scholarly journals Critical evaluation of the interaction of special proteins with human stratum corneum via terahertz scanning reflectometry and spectrometry

2019 ◽  
Vol 2 (2) ◽  
pp. 256-269 ◽  
Author(s):  
Kariah Crosby ◽  
Aunik Rahman ◽  
Kera F Crawford ◽  
Zia Shariat-Madar ◽  
Bozena Michniak-Kohn ◽  
...  
Keyword(s):  
Stratum Corneum ◽  
Membrane Surface ◽  
Critical Evaluation ◽  
Low Frequency ◽  
Coagulation Factor ◽  
Factor Xii ◽  
Surface Compound ◽  
Diffusion Kinetics ◽  
Human Stratum Corneum

Many patients with chronic skin disease develop hemostatic abnormalities. The blood coagulation factor XII is a multifunctional protease, which is involved in thrombosis, fibrinolysis, and inflammatory processes. The aim of this investigation was to assess the autoactivation of FXII that leads to the generation of FXII fragments and their subsequent cell penetration compared to UM8190, a lipophilic selective prolyl carboxypeptidase inhibitor compound. Terahertz scanning reflectometry (TSR) and terahertz spectrometry (TS) were used to study the surface-mediated FXII activation, as well as penetration of the FXII and UM8190, their retardant property, diffusion kinetics and fragmentation profiles into human stratum corneum (SC). From the diffusion kinetics and profiling experiments it was found that FXII does not penetrate the SC but remains mostly on the surface. Compound UM8190 indicates penetration into the SC, as indicated by the increased reflected intensity of T-ray. The terahertz spectral analysis via absorbance spectra indicates that at a low frequency of 0.56 THz a prominent peak occurs due to water or moisture for the SC alone. This peak, however, exhibits a shift for post-diffusion samples of both FXII saturated SC and UM8190-saturated SC. This is indicative of adhesion of these proteins onto the SC. Though this process corroborates the binding of FXII to the cell membrane surface as reported in the in vitro findings, it does not appear to be activated and degraded. It was also found that there are a number of absorbance peaks characteristic for each molecule and these peaks are uniquely shifted relative to each other when compared with the SC alone. Thus, these absorbance peaks may be utilized for assigning identifying features of the protein and peptides in this present study. Further investigation will be conducted for assigning the absorbance peaks to the specific proteins and their resonances.

Human Skin Binding and Absorption of Contaminants from Ground and Surface Water During Swimming and Bathing

1989 ◽  
Vol 8 (5) ◽  
pp. 853-859 ◽  
Author(s):  
Ronald C. Wester ◽  
Howard I. Maibach
Keyword(s):  
Surface Water ◽  
Stratum Corneum ◽  
Human Skin ◽  
The Body ◽  
Water Soluble ◽  
Exposure Effect ◽  
Human Stratum Corneum ◽  
Water Dilution

Contaminants exist in ground and surface water. Human skin has the capacity to bind and then absorb these contaminants into the body during swimming and bathing. Powdered human stratum corneum will bind both lipid-soluble (alachlor, polychlorinated biphenyls [PCBs], benzene) and water-soluble (nitroaniline) chemicals. In vitro (human skin) and in vivo (Rhesus monkey) studies show that these chemicals readily distribute into skin, and then some of the chemical is absorbed into the body. Linearity in binding and absorption exists for nitroaniline over a 10-fold concentration range. Multiple exposure to benzene is at least cumulative. Binding and absorption can be significant for exposures as short as 30 min, and will increase with time. Absorption with water dilution increased for alachlor, but not for dinoseb. Soap reversed the partitioning of alachlor between human stratum corneum and water. The PCBs could be removed from skin by soap and water (70% efficiency) for up to 3 h and then decontamination potential decreased, due to continuing skin absorption. The model in vitro and in vivo systems used should permit easy estimation of this area of extensive human exposure effect on risk assessment.

scholarly journals The Effect of in Vivo Occlusion on Human Stratum Corneum Hydration-Dehydration in Vitro

1973 ◽  
Vol 61 (6) ◽  
pp. 375-379 ◽  
Author(s):  
Robert L. Anderson ◽  
Jean M. Cassidy ◽  
John R. Hansen ◽  
Wilbur Yellin
Keyword(s):  
Stratum Corneum ◽  
Human Stratum Corneum ◽  
Stratum Corneum Hydration

scholarly journals Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis

2006 ◽  
Vol 203 (3) ◽  
pp. 513-518 ◽  
Author(s):  
Christoph Kleinschnitz ◽  
Guido Stoll ◽  
Martin Bendszus ◽  
Kai Schuh ◽  
Hans-Ulrich Pauer ◽  
...  
Keyword(s):  
Thrombus Formation ◽  
Coagulation Factor ◽  
Artery Occlusion ◽  
Factor Xii ◽  
Intrinsic Pathway ◽  
Fibrin Formation ◽  
Vessel Injury ◽  
Normal Hemostasis ◽  
A Site

Formation of fibrin is critical for limiting blood loss at a site of blood vessel injury (hemostasis), but may also contribute to vascular thrombosis. Hereditary deficiency of factor XII (FXII), the protease that triggers the intrinsic pathway of coagulation in vitro, is not associated with spontaneous or excessive injury-related bleeding, indicating FXII is not required for hemostasis. We demonstrate that deficiency or inhibition of FXII protects mice from ischemic brain injury. After transient middle cerebral artery occlusion, the volume of infarcted brain in FXII-deficient and FXII inhibitor–treated mice was substantially less than in wild-type controls, without an increase in infarct-associated hemorrhage. Targeting FXII reduced fibrin formation in ischemic vessels, and reconstitution of FXII-deficient mice with human FXII restored fibrin deposition. Mice deficient in the FXII substrate factor XI were similarly protected from vessel-occluding fibrin formation, suggesting that FXII contributes to pathologic clotting through the intrinsic pathway. These data demonstrate that some processes involved in pathologic thrombus formation are distinct from those required for normal hemostasis. As FXII appears to be instrumental in pathologic fibrin formation but dispensable for hemostasis, FXII inhibition may offer a selective and safe strategy for preventing stroke and other thromboembolic diseases.

scholarly journals In vivo roles of factor XII

Blood ◽  
2012 ◽  
Vol 120 (22) ◽  
pp. 4296-4303 ◽  
Author(s):  
Thomas Renné ◽  
Alvin H. Schmaier ◽  
Katrin F. Nickel ◽  
Margareta Blombäck ◽  
Coen Maas
Keyword(s):  
Thrombus Formation ◽  
Coagulation Factor ◽  
Special Focus ◽  
Factor Xii ◽  
Excessive Bleeding ◽  
Charged Surfaces ◽  
Factor Xiia ◽  
Knockout Model

Abstract Coagulation factor XII (FXII, Hageman factor, EC = 3.4.21.38) is the zymogen of the serine protease, factor XIIa (FXIIa). FXII is converted to FXIIa through autoactivation induced by “contact” to charged surfaces. FXIIa is of crucial importance for fibrin formation in vitro, but deficiency in the protease is not associated with excessive bleeding. For decades, FXII was considered to have no function for coagulation in vivo. Our laboratory developed the first murine knockout model of FXII. Consistent with their human counterparts, FXII−/− mice have a normal hemostatic capacity. However, thrombus formation in FXII−/− mice is largely defective, and the animals are protected from experimental cerebral ischemia and pulmonary embolism. This murine model has created new interest in FXII because it raises the possibility for safe anticoagulation, which targets thrombosis without influence on hemostasis. We recently have identified platelet polyphosphate (an inorganic polymer) and mast cell heparin as in vivo FXII activators with implications on the initiation of thrombosis and edema during hypersensitivity reactions. Independent of its protease activity, FXII exerts mitogenic activity with implications for angiogenesis. The goal of this review is to summarize the in vivo functions of FXII, with special focus to its functions in thrombosis and vascular biology.

scholarly journals Overexpression of miR-24 Is Involved in the Formation of Hypocoagulation State after Severe Trauma by Inhibiting the Synthesis of Coagulation Factor X

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Lu-Jia Chen ◽  
Lian Yang ◽  
Xing Cheng ◽  
Yin-Kai Xue ◽  
Li-Bo Chen
Keyword(s):  
Negative Correlation ◽  
Major Trauma ◽  
Injury Severity ◽  
Coagulation Factor ◽  
In Vitro Study ◽  
Severe Trauma ◽  
Trauma Patients ◽  
Factor Xii ◽  
Factor X

Background. Dysregulation of microRNAs may contribute to the progression of trauma-induced coagulopathy (TIC). We aimed to explore the biological function that miRNA-24-3p (miR-24) might have in coagulation factor deficiency after major trauma and TIC. Methods. 15 healthy volunteers and 36 severe trauma patients (Injury Severity Score ≥ 16 were enrolled. TIC was determined as the initial international normalized ratio >1.5. The miR-24 expression and concentrations of factor X (FX) and factor XII in plasma were measured. In vitro study was conducted on L02 cell line. Results. The plasma miR-24 expression was significantly elevated by 3.17-fold (P=0.043) in major trauma patients and reduced after 3 days (P<0.01). The expression level was significantly higher in TIC than in non-TIC patients (P=0.040). Multivariate analysis showed that the higher miR-24 expression was associated with TIC. The plasma concentration of FX in TIC patients was significantly lower than in the non-TIC ones (P=0.030) and controls (P<0.01). A negative correlation was observed between miR-24 and FX. miR-24 transduction significantly reduced the FX level in the supernatant of L02 cells (P=0.030). Conclusions. miR-24 was overexpressed in major trauma and TIC patients. The negative correlation of miR-24 with FX suggested the possibility that miR-24 might inhibit the synthesis of FX during TIC.

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