Assessment of aprotinin influence on periodontal clinical status and matrix metalloproteinases 1, 2 and their tissue inhibitors saliva concentrations in patients with chronic periodontitis

Pietruska, Małgorzata; Pietruski, J; Skurska, Anna; Bernaczyk, A; Zak, Janusz; Żelazowska, Beata; Dolińska, Ewa; Paniczko-Drezek, A; Wysocka, Jolanta

doi:10.2478/v10039-009-0027-2

Cited by 16 publications

(15 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…44 WenhuaXi Road, Ji'nan, 250012, Shandong Province, P.R. China; Tel: 86-531-88382011; Fax: 86-531-88382264; E-mail: tjulx2004@sdu.edu.cn components, which are believed to contribute to a wide array of pathological conditions related to tumor metastasis, angiogenesis, cardiovascular disease, osteoarthritis, rheumatoid arthritis, chronic periodontitis, pulmonary emphysema, skin ulceration, atherosclerosis, central nervous system disease, type I diabetes, myocarditis and dilated cardiomyopathy, coronary artery disease, multiple sclerosis, congestive heart failure, and so forth [5][6][7][8][9][10][11]. Accordingly, effective controlling MMP activity(s) using natural or synthetic smallmolecule inhibitors (MMPIs) represents an attractive and potential area of drug development to intervene in the MMPrelated disorders [12,13].…”

Section: Mmp and Mmpimentioning

confidence: 99%

Recent Advances in the Development of MMPIs and APNIs Based on the Pyrrolidine Platforms

2010

MRMC

View full text Add to dashboard Cite

Pyrrolidine scaffold has been widely used to design a variety of N-heterocyclic derivatives towards various targets. Amongst them, matrix metalloproteins (MMPs) and aminopeptidase N (APN) represent two kinds of important metalloproteinase targets which have been proved to be tightly related to tumor proliferation, invasion, metastasis and angiogenesis. As a result, their respective inhibitors, namely MMP inhibitors (MMPIs) and APN inhibitors (APNIs), have been systematically studied in our group for many years. Recent advances in the elucidation of MMPIs and APNIs based on the pyrrolidine platforms are briefly reviewed in this paper.

show abstract

Section: Mmp and Mmpimentioning

confidence: 99%

Recent Advances in the Development of MMPIs and APNIs Based on the Pyrrolidine Platforms

2010

MRMC

View full text Add to dashboard Cite

show abstract

“…That is, over-expression or high activation of MMPs has been causally linked with the pathological destruction of connective tissue and the ensuing pathological disorders characterized by the breakdown of ECM components or connective tissues [1]. These diseases include cancer, osteoarthritis (OA), rheumatoid arthritis (RA), angiogenesis, chronic periodontitis, pulmonary emphysema, skin ulceration, atherosclerosis, gingivitis, central nervous system disease, type I diabetes, myocarditis and dilated cardiomyopathy, coronary artery disease, multiple sclerosis (MS), congestive heart failure, cardiovascular disease and so on [8][9][10][11][12][13]. On the basis of their primary roles in various oncologic events, the MMPs have been a highly active set of targets for the design of therapeutic agents to intervene the MMPrelated pathological states, such as carcinogenesis and arthritis [14].…”

Section: Introductionmentioning

confidence: 99%

An Updated Patent Therapeutic Agents Targeting MMPs

Shi¹,

Shi³

et al. 2012

PRA

View full text Add to dashboard Cite

The traditional consensus that matrix metalloproteinases (MMPs) has correlation with various pathological and physiological processes led to the exploitation of a vast number of natural or synthetic broad-spectrum MMP inhibitors (MMPIs) for the prophylaxis or treatment of various MMP-related disorders, such as autoimmune, inflammatory, cardiovascular, neurodegenerative, respiratory diseases, and malignant cancer as well. Yet the unsatisfactory preclinical and/or clinical results motivated further investigation of the physiological roles of certain MMP subtypes. Despite the intricate and complicated MMP functions in normal physiology and disease pathology, the effort of designing specific inhibitors that can selectively target certain MMP family members for individualized therapy is ongoing and remains an arduous task. Success will rely on continued insight into the biological roles of these multifaced proteases. In our previous effort, we summarized various MMPIs that have entered preclinical or clinical trials as well as the patents in regard to MMPIs (Recent Pat Anticancer Drug Discov. 2010; 5(2): 109-41). In our on-going review, to illustrate the major challenges in MMP validation as druggable targets, we highlighted the physiological and pathological roles of representative MMPs, with an emphasis on description of the newly emerging MMPI-based patents, in particular, the inhibitors containing sulfonamide or sulfone motif. By analyzing the structural characteristics and selectivity profiles of these supplementary inhibitors, we hereby described their pharmaceutical application, and also expanded the strategies for potent MMPI design.

show abstract

“…Pacientes com DP após o tratamento periodontal não cirúrgico possuíam níveis mais altos de MMP-1, MMP-2, TIMP-1 e TIMP-2 que controles saudáveis e a utilização tópica de aprotinina aumentou ainda mais os níveis destes marcadores inflamatórios na saliva (Pietruska, Pietruski et al 2009). …”

Section: Steunclassified

“…É encontrado na literatura que citocinas pró-inflamatórias como IL-1, IL-6, TNF-α e TGF-β podem inibir a expressão do TIMP-1, e os níveis destas citocinas estão aumentadas na saliva de pacientes com DP (Pietruska, Pietruski et al 2009;Miller, Foley et al 2010).…”

Section: Steunclassified

“…Foi encontrado apenas um trabalho a quantificação do TIMP-2 em paciente com DP, e os resultados deste já foram descritas acima (Pietruska, Pietruski et al 2009 O aumento da atividade da MPO na saliva já foi descrita em pacientes com DP em relação aos seus controles (Over, Yamalik et al 1993), desta maneira, esse resultado já era esperada. Pode-se observar que existe uma tendência a diminuição da atividade da MPO após o tratamento dos pacientes com DP (p = 0,08), este fenômeno poderia ser justificado pelo fato do tratamento periodontal básico reconhecidamente diminuir o infiltrado de PMN na gengiva e na bolsa periodontal (Lindhe 2010), sugerindo que possa ter ocorrido um erro tipo 2 de estatística.…”

Section: Steunclassified

See 1 more Smart Citation

Concentrações de MMP-8, MMP-9, MPO, TIMP-1 e TIMP-2 na saliva e correlações com plasma

Meschiari¹

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases known to cleave components of the connective tissue in physiological and pathological processes. The regulation of MMP activities is done by the tissue inhibitors of metalloproteinases (TIMPs).Periodontal disease (PD) is a chronic inflammation with excessive activity of MMPs, which degrade the tooth supporting tissues.The saliva components are derived from the local blood supply, and this fluid may therefore reflect the plasma. So, the objectives of this study were: 1) to compare the levels of MMPs, TIMPs and MPO in stimulated whole saliva (SWS) and plasma of PD patients before (PB) and 3 months after (PT) the non-surgical periodontal treatment, and in healthy volunteers at baseline (CB) and 3 months after baseline (CT), and 2) to evaluate the correlations between the results found.Measurements of MMP-8, MMP-9, TIMP-1 and TIMP-2 were performed by ELISA. Gelatinolitic activity of MMP-9 forms were determined by zymography, and the MPO activity was determined by colorimetric assay.There was lower gelatinolitic activity, and lower concentrations of MMP-8 and TIMP-2 in STE on PT group compared with PB group (p <0.05). MPO activity was higher in PB compared to CB (p <0.05).Statistically significant moderate correlations were observed in all associations between MMP-9 performed by ELISA in plasma and gelatinolitic activity bands of STE: MMP-9 molecular form of 92 kDa (r = 0,37, p = 0,0017), MMP-9 molecular form of 130 kDa (r = 0,35, p = 0,003), the sum of its gelatinase activity (130 +92 kDa) (r = 0,43, p = 0,0002), gelatinase of 180 kDa (r = 0,35, p = 0,003), and the sum of total gelatinase activity (180+130+92 kDa) (r = 0,37, p = 0,002). Circulating MMP-8 levels correlate with salivary gelatinase activity bands of 92 kDa (r = 0,30, p = 0,01) and the sum of gelatinase activity (130 +92 kDa) (r = 0,24, p = 0,04). In addition, a weak correlation between gelatinase activity of plasmatic 92 kDa MMP-9 and gelatinase of 180 kDa in SWS (r= 0,26 p = 0,03) was found, and a moderate correlation between plasmatic TIMP-2 and TIMP-2 of SWS (r = 0,32, p = 0,004).The results show that the gelatinase activity of SWS may reflect the concentrations of systemic inflammatory markers such as MMP-8 and MMP-9, also the concentration of TIMP-2 in the SWS may reflect the circulating concentration of TIMP-2. The evaluation of these results suggests that there is an attenuation of some inflammatory markers analyzed in the SWS and in plasma after treatment of PD. Furthermore, there are correlations between salivary and plasma levels in some of these markers. Because saliva sampling is less invasive, more studies about the correlations between these markers in these two fluids are necessary. Key words: saliva, plasma, matrix metalloproteinases, periodontal disease. LISTA DE ABREVIATURAS, SIGLAS E SÍMBOLOS BSA -

show abstract

Assessment of aprotinin influence on periodontal clinical status and matrix metalloproteinases 1, 2 and their tissue inhibitors saliva concentrations in patients with chronic periodontitis

Cited by 16 publications

References 30 publications

Recent Advances in the Development of MMPIs and APNIs Based on the Pyrrolidine Platforms

Recent Advances in the Development of MMPIs and APNIs Based on the Pyrrolidine Platforms

An Updated Patent Therapeutic Agents Targeting MMPs

Concentrações de MMP-8, MMP-9, MPO, TIMP-1 e TIMP-2 na saliva e correlações com plasma

Contact Info

Product

Resources

About