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1.
BMC Nephrol ; 21(1): 430, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046028

RESUMO

BACKGROUND: Medullary sponge kidney (MSK) is a rare disease characterized by cystic dilatation of papillary collecting ducts. Intravenous urography is still considered the gold standard for diagnosis. We identified a cohort of patients from our outpatient clinic with established diagnosis of MSK to outline some ultrasonographic characteristics that may help establish a diagnosis. METHODS: We conducted a retrospective study of patients seen between January 1st 2009 and January 1st 2019 in our clinic. Out of 4321 patients, 18 had a diagnosis of MSK. We reviewed their clinical and family history, laboratory data and imaging studies. Specifically, we focused on ultrasound imaging. RESULTS: Patients were referred to our outpatient clinic because of renal impairment (44%), family history of nephropathy (17%), nephrolithiasis or an established diagnosis of MSK (39%). Seventy-two percent of patients presented with chronic kidney disease, 22% required hemodialysis. Urinary tract infections (44%), nephrolithiasis (33%), microscopic hematuria (50%) and proteinuria (44%) were reported. Seven patients underwent computed tomography; all of them received ultrasound. Ultrasound examination showed bilateral renal cysts, usually small and located in the renal medulla, and microcalcifications located in the medulla or within the cysts. CONCLUSION: We identified a peculiar tetrad associated with MSK: 1) hypoechoic medullary areas, 2) hyperechoic spots, 3) microcystic dilatation of papillary zone, 4) multiple calcifications (linear, small stones or calcified intracystic sediment) in each papilla. The presence of this diagnostic tetrad, added to laboratory data and clinical history, could be helpful in the differential diagnosis to identify patients with MSK.


Assuntos
Rim/diagnóstico por imagem , Rim em Esponja Medular/diagnóstico por imagem , Ultrassonografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcinose/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Rim/patologia , Cálculos Renais/diagnóstico por imagem , Medula Renal/diagnóstico por imagem , Medula Renal/patologia , Masculino , Rim em Esponja Medular/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
2.
Obes Surg ; 27(2): 357-363, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27389676

RESUMO

BACKGROUND: Carotid intima-media thickness (C-IMT) can be considered as an early marker of atherosclerosis, thus representing a reliable cardiovascular risk predictor. Bariatric surgery decreases the burden of cardiovascular disease in obese patients through complex mechanisms, of which weight loss is merely the most evident epiphenomenon. The aim of this study is to evaluate C-IMT variations in patients undergoing Roux-en-Y gastric bypass (RYGB) and possible correlations with biometric parameters and cardiovascular risk factors. METHODS: Thirty patients undergoing RYGB for morbid obesity were enrolled for carotid artery B-mode ultrasound evaluation before surgery and at 1-, 3-, 6-, and 12-month follow-up; C-IMT was recorded at three levels (bulb, common, and internal carotid). At each one of the follow-ups, biometric and serohematic parameters were also collected. RESULTS: The 22 patients who completed the follow-up and were included in the study showed significant C-IMT reduction at all three levels at 12-month follow-up (p < 0.001). Along with a significant BMI reduction and diabetes/hypertension remission, we found a considerable decrease in total cholesterol (219 vs 164 mg/dl; p < 0.001) and uric acid (5.6 vs 4.5 mg/dl; p < 0.01) and a significant increase in HDL cholesterol (43.9vs59.2 mg/dl; p < 0.001). The data imply that the mean 10-year cardiovascular risk score drops by nearly 50 % (5.7 ± 5.6 vs. 2.9 ± 2.7 %, p < 0.001) according to Framingham cardiovascular risk stratification. CONCLUSIONS: RYGB is associated with significant decrease in C-IMT at 1 year. Pathophysiologic processes underlying such a variation, probably involving lipid and urate metabolism and their correlation with cardiovascular risk reduction should be confirmed by long-term prospective trials.


Assuntos
Artéria Carótida Primitiva/patologia , Espessura Intima-Media Carotídea , Derivação Gástrica , Obesidade Mórbida/cirurgia , Adulto , Idoso , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Seguimentos , Derivação Gástrica/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/patologia , Fatores de Risco , Redução de Peso/fisiologia , Adulto Jovem
3.
Nephrol Dial Transplant ; 22(2): 529-37, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17071958

RESUMO

BACKGROUND: Prostacyclin is an easy-to-use and safe antihaemostatic drug for continuous renal replacement therapies (RRTs). No study has been performed so far about its use in critically ill patients with acute renal failure (ARF) treated with sustained low-efficiency dialysis (SLED), a hybrid modality between conventional intermittent and continuous RRTs. METHODS: We studied 35 consecutive ICU patients with ARF, in whom data on safety and efficacy were prospectively collected in a single-centre experience over 15 months since August 2001. There were 25 males and 10 females; mean age, 72.1 (SD 11.4); mean APACHE II score at ICU admission, 24 (range 14-43); at RRT start, 27.4 (20-43); 28 patients (80%) were on mechanical ventilation and 17 (48.6%) had sepsis. SLED was performed using a conventional dialysis machine, with blood flow at 200 ml/min, bicarbonate-based ultrapure dialysate running at 100 ml/min, dialysate temperature 35 degrees C and low-flux polysulfone filters. Prostacyclin, under the form of its synthetic analogue epoprostenol, was infused at 6 ng/kg/min before the filter. RESULTS: Out of 185 daily sessions performed (8-10 h, median 4 per patient, range 1-19), 19 (in 11 patients) were prematurely interrupted (10.3%; 95% CI: 5.4-18.6), after an average 58.5% of the prescribed treatment time (nine sessions in six patients for circuit clotting). This finding compared favourably with the experience we had at our unit using SLED with saline flushes. With the use of prostacyclin, two episodes of upper gastrointestinal bleeding were observed in 2/35 patients during SLED (5.7%; 95% CI: 0.7-19.2), corresponding to 1.1 episodes per 100 person-day on SLED. Therapeutic intervention for hypotension (fluids and/or vasopressor increase) was required in 45/185 (in 20 patients) of the sessions monitored (24.3%; 95% CI: 17.4-32.9); two sessions had to be interrupted because of refractory hypotension. Urea reduction ratio was 0.50 (SD 0.12); mean prescribed and obtained net ultrafiltration were 1.96 l (range 0.5-5.0) and 1.99 l (0.5-5.0), respectively. In-hospital mortality was 46%; mortality predicted by the APACHE II model at ICU admission was 42%; at SLED start, 51%. CONCLUSIONS: Prostacyclin is a safe and effective antihaemostatic agent for SLED.


Assuntos
Injúria Renal Aguda/terapia , Epoprostenol/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Diálise Renal/métodos , Idoso , Estado Terminal/terapia , Soluções para Diálise , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Masculino , Estudos Retrospectivos , Resultado do Tratamento
4.
Nephrol Dial Transplant ; 21(5): 1402-6, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16504979

RESUMO

BACKGROUND: Previous studies have shown that a single haemodialysis (HD) session removes about one-third of the linezolid dose administered, but it is unknown whether in critically ill patients with renal failure on intermittent HD, this removal adversely affects serum antibiotic concentrations. METHODS: Five male critically ill patients (mean age 75 years, range 68-82; APACHE II score 26.4, range 23-29; survival 2/5) with sepsis and renal failure on haemodialysis, were administered i.v. linezolid, 600 mg every 12 h. Serum antibiotic levels were measured by high-performance liquid chromatography/mass spectrometry. We classified trough concentrations as 'with HD' when a HD session was performed after linezolid infusion, and 'without HD' otherwise. We also computed population pharmacokinetics while patients were on-dialysis and off-dialysis. RESULTS: A total of 222 serum linezolid concentrations were available over 36 days of antibiotic therapy, during which patients underwent 31 HD sessions. Trough serum linezolid levels averaged 5.83 mg/l (range 1.48-15.84), exceeding 4.0 mg/l in 68.9% of the samples; however, the trough levels 'with HD' were lower than those 'without HD' (4.68 mg/l [range 1.48-9.07] vs 6.74 mg/l [range 2.04-15.84], P<0.001). Clearance and half-life were 6.0 l/h and 4.0 h, respectively, while patients were on-dialysis, and 4.4 l/h and 7.3 h, respectively, when they were off-dialysis. CONCLUSIONS: HD can significantly reduce serum linezolid levels in critically ill patients with renal failure.


Assuntos
Acetamidas/administração & dosagem , Acetamidas/sangue , Falência Renal Crônica/terapia , Oxazolidinonas/administração & dosagem , Oxazolidinonas/sangue , Diálise Renal/métodos , APACHE , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/sangue , Cuidados Críticos , Estado Terminal , Relação Dose-Resposta a Droga , Esquema de Medicação , Seguimentos , Humanos , Infusões Intravenosas , Falência Renal Crônica/diagnóstico , Testes de Função Renal , Linezolida , Masculino , Projetos Piloto , Medição de Risco , Estudos de Amostragem , Sensibilidade e Especificidade , Taxa de Sobrevida , Resultado do Tratamento
6.
Nephrol Dial Transplant ; 20(9): 1976-80, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15998652

RESUMO

BACKGROUND: Thus far, there have been no controlled studies to examine optimal levels of energy provision in critically ill patients with acute renal failure (ARF) receiving artificial nutrition. METHODS: After a 24 h nitrogen-free regimen (20% dextrose), we assigned during an open-label, AB/BA-crossover-trial, 10 ARF patients receiving both total parenteral nutrition (TPN) and renal replacement therapy (seven males; mean age 72 years, range 60-83; mean APACHE II score 27.1, range 23-34, mechanical ventilation 8/10) to a lower calorie-TPN regimen (30 kcal/kg/day) and to a higher calorie-TPN regimen (40 kcal/kg/day), each for 3 days. Nitrogen intake was 0.25 g/kg/day for both regimens. We estimated nitrogen balance, protein catabolic rate and urea generation rate by urea kinetic methods based on both timed blood samples of serum urea and direct urea quantification from dialysis fluid. RESULTS: Two patients were excluded from the analysis (due to death and serum triglycerides above 5.1 mmol/l, respectively). Compared with the lower calorie-TPN, the higher calorie-TPN regimen did not improve estimated nitrogen balance [+1.55 g/day (95% confidence interval: -0.95 to +4.05, P = 0.18)], protein catabolic rate [-0.10 g/kg/day (-0.33 to +0.14, P = 0.35)], or urea generation rate [-1.3 mg/min (-5.2 to +2.7, P = 0.46)], whereas it increased serum triglycerides [+1.36 mmol/l (+0.53 to +2.19, P = 0.007)], glucose [+1.15 mmol/l (+0.07 to +2.24, P = 0.041)], insulin need [+20.4 U/day (+8.3 to +32.6, P = 0.006)] and nutritional fluid administration [+468 ml/day (+370 to +566, P<0.001)]. CONCLUSIONS: The present study, conducted in a small group of subjects, shows that in critically ill patients with ARF on a nitrogen intake of 0.25 g/kg/day, an energy provision of 40 kcal/kg/day does not improve nitrogen balance estimates compared with a 30 kcal/kg/day intake; instead, it may increase the risk of artificial nutrition-related side-effects.


Assuntos
Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/terapia , Nitrogênio/metabolismo , Nutrição Parenteral Total , Estudos Cross-Over , Proteínas Alimentares/metabolismo , Ingestão de Energia , Metabolismo Energético , Humanos , Projetos Piloto , Ureia/metabolismo
7.
Crit Care Med ; 32(12): 2437-42, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15599148

RESUMO

OBJECTIVE: To study the removal of linezolid, a new oxazolidinone antibiotic, by renal replacement therapy in patients with acute renal failure. DESIGN: Prospective, single-dose pharmacokinetic study. SETTING: Renal intensive care unit of a tertiary university hospital. PATIENTS: Fifteen critically ill patients with oliguric acute renal failure on renal replacement therapy (seven males, mean age 72.3 yrs, range 60-94; Acute Physiology and Chronic Health Evaluation II score 24.9, range 18-36; mechanical ventilation ten of 15). INTERVENTIONS: All patients received 600 mg of intravenous linezolid before starting renal replacement therapy, which consisted of intermittent hemodialysis lasting 3-4 hrs in eight patients, sustained low-efficiency dialysis lasting 8 hrs in five patients, and continuous venovenous hemofiltration lasting 10.5-12 hrs in two patients. MEASUREMENTS AND MAIN RESULTS: Linezolid concentrations were measured by liquid chromatography/mass spectrometry methods on serum and dialysate/ultrafiltrate samples. At the start of renal replacement therapy, serum levels averaged 11.91 mg/L (range 5.49-21.52) and dropped at the end to levels <4 mg/dL (90% minimum inhibitory concentration values for Staphylococcus aureus) in three of eight patients on hemodialysis, three of five patients on sustained low-efficiency dialysis, and two of two patients on continuous venovenous hemofiltration. Mean removal of the drug was 193.7 mg with hemodialysis (32.3% of the dose administered), 205 mg with sustained low-efficiency dialysis (33.9%), and 74.8 mg (12.4%) and 105 (17.5%) mg following a continuous venovenous hemofiltration session lasting 10.5 and 12 hrs, respectively. CONCLUSIONS: In patients with acute renal failure, serum levels of linezolid can be reduced to the subtherapeutic range following renal replacement therapy.


Assuntos
Acetamidas/farmacocinética , Injúria Renal Aguda/terapia , Diálise/métodos , Hemofiltração/métodos , Oxazolidinonas/farmacocinética , Diálise Renal/métodos , APACHE , Acetamidas/administração & dosagem , Acetamidas/sangue , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida de Alta Pressão , Cuidados Críticos/métodos , Feminino , Seguimentos , Humanos , Injeções Intravenosas , Unidades de Terapia Intensiva , Linezolida , Masculino , Pessoa de Meia-Idade , Oxazolidinonas/administração & dosagem , Oxazolidinonas/sangue , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença
8.
Acta Biomed ; 75(2): 126-30, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15481703

RESUMO

We here describe two patients with metastatic renal cell cancer (mRCC) treated with immunotherapy in whom the metastases completely regressed after a period of progressive disease. The treatment schedule was based on repeated cycles of low-dose recombinant interleukin-2 and recombinant interferon-alpha, and was never changed during the course of the disease. The first patient received immunotherapy because of multiple bilateral lung metastases. Progressive disease, with mediastinal lymph node involvement and an increased number of lung metastases, was observed after 30 months of regularly repeated therapy; complete regression was achieved after 60 months of immunotherapy (after 16 immunotherapy cycles). The second patient began immunotherapy because of three small lung metastases. Disease progression was observed after three cycles, but complete regression was obtained about 16 months after the start of immunotherapy (after 5 immunotherapy cycles). Long-term low-dose immunotherapy may bring about an effective anti-tumour response even late in the course of the disease and after an initial disease progression.


Assuntos
Adenocarcinoma de Células Claras/secundário , Carcinoma de Células Renais/secundário , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Interleucina-2/uso terapêutico , Neoplasias Renais/patologia , Neoplasias Pulmonares/secundário , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/cirurgia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Terapia Combinada , Progressão da Doença , Esquema de Medicação , Quimioterapia Combinada , Evolução Fatal , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/secundário , Humanos , Imunoterapia , Interferon-alfa/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Nefrectomia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Indução de Remissão , Choque Cardiogênico/etiologia , Fatores de Tempo
9.
Ann Ital Med Int ; 19(1): 54-7, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15176709

RESUMO

A 22-year-old woman presented with effort dyspnea unresponsive to bronchodilators. Harsh respiratory sounds were audible at the neck. Thoracic and cardiac evaluation was normal. Spirometry revealed an obstructive ventilatory defect, and the flow-volume loop indicated upper airway obstruction. Bronchoscopy and tracheal computed tomography revealed a stenosis of the subglottic larynx. A biopsy specimen of the stenotic area of the trachea showed a normal mucosa and non-specific chronic inflammation. The tracheal stenosis was managed by means of endobronchial laser therapy, which led to the resolution of the patient's symptoms. As we could not identify any specific pathogenetic process, our final diagnosis was idiopathic subglottic tracheal stenosis.


Assuntos
Laringoestenose/diagnóstico , Terapia a Laser , Estenose Traqueal/diagnóstico , Adulto , Broncoscopia , Diagnóstico Diferencial , Dispneia/etiologia , Feminino , Cardiopatias/diagnóstico , Humanos , Laringoestenose/complicações , Laringoestenose/cirurgia , Pneumopatias/diagnóstico , Esforço Físico , Sons Respiratórios/etiologia , Espirometria , Tomografia Computadorizada por Raios X , Estenose Traqueal/complicações , Estenose Traqueal/cirurgia
10.
Nephrol Dial Transplant ; 19(4): 865-9, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15031342

RESUMO

BACKGROUND: Radiocontrast media (RCM) administration is a common cause of hospital-acquired acute renal failure, especially in high-risk patients, but mechanisms of nephrotoxicity have not been fully elucidated. Reactive oxidant species recently have been shown to play a role in experimental RCM nephropathy, while there is clinical evidence that acetylcysteine, an antioxidant drug, has a protective effect against RCM nephropathy in humans. However, no study has been published showing that RCM administration elicits oxidative stress in humans. METHODS: In an unselected series of patients undergoing elective cardiac catheterization for coronary artery angiography and/or angioplasty, we monitored the time course of plasma and urinary levels of free 3-nitrotyrosine (3-NT), a stable marker of peroxynitrite generation resulting from the in vivo reaction of superoxide and nitric oxide. Urinary 3-NT levels were measured as the ratio of urinary 3-NT to urinary creatinine. Measurements were taken at baseline, immediately after the procedure and at 24, 48 and 72 h. RESULTS: Twenty-six patients were studied (median age 67.5 years, range 42-86; baseline serum creatinine 1.0 mg/dl, 0.6-1.5; RCM dose 215 ml, 100-580). Plasma 3-NT levels slightly increased over the 72 h following the procedure (P<0.001), while urinary 3-NT levels peaked at the end of the procedure (P<0.001). Urinary 3-NT levels reached at the end of the procedure were proportional to the RCM dose administered (P = 0.017). CONCLUSIONS: The present study provides indirect evidence that RCM administration in humans is associated with an increased production of 3-NT. Further studies are needed to ascertain whether oxygen- and nitrogen-derived radical species play a major role in the pathogenesis of RCM-associated nephrotoxicity in the clinical setting.


Assuntos
Angiografia Coronária , Compostos Radiofarmacêuticos , Tirosina/análogos & derivados , Tirosina/sangue , Tirosina/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Kidney Int ; 65(3): 999-1008, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14871420

RESUMO

BACKGROUND: Systematic studies on safety and efficacy of enteral nutrition in patients with acute renal failure (ARF) are lacking. METHODS: We studied enteral nutrition-related complications and adequacy of nutrient administration during 2525 days of artificial nutrition in 247 consecutive patients fed exclusively by the enteral route: 65 had normal renal function, 68 had ARF not requiring renal replacement therapy, and 114 required renal replacement therapy. RESULTS: No difference was found in gastrointestinal or mechanical complications between ARF patients and patients with normal renal function, except for high gastric residual volumes, which occurred in 3.1% of patients with normal renal function, 7.3% of patients with ARF not requiring renal replacement therapy, 13.2% of patients with ARF on renal replacement therapy (P= 0.02 for trend), and for nasogastric tube obstruction: 0.0%, 5.9%, 14%, respectively (P < 0.001). Gastrointestinal complications were the most frequent cause of suboptimal delivery; the ratio of administered to prescribed daily volume was well above 90% in all the three groups. Definitive withdrawal of enteral nutrition due to complications was documented in 6.1%, 13.2%. and 14.9% of patients, respectively (P= 0.09 for trend). At regimen, mean delivered nonprotein calories were 19.8 kcal/kg (SD 4.6), 22.6 kcal/kg (8.4), 23.4 kcal/kg (6.5); protein intake was 0.92 g/kg (0.21), 0.87 g/kg (0.25), and 0.92 g/kg (0.21), the latter value being below that currently recommended for ARF patients on renal replacement therapy. Median fluid intake with enteral nutrition was 1440 mL (range 720 to 1960), 1200 (720 to 2400), and 960 (360 to 1920). CONCLUSION: Enteral nutrition is a safe and effective nutritional technique to deliver artificial nutrition in ARF patients. Parenteral amino acid supplementation may be required, especially in patients with ARF needing renal replacement therapy.


Assuntos
Injúria Renal Aguda/dietoterapia , Ingestão de Energia , Nutrição Enteral , APACHE , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Nutrição Enteral/efeitos adversos , Nutrição Enteral/métodos , Feminino , Gastroenteropatias/etiologia , Humanos , Masculino , Doenças Metabólicas/etiologia , Pessoa de Meia-Idade , Desnutrição Proteico-Calórica/dietoterapia , Desnutrição Proteico-Calórica/prevenção & controle , Terapia de Substituição Renal
12.
J Rheumatol ; 30(3): 618-21, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12610825

RESUMO

Churg-Strauss syndrome (CSS) and Wegener's granulomatosis (WG) are uncommon primary vasculitides, characterized by the involvement of the small to medium size vessels and by the frequent presence of serum antineutrophil cytoplasmic antibodies (ANCA). The pathogenesis of ANCA associated vasculitides is unclear, but roles for both genetic and environmental factors have been suggested. Familial cases of WG, but not CSS, have been reported. We describe the occurrence of CSS in a man and, 5 years later, WG in his son. These patients live together in an urban area of Northern Italy and share the HLA haplotype A*03; B*07; C*w07; DRB 1*0404, DQB 1*0302. To our knowledge, this is the first report of the familial clustering of CSS and WG in first-degree relatives.


Assuntos
Síndrome de Churg-Strauss/genética , Família , Granulomatose com Poliangiite/genética , Adulto , Anticorpos Anticitoplasma de Neutrófilos/sangue , Síndrome de Churg-Strauss/imunologia , Granulomatose com Poliangiite/imunologia , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade
14.
Arthritis Rheum ; 46(6): 1595-601, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12115191

RESUMO

OBJECTIVE: Fibroblast activation is a crucial event in the development of systemic sclerosis (SSc). Antifibroblast autoantibodies (AFAs), detectable in the sera of SSc patients, are able to induce a proinflammatory phenotype on cultured fibroblasts. This study was undertaken to investigate the mechanisms of the interaction between AFAs and living fibroblasts. METHODS: We coupled to fluorescein 1) IgG purified from AFA-positive and AFA-negative SSc sera (as assessed by cellular enzyme-linked immunosorbent assay) and 2) single healthy donor and pooled normal IgG. The interaction of IgG with living cultured fibroblasts from healthy individuals and from a patient with SSc was visualized by real-time confocal microscopy. Intracellular colocalization of caveolin and internalized AFA-positive IgG was assessed by immunofluorescence. RESULTS: AFA-positive IgG bound to living fibroblasts and was internalized with a cytoplasmic fibrillar pattern, in contrast to AFA-negative IgG. In the IgG tested, no correlation with antinuclear antibody activity was found. Preincubation of fibroblasts with normal IgG did not affect internalization. Internalized AFA-positive IgG colocalized with caveolin, and internalization was entirely inhibited by disassembling fibroblast caveolae with filipin. CONCLUSION: The finding that both normal and pathologic fibroblasts specifically internalized AFA-positive, but not AFA-negative, IgG demonstrates that AFAs in SSc patient sera interact with constitutively expressed membrane molecules on fibroblasts, via an Fc-independent mechanism. The results of colocalization and inhibition experiments suggest that microdomains containing caveolin are involved in the interaction between AFAs and fibroblasts. These data, together with the reported ability of AFAs to activate fibroblasts, provide evidence for a role of AFAs in the pathogenesis of SSc.


Assuntos
Autoanticorpos/metabolismo , Caveolinas/metabolismo , Fibroblastos/imunologia , Fibroblastos/metabolismo , Escleroderma Sistêmico/imunologia , Adulto , Idoso , Autoanticorpos/farmacologia , Caveolina 1 , Células Cultivadas , Meios de Contraste/farmacocinética , Feminino , Fibroblastos/citologia , Fluoresceína/farmacocinética , Humanos , Imunoglobulina G/metabolismo , Imunoglobulina G/farmacologia , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Escleroderma Sistêmico/metabolismo
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