Nonoxynol-9 (N-9), a surfactant microbicide, has been shown to damage vaginal epithelium and increase the risk of HIV infection. Little is known about its effect on the immune function of the upper reproductive tract. The purpose of this study is to determine the effect of N-9 on endometrial expression of secretory leukocyte protease inhibitor (SLPI), a naturally occurring protein with antimicrobial activity, in-vivo and in-vitro. Tissue from endometrial biopsies was examined both before and after vaginal administration of N-9. Tissue explants from pre-treatment endometrial biopsies were also used as experimental models. The explants were incubated with three dosages of N-9 for 6 or 24 hours. All biopsy specimens of endometrial tissue and explants were immunohistochemically stained for SLPI. In-vivo there was no statistically significant difference between pre- and post-N-9 SLPI expression in the endometrium. The expression of SLPI was decreased by exposure to N-9 in explants in a dose-dependent ...

Inhaled recombinant secretory leukocyte protease inhibitor (rSLPI) has shown potential for the treatment of inflammatory lung conditions. Rapid inactivation of rSLPI by cathepsin L (Cat L) and rapid c

TY - JOUR. T1 - Secretory leukoprotease inhibitor inhibits cell growth through apoptotic pathway on ovarian cancer. AU - Nakamura, Keiichiro. AU - Takamoto, Norio. AU - Hongo, Atsushi. AU - Kodama, Junichi. AU - Abrzua, Fernando. AU - Nasu, Yasutomo. AU - Kumon, Hiromi. AU - Hiramatsu, Yuji. PY - 2008/5. Y1 - 2008/5. N2 - In light of the poor prognosis for ovarian cancer, research continues for innovative and efficacious treatment modalities. It is now widely accepted that new approaches for the treatment of ovarian cancers are pivotal in further improving prognosis of this disease. Secretory leukoprotease inhibitor (SLPI) is an 11.7-kDa non-glycosylated, serine protease inhibitor that has a broad inhibitory spectrum against serine protease. SLPI showed potential therapeutic inhibitory effects mediated by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), TNF-α, death receptor (DR)-4, DR-5 and TNF receptor (TNFR)-I expression which lead to an activation of apoptosis pathway ...

Background: SLPI (secretory leucocyte protease inhibitor) is a potent inhibitor of serine proteases with important functions in immunity and healing processes. SLPI knockout mice display impaired wound healing with increased inflammation, transforming growth factor β, and matrix metalloproteinase activity. In fact, SLPI is one of the first identified factors promoting healing so far. Since healing defects can contribute to left ventricular remodeling after myocardial infarction and to the development of heart failure, we determined the expression and function of SLPI in the heart.. Methods and results. In vitro SLPI expression was readily detected in neonatal rat ventricular myocytes by western and northern blots as well as immunohistochemistry. Survival after hydrogen peroxide challenge was significantly enhanced after pretreatment with SLPI. In parallel, SLPI significantly reduced oxidative stress, and increased glutathione content. In vivo, mice with targeted deletion of SLPI had decreased ...

Idiopathic pulmonary fibrosis is a progressive, fatal disease with limited treatment options. Protease-mediated transforming growth factor-β (TGF-β) activation has been proposed as a pathogenic mechanism of lung fibrosis. Protease activity in the lung is tightly regulated by protease inhibitors, particularly secretory leukocyte protease inhibitor (SLPI). The bleomycin model of lung fibrosis was used to determine the effect of increased protease activity in the lungs of Slpi− / − mice following injury. Slpi− / −, and wild-type, mice received oropharyngeal administration of bleomycin (30 IU) and the development of pulmonary fibrosis was assessed. Pro and active forms of matrix metalloproteinase (MMP)-2 and MMP-9 were measured. Lung fibrosis was determined by collagen subtype-specific gene expression, hydroxyproline concentration, and histological assessment. Alveolar TGF-β activation was measured using bronchoalveolar lavage cell pSmad2 levels and global TGF-β activity was assessed by ...

In the present study, we investigated the ability of microparticles isolated from synovial fluids from patients with rheumatoid arthritis or osteoarthritis to induce the synthesis and release of key cytokines of B-lymphocyte modulation such as B cell-activating factor, thymic stroma lymphopoietin, and secretory leukocyte protease inhibitor by rheumatoid fibroblast-like synoviocytes. Microparticles were analyzed in synovial fluids from patients with rheumatoid arthritis, osteoarthritis, microcristalline arthritis, and reactive arthritis. In addition, microparticle release after activation from various cell lines (CEM lymphocyte and THP-1 cells) was assessed. Microparticles were isolated by differential centrifugation, and quantitative determinations were carried out by prothrombinase assay after capture on immobilized annexin V. B cell-activating factor, thymic stroma lymphopoietin, and secretory leukocyte protease inhibitor release was evaluated by enzyme-linked immunosorbent assay. Microparticles

PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.

Although still in its infancy compared with pharmacological methods of drug delivery, gene therapy might be advantageous, owing to its less transient nature. Because of its natural tropism for the lung, adenovirus could be the vector of choice for gene therapy applications. Historically, most of these applications have been directed in the lung at chronic pathologies such as cystic fibrosis or cancer. This is by no means the best case, given the chronic nature of these pathologies in which a repeated administration of vectors would be necessary to achieve adequate levels of therapeutic transgenes. Unfortunately, the immune response directed against the currently available `first and second generation adenovirus vectors currently precludes their use in such settings. However, the generation of `gutless vectors (which express almost no viral genes) has shown to drastically improve the duration of transgene expression in rodent models [26]. This type of vector is an important feature of ...

Secretory leukoprotease inhibitor (SLPI) protects tissue against the destructive action of neutrophil elastase at the site of inflammation. Recent studies on new functions of SLPI have demonstrated that SLPI may play a larger role in innate immunity than merely as a protease inhibitor. To clarify the functions of SLPI in bacterial infections, we generated SLPI-deficient mice (SLPI−/− mice) and analyzed their response to experimental endotoxin shock induced by lipopolysaccharide (LPS). SLPI−/− mice showed a higher mortality from endotoxin shock than did wild type mice. This may be explained in part by our observation that SLPI−/− macro-phages show higher interleukin 6 and high-mobility group (HMG)-1 production and nuclear factor κB activities after LPS treatment than do SLPI+/+ macrophages. SLPI also affects B cell function. SLPI−/− B cells show more proliferation and IgM production after LPS treatment than SLPI+/+ B cells. Our results suggest that SLPI attenuates excessive ...

Antileukoproteinase, also known as secretory leukocyte protease inhibitor (SLPI), is an enzyme that in humans is encoded by the SLPI gene. SLPI is a highly cationic single-chain protein with eight intramolecular disulfide bonds. It is found in large quantities in bronchial, cervical, and nasal mucosa, saliva, and seminal fluids. SLPI inhibits human leukocyte elastase, human cathepsin G, human trypsin, neutrophil elastase, and mast cell chymase. X-ray crystallography has shown that SLPI has two homologous domains of 53 and 54 amino acids, one of which exhibits anti-protease activity (C-terminal domain). The other domain (N-terminal domain) is not known to have any function. This gene encodes a secreted inhibitor which protects epithelial tissues from serine proteases. It is found in various secretions including seminal plasma, cervical mucus, and bronchial secretions, and has affinity for trypsin, leukocyte elastase, and cathepsin G. Its inhibitory effect contributes to the immune response by ...

The human secretory leukocyte protease inhibitor (SLPI) is an 11.7 kD cysteine-rich protein that has been shown to possess anti-protease, anti-inflammatory, and antimicrobial properties. By using a Pichia pastoris strain that overproduces protein disulfide isomerase (PDI), we obtained greater than fivefold higher levels of SLPI than in strains expressing normal levels of PDI and containing multiple copies of the SLPI gene. Elevated levels of PDI also enhanced the specific activity of the secreted SLPI by helping it achieve a proper tertiary structure. Mass spectrometry analysis indicated a greater number of disulfide bonds in the SLPI produced by the PDI overexpression strain compared to the SLPI produced in strains with normal PDI levels. Although others have utilized a similar strategy to increase yield, we believe that this is the first example of PDI overexpression being demonstrated to enhance the folding and thus increase the biological activity of a protein produced in the yeast P. pastoris.

Clifford C. Taggart, Sally-Ann Cryan, Sinead Weldon, Aileen Gibbons, Catherine M. Greene, Emer Kelly, Teck Boon Low, Shane J. ONeill, Noel G. McElvaney ...

Secretory Leukocyte Peptidase Inhibitor (SLPI) functionality in health and disease: Secretory Leukocyte Peptidase Inhibitor (SLPI) is a serine protease inhibitor of cathepsin G, trypsin and chymotrypsin, but primarily against neutrophil elastase. Its major function is to inhibit inflammation by blocking the proteolytic activity of these proteinases released by leukocytes and also through down-modulation of several cytokines. The anti-inflammatory activity is also mediated by inhibition of the activation of the transcription nuclear factor NF-kB. Some studies localized the molecule within the cytosol and in secondary granules of neutrophils. Because of this, it is believed that neutrophil-derived SLPI may regulate the protease/antiprotease balance at sites of tissue inflammation. In relation with the adaptive immune system, it was suggested that SLPI modulates the cellular and humoral immune response, by decreasing the T cell proliferation and reducing the class switching. Also, it is known that ...

Background: Community-acquired pneumonia (CAP) is a common and potentially life-threatening infection. Innate immunity is the first line of defence, and antimicrobial peptides (AMPs) produced by white blood cells and at epithelial barriers participate by killing microorganisms and neutralizing bacterial toxins. We wanted to investigate whether concentrations of AMPs (1) are increased in CAP, (2) predict the clinical outcome, and (3) differ depending on the causative microbe. Methods: Plasma concentrations of AMPs were measured using an enzyme-linked immunosorbent assay in 89 patients with CAP, 21 patients with non-respiratory tract infections (non-RTI), and 63 healthy control subjects. Results: In subjects with CAP, mean plasma concentrations of secretory leukocyte protease inhibitor (SLPI) and bactericidal/permeability-increasing protein (BPI) were significantly higher than in healthy control subjects (85 vs 45 ng/ml, p , 0.001 and 48 vs 10 ng/ml, p , 0.001, respectively), but less markedly ...

(2000) Tseng, Tseng. FEBS Letters. Previous studies have suggested that human salivary secretory leukocyte protease inhibitor (SLPI) inhibits HIV-1 by binding to a host cell surface protein of unknown identity. Using the yeast two-hybrid assay, we identified a gene sequence encoding a novel SLPI-...

Background We conducted an exploratory study of genome-wide gene expression in whole blood and found that the expression of neutrophil elastase inhibitor (PI3, elafin) was down-regulated during the early phase of ARDS. Further analyses of plasma PI3 levels revealed a rapid decrease during early ARDS development. PI3 and secretory leukocyte proteinase inhibitor (SLPI) are important low-molecular-weight proteinase inhibitors produced locally at neutrophil infiltration site in the lung. In this study, we tested the hypothesis that an imbalance between neutrophil elastase (HNE) and its inhibitors in blood is related to the development of ARDS. Methodology/Principal Findings PI3, SLPI, and HNE were measured in plasma samples collected from 148 ARDS patients and 63 critical ill patients at risk for ARDS (controls). Compared with the controls, the ARDS patients had higher HNE, but lower PI3, at the onset of ARDS, resulting in increased HNE/PI3 ratio (mean = 14.5; 95% CI, 10.9-19.4, P|0.0001), whereas plasma

(1997) Vogelmeier et al. European Respiratory Journal. Secretory leukoprotease inhibitor (SLPI) and α 1-protease inhibitor α 1-PI) are powerful antiproteases currently under investigation for their potential to protect the lung from neutrophil elastase (NE). The aim of this study was to determine...

In view of the limited success of available treatment modalities for metastatic breast cancer, alternative and complementary strategies need to be developed. Adenoviral vector mediated strategies for breast cancer gene therapy and virotherapy are a promising novel therapeutic platform for the treatment of breast cancer. However, the promiscuous tropism of adenoviruses (Ads) is a major concern. Employing tissue specific promoters (TSPs) to restrict transgene expression or viral replication is an effective way to increase specificity towards tumor tissues and to reduce adverse effects in non-target tissues such as the liver. In this regard, candidate breast cancer TSPs include promoters of the genes for the epithelial glycoprotein 2 (EGP-2), cyclooxygenase-2 (Cox-2), α-chemokine SDF-1 receptor (stromal-cell-derived factor, CXCR4), secretory leukoprotease inhibitor (SLPI) and survivin. We employed E1-deleted Ads that express the reporter gene luciferase under the control of the promoters of interest. We

ALI is associated with a high mortality rate of up to 40%. There is an urgent need to develop effective therapeutics for the treatment of this condition.28 The biological properties of elafin have been well described since its discovery, highlighting elafin as a potential therapeutic for the treatment of inflammatory lung conditions.11 ,13 ,29 ,30 Due to the multi-factorial nature of ALI, which involves a complex network of pro-inflammatory cytokines and protease activities, protective host defence proteins such as elafin may be left vulnerable to enzymatic cleavage and inactivation. In keeping with previous reports, we showed elafin and SLPI levels to be significantly increased in patients with ALI compared with healthy volunteers.31 To ensure that this increase in antiprotease levels observed at the onset of ALI was not induced by mechanical ventilation, we measured elafin and SLPI levels in BALF from intensive care unit patients who were mechanically ventilated but did not fulfil criteria for ...

TY - JOUR. T1 - Regulatory effects of endogenous protease inhibitors in acute lung inflammatory injury. AU - Gipson, Teletha S.. AU - Bless, Nicolas M.. AU - Shanley, Thomas P.. AU - Crouch, Larry D.. AU - Bleavins, Michael R.. AU - Younkin, Ellen M.. AU - Sarma, Vidya. AU - Gibbs, Douglas F.. AU - Tefera, Wongelawit. AU - McConnell, Patrick C.. AU - Mueller, William T.. AU - Johnson, Kent J.. AU - Ward, Peter A.. PY - 1999/3/15. Y1 - 1999/3/15. N2 - Inflammatory lung injury is probably regulated by the balance between proteases and protease inhibitors together with oxidants and antioxidants, and proinflammatory and anti-inflammatory cytokines. Rat tissue inhibitor of metalloprotease-2 (TIMP-2) and secreted leukoprotease inhibitor (SLPI) were cloned, expressed, and shown to be up-regulated at the levels of mRNA and protein during lung inflammation in rats induced by deposition of IgG immune complexes. Using immunoaffinity techniques, endogenous TIMP-2 in the inflamed lung was shown to exist as a ...

P5 six rat DRG neurons were diluted to 35,000 cells ml in SATO media and handled with one mM dbcAMP, ten ug ml SLPI, or perhaps a volume of beads containing ten ug ml of SLPI protein. Cells were plated on CHO cell monolayers and incubated for 15 hours at 37 C. Neurons have been immunostained for BIII tubulin and neurite outgrowth was quantified as described above. siRNA experiments Accell SMARTpool rat Sunitinib price Smad2 siRNA, Accell Green Non Focusing on siRNA, and Accell Non Focusing on siRNA had been reconstituted to 100 uM working with one siRNA buffer. To assess transfection efficiency, P6 CGN and P1 rat cortical neurons have been prepared as described previously and diluted in supplemented Neurobasal A media. Neurons have been plated in poly L lysine coated 8 very well chamber slides at a density of 75,000 cells nicely. 24 hours later, the culture media in every properly was replaced with a hundred ul of 1 uM Accell Green Non Targeting siRNA in Accell siRNA delivery media. The neurons ...

TY - CHAP. T1 - Defensins and other antimicrobial peptides and proteins. AU - Lehrer, Robert I.. AU - Bevins, Charles L. AU - Ganz, Tomas. PY - 2005. Y1 - 2005. N2 - Endogenous antimicrobial peptides are widely distributed among vertebrates. Most are amphiphilic, polycationic molecules with an α-helical, cystine-stabilized β-sheet, or proline-rich structure. Secreted and cell-associated antimicrobial peptides enable their hosts to resist incursions by potential pathogens. Such peptides present a series of barriers to the pathogens, to evade or overcome. In humans (and other mammals), defensins and cathelicidins are the principal antimicrobial peptides of neutrophils and epithelial cells. Many mucosal surfaces are bathed by antimicrobial proteins, including lysozyme, lactoferrin, secretory leukoprotease inhibitor (SLPI), and secretory phospholipase A2. All defensins have largely β-sheet structure and contain three intramolecular cystine disulfide bonds. The smallest, .-defensins, are circular ...

Human neutrophil elastase (HNE) is a key mediator of tissue remodeling and inflammation. An excess of HNE activity has been implicated in the pathogenesis of inflammatory pulmonary diseases, e.g. bronchiectasis (BE), COPD, and pulmonary hypertension. HNE inhibitors could potentially restore the protease/anti-protease balance in these diseases providing a new therapeutic target.. BAY 85-8501 is a novel, selective and reversible HNE inhibitor with activity in the picomolar concentration range, which reveals target inhibition in the lung and ameliorates pulmonary inflammation in preclinical models.. This First-in-Man study evaluated BAY 85-8501 in a Single-Dose-Escalation (SDE) design with 0.05, 0.1, 0.2, 0.5 or 1.0 mg as oral liquid formulation in 37 healthy male subjects (27 active, 10 placebo).. The single dose treatments were safe and well tolerated without serious or severe adverse events and without any hints for mode of action or drug substance related adverse effects. All clinical safety ...

Overview. Inflammatory bowel (IBD) is a chronic gastrointestinal tract disorder of unknown cause and ill-defined pathogenesis. Interactions between the mucosal immune system, host genetic susceptibility, and environmental factors (e.g., normal microflora) have been implicated as causing intestinal inflammation. Two general hypotheses have been proposed: 1) inflammation is due to an abnormal immune response (e.g., host hypersensitivity caused by increased intestinal permeability, defective suppressor function of GALT, and/or other primary immunologic events) and, 2) inflammation is initiated by an appropriate immune response to a normal luminal constituent (dietary antigen or resident enteric flora). With either paradigm, both cellular components (activated intestinal B and T lymphocytes) and molecular elements (complement, prostanoids, leukotrienes, proinflammatory cytokines, leukocyte proteases, nitric oxide, and reactive oxygen species) likely contribute to mucosal inflammation. Clinical signs ...

1. The literature on conditions affecting the activity of proteolytic enzymes has been reviewed.. 2. Experimental data on the control of the activity of trypsin, leucoprotease, papain, serum antiprotease, leucopeptidase, and pancreatic peptidase have been presented. These data indicate that:. (a) The polymorphonuclearleucocytes of the cat contain abundant proteinase and peptidase active at neutral pH; those of the rabbit lack proteinase active at neutral pH.. (b) Reducing agents, including several biologically important thiol-sulfhydryl compounds and ascorbic acid, inhibit the activity of leucoprotease and trypsin. For each reductant the degree of inhibition is proportional to the reducing capacity of the medium.. (c) p-Aminobenzoic acid, sulfonamides (especially sulfathiazole), and many diphenyl sulfones inhibit the activity of leucoprotease.. (d) Serum, plasma, several heavy metals, ammonium salts, asparagine, thiourea, heparin, glutamic acid, tyrothricin, calcium chloride, and bile salts and ...

Sigma-Aldrich offers abstracts and full-text articles by [Shashi Chillappagari, Jenni Preuss, Sebastian Licht, Christian Müller, Poornima Mahavadi, Gaurav Sarode, Claus Vogelmeier, Andreas Guenther, Lutz Nahrlich, Bruce K Rubin, Markus O Henke].

A protease/anti-protease imbalance is a characteristic feature of inflammatory lung diseases such as cystic fibrosis (CF) and COPD. However, alpha-1-antitrypsin (AAT) enzyme replace- ment therapy (ERT) trials have not shown conclusive evidence of therapeutic benefit. Here, we assessed whether transduction of murine lungs with a pseudotyped SIV vector, rSIV.F/HN-hCEF-AAT, generates therapeutic levels of AAT. Mice were transduced with rSIV.F/HN-hCEF-AAT (1.4e8 TU/mouse) by nasal instillation and culled 10 days post-trans- duction. AAT levels in lung homogenate and epithelial lining fluid (ELF) were 3 logs above controls (p | 0.05), and hAAT concentration in ELF was 92-28lg/ml, similar to the thera- peutic AAT level in ELF of 70lg/ml. For comparison trans- fection of mouse lung with cationic lipid GL67A complexed to hCEFI-AAT only led to 0.4-0.1lg/ml AAT in ELF. A neutrophil elastase (NE) activity assay showed that the recombinant AAT successfully neutralised NE activity (p | 0.05). In a separate

Lung disease. Rationale: Alpha-1-antitrypsin (AAT) is the major serum anti-protease protein in humans. Its genetic deficiency (AATD) led in 1985 to the protease-antiprotease imbalance hypothesis to explain emphysema development. This hypothesis predicted that restoring the balance by intravenous AAT, isolated from healthy blood donors, would stop the progression of emphysema. To date, this has not been proven by an effect on lung function values (FEV1 or DLCO) in clinical trials. Therefore, we aim to investigate a new hypothesis. Based on our preliminary results we hypothesized that altered PBMC subpopulations and a consequent defect in the CX3CL1/CX3CR1 axis has a critical role in the pathogenesis of emphysema associated with inherited AAT deficiency. Furthermore, altered subsets of PBMC, like patrolling monocytes, may contribute to pulmonary microvascular endothelial cell (pMVEC) damage, which is enhanced in emphysema.. Objective: Primary: to identify in the study population the variability in ...

The Sign Language Proficiency Interview (SLPI:ASL) involves a one-to-one conversation in sign language between an interviewer and candidate/interviewee. Interview content varies according to the background, job responsibilities, schooling, and other interests of each SLPI:ASL candidate/interviewee.. The SLPI:ASL was adapted by Bill Newell and Frank Caccamise from the Language/Oral Proficiency Interview (L/OPI), an interview technique for assessing spoken language communication skills. Just as the L/OPI may be used to assess a variety of spoken languages the SLPI:ASL may be used to assess a variety of sign languages. For example, it is used in Kenya as SLPI:KSL, in South Africa as SLPI:SASL, and in New Zealand as SLPI:NZSL.. SLPI:ASL interviews are recorded and subsequently rated independently by SLPI:ASL raters. The basis for ratings is the SLPI:ASL Rating Scale, a standard scale based on the sign language communication skills of highly skilled, knowledgeable native/native-like signers. In ...

Antiprotease targeting : altered specificity of α1-antitrypsin by amino acid replacement at the reactive centre Academic Article ...

[116 Pages Report] Check for Discount on United States Protease Inhibitor Market Report 2016 report by QYResearch Group. Notes: Sales, means the sales volume of Protease Inhibitor Revenue,...

The ACL is one of four important ligaments that stabilise the knee joint. In a healthy knee, it is especially important in providing stability during pivoting or rotatory movements. If the ACL has been ruptured or torn, it can be reconstructed by replacing the ligament with a graft. This will prevent the knee from giving way. Reconstruction remains gold standard for the treatment of ACL injuries ...

Cervical Mucus Before Period fertile, wet, watery It will be there around five days about before your period that you will notice the biggest of changes in your cervical mucus, and this is the time when you will produce the most.

Cervical mucus can give you a lot of information about your fertility phase. In fact, every small change in the cervical mucus has its own significance. To know more regarding the same, keep reading.

Cervical mucus can give you a lot of information about your fertility phase. In fact, every small change in the cervical mucus has its own significance. To know more regarding the same, keep reading.

Cervical mucus testing is important for getting pregnant. Why? Volume and texture of your cervical mucus let you know if youre ovulating normally.

Cervical mucus is a substance secreted by the glands of a womans cervix. It serves as an aid for conception and helps protect the...

Spycam installed in asian public toilet caught teen peeing with thick cervical mucus dripping from her cunt. She also cleans pussy discharge on dirty panties

If youre trying to conceive, understanding the stages of cervical mucus can significantly aid your quest of conception. Heres everything you need to know.

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