scholarly journals From organic and inorganic phosphates to valvular and vascular calcifications

2021 ◽  
Author(s):  
Magnus Bäck ◽  
Jean-Baptiste Michel

Abstract Calcification of the arterial wall and valves is an important part of the pathophysiological process of peripheral and coronary atherosclerosis, aortic stenosis, ageing, diabetes, and chronic kidney disease. This review aims to better understand how extracellular phosphates and their ability to be retained as calcium phosphates on the extracellular matrix initiate the mineralization process of arteries and valves. In this context, the physiological process of bone mineralization remains a human model for pathological soft tissue mineralization. Soluble (ionized) calcium precipitation occurs on extracellular phosphates; either with inorganic or on exposed organic phosphates. Organic phosphates are classified as either structural (phospholipids, nucleic acids) or energetic (corresponding to phosphoryl transfer activities). Extracellular phosphates promote a phenotypic shift in vascular smooth muscle and valvular interstitial cells towards an osteoblast gene expression pattern, which provokes the active phase of mineralization. A line of defense systems protects arterial and valvular tissue calcifications. Given the major roles of phosphate in soft tissue calcification, phosphate mimetics, and/or prevention of phosphate dissipation represent novel potential therapeutic approaches for arterial and valvular calcification.

Author(s):  
Elisa Mazzoni ◽  
Maria Rosa Iaquinta ◽  
Carmen Lanzillotti ◽  
Chiara Mazziotta ◽  
Martina Maritati ◽  
...  

Over the past decades, age-related pathologies have increased abreast the aging population worldwide. The increased age of the population indicates that new tools, such as biomaterials/scaffolds for damaged tissues, which display high efficiency, effectively and in a limited period of time, for the regeneration of the body's tissue are needed. Indeed, scaffolds can be used as templates for three-dimensional tissue growth in order to promote the tissue healing stimulating the body's own regenerative mechanisms. In tissue engineering, several types of biomaterials are employed, such as bioceramics including calcium phosphates, bioactive glasses, and glass–ceramics. These scaffolds seem to have a high potential as biomaterials in regenerative medicine. In addition, in conjunction with other materials, such as polymers, ceramic scaffolds may be used to manufacture composite scaffolds characterized by high biocompatibility, mechanical efficiency and load-bearing capabilities that render these biomaterials suitable for regenerative medicine applications. Usually, bioceramics have been used to repair hard tissues, such as bone and dental defects. More recently, in the field of soft tissue engineering, this form of scaffold has also shown promising applications. Indeed, soft tissues are continuously exposed to damages, such as burns or mechanical traumas, tumors and degenerative pathology, and, thereby, thousands of people need remedial interventions such as biomaterials-based therapies. It is known that scaffolds can affect the ability to bind, proliferate and differentiate cells similar to those of autologous tissues. Therefore, it is important to investigate the interaction between bioceramics and somatic/stem cells derived from soft tissues in order to promote tissue healing. Biomimetic scaffolds are frequently employed as drug-delivery system using several therapeutic molecules to increase their biological performance, leading to ultimate products with innovative functionalities. This review provides an overview of essential requirements for soft tissue engineering biomaterials. Data on recent progresses of porous bioceramics and composites for tissue repair are also presented.


1998 ◽  
Vol 76 (5) ◽  
pp. 589-597 ◽  
Author(s):  
Pang N Shek ◽  
Roy J Shephard

An inflammatory response represents a fundamental series of humoral and cellular reaction cascades in response to infection, tissue injury, and related insults. An excessive response is commonly seen under the pathological conditions of trauma, sepsis, and burns. It is becoming increasingly evident that most, if not all, of the distinguishing features of a classical inflammatory response are detectable in an exercising individual, namely mobilization and activation of granulocytes, lymphocytes, and monocytes; release of inflammatory factors and soluble mediators; involvement of active phase reactants; and activation of the complement and other reactive humoral cascade systems. While the manifestation of many exercise-induced immune and related changes has been reported and confirmed repeatedly, the underlying mechanisms triggering and modulating the elicited immune responses are, at best, poorly understood. Unlike the exaggerated and sometimes uncontrollable inflammatory response in septic and trauma patients resulting in morbidity and mortality, strenuous and severe exercise normally elicits an inflammatory response of a subclinical nature to facilitate the repairing process for site-specific tissue damage. Regardless of the inciting event, for example trauma, infection, or exercise, and given an appropriate triggering signal, a remarkably similar sequence of inflammatory reactions can be reproduced in the affected host. Therefore, physical exercise and training represent an acceptable and good model for the study of limited inflammatory responses in humans.Key words: trauma, infection, exercise, inflammatory response, cytokines.


2020 ◽  
Vol 11 (1) ◽  
pp. 145
Author(s):  
Othman Laban ◽  
Elsadig Mahdi ◽  
John-John Cabibihan

Common quantitative assessments of neck injury criteria do not predict anatomical neck injuries and lack direct relations to design parameters of whiplash-protection systems. This study aims to provide insights into potential soft tissue-level injury sites based on the interactions developed in-between different anatomical structures in case of a rear-end collision. A detailed finite element human model has exhibited an excellent biofidelity when validated against volunteer impacts. Three head restraint arrangements were simulated, predicting both the kinematic response and the anatomical pain source at each arrangement. Head restraint’s contribution has reduced neck shear and head kinematics by at least 70 percent, minimized pressure gradients acting on ganglia and nerve roots less than half. Posterior column ligaments were the most load-bearing components, followed by the lower intervertebral discs and upper capsular ligaments. Sprain of the interspinous ligamentum flavum at early stages has caused instability in the craniovertebral structure causing its discs and facet joints to be elevated compressive loads. Excessive hyperextension motion, which occurred in the absence of the head restraint, has promoted a stable avulsion teardrop fracture of the fourth vertebral body’s anteroinferior aspect and rupture the anterior longitudinal ligament. The observed neck injuries can be mathematically related to head–torso relative kinematics. These relations will lead to the development of a comprehensive neck injury criterion that can predict the injury level. This, in turn, will impose a significant impact on the design processes of vehicle anti-whiplash safety equipment.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 507 ◽  
Author(s):  
Geanina Voicu ◽  
Daniela Rebleanu ◽  
Cristina Ana Constantinescu ◽  
Elena Valeria Fuior ◽  
Letitia Ciortan ◽  
...  

Calcific aortic valve disease (CAVD) is a progressive disorder that increases in prevalence with age. An important role in aortic valve calcification is played by valvular interstitial cells (VIC), that with age or in pathological conditions acquire an osteoblast-like phenotype that advances the disease. Therefore, pharmacological interventions aiming to stop or reverse the osteoblastic transition of VIC may represent a therapeutic option for CAVD. In this study, we aimed at developing a nanotherapeutic strategy able to prevent the phenotypic switch of human aortic VIC into osteoblast-like cells. We hypothesize that nanocarriers designed for silencing the Runt-related transcription factor 2 (Runx2) will stop the progress or reverse the osteodifferentiation of human VIC, induced by high glucose concentrations and pro-osteogenic factors. We report here the potential of fullerene (C60)-polyethyleneimine (PEI)/short hairpin (sh)RNA-Runx2 nano-polyplexes to efficiently down-regulate Runx2 mRNA and protein expression leading subsequently to a significant reduction in the expression of osteogenic proteins (i.e., ALP, BSP, OSP and BMP4) in osteoblast-committed VIC. The data suggest that the silencing of Runx2 could represent a novel strategy to impede the osteoblastic phenotypic shift of VIC and the ensuing progress of CAVD.


Proceedings ◽  
2020 ◽  
Vol 36 (1) ◽  
pp. 200
Author(s):  
Rob Dixon ◽  
Stephen Anderson ◽  
Lisa Kidd ◽  
Mary Fletcher

Nutritional deficiency of phosphorus (P) is a major constraint to productivity of cattle grazing many tropical rangelands with low P soils, particularly in northern Australia, South America and Africa. Cattle growth and reproductive rates may be severely reduced. Such P deficiency is usually addressed by providing supplements containing calcium phosphates. In the seasonally dry tropics such supplements are most effective when fed during the summer rainy season when the pasture quality as energy and protein are highest. Young cattle often continue to grow slowly when P deficient, but with reduced bone mineralization. Cows with normally high bone mineral reserves (from previously P-adequate diets) can mobilize bone P during late pregnancy and lactation when diet P is insufficient. This mobilization may contribute up to ca. one-third of the P requirements and allow P-deficient cows to maintain milk production and calf growth, but is associated with reduced pasture intake and severe loss of cow liveweight. Cows can replenish bone minerals when P intake exceeds immediate requirements for growth and milk. Since on large commercial farms in rangelands it is often difficult to effectively implement P supplementation of cattle during the rainy season the mobilization and replenishment of body mineral reserves are important for managing P nutrition through the annual cycle. Biochemical markers in blood are valuable for diagnosis of P deficiency in grazing cattle. In conclusion, understanding of the nutritional physiology of cattle provides opportunities to improve management of P nutrition of cattle grazing P deficient rangelands and alleviating production losses.


Author(s):  
D. C. Swartzendruber ◽  
Norma L. Idoyaga-Vargas

The radionuclide gallium-67 (67Ga) localizes preferentially but not specifically in many human and experimental soft-tissue tumors. Because of this localization, 67Ga is used in clinical trials to detect humar. cancers by external scintiscanning methods. However, the fact that 67Ga does not localize specifically in tumors requires for its eventual clinical usefulness a fuller understanding of the mechanisms that control its deposition in both malignant and normal cells. We have previously reported that 67Ga localizes in lysosomal-like bodies, notably, although not exclusively, in macrophages of the spocytaneous AKR thymoma. Further studies on the uptake of 67Ga by macrophages are needed to determine whether there are factors related to malignancy that might alter the localization of 67Ga in these cells and thus provide clues to discovering the mechanism of 67Ga localization in tumor tissue.


Author(s):  
J. P. Brunschwig ◽  
R. M. McCombs ◽  
R. Mirkovic ◽  
M. Benyesh-Melnick

A new virus, established as a member of the herpesvirus group by electron microscopy, was isolated from spontaneously degenerating cell cultures derived from the kidneys and lungs of two normal tree shrews. The virus was found to replicate best in cells derived from the homologous species. The cells used were a tree shrew cell line, T-23, which was derived from a spontaneous soft tissue sarcoma. The virus did not multiply or did so poorly for a limited number of passages in human, monkey, rodent, rabbit or chick embryo cells. In the T-23 cells, the virus behaved as members of the subgroup B of herpesvirus, in that the virus remained primarily cell associated.


Author(s):  
Alexis T. Bell

Heterogeneous catalysts, used in industry for the production of fuels and chemicals, are microporous solids characterized by a high internal surface area. The catalyticly active sites may occur at the surface of the bulk solid or of small crystallites deposited on a porous support. An example of the former case would be a zeolite, and of the latter, a supported metal catalyst. Since the activity and selectivity of a catalyst are known to be a function of surface composition and structure, it is highly desirable to characterize catalyst surfaces with atomic scale resolution. Where the active phase is dispersed on a support, it is also important to know the dispersion of the deposited phase, as well as its structural and compositional uniformity, the latter characteristics being particularly important in the case of multicomponent catalysts. Knowledge of the pore size and shape is also important, since these can influence the transport of reactants and products through a catalyst and the dynamics of catalyst deactivation.


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