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1. This experiment investigated the influence of chicken PRDX3 on cell proliferation in chick embryo fibroblast cells using PRDX3 knockdown technology.2. A methyl thiazolyl tetrazolium (MTT) assay was performed to assess the effect of chPRDX3 knockdown on fibroblast proliferation. The antioxidant effect was investigated to determine if it directly mediated fibroblast cell proliferation.3. To determine the role of chPRDX3 on cell proliferation, an siRNA mediated knockdown was performed in chick fibroblast cells using an in vitro assay. The proliferation of fibroblast cells transfected with siPRDX3 #3 and siPRDX3 Mix was significantly decreased after 48 h (P < 0.01). In addition, the knockdown of chicken PRDX3 suppressed cell proliferation through an increase in oxidative stress.4. The results demonstrated that chPRDX3 is required for cell proliferation in chicken fibroblast cells. Such findings have important implications for the maintenance of chicken fibroblast cells.
Assuntos
Galinhas , Peroxirredoxina III , Animais , Proliferação de Células , Embrião de Galinha , Fibroblastos , RNA Interferente PequenoRESUMO
In this study, we compared the diagnostic accuracy and safety of fine-needle aspiration cytology and core-needle biopsy in patients with cervical lymphadenopathy or salivary gland tumour, and provided a basis for selecting the appropriate diagnostic method in clinical situations. A total of 278 patients were included in this study. The sensitivities of fine-needle aspiration cytology and core-needle biopsy were 66.7% and 100%, respectively, and negative predictive values were 92.6% and 100%, respectively, for diagnosing malignancy. In diagnosing lymphoma, fine-needle aspiration cytology gave false-negative results in all patients. In diagnosing tuberculous lymphadenopathy, the sensitivities of fine-needle aspiration cytology and core-needle biopsy were 33.3% and 91.15%, respectively, and the negative predictive values were 90.0% and 95.1%, respectively. The sensitivities of fine-needle aspiration cytology and core-needle biopsy were 42.9% and 100% in diagnosing malignant salivary gland tumours, and the negative predictive values were 91% and 100%, respectively. The results of this study showed that core-needle biopsy was superior in diagnosing and distinguishing critical diseases such as malignant lymphadenopathy and tuberculosis in patients with cervical lymphadenopathy and salivary gland tumour.
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Biópsia por Agulha Fina , Biópsia com Agulha de Grande Calibre , Linfadenopatia/patologia , Linfoma/patologia , Neoplasias das Glândulas Salivares/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Ultrasound-guided fine needle aspiration cytology (US-FNA) is useful for diagnosing cervical lymphadenopathy. However, FNA, has a high false negative rate, especially in patients with lymphoma. Ultrasound-guided core needle gun biopsy (US-CNB) has recently become important for diagnosing cancers, but its value remains undetermined. This study evaluates the efficacy of US-CNB, performed in an outpatient setting, in diagnosing cervical lymphadenopathy and the spectrum of related diseases. MATERIALS AND METHODS: This retrospective study included 79 subjects who were not squamous cell carcinoma suspects and did not have a history of malignancy between January 2006 and July 2009. A US-CNB was performed on enlarged cervical lymph nodes (>1.0cm) in all subjects. Diagnostic sensitivity, specificity, and accuracy of US-CNB in differentiating between malignant and benign lymphadenopathy were evaluated. All enrolled subjects underwent a planned US-FNA before the study US-CNB was performed. Results of US-CNB and US-FNA were compared. RESULTS: The correct histopathological diagnoses were made in 73 of 79 subjects (91.1%) using US-CNB samples. Of these, the most common diagnoses were reactive hyperplasia (26 subjects), Kikuchi's disease (17 subjects), tuberculous lymphadenitis (15 subjects), lymphoma (8 subjects), and metastatic carcinoma (3 subjects). The US-CNB was very good at differentiating between malignant and benign lymphadenopathy, with a diagnostic sensitivity, specificity, and accuracy of 91.6%, 100%, and 98.6%, respectively. Additionally, US-CNB was more accurate than US-FNA in identifying lymphoma (88.8% vs. 11.1%) and Kikuchi's disease (89.4% vs. 29.4%). No US-CNB related-complications were observed. CONCLUSION: The US-CNB is safe, effective, and has a high diagnostic yield for cervical lymphadenopathy. The US-CNB may also be useful for diagnosing lymphoma and Kikuchi's disease.
Assuntos
Biópsia com Agulha de Grande Calibre/métodos , Linfadenopatia/diagnóstico , Ultrassonografia de Intervenção , Adolescente , Adulto , Idoso , Biópsia por Agulha Fina , Criança , Feminino , Linfadenite Histiocítica Necrosante/diagnóstico , Humanos , Linfadenopatia/etiologia , Linfoma/diagnóstico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico , Pseudolinfoma/diagnóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Tuberculose dos Linfonodos/diagnóstico , Adulto JovemRESUMO
OBJECTIVE: To identify clinical factors that can explain the differences in treatment outcome, and examine the value of human papillomavirus infection as a prognostic biomarker in stage IVa tonsillar carcinomas. METHODS: Fifty-nine patients with tonsillar carcinoma classified as stage IVa were retrospectively analysed for survival outcomes according to various clinical factors. Human papillomavirus infection was evaluated using a human papillomavirus DNA chip test and immunohistochemical staining for p16 and p53. RESULTS: Lower disease-free survival rates were associated with increasing local invasiveness and nodal status. Although human papillomavirus positivity and p16 expression was more common in locally advanced tonsillar carcinomas with advanced nodal status, the overall survival rate was better for patients with human papillomavirus positive, p16-positive tumours. CONCLUSION: The disease-free survival rate may differ according to local tumour invasiveness and nodal status, even for stage IVa tonsillar cancers. Human papillomavirus infection may be a useful biomarker for predicting treatment outcomes for stage VIa tumours.
Assuntos
Carcinoma/mortalidade , Carcinoma/patologia , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/patologia , Neoplasias Tonsilares/mortalidade , Neoplasias Tonsilares/patologia , Adulto , Idade de Início , Idoso , Biomarcadores Tumorais/análise , Carcinoma/química , Carcinoma/virologia , Inibidor p16 de Quinase Dependente de Ciclina , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Papillomaviridae/isolamento & purificação , Estudos Retrospectivos , Fumar , Neoplasias Tonsilares/química , Neoplasias Tonsilares/virologia , Proteína Supressora de Tumor p53/metabolismoRESUMO
OBJECTIVE: This study aimed to evaluate the efficacy of post-operative voice therapy after phonomicrosurgery for vocal polyp removal. METHODS: The study retrospectively enrolled 55 consecutive patients who had undergone voice therapy after phonomicrosurgery for vocal polyp removal occurring between June 2010 and June 2011. A historical group of 63 similar patients not receiving voice therapy was used as an external control. We compared voice analysis parameters and Voice Handicap Index scores for the two groups. RESULTS: Most objective and subjective voice outcome parameters were significantly improved after surgical treatment. Although the study and control groups showed no significant difference regarding objective parameters (using acoustic and aerodynamic analysis) or the subjective parameters assessed using the grade-roughness-breathiness-asthenia-strain scale, the study group had significantly better final Voice Handicap Index scores. CONCLUSION: Following surgery for vocal polyps, post-operative voice therapy can improve patients' vocal discomfort, emotional responses and everyday self-perception.
Assuntos
Doenças da Laringe/cirurgia , Pólipos/cirurgia , Prega Vocal/cirurgia , Treinamento da Voz , Estudos de Casos e Controles , Feminino , Humanos , Doenças da Laringe/reabilitação , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Pólipos/reabilitação , Cuidados Pós-Operatórios/métodos , Estudos Prospectivos , Resultado do TratamentoRESUMO
The objective of this study was to use fluorescence-activated cell sorting (FACS) and spermatogonial stem cell (SSC) xenotransplantation to identify cell surface markers of putative porcine SSC. Analysis of porcine testis cells enriched for spermatogonia using FACS indicated that nearly half of stage-specific embryonic antigen-1 (SSEA-1) expressing testis cells expressed the undifferentiated spermatogonia marker protein gene product 9.5 (PGP 9.5) whereas significantly fewer (P < 0.05) cells selected for thymus cell antigen-1 (Thy-1), also known as cluster of differentiation 90 (CD90), cluster of differentiation 9 (CD9), or other SSC markers expressed PGP 9.5. Immunocytochemical analysis indicated that promyelocytic leukemia zinc finger (PLZF) protein and germ cell lineage marker VASA homolog (VASA), also known as DEAD box protein 4 (DDX4), were expressed by SSEA-1 expressing germ cells. Spermatogonial stem cell xenotransplantation of testis cell populations enriched for cells expressing SSEA-1 generated significantly (P < 0.05; greater than 15-fold) more colonies of donor derived germ cells than unselected testis cells. In conclusion, these data indicate that SSC markers identified in rodents are likely not entirely conserved in pigs and that SSEA-1 is a marker for porcine undifferentiated spermatogonia including SSC in prepubertal boars and its expression may serve as a target for the further study of porcine germ cells.
Assuntos
Células-Tronco Adultas/metabolismo , Regulação da Expressão Gênica , Antígenos CD15/genética , Sus scrofa/genética , Testículo/metabolismo , Células-Tronco Adultas/citologia , Animais , Biomarcadores , Citometria de Fluxo , Antígenos CD15/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Sus scrofa/crescimento & desenvolvimento , Sus scrofa/metabolismo , Testículo/citologia , Testículo/crescimento & desenvolvimento , Transplante HeterólogoRESUMO
OBJECTIVE: Despite extensive efforts to raise awareness, Papanicolaou (Pap) testing rates among Chinese women living in North America remain low compared with Euro-American women. Although the lower Pap testing rate and ensuing health repercussions among Chinese women are well characterized, mechanisms underlying such health disparities are not. The aim of this study was to use a qualitative approach to delineate such mechanisms. Qualitative approaches to understand constructs within the domain of sexual and reproductive health have been shown to be particularly appropriate, and offer a nuanced view of sexuality that is not afforded by traditional quantitative methods. METHOD: We carried out two focus groups aimed at exploring how Mandarin-speaking and English-speaking Chinese women experience Pap testing (N = 12). The women were invited to partake in the focus groups from having participated in a large-scale quantitative study. Participants were all first-generation immigrants and their average age was 53-years-old. We used content analyses to analyze transcripts and extract themes. RESULTS AND DISCUSSION: The women heavily endorsed traditional Chinese medicine philosophy, conceptualizing physical health holistically, and valuing preventative measures over screening and interceptive measures. Pap testing was described as qualitatively different from other screening procedures, such that women assigned a sexually charged meaning to Pap testing, often discussing it in relation to sexual activity and promiscuity. Women expressed their preference for the compulsory and depersonalized manner that Pap tests are performed in their home country of China, as this lessens the embarrassment associated with undergoing Pap testing. CONCLUSION: Three mechanisms may contribute to lower Pap testing among middle-aged first-generation Chinese immigrants: preference for Chinese medicine philosophy, perceived sexualization of Pap testing, and the institutionalization of medical care. Implications for improving the reproductive health of Chinese women are discussed.
RESUMO
Clotrimazole, a poorly water-soluble antimycotic agent, is a promising therapeutic agent for various diseases including cancer and sickle cell anemia. The oral bioavailability and hepatic toxicity of clotrimazole were compared with its beta-cyclodextrin inclusion form which was prepared by the spray-drying method. The inclusion complex gave significantly higher initial plasma concentrations, Cmax and AUC than did clotrimazole alone, indicating that the drug from the inclusion compound could be more easily absorbed in rats. Furthermore, mice treated with the inclusion compound showed significantly higher GOT/GPT values compared to clotrimazole alone. The inclusion compound also induced hypertrophy of hepatic cells by fat accumulation and disappearance of hepatic sinusoids, indications of pathological changes of liver, suggesting that the inclusion compound could induce more severe tissue damage in the liver than clotrimazole alone. Thus, hepatotoxicity of clotrimazole seems to be correlated with the enhanced oral bioavailability by inclusion complexation. Our results suggest that, in the development of a novel oral product, appearance or enhancement of hepatic toxicity must be considered along with oral bioavailability.
Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Clotrimazol/administração & dosagem , Clotrimazol/farmacocinética , beta-Ciclodextrinas/química , Alanina Transaminase/sangue , Animais , Antifúngicos/toxicidade , Área Sob a Curva , Aspartato Aminotransferases/sangue , Química Farmacêutica , Clotrimazol/toxicidade , Portadores de Fármacos , Meia-Vida , Fígado/patologia , Testes de Função Hepática , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pós , Ratos , Ratos Sprague-Dawley , SolubilidadeRESUMO
The purpose of this study was to prepare microspheres loaded with hydrophilic drug, bupivacaine HCl using poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). Microspheres were prepared with varying the PLGA/PLLA ratio with two different levels of bupivacaine HCl (5 and 10%) using a supercritical anti-solvent (SAS) technique. Microspheres ranging from 4-10 microm in geometric mean diameter could be prepared, with high loading efficiency. Powder X-ray diffraction (PXRD) revealed that bupivacaine HCl retained its crystalline state within the polymer and was present as a dispersion within the polymer phase after SAS processing. The release of bupivacaine HCl from biodegradable polymer microspheres was rapid up to 4 h, thereafter bupivacaine HCl was continuously and slowly released for at least 7 days according to the PLGA/PLLA ratio and the molecular weight of PLLA.
Assuntos
Bupivacaína/administração & dosagem , Microesferas , Implantes Absorvíveis , Materiais Biocompatíveis/química , Precipitação Química , Preparações de Ação Retardada/administração & dosagem , Composição de Medicamentos/métodos , Ácido Clorídrico/química , Ácido Láctico/química , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Poliésteres , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/química , Solventes/química , Propriedades de Superfície , Difração de Raios XRESUMO
Thyroid hemiagenesis is a rare abnormality in which one thyroid lobe fails to develop. Most of the patients diagnosed have an associated thyroid disease. We report the case of a 32-year-old woman who presented with a left thyroid mass which had been gradually increasing in size over a period of two years. A thyroid scan revealed the absence of the right thyroid lobe and isthmus, and a hypoactive nodule was evident in the lower pole of the left lobe. Ultrasonography confirmed the right lobe and the isthmus agenesis. The operative findings confirmed hemiagenesis of the right lobe and nodular hyperplasia in the left lobe. The purpose of this report is to present a patient with hemiagenesis of the thyroid gland who concomitantly had nodular hyperplasia; we also stress the importance of pre-operative differentiation between benign lesions and malignancy in order to aid critical decision making and to facilitate preservation of thyroid function if possible.
Assuntos
Glândula Tireoide/anormalidades , Neoplasias da Glândula Tireoide/complicações , Adulto , Feminino , Humanos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Resultado do Tratamento , UltrassonografiaRESUMO
We investigated the clinical analysis of non-Hodgkin's lymphoma (NHL) of the sinonasal tract, including the survival rate and treatment outcome. Fifty patients who had previously received a diagnosis of extranodal NHL of the sinonasal cavity from May 1992 to April 2001 were included. We reviewed the patients' clinical characteristics and the survival rates, retrospectively. Of 50 patients, 49 were classified as having extranodal NK/T cell lymphoma and only one patient as having diffuse large B cell (DLBC) lymphoma according to the new WHO classification. Even though higher mortality rates were observed in patients receiving chemotherapy alone than in those receiving chemotherapy and radiation therapy in the advanced stage, the combination treatment of chemotherapy and radiation therapy failed to demonstrate a significantly higher survival rate.
Assuntos
Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Neoplasias dos Seios Paranasais/mortalidade , Neoplasias dos Seios Paranasais/terapia , Seios Paranasais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biópsia por Agulha , Terapia Combinada , Feminino , Humanos , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias dos Seios Paranasais/patologia , Probabilidade , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
The interactions between B-cell lymphoma 2 (BCL-2) family members are known to be mediated through the binding of the BH3 domain of a proapoptotic member to the BH3-binding groove of an antiapoptotic member. We determined the crystal structure of antiapoptotic CED-9, which reveals a unique C-terminal helix altering the common BH3-binding region. A coexpression system to produce CED-9 in complex with proapoptotic EGL-1 enabled us to show that the binding of EGL-1 to CED-9 is extremely stable, raising the melting temperature (T(M)) of CED-9 by 25 degrees C, and that the binding surface of CED-9 extends beyond the BH3-binding region and reaches the BH4 domain. Consistently, the T(M) and a 1H-15N correlation NMR spectrum of CED-9 in complex with EGL-1 are drastically different from those of CED-9 in complex with the EGL-1 BH3 peptide. The data suggest that the recognition between other BCL-2 family members may also involve much wider protein surfaces than is previously thought.
Assuntos
Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas/química , Proteínas Repressoras/metabolismo , Animais , Apoptose , Proteínas Reguladoras de Apoptose , Dicroísmo Circular , Cristalografia por Raios X , Escherichia coli/metabolismo , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Peptídeos/química , Plasmídeos/metabolismo , Mutação Puntual , Ligação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas/química , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Recombinantes/química , Proteínas Repressoras/química , TemperaturaRESUMO
Internal mammary artery angiography is increasingly required, but the technique for left internal mammary artery (LIMA) angiography during right transradial coronary angiography is not well established. The authors investigated the feasibility and safety of a new, simple, and rapid nonselective technique. Following right transradial coronary angiography, LIMA angiography was performed using a 5 French (Fr) Judkins JL-3.5 catheter in 110 patients. The catheter, placed in the ascending aorta with its natural curve, was withdrawn slowly while being rotated clockwise to engage its tip in the proximal left subclavian artery. Contrast material was injected while sphygmomanometer cuff inflation was applied to the left upper arm. In the last 50 patients, the angiography was performed twice randomly with and without the cuff inflation. In 108 patients (98%), the catheter was successfully engaged in the subclavian artery in a mean of 11 +/- 8 seconds (range, 3-136) from the time when it was withdrawn from the ascending aorta, and nonselective LIMA angiography was successfully performed. The image quality of the angiograms was satisfactory in 103 (95%) of the 108 patients. In the last 50 patients, the image quality of the angiograms was determined satisfactory in 48 (96%) and 45 (90%) patients, with and without the cuff inflation, respectively. The difference was statistically not significant. There were no complications, including arterial dissection and thromboembolism. In conclusion, nonselective LIMA angiography can be readily and safely performed during right transradial coronary angiography using a 5 Fr Judkins JL-3.5 catheter.
Assuntos
Artéria Torácica Interna/diagnóstico por imagem , Idoso , Angiografia/métodos , Cateterismo Cardíaco , Angiografia Coronária , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Total circulatory arrest with full venous drainage can result in air entering the arterial system through several possible sites such as the aortic cannulation site or collateral vessels. Air present in the arterial system during total circulatory arrest imposes a special problem. We describe a simple technique of short-term retrograde systemic perfusion to remove air from the arterial system before restarting systemic arterial perfusion after total circulatory arrest.
Assuntos
Doenças da Aorta/terapia , Enfisema/terapia , Parada Cardíaca Induzida/efeitos adversos , Perfusão , Humanos , Lactente , MasculinoRESUMO
Previous studies have demonstrated that levels of tumor necrosis factor-alpha (TNF-alpha) or its mRNA expression are increased in acute renal failure of various types including ischemia/reperfusion injury. This study was undertaken to determine whether pentoxifylline (PTX), an inhibitor of TNF-alpha production, provides a protective effect against ischemic acute renal failure in rabbits. Renal ischemia was induced by clamping bilateral renal arteries for 60 min. Animals were pretreated with PTX (30 mg/kg, i.v.) 10 min before release of clamp. At 24 h of reperfusion of blood after ischemia, changes in renal function, renal blood flow, and the expression of TNF-alpha mRNA were evaluated. Ischemia/reperfusion caused a marked reduction in GFR, which was accompanied by an increase of serum creatinine levels. Such changes were significantly attenuated by PTX pretreatment. PTX ameliorated the impairment of renal tubular function, but it had no effect on the reduction of renal blood flow induced by ischemia/reperfusion. The protective effect of PTX on functional changes was supported by morphological studies. The impairment of glucose and phosphate reabsorption in postischemic kidneys was associated with a depression in the expression of Na+-glucose and Na+-Pi transporters. The expression of TNF-alpha mRNA was increased after reperfusion, which was inhibited by PTX pretreatment. The PTX pretreatment in vitro prevented the release of lactate dehydrogenase induced by an oxidant t-butylhydroperoxide in rabbit renal cortical slices, but it did not produce any effect on the oxidant-induced lipid peroxidation, suggesting that PTX protection is not resulted from its antioxidant action. These results suggest that PTX may exert a protective effect against ischemic acute renal failure by inhibiting the production of TNF-alpha in rabbits.
Assuntos
Injúria Renal Aguda/prevenção & controle , Pentoxifilina/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/metabolismo , Animais , Depressão Química , Rim/metabolismo , Masculino , Proteínas de Transporte de Monossacarídeos/metabolismo , Pentoxifilina/uso terapêutico , RNA Mensageiro/metabolismo , Coelhos , Traumatismo por Reperfusão/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This study was undertaken to examine the role of lipid peroxidation and poly(ADP-ribose) polymerase (PARP) activation in H(2)O(2)-induced inhibition of Na(+)-dependent phosphate (Na(+)-Pi) uptake in opossum kidney (OK) cells. H(2)O(2) inhibited Na(+)-Pi uptake in a dose-dependent manner. H(2)O(2)-induced inhibition of Na(+)-Pi uptake was prevented by dithiothreitol and glutathione. A potent antioxidant, DPPD, had no effect on H(2)O(2) inhibition of Na(+)-Pi uptake, despite completely inhibiting lipid peroxidation induced by H(2)O(2). However, in primary cultured rabbit proximal tubular cells, the effect of H(2)O(2) on Na(+)-Pi uptake was significantly prevented by DPPD, suggesting a species difference in the role of lipid peroxidation in the inhibition of Na(+)-Pi uptake occurring with H(2)O(2). t-Butylhydroperoxide (tBHP) caused the inhibition of Na(+)-Pi uptake that was prevented by DPPD in OK cells and rabbit proximal tubular cells. The PARP inhibitor 3-aminobenzamide completely protected the inhibition of Na(+)-Pi uptake induced by H(2)O(2) but not by tBHP. H(2)O(2)-induced ATP depletion was prevented by 3-aminobenzamide but not by DPPD. tBHP-induced ATP depletion was prevented by DPPD, whereas it was not altered by 3-aminobenzamide. Effects of H(2)O(2) and tBHP on Na(+)-Pi uptake and ATP depletion were prevented by an iron chelator, deferoxamine, suggesting that the oxidants inhibit Na(+)-Pi uptake through an iron-dependent mechanism. The extent of DNA damage by tBHP was similar to that by H(2)O(2). These results indicate that the effect of H(2)O(2) on membrane transport function in OK cells is associated with PARP activation but not lipid peroxidation, whereas the effect of tBHP is associated with lipid peroxidation.
Assuntos
Peróxido de Hidrogênio/toxicidade , Rim/efeitos dos fármacos , Peroxidação de Lipídeos , Poli(ADP-Ribose) Polimerases/fisiologia , Animais , Benzamidas/farmacologia , Transporte Biológico/efeitos dos fármacos , Células Cultivadas , Ditiotreitol/farmacologia , Ativação Enzimática , Glutationa/farmacologia , Rim/metabolismo , Gambás , Fosfatos/metabolismo , Coelhos , Sódio/metabolismoRESUMO
A reduction in glomerular filtration rate (GFR) is a primary characteristic of ischemic acute renal failure. The present study was undertaken to examine the roles of angiotensin II, tubuloglomerular-feedback (TGF) mechanism, and tubular obstruction for the GFR reduction in the post-ischemic kidney. Renal ischemia was induced by occlusion of the bilateral renal arteries for 60 min, and renal function was examined at 2 and 24 h after the onset of reflow. After the end of 2-h reflow, the GFR was not significantly changed, but the urine flow increased significantly. On the other hand, at the end of 24-h reflow, the GFR and urine flow decreased markedly along with increased filtration fraction. The renal blood flow significantly decreased at 24 h, but not 2 h, after reflow, which was accompanied by increased total renal vascular resistance. Furosemide infusion (1 mg/min/kg) after 24 h of reflow prevented the reduction in GFR and filtration fraction without no changes in renal blood flow and total renal vascular resistance. Pretreatment of enalapril and losartan did not prevent the reduction in GFR, indicating that angiotensin II was not involved. In morphological examinations, tubular obstruction was seen in the proximal and distal tubules of kidneys both at 2 and 24 h after the onset of reflow. In two rabbits subjected to 48 h of reflow, the tubular obstruction was not observed, despite GFR remained depressed. These results suggest that the late reduction in GFR in postischemic kidneys is not mediated by angiotensin II, but is mediated, at least in part, by the TGF mechanism. The tubular obstruction may be not prerequisite for the GFR reduction in rabbits.
Assuntos
Injúria Renal Aguda/fisiopatologia , Taxa de Filtração Glomerular/fisiologia , Isquemia/fisiopatologia , Rim/irrigação sanguínea , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/prevenção & controle , Angiotensina II/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Biomarcadores , Creatinina/metabolismo , Enalapril/farmacologia , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Isquemia/complicações , Isquemia/metabolismo , Isquemia/prevenção & controle , Rim/efeitos dos fármacos , Rim/metabolismo , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Losartan/farmacologia , Masculino , Coelhos , Circulação Renal , UrodinâmicaRESUMO
The present study was undertaken to examine the role of arachidonic acid (AA) metabolites in hypoxia/reoxygenation (H/R)-induced renal cell injury in rabbit renal cortical slices using AA metabolic inhibitors. Inhibitors of cyclooxygenase (indomethacin and diclofenac sodium) and lipoxygenase pathways (nordihydroguaiaretic acid, caffeic acid, and eicosapentaenoic acid) reduced H/R-induced LDH release in a dose-dependent manner, whereas an inhibitor of cytochrome P-450 monooxygenase pathway ethoxyresorufin was not effective. AA increased LDH release in control slices, and the effect was not altered by indomethacin and nordihydroguaiaretic acid. The protective effect of indomethacin was not affected by addition of PGE2, a main product of cyclooxygenase pathway in the kidney. H2O2-induced LDH release was prevented by inhibitors of lipoxygenase but not by inhibitors of cyclooxygenase and cytochrome P-450 monooxygenase H/R-induced LDH release was not altered by iron chelators, phenanthroline and deferoxamine, and a potent antioxidant, N,N'-diphenyl-p-phenylenediamine, suggesting that the H/R-induced cell injury is not attributed to a generation of reactive oxygen species. Morphological studies showed that H/R-induced structural changes including cell necrosis were significantly prevented by indomethacin. These results suggest that inhibitors of cyclooxygenase and lipoxygenase pathways exert a direct protective effect against the H/R-induced cell injury in renal tubules. Whether these effects are mediated by alterations of AA metabolic pathways is not certain.
Assuntos
Ácido Araquidônico/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Hipóxia/prevenção & controle , Córtex Renal/efeitos dos fármacos , Nefropatias/prevenção & controle , Inibidores de Lipoxigenase/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Antioxidantes/farmacologia , Inibidores das Enzimas do Citocromo P-450 , Dinoprostona/farmacologia , Relação Dose-Resposta a Droga , Hipóxia/metabolismo , Hipóxia/patologia , Quelantes de Ferro/farmacologia , Córtex Renal/metabolismo , Córtex Renal/patologia , Nefropatias/metabolismo , Nefropatias/patologia , L-Lactato Desidrogenase/metabolismo , Masculino , Coelhos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
Superoxide dismutase has been known to play a role as an anti-oxidative system against oxidative injury during acute inflammation. To investigate the role of superoxide dismutase in eustachian tubal mucosa during acute otitis media (AOM), an animal model was made. Sprague-Dawley rats were inoculated with Streptococcus pneumoniae through the nasal cavity following development of virus-induced upper respiratory infection. The animals were divided into three groups according to their tympanic cavity conditions following bacterial inoculation; inoculated animals with no resultant AOM (no-AOM), animals with resultant AOM (AOM) and animals with resolving otitis media (recovery). The changes of superoxide dismutase in each tubal mucosa were compared with that of the normal control using immunohistochemistry and immunoblotting methods. On Western blot, there were little changes of optical density and surface area in no-AOM (213.5 +/- 22.4, 13.2 +/- 0.8 mm2) and recovery group (219.3 +/- 18.7, 14.8 +/- 0.7 mm2) compared to the normal control (223.5 +/- 26.2, 16.7 +/- 0.4 mm2). However, a marked decrease was found in the AOM model (167.6 +/- 19.3, 6.5 +/- 0.9 mm2). These findings suggest that superoxide dismutase may play a role in protecting tubal mucosa from free radical injury during AOM.
Assuntos
Tuba Auditiva/enzimologia , Otite Média/enzimologia , Infecções Pneumocócicas/enzimologia , Infecções Respiratórias/complicações , Superóxido Dismutase/fisiologia , Doença Aguda , Animais , Técnicas Imunoenzimáticas , Mucosa Nasal/enzimologia , Otite Média/complicações , Infecções Pneumocócicas/complicações , Ratos , Ratos Sprague-DawleyRESUMO
In an attempt to improve the skin penetration of ketoprofen, various transdermal formulations were prepared, and their in vitro skin permeability and in vivo percutaneous absorption were evaluated. In vitro permeation studies were performed using a modified Franz cell diffusion system in which permeation parameters such as cumulative amount at 8 hr Q8hr, steady-state flux Jss, or lag time tL were determined. In the in vivo percutaneous absorption study using the hairless mouse, maximum concentration Cmax and area under the curve at 24 hr AUC24h were measured. The optimal transdermal formulation (oleo-hydrogel formulation) of ketoprofen showed a Q8hr value of 227.20 micrograms/cm2, a Jss value of 29.61 micrograms/cm2/hr, and a tL value of 0.46 hr. The Q8hr and Jss values were about 10-fold (p < .01) higher than those (Q8hr = 19.61 micrograms/cm2; Jss = 2.66 micrograms/cm2/hr) from the K-gel and about 3.5-fold (p < .01) than those (Q8hr = 60.00 micrograms/cm2; Jss = 7.99 micrograms/cm2/hr) of the K-plaster. In the in vivo percutaneous absorption, the Cmax (6.82 micrograms/ml) and AUC24h (55.74 micrograms.hr/ml) values of the optimal formulation were significantly (p < .01) higher than those of K-gel and K-plaster. The relative bioavailability of the oleo-hydrogel following transdermal administration in reference to oral administration was about 37%, and the Cmax value (4.73 micrograms/cm2) in the hypodermis following topical administration was much higher than those from the conventional products (Cmax of K-gel and K-plaster were 0.92 +/- 0.19 microgram/cm2 and 1.27 +/- 0.37 microgram/cm2, respectively). These data demonstrate that the oleo-hydrogel formulation of ketoprofen was more beneficial than conventional products (K-gel and K-plaster) in enhancing transdermal permeation and skin absorption of ketoprofen. Furthermore, there was a good correlation between in vitro permeation parameters and in vivo percutaneous absorption parameters.