Oral administration of eucalyptol reduces cell migration and pain-like behavior in zymosan-induced arthritis mice

Abstract Rheumatoid arthritis (RA) is an inflammatory disease that utilizes nonbiologic and biologic drugs for appropriate disease management. However, high cost, adverse effects, reduced effectiveness, and risk of infection have stimulated the search for safer and more efficacious therapeutic strategies. In the present study, we aimed to evaluate the anti-inflammatory and analgesic properties of eucalyptol in an experimental model of arthritis. Mice were administered zymosan or saline intra-articularly. One hour before the zymosan administration, the mice were treated with oral eucalyptol (200-400 mg/kg) and vehicle. Cell influx, neutrophils, lymphocytes, and monocytes were measured in joint exudates. Joint pain was assessed using paw-pressure tests. Orally administered eucalyptol (200 and 400 mg/kg) significantly reduced cell influx, as well as neutrophils, lymphocytes, and monocytes, when compared with the control. Eucalyptol at a dose of 400 mg/kg significantly reversed joint pain and demonstrated analgesic activity (60%); however, 200 mg/kg failed to alter joint pain. These results indicate that oral eucalyptol promotes anti-inflammatory and analgesic activity in mice subjected to zymosan-induced arthritis.

Efeitos de um minuto e dez minutos de deambulação em ratos com artrite induzida por adjuvante completo de Freund sobre os sintomas de dor e edema / Effects of one minute and ten minutes of walking activity in rats with arthritis induced by complete Freund's adjuvant on pain and edema symptoms

Este estudo avaliou o efeito de dois protocolos de exercício na nocicepção, edema e migração celular em ratos com artrite induzida por CFA. Ratos Wistar fêmeas (200 - 250 g, n = 50) foram induzidos à monoartrite por adjuvante completo de Freund (CFA, Mycobacterium butyricum; 0,5 mg/mL; 50 μL) na articulação do joelho direito (TF; n = 24) ou tornozelo direito (TT; n = 26). A incapacitação articular foi mensurada pelo tempo de elevação da pata (TEP; s) em 1 minuto de avaliação. O edema do joelho ou tornozelo foi avaliado pela medida do diâmetro articular (AD, cm) e pelo edema de pata (EP, mL), respectivamente. Ambos foram avaliados durante 10 dias consecutivos. Dois protocolos de exercício foram realizados: (a) exercício constante (TF, n = 6; TT, n = 6), realizando 1 minuto diário de exercício no cilindro (3 r.p.m.); (b) exercício variável (TF, n = 6; TT, n = 7), exercício com aumento de 1 minuto por dia, totalizando 10 minutos no último dia. Os grupos-controle (TF, n = 12; TT, n = 13) não realizaram exercício. Após 10 dias, os animais foram eutanasiados para contagem total (células/mm3) e diferencial (mononucleares e polimorfos nucleares; células/mm3) de leucócitos do tecido inflamado. O exercício variável inibiu a incapacitação e o edema em ambas as articulações. Entretanto, reduziu a migração total de leucócitos apenas na articulação TF. O exercício constante inibiu o edema nas duas articulações e reduziu a migração total de leucócitos da articulação TT. Porém, não reduziu a incapacitação. O exercício variável pareceu ser mais efetivo em reduzir os parâmetros inflamatórios em comparação com o exercício constante.

This study evaluated the effects of two protocols of exercise on nociception, edema and cell migration in rats with CFA-induced arthritis. Female Wistar rats (200 - 250 g, n = 50) was monoarthritis-induced by complete Freund's adjuvant (CFA; Mycobacterium butyricum, 0.5 mg/mL; 50 μL) into the right knee joint (TF; n = 24) or right ankle joint (TT; n = 26). Incapacitation was measured by the paw elevation time (TEP; s) in 1-min periods of observation. The edema of the knee or ankle joints was evaluated by the variation of the articular diameter (DA, cm) and by the paw volume variation (EP, mL), respectively. Both were measured during 10 consecutive days. Two protocols of exercise were performed: (a) in the constant exercise group (TF, n = 6; TT, n = 6) performing 1 minute of daily exercise on the cylinder; (b) variable exercise group (TF, n = 6; TT, n = 7), the exercise increased by 1 minute per day. The control groups (TF, n = 12; TT, n = 13) didn´t perform the exercise. After 10 days, the animals were euthanized for total (CT; cells/mm3) and differential leukocyte counts (mononuclear - MON, and polymorphonuclear - PMN, cells/mm3) of the articular inflammatory exudate. The variable exercise protocol inhibited incapacitation and edema for both joints. However, cell migration decreased only in the TF.The constant exercise reduced edema in both joints, and cell migration was decreased in the TT. However, the incapacitation was not reduced. Variable exercise seemed to be more effective in reducing the inflammatory parameters than constant exercise.

Analgesic Mechanism of Electroacupuncture in an Arthritic Pain Model of Rats: A Neurotransmitter Study

PURPOSE: We investigated what kinds of neurotransmitters are related with electroacupuncture (EA) analgesia in an arthritic pain model of rats. MATERIALS AND METHODS: One hundred rats were assigned to six groups: control, EA, opioid, adrenergic, serotonin and dopamine group. A standardized model of inflammatory arthritis was produced by injecting 2% carrageenan into the knee joint cavity. EA was applied to an acupoint for 30 min in all groups except fo the control group. In the opioid, adrenergic, serotonin and dopamine groups, each receptor antagonist was injected intraperitoneally to their respective group before initiating EA. RESULTS: In the opioid receptor antagonist group, adrenergic receptor antagonist group, serotonin receptor antagonist group, dopamine receptor antagonist group and the control group weight-bearing force decreased significantly from 30 min to 180 min after EA in comparison with the EA group. CONCLUSION: The analgesic effects of EA are related to opioid, adrenergic, serotonin and dopamine receptors in an arthritic pain model of rats.

Study of the inflammatory process induced by injection of carrageenan or formalin in the rat temporomandibular joint

O objetivo deste trabalho foi avaliar os efeitos da injecão de dois agentes flogísticos, ou seja, carragenina ou formalina, na ATM do rato, e a evolucão do quadro inflamatório provocado por essas substâncias. Foram utilizados 45 ratos, divididos em dois grupos experimentais e um grupo controle. Os animais foram sacrificados em lotes de três de cada grupo após três horas, 24 horas, três dias, sete dias e 15 dias da injecão. Histologicamente a reacão inflamatória em ambos os grupos experimentais iniciou-se com infiltrado inflamatório agudo, tornando-se misto e depois crônico. Sinais de hiperplasia da membrana sinovial foram observados aos três dias, intensos aos sete dias, estando presentes aos 15 dias somente no grupo da formalina. A injecão de solucão salina (grupo controle) não provocou reacão inflamatória. No presente trabalho foi concluído que uma injecão local única na região da ATM de carragenina ou de formalina foi suficiente para induzir reacão inflamatória na articulacão e nos tecidos moles periarticulares. As reacões inflamatórias resultantes da injecão desses agentes flogísticos foram semelhantes, mas o grupo da formalina mostrou infiltrado inflamatório mais persistente.

Reactions and their management.

The uneventful response to chemotherapy in leprosy is marked by clinically disturbing episodes encountered in 20-30% of patients and these phenomena are called "reactions". Generally they are classified as reversal reaction (type-1) and erythema nodosum leprosum (type-2). The cutaneous menifestations are: (1) Type-2 reactions in LL, BL types constituting erythema nodosum leprosum, erythema multiforme, erythema necroticans, subcutaneous nodules, lepromatous exacerbation. (2) Type-1 reactions in borderline and tuberculoid leprosy. The other manifestations include: Acute neuritis, lymphadenitis, arthritis, oedema of the hands and feet, ocular lesions, etc. Sequelae of reactions are: Paralytic deformities, non-paralytic deformities, extensive scarring and renal damage. A simple guideline to identify the risk-prone cases has been narrated. Prednisolone in standard dosage schedule as recommended by WHO is now being widely used in control programmes.

Efeito do veneno de abelha na artrite induzida por antígeno em coelhos / Effect of bee venom on antigen induced arthritis in rabbit

O efeito do veneno de abelha foi avaliado na artrite induzida por antígeno, em coelhos. O veneno de abelha foi ministrado 7 dias antes da indução da artrite, por via subcutânea, nas doses de 1,5; 3,0 e 6,0 mg/Kg/dia. O líquido sinovial foi coletado, para avaliação do número total e diferencial de células; permeabilidade vascular; determinação de prostaglandina E2 e metabólitos de óxido nítrico. A influência de glicocorticóides endógenos foi investigada com metopirona e RU 38 486, em animais que receberam veneno de abelha (1,5 mg/Kg/dia). O pré-tratamento com veneno de abelha (1,5 mg/Kg/dia) reduziu o influxo de leucócitos para a articulação inflamada, assim como os níveis de prostaglandina E2. Esse efeito não foi observado nos animais que receberam metopirona. O RU 38 486 não alterou a atividade antiinflamatória do veneno de abelha.The effect of bee venom was evaluated on antigen induced arthritis, in rabbits. Bee venom was administrated subcutaneously, 7 days before arthritis was induced, in different doses: 1,5; 3,0 and 6,0 g/Kg/day. Total and differential leucocyte migration, protein leakage, intraarticular concentration of prostaglandina E2 and nitric oxide metabolites were quantified in sinovial fluid. The influence of endogenous glucocorticoids was investigated with metyrapone and RU 38 486, in animals treated with bee venom (1,5g/Kg/day). Pre-treatment with bee venom (1,5g/Kg/day) were effective in reducing leucocyte afflux, compared with control animals. Prostaglandin E2 levels were also significantly reduced in this group. This effect was not observed in animals treated with metyrapone. The anti-inflammatory activity of bee venom was not affected by RU 38 486...

Ofloxacin induced arthropathy in patients with multi-drug resistance tuberculosis.

Some of the 4-fluroquinolones have been reported to induce arthropathy, but so far there are no case reports of arthropathy due to ofloxacin. Two cases of ofloxacin induced arthropathy in multi-drug resistance (MDR) tuberculosis are reported and possible drug interaction with other anti-tubercular drugs is discussed.

Ciprofloxacin in children: is arthropathy a limitation?

Two hundred and nineteen children treated with Ciprofloxacin were observed for drug related adverse reactions (ADR). ADR was observed in 35/219 (15.98%) children, arthropathy in 2/219 (0.9%) children only. All the ADR were reversible even on continuation of therapy except one child with arthropathy and no permanent sequele or death occurred as a drug related ADR.

Artrite induzida por antígeno em coelhos: padronizaçäo dos métodos de induçäo e avaliaçäo do processo inflamatório articular / Antigen-induced sothritis in ralbbit: standardization of the methods of induction and evaluation of the articular inflamatory process

Em 48 coelhos foi induzida artrite por injeçäo intra-articular de soro-albumina bovina, antígeno ao qual os animais haviam sido previamente imunizados de acordo com um protocolo bem definido: os animais foram sacrificados em grupos de três após períodos que variaram de uma hora a oito meses a contar da induçäo da artrite. O estudo do líquido e membranas sinoviais revelou inflamaçäo articular aguda nas primeiras 24 horas após a injeçäo intra-articular do antígeno: em 48 horas as características foram intermediárias entre um processo agudo e crônico, assumindo caráter crônico nos animais sacrificados a partir de entäo. Foram avaliados 11 parâmetros histopatológicos indicadores de sinovite: erosäo da camada de revestimento, proliferaçäo vascular, hemorragia, infiltrado inflamatório, nódulos linfóides, granulomas, dilataçäo e congestäo vascular, hiperplasia e hipertrofia da camada de revestimento, viscosidades, fibrose e vasculite; a presença de três ou mais desses parâmetros forneceu o melhor critério objetivo para o diagnóstico de sinovite. As alteraçöes histopatológicas encontradas foram semelhantes àquelas descritas em membrana sinovial de pacientes com doença reumatóide; a padronizaçäo deste modelo experimental propicia-nos meio de grande utilidade para o estudo dessa patologia humana