Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 64.932
Filtrar
1.
Nat Commun ; 12(1): 2368, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888696

RESUMO

Endothelial cells play a key role in the regulation of disease. Defective regulation of endothelial cell homeostasis may cause mesenchymal activation of other endothelial cells or neighboring cell types, and in both cases contributes to organ fibrosis. Regulatory control of endothelial cell homeostasis is not well studied. Diabetes accelerates renal fibrosis in mice lacking the endothelial glucocorticoid receptor (GR), compared to control mice. Hypercholesterolemia further enhances severe renal fibrosis. The fibrogenic phenotype in the kidneys of diabetic mice lacking endothelial GR is associated with aberrant cytokine and chemokine reprogramming, augmented Wnt signaling and suppression of fatty acid oxidation. Both neutralization of IL-6 and Wnt inhibition improve kidney fibrosis by mitigating mesenchymal transition. Conditioned media from endothelial cells from diabetic mice lacking endothelial GR stimulate Wnt signaling-dependent epithelial-to-mesenchymal transition in tubular epithelial cells from diabetic controls. These data demonstrate that endothelial GR is an essential antifibrotic molecule in diabetes.


Assuntos
Nefropatias Diabéticas/patologia , Endotélio/patologia , Hipercolesterolemia/complicações , Túbulos Renais/patologia , Receptores de Glucocorticoides/deficiência , Adrenalectomia , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Células Endoteliais/patologia , Endotélio/citologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Ácidos Graxos/metabolismo , Fibrose , Glucocorticoides/metabolismo , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Hipercolesterolemia/patologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Túbulos Renais/citologia , Masculino , Camundongos , Camundongos Knockout para ApoE , Oxirredução , Receptores de Glucocorticoides/genética , Estreptozocina/administração & dosagem , Estreptozocina/toxicidade , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética
2.
Int J Mol Sci ; 22(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33925779

RESUMO

Paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS) is a new systemic inflammatory disease that mainly affects children. Its course in many features resembles that of acute rheumatic fever (ARF). Therefore, it is interesting that the experiences with ARF can be used in the management of patients with PIMS-TS. The aim of the article is to analyse the current data on PIMS-TS in relation to ARF. PIMS-TS and ARF are associated with an abnormal immune response to specific pathogens (SARS-CoV-2 and group A streptococcus, respectively). The main symptoms of both diseases are fever and cardiac involvement. Current therapy for PIMS-TS is based on anti-inflammatory treatment: intravenous immunoglobulin (first-line), intravenous glucocorticoids (second-line), or biological therapy (third-line; including interleukin [IL]-1 antagonists, IL-6 receptor blockers, and anti-tumour necrosis factor agents). Vaccination might be good prophylaxis, but the efficacy and safety of the vaccines against SARS-CoV-2 have not yet been established in children. Interesting insights may be gained by considering PIMS-TS in light of what is known of ARF due to their similar courses, but there are still many unanswered questions surrounding this disease and its pathogenesis.


Assuntos
/patologia , Febre Reumática/patologia , Síndrome de Resposta Inflamatória Sistêmica/patologia , /complicações , /etiologia , /imunologia , Citocinas/metabolismo , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Febre Reumática/microbiologia , Streptococcus pyogenes/patogenicidade , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/etiologia
3.
Praxis (Bern 1994) ; 110(6): 285-292, 2021 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-33906446

RESUMO

CME: Giant Cell Arteritis Abstract. Giant cell arteritis (GCA) is the most common vasculitis among patients over the age of 50. Mainly large vessels are targeted. GCA can be differentiated into cranial and extra-cranial types; thus the symptoms can range from headache, blurred vision and jaw claudication to non-specific symptoms like fatigue, polymyalgia and fever. Complications such as an irreversible loss of vision are critical, which is why timeous diagnosis and treatment are essential. There are some recommendations for treatment, but no defined guidelines exist. Steroids have been the standard treatment for the past six decades and remain so, but side effects are common. Tocilizumab represents an alternative and more effective and safer treatment.


Assuntos
Arterite de Células Gigantes , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides , Cefaleia , Humanos , Mialgia , Transtornos da Visão
4.
Am J Case Rep ; 22: e930733, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33907174

RESUMO

BACKGROUND Intravenous (IV) dexamethasone is widely used in critical illness, chemotherapy, or severe COVID-19. Although glucocorticoid-induced hyperglycemia (GCIH) is well-known, there is no report describing the glycemic profile following a single dose of IV dexamethasone as captured on continuous glucose monitoring (CGM) in a patient with diabetes treated with insulin. CASE REPORT A 70-year-old woman with diabetes and pancreatic adenocarcinoma was treated with chemotherapy containing dexamethasone every other week. CGM data of 23 cycles revealed a reproducible triphasic glycemic pattern consisting of a constant hyperglycemia period, followed by a transient improvement, and ending with another hyperglycemic plateau. Given this recurrent pattern, basal insulin and correction insulin were adjusted with subsequent GCIH attenuation. CONCLUSIONS This is the first report of CGM glycemic profile following recurring doses of IV dexamethasone in a patient with diabetes treated with basal-bolus insulin. The understanding of triphasic glycemic pattern allows optimal glycemic management.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Hormonais/efeitos adversos , Automonitorização da Glicemia/efeitos adversos , Dexametasona/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/induzido quimicamente , Insulina/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Administração Intravenosa , Idoso , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Glicemia , Dexametasona/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/patologia
5.
Eur Rev Med Pharmacol Sci ; 25(8): 3325-3337, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33928620

RESUMO

Since the reports in Wuhan (China), in December 2019, of the first cluster of cases of pneumonia caused by the new Coronavirus called 2019-nCoV or SARS-CoV-2, there has been a pandemic spread of the infection. By now, we have no specific therapy to counteract this emergency. The latest epidemiological data suggest that children are just as likely as adults to get infected by the virus. Most of them show mild clinical pictures or are completely asymptomatic, but there is an increased risk for severe disease in infancy (<12 months of age) and in children with underlying medical conditions. In this article, research achievements on the treatment of pediatric SARS-CoV-2 infection are examined.


Assuntos
Antivirais/uso terapêutico , Fatores Imunológicos/uso terapêutico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Adolescente , Fatores Etários , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/uso terapêutico , Portador Sadio , Criança , Pré-Escolar , Cloroquina/uso terapêutico , Terapia de Substituição Renal Contínua , Combinação de Medicamentos , Oxigenação por Membrana Extracorpórea , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Recém-Nascido , Interferon-alfa/uso terapêutico , Lopinavir/uso terapêutico , Oseltamivir/uso terapêutico , Receptores de Superfície Celular/uso terapêutico , Respiração Artificial , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , Índice de Gravidade de Doença , Trombose/prevenção & controle
8.
Medicine (Baltimore) ; 100(15): e25584, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847689

RESUMO

INTRODUCTION: Prednisone (10 mg/d) is often used in combination with docetaxel or abiraterone in the treatment of advanced prostate cancer. LATITUDE studies have confirmed that the combination of abiraterone and prednisone (5 mg/d) can be used for the treatment of newly diagnosed high-risk metastatic castration-sensitive prostate cancer, and have achieved satisfactory results. However, it has not been reported that abiraterone combined with prednisone (5 mg/d) in the treatment of metastatic castration-resistant prostate cancer (mCRPC). PATIENT CONCERNS: Here, we present a case of high-risk advanced prostate cancer with old pulmonary tuberculosis (PTB). The patient developed a relapse of old tuberculosis in both lungs that were discovered following 14 months of continuous application of prednisone (10 mg/d). DIAGNOSIS: The histopathological findings showed prostate adenocarcinoma carcinoma with a Gleason score of 10 (5+5). Further laboratory investigations were suggestive of positive mycobacterium tuberculosis complex DNA in pleural effusion and sputum. INTERVENTIONS: The patient underwent endocrine therapy, chemotherapy of docetaxel plus prednisone, radiotherapy, and abiraterone combined with prednisone treatment, but he eventually developed into the mCRPC stage. Then, prednisone was reduced to 5 mg/d plus abiraterone, and combined with anti-tuberculosis treatment according to multi-disciplinary diagnosis and treatment. OUTCOME: Two months later, pleural effusion and atelectasis were relieved, and PSA was remained stable at a low level. The patient achieved complete remission. CONCLUSION: We cannot, with complete certainty, say that this patient, or any patient, developed old PTB recurrence due to the use of prednisone. Based on the current evidence, endocrine therapy is the foundation, radiotherapy can reduce the tumor load, and early application of abiraterone is beneficial to survival for the high-risk mCRPC. The long-term use of prednisone can be appropriately reduced in mCRPC with old PTB, and a satisfactory curative effect can be achieved. More prospective trials are warranted before a definite recommendation could be drawn.


Assuntos
Glucocorticoides/administração & dosagem , Mycobacterium , Prednisona/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Idoso , Humanos , Masculino , Ilustração Médica , Neoplasias de Próstata Resistentes à Castração/microbiologia , Recidiva , Resultado do Tratamento , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/microbiologia
9.
Nat Commun ; 12(1): 1987, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790284

RESUMO

A widely regarded model for glucocorticoid receptor (GR) action postulates that dimeric binding to DNA regulates unfavorable metabolic pathways while monomeric receptor binding promotes repressive gene responses related to its anti-inflammatory effects. This model has been built upon the characterization of the GRdim mutant, reported to be incapable of DNA binding and dimerization. Although quantitative live-cell imaging data shows GRdim as mostly dimeric, genomic studies based on recovery of enriched half-site response elements suggest monomeric engagement on DNA. Here, we perform genome-wide studies on GRdim and a constitutively monomeric mutant. Our results show that impairing dimerization affects binding even to open chromatin. We also find that GRdim does not exclusively bind half-response elements. Our results do not support a physiological role for monomeric GR and are consistent with a common mode of receptor binding via higher order structures that drives both the activating and repressive actions of glucocorticoids.


Assuntos
DNA/metabolismo , Estudo de Associação Genômica Ampla/métodos , Multimerização Proteica , Receptores de Glucocorticoides/química , Receptores de Glucocorticoides/metabolismo , Animais , Cromatina/genética , Cromatina/metabolismo , DNA/genética , Regulação da Expressão Gênica , Glucocorticoides/metabolismo , Humanos , Camundongos , Mutação , Ligação Proteica , Receptores de Glucocorticoides/genética , Elementos de Resposta/genética , Transdução de Sinais/genética
12.
J Am Vet Med Assoc ; 258(9): 999-1006, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33856871

RESUMO

CASE DESCRIPTION: 4 dogs, 7.5 to 10 years of age, were presented for evaluation of signs of chronic cervical pain and forelimb lameness secondary to cervical foraminal intervertebral disk protrusion (IVDP). All dogs were refractory to ≥ 2 weeks of conservative management including strict rest and pain management with anti-inflammatory drugs, methocarbamol, and gabapentin. CLINICAL FINDINGS: The MRI findings included left foraminal IVDP at C2-3 causing mild C3 nerve root compression (dog 1), multifocal degenerative disk disease with mild focal left-sided disk protrusion at C6-7 without associated spinal cord or nerve root compression (dog 2), left foraminal C6-7 IVDP with suspected focal spinal cord atrophy or mild compression (dog 3), and right foraminal C6-7 IVDP and multifocal cervical intervertebral disk degeneration with annulus fibrosus protrusion (dog 4). TREATMENT AND OUTCOME: Ultrasound-guided paravertebral perineural injections with methylprednisolone acetate (1 mg/kg [0.45 mg/lb]) at the C3 nerve root in dog 1 and at the C7 nerve root in the other 3 dogs were performed. Injections were repeated at intervals of 4 weeks to 3 months on the basis of clinical response. None of the dogs had any complications from the procedures. For dogs 1 and 4, there was complete resolution of lameness and signs of cervical pain following perineural injections, and for dog 3, there was complete resolution of lameness and only minimal residual cervical pain. Dog 2 did not have long-lasting improvement. CLINICAL RELEVANCE: Findings indicated that ultrasound-guided paravertebral perineural injection can be an effective treatment of cervical foraminal IVDP for some dogs. Additional studies to determine appropriate case selection and better assess the overall success rate and risks associated with this technique are warranted.


Assuntos
Doenças do Cão , Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Disco Intervertebral , Animais , Vértebras Cervicais , Doenças do Cão/tratamento farmacológico , Cães , Glucocorticoides , Degeneração do Disco Intervertebral/veterinária , Deslocamento do Disco Intervertebral/veterinária , Cervicalgia/veterinária , Ultrassonografia de Intervenção/veterinária
14.
RMD Open ; 7(1)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33790049

RESUMO

BACKGROUND: The CHIC study (COVID-19 High-intensity Immunosuppression in Cytokine storm syndrome) is a quasi-experimental treatment study exploring immunosuppressive treatment versus supportive treatment only in patients with COVID-19 with life-threatening hyperinflammation. Causal inference provides a means of investigating causality in non-randomised experiments. Here we report 14-day improvement as well as 30-day and 90-day mortality. PATIENTS AND METHODS: The first 86 patients (period 1) received optimal supportive care only; the second 86 patients (period 2) received methylprednisolone and (if necessary) tocilizumab, in addition to optimal supportive care. The main outcomes were 14-day clinical improvement and 30-day and 90-day survival. An 80% decline in C reactive protein (CRP) was recorded on or before day 13 (CRP >100 mg/L was an inclusion criterion). Non-linear mediation analysis was performed to decompose CRP-mediated effects of immunosuppression (defined as natural indirect effects) and non-CRP-mediated effects attributable to natural prognostic differences between periods (defined as natural direct effects). RESULTS: The natural direct (non-CRP-mediated) effects for period 2 versus period 1 showed an OR of 1.38 (38% better) for 14-day improvement and an OR of 1.16 (16% better) for 30-day and 90-day survival. The natural indirect (CRP-mediated) effects for period 2 showed an OR of 2.27 (127% better) for 14-day improvement, an OR of 1.60 (60% better) for 30-day survival and an OR of 1.49 (49% better) for 90-day survival. The number needed to treat was 5 for 14-day improvement, 9 for survival on day 30, and 10 for survival on day 90. CONCLUSION: Causal inference with non-linear mediation analysis further substantiates the claim that a brief but intensive treatment with immunosuppressants in patients with COVID-19 and systemic hyperinflammation adds to rapid recovery and saves lives. Causal inference is an alternative to conventional trial analysis, when randomised controlled trials are considered unethical, unfeasible or impracticable.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Proteína C-Reativa/imunologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Metilprednisolona/uso terapêutico , /imunologia , Causalidade , Síndrome da Liberação de Citocina/imunologia , Estudo Historicamente Controlado , Humanos , Inflamação/imunologia , Mortalidade , Taxa de Sobrevida , Resultado do Tratamento
15.
Br J Hosp Med (Lond) ; 82(3): 1-9, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33792391

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread and have grave health and socioeconomic consequences worldwide. Researchers have raced to understand the pathophysiological mechanisms underpinning the disease caused by SARS-CoV-2 so that effective therapeutic targets can be discovered. This review summarises the key pharmacotherapies that are being investigated for treatment of COVID-19, including antiviral, immunomodulator and anticoagulation strategies.


Assuntos
Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Glucocorticoides/uso terapêutico , Fatores Imunológicos/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Azetidinas/uso terapêutico , Colchicina/uso terapêutico , Dexametasona/uso terapêutico , Humanos , Imunização Passiva , Ivermectina/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico
16.
Medicina (Kaunas) ; 57(3)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799535

RESUMO

Background and Objectives: On 24 March 2020, the United States Food and Drug Administration (FDA) announced the approval of convalescent plasma therapy for critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergency investigational new drug. This pilot study from Romania aimed to determine if convalescent plasma transfusion can be beneficial in the treatment of selected critically ill patients diagnosed with a SARS-CoV-2 infection. Materials and Methods: Donor and receiver eligibility for critically ill coronavirus disease 2019 (COVID-19) patients was based on Romanian guidelines issued at the time of the study. Here, we describe the evolution of a total of five eligible patients diagnosed with COVID-19 who received convalescent plasma (CP) in Romania. Results: In spite of our efforts and convalescent plasma administration, three of the five patients did not survive, while the other two recovered completely. Over the course of our five-day laboratory record, the surviving patients had significantly lower values for C-reactive protein, interleukin-6, and white blood cells. Conclusions: This pilot study provides insufficient evidence to determine the efficacy of convalescent plasma use as a therapeutic option for critically ill COVID-19 patients.


Assuntos
/terapia , Adulto , Antibacterianos/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Proteína C-Reativa/metabolismo , /fisiopatologia , Estado Terminal , Glucocorticoides/uso terapêutico , Humanos , Imunização Passiva/métodos , Interleucina-6/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Romênia , Resultado do Tratamento
17.
Medicina (Kaunas) ; 57(3)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803690

RESUMO

The COVID-19 pandemic dramatically changed medical care. Healthcare professionals are faced with new issues. Patients who survived COVID-19 have plenty of different continuing symptoms, of which the most common are fatigue and breathlessness. It is not well known how to care for patients with persistent or worsening respiratory symptoms and changes on chest X-ray following COVID-19 pneumonia. In this article, we talk about a subgroup of patients with organizing pneumonia following COVID-19 pneumonia that could be effectively treated with systemic glucocorticoids. It is important that patients with COVID-19 pneumonia be followed-up at least three weeks after diagnosis, in order to recognize early lung damage. We are providing a management algorithm for early diagnosis of lung diseases after COVID-19 pneumonia.


Assuntos
/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Algoritmos , Biópsia , /tratamento farmacológico , Angiografia por Tomografia Computadorizada , Gerenciamento Clínico , Diagnóstico Precoce , Glucocorticoides/uso terapêutico , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Capacidade de Difusão Pulmonar , Espirometria , Tomografia Computadorizada por Raios X , Teste de Caminhada
18.
Wiad Lek ; 74(2): 247-251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33813480

RESUMO

OBJECTIVE: The aim: Is to study the morphological features of rats' hearts after prenatal administration of glucocorticoids. PATIENTS AND METHODS: Materials and methods: In this study we used histological, immunohistochemical, electron-microscopic and statistical research methods. RESULTS: Results: It is found that at 30th day after birth in rats after intrafetal introduction of dexamethasone in myocardium a relative area occupied by arterial vessels is significantly smaller in comparison with control. Absolute and relative number of Ki-67+-cardiomyocytes in the myocardium of experimental rats is reduced throughout the second week after birth and is significantly less compared to the control group. In the nuclei of cardiomyocytes of experimental rats is rendered the greater amount of heterochromatin in comparison with cardiomyocytes of the control group where euchromatin prevails. CONCLUSION: Conclusions: After intrafetal injection of dexametazone changes in dynamics and significantly smaller index of relative area occupied by arterial vessels in ventricular myocardium at the 30th day after birth are observed; the absolute and relative number of Ki-67+ -cardiomyocytes in myocardium decreases during the second week after birth and is significantly lower compared to the control group; in the nuclei of cardiomyocytes of experimental rats a greater amount of heterochromatin is visualized, and in cardiomyocytes of the control group - euchromatin.


Assuntos
Miocárdio , Miócitos Cardíacos , Dexametasona , Feminino , Glucocorticoides , Ventrículos do Coração , Humanos , Gravidez
19.
Wiad Lek ; 74(2): 303-309, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33813491

RESUMO

OBJECTIVE: The aim: To study the peculiarities of bone mineral density in the Ukrainian population of women of different reproductive age with systemic lupus erythematosus and to evaluate its connection with traditional and specific (typical for systemic lupus erythematosus) risk factors. PATIENTS AND METHODS: Materials and methods: A total of 91 women with systemic lupus erythematosus and 29 healthy individuals were examined. Along with the clinical study of the activity and severity of the disease, the serum levels of interleukin-6 were determined by the enzyme immunoassay. The peculiarities of bone mineral density were studied using dual-energy X-ray absorptiometry. The presence of fractures was evaluated by the X-ray method. RESULTS: Results: Patients with systemic lupus erythematosus frequently suffer from reduced bone mineral density. Reduced bone mineral density and the appearance of fragility fractures are associated with patients' age, disease duration, damage index, inflammatory activity, and cumulative dose of glucocorticoids. CONCLUSION: Conclusions: Progressive reduced bone mineral density in patients with systemic lupus erythematosus occurs not only during the aging process of a woman, but is also associatedwith a number of systemic lupus erythematosus - related osteoporosis risk factors.


Assuntos
Lúpus Eritematoso Sistêmico , Osteoporose , Absorciometria de Fóton , Densidade Óssea , Feminino , Glucocorticoides , Humanos , Lúpus Eritematoso Sistêmico/complicações , Osteoporose/epidemiologia , Osteoporose/etiologia
20.
Int J Mol Sci ; 22(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807481

RESUMO

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRß, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRß has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRß actions are restricted to its dominant-negative effects on GRα-mediated responses, GRß has been shown to have intrinsic activities and "directly" regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRß has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRß-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRß and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.


Assuntos
Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/fisiologia , Processamento Alternativo/efeitos dos fármacos , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Humanos , Isoformas de Proteínas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...