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Sympathetic stimulation can compensate for hypocalcaemia-induced bradycardia in human and rabbit sinoatrial node cells
Get PDFRegular activation of the heart originates from cyclic spontaneous depolarisations of sinoatrial node cells (SANCs). Variations in electrolyte levels, commonly observed in haemodialysis (HD) patients, and the autonomic nervous system (ANS) profoundly affect the SANC function. Thus we investigated the effects of hypocalcaemia and sympathetic stimulation on the SANC beating rate (BR). The β-adrenergic receptor (β-AR) signalling cascade, as described by Behar et al., was incorporated into the SANC models of Severi et al. (rabbit) and Fabbri et al. (human). Simulations were conducted across various extracellular calcium ([Ca2+]o) (0.6-1.8 mM) and isoprenaline concentrations [ISO] (0-1000 nM) for a sufficient period of time to allow transient oscillations to equilibrate and reach a limit cycle. The β-AR cell response of the extended models was validated against new Langendorff-perfused rabbit heart experiments and literature data. The extended models revealed that decreased [Ca2+]o necessitated an exponential-like increase in [ISO] to restore the basal BR. Specifically at 1.2 mM [Ca2+]o, the Severi and Fabbri models required 28.0 and 9.6 nM [ISO], respectively, to restore the initial BR. Further reduction in [Ca2+]o to 0.6 mM required 170.0 and 43.6 nM [ISO] to compensate for hypocalcaemia. A sudden loss of sympathetic tone at low [Ca2+]o resulted in a loss of automaticity within seconds. These findings suggest that hypocalcaemic bradycardia can be compensated for by an elevated sympathetic tone. The integration of the β-AR pathways led to a logarithmic BR increase and offers insights into potential pathomechanisms underlying sudden cardiac death (SCD) in HD patients. KEY POINTS: We extended the sinoatrial node cell (SANC) models of Severi et al. (rabbit) and Fabbri et al. (human) using the β-adrenergic receptor (β-AR) signalling cascade Behar et al. described. Simulations were conducted across various extracellular calcium ([Ca2+]o) (0.6-1.8 mM) and isoprenaline concentrations [ISO] (0-1000 nM) to reflect conditions in haemodialysis (HD) patients. An exponential-like increase in [ISO] compensated for hypocalcaemia-induced bradycardia in both models, whereas interspecies differences increased the sensitivity of the extended Fabbri model towards hypocalcaemia and increased sympathetic tone. The extended models may help to further understand the pathomechanisms of several cardiovascular diseases affecting pacemaking, such as the high occurrence of sudden cardiac death (SCD) in chronic kidney disease (CKD) patients
Effect of non-spherical shape of dry powder aerosol drugs on their airway deposition distribution
Get PDFIn the majority of aerosol drug deposition modelling efforts, the particles are approximated by regular spheres. However, microscope images acquired after drug formulation available in the open literature suggest that their shape is not regular in most cases. This work aimed to combine experimental measurements and numerical simulations to reveal the shape factors of the particles of commercialized aerosol drugs and the effect of non-sphericity on the lung deposition distribution of these drugs. Aerosol particles of Bretaris Genuair, Buventol Easyhaler and Trelegy Ellipta were collected on the stages of a Next Generation Impactor after their emission from the dry powder inhalers. The samples were analyzed using scanning electron microscopy techniques. Aspect ratios and dynamic shape factors characteristic of particles in the size fractions representing each impactor stage were determined. Computer modelling of their airway deposition was performed by both neglecting and considering their irregular shape. The results of particle size measurements revealed that there was no size-specific shape factor of the particles, as they could be well characterized by a global shape factor. Although there was some inter-drug difference in terms of shape factors, the values were quite close to unity (usually between 1.02 and 1.06), except for the fiber-shaped particles representing a minority in the composition of Trelegy Ellipta, which could be characterized by shape factors of around 1.6. The results of computer simulations of deposition distribution indicate that neglecting the irregular shape does not lead to a major distortion of the simulation results unless fiber-shaped particles are also present after the formulation. Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved
Kódolt üzenetek dekódolása – A szubjektív ápolási diagnózisalkotás szempontrendszerének alkalmazása a gyakorlatban [Decoding Encoded Messages – Application of the Subjective Nursing Diagnosis Formulation Criteria in Practice]
Get PDFGlobal, regional, and national burden of suicide, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021
Get PDFGenetic and Seasonal Factors Influence Pungent Pepper Capsaicinoid and Vitamin C Content
Get PDFPungent red peppers and chilis are healthy foods and crucial ingredients of modern diets due to their content of bioactive phytochemicals such as carotenoids, tocopherols, capsaicinoids, polyphenols, and vitamin C. The production of pungent peppers with outstanding nutritional properties is influenced by genetic factors and their interaction with the environments where they are cultivated. This study was conducted to investigate the effects of genotype and climate conditions on the response of capsaicinoids and vitamin C. The extracts of pungent materials and vitamin C were separated and qualitatively determined by HPLC alone or hyphenated with mass spectroscopy. Four genotypes were selected and cultivated under traditional agricultural practices in southern Hungary. The yield properties and the contents of capsaicinoids and vitamin C were significantly influenced by genetic factors and, to a high extent, by the interaction between genotype × environment. The highest yield of 2.86 ± 0.59 kg/m2 was recorded for the CS variety. The yield was significantly decreased under high precipitation and low air temperature. The highest concentration of capsaicin of 1586–1734 µg/g dwt was found in the BHJ variety. The lowest level of 514 µg/g dwt of capsaicin was determined in the CS variety, in which the content significantly increased to 772 µg/g dwt with the increase in rainfall and decrease in air temperature in the warmer season of 2022. In most cultivars examined, capsaicin content negatively responded to the change of the climate toward higher precipitation and lower temperature except for SZ178, in which the concentration of capsaicinoids stayed insignificantly varied. The amount of vitamin C ranged between 570 and 135 µg/g dwt, with the highest content being in the BHJ and the lowest in the REK variety. In most varieties except the REK, vitamin C positively responded to a high and negatively to the reduced levels of precipitation. In conclusion, the phytochemical components of hot peppers respond differently to climatic factors—such as high rainfall, elevated air temperature, and intense sunlight—depending on the genotype’s ability to adapt to environmental changes
Értékek ébresztése : Gondolatok Csepeli György azonos című könyvétől ihletve
Get PDFHa az értékek nem ébrednek, nem támadnak fel, akkor soha nem látott katasztrófába rohan az emberiség. A Magyar Szociológiai Társaság volt elnökea társadalmi együttélés alapkérdéseit társadalom-lélektani, szociológiai és filozófiai alapokon vizsgálja 2023-ban megjelent művében. Csepeli György Értékekébresztése című könyvének recenziója az Isten utáni iszonytató űrről: korunkkihívásairól és a lehetséges megoldásokról
