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Inherited Differences in Alpha1-Antitrypsin
Published in Stephen D. Litwin, Genetic Determinants of Pulmonary Disease, 2020
Antiproteolytic activity in mammalian sera is not a new observation; it was first observed by investigators during the last century [4,5]. Advances in protein chemistry have revealed that this activity is due to a group of individual inhibitors. Human serum alone contains seven distinct major protease inhibitors (Table 1) which differ in their specificity range. For example, alpha2macroglobulin shows a broad spectrum of inhibition which includes proteases with different mechanisms of action such as trypsin and papain [6]. Alpha1antichymotrypsin neutralizes only chymotrypsin and chymotrypsin-like enzymes; it does not inhibit trypsin. The recently described anti-collagenase is apparently quite specific [7]. Other enzymes have not been extensively tested. The major inhibitors present in human sera are listed in Table 1.
Collagen Diseases and Intrauterine Growth Retardation
Published in Asim Kurjak, John M. Beazley, Fetal Growth Retardation: Diagnosis and Treatment, 2020
Danniel Weinstein, Joseph G. Schenker
In rheumatoid arthritis the serum and fluid of most patients contain heterogeneous antibodies (rheumatoid factor). Unknown etiological factors set into motion the immunological events that lead to the appearance and the continued production of rheumatoid factor in the pathogenesis of RA. Immunological mechanisms play an important role in the development of synovitis. Antinuclear antibodies, DNA, and breakdown products of complement appear in the synovial fluid with activation of the component cascade which releases inflammatory peptides, causing migration of the inflammatory cells. The release of collagenases causes local damage.92
Functional Study of Lysosomal Nutrient Transporters
Published in Bruno Gasnier, Michael X. Zhu, Ion and Molecule Transport in Lysosomes, 2020
Xavier Leray, Corinne Sagné, Bruno Gasnier
Two buffers are used: Modified Barth’s solution (MBS): 88 mM NaCl, 1 mM KCl, 2.4 mM NaHCO3, 0.82 mM MgSO4, 0.33 mM Ca(NO3)2, 0.41 mM CaCl2, 5 mM Hepes pH 7.4. This solution is used to maintain oocytes.Ca2+-free oocyte Ringer solution (OR2-): 82.5 mM NaCl, 2.5 mM KCl, 1 mM MgCl2, 5 mM Hepes pH 7.4. This solution is used for collagenase treatment. The absence of Ca2+ is critical to preserve oocyte integrity during defolliculation because purified collagenase preparations often contain contaminating proteases activated by Ca2+.
Generation of a novel ex-vivo model to study re-endothelialization
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2023
Siti Sarah Azman, Muhammad Dain Yazid, Nur Azurah Abdul Ghani, Raja Zahratul Azma Raja Sabudin, Mohd Ramzisham Abdul Rahman, Nadiah Sulaiman
In this study, various parameters were tested to optimiza a successful gentle denudation protocol that: (1) retain vessel’s integrity, (2) successful removal of EC layer, and (3) preservation of GAG near lumen area. Maintaining vessel integrity is crucial to establish a viable model for subsequent re-endothelialization studies. Previous work by Kural, et al. also demonstrated that enzymatic denudation resulted in lower percentage of SMC death and proliferation compare to mechanical denudation [18]. In our study, denudation with trypsin-EDTA enzyme showed significant endothelial denudation compared to trypLE Select. This is due to the mechanism of trypsin, a proteolytic enzyme that breaks down protein anchoring EC to the underlying extracellular matrix (ECM) and EDTA, which chelates calcium ions that are crucial in maintaining cell-cell adhesion [21]. The combined actions of these chemicals likely leads to a more efficient removal of EC compared to trypLE select. While collagenase is also effective in denuding the EC layer, it was not used in this study. Collagenase mechanism of action involves breaking down collagen protein in the ECM and thus inducing EC detachment and subsequently, denudation. However, this study employs trypsin over collagenase because it damages both SMC and vessel extracellular matrix, compromising the integrity and mechanical properties of the vessel [22].
Three-dimensional bioprinting of artificial ovaries by an extrusion-based method using gelatin-methacryloyl bioink
Published in Climacteric, 2022
T. Wu, Y. Y. Gao, J. Su, X. N. Tang, Q. Chen, L. W. Ma, J. J. Zhang, J. M. Wu, S. X. Wang
To further validate the performance of GelMA, the biological properties of its printed scaffold were evaluated. Using lyophilization, the water in the scaffolds was removed in the form of water vapor, leaving a solid structure (Figure 1(A)). The swelling behavior of GelMA is presented in Figure 1(B), and the equilibrium water content is 91.6%. Suitable degradation kinetics is necessary for cell growth in vivo, as structures that degrade too rapidly cannot maintain the cell microenvironment, while long-term existence of the grafts in vivo may cause chronic fibrosis and immune responses. Our results showed that collagenase accelerates the degradation of the 3D scaffolds (Figure 1(C)). Collagenases of type II and type IV degrade the structure within 80 min. However, nearly 75% remains after collagenase type I treatment. To test the printability of the bioink, we fabricated a complex structure in the shape of a crocodile (Figure 1(D)). Morphology observation revealed that the grids are continuous and form regular corners (Figure 1(E)), confirming that the printed scaffolds possess high shape fidelity.
Peyronie’s disease: pharmacological treatments and limitations
Published in Expert Review of Clinical Pharmacology, 2021
Eric V. Li, Robert Esterquest, Minh N. Pham, Evan J. Panken, Channa Amarasekera, Aisha Siebert, Petar Bajic, Laurence A. Levine
A variety of noninvasive and minimally invasive therapies exist for PD, but many options have been under-investigated and/or lacking in robust studies. For patients who are not indicated for or declining surgery, these interventions are an important treatment strategy for those with symptoms or bother. Intralesional collagenase remains the only FDA-approved treatment for PD but has been withdrawn from the market in the European Union, Canada and Australia. Many other therapies reviewed here, such as PTT and oral therapies, have been implemented into clinical practice, sometimes contrary to recommendations, due to their potential benefit and absence of risk. Because of the paucity of high-quality evidence, patients should be appropriately counseled about the risks and limitations of agents prior to initiation, especially those not recommended by professional guidelines.