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Inherited retinopathies are devastating diseases that in most cases lack treatment options. Disease-modifying therapies that mitigate pathophysiology regardless of the underlying genetic lesion are desirable due to the diversity of mutations found in such diseases. We tested a systems pharmacology-based strategy that suppresses intracellular cAMP and Ca2+ activity via G protein-coupled receptor (GPCR) modulation using tamsulosin, metoprolol, and bromocriptine coadministration. The treatment improves cone photoreceptor function and slows degeneration in Pde6βrd10 and RhoP23H/WT retinitis pigmentosa mice. Cone degeneration is modestly mitigated after a 7-month-long drug infusion in PDE6A-/- dogs. The treatment also improves rod pathway function in an Rpe65-/- mouse model of Leber congenital amaurosis but does not protect from cone degeneration. RNA-sequencing analyses indicate improved metabolic function in drug-treated Rpe65-/- and rd10 mice. Our data show that catecholaminergic GPCR drug combinations that modify second messenger levels via multiple receptor actions provide a potential disease-modifying therapy against retinal degeneration.

Recent studies have highlighted leptin, a key hormone that regulates energy intake and induces satiety, due to the worldwide prevalence of obesity. In this study, we analyzed plasma leptin measurements from 18 women with premenopausal obesity before and after bromocriptine treatment. By using underlying pulses recovered through deconvolution, we modeled the leptin secretory pulses as marked point processes and applied statistical distributions to evaluate the dynamics of leptin, including the interpulse intervals and amplitudes of the secretion. We fit the generalized inverse Gaussian and lognormal distributions to the intervals and the Gaussian, lognormal, and gamma distributions to the amplitudes of pulses. We evaluated the models' goodness of fit using statistical metrics including Akaike's information criterion, Kolmogorov-Smirnov plots, and quantile-quantile plots. Our evaluation results revealed the effectiveness of these statistical distributions in modeling leptin secretion. Although the lognormal and gamma distributions performed the best based on the metrics, we found all distributions capable of accurately modeling the timing of secretory events, leading us to a better understanding of the physiology of leptin secretion and providing a basis for leptin monitoring. In terms of pulse amplitude, the evaluation metrics indicated the gamma distribution as the most accurate statistical representation. We found no statistically significant effect of bromocriptine intake on the model parameters except for one distribution model. [ABSTRACT FROM AUTHOR]

Dopamine (DA) D2-like receptors in both the central nervous system (CNS) and the periphery are key modulators of metabolism. Moreover, disruption of D2-like receptor signaling is implicated in dysglycemia. Yet, the respective metabolic contributions of CNS versus peripheral D2-like receptors, including D2 (D2R) and D3 (D3R) receptors, remain poorly understood. To address this, we developed new pharmacological tools, D2-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 analog of D2R/D3R 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 vivo. 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 D2-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. Article Highlights: We developed new pharmacological tools with diminished blood-brain barrier capability to selectively manipulate peripheral dopamine D2-like receptor signaling. Our lead compound, bromocriptine methiodide (BrMeI), shows preserved dopamine D2-like receptor binding and functional efficacy. We used BrMeI and unmodified bromocriptine to dissect relative contributions of central nervous system versus peripheral dopamine signaling in treating dysglycemia. Systemic administration of the dopaminergic agonist bromocriptine significantly improves dysglycemia, while metabolic improvements are attenuated after restricting access to the brain or periphery via BrMeI. Tandem, coordinated actions of both brain and peripheral dopamine D2-like receptors are required for correcting dysglycemia. [ABSTRACT FROM AUTHOR]

Background: Peripartum cardiomyopathy (PPCM) presents a significant global health challenge, contributing substantially to maternal morbidity and mortality worldwide. Despite ongoing research efforts, the multifaceted nature of PPCM, encompassing genetic, environmental, and clinical factors, necessitates a comprehensive understanding to improve patient outcomes effectively. Aims: This systematic review aims to synthesise current knowledge on PPCM aetiology, risk factors, diagnosis, therapeutic interventions, and prognostic indicators, highlighting recent advancements and potential avenues for future research and clinical management. By addressing key aspects such as genetic predispositions, environmental influences, diagnostic strategies, therapeutic modalities, and global disparities, this review seeks to provide insights that can inform interdisciplinary approaches and ultimately enhance the care and outcomes of affected patients on a global scale. Methodology: Narrative, qualitative systematic review of current literature Results: This systematic review delved into the multifaceted landscape of PPCM, revealing genetic, environmental, and clinical intricacies. Key findings included the identification of TTN truncating mutations as a significant genetic predisposition, prompting personalised medical interventions. Environmental factors, such as PM2.5 exposure, intersected with clinical dynamics, highlighting the need for interdisciplinary cooperation in healthcare and environmental policy. Additionally, studies emphasised the importance of timely diagnosis, global disparities in PPCM incidence, and the potential for personalised treatments like bromocriptine and targeted genetic therapies. Conclusion: This review illuminated the complexity of peripartum cardiomyopathy and provides a roadmap for future research and clinical management, advocating for holistic approaches to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Maternal Parathyroid Hormone-related Protein (PTHrP) is involved in the placental transport of calcium. Autonomous overproduction of PTHrP is a rare cause of hypercalcemia in pregnancy. Prior cases of PTHrP-induced hypercalcemia in pregnancy have been managed with either dopamine agonists, fetal delivery, termination of pregnancy, or mastectomy. However, PTHrP level normalization following mastectomy has not previously been documented. Herein, we present a 39-year-old female hospitalized at 19 weeks of gestation for acute encephalopathy due to PTHrP induced hypercalcemic crisis (calcium 15.8 mg/dL, PTHrp 46.5 pmol/L [normal 0-3.4]). Mammary hyperplasia resulting in gigantomastia significantly impaired her ability to ambulate and perform activities of daily living. She remained hypercalcemic during hospitalization despite aggressive hydration, calcitonin, and 2 weeks of dopamine agonist treatment. Bisphosphonate therapy was not administered due to pregnancy and potential effects on the fetus. Our patient underwent bilateral mastectomy along with excision of a large axillary mass. The pathology of all three specimens revealed mammary stromal hyperplasia. PTHrP was undetectable on post-op day 2 and calcium normalized by post-op day 3. At discharge, she was able to ambulate independently. To our knowledge, this is the first reported case of PTHrP induced hypercalcemia related to gigantomastia, documenting resolution of hypercalcemia, and PTHrP levels following mastectomy. Mastectomy is a potential option in the second trimester for pregnant patients with PTHrP induced severe hypercalcemia due to gigantomastia, refractory to treatment with dopamine agonist therapy. Lay Summary: Parathyroid Hormone-related Protein (PTHrP) is important for transportation of calcium during pregnancy, facilitating fetal skeleton formation. Rarely, excess production of PTHrP can cause critically elevated calcium levels in pregnancy. We present a 39-yr-old female hospitalized at 19 wk of gestation for altered mental status, due to PTHrP-induced hypercalcemic crisis. She demonstrated profound breast enlargement and a left axillary mass, impairing her ability to walk and work. Despite aggressive hydration, and medical treatment targeted to lower calcium, her calcium remained significantly elevated. She underwent surgical removal of both breasts and excision of the axillary mass which each demonstrated mammary stromal hyperplasia. PTHrP levels became undetectable, and calcium quickly normalized. To our knowledge, this is the first reported documentation of resolution of hypercalcemia and PTHrP levels following surgical resection of the excess breast enlargement during pregnancy. Graphical Abstract [ABSTRACT FROM AUTHOR]

Bromocriptine is a dopamine receptor agonist used for central hyperthermia with limited data. We describe our single-center experience utilizing bromocriptine for central hyperthermia, including the population treated, most common dosing regimens, adverse events, and discontinuation reasons. A retrospective study was conducted screening patients who were admitted to intensive care units for acute neurological insults and administered bromocriptine for central hyperthermia between April 2016 and September 2022. Baseline characteristics, disease severity markers, and bromocriptine doses were collected. Body temperatures prior to the first dose of bromocriptine, at the time of dose, and after each dose were recorded. Co-administration of additional hyperthermia management therapies was noted. Thirty patients were included. The most common diagnosis was traumatic brain injury (TBI) (N = 14). The most common reason for discontinuation was resolution of indication (N = 14). Discontinuation due to mild adverse effects occurred in four patients; hepatotoxicity was the most common. There was a paired mean difference of −0.37°C (p = 0.005) between temperatures before and after bromocriptine initiation. Bromocriptine is a potential therapy for the management of central hyperthermia in patients with severe acute neurologic insults who have failed other therapies. Bromocriptine was well tolerated and associated with a low incidence of adverse events. [ABSTRACT FROM AUTHOR]

[Display omitted] 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. [ABSTRACT FROM AUTHOR]

The survival and proliferation of proliferating cancer cells is largely dependent on glutamine. Glutamine serves as a nitrogen source for the synthesis of amino acids and nucleotides, and as a carbon source for the synthesis of lipids. Virtual screening of FDA‐approved drugs is a promising approach to identify new glutaminase inhibitors. In this study, molecular docking were used to screen a library of FDA‐approved drugs against glutaminase. Their potential as inhibitors for the treatment of breast cancer was evaluated. Molecular dynamics simulations were performed on promising candidates. An in vitro study using two breast cancer cell lines, MDA‐MB‐231 and MCF‐7, was performed to evaluate the effect of the selected drugs on cell viability and expression of apoptosis‐related genes. Our results identified several FDA‐approved drugs with potential inhibitory activity against glutaminase, including bromocriptine, doxycycline, dutasteride, ezetimibe, fexofenadine, montelukast, pimozide, and tetracycline. In vitro assays revealed a dose‐dependent inhibitory effect of rifampin and bromocriptine, two drugs with the highest binding affinity to glutaminase, on cell viability and apoptosis‐related genes in breast cancer cell lines. Targeting glutaminase with FDA‐approved drugs may be a promising strategy for the development of new cancer therapies, especially for breast cancer. [ABSTRACT FROM AUTHOR]

Bromocriptine (BCR) presents poor bioavailability when administered orally because of its low solubility and prolonged first-pass metabolism. This poses a significant challenge in its utilization as an effective treatment for managing Parkinson's disease (PD). The utilization of lipid nanoparticles can be a promising approach to overcome the limitations of BCR bioavailability. The aim of the research work was to develop and evaluate bromocriptine-loaded solid lipid nanoparticles (BCR-SLN) and bromocriptine-loaded nanostructured lipid carriers (BCR-NLC) employing the Box-Behnken design (BBD). BCR-SLNs and BCR-NLCs were developed using the high-pressure homogenization method. The prepared nanoparticles were characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE). In vitro drug release, cytotoxicity studies, in vivo plasma pharmacokinetic, and brain distribution studies evaluated the optimized lipid nanoparticles. The optimized BCR-SLN had a PS of 219.21 ± 1.3 nm, PDI of 0.22 ± 0.02, and EE of 72.2 ± 0.5. The PS, PDI, and EE of optimized BCR-NLC formulation were found to be 182.87 ± 2.2, 0.16 ± 0.004, and 83.57 ± 1.8, respectively. The in vitro release profile of BCR-SLN and BCR-NLC showed a biphasic pattern, immediate release, and then trailed due to the sustained release. Furthermore, a pharmacokinetic study indicated that both the optimized BCR-SLN and BCR-NLC formulations improve the plasma and brain bioavailability of the drug compared to the BCR solution. Based on the research findings, it can be concluded that the BCR-loaded lipid nanoparticles could be a promising carrier by enhancing the BBB penetration of the drug and helping in the improvement of the bioavailability and therapeutic efficacy of BCR in the management of PD. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure associated with pregnancy without any other known cause. With a prognosis that can vary from the complete recovery of left ventricular function to maternal mortality as well as recurrence with subsequent pregnancies, early diagnosis and treatment of PPCM is important in management. Bromocriptine treatment is beneficial effects on LVEF and mortality in women with severe acute PPCM in addition to standard heart failure therapy. However, further study is required to establish its effect in PPCM. Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure associated with pregnancy without any other known cause. Most of the clinical presentation is similar to symptoms of advanced pregnancy making the diagnosis difficult. Reported are three patients who developed dyspnea, orthopnea, and dry cough during the first week of puerperium. On examination, bilateral lower limb edema and bilateral basal lung crepitation were present in all patients. Chest radiograph showed pulmonary edema in cases two and three, and pleural effusion in case one. All patients had reduced left ventricular ejection fraction and raised N‐terminal pro‐b‐type natriuretic peptide (NT‐proBNP) levels. Case two developed PPCM in the background of left pyelonephritis. Case three was complicated by acute kidney injury. All patients were managed with bromocriptine, diuretics, beta‐blockers, ACE inhibitors, and fluid restriction. Hence, PPCM though rare should be considered as a differential in women presenting with features of heart failure in later months of pregnancy or within 5 months of delivery. [ABSTRACT FROM AUTHOR]

Objective To review experience regarding the treatment of prolactinomas by endoscopic endonasal surgery focusing on the association between presurgical dopamine agonist (DA) treatment and perioperative outcomes, surgical morbidities, endocrine outcomes, and pathological characteristics. Methods A single-center series of 290 cases was analyzed retrospectively and clinical data were collected. Intratumoral collagen content was assessed by Masson trichrome staining. Results Tenacious tumor consistency (27.8% vs 9.8%, P <.001) was more common in DA-pretreated patients compared with patients who underwent initial surgery. Moreover, DA-pretreated macroadenomas presented more intraoperative blood loss (200 [100-400] mL vs 175 [100-300] mL; P =.014), longer surgical duration (177 ± 95 minutes vs 154 ± 57 minutes; P =.043), and more surgical morbidities (19.4% vs 8.9%; P =.034). Additionally, DA-pretreated macroadenomas presented a higher collagen volume fraction than that of the initial surgery group (23.6 ± 2.2% vs 13.2 ± 2.1%; P =.001). Correlation analysis revealed a close correlation between collagen volume fraction and the cumulative dose of bromocriptine (BRC) in macroadenomas (r = 0.438, P <.001). Regarding endocrine outcomes, DA-pretreated microadenomas showed a lower proportion of initial remission compared with patients who underwent initial surgery (86.7% vs 100%, P =.047). Conclusion This study described increased surgical difficulty and inferior endocrine outcomes associated with tumor fibrosis secondary to presurgical BRC treatment in prolactinomas. Neurosurgeons should note that presurgical BRC treatment may render subsequent surgery more challenging. [ABSTRACT FROM AUTHOR]

Purpose: Prolactin (PRL)-secreting tumours are associated with infertility and can be reverted by dopamine agonist (DA) therapy. The suspension of DA is recommended once pregnancy is established, as all DAs cross the placenta. The aim of the study was to evaluate the rate of maternal-foetal complications in women treated with cabergoline (CAB) or bromocriptine (BRM) for prolactinoma during gestation and the effect of pregnancy on prolactinoma progression. Methods: This was a retrospective observational study involving 43 women affected by prolactinoma who became pregnant during therapy with CAB or BRM for a total of 58 pregnancies. For each patient, medical records were analysed by integrating the data with outpatient or telephone interview. Results: At the time of conception, 18 women were in the BRM group, while 40 were in CAB group. No differences were found in obstetric or neonatal outcomes between the two groups. There was a significant difference (p = 0.046) in child complications reported in maternal interview found exclusively in the CAB group. No further confounding factors were detected. Disease remission rate after the first pregnancy was 42.9% and the main predictor was a lower PRL nadir before pregnancy (p = 0.023). No difference was detected between the two groups in terms of tumor remission. Breastfeeding did not modify the outcome. Conclusion: Foetal exposure to DAs during the first weeks of embryogenesis is not associated with a greater risk of complications. The transient and mild developmental disorders recorded resolved spontaneously and the prevalence was substantially overlapping with that observed in the general population. [ABSTRACT FROM AUTHOR]

Abstract 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.

Pregnancy is a period in which the anatomy and physiology of the pituitary gland change significantly. Normal pituitary gland functions are necessary for fertility and the continuation of pregnancy. The presence of a pituitary disease requires management with a multidisciplinary approach to protect the health of the mother and fetus, and it is recommended that these patients become pregnant in a planned manner. Treatment should be considered before pregnancy for pituitary adenomas with a risk of growth. Non-contrast magnetic resonance imaging (MRI) may be performed safely during pregnancy, but the ideal approach is to postpone the MRI until after the birth if possible, and if it is not possible, to take it without contrast. If there are no signs of compression in pituitary adenomas, no treatment is necessary during pregnancy. However, due to increased fetal and maternal morbidity and mortality in Cushing’s disease, treatment is necessary even if there is no compression. In the presence of compression findings, dopamine agonists can be used in all types of pituitary adenomas. Surgery may be performed in the second trimester for pituitary adenomas that cause compression unresponsive to medical treatment and for Cushing’s disease. In pregnant women with pituitary insufficiency, replacement doses should be adjusted according to the gestational week. The diagnosis and treatment of pituitary diseases in this period is more complex and specific than in the nonpregnant period and require a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Chronic adipose tissue inflammation accompanied by macrophage accumulation and activation is implicated in the pathogenesis of insulin resistance and type 2 diabetes in humans. The transcriptional coregulator CREBZF is a key factor in hepatic metabolism, yet its role in modulating adipose tissue inflammation and type 2 diabetes remains elusive. The present study demonstrates that overnutrition‐induced CREBZF links adipose tissue macrophage (ATM) proinflammatory activation to insulin resistance. CREBZF deficiency in macrophages, not in neutrophils, attenuates macrophage infiltration in adipose, proinflammatory activation, and hyperglycemia in diet‐induced insulin‐resistant mice. The coculture assays show that macrophage CREBZF deficiency improves insulin sensitivity in primary adipocytes and adipose tissue. Mechanistically, CREBZF competitively inhibits the binding of IκBα to p65, resulting in enhanced NF‐κB activity. In addition, bromocriptine is identified as a small molecule inhibitor of CREBZF in macrophages, which suppresses the proinflammatory phenotype and improves metabolic dysfunction. Furthermore, CREBZF is highly expressed in ATM of obese humans and mice, which is positively correlated with proinflammatory genes and insulin resistance in humans. This study identifies a previously unknown role of CREBZF coupling ATM activation to systemic insulin resistance and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Impulse control disorders (ICDs) have been described as underrecognized side effects of dopamine agonists (DAs) in neurological disorders but are not sufficiently understood in endocrine conditions. Objective: To identify the prevalence of DAs induced ICDs and determine potential risk factors related to these disorders in patients with prolactinoma and non-function pituitary adenomas (NFPAs). Methods: This is a cross-sectional multicenter study involving 200 patients with prolactinoma and NFPAs, who received follow-ups in tertiary referral centers. DA-induced ICDs were assessed using ICD questionnaires modified from prior studies. Result: At least one ICD was reported by 52% of participants, among whom 28.5% mentioned compulsive shopping, 24.5% punding, and 24.5% hypersexuality. Furthermore, 33% of the patients reported the presence of one type of ICD behavior, while 12% specified two and 7% had three types of such behavior. The multivariable logistic regression showed that the significant risk factors of ICD were younger age (adjusted odds ratio [AOR]: 0.92, 95% confidence interval [CI]: 0.88–0.97, p 0.001), being single (AOR: 0.15, 95%CI: 0.03–0.84, p 0.03), and a positive history of psychiatric illness (AOR: 7.67, 95% CI: 1.37–42.97, p 0.021). Conclusion: ICDs with a broad range of psychiatric symptoms are common in individuals with DA-treated prolactinoma and NFPAs. Endocrinologists should be aware of this potential side effect, particularly in patients with a personal history of psychiatric disorder. [ABSTRACT FROM AUTHOR]

A series of well-described anabolic and catabolic neuropeptides are known to provide short-term, homeostatic control of energy balance. The mechanisms that govern long-term, rheostatic control of regulated changes in energy balance are less well characterized. Using the robust and repeatable seasonal changes in body mass observed in Siberian hamsters, this report examined the role of prolactin in providing long-term rheostatic control of body mass and photoinduced changes in organ mass (ie, kidney, brown adipose tissue, uterine, and spleen). Endogenous circannual interval timing was observed after 4 months in a short photoperiod, indicated by a significant increase in body mass and prolactin mRNA expression in the pituitary gland. There was an inverse relationship between body mass and the expression of somatostatin (Sst) and cocaine- and amphetamine-regulated transcript (Cart). Pharmacological inhibition of prolactin release (via bromocriptine injection), reduced body mass of animals maintained in long photoperiods to winter–short photoperiod levels and was associated with a significant increase in hypothalamic Cart expression. Administration of ovine prolactin significantly increased body mass 24 hours after a single injection and the effect persisted after 3 consecutive daily injections. The data indicate that prolactin has pleiotropic effects on homeostatic sensors of energy balance (ie, Cart) and physiological effectors (ie, kidney, BAT). We propose that prolactin release from the pituitary gland acts as an output signal of the hypothalamic rheostat controller to regulate adaptive changes in body mass. [ABSTRACT FROM AUTHOR]

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. 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. [ABSTRACT FROM AUTHOR]

Objectives: Prolactinoma is a common intracranial tumor with a high incidence and serious harm to human health. At present, there is only one therapeutic drug in China, bromocriptine, and the Chinese herb Prunella vulgaris L. (P. vulgaris)(PV) has shown certain anti-prolactinoma effects in the early stage. We expect to develop a candidate drug against prolactinoma. Materials and Methods: First, the extracts of P. vulgaris L.(PVE)were extracted with water, and the cell proliferation test of rat pituitary tumor cells MMQ was checked by the Cell Counting Kit-8 (CCK-8) assay. Then, core targets and correlative pathways were selected by the "protein–protein interaction" (PPI) network and the "PV–Target–Prolactinoma" network. The core targets and main components simulate the binding by molecular docking. Finally, the PVE and MMQ cells were used to verify the results. Results: Through the CCK-8 assay, the PVE inhibited the proliferation of MMQ cells. From the network pharmacology, the 21 targets, 9 signaling pathways, and 20 gene ontology (GO) projects were attained (p < 0.05). As a result the estrogen receptor α (ESR1), RAC-alpha serine/threonine-protein kinase(AKT1), and mitogen-activated protein kinase 3(MAPK3)were the core targets of protein against prolactinomas, which was in line with western blotting analysis. Conclusion: Our findings demonstrate that the PVE was verified against prolactinomas through the ESR1, MAPK3 targets, and the phosphoinositide 3-kinase/protein kinase B pathway. [ABSTRACT FROM AUTHOR]

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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT: Prolactinoma is a benign tumor of the pituitary gland that leads to the overproduction of prolactin. It is the most common type of pituitary adenoma, accounting for approximately 50% of all pituitary tumors. The clinical presentation of prolactinoma varies depending on the level of prolactin elevation and the size of the tumor. In women, common symptoms include galactorrhea, amenorrhea, and infertility. Men may present with hypogonadism, decreased libido, erectile dysfunction, and gynecomastia. Large prolactinomas, known as macroadenomas, can cause mass effects such as headaches, visual disturbances due to compression of the optic chiasm, and hypopituitarism due to pressure on surrounding pituitary tissue. Understanding the pathogenesis of prolactinoma is crucial for developing effective treatments and improving patient outcomes. The development of prolactinomas involves a complex interplay of genetic, hormonal, and cellular factors. Treatment of prolactinoma aims to normalize prolactin levels, reduce tumor size, and alleviate symptoms. The first-line therapy is dopamine agonists, such as cabergoline and bromocriptine, with surgery and radiotherapy reserved for refractory cases. Furthermore, chemotherapeutic agent - temozolomide may be a treatment of choice in aggressive or malignant prolactinomas. By understanding the underlying mechanisms and different treatment methods, healthcare providers can optimize the management and outcomes for patients with prolactinoma.

Key Clinical Message Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure associated with pregnancy without any other known cause. With a prognosis that can vary from the complete recovery of left ventricular function to maternal mortality as well as recurrence with subsequent pregnancies, early diagnosis and treatment of PPCM is important in management. Bromocriptine treatment is beneficial effects on LVEF and mortality in women with severe acute PPCM in addition to standard heart failure therapy. However, further study is required to establish its effect in PPCM. Abstract Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure associated with pregnancy without any other known cause. Most of the clinical presentation is similar to symptoms of advanced pregnancy making the diagnosis difficult. Reported are three patients who developed dyspnea, orthopnea, and dry cough during the first week of puerperium. On examination, bilateral lower limb edema and bilateral basal lung crepitation were present in all patients. Chest radiograph showed pulmonary edema in cases two and three, and pleural effusion in case one. All patients had reduced left ventricular ejection fraction and raised N‐terminal pro‐b‐type natriuretic peptide (NT‐proBNP) levels. Case two developed PPCM in the background of left pyelonephritis. Case three was complicated by acute kidney injury. All patients were managed with bromocriptine, diuretics, beta‐blockers, ACE inhibitors, and fluid restriction. Hence, PPCM though rare should be considered as a differential in women presenting with features of heart failure in later months of pregnancy or within 5 months of delivery.

Lipodystrophies involve the loss of subcutaneous adipose tissue, resulting in severe metabolic issues such as insulin resistance and challenging diabetes management. This case series aims to assess bromocriptine treatment response in lipodystrophy patients, offering insights into its antidiabetic effects. This retrospective analysis focused on four female lipodystrophy patients with poor glycemic control who were undergoing bromocriptine treatment. Statistical analysis used nonparametric tests. Metabolic parameters were assessed before and 3 months post-bromocriptine treatment, revealing a modest reduction in median daily insulin dose and decreased hemoglobin A1c and fasting glucose levels. Body weight remained constant, while triglyceride levels increased. Dopamine receptor expression in pancreatic ß-cells and adipocytes suggests a direct impact on glucose homeostasis. While this case series hints at bromocriptine's positive influence on glycemic control and insulin requirements in lipodystrophy patients, larger studies are essential for establishing efficacy and safety. [ABSTRACT FROM AUTHOR]

Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory disorder of the breast that is often underrecognized. The exact etiology and pathophysiology are unknown, but milk stasis is felt to play a role. Classically, this condition is noninfectious, but many cases are noted to be associated with Corynebacterium species. Most patients affected are parous women with a mean age of 35, and many have breastfed within five years of diagnosis. Patients typically present with a painful mass and symptoms of inflammation, and these features can sometimes mimic breast cancer. Biopsy is needed to make a definitive diagnosis, and noncaseating granulomas are found on core biopsy. Many patients have a waxing and waning course over a period of six months to two years. Goal of treatment is to avoid surgery given poor wound healing, high risk of recurrence, and poor cosmetic outcomes. Medical treatment is preferred and includes observation, antibiotics, steroids, and immune modulators such as methotrexate. In more recent years, topical and intralesional steroids have become the treatment of choice, with similar outcomes to oral steroids. [ABSTRACT FROM AUTHOR]

Peripartum cardiomyopathy (PPCM) is a form of heart failure, often severe, that occurs in previously healthy women at the end of their pregnancy or in the first few months after delivery. In PPCM, the recovery of heart function reaches 45–50%. However, the all-cause mortality in long-term observation remains high, reaching 20% irrespective of recovery status. The incidence of PPCM is increasing globally; therefore, effort is required to clarify the pathophysiological background of the disease, as well as to discover specific diagnostic and prognostic biomarkers. The etiology of the disease remains unclear, including oxidative stress; inflammation; hormonal disturbances; endothelial, microcirculatory, cardiomyocyte and extracellular matrix dysfunction; fibrosis; and genetic mutations. Currently, antiangiogenic 16-kDa prolactin (PRL), cleaved from standard 23-kDa PRL in the case of unbalanced oxidative stress, is recognized as the main trigger of the disease. In addition, 16-kDa PRL causes damage to cardiomyocytes, acting via microRNA-146a secreted from endothelial cells as a cause of the NF-κβ pathway. Bromocriptine, which inhibits the secretion of PRL from the pituitary gland, is now the only specific treatment for PPCM. Many different phenotypes of the disease, as well as cases of non-responders to bromocriptine treatment, indicate other pathophysiological pathways that need further investigation. Biomarkers in PPCM are not well established. There is a deficiency in specific diagnostic biomarkers. Pro-brain-type natriuretic peptide (BNP) and N-terminal BNP are the best, however unspecific, diagnostic biomarkers of heart failure at the moment. Therefore, more efforts should be engaged in investigating more specific biomolecules of a diagnostic and prognostic manner such as 16-kDa PRL, galectin-3, myeloperoxidase, or soluble Fms-like tyrosine kinase-1/placental growth factor ratio. In this review, we present the current state of knowledge and future directions of exploring PPCM pathophysiology, including microRNA and heat shock proteins, which may improve diagnosis, treatment monitoring, and the development of specific treatment strategies, and consequently improve patients' prognosis and outcome. [ABSTRACT FROM AUTHOR]

Contextual information is essential for learning and memory processes and plays a crucial role during the recall of extinction memory, and in the renewal effect, which is the context-dependent recovery of an extinguished response. The dopaminergic system is known to be involved in regulating attentional processes by shifting attention to novel and salient contextual cues. Higher dopamine levels are associated with a better recall of previously learned stimulus-outcome associations and enhanced encoding, as well as retrieval of contextual information which promotes renewal. In this fMRI study, we aimed to investigate the impact of processing contextual information and the influence of dopaminergic D2-like receptor activation on attention to contextual information during a predictive learning task as well as upon extinction learning, memory performance, and activity of extinction-related brain areas. A single oral dose of 1.25 mg bromocriptine or an identical-looking placebo was administered to the participants. We modified a predictive learning task that in previous studies reliably evoked a renewal effect, by increasing the complexity of contextual information. We analysed fixations and dwell on contextual cues by use of eye-tracking and correlated these with behavioural performance and BOLD activation of extinction-related brain areas. Our results indicate that the group with dopaminergic D2-like receptor stimulation had higher attention to task-relevant contextual information and greater/lower BOLD activation of brain regions associated with cognitive control during extinction learning and recall. Moreover, renewal responses were almost completely absent. Since this behavioural effect was observed for both treatment groups, we assume that this was due to the complexity of the altered task design. [ABSTRACT FROM AUTHOR]

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.

Bromocriptine (BCR) presents poor bioavailability when administered orally because of its low solubility and prolonged first-pass metabolism. This poses a significant challenge in its utilization as an effective treatment for managing Parkinson’s disease (PD). The utilization of lipid nanoparticles can be a promising approach to overcome the limitations of BCR bioavailability. The aim of the research work was to develop and evaluate bromocriptine-loaded solid lipid nanoparticles (BCR-SLN) and bromocriptine-loaded nanostructured lipid carriers (BCR-NLC) employing the Box-Behnken design (BBD). BCR-SLNs and BCR-NLCs were developed using the high-pressure homogenization method. The prepared nanoparticles were characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE). In vitro drug release, cytotoxicity studies, in vivo plasma pharmacokinetic, and brain distribution studies evaluated the optimized lipid nanoparticles. The optimized BCR-SLN had a PS of 219.21 ± 1.3 nm, PDI of 0.22 ± 0.02, and EE of 72.2 ± 0.5. The PS, PDI, and EE of optimized BCR-NLC formulation were found to be 182.87 ± 2.2, 0.16 ± 0.004, and 83.57 ± 1.8, respectively. The in vitro release profile of BCR-SLN and BCR-NLC showed a biphasic pattern, immediate release, and then trailed due to the sustained release. Furthermore, a pharmacokinetic study indicated that both the optimized BCR-SLN and BCR-NLC formulations improve the plasma and brain bioavailability of the drug compared to the BCR solution. Based on the research findings, it can be concluded that the BCR-loaded lipid nanoparticles could be a promising carrier by enhancing the BBB penetration of the drug and helping in the improvement of the bioavailability and therapeutic efficacy of BCR in the management of PD.

Abstract Background Type 2 diabetes (T2DM) patients, including those in good glycemic control, have an increased risk of cardiovascular disease (CVD). Maintaining good glycemic control with drugs may reduce long-term CVD risk. Bromocriptine has been in clinical use for over 30 years, but the utility of bromocriptine in the treatment of diabetes patients has been proposed more recently. Objective To summarize the available data regarding the effect of bromocriptine in T2DM management. Method A systematic literature search was conducted in the electronic databases, including Google Scholar, PubMed, Medline, and Science Direct, to locate studies that meet the objectives of this systematic review. Additional articles were included by conducting direct Google searches of the references cited by eligible articles located by the database search. The following search terms were used on PubMed “bromocriptine OR dopamine agonist AND diabetes mellitus OR hyperglycemia OR obese”. Result Eight studies were included in the final analysis. 6210 of the 9391 study participants received bromocriptine treatment, while 3183 received a placebo. The studies demonstrated that patients who took bromocriptine treatment had significantly reduced blood glucose and BMI, which is the main cardiovascular risk factor in T2DM patients. Conclusion Based on this systematic review, bromocriptine may be used for T2DM treatment for its cardiovascular risk reduction effect, especially body weight reduction. However, advanced study designs might be warranted.

Abstract Background Giant prolactinoma (> 4 cm in dimension) is a rare disorder. Invasive macroprolactinoma has the potential to cause base of skull erosion and extend into the nasal cavity or even the sphenoid sinus. Nasal bleeding caused by intranasal tumor extension is a rare complication associated with invasive giant prolactinoma. We report a case of giant invasive macroprolactinoma with repeated nasal bleeding as the initial symptom. Case presentation A 24-year-old man with an invasive giant prolactinoma in the nasal cavity and sellar region who presented with nasal bleeding as the initial symptom, misdiagnosed as olfactory neuroblastoma. However, markedly elevated serum prolactin levels (4700 ng/mL), and a 7.8-cm invasive sellar mass confirmed the diagnosis of invasive giant prolactinoma. He was treated with oral bromocriptine. Serum prolactin was reduced to near normal after 6 months of treatment. Follow-up magnetic resonance imaging showed that the sellar lesion had disappeared completely and the skull base lesions were reduced. Conclusion This case is notable in demonstrating the aggressive nature of untreated invasive giant prolactinomas which can cause a diagnostic difficulty with potential serious consequences. Early detection of hormonal levels can avoid unnecessary nasal biopsy. Early identification of pituitary adenoma with nasal bleeding as the first symptom is particularly important.

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma. Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies. Methods: The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure’s specific drivers that contributed to its total cost. Results: The average cost of the first year of treatment was €2,558.91 and €3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were €798.13 and €1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of €3,201.15 compared to bromocriptine, based on a willingness-to-pay of €40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of €44,846.64. Considering a willingness-to-pay of €40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that. Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources.

Introduction: The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. Strategies to decrease this risk should be strongly encouraged. Lactation has been associated, for the mother, with reduction in future T2DM risk in several studies. The mechanisms behind this phenomenon, however, are poorly understood. The aims of this study were, first, to compare blood glucose levels and markers of insulin resistance (MIR) in early postpartum women with overweight/obesity according to their breastfeeding status and, second, to evaluate whether prolactin (PRL) levels could mediate improvements in these parameters. Methods: The prospective study followed 95 women older than 18 years from early pregnancy for up to 60 to 180 days postpartum. All participants had a BMI > 25 kg/m2 and a singleton pregnancy. At each visit, questionnaires and clinical and biochemical evaluations were performed. Participants were divided into two groups according to the breastfeeding status as “yes” for exclusive or predominant breastfeeding, and “no” for not breastfeeding. Results: Breastfeeding women (n = 44) had significantly higher PRL levels [47.8 (29.6–88.2) vs. 20.0 (12.0–33.8), p< 0.001]. They also had significantly lower fasting blood glucose levels [89.0 (8.0) vs. 93.9 (12.6) mg/dl, p = 0.04], triglycerides (TG) [92.2 (37.9) vs. 122.4 (64.4) mg/dl, p = 0.01], TG/HDL ratio [1.8 (0.8) vs. 2.4 (1.6) mg/dl, p = 0.02], TyG index [8.24 (0.4) vs. 8.52 (0.53), p = 0.005], fasting serum insulin [8.9 (6.3–11.6) vs. 11.4 (7.7–17.0), p = 0.048], and HOMA-IR [2.0 (1.3–2.7) vs. 2.6 (1.6–3.9), p = 0.025] in the postpartum period compared to the non-breastfeeding group. Groups were homogeneous in relation to prevalence of GDM, pre-gestational BMI, as well as daily caloric intake, physical activity, and weight loss at postpartum. Linear regression analysis with adjustments for confounders showed a statistically significant association of reastfeeding with fasting blood glucose [−6.37 (−10.91 to −1.83), p = 0.006], HOMA-IR [−0.27 (−0.51 to −0.04), p = 0.024], TyG index [−0.04 (−0.06 to −0.02), p = 0.001], and TG/HDL ratio [−0.25 (−0.48 to −0.01), p = 0.038]. Mediation analysis showed that PRL did not mediate these effects. Sensitivity analyses considering different cutoffs for PRL levels also did not show modification effect in the mediation analyses. Conclusion: Breastfeeding was associated with improvement in glucose metabolism and MIR 60 to 180 days after birth in overweight and obese women, even when adjusted for confounders. PRL levels were not found to mediate the association between breastfeeding and improvement in MIR. [ABSTRACT FROM AUTHOR]

Background: 'Central' fevers are thought to result from disruption of hypothalamic thermoregulatory pathways following severe brain injuries. Bromocriptine, due to its central dopamine receptor agonism, has been hypothesized to have antipyretic effect in this setting. However, clinical evidence for this off-label use is limited to a few case reports. In this retrospective cohort study, we analyzed the effect of bromocriptine administration on body temperature in acute brain injury patients with suspected central fever. Methods: We screened a cohort of adult patients that received bromocriptine in the neurologic-intensive care unit of a tertiary care hospital between January 2018 and December 2021. Indication of central fever was ascertained by review of clinical documentation. A generalized additive mixed model (GAMM) was used to model temperature as a function of time relative to bromocriptine initiation. We adjusted for potential confounding due to the following covariates: temperature recording method (invasive vs surface), concurrent antipyretic administration within 8 h, and surface cooling device use within 4 h of temperature measurement. Temperature–time function was modeled using a cubic spline with k = 10 knots. Results: A total of 33 patients were included in the analysis (14 women; mean age: 50 y, standard deviation 14 y). Median dose of bromocriptine was 7.5 mg (range 2.5–40) for a median of 13 d (range 5–160). Age and sex did not impact the function of temperature over time. Predicted temperatures were significantly (p < 0.05) higher by 0.4 °C with invasive compared to surface recording methods, lower by 0.2 °C in the presence of cooling device use and lower by 0.1 °C with concurrent antipyretic use. On adjusted analysis with the GAMM, there was decline (p < 0.05) in temperature following bromocriptine initiation by − 0.3 °C at 24 h, − 0.5 °C at 48 h, and − 0.7 °C at 72 h. Conclusions: Bromocriptine use was associated with modest but statistically significant decline in temperature, with nadir at 72 h post initiation. The findings provide a data driven basis for prospective evaluation. [ABSTRACT FROM AUTHOR]

Despite enormous global efforts within clinical research and medical practice to reduce cardiovascular disease(s) (CVD), it still remains the leading cause of death worldwide. While genetic factors clearly contribute to CVD etiology, the preponderance of epidemiological data indicate that a major common denominator among diverse ethnic populations from around the world contributing to CVD is the composite of Western lifestyle cofactors, particularly Western diets (high saturated fat/simple sugar [particularly high fructose and sucrose and to a lesser extent glucose] diets), psychosocial stress, depression, and altered sleep/wake architecture. Such Western lifestyle cofactors are potent drivers for the increased risk of metabolic syndrome and its attendant downstream CVD. The central nervous system (CNS) evolved to respond to and anticipate changes in the external (and internal) environment to adapt survival mechanisms to perceived stresses (challenges to normal biological function), including the aforementioned Western lifestyle cofactors. Within the CNS of vertebrates in the wild, the biological clock circuitry surveils the environment and has evolved mechanisms for the induction of the obese, insulin-resistant state as a survival mechanism against an anticipated ensuing season of low/no food availability. The peripheral tissues utilize fat as an energy source under muscle insulin resistance, while increased hepatic insulin resistance more readily supplies glucose to the brain. This neural clock function also orchestrates the reversal of the obese, insulin-resistant condition when the low food availability season ends. The circadian neural network that produces these seasonal shifts in metabolism is also responsive to Western lifestyle stressors that drive the CNS clock into survival mode. A major component of this natural or Western lifestyle stressor-induced CNS clock neurophysiological shift potentiating the obese, insulin-resistant state is a diminution of the circadian peak of dopaminergic input activity to the pacemaker clock center, suprachiasmatic nucleus. Pharmacologically preventing this loss of circadian peak dopaminergic activity both prevents and reverses existing metabolic syndrome in a wide variety of animal models of the disorder, including high fat-fed animals. Clinically, across a variety of different study designs, circadian-timed bromocriptine-QR (quick release) (a unique formulation of micronized bromocriptine—a dopamine D2 receptor agonist) therapy of type 2 diabetes subjects improved hyperglycemia, hyperlipidemia, hypertension, immune sterile inflammation, and/or adverse cardiovascular event rate. The present review details the seminal circadian science investigations delineating important roles for CNS circadian peak dopaminergic activity in the regulation of peripheral fuel metabolism and cardiovascular biology and also summarizes the clinical study findings of bromocriptine-QR therapy on cardiometabolic outcomes in type 2 diabetes subjects. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular diseases are a primary cause of morbidity and mortality during the peripartum period. Peripartum cardiomyopathy (PPCM) is classified as idiopathic cardiomyopathy that manifest with heart failure (HF) symptoms due to left ventricle (LV) dysfunction by the end of the pregnancy or the early postpartum period in absence of any other identifiable cause of HF. The objective of this study is to assess the risk factors associated with PPCM and to share our knowledge regarding diagnostic approaches, treatment modalities and follow up outcomes for patients diagnosed with PPCM. Material and methods: A prospective study including 22 women with an average parturition age of 31.82 years who were diagnosed with PPCM either during pregnancy or within 6 months postpartum has been conducted between 2003 and 2023. These patients have been chronologically divided into two groups. Group 1 consisted of 18 patients (81.82%) with HF symptoms and group 2 comprised 4 patients with HF undergoing Bromocriptine treatment. Comprehensive examinations have been performed on all patients by a cardiologist including ECG, ambulatory Holter ECG monitoring, echocardiography and blood test. Cardiovascular risk has been stratified both during the pregnancy and after delivery. All patients received treatment and have been subsequently monitored in terms of survival and mortality rates. Results: The most common risk factors for PPCM include: preeclampsia, hypertension, HELLP syndrome, arrhythmias and pregnancy in women over 31 years of age. A majority of patients (73%) have been diagnosed with PPCM five months postpartum, with 9 of them (40.1%) having an acute onset of the disease. The mortality rate stands at 16.66%. Treatment with bromocriptine has shown significant improvement in follow up outcomes. Conclusion: PPCM is a rare condition in Bulgaria characterized by diverse progression and high morbidity and mortality rates. For individuals with history of cardiomyopathy, onset of HF symptoms, arrhythmias both prior to and during pregnancy, it is advisable to undergo evaluation by cardiologist. This should be followed by initiation of appropriate treatment and the establishment of a comprehensive monitoring regimen throughout pregnancy and postpartum period. [ABSTRACT FROM AUTHOR]