Sample records for bromocriptine

  1. Bromocriptine (United States)

    ... too much growth hormone in the body) and Parkinson's disease (PD; a disorder of the nervous system that causes difficulties with movement, muscle control, and balance). Bromocriptine (Cycloset) is used with a diet and exercise program and sometimes with other medications to control ...

  2. Treating organic abulia with bromocriptine and lisuride: four case studies.


    Barrett, K


    Abulia refers to an impairment of will, or the inability to initiate behaviour and action. There are reports of successful treatment of akinetic mutism, the most severe form of abulia, with bromocriptine. Four case studies are presented describing the successful treatment of abulia at a lesser severity than akinetic mutism with bromocriptine. Abulia was caused by brain damage due to alcohol in two cases, Wilson's disease and basal ganglia infarct in one each. Maximum bromocriptine dose varied...

  3. Clinical efficacy of bromocriptine and the influence of serum ...

    African Journals Online (AJOL)

    Nouran Abdelaziz AbouKhedr


    May 18, 2013 ... studies have pointed to a potential therapeutic role of bromocriptine in psoriasis. ... upregulated in response to psychological and physical stress.6 ... Parkinsonism. Common side effects include nausea, headache, dizziness and fatigue.9 Several studies demonstrated the bene- ficial effects of bromocriptine ...

  4. Clinical efficacy of bromocriptine and the influence of serum ...

    African Journals Online (AJOL)

    Background: Psoriasis is a T-cell mediated hyperproliferative cutaneous disease of multifactorial etiology. Prolactin (PRL) has been implicated in the pathogenesis of psoriasis and several studies have pointed to a potential therapeutic role of bromocriptine in psoriasis. Aim: To assess the clinical efficacy of bromocriptine ...

  5. Treating organic abulia with bromocriptine and lisuride: four case studies. (United States)

    Barrett, K


    Abulia refers to an impairment of will, or the inability to initiate behaviour and action. There are reports of successful treatment of akinetic mutism, the most severe form of abulia, with bromocriptine. Four case studies are presented describing the successful treatment of abulia at a lesser severity than akinetic mutism with bromocriptine. Abulia was caused by brain damage due to alcohol in two cases, Wilson's disease and basal ganglia infarct in one each. Maximum bromocriptine dose varied from 25-70 mg. All improved considerably. Withdrawal or reduction of medication in three produced deterioration. The prescription of a neuroleptic drug had a similar effect in the fourth. One patient with a previous history developed a depressive relapse and so the drug was withdrawn and lisuride introduced. This produced a similar improvement. These cases highlight the value of identifying the syndrome of organic abulia and suggest that dopamine agonists may have a place in its treatment, though controlled studies are needed. PMID:1940945

  6. Bromocriptine augmentation therapy in a patient with Cotard's syndrome. (United States)

    Kondo, Shuko; Hayashi, Hiroshi; Eguchi, Takuya; Oyama, Takanobu; Wada, Tadashi; Otani, Koichi


    A 72-year-old female with bipolar I disorder developed Cotard's syndrome, i.e., various delusions of negation accompanied by severe depressive symptoms. She responded neither to the combination of antipsychotic drug and antidepressant nor to the lithium augmentation therapy. However, the delusions and depressive symptoms improved dramatically after the addition of bromocriptine 2.5-5 mg/day to the combination of clomipramine and lithium. This report suggests that bromocriptine augmentation therapy might be effective at least for some patients with Cotard's syndrome in mood disorders.

  7. Bromocriptine does not alter speed-accuracy tradeoff

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    Jasper eWinkel


    Full Text Available Being quick often comes at the expense of being accurate. This speed-accuracy tradeoff is a central feature of many types of decision making. It has been proposed that dopamine plays an important role in adjusting responses between fast and accurate behavior. In the current study we investigated the role of dopamine in perceptual decision making in humans, focusing on speed-accuracy tradeoff. Using a cued version of the random dot motion task, we instructed subjects to either make a fast or an accurate decision. We investigated decision making behavior in subjects who were given bromocriptine (a dopamine receptor agonist or placebo. We analyzed the behavioral data using two accumulator models, the drift diffusion model and the linear ballistic accumulator model. On a behavioral level, there were clear differences in decision threshold between speed and accuracy focus, but decision threshold did not differ between the drug and placebo sessions. Bayesian analyses support the null hypothesis that there is no effect of bromocriptine on decision threshold. On the neural level, we replicate previous findings that the striatum and pre-supplementary motor area are active when preparing for speed, compared with accurate decisions. We do not find an effect of bromocriptine on this activation. Therefore, we conclude that bromocriptine does not alter speed-accuracy tradeoff.

  8. Clinical efficacy of bromocriptine and the influence of serum ...

    African Journals Online (AJOL)

    Nouran Abdelaziz AbouKhedr


    May 18, 2013 ... Clinical efficacy of bromocriptine and the influence of serum prolactin levels on disease severity in patients with chronic plaque-type psoriasis. Nouran Abdelaziz AbouKhedr, Amira Abulfotooh Eid *. Department of Dermatology, Venereology and Andrology, Faculty of Medicine, University of Alexandria, ...

  9. The effects of lisuride, terguride and bromocriptine on intraocular pressure (IOP).


    Al-Sereiti, M R; Turner, P


    1. The effects of a single oral dose of the dopaminergic agonists lisuride (0.1 mg), terguride (0.25 mg) and bromocriptine (1.25 mg) on IOP were studied in eight normal volunteers using the non-contact tonometer. 2. Considering all post-dose measurements, compared with placebo, bromocriptine and lisuride but not terguride reduced IOP significantly in both eyes. 3. There was no significant difference between the ocular hypotensive effect of bromocriptine and lisuride. 4. Terguride reduced IOP ...

  10. The effects of lisuride, terguride and bromocriptine on intraocular pressure (IOP). (United States)

    Al-Sereiti, M R; Turner, P


    1. The effects of a single oral dose of the dopaminergic agonists lisuride (0.1 mg), terguride (0.25 mg) and bromocriptine (1.25 mg) on IOP were studied in eight normal volunteers using the non-contact tonometer. 2. Considering all post-dose measurements, compared with placebo, bromocriptine and lisuride but not terguride reduced IOP significantly in both eyes. 3. There was no significant difference between the ocular hypotensive effect of bromocriptine and lisuride. 4. Terguride reduced IOP significantly in the left eye at the 3 h time point after drug administration. 5. The result of this study confirms the reported ocular hypotensive effect of bromocriptine and showed that lisuride is as effective as bromocriptine in reducing IOP. 6. To evaluate the clinical importance of these drugs as ocular hypotensive agents other studies are needed using eye drops. PMID:2713211

  11. Caveolin-1 sensitizes rat pituitary adenoma GH3 cells to bromocriptine induced apoptosis

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    Huang Mu-Chiou


    Full Text Available Abstract Background Prolactinoma is the most frequent pituitary tumor in humans. The dopamine D2 receptor agonist bromocriptine has been widely used clinically to treat human breast tumor and prolactinoma through inhibition of hyperprolactinemia and induction of tumor cell apoptosis, respectively, but the molecular mechanism of bromocriptine induction of pituitary tumor apoptosis remains unclear. Caveolin-1 is a membrane-anchored protein enriched on caveolae, inverted flask-shaped invaginations on plasma membranes where signal transduction molecules are concentrated. Currently, caveolin-1 is thought to be a negative regulator of cellular proliferation and an enhancer of apoptosis by blocking signal transduction between cell surface membrane receptors and intracellular signaling protein cascades. Rat pituitary adenoma GH3 cells, which express endogenous caveolin-1, exhibit increased apoptosis and shrinkage after exposure to bromocriptine. Hence, the GH3 cell line is an ideal model for studying the molecular action of bromocriptine on prolactinoma. Results The expression of endogenous caveolin-1 in GH3 cells was elevated after bromocriptine treatment. Transiently expressed mouse recombinant caveolin-1 induced apoptosis in GH3 cells by enhancing the activity of caspase 8. Significantly, caveolin-1 induction of GH3 cell apoptosis was sensitized by the administration of bromocriptine. Phosphorylation of caveolin-1 at tyrosine 14 was enhanced after bromocriptine treatment, suggesting that bromocriptine-induced phosphorylation of caveolin-1 may contribute to sensitization of apoptosis in GH3 cells exposed to bromocriptine. Conclusion Our results reveal that caveolin-1 increases sensitivity for apoptosis induction in pituitary adenoma GH3 cells and may contribute to tumor shrinkage after clinical bromocriptine treatment.

  12. Efficacy of bromocriptine on glycemic and metabolic control of prediabetic patients. (United States)

    Khalilzade, Saied Hossein; Aminorroaya, Ashraf; Hovsepain, Silva; Amini, Masoud


    It is suggested that bromocriptine could be effective in treatment of prediabetic patients and, consequently, in preventing type 2 diabetes (T2DM). In this study, we investigated the effectiveness of bromocriptine on glycemic and metabolic control of prediabetic patients. In this double-blind, placebo controlled trial study, prediabetic patients diagnosed during Isfahan Diabetes Prevention Project (IDPP) were enrolled. They randomized in two bromocriptine (2.5 mg) and placebo-treated groups, for 12 weeks. After physical examination, fasting plasma glucose (FPG), HbA1c, Insulin, cholesterol, HDL-c, and triglyceride were measured and glucose tolerance test (OGTT) was performed. HOMA-IR and LDL-c were calculated. The mean of the data were compared in the bromocriptine and placebo treated groups, before and after intervention by intention to treat analysis using mixed effect model. P values 0.05). The mean body mass index, systolic blood pressure, fasting plasma glucose and glucose of 30 min, 60 min, 120 min of post OGTT, HbA1c, insulin, HOMA-IR, lipid profile did not change, significantly, in both bromocriptine and placebo-treated groups after 12 weeks (P > 0.05). However, diastolic blood pressure (P = 0.02) and the area under the curve of glucose (P = 0.045) were decreased in the bromocriptine-treated group. Bromocriptine did not have significant effect on glycemic control of prediabetic patients. Further studies, with bigger sample size are recommended.

  13. Inhibition of SKP2 Sensitizes Bromocriptine-Induced Apoptosis in Human Prolactinoma Cells. (United States)

    Huang, Jinxiang; Zhang, Fenglin; Jiang, Lei; Hu, Guohan; Sun, Wei; Zhang, Chenran; Ding, Xuehua


    Prolactinoma (prolactin-secreting pituitary adenoma) is one of the most common estrogen-related functional pituitary tumors. As an agonist of the dopamine D2 receptor, bromocriptine is used widely to inhibit prolactinoma progression. On the other hand, it is not always effective in clinical application. Although a dopamine D2 receptor deficiency contributes to the impaired efficiency of bromocriptine therapy to some extent, it is unknown whether there some other underlying mechanisms leading to bromocriptine resistance in prolactinoma treatment. That is the main point addressed in this project. Human prolactinoma samples were used to analyze the S-phase kinase associated protein 2 (SKP2) expression level. Nutlin-3/adriamycin/cisplatin-treated GH3 and MMQ cells were used to analyze apoptosis in SKP2 overexpression or knockdown cells. SKP2 expression and the interaction partners of SKP2 were also detected after a bromocriptine treatment in 293T. Apoptosis was analyzed in C25 and bromocriptine-treated GH3 cells. Compared to normal pituitary samples, most prolactinoma samples exhibit higher levels of SKP2 expression, which could inhibit apoptosis in a p53-dependent manner. In addition, the bromocriptine treatment prolonged the half-life of SKP2 and resulted in SKP2 overexpression to a greater extent, which in turn compromised its pro-apoptotic effect. As a result, the bromocriptine treatment combined with C25 (a SKP2 inhibitor) led to the maximal apoptosis of human prolactinoma cells. These findings indicated that SKP2 inhibition sensitized the prolactinoma cells to bromocriptine and helped promote apoptosis. Moreover, a combined treatment of bromocriptine and C25 may contribute to the maximal apoptosis of human prolactinoma cells.

  14. Lisuride versus bromocriptine treatment in Parkinson disease: a double-blind study. (United States)

    LeWitt, P A; Gopinathan, G; Ward, C D; Sanes, J N; Dambrosia, J M; Durso, R; Calne, D B


    Twenty-eight parkinsonian patients were studied in a double-blind, crossover comparison of lisuride and bromocriptine. All but two patients completed the study, with each drug adjusted to an optimal dose (mean daily intake of 4.5 mg for lisuride and 56.5 mg for bromocriptine). Treatment with each drug was given for 7 to 10 weeks; three assessments were made at biweekly intervals with optimal dose levels. Conventional antiparkinsonian medications, including levodopa, were not changed. Efficacy and adverse effects were assessed by objective and subjective techniques. The only significant difference was slightly better control of akinesia with bromocriptine. There was considerable variability in the optimal dose of each drug, though the clinical profile of lisuride was quite similar to that of bromocriptine.

  15. The role of hypertension in bromocriptine-related puerperal intracranial hemorrhage

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    Kirsch, C. [Dept. of Radiology, University Hospital, Newark, NJ (United States); Iffy, L. [Dept. of Obstetrics, Gynecology and Womens Health, University Hospital, Newark, NJ (United States); Zito, G.E. [Dept. of Neurology, University Hospital, Newark, NJ (United States); McArdle, J.J. [Dept. of Pharmacology, University Hospital, Newark, NJ (United States)


    The spate of medicolegal inquiries following the disqualification of Parlodel (bromocriptine mesylate) by the Food and Drug Administration for postpartum ablactation, uncovered previously unreported side effects associated with its postpartum administration. In 1994, bromocriptine mesylate was withdrawn from the market as a milk suppressant. Since this time, over a dozen cases of postpartum intracranial hemorrhages associated with its use have been reported. We describe three additional cases of postpartum intracranial hemorrhage related to bromocriptine usage. One patient, previously normotensive, developed hypertension and a headache; initial CT was normal, but CT 24 h later demonstrated intracranial hemorrhage. This suggests that the blood-pressure elevation was drug-induced and was the cause, rather than the consequence, of bromocriptine-related intracranial hemorrhage. (orig.)

  16. Comparison of the efficacy of lisuride versus bromocriptine in the treatment of hyperprolactinemia


    Erenus, M.; Kır, M.; Kutlay, L.C.; Pekin, S.


    Dopamine agonists have been succesfully used in the treatment of various clinical disorders associated with hyperprolactinemia. However all of them are associated with some side effects which differ in incidence and severity. We have compared the efficacy and side effects of lisuride with bromocriptine in the treatment of hyperprolactinemia.Twenty women with hyperprolactinemia were randomized to receive either oral lisuride or bromocriptine. Ten patients received lisuride 0.2 mg b.i.d. and ot...

  17. Lisuride versus bromocriptine for levodopa-induced complications in Parkinson's disease. (United States)

    Clarke, C E; Speller, J M


    To compare the efficacy and safety of adjunct lisuride therapy versus bromocriptine in patients with Parkinson's disease, already established on levodopa and suffering the long-term complications of therapy. Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Cambridge Laboratories, Roche Products Limited and Sandoz Limited. Randomised controlled trials of lisuride versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. Data was abstracted independently by each author and differences settled by discussion. Only one randomised cross-over trial including 20 patients has compared lisuride with bromocriptine as adjunct therapy in Parkinson's disease. Both lisuride and bromocriptine improved motor fluctuations with no significant differences between the agonists. However, this conclusion is based on an unvalidated 4 point rating scale which could only record positive outcomes. This, combined with the small size of the trial, suggests that firm conclusions on motor fluctuations should not be drawn. Lisuride and bromocriptine produced similar benefits in parkinsonian impairments according to the Columbia Rating Scale. Adverse events were similar with the two agonists and no withdrawals were reported from either drug. The small size of this study and other methodological problems do not allow any firm conclusions to be drawn regarding the efficacy and safety of lisuride compared with bromocriptine in advanced Parkinson's disease with motor complications.

  18. Bromocriptine-Induced Hyperglycemia in Nonobese Diabetic Mice: Kinetics and Mechanisms of Action (United States)

    Durant, Sylvie; Coulaud, Josiane; Homo-Delarche, Francoise


    The effects of bromocriptine (10 mg/kg), known to inhibit prolactin secretion and lower autoimmune processes, were studied on glucose homeostasis in non-fasted non-obese diabetic mice, a spontaneous model of type 1 diabetes. Hyperglycemia was observed 120 and 240 min after i.p. but not s.c. injection. Bromocriptine administration i.p. led to rapid and marked hyperglycemia characterized by sexual dimorphism with males having higher glycemia than females. Bromocriptine induced a rapid but transient decrease in insulinemia in males only and biphasic increases in glucagon levels and a sustained stimulatory effect on circulating corticosterone in both sexes. Bromocriptine-induced hyperglycemia involved D2-dopaminergic receptors, as demonstrated by the inhibitory effect of the D2-dopamine antagonist, metoclopramide (10 mg/kg). Simultaneous injection of bromocriptine and metoclopramide also blocked the rise in blood corticosterone. In conclusion, by inducing hyperglycemia, i.p. bromocriptine administration to prediabetic autoimmune mice may counteract its beneficial anti-immunostimulatory effects. PMID:18084676

  19. Effect of bromocriptine-QR (a quick-release formulation of bromocriptine mesylate) on major adverse cardiovascular events in type 2 diabetes subjects. (United States)

    Gaziano, J Michael; Cincotta, Anthony H; Vinik, Aaron; Blonde, Lawrence; Bohannon, Nancy; Scranton, Richard


    Bromocriptine-QR (a quick-release formulation of bromocriptine mesylate), a dopamine D2 receptor agonist, is a US Food and Drug Administrration-approved treatment for type 2 diabetes mellitus (T2DM). A 3070-subject randomized trial demonstrated a significant, 40% reduction in relative risk among bromocriptine-QR-treated subjects in a prespecified composite cardiovascular (CV) end point that included ischemic-related (myocardial infarction and stroke) and nonischemic-related (hospitalization for unstable angina, congestive heart failure [CHF], or revascularization surgery) end points, but did not include cardiovascular death as a component of this composite. The present investigation was undertaken to more critically evaluate the impact of bromocriptine-QR on cardiovascular outcomes in this study subject population by (1) including CV death in the above-described original composite analysis and then stratifying this new analysis on the basis of multiple demographic subgroups and (2) analyzing the influence of this intervention on only the "hard" CV end points of myocardial infarction, stroke, and CV death (major adverse cardiovascular events [MACEs]). Three thousand seventy T2DM subjects on stable doses of ≤2 antidiabetes medications (including insulin) with HbA1c ≤10.0 (average baseline HbA1c=7.0) were randomized 2:1 to bromocriptine-QR (1.6 to 4.8 mg/day) or placebo for a 52-week treatment period. Subjects with heart failure (New York Heart Classes I and II) and precedent myocardial infarction or revascularization surgery were allowed to participate in the trial. Study outcomes included time to first event for each of the 2 CV composite end points described above. The relative risk comparing bromocriptine-QR with the control for the cardiovascular outcomes was estimated as a hazard ratio with 95% confidence interval on the basis of Cox proportional hazards regression. The statistical significance of any between-group difference in the cumulative percentage of

  20. Positive prolactin response to bromocriptine in 2 patients with cabergoline-resistant prolactinomas. (United States)

    Iyer, Pallavi; Molitch, Mark E


    To describe a positive prolactin response to bromocriptine treatment in 2 patients with cabergoline-resistant prolactinomas. We report the patients' clinical presentations, laboratory test results, imaging findings, and clinical courses. Patient 1 had a 5-mm pituitary microadenoma that was initially diagnosed at age 30 years. After initial diagnosis, she was treated with transvaginal bromocriptine for 9 years and then subsequently went untreated for 2 years. After developing symptoms of amenorrhea, decreased libido, and hyperprolactinemia, oral cabergoline, 0.5 mg twice weekly, was initiated. Her prolactin concentration remained elevated at 80 ng/mL while taking cabergoline. Her prolactin concentration decreased to 13 ng/mL after her regimen was switched to bromocriptine, 5 mg daily. Patient 2 had a 17-mm pituitary macroadenoma that was initially diagnosed at age 15 years. Oral cabergoline was started at 0.5 mg twice weekly and increased to 1 mg 3 times weekly when prolactin levels continued to rise to 340 ng/mL over 18 months. After visual field defects developed, transsphenoidal surgery was performed. One year after surgery, magnetic resonance imaging showed a 6- to 7-mm pituitary adenoma, and there was a gradual rise in serum prolactin. Her serum prolactin concentration continued to rise to 212 ng/mL with increasing tumor size over 3 years. Cabergoline was discontinued and oral bromocriptine was initiated at a dosage of 10 mg daily. After 4.5 months of bromocriptine therapy, her serum prolactin concentration decreased to 133 ng/mL. However, after 2 months, the macroadenoma continued to increase in size and a visual field defect developed, so another transsphenoidal operation was performed. Although cabergoline is generally preferred to bromocriptine for the treatment of patients with prolactinomas because of its better tolerance profile and greater effectiveness, in patients with cabergoline-resistant prolactinomas, a bromocriptine trial should be considered a

  1. Protective effects of baicalin against bromocriptine induced abortion in mice. (United States)

    Ma, Ai-Tuan; Zhong, Xiu-Hui; Liu, Zhan-Min; Shi, Wan-Yu; Du, Jian; Zhai, Xiang-He; Zhang, Tie; Meng, Li-Gen


    The Chinese herbal medicine Huang Qin (Radix Scutellariae) had been used for restless fetus for hundreds of years in China, however, little attention had been given to the components of the herb, specifically its ability to exert abortion-preventing effects at the maternal fatal interface. The present study was carried out to investigate the protective effects of baicalin and the possible mechanisms on pregnancies. Baicalin (at 10, 20, and 50 mg/kg BW respectively) was gavaged to bromocriptine-treated mice from gestation day (GD) 1 through GD 7. Abortion rates were calculated and the changes of interferon-gamma (IFN-gamma), interleukin-10 (IL-10) and progesterone were assayed on different gestation days. Results showed that the embryonic death rates were significantly decreased in groups supplemented with 20 or 50 mg/kg BW of baicalin, accompanied with reduced IFN-gamma and enhanced progesterone contents. Moreover, the highest levels of IFN-gamma appeared on GD 5 both in the control and in baicalin treated groups. It is concluded that baicalin can exert an anti-abortive effect by cutting down the production of IFN-gamma and elevating the levels of progesterone in a dose dependent manner and IFN-gamma is involved in an inflammatory reaction which is beneficial for a successful implantation.

  2. Efficacy and Safety of Bromocriptine-QR in Type 2 Diabetes: A Systematic Review and Meta-Analysis. (United States)

    Liang, W; Gao, L; Li, N; Wang, B; Wang, L; Wang, Y; Yang, H; You, L; Hou, J; Chen, S; Zhu, H; Jiang, Y; Pan, H


    Bromocriptine-QR (quick release) is a novel treatment for type 2 diabetes. The objective of this study is to assess the efficacy and safety of bromocriptine-QR in adults with type 2 diabetes mellitus based on randomized controlled trials published in peer-reviewed journals or as abstracts. We performed a comprehensive literature search of MEDLINE, Pubmed, Web of Science, EMBASE, and the Cochrane Library up to May 2015. Randomized controlled trials of bromocriptine-QR therapy in type 2 diabetes mellitus were eligible. Two reviewers independently assessed the eligibility of trials based on predefined inclusion criteria. Information was collected concerning basic study data, patient characteristics, efficacy and safety outcomes, and methodological quality. Bromocriptine-QR add-on therapy lowered hemoglobin A1c compared with placebo (weighted mean difference, - 6.52 mmol/mol; 95% CI, - 8.07 to - 4.97 mmol/mol). Bromocriptine-QR exhibited an increase in achieving an HbA1c level ≤ 53 mmol/mol (≤ 7.0%) (32.0 vs. 9.5%; odds ratio, 4.57; 95% CI, 2.42-8.62). Fasting plasma glucose was reduced with bromocriptine-QR compared with placebo (weighted mean difference,-1.04 mmol/l; 95% CI,-1.49 to-0.59 mmol/l). Moreover, bromocriptine-QR had neutral effects on postprandial glycemia, Body Mass Index (BMI), and lipid profile. Bromocriptine-QR had more gastrointestinal side effects of nausea and vomiting. Bromocriptine-QR had no increased risk of hypoglycemia, hypotension, or cardiovascular effects. Bromocriptine-QR therapy offers an alternative option to currently available antidiabetic agents for type 2 diabetes mellitus adults. Neither hypoglycemia nor other metabolic changes occur with this drug. More data for long-term efficacy and safety are needed for further observation. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Effect of bromocriptine alginate nanocomposite (BANC) on a transgenic Drosophila model of Parkinson's disease


    Yasir Hasan Siddique; Wasi Khan; Ambreen Fatima; Smita Jyoti; Saba Khanam; Falaq Naz; Rahul,; Fahad Ali; Braj Raj Singh; Alim Hussain Naqvi


    ABSTRACT The effect of bromocriptine, a dopamine agonist, administered in the form of bromocriptine alginate nanocomposite (BANC) was studied on Parkinson's disease (PD) model flies. The synthesized BANC was subject to characterization and, at a final concentration of 0.5, 1.0 and 1.5??M, was mixed in diet. The PD flies were allowed to feed on it for 24?days. A significant dose-dependent delay in the loss of climbing activity and activity pattern was observed in PD flies exposed to 0.5, 1.0 a...

  4. Increased prevalence of subclinical cardiac valve fibrosis in patients with prolactinomas on long-term bromocriptine and cabergoline treatment. (United States)

    Elenkova, Atanaska; Shabani, Rabhat; Kalinov, Krassimir; Zacharieva, Sabina


    In contrast to cabergoline, evidence-based information about a possible profibrotic effect of bromocriptine in prolactinoma patients is extremely limited. To assess the prevalence of valvular lesions among patients on long-term bromocriptine or cabergoline therapy. Case-control study. A transthoracic echocardiographic evaluation was performed in 334 subjects divided into four groups: 103 cabergoline treated, 55 bromocriptine treated, 74 naïve patients, and 102 controls. Clinically relevant valve regurgitations were equally prevalent in all investigated groups whereas subclinical valve fibrosis was significantly more frequent in both bromocriptine- and cabergoline-treated patients (40 vs 43.6 vs 21.6 vs 23.5%; P=0.004). The odds ratio (OR) for developing valvular fibrosis was 2.27 (95% CI 1.17-4.41; P=0.016) for cabergoline and 2.66 (95% CI 1.22-5.78; P=0.014) for bromocriptine groups compared with subjects not exposed to dopamine agonists (DAs). A significantly higher pulmonary arterial pressure corresponding to the longer treatment duration was observed among patients taking bromocriptine compared with cabergoline-treated subjects. Long-term treatment with cabergoline and bromocriptine seems not to be associated with an increased risk of clinically significant valve disease but possible subclinical lesions should be expected. An echocardiographic examination is recommended at the beginning and periodically during therapy with DAs acting as full or partial agonists of 5-hydroxytrytamine 2B receptors (cabergoline and bromocriptine). Bromocriptine seems not to be a safe alternative for patients receiving cabergoline treatment who have preexisting or diagnosed abnormalities suggesting valvular, interstitial myocardial, or pulmonary fibrosis. Further studies are needed to investigate the possible impact of DA treatment on pulmonary arterial pressure.

  5. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

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    Clow, D.W.; Hammer, R.P. Jr. (Univ. of Hawaii School of Medicine, Honolulu (USA))


    2-(14C)deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine.

  6. Prevention of breast pain and milk secretion with bromocriptine after second-trimester abortion

    DEFF Research Database (Denmark)

    Nyboe Andersen, A; Damm, P; Tabor, A


    .01), in serum prolactin (PRL) (p less than 0.001) and in the subjective assessment score of breast pain (p less than 0.01) and milk secretion (p less than 0.01). Alleviation of breast pain and prevention of milk secretion appears to be indicated after second-trimester abortion, and treatment with bromocriptine...

  7. Focusing on cardiovascular disease in type 2 diabetes mellitus: an introduction to bromocriptine QR. (United States)

    Bell, David S


    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.

  8. Body weight changes in female patients with prolactinoma treated with bromocriptin

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    Z. Velija-Ašimi;


    Full Text Available The aim of this study was to determine the body weight changes in female patients with bromocriptin treated prolactinoma. Seventeen hyperprolactinemic pre-menopausal female with prolactinoma, aged 18-45 years, with body mass index (BMI 30+/-2,1kg/m2 were included. Basal insulin level was measured in all patients as well as concentrations of luteinizing hormone (LH, follicle-stimulating hormone (FSH, estrogens, testosterone, thyroid-stimulating hormone (TSH and prolactin (PRL. All patients were treated with bromocriptine. PRL levels significantly decreased after six months of the treatment (3543+/-1211 vs.1130+/-588 μIU/ml, p<0.05. After a year of the treatment PRL level was normalized (560+/-297 μIU/ml. Mean body weight did not significantly change during the first 6 months but after a two-year period it significantly decreased (27.6+/-1,4kg/m2. Waist/hip ratio did not significantly change. Normalization of menstrual cycle and libido was obtained in all patients. The results of this study suggest that hyperprolactinemia may be regarded as a reversible cause of obesity in female patients with prolactinoma, and bromocriptin has an important role in the weight loss and insulin decreasing and normalization of gonadotropin secretion as well.

  9. Evaluation of the efficacy and safety of bromocriptine QR in type 2 diabetes. (United States)

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


    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.

  10. Different effects of cabergoline and bromocriptine on metabolic and cardiovascular risk factors in patients with elevated prolactin levels. (United States)

    Krysiak, Robert; Okopien, Bogusław


    Hyperprolactinaemia is suggested to be associated with metabolic and hormonal complications. No previous study has compared the effect of different dopamine agonists on plasma lipids, carbohydrate metabolism markers and cardiovascular risk factors in patients with elevated prolactin levels. The study included eight bromocriptine-resistant women with prolactinoma (group 1) and twelve matched women with hyperprolactinaemia unrelated to prolactinoma (group 2). Group 1 was then treated with cabergoline, while group 2 with bromocriptine. Plasma lipids, glucose homeostasis markers and plasma levels of prolactin, insulin-like growth factor-1 (IGF-1) and cardiovascular risk factors were assessed before and after 6 months of therapy. Both treatments normalized plasma prolactin levels. Cabergoline reduced triglycerides, 2-hr post-challenge plasma glucose, the homeostatic model assessment of insulin resistance (HOMA-IR), and circulating levels of IGF-1, free fatty acids (FFA), uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen, as well as increased HDL cholesterol and 25-hydroxyvitamin D. With the exception of a reduction in HOMA-IR, bromocriptine treatment produced no significant effect on the investigated biomarkers. Cabergoline was superior to bromocriptine in affecting 2-hr post-challenge plasma glucose levels, HOMA-IR, as well as circulating levels of IGF-1, FFA, uric acid, hsCRP, homocysteine, fibrinogen and 25-hydroxyvitamin D. Our results may suggest that cabergoline is superior to bromocriptine when it comes to affecting atherogenic dyslipidaemia, insulin sensitivity and circulating levels of cardiovascular risk factors in hyperprolactinaemic patients. These findings seem to support previous observations that cabergoline may be a better treatment for patients with elevated prolactin levels than bromocriptine. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  11. Bromocriptine and lisuride stimulate the accumulation of cyclic AMP in intact slices but not in homogenates of rat neostriatum. (United States)

    Saiani, L; Trabucchi, M; Tonon, G C; Spano, P F


    The effects of bromocriptine and lisuride on cyclic AMP concentrations in homogenates and in intact slices of rat neostriatum were investigated. Significant increases in cyclic AMP concentration were found after a 10-min exposure to bromocriptine and lisuride in striatal intact slices. On the contrary, as previously found, the two dopaminergic ergot derivatives did not stimulate dopamine-senstiive adenylate cyclase present in striatal homogenates. The stimulatory effects observed only in intact tissues were blocked by the specific dopamine receptor blocking agent fluphenazine. It is tempting to conclude that dopaminergic ergot derivatives have a site of action different from that stimulated by classic dopamine agonists in tissue homogenates.

  12. Ropinirole as an adjunct to levodopa in the treatment of Parkinson's disease: a 16-week bromocriptine controlled study. (United States)

    Im, Joo-Hyuk; Ha, Jeong-Ho; Cho, In-Sook; Lee, Myoung C


    and objectives Ropinirole is a non-ergoline, selective dopamine D(2) agonist. The aim of this study was to evaluate the efficacy and safety of ropinirole as an adjunct to levodopa in the treatment of Parkinson's disease (PD) complicated by motor fluctuations. A total of 76 patients with PD (Hoehn and Yahr stage II to IV) were included in this trial. Each patient was randomly allocated to receive either ropinirole (n = 37) or bromocriptine (n = 39) as an adjunct to levodopa over a 16-week period. Ropinirole and bromocriptine were titrated for optimal efficacy and tolerability. This optimal dose was then maintained for the rest of the study. Response rate was defined as the percentage of patients who achieved at least a 20 % reduction in levodopa dose. Clinical status was also assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Clinical Global Impression (CGI), and reduction in time spent 'off'. Ropinirole produced a significantly greater response rate than bromocriptine (odds ratio 2.995, 95 % C. I. (1.157, 7.751) p < 0.05). There was also a statistically significant difference between the groups in the proportion of patients who were 'improved' on the CGI improvement scale (91.9 % for ropinirole, 74.3 % for bromocriptine, p = 0.046). Other measures, including at least a 20 % improvement in the UPDRS motor score (70 % for ropinirole and 63.3 % for bromocriptine), and a 20 % reduction in 'off' duration (81 % for ropinirole and 52.4 % for bromocriptine) showed a trend in favour of ropinirole. There was no significant difference between the two groups in the overall incidence of adverse effects (ropinirole, 59.5 %; bromocriptine, 59 %). In each group, the most common side-effects were dizziness, dyskinesia and nausea/vomiting. No patients were withdrawn from the study because of side-effects. Ropinirole was found to be safe and well-tolerated. Ropinirole as an adjunct to levodopa in the treatment of PD with motor fluctuation was associated with more

  13. Effect of bromocriptine alginate nanocomposite (BANC) on a transgenic Drosophila model of Parkinson's disease. (United States)

    Siddique, Yasir Hasan; Khan, Wasi; Fatima, Ambreen; Jyoti, Smita; Khanam, Saba; Naz, Falaq; Rahul; Ali, Fahad; Singh, Braj Raj; Naqvi, Alim Hussain


    The effect of bromocriptine, a dopamine agonist, administered in the form of bromocriptine alginate nanocomposite (BANC) was studied on Parkinson's disease (PD) model flies. The synthesized BANC was subject to characterization and, at a final concentration of 0.5, 1.0 and 1.5 µM, was mixed in diet. The PD flies were allowed to feed on it for 24 days. A significant dose-dependent delay in the loss of climbing activity and activity pattern was observed in PD flies exposed to 0.5, 1.0 and 1.5 µM BANC. The PD flies exposed to BANC also showed a significant reduction in lipid peroxidation and glutathione-S-transferase activity, and an increase in glutathione content. However, no gross morphological changes were observed in the brains of PD flies compared with controls. The results suggest that BANC is effective in reducing the PD symptoms in these transgenic flies. © 2016. Published by The Company of Biologists Ltd.

  14. Effect of bromocriptine alginate nanocomposite (BANC on a transgenic Drosophila model of Parkinson's disease

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    Yasir Hasan Siddique


    Full Text Available The effect of bromocriptine, a dopamine agonist, administered in the form of bromocriptine alginate nanocomposite (BANC was studied on Parkinson's disease (PD model flies. The synthesized BANC was subject to characterization and, at a final concentration of 0.5, 1.0 and 1.5 µM, was mixed in diet. The PD flies were allowed to feed on it for 24 days. A significant dose-dependent delay in the loss of climbing activity and activity pattern was observed in PD flies exposed to 0.5, 1.0 and 1.5 µM BANC. The PD flies exposed to BANC also showed a significant reduction in lipid peroxidation and glutathione-S-transferase activity, and an increase in glutathione content. However, no gross morphological changes were observed in the brains of PD flies compared with controls. The results suggest that BANC is effective in reducing the PD symptoms in these transgenic flies.

  15. Effectively managing intractable central hyperthermia in a stroke patient by bromocriptine: a case report

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    Yu KW


    Full Text Available Kuo-Wei Yu,1,* Yu-Hui Huang,2,3 Chien-Lin Lin,1,4,* Chang-Zern Hong,5 Li-Wei Chou1,41Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; 2School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 3Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung, Taiwan; 4School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 5Department of Physical Therapy, Hungkuang University, Taichung, Taiwan*These authors contributed equally to this workAbstract: Central hyperthermia is characterized by a rapid onset, high temperature, marked temperature fluctuation, and poor response to antipyretics and antibiotics. Although poststroke central hyperthermia is common, prolonged instances are rare. We report a case of prolonged central fever after an intracranial hemorrhage. Before the accurate diagnosis and management of central fever, the patient underwent long-term antibiotic use that led to pseudomembranous colitis. Bromocriptine was used to treat the prolonged central hyperthermia, after which the fever did not exceed 39°C. A week later, the body temperature baseline was reduced to 37°C and a low-grade fever with minor temperature fluctuation occurred only a few times. No fever occurred in the month following the treatment. After the fever subsided, the patient could undergo an aggressive rehabilitation program.Keywords: bromocriptine, central hyperthermia, fever, stroke

  16. Kinetic profiling an abundantly expressed planarian serotonergic GPCR identifies bromocriptine as a perdurant antagonist

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    John D. Chan


    Full Text Available The diversity and uniqueness of flatworm G protein coupled receptors (GPCRs provides impetus for identifying ligands useful as tools for studying flatworm biology, or as therapeutics for treating diseases caused by parasitic flatworm infections. To catalyse this discovery process, technologies optimized for mammalian GPCR high throughput screening need be transposed for screening flatworm GPCRs. Here, we demonstrate the utility of a genetically encoded cAMP biosensor for resolving the properties of an abundantly expressed planarian serotonergic GPCR (S7.1R. Application of this methodology resolved the real time kinetics of GPCR modulation by ligands and demonstrated a marked difference in the kinetic action of antagonists at S7.1R. Notably, bromocriptine caused a protracted inhibition of S7.1R activity in vitro and a protracted paralysis of planarian movement, replicating the effect of S7.1R in vivo RNAi. The lengthy inhibition of function caused by bromocriptine at this abundantly expressed GPCR provides a useful tool to ablate serotonergic signaling in vivo, and is a noteworthy feature for exploitation as an anthelmintic vulnerability.

  17. Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice

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    Olakunle James Onaolapo


    Full Text Available This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.

  18. Treatment of hyperprolactinemic states with different drugs: a study with bromocriptine, metergoline, and lisuride. (United States)

    Crosignani, P G; Ferrari, C; Liuzzi, A; Benco, R; Mattei, A; Rampini, P; Dellabonzana, D; Scarduelli, C; Spelta, B


    One hundred ninety-one hyperprolactinemic patients (78 women and 13 men; 54 with pituitary macroadenoma, 53 with microadenoma, and 84 with idiopathic disease) were treated for 2 to 48 months with one or two of the following prolactin (PRL)-lowering drugs: bromocriptine, metergoline, and lisuride. All of the three drugs used were highly effective in lowering PRL levels and restoring gonadal function both in females and in males in the majority of patients with either idiopathic or tumorous disease. In poorly responsive patients, increasing the drug doses resulted in further PRL lowering for all the three drugs. Mild side effects were frequently encountered with initiation of drug treatment but spontaneously subsided in most cases; severe side effects, necessitating stopping of the treatment, occurred in only 12 instances, but changing of the drug allowed PRL-lowering treatment to be continued in 11 of them.

  19. Single dose cabergoline versus bromocriptine in inhibition of puerperal lactation: randomised, double blind, multicentre study. European Multicentre Study Group for Cabergoline in Lactation Inhibition. (United States)


    OBJECTIVE--To compare the efficacy and safety of a single dose of 1 mg of cabergoline with that of bromocriptine 2.5 mg twice daily for 14 days in the inhibition of puerperal lactation. DESIGN--Prospective, randomised, double blind, parallel group, multicentre study. SETTING--University of hospital departments of obstetrics and gynaecology in different European countries. SUBJECTS--272 puerperal women not wishing to lactate (136 randomised to each drug). INTERVENTIONS--Women randomised to cabergoline received two 0.5 mg tablets of cabergoline and one placebo tablet within 27 hours after delivery and then placebo twice daily for 14 days. Those randomised to bromocriptine received 2.5 mg of bromocriptine and two placebo tablets within 27 hours and then 2.5 mg of bromocriptine twice daily for 14 days. MAIN OUTCOME MEASURES--Success of treatment (complete or partial) according to milk secretion, breast engorgement, and breast pain; rebound symptomatology; serum prolactin concentrations; and number of adverse events. RESULTS--Complete success was achieved in 106 of 136 women randomised to cabergoline and in 94 of 136 randomised to bromocriptine and partial success in 21 and 33 women respectively. Rebound breast symptomatology occurred respectively in five and 23 women with complete success up to day 15 (p less than 0.0001). Serum prolactin concentrations dropped considerably with both drugs from day 2 to day 15; a prolactin secretion rebound effect was observed in women treated with bromocriptine. cabergoline and 36 receiving bromocriptine (p = 0.054), occurring most during the first treatment day. CONCLUSION--A single 1 mg dose of cabergoline is at least as effective as bromocriptine 2.5 mg twice daily for 14 days in preventing puerperal lactation. Because of the considerably lower rate of rebound breast activity and adverse events and the simpler administration schedule cabergoline should be the drug of choice for lactation inhibition. PMID:1676318

  20. Cabergoline versus bromocriptine in the treatment of hyperprolactinemia: a systematic review of randomized controlled trials and meta-analysis. (United States)

    dos Santos Nunes, Vania; El Dib, Regina; Boguszewski, César Luiz; Nogueira, Célia Regina


    Cabergoline and bromocriptine are the most used drugs in the treatment of hyperprolactinemia, they are able to normalize the prolactin levels, restore gonadal function and promote tumor reduction in the majority of patients. We undertake a systematic review and meta-analysis of randomized controlled trials to compare cabergoline versus bromocriptine in the treatment of patients with idiopathic hyperprolactinemia and prolactinomas. The data sources were: Embase, Pubmed, Lilacs and Cochrane Central. The outcome measures were: normalization of prolactin secretion, restoration of gonadal function, reduction of tumoral volume, quality of life and adverse drug effects. Were identified 418 references and after screening by title and abstract, we obtained complete copies of 34 articles potentially eligible for inclusion in the review. From this total, 19 were selected to be included, but fifteen of them were excluded due to the following reasons: one randomized study compared cabergoline versus placebo and other randomized study compared different doses of cabergoline; five references were cases series; four were only controlled studies; three were retrospectives series and; one was a cohort study. Therefore, four publications were included in the review and in the final analysis. The meta-analysis of normalization of serum prolactin levels and menstruation with return of ovulatory cycle showed a significant difference in favor of cabergoline group (RR 0.67 [CI 95% 0.57, 0.80]) e (RR 0.74 [CI 95% 0.67, 0.83]), respectively. The number of adverse effects was significantly higher in the bromocriptine number than in cabergoline group (RR 1.43 [CI 95% 1.03, 1.98]). The meta-analysis showed new evidence favoring the use of cabergoline in comparison with bromocriptine for the treatment of prolactinomas and idiopathic hyperprolactinemia.

  1. Bromocriptine treatment of microprolactinomas: evidence of stable prolactin decrease after drug withdrawal. (United States)

    Moriondo, P; Travaglini, P; Nissim, M; Conti, A; Faglia, G


    Thirty-six women with PRL-secreting pituitary microadenomas [mean PRL, 114 +/- 12.5 (+/- SE) ng/ml] were treated with bromocriptine (BRC; 2.5-10 mg/day) for 12 months. During BRC treatment, serum PRL decreased in all patients. After termination of treatment, mean serum PRL levels, evaluated at 15, 30, and 45 days, were significantly decreased (-41.6%, -43.0%, and -40.2%, respectively) compared to pretreatment values. The patients were arbitrarily divided into 3 groups: 12 responders, in whom the PRL persistent posttreatment decrease was greater than 50%, 8 hyporesponders, in whom the PRL decrease was between 30% and 50%, and 16 nonresponders with absent or negligible PRL decrease. Four patients had normal PRL levels and clinical remission for 14-30 months after BRC withdrawal. In 18 women, BRC treatment was repeated for another 12 months. After termination of treatment, 11 patients were responders, 1 was a hyporesponder, and 6 were nonresponders. Four of these 18 patients still had normal PRL levels 8-28 months after drug discontinuation. The responses of PRL to TRH and domperidone were compared before and after termination of treatment at 30 and 45 days, respectively. Both mean peak values of PRL and absolute increases after TRH treatment were similar before and after BRC administration; however, a PRL response to TRH was present in 15% of 26 patients before treatment and in 42% after treatment. The mean peak values after domperidone were similar before and after BRC treatment, but the absolute increase over the basal value was much higher after BRC; PRL response to domperidone was present in 16% of 19 patients before BRC treatment and in 74% after BRC. These data suggest that BRC is effective in the treatment of some microprolactinomas; BRC effectiveness improves after prolonged periods of administration. The variations in PRL responses to TRH and domperidone suggest profound modification of PRL secretion after BRC treatment.

  2. Effects of postnatal bromocriptine injection on thyroid function and prolactinemia of rats at adulthood. (United States)

    Carvalho, Janaine C; Lisboa, Patricia C; de Oliveira, Elaine; Peixoto-Silva, Nayara; Nobre, Jessica L; Fraga, Mabel C; Manhães, Alex C; Moura, Egberto G


    Previously, we demonstrated that maternal prolactin inhibition at the end of lactation, using bromocriptine (BRO), leads to an increase in leptin transfer via milk and induces the adult progeny to present hypothyroidism, leptin resistance and metabolic syndrome (obesity, hyperglycemia, hypertriglyceridemia, lower HDL). To test if these alterations are due to direct BRO action on the pups, in the present study we evaluated the long-term effects of direct injection of BRO (0.1μg/once daily) in male Wistar rats from postnatal (PN) day 1 to 10 (early treatment) or from PN11 to 20 (late treatment) on: food intake, body mass, cardiovascular parameters, hormone profile, hypothalamic leptin signaling, glucose homeostasis and thyroid hormone-dependent proteins. The respective controls were injected with methanol-saline. Offspring were killed at adulthood (PN180). Adult PN1-10 BRO-treated animals had lower food intake, hypoprolactinemia, lower leptin action (lower OBR-b, STAT-3 and SOCS-3 mRNA levels in the arcuate nucleus), lower TRH-TSH-thyroid axis as well as lower thyroid hormone markers. On the other hand, adult animals that were BRO-treated during the PN11-20 period showed hyperphagia, higher blood pressure, higher prolactinemia and OBR-b, higher TRH and plasma T3, hypercorticosteronemia as well as higher Dio2 and UCP1 mRNA expression in the brown adipose tissue. Glucose homeostasis was not changed treatment in either period. Our data show that early and late dopamine overexposure during lactation induces diverse metabolic disturbances later in life, increasing the risk of thyroid dysfunction and, consequently, changes in prolactinemia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. The role of bromocriptine-QR in the management of type 2 diabetes expert panel recommendations. (United States)

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


    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).

  4. Cardiovascular and Renal Effects of Bromocriptine in Diabetic Patients with Stage 4 Chronic Kidney Disease

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    Oliva Mejía-Rodríguez


    Full Text Available Objective. The objective of this study was to investigate the effect of bromocriptine (BEC on left ventricular mass index (LVMI and residual renal function (RRF in chronic kidney disease (CKD patients with type 2 diabetes (T2D. Research Design and Methods. A 6-month double-blind randomized controlled trial was conducted in 28 patients with T2D and stage 4 CKD with increased LVMI. Fourteen patients received BEC (2.5 mg, initially 1 tablet with subsequent increase to three times a day and 14 received a placebo (PBO; initially 1 tablet with subsequent increase to three times a day. Cardiovascular changes were assessed by monitoring 24 h ambulatory blood pressure, two-dimensional-guided M-mode echocardiography, and N-terminal brain natriuretic peptide (NT-proBNP plasma levels. RRF was evaluated by creatinine clearance and cystatin-C plasma levels. Results. Both BEC and PBO groups decreased blood pressure—but the effect was more pronounced in the BEC group. Average 24 h, diurnal and nocturnal blood pressures, and circadian profile showed improved values compared to the PBO group; LVMI decreased by 14% in BEC and increased by 8% in PBO group. NT-proBNP decreased in BEC (0.54±0.15 to 0.32±0.17 pg/mL and increased in PBO (0.37±0.15 to 0.64±0.17 pg/mL. Creatinine clearance did not change in the BEC group and decreased in the PBO group. Conclusions. BEC resulted in a decrease on blood pressure and LVMI. BEC also prevented the progression of CKD while maintaining the creatinine clearance unchanged.

  5. Effects of bromocriptine on serum prolactin levels, pituitary weight and immunoreactive prolactin cells in estradiol-treated ovariectomized rats: an experimental model of estrogen-dependent hyperprolactinemia

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    M.F. Ribeiro


    Full Text Available The present study was designed to assess the effects of bromocriptine, a dopamine agonist, on pituitary wet weight, number of immunoreactive prolactin cells and serum prolactin concentrations in estradiol-treated rats. Ovariectomized Wistar rats were injected subcutaneously with sunflower oil vehicle or estradiol valerate (50 or 300 µg rat-1 week-1 for 2, 4 or 10 weeks. Bromocriptine (0.2 or 0.6 mg rat-1 day-1 was injected daily during the last 5 or 12 days of estrogen treatment. Data were compared with those obtained for intact control rats. Administration of both doses of estrogen increased serum prolactin levels. No difference in the number of prolactin cells in rats treated with 50 µg estradiol valerate was observed compared to intact adult animals. In contrast, rats treated with 300 µg estradiol valerate showed a significant increase in the number of prolactin cells (P<0.05. Therefore, the increase in serum prolactin levels observed in rats treated with 50 µg estradiol valerate, in the absence of morphological changes in the pituitary cells, suggests a "functional" estrogen-induced hyperprolactinemia. Bromocriptine decreased prolactin levels in all estrogen-treated rats. The administration of this drug to rats previously treated with 300 µg estradiol valerate also resulted in a significant decrease in pituitary weight and number of prolactin cells when compared to the group treated with estradiol alone. The general antiprolactinemic and antiproliferative pituitary effects of bromocriptine treatment reported here validate the experimental model of estrogen-induced hyperprolactinemic rats

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

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


    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 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.

  7. Different Effects of Metformin on the Hypothalamic-Pituitary-Thyroid Axis in Bromocriptine- and Cabergoline-treated Patients with Hashimoto's Thyroiditis and Glucose Metabolism Abnormalities. (United States)

    Krysiak, R; Okrzesik, J; Okopien, B


    Metformin was found to reduce serum thyrotropin levels in patients with hypothyroidism. This effect was less pronounced if patients were additionally treated with bromocriptine. The study included 39 premenopausal women with autoimmune thyroiditis and thyrotropin levels exceeding 3.0 mU/L. All patients had been treated for at least 6 months with bromocriptine (5.0-7.5 mg daily) or cabergoline (0.5-1.0 mg weekly). Because of coexisting type 2 diabetes or impaired glucose tolerance, they were then given metformin (1.7-2.55 g daily). Glucose homeostasis markers, thyroid antibody titers, as well as serum levels of thyrotropin, total and free thyroid hormones and prolactin were determined before and after 6 months of metformin treatment. At baseline, cabergoline-treated patients were less insulin resistant as well as tended to have lower levels of prolactin than bromocriptine-treated patients. Although in both treatment groups, metformin decreased plasma levels of fasting and post-challenge plasma glucose and improved insulin receptor sensitivity, this effect was more prominent in patients receiving cabergoline. However, only in bromocriptine-treated patients, metformin decreased serum thyrotropin and this effect reached the level of significance in a subgroup of patients with subclinical hypothyroidism. Neither in cabergoline- nor in bromocriptine-treated patients, metformin affected thyroid hormone levels and thyroid antibody titers. Our results indicate that the effect of metformin on hypothalamic-pituitary-adrenal axis activity is partially determined by endogenous dopaminergic tone, thyrotrope activity and insulin sensitivity. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Aromatic Amino Acid Decarboxylase Deficiency Not Responding to Pyridoxine and Bromocriptine Therapy: Case Report and Review of Response to Treatment

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    Majid Alfadhel


    Full Text Available Aromatic L-amino acid decarboxylase (AADC deficiency (MIM #608643 is an autosomal recessive inborn error of monoamines. It is caused by a mutation in the DDC gene that leads to a deficiency in the AADC enzyme. The clinical features of this condition include a combination of dopamine, noradrenaline, and serotonin deficiencies, and a patient may present with hypotonia, oculogyric crises, sweating, hypersalivation, autonomic dysfunction, and progressive encephalopathy with severe developmental delay. We report the case of an 8-month-old boy who presented with the abovementioned symptoms and who was diagnosed with AADC deficiency based on clinical, biochemical, and molecular investigations. Treatment with bromocriptine and pyridoxine showed no improvement. These data support the findings observed among previously reported cohorts that showed poor response of this disease to current regimens. Alternative therapies are needed to ameliorate the clinical complications associated with this disorder.

  9. The effect of octreotide and bromocriptine on expression of a pro-apoptotic Bax protein in rat prolactinoma.

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    Jolanta Kunert-Radek


    Full Text Available It is well established that disruption of apoptosis may lead to tumor initiation, progression or metastasis. It is also well documented that many anticancer drugs induce apoptosis. In the earlier studies, the dopamine D2 receptor agonist bromocriptine (BC and somatostatin analog octreotide (OCT were found to inhibit the growth of the estrogen-induced rat prolactinoma. Our previous investigations, applying the TUNEL method showed the involvement of the pro-apoptotic effect in the action of BC, and to a lesser degree, in the action of OCT. The aim of the present study was to investigate whether the pro-apoptotic action of these drugs involves the increased expression of Bax--a member of Bcl-2 protein family which is known to play an important role in the regulation of apoptosis. Male four-week Fisher 344 rats were used in the experiment. Capsules containing diethylstilboestrol (DES were implanted subcutaneously. Six weeks after the implantation the rats were given OCT (2 x 25 microg/animal/24, BC (3 mg/kg b.w./24 h or OCT and BC at the above doses for 10 days. Bax expression was detected by immunohistochemistry. Prolactin (PRL in blood serum was measured by radioimmunoassay (RIA. It has been found that both OCT and BC, alone or in combination, significantly reduce the tumor weight. Both OCT and BC suppressed PRL levels, but the inhibitory effect of BC was stronger than that of OCT. It has been found that the treatment with OCT and BC, alone or in combination, causes a significant increase in Bax expression in the rat prolactinoma cells. Our findings indicate that anti-tumoral action of bromocriptine and to some extent the action of octreotide in the experimental rat prolactinoma is connected with the induction of apoptosis and is associated with increased Bax expression.

  10. Successful management of octreotide-insensitive thyrotropin-secreting pituitary adenoma with bromocriptine and surgery: A case report and literature review. (United States)

    Yang, Chengxian; Wu, Huanwen; Wang, Jing; Hu, Mingming; Xing, Xiaoping; Bao, Xinjie; Wang, Renzhi


    Case reports concerning the value of dopamine agonists in the treatment of patients with thyrotropin-secreting pituitary adenoma (TSHoma) are limited. Herein, we present a rare case of octreotide-insensitive TSHoma responding to bromocriptine therapy. A 45-year-old Chinese man was admitted to Peking Union Medical College Hospital with marked clinical manifestations of hyperthyroidism. Thyroid function tests demonstrated elevated concentrations of free thyroid hormones in the presence of normal thyrotropin. Magnetic resonance imaging findings showed a pituitary microadenoma on the right side of the sellar region. Based on characteristic endocrine results and neuroimaging findings, the patient was diagnosed with TSHoma. Most patients with TSHomas are significantly responsive to somatostatin analog treatment. However, our patient was orally administered with bromocriptine to normalize thyroid function as assessed by suppression tests conducted prior to surgery. A transsphenoidal surgery was performed by an experienced neurosurgeon for tumor removal. The pituitary lesion was totally resected. Following the operation, the results of thyroid function tests were immediately within reference limits. During the follow-up, there was no residual or recurrent tumor. Attention should be paid to the role of dopamine agonists such as bromocriptine and cabergoline as adjuvant therapy for TSHomas that are insensitive to traditional medical treatment by somatostatin analogs.

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

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


    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; PQR 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, PQR therapy for 24 weeks can provide significant added improvement in glycemic control relative to adding placebo.

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

    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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.; Wang, G.; Thanos, P.K.; Cho, J. Kim, R.; Michaelides, M.; Primeaux, S.; Bray, G.; Wang, G.-J.; Volkow, N.D.


    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 a 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.

  14. A six-month multicentre, double-blind, bromocriptine-controlled study of the safety and efficacy of ropinirole in the treatment of patients with Parkinson's disease not optimally controlled by L-dopa

    NARCIS (Netherlands)

    Brunt, ER; Brooks, DJ; Korczyn, AD; Montastruc, JL; Stocchi, F


    Objectives. To compare the safety and efficacy of ropinirole and bromocriptine as adjunct therapy in patients with Parkinson's disease (PD) not optimally controlled by L-dopa. Methods. A randomised, double-blind trial in which 555 patients were assigned to three treatment groups according to the

  15. Impact of bromocriptine-QR therapy on cardiovascular outcomes in type 2 diabetes mellitus subjects on metformin. (United States)

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


    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 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: Identifier: NCT00377676.

  16. 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. (United States)

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


    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. 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 HbA(1c), TDID, and postprandial glucose area under the curve of a four-hour mixed meal tolerance test (MMTT). 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 AUC(60-240) decreased 32% (P = 0.04) over the treatment period. The decline in HbA(1c) and TDID was observed at 8 weeks and sustained over the remaining 16-week study duration. 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.

  17. Identification and validation of the dopamine agonist bromocriptine as a novel therapy for high-risk myelodysplastic syndromes and secondary acute myeloid leukemia. (United States)

    Liberante, Fabio Giuseppe; Pouryahya, Tara; McMullin, Mary-Frances; Zhang, Shu-Dong; Mills, Kenneth Ian


    Myelodysplastic syndromes (MDS) represent a broad spectrum of diseases characterized by their clinical manifestation as one or more cytopenias, or a reduction in circulating blood cells. MDS is predominantly a disease of the elderly, with a median age in the UK of around 75. Approximately one third of MDS patients will develop secondary acute myeloid leukemia (sAML) that has a very poor prognosis. Unfortunately, most standard cytotoxic agents are often too toxic for older patients. This means there is a pressing unmet need for novel therapies that have fewer side effects to assist this vulnerable group. This challenge was tackled using bioinformatic analysis of available transcriptomic data to establish a gene-based signature of the development and progression of MDS. This signature was then used to identify novel therapeutic compounds via statistically-significant connectivity mapping. This approach suggested re-purposing an existing and widely-prescribed drug, bromocriptine as a novel potential therapy in these disease settings. This drug has shown selectivity for leukemic cells as well as synergy with current therapies.

  18. Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients.

    Directory of Open Access Journals (Sweden)

    Eiichiro Nagata

    Full Text Available Bromocriptine mesylate (BRC, a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS Here we report a first in human trial in ALS.A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial.The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7. The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1st endpoint and upon completion or discontinuation of the study (2nd endpoint of the dosing.Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1st and 2nd endpoint analysis. In the 1st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%, eating and drinking (P = 2.2%, ALSFRS-R total (P = 17.6%, grip strength (P = 19.8% compared to the placebo group. In the 2nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%, ALSAQ40-communication (P = 11.9%, eating and drinking (P = 13.6%, and neck forward-bent test (P = 15.4% of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence.BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment.UMIN Clinical Trials UMIN000008527.

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

    Chamarthi, Bindu; Cincotta, Anthony H


    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 QR therapy resulted in % HbA1c reductions of -0.95 and -1.49 relative to baseline (p 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: Identifier: NCT00377676.

  20. Effect of repeated L-DOPA, bromocriptine, or lisuride administration on preproenkephalin-A and preproenkephalin-B mRNA levels in the striatum of the 6-hydroxydopamine-lesioned rat. (United States)

    Henry, B; Crossman, A R; Brotchie, J M


    Abnormal involuntary movements, or dyskinesias, plague current symptomatic approaches to the treatment of Parkinson's disease. The neural mechanisms underlying the generation of dyskinesia following repeated l-3,4-dihydroxyphenylalanine (L-DOPA) or dopamine agonist administration in Parkinson's disease remain unknown. However, de novo administration of bromocriptine or lisuride to either l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primates or patients can alleviate parkinsonian symptoms without the development of dyskinesia. In this study, we have investigated behavioral responses and alterations in the expression of opioid neuropeptide precursors preproenkephalin-A (PPE-A, encoding methionine- and leucine-enkephalin) and preproenkephalin-B (PPE-B), the precursor encoding dynorphins (dynorphin A1-17 and B1-13, leucine-enkephalin, and alpha-neoendorphin) in striatal output pathways of the 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease. Expression was assessed following repeated L-DOPA, bromocriptine, or lisuride administration. Given the functional organization of basal ganglia circuitry into anatomically discrete parallel circuits, we investigated alterations in peptide expression with reference to the detailed topography of the striatum. Following repeated L-DOPA administration (6.5 mg/kg, b.d., 21 days) in the 6-OHDA-lesioned rat a rotational response was observed. This became markedly enhanced with repeated treatment. We have previously characterized the pharmacology of this enhanced response and have suggested that it is a useful model for the elucidation of the cellular and molecular mechanisms underlying L-DOPA- and dopamine agonist-induced dyskinesia. In contrast to l-DOPA, de novo administration of bromocriptine (1 or 5 mg/kg, b.d., 21 days) or lisuride (0.01 or 0.1 mg/kg, b.d., 21 days) did not lead to an enhanced behavioral response. In vehicle-treated, 6-OHDA-lesioned animals, PPE-A expression was elevated rostrally and

  1. X-ray crystal structure and conformational analysis of N-(3-dimethylaminopropyl)-N-(ethylaminocarbonyl)-6-(2-propenyl)er goline -8 beta-carboxamide (Cabergoline): comparison with bromocriptine and lisuride and a hypothesis for its high dopaminergic activity. (United States)

    Sabatino, P; Riva di Sanseverino, L; Tonani, R


    The crystal structure of Cabergoline, a potent and long lasting prolactin lowering agent interacting with the D2 dopamine receptors, has been determined by X-ray diffraction data. The structural data represent the starting point for a computational study, where the molecular mechanisms approach was used to explore the motion of all unconstrained torsion angles. Two different conformations related to energetic minima have been found, one of them in agreement with the experimental crystal structure. Both conformations are shape compared with Bromocriptine and Lisuride, two dopaminergic ergoline derivatives with C-8 beta and C-8 alpha substituents of the ergoline ring, respectively. We observe that the C-8 beta Cabergoline assumes the overall three-dimensional features of C-8-alpha-ergolines in one of its low-energy conformations.

  2. Cabergoline or bromocriptine for prolactinoma?


    Nicolás Triantafilo; Victoria Castro-Gutiérrez; Gabriel Rada


    Resumen Cabergolina y bromocriptina son los fármacos más utilizados en el manejo del prolactinoma. Si bien cabergolina, un agonista dopaminérgico de vida media larga, tendría algunas ventajas desde el punto de vista fisiopatológico, no está claro si esto se traduce en un real beneficio. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos dos revisiones sistemáticas que en conjunto comprenden 12 estudios relevantes para la p...

  3. Cabergoline or bromocriptine for prolactinoma?

    Directory of Open Access Journals (Sweden)

    Nicolás Triantafilo


    Full Text Available Resumen Cabergolina y bromocriptina son los fármacos más utilizados en el manejo del prolactinoma. Si bien cabergolina, un agonista dopaminérgico de vida media larga, tendría algunas ventajas desde el punto de vista fisiopatológico, no está claro si esto se traduce en un real beneficio. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos dos revisiones sistemáticas que en conjunto comprenden 12 estudios relevantes para la pregunta, incluyendo cinco estudios controlados aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que la cabergolina es superior a la bromocriptina en la mejoría de la oligomenorrea/amenorrea y la galactorrea, probablemente aumenta la probabilidad de embarazo, y se asocia a menos efectos adversos. No está claro si cabergolina también es más efectiva sobre el crecimiento del tumor porque la certeza de la evidencia es muy baja.

  4. Low intensity laser therapy is comparable to bromocriptine-evening ...

    African Journals Online (AJOL)

    blind study was applied on 80 patients with cyclical mastalgia. They were randomly divided into two groups (A and B) ... Evaluation oftreatment was both subjective (using VAS) and objective (studying the ... but in the latter, it acted on a wider sector of patients. In conclusion, LILT is recommended as a new treatment modality.

  5. Novel therapies for the management of type 2 diabetes mellitus: part 1. pramlintide and bromocriptine-QR. (United States)

    Grunberger, George


    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.

  6. Effects of bromocriptine mesylate on homocysteine and high-sensitivity C-reactive protein levels in patients with type-2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Mitra Niafar


    Results: In 64 patients (46 completed 6 months of treatment, age was 55±7 years and the duration of T2DM was 8.0±4.4 years. On enrollment, mean HbA1c, FPG, hs-CRP and HOMC levels were 9.0±1.3 percent, 184±42 mg/dL, 3.8±3.4 mg/dl and 10.8±6.2 micromole/L; respectively. Mean decrease of 0.7±1.1 percent for HbA1c (P=0.001 and 22±44 mg/dL for FPG was observed (P=0.002. HOMC levels decreased to 8.5±5.2 micromole/L (P=0.011 while hs-CRP levels remained unchanged at 3.7±2.9 mg/dL (P=0.835. Conclusion: While HOMC and HbA1c levels decreased significantly after 6 months of treatment with BROM-QR in patients with T2DM, serum levels of hs-CRP, total cholesterol and triglyceride did not significantly change.

  7. Hyperprolactinemia Diagnosis and Treatment (United States)

    ... tumor size. The drug most often used is cabergoline, but bromocriptine is another option. Both medications work ... drug is available, your doctor may give you cabergoline or bromocriptine to lower prolactin production. Or, if ...

  8. Establishing the dopamine dependency of human striatal signals during reward and punishment reversal learning

    National Research Council Canada - National Science Library

    Schaaf, M.E. van der; Schouwenburg, M.R. van; Geurts, D.E.M; Schellekens, A.F.A; Buitelaar, J.K; Verkes, R.J; Cools, R


    ..., during reward and punishment learning in humans, by adopting a coadministration design. Participants (N = 22) were scanned on 4 occasions using functional magnetic resonance imaging, following intake of placebo, bromocriptine...

  9. Adénome à prolactine induit par les antipsychotiques

    National Research Council Canada - National Science Library

    Marrag Ilyes; Hajji Kilani


    ... la prescription de la Bromocriptine (Parlodel®) avec augmentation progressive de la posologie et monitorage du taux plasmatique de la prolactine dans trois mois ainsi qu'une surveillance des effets psychiatrique vue le risque...

  10. Dopamine: the forgotten felon in type 2 diabetes. (United States)

    Kalra, Sanjay; Kalra, Bharti; Agrawal, Navneet; Kumar, Satish


    This paper reviews recent patents and development related to bromocriptine and other dopaminergic agents, being used or suggested for use in the management of diabetes. The article discusses the contribution of dopaminergic pathways to glucose, energy and weight homeostasis. The mechanism of action of bromocriptine, its pharmacological properties, efficacy, safety and tolerability are assessed. The article also covers recent patents which may be utilized to improve the efficiency and tolerability of dopamine-based therapy in diabetes mellitus.

  11. Cabergoline therapy for Macroprolactinoma during pregnancy: A case report


    Shahzad Hira; Sheikh Aisha; Sheikh Lumaan


    Abstract Background We assessed the safety of Cabergoline therapy during pregnancy in a lady with hyperprolactinemia intolerant to Bromocriptine. Case presentation We report the case of a 31 year old lady who presented to us with uncontrolled hyperprolactinemia. A pituitary Macroadenoma was demonstrated by MRI. Due to intolerance to Bromocriptine, Cabergoline was started. The patient improved and subsequently conceived. MRI in the second trimester demonstrated further reduction in the tumor s...

  12. Lisuride in the treatment of Parkinsonism. (United States)

    Schachter, M; Sheehy, M P; Parkes, J D; Marsden, C D


    Lisuride 1.2-4.8 mg daily was given to 10 patients with severe Parkinsonism for up to 9 months. All had been taking bromocriptine and eight had been taking levodopa combined with carbidopa. Total replacement of bromocriptine by lisuride was achieved in every case, but partial or total levodopa replacement was possible only in five patients. Lisuride 1 mg has approximately the same antiparkinsonian activity as bromocriptine 15 mg or levodopa 250-500 mg combined with carbidopa, but the duration of action of each dose is short, and gastro-intestinal and neuropsychiatric side effects are common. However, lisuride i.v. may be of considerable value in the emergency treatment of severe Parkinsonism.

  13. The use of lisuride, a potent dopamine and serotonin agonist, in the treatment of progressive supranuclear palsy.


    Neophytides, A; Lieberman, A N; Goldstein, M; Gopinathan, G; Leibowitz, M; Bock, J; Walker, R


    Seven patients with progressive supranuclear palsy were treated with lisuride. Mean age was 62 years (range, 52 to 68 years), and duration of disease was 4.4 years (range, 1 to 7 years). All seven had been treated with levodopa/carbidopa and three with bromocriptine; four had, at one time, shown a partial response to levodopa. One patient had also shown a partial response to bromocriptine. Lisuride was used alone in four patients, and combined with levodopa/carbidopa in three patients. Mean d...

  14. [Inhibition of prolactin secretion and androgenic function in the adult male rat]. (United States)

    Jarrige, J F; André, M; Grizard, G; Boucher, D


    The effects of bromocriptine induced hypoprolactinemia on the testicular function were studied in adult rats. Bromocriptine treatment (1500 micrograms/day for 24 days) reduced serum and pituitary Prolactin levels, indicating a decrease in prolactin secretion and synthesis. No change in reproductive organ weights was seen in treated animals. Hypoprolactinemia had no effect on plasma testosterone or androstenedione levels and testicular androstenedione content, but decreased significantly testicular testosterone content. These findings indicated that experimental hypoprolactinemia induced a decrease in testicular testosterone content without affecting androgens levels.

  15. Porcine stress syndrome: an animal model for the neuroleptic malignant syndrome? (United States)

    Keck, P E; Seeler, D C; Pope, H G; McElroy, S L


    The porcine stress syndrome is a genetic disorder of swine which, like neuroleptic malignant syndrome, is characterized by hyperthermia, muscle rigidity, and autonomic dysfunction. We investigated the porcine stress syndrome as a possible animal model for neuroleptic malignant syndrome in two ways. First, we administered haloperidol and lithium carbonate, alone and in combination, to susceptible and resistant swine. Second, we attempted to prevent the syndrome by pretreating animals with bromocriptine. Porcine stress syndrome was induced in 2 of 3 susceptible and 1 of 3 resistant swine by combined treatment with lithium and haloperidol, but was not triggered by treatment with lithium or haloperidol alone. Pretreatment with bromocriptine conferred no protection against the syndrome.

  16. Vanishing tumor in pregnancy

    Directory of Open Access Journals (Sweden)

    M V Vimal


    Full Text Available 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.

  17. A Review of Neuro-ophthalmologic Emergencies

    African Journals Online (AJOL)

    Alasia Datonye

    hyperemesis gravidarium, gastric resection, and AIDS . Thiamine is a cofactor for several essential enzymes in the. Kreb's cycle and pentose phosphate pathway. ... blood flow (as in hypotension and valsava maneuvers),stimulation of the gland in increased estrogen states such as pregnancy, anticoagulation, bromocriptine.

  18. contribution of growth hormone-releasing hormone and ...

    African Journals Online (AJOL)

    Side-effects. On occasion bolus IV doses of GHRH caused flushing and warmth of the face, transient tachycardia and a slight lowering of blood pressure. The administration of bromocriptine and atenolol in combination caused dizziness after the test in 2 elderly subjects, presumably due to hypotension. 0 adverse effects ...

  19. Anti-hyperprolactinemic effect of Ficus pumila Linn extract in rats

    African Journals Online (AJOL)

    Hair loss and hyperprolactinemia in women. Dermato-Endocrinol 2012; 4: 73. 5. Yu-lee LY, Luo GY, Book ML. Lactogenic hormone signal transduction. Biol Reprod 1998; 58: 295-301. 6. Webster J, Piscitell G, Polli A. A Comparison of. Cabergoline and Bromocriptine in the Treatment of. Hyperprolactinemic Amenorrhea.

  20. Case report

    African Journals Online (AJOL)


    Investigations revealed an elevated fasting blood sugar and an elevated prolactin and growth hormone level. A CT scan and MRI done showed a hemorrhagic pituitary macroadenoma. She was put on bromocriptine, ocreotide, analgesics and insulin. Thereafter, she underwent transphenoidal surgery, where near total ...

  1. Rapid left ventricular recovery after cabergoline treatment in a patient with peripartum cardiomyopathy

    NARCIS (Netherlands)

    de Jong, Jonas S. S. G.; Rietveld, Kirsten; van Lochem, Laura T.; Bouma, Berto J.


    The aetiology of peripartum cardiomyopathy (PPCM) is still largely unknown. Recent evidence suggests that the breakdown products from prolactin can induce cardiomyopathy. Prolactin secretion can be reduced with bromocriptine which had beneficial effects in a small study. We present a case of a

  2. Cerebrospinal fluid leakage as complication of treatment with cabergoline for macroprolactinomas.

    NARCIS (Netherlands)

    Netea-Maier, R.T.; Lindert, E.J. van; Timmers, H.J.L.M.; Schakenraad, E.L.; Grotenhuis, J.A.; Hermus, A.R.M.M.


    Treatment of patients with prolactinomas consists primarily of dopamine agonists (DA). Cerebrospinal fluid (CSF) leakage has sporadically been reported in patients with macroprolactinomas treated with short-acting DA such as bromocriptine. Little is known on the incidence of this complication in

  3. Massive reduction of tumour load and normalisation of hyperprolactinaemia after high dose cabergoline in metastasised prolactinoma causing thoracic syringomyelia.

    NARCIS (Netherlands)

    Uum, S.H.M. van; Alfen, N. van; Wesseling, P.; Lindert, E.J. van; Pieters, G.F.F.M.; Nooijen, P.T.G.A.; Hermus, A.R.M.M.


    In 1970 a 20 year old woman presented with a pituitary chromophobe adenoma for which she underwent transfrontal pituitary surgery. In 1978 she had to be reoperated on because of local tumour recurrence, resulting in hypopituitarism. Bromocriptine (5 mg/day) was given for 15 years, but the plasma

  4. Anorectic effect of lisuride and other ergot derivatives in the rat. (United States)

    Carruba, M O; Ricciardi, S; Müller, E E; Mantegazza, P


    Three ergot derivatives, lisuride, lergotrile and bromocriptine, given to rats trained to eat 4 h a day, induced a dose- and time-related anorexia. They were more potent in this context than either amphetamine or fenfluramine. Lisuride and lergotrile failed to increase locomotor activity or to induce stereotyped behaviour at doses corresponding to the ID50 on food intake. At this dose, bromocriptine slightly stimulated motor activity. The anorectic effect of the three compounds was selectively antagonized by blockers of dopamine (DA) receptors in the central nervous system but not by either inhibiton of catecholamine synthesis or blockade of alpha- or beta-adrenoceptors or of serotonergic receptors. Also two blockers of 'peripheral' DA receptors failed to antagonize ergoline-induced anorexia. These findings indicate that stimulation of DA receptors involved in feeding behaviour was responsible for the anorexigenic effect of the ergot derivatives investigated. In most instances this effect occurred at dose levels which failed to induce central stimulant effects.

  5. Effects of Various Drugs on Alcohol-induced Oxidative Stress in the Liver

    Directory of Open Access Journals (Sweden)

    Svetlana Trivic


    Full Text Available The major aim of this work was to investigate how alcohol-induced oxidative stress in combined chemotherapy changes the metabolic function of the liver in experimental animals. This research was conducted to establish how bromocriptine, haloperidol and azithromycin, applied to the experimental model, affected the antioxidative status of the liver. The following parameters were determined: reduced glutathione, activities of glutathione peroxidase, glutathione reductase, peroxidase, catalase, xanthine oxidase and lipid peroxidation intensity. Alanine transaminase was measured in serum. Alcohol stress (AO group reduced glutathione and the activity of xanthine oxidase and glutathione peroxidase, but increased catalase and alanine transaminase activity. The best protective effect was achieved with the bromocriptine (AB1 group, while other groups had similar effects on the studied parameters.

  6. Pulmonary Artery Occlusion and Mediastinal Fibrosis in a Patient on Dopamine Agonist Treatment for Hyperprolactinemia

    DEFF Research Database (Denmark)

    Su, Junjing; Simonsen, Ulf; Carlsen, Jørn


    Unusual forms of pulmonary hypertension include pulmonary hypertension related to mediastinal fibrosis and the use of serotonergic drugs. Here, we describe a patient with diffuse mediastinal fibrosis and pulmonary hypertension while she was on dopamine agonist therapy. A young woman, who...... showed fibrosis and chronic inflammation. Subsequent investigations revealed that diffuse mediastinal fibrosis with concurrent pulmonary hypertension, and not CTEPH, was the most likely diagnosis and cabergoline and bromocriptine may have triggered the fibrotic changes. Both drugs are ergot...... was treated with cabergoline and bromocriptine for hyperprolactinemia, presented with progressive dyspnea over several months. Based on the clinical investigation results, in particular, elevated pulmonary arterial pressures and significant perfusion defects on computed tomography (CT) pulmonary angiography...

  7. Cabergoline therapy for Macroprolactinoma during pregnancy: A case report

    Directory of Open Access Journals (Sweden)

    Shahzad Hira


    Full Text Available Abstract Background We assessed the safety of Cabergoline therapy during pregnancy in a lady with hyperprolactinemia intolerant to Bromocriptine. Case presentation We report the case of a 31 year old lady who presented to us with uncontrolled hyperprolactinemia. A pituitary Macroadenoma was demonstrated by MRI. Due to intolerance to Bromocriptine, Cabergoline was started. The patient improved and subsequently conceived. MRI in the second trimester demonstrated further reduction in the tumor size. It was decided to continue Cabergoline throughout pregnancy to ensure further reduction in tumor size until delivery and to hold Cabergoline during postpartum period to allow for an adequate interval of breastfeeding. At 37 weeks of gestation, the patient delivered a healthy baby. Conclusion We were able to safely treat macroprolactinemia in our patient during pregnancy with cabergoline. This case report contributes to the relatively meager data available which advocates the safety of cabergoline therapy in pregnant hyperprolactinemic patients.

  8. Cabergoline therapy for macroprolactinoma during pregnancy: a case report. (United States)

    Shahzad, Hira; Sheikh, Aisha; Sheikh, Lumaan


    We assessed the safety of Cabergoline therapy during pregnancy in a lady with hyperprolactinemia intolerant to Bromocriptine. We report the case of a 31 year old lady who presented to us with uncontrolled hyperprolactinemia. A pituitary Macroadenoma was demonstrated by MRI. Due to intolerance to Bromocriptine, Cabergoline was started. The patient improved and subsequently conceived. MRI in the second trimester demonstrated further reduction in the tumor size. It was decided to continue Cabergoline throughout pregnancy to ensure further reduction in tumor size until delivery and to hold Cabergoline during postpartum period to allow for an adequate interval of breastfeeding. At 37 weeks of gestation, the patient delivered a healthy baby. We were able to safely treat macroprolactinemia in our patient during pregnancy with cabergoline. This case report contributes to the relatively meager data available which advocates the safety of cabergoline therapy in pregnant hyperprolactinemic patients.

  9. Lisuride hydrogen maleate: an ergoline with beta-adrenergic antagonist activity. (United States)

    Cote, T; Munemura, M; Kebabian, J


    Lisuride hydrogen maleate is identified as a potent beta-adrenergic antagonist using a hormone-sensitive adenylate cyclase system and [3H]dihydroalprenolol binding in cell free homogenates of rabbit cerebellum. Lisuride and two other ergolines, lergotrile and bromocriptine, and the phenothiazine, fluphenazine, all interact with spiroperidol binding sites (dopamine receptors) in the anterior pituitary; however, among these compounds lisuride is unique in its ability to antagonize the beta-adrenoceptor.

  10. Dopaminergic therapy in aphasia



    Background The dopaminergic system is involved in a wide range of cognitive functions including motor control, reward, memory, attention, problem-solving and learning. This has stimulated interest in investigating the potential of dopaminergic drugs as cognitive enhancers in aphasic patients. Aim To discuss the evidence for the use of dopaminergic agents in patients with aphasia. Levodopa (L-dopa) and the dopamine agonist bromocriptine are the two drugs that have been trialled to date. We dis...

  11. Individualized high-dose cabergoline therapy for hyperprolactinemic infertility in women with micro- and macroprolactinomas. (United States)

    Ono, Masami; Miki, Nobuhiro; Amano, Kosaku; Kawamata, Takakazu; Seki, Toshiro; Makino, Rena; Takano, Kazue; Izumi, Shun-ichiro; Okada, Yoshikazu; Hori, Tomokatsu


    Cabergoline is effective for hyperprolactinemic hypogonadism. However, the rate of cabergoline-induced pregnancy in women with prolactinoma remains unknown. Also unknown is whether cabergoline can control tumor growth and thereby achieve successful pregnancy in patients with macroprolactinomas. Eighty-five women with macroprolactinomas (n = 29) or microprolactinomas (n = 56) received prospective, high-dose cabergoline therapy for infertility based on individual prolactin suppression and/or tumor shrinkage. The patients included 31 bromocriptine-resistant, 32 bromocriptine-intolerant, and 22 previously untreated women. Conception was withheld until three regular cycles returned in women with microadenoma and until tumors shrank below 1.0 cm in height in women with macroadenoma. Cabergoline was withdrawn at the fourth gestational week. Cabergoline normalized hyperprolactinemia and recovered the ovulatory cycle in all patients. All adenomas contracted, and 11 macroadenomas and 29 microadenomas disappeared. Eighty patients (94%) conceived 95 pregnancies, two of which were cabergoline-free second pregnancies. The dose of cabergoline at the first pregnancy was 0.25-9 mg/wk overall and 2-9 mg/wk in the resistant patients. Of the 93 pregnancies achieved on cabergoline, 86 resulted in 83 single live births, one stillbirth, and two abortions; the remaining seven were ongoing. All babies were born healthy, without any malformations. No mothers experienced impaired vision or headache suggestive of abnormal tumor reexpansion throughout pregnancy. Cabergoline achieved a high pregnancy rate with uneventful outcomes in infertile women with prolactinoma, independent of tumor size and bromocriptine resistance or intolerance. Cabergoline monotherapy could substitute for the conventional combination therapy of pregestational surgery or irradiation plus bromocriptine in macroprolactinomas.

  12. The Medical Treatment of New-Onset Peripartum Cardiomyopathy: A Systematic Review of Prospective Studies. (United States)

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


    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.

  13. Studies on sensitivity of zebrafish as a model organism for Parkinson's disease: Comparison with rat model (United States)

    Makhija, Dinesh T.; Jagtap, Aarti G.


    Objective: To determine the utility of zebra fish as an animal model for Parkinson's disease (PD) in comparison with rat model. Materials and Methods: MTT assay was performed on rat and zebrafish brain synaptosomal fractions using rotenone as a neurotoxic agent. Quercetin and resveratrol were used as standards to compare anti-apoptotic activity in both organisms. Catalepsy was induced in zebrafish by exposing them to haloperidol (9 μM) solution. Drug-treated groups were exposed to bromocriptine and pramipexole, 30 min prior to haloperidol exposure at the dose of 2, 5, and 10 μg/mL. Swimming speed, time spent in the bottom of the tank, and complete cataleptic time were evaluated to assess behavioral changes. In rats, catalepsy was induced using haloperidol (1.25 mg/kg i.p.). Drug-treated groups received bromocriptine (2.5 mg/kg.) and pramipexole (1 mg/kg) orally. Bar test, block test, and locomotor activity were carried out to assess behavioral changes. Results: Resveratrol and quercetin showed comparable inhibition of apoptosis in rats and zebrafish. In anti-cataleptic study, bromocriptine and pramipexole-treated groups showed significant difference (P behavioral parameters as compared to haloperidol control group in both the experimental organisms. Results obtained from fish model were in correlation with rat model. Conclusion: Findings of the present study revealed that zebrafish model is highly sensitive and can be used for basic screening of drugs against PD. PMID:24554909

  14. Managing Prolactinomas During Pregnancy: Mini Review

    Directory of Open Access Journals (Sweden)

    Mussa eAlmalki


    Full Text Available Prolactinomas are the most prevalent functional benign pituitary tumors due to a pituitary micro- or macroadenoma. The majority of patients presents with infertility and gonadal dysfunction.A dopamine agonist (DAs (bromocriptine or cabergoline is the treatment of choice that can normalize prolactin levels, reduce tumor size and restore ovulation and fertility. Cabergoline generally preferred over bromocriptine because of its higher efficacy and tolerability. Managing prolactinomas during pregnancy may be challenging. During pregnancy, the pituitary gland undergoes global hyperplasia due to a progressive increase in serum estrogens level that may lead to increase of the tumor volume with potential mass effect and visual loss.The risk of tumor enlargement may occur in 3 % of those with microadenomas, 32 % in those with macroadenomas that were not previously operated on and 4.8% of those with macroadenomas with prior ablative treatment. Though both drugs appear to be safe during pregnancy, the data on fetal exposure to DAs during pregnancy have been reported with bromocriptine far exceeds that of cabergoline with no association of increased risk of pregnancy loss and premature delivery. It is advisable to stop the use of DAs immediately once pregnancy is confirmed, except in the case of women with invasive macroprolactinomas or pressure symptoms. This review outlines the therapeutic approach to, prolactinoma during pregnancy, with emphasis on the safety of available DA therapy.

  15. Cabergoline-induced fibrosis of prolactinomas: a neurosurgical perspective. (United States)

    Mohan, Niraj; Chia, Yi Yan; Goh, Giap Hean; Ting, Eric; Teo, Kejia; Yeo, Tseng Tsai


    Presently, the standard of care for prolactinomas, a type of pituitary adenoma, is dopaminergic agents such as bromocriptine and cabergoline. However, dopaminergic agents may induce fibrosis of cardiac valves leading to valvular insufficiency, necessitating surgical treatment of prolactinoma. Fibrosis of prolactinoma can be induced by prolonged medical treatment with bromocriptine, and this usually occurs after years of treatment. In comparison to bromocriptine, there have been no reports of cabergoline-induced fibrosis of prolactinoma. There is a potential for greater emphasis to be placed on assessing the tumour consistency from preoperative MRI scans, or even preoperative contrast-enhanced 3D Fast Imaging Employing Steady-state Acquisition imaging to allow better planning of the surgery. We report a rare case of fibrosis of prolactinoma after cabergoline treatment resulting in its subsequent difficult surgical removal. This patient had early MRI changes of fibrosis of prolactinoma after a short period of 6 months of cabergoline treatment. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Resolution of multiple substrate binding sites in cytochrome P450 3A4: the stoichiometry of the enzyme-substrate complexes probed by FRET and Job’s titration† (United States)

    Fernando, Harshica; Halpert, James R.; Davydov, Dmitri R.


    To explore the mechanism of homotropic cooperativity in human cytochrome P450 3A4 (CYP3A4) we studied the interactions of the enzyme with 1-pyrenebutanol (1-PB), 1- pyrenemethylamine (PMA), and bromocriptine by FRET from the substrate fluorophore to the heme, and by absorbance spectroscopy. These approaches combined with an innovative setup of titration-by-dilution and continous variation (Job’s titration) experiments allowed us to probe the relationship between substrate binding and the subsequent spin transition caused by 1-PB or bromocriptine or the Type-II spectral changes caused by PMA. The 1-PB-induced spin shift in CYP3A4 reveals prominent homotropic cooperativity, which is characterized by a Hill coefficient of 1.8 ± 0.3 (S50 = 8.0 ± 1.1 µM). In contrast, the interactions of CYP3A4 with bromocriptine or PMA reveal no cooperativity, exhibiting KD values of 0.31 ± 0.08 µM and 6.7 ± 1.9 µM, respectively. The binding of all three substrates monitored by FRET in titration-by-dilution experiments at an enzyme:substrate ratio of 1 reveals a simple bimolecular interaction with KD values of 0.16 ± 0.09, 4.8 ± 1.4, and 0.18 ± 0.09 µM for 1-PB, PMA, and bromocriptine respectively. Correspondingly, the Job’s titration experiments showed that the 1-PB-induced spin shift reflects the formation of a complex of the enzyme with two substrate molecules, while bromocriptine and PMA exhibit 1:1 binding stoichiometry. Combining the results of Job’s titrations with the value of KD obtained in our FRET experiments, we demonstrate that the interactions of CYP3A4 with 1-PB obey a sequential binding mechanism, where the spin transition is triggered by the binding of 1-PB to the low-affinity site, which becomes possible only upon saturation of the high-affinity site. PMID:16566594

  17. Decreasing prolactin levels leads to a lower diving effort but does not affect breeding success in Adélie penguins. (United States)

    Cottin, Manuelle; Chastel, Olivier; Kato, Akiko; Debin, Marion; Takahashi, Akinori; Ropert-Coudert, Yan; Raclot, Thierry


    Current research on seabirds suggests a key role of hormones in the trade-off between self-maintenance and parental investment through their influence on foraging decisions during the breeding period. Although prolactin is known to have major effects on parental care, its role in foraging behavior has rarely been investigated in seabirds to date. The aim of this study was to assess the influence of an experimental decrease in prolactin levels on foraging decisions and its consequences on breeding success in free-living seabirds. To achieve this, we implanted bromocriptine (an inhibitor of prolactin secretion) in male Adélie penguins (Pygoscelis adeliae), monitored their foraging behavior using time-depth recorders over several trips, and recorded their reproductive output. On average 8±0.5days after implantation, we showed that bromocriptine administration led to an efficient decrease in prolactin levels. However, no differences were seen in foraging trip durations between bromocriptine-implanted birds and controls. Moreover, the time spent diving and the number of dives performed per trip were similar in both groups. By contrast, all diving parameters (including diving efficiency) were negatively affected by the treatment during the first at-sea trip following the treatment. Finally, the treatment did not affect adult body condition or chick growth and survival. Our study highlights the short-term negative effect of low prolactin levels on diving effort, but indicates that a short-term and/or low-magnitude decrease in prolactin levels alone is not sufficient to modify consistently the body maintenance or the parental investment of Adélie penguins. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. [Severe pulmonary embolism and acute lower limb ischemia complicating peripartum cardiomyopathy successfully treated by streptokinase]. (United States)

    Yaméogo, N V; Kaboré, E; Seghda, A; Kagambèga, L J; Kaboré, H P; Millogo, G R C; Kologo, K J; Kambiré, Y; Bama, A; Toguyeni, B J Y; Samadoulougou, A K; Zabsonré, P


    Peripartum cardiomyopathy is a cardiac disease at high thromboembolism potential. The authors report a case of peripartum cardiomyopathy admitted for congestive heart failure. Echocardiography found a dilated cardiomyopathy with severely impaired left ventricular systolic function and biventricular thrombi. During hospitalization his condition was complicated by severe bilateral pulmonary embolism and left lower limb arterial acute thrombosis. The treatment consisted of thrombolysis with streptokinase associated with dobutamine (in addition to the conventional treatment of heart failure and bromocriptine). The outcome was favorable, marked by pulmonary and lower limb arterial unblocking. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  19. Neuroleptic Malignant Syndrome: A Case Aimed at Raising Clinical Awareness

    Directory of Open Access Journals (Sweden)

    Jad Al Danaf


    Full Text Available A 60-year-old man with a history of bipolar disorder on risperidone, bupropion, and escitalopram was admitted for community acquired streptococcal pneumonia. Four days later, he developed persistent hyperthermia, dysautonomia, rigidity, hyporeflexia, and marked elevation of serum creatine phosphokinase. He was diagnosed with neuroleptic malignant syndrome (NMS and improved with dantrolene, bromocriptine, and supportive therapy. This case emphasizes the importance of considering a broad differential diagnosis for fever in the ICU, carefully reviewing the medication list for all patients, and considering NMS in patients with fever and rigidity.

  20. The Relationship between Statins and Prostate Cancer Prevention (United States)


    outside entities 2003 Resident’s Perspective on Professionalism; Presenter New Orleans, LA (Accreditation Council for Graduate Medical Education...Quick release bromocriptine (Cycloset ™) improves glycaemic control in patients with diabetes failing metformin /sulfonylurea combination therapy...hi st or y (y es o r no ), ag e (y ea rs ), se ru m t ot al c ho le st er ol (m g/ dL ), ra ce (w hi te , b la ck , o th er , o r m is

  1. Acromegaly due to GHRH-secreting large bronchial carcinoid. Complete recovery following tumor surgery. (United States)

    Bolanowski, M; Schopohl, J; Marciniak, M; Rzeszutko, M; Zatonska, K; Daroszewski, J; Milewicz, A; Malczewska, J; Badowski, R


    A case of acromegaly, secondary to GHRH secretion by a large bronchial carcinoid is reported. A 61-year-old woman presented with typical symptoms and signs of acromegaly for at least 10 years. She suffered from recurrent pneumonias, but repeated chest X-ray examinations failed to demonstrate the bronchial tumor. The diagnosis was confirmed by elevated GH, IGF-1 and GHRH secretion. We have shown an enlarged pituitary gland without focal lesions together with a cerebral meningioma on MRI and the presence of a bronchial carcinoid tumor. The latter was confirmed by histology carried out after bronchoscopy and tumor excision. We observed partial suppression of GH secretion following short-term oral bromocriptine administration in this patient. Surgical removal of the carcinoid tumor resulted in a complete clinical, hormonal and radiological cure of acromegaly. This case of acromegaly due to ectopic GHRH secretion by bronchial carcinoid differs from others described in the literature by an atypical large tumor size, the suppression of elevated GH secretion by oral bromocriptine and a concomitant meningioma.

  2. The use of lisuride, a potent dopamine and serotonin agonist, in the treatment of progressive supranuclear palsy. (United States)

    Neophytides, A; Lieberman, A N; Goldstein, M; Gopinathan, G; Leibowitz, M; Bock, J; Walker, R


    Seven patients with progressive supranuclear palsy were treated with lisuride. Mean age was 62 years (range, 52 to 68 years), and duration of disease was 4.4 years (range, 1 to 7 years). All seven had been treated with levodopa/carbidopa and three with bromocriptine; four had, at one time, shown a partial response to levodopa. One patient had also shown a partial response to bromocriptine. Lisuride was used alone in four patients, and combined with levodopa/carbidopa in three patients. Mean dose of lisuride was 2.5 mg (range, 1.5 to 5.0 mg). Mean duration of treatment was 4 months (range, 1 to 10 months). While two patients showed a reduction in rigidity, one in tremor and two in bradykinesia, in only one of them was there an overall improvement. It is postulated that the relative lack of response to lisuride may be due to a loss of both the dopaminergic and serotonergic receptors in progressive supranuclear palsy.

  3. Cost-Effectiveness Analysis of Surgical versus Medical Treatment of Prolactinomas. (United States)

    Zygourakis, Corinna C; Imber, Brandon S; Chen, Rebecca; Han, Seunggu J; Blevins, Lewis; Molinaro, Annette; Kahn, James G; Aghi, Manish K


    Background Few studies address the cost of treating prolactinomas. We performed a cost-utility analysis of surgical versus medical treatment for prolactinomas. Materials and Methods We determined total hospital costs for surgically and medically treated prolactinoma patients. Decision-tree analysis was performed to determine which treatment produced the highest quality-adjusted life years (QALYs). Outcome data were derived from published studies. Results Average total costs for surgical patients were $19,224 ( ± 18,920). Average cost for the first year of bromocriptine or cabergoline treatment was $3,935 and $6,042, with $2,622 and $4,729 for each additional treatment year. For a patient diagnosed with prolactinoma at 40 years of age, surgery has the lowest lifetime cost ($40,473), followed by bromocriptine ($41,601) and cabergoline ($70,696). Surgery also appears to generate high health state utility and thus more QALYs. In sensitivity analyses, surgery appears to be a cost-effective treatment option for prolactinomas across a range of ages, medical/surgical costs, and medical/surgical response rates, except when surgical cure rates are ≤ 30%. Conclusion Our single institution analysis suggests that surgery may be a more cost-effective treatment for prolactinomas than medical management for a range of patient ages, costs, and response rates. Direct empirical comparison of QALYs for different treatment strategies is needed to confirm these findings.

  4. Secondary resistance to cabergoline therapy in a macroprolactinoma: a case report and literature review.

    LENUS (Irish Health Repository)

    Behan, L A


    Primary resistance to dopamine agonists occurs in 10-15% of prolactinomas but secondary resistance following initial biochemical and anti-proliferative response is very rare and has only been hitherto described in four previous cases, two with bromocriptine and two with cabergoline. We describe a case of a 57-year-old woman who presented with a large macroprolactinoma with suprasellar extension. She was initially treated with bromocriptine therapy with a resolution of symptoms, marked reduction in prolactin concentration and complete tumour shrinkage; a response which was subsequently maintained on cabergoline. After 8 years of dopamine agonist therapy, her prolactin concentration began to rise and there was symptomatic recurrence of her tumour despite escalating doses of cabergoline up to 6 mg weekly. Non-compliance was outruled by observed inpatient drug administration. The patient underwent surgical debulking followed by radiotherapy with good response. This case adds to the previous two cases of secondary resistance to cabergoline therapy in prolactinomas a marked initial response. While the mechanism of secondary resistance remains unknown and not possible to predict, close observation of prolactinoma patients on treatment is necessary.

  5. Managing prolactinoma during pregnancy

    Directory of Open Access Journals (Sweden)

    Maziar Azar


    Full Text Available Objective:Prolactinomas are the most common pituitary tumors in pregnant women. We conducted this study on pregnant women with prolactinoma to determine their clinical symptoms and signs and eventual necessity to medical therapy.Materials and methods:A descriptive study was performed on 85 pregnant women with prolactinoma.Patients were followed up by physical examination, imaging, and perimetry for diagnosis of visual field defect. If tumor was increased in size perimetry was performedin order to determine eventual visual field defect (VFD. Patients with progressive visual field defect had absolute indication for trans sphenoidal surgery (TSS.In other cases with progressive enlargement of adenoma size but without VFD bromocriptine was administered. Patients without increasing adenoma size were just followed up.Results:In this study 72 patients (84% had microadenomas, 7 patients (8% had macroadenomas without previous medical or surgical therapy and 6 patients (7% had macroadenomas with previous medical therapy with bromocriptine. Totally 20 patients (23 % had tumor enlargement during pregnancy and was symptomatic in 7 patients (8.2%. There was significant difference between 3 groups according to incidence of symptomatic tumor enlargement.(p<0.05Conclusion:Macroprolactinomas are more likely to enlarge during pregnancy than microprolactinomas. In our study conservative management was successfully done in all patients without surgery or medical therapy.

  6. Impulse control disorders in Chinese Parkinson's disease patients: the effect of ergot derived dopamine agonist. (United States)

    Auyeung, M; Tsoi, T H; Tang, W K; Cheung, C M; Lee, C N; Li, R; Yeung, Eric


    We studied the prevalence and related risk factors of impulse control disorders in Chinese Parkinson's disease patients. We screened all non-demented Parkinson's disease patients attending our Parkinson's disease clinic from August 2009 to March 2010. The clinical characteristics of patients with impulse control disorders and those without were compared. Of the 213 PD subjects screened, 15 (7.0%) with impulse control disorders were identified. Fourteen of these subjects were on both a dopamine agonist and Levodopa, and one was on Levodopa alone. Of the fourteen subjects on both a dopamine agonist and Levodopa, eleven were on bromocriptine and Levodopa; 10.5% of the subjects exposed to bromocriptine had impulse control disorder. Upon multivariate analysis, dose of dopamine agonist used, young age at onset of Parkinson's disease and a history of anxiety or depression were independent predictors for developing impulse control disorders. 7% of our Chinese PD subjects had impulse control disorders. When young Parkinson's disease patients with a history of anxiety or depression are treated with high dose of DA, they are at risk of developing impulse control disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. [Mammary carcinoma in a patient with hyperprolactinemia]. (United States)

    Gola, M; Papi, G; Tavernari, V; Pesenti, M; Ficarra, G; Velardo, A


    In 1990, a 50 year-old man was referred to us for hyperprolactinemia. At 37 years of age the patient had undergone left mastectomy, for a histologically confirmed gynecomastia and, in 1989, he had undergone pituitary adenomectomy, for a PRL secreting macroadenoma (PRL = 3520 ng/ml). Persistently high PRL plasma levels (PRL = 550 ng/ml) showed an incomplete surgical removal of the adenoma and as a consequence, radiotherapy of the pituitary area was performed in 1990. When the patient referred to us, PRL plasma levels were still pathologic and medical therapy with bromocriptine was started. A year later a replacement therapy with cortisone, testosterone, L-thyroxine, was commenced, as the patient presented a post-radiotherapy hypopituitarism. Since the treatment with bromocriptine was unsuccessful, the drug was replaced with cabergoline, but not even the latter was able to normalize PRL plasma levels. In 1996, a nodule of 3 cm in diameter was discovered under his right mammary areola. The nodule biopsy showed a grade II infiltrating ductal breast carcinoma positive to the estrogen and progesterone receptors analysis. A right total mastectomy was performed and the diagnosis was confirmed through histological examination. A case of gynecomastia and breast cancer in a male patient who had been exposed to high PRL plasma levels for several years is reported. In this patient, both elevated PRL plasma levels and a relative hyperestrogenic state may have contributed to originate breast cancer.

  8. Management of psychotropic-induced hyperprolactinemia. (United States)

    Marken, P A; Haykal, R F; Fisher, J N


    The effects of individual psychotropic medications on serum prolactin concentrations are described, and recommendations for dealing with adverse effects are provided. Hyperprolactinemia can result in galactorrhea, amenorrhea, irregular menses, and anovulation; in men, impotence and azoospermia, with or without lactation and gynecomastia, can occur. Antipsychotics may block dopamine receptors in the pituitary prolactin-secreting cells and prevent dopamine-induced reduction of prolactin release. The magnitude of the increase in prolactin concentration correlates with the amount of antipsychotic drug given. The treatment of choice is reduction of the antipsychotic dosage or discontinuation of therapy. If adjustments to the antipsychotic dosage fail to resolve symptoms, the dopamine agonists bromocriptine and amantadine may be tried. Antidepressants may produce elevated serum prolactin concentrations, especially with long-term administration. However, the frequency of antidepressant-induced hyperprolactinemia is much lower than that seen with antipsychotics, and serious adverse clinical effects are uncommon. Other psychotropic drugs such as lithium, valproic acid, buspirone, carbamazepine, and benzodiazepines either are only rarely associated with symptomatic hyperprolactinemia or do not produce clinically important changes in prolactin concentrations. Antipsychotic drugs are the psychotropic agents most likely to cause symptomatic hyperprolactinemia. Bromocriptine or amantadine may provide symptomatic relief if withdrawal or adjustment of the antipsychotic dosage does not eliminate the symptoms.

  9. Secondary resistance to cabergoline therapy in a macroprolactinoma: a case report and literature review. (United States)

    Behan, L A; Draman, M S; Moran, C; King, T; Crowley, R K; O'Sullivan, E P; Smith, D; Thompson, C J; Agha, A


    Primary resistance to dopamine agonists occurs in 10-15% of prolactinomas but secondary resistance following initial biochemical and anti-proliferative response is very rare and has only been hitherto described in four previous cases, two with bromocriptine and two with cabergoline. We describe a case of a 57-year-old woman who presented with a large macroprolactinoma with suprasellar extension. She was initially treated with bromocriptine therapy with a resolution of symptoms, marked reduction in prolactin concentration and complete tumour shrinkage; a response which was subsequently maintained on cabergoline. After 8 years of dopamine agonist therapy, her prolactin concentration began to rise and there was symptomatic recurrence of her tumour despite escalating doses of cabergoline up to 6 mg weekly. Non-compliance was outruled by observed inpatient drug administration. The patient underwent surgical debulking followed by radiotherapy with good response. This case adds to the previous two cases of secondary resistance to cabergoline therapy in prolactinomas a marked initial response. While the mechanism of secondary resistance remains unknown and not possible to predict, close observation of prolactinoma patients on treatment is necessary.

  10. Secondary resistance to cabergoline therapy in a macroprolactinoma: a case report and literature review.

    LENUS (Irish Health Repository)

    Behan, L A


    Primary resistance to dopamine agonists occurs in 10-15% of prolactinomas but secondary resistance following initial biochemical and anti-proliferative response is very rare and has only been hitherto described in four previous cases, two with bromocriptine and two with cabergoline. We describe a case of a 57-year-old woman who presented with a large macroprolactinoma with suprasellar extension. She was initially treated with bromocriptine therapy with a resolution of symptoms, marked reduction in prolactin concentration and complete tumour shrinkage; a response which was subsequently maintained on cabergoline. After 8 years of dopamine agonist therapy, her prolactin concentration began to rise and there was symptomatic recurrence of her tumour despite escalating doses of cabergoline up to 6 mg weekly. Non-compliance was outruled by observed inpatient drug administration. The patient underwent surgical debulking followed by radiotherapy with good response. This case adds to the previous two cases of secondary resistance to cabergoline therapy in prolactinomas a marked initial response. While the mechanism of secondary resistance remains unknown and not possible to predict, close observation of prolactinoma patients on treatment is necessary.

  11. Ropinirole and pramipexole, the new agonists. (United States)

    Hobson, D E; Pourcher, E; Martin, W R


    Ropinirole and pramipexole are non-ergoline dopamine agonists which are relatively specific for the D2 family of dopamine receptors. They have side-effect profiles linked to peripheral and central dopaminergic stimulation, amenable to tolerance through a slow titration or the addition of domperidone in sensitive patients. They do not have the uncommon but problematic ergot-related side effects of bromocriptine and pergolide. Ropinirole and pramipexole have both been shown to be efficacious when used as monotherapy in early Parkinson's disease (PD), and have been suggested as being less likely than levodopa to lead to the early development of motor fluctuations and dyskinesias in this clinical setting. They have also been shown to be useful as adjunctive therapy to levodopa in advanced PD and to have a levodopa-sparing effect in these patients. Dose equivalents amongst the available dopamine agonists is difficult to know with certainty but has been estimated as follows: 30 mg of bromocriptine, 15 mg of ropinirole, 4.5 mg of pramipexole, and 3.0 mg of pergolide.

  12. The effect of dopamine agonists: the expression of GDNF, NGF, and BDNF in cultured mouse astrocytes. (United States)

    Ohta, Kiyoe; Kuno, Sadako; Inoue, Seiji; Ikeda, Erika; Fujinami, Aya; Ohta, Mitsuhiro


    In Parkinson's disease, cell death is selectively induced in mesencephalic nigral dopaminergic neurons. At present, no disease modifying therapy or radical treatment has been found for this disease. Some dopamine agonists may have a neuroprotective action in cultured cells and animal models. In the present study, we examined stimulating effects of a non-ergoline D(2) dopamine agonist, ropinirole, on synthesis/secretion of neurotrophic factors, including NGF, BDNF, and GDNF, in cultured mouse astrocytes. These effects were compared with those of ergoline dopamine agonists, SKF-38393, a D(1) agonist, bromocriptine, D(2) agonist, and apomorphine, D(1)/D(2) agonist. Ropinirole elevated GDNF levels to 4-fold, and NGF levels to 6.3-fold, compared with the control group. Of the dopamine agonists examined, ropinirole produced and secreted more GDNF than a 1.8-fold greater amount of apomorphine, a lesser amount of bromocriptine, or a 2.8-fold greater amount of SKF-38393, which served as the control group. Copyright 2010. Published by Elsevier B.V.

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

    Marcellin, L; Chantry, A A


    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.

  14. Pulmonary Artery Occlusion and Mediastinal Fibrosis in a Patient on Dopamine Agonist Treatment for Hyperprolactinemia

    Directory of Open Access Journals (Sweden)

    Junjing Su


    Full Text Available Unusual forms of pulmonary hypertension include pulmonary hypertension related to mediastinal fibrosis and the use of serotonergic drugs. Here, we describe a patient with diffuse mediastinal fibrosis and pulmonary hypertension while she was on dopamine agonist therapy. A young woman, who was treated with cabergoline and bromocriptine for hyperprolactinemia, presented with progressive dyspnea over several months. Based on the clinical investigation results, in particular, elevated pulmonary arterial pressures and significant perfusion defects on computed tomography (CT pulmonary angiography and ventilation/perfusion (V/Q scintigraphy, chronic thromboembolic pulmonary hypertension (CTEPH was initially considered the most plausible diagnosis. However, during an attempted pulmonary endarterectomy, loose fibrous tissues were observed in the mediastinum and cryosection of the right pulmonary artery showed fibrosis and chronic inflammation. Subsequent investigations revealed that diffuse mediastinal fibrosis with concurrent pulmonary hypertension, and not CTEPH, was the most likely diagnosis and cabergoline and bromocriptine may have triggered the fibrotic changes. Both drugs are ergot-derived dopamine agonists, which are known to cause cardiac valve fibrosis and less frequently, non-cardiac fibrotic changes. The underlying mechanism is attributed to their interactions with serotonin receptors. There is much evidence that serotonin, a potent vasoconstrictor and mitogen, is involved in the pathogenesis of pulmonary hypertension. In conclusion, as CT and V/Q scintigraphy findings can occasionally be deceptive, physicians should be particularly aware of differential diagnoses in patients without obvious history of venous thromboembolism that are suspected of having chronic thromboembolic pulmonary hypertension.

  15. Methods and clinical applications of positron emission tomography in endocrinology. Methodologie et applications cliniques en endocrinologie de la tomographie a emission de positons

    Energy Technology Data Exchange (ETDEWEB)

    Landsheere, C. de; Lamotte, D. (Liege Univ. (BE))


    Positron emission tomography (PET) allows to detect in coincidence photons issued from annihilation between positrons and electrons nearby situated. Tomographic detection (plane by plane) and tomographic reconstruction will lead to the quantitation of radioactive distribution per voxel, in the organ of interest. Recent tomographs can acquire simultaneously several transaxial slices, with a high sensitivity and a spatial resolution of 3-5 mm. Commonly used positron emitters have a short half-life: 2, 10, 20 and 110 min for {sup 15}0, {sup 13}N, {sup 11}C and {sup 18}F, respectively. The use of these isotopes requires on line production of radionuclides and synthesis of selected molecules. In endocrinology, PET allows among others to study noninvasively the receptor density of hormonodependent neoplasms such as breast, uterus, prostate tumors and prolactinomas. These last tumors represent a particular entity because of several combined characteristics: high turnover rate of amino acids, high density of dopaminergic receptors and response to bromocriptine (analogue of dopamine inhibiting the secretion of prolactine) in relation to the level of receptors. Because PET permits to evaluate the density of dopaminergic receptors and the metabolism of amino acids, theoretical response of the prolactinoma to bromocriptin can be predicted, the achieved therapeutic efficacy can be estimated and the long-term follow up of tumor growth can be assessed. This example illustrates the clinical value of PET in endocrinology.

  16. Intestinal mucosal changes and upregulated calcium transporter and FGF-23 expression during lactation: Contribution of lactogenic hormone prolactin. (United States)

    Wongdee, Kannikar; Teerapornpuntakit, Jarinthorn; Sripong, Chanakarn; Longkunan, Asma; Chankamngoen, Wasutorn; Keadsai, Chutiya; Kraidith, Kamonshanok; Krishnamra, Nateetip; Charoenphandhu, Narattaphol


    As the principal lactogenic hormone, prolactin (PRL) not only induces lactogenesis but also enhances intestinal calcium absorption to supply calcium for milk production. How the intestinal epithelium res-ponses to PRL is poorly understood, but it is hypothesized to increase mucosal absorptive surface area and calcium transporter expression. Herein, lactating rats were found to have greater duodenal, jejunal and ileal villous heights as well as cecal crypt depths than age-matched nulliparous rats. Morphometric analyses in the duodenum and cecum showed that their mucosal adaptations were diminished by bromocriptine, an inhibitor of pituitary PRL release. PRL also upregulated calcium transporter expression (e.g., TRPV6 and PMCA1b) in the duodenum of lactating rats. Since excessive calcium absorption could be detrimental to lactating rats, local negative regulator of calcium absorption, e.g., fibroblast growth factor (FGF)-23, should be increased. Immunohistochemistry confirmed the upregulation of FGF-23 protein expression in the duodenal and cecal mucosae of lactating rats, consistent with the enhanced FGF-23 mRNA expression in Caco-2 cells. Bromocriptine abolished this lactation-induced FGF-23 expression. Additionally, FGF-23 could negate PRL-stimulated calcium transport across Caco-2 monolayer. In conclusion, PRL was responsible for the lactation-induced mucosal adaptations, which were associated with compensatory increase in FGF-23 expression probably to prevent calcium hyperabsorption. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Establishing the dopamine dependency of human striatal signals during reward and punishment reversal learning. (United States)

    van der Schaaf, Marieke E; van Schouwenburg, Martine R; Geurts, Dirk E M; Schellekens, Arnt F A; Buitelaar, Jan K; Verkes, Robbert Jan; Cools, Roshan


    Drugs that alter dopamine transmission have opposite effects on reward and punishment learning. These opposite effects have been suggested to depend on dopamine in the striatum. Here, we establish for the first time the neurochemical specificity of such drug effects, during reward and punishment learning in humans, by adopting a coadministration design. Participants (N = 22) were scanned on 4 occasions using functional magnetic resonance imaging, following intake of placebo, bromocriptine (dopamine-receptor agonist), sulpiride (dopamine-receptor antagonist), or a combination of both drugs. A reversal-learning task was employed, in which both unexpected rewards and punishments signaled reversals. Drug effects were stratified with baseline working memory to take into account individual variations in drug response. Sulpiride induced parallel span-dependent changes on striatal blood oxygen level-dependent (BOLD) signal during unexpected rewards and punishments. These drug effects were found to be partially dopamine-dependent, as they were blocked by coadministration with bromocriptine. In contrast, sulpiride elicited opposite effects on behavioral measures of reward and punishment learning. Moreover, sulpiride-induced increases in striatal BOLD signal during both outcomes were associated with behavioral improvement in reward versus punishment learning. These results provide a strong support for current theories, suggesting that drug effects on reward and punishment learning are mediated via striatal dopamine.

  18. Synthesis of some /sup 11/C-labelled alkaloids

    Energy Technology Data Exchange (ETDEWEB)

    Laangstroem, B.; Antoni, G.; Halldin, H.; Svaerd, H.; Bergson, G. (Univ. of Uppsala (Sweden) Inst. of Chemistry)


    Using (/sup 11/C)-methyl iodide in N-alkylation reactions in dimethylformamide (DMF), the alkaloids N-(/sup 11/C-methyl)-morphine, N-(/sup 11/C-methyl)-codeine, 6-N(methyl)-9, 10-dihydroergotamine, 6-N-(/sup 11/C-methyl)-bromocriptine and N-(/sup 11/C-methyl)-nicotine have been synthesized in radiochemical yields of 50-95%, within 5-10 min of introducing (/sup 11/C)-methyl iodide into the reaction vial. (/sup 11/C)-Methyl iodide was obtained within 4-7 min from (/sup 11/C)-carbon dioxide prepared by the /sup 14/N(p,..cap alpha..)/sup 11/C reaction.

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

    Lees, A J; Bannister, R


    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.

  20. [Treatment on fatigue of patients with postpolio syndrome. A systematic review]. (United States)

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


    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.

  1. Catatonia, neuroleptic malignant syndrome, and cotard syndrome in a 22-year-old woman: a case report. (United States)

    Weiss, C; Santander, J; Torres, R


    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.

  2. Neuroleptic Malignant Syndrome in a Patient with Tongue Cancer: A Report of a Rare Case

    Directory of Open Access Journals (Sweden)

    Osamu Baba


    Full Text Available Background. Neuroleptic malignant syndrome (NMS is a rare but life-threatening complication of neuroleptic drugs, which are used widely in head and neck cancer (HANC patients who develop delirium. Methods and Results. Postoperative delirium in a 39-year-old man with tongue cancer was treated with haloperidol and chlorpromazine. Three days after the first administration of antipsychotics, the patient exhibited elevated body temperature, autonomic and extrapyramidal symptoms, and impaired consciousness. A definitive diagnosis was made using the research diagnostic criteria for NMS in the DSM-IV, and the antipsychotics were immediately discontinued. The patient was given dantrolene and bromocriptine to treat the NMS. The patient’s hyperthermia, elevated creatinin kinase (CK, and muscle rigidity improved gradually, with all symptoms of NMS resolving completely by 13 days after the diagnosis. Conclusions. HANC surgeons must be alert for early signs of NMS and use antipsychotics conservatively to avoid NMS and its potentially fatal outcome.

  3. Ropinirole: a review of its use in the management of Parkinson's disease. (United States)

    Matheson, A J; Spencer, C M


    Ropinirole, a non-ergoline dopamine agonist, has selective affinity for dopamine D2-like receptors and little or no affinity for non-dopaminergic brain receptors. Ropinirole is indicated as adjunct therapy to levodopa in patients with advanced Parkinson's disease. It is also indicated, and recent clinical trials have focused on its use, as monotherapy in patients with early Parkinson's disease. In the symptomatic treatment of early Parkinson's disease ropinirole monotherapy was significantly more effective than placebo in 2 multicentre, randomised, double-blind trials of 3 to 12 months duration as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and Clinical Global Impression/Clinical Global Evaluation Scales. In a similarly designed 3-year comparative study with bromocriptine, ropinirole recipients showed a significant improvement in UPDRS- activities of daily living (ADL) scores; however, motor scores were similar between the 2 groups. Ropinirole and levodopa treatments were similar in efficacy as measured by UPDRS ADL scores, although ropinirole recipients showed significantly less improvement on UPDRS motor scores at the 5-year study end-point in a multicentre, randomised double-blind trial. As an adjunct therapy to levodopa in patients with more advanced Parkinson's disease, ropinirole was reported to be as effective as bromocriptine and significantly more effective than placebo. In general in the comparisons with placebo ropinirole allowed a > or =20% reduction in the concomitant dose of levodopa without compromising efficacy in a significant proportion of patients and, in some trials decreased the amount of awake time spent in the 'off' state ('off' state is defined as a gradual return to parkinsonism despite adequate medication). Ropinirole was well tolerated either as monotherapy or as an adjunct to levodopa treatment. Nausea, dizziness and somnolence were the most commonly reported adverse events and were reported at a higher

  4. Dopamine agents for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Junker, Anders Ellekær; Als-Nielsen, Bodil; Gluud, Christian


    BACKGROUND: Patients with hepatic encephalopathy may present with extrapyramidal symptoms and changes in basal ganglia. These changes are similar to those seen in patients with Parkinson's disease. Dopamine agents (such as bromocriptine and levodopa, used for patients with Parkinson's disease) have...... therefore been assessed as a potential treatment for patients with hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful effects of dopamine agents versus placebo or no intervention for patients with hepatic encephalopathy. SEARCH METHODS: Trials were identified through the Cochrane...... of the trials followed participants after the end of treatment. Only one trial reported adequate bias control; the remaining four trials were considered to have high risk of bias. Random-effects model meta-analyses showed that dopamine agents had no beneficial or detrimental effect on hepatic encephalopathy...

  5. Case of Combination of Hyperprolactinemic Hypogonadism and Mosaic Turner Syndrome

    Directory of Open Access Journals (Sweden)

    V.S. Vernyhorodskyi


    Full Text Available After detail examination of 24-year-old female patient (cariotype — 46XX/45XO, sex chromatin — 11 %, serum prolactin level — more than 200 mIU/ml (normal level — less than 26,72, ovarian ultrasound, geneticist consultation, magnetic resonance imaging of the hypophysis, the сlinical diagnosis was established: pituitary microadenoma. Hyperprolactinemic hypogonadism. Mosaic Turner syndrome. Genital infantilism. Infertility of endocrine origin. First menstruation occurred in 3 months, and pregnancy — in 4 month after initiation of the treatment with alactin 0.5 mg twice a week, after that bromocriptine 2.5 mg once a day was administered. On the 39–40th week of pregnancy, the patient gave birth to a girl (via cesarean section, whose weight was 3.4 kg and height — 48 cm.

  6. Rapid left ventricular recovery after cabergoline treatment in a patient with peripartum cardiomyopathy (United States)

    de Jong, Jonas S.S.G.; Rietveld, Kirsten; van Lochem, Laura T.; Bouma, Berto J.


    The aetiology of peripartum cardiomyopathy (PPCM) is still largely unknown. Recent evidence suggests that the breakdown products from prolactin can induce cardiomyopathy. Prolactin secretion can be reduced with bromocriptine which had beneficial effects in a small study. We present a case of a patient with PPCM who received cabergoline, a strong and long lasting antagonist of prolactin secretion. Following treatment, her prolactin levels dropped swiftly. N-terminal pro-BNP levels, which had remained high up to that point, dropped within 1 day (7006 to 4408 pg/mL). Echocardiographic left ventricular ejection fraction recovered from 26% on Day 4 postpartum to 32% and later 47% on Days 2 and 5 after cabergoline treatment. To our knowledge, this is the first description of a case of PPCM in which cabergoline was administered. PMID:19168522

  7. [Functional therapy]. (United States)

    De Lima, G R


    This article attempts to present and explain the therapy for the most common gynecological and nongynecological problems caused by oral contraception (OC). Carcinogenic side effects include vulvar and cervical cancer, which can be treated with cryosurgery, breast cancer, usually treated either by termination of OC, or by additional hormonal therapy, endometritis, and endometrial hyperplasia and adenocarcinoma, a result of the action of progesterone on tissues continuously stimulated by estrogen. Endocrinal aspects of OC include all menopausal syndromes, most dermatological side effects, such as acne and hirsutism, nonpuerperal galactorrhea, usually due to hyperprolactinemia, and which responds very well to treatment with bromocriptine, and infections such as herpes genitalis, candida albicans, and others. OC can also cause vulvar distrophy, to be treated with testosterone propionate, and anovulation, which responds very well to treatment with clomiphene.

  8. Recruitment of beta-arrestin2 to the dopamine D2 receptor: insights into anti-psychotic and anti-parkinsonian drug receptor signaling

    DEFF Research Database (Denmark)

    Klewe, Ib V; Nielsen, Søren M; Tarpø, Louise


    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 beta-arrestin. In this study we describe the establishment...... of a Bioluminescence Resonance Energy Transfer (BRET) assay for measuring dopamine induced recruitment of human beta-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 beta-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...

  9. Electroconvulsive therapy in drug resistant neuroleptic malignant syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Yousefi A


    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Neuroleptic malignant syndrome is an idiosyncratic and potentially fatal reaction to neuroleptic drugs and is characterized by fever, muscular rigidity, altered mental status, autonomic dysfunction, elevated serum CPK and leucocytosis Neuroleptic malignant syndrome is treated with dantrolene, bromocriptin, amantadin and electroconvulsive therapy."n"nCase: A 22 years old, schizophrenic female was refered to the Emergency ward of Roozbeh hospital in Tehran, Iran in December 2008 with aggression, impulsivity, and reduced sleep. After injection of haloperidol, the patient developed a high grade fever, diaphoresis and muscular stiffness. She was diagnosed as neuroleptic malignant syndrome and the treatment with dantrolen, bromocriptin and amantadin initiated. Although fever subsided, other signs continued, therefore we applied electroconvulsive therapy to this case."n"nConclusion: Due to excellent response of the patient to electroconvulsive therapy and the rare reports of electroconvulsive therapy in neuroleptic malignant syndrome in the Iranian population, this case may lead to develop studies for further investigations of this issue.

  10. Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells. (United States)

    Cussac, Didier; Boutet-Robinet, Elisa; Ailhaud, Marie-Christine; Newman-Tancredi, Adrian; Martel, Jean-Claude; Danty, Nathalie; Rauly-Lestienne, Isabelle


    Several examples of agonist-directed trafficking of receptor signalling at 5-HT2A and 5-HT2C receptors have been reported that involve independent downstream transduction pathways. We now report the functional selectivity of a series of chemically diverse agonists at human (h)5-HT2A, h5-HT2B and h5-HT2C-VSV by examining two related responses, the upstream activation of Gq/11 proteins in comparison with its associated cascade of calcium mobilisation. At the h5-HT2A receptor, d-lysergic acid diethylamide (LSD) and the antiparkinsonian agents lisuride, bromocriptine and pergolide exhibit a higher potency for Gq/11 activation than calcium release in contrast with all the other tested ligands such as 5-HT, mCPP and BW723C86, that show an opposite preference of signalling pathway. Comparable observations are made at h5-HT2B and h5-HT2C-VSV receptors, suggesting a similar mechanism of functional selectivity for the three serotonin receptors. Interestingly, the non-hallucinogenic compound lisuride behaves as a partial agonist for both Gq/11 activation and calcium release at the three 5-HT2 receptors, in contrast with DOI, LSD, pergolide and bromocriptine, which are known to provoke hallucinations, and behave as more efficacious agonists. Hence, a functional selectivity for Gq/11 activation together with a threshold of efficacy at h5-HT2A (and possibly h5-HT2B and/or h5-HT2C-VSV) may contribute to hallucinogenic liability. Thus, our results extend the notion of agonist-directed trafficking of receptor signalling to all the 5-HT2-receptor family and indicate that measures of Gq/11 activation versus calcium release may be useful to identify more effective therapeutic drugs with limited side effects.

  11. Dopaminergic drugs in type 2 diabetes and glucose homeostasis. (United States)

    Lopez Vicchi, Felicitas; Luque, Guillermina Maria; Brie, Belen; Nogueira, Juan Patricio; Garcia Tornadu, Isabel; Becu-Villalobos, Damasia


    The importance of dopamine in central nervous system function is well known, but its effects on glucose homeostasis and pancreatic β cell function are beginning to be unraveled. Mutant mice lacking dopamine type 2 receptors (D2R) are glucose intolerant and have abnormal insulin secretion. In humans, administration of neuroleptic drugs, which block dopamine receptors, may cause hyperinsulinemia, increased weight gain and glucose intolerance. Conversely, treatment with the dopamine precursor l-DOPA in patients with Parkinson's disease reduces insulin secretion upon oral glucose tolerance test, and bromocriptine improves glycemic control and glucose tolerance in obese type 2 diabetic patients as well as in non diabetic obese animals and humans. The actions of dopamine on glucose homeostasis and food intake impact both the autonomic nervous system and the endocrine system. Different central actions of the dopamine system may mediate its metabolic effects such as: (i) regulation of hypothalamic noradrenaline output, (ii) participation in appetite control, and (iii) maintenance of the biological clock in the suprachiasmatic nucleus. On the other hand, dopamine inhibits prolactin, which has metabolic functions; and, at the pancreatic beta cell dopamine D2 receptors inhibit insulin secretion. We review the evidence obtained in animal models and clinical studies that posited dopamine receptors as key elements in glucose homeostasis and ultimately led to the FDA approval of bromocriptine in adults with type 2 diabetes to improve glycemic control. Furthermore, we discuss the metabolic consequences of treatment with neuroleptics which target the D2R, that should be monitored in psychiatric patients to prevent the development in diabetes, weight gain, and hypertriglyceridemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Dopamine inhibits mitochondrial motility in hippocampal neurons.

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    Sigeng Chen


    Full Text Available The trafficking of mitochondria within neurons is a highly regulated process. In an earlier study, we found that serotonin (5-HT, acting through the 5-HT1A receptor subtype, promotes axonal transport of mitochondria in cultured hippocampal neurons by increasing Akt activity, and consequently decreasing glycogen synthase kinase (GSK3beta activity. This finding suggests a critical role for neuromodulators in the regulation of mitochondrial trafficking in neurons. In the present study, we investigate the effects of a second important neuromodulator, dopamine, on mitochondrial transport in hippocampal neurons.Here, we show that dopamine, like 5-HT, regulates mitochondrial motility in cultured hippocampal neurons through the Akt-GSK3beta signaling cascade. But, in contrast to the stimulatory effect of 5-HT, administration of exogenous dopamine or bromocriptine, a dopamine 2 receptor (D2R agonist, caused an inhibition of mitochondrial movement. Moreover, pretreatment with bromocriptine blocked the stimulatory effect of 5-HT on mitochondrial movement. Conversely, in cells pretreated with 5-HT, no further increases in movement were observed after administration of haloperidol, a D2R antagonist. In contrast to the effect of the D2R agonist, addition of SKF38393, a dopamine 1 receptor (D1R agonist, promoted mitochondrial transport, indicating that the inhibitory effect of dopamine was actually the net summation of opposing influences of the two receptor subtypes. The most pronounced effect of dopamine signals was on mitochondria that were already moving directionally. Western blot analysis revealed that treatment with either a D2R agonist or a D1R antagonist decreased Akt activity, and conversely, treatment with either a D2R antagonist or a D1R agonist increased Akt activity.Our observations strongly suggest a role for both dopamine and 5-HT in regulating mitochondrial movement, and indicate that the integrated effects of these two neuromodulators may be

  13. Efficacy of quinagolide in resistance to dopamine agonists: results of a multicenter study. Club de l'Hypophyse. (United States)

    Rohmer, V; Freneau, E; Morange, I; Simonetta, C


    A retrospective French multicenter analysis was carried out to assess changes in tumor volume and plasma prolactin concentration in order to evaluate the efficacy of quinagolide (Norprolac) in patients with prolactinoma resistant to ergot dopamine agonists. One hundred seven patients (46 men and 61 women) from 27 centers were included in the statistical analysis. All had previously been treated with a dopamine agonist (bromocriptine). Fifty-five patients had undergone surgery before being administered quinagolide: 17 of the patients had also received radiotherapy (before and after the initiation of treatment with quinagolide in 14 and 3 cases respectively). Quinagolide was given at doses ranging from 75 to 750 microg daily and continued for more than one year for 84 patients. The prolactin level returned to normal after a mean interval of 9.8 1.6 months (1-48) in 47 of the 107 patients (44%) using a mean dose of quinagolide of 259 32.7 microg/d (75-750). The plasma prolactin concentration had already been normalized using bromocriptine in three patients. The variation in tumor volume was assessed in 82 patients since 8 had no residual tumor post-operatively and 17 had received radiotherapy: at least partial regression of the tumor was noted in 25 (30.8%), including 16 (19.5%) with a more than 50% decrease in the remaining tumor. The mean time taken to observe the anti-tumoral effect was 16.8 3.1 months (3-78) using a mean dose of quinagolide of 255.4 37.8 microg/d d (75-750). The following predictive indicators were identified concerning the efficacy of quinagolide: a pre-quinagolide prolactin level ofresistant prolactinoma.

  14. Cocaine-associated stroke: three cases and rehabilitation considerations. (United States)

    Tolat, R D; O' Dell, M W; Golamco-Estrella, S P; Avella, H


    Cocaine-associated stroke (CAS) is an important cause of disability, especially among younger adults. Improved management has increased survival but little has been discussed about rehabilitation, including medication management. Therefore, experience and therapeutic drug management are described during inpatient rehabilitation with three patients with CAS. Case 14 is a 50-year-old male with a history of hypertension who presented with right hemiparesis, aphasia and depression. He was treated with paroxetine for depression and bromocriptine for poor initiation with a good response, improving by 50 FIM points in 44 days. Case 2 is a 44 year-old female with quadriparesis, aphasia, and deficits in attention and initiation. Methylphenidate for attention deficits and bromocriptine for poor initiation was associated with an excellent functional gain (50 FIM points in 37 days). She eventually returned to work. Case 3 is a 46-year-old female with a history of hypertension who presented with right hemiparesis, aphasia and depression. Without neuropharmacologic intervention, she gained 35 FIM points during an uneventful 47 day rehabilitation stay. Acutely, cocaine can induce cerebral vasoconstriction, cerebrovascular spasm, cerebral vasculitis and intracerebral haemorrhage. Chronic use depletes and destroys dopaminergic pathways, which may be a major factor in depression, and attention and initiation deficits-all observed in these cases. Generally, rapid improvements were seen in mood and cognition in two cases where medication was used. Based on the current literature and pathophysiology of CAS, it is suggested that trials of dopaminergic agents for cognition and extremely cautious use of buproprion for depression may be warrented. Details of the above cases and the practical and theoretical issues of neuropharmacologic intervention in CAS are discussed.

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

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


    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.

  16. Treatment of hyperprolactinemia: a systematic review and meta-analysis

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    Wang Amy T


    Full Text Available Abstract Background Hyperprolactinemia is a common endocrine disorder that can be associated with significant morbidity. We conducted a systematic review and meta-analyses of outcomes of hyperprolactinemic patients, including microadenomas and macroadenomas, to provide evidence-based recommendations for practitioners. Through this review, we aimed to compare efficacy and adverse effects of medications, surgery and radiotherapy in the treatment of hyperprolactinemia. Methods We searched electronic databases, reviewed bibliographies of included articles, and contacted experts in the field. Eligible studies provided longitudinal follow-up of patients with hyperprolactinemia and evaluated outcomes of interest. We collected descriptive, quality and outcome data (tumor growth, visual field defects, infertility, sexual dysfunction, amenorrhea/oligomenorrhea and prolactin levels. Results After review, 8 randomized and 178 nonrandomized studies (over 3,000 patients met inclusion criteria. Compared to no treatment, dopamine agonists significantly reduced prolactin level (weighted mean difference, -45; 95% confidence interval, -77 to −11 and the likelihood of persistent hyperprolactinemia (relative risk, 0.90; 95% confidence interval, 0.81 to 0.99. Cabergoline was more effective than bromocriptine in reducing persistent hyperprolactinemia, amenorrhea/oligomenorrhea, and galactorrhea. A large body of noncomparative literature showed dopamine agonists improved other patient-important outcomes. Low-to-moderate quality evidence supports improved outcomes with surgery and radiotherapy compared to no treatment in patients who were resistant to or intolerant of dopamine agonists. Conclusion Our results provide evidence to support the use of dopamine agonists in reducing prolactin levels and persistent hyperprolactinemia, with cabergoline proving more efficacious than bromocriptine. Radiotherapy and surgery are useful in patients with resistance or intolerance

  17. Dopamine Modulates Adaptive Prediction Error Coding in the Human Midbrain and Striatum. (United States)

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


    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

  18. Long-term in-vitro treatment of human growth hormone (GH)-secreting pituitary adenoma cells with octreotide causes accumulation of intracellular GH and GH mRNA levels. (United States)

    Hofland, L J; Velkeniers, B; vd Lely, A J; van Koetsveld, P M; Kazemzadeh, M; Waaijers, M; Hooghe-Peters, E L; Lamberts, S W


    We studied the effects of long-term in-vitro exposure of human GH secreting pituitary adenoma cells to octreotide on GH release, intracellular GH concentrations and GH messenger ribonucleic acid (mRNA) levels. Human GH-secreting pituitary adenoma cells were cultured for periods from 4 days up to 3 weeks without or with octreotide (10 nM) and/or bromocriptine (10 nM). The effects of these drugs were measured on GH release, intracellular GH concentrations and intracellular GH mRNA levels. Thirteen patients with GH-secreting pituitary adenomas were studied. Twelve patients were untreated, one had been pretreated with octreotide (12 weeks, 3 x 100 micrograms daily). GH, PRL, alpha-subunit and IGF-I concentrations in plasma, media and cell extracts were determined by immunoradiometric or radioimmuno-assays. GH mRNA levels were determined by automatic quantification of grain numbers in individual adenoma cells. Incubation of the adenoma cells for 4 days with 10 nM octreotide induced a dose-dependent inhibition of GH release and a parallel increase (increase varying between 124 and 617% of control) in the intracellular GH levels was observed in six of seven adenomas. In addition, bromocriptine, when effective in inhibiting GH release by the adenomas, also induced an increase in intracellular GH levels. Even after 3 weeks of exposure to 10 nM octreotide in vitro there was a statistically significant increase in intracellular GH levels (between 191 and 923% of control). Withdrawal of octreotide after 6 days of incubation resulted in a lowering of intracellular GH levels to control values, showing that the octreotide-induced increase in intracellular GH is reversible. In a 96-hour incubation with 10 nM octreotide, GH mRNA levels were increased in two, and slightly decreased in one of the three adenomas tested. This effect was time dependent in that there was no significant effect of 10 nM octreotide on GH mRNA levels in a 24-hour incubation. (1) Long-term in-vitro exposure

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

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


    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 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

  20. iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease

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    Takayuki Kondo


    Full Text Available In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer’s disease (AD. Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ, a pathogenic molecule in AD, and screened a pharmaceutical compound library. We acquired 27 Aβ-lowering screen hits, prioritized hits by chemical structure-based clustering, and selected 6 leading compounds. Next, to maximize the anti-Aβ effect, we selected a synergistic combination of bromocriptine, cromolyn, and topiramate as an anti-Aβ cocktail. Finally, using neurons from familial and sporadic AD patients, we found that the cocktail showed a significant and potent anti-Aβ effect on patient cells. This human iPSC-based platform promises to be useful for AD drug development.

  1. A follow-up of 130 patients with acromegaly in a single centre. (United States)

    Bolanowski, Marek; Zatonska, Katarzyna; Kaluzny, Marcin; Zielinski, Grzegorz; Bednarek-Tupikowska, Grazyna; Bohdanowicz-Pawlak, Anna; Daroszewski, Jacek; Szymczak, Jadwiga; Podgorski, Jan Krzysztof


    Acromegaly is a rare disease with increased mortality rate. The aim was to present our centre experience in the diagnosis and treatment of a series of patients suffering from acromegaly. 130 patients (55 men, 75 women) aged 19-84 years presenting with clinical and hormonal features of acromegaly, attending Department of Endocrinology and Out-patient Clinic between 1990 and 2004 were studied. They were analyzed their GH and IGF-1 levels, CT and MRI scans, and they were administered medical therapy, neurosurgery and radiotherapy. We have observed 106 macro-, 16 microadenomas and 1 case of ectopic GHRH. 115 patients were operated, as cured were recognized 74 of them. Pituitary irradiation was applied to 11 patients, in 4 of them it did not cure the disease. Medical therapy was efficacious in 12% patients treated with bromocriptine, 73% with long-acting lanreotide and 58% with long-acting octreotide. In 7 patients other malignant neoplasm were detected. 11 patients died during the follow-up. There is possible underdiagnosis of acromegaly in our region, especially in males. We have observed better diagnostic opportunities in recent years when MRI was available. It was accompanied by better outcome of surgical and pharmacological treatment and better control of the complications of the disease.

  2. Lisuride hydrogen maleate: evidence for a long lasting dopaminergic activity in humans. (United States)

    Liuzzi, A; Chiodini, P G; Oppizzi, G; Botalla, L; Verde, G; De Stefano, L; Colussi, G; Gräf, K J; Horowski, R


    In 12 acromegalics a single oral dose of 0.2 mg lisuride, an ergoline derivative, significantly reduced plasma PRL but not GH concentrations. Three-tenths milligram of the drug significantly reduced plasma levels of the two hormones. Four-tenths milligram of lisuride did not augment this inhibitory effect. Plasma PRL levels were suppressed in all patients, whereas GH levels were reduced by more than 50% of the base-line values in only seven patients who also responded to the administration of 2.5 mg bromocriptine (CB154). In the patients unresponsive to lisuride, CB154 also failed to change GH levels. The suppressive effect of lisuride started at 60 min (at 150 min for CB154) and plasma GH and PRL levels were still markedly suppressed at 300 min. Plasma GH and PRL concentrations were consistently reduced in two acromegalic patients during 2 weeks of chronic treatment with 0.3 mg lisuride four times a day. In six normal subjects, TRH-induced PRL release was significantly inhibited by pretreatment with 0.3 mg of the drug. The similarity in the effects of lisuride and CB154 suggests that the observed effects of lisuride on GH and PRL are attributable to the known dopaminergic activity of the drug. This conclusion is supported by the data showing that pimozide effectively counteracted the inhibitory action of lisuride on GH and PRL release. We suggest that lisuride may be of value in the medical treatment of acromegaly and hyperprolactinemic states.

  3. Changes in Plasma Prolactin and Growth Hormone Level and Visual Problem after radiation Therapy(RT) of Pituitary Adenoma

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    Yoon, Sei Chul; Kwon, Hyung Chul; Oh, Yoon Kyeong; Bahk, Yong Whee; Son, Ho Young; Kang, Joon Ki; Song, Jin Un [Catholic Medical College, Seoul (Korea, Republic of)


    Twenty-four cases of pituitary adenoma, 13 males and 11 females with the age ranging from 11 to 65 years, received radiation therapy(RT) on the pituitary area with 6MV linear accelerator during past 25 months at the Division of Radiation Therapy, Kangnam St. Mary Hospital, Catholic Medical College. Of 24 case of RT, 20 were postoperative and 4 primary. To evaluate the effect of RT, we analyzed the alteration of the endocrinological tests, neurologic abnormalities, major clinical symptoms, endocrinological changes and improvement in visual problems after RT. The results were as follows ; 1. Major clinical symptoms were headache, visual defects, diabetes insipidus, hypogonadisms and general weakness in decreasing order of frequency. 2. All but the one with Nelson syndrome showed abnormal neuroradiologic changes in the sella turcica with an invasive tumor mass around supra and para-sellar area. 3. Endocrinological classifications of the patient were 11 prolactinoma, 4 growth hormonesecreting tumors, 3 ACTH-secreting tumors consisting of one Cushing disease and two Nelson syndrome, and 6 nonfunctioning tumors. 4. Eleven of 14 patients, visual problems were improved after treatment but remaining 3 were unchanged. 5. Seven of 11 prolactinomas returned to normal hormonal level after postoperative and primary RT and 3 patients are being treated with bromocriptine (BMCP) but on lost case. 6. Two of 4 growth hormone-secreting tumor returned to normal level after RT but the remaining 2 are being treated with BMCP, as well.

  4. Peripartum cardiomyopathy: a review. (United States)

    Bhattacharyya, Anirban; Basra, Sukhdeep Singh; Sen, Priyanka; Kar, Biswajit


    Peripartum cardiomyopathy is idiopathic heart failure occurring in the absence of any determinable heart disease during the last month of pregnancy or the first 5 months postpartum. The incidence varies worldwide but is high in developing nations; the cause of the disease might be a combination of environmental and genetic factors. Diagnostic echocardiographic criteria include left ventricular ejection fraction 2.7 cm/m(2). Electrocardiography, magnetic resonance imaging, endomyocardial biopsy, and cardiac catheterization aid in the diagnosis and management of peripartum cardiomyopathy. Cardiac protein assays can also be useful, as suggested by reports of high levels of NT-proBNP, cardiac troponin, tumor necrosis factor-α, interleukin-6, interferon-γ, and C-reactive protein in peripartum cardiomyopathy. The prevalence of mutations associated with familial dilated-cardiomyopathy genes in patients with peripartum cardiomyopathy suggests an overlap in the clinical spectrum of these 2 diseases.Treatment for peripartum cardiomyopathy includes conventional pharmacologic heart-failure therapies-principally diuretics, angiotensin-converting enzyme inhibitors, vasodilators, digoxin, β-blockers, anticoagulants, and peripartum cardiomyopathy-targeted therapies. Therapeutic decisions are influenced by drug-safety profiles during pregnancy and lactation. Mechanical support and transplantation might be necessary in severe cases. Targeted therapies (such as intravenous immunoglobulin, pentoxifylline, and bromocriptine) have shown promise in small trials but require further evaluation. Fortunately, despite a mortality rate of up to 10% and a high risk of relapse in subsequent pregnancies, many patients with peripartum cardiomyopathy recover within 3 to 6 months of disease onset.

  5. Benign breast disease. (United States)

    Hamed, H; Fentiman, I S


    Benign breast disorders (BBD), classified by the ANDI system (aberrations of normal development and involution), constitute the major workload in breast clinics. Breast pain (mastalgia) is classified as cyclical, and non-cyclical extramammary causes such as ribircage pain have to be identified. Most patients need reassurance alone but those with moderate/severe pain present for > 6 months may need treatment: randomised trials have shown danazol, bromocriptine and tamoxifen to be effective. Fibroadenoma is the commonest benign solid lump in women aged 15-30 years. The diagnosis must be confirmed by triple assessment. Cysts occur usually in women of middle to late reproductive life. After ultrasound has confirmed the lump as cystic, it can be aspirated. Nipple discharge should be tested for the presence of haemoglobin (Hb). Those with HB+ discharge may require microdochectomy for treatment and diagnosis, common causes being duct papilloma and duct ectasia. Breast abscesses may occur during lactation or in women with duct ectasia and are treated by incision or aspiration together with antibiotics.

  6. Dopaminergic drug effects during reversal learning depend on anatomical connections between the orbitofrontal cortex and the amygdala.

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    Marieke E. van der Schaaf


    Full Text Available Dopamine in the striatum is known to be important for reversal learning. However, the striatum does not act in isolation and reversal learning is also well accepted to depend on the orbitofrontal cortex (OFC and the amygdala. Here we assessed whether dopaminergic drug effects on human striatal BOLD signalling during reversal learning is associated with anatomical connectivity in an orbitofrontal-limbic-striatal network, as measured with diffusion tensor imaging. By using a fibre-based approach, we demonstrate that dopaminergic drug effects on striatal BOLD signal varied as a function of fractional anisotropy (FA in a pathway connecting the OFC with the amygdala. Moreover, our experimental design allowed us to establish that these white-matter dependent drug effects were mediated via D2 receptors. Thus, white matter dependent effects of the D2 receptor agonist bromocriptine on striatal BOLD signal were abolished by co-administration with the D2 receptor antagonist sulpiride. These data provide fundamental insight into the mechanism of action of dopaminergic drug effects during reversal learning. In addition, they may have important clinical implications by suggesting that white matter integrity can help predict dopaminergic drug effects on brain function, ultimately contributing to individual tailoring of dopaminergic drug treatment strategies in psychiatry.

  7. Development of pituitary adenoma treatment--a critical essay. (United States)

    Landolt, A M


    The history of pituitary adenoma treatment shows, as in medicine in general, a succession of movements and counter movements. A large number of surgical techniques was proposed, but only very few survived the selection process. This selection was influenced not only by the general development of surgical techniques that also by the introduction of effective medical treatments and the arrival of new diagnostic methodology. We witness today a new selection mechanism besides the quality of the results--the economic pressure. Its importance may even increase in future because of progressing limitations of medical budgets. We subdivide the history of pituitary adenoma treatment into three main periods: the early period from Sir Victor Horsley to Norman Dott; the period of the reintroduction of the transphenoidal approach initiated by Gérard Guiot to the introduction of bromocriptine, the first effective antisecretory drug; and the period of refinement of the individual treatment methods still going on today. We present this history not so much in a retrospective way, by enumerating the single technical variations of surgical procedures but rather by presenting the momentary situations, as witnessed by our predecessors by presenting short extracts of contemporary texts to characterize the thinking in the past.

  8. Dopaminergic therapy in aphasia. (United States)

    Gill, Sumanjit K; Leff, Alexander P


    The dopaminergic system is involved in a wide range of cognitive functions including motor control, reward, memory, attention, problem-solving and learning. This has stimulated interest in investigating the potential of dopaminergic drugs as cognitive enhancers in aphasic patients. To discuss the evidence for the use of dopaminergic agents in patients with aphasia. Levodopa (L-dopa) and the dopamine agonist bromocriptine are the two drugs that have been trialled to date. We discuss, in some detail, the 15 studies that have been published on this topic from the first case report in 1988 to the present (2012), and assess the evidence from each. In addition to summarising the effectiveness of the drugs that have been tried, we examine the possible cognitive mechanisms by which dopaminergic drugs may act on language function and aphasia recovery. Given the wide range of dopaminergic drugs, it is surprising that such a narrow range has been trialled in aphasic patients. Important lessons are to be learned from published studies and we discuss optimal trial designs to help guide future work. The evidence for the efficacy of dopaminergic agents in aphasia therapy is mixed. Further trials with better tolerated agents are required. Optimal trial designs with appropriate control groups or blocks should be used. The mechanism of action is unclear, but at the cognitive level the evidence points towards either (re)learning of word-forms or their improved retrieval.

  9. Morphologic effects of cysteamine on the rat adenohypophysis

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    Cairns, P.D.; McComb, D.J.; Horvath, E.; Kovacs, K.; Milligan, J.V.; Szabo, S.


    In pituitary lactotrophs of female Sprague-Dawley rats given cysteamine (300 mg/kg, per os/day) for 7 days, forming granules were increased in number and contained many separate electron-dense structures suggesting crinophagy. Compared to control values, cysteamine treatment caused no change in blood prolactin (PRL) levels, measured by radioimmunoassay (RIA). 17 beta-Estradiol (50 micrograms, sc/day) for 7 days, induced lactotroph hyperplasia and increased blood PRL levels which were unaffected by simultaneous cysteamine administration. The ultrastructural changes did not reflect those due to bromocriptine suppression of secretory activity, and supported the concept that cysteamine altered lactotroph morphology by an unknown mechanism. In pituitary gonadotrophs following cysteamine treatment, increased electron lucency of luminal contents of dilated rough endoplasmic reticulum was noted; however, blood luteinizing hormone (LH) levels did not differ from those of control values. In ovariectomized rats, cysteamine suppressed castration cell formation and reduced blood LH levels, suggesting an interference with the cell's ability to respond to GnRH stimulation. The morphologic effects of cysteamine appeared to be selective to lactotrophs and gonadotrophs, and were not secondary to vascular impairment, as capillary endothelial cells were undamaged.

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

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    C. Weiss


    Full Text Available 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.

  11. Prolactin and glucocorticoid signaling induces lactation-specific tight junctions concurrent with β-casein expression in mammary epithelial cells. (United States)

    Kobayashi, Ken; Tsugami, Yusaku; Matsunaga, Kota; Oyama, Shoko; Kuki, Chinatsu; Kumura, Haruto


    Alveolar mammary epithelial cells (MECs) in mammary glands are highly specialized cells that produce milk for suckling infants. Alveolar MECs also form less permeable tight junctions (TJs) to prevent the leakage of milk components after parturition. In the formation process of less permeable TJs, MECs show a selective downregulation of Cldn4 and a localization change of Cldn3. To investigate what induces less permeable TJs through these compositional changes in Cldns, we focused on two lactogenesis-related hormones: prolactin (Prl) and glucocorticoids. Prl caused a downregulation of Cldn3 and Cldn4 with the formation of leaky TJs in MECs in vitro. Prl-treated MECs also showed low β-casein expression with the activation of STAT5 signaling. By contrast, dexamethasone (Dex), a glucocorticoid analogue, upregulated Cldn3 and Cldn4, concurrent with the formation of less permeable TJs and the activation of glucocorticoid signaling without the expression of β-casein. Cotreatment with Prl and Dex induced the selective downregulation of Cldn4 and the concentration of Cldn3 in the region of TJs concurrent with less permeable TJ formation and high β-casein expression. The inhibition of Prl secretion by bromocriptine in lactating mice induced the upregulation of Cldn3 and Cldn4 concurrent with the downregulation of milk production. These results indicate that the coactivation of Prl and glucocorticoid signaling induces lactation-specific less permeable TJs concurrent with lactogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Peripartum cardiomyopathy

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    Rodolfo Citro


    Full Text Available Peripartum cardiomyopathy is an uncommon form of congestive heart failure associated with systolic dysfunction of left ventricle. The onset is characterised by symptoms of heart failure occurring between the last month of pregnancy and 5-6 months postpartum. The early diagnosis and the institution of medical treatment for this disease are essential because the inadequate management may affect the patient’s long-term prognosis and can lead to severe complications, including death.Currently its aetiology is not completely understood. Many aetiopathogenetic hypotheses have been formulated: inflammation, viral agents, autoimmune processes. In the last years, evidences aroused for a role of prolactin and its 16 kDa metabolite in reducing cardiomyocite metabolic activity and contraction. In this article we have reviewed the current literature with special emphasis on the role of prolactin and the related current treatment strategies. In particular, bromocriptine appears promising, even if women need to be informed that the drug stops the production of breastmilk. Further researchers, such as large multicenter trials, are needed to decide the best treatment for the women suffering of this disease.

  13. Galactorrea grave tras aumento mamario con implantes Severe galactorrhea after mammary augmentation with implants

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    F.T. Fidalgo Rodríguez


    Full Text Available La galactorrea es una complicación poco frecuente después de la cirugía plástica mamaria. Su causa aun es desconocida, aunque lo más probable es que su aparición tenga un origen multifactorial. En el caso que presentamos la paciente desarrolló incremento simétrico del volumen de ambas mamas después de un cirugía de aumento mamario. No se detectaron cambios en los valores de prolactina. El proceso no respondió al tratamiento con bromocriptina. La galactorrea postquirúrgica con frecuencia sigue un curso benigno y autolimitado, culminando con resolución espontánea. Dependiendo de la severidad de los síntomas, su tratamiento puede ser médico y/o quirúrgico, con drenaje o incluso retirada de los implantes mamarios.Galactorrhea is a complication rarely observed after mammary plastic surgery. The cause remains unknown although it's likely to be multifactorial. In the reported case, the patient described symmetric massive engorgement of both breasts after augmentation mammoplasty. No significant change was detected in the postoperative prolactin values. The condition was unresponsive to treatment with bromocriptine. Postsurgical galactorrhea often follows a benign course culminating in spontaneous resolution Depending on symptom severity, treatment may be medical with the prescription of dopaminergic agonists, and/or surgical with drainage or even removal of the mammary implants.

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

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    Shadi Rezai


    Full Text Available 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.

  15. A systematic review on clinical management of antipsychotic-induced sexual dysfunction in schizophrenia

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    Anna Maria Niccolai Costa

    Full Text Available INTRODUCTION: Sexual dysfunction frequently occurs in patients with schizophrenia under antipsychotic therapy, and the presence of sexual side effects may affect compliance. The aim of this study was to review and describe clinical findings relating to the appropriate management of such dysfunctions. MATERIAL AND METHODS: The research was carried out through Medline (from 1966 to March 2005, PsycInfo (from 1974 to March 2005, and Cochrane Library (from 1965 to March 2005 and included any kind of study, from case reports to randomized trials. RESULTS: The most common sexual dysfunctions found in the literature were libido decrease, difficulties in achieving and maintaining erection, ejaculatory dysfunction, orgasmic dysfunction, and menstrual irregularities. Thirteen papers were found: eight of them were open-label studies, four were descriptions of cases, and only one was a randomized clinical trial. All of them were short-term and had small sample sizes. The agents used were: bromocriptine, cabergoline, cyproheptadine, amantadine, shakuyaku-kanzo-to, sildenafil and selegiline. DISCUSSION: There was no evidence that those agents had proper efficacy in treating the antipsychotic-induced sexual dysfunction. An algorithm for managing sexual dysfunction induced by antipsychotics is suggested as a support for clinical decisions. Since the outcome from schizophrenia treatment is strongly related to compliance with the antipsychotics, prevention of sexual dysfunction is better than its treatment, since there is a scarcity of data available regarding the efficacy of intervention to deal with these problems.

  16. Neuropharmacology In Individual With Aphasia: A Review

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    Mohammad Rezaei


    Full Text Available Introduction: The neuropharmacology of aphasia is an area of cognitive neuroscience. In this article we review what is known about these domain, especially with regard to treating aphasia with drugs. Neurotransmitters can improve language function in certain patients with aphasia. We discuss which neurotransmitters work for which language functions in which patients. Method: PubMed and Science databases were searched to identify studies investigated effects of drugs on language function in aphasia in peer-reviewed journals between 2000 and 2015.   Results: Studies show that Catecholamines seem especially promising for nonfluent aphasias. Dopamine agonists, in particular bromocriptine, improve verbal fluency in transcortical motor aphasia. Norepinephrine affects prefrontal functions and seems to relieve symptoms of depression and improve overall recovery of function, including language, following stroke. Amphetamines potentiate norepinephrine to promote general recovery, and have been shown to improve language performance in some patients with nonfluent aphasia. Conclusion: studies have been looking at the possibility of manipulating brain chemistry for functional gain in patients with aphasia, but, to date, no overwhelming evidence has emerged to support routine use of drugs as either a complementary or alternative treatment for aphasia. Studies have been largely anecdotal with small numbers of patients and varying types of aphasia. Improvements due to spontaneous recovery have been difficult to separate from treatment benefits.

  17. Rehabilitation of Schizophrenia: Adjunctive Therapy of Negative Symptoms

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    Saeed Shoja Shafti


    Full Text Available Negative symptoms in schizophrenia are among the important barriers against psychosocial rehabilitation of such patients. Adjunctive drugs can be used for reducing the severity of these symptoms. In this research we studied the efficacy of Clomipramine, Alprazolam, Citalopram, Bromocriptine, Fluoxetine, Nortriptyline, Maprotiline and Fluvoxamine, in this regard. After a primary prevalence survey regarding Negative symptoms, 170 schizophrenic patients were divided into three different groups, and then the aforesaid adjuvant drugs were examined in three double-blind clinical controlled trials. Estimation of negative symptoms by "SANS" were done at the beginning of each trial for the first time and then three weeks later, after prescription of drugs in lower dosage and finally at the end of sixth week, means three weeks after doubling the dosages. The data were analyzed by z and chi-square (X2test formula. Clomipramine, Alprazolam, Citalopram, Nortriptyline and Maprotiline could reduce the severity of negative symptoms. Their effectiveness in comparing with placebo was statistically remarkable. No important side effect or worsening of positive symptoms was seen in our samples during aforesaid trials. Conservative usage of adjuvant drugs can be an advantageous means for making rehabilitative programs more efficacious than before.

  18. Effect of LH and prolactin on steroid secretion by perifused luteal tissue from pregnant gilts with induced hypoprolactinemia or after passive immunoneutralization of LH

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    Szafranska, B.; Przala, J. [Akademia Rolniczo-Technicza, Olsztyn (Poland); Grazul-Bilska, A. [North Dakota State University, Fargo (United States)


    The study was performed using luteal tissue obtained from 24 pregnant gilts. Group 1 was treated with bromocriptine (BR) from 37th to 42nd day of day of pregnancy. Group 2 was treated with homologous anti-pLH serum from 37th to 42nd day of pregnancy. Group 3 was given BR from 67th to 72nd day of gestation. Group 4 received anti-pLH serum from 67th to 72nd day of pregnancy. The effect of exogenous LH or prolactin (100 ng/ml) on secretion of progesterone (P{sub 4}) and estradiol (E{sub 2}) by luteal tissue was studied using perfusion technique. Prolactin caused a significant (P<0.05) increase in P{sub 4} secretion by luteal tissue from gilts in groups 1 and 4. Both LH and prolactin decreased (P<0.05) estradiol secretion by luteal tissue obtained from gilts from group 4. Luteinizing hormone stimulated (P<0.05) P{sub 4} and E{sub 2} secretion by luteal tissue from gilts from groups 4 and 2, respectively. The results demonstrate that both LH and prolactin have a regulatory role in steroid secretion by luteal tissue of gilts in the mid- and late period of pregnancy. (author). 28 refs, 2 figs.

  19. Nutritional and hormonal regulation of malic enzyme synthesis in rat mammary gland. (United States)

    Lobato, M F; Ros, M; Moreno, F J; García-Ruíz, J P


    Cytosolic malic enzyme was purified from rat mammary gland by L-malate affinity chromatography. The pure enzyme obtained was used to produce a specific antiserum in a rabbit. Relative synthesis of malic enzyme in the mammary gland of mid-lactating rats was 0.097%, measured by labelling the enzyme in isolated acini. When food was removed, malic enzyme synthesis decreased to 35% and 20% of the control value at 4 and 6 h respectively. Incorporation of [3H]leucine into soluble proteins was constant during the first 6 h of starvation. When lactating rats (maintained with their pups) were starved for 24 h and then re-fed, the relative rate of enzyme synthesis increased 2.5-, 4-, and 4.5-fold at 3 h, 6 h and 18 h respectively after initiation of re-feeding. The relative rate of malic enzyme synthesis was about 50% of normal at 15 h after weaning, whereas the rate of synthesis of soluble proteins did not change. Administration of bromocriptine or adrenalectomy of lactating rats decreased the relative rate of synthesis of malic enzyme by 40% or 30% respectively; these effects were counteracted by hormone supplementation. Hormone therapy also caused an increase in the rate of incorporation of [3H]leucine into soluble proteins and in malic enzyme activity.

  20. Thyrotoxicosis due to pituitary resistance to thyroid hormones. Successful control with D thyroxine: a study in three patients. (United States)

    Dorey, F; Strauch, G; Gayno, J P


    Selective pituitary resistance to thyroid hormone (PRTH) is responsible for thyrotoxicosis due to inappropriate secretion of TSH. The TSH suppressive action of D-thyroxine (DT4) has been previously documented in euthyroid and hypothyroid subjects. This prompted us to treat with DT4 three patients with PRTH uncontrolled by anti-thyroid drugs (ATD) alone or supplemented with bromocriptine, and whose follow-up had been complicated by atrial fibrillation in two patients. Because of 100% cross-reactivity between the D and L isomers of T4 and T3 in our RIAs, thyroglobulin (Tg) was used as an index of thyroid secretion. Under ATD, TSH and Tg levels were respectively: 35 mIU/l and 670.5 pmol/l (patient 1), 87 mIU/l and 453 pmol/l (patient 2) and 110 mIU/l and 906 pmol/l (patient 3). When DT4 was added (patient 1, 3 mg daily; patients 2 and 3, 2 mg daily) to the same dose of ATD, plasma TSH and Tg levels fell but were still over the upper limit of normal and thyrotoxicosis persisted as illustrated by a recurrence of atrial fibrillation in one patient. When ATD were withdrawn and DT4 given alone (2 mg daily) all symptoms subsided within 1 month while TSH and Tg levels fell within the normal range. TSH normalization was documented within 1 week in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. 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. (United States)

    Hsieh, Wen-Ting; Chiang, Been-Huang


    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.

  2. Clinical course of hyperprolactinemia in children and adolescents: a review of 21 cases. (United States)

    Eren, Erdal; Yapıcı, Şenay; Çakır, Esra Deniz Papatya; Ceylan, Latife Aytekin; Sağlam, Halil; Tarım, Ömer


    Hyperprolactinemia may be due to various etiological factors and may present with different signs and symptoms. It is relatively less frequent in childhood than in adulthood. The aim of this study was to evaluate retrospectively the clinical course and outcome of hyperprolactinemia in pediatric patients. We investigated the records of 21 patients with hyperprolactinemia who attended a tertiary hospital. Menstrual problems, galactorrhea , and headache were the most common presenting symptoms. Hyperprolactinemia was due to microadenoma in 10, macroadenoma in 7, and was drug-induced in 4 patients. Bromocriptine and cabergoline were equally effective in lowering serum prolactin levels. Surgical treatment in children with macroprolactinoma was not curative and dopamine agonist therapy was required postoperatively. In the presence of any clinical symptom or sign suggestive of suppression of the pituitary-gonadal axis, hyperprolactinemia should not be forgotten as a probable diagnosis. Medical therapy seems effective in microadenoma. Surgical therapy may not be successful in macroadenoma and recurrence is frequent. ©Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing.

  3. [Early recurrent miscarriage: Evaluation and management]. (United States)

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


    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.

  4. Hepcidin levels in hyperprolactinemic women monitored by nanopore thin film based assay: correlation with pregnancy-associated hormone prolactin. (United States)

    Wang, Jing; Liu, Gang; Xu, Zi; Dai, Jiwei; Song, Ping; Shi, Jian; Hu, Ye; Hu, Zhongbo; Nie, Guangjun; Chang, Yan-Zhong; Zhao, Yuliang


    Hepcidin is a central regulator in human iron metabolism. Although it is often regarded as a promising indicator of iron status, the lack of effective quantification method has impeded the comprehensive assessment of its physiological and clinical significance. Herein we applied a newly established, nanopore film enrichment based hepcidin assay to examine the correlation between hepcidin and prolactin, the hormone with an important role during pregnancy and lactation. Women with pathologically elevated prolactin secretion (hyperprolactinemia) were found to have lower serum hepcidin compared to those with normal prolactin levels, without showing significant difference in other hepcidin-regulating factors. Moreover, prolactin-reducing drug bromocriptine mesylate resulted in elevated expression of the hepcidin in hyperprolactinemia patients. These findings suggest a possible role of prolactin in regulation of hepcidin, and may render hepcidin a useful biomarker for progress monitoring and treatment of iron-related diseases under hyperprolactinemic conditions. The level of hepcidin has been shown to reflect the underlying iron status of the patient. Nonentheless, there is an urgent need of reliable, fast and easy-to-do hepcidin assay in the clinical setting. In this paper, the authors described a further modification of their previously described nanopore silica film-based enrichment approach for quantification of hepcidin and found correlation between hepcidin and prolactin. This new knowledge may add to current understanding of iron homeostasis during pregnancy. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Review of awakening agents. (United States)

    DeMarchi, Ryan; Bansal, Vikas; Hung, Anthony; Wroblewski, Karol; Dua, Hemi; Sockalingam, Sanjeev; Bhalerao, Shree


    Brain injuries are a serious burden of illness to Canada and the US. Advances in managing head trauma have allowed more patients to emerge from decreased levels of consciousness and helped them cope with neurocognitive, neurobehavioural, and neuropsychiatric deficits. In this article, we review the current (1986-2002) evidence surrounding the pharmacological management of arousal states and the aforementioned neurological sequelae of head injury in either acute or chronic conditions. This article will review the evidence for the use of psychostimulants (methylphenidate), antidepressants (amitriptyline, selective serotonin reuptake inhibitors, and buproprion), Parkinson's medications (amantadine, bromocriptine, carbidopa/levodopa), anticonvulsants (valproic acid), modafinil (Provigil), lactate, hyperbaric oxygen chamber, electroconvulsive therapy, and transmagnetic stimulation, in patients following a head injury. The review did not include all anticonvulsants, neuroleptics, beta-blockers, benzodiazepines, azospirones or cognitive enhancers. Unfortunately, the quality of the evidence is generally poor, and sometimes conflicting, which in turn results in indecisive guidelines for treating patients. Accepting the inherent flaws in the evidence we feel that this paper may serve as a stepping-stone for future researchers to improve data gathering that targets neurocognitive, neurobehavioural and neuropsychiatric symptoms following a head injury.

  6. Dopamine inhibits lipopolysaccharide-induced nitric oxide production through the formation of dopamine quinone in murine microglia BV-2 cells

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    Yasuhiro Yoshioka


    Full Text Available Dopamine (DA has been suggested to modulate functions of glial cells including microglial cells. To reveal the regulatory role of DA in microglial function, in the present study, we investigated the effect of DA on lipopolysaccharide (LPS-induced nitric oxide (NO production in murine microglial cell line BV-2. Pretreatment with DA for 24 h concentration-dependently attenuated LPS-induced NO production in BV-2 cells. The inhibitory effect of DA on LPS-induced NO production was not inhibited by SCH-23390 and sulpiride, D1-like and D2-like DA receptor antagonists, respectively. In addition, pretreatment with (−-(6aR,12bR-4,6,6a,7,8,12b-Hexahydro-7-methylindolo[4,3-a]phenanthridin (CY 208–243 and bromocriptine, D1-like and D2-like DA receptor agonists, respectively, did not affect the LPS-induced NO production. N-Acetylcysteine, which inhibits DA oxidation, completely inhibited the effect of DA. Tyrosinase, which catalyzes the oxidation of DA to DA quionone (DAQ, accelerated the inhibitory effect of DA on LPS-induced NO production. These results suggest that DA attenuates LPS-induced NO production through the formation of DAQ in BV-2 cells.

  7. Macroprolactinemia and Empty Sella Syndrome. (United States)

    Taieb, Ach; Maha, Kacem Njah; El Abed, Yosra Hasni; Beizig, Amel Maaroufi; Chadli, Molka Chaieb; Ach, Koussay


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

  8. Management of prolactinoma with cabergoline treatment in a pregnant woman during her entire pregnancy

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    Sukhwinder Kaur Bajwa


    Full Text Available Management of prolactinoma in pregnancy is a big challenge for the treating obstetrician as prolactin levels are normally raised in pregnancy and this creates a possibility of missing the diagnosis of prolactinoma. Women with micro adenomas and intrasellar macro adenomas do not require serial magnetic resonance imaging (MRI or visual field testing as required in macro adenomas with extrasellar extension. A strict and vigil monitoring during each trimester for any clinical signs and symptoms related to tumor will suffice for the diagnosis of enlarging prolactinoma and for any active intervention required thereof. Dopamine agonists are the first choice of drugs to treat these tumors during pregnancy. Cabergoline is reported to be more effective and better tolerated as compared to traditional bromocriptine, with minimal risk of spontaneous abortion, congenital malformations or menstrual abnormalities. We are reporting a patient with macro prolactinoma who was treated successfully throughout her pregnancy with cabergoline. We achieved a very good control of prolactinoma without any significant alteration of dose and also without any adverse effects. We convey that cabergoline can be a first choice drug to treat macro prolactinomas in pregnancy also.

  9. Pregnancy and tumor outcomes in infertile women with macroprolactinoma on cabergoline therapy. (United States)

    Rastogi, Ashu; Bhadada, Sanjay K; Bhansali, Anil


    Hyperprolactinemia and prolactinomas cause infertility in significant number of women. But, pregnancy may lead to post-partum remission of hyperprolactinemia. The data on pregnancy and tumor outcome in women with macroprolactinoma conceiving on Cabergoline (CAB) therapy is increasing but still less than with Bromocriptine. We studied the incidence of fetal malformations, hyperprolactinemia and tumor course after gestation in infertile women harboring macroprolactinoma, who conceived on CAB therapy during the year 2005-2015. The cohort was divided into two groups based on the continuation of CAB therapy during gestation (Group A) or not (Group B). Forty-eight pregnancies in 33 women were recorded. CAB was continued throughout gestation in 25 pregnancies (Group A). The incidence of missed abortion (8.3%), still birth (4.2%) and low birth weight (7.7%) were not different in two groups. Neural tube defects were observed in 3 pregnancies (all in Group A). Post-partum, recurrence of hyperprolactinemia was observed in 64.6% and 60.9% (p = 0.8) of women in group A and B, respectively. Cabergoline was restarted after 60% and 60.9% (p = 0.9) pregnancies in the two groups in view of symptomatic hyperprolactinemia and/or persistence of macroadenoma. Post-partum, recurrence of hyperprolactinemia is common in spite of significant tumor reduction in infertile women with macroprolactinoma. Continuation of CAB during gestation does not influence the post-pregnancy recurrence of hyperprolactinemia or tumor remission.

  10. [A case of prolonged paroxysmal sympathetic hyperactivity]. (United States)

    Yamamoto, Akiko; Ide, Shuhei; Iwasaki, Yuji; Kaga, Makiko; Arima, Masataka


    We report the case of a 4-year-old girl who presented with paroxysmal sympathetic hyperactivity (PSH), after developing severe hypoxic-ischemic-encephalopathy because of cardiopulmonary arrest. She showed dramatic paroxysmal sympathetic activity with dystonia. She was treated with wide variety of medications against PSH, which were found to be effective in previous studies. Among them, morphine, bromocriptine, propranolol, and clonidine were effective in reducing the frequency of her attacks while gabapentin, baclofen, dantrolene, and benzodiazepine were ineffective. Though the paroxysms decreased markedly after the treatment, they could not be completely controlled beyond 500 days. Following the treatment, levels of plasma catecholamines and their urinary metabolites decreased to normal during inter- paroxysms. However, once a paroxysm had recurred, these levels were again very high. This case study is considered significant for two rea- sons. One is that PSH among children have been rarely reported, and the other is that this case of prolonged PSH delineated the transition of plasma catecholamines during the treatment. The excitatory: inhibitory ratio (EIR) model proposed by Baguley was considered while dis- cussing drug sensitivity in this case. Accumulation of similar case studies will help establish more effective treatment strategies and elucidate the pathophysiology of PSH.

  11. Prolonged Paroxysmal Sympathetic Storming Associated with Spontaneous Subarachnoid Hemorrhage

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    Yan Liu


    Full Text Available Paroxysmal sympathetic storming (PSS is a rare disorder characterized by acute onset of nonstimulated tachycardia, hypertension, tachypnea, hyperthermia, external posturing, and diaphoresis. It is most frequently associated with severe traumatic brain injuries and has been reported in intracranial tumors, hydrocephalous, severe hypoxic brain injury, and intracerebral hemorrhage. Although excessive release of catecholamine and therefore increased sympathetic activities have been reported in subarachnoid hemorrhage (SAH, there is no descriptive report of PSS primarily caused by spontaneous SAH up to date. Here, we report a case of prolonged PSS in a patient with spontaneous subarachnoid hemorrhage and consequent vasospasm. The sympathetic storming started shortly after patient was rewarmed from hypothermia protocol and symptoms responded to Labetalol, but intermittent recurrence did not resolve until 3 weeks later with treatment involving Midazolam, Fentanyl, Dexmedetomidine, Propofol, Bromocriptine, and minimizing frequency of neurological and vital checks. In conclusion, prolonged sympathetic storming can also be caused by spontaneous SAH. In this case, vasospasm might be a precipitating factor. Paralytics and hypothermia could mask the manifestations of PSS. The treatment of the refractory case will need both timely adjustment of medications and minimization of exogenous stressors or stimuli.

  12. Pharmacotherapy for sleep bruxism. (United States)

    Macedo, Cristiane R; Macedo, Elizeu C; Torloni, Maria R; Silva, Ademir B; Prado, Gilmar F


    Sleep bruxism is an oral activity characterized by involuntary teeth grinding or clenching during sleep. Several forms of treatment have been proposed for this disorder, including behavioural, dental and pharmacological strategies. To evaluate the effectiveness and safety of pharmacological therapy for the treatment of sleep bruxism compared with other drugs, no treatment or placebo. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2014), MEDLINE (1966 to August 2014), EMBASE (1980 to August 2013) and LILACS (1982 to August 2014). We identified additional reports from the reference lists of retrieved reports and from reviews on treatment of sleep bruxism. We applied no language restrictions. We selected randomized controlled trials (RCTs) or quasi-RCTs that compared drugs with other drugs, no treatment or placebo in people with sleep bruxism. Review authors carried out data extraction and quality assessment of the included trials independently and in duplicate. We discussed discrepancies until we reached consensus. We consulted a third review author in cases of persistent disagreement. We contacted authors of primary studies when necessary. We identified 18 potentially relevant RCTs, but only seven met the inclusion criteria. All studies had a small number of participants, ranging from seven to 16 people per study and had a cross-over design. Three studies were of low risk of bias, while four were of uncertain risk. Amitriptyline (three studies), bromocriptine (one study), clonidine (one study), propranolol (one study), levodopa (Prolopa®) (one study) and tryptophan (one study) were compared with placebo. Studies evaluating bromocriptine, clonidine, propranolol and levodopa reported our primary outcome of indices of bruxism motor activity.Results were imprecise and consistent with benefit, no difference or harm. These were the specific findings for each of the drugs according to specific outcomes: 1. Amitriptyline versus placebo

  13. Pharmacological interventions for antisocial personality disorder (United States)

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


    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

  14. Dopamine, T cells and multiple sclerosis (MS). (United States)

    Levite, Mia; Marino, Franca; Cosentino, Marco


    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

  15. Autoradiographic localization of dopamine D2-like receptors in the rabbit pulmonary vascular tree. (United States)

    Kobayashi, Y; Ricci, A; Rossodivita, I; Amenta, F


    In the present study, the pharmacological characteristics and the anatomical localization of dopamine D2-like receptor sites in the extraparenchymal and in the intraparenchymal portion of the rabbit pulmonary artery were investigated using combined radioligand binding and light microscope autoradiography with [3H]-spiroperidol (spiperone) as a ligand. The ligand was bound to sections of the pulmonary artery in a manner consistent with the labelling of dopamine D2-like receptors with an equilibrium dissociation constant (Kd) of about 2.4 +/- 0.07 nmol/l and a maximum density of binding sites of 65 +/- 4.5 fmol/mg tissue. In contrast, binding experiments made with sections of rabbit lung did not allow the evaluation of specific binding. Light microscope autoradiography showed the development of specific silver grains within the tunica adventitia of extraparenchymal branches of rabbit pulmonary artery and of large and, to a lesser extent, of medium-sized intraparenchymal branches of the pulmonary artery. No silver grains were found within small branches of the pulmonary artery or of the pulmonary vein. Development of adventitial silver grains was inhibited by compounds active at dopamine receptors. The greater sensitivity to displacement by domperidone, haloperidol, (-)-sulpiride and bromocriptine than to displacement by N-propyl-norapomorphine, quinpirole or clozapine suggests that the [3H]-spiroperidol binding sites observed in extraparenchymal, large and medium-sized branches of the pulmonary artery belong, probably, to the dopamine D2 receptor subtype. The possible pre-junctional localization of these sites is discussed.

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

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


    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

  17. Effects of pharmacological agents upon a transgenic model of Parkinson's disease in Drosophila melanogaster. (United States)

    Pendleton, Robert G; Parvez, Feroz; Sayed, Marwa; Hillman, Ralph


    The human gene that codes for the protein alpha-synuclein has been transferred into the Drosophila melanogaster genome. The transgenic flies recapitulate some of the essential features of Parkinson's disease. These include the degeneration of certain dopaminergic neurons in the brain accompanied by the appearance of age-dependent abnormalities in locomotor activity. In the present study, we tested the locomotor response of these transgenic flies to prototypes of the major classes of drugs currently used to treat this disorder. A time course study was first conducted to determine when impaired locomotor activity appeared relative to normal "wild-type" flies. A climbing or negative geotaxis assay measuring the ability of the organisms to climb up the walls of a plastic vial was used. Based on the results obtained, normal and transgenic flies were treated with each of the drugs in their food for 13 days and then assayed. The activity of transgenic flies treated with L-DOPA was restored to normal. Similarly, the dopamine agonists pergolide, bromocriptine, and 2,3,4,5-tetrahydro-7,8-dihydroxy- 1-phenyl-1H-3-benzazepine (SK&F 38393) were substantially effective. Atropine, the prototypical muscarinic cholinergic receptor antagonist, was also effective but to a lesser extent than the other antiparkinson compounds. p-Chlorophenylalanine, an inhibitor of serotonin synthesis, was without beneficial effect as was alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase, the rate-limiting step in catecholamine biosynthesis. This behavioral study further demonstrates the utility of this model in studying Parkinson's disease and reinforces the concept that inhibition of the action of alpha-synuclein may be useful in its treatment as may dopamine D(1) receptor agonists.

  18. Peripartum cardiomyopathy: definition, incidence, etiopathogenesis, diagnosis, and management. (United States)

    Garg, Jalaj; Palaniswamy, Chandrasekar; Lanier, Gregg M


    Peripartum cardiomyopathy (PPCM) is a serious pregnancy-associated disorder of unknown etiology. The precise cellular and molecular mechanisms underlying PPCM are unclear. A heightened awareness among health care providers can result in early diagnosis of heart failure in late pregnancy and the early postpartum period. Though the symptoms of dyspnea and fatigue can result from normal physiologic changes during pregnancy, an electrocardiogram and brain natriuretic peptide level should be obtained in these patients, in addition to baseline laboratory tests such as a complete blood count, and basic metabolic and hepatic function panels. If the electrocardiogram and brain natriuretic peptide level are abnormal, an echocardiogram should be obtained. The role of endomyocardial biopsy for the diagnosis of PPCM is controversial. Patients should be started on diuretics if volume overloaded, and beta-blockers (preferably metoprolol) if no contraindications exist; angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be avoided during pregnancy or lactation. There are no standard, universally accepted guidelines for the management of PPCM. Although experimental therapies like bromocriptine, pentoxifylline and immunoglobulins have shown promising results, large double-blind randomized trials are essential to confirm the results of smaller studies. In patients with persistent severe left ventricular (LV) dysfunction, advanced therapies like mechanical circulatory support and heart transplantation should be considered. Owing to recent data demonstrating deterioration of LV systolic function after initial recovery, it is essential to maintain long-term follow up of these patients regardless of initial recovery of LV function. We present a comprehensive review of the literature etiopathogenesis, diagnosis, and management of PPCM.

  19. Effect of plasma prolactin on sweat rate and sweat composition during exercise in men. (United States)

    Boisvert, P; Brisson, G R; Péronnet, F


    We investigated the role of the exercise-induced elevation of plasma prolactin (PRL) concentration on sweat rate and composition during prolonged exercise in men. Two groups of healthy young males (20-26 yr old) showing a high (high responders; n = 8) or a low (low responders; n = 7) response of plasma PRL concentration to exercise were studied during a 60-min period of exercise on a cycle ergometer (65% maximum O2 consumption) in warm conditions (26.2 +/- 0.1 degrees C; 57 +/- 1% relative humidity), 1 h after receiving 1.25 mg bromocriptine (BRC) per os or a placebo. In high responders, administration of BRC totally abolished the threefold increase in plasma PRL observed in response to exercise with placebo [placebo, 10 +/- 2 (rest) and 30 +/- 2 micrograms/l (exercise); BRC, 9 +/- 1 (rest) and 8 +/- 1 microgram/l (exercise)]. The latter was associated with a significant decrease in sweat rate (2.7 +/- 0.5 to 1.9 +/- 0.3 and a significant increase in sweat Na+ concentration (57 +/- 7 to 68 +/- 5 mmol/l). BRC also reduced the small response in plasma PRL concentration observed in low responders [placebo, 10 +/- 1 (rest) and 15 +/- 1 microgram/l (exercise); BRC, 9 +/- 1 (rest) and 7 +/- 1 microgram/l (exercise)], but this was not associated with any change in sweat rate (2.2 +/- 0.2 to 1.9 +/- 0.3 or in sweat Na+ concentration (63 +/- 10 to 64 +/- 9 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Risperidone-Induced Inactivation and Clozapine-Induced Reactivation of Rat Cortical Astrocyte 5-Hydroxytryptamine7 Receptors: Evidence for In Situ G Protein-Coupled Receptor Homodimer Protomer Cross-Talk (United States)

    Smith, Carol; Toohey, Nicole; Knight, Jessica A.; Klein, Michael T.


    We have reported previously novel drug-induced inactivation and reactivation of human 5-hydroxytryptamine7 (5-HT7) receptors in a recombinant cell line. To explain these novel observations, a homodimer structure displaying protomer-protomer cross-talk was proposed. To determine whether these novel observations and interpretations are due to an artifactual G protein-coupled receptor (GPCR) mechanism unique to the recombinant cell line, we explored the properties of r5-HT7 receptors expressed by cortical astrocytes in primary culture. As in the recombinant cell line, risperidone, 9-OH-risperidone, methiothepin, and bromocriptine were found to potently inactivate r5-HT7 receptors. As in the recombinant cell line, exposure of risperidone-inactivated astrocyte r5-HT7 receptors to competitive antagonists resulted in the reactivation of r5-HT7 receptors. The potencies of the reactivating drugs closely correlated with their affinities for h5-HT7 receptors. These results indicate the novel inactivating and reactivating property of drugs is not due to an artifact of the recombinant cell line expressing h5-HT7 receptors but is an intrinsic property of 5-HT7 receptors in vitro and ex vivo. This evidence suggests that a native (nonmutated) GPCR, in its native membrane environment (cortical astrocyte primary culture), can function as a homodimer with protomer-protomer cross-talk. Homodimers may be a common GPCR structure. The experimental design used in our studies can be used to explore the properties of other GPCRs in their native forms in recombinant cells, primary cultures expressing the endogenous GPCRs, and possibly in vivo. The homodimer structure and protomer-protomer cross-talk offer new avenues of research into receptor dysfunction in disease states and the development of novel drugs. PMID:21062995

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

    Directory of Open Access Journals (Sweden)

    Farida Chentli


    Full Text Available 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.

  2. A review of canine pseudocyesis. (United States)

    Gobello, C; de la Sota, R L; Goya, R G


    The purpose of this article is to review the most relevant features of the physiology, clinical signs, diagnosis, treatment and prevention of canine pseudocyesis (PSC). This is a physiological syndrome, characterized by clinical signs such as: nesting, weight gain, mammary enlargement, lactation and maternal behaviour, which appears in non-pregnant bitches at the end of metaoestrus. PSC is a frequent finding in domestic dogs. Although it is generally admitted that prolactin (PRL) plays a central role in the appearance of PSC, its precise aetiophysiology is not completely understood yet. A number of clinical studies suggest that at some point of metaoestrus circulating PRL levels rise in overtly pseudopregnant bitches. Individual differences in sensitivity to PRL as well as the existence of molecular variants of canine PRL with different bioactivity versus immunoreactivity ratios may help clarify the aetiopathology of PSC. Diagnosis of PSC is based on the presence of typical clinical signs in metaoestrous non-pregnant bitches. Considering that PSC is a self limiting physiological state, mild cases usually need no treatment. Discouraging maternal behaviour and sometimes fitting Elizabethan collars to prevent licking of the mammary glands may suffice in these cases. Sex steroids (oestrogens, progestins and androgens) have been traditionally used to treat PSC but the side-effects usually outweigh the benefits of these medications. Inhibition of PRL release by ergot derivatives [bromocriptine (10-100 microg/kg per day for 10-14 days], cabergoline (5 microg/kg per day during 5-10 days), metergoline (0.2 mg/kg per day during 8-10 days) has proved to be effective for the treatment of canine PSC. Although some of these ergot derivatives present some untoward side-effects, they are transient and can usually be managed. Predisposed bitches not intended for breeding should be spayed as ovariectomy is the only permanent preventive measure.

  3. [Cabergoline for inhibition of lactation]. (United States)

    Bravo-Topete, Enrique Gómez; Mendoza-Hernández, Freddy; Cejudo-Alvarez, José; Briones-Garduño, Carlos


    Despite advances in prevention inhibition of lactation, only administration of estrogens or these combined with androgens show variable effectiveness and are indirectly associated with high percentage for lactation rebound, thrombosis, or pulmonary embolism or both of the later during puerperium; in addition, bromocriptine, also used indirectly for inhibition of lactation, is associated with lactation, rebound in 18-40%. Cabergolin is a new ergoline with efficient and durable prolactin reducer effect with fewer adverse effects. Which will the smallest cabergolin dosage be to inhibit lactation? To demonstrate clinical effectiveness with smallest cabergolina dosage in lactation inhibition. We carried on a the Service Clinical test on patients hospitalization with an indication to inhibit lactation as the Hospital of Gynecology and Obstetrics, Infantil Maternal Institute of the State of Mexico (IMIEM). The study was done 80 patients to who we administered oral 0.5 mg cabergoline to 40 patients and another group of 40 whom we administered 1.0 mg of cabergoline orally at random and blinded by means of out-patient consultation. We studied correlation between dose and inhibition of lactation as well as presence of adverse effects. In the group of patients to whom administered 0.5 mg, we found 65% (n = 26) with lactation inhibition; adverse effects in this group appeared in 32.5% (n = 13) the second group with a dose of 1.0 mg; 95% with adverse effects in 25% P < 0.001. Inhibition of lactation with unique dose of 1.0 has satisfactory clinical effectiveness, this being the smaller dose to inhibit lactation at a suitable percentage.

  4. Stimulation of mammogenesis and lactogenesis by recombinant bovine placental lactogen in steroid-primed dairy heifers. (United States)

    Byatt, J C; Eppard, P J; Veenhuizen, J J; Curran, T L; Curran, D F; McGrath, M F; Collier, R J


    A model of induced lactation was modified to examine the effects of bovine prolactin (bPRL) and bovine placental lactogen (bPL) on mammary growth and differentiation. Thirty-two peripubertal, non-pregnant Holstein heifers were given daily s.c. injections of oestradiol (0.05 mg/kg) and progesterone (0.25 mg/kg) for 7 days to initiate mammary growth. Treatment with bromocriptine (40 mg/3 days) reduced serum PRL concentrations to approximately 25% of pretreatment levels, for the duration of the study. On the day following the last steroid injection, groups of eight heifers were given twice daily s.c. injections of either saline (negative control), recombinant bPRL (rbPRL; 80 mg/day) or recombinant bPL (rbPL; 80 and 160 mg/day) for 7 days. At the end of this period (day 15), growth and differentiation of the mammary glands were assessed. Treatment with rbPL increased total mammary DNA above control value by 50 and 60% for the 80 and 160 mg/day doses respectively. However, total DNA was not different for the control and rbPRL-treated groups. The blood serum concentration of alpha-lactalbumin was measured daily throughout the study and used as an index of mammary differentiation. Both rbPRL and rbPL stimulated mammary differentiation (i.e. induction of milk synthesis), although rbPRL appeared to be more potent than rbPL. These results indicate that rbPL is lactogenic in vivo and strongly suggest that bPL is a mammary mitogen.

  5. Suckling-induced prolactin release potentiates mifepristone-induced lactogenesis in pregnant rats. (United States)

    Deis, R P; Carrizo, D G; Jahn, G A


    Suckling, starting at 19:00 h on Day 18 of pregnancy, induced a significant increase in serum prolactin concentration at 20:00 h on Day 19 of pregnancy, but no increase in mammary gland casein or lactose content. Mifepristone (2 mg/kg) injection at 08:00 h on Day 19 of pregnancy induced significant increases in casein, but not in lactose, 24 h after administration. Mifepristone alone did not induce prolactin secretion, indicating that lactogenesis was induced by placental lactogen in the absence of progesterone action. When mifepristone was injected into suckling rats, serum prolactin concentrations were higher than in the untreated suckling rats. Casein in these rats increased significantly 12 h after mifepristone administration and lactose at 24 h after. If the suckling mifepristone-treated rats were given two injections of bromocriptine (1.5 mg/kg) at 12:00 h on Days 18 and 19 of pregnancy, serum prolactin concentrations were not increased by suckling, but casein and lactose concentrations in the mammary gland showed values similar to those obtained in the mifepristone-treated non-suckling rats. Mifepristone can therefore potentiate suckling-induced prolactin release in pregnant rats, demonstrating a direct central inhibitory action of progesterone on prolactin secretion. This suckling-induced prolactin secretion, unable to induce casein or lactose synthesis in the presence of progesterone, enhanced significantly synthesis of these milk components in the absence of progesterone action (rats treated with mifepristone). Fatty acid synthase, which is stimulated by the suckling stimulus in lactating rats, was not modified by mifepristone or suckling in pregnant rats.

  6. Consumption of endophyte-infected fescue seed during the dry period does not decrease milk production in the following lactation. (United States)

    Baldwin, Ransom L; Capuco, Anthony V; Evock-Clover, Christina M; Grossi, Paolo; Choudhary, Ratan K; Vanzant, Eric S; Elsasser, Theodore H; Bertoni, Giuseppe; Trevisi, Erminio; Aiken, Glen E; McLeod, Kyle R


    Ergot alkaloids in endophyte-infected grasses inhibit prolactin (PRL) secretion and may reduce milk production of cows consuming these grasses. We investigated the effects of consuming endophyte-infected fescue seed during late lactation and the dry period on mammary growth, differentiation, and milk production. Twenty-four multiparous Holstein cows were randomly assigned to 3 treatment groups. Starting at 90±4 d prepartum, cows were fed endophyte-free fescue seed (control; CON), endophyte-free fescue seed plus 3×/wk subcutaneous injections of bromocriptine (0.1mg/kg of body weight, positive control; BROMO), or endophyte-infected fescue seed (INF) as 10% of the diet on an as fed basis. Although milk yield of groups did not differ before treatment, at dry off (-60 d prepartum) INF and BROMO cows produced less milk than CON. Throughout the treatment period, basal concentrations of PRL and the prepartum increase in plasma PRL were reduced in INF and BROMO cows compared with CON cows. Three weeks after the end of treatment, circulating concentrations of PRL were equivalent across groups. In the subsequent lactation milk yield was not decreased; in fact, BROMO cows exhibited a 9% increase in milk yield relative to CON. Evaluation of mammary tissue during the dry period and the subsequent lactation, by quantitative histology and immunohistochemical analysis of proliferation markers and putative mammary stem or progenitor cell markers, indicated that feeding endophyte-infected fescue seed did not significantly affect mammary growth and development. Feeding endophyte-infected grasses during the dry period may permit effective utilization of feed resources without compromising milk production in the next lactation. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. Parkinsonism secondary to ethylene oxide exposure

    Directory of Open Access Journals (Sweden)

    Egberto R. Barbosa


    Full Text Available Ethylene oxide is a gas widely used in the production of industrial chemicals. It is also used to sterilize heat-sensitive medical supplies. Previous reports of acute and chronic exposure have described neurotoxic effects like peripheral neuropathy and cognitive impairment. We describe a pure parkinsonian syndrome following acute ethylene oxide intoxication. A 39-years-old male was referred to our Movement Disorders Clinic tor evaluation of a parkinsonian syndrome. He was acutely exposed to ethylene oxide four years before and remained comatose for three days, and gradually regained consciousness.. At that time he showed a global parkinsonian syndrome including bradykinesia, rigidity and rest tremor, with a severe motor disability; no other neurological disorders were found. The symptomatology was partially controlled with biperidene and levodopa plus carbidopa. Two years later he developed L-dopa induced dyskinesias. Four years after the intoxication he was evaluated at our clinic. General examination showed no abnormalities. Neurologic examination revealed a normal menta1 status. Motor evaluation disclosed moderate bradykinesia, rigidity and rest tremor, shuffling gait, poor facial mimic, stooped posture, and his speech was low and monotonous; deep tendon reflexes were brisk. The Hoehn-Yahr disability score was degree IV. Routine laboratory and radiological exams showed results within normal limits. The CSF examination was normal. Brain computed tomography and magnetic ressonance were normal. A trial with bromocriptine and levodopa plus carbidopa did not improve dyskinesia, and he was put on a schedule including amantadine and biperidene with improvement to grade III in Hoehn-Yahr scale. In the present case there was a clear relation between the acute exogenous intoxication and irreversible parkinsonism. No other causes for the condition were identified.

  8. Parkinson's Disease: From Pathogenesis to Pharmacogenomics. (United States)

    Cacabelos, Ramón


    Parkinson's disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer's disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson's disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects. Parkinson's disease neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta, with widespread involvement of other central nervous system (CNS) structures and peripheral tissues. Pathogenic mechanisms associated with genomic, epigenetic and environmental factors lead to conformational changes and deposits of key proteins due to abnormalities in the ubiquitin-proteasome system together with dysregulation of mitochondrial function and oxidative stress. Conventional pharmacological treatments for PD are dopamine precursors (levodopa, l-DOPA, l-3,4 dihidroxifenilalanina), and other symptomatic treatments including dopamine agonists (amantadine, apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine), monoamine oxidase (MAO) inhibitors (selegiline, rasagiline), and catechol-O-methyltransferase (COMT) inhibitors (entacapone, tolcapone). The chronic administration of antiparkinsonian drugs currently induces the "wearing-off phenomenon", with additional psychomotor and autonomic complications. In order to minimize these clinical complications, novel compounds have been developed. Novel drugs and bioproducts for the treatment of PD should address dopaminergic neuroprotection to reduce premature neurodegeneration in addition to enhancing

  9. Hypothalamic, pituitary and thyroid dysfunction after radiotherapy to the head and neck

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    Samaan, N.A.; Vieto, R.; Schultz, P.N.; Maor, M.; Meoz, R.T.; Sampiere, V.A.; Cangir, A.; Ried, H.L.; Jesse, R.H. Jr.


    One hundred-ten patients who had nasopharyngeal cancer and paranasal sinus tumors and were free of the primary disease were studied one to 26 years following radiotherapy. There were 70 males and 40 females ranging in age from 4 to 75 years, with a mean age of 36.5 years. During therapy both the hypothalamus and the anterior pituitary gland were in the field of irradiation. The radiation dose to the hypothalamus and the anterior pituitary gland was estimated to be 400 to 7500 rad with a median dose of 5618 rad to the anterior pituitary gland and a median dose of 5000 rad to the hypothalamus. We found evidence of endocrine deficiencies in 91 of the 110 patients studied. Seventy-six patients showed evidence of one or more hypothalamic lesions and 43 patients showed evidence of primary pituitary deficiency. Forty of the 66 patients who received radiotherapy to the neck for treatment or prevention of lymph node metastasis showed evidence of primary hypothyroidism. The range of the dose to the thyroid area was 3000 to 8800 rad with a median of 5000 rad. One young adult woman who developed galactorrhea and amenorrhea 2 years following radiotherapy showed a high serum prolactin level, but had normal anterior pituitary function and sella turcica. She regained her menses and had a normal pregnancy and delivery following bromocriptine therapy. These results indicate that endocrine deficiencies after radiotherapy for tumors of the head and neck are common and should be detected early and treated. Long-term follow-up of these patients is indicated since complications may appear after the completion of radiotherapy.

  10. Bone metabolism in obese rats programmed by early weaning. (United States)

    de Albuquerque Maia, Lígia; Lisboa, Patrícia Cristina; de Oliveira, Elaine; da Silva Lima, Natália; Lima, Inaya Correa Barbosa; Lopes, Ricardo Tadeu; Ruffoni, Leandro Dias Gonçalves; Nonaka, Keico Okino; de Moura, Egberto Gaspar


    Obesity and osteoporosis seem to have a common pathogenesis, especially because bone and adipose tissue have common origins. Since early weaning (EW) decreases adipogenesis and osteogenesis in neonate, further programming for obesity and hyperleptinemia, we hypothesized that these changes in adipogenesis could affect bone metabolism. Lactating rats were separated into 3 groups: control - dams whose pups ate milk throughout lactation; mechanical EW (MEW) - dams were involved with a bandage interrupting suckling in the last 3days of lactation; pharmacological EW (PEW) - dams were bromocriptine-treated (0.5mg/twice a day via intraperitoneal injection) 3days before weaning. The adult offspring was subjected to dual-energy X-ray absorptiometry and bone tissue was also evaluated by computed tomography, microcomputed tomography and biomechanical tests, beyond serum analyses. MEW and PEW presented higher total bone mineral density (BMD), total bone mineral content, spine BMD and bone area in postnatal day 150 (PN150). In PN180, both groups also presented increase of these parameters and higher femur BMD and fourth lumbar vertebra (LV4) BMD, femoral head radiodensity and LV4 vertebral body radiodensity, trabecular number, stiffness and break load; lower trabecular separation, maximal deformation and break deformation, and also hyperleptinemia and higher visceral fat mass and 25-hydroxivitamin D, whereas parathyroid hormone was unchanged. Serum C-terminal cross-linked telopeptide of type I collagen was lower for both groups. Since both models program for obesity and increased bone mass, and leptin increases plasma vitamin D levels, probably leptin is the link between obesity and higher bone mass. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. [Anxiolytic effects of lisuride and its agonistic action to central 5-HT1A receptors]. (United States)

    Akai, T; Takahashi, M; Nakada, Y; Ohnishi, R; Ikoma, Y; Yamaguchi, M


    Effects of lisuride, a derivative of ergot alkaloid, on central 5-HT1A receptors were investigated biochemically, behaviorally and electroencephalographically (EEG) in rats and rabbits. Effects of lisuride in water-lick conflict tests were also investigated in rats. Lisuride was found to strongly inhibit the bindings of [3H]8-OH-DPAT to 5-HT1A receptors in the raphe nucleus, hippocampus, cortex, amygdala and hypothalamus of rat brain. Inhibitory effects of lisuride on bindings of [3H]8-OH-DPAT in the hippocampus was almost the same as that of 5-HT (Ki = 0.5 nM) and stronger than those of the 5-HT agonist 5-MeO-DMT (Ki = 2.1 nM) or other ergot derivatives (bromocriptine and pergolide, Ki = 3.0 nM). Lisuride (0.1-0.5 mg/kg, i.p.), like 8-OH-DPAT, dose-dependently induced a 5-HT behavioral syndrome in rats. Lisuride affected locomotor activity in rats, whereas 8-OH-DPAT did not. In hippocampal EEG of rabbits, lisuride (0.01-0.03 mg/kg, i.v.), like 8-OH-DPAT and diazepam, dose-dependently inhibited rhythmical slow activity (RSA) induced by acoustical stimulation (3100 Hz) and also inhibited the RSA increased by administration of anxiogenic FG7142. In water-lick conflict tests, lisuride (0.05-0.1 mg/kg, i.p.), like diazepam, increased the number of shocks. These findings indicated that lisuride acts as a strong agonist on central 5-HT1A receptors and suggested that lisuride might be a potential anxiolytic.

  12. [Parkinsonism secondary to ethylene oxide exposure: case report]. (United States)

    Barbosa, E R; Comerlatti, L R; Haddad, M S; Scaff, M


    Ethylene oxide is a gas widely used in the production of industrial chemicals. It is also used to sterilize heat-sensitive medical supplies. Previous reports of acute and chronic exposure have described neurotoxic effects like peripheral neuropathy and cognitive impairment. We describe a pure parkinsonian syndrome following acute ethylene oxide intoxication. A 39-years-old male was referred to our Movement Disorders Clinic for evaluation of a parkinsonian syndrome. He was acutely exposed to ethylene oxide four years before and remained comatose for three days, and gradually regained consciousness. At that time he showed a global parkinsonian syndrome including bradykinesia, rigidity and rest tremor, with a severe motor disability; no other neurological disorders were found. The symptomatology was partially controlled with biperidene and levodopa plus carbidopa. Two years later he developed L-dopa induced dyskinesias. Four years after the intoxication he was evaluated at our clinic. General examination showed no abnormalities. Neurologic examination revealed a normal mental status. Motor evaluation disclosed moderate bradykinesia, rigidity and rest tremor, shuffling gait, poor facial mimic, stooped posture, and his speech was low and monotonous; deep tendon reflexes were brisk. The Hoehn-Yahr disability score was degree IV. Routine laboratory and radiological exams showed results within normal limits. The CSF examination was normal. Brain computed tomography and magnetic ressonance were normal. A trial with bromocriptine and levodopa plus carbidopa did not improve dyskinesia, and he was put on a schedule including amantadine and biperidene with improvement to grade III in Hoehn-Yahr scale. In the present case there was a clear relation between the acute exogenous intoxication and irreversible parkinsonism.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Type 2 Diabetes Mellitus: A Review of Current Trends

    Directory of Open Access Journals (Sweden)

    Abdulfatai B. Olokoba


    Full Text Available Type 2 diabetes mellitus (DM is a chronic metabolic disorder in which prevalence has been increasing steadily all over the world. As a result of this trend, it is fast becoming an epidemic in some countries of the world with the number of people affected expected to double in the next decade due to increase in ageing population, thereby adding to the already existing burden for healthcare providers, especially in poorly developed countries. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include type 2 diabetes mellitus, prevalence, current diagnosis, and current treatment. Only articles in English were included. Screening and diagnosis is still based on World Health Organization (WHO and American Diabetes Association (ADA criteria which include both clinical and laboratory parameters. No cure has yet been found for the disease; however, treatment modalities include lifestyle modifications, treatment of obesity, oral hypoglycemic agents, and insulin sensitizers like metformin, a biguanide that reduces insulin resistance, is still the recommended first line medication especially for obese patients. Other effective medications include non-sulfonylurea secretagogues, thiazolidinediones, alpha glucosidase inhibitors, and insulin. Recent research into the pathophysiology of type 2 DM has led to the introduction of new medications like glucagon-like peptide 1 analogoues: dipeptidyl peptidase-IV inhibitors, inhibitors of the sodium-glucose cotransporter 2 and 11ß-hydroxysteroid dehydrogenase 1, insulin-releasing glucokinase activators and pancreatic-G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, metabolic inhibitors of hepatic glucose output and quick-release bromocriptine. Inhaled insulin was licensed for use in 2006 but has been withdrawn from the market because of low patronage.

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

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


    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.

  15. [Gender effect on cardiomyopathy]. (United States)

    Biagini, Elena; Berardini, Alessandra; Graziosi, Maddalena; Rosmini, Stefania; Pazzi, Chiara; Rapezzi, Claudio


    The role of a gender effect (that means differences in clinical manifestations, access to therapies and response to treatments according to gender) in cardiomyopathies remains a matter of debate. Although recent studies have evaluated the differences in the clinical features and prognosis between the two sexes, many issues remain to be elucidated. At present, the only sex-specific condition that affects females is peripartum cardiomyopathy. Recent evidence suggests a pathogenetic role of a prolactin derivative, and ongoing clinical trials are investigating the possibility of targeted therapies using prolactin secretion inhibitors, such as bromocriptine and carbegoline. Although women were considered so far only carriers of X-linked diseases (Anderson-Fabry disease, Danon disease, Hunter syndrome and dystrophinopathies), clinical experience showed a wide spectrum of clinical manifestations in females due to random X chromosome inactivation. Conversely, in mitochondrial diseases (with matrilineal inheritance), cardiomyopathies may occur in the context of clinical multisystemic involvement without significant gender-related differences. Autosomal inherited cardiomyopathies also show different phenotypes and prognostic impact according to gender. The hypothesis of a premenopausal protective role of female hormones towards myocardial involvement has been raised by recent data on transtiretin-related amyloidosis and hypertrophic cardiomyopathy. Preexisting cardiomyopathies may affect pregnancy, labor and delivery in women, since all these conditions are associated with important hemodynamic changes. Women with low-risk hypertrophic cardiomyopathy (asymptomatic and without left ventricular outflow tract gradient) usually can tolerate pregnancy. Conversely, women who are symptomatic before pregnancy or have severe hypertrophy with important outflow tract gradient are at higher risk and should be referred to a tertiary center to be evaluated on a case by case basis

  16. Gsp mutation in acromegaly and its influence on TRH-induced paradoxical GH response. (United States)

    Goto, Yuko; Kinoshita, Manabu; Oshino, Satoru; Arita, Hideyuki; Kitamura, Tetsuhiro; Otsuki, Michio; Shimomura, Iichiro; Yoshimine, Toshiki; Saitoh, Youichi


    We recently reported that paradoxical GH response to TRH administration reflects biological characteristics in patients with acromegaly. The aim of this study is to elucidate the relationship between gsp mutations and the paradoxical GH response to TRH. Sixty-seven patients with acromegaly were included for analysis. Paradoxical increase in serum GH level to TRH, GH suppression by octreotide and bromocriptine, radiological profiles and histopathological findings were analysed with respect to tumour gsp-mutation status. Twenty-six (38·8%) gsp mutations were detected, and the number of paradoxical GH responders to TRH, defined as an increase of 100% or more in GH after TRH, was 49 (73·1%). Among the paradoxical GH responders to TRH, 21 patients (42·9%) had a gsp mutation and 28 patients (57·1%) did not. The percentage of paradoxical GH responders to TRH in gsp-positive and gsp-negative patients was not significantly different (80·8% and 68·3%, respectively). The gsp-positive group showed a significantly higher paradoxical increase in serum GH level by TRH administration (1830% vs 650% GH increase, P = 0·045) and greater GH suppression by octreotide (88·7% vs 75·4% GH decrease, P = 0·003) than the gsp-negative group. Paradoxical GH response to TRH was observed regardless of gsp mutation, although the rate of increase was significantly higher in gsp-positive patients. These results suggest that gsp mutation is not sufficient to cause the paradoxical GH response to TRH, while other unidentified factors have a strong influence on paradoxical GH response to TRH in patients with acromegaly. © 2013 John Wiley & Sons Ltd.

  17. Comparative tolerability of the newer generation antiparkinsonian agents. (United States)

    Lambert, D; Waters, C H


    In recent years, the treatment of Parkinson's disease has undergone an immense amount of research, resulting in the development of multiple new medications. This has largely been fuelled by dissatisfaction over the development of motor complications secondary to long term levodopa therapy. Different treatment approaches are applied depending on the stage of Parkinson's disease. In early and mild Parkinson's disease, selegiline offers a limited symptomatic effect. Its neuroprotective effect, although at present theoretical, has questionable clinical relevance. Increased mortality associated with selegiline has been reported, although a meta-analysis of 5 different trials did not support this finding. The newer, non-ergoline dopamine agonists, pramipexole and ropinirole, have undergone extensive studies to evaluate their efficacy as monotherapy in early Parkinson's disease. These newer agonists are ideal initial symptomatic medications, primarily because they delay the onset of levodopa-induced motor fluctuations. Efficacy of the newer dopamine agonists in advanced disease seems to be comparable to that of the older agents, bromocriptine and pergolide. Adverse effects can be reduced by starting the medication at a very low dose and then slowly titrating upward. Catechol-O-methyl transferase (COMT) inhibitors are indicated for the treatment of motor fluctuations in advanced disease, particularly the 'wearing-off' phenomenon. Tolcapone, a peripheral and central COMT inhibitor, appears to be quite effective, producing a 47% reduction in 'off' time. Unfortunately, 3 deaths have been observed, which are presumably secondary to tolcapone therapy. The drug has been withdrawn in many countries, and liver enzyme testing is mandatory in the US. Entacapone, a purely peripheral COMT inhibitor with a lower potency than tolcapone, has also proved to be effective and has not been associated with liver damage, obviating the need for testing.

  18. Evidence-based guideline: treatment of tardive syndromes: report of the Guideline Development Subcommittee of the American Academy of Neurology. (United States)

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


    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).

  19. Diagnostic challenges and management of a patient with acromegaly due to ectopic growth hormone-releasing hormone secretion from a bronchial carcinoid tumour

    Directory of Open Access Journals (Sweden)

    Nikolaos Kyriakakis


    Full Text Available A male patient presented at the age of 30 with classic clinical features of acromegaly and was found to have elevated growth hormone levels, not suppressing during an oral glucose tolerance test. His acromegaly was originally considered to be of pituitary origin, based on a CT scan, which was interpreted as showing a pituitary macroadenoma. Despite two trans-sphenoidal surgeries, cranial radiotherapy and periods of treatment with bromocriptine and octreotide, his acromegaly remained active clinically and biochemically. A lung mass was discovered incidentally on a chest X-ray performed as part of a routine pre-assessment for spinal surgery 5 years following the initial presentation. This was confirmed to be a bronchial carcinoid tumour, which was strongly positive for growth hormone-releasing hormone (GHRH and somatostatin receptor type 2 by immunohistochemistry. The re-examination of the pituitary specimens asserted the diagnosis of pituitary GH hyperplasia. Complete resolution of the patient’s acromegaly was achieved following right lower and middle lobectomy. Seventeen years following the successful resection of the bronchial carcinoid tumour the patient remains under annual endocrine follow-up for monitoring of the hypopituitarism he developed after the original interventions to his pituitary gland, while there has been no evidence of active acromegaly or recurrence of the carcinoid tumour. Ectopic acromegaly is extremely rare, accounting for <1% of all cases of acromegaly. Our case highlights the diagnostic challenges differentiating between ectopic acromegaly and acromegaly of pituitary origin and emphasises the importance of avoiding unnecessary pituitary surgery and radiotherapy. The role of laboratory investigations, imaging and histology as diagnostic tools is discussed.

  20. Cabergoline effect on blood sugar in type 2 diabetic patients with oral agent failure. (United States)

    Taghavi, Seyyed Morteza; Fatemi, Seyyede Sedighe; Rokni, Hale


    Ergot-derived dopamine D2 receptor agonists are the usual treatment of hyperprolactinemia and Parkinson's disease and recently bromocriptine has been approved for the treatment of type 2 diabetes. The aim of this study was the evaluation of short-term effect of cabergoline in poorly controlled diabetic patients with oral agent failure who refused insulin therapy. This study was performed in 17 overweight women and men with type 2 diabetes with persistent hyperglycemia in spite of treatment with maximum dose of sulfonylurea, metformin and pioglitazone. 10 patients (group I) randomized to be treated with cabergoline 0.5 mg weekly for 3 months and 7 patients (group II) with placebo. Fasting and postprandial plasma glucose concentration and HbAlc measured in beginning and end of the study. FBS decreased from 210.70 +/- 21.29 to 144.90 +/- 26.56 mg/dl in cabergoline group whereas it decreased in placebo group insignificantly. Postprandial blood glucose decreased from 264.2 +/- 28 mg/dl to 203.6 +/- 34.34 mg/dl in cabergoline group whereas it increased in placebo group insignificantly. HbA1c decreased in cabergoline group from 8.48 +/- 0.44 to 7.7 +/- 0.11 whereas in control group it increased insignificantly from 8.7 +/- 0.33 to 8.8 +/- 0.16. Cabergoline improves glycemic control in type 2 diabetic patients with oral agent failure. It reduces both fasting and postprandial plasma glucose levels and causes 0.45-1.11 reduction in HbA1c.

  1. Parkinson’s Disease: From Pathogenesis to Pharmacogenomics

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    Ramón Cacabelos


    Full Text Available Parkinson’s disease (PD is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer’s disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson’s disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects. Parkinson’s disease neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta, with widespread involvement of other central nervous system (CNS structures and peripheral tissues. Pathogenic mechanisms associated with genomic, epigenetic and environmental factors lead to conformational changes and deposits of key proteins due to abnormalities in the ubiquitin–proteasome system together with dysregulation of mitochondrial function and oxidative stress. Conventional pharmacological treatments for PD are dopamine precursors (levodopa, l-DOPA, l-3,4 dihidroxifenilalanina, and other symptomatic treatments including dopamine agonists (amantadine, apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine, monoamine oxidase (MAO inhibitors (selegiline, rasagiline, and catechol-O-methyltransferase (COMT inhibitors (entacapone, tolcapone. The chronic administration of antiparkinsonian drugs currently induces the “wearing-off phenomenon”, with additional psychomotor and autonomic complications. In order to minimize these clinical complications, novel compounds have been developed. Novel drugs and bioproducts for the treatment of PD should address dopaminergic neuroprotection to reduce premature neurodegeneration in

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

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    Thanos, P.K.; Wang, G.; Thanos, P.K..; Kim, R.; Cho, J.; Michaelides, M.; Anderson, B.J.; Primeaux, S.D.; Bray, G.A.; Wang, G.-J.; Robinson, J.K.; Volkow, N.D.


    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, we 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.

  3. Role of dopamine receptor agonists in the treatment of early Parkinson's disease. (United States)

    Bonuccelli, Ubaldo; Del Dotto, Paolo; Rascol, Olivier


    In the last two decades, the usefulness of dopamine receptor agonists in the symptomatic treatment of Parkinson' disease (PD) has been demonstrated in many randomized controlled clinical trials. The initial role of such compounds as an adjunctive therapy to L-dopa to improve motor fluctuations has now expanded to the treatment of early PD as initial monotherapy. The rationale for the use of dopamine receptor agonists in early disease is to delay or reduce the incidence of motor complications resulting from long-term L-dopa therapy, probably by virtue of less pulsatile stimulation of postsynaptic dopamine receptors. Indeed, controlled trials with both ergot and non-ergot dopamine receptor agonists, such as cabergoline, pergolide, pramipexole and ropinirole, have shown lower risk of motor fluctuations and dyskinesias than with L-dopa, when used as monotherapy in early PD patients. The benefit of agonists in preventing motor complications is, however, balanced by a smaller effect on motor symptoms compared with L-dopa. Moreover, a greater incidence of side-effects, particularly somnolence, hallucinations and leg oedema, occurs with dopamine receptor agonists. Because of the risk of fibrotic reactions, ergot derivatives (bromocriptine, cabergoline, and pergolide) are not recommended as first-line antiparkinsonian medication. In younger patients, who are usually more prone to developing L-dopa-induced motor complications, the initial treatment with dopamine receptor agonists can be recommended. Further pharmacological refinement of PD management with these drugs may result from new formulations of old drugs, such as once-daily prolonged-release ropinirole, or new agonists, such as the rotigotine patch, that can allow more continuous dopaminergic stimulation and improve patient compliance with the drug treatment. Theoretically, another advantage of dopamine receptor agonists is the potential for a neuroprotective effect, through many different mechanisms of actions

  4. Variation among species in the endocrine control of mammary growth and function: the roles of prolactin, growth hormone, and placental lactogen. (United States)

    Forsyth, I A


    secretion of lactogenic hormones to bring about mammary development. A surge of prolactin secretion occurs at parturition but may not be essential in the initiation of lactation. The timing of progesterone withdrawal correlates well with lactogenesis in eutherian mammals, but species differ in the mechanisms at parturition which bring this about. Marsupials show a quite different pattern of suckling-induced lactation. In maintaining lactation the greatest contrast is between ruminants, in which growth hormone is of particular importance, and other mammals, in which reduction of prolactin secretion with bromocriptine rapidly suppresses milk synthesis and secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

  5. Prospective study to evaluate the association between systemic sclerosis and occupational exposure and review of the literature. (United States)

    Marie, I; Gehanno, J-F; Bubenheim, M; Duval-Modeste, A-B; Joly, P; Dominique, S; Bravard, P; Noël, D; Cailleux, A-F; Weber, J; Lagoutte, P; Benichou, J; Levesque, H


    Systemic sclerosis (SSc) has complex pathogenesis and likely multifactorial causes. Environmental exposures have been suggested to play a role in SSc pathogenesis, including occupational exposure to pollutants and chemicals as well as use of drugs leading to modulation of immune response. Thus, this case-control study aimed to assess: the relationship between SSc and occupational exposure; and the risk of SSc related to occupational exposure in male and female patients. From 2005 to 2008, 100 patients with a definite diagnosis of SSc were included in the study; 3 age, gender, and smoking habits matched controls were selected for each patient. A committee of experts evaluated blindly occupational exposure to crystalline silica, white spirit, organic solvents, ketones, welding fumes, epoxy resins, and pesticides; an occupational exposure score was calculated for all subjects. Our findings were compared with previous data in the literature. Increased ORs for SSc were found for: crystalline silica (pwelding fumes (p=0.021). Elevated risk associated with high final cumulative score in SSc was observed for: crystalline silica, white spirit, chlorinated solvents, trichlorethylene, aromatic solvents, any type of solvents, ketones and welding fumes. A marked association between SSc and occupational exposure was further found for: 1) crystalline silica, chlorinated solvents, trichloroethylene, white spirit, ketones and welding fumes in male patients; and 2) white spirit, aromatic solvents, any type of solvent and ketones in female patients. Finally, we did not find an association between SSc and: 1) the use of drugs that have been speculated to play a role in SSc onset (anorexigens, pentazocine, bromocriptine, l-tryptophan); 2) implants - that are prosthesis, silicone implants, and contact lenses; and 3) dyeing hair. In the literature, SSc has been associated with occupational exposure to silica and solvents, while the association between SSc and specific organic solvents

  6. Metastatic prolactinoma: case report with immunohistochemical assessment for p53 and Ki-67 antigens Prolactinoma metastático: relato de caso com avaliação imuno-histoquímica para os antígenos p53 e Ki-67

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    Paulo S. Crusius


    Full Text Available Pituitary carcinomas are rare neoplasms characterized by craniospinal and/or systemic metastases originated from the pituitary. Their histopathology is frequently indistinguishable from that of benign adenomas. The development of markers that better reflect their behavior is desirable. We present the case of a 47 year-old man with a prolactin-secreting macroadenoma who was submitted to surgeries, cranial radiation therapy, and bromocriptine treatment, but evolved to a fatal outcome after the disclosure of intracranial metastases. Tumor samples underwent p53 and Ki-67 immunohistochemical assessment. p53 was absent in all samples, a rare finding among pituitary carcinomas. Ki-67 proliferative index was 2.80% in the original tumor, 4.40% in the relapse, and 4.45% in the metastasis. The figure in the relapse is higher than the expected for a noninvasive adenoma. In conclusion, p53 staining is not positive in all pituitary carcinomas. A high Ki-67 proliferative index in a pituitary adenoma might indicate a more aggressive behavior.Carcinomas pituitários são neoplasias raras caracterizadas pela presença de metástases cranio-espinhais e/ou sistêmicas originadas da hipófise. Sua histopatologia é freqüentemente indistinguível daquela dos adenomas benignos. O desenvolvimento de marcadores que melhor reflitam o seu comportamento é desejável. Apresentamos o caso de um homem de 47 anos com um macroadenoma secretor de prolactina que foi submetido a procedimentos cirúrgicos, radioterapia e tratamento com bromocriptina, mas que evoluiu para o óbito após o descobrimento de metástases intracranianas. Amostras do tumor foram submetidas à análise imuno-histoquímica para os antígenos p53 e Ki-67. A coloração para p53 foi negativa em todas as amostras, um achado raro entre os carcinomas pituitários. O índice proliferativo Ki-67 foi 2,80% no tumor original, 4,40% na recidiva e 4,45% na metástase. O valor obtido na recidiva é maior que o

  7. [Therapeutic measures in tardive dyskinesia]. (United States)

    Tegeler, J; Wöller, W


    Studies on the treatments for neuroleptic-induced tardive dyskinesia published in the literature are reviewed. The great number of different treatments and the controversial results of most studies show that there is as yet no specific and safe treatment for tardive dyskinesia. Suggestions for well-designed treatment studies are given: Placebo-controlled double-blind design, larger patient populations, clear diagnostic and standard observing and rating conditions using different assessment methods and videotapes, withdrawal of neuroleptics and antiparkinsonian drugs to discover reversible tardive dyskinesia. If this procedure is not feasible, neuroleptics and other drugs should be maintained at a stable dose level. Longer term studies of some months are necessary to study the prolonged efficacy of different drugs. The effect of dopamine-antagonists such as neuroleptics and of dopamine-depleting agents such as reserpine and oxypertine is of limited duration. Dopamine-agonists such as L-Dopa, bromocriptine and amantadine help only few patients and may even aggravate the symptoms of tardive dyskinesia. In some double-blind studies cholinergic drugs such as lecithin and deanol have improved tardive dyskinesia, but further controlled studies are needed. Anticholinergic drugs such as antiparkinsonian agents should not be prescribed because they may aggravate tardive dyskinesia. Some patients respond to GABA-ergic agents such as baclofen, sodium valproate and the benzodiazepines, but further studies are needed before the value of GABA-ergic agents in the treatment of tardive dyskinesia can be properly assessed. After withdrawal of neuroleptics the average of remission rates within a year is 20%-30%. Elderly patients are more likely to have persistent dyskinesias. A progressive stepwise diminution of the neuroleptic dose and of the antiparkinsonian agents is recommended. When a patient's psychosis is exacerbated after withdrawal of the neuroleptics and tardive dyskinesia

  8. In vivo study of prolactin (PRL) intracellular signalling during lactogenesis in the rat: JAK/STAT pathway is activated by PRL in the mammary gland but not in the liver. (United States)

    Jahn, G A; Daniel, N; Jolivet, G; Belair, L; Bole-Feysot, C; Kelly, P A; Djiane, J


    The rat prolactin receptor (PRL-R) exists in two forms, which differ in the length of the cytoplasmic domains, tissue distribution, and biological activity. The short form predominates in liver while the long form is prevalent in mammary gland. We have compared activation by PRL of the JAK2-STAT pathway (protein tyrosine phosphorylation and STAT5 activation) in mammary gland and liver in an in vivo rat model of induction of lactogenesis by PRL injections, and we have studied the relative proportion of both forms of the receptor in these tissues by reverse transcription-polymerase chain reaction. Rats were ovario-hysterectomized on Day 19 of pregnancy, treated with bromocriptine, subsequently injected with 250 micrograms ovine PRL i.p. on Day 20, and killed 0-12 h after. Western blots of solubilized mammary gland and liver membranes immunoprecipitated with anti-PRL-R or anti-JAK2 antibodies showed that the PRL-R is constitutively associated with JAK2 and that the long form of the PRL-R is present in both tissues, while the short form was detected only in liver. Phosphorylated proteins corresponding to the long form of PRL-R and JAK2 appeared 15-60 min after ovine PRL injection in mammary extracts but not in liver. At these same times, an electrophoretic mobility shift assay, using a rat beta-casein probe specific for STAT5 binding, showed activated STAT5 in mammary gland cytosol and nuclear extracts. In the liver, low levels of activated STAT5 were detected in non-treated animals, which were not modified by PRL. Quantitative RT-PCR of liver and mammary PRL-R mRNA showed that the amount of the long form of PRL-R mRNA is roughly comparable in both tissues, while the short form is predominant in liver and in a minority in mammary tissue. Both forms were down-regulated by PRL only in mammary glands. Thus, during lactogenesis, mammary tissue responds to PRL by activation of JAK2 and STAT5, while the liver does not respond to PRL in spite of the presence of PRL

  9. [Oral contraception: users' questions]. (United States)

    Prolongeau, J F


    Answers are provided to common questions about the safety and use of oral contraceptives (OCs). Amenorrhea during OC use has no pathologic significance. It is related to endometrial atrophy resulting from insufficient estrogen after longterm pill use. A formulation with a higher estrogen content may be used for one or two cycles to regenerate the endometrium. If amenorrhea persists for more than a few months after discontinuation of pills, pituitary adenoma should be ruled out. Bromocriptine may be indicated in cases of moderate hyperprolactinemia if pregnancy is desired. All intermenstrual bleeding in pill users should be investigated for organic cause. Once endometrial polyps and other pathologies are ruled out, the cause may be assumed to be functional metrorrhagia due to endometrial atrophy identical to that causing amenorrhea in OC users. Intermenstrual bleeding may occasionally result from interactions with specific classes of drugs. Minor bleeding in the first cycles of pill use is common and usually temporary. Accidentally taking two pills in one day is without consequence. If the interval between pill cycles exceeds one week, there is risk of follicular maturation and a different contraceptive method should be used until the next cycle. Forgetting a combined pill is without consequence for delays of under twelve hours. Another method should be used until the next cycle if two pills are forgotten. Low-dose oral progestins rapidly lose efficacy if not taken at the same time every day. "Morning-after" pills may be used up to 72 hours after unprotected intercourse. The current generation of OCs entails no teratogenic risks. The cause of any pill failure should be sought. There is no increased risk of multiple pregnancy after discontinuation of pills, and fecundity does not decline after longterm pill use. OCs should be avoided by users of some antiepileptic drugs or of drugs that increase hepatic toxicity or act as enzyme inductors. All conditions accompanied

  10. Long-term results of radiotherapy for pituitary adenomas. Evaluation of tumor control and hypopituitarism after radiotherapy

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    Tsuchida, Emiko; Sakai, Kunio; Matsumoto, Yasuo; Sugita, Tadashi; Sasamoto, Ryuta [Niigata Univ. (Japan). School of Medicine


    To evaluate the results of conventional radiotherapy for pituitary adenomas assessed with computed tomography (CT) or magnetic resonance imaging (MRI). Endpoints include tumor control, normalization of hormone levels in functioning adenomas, and hypopituitarism after radiotherapy as an adverse effect. Forty-two patients were treated with radiotherapy from 1982 to 1995 at Niigata University Hospital. Forty patients were irradiated after surgery because of residual adenomas in 33 patients and tumor regrowth in 7 patients. One patient was treated with radiotherapy alone, and the remaining 1 patient was treated with preoperative radiotherapy. Tumor size and extension were evaluated using CT or MRI, and all tumors were macroadenomas. They consisted of 18 non-functioning and 24 functioning adenomas (growth hormone (GH)-secreting: 11, prolactinomas: 7, concomitant GH and prolactin (PRL)-secreting: 5, gonadotropin-secreting: 1). Treatment was given in 200 cGy daily fraction size and a total dose of 50 Gy was given to most patients. Sixteen patients with GH- and/or PRL-secreting adenomas received bromocriptine. Tumor progression was determined by increase in tumor size as shown by CT or MRI. Hypopituitarism after radiotherapy was evaluated using the functions of corticotropin (ACTH), thyrotropin (TSH), and gonadotropin. Median follow-up time from the end of radiotherapy was 103 months. Tumor progression occurred in 2 out of 42 patients and 10-year progression-free rate for all patients was 93.7%. Normalization of GH levels was obtained in 12 of 16 GH-secreting adenomas with a mean time of 27 months after radiotherapy, and 9 of 12 PRL-secreting adenomas achieved normalization of PRL levels with a mean time of 34 months. One gonadotropin-secreting adenoma achieved normalization of gonadotropin level at 21 months after radiotherapy. The incidence of hypopituitarism after radiotherapy increased with time, and cumulative risk of deficiencies of ACTH, TSH, and gonadotropin at 10

  11. Pregnancy rate of gonadotrophin therapy and laparoscopic ovarian electrocautery in polycystic ovary syndrome resistant to clomiphene citrate: a comparative study

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    Ghafarnegad M


    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Polycystic ovary syndrome (PCOS is a common cause of ovulation insufficiency and then infertility. Therapeutic options to induce ovulation in anovulatory PCOS patients are clomiphene citrate, metformin, tamoxifen, dopamine agonists (bromocriptin, Gonadotrophin and laparoscopic ovarian electrocautery (LOE. Gonadotrophin and LOE are important options in anovulatory clomiphene citrate-resistant patients with PCOS. Literature data regarding compare of the efficacy of these two treatments are few. Therefore we aimed to study the pregnancy rates of these treatments in infertile clomiphene citrate-resistant patients with PCOS."n"nMethods: A randomized clinical trial study was carried out in infertile clomiphene citrate-resistant patients with PCOS, referred to infertility clinic of Mirza Koochackhan Hospital of Tehran University of Medical Science in Tehran, Iran, between 2003 and 2008."n"nResults: A total of 100 patients women were randomly allocated in two groups. There were no differences in age and pimary and secondary infertility duration. In LOE treatment group, eight cases (16% were pregnant and all delivered at term. in gonadotrophin treatment 14 cases (28% were pregnant, 10 cases (20% delivered at term

  12. New insights into the importance of prolactin in dairy ruminants. (United States)

    Lacasse, P; Ollier, S; Lollivier, V; Boutinaud, M


    In most mammals, prolactin (PRL) is essential for maintaining lactation, and the suppression of PRL inhibits lactation. However, the involvement of PRL in the control of ruminant lactation is less clear, because inconsistent effects on milk yield have been observed with the short-term suppression of PRL by bromocriptine. Therefore, several experiments have been conducted to assess the galactopoietic role of PRL. In an initial experiment, cows in early lactation received daily injections of the dopamine agonist quinagolide for 9 wk. Quinagolide reduced milking-induced PRL release and caused a faster decline in milk production. Quinagolide also reduced mammary epithelial cell activity, survival, and proliferation. In goats, cabergoline, another dopamine agonist, caused a 28% decrease in milk yield the day after injection. In another experiment, cows were injected for 5d with quinagolide, with quinagolide plus bovine PRL injected at milking time, or with vehicles only. Again, quinagolide reduced milk, protein, and lactose yields. Although PRL injections were not sufficient to restore milk yield, they tended to increase milk protein and lactose yields and increased the viability of mammary epithelial cells purified from milk. Recently, our team stimulated PRL secretion with daily injections of the dopamine antagonist domperidone for 5 wk. Milk production increased gradually and was greater in domperidone-treated cows during the last 4 wk of the treatment period. In most experiments where PRL secretion was manipulated, feed intake paralleled the changes of PRL concentration, supporting the idea that PRL increases feed intake to provide the nutrients necessary to support lactation in dairy ruminants. In late-lactation cows, quinagolide and cabergoline decreased milk production within the first day of treatment and induced more rapid changes in several markers of mammary gland involution after drying-off. In addition, quinagolide improved the resistance to intramammary

  13. 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. (United States)

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


    , 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.

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

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    Mirza MU


    Full Text Available Muhammad Usman Mirza,1 A Hammad Mirza,2 Noor-Ul-Huda Ghori,3 Saba Ferdous4 1Centre for Research in Molecular Medicine, The University of Lahore, Lahore, Pakistan; 2Department of Bioscience, COMSATS Institute of Information Technology, Sahiwal, Pakistan; 3Atta-ur-Rehman School of Applied Biosciences, National University of Science and Technology, Islamabad, Pakistan; 4Institute of Structural and Molecular Biology, University College London, UK Abstract: 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

  15. Dopamine and T cells: dopamine receptors and potent effects on T cells, dopamine production in T cells, and abnormalities in the dopaminergic system in T cells in autoimmune, neurological and psychiatric diseases. (United States)

    Levite, M


    expression and/or responses to dopamine or production of dopamine, (xiii) drugs that affect the dopaminergic system have potent effects on T cells (e.g. dopamine=Intropin, L-dopa, bromocriptine, haloperidol, quinpirole, reserpine, pergolide, ecopipam, pimozide, amantadine, tetrabenazine, nomifensine, butaclamol). Dopamine-induced activation of resting Teffs and suppression of Tregs seem beneficial for health and may also be used for immunotherapy of cancer and infectious diseases. Independently, suppression of DRs in autoimmune and pro-inflammatory T cells, and also in cancerous T cells, may be advantageous. The review is relevant to Immunologists, Neurologists, Neuroimmunologists, Hematologists, Psychiatrists, Psychologists and Pharmacologists. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.


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    N. T. Vatutin


    mechanisms of this cardiomyopathy, the information about pharmacological drugs directed to correction of possible links of development mechanism of this pathology is introduced. On the basis of analyzed data authors discuss relevance, indications and side effects of immunosuppressive therapy, immunoglobulin, pentoxifylline, and prolactin secretion inhibitors — bromocriptine and cabergoline. The experience of cardiac transplantation is specified in patients with refractory peripartum cardiomyopathy, and issues of delivery are highlighted in women suffering from this disease.   

  17. Pramipexole. A review of its use in the management of early and advanced Parkinson's disease. (United States)

    Dooley, M; Markham, A


    Pramipexole is an orally active non-ergoline dopamine agonist with selective activity at dopamine receptors belonging to the D2 receptor subfamily (D2, D3, D4 receptor subtypes) and with preferential affinity for the D3 receptor subtype. It is approved as monotherapy in early Parkinson's disease and as adjunctive therapy to levodopa in patients with advanced disease experiencing motor effects because of diminished response to levodopa. The potential neuroprotective effects of pramipexole have been shown in animal and in vitro studies. Data from relatively long term (10- or 31-week) studies suggest that pramipexole monotherapy (0.375 to 6.0 mg/day) can improve activities of daily living and motor symptoms in patients with early Parkinson's disease. Pramipexole (0.375 to 4.5 mg/day for 31 or 36 weeks), as an adjunct to levodopa in advanced disease, improved activities of daily living and motor symptoms, reduced the duration and severity of 'off' periods and allowed a reduction in levodopa dosage. Mentation, behaviour and mood [Unified Parkinson's Disease Rating Scale (UPDRS) part I], and timed walking test were not significantly improved. The extent of disability improved according to the UPDRS parts II and III but, when assessed by secondary efficacy parameters, it is unclear whether disability or the severity of disease improved. No significant differences were observed in patients randomised to pramipexole or bromocriptine according to a secondary hypothesis in a prospective study in which both drugs were better than placebo. Some quality-of-life measures improved with active treatment relative to placebo. Further studies comparing pramipexole with other dopamine agonists and levodopa in patients with early and advanced Parkinson's disease would be useful. In pramipexole recipients with early disease, the most commonly experienced adverse events were nausea, dizziness, somnolence, insomnia, constipation, asthenia and hallucinations. The most commonly reported

  18. Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease. (United States)

    Deleu, Dirk; Northway, Margaret G; Hanssens, Yolande


    Current research in Parkinson's disease (PD) focuses on symptomatic therapy and neuroprotective interventions. Drugs that have been used for symptomatic therapy are levodopa, usually combined with a peripheral decarboxylase inhibitor, synthetic dopamine receptor agonists, centrally-acting antimuscarinic drugs, amantadine, monoamine oxidase-B (MAO-B) inhibitors and catechol-O-methyltransferase (COMT) inhibitors. Drugs for which there is at least some evidence for neuroprotective effect are certain dopamine agonists, amantadine and MAO-B inhibitors (selegiline). Levodopa remains the most effective drug for the treatment of PD. Several factors contribute to the complex clinical pharmacokinetics of levodopa: erratic absorption, short half-life, peripheral O-methylation and facilitated transport across the blood-brain barrier. In patients with response fluctuations to levodopa, the concentration-effect curve becomes steeper and shifts to the right compared with patients with stable response. Pharmacokinetic-pharmacodynamic modelling can affect decisions regarding therapeutic strategies. The dopamine agonists include ergot derivatives (bromocriptine, pergolide, lisuride and cabergoline), non-ergoline derivatives (pramipexole, ropinirole and piribedil) and apomorphine. Most dopamine agonists have their specific pharmacological profile. They are used in monotherapy and as an adjunct to levodopa in early and advanced PD. Few pharmacokinetic and pharmacodynamic data are available regarding centrally acting antimuscarinic drugs. They are characterised by rapid absorption after oral intake, large volume of distribution and low clearance relative to hepatic blood flow, with extensive metabolism. The mechanism of action of amantadine remains elusive. It is well absorbed and widely distributed. Since elimination is primarily by renal clearance, accumulation of the drug can occur in patients with renal dysfunction and dosage reduction must be envisaged. The COMT inhibitors

  19. Statistical investigation of simulated fed intestinal media composition on the equilibrium solubility of oral drugs. (United States)

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


    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

  20. Valvulopatía cardiaca asociada al uso de agonistas dopaminérgicos en pacientes con hiperprolactinemia Valvular heart disease associated with use of dopaminergic agonists in patients with hyperprolactinemia

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    Yamilé Alvarez Delgado


    Full Text Available La cabergolina y la bromocriptina son fármacos agonistas dopaminérgicos utilizados para tratar la hiperprolactinemia, así como la enfermedad de Parkinson. Entre sus efectos adversos considerados como "muy raros" se ha descrito la capacidad de inducir cambios fibróticos en el aparato valvular cardiaco, inicialmente descritos en pacientes con enfermedad de Parkinson, en quienes se emplean dosis superiores a las que de manera habitual se emplean en el tratamiento de la hiperprolactinemia. Varios estudios han señalado la evidencia de estos hechos y de los posibles mecanismos por los cuales la afectación valvular ocurre. Existen hasta el momento pocas investigaciones sobre el asunto en pacientes con hiperprolactinemia, pero la mayoría de ellos indican que su empleo en este tipo de pacientes no produce afectación valvular clínicamente relevante, hecho que pudiera estar en relación con las dosis empleadas (como promedio 10 veces inferiores a las usadas en la enfermedad de Parkinson; sin embargo, se han detectado algunas anomalías subclínicas en el aparato valvular. Dado lo novedoso del tema y la poca evidencia de estos hechos en pacientes tratadas por hiperprolactinemia se ofreció una amplia revisión sobre el tema.Cabergoline and bromocriptine are dopaminergic agonists drugs used in hyperprolactinemia treatment, as well as in patients with Parkinson's disease. Among its adverse effects considered as "very inusual" is included the ability to induce fibrotic changes in cardiac valvular tract first described in patients with Parkinson disease using doses higher than those usually used in hyperprolactinemia treatment. Some studies have mentioned the evidence on these facts and of the possible mechanisms causing the valvular affection. Until now, there are not much researches on this subject in patients with hyperprolactinemia, but most indicated that its use in this kind of patient can not to produce a clinically relevant valvular afection

  1. Evaluaton of therapy with cabergoline in men with macroprolactinoa. (United States)

    Andrysiak-Mamos, Elzbieta; Kaźmierczyk-Puchalska, Agnieszka; Zochowska, Ewa; Sowińska-Przepiera, Elzbieta; Sagan, Leszek; Kojder, Ireneusz; Syrenicz, Anhelli


    Pituitary gland adenomas producing prolactin are one of the commonest hormonally active tumours. Pharmacological treatment using of dopamine receptors agonists is the therapy of choice in a case of prolactinoma. Bromocriptine, which causes numerous side-effects is the most commonly used drug. Recently, good results of therapy have been achieved with cabergoline - a selective dopamine receptor agonist with prolonged time of action. The aim of the study was to evaluate therapy with cabergoline of men with macroprolactinoma based on clinical, hormonal and radiological examinations. Ten men aged 18-65 (mean 41.9 ?15.01 years) with the presence of a pathological mass in the pituitary gland sized between 16.7 and 40.5 mm (mean 29.8 ± 9.38 mm) and an elevated prolactin (PRL) level of between 37.3 and 4700 ng/mL (mean 1608.2 ±1771.6 ng/mL) were included in the study. The PRL and other trophic hormones levels were evaluated after 1, 3, 6 and 12 months, and tumour size was evaluated by magnetic resonance imaging examination after 12 months of therapy with cabergoline. Results: Therapy with cabergoline led to remission of headaches, visual acuity correction, and a significant improvement in libido and erection in all patients. In 90% of patients, PRL normalisation was achieved, just the initial months of therapy. The mean PRL serum concentrations were before, and after 1, 3, 6 and 12 months of therapy respectively, 1608.2 ± 1771.6 ng/mL and 263.4 ± 223.4, 136.1 ± 244.7,91.31 ± 105.5 and 27.5 ± 57.7 ng/mL. A significant tumour size reduction was observed: from 29.8 ± 9.4 mm to 23.2 ± 9.4 mm, a mean reduction of about 6 mm, or 25.1% (from 4-48.5%). No significant correlation between the mean tumour size and PRL level was observed before or during the treatment. A decreased testosterone level before the therapy was proven, and its gradual increase during the treatment was observed, but after 12 months no normal mean testosterone concentration was achieved. 1. The

  2. Magnetic resonance imaging of pituitary adenoma

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    Handa, Yuji; Hayashi, Minoru; Kubota, Toshihiko; Satoh, Kazufumi; Kobayashi, Hidenori; Kawano, Hirokazu; Kabuto, Masanori; Okumura, Ryousuke


    The magnetic resonance (MR) images of eight patients with pituitary macroadenoma, confirmed by means of CT, were evaluated retrospectively. The examinations were performed with a 0.35 T MR system using short repetition (TR) (T/sub 1/-weighted) and long TR (T/sub 2/-weighted) spin-echo sequences. T/sub 1/-weighted images were obtained on coronal, sagittal, or axial planes with all patients, while T/sub 2/-weighted images were routinely obtained on the axial plane with all patients and on the sagittal or coronal plane in some cases. Detailed information as to the size, configuration, and anatomical relationship, particularly to the optic tract, of the pituitary adenoma were well visualized on sagittal or coronal T/sub 1/-weighted images. The signal intensities from the tumor on T/sub 1/-weighted of T/sub 2/-weighted images were evaluated as iso-, hypo- or hyper-intense with respect to the cortical gray matter. The signal intensities from three non-functioning pituitary adenomas varied from low- to high-intense on the T/sub 1/- or T/sub 2/-weighted images. All the two growth-hormone-producing adenomas showed iso-intense signal intensities on both T/sub 1/- and T/sub 2/-weighted images. One of the two prolactine-producing adenomas were iso-intense on a T/sub 1/-weighted image and low-intense on a T/sub 2/-weighted image, while the other adenoma, when treated with bromocriptine, was iso-intense on both T/sub 1/- and T/sub 2/-weighted images. One adenocorticotropic hormone-producing adenoma was iso-intense on T/sub 1/-weighted and high-intense on T/sub 2/-weighted images. Although the signal intensities on the images, particularly the T/sub 2/-weighted images, were variable, regardless of the type of adenoma, it is presumed that the MR signal arising from a pituitary adenoma affected by the biological or pathological state of the tumor cells.


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    Lucian Hritcu


    role for dopamine in modulating, mainly suppressing immune functions (Qui et al., 1994. Animals treated with bromocriptine, a dopamine agonist, also showed suppression of antibody production to SRBC and LPS (Besedovsky and del Ray, 1996 and suppressed activities of lymphocytes in mixed lymphocyte culture (Hiestand et al., 1986. Moreover, the interest regarding the role of dopamine on immune system becomes more relevant when some of important neurological disease like Parkinson’s disease and schizophrenia with hypo- and hyperactivity (Birtwistle et al., 1988 of central dopamine system are well-correlated with severe abnormalities of immune functions (Muller et al., 1993. Therefore, in the present review, we have evaluated information from our laboratory as well as from others regarding the role of dopamine on immune function in both human and experimental animals in order to understand the current status of dopamine-mediated control of the immunological surveillance system.

  4. Pharmacological treatment for aphasia following stroke. (United States)

    Greener, J; Enderby, P; Whurr, R


    Aphasia describes language impairment associated with a brain lesion. The objective of this review was to assess the effects of drugs on language abilities when given to people with aphasia following stroke. We searched the Cochrane Stroke Group Register (last searched: May 2001), and reference lists of relevant articles to December 1998. We also contacted academic institutions and other researchers to identify further published and unpublished trials. MEDLINE was searched from 1966-1998, and CINAHL from 1982-1998. We searched the International Journal of Disorders of Communication by hand (known by other names in the past), from 1969 to 1998. Randomised controlled trials comparing: ~bullet~Any drug given to improve language, versus no treatment, or versus placebo ~bullet~Any drug given to improve language versus speech and language therapy ~bullet~One drug given to improve language versus another drug given with the same aim The principal reviewer collected the data, and assessed the quality of the trials with independent data checking and methodological advice. If we could not perform a statistical combination of different studies, we sought missing data. Failing that we provided a description. We sought missing data from authors, or where appropriate, a drug company. We considered fifty two studies in detail, from which we identified ten trials suitable for the review. In most cases the methodological quality was unassessable, and only one trial reported sufficient detail for us to complete a description and analysis. This study did lose a large number of patients during its course. Drugs used in the trials identified were piracetam, bifemalane, piribedil, bromocriptine, idebenone, and Dextran 40. We found weak evidence that patients were more likely to have improved on any language measure at the end of the trial if they had received treatment with piracetam (odds ratio 0.46, 95% confidence interval 0.3 to 0.7). The evidence is considered weak because of the