Individual variation is the key to the development of a vaccine against Staphylococcus aureus: a comparative study between mice lineages

Bacterial infections occur worldwide and are a major public health problem. Among pathogens, Staphylococcus aureus is the main causative agent of bacterial diseases in the world. This study aimed to evaluate which components of the immune system could act protectively against a S. aureus infection in intradermally immunized mice. C57BL/6 and A/j mice were immunized intradermally with S. aureus inactivated by heat and then challenged with viable strains in an air pouch model. At 6, 12, and 24 h after the challenge, euthanasia was performed, and the cellular profile of the inflammatory infiltrate, cytokines, and the bacterial load were evaluated in the air pouch lavages. Immunized mice demonstrated that the intradermal immunization with S. aureus promoted protection in C57BL/6 mice by reducing the bacterial, which was correlated with increased serum concentration of IgG antibodies (IgG1 and IgG2a) against S. aureus. The increase in IgG2a antibody levels was correlated with a decrease of bacterial load in intradermally immunized C57BL/6 mice, along with production of IL-17A at the inflammation site, as well as IgG1consumption. Similar results were not found in the A/j lineage. In conclusion, a vaccine against S. aureus should focus more on the individual characteristics of the host because it is a determinant factor for the success of the immunization.

Anti-inflammatory and membrane stabilizing properties of methyl jasmonate in rats / 中国天然药物

The present investigation was carried out to evaluate anti-inflammatory and membrane stabilizing properties of methyl jasmonate (MJ) in experimental rat models of acute and chronic inflammation. The effects of MJ on acute inflammation were assessed using carrageenan-induced rat's paw edema model. The granuloma air pouch model was employed to evaluate the effects of MJ on chronic inflammation produced by carrageenan in rats. The number of white blood cells (WBC) in pouch exudates was estimated using light microscopy. The levels of biomarkers of oxidative stress, such as malondialdehyde (MDA), glutathione (GSH) and activity of antioxidant enzymes in the exudates, were determined using spectrophotometry. The membrane stabilizing property of MJ was assessed based on inhibition of hemolysis of rat red blood cells (RBC) exposed to hypotonic medium. Our results indicated that MJ (25-100 mg·kg, i.p.) produced significant anti-inflammatory activity in carrageenan-induced paw edema in rats (P < 0.05). MJ reduced the volume of pouch exudates and the number of WBC in carrageenan-induced granulomatous inflammation. It also exhibited potent antioxidant and membrane stabilizing activities. In conclusion, these findings suggest the therapeutic potentials of methyl jasmonate in disease conditions associated with inflammation and its anti-inflammatory activity may be related to its antioxidant and membrane stabilizing activities.

Effect of Tanshinone on Inflammatory Response in Air-pouch Model Mice with Artificial Joint Aseptic Loosening / 中国药房

OBJECTIVE:To study the effect of tanshinone on inflammatory response in air-pouch model mice with artificial joint aseptic loosening. METHODS:Mice were randomly divided into blank control group(normal saline),titanium particle group (normal saline),tanshinone low-dose,medium-dose,high-dose groups(50,100,200 mg/kg),10 in each group. Air-pouch mod-els were induced. Except that mice were injected 0.5 mL normal saline into air-pouch in blank control group,other groups were in-jected 0.5 mL Titanium particle suspension(10 mg/mL)into air-pouch,continuously administrated medicines by 0.1 mL/10 g after 24 h,ig,for 14 d. After 24 h of last administration,the air-pouch was collected,air-pouch inflammation was observed by eyes and by microscopy after hematoxylin-eosin staining,and inflammatory cell density was calculated. Real-time quantitative poly-merase chain reaction method was conducted to detect the tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)mRNA expres-sion;enzyme-linked immunosorbent method was used to detect the TNF-α,IL-1β protein expression. RESULTS:Compared with blank control group,air-pouch swelling was obvious in titanium particle group,much exudation and neovascular were observed,in-flammatory response was severe,inflammatory cell density was increased significantly(P<0.05);TNF-α,IL-1β mRNA and pro-tein expression were obviously enhanced(P<0.05). Compared with titanium particle group,air-pouch swelling was relieved in tan-shinone doses groups,exudation and neovascular were decreased,inflammatory response was relieved,inflammatory cell density was decreased significantly(P<0.05);TNF-α,IL-1β mRNA and protein expression were obviously decreased(P<0.05),with a dose-dependent manner. CONCLUSIONS:Tanshinone can effectively inhibit the aseptic inflammatory response in air-pouch model mice with artificial joint aseptic loosening.

Anti-inflammatory, Antiarthritic and Antinociceptive Activities of 3,5-Disubstituted Thiazolidine Derivatives.

Aims: The aim of this study was to investigate the anti-inflammatory, antiarthritic and antinociceptive effects of two thiazolidinedione derivatives: 3-(2-bromo-benzyl)-5-(4- methylsufonyl-benzylidene)-thiazolidine-2,4-dione (LPSF/GQ-125) and 3-(2,6-difluorobenzyl)- 5-(4-methylsufonyl-benzylidene)-thiazolidine-2,4-dione (LPSF/GQ-192). Study Design: Study the effects of thiazolidinedione derivatives on the inflammatory process. Place and Duration of Study: Department of Antibiotics of the Federal University of Pernambuco, Brazil, between March 2010 and February 2012. Methodology: The carrageenan-induced air pouch in mice was performed and cytokine levels (TNF-α and IL-1β) were determined. Arthritis was induced in female wistar rats by complete Freund's adjuvant (CFA). To determine the antinociceptive activity, acetic acidinduced nociception and hot plate tests in mice were utilized. Results: Treatment with the compounds reduced leukocyte migration and the release of both TNF-α and IL-1β in the air pouch. Both LPSF/GQ-125 and LPSF/GQ-192 reduced the CFA-induced paw edema and the nociception induced by acetic acid; the hot plate test, however, showed no antinociceptive activity when compared to the control group. Conclusion: These results indicate that LPSF/GQ-125 and LPSF/GQ-192 exhibit promising anti-inflammatory, antinociceptive and antiarthritic activities related to their ability to inhibit TNF-α and IL-1β production as well as reduction of leukocyte migration.

Estudo comparativo da atividade antiinflamatória, ulcerogênica e citotóxica do S-ibuprofeno e ibuprofeno racêmico / Comparative study of anti-inflammatory, ulcerogenic and cytotoxic activities of racemate and S-ibuprofen

Ibuprofen is widely commercialized in racemic form. Although metabolic chiral inversion occurs through the conversion of R(-)-ibuprofen to S(+)-ibuprofen and the latter enantiomer is considered the active form, clinical trials involving the administration of a racemate to S-enantiomer dosage ratio of 1:0.5 have demonstrated that S(+)-ibuprofen is as efficacious as the racemic formulation. Moreover, the R(-)-enantiomer has been implicated in adverse gastrointestinal effects found with the racemic form, but the mechanisms involved in this process are not yet fully understood. The aim of the present study was to evaluate the anti-inflammatory activity of a racemate to S(+)-ibuprofen dosage ratio of 1:0.5 using the carrageenan air pouch model of inflammation and determine both ulcerogenic activity and the chiral conversion rate in rats. An in vitro study of the cytotoxicity of racemate and S(+)-ibuprofen in gastric cells was also performed. Although the plasma level of S(+)-ibuprofen was raised after racemate administration, no significant difference was found in anti-inflammatory activity, as assessed by exudate formation, PGE2 production and leukocyte migration to the air pouches. Fewer gastric lesions were found after S(+)-ibuprofen administration, despite the low gastric PGE2 content. In the in vitro study, the racemic compound proved more cytotoxic than S(+)-ibuprofen. The present findings suggest that the S-enantiomer of ibuprofen could be considered a therapeutic alternative to minimize gastrointestinal side effects, since the chiral inversion of R(-)-ibuprofen to S(+)-ibuprofen did not result in an improved anti-inflammatory response.

O Ibuprofeno é normalmente comercializado na forma racêmica. Embora ocorra inversão quiral convertendo a forma R(-)- em S(+)-ibuprofeno e, a última seja considerada a forma ativa, a administração da proporção 1:0,5 (racemato: S-enantiômero) demonstrou que o S(+)-ibuprofeno é mais eficaz que a formulação racêmica. Adicionalmente, o R(-)-enantiômero está envolvido nos efeitos adversos gastrintestinais descritos para a formulação racêmica, embora os mecanismos não sejam complemente compreendidos. O objetivo deste estudo foi avaliar a atividade antiinflamatória da proporção 1:0,5 (racemato:S-ibuprofeno) utilizando o modelo experimental de bolsa de ar, a atividade ulcerogênica e a taxa de conversão quiral em ratos. Também estudamos in vitro, a citotoxicidade provocada pelo racemato e S(+)-ibuprofeno em células gástricas. Embora os níveis plasmáticos de S(+)-ibuprofeno tenham aumentado após a administração do racemato, a atividade antiinflamatória avaliada pela formação de exsudato, produção de PGE2 e migração de leucócitos para a bolsa de ar não foram diferentes. As lesões gástricas foram reduzidas após a administração de S(+)-ibuprofeno, apesar da inibição de PGE2 gástrica. In vitro, o composto racêmico foi mais citotóxico que o S(+)-ibuprofeno. Nossos resultados sugerem que o S-enantiômero do ibuprofeno pode ser considerado uma alternativa terapêutica visando a redução dos efeitos colaterais gastrintestinais, visto que a inversão quiral do R(-)- para o S(+)-ibuprofeno não resultou em melhora do efeito antiinflamatório observado.

Atividade de tropaeolum majus l. sobre a mobilização e migração leucocitária em modelo de bolsão inflamatório / Activity of tropaeolum majus l. on the mobilization and leukocyte migration in an air pouch model

Tropaeolum majus L. (Tropaeolaceae) é uma importante planta medicinal conhecida popularmente no Brasil como chaguinha, capuchinha ou nastúrcio. Toda parte aérea da planta tem sido utilizada há séculos pela medicina popular. Suas folhas secas ou em infusão são usadas popularmente para o tratamento de várias doenças, incluindo processos inflamatórios. O objetivo do presente estudo foi avaliar o perfil da migração leucocitária em vigência de resposta inflamatória aguda, após um tratamento subcrônico com T. majus. Para isto, ratos Wistar machos foram tratados por cinco dias com três diferentes doses do extrato hidroetanólico (EHTM) obtido de T. majus (75, 150 e 300 mg/kg). Os animais controle receberam volume equivalente de solução salina (5,0 ml/kg) ou indometacina (5,0 mg/kg). Durante este período, os animais receberam 10 ml de ar estéril na cavidade subcutânea (air pouch) em três dias alternados. No quinto dia, uma hora após os tratamentos, a resposta inflamatória foi induzida com a administração de 1 ml de carragenina (solução 1%) na cavidade subcutânea, e 6 horas após, amostras de sangue e do exsudato foram coletadas para a determinação de leucócitos totais e para a realização da contagem diferencial. Os resultados demonstraram que a indometacina reduziu o número de leucócitos totais para o exsudato em aproximadamente 65%. O EHTM nas doses de 75 e 300 mg/kg também reduziram significativamente a migração destas células, com valores estimados em 23 e 40%, respectivamente. Estes resultados indicam uma possível atividade anti-inflamatória do T. majus neste modelo experimental, justificando, pelos menos em parte, o uso popular desta espécie.

Tropaeolum majus L. (Tropaeolaceae) is an important medicinal plant popularly known in Brazil as chaguinha, capuchinha or nasturtium. This species has been used for centuries in popular medicine. Dried leaves are popularly used in infusion for the treatment of various diseases, including inflammatory processes. The aim of this study was to assess the profile of leukocyte migration during an acute inflammatory response after a subchronic treatment with T. majus. For this purpose, male Wistar rats were treated for five days with three different doses of hydroalcoholic extract (HETM) obtained from T. majus (75, 150 and 300 mg/kg). Control animals received equivalent volume of saline solution (5.0 ml/kg) or indomethacin (5.0 mg/kg). During this period, the animals received 10 ml of sterile air in the subcutaneous cavity (air pouch) on three alternate days. On the fifth day, one hour after treatment, the inflammatory response was induced by administration of 1 ml carrageenan solution (1%) in the subcutaneous cavity, and 6 hours after, blood and exudate samples were collected for determination of total and differential leukocytes. The results showed that indomethacin reduced leukocyte migration in the exudates to about 65%. The HETM at doses of 75 and 300 mg/kg also significantly reduced the migration of these cells, with values ??of 23 and 40%, respectively. These results indicate a possible anti-inflammatory activity of T. majus in this experimental model, explaining, at least in part, the popular use of this species.

The effect of montelukast in a model of gouty arthritis induced by sodium monourate crystals / Efecto de montelukast en un modelo de artritis gotosa inducido por cristales de monourato de sodio

Non-steroidal anti-inflammatory drugs (NSAIDS) are the first line of therapy in acute gouty arthritis. NSAIDs inhibit the cyclooxygenase pathway, but not the lipooxygenase activity and can have many adverse effects and thus have a limited effect on the control of inflammation in this disease. In this work we studied the effect of montelukast on the cellular inflammatory infiltrate in a model of murine arthritis induced by sodium monourate crystals (SMU), using a subcutaneous air cavity (air pouch) in BALB/c mice. Seven groups of BALB/c mice (n = 4) were distributed into five experimental groups and two inflammatory control groups, a positive and a negative one. Previous to SMU exposure, the experimental groups received montelukast (1 and 0.01 mg/Kg/w) and/or indomethacine (2.5 mg/Kg/w), followed by administration of SMU in the air pouch. The total and differential counts of inflammatory cells were analyzed after 2, 6, 12 and 24 hours. Montelukast, significantly reduced the total number of cells (p<0.05), with a predominant impact on polymorphonuclear over mononuclear cells, especially after 12 hours of the medication. The montelukast/indometacine combination showed an additive effect. Our data show that montelukast has an anti-inflammatory effect in the model of gouty arthritis. Consequently, anti-leukotrienes could represent a new and effective therapy, either isolated or combined with conventional therapy of gouty arthritis.

En artritis gotosa aguda las drogas antiinflamatorias no esteroideas son la primera línea terapéutica. Este tratamiento no es satisfactorio porque inhibe la ciclooxigenasa sin modificar la actividad de la lipooxigenasa, y puede acompañarse de numerosos efectos adversos. Investigamos el efecto de montelukast sobre el infiltrado celular inflamatorio en un modelo de artritis múrida inducida por cristales de monourato de sodio (MUS) en el modelo experimental de la bolsa de aire (air pouch). Siete grupos de ratones BALB/c (n = 4) fueron distribuidos en cinco grupos experimentales y dos grupos controles inflamatorios: positivo y negativo. Los grupos experimentales recibieron, montelukast (1 y 0,01 mg/Kg/p) y/o indometacina (2,5 mg/Kg/p) por vía oral, previo a la administración de MUS en la bolsa del aire. El conteo absoluto y diferencial de las células inflamatorias fue analizado después de 2, 6, 12 y 24 horas de tratamiento. El tratamiento con montelukast redujo significativamente el número total de células presentes en el infiltrado inflamatorio (p < 0,05), con un efecto mayor sobre polimorfonucleares que sobre las células mononucleares, y con un máximo efecto a las 12 horas después de la administración del medicamento. La combinación montelukast/indometacina mostró un efecto aditivo. Los resultados demuestran que montelukast tiene un efecto antiinflamatorio en el modelo de la artritis gotosa. Por lo tanto, los anti-leucotrienos podrían representar una nueva y eficaz terapia, aislada o en combinación con la terapéutica convencional, para la artritis gotosa.

Erythromycin and alendronate inhibit aseptic loosening in murine osteolysis model / 中国矫形外科杂志

[Objective]To observe whether erythromycin and alendronate are effective in treating aseptic loosening in a murine osteolysis model. [Method]Air pouches were established in the back of BALB/c mice by injecting sterile air subcutaneously. After the air pouches were mature, grafts of calvaria from syngeneic mouse donors were implanted in the air pouches and polyethylene debris was injected into the air pouches. Mice were divided into 4 groups. In the first group, saline was injected into the air pouches.In the other three groups, polyethylene debris was used. Saline,erythromycin and alendronate were injected intraperitoneally separately.Pouch tissues were collected at 14 days after polyethylene debris administration for molecular and histologic analysis.[Result] Both erythromycin and alendronate inhibited osteoclastogenesis and bone resorption, but alendronate was not as effective as erythromycin in anti-inflammation.[Conclusion]Both erythromycin and alendronate can be promising drugs for the treatment of aseptic loosening.

A Clinical Comparison between Epidural Pressure Measurements and Intraventricular Pressure: Technical Note

OBJECTIVE: Measurement of intracranial pressure(ICP) is important in patients at risk of raised ICP. To evaluate the usefulness of measuring epidural pressure measurements for the estimation of intracranial pressure, we studied the relationship between epidural pressure and ventricular pressure. PATIENTS AND METHODS: From Nov. '97 to Jul. '98, 10 patients of extraventricular drainage(Group A) and 12 patients of decompressive craniectomy(Group B) are included in this study. Simultaneous recording of intracranial pressure (ICP) from an air-pouch epidural pressure monitoring system and a ventricular catheter was compared. RESULTS: The epidural pressure group(Group A) showed marked high epidural pressure(32.6+/-13.4mmHg) compared with those of intraventricular pressure, but in decompressive craniectomy group(Group B) shows nearly the same values(2.1+/-6.9mmHg). CONCLUSIONS: On the basis of the available comparison between these two methods of measuring intracranial pressure, in the light of the data we had established and the importance of ICP monitoring in neurosurgical critical care, intradural monitoring technique appears to be our measuring method of choice.