Activation of gelatinases in permanent human teeth after different experimental radiotherapy protocols

Abstract The objective of this study was to compare the activation of gelatinases in dentin-enamel junction (DEJ) and underlying dentin of permanent teeth after experimental radiotherapy in conventional and hypofractionated modalities. Newly extracted third molars (n = 15) were divided into three experimental radiotherapy groups: control, conventional (CR), and hypofractionated (HR) (n = 5 per group). After in vitro exposure to ionizing radiation, following standardized protocols for each modality, a gelatinous substrate was incubated on the tooth slices (n = 10 per group). Activation of gelatinases was measured by in situ zymography, expressed in arbitrary fluorescence units (mm2) from three tooth regions: cervical, cuspal, and pit. Fluorescence intensity was compared among radiotherapy protocols and tooth regions in each protocol, considering a significance level of 5%. Considering all tooth regions, the fluorescence intensity of the CR group was higher than the HR and control groups, both in DEJ and underlying dentin (p <0.001). In addition, the fluorescence intensity was higher in underlying dentin when compared to DEJ in all groups (p <0.001). Considering each tooth region, a statistically significant difference between CR and HR was only observed in the pit region of underlying dentin (p <0.001). Significant and positive correlations between fluorescence intensities in DEJ and underlying dentin were also observed (p <0.001). Experimental radiotherapy influenced the activation of gelatinases, as well as exposure to the conventional protocol can trigger a higher activation of gelatinases when compared to hypofractionated, both in DEJ and underlying dentin.

Resumo O objetivo deste estudo foi comparar a ativação de gelatinases na junção dentina-esmalte (DEJ) e na dentina subjacente de dentes permanentes após a radioterapia experimental nas modalidades convencional e hipofracionada. Os terceiros molares recém-extraídos (n = 15) foram divididos em três grupos de radioterapia experimental: controle, convencional (CR) e hipofracionada (HR) (n = 5 por grupo). Após a exposição in vitro à radiação ionizante, seguindo protocolos padronizados para cada modalidade, um substrato gelatinoso foi incubado nas fatias de dente (n = 10 por grupo). A ativação das gelatinases foi medida por zimografia in situ, expressa em unidades arbitrárias de fluorescência (mm2) de três regiões do dente: cervical, cúspide e fossa. A intensidade da fluorescência foi comparada entre os protocolos de radioterapia e as regiões do dente em cada protocolo, considerando um nível de significância de 5%. Considerando todas as regiões do dente, a intensidade de fluorescência do grupo CR foi maior do que a dos grupos HR e controle, tanto no DEJ quanto na dentina subjacente (p <0,001). Além disso, a intensidade da fluorescência foi maior na dentina subjacente quando comparada à DEJ em todos os grupos (p <0,001). Considerando cada região do dente, uma diferença estatisticamente significativa entre CR e HR foi observada apenas na região da fossa da dentina subjacente (p <0,001). Também foram observadas correlações significativas e positivas entre as intensidades de fluorescência no DEJ e na dentina subjacente (p <0,001). A radioterapia experimental influenciou a ativação das gelatinases, assim como a exposição ao protocolo convencional pode desencadear uma maior ativação das gelatinases quando comparada ao hipofracionamento, tanto no DEJ quanto na dentina subjacente.

Gelatinasas como marcadores de consumo crónico de alcohol: un estudio piloto en Uruguay / Gelatinases as markers of chronic alcohol consumption: a pilot study in Uruguay / Gelatinasas como marcadores de consumo crônico de álcool: um estúdio piloto em Uruguai

El consumo crónico de alcohol en Uruguay es un problema creciente, sin embargo, las determinaciones de biomarcadores consensuados no se realizan sistemáticamente ni se investigan otros marcadores potenciales. Para validar la hipótesis de que las metaloproteinasas de matriz con actividad gelatinasa son biomarcadores de consumo crónico de alcohol, se evaluaron muestras de sangre de 100 alcohólicos que comenzaron a atenderse en la Unidad de Trastornos Relacionados con el Alcohol y de 50 donantes sanos no alcohólicos. Las muestras de alcohólicos presentaron actividad de gelatinasas que triplicaron la de los controles y aumentos pequeños pero significativos en los niveles de γ-glutamil transferasa, aspartato-aminotransferasa y volumen corpuscular medio. Los valores de transferrina deficiente en carbohidratos fueron menores en alcohólicos que en controles. Estos resultados permiten proponer a las gelatinasas como los indicadores más sensibles del consumo sostenido de alcohol en la población analizada, ya que las enzimas hepáticas y el volumen corpuscular medio muestran una tendencia acorde con la literatura pero no alcanzaron valores asociados a la patología. Dado que la transferrina deficiente en carbohidratos es considerada el biomarcador indirecto más sensible y específico de consumo crónico de alcohol, los valores menores obtenidos en alcohólicos respecto de controles sugieren problemas metodológicos que podrían subsanarse aplicando otras técnicas de medida o por la presencia de interferencias que deben ser identificadas. Finalmente, estos hallazgos justifican una extensión de este trabajo piloto, así como estudios adicionales centrados en la participación de las metaloproteinasas de matriz con actividad gelatinasa en las cascadas de daño asociadas al consumo crónico de alcohol.

Chronic alcohol consumption in Uruguay is a growing problem, however, determinations of consensual biomarker are not performed systematically neither potential markers are explored. To validate the hypothesis that matrix metalloproteinases with gelatinase activity are biomarkers of chronic alcohol consumption, blood samples of 100 alcoholics that began medical treatment at the Unidad de Trastornos Relacionados con el Alcohol and 50 healthy non-alcoholic donors were evaluated. Alcoholic samples showed gelatinase activity that tripled that of controls and small but significant increases in levels of γ-glutamyl transferase, aspartate-aminotransferase and mean cellular volume. Carbohydrate deficient transferrin values were lower in alcoholics than in controls. These results allow proposing gelatinases as the most sensitive indicators of sustained alcohol consumption in the population analyzed since hepatic enzymes and mean cellular volume showed a tendency consistent with the literature but did not reach values associated with the pathology. Since carbohydrate-deficient transferrin is considered the most sensitive and specific indirect biomarker of chronic alcohol consumption, lower values in alcoholics related to controls suggest methodological problems that could be solved by applying other measurement techniques or by the presence of yet unknown interferences. Finally, these findings justify an extension of this pilot work, as well as additional studies focused on the participation of matrix metalloproteinases with gelatinase activity in the cascades of damage associated with chronic alcohol consumption.

O consumo crônico de álcool no Uruguai é um problema crescente, no entanto, as determinações consensuais de biomarcadores não são realizadas sistematicamente ou os potenciais marcadores são explorados. Para validar a hipótese de que as metaloproteinases de matriz com atividade gelatinase são biomarcadores do consumo crônico de álcool, foram avaliadas amostras de sangue cd 100 alcoólatras que começaram a ser tratadas na Unidad de Trastornos Relacionados con el Alcohol e 50 doadores não-alcoólatras saudáveis. As amostras alcoólicas apresentaram atividade de gelatinase que triplicou a dos controles e pequenos más significativos aumentos nos níveis de γ-glutamil transferase, aspartato-aminotransferase e volume médio celular. Os valores de transferrina deficientes em carboidratos foram menores nos alcoolistas que nos controles. Esses resultados permitem que as gelatinases sejam propostas como os indicadores mais sensíveis do consumo sustentado de álcool na população analisada, uma vez que as enzimas hepáticas e o volume celular médio apresentam uma tendência consistente com a literatura, mas não alcançaram valores associados à patologia. Como a transferrina deficiente em carboidratos é considerada o biomarcador indireto mais sensível e específico do consumo crônico de álcool, os valores mais baixos em alcoólatras do que em controles sugerem problemas metodológicos que poderiam ser sanados pela aplicação de outras técnicas de mensuração pela presença de interferências que deben ser identificadas. Finalmente, esses achados justificam uma extensão deste trabalho piloto, bem como estudos adicionais voltados para a participação de metaloproteinases de matriz com atividade de gelatinase nas cascatas de danos associados ao consumo crônico de álcool.

The effects of smoking on the expression of gelatinases in chronic periodontitis: a cross-sectional study

Abstract Smokers have a risk of developing periodontal disease. Matrix metalloproteinases (MMP) play a significant role in periodontal tissue destruction. In this study possible relationship between smoking and gingival tissue expression of gelatinases in chronic periodontitis patients relative to periodontally healthy subjects was investigated. Forty chronic periodontitis patients (20 smokers and 20 non-smokers) and forty periodontally healthy subjects (20 smokers and 20 non-smokers) were enrolled. The clinical periodontal measurements recorded, and gingival tissues harvested after that. After histologic evaluation, matrix metalloproteinases -2 and -9 expressions were analyzed immunohistochemically. In nonsmokers, higher expression of metalloproteinases -2 and -9 detected in chronic periodontitis group compared to the periodontally healthy group. In the smoker chronic periodontitis group, the expression of metalloproteinases-2 was lower than nonsmoker chronic periodontitis group. Statistically significant differences detected between smoker and nonsmoker periodontally healthy groups in metalloproteinases-2 expression. For metalloproteinases-9 expression, smoker chronic periodontitis group has lower values than nonsmoker chronic periodontitis group. In periodontally healthy group smokers showed higher metalloproteinases -9 expressions than non- smokers. Present findings support the role of gelatinases in chronic periodontitis pathogenesis. Based on the current results we conclude that smoking alters the expression of gelatinases in gingival tissues.

Clinical significance of neutrophil gelatinase-associated lipocalin in evaluating residual renal function after living donor kidney resection / 中华老年医学杂志

Objective To investigate the clinical significance of serum and urinary levels of neutrophil gelatinase-associated lipocalin (NGAL ) for evaluating changes of residual renal function after living donor kidney resection under different operation model in young versus elderly patients. Methods The clinical data of renal transplants were retrospectively analyzed by successfully using 66 living-related donors at the First Affiliated Hospital of Zhengzhou University from September 2016 to October 2017. According to the operation model and age ,renal donors were divided into 4 groups :group A (young/open) ,group B (young/laparoscopic) ,group C (aged/open) ,and group D (aged/laparoscopic).Blood and urinary NGAL and serum levels of creatinine ,cystatin C ,and other indices of renal function were assayed and collected before and at 1 ,3 ,7 days after operation. Results Both blood NGAL levels and urinary NGAL levels showed no statistically significant difference (all P>0.05) among four groups both before and after operation ,except that urinary NGAL was higher in group C (aged/open) than other groups ,at 1 day after operation ,(P = 0.03).The post-vs.pre-operation level dynamic changes of renal function were four or three times higher in urine or serum NGAL level than in serum creatinine or cystatin C level at 1 day after operation ,which showed an important role for predicting an early residual renal damage and relative treatment. Conclusions NGAL can be used as indices in evaluating changes of residual renal function after living donor kidney resection ,especially in the elderly receiving open kidney resection.

Expression and application of serum NGAL, KIM-1 and CysC in patients with renal tumor / 中国医师杂志

Objective To investigate the expression and clinical significance of serum neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and serum cystain C (CysC) in patients with renal tumor. Methods A total of 120 patients with renal tumor diagnosed in International Hospital of Zhejiang University from January 2016 and March 2016 was selected as the research object, and 60 patient medical volunteers were selected as control. The levels of NGAL and KIM-1 were determined by enzyme-linked immunosorbent assay ( ELISA) method, and the levels of serum CysC were determined by electrochemical luminescence method. The levels of NGAL, KIM-1, and CysC were compared, and their relevance was analyzed. Results The levels of NGAL, KIM-1, and CysC in research object were signifi-cantly higher than the control group; the levels of NGAL, KIM-1, and CysC in malignant tumor patients were significantly higher than the benign tumor;the levels of NGAL, KIM-1, and CysC in one level of ser-um tumor were lower than the two levels, three levels, and four levels of tumor patients. With the more Furhman grading, the levels of NGAL, KIM-1, and CysC were higher, the differences were statistically sig-nificant (P<0. 05). The levels of serum NGAL, KIM-1, and CysC were significantly related to renal dam-age degree. The levels of serum NGAL were significantly positively related to KIM-1 and CysC ( r= 0. 812 and 0. 765 ) . The levels of serum KIM-1 expression were significantly positively related to CysC ( r =0. 832) (P<0. 05). Multiple regression analysis showed that the levels of serum NGAL, KIM-1, and CysC were significantly related to patients with renal tumor Furhman classification ( P<0. 05 ) . Conclusions The levels of NGAL, KIM-1 and CysC were significantly increased in patients with renal tumor renal tumor, the higher the clinical stage, the higher expressive level, and were significantly related to renal damage de-gree. NGAL, KIM-1, and CysC can be used as the diagnostic markers of renal tumor.

Predictive value of NGAL and renal injury molecule 1 in 28-day mortality of neonatal sepsis with re-nal injury / 中国医师杂志

Objective To investigate the prognostic value of serum neutrophil gelatinase-associated lipid transport protein (NGAL) and renal injury molecule 1 (KIM-1) in assessing neonatal sepsis with a-cute renal injury. Methods A total of 63 cases of renal injury with neonatal sepsis was collected from De-partment of Pediatrics, Affiliated Children's Hospital of Capital Institute of Pediatrics. The general condition of the patients, and neonatal critical case score ( NCIS) were recorded. The expressions of NGAL and KIM-1 in serum of all children were measured by venous blood and urine. Each case was followed up for 28 days to track the death of newborns. Pearson correlation analysis was used to test the correlation among NGAL, KIM-1, and NCIS;Multivariate regression analysis was used for NGAL, KIM-1, and other risk factors asso-ciated with neonatal sepsis kidney injury 28 days mortality. Receiver operating characteristic ( ROC) curve was used to compare the value of NGAL and KIM-1 in the prognosis of neonatal sepsis renal injury. The val-ues of NGAL and KIM-1 in the prognosis of neonatal sepsis renal injury were analyzed by ROC curve. Re-sults ⑴ After 28 days of follow-up, 63 cases of neonatal sepsis, and 22 died were found, which was ac-counted for 34. 92 percent of the total. ⑵ Compared to the survival group, the expressions of NGAL and KIM-1 in the death group were increased ( P<0. 01 ) . ⑶ Pearson correlation analysis showed that NGAL and KIM-1 expressions in peripheral blood were negatively correlated with NCIS. ⑷Multivariate regression analysis showed that NGAL and KIM-1 were independent risk factors for neonatal sepsis kidney injury ( P<0. 01). ⑸ ROC curve analysis showed that the area under the curve of NGAL and KIM-1 was 0. 79 (95％CI:0. 75-0. 93), and 0. 84 (95％ CI:0. 71-0. 90), NGAL and KIM-1 were better than single detection with NGAL, or KIM-1, area under curve (AUC) was 0. 89 (95％ CI:0. 78-0. 94) (P<0. 01). Sensitiv-ity of KIM-1 was superior to that of NGAL, and specificity of NGAL was superior to KIM-1. The sensitivity and specificity of both were better than single detection with NGAL and KIM-1. Conclusions NGAL and KIM-1 have good predictive value in assessing neonatal sepsis kidney injury mortality.

Changes of plasma NGAL and serum CysC in patients with essential hypertension and its clinical significance / 中国基层医药

Objective To explore the levels of neutrophil gelatinase -associated lipocalin(NGAL)and Ser-um cystatin C(CysC)in plasma in essential hypertension(EH)and to discuss their clinical significance.Methods 92 patients with essential hypertension were selected as EH group.At the same time,88 healthy subjects were selected as the healthy control group.The levels of plasma NGAL,serum CysC and some other biochemical markers were detected.The results were statistically processed.Results The level of Plasma NGAL in EH group was(149.22 ± 11.52)μg/L and the level of serum CysC in EH group was(0.92 ±0.03)mmol/L.The level of Plasma NGAL in the healthy control group was(101.4 ±7.71)μg/L and the level of serum CysC in the healthy control group was(0.71 ± 0.02)mmol/L.The levels of Plasma NGAL and serum CysC were significantly increased in EH group compared with those of the healthy control group(F =27.491,P <0.01;F =24.646,P <0.01).Plasma NGAL was positively corre-lated with the degree of EH and the level of serum CysC(r =0.48,P <0.01).Conclusion Plasma NGAL and serum CysC were significantly increased in EH patients,with a significant positive correlation to the degree of nephropathy damage.Both of them can become diagnostic measurements for early diagnosis of nephropathy damage induced by EH.

Value of neutrophils gelatinases related lipid a carrier protein and renal injury molecule-1 for early diagnosis in adult cardiac surgery after acute renal injury / 中国医师进修杂志

Objective To explore the value of neutrophils gelatinases related lipid a carrier protein (NGAL),renal injury molecule-1 (KIM-1) and serum creatinine (SCr) for early diagnosis in adult cardiac surgery after acute renal injury (AKI).Methods Blood and urine samples of 65 cardiac surgery patients before and 24,48,72 h after surgery were collected,SCr,urine NGAL and KIM-1 levels was detected,among whom AKI occurred in 34 cases(AKI group),did not occur in 31 cases (non AKI group),and they were compared with 20 cases of healthy physical examination (control group).Logistic regression model was used to judge the value of early diagnosis of SCr,urine NGAL and KIM-1.Results The incidence of AKI after cardiac surgery was 52.31％ (34/65).The SCr,urine NGAL and KIM-1 levels in AKI group and non AKI group before and 24,48,72 h after surgery were significantly higher than those in control group [SCr:(62.44 ±22.26),(77.38 ±24.38),(98.24 ±25.02),(98.14 ±45.26)μmol/L and (56.67 ±21.68),(59.25 ± 15.58),(55.40 ±22.91),(40.10 ±23.45)μmol/L vs.(16.43 ±5.01)μmol/L;urine NGAL:(4.81 ±0.65),(9.48 ±3.29),(11.87 ±3.93),(7.66 ± 1.52) μg/L and (4.67 ±0.53),(8.89 ± 2.64),(11.46 ± 3.60),(7.47 ± 1.63)μg/L vs.(2.87 ± 0.48) μg/L; KIM-1:(47.93 ± 5.54),(61.89 ± 12.44),(100.21 ± 27.32),(67.69 ± 8.72) μ g/L and (47.12 ± 4.08),(56.38 ± 9.27),(90.14 ± 27.26),(69.40 ±8.90) μ g/L vs.(32.21 ± 12.54)μ g/L] (P ＜ 0.01).Urine NGAL and KIM-1 levels in AKI group and non AKI group 24,48,72 h after surgery were significantly higher than those before surgery (P＜ 0.01).SCr,urine NGAL and KIM-1 levels in AKI group 24 h after surgery were significantly higher than those in non AKI group (P＜ 0.01).Twenty-four hours after surgery,the sensitivity and specificity of urine NGAL,KIM-1 in the diagnosis of AKI,compared with that of SCr had no statistical significance (P ＞ 0.05).Conclusions The adults who accept extracorporeal circulation cardiac surgery appear high incidence of AKI.Twenty-four hours after surgery,early biological markers-urine AKI,KIM-1,has similar sensitivity and specificity with traditional diagnostic gold standard of SCr.

Matrix metalloproteinases 2 and 9 expression in canine normal prostate and with proliferative disorders / Expressão de metaloproteinases de matriz 2 e 9 na próstata canina normal e com lesões proliferativas

In this study the expression of metalloproteinases 2 (MMP-2) and 9 (MMP-9) in canine normal prostates and with proliferative disorders was evaluated to verify the role of these enzymes in extracellular matrix remodeling (ECM) and in the tissue invasion process. A total of 355 prostatic samples were obtained, from which 36 (10.1%) were normal prostates, 46 (13.0%) with benign prostatic hyperplasia (BPH), 128 (36.1%) with proliferative inflammatory atrophy (PIA), 74 (20.8%) with prostatic intraepithelial neoplasia (PIN), and 71 (20.0%) with prostatic carcinoma (PC). Difference in cytoplasmic immunohistochemical staining of MMP-2 and MMP-9 between acinar epithelium and periacinar stroma was found regarding the different diagnosis. The correlation between MMP-2 and MMP-9 expression in relation to the number of labeled cells in acinar epithelium and periacinar stroma, as well as to the staining intensity in the periacinar stromal cells was evidenced in canine prostates with PIA. In conclusion, MMP-2 and MMP-9 expression has a variation in canine prostate according to the lesion, with lower expression in normal tissue and with BPH, and higher expression in those with PIA, PIN and PC. Moreover, the inflammatory microenvironment of the PIA has influence in the activity of both enzymes.

Este estudo teve como objetivo avaliar a expressão das metaloproteinases 2 (MMP-2) e 9 (MMP-9) em próstatas caninas normais e com desordens proliferativas, verificando o papel dessas enzimas na remodelação da matriz extracelular (MEC) e no processo de invasão tecidual. Um total de 355 amostras prostáticas foram obtidas, sendo 36 (10,1%) normais, 46 (13,0%) com hiperplasia prostática benigna (HPB), 128 (36,1%) com atrofia inflamatória proliferativa (PIA), 74 (20,8%) com neoplasia intraepitelial prostática (PIN) e 71 (20,0%) com carcinoma prostático (CP). Houve diferença de imunomarcação citoplasmática para MMP-2 e MMP-9 entre o epitélio acinar e o estroma periacinar, quanto aos diferentes diagnósticos. Observou-se correlação entre a expressão de MMP-2 e MMP-9 em relação ao número de células marcadas no epitélio acinar e estroma periacinar, bem como para a intensidade de marcação das células estromais periacinares em próstatas caninas com PIA. Conclui-se que há variação na expressão de MMP-2 e MMP-9 em próstatas caninas de acordo com a lesão, com menor expressão em próstatas caninas normais e com HPB, e maior naquelas com PIA, PIN e CP. Ainda, o microambiente inflamatório na PIA influencia a atividade de ambas as enzimas.

Value of urine L-FABP and its combination with urine NGAL in early diagnosis of acute kidney injury after cardiac surgery in adults / 中华肾脏病杂志

Objective To investigate the value of urinary liver-type fatty acid-binding protein (L-FABP),neutrophil gelatinase-associated lipocalin (NGAL) and their combination in predicting the development and the severity of acute kidney injury (AKI) following cardiac surgery in adults. Methods Scr,urinary L-FABP and NGAL corrected by urine creatinine at preoperation,0 h and 2 h postoperative time points were examined.The differences of above indexes between AKI and non-AKI groups were compared.Receiver operating characteristic (ROC)curves and area under curves (AUC) were used to evaluate the diagnostic value of urinary L-FABP,NGAL and their combination for AKI. Results The cohort consisted of 109 patients,26(23.9％) developed AKI,and AKIN stage Ⅰ, Ⅱ and Ⅲ was 46.2％,34.6％ and 19.2％ respectively.Levels of urinary L-FABP and NGAL were significantly higher in AKI patients at 0 h and 2 h postoperatively.AUC to predict AKI or AKI stage Ⅱ-Ⅲ was 0.81 to 0.87 using either of the biomarkers.The performance of combining two biomarkers was better with AUC of 0.911 to 0.927. Conclusions Urinary L-FABP and NGAL increase at the early stage after cardiac surgery.Combination of these two biomarkers enhances the accuracy of the early diagnosis of postoperative AKI after cardiac surgery before a rise of Scr.

Mechanical ventilation and volutrauma: study in vivo of a healthy pig model

Mechanical ventilation is essential in intensive care units. However, it may itself induce lung injury. Current studies are based on rodents, using exceptionally large tidal volumes for very short periods, often after a "priming" pulmonary insult. Our study deepens a clinically relevant large animal model, closely resembling human physiology and the ventilator setting used in clinic settings. Our aim was to evaluate the pathophysiological mechanisms involved in alveolo/capillary barrier damage due to mechanical stress in healthy subjects. We randomly divided 18 pigs (sedated with medetomidine/tiletamine-zolazepam and anesthetised with thiopental sodium) into three groups (n=6): two were mechanically ventilated (tidal volume of 8 or 20 ml/kg), the third breathed spontaneously for 4 hours, then animals were sacrificed (thiopental overdose). We analyzed every 30' hemogasanalysis and the main circulatory and respiratory parameters. Matrix gelatinase expression was evaluated on bronchoalveolar lavage fluid after surgery and before euthanasia. On autoptic samples we performed zymographic analysis of lung, kidney and liver tissues and histological examination of lung. Results evidenced that high Vt evoked profound alterations of lung mechanics and structure, although low Vt strategy was not devoid of side effects, too. Unexpectedly, also animals that were spontaneously breathing showed a worsening of the respiratory functions.

Effect of curcumin on serum levels of gelatinases in patients with unstable angina pectoris / 心血管康复医学杂志

Objective: To investigate effect of curcumin on serum gelatinases levels in patients with unstable angina pectoris（UAP）. Methods： A total of 80 UAP patients admitted from January 2010 to September 2010 were enrolled and randomly divided into curcumin treatment group (n=40) and routine treatment control group (n=40). Serum levels of gelatinases [contain matrix metalloproteinase（MMP）-2 and -9) of the two groups were measured before and 30d after treatment. Results：Compared with before treatment , after treatment, serum gelatinases levels significantly decreased [MMP-2：（52.64±6.77）ng/ml vs. （32.65±1.67）ng/ml，MMP-9：（56.75±7.34）ng/ml vs.（35±1.88）ng/ml ] (P<0.01) in curcumin treatment group (P<0.01), and they were significantly lower than those of routine treatment control group [MMP-2：（32.65±1.67）ng/ml vs.（37.78±2.76）ng/ml，MMP-9：（35±1.88）ng/ml vs.（40.23±1.95）ng/ml ] , P<0.05 all. Conclusion：Curcumin could decrease serum levels of gelatinases in patients with unstable angina pectoris, and possesses effect of stabilization coronary artery plaque.

Effect of curcumin on serum gelatinases level in patients with unstable angina pectoris / 心血管康复医学杂志

Objective:To investigate effect of curcumin on serum gelatinases level in patients with unstable angina pectoris (UAP). Methods:A total of 80 UAP patients admitted from January 2010 to September 2010 were enrolled and randomly divided into curcumin treatment group (n=40) and routine treatment control group (n=40). Serum levels of gelatinases [contain matrix metalloproteinase (MMP)-2 and -9] of the two groups were measured before and 30d after treatment.Results: Compared with before treatment , after treatment, serum levels of gelatinases significantly decreased [MMP-2:(52.64±6.77)ng/ml vs.(32.65±1.67)ng/ml,MMP-9:(56.75±7.34)ng/ml vs.(35±1.88)ng/ml]in curcumin treatment group (P<0.01), and they were significantly lower than those of routine treatment control group[MMP-2:(32.65±1.67)ng/ml vs.(37.78±2.76)ng/ml,MMP9:(35±1.88)ng/ml vs.(40.23±1.95)ng/ml]],P<0.05. Conclusion:Curcumin could decrease serum levels of gelatinases in patients with unstable angina pectoris, and possesses effect stabilizing coronary artery plaque.

Análise do padrão de expressão de MMP-2, -9 e -8 em tecido humano pulpar normal e inflamado / Analysis of the expression perfile of MMP-2, -9 and -8 in normal and inflamed human pulp tissue

As metaloproteinases da matriz (MMPs) foram relacionadas a diversas doenças inflamatórias como artrite e também ao câncer. O presente trabalho tem por objetivo estabelecer o papel da MMP-2, MMP-9 e MMP-8 no processo de inflamação pulpar. Foram adotadas as seguintes hipóteses nulas: (1) o padrão de expressão das MMP-2, MMP-9 e MMP-8 não sofre alteração nos diferentes estágios da polpa humana: normal, reversível, transição, irreversível ou necrose; (2) não há diferença de expressão das MMP-2, -9 e MMP-8, considerando-se um mesmo estágio de inflamação tecidual pulpar. Os métodos utilizados foram: (I) Obtenção dos espécimes, que foram divididos em grupos de acordo com critérios adotados de semiologia subjetiva e objetiva. Obtiveram-se os seguintes grupos: GI (Controle) dentes hígidos (n=7); GII (Pulpite Reversível n=4); GIII (Pulpite Transição n=4); GIV (Pulpite Irreversível/Necrose n=8). Logo após exodontia, os dentes obtidos foram cortados ligeiramente abaixo da junção amelodentinária e fixados em formol a 10% por 48h. Foram lavados em água corrente (24h) para então serem processados histologicamente. Foram obtidas secções de 4m, aderidas em lâminas silanizadas e submetidas à imunomarcação (Técnica da Peroxidase), utilizando os anticorpos anti MMP-2, MMP-9 e MMP-8 humanos. A presença de imunomarcação foi realizada através da análise semi-quantitativa por escores, sendo que a quantificação de marcação por corte seguiu o seguinte escore: 0= ausente; 1= leve; 2= moderada; 3= intensa. Realizou-se teste estatístico não paramétrico Kruskal-Wallis, p<0,05. As comparações intergrupos revelaram, para CO: (1)MMP-2 - GI=GII=GIII, GIII=GIV, GI>GIV (p<0,01) e GII>GIV (p<0,05); (2)MMP-9 GI=GII=GIV, GII=GIII e GIII>GI (p<0,01); (3)MMP-8 GI=GII=GIII=GIV. Na região central da polpa, obteve-se: (1)MMP-2 GI=GII=GIII, GIII=GIV, GI>GIV (p<0,001) e GII>GIV (p<0,01); (2)MMP-9 GI=GII=GIII, GIII=GIV, GIV>GI (p<0,001) e GIV>GII (p<0,01); (3)MMP-8 GI=GII, GIII=GIV, GIII>GI (p<0,05),...

The matrix metalloproteinases (MMPs) have been related to various inflammatory diseases, such as arthritis, as well as to cancer. The aim of the present study was to establish the role of MMP-2, MMP-9 and MMP-8 in the process of dental pulp inflammation. The following null hypotheses were adopted: (1) the pattern of MMP-2, MMP-9 and MMP-8 expression does not undergo alteration in the following different stages of human pulp: normal, reversible, transition, irreversible or necrosis; (2) there is no difference in the expression of MMP-2, -9 and MMP-8, when considering the same stage of pulp tissue inflammation. The methods used were: (I) Obtainment of specimens, which were divided into groups according to the subjective and objective criteria of semiology adopted. The following groups were obtained: GI (Control) healthy teeth (n=7); GII (Reversible Pulpitis n=4); GIII (Transition Pulpitis n=4); GIV (Irreversible Pulpitis/Necrosis n=8). Soon after extraction the teeth obtained were cut slightly below the amelodentinal junction and fixed in 10% formol for 48h. They were washed under running water (24h) and were histologically processed afterwards. Sections of 4m were obtained, adhered to silanized slides, and submitted to immunomarking (Peroxidase Technique), using human anti MMP-2, MMP-9 and MMP- 8 antibodies. The presence of immunomarking was determined through semi-quantitative analysis by scores, and marking by cut was quantified using the following score: 0= absent; 1= slight; 2= moderate; 3= intense. The Kruskal-Wallis non-parametric statistical test was performed, p<0.05. Intergroup comparisons revealed the following: for CO: (1)MMP-2 - GI=GII=GIII, GIII=GIV, GI>GIV (p<0.01) and GII>GIV (p<0.05); (2)MMP-9 GI=GII=GIV, GII=GIII and GIII>GI (p<0,01); (3)MMP-8 GI=GII=GIII=GIV. In the central region of the pulp, the following results were obtained: (1)MMP-2 GI=GII=GIII, GIII=GIV, GI>GIV (p<0.001) and GII>GIV (p<0.01); (2)MMP-9 GI=GII=GIII, GIII=GIV, GIV>GI...

Effect of photochemotherapy on expression of gelatases / 上海第二医科大学学报

Objective To determine the effect of photochemotherapy on the expression of gelatinases. Methods Reverse transcription-polymerase chain reaction and gelatine zymography were employed to detect the effect of photochemotherapy on the expression and bioactivity of gelatinases at mRNA and protein levels respectively. Results Combination of ultraviolet A(UVA,0.8-2.0 J/cm2) and 8-methoxypsoralen(8-MOP,100 ng/mL) resulted in a decrease in the expression and bioactivity of gelatinases. Conclusion Photochemotherapy can inhibit the angiogenesis of endothelial cells through downregulating the expression and bioactivity of gelatinases.

Changes of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sputum from Moderate to Severe Acute Asthma after Corticosteroid Therapy / 소아알레르기및호흡기학회지

PURPOSE: Bronchial asthma is an inflammatory respiratory disease characterized by the activation of inflammatory cells and its infiltration. It has been recently reported that MMP- 9 dose an importance role in the movement of inflammatory cells through basal membrane, that the function may be suppressed by TIMP-1. We studied to know the change of MMP-9 and TIMP-1 in sputum before and after corticosteroid (CS) therapy, and the relation with MMP-9/TIMP-1 ratio and improvement of FEV1. METHODS: Seventeen acute moderate to severe asthmatics were selected as was a control group of 17 healthy children. MMP-9 and TIMP-1 in sputum were measured on the 0 day, 7 days and 3 months later and observed as to the flow of time. FEV1 was measured before the CS therapy and 3 months later, and the change of FEV1 & FEV1 at 3 months were compared with the relation of MMP-9/TIMP-1 ratio. RESULTS: Sputum MMP-9 was lowered more at 7 days and 3 months compared with 0 day (P< 0.05). Sputum TIMP-1 was significantly high on 7 days (P< 0.05) and then had a tendency to decrease until 3 months (P< 0.05). MMP-9/TIMP-1 ratio decreased according to the flow of time (P< 0.05). MMP-9/TIMP-1 ratio at 3 months closely correlated with the change of FEV1 (r=0.65, P< 0.05). CONCLUSION: These data suggest that the overproduction of MMP-9 after asthma exacerbation correlates with airway inflammation and TIMP-1 production might contribute to airway fibrosis. MMP-9/TIMP-1 ratio at 3 months correlates with improvement of pulmonary function after CS therapy.

Effects of Sinomenine on the expression of cytoskeleton and MMP-2, MMP-9 in renal tubular epithelial cells / 中华肾脏病杂志

Objective To explore the effects of Sinomenine (Sin) on phenotype transdifferentiation in renal tubular epithelial cells. Methods Mice primary tubular epithelial cells and cell line (MCT) were cultured in vitro. Model group cells were stimulated by IL-1?(10 ng/ml). The cells of Sin group were co-incubated with Sin(10, 100 ,500?mol/L) simultaneously. The cells without IL-1?and Sin treatment were regarded as control group. The protein expression of?-smooth muscle actin (SMA) and Vimentin was assessed by immunohistochemistry and Western blotting. The mRNA expression of?-SMA and Vimentin was examined by RT-PCR. Secretion of matrix metalloproteinases was determined by zymography. Results The mRNA expression and protein level of?-SMA and Vimentin, and the enzyme activity of MMP-2 and MMP-9 in tubular epithelial cells stimulated with IL-1?were significantly higher than those in the controls. Sinomenine significantly reduced the expression levels of protein and mRNA of?-SMA and Vimentin. At the same time, the MMP-2 and MMP-9 activities were reduced markedly. Conclusion Sinomenine can decrease the transdifferentiation in renal tubular epithelial cells stimulated by inflammatory factor IL-1?and prevent renal interstitial fibrosis.

Expressions of gelatinases in diffuse proliferative lupus nephritis and its clinical significance / 中华风湿病学杂志

Objective To investigate the roles and significances of MMP-2 and MMP-9 in diffuse proliferative lupus nephritis by repeated renal biopsy.Methods Seventeen patients diagnosed by renal biopsy as WHO typeⅣlupus nephritis were analyzed by immunohistochemistry staining for MMP-2 and MMP-9. Double staining for MMP-2 and MT1-MMP,MMP-9 and CD68 were also performed.Patients had repeated renal biopsy after followed up for 2.5 years.The relationship between expressions of gelatinases and pathological activity index and clinical data were studied.Results MMP-2 immunoreactivity was detected in normal controls and was increased in diffuse proliferative lupus nephritis.MMP-9 staining,which was almost negative in normal giomeruli,was increased much more significantly in diffuse proliferative lupus nephritis. The immunoreactivity of MMP-2 and MMP-9 was positive in MT1-MMP staining and CD68-positive macrophages, respectively.The expression of MMP-2 and MMP-9 was reduced by 70% and 62% in 10 patients whose clinical condition was partially alleviated,while the expressions in 7 patients whose clinical condition was not alleviated,were only reduced by 27% and 32%.The staining for MMP-2 and MMP-9 were correlated with activity index of lupus nephritis and proteinuria.Conclusion Up-regulation of gelatinases expression in diffuse proliferate lupus nephritis is correlated to activity index of the disease.

Study of correlation between expression of matrix matalloproteinase-9 and cerebral edema after diffuse brain injury in rats / 中华创伤杂志

Objective To observe the expressions of matrix metalloproteinase-9 mRNA and the change of cerebral edema after diffuse brain injury in rats and discuss their correlation.Methods Marmaruu's diffuse brain injury model of rat was made.Real-time quantitative RT-PCR,dry-wet meth- od,histological techniques and electron microscope were used to determine the expressions of MMP-9 containing water in brain tissue and inflammatory reaction and uhrastructural changes of blood capillary at different time phases after truama.Results The expressions of MMP-9 mRNA started to increase at 1 hour,peaked at 12 hours(P

Role of gelatinase and interleukin-8 in the pathogenesis of premature rupture of membrane / 中华围产医学杂志

Objective To study the role of Gelatinase and interleukin 8 (IL 8) in premature rupture of membrane (PROM). Methods Sixty pregnant women were divided into two groups. In the observation group, were the pregnant women ( n=30 ) complicated with PROM. The women whose membranes ruptured either normally or manually in cesarean delivery were in the control group. Activities of total gelatinases in amniotic fluid were calculated after the experiment of enzyme linked immunosorbent assay (ELISA) with actin labeled gelatin. The electrophoresis of gelatinase was taken according to reference. IL 8 was determined by sandwich ELISA. Results (1) The activity of total gelatinases of amniotic fluid in observation and control groups during the period before labor, latent stage and active stage were (85?10)?g/L?12 h, (91?7)?g/L?12 h, (104?23)?g/L?12 h, (49?15)?g/L?12 h, (58?15)?g/L?12 h and (102?29)?g/L?12 h respectively,the activity of total gelatinases in active stage was significantly higher than that before labor ( P