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INTRODUCTION: The management of even large pericardial effusions in asymptomatic patients is still a matter of debate. Aim of the present study is to explore, in a multicenter setting, the rate of post-cardiac injury syndromes (PCIS) and pericardial effusion recurrence after pericardial effusion drainage procedure. MATERIAL AND METHODS: This is a multicenter international retrospective study including a consecutive cohort of patients diagnosed with large, chronic and idiopathic pericardial effusions, prospectively evaluated from January 2003 to December 2021 who underwent a clinically indicated pericardial drainage procedure. Two separate end-points were recorded: 1) recurrence of pericardial effusion after drainage without any sign of pericardial inflammation 2) occurrence of PCIS, defined as the new onset of pericarditis 1 to 6 weeks after pericardial intervention. RESULTS: 124 patients were enrolled (50 % female, mean age 64 years old). A mean follow-up of 29.6 ± 25.6 months was obtained in 110 patients (88 %). 110 patients were treated with pericardiocentesis (89 %), 25 with pleuro-pericardial windows (20 %), and 1 with pericardiectomy (1 %). PCIS occurred in 21 out of 124 patients followed for at least 6 weeks (16.9%). Recurrence of pericardial effusion after drainage without any sign of pericardial inflammation occurred in 68 out of 110 patients at a longer follow-up (61.8 %). At multivariate analysis only inflammatory cells in pericardial fluid was associated with PCIS and pericardiocentesis with pericardial effusion recurrency. CONCLUSION: Our data support the need of caution with the use of pericardiocentesis in asymptomatic patients with large pericardial effusion as it is often associated with pericardial effusion recurrence. Of interest the presence of inflammatory cells in the pericardial fluid is associated with PCIS after pericardial drainage procedures.
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Drenagem , Derrame Pericárdico , Pericardiocentese , Recidiva , Humanos , Derrame Pericárdico/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Pericardite/etiologia , Técnicas de Janela Pericárdica , Pericardiectomia , Traumatismos Cardíacos/complicaçõesRESUMO
People suffering from diabetes mellitus commonly have to face diabetic retinopathy (DR), an eye disease characterized by early retinal neurodegeneration and microvascular damage, progressively leading to sight loss. The Ins2Akita (Akita) diabetic mouse presents the characteristics of DR and experimental drugs can be tested on this model to check their efficacy before going to the clinic. Topical administration of Nerve Growth Factor (NGF) has been recently demonstrated to prevent DR in the Akita mouse, reverting the thinning of retinal layers and protecting the retinal ganglion cells (RGCs) from death. In this study, we characterize the effects of topical NGF on neuroretina function, quantified with the electroretinogram (ERG). In particular, we show that NGF can ameliorate RGC conduction in the retina of Akita mice, which correlates with a recovery of retinal nerve fiber plus ganglion cell layer (RNFL-GCL) structure. Overall, our preclinical results highlight that topical administration of NGF could be a promising therapeutic approach for DR, being capable of exerting a beneficial impact on retinal functionality.
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Diabetes Mellitus Experimental , Retinopatia Diabética , Animais , Camundongos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Modelos Animais de Doenças , Insulina/metabolismo , Fator de Crescimento Neural/farmacologia , Retina/metabolismoRESUMO
Diabetes-driven retinal neurodegeneration has recently been shown to be involved in the initial phases of diabetic retinopathy, raising the possibility of setting up a preventive strategy based on early retinal neuroprotection. To make this possible, it is crucial to identify a biomarker for early retinal neurodegeneration. To this end, in this study, we verified and confirmed that, in the Akita mouse model of diabetes, the thinning of the retinal nerve fiber layer/ganglion cell layer (the RNFL/GCL-the layer that contains the retinal ganglion cells) precedes the death of these same cells, suggesting that this dysfunction is a possible biomarker of retinal neurodegeneration. We then confirmed the validity of this assumption by starting a neuroprotective treatment (based on nerve growth factor eye drops) in concert with the first demonstration of RNFL/GCL thinning. In this way, it was possible not only to avoid the loss of retinal ganglion cells but also to prevent the subsequent development of the microvascular stage of diabetic retinopathy. In conclusion, in the case of diabetes, the thinning of the RNFL/GCL appears to be both a valid biomarker and a pharmacological target of diabetic retinopathy; it precedes the development of vascular dysfunctions and represents the ideal starting point for prevention.
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Diabetes Mellitus , Retinopatia Diabética , Animais , Camundongos , Retinopatia Diabética/tratamento farmacológico , Retina , Células Ganglionares da Retina , Biomarcadores , Fibras NervosasRESUMO
Pericardial effusion is the most common manifestation of pericardial diseases during pregnancy. This effusion is benign, mild, or moderate, well tolerated, with spontaneous resolution after delivery; no specific treatment is required. Acute pericarditis is the second most common condition, usually requiring medical therapy during pregnancy. Cardiac tamponade and constrictive pericarditis are rare in pregnancy. Pre-pregnancy counselling is essential in women of childbearing age with recurrent pericarditis to plan pregnancy in a phase of disease quiescence and to review therapy. High-dose aspirin or nonselective nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can be used up to the 20th week of gestation. Low-dose prednisone (2.5-10 mg/d) can be administered throughout pregnancy. All of these medications, apart from high-dose aspirin, may be used during lactation. Colchicine is compatible with pregnancy and breastfeeding, and it can be continued throughout pregnancy to prevent recurrences. Appropriate follow-up with a multidisciplinary team with experience in the field is recommended throughout pregnancy to ensure good maternal and fetal outcomes.
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Tamponamento Cardíaco , Derrame Pericárdico , Pericardite Constritiva , Pericardite , Gravidez , Humanos , Feminino , Pericardite/terapia , Pericardite/tratamento farmacológico , Aspirina/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêuticoRESUMO
PURPOSE: There is no valid medical treatment for diabetic retinopathy mostly because its pathogenesis remains largely unknown. Early stages of diabetic retinopathy, just like glaucoma, are characterized by the loss of retinal ganglion cells. Whether the two diseases may share a similar pathogenic background is unknown. METHODS: To clarify this issue the thickness of retinal nerve fiber layer was studied in vivo by optical coherence tomography in 10 Ins2Akita (diabetic) and 10 C57BL/6J (control) mice. The number of retinal ganglion cells and retina's surface covered by neurofilaments were quantified ex vivo in 12 normoglycemic DBA/2J (glaucoma) and 11 diabetic (alloxan-induced) DBA/2J mice (glaucoma + diabetes). RESULTS: At 16 weeks of age retinal nerve fiber layer was significantly thinner in Ins2Akita mice confirming the neurodegenerative impact of diabetes. Number of retinal ganglion cells and retina's surface covered by neurofilaments were similar in normoglycemic and diabetic DBA/2J mice with the exception of the superior quadrant where the number of retinal ganglion cells was increased in animals with glaucoma + diabetes. CONCLUSIONS: In presence of glaucoma, diabetes is unable to induce further retinal ganglion cells loss. The hypothesis that the mechanism leading to retinal ganglion cells loss may be shared by the two diseases cannot be ruled out. Whether early diabetes-driven retinal neurodegeneration could be prevented by neuroprotective treatment proven to be effective in case of glaucoma, remains to be clarified.
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Diabetes Mellitus , Retinopatia Diabética , Glaucoma , Camundongos , Animais , Células Ganglionares da Retina/patologia , Retinopatia Diabética/metabolismo , Camundongos Endogâmicos DBA , Camundongos Endogâmicos C57BL , Glaucoma/diagnóstico , Glaucoma/metabolismo , Modelos Animais de Doenças , Diabetes Mellitus/metabolismoRESUMO
AIMS: To identify peripheral blood cellular correlates of active pericarditis and to verify whether peripheral blood neutrophils, lymphocytes and the neutrophil to-lymphocyte ratio (NLR) are associated with disease phenotype or prognosis. METHODS: Observational prospective study on a cohort of 63 patients with idiopathic pericarditis followed for 12 months after each pericarditis recurrence. Two distinct analyses were performed: the "index attack" analysis focused on the first pericarditis episode in each patient, while the "all attacks" analysis included all episodes occurring during the study. RESULTS: Absolute and relative neutrophilia and lymphopenia, together with high NLR, were observed during active pericarditis, as compared with disease remission, at both analyses. Neutrophils showed a positive correlation with plasma C-reactive protein levels, while lymphocyte count showed a negative correlation. Relative neutrophil count was higher, and lymphocyte count lower in patients with pleural effusion; a higher NLR and lower absolute lymphocyte count were observed in those with peritoneal involvement. No correlations were found between peripheral blood neutrophil or lymphocyte counts and size of pericardial effusion, or with the presence of myocardial involvement. Peripheral neutrophilia, lymphopenia and NLR during acute attacks predicted the number of recurrences in the following 12 months. CONCLUSIONS: Peripheral blood neutrophilia and lymphopenia are typical of acute idiopathic pericarditis. Acute attacks of pericarditis are associated with neutrophilia and lymphopenia, as compared with disease remission. During acute attacks, neutrophilia and lymphopenia reflect the extent of serosal inflammation and could help to customize therapeutic management after remission has been achieved.
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Doenças da Medula Óssea , Linfopenia , Pericardite , Humanos , Neutrófilos , Estudos Prospectivos , Linfopenia/diagnóstico , Linfócitos , Contagem de Linfócitos , Prognóstico , Inflamação , Pericardite/diagnóstico , Pericardite/terapia , Estudos RetrospectivosRESUMO
Specific and effective preventive treatment for diabetic retinopathy (DR) is presently unavailable, mostly because the early stages of the complication have been, until recently, poorly understood. The recent demonstration that the vascular phase of DR is preceded and possibly caused by the neurodegeneration of retinal ganglion cells suggests that DR could, at least theoretically, be prevented through an early neuroprotective approach. The aims of our study were to clarify the natural history of diabetes-driven retinal neurodegeneration and to verify the possibility to prevent DR using topical nerve growth factor (NGF). The results of the study show that retinal neurodegeneration, characterized by the loss of retinal ganglion cells represents a relatively early phenomenon of diabetes (between 5 and 16 weeks of age), which tends to be self-limiting in the long run. Neurodegeneration is followed by the development of DR-related vascular dysfunctions, as confirmed by the development of acellular capillaries and the loss of retinal pericytes. Both retinal neurodegeneration and subsequent vascular dysfunction can be successfully prevented by topical NGF administration. These findings suggest that: 1) The first stage of DR consists in a self-limiting retinal neurodegeneration 2) The demonstrated effectiveness of topical NGF in the prevention of DR could be rapidly translated into clinical practice.
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BACKGROUND: Pre-eclampsia has a major impact on renal function as shown by the development of proteinuria and podocyturia. How the systemic, soluble Fms-like tyrosine kinase-1 (sFlt-1)-driven inhibition of vascular endothelial growth factor (VEGF) activity detected in pre-eclampsia directly affects renal function remains unknown. The aim of the study was to clarify whether a non-canonical, renal-centred escape from VEGF inhibition in the case of pre-eclamptic pregnancy might have a direct impact on renal function. METHODS: We evaluated plasma and urinary VEGF and placental growth factor (PlGF), plasma sFlt-1 and carbonic anhydrase IX (CAIX), albuminuria and podocyturia in 18 women with uncomplicated pregnancy, 21 with pre-eclampsia and 18 non-pregnant. The three groups were matched for age and the pregnant groups also for gestational age at enrolment. RESULTS: Plasma VEGF was reduced in uncomplicated (P = 0.001) and pre-eclamptic (P = 0.0003) pregnancies when compared with controls. In uncomplicated pregnancy, the dysfunction was balanced by an increase (P = 0.009) of plasma PlGF. Increased (P = 0.0001) plasma CAIX in pre-eclampsia was in line with hypoxia. Pre-eclampsia resulted in a paradoxical increase (P = 0.0004) of urinary excretion of VEGF. Urinary concentrations of VEGF and podocytes were correlated to each other (r2 = 0.48, P < 0.0005) but also to plasma sFlt-1 (r2 = 0.56, P < 0.0001 and r2 = 0.23, P = 0.03, respectively). CONCLUSIONS: In the case of pre-eclampsia, the systemic VEGF inhibition leads the kidney, possibly the podocyte, to increase the VEGF synthesis. The mechanisms leading to local VEGF overproduction or the overproduced VEGF itself are reasonably involved in the pathogenesis of podocyturia and, as a consequence, renal dysfunction in pre-eclampsia.
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Nefropatias , Pré-Eclâmpsia , Biomarcadores , Feminino , Humanos , Fator de Crescimento Placentário , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/patologia , Gravidez , Fator A de Crescimento do Endotélio Vascular , Receptor 1 de Fatores de Crescimento do Endotélio VascularRESUMO
This review summarizes the currently available evidence on the management of acute and recurrent pericarditis during pregnancy, focusing on the safety of diagnostic procedures and treatment options for the mother and fetus. Family planning should be addressed in women with recurrent pericarditis of reproductive age and adjustment of therapy should be considered before a planned pregnancy. The treatment of pericarditis in pregnancy is similar to that for non-pregnant women but considers current knowledge on drug safety during pregnancy and lactation. The largest case series on this topic described 21 pregnancies with idiopathic recurrent pericarditis. Pregnancy should be planned in a phase of disease quiescence. Non-steroidal anti-inflammatory drugs can be used at high dosages until the 20th week of gestation (except low-dose aspirin 100 mg/die). Colchicine is allowed until gravindex positivity; after this period, administration of this drug during pregnancy and lactation should be discussed with the mother if its use is important to control recurrent pericarditis. Prednisone is safe if used at low-medium doses (2.5-10 mg/die). General outcomes of pregnancy in patients with pericarditis are good when the mothers are followed by a multidisciplinary team with experience in the field.
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Pericardite , Feminino , Humanos , Pericardite/diagnóstico , Pericardite/tratamento farmacológico , GravidezRESUMO
OBJECTIVE: Biochemical and cytological pericardial fluid (PF) analysis is essentially based on the knowledge of pleural fluid composition. The aim of the present study is to identify reference intervals (RIs) for PF according to state-of-art methodological standards. METHODS: We prospectively collected and analysed the PF and venous blood of consecutive subjects undergoing elective open-heart surgery from July 2017 to October 2018. Exclusion criteria for study enrolment were evidence of pericardial diseases at preoperatory workup or at intraoperatory assessment, or any other condition that could affect PF analysis. RESULTS: The final study sample included 120 patients (median age 69 years, 83 men, 69.1%). The main findings were (1) High levels of proteins, albumin and lactate dehydrogenase (LDH), but not of glucose and cholesterol (2) High cellularity, mainly represented by mesothelial cells. RIs for pericardial biochemistry were: protein content 1.7-4.6 g/dL PF/serum protein ratio 0.29-0.83, albumin 1.19-3.06 g/dL, pericardium-to-serum albumin gradient 0.18-2.37 g/dL, LDH 141-2613 U/L, PF/serum LDH ratio 0.40-2.99, glucose 80-134 mg/dL, total cholesterol 12-69 mg/dL, PF/serum cholesterol ratio 0.07-0.51. RIs for pericardial cells by optic microscopy were: 278-5608 × 106 nucleated cells/L, 40-3790 × 106 mesothelial cells/L, 35-2210 × 106 leucocytes/L, 19-1634 × 106 lymphocytes/L. CONCLUSIONS: PF is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Physicians should stop to interpret PF as exudate or transudate according to tools not validated for this setting.
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Albuminas/análise , Colesterol/análise , L-Lactato Desidrogenase/análise , Líquido Pericárdico/química , Idoso , Contagem de Células , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Líquido Pericárdico/citologia , Valores de Referência , Estudos RetrospectivosRESUMO
PURPOSE: The aim of this study was to characterize the response to aflibercept in a mouse model of type 3 neovascularization, the neoretinal vascularization (NRV) 2 mouse line. METHODS: Twelve NRV2 mice were assigned to one of the following groups: (1) 6 mice were injected with aflibercept 3 µg/g at postnatal day (P) 15 ("aflibercept" group), and (2) the remaining 6 mice did not receive any treatment ("placebo" group). The mice were examined at P30 and P44. RESULTS: The NRV mice's retinas were characterized by regions of depigmentation that were topographically associated with hyperfluorescent lesions seen on fluorescein angiography (FA) images. On optical coherence tomography images, intraretinal neovascularizations were visualized as hyperreflective lesions mainly localized within the outer plexiform and outer nuclear layers. The average number of intraretinal neovascular lesions visualized on FA at P30 was 5.0 ± 2.2 in the aflibercept group and 20.7 ± 2.4 in the placebo group (p < 0.0001). At P44, the average number of intraretinal lesions was still lower in the aflibercept group, although this difference was not statistically significant (p = 0.088). CONCLUSION: Aflibercept therapy was effective in inhibiting pathologic angiogenesis in the NRV2 mouse model. However, the successive treatment washout resulted in an increase in the number of lesions.
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Receptores de Fatores de Crescimento do Endotélio Vascular , Tomografia de Coerência Óptica , Inibidores da Angiogênese/uso terapêutico , Animais , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Camundongos , Imagem Multimodal , Neovascularização Patológica/tratamento farmacológico , Proteínas Recombinantes de FusãoRESUMO
AIMS: Novel therapies are needed for recurrent pericarditis, particularly when corticosteroid dependent and colchicine resistant. Based on limited data, interleukin-1 blockade with anakinra may be beneficial. The aim of this multicentre registry was to evaluate the broader effectiveness and safety of anakinra in a 'real world' population. METHODS AND RESULTS: This registry enrolled consecutive patients with recurrent pericarditis who were corticosteroid dependent and colchicine resistant and treated with anakinra. The primary outcome was the pericarditis recurrence rate after treatment. Secondary outcomes included emergency department visits, hospitalisations, corticosteroid use and adverse events. Among 224 patients (46 ± 14 years old, 63% women, 75% idiopathic), the median duration of disease was 17 months (interquartile range 9-33). Most patients had elevated C-reactive protein (91%) and pericardial effusion (88%). After a median treatment of 6 months (3-12), pericarditis recurrences were reduced six-fold (2.33-0.39 per patient per year), emergency department admissions were reduced 11-fold (1.08-0.10 per patient per year), hospitalisations were reduced seven-fold (0.99-0.13 per patient per year). Corticosteroid use was decreased by anakinra (respectively from 80% to 27%; P < 0.001). No serious adverse events occurred; adverse events consisted mostly of transient skin reactions (38%) at the injection site. Adverse events led to discontinuation in 3%. A full-dose treatment duration of over 3 months followed by a tapering period of over 3 months were the therapeutic schemes associated with a lower risk of recurrence. CONCLUSION: In patients with recurrent pericarditis, anakinra appears efficacious and safe in reducing recurrences, emergency department admissions and hospitalisations.
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Corticosteroides/administração & dosagem , Colchicina/uso terapêutico , Resistência a Medicamentos , Fatores Imunológicos/administração & dosagem , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Pericardite/tratamento farmacológico , Adolescente , Corticosteroides/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Redução da Medicação , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pericardite/diagnóstico por imagem , Recidiva , Sistema de Registros , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown. METHODS: To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function. RESULTS: Our GWAS meta-analysis included association results for up to 19,406 individuals of European descent with type 1 diabetes. We identified 16 genome-wide significant risk loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM). Mutations in COL4A3 are implicated in heritable nephropathies, including the progressive inherited nephropathy Alport syndrome. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of diabetic kidney disease, including albuminuria and ESKD, and demonstrated a significant association with GBM width; protective allele carriers had thinner GBM before any signs of kidney disease, and its effect was dependent on glycemia. Three other loci are in or near genes with known or suggestive involvement in this condition (BMP7) or renal biology (COLEC11 and DDR1). CONCLUSIONS: The 16 diabetic kidney disease-associated loci may provide novel insights into the pathogenesis of this condition and help identify potential biologic targets for prevention and treatment.
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Autoantígenos/genética , Colágeno Tipo IV/genética , Diabetes Mellitus Tipo 1/genética , Nefropatias Diabéticas/genética , Estudo de Associação Genômica Ampla , Membrana Basal Glomerular , Mutação , Estudos de Coortes , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Data concerning idiopathic recurrent pericarditis in pregnancy are scarce. OBJECTIVES: To evaluate the management and outcome of idiopathic recurrent pericarditis during pregnancy. METHODS AND RESULTS: Twenty-one pregnancies were evaluated in fourteen women with a history of recurrent idiopathic pericarditis (mean maternal age 31.5â¯years, mean gestational age 39.0â¯weeks), and subdivided in 2 cohorts: eight pregnancies were analyzed retrospectively (2002-2010), thirteen (2011-2017) prospectively and followed according a predefined management protocol. Ten pregnancies were uneventful, three ended in spontaneous early abortion, one fetal death occurred at 19â¯weeks. Recurrences of pericarditis occurred in eight and were treated by adding NSAIDs in two cases; in five cases the dose of corticosteroids was increased and in two cases aspirin was started/increased; paracetamol was always allowed. Colchicine was used in two cases in the prospective cohort. HELLP syndrome occurred in one patient, which resolved after delivery, and one patient experienced arterial hypertension and elevated transaminase. All infants had a good outcome (mean birth weight 3114â¯g, 10 males). Birth weight was significantly lower in the retrospective cohort (respectively 2806â¯g vs. 3320â¯g, p-value 0.017) in which higher doses of corticosteroids were used (median dose respectively 10.0â¯mg vs. 2.5â¯mg, p-value 0.048). Five recurrences of pericarditis occurred after delivery, easily treated with standard therapy. CONCLUSION: General outcomes of pregnancy in patients with idiopathic recurrent pericarditis is good, especially when patients are carefully followed by multidisciplinary teams according to standardized protocols.
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Gerenciamento Clínico , Pericardite/diagnóstico , Pericardite/terapia , Complicações Cardiovasculares na Gravidez/diagnóstico , Complicações Cardiovasculares na Gravidez/terapia , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Estudos de Coortes , Feminino , Seguimentos , Humanos , Gravidez , Recidiva , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the plasma concentration of the soluble form of the urokinase-type plasminogen activator receptor ((s)uPAR), an established biomarker of chronic inflammation, in patients affected by neovascular age-related macular degeneration. METHODS: Forty consecutive patients affected by age-related macular degeneration and 52 subjects with no history of the disease were included in this case-control study. The two groups of individuals considered for the study were matched for age, sex, and class of medications taken. Plasma concentration of suPAR was measured using a specific ELISA assay (suPARnostic, Birkeroed, Denmark). RESULTS: The case and control groups were similar for age, gender distribution, weight, height, and systolic and diastolic blood pressure, as well as for dyslipidemia and high blood pressure medication (P > 0.28). The plasma concentrations of suPAR were significantly increased in patients with neovascular age-related macular degeneration when compared to controls (6.19 ± 2.2 ng/ml, vs 5.21 ± 1.5, respectively, mean ± SD P = 0.01). CONCLUSIONS: Patients with neovascular age-related macular degeneration display increased plasma levels of suPAR, suggesting that chronic inflammation may be involved in the pathogenesis of the disease.
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Inflamação/sangue , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Degeneração Macular Exsudativa/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Inflamação/diagnóstico , Macula Lutea/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Tomografia de Coerência Óptica , Degeneração Macular Exsudativa/diagnósticoRESUMO
It usually takes several years (in some cases, decades) for predisposed individuals to move from the onset of type 1 or type 2 diabetes to the development of microalbuminuria, the first sign of diabetic nephropathy. This long, complication-free, period represents the best possible moment to start a successful preventive strategy (primary prevention) aimed to avoid or at least to postpone the increase of albumin excretion rate. Prevention is based on understanding and counteracting the initial mechanisms leading to the development of the disease and unfortunately, in case of diabetic nephropathy, most of them remain unclear. Little is also known about which, among endothelial cells and podocytes, represent the first glomerular target of the complication. Selective damage of the endothelium or of the podocyte results, as a common consequence, in an increase of albumin excretion rate. Albuminuria by itself cannot therefore be of help to solve the case. Endothelium and podocytes are involved in a continuous cross-talk and by studying the impact of diabetes on this "communication" process it should be possible to obtain some information regarding the weak component of the glomerular filter. Finally, the careful investigation of the mechanisms leading to the development podocyturia, a recently identified glomerular dysfunction associated to the pathogenesis of diabetic nephropathy, could contribute to shed some more light on the very early stages of this complication.
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Nefropatias Diabéticas/patologia , Podócitos/patologia , Animais , HumanosRESUMO
PURPOSE OF REVIEW: This review aims to summarize the role of the interleukin-1 (IL-1) blocking agents in cardiovascular diseases, briefly describing the pathogenetic rationale and the most relevant clinical studies. RECENT FINDINGS: IL-1 is a pivotal cytokine of the innate immune system. Anti-IL-1 agents are currently used for the treatment of several autoimmune and autoinflammatory conditions. Recently, the role of IL-1 has also emerged in cardiovascular diseases. Indeed, two recent randomized controlled trials have shown that the IL-1 receptor antagonist anakinra is effective for the treatment of idiopathic recurrent pericarditis and the IL-1ß blocking agent canakinumab is effective in reducing myocardial infarction in people at risk. Interestingly, interfering with IL-1 has proved to be also effective in other cardiovascular manifestations, such as myocarditis, arrhythmias, and heart failure. Blocking the IL-1 pathway is a possible new therapeutic strategy, potentially leading to innovative therapies in many acute and chronic cardiovascular diseases.
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Anticorpos Monoclonais/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Interleucina-1/antagonistas & inibidores , Infarto do Miocárdio/prevenção & controle , Pericardite/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Recently a range of ocular manifestations such as retinal and lens amyloid-beta accumulation and retinal nerve fiber layer loss have been proposed as potential biomarkers in Alzheimer disease (AD). The TgCRND8 mouse model of AD exhibits age-dependent amyloid ß (Aß) oligomers accumulation and cognitive defects, amyloid plaques and hyperphosphorylated Tau deposition and inflammation. We proved the correlation between ocular pathologies and AD, observing increased levels of p-APP and p-Tau, accumulation of Aß oligomers in the retina, eye, and optic nerve. The accumulation of amyloid markers was significantly stronger in the retinal ganglion cell (RGC) layer, suggesting that RGC might be more susceptible to degeneration. We detected a thinning of the RGC layer as well as RGC death in the retina of TgCRND8 mice, by using a combination of Optical Coherence Tomography (OCT), immunofluorescence, immunohistochemistry and Western blotting techniques. We proved for the first time the key role of C-Jun N-terminal Kinase (JNK) in the ocular degeneration. In support of this, the administration of the JNK inhibitor, D-JNKI1, was able to counteract the Aß and p-Tau accumulation in the retina of TgCRND8 mice, and consequently reduce RGCs loss. These results confirm that degenerative changes in the retina/eye of AD mouse model mirrors the events observed in the brain parenchyma. Ocular changes can be detected by non-invasive imaging techniques, such as OCT, to study and test different therapeutic strategies against degenerative events associated to AD.