Matrix metalloproteinases MMP-2 and MMP-9 as markers for the prediction of preeclampsia in the first trimester.

INTRODUCTION: Preeclampsia is a life-threatening condition for the mother and foetus. Globally, it is dia-gnosed in 10 mil. women every year, which accounts for 3% to 8% of all pregnancies. Currently there is no proven effective treatment for preeclampsia. The aforesaid text actualises the issue of predicting this complication. To determine the prognostic significance of matrix metalloproteinases-2 and -9 levels as early markers of preeclampsia, the present prospective study was conducted. MATERIALS AND METHODS: The levels of matrix metalloproteinases-2 and -9 were assessed in 72 patients. Thirty-four of them subsequently developed preeclampsia during pregnancy (20 patients with moderate preeclampsia, 14 patients with severe preeclampsia), and constituted the basic group; 38 patients made up the control group. RESULTS: In pregnant women with the subsequent development of preeclampsia, the level of matrix metalloproteinase-2 at 11-13 weeks of gestation was 155 ± 73.4 ng/mL and significantly exceeded its level in pregnant women without hypertensive disorders - 75.0 ± 32.8 ng/mL. The study conducted demonstrates a significantly lower concentration of matrix metalloproteinase-9 in pregnant women with preeclampsia compared to the control - 749 ± 296 ng/mL and 1,667 ± 552 ng/mL (P < 0.001). The performed research figures that in the first trimester, the cut-off value of matrix metalloproteinase-2 for predicting the development of preeclampsia is 102 ng/mL (sensitivity 88.24% and specificity 82.76%). For matrix metalloproteinase-9, a level of 980 ng/mL in the first trimester predicts the development of preeclampsia with a sensitivity of 85.29% and a specificity of 84.48%. CONCLUSION: The study established the cut-off values of matrix metalloproteinases-2 and -9 for predicting the development of preeclampsia in the first trimester.

Circulating matrix metaloproteinases as biomarkers in colorectalcancer.

The aim of this research is to offer comprehensive point of view related to perspective tumor markers called matrix metaloproteinases and their natural tissue inhibitors. Those markers are potentially useable mainly in postoperative follow-up in patients with colorectal cancer.

Effect of platelet rich plasma combined with core decompression on the repair of steroid-induced avascular necrosis of the femoral head and the MMP/TIMP in rabbits / 中国比较医学杂志

Objective To observe the effect of platelet rich plasma(PRP)combined with core decompression on the steroid-induced avascular necrosis of the femoral head(SANFH)and on MMP/TIM in rabbits.Methods A total of 42 New Zealand white rabbits were used in this study,and were randomly divided into 3 groups(decompression,combination and control groups,each n=14). The rabbit model of SANFH was established by i.m. injecting prednisolone acetate in the decompression group and combination group. The improved Landesberg method was used to make the platelet rich plasma. The decompression group received core decompression treatment while the combination group received PRP combined with core decompression for bone repair. X-ray photography of the hip joint of the two groups were taken at 2,6 and 10 weeks after the surgery,and the Lane-Sandhu X-ray scores and new bone area ratio were compared. Venous blood samples of the 3 groups were collected and the bilateral femoral heads were taken for further examination. The left femoral heads were used for histopathological observation and the right ones were used to determine the expression of the mRNA of MMP-2,MMP-9, TIMP-1, and TIMP-2. Results The levels of MMP-2 and MMP-9 in the decompression group were higher than that in the combination group and control group after surgery. The levels of TIMP-1 and TIMP-2 in the decompression group were significantly lower than the combination group and control group(P < 0.05). The IL-6 level and the rate of empty bone lacunae in the decompression group were significantly higher than the combination group and control group(P < 0.05), and that of the combination group was higher than the control group(P < 0.05). The combination group had a better joint imaging and histopathological evaluation than the decompression group after surgery. Conclusions Our findings demonstrate that PRP combined with core decompression can exert a positive effect on the MMP/TIMP and bone tissue repair in the treatment of steroid-induced avascular necrosis of the femoral head in rabbits.

Endothelin-1 promotes vascular smooth muscle cell migration across the artery wall: a mechanism contributing to vascular remodelling and intimal hyperplasia in giant-cell arteritis.

BACKGROUND: Giant-cell arteritis (GCA) is an inflammatory disease of large/medium-sized arteries, frequently involving the temporal arteries (TA). Inflammation-induced vascular remodelling leads to vaso-occlusive events. Circulating endothelin-1 (ET-1) is increased in patients with GCA with ischaemic complications suggesting a role for ET-1 in vascular occlusion beyond its vasoactive function. OBJECTIVE: To investigate whether ET-1 induces a migratory myofibroblastic phenotype in human TA-derived vascular smooth muscle cells (VSMC) leading to intimal hyperplasia and vascular occlusion in GCA. METHODS AND RESULTS: Immunofluorescence/confocal microscopy showed increased ET-1 expression in GCA lesions compared with control arteries. In inflamed arteries, ET-1 was predominantly expressed by infiltrating mononuclear cells whereas ET receptors, particularly ET-1 receptor B (ETBR), were expressed by both mononuclear cells and VSMC. ET-1 increased TA-derived VSMC migration in vitro and α-smooth muscle actin (αSMA) expression and migration from the media to the intima in cultured TA explants. ET-1 promoted VSMC motility by increasing activation of focal adhesion kinase (FAK), a crucial molecule in the turnover of focal adhesions during cell migration. FAK activation resulted in Y397 autophosphorylation creating binding sites for Src kinases and the p85 subunit of PI3kinases which, upon ET-1 exposure, colocalised with FAK at the focal adhesions of migrating VSMC. Accordingly, FAK or PI3K inhibition abrogated ET-1-induced migration in vitro. Consistently, ET-1 receptor A and ETBR antagonists reduced αSMA expression and delayed VSMC outgrowth from cultured GCA-involved artery explants. CONCLUSIONS: ET-1 is upregulated in GCA lesions and, by promoting VSMC migration towards the intimal layer, may contribute to intimal hyperplasia and vascular occlusion in GCA.

Association between matrix metaloproteinases 2-1306C/T polymorphism and the risk of coronary artery disease in Iranian population.

BACKGROUND: Coronary Artery Disease (CAD) represents the most important cause of sudden cardiac death. Interaction between genetic and environmental factors, individual susceptibility of the development of CAD is one of the MMP2 genes. Genetic variants' dysfunction of the MMP2 gene associated with the risk of CAD. The aim of the present study is to assess possible association between risk of Coronary Artery Disease and MMP2-1306C/T polymorphism. METHODS: This case-control study contains a total number of 344 subjects, including 215 patients with CAD and 129 of controls. Genomic DNA was isolated from whole blood and genotyping was performed by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR- RFLP) method. RESULTS: This study reveals the result that about 3.5% of CAD patients had TT genotype while 30.4% of them had CT genotype. Corresponding figures for subjects without CAD were zero and 52.6% respectively. These differences were statistically significant (P=0.002). Frequencies of T allele among patients with and without CAD were 18.71% and 26.28% respectively (p=0.04). The odds ratio between T allele and CAD was 0.64 (p=0.055). we couldn't trace significant differences among alleles in Gensini score, Gesnsini score's median among patients carried out TT, CT and CC genotypes were 4, 2 and 2 respectively (p=0.3). CONCLUSIONS: Result of this study provides some evidences that the MMP2-1306 polymorphism can be associated with coronary artery disease. Further longitudinal studies including more sample sizes are required to confirm this protective effect.

Role of inflammation in developmental odontogenic pathosis.

Periapical infection in the primary tooth may lead to periapical abscess, granuloma, radicular cyst and even osteomyelitis. The infection in primary teeth can also affect the developing successor teeth leading to hypomineralization, hypoplasia, arrest of tooth development, regional odontodysplasia, delayed eruption etc. The purpose of this article is to report a case of malformed permanent tooth in relation to overlying infected deciduous teeth. The probable role of inflammation in pathogenesis of the present condition is also being discussed.

Human umbilical cord-derived mesenchymal stem cell tansplantation for liver fibrosis and cirrhosis / 中国组织工程研究

BACKGROUND:Cirrhosis is a long-term consequence of chronic hepatic injury, which has no effective therapy. Mesenchymal stem cels have been shown to play a potential role in the treatment of liver fibrosis/cirrhosis. OBJECTIVE:To investigate the therapeutic effect and mechanism of human umbilical cord-derived mesenchymal stem cels on CCl4 induced liver fibrosis/cirrhosis in rats. METHODS:A CCl4-induced liver fibrotic/cirrhotic rat model was used, and human umbilical cord-derived mesenchymal stem cels were injectedvia the tail vein after modeling. Liver biochemical profile was measured by Beckman Coulter analyzer. Histopathological changes were assessed by Sirius red staining. The expressions of colagen type I, colagen type III, matrix metaloproteinases-2 and tissue inhibitor of matrix metaloproteinases-2 protein and mRNA in liver tissues were observed by immunohistochemistry, western blot and real-time PCR, respectively. RESULTS AND CONCLUSION:Liver biochemical profile indicated the transplantation of human umbilical cord-derived mesenchymal stem cels could improve the liver function of rats with liver fibrosis and cirrhosis. After cel transplantation, except 1-week cel transplantation group, the expressions of the matrix metaloproteinases-2 mRNA and protein were significantly increased, while the expressions of colagen type I, colagen type III and tissue inhibitor of matrix metaloproteinases-2 mRNA and protein significantly decreased, compared with the corresponding model groups. Human umbilical cord-derived mesenchymal stem cels play a role in the treatment of liver fibrosis and cirrhosis through upregulating the expression of matrix metaloproteinases-2 and lowering the expression of inhibitor of matrix metaloproteinases-2. With the continued presence of pathogenic factors, human umbilical cord-derived mesenchymal stem cel transplantation cannot reverse liver fibrosis or cirrhosis, and only delay the process of liver fibrosis or cirrhosis.

Expression of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase 1 in knee articular cartilage / 中国组织工程研究

BACKGROUND:Tissue inhibitor of matrix metaloproteinase 1 (TIMP-1) is the corresponding antagonist of matrix metaloproteinase 13 (MMP-13), and their balance between expression and functional activity exerts an important role in the metabolic state of the extracelular matrix. During the development of osteoarthritis, however, TIMP-1 and MMP-13 expressions and their expression ratio show unclear changes in DH guinea pigs. OBJECTIVE:To explore the expression levels of MMP-13 and TIMP-1 in DH guinea pigs with different ages, and to analyze the relationship between the ratio of MMP-13 to TIMP-1 and the age-dependent degenerative changes in the articular cartilage. METHODS:Twenty-four female Dunkin Hartley guinea pigs were sacrificed at age of 2, 4, 8, 12 months separately, with six animals at each time point. The knee joints were colected and gross visual appearance of the articular cartilage was observed, then were decalcified and prepared for paraffin sections. VG staining and Mankin score were used to analyze the histological changes. Immunohistochemistry was conducted to assess the expression levels of MMP-13 and TIMP-1 in the cartilage. Integrated absorbance values were used as the quantitive analysis calculated by Image pro-Plus 6.0. Linear regression analysis was done to analysis the relationship between Mankin score and the ratio of MMP-13/TIMP-1. RESULTS AND CONCLUSION:Normal appearance in the articular cartilage was observed in 2-month-old DH guinea pigs, while degenerative changes in the articular cartilage were shown in 4-month-old animals, which became severer with age. Significant difference was found in Mankin score between any two groups (P < 0.05). The ratio of MMP-13 to TIMP-1 increased with age, and the ratio was positively correlated to the Mankin score (P < 0.05). Age-related articular cartilage degeneration occurred in Dunkin Hartley guinea pigs at 4 months of age, and devoloped with age, which is related with the imbanlance of the expression ratio of MMP-13 to TIMP-1.

O uso da doxiciclina em dose subantimicrobiana em pacientes com doença periodontal: uma revisão de literatura / The use of subantimicrobial dose doxycycline in patients with periodontal disease: a review

A Periodontite Crônica é uma doença imunoinflamatória caracterizada pela perda óssea alveolar em indivíduos susceptíveis, tendo como fator etiológico principal o biofilme dental. O tratamento convencional desta doença é a terapia periodontal mecânica. Na tentativa de melhorar os parâmetros clínicos no controle da periodontite, a terapia de modulação do hospedeiro pode ser usada como auxiliar ao tratamento convencional, uma vez que diminui a resposta inflamatória do paciente, tendo em vista que as metaloproteinases da matriz têm um papel importante na regulação da destruição do tecido periodontal. Tal terapia pode ser realizada com doxiciclina em dose subantimicrobiana (DDS) de 20 mg administrada 2 vezes ao dia, para regular a atividade excessiva de colagenase no tecido gengival e fluido gengival crevicular. Dessa maneira, o presente estudo teve como objetivo avaliar o mecanismo de ação dessa droga, a eficácia do tratamento e a segurança no seu uso em longo prazo. Os dados obtidos a partir da revisão de literatura demonstram que a DDS como coadjuvante a raspagem e alisamento radicular (RAR) foi capaz de promover benefícios clínicos significativos, reduzir os níveis de colagenase, marcadores inflamatórios, reabsorção óssea e citocinas pró-inflamatórias, além de não alterar a microflora subgengival e não causar resistência a antibióticos. Os resultados sugerem ser eficaz e seguro o uso da DDS em longo prazo como coadjuvante na terapia periodontal quando usada por no mínimo 3 meses, com melhores resultados em 9 meses de uso. Futuros estudos longitudinais necessitam ser conduzidos a fim de definir a eficácia desse tratamento na história da doença periodontal.

The Chronic Periodontitis is an immuno-inflammatory disease characterized by alveolar bone loss in susceptible individuals, with the dental biofilm as main etiological factor. Conventional treatment of this disease is mechanical periodontal therapy. In an attempt to improve the clinical parameters in controlling periodontitis, host modulation therapy can be used as an adjunct to conventional treatment, since it reduces the inflammatory response of the patient, considering that matrix metalloproteinases have a role in regulation of periodontal tissue destruction. Such therapy can be accomplished with subantimicrobial dose doxycycline (SDD) 20 mg taken twice daily to regulate the excessive collagenase activity in gingival tissue and gingival crevicular fluid. Thus, the present study aimed to evaluate the mechanism of action of this drug, treatment efficacy and safety as long-term use treatment. The data obtained from the literature review shows that the SDD as an adjunct to scaling and root planing (SRP) was able to promote significant clinical benefits, reducing levels of collagenase, inflammatory markers, bone resorption and proinflammatory cytokines, and does not lead to change the subgingival microflora and antibiotic resistance. The results suggest that it is effective and safe the long-term use of SDD as an adjunct in periodontal therapy when used for at least 3 months, with better results at 9 months of use. Future longitudinal studies need to be conducted to establish the efficacy of this treatment in the history of periodontal disease.

Progress in study of matrix metalloproteinases and congestive heart failure / 中国药理学通报

The left ventricular (LV) myocardial remodeling process that occurs in various settings of congestive heart failure (CHF) had historically been attributed to intrinsic changes in the cardiac myocyte. However, it is now recognized that important changes also occur within the extracellular matrix (ECM) of the myocardium, contributing to the remodeling process. Matrix metalloproteinases are a family of proteolytic enzymes responsible for myocardial extracellular protein degradation.Several MMP species identified within the human myocardium may be dysregulated in congestive heart failure (CHF). The purpose of the present review is to present a brief overview of the matrix metalloproteinases (MMPs) within the myocardium that likely contributes to myocardial remodeling,to examine the results from basic studies to explore relationship with respect to MMPs activation and congestive heart failure.-