326 results on '"Kerkhofs M"'
Search Results
152. Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics.
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Carreras-Sureda A, Jaña F, Urra H, Durand S, Mortenson DE, Sagredo A, Bustos G, Hazari Y, Ramos-Fernández E, Sassano ML, Pihán P, van Vliet AR, González-Quiroz M, Torres AK, Tapia-Rojas C, Kerkhofs M, Vicente R, Kaufman RJ, Inestrosa NC, Gonzalez-Billault C, Wiseman RL, Agostinis P, Bultynck G, Court FA, Kroemer G, Cárdenas JC, and Hetz C
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- Animals, Calcium metabolism, Calcium Signaling genetics, Endoplasmic Reticulum genetics, Inositol 1,4,5-Trisphosphate Receptors genetics, Mice, Mice, Knockout, Mitochondria genetics, Endoplasmic Reticulum metabolism, Endoribonucleases genetics, Energy Metabolism, Mitochondria metabolism, Protein Serine-Threonine Kinases genetics
- Abstract
Mitochondria-associated membranes (MAMs) are central microdomains that fine-tune bioenergetics by the local transfer of calcium from the endoplasmic reticulum to the mitochondrial matrix. Here, we report an unexpected function of the endoplasmic reticulum stress transducer IRE1α as a structural determinant of MAMs that controls mitochondrial calcium uptake. IRE1α deficiency resulted in marked alterations in mitochondrial physiology and energy metabolism under resting conditions. IRE1α determined the distribution of inositol-1,4,5-trisphosphate receptors at MAMs by operating as a scaffold. Using mutagenesis analysis, we separated the housekeeping activity of IRE1α at MAMs from its canonical role in the unfolded protein response. These observations were validated in vivo in the liver of IRE1α conditional knockout mice, revealing broad implications for cellular metabolism. Our results support an alternative function of IRE1α in orchestrating the communication between the endoplasmic reticulum and mitochondria to sustain bioenergetics.
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- 2019
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153. Therapeutic implications of novel peptides targeting ER-mitochondria Ca 2+ -flux systems.
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Kerkhofs M, Bultynck G, Vervliet T, and Monaco G
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- Animals, Endoplasmic Reticulum metabolism, Humans, Mitochondria metabolism, Peptides therapeutic use, Calcium metabolism, Calcium Signaling drug effects, Endoplasmic Reticulum drug effects, Mitochondria drug effects, Peptides pharmacology
- Abstract
Intracellular Ca
2+ -flux systems located at the ER-mitochondrial axis govern mitochondrial Ca2+ balance and cell fate. Multiple yet incurable pathologies are characterized by insufficient or excessive Ca2+ fluxes toward the mitochondria, in turn leading to aberrant cell life or death dynamics. The discovery and ongoing molecular characterization of the main interorganellar Ca2+ gateways have resulted in a novel class of peptide tools able to regulate relevant protein-protein interactions (PPIs) underlying this signaling scenario. Here, we review peptides, molecularly derived from Ca2+ -flux systems or their accessory proteins. We discuss how they alter Ca2+ -signaling protein complexes and modulate cell survival in light of their forthcoming therapeutic applications., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2019
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154. Recent advances in uncovering the mechanisms contributing to BIRD-2-induced cell death in B-cell cancer cells.
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Kerkhofs M, Vervloessem T, Bittremieux M, and Bultynck G
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- Cell Death drug effects, Humans, Lymphoma, B-Cell genetics, Lymphoma, B-Cell metabolism, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, B-Cell drug therapy, Lymphoma, B-Cell pathology, Peptides pharmacology
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- 2019
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155. Pathophysiological consequences of isoform-specific IP 3 receptor mutations.
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Kerkhofs M, Seitaj B, Ivanova H, Monaco G, Bultynck G, and Parys JB
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- Animals, Calcium metabolism, Calcium Signaling, Gene Expression Regulation, Humans, Inositol 1,4,5-Trisphosphate Receptors chemistry, Protein Isoforms, Disease Susceptibility, Inositol 1,4,5-Trisphosphate Receptors genetics, Inositol 1,4,5-Trisphosphate Receptors metabolism, Mutation
- Abstract
Ca
2+ signaling governs a diverse range of cellular processes and, as such, is subject to tight regulation. A main component of the complex intracellular Ca2+ -signaling network is the inositol 1,4,5-trisphosphate (IP3 ) receptor (IP3 R), a tetrameric channel that mediates Ca2+ release from the endoplasmic reticulum (ER) in response to IP3 . IP3 R function is controlled by a myriad of factors, such as Ca2+ , ATP, kinases and phosphatases and a plethora of accessory and regulatory proteins. Further complexity in IP3 R-mediated Ca2+ signaling is the result of the existence of three main isoforms (IP3 R1, IP3 R2 and IP3 R3) that display distinct functional characteristics and properties. Despite their abundant and overlapping expression profiles, IP3 R1 is highly expressed in neurons, IP3 R2 in cardiomyocytes and hepatocytes and IP3 R3 in rapidly proliferating cells as e.g. epithelial cells. As a consequence, dysfunction and/or dysregulation of IP3 R isoforms will have distinct pathophysiological outcomes, ranging from neurological disorders for IP3 R1 to dysfunctional exocrine tissues and autoimmune diseases for IP3 R2 and -3. Over the past years, several IP3 R mutations have surfaced in the sequence analysis of patient-derived samples. Here, we aimed to provide an integrative overview of the clinically most relevant mutations for each IP3 R isoform and the subsequent molecular mechanisms underlying the etiology of the disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2018
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156. Role of Mitochondria-Associated ER Membranes in Calcium Regulation in Cancer-Specific Settings.
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Morciano G, Marchi S, Morganti C, Sbano L, Bittremieux M, Kerkhofs M, Corricelli M, Danese A, Karkucinska-Wieckowska A, Wieckowski MR, Bultynck G, Giorgi C, and Pinton P
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- Animals, Humans, Membrane Microdomains metabolism, Membrane Proteins metabolism, Mitochondrial Proteins metabolism, Calcium metabolism, Endoplasmic Reticulum metabolism, Mitochondria metabolism, Neoplasms metabolism
- Abstract
Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are highly specialized subcellular compartments that are shaped by ER subdomains juxtaposed to mitochondria but are biochemically distinct from pure ER and pure mitochondria. MAMs are enriched in enzymes involved in lipid synthesis and transport, channels for calcium transfer, and proteins with oncogenic/oncosuppressive functions that modulate cell signaling pathways involved in physiological and pathophysiological processes. The term "cancer" denotes a group of disorders that result from uncontrolled cell growth driven by a mixture of genetic and environmental components. Alterations in MAMs are thought to account for the onset as well as the progression and metastasis of cancer and have been a focus of investigation in recent years. In this review, we present the current state of the art regarding MAM-resident proteins and their relevance, alterations, and deregulating functions in different types of cancer from a cell biology and clinical perspective., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2018
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157. Bcl-2 inhibitors as anti-cancer therapeutics: The impact of and on calcium signaling.
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Vervloessem T, Kerkhofs M, La Rovere RM, Sneyers F, Parys JB, and Bultynck G
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- Animals, Apoptosis drug effects, Humans, Models, Biological, Proto-Oncogene Proteins c-bcl-2 metabolism, Antineoplastic Agents pharmacology, Calcium Signaling drug effects, Proto-Oncogene Proteins c-bcl-2 antagonists & inhibitors
- Abstract
Bcl-2-protein family members are essential regulators of apoptosis. Anti-apoptotic Bcl-2 proteins ensure cell survival via different mechanisms, including via binding of pro-apoptotic Bcl-2-family members and the modulation of intracellular Ca
2+ -transport systems. Many cancer cells upregulate these proteins to overcome the consequences of ongoing oncogenic stress. Bcl-2 inhibition leading to cell death, therefore emerged as a novel cancer therapy. Different Bcl-2 inhibitors have already been developed including the hydrophobic cleft-targeting BH3 mimetics, which antagonize Bcl-2's ability to scaffold and neutralize pro-apoptotic Bcl-2-family members. As such, the BH3 mimetics have progressed into clinical studies as precision medicines. Furthermore, new inhibitors that target Bcl-2's BH4 domain have been developed as promising anti-cancer tools. Given Bcl-2's role in Ca2+ signaling, these drugs and tools can impact Ca2+ signaling. In addition to this, some Bcl-2 inhibitors may have "off-target" effects that cause Ca2+ -signaling dysregulation not only in cancer cells but also in healthy cells, resulting in adverse effects. In this review, we aim to provide an up-to-date overview of the involvement of intracellular Ca2+ signaling in the working mechanism and "off-target" effects of the different Bcl-2-antagonizing small molecules and peptides., (Copyright © 2017 Elsevier Ltd. All rights reserved.)- Published
- 2018
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158. Emerging molecular mechanisms in chemotherapy: Ca 2+ signaling at the mitochondria-associated endoplasmic reticulum membranes.
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Kerkhofs M, Bittremieux M, Morciano G, Giorgi C, Pinton P, Parys JB, and Bultynck G
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- Animals, Antineoplastic Agents therapeutic use, Calcium metabolism, Endoplasmic Reticulum genetics, Humans, Mitochondria genetics, Neoplasms genetics, Neoplasms metabolism, Antineoplastic Agents metabolism, Calcium Signaling, Endoplasmic Reticulum metabolism, Mitochondria metabolism, Mitochondrial Membranes metabolism, Neoplasms drug therapy
- Abstract
Inter-organellar communication often takes the form of Ca
2+ signals. These Ca2+ signals originate from the endoplasmic reticulum (ER) and regulate different cellular processes like metabolism, fertilization, migration, and cell fate. A prime target for Ca2+ signals are the mitochondria. ER-mitochondrial Ca2+ transfer is possible through the existence of mitochondria-associated ER membranes (MAMs), ER structures that are in the proximity of the mitochondria. This creates a micro-domain in which the Ca2+ concentrations are manifold higher than in the cytosol, allowing for rapid mitochondrial Ca2+ uptake. In the mitochondria, the Ca2+ signal is decoded differentially depending on its spatiotemporal characteristics. While Ca2+ oscillations stimulate metabolism and constitute pro-survival signaling, mitochondrial Ca2+ overload results in apoptosis. Many chemotherapeutics depend on efficient ER-mitochondrial Ca2+ signaling to exert their function. However, several oncogenes and tumor suppressors present in the MAMs can alter Ca2+ signaling in cancer cells, rendering chemotherapeutics ineffective. In this review, we will discuss recent studies that connect ER-mitochondrial Ca2+ transfer, tumor suppressors and oncogenes at the MAMs, and chemotherapy.- Published
- 2018
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159. Endoplasmic Reticulum-Mitochondrial Ca 2+ Fluxes Underlying Cancer Cell Survival.
- Author
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Ivanova H, Kerkhofs M, La Rovere RM, and Bultynck G
- Abstract
Calcium ions (Ca
2+ ) are crucial, ubiquitous, intracellular second messengers required for functional mitochondrial metabolism during uncontrolled proliferation of cancer cells. The mitochondria and the endoplasmic reticulum (ER) are connected via "mitochondria-associated ER membranes" (MAMs) where ER-mitochondria Ca2+ transfer occurs, impacting the mitochondrial biology related to several aspects of cellular survival, autophagy, metabolism, cell death sensitivity, and metastasis, all cancer hallmarks. Cancer cells appear addicted to these constitutive ER-mitochondrial Ca2+ fluxes for their survival, since they drive the tricarboxylic acid cycle and the production of mitochondrial substrates needed for nucleoside synthesis and proper cell cycle progression. In addition to this, the mitochondrial Ca2+ uniporter and mitochondrial Ca2+ have been linked to hypoxia-inducible factor 1α signaling, enabling metastasis and invasion processes, but they can also contribute to cellular senescence induced by oncogenes and replication. Finally, proper ER-mitochondrial Ca2+ transfer seems to be a key event in the cell death response of cancer cells exposed to chemotherapeutics. In this review, we discuss the emerging role of ER-mitochondrial Ca2+ fluxes underlying these cancer-related features.- Published
- 2017
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160. Alterations in Ca 2+ Signalling via ER-Mitochondria Contact Site Remodelling in Cancer.
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Kerkhofs M, Giorgi C, Marchi S, Seitaj B, Parys JB, Pinton P, Bultynck G, and Bittremieux M
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- Animals, Endoplasmic Reticulum pathology, Humans, Intracellular Membranes pathology, Membrane Microdomains pathology, Membrane Proteins metabolism, Mitochondria pathology, Mitochondrial Proteins metabolism, Neoplasms pathology, Tumor Microenvironment, Calcium Signaling, Endoplasmic Reticulum metabolism, Intracellular Membranes metabolism, Membrane Microdomains metabolism, Mitochondria metabolism, Neoplasms metabolism
- Abstract
Inter-organellar contact sites establish microdomains for localised Ca
2+ -signalling events. One of these microdomains is established between the ER and the mitochondria. Importantly, the so-called mitochondria-associated ER membranes (MAMs) contain, besides structural proteins and proteins involved in lipid exchange, several Ca2+ -transport systems, mediating efficient Ca2+ transfer from the ER to the mitochondria. These Ca2+ signals critically control several mitochondrial functions, thereby impacting cell metabolism, cell death and survival, proliferation and migration. Hence, the MAMs have emerged as critical signalling hubs in physiology, while their dysregulation is an important factor that drives or at least contributes to oncogenesis and tumour progression. In this book chapter, we will provide an overview of the role of the MAMs in cell function and how alterations in the MAM composition contribute to oncogenic features and behaviours.- Published
- 2017
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161. Endoplasmic Reticulum-Mitochondria Communication Through Ca 2+ Signaling: The Importance of Mitochondria-Associated Membranes (MAMs).
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Marchi S, Bittremieux M, Missiroli S, Morganti C, Patergnani S, Sbano L, Rimessi A, Kerkhofs M, Parys JB, Bultynck G, Giorgi C, and Pinton P
- Subjects
- Animals, Apoptosis, Endoplasmic Reticulum pathology, Energy Metabolism, Humans, Membrane Microdomains pathology, Mitochondria pathology, Mitochondrial Membrane Transport Proteins metabolism, Mitochondrial Membranes pathology, Calcium Signaling, Endoplasmic Reticulum metabolism, Membrane Microdomains metabolism, Membrane Proteins metabolism, Mitochondria metabolism, Mitochondrial Membranes metabolism, Mitochondrial Proteins metabolism
- Abstract
The execution of proper Ca
2+ signaling requires close apposition between the endoplasmic reticulum (ER) and mitochondria. Hence, Ca2+ released from the ER is "quasi-synaptically" transferred to mitochondrial matrix, where Ca2+ stimulates mitochondrial ATP synthesis by activating the tricarboxylic acid (TCA) cycle. However, when the Ca2+ transfer is excessive and sustained, mitochondrial Ca2+ overload induces apoptosis by opening the mitochondrial permeability transition pore. A large number of regulatory proteins reside at mitochondria-associated ER membranes (MAMs) to maintain the optimal distance between the organelles and to coordinate the functionality of both ER and mitochondrial Ca2+ transporters or channels. In this chapter, we discuss the different pathways involved in the regulation of ER-mitochondria Ca2+ flux and describe the activities of the various Ca2+ players based on their primary intra-organelle localization.- Published
- 2017
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162. The direction of shift-work rotation impacts metabolic risk independent of chronotype and social jetlag--an exploratory pilot study.
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Kantermann T, Duboutay F, Haubruge D, Hampton S, Darling AL, Berry JL, Kerkhofs M, Boudjeltia KZ, and Skene DJ
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- Adult, Belgium, Biomarkers blood, Cardiovascular Diseases etiology, Circadian Rhythm, Humans, Male, Metabolome, Middle Aged, Occupational Health, Pilot Projects, Risk Factors, Social Behavior, Metabolic Diseases etiology, Work Schedule Tolerance physiology, Work Schedule Tolerance psychology
- Abstract
The aim of this pilot study was to explore the risk of metabolic abnormalities in steel workers employed in different shift-work rotations. Male workers in a steel factory [16 employed in a fast clockwise rotation (CW), 18 in slow counterclockwise rotation (CC), 9 day workers (DW); mean age 43.3 ± SD 6.8 years] with at least 5 years experience in their current work schedule participated. All workers provided fasting blood samples between 06:00 and 08:00 h for plasma glucose, insulin, apo-lipoproteins A and B (ApoA, ApoB), high- and low-density lipoproteins (HDL and LDL), total cholesterol (tCH), triglycerides (TG), minimally oxidized (mox) LDL, C-reactive protein (CRP), interleukin-8 (IL-8) and serum 25-hydroxyvitamin D (25(OH)D). HOMA index (homeostatic model assessment) was calculated to evaluate insulin resistance, beta cell function and risk of diabetes. Information on demographics, health, stimulants, sleep, social and work life, chronotype (phase of entrainment) and social jetlag (difference between mid-sleep on workdays and free days) as a surrogate for circadian disruption was collected by questionnaire. Neither chronotype nor social jetlag was associated with any of the metabolic risk blood markers. There were no significant differences in 25(OH)D, ApoA, ApoB, CRP, HDL, IL-8, insulin, LDL, mox-LDL, mox-LDL/ApoB ratio, tCH and TG levels between the three work groups. Although we did observe absolute differences in some of these markers, the small sample size of our study population might prevent these differences being statistically significant. Fasting glucose and HOMA index were significantly lower in CW compared to DW and CC, indicating lower metabolic risk. Reasons for the lower fasting glucose and HOMA index in CW workers remains to be clarified. Future studies of workers in different shift rotations are warranted to understand better the differential effects of shift-work on individual workers and their health indices.
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- 2014
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163. Effects of a 3-week dehydroepiandrosterone administration on sleep, sex steroids and multiple 24-h hormonal profiles in postmenopausal women: a pilot study.
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Caufriez A, Leproult R, L'Hermite-Balériaux M, Kerkhofs M, and Copinschi G
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- Androgens blood, Cross-Over Studies, Double-Blind Method, Drug Administration Schedule, Estradiol blood, Female, Humans, Middle Aged, Postmenopause drug effects, Testosterone blood, Dehydroepiandrosterone administration & dosage, Dehydroepiandrosterone therapeutic use, Gonadal Steroid Hormones blood
- Abstract
Objective: Dehydroepiandrosterone (DHEA) administration is widely evocated as a 'fountain of youth', but previous studies have provided inconsistent results. We aimed to investigate in healthy postmenopausal women the effects of a 3-week oral DHEA administration on individual steroid levels, multiple 24-h hormonal profiles and sleep architecture., Design: Seven healthy nonobese postmenopausal women, off hormone replacement therapy for ≥2 months, were investigated in a randomized, crossover, double-blind, placebo-controlled study. For 3 weeks, subjects took daily at 2300 h a capsule of either 50 mg DHEA or placebo. Sleep was polygraphically recorded during the last two nights, and blood samples were drawn at 15-min intervals during the last 24 h., Results: Under DHEA, testosterone and estradiol levels were increased in all individuals. Individual increments were highly variable, not related to each other, and were not related to placebo values. However, the testosterone to estradiol ratio was markedly increased under DHEA. DHEA administration had little, if any, effect on thyroid function, GH secretion, prolactin, ACTH and cortisol profiles. DHEA effects on sleep appeared to be mediated by its conversion to androgens and oestrogens: sleep quality was enhanced by increments in testosterone and dampened by increments in estradiol levels., Conclusion: As DHEA-induced elevations in testosterone and estradiol levels varied widely between individuals and were largely unpredictable, DHEA administration might not be the most appropriate approach to compensate for the reduction observed in androgen and oestrogen production in postmenopausal women. DHEA supplementation may result either in sleep stimulation or in inhibition, depending on the ratio between DHEA-induced increments in testosterone vs estradiol., (© 2013 John Wiley & Sons Ltd.)
- Published
- 2013
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164. A new device to mimic intermittent hypoxia in mice.
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Chodzyński KJ, Conotte S, Vanhamme L, Van Antwerpen P, Kerkhofs M, Legros JL, Vanhaeverbeek M, Van Meerhaeghe A, Coussement G, Boudjeltia KZ, and Legrand A
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- Air Conditioning methods, Animals, Hemoglobins metabolism, Mice, Oximetry, Oxygen Consumption, Pulmonary Disease, Chronic Obstructive physiopathology, Sleep Apnea, Obstructive physiopathology, Air Conditioning instrumentation, Hypoxia physiopathology
- Abstract
Intermittent hypoxia (hypoxia-reoxygenation) is often associated with cardiovascular morbidity and mortality. We describe a new device which can be used to submit cohorts of mice to controlled and standardised hypoxia-normoxia cycles at an individual level. Mice were placed in individual compartments to which similar gas flow parameters were provided using an open loop strategy. Evaluations made using computational fluid dynamics were confirmed by studying changes in haemoglobin oxygen saturation in vivo. We also modified the parameters of the system and demonstrated its ability to generate different severities of cyclic hypoxemia very precisely, even with very high frequency cycles of hypoxia-reoxygenation. The importance of the parameters on reoxygenation was shown. This device will allow investigators to assess the effects of hypoxia-reoxygenation on different pathological conditions, such as obstructive sleep apnoea or chronic obstructive pulmonary disease.
- Published
- 2013
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165. Atherosclerotic risk and social jetlag in rotating shift-workers: first evidence from a pilot study.
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Kantermann T, Duboutay F, Haubruge D, Kerkhofs M, Schmidt-Trucksäss A, and Skene DJ
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- Adult, Blood Pressure, Heart Rate, Humans, Male, Middle Aged, Occupational Diseases physiopathology, Pilot Projects, Pulse Wave Analysis, Risk Factors, Work Schedule Tolerance psychology, Atherosclerosis etiology, Chronobiology Disorders physiopathology, Occupational Diseases etiology, Work Schedule Tolerance physiology
- Abstract
Objective: The aim of this study was to identify atherosclerotic risk using pulse wave velocity (PWV) in steel workers employed in different shift-work rotations, and to elucidate its relationship to social jetlag and shift schedule details., Participants: Male workers in a steel factory (n=77, 32 fast clockwise (CW), 30 slow counterclockwise (CC), 15 day workers (DW); mean age 42 ± SD 7.6 yrs) with at least 5 years of experience in their current work schedule participated., Methods: All workers completed questionnaires on demographics, health, psychotropic agents, sleep, social and work life, social jetlag (difference between mid-sleep time on workdays and days off used as a marker of circadian disruption) and chronotype (mid-sleep time on free days corrected for sleep deficit on workdays). In 63 workers we measured PWV, blood pressure (BP), heart rate (HR) between 08:00 and 12:30 h in controlled posture conditions (no caffeine/smoking/exercise)., Results: There was no significant difference in PWV (covariates: age, BP) between the different shift-rotations (CW, CC and DW). In all workers combined, HR and social jetlag were significantly positively correlated. Demographic variables did not differ between shift-workers and day workers; shift-workers (CW, CC) reported significantly more stomach upsets, digestion problems, weight fluctuations, and social jetlag. The CW and CC workers did not differ in ratings of how shift-work affected sleep, social and work life., Conclusions: PWV was not different between the two shift-rotations. This pilot study shows first evidence that HR is related to social jetlag, and therefore warrants more studies in different shift schedules.
- Published
- 2013
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166. From total sleep deprivation to cardiovascular disease: a key role for the immune system?
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Kerkhofs M and Boudjeltia KZ
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- Humans, Male, Circadian Rhythm physiology, Leukocyte Count, Sleep Deprivation blood
- Published
- 2012
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167. Mood, alertness, and performance in response to sleep deprivation and recovery sleep in experienced shiftworkers versus non-shiftworkers.
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Wehrens SM, Hampton SM, Kerkhofs M, and Skene DJ
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- Adult, Attention physiology, Humans, Male, Middle Aged, Reaction Time, Regression Analysis, Task Performance and Analysis, Wakefulness physiology, Work Schedule Tolerance physiology, Affect physiology, Circadian Rhythm physiology, Psychomotor Performance physiology, Sleep physiology, Sleep Deprivation physiopathology
- Abstract
Previous studies have shown increased sleepiness and mood changes in shiftworkers, which may be due to sleep deprivation or circadian disruption. Few studies, however, have compared responses of experienced shiftworkers and non-shiftworkers to sleep deprivation in an identical laboratory setting. The aim of this laboratory study, therefore, was to compare long-term shiftworkers and non-shiftworkers and to investigate the effects of one night of total sleep deprivation (30.5 h of continuous wakefulness) and recovery sleep on psychomotor vigilance, self-rated alertness, and mood. Eleven experienced male shiftworkers (shiftwork ≥5 yrs) were matched with 14 non-shiftworkers for age (mean ± SD: 35.7 ± 7.2 and 32.5 ± 6.2 yrs, respectively) and body mass index (BMI) (28.7 ± 3.8 and 26.6 ± 3.4 kg/m(2), respectively). After keeping a 7-d self-selected sleep/wake cycle (7.5/8 h nocturnal sleep), both groups entered a laboratory session consisting of a night of adaptation sleep and a baseline sleep (each 7.5/8 h), a sleep deprivation night, and recovery sleep (4-h nap plus 7.5/8 h nighttime sleep). Subjective alertness and mood were assessed with the Karolinska Sleepiness Scale (KSS) and 9-digit rating scales, and vigilance was measured by the visual psychomotor vigilance test (PVT). A mixed-model regression analysis was carried out on data collected every hour during the sleep deprivation night and on all days (except for the adaptation day), at .25, 4.25, 5.25, 11.5, 12.5, and 13.5 h after habitual wake-up time. Despite similar circadian phase (melatonin onset), demographics, food intake, body posture, and environmental light, shiftworkers felt significantly more alert, more cheerful, more elated, and calmer than non-shiftworkers throughout the laboratory study. In addition, shiftworkers showed a faster median reaction time (RT) compared to non-shiftworkers, although four other PVT parameters did not differ between the groups. As expected, both groups showed a decrease in subjective alertness and PVT performance during and following the sleep deprivation night. Subjective sleepiness and most aspects of PVT performance returned to baseline levels after a nap and recovery sleep. The mechanisms underlying the observed differences between shiftworkers and non-shiftworkers require further study, but may be related to the absence of shiftwork the week prior to and during the laboratory study as well as selection into and out of shiftwork.
- Published
- 2012
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168. Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery.
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Faraut B, Boudjeltia KZ, Vanhamme L, and Kerkhofs M
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- Adult, Female, Humans, Male, Neurosecretory Systems physiopathology, Sex Factors, Sleep physiology, Sleep Deprivation immunology, Sleep Deprivation physiopathology, Cardiovascular Diseases etiology, Immunity physiology, Inflammation etiology, Sleep Deprivation complications
- Abstract
In addition to its effects on cognitive function, compelling evidence links sleep loss to alterations in the neuroendocrine, immune and inflammatory systems with potential negative public-health ramifications. The evidence to suggest that shorter sleep is associated with detrimental health outcomes comes from both epidemiological and experimental sleep deprivation studies. This review will focus on the post-sleep deprivation and recovery changes in immune and inflammatory functions in well-controlled sleep restriction laboratory studies. The data obtained indicate non-specific activation of leukocyte populations and a state of low-level systemic inflammation after sleep loss. Furthermore, one night of recovery sleep does not allow full recovery of a number of these systemic immune and inflammatory markers. We will speculate on the mechanism(s) that link(s) sleep loss to these responses and to the progression of cardiovascular disease. The immune and inflammatory responses to chronic sleep restriction suggest that chronic exposure to reduced sleep (<6 h/day) and insufficient time for recovery sleep could have gradual deleterious effects, over years, on cardiovascular pathogenesis with a heightened risk in women and in night and shift workers. Finally, we will examine countermeasures, e.g., napping or sleep extension, which could improve the recovery processes, in terms of alertness and immune and inflammatory parameters, after sleep restriction., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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169. Progesterone prevents sleep disturbances and modulates GH, TSH, and melatonin secretion in postmenopausal women.
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Caufriez A, Leproult R, L'Hermite-Balériaux M, Kerkhofs M, and Copinschi G
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- Adrenocorticotropic Hormone blood, Aged, Double-Blind Method, Estrogen Replacement Therapy methods, Female, Gonadal Steroid Hormones analysis, Gonadal Steroid Hormones blood, Human Growth Hormone blood, Humans, Hydrocortisone blood, Melatonin blood, Middle Aged, Placebos, Postmenopause blood, Postmenopause metabolism, Progesterone pharmacology, Thyrotropin blood, Thyroxine blood, Human Growth Hormone metabolism, Melatonin metabolism, Postmenopause drug effects, Progesterone therapeutic use, Sleep Wake Disorders prevention & control, Thyrotropin metabolism
- Abstract
Context: A number of neuroactive progesterone metabolites produce sedative-like effects. However, the effects of progesterone administration on sleep are not well characterized., Objective: To investigate the effects of a 3-wk progesterone administration on sleep architecture and multiple hormonal profiles., Subjects: Eight healthy postmenopausal women, 48-74 yr old, without sleep complaints or vasomotor symptoms. None was on hormone replacement therapy. They did not take any medication for ≥ 2 months., Design: Randomized, double-blind, placebo-controlled study. For 3 wk, subjects took daily at 2300 h a capsule of either 300 mg of progesterone or placebo. Sleep was polygraphically recorded during the last two nights, and blood samples were obtained at 15-min intervals for 24 h., Results: During the first night (no blood sampling), sleep was similar in both conditions. Under placebo, blood sampling procedure was associated with marked sleep disturbances, which were considerably reduced under progesterone treatment: mean duration of wake after sleep onset was 53% lower, slow-wave sleep duration almost 50% higher, and total slow-wave activity (reflecting duration and intensity of deep sleep) almost 45% higher under progesterone than under placebo (P ≤ 0.05). Nocturnal GH secretion was increased, and evening and nocturnal TSH levels were decreased under progesterone (P ≤ 0.05)., Conclusions: Progesterone had no effect on undisturbed sleep but restored normal sleep when sleep was disturbed (while currently available hypnotics tend to inhibit deep sleep), acting as a "physiologic" regulator rather than as a hypnotic drug. Use of progesterone might provide novel therapeutic strategies for the treatment of sleep disturbances, in particular in aging where sleep is fragmented and of lower quality.
- Published
- 2011
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170. Benefits of napping and an extended duration of recovery sleep on alertness and immune cells after acute sleep restriction.
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Faraut B, Boudjeltia KZ, Dyzma M, Rousseau A, David E, Stenuit P, Franck T, Van Antwerpen P, Vanhaeverbeek M, and Kerkhofs M
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- Adult, Atherosclerosis immunology, Data Interpretation, Statistical, Female, Humans, Hydrocortisone metabolism, Inflammation immunology, Leukocyte Count, Male, Neutrophils physiology, Peroxidase metabolism, Polysomnography, Saliva metabolism, Software, Young Adult, Attention physiology, Immunity, Cellular physiology, Sleep immunology, Sleep Deprivation immunology
- Abstract
Understanding the interactions between sleep and the immune system may offer insight into why short sleep duration has been linked to negative health outcomes. We, therefore, investigated the effects of napping and extended recovery sleep after sleep restriction on the immune and inflammatory systems and sleepiness. After a baseline night, healthy young men slept for a 2-h night followed by either a standard 8-h recovery night (n=12), a 30-min nap (at 1 p.m.) in addition to an 8-h recovery night (n=10), or a 10-h extended recovery night (n=9). A control group slept 3 consecutive 8-h nights (n=9). Subjects underwent continuous electroencephalogram polysomnography and blood was sampled every day at 7 a.m. Leukocytes, inflammatory and atherogenesis biomarkers (high-sensitivity C-reactive protein, interleukin-8, myeloperoxidase, fibrinogen and apolipoproteins ApoB/ApoA), sleep patterns and sleepiness were investigated. All parameters remained unchanged in the control group. After sleep restriction, leukocyte and - among leukocyte subsets - neutrophil counts were increased, an effect that persisted after the 8-h recovery sleep, but, in subjects who had a nap or a 10-h recovery sleep, these values returned nearly to baseline. Inflammatory and atherogenesis biomarkers were unchanged except for higher myeloperoxidase levels after sleep restriction. The increased sleepiness after sleep restriction was reversed better in the nap and extended sleep recovery conditions. Saliva cortisol decreased immediately after the nap. Our results indicate that additional recovery sleep after sleep restriction provided by a midday nap prior to recovery sleep or a sleep extended night can improve alertness and return leukocyte counts to baseline values., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2011
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171. Temporal dissociation between myeloperoxidase (MPO)-modified LDL and MPO elevations during chronic sleep restriction and recovery in healthy young men.
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Boudjeltia KZ, Faraut B, Esposito MJ, Stenuit P, Dyzma M, Antwerpen PV, Brohée D, Vanhamme L, Moguilevsky N, Vanhaeverbeek M, and Kerkhofs M
- Subjects
- Adult, C-Reactive Protein metabolism, Fibrinogen metabolism, Humans, Inflammation Mediators blood, Insulin-Like Growth Factor I metabolism, Interleukin-8 blood, Leukocytes metabolism, Male, Time Factors, Young Adult, Health, Lipoproteins, LDL metabolism, Peroxidase blood, Sleep physiology, Sleep Deprivation blood, Sleep Deprivation physiopathology
- Abstract
Objectives: Many studies have evaluated the ways in which sleep disturbances may influence inflammation and the possible links of this effect to cardiovascular risk. Our objective was to investigate the effects of chronic sleep restriction and recovery on several blood cardiovascular biomarkers., Methods and Results: Nine healthy male non-smokers, aged 22-29 years, were admitted to the Sleep Laboratory for 11 days and nights under continuous electroencephalogram polysomnography. The study consisted of three baseline nights of 8 hours sleep (from 11 pm to 7 am), five sleep-restricted nights, during which sleep was allowed only between 1 am and 6 am, and three recovery nights of 8 hours sleep (11 pm to 7 am). Myeloperoxidase-modified low-density lipoprotein levels increased during the sleep-restricted period indicating an oxidative stress. A significant increase in the quantity of slow-wave sleep was measured during the first recovery night. After this first recovery night, insulin-like growth factor-1 levels increased and myeloperoxidase concentration peaked., Conclusions: We observed for the first time that sleep restriction and the recovery process are associated with differential changes in blood biomarkers of cardiovascular disease.
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- 2011
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172. Automatic sleep spindles detection--overview and development of a standard proposal assessment method.
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Devuyst S, Dutoit T, Stenuit P, and Kerkhofs M
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Reproducibility of Results, Sensitivity and Specificity, Algorithms, Brain physiopathology, Diagnosis, Computer-Assisted methods, Electroencephalography methods, Pattern Recognition, Automated methods, Polysomnography methods, Sleep, Sleep Wake Disorders diagnosis, Sleep Wake Disorders physiopathology
- Abstract
Since the 1970s, various automatic sleep spindles procedures have been implemented and presented in the literature. Unfortunately, their results are not easily comparable because the databases, the assessment methods and the terminologies employed are often radically different. In this study, we propose a systematic assessment method for any automatic sleep spindles detection algorithm. We apply this assessment method to our own automatic detection process in order to illustrate and legitimate its use. We obtain a global sensitivity of 70.20%, for a false positive proportion (relative to the total number of visually scored sleep spindles) of only 26.44% (False positive rate = 1.38% and specificity = 98.62%).
- Published
- 2011
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173. Neuropeptide Y and sleep.
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Dyzma M, Boudjeltia KZ, Faraut B, and Kerkhofs M
- Subjects
- Animals, Brain Mapping, Corticotropin-Releasing Hormone blood, Eating physiology, Electroencephalography, Energy Metabolism physiology, Homeostasis physiology, Humans, Receptors, Neuropeptide Y physiology, Sympathetic Nervous System physiology, Brain physiology, Circadian Rhythm physiology, Neuropeptide Y physiology, Sleep physiology, Wakefulness physiology
- Abstract
Neuropeptide Y (NPY), a 36-amino-acid peptide from the pancreatic polypeptide family, is one of the more abundant peptides in the central nervous system. It acts as a neurohormone and as a neuromodulator. NPY is widely distributed in the brain, particularly the hypothalamus, the amygdala, the locus coeruleus and the cerebral cortex. At least six NPY receptors subtypes have been identified. NPY is involved in the regulation of several physiological functions such as food intake, hormonal release, circadian rhythms, cardiovascular disease, thermoregulation, stress response, anxiety and sleep. Sleep promoting effects of NPY as well as wakefulness effects of NPY were found in animals, depending on the site of injection as well as on the functional state of the structure. In humans, NPY was found to have hypnotic properties, possibly acting as a physiological antagonist of corticotropin-releasing hormone (CRH). In conclusion, NPY participates in sleep regulation in humans, particularly in the timing of sleep onset and may as such play a role in the integration of sleep regulation, food intake and metabolism., (Copyright 2009 Elsevier Ltd. All rights reserved.)
- Published
- 2010
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174. Automatic K-complexes detection in sleep EEG recordings using likelihood thresholds.
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Devuyst S, Dutoit T, Stenuit P, and Kerkhofs M
- Subjects
- Differential Threshold physiology, Humans, Reproducibility of Results, Sensitivity and Specificity, Algorithms, Diagnosis, Computer-Assisted methods, Electroencephalography methods, Pattern Recognition, Automated methods, Sleep physiology
- Abstract
In this paper, we present an automatic method for K-complexes detection based on features extraction and the use of fuzzy thresholds. The validity of our process was examined on the basis of two visual K-complexes scorings performed on 5 excerpts of 30 minutes. Results were investigated through all different sleep stages. The algorithm provides global true positive rates of 61.72% and 60.94%, respectively with scorer 1 and scorer 2. The false positive proportions (compared to the total number of visually scored K-complexes) are of 19.62% and 181.25%, while the false positive rates estimated on a one 1 second resolution are only of 0.53% and 1.53%. These results suggest that our approach is completely suitable since its performances are similar to those of the human scorers.
- Published
- 2010
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175. Effects of sleep restriction on cognition in women.
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Stenuit P and Kerkhofs M
- Subjects
- Adult, Aging psychology, Attention physiology, Electroencephalography, Eye Movements physiology, Humans, Male, Memory physiology, Middle Aged, Neuropsychological Tests, Polysomnography, Psychomotor Performance physiology, Reaction Time physiology, Wechsler Scales, Cognition physiology, Sleep Deprivation psychology
- Abstract
The aim of the present study was to investigate how three nights of sleep restriction affected cognitive functions in young and aged healthy women. Ten young (20-30 years) and ten aged (55-65 years) women participated to the study. After one baseline night (11 pm-07 am), their sleep was restricted to 4h per night (01-05 am) during three nights. A recovery night of 8h (11 pm-07 am) followed the sleep restriction. The neurobehavioural assessment included evaluation of Attention (Stroop, Trail Making test, Tests of Attentional Performance), Memory (Buschke, Logical Memory, PASAT, Brown Peterson), Addition of numbers and Abstraction (Wisconsin). Sleep restriction decreased significantly the speed of execution, particularly in the young women, without affecting the accuracy of the answers. This effect was the most significant on reaction times in simple tests. The more complex tasks (PASAT, Brown Peterson, Logical Memory, Addition of numbers, Wisconsin) were not affected. However, the inhibition of an automatic activity (Stroop test) and the formation of a memory trace (Buschke memory test) were disturbed in both young and older women.
- Published
- 2008
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176. Removal of ECG artifacts from EEG using a modified independent component analysis approach.
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Devuyst S, Dutoit T, Stenuit P, Kerkhofs M, and Stanus E
- Subjects
- Adult, Aged, Artificial Intelligence, Female, Humans, Male, Middle Aged, Principal Component Analysis, Reproducibility of Results, Sensitivity and Specificity, Signal Processing, Computer-Assisted, Algorithms, Artifacts, Diagnosis, Computer-Assisted methods, Electrocardiography methods, Electroencephalography methods, Pattern Recognition, Automated methods, Sleep Wake Disorders diagnosis
- Abstract
In this paper, we introduce a new automatic method for electrocardiogram (ECG) artifact elimination from the electroencephalogram (EEG) or the electrooculogram (EOG). It is based on a modification of the independent component analysis (ICA) algorithm which gives promising results while only using a single-channel EEG (or EOG) and the ECG. To check the effectiveness of our approach, we compared its correction rate with those obtained by ensemble average subtraction (EAS) and adaptive filtering (AF). For this purpose, we applied these algorithms to 10 excerpts of polysomnographic sleep recordings containing ECG artifacts and other typical artifacts (e.g. movement, sweat, respiration, etc.). Two hundred successive interference peaks were examined in each excerpt to compute correction rates. We found that our modified ICA was the most robust to various waveforms of cardiac interference and to the presence of others artifacts, with a correction rate of 91.0%, against 83.5% for EAS and 83.1% for AF.
- Published
- 2008
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177. Sleep restriction increases blood neutrophils, total cholesterol and low density lipoprotein cholesterol in postmenopausal women: A preliminary study.
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Kerkhofs M, Boudjeltia KZ, Stenuit P, Brohée D, Cauchie P, and Vanhaeverbeek M
- Subjects
- Aged, Cardiovascular Diseases etiology, Cell Count, Estrogen Replacement Therapy, Female, Humans, Middle Aged, Pilot Projects, Risk Factors, Cholesterol blood, Cholesterol, LDL blood, Neutrophils cytology, Postmenopause blood, Sleep Deprivation blood
- Abstract
Objectives: This study examines the effects of sleep restricted to 4h for three consecutive nights on blood parameters known to be associated with cardiovascular risk in healthy postmenopausal women., Material and Methods: Ten healthy postmenopausal women aged 55-65 years treated with hormonal replacement therapy (HT) were included in the study. After one baseline night, three nights of sleep restricted to 4h were performed and were followed by one recovery night of 8h. Blood samplings were performed after the baseline night and after the third night of sleep restriction., Results: A significant increase in white blood cells (WBC), monocytes, neutrophils, total cholesterol, and low density lipoprotein cholesterol (LDL-c) was observed after the third night of sleep restriction., Conclusion: Sleep restriction to 4h of sleep for three consecutive nights affected two factors associated with cardiovascular risk in healthy postmenopausal women treated with HT.
- Published
- 2007
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178. Automatic sleep spindle detection in patients with sleep disorders.
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Devuyst S, Dutoit T, Didier JF, Meers F, Stanus E, Stenuit P, and Kerkhofs M
- Subjects
- Algorithms, Automation, Electroencephalography, Electrooculography, False Positive Reactions, Humans, Polysomnography, Sensitivity and Specificity, Sleep Stages, Wakefulness, Sleep physiology, Sleep Wake Disorders diagnosis
- Abstract
In this paper, we present a new automatic method for sleep spindle detection. It consist of a generalisation of the Schimicek's method that takes more types of artefacts into account and uses variable thresholds regarding the statistical properties of the signal. Validity of our process is examined on the basis of visual spindle scoring performed by an expert. Results obtained are compared to those obtained by Schimicek's method. For a specificity of 90%, we obtain a sensitivity of 76.9% while Schimicek's method has a sensitivity of 70.4%. Moreover an increase of the area under the ROC curve is observed and confirms that the detection process is improved.
- Published
- 2006
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179. Sleep apnoea-hypopnoea index is an independent predictor of high-sensitivity C-reactive protein elevation.
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Zouaoui Boudjeltia K, Van Meerhaeghe A, Doumit S, Guillaume M, Cauchie P, Brohée D, Vanhaeverbeek M, and Kerkhofs M
- Subjects
- Cardiovascular Diseases blood, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Multivariate Analysis, Polysomnography, Severity of Illness Index, C-Reactive Protein analysis, Sleep Apnea Syndromes blood
- Abstract
Background: Recent reports have identified the apnoea and hypopnoea index (AHI) as an additional independent risk factor for cardiovascular morbidity and mortality. However, several studies reported contradictory results about the association between the serum C-reactive protein (CRP) level and the severity of apnoea., Objective: The purpose of this work is to study this association in patients referred to the sleep laboratory for clinical suspicion of sleep apnoea and presenting a wide range of AHI., Methods: Forty-nine consecutive patients were included in the study. The SigmaStat software package (Jandle Scientific) was used. Multilinear regression analysis was tested using a stepwise backward selection of the explicative variables. The clinical characteristics (diabetes, hypertension, smoking habits, gender) were treated as dichotomous variables, while all other data (age, BMI, lipids, white blood cells) were continuous ones; high-sensitivity (hs)-CRP was the dependent variable., Results: In univariate analysis, AHI was correlated to hs-CRP: R = 0.43, p = 0.002. In multivariate analyses, we found an independent association between the AHI, adjusted for classical cardiovascular risk factors, and hs-CRP., Conclusion: In a sample of 49 patients, referred to the sleep laboratory for suspicion of sleep apnoea in routine practice, we observed an independent association between the AHI and hs-CRP.
- Published
- 2006
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180. Flow limitation and dynamic hyperinflation.
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Van Meerhaeghe A, Delpire P, Stenuit P, and Kerkhofs M
- Subjects
- Humans, Lung Volume Measurements, Maximal Expiratory Flow Rate, Sleep Apnea, Obstructive physiopathology
- Published
- 2005
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181. Women's sleep in health and disease.
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Dzaja A, Arber S, Hislop J, Kerkhofs M, Kopp C, Pollmächer T, Polo-Kantola P, Skene DJ, Stenuit P, Tobler I, and Porkka-Heiskanen T
- Subjects
- Adult, Aged, Animals, Disease Models, Animal, Estrogens pharmacology, Female, Humans, Middle Aged, Social Behavior, Women's Health, Circadian Rhythm, Menopause physiology, Menstruation physiology, Pregnancy physiology, Sleep physiology, Sleep Wake Disorders etiology
- Abstract
A huge amount of knowledge about sleep has accumulated during the last 5 decades following the discovery of rapid eye movement (REM) sleep. Nevertheless, there are numerous areas of considerable ignorance. One of these concerns the particularities of sleep in women. Most basic and clinical studies have been performed in male subjects, and only very recently research groups around the world have addressed women's sleep in health and disease. In this review, we summarize the present knowledge on the influence of oestrogens on the brain and on the distinctive changes of sleep across the menstrual cycle, during pregnancy and menopause. In addition, studies in female rodents are reviewed as well as the knowledge on female peculiarities regarding the interactions between sleep regulation and age-related changes in circadian rhythms. We also address specific aspects of sleep loss and sleep disorders in women. Finally, very recent studies on the sociology of sleep are summarized and future directions in the field are discussed.
- Published
- 2005
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182. [Frederic Bremer (1892-1982): a pioneer in sleep research].
- Author
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Kerkhofs M
- Subjects
- Animals, Belgium, Brain physiology, Cats, History, 20th Century, Humans, Neurophysiology history, Sleep physiology
- Published
- 2003
183. The SleepStrip: an apnoea screener for the early detection of sleep apnoea syndrome.
- Author
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Shochat T, Hadas N, Kerkhofs M, Herchuelz A, Penzel T, Peter JH, and Lavie P
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Equipment and Supplies, Humans, Middle Aged, Sensitivity and Specificity, Sleep Apnea Syndromes diagnosis
- Abstract
Sleep apnoea svndrome (SAS) is a largely undiagnosed and prevalent disorder. It is associated with cardiovascular morbidity as well as excessive daytime sleepiness and poor quality of life. In the present study the SleepStrip, a novel screening device is introduced, which is low cost and easy to use and is aimed for widespread use. The results of three independent validation studies, which compared the SleepStrip score (Sscore) against "gold standard" polysomnographically-determined apnoea/ hypopnoea index (AHI), are reported both separately and combined. Four hundred and two patients suspected of SAS underwent full polysomnography recordings concomitantly with the use of the SleepStrip. For all samples combined, the correlation between AHI and Sscore was r=0.73, sensitivity and specificity values ranged from 80-86% and 57-86% respectively, and the area under the curve derived from receiver-operating characteristic curves ranged from 0.81-0.92 at varying AHI thresholds. Though not intended as a substitute for polysomnography, the SleepStrip may provide initial screening information, which may be useful in both clinical and experimental settings.
- Published
- 2002
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184. Frédéric Bremer 1892-1982: a pioneer in sleep research.
- Author
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Kerkhofs M and Lavie P
- Abstract
Frédéric Bremer was one of the pioneer neurophysiologists who dedicated their career to understanding the neural mechanisms involved in the control of sleep-wake regulation. This paper follows his career and his major achievements. We found that Bremer's interest in sleep resulted from his unexpected observations after transecting the brain at the midcollicular level in the "encéphale isolé" preparation. The sleep-like behaviour of the animal, accompanied by slow waves in the cortex, convinced him that sleep resulted from cortical deafferentation. He was further convinced that deafferentation was the cause of sleep when he found that transecting the brain at the medullary level did not much affect the sleep-wake cycle. As we show, Bremer's views that sleep is a passive phenomenon imposed on the brain because of deafferentation was shared by most of his contemporaries. Years later Bremer admitted that he interpreted his experimental findings wrongly. He continued to investigate sleep using his preparations and made important contributions to understanding the relationships between the brainstem reticular formation and the basal forebrain hypnogenic centres, as well as the importance of light on these relationships.
- Published
- 2000
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185. Genetic control of 24-hour growth hormone secretion in man: a twin study.
- Author
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Mendlewicz J, Linkowski P, Kerkhofs M, Leproult R, Copinschi G, and Van Cauter E
- Subjects
- Adolescent, Adult, Anthropometry, Humans, Male, Sleep physiology, Twins, Dizygotic, Twins, Monozygotic, Circadian Rhythm physiology, Genetic Variation physiology, Human Growth Hormone metabolism
- Abstract
The aim of this study was to delineate the contributions of genetic and environmental factors in the regulation of the 24-h GH secretion. The 24-h profile of plasma GH was obtained at 15-min intervals in 10 pairs of monozygotic and 9 pairs of dizygotic normal male twins, aged 16-34 yr. Sleep was polygraphically monitored. Significant pulses of GH secretion were identified using a modification of the computer algorithm ULTRA. For each significant pulse, the amount of GH secreted was calculated by deconvolution. A procedure specially developed for twin studies was used to partition the variance of investigated parameters into genetic and environmental contributions. A major genetic effect was evidenced on GH secretion during wakefulness (with a heritability estimate of 0.74) and, to a lesser extent, on the 24-h GH secretion. Significant genetic influences were also identified for slow wave sleep and height. These data demonstrate that human GH secretion in young adulthood is markedly dependent on genetic factors.
- Published
- 1999
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186. Genetic and environmental influences on prolactin secretion during wake and during sleep.
- Author
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Linkowski P, Spiegel K, Kerkhofs M, L'Hermite-Balériaux M, Van Onderbergen A, Leproult R, Mendlewicz J, and Van Cauter E
- Subjects
- Adult, Circadian Rhythm physiology, Humans, Male, Osmolar Concentration, Prolactin blood, Environment, Prolactin metabolism, Sleep physiology, Twins, Dizygotic genetics, Twins, Monozygotic genetics, Wakefulness physiology
- Abstract
To delineate the contributions of genetic and environmental factors in the regulation of human prolactin (PRL) secretion, the 24-h profile of plasma PRL was obtained at 15-min intervals in 10 pairs of monozygotic and 10 pairs of dizygotic twins. Sleep was monitored polygraphically. PRL secretory rates were derived from plasma concentrations by deconvolution. Diurnal (24-h) variations were quantified by a regression curve to define nadir, acrophase, and amplitude. Pulses of PRL secretion were identified using a computerized algorithm. A procedure specifically developed for twin studies was used to partition the variance into genetic and environmental contributions. Significant genetic effects were identified for daytime PRL concentrations, rhythm amplitude, and overall wave-shape of the daily PRL profile. In contrast, environmental effects were dominant for mean concentrations during sleep, total secretory output during sleep, overall 24-h concentrations, and total 24-h secretion. However, when interindividual variations in sleep fragmentation were taken into account, the estimates of genetic variance for PRL concentrations and secretion during sleep approached statistical significance. Significant genetic influences were identified for slow-wave sleep (SWS). Because SWS is associated with increased nocturnal PRL secretion, it is possible that genetic effects on PRL secretion during sleep reflect genetic influences on SWS. In conclusion, genetic factors determine partially both the basal daytime concentrations of PRL and the temporal organization of PRL secretion over the 24-h cycle in normal young men.
- Published
- 1998
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187. Evidence against a role for the growth hormone-releasing peptide axis in human slow-wave sleep regulation.
- Author
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Moreno-Reyes R, Kerkhofs M, L'Hermite-Balériaux M, Thorner MO, Van Cauter E, and Copinschi G
- Subjects
- Adult, Dose-Response Relationship, Drug, Drug Administration Schedule, Human Growth Hormone blood, Humans, Injections, Intravenous, Male, Oligopeptides administration & dosage, Sleep Stages drug effects, Oligopeptides pharmacology, Sleep drug effects
- Abstract
A complex interrelationship exists between sleep and somatotropic activity. In humans, intravenous injections of growth hormone-releasing hormone (GHRH) given during sleep consistently stimulate slow-wave (SW) sleep, particularly when given in the latter part of the night. In the present study, the possible somnogenic effects induced under similar conditions by GH-releasing peptide (GHRP) were investigated in seven young healthy men. Bolus intravenous injections of GHRP-2 (1 microgram/kg body wt) or saline, in randomized order, were given after 60 s of the third rapid-eye-movement period. All GHRP injections were immediately followed by transient prolactin elevations and by GH pulses of a magnitude within or around the upper limit of the physiological range. Except for a nonsignificant tendency to increased amounts of wakefulness during the 1st h after the injection, no effects of GHRP-2 administration on sleep were detected. There was in particular no enhancement of SW sleep. Thus, in contrast to GHRH, late-night single injections of GHRP-2 at a dosage resulting in similar GH elevations have no stimulatory effects on SW sleep. The present data provide evidence against the involvement of the GHRP axis in human SW sleep regulation.
- Published
- 1998
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188. EEG sleep in non-affective psychiatric disorders.
- Author
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Kerkhofs M
- Abstract
Several sleep complaints and disturbances have been documented in psychiatric disorders. These modifications of sleep in anxiety disorders, alcoholism, schizophrenia, dementia and eating disorders are reviewed and discussed. At the present time, there is no evidence for any specific sleep pattern in non-affective psychiatric disorders. The co-morbidity of sleep disorders like sleep apnoea, periodic leg movements and parasomnia in psychiatric illness is not very well known at the present time.
- Published
- 1997
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189. [Sleep apnea and nocturnal ventilatory assistance (nCPAP): 5-year experience in the conventional system].
- Author
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Noseda A, Kempenaers C, Hoffmann G, Kerkhofs M, Le Bon O, Linkowski P, Jann E, Schmerber J, and Yernault JC
- Subjects
- Adult, Aged, Anthropometry, Combined Modality Therapy, Female, Humans, Male, Middle Aged, Patient Compliance, Polysomnography, Positive-Pressure Respiration adverse effects, Sleep Apnea Syndromes physiopathology, Home Care Services, Positive-Pressure Respiration methods, Sleep Apnea Syndromes therapy
- Abstract
The reimbursement of nasal continuous positive airway pressure (nCPAP) by the Belgian social security, via a conventional system, has made since 1991 this treatment available to an increasing number of patients having moderate to severe sleep apnoea hypopnoea syndrome (SAHS). We have reviewed our experience in prescribing domiciliary nCPAP from 1991 to 1995. Three hundred twenty-five subjects with SAHS, predominantly male (89%) and/or obese (77%) subjects, have benefited. Mean use of nCPAP machine, assessed by reading the time counter, amounted 4.7 h per 24 h, with only 23% of non-compliant patients (use < 3 h per 24 h). In 205 patients nCPAP was effective in controlling SAHS-related symptoms. Cure, with successful weaning from nCPAP, was obtained in 16 patients, as a result of marked weight loss in 13 of them. Forty-six non-compliant subjects were not allowed by the physician to go on, and 40 subjects left nCPAP because of intolerance. Finally, 10 patients abandoned nCPAP because of inefficacy, ascribed to some associated condition, being predominant, and 8 patients died. Our results suggest that domiciliary nCPAP is an effective treatment for SAHS in a majority of subjects, but that this kind of treatment is prescribed lifelong, unless there is a marked weight loss. The Belgian conventional system, as it requires a regular follow-up, contributes to keep non-compliance within acceptable limits.
- Published
- 1997
190. Sleep apnea after 1 year domiciliary nasal-continuous positive airway pressure and attempted weight reduction. Potential for weaning from continuous positive airway pressure.
- Author
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Noseda A, Kempenaers C, Kerkhofs M, Houben JJ, and Linkowski P
- Subjects
- Body Mass Index, Counseling, Diet, Reducing, Female, Follow-Up Studies, Gastroplasty, Humans, Male, Middle Aged, Oxyhemoglobins analysis, Patient Compliance, Polysomnography, Sleep Apnea Syndromes blood, Sleep Apnea Syndromes physiopathology, Sleep Stages, Ventilator Weaning, Home Care Services, Hospital-Based, Positive-Pressure Respiration methods, Sleep Apnea Syndromes therapy, Weight Loss
- Abstract
Study Objective: To assess the effect of 1 year of therapy for sleep apnea syndrome (SAS) combining domiciliary nasal-continuous positive airway pressure (N-CPAP) and attempted weight loss on the severity of disease and to evaluate the potential for weaning from continuous positive airway pressure (CPAP)., Methods and Procedures: Ninety-five patients having a baseline apnea hypopnea index (AHI) greater than 10/h were prescribed N-CPAP at home. Weight loss was attempted by dietary counseling and by single ring vertical gastroplasty in those patients with a body mass index (BMI) greater than 40 kg/m2. Subjects were asked to return after 1 year for a full-night polysomnography (PSG) without CPAP and the results were compared with baseline PSG., Results: Thirty-nine patients compliant to CPAP were evaluated. Weight had decreased from 108.3 +/- 29.0 to 99.7 +/- 17.7 kg as a result of dietary counseling (n = 36) or gastroplasty (n = 3). A significant improvement was found in AHI (66.5 +/- 28.7-->50.3 +/- 38.4/h; p < 0.05), maximal duration of apnea or hypopnea (66 +/- 22-->47 +/- 18 s; p < 0.001), minimal oxyhemoglobin saturation (62 +/- 16-->78 +/- 7%; p < 0.001), and stage shift index (SSI) (76 +/- 29-->62 +/- 28/h; p < 0.05). The drop in AHI correlated with the reduction in BMI (r = 0.47; p < 0.01) and with the decrease in SSI (r = 0.50; p < 0.001). Weaning from CPAP was proposed to six patients and succeeded in four (three with 29, 93, and 94 kg weight loss, respectively, and one subject with a normal unchanged weight)., Conclusion: In 39 patients with SAS, 1-year domiciliary N-CPAP combined with weight loss resulted in a significant improvement in breathing during sleep and in sleep fragmentation, as judged from PSG without CPAP. Four subjects were successfully weaned, three of whom had in parallel a substantial decrease in weight.
- Published
- 1996
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191. Acute, subchronic and withdrawal sleep EEG changes during treatment with paroxetine and amitriptyline: a double-blind randomized trial in major depression.
- Author
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Staner L, Kerkhofs M, Detroux D, Leyman S, Linkowski P, and Mendlewicz J
- Subjects
- Adolescent, Adult, Aged, Amitriptyline pharmacology, Double-Blind Method, Electroencephalography drug effects, Humans, Male, Middle Aged, Paroxetine adverse effects, Paroxetine pharmacology, Polysomnography, Sleep Stages drug effects, Sleep, REM drug effects, Wakefulness drug effects, Amitriptyline therapeutic use, Antidepressive Agents therapeutic use, Depressive Disorder drug therapy, Paroxetine therapeutic use, Selective Serotonin Reuptake Inhibitors therapeutic use
- Abstract
Paroxetine (30 mg), a selective serotonin (5-HT) reuptake inhibitor, was compared in a double-blind trial to amitriptyline (150 mg) in a sample of 40 inpatients aged 18-65 years who fulfilled Research Diagnostic Criteria for major depression. Patients were studied after a placebo drug washout period of 10 days and after an active 4-week treatment period. Sleep EEG recordings were performed before and at the end of the study as well as during acute treatment (first 2 days) and following withdrawal of active medication. Paroxetine shows an antidepressant effect similar to amitriptyline with a different side-effect profile typical of 5-HT reuptake inhibition. Paroxetine and amitriptyline decreased the amount of REM sleep, a well-known effect of classical antidepressants. Paroxetine also shared with other 5-HT reuptake inhibitors an alerting effect on sleep that was not shown to be detrimental on subjective sleep quality.
- Published
- 1995
192. The 24-hour profiles of cortisol, prolactin, and growth hormone secretion in mania.
- Author
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Linkowski P, Kerkhofs M, Van Onderbergen A, Hubain P, Copinschi G, L'Hermite-Balériaux M, Leclercq R, Brasseur M, Mendlewicz J, and Van Cauter E
- Subjects
- Acute Disease, Adolescent, Adult, Age Factors, Depressive Disorder blood, Humans, Male, Middle Aged, Polysomnography, Recurrence, Sleep physiology, Sleep, REM physiology, Bipolar Disorder blood, Circadian Rhythm, Growth Hormone blood, Hydrocortisone blood, Prolactin blood
- Abstract
Objective: To characterize sleep and the 24-hour profiles of cortisol, prolactin (PRL), and growth hormone (GH) secretion in mania., Methods: Blood was sampled at 15-minute intervals, and sleep was polygraphically recorded in eight unmedicated male patients with pure mania and the results compared with those from a group of 14 healthy age-matched controls. The circadian, sleep-related, and pulsatile hormonal variations were quantitatively characterized using specifically designed computer algorithms., Results: The manic state was associated with alterations of corticotropic activity and circadian rhythmicity partially overlapping those previously observed in acute endogenous depression, consisting of an elevation of nocturnal cortisol levels and an early timing of the nadir of the circadian variation. Sleep onset was delayed and the sleep period was reduced. A trend for short rapid eye movement latencies was apparent in the adult patients. Both the amount and the temporal organization of PRL and GH secretion were normal., Conclusion: The manic state seems to be characterized by similar but less severe neuroendocrine and circadian abnormalities, compared with major depression.
- Published
- 1994
- Full Text
- View/download PDF
193. Automatic analysis of pneumologic signals.
- Author
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Lanquart JP, Stanus E, Kerkhofs M, Linkowski P, and Mendlewicz J
- Subjects
- Humans, Signal Processing, Computer-Assisted, Sleep Stages physiology, Respiration, Sleep physiology
- Published
- 1994
194. Validation of the Newcastle Scale through sleep polysomnographic studies in major depression: comparison with age matched controls.
- Author
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Souery D, Hubain P, Joenck L, Van Veeren C, Kerkhofs M, Staner L, Mendlewicz J, and Linkowski P
- Subjects
- Depressive Disorder psychology, Humans, Male, Reproducibility of Results, Sleep, REM physiology, Depressive Disorder physiopathology, Neuropsychological Tests, Polysomnography
- Published
- 1994
195. Sleep EEG in psychotic and non psychotic depressive patients matched for age, gender and polarity.
- Author
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Stefos G, Staner L, Van Veeren C, Hubain P, Kerkhofs M, Linkowski P, and Mendlewicz J
- Subjects
- Depressive Disorder complications, Electroencephalography, Female, Humans, Male, Middle Aged, Psychotic Disorders complications, Sleep, REM physiology, Depressive Disorder physiopathology, Psychotic Disorders physiopathology, Sleep physiology
- Published
- 1994
196. [Comparative analysis of clinical and biological findings in major depression in unipolar and bipolar patients].
- Author
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Fossion P, Staner L, Hubain P, Kerkhofs M, Mendlewicz J, and Linkowski P
- Subjects
- Adult, Bipolar Disorder metabolism, Depressive Disorder metabolism, Dexamethasone, Female, Humans, Male, Neuropsychological Tests, Polysomnography, Thyrotropin-Releasing Hormone, Bipolar Disorder diagnosis, Depressive Disorder diagnosis
- Published
- 1994
197. Neuroendocrine and sleep variables in endogenous depression: the role of severity.
- Author
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Van Veeren C, Staner L, Hubain P, Kerkhofs M, Mendlewicz J, and Linkowski P
- Subjects
- Adolescent, Adult, Aged, Depressive Disorder physiopathology, Female, Humans, Hydrocortisone metabolism, Male, Middle Aged, Severity of Illness Index, Thyrotropin metabolism, Depressive Disorder metabolism, Neurosecretion
- Published
- 1994
198. Sleep-promoting effects of growth hormone-releasing hormone in normal men.
- Author
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Kerkhofs M, Van Cauter E, Van Onderbergen A, Caufriez A, Thorner MO, and Copinschi G
- Subjects
- Adult, Humans, Male, Reference Values, Sleep Stages drug effects, Sleep, REM drug effects, Time Factors, Growth Hormone-Releasing Hormone pharmacology, Sleep drug effects
- Abstract
Growth hormone-releasing hormone (GHRH) promotes rapid-eye-movement (REM) and non-REM sleep in animals, but there is little direct evidence for a hypnogenic action of GHRH in humans. In the present study, the possible somnogenic effects of intravenous bolus injections of a dose of GHRH eliciting physiological elevations of GH secretion in healthy young men were investigated. GHRH (0.3 micrograms/kg body wt) was given in early sleep [i.e., 1st slow-wave (SW) period], late sleep (i.e., 3rd REM period), and early sleep after sleep deprivation until 0400 h (i.e., 1st SW period). In the absence of sleep deprivation, injection of GHRH in early sleep did not modify SW sleep but increased REM sleep. GHRH administration in the third REM period was followed by a marked decrease of wake and an almost 10-fold increase in SW sleep. When GHRH was administered during the first SW period after sleep deprivation until 0400 h, the duration of wake decreased. Thus GHRH has sleep-promoting effects in young adults, particularly when given at a time of decreased sleep propensity.
- Published
- 1993
- Full Text
- View/download PDF
199. Twin study of the 24-h cortisol profile: evidence for genetic control of the human circadian clock.
- Author
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Linkowski P, Van Onderbergen A, Kerkhofs M, Bosson D, Mendlewicz J, and Van Cauter E
- Subjects
- Adolescent, Adult, Humans, Male, Pulsatile Flow, Time Factors, Circadian Rhythm, Genes, Hydrocortisone blood, Twins, Dizygotic, Twins, Monozygotic
- Abstract
To determine whether genetic factors control the expression of human circadian rhythmicity, we analyzed the 24-h profile of plasma cortisol in 11 monozygotic and 10 dizygotic pairs of normal male twins. Blood was sampled every 15 min, and sleep was monitored. Circadian rhythmicity was characterized by measures of amplitude, phase, and overall waveshape. Pulsatility was quantified by pulse frequency, pulse amplitude, and relative contribution of pulsatile vs. circadian variations. Data were analyzed by a procedure specifically developed for twin studies. Genetic control was demonstrated for the timing of the nocturnal nadir and for the proportion of overall temporal variability associated with pulsatility. Environmental effects were detected for the 24-h mean and the timing of the morning acrophase. The timing of the cortisol nadir is a robust marker of human circadian phase and is dependent, under entrained conditions, on the length of the endogenous period. Animal studies have shown that the endogenous period and the pattern of entrainment to exogenous 24-h periodicities are genetically controlled. Our results indicate that, despite the increased impact of social inputs, genetic factors also control human circadian rhythmicity.
- Published
- 1993
- Full Text
- View/download PDF
200. Biological and clinical features of recurrent brief depression: a comparison with major depressed and healthy subjects.
- Author
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Staner L, De La Fuente JM, Kerkhofs M, Linkowski P, and Mendlewicz J
- Subjects
- Adult, Bipolar Disorder diagnosis, Bipolar Disorder psychology, Depressive Disorder diagnosis, Depressive Disorder psychology, Female, Humans, Hypothalamo-Hypophyseal System physiopathology, Male, Middle Aged, Personality Inventory, Pituitary-Adrenal System physiopathology, Sleep Stages physiology, Thyroid Gland physiopathology, Bipolar Disorder physiopathology, Depressive Disorder physiopathology, Dexamethasone, Hydrocortisone blood, Polysomnography, Thyrotropin blood, Thyrotropin-Releasing Hormone
- Abstract
Recurrent brief depression (RBD) has recently been proposed as a new subtype of affective disorder characterized by episodes of major depression which last less than two weeks. The aim of this study was to further evaluate the validity of this putative subtype by means of clinical and biological data. DST, TSH response to TRH and sleep EEG variables were compared in 25 RBD patients sex- and age-matched to 25 major depressed (MD) and 25 healthy subjects. Family history, age at onset, and psychiatric comorbidity did not discriminate RBD from MD. Recurrent unipolar depression was found to be more prevalent in MD. Although less severely depressed during the biological tests, patients with RBD did not significantly differ from those with MDD on basis of DST non-suppression, blunted TSH response and shortening of REM latency. Compared to controls, a greater sleep onset latency was observed both in RBD and MD and a lower total sleep time in MD patients only. These results suggest that RBD could be viewed as a subtype of affective disorder sharing many characteristics with MDD.
- Published
- 1992
- Full Text
- View/download PDF
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