RESUMO
We wanted to analyze whether tumor HLA class I (HLA-I) expression influences the pattern of the immune cell infiltration and stromal cell reaction in the tumor microenvironment. Tumor tissues obtained from 57 patients diagnosed with lung carcinomas were analyzed for HLA expression and leukocyte infiltration. 28 patients out of the 57 were completely negative for HLA-I expression (49.1%) or showed a selective HLA-A locus downregulation (three patients, 5.2%). In 26 out of 57 tumors (47.8%) we detected a positive HLA-I expression but with a percentage of HLA-I negative cells between 10 and 25%. The HLA-I negative phenotype was produced by a combination of HLA haplotype loss and a transcriptional downregulation of ß2-microglobulin (ß2-m) and LMP2 and LMP7 antigen presentation machinery genes. The analysis and localization of different immune cell populations revealed the presence of two major and reproducible patterns. One pattern, which we designated "immune-permissive tumor microenvironment (TME)," was characterized by positive tumor HLA-I expression, intratumoral infiltration with cytotoxic T-CD8+ cells, M1-inflammatory type macrophages, and a diffuse pattern of FAP+ cancer-associated fibroblasts. In contrast, another pattern defined as "non-immune-permissive TME" was found in HLA-I negative tumors with strong stromal-matrix interaction, T-CD8+ cells surrounding tumor nests, a dense layer of FAP+ fibroblasts and M2/repair-type macrophages. In conclusion, this study revealed marked differences between HLA class I-positive and negative tumors related to tissue structure, the composition of leukocyte infiltration and stromal response in the tumor microenvironment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Genes MHC Classe I , Antígenos HLA/imunologia , Neoplasias Pulmonares/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T Citotóxicos/imunologia , Evasão Tumoral , Microambiente Tumoral/imunologia , Idoso , Idoso de 80 Anos ou mais , Apresentação de Antígeno , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular , Progressão da Doença , Regulação para Baixo , Endopeptidases , Feminino , Fibroblastos/patologia , Gelatinases/análise , Antígenos HLA/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Macrófagos/patologia , Masculino , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Serina Endopeptidases/análise , Evasão Tumoral/genética , Evasão Tumoral/imunologiaRESUMO
AIMS: Immunohistochemistry is a highly valuable and widely used tool in the subtyping of lung carcinomas. The aim of this study was to identify markers for the differential diagnosis of non-small-cell carcinomas. METHODS AND RESULTS: We report on the immunohistochemical localization of plakophilin-1 (PKP1), keratin-15 (KRT15) and desmoglein-3 (DSG3) intercellular adhesion proteins in samples from 75 primary non-small-cell lung cancers in non-treated patients. The staining pattern of these proteins differed between squamous cell carcinomas and adenocarcinomas, with no membrane staining in the latter. Membrane staining for all three proteins was characteristic of squamous cell carcinomas. We observed a relationship between the presence/absence of these proteins in the membranes of squamous cell carcinomas and the differentiation grade, with more intense staining in better differentiated areas. CONCLUSIONS: Staining for these proteins marked intercellular junctions that are characteristic of stratified squamous epithelium and of neoplasias with this type of differentiation, and can be useful in the diagnosis of patients with squamous cell carcinoma of the lung. The high specificity of membrane staining for PKP1 and DSG3 and high sensitivity of cytoplasmic and membrane staining for KRT15 for the diagnosis of squamous cell carcinoma may be useful for the differential diagnosis of non-small-cell carcinomas.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Desmogleína 3/metabolismo , Desmossomos/patologia , Queratina-15/metabolismo , Neoplasias Pulmonares/patologia , Placofilinas/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Diferenciação Celular , Desmossomos/metabolismo , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismoRESUMO
We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN) and other renal lesions related to prolonged cold ischemia/reperfusion (IR) in kidneys preserved at 4°C in University of Wisconsin (UW) solution. Material and Methods. We used 30 male Parp1(+/+) wild-type and 15 male Parp1(0/0) knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone (DPQ) at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ). We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp1(0/0) knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.
Assuntos
Isquemia/patologia , Rim/irrigação sanguínea , Inibidores de Poli(ADP-Ribose) Polimerases , Traumatismo por Reperfusão/prevenção & controle , Animais , Western Blotting , Temperatura Baixa , Isoquinolinas/farmacologia , Rim/patologia , Rim/ultraestrutura , Necrose Tubular Aguda/patologia , Necrose Tubular Aguda/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica , Piperidinas/farmacologia , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/fisiologia , Traumatismo por Reperfusão/patologiaRESUMO
The development of reliable gene expression profiling technology is having an increasing impact on our understanding of lung cancer biology. Our study aimed to determine any correlation between the phenotypic heterogeneity and genetic diversity of lung cancer. Microarray analysis was performed on a set of 46 tumor samples and 45 paired nontumor samples of nonsmall cell lung cancer (NSCLC) samples to establish gene signatures in primary adenocarcinomas and squamous-cell carcinomas, determine differentially expressed gene sequences at different stages of the disease and identify sequences with biological significance for tumor progression. After the microarray analysis, the expression level of 92 selected genes was validated by qPCR and the robust Bonferroni test in an independent set of 70 samples composed of 48 tumor samples and 22 nontumor samples. Gene sequences were differentially expressed as a function of tumor type, stage and differentiation grade. High upregulation was observed for KRT15 and PKP1, which may be good markers to distinguish squamous-cell carcinoma samples. High downregulation was observed for DSG3 in stage IA adenocarcinomas.
Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Perfilação da Expressão Gênica , Neoplasias Pulmonares/genética , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Reprodutibilidade dos TestesRESUMO
Background: An antibody panel is needed to definitively differentiate between adenocarcinoma (AC) and squamous cell carcinoma (SCC) in order to meet more stringent requirements for the histologic classification of lung cancers. Staining of desmosomal plaque-related proteins may be useful in the diagnosis of lung SCC.Materials and methods: We compared the usefulness of six conventional (CK5/6, p40, p63, CK7, TTF1, and Napsin A) and three novel (PKP1, KRT15, and DSG3) markers to distinguish between lung SCC and AC in 85 small biopsy specimens (41 ACs and 44 SCCs). Correlations were examined between expression of the markers and patients' histologic and clinical data.Results: The specificity for SCC of membrane staining for PKP1, KRT15, and DSG3 was 97.4%, 94.6%, and 100%, respectively, and it was 100% when the markers were used together and in combination with the conventional markers (AUCs of 0.7619 for Panel 1 SCC, 0.7375 for Panel 2 SCC, 0.8552 for Panel 1 AC, and 0.8088 for Panel 2 AC). In a stepwise multivariate logistic regression model, the combination of CK5/6, p63, and PKP1 in membrane was the optimal panel to differentiate between SCC and AC, with a percentage correct classification of 96.2% overall (94.6% of ACs and 97.6% of SCCs). PKP1 and DSG3 are related to the prognosis.Conclusions: PKP1, KRT15, and DSG3 are highly specific for SCC, but they were more useful to differentiate between SCC and AC when used together and in combination with conventional markers. PKP1 and DSG3 expressions may have prognostic value.
Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Desmossomos/metabolismo , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/metabolismo , Desmogleína 3/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Queratina-15/metabolismo , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Placofilinas/metabolismo , Prognóstico , Sensibilidade e EspecificidadeRESUMO
The hemophagocytic syndrome is a serious clinical-histological entity secondary to different diseases. Collapsing glomerulonephritis is a proliferative podocytopathy that usually has an unfavorable renal prognosis. We present a case in which both entities were associated, which is an infrequent form of hepatosplenic T-cell lymphoma. In addition, we review the role of the markers of podocyte dedifferentiation in this glomerulopathy and its pathophysiology and treatment.
El síndrome hemofagocítico es una condición clínica e histológica grave, secundaria a diferentes procesos. La glomerulonefritis colapsante es una podocitopatía proliferativa, generalmente de pronóstico desfavorable para la función renal. Se presenta un caso en el que las dos condiciones aparecieron asociadas, lo cual es una forma infrecuente de presentación del linfoma hepatoesplénico de células T. Se discute, asimismo, el papel de los marcadores de desdiferenciación podocitaria en esta glomerulopatía, y se revisan la fisiopatología y el tratamiento.
Assuntos
Desdiferenciação Celular , Glomerulonefrite/patologia , Podócitos/patologia , Glomerulonefrite/complicações , Humanos , Neoplasias Hepáticas/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Linfoma de Células T/complicações , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/complicações , Neoplasias Esplênicas/complicaçõesRESUMO
Immune-checkpoint inhibitors show encouraging results in cancer treatment, but the clinical benefit is limited exclusively to a subset of patients. We analyzed the density and composition of tumor T-cell infiltration in non-small-cell lung carcinoma (NSCLC) in relation to PD-L1 and HLA class I (HLA-I) expression. We found that positive HLA-I expression, independently on PD-L1 status, is the key factor determining the increased density of the immune infiltrate. When both markers were analyzed simultaneously, we identified four phenotypes of HLA-I and PD-L1 co-expression. They demonstrated different patterns of tumor infiltration and clinicopathologic characteristics, including the tumor size and lymphatic spread. All HLA-I+/PD-L1+ tumors had a high degree of intratumoral infiltration with CD8+T-lymphocytes, whereas HLA-I loss was associated with a significantly reduced number of tumor infiltrating T-lymphocytes mostly restrained in the stroma surrounding the tumor nest. HLA-I-negative/PD-L1-positive tumors had bigger size (T) and lower grade of infiltration with CD8+T-cells. It represents a cancer immune escape phenotype that combines two independent mechanisms of immune evasion: loss of HLA-I and upregulation of PD-L1. Using GCH-array analysis of human lung cancer cell lines we found that the loss of heterozygosity (LOH) with complete or partial deletion of HLA-I genes is the principal mechanism of HLA-I alterations. This irreversible defect, which could potentially decrease the clinical efficacy of lung cancer immunotherapy, appears to be underestimated. In conclusion, our results suggest that the analysis of HLA-I is very important for the selection of potential responders to cancer immunotherapy.
RESUMO
The aim of the present study is to analyze the effects of 5-aminoisoquinoline (5-AIQ), a poly(ADP-ribose) polymerase-1 (PARP1) inhibitor, over renal dysfunction and fibrosis during recovery phase of cisplatin (CisPt)-induced acute kidney injury (AKI) in rats. Male Wistar rats were distributed in three groups (n=8 each group): control, CisPt, and CisPt + 5-AIQ. Control and CisPt groups received a subcutaneous injection of either saline or 7 mg/kg CisPt, respectively. CisPt + 5-AIQ group received two intraperitoneal injections of 10 mg/kg 5-AIQ 2 h before and 24 h after CisPt treatment. Thirteen days after the treatment, rats were housed in metabolic cages and 24-h urine collection was made. At day 14, CisPt-treated rats showed increased diuresis, N-acetyl-ß-d-glucosaminidase (NAG) excretion, glucosuria and sodium fractional excretion (NaFE), and decreased creatinine clearance (CrCl). 5-AIQ significantly increased CrCl and decreased NAG excretion, glucosuria, and NaFE. In plasma, CisPt increased sodium, urea, and creatinine concentrations, while 5-AIQ treatment decreased these variables to the levels of control group. 5-AIQ completely prevented the body weight loss evoked by CisPt treatment. CisPt also induced an increased renal expression of PAR polymer, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1), and collagen-IV. These variables were decreased in CisPt + 5-AIQ group. Tubular lesions and renal fibrosis were also decreased by 5-AIQ treatment. We conclude that inhibition of PARP1 with 5-AIQ can attenuate long-term nephrotoxic effects associated with the CisPt treatment, preventing renal dysfunction and body weight decrease and ameliorating tubular lesions and collagen deposition.
Assuntos
Injúria Renal Aguda , Cisplatino/efeitos adversos , Isoquinolinas/farmacologia , Rim , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Animais , Cisplatino/farmacologia , Fibrose , Rim/metabolismo , Rim/patologia , Testes de Função Renal , Masculino , Ratos , Ratos WistarRESUMO
Immune cell infiltration is a common feature of many human solid tumors. Innate and adaptative immune systems contribute to tumor immunosurveillance. We investigated whether tumors evade immune surveillance by inducing states of tolerance and/or through the inability of some immune subpopulations to effectively penetrate tumor nests. Immunohistochemistry and flow cytometry analysis were used to study the composition and distribution of immune subpopulations in samples of peripheral blood, tumor tissue (TT), adjacent tumor tissue (ATT), distant non-tumor tissue (DNTT), cancer nests, cancer stroma, and invasive margin in 61 non-small-cell lung cancer (NSCLC) patients. A significantly higher percentage of T and B cells and significantly lower percentage of NK cells were detected in TT than in DNTT. Memory T cells (CD4+CD45RO+, CD8+CD45RO+) and activated T cells (CD8+DR+) were more prevalent in TT. Alongside this immune activation, the percentage of T cells with immunosuppressive activity was higher in TT than in DNTT. B- cells were practically non-existent in tumor nests and were preferentially located in the invasive margin. The dominant NK cell phenotype in peripheral blood and DNTT was the cytotoxic phenotype (CD56+ CD16+), while the presence of these cells was significantly decreased in ATT and further decreased in TT. Finally, the immunologic response differed between adenocarcinoma and squamous cell carcinoma and according to the tumor differentiation grade. These findings on the infiltration of innate and adaptative immune cells into tumors contribute to a more complete picture of the immune reaction in NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Pulmonares/imunologia , Pulmão/imunologia , Subpopulações de Linfócitos/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Memória Imunológica , Masculino , Pessoa de Meia-IdadeRESUMO
Ataxia-telangiectasia (A-T) is a rare disease characterized by neurodegenerative alterations, telangiectasia, primary immunodeficiency, extreme sensitivity to radiation, and susceptibility to neoplasms. A-T patients have inactivation of ataxia-telangiectasia-mutated (ATM) protein, which controls DNA double-strand break repair and is involved in oxidative stress response, among other functions; dysfunctional control of reactive oxygen species may be responsible for many of the clinical manifestations of this disease. To the best of our knowledge, hepatic lesions of steatohepatitis have not previously been reported in A-T patients. The present study reports the case of a 22-year-old man diagnosed with A-T at the age of 6 years who was referred to our Digestive Disease Unit with a three-year history of hyperlipidemia and liver test alterations. Core liver biopsy showed similar lesions to those observed in nonalcoholic steatohepatitis. Immunohistochemical staining disclosed the absence of ATM protein in hepatocyte nuclei. We suggest that the liver injury may be mainly attributable to the oxidative stress associated with ATM protein deficiency, although other factors may have made a contribution. We propose the inclusion of A-T among the causes of nonalcoholic steatohepatitis, which may respond to antioxidant therapy.
RESUMO
UNLABELLED: The aim of this study was to characterize the morphology and immunophenotype of ganglion cysts (GCs) and explore their histogenetic origin. MATERIAL AND METHODS: A cross-sectional morphological and immunohistochemical study of 354 GCs used the following antibody panel: vimentin, specific actin, ß-actin, smooth-muscle actin, smoothelin, h-caldesmon, ß-catenin, desmin, calponin, podoplanin, keratins 5/6, E-cadherin, cyclooxygenase 2 (COX-2), lysozyme, CD10, CD31, CD33, CD34, CD68, Ki-67, and PCNA. Double-blind semi-quantitative analyses were conducted to evaluate the immunopositivity on a 4-point scale. Samples from 10 synovial membranes and 10 scapholunate ligaments were compared. GCs showed a hyalinized wall with mesenchymal spindle cells and were intensely positive for vimentin, actins, h-caldesmon, calponin in all cases and for podoplanin in 53% of cases, suggesting features of early muscle differentiation, without ruling out a myofibroblastic origin. Focal cavity lining of non-synovial flat or raised cells (CD34/CD31/CD10/E-cadherin-negative and podoplanin-positive in 34% of cases) was detected in 93% of cases, showing differential expression with synovial membrane and scapholunate ligament cells. Nuclear positivity for proliferative markers was observed in GC wall cells (258.1±255; 1019.3±316 positive cells/mm², Ki-67 and PCNA, respectively) but positivity for these markers was significantly lower (p⟨0.001 Mann Whitney U-test) in scapholunate ligament samples. CONCLUSION: In this first immunohistochemical study of GCs, focal cellular lining of the cavity was observed in almost all cases, and the immunophenotype was identical to that of GC wall cells. These cells are immunohistochemically different from synoviocytes and scapholunate ligament cells and show characteristics of myofibroblasts or mesenchymal cells undergoing early muscle differentiation.
Assuntos
Cistos Glanglionares/metabolismo , Cistos Glanglionares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular , Criança , Pré-Escolar , Estudos Transversais , Feminino , Cistos Glanglionares/etiologia , Humanos , Imuno-Histoquímica , Cápsula Articular/metabolismo , Cápsula Articular/patologia , Ligamentos/metabolismo , Ligamentos/patologia , Masculino , Pessoa de Meia-Idade , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Estresse Mecânico , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Adulto JovemRESUMO
Hydroxychloroquine has been shown to be efficacious in the treatment of autoimmune diseases, including systemic lupus erythematosus. Hydroxychloroquine-treated lupus patients showed a lower incidence of thromboembolic disease. Endothelial dysfunction, the earliest indicator of the development of cardiovascular disease, is present in lupus. Whether hydroxychloroquine improves endothelial function in lupus is not clear. The aim of this study was to analyze the effects of hydroxychloroquine on hypertension, endothelial dysfunction, and renal injury in a female mouse model of lupus. NZBWF1 (lupus) and NZW/LacJ (control) mice were treated with hydroxychloroquine 10 mg/kg per day by oral gavage, or with tempol and apocynin in the drinking water, for 5 weeks. Hydroxychloroquine treatment did not alter lupus disease activity (assessed by plasma double-stranded DNA autoantibodies) but prevented hypertension, cardiac and renal hypertrophy, proteinuria, and renal injury in lupus mice. Aortae from lupus mice showed reduced endothelium-dependent vasodilator responses to acetylcholine and enhanced contraction to phenylephrine, which were normalized by hydroxychloroquine or antioxidant treatments. No differences among all experimental groups were found in both the relaxant responses to acetylcholine and the contractile responses to phenylephrine in rings incubated with the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester. Vascular reactive oxygen species content and mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase subunits NOX-1 and p47(phox) were increased in lupus mice and reduced by hydroxychloroquine or antioxidants. Chronic hydroxychloroquine treatment reduced hypertension, endothelial dysfunction, and organ damage in severe lupus mice, despite the persistent elevation of anti-double-stranded DNA, suggesting the involvement of new additional mechanisms to improve cardiovascular complications.
Assuntos
Injúria Renal Aguda/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Hidroxicloroquina/uso terapêutico , Hipertensão/tratamento farmacológico , Rim/efeitos dos fármacos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Endotélio Vascular/fisiopatologia , Inibidores Enzimáticos/farmacologia , Feminino , Hidroxicloroquina/farmacologia , Hipertensão/complicações , Hipertensão/fisiopatologia , Rim/fisiopatologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/fisiopatologia , CamundongosRESUMO
The purpose was to analyse the cardiac and renal capillary density and glomerular morphology resulting from a chronic excess or deficiency of thyroid hormones (THs) in rats. We performed histopathological, morphometrical and immunohistochemical analyses in hypothyroid and hyperthyroid rats to evaluate the density of mesenteric, renal and cardiac vessels at 4 weeks after induction of thyroid disorders. The main angiogenic factors in plasma, heart and kidney were measured as possible mediators of vascular changes. Mesenteric vessel branching was augmented and decreased in hyper- and hypothyroid rats respectively. The numerical density of CD31-positive capillaries was higher in left and right ventricles and in cortical and medullary kidney from both hyper- and hypothyroid rats vs controls. Numbers of podocytes and glomeruli per square millimetre were similar among groups. Glomerular area and percentage mesangium were greater in the hyperthyroid vs control or hypothyroid groups. No morphological renal lesions were observed in any group. Vascularisation of the mesenteric bed is related to TH levels, but an increased capillarity was observed in heart and kidney in both thyroid disorders. This increase may be produced by higher tissue levels of angiogenic factors in hypothyroid rats, whereas haemodynamic factors would predominate in hyperthyroid rats. Our results also indicate that the renal dysfunctions of thyroid disorders are not related to cortical or medullary microvascular rarefaction and that the proteinuria of hyperthyroidism is not secondary to a podocyte deficit. Finally, TH or its analogues may be useful to increase capillarity in renal diseases associated with microvascular rarefaction.
Assuntos
Vasos Coronários/patologia , Hipertireoidismo/patologia , Hipotireoidismo/patologia , Glomérulos Renais/patologia , Rim/irrigação sanguínea , Microvasos/patologia , Animais , Vasos Coronários/metabolismo , Fator 2 de Crescimento de Fibroblastos/sangue , Fator 2 de Crescimento de Fibroblastos/metabolismo , Mesângio Glomerular/irrigação sanguínea , Mesângio Glomerular/metabolismo , Mesângio Glomerular/patologia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Hipertireoidismo/sangue , Hipertireoidismo/metabolismo , Hipertireoidismo/fisiopatologia , Hipotireoidismo/sangue , Hipotireoidismo/metabolismo , Hipotireoidismo/fisiopatologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Glomérulos Renais/irrigação sanguínea , Glomérulos Renais/metabolismo , Glomérulos Renais/fisiopatologia , Masculino , Microvasos/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Podócitos/metabolismo , Podócitos/patologia , Proteinúria/etiologia , Ratos , Ratos Wistar , Ribonuclease Pancreático/sangue , Ribonuclease Pancreático/metabolismo , Hormônios Tireóideos/sangue , Hormônios Tireóideos/metabolismo , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
El síndrome hemofagocítico es una condición clínica e histológica grave, secundaria a diferentes procesos. La glomerulonefritis colapsante es una podocitopatía proliferativa, generalmente de pronóstico desfavorable para la función renal. Se presenta un caso en el que las dos condiciones aparecieron asociadas, lo cual es una forma infrecuente de presentación del linfoma hepatoesplénico de células T. Se discute, asimismo, el papel de los marcadores de desdiferenciación podocitaria en esta glomerulopatía, y se revisan la fisiopatología y el tratamiento.
The hemophagocytic syndrome is a serious clinical-histological entity secondary to different diseases. Collapsing glomerulonephritis is a proliferative podocytopathy that usually has an unfavorable renal prognosis. We present a case in which both entities were associated, which is an infrequent form of hepatosplenic T-cell lymphoma. In addition, we review the role of the markers of podocyte dedifferentiation in this glomerulopathy and its pathophysiology and treatment.
Assuntos
Linfo-Histiocitose Hemofagocítica , Glomerulonefrite , Antígenos de Diferenciação , Insuficiência Renal , Linfoma , Transtornos LinfoproliferativosRESUMO
No disponible
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Humanos , Feminino , Adulto , Glomerulonefrite/fisiopatologia , Complexo Antígeno-Anticorpo , Mononucleose Infecciosa/complicações , Herpesvirus Humano 4/patogenicidadeRESUMO
BACKGROUND: Oral melanoacanthoma (OMA) is an uncommon, reactive, pigmented mucocutaneous lesion. It is a rapidly growing, well-circumscribed, small, brown-to-black, solitary or multifocal macule that is characterized histopathologically by proliferation of keratinocytes and pigment-laden dendritic melanocytes. CASE DESCRIPTION: At the end of a one-month healing period after dental implant surgery, a 63-year-old white woman had pigmented lesions at different oral mucosal sites (hard palate, buccal mucosa and left maxillary tuberosity) that showed macrophages exhibiting iron and melanin in multiple areas of the lamina propria. The authors obtained biopsy specimens from all the lesions for histologic and immunohistochemical analyses and light-microscopy study. CONCLUSIONS AND CLINICAL IMPLICATIONS: Surgery could have been causal or incidental to the appearance of these lesions. Clinicians should be aware of this possible event and make a correct and pathologically confirmed differential diagnosis.
Assuntos
Acantoma/diagnóstico , Implantes Dentários , Melanose/diagnóstico , Doenças da Boca/diagnóstico , Neoplasias Bucais/diagnóstico , Complicações Pós-Operatórias , Células Dendríticas/patologia , Implantação Dentária Endóssea , Diagnóstico Diferencial , Feminino , Neoplasias Gengivais/diagnóstico , Humanos , Ferro/análise , Macrófagos/patologia , Melaninas/análise , Melanócitos/patologia , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Palato Duro/patologiaRESUMO
AA (secondary) amyloidosis is one of the most severe and uncommon complications of several rheumatic disorders and chronic infections such as tuberculosis (TB). Successful treatment depends on the control of the underlying inflammatory process, what can lead to an improvement or a regression in organ dysfunction. If the disorder persists, it has been reported in some cases of AA amyloidosis secondary to rheumatic diseases, that the use of biologic therapy is so far the only opportunity to reduce the development of AA amyloidosis and to reverse established deposits. We report herein a case of a latent TB infection complicated by a life-threatening AA amyloidosis presented as nephrotic syndrome. After an adequate antituberculostatic treatment, AA amyloidosis remained active and Tocilizumab (TCZ) was started with a dramatic resolution of the proteinuria, stabilization of the amyloid deposits and improvement in general condition.