Efeito antinociceptivo da maresina-2 em modelos animais de dor pós operatória e neuropática trigeminal

Orientadora: Profa. Dra. Juliana Geremias ChichorroDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Farmacologia. Defesa : Curitiba, 23/09/2021Inclui referências: p. 48-56Resumo: A dor é um sintoma comum associado a distúrbios que envolvem as estruturas orofaciais. A maioria das condições dolorosas orofaciais agudas são facilmente reconhecidas, mas o tratamento farmacológico pode ser limitado pelos eventos adversos dos fármacos atualmente disponíveis e/ou pelas características dos pacientes. Além disso, as condições de dor orofacial crônica representam desafios clínicos tanto em termos de diagnóstico quanto de tratamento. Sendo assim, torna-se importante a busca de novas alternativas terapêuticas, as quais contornem as limitações existentes. Nesse sentido, evidenciam-se os lipídeos pró-resolução especializados (do inglês, SPMs, specialized pro-resolving mediators) como uma alternativa promissora de tratamento no controle do processo inflamatório e de outras doenças. Esses mediadores químicos endógenos são biossintetizados na fase de resolução da inflamação, e agem modulando a resposta imune do indivíduo ao interagir com receptores acoplados a proteína G presentes em células de defesa e de neurônios. Além de seus efeitos anti-inflamatórios e pró-resolução, há evidências crescentes de que os SPMs podem atuar reduzindo a severidade de outras condições patológicas, entre elas doenças degenerativas, depressão, infecções, dores inflamatórias e crônicas. Em relação ao seu potencial analgésico, foram relatados potentes e prolongados efeitos antialodínicos e antihiperalgésicos para alguns desses lipídeos, em especial para a maresina-1 (MaR-1). Contudo, embora semelhantes quimicamente, não se encontram estudos que descrevam esses efeitos também para a maresina-2 (MaR-2). O presente trabalho teve como objetivo investigar o potencial antinociceptivo da Maresina-2 (MaR-2) em modelos de dor orofacial. O teste de formalina foi realizado em ratos de acordo com trabalhos anteriores realizados por nosso grupo, com o objetivo de obter um screening do efeito analgésico da MaR-2. A cirurgia de incisão intraoral (INC) em ratos e a constrição do nervo infraorbital em ratos e camundongos (CCI-ION) foram realizadas conforme publicações anteriores do nosso grupo. O tratamento com Maresina-2 (10 ng) foi feito em dias alternados após o procedimento cirúrgico, totalizando 2 injeções no modelo de INC e 4 injeções no modelo de CCI-ION, sempre via medular subaracnóidea. Foram avaliadas a hiperalgesia térmica e mecânica em dias alternados, até 2 dias após o término dos tratamentos. A atividade neuronal foi avaliada através de imunofluorescência para c- Fos e CGRP em camundongos. Uma única injeção de MaR-2 causou redução significativa do grooming facial nas fases I e II do teste de formalina orofacial em ratos. Injeções repetidas de MaR-2 preveniram o desenvolvimento de hiperalgesia ao calor e hiperalgesia mecânica em um modelo de dor pós-operatória em ratos. Em um modelo de dor neuropática trigeminal (i.e., cirurgia de constrição crônica do nervo infraorbital, CCI-ION), o tratamento repetido com MaR-2 reverteu a hiperalgesia térmica e a hiperalgesia mecânica em ratos e camundongos. A CCI-ION causou aumento de neurônios c-Fos positivos e dos neurônios ativados por CGRP no gânglio trigeminal (TG), que foram restaurados aos níveis basais pelo tratamento repetido com MaR-2. Em conclusão, a MaR-2 tem efeitos analgésicos potentes e de longa duração na dor inflamatória e neuropática de origem orofacial, e a inibição da atividade de neurônios CGRP-positivos no TG pode contribuir para o efeito analgésico da MaR-2.Abstract: Pain is a common symptom associated with disorders involving orofacialstructures. Most acute orofacial painful conditions are easily recognized, butpharmacological treatment may be limited by adverse events of currently availabledrugs and/or patient characteristics. In addition, chronic orofacial pain conditions poseclinical challenges both in terms of diagnosis and treatment. Therefore, it is importantto search for new therapeutic alternatives, which overcome the existing limitations. Inthis sense, specialized pro-resolving lipids (SPMs, specialized pro-resolvingmediators) are evidenced as a promising alternative treatment for the control of theinflammatory process and other diseases. These endogenous chemical mediators arebiosynthesized in the inflammation resolution phase and act by modulating theindividual's immune response by interacting with G protein-coupled receptors presentin defense e is growing evidence that PMS can act to reduce the severity of otherpathological cells and neurons. In addition to their anti-inflammatory and pro-resolutioneffects, therconditions, including degenerative diseases, depression, infections,inflammatory and chronic pain. Regarding its analgesic potential, potent and prolongedanti allodynic and anti hyperalgesic effects have been reported for some of these lipids,especially for maresin-1 (MaR-1). However, although chemically similar, there are nostudies that describe these effects also for maresin-2 (MaR-2). This study aimed toinvestigate the antinociceptive potential of Maresin-2 (MaR-2) in orofacial pain models.The formalin test was performed in rats by previous work carried out by our group, toobtain a screening of the analgesic effect of MaR-2. Intraoral incision surgery (INC) inrats and constriction of the infraorbital nerve in rats and mice (ICC-ION) wereperformed according to previous publications from our group. Treatment with Maresin-2 (10 ng) was performed every other day after the surgical procedure, totaling 2injections in the INC model and 4 injections in the CCI-ION model, always via the spinalcord. Thermal and mechanical hyperalgesia was evaluated on alternate days, up to 2days after the end of treatments. Neuronal activity was evaluated byimmunofluorescence for c-Fos and CGRP in mice. A single MaR-2 injection caused asignificant reduction in facial grooming in phases I and II of the orofacial formalin testin rats. Repeated MaR-2 injections prevented the development of heat hyperalgesiaand mechanical hyperalgesia in a postoperative pain model in rats. In a model oftrigeminal neuropathic pain (i.e., surgery for chronic infraorbital nerve constriction, CCIION),repeated treatment with MaR-2 reversed thermal hyperalgesia and mechanicalhyperalgesia in rats and mice. CCI-ION caused an increase in c-Fos positive neuronsand CGRP-activated neurons in the trigeminal ganglion (TG), which were restored tobaseline levels by repeated treatment with MaR-2. In conclusion, MaR-2 has potentand long-lasting analgesic effects on inflammatory and neuropathic pain of orofacialorigin, and inhibition of the activity of CGRP-positive neurons in TG may contribute tothe analgesic effect of MaR-2

Antinociceptive and anxiolytic-like effects of Lavandula angustifolia essential oil on rat models of orofacial pain

Nociceptive and inflammatory orofacial pain is highly prevalent in the population, which justifies the search for safer analgesics. There is increasing evidence of the analgesic and anxiolytic potential of Lavandula angustifolia essential oil (LAV EO), which may represent, when administered through inhalation, may represent a safer alternative for pain treatment. Objective: to evaluate whether LAV EO has antinociceptive effect in the formalin test, and anti-hyperalgesic and anxiolytic-like effects in rats subjected to a model of orofacial postoperative pain. Methodology: Female Wistar rats were exposed to LAV EO (5%) by inhalation for 30 minutes. After exposure, animals were injected with formalin (2.5%, 50 μL) or saline into the hind paw or upper lip and the number of flinches or facial grooming time, respectively, were evaluated. Likewise, on day 3 after intraoral mucosa incision, the animals were exposed to LAV EO and facial mechanical, and heat hyperalgesia were assessed. The influence of LAV EO inhalation on anxiety-like behavior was assessed in operated rats by testing them on the open field (OF) and elevated plus maze (EPM). Results: LAV EO reduced the phase II of the paw formalin test and both phases of the orofacial formalin test. On day three post-incision, LAV EO reduced heat and mechanical hyperalgesia, from 30 minutes up to three hours, and reduced the anxiety-like behavior in operated rats without causing locomotor deficit. Conclusion: LAV EO inhalation results in antinociceptive and anxiolytic-like effects in orofacial pain models, which encourages further studies on LAV EO indications and effectiveness on orofacial pain conditions

A Representação Feminina nas Campanhas Antitabagistas do Ministério da Saúde

O consumo do tabaco é responsável por grande parte da mortalidade evitável no mundo. Neste contexto, existe um intenso esforço do Governo Federal Brasileiro em promover a saúde pública por meio da implantação de estratégias de comunicação antitabagistas do Ministério da Saúde. Dados atuais mostram que há uma menor redução no número de mulheres fumantes, com relação aos homens, após o início das veiculações de imagens de Advertências Sanitárias nos Produtos de Tabaco. Por essa ótica, o presente trabalho busca analisar de que maneira as teorias relativas às identidades, abordando questões de identificação e pertencimento, podem ser importantes ao propor campanhas de comunicação que visam promover uma mobilização social em prol desta causa, com foco nas representações do gênero feminino. PALAVRAS-CHAVE: Identidade, Questões de Gênero, tabagismo, Saúde, Comunicação

Solid Waste And Its Interference On The Water Quality Of The Igarapé¹ do Quarenta Educandos Basin - Manaus/Am

The “Igarapé do Quarenta”, a stream in Educandos basin, is categorized today as the "worst" and most polluted of the city Manaus, Amazonas, due to the accumulation of solid waste and contamination by heavy metals along its course. The main objective of this research was to verify the influence of solid waste in critical points of the Igarapé do Quarenta, on the water quality of the stream. The area of solid waste accumulation ("garbage") and the water quality in the stream and around and under the bridges of the Igarapé do Quarenta, between the springs (Armando Mendes and Zumbi neighborhoods) and the mouth (Educandos), in the Amazon "summer" and "winter"," were quantified. Water quality was evaluated at each sampling site. The macroscopic analysis demonstrated its importance for the feasibility diagnosis, finding that two of the three springs found are degraded and disturbed. The pH and electrical conductivity values in the sample sites visited, in the upper and middle, of the Igarapé do Quarenta, were very high values in relation to the maximum values recorded in a natural environment in other water streams of Manaus

Escore de Cálcio Coronariano na estratificação do risco cardiovascular: uma revisão de literatura

INTRODUÇÃO: O Escore de Cálcio Coronariano tem sido amplamente utilizado para estratificação de risco cardiovascular em pacientes assintomáticos. Sua utilização favorece decisões a respeito de medidas preventivas. OBJETIVO: Avaliar as aplicações do Escore Coronariano de Cálcio e sua relação com a estratificação de risco cardiovascular. MÉTODOS: Trata-se de uma revisão integrativa na base de dados PUBMED utilizando os descritores “Calcium score coronary AND ardiovascular risk AND stratification’’ para artigos publicados e 2018 e 2023. RESULTADOS: dos 127 artigos encontrados, 9 contemplavam o tema. A utilização do Escore de Cálcio Coronariano tem ocorrido em diversas situações se correlacionando o risco cardiovascular com outros fatores de risco, como em fumantes, pacientes com histórico de acidente vascular encefálico, hipertensos e aqueles com dor torácica. Pacientes com escore 0 possuem risco 1,4 vezes menor de apresentar algum tipo de evento cardiovascular em comparação aqueles maiores que 1. CONCLUSÃO: o uso do escore deve ser estimulad, assim como as correlações entre os valores e outros fatores de risco para eventos cardiovasculares

PRINCIPAIS ALTERAÇÕES NO ELETROCARDIOGRAMA EM CÃES

The electrocardiogram (ECG) is considered the most widely used method of diagnosis of cardiac diseases in veterinary medicine, being a dynamic and non-invasive evaluation of the heart. The electric waves are evaluated through the characteristics of duration, amplitude and deflection that can vary according to the species, size, sex, age and race of the animal. The knowledge of the prevalence of cardiac affections in dogs is of fundamental importance for the clinician of small animals, as it assists in the formulation of differential diagnoses and in the establishment of an adequate therapeutic plan. Thus, the objective of this study is to present the frequency of the main alterations in the electrocardiogram in dogs attended by the electrocardiography service of the ETAVE Veterinary Hospital of Fortaleza, Ceará. The sample consisted of 518 dogs, of these 216 males and 352 females, attended at the Veterinary Hospital - ETAVE of Fortaleza - CE, from September 2016 to September 2018. The animals were selected from the clinical indication, anesthetic and pre-surgical, being submitted to physical and clinical avaliation. Thus, we conclude that the changes most frequently found were low-amplitude QRS complex, first-degree atrioventricular block, and premature supraventricular tachycardia, present in at least two of the groups of alterations studied. The ECG is an important diagnostic feature that can help both detect and control cardiac conditions, which, if uncontrolled and treated, can lead to death.O eletrocardiograma (ECG) é considerado o método de auxílio ao diagnóstico das afecções cardíacas mais utilizado na medicina veterinária, sendo dinâmico e não-invasivo de avaliação do coração. São avaliadas as ondas elétricas através das características de duração, amplitude e deflexão que podem variar de acordo com a espécie, porte, sexo, idade e raça do animal. O conhecimento da prevalência das afecções cardíacas em cães é de fundamental importância para o clínico de pequenos animais, pois auxilia na formulação de diagnósticos diferenciais e no estabelecimento de um plano terapêutico adequado. Assim, o objetivo deste trabalho é apresentar a frequência das principais alterações no eletrocardiograma de cães atendidos pelo serviço de eletrocardiografia do Hospital Veterinário ETAVE de Fortaleza, Ceará. A amostra foi composta por 518 cães, destes, 216 machos e 352 fêmeas, atendidos no Hospital Veterinário – ETAVE de Fortaleza - CE, no período de setembro de 2016 a setembro de 2018. Os animais foram selecionados a partir da indicação clínica, exame pré-anestésico e pré-cirúrgico, sendo submetidos a avaliação física e clínica. Com isso, conclui-se que as alterações mais frequentemente encontradas foram, complexo QRS de baixa amplitude, bloqueio atrioventricular de 1º grau e taquicardia supraventricular prematura, presentes em pelo menos dois dos grupos de alterações estudados. O ECG é um importante recurso diagnóstico que pode ajudar tanto na detecção quanto no controle das afecções cardíacas, que se não controladas e tratadas podem levar o animal à morte

Biofortificação agronômica de grãos de feijão com zinco

The objective of this work was to evaluate the effects of the split and combinated application of foliar zinc (ZnF) + soil Zn (ZnS) on Zn concentration in the grains (ZnCG) of common bean (Phaseolus vulgaris). Two experiments were carried out in a greenhouse during two seasons. In the first experiment, two common bean cultivars received six ZnF rates (0, 120, 240, 480, 720, or 1,200 g ha-1), with split applications at the R5, R7, and R8, or R7 and R8, or R8 plant stages. In the second experiment, one cultivar received three ZnS rates (0, 5, or 10 kg ha-1) combined with ZnF rates (0, 1, 1.5, 3, 6, or 10 kg ha-1). In the first experiment, with the ZnF increment, ZnCG increased linearly from 15.3 to 20.7 mg kg-1. ZnF splitting did not affect ZnCG. In the second experiment, ZnF without ZnS did not affect ZnCG. ZnS doubled ZnCG in comparison with the treatment without ZnS application. At 5 kg ha-1 ZnS, the highest ZnCG (67.5 mg kg-1) was obtained with 7.8 kg ha-1 ZnF. At 10 kg ha-1, the highest ZnCG (66 mg kg-1) was obtained with 4.9 kg ha-1 ZnF. ZnF splitting is not advantageous over a single application, and the combination of ZnF and ZnS increases ZnCG in common bean, in greenhouse conditions.O objetivo deste trabalho foi avaliar os efeitos da aplicação parcelada e combinada de zinco foliar (ZnF) + Zn no solo (ZnS) sobre o teor de Zn dos grãos (TZnG) do feijão-comum (Phaseolus vulgaris). Dois experimentos foram realizados em casa de vegetação durante dois períodos. No primeiro experimento, duas cultivares de feijão-comum receberam seis doses de ZnF (0, 120, 240, 480, 720, ou 1.200 g ha-1), com aplicações parceladas nos estágios da planta R5, R7 e R8, ou R7 e R8, ou R8. No segundo experimento, uma cultivar recebeu três doses de ZnS (0, 5 ou 10 kg ha-1) combinadas com doses de ZnF (0, 1, 1,5, 3, 6 ou 10 kg ha-1). No primeiro experimento, com o incremento do ZnF, o TZnG aumentou linearmente de 15,3 para 20,7 mg kg-1. O parcelamento do ZnF não afetou o TZnG. No segundo experimento, o ZnF sem o ZnS não afetou o TZnG. O ZnS dobrou o TZnG em comparação ao tratamento sem aplicação de ZnS. Com 5 kg ha-1 de ZnS, o mais alto TZnG (67,5 mg kg-1) foi obtido com 7,8 kg ha-1 de ZnF. Com 10 kg ha-1, o mais alto TZnG (66,0 mg kg-1) foi obtido com 4,9 kg ha-1 de ZnF. O parcelamento do ZnF não é vantajoso em relação à aplicação única, e a combinação ZnF e ZnS aumenta o TZnG do feijão-comum em casa de vegetação

Technical and economic efficiency of bovine weighing methods

The objective of this study was to evaluate the technical and economic efficiency of different methods of cattle weighing, and to develop mathematical equations to estimate the breakeven point for the adoption of electronic weighing, i.e., to estimate how many animals are required for the acquisition and use of an electronic scale to be economically viable. The survey was conducted in confined beef cattle, from the Federal Institute of Education, Science and Technology in the south of Minas Gerais, IFSUL DE MINAS, Muzambinho Campus, from July to December 2014. Two methods of weighing cattle were evaluated: an electronic scale and a tape measure, using a barimetric tape for dairy cattle and a barimetric tape for beef cattle, and a conventional tape measure involving the conversion of centimeters into body weight using a specific table. Thirty-three animals identified with plastic ear tags were weighed using each method. Animals of the Nellore, Senepol, Girolando, and Red-angus breeds, aged 0–1, 1–2, and 2–3 years, were weighed 402 times in total. The time taken to weigh animals with the electronic scale was the lowest, followed by that with the barimetric tape, and that with conventional tape measure with conversion. The electronic scale exhibited the greatest technical efficiency, owing to the lack of error and the lowest time required to weigh animals. However, the costs associated with the use of this equipment were the highest, which depended on the purchasing cost. The mathematical equations developed will help technicians and cattle farmers to rapidly and precisely estimate the minimum number of animals that should compose a production system to ensure economic viability for the adoption of an electronic method to weigh cattle

THYROID CANCER: CLINICAL EVALUATION, ENDOCRINOLOGICAL MANIFESTATIONS AND SURGICAL MANAGEMENT

Thyroid cancer is more common in women and people over 40, but it can affect anyone. There are different types of thyroid cancer, the most common being differentiated carcinomas (papillary and follicular), which have a good prognosis and respond well to treatment. The clinical evaluation of thyroid cancer involves taking anamnesis, physical examination, measuring thyroid hormones and performing imaging tests and biopsy. The main symptom of thyroid cancer is the appearance of a nodule in the cervical region, which may be palpable or visible. The main surgical modalities are total thyroidectomy, which consists of complete removal of the thyroid gland; partial thyroidectomy or lobectomy, which consists of removing only part of the gland; and lymphadenectomy, which consists of removing lymph nodes affected by cancer. Objective: to synthesize the scientific evidence available on clinical assessment, endocrinological manifestations and surgical management in thyroid cancer. Methodology: based on the PRISMA checklist, the PubMed, Scielo and Web of Science databases were consulted to identify relevant studies published in the last 10 years. The descriptors used were: “thyroid cancer”, “thyroid neoplasm”, “clinical evaluation”, “surgical management” and “endocrinological manifestations”. Original studies in English or Portuguese that addressed the clinical, endocrinological or surgical aspects of thyroid cancer in humans were included. Studies that did not meet the inclusion criteria, were duplicates, had low methodological quality or did not have access to the full text were excluded. Results: 18 studies were selected, which revealed that thyroid cancer is a disease that presents different clinical, endocrinological and surgical aspects, depending on the type, stage and response to treatment. The studies analyzed provided evidence on diagnostic methods, indications and surgical techniques, the efficacy and safety of radioactive iodine therapy, and the role of suppressive hormone therapy in differentiated thyroid cancer. Conclusion: Thyroid cancer is a heterogeneous disease that requires a multidisciplinary approach for its diagnosis and treatment. The systematic review showed that there is consistent evidence on diagnostic methods, surgical modalities and radioactive iodine therapy in differentiated thyroid cancer. However, there are gaps in knowledge about the endocrinological manifestations of thyroid cancer and therapeutic alternatives for more complex or aggressive cases. Therefore, more studies are needed to clarify these aspects and improve the clinical management of patients with thyroid cancer.Thyroid cancer is more common in women and people over 40, but it can affect anyone. There are different types of thyroid cancer, the most common being differentiated carcinomas (papillary and follicular), which have a good prognosis and respond well to treatment. The clinical evaluation of thyroid cancer involves taking anamnesis, physical examination, measuring thyroid hormones and performing imaging tests and biopsy. The main symptom of thyroid cancer is the appearance of a nodule in the cervical region, which may be palpable or visible. The main surgical modalities are total thyroidectomy, which consists of complete removal of the thyroid gland; partial thyroidectomy or lobectomy, which consists of removing only part of the gland; and lymphadenectomy, which consists of removing lymph nodes affected by cancer. Objective: to synthesize the scientific evidence available on clinical assessment, endocrinological manifestations and surgical management in thyroid cancer. Methodology: based on the PRISMA checklist, the PubMed, Scielo and Web of Science databases were consulted to identify relevant studies published in the last 10 years. The descriptors used were: “thyroid cancer”, “thyroid neoplasm”, “clinical evaluation”, “surgical management” and “endocrinological manifestations”. Original studies in English or Portuguese that addressed the clinical, endocrinological or surgical aspects of thyroid cancer in humans were included. Studies that did not meet the inclusion criteria, were duplicates, had low methodological quality or did not have access to the full text were excluded. Results: 18 studies were selected, which revealed that thyroid cancer is a disease that presents different clinical, endocrinological and surgical aspects, depending on the type, stage and response to treatment. The studies analyzed provided evidence on diagnostic methods, indications and surgical techniques, the efficacy and safety of radioactive iodine therapy, and the role of suppressive hormone therapy in differentiated thyroid cancer. Conclusion: Thyroid cancer is a heterogeneous disease that requires a multidisciplinary approach for its diagnosis and treatment. The systematic review showed that there is consistent evidence on diagnostic methods, surgical modalities and radioactive iodine therapy in differentiated thyroid cancer. However, there are gaps in knowledge about the endocrinological manifestations of thyroid cancer and therapeutic alternatives for more complex or aggressive cases. Therefore, more studies are needed to clarify these aspects and improve the clinical management of patients with thyroid cancer