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Elastase
Kinds of Elastase Terms modified by Elastase Selected AbstractsGranulocyte elastase, matrix metalloproteinase-8 and prostaglandin E2 in gingival crevicular fluid in matched clinical sites in smokers and non-smokers with persistent periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 5 2002B. Söder Abstract Background/aims: Smokers with persistent periodontitis may have granulocytes with impaired function. This study aimed to determine the levels of granulocyte elastase, matrix metalloproteinase-8 (MMP-8) and prostaglandin E2 (PGE2) in gingival crevicular fluid (GCF) in smokers and non-smokers with persistent periodontitis. Methods: We analyzed GCF from 70 matched sites in 29 periodontitis and 6 gingivitis sites in 34 subjects, 17 smokers, and 17 non-smokers. We also analyzed separately GCF from 28 of these subjects, 14 smokers and 14 non-smokers in 14 matched periodontitis sites. The following measurements were made: elastase complexed to ,1 -antitrypsin (EA-,1AT) and MMP-8 with ELISA, functional elastase with a chromogenic substrate, and PGE2 with radioimmunoassay (125I RIA). The significance of the findings was determined with Mann-Whitney test. Results: In the 29 matched periodontitis sites, smokers had significantly more functional elastase (p<0.005) and more EA-,1AT (p<0.05) than non-smokers. In the 14 matched periodontitis sites in 14 smokers and 14 non-smokers, the former had significantly more functional elastase than the latter (p<0.001). A significant correlation was found between EA-,1AT and MMP-8 in smokers (p<0.05) and non-smokers (p<0.001) and a positive correlation between levels of functional elastase and MMP-8 in non-smokers (r2=0.98; p<0.001). Conclusions: Granulocyte function seems to be impaired in smokers with persistent periodontitis. The cells react to the bacterial challenge by releasing serine proteases, which reflect the degradation of connective tissue. The risk of progression of the disease is therefore higher in smokers with persistent periodontitis than in non-smokers. Zusammenfassung Hintergrund, Ziele: Raucher mit bestehender Parodontitis haben möglicherweise Granulozyten mit beeinträchtigter Funktion. Diese Studie zielt auf die Bestimmung der Levels von Granulozytenelastase, Matrix-Metalloproteinase-8 (MMP-8) und Prostaglandin E2 (PGE2) in der krevikulären gingivalen Flüssigkeit (GCF) bei Rauchern und Nichtrauchern mit bestehender Parodontitis. Methoden: Wir analysierten GCF von 70 entsprechenden Flächen bei 29 Parodontitis und 6 Gingivitisflächen von 34 Personen, 17 Rauchern und 17 Nichtrauchern. Wir analysierten zusätzlich getrennt die GCF von 28 dieser Personen: 14 Raucher und 14 Nichtraucher von 14 entsprechenden parodontalen Flächen. Die folgenden Messungen wurden vorgenommen: Elastasekomplex zu ,1 -Antitrypsin (EA-,1AT) und MMP-8 mit ELISA, funktionelle Elastase mit chromogenem Substrat und PGE2 mit Radioimmunoassay (125I RIA). Die Signifikanz der Ergebnisse wurde mit dem Mann-Whitney Test bestimmt. Ergebnisse: In den 29 entsprechenden parodontalen Flächen hatten die Raucher signifikant mehr funktionelle Elastase (p<0.005) und mehr EA-,1At (p<0.05) als Nichtraucher. Bei den 14 entsprechenden parodontalen Flächen der 14 Raucher und 14 Nichtraucher hatten die ersten signifikant mehr funktionelle Elastase als die letzteren (p<0.001). Eine signifikante Korrelation wurde zwischen EA-,1AT und MMP-8 bei Rauchern (p<0.05) und Nichtrauchern (p<0.001) gefunden und eine positive Korrelation zwischen den Levels der funktionellen Elastase und MMP-8 bei Nichtrauchern (r2=0.98; p<0.001) festgestellt. Schlussfolgerungen: Die Granulozytenfunktion scheint bei Rauchern mit bestehender Parodontitis beeinträchtigt zu sein. Die Zellen reagieren auf die bakterielle Herausforderung durch Freisetzung von Serinproteasen, die die Degradation von Bindegewebe reflektiert. Das Risiko einer Progression dieser Erkrankung ist deshalb bei Rauchern mit bestehender Parodontitis höher als bei Nichtrauchern. Résumé Origine, but: Les fumeurs avec parodontite persistante pourraient avoir des granulocytes ayant des fonctions déréglées. Cette étude a eu pour but de déterminer les niveaux d'élastase granulocytaire, de la métallo-protéinase-8 de la matrice (MMP-8) et de la prostaglandine E2 (PGE2) dans le fluide créviculaire gingival (GCF) chez les fumeurs et les non-fumeurs avec parodontite persistante. Méthodes: Le GCF a été prélevé de 70 sites équivalents dans 29 parodontites et 6 sites avec gingivite chez 34 sujets, 17 fumeurs et 17 non-fumeurs. Le GCF de 28 de ces sujets a été analysé séparément, 14 fumeurs et 14 non-fumeurs dans 14 sites équivalents du point de vue parodontite. Les mesures suivantes ont été relevées: l'élastase avec ,1 -antitrypsine (EA-,1AT) et MMP-8 par ELISA, l'élastase fonctionnelle avec un substrat chromogénique, et PGE2 avec un essai radio-immunitaire (125I RIA). La signification de ces découvertes a été par l'utilisation du test de Mann-Whitney. Résultats: Dans les 29 sites équivalents, les fumeurs avaient significativement plus d'élastase functionnelle (p<0.005) et plus de EA-,1AT (p<0.05) que les non-fumeurs. Dans les 14 sites équivalents du point de vue parodontite, les 14 fumeurs avaient significativement plus d'élastase fonctionnelle que les 14 non-fumeurs (p<0.001). Une relation significative a étéétablie entre EA-,1AT et MMP-8 chez les fumeurs (p<0.05) et les non-fumeurs (p<0.001) et une relation positive entre les niveaux d'élastase fonctionnelle et de MMP-8 chez les non-fumeurs (r2=0.98; p<0.001). Conclusions: La fonction granulocytaire semble être altérée chez les fumeurs avec parodontite persistante. Les cellules réagissent à l'attaque bactérienne en relâchant des protéases sérine, ce qui démontre une dégradation du tissu conjonctif. Le risque de progression de la maladie est ainsi plus élevé chez les fumeurs avec parodontite persistante que chez les non-fumeurs. [source] Inhibition of elastase activity by essential oils in vitroJOURNAL OF COSMETIC DERMATOLOGY, Issue 4 2002Masahiro Mori Summary, Background, Essential oils are widely used, for example in aromatherapy and aroma massage. In aroma massage, essential oil, diluted with vegetable oil, is rubbed onto the skin. Components of essential oil penetrate into the skin and have an influence on the dermis. Elastase is an enzyme which degenerates dermal elastin. Elastase activity is believed to contribute to cutaneous wrinkling and ageing. Aim, To investigate the inhibitory effect of essential oils on elastase activity. Methods, Inhibition of elastase activity by various essential oils was assessed using two elastase enzymes: porcine pancreatic elastase (PPE) and human neutrophil elastase (HNE). Results, Elastase activity was inhibited by various essential oils, especially by those oils derived from lemons, juniper and grapefruit. Although the specific inhibitory component was not determined, lemon oil had the greatest inhibitory effect on PPE. Some essential oils also inhibited HNE. Conclusions, These studies demonstrate a possible rationale for the use of essential oil massage as a preventive treatment for cutaneous wrinkling and ageing. [source] Caspase 1,independent activation of interleukin-1, in neutrophil-predominant inflammationARTHRITIS & RHEUMATISM, Issue 12 2009Monica Guma Objective Interleukin-1, (IL-1,) is a key cytokine linked to the pathogenesis of acute arthritis. Caspase 1, neutrophil elastase, and chymase all process proIL-1, to its biologically active form. This study was undertaken to examine the potential contributions of each of these proteases in experimental models of inflammatory arthritis. Methods Caspase 1,deficient (Casp1,/,) and wild-type (WT) mice were tested for their response to arthritogenic K/BxN serum transfer for induction of arthritis or injection of monosodium urate monohydrate (MSU) crystals for induction of peritonitis. All mice were prophylactically treated with inhibitors of neutrophil elastase or chymase. Arthritic paws were tested for the presence of IL-1, protein by enzyme-linked immunosorbent assay and Western blotting. Neutrophils and mast cells from WT and mutant mice were tested for their ability to secrete IL-1, after in vitro stimulation, in the presence of protease inhibitors. Results Casp1,/, and WT mice developed paw swelling to the same extent in the K/BxN serum transfer,induced arthritis model. MSU crystal injection into Casp1,/, mice also resulted in neutrophil influx and production of measurable peritoneal IL-1, protein. Both of these responses were attenuated with neutrophil elastase inhibitors. K/BxN serum transfer,induced arthritis was also reduced by treatment with a chymase inhibitor. Casp1,/, neutrophils and mast cells, when exposed to MSU crystals, secreted similar amounts of IL-1, protein upon in vitro stimulation with lipopolysaccharide, albeit at lower levels than that secreted by WT cells. Elastase and chymase inhibitors reduced the amount of IL-1, released by these cells. Conclusion The production of IL-1, by neutrophils and mast cells is not exclusively dependent on caspase 1, and other proteases can compensate for the loss of caspase 1 in vivo. These pathways might therefore compromise the caspase 1,targeted therapies in neutrophil-predominant arthritis. [source] New Peptolides from the Cyanobacterium Nostoc insulare as Selective and Potent Inhibitors of Human Leukocyte ElastaseCHEMBIOCHEM, Issue 16 2008Christian Mehner Abstract Eight new cyanopeptolins (insulapeptolides A,H) were obtained from the cyanobacterium Nostoc insulare. Their isolation was guided by their bioactivity toward the target enzyme human leukocyte elastase, molecular biological investigations, and MALDI-TOF analysis. These peptides are selective inhibitors of human leukocyte elastase with activities in the nanomolar range. Insulapeptolide D (4) was the most potent compound with an IC50 value of 85 nM (Ki value of 36 nM). [source] Inhibition of Human Leukocyte Elastase by Brunsvicamides,A,C: Cyanobacterial Cyclic PeptidesCHEMMEDCHEM, Issue 9 2009Mihiret Cyanobacterial cyclic peptides, brunsvicamides,A,C, were evaluated as inhibitors of human leukocyte elastase (HLE), and subsequently tested against a panel of proteases and two serine esterases. Brunsvicamides,A,C were found to be highly selective for HLE. [source] Interferon-, in healthy subjects: selective modulation of inflammatory mediatorsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2001J. De Metz Background It is suggested that interferon-, (IFN-,), like other cytokines, is a mediator in the host inflammatory response, which could be of importance in the pathophysiology of sepsis. The role of IFN-, in human host inflammatory responses, however, has not been studied. Design In a placebo-controlled trial we studied the acute effects of IFN-, administration on host inflammatory mediators in healthy men: i.e. the cytokine/chemokine cascade system, acute-phase proteins, activation markers of the innate cellular immunity and coagulation/fibrinolysis parameters. Results IFN-, increased plasma levels of interleukin-6 (IL-6), IL-8 and IFN-,-inducible protein-10 (IP-10) (P < 0·05), but did not affect plasma levels of other cytokines (IL-4, IL-10, tumour necrosis factor-,, IL-12p40/p70). Plasma concentrations of C-reactive protein and secretory phospholipase A2 both increased (P < 0·05). Plasma levels of the leucocyte activation marker elastase-,1,antitrypsin complexes increased after IFN-, administration (P < 0·05), IFN-, increased the percentage of high-affinity Fc,-receptor (Fc,RI) -positive neutrophils (P < 0·05), but did not affect the mean fluorescence intensity of Fc,RI on neutrophils. Procoagulant and profibrinolytic effects of IFN-, were evidenced by increased plasma levels of prothrombin fragment F1 + F2, tissue-plasminogen activator and plasmin-,2,antiplasmin complexes (P < 0·05). Conclusion We conclude that IFN-, selectively affects host inflammatory mediators in humans. [source] Reduction of different inflammatory cell types of the innate immune system in psoriatic skin during etanercept treatmentEXPERIMENTAL DERMATOLOGY, Issue 8 2010Marjan De Groot Please cite this paper as: Reduction of different inflammatory cell types of the innate immune system in psoriatic skin during etanercept treatment. Experimental Dermatology 2010; 19: 754,756. Abstract:, To investigate whether specific markers for innate immunity would diminish with successful treatment in psoriasis, we analyzed lesional and non-lesional skin biopsies taken from patients with moderate to severe psoriasis during 12 weeks of treatment with etanercept in correlation with the clinical response. In the clinical responders (PASI reduction >50%), all markers (CD3, CD68, CD161, elastase, BDCA-2, TNF-,) showed a decline during treatment, indicating a pivotal role for innate immunity in the pathogenesis of psoriasis. [source] Kinetic and crystallographic analysis of complexes formed between elastase and peptides from ,-caseinFEBS JOURNAL, Issue 10 2001Penny A. Wright Human ,-casomorphin-7 (NH2 -Tyr-Pro-Phe-Val-Glu-Pro-Ile-CO2H) is a naturally occurring peptide inhibitor of elastase that has been shown to form an acyl-enzyme complex stable enough for X-ray crystallographic analysis at pH 5. To investigate the importance of the N-terminal residues of the ,-casomorphin-7 peptide for the inhibition of elastase, kinetic and crystallographic analyses were undertaken to identify the minimum number of residues required for effective formation of a stable complex between truncated ,-casomorphin-7 peptides and porcine pancreatic elastase (PPE). The results clearly demonstrate that significant inhibition of PPE can be effected by simple tri-, tetra-and pentapeptides terminating in a carboxylic acid. These results also suggest that in vivo regulation of protease activity could be mediated via short peptides as well as by proteins. Crystallographic analysis of the complex formed between N -acetyl-Val-Glu-Pro-Ile-CO2H and PPE at pH 5 (to 1.67 Å resolution) revealed an active site water molecule in an analogous position to that observed in the PPE/,-casomorphin-7 structure supportive of its assignment as the ,hydrolytic water' in the deacylation step of serine protease catalysis. [source] Effects of clinical isolates of Pseudomonas aeruginosa on Staphylococcus epidermidis biofilm formationFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2010Maria Pihl Abstract Pseudomonas aeruginosa is often found in chronic infections, including cystic fibrosis lung infections and those related to chronic wounds and venous ulcers. At the latter sites, P. aeruginosa can be isolated together with Staphylococcus epidermidis, and we have therefore explored the effect of clinical isolates and laboratory strains of P. aeruginosa strains on colonization by S. epidermidis in dual-species biofilms. Biofilm formation was assayed using 16S rRNA FISH and confocal laser scanning microscopy. Among the six P. aeruginosa strains tested, one particular strain, denoted 14:2, exerted a significant inhibitory effect, and even after 6 h, S. epidermidis levels in dual-species biofilms were reduced by >85% compared with those without P. aeruginosa. Interestingly, strain 14:2 was found to be negative for classical virulence determinants including pyocyanin, elastase and alkaline protease. Therefore, we suggest that less virulent phenotypes of P. aeruginosa, which may develop over time in chronic infections, could counteract colonization by S. epidermidis, ensuring persistence and dominance by P. aeruginosa in the host micro-habitat. Further studies are required to explain the inhibitory effect on S. epidermidis, although extracellular polysaccharides produced by P. aeruginosa might play a role in this phenomenon. [source] Decreased virulence of a strain of Pseudomonas aeruginosa O12 overexpressing a chromosomal type 1 ,-lactamase could be due to reduced expression of cell-to-cell signaling dependent virulence factorsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2000Françoise Ramisse Abstract Pseudomonas aeruginosa produces a large variety of virulence factors and is characterized by its capacity to rapidly develop resistance when exposed to antibiotics. In order to evaluate a possible correlation between acquired resistance to antibiotics and virulence, we examined the virulence of four isogenic variants of P. aeruginosa O12 that differ in their resistance phenotypes to various ,-lactam antibiotics in a mouse model of acute pneumonia. Strains overproducing a chromosomal type 1 ,-lactamase were less virulent in both immunocompetent and immunosuppressed animals. Whereas the production of the exopolysaccharide alginate was similar between the four strains, extracellular virulence factors (elastase, rhamnolipid) that are controlled by the cell-to-cell signaling system circuit were detected in reduced amounts in the supernatant of the two isolates overproducing type 1 ,-lactamase. These results suggest that strains overexpressing the chromosomal type 1 ,-lactamase could be less virulent because of a reduction of cell-to-cell signaling dependent virulence factor production. [source] Neutrophil elastase in pressure ulcer fluid degrades fibronectin in the exudatesGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 3 2004Shingo Ai Background: Pressure ulcers are classified as chronic wounds, which do not heal in a timely fashion. Fibronectin is condensed in granulation tissue, and essential glycoprotein of wound healing. It has been proposed that fibronectin degradation may be involved in delaying wound healing. We have investigated whether pressure ulcer fluid (PUF) contains degraded fibronectin. In addition, we tried to identify the proteinase which contributes to fibronectin degradation in PUF. Methods: Fibronectin degradation and the presence of neutrophil elastase (NE) in PUF were determined by immunoblot analysis. Fibronectin degradation activity in PUF was determined in the presence of various proteinase inhibitors. NE activity was assessed using NE specific substrate. Results: Immunoblot analysis revealed that degraded fibronectin was observed in PUF samples but not in acute wound fluid (AWF). The PUF contained a proteinase capable of degrading freshly added fibronectin and its activity in PUF was blocked by a broad-spectrum serine proteinase inhibitor or sivelestat, a specific neutrophil elastase inhibitor, but not by metalloproteinase and cysteine proteinase inhibitors. Immunoblot analysis of PUF using an antineutrophil elastase antibody revealed that neutrophil elastase was detected as three bands at molecular weights of ,30 kDa, ,38 kDa, and ,54 kDa, indicating that neutrophil elastase in the exudates existed not only as free monomers, but also in polymers or complexes with other molecules. Conclusion: These results suggest that PUF contains a high level of neutrophil elastase which may be involved in the delay of the healing of pressure ulcer through the fibronectin degradation. [source] Protective role of osteopontin in endodontic infectionIMMUNOLOGY, Issue 1 2010Susan R. Rittling Summary Endodontic infections are polymicrobial infections resulting in bone destruction and tooth loss. The host response to these infections is complex, including both innate and adaptive mechanisms. Osteopontin (OPN), a secreted, integrin-binding protein, functions in the regulation of immune responses and enhancement of leucocyte migration. We have assessed the role of OPN in the host response to endodontic infection using a well-characterized mouse model. Periapical bone loss associated with endodontic infection was significantly more severe in OPN-deficient mice compared with wild-type 3 weeks after infection, and was associated with increased areas of inflammation. Expression of cytokines associated with bone loss, interleukin-1, (IL-1,) and RANKL, was increased 3 days after infection. There was little effect of OPN deficiency on the adaptive immune response to these infections, as there was no effect of genotype on the ratio of bacteria-specific immunoglobulin G1 and G2a in the serum of infected mice. Furthermore, there was no difference in the expression of cytokines associated with T helper type 1/type2 balance: IL-12, IL-10 and interferon-,. In infected tissues, neutrophil infiltration into the lesion area was slightly increased in OPN-deficient animals 3 days after infection: this was confirmed by a significant increase in expression of neutrophil elastase in OPN-deficient samples at this time-point. We conclude that OPN has a protective effect on polymicrobial infection, at least partially because of alterations in phagocyte recruitment and/or persistence at the sites of infection, and that this molecule has a potential therapeutic role in polymicrobial infections. [source] Momordica charantia trypsin inhibitor II inhibits growth and development of Helicoverpa armigeraINSECT SCIENCE, Issue 5 2009Manasi Alok Telang Abstract, Bitter gourd (Momordica charantia L.) seeds contain several squash-type serine proteinase inhibitors (PIs), which inhibit the digestive proteinases of the polyphagous insect pest Helicoverpa armigera. In the present work isolation of a DNA sequence encoding the mature peptide of a trypsin inhibitor McTI-II, its cloning and expression as a recombinant protein using Pichia pastoris have been reported. Recombinant McTI-II inhibited bovine trypsin at 1: 1 molar ratio, as expected, but did not inhibit chymotrypsin or elastase. McTI-II also strongly inhibited trypsin-like proteinases (81% inhibition) as well as the total proteolytic activity of digestive proteinases (70% inhibition) from the midgut of H. armigera larvae. The insect larvae fed with McTI-II-incorporated artificial diet suffered over 70% reduction in the average larval weight after 12 days of feeding. Moreover, ingestion of McTI-II resulted in 23% mortality in the larval population. The strong antimetabolic activity of McTI-II toward H. armigera indicates its probable use in developing insect tolerance in susceptible plants. [source] ,1 -antitrypsin prevents polymorphonuclear leucocyte-elastase effects on spermatozoa qualityINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2010J. Leßig Summary Elevated levels of polymorphonuclear leucocyte (PMN)-derived elastase, which is suggested as marker for inflammations in the male genital tract, correlate well with spermatozoa deterioration. PMN elastase caused a time- and concentration-dependent (up to a elastase concentration of 0.5 ,g/mL) externalization of phosphatidylserine and intercalation of propidium iodide on human spermatozoa. There are apparently a limited number of target sites for elastase on spermatozoa surface, because the further enhancement of elastase amount did not fasten alterations in spermatozoa parameters. Analysis of flow cytometry data revealed that most spermatozoa were in a necrotic state after an exposure with elastase for 22 h. Some apoptotic cells were only detected at shorter incubation periods. Seminal plasma prevented in a concentration-dependent manner the PMN elastase-mediated loss of vitality of spermatozoa. We detected by blotting techniques large amounts of ,1 -antitrypsin in seminal plasma. This antiproteinase is known to inactivate elastase at inflammatory sites. Increasing concentrations of ,1 -antitrypsin prevented gradually spermatozoa deterioration induced by elastase. Thus, ,1 -antitrypsin contributes to an efficient protease/antiproteinase balance in seminal plasma. A disturbed balance will promote the development of chronic inflammations which can also be the reason for male infertility problems. [source] Impact of cyclins E, neutrophil elastase and proteinase 3 expression levels on clinical outcome in primary breast cancer patients,INTERNATIONAL JOURNAL OF CANCER, Issue 11 2006Christine Desmedt Abstract Uncontrolled cell proliferation is one of the hallmarks of cancer and the transition from the G1 to S phase is the most commonly reported cell cycle abnormality in tumors. It has been shown that the oncogenic activity of G1 cyclin E (CCNE) can be amplified by generating hyperactive low molecular weight forms (LMW) through elastase-mediated proteolytic processing. Neutrophil elastase (NE) and proteinase 3 (PR3) are 2 proteases that are aberrantly expressed in breast cancer cells and seem to be involved in cell proliferation. In this study, we evaluated the effect of the expression of these 2 proteases in addition to 2 potential intracellular targets of NE (CCNE1 and CCNE2) on clinical outcome in a population of 205 primary breast cancer patients. By univariate analysis, CCNE1, CCNE2, estrogen receptor and grade significantly predicted relapse free interval (RFI). NE and PR3 did not achieve statistical significance. In a multivariate analysis, elevated CCNE2 [hazard ratio (HR) 2.10, p = 0.008] predicted shorter RFI. In subgroup analyses of the tamoxifen-only treated patients, high CCNE1 levels predicted treatment resistance, while high levels of CCNE2 were associated with poor RFI in untreated patients. Investigation of the relationship between CCNE1, CCNE2 and NE did not show any impact on RFI. To conclude, this study was the first to evaluate these markers at the mRNA level by RT-PCR in a series of primary breast cancer patients, and our results confirmed the impact of high CCNE levels on clinical outcome in systemically untreated and of CCNE1 in tamoxifen-only treated early breast cancer patients. © 2006 Wiley-Liss, Inc. [source] Phasing possibilities using different wavelengths with a xenon derivativeJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 2 2002Santosh Panjikar Xenon derivatives are generally expected to be isomorphous with the native; however, the K - and L -absorption edges are not easily accessible on most synchrotron beamlines, which might limit their usefulness in phase determination. Various phasing procedures for xenon-derivatized porcine pancreatic elastase have been investigated using data sets measured at three generally accessible wavelengths. The importance of highly redundant data in measuring precise anomalous differences is highlighted and it is shown that, after such measurements, a single isomorphous replacement anomalous scattering (SIRAS) procedure yields a better phase set than those generated by single anomalous scattering (SAS) or multiwavelength anomalous diffraction (MAD) procedures. [source] Specificities of proteases for use in leather manufactureJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 3 2006Farhad Foroughi Abstract Proteases are used in leather manufacture in the processes of soaking, unhairing and bating of hides and skins. However proteases can be relatively non-specific in their usage, and for improved efficacy of enzyme biocatalysis within the industry, an analysis of specific activities of enzymes towards skin proteins was undertaken. Most commercial proteases for soaking showed substantial activity against the substrates elastin,Congo Red and Azocoll but little or no activity against keratin,azure and hide powder black. Enzymes used for unhairing in conjunction with 30% of the usual concentration of sulfide to effect chemical unhairing showed moderate activity against all substrates tested (selected as representative of skin proteins), while proteases used in bating showed activity against Azocoll and elastin,Congo Red but had no keratinase activity and little activity against hide powder black. Bating proteases and soaking proteases displayed similar activities at pH 8. Microbes isolated in the screening of organisms from putrefied skins included one fungal and two bacterial isolates whose extracellular enzymes had efficient unhairing activity without the addition of sulfide. Enzyme activities for these proteases included high activity measured against Azocoll with little or no activity against elastin,Congo Red, keratin,azure and hide powder black. Neither elastase nor keratinase activities were determined as being essential for unhairing. Copyright © 2005 Society of Chemical Industry [source] Elastin in oral connective tissue modulates the keratinization of overlying epitheliumJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2010Po-Chen Hsieh Hsieh P-C, Jin Y-T, Chang C-W, Huang C-C, Liao S-C, Yuan K. Elastin in oral connective tissue modulates the keratinization of overlying epithelium. J Clin Periodontol 2010; 37: 705-711 doi: 10.1111/j.1600-051X.2010.01542.x Abstract Aim: One of the most discernable differences between keratinized and non-keratinized oral mucosas is the quantity of elastin they contain in the connective tissues. Whether elastin modulates the keratin expression of oral epithelial cells is unknown. Methods: Four specimens containing both keratinized and non-keratinized mucosas were processed for immunohistochemical (IHC) stainings for elastin and four keratins. Six keratinized and non-keratinized portions of oral mucosas were dissected and cultured on an organ culture system. Purified elastin and elastase were added separately to the media. After 14 days, the mucosas were examined for four keratin expressions. Cell cultures of keratinized and non-keratinized gingival fibroblasts were established and tested for elastin expression. Oral mucosa equivalents were then engineered and tested for keratin expression. Results: Keratinized epithelium exclusively expressed keratin-1 and -10 (K1/10), while non-keratinized epithelium expressed keratin-4 and -13 (K4/13). Only non-keratinized fibroblasts expressed elastin in cell culture. Both the native and the engineered keratinized gingiva changed phenotypes and expressed K4/13 when treated with exogenous elastin. On the contrary, the native non-keratinized mucosa started to express K1/10 when elastase eradicated inherent elastin. Conclusions: Our study demonstrated that the elastin in the oral connective tissue is important for the non-keratinized phenotypes of overlaying epithelium. [source] Salivary interleukin-1, concentration and the presence of multiple pathogens in periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2009Ulvi Kahraman Gursoy Abstract Aim: This study aimed to find salivary enzymes and/or cytokines that would reflect periodontitis, alone or in combination with salivary microbial markers. Material and Methods: The salivary concentrations of elastase, lactate dehydrogenase, interleukin-1, (IL-1,), interleukin-6, and tumour necrosis factor- ,, and the presence of five periodontal pathogens, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Treponema denticola, were analysed from salivary specimens of 165 subjects, a subpopulation of Health 2000 Health Examination Survey in Finland; 84 of the subjects had probing pocket depth (PPD) of 4 mm at 14 or more teeth (the advanced periodontitis group), while 81 subjects had no teeth with PPD of 4 mm (the control group). All subjects had at least 20 teeth and no systemic diseases. Results: Among the salivary cytokines and enzymes tested, IL-1, was the only biomarker associated with periodontitis. An association was also found with the presence of multiple periodontal pathogens. Salivary IL-1, and the presence of multiple periodontal pathogens were associated with periodontitis at the same magnitude, when they were in the logistic regression model individually or together. Conclusion: We suggest that salivary IL-1, and the presence of multiple periodontal pathogens in saliva should be studied more thoroughly as markers of periodontitis. [source] PMN responses in chronic periodontal disease: evaluation by gingival crevicular fluid enzymes and elastase-alpha-1-proteinase inhibitor complexJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2002Rainer Buchmann Abstract Objectives: In the present trial, the hypothesis was examined that the local PMN responses in untreated and treated chronic periodontitis can be differentiated by gingival crevicular fluid lysosomal enzyme activities and elastase-alpha-1-proteinase inhibitor complex. Methods: In nine subjects (average age 49.2 ± 7.1 years) with chronic periodontitis, clinical parameters and markers of the PMN-derived inflammatory tissue response in gingival crevicular fluid (GCF) were assessed before and 6 months after surgical periodontal therapy. Myeloperoxidase (MPO), beta-N-acetyl-hexosaminidase (beta-NAH) and cathepsin D (CD) were analyzed as indicators of the PMN-associated host tissue destruction, and elastase-alpha-1-proteinase inhibitor complex (alpha-1-EPI) as the major serum protein inactivating PMN elastase. The total activities of the lysosomal enzymes MPO and beta-NAH were evaluated spectrophotometrically, the CD levels by liquid scintillation counting with [14C] hemoglobin as substrate, and the total alpha-1-proteinase inhibitor complex using a sandwich-immunoassay. Results: The clinical parameters revealed a statistical significant decrease at the 6-month reexamination. PD levels dropped from 5.40 to 2.88 mm (change 2.52 ± 1.04 mm), the CAL scores from 6.67 to 4.43 mm (change 2.24 ± 0.77 mm). The 30 s GCF volumes dropped from 129.8 to 68.6, displaying a change of 61.1 ± 18.6, p , 0.05. The decrease in total MPO, beta-NAH and CD levels (medians: 1.7/0.6 µU MPO, 0.035/0.020 µU beta-NAH, 1.3/0.5 ng CD) following therapy was associated with a significant drop in total GCF amounts of alpha-1-EPI from 76.3 ng at baseline to 52.4 ng after 6 months. Conclusion: The clinical healing in chronic periodontal disease is associated with a downregulation of the local PMN responses following periodontal therapy. The reorganization of periodontal tissues is characterized by a decrease of lysosomal enzyme activities and the alpha-1-proteinase inhibitor complex in gingival crevicular fluid. [source] Granulocyte elastase, matrix metalloproteinase-8 and prostaglandin E2 in gingival crevicular fluid in matched clinical sites in smokers and non-smokers with persistent periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 5 2002B. Söder Abstract Background/aims: Smokers with persistent periodontitis may have granulocytes with impaired function. This study aimed to determine the levels of granulocyte elastase, matrix metalloproteinase-8 (MMP-8) and prostaglandin E2 (PGE2) in gingival crevicular fluid (GCF) in smokers and non-smokers with persistent periodontitis. Methods: We analyzed GCF from 70 matched sites in 29 periodontitis and 6 gingivitis sites in 34 subjects, 17 smokers, and 17 non-smokers. We also analyzed separately GCF from 28 of these subjects, 14 smokers and 14 non-smokers in 14 matched periodontitis sites. The following measurements were made: elastase complexed to ,1 -antitrypsin (EA-,1AT) and MMP-8 with ELISA, functional elastase with a chromogenic substrate, and PGE2 with radioimmunoassay (125I RIA). The significance of the findings was determined with Mann-Whitney test. Results: In the 29 matched periodontitis sites, smokers had significantly more functional elastase (p<0.005) and more EA-,1AT (p<0.05) than non-smokers. In the 14 matched periodontitis sites in 14 smokers and 14 non-smokers, the former had significantly more functional elastase than the latter (p<0.001). A significant correlation was found between EA-,1AT and MMP-8 in smokers (p<0.05) and non-smokers (p<0.001) and a positive correlation between levels of functional elastase and MMP-8 in non-smokers (r2=0.98; p<0.001). Conclusions: Granulocyte function seems to be impaired in smokers with persistent periodontitis. The cells react to the bacterial challenge by releasing serine proteases, which reflect the degradation of connective tissue. The risk of progression of the disease is therefore higher in smokers with persistent periodontitis than in non-smokers. Zusammenfassung Hintergrund, Ziele: Raucher mit bestehender Parodontitis haben möglicherweise Granulozyten mit beeinträchtigter Funktion. Diese Studie zielt auf die Bestimmung der Levels von Granulozytenelastase, Matrix-Metalloproteinase-8 (MMP-8) und Prostaglandin E2 (PGE2) in der krevikulären gingivalen Flüssigkeit (GCF) bei Rauchern und Nichtrauchern mit bestehender Parodontitis. Methoden: Wir analysierten GCF von 70 entsprechenden Flächen bei 29 Parodontitis und 6 Gingivitisflächen von 34 Personen, 17 Rauchern und 17 Nichtrauchern. Wir analysierten zusätzlich getrennt die GCF von 28 dieser Personen: 14 Raucher und 14 Nichtraucher von 14 entsprechenden parodontalen Flächen. Die folgenden Messungen wurden vorgenommen: Elastasekomplex zu ,1 -Antitrypsin (EA-,1AT) und MMP-8 mit ELISA, funktionelle Elastase mit chromogenem Substrat und PGE2 mit Radioimmunoassay (125I RIA). Die Signifikanz der Ergebnisse wurde mit dem Mann-Whitney Test bestimmt. Ergebnisse: In den 29 entsprechenden parodontalen Flächen hatten die Raucher signifikant mehr funktionelle Elastase (p<0.005) und mehr EA-,1At (p<0.05) als Nichtraucher. Bei den 14 entsprechenden parodontalen Flächen der 14 Raucher und 14 Nichtraucher hatten die ersten signifikant mehr funktionelle Elastase als die letzteren (p<0.001). Eine signifikante Korrelation wurde zwischen EA-,1AT und MMP-8 bei Rauchern (p<0.05) und Nichtrauchern (p<0.001) gefunden und eine positive Korrelation zwischen den Levels der funktionellen Elastase und MMP-8 bei Nichtrauchern (r2=0.98; p<0.001) festgestellt. Schlussfolgerungen: Die Granulozytenfunktion scheint bei Rauchern mit bestehender Parodontitis beeinträchtigt zu sein. Die Zellen reagieren auf die bakterielle Herausforderung durch Freisetzung von Serinproteasen, die die Degradation von Bindegewebe reflektiert. Das Risiko einer Progression dieser Erkrankung ist deshalb bei Rauchern mit bestehender Parodontitis höher als bei Nichtrauchern. Résumé Origine, but: Les fumeurs avec parodontite persistante pourraient avoir des granulocytes ayant des fonctions déréglées. Cette étude a eu pour but de déterminer les niveaux d'élastase granulocytaire, de la métallo-protéinase-8 de la matrice (MMP-8) et de la prostaglandine E2 (PGE2) dans le fluide créviculaire gingival (GCF) chez les fumeurs et les non-fumeurs avec parodontite persistante. Méthodes: Le GCF a été prélevé de 70 sites équivalents dans 29 parodontites et 6 sites avec gingivite chez 34 sujets, 17 fumeurs et 17 non-fumeurs. Le GCF de 28 de ces sujets a été analysé séparément, 14 fumeurs et 14 non-fumeurs dans 14 sites équivalents du point de vue parodontite. Les mesures suivantes ont été relevées: l'élastase avec ,1 -antitrypsine (EA-,1AT) et MMP-8 par ELISA, l'élastase fonctionnelle avec un substrat chromogénique, et PGE2 avec un essai radio-immunitaire (125I RIA). La signification de ces découvertes a été par l'utilisation du test de Mann-Whitney. Résultats: Dans les 29 sites équivalents, les fumeurs avaient significativement plus d'élastase functionnelle (p<0.005) et plus de EA-,1AT (p<0.05) que les non-fumeurs. Dans les 14 sites équivalents du point de vue parodontite, les 14 fumeurs avaient significativement plus d'élastase fonctionnelle que les 14 non-fumeurs (p<0.001). Une relation significative a étéétablie entre EA-,1AT et MMP-8 chez les fumeurs (p<0.05) et les non-fumeurs (p<0.001) et une relation positive entre les niveaux d'élastase fonctionnelle et de MMP-8 chez les non-fumeurs (r2=0.98; p<0.001). Conclusions: La fonction granulocytaire semble être altérée chez les fumeurs avec parodontite persistante. Les cellules réagissent à l'attaque bactérienne en relâchant des protéases sérine, ce qui démontre une dégradation du tissu conjonctif. Le risque de progression de la maladie est ainsi plus élevé chez les fumeurs avec parodontite persistante que chez les non-fumeurs. [source] Inhibition of elastase activity by essential oils in vitroJOURNAL OF COSMETIC DERMATOLOGY, Issue 4 2002Masahiro Mori Summary, Background, Essential oils are widely used, for example in aromatherapy and aroma massage. In aroma massage, essential oil, diluted with vegetable oil, is rubbed onto the skin. Components of essential oil penetrate into the skin and have an influence on the dermis. Elastase is an enzyme which degenerates dermal elastin. Elastase activity is believed to contribute to cutaneous wrinkling and ageing. Aim, To investigate the inhibitory effect of essential oils on elastase activity. Methods, Inhibition of elastase activity by various essential oils was assessed using two elastase enzymes: porcine pancreatic elastase (PPE) and human neutrophil elastase (HNE). Results, Elastase activity was inhibited by various essential oils, especially by those oils derived from lemons, juniper and grapefruit. Although the specific inhibitory component was not determined, lemon oil had the greatest inhibitory effect on PPE. Some essential oils also inhibited HNE. Conclusions, These studies demonstrate a possible rationale for the use of essential oil massage as a preventive treatment for cutaneous wrinkling and ageing. [source] Pathogenic cysteine mutations affect progranulin function and production of mature granulinsJOURNAL OF NEUROCHEMISTRY, Issue 5 2010Jun Wang J. Neurochem. (2010) 112, 1305,1315. Abstract Frontotemporal dementia with ubiquitin-positive inclusions (FTLD-U) can be caused by mutations in the progranulin gene (GRN). Progranulin (PGRN) is a cysteine-rich growth factor, which is proteolytically cleaved by elastase to produce several granulins (GRNs). All FTLD-U mutations in GRN characterized to date result in reduced secreted PGRN protein. We recently reported a Spanish family with progressive non-fluent aphasia and dementia in which a novel C521Y mutation segregates with disease. A second cysteine mutation (C139R) has also been reported to be disease specific. Allele-specific mRNA expression assays in brain reveal that the C521Y mutant allele is expressed at similar levels to the wild-type allele. Furthermore, plasma PGRN levels in C521Y carriers are comparable with non-carrier family relatives, suggesting that the mutation does not affect PGRN protein expression and secretion in vivo. Despite normal PGRN levels C521Y and C139R mutant GRNs show reduced neurite growth-stimulating activity in vitro. Further study revealed that these mutations also cause impaired cleavage of PGRN by elastase. Our data suggest that these mutations affect the function of full-length PGRN as well as elastase cleavage of PGRN into GRNs, leading to neurodegeneration. [source] Outcome of pregnancy after laser conization: Implications for infection as a causal link with preterm birthJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2008Hitoshi Masamoto Abstract Objective:, To investigate a causal link between infection and preterm birth in women with a shortened cervix induced by prior laser conization. Methods:, We conducted a retrospective review of the outcomes of 47 singleton pregnancies with a history of laser conization. Cervical length was measured between 17 and 23 weeks of gestation. Receiver-operating characteristic curves were used to determine the best cut-off point for the cervical length for predicting spontaneous preterm birth. We measured infectious markers in 12 women who had experienced preterm labor. Results:, Nine women had had premature labors and three had had late abortions. The mean ± SD cervical length was 33.1 ± 9.1 mm. The optimal cut-off for predicting preterm delivery was 25 mm with a sensitivity and specificity of 75.0% and 97.1%, respectively. Concentrations of granulocyte elastase were positive in five of the six samples determined. The white blood cell count and C-reactive protein levels were elevated in four out of the six patients. Sixty-seven percent of the vaginal cultures were positive for bacteria. Chorioamnionitis was present in seven women. Conclusions:, For the prediction of preterm birth in patients with a history of conization, it is helpful to look for signs of local infection when the cervical length is less than 25 mm. [source] The defensive role of lysozyme in human gingiva in inflammatory periodontal diseaseJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2009R. Younes Background and Objective:, The presence of lysozyme in human gingiva has not previously been demonstrated. In this study, we looked for evidence for the potential role of lysozyme as a protector of gingival elastic fibres. The objective of this study was also to determine the ex vivo susceptibility to hydrolysis of gingival elastic fibres from patients with or without periodontal disease by human leukocyte elastase and by human cathepsin G. Materials and Methods:, Using gingival tissue sections from eight control, 10 gingivitis and 10 periodontitis patients, we evaluated the area fraction occupied by gingival elastic fibres (after selective staining) by the use of automated image analysis. In the ex vivo experiments, serial tissue sections from four control, four gingivitis, four young periodontitis and four aged periodontitis patients were submitted to the action of human leukocyte elastase and cathepsin G, after which enzymatic activities were determined by image analysis. Indirect immunodetection of lysozyme was also done on tissue sections for all patients included in this study. Results:, Large variations of the area fraction occupied by elastic fibres were observed in human gingiva from young and aged patients with and without periodontal disease. In control and gingivitis patients, leukocyte elastase and cathepsin G had high comparable elastin solubilizing activities. With young and aged periodontitis patients, the two serine proteinases had weak elastin solubilizing activities. Lysozyme appeared to be present at the periphery of gingival elastic fibres in periodontitis patients. Conclusion:, Lysozyme can be considered an important natural protector of elastic fibres in pathological gingiva. [source] Neutrophils in chronic and aggressive periodontitis in interaction with Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitansJOURNAL OF PERIODONTAL RESEARCH, Issue 3 2009A. Guentsch Background and Objective:, This study analyzed the interaction of Porphyromonas gingivalis ATCC 33277 and Aggregatibacter actinomycetemcomitans Y4 with peripheral blood polymorphonuclear neutrophils taken from patients with aggressive periodontitis and chronic periodontitis. Material and Methods:, Peripheral blood polymorphonuclear neutrophils obtained from 12 patients with chronic periodontitis, six patients with aggressive periodontitis and 12 healthy controls were exposed to P. gingivalis and A. actinomycetemcomitans following opsonization of the bacteria using the patient's own serum. Serum immunoglobulin G (IgG) levels against both periodontopathogens were measured. Phagocytosis and killing of the bacteria, as well as the extracellular human neutrophil elastase activity, were quantified. The total amount and the extracellular release of reactive oxygen species were measured using luminol-dependent and isoluminol-dependent chemiluminescence. Results:, Polymorphonuclear neutrophils from patients with chronic (62.16 ± 19.39%) and aggressive (43.26 ± 26.63%) periodontitis phagocytosed more P. gingivalis than the healthy controls (24.43 ± 19.87%) at the 30-min time point after exposure to the bacteria (p < 0.05). High serum IgG levels against P. gingivalis and A. actinomycetemcomitans were detected in subjects with periodontitis. Polymorphonuclear neutrophils from subjects with chronic and aggressive periodontitis released significantly more reactive oxygen species and demonstrated greater human neutrophil elastase activity in the absence of any stimulus than polymorphonuclear neutrophils from healthy controls (p < 0.05). Polymorphonuclear neutrophils in chronic periodontitis released significantly more reactive oxygen species when exposed to P. gingivalis and A. actinomycetemcomitans than polymorphonuclear neutrophils in aggressive periodontitis. Conclusion:, High serum IgG levels against P. gingivalis and A. actinomycetemcomitans promote phagocytosis in periodontitis. The extracellular release of reactive oxygen species and neutrophil elastase by polymorphonuclear neutrophils may also contribute to damage of the surrounding periodontal tissues. [source] Risk factors for periodontitis in HIV+ patientsJOURNAL OF PERIODONTAL RESEARCH, Issue 3 2004Tamer Alpagot Objective:, The purpose of this study was to identify risk factors for periodontitis associated with human immunodeficiency virus (HIV) infection. Methods:, A total of 152 HIV+ patients were recruited from the CARE clinic at the University of the Pacific School of Dentistry. Clinical measurements (gingival index, plaque index, bleeding index, probing depth, and attachment loss), gingival crevicular fluid (GCF) and subgingival plaque samples were taken from eight sites of each patient at baseline and 6-month visits. GCF neutrophil elastase was determined by measurement of p -nitroanalide resulting from hydrolysis of an elastase-specific peptide. GCF ,-glucuronidase was determined by release of 4-methylumbelliferone from hydrolysis of a specific substrate. A bacterial concentration fluorescence immunoassay was used to detect periodontopathic bacteria in subgingival plaque samples. Results:, Viral load, age, smoking pack-years, Fusobacterium nucleatum, Prevotella intermedia, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, neutrophil elastase, and ,-glucuronidase were significantly correlated with clinical measurements (0.0001 < p < 0.05). Significantly higher levels of elastase, ,-glucuronidase, F. nucleatum, P. intermedia, and A. actinomycetemcomitans were found at progressing sites than in non-progressing sites (0.001 < p < 0.05). Conclusions:, These data indicate that age, smoking pack-years, viral load, F. nucleatum, P. intermedia, A. actinomycetemcomitans, elastase, and ,-glucuronidase are risk factors for periodontitis in HIV+ patients. [source] Effects of hyperoncotic or hypertonic,hyperoncotic solutions on polymorphonuclear neutrophil count, elastase- and superoxide-anion production: a randomized controlled clinical trial in patients undergoing elective coronary artery bypass graftingACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2007G. P. Molter Background:, Hypertonic,hyperoncotic solutions may be an effective treatment for systemic inflammatory response syndrome (SIRS). With regard to the immunomodulatory effects of these drugs, previous studies demonstrated controversial results. Therefore, the present study investigated the influence of different hyperoncotic and hypertonic,hyperoncotic solutions on polymorphonuclear neutrophil leukocyte (PMNL) count, elastase and superoxide-anion production in patients undergoing elective coronary artery bypass grafting (CABG) with cardiopulmonary bypass. Methods:, Fifty patients scheduled for elective CABG with cardiopulmonary bypass were randomly assigned to five groups: (i) NaCl 0.9%, 750 ml/m2 body surface area (BSA); (ii) hydroxyethylic starch 10%, 250 ml/m2 BSA and NaCl 0.9%, 400 ml/m2 BSA; (iii) dextran 10%, 250 ml/m2 BSA and NaCl 0.9%, 300 ml/m2 BSA; (iv) hypertonic sodium chloride 7.2%/hyperoncotic hydroxyethylic starch 10%, 150 ml/m2 BSA; and (v) hypertonic sodium chloride 7.2%/hyperoncotic dextran 10%, 150 ml/m2 BSA. Blood samples were drawn from arterial, central venous and coronary artery sinus catheters peri-operatively. PMNL count, superoxide-anion production and elastase were recorded. Results:, PMNL counts and elastase activity increased in all groups after reperfusion. Superoxide-anion production showed only minor changes. Between groups, no significant differences were demonstrated. Conclusions:, Infusion of clinically relevant doses of hypertonic,hyperoncotic solution did not affect PMNL count, elastase- or superoxide-anion production during elective CABG with cardiopulmonary bypass. [source] Therapeutic potential of sulfamides as enzyme inhibitorsMEDICINAL RESEARCH REVIEWS, Issue 6 2006Jean-Yves Winum Abstract Sulfamide, a quite simple molecule incorporating the sulfonamide functionality, widely used by medicinal chemists for the design of a host of biologically active derivatives with pharmacological applications, may give rise to at least five types of derivatives, by substituting one to four hydrogen atoms present in it, which show specific biological activities. Recently, some of these compounds started to be exploited for the design of many types of therapeutic agents. Among the enzymes for which sulfamide-based inhibitors were designed, are the carbonic anhydrases (CAs), a large number of proteases belonging to the aspartic protease (HIV-1 protease, ,-secretase), serine protease (elastase, chymase, tryptase, and thrombin among others), and metalloprotease (carboxypeptidase A (CPA) and matrix metalloproteinases (MMP)) families. Some steroid sulfatase (STS) and protein tyrosine phosphatase inhibitors belonging to the sulfamide class of derivatives have also been reported. In all these compounds, many of which show low nanomolar affinity for the target enzymes for which they have been designed, the free or substituted sulfamide moiety plays important roles for the binding of the inhibitor to the active site cavity, either by directly coordinating to a metal ion found in some metalloenzymes (CAs, CPA, STS), usually by means of one of the nitrogen atoms present in the sulfamide motif, or as in the case of the cyclic sulfamides acting as HIV protease inhibitors, interacting with the catalytically critical aspartic acid residues of the active site by means of an oxygen atom belonging to the HNSO2NH motif, which substitutes a catalytically essential water molecule. In other cases, the sulfamide moiety is important for inducing desired physico-chemical properties to the drug-like compounds incorporating it, such as enhanced water solubility, better bioavailability, etc., because of the intrinsic properties of this highly polarized moiety when attached to an organic scaffold. This interesting motif is thus of great value for the design of pharmacological agents with a lot of applications. © 2006 Wiley Periodicals, Inc. Med Res Rev [source] Topical glucocorticoids downregulate COX-1 positive cells in nasal polypsALLERGY, Issue 1 2009F. A. Ebbens Background: Influx of inflammatory cells is one of the hallmarks of nasal polyposis. As glucocorticoids (GC) are known to exhibit strong anti-inflammatory effects, these drugs are frequently used in the treatment of the disease. Part of the anti-inflammatory effects of GC is attributed to their interference with prostanoid synthesis. As cyclooxygenases (COX) are key enzymes in the synthesis of both pro- (COX-1, COX-2) and anti-inflammatory prostanoids (COX-2), we investigated the role of topical GC on COX-1, COX-2 and inflammatory markers in nasal polyps (NP). Methods: Immunohistochemical analysis of inflammatory markers (CD68, CD117, MBP, elastase, IgE, BB-1, IL-4, IL-5 and IL-6), COX-1 and COX-2 was performed on normal nasal mucosa (NM) (n = 18), non-GC treated NP (n = 27) and topical GC treated NP (n = 12). NP groups were matched for allergy, asthma and ASA intolerance. Results: Increased numbers of eosinophils, IL-5+ cells and IgE+ cells and decreased numbers of mastcells are striking features of NP inflammation (P < 0.05). In addition, increased numbers of COX-1+ cells are observed in NP epithelium compared to NM (P < 0.05). Conclusion: Topical GC significantly reduce the number of COX-1+ NP cells (P < 0.05), but have no significant effect on COX-2+ NP cells. No significant reduction in the number of eosinophils is observed for GC treated NP. The number of IL-5+ cells is however increased significantly upon GC treatment (P < 0.05). [source] | ||||||||||||||||||||||||||||||||||||||||