As the principal pro-inflammatory prostanoid, prostaglandin E2 (PGE2) serves as mediator of pain and fever in inflammatory reactions. The biosynthesis of PGE2 starts from arachidonic acid (AA). Cyclooxygenase (COX)-1 and/or COX-2 converts AA to prostaglandin H2 (PGH2), and PGE2 synthases transform PGH2 to PGE2. Current mainstream approach for treating inflammation-related symptoms remains the application of traditional non-steroidal anti-inflammatory drugs (tNSAIDs) and selective COX-2 inhibitors (coxibs). As both categories shut down the biosynthesis of all downstream prostanoids, their application renders several deleterious effects including gastrointestinalulceration and cardiovascular risk. Microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors, specifically blocking the production of inflammation-related PGE2, are expected to reduce the adverse effects while retain the anti-inflammation activity. Although several compounds have been reported, only a few have entered clinical trials and none was on the market. Particularly, most of the reported human mPGES-1 inhibitors were not active for wild-type mouse/rat mPGES-1 enzymes, which prevents using the well-established mouse/rat models of inflammation in preclinical studies. Therefore, we expect our designed inhibitors to also be potent against mouse mPGES-1 and thus is suitable for preclinical testing in wild-type mice.

The overall goal of this thesis is to better understand mechanisms governing associative phase separation within admixtures of plant proteins (e.g., pea and canola) and anionic polysaccharides (e.g., gum Arabic, alginate or é-carrageenan). The process involves the electrostatic attraction between two biopolymers of opposing charges, and typically results in the formation of both soluble and insoluble complexes during an acidic pH titration. If successful, polysaccharides could be triggered to coat the proteins surface to give novel, and hopefully improved functionality as ingredients for food and biomaterials.<p> In the first study, the effect of protein enrichment and pH on the formation of soluble and insoluble complexes in admixtures of pea legumin (Lg) and vicilin (Vn) isolates with gum Arabic (GA) was investigated by turbidimetric, surface charge and fluorometric measurements. The solubility of the protein isolates and mixed biopolymer systems was also studied as a function of pH. Enrichment of the crude Lg and Vn isolates by low pressure liquid chromatography led to a shift towards higher pHs at the onset of soluble complex formation in the presence of GA for both protein isolates, whereas the onset of insoluble complex formation was unaffected. Complexation of the Lg (or Vn) isolates with GA resulted in a shift in the pH where neutrality (zeta potential = 0 mV) occurred to lower pH values, relative to the Lg (or Vn) isolates alone. In the case of the enriched Vn isloate, changes to its tertiary structure were observed by fluorometry upon complexation with GA, whereas no changes were found for the enriched Lg isolate. Complexation of Lg and Vn isolates with GA also had little effect on their solubilities relative to protein alone solutions.<p> In the second study, the formation of soluble and insoluble complexes, and the nature of their interactions as determined by optical density analysis, were investigated in admixtures of canola protein isolate (CPI) and anionic polysaccharides (alginate and é-carrageenan) as a function of pH and biopolymer weight mixing ratio. The solubilities of formed complexes were also investigated versus protein alone. In both CPI-polysaccharide systems, critical pH associated with the onset of soluble and insoluble complexes shifted to higher pHs as the mixing ratios increased from 1:1 to 20:1 (CPI:polysaccharide), and then became constant. There complexes formed primarily through electrostatic attractive forces with secondary stabilization by hydrogen bonding. The solubilities of the CPI-alginate complexes were significantly enhanced relative to CPI alone or CPI-é-carrageenan, which were similar.

The overall goal of this thesis is to better understand mechanisms governing associative phase separation within admixtures of plant proteins (e.g., pea and canola) and anionic polysaccharides (e.g., gum Arabic, alginate or é-carrageenan). The process involves the electrostatic attraction between two biopolymers of opposing charges, and typically results in the formation of both soluble and insoluble complexes during an acidic pH titration. If successful, polysaccharides could be triggered to coat the proteins surface to give novel, and hopefully improved functionality as ingredients for food and biomaterials.<p> In the first study, the effect of protein enrichment and pH on the formation of soluble and insoluble complexes in admixtures of pea legumin (Lg) and vicilin (Vn) isolates with gum Arabic (GA) was investigated by turbidimetric, surface charge and fluorometric measurements. The solubility of the protein isolates and mixed biopolymer systems was also studied as a function of pH. Enrichment of the crude Lg and Vn isolates by low pressure liquid chromatography led to a shift towards higher pHs at the onset of soluble complex formation in the presence of GA for both protein isolates, whereas the onset of insoluble complex formation was unaffected. Complexation of the Lg (or Vn) isolates with GA resulted in a shift in the pH where neutrality (zeta potential = 0 mV) occurred to lower pH values, relative to the Lg (or Vn) isolates alone. In the case of the enriched Vn isloate, changes to its tertiary structure were observed by fluorometry upon complexation with GA, whereas no changes were found for the enriched Lg isolate. Complexation of Lg and Vn isolates with GA also had little effect on their solubilities relative to protein alone solutions.<p> In the second study, the formation of soluble and insoluble complexes, and the nature of their interactions as determined by optical density analysis, were investigated in admixtures of canola protein isolate (CPI) and anionic polysaccharides (alginate and é-carrageenan) as a function of pH and biopolymer weight mixing ratio. The solubilities of formed complexes were also investigated versus protein alone. In both CPI-polysaccharide systems, critical pH associated with the onset of soluble and insoluble complexes shifted to higher pHs as the mixing ratios increased from 1:1 to 20:1 (CPI:polysaccharide), and then became constant. There complexes formed primarily through electrostatic attractive forces with secondary stabilization by hydrogen bonding. The solubilities of the CPI-alginate complexes were significantly enhanced relative to CPI alone or CPI-é-carrageenan, which were similar.

Thesis (M.Sc. (Pharmacology))--Mahidol University, 1986.

Evidências demonstram que ambas as isoformas da ciclooxigenase (COX) são constitutivamente expressas na medula espinhal (ME) de ratos, sendo COX-2 predominante no corno dorsal da medula espinhal (CDME) e podendo apresentar importante papel no desenvolvimento e manutenção da dor inflamatória. Assim, sugerese que os antiinflamatórios não-esteroidais (AINEs) possam exercer sua ação analgésica diretamente sobre o sistema nervoso central (SNC), e a administração espinhal desses fármacos tem despontado como uma alternativa no manejo da dor. O presente estudo objetiva, portanto, avaliar os efeitos da administração subaracnóidea (SA) do meloxicam em um modelo de dor inflamatória, bem como sua possível toxicidade sobre o SNC. Foram utilizados 27 ratos Wistar, machos, nos quais uma cânula SA foi implantada. Os animais foram aleatoriamente distribuídos em três grupos e submetidos à administração de 5 L de solução salina (Grupo I – GI), 30 g de meloxicam (Grupo II – GII) ou somente à manutenção crônica da cânula SA (Grupo III – GIII). A hipernocicepção mecânica foi induzida pela injeção intraplantar de carragenina e avaliada com o emprego de um analgesímetro digital durante um período de 4 horas. Para estudo da neurotoxicidade, os animais foram diariamente avaliados quanto ao peso corporal, alterações comportamentais e funções neurológicas, sendo mortos por perfusão transcardíaca um, sete ou 14 dias após a implantação da cânula SA. A ME foi coletada e submetida à análise histopatológica. Os resultados demonstraram que a administração do meloxicam na dose de 30 g.animal-1 não foi capaz de suprimir a resposta hipernociceptiva mecânica induzida pela carragenina. Nenhum animal, contudo, apresentou qualquer alteração comportamental ou das funções neurológicas durante o período de observação, tampouco ocorrendo diferença na variação do peso corporal entre os grupos. A análise histopatológica da ME não apresentou diferenças entre os grupos experimentais, entretanto revelou a presença de alterações severas relacionadas à presença da cânula SA, especialmente na região cervical. Estes dados sugerem a ausência de efeitos neurotóxicos após a administração SA do meloxicam, encorajando a realização de estudos adicionais com modelos de dor ou doses distintas. / Evidences show that both isoforms of cyclooxygenase (COX) are constitutively expressed in the spinal cord (SC) of rats; COX-2 is predominant in the spinal cord dorsal horn (SCDH) and capable of having an important role in the development and maintenance of inflammatory pain. Thus, it is suggested that non-steroidal antiinflammatory drugs (NSAIDs) may exercise their analgesic action directly on central nervous system (CNS), and spinal administration of these drugs has emerged as an alternative in pain management. This study aims therefore to assess the effects of subarachnoid administration (SA) of meloxicam in a model of inflammatory pain as well as its possible toxicity on the CNS. Twenty-seven Wistar male rats were used, in which a SA catheter was implanted. The animals were randomly distributed in three groups and submitted to administration of 5 L of saline (Group I-GI), 30 g of meloxicam (Group II-GII) or only to chronic maintenance of SA catheter (Group IIIGIII). The mechanical hypernociception was induced by intraplantar injection of carrageenan and assessed with the use of a digital analgesymeter during a period of four hours. To study the neurotoxicity, the animals were assessed daily for body weight, behavioral changes and neurological functions, being euthanized by transcardiac perfusion in one, seven or fourteen days after implantation of SA catheter. The SC was collected and submitted to histopathologic analysis. Results showed that the administration of meloxicam in the 30 g.animal-1 dose was not capable of suppressing hypernociceptive mechanical response induced by carrageenan. No animal, however, exhibited any changes in behavior or neurological functions during the observation period, neither difference in body weight variation among groups. Histopathologic analysis of SC did not show differences among the experimental groups, but revealed the presence of severe alterations related to the presence of SA catheter, especially in the cervical. These data suggest the absence of neurotoxic effects after SA administration of meloxicam, encouraging further studies in pain models or different doses.

L'appellation ‘desserts laitiers neutres' regroupe de nombreux produits de composition similaire mais de structure et de texture différente. Trois de leurs composants et leurs interactions définissent leur structure : l'amidon, les carraghénanes et les protéines de lait. L'objectif de cette thèse était de mieux appréhender les mécanismes physico-chimiques impliqués dans la mise en place de la structure de ces produits et leur impact sur la perception sensorielle.Ce travail s'est focalisé sur les interactions entre l'amidon et les carraghénanes en présence ou non de protéines de lait. De l'amidon modifié de maïs cireux, du lait écrémé reconstitué et des kappa-carraghénanes ont été utilisés. Différentes interactions ont été mises en avant par l'utilisation d'outils rhéologiques et microscopiques. En mélange binaire le carraghénane s'adsorbe sur le granule d'amidon gonflé. Cette interaction dépend de la densité de charge, et de la masse moléculaire du carraghénane utilisé. En mélange ternaire le carraghénane interagit préférentiellement avec les micelles de caséines et ce quel que soit le moment ou le lait est ajouté (avant ou après empesage de l'amidon). Cette modification de l'ordre d'incorporation des ingrédients permet d'obtenir des produits de microstructures différentes. Dans les deux cas les granules d'amidon sont inclus dans un réseau carraghénanes / micelles de caséines mais les caractéristiques de ces deux phases (amidon et carraghénanes / micelles de caséines), responsables de la structuration des produits, sont modifiées. Afin d'en évaluer l'impact sur la perception sensorielle de crèmes, neuf produits de formules identiques mais assemblés différemment ont été fabriqués. Un tri libre, suivi d'un classement des groupes sur des termes discriminants à consonance personnelle, ont été mis en place. Des différences entre les produits ont été perçues. Ces différences ont été décrites par des termes de texture corrélés à des mesures instrumentales de texture.Ce travail a permis de mettre en avant les mécanismes physico chimiques déterminants dans la mise en place de la structure ainsi que leur potentiel impact sur les propriétés sensorielles de produits de type crèmes desserts. Ces connaissances pourraient être mises à profit dans des démarches de conception raisonnée ou de rétro ingénierie pour formuler de nouveaux produits. / Neutral dairy desserts are composed of a large diversity of products of similar composition but different structures and textures. Their structure set up is defined by the interactions between three of their quantitatively minor components: starch, milk proteins and carrageenan. The objective of this PhD project was to better understand the chemical-physics mechanisms beyond the neutral dairy desserts structure set up and their impact on the sensory perception of the product.The study focused on single, binary and ternary mixtures containing starch. It was performed with a modified waxy maize starch, reconstituted skim milk and kappa carrageenan mostly. Using rheological and microscopic tools, different interactions were highlighted. In binary mixtures, carrageenan was found to adsorb on the starch granules. A specific study on those interactions pointed out that they depended on carrageenans' charge density and molecular weights. In ternary mixtures, preferential carrageenan / casein micelles interactions in comparison to starch / carrageenan ones were pointed out even when milk proteins were added after starch pasting in a carrageenan solution. The addition of milk before or after starch pasting led to products of same formula but different microstructures. Starch granules were in both cases embedded in a carrageenan / casein micelles network still, the starch granules states or characteristics and the network formed differed. Dispersed starch and carrageenan / milk phases were defined as the key structure parameters of neutral dairy desserts. To assess their impact on sensorial perception, nine products of same formula but built differently were produced. The evaluation was done by subjects by means of a free sorting task followed by a ranking task on free discriminating terms. Sensory differences were found between the products. These differences were characterized and correlated with instrumental attributes.This work permitted to collect numerous data on chemical-physics properties, link them to the structure set up and to their potential impact on sensory properties of dairy creams. All this knowledge would be easily used to improve tailor food development and particularly to formulate new dairy cream texture through a reverse engineering approach.

LIMA, Ticiana de Brito. Cultivo da alga marinha vermelha Solieria filiformis (Kützing) P.W. Gabrielson: textura de géis aquosos e lácteos. 2012. 71 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal do Ceará, Fortaleza-CE, 2012. / Submitted by Eric Santiago (erichhcl@gmail.com) on 2016-07-13T13:40:06Z No. of bitstreams: 1 2012_dis_tblima.pdf: 3568499 bytes, checksum: d48f3a061d05e6c3a9b0df95c1bf6115 (MD5) / Approved for entry into archive by José Jairo Viana de Sousa (jairo@ufc.br) on 2016-07-14T22:56:09Z (GMT) No. of bitstreams: 1 2012_dis_tblima.pdf: 3568499 bytes, checksum: d48f3a061d05e6c3a9b0df95c1bf6115 (MD5) / Made available in DSpace on 2016-07-14T22:56:09Z (GMT). No. of bitstreams: 1 2012_dis_tblima.pdf: 3568499 bytes, checksum: d48f3a061d05e6c3a9b0df95c1bf6115 (MD5) Previous issue date: 2012 / The red seaweed Solieria filiformis, abundant in Ceará, biossintetiza, among other polysaccharides, phycoloide called carrageenan of great commercial importance due to its properties thickeners, stabilizers and gelling agents. In Brazil, exotic species of marine algae are being grown on a commercial scale in order to meet the demand of industrial phycoloide. The aim of this study was to analyze the texture of aqueous gels made with milk and carrageenan extracted from seaweed S. filiformis, cultivated in Ceará through sporulation natural technique, in order to establish a comparison between these gels and those prepared with commercial carrageenans (iota and kappa carrageenan). The algae were grown through sporulation natural, where monthly PVC structures (25 mm) in size 25 x 44 cm, each containing a single nylon cord (10 mm) of 23 m length were kept at depths of 1 and 2 m over a period of nine months. For extraction of carrageenan were collected at both depths seaweed samples S. filiformis backstage with higher and lower biomass, some for the rainy season (January and April) and dry (October and November). Initially, the algae were dried, crushed in electric grinder and subjected to aqueous extraction (1.5% m / v), stirring every 20 minutes in a water bath at 90 °C for 4 h. The homogenates were filtered through nylon cloth, the waste discarded. The filtrates were subjected to filtration on a vacuum funnel sintered plate, and carrageenans obtained were frozen, lyophilized and weighed. The highest yields were obtained from carrageenan seaweed collected from the scenes that have accumulated during the dry spores (35.6% - November 2M to 45.3% - October 1M), while the algae that accumulated during the rainy season had the lowest incomes (29 6% - April 1M to 33.8% - April 2M). In contrast, levels of total sugars ranged between 37.6 and 50.5% and the content of carrageenan sulfate ranged from 21.6 to 33.3% according to the levels already checked to carrageenans of the iota type. The texture of aqueous gels in the presence of CaCl2 and 0.1% milk prepared with carrageenan S. filiformis and commercial concentrations of 0.5 and 1.5%, were analyzed for firmness, adhesiveness, cohesiveness, springiness, gumminess and chewiness. All samples with carrageenan derived from S. filiformis backstage obtained values of firmness, gumminess and chewiness than those found for ι-carrageenan commercial. Backstage November had the highest values in the parameter of firmness for aqueous gels and compared to ι-carrageenan commercial dairy. Adhesiveness, elasticity and cohesiveness showed values close to those found for ι-carrageenan commercial. The results for firmness and chewiness of κ-carrageenan were superior when compared to commercial car ι-carrageenan and S. filiformis. The gels formulated with milk obtained results strongly higher than those formulated with a solution of calcium chloride 0.1% due to interactions between the proteins and the milk carrageenan. With the data obtained it can be concluded that the use of carrageenan S. filiformis derived by sporulation natural cultivation is capable of forming gels when compared to stronger ι-carrageenan commercial could generate savings through the use of lower concentrations of the carrageenan commercial, to obtain the desired firmness of a product. / A alga marinha vermelha Solieria filiformis, abundante no litoral cearense, biossintetiza, dentre outros polissacarídeos, um ficocolóide denominado carragenana de grande importância comercial devido às suas propriedades espessantes, estabilizantes e gelificantes. No Brasil, espécies exóticas de algas marinhas vêm sendo cultivadas em escala comercial com o objetivo de suprir a demanda industrial desse ficocolóide. O objetivo desse trabalho foi analisar a textura de géis aquosos e lácteos elaborados com ι-carragenana extraída da alga S. filiformis, cultivada no litoral cearense através da técnica de esporulação natural, com a finalidade de estabelecer um comparativo entre esses géis e aqueles elaborados com carragenanas comerciais (ι e κ carragenanas). As algas foram cultivadas através de esporulação natural, onde mensalmente estruturas de PVC (25 mm) de tamanho 25 x 44 cm, contendo cada uma única corda de nylon (10 mm) de 23 m de comprimento foram mantidas em profundidades de 1 e 2 m durante um período de nove meses. Para extração da ι-carragenana foram coletadas em ambas profundidades amostras da alga S. filiformis dos bastidores que apresentaram maior e menor biomassa, determinadas para a estação chuvosa (Janeiro- 26,2 Kg e Abril- 46,5 Kg) e seca (Outubro- 53,0 Kg e Novembro- 31,7 Kg). Inicialmente, as algas foram secas, trituradas em moinho elétrico e submetidas à extração aquosa (1,5% m⁄v), sob agitação a cada 20 minutos, em banho-maria a 90 ºC durante 4 h. Os homogenatos foram filtrados em tecido de nylon, os resíduos descartados. Os filtrados foram submetidos a uma filtração à vácuo em funil de placa sinterizada, e as carragenanas obtidas foram congeladas, liofilizadas e pesadas. Os maiores rendimentos de ι-carragenana obtidos foram das algas coletadas dos bastidores que acumularam esporos no período seco (35,6%- Novembro 2M a 45,3%- Outubro 1M), enquanto as algas que acumularam no período chuvoso apresentaram os menores rendimentos (29,6%- Abril 1M a 33,8%- Abril 2M). Já os teores de açúcares totais variaram entre 37,6 e 50,5% e os teores de sulfato das carragenanas variaram de 21,6 a 33,3%, de acordo com os teores já verificados para carragenanas do tipo ι. A textura dos géis aquosos na presença de CaCl2 0,1% e lácteos preparados com as ι- caragenanas de S. filiformis e caragenanas comerciais nas concentrações de 0,5 e 1,5%, foram analisados quanto a firmeza, adesividade, coesividade, elasticidade, gomosidade e mastigabilidade. Todas as amostras com ι-carragenanas de S. filiformis dos bastidores obtiveram valores de firmeza, gomosidade e mastigabilidade superiores aos encontrados para ι-carragenana comercial. Os bastidores de novembro das amostras com ι-carragenanas de S. filiformis obtiveram os maiores valores no parâmetro de firmeza para os géis aquosos e lácteos quando comparados aos géis comerciais. Adesividade, elasticidade e coesividade mostraram valores próximos aos encontrados para ι-carragenana comercial. Os resultados obtidos para firmeza e mastigabilidade da κ-carragenana foram superiores quando comparados a ι-carragenana de S. filiformis e ι-carragenana comercial. Os géis formulados com leite reconstituído obtiveram resultados de firmeza superiores aos formulados com solução de cloreto de cálcio 0,1%, devido às interações entre as proteínas do leite e a ι-carragenana. Com os dados obtidos pode-se concluir que a utilização da ι-carragenana de S. filiformis oriunda de cultivo por esporulação natural é capaz de formar géis mais firmes quando comparada a ι- carragenana comercial, podendo gerar economia através da utilização de concentrações de carragenana inferiores a comercial, para se obter a firmeza desejada para um produto.

Evidências demonstram que ambas as isoformas da ciclooxigenase (COX) são constitutivamente expressas na medula espinhal (ME) de ratos, sendo COX-2 predominante no corno dorsal da medula espinhal (CDME) e podendo apresentar importante papel no desenvolvimento e manutenção da dor inflamatória. Assim, sugerese que os antiinflamatórios não-esteroidais (AINEs) possam exercer sua ação analgésica diretamente sobre o sistema nervoso central (SNC), e a administração espinhal desses fármacos tem despontado como uma alternativa no manejo da dor. O presente estudo objetiva, portanto, avaliar os efeitos da administração subaracnóidea (SA) do meloxicam em um modelo de dor inflamatória, bem como sua possível toxicidade sobre o SNC. Foram utilizados 27 ratos Wistar, machos, nos quais uma cânula SA foi implantada. Os animais foram aleatoriamente distribuídos em três grupos e submetidos à administração de 5 L de solução salina (Grupo I – GI), 30 g de meloxicam (Grupo II – GII) ou somente à manutenção crônica da cânula SA (Grupo III – GIII). A hipernocicepção mecânica foi induzida pela injeção intraplantar de carragenina e avaliada com o emprego de um analgesímetro digital durante um período de 4 horas. Para estudo da neurotoxicidade, os animais foram diariamente avaliados quanto ao peso corporal, alterações comportamentais e funções neurológicas, sendo mortos por perfusão transcardíaca um, sete ou 14 dias após a implantação da cânula SA. A ME foi coletada e submetida à análise histopatológica. Os resultados demonstraram que a administração do meloxicam na dose de 30 g.animal-1 não foi capaz de suprimir a resposta hipernociceptiva mecânica induzida pela carragenina. Nenhum animal, contudo, apresentou qualquer alteração comportamental ou das funções neurológicas durante o período de observação, tampouco ocorrendo diferença na variação do peso corporal entre os grupos. A análise histopatológica da ME não apresentou diferenças entre os grupos experimentais, entretanto revelou a presença de alterações severas relacionadas à presença da cânula SA, especialmente na região cervical. Estes dados sugerem a ausência de efeitos neurotóxicos após a administração SA do meloxicam, encorajando a realização de estudos adicionais com modelos de dor ou doses distintas. / Evidences show that both isoforms of cyclooxygenase (COX) are constitutively expressed in the spinal cord (SC) of rats; COX-2 is predominant in the spinal cord dorsal horn (SCDH) and capable of having an important role in the development and maintenance of inflammatory pain. Thus, it is suggested that non-steroidal antiinflammatory drugs (NSAIDs) may exercise their analgesic action directly on central nervous system (CNS), and spinal administration of these drugs has emerged as an alternative in pain management. This study aims therefore to assess the effects of subarachnoid administration (SA) of meloxicam in a model of inflammatory pain as well as its possible toxicity on the CNS. Twenty-seven Wistar male rats were used, in which a SA catheter was implanted. The animals were randomly distributed in three groups and submitted to administration of 5 L of saline (Group I-GI), 30 g of meloxicam (Group II-GII) or only to chronic maintenance of SA catheter (Group IIIGIII). The mechanical hypernociception was induced by intraplantar injection of carrageenan and assessed with the use of a digital analgesymeter during a period of four hours. To study the neurotoxicity, the animals were assessed daily for body weight, behavioral changes and neurological functions, being euthanized by transcardiac perfusion in one, seven or fourteen days after implantation of SA catheter. The SC was collected and submitted to histopathologic analysis. Results showed that the administration of meloxicam in the 30 g.animal-1 dose was not capable of suppressing hypernociceptive mechanical response induced by carrageenan. No animal, however, exhibited any changes in behavior or neurological functions during the observation period, neither difference in body weight variation among groups. Histopathologic analysis of SC did not show differences among the experimental groups, but revealed the presence of severe alterations related to the presence of SA catheter, especially in the cervical. These data suggest the absence of neurotoxic effects after SA administration of meloxicam, encouraging further studies in pain models or different doses.

Evidências demonstram que ambas as isoformas da ciclooxigenase (COX) são constitutivamente expressas na medula espinhal (ME) de ratos, sendo COX-2 predominante no corno dorsal da medula espinhal (CDME) e podendo apresentar importante papel no desenvolvimento e manutenção da dor inflamatória. Assim, sugerese que os antiinflamatórios não-esteroidais (AINEs) possam exercer sua ação analgésica diretamente sobre o sistema nervoso central (SNC), e a administração espinhal desses fármacos tem despontado como uma alternativa no manejo da dor. O presente estudo objetiva, portanto, avaliar os efeitos da administração subaracnóidea (SA) do meloxicam em um modelo de dor inflamatória, bem como sua possível toxicidade sobre o SNC. Foram utilizados 27 ratos Wistar, machos, nos quais uma cânula SA foi implantada. Os animais foram aleatoriamente distribuídos em três grupos e submetidos à administração de 5 L de solução salina (Grupo I – GI), 30 g de meloxicam (Grupo II – GII) ou somente à manutenção crônica da cânula SA (Grupo III – GIII). A hipernocicepção mecânica foi induzida pela injeção intraplantar de carragenina e avaliada com o emprego de um analgesímetro digital durante um período de 4 horas. Para estudo da neurotoxicidade, os animais foram diariamente avaliados quanto ao peso corporal, alterações comportamentais e funções neurológicas, sendo mortos por perfusão transcardíaca um, sete ou 14 dias após a implantação da cânula SA. A ME foi coletada e submetida à análise histopatológica. Os resultados demonstraram que a administração do meloxicam na dose de 30 g.animal-1 não foi capaz de suprimir a resposta hipernociceptiva mecânica induzida pela carragenina. Nenhum animal, contudo, apresentou qualquer alteração comportamental ou das funções neurológicas durante o período de observação, tampouco ocorrendo diferença na variação do peso corporal entre os grupos. A análise histopatológica da ME não apresentou diferenças entre os grupos experimentais, entretanto revelou a presença de alterações severas relacionadas à presença da cânula SA, especialmente na região cervical. Estes dados sugerem a ausência de efeitos neurotóxicos após a administração SA do meloxicam, encorajando a realização de estudos adicionais com modelos de dor ou doses distintas. / Evidences show that both isoforms of cyclooxygenase (COX) are constitutively expressed in the spinal cord (SC) of rats; COX-2 is predominant in the spinal cord dorsal horn (SCDH) and capable of having an important role in the development and maintenance of inflammatory pain. Thus, it is suggested that non-steroidal antiinflammatory drugs (NSAIDs) may exercise their analgesic action directly on central nervous system (CNS), and spinal administration of these drugs has emerged as an alternative in pain management. This study aims therefore to assess the effects of subarachnoid administration (SA) of meloxicam in a model of inflammatory pain as well as its possible toxicity on the CNS. Twenty-seven Wistar male rats were used, in which a SA catheter was implanted. The animals were randomly distributed in three groups and submitted to administration of 5 L of saline (Group I-GI), 30 g of meloxicam (Group II-GII) or only to chronic maintenance of SA catheter (Group IIIGIII). The mechanical hypernociception was induced by intraplantar injection of carrageenan and assessed with the use of a digital analgesymeter during a period of four hours. To study the neurotoxicity, the animals were assessed daily for body weight, behavioral changes and neurological functions, being euthanized by transcardiac perfusion in one, seven or fourteen days after implantation of SA catheter. The SC was collected and submitted to histopathologic analysis. Results showed that the administration of meloxicam in the 30 g.animal-1 dose was not capable of suppressing hypernociceptive mechanical response induced by carrageenan. No animal, however, exhibited any changes in behavior or neurological functions during the observation period, neither difference in body weight variation among groups. Histopathologic analysis of SC did not show differences among the experimental groups, but revealed the presence of severe alterations related to the presence of SA catheter, especially in the cervical. These data suggest the absence of neurotoxic effects after SA administration of meloxicam, encouraging further studies in pain models or different doses.

Temporomandibular Disorder (TMD) is a dysfunction that affects the temporomandibular joint (TMJ), characterized primarily by the presence of pain. It has been shown that low level laser therapy (LLLT) presents analgesic and anti-inflammatory effects in cases of TMD, but still experimental studies are scarce in order to understand the mechanisms involved in this biological activity. Therefore, the purpose of this work was to evaluate the ability of LLLT to control pain and inflammation induced by different chemical agents injected in the rat s TMJ. A study was carried out in two steps. At first induction of nociception was performed with 2.5% formalin in 25 Wistar rats ATM of 25 (300 ± 50 g), which they were randomly divided into 05 groups (n=5): CRG (no treatment); DFN (diclofenac sodium); LST1 (LLLT 12,5 J/cm2); LST2 (LLLT 52.5 J/cm2) and LST3 (LLLT 87.5 J/cm2). The LLLT was performed in a single application, with the apparatus laser with 780 nm (GaAlAs diode laser). The animals were evaluated considering the nociceptive behaviors characterized by rubbing the orofacial (RO) region and flinching the head (FH) quickly, analyzed separately and summed the behaviors. Data were analyzed through Anova test (one way) and Tukey s test. In the second stage, inflammation was induced in the TMJ of 45 Wistar rats (300 ± 50 g) with carrageenan to 1%. Then, the animals were divided into 03 main groups (n=15): CRG (no treatment); DFN (diclofenac sodium) and LST3 (LLLT 52.5 J/cm2). The LLLT was performed every 48 h, with the laser device described above. At specific times (24 h, 3 days and 7 days) five animals from each group were randomly sacrificed and their TMJ specimens were processed and stained with hematoxylin/eosyn (HE). The data were submitted to descriptive analysis regarding to semiquantitative and morphostrutural changes and mphasizing the inflammatory aspects and vascular neoformation. Data were analyzed through Kruskal-Wallis test and Dunn s post-hoc test. The results showed that DFN, LST2 and LST3 significantly reduced nociceptive responses characterized by the sum of the behaviors of FH and RO (p<0.001). DFN was also able to reduce the behaviors of FH (p< 0.05) and CO (p< 0.01) when assessed separately, as well as it was observed in LST2 (FH and RO, p<0.001). The LST1 did not elicit nociceptive effect. In the histological analysis, an inflammatory infiltration was observed significantly more intense in CRG than in DFN and LST2 in 24 h (P<0.05 e p<0.001), 3 days (p<0.01 e p<0.001) and 7 days (p<0.001 e p<0.01). In addition, the contingent of neutrophils was more conspicuous in CRG than in other groups in 24h. The vascular neoformation was less expressive in CRG than DFN (p<0.001) and LST2 (p<0.001) in 24 h, while in 3 days, exhibited greater quantitative LST2 blood vessels than CRG (p<0.001) and DFN (p<0.001). In 7 days, there was no difference in vascular content between experimental groups (p>0.05). Based on the results, one might conclude that the LLLT showed anti-inflammatory and antinociceptive effect in the inflammation induced in the TMJ of animals. / A Desordem temporomandibular (DTM) é uma disfunção que afeta a articulação temporomandibular (ATM), sendo caracterizada principalmente pela presença de dor. Tem sido demonstrado que fototerapia laser de baixa potência (FLBP) apresenta efeitos analgésicos e anti-inflamatórios em casos de DTM, mas ainda são escassos os estudos experimentais que permitam compreender os mecanismos envolvidos nesta atividade biológica. Sendo assim, o propósito desse trabalho foi avaliar a capacidade da FLBP em controlar a dor e a inflamação induzidas na ATM de ratos com diferentes agentes químicos. Para isso, foi realizado um estudo em duas etapas. Na primeira, foi induzida nocicepção com formalina a 2,5% na ATM de 25 ratos Wistar (325 ± 25 g), que foram então distribuídos aleatoriamente em 05 grupos (n=5): CRG (sem tratamento); DFN (tratados com diclofenaco sódico); LST1 (tratado com FLBP 12,5 J/cm2); LST2 (tratado com FLBP 52,5 J/cm2) e LST3 (tratado com FLBP 87,5 J/cm2). A FLBP foi realizada em única aplicação, com laser diodo GaAlAs a 780 nm. Os animais foram avaliados em relação aos comportamentos de levantar a cabeça (LC), coçar a face (CO), analisados separadamente e somados os comportamentos. Os dados foram analisados por meio de teste Anova (uma via) e teste de Tukey. Na segunda etapa, foi induzida inflamação na ATM de 45 ratos Wistar (325 ± 25 g) com carragenina a 1%. Posteriormente, os animais foram divididos em 03 grupos principais (n=15): CRG (sem tratamento), DFN (tratados com diclofenaco sódico) e LST2 (tratado com FLBP 52,5 J/cm2). A FLBP foi realizada a cada 48 h, com laser diodo GaAlAs a 780 nm. Em 24 h, 3 e 7 dias, cinco animais de cada grupo foram randomicamente eutanasiados e os espécimes de ATM foram processados e corados com hematoxilina/eosina (HE). Foi realizada análise descritiva das alterações morfoestruturais e semiquantitativa da intensidade da resposta inflamatória e neoformação vascular. Os dados foram analisados pelo teste Kruskal-Wallis e extensão posthoc de Dunn. Os resultados demonstraram que o DFN, o LST2 e o LST3 significativamente reduziram as respostas nociceptivas caracterizadas pela soma dos comportamentos de LC e CO (p<0.001). DFN também foi capaz de reduzir os comportamentos de LC (p<0.05) e CO (p<0.01) quando avaliados separadamente, da mesma forma que o LST2 (LC e CO, p<0.001). O LST1 não apresentou efeito antinociceptivo. Na análise histológica, foi observada uma infiltração inflamatória significativamente mais intensa in CRG do que em DFN e LST2 em 24 h (P<0,05 e p<0,001), 3 dias (p<0,01 e p<0,001) e 7 dias (p<0,001 e p<0,01). Além disso, o contingente de neutrófilos foi mais conspícuo em CRG do que nos demais grupos em 24 h. A neoformação vascular se apresentou menos expressiva em CRG do que DFN (p<0,001) e LST2 (p<0,001) em 24 h, enquanto que em 3 dias, LST2 exibiu maior quantitativo de vasos sanguíneos que CRG (p<0,001) e DFN (p<0,001). Em 7 dias, não houve diferença no conteúdo vascular entre os grupos (p>0,05). Baseado nos resultado pôde-se concluir que a FLBP apresentou atividade antinociceptiva e anti-inflamatória na indução realizada na ATM de animais experimentais.