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1.
Curr Issues Mol Biol ; 46(7): 7486-7504, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39057085

RESUMEN

Systemic sclerosis (SSc) is a connective tissue disorder characterized by microvascular injury, extracellular matrix deposition, autoimmunity, inflammation, and fibrosis. The clinical complexity and high heterogeneity of the disease make the discovery of potential therapeutic targets difficult. However, the recent progress in the comprehension of its pathogenesis is encouraging. Growth Arrest-Specific 6 (Gas6) and Tyro3, Axl, and MerTK (TAM) receptors are involved in multiple biological processes, including modulation of the immune response, phagocytosis, apoptosis, fibrosis, inflammation, cancer development, and autoimmune disorders. In the present manuscript, we review the current evidence regarding SSc pathogenesis and the role of the Gas6/TAM system in several human diseases, suggesting its likely contribution in SSc and highlighting areas where further research is necessary to fully comprehend the role of TAM receptors in this condition. Indeed, understanding the involvement of TAM receptors in SSc, which is currently unknown, could provide valuable insights for novel potential therapeutic targets.

2.
Med Sci Monit ; 30: e944462, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38932442

RESUMEN

BACKGROUND Preliminary data suggest an adipogenic role for growth arrest-specific 6 (Gas6), a pleiotropic molecule involved in inflammation, proliferation, and hemostasis through its Tyro3, Axl, and MerTK (TAM) receptors. This study compares Gas6 expression in plasma and visceral and subcutaneous adipose tissue in 42 adults with obesity (body mass index ≥40 kg/m²) and 32 normal-weight controls to elucidate its role in obesity and related metabolic alterations. MATERIAL AND METHODS Using a case-control design, we measured Gas6 levels in plasma via a validated sandwich enzyme-linked immunosorbent assay and in adipose tissues through quantitative polymerase chain reactio with specific probes. Medians and correlations were analyzed using Mann-Whitney and Spearman tests. A general linear model assessed the impact of covariates on the Gas6-anthropometric relationship, with statistical significance determined by P values. RESULTS Plasma Gas6 levels were significantly higher in the obese group than in controls (P=0.0006). While Gas6 mRNA expression did not significantly differ in subcutaneous adipose tissue between groups, it was notably higher in visceral than subcutaneous adipose tissue in controls (P<0.05). A significant correlation was found between plasma Gas6 levels and body mass index (P=0.001). CONCLUSIONS Gas6 plasma levels are elevated in morbid obesity, particularly in visceral adipose tissue, and are linked to altered glucose tolerance in female patients. These findings highlight the role of Gas6 in obesity-related metabolic complications and suggest avenues for further research and potential therapies.


Asunto(s)
Tejido Adiposo , Índice de Masa Corporal , Inflamación , Péptidos y Proteínas de Señalización Intercelular , Obesidad Mórbida , Humanos , Femenino , Masculino , Adulto , Péptidos y Proteínas de Señalización Intercelular/sangre , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Inflamación/sangre , Inflamación/metabolismo , Estudios de Casos y Controles , Persona de Mediana Edad , Tejido Adiposo/metabolismo , Obesidad Mórbida/sangre , Obesidad Mórbida/metabolismo , Grasa Intraabdominal/metabolismo , Grasa Subcutánea/metabolismo , Obesidad/metabolismo , Obesidad/sangre
3.
Curr Issues Mol Biol ; 45(10): 7775-7802, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37886934

RESUMEN

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by significant fibrosis of the skin and internal organs, with the main involvement of the lungs, kidneys, heart, esophagus, and intestines. SSc is also characterized by macro- and microvascular damage with reduced peripheral blood perfusion. Several studies have reported more than 240 pathways and numerous dysregulation proteins, giving insight into how the field of biomarkers in SSc is still extremely complex and evolving. Antinuclear antibodies (ANA) are present in more than 90% of SSc patients, and anti-centromere and anti-topoisomerase I antibodies are considered classic biomarkers with precise clinical features. Recent studies have reported that trans-forming growth factor ß (TGF-ß) plays a central role in the fibrotic process. In addition, interferon regulatory factor 5 (IRF5), interleukin receptor-associated kinase-1 (IRAK-1), connective tissue growth factor (CTGF), transducer and activator of transcription signal 4 (STAT4), pyrin-containing domain 1 (NLRP1), as well as genetic factors, including DRB1 alleles, are implicated in SSc damage. Several interleukins (e.g., IL-1, IL-6, IL-10, IL-17, IL-22, and IL-35) and chemokines (e.g., CCL 2, 5, 23, and CXC 9, 10, 16) are elevated in SSc. While adiponectin and maresin 1 are reduced in patients with SSc, biomarkers are important in research but will be increasingly so in the diagnosis and therapeutic approach to SSc. This review aims to present and highlight the various biomarker molecules, pathways, and receptors involved in the pathology of SSc.

4.
Int J Mol Sci ; 24(8)2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37108262

RESUMEN

Clinical knowledge about SARS-CoV-2 infection mechanisms and COVID-19 pathophysiology have enormously increased during the pandemic. Nevertheless, because of the great heterogeneity of disease manifestations, a precise patient stratification at admission is still difficult, thus rendering a rational allocation of limited medical resources as well as a tailored therapeutic approach challenging. To date, many hematologic biomarkers have been validated to support the early triage of SARS-CoV-2-positive patients and to monitor their disease progression. Among them, some indices have proven to be not only predictive parameters, but also direct or indirect pharmacological targets, thus allowing for a more tailored approach to single-patient symptoms, especially in those with severe progressive disease. While many blood test-derived parameters quickly entered routine clinical practice, other circulating biomarkers have been proposed by several researchers who have investigated their reliability in specific patient cohorts. Despite their usefulness in specific contexts as well as their potential interest as therapeutic targets, such experimental markers have not been implemented in routine clinical practice, mainly due to their higher costs and low availability in general hospital settings. This narrative review will present an overview of the most commonly adopted biomarkers in clinical practice and of the most promising ones emerging from specific population studies. Considering that each of the validated markers reflects a specific aspect of COVID-19 evolution, embedding new highly informative markers into routine clinical testing could help not only in early patient stratification, but also in guiding a timely and tailored method of therapeutic intervention.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Reproducibilidad de los Resultados , Biomarcadores , Hospitalización
5.
Int J Mol Sci ; 24(7)2023 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-37047229

RESUMEN

Post-acute conditions after coronavirus disease 2019 (COVID-19) are quite common, although the underlying pathogenetic mechanisms leading to these conditions are not yet completely understood. In this prospective observational study, we aimed to test the hypothesis that Growth Arrest-Specific 6 (Gas6) and its soluble receptors, Axl (sAxl) and MerTK (sMer), might be implicated. A total of 263 subjects underwent a structured clinical evaluation one year after their hospital discharge for COVID-19, and they consented to donate a blood sample to measure their circulating Gas6, sAxl, and sMer levels. A total of 98 (37.3%) post-COVID-19 subjects complained of at least one residual physical symptom one year after their hospital discharge. Univariate analysis revealed that sAxl was marginally associated with residual symptoms, but at the level of logistic regression analysis, only the diffusing capacity of the lungs for carbon monoxide (DLCO) (OR 0.98, CI 95%: 0.96-0.99; p = 0.007) and the female sex (OR 2.49, CI 95%: 1.45-4.28; p = 0.001) were independently associated with long-lasting symptoms. A total of 69 (26.2%) subjects had hair loss. At the level of univariate analysis, Gas6, sAxl, DLCO, and the female gender were associated with its development. In a logistic regression analysis model, Gas6 (OR 0.96, CI 95%: 0.92-0.99; p = 0.015) and sAxl (OR 0.98, CI 95%; 0.97-1.0; p = 0.014), along with the female sex (OR 6.58, CI 95%: 3.39-12.78; p = 0.0001), were independent predictors of hair loss. Decreased levels of Gas6 and sAxl were associated with a history of hair loss following COVID-19. This was resolved spontaneously in most patients, although 23.7% complained of persistent hair loss one year after hospital discharge.


Asunto(s)
COVID-19 , Proteínas Proto-Oncogénicas , Femenino , Humanos , Tirosina Quinasa c-Mer , COVID-19/complicaciones , Péptidos y Proteínas de Señalización Intercelular , Proteínas Tirosina Quinasas Receptoras
7.
Clin Exp Rheumatol ; 39(5): 938-946, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32940209

RESUMEN

OBJECTIVES: The AQUEOUS (Anti-phospholipid syndrome: a QUEstionnaire for yOUng patientS) study aimed to assess how the diagnosis of primary anti-phospholipid syndrome (PAPS) affects the psychosocial status of young patients. METHODS: Subjects with PAPS aged 18-45 years were invited to compile an ad hoc designed questionnaire and the Short Form-12 to assess quality of life (QoL). RESULTS: Ninety-two patients (83.7% females) were recruited in 10 Italian centres. Vascular and obstetric manifestations were equally represented. Nearly half of the patients perceived the need for psychological support, 89.2% when considering women after pregnancy complications. Social activities and working efficiency were reduced in APS patients, also intimacy was threatened. In all cases, fatigue appeared to be the main determinant. PAPS affected family planning, due to fears of treatment side-effects, disease hereditariness, inability to care for the newborn child. Fertility appeared to be conserved: the median time to pregnancy was 2 months; assisted reproduction techniques were pursued by 5 women. Our survey documented significantly lower rates of hospitalisation and learning disabilities in 51 children born after APS diagnosis as compared to 48 children born before. PAPS patients displayed lower QoL in physical and, to a greater extent, mental scores compared to the general Italian population. Both components were significantly lower in women and in patients with fatigue. CONCLUSIONS: The AQUEOUS study assessed for the first time the unmet needs of young PAPS patients, enabling the development of a future "youth-focused" strategy to reduce disease burden.


Asunto(s)
Síndrome Antifosfolípido , Complicaciones del Embarazo , Adolescente , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/epidemiología , Femenino , Humanos , Recién Nacido , Italia/epidemiología , Masculino , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Calidad de Vida , Encuestas y Cuestionarios
8.
Clin Exp Rheumatol ; 39(1): 132-138, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32573415

RESUMEN

OBJECTIVES: Growth arrest-specific 6 (Gas6) and its receptors have been shown to play a crucial role in the homeostasis of the innate immune system by regulating apoptosis and inflammation. We aimed to verify whether an impairment of this system is associated with systemic lupus erythematosus (SLE) disease activity and with lupus nephritis (LN). METHODS: Plasma Gas6 and the soluble cleaved form of the receptors MerTK (sMer) and Axl (sAxl) concentrations were measured in n=59 SLE patients (n=44 with nephritis, 75%) and analysed in relationship to clinical and laboratory data. RESULTS: Patients with LN were characterised by higher Gas6 (19.0 ng/mL [16.8-24.5] vs. 16.5 ng/mL [13.89-18.91]; p=0.03) and sAxl plasma levels than those without LN (31.36 ng/mL [25.1-41.4] vs. 20.2 ng/mL [15.6-30.7]; p=0.03); conversely sMer plasma concentrations were similar between groups. All the three biomarkers studied were directly correlated to creatinine and daily proteinuria, being inversely related to creatinine clearance. 39 patients had a proteinuria level of <0.5 mg/day, 14 between 0.5 and 3.5 mg/day and 5 had ≥3.5 g/day; Gas6, sAxl and sMer plasma concentrations significantly increased for increasing degree of proteinuria (test for trend p=0.0002; p=0.02; p=0.009, respectively).These correlations were confirmed in multiple linear regression analysis models accounting for gender, age, disease duration and concomitant treatment. CONCLUSIONS: Plasma Gas6, sAxl and sMer concentrations are associated with the severity of LN in patients affected by SLE. The excess cleavage of TAM receptors might contribute to LN pathogenesis.


Asunto(s)
Nefritis Lúpica , Proteínas Tirosina Quinasas Receptoras , Biomarcadores , Humanos , Péptidos y Proteínas de Señalización Intercelular , Nefritis Lúpica/diagnóstico , Plasma , Proteínas Proto-Oncogénicas
9.
J Thromb Thrombolysis ; 52(3): 746-753, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34110529

RESUMEN

Patients with Coronavirus Disease-2019 (COVID-19) have haemostatic dysfunction and are at higher risk of thrombotic complications. Although age is a major risk factor for outcome impairment in COVID-19, its impact on coagulative patterns here is still unclear. We investigated the association of Endogenous Thrombin Potential (ETP) with thrombotic and haemorrhagic events according to different ages in patients admitted for COVID-19. A total of 27 patients with COVID-19-related pneumonia, without need for intensive care unit admission or mechanical ventilation at hospital presentation, and 24 controls with non-COVID-19 pneumonia were prospectively included. ETP levels were measured on admission. Patients were evaluated for major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, stroke, transient ischemic attack, venous thromboembolism) and bleeding complications [according to Bleeding Academic Research Consortium (BARC) definition] during in-hospital stay. COVID-19 patients had similar ETP levels compared to controls (AUC 93 ± 24% vs 99 ± 21%, p = 0.339). In the COVID-19 cohort, patients with in-hospital MACE showed lower ETP levels on admission vs those without (AUC 86 ± 14% vs 95 ± 27%, p = 0.041), whereas ETP values were comparable in patients with or without bleeding (AUC 82 ± 16% vs 95 ± 26%, p = 0.337). An interaction between age and ETP levels for both MACE and bleeding complications was observed, where a younger age was associated with an inverse relationship between ETP values and adverse event risk (pint 0.018 for MACE and 0.050 for bleeding). Patients with COVID-19 have similar thrombin potential on admission compared to those with non-COVID-19 pneumonia. In younger COVID-19 patients, lower ETP levels were associated with a higher risk of both MACE and bleeding.


Asunto(s)
COVID-19/complicaciones , Hemostasis , Hospitalización , Trombina/metabolismo , Trombosis/etiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , COVID-19/sangre , COVID-19/mortalidad , COVID-19/terapia , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Trombosis/sangre , Trombosis/mortalidad , Trombosis/terapia , Factores de Tiempo
10.
J Thromb Thrombolysis ; 52(3): 782-790, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33649979

RESUMEN

A pro-thrombotic milieu and a higher risk of thrombotic events were observed in patients with CoronaVirus disease-19 (COVID-19). Accordingly, recent data suggested a beneficial role of low molecular weight heparin (LMWH), but the optimal dosage of this treatment is unknown. We evaluated the association between prophylactic vs. intermediate-to-fully anticoagulant doses of enoxaparin and in-hospital adverse events in patients with COVID-19. We retrospectively included 436 consecutive patients admitted in three Italian hospitals. Outcome according to the use of prophylactic (4000 IU) vs. higher (> 4000 IU) daily dosage of enoxaparin was evaluated. The primary end-point was in-hospital death. Secondary outcome measures were in-hospital cardiovascular death, venous thromboembolism, new-onset acute respiratory distress syndrome (ARDS) and mechanical ventilation. A total of 287 patients (65.8%) were treated with the prophylactic enoxaparin regimen and 149 (34.2%) with a higher dosing regimen. The use of prophylactic enoxaparin dose was associated with a similar incidence of all-cause mortality (25.4% vs. 26.9% with the higher dose; OR at multivariable analysis, including the propensity score: 0.847, 95% CI 0.400-0.1.792; p = 0.664). In the prophylactic dose group, a significantly lower incidence of cardiovascular death (OR 0.165), venous thromboembolism (OR 0.067), new-onset ARDS (OR 0.454) and mechanical intubation (OR 0.150) was observed. In patients hospitalized for COVID-19, the use of a prophylactic dosage of enoxaparin appears to be associated with similar in-hospital overall mortality compared to higher doses. These findings require confirmation in a randomized, controlled study.


Asunto(s)
Anticoagulantes/administración & dosificación , COVID-19/terapia , Enoxaparina/administración & dosificación , Hospitalización , Tromboembolia/prevención & control , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/mortalidad , Enoxaparina/efectos adversos , Femenino , Mortalidad Hospitalaria , Humanos , Italia , Masculino , Persona de Mediana Edad , Factores Protectores , Respiración Artificial , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Tromboembolia/sangre , Tromboembolia/diagnóstico , Tromboembolia/mortalidad , Factores de Tiempo , Resultado del Tratamiento
12.
Cell Physiol Biochem ; 54(3): 401-416, 2020 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-32330379

RESUMEN

BACKGROUND/AIMS: Oxidative stress and mitochondria dysfunction could be involved in the onset of non-alcoholic fatty liver disease (NAFLD) and in its progression to non-alcoholic steatohepatitis (NASH). Estrogens/phytoestrogens could counteract liver fat deposition with beneficial effects against NAFLD by unclear mechanisms. We aimed to analyze the protective effects elicited by genistein/estradiol in hepatocytes cultured in NAFLD-like medium on cell viability, triglycerides accumulation, mitochondrial function and oxidative stress and the role of NLRP3 inflammasome, toll like receptors 4 (TLR4), Akt and 5' AMP-activated protein kinase (AMPK)α1/2. METHODS: Human primary hepatocytes/hepatoma cell line (Huh7.5 cells) were incubated with a 2 mM mixture of oleate/palmitate in presence/absence of genistein/17ß-estradiol. In some experiments, Huh7.5 cells were exposed to various inhibitors of the above pathways and estrogenic receptors (ERs) and G protein-coupled estrogen receptor (GPER) blockers, before genistein/17ß-estradiol. Cell viability, mitochondrial membrane potential, reactive oxygen species and triglycerides content were examined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT), 5,51,6,61-tetrachloro-1,11,3,31 tetraethylbenzimidazolyl carbocyanine iodide (JC-1), 2,7-dichlorodihydrofluorescein diacetate (H2DCFDA) and the Triglyceride Colorimetric Assay. The expression/activation of kinases was analyzed by means of Western blot. RESULTS: Genistein/17ß-estradiol protected hepatocytes against NAFLD-like medium, by preventing the loss of cell viability and mitochondrial function, triglycerides accumulation and peroxidation. The blocking of kinases, ERs and GPER was able to reduce the above effects, which were potentiated by NLRP3 inflammasome. CONCLUSION: Our findings suggest novel mechanisms underlying the protective effects elicited by phytoestrogens/estrogens against NAFLD/NASH and open novel therapeutic perspectives in the management of NAFLD in postmenopausal women.


Asunto(s)
Supervivencia Celular/efectos de los fármacos , Estradiol/farmacología , Genisteína/farmacología , Hepatocitos/efectos de los fármacos , Inflamasomas/metabolismo , Mitocondrias/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Quinasas de la Proteína-Quinasa Activada por el AMP , Línea Celular , Hepatocitos/metabolismo , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fitoestrógenos/farmacología , Proteínas Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de Estrógenos/antagonistas & inhibidores , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Receptor Toll-Like 4/metabolismo , Triglicéridos/metabolismo
13.
Clin Exp Rheumatol ; 38(2): 343-349, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31573472

RESUMEN

Vitamin D is a pleiotropic molecule with a well-characterised immunomodulatory activity in vitro; however, its potential clinical application in autoimmune conditions has yet to be clarified. Several authors have investigated the use of vitamin D as a disease-modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA), obtaining divergent conclusions. This systematic review summarises and critically analyses the findings of papers assessing the impact of vitamin D supplementation on pain relief, disease activity, functional status and flare rate. We conclude that the correction of hypovitaminosis D may have a beneficial effect on pain perception; moreover, the achievement of an adequate plasma vitamin D concentration obtained with high-dose regimens might evoke immunomodulatory activities of vitamin D and favourably impact on disease control. Nevertheless, the current evidence is still not strong enough to support the use of cholecalciferol as a DMARD in RA, and further studies are required to clarify this issue.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Colecalciferol/uso terapéutico , Deficiencia de Vitamina D , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Colecalciferol/deficiencia , Humanos , Deficiencia de Vitamina D/complicaciones
14.
Respiration ; 99(11): 970-978, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33075793

RESUMEN

BACKGROUND: Bronchoscopy with bronchoalveolar lavage (BAL) during the SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) pandemic should be reserved to a limited number of clinical indications. The yield of BAL for the diagnosis of suspected or confirmed pulmonary SARS-CoV-2 infection is still unknown. OBJECTIVES: We aimed to evaluate the diagnostic ratio of BAL in detecting SARS-CoV-2 pulmonary infection in patients undergoing bronchoscopy for different indications as well as describe the clinical, radiological, and endoscopic characteristics of patients with SARS-CoV-2 on BAL. METHOD: We conducted a multicenter retrospective study including all patients who underwent bronchoscopy for the detection of SARS-CoV-2 on BAL. Clinical, computed tomography (CT), endoscopic, and microbiologic data were gathered from March 16th to May 27th, 2020. RESULTS: 131 patients were included. Bronchoscopy was performed for suspected SARS-CoV-2 infection (65.5%), alternative diagnosis (12.9%), suspected superinfections (19.8%), and lung atelectasis (1.5%). SARS-CoV-2 was isolated on BAL 43 times (32.8%) and the highest isolation rate was in patients with suspected SARS-CoV-2 infection (74.4%); 76% of positive patients had a double-negative nasopharyngeal swab. Peripheral, posterior and multilobar CT opacities were more frequent in SARS-CoV-2 patients, and the number of CT findings was higher in positive patients, particularly those with suspected SARS-CoV-2 infection. We recorded a progressive reduction of SARS-CoV-2 isolation during the observation period. CONCLUSIONS: In our centers, the rate of detection of SARS-CoV-2 on BAL in patients with suspected infection was 37.2%. The agreement of BAL with nasopharyngeal swabs was high; CT alterations could predict the pretest probability of SARS-CoV-2 infection, but suspicion of viral infection should be always considered.


Asunto(s)
Líquido del Lavado Bronquioalveolar/virología , Prueba de Ácido Nucleico para COVID-19 , COVID-19/diagnóstico , SARS-CoV-2/aislamiento & purificación , Anciano , Lavado Broncoalveolar , Broncoscopía , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
15.
Natl Med J India ; 33(6): 344-346, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-34341211

RESUMEN

Multicentric Castleman disease (MCD) is a rare clinical entity characterized by a polyclonal lymphoid proliferation, leading to generalized lymphadenopathy, organomegaly and systemic symptoms. It has been reported in association with either other monoclonal or polyclonal lymphoid disorders, such as POEMS syndrome and immunoglobulin (Ig)G4-related disease. We present a patient showing a variant of MCD, sharing common features with POEMS syndrome and associated with the proliferation of IgG4-producing plasma cells.


Asunto(s)
Enfermedad de Castleman , Trastornos Linfoproliferativos , Enfermedad de Castleman/diagnóstico , Humanos
16.
Int J Mol Sci ; 20(20)2019 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-31614787

RESUMEN

Fibrosis is the result of an overly abundant deposition of extracellular matrix (ECM) due to the fact of repetitive tissue injuries and/or dysregulation of the repair process. Fibrogenesis is a pathogenetic phenomenon which is involved in different chronic human diseases, accounting for a high burden of morbidity and mortality. Despite being triggered by different causative factors, fibrogenesis follows common pathways, the knowledge of which is, however, still unsatisfactory. This represents a significant limit for the development of effective antifibrotic drugs. In the present paper, we aimed to review the current evidence regarding the potential role played in fibrogenesis by growth arrest-specific 6 (Gas6) and its receptors Tyro3 protein tyrosine kinase (Tyro3), Axl receptor tyrosine kinase (Axl), and Mer tyrosine kinase protooncogene (MerTK) (TAM). Moreover, we aimed to review data about the pathogenetic role of this system in the development of different human diseases characterized by fibrosis. Finally, we aimed to explore the potential implications of these findings in diagnosis and treatment.


Asunto(s)
Sistema Cardiovascular/patología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Cirrosis Hepática/metabolismo , Hígado/patología , Pulmón/patología , Tirosina Quinasa c-Mer/metabolismo , Animales , Sistema Cardiovascular/metabolismo , Fibrosis , Humanos , Inflamación , Péptidos y Proteínas de Señalización Intercelular/genética , Hígado/metabolismo , Cirrosis Hepática/genética , Pulmón/metabolismo , Tirosina Quinasa c-Mer/genética
17.
Respir Res ; 19(1): 35, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29490639

RESUMEN

We would like to comment on the article entitled "Prognostic and diagnostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from ACE 2 study" by Jacob A. Winther and colleagues, in the light of the results of a multicentric study published in 2014 by Vetrone F. et al., in which 336 patients with dyspnea were enrolled in the Emergency Departments of three University Hospitals in Italy.These two studies confirm the prognostic role of copeptin in patients with dyspnea due to heart failure but, while Winther et al. performed the copeptin measurements only at admission, Vetrone et al. evaluated the time-course of copeptin plasma concentration from the admission to the hospital discharge. The results showed a better performance of copeptin measured at discharge as prognostic biomarker compared to copeptin at hospital admission; similarly, a lower reduction or an increase in copeptin concentration from admission to discharge was a strong prognostic predictor of unfavorable outcome. In our opinion this is a very important result, opening new perspectives for the use of copeptin as prognostic marker in HF patients.


Asunto(s)
Glicopéptidos/sangre , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Aguda , Biomarcadores/sangre , Insuficiencia Cardíaca/epidemiología , Humanos , Estudios Multicéntricos como Asunto/métodos , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología
18.
Adv Exp Med Biol ; 996: 155-168, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29124698

RESUMEN

Vitamin D is a fat soluble hormone, with a well described role in bone health and calcium/phosphate metabolism. Recent evidences have related vitamin D to other physiological functions and pathological conditions. Specifically, vitamin D has widely proven activities on immune system and evidences suggest that it may be implicated in the pathogenesis of rheumatoid arthritis (RA). The relationship between vitamin D and RA is complex, also because a deficitary vitamin D status, which is very common in RA patients, can contribute to the increased risk of osteoporosis typical of RA. In this chapter, will be described and discussed the main aspects of the relationship between RA and vitamin D.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Suplementos Dietéticos , Osteoporosis/prevención & control , Deficiencia de Vitamina D/tratamiento farmacológico , Vitamina D/uso terapéutico , Animales , Artritis Reumatoide/epidemiología , Artritis Reumatoide/metabolismo , Suplementos Dietéticos/efectos adversos , Estado de Salud , Humanos , Osteoporosis/epidemiología , Osteoporosis/metabolismo , Factores de Riesgo , Luz Solar , Rayos Ultravioleta , Vitamina D/efectos adversos , Vitamina D/metabolismo , Vitamina D/efectos de la radiación , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/metabolismo
19.
Int J Mol Sci ; 17(11)2016 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-27801848

RESUMEN

Growth arrest specific 6 (Gas6) is a multimodular circulating protein, the biological actions of which are mediated by the interaction with three transmembrane tyrosine kinase receptors: Tyro3, Axl, and MerTK, collectively named TAM. Over the last few decades, many progresses have been done in the understanding of the biological activities of this highly pleiotropic system, which plays a role in the regulation of immune response, inflammation, coagulation, cell growth, and clearance of apoptotic bodies. Recent findings have further related Gas6 and TAM receptors to neuroinflammation in general and, specifically, to multiple sclerosis (MS). In this paper, we review the biology of the Gas6/TAM system and the current evidence supporting its potential role in the pathogenesis of MS.


Asunto(s)
Péptidos y Proteínas de Señalización Intercelular/genética , Esclerosis Múltiple/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas Receptoras/genética , Animales , Humanos , Inflamación/genética , Inflamación/patología , Esclerosis Múltiple/patología , Transducción de Señal , Tirosina Quinasa c-Mer , Tirosina Quinasa del Receptor Axl
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