Cabergoline, prolactin and heart

Summary Introduction and aim:  Dopamine agonists have been reported to increase the risk of cardiac valve regurgitation in patients with Parkinson's disease. However, it is unknown whether these drugs might be harmful for patients with hyperprolactinaemia (HyperPRL). The aim of the study was to evaluate whether HyperPRL patients treated with dopamine agonists had a higher prevalence of cardiac valves regurgitation than that of general population. Methods and patients:  One hundred consecutive patients (79 women, 21 men, mean age 41 ± 13 years) with HyperPRL during treatment with cabergoline were enrolled in an observational case–control study and compared with 100 matched normal subjects (controls). Valve regurgitation was assessed by echocardiography according to the American Society of Echocardiography recommendations. Results:  Seven HyperPRL patients (7%) and six controls (6%) had moderate (grade 3) regurgitation in any valve (p = 0.980). All were asymptomatic and had no signs of cardiac disease. Mean duration of cabergoline treatment was 67 ± 39 months (range: 3–199 months). Mean cumulative dose of cabergoline was 279 ± 301 mg (range: 15–1327 mg). Moderate valve regurgitation was not associated with the duration of treatment (p = 0.359), with cumulative dose of cabergoline (p = 0.173), with age (p = 0.281), with previous treatment with bromocriptine (p = 0.673) or previous adenomectomy (p = 0.497) in patients with HyperPRL. Discussion:  In conclusion, treatment with cabergoline was not associated with increased prevalence of cardiac valves regurgitation in patients with HyperPRL. Mean cumulative dose of cabergoline was lower in patients with HyperPRL than that reported to be deleterious for patients with Parkinson's disease: hence, longer follow-up is necessary, particularly in patients receiving weekly doses > 3 mg

Hydrogen blending effect on fiscal and metrological instrumentation: A review

A green hydrogen (H2) economy requires a sustainable, efficient, safe, and widespread infrastructure for transporting and distributing H2 from production to consumption sites. Transporting a hydrogen/natural gas (H2NG) mixture, including pure H2, through the existing European natural gas (NG) infrastructure is considered a cost-effective solution, particularly in the transitional phase. Several reasons justify the H2NG blending option. The NG infrastructure can be efficiently repurposed to transport H2, by blending H2 with NG, to operate as H2 daily storage, matching production and demand and to enable large-scale seasonal H2 storage. Although many benefits exist, the potential of existing NG grids for transporting and distributing green H2 may face limitations due to technical, economic, or normative concerns. This paper focuses on the state of the art of the European NG transmission and distribution metrology normative framework and identifies the gaps to be filled in case of H2NG flowing into the existing grids. The paper was revised to provide a comprehensive analysis of the practical implications resulting from the H2NG blend option

Inositol-triphosphate 3-kinase B promotes calcium mobilization and the inflammatory activity of dendritic cells.

peer reviewedInnate immune responses to Gram-negative bacteria depend on the recognition of lipopolysaccharide (LPS) by a receptor complex that includes CD14 and TLR4. In dendritic cells (DCs), CD14 enhances the activation not only of TLR4 but also that of the NFAT family of transcription factors, which suppresses cell survival and promotes the production of inflammatory mediators. NFAT activation requires Ca2+ mobilization. In DCs, Ca2+ mobilization in response to LPS depends on phospholipase C γ2 (PLCγ2), which produces inositol 1,4,5-trisphosphate (IP3). Here, we showed that the IP3 receptor 3 (IP3R3) and ITPKB, a kinase that converts IP3 to inositol 1,3,4,5-tetrakisphosphate (IP4), were both necessary for Ca2+ mobilization and NFAT activation in mouse and human DCs. A pool of IP3R3 was located on the plasma membrane of DCs, where it colocalized with CD14 and ITPKB. Upon LPS binding to CD14, ITPKB was required for Ca2+ mobilization through plasma membrane-localized IP3R3 and for NFAT nuclear translocation. Pharmacological inhibition of ITPKB in mice reduced both LPS-induced tissue swelling and the severity of inflammatory arthritis to a similar extent as that induced by the inhibition of NFAT using nanoparticles that delivered an NFAT-inhibiting peptide specifically to phagocytic cells. Our results suggest that ITPKB may represent a promising target for anti-inflammatory therapies that aim to inhibit specific DC functions