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A myopericytoma in the auricle is rare. If an auricle contains a large, firm, red-brown mass, excision should be considered because the mass may be a myopericytoma. After excision, histopathological and immunohistochemical diagnoses are essential to rule out malignancy. Long-term follow-up is required because the tumor is slow-growing.
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Neoplasias , HumanosAssuntos
Pavilhão Auricular , Ceratose Seborreica , Orelha Externa , Humanos , Ceratose Seborreica/diagnóstico , NarizRESUMO
AIMS: Oxidative stress has been considered to contribute to the development of obesity-related metabolic disorders including insulin resistance. To the contrary, deficiency of an anti-oxidizing enzyme, glutathione peroxidase (GPx)-1, was reported to enhance insulin signaling, suggesting that oxidative stress may inhibit the development of type 2 diabetes. However, the beneficial effects of the absence of GPx-1 in metabolic homeostasis, including body weight control, have not yet been clearly manifested. To clarify the relationship between oxidative stress and obesity-related metabolic disorders, we investigated another mouse deficient with both GPx-1 and catalase (Cat). METHODS: C57BL/6J wild-type and GPx-1-/- × Cat-/- mice were fed with a high-fat diet (60% fat) or a normal chow diet for 16 weeks and were investigated for metabolic and histological studies. RESULTS: Body weight gain was significantly reduced, and glucose metabolism as well as hepatic steatosis was obviously improved in the GPx-1-/- × Cat-/- mice. The serum levels of insulin and total cholesterol were also significantly lowered. For the underlying mechanism, inflammation was attenuated and expression of markers for fat browning was enhanced in the visceral white adipose tissues. CONCLUSIONS: Oxidative stress due to deficiency of GPx-1 and Cat may improve obesity-related metabolic disorders through attenuation of inflammation and fat browning.
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Catalase/genética , Diabetes Mellitus Tipo 2/enzimologia , Glutationa Peroxidase/genética , Animais , Catalase/metabolismo , Colesterol/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Glutationa Peroxidase/deficiência , Humanos , Insulina/metabolismo , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/enzimologia , Obesidade/genética , Obesidade/metabolismo , Estresse Oxidativo , Glutationa Peroxidase GPX1RESUMO
BACKGROUND: The nature of immunoglobulin M (IgM) nephropathy has been controversial for a long time, but it is now considered an independent disease like immunoglobulin A nephropathy. IgM nephropathy has been known to have various clinical manifestations ranging from asymptomatic hematuria and/or proteinuria to nephrotic syndrome. Recently, one case of IgM nephropathy manifesting as crescentic glomerulonephritis (GN) was reported in a child. CASE PRESENTATION: We experienced a case of IgM nephropathy that manifested clinically as nephritic and nephrotic syndrome with pathologically confirmed crescentic GN in a 30-year-old woman. We administered a calcineurin inhibitor and corticosteroids to treat the ongoing nephrotic syndrome after remission of crescentic GN. As a result, her proteinuria was significantly reduced and edema improved. CONCLUSIONS: We described a case of IgM nephropathy in an adult patient who initially developed crescentic GN with nephritic and nephrotic syndrome. This case report could contribute to a deeper understanding of IgM nephropathy.
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Glomerulonefrite/diagnóstico , Imunoglobulina M , Síndrome Nefrótica/diagnóstico , Proteinúria/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Taxa de Filtração Glomerular/fisiologia , Glomerulonefrite/complicações , Humanos , Imunoglobulina M/análise , Síndrome Nefrótica/complicações , Proteinúria/complicaçõesRESUMO
BACKGROUND: Multicentric carpotarsal osteolysis syndrome (MCTO) is characterized by progressive destruction and disappearance of the carpal and tarsal bones associated with nephropathy. MCTO is caused by loss-of-function mutations in the MAF bZIP transcription factor B (MAFB) gene. CASE PRESENTATION: This report describes three unrelated patients with MAFB mutations, including two male and one female patient. Osteolytic lesions in the carpal and tarsal bones were detected at 2 years, 12 years, and 14 months of age, respectively. Associated proteinuria was noted at 4 years, 12 years, and 3 months of age, respectively. Kidney biopsy was performed in two of them and revealed focal segmental glomerulosclerosis (FSGS). One patient showed progression to end-stage renal disease, that is by 1 year after the detection of proteinuria. The second patient had persistent proteinuria but maintained normal renal function. In the third patient, who did not undergo a kidney biopsy, the proteinuria disappeared spontaneously. The bony lesions worsened progressively in all three patients. Mutational study of MAFB revealed three different mutations, two novel mutations [c.183C > A (p.Ser61Arg) and c.211C > G (p.Pro71Ala)] and one known mutation [c.212C > T (p.Pro71Leu)]. CONCLUSION: We report three cases with MCTO and two novel MAFB mutations. The renal phenotypes were different among the three patients, whereas progressive worsening of the bony lesions was common in all patients. We also confirmed FSGS to be an early renal pathologic finding in two cases. A diagnosis of MCTO should be considered in patients with progressive bone loss concentrated primarily in the carpal and tarsal bones and kidney involvement, such as proteinuria.
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Glomerulosclerose Segmentar e Focal/genética , Mutação com Perda de Função , Fator de Transcrição MafB/genética , Osteólise/genética , Proteinúria/genética , Adolescente , Sequência de Bases , Ossos do Carpo/metabolismo , Ossos do Carpo/patologia , Pré-Escolar , Análise Mutacional de DNA , Progressão da Doença , Feminino , Expressão Gênica , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/metabolismo , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Rim/metabolismo , Rim/patologia , Fator de Transcrição MafB/metabolismo , Masculino , Osteólise/complicações , Osteólise/metabolismo , Osteólise/patologia , Proteinúria/complicações , Proteinúria/metabolismo , Proteinúria/patologia , Ossos do Tarso/metabolismo , Ossos do Tarso/patologia , Adulto JovemRESUMO
Proteinuria is a major determinant of adverse renal outcome, and its reduction slows renal progression in glomerular diseases. However, the optimal target of proteinuria in glomerular diseases is unclear, and discrepancies in the definition of proteinuria produce ambiguous findings. Here we investigated the optimal target of proteinuria by using different definitions of proteinuria. We analyzed 574 IgA nephropathy (IgAN), 175 membranous nephropathy (MGN), and 177 focal segmental glomerulosclerosis (FSGS) cases from 3 Korean kidney centers. We evaluated the impact of proteinuria on renal outcome with 2 definitions: time-average proteinuria (TAP) and time-varying proteinuria (TVP). The endpoint was renal progression, defined as a 50% decline in glomerular filtration rate or end-stage renal disease. During a median follow-up of 57.3 months, the primary outcome occurred in 54 patients with IgAN, 26 with MGN, and 30 with FSGS. Multivariate Cox regression using TAP indicated that there was a linear association between proteinuria and risk of renal progression in IgAN. However, moderate proteinuria was not associated with an increased risk of renal progression in MGN and FSGS. In contrast, the analysis by TVP showed that the risk significantly increased in proportion to proteinuria during follow-up in all 3 diseases. Our findings suggest that TVP-based model can delineate association between proteinuria and risk of renal progression better than TAP-based model, considering that TVP reflects the dynamic change of proteinuria over time. Thus, proteinuria reduction to the lowest possible level is required to improve renal outcomes in patients with glomerular diseases.
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Glomerulonefrite/diagnóstico , Proteinúria/diagnóstico , Proteinúria/etiologia , Adulto , Idoso , Diagnóstico Diferencial , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite/complicações , Glomerulonefrite/mortalidade , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Hyperbaric oxygen (HBO2) therapy is currently used for the treatment of chronic wounds, radiation-induced soft tissue necrosis, several oxygen-deficiency conditions and decompression sickness. In addition to the current indications, much empirical and experimental data suggest that HBO2 therapy may benefit autoimmune diseases by suppressing immunity, but the underlying mechanism is not well understood. Therefore, in the present study, we investigated whether HBO2 prevents the development of collagen-induced arthritis (CIA) in association with alteration of the immune balance between pro-inflammatory Th17 and anti-inflammatory regulatory T cells (Tregs). Arthritis was induced in DBA/1 mice by intradermal injection of type II collagen. Animals received either no treatment or 90 minutes of HBO2 (100% oxygen, at 2.0 ATA) daily beginning three days prior to the injection and were monitored for the development of arthritis. Six weeks later, joint tissues and spleens were analyzed for the alteration of immune balance between Th17 and Tregs by immunohistochemistry (IHC) or Western blot. Injection of collagen-induced extensive arthritis and extramedullary hematopoiesis in the spleens. Meanwhile, joint swelling and inflammatory tissue damages as well as extramedullary hematopoiesis were significantly less severe in the mice treated with HBO2. Both IHC and Western blot showed a decrease of FOXP3 and an increase of pSTAT3 expressions in the joints and spleens of the mice injected with collagen. This suggested that the systemic immune balance was biased toward Th17 cells, which was reversed by HBO2 therapy. These results suggested acute CIA associated with an immune balance favoring Th17 was attenuated by HBO2 in parallel with restoration of the immune balance to favor Tregs.
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Artrite Experimental/prevenção & controle , Hematopoese Extramedular , Oxigenoterapia Hiperbárica , Linfócitos T Reguladores/citologia , Animais , Artrite Experimental/induzido quimicamente , Colágeno Tipo II , Fatores de Transcrição Forkhead/metabolismo , Imunidade Celular , Masculino , Camundongos , Camundongos Endogâmicos DBA , Fator de Transcrição STAT3/metabolismo , Baço , Células Th17/citologiaRESUMO
BACKGROUND: The Oxford classification has been widely used in IgA nephropathy. However, its clinical usefulness of determining immunosuppression is unknown. AIM: Whether the Oxford classification could predict the development of proteinuria ≥1 g/g Cr and worsening kidney function, as well as the clinical efficacy of corticosteroid treatment according to each histologic variable of the Oxford-MEST. METHODS: We included 377 patients with early-stage IgA nephropathy. The study endpoints were the development of a heavy proteinuria and a decline renal function. RESULTS: The results showed that among the Oxford-MEST lesions, only M1 predicted the risk of the development of proteinuria ≥1.0 g/g Cr compared to other lesions in a time-varying Cox model adjusted for multiple confounding factors. In addition, the risk of reaching a 30% decline in eGFR was significantly higher in patients with M1 than in those with M0. Furthermore, patients with M1 had a greater decline of eGFR than patients with M0. However, steroid treatment in M1 lesion was not associated with improving clinical outcomes in the unmatched and propensity score matched cohort. CONCLUSIONS: This finding may provide a rationale for using the Oxford classification as a guidance to initiate immunosuppression in the early stages of IgA nephropathy. KEY MESSAGES M1 has independently predictive role among the Oxford lesions in IgA nephropathy. Oxford classification should be defined during pathologic approach. Decision of starting immunosuppression according to the Oxford lesions.
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Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/uso terapêutico , Proteinúria/tratamento farmacológico , Adulto , Biomarcadores/metabolismo , Tomada de Decisão Clínica , Ensaios Clínicos como Assunto , Progressão da Doença , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomerulonefrite por IGA/classificação , Glomerulonefrite por IGA/patologia , Glucocorticoides/uso terapêutico , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteinúria/complicações , Proteinúria/urina , Insuficiência Renal/complicações , Insuficiência Renal/prevenção & controleRESUMO
BACKGROUND/AIMS: Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day. METHODS: Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy. RESULTS: Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was -41.3% ± 26.1% (p < 0.001) in the regular-dose group and -21.1% ± 45.1% (p = 0.005) in the low-dose group. In the low-dose group, blood pressure was constant throughout the study period, and there was no symptomatic hypotension. In the regular-dose group, blood pressure decreased at weeks 8 and 12. No significant change in glomerular filtration rate, serum creatinine level, or serum potassium level was observed during the study period. CONCLUSIONS: Our results suggest that low-dose valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.
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Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Glomerulonefrite por IGA/tratamento farmacológico , Proteinúria/tratamento farmacológico , Valsartana/administração & dosagem , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Biomarcadores/urina , Pressão Sanguínea , Creatinina/urina , Feminino , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/fisiopatologia , Glomerulonefrite por IGA/urina , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteinúria/diagnóstico , Proteinúria/fisiopatologia , Proteinúria/urina , República da Coreia , Fatores de Tempo , Resultado do Tratamento , Valsartana/efeitos adversosRESUMO
We report a case of a 61-year-old female with atypical chest pain. The chest CT scan revealed a well-circumscribed large intrapulmonary nodule that showed vigorous and homogeneous contrast enhancement. The nodule was diagnosed as a meningioma after surgery. Metastatic meningioma was excluded by brain and spine MRI scans. Primary pulmonary meningioma usually appears as a solitary well-defined round or lobulated nodule with variable enhancement on CT; this case is unique because of the intense and homogeneous enhancement. Although rare, primary pulmonary meningioma should be considered in the differential diagnosis of a well-defined pulmonary nodule with dense and homogeneous enhancement.
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Neoplasias Pulmonares/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Neoplasias Pulmonares/cirurgia , Meningioma/cirurgia , Pessoa de Meia-Idade , Intensificação de Imagem Radiográfica , Tomografia Computadorizada por Raios XRESUMO
Solitary fibrous tumor (SFT) is a rare neoplasm of mesenchymal origin, especially in the central nervous system (CNS). Reported herein is a case of SFT of CNS in a 63-year-old female patient who had confused mentality, without other neurological deficit. The brain MRI showed an ovoid mass in the right frontal lobe. The tumor was surgically removed grossly and totally, and the pathologic diagnosis was SFT. At 55 months after the surgery, the tumor recurred at the primary site and at an adjacent area. A second operation was thus done, and the tumor was again surgically removed grossly and totally. The pathologic diagnosis was the same as the previous, but the Ki-67 index was elevated. Ten months later, two small recurring tumors in the right frontal skull base were found in the follow-up MRI. It was decided that radiation therapy be done, and MRI was done again 3 months later. In the follow-up MRI, the size of the recurring mass was found to have decreased, and the patient did not manifest any significant symptom. Follow-up will again be done 18 months after the second surgery.
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The olfactory groove schwannoma is a quite rare tumor. We report a case of a 49-year-old woman with an olfactory groove schwannoma attached to the cribriform plate without olfactory dysfunction. She had no specific neurological symptoms other than a headache, and resection of the tumor showed it to be a schwannoma. About 19 months after the operation, a follow-up MRI showed no evidence of tumor recurrence. Surgical resection through subfrontal approach could be one of the curative modality in managing an olfactory groove schwannoma. An olfactory groove schwannoma should be considered in the differential diagnosis of anterior skull base tumors.
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BACKGROUND: In chronic wounds, especially burn scars, malignant tumors can arise. However, it is rare for a subacute burn injury to change to a malignant lesion within one month. Moreover, a case of squamous cell carcinoma arising from HeNe laser therapy after a chemical burn has never been reported. CASE REPORT: In this report, we examine a rare case of squamous cell carcinoma arising from HeNe laser therapy after a chemical burn. Because pathologic investigations were made from the first operation, both early detection of the squamous cell carcinoma and consideration of the HeNe laser therapy as a risk factor for the skin cancer were possible. The cancer was completely removed and reconstruction of the defect was successfully achieved in a timely manner. CONCLUSION: Although there has as yet been no reported case of squamous cell carcinoma induced by laser therapy, it is important for clinicians to recognize both the possibility of laser-induced cancer and the rapid change of cancer, so they can provide appropriate and timely treatment.
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Queimaduras Químicas/complicações , Carcinoma de Células Escamosas/etiologia , Terapia a Laser/efeitos adversos , Neoplasias Cutâneas/etiologia , Cicatrização/efeitos da radiação , Queimaduras Químicas/radioterapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Hipoclorito de Sódio/efeitos adversosRESUMO
Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting from excessive stimulation of immune cells. Traditionally, reactive oxygen species (ROS) have been implicated in the progression of inflammatory diseases, but several opposing observations suggest the protective role of ROS in inflammatory disease. Recently, we demonstrated ROS prevented imiquimod-induced psoriatic dermatitis through enhancing regulatory T cell function. Thus, we hypothesized AD might also be attenuated in elevated levels of ROS through tissue hyperoxygenation, such as by hyperbaric oxygen therapy (HBOT) or applying an oxygen-carrying chemical, perfluorodecalin (PFD). Elevated levels of ROS in the skin have been demonstrated directly by staining with dihydroethidum as well as indirectly by immunohistochemistry (IHC) for indoleamine 2,3-dioxygenase (IDO). A murine model of AD was developed by repeated application of a chemical irritant (1% 2,4-dinitrochlorobenzene) and house dust mite (Dermatophagoide farinae) extract on one ear of BALB/c mice. The results showed treatment with HBOT or PFD significantly attenuated AD, comparably with 0.1% prednicarbate without any signs of side effects, such as telangiectasia. The expressions of interleukin-17A and interferon-γ were also decreased in the AD lesions by treatment with HBOT or PFD. Enhanced expression of IDO and reduced level of hypoxia-inducible factor-1α, in association with increased frequency of FoxP3+ regulatory T cells in the AD lesions, might be involved in the underlying mechanism of oxygen therapy. Taken together, it was suggested that tissue hyperoxygenation, by HBOT or treatment with PFD, might attenuate AD through enhancing skin ROS level.
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Dermatite Atópica/patologia , Dermatite Atópica/terapia , Fluorocarbonos/uso terapêutico , Oxigenoterapia Hiperbárica , Oxigênio/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Pele/patologia , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/metabolismo , Dinitroclorobenzeno , Modelos Animais de Doenças , Fluorocarbonos/administração & dosagem , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oxigênio/administração & dosagem , Pyroglyphidae/química , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
BACKGROUND: Proteinuria is a target for renoprotection in kidney diseases. However, optimal level of proteinuria reduction in IgA nephropathy (IgAN) is unknown. METHODS: We conducted a retrospective observational study in 500 patients with biopsy-proven IgAN. Time-averaged proteinuria (TA-P) was calculated as the mean of every 6 month period of measurements of spot urine protein-to-creatinine ratio. The study endpoints were a 50% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease (ESRD), and slope of eGFR. RESULTS: During a median follow-up duration of 65 (12-154) months, a 50% decline in eGFR occurred in 1 (0.8%) patient with TA-P of <0.3 g/g compared to 6 (2.7%) patients with TA-P of 0.3-0.99 g/g (hazard ratio, 2.82; Pâ=â0.35). Risk of reaching a 50% decline in eGFR markedly increased in patients with TA-P of 1.0-2.99 g/g (Pâ=â0.002) and those with TA-P≥3.0 g/g (P<0.001). ESRD did not occur in patients with TA-P<1.0 g/g compared to 26 (20.0%) and 8 (57.1%) patients with TA-P of 1.0-2.99 and ≥3.0 g/g, respectively. Kidney function of these two groups deteriorated faster than those with TA-P<1.0 g/g (P<0.001). However, patients with TA-P of 0.3-0.99 g/g had a greater decline of eGFR than patients with TA-P<0.3 g/g (-0.41±1.68 vs. -0.73±2.82 ml/min/1.73 m2/year, Pâ=â0.03). CONCLUSION: In this study, patients with TA-P<1.0 g/g show favorable outcomes. However, given the faster eGFR decline in patients with TA-P of 0.3-0.99 g/g than in patients with TA-P<0.3 g/g, the ultimate optimal goal of proteinuria reduction can be lowered in the management of IgAN.
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Glomerulonefrite por IGA/urina , Proteinúria/urina , Adulto , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/mortalidade , Glomerulonefrite por IGA/terapia , Humanos , Estimativa de Kaplan-Meier , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Proteinúria/mortalidade , Proteinúria/terapia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Reactive oxygen species (ROS) have been implicated in the progression of inflammatory diseases including inflammatory bowel diseases (IBD). Meanwhile, several studies suggested the protective role of ROS in immune-mediated inflammatory diseases, and it was recently reported that dextran sodium sulfate (DSS)-induced colitis was attenuated in mice with an elevated level of ROS due to deficiency of peroxiredoxin II. Regulatory T cells (Tregs) are critical in the prevention of IBD and Treg function was reported to be closely associated with ROS level, but it has been investigated only in lowered levels of ROS so far. In the present study, in order to clarify the relationship between ROS level and Treg function, and their role in the pathogenesis of IBD, we investigated mice with an elevated level of ROS due to deficiency of both glutathione peroxidase (GPx)-1 and catalase (Cat) for the susceptibility of DSS-induced colitis in association with Treg function. The results showed that DSS-induced colitis was attenuated and Tregs were hyperfunctional in GPx1-/- × Cat-/- mice. In vivo administration of N-acetylcysteine (NAC) aggravated DSS-induced colitis and decreased Treg function to the level comparable to WT mice. Attenuated Th17 cell differentiation from naïve CD4+ cells as well as impaired production of IL-6 and IL-17A by splenocytes upon stimulation suggested anti-inflammatory tendency of GPx1-/- × Cat-/- mice. Suppression of Stat3 activation in association with enhancement of indoleamine 2,3-dioxygenase and FoxP3 expression might be involved in the immunosuppressive mechanism of GPx1-/- × Cat-/- mice. Taken together, it is implied that ROS level is critical in the regulation of Treg function, and IBD may be attenuated in appropriately elevated levels of ROS.
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Catalase/metabolismo , Colite/enzimologia , Glutationa Peroxidase/metabolismo , Linfócitos T Reguladores/metabolismo , Acetilcisteína/uso terapêutico , Animais , Catalase/genética , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Sulfato de Dextrana/toxicidade , Glutationa Peroxidase/genética , Masculino , Camundongos , Camundongos Knockout , Glutationa Peroxidase GPX1RESUMO
BACKGROUND: Many studies have shown that clinical characteristics and outcomes differ depending on pathologic variants of focal segmental glomerulosclerosis (FSGS). However, these are not well defined in Asian populations. METHODS: This retrospective study evaluated clinical features and outcomes of pathologic FSGS variants in 111 adult patients between January 2004 and December 2012. Primary outcome was the composite of doubling of baseline serum creatinine concentrations (D-SCr) or onset of end-stage renal disease (ESRD). Secondary outcome included complete (CR) or partial remission (PR). RESULTS: There were 70 (63.1%), 20 (18.0%), 17 (15.3%), 3 (2.7%), and 1 (0.9%) patients with not-otherwise specified (NOS), tip, perihilar, cellular, and collapsing variants, respectively. At presentation, nephrotic-range proteinuria occurred more commonly in tip lesion than in other variants. The overall 5-year renal survival rate was 76.8%. During a median follow-up of 34.5 months, only 1 (5.0%) patient with a tip lesion reached the composite end point compared to 2 (11.8%) and 12 (17.1%) patients in perihilar and NOS variants, but this difference was not statistically significant in an adjusted Cox model. However, tip lesion was associated with a significantly increased probability of achieving CR (P = 0.044). CONCLUSION: Similar to other populations, Korean adult patients with FSGS have distinct clinical features with the exception of a rare frequency of cellular and collapsing variants. Although pathologic variants were not associated with overall outcome, the tip variant exhibited favorable outcome in terms of achieving remission. Further studies are required to delineate long-term outcome and response to treatment of the pathologic variants.
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Povo Asiático , Creatinina/sangue , Glomerulosclerose Segmentar e Focal/etnologia , Glomerulosclerose Segmentar e Focal/patologia , Idade de Início , Biomarcadores/sangue , Comorbidade , Feminino , Glomerulosclerose Segmentar e Focal/sangue , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Incidência , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etnologia , Falência Renal Crônica/prevenção & controle , Masculino , Pessoa de Meia-Idade , Proteinúria/epidemiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Psoriasis is a chronic inflammatory skin disease resulting from immune dysregulation. Regulatory T cells (Tregs) are important in the prevention of psoriasis. Traditionally, reactive oxygen species (ROS) are known to be implicated in the progression of inflammatory diseases, including psoriasis, but many recent studies suggested the protective role of ROS in immune-mediated diseases. In particular, severe cases of psoriasis vulgaris have been reported to be successfully treated by hyperbaric oxygen therapy (HBOT), which raises tissue level of ROS. Also it was reported that Treg function was closely associated with ROS level. However, it has been only investigated in lowered levels of ROS so far. Thus, in this study, to clarify the relationship between ROS level and Treg function, as well as their role in the pathogenesis of psoriasis, we investigated imiquimod-induced psoriatic dermatitis (PD) in association with Treg function both in elevated and lowered levels of ROS by using knockout mice, such as glutathione peroxidase-1(-/-) and neutrophil cytosolic factor-1(-/-) mice, as well as by using HBOT or chemicals, such as 2,3-dimethoxy-1,4-naphthoquinone and N-acetylcysteine. The results consistently showed Tregs were hyperfunctional in elevated levels of ROS, whereas hypofunctional in lowered levels of ROS. In addition, imiquimod-induced PD was attenuated in elevated levels of ROS, whereas aggravated in lowered levels of ROS. For the molecular mechanism that may link ROS level and Treg function, we investigated the expression of an immunoregulatory enzyme, indoleamine 2,3-dioxygenase (IDO) which is induced by ROS, in PD lesions. Taken together, it was implied that appropriately elevated levels of ROS might prevent psoriasis through enhancing IDO expression and Treg function.
Assuntos
Aminoquinolinas/efeitos adversos , Dermatite/imunologia , Psoríase/induzido quimicamente , Psoríase/imunologia , Espécies Reativas de Oxigênio/metabolismo , Linfócitos T Reguladores/imunologia , Acetilcisteína/administração & dosagem , Acetilcisteína/efeitos adversos , Animais , Dermatite/complicações , Dermatite/patologia , Progressão da Doença , Glutationa Peroxidase/deficiência , Glutationa Peroxidase/metabolismo , Oxigenoterapia Hiperbárica , Imiquimode , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Camundongos Endogâmicos C57BL , NADPH Oxidases/deficiência , NADPH Oxidases/metabolismo , Naftoquinonas/farmacologia , Psoríase/complicações , Psoríase/patologia , Linfócitos T Reguladores/efeitos dos fármacos , Glutationa Peroxidase GPX1RESUMO
Pathologic features can provide valuable information for determining prognosis in IgA nephropathy (IgAN). However, it is uncertain whether the Oxford classification, a new classification of IgAN, can predict renal outcome better than previous ones. We conducted a retrospective cohort study in 500 patients with biopsy-proven IgAN between January 2002 and December 2010 to compare the ability of the Haas and the Oxford classifications to predict renal outcome. Primary outcome was a doubling of the baseline serum creatinine concentration (D-SCr). During a mean follow-up of 68 months, 52 (10.4%) and 35 (7.0%) developed D-SCr and end-stage renal disease, respectively. There were graded increases in the development of D-SCr in the higher Haas classes. In addition, the primary endpoint of D-SCr occurred more in patients with the Oxford M and T lesions than those without such lesions. In multivariate Cox regression analyses, the Haas class V (HR, 12.19; P=.002) and the Oxford T1 (hazard ratio [HR], 6.68; P<.001) and T2 (HR, 12.16; P<.001) lesions were independently associated with an increased risk of reaching D-SCr. Harrell's C index of each multivariate model with the Haas and the Oxford classification was 0.867 (P=.015) and 0.881 (P=.004), respectively. This was significantly higher than that of model with clinical factors only (C=0.819). However, there was no difference in C-statistics between the 2 models with the Haas and the Oxford classifications (P=.348). This study suggests that the Haas and the Oxford classifications are comparable in predicting progression of IgAN.
Assuntos
Glomerulonefrite por IGA/classificação , Glomerulonefrite por IGA/complicações , Falência Renal Crônica/etiologia , Adulto , Creatinina/sangue , Progressão da Doença , Feminino , Glomerulonefrite por IGA/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
Glomerulonephritis occurs as a rare form of renal manifestation in Plasmodium falciparum malaria. Herein, we report a case of falciparum malaria-associated IgA nephropathy for the first time. A 49-yr old male who had been to East Africa was diagnosed with Plasmodium falciparum malaria. Microhematuria and proteinuria along with acute kidney injury developed during the course of the disease. Kidney biopsy showed mesangial proliferation and IgA deposits with tubulointerstitial inflammation. Laboratory tests after recovery from malaria showed disappearance of urinary abnormalities and normalization of kidney function. Our findings suggest that malaria infection might be associated with IgA nephropathy.