Background: Supplementation of calcium during continuous venovenous hemofiltration (CVVH) with citrate anticoagulation is usually titrated using a target blood ionized calcium concentration. Plasma... Show moreBackground: Supplementation of calcium during continuous venovenous hemofiltration (CVVH) with citrate anticoagulation is usually titrated using a target blood ionized calcium concentration. Plasma calcium concentrations may be normal despite substantial calcium loss, by mobilization of calcium from the skeleton. Aim of our study is to develop an equation to calculate CVVH calcium and to retrospectively calculate CVVH calcium balance in a cohort of ICU-patients. Methods: This is a single-center retrospective observational cohort study. In a subcohort of patients, all calcium excretion measurements in patients treated with citrate CVVH were randomly divided into a development set (n = 324 in 42 patients) and a validation set (n = 441 in 42 different patients). Using mixed linear models, we developed an equation to calculate calcium excretion from routinely available parameters. We retrospectively calculated calcium balance in 788 patients treated with citrate CVVH between 2014 and 2021. Results: Calcium excretion (mmol/24 h) was - 1.2877 + 0.646*[Ca](blood,total) * ultrafiltrate (l/24 h) + 0.107*blood flow (ml/h). The mean error of the estimation was - 1.0 +/- 6.7 mmol/24 h, the mean absolute error was 4.8 +/- 4.8 mmol/24 h. Calculated calcium excretion was 105.8 +/- 19.3 mmol/24 h. Mean daily CVVH calcium balance was - 12.0 +/- 20.0 mmol/24 h. Mean cumulative calcium balance ranged from - 3687 to 448 mmol. Conclusion: During citrate CVVH, calcium balance was negative in most patients, despite supplementation of calcium based on plasma ionized calcium levels. This may contribute to demineralization of the skeleton. We propose that calcium supplementation should be based on both plasma ionized calcium and a simple calculation of calcium excretion by CVVH.[GRAPHICS]. Show less
The experimental research in this thesis aims to gain more understanding of how the SCN network is organized and what is needed for network changes. More specifically, this work focused on the... Show moreThe experimental research in this thesis aims to gain more understanding of how the SCN network is organized and what is needed for network changes. More specifically, this work focused on the potential role of GABA and the GABAeric E/I balance in SCN network plasticity. Communication and synchronization in the SCN are important for the generation of a strong and coherent output signal. Under certain conditions, like long photoperiod, the phases of the individual SCN cells are more dispersed over the 24 hour cycle as evidenced by measurements of electrical activity and clock gene expression. Aging is also known to affect the network organization of the SCN with deterioration in synchronization among the individual SCN neurons. In this thesis, I present work that contributes to research questions regarding the effect of light exposure and/or aging on several characteristics of SCN network plasticity. Show less
Calcium is the third most abundant metal on earth, and the fundaments of its homeostasis date back to pre-eukaryotic life forms. In higher organisms, Ca2+ serves as a cofactor for a wide array of ... Show moreCalcium is the third most abundant metal on earth, and the fundaments of its homeostasis date back to pre-eukaryotic life forms. In higher organisms, Ca2+ serves as a cofactor for a wide array of (enzymatic) interactions in diverse cellular contexts and constitutes the most important signaling entity in excitable cells. To enable responsive behavior, cytosolic Ca2+ concentrations are kept low through sequestration into organellar stores, particularly the endoplasmic reticulum (ER), but also mitochondria and lysosomes. Specific triggers are then used to instigate a local release of Ca2+ on demand. Here, communication between organelles comes into play, which is accomplished through intimate yet dynamic contacts, termed membrane contact sites (MCSs). The field of MCS biology in relation to cellular Ca2+ homeostasis has exploded in recent years. Taking advantage of this new wealth of knowledge, in this Review, we invite the reader on a journey of Ca2+ flux through the ER and its associated MCSs. New mechanistic insights and technological advances inform the narrative on Ca2+ acquisition and mobilization at these sites of communication between organelles, and guide the discussion of their consequences for cellular physiology. Show less
Engberink, A.H.O.O.; Meijer, J.H.; Michel, S. 2018
Many organisms have developed an internal clock to cope with the daily and seasonal cycles in the environment. In mammals, suprachiasmatic nuclei (SCN) of the hypothalamus control circadian rhythms... Show moreMany organisms have developed an internal clock to cope with the daily and seasonal cycles in the environment. In mammals, suprachiasmatic nuclei (SCN) of the hypothalamus control circadian rhythms in behavior and physiology. Evidence links the proper function of circadian clock to mental and physical health. Aging disturbs the accurate function of the SCN and impairs many rhythms such as sleep-wake cycle. Hence improvement of clock function can aid healthy aging. In chapters 3 and 4 I show the ensemble output of the SCN neuronal network is more robust than individual cells__ output suggesting a compensatory role of the network in aging. Seasonal changes affect the physiology and reproduction success of many organisms. The SCN encodes for day-length by adjusting the pattern of its electrical activity rhythm.. In chapters 5 and 6 I reveal that plasticity in interneuronal and cell-intrinsic functions in the SCN helps the organism to adjust to yearly natural changes in photoperiod. These results imply that extensive artificial light in modern society may alter neurotransmitters action in the SCN. A better understanding of SCN network function and cellular properties facilitate alleviation of modern life-related diseases caused by circadian disturbances and aging. Show less
Silva, S.L. da; Vellas, B.; Elemans, S.; Luchsinger, J.; Kamphuis, P.; Yaffe, K.; ... ; Stijnen, T. 2014
The main objective of this thesis was to clarify the observed reversal of effect of classical risk factors for dementia and mortality with increasing age and to gain better insight in the... Show moreThe main objective of this thesis was to clarify the observed reversal of effect of classical risk factors for dementia and mortality with increasing age and to gain better insight in the biological mechanism behind the relation between both phenotypic and genetic variation in apolipoprotein E (apoE) and cognitive function. Although high cholesterol levels in midlife associate with worse cognitive function and dementia in late-life, this association attenuates and even reverses with increasing age. In memory outpatient clinic patients high blood pressure associated with better cognitive function, only in patients with structural brain damage. In the Leiden 85-Plus Study, a decline in global cognitive function preceded declines in total cholesterol levels, HDL cholesterol levels, and blood pressure, and not vice versa. Moreover, mortality was associated with larger declines in body mass index, total cholesterol levels, HDL cholesterol levels, and blood pressure. High plasma apoE levels associated with worse cognitive function, whereas offspring from Alzheimer__s disease patients had lower plasma apoE levels when measured in midlife compared to offspring from cognitively intact controls. Finally, high serum calcium levels were strongly associated with worse cognitive function in APOE _3_4 carriers, to a lesser extent in _3_3 carriers, but not in _2_3 carriers. Show less
Plant architecture is determined by tightly regulated developmental processes that largely depend on the action of the plant hormone auxin. A major determinant in auxin action, besides its... Show morePlant architecture is determined by tightly regulated developmental processes that largely depend on the action of the plant hormone auxin. A major determinant in auxin action, besides its signaling pathway, is its polar cell-to-cell transport (PAT) throughout the plant. The direction on this transport depends on the localization of the auxin efflux carriers, the PIN proteins. The PINOID (PID) serine/threonine protein kinase is a key regulator of the subcellular localization of the PINs, which are direct phosphorylation targets of the kinase. This thesis describes the functional analysis of three direct interacting partners of PID, two calcium-binding proteins, TOUCH3 (TCH3) and PID BINDING PROTEIN1 (PBP1), and a BTB and TAZ domain (BT) protein. Several studies have already indicated that calcium signaling is induced by auxin application and is necessary for auxin transport. With the isolation of the two calcium-binding proteins TCH3 and PBP1 as interactors of PID, a molecular link between auxin transport and calcium signaling was identified. In this thesis, we show that calcium is involved in the regulation of both the kinase activity and the subcellular localization of PID. In complement to calcium, BTB scaffold proteins are part of the PID protein complex. A detailed analysis of BT protein family in Arabidopsis indicate a functional redundancy among the five members of this family and their requirement for the female gametophyte development. Moreover the BT proteins are required scaffold components in the PID signaling pathway. The functional analyses of the PBPs described in this thesis uncover a new mechanism of protein kinase activity regulation via calcium signaling, and present novel roles for the BT proteins, not only in PID signaling, but also more in general in plant development. Show less
