SEARCH · PubMed Health

Results for “Matrix”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources

PubMed2005

Differential transcriptional activation of matrix metalloproteinase-2 and membrane type-1 matrix metalloproteinase by experimental deep venous thrombosis and thrombin.

OBJECTIVE: Resolution of deep venous thrombosis (DVT) is involved in the pathogenesis of postthrombotic syndrome. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that are critical in angiogenesis and tissue remodeling. We hypothesized that MMP-2 and its membrane-bound activator membrane type-1 matrix metalloproteinase (MT1-MMP) expression would be expressed and activated during the resolution of DVT. METHODS: DVT was generated by caval ligation in wild-type and MMP-2 transgenic reporter mice. Ligated and sham-operated (control) cavae were analyzed for MMP-2 transcription (beta-galactosidase activity in MMP-2 reporter mice) and MT1-MMP mRNA by real-time polymerase chain reaction. MMP-2 activity was determined by zymography, and immunohistochemical staining for beta-galactosidase and MT1-MMP protein was used to localize expression. Human umbilical vascular endothelial cells (HUVEC) were treated with 10 U/mL thrombin and MMP-2 and MT1-MMP mRNA levels and MMP-2 activity was determined. RESULTS: MMP-2 activity increased 71% (n = 5, P < .05) at day 8 in ligated vs control cavae by zymography. beta-galactosidase activity showed a 1.2-fold (n = 8, P < .05) and 1.7-fold (n = 8, P < .05) induction in MMP-2 transcription at day 3 and day 8, respectively. No significant MT1-MMP gene induction was seen at day 3 in ligated vs control cavae, but MT1-MMP mRNA was upregulated 2.5-fold (n = 8, P < .05) in ligated cavae at day 8. Immunohistochemical staining localized MMP-2 and MT1-MMP expression to the vein wall and cellular infiltrates of the thrombus. Thrombin-treated HUVEC showed differential responses of MMP-2 and MT1-MMP. Zymography of conditioned media and cell lysates illustrated a 220% (152.6 +/- 8.6 vs 69.445 +/- 5.46 pixels/unit area, n = 5, P < .05) and 150% (74.1 +/- 7.3 vs 49.2 +/- 5.7 pixels/unit area, n = 5, P < .05) increases in MMP-2 activity respectively. MMP-2 mRNA levels were downregulated 30% (0.48 +/- 0.023 vs 0.63 +/- 0.035 copies of MMP-2 mRNA/copy GAPDH, n = 5, P < .05), whereas MT1-MMP message was upregulated 250% (0.147 +/- 0.009 vs 0.059 +/- 0.005 copies of MT1-MMP mRNA/copy GAPDH, n = 5, P < .05). CONCLUSIONS: Resolution of DVT is associated with increased MMP-2 transcription and activity as well as MT1-MMP expression. Thrombin may mediate the increase in MT1-MMP noted in DVT. This is the first article studying MMP-2 and MT1-MMP transcription in DVT. These findings add DVT resolution to the class of inflammatory and fibrotic disorders in which transcriptional activation of the MT1-MMP/MMP-2 genes occurs and identify a potential therapeutic target to modulate this clinically relevant process. CLINICAL RELEVANCE: Postthrombotic syndrome remains a significant clinical problem after deep venous thrombosis (DVT), but the cellular and molecular mechanisms involved in thrombus resolution and vein wall fibrosis remain undefined. Matrix metalloproteinase (MMP) enzymes are critical to cell migration and matrix breakdown. We identify gene transcription and activity of two MMP isoforms, MMP-2 and MMP-14 (membrane type MMP 1, MT1-MMP) in the resolution phase of experimental DVT and in thrombin-treated endothelial cells. These studies define new proteases potentially important to resolution of DVT and development of postthrombotic syndrome.

Animals↗

PubMed2001

Matrix metalloproteinases: they're not just for matrix anymore!

The matrix metalloproteinases (MMPs) have been viewed as bulldozers, destroying the extracellular matrix to permit normal remodeling and contribute to pathological tissue destruction and tumor cell invasion. More recently, the identification of specific matrix and non-matrix substrates for MMPs and the elucidation of the biological consequence of cleavage indicates that perhaps MMPs should be viewed more as pruning shears, playing sophisticated roles in modulating normal cellular behavior, cell-cell communication and tumor progression.

Animals↗

PubMed2004

Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases mRNA transcripts in the bronchial secretions of asthmatics.

Asthma is a chronic inflammatory disease characterized by profound extracellular matrix changes referred to as bronchial remodelling. In this study, we evaluated matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) mRNA expression in bronchial secretions of asthmatics and correlated MMPs modulations with the lung function as a reflection of the bronchial extracellular matrix remodelling. Quantitative RT-PCR was performed on cell pellets obtained from induced sputum in order to detect the mRNAs for MMP-1, -2, -3, -8, -9, -12, -13 TIMP-1, -2, while semiquantitative RT-PCR was performed to assess the expression of MMP-7, monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-beta(1) (TGF-beta(1)). The mRNA transcripts for MMP-1, TIMP-1 and monocyte chemoattractant protein-1 (MCP-1) were increased in cell pellets of induced sputum from asthmatics when compared to controls (P<0.05), and the intensity of MMP-1 mRNA expression inversely correlated with the FEV(1) in asthmatics (r=-0.49, P<0.05). The MMP-1 mRNA/TIMP-1 mRNA ratio correlated with the levels of MCP-1 mRNA in asthmatics (r=0.47, P<0.05). There were no differences between the groups with respect to mRNA coding for MMP-2, -3, -7, -8, -9, -12, -13, -14, TIMP-2 and TGF-beta(1). We conclude that cells contained in the bronchial secretions from asthmatics express higher amounts of mRNA for MMP-1 and TIMP-1, perhaps related to an increased expression of MCP-1, which might contribute to the extracellular matrix changes observed during airway remodelling.

Adolescent↗

PubMed2000

Matricellular proteins as modulators of cell-matrix interactions: adhesive defect in thrombospondin 2-null fibroblasts is a consequence of increased levels of matrix metalloproteinase-2.

Thrombospondin 2 (TSP2)-null mice, generated by disruption of the Thbs2 gene, display a variety of connective tissue abnormalities, including fragile skin and the presence of abnormally large collagen fibrils with irregular contours in skin and tendon. In this study we demonstrate that TSP2-null skin fibroblasts show a defect in attachment to a number of matrix proteins, and a reduction in cell spreading. To investigate the molecular mechanisms responsible for these abnormal cell-matrix interactions, we compared the levels of matrix metalloproteinases (MMPs) in wild-type and mutant fibroblasts. Isolation and analysis of gelatinases from conditioned media by gelatin-agarose affinity chromatography and gelatinolytic assays demonstrated that TSP2-null fibroblasts produce a 2-fold increase in gelatinase A (MMP2) compared with wild-type cells. The adhesive defect was corrected by treatment of TSP2-null fibroblasts with soluble TSP2, with the MMP inhibitors BB94 and tissue inhibitor of metalloproteinase-2, and with a neutralizing antibody to MMP2. Moreover, stable transfection of TSP2-null fibroblasts with mouse TSP2 cDNA corrected both the adhesive defect and the altered expression of MMP2. Finally, MMP2 was shown to interact with TSP2 in a direct-binding plate assay. We conclude that TSP2 plays an important role in cell-matrix interactions, and that a deficiency in the protein results in increased levels of MMP2 that contribute to the adhesive defect in TSP2-null fibroblasts and could play a role in the complex phenotype of TSP2-null mice.

Animals↗

PubMed2002

Long-term overexpression of membrane type-1 matrix metalloproteinase and matrix metalloproteinase-2 in oleic acid-induced pancreatitis in rats.

INTRODUCTION: The matrix metalloproteinase (MMP) plays important roles in extracellular matrix turnover. However, little is known about the roles of MMP-2 and type IV collagen, and the relationship between MMP-2 and membrane type-1 matrix metalloproteinase (MT1-MMP) during progressive destruction of acinar cells in pancreatitis. AIMS AND METHODOLOGY: To examine the serial changes in the expression and activity of MMP-2 and expression of MT1-MMP and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in rats after induction of pancreatitis by intraductal infusion of oleic acid, and to determine protein concentrations by Western blot analysis and localization of type IV collagen by immunostaining. RESULTS: Gelatinolytic activity of pro-and active MMP-2 and concentrations of MT1-MMP protein, as determined by zymography and Western blot analysis, respectively, increased significantly from 6 hours to day 42 after intraductal infusion of oleic acid. TIMP-2 mRNA expression was significantly higher than that at time 0 throughout the study period, and gelatinolytic activity of active MMP-2 increased from day 3 to day 42. In addition, immunoreactivity for type IV collagen was detected as a discontinuous line along the basement membranes of ducts, vessels, tubular complexes, and acinar cells. CONCLUSION: Our findings indicate that long-term increases of gelatinolytic activity of active MMP-2 cause continuous disorganization of type IV collagen in basement membranes during progressive atrophy of pancreatic gland in oleic acid-induced pancreatitis, and that MT1-MMP and TIMP-2 work as activating factors during proMMP-2 activation. Moreover, basement membranes disorganization in the sustentacula of acinar cells and duct epithelia seems to participate in continuous derangement of acinar cells and duct epithelium.

Animals↗

PubMed1997

Stimulation of matrix metalloproteinase production by recombinant extracellular matrix metalloproteinase inducer from transfected Chinese hamster ovary cells.

Many of the tumor-associated matrix metalloproteinases that are implicated in metastasis are produced by stromal fibroblasts within or surrounding the tumor in response to stimulation by factors produced by tumor cells. In this study we transfected Chinese hamster ovary cells with putative cDNA for human extracellular matrix metalloproteinase inducer (EMMPRIN), a transmembrane glycoprotein that is attached to the surface of many types of malignant human tumor cells and that has previously been implicated in stimulation of matrix metalloproteinase production in fibroblasts. We show that these transfected cells synthesize EMMPRIN that is extensively post-translationally processed; this recombinant EMMPRIN stimulates human fibroblast production of interstitial collagenase, stromelysin-1, and gelatinase A (72-kDa type IV collagenase). We propose that EMMPRIN regulates matrix metalloproteinase production during tumor invasion and other processes involving tissue remodeling.

Animals↗

PubMed2000

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using an inorganic particle matrix for small molecule analysis

Fine metal or metal oxide powder as an alternative to conventional organic matrices in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) has been utilized successfully for lower molecular mass analytes, poly(ethylene glycol) 200 (PEG 200) and methyl stearate. Eleven kinds of particle, Al, Mn, Mo, Si, Sn, SnO2, TiO2, W, WO3, Zn and ZnO, were evaluated. The analyte was mixed with a metal or metal oxide powder (inorganic matrix) with particle diameter of tens of micrometers and liquid dispersant, followed by application to the sample target. Using a commercial MALDI-TOFMS instrument equipped with an internal 337 nm pulsed nitrogen laser, the analytes, PEG 200 and methyl stearate, were ionized as the alkali metal ion adducted molecules [M+Na]+ or [M+K]+ when the inorganic matrices Mn, Mo, Si, Sn, TiO2, W, WO3, Zn or ZnO were used. In the case of an Al matrix, PEG 200 was ionized as [M+K]+, whereas methyl stearate was ionized as [M+H]+ and [M+Al]+. These particles have potential as the matrix for MALDI. During our examination, however, only SnO2 particles did not ionize either PEG 200 or methyl stearate. Based on our protocol, when TiO2 powder was suspended with liquid paraffin, PEG 200 and methyl stearate gave their MALDI-TOF mass spectra with the lowest background noise and highest intensity. TiO2 powder seemed to be a broad potential matrix for low molecular mass polar or non-polar analytes. The results suggested that bulk particles caused rapid heating/vaporization processes and ionized analyte molecules under irradiation with a pulsed UV laser. The present method can be readily applied to obtain the low background noise MALDI-TOF mass spectra of small-sized compounds.

Journal Article↗

PubMed1997

Fiber-matrix interface studies on bioabsorbable composite materials for internal fixation of bone fractures. I. Raw material evaluation and measurement of fiber-matrix interfacial adhesion.

The objective of this study was to characterize and evaluate the performance of various fiber-matrix composite systems by studying the mechanical, thermal, and physical properties of the fiber and matrix components, and by studying the fiber-matrix interface adhesion strength using both microbond and fragmentation methods. The composites studies were poly(L-lactic acid) (PLLA) matrix reinforced with continuous fibers of either nonabsorbable AS4 carbon (C), absorbable calcium phosphate (CaP), poly(glycolic acid) (PGA), or chitin. Carbon and CaP single fibers had high Young's moduli and failed in a brittle manner. PGA and chitin single fibers had relatively lower Young's moduli and relatively higher ductility. Upon in vitro hydrolysis, CaP fibers retained 17% of their tensile strength and 39% of their Young's modulus after 12 h, PCA fibers retained 10% of their tensile strength and 52% of their Young's modulus after 16 days, and chitin fibers retained 87% of their tensile strength and 130% of their Young's modulus after 25 days. PLLA films had much lower strength and Young's moduli, but much higher ductility relative to the single fibers. Using the microbond method, the initial fiber-matrix interfacial shear strength (IFSS) of C/PLLA and CaP/PLLA microcomposites was 33.9 and 12.6 MPa, respectively. Upon in vitro hydrolysis, C/PLLA retained 49% of IFSS after 15 days and CaP/PLLA retained 46% of IFSS after 6 h. Using a fiber fragmentation method, the initial IFSS of C/PLLA, CaP/PLLA, and chitin/ PLLA was 22.2, 15.6, and 28.3 MPa, respectively. The performance of carbon fibers and C/PLLA composites was superior to the other fibers and fiber/PLLA systems, but the carbon fiber was nonabsorbable. CaP had the most suitable modulus of the absorbable fibers for fixing cortical bone fracture, but its rapid deterioration of mechanical properties and loss of IFSS limits its use. PGA and chitin fibers had suitable mechanical properties and their retention for fixing cancellous bone fractures, but likely had insufficient stiffness for applications such as bone plates for fixing cortical bone fractures.

Adhesiveness↗

PubMed1995

Matrix-assisted laser desorption/ionization mass spectrometry: improved matrix for oligosaccharides.

The aim of this article was to study the influence of different matrix molecules on the quality of matrix-assisted laser desorption/ionization mass spectra of oligosaccharides. An important criterion was the sample preparation, i.e. the crystallization process leading to the matrix from which the analytes were desorbed and investigated. Quality criteria were, among others, the resulting molecular peak intensity, the mass resolution, and the suppression of unwanted matrix peak. It was found that a mixture of 2,5-dihydroxy benzoic acid (DHB) and 1-hydroxy isoquinoline (HIC) in a weight ratio of 3:1 was best suited for the analytical investigation of oligosaccharides. In addition, this matrix mixture was found to be quite tolerant against all kinds of buffers, salts, and even additives such as sodium dodecyl sulfate (SDS). Furthermore, we determined the different affinities of the alkaline metals to the carbohydrates and found that cesium and potassium ions ionize oligosaccharides about three times better than sodium ions and therefore have an important influence on the quantum yield.

Carbohydrate Sequence↗

PubMed2004

Small molecule matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using a polymer matrix.

We have employed a light-absorbing electrically conductive polymer as a matrix to determine the molecular mass of small organic molecules using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. This method, which is in contrast to the usual MALDI strategy for matrix selection in which a small molecule matrix is used with a high molecular mass analyte, addresses the problem of matrix interference which limits the usefulness of MALDI-TOF for small molecule analysis. Use of negative ion mode offers advantages for this application. Using this approach, we have obtained clean molecular ion mass spectra of small organic molecules in the mass range 100-300 Da.

Journal Article↗

PubMed2002

Ready-made matrix-assisted laser desorption/ionization target plates coated with thin matrix layer for automated sample deposition in high-density array format.

The methodology for ready-made matrix-assisted laser desorption/ionization (MALDI) target plates covered with an optimized thin layer consisting of matrix and nitrocellulose has been developed. Piezoelectric microdispensing enabled sample depositions in a high-density array format of 2000 sample depositions on a conventionally sized target plate (45 x 47 mm). The sample depositions were made reproducibly in a fully automated mode by using an in-house developed computer-controlled piezoelectric flow-through microdispenser. Additionally, the piezoelectric technique facilitated significant analyte enrichment that increased the detection sensitivity. The MS signal was obtained rapidly, generally within ten laser pulses. An airbrush device was used to generate a fine spray of matrix and nitrocellulose dissolved in acetone. The acetone evaporated instantly when reaching the target plate leaving the entire surface with a thin and uniform matrix/nitrocellulose coating consisting of very small crystals of matrix embedded in the nitrocellulose. These crystals acted as a seed-layer on subsequent analyte depositions, rendering homogeneous sample spots when using alpha-cyano-4-hydroxycinnamic acid (CHCA) as matrix. The relative standard deviation of the signal intensity between spots was (20-30)% (n = 30). The detection sensitivity was improved by restricting the sample spot diameter to 300 microm. The spot size was affected by the deposition rate and the evaporation rate of the dispensed sample volume. Mass spectra of a 25-amol peptide mixture deposition were successfully recorded.

Journal Article↗

PubMed1990

Maintenance of embedded pig pancreatic pseudo-islets in a collagen gel matrix: study of the effect of hydrocortisone, a collagenase inhibitor, and nicotinamide on collagenolysis and the morphogenesis of pancreatic islet-cells in collagen gel matrix.

We describe a method for maintaining neonatal pig pancreatic isletlike cell clusters (as pseudo-islets) embedded in a collagen gel matrix for long periods. The pseudo-islets were formed from single cells of pig pancreas maintained in a suspension culture and then embedded in pepsin-solubilized type I collagen. When the pseudo-islets were cultured in the collagen matrix, the amount of collagen in the culture decreased gradually during the culture period as soluble hydroxyproline-containing material accumulated in the medium. A low concentration of collagen (0.16%) degraded the collagen gels more rapidly than did high concentrations of collagen (0.64%). The degradation of collagen depended both on the number of pseudo-islets embedded in the gel matrix and on the culture conditions used to maintain them. With added nicotinamide, the accumulation of hydroxyproline decreased in the medium and the structure of the gel matrix was well maintained. Hydrocortisone or a specific inhibitor of collagenase did not decrease the solubilization of embedded pseudo-islet cultures and did not help to maintain their structure. These observations indicate the possible utility of long-term maintenance of pseudo-islets in collagen gel matrix in the presence of nicotinamide.

Animals↗

PubMed1983

Matrix Gla protein, a new gamma-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone.

A new protein has been isolated from CaCl2/urea extracts of demineralized bovine bone matrix. This protein has five to six residues of the vitamin K-dependent amino acid, gamma-carboxyglutamic acid (Gla), and we have accordingly designated it matrix Gla protein. Matrix Gla protein is a 15,000 dalton protein whose amino acid composition includes a single disulfide bond. The absence of 4-hydroxyproline in matrix Gla protein demonstrates that it is not a precursor to bone Gla protein, 5,800 dalton protein which has a residue of 4-hydroxyproline at position 9 in its sequence. Matrix Gla protein also does not cross-react with antibodies raised against bone Gla protein.

1-Carboxyglutamic Acid↗

PubMed2005

Combination of analyte protectants to overcome matrix effects in routine GC analysis of pesticide residues in food matrixes.

Analyte protectants were previously defined as compounds that strongly interact with active sites in the gas chromatographic (GC) system, thus decreasing degradation, adsorption, or both of coinjected analytes. In this study, we evaluated various combinations of promising analyte protectants for the volatility range of GC-amenable pesticides using GC/quadrupole mass spectrometry (MS) and 1-microL hot splitless injection for sample introduction. A mixture of ethylglycerol, gulonolactone, and sorbitol (at 10, 1, and 1 mg/mL, respectively, in the injected samples) was found to be the most effective in minimizing losses of susceptible analytes and significantly improving their peak shapes (due to reduction of peak tailing). When added to final sample extracts and matrix-free calibration standards alike, these analyte protectants induced a similar response enhancement in both instances, resulting in effective equalization of the matrix-induced response enhancement effect even after a large number of fruit and vegetable extract injections. As compared to matrix-matched standardization, the analyte protectant approach offers a more convenient solution to the problems associated with calibration in routine GC/MS analysis of pesticide residues and possibly other susceptible analyte types in diverse samples. Moreover, the use of analyte protectants also substantially reduced another adverse matrix-related effect caused by gradual build-up of nonvolatile matrix components in the GC system, thus improving ruggedness and, consequently, reducing need for frequent maintenance.

Biphenyl Compounds↗

PubMed1989

Inhibition of mitochondrial-matrix inorganic pyrophosphatase by physiological [Ca2+], and its role in the hormonal regulation of mitochondrial matrix volume.

1. The pyrophosphatase activity in cytosolic and mitochondrial fractions of rat liver was 1.7 and 0.26 units/mg of protein respectively when assayed at 37 degrees C in the presence of physiological [Mg2+] (0.3 mM). 2. Approx. 80% of the mitochondrial pyrophosphatase was inaccessible to extramitochondrial PPi, of which 40% represented soluble matrix enzyme (0.38 unit/mg of matrix protein). 3. Ca2+ inhibited the soluble matrix enzyme; the effective K0.5 for inhibition increased as [Mg2+], an essential cofactor of the enzyme, increased. Measured values were 0.39, 1.15, 3.7, 8.3 and 12.5 microM at 0.04 mM-, 0.1 mM-, 0.3 mM-, 0.6 mM- and 1 mM-Mg2+ respectively. 4. The data were analysed by a kinetic model similar to that for yeast pyrophosphatase, which assumes the substrate to be MgPPi (Km 5 microM) with Mg2+ also activating at an additional site (K0.5 23 microM). Ca2+ inhibits through the formation of CaPPi, a strong competitive inhibitor (Ki 0.067 microM). 5. Heart mitochondria also contain a soluble matrix pyrophosphatase of similar activity to that of liver mitochondria and with the same sensitivity to [Ca2+]. 6. The data provide an explanation for the increase in mitochondrial PPi, mediated by Ca2+, which is responsible for the increase in matrix volume induced by gluconeogenic hormones [Davidson & Halestrap (1988) Biochem. J. 254, 379-384].

Animals↗

PubMed2006

Visual field testing with the new Humphrey Matrix: a comparison between the FDT N-30 and Matrix N-30-F tests.

PURPOSE: To determine if the N-30-F test with the new Humphrey Matrix instrument is comparable to the traditional frequency-doubling technology (FDT) N-30 test. METHODS: A sample of 47 eyes from 47 patients (five normal subjects, 27 with ocular hypertension and 15 with glaucoma) underwent visual field (VF) testing with standard automated perimetry, and with FDT, using the FDT N-30 program, and the Matrix N-30-F program (using the same 19 tested points, full-threshold strategy, but with an enhanced algorithm to reduce testing time). The plots, mean deviation (MD), pattern standard deviation (PSD), defect locations and test time were compared. RESULTS: The agreement between the two tests was shown to be good, except for subjects with large VF defects, in which greater PSD values were observed with the FDT test, whereas the Matrix test gave a higher MD and number of abnormal test locations in the total deviation plot. A lack of agreement was also found for the number of abnormal test locations on the pattern deviation plot at any VF loss severity level. The test time for the Matrix test was significantly shorter. CONCLUSION: The FDT N-30 and Matrix N-30-F tests proved to be comparable in cases of early to moderate VF defects.

Adult↗

PubMed2004

Comparative in vitro and in vivo evaluation of matrix, osmotic matrix, and osmotic pump tablets for controlled delivery of diclofenac sodium.

The aim of this investigation was preparation and comparative evaluation of fabricated matrix (FM), osmotic matrix (OM), and osmotic pump (OP) tablets for controlled delivery of diclofenac sodium (DS). All formulations were evaluated for various physical parameters, and in vitro studies were performed on USP 24 dissolution apparatus II in pH 7.4 buffer and distilled water. In vivo studies were performed in 6 healthy human volunteers; the drug was assayed in plasma using HPLC, and results were compared with the performance of 2 commercial tablets of DS. Various pharmacokinetic parameters (ie, C(max), T(max), area under the curve [AUC(0-24)], and mean residence time) and relative bioavailability were compared. All fabricated formulations showed more prolonged and controlled DS release compared with commercial tablets studied. The OM and OP tablets, however, performed better than the matrix tablets. The rate and extent of drug release from FM1 matrix tablets (single polymer) was significantly different from that of FM2 (admixed polymers). Type of porosigenic agents and osmogens also influenced the drug release. Analysis of in vitro data by regression coefficient analysis revealed zero-order release kinetics for OM and OP tablets, while FM tablets exhibited Higuchi kinetics. In vivo results indicated prolonged blood levels with delayed peak and improved bioavailability for fabricated tablets compared to commercial tablets. It was concluded that the osmotic matrix and osmotic pump tablets could provide more prolonged, controlled, and gastrointestinal environmental-independent DS release that may result in an improved therapeutic efficacy and patient compliance.

Adult↗

PubMed2000

Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP).

Matrix metalloproteinase (MMP)-19 and MMP-20 (enamelysin) are two recently discovered members of the MMP family. These enzymes are involved in the degradation of the various components of the extracellular matrix (ECM) during development, haemostasis and pathological conditions. Whereas MMP-19 mRNA is found widely expressed in body tissues, including the synovium of normal and rheumatoid arthritic patients, MMP-20 expression is restricted to the enamel organ. In this study we investigated the ability of MMP-19 and MMP-20 to cleave two of the macromolecules characterising the cartilage ECM, namely aggrecan and the cartilage oligomeric matrix protein (COMP). Both MMPs hydrolysed aggrecan efficiently at the well-described MMP cleavage site between residues Asn(341) and Phe(342), as shown by Western blotting using neo-epitope antibodies. Furthermore, the two enzymes cleaved COMP in a distinctive manner, generating a major proteolytic product of 60 kDa. Our results suggest that MMP-19 may participate in the degradation of aggrecan and COMP in arthritic disease, whereas MMP-20, due to its unique expression pattern, may primarily be involved in the turnover of these molecules during tooth development.

Aggrecans↗