Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 196
Filtrar
1.
Pak J Pharm Sci ; 31(5(Special)): 2197-2201, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30463812

RESUMO

Endometriosis is a common disease among women of childbearing age, and it is the main cause of dysmenorrhea and infertility. This article analyzes the efficacy of mifepristone and gestrinone in the treatment of endometriosis. The results showed that the recurrence rate of mifepristone group and gestrinone group were 8.33% and 5%, respectively, which was significantly lower than 23.33% of the control group. Before and after treatment, LH, endocrine test results FSH PRL had no obvious change in mifepristone group and gestrinone group, while E2 decreased, as mifepristone group (141.7±31.2) pmol/L, gestrinone group (64.2±11.7) pmol/L. The incidence of adverse reactions and liver dysfunction in the mifepristone group were significantly lower than those the gestrinone group (P<0.05). Mifepristone and gestrinone can be used for endometriosis postoperative adjuvant treatment, is safe and effective, but using mifepristone has the lower rate of adverse reaction. In conclusion, mifepristone is a current research focus, its mechanism of action in the process of exploration, has broad prospects in the treatment of endometriosis, its long-term application security is paid more and more attention.


Assuntos
Endometriose/tratamento farmacológico , Gestrinone/uso terapêutico , Mifepristona/uso terapêutico , Adulto , Feminino , Humanos , Laparoscopia/métodos , Recidiva , Adulto Jovem
2.
Cochrane Database Syst Rev ; 7: CD009881, 2017 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-28742263

RESUMO

BACKGROUND: Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects in the endometrium, progesterone receptor modulators (PRMs) have been advocated for treatment of endometriosis. OBJECTIVES: To assess the effectiveness and safety of PRMs primarily in terms of pain relief as compared with other treatments or placebo or no treatment in women of reproductive age with endometriosis. SEARCH METHODS: We searched the following electronic databases, trial registers, and websites: the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register of Controlled Trials, the Central Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, clinicaltrials.gov, and the World Health Organization (WHO) platform, from inception to 28 November 2016. We handsearched reference lists of articles retrieved by the search. SELECTION CRITERIA: We included randomised controlled trials (RCTs) published in all languages that examined effects of PRMs for treatment of symptomatic endometriosis. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by the Cochrane Collaboration. Primary outcomes included measures of pain and side effects. MAIN RESULTS: We included 10 randomised controlled trials (RCTs) with 960 women. Two RCTs compared mifepristone versus placebo or versus a different dose of mifepristone, one RCT compared asoprisnil versus placebo, one compared ulipristal versus leuprolide acetate, and four compared gestrinone versus danazol, gonadotropin-releasing hormone (GnRH) analogues, or a different dose of gestrinone. The quality of evidence ranged from high to very low. The main limitations were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition in most studies), very serious imprecision (associated with low event rates and wide confidence intervals), and indirectness (outcome assessed in a select subgroup of participants). Mifepristone versus placebo One study made this comparison and reported rates of painful symptoms among women who reported symptoms at baseline.At three months, the mifepristone group had lower rates of dysmenorrhoea (odds ratio (OR) 0.08, 95% confidence interval (CI) 0.04 to 0.17; one RCT, n =352; moderate-quality evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. The mifepristone group also had lower rates of dyspareunia (OR 0.23, 95% CI 0.11 to 0.51; one RCT, n = 223; low-quality evidence). However, the mifepristone group had higher rates of side effects: Nearly 90% had amenorrhoea and 24% had hot flushes, although the placebo group reported only one event of each (1%) (high-quality evidence). Evidence was insufficient to show differences in rates of nausea, vomiting, or fatigue, if present. Mifepristone dose comparisons Two studies compared doses of mifepristone and found insufficient evidence to show differences between different doses in terms of effectiveness or safety, if present. However, subgroup analysis of comparisons between mifepristone and placebo suggest that the 2.5 mg dose may be less effective than 5 mg or 10 mg for treating dysmenorrhoea or dyspareunia. Gestrinone comparisons Ons study compared gestrinone with danazol, and another study compared gestrinone with leuprolin.Evidence was insufficient to show differences, if present, between gestrinone and danazol in rate of pain relief (those reporting no or mild pelvic pain) (OR 0.71, 95% CI 0.33 to 1.56; two RCTs, n = 230; very low-quality evidence), dysmenorrhoea (OR 0.72, 95% CI 0.39 to 1.33; two RCTs, n = 214; very low-quality evidence), or dyspareunia (OR 0.83, 95% CI 0.37 to 1.86; two RCTs, n = 222; very low-quality evidence). The gestrinone group had a higher rate of hirsutism (OR 2.63, 95% CI 1.60 to 4.32; two RCTs, n = 302; very low-quality evidence) and a lower rate of decreased breast size (OR 0.62, 95% CI 0.38 to 0.98; two RCTs, n = 302; low-quality evidence). Evidence was insufficient to show differences between groups, if present, in rate of hot flushes (OR 0.79, 95% CI 0.50 to 1.26; two RCTs, n = 302; very low-quality evidence) or acne (OR 1.45, 95% CI 0.90 to 2.33; two RCTs, n = 302; low-quality evidence).When researchers compared gestrinone versus leuprolin through measurements on the 1 to 3 verbal rating scale (lower score denotes benefit), the mean dysmenorrhoea score was higher in the gestrinone group (MD 0.35 points, 95% CI 0.12 to 0.58; one RCT, n = 55; low-quality evidence), but the mean dyspareunia score was lower in this group (MD 0.33 points, 95% CI 0.62 to 0.04; low-quality evidence). The gestrinone group had lower rates of amenorrhoea (OR 0.04, 95% CI 0.01 to 0.38; one RCT, n = 49; low-quality evidence) and hot flushes (OR 0.20, 95% CI 0.06 to 0.63; one study, n = 55; low quality evidence) but higher rates of spotting or bleeding (OR 22.92, 95% CI 2.64 to 198.66; one RCT, n = 49; low-quality evidence).Evidence was insufficient to show differences in effectiveness or safety between different doses of gestrinone, if present. Asoprisnil versus placebo One study (n = 130) made this comparison but did not report data suitable for analysis. Ulipristal versus leuprolide acetate One study (n = 38) made this comparison but did not report data suitable for analysis. AUTHORS' CONCLUSIONS: Among women with endometriosis, moderate-quality evidence shows that mifepristone relieves dysmenorrhoea, and low-quality evidence suggests that this agent relieves dyspareunia, although amenorrhoea and hot flushes are common side effects. Data on dosage were inconclusive, although they suggest that the 2.5 mg dose of mifepristone may be less effective than higher doses. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators.


Assuntos
Endometriose/tratamento farmacológico , Antagonistas de Hormônios/uso terapêutico , Mifepristona/uso terapêutico , Receptores de Progesterona/antagonistas & inibidores , Danazol/uso terapêutico , Dismenorreia/tratamento farmacológico , Dismenorreia/epidemiologia , Dispareunia/tratamento farmacológico , Dispareunia/epidemiologia , Estrenos/uso terapêutico , Feminino , Gestrinone/efeitos adversos , Gestrinone/uso terapêutico , Hormônio Liberador de Gonadotropina/análogos & derivados , Antagonistas de Hormônios/administração & dosagem , Antagonistas de Hormônios/efeitos adversos , Humanos , Leuprolida/efeitos adversos , Leuprolida/uso terapêutico , Mifepristona/administração & dosagem , Mifepristona/efeitos adversos , Norpregnadienos/uso terapêutico , Oximas/uso terapêutico , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Sci Rep ; 6: 27897, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-27302286

RESUMO

High-throughput in vitro screening experiments can be used to generate concentration-response data for large chemical libraries. It is often desirable to estimate the concentration needed to achieve a particular effect, or potency, for each chemical tested in an assay. Potency estimates can be used to directly compare chemical profiles and prioritize compounds for confirmation studies, or employed as input data for prediction modeling and association mapping. The concentration for half-maximal activity derived from the Hill equation model (i.e., AC50) is the most common potency measure applied in pharmacological research and toxicity testing. However, the AC50 parameter is subject to large uncertainty for many concentration-response relationships. In this study we introduce a new measure of potency based on a weighted Shannon entropy measure termed the weighted entropy score (WES). Our potency estimator (Point of Departure, PODWES) is defined as the concentration producing the maximum rate of change in weighted entropy along a concentration-response profile. This approach provides a new tool for potency estimation that does not depend on the assumption of monotonicity or any other pre-specified concentration-response relationship. PODWES estimates potency with greater precision and less bias compared to the conventional AC50 assessed across a range of simulated conditions.


Assuntos
Entropia , Ensaios de Triagem em Larga Escala/métodos , Modelos Teóricos , Bibliotecas de Moléculas Pequenas/farmacologia , Linhagem Celular , Simulação por Computador , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Estradiol/análogos & derivados , Estradiol/farmacologia , Gestrinone/farmacologia , Humanos , Fenóis/farmacologia , Receptores Estrogênicos/metabolismo , Reprodutibilidade dos Testes
4.
Clin Exp Obstet Gynecol ; 43(3): 350-3, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27328489

RESUMO

OBJECTIVE: To observe the effect of small-dose mifepristone conservative treatment and laparoscopic combined with mifepristone in the treatment of endometriosis. MATERIALS AND METHODS: Sixty-five endometriosis cases were given small-dose mifepristone conservative treatment and were assessed for the effect of this treatment; 92 cases were randomly divided into control group (taking gestrinone) and observation group (mifepristone), FSH, P, PRL and E2 levels were compared before and after treatment, and pregnancy investigation and each sex hormone level monitoring were followed-up at one year after drug withdrawal. RESULTS: Using mifepristone, FSH, P, E2, and LH levels all significantly changed six months after treatment and recovered 12 months after drug withdrawal; when comparing the pelvic symptoms, endometrial thickness showed that mifepristone was significantly effective (p < 0.01), and the pregnancy rate was 27.69%. Comparing the two groups, none of the total effective rate, pregnancy rate one year of follow-up, and recurrence rates were significantly different; hormone levels in the both groups were significantly decreased or increased (p < 0.05) after treatment. The two groups had no significant difference (p > 0.05), but 12 months after drug withdrawal, in the control group (not in the observation group), LH level was still significantly different (p < 0.05) compared pre-treatment. CONCLUSIONS: In the conservative treatment, mifepristone can safely improve the hormone levels, reduce the thickness of the endometrium, alleviate symptoms. With laparoscopic minimally invasive combined drug therapy, mifepristone has a significant effect, with a more followed-up pregnancy rate, less recurrence, and no drug accumulation side-effects, hence it is worthy of clinical application.


Assuntos
Endometriose/terapia , Antagonistas de Hormônios/uso terapêutico , Mifepristona/uso terapêutico , Adulto , Terapia Combinada , Dismenorreia/etiologia , Dispareunia/etiologia , Endometriose/sangue , Endometriose/complicações , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Gestrinone/uso terapêutico , Procedimentos Cirúrgicos em Ginecologia , Humanos , Laparoscopia , Hormônio Luteinizante/sangue , Dor Pélvica/etiologia , Gravidez , Progesterona/sangue , Progestinas/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
5.
Zhonghua Fu Chan Ke Za Zhi ; 51(2): 98-102, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-26917477

RESUMO

OBJECTIVE: To investigate the incidence, influencing factors and intervention of gestrinone-related abnormal uterine bleeding at different dosage of gestrinone in the clinical treatment. METHODS: This was a multicenter, randomized, control study of 195 Chinese women with endometriosis or adenomyosis from June 2011 to November 2013. The subjects were randomized into three groups with oral administration of gestrinone, 2.5 mg dose at one time; twice a week group: 67 cases with oral administration twice a week last three months; double dose first month group: 67 cases with oral administration triple times a week at first month, then twice a week for two months; three times a week group: 61 cases with oral administration three times a week last three months. The improvement of the abnormal uterine bleeding, the changes in estrogen, liver function and blood coagulation were evaluated. At the same time, B-ultrasound examination evaluation were performed. RESULTS: (1) Three months later, the incidence of abnormal uterine bleeding in twice a week group was 30% (20/67), in double dose first month group and three times a week group were 7%(5/67) and 16% (10/61) respectively, there were significant difference between three groups (P<0.05). The incidence in double dose first month group was the most lower. (2) Univariate analysis showed that the dosage and ovarian size were the significant factors for abnormal uterine bleeding (OR=0.461,P= 0.003;OR=0.303,P=0.016); logistic regression analysis demonstrated that the risk of abnormal uterine bleeding in double dose first month group was the lowest when compared with twice a week group and three times a week group, the risk in twice a week group was 5-fold higher than that in double dose first month group (OR=0.211,P=0.011). The incidence of abnormal uterine bleeding in participants with abnormal ovarian volume results from ovarian cyst or ovarian surgery was significantly lower than those with normal ovarian volume (OR=0.304,P=0.018). (3) After the treatment of three months, there were no significant difference in alanine transaminase level between the groups (P>0.05). The body mass index significantly increased in three group (P<0.05), but there were no significant differences between the groups (P>0.05). As for blood coagulation, there were also no significant differences between the groups (P>0.05). CONCLUSIONS: Double dose of gestrinone in the first month could significantly decrease the incidence of gestrinone-related abnormal uterine bleeding. It is a more optimied dosage of gestrinone and without severe side effects. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, registration number: ChiCTR-TRC-12002327.


Assuntos
Anticoncepcionais Orais/efeitos adversos , Gestrinone/efeitos adversos , Hemorragia Uterina/induzido quimicamente , Adenomiose , China/epidemiologia , Anticoncepcionais Orais/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Gestrinone/administração & dosagem , Humanos , Incidência , Cistos Ovarianos , Hemorragia Uterina/epidemiologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-26796059

RESUMO

Uterine leiomyomas, or fibroids, are the most common benign tumor in reproductive aged women. Affected women may remain asymptomatic or may report symptoms related to abnormal uterine bleeding, infertility, or pelvic pain and pressure. Depending on a patient's symptomatology and reproductive plans, treatment options include expectant management, medical management (hormonal and non-hormonal), or surgical management (myomectomy or hysterectomy). In those wishing to defer surgical management, non-hormonal therapies such as non-steroidal anti-inflammatory drugs and tranexamic acid have been shown to decrease menstrual blood loss. In patients with more symptomatic leiomyomas, hormonal therapies such as gonadotropin-releasing hormone agonists and selective progesterone receptor modulators are effective at reducing leiomyoma volume, uterine size, and menstrual blood loss. This manuscript will detail the available and emerging hormonal and non-hormonal treatments for symptomatic uterine leiomyomas.


Assuntos
Anticoncepcionais Femininos/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Leiomioma/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Antifibrinolíticos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Cabergolina , Colecalciferol/uso terapêutico , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Orais Hormonais/uso terapêutico , Anticoncepcionais Orais Sintéticos/uso terapêutico , Danazol/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Ergolinas/uso terapêutico , Estrenos/uso terapêutico , Antagonistas de Estrogênios/uso terapêutico , Feminino , Gestrinone/uso terapêutico , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Humanos , Dispositivos Intrauterinos Medicados , Levanogestrel/administração & dosagem , Mifepristona/uso terapêutico , Norpregnadienos/uso terapêutico , Oximas/uso terapêutico , Planejamento de Assistência ao Paciente , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Somatostatina/análogos & derivados , Ácido Tranexâmico/uso terapêutico , Vitaminas/uso terapêutico
7.
Zhongguo Zhong Yao Za Zhi ; 41(18): 3478-3482, 2016 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-28925135

RESUMO

To study the effect of Tripterygium wilfordii glycosides and gestrinone on endometriosis and serum cytokine expression, 135 cases of endometriosis patients were divided into treatment group(n=69) and control group(n=68). The observation group was orally given with T. wilfordii glycosides, 20 mg, tid, for 4 weeks. Then, the dose decreased to 10 mg/time, tid. T. wilfordii glycosides combined with gestrinone capsule(2.5 mg) were given in the 1st and 4th day of a menstrual cycle. Later, the administration was fixed at two times every week. The course of treatment lasted for 3 months. The control group was treated with gestrinone capsule(according to the same intake method). The serum-related cytokine levels before and after treatment were determined, and the clinical efficacy was observed. The results showed the total effective rate of the observation group was 89.71%, which was obviously higher than that of the control group(74.63%), with statistically significant differences(P<0.05). After treatment, TDS showed varying degrees of decreases, with a better effect in the observation group (P<0.01). Before treatment, serum TGF-ß, IL-10 and IL-4 level had no significant difference. After treatment, all of these cytokines decreased, particularly for the observation decreased(P<0.01). Before and after treatment, serum IL-17 had no obvious difference between the two groups. This study suggested that the integrated traditional Chinese medicine and western medicine has an obvious clinical efficiency in endometriosis. Its mechanism may be related to the effective regulation of cytokines.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Endometriose/tratamento farmacológico , Gestrinone/uso terapêutico , Glicosídeos/uso terapêutico , Tripterygium/química , Citocinas/sangue , Feminino , Humanos
8.
Laterality ; 21(2): 100-17, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26292019

RESUMO

Non-human primates represent models to understand the evolution of handedness in humans. Despite several researches have been investigating non-human primates handedness, few studies examined the relationship between target position, hand preference and task complexity. This study aimed at investigating macaque handedness in relation to target laterality and tastiness, as well as task complexity. Seven pig-tailed macaques (Macaca nemestrina) were involved in three different "two alternative choice" tests: one low-level task and two high-level tasks (HLTs). During the first and the third tests macaques could select a preferred food and a non-preferred food, whereas by modifying the design of the second test, macaques were presented with no-difference alternative per trial. Furthermore, a simple-reaching test was administered to assess hand preference in a social context. Macaques showed hand preference at individual level both in simple and complex tasks, but not in the simple-reaching test. Moreover, target position seemed to affect hand preference in retrieving an object in the low-level task, but not in the HLT. Additionally, individual hand preference seemed to be affected from the tastiness of the item to be retrieved. The results suggest that both target laterality and individual motivation might influence hand preference of macaques, especially in simple tasks.


Assuntos
Comportamento de Escolha/fisiologia , Lateralidade Funcional/fisiologia , Desempenho Psicomotor/fisiologia , Animais , Comportamento Animal , Comportamento Alimentar , Feminino , Gestrinone , Masculino
9.
J Obstet Gynaecol Res ; 41(5): 712-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25420776

RESUMO

AIM: The aim of this study was to determine clinical performance of gestrinone combined with ultrasound-guided aspiration and ethanol injection in treating chocolate cyst of ovary. METHODS: Sixty-eight patients enrolled in this study were randomly divided into two groups: control group and combination treatment group. In the control group, 34 patients were treated with ultrasound-guided aspiration and ethanol injection. In the combination treatment group, 34 patients received gestrinone p.o. following ultrasound-guided aspiration and ethanol injection. RESULTS: The recurrence rate of chocolate cyst was 10-fold lower in the combination treatment group (2.94%, 1/34) than in the control group (29.4%, 10/34) at 12 months. The effective rate for reduction of chocolate cyst was significantly higher in the combination treatment group (94.12%, 32/34) than in the control group (64.71%, 22/34) (P = 0.009). CONCLUSION: Gestrinone combined with ultrasound-guided aspiration and ethanol injection therapy is an effective treatment for ovarian chocolate cyst with low recurrence rate.


Assuntos
Etanol/uso terapêutico , Gestrinone/uso terapêutico , Cistos Ovarianos/terapia , Paracentese , Progestinas/uso terapêutico , Adulto , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Cistos Ovarianos/tratamento farmacológico , Cistos Ovarianos/cirurgia , Recidiva , Resultado do Tratamento , Ultrassonografia de Intervenção , Adulto Jovem
10.
Zhonghua Fu Chan Ke Za Zhi ; 48(2): 113-7, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23544492

RESUMO

OBJECTIVE: To investigate clinicopathological features of abdominal wall endometriosis (AWE). METHODS: A retrospective study was conducted on 151 consecutive AWE patients undergoing treatment in Affiliated Obstetrics and Gynecology Hospital, Fudan University from January 2003 to December 2010. The period of following up was at range of 16 to 97 months. RESULTS: (1) The incidence of AWE was 1.96% (166/8469). All 151 AWE cases followed up had previous cesarean sections. The period between the previous cesarean section (CS) and the onset of symptoms of AWE was 24 months (3 - 192 months). However, the latency was not associated with the age at CS, incision site, gestational week at CS, duration of lactation, postpartum menstruation recovery, the choice of contraceptives and size of AWE (P > 0.05). The duration of disease, defined to be the time interval between the onset of symptoms and surgery, was 26 months (2 - 168 months), which was negatively correlated with the latent period (r = -0.267, P < 0.05) and was positively with size of AWE (patients with large-scar endometrioma with diameter of lesions ≥ 3 cm had longer disease duration than those with small-scar endometriomas < 3 cm, r = 0.326, P < 0.05). (2) The rate of pre-operational ultrasonography detection was 97.4% (147/151). The lesion size detected by pre-operative ultrasonography was significantly smaller than that measured intraoperatively by palpation (20 mm versus 35 mm, P < 0.05). Moreover, only 26.5% (40/151) of AWE patients were found to have deep infiltration by pre-operative ultrasonography. (3) All patients were managed by surgical treatment to completely excise lesions on the abdominal wall. Of all 34 patients (22.5%, 34/151) took medicine pre-operatively while 57 patients (37.7%, 57/151) taking medicine post-operatively. The rate of recurrence was 3.1% (3/96) of cases with lesions ≥ 3 cm, which was significantly lower than 17.8% (8/45) in cases with lesion < 3 cm (P < 0.05). (4) After surgery, the symptoms were found to be relieved in 93.4% (141/151) of patients. The recurrence rate was 7.8% (11/141) while the average recurrent time was (20 ± 16) months. CONCLUSION: Surgery is the main management on AWE. The risk factors associated with recurrence were size of lesion and postoperative medication.


Assuntos
Parede Abdominal/patologia , Endometriose/patologia , Endometriose/cirurgia , Dor Abdominal/etiologia , Parede Abdominal/cirurgia , Adulto , Cesárea , Endometriose/diagnóstico , Endometriose/tratamento farmacológico , Feminino , Gestrinone/uso terapêutico , Gosserrelina/uso terapêutico , Humanos , Histerectomia , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
11.
Biomed Pharmacother ; 66(8): 569-77, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23102719

RESUMO

The study was to investigate the effect of gestrinone on the growth of human uterine leiomyoma cells and on the levels and activity of p38, Src and estrogen receptor alpha (ERα). Human uterine leiomyoma cells were cultured and treated with dimethylsulfoxide (DMSO) or a gestrinone concentration gradient. Morphological changes were observed and apoptosis was evaluated. Levels of p38 and phosphorylated-p38 (pp38) were assayed by enzyme-linked immunosorbent assay (ELISA). Levels of ERα and Src were analyzed using real-time RT-PCR and Western blotting. The result showed that gestrinone significantly inhibited the growth of cultured human uterine leiomyoma cells in a concentration- and time-dependent manner, with a 50% inhibitory concentration (IC(50)) value and corresponding 95% confidence intervals (CI) of 43.67 (23.46∼81.32), 27.78 (12.51∼61.68) and 15.25 (7.17∼32.43) µmol/L at 20, 40 and 60h, respectively. Compared with control-treated leiomyoma cells, gestrinone significantly reduced both the expression of ERα (P<0.05) and the levels of phospho-Ser167-ERα (P<0.05). Gestrinone also markedly suppressed the level of phospho-Tyr416-Src (P<0.05). Moreover, gestrinone significantly increased the ratio of phospho-p38/p38 mitogen-activated protein kinase (MAPK) (P<0.05). However, no significant increase in apoptosis or cell cycle arrest was observed (P>0.05) in response to the tested concentrations of 0.1 to 3.0µmol/L. As a conclusion, gestrinone suppresses the proliferation of uterine leiomyoma cells mainly by regulating the activity of ERα/Src/p38 MAPK in a concentration-dependent manner at a low concentration of 0.1∼3.0µM, but not significantly regulating apoptosis. Gestrinone opposes the growth of uterine leiomyoma through multiple genes.


Assuntos
Proliferação de Células/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Gestrinone/farmacologia , Leiomioma/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Quinases da Família src/metabolismo , Apoptose/efeitos dos fármacos , Western Blotting , Proteína Tirosina Quinase CSK , Técnicas de Cultura de Células , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Receptor alfa de Estrogênio/genética , Feminino , Gestrinone/administração & dosagem , Gestrinone/uso terapêutico , Humanos , Marcação In Situ das Extremidades Cortadas , Leiomioma/genética , Leiomioma/metabolismo , Leiomioma/ultraestrutura , Microscopia Eletrônica de Transmissão , Estrutura Molecular , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Tempo , Células Tumorais Cultivadas , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/ultraestrutura , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Quinases da Família src/genética
13.
Toxicol In Vitro ; 26(7): 1129-33, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22664790

RESUMO

For a long time, athletes have used androgenic anabolic steroids (AASs) in an inappropriate and veiled manner with the aim of improving exercise performance or for cosmetic purposes. Abuse of AASs triggers adverse effects such as hepatocarcinogenesis, heart attacks, and aggressive behavior. However, AAS-induced toxicity is not completely understood at the molecular level. In the present study, we showed, by performing a dioxin response element (DRE)-luciferase reporter gene assay, that tetrahydrogestrinone (THG), a popular and potent androgen receptor agonist, has dioxin-like effects. In addition, we showed that THG increased cytochrome P-450 1A1 (CYP1A1) mRNA and protein levels, and enzyme activity. The gene encoding CYP1A1 is involved in phase 1 xenobiotic metabolism and a target gene of the aryl hydrocarbon receptor (AhR). Using the AhR antagonist CH-223191, we also examined whether the effects of THG on DRE activation depended on AhR. Our results suggest that synthetic anabolic steroids may have dioxin-like side effects that can disturb endocrine systems and may cause other side effects including cancer through AhR.


Assuntos
Citocromo P-450 CYP1A1 , Dioxinas/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Gestrinone/análogos & derivados , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Elementos de Resposta/efeitos dos fármacos , Compostos Azo/farmacologia , Citocromo P-450 CYP1A1/biossíntese , Citocromo P-450 CYP1A1/genética , Genes Reporter/efeitos dos fármacos , Genes Reporter/genética , Gestrinone/farmacologia , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/enzimologia , Humanos , Luciferases/metabolismo , Pirazóis/farmacologia , RNA Mensageiro/metabolismo , Receptores de Hidrocarboneto Arílico/agonistas , Receptores de Hidrocarboneto Arílico/antagonistas & inibidores , Elementos de Resposta/genética
14.
Cochrane Database Syst Rev ; (5): CD006568, 2012 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-22592712

RESUMO

BACKGROUND: Endometriosis is characterized by the presence of tissue that is morphologically and biologically similar to normal endometrium in locations outside the uterus. Surgical and hormonal treatment of endometriosis have unpleasant side effects and high rates of relapse. In China, treatment of endometriosis using Chinese herbal medicine (CHM) is routine and considerable research into the role of CHM in alleviating pain, promoting fertility, and preventing relapse has taken place.This review is an update of a previous review published in the Cochrane Database of Systematic Reviews 2009, issue No 3. OBJECTIVES: To review the effectiveness and safety of CHM in alleviating endometriosis-related pain and infertility. SEARCH METHODS: We searched the Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library) and the following English language electronic databases (from their inception to 31/10/2011): MEDLINE, EMBASE, AMED, CINAHL, and NLH.We also searched Chinese language electronic databases: Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Sci & Tech Journals (VIP), Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS), and Chinese Medical Current Contents (CMCC). SELECTION CRITERIA: Randomised controlled trials (RCTs) involving CHM versus placebo, biomedical treatment, another CHM intervention; or CHM plus biomedical treatment versus biomedical treatment were selected. Only trials with confirmed randomisation procedures and laparoscopic diagnosis of endometriosis were included. DATA COLLECTION AND ANALYSIS: Risk of bias assessment, and data extraction and analysis were performed independently by three review authors. Data were combined for meta-analysis using relative risk (RR) for dichotomous data. A fixed-effect statistical model was used, where appropriate. Data not suitable for meta-analysis were presented as descriptive data. MAIN RESULTS: Two Chinese RCTs involving 158 women were included in this review. Both these trials described adequate methodology. Neither trial compared CHM with placebo treatment.There was no evidence of a significant difference in rates of symptomatic relief between CHM and gestrinone administered subsequent to laparoscopic surgery (95.65% versus 93.87%; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.93 to 1.12, one RCT). The intention-to-treat analysis also showed no significant difference between the groups (RR 1.04, 95% CI 0.91 to 1.18). There was no significant difference between the CHM and gestrinone groups with regard to the total pregnancy rate (69.6% versus 59.1%; RR 1.18, 95% CI 0.87 to 1.59, one RCT).CHM administered orally and then in conjunction with a herbal enema resulted in a greater proportion of women obtaining symptomatic relief than with danazol (RR 5.06, 95% CI 1.28 to 20.05; RR 5.63, 95% CI 1.47 to 21.54, respectively). Overall, 100% of women in all the groups showed some improvement in their symptoms.Oral plus enema administration of CHM showed a greater reduction in average dysmenorrhoea pain scores than did danazol (mean difference (MD) -2.90, 95% CI -4.55 to -1.25; P < 0.01). Combined oral and enema administration of CHM also showed a greater improvement measured as the disappearance or shrinkage of adnexal masses than with danazol (RR 1.70, 95% CI 1.04 to 2.78). For lumbosacral pain, rectal discomfort, or vaginal nodules tenderness, there was no significant difference between CHM and danazol. AUTHORS' CONCLUSIONS: Post-surgical administration of CHM may have comparable benefits to gestrinone but with fewer side effects. Oral CHM may have a better overall treatment effect than danazol; it may be more effective in relieving dysmenorrhoea and shrinking adnexal masses when used in conjunction with a CHM enema. However, more rigorous research is required to accurately assess the potential role of CHM in treating endometriosis.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Endometriose/tratamento farmacológico , Dor Pélvica/tratamento farmacológico , Danazol/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Dismenorreia/tratamento farmacológico , Endometriose/complicações , Enema/métodos , Antagonistas de Estrogênios/uso terapêutico , Feminino , Gestrinone/uso terapêutico , Humanos , Dor Pélvica/etiologia , Progestinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Cochrane Database Syst Rev ; (3): CD002122, 2012 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-22419284

RESUMO

BACKGROUND: Endometriosis is a chronic inflammatory condition defined by the presence of glands and stroma outside the uterine cavity. It occurs in 7% to 10% of all women of reproductive age and may present as pain or infertility. The pelvic pain may be in the form of dysmenorrhoea, dyspareunia or pelvic pain. Initially a combination of estrogens and progestagens was used to create a pseudopregnancy and alleviate the symptoms associated with endometriosis. Progestagens alone or anti-progestagens have been considered as alternatives because they are inexpensive and may have a better side effect profile than other choices. OBJECTIVES: To determine the effectiveness of both the progestagens and anti-progestagens in the treatment of painful symptoms ascribed to the diagnosis of endometriosis. SEARCH METHODS: We used the search strategy of the Menstrual Disorders and Subfertility Group to identify all publications which described or might have described randomised controlled trials (RCTs) of any progestagen or any anti-progestagen in the treatment of symptomatic endometriosis. We updated the review in 2011. SELECTION CRITERIA: We considered only RCTs which compared the use of progestagens and anti-progestagens with other interventions, placebo or no treatment for the alleviation of symptomatic endometriosis. DATA COLLECTION AND ANALYSIS: We have added six new studies, bringing the total of included studies to 13 in the update of this review. The six newly included studies evaluated progestagens (comparisons with placebo, danazol, oral or subdermal contraceptive, oral contraceptive pill and danazol, gonadotrophin-releasing hormone (GnRH) analogue and other drugs). The remaining studies compared the anti-progestagen gestrinone with danazol, GnRH analogues or itself. MAIN RESULTS: The progestagen medroxyprogesterone acetate (100 mg daily) appeared to be more effective at reducing all symptoms up to 12 months of follow-up (MD -0.70, 95% CI -8.61 to -5.39; P < 0.00001) compared with placebo. There was evidence of significantly more cases of acne (six versus one) and oedema (11 versus one) in the medroxyprogesterone acetate group compared with placebo. There was no evidence of a difference in objective efficacy between dydrogesterone and placebo.There was no evidence of a benefit with depot administration of progestagens versus other treatments (low dose oral contraceptive or leuprolide acetate) for reduced symptoms. The depot progestagen group experienced significantly more adverse effects.There was no overall evidence of a benefit of oral progestagens over other medical treatment at six months of follow-up for self-reported efficacy. Amenorrhoea and bleeding were more frequently reported in the progestagen group compared with other treatment groups.There was no evidence of a benefit of anti-progestagens (gestrinone) compared with danazol. GnRH analogue (leuprorelin) was found to significantly improve dysmenorrhoea compared with gestrinone (MD 0.82, 95% CI 0.15 to 1.49; P = 0.02) although it was also associated with increased hot flushes (OR 0.20, 95% CI 0.06 to -0.63; P = 0.006). AUTHORS' CONCLUSIONS: There is only limited evidence to support the use of progestagens and anti-progestagens for pain associated with endometriosis.


Assuntos
Endometriose/tratamento farmacológico , Dor Pélvica/tratamento farmacológico , Congêneres da Progesterona/uso terapêutico , Progestinas/antagonistas & inibidores , Danazol/uso terapêutico , Didrogesterona/uso terapêutico , Endometriose/complicações , Feminino , Gestrinone/uso terapêutico , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Leuprolida/uso terapêutico , Acetato de Medroxiprogesterona/uso terapêutico , Dor Pélvica/etiologia
16.
Biosens Bioelectron ; 26(12): 4842-7, 2011 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-21733669

RESUMO

In a previous work we introduced the term Bio-Photonic Sensing Cells (BICELLs), referred to periodic networks of nano-pillar suitable for biosensing when are vertically interrogated. In this article, we demonstrate the biosensing capabilities of a type of micrometric size BICELLs made of SU-8 nano-pillars fabricated over transparent substrates. We verify the biochips functionality comparing the theoretical simulations with the experimental results when are optically interrogated in transmission. We also demonstrate a sensitivity enhancement by reducing the pitch among nano-pillars from 800 to 700 nm. Thus, the Limit of Detection achievable in these types of BICELLs is in the order of 64 pg/mL for 700 nm in pitch among nano-pillars in comparison with 292 pg/mL for 800 nm in pitch when are interrogated by Fourier Transform Visible and Infrared Spectrometry. The experiments exhibited a good reproducibility with a relative standard deviation of 0.29% measured within 8 days for a specific concentration. Finally, BICELLs functionality was tested in real conditions with unpurified rabbit serum for detecting anti-gestrinone antibodies, demonstrating the high performance of this type of BICELLs to detect specific antibodies having immobilized the suitable bioreceptors onto the sensing surface.


Assuntos
Anticorpos/sangue , Técnicas Biossensoriais/instrumentação , Gestrinone/imunologia , Nanoestruturas/química , Animais , Anticorpos/imunologia , Desenho de Equipamento , Imunoensaio/instrumentação , Limite de Detecção , Óptica e Fotônica/instrumentação , Polímeros/química , Coelhos
18.
Talanta ; 82(4): 1581-7, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20801376

RESUMO

Gestrinone is a synthetic steroid hormone with anti-estrogenic and anti-progesterone properties. It is used to treat endometriosis, shrink uterine fibroids and reduce menorrhagia; besides, it has been investigated for use as contraceptive. Also, due to its anabolic effects, it has been included in the banned list of performance enhanced drugs in sport. Polyclonal antibodies raised against bovine serum albumin coupled to gestrinone 3-carboxymethyloxime (3OCMO-G) were used to develop two highly sensitive and specific enzyme-linked immunosorbent assays for gestrinone. One of them, based on direct format, shows a detection limit (LD) of 0.09+/-0.03 ng L(-1). The second assay, hapten-protein coating format, can detect until (LD) 0.14+/-0.05 ng L(-1). Both immunoassays were also highly specific, showing negligible or no cross-reactivity to other anabolic steroids. The developed ELISAs detected lower amounts of gestrinone than those determined by the reference chromatographic HPLC/MS/MS methods. The direct format was applied to quantify this steroid in spiked human urine without sample pre-treatment, with recovery values between 76 and 122%.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Gestrinone/análise , Cromatografia Líquida de Alta Pressão , Reações Cruzadas , Humanos , Limite de Detecção , Espectrometria de Massas em Tandem
19.
Obstet Gynecol ; 115(4): 740-4, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20308833

RESUMO

OBJECTIVE: To compare the efficacy of gestrinone with that of mifepristone for emergency contraception. METHODS: A randomized double-blind trial was conducted in five family-planning clinics in China. We randomly assigned 998 healthy women with regular menstrual cycles and negative urine pregnancy tests who were requesting emergency contraception up to 72 hours after unprotected coitus to receive single-dose 10 mg gestrinone (n=499) or 10 mg mifepristone (n=499). We monitored them to 7 days after the expected first day of their next menstrual period. The study was powered to detect a 5% failure rate between the two regimens. RESULTS: The treatment groups did not differ significantly; posttreatment pregnancy rates were 2.4% in the gestrinone group compared with 1.8% in the mifepristone group (P=.51). The majority of women menstruated the first day of expected menses, and groups did not differ regarding side effects. CONCLUSION: The effectiveness of 10 mg gestrinone is not significantly different from 10 mg mifepristone as an emergency contraceptive method. CLINICAL TRIAL REGISTRATION: ISRCTN Register, isrctn.org, ISRCTN87842530. LEVEL OF EVIDENCE: I.


Assuntos
Abortivos Esteroides/administração & dosagem , Anticoncepção Pós-Coito , Gestrinone/administração & dosagem , Mifepristona/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Gravidez , Resultado do Tratamento
20.
Rapid Commun Mass Spectrom ; 23(15): 2329-37, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19575408

RESUMO

Glucocorticosteroids are a restricted class of substances and appear on the 'in-competition' prohibited list of the World Anti-Doping Agency (WADA). Analysis of glucocorticosteroids is complicated since they show significant phase 1 and 2 metabolism in the human body and are excreted into urine in concentrations in the microg/L range. Full scan, high-resolution time-of-flight mass spectrometry analysis generates information on all ionisable components in urine, including known and unknown metabolites of steroids and even designer modifications of anabolic steroids. However, evaluation of the data obtained can be difficult and time-consuming because of the need to differentiate between endogenous components and compounds of interest. MetaboLynx, a spectral and chromatographic search program, was modified for the determination of in silico predicted metabolites of glucocorticosteroids and designer modifications of anabolic steroids in human urine. Spiked urine samples were successfully screened for known components in a targeted approach and for unknown species in a non-targeted approach using data filtering to limit potential false-positives. A simplified combined approach of targeted and untargeted screening was used for the detection of metabolites and designer modifications of existing compounds. This approach proved successful and showed its strength in the detection of tetrahydrogestrinone (THG), a designer modification of gestrinone. THG was positively detected in a spiked urine sample and correctly identified as a twofold hydrogenation of gestrinone. The developed screening method can easily be adapted to specific needs and it is envisaged that a similar approach would be amendable to the discovery of metabolites or designer modifications of other compounds of interest.


Assuntos
Cromatografia Líquida/métodos , Glucocorticoides/metabolismo , Glucocorticoides/urina , Espectrometria de Massas/métodos , Software , Detecção do Abuso de Substâncias/métodos , Gestrinone/análogos & derivados , Gestrinone/metabolismo , Gestrinone/urina , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA