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1.
Kardiologiia ; 60(6): 984, 2020 Jul 07.
Artigo em Russo | MEDLINE | ID: mdl-32720617

RESUMO

Aim      To evaluate the effect of bromocriptine on clinical hemodynamic and functional indexes and to analyze life prognosis for patients with periportal cardiomyopathy divided into two groups: group 1, bromocriptine treatment (n=21) and group 2, standard treatment without bromocriptine (n=22). History was taken, examination and standard clinical evaluation were performed, the Clinical Condition Scale (CCS with V.Yu. Mareev, 2000, modification) was administered, and 6-min walk test (6MWT) was performed. Quality of life was determined with the Minnesota questionnaire. Standard 12-lead electrocardiography, echocardiography, and blood biochemistry with measuring C-reactive protein (CRP) and prolactin, were performed. Follow-up duration was one year.Results Heart rate was significantly decreased in group 1 (22.7%) compared to group 2 (18%); the 6-min distance was increased (61 and 50 %, respectively), the total CCS score was decreased (66 and 55 %, respectively, and the quality of life Minnesota questionnaire score was improved (from 68.4±12.4 to 26.4±12.4 and from 63.4±10.9 to 36.4±15.1, respectively). Also, left ventricular (LV) end-diastolic dimension was reduced from 66.82±7.07 to 60.67±3.79 mm (9.2 %) in group 1 and from 61.92±4.41 to 58.91±4.68 mm (5 %) in group 2, which was associated with increases in LV ejection fraction by 18.3 and 14.5 %, respectively. In both groups, CRP concentration was decreased from 8.3±4.1 to 4.3±1.2 mg/l and from 8.5±3.5 to 6.3±1.5 mg/l, respectively. The bromocriptine treatment was associated with a significant decrease in prolactin level (62 %). The LV function completely recovered in 66.6% of patients in group 1 and in 27% of patients in group 2.Conclusion      The bromocriptine treatment of periportal cardiomyopathy in combination with an optimal drug therapy was associated with an additional beneficial effect on the clinical functional status, intracardiac hemodynamics, blood concentration of CRP, and a potentiality for complete recovery of the LV function.


Assuntos
Bromocriptina/uso terapêutico , Cardiomiopatias , Cardiomiopatias/tratamento farmacológico , Humanos , Período Periparto , Qualidade de Vida , Resultado do Tratamento
2.
Nature ; 584(7819): 125-129, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32528175

RESUMO

The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease1 and antipsychotic drugs2. DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine3, leading to stimulation of Gi and inhibition of adenylyl cyclase. Here we used cryo-electron microscopy to elucidate the structure of an agonist-bound activated DRD2-Gi complex reconstituted into a phospholipid membrane. The extracellular ligand-binding site of DRD2 is remodelled in response to agonist binding, with conformational changes in extracellular loop 2, transmembrane domain 5 (TM5), TM6 and TM7, propagating to opening of the intracellular Gi-binding site. The DRD2-Gi structure represents, to our knowledge, the first experimental model of a G-protein-coupled receptor-G-protein complex embedded in a phospholipid bilayer, which serves as a benchmark to validate the interactions seen in previous detergent-bound structures. The structure also reveals interactions that are unique to the membrane-embedded complex, including helix 8 burial in the inner leaflet, ordered lysine and arginine side chains in the membrane interfacial regions, and lipid anchoring of the G protein in the membrane. Our model of the activated DRD2 will help to inform the design of subtype-selective DRD2 ligands for multiple human central nervous system disorders.


Assuntos
Microscopia Crioeletrônica , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/química , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/ultraestrutura , Lipídeos de Membrana/metabolismo , Membranas Artificiais , Receptores de Dopamina D2/química , Receptores de Dopamina D2/ultraestrutura , Bromocriptina/química , Bromocriptina/metabolismo , Dopamina/química , Dopamina/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Humanos , Lipídeos de Membrana/química , Modelos Moleculares , Conformação Proteica , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D2/metabolismo , Transdução de Sinais
4.
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
5.
Am J Physiol Endocrinol Metab ; 318(1): E62-E71, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31794265

RESUMO

Bromocriptine, a dopamine D2 receptor agonist originally used for the treatment of hyperprolactinemia, is largely successful in reducing hyperglycemia and improving glucose tolerance in type 2 diabetics. However, the mechanism behind bromocriptine's effect on glucose intolerance is unclear. Here, we tested three hypotheses, that bromocriptine may exert its effects on glucose metabolism by 1) decreasing prolactin secretion, 2) indirectly increasing activity of key melanocortin receptors in the central nervous system, or 3) improving/restoring circadian rhythms. Using a diet-induced obese (DIO) mouse model, we established that a 2-wk treatment of bromocriptine is robustly effective at improving glucose tolerance. We then demonstrated that bromocriptine is effective at improving the glucose tolerance of both DIO prolactin-deficient and melanocortin-4 receptor (MC4R)-deficient mice, pointing to bromocriptine's ability to affect glucose tolerance independently of prolactin or MC4R signaling. Finally, we tested bromocriptine's dependence on the circadian system by testing its effectiveness in environmental (e.g., repeated shifts to the light-dark cycle) and genetic (e.g., the Clock mutant mouse) models of circadian disruption. In both models of circadian disruption, bromocriptine was effective at improving glucose tolerance, indicating that a functional or well-aligned endogenous clock is not necessary for bromocriptine's effects on glucose metabolism. Taken together, these results do not support the role of prolactin, MC4R, or the circadian clock as integral to bromocriptine's underlying mechanism. Instead, we find that bromocriptine is a robust diabetic treatment and resilient to genetically induced obesity, diabetes, and circadian disruption.


Assuntos
Glicemia/efeitos dos fármacos , Bromocriptina/farmacologia , Agonistas de Dopamina/farmacologia , Obesidade/metabolismo , Animais , Glicemia/metabolismo , Proteínas CLOCK/genética , Ritmo Circadiano , Dieta Hiperlipídica , Modelos Animais de Doenças , Teste de Tolerância a Glucose , Insulina/metabolismo , Camundongos , Camundongos Knockout , Mutação , Prolactina/genética , Receptor Tipo 4 de Melanocortina/genética
6.
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
7.
Anat Sci Int ; 95(2): 277-285, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31865549

RESUMO

Several investigations have shown that pregnancy and lactation are able to induce elongation of long bone by altering epiphyseal cartilage function in a prolactin-dependent manner. Since the transcription factor Sox9 is of utmost importance for chondrocyte proliferation and differentiation and since bromocriptine, a dopaminergic D2 agonist widely used to suppress milk production, is known to disrupt the production and release of prolactin, we herein aimed to investigate whether pregnancy and lactation as well as bromocriptine could alter the expression of Sox9. Our immunohistochemical analysis showed that the Sox9 expression levels were markedly upregulated in the tibial proliferative zone of day 21 pregnant rats. In day 8 (early) and day 14 (mid) lactating rats, the Sox9 expression was enhanced only in the proliferative zone, but not in the resting and hypertrophic zones. There was no change in Sox9 expression in day 21 (late) lactating rats. Postweaning rats manifested a decreased Sox9 expression in the hypertrophic zone. Bromocriptine had no effect on Sox9 expression in the proliferative zone of day 21 pregnant rats; however, it completely prevented the Sox9 upregulation in those of early and mid-lactating rats. A differential response was observed in the proliferative and hypertrophic zones of late lactating rats, in which bromocriptine enhanced Sox9 expression. Further investigation of cartilaginous matrix revealed no change in proteoglycans accumulation in lactating rats. In conclusion, the upregulated Sox9 expression predominantly occurred in the proliferative zone during late pregnancy and early and mid-lactation, while the bromocriptine effects depended on the periods and epiphyseal zones.


Assuntos
Bromocriptina/farmacologia , Expressão Gênica/efeitos dos fármacos , Lâmina de Crescimento/metabolismo , Lactação/metabolismo , Prenhez/metabolismo , Proteoglicanas/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Animais , Feminino , Lactação/genética , Gravidez , Prenhez/genética , Ratos , Regulação para Cima/efeitos dos fármacos
8.
Pituitary ; 22(6): 581-593, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31522359

RESUMO

PURPOSE: Somatostatin analogs (SSAs) represent a mainstay of medical treatment for acromegaly, currently available as either intramuscular or deep subcutaneous injections. Patient-reported outcomes (PROs) are increasingly common as relevant outcomes in studies of acromegaly and its treatment, but there are no validated PRO measures available that focus on the disease burden and the impact of treatment, specifically designed for use in patients with acromegaly. We sought to develop a new and unique PRO measure, the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ). METHODS: Concept elicitation (CE) interviews were conducted with acromegaly patients in the United States receiving SSA injections at a stable dose for ≥ 6 months. A questionnaire was drafted based on these interviews; combined CE and cognitive debriefing (CE/CD) interviews were then conducted to confirm the content, clarity, and relevance of the questionnaire. RESULTS: Nineteen subjects completed interviews [n = 9 CE, n = 10 CE/CD; n = 15 Lanreotide Depot/Autogel (Somatuline), n = 4 Octreotide LAR (Sandostatin LAR)]. Most subjects responded positively when asked about the effectiveness of their current treatment; however, breakthrough symptoms, injection site reactions, and side effects were commonly reported and had negative impacts on social and emotional well-being and daily activities. All 10 subjects involved in debriefing interviews found the questionnaire to be relevant, easy to complete, and found the response options to be clear. The resulting 26-item Acro-TSQ covers symptoms and symptom control, gastrointestinal side effects and their impact on daily activities, the emotional impact of treatment, convenience and ease of use, and overall satisfaction. CONCLUSIONS: The Acro-TSQ is a novel PRO, focused on both disease burden and impact of treatment; it was found to be comprehensive, clear, and relevant for patients with acromegaly receiving injectable SSA treatment.


Assuntos
Acromegalia/tratamento farmacológico , Adulto , Bromocriptina/uso terapêutico , Cabergolina/uso terapêutico , Feminino , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Satisfação Pessoal , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Inquéritos e Questionários
9.
Am J Audiol ; 28(3): 548-552, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31430172

RESUMO

Objective Current recommendations for cochlear hydrops treatment include systemic glucocorticoids and diuretics. Cochlear cells express dopamine receptors, although their role is unknown in the pathophysiology of cochlear hydrops. Case Description We report the case of remission of recurrent right-sided cochlear hydrops in a young male patient treated with bromocriptine due to pituitary macroprolactinoma. Transient improvement was observed after oral steroid and diuretic treatment, but cochlear hydrops recurred until the dose of bromocriptine was increased to 10 mg daily. Conclusion Bromocriptine may stimulate dopamine receptors in cochlear cells with potential therapeutic role in patients with cochlear hydrops. There are no widely accepted and effective treatments for endolymphatic hydrops, and identifying potential new and efficacious therapeutics is of high relevance.


Assuntos
Bromocriptina/uso terapêutico , Doenças Cocleares/tratamento farmacológico , Perda Auditiva Neurossensorial/tratamento farmacológico , Antagonistas de Hormônios/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Adulto , Audiometria de Tons Puros , Doenças Cocleares/complicações , Diuréticos/uso terapêutico , Furosemida/uso terapêutico , Glucocorticoides/uso terapêutico , Perda Auditiva Neurossensorial/complicações , Humanos , Imagem por Ressonância Magnética , Masculino , Metilprednisolona/uso terapêutico , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Prolactinoma/complicações , Prolactinoma/diagnóstico por imagem , Prolactinoma/patologia , Recidiva
10.
Horm Behav ; 116: 104582, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31445012

RESUMO

Parental care can include two general types of behavior: (1) aggressive behavior, which is used to defend offspring from predators; and (2) nurturing behavior, which is used to provide offspring with environmental conditions or resources necessary for survival. Many studies have implicated androgens in promoting aggressive behavior and prolactin in promoting nurturing behavior. We experimentally manipulated these hormones to investigate their effects on parental care behavior in bluegill (Lepomis macrochirus). Parental males, which provide sole care to the developing eggs and larvae, received an implant with an androgen (11-ketotestosterone [11-KT]), an androgen antagonist (flutamide), prolactin, a prolactin-release inhibitor (bromocriptine), or castor oil (placebo). We found that 11-KT implants led to a significant increase in the frequency of aggressive behavior directed towards a simulated brood predator, and were associated with a nearly significant decrease in the frequency of nurturing behavior directed towards the developing eggs. In contrast, prolactin implants were associated with a significant increase in the frequency of nurturing behavior, but also reduced the frequency of aggressive behavior directed towards the simulated brood predator. These results suggest a hormone-mediated mechanistic trade-off between nurturing and aggressive behavior, whereby parental males are unable to be both highly nurturing and highly aggressive.


Assuntos
Agressão/efeitos dos fármacos , Androgênios/farmacologia , Comportamento de Nidação/efeitos dos fármacos , Comportamento Paterno/efeitos dos fármacos , Perciformes , Prolactina/farmacologia , Animais , Bromocriptina/farmacologia , Peixes/fisiologia , Flutamida/farmacologia , Larva , Masculino , Perciformes/fisiologia , Comportamento Social , Testosterona/análogos & derivados , Testosterona/farmacologia
11.
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
12.
Intern Med ; 58(21): 3125-3128, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31243214

RESUMO

A 22-year-old Japanese woman consulted an endocrinologist due to persistent galactorrhea for the past 10 months. She had hyperprolacinemia and had previously been diagnosed with type 2 diabetes mellitus based on her glycohemoglobin level of 11.6%. After two months, she was admitted to our hospital and finally diagnosed with prolactinoma. For the treatment of prolactinoma, bromocriptine 2.5 mg/day was started. After seven days, her post-prandial blood glucose levels, homeostasis model assessment of insulin resistance and plasma C-peptide levels were significantly improved. These results indicate that traditional bromocriptine can be an effective therapeutic alternative in patients with prolactinoma complicated with type 2 diabetes.


Assuntos
Bromocriptina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Antagonistas de Hormônios/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Amenorreia , Diabetes Mellitus Tipo 2/complicações , Feminino , Galactorreia/tratamento farmacológico , Galactorreia/etiologia , Humanos , Imagem por Ressonância Magnética , Hipófise/diagnóstico por imagem , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Prolactina/sangue , Prolactinoma/complicações , Prolactinoma/diagnóstico por imagem , Adulto Jovem
13.
BMJ Case Rep ; 12(6)2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31213433

RESUMO

While neuroleptic malignant syndrome (NMS) is typically characterised by delirium, motor rigidity, fever and dysautonomia, the syndrome is not pathognomonic, and NMS remains a diagnosis of exclusion. Here, we describe the case of a 44-year-old woman, with no relevant psychiatric history, admitted to a nephrology unit due to acute renal failure. After administration of antipsychotics, she presented with mental status alteration, generalised tremor, rigidity and autonomic nervous system dysfunction. Fever and rhabdomyolysis, however, were not prominent, and NMS was not considered initially in the differential diagnosis. The resulting delay in diagnosis, with continued administration of antipsychotics, led to progressive clinical deterioration. Once NMS was considered, however, antipsychotics were withdrawn and the patient was treated with electroconvulsive therapy (ECT), followed by administration of a dopamine receptor agonist, with close to full remission of all symptoms. Importantly, during outpatient follow-up, sustained mild and asymmetric tremor and rigidity was noted, leading to a diagnosis of Parkinson's disease. While this raises questions regarding differential diagnosis between NMS in Parkinson's disease, versus worsening of Parkinson's disease due to antipsychotic treatment, the former is supported by the acute and rapidly progressive onset of exuberant autonomic dysfunction and clouded conscience, after administration of a neuroleptic. Ultimately, a definitive distinction between these two alternatives for diagnosis of the inaugural neurological presentation in this patient is not possible. Nevertheless, we believe this case illustrates that NMS can be easily missed, particularly in atypical cases, delaying appropriate treatment, and that a flexible multimodal treatment approach, involving ECT, should be considered for complex clinical cases. Furthermore, it also underlines the importance of post-NMS follow-up, to investigate underlying neurological or medical disorders, particularly in those patients who do not have a full recovery.


Assuntos
Lesão Renal Aguda/terapia , Anticonvulsivantes/uso terapêutico , Antipsicóticos/uso terapêutico , Bromocriptina/uso terapêutico , Lorazepam/uso terapêutico , Síndrome Maligna Neuroléptica/diagnóstico , Lesão Renal Aguda/fisiopatologia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Síndrome Maligna Neuroléptica/tratamento farmacológico , Síndrome Maligna Neuroléptica/fisiopatologia , Diálise Renal , Resultado do Tratamento
14.
Breast J ; 25(5): 974-976, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31165510

RESUMO

Lactating adenomas are painful, benign breast lesions, typically presenting during pregnancy and treated with surgery. Here we present a case of a 25-year-old pregnant woman who developed multiple, bilateral lactating adenomas and was successfully treated during her third trimester with bromocriptine alone. Bromocriptine, a dopamine agonist, may be used in pregnancy to effectively treat lactating adenomas in lieu of surgery.


Assuntos
Adenoma/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Bromocriptina/uso terapêutico , Antagonistas de Hormônios/uso terapêutico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Adulto , Feminino , Humanos , Dor/tratamento farmacológico , Gravidez , Terceiro Trimestre da Gravidez
15.
World Neurosurg ; 129: e686-e694, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31181361

RESUMO

OBJECTIVE: First-line treatment for prolactin-producing pituitary adenomas is dopamine agonist (DA) therapy. This is the first study to analyze the rate of radiographic and hormonal regression of prolactinomas in response to DA therapy to better understand what time frame we consider DA treatment failure. METHODS: We searched the electronic medical records of 3 tertiary care medical institutions for patients with prolactinomas. The primary outcome was tumor volume and prolactin (PRL) levels at various time points. The secondary outcome was indicators of treatment failure. Modeling by both linear and exponential models was tested to determine potential predictors of response magnitude and treatment failure by multivariate and regression analyses respectively. RESULTS: There were 99 patients (53% male) included in this analysis. The mean patient age was 42.7 years ± 14.5, and mean width/volume of tumor at diagnosis was 12.3 mm and 1.3 cm3, respectively. The mean PRL level at diagnosis was 593.2 ng/mL (79-7913). Modeling indicated a plateau at 68.2% initial volume (95% confidence interval 61.7-73.5) by 12.6 months and a PRL plateau of 21.4 ng/mL (95% confidence interval 0-92.5) by 3.3 months. Multivariate analyses revealed male sex (odds ratio 0.168; P = 0.036) to be a predictor of faster PRL response to DA therapy. CONCLUSIONS: Prolactinomas plateau in PRL levels and the rate of size regression within the first year of DA treatment. Prolactinomas with lack of size regression and failure to reach normalization of PRL levels by 12 months may be considered for other management strategies.


Assuntos
Bromocriptina/uso terapêutico , Cabergolina/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Prolactina/sangue , Prolactinoma/tratamento farmacológico , Adulto , Progressão da Doença , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Prolactinoma/sangue , Prolactinoma/diagnóstico por imagem , Prolactinoma/patologia , Fatores Sexuais , Falha de Tratamento , Carga Tumoral
16.
Pharmazie ; 74(5): 286-289, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31109398

RESUMO

Various types of fluorescent lights are found in the dispensing rooms of medical facilities, such as hospitals and pharmacies, in Japan. However, to reduce electric power consumption, it was necessary to evaluate the substitution of fluorescent lighting with light emitting diode (LED) lighting, which has become widespread in recent years. We subjectively evaluated several types of medicines stored under various light sources and found that different color changes were induced in tablets. In this study, we focused on Perlodel ® tablets, containing 2.5 mg bromocriptine mesylate, as an example for the objective evaluation of the differences in the color change of tablets when stored under LED lighting and fluorescent lighting. High-performance liquid chromatography (HPLC) analysis of part of the tablet surface area revealed a change from white to light brown or dark brown after 28 days of irradiation, with a residual concentration of bromocriptine mesylate of 85.5 % under fluorescent lighting, 85.6 % under daylight-color LED lighting, 90.3 % under bulb-color LED lighting, and 99.2 % in the dark. In addition, the ultraviolet (UV)-visible spectral study of the absorbance of a photo-product at 400-550 nm indicated that the color change of the Perlodel® 2.5 mg tablet was caused by photochemical degradation of bromocriptine mesylate. Thus, this analysis of the photochemical changes in drugs stored under different light sources demonstrated the potency of LED lights. Through the objective evaluation of the color change, the cause of the color change was determined; this will allow us to develop a strategy that minimizes possible disadvantages to patients, such as a decrease in treatment efficacy owing to decomposition of the main component or adverse caused by decomposed matter.


Assuntos
Bromocriptina/química , Bromocriptina/efeitos da radiação , Cromatografia Líquida de Alta Pressão , Cor , Estabilidade de Medicamentos , Iluminação , Fotólise , Comprimidos/química , Comprimidos/efeitos da radiação , Temperatura
17.
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
18.
Endocr Pract ; 25(4): 340-352, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30995432

RESUMO

Objective: To describe outcomes of patients with giant prolactinoma (≥4 cm) and identify predictors of therapeutic response. Methods: In this retrospective study, complete biochemical and structural response were defined as prolactin (PRL) ≤25 ng/mL and no visible tumor at follow-up, respectively. Results: Giant prolactinoma (median size, 4.8 cm [range, 4 to 9.8 cm]; median PRL, 5,927 ng/mL [range, 120 to 100,000 ng/mL]) was diagnosed in 71 patients. Treatments included: dopamine agonists (DAs) (n = 70, 99%), surgery (n = 30, 42%), radiation (n = 10, 14%), and somatostatin analogs (n = 2, 3%). Patients treated with DA monotherapy were older compared with those who received subsequent therapies (47 years vs. 28 years; P = .003) but had similar initial PRL and tumor size. Surgically managed patients were younger compared with the nonsurgical group (35 years vs. 46 years; P = .02) and had lower initial PRL (3,121 ng/mL vs. 6,920 ng/mL; P = .02), yet they had similar tumor response. Hypopituitarism was more common following surgery compared to medical management: adrenal insufficiency (69% vs. 27%; P<.001), hypothyroidism (67% vs. 38%; P = .02), growth hormone deficiency (24% vs. 6%; P = .04), and diabetes insipidus (17% vs. 3%; P = .04). Therapeutic response did not correlate with sex, age, initial PRL, tumor size, or first-line therapy mode. At median follow-up of 4.8 years, the median PRL was 18.3 ng/mL (range, 0.6 to 12,680 ng/mL), and final volume was 0.9 cm3 (range, 0 to 43.0 cm3). In those with available data, 36/65 (55%) patients achieved PRL normalization, and 16/61 (26%) had no visible tumor at follow-up. Conclusion: Most patients with giant prolactinoma have excellent response to DA. Sex, age, initial PRL, and tumor size do not predict therapeutic response. Abbreviations: BRC = bromocriptine; CAB = cabergoline; CSF = cerebrospinal fluid; DA = dopamine agonist; MRI = magnetic resonance imaging; PRL = prolactin.


Assuntos
Neoplasias Hipofisárias , Prolactinoma , Adulto , Bromocriptina , Agonistas de Dopamina , Ergolinas , Humanos , Pessoa de Meia-Idade , Prolactina , Estudos Retrospectivos
19.
Invest Ophthalmol Vis Sci ; 60(5): 1442-1453, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30947334

RESUMO

Purpose: The purpose of this study was to test the extent of light damage in different models of night blindness and apply these paradigms in testing the therapeutic efficacy of combination therapy by drugs acting on the Gi, Gs, and Gq protein-coupled receptors. Methods: Acute bright light exposure was used to test susceptibility to light damage in mice lacking the following crucial phototransduction proteins: rod transducin (GNAT1), cone transducin (GNAT2), visual arrestin 1 (ARR1), and rhodopsin kinase 1 (GRK1). Mice were intraperitoneally injected with either vehicle or drug combination consisting of metoprolol (ß1-receptor antagonist), bromocriptine (dopamine family-2 receptor agonist) and tamsulosin (α1-receptor antagonist) before bright light exposure. Light damage was primarily assessed with optical coherence tomography and inspection of cone population in retinal whole mounts. Retinal inflammation was assessed in a subset of experiments using autofluorescence imaging by scanning laser ophthalmoscopy and by postmortem inspection of microglia and astrocyte activity. Results: The Gnat1-/- mice showed slightly increased susceptibility to rod light damage, whereas the Gnat2-/- mice were very resistant. The Arr1-/- and Grk1-/- mice were sensitive for both rod and cone light damage and showed robust retinal inflammation 7 days after bright light exposure. Pretreatment with metoprolol + bromocriptine + tamsulosin rescued the retina in all genetic backgrounds, starting at doses of 0.2 mg/kg metoprolol, 0.02 mg/kg bromocriptine, and 0.01 mg/kg tamsulosin in the Gnat1-/- mice. The therapeutic drug doses increased in parallel with light-damage severity. Conclusions: Our results suggest that congenital stationary night blindness and Oguchi disease patients can be at an elevated risk of the toxic effects of bright light. Furthermore, systems pharmacology drug regimens that stimulate Gi signaling and attenuate Gs and Gq signaling present a promising disease-modifying therapy for photoreceptor degenerative diseases.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Bromocriptina/farmacologia , Luz/efeitos adversos , Metoprolol/farmacologia , Cegueira Noturna/tratamento farmacológico , Tansulosina/farmacologia , Animais , Arrestinas/deficiência , Modelos Animais de Doenças , Receptor Quinase 1 Acoplada a Proteína G/deficiência , Camundongos , Transducina/deficiência , Estados Unidos , United States Food and Drug Administration
20.
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
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