RESUMO
Cisplatin is one of the most potent chemotherapeutic antitumor drugs used in the treatment of a wide range of solid tumors. Its primary dose-limiting side effect is nephrotoxicity. The organic anion transporter 5 (Oat5) is exclusively localized in the kidney. Oat5 urinary excretion was recently proposed as a potential early biomarker of acute kidney injury (AKI). The aim of this study was to evaluate Oat5 renal expression and its urinary excretion in rats exposed to different doses of cisplatin, in comparison with traditional markers of renal injury, like renal histology, creatinine and urea plasma levels, creatinine clearance, protein and glucose urinary levels and urinary alkaline phosphatase (AP) activity. Male Wistar rats were treated with a single injection of cisplatin at different doses of 1, 2, 5 and 10 mg/kg b.w., i.p. (Cis1, Cis2, Cis5 and Cis10, n = 4, respectively) and experiments were carried out 48 h after cisplatin administration. The renal expression of Oat5 was evaluated by immunohistochemistry and Western blotting. Oat5 abundance, AP activity, creatinine, glucose and proteins were assayed in urine. Creatinine clearance and creatinine and urea plasma levels were also evaluated. In this experimental model, plasma urea and creatinine levels, creatinine clearance, AP urinary activity and protein and glucose urinary levels were significantly modified only at the highest cisplatin dose of 10 mg/kg b.w., i.p., as compared to control rats. In contrast, Oat5 urinary abundance was increased in a dose-related manner after the administration of cisplatin. Oat5 urinary abundance was elevated at a dose as low as 1 mg/kg b.w., i.p., implying renal perturbation, when no modifications of traditional markers of renal injury are yet observed. Oat5 renal expression was decreased in a dose-related manner, both in homogenates and apical membranes from cisplatin-treated kidneys. The increase in urinary Oat5 excretion might explain the decrease in the amount of Oat5 molecules in the renal tubule cells. Hence, the preclinical animal results showed in this work propose that Oat5 urinary excretion might potentially serve as a non-invasive early biomarker of cisplatin-induced AKI.
Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Transportadores de Ácidos Dicarboxílicos/biossíntese , Nefropatias/induzido quimicamente , Nefropatias/urina , Rim/metabolismo , Animais , Biomarcadores/urina , Western Blotting , Creatinina/sangue , Transportadores de Ácidos Dicarboxílicos/urina , Eletroforese , Glicosúria/induzido quimicamente , Imuno-Histoquímica , Rim/patologia , Córtex Renal/patologia , Nefropatias/patologia , Testes de Função Renal , Túbulos Renais/patologia , Masculino , Membranas/metabolismo , Membranas/patologia , Proteinúria/induzido quimicamente , Ratos , Ureia/sangueRESUMO
BACKGROUND: Low plasma triiodothyronine (T(3)) levels are considered a prognostic predictor of death in heart failure (HF) patients. AIM: To study an association between plasma T(3) levels and several cardiac, neurohormonal, and metabolic markers of HF. METHODS: A total of 133 ambulatory HF patients (114 males; mean age 63.2 years) with left ventricular ejection fraction <40% were enrolled. TSH, total tetraiodothyronine (T(4)) and T(3), N-terminal pro-brain natriuretic peptide (NT-proBNP), and other cardiac and metabolic parameters were measured. The lowest tertile of T(3) (group 1) was compared against the two upper ones (group 2). RESULTS: In simple logistic regression, the lowest T(3) tertile was associated with more advanced HF disease status: older (age: odds ratio (OR)=1.05; confidence interval (CI) 95% 1.01-1.09, P=0.004), lower functional capacity (walking test: OR=0.996; CI 95% 0.993-0.999, P=0.008), higher NT-proBNP (OR=1.64; CI 95% 1.19-2.27, P=0.003) and adiponectin levels (OR=1.07; CI 95% 1.02-1.11, P=0.004), lower DHEAS log-transformed (OR=0.50; CI 95% 0.31-0.80, P=0.004), and the presence of lower phase angle values as measured by body bioelectrical impedance analysis (OR=3.18; CI 95% 1.50-6.71, P=0.04) and worse renal function (OR=0.96; CI 95% 0.94-0.98, P=0.003). T(3) levels in the lowest tertile were independently associated with low phase angle values (OR=2.95, CI 95% 1.16-7.50, P=0.02) and the log transformation of DHEAS (OR=0.56; CI 95% 0.32-0.97, P=0.04). CONCLUSION: We have demonstrated an association between plasma T(3) levels in the lower range and other deranged hormonal and metabolic parameters in HF patients.
Assuntos
Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Tri-Iodotironina/deficiência , Idoso , Biomarcadores , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/patologia , Ecocardiografia , Impedância Elétrica , Teste de Esforço , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Hemodinâmica/fisiologia , Hormônios/sangue , Humanos , Inflamação/sangue , Modelos Logísticos , Masculino , Membranas/patologia , Pessoa de Meia-Idade , Neurotransmissores/sangue , Prognóstico , Estudos Prospectivos , Volume Sistólico/fisiologia , Tri-Iodotironina/sangue , Função Ventricular Esquerda/fisiologia , Caminhada/fisiologiaRESUMO
PURPOSE: to present a series of cases of membranous dysmenorrhea. METHODS: all the patients selected were under diagnostic suspicion, after being clinically attended in a private medical office due to the report of painful dysmenorrhea associated with spontaneous elimination of elastic material with uterine shape. Only relevant facts about the pain condition have been described, together with the present and previous medical history and life habits. The material eliminated was forwarded to the pathology laboratory, where the macro and microscopic analyses were done. Cases with no confirmation of membranous material elimination were not selected. After the diagnostic confirmation, literature up to 2008 was carried out using the MeSH method, with the words 'membranous dysmenorrheal'. RESULTS: three cases of dysmenorrhea were transcribed. Besides the characteristic picture of pain and vaginal elimination of elastic material, all the cases were associated with the use of hormonal contraceptive methods. CONCLUSIONS: despite the fact that there are only sporadic reports of cases of membranous dysmenorrhea in the scientific literature, this etiology must be considered in cases of pain associated with vaginal bleeding plus elimination of elastic or solid material. The final diagnosis depends on anatomopathological exam, which should not be dismissed. We highlight the need for more discussion about this pathology, to keep the professionals updated with the aim of exerting adequate diagnosis and therapeutics.
Assuntos
Dismenorreia/patologia , Adulto , Dismenorreia/classificação , Feminino , Humanos , Membranas/patologiaRESUMO
OBJETIVO: apresentar uma série de casos de dismenorreia membranosa. MÉTODOS: todas as pacientes foram selecionadas a partir da suspeição diagnóstica, após atendimento clínico em consultório privado por relato de dismenorreia dolorosa associada à eliminação espontânea de material elástico com formato semelhante a útero. Apenas fatos relevantes foram descritos do quadro álgico, história médica atual e pregressa e hábitos de vida. O material eliminado foi encaminhado para laboratório de patologia no qual ocorreu a análise macro e microscópica. Os casos em que não se pode provar a eliminação de material com característica membranácea não foram selecionados. Após a confirmação diagnóstica, realizou-se uma revisão da literatura até o ano de 2008 utilizando o método MeSH com o termo "membranous dysmenorrhea". RESULTADOS: três casos clínicos de dismenorreia foram transcritos. Todos os casos, além do quadro característico de dor e eliminação vaginal de material elástico, foram associados ao uso de métodos anticoncepcionais hormonais. CONCLUSÕES: embora haja apenas escassos relatos de caso de dismenorreia membranosa na literatura científica, sua etiologia deve ser suspeita em casos de dor associada a sangramento vaginal com eliminação de material elástico ou firme. O diagnóstico final é dependente do exame anatomopatológico que nunca deve ser dispensado. Observamos necessidade de mais discussões sobre esta patologia com o objetivo de manter o profissional atualizado para exercer diagnóstico e terapêutica adequados.
PURPOSE: to present a series of cases of membranous dysmenorrhea. METHODS: all the patients selected were under diagnostic suspicion, after being clinically attended in a private medical office due to the report of painful dysmenorrhea associated with spontaneous elimination of elastic material with uterine shape. Only relevant facts about the pain condition have been described, together with the present and previous medical history and life habits. The material eliminated was forwarded to the pathology laboratory, where the macro and microscopic analyses were done. Cases with no confirmation of membranous material elimination were not selected. After the diagnostic confirmation, literature up to 2008 was carried out using the MeSH method, with the words "membranous dysmenorrheal". RESULTS: three cases of dysmenorrhea were transcribed. Besides the characteristic picture of pain and vaginal elimination of elastic material, all the cases were associated with the use of hormonal contraceptive methods. CONCLUSIONS: despite the fact that there are only sporadic reports of cases of membranous dysmenorrhea in the scientific literature, this etiology must be considered in cases of pain associated with vaginal bleeding plus elimination of elastic or solid material. The final diagnosis depends on anatomopathological exam, which should not be dismissed. We highlight the need for more discussion about this pathology, to keep the professionals updated with the aim of exerting adequate diagnosis and therapeutics.
Assuntos
Adulto , Feminino , Humanos , Dismenorreia/patologia , Dismenorreia/classificação , Membranas/patologiaRESUMO
INTRODUCTION: Acute episodes of asthma are one of the most common respiratory emergencies, and status asthmaticus is the most severe respiratory impairment. Because "not all the wheezes are manifestations of asthma", the clinician needs to consider non asthmatic causes of wheezing in the differential diagnosis such as tracheal stenosis. CLINICAL CASE: 7 years old male, hispanic, non atopic background, with two previous cases of acute asthma. Current condition: 15 days of cough, dyspnea and wheezes, without fever. The physical examination revealed nasal flutter, use of accessory muscles of respiration, fatigue and bibasal hypoventilation. Mitomycin was applied during nasolaryngoscopy. He was discharged 17 days after with tracheal stenosis diagnosis. Biopsy reported respiratory epithelium with chronic inflammation and fibrosis. Six dilatations were performed because of persistent stenosis and he is being evaluated by infectologist and hematologist for repeated upper airway infections associated with cyclic neutropenia.
Assuntos
Erros de Diagnóstico , Neutropenia/complicações , Sons Respiratórios/etiologia , Estado Asmático/diagnóstico , Estenose Traqueal/diagnóstico , Doença Aguda , Biópsia , Espasmo Brônquico/diagnóstico , Espasmo Brônquico/etiologia , Criança , Diagnóstico Diferencial , Dilatação , Genes Dominantes , Gengivite/complicações , Humanos , Contagem de Leucócitos , Masculino , Membranas/patologia , Neutropenia/diagnóstico , Neutropenia/genética , Periodicidade , Exame Físico , Radiografia , Recidiva , Infecções Respiratórias/etiologia , Perda de Dente/complicações , Estenose Traqueal/diagnóstico por imagem , Estenose Traqueal/etiologia , Estenose Traqueal/patologia , Estenose Traqueal/terapiaRESUMO
Biochemical and histologic analyses were performed on interface membranes obtained at revision of aseptically loosened hip implants (n = 36) and knee implants (n = 16). Clinical failure occurred sooner in patients with uncemented total hip implants (Group 1) than in patients with cemented implants (Group 2) (p < 0.02). There was no difference in time to revision between the patients with uncemented implants (Group 3) and patients with cemented total knee implants (Group 4). Histologically, more small (< 5 mu) polyethylene particles were found within macrophages and fibroblasts in membranes from Groups 1 and 2. Polyethylene particles from failed total knees (> 10-100 mu) were larger than those from failed total hips. Large polyethylene fragments and foreign-body giant cells were more common in failed knees than failed total hip membranes. Biochemically, proteinase and cytokine activity in the tissue culture supernatant from all groups was higher than in the control tissue (p < 0.01). The activities of stromelysin, prostaglandin E2, interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor-alpha were higher in Groups 1 and 2 than in Groups 3 and 4 (p < 0.05). These findings support the hypothesis that interface membranes enveloping femoral (hip) and tibial (knee) components of failed total joint implants may promote bone resorption and aseptic loosening. The reason for slower failure of knee implants as compared with hip prostheses may be the lower level of biochemical activity and macrophage density that correlates closely with larger polyethylene particles.
Assuntos
Cimentos Ósseos , Cabeça do Fêmur/metabolismo , Cabeça do Fêmur/patologia , Prótese de Quadril , Prótese do Joelho , Falha de Prótese , Tíbia/metabolismo , Tíbia/patologia , Idoso , Citocinas/metabolismo , Endopeptidases/metabolismo , Feminino , Cabeça do Fêmur/diagnóstico por imagem , Humanos , Macrófagos/patologia , Masculino , Membranas/metabolismo , Membranas/patologia , Pessoa de Meia-Idade , Polietilenos/efeitos adversos , Polietilenos/uso terapêutico , Prostaglandinas E/metabolismo , Radiografia , Tíbia/diagnóstico por imagemRESUMO
Os autores apresentam uma análise de seus casos de "pucker" macular, correlacionando a AV com o estágio da doença. 2 casos säo mostrados, evidenciando alguns dos mecanismos propostos para esta alteraçäo da interface vítreo-retiniana
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Degeneração Macular/etiologia , Membranas/patologia , Retina/patologiaRESUMO
Forty-one patients with a unilateral, macular epiretinal membrane (ERM) underwent pars plana vitrectomy and membrane peeling to improve the visual acuity. The authors retrospectively reviewed the histopathology of the vitrectomy specimen in each instance to determine whether the presence of internal-limiting membrane (ILM) had an adverse effect on visual acuity. Eleven specimens contained long segment of ILM, as determined by light microscopy. With a minimum of 6 months of follow-up, none of these 11 eyes achieved a visual acuity of better than 20/60. Of 30 eyes that did not have ILM present, 41% achieved a visual acuity of 20/60 or better. Overall, 29% of the eyes in the entire series achieved 20/60 or better visual acuity. The difference between the group with ILM versus that without ILM was statistically significant (P = 0.01). The presence of long segments of ILM within the histopathologic specimen after vitreous surgery for removal of a macular ERM appears to indicate a less favorable visual outcome.