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1.
Medicine (Baltimore) ; 99(15): e19682, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282722

RESUMO

BACKGROUND: Diabetic macroangiopathy is a further complication of diabetes mellitus and is the leading cause of death for diabetic patients. Shenqi compound (SC) is a traditional Chinese medicine formula widely used in the treatment of diabetes and diabetic macroangiopathy. At present, there is only 1 systematic review on SC in the treatment of diabetes. However, no meta-analysis has evaluated the efficacy and safety of SC on diabetic macroangiopathy. METHODS AND ANALYSIS: Three English database and four Chinese medical databases will be searched from its inception to February 2020. Then 2 methodological trained researchers will screen the qualified articles by reading the title, abstract, and full texts according to an established inclusion and exclusion criteria. The assessment of risk of bias will be conducted by using the Cochrane collaboration's tool. We will conduct meta-analyses for fasting blood glucose (FBG), postprandial blood glucose (PBG), glycated hemoglobin (HbA1c), and other outcomes. The heterogeneity of data will be evaluated by Cochrane χ and I tests. We establish 3 hypotheses before the subgroup analysis actually starts: disease status at baseline, duration of intervention, type of concomitant medication. We will conduct sensitivity analysis to evaluate the stability of the results, funnel plot analysis, and Egger test to evaluate the publication bias, and assessment for the quality of evidence by the Grading of Recommendations Assessment, Development, and Evaluate system (GRADE). RESULTS: The results will be published at a peer-reviewed journal. CONCLUSION: In this study, we will systematically evaluate the evidence of SC in the treatment of diabetic macroangiopathy. Our research is supposed to provide evidence-based support for clinical practice.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Medicamentos de Ervas Chinesas/administração & dosagem , Jejum/sangue , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Masculino , Medicina Tradicional Chinesa , Período Pós-Prandial/efeitos dos fármacos , Estudos Prospectivos , Projetos de Pesquisa , Sensibilidade e Especificidade , Doenças Vasculares/etiologia , Doenças Vasculares/patologia
2.
Am J Pathol ; 190(4): 742-751, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32035881

RESUMO

The endothelial glycocalyx is a vital regulator of vascular permeability. Damage to this delicate layer can result in increased protein and water transit. The clinical importance of albuminuria as a predictor of kidney disease progression and vascular disease has driven research in this area. This review outlines how research to date has attempted to measure the contribution of the endothelial glycocalyx to vessel wall permeability. We discuss the evidence for the role of the endothelial glycocalyx in regulating permeability in discrete areas of the vasculature and highlight the inherent limitations of the data that have been produced to date. In particular, this review emphasizes the difficulties in interpreting urinary albumin levels in early disease models. In addition, the research that supports the view that glycocalyx damage is a key pathologic step in a diverse array of clinical conditions, including diabetic complications, sepsis, preeclampsia, and atherosclerosis, is summarized. Finally, novel methods are discussed, including an ex vivo glomerular permeability assay that enhances the understanding of permeability changes in disease.


Assuntos
Permeabilidade Capilar , Endotélio Vascular/metabolismo , Glicocálix/fisiologia , Doenças Vasculares/patologia , Animais , Humanos , Doenças Vasculares/metabolismo
3.
Am J Pathol ; 190(4): 768-780, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32035885

RESUMO

Hyaluronan (HA) is a ubiquitous glycosaminoglycan of the extracellular matrix. It is present in the endothelial glycocalyx covering the apical surface of endothelial cells. The endothelial glycocalyx regulates blood vessel permeability and homeostasis. HA plays a central role in numerous functions of the endothelial surface layer, protecting the endothelial cells, regulating the barrier permeability, and ensuring mechanosensing, which is essential to nitric oxide production and flow-induced vasodilation. During acute injury, inflammatory conditions, or many other pathologic conditions, the endothelial glycocalyx is damaged, and its degradation is accompanied by shedding of one or more glycocalyx components into the blood. Syndecan-1, heparan sulfate, and HA are the main components whose shedding has been claimed to represent the endothelial glycocalyx state of health. This review focuses on endothelial glycocalyx HA and highlights its key roles in the functions of the endothelial glycocalyx, its shedding in several pathologic conditions such as sepsis, diabetes, chronic and acute kidney injury, ischemia/reperfusion, atherosclerosis, and inflammation, which are all accompanied by increased circulating HA levels. Plasma/serum HA level is becoming recognized as a biomarker of endothelial glycocalyx damage in select pathologies. Hyaluronidase, the main HA-degrading enzyme, and its involvement in the impairment of endothelial glycocalyx are also addressed.


Assuntos
Biomarcadores/metabolismo , Permeabilidade Capilar , Endotélio Vascular/patologia , Glicocálix/patologia , Ácido Hialurônico/metabolismo , Doenças Vasculares/patologia , Animais , Endotélio Vascular/metabolismo , Glicocálix/metabolismo , Humanos , Doenças Vasculares/metabolismo
4.
PLoS One ; 15(1): e0226681, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31971937

RESUMO

BACKGROUND: Splenic artery aneurysm (SAA) is a rare but potentially fatal condition. Rupture results in 25% mortality up to 75% in pregnant women with 95% fetal mortality. Brief reports suggest an increased risk of developing SAA in patients with HHT. METHODS: We analyzed enhanced multidetector CT data in 186 HHT patients matched (gender and ± 5 year old) with 186 controls. We screened for SAA and recorded diameter of splenic and hepatic arteries and hepatic, pancreatic and splenic parenchymal involvements. We determined by univariate and multivariate analysis, the relationship with age, sex, genetic status, cardiovascular risk factors (CVRF) and visceral involvement. RESULTS: SAA concerned 24.7% of HHT patients and 5.4% of controls, p<0.001. Factors associated with increased risk of SAA in HHT were female gender (p = 0.04, OR = 2.12, IC 95% = 1.03-4.50), age (p = 0.0003, OR = 1.04, 95% CI = 1.02-1.06) and pancreatic parenchymal involvement (p = 0.04, OR = 2.13, 95% CI = 1.01-4.49), but not type of mutation, hepatic or splenic parenchymal involvements, splenic size or splenic artery diameter or CVRF. CONCLUSIONS: We found a 4.57 higher rate of SAA in HHT patients without evidence of splenic high output related disease or increased CVRF. These results suggest the presence of a vascular intrinsic involvement. It should lead to screening all HHT patients for SAA. The vasculopathy hypothesis could require a change in management as screening of all systemic arteries and even the aorta and to further research in the field.


Assuntos
Aneurisma/epidemiologia , Artéria Esplênica/patologia , Telangiectasia Hemorrágica Hereditária/complicações , Doenças Vasculares/epidemiologia , Adulto , Idoso , Aneurisma/diagnóstico por imagem , Aneurisma/etiologia , Aneurisma/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/etiologia , Doenças Vasculares/patologia
5.
World Neurosurg ; 134: 79-85, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31669242

RESUMO

BACKGROUND: Segmental arterial mediolysis (SAM) is a rare non-atherosclerotic, noninflammatory vascular disease, characterized by mediolysis. We report an extremely rare case of subarachnoid hemorrhage (SAH) due to a ruptured blood blister-like aneurysm (BBA) of the internal carotid artery associated with SAM-related arteriopathy. CASE DESCRIPTION: We experienced a case of SAH followed by intraperitoneal hemorrhage that occurred 12 days after the SAH onset. SAH was caused by a ruptured BBA of the internal carotid artery, which was treated by trapping with high-flow bypass. Intraperitoneal hemorrhage was caused by a rupture of a posterior inferior pancreaticoduodenal artery (PIPDA) aneurysm, which induced hypovolemic shock resulting in death in spite of endovascular internal trapping. Postmortem pathologic examination revealed that the PIPDA pseudoaneurysm was due to SAM. CONCLUSIONS: We should pay attention to the association of SAM, which is a potentially life-threatening pathology when treating cerebral BBAs.


Assuntos
Aneurisma Roto/patologia , Artéria Carótida Interna/patologia , Artéria Mesentérica Superior/patologia , Túnica Média/patologia , Doenças Vasculares/patologia , Aneurisma Dissecante/etiologia , Aneurisma Dissecante/patologia , Aneurisma Roto/etiologia , Hemorragia/etiologia , Hemorragia/patologia , Humanos , Aneurisma Intracraniano/etiologia , Aneurisma Intracraniano/patologia , Masculino , Pessoa de Meia-Idade , Doenças Vasculares/complicações
6.
Stroke ; 51(1): 300-307, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31805844

RESUMO

Background and Purpose- Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an autosomal dominant small vessel disease caused by C-terminal frameshift mutations in the TREX1 gene that encodes the major mammalian 3' to 5' DNA exonuclease. RVCL-S is characterized by vasculopathy, especially in densely vascularized organs, progressive retinopathy, cerebral microvascular disease, white matter lesions, and migraine, but the underlying mechanisms are unknown. Methods- Homozygous transgenic RVCL-S knock-in mice expressing a truncated Trex1 (three prime repair exonuclease 1) protein (similar to what is seen in patients) and wild-type littermates, of various age groups, were subjected to (1) a survival analysis, (2) in vivo postocclusive reactive hyperemia and ex vivo Mulvany myograph studies to characterize the microvascular and macrovascular reactivity, and (3) experimental stroke after transient middle cerebral artery occlusion with neurological deficit assessment. Results- The mutant mice show increased mortality starting at midlife (P=0.03 with hazard ratio, 3.14 [95% CI, 1.05-9.39]). The mutants also show a vascular phenotype as evidenced by attenuated postocclusive reactive hyperemia responses (across all age groups; F[1, 65]=5.7, P=0.02) and lower acetylcholine-induced relaxations in aortae (in 20- to 24-month-old mice; RVCL-S knock-in: Emax: 37±8% versus WT: Emax: 65±6%, P=0.01). A vascular phenotype is also suggested by the increased infarct volume seen in 12- to 14-month-old mutant mice at 24 hours after infarct onset (RVCL-S knock-in: 75.4±2.7 mm3 versus WT: 52.9±5.6 mm3, P=0.01). Conclusions- Homozygous RVCL-S knock-in mice show increased mortality, signs of abnormal vascular function, and increased sensitivity to experimental stroke and can be instrumental to investigate the pathology seen in patients with RVCL-S.


Assuntos
Exodesoxirribonucleases , Leucoencefalopatias , Fosfoproteínas , Doenças Retinianas , Doenças Vasculares , Animais , Modelos Animais de Doenças , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , Técnicas de Introdução de Genes , Humanos , Leucoencefalopatias/enzimologia , Leucoencefalopatias/genética , Leucoencefalopatias/patologia , Camundongos , Camundongos Mutantes , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Doenças Retinianas/enzimologia , Doenças Retinianas/genética , Doenças Retinianas/patologia , Doenças Vasculares/enzimologia , Doenças Vasculares/genética , Doenças Vasculares/patologia
7.
Arterioscler Thromb Vasc Biol ; 40(2): 394-403, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31852223

RESUMO

OBJECTIVE: Pathological vascular remodeling and excessive perivascular fibrosis are major contributors to reduced vessel compliance that exacerbates cardiovascular diseases, for instance, promoting clinically relevant myocardial remodeling. Inflammation plays a significant role in both pathological vascular remodeling and fibrosis. We previously demonstrated that smooth muscle cell-specific PTEN depletion promotes significant vascular fibrosis and accumulation of inflammatory cells. In the current study, we aimed to determine the beneficial role of systemic PTEN elevation on Ang II (angiotensin II)-induced vascular fibrosis and remodeling. Approach and Results: Transgenic mice carrying additional copies of the wild-type Pten gene (super PTEN [sPTEN]) and WT littermates were subjected to Ang II or saline infusion for 14 or 28 days. Compared with WT, Ang II-induced vascular fibrosis was significantly blunted in sPTEN mice, as shown by histochemical stainings and label-free second harmonic generation imaging. The protection against Ang II was recapitulated in sPTEN mice bearing WT bone marrow but not in WT mice reconstituted with sPTEN bone marrow. Ang II-induced elevation of profibrotic and proinflammatory gene expression observed in WT mice was blocked in aortic tissue of sPTEN mice. Immunofluorescent staining and flow cytometry both indicated that perivascular infiltration of T cells and macrophages was significantly inhibited in sPTEN mice. In vitro induction of PTEN expression suppressed Ang II-induced Ccl2 expression in vascular smooth muscle cells. CONCLUSIONS: Systemic PTEN elevation mediates protection against Ang II-induced vascular inflammation and fibrosis predominantly through effects in resident vascular cells. Our data highly support that pharmacological upregulation of PTEN could be a novel and viable approach for the treatment of pathological vascular fibrosis.


Assuntos
Regulação da Expressão Gênica , Músculo Liso Vascular/metabolismo , PTEN Fosfo-Hidrolase/genética , Doenças Vasculares/genética , Remodelação Vascular/genética , Angiotensina II/toxicidade , Animais , Western Blotting , Células Cultivadas , Modelos Animais de Doenças , Fibrose/genética , Fibrose/metabolismo , Fibrose/patologia , Citometria de Fluxo , Masculino , Camundongos , Camundongos Transgênicos , Músculo Liso Vascular/patologia , PTEN Fosfo-Hidrolase/biossíntese , RNA/genética , Ratos , Doenças Vasculares/metabolismo , Doenças Vasculares/patologia
8.
Ren Fail ; 42(1): 19-29, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31858861

RESUMO

Renal microvascular lesions, common in lupus nephritis (LN), are associated with long-term poor outcomes. There are mainly five pathological types of renal microvascular lesions in LN: (1) vascular immune complex deposits (ICD), (2) arteriosclerosis (AS), (3) thrombotic microangiopathy (TMA), (4) non-inflammatory necrotizing vasculopathy (NNV), and (5) true renal vasculitis (TRV). The pathogenesis of renal microvascular lesions in LN remains to be elucidated. The activation and dysfunction of endothelial cells, in addition to the contribution of immune system dysfunction, especially the immune complex-induced vascular inflammation and antiphospholipid antibody-associated thrombotic events, are key mechanisms in the development of vascular lesions in LN that need to be further investigated. Alteration of the microvascular environment produces an acute immunological response that recruits immune cells, such as T cells, monocytes, and macrophages, which induces platelet aggregation with microthrombus formation. There is also increased cytotoxicity caused by cytokines produced by immune cells in the kidney. Identifying the mechanism underlying the pathogenesis of renal microvascular lesions in LN might provide potential targets for the development of novel therapies.


Assuntos
Rim/irrigação sanguínea , Nefrite Lúpica/complicações , Doenças Vasculares/imunologia , Células Endoteliais/imunologia , Células Endoteliais/patologia , Endotélio Vascular/citologia , Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Humanos , Rim/imunologia , Nefrite Lúpica/imunologia , Microvasos/imunologia , Microvasos/patologia , Literatura de Revisão como Assunto , Doenças Vasculares/patologia
9.
Am J Pathol ; 190(3): 520-534, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31866347

RESUMO

The adventitia, the outer layer of the blood vessel wall, may be the most complex layer of the wall and may be the master regulator of wall physiology and pathobiology. This review proposes a major shift in thinking to apply a functional lens to the adventitia rather than only a structural lens. Human and experimental in vivo and in vitro studies show that the adventitia is a dynamic microenvironment in which adventitial and perivascular adipose tissue cells initiate and regulate important vascular functions in disease, especially intimal hyperplasia and atherosclerosis. Although well away from the blood-wall interface, where much pathology has been identified, the adventitia has a profound influence on the population of intimal and medial endothelial, macrophage, and smooth muscle cell function. Vascular injury and dysfunction of the perivascular adipose tissue promote expansion of the vasa vasorum, activation of fibroblasts, and differentiation of myofibroblasts. This regulates further biologic processes, including fibroblast and myofibroblast migration and proliferation, inflammation, immunity, stem cell activation and regulation, extracellular matrix remodeling, and angiogenesis. A debate exists as to whether the adventitia initiates disease or is just an important participant. We describe a mechanistic model of adventitial function that brings together current knowledge and guides the design of future investigations to test specific hypotheses on adventitial pathobiology.


Assuntos
Aterosclerose/patologia , Hiperplasia/patologia , Doenças Vasculares/patologia , Tecido Adiposo/patologia , Túnica Adventícia/patologia , Matriz Extracelular/patologia , Fibroblastos/patologia , Humanos , Inflamação/patologia , Macrófagos/patologia , Modelos Biológicos , Miócitos de Músculo Liso/patologia , Miofibroblastos/patologia , Células-Tronco/fisiologia , Vasa Vasorum/patologia
10.
Oxid Med Cell Longev ; 2019: 4851323, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827677

RESUMO

Glycation, oxidation, nitration, and crosslinking of proteins are implicated in the pathogenic mechanisms of type 2 diabetes, cardiovascular disease, and chronic kidney disease. Related modified amino acids formed by proteolysis are excreted in urine. We quantified urinary levels of these metabolites and branched-chain amino acids (BCAAs) in healthy subjects and assessed changes in early-stage decline in metabolic, vascular, and renal health and explored their diagnostic utility for a noninvasive health screen. We recruited 200 human subjects with early-stage health decline and healthy controls. Urinary amino acid metabolites were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. Machine learning was applied to optimise and validate algorithms to discriminate between study groups for potential diagnostic utility. Urinary analyte changes were as follows: impaired metabolic health-increased N ε -carboxymethyl-lysine, glucosepane, glutamic semialdehyde, and pyrraline; impaired vascular health-increased glucosepane; and impaired renal health-increased BCAAs and decreased N ε -(γ-glutamyl)lysine. Algorithms combining subject age, BMI, and BCAAs discriminated between healthy controls and impaired metabolic, vascular, and renal health study groups with accuracy of 84%, 72%, and 90%, respectively. In 2-step analysis, algorithms combining subject age, BMI, and urinary N ε -fructosyl-lysine and valine discriminated between healthy controls and impaired health (any type), accuracy of 78%, and then between types of health impairment with accuracy of 69%-78% (cf. random selection 33%). From likelihood ratios, this provided small, moderate, and conclusive evidence of early-stage cardiovascular, metabolic, and renal disease with diagnostic odds ratios of 6 - 7, 26 - 28, and 34 - 79, respectively. We conclude that measurement of urinary glycated, oxidized, crosslinked, and branched-chain amino acids provides the basis for a noninvasive health screen for early-stage health decline in metabolic, vascular, and renal health.


Assuntos
Biomarcadores/urina , Rim/metabolismo , Doenças Metabólicas/patologia , Doenças Vasculares/patologia , Adulto , Algoritmos , Aminoácidos de Cadeia Ramificada/metabolismo , Aminoácidos de Cadeia Ramificada/urina , Índice de Massa Corporal , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Produtos Finais de Glicação Avançada/urina , Glicosilação , Humanos , Lisina/análogos & derivados , Lisina/urina , Masculino , Doenças Metabólicas/metabolismo , Oxirredução , Índice de Gravidade de Doença , Espectrometria de Massas em Tandem , Tirosina/análogos & derivados , Tirosina/urina , Doenças Vasculares/metabolismo
11.
Rev Med Suisse ; 15(674): 2236-2240, 2019 Dec 04.
Artigo em Francês | MEDLINE | ID: mdl-31804035

RESUMO

Lower extremity arterial disease (LEAD) is a serious and invalidating disease with a relatively high prevalence in the diabetic population. Patients suffering from both conditions have a less favourable prognosis of affected limbs compared to non-diabetic patients, with more frequent adverse limb events such as amputations. Nevertheless, awareness of LEAD remains sub-optimal in the diabetic population. Regular and appropriate screening for this condition is therefore recommended. Affected individuals should receive optimal medical treatment, including intensive management of the various cardiovascular risk factors and strict blood glucose control.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Extremidade Inferior/irrigação sanguínea , Doenças Vasculares/complicações , Doenças Vasculares/diagnóstico , Amputação , Artérias/patologia , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/terapia , Humanos , Fatores de Risco , Doenças Vasculares/patologia , Doenças Vasculares/terapia
12.
Rev Med Suisse ; 15(674): 2242-2246, 2019 Dec 04.
Artigo em Francês | MEDLINE | ID: mdl-31804036

RESUMO

Prevalence of lower extremity artery disease (LEAD) is increasing with age, and there is a trend over the last decade towards an increase of LEAD patients. These patients are at increased risk of lower limb adverse event (MALE), but also at very high risk of major cardiovascular events (MACE). The best medical treatment, including medications, enable a reduction of this risk. Nevertheless, some patients will continue to develop MACE. New therapeutic molecules have been developed with randomized controlled trials, and showed a reduction of the -cardiovascular risk among these selected patients.


Assuntos
Artérias/patologia , Extremidade Inferior/irrigação sanguínea , Doenças Vasculares/terapia , Humanos , Fatores de Risco , Resultado do Tratamento , Doenças Vasculares/patologia
13.
PLoS One ; 14(12): e0225911, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31805124

RESUMO

Collagen accumulation and remodeling in the vascular wall is a cardinal feature of vascular fibrosis that exacerbates the complications of hypertension, aging, diabetes and atherosclerosis. With no specific therapy available to date, identification of mechanisms underlying vascular fibrogenesis is an important clinical goal. Here, we tested the hypothesis that Discoidin Domain Receptor 2 (DDR2), a collagen-specific receptor tyrosine kinase, is a determinant of arterial fibrosis. We report a significant increase in collagen type 1 levels along with collagen and ECM remodeling, degradation of elastic laminae, enhanced fat deposition and calcification in the abdominal aorta in a non-human primate model of high-fat, high-sucrose diet (HFS)-induced metabolic syndrome. These changes were associated with a marked increase in DDR2. Resveratrol attenuated collagen type I deposition and remodeling induced by the HFS diet, with a concomintant reduction in DDR2. Further, in isolated rat vascular adventitial fibroblasts and VSMCs, hyperglycemia increased DDR2 and collagen type I expression via TGF-ß1/SMAD2/3, which was attenuated by resveratrol. Notably, gene knockdown and overexpression approaches demonstrated an obligate role for DDR2 in hyperglycemia-induced increase in collagen type I expression in these cells. Together, our observations point to DDR2 as a hitherto unrecognized molecular link between metabolic syndrome and arterial fibrosis, and hence a therapeutic target.


Assuntos
Artérias/metabolismo , Artérias/patologia , Receptor com Domínio Discoidina 2/genética , Síndrome Metabólica/complicações , Síndrome Metabólica/genética , Doenças Vasculares/etiologia , Doenças Vasculares/patologia , Animais , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Receptor com Domínio Discoidina 2/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Fibroblastos/metabolismo , Fibrose , Masculino , Síndrome Metabólica/metabolismo , Primatas
14.
Reumatol. clín. (Barc.) ; 15(6): 368-369, nov.-dic. 2019. ilus
Artigo em Espanhol | IBECS | ID: ibc-189661

RESUMO

Paciente masculino de 56 años con poliangitis microscópica y polineuropatía periférica simétrica de extremidades con p-ANCA positivo, patrón EMG de mononeuritis múltiple y biopsia cutánea con vasculitis inespecífica, quien presentaba flebectasia con plétora y trayectos tortuosos en el dorso de los dedos en ambas manos, paresia e hipoestesia digital en manos y pies con limitación funcional. Mediante la administración de prednisona, azatioprina y pulso de ciclofosfamida, mejoró rápidamente de los síntomas generales pero muy lentamente de la neuropatía. Después de 47 meses de evolución persiste discreta flebectasia digital en manos y ligera hipoestesia en manos y pies, con parámetros de laboratorio normales. La flebectasia, probablemente, fue el resultado de una disautonomía por vasculitis de la vasa nervorum y podría ser un signo a ratificar en casos semejantes


The patient was a 56-year-old man with microscopic polyangiitis and symmetrical peripheral polyneuropathy of the extremities who was positive for p-ANCA, EMG pattern of mononeuritis multiplex and skin biopsy showing the presence of nonspecific vasculitis. He had phlebectasia with plethora and tortuous vessels on dorsum of the fingers on both hands, paresis and hypoesthesia of fingers and toes with functional limitations. The administration of prednisone, azathioprine and a cyclophosphamide pulse achieved rapid improvement in the general symptoms, but the changes in the neuropathy occurred very slowly. After 47 months of treatment, he had mild phlebectasia in fingers and slight hypoesthesia in hands and feet, with normal laboratory tests. Phlebectasia was probably the result of an autonomic dysfunction due to vasculitis of the vasa nervorum and could be a sign to look for in similar cases


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Dedos/irrigação sanguínea , Poliangiite Microscópica/complicações , Doenças do Sistema Nervoso Periférico/complicações , Polineuropatias/complicações , Doenças Vasculares/etiologia , Veias/patologia , Dilatação Patológica/etiologia , Doenças Vasculares/patologia
15.
Nat Genet ; 51(11): 1574-1579, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31676865

RESUMO

Venous thromboembolism is a significant cause of mortality1, yet its genetic determinants are incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank, with testing of approximately 13 million DNA sequence variants for association with venous thromboembolism (26,066 cases and 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 venous thromboembolism cases and 167,295 controls. We identified 22 previously unknown loci, bringing the total number of venous thromboembolism-associated loci to 33, and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for venous thromboembolism that identifies 5% of the population at an equivalent incident venous thromboembolism risk to carriers of the established factor V Leiden p.R506Q and prothrombin G20210A mutations. Our data provide mechanistic insights into the genetic epidemiology of venous thromboembolism and suggest a greater overlap among venous and arterial cardiovascular disease than previously thought.


Assuntos
Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Doenças Vasculares/genética , Tromboembolia Venosa/genética , Idoso , Animais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/genética , Fatores de Risco , Reino Unido/epidemiologia , Doenças Vasculares/epidemiologia , Doenças Vasculares/patologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/patologia
16.
Kathmandu Univ Med J (KUMJ) ; 17(65): 30-34, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31734675

RESUMO

Background Extra hepatic portal vein obstruction (EHPVO) is a common cause of portal hypertension in the developing countries (up to 30% of all variceal bleeders) and is second to cirrhosis in the West (up to 5-10%). Our understanding of the disease is poor compared with other illnesses. Objective To undertake a retrospective study of the clinicoepidemiological profile of Extra hepatic portal vein obstruction in a tertiary care hospital in eastern Nepal. Method All consecutive adult patients whose features were consistent with the diagnosis of extra hepatic portal vein obstruction from June 2014 to June 2016 were retrospectively analyzed to explore the various clinico-epidemiological parameters. Result A total of 58 patients were enrolled in the study with a median age of 24 years (20.5- 40). Portal vein thrombosis was the most common cause of extrahepatic portal vein obstruction. Hematemesis followed by melena were the most common presenting symptoms. All patients had splenomegaly on examination. None of the patients had clinical, biochemical or radiological evidence of chronic liver disease. Conclusion The diagnosis of extra hepatic portal venous obstruction and differentiation from cirrhosis can be easily made by characteristic clinical features, normal liver function tests and doppler ultrasound. Portal vein thrombosis (PVT) is the predominant cause of extra hepatic portal vein obstruction in Nepali patients, as seen at this tertiary care hospital in Nepal.


Assuntos
Veia Porta/patologia , Doenças Vasculares/patologia , Trombose Venosa/etiologia , Adulto , Feminino , Humanos , Hipertensão Portal/etiologia , Fígado/irrigação sanguínea , Cirrose Hepática , Masculino , Melena , Nepal , Estudos Retrospectivos , Esplenomegalia , Centros de Atenção Terciária , Doenças Vasculares/complicações , Doenças Vasculares/epidemiologia , Doenças Vasculares/etiologia , Adulto Jovem
18.
PLoS One ; 14(10): e0223944, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31647843

RESUMO

AIM: To evaluate the safety of 1.25mg and 2mg intravitreal ziv-aflibercept (IVZ) in Ghanaian eyes with choroido-retinal vascular diseases. DESIGN: Prospective, randomised, double blind, interventional study. METHODS: Twenty patients with centre involving macular oedema in diabetic retinopathy, retinal vein occlusion, and neovascular age-related macular degeneration were assigned to 2 groups receiving 3 doses of 1.25mg/0.05ml (group 1) and 2mg/0.08ml IVZ (Group 2) at 4 weekly intervals. Safety data was collected after 30 minutes, 1 and 7 days, and 4, 8 and 12 weeks after injection. Changes in continuous variables were compared using paired t-test and categorical variables were compared using chi-square test of proportions. Repeated-Measures ANOVA with nesting test was used to compare variations in continuous variables by IVZ dose over time. Primary outcome measures were ocular and systemic adverse events at 4 weeks. RESULTS: Eleven females and nine males, with mean age of 63.2± 7.3 years were included. Ocular adverse events included subconjunctival haemorrhage in 1 eye, intraocular pressure (IOP) >21mmHg at 30 minutes in 6 eyes and mild pain in 3 eyes at 1-day. There was no significant difference in IOP rise between the 2 groups at 30 minutes (p = 0.21). No other ocular or systemic adverse events were observed. There was significant improvement in the best corrected visual acuity (LogMAR) from 0.95±0.6 to 0.6±0.4 (p<0.01) and 0.47±0.3 (p<0.01), reduction in central subfield foveal thickness from 405.9±140 um at baseline to 255.6±75 um (p<0.01) and 238±88 um (p<0.01) at 4 and 12 weeks respectively, although no difference was observed between the 2 groups (p = 0.34). CONCLUSION: IVZ at 1.25mg and 2mg had similar safety profiles, and did not have any major unexpected adverse events. Further studies with larger cohorts are required to confirm efficacy.


Assuntos
Plexo Corióideo/patologia , Edema Macular/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Doenças Retinianas/tratamento farmacológico , Doenças Vasculares/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Injeções Intravítreas , Edema Macular/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Doenças Retinianas/patologia , Doenças Vasculares/patologia
19.
Pediatr Rheumatol Online J ; 17(1): 69, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651352

RESUMO

BACKGROUND/PURPOSE: Endothelium is a key element in the regulation of vascular homeostasis and its alteration can lead to the development of vascular diseases. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with potential extensive vascular lesions, involving skin vessels, renal glomeruli, cardiovascular system, brain, lung alveoli, gastrointestinal tract vessels and more. We aimed to assess endothelial dysregulation related biomarkers in pediatric-onset SLE (pSLE) patient serum and elucidate its correlation with their clinical features, laboratory parameters, and the overall disease activity. METHODS: Disease activities were evaluated by SLE disease activity index (SLEDAI). Patient characteristics were obtained by retrospective chart review. Six biomarkers associated with endothelial dysregulation, including Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Tie2, Vascular endothelial growth factor (VEGF), thrombomodulin, and a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13) were tested through enzyme-linked immunosorbent assay (ELISA) measurement. RESULTS: This study comprised 118 pSLE patients. Data from 40 age-matched healthy controls were also obtained. The mean diagnostic age was 13 ± 4.12 years-old and 90.7% are females. Serum levels of VEGF, Tie2, thrombomodulin were significantly higher while serum ADAMTS13 was lower in active pSLE patients when compared to those with inactive diseases (all p < 0.05). In organ specific association, serum thrombomodulin level was higher in pSLE patient with renal involvement, and serum ADAMTS13 levels was negatively associated with neurological involvement (p < 0.05). A cutoff of thrombomodulin at 3333.6 pg/ml best correlated renal involvement. (AUC = 0.752, p < 0.01). CONCLUSION: Endothelial dysregulation associating proteins seems to be potent biomarkers for pSLE activity as well as organ involvement in pSLE patients. These biomarkers may be beneficial in understanding of the vascular pathogenesis and disease monitoring.


Assuntos
Endotélio Vascular/patologia , Lúpus Eritematoso Sistêmico/patologia , Proteína ADAMTS13/sangue , Adolescente , Angiopoietina-1/sangue , Angiopoietina-2/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Receptor TIE-2/sangue , Trombomodulina/sangue , Doenças Vasculares/sangue , Doenças Vasculares/patologia , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
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