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2.
AAPS PharmSciTech ; 21(3): 80, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31975311

RESUMO

Bromocriptine mesylate (BCM), a dopaminergic agonist administered orally, exhibits retarded bioavailability owing to poor absorption and extreme first-pass metabolism. The objective of the current study was to develop, characterize, and statistically optimize BCM nanoemulsion (BCM-NE) loaded into a gel (BCM-NE gel) to evaluate its potential for improved permeation of BCM through the transdermal route, thereby improving its pharmacokinetic profile. BCM-NE was prepared by o/w spontaneous emulsification method and the effects of different formulation variables on the critical attributes of NE like globule size were investigated by implementing factorial design. The optimized formulation exhibited a mean globule size of 160 ± 6.5 nm, zeta potential of - 20.4 ± 1.23 mV, and drug content of 99.45 ± 1.9%. Ex vivo permeation studies across rat skin exhibited a significant enhancement in permeation, i.e., enhancement ratio (ER) of ~ 7.4 and 5.86 for BCM-NE and BCM-NE gel, respectively, when compared with aqueous BCM suspension gel. In vivo pharmacokinetic studies performed in rats demonstrated a higher and prolonged drug release of BCM from BCM-NE gel when compared to oral aqueous BCM suspension. The AUC0-t for BCM-NE gel and BCM suspension was found to be 562.54 ± 77.55 and 204.96 ± 51.93 ng/ml h, respectively. The relative bioavailability (%F) of BCM was shown to be enhanced 274% by BCM-NE gel. Histopathological studies demonstrated the safety and biocompatibility of the developed system. All the above results proved that the BCM-NE gel could be a superior and patient-compliant alternative to oral delivery in the management of PD.


Assuntos
Bromocriptina/administração & dosagem , Administração Cutânea , Animais , Bromocriptina/química , Bromocriptina/farmacocinética , Emulsões/administração & dosagem , Géis/química , Masculino , Nanotecnologia , Ratos , Ratos Wistar , Pele/metabolismo
3.
Horm Metab Res ; 52(1): 58-66, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31537024

RESUMO

Early weaning (EW) is a risk factor for metabolic syndrome. Male rats that were precociously weaned present neonatal malnutrition and, in adulthood, developed overweight, accumulation of body fat, dyslipidemia, changes in glycemic homeostasis, hyperleptinemia, and increase of vitamin D. As metabolic profile of early-weaned females is not known, we investigated the endocrine-metabolic parameters in adolescence and adult female rats of 2 different EW models. Wistar lactating rats and pups from both sexes were separated into 3 groups: non-pharmacological EW (NPEW), dams were involved with a bandage interrupting suckling in the last 3 days of lactation; pharmacological EW (PEW), dams were bromocriptine-treated (0.5 mg/twice a day via intraperitoneal injection) for 3 days before weaning; and control, dams whose pups ate milk throughout lactation. At 21 days-old, NPEW and PEW females had lower body weight. At 180 days-old, NPEW and PEW females showed higher feed efficiency, weight gain, body fat percentage, and greater accumulation of gonadal and retroperitoneal fat depots associated with adipocyte hypertrophy. NPEW females also showed hyperphagia. Only NPEW females presented hyperleptinemia. Plasma thyroid hormones and vitamin D were unchanged among EW females. Regarding sex hormones, at 45 days-old, no change was found in EW females, while at 180 days-old, PEW females had hypoestrogenemia. EW increases the risk for obesity in female rats in adulthood, as already demonstrated for males, although through distinct mechanisms involving some hormones.


Assuntos
Adiposidade , Hormônios/sangue , Desmame , Adiposidade/efeitos dos fármacos , Fatores Etários , Animais , Glicemia/metabolismo , Bromocriptina/administração & dosagem , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/metabolismo , Feminino , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Masculino , Ratos , Ratos Wistar , Hormônios Tireóideos/sangue , Vitamina D/sangue
4.
Iran Biomed J ; 24(1): 24-9, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31454860

RESUMO

Background: In recent years, nanotechnology with modern advances in the macromolecular design of nano-carriers has proved to be helpful in the development of drugs delivery systems. This research represents a novel co-administration of nano-vehicles, known as liposomes. Liposomes efficiently encapsulate curcumin and bromocriptine (BR) in a polymer structure, which results in enhanced aqueous solubility of the mentioned hydrophobic agents and higher bioavailability of the drugs. Methods: Preparation of curcumin and BR liposomes were carried out by the thin film method, and the amounts of purified drug and its release were analyzed. After dose determination, the human lung cancer cells (QU-DB) were exposed to BR and curcumin liposomes for 12, 24, and 48 h. Then the viability and apoptosis assays were carried out by using tetrazolium dye and flow cytometry technique, respectively. Results: In this research, in vitro anti-cancer effects of former nano-formulations on lung cancer cells was confirmed, and no cytotoxicity effects of these nano-preparations were observed in the normal cells (HFLF-PI5). Discussion: Our findings suggest the nano-liposomal drugs as effective anti-cancer agents; however, additional clinical examinations are required.


Assuntos
Apoptose , Bromocriptina/administração & dosagem , Bromocriptina/uso terapêutico , Curcumina/administração & dosagem , Curcumina/uso terapêutico , Sistemas de Liberação de Medicamentos , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Apoptose/efeitos dos fármacos , Bromocriptina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Liberação Controlada de Fármacos , Humanos , Lipossomos , Neoplasias Pulmonares/patologia , Tamanho da Partícula
5.
Rehabilitacion (Madr) ; 53(3): 155-161, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31370942

RESUMO

INTRODUCTION: The aim of this study was to assess the results and adverse effects of bromocriptine in patients with traumatic brain injury-vegetative state (TBI-VS) or traumatic brain injury-minimally conscious state (TBI-MCS). METHODS: We conducted a retrospective review of 10 patients, six with TBI-VS and four with TBI-MCS. All patients received bromocriptine at a starting dose of 2.5mg twice daily. Bromocriptine was titrated up to 7.5 or 12.5mg twice daily according to response and was maintained for at least 4 weeks. Various assessment scales were used in the following stages: before bromocriptine administration, at 4 weeks post bromocriptine prescription, and at hospital discharge. The assessment scales used were the Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale, Glasgow Coma Scale, Barthel Scale, and Marshall Scale. RESULTS: Of the 10 patients, four with TBI-MCS and four with TBI-VS achieved a score of 23 points at discharge in the CRS-R, thus emerging from VS or MCS and regaining functional status. There were only two patients who emerged from VS but remained in MCS (8 to 11 and 5 to 10 points in CRS-R). CONCLUSIONS: Considering the poor prognosis for recovery in these patients, bromocriptine use has a positive risk-benefit ratio at a dosage of at least 7.5mg twice daily for 4 weeks.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Bromocriptina/uso terapêutico , Fármacos do Sistema Nervoso Central/uso terapêutico , Transtornos da Consciência/tratamento farmacológico , Adolescente , Adulto , Bromocriptina/administração & dosagem , Fármacos do Sistema Nervoso Central/administração & dosagem , Coma Pós-Traumatismo da Cabeça/tratamento farmacológico , Esquema de Medicação , Humanos , Pessoa de Meia-Idade , Estado Vegetativo Persistente/tratamento farmacológico , Estudos Retrospectivos , Medição de Risco , Índices de Gravidade do Trauma , Adulto Jovem
6.
Pan Afr Med J ; 32: 50, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31143355

RESUMO

We here report the case of a 29-year old gravida 2, para 2 patient with no particular past medical history. Symptoms evolved over 2 months and were marked by bilateral breast growth impairing her daily activities. Clinical examination showed hypertrophied breasts and bilateral breast ulcers. She had a history of 28-weeks amenorrhea. Anatomopathological examination of ulcers showed fleshy bud-like tissue. The patient had high levels of prolactin (1345 µUI/ml). The levels of FSH and LH were normal. The patient underwent bromocriptine therapy without success. Patient's evolution was marked by decrease in size and regression in skin ulcers six months after vaginal birth. Gestational gigantomastia is a breast hypertrophy characterized by a breast volume exceeding 1500 cm3 . Its cause is unknown. Radical treatment is based on bilateral mastectomy.


Assuntos
Mama/anormalidades , Hipertrofia/patologia , Complicações na Gravidez/patologia , Prolactina/sangue , Adulto , Mama/patologia , Bromocriptina/administração & dosagem , Feminino , Humanos , Gravidez
7.
Acta Obstet Gynecol Scand ; 98(10): 1341-1350, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31025313

RESUMO

INTRODUCTION: Adenomyosis is a benign uterine disease where endometrial glands and stroma are found within the myometrium surrounded by an area of hypertrophic myometrium. Symptomatology includes heavy menstrual bleeding and pelvic pain. The pathogenesis of adenomyosis is not known; however, animal models have shown increased uterine concentration of prolactin as a risk factor. Prolactin acts as a smooth muscle cell mitogen. If prolactin is central to adenomyosis pathogenesis, reducing uterine prolactin could be a possible medical treatment option. In this pilot study, we aim to evaluate the effect of bromocriptine, a prolactin inhibitor, on menstrual bleeding and pain in women with adenomyosis. MATERIAL AND METHODS: 23 women with diffuse adenomyosis were enrolled from a university hospital in Sweden and a tertiary care center in the USA. Nineteen patients completed 6 months of treatment with vaginal bromocriptine at a dose of 5 mg daily. Participants completed validated measures at baseline, 3 and 6 months of treatment, and at 9 months (3 months after cessation of bromocriptine). Validated measures utilized included Pictorial Blood Loss Assessment Chart (PBLAC), Aberdeen Menorrhagia Clinical Outcomes Questionnaire (AMCOQ), Visual Analog Scale for pain (VAS), McGill Pain Questionnaire (MPQ), Endometriosis Health Profile (EHP-30), Female Sexual Function Index (FSFI) and the Fibroid Symptom Quality of Life (UFS-QOL) symptom severity and health-related quality of life (HRQL) subscores. Scores were compared between baseline and 9 months using the Wilcoxon signed rank test. RESULTS: Mean age of participants was 44.8 years. About 77.8% reported PBLAC scores >250 and 68.4% reported moderate to severe pain at baseline. Compared with baseline, women had lower 9-month scores (median [interquartile range] for all) on PBLAC (baseline 349 [292-645] vs 9-month 233 [149-515], P = 0.003), VAS (5.0 [4-8.3] vs 2.5 [0-4.5], P < 0.001), EHP Core Pain (15.9 [9.1-50.0] vs 3.4 [2.3-34.1], P = 0.029), EHP Core Self-image (41.7 [16.7-58.3] vs 25 [0-5], P = 0.048) and Symptom Severity Score (60 [44-72] vs 44 [25-56], P < 0.001) and higher HRQL scores (57 [37-63] vs 72 [51-85], P < 0.001) following bromocriptine treatment. Other EHP core parameters and FSFI were not significantly different. CONCLUSIONS: Significant improvement in menstrual bleeding, pain and quality of life after vaginal bromocriptine treatment suggests a novel therapeutic agent for adenomyosis.


Assuntos
Adenomiose/tratamento farmacológico , Bromocriptina/administração & dosagem , Dismenorreia/tratamento farmacológico , Antagonistas de Hormônios/administração & dosagem , Manejo da Dor/métodos , Qualidade de Vida , Administração Intravaginal , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Medição da Dor , Projetos Piloto , Suécia , Estados Unidos
8.
Cereb Cortex ; 29(3): 1162-1173, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29415163

RESUMO

Dopamine D2 receptors (D2Rs) contribute to the inverted U-shaped relationship between dopamine signaling and prefrontal function. Genetic networks from post-mortem human brain revealed 84 partner genes co-expressed with DRD2. Moreover, eight functional single nucleotide polymorphisms combined into a polygenic co-expression index (PCI) predicted co-expression of this DRD2 network and were associated with prefrontal function in humans. Here, we investigated the non-linear association of the PCI with behavioral and Working Memory (WM) related brain response to pharmacological D2Rs stimulation. Fifty healthy volunteers took part in a double-blind, placebo-controlled, functional MRI (fMRI) study with bromocriptine and performed the N-Back task. The PCI by drug interaction was significant on both WM behavioral scores (P = 0.046) and related prefrontal activity (all corrected P < 0.05) using a polynomial PCI model. Non-linear responses under placebo were reversed by bromocriptine administration. fMRI results on placebo were replicated in an independent sample of 50 participants who did not receive drug administration (P = 0.034). These results match earlier evidence in non-human primates and confirm the physiological relevance of this DRD2 co-expression network. Results show that in healthy subjects, different alleles evaluated as an ensemble are associated with non-linear prefrontal responses. Therefore, brain response to a dopaminergic drug may depend on a complex system of allelic patterns associated with DRD2 co-expression.


Assuntos
Memória de Curto Prazo/fisiologia , Herança Multifatorial , Córtex Pré-Frontal/fisiologia , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/fisiologia , Adulto , Mapeamento Encefálico , Bromocriptina/administração & dosagem , Estudos Cross-Over , Agonistas de Dopamina/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Córtex Pré-Frontal/efeitos dos fármacos , Adulto Jovem
9.
Endocrinology ; 160(1): 193-204, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30462197

RESUMO

Previous studies have shown that bromocriptine mesylate (Bromo) lowers blood glucose levels in adults with type 2 diabetes mellitus; however, the mechanism of action of the antidiabetic effects of Bromo is unclear. As a dopamine receptor agonist, Bromo can alter brain dopamine activity affecting glucose control, but it also suppresses prolactin (Prl) secretion, and Prl levels modulate glucose homeostasis. Thus, the objective of the current study was to investigate whether Bromo improves insulin sensitivity via inhibition of Prl secretion. Male and female ob/ob animals (a mouse model of obesity and insulin resistance) were treated with Bromo and/or Prl. Bromo-treated ob/ob mice exhibited lower serum Prl concentration, improved glucose and insulin tolerance, and increased insulin sensitivity in the liver and skeletal muscle compared with vehicle-treated mice. Prl replacement in Bromo-treated mice normalized serum Prl concentration without inducing hyperprolactinemia. Importantly, Prl replacement partially reversed the improvements in glucose homeostasis caused by Bromo treatment. The effects of the Prl receptor antagonist G129R-hPrl on glucose homeostasis were also investigated. We found that central G129R-hPrl infusion increased insulin tolerance of male ob/ob mice. In summary, our findings indicate that part of Bromo effects on glucose homeostasis are associated with decrease in serum Prl levels. Because G129R-hPrl treatment also improved the insulin sensitivity of ob/ob mice, pharmacological compounds that inhibit Prl signaling may represent a promising therapeutic approach to control blood glucose levels in individuals with insulin resistance.


Assuntos
Bromocriptina/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Prolactina/metabolismo , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Obesos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo
10.
Am J Ther ; 26(4): e433-e440, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29746287

RESUMO

BACKGROUND: Elevated prolactin levels were found to be associated with impaired sexuality. STUDY QUESTION: The aim of the study was to compare the impact of bromocriptine and cabergoline on sexual functioning in both genders. STUDY DESIGN: The study enrolled 39 young women and 18 young men receiving bromocriptine treatment. In 19 women and 8 men, because of poor tolerance, bromocriptine was replaced with cabergoline, whereas the remaining ones continued bromocriptine treatment. MEASURES AND OUTCOMES: Apart from measuring serum levels of prolactin and insulin sensitivity, at the beginning of the study and 16 weeks later, all included patients completed questionnaires evaluating female or male sexual functioning (Female Sexual Function Index; International Index of Erectile Function-15). RESULTS: Irrespective of the gender, posttreatment prolactin levels were lower in cabergoline-treated patients than in bromocriptine-treated patients. Baseline sexual functioning did not differ between patients well and poorly tolerating bromocriptine treatment. Neither in men nor in women receiving bromocriptine, posttreatment sexual functioning differed from baseline one. In both genders, cabergoline improved sexual desire. Moreover, in men, the drug improved erectile and orgasmic function, whereas in women, it improved sexual arousal. All these effects correlated with the impact of this drug on prolactin levels and on insulin sensitivity. CONCLUSIONS: Cabergoline is superior to bromocriptine in affecting male and female sexual functioning and should be preferred in hyperprolactinemic men and women with sexual dysfunction.


Assuntos
Bromocriptina/administração & dosagem , Cabergolina/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Hiperprolactinemia/tratamento farmacológico , Disfunções Sexuais Fisiológicas/prevenção & controle , Adulto , Feminino , Humanos , Hiperprolactinemia/sangue , Hiperprolactinemia/complicações , Masculino , Pessoa de Meia-Idade , Orgasmo/efeitos dos fármacos , Orgasmo/fisiologia , Ereção Peniana/efeitos dos fármacos , Ereção Peniana/fisiologia , Prolactina/sangue , Prolactina/fisiologia , Disfunções Sexuais Fisiológicas/sangue , Disfunções Sexuais Fisiológicas/etiologia , Resultado do Tratamento , Adulto Jovem
11.
Clin Res Cardiol ; 108(3): 290-297, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30121697

RESUMO

BACKGROUND: Right ventricular (RV) dysfunction predicts adverse outcome in peripartum cardiomyopathy (PPCM). We recently demonstrated beneficial effects associated with the prolactin release inhibitor bromocriptine at different doses when added to standard heart failure therapy in PPCM. Here, we evaluated for the first time the therapeutic potential of bromocriptine particularly in PPCM patients with RV involvement. METHODS: In this study, 40 patients with PPCM were included, of whom 24 patients had reduced RV ejection fraction (RVEF < 45%). We examined the effect of short-term (1W: bromocriptine, 2.5 mg, 7 days, n = 10) compared with long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for another 6 weeks, n = 14) in addition to guideline-based heart failure therapy in patients with an initial RVEF < 45% on the following outcomes: (1) change from baseline (Δ delta) in RVEF, (2) change from baseline in left ventricular EF (LVEF), and (3) rate of patients with full LV recovery (LVEF ≥ 50%) and (4) rate of patients with full RV recovery (RVEF ≥ 55%) at 6-month follow-up as assessed by cardiac magnetic resonance imaging. RESULTS: Reduced RVEF at initial presentation was associated with a lower rate of full cardiac recovery at 6-month follow-up (patients with RV dysfunction: 58% vs. patients with normal RV function: 81%; p = 0.027). RVEF increased from 38 ± 7 to 53 ± 11% with a delta-RVEF of + 15 ± 12% in the 1W group, and from 35 ± 9 to 58 ± 7% with a Δ RVEF of + 23 ± 10% in the 8W group (Δ RVEF 1W vs 8W: p = 0.118). LVEF increased from 25 ± 8 to 46 ± 12% with a Δ LVEF of + 21 ± 11% in the 1W group, and from 22 ± 6 to 49 ± 10% with a Δ LVEF of + 27 ± 9% in the 8W group (Δ LVEF 1W vs 8W: p = 0.211). Full LV recovery was present in 50% of the 1W group and in 64% of the 8W group (p = 0.678). Full RV recovery was observed in 40% of the 1W group and in 79% of the 8W group (p = 0.092). CONCLUSIONS: Despite overall worse outcome in patients with RV dysfunction at baseline, bromocriptine treatment in PPCM patients with RV involvement was associated with a high rate of full RV and LV recovery, although no significant differences were observed between the short-term and long-term bromocriptine treatment regime. These findings suggest that bromocriptine in addition to standard heart failure therapy may be also effective in PPCM patients with biventricular impairment.


Assuntos
Bromocriptina/administração & dosagem , Cardiomiopatias/tratamento farmacológico , Período Periparto , Complicações Cardiovasculares na Gravidez , Disfunção Ventricular Direita/tratamento farmacológico , Função Ventricular Direita/fisiologia , Cardiomiopatias/complicações , Cardiomiopatias/fisiopatologia , Relação Dose-Resposta a Droga , Ecocardiografia , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Antagonistas de Hormônios/administração & dosagem , Humanos , Imagem Cinética por Ressonância Magnética , Gravidez , Estudos Prospectivos , Resultado do Tratamento , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologia
12.
Intern Med ; 58(4): 541-544, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30568125

RESUMO

Peripartum cardiomyopathy (PPCM) is rare but life-threatening. We herein report the case of a 48-year-old woman with PPCM after oocyte donation and delivery of twins. Two weeks after delivery, she suffered from severe symptoms of heart failure [orthopnea, New York Heart Association (NYHA) class IV, pulmonary edema and a reduced left ventricular ejection fraction of 18%]. Although standard heart failure therapy was effective for diminishing the congestion, it was not sufficient to improve her symptoms or left ventricular systolic dysfunction. During admission, we added bromocriptine. A year later after the onset, she was in a good state with an improved left ventricular systolic function.


Assuntos
Bromocriptina/administração & dosagem , Bromocriptina/uso terapêutico , Cardiomiopatias/tratamento farmacológico , Doação de Oócitos/métodos , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Cardiomiopatias/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Período Periparto , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico
13.
J Cell Mol Med ; 22(12): 6368-6379, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30334324

RESUMO

Metformin (MET) is a diabetes drug that activates AMP-activated protein kinase (AMPK), and is suggested to have anticancer efficacy. Here, we investigated the role of AMPK signalling in prolactinoma (PRLoma), with particular respect to MET and bromocriptine (BC) as a PRLoma treatment. We analysed AMPK phosphorylation, dopamine D2 receptor (D2R), and oestrogen receptor (ER) expression in both BC-sensitive and -resistant PRLoma samples; effects of the AMPK agonist MET (alone or with BC) on in vitro proliferation and apoptosis, xenograft growth and prolactin (PRL) secretion of BC-sensitive and -resistant cells, and ER expression in xenografts. Some BC-resistant PRLomas showed high D2R expression but extremely low AMPK activation. MET significantly inhibited proliferation of cultured PRLoma cells; MET + BC notably restrained their PRL secretion. MET + BC further decreased tumour growth and serum PRL levels in xenografts than BC treatment alone. ER was down-regulated after AMPK activation in both cultured cells and xenografts. Together, we propose that the AMPK signalling pathway down-regulates ERα and ERß, and suppresses PRLoma growth as well as PRL secretion. Combined MET + BC is a potential treatment for PRLomas.


Assuntos
Metformina/administração & dosagem , Doenças da Hipófise/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Proteínas Quinases/genética , Receptores de Dopamina D2/genética , Animais , Apoptose/efeitos dos fármacos , Bromocriptina/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Xenoenxertos , Humanos , Camundongos , Fosforilação/efeitos dos fármacos , Doenças da Hipófise/genética , Doenças da Hipófise/patologia , Prolactina/genética , Prolactinoma/genética , Prolactinoma/patologia
14.
Mol Cancer Ther ; 17(9): 1859-1870, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29907594

RESUMO

Docetaxel resistance remains a major obstacle in the treatment of prostate cancer bone metastasis. In this study, we demonstrate that the dopamine D2 receptor (DRD2) agonist bromocriptine effectively enhances docetaxel efficacy and suppresses skeletal growth of prostate cancer in preclinical models. DRD2 is ubiquitously expressed in prostate cancer cell lines and significantly reduced in prostate cancer tissues with high Gleason score. Bromocriptine has weak to moderate cytotoxicity in prostate cancer cells, but effectively induces cell-cycle arrest. At the molecular level, bromocriptine inhibits the expression of c-Myc, E2F-1, and survivin and increases the expression of p53, p21, and p27. Intriguingly, bromocriptine markedly reduces androgen receptor levels, partially through Hsp90-mediated protein degradation. The combination of bromocriptine and docetaxel demonstrates enhanced in vitro cytotoxicity in prostate cancer cells and significantly retards the skeletal growth of C4-2-Luc tumors in mice. Collectively, these results provide the first experimental evidence for repurposing bromocriptine as an effective adjunct therapy to enhance docetaxel efficacy in prostate cancer. Mol Cancer Ther; 17(9); 1859-70. ©2018 AACR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Reposicionamento de Medicamentos , Neoplasias da Próstata/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/secundário , Bromocriptina/administração & dosagem , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Docetaxel/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Sinergismo Farmacológico , Humanos , Masculino , Camundongos Nus , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D2/metabolismo
15.
Clin Endocrinol (Oxf) ; 89(3): 346-353, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29894000

RESUMO

OBJECTIVE: Discontinuation of dopamine agonist (DA) treatment in women with prolactinoma after menopause is a potential approach; studies systematically assessing long-term outcomes are lacking. Our aim was to investigate the natural history of prolactinoma in this group. DESIGN/PATIENTS: Retrospective cohort study of women with prolactinoma diagnosed before menopause and who after menopause were not on DA. RESULTS: Thirty women were included. Twenty-eight received DA (median duration 18 years, median age at DA withdrawal 52 years). At last assessment (median follow-up 3 years) and compared with values 6-12 months after stopping DA, Prolactin (PRL) increased in 15%, decreased but not normalized in 33% and was normal in 52%; PRL levels or visible adenoma on imaging before DA withdrawal, treatment duration and presence of macro-/microadenoma at diagnosis were not predictors of normoprolactinaemia at last review, whereas PRL values 6-12 months after stopping DA were. Adenoma regrowth was detected in 2/27 patients (7%), who showed gradual increase in PRL. Comparison with 28 women who had DA withdrawal before their menopause revealed lower risk of hyperprolactinaemia recurrence in the postmenopausal group (HR:0.316, 95% CI: 0.101-0.985, P < .05). Two women with microprolactinoma diagnosed in perimenopausal period had not been offered DA; PRL decreased (but not normalized) during observation of 1 and 8 years. CONCLUSIONS: Prolactin normalized over time in nearly half of the women and serum PRL 6-12 months after DA withdrawal is useful predictor. Nonetheless, 7% of the patients demonstrated adenoma regrowth which, given the life expectancy postmenopause, necessitate regular monitoring of the cases with persistent hyperprolactinaemia.


Assuntos
Agonistas de Dopamina/uso terapêutico , Menopausa/fisiologia , Prolactinoma/tratamento farmacológico , Adolescente , Adulto , Bromocriptina/administração & dosagem , Bromocriptina/uso terapêutico , Cabergolina/administração & dosagem , Cabergolina/uso terapêutico , Agonistas de Dopamina/administração & dosagem , Ergolinas/administração & dosagem , Ergolinas/uso terapêutico , Feminino , Humanos , Pós-Menopausa , Prolactina/sangue , Prolactinoma/sangue , Estudos Retrospectivos , Suspensão de Tratamento , Adulto Jovem
16.
Neuroimage ; 169: 69-79, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29242106

RESUMO

Renewal is defined as the recovery of an extinguished response when the contexts of extinction and recall differ. Prominent hippocampal activity during context-related extinction can predict renewal. Dopaminergic antagonism during extinction learning impaired extinction and reduced hippocampal activation, without affecting renewal. However, to what extent dopaminergic stimulation during extinction influences hippocampal processing and renewal is as yet unknown. In this fMRI study, we investigated the effects of the dopamine D2-like agonist bromocriptine upon renewal in an associative learning task, in hippocampus and ventromedial PFC. We observed significant differences between bromocriptine (BROMO) and placebo (PLAC) treatments in the subgroups showing (REN) and lacking (NoREN) renewal: the renewal level of BROMO REN was significantly higher, and associated with more prominent hippocampal activation during extinction and recall, compared to PLAC REN and BROMO NoREN. Results suggest that an interaction between D2like-agonist-induced enhancement of hippocampal activity and a pre-existing tendency favoring context processing contributed to the higher renewal levels. In contrast, ventromedial prefrontal activation was unchanged, indicating that increased hippocampal context processing and not prefrontal response selection constituted the central driving force behind the high renewal levels. The findings demonstrate that hippocampal dopamine is important for encoding and providing of context information, and thus crucially involved in the renewal effect.


Assuntos
Bromocriptina/farmacologia , Agonistas de Dopamina/farmacologia , Extinção Psicológica/fisiologia , Neuroimagem Funcional/métodos , Hipocampo/fisiologia , Córtex Pré-Frontal/fisiologia , Adulto , Bromocriptina/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Extinção Psicológica/efeitos dos fármacos , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/efeitos dos fármacos , Humanos , Imagem por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/efeitos dos fármacos , Receptores de Dopamina D2/agonistas , Adulto Jovem
17.
Xenobiotica ; 48(10): 1028-1036, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28990837

RESUMO

1. Quercetin is a dietary flavonoid has extremely low water solubility and found to possess CYP3A inhibitory activity. The purpose of the present study was to evaluate the effect of quercetin and quercetin nanoparticles (NQC) on the pharmacokinetics of bromocriptine (BRO) in rats. 2. NQC prepared by antisolvent precipitation method and characterized by SEM and dissolution test. The following methods were used in this study i.e. in vitro liver and intestinal CYP3A microsomal activity and in vitro non-everted sac method. To confirm these findings, an in vivo pharmacokinetic study was also performed. 3. The results indicate that quercetin significantly (p < 0.05) inhibited the CYP3A activity in liver and intestinal microsomes. In non-everted sac study, the intestinal transport and Papp of BRO were significantly increased in NQC and quercetin groups. Furthermore, in vivo study revealed that the increased levels of Cmax and AUC were comparatively high in NQC pretreated group than quercetin group. In addition, pretreatment with quercetin and NQC significantly (p < 0.05) decreased the mean CL/F and Vd/F of BRO. 4. NQC pretreatment might be result in higher plasma levels of quercetin that could inhibit the CYP3A enzyme and enhanced the bioavailability of BRO.


Assuntos
Bromocriptina/farmacocinética , Inibidores do Citocromo P-450 CYP3A/farmacologia , Inibidores do Citocromo P-450 CYP3A/farmacocinética , Citocromo P-450 CYP3A/metabolismo , Intestinos/enzimologia , Fígado/enzimologia , Nanopartículas/química , Quercetina/farmacologia , Administração Oral , Animais , Transporte Biológico/efeitos dos fármacos , Bromocriptina/administração & dosagem , Bromocriptina/sangue , Bromocriptina/farmacologia , Calibragem , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Inibidores do Citocromo P-450 CYP3A/sangue , Masculino , Microssomos/efeitos dos fármacos , Microssomos/enzimologia , Nanopartículas/ultraestrutura , Permeabilidade , Ratos Wistar
18.
Pan Afr Med J ; 27: 278, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29187947

RESUMO

Macroprolactinemia is a polymeric form of prolactin-release, causing mildly symptomatic clinical pictures. The former can be isolated or associated with other causes of hyperprolactinemia. The association with an empty sella syndrome is rare. We report a case of a female patient discovered with this association. It's about a female patient 47 years old, followed up since the age of 31 years for bilateral galactorrhea and a spaniomenorrhea. There has been no associated drug intake. Her exploration has showed a serum prolactin level of 635 mIU/L. Thyroid test results were normal T4 = 10,2ng/L and TSH = 1.76 mIU/L. A brain scan has showed an empty sella turcica. Despite the unchanged levels of prolactinemia, the evolution under dopaminergic 5 mg /D has been marked by the occurrence of a pregnancy with persistent moderate hyperprolactinemia in the postpartum. Chromatography has showed a predominance of the macroprolactin form with: Prolactin monomer at 4.8%, Big Prolactin at 5% and Big Big Prolactin at 83%, thus stopping bromocriptine. Our observation suggests that macroprolactinemia can be associated with conventional etiologies of moderate hyperprolactinemia as the empty sella syndrome. Its detection would prevent the use of dopaminergic therapy which seems not useful.


Assuntos
Síndrome da Sela Vazia/diagnóstico , Hiperprolactinemia/etiologia , Prolactina/sangue , Bromocriptina/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Síndrome da Sela Vazia/complicações , Feminino , Humanos , Pessoa de Meia-Idade
19.
Eur Heart J ; 38(35): 2671-2679, 2017 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-28934837

RESUMO

Aims: An anti-angiogenic cleaved prolactin fragment is considered causal for peripartum cardiomyopathy (PPCM). Experimental and first clinical observations suggested beneficial effects of the prolactin release inhibitor bromocriptine in PPCM. Methods and results: In this multicentre trial, 63 PPCM patients with left ventricular ejection fraction (LVEF) ≤35% were randomly assigned to short-term (1W: bromocriptine, 2.5 mg, 7 days) or long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for 6 weeks) in addition to standard heart failure therapy. Primary end point was LVEF change (delta) from baseline to 6 months assessed by magnetic resonance imaging. Bromocriptine was well tolerated. Left ventricular ejection fraction increased from 28 ± 10% to 49 ± 12% with a delta-LVEF of + 21 ± 11% in the 1W-group, and from 27 ± 10% to 51 ± 10% with a delta-LVEF of + 24 ± 11% in the 8W-group (delta-LVEF: P = 0.381). Full-recovery (LVEF ≥ 50%) was present in 52% of the 1W- and in 68% of the 8W-group with no differences in secondary end points between both groups (hospitalizations for heart failure: 1W: 9.7% vs. 8W: 6.5%, P = 0.651). The risk within the 8W-group to fail full-recovery after 6 months tended to be lower. No patient in the study needed heart transplantation, LV assist device or died. Conclusion: Bromocriptine treatment was associated with high rate of full LV-recovery and low morbidity and mortality in PPCM patients compared with other PPCM cohorts not treated with bromocriptine. No significant differences were observed between 1W and 8W treatment suggesting that 1-week addition of bromocriptine to standard heart failure treatment is already beneficial with a trend for better full-recovery in the 8W group. Clinical trial registration: ClinicalTrials.gov, study number: NCT00998556.


Assuntos
Bromocriptina/administração & dosagem , Cardiomiopatias/tratamento farmacológico , Cardiotônicos/administração & dosagem , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Transtornos Puerperais/tratamento farmacológico , Adulto , Bromocriptina/efeitos adversos , Cardiotônicos/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Gravidez , Recuperação de Função Fisiológica/fisiologia , Resultado do Tratamento , Disfunção Ventricular Esquerda/tratamento farmacológico
20.
Breast J ; 23(6): 742-744, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28845595

RESUMO

There is increasing evidence associating idiopathic granulomatous mastitis (IGM) with hyperprolactinemia. All documented cases have involved the patient having at least one operative procedure before the association has been made. We present a 55 year old female with IGM associated with risperidone induced hyperprolactinemia. She was successfully treated with a dopamine agonist, bromocriptine. We demonstrated that complete resolution can be achieved without surgical intervention, by targeting serum prolactin levels. We hope this will increase awareness of this rare clinically entity and avoid potentially unnecessary surgery.


Assuntos
Bromocriptina/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Mastite Granulomatosa/diagnóstico , Hiperprolactinemia/diagnóstico , Bromocriptina/administração & dosagem , Diagnóstico Diferencial , Agonistas de Dopamina/administração & dosagem , Feminino , Mastite Granulomatosa/complicações , Mastite Granulomatosa/tratamento farmacológico , Humanos , Hiperprolactinemia/complicações , Hiperprolactinemia/tratamento farmacológico , Pessoa de Meia-Idade
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