treatment, respectively. Both groups showed significant improvements in mandibular function and oral health-related quality of life over time (p≤0.01). Statistical analysis did not show a significant difference between the groups for any other evaluated outcome (p>0.05). Conclusion Although acupuncture was effective in pain reduction, nonspecific factors may have influenced mandibular function and oral health-related quality of life improvements in both groups, and this needs to be further addressed.

ObjectiveTrigeminal neuralgia is defined as a sudden severe shock-like pain within the distribution of the trigeminal nerve. Pain is a subjective experience that is influenced by gender, culture, environment, psychological traits, and genes. Sodium channels and nerve growth factor play important roles in the transmission of nociceptive signals and pain. The aim of this study was to investigate the occurrence of Nav1.7 sodium channel and nerve growth factor receptor TrkA gene polymorphisms (SCN9A/rs6746030 and NTRK1/rs633, respectively) in trigeminal neuralgia patients.MethodsNinety-six subjects from pain specialty centers in the southeastern region of Brazil were divided into 2 groups: 48 with classical trigeminal neuralgia diagnosis and 48 controls. Pain was evaluated using the visual analog scale and multidimensional McGill Pain Questionnaire. Genomic DNA was obtained from oral swabs in all individuals and was analyzed by real-time polymerase chain reaction.ResultsNo association was observed between evaluated polymorphisms and trigeminal neuralgia. For allele analyses, patients and controls had similar frequencies for both genes. Genotype distribution or allele frequencies of polymorphisms analyzed here did not correlate to pain scores.ConclusionsAlthough no association of evaluated polymorphisms and trigeminal neuralgia diagnosis or pain severity was observed, our data do not exclude the possibility that other genotypes affecting the expression of Nav1.7 or TrkA are associated with the disease. Further studies should investigate distinct genetic polymorphisms and epigenetic factors that may be important in expression of these molecules.

Mucositis is a side effect observed in patients undergoing chemotherapy. Besides, this treatment also leads to the imbalance of the intestinal microbiota. This study evaluated the effects of pre and treatment with fructo-oligosaccharides (FOS) in intestinal mucositis induced by 5-fluorouracil (5-FU). Balb/c mice were divided into four groups: CTL (without mucositis + saline), MUC (mucositis + saline), PT (mucositis + 6% FOS before disease induction) and T (mucositis + 6% FOS after disease induction). Mucositis was induced with an intraperitoneal injection of 300 mg/kg 5-FU. After 72 h intestinal permeability (IP), inflammatory infiltrate, oxidative stress, histological analysis, and short-chain fatty acids (SCFA) production were evaluated. The MUC group showed lost weight, intense inflammatory infiltrate, increased oxidative stress and IP (P

Objective To describe the morphological characteristics and asymmetries between the left and right mandibular condyles in Brazilian cadaveric specimens. Material and Methods Thirty-two jaws were placed on a rigid support for image acquisition of the frontal and lateral views. The shapes of the mandibular condyles were classified, and measurements of the distance between the anatomical landmarks in the lateral and frontal views were performed. Results Mandibular length and width were not different between the right and left sides. Regarding the shapes of the mandibular condyles, the rounded type was the most frequent, followed by marked medial slope; flattened; overhanging lateral and medial slopes; downward flattening of both slopes and their merger in a single, extensive surface; and deformity and marked lateral slope with flaring and flattening. Asymmetry between the left and right mandibular condyles was present in 40% of the specimens. Conclusion The anatomy of mandibular condyles varies greatly, and this knowledge can avoid misdiagnosis by image examination of the anatomic variations.

Viscosupplementation is a minimally invasive technique that replaces synovial fluid by intra-articular injection of hyaluronic acid (HA). Although effective in some joints, there is not conclusive evidence regarding temporomandibular disorders. This case series described the efficacy of a viscosupplementation protocol in intra-articular temporomandibular disorders. Ten patients with a diagnosis of disc displacement and/or osteoarthritis by Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were submitted to four monthly injections of low or medium molecular weight HA. Pain, mandibular function, image analysis by tomography and magnetic resonance, and quality of life were assessed at baseline and follow-ups (1 and 6 months). Pain, jaw range-of-motion, mandibular function, and quality of life improved at follow-up evaluations. Osteoarthritis changes decreased, and 20% of patients improved mandibular head excursion after treatment. Resolution of effusion and improvement in disc morphology were observed for most patients. This viscosupplementation protocol reduced pain and symptoms associated with internal derangement of temporomandibular joint, improved quality of life, and showed benefits from both low and medium molecular weight HA in alternate cycles.

Subjects Trigeminal neuralgia is a neuropathic pain characterized by episodes of severe shock-like pain within the distribution of one or more divisions of the trigeminal nerve. Pain can be influenced by ethnicity, environment, gender, psychological traits, and genetics. Molecules Nav1.6 sodium channel, Brain-derived Neurotrophic Factor, Catechol-O-methyltransferase and Guanosine Triphosphate Cyclohydrolase 1 have been involved in mechanisms that underlie pain and neurological conditions. Objective The aim of this case-control study was to investigate the occurrence of genetic polymorphisms in Nav1.6 sodium channel (SCN8A/rs303810), Brain-derived Neurotrophic Factor (BDNF/rs6265/Val66Met), Catechol-O-methyltransferase (COMT/rs4680/Val158Met), and Guanosine Triphosphate Cyclohydrolase 1 (GCH1/rs8007267) genes in trigeminal neuralgia patients. Methods Ninety-six subjects were divided into two groups: 48 with trigeminal neuralgia diagnosis and 48 controls. Pain was evaluated by visual analog scale and genomic DNA was obtained from oral swabs and analyzed by real-time polymerase chain reaction. Results No association was observed among SCN8A, BDNF, COMT or GCH1 polymorphisms and the presence of trigeminal neuralgia. Genotype distribution and allele frequencies did not correlate to pain severity. Conclusions Although no association of evaluated polymorphisms and trigeminal neuralgia or pain was observed, our data contributes to the knowledge of genetic susceptibility to trigeminal neuralgia, which is very scarce. Further studies may focus on other polymorphisms and mutations, as well as on epigenetics and transcriptional regulation of these genes, in order to clarify or definitively exclude the role of Nav1.6, BDNF, COMT or GCH1 in trigeminal neuralgia susceptibility and pathophysiology.

Introduction: Temporomandibular disorders (TMD) are a group of conditions that cause pain and dysfunction in the joint and muscles that control jaw movement. The etiology of TMD is multifactorial and multidisciplinary approaches are important for differential diagnosis and treatment planning [1–3]. This case report describes a viscosupplementation protocol with 4 cycles of sodium hyaluronate with different molecular weights to control osteoarthritis, disk displacement with reduction and intermittent closed lock of a 47-year-old woman with a 10-year history of temporomandibular pain and impaired function. Materials and methods: Careful anamnesis and detailed clinical examination showed several signs and symptoms, such as facial pain, joint click and discomfort in chewing. Diagnosis consisted of disk displacement with reduction and synovitis. Osteoarthritis of temporomandibular joint (TMJ) and bone structures was confirmed by computed tomography (CT).Treatment was performed in a multidisciplinary group involving experts in orofacial pain, physiotherapist and psychologist. Four monthly intra-articular injections of sodium hyaluronate (Polireumin®: molecular weight 500–730 kDa and Osteonil®: molecular weight 1.000–2.000 kDa) were applied in both temporomandibular joints followed by physical therapy during 4 consecutive months. Protocol consisted of Polireumin® injection in first and third applications and Osteonil® in second and forth months. Results: At end of treatment, patient showed great improvement in internal articular derangement and full restoration of function by clinical examination , control of all joint and bone changes by CT, and complete abolition of pain. After a 3- years follow-up, patient remained without pain or dysfunction in TMJ biomechanics and the osteoarthritis was under control. Discussion and conclusions: This case report demonstrates a successful protocol of viscosupplementation with an excellent control of TMD signs and symptoms. Further studies are necessary to assess the results of this protocol under a controlled clinical trial model.

Gastrointestinal mucositis is a major problem associated with cancer therapy. To minimize these deleterious effects, simultaneous administration of antioxidant components, such as selenium, can be considered. There is a growing interest in the use of yeasts because they are able to convert inorganic selenium into selenomethionine. In the present study, oral administration of Saccharomyces cerevisiae UFMG A-905 enriched with selenium was evaluated as an alternative in minimizing the side effects of 5FU-induced mucositis in mice. Mice body weight, food consumption, faeces consistency and the presence of blood in faeces were assessed daily during experimental mucositis induced by 5-fluorouracil (5FU). Blood was used for intestinal permeability determination, and small intestine for oxidative stress, immunological and histopathological examination. The increased intestinal permeability observed with mucositis induction was partially reverted by S. cerevisiae and selenium-enriched yeast. Both treatments were able to reduce myeloperoxidase activity, but only selenium-enriched yeast reduced eosinophil peroxidase activity. CXCL1/KC levels, histopathological tissue damage and oxidative stress (lipid peroxidation and nitrite production) in the small intestine were reduced by both treatments; however, this reduction was always higher when treatment with selenium-enriched yeast was evaluated. Results of the present study showed that the oral administration of S. cerevisiae UFMG A-905 protected mice against mucositis induced by 5-FU, and that this effect was potentiated when the yeast was enriched with selenium.

The etiology of trigeminal neuropathic pain is not clear, but there is evidence that demyelination, expression of cytokines, neuropeptides, and neurotrophic factors are crucial contributors. In order to elucidate mechanisms underlying trigeminal neuropathic pain, we evaluated the time course of morphological changes in myelinated and unmyelinated trigeminal nerve fibers, expression of cytokine IL-1β, neuropeptide substance P (SP), nerve growth factor (NGF), and glial derived neurotrophic factor (GDNF) in peripheral and ganglion tissues, using a rat model of trigeminal neuropathic pain. Chronic constriction injury (CCI) of the infraorbital nerve (IoN), or a sham surgery, was performed. Mechanical allodynia was evaluated from day 3 to day 15 post-surgery. Trigeminal nerves were divided into 2 sections - distal to CCI and ganglion - for morphological analyses, immunohistochemistry (IL-1β, SP), and protein quantification by ELISA (NGF, GDNF). At early postoperative time points, decreased mechanical responses were observed, which were associated with demyelination, glial cell proliferation, increased immunoexpression of IL-1 β and SP, and impaired GDNF production. In the late postoperative period, mechanical allodynia was present with partial recovery of myelination, glial cell proliferation, and increased immunoreactivity of IL-1β and SP. Our data show that demyelination/remyelination processes are related to the development of pain behavior. IL-1β may have effects both in ganglia and nerves, while SP may be an important mediator at the nerve endings. Additionally, low levels of GDNF may produce impaired signaling, which may be involved in generation of pain.

Nitric oxide (NO) participates in neuronal lesions in the digestive form of Chagas disease and the proximity of parasitised glial cells and neurons in damaged myenteric ganglia is a frequent finding. Glial cells have crucial roles in many neuropathological situations and are potential sources of NO. Here, we investigate peripheral glial cell response to Trypanosoma cruzi infection to clarify the role of these cells in the neuronal lesion pathogenesis of Chagas disease. We used primary glial cell cultures from superior cervical ganglion to investigate cell activation and NO production after T. cruzi infection or lipopolysaccharide (LPS) exposure in comparison to peritoneal macrophages. T. cruzi infection was greater in glial cells, despite similar levels of NO production in both cell types. Glial cells responded similarly to T. cruzi and LPS, but were less responsive to LPS than macrophages were. Our observations contribute to the understanding of Chagas disease pathogenesis, as based on the high susceptibility of autonomic glial cells to T. cruzi infection with subsequent NO production. Moreover, our findings will facilitate future research into the immune responses and activation mechanisms of peripheral glial cells, which are important for understanding the paradoxical responses of this cell type in neuronal lesions and neuroprotection.

Introduction: The temporomandibular dysfunction (TMD) it’s a collective expression that encompasses clinical alterations in chewing muscles, temporomandibular joints (TMJ), and/or associated estructures. The viscosuplementation (VS) is a minimally invasive technique which consistis of intra-articular injection of sodium hyaluronate (SH) for the improvement of lubrification and joint biomechanics and elimination or decrease of pain. The aim of this study was to evaluate, through a series of cases, the efficacy of a viscosupplementation protocol with SH in different molecular weights, in the signs and syntptoms of joint TMJ and in patients’quality of life [1–3]. Materials and methods: this study was approved by the Ethics Committee of Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (CAAE-24911314.3.0000.5149) and registered in the Brazilian Registry of Clinical Trials (RBR-6759yz). Is a case series that describes the efficacy of a viscosupplementation protocol in intra-articular temporomandibular disorders. Ten patients with a diagnosis of disc displacement and/or osteoarthritis according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were submitted to four monthly injections of low or medium molecular weight HA. Pain, mandibular function, image analysis by tomography and magnetic resonance, and quality of life were assessed at baseline and follow-ups (1 and 6 months). Results: Pain, jaw range-of-motion, mandibular function, and quality of life improved at follow-up evaluations. Osteoarthritis changes decreased, and 20% of patients improved mandibular head excursion after treatment. Resolution of effusion and improvement in disc morphology were observed for most patients. This viscosupplementation protocol reduced pain and symptoms associated with internal derangement of temporomandibular joint, improved quality of life, and showed benefits from both low and medium molecular weight HA in alternate cycles. Discussion and conclusions: These results suggest the effectiveness of the VS protocol in the control and relief of the signs and symptoms of TMD, and the great therapeutic potential of this technique.

Introduction: Temporomandibular disorders (TMD) are a group of conditions that cause pain and dysfunction in temporomandibular joint (TMJ), masticatory muscles, and/or associated structures. Signs and symptoms include pain, joint sounds and/or joint dysfunction [1,2]. The aim of this study is to report the clinical case of a patient with TMD, articular disc sounds, associated with arthralgia. who underwent arthrocentesis with biodynamic irrigation and subsequent viscosupplementation in order to reestablish ATM biomechanics and promote pain relief. Materials and methods: Detailed clinical evaluation and examination of magnetic resonance imaging demonstrated an anterior displacement with the attachment of the TMJ disc to the posterior wall of the articular tubercle. This was accompanied by joint sound and severe pain (VAS =7), difficulty in chewing, as well as decreased interincisal distance (28.06 mm), which lingered for more than 5 years. Treatment consisted of arthrocentesis under local anesthesia without sedation, with two needles technique, using a total volume of 200 mL of saline solution followed by synovial fluid replacement with 10 mL of 0.5% 1200 kDa molecular weight sodium hyaluronate solution (Viscoseal®) under joint manipulation. After this procedure, 1 mL of 1% 1000-2000 kDa molecular weight sodium hyaluronate solution (Osteonil®) (viscosupplementation) was performed. Oral pharmacological control with non-steroidal anti-inflammatory and analgesic was also included. Results: Immediate results to therapy consisted of a increased mouth opening with a interincisal distance of 45.09 mm, reduction in joint sound, and restoration of mandibular movements. Supervised home physiotherapy was established in order to maintain function and mouth opening. The exercises were performed for 20 seconds, 3 times a day. After two months, significant progress was observed with gain of 17.03 mm in the interincisal distance, absence of pain (VAS = 0) and great decrease in right articular sound. Discussion and conclusions: Specifically in this case, this minimally invasive approach has shown successful clinical outcomes for arthralgia and biomechanical control of the temporomandibular joint. However, in the future, a larger case-control study is necessary to ascertain its promising potentialities

We developed a novel murine model of long-term infection with Trypanosoma cruzi with the aim to elucidate the pathogenesis of megacolon and the associated adaptive and neuromuscular intestinal disorders. Our intent was to produce a chronic stage of the disease since the early treatment should avoid 100% mortality of untreated animals at acute phase. Treatment allowed animals to be kept infected and alive in order to develop the chronic phase of infection with low parasitism as in human disease. A group of Swiss mice was infected with the Y strain of T. cruzi. At the 11th day after infection, a sub-group was euthanized (acute-phase group) and another sub-group was treated with benznidazole and euthanized 15 months after infection (chronic-phase group). Whole colon samples were harvested and used for studying the histopathology of the intestinal smooth muscle and the plasticity of the enteric nerves. In the acute phase, all animals presented inflammatory lesions associated with intense and diffuse parasitism of the muscular and submucosa layers, which were enlarged when compared with the controls. The occurrence of intense degenerative inflammatory changes and increased reticular fibers suggests inflammatory-induced necrosis of muscle cells. In the chronic phase, parasitism was insignificant; however, the architecture of Aüerbach plexuses was focally affected in the inflamed areas, and a significant decrease in the number of neurons and in the density of intramuscular nerve bundles was detected. Other changes observed included increased thickness of the colon wall, diffuse muscle cell hypertrophy, and increased collagen deposition, indicating early fibrosis in the damaged areas. Mast cell count significantly increased in the muscular layers. We propose a model for studying the long-term (15 months) pathogenesis of Chagasic megacolon in mice that mimics the human disease, which persists for several years and has not been fully elucidated. We hypothesize that the long-term inflammatory process mediates neuronal damage and intramuscular and intramural denervation, leading to phenotypic changes in smooth muscle cells associated with fibrosis. These long-term structural changes may represent the basic mechanism for the formation of the Chagasic megacolon.

Chagas disease is a chronic disorder caused by the Trypanosoma cruzi protozoan. The infection causes alterations to the enteric nervous system such as megaesophagus and megacolon. There is evidence of denervation of myenteric ganglia. The intense parasitism of acute phase affects neuronal integrity but contrasts with the absence of parasites and the discreet inflammatory process of chronic phase, indicating a progressive injury mechanism that needs to be better understood in the megacolons. The potential selectivity of enteric neurons classes affected by the progression of the disease is not yet clear. Nitrergic neurons which co-localize other neurotransmitters represent the most common inhibitory neuron of the ENS. Recently a chronic stage of the Chagas disease was reproduced experimentally in a suitable murine model of megacolon. Considering the limitation of studying human intestine and the controversy on the pattern of nNOS involvement in chagasic megacolon, we decided to assess the nitrergic neurons in the myenteric plexus of mice. We used antibodies against structural protein gene product 9.5 (PGP 9.5) and functional neuronal nitric oxide synthase (n-NOS) at the acute and chronic phase of the disease to quantify myenteric ganglionar neurons in the colon of infected and non-infected mice. We found a reduction in the ganglionar number of neurons detected by anti-protein gene product 9.5 antibodies in colon from mice at the chronic stage. However, the number of nitrergic neurons per ganglia remained unchanged along the acute to phase chronic of the disease. Our findings indicate a long-term preservation of nitregic neurons detrimental to other classes of enteric in our model of experimental Chagas disease. We propose that differential loss of enteric neurons is at least one of the structural substrate for the development of the longterm morphfunctional changes that lead to the megacolon.

Central nervous system glial cells as astrocytes and microglia have been investigated in vitro and many intracellular pathways have been clarified upon various stimuli. Peripheral glial cells, however, are not as deeply investigated in vitro despite its importance role in inflammatory and neurodegenerative diseases. Based on our previous experience of culturing neuronal cells, our objective was to standardize and morphologically characterize a primary culture of mouse superior cervical ganglion glial cells in order to obtain a useful tool to study peripheral glial cell biology. Superior cervical ganglia from neonatal C57BL6 mice were enzymatically and mechanically dissociated and cells were plated on diluted Matrigel coated wells in a final concentration of 10,000 cells/well. Five to 8 days post plating, glial cell cultures were fixed for morphological and immunocytochemical characterization. Glial cells showed a flat and irregular shape, two or three long cytoplasm processes, and round, oval or long shaped nuclei, with regular outline. Cell proliferation and mitosis were detected both qualitative and quantitatively. Glial cells were able to maintain their phenotype in our culture model including immunoreactivity against glial cell marker GFAP. This is the first description of immunocytochemical characterization of mouse sympathetic cervical ganglion glial cells in primary culture. This work discusses the uses and limitations of our model as a tool to study many aspects of peripheral glial cell biology.

Neuronal lesions and peripheral denervation in Chagas' disease are related to local inflammation; however, the pathogenic mechanisms of neuronal lesions in the heart and megavisceras are still unclear. We investigated the involvement of nitric oxide (NO) on neuronal lesion in co-cultures of neurons and macrophages. Trypanosoma cruzi-infected and interferon-gamma (IFN-gamma)-activated co-cultures of neurons and wild-type (WT) macrophages showed significant reduction of both neuronal survival and neurite density. These findings correlated with the levels of NO and the expression of inducible nitric oxide synthase (iNOS). Accordingly, neuronal survival rate in the co-cultures was recovered to control levels by treatment of the cultures with the iNOS inhibitor, aminoguanidine. Moreover, neither neuronal survival nor the neurite density was affected in the co-cultures when the macrophages were harvested from iNOS-deficient mice. These results demonstrate that iNOS-derived NO is the major molecule involved in neuronal damage mechanism in our in vitro model of Chagas' disease neuropathology.

BACKGROUND AND OBJECTIVES: Temporomandibular disorders are diseases causing pain and dysfunction in joints and muscles controlling mandibular movements. Their etiology is multifactorial and multidisciplinary approaches are needed to reach a differential diagnosis and an adequate management plan. This case report proposes a management protocol, with monthly sodium hyaluronate infiltrations, with different molecular weights, to control such changes and promote improvement of temporomandibular joint biomechanics and pain. CASE REPORT: This study describes a case of a 48-year old patient with a 10-year history of temporomandibular pain with function loss since 2001. Patient has classified her pain as 9 according to analog visual scale. In addition, history and detailed physical evaluation have shown different signs and symptoms, such as localized pain (right side), and right temporomandibular joint arthralgia with noise. Diagnosis was disc displacement with reduction and possible synovitis/ capsulitis to the right. Right temporomandibular joint osteoarthritis was also diagnosed by cone beam CT-scan. Initially, a flat upper splint with total coverage and contact with all antagonist teeth was used. In the attempt to decrease temporomandibular arthralgia, non-steroid anti-inflammatory drugs and muscle relaxants were used. Since right temporomandibular joint pain was not effectively managed, we decided to use intra-joint sodium hyaluronate injections with different molecular weights, per month, in a total of four applications. At treatment completion, clinical evaluation has shown normal function, no pain with visual analog scale = zero, in addition to adequate interincisal distance. CONCLUSION: This report has suggested that viscosupplementation cycles with sodium hyaluronate of different molecular weights may provide excellent results in the long run, to control joint temporomandibular disorder symptoms. Therapeutic benefits were maintained for four years with no need for annual maintenance cycles.

Trypanosoma cruzi infection induces progressive cardiac inflammation that leads to fibrosis and modifications in the heart architecture and functionality. Statins, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have been studied due to their pleiotropic roles in modulating the inflammatory response. Our goal was to evaluate the effects of simvastatin on the cardiac inflammatory process using a cardiotropic strain of T. cruzi in a murine model of Chagas cardiomyopathy. C57BL/6 mice were infected with 500 trypomastigotes of the Colombian strain of T. cruzi and treated with an oral dose of simvastatin (20 mg/Kg/day) for one month and inflam-matory and morphometric parameters were subsequently evaluated in the serum and in the heart, respectively. Simvastatin reduced the total cholesterol and inflammatory mediators (interferon-gamma, tumour necrosis factor-alpha, CCL2 and CCL5) in the serum and in the heart tissue at 30 days post-infection. Additionally, a proportional reduction in heart weight and inflammatory infiltration was observed. Simvastatin also reduced epimastigote pro¬liferation in a dose-dependent manner in vitro and was able to reduce blood trypomastigotes and heart amastigote nests during the acute phase of Chagas disease in vivo. Based on these data, we conclude that simvastatin exerts a modulatory effect on the inflammatory mediators that are elicited by the Colombian strain of T. cruzi and amelio¬rates the heart damage that is observed in a murine model of Chagas disease.

The family Poxviridae comprises the most complex animal DNA viruses. During some poxvirus infections, A-type inclusion bodies (ATIs), codified by the ati gene, are produced. Although some studies have compared poxviruses that encode these inclusion bodies with those that do not, the biological function of ATIs is poorly understood. A recombinant ati-deleted cowpox virus was constructed and compared with the wild-type virus in in vitro experiments including electron microscopy and plaque and viral growth assays. No significant differences were observed in vitro. This reinforces the conclusion that the inclusion body is not essential for in vitro viral replication and morphogenesis. Additionally, different lesion progressions in vivo were observed by macroscopic and histological analysis, suggesting that the presence or absence of ATIs could result in different healing dynamics. This is the first time that the role of ATIs during viral replication has been studied based solely on one variable, the presence or absence of ATIs.

Brazilian Vaccinia virus had been isolated from sentinel mice, rodents and recently from humans, cows and calves during outbreaks on dairy farms in several rural areas in Brazil, leading to high economic and social impact. Some phylogenetic studies have demonstrated the existence of two different populations of Brazilian Vaccinia virus strains circulating in nature, but little is known about their biological characteristics. Therefore, our goal was to study the virulence pattern of seven Brazilian Vaccinia virus strains. Infected BALB/c mice were monitored for morbidity, mortality and viral replication in organs as trachea, lungs, heart, kidneys, liver, brain and spleen. Based on the virulence potential, the Brazilian Vaccinia virus strains were grouped into two groups. One group contained GP1V, VBH, SAV and BAV which caused disease and death in infected mice and the second one included ARAV, GP2V and PSTV which did not cause any clinical signals or death in infected BALB/ c mice. The subdivision of Brazilian Vaccinia virus strains into two groups is in agreement with previous genetic studies. Those data reinforce the existence of different populations circulating in Brazil regarding the genetic and virulence characteristics.

Background The clinical presentation of dengue is classified by the World Health Organization into dengue without warning signs, dengue with warning signs and severe dengue. Reports of neurological disease caused by Dengue virus (DENV) are becoming frequent, with symptoms that include reduced consciousness, severe headache, neck stiffness, focal neurological signs, tense fontanelle and convulsions. However, the immune mechanisms involved in neurovirulence remain poorly understood. Here we present a mouse model in which one genotype of DENV is inoculated by the intracranial route and infects C57/BL6 mice and replicates in the brain, causing death of mice. Methods Mice were infected with different serotypes/genotypes of DENV by the intracranial route to evaluate viral replication, host cytokine and nitric oxide synthase 2 (Nos2) expression in the brain via real-time PCR. Histological analysis of the brain tissues was also performed. An analysis of which cells were responsible for the expression of cytokines and Nos2 was performed using flow cytometry. Survival curves of infected animals were also generated Results DENV 3 genotype I infected mice and replicated in the brain, causing death in our murine model. The increased levels of NOS2 could be the cause of the death of infected mice, as viral replication correlates with increased Nos2 and cytokine expression in the brain of C57BL/6 mice. In Nos2 −/− mice that were infected with DENV, no clinical signs of infection were observed and cytokines were expressed at low levels, with the exception of interferon gamma (Ifng). Additionally, the Ifng −/− mice infected with DENV exhibited a severe and lethal disease, similar to the disease observed in C57BL/6 mice, while the DENV- infected Nos2 −/− mice did not display increased mortality. Analyses of the brains from infected C57BL/6 mice revealed neuronal degeneration and necrosis during histopathologic examination. IFNg and NOS2 were produced in the brains of infected mice by CD4+ T cells and macrophages, respectively. Conclusion The neurovirulence of DENV 3 genotype I is associated with a deleterious role of NOS2 in the brain, confirming this murine model as an appropriate tool to study DENV neurovirulence.