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1.
G Ital Cardiol (Rome) ; 25(9): 690-692, 2024 Sep.
Artigo em Italiano | MEDLINE | ID: mdl-39239821

RESUMO

Although mitral annular calcification is a common degenerative condition of the fibrous mitral annulus, tricuspid annular calcification, especially isolated, is rare. We report the case of a 73-year-old male, with a history of hypertension and severe kyphoscoliosis, referred to the emergency department for progressive dyspnea and leg swelling. Echocardiography revealed a dilated right heart with a homogeneous, hyperechoic, crescent shaped mass along the tricuspid annulus. Computed tomography confirmed the calcific nature of the lesion. Right heart catheterization revealed mild pre-capillary pulmonary hypertension and a mild spirometrically-defined restrictive ventilatory defect. Kyphoscoliosis has recently been associated with alterations in cardiac deformation and with an increased risk of restrictive lung disease. In our patient, we hypothesized that both these anomalies could have led to premature tricuspid annular degeneration resulting in a giant tricuspid calcification.


Assuntos
Calcinose , Cifose , Escoliose , Valva Tricúspide , Humanos , Masculino , Idoso , Calcinose/complicações , Calcinose/diagnóstico por imagem , Valva Tricúspide/diagnóstico por imagem , Cifose/complicações , Escoliose/complicações , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ecocardiografia
2.
Am J Case Rep ; 25: e943908, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39223781

RESUMO

BACKGROUND Cardiac calcified amorphous tumor (CCAT), a peculiar and uncommon non-neoplastic cardiac lesion, was initially characterized by Reynolds and colleagues in the medical literature in 1997. This distinctive entity is hallmarked by its unique feature of pedunculated and diffused calcifications, primarily infiltrating the cardiac structures, with a predilection for the mitral valve annulus initially, followed in sequence by the right atrium, right ventricle, left atrium, left ventricle, and tricuspid valve annulus. The nature of CCATs, despite being benign, poses diagnostic dilemmas, as they frequently masquerade as malignant tumors due to their clinical presentations, which resemble those caused by potential complications such as obstructive masses and thromboembolic events. CASE REPORT A 50-year-old man presented to our hospital with shortness of breath. He had been short of breath for more than 5 years after repeated activities. Transthoracic echocardiography showed a mobile high echogenic mass from the middle of the right ventricular wall and pericardial effusion and right heart insufficiency. The electrocardiogram (ECG) results demonstrated a sinus rhythm, complete right bundle branch block, and T-wave alterations. Additionally, the chest computed tomography (CT) scan revealed a slightly enlarged heart with a lack of density and calcification in the right ventricle. He had an uneventful postoperative recovery after the resection of the cardiac tumor. The mass had not continued to grow when we compared it with preoperative cardiac color doppler echocardiography, after 3 months follow-up. CONCLUSIONS CCAT is a rare non-neoplastic cardiac entity. Diagnosis of CCAT poses a challenge due to the absence of distinct clinical features and its frequent misidentification as a malignant tumor mimic. Surgical resection serves as the sole treatment for symptom relief.


Assuntos
Calcinose , Neoplasias Cardíacas , Ventrículos do Coração , Humanos , Masculino , Pessoa de Meia-Idade , Calcinose/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Diagnóstico Diferencial , Ecocardiografia , Tomografia Computadorizada por Raios X
3.
Exp Clin Transplant ; 22(7): 568-571, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39223815

RESUMO

Successful kidney transplant corrects mineral and bone disorderto a large extent; however, disorders can persistin up to 80% ofrecipients.We describe a case of persistent hyperparathyroidism with graft dysfunction and metastatic calcification in graft biopsy. A 48-yearold renal transplant recipient developed graft dysfunction 3 weeks after kidney transplant. During pretransplant workup, the recipient was found to have severe secondary hyperparathyroidism (intact parathyroid hormone level of 2000 pg/mL), which was managed and well controlled before transplant. Graft dysfunction was evaluated using algorithmic approach. Prerenal causes, tacrolimus toxicity, and infections were ruled out. Graft biopsy revealed several foci of tubular and parenchyma calcific deposits (microcalcinosis) with tubular injury. The patient was restarted on medical management of hyperparathyroidism, and he showed improvement over 6 weeks, along with creatinine level returning to nadir value. Vascular and graft calcification is an independent predictor of long-term graftfunction and overall mortality. This report describes the challenges that we faced in diagnosis and management of persistent hyperparathyroidism, as no randomized controlled trials and guidelines are available.


Assuntos
Calcinose , Hiperparatireoidismo Secundário , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/diagnóstico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Biópsia , Calcinose/etiologia , Calcinose/cirurgia , Calcinose/diagnóstico , Aloenxertos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Biomarcadores/sangue , Fatores de Tempo , Nefropatias/etiologia , Nefropatias/diagnóstico , Hormônio Paratireóideo
4.
Artigo em Inglês | MEDLINE | ID: mdl-39240773

RESUMO

Tumoral calcinosis is a rare disorder defined as the development of periarticular calcified masses, typically surrounding large joints, although they may occur in the foot. We present a case of a patient with systemic tumoral calcinosis with lesions in both shoulders and wrists and a relatively large lesion in the right foot presenting with foot pain.


Assuntos
Calcinose , Humanos , Calcinose/diagnóstico por imagem , Calcinose/complicações , Calcinose/diagnóstico , Feminino , Doenças do Pé/diagnóstico , Doenças do Pé/diagnóstico por imagem , Doenças do Pé/cirurgia , Diagnóstico Diferencial , Tomografia Computadorizada por Raios X , Masculino
5.
Artigo em Inglês | MEDLINE | ID: mdl-39240770

RESUMO

Calcified tissue exposed in a leg ulcer can become infected and develop into a nidus of infection leading to sepsis. This case details a patient with a leg wound secondary to skin biopsy. This leg ulceration did not heal due to an underlying calcified mass and led to five hospital admissions for sepsis. She was diagnosed as having calcinosis cutis, which was suspected to be the source of her infections. The calcified mass was resected, and she healed uneventfully without further infections. Calcified soft-tissue masses should be considered in nonhealing leg ulcers and ulcers with multiple recurrent infections. Radiographs can be used to diagnose this condition, and surgical excision can be considered in cases of infection.


Assuntos
Calcinose , Úlcera da Perna , Osteomielite , Humanos , Calcinose/diagnóstico , Calcinose/diagnóstico por imagem , Feminino , Diagnóstico Diferencial , Osteomielite/diagnóstico , Úlcera da Perna/diagnóstico , Úlcera da Perna/etiologia , Dermatopatias/diagnóstico , Calcinose Cutânea
7.
Folia Med (Plovdiv) ; 66(4): 574-577, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39257260

RESUMO

Scrotoliths, or "scrotal pearls," are calcified fibrous loose bodies found within the tunica vaginalis, often seen during radiological evaluation or autopsies. Chronic inflammation due to trauma, parasitic infestations, and torsion and subsequent detachment of the appendices of the testis or epididymis are postulated mechanisms suggested for their formation. They are benign but can mimic a tumor. Scrotoliths can be diagnosed with high-resolution ultrasonography. Here, we report a case in which, during routine dissection, two scrotoliths were found within the tunica vaginalis of the left testis in an elderly male cadaver. Histologically, the central portion of the scrotoliths exhibited concentric collagen lamellae that enclosed calcified remains of tissue debris. There were no arterioles, venules, or microfilarial larvae seen within them. Awareness about the histological findings can help understand the mechanism that led to their formation.


Assuntos
Cadáver , Testículo , Humanos , Masculino , Testículo/patologia , Testículo/diagnóstico por imagem , Doenças Testiculares/patologia , Doenças Testiculares/diagnóstico por imagem , Idoso de 80 Anos ou mais , Escroto/diagnóstico por imagem , Escroto/patologia , Idoso , Calcinose/patologia , Calcinose/diagnóstico por imagem
8.
J Am Coll Cardiol ; 84(12): 1064-1075, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39260927

RESUMO

BACKGROUND: Medical therapy for aortic stenosis (AS) remains an elusive goal. OBJECTIVES: This study sought to establish whether evogliptin, a dipeptidyl peptidase-4 inhibitor, could reduce AS progression. METHODS: A total of 228 patients (age 67 ± 11 years; 33% women) with AS were randomly assigned to receive placebo (n = 75), evogliptin 5 mg (n = 77), or evogliptin 10 mg (n = 76). The primary endpoint was the 96-week change in aortic valve calcium volume (AVCV) on computed tomography. Secondary endpoints included the 48-week change in active calcification volume measured using 18F-sodium fluoride positron emission tomography (18F-NaF PET). RESULTS: There were no significant differences in the 96-week changes in AVCV between evogliptin 5 mg and placebo (-5.27; 95% CI: -55.36 to 44.82; P = 0.84) or evogliptin 10 mg and placebo (-18.83; 95% CI: -32.43 to 70.10; P = 0.47). In the placebo group, the increase in AVCV between 48 weeks and 96 weeks was higher than that between baseline and 48 weeks (136 mm3; 95% CI: 108-163 vs 102 mm3; 95% CI: 75-129; P = 0.0485). This increasing trend in the second half of the study was suppressed in both evogliptin groups. The 48-week change in active calcification volume on 18F-NaF PET was significantly lower in both the evogliptin 5 mg (-1,325.6; 95% CI: -2,285.9 to -365.4; P = 0.008) and 10-mg groups (-1,582.2; 95% CI: -2,610.8 to -553.5; P = 0.0038) compared with the placebo group. CONCLUSIONS: This exploratory study did not demonstrate the protective effect of evogliptin on AV calcification. Favorable 18F-NaF PET results and possible suppression of aortic valve calcification with longer medication use in the evogliptin groups suggest the need for larger confirmatory trials. (A Multicenter, Double-blind, Placebo-controlled, Stratified-randomized, Parallel, Therapeutic Exploratory Clinical Study to Evaluate the Efficacy and Safety of DA-1229 in Patients With Calcific Aortic Valve Disease; NCT04055883).


Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Calcinose , Progressão da Doença , Humanos , Feminino , Masculino , Idoso , Calcinose/tratamento farmacológico , Calcinose/diagnóstico por imagem , Estenose da Valva Aórtica/tratamento farmacológico , Estenose da Valva Aórtica/diagnóstico por imagem , Pessoa de Meia-Idade , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Método Duplo-Cego , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Resultado do Tratamento , Tomografia Computadorizada por Raios X , Piperazinas
9.
JACC Cardiovasc Interv ; 17(17): 2023-2037, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39260960

RESUMO

BACKGROUND: Research on the role of transcatheter heart valve (THV) deformation and calcium distribution in patients with bicuspid aortic valves (BAVs) undergoing transcatheter aortic valve replacement (TAVR) remains limited. OBJECTIVES: The aim of this study was to evaluate the impact of THV deformation on clinical outcomes in individuals with BAVs undergoing TAVR and the influence of calcium on these outcomes. METHODS: In total, 229 consecutive patients with BAVs who underwent TAVR with balloon-expandable valves and had computed tomography (CT) performed 30 days post-TAVR were analyzed. Patients were stratified into 3 groups: group 1 (n = 125), with no THV underexpansion or eccentricity; group 2 (n = 69), with underexpansion or eccentricity; and group 3 (n = 35), with both. Calcium distribution was assessed using CT, and its associations with clinical outcomes, including all-cause mortality at 3 years and leaflet thrombosis at 30 days, were determined. A subgroup analysis of patients with type 1 BAVs was conducted. RESULTS: Group 3 exhibited higher rates of all-cause mortality than the other groups, along with the highest risk for hypoattenuated leaflet thickening at 30 days. Multivariate analysis identified annular and left ventricular outflow tract calcification as independent predictors of all-cause mortality and hypoattenuated leaflet thickening. In patients with type 1 BAVs, excessive calcification at the raphe and opposite leaflet were associated with all-cause mortality at 3 years. CONCLUSIONS: THV deformation post-TAVR was significantly linked to all-cause mortality in patients with BAVs. Annular and left ventricular outflow tract calcification correlated with increased risks for all-cause mortality and leaflet thrombosis. (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Thrombosis and Its Treatment With Anticoagulation [RESOLVE]; NCT02318342).


Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Valvuloplastia com Balão , Doença da Válvula Aórtica Bicúspide , Calcinose , Doenças das Valvas Cardíacas , Próteses Valvulares Cardíacas , Desenho de Prótese , Substituição da Valva Aórtica Transcateter , Humanos , Masculino , Feminino , Doença da Válvula Aórtica Bicúspide/diagnóstico por imagem , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/mortalidade , Substituição da Valva Aórtica Transcateter/instrumentação , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Valva Aórtica/fisiopatologia , Valva Aórtica/anormalidades , Resultado do Tratamento , Fatores de Risco , Fatores de Tempo , Calcinose/diagnóstico por imagem , Calcinose/fisiopatologia , Calcinose/mortalidade , Valvuloplastia com Balão/efeitos adversos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/mortalidade , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/fisiopatologia , Doenças das Valvas Cardíacas/cirurgia , Doenças das Valvas Cardíacas/mortalidade , Estudos Retrospectivos , Medição de Risco , Trombose/diagnóstico por imagem , Trombose/etiologia , Tomografia Computadorizada Multidetectores , Valor Preditivo dos Testes
12.
Clin Neurol Neurosurg ; 245: 108517, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39173493

RESUMO

We present the case of a patient with leukoencephalopathy with calcifications and cysts (LCC), who experienced progressive severe hemiparesis despite multiple neurosurgical interventions of a large contralateral cyst. Bevacizumab was proposed as an ultimate treatment option based on prior case reports. While awaiting reimbursement approval for bevacizumab, major improvement occurred in both clinical and radiological disease manifestations. The disease course of LCC is variable and unpredictable; neurosurgical treatment should be reserved for severe and progressive neurological deficits. Bevacizumab has been reported as a promising alternative treatment option. Importantly, in our case the observed clinical improvement would have been attributed to the effects of bevacizumab, if started when requested. Our case underscores the need for a natural history study for LCC and the necessity of validating treatment efficacy by systematic evaluation through appropriate clinical trials rather than relying on anecdotal evidence from published case reports.


Assuntos
Calcinose , Leucoencefalopatias , Humanos , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/complicações , Leucoencefalopatias/tratamento farmacológico , Calcinose/diagnóstico por imagem , Calcinose/tratamento farmacológico , Calcinose/cirurgia , Calcinose/complicações , Cistos/cirurgia , Cistos/complicações , Cistos/diagnóstico por imagem , Masculino , Bevacizumab/uso terapêutico , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética , Feminino , Cistos do Sistema Nervoso Central/cirurgia , Cistos do Sistema Nervoso Central/complicações , Cistos do Sistema Nervoso Central/diagnóstico por imagem , Cistos do Sistema Nervoso Central/tratamento farmacológico
13.
BMC Musculoskelet Disord ; 25(1): 690, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39217286

RESUMO

BACKGROUND: We report a rare case of posterior cruciate ligament (PCL) calcification, which has only been reported in two case studies on PubMed. CASE PRESENTATION: A 71-year-old man developed left popliteal pain in the morning without any history of trauma and the pain became severe that night. On the following day, he presented to our department. The patient could not flex his left knee at all due to pain and swelling. CT and MRI scans showed calcification behind the PCL with mild osteoarthritic changes and accumulation of synovial fluid in the joint. Synovial fluid analysis did not reveal any crystals. Blood tests at first admission showed inflammation, hyperglycemia, and low blood uric acid levels. Although the patient's knee joint was injected with steroids, his symptoms did not improve. Thus, we performed arthroscopic surgery two days after symptoms had appeared. Intraoperatively, we observed a white, soft tissue in the synovial membrane behind the PCL. Part of this tissue was collected for histological analysis, which revealed sparse fibers with calcium deposits. Immediately after surgery, the patient's symptoms were completely gone. Afterward, the patient remained asymptomatic one month after surgery. CONCLUSION: This is the first reported case of debridement of PCL calcification and ossification that was performed soon after symptoms appeared. In addition, we demonstrated that early debridement led to complete recovery.


Assuntos
Artroscopia , Calcinose , Desbridamento , Ligamento Cruzado Posterior , Humanos , Masculino , Idoso , Calcinose/cirurgia , Calcinose/diagnóstico por imagem , Calcinose/etiologia , Ligamento Cruzado Posterior/cirurgia , Ligamento Cruzado Posterior/lesões , Resultado do Tratamento , Recuperação de Função Fisiológica , Articulação do Joelho/cirurgia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética
14.
Ann Med ; 56(1): 2396076, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39193705

RESUMO

BACKGROUND: As the burden and distribution of calcification within chronic total occlusion (CTO) lesions can be diverse, its effect on CTO recanalization using multiple devices and techniques is debatable. This study investigated the role of calcification in wiring-based intraplaque tracking techniques for CTO recanalization. METHODS: A modified J-CTO score without counting calcification was used to analyze the procedures of 458 consecutive patients who underwent CTO interventions. Failed guidewire crossing and intraplaque tracking were considered procedural failures. Recanalization time details were analyzed for successful procedures. RESULTS: In patients with calcified CTO, the rate of procedural success only significantly declined to be lower than that of noncalcified CTO when the modified J-CTO score was ≥3 (77% vs. 94%, p = 0.008). In 422 patients with successful procedures, the presence of calcification was irrelevant to guidewire crossing time, but was accompanied with longer time from guidewire cross to final angiogram when the modified J-CTO score was 1-2 (53 ± 35 vs. 35 ± 17 [noncalcified] min, p < 0.001). Multivariate analyses showed that calcification was independently associated with procedural failure (odds ratio [OR] = 5.1, 95% confidence interval [CI] = 1.4-18.3) in lesions with modified J-CTO ≥3, and prolonged angioplasty/stenting procedures >60 min (OR = 4.8, 95% CI = 2.2-10.2) in successfully recanalized lesions with modified J-CTO score 1-2. CONCLUSIONS: Using intraplaque guidewire tracking, calcification was unfavorable for very difficult CTO lesions, and caused prolongation of angioplasty time for lesions with moderate complexity. This suggested that the role of calcification in the J-CTO score could be altered when different recanalization techniques were applied for CTO interventions.


Since several commonly used scoring systems for grading the difficulty of CTO-PCI are derived from multiple recanalization techniques and devices, their application should be fundamental. However, most CTO interventionists usually have their own favored recanalization techniques in the real-world. As one of the parameters of J-CTO score, the findings of the study suggest that the interpretation of calcification during CTO-PCI could be altered and should be cautious if different recanalization technique was used.


Assuntos
Oclusão Coronária , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/instrumentação , Calcificação Vascular/diagnóstico por imagem , Angiografia Coronária/métodos , Estudos Retrospectivos , Índice de Gravidade de Doença , Calcinose/diagnóstico por imagem , Doença Crônica , Resultado do Tratamento
15.
Medicine (Baltimore) ; 103(32): e39139, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39121273

RESUMO

Calcinosis cutis is classified into 5 main types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. However, it is occasionally misdiagnosed as a malignancy and its management remains challenging. Therefore, in this study, we report our diagnostic and treatment experiences with patients with calcinosis cutis and suggest strategies for improving patient care. This retrospective study included 7 patients (4 men, 3 women; 44.4 ±â€…32.0 years old) who visited our hospital between March 2013 and December 2022 and were diagnosed with calcinosis cutis through histopathological procedures. The patients underwent complete excision of the mass without a safety margin. Frozen biopsy was not performed during surgery. No significant intraoperative or postoperative complications were noted after the application of various imaging techniques for diagnosis and follow-up. All patients showed complete recovery. Follow-up showed no recurrence or complications in the 6 patients who completed 1 year of follow-up. Radiological tests such as plain radiography, ultrasonography, computed tomography, and magnetic resonance imaging are important for accurate diagnosis and treatment of calcinosis cutis. This approach can ensure precise assessment of preoperative lesions, leading to safe and less invasive patient treatment, recurrence prevention, and complications of calcinosis cutis.


Assuntos
Calcinose , Dermatopatias , Humanos , Calcinose/diagnóstico , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Estudos Retrospectivos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Dermatopatias/diagnóstico , Dermatopatias/patologia , Dermatopatias/cirurgia , Calcinose Cutânea
17.
Biomed Pharmacother ; 178: 117241, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39111082

RESUMO

Calcific aortic valve disease (CAVD) primarily involves osteogenic differentiation in human aortic valve interstitial cells (hVICs). Schisandrol B (SolB), a natural bioactive constituent, has known therapeutic effects on inflammatory and fibrotic disorders. However, its impact on valve calcification has not been reported. We investigated the effect of SolB on osteogenic differentiation of hVICs. Transcriptome sequencing was used to analyze potential molecular pathways affected by SolB treatment. The study also included an in vivo murine model using aortic valve wire injury surgery to observe SolB's effect on valve calcification. SolB inhibited the osteogenic differentiation of hVICs, reversing the increase in calcified nodule formation and osteogenic proteins. In the murine model, SolB significantly decreased the peak velocity of the aortic valve post-injury and reduced valve fibrosis and calcification. Transcriptome sequencing identified the p53 signaling pathway as a key molecular target of SolB, demonstrating its role as a molecular glue in the mouse double minute 2 (MDM2)-p53 interaction, thereby promoting p53 ubiquitination and degradation, which further inhibited p53-related inflammatory and senescence response. These results highlighted therapeutic potential of SolB for CAVD via inhibiting p53 signaling pathway and revealed a new molecular mechanism of SolB which provided a new insight of theraputic mechanism for CAVD.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Calcinose , Ciclo-Octanos , Lignanas , Proteína Supressora de Tumor p53 , Animais , Humanos , Masculino , Camundongos , Valva Aórtica/patologia , Valva Aórtica/efeitos dos fármacos , Valva Aórtica/metabolismo , Estenose da Valva Aórtica/tratamento farmacológico , Estenose da Valva Aórtica/patologia , Calcinose/tratamento farmacológico , Calcinose/patologia , Calcinose/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Ciclo-Octanos/farmacologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/patologia , Inflamação/metabolismo , Lignanas/farmacologia , Camundongos Endogâmicos C57BL , Osteogênese/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo
18.
Mol Med ; 30(1): 117, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39123116

RESUMO

BACKGROUND: Lipid metabolism disorders are associated with degeneration of multiple tissues and organs, but the mechanism of crosstalk between lipid metabolism disorder and intervertebral disc degeneration (IDD) has not been fully elucidated. In this study we aim to investigate the regulatory mechanism of abnormal signal of lipid metabolism disorder on intervertebral disc endplate chondrocyte (EPC) senescence and calcification. METHODS: Human intervertebral disc cartilage endplate tissue, cell model and rat hyperlipemia model were performed in this study. Histology and immunohistochemistry were used to human EPC tissue detection. TMT-labelled quantitative proteomics was used to detect differential proteins, and MRI, micro-CT, safranin green staining and immunofluorescence were performed to observe the morphology and degeneration of rat tail intervertebral discs. Flow cytometry, senescence-associated ß-galactosidase staining, alizarin red staining, alkaline phosphatase staining, DCFH-DA fluorescent probe, and western blot were performed to detect the expression of EPC cell senescence, senescence-associated secretory phenotype, calcification-related proteins and the activation of cell senescence-related signaling pathways. RESULTS: Our study found that the highly expressed oxidized low-density lipoprotein (ox-LDL) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in human degenerative EPC was associated with hyperlipidemia (HLP). TMT-labelled quantitative proteomics revealed enriched pathways such as cell cycle regulation, endochondral bone morphogenesis and inflammation. The rat model revealed that HLP could induce ox-LDL, LOX-1, senescence and calcification markers high expression in EPC. Moreover, we demonstrated that ox-LDL-induced EPCs senescence and calcification were dependent on the LOX-1 receptor, and the ROS/P38-MAPK/NF-κB signaling pathway was implicated in the regulation of senescence induced by ox-LDL/LOX-1 in cell model. CONCLUSIONS: So our study revealed that ox-LDL/LOX-1-induced EPCs senescence and calcification through ROS/P38-MAPK/NF-κB signaling pathway, providing information on understanding the link between lipid metabolism disorders and IDD.


Assuntos
Senescência Celular , Condrócitos , Degeneração do Disco Intervertebral , Metabolismo dos Lipídeos , Lipoproteínas LDL , Receptores Depuradores Classe E , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Lipoproteínas LDL/metabolismo , Animais , Humanos , Receptores Depuradores Classe E/metabolismo , Condrócitos/metabolismo , Condrócitos/patologia , Ratos , Masculino , Calcinose/metabolismo , Calcinose/patologia , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Modelos Animais de Doenças , Feminino , Pessoa de Meia-Idade , Transdução de Sinais , Adulto , Proteômica/métodos , Ratos Sprague-Dawley
19.
Urolithiasis ; 52(1): 122, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39196305

RESUMO

Randall's plaques (RP) serve as anchoring sites for calcium oxalate (CaOx) stones, but the underlying mechanism remains unclear. Renal interstitium with a high-calcium environment is identified as pathogenesis of RP formation where the role of human renal interstitial fibroblasts (hRIFs) was highlighted. Our study aims to elucidate the potential mechanism by which a high-calcium environment drives ectopic calcification of hRIFs to participate in RP formation. Alizarin Red staining demonstrated calcium nodules in hRIFs treated with high-calcium medium. Utilizing transcriptome sequencing, tissue factor pathway inhibitor-2 (TFPI-2) was found to be upregulated in high-calcium-induced hRIFs and RP tissues, and TFPI-2 promoted high-calcium-induced calcification of hRIFs. Subsequently, the downstream regulator of TFPI2 was screened by transcriptome sequencing analysis of hRIFs with TFPI-2 knockdown or overexpressed. Dachsous Cadherin Related 1 (DCHS1) knockdown was identified to suppress the calcification of hRIFs enhanced by TFPI-2. Further investigation revealed that TFPI-2/DCHS1 axis promoted high-calcium-induced calcification of hRIFs via disturbing the balance of ENPP1/ALP activities, but without effect on the canonical osteogenic markers, such as osteopontin (OPN), osteogenic factors runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2). In summary, our study mimicked the high-calcium environment observed in CaOx stone patients with hypercalciuria, and discovered that the high-calcium drove ectopic calcification of hRIFs via a novel TFPI-2-DCHS1-ALP/ENPP1 pathway rather than adaption of osteogenic phenotypes to participate in RP formation.


Assuntos
Calcinose , Fibroblastos , Glicoproteínas , Humanos , Calcinose/patologia , Calcinose/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Glicoproteínas/metabolismo , Glicoproteínas/genética , Cálcio/metabolismo , Rim/patologia , Rim/metabolismo , Fosfatase Alcalina/metabolismo , Cálculos Renais/metabolismo , Cálculos Renais/patologia , Cálculos Renais/etiologia , Cálculos Renais/genética , Células Cultivadas
20.
Stroke ; 55(9): 2305-2314, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39101226

RESUMO

BACKGROUND: Carotid siphon calcification (CSC) serves as a marker of atherosclerosis and therefore may influence the outcome after subarachnoid hemorrhage (aSAH). We aimed to analyze the impact of CSC on neurological outcomes, ischemia, and vasospasm. METHODS: A total of 716 patients with aSAH were treated between December 2004 and June 2016 in our central European tertiary neurovascular care center in Essen, Germany. CSC was recorded using the Woodcock scale (grades 0-3) on a computed tomography scan. Study end points included an unfavorable outcome at 6 months post-aSAH (modified Rankin Scale score ≥4), vasospasm, and early cerebral ischemia (72 hours) and delayed cerebral ischemia (delayed cerebral ischemia; >72 hours) in the follow-up computed tomography scans. The associations were adjusted for patients' baseline characteristics and secondary complications. Finally, within a subgroup analysis, patients with and without daily aspirin intake after endovascular aneurysm occlusion were compared. RESULTS: Increasing grades of CSC were associated with lower rates of vasospasm in the anterior circulation. Severe CSC (grade 3) was independently related to the risk of an unfavorable outcome (adjusted odds ratio [aOR], 4.06 [95% CI, 1.98-8.33]; P<0.001) and early cerebral ischemia (aOR, 1.58 [95% CI, 1.03-2.43]; P=0.035) but not delayed cerebral ischemia (aOR, 1.08 [95% CI, 0.67-1.73]; P=0.763). In the aspirin subgroup analysis, the negative effect of severe CSC on functional outcome remained significant only in aSAH cases without aspirin (aOR, 5.47 [95% CI, 2.38-12.54]; P<0.001). In contrast, there was no association between severe CSC and unfavorable outcomes among individuals with daily aspirin intake (aOR, 0.84 [95% CI, 0.59-4.21]; P=0.603). CONCLUSIONS: Our data suggest CSC as a cerebrovascular risk factor resulting in higher rates of early cerebral ischemia and unfavorable outcomes after aSAH. However, by increasing arterial stiffness, CSC might lower the probability of vasospasm, which could explain the missing link between CSC and delayed cerebral ischemia. Additionally, aspirin intake seems to potentially mitigate the negative impact of CSC on aSAH outcome. Further investigations are needed to confirm the observations from the present study.


Assuntos
Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Humanos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/etiologia , Isquemia Encefálica/diagnóstico por imagem , Adulto , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/complicações , Resultado do Tratamento , Artéria Carótida Interna/diagnóstico por imagem , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/complicações , Procedimentos Endovasculares/métodos , Aspirina/uso terapêutico , Calcinose/diagnóstico por imagem , Estudos Retrospectivos
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