Interleukin-17 plays a role in dental pulp inflammation mediated by zoledronic acid: a mechanism unrelated to the Th17 immune response?

Abstract Objective To evaluate the influence of RORγT inhibition by digoxin on inflammatory changes related to interleukin-17 (IL-17) in the pulp of rats treated with zoledronate (ZOL). Methodology Forty male Wistar rats were divided into a negative control group (NCG) treated with saline solution, a positive control group (PCG) treated with ZOL (0.20 mg/kg), and three groups treated with ZOL and co-treated with digoxin 1, 2, or 4 mg/kg (DG1, 2, and 4). After four intravenous administrations of ZOL or saline solution in a 70-day protocol, the right molars were evaluated by histomorphometry (number of blood vessels, blood vessels/µm2, cells/µm2, total blood vessel area, and average blood vessel area) and immunohistochemistry (IL-17, TNF-α, IL-6, and TGF-β). The Kruskal-Wallis/Dunn test was used for statistical analysis. Results PCG showed an increase in total blood vessel area (p=0.008) and average blood vessel area (p=0.014), and digoxin treatment reversed these changes. DG4 showed a reduction in blood vessels/µm2 (p<0.001). In PCG odontoblasts, there was an increase in IL-17 (p=0.002) and TNF-α (p=0.002) immunostaining, and in DG4, these changes were reversed. Odontoblasts in the digoxin-treated groups also showed an increase in IL-6 immunostaining (p<0.001) and a reduction in TGF-β immunostaining (p=0.002), and all ZOL-treated groups showed an increase in IL-17 (p=0.011) and TNF-α (p=0.017) in non-odontoblasts cells. Conclusion ZOL induces TNF-α- and IL-17-dependent vasodilation and ectasia, and the classical Th17 response activation pathway does not seem to participate in this process.

Effects of femtosecond laser assistcataract extraction on the levels of inflammatory factors in aqueous humor, corneal perception and high order aberration / 中国医师进修杂志

Objective:To investigate the effects of femtosecond laser assistcataract extraction on the levels of inflammatory factors in aqueous humor, corneal perception and high order aberration.Methods:Forty-eight patients (56 eyes) undergoing cataract surgery in the Shouguang People′s Hospital from June 2018 to February 2020 were enrolled in this study, and they were divided into observation group (24 patients and 27 eyes, femtosecond laser cataract phacoemulsification) and control group (24 patients and 29 eyes, coaxial microincision phacoemulsification) by random number table method. The levels of prostglndin E2 (PGE2), interleukin (IL)-6 and IL-1β in aqueous humor were detected before and after operation. Upper corneal and central corneal perception thresholds were recorded before surgery, 7 d after surgery, 1 month after surgery and 3 months after surgery. High order aberrations of the whole eye and cornea at 4mm pupil diameter before and after operation were recorded.Results:After operation, the levels of PGE2, IL-6 and IL-1β in aqueous humor in the observation group were lower than those in the control group: (45.62 ± 5.71) ng/L vs. (63.65 ± 5.62) ng/L, (15.25 ± 3.21) ng/L vs. (24.59 ± 6.13) ng/L, (17.16 ± 1.28) ng/L vs. (25.74 ± 4.62) ng/L, the differences were statistically significant ( P<0.05). The upper and central corneal perception threshold of observation group after operation for 7 d were higher than those in the control group: 4.55 ± 0.50 vs. 4.20 ± 0.33, 5.68 ± 0.49 vs. 5.52 ± 0.45, the differences were statistically significant ( P<0.05). The indexes of high order aberration of the whole eye decreased in the two groups ( P<0.05), while the indexes of cornea did not change significantly. The indexes of high order aberration of the whole eye and cornea between before and after surgery between the two groups had no significant differences ( P>0.05). Conclusions:Femtosecond laser assist cataractextraction can relieve inflammation, reduce the whole eye high order aberration, but not affect the cornea, and can improve corneal perception.

A Case of Acute-phase Reaction of Denosumab which was Difficult to Exclude Aggravation of Original Cancer Pain

Introduction: We report a case of acute-phase reaction of denosumab which was difficult to exclude aggravation of original cancer pain. Case: A 65 year-old man with severe pain from right back to upper abdomen due to mid thoracic vertebral metastases of small cell lung cancer was consulted to palliative care team. Denosumab 120 mg was administered subcutaneously three times every four weeks. On the next day of first administration, pyrexia occurred. At all three administrations, pain worsened for four days after the next day of administration. The pain was worsened from numerical rating scale 2 to 6. Same phenomenon was observed each time denosumab was administered for three consecutive times. Although the area of pain overlapped with that of original vertebral metastases, the repetition of the pain exacerbation soon after the denosumab administration suggested acute-phase reaction. Conclusion: Pain aggravation caused by acute phase reaction of denosumab might be overlooked in patients with cancer pain. More investigation is needed for details of acute-phase reaction caused by denosumab.

Effect of elastic-band exercise on muscle damage and inflammatory responses in Taekwondo athletes / Efeito do exercício com banda elástica sobre a lesão muscular e as respostas inflamatórias em atletas de Taekwondo / Efectos de los ejercicios con banda elástica sobre la lesión muscular y las respuestas inflamatorias en atletas de Taekwondo

INTRODUCTION: Elastic bands offer variable elastic resistance (ER) throughout a range of motion and their incorporation with exercise movements has been used for variable strength training and rehabilitation purposes. Objective: Investigate the effect of acute bout of progressive elastic-band exercise on muscle damage and inflammatory response in Taekwondo athletes (TKD) compared with untrained ones.METHODS: Fourteen (TKD, n = 7 and untrained, n = 7) men performed 3 sets of progressive resistance elastic exercise. Blood samples were taken pre-exercise and also immediately and 24h post exercise. Delayed onset muscle soreness (DOMS), creatine kinase (CK) and lactate dehydrogenase (LDH) activity, total leukocyte counts, interleukin-6 and C-reactive protein (CRP) were analyzed.RESULTS: Only DOMS increased in untrained group, but elevation of DOMS was observed in both groups (TKD and untrained) at 24h after exercise (p<0.05). CK and LDH activity increased in both groups significantly. Also TKD group only showed CK increasing 24h post exercise (p<0.05). Total circulating leukocyte counts increased immediately in post exercise experiments and decreased in 24h ones in both groups (p<0.05). Serum IL-6 immediately increased in both groups and 24h post exercises but there was no significant difference between immediate and 24h post exercise experiments in TKD group. Furthermore, CRP just increased 24h after exercise in both groups (p<0.05).CONCLUSION: Progressive resistance elastic exercise induced muscle damage and inflammation in TKD athletes, but also had smaller changes in comparison with untrained group and other forms of exercise.

INTRODUÇÃO: As bandas elásticas oferecem resistência elástica (RE) variável em toda a amplitude de movimento, e sua incorporação aos movimentos de exercício tem sido utilizada para fins variáveis de treinamento de força e de reabilitação. Objetivo: Investigar o efeito de ciclos agudos de exercício progressivo com banda elástica sobre os danos e respostas inflamatórias dos músculos em atletas de Taekwondo (TKD), em comparação com os indivíduos não treinados.MÉTODOS: Catorze (TKD, n=7 e não treinados, n=7) homens realizaram três conjuntos de exercício elástico com resistência progressiva. Foram coletadas amostras de sangue antes, imediatamente após e 24 horas depois do exercício. Procederam-se às seguintes análises: dor muscular de início tardio (DMIT), atividade da creatina quinase (CK) e da lactato desidrogenase (LDH), contagem total de leucócitos, interleucina-6 e proteína C reativa (CRP).RESULTADOS: Só a DMIT aumentou no grupo não treinado, mas a elevação desse parâmetro foi constatada em ambos os grupos (TKD e não treinados) 24 horas depois do exercício (p < 0,05). A atividade da CK e da LDH aumentou significantemente nos dois grupos. Além disso, o grupo TKD só apresentou elevação da CK 24 horas depois do exercício (p < 0,05). As contagens totais de leucócitos circulantes aumentaram imediatamente nas experiências pós-exercício e caíram nas experiências às 24 horas em ambos os grupos (p < 0,05). A IL-6 sérica aumentou de imediato nos dois grupos e 24 horas depois dos exercícios, mas não se constatou diferença significante entre as experiências imediatas e depois de 24 horas no grupo TKD. Além disso, a CRP aumentou apenas 24 horas após o exercício nos dois grupos (p < 0.05).CONCLUSÃO: O exercício progressivo com banda elástica induziu danos musculares e inflamação nos atletas de TKD, tendo porém, alterações menores em comparação com o grupo não treinado e com outras formas de exercício.

INTRODUCCIÓN: Las bandas elásticas ofrecen resistencia elástica (RE) variable en toda la amplitud de movimiento, y su incorporación a los movimientos de ejercicios ha sido utilizada para fines variables de entrenamiento de fuerza y de rehabilitación. Objetivo: La finalidad del presente estudio fue investigar el efecto de ciclos agudos de ejercicios progresivos con banda elástica sobre los daños y respuestas inflamatorias de los músculos en atletas de Taekwondo (TKD), en comparación con los individuos no entrenados.MÉTODOS: Catorce (TKD, n=7 y no entrenados, n=7) hombres realizaron tres conjuntos de ejercicios elásticos con resistencia progresiva. Fueron colectadas muestras de sangre antes, inmediatamente después y 24 horas después de los ejercicios. Se procedió a realizar los siguientes análisis: dolor muscular de inicio tardío (DMIT), actividad de creatincinasa (CK) y de lactato deshidrogenasa (LDH), conteo total de leucocitos, interleucina-6 y proteína C reactiva (CRP).RESULTADOS: Sólo la DMIT aumentó en el grupo no entrenado, pero la elevación de ese parámetro fue constatada en ambos grupos (TKD y no entrenados) 24 horas después de los ejercicios (p < 0,05). La actividad de la CK y de la LDH aumentó significantemente en los dos grupos. Además, el grupo TKD sólo presentó elevación de la CK 24 horas después de los ejercicios (p < 0,05). Los conteos totales de leucocitos circulantes aumentaron inmediatamente en los experimentos post-ejercicio y cayeron en los experimentos a las 24 horas en ambos grupos (p < 0,05). La IL-6 sérica aumentó de inmediato en los dos grupos y 24 horas después de los ejercicios, pero no se constató diferencia significativa entre los experimentos inmediatos y después de 24 horas en el grupo TKD. Además de eso, la CRP aumentó solamente 24 horas después de los ejercicios en los dos grupos (p < 0.05).CONCLUSIÓN: Los ejercicios progresivos con banda elástica indujeron daños musculares e inflamación en los atletas de TKD habiendo, no obstante, alteraciones menores en comparación con el grupo no entrenado y con otras formas de ejercicio.

Reação de fase aguda e sua relação com o desempenho de cavalos em competição de longa distância / Acute phase reaction and its relationship with performance horses competing long distance

O exercício físico é um dos estímulos fisiológicos mais estressantes que um animal pode sofrer e, dependendo de sua intensidade, sugere-se que possa gerar uma reação mediada por proteínas de fase aguda (PFA). O objetivo deste estudo foi caracterizar a reação de fase aguda e sua relação com o desempenho de cavalos submetidos a uma competição de longa distância. O experimento foi desenvolvido durante a Marcha de Resistência anual promovida pela Associação Brasileira de Criadores de Cavalos Crioulos (ABCCC), composta por um percurso de 750km percorrido durante 15 dias. Foram avaliados 23 equinos, os quais foram divididos em dois grupos, sendo o grupo 1 composto pelos 10 primeiros colocados na competição e o grupo 2 formado pelos 13 animais que concluíram a competição em colocações inferiores ou foram desclassificados antes de terminar a prova. Efetuaram-se coletas sanguíneas em repouso (dia 0) e no último dia de competição, e foi realizado o teste de eletroforese em gel de poliacrilamida contendo dodecil sulfato de sódio (SDS-PAGE) para identificar as proteínas (albumina, haptoglobina, ceruloplasmina, transferrina, imunoglobulina G, imunoglobulina A, glicoproteína ácida e proteína de peso molecular de 23kDa). Os resultados demonstraram que o exercício físico imposto influenciou de forma significativa (P<0,0001) as concentrações séricas de haptoglobina, ceruloplasmina, imunoglobulina A, glicoproteína ácida e proteína de peso molecular de 23kDa. Quando comparados os resultados dos grupos estudados, observou-se que a concentração de haptoglobina após a competição foi superior no grupo de animais com baixo desempenho (grupo 2). Conclui-se que a competição de longa duração é capaz de gerar reação de fase aguda e que o monitoramento da concentração de haptoglobina pode ser um sinalizador de processo inflamatório e baixo desempenho.(AU)

Exercise is one of the most stressful physiologic stimuli that an animal might suffer, depending on its intensity it may generate a reaction mediated by acute phase proteins (APP). The aim of this study was to characterize the acute phase reaction and its relation to performance horses subjected to long distance competition. The experiment was conducted during the annual March of Resistance promoted by the Brazilian Association of Crioulo Horse Breeders (ABCCC), composed of a 750km route traveled during 15 days. 23 horses which were divided in two groups, one group composed by the 10 best placed horses and the second group consisting of 13 animals that have completed the competition in other positions or were disqualified before concluding the race were evaluated. All horses at the beginning of the competition (day 0) and on the last day of competition were subjected to collection of blood and SDS-polyacrylamide gel (SDS-PAGE) electrophoresis was used to measure APPs concentrations (albumin, ceruloplasmin, transferrin, haptoglobin, acid glycoprotein, immunoglobulin G, immunoglobulin A and a protein with molecular weight of 23 kDa). By the evaluation of the results, it was observed that exercise had a highly significant influence (P<0.0001) in the serum concentrations of the ceruloplasmin, haptoglobin, acid glycoprotein, immunoglobulin A and protein with molecular weight of 23kDa. When comparing the results of the study groups it was observed that the concentration of haptoglobin after the competition was higher in the group of animals with low performance (group 2). We conclude that the long term competition is able to generate acute phase reaction and monitoring the concentration of haptoglobin may be an indicator of inflammation and low performance.(AU)

Comparison of short-term outcomes and acute inflammatory response between laparoscopy-assisted and totally laparoscopic distal gastrectomy for early gastric cancer

PURPOSE: Laparoscopic gastrectomy is widely used to treat early gastric cancer. The advantages of totally laparoscopic distal gastrectomy (TLDG) are unproven, and some concerns remain regarding the early surgical outcomes due to its technical difficulty. We compared the early surgical outcomes and acute inflammatory response between patients undergoing TLDG and laparoscopy-assisted distal gastrectomy (LADG) for treatment of early gastric cancer. METHODS: We performed a retrospective study on 212 consecutive patients who underwent laparoscopic distal gastrectomy for gastric cancer between January 2008 and June 2014. A total of 179 LADG cases and 33 TLDG cases were included. After age, sex, body mass index, and American Society of Anesthesiologists physical status score were matched using propensity score matching (PSM), we compared the short-term surgical outcomes between the LADG and TLDG groups. RESULTS: The TLDG group had a shorter hospital stay (9.5 days vs. 11.0 days, P = 0.046) and less blood loss (116.6 mL vs. 141.5 mL, P = 0.031) than those in the LADG group. There were no differences in the preoperative WBC count and CRP level and the other clinical data between the two groups after PSM. Postoperative WBC count, serum CRP level, and decrease rate of WBC count in the TLDG group were significantly lower than those in the LADG group. CONCLUSION: The short-term outcomes of TLDG revealed better than that of LADG in this study. Therefore, TLDG is one of the safe and feasible procedure for the treatment of early gastric cancer.

Systemic lupus erythematosus activity and beta two microglobulin levels / Atividade do lúpus eritematoso sistêmico e níveis de beta dois microglobulina

CONTEXT AND OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease with a cyclical clinical course. Evaluation of the clinical activity of this disease is important for choosing the correct treatment. The objective of this study was to analyze the value of beta-2 microglobulin (β2M) serum levels in determining SLE clinical activity. DESIGN AND SETTING: Cross-sectional analytical study conducted at the rheumatology outpatient clinic of a private university hospital. METHODS: 129 SLE patients were studied regarding disease activity using SLEDAI (SLE Disease Activity Index) and cumulative damage using SLICC ACR (SLE International Collaborating Clinics/American College of Rheumatology Damage Index for SLE). At the same time, the β2M serum level, ESR (erythrocyte sedimentation rate), anti-dsDNA (anti-double-stranded DNA) and C3 and C4 complement fractions were determined. RESULTS: β2M levels correlated positively with SLEDAI (P = 0.02) and ESR (P = 0.0009) and negatively with C3 (P = 0.007). Patients who were positive for anti-dsDNA had higher β2M serum levels (P = 0.009). CONCLUSION: β2M levels are elevated in SLE patients with active disease. .

CONTEXTO E OBJETIVO: O lúpus eritematoso sistêmico (LES) é uma doença autoimune com curso clínico flutuante. Determinar a atividade clínica da doença é importante na escolha do tratamento correto. O objetivo deste estudo foi o de analisar se os níveis séricos de beta-2 microglobulina (β2M) têm valor na determinação da atividade clínica do LES. TIPO DE ESTUDO E LOCAL: Estudo transversal, analítico, realizado no ambulatório de reumatologia de um hospital universitário particular. MÉTODOS: 129 pacientes com LES foram estudados para atividade da doença pelo SLEDAI (SLE Disease Activity Index) e para dano cumulativo pelo SLICC (SLE International Collaborating Clinics/American College of Rheumatology Damage Index for SLE). Simultaneamente foram determinados os valores séricos de β2M, das frações C3 e C4 do complemento, VHS (velocidade de hemossedimentação) e anti dsDNA (DNA de dupla fita). RESULTADO: Encontrou-se correlação positiva entre níveis de β2M com o SLEDAI (P = 0,02), com VHS (P = 0,0009) e correlação negativa com níveis de C3 (P = 0,007). Pacientes com presença de anti dsDNA tinham níveis mais altos de β2M (P = 0,009). CONCLUSÃO: Níveis de β2M estão elevados em pacientes de LES com doença ativa. .

Acute inflammatory response to transgastric natural orifice transluminal endoscopic surgery peritoneoscopy: An experimental study in swine

OBJECTIVE: To investigate the impact of transgastric peritoneal access on plasma biomarkers of acute inflammatory response in comparison to laparoscopy. METHODS: This was a prospective and comparative study in a porcine model. Transgastric peritoneal access performed by natural orifice transluminal endoscopic surgery was compared with laparoscopy. Laparotomy and sham groups were used as positive and negative controls, respectively. Thirty-four pigs were assigned to receive transgastric natural orifice transluminal endoscopic surgery (n = 12), laparoscopy (n = 8), laparotomy (n = 8) or a sham procedure involving only anesthesia (n = 6). In the natural orifice transluminal endoscopic surgery group, peritoneoscopy was performed with a gastroscope via transgastric access. Blood samples were collected at baseline and 1, 3, 6, 9 and 24 h after the surgical procedure for measurement of interleukins 1β, 6 and 10 and tumor necrosis factor-α. A complete blood count was performed, and C-reactive protein levels were measured at baseline and at 24 h. RESULTS: All surgical and endoscopic procedures were performed without major complications. Peritoneal cavity inventory showed no signs of peritonitis in any animal. Interleukin 1β, interleukin 10 and tumor necrosis factor-α levels were below the threshold of detection. The mean level of interleukin 6 was statistically significantly higher in the laparotomy group than in the other groups (p<0.05), with no significant differences among the sham, laparoscopy and natural orifice transluminal endoscopic surgery groups (p>0.05). C-reactive protein analysis indicated significant increases in all groups, with no differences among the groups. Complete blood count analysis showed no differences among the groups. CONCLUSIONS: Based on the observed interleukin 6 patterns, the systemic inflammatory response resulting from transgastric ...

Impact of endoscopic sphincterotomy and bile duct exploration with open surgery on inflammatory response and immune function / 中华消化内镜杂志

Objective To evaluate the impact of endoscopic sphincterotomy (EST) and bile duct exploration with open surgery on immune function and inflammatory response.Methods Fifty-one patients with choledocholithiasis were divided into endoscopy group ( EG,n =24) and laparotomy group ( LG,n =27 ) according to the patients' will from June 2010 to February 2012.Procalcitonin( PCT),C-reactive protein (CRP),immunoglobulins (IgA 、lgG 、IgM ) and T lymphocyte (CD4、CD8 ) of peripheral blood were examined preoperatively and on the 1st,3rd and 5th day postoperatively.Results Compared with preoperative levels,postoperative levels of serum PCT and CRP were higher in both groups (P ＜0.01 ),but on the 3rd day after the operation,the changes of PCT and CRP levels in the two groups were not significantly different ( P ＞ 0.05 ).Postoperative levels of serum immunoglobulins of two groups were lower than preoperative levels (P ＜ 0.01 ),but the IgA and IgM levels in EG were significantly higher than those in the LG (P ＜ 0.05),and IgG levels in the two groups were not significantly different after surgery ( P ＞ 0.05 ).Compared with preoperative levels,postoperative levels of CD4,CD8 and CD4/CD8 ratio in EG were only slightly decreased (P ＞ 0.05 ),and returned to the preoperative levels on the 5th day postoperatively,but postoperative levels of these variables in LG were decreased significantly ( P ＜ 0.05).Postoperative levels of CD4,CD8 and CD4/CD8 ration of the two groups were significantly different (P ＜ 0.05).Conclusion Both EST and bile duct exploration with open surgery can inhibit immune function and induce inflammation,but the procedure of EST,which may mainly affect humoral immune function,has impact on immune function less intensely.

Could Prior Oral-bisphosphonate Administration Reduce the Acute Phase Reaction of Zoledronate?

OBJECTIVE: Bisphosphonates are the most commonly prescribed medications for the treatment of osteoporosis. This study was designed to analyze the rate of acute phase reaction (APR) following Zoledronate 5 mg administration in patients with osteoporosis who were treated with prior oral bisphosphonate for at least 2 weeks and to compare naive IV 5 mg Zoledronate. METHODS: Between July 2009 and October 2010, 27 patients with osteoporosis who were treated with prior oral bisphosphonate for at least 2 weeks, and maximum 52 weeks (average 18.5 weeks) and were between 42-and 85-year-old at the time of study participation. We prospectively evaluated APR, including fever, flu-like symptoms, headache, arthralgia, and myalgia, after 5 mg zoledronate by questionnaire. Additionally we assessed a visual analogue scale (VAS) by 4-point categorical scale. RESULTS: In this study of 27 patients with osteoporosis, the frequency of APR, flu-like symptom and myalgia were 14.8% and 7.4% and fever, arthralgia, and headache were 3.7% respectively. In VAS, all reactions were mild. The rate of APR rate in this study was statistically decreased compared to previous reports with zoledronate 5 mg IV in bisphosphonate-naive patients. CONCLUSION: Prior oral bisphosphonate administration for at least 2 weeks could significantly reduce the APR of IV zoledronate 5 mg.

Changes in cortisol secretion in the acute phase of traumatic brain injury / 中华麻醉学杂志

Objective To investigate the changes in cortisol (COR) secretion in the acute phase of traumatic brain injury (TBI) .Method Seventy-five patients admitted to the hospital at 2-24 h after TBI were divided into 3 groups based on the Glasgow Coma Scale score: mild TBI group (group TBI1, n = 30), moderate TBI group (group TBI2, n = 12) and severe TBI group (TBI3, n = 33). Thirteen patients with cervical spondylosis or osteoma of the skull (admitted to the hospital at the same period) were regarded as control group (group C). Venous blood samples were taken on the first day after admission to measure the serum concentrations of total COR, adrenocorticotropin (ACTH) and corticosteroid-binding globulin (CBG). Free COR concentrations and free COR index were calculated. High blood COR was recorded. Result Compared with group C, the serum concentrations of total COR and ACTH, free COR levels and free COR index were significantly increased in TBI1, TBI2 and TBI3groups (P ＜ 0.05). The parameters mentioned above were significantly higher in TBI2 and TBI3 groups than in TBI1 group ( P ＜0.05). There was no significant difference in serum CBG concentrations among the four groups.The incidence of high blood COR was significantly higher in TBI1, TBI2 and TBI3 groups than in C group, and in TBI3 group thanin TBI1 and TBI2 groups (P ＜0.05). Conclusion COR secretion is increased in the acute phase of TBI and the level of COR secretion is related to the severity of brain damage.

Resposta inflamatória na circulação extracorpórea: estratégias terapêuticas / Inflammatory response to extracorporeal circulation: therapeutic strategies

O by-pass cardiopulmonar substitui temporariamente as funções do coração e pulmões durante a realização de cirurgias cardíacas. A exposição dos componentes sanguíneos à superfície não endotelial do circuito de circulação extracorpórea (CEC) constitui-se no principal responsável pela ativação da resposta inflamatória. Acredita-se que fatores humorais e celulares, incluindo citocinas pró-inflamatórias, sejam ativados durante o by-pass cardiopulmonar. As manifestações clínicas da síndrome de resposta inflamatória sistêmica (SIRS) incluem alterações cardíacas, respiratórias, renais, hepáticas e neurológicas, diátese hemorrágica e, eventualmente, falência orgânica múltipla. Diversas estratégias têm sido propostas para tratamento da SIRS, entre elas a administração de fármacos, modificações na técnica cirúrgica e otimização da técnica de perfusão.

Cardiopulmonary by-pass temporarily replaces the functions of the heart and lungs during cardiac surgery. The exposure of blood components to extra-corporeal circuit (ECC) synthetic surfaces is the mainly responsible for the inflammatory response activation. It is currently believed that cellular and humoral factors, including pro-inflammatory cytokines, may be activated during cardiopulmonary bypass. The clinical manifestations ofthe systemic inflammatory response syndrome (SIRS) include cardiac, respiratory, renal, hepatic, and neurological dysfunction, bleeding diathesis, and even multiple-system organ failure. Among the therapeutic maneuvers proposed to mitigate the consequences of SIRS include the administration of drugs, surgical techniques modifications and perfusionpractice optimization.

Fase aguda da infecção por toxoplasma gondii: avaliação do parasitismo sanguíneo e resposta humoral em camundongos isogênicos AS/n / Toxoplasma gondii acute infection: estimation of humoral response andblood parasitism in mice AS/n inbred

Objetivos: analisar experimentalmente a evolução da resposta imune humoral nas fases aguda e crônica recente da infecção por Toxoplasma gondii e sua correlação com o parasitismo sanguíneo. Métodos: foram analisados, por 60 dias, 10 camundongos fêmeas da linhagem AS/n infectados, por via oral, com 10 cistos por animal da cepa ME-49 de Toxoplasma gondii. As coletas de sangue foram feitas a cada 3-4 dias. O parasitismo sanguíneo foi avaliado pela reação em cadeia da polimerase e os títulos de anticorpos por enzimaimunoensaio e imunofluorescência indireta. Resultados: a reação em cadeia da polimerase foi positiva em amostras com intervalos de aproximadamente 7 dias até o 28º dia, e a seguir, negativas até o 60º dia. Os soros avaliados pela imunofluorescência indireta apresentaram anticorpos IgM após o 7º dia, com pico entre o 18º e 27º dia. Após o primeiro mês os títulos foram baixos até o 60º dia. Anticorpos IgG surgiram no 14º dia e persistiram em altos títulos até o 60º dia. A cinética dos anticorpos IgG, bem como a avidez destes, demonstrou que os níveis de anticorpos aumentaram a partir do 14º dia e as porcen-tagens de avidez evoluíram com pico máximo após 28 dias, estabelecendo-se então a fase crônica da infecção. Conclusões: os dados aqui demonstrados enfatizam que taquizoítos podem estar presentes na circulação sanguínea durante toda a fase aguda da toxoplasmose, mesmo que já se tenha instalado a resposta imune protetora.

Aims: To analyze experimentally the humoral immune response in acute and recent chronic infections by Toxoplasma gondii and its correlation with the blood parasitism. Methods: Ten female mice AS/n inbred strain orally infected with 10 cysts per animal from T. gondii ME-49 strain were evaluated during 60 days. Blood collections were made in each 3-4 days. Blood parasitism was evaluated by polymerase chain reaction, and antibody titres by enzyme-linked immunosorbent assay and indirect immunofluorescence. Results: Positive polymerase chain reaction was detected around seven day-intervals until the 28th day and was negative after the 30th day pos-infection. Sera assayed by immunofluorescence presented IgM antibodies after the 7th day of infection and high titers were found between the 18th and 27th day. After 30 days, IgM titers were low until the 60th day. IgG antibodies were produced around the 14th day and were high until the 60th day. The avidity and kinetic exhibited by IgG antibody levels increased from the 14th day and the avidity percents increased with maximum peak after 28 days, establishing the chronic infection. Conclusions: These data emphasize that tachyzoites can be detected in blood during the acute phase of toxoplasmosis, even though the protective immune response was already developed.

Acute Effects of Intravenous Administration of Pamidronate in Patients with Osteoporosis

We investigated acute effects of intermittent large dose bisphophonate therapy in osteoporotic patients. Peripheral blood mononuclear cells were incubated with alendronate (100 micrometer) for 18 hr, in vitro and cytokine expressions were measured by real-time RT-PCR. Pamidronate 30 mg was administered on 26 osteoporotic patients; and acute phase reactants, inflammatory cytokines and bone biomarkers were measured. The in vitro study showed significant increase in mRNA expression of IL-6, TNF-alpha and IFN-gamma. A notable rise in serum C-reactive protein (CRP) was observed over 3 days after pamidronate infusion (P=0.026). Serum levels of TNF-alpha, IL-6 and IFN-gamma were also significantly increased (P=0.009, 0.014, 0.035, respectively) and the increase in IL-6 levels were strongly correlated with CRP levels (P=0.04). Serum calcium and c-telopeptide levels rapidly decreased after the treatment (P=0.02, <0.001, respectively). This study showed that mRNA expression of inflammatory cytokines at peripheral blood mononuclear cells (PBMC) level were observed within 18 hr and marked elevation of inflammatory cytokines and acute phase reactants were demonstrated after pamidronate infusion at the dose for osteoporosis. Our studies confirmed that intermittent large dose aminobisphosphonate causes acute inflammation.

The variety of the neutrophil volume and cytoplasm-nucleus complex and their significance in acute bacterial infection and stringency diseases / 中华检验医学杂志

Objective To investigate the variety and clinical value of the neutrophil volume and cytoplasm-nucleus complex in patients with bacterial infection, cardiovascular or cerebrovascular accident and major surgery operation. Methods 125 patients with bacterial infection, 64 patients with acute cardiovascular or cerebrovascular accident, 66 patients after major surgery operation and 69 normal subjects were selected in the study. Total WBC counts (WBC), percentage of neutrophils (NE), and the VCS parameters of neutrephils including the mean channels of cell volume ( NEV), conductivity ( NEC), light scatter(NES) and the SD of these parameters( NEVSD, NECSD, NESSD)were measured by automatic blood cell analyzing instrument. The sensitivity and specificity of the WBC, NE and the VCS parameters of neutrophils were analyzed with receive operating characteristic (ROC) curve. Results The levels of NEV, NES and NEVSD in acute bacterial infection group were 154.3 ± 15.2, 135.7 ± 9.9, 26.8 ± 4.2 respectively. The levels of NEV, NES and NEVSD in post major surgery operation group were 147.2±8.9, 141.5 ± 7.7, 23.0 ± 2. 8 respectively. The levels of NEV, NES and NEVSD in acute cardiovascular or cerebruvascular accident group were 144.9 ± 5. 2, 146.0 ±5.0, 19. 6±1.6 respectively. The levels of NEV, NES and NEVSD in healthy control group were 139.7±4.6, 145.0±3.8, 18.2±1.3 respectively. The differences of these parameters among these groups had statistical significance ( F = 17. 650, 38. 122, 54. 604,P<0. 05). And the changes of NEV, NES and NEVSD in bacterial infection group were most obvious among those three groups. The levels of NEV, NES and NEVSD were 146.5±9.5, 144.3 ± 9.4, 21.3 ± 3.3 respectively in stress diseases groups which included acute cardiovascular or cerebrovascular accident group and post major surgery operation group. The differences of these parameters between stress diseases group and acute bacterial infection group had statistical significance ( t = - 2.840, 7.533, - 8.999,P<0.01). The areas under the ROC curve of NEVSD, NEC, NES and NECSD were 0.893, 0. 845, 0. 833 and 0. 849 respectively. The sensitivity of 83. 3% and specificity of 82. 0% could be achieved by selecting the cut-off equal to or greater than 24. 0. Conclusions The variety of neutrophil volume, nuclear size and cytoplasmic granularity changed obviously in patients with acute bacterial infection and common stress diseases, and the variety in acute bacterial infection is more obvious than that in common stress diseases. The sensitivity and specificity of VCS parameters of neutrophils are higher than those of WBC or NE for predicting infection, and the NEVSD is the most predictable indicator of acute bacterial infection.