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In the ruminant placenta 15-20% of the trophectodermal epithelium consists of granulated binucleate cells (BNC). In the sheep the granules contain ovine placental lactogen (oPL). These cells migrate from the trophectoderm to form fetomaternal hybrid tissue from implantation to term. The number of BNC, their percentage migration and the potential secretory activity of the syncytium they form were estimated by semiquantitative transmission electron-microscopical techniques after several surgical techniques and hormone or drug infusions. BNC numbers decrease normally just before parturition, and this fall could be eliminated by fetal hypophysectomy or induced early by administration of tetracosactrin to intact or hypophysectomized fetuses. If only one twin was treated with tetracosactrin the placenta of the untreated twin did not show the fall in BNC numbers found in the other unless it died in utero some time before sampling. This indicates fetal control of BNC number and migration. However, fetal catheterization, hypophysectomy, stalk section, adrenalectomy, infusion of mouse epidermal growth factor or bromocriptine had little or no effect on binucleate cell numbers or migration percentages. Maternal carunclectomy, ovariectomy, or epostane or bromocriptine administration also had no consistent significant effect. Previous reports of degeneration of BNC structure plus a decrease in their number (with bromocriptine) or an increase in migration frequency (after adrenalectomy or stalk section) have not been confirmed by this study. The BNC migration delivers the oPL-containing BNC granules close to the maternal circulation but the variation in migration seems only loosely correlated with the reported maternal oPL concentrations. The results indicate that BNC migration is independent of the hormonal milieu, but that BNC production is greatly modified by the hormonal changes just before parturition, with cortisol production by the fetus a possible primary cause.
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We have established that estradiol accelerates apoptosis in the CL during post-partum luteal regression through a mechanism that possibly involves the secretion of pituitary prolactin. We have also shown that the post-partum rat CL express ERalpha and ERbeta mRNAs suggesting that they can be targeted by estrogen.
Dopamine is one of several neurotransmitters that may mediate alcohol intake and dependence. A randomized, double-blind, placebo-controlled international, multicentre study was conducted to assess the effects of a long-acting injectable preparation of bromocriptine, a dopamine agonist, (Parlodel-LAR) in reducing relapse in 366 moderately/severely dependent alcoholics (DSM-III-R), drinking approximately 200 g alcohol (14.5 standard drinks) per day. After detoxification they were randomized to receive six monthly injections of bromocriptine 25 mg (n = 120), bromocriptine 50 mg (n = 124), placebo (n = 122). Brief psychosocial treatment was allowed. At 6 months there were no significant differences between treatment groups in rates of relapse to any drinking or to drinking > or = 5 days per month and > or = 3 drinks per day. Pre-treatment alcohol intake did not determine response. Efficacy ratings by subjects and investigators and adverse events, reported by 51% of subjects, did not differ between treatments. The results of this large study, in which compliance was enhanced by Parlodel-LAR, do not indicate that bromocriptine is efficacious in the maintenance of abstinence or reduced drinking. Possible reasons for the discrepancy between these conclusions and those of some previous clinical trials, in which bromocriptine was reported to reduce symptoms of alcohol withdrawal and dependence, are discussed.
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This article reviews the advances in neurosurgery, neuroradiology, and neuroendocrinology that have altered the management of patients with pituitary adenomas. These benign tumors can produce significant morbidity including loss of vision. Morbidity may be avoided or corrected if available diagnostic and therapeutic options are instituted appropriately.
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Dopamine agonists such as bromocriptine or pergolide are often used in Japan to treat Parkinson's disease. Dopamine agonists are relatively expensive drugs; economic evaluations are required.
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We recorded short latency somatosensory evoked potentials (SEPs) to median nerve stimuli in 40 patients affected by idiopathic Parkinson's disease (PD) classified from I to IV on the Hoehn and Yahr disability scale. SEPs were recorded before and after chronic administration of L-Dopa and bromocriptine, before and after acute administration of L-Dopa. Fourteen patients experiencing wearing off and dystonic-dyskinetic disturbances were recorded during the occurrence of these oscillations of their clinical status. Absent or reduced N30 components were found in 32.5% of patients. SEPs were not modified by acute or chronic administration of L-Dopa or bromocriptine or during off and dystonic or dyskinetic conditions. Multiple correlations of N30 with scores of the Unified Parkinson's Disease Rating Scale showed that N30 abnormality did not classify patients with prominent clinical features, nor did it predict the outcome of treatment.
The striatum is richly innervated by both enkephalinergic and dopaminergic neurons, providing an anatomic framework from which intimate functional interrelationships between these neuronal systems may be postulated. Accordingly, many functional processes within dopamine neurons have been shown to be modulated by opioid peptides. In the present study we confirm predictable reciprocal effects in enkephalin neurons, brought about by modification of dopamine neurotransmission. Dopamine receptor blockade reliably increased striatal Met-enkephalin concentrations by about 50%, whereas chronic treatment with a potent long-acting dopamine receptor agonist was necessary to demonstrate a small 10-20% decrease in Met-enkephalin concentrations. Depletion of presynaptic dopamine also resulted in a marked 50-60% augmentation of Met-enkephalin levels, that could be prevented by concomitant treatment with a dopamine analogue. Increasing dopamine turnover and release by a mu-opioid agonist decreased Met-enkephalin concentrations, as might have been predicted. Thus we have shown a marked dopaminergic influence that maintains striatal Met-enkephalin concentrations by near maximal tonic inhibitory effects.
Seven women with primary amenorrhoea and hyperprolactinaemia were treated with bromocriptine. All the women had started to develop secondary sex characteristics at normal age but pubertal development stopped and menarche did not occur. Radiological signs of a pituitary tumour were found in all the women. Before the pituitary tumour was diagnosed, four women had been given longterm cyclical oestrogen replacement therapy. Three women had received primary tumour therapy with surgery and/or irradiation but had persistent hyperprolactinaemia. The basal luteinizing hormone (LH) levels were low in four of the women while all the women had normal basal levels of follicle-stimulating hormone (FSH) and normal or exaggerated gonadotrophin responses to luteinizing hormone-releasing hormone (LHRH). None of the women had evidence of endogenous oestrogen production before treatment. Bromocriptine treatment normalized the raised serum prolactin levels (46-2900 microgram/l) in all but one woman, in whom the prolactin level decreased from 160 to 38 microgram/l. Regular ovulatory menstrual cycles appeared in four women, one of whom had previously been treated by transsphenoidal adenomectomy followed by external irradiation. Two other women with persistent hyperprolactinaemia after previous surgical and/or irradiation treatment of large pituitary tumours did not menstruate after more than one year of treatment with bromocriptine. One infertile patient with a microadenoma conceived at the first ovulation on therapy and developed symptoms and signs of tumour growth during pregnancy.
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A 24-year-old African American woman hospitalized for psychosis was unresponsive to risperidone. Because of obsessive symptoms, low doses of fluvoxamine were added to her treatment regimen. Within 2 days, she developed confusion, diaphoresis, diarrhea, hyperreflexia, and myoclonus, which then progressed to rigidity, fever, and unresponsiveness, requiring endotracheal intubation. Symptoms resolved over 10 days with discontinuation of medication, hydration, and bromocriptine 5 mg 3 times daily. Ultimately, she was treated with olanzapine and fluvoxamine without adverse effects.
The aim of this revision is to explore the possible role of the prolactin in the immune response. The prolactin is a hormone secreted by the pituitary. However, it has a trophic function in the proliferation of the lymphocytes. The cell of the immune system show outer membrane receptor for the prolactin. Moreover, the lymphocytes are capable to produce and secret prolactin. In cell culture, different levels of prolactin show different immune responses- low levels of prolactin awake a weak immune response. In contrast, high levels of prolactin show a strong immune response. Alteration in the sera levels of prolactin has been describes in severe autoimmune disease like systemic lupus erythematosus. Reiter syndrome, adjuvant arthritis, uveitis etc. Until now many evidences has been reported about the roles of the prolactin in the immune response acting like an immunomodulator, but the relevance of this phenomena in the clinical practice is still unclear.
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Prolactin-secreting pituitary adenomas were studied to clarify the mechanism by which bromocriptine reduces tumor size. Patients examined consisted of three groups: Group I (four cases) received no medication, Group II (six cases) continued bromocriptine treatment (10 mg/day for 2 weeks) until the operation, and Group III (five cases) discontinued the treatment 1 week before the operation. Adenomas in Group II showed a variety of degenerative and necrotic changes of tumor cells in addition to marked decrease in volume of individual cell. Adenomas in Group III showed divergent structural changes. Irreversible changes seen in Group II became more pronounced with a marked increase in stromal tissue. Proliferative areas consisting of intermediate-sized cells were found in the scarce stromal tissue. The findings seem to indicate that the reduction in size of prolactinomas by bromocriptine treatment results from the reduction in size of individual tumor cell as well as from cell loss secondary to necrosis.
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Adjuvant arthritis was induced in female Fisher rats by injecting their right hind paw with 0.1 ml Freund's complete adjuvant. The development of adjuvant arthritis was inhibited by hypophysectomy and by daily treatment of intact animals with the dopaminergic agent bromocriptine. Adjuvant arthritis developed normally if hypophysectomized or bromocriptine-suppressed animals were treated with either prolactin or growth hormone. Additional treatment with adrenocorticotropic hormone inhibited this restoration. Treatment of hypophysectomized rats with follicle-stimulating hormone, luteinizing hormone, and thyroid-stimulating hormone had no effect. These results indicate that prolactin and/or growth hormone are necessary for the development of adjuvant arthritis, whereas adrenocorticotropic hormone has an inhibitory effect.
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Results of autonomic testing were compared with those of a group of age-matched healthy subjects. A value of AS>2 was considered as indicative of autonomic failure. Eighteen patients with PD (35%) showed AS>2 (autonomically impaired group=AI), the remaining 33 (65%) had AS<2 (nonautonomically impaired group=non-AI). During the follow-up levodopa was added to the treatment regimen of 10/18 (55%) patients in AI group, and 6/33 (18%) patients in non-AI group (p<.01).
We have investigated the DA, serotonergic (5-HT), and noradrenergic (NE) functions in 22 abstinent heroin addicts and 22 healthy controls by challenging the monoamine systems with the DA agonist bromocriptine (brom), the 5-HT agonist D-fenfluramine (D-fen), and the NE agonist clonidine (clon), respectively. We examined the temperament traits by measuring NS, harm avoidance (HA), and reward dependence (RD) using the "Three-Dimensional Personality Questionnaire" (TPQ).
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We report five cases of TSH-oma diagnosed between 1997 and 2006 and review the literature. All the patients are females with an age range from 54 to 65 years at diagnosis. Four of the five patients had at least one event of thyroid surgery due to goiter or nodule of unknown dignity. Three of the five patients had a stroke before the diagnosis of TSH-oma, probably due to hypertension, or smoking and contraceptive treatment. One patient with invasive tumor growth received stereotactic radiotherapy (and developed panhypopituitarism after operation), another patient received somatostatin analogs preoperatively and successfully underwent transsphenoidal operation. Three of the five patients received dopaminergic agonists (bromocriptine 5 mg daily or cabergoline 0.5-0.75 mg per week), because they refused surgical therapy or the tumor was stable under dopaminergic therapy. All patients have been followed-up for 2.5-8 years. A normalization of circulating thyroid hormone levels was achieved in all patients. The patient who underwent operation shows no recurrence of the disease. The other patients have a stable pituitary mass without signs of growth.
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The use of CsA has evolved considerably in concept and practice since the First International Congress on this drug in 1983. CsA is now increasingly used as a component of a multiagent protocol, rather than as a single, potent agent, with adjunctive therapy selected to optimize induction or maintenance immunosuppression. Novel clinical developments include the prophylactic use of the MoAb OKT3 as an alternative to polyclonal ALG, and the coadministration of bromocriptine to inhibit prolactin-dependent immune augmentation. Other combinations with site-selective pharmacologic agents are now under investigation in vitro or in vivo to improve both the selectivity and potency of immunosuppression while reducing further the toxicity and cost of CsA. With the introduction of MoAb to CsA, rapid and specific measurement of the parent molecule will now become widely possible. Because of its simplicity and rapidity, this technique may well replace HPLC for routine monitoring, although the latter will remain indispensable in a research setting for measurement of individual metabolites. Specific measurement of the parent molecule is clearly important in heart or liver transplantation when hepatic metabolism is frequently grossly disturbed. There is less evidence that this will prove of value in renal transplantation, however, and it remains possible that by virtue of the biologic effect of certain metabolites, a more broadly crossreactive polyclonal assay is equal or superior in this setting. In this regard, the fluorescence polarization immunoassay is particularly attractive as a clinical monitoring system. It is simple, accurate, and cost-effective, and by virtue of its automation and speed, particularly adapted to outpatient monitoring. The planned introduction of new kits allowing measurement by monoclonal or polyclonal antibody in either serum or whole blood will make this a versatile system for the measurement of CsA.
Conventional radiotherapy is not as effective as expected, considering its adverse effects. The increased side effects of radiotherapy in cases with supra-parasellar extension, especially to the optic pathway and hypothalamus, limit its benefits, which could be demonstrated only in invasive somatotropinomas and null cell adenomas. In contrast with our current beliefs, tumoral infiltration of the sellar dura mater is not a prognostic factor for recurrence and therefore should not be a criterion for radiotherapy after surgery. Topical application of bromocriptine into the sellar cavity after tumor removal seems to provide superior results compared with the conventional treatment modalities.
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The neutrotransmitter dopamine mediates its central nervous system actions via 2 types of receptors: D1 and D2, each of which exist in a low or a high affinity state. In schizophrenic patients, it appears that part of the symptomatology may be secondary to dopaminergic hyperactivity (the so called positive symptoms), whereas negative symptoms would be secondary to structural damage. Antipsychotic drugs that are used in clinics are antidopaminergic. It is interesting to note that those drugs are ineffective in part of the schizophrenic population, the chronic one. This inefficiency might be due to primary resistance or to adaptation of the central nervous system to the drugs. Some authors tried dopamine agonists to treat schizophrenic patients. Apomorphine, N-n-propylnorapomorphine, l-DOPA and bromocriptine were tried. The purpose of these substances was to desensitize dopaminergic system, or to inhibit it via presynaptic autoreceptor stimulation, depending of the study. Some authors hypothesized a drop in frontal cortical dopaminergic system to explain part of the schizophrenic symptomatology. Dopamine agonists might act at this level to enhance frontal dopaminergic activity. After those experimentations with dopamine agonist drugs, it appears that 2 of them might have efficiency and clinical use: l-DOPA and bromocriptine.
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Biologically inactive thyroid stimulating hormone (TSH) has been reported in hypothyroid patients. We report the first case of immunoreactive, but abnormal TSH in a euthyroid patient following hypophysectomy for a prolactin secreting pituitary adenoma. Indirect evidence indicates that this abnormal TSH was biologically inactive. The TSH was characterized by gel chromatography and has a molecular weight of approximately 23,000 daltons.
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Anomia is a commonly found in aphasia and has been attributed to a loss of representations (storage deficit) or to a loss of access to these representations (retrieval deficit). Bromocriptine, a dopamine agonist, was tested on four patients, two men and two women, with nonfluent aphasia. The patients were tested in an open-label ABBA design using a stochastic model that measured the degree of storage and retrieval deficits. All patients showed significant improvements in word retrieval. Bromocriptine may be a useful adjunct in the treatment of selected patients with a nonfluent aphasia in which retrieval deficits play a major role.