| 238571. |
- Rousseau, Andreas, 1971-, et al.
(författare)
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Acute hyperoxaemia-induced effects on regional blood flow, oxygen consumption and central circulation in man
- 2005
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772 .- 1365-201X. ; 183:3, s. 231-240
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Despite numerous in vitro and animal studies, circulatory effects and mechanisms responsible for the vasoconstriction seen during hyperoxaemia are yet to be ascertained. The present study set out to: (i) set up a non-invasive human model for the study of hyperoxia-induced cardiovascular effects, (ii) describe the dynamics of this effect and (iii) determine whether hyperoxaemia also, by vasoconstriction alters oxygen consumption (O2).Methods: The study comprised four experiments (A, B, C and D) on healthy volunteers examined before, during and after 100% oxygen breathing. A: Blood flow (mL min−1·100 mL−1 tissue), venous occlusion plethysmography was assessed (n = 12). B: Blood flow was recorded with increasing transcutaneous oxygen tension (PtcO2) levels (dose–response) (n = 8). C: Heart rate (HR), stroke volume, cardiac output (CO) and systemic vascular resistance (SVR) was assessed using echocardiography (n = 8). D: O2 was measured using an open circuit technique when breathing an air-O2 mix (fraction of inhaled oxygen: FiO2 = 0.58) (n = 8).Results: Calf blood flow decreased 30% during O2 breathing. The decrease in calf blood flow was found to be oxygen dose dependent. A similar magnitude, as for the peripheral circulation, of the effect on central parameters (HR/CO and SVR) and in the time relationship was noted. Hyperoxia did not change O2. An average of 207 (93) mL O2 per subject was washed in during the experiments.Conclusion: This model appears suitable for the investigation of O2-related effects on the central and peripheral circulation in man. Our findings, based on a more comprehensive (central/peripheral circulation examination) evaluation than earlier made, suggest significant circulatory effects of hyperoxia. Further studies are warranted to elucidate the underlying mechanisms.
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| 238572. |
- Rousseau, Andreas, 1971-, et al.
(författare)
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Hyperoxia decreases cutaneous blood flow in high-perfusion areas
- 2007
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Ingår i: Microvascular Research. - : Elsevier BV. - 0026-2862 .- 1095-9319. ; 74:1, s. 15-22
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism by which hyperoxia decreases blood flow is still not understood. Hyperoxemia-induced vasoconstriction is known to occur in many organs, including brain and retina, skeletal muscle, and myocardium. Whether this also occurs in skin is unknown.This study was conducted in healthy volunteers exposed intermittently to 100% oxygen (FIO2 1.0). Perfusion of forearm skin was measured by laser Doppler imaging (LDI). In series 1, it was measured in 7 subjects before, during, and after 15 min of oxygen breathing. In series 2, flow was measured, also during air and O2 breathing, after perfusion was raised by (a) sympathetic blockade (induced by a topically applied local anesthetic) (n = 9) and by (b) current-induced vasodilation (n = 8).In normal unperturbed skin, there was no significant change with hyperoxia. When basal perfusion was raised by topical anesthesia or by current, there was also no change in mean perfusion overall with hyperoxia. However, areas with the highest perfusion (upper decile) showed a significant perfusion decrement with hyperoxia (− 30% and − 20%, respectively; p < 0.001).Vasoconstriction with hyperoxia has been demonstrated in human skin. The fact that it is observed only when flow is increased above basal levels and then only in high-flow vessels suggests that cutaneous blood flow control is primarily regulated by variables other than oxygen.
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| 238573. |
- Rousset, C. I., et al.
(författare)
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A dual role for AMP-activated protein kinase (AMPK) during neonatal hypoxic-ischaemic brain injury in mice
- 2015
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042. ; 133:2, s. 242-252
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Tidskriftsartikel (refereegranskat)abstract
- Perinatal hypoxic-ischaemic encephalopathy (HIE) occurs in 1-2 in every 1000 term infants and the devastating consequences range from cerebral palsy, epilepsy and neurological deficit to death. Cellular damage post insult occurs after a delay and is mediated by a secondary neural energy failure. AMP-activated protein kinase (AMPK) is a sensor of cellular stress resulting from ATP depletion and/or calcium dysregulation, hallmarks of the neuronal cell death observed after HIE. AMPK activation has been implicated in the models of adult ischaemic injury but, as yet, there have been no studies defining its role in neonatal asphyxia. Here, we find that in anin vivo model of neonatal hypoxia-ischaemic and in oxygen/glucose deprivation in neurons, there is pathological activationof the calcium/calmodulin-dependent protein kinase kinase (CaMKK)-AMPK1 signalling pathway. Pharmacological inhibition of AMPK during the insult promotes neuronal survival but, conversely, inhibiting AMPK activity prior to the insult sensitizes neurons, exacerbating cell death. Our data have pathological relevance for neonatal HIE as prior sensitization such as exposure to bacterial infection (reported to reduce AMPK activity) produces a significant increase in injury.
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| 238574. |
- Rousset, Catherine I, et al.
(författare)
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Mitochondria and perinatal brain injury.
- 2012
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Ingår i: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954. ; 25 Suppl 1, s. 35-8
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Tidskriftsartikel (refereegranskat)abstract
- Secondary brain injury after hypoxia-ischemia is associated with delayed loss of high energy phosphates implicating bioenergetic mitochondrial failure at least partly related to deregulation of the energy sensor adenosine monophosphate-activated protein kinase. Furthermore, the toxic intracellular environment (accumulation of reactive oxygen/nitrosative species and intracellular calcium) during post-ischemic reperfusion triggers Bax-dependent mitochondrial permeabilization (MP) leading to activation of caspase-dependent and apoptosis-inducing factor dependent cell death. We still do not understand how MP is induced but some data suggest that mitochondrial fusion/fission as well as migration play a critical role. Mitochondrial dynamics also seem critical for brain development as genetic deficiency of proteins involved in mitochondrial fusion and fission results in malformations including microcephaly, abnormal brain development and dysmyelination. In this brief review, we update the critical role of mitochondria in brain development and the decision of cell fate after hypoxia-ischemia in the immature CNS.
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| 238575. |
- Roussos, Louis, et al.
(författare)
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A Study on the Outcome of Percutaneous Transluminal Renal Angioplasty in Patients with Renal Failure.
- 2006
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Ingår i: Nephron Clinical Practice. - : S. Karger AG. - 1660-2110. ; 104:3, s. 132-142
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Tidskriftsartikel (refereegranskat)abstract
- Background: The indications for percutaneous transluminal renal angioplasty (PTRA) in renovascular disease, as well as its benefits, remain a matter of debate. The aim of this study was to evaluate the outcome of angioplasty and to identify risk factors associated with less successful outcomes in patients with atheromatous renal artery stenosis and renal failure of varying degrees. Methods: The results of PTRA were analyzed retrospectively in 144 patients with serum creatinine levels of >130 µmol/l. Patients were divided into 5 groups according to their indication for angioplasty: (1) deteriorating renal function; (2) accelerating hypertension; (3) a combination of 1 and 2; (4) peripheral vascular disease, and (5) miscellaneous conditions. Results: The baseline mean (± SD) systolic and diastolic blood pressures of the entire group were lowered from 180 ± 32 and 95 ± 16 mm Hg to 162 ± 23 and 86 ± 12 mm Hg, respectively (p < 0.0005), 12 months after angioplasty. The blood pressure level was unaffected by angioplasty in patients with claudication. The mean number of antihypertensive drugs was reduced in the group with accelerating hypertension from 2.9 ± 0.8 to 2.4 ± 1.2 (p = 0.019), and in the group with unilateral renal artery stenosis and two kidneys from 2.4 ± 1.0 to 1.8 ± 1.1 (p = 0.002), 12 months after PTRA. Glomerular filtration rate at 3-month follow-up had increased from 23 ± 11 to 27 ± 14 ml/min/1.73 m2 (p = 0.021) in group 1, from 25 ± 11 to 28 ± 14 ml/min/1.73 m2 (p = 0.031) in the combined group of patients consisting of groups 1 and 3, and from 32 ± 13 to 35 ± 14 ml/min/1.73 m2 (p = 0.019) in the group with unilateral renal artery stenosis. No statistically significant difference was found in any of these 3 groups 1 year after angioplasty. The first patient group had an increased prevalence of cardiovascular disease, aortic aneurysm, carotid occlusive disease, and peripheral vascular disease compared to the other patient groups (p < 0.05). Patients with baseline creatinine levels of >300 µmol/l had a lower survival rate at 12, 60, and 120 months after PTRA than patients with serum creatinine levels of <300 µmol/l (p < 0.005). Survival was also lower in patients with bilateral renal artery stenosis and those with a single kidney, compared to patients with a unilateral stenosis at both 5 and 10 years after PTRA (p < 0.05). Regression analysis of predictor variables of mortality rate showed that the relative risk (RR) associated with increased serum creatinine was 4.7 (CI 2.0-11.0; p < 0.0005). The RR for older patients was 1.1 (CI 1.0-1.2; p = 0.008), and the RR for former smokers was 6.0 (CI 1.6-24.0; p = 0.009). Conclusion: The results of the present study indicate that glomerular filtration can be improved in patients who primarily undergo angioplasty to rescue renal function. Renal function with creatinine levels of >300 µmol/l was associated with a lower survival rate. It is, therefore, possible that patients selected after a thorough evaluation of their renal function and comorbid disease factors may benefit from PTRA, even when the indication for angioplasty is to salvage renal function.
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| 238576. |
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| 238577. |
- Roux, Barbara, et al.
(författare)
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Prescription and deprescription of medications for older adults receiving palliative care during the last 3months of life : a single-center retrospective cohort study
- 2019
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Ingår i: European Geriatric Medicine. - : Springer Science and Business Media LLC. - 1878-7649 .- 1878-7657. ; 10:3, s. 463-471
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Tidskriftsartikel (refereegranskat)abstract
- PurposeNear the end of life, drugs to ensure comfort and improve quality of life should be prioritized, and unnecessary drugs should be avoided. The aim was to assess the evolution and quality of drug therapy throughout the last 3 months of life of older adults in need of palliative care.MethodsA single-center retrospective cohort study included older adults (65years) who died in a teaching hospital between 1 January 2014 and 30 June 2014 and had been identified as patients in need of palliative care in their last 3 months of life. Drugs were collected from electronic medical records and defined as unnecessary' or essential' based on a review of the literature.ResultsA total of 149 patients were included [age: 82.1 (SD 8.6)years, women: 46.3%]. The mean number of medications varied from 6.7 (SD 3.3) drugs 90 days before death, to 7.5 (SD 4.1) 7 days before death, to 5.6 (SD 3.6) on the day of death. During the final week of life, one additional prescription of essential drugs was observed for 75.2% of patients and 79.3% of patients had at least one unnecessary drug deprescribed. The most prescribed and deprescribed drug classes were, respectively, analgesics (56.4%) and antithrombotic agents (38.2%) during the last week of life.ConclusionsNear the end of life, medication therapy is adapted to the goals of palliative care. However, this only occurs during the last week of life. Earlier transition to palliative care is necessary to avoid exposure to unnecessary drugs.
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| 238578. |
- Roux, Sandrine Le, et al.
(författare)
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Transforming Growth Factor Beta 1 Modulates the Functional Expression of the Neurokinin-1 Receptor in Human Keratocytes
- 2016
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 41:8, s. 1035-1043
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Transforming growth factor beta 1 (TGF-β1) is a cytokine involved in a variety of processes, such as differentiation of fibroblasts into myofibroblasts. TGF-β1 has also been shown to delay the internalization of the neurokinin-1 receptor (NK-1 R) after its activation by its ligand, the neuropeptide substance P (SP). NK-1 R comprises two naturally occurring variants, a full-length and a truncated form, triggering different cellular responses. SP has been shown to affect important events in the cornea - such as stimulating epithelial cell proliferation - processes that are involved in corneal wound healing and thus in maintaining the transparency of the corneal stroma. An impaired signaling through NK-1 R could thus impact the visual quality. We hypothesize that TGF-β1 modulates the expression pattern of NK-1 R in human corneal stroma cells, keratocytes. The purpose of this study was to test that hypothesis.METHODS: Cultures of primary keratocytes were set up with cells derived from healthy human corneas, obtained from donated transplantation graft leftovers, and characterized by immunocytochemistry and Western blot. Immunocytochemistry for TGF-β receptors and NK-1 R was performed. Gene expression was assessed with real-time polymerase chain reaction (qPCR).RESULTS: Expression of TGF-β receptors was confirmed in keratocytes in vitro. Treating the cells with TGF-β1 significantly reduced the gene expression of NK-1 R. Furthermore, immunocytochemistry for NK-1 R demonstrated that it is specifically the expression of the full-length isotype of the receptor that is reduced after treatment with TGF-β1, which was also confirmed with qPCR using a specific probe for the full-length receptor.CONCLUSIONS: TGF-β1 down-regulates the gene expression of the full-length variant of NK-1 R in human keratocytes, which might impact its signaling pathway and thus explain the known delay in internalization after activation by SP seen with TGF-β1 treatment.
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| 238579. |
- Rovira, P, et al.
(författare)
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Shared genetic background between children and adults with attention deficit/hyperactivity disorder
- 2020
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Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 1740-634X .- 0893-133X. ; 45:10, s. 1617-1626
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Tidskriftsartikel (refereegranskat)abstract
- Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.
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| 238580. |
- Rowe, Kirsten, et al.
(författare)
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Executive function in HIV-affected children and adolescents : a systematic review and meta-analyses
- 2021
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Ingår i: AIDS Care. - : Routledge. - 0954-0121 .- 1360-0451. ; 33:7, s. 833-857
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Tidskriftsartikel (refereegranskat)abstract
- This review aimed to determine: whether EF is affected in children and adolescents (2–24-years-old) with perinatal HIV infection, perinatal HIV exposure without infection, and behaviourally acquired HIV. A systematic review (PROSPERO number: CRD42017067813) was conducted using 11 electronic databases (01.01.1981–09.07.2019) and 8 conference websites. Primary quantitative studies with EF scores on cognitive tasks and/or behavioural report measures were included. Meta-analyses were performed by EF subtype and subpopulations compared. 1789 records were found. Sixty-one studies were included in the narrative synthesis; 32 (N = 7884 participants) were included in meta-analyses. There was a distinct pattern of reduced EF in those with perinatal HIV infection on antiretroviral therapy compared to controls: pooled effect sizes were largest for verbal and visuospatial working memory, with smaller effects on planning, inhibitory control and set-shifting. Data were limited for other HIV-affected subpopulations. Perinatal HIV infection is associated with reduced EF with varying effect sizes for the different EF subtypes.
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