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Journal of Neurological Surgery Reports Apr 2024Prolactinomas are a common intracranial neoplasm and constitute most pituitary tumors. Although patients can present with variable hormone dysregulation and symptom...
Prolactinomas are a common intracranial neoplasm and constitute most pituitary tumors. Although patients can present with variable hormone dysregulation and symptom severity, the use of dopamine agonists remains a first-line treatment. While bromocriptine has been found to increase tumor fibrosis, the effect of cabergoline on collagen deposition has been disputed. The aim of this article is to understand the influence of cabergoline on tumor fibrosis prior to resection. Four male patients who underwent prolactinoma resection were included in this report. The average age was 39.8 years (range: 26-52 years). Pre-treatment prolactin levels ranged from 957.8 to 16,487.4 ng/mL. Three patients received cabergoline for at least 1 month prior to surgery (treatment range: 1-6 months). One patient had surgery without prior cabergoline use. Pathology reports confirmed each tumor to be of lactotroph origin. For each sample, Masson's trichrome staining was performed and the percentage of sample fibrosis was quantified using an artificial intelligence imaging software. Among those who received preoperative cabergoline, the extent of tumor fibrosis was in the range of 50 to 70%. In contrast, specimen fibrosis was approximately 15% without cabergoline use. This report demonstrates that a short duration of preoperative cabergoline can cause significant prolactinoma fibrosis. Understanding the effect of cabergoline on tumor consistency prior to surgery is essential as increased fibrosis can lead to more difficult tumor removal, reduce the extent of resection, and increase surgical complications. Considering these effects, further studies regarding the use of surgery prior to cabergoline for prolactinoma management are warranted.
PubMed: 38751869
DOI: 10.1055/s-0044-1786740 -
Science Bulletin Apr 2024Molecular glues are typically small chemical molecules that act at the interface between a target protein and degradation machinery to trigger ternary complex formation....
Molecular glues are typically small chemical molecules that act at the interface between a target protein and degradation machinery to trigger ternary complex formation. Identifying molecular glues is challenging. There is a scarcity of target-specific upregulating molecular glues, which are highly anticipated for numerous targets, including P53. P53 is degraded in proteasomes through polyubiquitination by specific E3 ligases, whereas deubiquitinases (DUBs) remove polyubiquitination conjugates to counteract these E3 ligases. Thus, small-molecular glues that enhance P53 anchoring to DUBs may stabilize P53 through deubiquitination. Here, using small-molecule microarray-based technology and unbiased screening, we identified three potential molecular glues that may tether P53 to the DUB, USP7, and elevate the P53 level. Among the molecular glues, bromocriptine (BC) is an FDA-approved drug with the most robust effects. BC was further verified to increase P53 stability via the predicted molecular glue mechanism engaging USP7. Consistent with P53 upregulation in cancer cells, BC was shown to inhibit the proliferation of cancer cells in vitro and suppress tumor growth in a xenograft model. In summary, we established a potential screening platform and identified potential molecular glues upregulating P53. Similar strategies could be applied to the identification of other types of molecular glues that may benefit drug discovery and chemical biology studies.
PubMed: 38734583
DOI: 10.1016/j.scib.2024.04.017 -
Journal of Gynecology Obstetrics and... Jun 2024This systematic review aims to evaluate the efficacy and safety of Pyridoxine compared to Dopaminergic agonists (cabergoline and bromocriptine) in post-partum lactation... (Comparative Study)
Comparative Study Review
This systematic review aims to evaluate the efficacy and safety of Pyridoxine compared to Dopaminergic agonists (cabergoline and bromocriptine) in post-partum lactation inhibition. Cochrane Central, PubMed/MEDLINE, Cochrane Central, ScienceDirect, ClinicalTrials.gov, Web of Science, CINAHL and Google Scholar, covering the period from inception to November 2023. Additionally, the bibliographies of included articles and previous meta-analyses were screened for any relevant articles. The systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The outcomes of interest encompassed inhibition of lactation, breast pain/tenderness, breast engorgement, milk secretion, fever, mastitis, prolactin level and adverse events related to pyridoxine, cabergoline and bromocriptine. Methodological quality assessment was conducted using the Cochrane risk of bias assessment tool for rigorous evaluation. Three clinical trials assessed the effectiveness of pyridoxine and dopaminergic agents (cabergoline and bromocriptine) for lactation inhibition. It was assessed by using different assessment methods such as a scale for milk secretion, serum prolactin levels, and questionnaires for assessing breast engorgement, breast pain, and milk leakage. On the global assessment of the therapeutic efficacy of dopaminergic agents, it was found that there was significant inhibition of lactation as compared to pyridoxine (p < 0.001). In conclusion, this systematic review contributes significant insights into lactation inhibition interventions. Dopaminergic agonists, specifically cabergoline and bromocriptine, stand out as more effective and tolerable choices compared to Pyridoxine. These findings provide a foundation for informed clinical decisions and underscore the need for careful consideration of lactation inhibition strategies in diverse clinical contexts.
Topics: Humans; Bromocriptine; Female; Pyridoxine; Cabergoline; Dopamine Agonists; Lactation; Lactation Disorders; Clinical Trials as Topic
PubMed: 38554942
DOI: 10.1016/j.jogoh.2024.102783 -
Pharmacology, Biochemistry, and Behavior Jun 2024Pituitary lactotrophs are under tonic dopaminergic inhibitory control and bromocriptine treatment blocks prolactin secretion.
BACKGROUND
Pituitary lactotrophs are under tonic dopaminergic inhibitory control and bromocriptine treatment blocks prolactin secretion.
METHODS
Sleep and local field potential were addressed for 72 h after bromocriptine treatments applied during the different stages of the estrus cycle and for 24 h in the early- and middle postpartum period characterized by spontaneously different dynamics of prolactin release in female rats.
RESULTS
Sleep changes showed strong dependency on the estrus cycle phase of the drug application. Strongest increase of wakefulness and reduction of slow wave sleep- and rapid eye movements sleep appeared during diestrus-proestrus and middle postpartum treatments. Stronger sleep-wake effects appeared in the dark phase in case of the estrus cycle treatments, but in the light phase in postpartum treatments. Slow wave sleep and REM sleep loss in case of estrus cycle treatments was not compensated at all and sleep loss seen in the first day post-injection was gained further later. In opposition, slow wave sleep loss in the light phase after bromocriptine injections showed compensation in the postpartum period treatments. Bromocriptine treatments resulted in a depression of local field potential delta power during slow wave sleep while an enhancement in beta and gamma power during wakefulness regardless of the treatment timing.
CONCLUSIONS
These results can be explained by the interplay of dopamine D2 receptor agonism, lack of prolactin release and the spontaneous homeostatic sleep drive being altered in the different stages of the estrus cycle and the postpartum period.
Topics: Animals; Bromocriptine; Female; Postpartum Period; Rats; Receptors, Dopamine D2; Dopamine Agonists; Estrous Cycle; Rats, Wistar; Sleep; Wakefulness; Prolactin
PubMed: 38537873
DOI: 10.1016/j.pbb.2024.173754 -
BioRxiv : the Preprint Server For... Feb 2024Dopamine (DA) D-like receptors in both the central nervous system (CNS) and the periphery are key modulators of metabolism. Moreover, disruption of D-like receptor...
Dopamine (DA) D-like receptors in both the central nervous system (CNS) and the periphery are key modulators of metabolism. Moreover, disruption of D-like receptor signaling is implicated in dysglycemia. Yet, the respective metabolic contributions of CNS versus peripheral D-like receptors including D (D2R) and D (D3R) receptors remain poorly understood. To address this, we developed new pharmacological tools, D-like receptor agonists with diminished and delayed blood-brain barrier capability, to selectively manipulate D2R/D3R signaling in the periphery. We designated bromocriptine methiodide (BrMeI), a quaternary methiodide analogue of D2/3R agonist and diabetes drug bromocriptine, as our lead compound based on preservation of D2R/D3R binding and functional efficacy. We then used BrMeI and unmodified bromocriptine to dissect relative contributions of CNS versus peripheral D2R/D3R signaling in treating dysglycemia. Systemic administration of bromocriptine, with unrestricted access to CNS and peripheral targets, significantly improved both insulin sensitivity and glucose tolerance in obese, dysglycemic mice . In contrast, metabolic improvements were attenuated when access to bromocriptine was restricted either to the CNS through intracerebroventricular administration or delayed access to the CNS via BrMeI. Our findings demonstrate that the coordinated actions of both CNS and peripheral D-like receptors are required for correcting dysglycemia. Ultimately, the development of a first-generation of drugs designed to selectively target the periphery provides a blueprint for dissecting mechanisms of central versus peripheral DA signaling and paves the way for novel strategies to treat dysglycemia.
PubMed: 38529497
DOI: 10.1101/2024.02.21.581451 -
International Journal of General... 2024Due to the rarity of peripartum cardiomyopathy (PPCM) globally, baseline characteristic data for PPCM patients are still scarce. Therefore, this study aims to determine...
BACKGROUND
Due to the rarity of peripartum cardiomyopathy (PPCM) globally, baseline characteristic data for PPCM patients are still scarce. Therefore, this study aims to determine the baseline characteristics and 6-month outcomes of PPCM patients in Indonesia.
METHODS
From January 2014 to December 2021, all PPCM patients aged ≥18 years who were admitted to Dr. Hasan Sadikin General Hospital in Bandung, Indonesia, participated in this single-center, prospective cohort study. All patients were re-evaluated within 6 months of PPCM diagnosis.
RESULTS
A total of 138 patients with PPCM were admitted to Dr. Hasan Sadikin General Hospital in Bandung. The mean age of all patients was 30.4 ± 6.4 years old. Approximately 60% patients were multipara and had preeclampsia. All guideline-directed medical therapy for heart failure was received by most patients, excluding mineralocorticoid receptor antagonists (25.2%) and bromocriptine (14.1%). The neonatal mortality rate was 5.1%. Among those who survived, 61.2% had normal weight, 31.8% had low birth weight, and 7% had very low birth weight. At the 6-month follow-up, 6.7% of the patients died, 63.3% recovered, and 1.9% were rehospitalized.
CONCLUSION
The present study found a high incidence of PPCM in Indonesia. Our patients frequently had preeclampsia, which contributed to the higher rate of miscarriage and low birth weight. Our liberal use of beta-blockers and ACEi/ARB may have contributed to the higher 6-month recovery rate than that in other countries.
PubMed: 38529099
DOI: 10.2147/IJGM.S447214 -
Journal of Cardiology Cases Mar 2024Peripartum cardiomyopathy (PPCM) is a rare disorder in which left ventricular systolic dysfunction and heart failure symptoms occur during the peripartum period....
UNLABELLED
Peripartum cardiomyopathy (PPCM) is a rare disorder in which left ventricular systolic dysfunction and heart failure symptoms occur during the peripartum period. Inhibition of prolactin secretion by bromocriptine mediates beneficial effects on cardiac function in PPCM. Mental disorders are also associated with the onset of PPCM. Psychiatric medications for mental disorders would affect serotonin production and tryptophan and dopamine metabolism, and they are associated with PPCM. Conversely, bromocriptine affects psychiatric symptoms; therefore, the treatment of PPCM complicated by mental disorders using bromocriptine may be difficult. Herein, we report cases of two patients with PPCM and mental disorders successfully treated with bromocriptine therapy. The first case involved a 33-year-old woman with a history of atypical depression and anxiety disorder, who developed PPCM with a left ventricular ejection fraction (LVEF) of 19 %. The second case was that of a 42-year-old woman with a history of bipolar and panic disorders who developed PPCM with an LVEF of 18 %. Both patients were administered bromocriptine; however, psychiatric symptoms did not worsen and cardiac function improved. We also review the literature on the relationship between PPCM and mental disorders.
LEARNING OBJECTIVE
Mental disorders and psychiatric medications may be associated with the onset of peripartum cardiomyopathy (PPCM). Although bromocriptine has beneficial effects on PPCM, it has also been reported to increase the risk of worsening psychiatric symptoms; therefore, the efficacy and safety of bromocriptine in PPCM patients with mental disorders is controversial. Our cases showed that bromocriptine can be used safely without worsening psychiatric symptoms in PPCM with mental disorders.
PubMed: 38481642
DOI: 10.1016/j.jccase.2023.11.014 -
Clinical Case Reports Mar 2024Sexual dysfunction induced by hyperprolactinemia accompanied by reduced luteinizing hormone (LH) is common in anrology clinics. A low dose of bromocriptine is helpful...
KEY CLINICAL MESSAGE
Sexual dysfunction induced by hyperprolactinemia accompanied by reduced luteinizing hormone (LH) is common in anrology clinics. A low dose of bromocriptine is helpful for restoring penile erectile function and libido in patients.
ABSTRACT
Sexual dysfunction is closely related to hormonal disorders, of which prolactin (PRL) and luteinizing hormone (LH) disorders are common. How to treat sexual dysfunction induced by hyperprolactinemia accompanied by reduced LH levels is worth discussing. In this study, we aimed to present the case of a 35-year-old male patient with sexual dysfunction. The treatment process and physical and laboratory examination results were recorded. Before treatment, the PRL and LH levels in this patient were 31.27 ng/mL and 1.62 mIU/mL, respectively. The International Index of Erectile Function-5 (IIEF-5) score was initially 14 points. After regular treatment with low doses of bromocriptine and tadalafil, the hormonal disorder was corrected (PRL: 11.16 ng/mL and LH: 2.28 mIU/mL) and sexual function was recovered (IIEF-5: 23 points). This case report suggested a sufficient exposure to low-dose bromocriptine for such patients. Conversely, the exogenous supplementation of human chorionic gonadotropin may not be appropriate.
PubMed: 38435507
DOI: 10.1002/ccr3.8432 -
BMC Ophthalmology Mar 2024Acute retinal pigment epitheliitis (ARPE) is a rare, idiopathic and self-limiting disease. The article aims to present ARPE in a patient using D2 dopamine receptor...
BACKGROUND
Acute retinal pigment epitheliitis (ARPE) is a rare, idiopathic and self-limiting disease. The article aims to present ARPE in a patient using D2 dopamine receptor agonists for the treatment of hyperprolactinemia.
CASE PRESENTATION
A 28-year-old female during hyperprolactinaemia treatment suffered from a dyschromatopsia and a central visual field defect in the left eye. She noticed a deterioration of vision and discontinued the cabergoline administration. The woman had not been diagnosed with other chronic conditions and exhibited no symptoms of infection. Upon admission, the patient was subjected to a test for COVID-19, which was negative. The ophthalmological examination revealed a decrease in visual acuity to distance in the left eye, which amounted to 18/20 on the Snellen chart. A central scotoma was noted on the Amsler chart and a loss of pigment epithelium was visible on the fundus of the left eye. Fluorescein angiography showed a discrete window defect in the left one, with no signs of leakage. Optical coherence tomography (OCT) scans of the maculae revealed a characteristic change in the photoreceptor layer and retinal pigment epithelium (RPE) in the fovea in the left eye. The electrophysiological tests revealed decreased function of cells in macular region. A magnetic resonance imaging (MRI) of the head and orbits demonstrated an asymmetric pituitary gland without chiasm compression and discrete signal enhancement from the left optic nerve. The patient underwent observation during hospitalisation. She reported improved colour vision and a decreased scotoma in the centre of her visual field. In regular outpatient follow-ups, successive improvements in visual acuity, as well as a decreased RPE damage and outer photoreceptor layer loss during an OCT test were observed.
CONCLUSIONS
A case of ARPE is reported in a patient taking medications for hyperprolactinemia. The role of dopamine receptor antagonists in the photoreceptor function and causation of ARPE needs further evaluation.
Topics: Humans; Female; Adult; Hyperprolactinemia; Retinitis; Visual Fields; Scotoma; Retinal Pigments
PubMed: 38429692
DOI: 10.1186/s12886-024-03366-0