O Lupus Eritematoso Sistemico (LES) e um disturbio autoimune, multissistemico, de etiologia ainda nao bem esclarecida. E uma doenca rara, com a incidencia de 8,7 a cada 100.000 habitantes da populacao brasileira em geral e, frequentemente, em mulheres jovens durante a fase reprodutiva. A disfuncao imune presente no LES leva a grande producao de autoanticorpos e imunocomplexos, ativacao excessiva do complemento e a um processo inflamatorio tecidual insidioso. Dentre as diversas manifestacoes do LES, a nefrite lupica (NL) e a mais relevante ocorrendo em ate 50% dos pacientes no momento do diagnostico, e em ate 60% dos pacientes durante o curso da doenca. A patogenese da doenca e extremamente complexa, com diversos estudos evidenciando alteracoes nos fenotipos linfocitarios. O objetivo deste estudo foi determinar as alteracoes do sistema imune de pacientes com LES em tratamento, e comparar estas alteracoes nas formas inativa e ativa da doenca entre si, e com o grupo controle. Participaram deste estudo um total de 30 pacientes com LES e, como controle, 11 individuos sem a doenca (CN). Foram avaliados os marcadores de celulas NK, T e B tais como CD3, CD4, CD8, CD16, CD19, CD25, CD56, HLA-DR, NKG2D e FoxP3 em linfocitos do sangue periferico por meio da tecnica de citometria de fluxo. A populacao de celulas NKt se mostrou diminuida apenas em pacientes com a forma ativa da doenca, enquanto as populacoes de celulas efetoras T CD4+, T reguladoras FoxP3+ e de celulas B se mostraram diminuidas em pacientes com LES, em ambas as formas ativa e inativa, quando comparado ao grupo controle. Ao contrario, a populacao de celulas T CD8 se mostrou elevada no grupo com LES, nas formas ativa e inativa. Foi tambem observado um aumento na expressao do marcador de atividade NKG2D em celulas CD3+CD56- em pacientes com nefrite em relacao aos nao portadores, enquanto as populacoes de celulas efetoras T CD4+ e de celulas B se mostraram diminuidas em pacientes com NL quando comparadas ao grupo controle. Ao contrario, a populacao de celulas T CD8+ se mostrou elevada no grupo com LES com ou sem NL. Quanto aos principais medicamentos utilizados pelos pacientes com LES, o uso de azatioprina nao afetou os perfis de expressao das celulas T, B e NK; tampouco a dose de prednisona. Ao contrario, os usuarios de hidroxicloroquina apresentaram uma maior expressao dos marcadores de celulas NK em relacao aos nao usuarios. Apesar dos pacientes estudados estarem em tratamento, os dados em conjunto permitem confirmar disfuncao do sistema imune peculiar no LES, bem como variacoes do perfil fenotipico celular em funcao do status da doenca.
This paper aims to review the diagnosis, epidemiological data, etiology, pathophysiology and progression of Chronic Kidney Disease (CKD), with emphasis on pediatric patients. CKD is defined as a group of structural and functional kidney abnormalities observed for more than three months, which affects patient's health. CKD prevalence in children is lower than in adults, but is associated to cardiovascular diseases and has high mortality and morbidity rates. CKD-affected children have alterations in physical and psychological development, growth retardation and muscle weakness, among other complications which decrease patients’ quality of life. The main causes of CKD in children are congenital anomalies of the kidney and urinary tract, and primary glomerulopathy, especially focal segmental glomerulosclerosis. Some conditions contribute to CKD progression, such as responsiveness to treatment. The knowledge of the pathophysiology of CKD and disease progression mechanisms is important for the early treatment and to predict the clinical evolution, aiming to provide counseling to families and to slow the progression of kidney disease to an end stage.
Abstract The pathogenesis of systemic lupus erythematosus (SLE) is complex. Few studies in Brazilian population have addressed cell phenotypes associated with immunological responses and their associations with SLE activity. The aim of this study is to investigate cell phenotypes associated to SLE diagnosis, treatment and activity. Twenty-eight SLE female patients (17 inactive, 11 active) and 10 healthy women were included in this study. Markers of natural killer (Nk), T and B cells in peripheral blood were evaluated by flow cytometry. Nkt cells were decreased only in SLE active patients. Activated CD4+, regulatory T FoxP3+ and B cells were decreased in both active and inactive SLE patients, compared to control group. The data corroborate the disruption of immune regulatory response in SLE patients and suggest phenotipic changes as possible biomarkers of SLE activity.
In the last few years, microparticles (MPs) have been studied as new specialized structures for intercellular communication (Ratajczak et al., 2006; Pap et al., 2009). The MPs are small extracellular cell-derived vesicles, ranging in size from 0.1 to 1 μm, released by a diverse population of cells upon activation or apoptosis, particularly under conditions of stress or injury (Muralidharan-Chari et al., 2010; Saman et al., 2012). MPs are important messengers in cell-cell communication and contribute to the induction of endothelial damage, inflammation, and angiogenesis, carrying signaling molecules, such as chemokines, cytokines, enzymes, growth factors, receptors, adhesion molecules, mRNAs and microRNA (Marques et al. 2013). It has been demonstrated that MPs derived from platelets may carrier the amyloid precursor protein (APP) and the beta-amyloi protein (Aβ), besides to be associated to Alzheimer's Disease (AD) (Matsubara et al., 2002). 54 individuals were recruited and classified as probable AD (29 patients - 15 men and 14 women, age 72,9±7,0 years) and cognitively healthy individuals (25 controls - 8 men and 17 women, age 73,2±7,7 years). Blood samples were collected and MPs were isolated by ultracentrifugation and measured by flow cytometry. Statistical analyses were performed using Mann-Whitney test on SPSS program version 13.0. Values of p < 0.05 were considered significant. The median (interquartile range) levels of MPs (MPs/μL) derived from tissue factor [78.8 (82.2)], leukocytes [109.9 (86.9)], endothelium [40.9 (76.5)] and neuron [200.3 (362.4)] are significant higher in AD group than in control group [37.4 (13.4); 39.0 (27.3); 21.8 (20.8) and 41.4 (72.4), respectively; all p<0.05]. MPs derived from platelet did not differ between the groups [112.7 (257.1) for AD and 159.1 (143.1) for controls; p = 0.167]. The results suggest that MPs derived from tissue factor, leukocytes, endothelium and neuron could be associated with the physiopathology of AD. However, more studies are necessary to validate our findings and to establish the MPs as new biomarkers for AD diagnosis.
Alzheimer’s disease (AD) is the most common type of dementia and typically manifests through a progressive loss of episodic memory and cognitive function, subsequently causing language and visuospatial skills deficiencies, which are often accompanied by behavioral disorders such as apathy, aggressiveness and depression. The presence of extracellular plaques of insoluble β-amyloid peptide (Aβ) and neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein (P-tau) in the neuronal cytoplasm is a remarkable pathophysiological cause in patients’ brains. Approximately 70% of the risk of developing AD can be attributed to genetics. However, acquired factors such as cerebrovascular diseases, diabetes, hypertension, obesity and dyslipidemia increase the risk of AD development. The aim of the present minireview was to summarize the pathophysiological mechanism and the main risk factors for AD. As a complement, some protective factors associated with a lower risk of disease incidence, such as cognitive reserve, physical activity and diet will also be addressed.
Abstract Alzheimer's disease (AD) is considered the most frequent cause of dementia. It is known that vascular risk factors play an important role in the development and progression of this condition. Alterations in vascular walls represent documented findings in patients with AD and other dementias affecting elderly people. The authors performed a systematic review and meta-analysis, aiming to synthesize observational studies that evaluated how the hemostatic system may contribute to cognitive decline in the elderly, using papers published until April 2018 and as indexed in Medline (PubMed), Scopus, Web of Science, ScienceDirect, Lilacs, Cinahl, PsycINFO, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Among 5,278 studies identified, 32 were included in the final synthesis, and these included 485 patients with mild cognitive impairment, 568 with vascular dementia (VD), 1,781 with AD, and 2,855 participants without dementia. AD patients had increased plasma von Willebrand factor (VWF) (standardized mean difference [SMD]: 2.53; 95% confidence interval [CI]: 0.10–4.95), D-dimer (SMD: 0.50; 95% CI: 0.35–0.66), plasminogen activator inhibitor-1 (SMD: 3.34; 95% CI: 1.01–5.67), thrombomodulin (SMD: 1.08; 95% CI: 0.53–1.62), and homocysteine levels (SMD: 0.65; 95% CI: 0.15–1.15). In contrast, the VD group showed increased fibrinogen levels (SMD: 0.77; 95% CI: 0.13–1.41), activated factor VII (SMD: 0.36; 95% CI: 0.05–0.67), factor VIII (SMD: 0.57; 95% CI: 0.22–0.91), VWF (SMD: 2.34; 95% CI: 0.38–4.29), D-dimer (SMD: 1.14; 95% CI: 0.51–1.78), and homocysteine (SMD: 2.17; 95% CI: 1.67–2.68). AD showed an elevation in some markers of endothelial dysfunction, whereas VD presented mostly an involvement of coagulation cascade components.
Platelets play an important role in proinflammatory process in addition to haemostasis and share neuronal pathways that lead to synthesis of neurotransmitters and APP (amyloid precursor protein). Studies involving platelets have been of great interest, particularly with regard to platelet activation and its relation in the development of AD. P-selectin is an adhesion molecule that is expressed on the surface of platelet when it is activated. In the Brazilian population, few studies were conducted aiming to know more about platelet activity in patients with AD, Frontotemporal Dementia (FTD) and in elderly individuals without cognitive impairment. The aim of this study was to compare platelet activity in 23 AD patients diagnosed by cognitive tests and characterized by CSF biomarkers, including beta-amyloid protein (βA-42; <700 pg / mL), Tau-Total (> 400 pg / mL), phosphorylated Tau (P-Tau> 60 pg / mL) and IATI (<0.8), in 20 FTD patients and in 27 individuals without cognitive impairment according to clinical criteria (control group). P-selectin expression was evaluated by using CD62P and its quantification performed by flow cytometry. An increase in percentage of P-selectin expression was observed when comparing the AD and control groups (median = 3.42, Q1 = 1.50-Q3 = 7.56 versus 1.30, 0.34–2.82, p <0.0001), FTD and control groups (median = 2.27, Q1= 1.16-Q3= 6.74 versus1.30, 0.34–2.82; p= 0.025), but no difference was observed between DA and FTD (p= 0.318). P-selectin is involved in adhesion of platelets to endothelial cells and recruitment of leukocytes at sites of vascular lesions. P-selectin plays a fundamental role in inflammatory process and in development of micro thrombi, leading to worsening of local perfusion which may exacerbate neuroinflammation present in AD and cognitive decline. Regarding FTD, reports on platelet activity are scarce, however the increase in the expression of P-selectin compared to control group may be related to a neuroinflammatory process or dysfunction of microvasculature. In summary, platelets from AD and FTD patients presented an increased platelet activation reflecting a greater expression of P-selectin, compared to individuals without cognitive decline and of the same age group. Support: CNPq, CAPES and FAPEMIG.
'/%3e%3cpath id='l' d='M-26.25 0h52.5v-12h-40.5v-16h33v-12h-33v-11H25v-12h-51.25z'/%3e%3cpath id='k' d='M-31.5 0h12v-48l14 48h11l14-48V0h12v-70H14L0-22l-14-48h-17.5z'/%3e%3cpath id='b' fill-rule='evenodd' d='M0 0a31.5 35 0 0 0 0-70A31.5 35 0 0 0 0 0m0-13a18.5 22 0 0 0 0-44 18.5 22 0 0 0 0 44'/%3e%3cpath id='d' fill-rule='evenodd' d='M-31.5 0h13v-26h28a22 22 0 0 0 0-44h-40zm13-39h27a9 9 0 0 0 0-18h-27z'/%3e%3cpath id='n' d='M-15.75-22C-15.75-15-9-11.5 1-11.5s14.74-3.25 14.75-7.75c0-14.25-46.75-5.25-46.5-30.25C-30.5-71-6-70 3-70s26 4 25.75 21.25H13.5c0-7.5-7-10.25-15-10.25-7.75 0-13.25 1.25-13.25 8.5-.25 11.75 46.25 4 46.25 28.75C31.5-3.5 13.5 0 0 0c-11.5 0-31.55-4.5-31.5-22z'/%3e%3cuse xlink:href='%23a' id='o' transform='scale(31.5)'/%3e%3cuse xlink:href='%23a' id='p' transform='scale(26.25)'/%3e%3cuse xlink:href='%23a' id='r' transform='scale(21)'/%3e%3cuse xlink:href='%23a' id='q' transform='scale(15)'/%3e%3cuse xlink:href='%23a' id='s' transform='scale(10.5)'/%3e%3cg id='m'%3e%3cclipPath id='c'%3e%3cpath d='M-31.5 0v-70h63V0zM0-47v12h31.5v-12z'/%3e%3c/clipPath%3e%3cuse xlink:href='%23b' clip-path='url(%23c)'/%3e%3cpath d='M5-35h26.5v10H5z'/%3e%3cpath d='M21.5-35h10V0h-10z'/%3e%3c/g%3e%3cg id='h'%3e%3cuse xlink:href='%23d'/%3e%3cpath d='M28 0c0-10 0-32-15-32H-6c22 0 22 22 22 32'/%3e%3c/g%3e%3cg id='a' fill='%23fff'%3e%3cg id='f'%3e%3cpath id='e' d='M0-1v1h.5' transform='rotate(18 0 -1)'/%3e%3cuse xlink:href='%23e' transform='scale(-1 1)'/%3e%3c/g%3e%3cuse xlink:href='%23f' transform='rotate(72)'/%3e%3cuse xlink:href='%23f' transform='rotate(-72)'/%3e%3cuse xlink:href='%23f' transform='rotate(144)'/%3e%3cuse xlink:href='%23f' transform='rotate(216)'/%3e%3c/g%3e%3c/defs%3e%3crect width='100%25' height='100%25' x='-50%25' y='-50%25' fill='%23009b3a'/%3e%3cpath fill='%23fedf00' d='M-1743 0 0 1113 1743 0 0-1113z'/%3e%3ccircle r='735' fill='%23002776'/%3e%3cclipPath id='g'%3e%3ccircle r='735'/%3e%3c/clipPath%3e%3cpath fill='%23fff' d='M-2205 1470a1785 1785 0 0 1 3570 0h-105a1680 1680 0 1 0-3360 0z' clip-path='url(%23g)'/%3e%3cg fill='%23009b3a' transform='translate(-420 1470)'%3e%3cuse xlink:href='%23b' y='-1697.5' transform='rotate(-7)'/%3e%3cuse xlink:href='%23h' y='-1697.5' transform='rotate(-4)'/%3e%3cuse xlink:href='%23i' y='-1697.5' transform='rotate(-1)'/%3e%3cuse xlink:href='%23j' y='-1697.5' transform='rotate(2)'/%3e%3cuse xlink:href='%23k' y='-1697.5' transform='rotate(5)'/%3e%3cuse xlink:href='%23l' y='-1697.5' transform='rotate(9.75)'/%3e%3cuse xlink:href='%23d' y='-1697.5' transform='rotate(14.5)'/%3e%3cuse xlink:href='%23h' y='-1697.5' transform='rotate(17.5)'/%3e%3cuse xlink:href='%23b' y='-1697.5' transform='rotate(20.5)'/%3e%3cuse xlink:href='%23m' y='-1697.5' transform='rotate(23.5)'/%3e%3cuse xlink:href='%23h' y='-1697.5' transform='rotate(26.5)'/%3e%3cuse xlink:href='%23j' y='-1697.5' transform='rotate(29.5)'/%3e%3cuse xlink:href='%23n' y='-1697.5' transform='rotate(32.5)'/%3e%3cuse xlink:href='%23n' y='-1697.5' transform='rotate(35.5)'/%3e%3cuse xlink:href='%23b' y='-1697.5' transform='rotate(38.5)'/%3e%3c/g%3e%3cuse xlink:href='%23o' x='-600' y='-132'/%3e%3cuse xlink:href='%23o' x='-535' y='177'/%3e%3cuse xlink:href='%23p' x='-625' y='243'/%3e%3cuse xlink:href='%23q' x='-463' y='132'/%3e%3cuse xlink:href='%23p' x='-382' y='250'/%3e%3cuse xlink:href='%23r' x='-404' y='323'/%3e%3cuse xlink:href='%23o' x='228' y='-228'/%3e%3cuse xlink:href='%23o' x='515' y='258'/%3e%3cuse xlink:href='%23r' x='617' y='265'/%3e%3cuse xlink:href='%23p' x='545' y='323'/%3e%3cuse xlink:href='%23p' x='368' y='477'/%3e%3cuse xlink:href='%23r' x='367' y='551'/%3e%3cuse xlink:href='%23r' x='441' y='419'/%3e%3cuse xlink:href='%23p' x='500' y='382'/%3e%3cuse xlink:href='%23r' x='365' y='405'/%3e%3cuse xlink:href='%23p' x='-280' y='30'/%3e%3cuse xlink:href='%23r' x='200' y='-37'/%3e%3cuse xlink:href='%23o' y='330'/%3e%3cuse xlink:href='%23p' x='85' y='184'/%3e%3cuse xlink:href='%23p' y='118'/%3e%3cuse xlink:href='%23r' x='-74' y='184'/%3e%3cuse xlink:href='%23q' x='-37' y='235'/%3e%3cuse xlink:href='%23p' x='220' y='495'/%3e%3cuse xlink:href='%23r' x='283' y='430'/%3e%3cuse xlink:href='%23r' x='162' y='412'/%3e%3cuse xlink:href='%23o' x='-295' y='390'/%3e%3cuse xlink:href='%23s' y='575'/%3e%3c/svg%3e)