Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Inflammation ; 35(1): 297-307, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21468627

RESUMO

We investigated whether interleukin-4 (IL-4) is present and capable of reducing inflammatory changes seen in ifosfamide-induced hemorrhagic cystitis. Male Swiss mice were treated with saline or ifosfamide alone or ifosfamide with the classical protocol with mesna and analyzed by changes in bladder wet weight (BWW), macroscopic and microscopic parameters, exudate, and hemoglobin quantification. In other groups, IL-4 was administered intraperitoneally 1 h before ifosfamide. In other experimental groups, C57BL/6 WT (wild type) and C57BL/6 WT IL-4 (-/-) knockout animals were treated with ifosfamide and analyzed for changes in BWW. Quantification of bladder IL-4 protein by ELISA in control, ifosfamide-, and mesna-treated groups was performed. Immunohistochemistry to tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) as well as protein identification by Western blot assay for inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was carried out on ifosfamide- and IL-4-treated animals. In other experimental groups, antiserum against IL-4 was given 30 min before ifosfamide. In IL-4-treated animals, the severity of hemorrhagic cystitis was significantly milder than in animals treated with ifosfamide only, an effect that was reverted with serum anti-IL-4. Moreover, knockout animals for IL-4 (-/-) exhibit a worse degree of inflammation when compared to C57BL/6 wild type. Exogenous IL-4 also attenuated TNF-α, IL-1ß, iNOS, and COX-2 expressions in ifosfamide-treated bladders. IL-4, an anti-inflammatory cytokine, attenuates the inflammation seen in ifosfamide-induced hemorrhagic cystitis.


Assuntos
Cistite/tratamento farmacológico , Ifosfamida/toxicidade , Interleucina-4/metabolismo , Interleucina-4/farmacologia , Bexiga Urinária/patologia , Animais , Ciclo-Oxigenase 2/biossíntese , Cistite/induzido quimicamente , Cistite/patologia , Hemorragia , Interleucina-1beta/biossíntese , Interleucina-4/imunologia , Masculino , Mesna/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo II/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Bexiga Urinária/metabolismo
2.
Congest Heart Fail ; 17(2): 85-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21449997

RESUMO

The authors sought to obtain objective evidence for impacting the American College of Cardiology Heart Failure Guidelines for the routine use of serial echocardiography by assessing the reliability of the use of clinician-assessed patient symptoms and New York Heart Association (NYHA) functional classification compared with ejection fraction (EF) measured by echocardiography. A prospective study in 256 patients with systolic heart failure (HF) enrolled into an HF disease management program with EF ≤40% and at least 2 annual echocardiograms were included. Only 86 of 256 (33.5%) patients were correctly classified by NYHA class as showing improvement, no change, or deterioration as compared with echocardiographic assessments. Patients whose NYHA class showed no change between echocardiograms had the lowest survival rate. Quantification in patient's status with NYHA classification is not always a reliable assessment to evaluate prognosis and guide medical therapy for patients with systolic HF.


Assuntos
Ecocardiografia/métodos , Insuficiência Cardíaca Sistólica/diagnóstico por imagem , Guias de Prática Clínica como Assunto , Feminino , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Sístole
3.
J Sex Med ; 6(7): 1999-2007, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19453910

RESUMO

INTRODUCTION: Seventy percent to 90% of patients with heart failure (HF) report erectile problems. There are no published data on whether erectile dysfunction (ED) and peripheral vascular disease (PVD) correlate with mortality in HF patients. Also, little is known regarding the impact of HF etiology on mortality in patients with ED. AIMS: Our aim was to investigate the relationship between ED and mortality in HF patients, to evaluate whether the etiology of HF carries a prognostic measure in patients with ED, and to assess the impact of PVD on mortality in optimally treated HF patients with ED. MAIN OUTCOME MEASURES: The measures are: (i) mortality by presence or absence of ED; (ii) mortality by HF etiology and presence or absence of ED; and (iii) PVD and mortality in HF patients on optimal medical therapy with ED. METHODS: This is a single-center, prospective cohort study of 328 male HF patients (ejection fraction < or = 40%) followed while being treated with optimal doses of beta blockers and angiotensin-converting enzyme inhibitors. The Sexual Health Inventory for Men survey was used to assess ED (no ED > or = 22 and ED < or = 21). Ankle brachial index (ABI) was used to assess PVD (normal ABI > or = 0.9 and abnormal ABI < 0.9). RESULTS: Kaplan-Meier curves were constructed to examine the relationship between the presence or absence of ED and PVD, and mortality in a HF population. Although not statistically significant, a trend for increased risk of death was demonstrated in the ischemic cardiomyopathy cohort with ED. CONCLUSIONS: ED, highly prevalent in this cohort, did not identify HF patients on optimal medical therapy at increased risk for mortality. Among the HF patients with ED, HF type was not associated with increased risk for mortality whereas PVD was independently associated with a statistically significant increase in mortality.


Assuntos
Insuficiência Cardíaca/mortalidade , Impotência Vasculogênica , Doenças Vasculares Periféricas , Antagonistas Adrenérgicos beta , Inibidores da Enzima Conversora de Angiotensina , Índice Tornozelo-Braço , Inquéritos Epidemiológicos , Insuficiência Cardíaca/epidemiologia , Hemodinâmica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Razão de Chances , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/epidemiologia
4.
Exp Toxicol Pathol ; 59(6): 425-30, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18234483

RESUMO

AIM: Acrolein (ACR) is a urinary metabolite of cyclophosphamide (CPS) and ifosfamide (IFS), which has been demonstrated to be the causative agent of hemorrhagic cystitis (HC), induced by these compounds. In this study, we investigate the participation of cyclooxygenase-2 (COX-2) on ACR-induced HC. METHODS: Male Wistar rats (150-200g; six rats per group) were treated with distilled water or intravesical ACR and analyzed by changes in bladder wet weight, macroscopic and microscopic parameters and COX-2 expression. RESULTS: COX-2 immunohistochemical expression was significant 12h after ACR administration mainly in subepithelial cells. ACR injection also alters some macroscopic and microscopic parameters in bladder of rats analyzed by Gray's criteria. CONCLUSIONS: COX-2 participates in the pathogenesis of ACR-induced HC first seen 12h after initial contact between ACR and urothelium.


Assuntos
Acroleína/toxicidade , Ciclo-Oxigenase 2/biossíntese , Cistite/induzido quimicamente , Hemorragia/induzido quimicamente , Acroleína/metabolismo , Administração Intravesical , Animais , Cistite/complicações , Cistite/enzimologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Indução Enzimática , Hemorragia/complicações , Hemorragia/enzimologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Fatores de Tempo , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/enzimologia , Bexiga Urinária/patologia
5.
J Cancer Res Clin Oncol ; 134(1): 19-27, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17638016

RESUMO

PURPOSE: Hemorrhagic cystitis (HC) is a limiting side effect of chemotherapy with ifosfamide (IFS). In this study, we investigated the participation of cyclooxygenase-2 (COX-2) upon ifosfamide-induced HC. METHODS: Male Wistar rats (150-200 g; six rats per group) were treated with saline, IFS (400 mg/kg, i.p.) and analyzed by changes in bladder wet weight, macroscopic and microscopic parameters, and COX-2 expression. In other groups etoricoxib (selective COX-2 inhibitor), indomethacin (non-selective COX inhibitor), thalidomide (selective TNF-alpha inhibitor), pentoxifyllin (non-selective TNF-alpha inhibitor) were added 1 h before IFS administration. The classical protocol using three doses of Mesna was also evaluated and compared with two extra doses of etoricoxib or indomethacin. RESULTS: COX-2 was expressed significantly 24 h after IFS administration mainly in myofibroblasts and mast cells evaluated by immunohistochemistry. Treatment 1 h before IFS injection with etoricoxib, indomethacin, thalidomide, and pentoxifylline reduced COX-2 expression and some macroscopic and microscopic parameters in IFS-induced HC. Moreover, addition of etoricoxib or indomethacin with the last two doses of Mesna was more efficient than three doses of Mesna alone when evaluated microscopically. CONCLUSIONS: COX-2 participates in the pathogenesis of IFS-induced HC and the treatment with COX and TNF-alpha inhibitors reduced COX-2 expression. The addition of COX-inhibitors to the last two doses of Mesna represents a new therapeutic strategy of preventing HC.


Assuntos
Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Cistite/enzimologia , Hemorragia/enzimologia , Ifosfamida/efeitos adversos , Animais , Cistite/induzido quimicamente , Cistite/patologia , Quimioterapia Combinada , Etoricoxib , Hemorragia/induzido quimicamente , Hemorragia/patologia , Técnicas Imunoenzimáticas , Indometacina/uso terapêutico , Masculino , Mesna/uso terapêutico , Pentoxifilina/uso terapêutico , Substâncias Protetoras/uso terapêutico , Piridinas/uso terapêutico , Ratos , Ratos Wistar , Sulfonas/uso terapêutico , Talidomida/uso terapêutico
6.
Cancer Chemother Pharmacol ; 59(5): 643-50, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16947012

RESUMO

PURPOSE: Hemorrhagic cystitis (HC) is a limiting side effect of chemotherapy with ifosfamide (IFS). Mesna is the drug of choice for prevention of HC. In this study, we analyzed cystoscopic and histological changes present in bladders of patients using IFS with mesna prophylaxis. METHODS: Thirty-three patients selected for IFS plus three doses of mesna chemotherapy regime were assigned at random to two groups: Group I or reference group consisted of 18 patients yet untreated. Group II consisted of 15 patients in whom urinalysis and cystoscopy plus vesical biopsy were performed only 24 h after receiving the last dose of IFS. The cystoscopic and histological findings were used as parameters for evaluating the results. For the former the criterion adopted was macroscopic vesical changes in accordance with Gray's criteria. Histological analyses were performed by evaluation method especially adapted to this study. RESULTS: Even under treatment with three doses of mesna, 66.7% of patients presented cystoscopic alterations and 100% showed bladder mucosa microscopic alterations such as edema, exocytosis, and hemorrhage. CONCLUSIONS: The standard protocol used for prevention of IFS-induced HC with three doses of mesna does not completely prevent bladder damage. The histopathological criteria used in this study for observation of inflammatory events allowed staging the intensity of IFS-induced urothelial and mucosal injury.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Ifosfamida/efeitos adversos , Mesna/uso terapêutico , Doenças da Bexiga Urinária/induzido quimicamente , Doenças da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Adolescente , Adulto , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Cistoscopia , Edema/induzido quimicamente , Edema/patologia , Eritrócitos/efeitos dos fármacos , Etoposídeo/uso terapêutico , Exocitose/efeitos dos fármacos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/patologia , Humanos , Ifosfamida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Urotélio/patologia
7.
Int J Urol ; 10(11): 595-602, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14633084

RESUMO

AIM: Hemorrhagic cystitis (HC) is a limiting side-effect of chemotherapy with ifosfamide (IFS). In the study presented here, we investigated the use of dexamethasone in combination with mesna for the prevention of IFS-induced HC. METHODS: Male Wistar rats (150-200 g; 6 rats per group) were treated with saline or mesna 5 min (i.p.) before and 2 and 6 h after (v.o.) administration of IFS. One, two or three doses of mesna were replaced with dexamethasone alone or with dexamethasone plus mesna. Cystitis was evaluated 24 h after its induction by the changes in bladder wet weight and by macroscopic and microscopic analysis. RESULTS: The replacement of the last dose or the last two doses of mesna with dexamethasone reduced the increase in bladder wet weight induced by IFS by 84.79% and 89.13%, respectively. In addition, it almost abolished the macroscopic and microscopic alterations induced by IFS. Moreover, the addition of dexamethasone to the last two doses of mesna was more efficient than three doses of mesna alone when evaluated microscopically. CONCLUSION: Dexamethasone in combination with mesna was efficient in blocking IFS-induced HC. However, the replacement of last two doses of mesna with saline or all of the mesna doses with dexamethasone did not prevent HC.


Assuntos
Anti-Inflamatórios/administração & dosagem , Cistite/tratamento farmacológico , Dexametasona/administração & dosagem , Hemorragia/tratamento farmacológico , Ifosfamida/efeitos adversos , Mesna/administração & dosagem , Substâncias Protetoras/uso terapêutico , Animais , Cistite/induzido quimicamente , Cistite/patologia , Cistite/prevenção & controle , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Hemorragia/patologia , Hemorragia/prevenção & controle , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Cloreto de Sódio/administração & dosagem , Resultado do Tratamento , Bexiga Urinária/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...