RESUMO
Purpose: The main purpose of this study was to report a case of cystoid macular edema (CME) after gonioscopy-assisted transluminal trabeculotomy (GATT). Methods: We describe the case of a 73-year-old woman with ocular hypertension and history of cataract surgery combined with posterior vitrectomy and epiretinal membrane peeling 2 years before, who developed CME after uncomplicated GATT procedure. Results: Uneventful GATT surgery was performed in an eye with ocular hypertension. A month after GATT surgery, the patient com-plained of blurry vision. Best corrected visual acuity had deteriorated from 20/20 on Snellen chart, to 20/70. The patient was diagnosed with CME. Treatment with topical non-steroidal anti-inflammatory drug (NSAID) and topical corticosteroids for one month, and oral carbonic anhydrase inhibitor for one week achieved a total CME regression with recovery of a normal macular and foveal architecture. Conclusions: Surgery-induced CME may occur following stand-alone microinvasive glaucoma surgery (MIGS) such as GATT. It would be worthwhile to conduct studies to explore whether the prophylactic use of NSAID and corticosteroids is justified.
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Glaucoma de Ângulo Aberto , Edema Macular , Hipertensão Ocular , Trabeculectomia , Corticosteroides/efeitos adversos , Idoso , Anti-Inflamatórios não Esteroides , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/cirurgia , Gonioscopia , Humanos , Pressão Intraocular , Edema Macular/etiologia , Estudos Retrospectivos , Trabeculectomia/efeitos adversos , Trabeculectomia/métodosRESUMO
Full-thickness macular hole is a rare complication of macular telangiectasia type 2, and its treatment is still controversial. A patient with a full-thickness macular hole secondary to macular telangiectasia type 2 underwent vitreoretinal surgery with a plasma rich in growth factors membrane in the macular hole. At the sixth month of follow-up, anatomical and functional improvements were achieved, with no adverse effects. Plasma rich in growth factors is a new option, with advantages due to its biological properties that achieves good results in terms of safety and effectiveness in the surgical treatment of macular hole.
Assuntos
Perfurações Retinianas , Telangiectasia Retiniana , Humanos , Perfurações Retinianas/etiologia , Perfurações Retinianas/cirurgia , Telangiectasia Retiniana/complicações , Telangiectasia Retiniana/terapia , Vitrectomia/métodosRESUMO
Resumen Objetivo: Mostrar los resultados en el corto y mediano plazo del tratamiento endovascular de angioplastia transluminal percutánea (ATP) con balón en pacientes en estado de isquemia crítica por enfermedad arterial obstructiva infrapoplítea. Materiales y Método: Estudio descriptivo, observacional, retrospectivo. Se incluyeron los pacientes hospitalizados entre 2009 y 2018 por isquemia crítica Fontaine III o IV sometidos a una ATP del territorio infrapoplíteo. Se observó como objetivos primarios la preservación de la extremidad afectada y la mortalidad posoperatoria a un año plazo, y como objetivos secundarios los procedimientos adicionales en pacientes con lesiones o necrosis distales, estadía hospitalaria, complicaciones posoperatorias y necesidad de reintervención. Resultados: Se incluyeron 42 pacientes con un promedio de edad de 66 años (46-82), con importantes comorbilidades. Un 83,3% ingresó en etapa Fontaine IV. En 16 casos se realizó una angioplastia percutánea en más de una arteria. No se colocó stents. Se presentaron complicaciones en 3 pacientes, 2 requirieron una amputación mayor y en otro se debió efectuar un nuevo procedimiento endovascular de rescate. La estadía hospitalaria promedio fue 22 días. No hubo mortalidad precoz posprocedimiento. La mortalidad global a un año fue 9,5%. A todos los pacientes en etapa Fontaine IV se les efectuó algún procedimiento adicional, a 31 una amputación menor, 3 cerraron sus lesiones por segunda intención y en otro se realizó un injerto dermo-epidérmico. De los 35 pacientes con seguimiento, 77% preservó su extremidad a un año. Conclusión: La reparación endovascular mediante una angioplastia percutánea en estos casos es un procedimiento seguro y tiene una alta tasa de preservación de la extremidad inicial a un año de seguimiento.
Aim: Show initial and midterms results of endovascular Percutaneous Transluminal Angioplasty (PTA) in critical limb isquemia (CLI) patients caused by below-the-knee arterial disease. Materials and Method: Observational, descriptive and retrospective study. 42 CLI patients admitted in our hospital from 2009 until 2018 with Fontaine III or IV treated by PTA in infrapopliteal arteries were analyzed, collecting demographic, clinical and surgical characteristics, additional procedures in Fontaine IV, hospital stay, postoperative complications, need of reintervention, limb preservation and mortality with one year follow-up after procedure. Results: 42 patients, average age 66 year-old (46-82), with significant comorbidities. Fontaine IV stage patients were 83.3%. In 16 cases more than one artery was intervened. No stent revascularization was performed. Complications occurred in 3 patients, 2 required major amputation and an urgent endovascular reintervention was required in another. Average hospital stay was 22 days with no post-operative mortality. One-year global mortality was 9.5 One-year follow-up in 35 patients shows that 77% preserved their limb. Conclusión: Percutaneous transluminal angioplasty procedure in this patients has a high rate of limb preservation in a one-year follow-up. There was no post-operative mortality.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/terapia , Angioplastia com Balão/métodos , Isquemia/cirurgia , Resultado do Tratamento , Angioplastia com Balão/efeitos adversos , Isquemia/epidemiologiaRESUMO
Full-thickness macular hole is a rare complication of macular telangiectasia type 2, and its treatment is still controversial. A patient with a full-thickness macular hole secondary to macular telangiectasia type 2 underwent vitreoretinal surgery with a plasma rich in growth factors membrane in the macular hole. At the sixth month of follow-up, anatomical and functional improvements were achieved, with no adverse effects. Plasma rich in growth factors is a new option, with advantages due to its biological properties that achieves good results in terms of safety and effectiveness in the surgical treatment of macular hole.
RESUMO
Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2-9% of all cancer patients, mostly 60-75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.
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Oncologia/normas , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/terapia , Patologia Clínica/normas , Idoso , Consenso , Humanos , Oncologia/organização & administração , Pessoa de Meia-Idade , Patologia Clínica/organização & administração , Sociedades Médicas/organização & administração , Sociedades Médicas/normas , EspanhaRESUMO
Introducción: Más de la tercera parte de los homicidios reportados a nivel mundial tienen lugar en el continente Americano, siendo Chile uno de los países con las tasas más bajas de Latinoamérica. Actualmente, son escasos los estudios que caracterizan el acto homicida en nuestro país. Se caracterizó el acto homicida según las autopsias realizadas por el Servicio Médico Legal (SML) de Concepción, durante el periodo 2011-2015. Materiales y método: Se realizó un estudio transversal de informes de autopsia con causa homicidio durante los años 2011 a 2015, realizadas por el SML de Concepción, utilizándose las variables: género, edad, procedencia, lugar de ocurrencia del homicidio, estado civil, ocupación, patologías asociadas, causa de muerte, tipo de arma utilizada, alcoholemia, examen toxicológico y atención en centro asistencial. El estudio fue aprobado por comité de ética. Resultados: Del total de autopsias en el periodo 2011-2015; 5.92% (241) correspondieron a homicidios, de los cuales un 89.6% fueron víctimas de sexo masculino. Del total de homicidios estudiados la edad promedio fue de 33 años, un 58.3% del total ocurrieron en vía pública y 42.1% fallecieron por trauma torácico complicado. Finalmente del total de homicidios, un 49,2% poseían alcoholemia negativa y 49.2% examen toxicológico negativo. Discusión: En Chile, el homicidio afecta a una pequeña porción de la población, acercándose a las bajas tasas que presentan diversos países de Europa. En su mayoría, los homicidios reportados fueron hombres entre los 18 y 29 años de edad, resultado similar a lo descrito a nivel mundial.
Introduction: More than a third part of the worldwide reported homicides takes place in the whole american continent, and Chile is one the countries with the lowest rates in latin america. Only a few are the studies that characterize the homicidal act in our country. Characterize the homicide act according to the autopsies reports performed by the Legal Medical Service (SML) of Concepción, during the period 2011-2015. Materials and methods: We made a transversal study with the autopsies reports classified as homicide, performed by the SML Concepción, between the years 2011 and 2015 using variables such as: gender, age, place of residence, place of homicidal act, marital state, occupation, comorbidities, death cause, weapon, blood alcohol concentration, toxicological results and medical assistance. An ethic committee approved the study. Results: From the total autopsies between 2011 and 2015; 5.92% (241) were homicides, of which 89.4% were men. The average age of homicides victims was 33 years old, 58.3% occurred on public areas and 42.1% were died because a complicated thoracic traumatism. And finally from the total homicides, 49.2% had none alcohol in blood such as the 49.2% as well had negative toxicological test. Discussion: In Chile, homicide affects a few number of its population, approaching the low rates that some european countries have. The most of the homicides reported were men between 18 to 29 years old, similar results comparing with the worldwide statistics.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Autopsia/estatística & dados numéricos , Medicina Legal/estatística & dados numéricos , Homicídio/estatística & dados numéricos , Chile/epidemiologia , Estudos Transversais , Causas de Morte , Distribuição por Idade e SexoRESUMO
This study was performed to determine the effects of gamma irradiation on UV spectrum on maca, total content of polyphenols, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activities and in vivo biological activities of red and black maca extracts (Lepidium meyenii). Adult mice of the strain Swiss aged 3 months and weighing 30-35 g in average were used to determine biological activities. Daily sperm production, effect on testosterone-induced prostate hyperplasia and forced swimming test were used to determine the effect of irradiation on biological activities of maca extracts. Irradiation did not show differences in UV spectrum but improves the amount of total polyphenols in red maca as well as in black maca extracts. In both cases, black maca extract has more content of polyphenols than red maca extract (p < 0.01). Gamma irradiation significantly increased the antioxidant capacity (p < 0.05). No difference was observed in daily sperm production when irradiated and nonirradiated maca extract were administered to mice (p > 0.05). Black maca extract but not red maca extract has more swimming endurance capacity in the forced swimming test. Irradiation of black maca extract increased the swimming time to exhaustion (p < 0.05). This is not observed with red maca extract (p > 0.05). Testosterone enanthate (TE) increased significantly the ventral prostate weight. Administration of red maca extract in animals treated with TE prevented the increase in prostate weight. Irradiation did not modify effect of red maca extract on prostate weight (p > 0.05). In conclusion, irradiation does not alter the biological activities of both black maca and red maca extracts. It prevents the presence of microorganisms in the extracts of black or red maca, but the biological activities were maintained.
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Antioxidantes/farmacologia , Lepidium/química , Fenóis/química , Extratos Vegetais/farmacologia , Animais , Antioxidantes/química , Feminino , Raios gama , Masculino , Camundongos , Extratos Vegetais/química , Espectrofotometria Atômica , Raios UltravioletaRESUMO
In 2011, the Spanish Society of Medical Oncology and the Spanish Society of Pathology started a joint project to establish recommendations on biomarker testing in patients with advanced non-small-cell lung cancer based on the current evidence. Most of these recommendations are still valid, but new evidence requires some aspects to be updated. Specifically, the recommendation about which biomarkers to test in which patients is being amended, and the best way to manage tumour samples and minimum requirements for biomarker test material are defined. Suitable techniques for testing for epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement are also reviewed, and a consensus is reached on which situations warrant re-biopsy.
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Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Consenso , Gerenciamento Clínico , Humanos , Neoplasias Pulmonares/metabolismo , Oncologia , Sociedades Médicas , EspanhaRESUMO
OBJECTIVE: Breast cancer is a heterogeneous neoplasm. Distinct subtypes of breast cancer have been defined, suggesting the existence of molecular differences contributing to their clinical outcomes. However, the molecular differences between human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative breast cancer tumors remain unclear. The aim of this study was to identify a gene expression profile for breast tumors based on their HER2 status. METHODS: The HER2 status was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 54 breast tumor samples. Using Affymetrix microarray data from these breast tumors, we established the expression profiling of breast cancer based on HER2 IHC and FISH results. To validate microarray experiment data, real-time quantitative reverse transcription-PCR was performed. RESULTS: We found significant differences between the HER2-positive and HER2-negative breast tumor samples, which included overexpression of HER2, other genes located on 17q12 and genes functionally related to migration. CONCLUSION: Our study shows the potential of integrated genomic profiling to shed light on the molecular knowledge of HER2-positive breast tumors.
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Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica/genética , Receptor ErbB-2/genética , Transcriptoma , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/genética , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Análise por Conglomerados , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Neoplásico/genética , Receptor ErbB-2/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Current breast cancer research involves the study of many different prognosis factors: primary tumor size, lymph node status, tumor grade, tumor receptor status, p53, and ki67 levels, among others. High-throughput microarray technologies are allowing to better understand and identify prognostic factors in breast cancer. But the massive amounts of data derived from these technologies require the use of efficient computational techniques to unveil new and relevant biomedical knowledge. Furthermore, integrative tools are needed that effectively combine heterogeneous types of biomedical data, such as prognosis factors and expression data. The objective of this study was to integrate information from the main prognostic factors in breast cancer with whole-genome microarray data to identify potential associations among them. We propose the application of a data mining approach, called fuzzy association rule mining, to automatically unveil these associations. This paper describes the proposed methodology and illustrates how it can be applied to different breast cancer datasets. The obtained results support known associations involving the number of copies of chromosome-17, HER2 amplification, or the expression level of estrogen and progesterone receptors in breast cancer patients. They also confirm the correspondence between the HER2 status predicted by different testing methodologies (immunohistochemistry and fluorescence in situ hybridization). In addition, other interesting rules involving CDC6, SOX11, and EFEMP1 genes are identified, although further detailed studies are needed to statistically confirm these findings. As part of this study, a web platform implementing the fuzzy association rule mining approach has been made freely available at: http://www.genome2.ugr.es/biofar .
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Diagnóstico por Computador/métodos , Lógica Fuzzy , Proteínas de Neoplasias/análise , Reconhecimento Automatizado de Padrão/métodos , Algoritmos , Feminino , Humanos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: The Her2/neu status is of great clinical value in breast tumor patients. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) techniques are the test of choice for many practicing pathologies. The main objective of this retrospective study was to investigate the relationship between Her2/neu breast cancer amplification and overexpression (DNA, mRNA and protein). METHODS: To accomplish this goal, we evaluated Her2/neu mRNA expression by real-time quantitative RT-PCR, gene amplification by FISH and protein expression by IHC. RESULTS: An excellent correlation between FISH and IHC Her2/neu results was observed, confirming that protein levels were directly related to DNA amplification. Polysomy 17 was frequently found in tumors showing Her2/neu overexpression. However, we did not find any statistically significant correlation among DNA, mRNA and protein levels, suggesting that Her2/neu could be post-transcriptionally regulated. CONCLUSIONS: There was a highagreement between Her2/neu gene amplification and protein overexpression but not mRNA expression levels. Nevertheless, IHC3+ and FISH-positive tumors indicated higher expression levels of Her2/neu mRNA by RT-PCR than those observed in IHC and FISH-negative tumors. These findings question the relevance of quantitative RT-PCR in routine assessment of Her2/neu overexpression in human breast cancer in the clinical laboratory setting.
Assuntos
Neoplasias da Mama/genética , Genes erbB-2 , Receptor ErbB-2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente/métodos , RNA Mensageiro/análise , Receptor ErbB-2/metabolismo , Estudos RetrospectivosRESUMO
A total of 93 frozen primary renal cell carcinoma (RCC) samples and 31 frozen samples of corresponding normal renal tissue were analyzed for human leukocyte antigen (HLA) class I and HLA-DR expression. Unexpectedly, HLA class I expression was much higher on RCC cells than on normal renal tubular cells. Immunohistochemistry analysis of frozen and paraffin-embedded tissue samples, applying an extended panel of specific anti-HLA monoclonal antibodies, showed elevated HLA class I antigen expression in 95.6% of the tumors vs only 12.9% of normal renal tissues. These findings were confirmed by molecular analysis of HLA heavy chain and beta2-microglobulin (beta2m) transcription levels using quantitative real-time polymerase chain reaction (PCR) on microdissected tissue samples (isolated tumor nests and autologous normal renal tubules) from four patients. These results might help to explain the relatively high success rate of immunotherapy in patients with RCC. The molecular mechanism underlying the increased HLA class I expression in RCC has yet to be elucidated.
Assuntos
Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Antígenos HLA-DR/genética , Antígenos de Histocompatibilidade Classe I/análise , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Carcinoma de Células Renais/genética , Antígenos HLA-DR/biossíntese , Antígenos HLA-DR/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Imuno-Histoquímica , Rim/química , Rim/imunologia , Neoplasias Renais/genética , Leucócitos/química , Leucócitos/imunologia , Leucócitos/patologia , Inclusão em ParafinaRESUMO
BACKGROUND AND PURPOSE: Escherichia coli Nissle 1917 is a probiotic strain used in the treatment of intestinal immune diseases, including ulcerative colitis. The aim of the present study was to test if this probiotic bacterium can also show systemic immunomodulatory properties after oral administration. EXPERIMENTAL APPROACH: The probiotic strain was administered to rats or mice for 2 weeks before its assay in two experimental models of altered immune response, the trinitrobenzenesulphonic acid (TNBS) model of rat colitis, localized in the colon, and the lipopolysaccharide (LPS) model of systemic septic shock in mice. Inflammatory status was evaluated both macroscopically and biochemically after 1 week in the TNBS model or after 24 h in the LPS shock model. In addition, splenocytes were obtained from mice and stimulated, ex vivo, with concanavalin A or LPS to activate T or B cells, respectively, and cytokine production (IL-2, IL-5 and IL-10) by T cells and IgG secretion by B cells measured. KEY RESULTS: E. coli Nissle 1917 was anti-inflammatory in both models of altered immune response. This included a reduction in the pro-inflammatory cytokine tumour necrosis factor-alpha both in the intestine from colitic rats, and in plasma and lungs in mice treated with LPS. The systemic beneficial effect was associated with inhibited production of the T cell cytokines and by down-regulation of IgG release from splenocyte-derived B cells. CONCLUSIONS AND IMPLICATIONS: The anti-inflammatory effects of E. coli Nissle 1917 given orally were not restricted to the gastrointestinal tract.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Escherichia coli , Mediadores da Inflamação/antagonistas & inibidores , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/toxicidade , Probióticos/administração & dosagem , Choque Séptico/patologia , Choque Séptico/prevenção & controle , Administração Oral , Animais , Células Cultivadas , Feminino , Mediadores da Inflamação/administração & dosagem , Mediadores da Inflamação/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Wistar , Choque Séptico/induzido quimicamenteRESUMO
BACKGROUND: Gene therapy is a new method used to induce cancer cell differentiation. Our group previously showed that transfection of the gef gene from Escherichia coli, related to cell-killing functions, may be a novel candidate for cancer gene therapy. Its expression leads to cell cycle arrest unrelated to the triggering of apoptosis in MS-36 melanoma cells. OBJECTIVES: To determine the basis of the antiproliferative effect of the gef gene in this cell line. METHODS: Transmission electron microscopy, apoptosis analysis by confocal microscopy, flow cytometry and immunocytochemical analysis were used. RESULTS: Ultrastructural analysis showed a strikingly different morphology after treatment with dexamethasone and expression of the gef gene, with large accumulations of pigment throughout the cell cytoplasm and presence of melanosomes in different stages of development. High mitochondrial turnover and myeloid bodies, characteristics of neurone cells, were also observed. In addition, both immunocytochemical and indirect immunofluorescence analysis demonstrated a significant decrease in HMB-45, Ki-67 and CD44 antigen expression and an increase in S100 and p53 expression in gef gene-transfected MS-36 melanoma cells that were correlated with the duration of dexamethasone treatment. In the present work, we report that gef gene not only reduces cell proliferation in transfected melanoma MS-36TG cell line but also induces morphological changes clearly indicative of melanoma cell differentiation and a reduction in tumour malignancy. CONCLUSIONS: These findings support the hypothesis that the gef gene offers a new approach to differentiation therapy in melanoma.
Assuntos
Proteínas de Ligação a DNA/genética , Melanoma/genética , Neoplasias Cutâneas/genética , Fatores de Transcrição/genética , Apoptose , Diferenciação Celular/genética , Proliferação de Células , Dexametasona/farmacologia , Humanos , Receptores de Hialuronatos/metabolismo , Melanoma/patologia , Melanoma/ultraestrutura , Microscopia Confocal , Microscopia Eletrônica , Proteínas de Neoplasias/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/ultraestrutura , Transfecção , Células Tumorais CultivadasRESUMO
Although human mucosal leishmaniasis is much more common in Latin America, a few cases that are the result of local transmission occur in Europe. A suspected case of leishmaniasis is usually confirmed by the demonstration of amastigotes in smears, the culture of promastigotes from blood or tissue samples, or the PCR-based demonstration of leishmanial DNA. Biopsies may contain too few parasites to be found positive by microscopy or culture, however, and then a diagnosis may be difficult, especially in regions where human leishmaniasis in general or particular forms of the disease are rarely seen. The aim of the present study was to investigate the histopathological characteristics of three Spanish cases of non-granulomatous mucosal leishmaniasis caused by Leishmania infantum. The hope was that the information collected will help European clinicians diagnose such cases, even when amastigotes cannot be readily demonstrated.
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Leishmania infantum/isolamento & purificação , Leishmaniose Mucocutânea/patologia , Adulto , Animais , Antiprotozoários/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Leishmaniose Mucocutânea/tratamento farmacológico , Leishmaniose Mucocutânea/parasitologia , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologia , Resultado do TratamentoRESUMO
Testosterone is essential for the growth and function of the luminal prostate cells, but it is also critical for the development of prostate cancer, which in the majority of the cases derives from luminal cells. Cytochrome P450 3A (CYP3A) enzymes hydroxylate testosterone and dehydroepiandrosterone to less active metabolites, which might be the basis for the association between CYP3A polymorphisms and prostate cancer. However, it is unknown whether the CYP3A enzymes are expressed at relevant levels in the prostate and which polymorphisms could affect this tissue-specific CYP3A activity. Thus, we measured CYP3A4, CYP3A5, CYP3A7, and CYP3A43 mRNA in 14 benign prostatic hyperplasias and ten matched non-tumoral/tumoral prostate samples. We found that CYP3A5 mRNA in non-tumoral prostate tissue was 10% of the average amount of liver samples, whereas the expression of the other CYP3A genes was much lower. Similarly to liver, CYP3A5*3 polymorphism decreased CYP3A5 mRNA content 13-fold. CYP3A5 protein was detected in non-tumoral prostate microsomes by western blot, and immunohistochemistry (IHC) localized CYP3A5 exclusively in the basolateral prostate cells. In contrast to the normal tissue, IHC and RT-PCR showed that tumoral tissue lacked CYP3A5 expression. In conclusion, prostate basolateral cells express high levels of CYP3A5 which dramatically decrease in tumoral tissue. This finding supports an endogenous function of CYP3A5 related to the metabolism of intra-prostatic androgens and cell growth, and that polymorphisms affecting CYP3A5 activity may result in altered prostate cancer risk and aggressiveness.
Assuntos
Carcinoma/genética , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Próstata/metabolismo , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma/metabolismo , Carcinoma/patologia , Citocromo P-450 CYP3A , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo Genético , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologiaRESUMO
OBJECTIVE: To determine the prevalence of alpha-synuclein (AS) aggregates in abdominopelvic autonomic plexuses in the general population and to evaluate the relationship between this finding and the subsequent development of neurologic dysfunction. METHODS: First, surgical specimens from 100 patients (ages 44 to 84) undergoing a wide resection of an abdominopelvic organ were examined by anti-AS immunostaining. Second, 16 patients (6 AS+ and 10 randomly selected AS-) participated in yearly double-blinded neurologic assessments. RESULTS: AS aggregates were found in autonomic plexuses in 9% of the whole sample (95% CI 3.4 to 14.6%) but were more common in vesicoprostatic (26%) than in digestive tract (4%) specimens. At 16 months after the biopsy, no prevalent cases of Parkinson disease, dementia, or autonomic failure were diagnosed among participants. One AS+ patient had previously been diagnosed with REM sleep behavior disorder. Seven of 10 control subjects but none of the 6 AS+ patients had a diagnosis of hypertension (p = 0.01). During phase IV of Valsalva maneuver, AS+ group exhibited a longer blood pressure recovery time (p = 0.03), with one patient showing absence of blood pressure overshoot. Cardiac [(123)I]metaiodobenzylguanidine uptake was reduced in the AS+ group (p = 0.03). Striatal [(123)I]ioflupane uptake was abnormally low in only one AS+ patient. At 30 months after the biopsy, lower cardiac and striatal uptake values tended to correlate with higher Unified Parkinson's Disease Rating Scale III scores (p = 0.07). CONCLUSION: The common presence of alpha-synuclein aggregates in peripheral autonomic neurons may represent an early presymptomatic phase in the development of Lewy body disorders.
Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Gânglios Autônomos/metabolismo , Doença por Corpos de Lewy/fisiopatologia , Doença de Parkinson/fisiopatologia , alfa-Sinucleína/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças do Sistema Nervoso Autônomo/epidemiologia , Doenças do Sistema Nervoso Autônomo/patologia , Biomarcadores/análise , Biomarcadores/metabolismo , Sistema Cardiovascular/inervação , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Estudos de Coortes , Comorbidade , Corpo Estriado/metabolismo , Corpo Estriado/fisiopatologia , Estudos Transversais , Progressão da Doença , Feminino , Gânglios Autônomos/patologia , Gânglios Autônomos/fisiopatologia , Humanos , Imuno-Histoquímica , Corpos de Lewy/metabolismo , Corpos de Lewy/patologia , Doença por Corpos de Lewy/epidemiologia , Doença por Corpos de Lewy/patologia , Substâncias Macromoleculares/metabolismo , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Neurônios/metabolismo , Neurônios/patologia , Doença de Parkinson/epidemiologia , Doença de Parkinson/patologia , Valor Preditivo dos Testes , PrevalênciaRESUMO
Human embryonic stem cells (hESCs) represent a promise for future strategies of tissue replacement. However, there are different issues that should be resolved before these cells can be used in cellular therapies; among others, the rejection of transplantable hESCs as a result of HLA incompatibility between donor cells and recipients. The hESCs exhibit a weak HLA class I expression on the cell surface, but today the responsible mechanisms are unknown. We have analyzed the level expression of HLA class I heavy chain, beta2-microglobulin (beta2-m), and antigen-processing machinery (APM) components (TAP1, TAP2, LMP2, LMP7, and Tapasin) using the HS293 hESC line by real-time quantitative RT-PCR. This analysis has revealed a low expression of beta2-m, HLA-B, and Tapasin, and an absence of expression of: TAP1, TAP2, LMP2, and LMP7 genes in the HS293 hESC line respect to the embryoid bodies (EBs) and the induced stem cells with IFNgamma (with significant differences, p<0.05). The lack or loss of HLA class I molecules due to the down-regulation of the APM components has been frequently found in tumors of different histology as specific mechanisms of immune-evasion. We described for the first time in this report that the hESCs shared similar mechanisms with respect to tumor cells responsible for the weak HLA class I expression on the cell surface.
Assuntos
Células-Tronco Embrionárias/metabolismo , Regulação da Expressão Gênica , Antígenos de Histocompatibilidade Classe I/metabolismo , Biomarcadores/metabolismo , Células-Tronco Embrionárias/citologia , Imunofluorescência , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Human embryonic stem alls (hESC) have an unlimited capacity of proliferation and self-renewal resulting in a promise for future applications in regenerative medicine. One major problem derived from their use in cellular therapy protocols is the immunological rejection due to HLA incompatibility. Currently, there are four strategies to prevent allograft rejection of hESC; the development of a ''universal hESC line'' with lack of HLA class 1 expression; the creation of nuclear transfer hESC line; the development of hESC line banks; and the generation of haemopoietic chimerism.