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Systemic vasculitides are a rare and complex group of diseases that can affect multiple organ systems. Clinically, presentation may be vague and non-specific and as such, diagnosis and subsequent management are challenging. These entities are typically classified by the size of vessel involved, including large-vessel vasculitis (giant cell arteritis, Takayasu's arteritis, and clinically isolated aortitis), medium-vessel vasculitis (including polyarteritis nodosa and Kawasaki disease), and small-vessel vasculitis (granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis). There are also other systemic vasculitides that do not fit in to these categories, such as Behcet's disease, Cogan syndrome, and IgG4-related disease. Advances in medical imaging modalities have revolutionized the approach to diagnosis of these diseases. Specifically, color Doppler ultrasound, computed tomography and angiography, magnetic resonance imaging, positron emission tomography, or invasive catheterization as indicated have become fundamental in the work up of any patient with suspected systemic or localized vasculitis. This review presents the key diagnostic imaging modalities and their clinical utility in the evaluation of systemic vasculitis.
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Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and, with new innovative methods, can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the Genomics Research to Elucidate the Genetics of Rare Diseases consortium and analyzed using the seqr platform. The addition of CNV detection to exome analysis identified causal CNVs for 171 families (2.6%). The estimated sizes of CNVs ranged from 293 bp to 80 Mb. The causal CNVs consisted of 140 deletions, 15 duplications, 3 suspected complex structural variants (SVs), 3 insertions, and 10 complex SVs, the latter two groups being identified by orthogonal confirmation methods. To classify CNV variant pathogenicity, we used the 2020 American College of Medical Genetics and Genomics/ClinGen CNV interpretation standards and developed additional criteria to evaluate allelic and functional data as well as variants on the X chromosome to further advance the framework. We interpreted 151 CNVs as likely pathogenic/pathogenic and 20 CNVs as high-interest variants of uncertain significance. Calling CNVs from existing exome data increases the diagnostic yield for individuals undiagnosed after standard testing approaches, providing a higher-resolution alternative to arrays at a fraction of the cost of genome sequencing. Our improvements to the classification approach advances the systematic framework to assess the pathogenicity of CNVs.
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Variaciones en el Número de Copia de ADN , Secuenciación del Exoma , Exoma , Enfermedades Raras , Humanos , Variaciones en el Número de Copia de ADN/genética , Enfermedades Raras/genética , Enfermedades Raras/diagnóstico , Exoma/genética , Masculino , Femenino , Estudios de Cohortes , Pruebas Genéticas/métodosRESUMEN
BACKGROUND: The current generation of radiolabeled PSMA-targeting therapeutic agents is limited by prominent salivary gland binding, which results in dose-limiting xerostomia from radiation exposure. JB-1498 is a urea-based small molecule with a highly negatively charged linker targeting prostate specific membrane antigen (PSMA). Prior work on a similar tracer with the same negatively charged linker demonstrated low normal organ/soft tissue background uptake compared to [68Ga]Ga-PSMA-11. The purpose of this study was to investigate if [68Ga]Ga-JB-1498 had reduced salivary gland uptake in mice compared to [68Ga]Ga-PSMA-11. RESULTS: JB-1498 demonstrated high affinity for PSMA binding and tumor uptake in a murine tumor model. In an initial biodistribution study with low molar activity, [68Ga]Ga-JB-1498 demonstrated salivary gland uptake of 0.13 ± 0.01%ID/g. In a second biodistribution study in non-tumor-bearing mice with high molar activity, [68Ga]Ga-JB1498 demonstrated salivary gland uptake of 0.39 ± 0.24% ID/g and kidney activity of 10.12 ± 1.73% ID/g at one hour post IV injection. This salivary gland uptake is significantly less than the published uptake of [68Ga]Ga-PSMA-11. Micro-PET visually confirmed the findings of the biodistribution studies. Dynamic micro-PET imaging demonstrated gradually decreasing [68Ga]Ga-JB1498 activity in salivary glands and kidneys, compared to gradually increasing [68Ga]Ga-PSMA-11 activity in these two organs during the first hour. CONCLUSION: Biodistribution and micro-PET imaging of [68Ga]Ga-JB-1498 demonstrate significantly decreased salivary gland uptake and different pharmacokinetic behavior in kidneys and salivary glands in mice compared to [68Ga]Ga-PSMA-11. Our findings suggest that constructing a PSMA-targeting molecule with a highly negatively charged linker is a promising strategy to reduce salivary gland uptake of GCP-II/PSMA ligands in theranostic applications.
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Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and with new innovative methods can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the GREGoR consortium. Each family's CNV data was analyzed using the seqr platform and candidate CNVs classified using the 2020 ACMG/ClinGen CNV interpretation standards. We developed additional evidence criteria to address situations not covered by the current standards. The addition of CNV calling to exome analysis identified causal CNVs for 173 families (2.6%). The estimated sizes of CNVs ranged from 293 bp to 80 Mb with estimates that 44% would not have been detected by standard chromosomal microarrays. The causal CNVs consisted of 141 deletions, 15 duplications, 4 suspected complex structural variants (SVs), 3 insertions and 10 complex SVs, the latter two groups being identified by orthogonal validation methods. We interpreted 153 CNVs as likely pathogenic/pathogenic and 20 CNVs as high interest variants of uncertain significance. Calling CNVs from existing exome data increases the diagnostic yield for individuals undiagnosed after standard testing approaches, providing a higher resolution alternative to arrays at a fraction of the cost of genome sequencing. Our improvements to the classification approach advances the systematic framework to assess the pathogenicity of CNVs.
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Antígenos de Superficie , Glutamato Carboxipeptidasa II , Glándulas Salivales , Humanos , Ligandos , RadiofármacosRESUMEN
PURPOSE: Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions. METHODS: Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation. RESULTS: Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUVmax statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUVmean (AUC = 0.875; p = 0.018), SUVpeak (AUC = 0.813; p = 0.007), and SUVpeak-to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUVmax-to-normal-brain (p = 0.1) and SUVmean-to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2). CONCLUSIONS: In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance.
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Neoplasias Encefálicas , Radiocirugia , Adulto , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiocirugia/efectos adversos , Proyectos Piloto , Estudios Prospectivos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/etiología , Necrosis/diagnóstico por imagen , Necrosis/etiologíaRESUMEN
ABSTRACT: CT pulmonary angiogram and ventilation-perfusion scintigraphy are the 2 primary imaging modalities for evaluating patients with CTEPH (chronic thromboembolic pulmonary hypertension). PET/CT and MRI currently have a limited role in the evaluation of acute or chronic pulmonary embolism. We present incidentally captured dynamic pulmonary perfusion images in a patient with history of CTEPH who underwent 82 Rb myocardial perfusion PET/CT for evaluation of chest pain. Analysis of the PET data revealed delayed perfusion of the affected lobes suggesting collateralization, highlighting a potentially new imaging paradigm for assessment of pulmonary perfusion.
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Hipertensión Pulmonar , Embolia Pulmonar , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pulmón , Tomografía de Emisión de Positrones , Enfermedad CrónicaRESUMEN
BACKGROUND AND AIMS: Radiolabeled short peptide ligands targeting prostate-specific membrane antigen (PSMA) were developed initially for imaging and treatment of prostate cancers. While many nonprostate solid tumors including hepatocellular carcinoma (HCC) express little PSMA, their neovasculature expresses a high level of PSMA, which is avid for Gallium-68-labeled PSMA-targeting radio-ligand (68Ga-PSMA-11) for positron emission tomography (PET). However, the lack of a spontaneous animal model of tumor-associated vascular PSMA overexpression has hindered the development and assessment of PSMA-targeting radioligands for imaging and therapy of the nonprostatic cancers. We identified detectable indigenous PSMA expression on tumor neovascular endothelia in a naturally occurring woodchuck model of HCC. METHODS: Molecular docking was performed with 3 bait PSMA ligands and compared between human and woodchuck PSMA. Initially, PET images were acquired dynamically after intravenously injecting 37 MBq (1.0 mCi) of 68Ga-PSMA-11 into woodchuck models of HCC. Subsequently, 10-minute static PET scans were conducted for other animals 1-hour after injection due to HCC and liver background uptake stabilization at 30-45 minutes after injection. Liver tissue samples were harvested after imaging, fresh-frozen for quantitative reverse transcription polymerase chain reaction and western blot for validation, or fixed for histology for correlation. RESULTS: Our preclinical studies confirmed the initial clinical findings of 68Ga-PSMA-11 uptake in HCC. The agents (ligands and antibodies) developed against human PSMA were found to be reactive against the woodchuck PSMA. CONCLUSION: This animal model offers a unique opportunity for investigating the biogenesis of tumor-associated vascular PSMA, its functional role(s), and potentials for future treatment strategies targeting tumor vascular PSMA using already developed PSMA-targeting agents.
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BACKGROUND: There is no consensus on the method of obtaining abdominal aortic aneurysm (AAA) maximum diameters based on computed tomographic angiography, and the reproducibility and accuracy of different methods have recently been debated due to advancements in imaging. This study compared the two most common methods based on orthogonal planes and centerline of flow to determine the discordances and accuracy amongst experiences readers. METHODS: The computed tomographic angiography max diameters of 148 AAAs were measured by three experienced observers, including a vascular surgeon, a radiologist and an imaging cardiologist. Observers used two different methods with standardized protocols: multiplanar reformations based on orthogonal planes, and a software using 3D aortic reconstructions to create centerline flow lumen providing diameters based on cross sections perpendicular to this lumen. Agreements and reliability of measurement methods were assessed by intra-class correlation coefficient and Bland - Altman analysis. Discordances between measurements of the methods and the original reported measurement, as well as outside hospitals were compared. RESULTS: The average age of the cohort was 75 years and aortic diameters ranged from 3.8 to 9.6 cm. For orthogonal readings, there were agreements within 3 mm between 86% and 92% of the time, while centerline - reading agreement was between 88% and 94%, which was not statistically significant. The intra-class correlation coefficient was high between method type and between readers. Within methods, agreement was between 0.96 and 0.97, while within - reader agreement measures was between 0.96 and 0.98. In comparison to the original and the outside hospital reports, 10% ≥ of the original and 20% ≥ of the outside hospital reported measurements were discordant between the readers. CONCLUSION: Maximal AAA measurements can have substantial variability leading to clinical significance and change in patient management and outcomes. Based on the results, orthogonal and centerline measurement methods have equally high agreements and concordance within 3 mm and low variations at a high volume center. However, when compared to the official read reports, there is high discordance rates that can significantly alter patient outcomes. A standardized method of measurement maximum diameter can reduce variations and discordances among different methods.
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Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aortografía/normas , Angiografía por Tomografía Computarizada/normas , Anciano , Anciano de 80 o más Años , Dilatación Patológica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
PURPOSE: We did a comparative analysis of matched and mismatched defects in pre- and post-operative V/Q scans in CTEPH patients. We correlated the number of these defects with pre-operative clinical and hemodynamic parameters. METHODS: This was a retrospective study on 27 patients with CTEPH who underwent surgery. Pre- and post-operative V/Q scans were graded for each lung segment as normal, matched or mismatched defect. Additional pre- and post-operative clinical and hemodynamic parameters that were collected include New York Heart Association functional class, six-minute walk distance in feet, N-terminal pro b-type natriuretic peptide, forced expiratory volume in one second/forced vital capacity, diffusing capacity of the lung for carbon monoxide, pulmonary arterial pressure (systolic, diastolic and mean), right atrial pressure, cardiac output and cardiac index. Pulmonary vascular resistance was then calculated. RESULTS: On a segmental basis, 176 mismatched defects were noted in 27 patients, of which 111 improved post-surgery (63%). 22 of the 34 matched defects improved following surgery (64%). 31 new mismatched defects were observed. The number of pre-operative matched defects per patient ranged from 0 to 6. No statistically significant associations were observed between the number of pre-operative matched defects and pre-operative clinical parameters. No statistically significant associations were observed between the number of improved matched defects and the change in clinical parameters (pre- to post-surgery). CONCLUSION: Both matched and mismatched defects on preoperative V/Q scans can show normalization post-surgery. The extent of matched defects on a preoperative V/Q scan does not correlate significantly with other clinical and hemodynamic parameters.
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Hipertensión Pulmonar/diagnóstico por imagen , Gammagrafía de Ventilacion-Perfusión , Enfermedad Crónica , Femenino , Humanos , Hipertensión Pulmonar/fisiopatología , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Embolia Pulmonar , Estudios RetrospectivosRESUMEN
OBJECTIVES: The aim of this study was to compare the morphology, immune phenotype, and cytokine profiles between myocardial telocytes (TCs) and bone marrow mesenchymal stem cells (MSCs), and explore the difference between those two types of interstitial cells. METHODS: TCs and MSCs were cultured in vitro and cell morphology was observed with a light microscope. The expression levels of CD34, c-kit, and vimentin were detected by immunofluorescence, RT-qPCR, and Western blotting in both TCs and MSCs. The related supernatant was collected and total of 49 cytokine profiles were detected by RayBio Mice Cytokine Antibody Array. Significantly different cytokines were further confirmed by ELISA. RESULTS: TCs have small cellular body and very long prolongations and they were CD34+/c-kit+/vimentin+, whereas MSCs have no telopodes and they were CD34-/c-kit- /vimentin+. Cytokine profile analysis and ELISA showed that 19 of 49 cytokines were increased dramatically in the supernatant of TCs compared with those of MSCs. Moreover, 9 of 19 cytokines were increased 2-fold at least in the supernatant of TCs compared with those of MSCs. Of 49 cytokines, 30 exhibited no significant changes in the supernatant of TCs compared with those of MSCs. CONCLUSIONS: Using various technologies, we identified that myocardial TCs and MSCs are significantly different in terms of cell structure and cytokine profiles.
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Células Madre Mesenquimatosas/citología , Miocardio/citología , Telocitos/citología , Animales , Antígenos CD34/análisis , Células Cultivadas , Citocinas/análisis , Células Madre Mesenquimatosas/química , Ratones Endogámicos BALB C , Miocardio/química , Proteínas Proto-Oncogénicas c-kit/análisis , Telocitos/química , Vimentina/análisisRESUMEN
In this review, we cover the evolution of knowledge on the biology of prostate-specific membrane antigen (PSMA) and its translation to therapy. The usual key to discovery is a realistic model for experimentation and for testing a hypothesis. A realistic model is especially needed in the case of the human prostate, which differs significantly from the prostate of species often used as research models. We will emphasize the genetic characterization of PSMA, the nature of the PSMA protein, and its role as a carboxypeptidase, with differing important substrates and products in different tissues. We give special prominence to the importance of PSMA as a target for imaging and therapy in prostate cancer and its underdeveloped role for imaging and targeting the neovasculature of tumors other than prostate cancer. Lastly, we bring attention to its importance in other nonprostatic tissues.
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Diagnóstico por Imagen/métodos , Glutamato Carboxipeptidasa II/metabolismo , Radioterapia/métodos , Ácido Fólico/metabolismo , Humanos , Masculino , Terapia Molecular Dirigida , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismoRESUMEN
Radiopaque resorbable inferior vena cava filter (IVCF) were developed to offer a less expensive alternative to assessing filter integrity in preventing pulmonary embolism for the recommended prophylactic period and then simply vanishes without intervention. In this study, we determined the efficacy of gold nanoparticle (AuNP)-infused poly-p-dioxanone (PPDO) as an IVCF in a swine model. Infusion into PPDO loaded 1.14±0.08 % AuNP by weight as determined by elemental analysis. The infusion did not alter PPDO's mechanical strength nor crystallinity (Kruskal-Wallis one-way ANOVA, p<0.05). There was no cytotoxicity observed (one-way ANOVA, p<0.05) when tested against RF24 and MRC5 cells. Gold content in PPDO was maintained at ~2000 ppm during the 6-week incubation in PBS at 37°C. As a proof-of-concept, two pigs were deployed with IVCF, one with AuNP-PPDO and the other without coating. Results show that the stent ring of AuNP-PPDO was highly visible even in the presence of iodine-based contrast agent and after clot introduction, but not of the uncoated IVCF. Autopsy at two weeks post-implantation showed AuNP-PPDO filter was endothelialized onto the IVC wall, and no sign of filter migration was observed. The induced clot was also still trapped within the AuNP-PPDO IVCF. As a conclusion, we successfully fabricated AuNP-infused PPDO IVCF that is radiopaque, has robust mechanical strength, biocompatible, and can be imaged effectively in vivo. This suggests the efficacy of this novel, radiopaque, absorbable IVCF for monitoring its position and integrity over time, thus increasing the safety and efficacy of deep vein thrombosis treatment.
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Imagen por Resonancia Magnética , Pericarditis/diagnóstico por imagen , Tomografía de Emisión de Positrones , Anciano , Neoplasias de la Mama/terapia , Quimioterapia Adyuvante , Dolor en el Pecho/etiología , Edema Cardíaco/diagnóstico por imagen , Femenino , Fluorodesoxiglucosa F18 , Estudios de Seguimiento , Humanos , Aumento de la Imagen , Mediadores de Inflamación/sangre , Mastectomía , Complicaciones Posoperatorias/diagnóstico por imagenRESUMEN
Prostate Specific Membrane Antigen (PSMA) is strongly expressed in prostate cancer. Recently a number of low-molecular-weight inhibitors have demonstrated excellent PSMA targeting activity for both imaging as well as Lutecium-177 radiotherapy in human trials. The paper by Choy et al raises the question of whether we can further increase the effectiveness of PSMA targeted therapy by adding an albumin-binding entity to low-molecular-weight agents.
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Glutamato Carboxipeptidasa II , Neoplasias de la Próstata , Albúminas , Amidas , Animales , Antígenos de Superficie , Humanos , Ligandos , Masculino , Ratones , Peso Molecular , Ácidos Fosfóricos , Distribución TisularRESUMEN
Targeted nanomedicines offer a strategy for greatly enhancing accumulation of a therapeutic within a specific tissue in animals. In this study, we report on the comparative targeting efficiency toward prostate-specific membrane antigen (PSMA) of a number of different ligands that are covalently attached by the same chemistry to a polymeric nanocarrier. The targeting ligands included a small molecule (glutamate urea), a peptide ligand, and a monoclonal antibody (J591). A hyperbranched polymer (HBP) was utilized as the nanocarrier and contained a fluorophore for tracking/analysis, whereas the pendant functional chain-ends provided a handle for ligand conjugation. Targeting efficiency of each ligand was assessed in vitro using flow cytometry and confocal microscopy to compare degree of binding and internalization of the HBPs by human prostate cancer (PCa) cell lines with different PSMA expression status (PC3-PIP (PSMA+) and PC3-FLU (PSMA-). The peptide ligand was further investigated in vivo, in which BALB/c nude mice bearing subcutaneous PC3-PIP and PC3-FLU PCa tumors were injected intravenously with the HBP-peptide conjugate and assessed by fluorescence imaging. Enhanced accumulation in the tumor tissue of PC3-PIP compared to PC3-FLU highlighted the applicability of this system as a future imaging and therapeutic delivery vehicle.
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Antígenos de Superficie/efectos de los fármacos , Glutamato Carboxipeptidasa II/efectos de los fármacos , Nanomedicina , Polímeros/química , Espectroscopía de Resonancia Magnética con Carbono-13 , Línea Celular Tumoral , Humanos , Ligandos , Masculino , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
In just over a decade, hybrid imaging with FDG PET/CT has become a standard bearer in the management of cancer patients. An exquisitely sensitive whole-body imaging modality, it combines the ability to detect subtle biologic changes with FDG PET and the anatomic information offered by CT scans. With advances in MR technology and advent of novel targeted PET radiotracers, hybrid PET/MRI is an evolutionary technique that is poised to revolutionize hybrid imaging. It offers unparalleled spatial resolution and functional multi-parametric data combined with biologic information in the non-invasive detection and characterization of diseases, without the deleterious effects of ionizing radiation. This article reviews the basic principles of FDG PET and MR imaging, discusses the salient technical developments of hybrid PET/MR systems, and provides an introduction to FDG PET/MR image acquisition.
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Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Imagen Multimodal/métodos , Neoplasias/patología , Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Humanos , Física , Radiofármacos , Imagen de Cuerpo Entero/métodosRESUMEN
Traditionally, hydrogen sulfide (H2S) was simply considered as a toxic and foul smelling gas, but recently H2S been brought into the spot light of cardiovascular research and development. Since the 1990s, H2S has been mounting evidence of physiological properties such as immune modification, vascular relaxation, attenuation of oxidative stress, inflammatory mitigation, and angiogenesis. H2S has since been recognized as the third physiological gaseous signaling molecule, along with CO and NO [65,66]. H2S is produced endogenously through several key enzymes, including cystathionine ß-lyase (CBE), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST)/cysteine aminotransferase (CAT). These specific enzymes are expressed accordingly in various organ systems and CSE is the predominant H2S-producing enzyme in the cardiovascular system. The cystathionine γ-lyase (CSE)/H2S pathway has demonstrated various cardioprotective effects, including anti-atherosclerosis, anti-hypertension, pro-angiogenesis, and attenuation of myocardial ischemia-reperfusion injury. CSE exhibits its anti-atherosclerotic effect through 3 mechanisms, namely reduction of chemotactic factor inter cellular adhesion molecule-1 (ICAM-1) and CX3CR1, inhibition of macrophage lipid uptake, and induction of smooth muscle cell apoptosis via MAPK pathway. The CSE/H2S pathway's anti-hypertensive properties are demonstrated via aortic vasodilation through several mechanisms, including the direct stimulation of KATP channels of vascular smooth muscle cells (VSMCs), induction of MAPK pathway, and reduction of homocysteine buildup. Also, CSE/H2S pathway plays an important role in angiogenesis, particularly in increased endothelial cell growth and migration, and in increased vascular network length. In myocardial ischemia-reperfusion injuries, CSE/H2S pathway has shown a clear cardioprotective effect by preserving mitochondria function, increasing antioxidant production, and decreasing infarction injury size. However, CSE/H2S pathway's role in inflammation mitigation is still clouded, due to both pro and anti-inflammatory results presented in the literature, depending on the concentration and form of H2S used in specific experiment models.