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1.
An Bras Dermatol ; 94(4): 416-421, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644613

RESUMO

BACKGROUND: Frontal fibrosing alopecia is a condition of unknown origin, histologically similar to classic lichen planopilaris and generally observed in postmenopausal women with alopecia of the frontal-temporal hairline. OBJECTIVES: To describe the clinical, dermatoscopic, and histopathological characteristics and the treatment used in patients who have frontal fibrosing alopecia at the Alopecia Outpatient Clinic in a university hospital. METHODS: Retrospective descriptive study performed by reviewing medical charts and biopsies of the scalp. RESULTS: Sixteen patients were analyzed, all of them female, 93.75% of them postmenopausal, and 56.25% brown-skinned. All had frontal alopecia (100%), followed by temporal alopecia (87.5%) and madarosis (87.5%). On dermatoscopy, perifollicular erythema and tubular scales were found as a sign of disease activity. Of the patients, 68.75% had associated autoimmune diseases, including lupus, thyroid disease and vitiligo. Of the 13 biopsies from 8 patients, 10 showed microscopic aspects compatible with frontal fibrosing alopecia. Laboratory tests did not show major abnormalities and minoxidil was the most used treatment. STUDY LIMITATION: Data collection limited by the study's retrospective design associated to flaws while filling in the medical charts and absence in standards to the collection and processing of the pathology and histopathological examination. CONCLUSIONS: A demographical, clinical, and histopathological description of 16 patients diagnosed with frontal fibrosing alopecia, which remains a challenging disease, of unknown origin, and frequently associated with autoimmune diseases. This study reinforces literary findings. However, more research is needed to establish the pathogenesis and effective treatments.


Assuntos
Alopecia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alopecia/tratamento farmacológico , Biópsia , Dermoscopia/métodos , Feminino , Fibrose , Folículo Piloso/patologia , Hospitais Universitários , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Couro Cabeludo/patologia
3.
Vestn Oftalmol ; 135(4): 19-26, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31573553

RESUMO

INTRODUCTION: Fibrosis is the most important pathologic condition involved in undesirable outcomes of dacryocystorhinostomy. A number of biochemical factors are currently known to have an effect on wound healing by promoting excessive scarring. Isoforms of transforming growth factor ß (TGF-ß1) are considered the 'main' pro-fibrotic factor, but wound healing is also affected by other cytokines such as connective tissue growth factor (CTGF), which stimulates fibrosis, and fibroblast growth factor (FGF-2), which acts as antagonist to it. PURPOSE: To investigate correlations between endoscopic endonasal dacryocystorhinostomy outcomes and certain mediators of fibrosis. MATERIAL AND METHODS: The study included 45 cases of endoscopic endonasal dacryocystorhinostomy. The patients were grouped according to surgery outcome: patients with unsuccessful surgical treatment were assigned to group 1 (n=10); patients with successful surgical treatment - to group 2 (n=34). One patient was excluded from the study. Full-layer biopsy specimen were taken from patients' nasal mucosa before the surgery. TGF-ß1, TGF-ß2, TGF-ß3, CTGF, FGF-2 concentrations were evaluated using ELISA and normalized by total protein concentration. RESULTS: Surgical failure was observed in 10 cases (22.72%). CTGF concentration was significantly correlated with negative outcome (p<0.05) and was elevated in most specimen obtained from group 1. No significant correlation was noted between the concentrations of other evaluated cytokines in nasal mucosa specimens and the surgical outcome. CONCLUSION: The study found a correlation between CTGF concentration in nasal mucosa and dacryocystorhinostomy outcome, which supports the hypothesis suggested by several authors linking dacryocystorhinostomy failure with chronic inflammation in nasal mucosa.


Assuntos
Dacriocistorinostomia , Citocinas , Fibrose , Humanos , Inflamação , Fator de Crescimento Transformador beta
4.
Medicine (Baltimore) ; 98(41): e17551, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593137

RESUMO

RATIONALE: Refractory edema is characterized by persistent swelling which does not react to diuretic use and sodium restriction. Traditional herbal medicine, Gwack Rhyung Tang and Chunggan extract effectively treated refractory lower limb edema caused by cirrhosis and improved liver function. PATIENT CONCERNS: A 64-year-old male patient with a history of hypertension, diabetes mellitus, hepatic encephalopathy, and cellulitis presented lower limb edema which did not react to diuretics for more than 7 months. DIAGNOSES: Refractory edema caused by cirrhosis. INTERVENTIONS: The patient was treated for 25 days using Gwack Rhyung Tang and Chunggan extract. OUTCOMES: Loss of body weight, decrease in circumferences of both lower limb and improvement of liver function biochemistry results are checked. There was no recurrence or aggravation of the condition up to 3 weeks of follow-up periods. LESSONS: Traditional herbal medicine can be an effective alternative for refractory edema due to cirrhosis with improving liver function.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Edema/tratamento farmacológico , Medicina Tradicional/métodos , Diuréticos/uso terapêutico , Resistência a Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Fibrose/complicações , Medicina Herbária , Humanos , Extremidade Inferior/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
5.
Clin Exp Rheumatol ; 37 Suppl 119(4): 3-14, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587697

RESUMO

Systemic sclerosis (SSc) is a complex disorder characterised by the involvement of small arteries, microvessels and connective tissue, with deposition of fibrotic tissue and microvascular obliteration in the skin and internal organs. Due to the multifaceted nature of the disease, several articles are published in the medical literature every year, aimed at exploring different aspects of the pathogenesis, internal organ involvement and clinical aspects, and possible therapeutic approaches. In this article we have reviewed the literature on SSc of the past year, with the aim of identifying novel approaches that may help the treating physician in the clinical management of patients.


Assuntos
Microvasos/patologia , Escleroderma Sistêmico , Vasos Sanguíneos/patologia , Fibrose , Humanos , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia , Pele
6.
J Biol Regul Homeost Agents ; 33(5): 1337-1345, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637903

RESUMO

The effects of miR-145 (microRNA 145) on M. pneumoniae (MP)-infected MRC-5 (Medical Research Council cell strain 5) cell TGF-ß/Smad (transforming growth factor beta/Smad) fibrosis pathway were explored through constructing MP-infected MRC-5 cell models. In addition, the qPCR (quantitative real-time polymerase chain reaction) and Western blot were applied to detect the mRNA and protein expressions of miR-145, TGF-ß1 (transforming growth factor beta 1), Smad3, Smad4, MMP2 (matrix metalloproteinase 2), FN1 (fibronectin 1), ELN (elastin) and COLI α1 (collagen type I alpha 1) signaling molecules in TGF-ß/Smad fibrosis pathway. The results showed that the expression of miR-145 in MRC-5 cells was significantly increased after MP infection. In addition, miR-145 inhibited the fibrosis promoting TGF-ß/Smad pathway by targeting Smad3, a key factor in the TGF-ß/Smad pathway. It can be concluded that, in the process of MP infection, the expression of miR-145 is stimulated to negatively regulate the fibrosis-promoting pathway of TGF-ß/Smad.


Assuntos
Fibroblastos/patologia , MicroRNAs/metabolismo , Mycoplasma pneumoniae , Proteínas Smad/metabolismo , Linhagem Celular , Fibroblastos/microbiologia , Fibrose , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
7.
Int Heart J ; 60(5): 1147-1153, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484872

RESUMO

Heart failure causes increased venous pressure, leading to liver dysfunction. The fibrosis-4 index is a simple index for liver fibrosis and has been reported to be useful for predicting prognosis in heart failure; however, its impact on patients with pulmonary hypertension due to left heart disease (PH-LHD) has not yet been fully elucidated.We enrolled consecutive 230 hospitalized patients who had been diagnosed as having PH-LHD. The fibrosis-4 index was calculated as follows: [aspartate transaminase (U/L) × age]/[alanine transaminase 1/2 (U/L) × platelet count (109/L) ]. We followed patients for all-cause mortality during the follow-up period (mean 1112 ± 822 days).The patients were divided into tertiles based on their fibrosis-4 index: the first tertile 0.335 to 1.381; the second tertile 1.391 to 2.311; and the third tertile 2.323 to 14.339. Compared with the first tertile, the third tertile had lower estimated glomerular filtration rates and hemoglobin levels. All-cause mortality was significantly higher in the third than in the first tertile. In a Cox proportional hazard model, the fibrosis-4 index was a predictor of all-cause mortality in PH-LHD patients (HR 1.212, 95% CI 1.099-1.337, P < 0.001).The fibrosis-4 index is associated with kidney function, anemia, and high mortality in PH-LHD patients.


Assuntos
Causas de Morte , Insuficiência Cardíaca/mortalidade , Hipertensão Pulmonar/mortalidade , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/patologia , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Fibrose/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Hospitais Universitários , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Análise de Sobrevida , Disfunção Ventricular Esquerda/sangue
8.
Urologiia ; (4): 96-100, 2019 Sep.
Artigo em Russo | MEDLINE | ID: mdl-31535813

RESUMO

Penile prosthesis implantation is a treatment choice in patients with erectile dysfunction (ED) accompanied by cavernous fibrosis. Methods for creation of space for penile cylinders during prosthesis implantation in patents with total cavernous fibrosis are still under discussion, considering high risk of complications and decrease in penile size. In the presented clinical case, a new surgical technique for performing a three-piece penile prosthesis implantation through subcoronal approach in patient with ED, complicated by total cavernous fibrosis, is described. This clinical case represents our first experience of excavation excision of scar tissue in cavernous bodies through an innovative subcoronoral approach. As a result of performing of excavation excision of scar tissue in cavernous bodies, capacious spaces were created which allowed to use a three-piece prosthesis with a standard cylinder diameter. It ensured good long-term functional and cosmetic results. The first experience of excavation excision of fibrotic cavernous bodies during inflatable penile prosthesis implantation through subcoronal approach suggests its potential efficacy and safety in patients with ED and total cavernous fibrosis.


Assuntos
Disfunção Erétil , Implante Peniano , Prótese de Pênis , Fibrose , Humanos , Masculino , Pênis
9.
Clin Exp Rheumatol ; 37 Suppl 119(4): 141-146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31498062

RESUMO

Systemic sclerosis (SSc) is a complex autoimmune disease characterised by fibrosis of the skin and multiple internal organs. Interleukin 33 (IL-33) has recently been investigated as a potential key player in the pathogenesis of SSc and other fibrotic diseases, owing to its effects on tissue fibrosis. Understanding how IL-33 is regulated and how it contributes to the development of fibrosis will be important to elucidate disease pathogenesis and may shed light on new areas for therapeutic development for patients. Here we discuss the recent research progress in our understanding of the role and the underlying mechanisms of IL-33/ST2 signaling pathway in SSc and other fibrotic diseases.


Assuntos
Interleucina-33 , Receptores de Superfície Celular/fisiologia , Escleroderma Sistêmico , Transdução de Sinais/fisiologia , Fibrose/metabolismo , Humanos , Interleucina-33/metabolismo , Receptores de Interleucina/metabolismo , Escleroderma Sistêmico/metabolismo , Pele
10.
Autoimmun Rev ; 18(11): 102396, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520794

RESUMO

Systemic Sclerosis (SSc) pathogenesis involves multiple immunological, vascular and fibroproliferative abnormalities that contribute to a severe and complex clinical picture. Vasculopathy and fibroproliferative alterations are two hallmark pathological processes in SSc that are responsible for the most severe clinical manifestations of the disease and determine its clinical outcome and mortality. However, the pathogenesis of SSc vasculopathy and of the uncontrolled SSc fibrotic process remain incompletely understood. Recent investigations into the molecular pathways involved in these processes have identified an important role for epigenetic processes that contribute to overall disease progression and have emphasized microRNAs (miRNAs) as crucial epigenetic regulators. MiRNAs hold unique potential for elucidating SSc pathogenesis, improving diagnosis and developing effective targeted therapies for the disease. This review examines the important role that miRNAs play in the development and regulation of vascular and fibroproliferative alterations associated with SSc pathogenesis and their possible participation in the establishment of pathogenetic connections between these two processes. This review also emphasizes that further understanding of the involvement of miRNA in SSc fibrosis and vasculopathy will very likely provide novel future research directions and allow for the identification of groundbreaking therapeutic interventions within these processes. MiR-21, miR- 31, and miR-155 are of particular interest owing to their important involvement in both SSc vasculopathy and fibroproliferative alterations.


Assuntos
MicroRNAs , Escleroderma Sistêmico/genética , Doenças Vasculares/genética , Animais , Fibrose , Humanos
11.
J Assoc Physicians India ; 67(8): 26-30, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31562712

RESUMO

Background: : Systemic sclerosis (SSc) is a demyelinating disease of skin, subcutaneous tissue, muscles and internal organs, with fibrosis as an important pathological event. Aim: : To understand cytokine interplay of IL-1ß, IL-4 and IL-6 and their association with disease activity in treatment naïve active cases of systemic sclerosis from Western India. Methods: Twenty-five SSc patients as per ACR-EULAR 2013 criteria (classified based on pulmonary fibrosis and generalized fibrosis) and 25 age-sex matched controls were enrolled. Serum cytokine levels of IL-1ß, IL-4 and IL-6 were assessed by multiplex bead based immunoassay. Results: Ten patients had Interstitial lung disease (ILD), whereas, 16 patients had generalized fibrosis. Anti-nuclear antibodies were seen in 22 patients (88%); antiScl70 in 15 patients (60%) and anti-Centromere antibodies in 5 patients (20%). Serum levels of IL-1ß in patients were significantly higher than healthy controls (p=0.0006). IL-4 levels in all SSc patients were marginally raised (p=0.0102), while IL-6 levels were significantly raised (p<0.0001). IL-4 was found to be significantly raised in SSc patients with ILD (p=0.021) as compared to patients without ILD. IL-1ß (p=0.0293) and IL-4 (p<0.0001) were significantly higher in SSc patients with fibrosis. On the contrary, IL-6 levels in patients with fibrosis were found to be lower than in patients without fibrosis. Conclusion: Significantly raised cytokine levels among treatment naïve systemic sclerosis patients were found to be associated with higher disease severity in our study. Higher levels of IL-1ß and IL-6 indicated an active inflammatory status, whereas significantly raised IL-4 levels indicated at higher fibrotic activity.


Assuntos
Citocinas/metabolismo , Fibrose , Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Índia
12.
Biol Res ; 52(1): 50, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492196

RESUMO

BACKGROUND: Ureteral obstruction causes injury of the renal tissues and can irreversibly progress to renal fibrosis, with atrophy and apoptosis of tubular cells. The goal of the current study was to examine the effects of rhein on the apoptosis o renal tubular cells as well as renal fibrosis using a rodent model of unilateral ureteral obstruction (UUO). METHODS: UUO was induced through ureteral ligation, then animals received treatments with rhein or vehicle. The control rats only received sham operation. The renal tissue was harvested 1 week after surgery for assessment of kidney fibrosis. RESULTS: The expressions of collagen I and α-smooth muscle actin (α-SMA), as well as the severity of renal tubular apoptosis and fibrosis were time-dependently increased following UUO. Treatments with rhein partially inhibited such responses. Renal interstitial fibrosis was associated with STAT3 (signal transducer and activator of transcription 3) phosphorylation as well as altered expressions of Bax and Bcl2, both apoptosis-related proteins. Treatment with rhein also partly blocked these responses. CONCLUSION: These findings demonstrated that rhein mitigated apoptosis of renal tubular cell as well as renal fibrosis in a UUO rodent model. This curative effect is likely mediated via suppression of STAT3 phosphorylation.


Assuntos
Antraquinonas/administração & dosagem , Apoptose/efeitos dos fármacos , Rim/patologia , Obstrução Ureteral/prevenção & controle , Animais , Modelos Animais de Doenças , Progressão da Doença , Fibrose/metabolismo , Fibrose/patologia , Fibrose/prevenção & controle , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologia
13.
Adv Exp Med Biol ; 1178: 103-112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31493224

RESUMO

Coenzyme Q10 (CoQ10) is a vitamin-like substance which functions as an electron carrier within the mitochondrial respiratory chain, as well as serving as an important intracellular antioxidant. Most of the body's CoQ10 requirements are met by endogenous synthesis, although the capacity for CoQ10 production decreases substantially with increasing age. In this article we have reviewed the potential role of CoQ10 supplementation in the treatment of tissue fibrosis, which has been implicated in the age-related loss of function of various organs including the heart. Clinical studies have indicated that CoQ10 supplementation may decrease the level of cardiovascular fibrosis to which older individuals are subjected, and thereby improve cardiovascular function and reduce the risk of cardiovascular associated mortality. Although the factors responsible for the anti-fibrotic action of CoQ10 have yet to be fully elucidated, its antioxidant and anti-inflammatory functions are thought to be major contributors to its clinical efficacy in the treatment of this age-related disorder.


Assuntos
Antioxidantes , Ubiquinona/análogos & derivados , Antioxidantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Fibrose/tratamento farmacológico , Humanos , Ubiquinona/uso terapêutico
14.
Isr Med Assoc J ; 21(7): 471-474, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507123

RESUMO

BACKGROUND: Microvascular damage, clinically expressed by Raynaud's phenomenon, is generally the first symptom of the disease and the injured vascular cells, both endothelial and perivascular, may transdifferentiate to myofibroblasts, thus leading to collagen deposition in the tissue and consequent fibrosis. Systemic sclerosis (SSc, scleroderma) is complex disease characterized by autoimmunity, vasculopathy, and fibrosis. It has been shown that microvascular damage may be the first symptom of SSc. Injured endothelial cells and pericytes may transdifferentiate into myofibroblasts, the cells responsible for fibrosis and collagen deposition in the tissue. Based on these factors, the process of myofibroblast generation may link two pivotal events of SSc: microvascular damage and fibrosis. Understanding the development, differentiation, and function of myofibroblasts is therefore crucial to individuate early pathogenetic events and develop new therapeutic target for SSc, a condition in which no disease-modifying agents are available. The aim of this review was to discuss the possible origins of myofibroblasts in SSc, highlighting the process of endothelial mesenchymal transition and pericytes to myofibroblast transition and to show how these events may contribute to pathogenesis of the disease.


Assuntos
Miofibroblastos/citologia , Doença de Raynaud/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Diferenciação Celular/fisiologia , Células Endoteliais/citologia , Transição Epitelial-Mesenquimal/fisiologia , Fibrose/patologia , Humanos , Pericitos/citologia
16.
Expert Opin Drug Saf ; 18(10): 965-975, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31433252

RESUMO

Introduction: Treatment options for erectile dysfunction (ED) have evolved over the last two decades, particularly after the introduction of phosphodiesterase type-5 inhibitors (PDE5Is). The path, however, has not been straightforward with issues raised regarding safety and toxicity following ED treatments. Areas covered: A literature review was conducted on current evidence related to the safety of PDE5Is, intracavernosal injections and various older forms of oral therapies. Relevant trials were identified through a literature search of PubMed from 1980 to 2019. Expert opinion: PDE5Is are now recommended as the first line therapy for the treatment of ED due to their efficacy and tolerable side effects. Comparison of the various PDE5Is on safety has not been supported by prime evidence, and consequently, the negative aspects of each inhibitor appear the same as defined in the literature. Other means of therapies for ED are still in the running, and these also present a different range of side effects. While intracavernosal injections have potential to cause priapism and penile fibrosis, intraurethral alprostadil may result in more systematic side effects. Alternative topical ED therapies are generally limited with their local side effects.


Assuntos
Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5/administração & dosagem , Vasodilatadores/administração & dosagem , Alprostadil/administração & dosagem , Alprostadil/efeitos adversos , Animais , Fibrose/induzido quimicamente , Humanos , Injeções , Masculino , Doenças do Pênis/induzido quimicamente , Doenças do Pênis/patologia , Inibidores da Fosfodiesterase 5/efeitos adversos , Priapismo/induzido quimicamente , Vasodilatadores/efeitos adversos
17.
Clin Exp Rheumatol ; 37 Suppl 119(4): 69-75, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365333

RESUMO

OBJECTIVES: Relaxin is a potent anti-fibrotic hormone that has been tested to ameliorate fibrosis in systemic sclerosis (SSc), but with controversial results. The aim of the study is to sequence relaxin receptor gene RXFP1 and to assess its mRNA expression and protein levels in the skin of SSc patients and healthy subjects. METHODS: Fibroblasts were isolated from unaffected/affected skin samples of (n=16) limited-cutaneous-SSc-(LcSSc) and from affected ones of (n=4) diffuse-cutaneous-SSc-(DcSSc) patients. Fibroblasts from healthy subjects were used as controls. Sequencing of exonic target regions of interest for RXFP1 gene was performed, coupled with mRNA transcript variant analysis. RXFP1 mRNA and protein levels were assessed by quantitative-real-time-PCR-(qRT-PCR) and by immunocytochemistry-(ICC). Alpha-smooth-muscle-actin-(α-SMA) synthesis induced by transforming-growth-factor-beta-1-(TGF-ß1) stimulation was investigated in all fibroblasts with and without pre-treatment with serelaxin (a recombinant form of human relaxin-2 targeting the receptor RXFP1). RESULTS: Sequencing of RXFP1 gene showed no relevant mutations in all fibroblast populations. The analysis of mRNA transcripts revealed the presence of 13 different mRNA isoforms of RXFP1 (7 coding and 6 non-coding) upregulated in LcSSc/DcSSc-affected samples and not in LcSSc-unaffected and in healthy ones. On the contrary, ICC demonstrated the absence of RXFP1 in LcSSc/DcSSc-affected fibroblasts and the presence in LcSSc-unaffected and in healthy ones. To prove these findings, serelaxin pre-incubation was unable to counteract TGF-ß1-driven upregulation of α-SMA in LcSSc/DcSSc-affected fibroblasts only, but not in LcSSc-unaffected and healthy ones. CONCLUSIONS: The absence/altered expression of relaxin receptor RXFP1 in the affected fibroblasts of SSc patients could explain the inefficacy of relaxin-based anti-fibrotic treatments in the disease.


Assuntos
Fibroblastos/metabolismo , Relaxina , Esclerodermia Difusa , Escleroderma Sistêmico , Idoso , Feminino , Fibroblastos/patologia , Fibrose/metabolismo , Fibrose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Acoplados a Proteínas-G/metabolismo , Receptores de Peptídeos/metabolismo , Proteínas Recombinantes , Relaxina/metabolismo , Esclerodermia Difusa/metabolismo , Esclerodermia Difusa/patologia , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/patologia
18.
Zhonghua Xin Xue Guan Bing Za Zhi ; 47(8): 622-627, 2019 Aug 24.
Artigo em Chinês | MEDLINE | ID: mdl-31434433

RESUMO

Objective: To investigate the cardiovascular magnetic resonance (CMR) imaging characteristics and influence factors of aortic insufficiency (AI) patients with myocardial fibrosis. Method: This retrospective study included 59 AI patients who received CMR and transthoracic echocardiography (TTE) examinations from June 2011 to February 2015. AI patients were divided into 2 groups: bicuspid aortic valve (BAV) group (n=30) and non-BAV group (n=29). Patients were also divided into late gadolinium enhancement (LGE) group (n=27) and non-LGE group (n=32). The baseline clinical characteristics were collected through electronic medical records. Hemodynamic parameters such as grade of AI, cardiac functional parameters and LGE mass fraction (LGE%) were measured by CMR post-processing analysis. Kappa test was used to assess the consistency of AI severity between CMR and TTE, and the multivariate logistic regression analysis was performed to evaluate influence factors of myocardial fibrosis in AI patients. Results: (1) 56 (94.9%) patients were male, and the mean age was (44.2±11.0) years old. There was no significant difference in age and gender, hypertension, hyperlipidemia, alcoholic consumption between BAV and non-BAV group (all P>0.05). There were a higher proportion of smoking history (P=0.008), a lower body mass index (BMI) (P=0.020) in the LGE group than in the non-LGE group. (2) The accuracy of CMR in diagnosis of BAV was 96.7% (29/30) compared to the gold standard. In the BAV group, 20 patients (66.7%) were with fusion of left and right cusp (L-R), 5 patients (16.7%) were with fusion of right and noncoronary cusp (R-N), 5 patients (16.7%) were with fusion of left and noncoronary cusp (L-N); patients with BAV had larger left ventricular end diastolic volume index (LVEDVi), left ventricular end systolic volume index (LVESVi), higher proportion of LGE and lower left ventricular ejection fraction (LVEF) than those in non-BAV group (all P<0.05). There were 19 patients with BAV in the LGE group, the cases of L-R, R-N, L-N were 10 (52.6%), 5 (26.3%), and 4 (21.1%), respectively. In the non-LGE group, patients with BAV of L-R, R-N, L-N were 10 (90.9%), 0, and 1 (9.1%), respectively. Patients with LGE had lower body surface area (BSA), LVEF and larger LVEDVi, LVESVi, left ventricular mass index (LVMi) and higher proportion of BAV compared patients without LGE. In addition, the proportion of moderate and severe AI patients was significantly higher in BAV group than in non-BAV group (P=0.009). (3) The consistency of CMR and TTE in evaluating the severity of AI patients: the agreement between TTE and CMR regarding AI severity was satisfactory (kappa value was 0.624, 95%CI 0.402-0.831, P<0.001). (4) The linear regression analysis demonstrated a negative correlation between LVEF and LGE% in BAV and non-BAV group (P<0.001). The multivariate logistic regression analysis showed that the presence of BAV was an independent risk factor of left ventricucar fibrosis (OR=5.050, 95%CI 1.220-20.908, P=0.025) after adjustment for LVEF, hypertension, LVEDVi and LVMi. Conclusion: Multi-parametric CMR provides a satisfactory noninvasive tool for estimation of myocardial fibrosis and ventricular remodeling in patients with AI, and BAV is an independent risk factor for myocardial fibrosis in patients with AI.


Assuntos
Miocárdio , Adulto , Meios de Contraste , Feminino , Fibrose , Gadolínio , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda
19.
Adv Exp Med Biol ; 1165: 17-36, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399959

RESUMO

With continuing damage, both the indigenous cells of the cortex and medulla, and inflammatory cells are involved in the formation and development of renal fibrosis. Furthermore, interactions among the glomerular, tubular, and interstitial cells contribute to the process by excessive synthesis and decreased degradation of extracellular matrix. The morphology of kidney is different from pathological stages of diseases and changes with various causes. At the end stage of the disease, the kidneys are symmetrically contracted with diffuse granules. Most glomeruli show diffuse fibrosis and hyaline degeneration, and intervening tubules become atrophied. Renal interstitium shows obvious hyperplasia of fibrous tissues with marked infiltration of lymphocytes, mononuclear cells, and plasma cells. The renal arterioles are wall thickening frequently because of hyaline degeneration. Morphologic analysis based on Masson staining of the kidney tissues has been regarded as the golden standard to evaluate the visual fibrosis. However, the present studies have found that the evaluation system has poor repeatability. Several computer-aided image analysis techniques have been used to assess interstitial fibrosis. It is possible that the evaluation of renal fibrosis is carried out by the artificial intelligence renal biopsy pathological diagnosis system in the near future.


Assuntos
Nefropatias/patologia , Rim/patologia , Biópsia , Fibrose , Humanos , Glomérulos Renais/patologia
20.
Adv Exp Med Biol ; 1165: 37-47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399960

RESUMO

Arterial hypertension remains to be a serious problem with considerable morbidity and mortality worldwide in the present age. Hypertension is a major risk factor for cardiovascular diseases such as stroke, myocardial infarction, renal failure, and heart failure. Hypertensive nephropathy is the second leading cause of death in chronic kidney disease (CKD) around the world. Long-time hypertension loading results in renal interstitial fibrosis, which is associated with aberrant activation of renal fibroblasts and excessive generation of extracellular matrix (ECM) proteins. Increasing evidence supported that proteinuria, tubular hypertrophy, oxidative stress, activation of renin-aldosterone-angiotensin system (RAAS), collagen turnover, chronic inflammation, and vasoactive substances synergistically contributed to the pathogenesis of hypertensive renal fibrosis. However, the mechanisms involving the pathogenesis of hypertensive renal fibrosis are complex and not fully understood. Also, the effective clinical therapy to halt or even reverse renal fibrosis in hypertension is still limited. In this chapter, we aimed to provide an overview of the main pathophysiologic and mechanistic features of renal fibrosis under hypertensive state. The completion of the studies in these directions would improve our understanding of renal fibrosis in hypertension and also help us better screen treatment strategies for preventing renal destruction associated with hypertension.


Assuntos
Hipertensão/complicações , Nefropatias/complicações , Fibrose , Humanos , Hipertrofia , Rim/patologia , Estresse Oxidativo , Proteinúria , Sistema Renina-Angiotensina
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