Efeito de soluções contendo hexametafosfato de sódio e quercetina, associados ou não ao fluoreto, sobre o desgaste erosivo dentinário in vitro / Effect of sodium hexametaphosphate and quercetin, associated or not with fluoride, on dentin erosion in vitro

O objetivo do presente estudo foi investigar o efeito de soluções contendo fluoreto (F), hexametafosfato de sódio (HMP) e quercetina (QC), sozinhos ou em associação, sobre a erosão dentinária e sobre a inibição de metaloproteinases da matriz (MMPs) -2 e -9, em protocolos in vitro. Blocos de dentina radicular bovina (4 × 4 × 2 mm; n = 96), selecionados por dureza superficial, foram aleatoriamente divididos em 8 grupos experimentais (n = 12/grupo) e tratados 2×/dia (um minuto) com as seguintes soluções: (1) água deionizada (controle negativo); (2) 1100 ppm F ("F"); (3) 1,0% HMP ("HMP"); (4) 0,03% QC ("QC"); (5) F+HMP; (6) F+QC; (7) HMP+QC; e (8) F+HMP+QC. Os blocos foram submetidos a desafios erosivos 4×/dia, por 5 dias (exposição dinâmica a ácido cítrico 50 mmol.l-1 , pH 3,2, 90 s). Em seguida, foram analisados quanto à perda dentinária (perfilometria) e à perda de dureza integrada em profundidade (área sob a curva, ∆KHN). O potencial antiproteolítico das soluções contendo F, HMP e/ou QC foi analisado por zimografia. Os dados de perda dentinária (log10) foram submetidos a ANOVA um critério, seguido do teste de Tukey. Os resultados de ∆KHN (dados brutos) foram submetidos a ANOVA dois critérios, medidas repetidas, seguido do teste HolmSidak (p< 0,05). O menor desgaste erosivo foi observado no grupo F+HMP+QC. Nas menores profundidades (5-30 µm), os blocos tratados com a solução contendo F+HMP+QC apresentaram os maiores valores de ∆KHN. A análise zimográfica mostrou que todos os tratamentos promoveram atividade antiproteolítica total da MMP-2, com exceção da QC administrada sozinha (inibição de 77%). Para MMP-9, todas as soluções contendo HMP e a associação de F+QC apresentaram atividade antiproteolítica total. Conclui-se que a adição de HMP e QC a soluções contendo F levou a uma maior proteção contra a erosão dentinária, tanto em superfície (perda dentinária) quanto em relação ao conteúdo mineral do tecido remanescente (∆KHN), além de promover uma completa inibição da atividade de MMPs -2 e -9 in vitro(AU)

The aim of the present study was to investigate the effect of solutions containing fluoride (F), sodium hexametaphosphate (HMP) and quercetin (QC), alone or in association, on dentin erosion and on the inhibition of matrix metalloproteinases (MMPs) - 2 and -9, using in vitro protocols. Bovine root dentin blocks (4 × 4 × 2 mm; n = 96), selected by surface hardness, were randomly divided into 8 experimental groups (n = 12/group) and treated 2×/day (one minute) with the following solutions: (1) deionized water (negative control); (2) 1100 ppm F ("F"); (3) 1.0% HMP ("HMP"); (4) 0.03% QC ("QC"); (5) F+HMP; (6) F+QC; (7) HMP+QC; and (8) F+HMP+QC. Blocks were submitted to erosive challenges 4×/day for 5 days (dynamic exposure to 50 mmol.l-1 citric acid, pH 3.2, 90 s). They were then analyzed for dentin loss (profilometry) and integrated hardness loss in depth (area under the curve, ∆KHN). The antiproteolytic potential of solutions containing F, HMP and/or QC was analyzed by zymography. Dentin loss results (log10 transformed) were submitted to one-way ANOVA, followed by Tukey's test. ∆KHN data (raw) were submitted to two-way, repeated-measures ANOVA, followed by the Holm-Sidak test (p< 0.05). The lowest dentin erosive wear was promoted by F+HMP+QC. At the lowest depths (5-30 µm), blocks treated with F+HMP+QC showed the highest values of ∆KHN. Zymography analysis showed that all treatments completely inhibited MMP-2 activity, except for QC administered alone (77% inhibition). For MMP-9, all the solutions containing HMP or the association of F+QC promoted total antiproteolytic activity. It was concluded that the addition of HMP and QC to F solutions led to greater protection against dentin erosion, both at the surface (dentin loss) and in relation to the mineral content of the remaining tissue (∆KHN), in addition to promoting a complete inhibition of MMPs -2 and -9 activity in vitro(AU)

Planejamento, síntese, modelagem molecular e avaliação biológica de novos potenciais inibidores duais HDAC/ MMP não-hidroxamatos / Design, synthesis, molecular modeling and biological evaluation of novel potential non-hydroxamate dual HDAC/ MMP inhibitors

A inibição de alvos específicos como metaloproteinase de matriz (MMP) e histona desacetilase (HDAC) é amplamente estudada para impedir o progresso do câncer. Foi estabelecido que a inibição concomitante de MMP e HDAC é eficaz no combate de tumores sólidos e hematológicos. Ambos os alvos possuem um íon Zn2+ em seu sítio ativo, fundamental para a atividade destas enzimas. A alta afinidade dos inibidores conhecidos de MMP e de HDAC é conferida, principalmente, por um potente grupo ligante de zinco (ZBG). O ácido hidroxâmico é o ZBG mais potente conhecido atualmente, entretanto, este apresenta instabilidade farmacocinética, levando a ineficácia e genotoxicidade em testes clínicos. Frente a este contexto, o presente trabalho teve como objetivo o planejamento, síntese, modelagem molecular e avaliação biológica de novos inibidores duais MMP/HDAC não-hidroxamatos. Os compostos foram planejados utilizando estratégias de hibridação molecular, a partir de arcabouços provenientes inibidores de HDAC e MMP, gerando compostos arilsulfonamídicos com variações no tipo de ZBG inserido e na sua respectiva posição relativa na estrutura geral. Foram sintetizados sete análogos, em duas a três etapas reacionais, utilizando métodos de sulfonilação e acoplamento com agentes condensantes, partindo dos ésteres para e meta aminobenzoicos. Os rendimentos globais variaram de 25% a 55% e os produtos obtidos foram caracterizados por RMN 1H e 13C, LC/MS, CLAE e ponto de fusão. Os compostos tiveram sua atividade citotóxica avaliada em células HOG (oligodendroma) e T98G (glioblastoma), dentre os quais o 6a, que possui o ZBG 2-amino anilida, foi o mais promissor, apresentando atividade nas duas linhagens na casa de nM. Ensaios de coordenação com Fe2+ comprovaram a capacidade quelante dos análogos contendo ácido hidroxâmico e dos demais compostos citotóxicos, 4a e 4b (ZBG-2, salicilal-hidrazona), o que não foi observado para o composto 6a. Os estudos de ancoramento molecular permitiram sugerir um modo de interação para todos os ZBG propostos frente aos respectivos alvos (HDAC e MMP), sendo observado que o ZBG 4 (2-amino anilida) faria a interação de modo monodentado com a HDAC, enquanto não seria possível o encaixe no sítio catalítico da MMP. Conclui-se, portanto, que o planejamento proposto permitiu a obtenção de compostos promissores como antitumorais, e que a substituição do ácido hidroxâmico por outros ZBG fornece moléculas ativas frente a células tumorais. Entretanto, a avaliação biológica frente à MMP e HDAC é necessária para confirmar o mecanismo de ação proposto

Inhibition of specific targets such as matrix metalloproteinase (MMP) and histone deacetylase (HDAC) is extensively studied regarding arrest cancer growth. Particularly, concomitant inhibition of MMP and HDAC is effective against solid and hematologic tumors. Both targets have an ion Zn2+ at their catalytic site, which is essential for respective enzymatic activity. High affinity of known MMP and HDAC inhibitors is mainly provided by a potent zinc binding group (ZBG). Hydroxamic acid is the most potent ZBG currently known; however, it presents low pharmacokinetics stability, which results in its ineffectiveness and genotoxicity along clinical trial. So, the aim of this work comprised the design, synthesis, molecular modeling and biological evaluation of novel potential non-hydroxamate dual HDAC/ MMP inhibitors. Compounds were designed by molecular hybridation, employing scaffolds from HDAC and MMP inhibitors, which provided arylsulfonamides with variation about the ZBG type and its respective relative position in the general structure. Seven compounds were synthesized, in two to three reaction steps, through methods that comprise sulfonilation and coupling with condensing agents, using para and meta-aminobenzoic esters as starting material. Compounds showed global yields around 25-55 % and were characterized by 1H and 13C NMR, LC/MS, HPLC and melting point. Compounds were evaluated about their cytotoxicity against HOG (oligodendroma) and T98G (glioblastoma) cells, which 6a, with ZBG 2-aminobenzamide, was the most promising molecules, presenting activity against both cell lines at nM range. Coordination assays with Fe2+ proved the chelating capacity of hydroxamate analogues as well as the cytotoxic compounds, 4a and 4b (ZBG-2, salicylal-hydrazone), which was not observed about 6a. Molecular docking allowed to suggest an interaction model for all proposed ZBG with the respective targets (MMP and HDAC), showing that (ZBG-4) 2-aminobenzamide interacts with HDAC by monodentate way, but does not docks at MMP catalytic site. We conclude that the proposed design allowed obtaining promising compounds as antitumors agents, and the replacement of hydroxamic acid by other ZBG provide active molecules against tumor cells. However, biological evaluation against MMP and HDAC is necessary to confirm the proposed action mechanism

Resin-dentin bond stability of etch-and-rinse adhesive systems with different concentrations of MMP inhibitor GM1489

Abstract Enzymatic degradation of the hybrid layer can be accelerated by the activation of dentin metalloproteinases (MMP) during the bonding procedure. MMP inhibitors may be used to contain this process. Objective To evaluate the degree of conversion (DC%), dentin bond strength (µTBS) (immediate and after 1 year of storage in water), and nanoleakage of an experimental (EXP) and a commercial (SB) adhesive system, containing different concentrations of the MMP inhibitor GM1489: 0, 1 µM, 5 µM and 10 µM. Methodology DC% was evaluated by FT-IR spectroscopy. Dentin bond strength was evaluated by µTBS test. Half of beams were submitted to the µTBS test after 24 h and the other half, after storage for 1 year. From each tooth and storage time, 2 beams were reserved for nanoleakage testing. Data were analyzed using ANOVA and Tukey's test to compare means (α=0.05). Results All adhesive systems maintained the µTBS after 1 year of storage. Groups with higher concentrations of inhibitor (5 µM and 10 µM) showed higher µTBS values than groups without inhibitor or with 1 µM. The nanoleakage values of all groups showed no increase after 1 year of storage and values were similar for SB and EXP groups, in both storage periods. The inhibitor did not affect the DC% of the EXP groups, but the SB5 and SB10 groups showed higher DC% values than those of SB0 and SB1. Conclusions The incorporation of GM1489 in the adhesive systems had no detrimental effect on DC%. The concentrations of 5 µM GM1489 for SB and 5 µM or 10 µM for EXP provided higher μTBS than groups without GM1489, in the evaluation after 1 year of storage; whereas the concentration of inhibitor did not affect adhesive systems nanoleakage.

Clinical effect of Yiqi-Huoxue decoctions combined with exercise rehabilitation training for the patients with chronic heart failure / 国际中医中药杂志

Objective To study the clinical effect of Yiqi-Huoxue decoctions combined with exercise rehabilitation training for patients with chronic heart failure and its effect on serum MMP-1, TIMP-1. Methods A total of 120 patients with chronic heart failure in our hospital from February 2016 to January 2017 were enrolled in this study. The subjects were randomly divided into the control group (n=60) and the treatment group (n=60). The control group were treated with conventional treatment, and the treatment group were treated with Yiqi-Huoxue decoctions combined with exercise training. The two groups were treated for 30 days. The clinical effects of the two groups after treatment were compared. The SBP, DBP, LVESD, LVEDD and LVEF of the two groups before and after treatment were compared. The serum MMP-1, TIMP-1 of the two groups before and after treatment were compared. The adverse reaction rates of the two groups during treatment were compared. Results The total effect rate of the treatment group was 93.3％ (56/60), significantly higher than 73.3％ (44/60)of the control group (χ2=8.640, P=0.003). After treatment, the SBP (125.17 ± 13.51 mmHg vs. 140.82 ± 14.63 mmHg, t=6.087), DBP (74.36 ± 10.31 mmHg vs. 86.29 ± 11.17 mmHg, t=6.079), LVESD (41.11 ± 3.23 mm vs. 49.69 ± 4.99 mm, t=11.181) and LVEDD (57.36 ± 3.28 mm vs. 64.16 ± 4.05 mm, t=10.107) of the treatment group were significantly lower than those of the control group (P<0.05). The LVEF (69.82％ ± 5.05％ vs. 51.40％ ± 4.11％, t=21.913) of the treatment group was significantly higher than the control group (P<0.05). After treatment, the serum MMP-1 (141.52 ± 15.22 μg/L vs. 164.10 ± 16.18 μg/L, t=7.874) of the treatment group were significantly lower than those of the control group (P<0.05), and the serum TIMP-1 (3.98 ± 0.22 μg/L vs. 3.51 ± 0.16 μg/L, t=13.383) of the treatment group were significantly higher than those of the control group (P<0.05). There was no significant differences of the adverse reaction rates of the two groups during treatment (χ2=0.152, P=0.697). Conclusions The Yiqi-Huoxue decoctions combined with exercise rehabilitation training for patients with chronic heart failure showed good efficacy and low incidence of adverse reactions, can significantly improve cardiac function and the cardiac remodeling.

Imbalance in matrix metalloproteinases and matrix metalloproteinase inhibitors from diseased splenic vein and varicose great saphenous vein under high hemodynamics / 中国现代普通外科进展

Objective:To investigate the differences in matrix metalloproteinases (MMPs) and matrix metalloproteinase inhibitors (TIMPs) from diseased splenic vein (DSVs) and varicose great saphenous vein (VGSVs) under high hemodynamics.Methods:Seventy-two specimens of DSVs,normal splenic veins (SVs),VGSVs,and normal great saphenous vein (GSVs) were collected.Venous wall in the four groups,MMP-2,MMP-9,TIMP-1,and TIMP-2 protein expression were observed and MMP-2,MMP-9,TIMP-1,TIMP-2 proteins positive expression ratio and mRNA expression were determined.Results:DSVs and VGSVs in the two groups,MMP-2,MMP-9,TIMP-1,TIMP-2 proteins with clustered strong expression were observed;In DSVs group,MMP-2,MMP-9,TIMP-1,TIMP-2 protein positive expression ratio and mRNA expression were significantly increased compared with SVs group,while in VGSVs group,MMP-2,MMP-9,TIMP-1,TIMP-2 protein positive expression ratio and mRNA expression were significantly increased compared with GSVs group (P＜0.05).VGSVs/GSVs ratio was significantly increased compared with DSVs/SVs ratio (P＜0.05).Conclusion:Under high hemodynamics,the dysequilibrium of MMPs and TIMPs from splenic vein and great saphenous vein,These results may be one of the molecular mechanism in vascular remodeling.

Effect of green tea as a protective measure against dental erosion in coronary dentine

Abstract The aim of this study was to evaluate the effect of green tea as a protective measure on eroded dentin. Disks of human coronary dentin were selected based on surface hardness and randomly assigned to 3 groups (n = 10): DW - distilled water, CHX - 0.2% chlorhexidine digluconate, and GT - green tea. The disks were allowed to acquire pellicle for 2 hours and were then subjected to 3 cycles per day of demineralization (C6H8O7 0.05 M, pH 3.75, 60 s), treatment (DW or CHX or GT, 5 min) and remineralization (artificial saliva, 60 min) over a period of 3 days. Changes in the dentin were determined by loss of surface hardness (%SHL) and mechanical profilometry analysis at the end of each day. Data were analyzed by two-way ANOVA followed by Tukey’s test for %SHL and profilometry (p < 0.05). Significant reductions in dentin hardness loss were observed only for the CHX group when compared to the DW group (p < 0.05). However, there was no significant difference between the CHX and GT groups (p > 0.05). A significant difference was observed between DW and GT treatments for wear and roughness measurements (p < 0.05). The green tea extract solution was able to reduce the wear and roughness caused by dentin erosion under the conditions of this study.

Influência de agentes antiproteolíticos na resistência de união da interface dentina, adesivo e cimento resinoso / Influence of antiproteolytic agents on dentin, adhesive and luting cement interface

O objetivo deste trabalho, foi avaliar a influência de agentes antiproteolíticos, imediatamente e após 12 meses, na cimentação adesiva. Foram utilizadas as porções coronárias de 64 molares humanos hígidos. As amostras foram divididas aleatoriamente em 4 grupos, de acordo com o tratamento da dentina: CT (grupo controle); CXL (grupo clorexidina); EGCG (grupo epigalocatequina-3-galato); AT (grupo antocianina). Para a restauração, foram confeccionados cilindros em resina composta Filtek Z350 XT. Após o condicionamento ácido da dentina, as soluções antiproteolíticas foram aplicadas e mantidas sobre a superfície por 60 s, em seguida as restaurações foram cimentadas às amostras com o adesivo Adper Single Bond 2 + cimento resinoso Variolink II. Todos os grupos foram subdivididos de acordo com o tempo de armazenamento em água destilada para o ensaio mecânico: I (Imediato = após 24 h); A (Armazenado = após 12 meses). As amostras foram cortadas em palitos e submetidas ao teste de microtração. Os dados obtidos foram submetidos ao teste de ANOVA a 2 fatores, seguido do teste de Tukey (α=5%). Foram encontradas diferenças para os fatores Tratamento (p=0,03) e Armazenamento (p=0,00). Os valores em MPa de média e desvio padrão para interação entre os fatores Tratamento X Armazenamento, foram: CT.I: 42.56 (±7,60) A; EGCG.I: 39.6 (±8,99) A; CLX.I: 39.37 (±9,44) A; AT.I: 38.69 (±8,65) A; CT.A: 31.85 (±6,96) A; AT.A: 31.29 (±4,89) AB; EGCG.A: 30.94 (±9,91) AB; CLX.A: 18.68 (±4,53) B. Foram confeccionadas duas amostras adicionais de cada grupo para avaliação descritiva da microdureza knoop de subsuperfície e avaliação qualitativa da interface adesiva em MEV. Conclui-se que as soluções de EGCG e AT foram capazes de manter a estabilidade da resistência de união após 12 meses de armazenamento e que a solução de CLX afetou negativamente os valores de resistência de união comparado aos demais subgrupos(AU)

The aim of this study was to evaluate immediately and longitunally the antiproteolytic agent influence to adhesive cementation. Were used 64 coronary portion of sound human molars. The samples were divided into 4 groups according to the dentin treatment: CG (Control group); CLX (chlorhexidine group); EGCG (epigallocatechin-3- gallate group); AT (anthocyanin group). Cylindrical composite blocks were prepared using a resin composite Filtek Supreme for the restorations. The solutions were applied on the acid-etched dentin and were kept for 60 s. The resin composite blocks were cemented with the adhesive system Adper Single Bond 2 + resin cement Variolink II. All groups were subdivided according to the storage time in distilled water for mechanical testing: I (Immediate = after 24 h); S (Stored = after 12 months). Samples were cut into beams and tested in a universal testing machine at a crosshead speed of 0.5 mm/min until failure. The data were submitted to two-way ANOVA, followed by the Tukey test (α = 5%). Significant differences were found for the Treatment factor (p = 0.03) and Storage factor (p = 0.00). The mean values and standard deviation for interaction between the factors Treatment X Storage, were CG.I: 42.56 (± 7.60) A; EGCG.I: 39.6 (± 8.99) A; CLX.I: 39.37 (± 9.44) A; AT.I: 38.69 (± 8.65) A; CG.S: 31.85 (± 6.96) A; AT.S: 31.29 (± 4.89) AB; EGCG.S: 30.94 (± 9.91) AB; CLX.S: 18.68 (± 4.53) B. Two additional samples from each group were confectioned to descriptive analyses of microhardness knoop of dentin subjacent to the bonding interface and a qualitative interface evaluation with SEM (scanning electron microscope). It can be conclude that EGCG and AT solutions were able to maintain the bond strength stability after 12 months of storage and CLX solution adversely affect the bond strength values compared to other subgroups(AU)

Effects of genistein on the mRNA expressions of collagen, matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase in human embryonic skin fibroblasts / 国际中医中药杂志

Objective To investigate the effects of genistein on the mRNA expressions of collagen (Col), matrix metalloproteinase (MMP ) and tissue inhibitor of matrix metalloproteinase (TIMP) in human embryonic skin fibroblasts (CCC-ESF-1).MethodsThe cultured CCC-ESF-1cells were divided into a black control group, an estradiol group and genistein groups of different doses. The mRNA expressions of ColⅠ, ColⅢ , MMP-1, TIMP-1 and TIMP-2 were detected by RT-PCR.Results Compared with the black group, estradiol and medium dose of genistein (0.451 ± 0.037, 0.446 ± 0.047vs.0.385 ± 0.061, allP<0.05) could promote the proliferation of the CCC-ESF-1 cells, estradiol and medium dose of genistein could up-regulate the mRNA expressions of ColⅠ (0.960 ± 0.012, 0.929 ± 0.015vs.0.812 ± 0.014, allP<0.01), ColⅢ (0.892 ± 0.009, 0.824 ± 0.022vs.0.768 ± 0.025, allP<0.01), TIMP-1 (0.841 ± 0.023, 0.838 ± 0.053vs.0.751 ± 0.027, allP<0.01) and TIMP-2 (0.456 ± 0.017, 0.448 ± 0.036vs.0.381 ± 0.029, allP<0.01), and down-regulate MMP-1 mRNAexpression (0.398 ± 0.043, 0.402 ± 0.044vs.0.525 ± 0.006, allP<0.01).Conclusions Genistein could promote the proliferation of the CCC-ESF-1 cells, and that may be related with up-regulating the mRNA expressions of ColⅠ, ColⅢ , MMP-1, TIMP-1and down-regulating MMP-1 mRNA expression.

Expression of matrix aggrecanase 2 and a tissue inhibitor of metalloproteinases in degenerated intervertebral discs / 中华物理医学与康复杂志

Objective To observe the expression of aggrecanase 2 and a tissue inhibitor of metalloproteinase 3 (TIMP-3) in degenerate human lumbar intervertebral discs and their role in degeneration of the nucleus pulposus.Methods Pfirrmann classification was used to class degenerate intervertebral discs observed through MRI.They were divided into three groups:a control group (Pfirrmann grade Ⅰ-Ⅱ),a degeneration group (Pfirrmann grade Ⅲ-Ⅳ),and a severe degeneration group (Pfirrmann grade Ⅴ).A total of 45 cases accepted lumbar spine surgery for removing nucleus pulposus specimens.Each group contained 15 cases.After formalin-fixation and paraffin embedding,immunohistochemistry was used to detect aggrecanase 2 and TIMP-3 expression in the nucleus pulposus cells.Results The percentages of cells positive for aggrecanase 2 were (13.58 ± 7.76) ％,(33.48 ± 13.95) ％ and (56.00 ± 18.39) ％ in the control,degeneration and severe degeneration groups respectively.These differences had statistical significance.The percentages of cells positive for TIMP-3 were (34.78 ± 13.80) ％,(46.77 ± 10.98) ％ and (50.65 ± 16.45) ％,and these differences were again statistically significant.The aggrecanase 2/TIMP-3 ratios were also significantly different.Conclusion As the degree of degeneration of the nucleus pulposus increased,the expression of aggrecanase 2 and TIMP-3 rose,which indicates that both changes were closely connected with the degeneration.Their ratio was correlated with the degree of degeneration of the nucleus pulposus.

Effects of Topical Intranasal Doxycycline Treatment in the Rat Allergic Rhinitis Model

OBJECTIVES: Allergic rhinitis (AR) is a chronic upper respiratory tract disease that inflames the mucous membranes of the nose and occurs when circulating inflammatory cells including eosinophils and basophils migrate to and accumulate in the inflammation area by passing through the interstitium and capillary walls. To pass through these barriers, the inflammatory cells degrade extracellular matrix proteins. Matrix metalloproteinases (MMPs) released by inflammatory cells mediate the degradation of these proteins. MMPs have synthetic inhibitors and doxycycline, a tetracycline antibiotic, inhibits MMPs. This study investigated the efficiency of intranasal doxycycline in decreasing the symptoms and inflammatory cell infiltration in an animal model of AR. METHODS: AR was created in female Wistar rats by repeated intranasal challenge with ovalbumin by intraperitoneal injection. For 15 days, topical intranasal doxycycline was administered one hour before ovalbumin administration. Following intranasal administration, nasal symptoms were scored and the nasal mucosae of all rats were evaluated histopathologically. To investigate tissue changes, hematoxyline-eosin and Alcian blue/periodic acid Schiff stains were used. As well, cilia loss, goblet cell changes, vascular congestion, vascular proliferation, inflammatory cell infiltration, eosinophil infiltration and the degree of hypertrophy in chondrocytes were evaluated with light microscopy. RESULTS: Typical symptoms of AR were decreased by intranasal doxycycline administration. These effects were stable after repeated intranasal ovalbumin administration. Histological evaluation of doxycycline treated rats did not reveal typical inflammatory changes associated with AR. CONCLUSION: MMPs may have crucial functions in AR and topical intranasal doxycycline, which decreases inflammatory cell infiltration, may offer an alternative therapy for AR.

QSAR Rationale of Matrix Metalloproteinase Inhibition Activity in a Class of Carboxylic Acid Based Compounds.

The matrix metalloproteinase-13 (MMP-13) inhibitory activities of carboxylic acid based compounds, in presence and absence of bovine serum albumin (BSA), have been analyzed quantitatively in terms of chemometric descriptors. The statistically validated quantitative structure-activity relationship (QSAR) models obtained through combinatorial protocol in multiple linear regression (CP-MLR) analysis and the participated descriptors in these models provided rationales to explain the inhibitory activities of these congeners. For MMP-13 inhibition activity, the identified descriptors (BEHm1, BELm1 and BEHm8) have highlighted the role of the atomic mass in terms of the highest and lowest eigenvalues derived from Burden matrix. The positive correlation with activity suggested that their higher values are desirable in improving the activity of a compound. Additionally, the descriptor C-027 representing R-CH-X type fragment in a molecular structure advocates the absence of such type of fragment for the improved activity. On the other hand presence of RCO-N< or >N-X=X type fragment (descriptor N-072) would be beneficiary to the MMP-13 inhibitory activity. The structural features, rationalized by the descriptors MSD (Balaban’s mean square distance index), nCrHR (number of ring tertiary C (sp3), H-047 (H attached to C1(sp3)/C0(sp2)) and H-050 (H attached to heteroatom) have imparted positive impact on the MMP-13 w/BSA inhibition activity. The atomic properties such as atomic polarizability and atomic Sanderson’s electronegativity have shown their positive impact on the activity via descriptors BELp4 and GATS3e in respective eigenvalues or lag. The other descriptors, MATS1m and MATS3e, have revealed the negative influence of atomic mass and electronegativity on the of MMP-13 w/BSA inhibition activity. The results obtained from CP-MLR analysis have been supported further through partial least-squares (PLS) study.