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Objective @# To investigate the effect of miR-135a-5p on the expression levels of insulin-like factor 3 (INSL3) and testosterone in the testicular tissues of flutamide-induced cryptorchidism mouse.@*Methods @# A model of flutamide-induced cryptorchidism in mouse was constructed,and the experiment was divided into normal control group,flutamide group,flutamide + miR-135a-5p knockdown group and flutamide + miR-135a-5p overexpression group. RT-qPCR was used to detect the expression levels of miR-135a-5p and INSL3 mRNA.Western blot was em- ployed to assess the protein expression level of INSL3.ELISA was performed to measure the expression level of tes- tosterone. @*Results @#The expression levels of miR-135a-5p,INSL3 mRNA and protein and testosterone were significantly down-regulated in the testis of cryptorchid mice by flutamide (P<0. 05) .Knockdown of miR-135a-5p could downregulate the expression of INSL3 mRNA,INSL3 protein and testosterone (P <0. 01 ) ,while overexpression of miR-135a-5p had the opposite result.@*Conclusion @#miR-135a-5p decreased in flutamide-induced cryptorchidism mouse testicular tissues,and overexpression of miR-135a-5p could restore the expression levels of INSL3 and testosterone.
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AIM: To investigate the effect of flutamide on mitochondrial biogenesis and the regulating effect of anoxidative pathway Nrf2 on it. METHODS: Human hepatocyte HepG2 cells were treated with flutamide (0-50 μmol/L) for 24 h, then mtDNA copy number and protein expression of mitochondrial biogenesis were detected by RT-PCR and WB. The effects of ERK1/2 and the role of Nrf2 pathway in mitochondrial biogenesis were further observed by gene knockdown and protein activation/inhibition methods. RESULTS: Flutamide interfered mitochondrial biogenesis concentration-dependently, the mtDNA copy number, ERK1/2 and PGC-1α proteins increased with the dose. ERK1/2 inhibition and activation regulated flutamide-induced mtDNA copy number and PGC-1α expression, and inhibition of Nrf2 pathway also affected flutamide-induced mtDNA copy number and expression of PGC-1α, as well as ERK1/2 expression. CONCLUSION: Flutamide affects mitochondrial biogenesis, and the antioxidant pathway Nrf2 may be involved in the regulation of flutamine-induced mitochondrial biogenesis by regulating ERK1/2.
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Aim: The efficacy and therapeutic benefit of flutamide (FLU) can be clinically limited by the occurrence of hepatotoxicity which may progress to liver failure. This study, therefore, evaluated the protective effect of coenzyme Q 10 (COQ 10) against FLU-induced liver toxicity in albino rats.Objectives: The objectives of this study were to explore and grade the severity of IA in relation to academic performance among medical undergraduates.Materials and Methods: Forty-five adult albino rats of average weight 200–250 g were randomized into groups and treated intraperitoneally with COQ 10; 50 mg/kg + FLU 200 mg/kg, COQ 10; 100 mg/kg + FLU 200 mg/kg and COQ 10; and 200 mg/kg + FLU 200 daily for 7 days. On the 8th day, rats were sacrificed, serum was extracted from blood and liver was excised and evaluated for aspartate aminotransferase (AST), alanine aminotransferase(ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), total bilirubin (TB), and conjugated bilirubin (CB). Liver was evaluated for oxidative stress markers and pathologic changes.Results: Serum and liver AST, ALT, ALP, AST, GGT, LDH, TB, and CB levels were significantly (P < 0.001) increased in FLU-treated rats when compared to placebo control. Liver superoxide dismutase, catalase, glutathione, and glutathione peroxidase were decreased, whereas malondialdehyde levels were increased significantly (P < 0.001) in FLU-treated rats when compared to placebo control. The liver of FLU-treated rats showed hepatocyte necrosis. However, FLU-induced liver toxicity was significantly abrogated in a dose-dependent manner in COQ 10; 50 mg/kg (P < 0.05), COQ 10; 100 mg/kg (P < 0.01); and COQ 10; 200 mg/kg (P < 0.001) pre-treated rats when compared to FLU-treated rats.Conclusions: This study showed that COQ 10 abrogates FLU-induced hepatotoxicity in albino rats in a dose- dependent manner. It may have clinical application in hepatotoxicity associated with FLU.
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Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen (NSAA) is still widely used in treating metastatic castration-resistant prostate cancer (mCRPC), especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate (Abi) remains uncertain. In the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA (from bicalutamide to flutamide) before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan-Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival (PSA-PFS, 5.5 vs 5.6 months, P = 0.967), radiographic progression-free survival (rPFS, 12.8 vs 13.4 months, P = 0.508), overall survival (OS, not reached vs 30.6 months, P = 0.606), or PSA-response rate (71.4% [15/21] vs 60.6% [40/66], P = 0.370). This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors' decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.
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Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen (NSAA) is still widely used in treating metastatic castration-resistant prostate cancer (mCRPC), especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate (Abi) remains uncertain. In the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA (from bicalutamide to flutamide) before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan-Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival (PSA-PFS, 5.5 vs 5.6 months, P = 0.967), radiographic progression-free survival (rPFS, 12.8 vs 13.4 months, P = 0.508), overall survival (OS, not reached vs 30.6 months, P = 0.606), or PSA-response rate (71.4% [15/21] vs 60.6% [40/66], P = 0.370). This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors' decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.
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Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Acetato de Abiraterona/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Anilidas/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Intervalo Livre de Doença , Flutamida/uso terapêutico , Estimativa de Kaplan-Meier , Nitrilas/uso terapêutico , Drogas Antiandrogênicas não Esteroides/uso terapêutico , Antígeno Prostático Específico/análise , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Estudos Retrospectivos , Análise de Sobrevida , Compostos de Tosil/uso terapêutico , Resultado do TratamentoRESUMO
In the current work, a sustained drug delivery system of flutamide (FLT) was developed using Poly(D,L-lactide-co-glycolide) (PLGA) decorated bypoly(ethylene glycol) (PEG) grafted prazosin (PLGA-PEG-Praz) as a targeting moiety. In a multi-step reaction, PLGA was linked to PEG and prazosin. The structure of the synthesized polymers was confirmed by FTIR and 1H-NMR. Flutamide-loaded nanoparticles were prepared by quasi-emulsion solvent diffusion technique. The nanoparticles were evaluated for size, zeta potential, polydispersity index, drug crystallinity, loading efficiency, and release properties. Also, the physicochemical properties of the nanoparticles were analyzed using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry, and Powder X-Ray Diffractometry (XRD). The particle size of nanoparticles was ranged between 191 and 249 nm. Loading efficiency of nanoparticles was about 43%-69%. Results showed a steady release rate for nanoparticles compared to that of a pure drug powder. SEM characterization confirmed that particles were in nanosize range. DSC and XRPD results verified a decrease in drug crystallinity in the prepared formulations. In conclusion, the results of this study showed that PLGA-PEG-Praz nanoparticles could be a good choice to improve the physicochemical properties of the drug and these formulations can increase Flutamide efficacy.
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Prazosina/análise , Nanopartículas , Flutamida/uso terapêutico , Neoplasias da Próstata/fisiopatologia , Espectroscopia de Infravermelho com Transformada de Fourier/instrumentaçãoRESUMO
Aim: This study was carried out to determine the effects of Cissus populnea and Panax ginseng on flutamide-induced testicular toxicities in pre-pubertal rats. Place and Duration of Study: Department of Anatomy, College of Medicine of the University of Lagos, Lagos – Nigeria, between May and December 2010. Methodology: 20 male immature (25 days old) Wistar rats were used. They were randomly divided into 4 groups; 1 control and 3 treatment groups. Group A served as control, group B was administered flutamide and Cissus populnea, group C was administered flutamide and Panax ginseng and group D was administered flutamide alone. Body weight and testicular weights were measured. Hormonal assay for testosterone, FSH and LH were done using Enzyme-Linked Immunosorbent Assay (ELISA). Histopathology of the testis was also investigated. Result: There were no statistically significant differences in serum testosterone levels in all three treatment groups when compared with the control group. There was a significant increase in the serum LH level in group D when compared with the control group (p<0.05). Serum FSH level in group B showed a significant increase when compared with the control group (p<0.05). The histological evidences of testis in group D showed a reduction in lining cells of the seminiferous tubules; however, in the other three treatment groups they were similar to the control group. Conclusion: The results suggest that Cissus populnea and Panax ginseng ameliorates the adverse effects of flutamide on the testis.
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Este trabalho de revisão apresenta o tratamento hormonal da acne baseado em evidências. O trabalho resume a clínica, a classificação, a fisiopatologia e a etiologia da acne. A avaliação de estudos selecionados mostrou que o tratamento hormonal da acne deve ser complementado por tratamento cosmiátrico, e não está indicado para gestantes ou mulheres com planos de engravidar. A primeira escolha para esse tratamento são os contraceptivos hormonais orais, pois são efetivos e seguros para tratamento da acne e também para anticoncepção. Após tempo estabelecido, se o resultado for insatisfatório, outro medicamento, como acetato de ciproterona ou espironolactona, deve ser adicionado. A finasterida é o medicamento indicado para acne de origem idiopática, e a flutamida apresenta efeitos colaterais significativos, não constituindo indicação segura até o momento.
This review shows the hormonal treatment of acne. The review summarizes the clinical aspects, classification, physiopathology and etiology of the acne. The evaluation of selected papers showed that hormonal treatment of acne with hormones has to be complemented by esthetics treatment and is not prescribed for pregnant women or those who want to get pregnant. The first choice of treatment is the hormonal oral contraceptive one, because it is effective and safe for treatment of acne and also for contraception. After an established period with unsatisfactory results, other medicines, such as ciproterone acetate or spironolactone, can be added. The finasteride is prescribed for idiopathic acne and flutamide has many relevant side effects and is also not safe.
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Humanos , Masculino , Feminino , Acetato de Ciproterona/análogos & derivados , Acetato de Ciproterona/uso terapêutico , Acne Vulgar/etiologia , Acne Vulgar/fisiopatologia , Acne Vulgar/tratamento farmacológico , Anticoncepcionais Orais Hormonais/administração & dosagem , Anticoncepcionais Orais Hormonais/uso terapêutico , Espironolactona/uso terapêutico , Finasterida/uso terapêutico , Flutamida/uso terapêutico , Cosméticos , Medicina Baseada em Evidências , Hiperandrogenismo/tratamento farmacológico , Avaliação de Resultados em Cuidados de SaúdeRESUMO
A revisão de estudos baseados em evidências mostra o melhor tratamento hormonal para o hirsutismo. Inicialmente, resumiu-se a fisiologia do pelo, caracterizou-se o hirsutismo, suas variantes e suas causas. Revelou-se que o tratamento hormonal do hirsutismo deve ser complementado pelo tratamento cosmético e não deve ser indicado para mulheres grávidas ou que desejam engravidar. A primeira opção é o contraceptivo hormonal oral, seguro para contracepção e eficaz para tratamento do hirsutismo. Após tempo estipulado, não ocorrendo resposta satisfatória, associar acetato de ciproterona ou espironolactona. A finasterida é indicada para hirsutismo idiopático e a flutamida, devido aos efeitos colaterais, ainda não é opção segura
An evidence-based review shows the best hormonal treatment of hirsutism. This paper summarized the physiology of the hair, characterized the hirsutism, its variants and etiologies. The study revealed that hormonal treatment of hirsutism has to be complemented by esthetic treatment, and it is not recommended for pregnant women or for those who want to get pregnant. The first option is hormonal oral contraceptive, which is safe for contraception and effective for treatment of hirsutism. After a established period of treatment, if good results do not occur, the association of cyproterone or spironolactone is recomended. Finasteride is the treatment of idiopathic hirsutism, and flutamide is not a safe option due to its side effects
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Humanos , Feminino , Acetato de Ciproterona/administração & dosagem , Acetato de Ciproterona/uso terapêutico , Anticoncepcionais Orais/uso terapêutico , Cabelo/crescimento & desenvolvimento , Espironolactona/administração & dosagem , Espironolactona/uso terapêutico , Finasterida/efeitos adversos , Flutamida/efeitos adversos , Hirsutismo/tratamento farmacológico , Hirsutismo/terapia , Técnicas Cosméticas , Cabelo/metabolismoRESUMO
Objective To compare the efficacy,toxicitis and side-effects of Casodex and Flutamide in the hormonal therapy of advanced prostate cancer patients.Methods One hundred and thirty-six advanced prostate cancer patients were treated with with hormonal therapy.The patients were divided into 3 groups,of which 52 patients (group A) used LHRHa and Casodex as intermittent hormonal therapy;60 patients(group B) used LHRHa and Flutamide as intermittent hormonal therapy;24 patients(group C) were treated with surgical castration only.The difference of clinical symptoms,serum PSA,disease progression risk,survival rate,toxicitis and side-effects of 3 groups were compared.Results The relief rates of group A and B were 80.8% (42/52)and 81.7% (49/60) respectively,higher than 70.8% (17/24) of group C.The mean serum PSA of group A and B decreased from 133.3 ng/ml(17.9-982.8 ng/ml) to 15.8 ng/ml(0.02-28.9 ng/ml),142.6 ng/ml (20.2-1001.0 ng/ml)to 16.1 ng/ml(0.07-53.8 ng/ml),respectively,both better than that of group C,which decreased from 142.3 ng/ml (27.1-988.0 ng/ml) to 27.6 ng/ml(6.0-62.1 ng/ml).The mean chemical recurrence rates of group A and B were 34.7% (18/52) and 36.7% (22/60),respectively,lower than 58.3% (14/24) of group C.The mean chemical recurrence time of group A and B was 22(5-52)months and 22(6-65)months,respectively,longer than 11(5-54)months of group C.The mortality rates of group A and B were 26.9% (14/52) and 31.7% (19/60),respectively,lower than 66.7%(16/24) of group C.88.5% (46/52)of group A were treated continuously,while group B had 66.7% (40/60).The side-effects rate of group A was lower than group B.Conclusions Both Cadosex and Flutamide are effective for prostate cancer,and decrease the disease progression risk.Casodex is more effective and safer as for the treatment of prostate cancer compared to Flutamide.
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AIM: To explore the effect of Buddleia flavonoids drug-containing plasma and androgen receptor(AR) blocker on the expression of STAT1 phosphoprotein.METHODS: In vitro lacrimal gland epithelial cells were cultivated with H2O2 to establish the dry eye apoptosis state. Blank plasma group, Buddleia officinalis plasma total flavonoids interfere with drug-containing group, and the intervention group of testosterone propionate were set. The expressions of STAT1 phosphoprotein of each group were observed by Western blot and AR blocker flutamide was used to explore the intended androgen effect of Buddleia flavonoids.RESULTS: After the intervention of drug-containing plasma, the expression of STAT1 Phosphoprotein in Buddleja officinalis drug-containing plasma intervention group(0.353±0.494) and testosterone propionate intervention group(0.502±0.036) were enhanced and the differences between the two groups were significant (P<0.01). After using the AR blocker in all groups, the expression of STAT1 phosphoprotein in each group (0.268±0.061,0.283±0.106,0.213±0.071) had no difference.CONCLUSION: Buddleja officinalis drug-containing plasma total flavonoids can promote the expression of STAT1 phosphorylation.
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La flutamida es un antiandrógeno no esteroideo, utilizado como terapia a largo plazo para el cáncer de próstata. Entre los efectos secundarios se incluye toxicidad hepática, la cual es muy rara vez reportada. Se presenta el caso de un adulto de 71 años con cáncer de próstata que desarrolla episodio de hepatitis colestásica durante tratamiento con flutamida. Luego de suspender la flutamida el paciente recupera progresivamente su función hepática, pero presenta recurrencia más severa al reiniciar la droga.No se justifica el reinicio del tratamiento luego de un primer episodio de hepatitis tóxica y es necesario tener en cuenta la toxicidad hepática del fármaco, cuando se decide indicarlo como tratamiento.
Flutamide is a nonsteroidal antiandrogen, used like therapy a long term for the prostate cancer. Between the indirects effects the hepatic toxicity is included, which is very rarely reported. The case of an adult of 71 years old with prostate cancer appears that develops episode of cholestatic hepatitis during treatment with flutamide. After to suspend flutamide the patient it recovers progressively his hepatic function, but he presented a recurrence more severely upon reintroduction of the drug.The resumption of the treatment after a first episode of toxic hepatitis is not justified and is necessary to consider the hepatic toxicity of the drug, when it is decided to indicate it like treatment.
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Humanos , Masculino , Idoso , Flutamida , Neoplasias da PróstataRESUMO
The general aim of this paper was to characterize some changes induced by androgen receptors blockage in the epithelial cells of the mouse epididymis. The antiandrogen flutamide was injected (10 mg/Kg b.w.) to adult male mice which were sacrificed 24h. and 72h. after. Controls injected with the vehicle (corn oil) were sacrificed at the same intervals. Cryosections were made of the epididymides and examined by the TUNEL method for quantification of apoptosis and also using immunocytochemistry to visualize the expression of the stress protein HSP70. The highest indexes of apoptosis were observed in the caput epididymis after 72 h. and were of 7.40 cells/1000 in contrast to controls (0.21 cells/1000). HSP70 appeared particularly increased in the caput and cauda epididymis after 72 h. treatment. Results indicated that the blockage of androgen receptors induces apoptosis and a HSP70 expression in the principal epithelial cells of the mouse epididymis, and that these changes occur in a region-specific fashion.
Este trabajo estudia los cambios inducidos por el bloqueador de receptores de andrógeno flutamida en el epitelio del epidídimo del ratón. Varios machos adultos fueron inyectados con flutamida (1Omg/Kg.b.w.) y se sacrificaron a las 24 y 72horas. Otros machos, que sirvieron de controles fueron inyectados sólo con el vehículo empleado para las inyecciones (aceite de maíz) y se sacrificaron a intervalos similares. Los epidídimos tratados y controles fueron examinados mediante el método TÚNEL para cuantificar la apoptosis y mediante procedimientos inmunocitoquímicos para localizar la proteína de stress HSP70. El índice apoptótico más alto fue observado en la cabeza del epidídimo después de 72 horas de tratamiento. HSP70 se observó también a las 72 horas en la cabeza y en la cauda epididimaria. Los resultados indican que el bloqueo de los receptores de andrógenos induce apoptosis y expresión de HSP70 en las células principales del epitelio epididimario, y que estos cambios ocurren afectando a regiones específicas del epidídimo.
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Masculino , Adulto , Animais , Camundongos , Antagonistas de Androgênios , Epididimo/anatomia & histologia , Epididimo/crescimento & desenvolvimento , Epididimo , Flutamida/administração & dosagem , Flutamida/toxicidade , Apoptose , Células Epiteliais , Homeostase , Microscopia de Tunelamento/métodos , /efeitos adversos , /metabolismoRESUMO
with flutamide has a syn-ergistic action in inhibiting the proliferation of LNCaP.
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PURPOSE: Flutamide (4-nitro-3-t-trifluoromethyl-isobutyranilide) is an androgen-receptor antagonist with typical antiandrogenic effect, used to treat androgen-dependent disorders such as prostate cancer. However, some reports noted that flutamide has direct effects to neuronal cells. It has been shown to retard the development of electrical kindling in rats. METHODS: We used the chemoconvulsant 4-aminopyridine (4-AP) and picrotoxin (PTX) in the in vitro hippocampal slice model to determine of flutamide for the suppression of epileptiform discharges. Extracellular field potential recordings were obtained from the CA3 pyramidal layer of hippocampus. RESULTS: The concentration of 30 and 100 micrometer flutamide suppressed the whole mean number of epileptiform discharges to 57.8% and 66.8% each compared with the 4-AP only slices. In 100 micrometer PTX, 10 and 30 micrometer flutamide suppressed the whole mean number of epileptiform discharges to 56.6% and 82.5% each. Intermixed with flumazenil, the anticonvulsant effect of flutamide was decreased. CONCLUSIONS: Flutamide suppressed epileptiform discharges induced by 4-AP and PTX in vitro seizure model. It suggests that flutamide influence to anti-epileptic activity by benzodiazepine site of the GABAA receptor.
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4-Aminopiridina , Benzodiazepinas , Flumazenil , Flutamida , Neurônios , Picrotoxina , Neoplasias da Próstata , ConvulsõesRESUMO
Detrimental effects of tributyltin (TBT) chloride on the reproductive system were investigated in pubertal male rats. Sixty Sprague-Dawley rats aged with 35 days were assigned to six different groups; negative control receiving vehicle, positive control receiving methyltestosterone (10 mg/kg B.W.), TBT chloride (5 mg/kg B.W., 10 mg/kg B.W., and 20 mg/kg B.W.), and a combination of TBT chloride (10 mg/kg B.W.) and flutamide (10 mg/kg B.W). The animals were treated with test compounds by oral gavage daily for 10 days and sacrificed on the next day of the final treatment. The treatment with TBT chloride at the doses of 10 and 20 mg/kg B.W. significantly decreased seminal vesicle weights, compared to the negative control. The combined treatment of TBT chloride and flutamide caused a significant decrease in accessory sex organ weights, compared to the control and TBT chloride treatments. The treatment with TBT chloride or in the combination with flutamide increased detached debris and sloughed cells in the tubules of epididymis and narrowed seminal vesicles. In addition, the combined treatment with TBT chloride and flutamide caused a noticeable increase in serum androgen level, compared to the negative control.These results suggest that TBT chloride exposed during pubertal period cause partial reproductive disorders in male rats.
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Animais , Masculino , Ratos , Peso Corporal , Epididimo/efeitos dos fármacos , Flutamida/farmacologia , Genitália Masculina/efeitos dos fármacos , Metiltestosterona/farmacologia , Tamanho do Órgão , Próstata/efeitos dos fármacos , Ratos Sprague-Dawley , Glândulas Seminais/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Testículo/efeitos dos fármacos , Compostos de Trialquitina/farmacologiaRESUMO
Objective To study the toxic effect of flutamide (Flu) on testis with DNA chip. Methods Flu was injected subcutaneously at doses of 6.25 mg?kg-1 ?d-1 to 25 F0 rats from gestation day (GD) 12 to 17, and the 25 rats of control group received same doses of normal saline. All 50 pregnant SD rats were sacrificed on GD 20.The cDNA were extracted respectively from fetal testis, then reversely transcribed to cDNA and labeled with cy5 and cy3 fluorescence. Subsequently, cDNA probes were hybridized to the Mouse40S cDNA microarray and fluorescence signals were analyzed. Testosterone level was determined by enzyme-linked immunosorbent assay (ELISA). Results Compared with control,a total of 31 identified gene was found to be expressed differently, including 14 down-regulated and 17 up-regulated. Among them, 5 down-regulated and 10 up-regulated genes were unknown in Genbank. ELISA indicated that testosterone levels were decreased in Flu toxic group. Conclusion Flu treatment to F0 pregnant rats can damage apparently to the reproductive development of embryonic period male SD rats. The obtained differential genes may provide reference for the molecular mechanism of reproductive development.
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0.05).In groups A and B,the intraoperative blood loss was(94.4?51.6)ml and(155.8?84.3)ml;the 4% mannitol solution used for intraoperative irrigation was(18.4?6.2)L and(25.4?8.8)L;the operative time was(65.0?16.4)min and((86.8?)25.0)min;the time for postoperative bladder infusion was(46.5?9.1)h and(57.8?17.4)h;the infused saline volume was(19.2?4.2)L and(26.7?10.2)L;the degree of satisfaction of the surgeons with the TURP field was 75.0%(36/48) and 41.9%(26/62);the cases who needed to increase the perfusion pressure during TURP accounted for 22.9%(11/48) and 45.2%(28/62);the blood transfusion rates were 6.2%(3/48) and 22.6%(14/62);and the incidence rates of secondary prostatic bleeding were(10.4)%(5/48) and 25.8%(16/62),respectively.The differences in all these parameters were statistically significant between the 2 groups(P
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PURPOSE: We attempted to investigate whether calcitonin gene-related peptide binding to receptors in the gubernaculum is different between normal and flutamide-treated rats or pups and whether calcitonin gene-related peptide(CGRP) binding is androgen dependent. MATERIALS AND METHODS: Timed pregnant Sprague Dawley rats were injected with flutamide or vehicle alone once daily on gestational days 15-19. Weight, anogenital distance and distance from testicle to symphisis pubis of pups of gestational day 20 and rats of neonatal day 1 and 7 were measured. Gubernacular sections from rats of neonatal day 7 were incubated with [125I]human CGRP with various concentrations of unlabeled hCGRP, and those from pups of gestational day 20 and rats of neonatal day 1 were incubated only with [125I]human CGRP. After exposure of gubernacular sections to imaging plate (BAS 2500), the images from the plate were quantified by computerized densitometry (TINA). RESULTS: Weight and anogenital distance of flutamide-treated pups or neonatal rats were significantly smaller and shorter than those of normal pups or neonatal rats (P< 0.01). Though the distance from testicle to symphisis pubis was not significantly different between normal and flutamide-treated pups or neonatal 1 day rats, that of flutamide-treated neonatal 7 day rats was significantly longer than that of normal neonatal 7 day rats (P< 0.01). The total binding counts of [125I]human CGRP on gubernacular sections of normal pups, neonatal 1 day rats and neonatal 7 day rats were 56.3 +/- 24.74, 68.2 +/- 24.90, 78.4 +/- 17.25 (dpm/mg polymer), respectively, and those of flutamide- treated pups, neonatal 1 day rats and neonatal 7 day rats were 43.7 +/- 12.54, 35.1 +/- 8.25, 57.5 +/- 16.27, respectively. There were significant differences between normal and flutamide-treated neonatal 1 day and 7 day rats (P< 0.01). The binding in normal rats was consistently increased from gestational day 20 to neonatal day 7, and it showed weak correlation (r = 0.398, P< 0.05). The binding analysis showed that concentrations of CGRP receptors were 20.0+/- 4.78 amol/mg polymer, 13.3 +/- 3.87 amol/mg polymer for normal and flutamide treated neonatal 7 day rats, respectively, and there was significant difference between normal and flutamide-treated rats (P< 0.01). However there was no significant difference in the dissociation constant between 2 models. The images from the plate in flutamide-treated neonatal 7 day rats looked smaller than those in normal 7 day rats. CONCLUSIONS: These results suggest that the inguinoscrotal descent of testicle occurs after the gubernacular eversion, CGRP binding in the gubernaculum is androgen dependent, and androgen may not influence CGRP release from genitofemoral nerve because of down regulation of CGRP receptor by antiandrogen. However, the role of CGRP in testicular descent is still obscure and the mechanism of down regulation of CGRP receptor by antiandrogen needs further investigation
Assuntos
Animais , Masculino , Ratos , Peptídeo Relacionado com Gene de Calcitonina , Calcitonina , Criptorquidismo , Densitometria , Regulação para Baixo , Flutamida , Polímeros , Ratos Sprague-Dawley , Receptores de Peptídeo Relacionado com o Gene de Calcitonina , TestículoRESUMO
PURPOSE: The purpose of this study was to evaluate the feasibility of using intermittent androgen deprivation(IAD) in patients with prostate cancer. MATERIALS AND METHODS: We reviewed the medical records of 29 patients treated with IAD for prostate cancer. Androgen deprivation with goserelin and flutamide was continued for at least 4 months after serum prostate specific antigen(PSA) became undetectable or a nadir level was reached. Medication was then discontinued until serum PSA reached a predetermined level. This cycle of treatment was repeated until there was evidence of androgen independence. RESULTS: Twenty-one patients completed the on-treatment during cycle 1, with a median time to PSA nadir of 3 months. Nine patients completed cycle 1 with a median time of off-treatment of 11 months(38% of a treatment cycle). Eight patients continued the off-treatment during cycle 1 for 1+ to 8+ months. During cycle 2, 3 patients achieved a PSA nadir in a median time of 3.5 months. While off treatment, most patients reported reduction of symptoms associated with androgen suppression. CONCLUSIONS: IAD is a feasible alternative for continuous androgen deprivation for treatment of prostate cancer. It also results in the reducion of toxicity, cost of treatment, and possibly a delay in tumor progression.