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AIM: Biallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel hypoplasia, delayed/failed tooth eruption, intrapulpal calcifications, gingival hyperplasia and nephrocalcinosis. FAM20A binds to FAM20C, the Golgi casein kinase (GCK) and potentiates its function to phosphorylate secreted proteins critical for biomineralization. While many FAM20A pathogenic mutations have been reported, the pathogeneses of orodental anomalies in ERS remain to be elucidated. This study aimed to identify disease-causing mutations for patients with ERS phenotypes and to discern the molecular mechanism underlying ERS intrapulpal calcifications. METHODOLOGY: Phenotypic characterization and whole exome analyses were conducted for 8 families and 2 sporadic cases with hypoplastic AI. A minigene assay was performed to investigate the molecular consequences of a FAM20A splice-site variant. RNA sequencing followed by transcription profiling and gene ontology (GO) analyses were carried out for dental pulp tissues of ERS and the control. RESULTS: Biallelic FAM20A mutations were demonstrated for each affected individual, including 7 novel pathogenic variants: c.590-5T>A, c.625T>A (p.Cys209Ser), c.771del (p.Gln258Argfs*28), c.832_835delinsTGTCCGACGGTGTCCGACGGTGTC CA (p.Val278Cysfs*29), c.1232G>A (p.Arg411Gln), c.1297A>G (p.Arg433Gly) and c.1351del (p.Gln451Serfs*4). The c.590-5T>A splice-site mutation caused Exon 3 skipping, which resulted in an in-frame deletion of a unique region of the FAM20A protein, p.(Asp197_Ile214delinsVal). Analyses of differentially expressed genes in ERS pulp tissues demonstrated that genes involved in biomineralization, particularly dentinogenesis, were significantly upregulated, such as DSPP, MMP9, MMP20 and WNT10A. Enrichment analyses indicated overrepresentation of gene sets associated with BMP and SMAD signalling pathways. In contrast, GO terms related to inflammation and axon development were underrepresented. Among BMP signalling genes, BMP agonists GDF7, GDF15, BMP3, BMP8A, BMP8B, BMP4 and BMP6 were upregulated, while BMP antagonists GREM1, BMPER and VWC2 showed decreased expression in ERS dental pulp tissues. CONCLUSIONS: Upregulation of BMP signalling underlies intrapulpal calcifications in ERS. FAM20A plays an essential role in pulp tissue homeostasis and prevention of ectopic mineralization in soft tissues. This critical function probably depends upon MGP (matrix Gla protein), a potent mineralization inhibitor that must be properly phosphorylated by FAM20A-FAM20C kinase complex.
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Amelogênese Imperfeita , Calcinose , Proteínas do Esmalte Dentário , Nefrocalcinose , Humanos , Nefrocalcinose/genética , Nefrocalcinose/patologia , Amelogênese Imperfeita/genética , Amelogênese Imperfeita/metabolismo , Amelogênese Imperfeita/patologia , Polpa Dentária/metabolismo , Proteínas do Esmalte Dentário/genética , Mutação , Perfilação da Expressão Gênica , Proteínas de Transporte/genéticaRESUMO
OBJECTIVES: To investigate the presence of soft tissue calcifications in the head and neck region on panoramic radiographs of older adults. METHODS: We analysed 1176 panoramic radiographs obtained between January 2013 and December 2018 from individuals of both sexes aged 60 years or older, who were referred by dental specialities to the Dental Imaginology Service of the Federal University of Rio Grande do Norte, Brazil. The types of soft tissue calcification evaluated were as follows: carotid artery calcification (CAC), thyroid cartilage calcifications, triticeous cartilage calcifications, sialoliths, tonsilloliths and lymph node calcifications. The presence of soft tissue calcifications was correlated with age and sex. The chi-square test with continuity correction was used for the calculation of p values and the evaluation of the proposed associations. Prevalence ratios and 95% confidence intervals were also calculated. RESULTS: At least one type of soft tissue calcification was found in 43% of the sample. The main calcifications detected were CAC, thyroid and triticeous cartilage calcifications, tonsilloliths, sialoliths, calcified lymph nodes, and phleboliths. Mean patient age was 67.47 years and there was a predominance of females (62.8%) in the sample. Bivariate analysis showed a statistically significant association between female sex and the presence of thyroid and triticeous cartilage calcifications and between male sex and the presence of tonsilloliths. CONCLUSION: Routine panoramic radiography permits the identification of soft tissue calcifications that may be indicators of future cardiovascular disorders, the referral to a medical service and the establishment of therapies for stroke prevention.
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Calcinose , Cálculos das Glândulas Salivares , Idoso , Calcinose/diagnóstico por imagem , Calcinose/epidemiologia , Feminino , Humanos , Masculino , Pescoço , Prevalência , Radiografia PanorâmicaRESUMO
Inorganic phosphate is a vital constituent of cells and cell membranes, body fluids, and hard tissues. It is a major intracellular divalent anion, participates in many genetic, energy and intermediary metabolic pathways, and is important for bone health. Although we usually think of phosphate mostly in terms of its level in the serum, it is needed for many biological and structural functions of the body. Availability of adequate calcium and inorganic phosphate in the right proportions at the right place is essential for proper acquisition, biomineralization, and maintenance of mass and strength of the skeleton. The three specialized mineralized tissues, bones, teeth, and ossicles, differ from all other tissues in the human body because of their unique ability to mineralize, and the degree and process of mineralization in these tissues also differ to suit the specific functions: locomotion, chewing, and hearing, respectively. Biomineralization is a dynamic, complex, and lifelong process by which precipitations of inorganic calcium and inorganic phosphate divalent ions form biological hard tissues. Understanding the biomineralization process is important for the management of diseases caused by both defective and abnormal mineralization. Hypophosphatemia results in mineralization defects and osteomalacia, and hyperphosphatemia is implicated in abnormal excess calcification and/or ossification, but the exact mechanisms underlying these processes are not fully understood. In this review, we summarize available evidence on the role of phosphate in biomineralization. Other manuscripts in this issue of the journal deal with other relevant aspects of phosphate homeostasis, phosphate signaling and sensing, and disorders resulting from hypo- and hyperphosphatemic states.
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Biomineralização , Osso e Ossos/fisiologia , Fosfatos/fisiologia , Calcificação Fisiológica , Humanos , Hiperfosfatemia , HipofosfatemiaRESUMO
BACKGROUND: Steroid injections are among the most commonly used conservative treatments for lateral epicondylitis (LE). Although soft-tissue calcification has been reported as a steroid injection complication in certain tendons, such an association in LE has not been established. This study's purpose was to determine any association of both a history of steroid injection and the number of steroid injections with the types of calcification found in LE. METHODS: This study included 110 patients (110 elbows) with LE diagnosed from February 2016 to October 2017. We categorized calcifications seen on standard elbow radiographs as soft-tissue calcifications or enthesophytes using the classification of Shillito et al. Using logistic regression analyses, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for various factors possibly affecting calcification in LE: age, sex, body mass index, dominant-side involvement, occupation, symptom duration, hand-grip power, pain score on a visual analog scale, and treatment methods. The evaluated treatments included stretching exercise, extracorporeal shockwave therapy, and steroid injections. RESULTS: In the univariate analysis, the visual analog scale pain score, a history of steroid injection, and the number of steroid injections were significantly associated with soft-tissue calcification (P ≤ .020). In the multivariable analysis, a history of steroid injection (OR, 7.63; 95% CI, 1.63-35.72) and the number of steroid injections (OR, 1.18; 95% CI, 1.06-1.32) were significantly associated with soft-tissue calcification (P ≤ .010). CONCLUSIONS: The significant association of steroid injections with soft-tissue calcification in LE suggests that this calcification is likely to be an iatrogenic complication of steroid injection.
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Calcinose/induzido quimicamente , Entesopatia/induzido quimicamente , Esteroides/efeitos adversos , Cotovelo de Tenista/tratamento farmacológico , Adulto , Calcinose/diagnóstico por imagem , Entesopatia/diagnóstico por imagem , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Medição da Dor , Radiografia , Estudos Retrospectivos , Esteroides/administração & dosagem , Tendões/diagnóstico por imagemRESUMO
Metastatic calcification relates to abnormal calcification resulting from hypercalcaemia in otherwise normal tissues. Hypercalcaemia can occur secondary to chronic renal failure, hyperparathyroidism, hypervitaminosis D, and metastatic neoplasms. Specific symptoms are often lacking, but calcification may be a marker of disease severity and its chronicity. We present cases with different patterns of soft tissue calcification on Tc99m MDP bone scan.
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Calcinose/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Parede Torácica/diagnóstico por imagem , Idoso , Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Calcinose/etiologia , Carcinoma/complicações , Carcinoma/diagnóstico por imagem , Carcinoma/secundário , Feminino , Humanos , Hipercalcemia/complicações , Falência Renal Crônica , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Cintilografia , Compostos Radiofarmacêuticos , Medronato de Tecnécio Tc 99mRESUMO
RATIONALE: ABCC6 plays a crucial role in ectopic calcification; mutations of the gene cause pseudoxanthoma elasticum and general arterial calcification of infancy. To elucidate the role of ABCC6 in cellular physiology and disease, it is crucial to establish the exact subcellular localization of the native ABCC6 protein. OBJECTIVE: In a recent article in Circulation Research, ABCC6 was reported to localize to the mitochondria-associated membrane and not the plasma membrane. As the suggested mitochondrial localization is inconsistent with published data and the presumed role of ABCC6, we performed experiments to determine the cellular localization of ABCC6 in its physiological environment. METHODS AND RESULTS: We performed immunofluorescent labeling of frozen mouse and human liver sections, as well as primary hepatocytes. We used several different antibodies recognizing human and mouse ABCC6. Our results unequivocally show that ABCC6 is in the basolateral membrane of hepatocytes and is not associated with the mitochondria, mitochondria-associated membrane, or the endoplasmic reticulum. CONCLUSIONS: Our findings support the model that ABCC6 is in the basolateral membrane, mediating the sinusoidal efflux of a metabolite from the hepatocytes to systemic circulation.
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Transportadores de Cassetes de Ligação de ATP/metabolismo , Membrana Celular/metabolismo , Hepatócitos/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Biomarcadores/metabolismo , Polaridade Celular/fisiologia , Retículo Endoplasmático/metabolismo , Imunofluorescência , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
Commonly associated with autoimmune and renal disorders, calcinosis cutis is a disorder of systemic calcium deposition in soft tissues. The pathophysiology of such deposition varies based on subtype, therefore treatment options vary not only in terms of severity of disease but also with subtype. This case report describes a 52-year-old female with systemic sclerosis and an extensive past medical history who initially presented with complaints of worsening left lower leg pain, a negative workup for deep vein thrombosis, and an extensive palpable mass in the posterior thigh with erythema, drainage, and purulence. With multiple treatment options exhausted from her autoimmune disorders, she ultimately required surgical resection for her refractory infected calcinosis cutis. Identification of calcinosis cutis subtype in conjunction with appropriate history and physical is crucial to determining indications for treatment.
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Soft tissue calcifications frequently cause debilitating pain and functional impairments, considerably affecting patients' quality of life. As they are rare entities, evidence remains sparse, especially regarding treatment effectiveness and recurrence rates. While both pharmacological and surgical treatments may alleviate symptoms, complete resection is currently believed to prevent long-term recurrence of deposits. To improve understanding and raise awareness for soft tissue calcifications, the goal of this study was to review the current state of treatment and to compare benefits and possibilities of flap reconstruction versus simple excision in improving quality of life. Furthermore, we include a successful case report of complete resolution of symptoms following quadruple perforator flap reconstruction. By systematic literature review, studies published in MEDLINE between 1980 and 2024 reporting on surgical treatment and outcome of soft tissue calcifications were included, in addition to a detailed description of our case report. A total of 53 studies reporting on 197 patients with soft tissue calcifications were included. Simple surgical excision was the most commonly (85.9%) employed procedure, demonstrating a substantial recurrence rate of 13.3%. In contrast, no patients who underwent radical excision experienced recurrence. Dermal matrix grafts and flap reconstruction were successfully used in patients requiring substantial tissue coverage, highlighting their value in complex defect reconstruction following radical excision. The combination of complete surgical resection and flap reconstruction reduces recurrence rates and improves postoperative outcomes and quality of life of these patients, supporting early radical surgical intervention as the gold standard treatment for soft tissue calcifications.
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Calcinose , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Humanos , Calcinose/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Qualidade de Vida , Resultado do Tratamento , Masculino , Feminino , Pessoa de Meia-Idade , Dor/cirurgia , Dor/etiologiaRESUMO
Background In this study, we aimed to determine the prevalence and radiographic features of incidental head and neck soft tissue calcifications (STCs) on panoramic imagesand assess their clinical significance. Methodology Following well-established training and calibration procedures, 9,553 digital panoramic radiographs (DPRs) taken between January 1, 2021, and January 31, 22, were retrospectively evaluated. Only obvious calcifications and clear differential diagnoses were considered. The presence, type, side (i.e., unilateral or bilateral), number (single or multiple), and the presence of different calcifications in the same individual were recorded. STCs were recorded according to age and gender. Data were analyzed using the chi-square test and Fisher's exact test using SPSS version 18.0 (IBM Corp., Armonk, NY, USA). Results Overall, 35.8% of the DPRs studied showed the presence of STCs, including ossified stylohyoid complex (OSHC) (10.3%), thyroid cartilage (9.8%), tonsillolith (9.2%), atherosclerotic plaques (5.8%), calcified triticeous cartilage (CTC) (5.1%), sialolith (1.9%), as well as intra-articular (1.3%) and other calcifications (0.1-0.8%), i.e., calcified lymph node, antrolith, rhinolith, phlebolith, and osteoma cutis. STCs were found to be more prevalent in middle-aged patients and in females. A significant relationship was identified between the presence of carotid artery calcification and calcified superior horn of thyroid cartilage (CSHTC), as well as between the presence of CSHTC and CTC. Calcifications were detected either bilaterally (n = 2,003) or unilaterally (n = 2,388); however, OSHC mostly showed bilateral calcifications (8.5%). Conclusions Panoramic radiographs of dental patients reveal the frequent occurrence of STCs in the head and neck region with differing radiographic features. Certain calcifications show gender and age differences. Accurate detection of STCs may guide the identification of potential underlying diseases and help initiate referral to the relevant multidisciplinary teams.
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The vitamin D receptor (VDR) is expressed most abundantly in osteoblasts and osteocytes (osteoblastic cells) in bone tissues and regulates bone resorption and calcium (Ca) and phosphate (P) homeostasis in association with parathyroid hormone (PTH). We previously reported that near-physiological doses of vitamin D compounds suppressed bone resorption through VDR in osteoblastic cells. We also found that supra-physiological doses of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] induced bone resorption and hypercalcemia via VDR in osteoblastic cells. Here, we report that the latter, a proresorptive dose of 1,25(OH)2D3, causes soft tissue calcification through VDR in osteoblastic cells. High concentrations of vitamin D affect multiple organs and cause soft tissue calcification, with increases in bone resorption and serum Ca levels. Such a variety of symptoms is known as hypervitaminosis D, which is caused by not only high doses of vitamin D but also impaired vitamin D metabolism and diseases that produce 1,25(OH)2D3 ectopically. To clarify the biological process hierarchy in hypervitaminosis D, a proresorptive dose of 1,25(OH)2D3 was administered to wild-type mice in which bone resorption had been suppressed by neutralizing anti-receptor activator of NF-κB ligand (RANKL) antibody. 1,25(OH)2D3 upregulated the serum Ca x P product, concomitantly induced calcification of the aorta, lungs, and kidneys, and downregulated serum PTH levels in control IgG-pretreated wild-type mice. Pretreatment of wild-type mice with anti-RANKL antibody did not affect the down-regulation of PTH levels by 1,25(OH)2D3, but inhibited the increase of the serum Ca x P product and soft tissue calcification induced by 1,25(OH)2D3. Consistent with the effects of anti-RANKL antibody, VDR ablation in osteoblastic cells also did not affect the down-regulation of PTH levels by 1,25(OH)2D3, but suppressed the 1,25(OH)2D3-induced increase of the serum Ca x P product and calcification of soft tissues. Taken together with our previous results, these findings suggest that bone resorption induced by VDR signaling in osteoblastic cells is critical for the pathogenesis of hypervitaminosis D, but PTH is not involved in hypervitaminosis D.
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Fenômenos Biológicos , Receptores de Calcitriol , Camundongos , Animais , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Hormônio Paratireóideo/metabolismo , Calcitriol/metabolismo , Vitamina D/farmacologia , Vitamina D/metabolismo , Vitaminas/farmacologiaRESUMO
The characteristic radiological appearances of metabolic bone and soft tissue diseases in chronic renal failure are described and illustrated in the context of advancing understanding of the complex metabolic changes that occur in chronic kidney disease and its management.
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Distúrbio Mineral e Ósseo na Doença Renal Crônica , Insuficiência Renal Crônica , Osso e Ossos , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Humanos , Insuficiência Renal Crônica/diagnóstico por imagemRESUMO
Severely injured patients are beleaguered by complications during convalescence, such as dysregulated biomineralization. Paradoxically, severely injured patients experience the loss of bone (osteoporosis), resulting in diminished skeletal integrity and increased risk of fragility fractures; yet they also accrue mineralization in soft tissues, resulting in complications such as heterotopic ossification (HO). The pathophysiology leading to dysregulated biomineralization in severely injured patients is not well defined. It has been postulated that these pathologies are linked, such that mineralization is "transferred" from the bone to soft tissue compartments. The goal of this study was to determine if severe injury-induced osteoporosis and soft tissue calcification are temporally coincident following injury. Using a murine model of combined burn and skeletal muscle injury to model severe injury, it was determined that mice developed significant progressive bone loss, detectable as early as 3 days post injury, and marked soft tissue mineralization by 7 days after injury. The observed temporal concordance between the development of severe injury-induced osteoporosis and soft tissue mineralization indicates the plausibility that these complications share a common pathophysiology, though further experiments are required.
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BACKGROUND: The molecular etiology of Pseudoxanthoma Elasticum (PXE), an autosomal recessive connective tissue disorder, has become increasingly complex as not only mutations in the ABCC6, but also in ENPP1 and GGCX, can cause resembling phenotypes. METHODS: To get insights on the common pathway, the overlapping metabolites for these three proteins were predicted through 3D homology modeling and virtual screening. 3D homology models of ABCC6, ENPP1, and GGCX were generated by the MODELLER program, which were further validated using RAMPAGE and ERRAT servers. Substrate binding sites of ABCC6 were predicted using blind docking of reported in vitro substrates. RESULTS: Virtual screening against the substrate binding site of ABCC6 using metabolites listed in Human Metabolome Databases (HMDB) revealed the best possible substrate of ABCC6. Those listed metabolites were further docked against predicted substrate binding sites of GGCX and ENPP1. Molecular docking and virtual screening revealed a list of 133 overlapping metabolites of these three proteins. Most of them are Phosphatidylinositol (PI), Phosphatidylserine (PS), Diacylglycerol (DAG), phosphatidic acid, oleanolic acid metabolites and were found to have links with calcification. CONCLUSION: These predicted overlapping metabolites may give novel insights for searching common pathomechanism for PXE and PXE-like diseases.
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Carbono-Carbono Ligases/metabolismo , Metaboloma , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Pseudoxantoma Elástico , Pirofosfatases/metabolismo , Sítios de Ligação , Carbono-Carbono Ligases/genética , Humanos , Metaboloma/genética , Simulação de Acoplamento Molecular , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Mutação , Fenótipo , Diester Fosfórico Hidrolases/genética , Pseudoxantoma Elástico/genética , Pseudoxantoma Elástico/metabolismo , Pirofosfatases/genética , Homologia Estrutural de Proteína , Especificidade por SubstratoRESUMO
STATEMENT OF THE PROBLEM: Most of the soft tissue calcifications within the head and neck region might not be accompanied by clinical symptoms but may indicate some pathological conditions. PURPOSE: The aim of this research was to determine the prevalence of soft tissue calcifications in cone beam computed tomography (CBCT) images of mandibular region. MATERIALS AND METHOD: In this cross sectional study the CBCT images of 602 patients including 294 men and 308 women with mean age 41.38±15.18 years were evaluated regarding the presence, anatomical location; type (single or multiple) and size of soft tissue calcification in mandibular region. All CBCT images were acquired by NewTom VGi scanner. Odds ratio and chi-square tests were used for data analysis and p< 0.05 was considered to be statistically significant. RESULTS: 156 out of 602 patients had at least one soft tissue calcification in their mandibular region (25.9%. of studied population with mean age 51.7±18.03 years). Men showed significantly higher rate of soft tissue calcification than women (30.3% vs. 21.8%). Soft tissue calcification was predominantly seen at posterior region of the mandible (88%) and most of them were single (60.7%). The prevalence of soft tissue calcification increased with age. Most of the detected soft tissue calcifications were smaller than 3mm (90%). CONCLUSION: Soft tissue calcifications in mandibular area were a relatively common finding especially in posterior region and more likely to happen in men and in older age group.
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BACKGROUND: Dystrophic calcification can occur in any soft tissue with the absence of a systemic mineral imbalance and is often associated with trauma, infection, or inflammation. It is easily found in the site of the heart and skeletal muscles and rarely appears in the head and neck area. CASE REPORT: We present a rare case of multiple calcified masses in the left masseter muscle of a 26-year-old female with a history of trauma in the area. In computed tomography, multiple radiopaque masses were observed inside the left masseter muscle and blood test results were normal. The calcified masses were diagnosed as dystrophic calcification and removed by surgery without any complications. CONCLUSION: Different types of calcifications may occur in the cheek area, and they need to be distinguished from dystrophic calcification. Thorough clinical examination and history taking is required together with blood testing and radiographic examinations.
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This paper sets out in vitro protocols for studying the relative effectiveness of chelators used in the dissolution-based treatment of hard calcinosis. Pulverized hard calcinosis samples from human donors or synthetic hydroxyapatite nanoparticles were deposited by electrophoretic deposition on the surface of a quartz crystal microbalance sensor. Over 150 deposits of <20 µg were dissolved over the course of 1 h by aliquots of buffered, aqueous solutions of two calcium chelators, EDTA and citrate, with the surface-limited dissolution kinetics monitored with <1 s time resolution. There was no statistically significant difference in dissolution rate between the four synthetic hydroxyapatite materials in EDTA, but the dissolution rates in citrate were lower for hydroxyapatite produced by acetate or nitrate metathesis. Hard calcinosis and synthetic hydroxyapatites showed statistically identical dissolution behavior, meaning that readily available synthetic mimics can replace the rarer samples of biological origin in the development of calcinosis treatments. EDTA dissolved the hydroxyapatite deposits more than twice as fast as citrate at pH 7.4 and 37 °C, based on a first-order kinetic analysis of the initial frequency response. EDTA chelated 6.5 times more calcium than an equivalent number of moles of citrate. Negative controls using nonchelating N,N,N',N'-tetraethylethylenediamine (TEEDA) showed no dissolution effect. Pharmaceutical dissolution testing of synthetic hydroxyapatite tablets over 6 h showed that EDTA dissolved the tablets four to nine times more quickly than citrate.
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Técnicas de Microbalança de Cristal de Quartzo , Calcinose , Humanos , Hidroxiapatitas , Cinética , SolubilidadeRESUMO
Werner syndrome (i.e., adult progeria) is a rare autosomal recessive disorder caused by mutations of the WRN gene, which is characterized by the premature appearance of features associated with normal aging and cancer predisposition. Patients with Werner syndrome can present with musculoskeletal complaints, associated with suggestive radiographic features with a potential prognostic or therapeutic impact. This review illustrates the main radiographic features of Werner syndrome, focusing on the musculoskeletal system, such as soft-tissue calcification, muscular atrophy, osteoporosis, foot deformities, osteitis and osteomyelitis, and bone or soft-tissues malignancies. The identification of these features by radiologists can therefore be useful in the clinical screening of Werner syndrome.
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Doenças Musculoesqueléticas/diagnóstico por imagem , Doenças Musculoesqueléticas/etiologia , Síndrome de Werner/complicações , Humanos , RadiografiaRESUMO
Various disorders including pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI), which are caused by inactivating mutations in ABCC6 and ENPP1, respectively, present with extensive tissue calcification due to reduced plasma pyrophosphate (PPi). However, it has always been assumed that the bioavailability of orally administered PPi is negligible. Here, we demonstrate increased PPi concentration in the circulation of humans after oral PPi administration. Furthermore, in mouse models of PXE and GACI, oral PPi provided via drinking water attenuated their ectopic calcification phenotype. Noticeably, provision of drinking water with 0.3 mM PPi to mice heterozygous for inactivating mutations in Enpp1 during pregnancy robustly inhibited ectopic calcification in their Enpp1-/- offspring. Our work shows that orally administered PPi is readily absorbed in humans and mice and inhibits connective tissue calcification in mouse models of PXE and GACI PPi, which is recognized as safe by the FDA, therefore not only has great potential as an effective and extremely low-cost treatment for these currently intractable genetic disorders, but also in other conditions involving connective tissue calcification.
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Difosfatos/uso terapêutico , Pseudoxantoma Elástico/tratamento farmacológico , Calcificação Vascular/tratamento farmacológico , Transportadores de Cassetes de Ligação de ATP/deficiência , Transportadores de Cassetes de Ligação de ATP/genética , Administração Oral , Adulto , Idoso , Animais , Cálcio/análise , Tecido Conjuntivo/metabolismo , Difosfatos/sangue , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Miocárdio/química , Miocárdio/metabolismo , Diester Fosfórico Hidrolases/deficiência , Diester Fosfórico Hidrolases/genética , Gravidez , Pseudoxantoma Elástico/patologia , Pirofosfatases/deficiência , Pirofosfatases/genética , Calcificação Vascular/patologia , Adulto JovemRESUMO
Introduction: Heterotopic ossification involves the formation of trabecular bone outside of its usual anatomic location. While it is a well-known entity in orthopedic and spinal injury literature, it has also been observed after midline laparotomy and severe burns. Methods/Case Report: We present a case of a 69-year-old man who presented for ventral hernia repair after a prolonged postoperative course following colectomy involving an open abdomen with eventual closure with skin grafting. Results: Two large calcified objects were encountered during the excision of the skin graft from the small intestine and during the component separation. They had grown into the anterior fascia and rectus muscle and interdigitated between loops of the small bowel. After careful resection of the 2 calcified objects, a ventral hernia repair with a component separation was successfully performed. Pathology was consistent with heterotopic ossification. After 18 months, there was no clinical evidence of recurrence. Discussion: Heterotopic ossification is not frequently encountered during ventral hernia repairs, but its presence can complicate repair. Resection is the only option in the context of hernia repair. If recognized preoperatively, waiting up to a year for the bone to mature before excision has been suggested, but there is minimal data to support this. Consultation with a general surgeon is also advised in case the calcified tissue involves the underlying viscera.
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Bone scintigraphy (BS) is a well--established commonly used imaging modality for staging and follow--up evaluation of cancer patients. Occasionally, BS may show asymptomatic unusual extraosseous lesions in the body which may or may not be related to primary disease. We here present an interesting case of carcinoma cervix in whom 18F sodium fluoride positron emission tomography-computerized tomography (PET-CT) bone scan detected an intracranial lesion. Initially, this lesion was suspected as brain metastasis; however, later on, combined PET--CT images and contrast-enhanced CT confirmed this lesion as calcified falcine meningioma in the right posterior parietal region.