Timed Bromocriptine-QR Therapy Reduces Progression of Cardiovascular Disease and Dysglycemia in Subjects with Well-Controlled Type 2 Diabetes Mellitus.

PubMed

Chamarthi, Bindu; Gaziano, J Michael; Blonde, Lawrence; Vinik, Aaron; Scranton, Richard E; Ezrokhi, Michael; Rutty, Dean; Cincotta, Anthony H

2015-01-01

Type 2 diabetes (T2DM) patients, including those in good glycemic control, have an increased risk of cardiovascular disease (CVD). Maintaining good glycemic control may reduce long-term CVD risk. However, other risk factors such as elevated vascular sympathetic tone and/or endothelial dysfunction may be stronger potentiators of CVD. This study evaluated the impact of bromocriptine-QR, a sympatholytic dopamine D2 receptor agonist, on progression of metabolic disease and CVD in T2DM subjects in good glycemic control (HbA1c ≤ 7.0%). 1834 subjects (1219 bromocriptine-QR; 615 placebo) with baseline HbA1c ≤ 7.0% derived from the Cycloset Safety Trial (this trial is registered with ClinicalTrials.gov Identifier: NCT00377676), a 12-month, randomized, multicenter, placebo-controlled, double-blind study in T2DM, were evaluated. Treatment impact upon a prespecified composite CVD endpoint (first myocardial infarction, stroke, coronary revascularization, or hospitalization for angina/congestive heart failure) and the odds of losing glycemic control (HbA1c >7.0% after 52 weeks of therapy) were determined. Bromocriptine-QR reduced the CVD endpoint by 48% (intention-to-treat; HR: 0.52 [0.28-0.98]) and 52% (on-treatment analysis; HR: 0.48 [0.24-0.95]). Bromocriptine-QR also reduced the odds of both losing glycemic control (OR: 0.63 (0.47-0.85), p = 0.002) and requiring treatment intensification to maintain HbA1c ≤ 7.0% (OR: 0.46 (0.31-0.69), p = 0.0002). Bromocriptine-QR therapy slowed the progression of CVD and metabolic disease in T2DM subjects in good glycemic control.

Impact of Bromocriptine-QR Therapy on Glycemic Control and Daily Insulin Requirement in Type 2 Diabetes Mellitus Subjects Whose Dysglycemia Is Poorly Controlled on High-Dose Insulin: A Pilot Study

PubMed Central

Roe, Erin D.; Chamarthi, Bindu; Raskin, Philip

2015-01-01

Background. The concurrent use of a postprandial insulin sensitizing agent, such as bromocriptine-QR, a quick release formulation of bromocriptine, a dopamine D2 receptor agonist, may offer a strategy to improve glycemic control and limit/reduce insulin requirement in type 2 diabetes (T2DM) patients on high-dose insulin. This open label pilot study evaluated this potential utility of bromocriptine-QR. Methods. Ten T2DM subjects on metformin (1-2 gm/day) and high-dose (TDID ≥ 65 U/day) basal-bolus insulin were enrolled to receive once daily (morning) bromocriptine-QR (1.6–4.8 mg/day) for 24 weeks. Subjects with at least one postbaseline HbA1c measurement (N = 8) were analyzed for change from baseline HbA1c, TDID, and postprandial glucose area under the curve of a four-hour mixed meal tolerance test (MMTT). Results. Compared to the baseline, average HbA1c decreased 1.76% (9.74 ± 0.56 to 7.98 ± 0.36, P = 0.01), average TDID decreased 27% (199 ± 33 to 147 ± 31, P = 0.009), and MMTT AUC60–240 decreased 32% (P = 0.04) over the treatment period. The decline in HbA1c and TDID was observed at 8 weeks and sustained over the remaining 16-week study duration. Conclusion. In this study, bromocriptine-QR therapy improved glycemic control and meal tolerance while reducing insulin requirement in T2DM subjects poorly controlled on high-dose insulin therapy. PMID:26060825

Effect of bromocriptine-QR on glycemic control in subjects with uncontrolled hyperglycemia on one or two oral anti-diabetes agents.

PubMed

Vinik, Aaron I; Cincotta, Anthony H; Scranton, Richard E; Bohannon, Nancy; Ezrokhi, Michael; Gaziano, J Michael

2012-01-01

To investigate the effect of Bromocriptine-QR on glycemic control in patients with type 2 diabetes whose glycemia is poorly controlled on one or two oral anti-diabetes agents. Five hundred fifteen Type 2 Diabetes Mellitus (T2DM) subjects (ages 18 to 80 and average body mass index [BMI] of 32.7) with baseline HbA1c ≥ 7.5 and on one or two oral anti-diabetes (OAD) medications (metformin, sulfonylurea, and/or thiazolidinediones) were randomized 2:1 to bromocriptine-QR (1.6 to 4.8 mg/day) or placebo for a 24 week treatment period. Study investigators were allowed to adjust, if necessary, subject anti-diabetes medications during the study to attempt to achieve glycemic control in case of glycemic deterioration. The impact of bromocriptine-QR treatment intervention on glycemic control was assessed in subjects on any one or two OADs (ALL treatment category) (N = 515), or on metformin with or without another OAD (Met/OAD treatment category) (N = 356), or on metformin plus a sulfonylurea (Met/SU treatment category) (N = 245) 1) by examining the between group difference in change from baseline a) concomitant OAD medication changes during the study, and b) HbA1c and 2) by determining the odds of reaching HbA1c of ≤ 7.0% on bromocriptine-QR versus placebo. Significantly more patients (approximately 1.5 to 2-fold more; P<.05) intensified concomitant anti-diabetes medication therapy during the study in the placebo versus the bromocriptine-QR arm. In subjects that did not change the intensity of the baseline diabetes therapy (72%), and that were on any one or two OADs (ALL), or on metformin with or without another OAD (Met/OAD), or on metformin plus sulfonylurea (Met/SU), the HbA1c change for bromocriptine-QR versus placebo was -0.47 versus +0.22 (between group delta of -0.69, P<.0001), -0.55 versus +0.26 (between group delta of -0.81, P<.0001) and -0.63 versus +0.20 (between group delta of -0.83, P<.0001) respectively, after 24 weeks on therapy. The odds ratio of reaching HbA1c of ≤ 7.0% was 6.50, 12.03 and 11.45 (P<.0002) for these three groups, respectively. In T2DM subjects whose hyperglycemia is poorly controlled on one or two oral agents, bromocriptine-QR therapy for 24 weeks can provide significant added improvement in glycemic control relative to adding placebo.

Effect of bromocriptine on acute ethanol tolerance in UChB rats.

PubMed

Tampier, L; Prado, C; Quintanilla, M E; Mardones, J

1999-07-01

It has been suggested that a higher capacity to develop acute tolerance during a single dose of ethanol may promote higher ethanol consumption in alcohol-preferring rodents. Several studies have shown that the dopaminergic system may be involved in voluntary ethanol consumption. In the present paper we studied the effect of bromocriptine, a dopaminergic agonist drug, that is known to reduce voluntary consumption of ethanol, on acute tolerance in high (UChB) ethanol consumer rats. Acute tolerance was evaluated in bromocriptine and saline-treated rats by motor impairment induced by a subnarcotic dose of ethanol of 2.3 g/kg IP using a modified tilting plane test. Results showed a highly significant positive correlation between acute tolerance and the voluntary ethanol consumption by the rat. Bromocriptine treatment decreased ethanol consumption and also decreased acute tolerance development. This adds further support to the postulate that the acquisition of acute tolerance to ethanol may promote increased alcohol consumption. Moreover, these results also suggest that dopaminergic receptors involved in ethanol voluntary consumption may also be in acute tolerance development.

DRD2 genotype predicts prefrontal activity during working memory after stimulation of D2 receptors with bromocriptine.

PubMed

Gelao, Barbara; Fazio, Leonardo; Selvaggi, Pierluigi; Di Giorgio, Annabella; Taurisano, Paolo; Quarto, Tiziana; Romano, Raffaella; Porcelli, Annamaria; Mancini, Marina; Masellis, Rita; Ursini, Gianluca; De Simeis, Giuseppe; Caforio, Grazia; Ferranti, Laura; Lo Bianco, Luciana; Rampino, Antonio; Todarello, Orlando; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

2014-06-01

Pharmacological stimulation of D2 receptors modulates prefrontal neural activity associated with working memory (WM) processing. The T allele of a functional single-nucleotide polymorphism (SNP) within DRD2 (rs1076560 G > T) predicts reduced relative expression of the D2S receptor isoform and less efficient neural cortical responses during WM tasks. We used functional MRI to test the hypothesis that DRD2 rs1076560 genotype interacts with pharmacological stimulation of D2 receptors with bromocriptine on prefrontal responses during different loads of a spatial WM task (N-Back). Fifty-three healthy subjects (38 GG and 15 GT) underwent two 3-T functional MRI scans while performing the 1-, 2- and 3-Back versions of the N-Back WM task. Before the imaging sessions, either bromocriptine or placebo was administered to all subjects in a counterbalanced order. A factorial repeated-measures ANOVA within SPM8 (p < 0.05, family-wise error corrected) was used. On bromocriptine, GG subjects had reduced prefrontal activity at 3-Back together with a significant decrement in performance, compared with placebo. On the other hand, GT subjects had lower activity for the same level of performance at 1-Back but a trend for reduced behavioral performance in the face of unchanged activity at 2-Back. These results indicate that bromocriptine stimulation modulates prefrontal activity in terms of disengagement or of efficiency depending on DRD2 genotype and working memory load.

Case-control cytogenetic study in offspring of mothers treated with bromocriptine during early pregnancy.

PubMed

Czeizel, A; Kiss, R; Rácz, K; Mohori, K; Gláz, E

1989-01-01

The distribution of modal and non-modal karyotypes was examined in mitoses of lymphocyte cultures of 31 children who had been exposed to bromocriptine in utero, and in 31 matched controls. No mosaicism was diagnosed. Furthermore, no more hypomodal cells occurred in the study group than in the control group.

Focusing on cardiovascular disease in type 2 diabetes mellitus: an introduction to bromocriptine QR.

PubMed

Bell, David S

2012-09-01

Cardiovascular risk reduction is a key priority in patients with diabetes. The relationship between glycemic control and macrovascular outcomes, such as the benefit of intensive glucose control and the importance of postprandial or fasting blood glucose, is still under debate. A number of pharmacologic options are available to treat type 2 diabetes mellitus and these options have differing evidence for their cardiovascular safety. In this article, the novel agent bromocriptine quick release is discussed. Recently approved, this once-daily treatment provides glycemic control as monotherapy or in combination with other antihyperglycemic medications and has been shown in a prospective phase 3 safety study to not increase cardiovascular risk. Therefore, bromocriptine quick release increases the range of options available to treat patients with type 2 diabetes mellitus without increasing cardiovascular risk.

A review of dopamine agonist therapy in type 2 diabetes and effects on cardio-metabolic parameters.

PubMed

Lamos, E M; Levitt, D L; Munir, K M

2016-02-01

Dopamine action appears to play a role in changes that are seen in obesity, metabolic syndrome and type 2 diabetes mellitus. Bromocriptine-QR (Quick Release), a dopamine agonist, is approved for use in treatment of type 2 diabetes. It has demonstrated modest improvement in glycemic parameters, cholesterol and weight in certain cohorts. Limited data using cabergoline, a long-acting dopamine agonist, also demonstrate glycemic efficacy. Additionally, bromocriptine-QR appears to have a favorable cardiovascular risk reduction. The direct mechanism by which bromocriptine-QR, or central dopamine agonism, achieves modest glycemic control and favorable cardio-metabolic profile is unclear. This relationship appears to be more complex than the historical explanation of "resetting" the circadian clock and may further be elucidated using data in individuals with hyperprolactinemia and prolactinoma. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Evaluation of the efficacy and safety of bromocriptine QR in type 2 diabetes.

PubMed

Ramteke, Karuna Balwant; Ramanand, Sunita Jaiprakash; Ramanand, Jaiprakash B; Jain, Suyog Subhas; Raparti, Girish Tulsidas; Patwardhan, Milind Hari; Murthy, Mangala; Ghanghas, Ravi G

2011-07-01

Diabetes mellitus is a chronic metabolic disorder of endocrinal origin with multiorgan involement. Today's physician has a lot many options to choose for treating type 2 diabetes, but does not always manages to achieve optimal glycemic control. The newer drug bromocriptine acts by novel hypothalamic circadian rhythm resetting mechanism. To evaluate the efficacy and safety of bromocriptine QR in type 2 diabetes. 105 patients according to inclusion and exclusion criteria were randomized into three groups by simple randomization. Group 1 received bromocriprine 2.4 mg once daily, group 2 received metformin 500 mg twice daily while group 3 received bromocriprine 1.6 mg daily and metformin 500 mg twice daily. Baseline measurement of fasting and postprandial blood sugar, HbA1(C) and BMI were followed up at 6(th) and 12(th) weeks. Safety evaluation was done by questioning the patient and also through routine hematological and biochemical parameters. Z test was used for analysis. Group 1 showed significant reduction in fasting and postprandial sugar and HbA(1c) at 12 weeks. While groups 2 and 3 showed even higher reduction in these parameters albeit with slightly more adverse drug events like nausea, vomiting compared to group 1. Bromocriptine QR is an effective and safe antidiabetic drug which can be employed as monotherapy or in conjuction with metformin to achieve and maintain optimal glycemic control.

Synthesis of DNA in oestrogen-induced pituitary tumurs in rats: effect of bromocriptine.

PubMed

Kalbermann, L E; Machiavelli, G A; De Nicola, A F; Weissenberg, L S; Burdman, J A

1980-11-01

Bromocriptine increased the concentration of prolactin in oestrogen-induced tumours of the rat pituitary gland. Prolactinaemia was significantly reduced and at the same time there was a considerable decrease in the weight of the tumour, in the incorporation of tritiated thymidine into DNA and in the activity of DNA polymerase alpha. The results suggested that the intracellular content of prolactin controls cell proliferation in this experimental tumour. A hypothalamic disorder is proposed as the primary cause of these tumours.

[Effect of total flavones from Cuscuta chinensis on expression of Fas/FasL, PCNA and HB-EGF in SD rats model with bromocriptine-induced abortion].

PubMed

Ma, Hong-Xia; You, Zhao-Ling; Wang, Xiao-Yun

2008-11-01

To explore the effect of total flavones from cuscuta chinensis (TFCC) on expression of Fas, PCNA and HB-EGF in SD rats model with bromocriptine-induced abortion. The model rats of bromocriptine during 6-8 d of pregnancy induced early abortion was established, adopting respectively herbs in high and low dosage and progesterone affect model rat and after 12 d, Immunohistochemical was applied to determine Fas, HB-EGF and PCNA in deciduas and placenta. Expression of PCNA on trophoblast and deciduas, HB-EGF on trophoblast, PR on deciduas in the model used Semen cuscutae flavonoid, proesterone and normal pregnacy, were significantlly higher than those of the pure model. Expression of Fas on trophoblast and deciduas in above four groups, were significantlly lower than those of the pure model. There were no expression of HB-EGF on deciduas. TFCC regulates the proliferation and apoptosis of the deciduas and cytotrophoblasts and prevents spontaneous abortions.

Quercetin improves postpartum hypogalactia in milk-deficient mice via stimulating prolactin production in pituitary gland.

PubMed

Lin, Man; Wang, Na; Yao, Bei; Zhong, Yao; Lin, Yan; You, Tianhui

2018-04-19

Postpartum dysgalactia is a common clinical problem for lactating women. Seeking out the safe and efficient phytoestrogens will be a promising strategy for postpartum dysgalactia therapy. In this study, the postpartum mice within four groups, including control group, the model group, and the treatment groups intragastrically administrated with normal saline, bromocriptine, bromocriptine plus 17α-ethinyl estradiol, and bromocriptine plus quercetin, respectively, were used. The results showed that quercetin, a kind of natural phytoestrogen, could efficiently promote lactation yield and mammary gland development in the agalactosis mice produced by bromocriptine administration. Mechanically, quercetin, such as 17α-ethinyl estradiol, significantly stimulated prolactin (PRL) production and deposition in the mammary gland in the agalactosis mice determined by western blotting, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Furthermore, quercetin could increase the expression of β-casein, stearoyl-CoA desaturase, fatty acid synthase, and α-lactalbumin in the breast tissues that are responsible for the production of fatty acid, lactose, and galactose in the milk at the transcriptional level determined by quantitative polymerase chain reaction. Specifically, quercetin promoted primary mammary epithelial cell proliferation and stimulated prolactin receptor (PRLR) expression probably via AKT activation in vitro. In conclusion, this study indicates that estrogen-like quercetin promotes mammary gland development and lactation yield in milk-deficient mice, probably via stimulating PRL expression and release from the pituitary gland, as well as induces PRLR expression in primary mammary epithelial cells. Copyright © 2018 John Wiley & Sons, Ltd.

Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice.

PubMed

Bilic, I; Zoricic, I; Anic, T; Separovic, J; Stancic-Rokotov, D; Mikus, D; Buljat, G; Ivankovic, D; Aralica, G; Prkacin, I; Perovic, D; Mise, S; Rotkvic, I; Petek, M; Rucman, R; Seiwerth, S; Sikiric, P

2001-03-09

The focus was on haloperidol (central dopamine antagonist)-stomach lesion, a longly described suitable counterpart of dopamine blocker cysteamine-duodenal lesion. In this, the contribution of blockade of central/peripheral dopamine receptors and prostaglandins synthesis, along with influence of antiulcer agents was evaluated in mice. Male NMRI Hannnover mice were sacrificed 24 h after haloperidol (25 mg/kg b.w. i.p., given alone or with saline (haloperidol+saline) (i) or in combination (ii,iii)). Supporting central dopamine predominance for haloperidol stomach lesion induction, co-administration of peripheral dopamine receptor antagonist domperidone (5 mg/kg i.p.) (haloperidol+ domperidone) (ii), or prostaglandin synthesis inhibitor indomethacin (10 mg/kg s.c.) (haloperidol+ indomethacin) (iii) did not aggravate this lesion. (i) In haloperidol+saline challenged mice the lesions were inhibited by co-administration (/kg i.p.) of a gastric pentadecapeptide BPC 157, GlyGluProProProGlyLysProAlaAspAspAlaGlyLeuVal, M.W. 1419 (10 microg, 10 ng, 10 pg, but not 1 pg, 100 fg, 10 fg), bromocriptine (10 mg), omeprazole (10 mg, 100 mg, but not 1 mg). Atropine (10, 100, 200 mg), pirenzepine (10, 100, 200 mg), misoprostol (10, 100, 200 microg), pantoprazole (1, 10, 100 mg), lansoprazole (0.1, 1, 10 mg), cimetidine (10, 100, 200 mg) and ranitidine (10, 100, 200 mg) were not effective. (ii) Dopamine peripheral blockade influence: in haloperidol+domperidone mice, previously effective bromocriptine, pentadecapeptide BPC 157 (10 microg) or omeprazole (10 mg) did not attenuate stomach lesions. (iii) Prostaglandins synthesis blockade effect: in haloperidol+indomethacin mice, previously effective agents, bromocriptine or omeprazole were not active, while BPC 157 effect was only lessened.

The effects of Vitex agnus castus extract and its interaction with dopaminergic system on LH and testosterone in male mice.

PubMed

Nasri, Sima; Oryan, Shahrbano; Rohani, Ali Haeri; Amin, Gholam Reza

2007-07-15

The purpose of this study was to evaluate the probable effects of Vitex agnus castus (Vac.) on the male reproductive physiology. It is a well known fact that LH secretion from the anterior pituitary of mammals is controlled by many neurotransmiters such as dopamine. In this experiment, we have studied the effect of Vac. extract on the LH and testosterone hormones and its interaction with the dopaminergic system on male mice. In order to evaluate these effects, we used the hydroalcoholic Vac. extract (for extraction we used percolation technique) injection with the following doses: 65, 165, 265, 365 and 465 mg kg-', bromocriptine as a dopamine receptor agonist (5, 10, 20 mg kg(-1)) and haloperidol as a dopamine receptor antagonist (1, 1.5, 2, 2.5, 3 mg kg(-1)). To study the interaction between Vac. extract and dopaminergic system, we injected the optimum doses of Vac. with bromocriptine or haloperidol at the same time. Intraperitoneal injections were applied in all experiments, once a day for 30 days. The control group remained intact and the sham group received vehicle. After the last injection, we collected the animal blood serums for hormonal assays. LH and testosterone were measured by Radio Immuno Assay (RIA). LH and testosterone, showed significant decrease in bromocriptine group and haloperidol increased these hormones. Vac. extract decreased significantly the LH and testosterone levels. The coadministration of Vac. extract and bromocriptine decreased LH and testosterone. Coadministration of Vac. extract and haloperidol decreased LH and testosterone levels. These results suggest: dopamine regulates the gonadotroph-leydig cells axis. It appears that Vac. exertes effects through dopaminergic system and other pathways. The findings of this study show we can use Vac. extract for pathological cases of increasing LH and testosterone.

The Synergistic Effect of Raloxifene, Fluoxetine, and Bromocriptine Protects Against Pilocarpine-Induced Status Epilepticus and Temporal Lobe Epilepsy.

PubMed

Pottoo, Faheem Hyder; Tabassum, Nahida; Javed, Md Noushad; Nigar, Shah; Rasheed, Rouqia; Khan, Ayash; Barkat, Md Abul; Alam, Md Sabir; Maqbool, Amir; Ansari, Mohammad Azam; Barreto, George E; Ashraf, Ghulam Md

2018-06-07

The present antiepileptic drugs pose several problems in the management of seizures owing to their meager neuroprotective potential, adverse effects on bone, detrimental effects on cognitive function, chronic toxicity, drug interactions, side effects including aggression, agitation, and irritability and sometimes exacerbation of seizures. We followed up progressive preclinical investigation in mice against pilocarpine (PILO)-induced status epilepticus (SE) and temporal lobe epilepsy (TLE). To determine the response of raloxifene (RF) (4 and 8 mg/kg), fluoxetine (FT) (14 and 22 mg/kg), bromocriptine (BC) (6 and 10 mg/kg), and their low-dose combinations, oral treatment was scheduled for 28 days followed by PILO (300 mg/kg, i.p). The response was stalked for intensive behavioral monitoring of convulsions, hippocampal neuropeptide Y (NPY), and oxidative stress discernment along with histomorphological studies. The resultant data confirmed the therapeutic potential of triple drug combination of raloxifene (4 mg/kg) with fluoxetine (14 mg/kg) and bromocriptine (6 mg/kg) compared to monotherapy with raloxifene (4 mg/kg), and bromocriptine (6 mg/kg) as otherwise monotherapy with fluoxetine (14 mg/kg) was ineffective to suppress convulsions; an effect better than sodium valproate (300 mg/kg), a standard AED, was validated. Most profoundly, PILO-induced compensatory increases in hippocampal NPY levels (20.01%), which was escalated (100%) with the triple drug combination. The same pattern of results was superseded for oxidative stress indices and neuronal damage. The results for the first time demonstrate the propitious role of triple drug combination in the management of SE and TLE. Therapeutically, this enhancing profile of drugs fosters a safer and more effective drug-combination regimen. Graphical abstract ᅟ.

The long-term effects of megavoltage radiotherapy as sole or combined therapy for large prolactinomas: studies with high definition computerized tomography.

PubMed

Johnston, D G; Hall, K; Kendall-Taylor, P; Ross, W M; Crombie, A L; Cook, D B; Watson, M J

1986-06-01

The long-term sequelae of external pituitary irradiation alone or in combination with surgery and/or bromocriptine therapy have been studied in 14 patients with large prolactinomas over an observation period of 6-22 years (mean 13 years). Galactorrhoea was abolished in four of the five females with this symptom, but menstrual disturbance persisted in five of six patients. Sexual function was normal without sex hormone replacement in only one of the eight males after treatment. Neurological deficits were abolished or improved by treatment in all 9 patients with this presentation. Serum prolactin levels declined after treatment (P less than 0.001) and fell to within the normal range off bromocriptine therapy in six of the 14 patients at a mean of 9 years (range 5-17 years) after radiotherapy. All patients had anterior pituitary deficiency of some degree at reassessment, and 13 required replacement treatment. Serial skull radiographs revealed remineralization of the fossa floor in five patients and a decrease in fossa size in three. All five patients who did not also have surgery had evidence of tumour shrinkage without bromocriptine treatment (on CT scan or metrizamide cisternography). Fourth generation CT scans on completion of the study revealed a decrease in tumour mass in all patients, with varying degrees of empty sella in 13 and a cystic intrasellar tumour in the remaining one. Residual tumour was demonstrated in 10 patients, three of whom had normal serum prolactin levels, while one patient without visible tumour had persistent hyperprolactinaemia. Radiotherapy, alone or in combination with surgery and bromocriptine, effectively decreases prolactin secretion and tumour size in patients with large prolactinomas at the expense of other anterior pituitary function. Circulating prolactin levels are a poor marker of residual tumour volume.

Prosocial effects of prolactin in male rats: Social recognition, social approach and social learning.

PubMed

Donhoffner, Mary E; Al Saleh, Samar; Schink, Olivia; Wood, Ruth I

2017-11-01

Prolactin (PRL) and oxytocin (OT) are pituitary hormones essential for lactation, but also promote sexual behavior. OT stimulates social behaviors, such as recognition, approach, and learning, but less is known about PRL in these behaviors. Since PRL and OT have complementary functions in reproduction, we hypothesized that PRL increases social recognition, approach, and learning. Male Long-Evans rats received ovine PRL (oPRL; 0.5, 2.0 or 5.0mg/kg), the PRL antagonist bromocriptine (0.1, 3.0 or 5.0mg/kg) or saline 20 mins before testing for recognition of familiar vs. unfamiliar stimulus males. Saline controls preferred the unfamiliar male (p<0.05), while bromocriptine blocked this preference. oPRL did not increase preference. To measure social approach, we determined if PRL restores approach 2h after defeat by an aggressive male. Defeated rats avoided the aggressive male. 2mg/kg oPRL, before or after defeat, restored approach towards the aggressive male (p<0.05). In non-defeated rats, oPRL or 3mg/kg bromocriptine had no effect. To determine if PRL increases social learning, we tested social transmission of food preference. Rats choose between two unfamiliar flavors, one of which they have previously been exposed to through interaction with a demonstrator rat. Vehicle controls preferred chow with the demonstrated flavor over the novel flavor. oPRL-treated rats were similar. Bromocriptine-treated rats failed to show a preference. When tested one week later, only oPRL-treated rats preferred the demonstrated flavor. The results suggest that PRL is required for social recognition and learning, and that increasing PRL enhances social memory and approach, similar to OT. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of dopaminergic modulation on electrophysiological brain response to affective stimuli.

PubMed

Franken, Ingmar H A; Nijs, Ilse; Pepplinkhuizen, Lolke

2008-01-01

Several theoretical accounts of the role of dopamine suggest that dopamine has an influence on the processing of affective stimuli. There is some indirect evidence for this from studies showing an association between the treatment with dopaminergic agents and self-reported affect. We addressed this issue directly by examining the electrophysiological correlates of affective picture processing during a single-dose treatment with a dopamine D2 agonist (bromocriptine), a dopamine D2 antagonist (haloperidol), and a placebo. We compared early and late event-related brain potentials (ERPs) that have been associated with affective processing in the three medication treatment conditions in a randomized double-blind crossover design amongst healthy males. In each treatment condition, subjects attentively watched neutral, pleasant, and unpleasant pictures while ERPs were recorded. Results indicate that neither bromocriptine nor haloperidol has a selective effect on electrophysiological indices of affective processing. In concordance with this, no effects of dopaminergic modulation on self-reported positive or negative affect was observed. In contrast, bromocriptine decreased overall processing of all stimulus categories regardless of their affective content. The results indicate that dopaminergic D2 receptors do not seem to play a crucial role in the selective processing of affective visual stimuli.

The Medical Treatment of New-Onset Peripartum Cardiomyopathy: A Systematic Review of Prospective Studies.

PubMed

Desplantie, Olivier; Tremblay-Gravel, Maxime; Avram, Robert; Marquis-Gravel, Guillaume; Ducharme, Anique; Jolicoeur, E Marc

2015-12-01

Peripartum cardiomyopathy (PPCM) is a rare disorder with potentially fatal consequences, which occurs mainly in previously healthy women. The aetiology of PPCM remains unknown and various pathologic mechanisms have been proposed, including immune-mediated injuries and impaired response to oxidative stress and inflammatory cytokines. Several therapies have been studied, but few have been validated in a well-designed randomized controlled trial. In the present study we sought to review the medical treatment intended for acute PPCM. To this end, we performed a systematic review of the literature of randomized and nonrandomized prospective clinical studies. We identified 2 randomized controlled trials that evaluated the dopamine agonist bromocriptine and the inotrope levosimendan, respectively, and 1 nonrandomized study that evaluated the nonselective phosphodiesterase inhibitor pentoxifylline. We reviewed the pathophysiological, pharmacological, and clinical properties for each treatment option identified. Bromocriptine and pentoxifylline both improved left ventricular systolic function and patient-oriented clinical end points and levosimendan did not improve mortality or echocardiographic findings of PPCM. In this review we identified bromocriptine and pentoxifylline, but not levosimendan, as potentially useful agents to improve left ventricle function and outcomes in PPCM. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Comparison of the Efficacy of Different Drugs on Non-Motor Symptoms of Parkinson's Disease: a Network Meta-Analysis.

PubMed

Li, Bao-Dong; Cui, Jing-Jun; Song, Jia; Qi, Ce; Ma, Pei-Feng; Wang, Ya-Rong; Bai, Jing

2018-01-01

A network meta-analysis is used to compare the efficacy of ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, for non-motor symptoms in Parkinson's disease (PD). PubMed, Embase and the Cochrane Library were searched from their establishment dates up to January 2017 for randomized controlled trials (RCTs) investigating the efficacy of the above ten drugs on the non-motor symptoms of PD. A network meta-analysis combined the evidence from direct comparisons and indirect comparisons and evaluated the pooled weighted mean difference (WMD) values and surfaces under the cumulative ranking curves (SUCRA). The network meta-analysis included 21 RCTs. The analysis results indicated that, using the United Parkinson's Disease Rating Scale (UPDRS) III, the efficacies of placebo, ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole and levodopa in treating PD were lower than that of apomorphine (WMD = -10.90, 95% CI = -16.12∼-5.48; WMD = -11.85, 95% CI = -17.31∼-6.16; WMD = -11.15, 95% CI = -16.64∼-5.04; WMD = -11.70, 95% CI = -16.98∼-5.60; WMD = -11.04, 95% CI = -16.97∼-5.34; WMD = -13.27, 95% CI = -19.22∼-7.40; WMD = -10.25, 95% CI = -15.66∼-4.32; and WMD = -11.60, 95% CI = -17.89∼-5.57, respectively). Treatment with ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil or levodopa, with placebo as a control, on PD exhibited no significant differences on PD symptoms when the UPDRS II was used for evaluation. Moreover, using the UPDRS III, the SUCRA values indicated that a pomorphine had the best efficacy on the non-motor symptoms of PD (99.0%). Using the UPDRS II, the SUCRA values for ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil and levodopa treatments, with placebo as a control, indicated that bromocriptine showed the best efficacy on the non-motor symptoms of PD (75.6%). Among ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, apomorphine may be the most efficacious drug for therapy in treating the non-motor symptoms of PD. © 2018 The Author(s). Published by S. Karger AG, Basel.

Hyperthyroidism and acromegaly due to a thyrotropin- and growth hormone-secreting pituitary tumor. Lack of hormonal response to bromocriptine.

PubMed

Carlson, H E; Linfoot, J A; Braunstein, G D; Kovacs, K; Young, R T

1983-05-01

A 47-year-old woman with acromegaly and hyperthyroidism was found to have an inappropriately normal serum thyrotropin level (1.5 to 2.5 microU/ml) that responded poorly to thyrotropin-releasing hormone but showed partial responsiveness to changes in circulating thyroid hormones. Serum alpha-subunit levels were high-normal and showed a normal response to thyrotropin-releasing hormone. Growth hormone and thyrotropin hypersecretion persisted despite radiotherapy and bromocriptine treatment. Selective trans-sphenoidal removal of a pituitary adenoma led to normalization of both growth hormone and thyrotropin levels. Both thyrotropes and somatotropes were demonstrated in the adenoma by the immunoperoxidase technique and electron microscopy.

Bromocriptine

MedlinePlus

... that prevents you from digesting foods containing sugar, starch, or dairy products normally.tell your doctor if ... drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To ...

Sensitive method for the quantitative determination of bromocriptine in human plasma by liquid chromatography-tandem mass spectrometry.

PubMed

Salvador, Arnaud; Dubreuil, Didier; Denouel, Jannick; Millerioux, L

2005-06-25

A sensitive LC-MS-MS assay for the quantitative determination of bromocriptine has been developed and validated and is described in this work. The assay involved the extraction of the analyte from 1 ml of human plasma using a solid phase extraction on Oasis MCX cartridges. Chromatography was performed on a Symmetry C18 (2.1 mm x 100 mm, 3.5 microm) column using a mobile phase consisting of 25:75:01 acetonitrile-water-formic acid with a flow rate of 250 microl/min. The linearity was within the concentration range of 2-500 pg/ml. The lower limit of quantification was 2 pg/ml. This method has been demonstrated to be an improvement over existing methods due to its greater sensitivity and specificity.

Tolcapone: new drug. In Parkinson's disease: unacceptable risk of severe hepatitis.

PubMed

2006-04-01

(1) When patients with Parkinson's disease who are taking levodopa develop motor fluctuations that do not respond to dose adjustments, the standard treatment is the addition of bromocriptine, a dopaminergic agonist. Evaluation of entacapone fails to show whether the risk-benefit balance of this catechol-O-methyltransferase (COMT) inhibitor is at least as favourable as that of bromocriptine. (2) Tolcapone, another COMT inhibitor, is back on the French market after being withdrawn because of serious hepatic effects. The summary of product characteristics (SPC) specifies that tolcapone must only be used when entacapone treatment fails or is poorly tolerated. (3) Renewal of marketing authorisation was based on one clinical trial in which about half the patients were probably not resistant to entacapone. No difference in efficacy was found between tolcapone and entacapone. There is no firm evidence that tolcapone is effective in a significant number of patients in whom entacapone fails. (4) Placebo-controlled trials show that first-line treatment with tolcapone 100 mg to 200 mg 3 times a day reduces the duration of motor freezing ("off") periods, but the global impact of tolcapone on parkinsonism appears to be limited. (5) Unblinded randomised controlled trials have failed to show that tolcapone is more effective than bromocriptine or pergolide. There are no trials assessing the use of tolcapone in combination with dopamine agonists. (6) Adverse effects were frequent during clinical trials. They were mainly neurological and gastrointestinal, and differed from those associated with bromocriptine. In 1988, shortly after worldwide marketing of tolcapone, 3 cases of fatal fulminant hepatitis were reported among about 60 000 patients who had taken this drug. Some countries, including European Union member states, withdrew marketing authorisation. Other countries, including the United States, left tolcapone on the market but required stringent monitoring of liver function. Due to a lack of transparency on the part of both the manufacturer and the health authorities, we do not know if these measures reduced the risk of severe hepatitis. In the trial versus entacapone, one of the 75 patients treated with tolcapone 300 mg/day had an abnormal increase in serum transaminase activity. (7) In practice, tolcapone has a negative risk-benefit balance.

Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes.

PubMed

Newman-Tancredi, Adrian; Cussac, Didier; Quentric, Yann; Touzard, Manuelle; Verrièle, Laurence; Carpentier, Nathalie; Millan, Mark J

2002-11-01

Although certain antiparkinson agents interact with serotonin (5-HT) receptors, little information is available concerning functional actions. Herein, we characterized efficacies of apomorphine, bromocriptine, cabergoline, lisuride, piribedil, pergolide, roxindole, and terguride at human (h)5-HT(1A), h5-HT(1B), and h5-HT(1D) receptors [guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding], and at h5-HT(2A), h5-HT(2B), and h5-HT(2C) receptors (depletion of membrane-bound [(3)H]phosphatydilinositol). All drugs stimulated h5-HT(1A) receptors with efficacies (compared with 5-HT, 100%) ranging from modest (apomorphine, 35%) to high (cabergoline, 93%). At h5-HT(1B) receptors, efficacies varied from mild (terguride, 37%) to marked (cabergoline, 102%) and potencies were modest (pEC(50) values of 5.8-7.6): h5-HT(1D) sites were activated with a similar range of efficacies and greater potency (7.1-8.5). Piribedil and apomorphine were inactive at h5-HT(1B) and h5-HT(1D) receptors. At h5-HT(2A) receptors, terguride, lisuride, bromocriptine, cabergoline, and pergolide displayed potent (7.6-8.8) agonist properties (49-103%), whereas apomorphine and roxindole were antagonists and piribedil was inactive. Only pergolide (113%/8.2) and cabergoline (123%/8.6) displayed pronounced agonist properties at h5-HT(2B) receptors. At 5-HT(2C) receptors, lisuride, bromocriptine, pergolide, and cabergoline were efficacious (75-96%) agonists, apomorphine and terguride were antagonists, and piribedil was inactive. MDL100,907 and SB242,084, selective antagonists at 5-HT(2A) and 5-HT(2C) receptors, respectively, abolished these actions of pergolide, cabergoline, and bromocriptine. In conclusion, antiparkinson agents display markedly different patterns of agonist and antagonist properties at multiple 5-HT receptor subtypes. Although all show modest (agonist) activity at 5-HT(1A) sites, their contrasting actions at 5-HT(2A) and 5-HT(2C) sites may be of particular significance to their functional profiles in vivo.

Effect of dopamine-related drugs on duodenal ulcer induced by cysteamine or propionitrile: prevention and aggravation may not be mediated by gastrointestinal secretory changes in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gallagher, G.; Brown, A.; Szabo, S.

1987-03-01

Dose- and time-response studies have been performed with dopamine agonists and antagonists using the cysteamine and propionitrile duodenal ulcer models in the rat. The experiments demonstrate that the chemically induced duodenal ulcer is prevented by bromocriptine, lergotrile and reduced by apomorphine or L-dopa. Aggravation of cysteamine-induced duodenal ulcer was seen especially after (-)-butaclamol, (-)-sulpiride, haloperidol and, less effectively, after other dopaminergic antagonists. The duodenal antiulcerogenic action of dopamine agonists was more prominent after chronic administration than after a single dose, whereas the opposite was found concerning the proulcerogenic effect of dopamine antagonists. In the chronic gastric fistula rat, both themore » antiulcerogens bromocriptine or lergotrile and the proulcerogens haloperidol, pimozide or (-)-N-(2-chlorethyl)-norapomorphine decreased the cysteamine- or propionitrile-induced gastric secretion. No correlation was apparent between the influence of these drugs on duodenal ulcer development and gastric and duodenal (pancreatic/biliary) secretions. In the chronic duodenal fistula rat, decreased acid content was measured in the proximal duodenum after haloperidol, and diminished duodenal pepsin exposure was recorded after bromocriptine. Furthermore, the aggravation by dopamine antagonists of experimental duodenal ulcer probably involves a peripheral component. The site of dopamine receptors and physiologic effects which modulate experimental duodenal ulcer remain to be identified, but their elucidation may prove to be an important element in the pathogenesis and treatment of duodenal ulcer.« less

Hyperprolactinaemia: analysis of presentation, diagnosis and treatment in the endocrine service of a general hospital.

PubMed

Suliman, A M; al-saber, F; Hayes, F; Fiad, T; Culliton, M; Cunningham, S; McKenna, T J

2000-05-01

The charts of 184 patients with clinically significant hyperprolactinaemia who presented to a teaching hospital between 1978-1995 were reviewed, 158 (86%) females and 26 (14%) males. Hyperprolactinaemia was due to a microadenoma or was idiopathic in 36.4%, drug induced in 16%, associated with a macroadenoma in 12%, due to epilepsy in 7%, with other causes each contributing 5% or less. The presenting symptoms were amenorrhoea in 64%, galactorrhoea in 40.5%, infertility in 15%, visual field defect in 9%, with impotence in 30% and, gynaecomastia in 8% of men. One hundred and one patients were treated with bromocriptine (80%), surgery (35.4%) and radiotherapy (10.7%). Twenty-five percent of patients developed side-effects of bromocriptine for which cabergoline, a new long-lasting dopaminergic agonist, was successfully substituted. Presenting features responded to drug treatment in 70-80% of patients.

[Psychosomatic aspects of stress].

PubMed

Okuse, S; Anzai, T

1992-03-01

We established the Bromocriptine test for the dopaminergic function of the hypothalamopituitary gland. The secretion patterns of plasma GH and PRL to 2.5 mg Bromocriptine, a dopamine receptor agonist, were classified into two types; a response type and a non-response type. The former showed an increase in plasma GH levels and suppression of PRL secretion; the latter showed no change in GH after Bromocriptine administration. The response type cases corresponded to psychosocial stress by neurotic and maladaptive behavior. The non-response type cases corresponded to psychosocial stress by alexithymic and over adaptive behaviors. Case Presentation 1. Essential Hypertension: a. 56-year old male, response type, blood pressure elevated by stress in daily life. Psychosomatic treatment: advice about blood pressure measurement at his home, brief psychotherapy and drug therapy. b. 53-year-old male, non-response type, type A behavior. Psychosomatic treatment: advice to increase awareness of body-mind relationships of his disorder, self-control training and drug therapy. 2. Gastric ulcers: a. 40-year-old male, response type, CMI IV region (Neurotic tendencies). Psychosomatic treatment: autogenic training and drug therapy. b. 28-year-old male, non-response type, high JAS scores(Over adaptative behavior). Psychosomatic treatment: advice to increase awareness of body-mind relationships of occurrence of his ulcers, to induce change in his perceptions of way of life, to encourage taking rest. 3. Technostress syndrome: a. 23-year-old female, response type, technoanxiety. Psychosomatic treatment: advice to make her take rest, and change in arrangements at her working place. b. 27-year-old male, non-response type, technodependent. Psychosomatic treatment: Fasting therapy. This therapy changed the non-response pattern to normal.

Working memory span capacity improved by a D2 but not D1 receptor family agonist.

PubMed

Tarantino, Isadore S; Sharp, Richard F; Geyer, Mark A; Meves, Jessica M; Young, Jared W

2011-06-01

Patients with schizophrenia exhibit poor working memory (WM). Although several subcomponents of WM can be measured, evidence suggests the primary subcomponent affected in schizophrenia is span capacity (WMC). Indeed, the NIMH-funded MATRICS initiative recommended assaying the WMC when assessing the efficacy of a putative therapeutic for FDA approval. Although dopamine D1 receptor agonists improve delay-dependent memory in animals, evidence for improvements in WMC due to dopamine D1 receptor activation is limited. In contrast, the dopamine D2-family agonist bromocriptine improves WMC in humans. The radial arm maze (RAM) can be used to assess WMC, although complications due to ceiling effects or strategy confounds have limited its use. We describe a 12-arm RAM protocol designed to assess whether the dopamine D1-family agonist SKF 38393 (0, 1, 3, and 10 mg/kg) or bromocriptine (0, 1, 3, and 10 mg/kg) could improve WMC in C57BL/6N mice (n=12) in cross-over designs. WMC increased and strategy usage decreased with training. The dopamine D1 agonist SKF 38393 had no effect on WMC or long-term memory. Bromocriptine decreased WMC errors, without affecting long-term memory, consistent with human studies. These data confirm that WMC can be measured in mice and reveal drug effects that are consistent with reported effects in humans. Future research is warranted to identify the subtype of the D2-family of receptors responsible for the observed improvement in WMC. Finally, this RAM procedure may prove useful in developing animal models of deficient WMC to further assess putative treatments for the cognitive deficits in schizophrenia. Copyright © 2011 Elsevier B.V. All rights reserved.

Curcumin (Diferuloylmethane) Inhibits Cell Proliferation, Induces Apoptosis, and Decreases Hormone Levels and Secretion in Pituitary Tumor Cells

PubMed Central

Miller, Matthew; Chen, Shenglin; Woodliff, Jeffrey; Kansra, Sanjay

2008-01-01

Prolactinomas are the most prevalent functional pituitary adenomas. Dopamine D2 receptor (D2R) agonists, such as bromocriptine are the first line of therapy; however, drug intolerance/resistance to D2R agonists exists. Apart from D2R agonists, there is no established medical therapy for prolactinomas; therefore, identifying novel therapeutics is warranted. Curcumin, a commonly used food additive in South Asian cooking, inhibits proliferation of several tumor cell lines; however, its effect on pituitary tumor cell proliferation has not been determined. Our objectives were to: 1) determine whether curcumin inhibits proliferation of pituitary tumor cell lines; 2) identify the signaling intermediaries that mediate the effect of curcumin; 3) examine whether curcumin inhibited pituitary hormone production and release; and 4) examine whether curcumin could enhance the growth-inhibitory effect of bromocriptine. Using rat lactotroph cell lines, GH3 and MMQ cells, we report that curcumin had a robust dose and time-dependent inhibitory effect on GH3 and MMQ cell proliferation. Inhibitory effects of curcumin persisted, even on removal of curcumin, and curcumin also blocked colony formation ability of pituitary tumor cells. The growth-inhibitory effect of curcumin was accompanied by decreased expression of cyclin D3 and ser 780 phosphorylation of retinoblastoma protein. In addition, curcumin also induced apoptosis in both GH3 and MMQ cells. Furthermore, curcumin suppresses intracellular levels and release of both prolactin and GH. Finally, we show that low concentrations of curcumin enhanced the growth-inhibitory effect of bromocriptine on MMQ cell proliferation. Taken together we demonstrate that curcumin inhibits pituitary tumor cell proliferation, induces apoptosis, and decreases hormone production and release, and thus, we propose developing curcumin as a novel therapeutic tool in the management of prolactinomas. PMID:18450960

Curcumin (diferuloylmethane) inhibits cell proliferation, induces apoptosis, and decreases hormone levels and secretion in pituitary tumor cells.

PubMed

Miller, Matthew; Chen, Shenglin; Woodliff, Jeffrey; Kansra, Sanjay

2008-08-01

Prolactinomas are the most prevalent functional pituitary adenomas. Dopamine D2 receptor (D2R) agonists, such as bromocriptine are the first line of therapy; however, drug intolerance/resistance to D2R agonists exists. Apart from D2R agonists, there is no established medical therapy for prolactinomas; therefore, identifying novel therapeutics is warranted. Curcumin, a commonly used food additive in South Asian cooking, inhibits proliferation of several tumor cell lines; however, its effect on pituitary tumor cell proliferation has not been determined. Our objectives were to: 1) determine whether curcumin inhibits proliferation of pituitary tumor cell lines; 2) identify the signaling intermediaries that mediate the effect of curcumin; 3) examine whether curcumin inhibited pituitary hormone production and release; and 4) examine whether curcumin could enhance the growth-inhibitory effect of bromocriptine. Using rat lactotroph cell lines, GH3 and MMQ cells, we report that curcumin had a robust dose and time-dependent inhibitory effect on GH3 and MMQ cell proliferation. Inhibitory effects of curcumin persisted, even on removal of curcumin, and curcumin also blocked colony formation ability of pituitary tumor cells. The growth-inhibitory effect of curcumin was accompanied by decreased expression of cyclin D3 and ser 780 phosphorylation of retinoblastoma protein. In addition, curcumin also induced apoptosis in both GH3 and MMQ cells. Furthermore, curcumin suppresses intracellular levels and release of both prolactin and GH. Finally, we show that low concentrations of curcumin enhanced the growth-inhibitory effect of bromocriptine on MMQ cell proliferation. Taken together we demonstrate that curcumin inhibits pituitary tumor cell proliferation, induces apoptosis, and decreases hormone production and release, and thus, we propose developing curcumin as a novel therapeutic tool in the management of prolactinomas.

Polycystic ovary syndrome and prolactinoma association.

PubMed

Yavasoglu, Irfan; Kucuk, Mert; Coskun, Adil; Guney, Engin; Kadikoylu, Gurhan; Bolaman, Zahit

2009-01-01

Hyperprolactinemia is the most common pituitary hormone hypersecretion syndrome in both men and women. Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting 5%-10% of reproductive age women. Here, we present a patient with irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia who was diagnosed as PCOS and prolactinoma and admitted to our clinic. Prolactinoma and PCOS association is a rare condition. This 33-year-old woman was admitted to the internal medicine outpatient clinic for irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia. Her laboratory results were as follows: prolactin was 74 ng/mL (normal range:1.8-20.3 ng/mL). Pelvic ultrasonography was correlated with polycystic ovary syndrome. Pituitary MRI showed 6x8 mm microadenoma at left half. Bromocriptine was started with 1.25 mg/day and increased to 5 mg/day. After six months of bromocriptine treatment her prolactin level was normal and no adenoma was detected in pituitary MRI. PCOS and prolactinoma association should be taken into account in PCOS cases with mild hyperprolactinoma.

Hypothyroidism Affects D2 Receptor-mediated Breathing without altering D2 Receptor Expression

PubMed Central

Schlenker, Evelyn H.; Rio, Rodrigo Del; Schultz, Harold D.

2015-01-01

Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age- matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a peripheral D2 receptor agonist), increased oxygen consumption and body temperature in awake air-exposed hypothyroid female hamsters and stimulated their ventilation before and following exposure to hypoxia. Carmoxirole depressed frequency of breathing in euthyroid hamsters prior to, during and following hypoxia exposures and stimulated it in the hypothyroid hamsters following hypoxia. Although hypothyroidism did not affect expression of D2 receptors, it influenced central D2 modulation of breathing in a disparate manner relative to euthyroid hamsters. PMID:24434437

Hypothyroidism affects D2 receptor-mediated breathing without altering D2 receptor expression.

PubMed

Schlenker, Evelyn H; Del Rio, Rodrigo; Schultz, Harold D

2014-03-01

Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age-matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a peripheral D2 receptor agonist), increased oxygen consumption and body temperature in awake air-exposed hypothyroid female hamsters and stimulated their ventilation before and following exposure to hypoxia. Carmoxirole depressed frequency of breathing in euthyroid hamsters prior to, during and following hypoxia exposures and stimulated it in the hypothyroid hamsters following hypoxia. Although hypothyroidism did not affect expression of D2 receptors, it influenced central D2 modulation of breathing in a disparate manner relative to euthyroid hamsters. Copyright © 2014 Elsevier B.V. All rights reserved.

Vanishing tumor in pregnancy

PubMed Central

Vimal, M. V.; Budyal, Sweta; Kasliwal, Rajeev; Jagtap, Varsha S.; Lila, Anurag R.; Bandgar, Tushar; Menon, Padmavathy; Shah, Nalini S.

2012-01-01

A patient with microprolactinoma, who had two successful pregnancies, is described for management issues. First pregnancy was uneventful. During the second pregnancy, the tumor enlarged to macroprolactinoma with headache and blurring of vision which was managed successfully with bromocriptine. Post delivery, complete disappearance of the tumor was documented. PMID:23226664

Pentadecapeptide BPC 157 interactions with adrenergic and dopaminergic systems in mucosal protection in stress.

PubMed

Sikirić, P; Mazul, B; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Jurina, L; Konjevoda, P; Hanzevacki, M; Gjurasin, M; Separović, J; Ljubanović, D; Artuković, B; Bratulić, M; Tisljar, M; Miklić, P; Sumajstorcić, J

1997-03-01

Since superior protection against different gastrointestinal and liver lesions and antiinflammatory and analgesic activities were noted for pentadecapeptide BPC (an essential fragment of an organoprotective gastric juice protein named BPC), the beneficial mechanism of BPC 157 and its likely interactions with other systems were studied. Hence its beneficial effects would be abolished by adrenal gland medullectomy, the influence of different agents affecting alpha, beta, and dopamine receptors on BPC 157 gastroprotection in 48 h restraint stress was further investigated. Animals were pretreated (1 hr before stress) with saline (controls) or BPC 157 (dissolved in saline) (10 microg or 10 ng/kg body wt intraperitoneally or intragastrically) applied either alone to establish basal conditions or, when manipulating the adrenergic or dopaminergic system, a simultaneous administration was carried out with various agents with specific effects on adrenergic or dopaminergic receptors [given in milligrams per kilogram intraperitoneally except for atenolol, which was given subcutaneously] phentolamine (10.0), prazosin (0.5), yohimbine (5.0), clonidine (0.1) (alpha-adrenergic domain), propranolol (1.0), atenolol (20.0) (beta-adrenergic domain), domperidone (5.0), and haloperidol (5.0) (peripheral/central dopamine system). Alternatively, agents stimulating adrenergic or dopaminergic systems--adrenaline (5.0) or bromocriptine (10.0)--were applied. A strong protection, noted following intragastric or intraperitoneal administration of BPC 157, was fully abolished by coadministration of phentolamine, clonidine, and haloperidol, and consistently not affected by prazosin, yohimbine, or domperidone. Atenolol abolished only intraperitoneal BPC 157 protection, whereas propranolol affected specifically intragastric BPC 157 protection. Interestingly, the severe course of lesion development obtained in basal conditions, unlike BPC 157 gastroprotection, was not influenced by the application of these agents. In other experiments, when adrenaline and bromocriptine were given simultaneously, a strong reduction of lesion development was noted. However, when applied separately, only adrenaline, not bromocriptine, has a protective effect. Thus, a complex protective interaction with both alpha-adrenergic (eg, catecholamine release) and dopaminergic (central) systems could be suggested for both intragastric and intraperitoneal BPC 157 administration. The involvement of beta-receptor stimulation in BPC 157 gastroprotection appears to be related to the route of BPC 157 administration. The demonstration that a combined stimulation of adrenergic and dopaminergic systems by simultaneous prophylactic application of adrenaline (alpha- and beta-receptor stimulant) and bromocriptine (dopamine receptor agonist) may significantly reduce restraint stress lesions development provides insight for further research on the beneficial mechanism of BPC 157.

Pharmacotherapy of Aphasia: Myth or Reality?

ERIC Educational Resources Information Center

de Boissezon, Xavier; Peran, Patrice; de Boysson, Chloe; Demonet, Jean-Francois

2007-01-01

Pharmacotherapy of aphasia had been discussed for the last twenty years with first bromocriptine and amphetamine and then serotoninergic, GABAergic and cholinergic agents. Here, we reviewed the MEDLINE available reports of drug therapy for aphasia. So far, proofs of efficiency were found indubitable for none of the studied molecules. However, some…

THE NEUROLEPTIC MALIGNANT SYNDROME : REPORT OF THREE CASES

PubMed Central

Sharma, R.C.; Thakur, S.; Sharma, Vijay

1996-01-01

Three patients, one male and two females who developed neuroleptic malignant syndrome following exposure to depot and oral neuroleptic are presented. The patients satisfied Levenson′s criteria for diagnosis. Bromocriptine and Electro Convulsive Therapy were found effective whereas trihexyphenidyl proved unsatisfactory in the treatment. All the patients recovered completely without complications. PMID:21584154

Ergopeptines bromocriptine and ergovaline and the dopamine type-2 receptor inhibitor domperidone inhibit bovine equilibrative nucleoside transporter 1-like activity

USDA-ARS?s Scientific Manuscript database

Forages infected with Neotyphodium coenophialum produce ergot alkaloids that alter the systemic physiology of cattle such that reproduction, lactation, and growth are decreased. Ergopeptines are one predominant class of ergot alkaloids. However, aside from their interactions with biogenic amine rece...

[Parkinson therapy 1985].

PubMed

Kaeser, H E

1986-06-14

The problems of long term treatment with antiparkinson drugs are numerous, involving increased involuntary movements, painful dystonic cramps, decrease or loss of therapeutic benefit, wearing-off, episodes of akinesia (on-off) and long periods of "freezing". Important side effects are also mental changes with heavy dreams, hallucinations, nocturnal confusional states and paranoid psychosis. As most of these side effects are dose-related, they are postponed and lessened by small daily doses of L-dopa and decarboxylase inhibitor. Frequent small doses may decrease the wearing-off effect but may cause unpredictable episodes of on-off. The addition of or partial replacement by bromocriptine may decrease fluctuations and dyskinesias in many patients. To reduce the side effects such as nausea, orthostatic hypotension and mental disturbances, daily doses of 15-30 mg should be built up very slowly. Painful dystonias are related to the off period and respond well to baclofen. For the treatment of severe psychic disturbances tranquilizers with little or no extrapyramidal side effects, such as clomethiazole, benzodiazepine derivatives and (if necessary) thioridazine, are recommended. Bromocriptine may also be useful in occasional cases which do not, or no longer, respond to L-dopa.

Kidnapping of chicks in emperor penguins: a hormonal by-product?

PubMed

Angelier, Frédéric; Barbraud, Christophe; Lormée, Hervé; Prud'homme, François; Chastel, Olivier

2006-04-01

The function and causes of kidnapping juveniles are little understood because individuals sustain some breeding costs to rear an unrelated offspring. Here we focus on the proximal causes of this behaviour in emperor penguins (Aptenodytes forsteri), whose failed breeders often kidnap chicks. We experimentally tested the hypothesis that kidnapping behaviour was the result of high residual levels of prolactin (PRL), a hormone involved in parental behaviour. Penguins with artificially decreased PRL levels by bromocriptine administration kidnapped chicks less often than control penguins. Within the bromocriptine treated group, kidnapping behaviour was not totally suppressed and the probability of kidnapping a chick was positively correlated to PRL levels measured before treatment. During breeding, emperor penguins have to forage in remote ice-free areas. In these birds, PRL secretion is poorly influenced by chick stimuli and has probably evolved to maintain a willingness to return to the colony after a long absence at sea. Therefore, penguins that have lost their chick during a foraging trip still maintain high residual PRL levels and this, combined with colonial breeding, probably facilitates kidnapping. We suggest that kidnapping in non-cooperative systems may result from a hormonal byproduct of a reproductive adaptation to extreme conditions.

[Breast-feeding (part II): Lactation inhibition--Guidelines for clinical practice].

PubMed

Marcellin, L; Chantry, A A

2015-12-01

Provide guidelines for clinical use of non-pharmacological and pharmacological treatments of inhibition of lactation and the management of the weaning. Systematically review of the literature between 1972 and May 2015 from the databases Medline, Google Scholar, Cochrane Library, and the international recommendations about inhibition of lactation with establishment of levels of evidence (LE) and grades of recommendation. The available data on the effectiveness of non-pharmacological measures are limited, with very low levels of evidence that fail to make recommendations (Professional consensus). Pharmacological treatments for inhibition of lactation should not be given routinely to women who do not wish to breast-feed (Professional consensus). For women aware of the risks of pharmacological treatments of inhibition of lactation, lisuride and cabergolin are the preferred drugs (Professional consensus). Because of potentially serious adverse effects, bromocriptin is contraindicated in inhibiting lactation (Professional consensus). Available data on management of lactation weaning fail to provide recommendation and no treatment is recommended (Professional consensus). Bromocriptin is contraindicated in the treatment of inhibiting lactation. Women who do not wish to breast-feed have to be informed of the benefits and disadvantages of the pharmacological treatment for inhibition of lactation. Copyright © 2015. Published by Elsevier Masson SAS.

[Juvenile Parkinson's disease and recurring prematurity. Case report].

PubMed

Ha, D-E; Legendre, G; Colau, J-C

2007-03-01

The association of Parkinson's disease and pregnancy is very rare. Some thirty cases are found in the literature. We report the case of a pregnancy in a 30-year-old patient with juvenile Parkinson's disease. During this pregnancy treated by levodopa and bromocriptine, no aggravation of the symptoms was been observed. However, the pregnancy was complicated by a premature delivery at 31 weeks of amenorrhoea.

Pituitary tumour causing gigantism. Morphology and in vitro hormone secretion.

PubMed

Anniko, M; Ritzén, E M

1986-01-01

True gigantism with overproduction of growth hormone (GH) and prolactin (PRL) was diagnosed in a 13-year-old boy. The clinical history indicated that the tumour had caused an oversecretion of GH since the age of 4-5 years. At diagnosis, the sella turcica was markedly enlarged. No infiltrative growth was noted at surgery. Endocrine investigations showed elevated GH and PRL secretion. Light and electron microscopy of tumour tissue revealed densely packed pleomorphic cells of both GH and PRL type. In addition, oncocyte-like cells were observed. Organ culture of pieces of tumour tissue demonstrated continued secretion of GH and PRL into the medium for more than 5 days in vitro. Addition of bromocriptine to the medium caused a rapid decline in PRL secretion while GH secretion remained the same. X-ray irradiation in vitro also caused a decrease in PRL secretion. These effects of bromocriptine and X-ray on hormone secretion in vitro mirrored the corresponding effect of treatment, when the patient showed signs of tumour recurrence after pituitary surgery. It is concluded that also in childhood, the in vitro response of tumour tissue to various treatments may be explored as a possible way to predict the efficacy of pharmacological or irradiation treatment of pituitary tumours.

A review of the efficacy and safety of oral antidiabetic drugs

PubMed Central

Stein, Stephanie Aleskow; Lamos, Elizabeth Mary; Davis, Stephen N

2014-01-01

Introduction Additional oral antidiabetic agents to metformin, sulfonylureas (SU) and thiazolidinediones (TZD) are approved for the treatment of type 2 diabetes. Areas covered The efficacy and safety of metformin, SUs, TZDs, dipeptidyl peptidase-IV (DPP-4) inhibitors, meglitinide analogs, α-glucosidase inhibitors (AGIs), bile-acid sequestrants (BAS) and bromocriptine will be reviewed. Expert opinion Several new oral agents have been approved for type 2 diabetes management in recent years. It is important to understand the efficacy and safety of these medications in addition to the older agents to best maximize oral drug therapy for diabetes. Of the recently introduced oral hypoglycemic/antihyperglycemic agents, the DPP-4 inhibitors are moderately efficacious compared with mainstay treatment with metformin with a low side-effect profile and have good efficacy in combination with other oral agents and insulin. They are a recommended alternative when metformin use is limited by gastrointestinal (GI) side effects or when SU treatment results in significant hypoglycemia or weight gain. Meglitinide analogs are limited by their frequent dosing, expense and hypoglycemia (repaglinide > nateglinide), while AGIs are also limited by their dosing schedule and GI side-effect profile. BAS and bromocriptine have the lowest efficacy with regard to HbA1c reduction, also are plagued by GI adverse reactions, but have a low risk of hypoglycemia. PMID:23241069

Neurogentics of Dopaminergic Receptor Super-sensitivity in Activation of Brain Reward Circuitry and Relapse: Proposing “Deprivation-Amplification Relapse Therapy” (DART)

PubMed Central

Downs, B. William; Bowirrat, Abdalla; Waite, Roger L.; Braverman, Eric R.; Madigan, Margaret; Oscar-Berman, Marlene; DiNubile, Nicholas; Gold, Mark

2013-01-01

Background and Hypothesis It is well known that after prolonged abstinence, individuals who imbibe or use their drug of choice experience a powerful euphoria that precipitates serious relapse. While a biological explanation for this conundrum has remained elusive, we hypothesize that this clinically observed “super sensitivity” might be tied to genetic dopaminergic polymorphisms. Another therapeutic conundrum relates to the paradoxical finding that the dopaminergic agonist bromocriptine induces stronger activation of brain reward circuitry in individuals who carry the DRD2 A1 allele compared to DRD2 A2 allele carriers. Based upon the fact that carriers of the A1 allele relative to the A2 allele of the DRD2 gene have significantly lower D2 receptor density, a reduced sensitivity to dopamine agonist activity would be expected in the former. Thus, it is perplexing that with low D2 density there is an increase in reward sensitivity with the dopamine agonist bromocriptine. Moreover, under chronic or long-term therapy, the potential proliferation of D2 receptors with bromocriptine has been shown in vitro. This seems to lead to a positive outcome and significantly better treatment compliance only in A1 carriers. Proposal and Conclusion We propose that low D2 receptor density and polymorphisms of the D2 gene are associated with risk for relapse of substance abuse including alcohol dependence, heroin craving, cocaine dependence, methamphetamine abuse, nicotine sensitization, and glucose craving. With this in mind, we suggest a putative physiological mechanism that may help to explain the enhanced sensitivity following intense acute dopaminergic D2 receptor activation: “denervation supersensitivity.” Thus, the administration of dopamine D2 agonists would target D2 sensitization and attenuate relapse, especially in D2 receptor A1 allele carriers. This hypothesized mechanism is supported by clinical trials utilizing the amino-acid neurotransmitter precursors, enkephalinase and catechol-O-methyl-transferase (COMT) enzyme inhibition, which have resulted in attenuated relapse rates in Reward Deficiency Syndrome (RDS) probands. Future warranted translational research with positive outcome showing prevented or lower relapse in RDS will ultimately support the proposed concept, which we term “Deprivation-Amplification Relapse Therapy (DART).” PMID:19940429

Management of prolactinomas.

PubMed

Molitch, M E

1989-01-01

Prolactinomas are the most common of the hormone-secreting pituitary tumors and must be distinguished from nonsecreting tumors causing hyperprolactinemia by hypothalamic or stalk dysfunction. For both micro- and macroadenomas, dopamine agonists appear to be the treatment of choice, transsphenoidal surgery being reserved for nonresponders. For women desiring pregnancy, dopamine agonists are safe when there is a microadenoma or an intrasellar macroadenoma. However, in women with large macroadenomas desiring pregnancy, limited transsphenoidal decompression followed by bromocriptine appears to be the safest mode of treatment.

Prolactin-Producing Pituitary Carcinoma, Hypopituitarism, and Graves' Disease-Report of a Challenging Case and Literature Review.

PubMed

Bettencourt-Silva, Rita; Pereira, Josué; Belo, Sandra; Magalhães, Daniela; Queirós, Joana; Carvalho, Davide

2018-01-01

The diagnosis of pituitary carcinoma is very rare, requires the evidence of metastatic disease, and has a poor overall survival. Malignant prolactinoma frequently requires dopamine agonist therapy, pituitary surgery, radiotherapy, and even chemotherapy. A 19-year-old female presented with galactorrhea, primary amenorrhea, and left hemianopsia. Complementary study detected hyperprolactinemia and a pituitary macroadenoma with cavernous sinus invasion and suprasellar growth. She was treated with cabergoline and bromocriptine without clinical or analytical improvement. Resection of the pituitary lesion was programmed and a non-contiguous lesion of the nasal mucosa was detected during the approach. This metastasis led to the diagnosis of prolactin-producing pituitary carcinoma. After partial resection, the patient was submitted to radiotherapy for residual disease with persistent symptoms. She developed growth hormone deficiency, central hypothyroidism, hypogonadism, and permanent diabetes insipidus. Six years later she was admitted for the suspicion of secondary adrenal insufficiency and thyrotoxicosis. Physical findings, laboratory data, thyroid ultrasound, and scintigraphy achieved the diagnosis of Graves' disease and hypocortisolism. She was treated with hydrocortisone and methimazole, but central hypothyroidism recurred after antithyroid drug withdrawal. Nine years after the diagnosis of a pituitary carcinoma, she maintains treatment with bromocriptine, has a locally stable disease, with no metastases. This report highlights an unusual presentation of a prolactin-producing pituitary carcinoma in a young female. The patient had multiple hormone deficiencies due to a pituitary lesion and treatments. The posterior development of hyperthyroidism and adrenal insufficiency brought an additional difficulty to the approach.

Select medications that unexpectedly lower HbA1c levels.

PubMed

Tillman, F; Kim, J

2018-04-19

A variety of medication classes are available for diabetes; however, treatment options become limited due to adverse effect profiles and cost. Current diabetes guidelines include agents not originally developed for diabetes treatment, bromocriptine and colesevelam. Other non-diabetes medications demonstrating haemoglobin A1c lowering, including agents for weight loss, depression, anaemia and coronary artery disease, are described in this review article. More research looking into the impact of non-diabetes medications on blood glucose may offer additional diabetes treatment strategies. © 2018 John Wiley & Sons Ltd.

Tuning the brain for motherhood: prolactin-like central signalling in virgin, pregnant, and lactating female mice.

PubMed

Salais-López, Hugo; Lanuza, Enrique; Agustín-Pavón, Carmen; Martínez-García, Fernando

2017-03-01

Prolactin is fundamental for the expression of maternal behaviour. In virgin female rats, prolactin administered upon steroid hormone priming accelerates the onset of maternal care. By contrast, the role of prolactin in mice maternal behaviour remains unclear. This study aims at characterizing central prolactin activity patterns in female mice and their variation through pregnancy and lactation. This was revealed by immunoreactivity of phosphorylated (active) signal transducer and activator of transcription 5 (pSTAT5-ir), a key molecule in the signalling cascade of prolactin receptors. We also evaluated non-hypophyseal lactogenic activity during pregnancy by administering bromocriptine, which suppresses hypophyseal prolactin release. Late-pregnant and lactating females showed significantly increased pSTAT5-ir resulting in a widespread pattern of immunostaining with minor variations between pregnant and lactating animals, which comprises nuclei of the sociosexual and maternal brain, including telencephalic (septum, nucleus of the stria terminalis, and amygdala), hypothalamic (preoptic, paraventricular, supraoptic, and ventromedial), and midbrain (periaqueductal grey) regions. During late pregnancy, this pattern was not affected by the administration of bromocriptine, suggesting it to be elicited mostly by non-hypophyseal lactogenic agents, likely placental lactogens. Virgin females displayed, instead, a variable pattern of pSTAT5-ir restricted to a subset of the brain nuclei labelled in pregnant and lactating mice. A hormonal substitution experiment confirmed that estradiol and progesterone contribute to the variability found in virgin females. Our results reflect how the shaping of the maternal brain takes place prior to parturition and suggest that lactogenic agents are important candidates in the development of maternal behaviours already during pregnancy.

The role of bromocriptine-QR in the management of type 2 diabetes expert panel recommendations.

PubMed

Garber, Alan J; Blonde, Lawrence; Bloomgarden, Zachary T; Handelsman, Yehuda; Dagogo-Jack, Samuel

2013-01-01

To review available data on the efficacy and safety of bromocriptine-QR (BQR) and to consider its role in the management of Type 2 diabetes mellitus (T2DM). Published literature reporting the efficacy and safety of BQR in the treatment of T2DM was reviewed, including peer-reviewed abstracts and poster presentations. BQR is an oral hypoglycemic agent with a novel mechanism of action that appears to involve enhancement of morning central nervous system (CNS) dopaminergic activity, resulting in improved insulin sensitivity and reduced hepatic glucose output. Adjunctive treatment with BQR in the dosing range of 1.6 to 4.8 mg/d may result in a mean (95% confidence interval [CI]) reduction in glycated hemoglobin (A1c) levels of 0.69% (0.97%, 0.41%). Treatment with BQR appears to be associated with minimal intrinsic risk of hypoglycemia, and does not appear to be associated with clinically significant adverse effects on weight, triglycerides, free fatty acids, or blood pressure. The favorable cardiovascular risk profile of BQR suggests that it may be useful in the treatment of patients with T2DM with a history of cardiovascular disease (CVD) or who have significant risk factors for CVD. However, knowledge of the efficacy and safety of BQR is limited by the relatively small clinical trials database. As a result, there is currently insufficient information on the safety and efficacy of adjunctive BQR in T2DM patients being treated with several common diabetes regimens (e.g., thiazolidinediones, insulin).

A case of multiple endocrine adenomatosis with primary amenorrhoea.

PubMed Central

Vandeweghe, M.; Braxel, K.; Schutyser, J.; Vermeulen, A.

1978-01-01

A well documented sporadic case of multiple endocrine adenomatosis (MEA) type I, with the pituitary tumour presenting as a prolactinoma, is described in a 28-year-old female. Primary amenorrhoea, resulting from hyperprolactinaemia, was the first symptom of the polyglandular neoplasia. A gastrinoma was removed from the head of the pancreas and latent hyperparathyroidism appeared to be present. Treatment with bromocriptine was poorly tolerated; neurosurgical intervention was refused by the patient. The possibility that a serum prolactin determination may be useful in detecting pituitary involvement in MEA deserves consideration. Images Fig. 1 Fig. 2 PMID:31610

Pentadecapeptide BPC 157, cimetidine, ranitidine, bromocriptine, and atropine effect in cysteamine lesions in totally gastrectromized rats: a model for cytoprotective studies.

PubMed

Sikirić, P; Mikus, D; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Perić, J; Konjevoda, P; Perović, D; Jurina, L; Hanzevacki, M; Separović, J; Gjurasin, M; Jadrijević, S; Jelovac, N; Miklić, P; Buljat, G; Marović, A

1997-05-01

A superior effectiveness in various lesion assays was noted for the novel pentadecapeptide BPC 157, originated from human gastric juice protein (BPC) and claimed to be a cytoprotective agent. From this viewpoint, as a previously untreated experimental improvement to create an acid-free environmental for cytoprotection studies, total gastrectomy was done 24 hr before the ulcerogenic procedure. In the absence of stomach and gastric acid, the damaging effects of cysteamine (400 mg/kg subcutaneously, death 24 hr thereafter), to date thought to be an acid-related duodenal ulcerogen, and the BPC 157 cytoprotective effect (10 microg or 10 ng/kg intraperitoneally) were further challenged. BPC 157 was compared with reference agents [cimetidine (50), ranitidine (10), omeprazole (10), bromocriptine (10) and atropine (10) (mg/kg intraperitoneally, 1 hr before cysteamine] known to be also cytoprotective. In naive rats, with intact stomach, all of them showed a strong beneficial effect. Interestingly, in gastrectomized animals, the application of BPC 157 or the reference agents before cysteamine significantly prevented the otherwise severe duodenal lesion development noted in the control gastrectomized cysteamine rats. In groups without cysteamine, no lesions were noted (laparotomy, gastrectomy only, 24 or 48 hr postsurgical period), nor was lesion potentiation seen in cysteamine-treated laparotomized animals. In summary, these findings--equal damaging effect of cysteamine and equal protection of pentadecapeptide BPC 157 and reference agents in gastrectomized and rats with intact stomach--seem to be particularly relevant for a cytoprotective viewpoint. Without a stomach, the cysteamine damaging effect was convincingly defined as an essential gastric acid-independent injury (analogous to ethanol gastric lesions). Likewise, a high "cytoprotective capacity," apparently acid independent, common for all tested agents (novel pentadecapeptide BPC 157, cimetidine, ranitidine, omeprazole and atropine) could be clearly stressed.

Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression

PubMed Central

Rana, Digvijay G.; Galani, Varsha J.

2014-01-01

Background: The effects of antidepressant treatments have traditionally been discussed primarily in terms of effects on noradrenergic and serotonergic systems. Multiple lines of investigation have also explored the role of dopaminergic systems in mental depression. Seed of Mucuna pruriens Linn. (DC) (Leguminoseae) is well-known with dopaminergic action and has several therapeutic applications in folk medicine in curing or managing a wide range of diseases including Parkinsonism. Aim: To elucidate the anti-depressent profile and possible dopaminergic modulating action of M. pruriens seeds in various experimental models of depression. Materials and Methods: In the present study, antidepressant effect of the hydroalcoholic extract of the M. pruriens seeds (MPE) (100 and 200 mg/kg, p.o.) was investigated in the Forced Swimming Test (FST), Tail Suspension Test (TST), and Chronic Unpredictable Mild Stress (CUMS) test in mice. Further, dopaminergic interaction of same doses of MPE in the FST and TST were checked by the administration of a haloperidol (0.1 mg/kg, i.p.) and bromocriptine (2 mg/kg, i.p.) on the 7th day of MPE treatment. Effect of MPE on locomotor activity was also checked using actophotometer. Results: MPE produced a significant reduction of the immobility time in the FST and TST. Further, antidepressant action of MPE was significantly inhibited by haloperidol and potentiated by bromocriptine in the FST and TST. 21 days of MPE treatment produced protection in CUMS as indicated by a significant increase of sucrose intake of stressed mice. Locomotor activities of mice were not significantly changed after 1 h and 7th day of the MPE treatment. Conclusion: The results of this study indicate that hydroalcoholic extract of MPE have antidepressant action, which may be mediated by an interaction with the dopaminergic system. PMID:25364207

Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression.

PubMed

Rana, Digvijay G; Galani, Varsha J

2014-01-01

The effects of antidepressant treatments have traditionally been discussed primarily in terms of effects on noradrenergic and serotonergic systems. Multiple lines of investigation have also explored the role of dopaminergic systems in mental depression. Seed of Mucuna pruriens Linn. (DC) (Leguminoseae) is well-known with dopaminergic action and has several therapeutic applications in folk medicine in curing or managing a wide range of diseases including Parkinsonism. To elucidate the anti-depressent profile and possible dopaminergic modulating action of M. pruriens seeds in various experimental models of depression. In the present study, antidepressant effect of the hydroalcoholic extract of the M. pruriens seeds (MPE) (100 and 200 mg/kg, p.o.) was investigated in the Forced Swimming Test (FST), Tail Suspension Test (TST), and Chronic Unpredictable Mild Stress (CUMS) test in mice. Further, dopaminergic interaction of same doses of MPE in the FST and TST were checked by the administration of a haloperidol (0.1 mg/kg, i.p.) and bromocriptine (2 mg/kg, i.p.) on the 7(th) day of MPE treatment. Effect of MPE on locomotor activity was also checked using actophotometer. MPE produced a significant reduction of the immobility time in the FST and TST. Further, antidepressant action of MPE was significantly inhibited by haloperidol and potentiated by bromocriptine in the FST and TST. 21 days of MPE treatment produced protection in CUMS as indicated by a significant increase of sucrose intake of stressed mice. Locomotor activities of mice were not significantly changed after 1 h and 7(th) day of the MPE treatment. The results of this study indicate that hydroalcoholic extract of MPE have antidepressant action, which may be mediated by an interaction with the dopaminergic system.

Copulation is reactivated by bromocriptine in male rats after reaching sexual satiety with a same sexual mate.

PubMed

Rojas-Hernández, Jorge; Juárez, Jorge

2015-11-01

Male sexual satiety has been associated with a decrease in dopamine levels. Spontaneous recovery of copulatory behavior begins at least 72 h after sexual satiety is reached or in the condition in which a sexually-satiated male is exposed to a new receptive female distinct from the one with which sexual satiety was reached. The aim of the present study was to explore whether dopaminergic activation by bromocriptine (BrCr) can reactivate copulatory behavior with the same sexual mate immediately after sexual satiety is reached. Male rats were divided into three groups exposed to one of the following three conditions: 1) administration of 2 mg/kgs.c. of BrCr and exposure to the same female with whom sexual satiety was previously reached; 2) administration of 0.3 mLs.c. of the vehicle solution with exposure to the same female with whom sexual satiety was reached; and, 3) exposure to a new receptive female after sexual satiety was reached. Results showed that BrCr significantly reactivated copulatory capability in sexually-satiated males with the same receptive female. In contrast, no males in the vehicle group ejaculated with the same female after reaching sexual exhaustion. Copulation was reactivated by BrCr in a way similar to that observed in untreated males exposed to a new receptive female (i.e., the Coolidge effect). The reversal of sexual satiety in the males treated with BrCr could be explained by its action on D2 family receptors, which promotes a reactivation of sexual motivation at a level sufficient to allow renewed copulation with the same female mate. Copyright © 2015 Elsevier Inc. All rights reserved.

Bromocriptine treatment at the end of lactation prevents hyperphagia, higher visceral fat and liver triglycerides in early-weaned rats at adulthood.

PubMed

Peixoto-Silva, Nayara; Moura, Egberto G; Carvalho, Janaine C; Nobre, Jéssica L; Quitete, Fernanda T; Pinheiro, Cintia R; Santos-Silva, Ana Paula; de Oliveira, Elaine; Lisboa, Patricia C

2017-04-01

Non-pharmacological early weaning (NPEW) leads offspring to obesity, higher liver oxidative stress and microsteatosis in adulthood. Pharmacological EW (PEW) by maternal treatment with bromocriptine (BRO) causes obesity in the adult progeny but precludes hepatic injury. To test the hypothesis that BRO prevents the deleterious changes of NPEW, we injected BRO into the pups from the NPEW model in late lactation. Lactating rats were divided into two groups: dams with an adhesive bandage around the body to prevent breastfeeding on the last 3 days of lactation and dams whose pups had free suckling (C). Offspring from both groups were subdivided into two groups: pups treated with BRO (intraperitoneal (i.p.) 4 mg/kg per day) on the last 3 days of lactation (NPEW/BRO and C/BRO) or pups treated with the vehicle (NPEW and C). At PN120, offspring were challenged with a high fat diet (HFD), and food intake was recorded after 30 minutes and 12 hours. Rats were killed at PN120 and PN200. At PN120, adipocyte size was greater in the NPEW group but was normal in the NPEW/BRO group. At PN200, the NPEW group presented hyperphagia, higher adiposity, adipocyte hypertrophy, hyperleptinaemia, glucose intolerance and increased hepatic triglycerides. These parameters were normalized in the NPEW/BRO group. In the feeding test, BRO groups showed lower HFD intake at 30 minutes than did their controls; however, at 12 hours, the NPEW group ate more HFD. The treatment with BRO can preclude some deleterious effects of the NPEW model, which prevented the development of overweight and its comorbidities. © 2017 John Wiley & Sons Australia, Ltd.

Bromocriptine tablet of self-microemulsifying system adsorbed onto porous carrier to stimulate lipoproteins secretion for brain cellular uptake.

PubMed

Thongrangsalit, Sirigul; Phaechamud, Thawatchai; Lipipun, Vimolmas; Ritthidej, Garnpimol C

2015-07-01

Both low solubility and high hepatic metabolism cause low oral bioavailability of bromocriptine mesylate (BM) leading to very low drug amount in brain. Self-microemulsion (SME) tablets were developed to improve solubility, stimulate lipoprotein synthesis to promote lymphatic transport, avoid hepatic metabolism and target drug to brain. SME liquid containing castor oil, Tween(®) 80 and Cremophor(®) EL was prepared and then adsorbed onto solid carries, Aerosil(®)200, Aeroperl(®)300 or NeusilinUS2(®), yielding SME powders. The optimal ratios of SME liquid to carriers determined from flowability and scanning electron photomicrographs before tableting were 1.5:1, 2:1 and 2.5:1 for Aerosil(®)200, Aeroperl(®)300 and NeusilinUS2(®), respectively. Only Aeroperl(®)300 SME tablet had comparable dissolution to BM commercial tablet. From in vitro study in Caco-2 cells, fluorescein loaded SME tablet showed higher uptake than fluorescein loaded in either oil or surfactant. Although significantly lower amount of drug was permeated from SME tablet than from commercial tablet, higher drug uptake was obviously observed (P<0.05). In addition, higher lipoprotein synthesis expressing as content of apolipoprotein B (apo-B) found in secreted chylomicron resulted in higher drug uptake in co-culture of brain endothelial cells (bEnd.3) and astrocytes (CTX TNA2) from drug loaded SME tablet when compared to commercial tablet (P<0.05) due to binding of apo-B to LDL receptors expressed on the surface of endothelial cells. Therefore, tablet of SME adsorbed onto porous carrier potentially delivered BM to brain via lymphatic transport by increasing the lipoprotein synthesis. Copyright © 2015. Published by Elsevier B.V.

Poststroke aphasia : epidemiology, pathophysiology and treatment.

PubMed

Berthier, Marcelo L

2005-01-01

Aphasia, the loss or impairment of language caused by brain damage, is one of the most devastating cognitive impairments of stroke. Aphasia is present in 21-38% of acute stroke patients and is associated with high short- and long-term morbidity, mortality and expenditure. Recovery from aphasia is possible even in severe cases. While speech-language therapy remains the mainstay treatment of aphasia, the effectiveness of conventional therapies has not been conclusively proved. This has motivated attempts to integrate knowledge from several domains in an effort to plan more rational therapies and to introduce other therapeutic strategies, including the use of intensive language therapy and pharmacological agents. Several placebo-controlled trials suggest that piracetam is effective in recovery from aphasia when started soon after the stroke, but its efficacy vanishes in patients with chronic aphasia. Drugs acting on catecholamine systems (bromocriptine, dexamfetamine) have shown varying degrees of efficacy in case series, open-label studies and placebo-controlled trials. Bromocriptine is useful in acute and chronic aphasias, but its beneficial action appears restricted to nonfluent aphasias with reduced initiation of spontaneous verbal messages. Dexamfetamine improves language function in subacute aphasia and the beneficial effect is maintained in the long term, but its use is restricted to highly selected samples. Pharmacological agents operating on the cholinergic system (e.g. donepezil) have shown promise. Data from single-case studies, case series and an open-label study suggest that donepezil may have beneficial effects on chronic poststroke aphasia. Preliminary evidence suggests that donepezil is well tolerated and its efficacy is maintained in the long term. Randomised controlled trials of donepezil and other cholinergic agents in poststroke aphasia are warranted.

Transient hyperprolactinemia in infertile women with luteal phase deficiency.

PubMed

Huang, K E; Bonfiglio, T A; Muechler, E K

1991-10-01

This study was conducted to evaluate the prevalence of transient hyperprolactinemia in infertile women with luteal phase deficiency. One hundred fifty-one luteal phase deficiency patients and 11 controls had serum prolactin (PRL) measured daily for 3-4 days near ovulation. Thirty-three subjects (21.9%) had transient hyperprolactinemia, with PRL above 20 ng/mL for 1 or 2 days, and were studied further. The blood samples of these 33 subjects and of the controls were also analyzed for LH and FSH. Plasma progesterone was measured on the fourth, seventh, and tenth days after ovulation in both groups. The mean (+/- SD) of the mid-cycle integrated LH surge (125.0 +/- 23.0 mIU/mL; N = 26) and the sum of three plasma progesterone levels (23.8 +/- 4.5 ng/mL; N = 21) in the luteal phase deficiency women were significantly (P less than .001) lower than those of the controls (LH 158.7 +/- 13.8 mIU/mL; progesterone 33.8 +/- 6.5 ng/mL). All 33 luteal phase deficiency subjects with transient hyperprolactinemia were treated with bromocriptine at a dose ranging from 1.25-5 mg/day to maintain mid-cycle PRL levels between 5-15 ng/mL. Both the integrated LH surge and the sum of three progesterone levels increased significantly (P less than .05) during bromocriptine treatment, to 142.6 +/- 22.4 mIU/mL (N = 20) and 28.2 +/- 6.2 ng/mL (N = 18), respectively. Fourteen of the 33 patients conceived. The cumulative probability of conception was 31% for six cycles and 45% for 12 cycles of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating breeding and pre-breeding prolactin and LH are not associated with clutch size in the zebra finch (Taeniopygia guttata).

PubMed

Ryan, Calen P; Dawson, Alistair; Sharp, Peter J; Meddle, Simone L; Williams, Tony D

2014-06-01

Clutch size is a fundamental predictor of avian fitness, widely-studied from evolutionary and ecological perspectives, but surprisingly little is known about the physiological mechanisms regulating clutch size variation. The only formal mechanistic hypothesis for avian clutch-size determination predicts an anti-gonadal effect of circulating prolactin (PRL) via the inhibition of luteinizing hormone (LH), and has become widely-accepted despite little experimental support. Here we investigated the relationship between pre-breeding and breeding plasma PRL and LH and clutch-size in captive-breeding female zebra finches (Taeniopygia guttata). Using a repeated-measures design, we followed individual females from pre-breeding, through multiple breeding attempts, and attempted to decrease PRL using the D2-receptor agonist, bromocriptine. Clutch size was independent of variation in pre-breeding PRL or LH, although pre-breeding LH was negatively correlated with the time between pairing and the onset of laying. Clutch size was independent of variation in plasma PRL on all days of egg-laying. Bromocriptine treatment had no effect on plasma PRL, but in this breeding attempt clutch size was also independent of plasma PRL. Finally, we found no evidence for an inverse relationship between plasma PRL and LH levels, as predicted if PRL had inhibitory effects via LH. Thus, our data fail to provide any support for the involvement of circulating PRL in clutch size determination. These findings suggest that alternative models for hormonal control of avian clutch size need to be considered, perhaps involving downstream regulation of plasma PRL at the level of the ovary, or other hormones that have not been considered to date. Copyright © 2014 Elsevier Inc. All rights reserved.

Contraceptive choices for women with endocrine complications.

PubMed

Loriaux, D L; Wild, R A

1993-06-01

Previous confusion regarding the interference by oral contraceptives in measurements of endocrine function have been largely eliminated by the advent of improved, more sensitive assays. There are few if any contraindications to oral contraceptive use in patients with thyroid disease. Patients with prolactinoma can be treated with bromocriptine to restore fertility and prevent mineral loss. However, as a less expensive alternative, oral contraceptives can be prescribed to correct mineral loss, because there is no convincing evidence of an adverse effect on prolactinomas by the steroidal content of the pill. Oral contraceptives comprise a near ideal treatment modality for women with polycystic ovary disease because, among other effects, oral contraceptives reduce synthesis of androgen by inhibiting pituitary gonadotropin secretion.

Novel therapies for the management of type 2 diabetes mellitus: part 1. pramlintide and bromocriptine-QR.

PubMed

Grunberger, George

2013-06-01

Several classes of antidiabetic agents have been introduced into the market place over the past dozen years. As our understanding of the underlying pathophysiology of type 2 diabetes has advanced, attempts have been made to address these defects specifically. This brief review focuses on our experience with two such pharmacological approaches: (i) a synthetic amylin analog addressing amylin deficiency; and (ii) a dopaminergic agonist, focused on enhancing the lowered dopaminergic tone in patients with type 2 diabetes. Importantly, the use of these agents is not associated with hypoglycemia or weight gain. © 2013 Wiley Publishing Asia Pty Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

Hyperthyroidism caused by a pituitary thyrotrophin-secreting tumour with excessive secretion of thyrotrophin-releasing hormone and subsequently followed by Graves' disease in a middle-aged woman.

PubMed

Kamoi, K; Mitsuma, T; Sato, H; Yokoyama, M; Washiyama, K; Tanaka, R; Arai, O; Takasu, N; Yamada, T

1985-11-01

A 46-year-old woman had signs of thyrotoxicosis and galactorrhoea. Serum immunoreactive TSH and its alpha-subunit increased in the presence of high serum triiodothyronine (T3), thyroxine (T4), and free T4 concentrations, whereas beta-subunit TSH was undetectable. Exogenous TRH failed to increase serum TSH. Serum TSH was markedly suppressed by glucocorticoid, but was increased by antithyroid drug. L-Dopa or bromocriptine partially suppressed, but nomifensine had no influence on serum TSH. Serum prolactin (Prl) was above normal and markedly increased by TRH, but depressed by bromocriptine and not suppressed by nomifensine. Plasma TRH was normal in the hyperthyroid state, but was increased by glucocorticoid and antithyroid drug. Excess thyroid hormone depressed plasma TRH concentrations. Basal serum GH levels were constantly low. Transsphenoidal removal of the tumour normalized serum hormones (T3, T4 free T4, TSH, alpha-subunit and Prl), and eradicated the clinical signs of hyperthyroidism and galactorrhoea. Histological study of the tumour tissue demonstrated both thyrotrophes and somatotrophes. A reciprocal relationship between serum TSH and T4 concentrations shifted to a higher level before but was normalized after removal of the tumour. Ten months later, the clinical signs of thyrotoxicosis and the increase in serum thyroid hormone recurred without a concomitant increase in serum TSH and its alpha-subunit. Thyroidal auto-antibodies were slightly positive, but thyrotrophin-binding inhibitor immunoglobulin (TBII) was negative. Administration of antithyroid drug produced a euthyroid state, but 3 years later, discontinuation of the treatment resulted in recurrent hyperthyroidism without suppressed plasma TRH and with no evidence of regrowth of the pituitary tumour. It is suggested that the patient initially had hyperthyroidism owing to excessive TSH secretion from the tumour caused by abnormal TRH secretion, and subsequently had hyperthyroidism owing to Graves' disease.

Divergent long-term consequences of chronic treatment with haloperidol, risperidone, and bromocriptine on traumatic brain injury-induced cognitive deficits.

PubMed

Phelps, Thomas I; Bondi, Corina O; Ahmed, Rashid H; Olugbade, Yewande T; Kline, Anthony E

2015-04-15

Antipsychotic drugs (APDs) are provided in the clinic to manage traumatic brain injury (TBI)-induced agitation and aggression. Experimental TBI studies consistently show that daily administration of the APDs, haloperidol (HAL) and risperidone (RISP), hinder recovery. However, it is unknown how long the adverse effects remain after cessation of treatment. To elucidate this clinically relevant issue, anesthetized male rats were randomly assigned to four TBI (controlled cortical impact) and four sham groups administered HAL (0.5 mg/kg), RISP (0.45 mg/kg), bromocriptine (BRO; 5.0 mg/kg, included as a control for D2 receptor action), or vehicle (VEH; 1 mL/kg) 24 h after surgery and once-daily for 19 days. Motor and cognitive recovery was assessed on days 1-5 and 14-19, respectively, and again at 1 and 3 months after drug withdrawal. No overall group differences were observed for motor function among the TBI groups, although the HAL group showed a greater beam-walk deficit on day 5 versus the VEH and BRO groups. Cognitive recovery was significantly impaired in the HAL and RISP groups during the treatment phase versus VEH and BRO. Further, BRO was superior to VEH (p=0.0042). At 1 month, both groups that received APDs continued to exhibit significant cognitive impairment versus VEH and BRO; at 3 months, only the HAL group was impaired. Moreover, the HAL, RISP, and VEH groups continued to be cognitively deficient versus BRO, which also reduced cortical damage. These data replicate previous reports that HAL and RISP impede cognitive recovery after TBI and expand the literature by revealing that the deleterious effects persist for 3 months after drug discontinuation. BRO conferred cognitive benefits when administered concomitantly with behavioral testing, thus replicating previous findings, and also after cessation demonstrating enduring efficacy.

Phenotyping and outcome on contemporary management in a German cohort of patients with peripartum cardiomyopathy.

PubMed

Haghikia, A; Podewski, E; Libhaber, E; Labidi, S; Fischer, D; Roentgen, P; Tsikas, D; Jordan, J; Lichtinghagen, R; von Kaisenberg, C S; Struman, I; Bovy, N; Sliwa, K; Bauersachs, J; Hilfiker-Kleiner, Denise

2013-07-01

Peripartum cardiomyopathy (PPCM) is a life-threatening heart disease developing towards the end of pregnancy or in the months following delivery in previously healthy women in terms of cardiac disease. Enhanced oxidative stress and the subsequent cleavage of the nursing hormone Prolactin into an anti-angiogenic 16 kDa subfragment emerged as a potential causal factor of the disease. We established a prospective registry with confirmed PPCM present in 115 patients (mean baseline left ventricular ejection fraction, LVEF: 27 ± 9 %). Follow-up data (6 ± 3 months) showed LVEF improvement in 85 % and full recovery in 47 % while 15 % failed to recover with death in 2 % of patients. A positive family history of cardiomyopathy was present in 16.5 %. Pregnancy-associated hypertension was associated with a better outcome while a baseline LVEF ≤ 25 % was associated with a worse outcome. A high recovery rate (96 %) was observed in patients obtaining combination therapy with beta-blocker, angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor-blockers (ARBs) and bromocriptine. Increased serum levels of Cathepsin D, the enzyme that generates 16 kDa Prolactin, miR-146a, a direct target of 16 kDa Prolactin, N-terminal-pro-brain-natriuretic peptide (NT-proBNP) and asymmetric dimethylarginine (ADMA) emerged as biomarkers for PPCM. In conclusion, low baseline LVEF is a predictor for poor outcome while pregnancy-induced hypertensive disorders are associated with a better outcome in this European PPCM cohort. The high recovery rate in this collective is associated with a treatment concept using beta-blockers, ACE inhibitors/ARBs and bromocriptine. Increased levels of Cathepsin D activity, miR-146a and ADMA in serum of PPCM patients support the pathophysiological role of 16 kDa Prolactin for PPCM and may be used as a specific diagnostic marker profile.

Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thanos, P.K.; Wang, G.; Thanos, P.K.

Dopamine (DA) and DAD{sub 2} receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and amore » progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation.« less

Comparison of the functional potencies of ropinirole and other dopamine receptor agonists at human D2(long), D3 and D4.4 receptors expressed in Chinese hamster ovary cells

PubMed Central

Coldwell, Martyn C; Boyfield, Izzy; Brown, Tony; Hagan, Jim J; Middlemiss, Derek N

1999-01-01

The aim of the present study was to characterize functional responses to ropinirole, its major metabolites in man (SKF-104557 (4-[2-(propylamino)ethyl]-2-(3H) indolone), SKF-97930 (4-carboxy-2-(3H) indolone)) and other dopamine receptor agonists at human dopamine D2(long) (hD2), D3 (hD3) and D4.4 (hD4) receptors separately expressed in Chinese hamster ovary cells using microphysiometry.All the receptor agonists tested (ropinirole, SKF-104557, SKF-97930, bromocriptine, lisuride, pergolide, pramipexole, talipexole, dopamine) increased extracellular acidification rate in Chinese hamster ovary clones expressing the human D2, D3 or D4 receptor. The pEC50s of ropinirole at hD2, hD3 and hD4 receptors were 7.4, 8.4 and 6.8, respectively. Ropinirole is therefore at least 10 fold selective for the human dopamine D3 receptor over the other D2 receptor family members.At the hD2 and hD3 dopamine receptors all the compounds tested were full agonists as compared to quinpirole. Talipexole and the ropinirole metabolite, SKF-104557, were partial agonists at the hD4 receptor.Bromocriptine and lisuride had a slow onset of agonist action which precluded determination of EC50s.The rank order of agonist potencies was dissimilar to the rank order of radioligand binding affinities at each of the dopamine receptor subtypes. Functional selectivities of the dopamine receptor agonists, as measured in the microphysiometer, were less than radioligand binding selectivities.The results show that ropinirole is a full agonist at human D2, D3 and D4 dopamine receptors. SKF-104557 the major human metabolite of ropinirole, had similar radioligand binding affinities to, but lower functional potencies than, the parent compound. PMID:10455328

The history of ergot of rye (Claviceps purpurea) III: 1940-80.

PubMed

Lee, M R

2010-03-01

The period 1940-80 in the history of ergot was dominated by two investigators, Arthur Stoll and Albert Hofmann. There was great excitement when their group isolated from ergot preparations the powerful psychotropic agent lysergic acid diethylamide (LSD). It was thought that this substance would help to find the cause of schizophrenia and other psychotic disorders, but it would prove to be a great disappointment and Hofmann would say later, in private, that he regretted having spent so much time on the compound. By contrast, bromocriptine, derived from ergocriptine, would prove a pivotal substance in our knowledge of dopamine receptors in the central nervous system. It is widely used for the suppression of lactation, the treatment of prolactinomas and the management of Parkinson's disease.

Neuroleptic malignant syndrome: case report and discussion

PubMed Central

Chandran, Geethan J.; Mikler, John R.; Keegan, David L.

2003-01-01

WE REPORT A CASE INVOLVING AN 81-YEAR-OLD man with schizoaffective disorder who presented with neuroleptic malignant syndrome (NMS) after an increase in his neuroleptic dose. NMS, a rare but potentially fatal complication of neuroleptic medications (e.g., antipsychotics, sedatives and antinauseants), is characterized by hyperthermia, muscle rigidity, an elevated creatine kinase level and autonomic instability. The syndrome often develops after a sudden increase in dosage of the neuroleptic medication or in states of dehydration. Treatment is mainly supportive and includes withdrawal of the neuroleptic medication and, possibly, administration of drugs such as dantrolene and bromocriptine. Complications of NMS include acute renal failure and acute respiratory failure. Given the widespread prescription of neuroleptics by physicians in a variety of fields, all physicians need to be able to recognize and appropriately manage NMS. PMID:12952806

Stress and fertility: some modalities of investigation and treatment in couples with unexplained infertility in Dublin.

PubMed

Harrison, R F; O'Moore, R R; O'Moore, A M

1986-01-01

The role of stress in infertility, and its treatment, is reviewed in various groups of couples labeled "unexplained infertile." A simplified profile of stress markers based upon basal prolactin estimations and psychological measurements found infertile couples more stressed than fertile controls and revealed a sub-group of women characterized as having significantly high psychological stress scores and intermittent elevations of prolactin (spikers). This group was effectively treated with a combination of clomiphene citrate and bromocriptine. However, attention to the failures as well as the successes suggests optimum benefit to the patients might involve not only provision of a good clinic ambiance and pharmacological preparations, but also relaxation therapies such as Autogenic Training, which significantly lowered psychological and biochemical stress marker scores.

Impact of bromocriptine-QR therapy on cardiovascular outcomes in type 2 diabetes mellitus subjects on metformin.

PubMed

Chamarthi, Bindu; Ezrokhi, Michael; Rutty, Dean; Cincotta, Anthony H

2016-11-01

Type 2 diabetes mellitus (T2DM) is associated with a substantially increased risk of cardiovascular disease (CVD). Bromocriptine-QR (B-QR), a quick release sympatholytic dopamine D 2 receptor agonist, is a FDA-approved therapy for T2DM which may provide CVD risk reduction. Metformin is considered to be an agent with a potential cardioprotective benefit. This large placebo controlled clinical study assessed the impact of B-QR addition to existing metformin therapy on CVD outcomes in T2DM subjects. 1791 subjects (1208 B-QR; 583 placebo) on metformin ± another anti-diabetes therapy at baseline derived from the Cycloset Safety Trial, a 12-month, randomized, multicenter, placebo-controlled, double-blind study in T2DM, were included in this study. The primary CVD endpoint evaluated was treatment impact on CVD event rate, prespecified as a composite of time to first myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina/congestive heart failure. Impact on glycemic control was evaluated as a secondary analysis. The composite CVD end point occurred in 16/1208 B-QR treated (1.3%) and 18/583 placebo treated (3.1%) subjects resulting in a 55% CVD hazard risk reduction (intention-to-treat, Cox regression analysis; HR: 0.45 [0.23-0.88], p = 0.028). Kaplan-Meier curves demonstrated a significantly lower cumulative incidence rate of the CVD endpoint in the B-QR treatment group (Log-Rank p = 0.017). In subjects with poor glycemic control (HbA1c ≥ 7.5) at baseline, B-QR therapy relative to placebo resulted in a significant mean %HbA1c reduction of -0.59 at week 12 and -0.51 at week 52 respectively (p < 0.001 for both) and a 10 fold higher percent of subjects achieving HbA1c goal of ≤7% by week 52 (B-QR 30%, placebo 3%; p = 0.003). These findings suggest that in T2DM subjects on metformin, BQR therapy may represent an effective strategy for reducing CVD risk. Cycloset Safety Trial registration: ClinicalTrials.gov Identifier: NCT00377676.

[Vitex Agnus Castus in the treatment of hyperprolactinemia and menstrual disorders - a case report].

PubMed

Męczekalski, Błażej; Czyżyk, Adam

2015-07-01

We describe a patient with mild hyperprolactinemia and menstrual disorders (oligomenorrhea). She presented relative hypoestrogenism in laboratory tests. Magnetic resonans excluded the presence of pituitary adenoma. Because patient developed a bromocriptine intolerance, the Vitex Agnus Castus (VAC) extract has been introduced. The VAC therapy was effective, with symptoms relief and improvement of hormonal tests. The VAC medicines are indicated for the treatment of premenstrual syndrome (PMS), mastalgia, menstrual disorders and mild hyperprolactinemia. The mechanism of action is not fully understood, but it is related to dopaniergic activity of diterpenes and castacin in VAC. The randomized clinical trials revealed efficacy of VAC extract in the treatmet of hyperprolactinemia, menstrual disorders, PMS and mastalgia. Good tolerability, lack of serious side-effects and drug interactions are the advantages of the VAC preparations. © 2015 MEDPRESS.

Development of a Rapid Insulin Assay by Homogenous Time-Resolved Fluorescence

PubMed Central

Vallaghe, Julie; Gregor, Nathalie; Donthamsetti, Prashant; Harris, Paul E.; Pierre, Nicolas; Freyberg, Robin; Charrier-Savournin, Fabienne; Javitch, Jonathan A.; Freyberg, Zachary

2016-01-01

Direct measurement of insulin is critical for basic and clinical studies of insulin secretion. However, current methods are expensive and time-consuming. We developed an insulin assay based on homogenous time-resolved fluorescence that is significantly more rapid and cost-effective than current commonly used approaches. This assay was applied effectively to an insulin secreting cell line, INS-1E cells, as well as pancreatic islets, allowing us to validate the assay by elucidating mechanisms by which dopamine regulates insulin release. We found that dopamine functioned as a significant negative modulator of glucose-stimulated insulin secretion. Further, we showed that bromocriptine, a known dopamine D2/D3 receptor agonist and newly approved drug used for treatment of type II diabetes mellitus, also decreased glucose-stimulated insulin secretion in islets to levels comparable to those caused by dopamine treatment. PMID:26849707

[Hypertension and pregnancy: Post-partum period].

PubMed

Hugon-Rodin, Justine; Plu-Bureau, Geneviève

2016-01-01

Post-partum period is associated with specific characteristics in women with gestational disorders or preeclampsia. For breastfeeding women, the choice of antihypertensive treatment should take into account the impact on child health. The impact of breastfeeding on health mother must be also discussed. Moreover, for lactation inhibition, bromocriptine should not be used, especially in the context of gestational disorders. In post-partum period, the best contraceptive strategy is only-progestin contraception or non-hormonal contraceptives use. However, this choice will depend on the stabilization or normalization of blood pressure in early post-partum period. Finally, several consultations should be suggested: an information and announcement to explain the consequences of these gestational disorders and organize their multidisciplinary management and follow-up. A preconceptional consultation takes its place to anticipate potential recurrent preeclampsia or gestational hypertension and to schedule a future pregnancy in optimal conditions. Copyright © 2016. Published by Elsevier Masson SAS.

Sex and Gender Differences in Myocarditis and Dilated Cardiomyopathy

PubMed Central

Fairweather, DeLisa; Cooper, Leslie T; Blauwet, Lori A

2014-01-01

Heart failure due to nonischemic dilated cardiomyopathy (DCM) contributes significantly to the global burden of cardiovascular disease. Myocarditis is in turn a major cause of acute dilated cardiomyopathy in both men and women. However, recent clinical and experimental evidence suggests that the pathogenesis and prognosis of DCM differ between the sexes. This seminar provides a contemporary perspective on the immune mediators of myocarditis, including interdependent elements of the innate and adaptive immune response. The heart's acute response to injury is influenced by sex hormones that appear to determine the subsequent risk of chronic DCM. Preliminary data suggest additional genetic variations may account for some of the differences in epidemiology, left ventricular recovery and survival between men and women. We highlight the gaps in our knowledge regarding the management of women with acute DCM and discuss emerging therapies, including bromocriptine for the treatment of peripartum cardiomyopathy. PMID:23158412

Hyperthyroidism due to inappropriate secretion of thyroid-stimulating hormone: diagnosis and management.

PubMed

Hermus, A; Ross, H; van Liessum, P; Naber, A; Smals, A; Kloppenborg, P

1991-06-01

The case histories of three patients with hyperthyroidism due to overproduction of thyroid-stimulating hormone (TSH) by the pituitary gland are described. In the first patient treatment with the T3-metabolite 3,5,3'-triiodothyroacetic acid (TRIAC) led to complete clinical and biochemical normalization. In the second patient treatment with the dopaminergic agonist bromocriptine led to a temporal amelioration of hyperthyroidism. In the third patient, who was the only one with a proven pituitary adenoma, hypersecretion of TSH could be controlled by administration of the somatostatin analogue octreotide. It is emphasized that patients with this disorder should preferably not be treated with thyrostatic drugs, radioactive iodine or thyroid surgery. The success rate of these treatment modalities is lower than normal, they may lead to an increase of goiter size, and they potentially may promote growth or development of a TSH-producing adenoma. Treatment should be aimed at diminishing TSH hypersecretion.

[Treatment on fatigue of patients with postpolio syndrome. A systematic review].

PubMed

Aguila-Maturana, Ana M; Alegre-De Miquel, Cayetano

2010-05-16

Fatigue is the most common symptom and the most disabling in patients with post-polio syndrome. To analyze the effectiveness of various treatments used to improve fatigue syndrome patients post-polio. Systematic review. Is defined a bibliographic search strategy in Medline (from 1961), EMBASE (from 1980), ISI Web of Knowledge and Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), AMED (January 1985), EMI and Physiotherapy Evidence Database (PEDro) until February 2008, the population defined (post-polio syndrome patients) and intervention (any treatment for fatigue in these patients). Outcome were selected as different scales of fatigue and fatigue or vitality dimension scales quality of life. Clinical trials were selected. We retrieved 396 articles, of which 23 were analyzed in detail. Finally, 19 were included in the analysis, a total of 705 patients. Lamotrigine, bromocriptine, aerobics and flexibility exercises, hydrokinesitherapy and technical aids are treatment techniques that reduce more fatigue in these patients.

Effect of Silitidil, a standardized extract of milk thistle, on the serum prolactin levels in female rats.

PubMed

Capasso, Raffaele

2014-07-01

The aim of this study was to assess the effect of Silitidil, a standardized extract of milk thistle, on the serum levels of prolactin in female rats. A 14-day treatment with Silitidil (25-200 mg/kg, per os), a standardized extract of Silybum marianum fruits (milk thistle), increased, in a dose dependent manner, the serum prolactin levels in female rats. Galega (200 mg/kg, per os) given alone neither modified the basal levels of prolactin nor increased further serum prolactin levels when associated with Silitidil. Bromocriptine (1 mg/kg, per os) significantly reduced the high serum prolactin levels induced by Silitidil (200 mg/kg, per os). The results show that the extract of S. marianum fruits significantly increases prolactin levels in female rats; this effect is not potentiated by galega and seems to involve, at least in part, dopamine D2 receptors.

The use of lisuride in the treatment of multiple system atrophy with autonomic failure (Shy-Drager syndrome).

PubMed Central

Lees, A J; Bannister, R

1981-01-01

In a controlled trial lisuride, an ergolene derivative with dopamine receptor agonist properties was given maximum tolerated doses (2.4 mg/day) to seven patients with multiple system atrophy with autonomic failure (Shy-Drager syndrome). Improvement in Parkinsonian features occurred in only one patient and another patient who had been deriving marked benefit from levodopa treatment before the study began failed to respond to large doses of lisuride. Psychiatric side effects (including nightmares, isolated visual hallucinations and toxic confusional states) were the dose-limiting factor in six patients. A modest reduction in orthostatic hypotension occurred in two patients, one of whom had experienced an aggravation of this disturbance on levodopa and bromocriptine. Destruction of post-synaptic dopamine receptors and damage to central noradrenergic systems may offer an explanation for the lack of therapeutic effect of lisuride. PMID:7241162

Mucuna pruriens (L.) DC chemo sensitize human breast cancer cells via downregulation of prolactin-mediated JAK2/STAT5A signaling.

PubMed

Sinha, Sonam; Sharma, Sonal; Vora, Jaykant; Shah, Heta; Srivastava, Anshu; Shrivastava, Neeta

2018-05-10

Mucuna pruriens (L.) DC (MP) is an ancient Indian medicinal plant traditionally used to treat Parkinson's disease. L-Dopa (LD), precursor of dopamine is abundantly found in the seeds of MP. L-dopa is a natural inhibitor of prolactin (PRL) hormone which is required to maintain lactation in women but it's over production (hyperprolactinemia) plays critical role in advancement of breast cancer. We aim to examine the pharmacological effect of LD and MP on this hyperprolactinemia associated breast cancer and related signaling for effective management of the disease. We also investigated chemo-sensitizing effect of MP on hyperprolactinemia-mediated cisplatin resistance. Methanolic seed extract of MP were prepared and analysed using HPLC. Effect of LD and MP on the cellular viability of breast cancer cells (T47D, MCF-7, MDA-MB-468 and MDA-MB-231) were evaluated using MTT assay. Further, effect of LD and MP on colony forming potential, DNA damage, cell cycle distribution and apoptosis was determined using agar/agarose method, comet assay and annexin and PI method followed by FACS analysis. To reveal the molecular mechanism involved in the anti-cancer activity of MP, transcriptional and translational level analysis of the key proteins involved in the PRL-mediated signaling, was performed using RT-PCR and western blot analysis. The effect of MP extract on PRL-mediated signaling was validated using dopaminergic agonist bromocriptine. MP extract and cisplatin was given in different combination with appropriate controls to check their effect on chemo-resistivity of breast cancer cells. Our results demonstrated that MP seed extract has the potential to inhibit cellular proliferation of PRL expressing T47D and MCF-7 breast cancer cells via induction of DNA damage, G1 phase of cell cycle arrest and apoptosis more effectively as compare to LD. Further, MP-mediated anti-cancerous effect was associated with the downregulation of PRL expression, further suppressing the JAK2/STAT5A/Cyclin D1 signaling pathway which has been validated using dopaminergic agonist bromocriptine. Cancer-related hyperprolactinemia confers cisplatin resistance, we observed that MP via PRL inhibition, enhances cisplatin efficacy after their combinatorial treatment in breast cancer cells. Collectively, our study suggests that MP could be recommended as dietary supplement along with the chemotherapeutic agents against breast cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

Cost-Effectiveness Analysis of Microscopic and Endoscopic Transsphenoidal Surgery Versus Medical Therapy in the Management of Microprolactinoma in the United States.

PubMed

Jethwa, Pinakin R; Patel, Tapan D; Hajart, Aaron F; Eloy, Jean Anderson; Couldwell, William T; Liu, James K

2016-03-01

Although prolactinomas are treated effectively with dopamine agonists, some have proposed curative surgical resection for select cases of microprolactinomas to avoid life-long medical therapy. We performed a cost-effectiveness analysis comparing transsphenoidal surgery (either microsurgical or endoscopic) and medical therapy (either bromocriptine or cabergoline) with decision analysis modeling. A 2-armed decision tree was created with TreeAge Pro Suite 2012 to compare upfront transsphenoidal surgery versus medical therapy. The economic perspective was that of the health care third-party payer. On the basis of a literature review, we assigned plausible distributions for costs and utilities to each potential outcome, taking into account medical and surgical costs and complications. Base-case analysis, sensitivity analysis, and Monte Carlo simulations were performed to determine the cost-effectiveness of each strategy at 5-year and 10-year time horizons. In the base-case scenario, microscopic transsphenoidal surgery was the most cost-effective option at 5 years from the time of diagnosis; however, by the 10-year time horizon, endoscopic transsphenoidal surgery became the most cost-effective option. At both time horizons, medical therapy (both bromocriptine and cabergoline) were found to be more costly and less effective than transsphenoidal surgery (i.e., the medical arm was dominated by the surgical arm in this model). Two-way sensitivity analysis demonstrated that endoscopic resection would be the most cost-effective strategy if the cure rate from endoscopic surgery was greater than 90% and the complication rate was less than 1%. Monte Carlo simulation was performed for endoscopic surgery versus microscopic surgery at both time horizons. This analysis produced an incremental cost-effectiveness ratio of $80,235 per quality-adjusted life years at 5 years and $40,737 per quality-adjusted life years at 10 years, implying that with increasing time intervals, endoscopic transsphenoidal surgery is the more cost-effective treatment strategy. On the basis of the results of our model, transsphenoidal surgical resection of microprolactinomas, either microsurgical or endoscopic, appears to be more cost-effective than life-long medical therapy in young patients with life expectancy greater than 10 years. We caution that surgical resection for microprolactinomas be performed only in select cases by experienced pituitary surgeons at high-volume centers with high biochemical cure rates and low complication rates. Copyright © 2016 Elsevier Inc. All rights reserved.

Dopamine Modulates Adaptive Prediction Error Coding in the Human Midbrain and Striatum.

PubMed

Diederen, Kelly M J; Ziauddeen, Hisham; Vestergaard, Martin D; Spencer, Tom; Schultz, Wolfram; Fletcher, Paul C

2017-02-15

Learning to optimally predict rewards requires agents to account for fluctuations in reward value. Recent work suggests that individuals can efficiently learn about variable rewards through adaptation of the learning rate, and coding of prediction errors relative to reward variability. Such adaptive coding has been linked to midbrain dopamine neurons in nonhuman primates, and evidence in support for a similar role of the dopaminergic system in humans is emerging from fMRI data. Here, we sought to investigate the effect of dopaminergic perturbations on adaptive prediction error coding in humans, using a between-subject, placebo-controlled pharmacological fMRI study with a dopaminergic agonist (bromocriptine) and antagonist (sulpiride). Participants performed a previously validated task in which they predicted the magnitude of upcoming rewards drawn from distributions with varying SDs. After each prediction, participants received a reward, yielding trial-by-trial prediction errors. Under placebo, we replicated previous observations of adaptive coding in the midbrain and ventral striatum. Treatment with sulpiride attenuated adaptive coding in both midbrain and ventral striatum, and was associated with a decrease in performance, whereas bromocriptine did not have a significant impact. Although we observed no differential effect of SD on performance between the groups, computational modeling suggested decreased behavioral adaptation in the sulpiride group. These results suggest that normal dopaminergic function is critical for adaptive prediction error coding, a key property of the brain thought to facilitate efficient learning in variable environments. Crucially, these results also offer potential insights for understanding the impact of disrupted dopamine function in mental illness. SIGNIFICANCE STATEMENT To choose optimally, we have to learn what to expect. Humans dampen learning when there is a great deal of variability in reward outcome, and two brain regions that are modulated by the brain chemical dopamine are sensitive to reward variability. Here, we aimed to directly relate dopamine to learning about variable rewards, and the neural encoding of associated teaching signals. We perturbed dopamine in healthy individuals using dopaminergic medication and asked them to predict variable rewards while we made brain scans. Dopamine perturbations impaired learning and the neural encoding of reward variability, thus establishing a direct link between dopamine and adaptation to reward variability. These results aid our understanding of clinical conditions associated with dopaminergic dysfunction, such as psychosis. Copyright © 2017 Diederen et al.

Catatonia, Neuroleptic Malignant Syndrome, and Cotard Syndrome in a 22-Year-Old Woman: A Case Report

PubMed Central

Weiss, C.; Santander, J.; Torres, R.

2013-01-01

The following case study describes a 22-year-old woman with depression and symptoms of psychosis who developed neuroleptic malignant syndrome after using Risperidone, thus requiring life support equipment and Bromocriptine, later recovering after seven days. From a psychiatric and neurological point of view, however, the persistence of catatonic syndrome and Cotard syndrome delusions was observed, based on assertions such as “I do not have a heart,” “my heart is not beating,” “I can not breathe,” “I am breaking apart,” “I have no head” (ideas of negation) and statements about the patient being responsible for the “death of the whole world” (ideas of enormity). Brain NMR revealed leukoencephalopathy, interpreted as scar lesions caused by perinatal neurological damage, after discarding other pathologies. The patient responded well to electroconvulsive therapy after 11 sessions. Organic vulnerability to these syndromes, as well as their coexistence and clinical differentiation is discussed in the light of the data observed. PMID:24093068

Catatonia, neuroleptic malignant syndrome, and cotard syndrome in a 22-year-old woman: a case report.

PubMed

Weiss, C; Santander, J; Torres, R

2013-01-01

The following case study describes a 22-year-old woman with depression and symptoms of psychosis who developed neuroleptic malignant syndrome after using Risperidone, thus requiring life support equipment and Bromocriptine, later recovering after seven days. From a psychiatric and neurological point of view, however, the persistence of catatonic syndrome and Cotard syndrome delusions was observed, based on assertions such as "I do not have a heart," "my heart is not beating," "I can not breathe," "I am breaking apart," "I have no head" (ideas of negation) and statements about the patient being responsible for the "death of the whole world" (ideas of enormity). Brain NMR revealed leukoencephalopathy, interpreted as scar lesions caused by perinatal neurological damage, after discarding other pathologies. The patient responded well to electroconvulsive therapy after 11 sessions. Organic vulnerability to these syndromes, as well as their coexistence and clinical differentiation is discussed in the light of the data observed.

Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review.

PubMed

Gillman, P Ken

2010-02-01

The US Food and Drug Administration (FDA) have suggested that fatal serotonin syndrome (SS) is possible with selective serotonin reuptake inhibitors (SSRIs) and triptans: this warning affects millions of patients as these drugs are frequently given simultaneously. SS is a complex topic about which there is much misinformation. The misconception that 5-HT1A receptors can cause serious SS is still widely perpetuated, despite quality evidence that it is activation of the 5-HT2A receptor that is required for serious SS. This review considers SS involving serotonin agonists: ergotamine, lysergic acid diethylamide, bromocriptine, and buspirone, as well as triptans, and reviews the experimental foundation underpinning the latest understanding of SS. It is concluded that there is neither significant clinical evidence, nor theoretical reason, to entertain speculation about serious SS from triptans and SSRIs. The misunderstandings about SS exhibited by the FDA, and shared by the UK Medicines and Healthcare products Regulatory Agency (in relation to methylene blue), are an important issue with wide ramifications.

Jasmine flower extract lowers prolactin.

PubMed

Finny, Philip; Stephen, Charles; Jacob, Rajesh; Tharyan, Prathap; Seshadri, Mandalam S

2015-04-01

Antipsychotic drugs frequently cause amenorrhoea and galactorrhoea. Jasmine flowers used topically were as effective as oral Bromocriptine in suppressing puerperal lactation. This study aims to evaluate the efficacy and safety of intranasal jasmine flower extract (JFE) to reduce prolactin levels of patients on stable doses of antipsychotic drugs. This is a randomized, double blind, crossover clinical trial. An aqueous-ethanol extract of jasmine flowers was prepared and used as nasal drops. A decrease in serum prolactin of ≥25 ng/mL was considered a significant response. Ten out of 35 women had a significant drop in the serum prolactin while on the JFE. The non-responders to JFE were on higher doses of antipsychotic drugs. The main side effect was a transient and mild burning sensation in the nose. A cost analysis favoured JFE over dopamine agonists. JFE contains a prolactin-lowering substance which needs further characterisation. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Regulation of hormone release by cultured cells from a thyrotropin-growth hormone-secreting pituitary tumor. Direct inhibiting effects of 3,5,3'-triiodothyronine and dexamethasone on thyrotropin secretion.

PubMed

Lamberts, S W; Oosterom, R; Verleun, T; Krenning, E P; Assies, H

1984-08-01

The regulation of TSH and GH secretion was investigated in cultured tumor cells prepared from a mixed TSH/GH secreting pituitary tumor. The tumor tissue had been removed transsphenoidally from a patient with hyperthyroidism and inappropriately high serum TSH levels and acromegaly. TSH and GH secretion by cultured cells were stimulated in a parallel way by TRH (300 nM) and LHRH (50 nM), but were unaffected by bromocriptine (10 nM). Exposure of the tumor cells to dexamethasone (0.1 microM) or T3 (50 nM) had differential effects on hormone secretion. GH secretion was greatly stimulated by dexamethasone, but unaffected by T3. TSH secretion was inhibited both by T3 and by dexamethasone. So, T3 and glucocorticoids inhibit TSH release by the human pituitary tumor cells studied at least partly by means of a direct effect.

Absence of detectable immunoreactive alpha melanocyte stimulating hormone in plasma in various types of Cushing's disease.

PubMed

Croughs, R J; Thijssen, J H; Mol, J A

1991-03-01

We have measured alpha-MSH in plasma of normal subjects and subjects with various diseases of the pituitary-adrenocortical system using a radioimmunoassay with a sensitivity of 1.2 pmol/l. No alpha-MSH could be detected in plasma of normal subjects (n = 6), in plasma of patients with Addison's disease (n = 3), Nelson's syndrome (n = 2), bromocriptine responsive (n = 2) and unresponsive (n = 5) Cushing's disease and in plasma of psychiatric patients on chronic treatment with the dopamine antagonist haloperidol (n = 5). Plasma alpha-MSH remained undetectable in 2 patients with Cushing's disease after iv injection of 60 micrograms/kg haloperidol. In contrast, alpha-MSH was detectable in plasma of normal dogs (n = 2) and dogs with pituitary dependent hyperadrenocorticism (n = 2), whereas the iv injection of halo peridol was associated with a rise of plasma alpha-MSH. Thus we are unable to detect circulating alpha-MSH in man despite the use of a sensitive radioimmunoassay.

[Case of neuroleptic malignant syndrome following open heart surgery for thoracic aortic aneurysm with parkinson's disease].

PubMed

Shinoda, Maiko; Sakamoto, Mik; Shindo, Yuki; Ando, Yumi; Tateda, Takeshi

2013-12-01

An 80-year-old woman with Parkinson's disease was scheduled for open heart surgery to repair thoracic aortic aneurysm. Parkinson's symptoms were normally treated using oral levodopa (200 mg), selegiline-hydrochloride (5 mg), bromocriptine-mesilate (2 mg), and amantadine-hydrochloride (200 mg) daily. On the day before surgery, levodopa 50mg was infused intravenously. Another 25 mg of levodopa was infused immediately after surgery. Twenty hours later, the patient developed tremors, heyperventilation, but no obvious muscle rigidity. Two days after surgery, the patient exhibited high fever, hydropoiesis, elevated creatine kinase, and a rise in blood leukocytes. She was diagnosed with neuroleptic malignant syndrome. She was intubated, and received dantrolene sodium. Symptoms of neuroleptic malignant syndrome disappeared on the fourth postoperative day. The stress of open heart surgery, specifically extracorporeal circulation and concomitant dilution of levodopa, triggered neuroleptic malignant syndrome in this patient. Parkinson's patients require higher doses of levodopa prior to surgery to compensate and prevent neuroleptic malignant syndrome after surgery.

[Sexual delinquency and Parkinson's disease].

PubMed

Berger, Ch; Mehrhoff, F W; Beier, K M; Meinck, H-M

2003-04-01

The risk of aberrant sexual behaviour such as hypersexuality, exhibitionism, or pederasty may be underestimated in Parkinson's disease and its therapy with high-dosage L-dopa or dopamine agonists. We describe two legal cases which are representative of the forensic assessment of these side effects. The first case brought to court was a 45-year-old man suffering for 20 years from Parkinson's disease who developed hypersexuality and exhibitionism under high-dose therapy with ropinirol. The second patient, a 57-year-old man with an 11-year history of Parkinson's disease, developed increased libido and pederasty under therapy with L-dopa and bromocriptine. We discuss the present literature concerning hypersexuality and sexually deviant behaviour in Parkinson's disease and dopaminergic therapy in the German legal context. Doctors treating Parkinson patients should be aware of increased sexual impulses or reduced behavioural control and ask specifically about them during anamnesis, and counteractive therapeutic strategies should be considered to prevent the occurrence of illegal sexually aberrant behavioural disorders.

Gestational Gigantomastia Complicating Pregnancy: A Case Report and Review of the Literature

PubMed Central

Rezai, Shadi; Nakagawa, Jenna T.; Tedesco, John; Chadee, Annika; Gottimukkala, Sri; Mercado, Ray; Henderson, Cassandra E.

2015-01-01

Background. Gestational gigantomastia is a rare disorder without clear etiology or well-established risk factors. Several pathogenic mechanisms contributing to the disease process have been proposed, all of which can lead to a similar phenotype of breast hypertrophy. Case. A 28-year-old Guinean woman presented at 37 weeks of gestation with bilateral gigantomastia, mastalgia, peau d'orange, and back pain. Prolactin levels were 103.3 μg/L (with a normal reference value for prolactin in pregnancy being 36–372 μg/L). The patient was treated with bromocriptine (2.5 mg twice daily), scheduled for a repeat cesarean, and referred to surgery for bilateral mammoplasty. Conclusion. Gestational gigantomastia is a rare disorder, characterized by enlargement and hypertrophy of breast tissue. Our patient presented with no endocrine or hematological abnormalities, adding to a review of the literature for differential diagnoses, workup, and management of cases of gestational gigantomastia with normal hormone levels. PMID:26713166

151. Bromocriptine Challenge Affects Working Memory Processing in Humans Depending on DRD2-Related Genes

PubMed Central

Pergola, Giulio; Selvaggi, Pierluigi; Gelao, Barbara; Di Carlo, Pasquale; Nettis, Maria Antonietta; Amico, Graziella; Felici, Valentina; Fazio, Leonardo; Rampino, Antonio; Sambataro, Fabio; Blasi, Giuseppe; Bertolino, Alessandro

2017-01-01

Abstract Background: Dopamine D2 receptors (D2R) contribute to the inverted-U shaped relationship between dopamine dorsolateral prefrontal cortex (DLPFC) and working memory (WM). Genetic variation in DRD2 coding for D2Rs modulates D2 signaling, but other genes in its pathway may be involved. In a previous work, using gene co-expression networks we identified 84 partner genes coregulated with DRD2 and eight single nucleotide polymorphisms (SNPs) predicting coexpression of the whole gene set in the human DLPFC [1]. These SNPs combined into a polygenic coexpression index (PCI) predicted WM performance and DLPFC activity in two independent samples of living healthy humans [1]. Here, we asked whether response to D2R targeting drugs is associated with this PCI. Thus, we investigated the interaction between WM behavioral/brain response to the D2R agonist Bromocriptine (BRO) and the PCI. [1] Pergola G, Di Carlo P, et al. (In press). Translational Psychiatry. Methods: Fifty healthy volunteers entered a double-blind, crossover, randomized, placebo-controlled fMRI study with BRO 1.25 mg and performed the N-Back WM task during the fMRI scanning session. We computed the PCI for all participants and investigated its association with WM-related behavior and brain activity using general linear models. Results: A PCI by drug interaction was significant on both DLPFC signal (right BA46, 242 voxels, F(1, 48) = 24; right BA9, 177 voxels, F(1, 48) = 19; P < .05 cluster-level FWE corrected) and behavioral scores, F(1, 46) = 4.6, P = .045, using a U-shaped quadratic model. The U-shaped relationship between the PCI and WM processing found on placebo was reversed on BRO. Furthermore, the increase in behavioral performance on BRO correlated with a decrease in BA46 activity, t(48) = −2.0, P = .049). Conclusion: The combined effect of multiple alleles on DRD2 coexpression covaried with drug response such that different allelic patterns were associated with similar responses, as in the inverted U-shaped model of WM. Thus, multiple genes and multiple allelic patterns are implicated in the inverted U-shaped dopamine/WM relationship. This relationship is reversed when individuals are administered BRO, suggesting that brain and behavioral response to this pharmacological challenge depends on a pleiotropic individual genetic background. Hence, pharmacogenomics in schizophrenia should take into account allelic patterns associated with molecular phenomena such as gene expression to predict drug response.

Effectiveness of Matricaria chamomilla (chamomile) extract on pain control of cyclic mastalgia: a double-blind randomised controlled trial.

PubMed

Saghafi, N; Rhkhshandeh, H; Pourmoghadam, N; Pourali, L; Ghazanfarpour, M; Behrooznia, A; Vafisani, F

2018-01-01

Breast pain (mastalgia) often precedes menstrual period, which is of mild to moderate severity. This study was performed to determine the effectiveness of chamomile on pain control of cyclic mastalgia. This double-blind randomised controlled clinical trial was conducted on 60 patients with mastalgia referred to the breast clinic of an academic hospital, Mashhad University of Medical Sciences. The patients were randomly allocated into two groups: chamomile (n = 30) and placebo (n = 30). Primary outcomes were: (1) assessment of the visual analogue scale (VAS) and (2) assessment of the breast pain chart (BPC) 8 weeks after initial intervention. All the participants were asked to take drops three times a day each time having five drops for two consecutive months. Significant decline was observed in both the groups (chamomile and placebo) after two months (p < .0001 and p = .048, respectively) compared to baseline and between two groups (p = .007). Chamomile was a well-tolerated, secure and effective drug for treating women with mild to moderate mastalgia. Impact statement What is already known on this subject: Breast pain (mastalgia) is a common chief complaint reported by many women. The 'cyclic' type, which usually occurs monthly prior to the onset of menstrual period, is of moderate severity. In 30% of the cases, mastalgia is severe and disturbs normal life, leading to sexual, physical, and social dysfunction as well as depression and anxiety. The cause of cyclical mastalgia is not known, but given the fact that it begins in the luteal phase, it can be caused by hormonal stimulation. A variety of therapies have been recommended. Such therapies include prescription of vitamin B2, B6, E and C, non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, thyroxin, progesterone, Tamoxifen, Danazol, Bromocriptine and plant extracts like vitexagnus castus, evening primrose oil (EPO). However, given the side effects of hormonal treatment, many women have developed a propensity towards the use of herbal medicine. What do the results of this study add: Chamomile presents a safe, well-tolerated and effective treatment for women with moderate mastalgia. What are the implications of these finding for clinical practice and/or further research: Considering that Danazol, Bromocriptine and Tamoxifen are standard treatments for mastalgia, it would be helpful to carry out a trial study to compare the effect of chamomile extract versus standard treatments. The physicians can prescribe chamomile as a safe alternative treatment for mastalgia.

Effect of bromocriptine-QR therapy on glycemic control in subjects with type 2 diabetes mellitus whose dysglycemia is inadequately controlled on insulin.

PubMed

Chamarthi, Bindu; Cincotta, Anthony H

2017-05-01

The concurrent use of an insulin sensitizer in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control on basal-bolus insulin may help improve glycemic control while limiting further insulin requirement. Bromocriptine-QR (B-QR), a quick release, sympatholytic, dopamine D2 receptor agonist therapy for T2DM, is a postprandial insulin sensitizer. This study evaluated the effect of B-QR on dysglycemia in T2DM subjects with suboptimal glycemic control on basal-bolus insulin plus metformin. The effect of once-daily morning administration of B-QR on dysglycemia was evaluated in 60 T2DM subjects derived from the Cycloset Safety Trial, with HbA1c >7% on basal-bolus insulin plus metformin at baseline, randomized to B-QR (N = 44) versus placebo (N = 16) and completed 12 weeks of study drug treatment. The analyses also included a subset of subjects on high-dose insulin (total daily insulin dose (TDID) ≥70 units; N = 36: 27 B-QR; 9 placebo). Subjects were well matched at baseline. After 12 weeks of B-QR treatment, mean % HbA1c decreased by -0.73% relative to baseline (p < 0.001) and by -1.13 relative to placebo (p < 0.001). In the high-dose insulin subset, B-QR therapy resulted in % HbA1c reductions of -0.95 and -1.49 relative to baseline (p < 0.001) and placebo (p = 0.001) respectively. Secondary analyses of treatment effect at 24 and 52 weeks demonstrated similar influences of B-QR on HbA1c. The fasting plasma glucose (FPG) and TDID changes within each treatment group were not significant. More subjects achieved HbA1c ≤7 at 12 weeks with B-QR relative to placebo (36.4% B-QR vs 0% placebo, Fisher's exact 2-sided p = 0.003 in the entire cohort and 37% vs 0%, 2-sided p = 0.039 in the high-dose insulin subset). B-QR therapy improves glycemic control in T2DM subjects whose glycemia is poorly controlled on metformin plus basal-bolus insulin, including individuals on high-dose basal-bolus insulin. This glycemic impact occurred without significant change in FPG, suggesting a postprandial glucose lowering mechanism of action. Cycloset Safety Trial registration: ClinicalTrials.gov Identifier: NCT00377676.

Prolactin release, oestrogens and proliferation of prolactin-secreting cells in the anterior pituitary gland of adult male rats.

PubMed

Pérez, R L; Machiavelli, G A; Romano, M I; Burdman, J A

1986-03-01

Relationships among the release of prolactin, the effect of oestrogens and the proliferation of prolactin-secreting cells were studied under several experimental conditions. Administration of sulpiride or oestradiol released prolactin and stimulated cell proliferation in the anterior pituitary gland of adult male rats. Clomiphene completely abolished the rise in cell proliferation, but did not interfere with the sulpiride-induced release of prolactin. Treatment with oestradiol plus sulpiride significantly increased serum prolactin concentrations and the mitotic index compared with the sum of the stimulation produced by both drugs separately. Bromocriptine abolished the stimulatory effect of oestradiol on the serum prolactin concentration and on cell proliferation. In oestradiol- and/or sulpiride-treated rats, 80% of the cells in mitoses were lactotrophs. The remaining 20% did not stain with antisera against any of the pituitary hormones. The number of prolactin-secreting cells in the anterior pituitary gland significantly increased after the administration of oestradiol or sulpiride. The results demonstrate that treatment with sulpiride and/or oestradiol increases the proliferation and the number of lactotrophs in the anterior pituitary gland of the rat.

A well-refined in vitro model derived from human embryonic stem cell for screening phytochemicals with midbrain dopaminergic differentiation-boosting potential for improving Parkinson's disease.

PubMed

Hsieh, Wen-Ting; Chiang, Been-Huang

2014-07-09

Stimulation of endogenous neurogenesis is a potential approach to compensate for loss of dopaminergic neurons of substantia nigra compacta nigra (SNpc) in patients with Parkinson's disease (PD). This objective was to establish an in vitro model by differentiating pluripotent human embryonic stem cells (hESCs) into midbrain dopaminergic (mDA) neurons for screening phytochemicals with mDA neurogenesis-boosting potentials. Consequently, a five-stage differentiation process was developed. The derived cells expressed many mDA markers including tyrosine hydroxylase (TH), β-III tubulin, and dopamine transporter (DAT). The voltage-gated ion channels and dopamine release were also examined for verifying neuron function, and the dopamine receptor agonists bromocriptine and 7-hydroxy-2-(dipropylamino)tetralin (7-OH-DPAT) were used to validate our model. Then, several potential phytochemicals including green tea catechins and ginsenosides were tested using the model. Finally, ginsenoside Rb1 was identified as the most potent phytochemical which is capable of upregulating neurotrophin expression and inducing mDA differentiation.

McCune-Albright syndrome: growth hormone and prolactin hypersecretion.

PubMed

Christoforidis, Athanasios; Maniadaki, Ilianna; Stanhope, Richard

2006-05-01

McCune-Albright syndrome (MAS) has a special interest for endocrinologists as its pathogenesis results in hypersecretion of hormones in peripheral endocrine tissues. This can be expressed as precocious puberty, mainly in girls, primary hyperthyroidism, growth hormone (GH) and/or prolactin excess, hyperparathyroidism and hypercortisolism. The incidence of GH excess among patients with MAS has been assessed as up to 21%. The pathogenesis of GH hypersecretion in MAS is not completely understood, whereas it seems to be different from the aetiology of acromegaly/gigantism in non-MAS patients. The clinical expression of GH excess can be masked because of precocious puberty or craniofacial fibrous dysplasia, indicating the necessity for screening. Medical treatment is usually the only option in MAS patients with GH excess, as transsphenoidal surgery is usually restricted due to massive thickening of the skull base, whereas radiotherapy is contraindicated due to probable higher predisposition to sarcomatous transformation. The use of bromocriptine, cabergoline and octreotide, or the combination of these, has shown variable results, whereas pegvisomant, a GH receptor antagonist, is a new promising option, although not yet used in patients with MAS.

[Early recurrent miscarriage: Evaluation and management].

PubMed

Gallot, V; Nedellec, S; Capmas, P; Legendre, G; Lejeune-Saada, V; Subtil, D; Nizard, J; Levêque, J; Deffieux, X; Hervé, B; Vialard, F

2014-12-01

To establish recommendations for early recurrent miscarriages (≥3 miscarriages before 14weeks of amenorrhea). Literature review, establishing levels of evidence and recommendations for grades of clinical practice. Women evaluation includes the search for a diabetes (grade A), an antiphospholipid syndrome (APS) (grade A), a thyroid dysfunction (grade A), a hyperprolactinemia (grade B), a vitamin deficiency and a hyperhomocysteinemia (grade C), a uterine abnormality (grade C), an altered ovarian reserve (grade C), and a couple chromosome analysis (grade A). For unexplained early recurrent miscarriages, treatment includes folic acid and progesterone supplementation, and a reinsurance policy in the first quarter (grade C). It is recommended to prescribe the combination of aspirin and low-molecular-weight heparin when APS (grade A), glycemic control in diabetes (grade A), L-Thyroxine in case of hypothyroidism (grade A) or the presence of thyroid antibodies (grade B), bromocriptine if hyperprolactinemia (grade B), a substitution for vitamin deficiency or hyperhomocysteinemia (grade C), sectionning a uterine septum (grade C) and treating an uterine acquired abnormality (grade C). These recommendations should improve the management of couples faced with early recurrent miscarriages. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Low levels of PRB3 mRNA are associated with dopamine-agonist resistance and tumor recurrence in prolactinomas.

PubMed

Wang, Fei; Gao, Hua; Li, Chuzhong; Bai, Jiwei; Lu, Runchun; Cao, Lei; Wu, Yongtu; Hong, Lichuan; Wu, Yonggang; Lan, Xiaolei; Zhang, Yazhuo

2014-01-01

Prolactinomas, or prolactin-secreting adenomas, constitute the most common type of hyperfunctioning pituitary adenoma. Dopamine agonists are used as first-line medication for prolactinomas, but the tumors are resistant to the therapy in 5-18 % of patients. To explore potential mechanisms of resistance to bromocriptine (a dopamine agonist), we analyzed six responsive prolactinomas and six resistant prolactinomas by whole-exome sequencing. We identified ten genes with sequence variants that were differentially found in the two groups of tumors. The expression of these genes was then quantified by real-time reverse-transcription PCR (RT-qPCR) in the 12 prolactinomas and in six normal pituitary glands. The mRNA levels of one of the genes, PRB3, were about fourfold lower in resistant prolactinomas than in the responsive tumors (p = 0.02). Furthermore, low PRB3 expression was also associated with tumor recurrence. Our results suggest that low levels of PRB3 mRNA may have a role in dopamine-agonist resistance and tumor recurrence of prolactinomas.

Peripartum Cardiomyopathy Treatment with Dopamine Agonist and Subsequent Pregnancy with a Satisfactory Outcome.

PubMed

Melo, Maria Adélia Medeiros E; Carvalho, Jordão Sousa; Feitosa, Francisco Edson de Lucena; Araujo Júnior, Edward; Peixoto, Alberto Borges; Costa Carvalho, Francisco Herlânio; Carvalho, Regina Coeli Marques

2016-06-01

Pathophysiological mechanisms of peripartum cardiomyopathy are not yet completely defined, although there is a strong association with various factors that are already known, including pre-eclampsia. Peripartum cardiomyopathy treatment follows the same recommendations as heart failure with systolic dysfunction. Clinical and experimental studies suggest that products of prolactin degradation can induce this cardiomyopathy. The pharmacological suppression of prolactin production by D2 dopamine receptor agonists bromocriptine and cabergoline has demonstrated satisfactory results in the therapeutic response to the treatment. Here we present a case of an adolescent patient in her first gestation with peripartum cardiomyopathy that evolved to the normalized left ventricular function after cabergoline administration, which was used as an adjuvant in cardiac dysfunction treatment. Subsequently, despite a short interval between pregnancies, the patient exhibited satisfactory progress throughout the entire gestation or puerperium in a new pregnancy without any cardiac alterations. Dopamine agonists that are orally used and are affordable in most tertiary centers, particularly in developing countries, should be considered when treating peripartum cardiomyopathy cases. Thieme Publicações Ltda Rio de Janeiro, Brazil.

Dopaminergic contributions to working memory-related brain activation in postmenopausal women.

PubMed

Dumas, Julie A; Filippi, Christopher G; Newhouse, Paul A; Naylor, Magdalena R

2017-02-01

The current study examined the effects of pharmacologic dopaminergic manipulations on working memory-related brain activation in postmenopausal women to further understand the neurochemistry underlying cognition after menopause. Eighteen healthy postmenopausal women, mean age 55.21 years, completed three study days with dopaminergic drug challenges during which they performed a functional magnetic resonance imaging visual verbal N-back test of working memory. Acute stimulation with 1.25 mg oral D2 agonist bromocriptine, acute blockade with 1.5 mg oral haloperidol, and matching placebo were administered randomly and blindly on three study days. We found that dopaminergic stimulation increased activation primarily in the posterior regions of the working memory network compared with dopaminergic blockade using a whole brain cluster-level corrected analysis. The dopaminergic medications did not affect working memory performance. Patterns of increased blood-oxygen-level dependent signal activation after dopaminergic stimulation were found in this study in posterior brain regions with no effect on working memory performance. Further studies should examine specific dopaminergic contributions to brain functioning in healthy postmenopausal women to determine the effects of the increased brain activation on cognition and behavior.

McCune Albright syndrome in association with excessive GH secretion: case report.

PubMed

Özsu, Elif; Mutlu, Gül Yeşiltepe; Çizmecioğlu, Filiz Mine; Hatun, Şükrü

2015-06-01

McCune-Albright Syndrome is a rare syndrome characterized with excessive function of peripheral endocrine organs and activating mutations of the stimulatory G protein alpha subunit are involved in the pathogenesis. The three main findings of the disease include hyperpigmented café au lait spots, fibrous dysplasia and increased endocrine functions and excessive secretion of growth hormone is observed in 21% of the patients. Clinical signs may be missed in these patients because of precocious puberty and craniofacial fibrous dysplasia. Since radiotherapy causes to sarcomatous changes and transsphenoidal surgery may cause to severe thickening in the cranial bones, they are not appropriate treatment options and medical treatment is recommended. Bromocriptine, cabergoline and octreotide or different combinations of these drugs are used in treatment and pegvisomant has also been used in recent years. Here, we present a male patient aged 12 years and 7 months to show gigantism as a rare clinical reflection of McCune-Albright Syndrome with an excessive height (197 cm), café au lait spots, growht hormone levels which could not be supressed with oral glucose tolerance test and increased prolactin levels.

Dopamine, T cells and multiple sclerosis (MS).

PubMed

Levite, Mia; Marino, Franca; Cosentino, Marco

2017-05-01

Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others. Interestingly, dopamine activates resting effector T cells (Teffs), but suppresses regulatory T cells (Tregs), and both effects lead eventually to Teff activation. Dopamine-induced effects on T cells are dynamic, context-sensitive and determined by the: T cell activation state, T cell type, DR type, and dopamine concentration. Dopamine itself, and also few dopaminergic molecules/ drugs that are in clinical use for cardiac, neurological and other non-immune indications, have direct effects on human T cells (summarized in this review). These dopaminergic drugs include: dopamine = intropin, L-DOPA, bromocriptine, pramipexole, pergolide, haloperidol, pimozide, and amantadine. Other dopaminergic drugs were not yet tested for their direct effects on T cells. Extensive evidence in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) show dopaminergic dysregulations in T cells in these diseases: D1-like DRs are decreased in Teffs of MS patients, and dopamine does not affect these cells. In contrast, D1-like DRs are increased in Tregs of MS patients, possibly causing functional Treg impairment in MS. Treatment of MS patients with interferon β (IFN-β) increases D1-like DRs and decreases D2-like DRs in Teffs, decreases D1-like DRs in Tregs, and most important: restores responsiveness of patient's Teffs to dopamine. DR agonists and antagonists confer some benefits in EAE-afflicted animals. In a single clinical trial, MS patients did not benefit from bromocriptine, which is a D2-like DR agonist. Nevertheless, multiple evidence showing dopaminergic abnormalities in T cells in MS encourages testing other DR analogues/drugs in MS, possibly as "add-on" to IFN-β or other MS-immunomodulating therapies. Together, abnormalities in DRs in T cells can contribute to MS, and DRs in T cells can be therapeutic targets in MS. Finally and in a more general scope: the direct effects of all dopaminergic drugs on human T cells should be studied in further depth, and also taken into consideration whenever treating patients with any disease, to avoid detrimental side effects on the immune system of the patients.

Pituitary tumours in adolescence: clinical behaviour and neuroimaging features of seven cases.

PubMed

Nishio, S; Morioka, T; Suzuki, S; Takeshita, I; Fukui, M; Iwaki, T

2001-05-01

The clinicopathologic features of seven paediatric patients with pituitary adenomas (2 male, 5 female; mean age 14.3 years) were reviewed. There were three non-functioning adenomas, three prolactinomas, and one growth hormone producing adenoma. Five patients presented with visual field deficits, and six patients had endocrine symptoms, which included menstrual irregularities in all female patients, pubertal delay in two females, and growth delay and gigantism in one case each. On neuroimaging studies, five adenomas showed parasellar extension, while the remaining two prolactinomas were intrasellar microadenomas. While two patients with prolactinomas received good results with bromocriptine treatment alone, the remaining five patients underwent either craniotomy or transsphenoidal surgery. Postoperatively, visual disturbances improved markedly in all patients. Two patients also received replacement hormonal therapy. While six patients have been stable for 3.6 years on average, one non-functioning tumour recurred 2 years after the initial transcranial subtotal resection of the tumour. Although there are still many unknowns concerning the biology and optimal treatments for paediatric pituitary adenomas, many of them are assumed to be relatively rapidly growing tumours, while others merely have an earlier tumour genesis than in adults. Copyright 2001 Harcourt Publishers Ltd.

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion.

PubMed

Aslanoglou, Despoina; George, Emily W; Freyberg, Zachary

2018-05-10

The detection of insulin secretion is critical for elucidating mechanisms of regulated secretion as well as in studies of metabolism. Though numerous insulin assays have existed for decades, the recent advent of homogeneous time-resolved Förster Resonance Energy Transfer (HTRF) technology has significantly simplified these measurements. This is a rapid, cost-effective, reproducible, and robust optical assay reliant upon antibodies conjugated to bright fluorophores with long lasting emission which facilitates time-resolved Förster Resonance Energy Transfer. Moreover, HTRF insulin detection is amenable for the development of high-throughput screening assays. Here we use HTRF to detect insulin secretion in INS-1E cells, a rat insulinoma-derived cell line. This allows us to estimate basal levels of insulin and their changes in response to glucose stimulation. In addition, we use this insulin detection system to confirm the role of dopamine as a negative regulator of glucose-stimulated insulin secretion (GSIS). In a similar manner, other dopamine D2-like receptor agonists, quinpirole, and bromocriptine, reduce GSIS in a concentration-dependent manner. Our results highlight the utility of the HTRF insulin assay format in determining the role of numerous drugs in GSIS and their pharmacological profiles.

Dopaminergic modulation of semantic priming in healthy volunteers.

PubMed

Roesch-Ely, Daniela; Weiland, Stephan; Scheffel, Hans; Schwaninger, Markus; Hundemer, Hans-Peter; Kolter, Thomas; Weisbrod, Matthias

2006-09-15

Semantic priming is a function related to prefrontal cortical (PFC) networks and is lateralized. There is evidence that semantic priming underlies dopaminergic modulation. It is known that the D1-receptor is more abundant in prefrontal networks; however, until now there have been no studies investigating the selective modulation of semantic priming with dopamine agonists. Furthermore, D1 receptor dysfunction has been described in schizophrenia, and patients with formal thought disorder seem to have disturbed focusing of associations and increased indirect priming. With a subtraction design, we compared the influence of pergolide (D1/D2 agonist) with bromocriptine (D2 agonist) and placebo, in a randomized, double-blind, crossover design in 40 healthy male volunteers. Subjects performed a lateralized lexical decision task including direct and indirect related prime-target pairs (stimulus onset asynchrony = 750 msec). Only on pergolide a decrease of the indirect priming in the left hemisphere presentations was found. These findings point to a potential selective modulation of agonists with a D1 component on the focusing of semantic associations. The clinical relevance of this study is that it might help the development of therapeutic strategies for treating cognitive deficits in schizophrenia and Parkinson's disease, which are highly relevant to the functional outcome.

Catatonia in Neurologic and Psychiatric Patients at a Tertiary Neurological Center.

PubMed

Espinola-Nadurille, Mariana; Ramirez-Bermudez, Jesus; Fricchione, Gregory L; Ojeda-Lopez, M Carmen; Perez-González, Andres F; Aguilar-Venegas, Luis C

2016-01-01

This study describes the prevalence, phenomenology, treatment, and outcome of neurological patients and psychiatric patients with catatonia at a tertiary neurological center. Clinical variables included nosological diagnoses and complications. Admission length and days with catatonia were used as outcome measures. Of 2,044 patients who were evaluated prospectively, 68 (3.32%) had catatonia, 42 (61.7%) were neurological patients, 19 (27.9%) were psychiatric patients, and 7 (10.2%) had drug-related diagnoses. Of all patients, the ratio of neurological to psychiatric patients was 3:1. Encephalitis was the most common diagnosis (N=26 [38.2%]), followed by schizophrenia (N=12 [17.6%]). Psychiatric patients exhibited a stuporous type of catatonia (15 [83.3%] versus 14 [33.3%], p>0.001), whereas neurological patients exhibited a mixed form of catatonia (25 [59.5%] versus 1 [5.6], p<0.001). Neurological patients had more complications, longer hospitalizations, and more days with catatonia. A total of 56 patients (82.3%) received lorazepam, and 14 patients (20.5%) underwent ECT. Second- and third-line treatments included amantadine, bromocriptine, and levodopa. Catatonia is a prevalent syndrome that can remit with proper and opportune treatment.

Ovulation disorders: part I anovulation associated with estrogen deficiency.

PubMed

Check, J H

2007-01-01

To describe the diagnosis and treatment of anovulatory disorders associated with estrogen deficiency. Anovulation with estrogen deficiency was divided into two types: association with low vs. high serum gonadotropin levels. Treatments included bromocriptine or cabergoline for hyperprolactinemia and gonadotropins for normal prolactin levels. When gonadotropins were low, lowering the elevated serum FSH to restore down-regulated FSH receptors in the few remaining follicles with either ethinyl estradiol or GnRH agonists or antagonists was used. High serum FSH was followed by either close observation for spontaneous follicular maturation or low dose gonadotropin stimulation. Progesterone supplementation, especially by vaginal use, was given in the luteal phase. Though success in ovulation induction and pregnancies was greater in women with low FSH than high FSH, pregnancies following ovulation induction were nevertheless achieved even in women in apparent menopause. The use of ethinyl estradiol as opposed to other estrogen drugs has the advantage of not being able to be measured by most serum assays for estradiol allowing the physician to detect endogenous follicular development and thus determining when follicular maturation has been achieved. Even in the presence of marked diminished ovarian egg reserve, eggs from chronically younger women are superior in quality to women aged > or = 45.

Dopaminergic contributions to working memory-related brain activation in postmenopausal women

PubMed Central

Dumas, Julie A.; Filippi, Christopher G.; Newhouse, Paul A.; Naylor, Magdalena R.

2016-01-01

Objective The current study examined the effects of pharmacologic dopaminergic manipulations on working memory-related brain activation in postmenopausal women to further understand the neurochemistry underlying cognition after menopause. Method Eighteen healthy postmenopausal women, mean age 55.21 years, completed three study days with dopaminergic drug challenges during which they performed an fMRI visual verbal N-back test of working memory. Acute stimulation with 1.25 mg oral D2 agonist bromocriptine, acute blockade with 1.5 mg oral haloperidol, and matching placebo were administered randomly and blindly on three study days. Results We found that dopaminergic stimulation increased activation primarily in the posterior regions of the working memory network compared to dopaminergic blockade using a whole brain cluster-level corrected analysis. The dopaminergic medications did not affect working memory performance. Conclusions Patterns of increased BOLD signal activation after dopaminergic stimulation were found in this study in posterior brain regions with no effect on working memory performance. Further studies should examine specific dopaminergic contributions to brain functioning in healthy postmenopausal women in order to determine the effects of the increased brain activation on cognition and behavior. PMID:27676634

A functional thyrotropin- and growth hormone-secreting pituitary adenoma with a ultrastructurally monomorphic feature: a case study.

PubMed

Ozawa, Y; Kameya, T; Kasuga, A; Naritaka, H; Kanda, N; Maruyama, H; Saruta, T

1998-04-01

A 38-yr-old female with a TSH- and GH-secreting pituitary adenoma is described, who had both overt symptoms, hyperthyroidism and acromegaly. Her serum TSH was not suppressed despite high concentrations of free T3 and free T4, and her alpha-subunit/TSH molar ratio was high. Her serum GH was consistently high, and was not suppressed by an oral glucose tolerance test. Preoperative testing revealed that, although the TSH response was impaired, TSH, alpha-subunit and GH were increased by TRH injection, and that these hormones were reduced by bromocriptine or somatostatin analog. Although she did not have hyperprolactinemia, the in vitro culture and immunohistochemical studies revealed that the adenoma cells produced and released PRL, in addition to TSH, alpha-subunit and GH. Immunohistochemical studies showed the presence of GH in the cytoplasm of many adenoma cells. TSH beta-positive adenoma cells were less frequently seen than GH-positive adenoma cells. No cells showed the coexistence of GH and TSH beta, and a few cells were positive for PRL. By electron microscopy, the adenoma was found to be composed of a single cell type resembling thyrotrophs, and did not have any characteristics of somatotrophs. This case was considered to be of interest, because the adenoma was ultrastructurally monomorphous, but immunohistochemically polymorphous.

[High dose L-dopa infusion during general anesthesia for gastrectomy in a patient with parkinsonism].

PubMed

Horai, Tetsuya; Nishiyama, Tomoki; Yamamoto, Hirotoshi; Hanaoka, Kazuo

2002-01-01

A 68-year-old man with parkinsonism was scheduled for gastrectomy. Levodopa 1400 mg, droxidopa 300 mg and bromocriptine-mesylate 7.5 mg had been administered orally per day to control the symptom before surgery. On the day before surgery, oral medication was stopped and intravenous infusion of levodopa 100 mg.h-1 was started. Without any premedication but with levodopa infusion, anesthesia was induced with thiopental 175 mg and fentanyl 0.05 mg. Tracheal intubation was facilitated with vecuronium 6 mg and an epidural catheter was inserted. Anesthesia was maintained with O2, N2O and sevoflurane, combined with epidural block using mepivacaine. When blood pressure decreased, phenylephrine but not ephedrine was effective to increase blood pressure. Intravenous infusion of levodopa was continued for 19 days with decreasing doses from 8th postoperative day when injection of levodopa into the intestinal tube was started. On the 53rd day, he left the hospital without any complications. Serum concentrations of levodopa during and after surgery were 50 to 100 times higher than the therapeutic levels. However, he developed no complications, which suggests a wide safety range of levodopa. In conclusion, high dose levodopa infusion was effective in controlling the symptoms of Parkinsonism during general anesthesia.

Neuroleptic malignant syndrome developing after acute overdose with olanzapine and chlorpromazine.

PubMed

Morris, Enasio; Green, Digby; Graudins, Andis

2009-03-01

Neuroleptic malignant syndrome (NMS) is a relatively uncommon side effect that may develop after a recent increase in the therapeutic dose of an antipsychotic medication or the addition of a new agent in therapeutic doses. We report a case of NMS developing in a 36-year-old female patient 2 days following deliberate self-poisoning with 30 x 10-mg olanzapine tablets, 7 x 100-mg chlorpromazine tablets and an unknown amount of escitalopram. These were the patient's own medications. She had not been taking these for several weeks. The patient initially presented with sedation from her overdose which resolved over the next 24 hours. Following this, over the subsequent 24 hours, she became progressively confused, ataxic, hypertonic, ferbrile and tachycardic, with marked lead pipe rigidity of the limbs. Head CT, lumbar puncture and septic screen were all negative. She was treated with intravenous midazolam infusion, nasogastrically administered bromocriptine, external cooling and was mechanically ventilated. She gradually improved over a period of 10 days, with residual confusion lasting another week, and was discharged well with no deterioration from her premorbid neurologic state. To our knowledge, although there are numerous cases reported with therapeutic use, NMS has not been reported to develop following acute olanzapine overdose. Clinicians should be aware that this may be an uncommon side effect of antipsychotic medication.

Effect of dopamine agonist withdrawal after long-term therapy in prolactinomas. Studies with high-definition computerised tomography.

PubMed

Johnston, D G; Hall, K; Kendall-Taylor, P; Patrick, D; Watson, M; Cook, D B

1984-07-28

The clinical, radiological, and biochemical effects of dopamine agonist withdrawal after long-term treatment were investigated in seven women and eight men who had been treated for prolactinomas for 1.5 to 7 (mean 3.7) years. Before treatment, serum prolactin concentrations were 1473 to 115 000 mU/l, all patients had abnormal radiological findings, and six had suprasellar extensions of pituitary tumours. Treatment with either bromocriptine or pergolide relieved symptoms and suppressed prolactin secretion in most patients. The size of the residual tumour was defined by doing fourth generation computerised tomographic scans immediately before termination of therapy, and evidence of tumour re-expansion was sought on scans repeated 5-39 weeks later. After discontinuation of treatment, symptoms recurred in 13 of 15 patients and hyper-prolactinaemia redeveloped in 14. Other pituitary function tests remained unchanged or improved. In 13 of 15 patients tumour or gland size did not change after withdrawal of treatment. One man had a marginal increase in tumour size, while in another the pituitary tumour shrank. Thus, although cessation of long-term dopamine agonist therapy leads to recurrence of symptoms and hyperprolactinaemia, rapid tumour regrowth is uncommon and of small extent, and other pituitary function is not altered in the short term.

Stimulatory effect of clebopride on human prolactin secretion.

PubMed

Perez-Lopez, F R; Legido, A; Sisskin, M; Abos, M D

1980-11-01

Serum levels of prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in normally cycling women and normal men before and after oral admiministration of 1 mg of clebopride, a derivative of procainamide used in the treatment of gastrointestinal diseases. Clebopride produced a significant increase (P < 0.001) in serum PRL to a 6-fold peak as compared with basal levels. After 240 minutes the levels remained significantly higher (P < 0.05) than the mean basal level at -30 and 0 minutes. No significant effects of clebopride were noted upon the circulating levels of LH and FSH. The peak PRL response to clebopride was unaffected by pretreatment with 100 mg of nomifensine, although the secretory area from 120 to 210 minutes after clebopride was greater (P < 0.05) in the nomifensine-treated group than in the control experiment. When 5 mg of bromocriptine were given before clebopride, the PRL response was completely abolished as compared with the control experiment (P < 0.001). Our data provide new evidence that dopaminergic receptors of the adeylate cyclase system are involved in the regulation of PRL secretion, acting at the pituitary level rather than acting on the hypothalamus. The PRL-releasing activity of clebopride could be the explanation for the occasional menstrual disorders and galactorrhea registered in some cases of long-term treatment.

Pharmacological interventions for antisocial personality disorder

PubMed Central

Khalifa, Najat; Duggan, Conor; Stoffers, Jutta; Huband, Nick; Völlm, Birgit A; Ferriter, Michael; Lieb, Klaus

2014-01-01

Background Antisocial personality disorder (AsPD) is associated with a wide range of disturbance including persistent rule-breaking, criminality, substance misuse, unemployment, homelessness and relationship difficulties. Objectives To evaluate the potential beneficial and adverse effects of pharmacological interventions for people with AsPD. Search methods We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (1950 to September 2009), EMBASE (1980 to 2009, week 37), CINAHL (1982 to September 2009), PsycINFO (1872 to September 2009), ASSIA (1987 to September 2009), BIOSIS (1985 to September 2009), COPAC (September 2009), National Criminal Justice Reference Service Abstracts (1970 to July 2008), Sociological Abstracts (1963 to September 2009), ISI-Proceedings (1981 to September 2009), Science Citation Index (1981 to September 2009), Social Science Citation Index (1981 to September 2009), SIGLE (1980 to April 2006), Dissertation Abstracts (September 2009), ZETOC (September 2009) and the metaRegister of Controlled Trials (September 2009). Selection criteria Controlled trials in which participants with AsPD were randomly allocated to a pharmacological intervention and a placebo control condition. Two trials comparing one drug against another without a placebo control are reported separately. Data collection and analysis Three review authors independently selected studies. Two review authors independently extracted data. We calculated mean differences, with odds ratios for dichotomous data. Main results Eight studies met the inclusion criteria involving 394 participants with AsPD. Data were available from four studies involving 274 participants with AsPD. No study set out to recruit participants solely on the basis of having AsPD, and in only one study was the sample entirely of AsPD participants. Eight different drugs were examined in eight studies. Study quality was relatively poor. Inadequate reporting meant the data available were generally insufficient to allow any independent statistical analysis. The findings are limited to descriptive summaries based on analyses carried out and reported by the trial investigators. All the available data were derived from unreplicated single reports. Only three drugs (nortriptyline, bromocriptine, phenytoin) were effective compared to placebo in terms of improvement in at least one outcome. Nortriptyline was reported in one study as superior for men with alcohol dependency on mean number of drinking days and on alcohol dependence, but not for severity of alcohol misuse or on the patient’s or clinician’s rating of drinking. In the same study, both nortriptyline and bromocriptine were reported as superior to placebo on anxiety on one scale but not on another. In one study, phenytoin was reported as superior to placebo on the frequency and intensity of aggressive acts in male prisoners with impulsive (but not premeditated) aggression. In the remaining two studies, both amantadine and desipramine were not superior to placebo for adults with opioid and cocaine dependence, and desipramine was not superior to placebo for men with cocaine dependence. Authors’ conclusions The body of evidence summarised in this review is insufficient to allow any conclusion to be drawn about the use of pharmacological interventions in the treatment of antisocial personality disorder. PMID:20687091

In Vivo Evidence for Epidermal Growth Factor Receptor (EGFR)-mediated Release of Prolactin from the Pituitary Gland

PubMed Central

Dahlhoff, Maik; Blutke, Andreas; Wanke, Rüdiger; Wolf, Eckhard; Schneider, Marlon R.

2011-01-01

Members of the epidermal growth factor receptor (EGFR/ERBB) system are essential local regulators of mammary gland development and function. Emerging evidence suggests that EGFR signaling may also influence mammary gland activity indirectly by promoting the release of prolactin from the pituitary gland in a MAPK and estrogen receptor-α (ERα)-dependent manner. Here, we report that overexpression of the EGFR ligand betacellulin (BTC) causes a lactating-like phenotype in the mammary gland of virgin female mice including the major hallmarks of lactogenesis. BTC transgenic (BTC-tg) females showed reduced levels of prolactin in the pituitary gland and increased levels of the hormone in the circulation. Furthermore, treatment of BTC-tg females with bromocriptine, an inhibitor of prolactin secretion, blocked the development of the lactation-like phenotype, suggesting that it is caused by central release of prolactin rather than by local actions of BTC in the mammary gland. Introduction of the antimorphic Egfr allele Wa5 also blocked the appearance of the mammary gland alterations, revealing that the phenotype is EGFR-dependent. We detected an increase in MAPK activity, but unchanged phosphorylation of ERα in the pituitary gland of BTC-tg females as compared with control mice. These results provide the first functional evidence in vivo for a role of the EGFR system in regulating mammary gland activity by modulating prolactin release from the pituitary gland. PMID:21914800

D-1 and D-2 receptor blockade have additive cataleptic effects in mice, but receptor effects may interact in opposite ways.

PubMed

Klemm, W R; Block, H

1988-02-01

The dopaminergic role of D-1 and D-2 receptors in catalepsy was evaluated using drugs with preferential receptor affinities. The D-1 antagonist, SCH 23390, caused distinct catalepsy in mice at 1, 2, and 10 mg/kg, IP, but not at two lower doses. The selective D-1 blocker, molindone, also caused catalepsy at 5 and 10 mg/kg; and blockade of both receptor types produced additive cataleptogenic effects. Apomorphine (4 mg/kg), which is an agonist for both receptors, potentiated SCH 23390-induced catalepsy much more than it did the catalepsy induced by molindone; the potentiation was produced by higher, not lower, doses of apomorphine. To determine if the apomorphine potentiation was mediated by D-1 or D-2 receptors, we tested selective agonists in mice that were concurrently injected with selective blockers. SCH 23390-induced catalepsy was potentiated by a large dose of the D-2 agonist, bromocriptine. The catalepsy of D-2 blockade with molindone was not potentiated by the D-1 agonist, SKF 38393, which slightly disrupted the catalepsy of D-2 blockade. We conclude that catalepsy is not a simple D-2 blockade phenomenon and that preferential antagonism of either receptor type can cause catalepsy. Catalepsy is most profound when both receptor types are blocked. Dopamine agonists, in large concentrations, are known to promote movements, and thus it is not surprising that they tend to disrupt catalepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine monophosphate-activated protein kinase-based classification of diabetes pharmacotherapy

PubMed Central

Dutta, D; Kalra, S; Sharma, M

2017-01-01

The current classification of both diabetes and antidiabetes medication is complex, preventing a treating physician from choosing the most appropriate treatment for an individual patient, sometimes resulting in patient-drug mismatch. We propose a novel, simple systematic classification of drugs, based on their effect on adenosine monophosphate-activated protein kinase (AMPK). AMPK is the master regular of energy metabolism, an energy sensor, activated when cellular energy levels are low, resulting in activation of catabolic process, and inactivation of anabolic process, having a beneficial effect on glycemia in diabetes. This listing of drugs makes it easier for students and practitioners to analyze drug profiles and match them with patient requirements. It also facilitates choice of rational combinations, with complementary modes of action. Drugs are classified as stimulators, inhibitors, mixed action, possible action, and no action on AMPK activity. Metformin and glitazones are pure stimulators of AMPK. Incretin-based therapies have a mixed action on AMPK. Sulfonylureas either inhibit AMPK or have no effect on AMPK. Glycemic efficacy of alpha-glucosidase inhibitors, sodium glucose co-transporter-2 inhibitor, colesevelam, and bromocriptine may also involve AMPK activation, which warrants further evaluation. Berberine, salicylates, and resveratrol are newer promising agents in the management of diabetes, having well-documented evidence of AMPK stimulation medicated glycemic efficacy. Hence, AMPK-based classification of antidiabetes medications provides a holistic unifying understanding of pharmacotherapy in diabetes. This classification is flexible with a scope for inclusion of promising agents of future. PMID:27652986

Congenital gigantism due to growth hormone-releasing hormone excess and pituitary hyperplasia with adenomatous transformation.

PubMed

Zimmerman, D; Young, W F; Ebersold, M J; Scheithauer, B W; Kovacs, K; Horvath, E; Whitaker, M D; Eberhardt, N L; Downs, T R; Frohman, L A

1993-01-01

The cause of gigantism in most patients is a GH-secreting pituitary tumor. In this report, a case of congenital gigantism due to probable central hypersection of GH-releasing hormone (GHRH) is described. Normal at birth (4.4 kg; 53 cm), our 7-yr-old male patient grew progressively thereafter to attain a height of 182 cm and a weight of 99.4 kg at the time of our evaluation. The markedly increased baseline plasma levels of GH (730 micrograms/L) did not suppress during a standard 3-h oral glucose tolerance test, but did increase 54% after iv infusion of GHRH. Baseline plasma levels of insulin-like growth factor-I, PRL, and immunoreactive GHRH were also markedly increased. Computed imaging of the head showed a large, partially cystic sellar and suprasellar mass. Extensive imaging studies did not localize a potential source of GHRH. Preoperative treatment with octreotide and bromocriptine for 4 months resulted in a 25% reduction of suprasellar tissue mass. The pituitary tissue removed at transsphenoidal and transfrontal operations showed massive somatotroph, lactotroph, and mammosomatotroph hyperplasia. Areas of GH- and PRL-secreting cell adenomatous transformation were also evident. No histological or immunohistochemical evidence of a pituitary source of GHRH was found. The peripheral plasma immunoreactive GHRH concentration remained unaffected by pharmacological and surgical interventions. We suspect that a congenital hypothalamic regulatory defect may be responsible for the GHRH excess in this case.

Psychotic Symptoms Associated with the use of Dopaminergic Drugs, in Patients with Cocaine Dependence or Abuse.

PubMed

Roncero, Carlos; Abad, Alfonso C; Padilla-Mata, Antonio; Ros-Cucurull, Elena; Barral, Carmen; Casas, Miquel; Grau-López, Lara

2017-01-01

In the field of dual diagnosis, physicians are frequently presented with pharmacological questions. Questions about the risk of developing psychotic symptoms in cocaine users who need treatment with dopaminergic drugs could lead to an undertreatment. Review the presence of psychotic symptoms in patients with cocaine abuse/dependence, in treatment with dopaminergic drugs. Systematic PubMed searches were conducted including December 2014, using the keywords: "cocaine", dopaminergic drug ("disulfuram-methylphenidate-bupropion-bromocriptine-sibutramineapomorphine- caffeine") and ("psychosis-psychotic symptoms-delusional-paranoia"). Articles in English, Spanish, Portuguese, French, and Italian were included. Articles in which there was no history of cocaine abuse/dependence, absence of psychotic symptoms, systematic reviews, and animal studies, were excluded. 313 papers were reviewed. 7 articles fulfilled the inclusion-exclusion criteria. There is a clinical trial including 8 cocaine-dependent patients using disulfiram in which 3 of them presented psychotic symptoms and 6 case-reports: disulfuram (1), methylphenidate (1), disulfiram with methylphenidate (2), and bupropion (2), reporting psychotic symptoms, especially delusions of reference and persecutory ideation. Few cases have been described, which suggests that the appearance of these symptoms is infrequent. The synergy of dopaminergic effects or the dopaminergic sensitization in chronic consumption are the explanatory theories proposed by the authors. In these cases, a relationship was found between taking these drugs and the appearance of psychotic symptoms. Given the low number of studies found, further research is required. The risk of psychotic symptoms seems to be acceptable if we compare it with the benefits for the patients but a closer monitoring seems to be advisable.

Id1, Id2 and Id3 are induced in rat melanotrophs of the pituitary gland by dopamine suppression under continuous stress.

PubMed

Konishi, H; Ogawa, T; Nakagomi, S; Inoue, K; Tohyama, M; Kiyama, H

2010-09-15

In rats under continuous stress (CS) there is decreased hypothalamic dopaminergic innervation to the intermediate lobe (IL) of the pituitary gland, which causes hyperactivation and subsequent degeneration of melanotrophs in the IL. In this study, we investigated the molecular basis for the changes that occur in melanotrophs during CS. Using microarray analysis, we identified several genes differentially expressed in the IL under CS conditions. Among the genes up-regulated under CS conditions, we focused on the inhibitor of DNA binding/differentiation (Id) family of dominant negative basic helix-loop-helix (bHLH) transcription factors. RT-PCR, Western blotting and in situ hybridization confirmed the significant inductions of Id1, Id2 and Id3 in the IL of CS rats. Administration of the dopamine D2 receptor agonist bromocriptine prevented the inductions of Id1-3 in the IL of CS rats, whereas application of the dopamine D2 antagonist sulpiride induced significant expressions of Id1-3 in the IL of normal rats. Moreover, an in vitro study using primary cultured melanotrophs demonstrated a direct effect on Id1-3 inductions by dopamine suppression. These results suggest that the decreased dopamine levels in the IL during CS induce Id1-3 expressions in melanotrophs. Because Id family members inhibit various bHLH transcription factors, it is conceivable that the induced Id1-3 would cooperatively modulate gene expressions in melanotrophs under CS conditions to induce hormone secretion. (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Recruitment of β-arrestin2 to the dopamine D2 receptor: Insights into anti-psychotic and anti-parkinsonian drug receptor signaling

PubMed Central

Klewe, Ib V.; Nielsen, Søren M.; Tarpø, Louise; Urizar, Eneko; Dipace, Concetta; Javitch, Jonathan A.; Gether, Ulrik; Egebjerg, Jan; Christensen, Kenneth V.

2013-01-01

Drugs acting at dopamine D2-like receptors play a pivotal role in the treatment of both schizophrenia and Parkinson’s disease. Recent studies have demonstrated a role for G-protein independent D2 receptor signaling pathways acting through β-arrestin. In this study we describe the establishment of a Bioluminescence Resonance Energy Transfer (BRET) assay for measuring dopamine induced recruitment of human β-arrestin2 to the human dopamine D2 receptor. Dopamine, as well as the dopamine receptor agonists pramipexole and quinpirole, acted as full agonists in the assay as reflected by their ability to elicit marked concentration dependent increases in the BRET signal signifying β-arrestin2 recruitment to the D2 receptor. As expected from their effect on G-protein coupling and cAMP levels mediated through the D2 receptor RNPA, pergolide, apomorphine, ropinirole, bromocriptine, 3PPP, terguride, aripiprazole, SNPA all acted as partial agonists with decreasing efficacy in the BRET assay. In contrast, a wide selection of typical and atypical anti-psychotics was incapable of stimulating β-arrestin2 recruitment to the D2 receptor. Moreover, we observed that haloperidol, sertindole, olanzapine, clozapine and ziprasidone all fully inhibited the dopamine induced β-arrestin2 recruitment to D2 receptor (short variant) in a concentration dependent manner. We conclude that most anti-psychotics are incapable of stimulating β-arrestin2 recruitment to the dopamine D2 receptor, in accordance with their antagonistic properties at the level of G-protein coupling. PMID:18455202

Prolactinoma and pregnancy: From the wish of conception to lactation.

PubMed

Maiter, Dominique

2016-06-01

Prolactinoma is a common cause of infertility in young women and treatment with dopamine agonists (DA) allows restoration of fertility in over 90% of the cases. Both bromocriptine and cabergoline have shown a good safety profile when administered during early pregnancy. In particular, data on exposure of the fetus or embryo to cabergoline during the first weeks of pregnancy have now been reported in more than 900 cases, and do indicate that cabergoline is safe in this context. There is no increase in the frequency of spontaneous miscarriage, premature delivery, multiple births or neonatal malformations, and follow-up studies of the children for up to 12years after fetal exposure to cabergoline did not show any physical or developmental abnormalities. These women should therefore continue DA treatment until pregnancy has been initiated. Treatment discontinuation is recommended at that time in women with microprolactinoma or non-compressive macroprolactinoma. For microprolactinomas, the risk of symptomatic tumour enlargement during pregnancy is very low (2-3%). It is higher for macroprolactinomas (20-30%) and careful follow-up is advised, including MRI without contrast injection if symptoms or visual disturbances develop. If a symptomatic tumour enlargement does occur, reinitiation of the dopamine agonist (BRC or CAB) is indicated rather than surgery. Breast-feeding has no harmful effect on tumour growth and DA treatment, if still needed, may be postponed as long as breast-feeding is desired. Finally, about 40% of women with a microprolactinoma or an intermediate size macroprolactinoma may be in prolonged remission after one or more pregnancies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

General seizures revealing macro-adenomas secreting prolactin or prolactin and growth hormone in men

PubMed Central

Chentli, Farida; Akkache, Lina; Daffeur, Katia; Azzoug, Said

2014-01-01

Background: Epilepsy is a heterogeneous condition with numerous etiologies. Pituitary tumors are rarely responsible for generalized convulsions except when they are very large. Apart from anecdotic cases, only one study concerning epilepsy frequency in male macroprolactinomas is available in Medline. Our aim was to analyze epilepsy frequency and conditions under which seizures appear and disappear in men harboring macroprolactinomas or somatolactotroph adenomas. Materials and Methods: We retrospectively analyzed 90 men with macro-adenomas (>1 cm) secreting prolactin (PRL) (n = 82) or both PRL and growth hormone (n = 8) to look for generalized seizures. We took into account familial and personal medical history, clinical examination, routine and hormonal analyzes, and radiological assessment based on cerebral magnetic resonance imaging. Results: Between 1992 and 2012, we collected eight cases (8.9%): Seven were hospitalized for recent generalized seizures; one had epilepsy after conventional radiotherapy given in 1992 because of neurosurgery failure and resistance to bromocriptine. Their median age was 33.75 years (22-58), median PRL was 9,198 ng/ml and median tumor height was 74 mm (41-110). The temporal lobe was invaded in six cases. After tumor reduction, epilepsy disappeared and never relapsed after a follow-up varying between 1 and 20 years. Conclusion: Epilepsy, which is a life-threatening condition, can be the first presentation in men with prolactinomas or somatolactotroph adenomas, especially those involving the supra sellar area, and the brain. Convulsions can also appear after radiotherapy. That one should be avoided, if possible, before tumor reduction by surgery or medical treatment. PMID:24944932

Evidence-based guideline: treatment of tardive syndromes: report of the Guideline Development Subcommittee of the American Academy of Neurology.

PubMed

Bhidayasiri, Roongroj; Fahn, Stanley; Weiner, William J; Gronseth, Gary S; Sullivan, Kelly L; Zesiewicz, Theresa A

2013-07-30

To make evidence-based recommendations regarding management of tardive syndromes (TDS), including tardive dyskinesias (TDD), by addressing 5 questions: 1) Is withdrawal of dopamine receptor blocking agents (DRBAs) an effective TDS treatment? 2) Does switching from typical to atypical DRBAs reduce TDS symptoms? 3) What is the efficacy of pharmacologic agents in treating TDS? 4) Do patients with TDS benefit from chemodenervation with botulinum toxin? 5) Do patients with TDS benefit from surgical therapy? PsycINFO, Ovid MEDLINE, EMBASE, Web of Science, and Cochrane were searched (1966-2011). Articles were classified according to a 4-tiered evidence-rating scheme; recommendations were tied to the evidence. Clonazepam probably improves TDD and ginkgo biloba probably improves TDS (both Level B); both should be considered as treatment. Risperidone may improve TDS but cannot be recommended as treatment because neuroleptics may cause TDS despite masking symptoms. Amantadine and tetrabenazine might be considered as TDS treatment (Level C). Diltiazem should not be considered as TDD treatment (Level B); galantamine and eicosapentaenoic acid may not be considered as treatment (Level C). Data are insufficient to support or refute use of acetazolamide, bromocriptine, thiamine, baclofen, vitamin E, vitamin B6, selegiline, clozapine, olanzapine, melatonin, nifedipine, fluperlapine, sulpiride, flupenthixol, thiopropazate, haloperidol, levetiracetam, quetiapine, ziprasidone, sertindole, aripiprazole, buspirone, yi-gan san, biperiden discontinuation, botulinum toxin type A, electroconvulsive therapy, α-methyldopa, reserpine, and pallidal deep brain stimulation as TDS treatments (Level U). Data are insufficient to support or refute TDS treatment by withdrawing causative agents or switching from typical to atypical DRBA (Level U).

Activation of neurotensin receptor type 1 attenuates locomotor activity.

PubMed

Vadnie, Chelsea A; Hinton, David J; Choi, Sun; Choi, YuBin; Ruby, Christina L; Oliveros, Alfredo; Prieto, Miguel L; Park, Jun Hyun; Choi, Doo-Sup

2014-10-01

Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF-81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lowering prolactin reduces post-hatch parental care in male and female zebra finches (Taeniopygia guttata).

PubMed

Smiley, Kristina O; Adkins-Regan, Elizabeth

2018-02-01

Parental care is a widespread phenomenon observed in many diverse taxa. Neuroendocrine systems have long been thought to play an important role in stimulating the onset of parental behavior. In most birds with altricial young, circulating prolactin (PRL) levels are low during non-breeding times and significantly increase during late incubation and early post-hatch chick care. Because of this pattern, PRL has been suggested to be involved in the initiation of parental care in birds, but rarely has this hypothesis been causally tested. To begin testing the hypothesis, we inhibited the release of endogenous PRL with bromocriptine (BR) on the 3days prior to hatching in incubating parents and the first 2days of post-hatch care, when PRL was found to be highest in zebra finches. Nest temperatures were recorded during all 5days and parental behavior was recorded on days 1-2 post-hatch. In addition to hormonal systems, reproductive experience may also influence parental care; therefore, we tested age-matched inexperienced and experienced pairs in each group. BR either eliminated or drastically reduced chick brooding and feeding behavior, resulting in decreased nest temperatures on days 1 and 2 post-hatch. Experienced control birds fed chicks more than inexperienced birds and control females fed more than males. Chick feeding behavior was positively correlated in control male-female pairs, but not in BR pairs. This is one of the few causal studies to demonstrate that PRL is necessary for post-hatch care in a biparental songbird, and is the first to show this effect in zebra finches. Copyright © 2017 Elsevier Inc. All rights reserved.

Height, shape and anterior-posterior diameter of pituitary gland on magnetic resonance imaging among patients with multiple sclerosis compared to normal individuals.

PubMed

Saba, Mohammad; Ebrahimi, Hossein Ali; Ahmadi-Pour, Habibeh; Khodadoust, Mohammad

2017-10-07

Background: Several studies indicate contribution of hypothalamus-pituitary-adrenal (HPA) axis in multiple sclerosis (MS) disease. This study was designed to determine whether there is an effective difference in pituitary height, shape, and anterior-posterior diameter (APD) between patients with MS and the control group. Methods: In this study, sagittal pituitary height and APD of 134 men and women (64 patients with MS and 70 healthy subjects as control group) were measured by T1 sequence magnetic resonance imaging (MRI). All the subjects were free of sellar or parasellar pathology without a history of surgical intervention or prolactin affecting drugs like bromocriptine and cabergoline or corticosteroid consumption. Results: Mean height of pituitary gland was 6.62 ± 1.43 and 5.78 ± 1.15 mm for patients and the control group, respectively, and the difference between the two groups was statistically significant (P = 0.001). Mean APD was 10.40 ± 1.29 mm for the group of patients and 10.25 ± 1.41 mm for the control group, respectively, without significant differences. 46.9%, 37.5%, and 15.6% of patients had flat, convex, and concave hypophyseal surfaces, respectively. This rate was 50%, 30%, and 20% among the control group, respectively. There was no significant difference between our measurements among patients on whom imaging study was performed at time of disease onset with others. Conclusion: Mean height of pituitary gland among patients with MS was significantly greater than the control group (P = 0.001). So can we consider the same etiology for pituitary hypertrophy among patients with MS as a hypothesis?

"Hyperglutamatergic cortico-striato-thalamo-cortical circuit" breaker drugs alleviate tics in a transgenic circuit model of Tourette׳s syndrome.

PubMed

Nordstrom, Eric J; Bittner, Katie C; McGrath, Michael J; Parks, Clinton R; Burton, Frank H

2015-12-10

The brain circuits underlying tics in Tourette׳s syndrome (TS) are unknown but thought to involve cortico/amygdalo-striato-thalamo-cortical (CSTC) loop hyperactivity. We previously engineered a transgenic mouse "circuit model" of TS by expressing an artificial neuropotentiating transgene (encoding the cAMP-elevating, intracellular A1 subunit of cholera toxin) within a small population of dopamine D1 receptor-expressing somatosensory cortical and limbic neurons that hyperactivate cortico/amygdalostriatal glutamatergic output circuits thought to be hyperactive in TS and comorbid obsessive-compulsive (OC) disorders. As in TS, these D1CT-7 ("Ticcy") transgenic mice׳s tics were alleviated by the TS drugs clonidine and dopamine D2 receptor antagonists; and their chronic glutamate-excited striatal motor output was unbalanced toward hyperactivity of the motoric direct pathway and inactivity of the cataleptic indirect pathway. Here we have examined whether these mice׳s tics are countered by drugs that "break" sequential elements of their hyperactive cortical/amygdalar glutamatergic and efferent striatal circuit: anti-serotonoceptive and anti-noradrenoceptive corticostriatal glutamate output blockers (the serotonin 5-HT2a,c receptor antagonist ritanserin and the NE alpha-1 receptor antagonist prazosin); agmatinergic striatothalamic GABA output blockers (the presynaptic agmatine/imidazoline I1 receptor agonist moxonidine); and nigrostriatal dopamine output blockers (the presynaptic D2 receptor agonist bromocriptine). Each drug class alleviates tics in the Ticcy mice, suggesting a hyperglutamatergic CSTC "tic circuit" could exist in TS wherein cortical/amygdalar pyramidal projection neurons׳ glutamatergic overexcitation of both striatal output neurons and nigrostriatal dopaminergic modulatory neurons unbalances their circuit integration to excite striatothalamic output and create tics, and illuminating new TS drug strategies. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Current and Emerging Pharmacotherapies for Cessation of Tobacco Smoking.

PubMed

Gómez-Coronado, Nieves; Walker, Adam J; Berk, Michael; Dodd, Seetal

2018-02-01

Tobacco use disorder is a chronic illness. With its high comorbidity rate, it is a major cause of years of life lost or years lived with disability; however, it is also considered the most preventable cause of death in developed countries. Since the development of nicotine replacement therapy (NRT) in 1978, treatment options have continued to evolve and expand. Despite this, currently available treatments remain insufficient, with less than 25% of smokers remaining abstinent 1 year after treatment. In this article, we review existing and emerging smoking cessation pharmacotherapies, with a special emphasis on the most promising agents that are currently being investigated. A search of the Cochrane Database of Systematic Reviews and the PubMed, Ovid, and ClinicalTrials.gov databases (August 2 to September 1, 2017) was undertaken for articles on smoking cessation pharmacotherapies, applying no language restrictions. More than 40 pharmacotherapies were reviewed including conventional pharmacotherapies-NRT, bupropion, and varenicline (all approved by the U.S. Food and Drug Administration as first-line treatment of smoking cessation)-and novel therapies: cytisine, N-acetylcysteine, cycloserine, memantine, baclofen, topiramate, galantamine, and bromocriptine. Studies of combination NRT and varenicline showed the greatest smoking cessation rates. Clonidine and nortriptyline are second-line treatments used when first-line treatments fail or are contraindicated, or by patient preference. Some novel therapies, especially acetylcholinesterase inhibitors, cytisine, and N-acetylcysteine, display promising results. Because the results of randomized clinical trials were reported using varied end points and outcome measures, direct comparisons between different pharmacotherapies cannot easily be evaluated. Additional high-quality randomized double-blind placebo-controlled trials with long-term follow-up, using validated sustained abstinence measures, are needed to find more effective smoking cessation aids. © 2017 Pharmacotherapy Publications, Inc.

Are there differential symptom profiles that improve in response to different pharmacological treatments of premenstrual syndrome/premenstrual dysphoric disorder?

PubMed

Halbreich, Uriel; O'Brien, P M Shaughn; Eriksson, Elias; Bäckström, Torbjörn; Yonkers, Kimberly A; Freeman, Ellen W

2006-01-01

Current evidence suggests that the accepted treatments for premenstrual syndrome (PMS)/premenstrual dysphoric disorder (PMDD) have similar overall efficacy. While these treatments are more effective than placebo, response rates associated with them are far from satisfactory (<60%), such that, irrespective of treatment modality, there remain a significant number of women who are unresponsive to current conventional pharmacological therapy. The available data on response rates of specific types of premenstrual symptoms to, or symptom profiles that are most amenable to, each treatment modality are limited and not well defined because most studies were not designed to assess specific symptom profiles. Those studies that have attempted to evaluate which symptom profiles respond to specific therapies have revealed variations within the individual modalities, as well as between the different modalities. It appears that suppression of ovulation ameliorates a broad range of behavioural as well as physical premenstrual symptoms. SSRIs are most effective for irritability and anxiety symptoms, with lesser efficacy for 'atypical' premenstrual symptoms. GABAergic compounds are most efficacious for anxiety and anxious/depressive symptoms, while dopamine agonists, particularly bromocriptine, are perhaps most efficacious for mastalgia. Overall treatment response rates may improve if treatments are targeted at well-defined subgroups of patients. Re-analysis of available datasets from randomised clinical trials may shed more light on the notion that targeting women with specific premenstrual symptom profiles for specific treatment modalities would improve response rates beyond the current ceiling of approximately 60%. Such information would also improve understanding of the putative pathophysiological mechanisms underlying PMS and PMDD, and may point to a more specific diagnosis of these conditions.

Treatment of restless legs syndrome: Evidence-based review and implications for clinical practice (Revised 2017)§.

PubMed

Winkelmann, Juliane; Allen, Richard P; Högl, Birgit; Inoue, Yuichi; Oertel, Wolfgang; Salminen, Aaro V; Winkelman, John W; Trenkwalder, Claudia; Sampaio, Cristina

2018-05-14

The objective of the current review was to update the previous evidence-based medicine review of treatments for restless legs syndrome published in 2008. All randomized, controlled trials (level I) with a high quality score published between January 2007 and January 2017 were reviewed. Forty new studies qualified for efficacy review. Pregabalin, gabapentin enacarbil, and oxycodone/naloxone, which did not appear in the previous review, have accrued data to be considered efficacious. Likewise, new data enable the modification of the level of efficacy for rotigotine from likely efficacious to efficacious. Intravenous ferric carboxymaltose and pneumatic compression devices are considered likely efficacious in idiopathic restless legs syndrome. Bupropion and clonidine were reviewed, but the lack of data determined a rating of insufficient evidence for efficacy. The following interventions continue to be considered efficacious as in 2008: levodopa, ropinirole, pramipexole, cabergoline, pergolide, and gabapentin. Bromocriptine, oxycodone, carbamazepine, and valproic acid are considered likely efficacious. Oral iron is nonefficacious in iron-sufficient subjects, but its benefit for patients with low peripheral iron status has not been adequately evaluated. Restless legs syndrome augmentation has been identified as a significant long-term treatment complication for pramipexole more than pregabalin and possibly for all dopaminergic agents more than α2δ ligands. Therefore, special monitoring for augmentation is required for all dopaminergic medications as well as tramadol. Other drugs also require special safety monitoring: cabergoline, pergolide, oxycodone, methadone, tramadol, carbamazepine, and valproic acid. Finally, we also highlighted gaps and needs for future clinical research and studies of restless legs syndrome. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Has the mammary gland a protective mechanism against overexposure to triiodothyronine during the peripartum period? The prolactin pulse down-regulates mammary type I deiodinase responsiveness to norepinephrine.

PubMed

Anguiano, B; Rojas-Huidobro, R; Delgado, G; Aceves, C

2004-11-01

Peripartum is a crucial period for mammary gland final differentiation and the onset of lactation. Although the 'trigger' for lactogenesis depends on several hormones, a key factor is the peripartum prolactin (PRL) pulse whose deletion results in a failure to initiate milk production. Other hormones having a critical role during this period but exerting a contrary effect are the thyronines. A transitory hypothyroidism occurs at peripartum in serum and several other extrathyroidal tissues, whereas the induction of hyperthyroidism during late pregnancy is associated with the absence of lactation after delivery. We analyzed the mammary gland during pregnancy and lactation for: (a) the type and amount of thyroid receptors (TRs), (b) the local triiodothyronine (T3) generation catalyzed by type I deiodinase (Dio1), (c) the Dio1 response to norepinephrine (NE) and (d) the effect on Dio1 and TRs of blocking the PRL pulse at peripartum. Our data showed that during pregnancy the mammary gland contains Dio1 in low amounts associated with the highest expression of TRalpha1; whereas during lactation the gland shows high levels of both Dio1 and TRalpha1. However, at peripartum, both TRs and Dio1 decrease, and Dio1 becomes refractory to NE. This refractoriness disappears when the PRL pulse is blocked by the dopamine agonist bromocriptine. This blockade is also accompanied by a significant decrease in cyclin D1 expression. Our data suggested that the peripartum PRL pulse is part of a protective mechanism against precocious differentiation and/or premature involution of the alveolar epithelium due to T3 overexposure.

Lysergic acid diethylamide (LSD) is a partial agonist of D2 dopaminergic receptors and it potentiates dopamine-mediated prolactin secretion in lactotrophs in vitro.

PubMed

Giacomelli, S; Palmery, M; Romanelli, L; Cheng, C Y; Silvestrini, B

1998-01-01

The hallucinogenic effects of lysergic acid diethylamide (LSD) have mainly been attributed to the interaction of this drug with the serotoninergic system, but it seems more likely that they are the result of the complex interactions of the drug with both the serotoninergic and dopaminergic systems. The aim of the present study was to investigate the functional actions of LSD at dopaminergic receptors using prolactin secretion by primary cultures of rat pituitary cells as a model. LSD produced a dose-dependent inhibition of prolactin secretion in vitro with an IC50 at 1.7x10(-9) M. This action was antagonized by spiperone but not by SKF83566 or cyproheptadine, which indicates that LSD has a specific effect on D2 dopaminergic receptors. The maximum inhibition of prolactin secretion achieved by LSD was lower than that by dopamine (60% versus 80%). Moreover, the fact that LSD at 10(-8)-10(-6) M antagonized the inhibitory effect of dopamine (10(-7) M) and bromocriptine (10(-11) M) suggests that LSD acts as a partial agonist at D2 receptors on lactotrophs in vitro. Interestingly, LSD at 10(-13)-10(-10) M, the concentrations which are 10-1000-fold lower than those required to induce direct inhibition on pituitary prolactin secretion, potentiated the dopamine (10(-10)-2.5x10(-9) M)-mediated prolactin secretion by pituitary cells in vitro. These results suggest that LSD not only interacts with dopaminergic receptors but also has a unique capacity for modulating dopaminergic transmission. These findings may offer new insights into the hallucinogenic effect of LSD.

Development of pituitary adenoma in women with hyperprolactinaemia: clinical, endocrine, and radiological characteristics.

PubMed Central

Pontiroli, A E; Falsetti, L

1984-01-01

Sixty eight women referred for treatment of hyperprolactinaemia entered a three year follow up study to determine the clinical and endocrine course of the disease and its association with microadenoma of the pituitary. Details recorded before treatment included medical history, gonadotrophin and ovarian hormonal concentrations, and release of prolactin in response to protirelin (thyrotrophin releasing hormone), benserazide, cimetidine, and nomifensine. Sellar tomography was then performed yearly for three years in all women, 54 of them also undergoing computed coronal and sagittal tomography. At baseline evaluation 27 women showed radiological evidence of pituitary adenoma; at the end of the follow up period the number had increased to 41. Amenorrhoea, steady and raised serum prolactin concentrations, a low ratio of luteinising hormone to follicle stimulating hormone, a longer duration of disease, and low serum progesterone concentrations were more common in women with a final diagnosis of pituitary adenoma than in those whose sella remained normal. Tests for release of prolactin had yielded abnormal results from the outset in all 41 women with radiological evidence of pituitary adenoma and in about half of those whose sella had remained radiologically normal. Response to medical treatment (metergoline in 20 patients, bromocriptine in 21) was similar and showed no difference between patients with tumorous and non-tumorous hyperprolactinaemia. These findings suggest that a large proportion of women with hyperprolactinaemia may harbour a prolactin secreting pituitary adenoma which becomes apparent over a relatively short period. Amenorrhoea and steady and raised serum prolactin concentrations are more common in these women. Tests for release of prolactin are of predictive value in identifying women who will develop a pituitary adenoma. PMID:6421360

Glycyrrhetinic acid and E.resveratroloside act as potential plant derived compounds against dopamine receptor D3 for Parkinson’s disease: a pharmacoinformatics study

PubMed Central

Mirza, Muhammad Usman; Mirza, A Hammad; Ghori, Noor-Ul-Huda; Ferdous, Saba

2015-01-01

Parkinson’s disease (PD) is caused by loss in nigrostriatal dopaminergic neurons and is ranked as the second most common neurodegenerative disorder. Dopamine receptor D3 is considered as a potential target in drug development against PD because of its lesser side effects and higher degree of neuro-protection. One of the prominent therapies currently available for PD is the use of dopamine agonists which mimic the natural action of dopamine in the brain and stimulate dopamine receptors directly. Unfortunately, use of these pharmacological therapies such as bromocriptine, apomorphine, and ropinirole provides only temporary relief of the disease symptoms and is frequently linked with insomnia, anxiety, depression, and agitation. Thus, there is a need for an alternative treatment that not only hinders neurodegeneration, but also has few or no side effects. Since the past decade, much attention has been given to exploitation of phytochemicals and their use in alternative medicine research. This is because plants are a cheap, indispensable, and never ending resource of active compounds that are beneficial against various diseases. In the current study, 40 active phytochemicals against PD were selected through literature survey. These ligands were docked with dopamine receptor D3 using AutoDock and AutoDockVina. Binding energies were compared to docking results of drugs approved by the US Food and Drug Administration against PD. The compounds were further analyzed for their absorption, distribution, metabolism, and excretion-toxicity profile. From the study it is concluded that glycyrrhetinic acid and E.resveratroloside are potent compounds having high binding energies which should be considered as potential lead compounds for drug development against PD. PMID:25565772

Glycyrrhetinic acid and E.resveratroloside act as potential plant derived compounds against dopamine receptor D3 for Parkinson's disease: a pharmacoinformatics study.

PubMed

Mirza, Muhammad Usman; Mirza, A Hammad; Ghori, Noor-Ul-Huda; Ferdous, Saba

2015-01-01

Parkinson's disease (PD) is caused by loss in nigrostriatal dopaminergic neurons and is ranked as the second most common neurodegenerative disorder. Dopamine receptor D3 is considered as a potential target in drug development against PD because of its lesser side effects and higher degree of neuro-protection. One of the prominent therapies currently available for PD is the use of dopamine agonists which mimic the natural action of dopamine in the brain and stimulate dopamine receptors directly. Unfortunately, use of these pharmacological therapies such as bromocriptine, apomorphine, and ropinirole provides only temporary relief of the disease symptoms and is frequently linked with insomnia, anxiety, depression, and agitation. Thus, there is a need for an alternative treatment that not only hinders neurodegeneration, but also has few or no side effects. Since the past decade, much attention has been given to exploitation of phytochemicals and their use in alternative medicine research. This is because plants are a cheap, indispensable, and never ending resource of active compounds that are beneficial against various diseases. In the current study, 40 active phytochemicals against PD were selected through literature survey. These ligands were docked with dopamine receptor D3 using AutoDock and AutoDockVina. Binding energies were compared to docking results of drugs approved by the US Food and Drug Administration against PD. The compounds were further analyzed for their absorption, distribution, metabolism, and excretion-toxicity profile. From the study it is concluded that glycyrrhetinic acid and E.resveratroloside are potent compounds having high binding energies which should be considered as potential lead compounds for drug development against PD.

Activation of the dopamine receptor type-2 (DRD2) promoter by 9-cis retinoic acid in a cellular model of Cushing's disease mediates the inhibition of cell proliferation and ACTH secretion without a complete corticotroph-to-melanotroph transdifferentiation.

PubMed

Occhi, Gianluca; Regazzo, Daniela; Albiger, Nora Maria; Ceccato, Filippo; Ferasin, Sergio; Scanarini, Massimo; Denaro, Luca; Cosma, Chiara; Plebani, Mario; Cassarino, Maria Francesca; Mantovani, Giovanna; Stalla, Günter K; Pecori Giraldi, Francesca; Paez-Pareda, Marcelo; Scaroni, Carla

2014-09-01

Cushing's disease (CD) is a rare condition in which hypercortisolemia is secondary to excessive ACTH release from a pituitary corticotroph adenoma. CD is associated with significant morbidity and mortality, and a safe therapy that effectively targets the pituitary tumor is still lacking. Retinoic acid (RA) and dopamine agonists (DAs) have recently been considered as monotherapy in CD patients, and satisfactory results have been reported, albeit in a limited number of patients. Given the permissive role of RA on the dopamine receptor type-2 (DRD2), the aim of the present study was to see whether a combination of 9-cis RA and the DA bromocriptine (Br) might represent a possible treatment for CD. Here we show that 9-cis RA induces a functional DRD2 in the pituitary corticotroph cell line AtT20, and increases cell sensitivity to Br via a mechanism only partially related to corticotroph-to-melanotroph transdifferentiation. In addition, 9-cis RA and Br act synergistically to modulate cell viability, with favorable implications for clinical use. In nearly 45% of corticotropinoma-derived primary cultures, the combined administration of 9-cis RA and Br lowered the steady-state level of the ACTH precursor proopiomelanocortin (POMC) more efficiently than either of the drugs alone. In conclusion, the effects of a combination of 9-cis RA and Br on ACTH synthesis/secretion and cell viability in AtT20, and on POMC transcriptional activity in human corticotropinomas might represent a suitable starting point for assessing the potential of this treatment regimen for ACTH-secreting pituitary adenomas. This study thus has potentially important implications for novel therapeutic approaches to CD.

Characterization of the discriminative stimulus produced by the dopamine antagonist tiapride.

PubMed

Cohen, C; Sanger, D J; Perrault, G

1997-11-01

The ability of tiapride, a selective D2/D3 dopamine receptor antagonist, to exert discriminative stimulus control of responding was investigated by training rats to discriminate this drug (30 mg/kg) from saline in a two-lever, food-reinforcement procedure. Acquisition of tiapride discrimination required a relatively lengthy training period (mean of 76 sessions) but stable performance was maintained throughout the 18- month study. The dose of tiapride eliciting 50% tiapride-lever choice (ED50) was 2.2 mg/kg. After determination of the dose-effect curve with tiapride, substitution tests with several dopamine antagonists and other reference compounds were performed. All dopamine antagonists, including amisulpride (ED50 4 mg/kg), sulpiride (18 mg/kg), sultopride (1.5 mg/kg), clebopride (0.13 mg/kg), raclopride (0.16 mg/kg), metoclopramide (1.4 mg/kg), remoxipride (4.8 mg/kg), pimozide (2.7 mg/kg), thioridazine (3.4 mg/kg), olanzapine (0.97 mg/kg), chlorpromazine (1.9 mg/kg), risperidone (0.22 mg/kg) and haloperidol (0.14 mg/kg), except clozapine (>10 mg/kg), produced dose-dependent substitution for tiapride. Tiapride-like stimulus effects were observed at doses that decreased response rates. However, ED50 values for substitution by tiapride, amisulpride, sulpiride, sultopride, pimozide, clebopride and thioridazine were lower than ED50 values for decreasing responding. Additional studies were conducted to evaluate the ability of direct and indirect dopamine agonists to attenuate the tiapride discriminative stimulus. Pretreatment with d-amphetamine and nomifensine antagonized the discriminative stimulus effects of tiapride. Quinpirole, 7-OH-DPAT, bromocriptine and apomorphine partially blocked the stimulus effects of tiapride whereas SKF 38393 did not affect the discrimination. These results from substitution and antagonism tests indicated that the discriminative effects of tiapride are mediated by activity at D2/D3 dopamine receptors.

Pathologic hyperprolactinemia.

PubMed

Molitch, M E

1992-12-01

Unlike other pituitary hormones, PRL is under tonic inhibition by the hypothalamus by way of the PRL inhibitory factor, dopamine. GAP and GABA may also be inhibitory. PRL-releasing factors include TRH and VIP and possibly others. Circulating PRL is predominantly monomeric, although some patients with hyperprolactinemia appear to have increased quantities of the less biologically active polymeric forms. PRL is secreted episodically, with an increase in the amplitude of the secretory pulses with sleep. A transitory increase also occurs in response to the protein component of meals. Basal PRL levels increase in response to the hormonal milieu of pregnancy, and suckling postpartum triggers PRL release. Pathologic increases of PRL owing to hypothalamic dysregulation occur with a variety of medications, including the neuroleptics, metoclopramide, antidepressants, methyldopa, reserpine and verapamil, abuse of opiates and cocaine, renal insufficiency, cirrhosis, hypothyroidism, adrenal insufficiency, neurogenic stimulation, and idiopathically. Hyperprolactinemia also may occur from structural lesions of the stalk and hypothalamus, which cause disinhibition with or without maintenance of PRF activity, ectopic neoplasm production, and, most commonly, from prolactinomas. Diagnostic testing consists of routine chemistry and thyroid testing and imaging with MRI or CT. Dopamine agonists are the treatment of choice of prolactinomas of all sizes. Transsphenoidal surgery is an alternative for the patient who does not respond to medical therapy or who wishes definitive tumor removal, realizing that long-term cure is achieved in only 50% to 60% of patients with microadenomas and a much lower number in those with macroadenomas. Radiotherapy is reserved for patients who do respond to either medical or surgical treatment. Patients wishing to become pregnant usually are treated with bromocriptine, although prepregnancy surgical debulking may be advisable for those with large macroadenomas to reduce problems with tumor enlargement.

Levodopa delivery systems: advancements in delivery of the gold standard.

PubMed

Ngwuluka, Ndidi; Pillay, Viness; Du Toit, Lisa C; Ndesendo, Valence; Choonara, Yahya; Modi, Girish; Naidoo, Dinesh

2010-02-01

Despite the fact that Parkinson's disease (PD) was discovered almost 200 years ago, its treatment and management remain immense challenges because progressive loss of dopaminergic nigral neurons, motor complications experienced by the patients as the disease progresses and drawbacks of pharmacotherapeutic management still persist. Various therapeutic agents have been used in the management of PD, including levodopa (l-DOPA), selegiline, amantadine, bromocriptine, entacapone, pramipexole dihydrochloride and more recently istradefylline and rasagiline. Of all agents, l-DOPA although the oldest, remains the most effective. l-DOPA is easier to administer, better tolerated, less expensive and is required by almost all PD patients. However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels. Significant strides have been made to improve the delivery of l-DOPA in order to enhance its bioavailability and reduce plasma fluctuations as well as motor complications experienced by patients purportedly resulting from pulsatile stimulation of the striatal dopamine receptors. Drug delivery systems that have been instituted for the delivery of l-DOPA include immediate release formulations, liquid formulations, dispersible tablets, controlled release formulations, dual-release formulations, microspheres, infusion and transdermal delivery, among others. In this review, the l-DOPA-loaded drug delivery systems developed over the past three decades are elaborated. The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated. This review highlights the fact that neuropharmaceutics is at a precipice, which is expected to spur investigators to take that leap to enable the generation of innovative delivery systems for the effective management of PD.

Dopamine D2 receptor signaling modulates mutant ataxin-1 S776 phosphorylation and aggregation.

PubMed

Hearst, Scoty M; Lopez, Mariper E; Shao, Qingmei; Liu, Yong; Vig, Parminder J S

2010-08-01

Spinocerebellar ataxia 1 (SCA1) is a dominantly inherited neurodegenerative disease associated with progressive ataxia resulting from the loss of cerebellar Purkinje cells (PCs) and neurons in the brainstem. In PCs of SCA1 transgenic mice, the disease causing ataxin-1 protein mediates the formation of S100B containing cytoplasmic vacuoles and further self-aggregates to form intranuclear inclusions. The exact function of the ataxin-1 protein is not fully understood. However, the aggregation and neurotoxicity of the mutant ataxin-1 protein is dependent on the phosphorylation at serine 776 (S776). Although protein kinase A (PKA) has been implicated as the S776 kinase, the mechanism of PKA/ataxin-1 regulation in SCA1 is still not clear. We propose that a dopamine D(2) receptor (D2R)/S100B pathway may be involved in modulating PKA activity in PCs. Using a D2R/S100B HEK stable cell line transiently transfected with GFP-ataxin-1[82Q], we demonstrate that stimulation of the D2R/S100B pathway caused a reduction in mutant ataxin-1 S776 phosphorylation and ataxin-1 aggregation. Activation of PKA by forskolin resulted in an enhanced S776 phosphorylation and increased ataxin-1 nuclear aggregation, which was suppressed by treatment with D2R agonist bromocriptine and PKA inhibitor H89. Furthermore, treating SCA1 transgenic PC slice cultures with forskolin induced neurodegenerative morphological abnormalities in PC dendrites consistent with those observed in vivo. Taken together our data support a mechanism where PKA dependent mutant ataxin-1 phosphorylation and aggregation can be regulated by D2R/S100B signaling.

Dopamine D2 Receptor Signaling Modulates Mutant Ataxin-1 S776 Phosphorylation and Aggregation

PubMed Central

Hearst, SM; Lopez, ME; Shao, Q; Liu, Y; Vig, PJS

2010-01-01

Spinocerebellar ataxia 1 (SCA1) is a dominantly inherited neurodegenerative disease associated with progressive ataxia resulting from the loss of cerebellar Purkinje cells (PCs) and neurons in the brainstem. In PCs of SCA1 transgenic (Tg) mice, the disease causing ataxin-1 protein mediates the formation of S100B containing cytoplasmic vacuoles and further self-aggregates to form intranuclear inclusions. The exact function of the ataxin-1 protein is not fully understood. However, the aggregation and neurotoxicity of the mutant ataxin-1 protein is dependent on the phosphorylation at serine 776 (S776). Although protein kinase A (PKA) has been implicated as the S776 kinase, the mechanism of PKA/ataxin-1 regulation in SCA1 is still not clear. We propose that a dopamine D2 receptor (D2R)/S100B pathway may be involved in modulating PKA activity in PCs. Using a D2R/S100B HEK stable cell line transiently transfected with GFP-ataxin-1[82Q], we demonstrate that stimulation of the D2R/S100B pathway caused a reduction in mutant ataxin-1 S776 phosphorylation and ataxin-1 aggregation. Activation of PKA by forskolin resulted in an enhanced S776 phosphorylation and increased ataxin-1 nuclear aggregation, which was suppressed by treatment with D2R agonist bromocriptine and PKA inhibitor H89. Furthermore, treating SCA1 Tg PC slice cultures with forskolin induced neurodegenerative morphological abnormalities in PC dendrites consistent with those observed in vivo. Taken together our data support a mechanism where PKA dependent mutant ataxin-1 phosphorylation and aggregation can be regulated by D2R/S100B signaling. PMID:20477910

Activation of Neurotensin Receptor Type 1 Attenuates Locomotor Activity

PubMed Central

Vadnie, Chelsea A.; Hinton, David J.; Choi, Sun; Choi, YuBin; Ruby, Christina L.; Oliveros, Alfredo; Prieto, Miguel L.; Park, Jun Hyun; Choi, Doo-Sup

2014-01-01

Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders. PMID:24929110

Detection and management of the neuroleptic malignant syndrome.

PubMed

Bond, W S

1984-01-01

Two patients who developed the neuroleptic malignant syndrome (NMS) are described, and pertinent literature is reviewed. A 30-year-old man developed NMS, apparently as a result of haloperidol treatment of chronic undifferentiated schizophrenia. Treatment with cooling blankets, acetaminophen, dantrolene sodium, and bromocriptine mesylate decreased abnormal vital signs, but catatonia continued. After 30 treatments with electroconvulsive therapy over a one-month period, the patient's catatonia was resolved, and he was discharged on no medication with the schizophrenia in remission. The second patient was a 22-year-old woman who developed NMS after five weeks of therapy with haloperidol and thiothixene for an acute episode of abnormal behavior. She did not respond to therapy with cooling blankets, acetaminophen, antibiotics, and amobarbital sodium. Dantrolene sodium therapy produced no improvement except for some relief of muscular rigidity. Electroconvulsive therapy (22 treatments over one month) successfully decreased the patient's elevated liver enzymes and leukocyte count, but periodic temperature elevations and catatonia continued. Prompt diagnosis and treatment of NMS are essential, as the mortality rate is 20%. Acute lethal catatonia and malignant hyperthermia are considered in differential diagnosis. Both central and peripheral pathophysiologic mechanisms are probably involved in NMS, and most cases are seen in patients with psychiatric illness. Onset of NMS does not seem related to duration of neuroleptic therapy and, in susceptible persons, additional factors may be required to trigger onset of NMS. Symptoms, including diffuse muscular rigidity, akinesia, and fever, develop within 24-72 hours. Neurologic symptoms may develop or worsen, and leukocytosis and elevated levels of liver enzymes occur. Death can result from respiratory or cardiovascular failure, and rhabdomyolysis can lead to acute renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine inhibits somatolactin gene expression in tilapia pituitary cells through the dopamine D2 receptors.

PubMed

Jiang, Quan; Lian, Anji; He, Qi

2016-07-01

Dopamine (DA) is an important neurotransmitter in the central nervous system of vertebrates and possesses key hypophysiotropic functions. Early studies have shown that DA has a potent inhibitory effect on somatolactin (SL) release in fish. However, the mechanisms responsible for DA inhibition of SL gene expression are largely unknown. To this end, tilapia DA type-1 (D1) and type-2 (D2) receptor transcripts were examined in the neurointermediate lobe (NIL) of the tilapia pituitary by real-time PCR. In tilapia, DA not only was effective in inhibiting SL mRNA levels in vivo and in vitro, but also could abolish pituitary adenylate cyclase-activating polypeptide (PACAP)- and salmon gonadotropin-releasing hormone (sGnRH)-stimulated SL gene expression at the pituitary level. In parallel studies, the specific D2 receptor agonists quinpirole and bromocriptine could mimic the DA-inhibited SL gene expression. Furthermore, the D2 receptor antagonists domperidone and (-)-sulpiride could abolish the SL response to DA or the D2 agonist quinpirole, whereas D1 receptor antagonists SCH23390 and SKF83566 were not effective in this respect. In primary cultures of tilapia NIL cells, D2 agonist quinpirole-inhibited cAMP production could be blocked by co-treatment with the D2 antagonist domperidone and the ability of forskolin to increase cAMP production was also inhibited by quinpirole. Using a pharmacological approach, the AC/cAMP pathway was shown to be involved in quinpirole-inhibited SL mRNA expression. These results provide evidence that DA can directly inhibit SL gene expression at the tilapia pituitary level via D2 receptor through the AC/cAMP-dependent mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

Recent advances in the epidemiology, pathogenesis and prognosis of acute heart failure and cardiomyopathy in Africa.

PubMed

Sliwa, Karen; Mayosi, Bongani M

2013-09-01

This review addresses recent advances in the epidemiology, pathogenesis and prognosis of acute heart failure and cardiomyopathy based on research conducted in Africa. We searched Medline/PubMed for publications on acute decompensated heart failure and cardiomyopathy in Africa for the past 5 years (ie, 1 January 2008 to 31 December 2012). This was supplemented with personal communications with colleagues from Africa working in the field. A large prospective registry has shown that acute decompensated heart failure is caused by hypertension, cardiomyopathy and rheumatic heart disease in 90% of cases, a pattern that is in contrast with the dominance of coronary artery disease in North America and Europe. Furthermore, acute heart failure is a disease of the young with a mean age of 52 years, occurs equally in men and women, and is associated with high mortality at 6 months (∼18%), which is, however, similar to that observed in non-African heart failure registries, suggesting that heart failure has a dire prognosis globally, regardless of aetiology. The molecular genetics of dilated cardiomyopathy, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy in Africans is consistent with observations elsewhere in the world; the unique founder effects in the Afrikaner provide an opportunity for the study of genotype-phenotype correlations in large numbers of individuals with cardiomyopathy due to the same mutation. Advances in the understanding of the molecular mechanisms of peripartum cardiomyopathy have led to promising clinical trials of bromocriptine in the treatment of peripartum heart failure. The key challenges of management of heart failure are the urgent need to increase the use of proven treatments by physicians, and the control of hypertension in primary care and at the population level.

[Inter- and intraindividual pharmacokinetic variations in the treatment of Parkinson's disease].

PubMed

Nomoto, Masahiro; Nakatsuka, Akiko; Nagai, Masahiro; Yabe, Hayato; Moritoyo, Takashi; Moritoyo, Hiroyoko; Nisikawa, Noriko

2005-11-01

In the treatment of Parkinson's disease, levodopa, DCI, MAO-B inhibitor, COMT inhibitors, dopamine receptor agonists, amantadine, anticholinergics have been applied and new drugs are being developed. Levodopa is still the golden standard in the treatment of Parkinson's disease. The study on levodopa bioavailability showed 3-4 times differences in individual patients. Drug-food interactions are prominent in levodopa. Low protein food increased levodopa bioavailability and improved no ON or delayed ON in the treatment of Parkinson's disease. Vitamine C or magnesium did not alter the bioavailability of levodopa. The bioavailability of levodopa between the levodopa/carbidioa (100/12.5) group and the levodopa/benserazide (100/25) group was studied in patients with Parkinson's disease by population PK study. C(max) of levodopa in levodeopa/benserazide group was twice as high as in levodopa/carbidopa group. Domperidone, a dopamine receptor antagonist applied as an antiemetic inceases vowel movement. The effect of domperidone on levodopa bioavailability was studied, and the combination of domperidone with levodopa increased AUC of levodopa. Clarythromycin or grape fruit juice inhibits both of CYP3A4 and P-glycoprotein which work on metabolism and absorption of drugs. Coadministration of clarythromycin with ergot alkaloids such as cabergoline or bromocriptine increased the AUC up to 2-3 times. Amantadine is excreted through kidney without being metabolized and renal function is the most important factor in the blood concentration of amantadine. In elder women with the body weight of 50 kg or less, creatinine clearance is less than 50 ml/min even though the serum creatinine is within the normal range. Selegiline is metabolized through CYP2D6 and 3A4. Coadministration of qunidine, cimetidine, maclorides, antifungals, grape fruit juice increase the bioavailability of selegiline and may augment the antiparkinsonian effect.

Receptor-specific modulation of risk-based decision making by nucleus accumbens dopamine.

PubMed

Stopper, Colin M; Khayambashi, Shahin; Floresco, Stan B

2013-04-01

The nucleus accumbens (NAc) serves as an integral node within cortico-limbic circuitry that regulates various forms of cost-benefit decision making. The dopamine (DA) system has also been implicated in enabling organisms to overcome a variety of costs to obtain more valuable rewards. However, it remains unclear how DA activity within the NAc may regulate decision making involving reward uncertainty. This study investigated the contribution of different DA receptor subtypes in the NAc to risk-based decision making, assessed with a probabilistic discounting task. In well-trained rats, D1 receptor blockade with SCH 23,390 decreased preference for larger, uncertain rewards, which was associated with enhanced negative-feedback sensitivity (ie, an increased tendency to select a smaller/certain option after an unrewarded risky choice). Treatment with a D1 agonist (SKF 81,297) optimized decision making, increasing choice of the risky option when reward probability was high, and decreasing preference under low probability conditions. In stark contrast, neither blockade of NAc D2 receptors with eticlopride, nor stimulation of these receptors with quinpirole or bromocriptine influenced risky choice. In comparison, infusion of the D3-preferring agonist PD 128,907 decreased reward sensitivity and risky choice. Collectively, these results show that mesoaccumbens DA refines risk-reward decision biases via dissociable mechanisms recruiting D1 and D3, but not D2 receptors. D1 receptor activity mitigates the effect of reward omissions on subsequent choices to promote selection of reward options that may have greater long-term utility, whereas excessive D3 receptor activity blunts the impact that larger/uncertain rewards have in promoting riskier choices.

Emergency reconstructive endovascular management of intraoperative complications involving the internal carotid artery from trans-sphenoidal surgery.

PubMed

Griauzde, Julius; Gemmete, Joseph J; Pandey, Aditya S; McKean, Erin L; Sullivan, Stephen E; Chaudhary, Neeraj

2015-01-01

To report our experience with intraoperative complications involving the internal carotid artery (ICA) during trans-sphenoidal surgery and their outcome with reconstructive endovascular management. A retrospective review was conducted of patients with an ICA injury related to trans-sphenoidal surgery from 2000 to 2012. Demographic data, clinical charts, indications for treatment, radiographic images, lesion characteristics, operative notes, endovascular procedure notes and post-procedure hospital course were reviewed. Three men and one woman of mean age of 52 years (range 33-74) were identified. The lesions included two macroadenomas, one meningioma and one chondrosarcoma. Risk factors for ICA rupture included two patients with carotid dehiscence, one with sphenoid septal attachment to the ICA, two with revision surgery, one with prior radiation to the tumor, one with bromocriptine treatment and two with acromegaly. In three patients, covered stent placement achieved hemostasis at the site of injury within the ICA. One patient developed delayed bleeding 6 h after covered stent placement and underwent successful endovascular occlusion of the ICA but died 6 days after the injury. The fourth patient had an intraoperative ICA stroke requiring suction thrombectomy, thrombolysis, stent placement and evacuation of an epidural hematoma. At 1-year follow-up, two patients had a modified Rankin score (mRS) and National Institute of Health Stroke Scale (NIHSS) score of 0; in the patient who had a stroke the mRS score was 1 and the NIHSS score 2. Endovascular management with arterial reconstruction is helpful in the treatment of ICA injuries during trans-sphenoidal surgery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Psychotic Symptoms Associated with the use of Dopaminergic Drugs, in Patients with Cocaine Dependence or Abuse

PubMed Central

Roncero, Carlos; Abad, Alfonso C.; Padilla-Mata, Antonio; Ros-Cucurull, Elena; Barral, Carmen; Casas, Miquel; Grau-López, Lara

2017-01-01

Background In the field of dual diagnosis, physicians are frequently presented with pharmacological questions. Questions about the risk of developing psychotic symptoms in cocaine users who need treatment with dopaminergic drugs could lead to an undertreatment. Objective Review the presence of psychotic symptoms in patients with cocaine abuse/dependence, in treatment with dopaminergic drugs. Methods Systematic PubMed searches were conducted including December 2014, using the keywords: “cocaine”, dopaminergic drug (“disulfuram-methylphenidate-bupropion-bromocriptine-sibutramine-apomorphine-caffeine”) and (“psychosis-psychotic symptoms-delusional-paranoia”). Articles in English, Spanish, Portuguese, French, and Italian were included. Articles in which there was no history of cocaine abuse/dependence, absence of psychotic symptoms, systematic reviews, and animal studies, were excluded. Results 313 papers were reviewed. 7 articles fulfilled the inclusion-exclusion criteria. There is a clinical trial including 8 cocaine-dependent patients using disulfiram in which 3 of them presented psychotic symptoms and 6 case-reports: disulfuram (1), methylphenidate (1), disulfiram with methylphenidate (2), and bupropion (2), reporting psychotic symptoms, especially delusions of reference and persecutory ideation. Conclusion Few cases have been described, which suggests that the appearance of these symptoms is infrequent. The synergy of dopaminergic effects or the dopaminergic sensitization in chronic consumption are the explanatory theories proposed by the authors. In these cases, a relationship was found between taking these drugs and the appearance of psychotic symptoms. Given the low number of studies found, further research is required. The risk of psychotic symptoms seems to be acceptable if we compare it with the benefits for the patients but a closer monitoring seems to be advisable. PMID:27009114

[Drugs during preeclampsia. Fetal risks and pharmacology].

PubMed

Serreau, R

2010-04-01

During pregnancy, the maternal, placental and fetal physiological characteristics constantly evolve and thereby constantly alter drug bioavailability in the mother and feto-placental unit. Gastric emptying time is increased and bowel movements are reduced. Distribution in the maternal body is mainly influenced by body mass variations, water content and fat stores. Metabolic capacity of the liver appears unchanged but renal clearance of drugs is gradually increased. The placental transfer of most drugs mainly consists of passive diffusion between the maternal and fetal circulations, along their respective concentration gradients. Only the free, unbound and non-ionized fraction of the drug readily crosses the membranes. Four anti-hypertensive drugs have been granted a license for the treatment of PE since the year 2000: these are Clonidine (Catapressan), Nicardipine (Loxen+), Labetalol (Trandate), Dihydralazine (Nepressol). Dihydralazine, Labetalol and Nicardipine are not contraindicated in the breast feeding mother. The administration of a long acting Benzodiazepine during pregnancy can lead to new born intoxication of variable severity and duration. These symptoms may precede a withdrawal syndrome (hyper-excitability, tremor, gastro-intestinal upset, such as diarrhea or vomiting). Breast feeding by mothers using benzodiazepines (Nitrazepam and Midazolam) is not recommended. In France, the use of low molecular weight heparins is not recommended during pregnancy whereas in the United States, they are recommended as a prophylactic measure. Their high molecular weight prevents their diffusion across the placental membrane and therefore prevents any fetal or neonatal risk. Bromocriptine is used as an inhibitor of lactation. During the post-partum period, serious accidents have been described: these consist of systemic hypertension, fits, infarcts (cardiac and neurological). It is contraindicated in case of systemic hypertension. Copyright 2010 Elsevier Masson SAS. All rights reserved.

Vitex agnus-castus extracts for female reproductive disorders: a systematic review of clinical trials.

PubMed

van Die, M Diana; Burger, Henry G; Teede, Helena J; Bone, Kerry M

2013-05-01

Vitex agnus-castus L. (chaste tree; chasteberry) is a popular herbal treatment, predominantly used for a range of female reproductive conditions in Anglo-American and European practice. The objective of this systematic review was to evaluate the evidence for the efficacy and safety of Vitex extracts from randomised, controlled trials investigating women's health.Eight databases were searched using Latin and common names for Vitex and phytotherapeutic preparations of the herb as a sole agent, together with filters for randomised, controlled trials or clinical trials. Methodological quality was assessed according to the Cochrane risk of bias and Jadad scales, as well as the proposed elaboration of CONSORT for reporting trials on herbal interventions.Thirteen randomised, controlled trials were identified and twelve are included in this review, of which eight investigated premenstrual syndrome, two premenstrual dysphoric disorder, and two latent hyperprolactinaemia. For premenstrual syndrome, seven of eight trials found Vitex extracts to be superior to placebo (5 of 6 studies), pyridoxine (1), and magnesium oxide (1). In premenstrual dysphoric disorder, one study reported Vitex to be equivalent to fluoxetine, while in the other, fluoxetine outperformed Vitex. In latent hyperprolactinaemia, one trial reported it to be superior to placebo for reducing TRH-stimulated prolactin secretion, normalising a shortened luteal phase, increasing mid-luteal progesterone and 17β-oestradiol levels, while the other found Vitex comparable to bromocriptine for reducing serum prolactin levels and ameliorating cyclic mastalgia. Adverse events with Vitex were mild and generally infrequent. The methodological quality of the included studies varied, but was generally moderate-to-high. Limitations include small sample sizes in some studies, heterogeneity of conditions being treated, and a range of reference treatments.Despite some methodological limitations, the results from randomised, controlled trials to date suggest benefits for Vitex extracts in the treatment of premenstrual syndrome, premenstrual dysphoric disorder and latent hyperprolactinaemia. Further research is recommended, and greater transparency in reporting for future trials. Georg Thieme Verlag KG Stuttgart · New York.

Dopamine induces inhibitory effects on the circular muscle contractility of mouse distal colon via D1- and D2-like receptors.

PubMed

Auteri, Michelangelo; Zizzo, Maria Grazia; Amato, Antonella; Serio, Rosa

2016-08-01

Dopamine (DA) acts as gut motility modulator, via D1- and D2-like receptors, but its effective role is far from being clear. Since alterations of the dopaminergic system could lead to gastrointestinal dysfunctions, a characterization of the enteric dopaminergic system is mandatory. In this study, we investigated the role of DA and D1- and D2-like receptors in the contractility of the circular muscle of mouse distal colon by organ-bath technique. DA caused relaxation in carbachol-precontracted circular muscle strips, sensitive to domperidone, D2-like receptor antagonist, and mimicked by bromocriptine, D2-like receptor agonist. 7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH-23390), D1-like receptor antagonist, neural toxins, L-NAME (nitric oxide (NO) synthase inhibitor), 2'-deoxy-N 6 -methyl adenosine 3',5'-diphosphate diammonium salt (MRS 2179), purinergic P2Y1 antagonist, or adrenergic antagonists were ineffective. DA also reduced the amplitude of neurally evoked cholinergic contractions. The effect was mimicked by (±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrobromide (SKF-38393), D1-like receptor agonist and antagonized by SCH-23390, MRS 2179, or L-NAME. Western blotting analysis determined the expression of DA receptor proteins in mouse distal colon. Notably, SCH-23390 per se induced an increase in amplitude of spontaneous and neurally evoked cholinergic contractions, unaffected by neural blockers, L-NAME, MRS 2179, muscarinic, adrenergic, or D2-like receptor antagonists. Indeed, SCH-23390-induced effects were antagonized by an adenylyl cyclase blocker. In conclusion, DA inhibits colonic motility in mice via D2- and D1-like receptors, the latter reducing acetylcholine release from enteric neurons, involving nitrergic and purinergic systems. Whether constitutively active D1-like receptors, linked to adenylyl cyclase pathway, are involved in a tonic inhibitory control of colonic contractility is questioned.

Lack of action of prolactin suppression on the regulation of the human menstrual cycle.

PubMed

del Pozo, E; Goldstein, M; Friesen, H; Brun del Re, R; Eppenberger, U

1975-12-01

Bromocriptin (CB 154) has been found to suppress established lactation at a time when human plasma prolactin (HPRL) concentrations have already returned to the nonpregnant range. This action is due to inhibition of prolactin from the pituitary. It was then thought that a similar degree of inhibition induced during the menstrual cycle may help to uncover other possible biological actions of prolactin. In an attempt to elucidate this question eight breast-feeding mothers and seven normally menstruating volunteers underwent treatment with CB 154, including blood sampling during a sleep period. The dosage was 1 mg., three times daily, for 14 days in the first group and for a whole cycle in the normal volunteers. A control cycle preceded drug administration in the latter group. Prolactin (HPRL), growth hormone (HGH), luteotropin (LH), progesterone (PG), and estradiol (E2) were estimated (mean +/- standard error) along the menstrual cycles in the normal volunteers. HPRL and milk volumes were measured in the breast-feeding women in the base-line period and during treatment. In the postpartum group, basal HPRL had already reached normal levels prior to therapy (10.8 +/- 1.0 ng. per milliliter) and was significantly (p less than 0.002) depressed to 3.7 +/- 0.4 ng. per milliliter by CB 154. This degree of inhibition was effective in suppressing lactation within 24 to 48 hours in all of the subjects in that group. The fall in plasma HPRL from 9.5 +/- 1.5 ng. per milliliter to 3.2 +/- 0.2 ng. per milliliter observed in the normally menstruating women was similar to the one recorded in the breast-feeding group, but the sequence of hormonal changes during the menstrual cycle was not altered by treatment. The overnight study ensured around-the-clock prolactin inhibition. Results indicate no action of prolactin in the regulation of the human menstrual cycle at levels of inhibition at which a biological action of this hormone is clearly suppressed.

Prolactin-derived vasoinhibins increase anxiety- and depression-related behaviors.

PubMed

Zamorano, Miriam; Ledesma-Colunga, Maria G; Adán, Norma; Vera-Massieu, Camila; Lemini, Maria; Méndez, Isabel; Moreno-Carranza, Bibiana; Neumann, Inga D; Thebault, Stéphanie; Martínez de la Escalera, Gonzalo; Torner, Luz; Clapp, Carmen

2014-06-01

The hormone prolactin (PRL) regulates neuroendocrine and emotional stress responses. It is found in the hypothalamus, where the protein is partially cleaved to vasoinhibins, a family of N-terminal antiangiogenic PRL fragments ranging from 14 to 18kDa molecular masses, with unknown effects on the stress response. Here, we show that the intracerebroventricular administration of a recombinant vasoinhibin, containing the first 123 amino acids of human PRL that correspond to a 14kDa PRL, exerts anxiogenic and depressive-like effects detected in the elevated plus-maze, the open field, and the forced swimming tests. To investigate whether stressor exposure affects the generation of vasoinhibins in the hypothalamus, the concentrations of PRL mRNA, PRL, and vasoinhibins were evaluated in hypothalamic extracts of virgin female rats immobilized for 30min at different time points after stress onset. The hypothalamic levels of PRL mRNA and protein were higher at 60min but declined at 360min to levels seen in non-stressed animals. The elevation of hypothalamic PRL did not correlate with the stress-induced increase in circulating PRL levels, nor was it modified by blocking adenohypophyseal PRL secretion with bromocriptine. A vasoinhibin having an electrophoretic migration rate corresponding to 17kDa was detected in the hypothalamus. Despite the elevation in hypothalamic PRL, the levels of this hypothalamic vasoinhibin were similar in stressed and non-stressed rats. Stress reduced the rate of cleavage of PRL to this vasoinhibin as shown by the incubation of recombinant PRL with hypothalamic extracts from stressed rats. These results suggest that vasoinhibins are potent anxiogenic and depressive factors and that stress increases PRL levels in the hypothalamus partly by reducing its conversion to vasoinhibins. The reciprocal interplay between PRL and vasoinhibins may represent an effective mechanism to regulate anxiety and depression. Copyright © 2014 Elsevier Ltd. All rights reserved.

Obesity-resistant S5B rats showed great cocaine conditioned place preference than the obesity-prone OM rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thanos, P.K.; Wang, G.; Thanos, P.K..

Dopamine (DA) and the DA D2 receptor (D2R) are involved in the rewarding and conditioned responses to food and drug rewards. Osborne-Mendel (OM) rats are genetically prone and S5B/P rats are genetically resistant to obesity when fed a high-fat diet. We hypothesized that the differential sensitivity of these two rat strains to natural rewards may also be reflected in sensitivity to drugs of abuse. Therefore, we tested whether OM and S5B/P rats showed a differential preference to cocaine using conditioned place preference (CPP). To also evaluate whether there is specific involvement of the D2R in this differential conditioning sensitivity, wemore » then tested whether the D2R agonist bromocriptine (BC) would differentially affect the effects of cocaine in the two strains. OM and S5B/P rats were conditioned with cocaine (5 or 10 mg/kg) in one chamber and saline in another for 8 days. Rats were then tested for cocaine preference. The effects of BC (0.5, 1, 5, 10, 20 mg/kg) on cocaine preference were then assessed in subsequent test sessions. OM rats did not show a significant preference for the cocaine-paired chamber on test day. Only the S5B/P rats showed cocaine CPP. Later treatment with only the highest dose of BC resulted in reduced cocaine CPP in S5B/P rats when treated with 5 mg/kg cocaine and in OM rats treated with 10 mg/kg cocaine. Our results indicated that obesity-resistant S5B rats showed greater cocaine CPP than the obesity-prone OM rats. These findings do not support a theory of common vulnerability for reinforcer preferences (food and cocaine). However, they show that BC reduced cocaine conditioning effects supporting at least a partial regulatory role of D2R in conditioned responses to drugs.« less

Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

PubMed

Pahwa, R; Factor, S A; Lyons, K E; Ondo, W G; Gronseth, G; Bronte-Stewart, H; Hallett, M; Miyasaki, J; Stevens, J; Weiner, W J

2006-04-11

To make evidence-based treatment recommendations for the medical and surgical treatment of patients with Parkinson disease (PD) with levodopa-induced motor fluctuations and dyskinesia. To that end, five questions were addressed. 1. Which medications reduce off time? 2. What is the relative efficacy of medications in reducing off time? 3. Which medications reduce dyskinesia? 4. Does deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus interna (GPi), or ventral intermediate (VIM) nucleus of the thalamus reduce off time, dyskinesia, and antiparkinsonian medication usage and improve motor function? 5. Which factors predict improvement after DBS? A 10-member committee including movement disorder specialists and general neurologists evaluated the available evidence based on a structured literature review including MEDLINE, EMBASE, and Ovid databases from 1965 through June 2004. 1. Entacapone and rasagiline should be offered to reduce off time (Level A). Pergolide, pramipexole, ropinirole, and tolcapone should be considered to reduce off time (Level B). Apomorphine, cabergoline, and selegiline may be considered to reduce off time (Level C). 2. The available evidence does not establish superiority of one medicine over another in reducing off time (Level B). Sustained release carbidopa/levodopa and bromocriptine may be disregarded to reduce off time (Level C). 3. Amantadine may be considered to reduce dyskinesia (Level C). 4. Deep brain stimulation of the STN may be considered to improve motor function and reduce off time, dyskinesia, and medication usage (Level C). There is insufficient evidence to support or refute the efficacy of DBS of the GPi or VIM nucleus of the thalamus in reducing off time, dyskinesia, or medication usage, or to improve motor function. 5. Preoperative response to levodopa predicts better outcome after DBS of the STN (Level B).

Giant prolactinomas larger than 60 mm in size: a cohort of massive and aggressive prolactin-secreting pituitary adenomas.

PubMed

Shimon, Ilan; Sosa, Ernesto; Mendoza, Victoria; Greenman, Yona; Tirosh, Amit; Espinosa, Etual; Popovic, Vera; Glezer, Andrea; Bronstein, Marcello D; Mercado, Moises

2016-08-01

Prolactin (PRL)-secreting macroadenomas usually measure between 10 and 40 mm. Giant (adenoma size ≥40 mm) PRL-tumors are not common, and larger prolactinomas (maximal diameter ≥60 mm) are rare, and their management outcomes have not been well characterized. We have identified 18 subjects (16 men, 2 females) with giant PRL-adenomas (size ≥60 mm; PRL > 1000 ng/ml) and summarized their characteristics and response to treatment. Mean age was 36.3 ± 13.5 years (range 12-59 years). Mean adenoma size was 71.8 ± 10.2 mm (60-92 mm). Complaints at presentation included headaches in 11 patients, visual deterioration in 9, sexual dysfunction in 9 males, and behavioral changes in two. Fourteen (78 %) had visual field defects. Mean PRL at presentation was 28,465 ng/ml (range 1300-270,000). All patients were treated with cabergoline (3.9 ± 2.0 mg/week), except for one who received bromocriptine. Treatment achieved PRL normalization in 11/18 patients within a median interval of 20 months. Visual improvement occurred in 12/14 patients with pre-treatment visual abnormalities. Nine patients underwent surgery (transsphenoidal, 7; transcranial, 2). None of the seven patients with elevated PRL before surgery achieved remission post-operatively. After a follow-up of 7.8 ± 5.1 years, 15/18 patients had significant adenoma shrinkage. Eleven patients are normoprolactinemic, 3 are partially controlled (PRL < 3 × ULN), and 4 remain with significantly elevated PRL. Most patients reported disappearance or improvement of their complaints. These enormous PRL-adenomas are invasive but respond fairly well to medical treatment. Long-term therapy with high dose cabergoline together with a pituitary surgery in some patients was the key for their successful management, achieving biochemical and clinical remission in most patients.

Casticin, a flavonoid isolated from Vitex rotundifolia, inhibits prolactin release in vivo and in vitro

PubMed Central

Ye, Qi; Zhang, Qiao-yan; Zheng, Cheng-jian; Wang, Yang; Qin, Lu-ping

2010-01-01

Aim: To investigate the anti-hyperprolactinemia activity of casticin, a flavonoid isolated from Vitex rotundifolia, and elucidate its molecular mechanism. Methods: Hyperprolactinemia (MIHP) was induced by administration of metoclopramide dihydrochloride (50 mg/kg, tid, ip, for 10 d) in SD rats and the primary pituitary cells were prepared from the pituitary glands of the SD rats. Prolactin concentrations were measured using a radioimmunoassay. Cell viability was measured using an MTT assay. The mRNA expression of estrogen receptor alpha and beta in rat pituitary cells was measured using semi-quantitative RT-PCR analysis. Results: The level of serum prolactin in the MIHP model group was 2.1 fold higher than that in the untreated control group (P<0.01). Casticin (10, 20, and 40 mg/kg, ip, for 7 d) reduced serum prolactin levels by 33.9%, 54.3%, and 64.7%, respectively (P<0.01). The positive control drug bromocriptine 1 mg/kg decreased the serum prolactin concentration in MIHP rats by 44.9%. 17β-Estradiol (E2) significantly increased the proliferation of pituitary cells and casticin (1 and 10 μmol/L) markedly inhibited E2-induced pituitary cell proliferation by 27.7% and 42.1%, respectively. Stimulation of pituitary cells with E2 increased prolactin secretion into the cell culture supernatants, and casticin (0.1, 1, and 10 μmol/L) significantly inhibited the prolactin release stimulated by E2 in a concentration-dependent manner. Casticin (1 and 10 μmol/L) significantly inhibited ERα mRNA expression in pituitary cells stimulated with E2 (P<0.01) but increased ERβ mRNA expression at a concentration of 10 μmol/L (P<0.01). However, casticin had no effects on proliferation and prolectin release of the unstimulated primary pituitary cells in vitro. Conclusion: Casticin inhibited the release of prolactin from pituitary cells of SD rats stimulated with E2 in vivo and in vitro. These effects might be related with inhibiting the ERα mRNA expression and increasing the ERβ mRNA expression. PMID:21042288

Mechanism of interactions of α-naphthoflavone with cytochrome P450 3A4 explored with an engineered enzyme bearing a fluorescent probe†

PubMed Central

Tsalkova, Tamara N.; Davydova, Nadezhda Y.; Halpert, James R.; Davydov, Dmitri R.

2008-01-01

Design of a partially cysteine-depleted C98S/C239S/C377S/C468A cytochrome P450 3A4 mutant designated CYP3A4(C58,C64) allowed site-directed incorporation of thiol-reactive fluorescent probes into α-helix A‥ The site of modification was identified as Cys-64 with the help of CYP3A4(C58) and CYP3A4(C64), each bearing only one accessible cysteine. Changes in the fluorescence of CYP3A4(C58,C64) labeled with 6-bromoacetyl-2-dimethylaminonaphthalene (BADAN), 7-diethylamino-3-(4’-maleimidylphenyl)-4-methylcoumarin (CPM), or monobromobimane (mBBr) were used to study the interactions with bromocriptine (BCT), 1-pyrenebutanol (1-PB), testosterone (TST), and α-naphthoflavone (ANF). Of these substrates only ANF has a specific effect, causing a considerable decrease in fluorescence intensity of BADAN and CPM and increasing the fluorescence of mBBr. This ANF-binding event in the case of BADAN-modified enzyme is characterized by an S50 of 18.2 ± 0.7, compared with the value of 2.2 ± 0.3 for the ANF-induced spin transition, thus revealing an additional low affinity binding site. Studies of the effect of TST, 1-PB, and BCT on the interactions of ANF monitored by changes in fluorescence of CYP3A4(C58,C64)-BADAN or by the ANF-induced spin transition revealed no competition by these substrates. Investigation of the kinetics of fluorescence increase upon H2O2-dependent heme depletion suggests that labeled CYP3A4(C58,C64) is represented by two conformers, one of which has the fluorescence of the BADAN and CPM labels completely quenched, presumably by photoinduced electron transfer from the neighboring Trp-72 and/or Tyr-68 residues. The binding of ANF to the newly discovered binding site appears to affect the interactions of the label with the above residue(s), thus modulating the fraction of the fluorescent conformer. PMID:17198380

Clinical characteristics of patients from the worldwide registry on peripartum cardiomyopathy (PPCM): EURObservational Research Programme in conjunction with the Heart Failure Association of the European Society of Cardiology Study Group on PPCM.

PubMed

Sliwa, Karen; Mebazaa, Alexandre; Hilfiker-Kleiner, Denise; Petrie, Mark C; Maggioni, Aldo P; Laroche, Cecile; Regitz-Zagrosek, Vera; Schaufelberger, Maria; Tavazzi, Luigi; van der Meer, Peter; Roos-Hesselink, Jolien W; Seferovic, Petar; van Spandonck-Zwarts, Karin; Mbakwem, Amam; Böhm, Michael; Mouquet, Frederic; Pieske, Burkert; Hall, Roger; Ponikowski, Piotre; Bauersachs, Johann

2017-09-01

The purpose of this study is to describe disease presentation, co-morbidities, diagnosis and initial therapeutic management of patients with peripartum cardiomyopathy (PPCM) living in countries belonging to the European Society of Cardiology (ESC) vs. non-ESC countries. Out of 500 patients with PPCM entered by 31 March 2016, we report on data of the first 411 patients with completed case record forms (from 43 countries) entered into this ongoing registry. There were marked differences in socio-demographic parameters such as Human Development Index, GINI index on inequality, and Health Expenditure in PPCM patients from ESC vs. non-ESC countries (P < 0.001 each). Ethnicity was Caucasian (34%), Black African (25.8%), Asian (21.8%), and Middle Eastern backgrounds (16.4%). Despite the huge disparities in socio-demographic factors and ethnic backgrounds, baseline characteristics are remarkably similar. Drug therapy initiated post-partum included ACE inhibitors/ARBs and mineralocorticoid receptor antagonists with identical frequencies in ESC vs. non-ESC countries. However, in non-ESC countries, there was significantly less use of beta-blockers (70.3% vs. 91.9%) and ivabradine (1.4% vs. 17.1%), but more use of diuretics (91.3% vs. 68.8%), digoxin (37.0% vs. 18.0%), and bromocriptine (32.6% vs. 7.1%) (P < 0.001). More patients in non-ESC vs. ESC countries continued to have symptomatic heart failure after 1 month (92.3% vs. 81.3%, P < 0.001). Venous thrombo-embolic events, arterial embolizations, and cerebrovascular accidents were documented in 28 of 411 patients (6.8%). Neonatal death rate was 3.1%. PPCM occurs in women from different ethnic backgrounds globally. Despite marked differences in socio-economic background, mode of presentation was largely similar. Embolic events and persistent heart failure were common within 1 month post-diagnosis and required intensive, multidisciplinary management. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Cholinergic, But Not Dopaminergic or Noradrenergic, Enhancement Sharpens Visual Spatial Perception in Humans

PubMed Central

Wallace, Deanna L.

2017-01-01

The neuromodulator acetylcholine modulates spatial integration in visual cortex by altering the balance of inputs that generate neuronal receptive fields. These cholinergic effects may provide a neurobiological mechanism underlying the modulation of visual representations by visual spatial attention. However, the consequences of cholinergic enhancement on visuospatial perception in humans are unknown. We conducted two experiments to test whether enhancing cholinergic signaling selectively alters perceptual measures of visuospatial interactions in human subjects. In Experiment 1, a double-blind placebo-controlled pharmacology study, we measured how flanking distractors influenced detection of a small contrast decrement of a peripheral target, as a function of target-flanker distance. We found that cholinergic enhancement with the cholinesterase inhibitor donepezil improved target detection, and modeling suggested that this was mainly due to a narrowing of the extent of facilitatory perceptual spatial interactions. In Experiment 2, we tested whether these effects were selective to the cholinergic system or would also be observed following enhancements of related neuromodulators dopamine or norepinephrine. Unlike cholinergic enhancement, dopamine (bromocriptine) and norepinephrine (guanfacine) manipulations did not improve performance or systematically alter the spatial profile of perceptual interactions between targets and distractors. These findings reveal mechanisms by which cholinergic signaling influences visual spatial interactions in perception and improves processing of a visual target among distractors, effects that are notably similar to those of spatial selective attention. SIGNIFICANCE STATEMENT Acetylcholine influences how visual cortical neurons integrate signals across space, perhaps providing a neurobiological mechanism for the effects of visual selective attention. However, the influence of cholinergic enhancement on visuospatial perception remains unknown. Here we demonstrate that cholinergic enhancement improves detection of a target flanked by distractors, consistent with sharpened visuospatial perceptual representations. Furthermore, whereas most pharmacological studies focus on a single neurotransmitter, many neuromodulators can have related effects on cognition and perception. Thus, we also demonstrate that enhancing noradrenergic and dopaminergic systems does not systematically improve visuospatial perception or alter its tuning. Our results link visuospatial tuning effects of acetylcholine at the neuronal and perceptual levels and provide insights into the connection between cholinergic signaling and visual attention. PMID:28336568

Patterns of pharmacologic treatment in US patients with acromegaly.

PubMed

Broder, Michael S; Chang, Eunice; Ludlam, William H; Neary, Maureen P; Carmichael, John D

2016-05-01

To establish a baseline pattern of care across academic and community settings, it is important to examine the contemporary treatment of acromegaly. We characterized medical treatment patterns for acromegaly in the US to develop a basis for tracking concordance with guidelines. Acromegaly patients were identified in two commercial claims databases for this retrospective analysis. Study subjects had ≥2 medical claims with acromegaly (ICD-9-CM code 253.0) and ≥1 claim for pharmacotherapy (bromocriptine, cabergoline, octreotide SA, octreotide LAR, lanreotide, or pegvisomant) in the study timeframe (1 January 2002-31 December 2013). Patients were considered newly treated if they were continuously enrolled for ≥6 months before first observed treatment and had no claim for pharmacologic treatment during that time. Outcomes included various pharmacotherapies, including combination treatments, and differences between lines of therapy. A total of 3150 patients had ≥1 pharmacotherapy (mean age: 46.5 years; 50.1% were female); 1471 were newly treated. Somatostatin receptor ligands (SRLs) were the most common drug class used first line (57.2%); cabergoline (27.8%) was the most common treatment, followed by octreotide LAR (22.3%) and lanreotide (19.7%). SRLs were also the most commonly used second-line (42.8%) and third-line pharmacotherapies (43.9%), with combination therapy (23.2%) and octreotide LAR (19.8%) as the most commonly used treatments, respectively. This study, representing the largest claims-based analysis of acromegaly to date, used two databases across a 12 year period to examine complex treatment patterns in a difficult-to-study disease. Although wide variation in acromegaly treatment patterns exists in US clinical practice, in first-line, second-line, and third-line therapy, SRL was the most commonly used drug class. Drug combinations also varied considerably across lines of therapy. The switching between different monotherapies and varied use of drugs in combination may suggest an unmet need for alternative treatment options. Our claims-based technique of examining treatment patterns may be used for other rare diseases, although high censoring rates may be a challenge.

An interaction between levodopa and enteral nutrition resulting in neuroleptic malignant-like syndrome and prolonged ICU stay.

PubMed

Bonnici, André; Ruiner, Carola-Ellen; St-Laurent, Lyne; Hornstein, David

2010-09-01

To describe a probable interaction between enteral feeds and levodopa leading to neuroleptic malignant-like syndrome (NMLS) in a polytrauma patient with Parkinson's disease (PD). A 63-year-old morbidly obese male polytrauma patient with PD and type 2 diabetes mellitus was admitted to our intensive care unit postoperatively. Enteral feeds were administered per nasogastric tube and provided 0.88 g /kg/day of protein based on ideal body weight (IBW). His PD medications (pramipexole, entacapone, and immediate-release levodopa/carbidopa 100 mg/25 mg, 1.5 tablets 4 times daily) were administered via nasogastric tube. To achieve better glycemic control, his enteral feeds were changed to a formula that provided 1.8 g/kg/day of protein based on IBW. In the following 24 hours, the patient's mental status deteriorated and he was reintubated. He developed a high fever (40.5 degrees C), leukocytosis, elevated serum creatine kinase (CK) (480-1801 units/L), and acute renal impairment. His enteral nutrition was changed to decrease protein intake to 1.0 g/kg/day based on IBW and he was given bromocriptine 5 mg 3 times daily via nasogastric tube. Within 24 hours, the patient's mental status improved, his temperature and CK decreased, and his renal function began to improve; the values returned to baseline levels on the 18th day of admission. Withdrawal or dose reduction of levodopa in patients with PD has been reported to precipitate NMLS, which is potentially fatal. Because dietary protein can decrease the absorp0tion of levodopa, a potential for an interaction between levodopa and enteral feedings exists, although published reports of such an interaction are limited. In this patient, the likelihood that a drug-nutrient interaction occurred between levodopa and enteral feedings is considered to be probable based on the Naranjo probability scale and the Horn Drug Interaction Probability Scale. Health-care professionals should be aware of the interaction between levodopa and protein content of enteral nutrition to avoid the occurrence of NMLS in patients with PD.

Dopamine-regulated adrenocorticotropic hormone secretion in lactating rats: functional plasticity of melanotropes.

PubMed

Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E; Nagy, Gyorgy M; Vecsernyés, Miklós

2009-01-01

Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and beta-lipotropin in corticotropes of the anterior lobe, and to alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D(2) type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence alpha-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E(2))-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in alpha-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by alpha-methyl-p-tyrosine (alphaMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma alpha-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E(2) animals. In lactating mothers, BRC was able to block ACTH responses induced by both alphaMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is regulated by NEDA neurons. Copyright 2009 S. Karger AG, Basel.

Dopamine-Regulated Adrenocorticotropic Hormone Secretion in Lactating Rats: Functional Plasticity of Melanotropes

PubMed Central

Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E.; Nagy, György M.; Vecsernyés, Miklós

2009-01-01

Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and β-lipotropin in corticotropes of the anterior lobe, and to α-melanocyte-stimulating hormone (α-MSH) and β-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D2 type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence α-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E2)-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in α-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by α-methyl-p-tyrosine (αMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma α-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E2 animals. In lactating mothers, BRC was able to block ACTH responses induced by both αMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is regulated by NEDA neurons. PMID:19641299

Gastric mucosal lesions induced by complete dopamine system failure in rats. The effects of dopamine agents, ranitidine, atropine, omeprazole and pentadecapeptide BPC 157.

PubMed

Sikiric, P; Separovic, J; Buljat, G; Anic, T; Stancic-Rokotov, D; Mikus, D; Duplancic, B; Marovic, A; Zoricic, I; Prkacin, I; Lovric-Bencic, M; Aralica, G; Ziger, T; Perovic, D; Jelovac, N; Dodig, G; Rotkvic, I; Mise, S; Seiwerth, S; Turkovic, B; Grabarevic, Z; Petek, M; Rucman, R

2000-01-01

Up to now, for gastric lesions potentiation or induction, as well as determination of endogenous dopamine significance, dopamine antagonist or dopamine vesicle depletor were given separately. Therefore, without combination studies, the evidence for dopamine significance remains split on either blockade of dopamine post-synaptic receptor or inhibition of dopamine storage, essentially contrasting with endogenous circumstances, where both functions could be simultaneously disturbed. For this purpose, a co-administration of reserpine and haloperidol, a dopamine granule depletor combined with a dopamine antagonist with pronounced ulcerogenic effect, was tested, and the rats were sacrificed 24 h after injurious agent(s) administration. Haloperidol (5 mg x kg(-1) b.w. i.p.), given alone, produced the lesions in all rats. Reserpine (5 mg x kg(-1) b.w. i.p.), given separately, also produced lesions. When these agents were given together, the lesions were apparently larger than in the groups injured with separate administration of either haloperidol or reserpine alone. Along with our previous results, when beneficial agents were co-administered, all dopaminomimetics (bromocriptine 10 mg, apomophine 1 mg, amphetamine 20 mg x kg(-1) i.p.) apparently attenuated the otherwise consistent haloperidol-gastric lesions. Likewise, an apparent inhibition of the reserpine-lesions was noted as well. However, if they were given in rats injured with combination of haloperidol and reserpine, their otherwise prominent beneficial effects were absent. Ranitidine (10 mg), omeprazole (10 mg), atropine (10 mg), pentadecapeptide BPC 157 (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) (10 microg or 10 ng x kg(-1) i.p.) evidently prevented both haloperidol-gastric lesions and reserpine-gastric lesions. Confronted with potentiated lesions following a combination of haloperidol and reserpine, these agents maintained their beneficial effects, noted in the rats treated with either haloperidol or reserpine alone. The failure of dopaminomimetics could be most likely due to more extensive inhibition of endogenous dopamine system activity, and need for remained endogenous dopamine for their salutary effect, whereas the beneficial activities of ranitidine, omeprazole, atropine, pentadecapeptide BPC 157 following dopamine system inhibition by haloperidol+reserpine suggest their corresponding systems parallel those of dopamine system, and they may function despite extensive inhibition of endogenous dopamine system activity.

Endocrine aspects of paediatric rheumatic diseases.

PubMed

Neeck, G; Michels, H

1996-05-01

Compared to the now numerous studies on the endocrinology of rheumatic diseases in adults, only a small number of studies has been published on children with rheumatic diseases. Prolactin has been most extensively investigated, showing interesting parallels with the findings in adults with rheumatological diseases. Thus, analogous to adult RA most forms of JRA or JCA (with the exception of ANA-positive JRA with uveitis) appear to show, if anything, low to normal levels of prolactin. Since the prolactin levels in adult RA depend on the inflammatory activity, and the physiological prolactin secretion decreases in chronic stress (especially sleep disorders), these results are most likely to be explained as reactive non-specific mechanisms in the stress of the disease. However, specific mechanisms are also being discussed to explain the low prolactin levels in adult RA. The results of prolactin measurements in juvenile SLE, juvenile ankylosing spondylitis and ANA-positive JRA with a raised incidence of uveitis, contrast with this. These conditions sometimes show significantly higher prolactin levels compared to healthy controls. A correlation of the increase of prolactin concentration with the inflammatory activity has been described for juvenile ankylosing spondylitis. These results correlate well with those of adult forms such as diseases of the seronegative spondyloarthropathies type, SLE and iridocyclitis. Raised prolactin concentrations are also found in these diseases. The inflammation promoting and immunostimulatory effects of prolactin found especially in animal experiments are confirmed clinically in these diseases by reports of successful treatments with the prolactin inhibitor, bromocriptine. The results available up to now for human growth hormone in JRA and JCA tend to be comparable with the results for prolactin in these form of paediatric rheumatological diseases. Besides normal values above, all lowered concentrations are measured for this hormone. Apart from other non-specific factors, its diminished secretion is mainly determined by the inflammatory activity of the disease. Low levels of growth hormone are likely to be a significant factor in the growth retardation in children with inflammatory rheumatological diseases. Up to now, the small number of investigations on gonadotrophins and the sex hormones in juvenile SLE and various forms of JRA published have not as yet yielded unequivocal results. The endocrine aspects of paediatric rheumatological diseases are thus still incompletely elucidated. However, there are many promising avenues for further fruitful research in this field.

Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole, sulphasalazine and methylprednisolone.

PubMed

Sikiric, P; Seiwerth, S; Grabarevic, Z; Balen, I; Aralica, G; Gjurasin, M; Komericki, L; Perovic, D; Ziger, T; Anic, T; Prkacin, I; Separovic, J; Stancic-Rokotov, D; Lovric-Bencic, M; Mikus, D; Staresinic, M; Aralica, J; DiBiaggio, N; Simec, Z; Turkovic, B; Rotkvic, I; Mise, S; Rucman, R; Petek, M; Sebecic, B; Ivasovic, Z; Boban-Blagaic, A; Sjekavica, I

2001-01-01

Recently, we showed cysteamine-duodenal lesions without gastric acid, since they were induced also in gastrectomized rats, as in naive rats, and they were inhibited by the novel stomach pentadecapeptide BPC 157 as well as standard antiulcer drugs (i.e. cimetidine, ranitidine, omeprazole, bromocriptine, atropine). Therefore, as an advantage of considering cysteamine as a directly acting cytotoxic agent and mentioned agents as direct cytoprotective agents, the present focus was on the ulcerogenic effect of cysteamine and protective effect of gastroduodenal antiulcer agents outside upper gastrointestinal tract (i.e. in colon). Intrarectal administration of the cysteamine (200 or 400 mg/kg b.w) produced severe colon lesions (i.e. transmural inflammation with serosal involvement) in rats (30 min-72 h-experimental period), apparently distinctive from smaller lesions after non-specific irritant enema [diluted HCl solution, pH 3.8 (adjusted to pH of cysteamine solution (pH 3.8)]. All of the tested antiulcer agents were applied simultaneously with cysteamine enema (8 cm from the anus, in a volume of the 1.0 ml/rat) intraperitoneally (i.p.), intragastrically (i.g.) or intrarectally (i.r.). Pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w.), given in either regimen, previously shown to have, besides others, a particular beneficial activity just in the intestinal mucosa, inhibited these cysteamine colon lesions (assessed after 30 min, 60 min, 180 min, 24 h, 48 h, 72 h following cysteamine in a dose of either 200 or 400 mg/kg i.r.). Cysteamine-colon lesions were also attenuated by standard antiulcer agents (mg/kg b.w.), given i.p., i.g., or i.r., such as ranitidine (10), cimetidine (50), omeprazole (10), atropine (10), together with methylprednisolone (1), and sulphasalazine (50, i.r.), assessed 30 min following application of 200 mg of cysteamine. Finally, standard cysteamine duodenal lesions (assessed 24 h after a subcutaneous application of 400 mg/kg of cysteamine) were also attenuated by these agents application (given in the same doses, i.p., 1 h before cysteamine), with only exception to sulphasalazine. Thus, the extended cysteamine specific ulcerogenic effect, cysteamine colon/duodenum lesion-link and an extenuation of agents protection from upper to lower part of gastrointestinal tract (i.e. stomach pentadecapeptide BPC 157, standard antiulcer agents, cimetidine, ranitidine, atropine, omeprazole) and vice versa (remedies for inflammatory bowel disease) evidenced in the present study may be potentially important for both further experimental and clinical research.

Antipsychotics differ in their ability to internalise human dopamine D2S and human serotonin 5-HT1A receptors in HEK293 cells.

PubMed

Heusler, Peter; Newman-Tancredi, Adrian; Loock, Timothé; Cussac, Didier

2008-02-26

Antipsychotic drugs act preferentially via dopamine D(2) receptor blockade, but interaction with serotonin 5-HT(1A) receptors has attracted interest as additional target for antipsychotic treatment. As receptor internalisation is considered crucial for drug action, we tested the propensity of antipsychotics to internalise human (h)D(2S) receptors and h5-HT(1A) receptors. Agonist-induced internalisation of hemaglutinin (HA)-tagged hD(2S) and HA-h5-HT(1A) receptors expressed in HEK293 cells was increased by coexpression of G-protein coupled receptor kinase 2 and beta-arrestin2. At the HA-hD(2S) receptor, dopamine, quinpirole and bromocriptine behaved as full agonists, while S(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine [(-)-3PPP] and sarizotan were partial agonists. The typical antipsychotic, haloperidol, and the atypical compounds, olanzapine, nemonapride, ziprasidone and clozapine did not internalise HA-hD(2S) receptors, whereas aripiprazole potently internalised these receptors (>50% relative efficacy). Among antipsychotics with combined D(2)/5-HT(1A) properties, bifeprunox and (3-exo)-8-benzoyl-N-[[(2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl]methyl]-8-azabicyclo-[3.2.1]octane-3-methanamine (SSR181507) partially internalised HA-hD(2S) receptors, piperazine, 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[[5-(4-fluorophenyl)-3-pyridinyl]methyl (SLV313) and N-[(2,2-dimethyl-2,3-dihydro-benzofuran-7-yloxy)ethyl]-3-(cyclopent-1-enyl)-benzylamine (F15063) were inactive. At the HA-h5-HT(1A) receptor, serotonin, (+)-8-hydroxy-2-(di-n-propylamino)tetralin [(+)-8-OH-DPAT] and sarizotan were full agonists, buspirone acted as partial agonist. (-)-Pindolol showed little activity and no internalising properties were manifested for the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY100635). Most antipsychotics induced HA-h5-HT(1A) receptor internalisation, with an efficacy rank order: nemonapride>F15063>SSR181507>bifeprunox approximately SLV313 approximately ziprasidone>aripiprazole and potencies: SLV313>SSR181507 approximately F15063>bifeprunox approximately nemonapride approximately aripiprazole>ziprasidone. Interestingly, the internalisation induced by clozapine was only minimal, whereas aripirazole and bifeprunox were more potent for internalisation than for G-protein activation. These different profiles of antipsychotics for receptor internalisation may help to evaluate their potential therapeutic impact in the treatment of schizophrenia.

[Primary glucocorticoid resistance syndrome presenting as pseudo-precocious puberty and galactorrhea].

PubMed

Xiang, Shu-lin; He, Li-ping; Ran, Xing-wu; Tian, Hao-ming; Li, Xiu-jun; Liang, Jin-zhong

2008-09-01

Primary glucocorticoid resistance syndrome (PGRS) is a rare condition characterized by hypercortisolism without Cushing's syndrome. This report describes a 7-year-old boy of PGRS with pseudo-precocious puberty and galactorrhea as the main manifestation. His height was 135 cm and body weight was 31 kg. Pigmentation could be seen in the skin, mammary areola and penis. He had hirsutism, low hair line, coarse voice, Tanner stage 3 pubic hair, penis in adult form, accelerated linear growth, and advanced bone age (13 yr.), but normal (for age) testes. Furthermore, he had mammoplasia and galactorrhea. There were no features of glucocorticoid (GC) excess. Hepatic function was impaired (ALT 1426 IU/L, AST 611 IU/L) with no definite causes. Serum cortisol concentration was 1294 nmol/L, 777 nmol/L, 199.3 nmol/L at 8:00, 16:00 and 24:00 respectively. Plasma adrenocorticotropic hormone (ACTH) was normal or a little higher (43.9-80 ng/L). Urinary-free cortisol (UFC) was normal (55.5-62.4 microg/24 h). Serum estradiol (E2), progesterone (P), testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were normal. Serum dehydroepiandrosterone sulfate (DHEAS, 60 microg/dL) and serum prolactin (PRL, 58.7-183.9 ng/mL) level were high, urinary dehydroepiandrosterone (DHEA) level was also elevated (0.96-3.2 mg/mL). Gonadotrophin hormone-releasing hormone (GnRH) stimulation test was negative. Serum cortisol responded normally to insulin-induced hypoglycemia. However, serum cortisol and plasma ACTH concentration was suppressed to more than 50% by 0.5 mg dexamethasone (DEX). The diagnosis of PGRS was made. TREATMENT AND FOLLOW-UP: The patient received a treatment of 0.75-1.0 mg/d DEX. Because of galactorrhea, bromocriptine was given by 1.25-3.75 mg/d. After 24 months follow-up, the pigmentation was relieved and galactorrhea disappeared. No advanced development of the external genitalia and breast was found. The acceleration of the bone age was also slowed down. But he still had obvious hirsutism. No side effect of DEX was found. PGRS may present with pseudo-precocious puberty and galactorrhea. The aim of treatment in glucocorticoid resistance is to suppress the excessive secretion of ACTH and the increased production of adrenal androgens. The administration of synthetic GC with minimal intrinsic mineralocorticoid activity, such as DEX, provides a rational treatment for PGRS. Long-term DEX treatment should be individualized and carefully titrated based on the clinical manifestations and biochemical profile in order to control the clinical manifestations of the disease.

Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings.

PubMed

Arentz, Susan; Abbott, Jason Anthony; Smith, Caroline Anne; Bensoussan, Alan

2014-12-18

Polycystic ovary syndrome (PCOS) is a prevalent, complex endocrine disorder characterised by polycystic ovaries, chronic anovulation and hyperandrogenism leading to symptoms of irregular menstrual cycles, hirsutism, acne and infertility. Evidence based medical management emphasises a multidisciplinary approach for PCOS, as conventional pharmaceutical treatment addresses single symptoms, may be contra-indicated, is often associated with side effects and not effective in some cases. In addition women with PCOS have expressed a strong desire for alternative treatments. This review examines the reproductive endocrine effects in PCOS for an alternative treatment, herbal medicine. The aim of this review was to identify consistent evidence from both pre-clinical and clinical research, to add to the evidence base for herbal medicine in PCOS (and associated oligo/amenorrhoea and hyperandrogenism) and to inform herbal selection in the provision clinical care for these common conditions. We undertook two searches of the scientific literature. The first search sought pre-clinical studies which explained the reproductive endocrine effects of whole herbal extracts in oligo/amenorrhoea, hyperandrogenism and PCOS. Herbal medicines from the first search informed key words for the second search. The second search sought clinical studies, which corroborated laboratory findings. Subjects included women with PCOS, menstrual irregularities and hyperandrogenism. A total of 33 studies were included in this review. Eighteen pre-clinical studies reported mechanisms of effect and fifteen clinical studies corroborated pre-clinical findings, including eight randomised controlled trials, and 762 women with menstrual irregularities, hyperandrogenism and/or PCOS. Interventions included herbal extracts of Vitex agnus-castus, Cimicifuga racemosa, Tribulus terrestris, Glycyrrhiza spp., Paeonia lactiflora and Cinnamomum cassia. Endocrine outcomes included reduced luteinising hormone (LH), prolactin, fasting insulin and testosterone. There was evidence for the regulation of ovulation, improved metabolic hormone profile and improved fertility outcomes in PCOS. There was evidence for an equivalent effect of two herbal medicines and the pharmaceutical agents bromocriptine (and Vitex agnus-castus) and clomiphene citrate (and Cimicifuga racemosa). There was less robust evidence for the complementary combination of spirinolactone and Glycyrrhiza spp. for hyperandrogenism. Preclinical and clinical studies provide evidence that six herbal medicines may have beneficial effects for women with oligo/amenorrhea, hyperandrogenism and PCOS. However the quantity of pre-clinical data was limited, and the quality of clinical evidence was variable. Further pre-clinical studies are needed to explain the effects of herbal medicines not included in this review with current clinical evidence but an absence of pre-clinical data.

Statistical investigation of simulated fed intestinal media composition on the equilibrium solubility of oral drugs.

PubMed

Zhou, Zhou; Dunn, Claire; Khadra, Ibrahim; Wilson, Clive G; Halbert, Gavin W

2017-03-01

Gastrointestinal fluid is a complex milieu and it is recognised that gut drug solubility is different to that observed in simple aqueous buffers. Simulated gastrointestinal media have been developed covering fasted and fed states to facilitate in vitro prediction of gut solubility and product dissolution. However, the combination of bile salts, phospholipids, fatty acids and proteins in an aqueous buffered system creates multiple phases and drug solubility is therefore a complex interaction between these components, which may create unique environments for each API. The impact on solubility can be assessed through a statistical design of experiment (DoE) approach, to determine the influence and relationships between factors. In this paper DoE has been applied to fed simulated gastrointestinal media consisting of eight components (pH, bile salt, lecithin, sodium oleate, monoglyceride, buffer, salt and pancreatin) using a two level D-optimal design with forty-four duplicate measurements and four centre points. The equilibrium solubility of a range of poorly soluble acidic (indomethacin, ibuprofen, phenytoin, valsartan, zafirlukast), basic (aprepitant, carvedilol, tadalafil, bromocriptine) and neutral (fenofibrate, felodipine, probucol, itraconazole) drugs was investigated. Results indicate that the DoE provides equilibrium solubility values that are comparable to literature results for other simulated fed gastrointestinal media systems or human intestinal fluid samples. For acidic drugs the influence of pH predominates but other significant factors related to oleate and bile salt or interactions between them are present. For basic drugs pH, oleate and bile salt have equal significance along with interactions between pH and oleate and lecithin and oleate. Neutral drugs show diverse effects of the media components particularly with regard to oleate, bile salt, pH and lecithin but the presence of monoglyceride, pancreatin and buffer have significant but smaller effects on solubility. There are fourteen significant interactions between factors mainly related to the surfactant components and pH, indicating that the solubility of neutral drugs in fed simulated media is complex. The results also indicate that the equilibrium solubility of each drug can exhibit individualistic behaviour associated with the drug's chemical structure, physicochemical properties and interaction with media components. The utility of DoE for fed simulated media has been demonstrated providing equilibrium solubility values comparable with similar in vitro systems whilst also providing greater information on the influence of media factors and their interactions. The determination of a drug's gastrointestinal solubility envelope provides useful limits that can potentially be applied to in silico modelling and in vivo experiments. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Medical management of levodopa-associated motor complications in patients with Parkinson's disease.

PubMed

Jankovic, Joseph; Stacy, Mark

2007-01-01

Parkinson's disease is a neurodegenerative disorder that affects approximately 1% of people over the age of 60 years. Levodopa is standard, and often initial, therapy for patients with this condition; however, with continued treatment and as the disease progresses, up to 80% of patients experience 'wearing-off' symptoms, dyskinesias and other motor complications. These levodopa-associated problems may become disabling and profoundly affect quality of life. Medications commonly used to manage these symptoms include monoamine oxidase type B (MAO-B) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, the NMDA receptor antagonist amantadine and dopamine receptor agonists. Agents that block MAO-B, such as rasagiline and selegiline, are used as both initial and adjunctive therapy in patients with Parkinson's disease. These medications increase concentrations of dopamine in the brain by blocking its reuptake from the synaptic cleft, a mechanism that can slow motor decline, increase 'on' time and improve symptoms of Parkinson's disease. Adverse events with these agents can include confusion, hallucination and orthostatic hypotension. MAO-B inhibition may elicit drug-drug interactions if administered with TCAs, SSRIs or SNRIs. Conventional oral selegiline is associated with potentially harmful plasma concentrations of three major amphetamine metabolites, although metabolite concentrations are significantly lower with a new orally disintegrating tablet (ODT) selegiline formulation. Selegiline ODT is also absorbed more efficiently and shows less pharmacokinetic variability than conventional oral selegiline.COMT mediates peripheral catabolism of levodopa. Therefore, agents that block COMT, such as tolcapone and entacapone, increase the elimination half-life of levodopa. Given adjunctively with levodopa, COMT inhibitors can decrease 'off' time and increase 'on' time, as well as lower the daily levodopa dose. Although more potent than entacapone, tolcapone requires monitoring for hepatotoxicity. Amantadine is a noncompetitive NMDA receptor antagonist shown to lower dyskinesia scores and improve motor complications in patients with Parkinson's disease when given adjunctively with levodopa. Dopamine agonists, also used as initial and adjunctive therapy in Parkinson's disease, improve motor response and decrease 'off' time purportedly through direct stimulation of dopamine receptors. Current dopamine agonists include bromocriptine, pergolide, cabergoline, lisuride, apomorphine, pramipexole, ropinirole and rotigotine. Although effective, this class of medications can be associated with cardiovascular and psychiatric adverse effects that can limit their utility. All medications used to manage levodopa-associated motor complications in patients with Parkinson's disease have had differing degrees of success. Although head-to-head comparisons of drugs within classes are rare, some differences have emerged related to effects on motor fluctuations, dyskinesias and on/off times, as well as to adverse effects. When choosing a drug to treat levodopa-induced complications, it is important to consider the risks and benefits of the different classes and of the specific agents within each class, given the different efficacy and safety profiles of each.

Hair loss in women.

PubMed

Camacho-Martínez, Francisco M

2009-03-01

Female pattern hair loss (FPHL) is a clinical problem that is becoming more common in women. Female alopecia with androgen increase is called female androgenetic alopecia (FAGA) and without androgen increase is called female pattern hair loss. The clinical picture of typical FAGA begins with a specific "diffuse loss of hair from the parietal or frontovertical areas with an intact frontal hairline." Ludwig called this process "rarefaction." In Ludwig's classification of hair loss in women, progressive type of FAGA, 3 patterns were described: grade I or minimal, grade II or moderate, and grade III or severe. Ludwig also described female androgenetic alopecia with male pattern (FAGA.M) that should be subclassified according to Ebling's or Hamilton-Norwood's classification. FAGA.M may be present in 4 conditions: persistent adrenarche syndrome, alopecia caused by an adrenal or an ovarian tumor, posthysterectomy, and as an involutive alopecia. A more recent classification (Olsen's classification of FPHL) proposes 2 types: early- and late-onset with or without excess of androgens in each. The diagnosis of FPHL is made by clinical history, clinical examination, wash test, dermoscopy, trichoscan, trichograms and laboratory test, especially androgenic determinations. Topical treatment of FPHL is with minoxidil, 2-5% twice daily. When FPHL is associated with high levels of androgens, systemic antiandrogenic therapy is needed. Persistent adrenarche syndrome (adrenal SAHA) and alopecia of adrenal hyperandrogenism is treated with adrenal suppression and antiandrogens. Adrenal suppression is achieved with glucocorticosteroids. Antiandrogens therapy includes cyproterone acetate, drospirenone, spironolactone, flutamide, and finasteride. Excess release of ovarian androgens (ovarian SAHA) and alopecia of ovarian hyperandrogenism is treated with ovarian suppression and antiandrogens. Ovarian suppression includes the use of contraceptives containing an estrogen, ethinylestradiol, and a progestogen. Antiandrogens such as cyproterone acetate, always accompanied by tricyclic contraceptives, are the best choice of antiandrogens to use in patients with FPHL. Gonadotropin-releasing hormone agonists such as leuprolide acetate suppress pituitary and gonadal function through a reduction in luteinizing hormone and follicle-stimulating hormone levels. Subsequently, ovarian steroid levels also will be reduced, especially in patients with polycystic ovary syndrome. When polycystic ovary syndrome is associated with insulin resistance, metformin must be considered as treatment. Hyperprolactinemic SAHA and alopecia of pituitary hyperandrogenism should be treated with bromocriptine or cabergoline. Postmenopausal alopecia, with previous high levels of androgens or with prostatic-specific antigen greater than 0.04 ng/mL, improves with finasteride or dutasteride. Although we do not know the reason, postmenopausal alopecia in normoandrogenic women also improves with finasteride or dutasteride at a dose of 2.5 mg per day. Dermatocosmetic concealment with a hairpiece, hair prosthesis as extensions, or partial hairpieces can be useful. Lastly, weight loss undoubtedly improves hair loss in hyperandrogenic women.

Clomiphene and other antioestrogens for ovulation induction in polycystic ovarian syndrome.

PubMed

Brown, Julie; Farquhar, Cindy

2016-12-15

Subfertility due to anovulation is a common problem in women. First-line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin-sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. Secondary outcomes were poorly reported.The quality of the evidence ranged from low to very low. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS)No data were reported for these outcomes. Clinical pregnancy rateClomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low-quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rateThere was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low-quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rateThere was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low-quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rateThere was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low-quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low-quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSSThere were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rateThere was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low-quality evidence). No data were reported for the other outcomes. Other comparisons of interestLimited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates.The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this.There was limited evidence suggesting that a 10-day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5-day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data.The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low-quality evidence suggested that a 10-day regimen of clomiphene citrate improves pregnancy rates compared with a 5-day regimen, but further research is required.

[Post-partum: Guidelines for clinical practice--Short text].

PubMed

Sénat, M-V; Sentilhes, L; Battut, A; Benhamou, D; Bydlowski, S; Chantry, A; Deffieux, X; Diers, F; Doret, M; Ducroux-Schouwey, C; Fuchs, F; Gascoin, G; Lebot, C; Marcellin, L; Plu-Bureau, G; Raccah-Tebeka, B; Simon, E; Bréart, G; Marpeau, L

2015-12-01

To determine the post-partum management of women and their newborn whatever the mode of delivery. The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. Because breastfeeding is associated with a decrease in neonatal morbidity (lower frequency of cardiovascular diseases, infectious, atopic or infantile obesity) (EL2) and an improvement in the cognitive development of children (EL2), exclusive and extended breastfeeding is recommended (grade B) between 4 to 6 months (Professional consensus). In order to increase the rate of breastfeeding initiation and its duration, it is recommended that health professionals work closely with mothers in their project (grade A) and to promote breastfeeding on demand (grade B). There is no scientific evidence to recommend non-pharmacological measures of inhibition of lactation (Professional consensus). Pharmacological treatments for inhibition of lactation should not be given routinely to women who do not wish to breastfeed (Professional consensus). Because of potentially serious adverse effects, bromocriptin is contraindicated in inhibiting lactation (Professional consensus). For women aware of the risks of pharmacological treatment of inhibition of lactation, lisuride and cabergolin are the preferred drugs (Professional consensus). Whatever the mode of delivery, numeration blood count is not systematically recommended in a general population (Professional consensus). Anemia must be sought only in women with bleeding or symptoms of anemia (Professional consensus). The only treatment of post-dural puncture headache is the blood patch (EL2), it must not be carried out before 48 h (Professional consensus). Women vaccination status and their family is to be assessed in the early post-partum (Professional consensus). Immediate postoperative monitoring after caesarean delivery should be performed in the recovery room, but in exceptional circumstances, it may be performed in the delivery unit provided safety rules are maintained and regulatory authorities are informed (Professional consensus). An analgesic multimodal protocol developed by the medical team should be available and oral way should be favored (Professional consensus) (grade B). For every cesarean delivery, thromboprophylaxis with elastic stockings applied on the morning of the surgery and kept for at least 7 postoperative days is recommended (Professional consensus) with or without the addition of LMWH according to the presence or not of additional risk factors, and depending on the risk factor (major, minor). Early postoperative rehabilitation is encouraged (Professional consensus). Postpartum visit should be planned 6 to 8 weeks after delivery and can be performed by an obstetrician, a gynecologist, a general practitioner or a midwife, after normal pregnancy and delivery (Professional consensus). Starting effective contraception later 21 days after delivery in women who do not want closely spaced pregnancy is recommended (grade B), and to prescribe it at the maternity (Professional consensus). According to the postpartum risk of venous thromboembolism, the combined hormonal contraceptive use before six postpartum weeks is not recommended (grade B). Rehabilitation in asymptomatic women in order to prevent urinary or anal incontinence in medium or long-term is not recommended (Expert consensus). Pelvic-floor rehabilitation using pelvic-floor muscle contraction exercises is recommended to treat persistent urinary incontinence at 3 months postpartum (grade A), regardless of the type of incontinence. Postpartum pelvic-floor rehabilitation is recommended to treat anal incontinence (grade C). Postpartum pelvic-floor rehabilitation is not recommended to treat or prevent prolapse (grade C) or dyspareunia (grade C). The optimal time for maternity discharge for low risk newborn depends more on the organisation of the post-discharge follow up (Professional consensus). The months following the birth are a transitional period, and psychological alterations concern all parents (EL2). It is more difficult in case of psychosocial risk factors (EL2). In situations of proven psychological difficulties, the impact on the psycho-emotional development of children can be important (EL3). Among these difficulties, postpartum depression is the most common situation. However, the risk is generally higher in the perinatal period for all mental disorders (EL3). Postpartum is, for clinicians, a unique and privileged opportunity to address the physical, psychological, social and somatic health of their patients. Copyright © 2015 Elsevier Masson SAS. All rights reserved.