Evaluation of the relationship between blood cell markers and inflammation, disease activity, and general health status in ankylosing spondylitis

SUMMARY OBJECTIVE: The aim of this study was to assess the relation of systemic immune inflammation index, systemic inflammation response index, and systemic inflammation aggregate index with disease activity, functional status, and general health status in ankylosing spondylitis. METHODS: Patients with ankylosing spondylitis and healthy volunteers were included in this cross-sectional study. Demographic data; disease activity measurements such as the Bath Ankylosing Spondylitis Disease Activity Index, the Ankylosing Spondylitis Disease Activity Score with C-reactive protein, and the Ankylosing Spondylitis Disease Activity Score with erythrocyte sedimentation rate; functional status such as the Bath Ankylosing Spondylitis Functional Index; and general health status such as the Assessment of Spondyloarthritis International Society Health Index of the patients were recorded. C-reactive protein, erythrocyte sedimentation rate, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, systemic immune inflammation index, systemic inflammation response index, and systemic inflammation aggregate index values were recorded. Patients were grouped as active and remission according to the Bath Ankylosing Spondylitis Disease Activity Index score and as inactive-low and high-very high disease activity according to the Ankylosing Spondylitis Disease Activity Score. The correlation of laboratory parameters with disease-related parameters was tested. RESULTS: The indexes were significantly higher in patients compared to controls (p<0.001, for platelet to lymphocyte ratio p=0.03). No significant differences existed in any blood cell-derived indexes among patient groups categorized by disease activity (p<0.05 for all). Systemic immune inflammation index was weakly correlated with Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ρ=0.197 and p=0.049) and Ankylosing Spondylitis Disease Activity Score-erythrocyte sedimentation rate (ρ=0.201 and p=0.045). Systemic immune inflammation index was not correlated with Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and Assessment of Spondyloarthritis International Society Health Index. No correlation was found between other indexes and disease-related variables. Platelet to lymphocyte ratio, systemic immune inflammation index, systemic inflammation response index, and systemic inflammation aggregate index showed a weak positive correlation with C-reactive protein and erythrocyte sedimentation rate (ρ=0.200-0.381). CONCLUSION: Systemic immune inflammation index, systemic inflammation response index, and systemic inflammation aggregate index can be used to indicate systemic inflammatory burden in ankylosing spondylitis patients. However, these indexes are not effective in indicating patients' disease activity, general health status, and functional status.

Efectos biológicos protectores del ejercicio en modelos experimentales de tabaquismo: más allá de la cesación y la abstinencia / Protectives biological effects of exercise in animals models of tobacco smoking: beyond tobacco cessation and withdrawal

El tabaquismo es considerado una de las principales causas de morbilidad y mortalidad en la población general. En Chile la prevalencia de tabaquismo alcanza el 36,7% en hombres y 28,5% en mujeres. En este contexto, diversas estrategias farmacológicas y no farmacológicas han sido propuestas para promover la cesación de su consumo, así como para contrarrestar las comorbilidades asociadas al tabaquismo prolongado. Entre ellas, el ejercicio físico ha sido tradicionalmente considerado, por su impacto en la promoción de la cesación del hábito tabáquico, así como también por sus efectos en la reducción de las manifestaciones clínicas del síndrome de abstinencia post cesación. No obstante, estudios realizados en modelos animales durante los últimos 10 años han proporcionado datos contundentes para sustentar la hipótesis de que la práctica regular de ejercicio físico sería también efectiva para prevenir o modular el estrés oxidativo y la respuesta inflamatoria inducida por el tabaco, previniendo el deterioro orgánico de los sistemas fisiológicos expuestos. Esta revisión tiene por objetivo discutir la evidencia publicada respecto a los efectos biológicos inducidos por ejercicio físico y su impacto en la reversión de los mecanismos fisiopatológicos que subyacen a las comorbilidades asociadas al hábito tabáquico, focalizando el análisis en los mecanismos de estrés oxidativo y respuesta inflamatoria del sistema respiratorio y cardiovascular.

Smoking is considered one of the main causes of morbidity and mortality in the general population. In Chile, the prevalence of smoking reaches 36.7% in men and 28.5% in women. In this context, several pharmacological and non-pharmacological strategies have been proposed to promote the cessation of their use, as well as to counteract the comorbidities associated with prolonged smoking. Among them, physical exercise has been traditionally considered, due to its impact on the promotion of cessation of smoking, as well as its effects in reducing the clinical manifestations of withdrawal syndrome. However, studies conducted in animal models during the last 10 years have provided strong data to support the hypothesis that regular practice of physical exercise would also be effective in preventing or modulating oxidative stress and the inflammatory response induced by tobacco, preventing the organic deterioration of exposed physiological systems. The objective of this review is to discuss the published evidence regarding the biological effects induced by physical exercise and its impact on the reversion of the pathophysiological mechanisms underlying the comorbidities associated with smoking, focusing the analysis on the mechanisms of oxidative stress and inflammatory response of the respiratory and cardiovascular system.

Efeito do extrato insaponificável de abacate e soja na doença periodontal induzida, na osseointegração de implantes e no reparo de defeitos críticos de calvaria de ratos / Effect of the avocado/soybean unsaponifiables on the induced periodontitis, on the osseointegration, and on the critical sized calvaria bone defect repair in rats

Esse estudo teve como objetivo avaliar, em ratos, a influência da utilização do extrato de óleo insaponificável de abacate e soja (ASU) no reparo da periodontite induzida por ligaduras, na osseointegração de implantes e na integração de biomateriais osteocondutores. Para isso foram avaliadas as hipóteses de que o ASU poderia: 1)Aumentar o reparo da periodontite induzida; 2)Favorecer o reparo associado ao tratamento da periodontite induzida; 3)Acelerar a osseointegração; 4)Influenciar na integração de enxertos osteocondutores. Para a avaliação da primeira hipótese foram utilizados 84 ratos que foram submetidos a indução da periodontite por meio de ligaduras e que foram randomicamente divididos em 4 grupos: CTR: Administração do soro fisiológico(SS) no mesmo dia da indução da periodontite; ASU/-7: Administração de ASU iniciada 7 dias antes da indução de periodontite(0.6 mg/kg); ASU/0: Administração de ASU iniciada no dia da indução da periodontite; ASU/+7: Administração do ASU iniciada no dia da remoção da ligadura. As ligaduras, que foram inseridas bilateralmente nos segundos molares superiores, foram removidas após 7 dias e os medicamentos foram administrados diariamente por gavagem até o sacrifício dos animais (7, 15 e 30 dias). Foram realizadas análise microtomográfica (%volume ósseo), histomorfométricas (% osso na região da furca, distancias da junção cemento-esmalte(JCE) ao topo da crista óssea(CO) e a porção apical do epitélio juncional (aJE), imunohistoquímica (TRAP, RANKL e Fosfatase Alcalina) e de qPCR (IL1ß, IL6,TNFα, RANKL e Fosfatase Alcalina). Para avaliação da segunda hipótese foram utilizados 84 ratos que foram submetidos a indução da periodontite por meio de ligaduras e que foram randomicamente divididos em 4 grupos: SRP-Administração de SS no dia do tratamento; SRP/ASU-7: Administração do ASU iniciada 7 dias antes da indução da periodontite(0.6 mg/kg); SRP/ASU00: Administração do ASU iniciada no dia da indução da periodontite; SRP/ASU+7: Administração do ASU iniciada no dia do tratamento da periodontite. A remoção da ligadura e a raspagem foram executados 7 dias após a indução da periodontite e os medicamentos foram administrados diariamente por gavagem até o sacrifício dos animais (7,15 e 30 dias). Foram executadas as mesmas análises utilizadas para o estudo da primeira hipótese. Para a avaliação da terceira hipótese, foram instalados 1 implante por tíbia em 30 ratos que foram randomicamente divididos em 3 grupos: ASU1: Administração de ASU iniciada 7 dias antes de instalação dos implantes(0.6 mg/kg); ASU2: Administração de ASU iniciada no dia da instalação dos implantes; CTL: Administração de SS iniciada no dia da instalação do implantes. Os medicamentos foram administrados diariamente por gavagem até o sacrifício dos animais (60 dias). Foram executadas análises radiográficas, biomecânicas, histomorfométrica (Contato osso-implante(%BIC) e área de osso entre as roscas(%BBT), histológica descritiva e imunohistoquímica (BMP2, TGFß1 e Osteocalcina). Para avaliação da quarta hipótese foram executados defeitos críticos em calotas (DCC-5mm) de 84 ratos que foram randomicamente divididos em 2 grupos: CTR-Administração de SS e ASU: Administração de ASU(0.6 mg/kg). Adicionalmente os animais foram divididos em 3 subgrupos de acordo com o biomaterial utilizado para preencher o defeito: COA-Defeito preenchido com coágulo; OBD-Defeito preenchido com osso bovino desproteinizado; TCP/HA- Defeito preenchido com ß-fosfato tricálcio/Hidroxiapatita. A administração dos medicamentos foi iniciada 15 dias antes da confecção dos DCC e foram aplicados diariamente por gavagem até o sacrifício dos animais (15 e 60 dias). Foram executados análise microtomográfica (%osso e biomaterial), histologia descritiva e histomorfométrica (%osso, biomaterial e tecido conjuntivo). No estudo I foi verificado que os grupos ASU0 e ASU+7 apresentaram maiores porcentagens de tecido ósseo na região da furca e menores distâncias JCE-CO que o grupo CTR nos períodos de 7 e 15 dias. Adicionalmente foi verificada uma maior expressão de IL-1ß, RANKL e TRAP e menor expressão de fosfatase alcalina no grupo CTR em relação ao grupo ASU+7. No estudo II foi verificado que não houve diferenças entre os grupos com relação as análises histométrica e microtomográfica. Foi verificado uma maior expressão do RNAm de fosfatase alcalina no grupo SRP/ASU+7 em relação aos outros grupos aos 30 dias, e menor expressão do RNAm de RANKL nos grupos SRP/ASU0 e SRP/ASU+7 em relação aos grupos SRP e SRP/ASU-7 aos 15 dias. No estudo III os grupos de animais dos grupos ASU1 e ASU2 apresentaram maiores valores de %BIC na região cortical e maior expressão de BMP2 e TGFß1 em relação ao grupo CTL. No estudo IV ocorreu uma maior formação óssea no grupo ASU em relação ao grupo CTR no subgrupo COA, porém não houve diferenças entre os grupos subgrupos OBD e a TCP-HA. Dessa forma pode-se concluir que o extrato de ósseo insaponificável de abacate e soja promoveu maior reparo na periodontite induzida em ratos, porém esses resultados não foram consistentes pois esse efeito não foi confirmado no modelo de tratamento da periodontite induzida. Esse medicamento induziu, de forma sutil uma aceleração da osseointegração de implantes e uma maior formação óssea associada a DCC que não foram preenchidos com biomateriais

The aim of this study was to evaluate in rats the effect of the avocado soybean unsaponifiables (ASU) on the bone repair in induced periodontitis, on the osseointegration of dental implants, and on the repair of the critical sized calvaria defects filled or no with biomaterials. For this purpose, the following hypothesis regarding the use of ASU were tested: 1)Improve the periodontal repair in induced periodontitis; 2)Improve the periodontal repair after the treatment of the induced periodontitis; 3) Accelerate osseointegration; 4) Improve the integration of osteoconductors bone grafts in the critical size calvaria defects. For the evaluation of the first hypothesis, eighty-four animals were randomly assigned into four equally-sized groups, receiving daily by gavage either sterile saline (CTR) or ASU (0.6 mg/kg), starting either 7 days prior to- (ASU/-7), or on the day- (ASU/0), or 7 days after (ASU/+7) periodontitis induction. Periodontitis was induced by placing silk ligatures into the gingival sulcus of the second maxillary molars for 7 days; thereafter the ligatures were removed. Seven animals from each group were euthanized at 7, 15 or 30 days after ligature removal. Bone resorption was evaluated by histomorphometry and micro CT. Immunohistochemistry was used to evaluate TRAP, RANKL, Alkaline phosphatase and qPCR to evaluate IL-1ß, TNF-α, IL-6, RANKL, Alkaline phosphatase (AP). For the evaluation of the second hypothesis, periodontitis was induced in 84 rats via ligature placement around the second upper molar, which was removed after 7 days, and scaling was performed at this time. Subsequently, the rats were randomly allocated to four groups with 21 animals each: One in which saline solution (SS) was administered (SRP) and three in which ASU was administered (0.6 g/kg/day), beginning either 7 days before the induction of periodontitis (SRP/ASU-7), on the day of periodontitis induction (SRP/ASU0), or on the day of treatment (SRP/ASU+7). The ASU and SS were administered daily by gavage until the sacrifice of the animals (7, 15, and 30 days). The analysis performed was the same of the evaluation of the first hypothesis. For the evaluation of the third hypothesis, thirty rats were randomly assigned into one of three equal-sized groups: 1) ASU1; administration of ASU, starting 7 days prior to implant installation, 2) ASU2; administration of ASU, starting on the day of implant installation, and 3) CTL; administration of saline solution. In all animals, one titanium implant was placed in each tibia. All animals received ASU or saline solution by gavage daily until sacrifice 60 days post-operatively. Implant osseointegration and bone maturation were assessed by biomechanical analysis, radiographic bone density, descriptive histology, immunohistochemical analysis for bone morphogenetic protein 2 (BMP2), transforming growth factor beta 1 (TGFß1), and osteocalcin (OCN), histomorphometric evaluation of bone-to-implant contact (BIC) and mineralized bone area fraction within the threads of the implant (BA). For the evaluation of the forthy hyphotesis, one critical sized calvaria defect (CCD-0.5 mm) was made in each of 84 rats. These defects were filled with coagulum (COA), deproteinized bovine bone (DBB), and ß-tricalcium phosphate/hydroxyapatite (TCP/HA). ASU (0.6 g/kg) or saline solution (CTR) was administered daily by gavage from 15 days before surgery until the animals were euthanized 15 or 60 days after surgery (7 animals per period/group). The description and composition of the tissues that filled the CCDs were analyzed by micro CT and histomorphometry. It was showed in the study I that the histomorphometry and micro CT showed larger bone resorption in the CTR than in the ASU/0 (15 days), and ASU/+7 (7 and 15 days). CTR presented also with a higher expression of TRAP (15 and 30 days) and RANKL (7 and 15 days) comparing to ASU/0 and ASU/+7. Similarly, qPCR showed higher levels of RANKL and IL1ß and lower levels of AP in CTR comparing with all other groups (All periods). In the study II, the SRP/ASU+7 presented higher expression of the alkaline phosphatase than all the other groups at 30 days. The SRP/ASU0 and SRP/ASU+7 groups presented lower expression of RANKL mRNA than the groups SRP e SRP/ASU-7 at 15 days. However, there were no differences between the groups regarding the percentage of bone fill and in the expression of the proteins. In the study III, ASU1 and ASU2 showed a 3- and 9- times higher expression of BMP2 and TGFß1, respectively, compared to CTL (p<0.05). Histomorphometric analysis, however, showed that both ASU1 and ASU2 groups presented significantly higher BIC values only in the cortical bone compartment when compared to CTL (p<0.05). In the study IV, the percentage of bone fill in the CCD of the COA-ASU group was significantly higher than that in the COA-CTR group at both evaluated time points (p<0.05). There were no differences regarding the percentage of bone between the DBB-ASU and DBB-CTR groups and the TCP/HA-ASU and TCP/HA-CTR groups at either time point (p<0.05). It can be concluded that the ASU can improve the repair of the induced periodontitis, but this effect was inconsistent since the ASU effects were not confirmed in the treatment of the induced periodontitis. ASU consumption has only a subtle effect on implant osseointegration and induced an enhancement in bone formation in the CCDs filled with coagulum

Early treatment with high-volume hemofiltration combined with rhubarb for patients with severe acute pancreatitis / 第二军医大学学报

Objective: To investigate the effect of early treatment with a combination of rhubarb and high volume hemofiltration for patients with severe acute pancreatitis(SAP). Methods: We retrospectively analyzed the 31 SAP patients, who were treated in our department between June 2005 and December 2007. Twelve patients (control group) received high-volume hemofiltration only and the other 19 patients(treatment group)received both hemofiltration and rhubarb-enchyma infused via a gastric tube for three days. The vital signs and recovery of gastrointestinal functions were observed in the two groups. The serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and plasma endotoxin were measured in the two groups. Results: The vital signs of all the patients were stable during the treatment. The APACHE II score and serum cytokine concentrations were significantly decreased in the two groups after treatment(P0.05). Gastrointestinal function of the treatment group recovered earlier, with an effective rate significantly higher than that of the control group(P<0.05). The plasma endotoxin of the control group were gradually elevated during the treatment; that of the treatment group increased first and then gradually decreased; and there was significant difference between the two groups (P<0.05). Conclusion: High-volume hemofiltration can clear the plasma inflammatory mediators and cytokines. Rhubarb can improve the gastrointestinal function and decrease the plasma endotoxin level of SAP patients; early treatment with a combination of both can improve the clinical outcomes of patients.

Regulatory Effect of Qing Yi Tang on Inflammatory Response in Rats with Acute Pancreatitis and Endotoxemia / 中华医院感染学杂志

OBJECTIVE To study the effect of Qing Yi Tang on acute pancreatitis(AP),especially AP complicated with endotoxemia and its possible mechanism.METHODS Fourty Wistar rats were divided into 5 groups including group A(the control group),group B(the AP group),group C(the AP group treated with Qing Yi Tang),group D(the AP group treated with LPS) and group E(the AP group treated with LPS + Qing Yi Tang).Pathological damage of pancreatic tissue was scored with HE staining.The mRNA expression of TNF-? was measured with semi-quantitative RT-PCR,and activation of NF-?B was detected with flow cytometry(FCM) assay.RESULTS It was shown in results that the expression of TNF-? mRNA,activation of NF-?B and pathological damage of the group B were all obviously higher than those of the group A.After treated with LPS which might promote the activation of NF-?B,there was seen the further rise of the activation of NF-?B,expression of TNF-? mRNA and pathological damage.When Qing Yi Tang intervention was applied,the activation of NF-?B and the expression of TNF-? mRNA could be remarkably relieved,so did the pathological damage of pancreas.CONCLUSIONS Qing Yi Tang may be applied to decrease activation of NF-?B and the expression of TNF-? so as to treat AP or AP with endotoxemia.