scholarly journals Nonlinear optical microscopy is a novel tool for the analysis of cutaneous alterations in pseudoxanthoma elasticum

2020 ◽  
Vol 35 (8) ◽  
pp. 1821-1830 ◽  
Author(s):  
Norbert Kiss ◽  
Luca Fésűs ◽  
Szabolcs Bozsányi ◽  
Flóra Szeri ◽  
Matthias Van Gils ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Nonlinear Optical ◽  
Second Harmonic ◽  
Histopathological Examination ◽  
Pseudoxanthoma Elasticum ◽  
Calcium Deposition ◽  
Inorganic Pyrophosphate ◽  
Ectopic Mineralization ◽  
New Variant ◽  
Cardiovascular Assessment

Abstract Pseudoxanthoma elasticum (PXE, OMIM 264800) is a rare autosomal recessive disorder with ectopic mineralization and fragmentation of elastin fibers. It is caused by mutations of the ABCC6 gene that leads to decreased serum levels of inorganic pyrophosphate (PPi) anti-mineralization factor. The occurrence of severe complications among PXE patients highlights the importance of early diagnosis so that prompt multidisciplinary care can be provided to patients. We aimed to examine dermal connective tissue with nonlinear optical (NLO) techniques, as collagen emits second-harmonic generation (SHG) signal, while elastin can be excited by two-photon excitation fluorescence (TPF). We performed molecular genetic analysis, ophthalmological and cardiovascular assessment, plasma PPi measurement, conventional histopathological examination, and ex vivo SHG and TPF imaging in five patients with PXE and five age- and gender-matched healthy controls. Pathological mutations including one new variant were found in the ABCC6 gene in all PXE patients and their plasma PPi level was significantly lower compared with controls. Degradation and mineralization of elastin fibers and extensive calcium deposition in the mid-dermis was visualized and quantified together with the alterations of the collagen structure in PXE. Our data suggests that NLO provides high-resolution imaging of the specific histopathological features of PXE-affected skin. In vivo NLO may be a promising tool in the assessment of PXE, promoting early diagnosis and follow-up.

scholarly journals Therapeutics Development for Pseudoxanthoma Elasticum and Related Ectopic Mineralization Disorders: Update 2020

2020 ◽  
Vol 10 (1) ◽  
pp. 114
Author(s):  
Hongbin Luo ◽  
Qiaoli Li ◽  
Yi Cao ◽  
Jouni Uitto
Keyword(s):  
Plasma Levels ◽  
Autosomal Recessive Disorder ◽  
Pseudoxanthoma Elasticum ◽  
Calcium Hydroxyapatite ◽  
The Elderly ◽  
Arterial Calcification ◽  
Inorganic Pyrophosphate ◽  
Treatment Development ◽  
Arterial Blood ◽  
Ectopic Mineralization

Pseudoxanthoma elasticum (PXE), the prototype of heritable ectopic mineralization disorders, manifests with deposition of calcium hydroxyapatite crystals in the skin, eyes and arterial blood vessels. This autosomal recessive disorder, due to mutations in ABCC6, is usually diagnosed around the second decade of life. In the spectrum of heritable ectopic mineralization disorders are also generalized arterial calcification of infancy (GACI), with extremely severe arterial calcification diagnosed by prenatal ultrasound or perinatally, and arterial calcification due to CD73 deficiency (ACDC) manifesting with arterial and juxta-articular mineralization in the elderly; the latter disorders are caused by mutations in ENPP1 and NT5E, respectively. The unifying pathomechanistic feature in these three conditions is reduced plasma levels of inorganic pyrophosphate (PPi), a powerful endogenous inhibitor of ectopic mineralization. Several on-going attempts to develop treatments for these conditions, either with the goal to normalize PPi plasma levels or by means of preventing calcium hydroxyapatite deposition independent of PPi, are in advanced preclinical levels or in early clinical trials. This overview summarizes the prospects of treatment development for ectopic mineralization disorders, with PXE, GACI and ACDC as the target diseases, from the 2020 vantage point.

scholarly journals ABCC6, Pyrophosphate and Ectopic Calcification: Therapeutic Solutions

2021 ◽  
Vol 22 (9) ◽  
pp. 4555
Author(s):  
Briana K. Shimada ◽  
Viola Pomozi ◽  
Janna Zoll ◽  
Sheree Kuo ◽  
Ludovic Martin ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Genetic Disorders ◽  
Pseudoxanthoma Elasticum ◽  
Arterial Calcification ◽  
Ectopic Calcification ◽  
Direct Inhibition ◽  
Inorganic Pyrophosphate ◽  
Cardiovascular Tissues ◽  
Ectopic Mineralization

Pathological (ectopic) mineralization of soft tissues occurs during aging, in several common conditions such as diabetes, hypercholesterolemia, and renal failure and in certain genetic disorders. Pseudoxanthoma elasticum (PXE), a multi-organ disease affecting dermal, ocular, and cardiovascular tissues, is a model for ectopic mineralization disorders. ABCC6 dysfunction is the primary cause of PXE, but also some cases of generalized arterial calcification of infancy (GACI). ABCC6 deficiency in mice underlies an inducible dystrophic cardiac calcification phenotype (DCC). These calcification diseases are part of a spectrum of mineralization disorders that also includes Calcification of Joints and Arteries (CALJA). Since the identification of ABCC6 as the “PXE gene” and the development of several animal models (mice, rat, and zebrafish), there has been significant progress in our understanding of the molecular genetics, the clinical phenotypes, and pathogenesis of these diseases, which share similarities with more common conditions with abnormal calcification. ABCC6 facilitates the cellular efflux of ATP, which is rapidly converted into inorganic pyrophosphate (PPi) and adenosine by the ectonucleotidases NPP1 and CD73 (NT5E). PPi is a potent endogenous inhibitor of calcification, whereas adenosine indirectly contributes to calcification inhibition by suppressing the synthesis of tissue non-specific alkaline phosphatase (TNAP). At present, therapies only exist to alleviate symptoms for both PXE and GACI; however, extensive studies have resulted in several novel approaches to treating PXE and GACI. This review seeks to summarize the role of ABCC6 in ectopic calcification in PXE and other calcification disorders, and discuss therapeutic strategies targeting various proteins in the pathway (ABCC6, NPP1, and TNAP) and direct inhibition of calcification via supplementation by various compounds.

scholarly journals Diffuse leptomeningeal glioneuronal tumor with high-grade features masquerading as tubercular meningitis—a case report

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Sameer Peer ◽  
Vivek Murumkar ◽  
Karthik Kulanthaivelu ◽  
Chandrajit Prasad ◽  
Shilpa Rao ◽  
...  
Keyword(s):  
Case Report ◽  
Early Diagnosis ◽  
Histopathological Examination ◽  
Glioneuronal Tumor ◽  
Communicating Hydrocephalus ◽  
High Grade ◽  
Endemic Region ◽  
Tubercular Meningitis ◽  
Leptomeningeal Enhancement ◽  
Diffuse Leptomeningeal Glioneuronal Tumor

Abstract Background Diffuse leptomeningeal glioneuronal tumor (DLGNT) has been recently described in the literature. The complete neuroimaging spectrum and histopathological characteristics of this entity are yet to be elucidated. In an endemic region, diffuse leptomeningeal enhancement on neuroimaging with associated communicating hydrocephalus is usually suggestive of infective meningitis and the patients are started on empirical anti-microbial therapy. However, it is important to consider other differential diagnosis of leptomeningeal enhancement in such cases, particularly if the clinical condition does not improve on anti-microbial therapy. An early diagnosis of a neoplastic etiology may be of particular importance as the treatment regimens vary considerably depending on the underlying disease condition. Case presentation In this case report, we describe a case of DLGNT with high-grade histopathological features which was initially managed as tubercular meningitis based on the initial neuroimaging findings. Due to worsening of the clinical course and subsequent imaging findings at follow-up, a diagnosis of DLGNT was considered and subsequently proven to be DLGNT with features of anaplasia on histopathological examination of leptomeningeal biopsy specimen. Conclusion This case highlights the importance of recognizing certain subtle finding on MRI which may help in an early diagnosis of DLGNT which is crucial for appropriate treatment.

scholarly journals Disruption of Abcc6 Transporter in Zebrafish Causes Ocular Calcification and Cardiac Fibrosis

2020 ◽  
Vol 22 (1) ◽  
pp. 278
Author(s):  
Jianjian Sun ◽  
Peilu She ◽  
Xu Liu ◽  
Bangjun Gao ◽  
Daqin Jin ◽  
...  
Keyword(s):  
Vitamin K ◽  
Cardiac Fibrosis ◽  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum ◽  
Matrix Gla Protein ◽  
Ectopic Calcification ◽  
Transcription Activator ◽  
Multisystem Disorder ◽  
Ectopic Mineralization ◽  
Extensive Calcification

Pseudoxanthoma elasticum (PXE), caused by ABCC6/MRP6 mutation, is a heritable multisystem disorder in humans. The progressive clinical manifestations of PXE are accompanied by ectopic mineralization in various connective tissues. However, the pathomechanisms underlying the PXE multisystem disorder remains obscure, and effective treatment is currently available. In this study, we generated zebrafish abcc6a mutants using the transcription activator-like effector nuclease (TALEN) technique. In young adult zebrafish, abcc6a is expressed in the eyes, heart, intestine, and other tissues. abcc6a mutants exhibit extensive calcification in the ocular sclera and Bruch’s membrane, recapitulating part of the PXE manifestations. Mutations in abcc6a upregulate extracellular matrix (ECM) genes, leading to fibrotic heart with reduced cardiomyocyte number. We found that abcc6a mutation reduced levels of both vitamin K and pyrophosphate (PPi) in the serum and diverse tissues. Vitamin K administration increased the gamma-glutamyl carboxylated form of matrix gla protein (cMGP), alleviating ectopic calcification and fibrosis in vertebrae, eyes, and hearts. Our findings contribute to a comprehensive understanding of PXE pathophysiology from zebrafish models.

scholarly journals Nonlinear optical microscopies (NOMs) and plasmon-enhanced NOMs for biology and 2D materials

Nanophotonics ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1341-1358
Author(s):  
Jialin Ma ◽  
Mengtao Sun
Keyword(s):  
Raman Scattering ◽  
Nonlinear Optical ◽  
Stimulated Raman Scattering ◽  
Second Harmonic ◽  
2D Materials ◽  
Research Progress ◽  
Two Photon ◽  
Two Dimensional Materials ◽  
Anti Stokes ◽  
Physical Principles

AbstractIn this review, we focus on the summary of nonlinear optical microscopies (NOMs), which are stimulated Raman scattering (SRS), coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), and two-photon excited fluorescence (TPEF). The introduction is divided into two parts: the principle of SRS, CARS, TPEF, and SHG and their application to biology and two-dimensional materials. We also introduce the connections and differences between them. We also discuss the principle of plasmon-enhanced NOM and its application in the above two aspects. This paper not only summarizes the research progress in the frontier but also deepens the readers’ understanding of the physical principles of these NOMs.

2D organic-inorganic hybrid perovskite materials for nonlinear optics

Nanophotonics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1787-1810 ◽  
Author(s):  
Xiao Han ◽  
Yongshen Zheng ◽  
Siqian Chai ◽  
Songhua Chen ◽  
Jialiang Xu
Keyword(s):  
Nonlinear Optical ◽  
Second Harmonic ◽  
Low Cost ◽  
Laser Pulses ◽  
Structural Features ◽  
Photon Absorption ◽  
Saturable Absorption ◽  
Research Attention ◽  
Inorganic Hybrid ◽  
Quantum Well Structures

AbstractTwo-dimensional (2D) organic-inorganic hybrid perovskites feature characteristics of inherent quantum-well structures and intriguing optoelectronic properties, and have therefore attracted enormous research attention for their optical applications in light emitting, sensing, modulation, and telecommunication devices. The low-cost and solution-processed fabrications as well as alternative organic spacer cations endue 2D hybrid perovskites with higher tunability in optical and photonic applications. In particular, they demonstrate distinguished nonlinear optical characters such as second-harmonic generation (SHG), two-photon absorption (2PA), and saturable absorption (SA) under the excitation of laser pulses. Here, we discuss the construction of the various sorts of 2D hybrid perovskites with different structural features. We have also highlighted some representative properties and applications of these 2D hybrid perovskites in both linear and nonlinear optical regimes.

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