RESUMO
Clindamycin is used for infections caused by Gram-positive and Gram-negative anaerobic pathogens and Gram-positive aerobes. Propionibacterium acnes is an important opportunistic microorganism of the human skin and is related to prostatitis. An LC-electrospray ionization-quadrupole time-of-flight-MS method was validated for determining clindamycin concentrations in plasma and prostate microdialysate. Clindamycin separation was carried out on a C18 column at 0.5 mL/min. The mobile phase employed gradient elution of formic acid and methanol. A mass spectrometer was operated in positive electrospray ionization mode to monitor ion 425.1784 and 253.1152 for clindamycin and cimetidine (internal standard), respectively. Linearity was obtained at 0.5-10.0 µg/mL (plasma) and 0.05-1.0 µg/mL (microdialysate) with coefficients of determination ≥0.999. The intra- and inter-day precision (coefficient of variation - CV%) values were ≤13.83% and 12.51% for plasma, respectively, and ≤10.90% and 9.35% for microdialysate, respectively. The accuracy was between 90.82% and 108.25% for plasma, and 96.97% and 106.98% for microdialysate. The present method was fully validated and applied to investigate clindamycin concentrations in both plasma and prostate by microdialysis in Wistar rats (80 mg/kg, intravenous). Because the penetration of antibiotics into the prostate may be restricted, this method allows us to investigate the prostate concentrations of clindamycin for the first time.
Assuntos
Cromatografia Líquida/métodos , Clindamicina/análise , Próstata/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Clindamicina/química , Clindamicina/farmacocinética , Limite de Detecção , Modelos Lineares , Masculino , Microdiálise , Próstata/metabolismo , Ratos , Ratos Wistar , Reprodutibilidade dos TestesRESUMO
The aim of this study was to assess the volumetric density (Vv) of the fibronectin in the periurethral region of patients with benign prostatic hyperplasia (BPH) and compare with a control group. Prostatic periurethral tissue samples were obtained from ten patients (age range 65 to 79 years, mean 66) with clinical symptoms of bladder outlet obstruction who had undergone open prostatectomy. The control group samples (periurethral tissue samples from the transitional zone) were collected from prostates obtained during autopsy of accidental death adults of less than 25 years. The volumetric density (Vv) of the fibronectin was determined with stereological methods from 25 random fields per sample using the point-count method with an M-42 grid test system. The quantitative data were analyzed using the Kolmogorov-Smirnov and Mann-Whitney U tests. The Vv in the control and BPH groups was 21.9% ± 1.5% and 29.1% ± 1.2% in the fibronectin, respectively. BPH tissues presented a significant increase of fibronectin in prostatic periurethral region in the transitional zone that may cause lengthening of the prostatic urethra.
Assuntos
Fibronectinas/análise , Próstata/química , Hiperplasia Prostática/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores/análise , Estudos de Casos e Controles , Humanos , Imuno-Histoquímica , Masculino , Próstata/patologia , Hiperplasia Prostática/patologia , Regulação para Cima , Adulto JovemRESUMO
Moxifloxacin is reported to have increased distribution into the prostate compared with older fluoroquinolones such as norfloxacin and ciprofloxacin, being able to reach tissue-to-plasma concentration ratios greater than unity. However, most of these studies use tissue homogenates derived from biopsy samples, which can lead to overestimation of free concentrations as fluoroquinolones tend to accumulate in the intracellular space. The aim of this study was to investigate moxifloxacin pharmacokinetics in rat prostate interstitial fluid by microdialysis. Tissue pharmacokinetics was assessed by implanting a small microdialysis catheter in the prostate gland. Blood samples were simultaneously collected for assessing plasma pharmacokinetics. Analysis of plasma (N=154) and microdialysis (N=344) concentrations after a single intravenous dose of 6 or 12mg/kg moxifloxacin was conducted in the non-linear mixed-effect modelling software NONMEM v.6 as well by a non-compartmental approach. Moxifloxacin showed a significant tissue distribution in the prostate (AUCprostate,ISF/fu·AUCplasma=1.24±0.37), 59% higher than the value obtained for levofloxacin in a previous study. A three-compartment model with non-linear kinetics could adequately describe moxifloxacin pharmacokinetics in terms of curve fitting and precision in parameter estimation. The developed pharmacokinetic model indicates that passive diffusion and active transport are the mechanisms involved in moxifloxacin distribution to the prostate. These findings suggest that moxifloxacin could be a better alternative to levofloxacin for the treatment of chronic bacterial prostatitis owing to its enhanced tissue penetration and higher AUCtissue/MIC ratios, even though it is not yet approved by the US FDA for this indication.
Assuntos
Antibacterianos/farmacocinética , Fluoroquinolonas/farmacocinética , Microdiálise , Próstata/química , Administração Intravenosa , Animais , Antibacterianos/administração & dosagem , Antibacterianos/análise , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/análise , Masculino , Modelos Estatísticos , Moxifloxacina , Plasma/química , Ratos Wistar , Estados UnidosRESUMO
Objectives Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive agents in prostate cancer with a risk of high-grade disease. This study evaluated the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate cancer cells. Materials and Methods We retrospectively selected 21 patients who underwent TURP between March 2007 and February 2010 for previously confirmed BPH by prostate biopsy. They were grouped into control (group 1, n = 9) and 5ARI treatment (group 2, n = 12) before TURP. AR and HOXB13 expression in prostate tissue was evaluated by immunohistochemical staining. We tested the effect of 5ARI on the expression of AR, prostate specific antigen (PSA) and HOXB13 in LNCaP cells. Cells were assessed by Western blot analysis, MTT in vitro proliferation assay, and ELISA. Results: Group 2 showed stronger reactivity for AR and HOXB13 than those of the group 1. MTT assay showed death of LNCaP cells at 25uM of 5ARI. At the same time, ELISA assay for PSA showed that 5ARI inhibited secretion of PSA in LNCaP cells. Western blot analysis showed that 5ARI did not greatly alter AR expression but it stimulated the expression of HOXB13. Conclusions These results demonstrated that 5ARI influences AR and HOXB13 expression in both LNCaP cells and human prostate tissue. In order to use 5ARI in chemoprevention of prostate cancer, we still need to clarify the influence of 5ARI in ARs and oncogenic proteins and its regulation pathway. .
Assuntos
Idoso , Humanos , Masculino , /uso terapêutico , Proteínas de Homeodomínio/metabolismo , Hiperplasia Prostática/tratamento farmacológico , Receptores Androgênicos/metabolismo , Azasteroides/uso terapêutico , Western Blotting , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Antígeno Prostático Específico/sangue , Próstata/química , Próstata/efeitos dos fármacos , Hiperplasia Prostática/metabolismo , Estudos Retrospectivos , Fatores de Tempo , Células Tumorais Cultivadas , Fatores de Transcrição/análiseRESUMO
BACKGROUND: Prostate cancer (PC) is the second cause of death by cancer in men in Chile. Its behavior is so variable that it is necessary to search reliable prognostic markers. Vascular Endothelial Growth Factor (VEGF) is one of the most powerful pro-angiogenic factors. There is no agreement on its validity as a diagnostic or prognostic factor. AIM: To search for VEFG in prostatic tissue. MATERIAL AND METHODS: This study was performed in prostatectomy tissue coming from 41 patients with PC and 39 patients with benign prostatic hyperplasia (BPH). Specimens were studied using immunohistochemical staining for VEGF. The percentage of stained glandular cells per patient was calculated and associated with pathological diagnosis in cancer patients. RESULTS: PC biopsies had a mean of 82% of VEGF (+) stained cells, while BPH had only 1.6% (p < 0.01). No relationship was found between the percentage of staining and recurrence at one year of follow-up in the case of PC. CONCLUSIONS: These results would rule out VEGF as a prognostic factor in this series of patients.
Assuntos
Biomarcadores Tumorais/análise , Recidiva Local de Neoplasia/química , Próstata/química , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/química , Fator A de Crescimento do Endotélio Vascular/análise , Idoso , Biópsia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Próstata/patologia , Prostatectomia , Hiperplasia Prostática/patologia , Hiperplasia Prostática/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgiaRESUMO
Background: Prostate cancer (PC) is the second cause of death by cancer in men in Chile. Its behavior is so variable that it is necessary to search reliable prognostic markers. Vascular Endothelial Growth Factor (VEGF) is one of the most powerful pro-angiogenic factors. There is no agreement on its validity as a diagnostic or prognostic factor. Aim: To search for VEFG in prostatic tissue. Material and Methods: This study was performed in prostatectomy tissue coming from 41 patients with PC and 39 patients with benign prostatic hyperplasia (BPH). Specimens were studied using immunohistochemical staining for VEGF. The percentage of stained glandular cells per patient was calculated and associated with pathological diagnosis in cancer patients. Results: PC biopsies had a mean of 82% of VEGF (+) stained cells, while BPH had only 1.6% (p < 0.01). No relationship was found between the percentage of staining and recurrence at one year of follow-up in the case of PC. Conclusions: These results would rule out VEGF as a prognostic factor in this series of patients.
Assuntos
Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/química , Próstata/química , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/química , Biomarcadores Tumorais/análise , Fator A de Crescimento do Endotélio Vascular/análise , Biópsia , Imuno-Histoquímica , Valor Preditivo dos Testes , Próstata/patologia , Prostatectomia , Hiperplasia Prostática/patologia , Hiperplasia Prostática/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgiaRESUMO
OBJECTIVES: Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive agents in prostate cancer with a risk of high-grade disease. This study evaluated the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate cancer cells. MATERIALS AND METHODS: We retrospectively selected 21 patients who underwent TURP between March 2007 and February 2010 for previously confirmed BPH by prostate biopsy. They were grouped into control (group 1, n = 9) and 5ARI treatment (group 2, n = 12) before TURP. AR and HOXB13 expression in prostate tissue was evaluated by immunohistochemical staining. We tested the effect of 5ARI on the expression of AR, prostate specific antigen (PSA) and HOXB13 in LNCaP cells. Cells were assessed by Western blot analysis, MTT in vitro proliferation assay, and ELISA. RESULTS: Group 2 showed stronger reactivity for AR and HOXB13 than those of the group 1. MTT assay showed death of LNCaP cells at 25uM of 5ARI. At the same time, ELISA assay for PSA showed that 5ARI inhibited secretion of PSA in LNCaP cells. Western blot analysis showed that 5ARI did not greatly alter AR expression but it stimulated the expression of HOXB13. CONCLUSIONS: These results demonstrated that 5ARI influences AR and HOXB13 expression in both LNCaP cells and human prostate tissue. In order to use 5ARI in chemoprevention of prostate cancer, we still need to clarify the influence of 5ARI in ARs and oncogenic proteins and its regulation pathway.
Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Proteínas de Homeodomínio/metabolismo , Hiperplasia Prostática/tratamento farmacológico , Receptores Androgênicos/metabolismo , Idoso , Azasteroides/uso terapêutico , Western Blotting , Linhagem Celular Tumoral , Dutasterida , Ensaio de Imunoadsorção Enzimática , Humanos , Imuno-Histoquímica , Masculino , Próstata/química , Próstata/efeitos dos fármacos , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/metabolismo , Estudos Retrospectivos , Fatores de Tempo , Fatores de Transcrição/análise , Células Tumorais CultivadasRESUMO
Male accessory sexual glands arising in ovarian cystic teratoma are exceedingly rare. We report a 56-year-old female subjected to an ovariohysterectomy due to a left ovarian mass. The pathological study of the surgical piece revealed a tumor composed of different mature tissue elements and well defined nodules of benign prostatic tissue.
Assuntos
Cisto Dermoide/patologia , Neoplasias Ovarianas/patologia , Próstata/patologia , Teratoma/patologia , Fosfatase Ácida , Cisto Dermoide/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/química , Próstata/química , Antígeno Prostático Específico/análise , Proteínas Tirosina Fosfatases/análise , Teratoma/químicaRESUMO
Male accessory sexual glands arising in ovarian cystic teratoma are exceedingly rare. We report a 56-year-old female subjected to an ovariohysterectomy due to a left ovarian mass. The pathological study of the surgical piece revealed a tumor composed of different mature tissue elements and well defined nodules of benign prostatic tissue.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cisto Dermoide/patologia , Neoplasias Ovarianas/patologia , Próstata/patologia , Teratoma/patologia , Cisto Dermoide/química , Neoplasias Ovarianas/química , Antígeno Prostático Específico/análise , Próstata/química , Proteínas Tirosina Fosfatases/análise , Teratoma/químicaRESUMO
PURPOSE: Neuroendocrine differentiation is a hallmark of prostate cancer. The aim of our study was the detection of the parallel expression of neuroendocrine related markers using a prostate tissue microarray (TMA). MATERIALS AND METHODS: Our study was aimed at detecting the parallel expression of NeuroD1, Chromogranin-A (ChrA), Androgen Receptor (AR) and Ki-67 by immunohistochemistry on prostate cancer tissue microarray. The data was analyzed using SAS version 8.2 (SAS Inc, Cary, NC). The relationships between NeuroD1, ChrA and AR expressions and patients' characteristics were investigated by multivariate logistic regression analysis. Progression and Overall Survival (OS) distributions were calculated using Kaplan-Meier method. RESULTS: Tissue reactivity for NeuroD1, ChrA and AR concerned 73%, 49% and 77% of the available cases, respectively. Regarding overall survival, there were 87 deaths and 295 patients alive/censored (6 years of median follow-up). Seventy-seven disease progressions occurred at the median follow-up 5.4y. A significant correlation between NeuroD1, ChrA and AR expression was observed (p < 0.001 and p < 0.03, respectively). Additionally, ChrA was strongly associated in multivariate analysis to Gleason score and Ki67 expression (p < 0.009 and p < 0.0052, respectively). Survival analysis showed no association between markers neither for overall nor for cancer-specific survival. CONCLUSIONS: The results highlight that NeuroD1, Chromogranin-A and Androgen Receptor are strongly associated, however their expression does not correlate with overall survival or disease progression.