Zarzio Ameliorates Non-alcoholic Fatty Liver Induced By a High Fat Diet in a Rat Experimental Model: A Histological and Immunohistochemical Study

SUMMARY: The therapeutic effect of a granulocyte-colony stimulating factor (G-CSF) biosimilar drug, zarzio, on non-alcoholic fatty liver disease (NAFLD) in a rat model was investigated in this study. Thirty-two rats were randomly divided into four groups. Groups I and II were fed a standard laboratory diet, whereas groups III and IV were fed a high fat diet (HFD) for 14 weeks. After 12 weeks of feeding, groups I and III were administered normal saline, and groups II and IV were intraperitoneally administered zarzio (200 mg/kg/day) for two consecutive weeks. Hematoxylin-eosin (H&E) staining was used to assess hepatic and pancreatic morphology in all groups, oil red O (ORO) staining for lipid accumulation, Masson's staining for fibrosis, and immunohistochemistry assay for hepatic protein expression of insulin receptor substrate 1 (IRS1), nuclear factor erythroid 2-related factor 2 (Nrf2), tumour necrosis factor alpha (TNF-α) and pancreatic caspase-3. The NAFLD rats (group III) developed hepatic steatosis with increased lipid accumulation, perisinusoidal fibrosis, upregulated IRS1, TNF-α (all P<0.05) without a significant increase in Nrf2 protein expression compared with normal control. In comparison, model rats treated with zarzio (group IV) showed significant rejuvenation of the hepatic architecture, reduction of fat accumulation, and fibrosis. This was accompanied by the upregulation of Nrf2, downregulation of IRS1 and TNF-α protein expression (all P<0.05). No correlation was detected between NAFLD and non-alcoholic fatty pancreas disease (NAFPD). However, the pancreatic β-cells in group III showed increased caspase-3 expression, which was decreased (P<0.05) in group IV. In conclusion, zarzio ameliorates NAFLD by improving the antioxidant capacity of liver cells, reducing hepatic IRS1, TNF-α protein expression and pancreatic β-cells apoptosis, suggesting that zarzio could be used as a potential therapy for NAFLD.

En este estudio se investigó el efecto terapéutico de un fármaco biosimilar del factor estimulante de colonias de granulocitos (G-CSF), zarzio, sobre la enfermedaddel hígado graso no alcohólico (NAFLD) en un modelo de rata. Treinta y dos ratas se dividieron aleatoriamente en cuatro grupos. Los grupos I y II fueron alimentados con una dieta estándar de laboratorio, mientras que los grupos III y IV fueron alimentados con una dieta alta en grasas (HFD) durante 14 semanas. Después de 12 semanas de alimentación, a los grupos I y III se les administró solución salina normal, y a los grupos II y IV se les administró zarzio por vía intraperitoneal (200 mg/kg/ día) durante dos semanas consecutivas. Se utilizó tinción de hematoxilina-eosina (H&E) para evaluar la morfología hepática y pancreática en todos los grupos, tinción con rojo aceite O (ORO) para la acumulación de lípidos, tinción de Masson para la fibrosis y ensayo de inmunohistoquímica para la expresión de la proteína hepática del sustrato 1 del receptor de insulina (IRS1), factor nuclear eritroide 2 relacionado con el factor 2 (Nrf2), factor de necrosis tumoral alfa (TNF-α) y caspasa-3 pancreática. Las ratas NAFLD (grupo III) desarrollaron esteatosis hepática con aumento de la acumulación de lípidos, fibrosis perisinusoidal, IRS1 y TNF-α regulados positivamente (todos P <0,05) sin un aumento significativo en la expresión de la proteína Nrf2 en comparación con el control normal. En comparación, las ratas modelo tratadas con zarzio (grupo IV) mostraron un rejuvenecimiento significativo de la arquitectura hepática, una reducción de la acumulación de grasa y fibrosis. Esto estuvo acompañado por la regulación positiva de Nrf2, la regulación negativa de la expresión de la proteína IRS1 y TNF-α (todas P <0,05). No se detectó correlación entre NAFLD y la enfermedad del páncreas graso no alcohólico (NAFPD). Sin embargo, las células β pancreáticas en el grupo III mostraron una mayor expresión de caspasa-3, que disminuyó (P <0,05) en el grupo IV. En conclusión, zarzio mejora la NAFLD al mejorar la capacidad antioxidante de las células hepáticas, reduciendo el IRS1 hepático, la expresión de la proteína TNF-α y la apoptosis de las células β pancreáticas, lo que sugiere que zarzio podría usarse como una terapia potencial para la NAFLD.

Herbal Medicine from Single Clove Garlic Oil Extract Ameliorates Hepatic Steatosis and Oxidative Status in High Fat Diet Mice

@#Introduction: High fat diet (HFD) can cause lipid accumulation and contribute to various metabolic disorders. Single clove garlic oil (SCGO) has advantages over regular garlic due to its higher amounts of organosulfide compounds in particular. This study aimed to determine the ability of SCGO extract to ameliorate hepatic steatosis and improve oxidative status by modulating expression of tumour necrosis factor α and superoxide dismutase in mice fed a HFD. Methods: Twenty-four adult male Balb/C mice were divided into six groups: i) normal diet; ii) positive control diet; iii) negative control diet; and iv) HFD with SCGO at 12.5 mg/kg body weight (mg/kg BW); v) HFD with SCGO at 25 mg/kg BW, vi) HFD with SCGO at 50 mg/kg BW. Liver weight and morphology, spleen weight, serum levels of superoxide dismutase (SOD) and tumour necrosis factor α (TNF-α), TNF-α expression in the aorta and lipid profiles were assessed at the end of the experimental period. Results: SCGO treatment was associated with significant decreases in liver and spleen weight as well as amelioration of hepatic steatosis. SCGO treatment also decreased TNF-α levels and expression. Serum levels of SOD in the SCGO groups were significantly increased compared with the negative control group. Lipid profiles were improved in the SCGO treatment groups compared with the negative control group. Conclusion: SCGO as an herbal medicine could be an effective treatment for degenerative disorders caused by HFD.

Correlation of Small Dense Low Density Lipoprotein, Tumour Necrosis Factor - alpha with Liver Enzymes in Chronic Hepatitis B Patients

Aim:This study investigated the relationship between small dense low density lipoprotein (sdLDL), tumour necrosis factor-alpha (TNF-α), aspartate aminotransferase (AST), alanine aminotransferase(ALT) and alkaline phosphatase (ALP) in chronic hepatitis B patients.Duration of Study: June2018-March 2019.Subjects and Methods:Sixty (60) participants were recruited for this cross sectional study. They comprised thirty (30) clinically diagnosed chronic hepatitis B virus (HBV) infected patients attending clinic at a tertiary hospital in Osogbo, Osun state, Nigeria. Thirty (30) apparently healthy volunteers were recruited as control subjects after fulfilling the inclusion criteria. Anthropometric measurements were performed using standard method. About 6mL of venous blood was collected from each study participant,serum was extracted and kept at -80oC until time of analysis. Small dense LDL, TNF-α, AST, ALT and ALP were determined using enzymelinked immunosorbent assay and colorimetric method as appropriate. Data analysis was doneusing Student’s t-test for Original ResearchArticle comparison of variables and Pearson’s correlation was used to determine the relationship between variables. P–value less than 0.05 was considered significant. Results:SdLDL, TNF-α, AST and ALT were significantly elevated in HBV patients when compared with the control subjects (P<0.05). SdLDL had a significant positive correlation with TNF-α (P=0.03), AST (P=0.01), ALT (P=0.00). TNF-α had a significant positive correlation with AST (P=0.02) and ALT (P=0.00).Conclusion:This study revealed a noteworthy positive relationship between sdLDL, TNF-α and hepatic aminotransferases in chronic hepatitis B patients

Effects of blood glucose fluctuation on the expression of TLR4 and TNF-α in the liver of diabetic rats / 预防医学

Objective@# To investigate the effect of blood glucose fluctuation on the expression of toll-like receptor 4（TLR4）and tumour necrosis factor-α（TNF-α）in the liver of diabetic rats .@*Methods @#The adult male Sprague-Dawley（SD）rats were used to establish diabetic rats model and then they were randomly assigned to sustained hyperglycemia group（MS group,n=20） and fluctuating hyperglycemia group（MF group,n=20）. The two groups continued high-fat and high-sugar diet,while MF group alternately received intraperitoneal injection of glucose and subcutaneous injection of short-acting insulin. Another 10 SD rats were assigned to the control group. After 6 weeks,the physical signs,blood glucose,triglyceride（TG）,total cholesterol（TC）,low density lipoprotein cholesterol（LDL-C）,high density lipoprotein cholesterol（HDL-C）,alanine aminotransferase（ALT）and aspartate aminotransferase（AST）of the rats were measured;the mRNA expression of TLR4 and TNF-α in liver tissues were detected by reverse transcription-polymerase chain reaction （RT-PCR）;pathological changes of liver tissues were observed after HE staining .@*Results @#Compared with the control group,the rats in the MS group were always at the hyperglycemia status,the blood glucose of the rats in the MF group drifted between the peak and the trough. The weight growth of the rats in the MS group and MF group were slower. The levels of TC,TG and LDL-C significantly increased and the level of HDL-C significantly decreased in the MS group and MF group （all P<0.05）. The activities of ALT and AST increased both in the MS group and MF group,with the MF group increased more significantly（P<0.05）. The mRNA expression levels of TLR4 and TNF-α in liver tissues of the rats in MS group and MF group increased,with the MF group increased more significantly（P<0.05）. HE staining results showed that the liver cells of the rats in the MF group had more lipid droplet deposition,with the disordered hepatocyte line arrangement and more severe lipid droplet vacuolation. The lesion rate of the MS group and MF group were 83.30% and 100.00% .@*Conclusion@# The rats in this model showed signs of hyperglycemia complicated by dyslipidemia and liver injury. The expression of TLR4 and TNF-α increased in rats with blood glucose fluctuation,which might play a role in the aggravation of diabetic liver injury.

Investigation of the risk of hepatitis B virus reactivation in arthritis patients undergoing anti-tumour necrosis factor alpha therapy / 中华内科杂志

Objective To investigate the prevalence of HBV infection and the risk of hepatitis B virus (HBV) reactivation in patients with inflammatory arthritis receiving tumour hecrosis factor alpha (TNFα) inhibitors.Methods The liver function,serology of HBV and viral loads (HBV DNA) were tested before using TNFα inhibitors,at 3 months and 6 months.Patients with chronic hepatitis B (CHB) infection (HBV DNA ＞ 1 × 103copies/ml) were eliminated.Results A total of 162 patients were investigated including 156 patients who finished the study.Eleven (7.05％) patients were HBsAg-positive.Two patients with HBV DNA ＞ 1 × 103copies/ml were eliminated before starting anti-TNFα therapy.Among HBsAgpositive patients,HBV reactivation was documented in only one of the 11 patients.This patient with rheumatoid arthritis developed elevation of glutamic-pyruvic transaminase (ALT) and HBV DNA copies three months after infliximab therapy.Therefore lamivudine was given for three months,which translated into the fall of ALT and HBV DNA copies back to normal level.After follow-up for six months,the virology and serology remained stable.In contrast,none of the other 155 patients had demonstrated evidence of HBV infection or HBV reactivation.Conclusion The kinetics of HBV viral loads should be carefully monitored in patients with inflammatory arthritis and HBsAg-positive during anti-TNFα therapy.HBV reactivation should be treated with antiviral medicine through out the period of anti-TNFα therapy.

Pneumonia por Legionella após uso de Infliximabe em paciente com Artrite Reumatoide / Legionella pneumonia after infliximab in a patient with Rheumatoid Arthritis

Os antagonistas do fator de necrose tumoral (anti-TNF) têm sido utilizados com sucesso em várias doenças inflamatórias crônicas, como artrite reumatoide (AR), mas alguns estudos observaram a ocorrência de infecções por patógenos intracelulares em pacientes medicados com anti-TNF. Relatamos um caso de paciente mulher com diagnóstico prévio de AR durante 16 anos e que estava sendo medicada com várias drogas antirreumáticas modificadoras de doença (DARMDs), tendo como resultado o insucesso terapêutico, sendo em seguida tratada com infliximab. Depois de transcorridos 15 dias da segunda dose, a paciente foi acome- tida por dor torácica ventilatório-dependente, tosse seca e dispneia. Foi hospitalizada, e o diagnóstico de pneumonia por Legionella pneumophila foi confirmado pela presença do antí- geno de Legionella na urina. TNF é uma citocina inflamatória que também promove inibição do crescimento bacteriano de patógenos intracelulares, e sua inibição parece aumentar a sensibilidade a essas infecções em alguns pacientes.

The antagonists of tumour necrosis factor (anti-TNF) have been successfully used in several chronic inflammatory diseases such as Rheumatoid Arthritis (RA), but some studies have observed the development of infections by intracellular pathogens in patients using anti-TNF. We report a case of a female patient with previous diagnosis of RA for 16 years that used several disease-modifying anti-rheumatic drugs (DMARDs) that resulted in treatment failure, and then was treated with infliximab. After fifteen days of the second dose, the patient developed ventilatory-dependent chest pain, dry cough and dyspnea. She was hospitalized, and the diagnosis of pneumonia by Legionella pneumophila was confirmed by the presence of Legionella antigen in an urine test. TNF is an inflammatory cytokine that also acts inhibiting the bacterial growth of intracellular pathogens, and its inhibition seems to increase susceptibility to these infections in some patients.

Efecto del ejercicio cardiovascular en las mujeres con obesidad sobre las concentraciones de la adiponectina, leptina y factor de necrosis tumoral-alfa / Cardiovascular exercise on obese women: Effects on adiponectine, leptine, and tumour necrosis factor-alpha

Introducción: La relación de las hormonas adiponectina, leptina y factor de necrosis tumoral-alfa del tejido adiposo sobre el proceso aterogénico es uno de los modelos más prometedores en la medicina preventiva. Los numerosos ensayos realizados para identificar el efecto del ejercicio sobre estas hormonas no han sido claros en el tipo de rutina de ejercicio y esfuerzo físico calculado que contribuya al cambio de las concentraciones plasmática en mujeres con obesidad. Objetivo: Analizar el efecto del ejercicio cardiovascular controlado sobre los niveles séricos de la adiponectina, la leptina y el factor de necrosis tumoral-alfa en mujeres jóvenes con obesidad. Método: Ensayo clínico simple ciego. La intervención consistió en un programa de ejercicio cardiovascular controlado durante 10 semanas en 34 mujeres (casos n = 17; controles n = 17), con un índice de masa corporal > 27 kg/m². Se realizó análisis molecular por inmunofluorescencia. Resultados: Posterior a la intervención, las medias de los casos y controles fueron las siguientes: adiponectina 19 vs. 12.2 μ/ml (p = 0.008); leptina 20 vs. 28 μ/L (p = 0.02) y factor de necrosis tumoral-alfa 4.7 vs. 5.1 pg/ml (p = 0.05). Conclusiones: La rutina de ejercicio establecida (5 sesiones a la semana de ejercicio de 40 min cada una durante 10 semanas con una frecuencia cardiaca de reserva del 40 al 80%) mejoró las concentraciones plasmáticas de las hormonas en la dirección esperada. Este hallazgo destaca una rutina inédita de ejercicio, controlada por frecuencia cardiaca de reserva que podría contribuir a la protección cardiovascular y metabólica en mujeres jóvenes obesas.

Introduction: The relationship of hormones adiponectin, leptin and tumor necrosis factor-alpha in adipose tissue on the atherogenic process is one of the most promising models in preventive medicine. The numerous tests performed to identify the effect of exercise on these hormones have not been clear on the type of exercise routine and physical effort calculated to contribute to changing plasma concentrations in obese women. Objective: Analyze controlledcardiovascular exercise effect on serum level of adiponectin, leptin, and tumournecrosis factor-alpha in obese young women. Method: A simple blind clinical essay. The intervention covered a 10-week controlled, cardiovascular exercise program by 34 women (cases n = 17, controls n = 17) with a body mass index > 27 kg/m². Molecular analysis was performed by immune-fluorescence. Results: Following the intervention, cases and controls means were as follows: adiponectin 19.0 vs. 12.2 μ/ml (P = .008); leptin 20.0 vs. 28.0 μ/L (P = .02); and tumour necrosis factor-alpha 4.7 vs. 5.1 pg/ml (P = .05). Conclusions: The established exercise (5 sessions a week of exercise of 40 min each for 10 weeks with a heart rate reserve of 40 to 80%) improved plasma concentrations of these hormones in the expected direction. This finding highlights an unpublished amount of exercise, controlled by the reserve cardiac frequency that might contribute the cardiovascular and metabolic protection to obese women.

Therapeutic Effect of Curcumin Supplementation in the Modulation of NF-κB Responsive Genes in a Collagen-induced Arthritis Rat Model.

Aims: To assess the therapeutic effect of curcumin supplementation in modulating the expression of NF-κB in the joints of collagen-induced arthritis (CIA) rats. Place and Duration of Study: Department of Postgraduate Studies and Research, International Medical University, between July 2011 and May 2012. Methodology: Arthritis was induced in each group of Dark Agouti (DA) rats, by intradermal injection with collagen emulsified in complete Freund’s adjuvant. Treatment groups which were induced with CIA were treated with: 500 mg/kg curcumin; 1000 mg/kg curcumin; 2000 mg/kg curcumin; 25 mg/kg aspirin. Combination treatment groups which were induced with CIA were treated with: 500 mg/kg curcumin and 25 mg/kg aspirin; 1000 mg/kg curcumin and 25 mg/kg aspirin; 2000 mg/kg curcumin and 25 mg/kg aspirin from day 25 to 38. Efficacy was assessed based on ability to reduce paw oedema, histopathological changes, NF-κB expression, serum tumour necrosis factor alpha (TNF- α), interleukin 1-beta (IL-1β) and gluthathione peroxidase (GPx) levels. Results: Based on histopathological study, immunohistochemical scoring of NF-κB and ELISA analysis of TNF-α, IL-1β and GPx levels, our study found that curcumin given after arthritis in high doses, shows effects of healing and this results were comparable to positive control group, which is the arthritic group treated with 25 mg/kg aspirin. Curcumin given in combination with aspirin, showed better reduction in pathology in arthritic group compared to positive control group, especially with higher doses of curcumin. Conclusion: Curcumin was effective in reducing inflammatory changes seen in CIA joints which were proved through histopathological, immunohistochemical and biochemical analysis, however only at high doses.

Effect of Extracorporeal Shock Wave on Expression of Interleukin-1β and Tumour Necrosis Factor-α in Cartilage in Rabbits with Knee Osteoarthritis / 中国康复理论与实践

@#Objective To explore the effect of extracorporeal shock wave (ESW) on expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in cartilage in rabbits with knee osteoarthritis. Methods 30 rabbits were randomly divided into control group, model group and treatment group, with 10 rabbits in each group. Model of knee osteoarthritis was established with modified plaster cast in extension position for 6 weeks except the control group, and the treatment group was treated with ESW (each 1000 impulse, the energy flux density of 0.1 mJ/mm2). The rabbits were sacrificed respectively 4 weeks after ESW treatment, the general and histological changes of articular cartilage were examined and immunohistochemical staining was used to observe the expression of IL-1β and TNF-α in cartilage. Results The expression of IL-1β and TNF-α were significantly lower in the treatment group than in the model group (P<0.01). Conclusion ESW can down-regulate the expression of IL-1β and TNF-α in chondrocytes with osteoarthritis.

Comparative analysis of adverse events between infliximab and adalimumab in Crohn's disease management: a Brazilian single-centre experience / Análise comparativa dos eventos adversos entre infliximabe e adalimumabe no tratamento da doença de Crohn: experiência em um centro brasileiro

INTRODUCTION: Data is scarce regarding adverse events (AE) of biological therapy used in the management of Crohn's Disease (CD) among Brazilian patients. OBJECTIVES: To analyse AE prevalence and profile in patients with CD treated with Infliximab (IFX) or Adalimumab (ADA) and to verify whether there are differences between the two drugs. METHOD: Retrospective observational single-centre study of CD patients on biological therapy. Variables analysed: Demographic data, Montreal classification, biological agent administered, treatment duration, presence and type of AE and the need for treatment interruption. RESULTS: Forty-nine patients were analysed, 25 treated with ADA and 24 with IFX. The groups were homogeneous in relation to the variables studied. The average follow-up period for the group treated with ADA was 19.3 months and 21.8 months for the IFX group (p = 0.585). Overall, 40% (n = 10) of patients taking ADA had AE compared with 50% (n = 12) of IFX users (p = 0.571). There was a tendency towards higher incidence of cutaneous and infusion reactions in the IFX group and higher incidence of infections in the ADA treated group, although without significant difference. CONCLUSIONS: No difference was found in the AE prevalence and profile between ADA and IFX CD patients in the population studied. (AU)

INTRODUÇÃO: Há poucos dados sobre os eventos adversos (EA) da terapia biológica usada no tratamento da doença de Crohn (DC) entre os pacientes brasileiros. OBJETIVOS: Analisar a prevalência dos EA e o perfil dos pacientes com DC tratados com Infliximabe (IFX) ou Adalimumabe (ADA) e verificar se há diferenças entre esses dois fármacos. MÉTODO: Estudo observacional e retrospectivo de pacientes com DC em terapia biológica, realizado em centro único. As variáveis analisadas foram: dados demográficos, classificação de Montreal, agente biológico administrado, duração do tratamento, presença e tipo de EA e necessidade de interrupção do tratamento. RESULTADOS: Quarenta e nove pacientes foram analisados, 25 tratados com ADA e 24 com IFX. Os grupos eram homogêneos em relação às variáveis estudadas. O período médio de acompanhamento foi de 19,3 meses para o grupo tratado com ADA e de 21,8 meses para o grupo tratado com IFX (p = 0,585). No total, 40% dos pacientes (n = 10) que receberam ADA tiveram AE, em comparação com 50% dos pacientes (n = 12) que receberam IFX (p = 0,571). Houve uma maior incidência de reação cutânea e à infusão no grupo IFX e de infecções no grupo ADA, embora sem diferença significativa. CONCLUSÃO: Não houve diferença na prevalência de EA e no perfil dos pacientes com DC que receberam ADA e IFX. (AU)

Avaliação do peso corporal em pacientes com doença de Graves durante o tratamento com metimazol / Evaluation of body weight in patients with Graves' disease during the treatment with methimazole

OBJETIVO: Avaliar a alteração de peso durante o tratamento do hipertiroidismo e correlacioná-la com IL-6 e TNF-alfa. SUJEITOS E MÉTODOS: Quarenta e dois pacientes foram incluídos. Peso corporal (PC), índice de massa corpórea (IMC), características clínicas e laboratoriais foram registrados. IL-6 e TNF-alfa foram determinados antes do tratamento com metimazol (MMI) e no estado de eutiroidismo. RESULTADOS: O PC foi de 59,62 ± 11,5 kg no estado de hipertiroidismo e de 69,91 ± 14,4 kg no estado de eutiroidismo (p < 0,001). O IMC aumentou de 23,1 ± 3,8 kg/m² para 27 ± 4,7 kg/m² durante o tratamento (p < 0,0001). Antes da terapia, 66,6% tinham IMC < 25 kg/m² e 33,3%, IMC > 25 kg/m². No estado de eutiroidismo, 38% dos pacientes apresentavam IMC < 25 kg/m² e 62%, IMC > 25 kg/m² (p = 0,01). No estado de eutiroidismo, encontrou-se significativa diminuição nos valores de IL-6 e TNF-alfa, mas nenhuma correlação entre IL-6 e TNF-alfa com PC ou IMC. CONCLUSÃO: Um importante aumento no PC e IMC foi observado durante o tratamento do hipertiroidismo e alterações de IL-6 e TNF-alfa relacionam-se somente com o retorno ao eutiroidismo.

OBJECTIVE: To evaluate weight change during hyperthyroidism treatment, and to correlate it with IL-6 and TNF-alpha concentrations. SUBJECTS AND METHODS: Forty two patients were included. Body weight (BW), body mass index (BMI), clinical and laboratory characteristics were recorded. IL-6 and TNF-alpha were determined before treatment with methimazole (MMI) and in euthyroidism. RESULTS: BW was 59.62 ± 11.5 kg in hyperthyroidism, and 69.91 ± 14.4 kg in euthyroidism (p < 0.001). BMI increased from 23.1 ± 3.8 kg/m² to 27 kg/m² ± 4.7 during treatment (p < 0.0001). Before treatment, 66.6% subjects had BMI < 25 kg/m² and 33.3%, BMI > 25 kg/m². In euthyroidism, 38% of patients had BMI < 25 kg/m² and 62%, BMI > 25 kg/m² (p = 0.01). In euthyroidism, we found a significant reduction in IL-6 and TNF-alpha concentrations, but no correlation between IL-6 and TNF-alpha, and BW or BMI. CONCLUSION: An important increase in BW and BMI was observed during hyperthyroidism treatment, and IL-6 and TNF-alpha alterations were only related with return to euthyroidism.

Moderate regular exercises reduce inflammatory response for physical stress.

Exercises induce pro-inflammatory cytokines. We assessed the effect of different grades of exercises on inflammatory cytokine response. Twenty healthy volunteers performed a single bout of moderate exercise, a single bout of strenuous exercise and one month regular moderate exercise using standardized 10m Shuttle Walk Test. Interleukin-6 (IL-6) and Tumour Necrosis Factor Alpha (TNF-∝) were estimated by Sandwich ELISA method after each exercise regime. Statistics were run using SPSS software version 11.0, Systat software. Repeated measures ANOVA has been used for analysis of IL-6 values and Friedman test has been used for analyzing TNF-∝ and IL-6 values. Twenty healthy volunteers (18 to 30 years) were chosen for this study. The mean and SEM of plasma levels (pg/ ml) of IL-6 before exercise was 10.70±1.11 pg/ml, whereas, after acute moderate exercise and acute strenuous exercise it was 12.00±1.09 pg/ml and 13.35±0.89 pg/ml respectively. Interestingly, after one month of moderate exercise the values decreased to; 8.80±0.65 pg/ml. Mean and SEM of TNF-α before exercise was 121.78±29.06 pg/ml. With acute moderate exercise and after acute strenuous exercise the values were 132.90±35.75 pg/ml and 112.05±29.89 pg/ml respectively. After one month moderate exercise the levels decreased to 94.95±27.29 pg/ml. The observed changes in both IL-6 and TNF-α levels before and after both moderate and strenuous exercise were statistically significant. Although there was a slight decrease in the value of both the cytokines after one month of regular moderate exercise compared to baseline value, the difference in the values was not statistically significant. However, both IL-6 and TNF-∝ levels showed overall statistically significant difference among the different grades of exercise. Plasma IL-6 and TNF-∝ increase with acute moderate exercise and IL-6 increases further with acute strenuous exercise. Their levels tend to fall below baseline with one month of regular moderate exercise indicating that regular moderate exercise has beneficial effects.

Naringin Inhibits Neuropathic Pain Produced by Lumbar 5 Spinal Nerve Ligation / 中山大学学报(医学科学版)

[Objective] To investigate the effect of naringin at different doses on the neuropathie pain produced by lumbar 5 spinal nerve ligafion (L5 SNL). [Methods] Using the method of behavioral test, we tested the 50% paw withdrawal threshold before and after intragastrieal application of naringin in the rats with L5 SNL. [Results] Naringin at 30, 90, 100 mg/kg but not at 10 mg/kg increased the 50% paw withdrawal threshold of 1.5 SNL rats significantly. Single application of Naringin (at 30 or 90 mg/kg) inhibited mechanical allodynia for around 6 hours, and the inhibitory effect persisted for 4 days after the cessation of the drug when naringin (30 mg/kg, daily) was consecutively applied for 7 days. [Conclusion] Intragastrical of naringin could relieve the neuropathic pain produced by peripheral nerve injury.

Clinical significance of detecting tumour necrosis factor-α, immtme globnlin and adenosine deaminase in cerebrospinal fluid of patients with intracranial infection / 中国医师进修杂志

Objective To investigate the diversify and clinical significance of tumour necrosis factor-alpha (TNF-α), immune globulin (Ig), adenosine deaminase (ADA) in cercbrospinal fluid (CSF) of patients with intracranial infection. Method The levels of TNF-α,Ig and ADA in CSF of 25 cases of purulent meningitis ,30 eases of cerebral tuberculosis ,28 cases of virus meningitis and 24 cases of controls were detected by ELISA, immunity velocity scattering nepbelometry and enzyme coupling method respectively. Results The levels of IgA, IgM, IgG, ADA, TNF-α were (41.72±11.31) mg/L(18.11± 2.62)mg/L, (181.60±41.19)mg/L, (13.41±3.42)U/L, (418.62±43.16)ng/L in cerebral tuberculosis patients. The levels of IgA, IgM, IgG, ADA and TNF-αwere (20.65±8.85)mg/L, (93.20±4.30)mg/L, (92.77±35.09)mg/L, (3.32±2.41) U/L, (476.93±45.16) ng/L in purulent meningitis patients, and those were (7.11±2.23)rag/L,(5.81±1.19)mg/L,(20.71±10. 54)mg/L,(2. 36±0. 44)U/L,(375.06±45.21) ng/L in virus meningitis patients. The levels of IgM,IgG and IgA in cerebral tuberculosis patients and purulent meningitis patients were significantly higher than those in virus meningitis patients and controls (P< 0.01). The levels of IgG,IgA heightened most markedly in cerebral tuberculosis patients. The activity of ADA in cerebra] tuberculosis patients was higher markedly than that in controls and the other patients(P< 0.01). The levels of TNF-α in purulent meningitis patients were higher than those in controls and virus meningitis patients(P< 0.05). The levels of TNF-α in purulent meningitis patients were the highest, and the next was in cerebral tuberculosis patients. But there was no significant difference of each index between viral meningitis patients and controls. Conclusions Detecting the activity of ADA in CSF is the most valuable in diagnosing cerebral tuberculosis. Synchronized detection of TNF-α,Ig, ADA may be have better clinical application in diagnosing intracranial infection.

Infliximab versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate:a randomized double blind phase Ⅲ trial in China / 中华风湿病学杂志

Objective To evaluate the efficacy and safety of infliximab plus methotrexate combination therpy in Chinese with rheumatoid arthritis patients.Methods This was a double-blind placebo-controlled phaseⅢclinical trial,173 patients who had active rheumatoid arthritis were randomised to placebo(n=86)or infliximab(n=87)group on a background of a stable dosage of methotrexate.Patients were assessed at weeks 0,2,6,14 and 18.Results At week 2,the American College of Rheumatology(20)response criteria,which represent a 20% improvement from baseline,the same results with swollen joint count,tender joint count,du- ration of morning stiffness,VAS score,CRP,ESR were achieved in 52.9% of patients,compared with 14.0% of patients receiving placebo plus methotrexate.A 20% improvement was achieved in 75.9% of infliximab plus methotrexate at week 18,compared with 48.8% of patients on placebo plus methotrexate(P=0.0003).A 50% improvement was achieved in 43.7% of infliximab plus methotrexate at week 18,compared with 25.6% of pa- tients on placebo plus methotrexate(P=0.011).Infliximab was well-tolerated;withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections were similar to those in the placebo group.There was only one case of tuberculosis in the treatment group.Conclusion Treatment with infliximab plus methotrexate is more effective than methotrexate alone in patients with active rheumatoid arthritis.It has rapid onset of effect and the efficacy is persistent.