Phytochemical investigation on Vitex negundo leaves and their anti-inflammatory and analgesic activities

Abstract The phytochemical investigation on Vitex negundo leaves has led to the isolation of one new iridoid glucoside (8α-hydroxy-4-carboxyl-5ßH-9ßH-iridoid-1α-O-(6'-O-(6,7-dihydrofoliamenthonyl)-ß-ᴅ-glucopyranoside, 3), together with three known compounds, namely agnuside (1), 6'-O-E-caffeoylmussaenosidic acid (2), and 3,5-dicaffeoylquinic acid (4). The HPLC analytical study was also performed to quantify the content of agnuside (1) in dried leaves. The results indicated the very high content of 1 (3.04 ± 0.02%). The method was also validated by various parameters, including linearity (R2= 0.9999), precision (intra-day RSD ≤ 2.50%, inter-day RSD= 0.76%), and accuracy (recovery rates 96.58-101.86%). The animal testing data showed that the extract did not reduce pain at the doses of 9.6 and 28.8 g /kg (leaf weight/body weight) in the hot plates and pain measuring models but showed the pain reduction in the acetic acid-induced pain model. The extract at the dose of 5.6 g/kg (leaf weight/body weight) also had effects on the acute inflammation in the carrageenin-induced edema model. The extract at the dose 9.6 and 28.8 g/kg (leaf weight/body weight) also showed significant chronic anti-inflammation, comparable to methylprednisolone at the dose 10 mg/kg on the mouse peritoneal

Analgesic, antipyretic, anti-inflammatory, and hepatoprotective activities of Pulicaria crispa (Forssk. ) Oliv. (Asteraceae)

Abstract Some plants of the genus Pulicaria have been used in traditional medicines for treating back pain and inflammation. They possess various bioactivities such as antipyretic, analgesic, and hepatoprotective. This study aimed to investigate the potential analgesic, antipyretic, anti- inflammatory, and hepatoprotective activities of Pulicaria crispa (P. crispa) extract (PCE). Analgesic activity was evaluated using the hot plate and acetic acid-induced writhing tests. Antipyretic and anti-inflammatory activities were evaluated using rectal temperature and carrageenan-induced hind paw edema methods, respectively. CCl4-intoxication was used for hepatoprotective activity. Also, liver histopathology was assessed. PCE, at 500 mg/kg, exhibited significant analgesic, antipyretic, and anti-inflammatory effects. The increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin of CCl4-exposed rats reflects their liver injury. PCE significantly decreased the elevated liver markers. The hepatoprotective effect of PCE was confirmed, as it successfully reversed the altered levels of total protein, malondialdehyde (MDA), and non-protein sulfhydryls (NP-SH) in the liver tissues of CCl4-exposed rats. Histopathological studies confirmed the hepatoprotective nature of PCE. Pretreatment of rats with PCE reduced the severity of CCl4-induced liver damage. These findings concluded that PCE possesses analgesic, antipyretic, anti-inflammatory, and hepatoprotective activities.

Manejo de analgésicos en ortodoncia / Analgesic management in orthodontics

Antecedentes: El dolor y el miedo al dolor durante el tratamiento odontológico son frecuentes tanto en la práctica general como en la especialidad de la ortodoncia. El dolor de variada intensidad se presenta en 94% de los pacientes durante el primer día del tratamiento ortodóncico y todavía al sexto día lo padece aproximadamente 50%. Sin embargo, en muchas ocasiones los pacientes no reciben una receta médica o medicamentos para el alivio del dolor y esto puede conducir a la automedicación. Objetivos: El propósito de este estudio fue determinar el manejo del dolor que el ortodoncista realiza durante el tratamiento dental. Material y métodos: Este estudio es de tipo transversal mediante una encuesta de respuesta inmediata a 51 odontólogos especialistas en ortodoncia egresados de diferentes universidades y en diferentes tiempos. Asimismo, fueron entrevistados 100 pacientes ortodóncicos portadores de brackets a quienes se les realizaron preguntas relacionadas con la percepción de dolor y el manejo farmacológico de éste durante la cementación de brackets, cambio del arco de alambre o activación de sus aparatos. Resultados: 35.3% (n = 18/51) de los ortodoncistas prescriben analgésicos de manera habitual, mientras que 64.7% (n = 33/51) no lo hacen y 29.4% (n = 15/51) los indican con horario fijo. El analgésico de elección fue el paracetamol (64.7%; n = 33/51). 51% (n = 26/51) de los ortodoncistas refieren que no emplean analgésicos porque no existe dolor durante el tratamiento dental, o si lo hay, es leve, transitorio y tolerable. 52% (n = 52/100) recibió la instrucción verbal de tomar analgésicos en caso de ser necesario, mientras que al resto no se le dio tal indicación. Del total de pacientes sólo 4% (n = 4/100) no percibió dolor durante el tratamiento, en tanto que el resto presentó dolor leve (19%), moderado (57%) y severo (20%). La frecuencia de días con dolor posterior a la cementación o activación de los brackets fue de 1-3 días (56%). El principal trastorno ocasionado por el tratamiento fue la alteración de la masticación, es decir, la incapacidad y/o dolor durante la masticación se presentó en 86%, y 42% se adaptó a la presencia de los brackets en su boca en un tiempo de entre dos a cuatro semanas. Conclusiones: La mayoría de los ortodoncistas encuestados afirman que el dolor producido por las fuerzas ortodóncicas es de baja intensidad y el paciente lo tolera muy bien, por lo que la administración de analgésicos es innecesaria y cuando tienen que recetar algún medicamento, el de su preferencia es el paracetamol; sin embargo, no lo recetan con dosis y horario fijo. La afirmación de parte de 51% de los ortodoncistas respecto a que el paciente no presenta dolor durante el tratamiento ortodóncico no se cumple, ya que se encontró que 77% de los pacientes presentaron dolor entre moderado y severo durante al menos 1-3 días posteriores a la cementación o activación de los aparatos (AU)

Background: Pain and fear of suffering during the orthodontic treatment, are still frequent in both general and specialty dental practice, including the orthodontics. The pain with different intensity, it is shown in the 94% of the patient, during the 1st day of the orthodontic treatment but still, during the 6th day, it appears to the 50% of the patients. Nevertheless, on many occasions, the patients do not receive any prescription or pain relief medication and this may lead to self-medication. Objectives: The purpose of this study was to determine the pain management that the orthodontist performs during dental treatment. Material and methods: This cross-sectional study was carried out by an immediate response survey to 51 orthodontic dentists graduated from different universities and at different times. We also interviewed 100 orthodontic patients who were asked questions related to their perception of pain and its pharmacological management during the activation of the devices. Results: 35.3% (n = 18/51) of orthodontists usually prescribe analgesics while the 64.7% (n = 33/51) they won't give any prescriptions; 29.4% (n = 15/51) indicating a specific time. The analgesic choice was paracetamol (64.7%; n = 33/51). 51% (n = 26/51) of the orthodontist they said that most of the time they won't give any prescription because there was no pain during the dental treatment, or in case that exists, they comment that is transitory or is a tolerated pain. The 52% (n = 52/100) they received the indication of taking analgesics in case they needed it, whereas the rest weren't receiving any indication. Of all patients only 4% (n = 4/100) did not feel pain during their treatment; meanwhile, the 19% felt a mild pain; 57% felt a moderate pain and 20% severe pain. The frequency with pain after the cementation or activation of the devices it is about 1 to 3 days (56%). The main disorder by the treatment was the chewing alteration (86%), and the 42% adapted to their braces in a time of 2-4 weeks. Conclusions: The majority of orthodontists enrolled, they had commented that the pain produced by the force of the braces is a low intensity and that the patient will tolerate without any problem, and because of that, there isn't a need to give them any prescription, and when there's a need the one of their preference is paracetamol, nevertheless they don't give the prescription with time and required doses. The affirmation from the 51% of the orthodontist about the patient that does not suffer any pain during their orthodontic treatment it's not according to the 77% who felt pain between moderate and severe during at least 1-3 days after the cementation or activation of devices (AU)

Synthesis of some novel pyrimidine, thiophene, coumarin, pyridine and pyrrole derivatives and their biological evaluation as analgesic, antipyretic and anti-inflammatory agents

Pyrimidine derivative 3 was afforded through the reaction of compound (1) with 5-ureidohydantion (2). Product 3 underwent a cyclization to produce fused pyrimidine derivative 7, although the latter product 7 was synthesized through one step via the reaction of compound (1) with 5-ureidohydantion (2) using another catalyst. Compound 3 was oriented to react with cyclic ketones 8a,b in the presence of elemental sulfur, salicylaldehyde (10), aryldiazonium chlorides 12a,b and ω-bromo-4-methoxy- acetophenone (14), which afforded, fused thiophene derivatives 9a,b, coumarin derivative 11, arylhdrazono derivatives 13a,b and 4-methoxyphenyl butenyl derivative 15, respectively. The latter product 15 was reacted with either potassium cyanide (16a) or potassium thiocyanide (16b) to form cyano and thiocyano derivatives 17a,b, respectively. Compound 17a underwent further cyclization to afford pyridopyrimidine derivative 19. Compound 15 was reacted with either hydrazine (20a) or phenylhydrazine (20b) to produce hydrazo derivatives 21a,b and these products were cyclize to produce pyrrole derivatives 23a,b. Finally, 5-ureidohydantion (2) was reacted with compounds 24a,b,c to afford pyrimidine derivatives 25a,b,c. The structures of the synthesized compounds were confirmed using IR, 1H NMR, 13C NMR and mass spectrometry techniques. Compounds 11 and 19 have promising as analgesic and antipyretic activities

Analgesia for patients undergoing shockwave lithotripsy for urinary stones – a systematic review and meta-analysis

ABSTRACT Background Shock wave lithotripsy (SWL) is the first line treatment modality for a significant proportion of patients with upper urinary tracts stones. Simple analgesics, opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are all suitable agents but the relative efficacy and tolerability of these agents is uncertain. Objectives To determine the efficacy of the different types of analgesics used for the control of pain during SWL for urinary stones. Materials and Methods We searched the Cochrane Renal Group’s Specialised Register, MEDLINE, EMBASE and also hand-searched reference lists of relevant articles (Figure-1). Randomised controlled trials (RCT’s) comparing the use of any opioid, simple analgesic or NSAID during SWL were included. These were compared with themselves, each-other or placebo. We included any route or form of administration (bolus, PCA). We excluded agents that were used for their sedative qualities. Data were extracted and assessed for quality independently by three reviewers. Meta-analyses have been performed where possible. When not possible, descriptive analyses of variables were performed. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals. Results Overall, we included 9 RCTs (539 participants from 6 countries). Trial agents included 7 types of NSAIDs, 1 simple analgesic and 4 types of opioids. There were no significant differences in clinical efficacy or tolerability between a simple analgesic (paracetamol) and an NSAID (lornoxicam). When comparing the same simple analgesic with an opioid (tramadol), both agents provided safe and effective analgesia for the purpose of SWL with no significant differences. There were no significant differences in pain scores between NSAIDs or opioids in three studies. Adequate analgesia could be achieved more often for opioids than for NSAIDs (RR 0.358; 95% CI 043 to 0.77, P=0.0002) but consumed doses of rescue analgesia were similar between NSAIDs and opioids in two studies (P=0.58, >0.05). In terms of tolerability, there is no difference in post-operative nausea and vomiting (PONV) between the groups (RR 0.72, 95% CI 0.24 to 2.17, P=0.55). One study compared outcomes between two types of NSAIDs (diclofenac versus dexketoprofen). There were no significant differences in any of our pre-defined outcomes measures. Conclusion Simple analgesics, NSAIDs and opioids can all reduce the pain associated with shock wave lithotripsy to a level where the procedure is tolerated. Whilst there are no compelling differences in safety or efficacy of simple analgesics and NSAIDs, analgesia is described as adequate more often for opioids than NSAIDs.

Curcumina, una alternativa térapéutica para la clínica dental. Parte: antiinflamatorio y analgésico / Curcumin, a therapeutic alternative for the dental clinic (Part I):An anti-inflammatory and analgesic

La curcumina es una sustancia derivada de una planta llamada Curcuma longa. A esta sustancia se le han atribuido diversos efectos terapéuticos. En relación con la clínica dental, se ha observado que, además de ayudaren el control del dolor, ha sido efectiva contra la periodontitis, estomatitis y mucositis pediátrica. El control del dolor e inflamación son aspectos muy importantes para la mayoría de los tratamientos en odontología; la búsqueda de nuevas alternativas analgésicas y antiinflamatorias que, en comparación con las actuales, sean más eficientes, efectivas y tengan menos efectos colaterales es uno de los grandes retos de las ciencias biomédicas. La presente revisión muestra algunas evidencias científicas de los efectos de la curcumina como un antiinflamatorio y analgésico, con el propósito de sentar las bases para futuros estudios clínicos y de ciencia básica que aporten un mayor entendimiento de los procesos celulares, bioquímicos, moleculares, fisiológicos y farmacológicos de la curcumina como una sustancia potencialmente útilen el consultorio dental.

Curcumin is a substance derived from the plant Curcuma longa andone that has been attributed a range of therapeutic eff ects. In dentalpractice, curcumin has not only been found to help with pain control, buthas also been eff ective against periodontitis, stomatitis, and pediatricmucositis. Controlling pain and infl ammation are both very importantaspects of most dental treatments. The search for more effi cient andeff ective analgesic and anti-infl ammatory alternatives with fewerside eff ects compared to those currently used is one of the greatestchallenges for biomedical science. This review presents some of thescientifi c evidence of the eff ects of curcumin, both as an analgesic andan anti-infl ammatory agent, in order to establish the foundations forfurther clinical and basic science studies that will provide a greaterunderstanding of the cellular, biochemical, molecular, physiological,and pharmacological processes of curcumin as a potentially usefulsubstance in dental practice.

The anti-inflammatory and antinociceptive effects of proteins extracted from Acacia farnesiana seeds / Efeito antiiflamatório e antinociceptivo de proteínas extraídas de sementes de Acacia farnesiana

ABSTRACT Seeds of Acacia farnesiana are commonly sold in the local markets of northeastern Brazil as a therapeutic agent. The present work aimed to evaluate the anti-inflammatory and analgesic activities of proteins obtained from A. farnesiana seeds. Five different protein fractions (albumin, globulin, prolamin, acidic and basic glutelins) were obtained and investigated for the protein pattern, the presence of hemagglutinating and proteolytic activities. The globulin fraction (GLB) was also evaluated for anti-inflammatory and analgesic activities. Globulins reduced the paw edema induced by carrageenan in a dose-dependent manner, which was accompanied by a reduction of myeloperoxidase activity (p < 0.05). Additionally, GLB reduced the neutrophil peritoneal migration induced by carrageenan. However, GLB was not able to inhibit the edema triggered by dextran. Pre-treatment with globulins reduced the abdominal constrictions induced by acetic acid as well as the paw licking time induced by formalin (69.1% at first phase). However, it did not produce a significant antinociceptive effect in the hot plate test (55-56 °C). Treating the GLB with heat (at 100 °C for 30 min) abolished its anti-edematogenic and hemagglutinating activities. Our results showed that seeds from A. farnesiana are a source of proteins with anti-inflammatory and analgesic properties.

RESUMO Sementes de Acacia farnesiana são comumente vendidas em feiras locais no nordeste do Brasil como agente terapêutico. O presente trabalho objetivou avaliar as atividades antiinflamatória e antinociceptiva de proteínas obtidas de sementes de A. farnesiana. Cinco frações protéicas distintas (albuminas, globulinas, prolaminas, glutelinas ácidas e básicas) foram obtidas e investigadas quanto o perfil de proteínas, presença de atividade hemaglutinante e proteolítica. A fração globulina (GLB) também foi avaliada quanto a presença de atividade antiinflamatória e analgésica. Globulinas reduziram o edema de pata induzido por carragenina de modo dependente da dose que foi acompanhada da redução da atividade da mieloperoxidase (p < 0,05). Em adição, GLB reduziu a migração de neutrófilos para cavidade peritoneal induzida por carragenina. Entretanto, GLB não foi capaz de inibir o edema induzido por dextrana. O pré-tratamento com globulinas reduziu as contorções abdominais induzidas por ácido acético, bem como o tempo de lambedura da pata induzida por formalina (69.1% na primeira fase). Por outro lado, GLB não produziu um efeito antinociceptivo significante no teste de placa quente (55-56 °C). O pré-tratamento de GLB com calor (100 °C por 30 min) aboliu sua atividade anti-edematogênica e hemaglutinante. Nossos resultados mostraram que sementes de A. farnesiana são fonte de proteínas com propriedades antiinflamatórias e analgésicas.

Atividade Antinociceptiva e Antimicrobiana da Casca do Caule de Psidium Cattleyanum Sabine / Antiniciceptive and antimicrobial activity of the stem bark of Psidium cattleyanum Sabine

RESUMO Psidium cattleyanum Sabine, conhecida como “araçá”, é espécie nativa do Bioma Cerrado brasileiro comumente utilizado, segundo levantamento etnobotânico, como planta medicinal para tratar várias doenças tais como: patologias hepáticas, gástricas, lesões teciduais incluindo processos dolorosos. O objetivo deste trabalho foi realizar a triagem fitoquímica com propósito exploratório, investigar a atividade analgésica e antimicrobiana do extrato hidroalcoólico da casca do caule de Psidium cattleyanum Sabine (ECPCS) para apoiar o uso dessa espécie como planta medicinal. Para isso, foram obtidos extratos e frações com solventes orgânicos de polaridade crescente (hexano, diclorometano, acetato de etila e isobutanol) avaliando-se o perfil fitoquímico para determinar as principais classes de metabólitos secundários presentes na espécie. Investigou-se a atividade analgésica pelo teste de contorções abdominais em camundongos induzidas pelo ácido acético (0,6%). A Concentração Inibitória Mínina (CIM) e Concentração Bactericida Mínima (CBM) foram avaliadas através da técnica de microdiluição em caldo contra micro-organismos da microbiota oral. A triagem fitoquímica identificou a presença de taninos, saponinas, flavonoides e terpenos e/ou esteroides. O ECPCS exibiu atividade analgésica periférica nas doses de 200 e 400 mg/kg. O EAC (extrato acetato de casca) o EDC (extrato diclorometânico de casca) desempenharam melhor ação inibitória sobre o crescimento bacteriano de Estafilococos oralis com CIM 100 e 150 respectivamente. O ECPCS desempenhou ação inibitória sobre o crescimento bacteriano. Os resultados dos estudos experimentais comprovaram a presença de compostos secundários tais como, taninos e flavonoides, o que, provavelmente, pode ser associado à atividade analgésica e ao efeito inibitório sobre os micro-organismos testados com o ECPCS, o que justifica o uso medicinal planta.

ABSTRACT The Psidium cattleyanum Sabine, known as “araçá”, is a native species from the Brazilian Cerrado biome, commonly used, according to ethnobotanical surveis, as a medicinal plant to treat several sicknesses such as liver and , gastric diseases and tissue lesions with painful treatments. The aim of this study was to perform an exploratory screening, investigating the analgesic and antimicrobial activity of the hydroalcoholic extract of the Psidium cattleyanum Sabine (BEPCS) stem bark, in order to support the use of this species as a medicinal plant. For that, the BEPCS and its parts were obtained from the extraction with organic solvents of increasing polarity (hexane, dichloromethane, ethyl acetate and isobutanol), evaluating its phytochemical profile in order to determine the main types of secondary metabolites present in the species. The analgesic activity, through the twisting test in mice, was investigated and induced by acetic acid (0.6%). The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were evaluated using the microdilution technique in liquid against microorganisms of the oral microbiota. The phytochemical screening identified the presence of tannins, saponins, flavonoids and terpenes and/or steroids. The BEPCS exhibited peripheral analgesic activity at the doses of 200 and 400 mg / kg. The AEB (acetate extract bark) and the DEB (dicloromethane extract bark) had better inhibitory effect on bacterial growth of Staphylococcus oraliswith MIC 100 and 150 respectively. The BEPCS demonstrated an inhibitory effect on bacterial growth. The results of experimental studies have indicated the presence of secondary compounds as tannins and flavonoids, which probably can be associated with the analgesic activity and inhibitory effect on the microorganisms tested with BEPCS, fact that justifies the its application.

Efeito analgésico e anti-inflamatório do extrato aquoso das folhas de trevo-roxo (Scutellaria agrestis A. St. -Hil. ex Benth. - Lamiaceae) em roedores / Analgesic and anti-inflammatory effect of the aqueous extract of "trevo-roxo" (Scutellaria agrestis A. St. -Hil. ex Benth. - Lamiaceae) leaves in rodents

Scutellaria agrestis é utilizada por comunidades ribeirinhas do Amazonas principalmente para o tratamento de otites por via tópica utilizando-se o extrato bruto obtido por maceração. O presente trabalho visou investigar preliminarmente o perfil fitoquímico, a segurança toxicológica e as ações analgésica, anti-inflamatória e antiedematogência do extrato aquoso das folhas de S. agrestis. Foram coletados 80 indivíduos da espécie no horto medicinal da Universidade Nilton Lins, Manaus, Brasil. O perfil fitoquímico foi obtido por meio de prospecção da droga vegetal para heterosídeos cianogênicos, terpenos, compostos fenólicos e alcaloides. A toxicologia foi avaliada pelo teste de toxicidade aguda. As atividades analgésicas/ anti-inflamatórias foram analisadas por meio dos testes de formalina em camundongos e a atividade antiedematogência, pelo teste de edema de pata em ratos. Os metabólitos detectados foram fenóis (taninos hidrolisáveis, cumarinas e várias classes de flavonoides) e terpenos (esteroides livres, saponinas). Não foi possível estabelecer DL50, haja visto que o extrato não provocou a morte de nenhum animal durante o teste de toxicidade aguda, provavelmente devido à ausência de heterosídeos cianogênicos na sua composição. Apesar de não provocar morte, considerou-se que o extrato apresenta uma discreta toxicidade, uma vez que foi observada a ocorrência de espasmos na primeira hora de observação dos animais. O extrato apresentou ainda efeito analgésico e anti-inflamatório significativo nas doses de 30, 100 e 300 mg/kg pelo teste da formalina, sendo o resultado na maior dose equivalente ao obtido com a droga padrão (fentanil). No entanto, não observamos efeito antiedematogênico nas doses testadas durante as 5 horas de registro do edema de pata. Os resultados obtidos nesta pesquisa conferem base científica preliminar quanto à segurança e ao efeito analgésico e antiinflamatório da droga vegetal, o que indica que tal espécie é promissora e expressamente recomendada para maiores estudos farmacológicos in vitro e in vivo.

The Scutellaria agrestis is used by Amazonas riverine communities, especially for otitis externa topical treatment, by using the crude extract obtained by maceration. This study aimed to investigate the preliminary phytochemical profile, the safety/toxicity and the analgesic, anti-inflammatory and antiedematogenic activities of the aqueous extract of the S. agrestis leaves. Eighty individuals were collected at the Nilton Lins University medicinal garden, Manaus, Brazil. The phytochemical profile was obtained through a plant drug survey for cyanogenic heterosides, terpenes, alkaloids and phenolic compounds. The extract safety was evaluated by acute toxicity test. Analgesic and anti-inflammatory activities were accessed using formalin test in mice and the antiedematogenic activity, using paw edema test in mice. We detected phenolic (hydrolysable tannins, coumarins and several classes of flavonoids) and terpenoid (free steroids, saponins) metabolites. We could not establish LD50 because no animals died during the acute toxicity test, probably because of the absence of cyanogenic glycosides on the composition of the extract. However, we found that the extract is slightly toxic as animal spasms were observed in the first hour of the test. The extract showed significant analgesic and anti-inflammatory activity on the formalin test (30, 100 and 300 mg/kg p.o.), and the highest dose result was equivalent to the standard drug (Fentanyl). However, no significant antiedematogenic effect was observed during the paw edema test. The results obtained in this study provide preliminary scientific basis about the safety and analgesic/anti-inflammatory actions of the aqueous extract of S. agrestis, which indicates that this species is a promising option for further in vitro and in vivo pharmacological studies.

Anti-inflammatory, analgesic, and immunostimulatory effects of Luehea divaricata Mart. & Zucc. (Malvaceae) bark

Luehea divaricata (Malvaceae) is a plant widely used for treatment of various inflammatory and infectious conditions; however few reports discuss its biological properties. The aim of this study was to evaluate the anti-inflammatory and analgesic effects as well as the macrophage activity in mice treated with the hydroalcoholic crude extract of L. divaricata (CLD). Thin layer chromatography revealed presence of epicathequin, stigmasterol, lupeol and α,β-amyrin in the extract. To evaluate the anti-inflammatory and analgesic activities, animals were subjected to paw edema induced by carrageenan test, writhing, formalin and capsaicin tests. Immunomodulatory activity was evaluated by adhesion and phagocytic capacity, lysosomal volume, and reactive oxygen species (ROS) production by peritoneal macrophages, after daily treatment with CLD for 15 days. CLD promoted reduction in paw edema (36.8% and 50.2%; p<0.05 at doses of 100 and 300 mg/kg, respectively), inhibited writhing behavior at the higher dose (64.4%, p<0.05), reduced formalin reactivity (81.2% and 91.6% at doses of 100 and 300 mg/kg, respectively, p<0.05), and reduced capsaicin reactivity by 63.9% (300 mg/kg). CLD (200 mg• kg-1• day-1) increased phagocytosis capacity of macrophages (~3 fold, p<0.05), neutral red uptake (~50%, p<0.001), and ROS production (~90%, p<0.001). These data suggest that CLD possesses anti-inflammatory, analgesic and immunostimulatory properties.

Luehea divaricata (Malvaceae) é utilizada para o tratamento de várias condições patológicas, entretanto, há poucos relatos sobre sua bioatividade. O objetivo deste estudo foi avaliar o efeito anti-inflamatório e analgésico, bem como a atividade de macrófagos em camundongos tratados com extrato bruto hidroalcoólico (CLD) da planta. Cromatografia em camada delgada revelou a presença de epicatequina, estigmasterol, lupeol e α,β-amirina no material. Para avaliar a atividade anti-inflamatória e analgésica, animais foram submetidos a teste de edema de pata induzido por carragenana, teste de contorções, da formalina e da capsaicina. A atividade imunomodulatória foi avaliada pela capacidade de adesão e de fagocitose dos macrófagos, volume lisossômico e produção de espécies reativas de oxigênio (ROS), após tratamento diário com CLD por 15 dias. CLD promoveu redução do edema de pata (36,8% e 50,2%; 100 e 300 mg/kg, respectivamente; p<0,05), redução do número de contorções (64,4%; 300 mg/kg; p<0,05), redução da reatividade no teste da formalina (81,2% e 91,6%; 100 e 300 mg/kg, respectivamente; p<0,05), e no teste da capsaicina em 63,9% (300 mg/kg). CLD (200 mg• kg-1• day-1) aumentou capacidade de fagocitose dos macrófagos (~3 vezes, p<0,05), volume lisossômico (~50%, p<0,001) e produção de ROS (~90%, p<0,001). Estes dados sugerem que o CLD possui propriedades anti-inflamatórias, analgésicas e imunoestimulatórias.

Anti-inflammatory and antinociceptive activities of methanolic extract from red seaweed Dichotomaria obtusata

The aim of the present work was to investigate the anti-inflammatory and antinociceptive effects of methanolic extract from D. obtusata using classic models in mice (croton oil-induced ear edema and acetic acid-induced writhing) and a phospholipase A2 activity test. Qualitative analysis of the chemical composition of seaweed was also determined by extraction with solvents of increasing polarity and precipitation and color tests. Results of qualitative chemical study showed the presence of lactonic and phenolic compounds, reduced carbohydrates, other sugars, flavonoids, fatty compounds, triterpenes and steroids. The extract inhibited mouse ear edema in a dose-dependent manner with an efficacy higher than 90% and a mean effective dose of 4.87µg/ear, while intraperitoneal administration presented a moderate activity. The extract did not inhibit phospholipase A2 activity. In the writhing test, the intraperitoneal administration of the extract showed a strong antinociceptive activity (80.2%), while the oral route showed a lower efficacy. In conclusion, this study demonstrated the anti-inflammatory and antinociceptive effects of methanol extract of D. obtusata in experimental models, suggesting its therapeutic potential in the treatment of peripheral painful and/or inflammatory pathologies.

O objetivo do presente trabalho foi investigar os efeitos antiinflamatórios e antinociceptivos de um extrato metanólico de D. obtusata, utilizando modelos clássicos em ratos (teste do edema de orelha induzido por óleo de cróton e teste de contorções induzidas por ácido acético) e um teste de atividade de fosfolipase A2. A análise qualitativa da composição química das algas foi também determinada através de extração com solventes de polaridade crescente e testes de precipitação e cor. Os resultados do estudo de química qualitativa mostraram a presença de compostos lactônicos e fenólicos, hidratos de carbono reduzidos e outros açúcares, flavonoides, compostos graxos, triterpenos e esteroides. O extrato inibiu o edema de orelha dos ratos de um modo dependente da dose com eficácia superior a 90% e dose média efetiva de 4.87µg/orelha, enquanto a administração intraperitoneal apresentou atividade moderada. O extrato não inibiu a atividade da fosfolipase A2. No teste de contorção, a administração intraperitoneal do extrato mostrou forte atividade antinociceptiva (80,2%), enquanto a administração oral mostrou menor eficácia. Em conclusão, este estudo demonstrou os efeitos antiinflamatórios e antinociceptivos do extrato metanólico de D. obtusata em modelos experimentais, sugerindo seu potencial terapêutico no tratamento de patologias dolorosas periféricas e/ou inflamatórias.

Analgesic and anti-inflammatory activities of several 4-substituted-6-(3'-nitrophenyl)pyridazin-(2H)-3-one derivatives

Several 6-aryl-4-substituted benzylidene/furfurylidene pyridazin(2H)-3-one derivatives (4a-f) were synthesized and evaluated as analgesic and anti-inflammatory agents in mice and rats, respectively. All compounds were tested by using Eddy's hot plate and the carrageenan-induced hind paw oedema method for the evaluation of analgesic and anti-inflammatory activities, respectively. Results showed that compounds 4f, 4b, 4d, and 4e exhibited higher analgesic and anti-inflammatory activities than other remaining compounds. All title compounds (4a-f) were characterized by IR, NMR and Mass spectroscopy.

Diversos derivados benzilideno/furfurilideno piridazin(2H)-3-ona 6-aril-4-substituídos (4a-f) foram sintetizados e avaliados como analgésicos e anti-inflamatórios em camundongos e ratos, respectivamente. Todos os compostos foram testados utilizando-se o método de placa quente de Eddy e o de edema de pata induzido por carragenana para a avaliação das atividades analgésica e anti-inflamatória, respectivamente. Os resultados mostraram que os compostos 4f, 4b, 4d e 4e exibiram atividade analgésica e anti-inflamatória mais alta do que os compostos restantes. Todos os compostos (4a-f) foram caracterizados por IV, RMN e espectrometria de massas.

Parámetros de práctica para el manejo del dolor en cáncer: Grupo de Consenso para el Manejo del Dolor en Cáncer / Practice guidelines for cancer pain management: Task Force for Cancer Pain Management

El dolor por cáncer es un problema frecuente en nuestro medio, se presenta en 80 a 90 % de los pacientes y en aproximadamente 90 % de ellos se resuelve con medidas relativamente sencillas. No obstante, aproximadamente 40 % de los pacientes se encuentra insatisfecho con el médico o la enfermera respecto al manejo de su dolor. Por tal motivo, se convocó a un grupo de consenso con la finalidad de generar parámetros de práctica clínica fundamentados en la evidencia publicada y en la opinión de los expertos. Este grupo estuvo integrado por 31 médicos líderes de opinión es este campo, quienes con base en 599 documentos emitieron esta serie de recomendaciones, identificadas cada una según su nivel de evidencia.

Cancer pain is a frequent medical problem in our society. This syndrome affects from 80 to 90% of cancer patients and can be solved with relatively simple measures in 90% of the cases. Approximately 40% of cancer patients reported to be unsatisfied with the physician or nurse about their pain management. For these reasons, we gathered a task force in order to generate practice guidelines based on medical evidence and on the opinion of experts in this area. These guidelines were generated by a task force of 31 physicians who were leaders in this field and based on 599 papers selected by a previous literature search. This group evaluated the results of this search in three work sessions, during which a level of evidence was assigned to each recommendation.

Analgesicos, antitermicos e antiinflamatorios nao hormonais: toxicidade - parte I / Analgesics, antipyretics and antiinflammatory drugs: toxicity - first part

Os medicamentos com acao analgesica, antitermica e antiinflamatoria(11) sao muito utilizados em adultos e criancas. Apesar de serem considerados medicamentos seguros, e de muitos analgesicos serem comercializados sem necessidade de prescricao medica, esses farmacos podem causar significantes eventos adversos, especialmente em criancas. Neste artigo, a autora apresenta uma revisao sobre a toxicidade desses medicamentos sobre diversos orgaos e enfatiza que muitos AA comercializados no Brasil ainda nao foram aprovados para uso infantil em outros paises, pois se desconhece a incidencia de seus efeitos adversos

Controle da dor do paciente com câncer / Pain control of the patients with cancer

Os autores enfatizam a importância do diagnóstico da causa da dor para aplicaçao da terapêutica adequada. Apresentam os medicamentos que podem ser utilizados, isoladamente ou em combinaçoes, evidenciando que o conhecimento das bases farmacológicas da terapêutica é necessário para a prescriçao correta dos analgésicos e medicamentos coadjuvantes.