272 results on '"Nicaise, C."'
Search Results
102. Modelling and treating amyotrophic lateral sclerosis through induced-pluripotent stem cells technology.
- Author
-
Bohl D, Pochet R, Mitrecic D, and Nicaise C
- Subjects
- Amyotrophic Lateral Sclerosis pathology, Animals, Cell Differentiation genetics, Disease Models, Animal, Humans, Motor Neurons transplantation, Amyotrophic Lateral Sclerosis therapy, Cellular Reprogramming, Induced Pluripotent Stem Cells transplantation, Stem Cell Transplantation
- Abstract
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease affecting primarily the population of motor neurons, even though a non-cell autonomous component, involving neighbouring non-neuronal cells, is more and more described. Despite 140 years of disease experience, still no efficient treatment exists against ALS. The inability to readily obtain the faulty cell types relevant to ALS has impeded progress in drug discovery for decades. However, the pioneer work of Shinya Yamanaka in 2007 in the stem cell field was a real breakthrough. Recent advances in cell reprogramming now grant access to significant quantities of CNS disease-affected cells. Induced pluripotent stem cells (iPSc) have been recently derived from patients carrying mutations linked to familial forms of ALS as well as from sporadic patients. Precise and mature protocols allow now their differentiation into ALS-relevant cell subtypes; sustainable and renewable sources of human motor neurons or glia are being available for ALS disease modelling, drug screening or for the development of cell therapies. In few years, the proof-of-concept was made that ALS disease-related phenotypes can be reproduced with iPSc and despite some remaining challenges, we are now not so far to provide platforms for the investigation of ALS therapeutics. This paper also reviews the pioneering studies regarding the applicability of iPSc technology in ALS animal models. From modest slowing down of ALS progression to no severe adverse effects, iPSc-based cell therapy resulted in promising premises in ALS preclinical paradigms, although long-term surveys are highly recommended.
- Published
- 2016
- Full Text
- View/download PDF
103. Translation of the focus toward excellence in translational science: comment on "TDP-43 Repression of Nonconserved Cryptic Exons is Compromised in ALS-FTD".
- Author
-
Pochet R, Nicaise C, and Mitrečić D
- Subjects
- Animals, Autophagy-Related Proteins, Cysteine Endopeptidases genetics, Embryonic Stem Cells, Exons genetics, Gene Knockout Techniques, HeLa Cells, Humans, Mice, Protein Isoforms genetics, RNA Splicing, RNA Stability, RNA, Messenger, Amyotrophic Lateral Sclerosis genetics, DNA-Binding Proteins genetics, Frontotemporal Dementia genetics
- Published
- 2015
- Full Text
- View/download PDF
104. Transplantation of stem cell-derived astrocytes for the treatment of amyotrophic lateral sclerosis and spinal cord injury.
- Author
-
Nicaise C, Mitrecic D, Falnikar A, and Lepore AC
- Abstract
Neglected for years, astrocytes are now recognized to fulfill and support many, if not all, homeostatic functions of the healthy central nervous system (CNS). During neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and spinal cord injury (SCI), astrocytes in the vicinity of degenerating areas undergo both morphological and functional changes that might compromise their intrinsic properties. Evidence from human and animal studies show that deficient astrocyte functions or loss-of-astrocytes largely contribute to increased susceptibility to cell death for neurons, oligodendrocytes and axons during ALS and SCI disease progression. Despite exciting advances in experimental CNS repair, most of current approaches that are translated into clinical trials focus on the replacement or support of spinal neurons through stem cell transplantation, while none focus on the specific replacement of astroglial populations. Knowing the important functions carried out by astrocytes in the CNS, astrocyte replacement-based therapies might be a promising approach to alleviate overall astrocyte dysfunction, deliver neurotrophic support to degenerating spinal tissue and stimulate endogenous CNS repair abilities. Enclosed in this review, we gathered experimental evidence that argue in favor of astrocyte transplantation during ALS and SCI. Based on their intrinsic properties and according to the cell type transplanted, astrocyte precursors or stem cell-derived astrocytes promote axonal growth, support mechanisms and cells involved in myelination, are able to modulate the host immune response, deliver neurotrophic factors and provide protective molecules against oxidative or excitotoxic insults, amongst many possible benefits. Embryonic or adult stem cells can even be genetically engineered in order to deliver missing gene products and therefore maximize the chance of neuroprotection and functional recovery. However, before broad clinical translation, further preclinical data on safety, reliability and therapeutic efficiency should be collected. Although several technical challenges need to be overcome, we discuss the major hurdles that have already been met or solved by targeting the astrocyte population in experimental ALS and SCI models and we discuss avenues for future directions based on latest molecular findings regarding astrocyte biology.
- Published
- 2015
- Full Text
- View/download PDF
105. Potential involvement of the IL-33-ST2 axis in the pathogenesis of primary Sjogren's syndrome.
- Author
-
Awada A, Nicaise C, Ena S, Schandéné L, Rasschaert J, Popescu I, Gangji V, and Soyfoo MS
- Subjects
- Case-Control Studies, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Humans, Immunohistochemistry, Interferon-gamma drug effects, Interferon-gamma metabolism, Interleukin-1 Receptor-Like 1 Protein, Interleukin-12 pharmacology, Interleukin-17 metabolism, Interleukin-23 pharmacology, Interleukin-33, Interleukins pharmacology, Killer Cells, Natural drug effects, Killer Cells, Natural metabolism, Lupus Erythematosus, Systemic metabolism, Male, Middle Aged, Natural Killer T-Cells drug effects, Natural Killer T-Cells metabolism, Sjogren's Syndrome etiology, Interleukins metabolism, Receptors, Cell Surface metabolism, Salivary Glands metabolism, Sjogren's Syndrome metabolism
- Abstract
Objectives: To investigate the role of the interleukin (IL)-33-ST2 axis in the pathophysiology of primary Sjögren's syndrome (pSS)., Methods: Serum levels of IL-33 and sST2 were determined by ELISA. The expression of IL-33 and ST2 was investigated in salivary glands (SG) by immunohistochemistry. PBMC were isolated and stimulated with IL-33, IL-12 and IL-23 and the cytokine profile response was examined by flow cytometry. Intracellular cytokine detection of IFNγ and IL-17 was performed by flow cytometry., Results: Serum IL-33 and sST2 levels were increased in pSS patients compared with controls and patients with systemic lupus erythematosus. Expression of IL-33 was upregulated in SG with Chisholm scores of 2 and 3 of pSS patients but comparable with controls for SG with Chisholm score of 4. ST2 expression in SG was downregulated in pSS patients. IL-33 at different concentrations did not increase the secretion of pro-inflammatory cytokines but acted synergistically with IL-12 and IL-23 to promote IFNγ production. NK and NKT cells were identified as main producers of IFNγ in vitro and were found in SG of pSS patients., Conclusions: IL-33 is released in pSS, and acts with IL-12 and IL-23 to favour the secretion of IFNγ by NK and NKT cells.
- Published
- 2014
- Full Text
- View/download PDF
106. Overexpression of the astrocyte glutamate transporter GLT1 exacerbates phrenic motor neuron degeneration, diaphragm compromise, and forelimb motor dysfunction following cervical contusion spinal cord injury.
- Author
-
Li K, Nicaise C, Sannie D, Hala TJ, Javed E, Parker JL, Putatunda R, Regan KA, Suain V, Brion JP, Rhoderick F, Wright MC, Poulsen DJ, and Lepore AC
- Subjects
- Animals, Astrocytes metabolism, Diaphragm physiopathology, Excitatory Amino Acid Transporter 2 genetics, Female, Forelimb metabolism, Gene Expression Regulation physiology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Motor Neurons pathology, Nerve Degeneration genetics, Nerve Degeneration pathology, Phrenic Nerve metabolism, Phrenic Nerve pathology, Rats, Rats, Sprague-Dawley, Spinal Cord Injuries genetics, Spinal Cord Injuries pathology, Astrocytes pathology, Cervical Vertebrae, Diaphragm metabolism, Excitatory Amino Acid Transporter 2 biosynthesis, Forelimb physiopathology, Motor Neurons metabolism, Nerve Degeneration metabolism, Spinal Cord Injuries metabolism
- Abstract
A major portion of spinal cord injury (SCI) cases affect midcervical levels, the location of the phrenic motor neuron (PhMN) pool that innervates the diaphragm. While initial trauma is uncontrollable, a valuable opportunity exists in the hours to days following SCI for preventing PhMN loss and consequent respiratory dysfunction that occurs during secondary degeneration. One of the primary causes of secondary injury is excitotoxic cell death due to dysregulation of extracellular glutamate homeostasis. GLT1, mainly expressed by astrocytes, is responsible for the vast majority of functional uptake of extracellular glutamate in the CNS, particularly in spinal cord. We found that, in bacterial artificial chromosome-GLT1-enhanced green fluorescent protein reporter mice following unilateral midcervical (C4) contusion SCI, numbers of GLT1-expressing astrocytes in ventral horn and total intraspinal GLT1 protein expression were reduced soon after injury and the decrease persisted for ≥6 weeks. We used intraspinal delivery of adeno-associated virus type 8 (AAV8)-Gfa2 vector to rat cervical spinal cord ventral horn for targeting focal astrocyte GLT1 overexpression in areas of PhMN loss. Intraspinal delivery of AAV8-Gfa2-GLT1 resulted in transduction primarily of GFAP(+) astrocytes that persisted for ≥6 weeks postinjury, as well as increased intraspinal GLT1 protein expression. Surprisingly, we found that astrocyte-targeted GLT1 overexpression increased lesion size, PhMN loss, phrenic nerve axonal degeneration, and diaphragm neuromuscular junction denervation, and resulted in reduced functional diaphragm innervation as assessed by phrenic nerve-diaphragm compound muscle action potential recordings. These results demonstrate that GLT1 overexpression via intraspinal AAV-Gfa2-GLT1 delivery exacerbates neuronal damage and increases respiratory impairment following cervical SCI., (Copyright © 2014 the authors 0270-6474/14/337622-17$15.00/0.)
- Published
- 2014
- Full Text
- View/download PDF
107. Immunohistochemical toolkit for tracking and quantifying xenotransplanted human stem cells.
- Author
-
Allard J, Li K, Lopez XM, Blanchard S, Barbot P, Rorive S, Decaestecker C, Pochet R, Bohl D, Lepore AC, Salmon I, and Nicaise C
- Subjects
- Animals, Heterografts, Humans, Immunohistochemistry methods, Male, Mice, Rats, Rats, Sprague-Dawley, Antigens, Differentiation metabolism, Cell Tracking methods, Induced Pluripotent Stem Cells cytology, Induced Pluripotent Stem Cells metabolism, Induced Pluripotent Stem Cells transplantation, Stem Cell Transplantation
- Abstract
Aim: Biomarker-based tracking of human stem cells xenotransplanted into animal models is crucial for studying their fate in the field of cell therapy or tumor xenografting., Materials & Methods: Using immunohistochemistry and in situ hybridization, we analyzed the expression of three human-specific biomarkers: Ku80, human mitochondria (hMito) and Alu., Results: We showed that Ku80, hMito and Alu biomarkers are broadly expressed in human tissues with no or low cross-reactivity toward rat, mouse or pig tissues. In vitro, we demonstrated that their expression is stable over time and does not change along the differentiation of human-derived induced pluripotent stem cells or human glial-restricted precursors. We tracked in vivo these cell populations after transplantation in rodent spinal cords using aforementioned biomarkers and human-specific antibodies detecting apoptotic, proliferating or neural-committed cells., Conclusion: This study assesses the human-species specificity of Ku80, hMito and Alu, and proposes useful biomarkers for characterizing human stem cells in xenotransplantation paradigms.
- Published
- 2014
- Full Text
- View/download PDF
108. Spontaneous regression of multiple Rasmussen aneurysms in a child with Lemierre syndrome and pulmonary abscesses.
- Author
-
Horwitz M, Chaumoître K, Grimaldi C, Retornaz K, Nicaise C, Thomachot L, Martin C, and Michel F
- Subjects
- Adolescent, Humans, Male, Remission, Spontaneous, Tomography, X-Ray Computed, Aneurysm, False pathology, Lemierre Syndrome pathology, Lung Abscess pathology
- Published
- 2013
- Full Text
- View/download PDF
109. Achieving parenteral nutrition goals in the critically ill newborns: standardized better than individualized formulations?
- Author
-
Doublet J, Vialet R, Nicaise C, Loundou A, Martin C, and Michel F
- Subjects
- Critical Illness, Humans, Infant, Newborn, Prescriptions, Retrospective Studies, Parenteral Nutrition, Total standards
- Abstract
Aim: The aim of this paper was to determine if the total parenteral nutrition (PN) goals for newborns in the first two weeks of lifer were better achieved with individualized prescriptions (IND-PN) or standardized formulations STD-PN prescriptions., Methods: A retrospective study was conducted in a 16-bed polyvalent pediatric and neonatal intensive care unit in a university hospital, to compare two one-year periods, before and after a move from individualized to standardized formulations. All the prescriptions for newborns who were admitted to our unit on their first day of life and required total PN were evaluated. The primary end-point was the percentage of prescriptions full filling the PN goals defined in the written policy of our unit., Results: More than 3500 prescriptions were included. The goals of PN were better achieved with STD-PN (44.0% vs. 9.4% of the prescriptions)., even after adjustment for term and birth weight. Differences between groups appeared as early as the third day of PN and remained during the first 15 days of PN., Conclusion: The goals of total PN were better achieved with STD-PN. Perhaps because standardized formulations contain fixed and proportional amounts of nutrients, their use results in less deviation from the established policy.
- Published
- 2013
110. Early phrenic motor neuron loss and transient respiratory abnormalities after unilateral cervical spinal cord contusion.
- Author
-
Nicaise C, Frank DM, Hala TJ, Authelet M, Pochet R, Adriaens D, Brion JP, Wright MC, and Lepore AC
- Subjects
- Animals, Cervical Vertebrae, Diaphragm pathology, Disease Models, Animal, Female, Phrenic Nerve physiopathology, Rats, Rats, Sprague-Dawley, Recovery of Function physiology, Respiration Disorders pathology, Spinal Cord Injuries pathology, Spinal Cord Injuries physiopathology, Diaphragm innervation, Motor Neurons pathology, Phrenic Nerve pathology, Respiration Disorders etiology, Spinal Cord Injuries complications
- Abstract
Contusion-type cervical spinal cord injury (SCI) is one of the most common forms of SCI observed in patients. In particular, injuries targeting the C3-C5 region affect the pool of phrenic motor neurons (PhMNs) that innervates the diaphragm, resulting in significant and often chronic respiratory dysfunction. Using a previously described rat model of unilateral midcervical C4 contusion with the Infinite Horizon Impactor, we have characterized the early time course of PhMN degeneration and consequent respiratory deficits following injury, as this knowledge is important for designing relevant treatment strategies targeting protection and plasticity of PhMN circuitry. PhMN loss (48% of the ipsilateral pool) occurred almost entirely during the first 24 h post-injury, resulting in persistent phrenic nerve axonal degeneration and denervation at the diaphragm neuromuscular junction (NMJ). Reduced diaphragm compound muscle action potential amplitudes following phrenic nerve stimulation were observed as early as the first day post-injury (30% of pre-injury maximum amplitude), with slow functional improvement over time that was associated with partial reinnervation at the diaphragm NMJ. Consistent with ipsilateral diaphragmatic compromise, the injury resulted in rapid, yet only transient, changes in overall ventilatory parameters measured via whole-body plethysmography, including increased respiratory rate, decreased tidal volume, and decreased peak inspiratory flow. Despite significant ipsilateral PhMN loss, the respiratory system has the capacity to quickly compensate for partially impaired hemidiaphragm function, suggesting that C4 hemicontusion in rats is a model of SCI that manifests subacute respiratory abnormalities. Collectively, these findings demonstrate significant and persistent diaphragm compromise in a clinically relevant model of midcervical contusion SCI; however, the therapeutic window for PhMN protection is restricted to early time points post-injury. On the contrary, preventing loss of innervation by PhMNs and/or inducing plasticity in spared PhMN axons at the diaphragm NMJ are relevant long-term targets.
- Published
- 2013
- Full Text
- View/download PDF
111. Neural progenitors derived from human induced pluripotent stem cells survive and differentiate upon transplantation into a rat model of amyotrophic lateral sclerosis.
- Author
-
Popescu IR, Nicaise C, Liu S, Bisch G, Knippenberg S, Daubie V, Bohl D, and Pochet R
- Subjects
- Amyotrophic Lateral Sclerosis metabolism, Amyotrophic Lateral Sclerosis pathology, Animals, Biomarkers metabolism, Cell Survival, Cells, Cultured, Disease Models, Animal, Feasibility Studies, Humans, Induced Pluripotent Stem Cells metabolism, Microtubule-Associated Proteins metabolism, Mutation, Neural Stem Cells metabolism, Neurons metabolism, Neurons pathology, Phenotype, Rats, Rats, Sprague-Dawley, Rats, Transgenic, Superoxide Dismutase genetics, Time Factors, Amyotrophic Lateral Sclerosis surgery, Induced Pluripotent Stem Cells transplantation, Neural Stem Cells transplantation, Neurogenesis, Neurons transplantation
- Abstract
Human induced pluripotent stem cells (iPSCs) offer hope for personalized regenerative cell therapy in amyotrophic lateral sclerosis (ALS). We analyzed the fate of human iPSC-derived neural progenitors transplanted into the spinal cord of wild-type and transgenic rats carrying a human mutated SOD1(G93A) gene. The aim was to follow survival and differentiation of human neural progenitors until day 60 post-transplantation in two different in vivo environments, one being ALS-like. iPSC-derived neural progenitors efficiently engrafted in the adult spinal cord and survived at high numbers. Different neural progenitor, astroglial, and neuronal markers indicated that, over time, the transplanted nestin-positive cells differentiated into cells displaying a neuronal phenotype in both wild-type and transgenic SOD1 rats. Although a transient microglial phenotype was detected at day 15, astroglial staining was negative in engrafted cells from day 1 to day 60. At day 30, differentiation toward a neuronal phenotype was identified, which was further established at day 60 by the expression of the neuronal marker MAP2. A specification process into motoneuron-like structures was evidenced in the ventral horns in both wild-type and SOD1 rats. Our results demonstrate proof-of-principle of survival and differentiation of human iPSC-derived neural progenitors in in vivo ALS environment, offering perspectives for the use of iPSC-based therapy in ALS.
- Published
- 2013
- Full Text
- View/download PDF
112. Comparison of GLUT1, GLUT2, GLUT4 and SGLT1 mRNA expression in the salivary glands and six other organs of control, streptozotocin-induced and Goto-Kakizaki diabetic rats.
- Author
-
Jurysta C, Nicaise C, Giroix MH, Cetik S, Malaisse WJ, and Sener A
- Subjects
- Animals, Blood Glucose analysis, Body Weight, Diabetes Mellitus, Experimental metabolism, Diabetes Mellitus, Experimental pathology, Gene Expression Regulation, Glucose Transport Proteins, Facilitative genetics, Glucose Transporter Type 1 genetics, Glucose Transporter Type 4 genetics, Rats, Real-Time Polymerase Chain Reaction, Sodium-Glucose Transporter 1 genetics, Glucose Transport Proteins, Facilitative metabolism, Glucose Transporter Type 1 metabolism, Glucose Transporter Type 4 metabolism, RNA, Messenger metabolism, Salivary Glands metabolism, Sodium-Glucose Transporter 1 metabolism
- Abstract
Background/aims: The expression and localization of several distinct glucose transporters (GLUT1, GLUT2, GLUT4, and SGLT1) was recently characterized in the parotid gland of normal rats by quantitative real-time PCR analysis, immunohistochemistry and Western blotting. The major aims of the present study was to compare the mRNA expression of these glucose transporters in both the parotid gland and submaxillary gland of control rats, streptozotocin-induced diabetic rats and hereditarily diabetic Goto-Kakizaki rats., Methods: Quantitative real-time PCR analysis was performed in the parotid and submaxillary salivary glands and, for purpose of comparison, also in the heart, kidney, liver, lung, muscle and pancreas from control animals and either streptozotocin-treated or Goto-Kakizaki rats., Results: The expression of GLUT4, but not GLUT1 or SGLT1, mRNA was decreased in the diabetic rats. The results also allow comparing both the mRNA expression level of the four glucose transporters in salivary glands and six other organs, and the diabetes-induced changes in such an expression in distinct locations., Conclusion: The mRNA expression of the insulin-dependent GLUT4 transporter was the sole to be significantly decreased in the salivary glands of diabetic animals. The possible consequence of such a decrease in terms of the control of salivary glucose concentration requires further investigation., (Copyright © 2012 S. Karger AG, Basel.)
- Published
- 2013
- Full Text
- View/download PDF
113. Degeneration of phrenic motor neurons induces long-term diaphragm deficits following mid-cervical spinal contusion in mice.
- Author
-
Nicaise C, Putatunda R, Hala TJ, Regan KA, Frank DM, Brion JP, Leroy K, Pochet R, Wright MC, and Lepore AC
- Subjects
- Action Potentials physiology, Algorithms, Animals, Axons pathology, Brain pathology, Cell Count, Cholera Toxin, Contusions pathology, Electromyography, Fluorescent Dyes, Male, Mice, Mice, Inbred C57BL, Neuromuscular Junction pathology, Survival, Cervical Vertebrae injuries, Diaphragm pathology, Motor Neurons pathology, Nerve Degeneration pathology, Phrenic Nerve pathology, Spinal Cord Injuries pathology
- Abstract
A primary cause of morbidity and mortality following cervical spinal cord injury (SCI) is respiratory compromise, regardless of the level of trauma. In particular, SCI at mid-cervical regions targets degeneration of both descending bulbospinal respiratory axons and cell bodies of phrenic motor neurons, resulting in deficits in the function of the diaphragm, the primary muscle of inspiration. Contusion-type trauma to the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron-diaphragm circuitry. We have generated a mouse model of cervical contusion SCI that unilaterally targets both C4 and C5 levels, the location of the phrenic motor neuron pool, and have examined histological and functional outcomes for up to 6 weeks post-injury. We report that phrenic motor neuron loss in cervical spinal cord, phrenic nerve axonal degeneration, and denervation at diaphragm neuromuscular junctions (NMJ) resulted in compromised ipsilateral diaphragm function, as demonstrated by persistent reduction in diaphragm compound muscle action potential amplitudes following phrenic nerve stimulation and abnormalities in spontaneous diaphragm electromyography (EMG) recordings. This injury paradigm is reproducible, does not require ventilatory assistance, and provides proof-of-principle that generation of unilateral cervical contusion is a feasible strategy for modeling diaphragmatic/respiratory deficits in mice. This study and its accompanying analyses pave the way for using transgenic mouse technology to explore the function of specific genes in the pathophysiology of phrenic motor neuron degeneration and respiratory dysfunction following cervical SCI.
- Published
- 2012
- Full Text
- View/download PDF
114. Comparison of ultrasound and X-ray in determining the position of umbilical venous catheters.
- Author
-
Michel F, Brevaut-Malaty V, Pasquali R, Thomachot L, Vialet R, Hassid S, Nicaise C, Martin C, and Panuel M
- Subjects
- Humans, Infant, Newborn, Intensive Care Units, Neonatal, Sensitivity and Specificity, Catheterization, Peripheral, Radiography, Interventional, Ultrasonography, Interventional, Umbilical Veins diagnostic imaging
- Abstract
Objective: Thoraco-abdominal X-ray (TAX) is the most frequent used method to determine the route and tip position (TP) of umbilical venous catheters (UVCs). The aim of this study was to compare ability of TAX and ultrasonography (US) to determine UVC route and TP., Patients and Methods: All neonates requiring UVC or admitted to our Paediatric and Neonatal Intensive Care with UVC were included in this prospective study. Catheter position was controlled by TAX and interpreted by the physician in charge of the patient. US examinations were performed by a paediatric radiologist blinded to TAX result. The UVC route (central or not central) and TP determined by each method were compared to the "actual UVC route and TP", as determined by senior paediatric radiologist and neonatologist referents joint interpretation of TAX and US results., Results: Sixty-one UVCs were assessed in 60 neonates of mean gestational age of 34.7±4.2 weeks. To determine catheter route, sensitivity and specificity were respectively 96.4% and 93.9% for US and 92.8% and 78.8% for TAX. To determine catheter tip position, sensitivity and specificity were respectively 93.3% and 95.6% for US and 66.7% and 63.0% for TAX (p<0.001). Failure of TAX to define UVC tip position increased with birth weight (p<0.005)., Conclusion: TAX and US are reliable in determining UVC route (central or not) but US examination is superior to TAX in determining UVC TP., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
115. Phrenic motor neuron degeneration compromises phrenic axonal circuitry and diaphragm activity in a unilateral cervical contusion model of spinal cord injury.
- Author
-
Nicaise C, Hala TJ, Frank DM, Parker JL, Authelet M, Leroy K, Brion JP, Wright MC, and Lepore AC
- Subjects
- Animals, Axons physiology, Cervical Vertebrae pathology, Diaphragm innervation, Diaphragm physiopathology, Female, Motor Neurons pathology, Motor Neurons physiology, Nerve Degeneration physiopathology, Nerve Net pathology, Nerve Net physiopathology, Phrenic Nerve physiology, Rats, Rats, Sprague-Dawley, Respiratory Paralysis pathology, Respiratory Paralysis physiopathology, Spinal Cord Injuries physiopathology, Axons pathology, Diaphragm pathology, Disease Models, Animal, Nerve Degeneration pathology, Phrenic Nerve pathology, Spinal Cord Injuries pathology
- Abstract
Respiratory dysfunction is the leading cause of morbidity and mortality following traumatic spinal cord injury (SCI). Injuries targeting mid-cervical spinal cord regions affect the phrenic motor neuron pool that innervates the diaphragm, the primary respiratory muscle of inspiration. Contusion-type injury in the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron-diaphragm circuitry. In an attempt to target the phrenic motor neuron pool, two unilateral contusion injury paradigms were tested, a single injury at level C4 and a double injury both at levels C3 and C4, and animals were followed for up to 6 weeks post-injury. Both unilateral cervical injury paradigms are reproducible with no mortality or need for breathing assistance, and are accompanied by phrenic motor neuron loss, phrenic nerve axon degeneration, diaphragm atrophy, denervation and subsequent partial reinnervation at the diaphragm neuromuscular junction, changes in spontaneous diaphragm EMG recordings, and reduction in phrenic nerve compound muscle action potential amplitude. These findings demonstrate significant and chronically persistent respiratory compromise following mid-cervical SCI due to phrenic motor neuron degeneration. These injury paradigms and accompanying analyses provide important tools both for understanding mechanisms of phrenic motor neuron and diaphragm pathology following SCI and for evaluating therapeutic strategies in clinically relevant cervical SCI models., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
116. Levels of kinesin light chain and dynein intermediate chain are reduced in the frontal cortex in Alzheimer's disease: implications for axoplasmic transport.
- Author
-
Morel M, Héraud C, Nicaise C, Suain V, and Brion JP
- Subjects
- Aged, Aged, 80 and over, Cell Line, Female, Frontal Lobe metabolism, Glycogen Synthase Kinase 3 metabolism, Glycogen Synthase Kinase 3 beta, Humans, Male, Neurofibrillary Tangles metabolism, Synaptophysin metabolism, tau Proteins metabolism, Alzheimer Disease metabolism, Axonal Transport physiology, Cerebellar Cortex metabolism, Dyneins metabolism, Kinesins metabolism
- Abstract
Fast anterograde and retrograde axoplasmic transports in neurons rely on the activity of molecular motors and are critical for maintenance of neuronal and synaptic functions. Disturbances of axoplasmic transport have been identified in Alzheimer's disease and in animal models of this disease, but their mechanisms are not well understood. In this study we have investigated the distribution and the level of expression of kinesin light chains (KLCs) (responsible for binding of cargos during anterograde transport) and of dynein intermediate chain (DIC) (a component of the dynein complex during retrograde transport) in frontal cortex and cerebellar cortex of control subjects and Alzheimer's disease patients. By immunoblotting, we found a significant decrease in the levels of expression of KLC1 and 2 and DIC in the frontal cortex, but not in the cerebellar cortex, of Alzheimer's disease patients. A significant decrease in the levels of synaptophysin and of tubulin-β3 proteins, two neuronal markers, was also observed. KLC1 and DIC immunoreactivities did not co-localize with neurofibrillary tangles. The mean mRNA levels of KLC1, 2 and DIC were not significantly different between controls and AD patients. In SH-SY5Y neural cells, GSK-3β phosphorylated KLC1, a change associated to decreased association of KLC1 with its cargoes. Increased levels of active GSK-3β and of phosphorylated KLC1 were also observed in AD frontal cortex. We suggest that reduction of KLCs and DIC proteins in AD cortex results from both reduced expression and neuronal loss, and that these reductions and GSK-3β-mediated phosphorylation of KLC1 contribute to disturbances of axoplasmic flows and synaptic integrity in Alzheimer's disease.
- Published
- 2012
- Full Text
- View/download PDF
117. Genetically modified stem cells for the treatment of neurological diseases.
- Author
-
Mitrecic D, Nicaise C, Klimaschewski L, Gajovic S, Bohl D, and Pochet R
- Subjects
- Cell Differentiation, Humans, Nervous System Diseases pathology, Stroke surgery, Nervous System Diseases surgery, Stem Cell Transplantation
- Abstract
The central nervous system has a very poor regenerative potential and is difficult to access. This partly explains why neurological diseases often lack appropriate therapeutic options and represent the most significant burden for healthcare systems. Progress in understanding the molecular background of neurological diseases requires innovative approaches offering new hope for the patients. One of the most intriguing and promising options is the combination of stem cells with gene therapy. Unlike fibroblasts, stem cells exhibit a high tropism for disease-affected tissue and integrate into the nervous tissue. This makes them ideal candidates for the production and delivery of molecules of interest for treating the nervous system. This article reviews the methodology for obtaining pluripotent stem cells (iPSCs) as precursors for neuronal cells, glial cells and the current state of the art in applications of genetically modified stem cells in animal models of neurodegenerative diseases, stroke, axonal damage, tumors and epilepsy.
- Published
- 2012
- Full Text
- View/download PDF
118. Glucose transport by acinar cells in rat parotid glands.
- Author
-
Jurysta C, Nicaise C, Cetik S, Louchami K, Malaisse WJ, and Sener A
- Subjects
- Acinar Cells cytology, Animals, Biological Transport, Cell Membrane metabolism, Female, Gene Expression Regulation, Glucose Transport Proteins, Facilitative genetics, Glucose Transporter Type 1 genetics, Glucose Transporter Type 1 metabolism, Glucose Transporter Type 2 genetics, Glucose Transporter Type 2 metabolism, Immunohistochemistry, Kidney cytology, Kidney metabolism, Pancreas cytology, Pancreas metabolism, Parotid Gland cytology, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, Sodium-Glucose Transporter 1 genetics, Sodium-Potassium-Exchanging ATPase metabolism, Acinar Cells metabolism, Glucose metabolism, Glucose Transport Proteins, Facilitative metabolism, Parotid Gland metabolism, Sodium-Glucose Transporter 1 metabolism
- Abstract
Background/aims: Salivary glucose is often considered as being from glandular origin. Little information is available, however, on the possible role of glucose transporters in the secretion of the hexose by salivary glands. The major aim of the present study was to investigate the expression and localization of several distinct glucose transporters in acinar cells of rat parotid glands., Methods: Quantitative real-time PCR analysis, immunohistochemistry and western blotting techniques were used to assess the presence of SGLT1, GLUT1, GLUT2 and GLUT4 in acinar cells of rat parotid glands., Results: Quantitative real-time PCR documented the expression of SGLT1 and GLUT1 in parotid tissues, with a much lower level of GLUT4 mRNA and no expression of GLUT2 mRNA. Western blot analysis revealed the presence of SGLT1, GLUT1 and GLUT4 proteins, but not GLUT2 proteins in the parotid extract. Immunohistochemistry confirmed these findings. SGLT1 was specifically located at the baso-lateral membrane, co-localizing with Na(+)/K(+) ATPase. GLUT1 was found both at the baso-lateral and apical level. GLUT4 appeared to be also located at the baso-lateral level. However, too little GLUT4 was present to allow co-localization labeling., Conclusion: Based on these findings, a model is proposed for the transport of glucose into the acinar cells and thereafter into the acinar lumen., (Copyright © 2012 S. Karger AG, Basel.)
- Published
- 2012
- Full Text
- View/download PDF
119. [Cellular transdifferentiation in amyotrophic lateral sclerosis].
- Author
-
Nicaise C, Bohl D, and Pochet R
- Subjects
- Animals, Cell Transdifferentiation, Humans, Induced Pluripotent Stem Cells cytology
- Published
- 2011
- Full Text
- View/download PDF
120. Astrocytes are an early target in osmotic demyelination syndrome.
- Author
-
Gankam Kengne F, Nicaise C, Soupart A, Boom A, Schiettecatte J, Pochet R, Brion JP, and Decaux G
- Subjects
- Animals, Astrocytes metabolism, Astrocytes pathology, Blood-Brain Barrier pathology, Cell Death drug effects, Connexins metabolism, Demyelinating Diseases blood, Demyelinating Diseases pathology, Disease Models, Animal, Down-Regulation drug effects, Gene Expression Regulation, Hypertrophy chemically induced, Hyponatremia blood, Lymphocytes drug effects, Male, Microglia drug effects, Myelin Sheath pathology, Nerve Growth Factors metabolism, Neutrophil Infiltration drug effects, Osmotic Pressure, Rats, Rats, Wistar, S100 Calcium Binding Protein beta Subunit, S100 Proteins metabolism, Sodium blood, Astrocytes drug effects, Demyelinating Diseases chemically induced, Hyponatremia drug therapy, Saline Solution, Hypertonic adverse effects
- Abstract
Abrupt osmotic changes during rapid correction of chronic hyponatremia result in demyelinative brain lesions, but the sequence of events linking rapid osmotic changes to myelin loss is not yet understood. Here, in a rat model of osmotic demyelination syndrome, we found that massive astrocyte death occurred after rapid correction of hyponatremia, delineating the regions of future myelin loss. Astrocyte death caused a disruption of the astrocyte-oligodendrocyte network, rapidly upregulated inflammatory cytokines genes, and increased serum S100B, which predicted clinical manifestations and outcome of osmotic demyelination. These results support a model for the pathophysiology of osmotic brain injury in which rapid correction of hyponatremia triggers apoptosis in astrocytes followed by a loss of trophic communication between astrocytes and oligodendrocytes, secondary inflammation, microglial activation, and finally demyelination.
- Published
- 2011
- Full Text
- View/download PDF
121. Apparent life-threatening events in presumably healthy newborns during early skin-to-skin contact.
- Author
-
Andres V, Garcia P, Rimet Y, Nicaise C, and Simeoni U
- Subjects
- Asphyxia Neonatorum mortality, Breast Feeding, Cause of Death, Cerebral Hemorrhage etiology, Cerebral Hemorrhage mortality, Cross-Sectional Studies, Delivery Rooms, Diseases in Twins, Female, France, Heart Arrest etiology, Heart Arrest mortality, Humans, Hypoxia-Ischemia, Brain etiology, Hypoxia-Ischemia, Brain mortality, Incidence, Infant, Newborn, Male, Postpartum Period, Resuscitation, Risk Factors, Asphyxia Neonatorum etiology, Prone Position, Sudden Infant Death etiology
- Abstract
The death or near death of a presumably healthy newborn in the delivery room is uncommon. We report here 6 cases of apparent life-threatening events (ALTEs) in the delivery room during the first 2 hours of life. In each case, the incident occurred in a healthy infant who was in a prone position on his or her mother's abdomen during early skin-to-skin contact. In most cases, the mother was primiparous, and in all cases the mother and infant were not observed during the initiation of skin-to-skin contact and breastfeeding. There are many benefits of early skin-to-skin contact and breastfeeding in the delivery room. However, in view of the risk of a rare but significant ALTE, we suggest that surveillance of newborns is needed. Although many ALTEs are apparently caused by obstruction, we suggest that a standardized investigational workup be performed after an ALTE.
- Published
- 2011
- Full Text
- View/download PDF
122. Terlipressin as rescue therapy for refractory pulmonary hypertension in a neonate with a congenital diaphragmatic hernia.
- Author
-
Stathopoulos L, Nicaise C, Michel F, Thomachot L, Merrot T, Lagier P, and Martin C
- Subjects
- Antihypertensive Agents administration & dosage, Cause of Death, Delayed-Action Preparations, Drug Resistance, Fatal Outcome, Hernia, Diaphragmatic complications, Hernias, Diaphragmatic, Congenital, Humans, Hypertension, Pulmonary complications, Infant, Newborn, Infusions, Intravenous, Intensive Care Units, Neonatal, Male, Shock, Septic mortality, Treatment Outcome, Vasoconstrictor Agents administration & dosage, Vasoconstrictor Agents therapeutic use, Antihypertensive Agents therapeutic use, Hypertension, Pulmonary drug therapy
- Abstract
We report the case of a 38-week gestational age neonate, with isolated congenital diaphragmatic hernia presenting with refractory persistent pulmonary hypertension, systemic hypotension, and hypoxemia, resistant to usual therapeutics. Arginine vasopressin is responsible for systemic vasoconstriction and decreases pulmonary hypertension. We theorized that terlipressin, its long-acting analogue, could have the same properties. We used terlipressin as rescue therapy after parental and local ethics committee acceptance. After a bolus of terlipressin 20 μg/kg and continuous infusion at a rate of 5 μg/kg per hour, blood oxygen saturation improved from 75% to 98%, oxygen requirements fell from fraction of inspired oxygen 100% to 40%, and mean arterial pressure rose from 28 to 46 mm Hg, allowing a decrease of vasopressor infusion. Terlipressin may be useful in the management of neonates with congenital diaphragmatic hernia and refractory pulmonary hypertension., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
123. [Management of newborns with meconium-stained amniotic fluid: prospective evaluation of practice].
- Author
-
Michel F, Nicaise C, Camus T, Di-Marco JN, Thomachot L, Vialet R, Martin C, and Lagier P
- Subjects
- Female, Guideline Adherence, Humans, Infant, Newborn, Male, Prospective Studies, Suction, Amniotic Fluid, Infant, Newborn, Diseases therapy, Meconium
- Abstract
Objective: Regional guideline for immediate tracheal suctioning (ITS) in vigorous and non-vigorous infants born through meconium-stained amniotic fluid (MSAF) has been established in 2003. The objective of this study was to evaluate guideline application., Study Design: Prospective cohort., Patients and Methods: The first part of the study was a short survey about ITS practices in maternity hospitals then, management and early evolution of babies born through particulate MSAF was evaluated by questionnaire., Results: Among 6761 neonates, 199 (3%) were born with MSAF. Early clinical evaluation showed 52 (26%) non-vigorous neonates; 22 of them (42%) have had an ITS. One hundred and forty-seven neonates were vigorous (74%); 27 of them (18%) have had an ITS. Implementation of recommendations in non-vigorous babies was better in maternities of level III, while they were lower in maternities of level IIA for vigorous babies. Among 52 non-vigorous children, eight had a meconium aspiration syndrome (MAS), including five who had an ITS. One MAS occurred in vigorous babies but infection could not be excluded., Conclusion: Recommendations for ITS were implemented in 70% of cases but only in 42% of cases in non-vigorous babies. We have to improve formation and circulation of new recommendations., (Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
124. Sevoflurane for central catheter placement in neonatal intensive care: a randomized trial.
- Author
-
Michel F, Vialet R, Hassid S, Nicaise C, Garbi A, Thomachot L, DI Marco JN, Lagier P, and Martin C
- Subjects
- Blood Glucose metabolism, Feasibility Studies, Female, Gestational Age, Glucose, Hemodynamics physiology, Humans, Infant, Newborn, Infant, Premature, Male, Pain prevention & control, Pain Measurement drug effects, Prospective Studies, Respiratory Mechanics physiology, Sevoflurane, Sucking Behavior, Treatment Outcome, Anesthetics, Inhalation adverse effects, Catheterization, Central Venous adverse effects, Intensive Care, Neonatal, Methyl Ethers adverse effects
- Abstract
Objective: To compare the efficacy and safety of sevoflurane deep sedation with glucose and nonnutritive sucking (GNNS) in reducing the duration of the procedure and in preventing pain-related effects during peripherally inserted central catheter (PICC) placement., Background: PICC placement in neonatal intensive care is a delicate and stressful procedure that requires pain prevention. GNNS has been recommended in this situation but remain often inefficient., Methods: We designed a randomized controlled study in a sixteen-bed pediatric and neonatal unit in a tertiary hospital. Fifty-nine neonates at >28 weeks of gestation with continuous positive airway pressure or invasive mechanical ventilation and requiring PICC placement were included. Patients were randomized to receive inhaled sevoflurane (IS) or glucose and non-nutritive sucking (GNNS). Procedural duration and conditions, hemodynamic and respiratory parameters, occurrence of movements and complications were compared (http://clinicaltrials.gov trial register no. NCT00420693)., Results: The two groups had similar demographics. There were no between-group differences in procedural duration (P = 0.84) despite greater immobility in IS group (P = 0.017). IS was also associated with fewer episodes of hypertension (P = 0.003), tachycardia (P < 0.001), and bradycardia (P = 0.02). Occurrences of hypotension were not different between the groups (P = 0.06). The GNNS group showed more desaturation during the 4 h after the procedure (P = 0.03). Complications during intensive care stay did not differ between groups., Conclusion: Inhaled sevoflurane does not make easier catheters placement but prevent pain-related symptoms. Because sevoflurane is responsible for hypotension, it requires careful monitoring and treatment adaptation.
- Published
- 2010
- Full Text
- View/download PDF
125. Aquaporin-4 as a potential marker of BBB disruption in ALS models.
- Author
-
Nicaise C, Soyfoo MS, Delporte C, and Pochet R
- Subjects
- Animals, Disease Models, Animal, Humans, Amyotrophic Lateral Sclerosis metabolism, Aquaporin 4 metabolism, Biomarkers metabolism, Blood-Brain Barrier metabolism
- Published
- 2010
- Full Text
- View/download PDF
126. Distribution, differentiation, and survival of intravenously administered neural stem cells in a rat model of amyotrophic lateral sclerosis.
- Author
-
Mitrecić D, Nicaise C, Gajović S, and Pochet R
- Subjects
- Amyotrophic Lateral Sclerosis metabolism, Amyotrophic Lateral Sclerosis pathology, Animals, Apoptosis physiology, Cell Differentiation physiology, Disease Models, Animal, Humans, Injections, Intravenous, Intermediate Filament Proteins biosynthesis, Nerve Tissue Proteins biosynthesis, Nestin, Neural Stem Cells metabolism, Neural Stem Cells pathology, Rats, Rats, Sprague-Dawley, Stem Cell Transplantation methods, Tumor Necrosis Factor-alpha pharmacology, Amyotrophic Lateral Sclerosis therapy, Neural Stem Cells cytology, Neural Stem Cells transplantation
- Abstract
The transplantation of neural stem cells (NSCs) is a challenging therapeutic strategy for the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). To provide insight into the potential of the intravenous delivery of NSCs, we evaluated the delivery of NSCs marked with green fluorescent protein to the central nervous system (CNS) via intravenous tail vein injections in an ALS model. The injected cell fates were followed 1, 3, and 7 days after transplantation. The highest efficiency of cell delivery to the CNS was found in symptomatic ALS (up to 13%), moderate in presymptomatic ALS (up to 6%), and the lowest in wild-type animals (up to 0.3%). NSCs injected into ALS animals preferentially colonized the motor cortex, hippocampus, and spinal cord, and their differentiation was characterized by a decrease of nestin expression and the appearance of MAP2-, GFAP-, O4-, and CD68-positive cells. Tumor necrosis factor (TNF) administration increased the CNS delivery of transplanted cells in wild-type and presymptomatic, but not ALS symptomatic animals. Moreover, a TNF-related increase in NSC differentiation and survival was detected. Apoptosis was detected as the main cause of the loss of transplanted cells and it was influenced by TNF. Although 3 days after TNF treatment cell death was accelerated, TNF slowed down apoptosis after 7 days. This study provides elementary facts about the process occurring after NSCs leave the blood stream and enter the nervous tissue affected by inflammation/degeneration, which should help facilitate the planning of future bench-to-bedside translational projects.
- Published
- 2010
- Full Text
- View/download PDF
127. Impaired blood-brain and blood-spinal cord barriers in mutant SOD1-linked ALS rat.
- Author
-
Nicaise C, Mitrecic D, Demetter P, De Decker R, Authelet M, Boom A, and Pochet R
- Subjects
- Agrin genetics, Agrin metabolism, Amyotrophic Lateral Sclerosis genetics, Amyotrophic Lateral Sclerosis metabolism, Animals, Astrocytes metabolism, Astrocytes pathology, Biomarkers, Blood-Brain Barrier metabolism, Brain Stem metabolism, Cell Shape, Disease Models, Animal, Endothelial Cells cytology, Enzyme-Linked Immunosorbent Assay, Evans Blue, Hemosiderin metabolism, Immunoglobulins metabolism, Immunohistochemistry, Membrane Proteins genetics, Membrane Proteins metabolism, Microscopy, Electron, Occludin, Phosphoproteins genetics, Phosphoproteins metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Rats, Transgenic, Reverse Transcriptase Polymerase Chain Reaction, Spinal Cord metabolism, Staining and Labeling, Zonula Occludens-1 Protein, Amyotrophic Lateral Sclerosis pathology, Blood-Brain Barrier pathology, Brain Stem pathology, Spinal Cord pathology, Superoxide Dismutase genetics
- Abstract
Blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) impairment is an additional accident occurring during the amyotrophic lateral sclerosis (ALS) progression. In this work, we aimed to decipher if BBB/BSCB leakage appeared before critical detrimental events and could serve as a marker preceding clinical symptoms. Three different BBB leakage markers: Evans blue, IgG and hemosiderin, were used to look at the SOD1-linked ALS rat model at presymptomatic and symptomatic stages. Although IgG and hemosiderin could be detected at presymptomatic stage, Evans blue extravasation which fits best with BBB/BSCB impairment could only be seen at symptomatic stages. BBB/BSCB impairment was further substantiate by showing at symptomatic stages decreased mRNA expression of ZO-1 and occludin as well as agrin, a basal membrane constituent. Electron microscopic data substantiate a toxic environment around endothelial cell and peri-vascular swollen astrocyte end-feet showing oedema-linked BBB opening.
- Published
- 2009
- Full Text
- View/download PDF
128. In vivo morphological changes in animal models of amyotrophic lateral sclerosis and Alzheimer's-like disease: MRI approach.
- Author
-
Andjus PR, Bataveljić D, Vanhoutte G, Mitrecic D, Pizzolante F, Djogo N, Nicaise C, Gankam Kengne F, Gangitano C, Michetti F, van der Linden A, Pochet R, and Bacić G
- Subjects
- Alzheimer Disease metabolism, Alzheimer Disease physiopathology, Amyotrophic Lateral Sclerosis metabolism, Amyotrophic Lateral Sclerosis physiopathology, Animals, Blood-Brain Barrier metabolism, Blood-Brain Barrier pathology, Blood-Brain Barrier physiopathology, Brain metabolism, Brain physiopathology, Chemotaxis, Leukocyte immunology, Disease Models, Animal, Encephalitis metabolism, Encephalitis pathology, Encephalitis physiopathology, Gliosis metabolism, Gliosis pathology, Gliosis physiopathology, Humans, Nerve Degeneration metabolism, Nerve Degeneration pathology, Nerve Degeneration physiopathology, Rats, Alzheimer Disease pathology, Amyotrophic Lateral Sclerosis pathology, Brain pathology, Magnetic Resonance Imaging methods
- Abstract
Magnetic resonance imaging (MRI) is the only noninvasive technique that provides structural information on both cell loss and metabolic changes. After reviewing all the results obtained in clinical studies, reliable biomarkers in neurological diseases are still lacking. Diffusional MRI, MR spectroscopy, and the assessment of regional atrophy are promising approaches, but they cannot be simultaneously used on a single patient. Thus, for further research progress, reliable animal models are needed. To this aim, we have used the clinical MRI to assess neurodegenerative processes in the hSOD-1(G93A) ALS rat model and in the trimethyltin (TMT)-treated model of Alzheimer's-like disease. T2-weighted (T2W) hyperintensive neurodegenerative foci were found in the brainstem of the ALS rat with apparent lateral ventricle dilation (T1W-hypointensity vs. T2W-hyperintensity). Degenerative processes in these areas were also confirmed by confocal images of GFAP-positive astrogliosis. MRI after i.v.i. of magnetic anti-CD4 antibodies indicated an accumulation of inflammatory cells near dilated ventricles. TMT-treated rats also revealed the dilation of lateral ventricles. Expected deterioration in the hippocampus was not observed by clinical MRI, but immunocytochemistry could reveal significant redistribution of macro- and microglia in this structure. In both models, Gd-DTPA contrast revealed a compromised blood brain barrier that may serve as the passage for inflammatory immune cells in the vicinity of dilated lateral ventricles. Moreover, in both models the midbrain region of the dorsal hippocampus was the target of BBB compromise, thus revealing a potentially vulnerable point that can be the primary target of neurodegeneration in the central nervous system., ((c) 2009 Wiley-Liss, Inc.)
- Published
- 2009
- Full Text
- View/download PDF
129. [Congenital tuberculosis in preterm neonate: a case report].
- Author
-
Bonnet C, Michel F, Nicaise C, Chaumoître K, Hassid S, Uters M, Thomachot L, Vialet R, Retornaz K, Lagier P, and Martin C
- Subjects
- Diagnosis, Differential, Drug Therapy, Combination, Feces microbiology, Female, Follow-Up Studies, Humans, Infant, Newborn, Infant, Premature, Treatment Outcome, Tuberculosis drug therapy, Antitubercular Agents therapeutic use, Mycobacterium tuberculosis isolation & purification, Tuberculosis congenital
- Abstract
Congenital tuberculosis is a rare but severe disease. Diagnosis is often delayed, especially in preterm neonates. We report a premature infant born after 27 weeks of gestation and in vitro fertilization. Tuberculosis was suspected after 112 days of life in view of sepsis, respiratory distress, and the discovery of maternal tuberculosis. Mycobacterium tuberculosis was isolated in endotracheal aspirates, gastric aspirates, and stools. The infant initially received four antitubercular antibiotics over 3 months, then two antibiotics over 9 months. A wide screening for a possible nosocomial transmission from this index case was set up. At the chronological age of 2 years, the baby is healthy without after-effects and no secondary cases were diagnosed. This article recalls the difficulty diagnosing congenital tuberculosis, particularly in preterm neonates. It also underlines the need to raise and eliminate the diagnosis of tuberculosis in an infertile woman.
- Published
- 2009
- Full Text
- View/download PDF
130. Aquaporin-4 overexpression in rat ALS model.
- Author
-
Nicaise C, Soyfoo MS, Authelet M, De Decker R, Bataveljic D, Delporte C, and Pochet R
- Subjects
- Amino Acid Substitution, Amyotrophic Lateral Sclerosis pathology, Animals, Animals, Genetically Modified, Astrocytes metabolism, Astrocytes pathology, Base Sequence, DNA Primers genetics, Disease Models, Animal, Humans, Immunohistochemistry, Microscopy, Fluorescence, Microscopy, Immunoelectron, Motor Neurons metabolism, Motor Neurons pathology, Mutagenesis, Site-Directed, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Recombinant Proteins genetics, Recombinant Proteins metabolism, Spinal Cord blood supply, Spinal Cord pathology, Superoxide Dismutase genetics, Superoxide Dismutase metabolism, Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis genetics, Amyotrophic Lateral Sclerosis metabolism, Aquaporin 4 genetics, Aquaporin 4 metabolism, Spinal Cord metabolism
- Abstract
Onset of motoneuron death characterizing amyotrophic lateral sclerosis (ALS) is closely linked to modified astrocytic and glial environments. Here, we show that in the spinal cord from transgenic rat overexpressing mutated human SOD1, aquaporin-4 mRNA and protein are specifically overexpressed in the gray matter at end stage of disease. Immunohistochemistry and double immunofluorescence allowed to detect, in the spinal cord gray matter of the ALS rat, increased aquaporin-4 surrounding both vessel and motoneuron perikarya. The use of pre-embedding immunohistochemistry at electron microscopic level confirmed such localization associated with swollen astrocytic processes surrounding the vessels. The AQP4 immunohistochemical labeling surrounding several motoneuron perikarya was only seen in ALS rats. Identification of this AQP4-positive cellular type remains unclear., ((c) 2008 Wiley-Liss, Inc.)
- Published
- 2009
- Full Text
- View/download PDF
131. Live monitoring of brain damage in the rat model of amyotrophic lateral sclerosis.
- Author
-
Bataveljić D, Djogo N, Zupunski L, Bajić A, Nicaise C, Pochet R, Bacić G, and Andjus PR
- Subjects
- Amyotrophic Lateral Sclerosis pathology, Animals, Brain Diseases complications, Disease Models, Animal, Disease Progression, Humans, Magnetic Resonance Imaging, Microscopy, Confocal, Rats, Rats, Sprague-Dawley, Amyotrophic Lateral Sclerosis complications, Brain Diseases diagnosis, Brain Diseases pathology, Tissue Survival
- Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder affecting upper and lower motoneurons. The transgenic ALS rat model (hSOD-1(G93A)) was used for magnetic resonance imaging (MRI) study using a low field wide bore magnet. T2-weighted hyperintensities were observed in the brainstem, rubrospinal tract and vagus motor nuclei with prominent lateral ventricle and cerebral aqueduct enlargements. These changes could be observed already in presymptomatic animals. T2*-weighted MRI with magnetically labeled antibodies (against CD4) revealed lymphocyte infiltration in the brainstem-midbrain region corresponding to the areas of dilated lateral ventricles. Confocal imaging revealed reactive astroglia in these areas. Thus, with the use of wide bore MRI new sites of neurodegeneration and inflammation were revealed in the hSOD-1(G93A) rat model.
- Published
- 2009
132. Transient potent BCR-ABL inhibition is sufficient to commit chronic myeloid leukemia cells irreversibly to apoptosis.
- Author
-
Shah NP, Kasap C, Weier C, Balbas M, Nicoll JM, Bleickardt E, Nicaise C, and Sawyers CL
- Subjects
- Antineoplastic Agents pharmacology, Benzamides, Cell Line, Tumor, Cell Survival, Dasatinib, ErbB Receptors antagonists & inhibitors, ErbB Receptors metabolism, Humans, Imatinib Mesylate, K562 Cells, Kinetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism, Piperazines pharmacology, Protein Kinase Inhibitors pharmacology, Pyrimidines pharmacology, Thiazoles pharmacology, Apoptosis, Fusion Proteins, bcr-abl antagonists & inhibitors, Fusion Proteins, bcr-abl physiology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology
- Abstract
The BCR-ABL inhibitor dasatinib achieves clinical remissions in chronic myeloid leukemia (CML) patients using a dosing schedule that achieves potent but transient BCR-ABL inhibition. In vitro, transient potent BCR-ABL inhibition with either dasatinib or imatinib is cytotoxic to CML cell lines, as is transient potent EGFR inhibition with erlotinib in a lung cancer cell line. Cytotoxicity correlates with the magnitude as well as the duration of kinase inhibition. Moreover, cytotoxicity with transient potent target inhibition is equivalent to prolonged target inhibition and in both cases is associated with BIM activation and rescued by BCL-2 overexpression. In CML patients receiving dasatinib once daily, response correlates with the magnitude of BCR-ABL kinase inhibition, thereby demonstrating the potential clinical utility of intermittent potent kinase inhibitor therapy.
- Published
- 2008
- Full Text
- View/download PDF
133. Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents.
- Author
-
Nicaise C, Prozzi D, Viaene E, Moreno C, Gustot T, Quertinmont E, Demetter P, Suain V, Goffin P, Devière J, and Hols P
- Subjects
- Acute Disease, Alanine metabolism, Ammonia metabolism, Animals, Carbon Tetrachloride, Chronic Disease, Disease Models, Animal, Hyperammonemia etiology, Hyperammonemia metabolism, Lactobacillus plantarum genetics, Lactulose pharmacology, Liver Failure chemically induced, Liver Failure complications, Liver Failure diet therapy, Male, Mice, Mice, Inbred C57BL, Probiotics administration & dosage, Rats, Rats, Inbred Lew, Thioacetamide, Hyperammonemia therapy, Lactobacillus plantarum metabolism, Probiotics therapeutic use
- Abstract
Unlabelled: Hyperammonemia is a common complication of acute and chronic liver diseases. Often accompanied with side effects, therapeutic interventions such as antibiotics or lactulose are generally targeted to decrease the intestinal production and absorption of ammonia. In this study, we aimed to modulate hyperammonemia in three rodent models by administration of wild-type Lactobacillus plantarum, a genetically engineered ammonia hyperconsuming strain, and a strain deficient for the ammonia transporter. Wild-type and metabolically engineered L. plantarum strains were administered in ornithine transcarbamoylase-deficient Sparse-fur mice, a model of constitutive hyperammonemia, in a carbon tetrachloride rat model of chronic liver insufficiency and in a thioacetamide-induced acute liver failure mice model. Constitutive hyperammonemia in Sparse-fur mice and hyperammonemia in a rat model of chronic hepatic insufficiency were efficiently decreased by Lactobacillus administration. In a murine thioacetamide-induced model of acute liver failure, administration of probiotics significantly increased survival and decreased blood and fecal ammonia. The ammonia hyperconsuming strain exhibited a beneficial effect at a lower dose than its wild-type counterpart. Improved survival in the acute liver failure mice model was associated with lower blood ammonia levels but also with a decrease of astrocyte swelling in the brain cortex. Modulation of ammonia was abolished after administration of the strain deficient in the ammonium transporter. Intestinal pH was clearly lowered for all strains and no changes in gut flora were observed., Conclusion: Hyperammonemia in constitutive model or after acute or chronic induced liver failure can be controlled by the administration of L. plantarum with a significant effect on survival. The mechanism involved in this ammonia decrease implicates direct ammonia consumption in the gut.
- Published
- 2008
- Full Text
- View/download PDF
134. Gemals, a new drug candidate, extends lifespan and improves electromyographic parameters in a rat model of amyotrophic lateral sclerosis.
- Author
-
Nicaise C, Coupier J, Dabadie MP, De Decker R, Mangas A, Bodet D, Poncelet L, Geffard M, and Pochet R
- Subjects
- Animals, Animals, Genetically Modified, Dose-Response Relationship, Drug, Drug Combinations, Polylysine administration & dosage, Rats genetics, Rats, Sprague-Dawley, Treatment Outcome, Amyotrophic Lateral Sclerosis drug therapy, Amyotrophic Lateral Sclerosis physiopathology, Disease Models, Animal, Electromyography drug effects, Longevity drug effects, Muscle Contraction drug effects, Polylysine analogs & derivatives, Weight Loss drug effects
- Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal disease involving selective and progressive degeneration and death of motor neurons. ALS is a multifactorial disease in which oxidative stress, glutamate excitotoxicity, intracellular aggregates, neurofilamentous disorganization, zinc excitotoxicity, mitochondrial damage, neuroinflammation, abnormalities in growth factors and apoptosis play a role. Any therapeutic approach to delay or stop the evolution of ALS should therefore ideally target these multiple pathways leading to motor neuron death. We have developed a combination therapy (Gemals) composed of functional polypeptides (fatty acids, free radical scavengers and amino acids linked to poly-L-lysine), chosen according to their known potentiality for regeneration or protection of neuronal components such as myelin, axon transport and mitochondria. We found that Gemals significantly extended lifespan and improved electromyographic parameters in a SOD1(G93A) rat model. The use of two drug concentrations indicated a possible dose dependence. These initial findings open the way to further investigation necessary to validate this new drug as a candidate for ALS treatment.
- Published
- 2008
- Full Text
- View/download PDF
135. Randomized controlled trial of sevoflurane for intubation in neonates.
- Author
-
Hassid S, Nicaise C, Michel F, Vialet R, Thomachot L, Lagier P, and Martin C
- Subjects
- Blood Gas Analysis statistics & numerical data, Humans, Infant, Newborn, Infant, Premature, Intensive Care Units, Neonatal, Monitoring, Physiologic, Sevoflurane, Hypnotics and Sedatives administration & dosage, Intubation, Intratracheal, Methyl Ethers administration & dosage, Preanesthetic Medication methods
- Abstract
Background: Our aim was to determine whether sevoflurane can be used with safety and efficacy for anesthesia during intubation in term and preterm neonates in a prospective randomized-controlled nonblinded study in a tertiary neonatal intensive care unit., Methods: Thirty-three neonates were randomly allocated to receive sevoflurane (inspired concentrations varying from 2% to 5%) or no medication (preoxygenation with 100% oxygen alone) before intubation. Minute by minute heart rate (HR), mean arterial blood pressure, SpO(2) and number of episodes of bradycardia (HR < 100 b.min(-1)) and desaturation (SpO(2) < 85% for >30 s) were noted from 5 min before to 10 min after intubation. Operator experience, ease and number of attempts were noted., Results: No major adverse events were noted in the study group compared with the control group [hypotension (37.5% vs 37.5%, NS), number of desaturations [37.5% vs 44.5%, NS)]. Hypertension (25%, vs 56.3%P = 0.04) and incidence of bradycardias (8.3% vs 44.4%, P < 0.01) were greater in the control group. Intubation was easier in the study group: no movements: 95.5% vs 28% (P < 0.005); good glottis visualization: 73% vs 33% (P = 0.013). The failure rate was lower in the study group (25% vs 39%), but this difference was not statistically significant., Conclusion: Anesthesia for intubation with sevoflurane in neonates is well tolerated, even in the less mature. It facilitates the conditions for intubation and leads to fewer adverse events. Other studies are necessary to confirm these preliminary results.
- Published
- 2007
- Full Text
- View/download PDF
136. Continuous low-dose infusion of terlipressin as a rescue therapy in meningococcal septic shock.
- Author
-
Michel F, Thomachot L, David M, Nicaise C, Vialet R, Di Marco JN, Lagier P, and Martin C
- Subjects
- Child, Preschool, Female, Humans, Infusions, Parenteral, Lypressin administration & dosage, Terlipressin, Lypressin analogs & derivatives, Meningococcal Infections drug therapy, Neisseria meningitidis, Serogroup B, Shock, Septic drug therapy, Vasoconstrictor Agents administration & dosage
- Published
- 2007
- Full Text
- View/download PDF
137. [Transcutaneous bilirubin measurement in preterm infants].
- Author
-
Mercanti I, Michel F, Thomachot L, Loundou DA, Nicaise C, Vialet R, Di Marco JN, Lagier P, and Martin C
- Subjects
- Blood Chemical Analysis methods, Female, Humans, Infant, Newborn, Male, Prospective Studies, Reproducibility of Results, Bilirubin blood, Hyperbilirubinemia diagnosis, Infant, Premature
- Abstract
Unlabelled: Transcutaneous bilirubinometry is an effective screening tool for neonatal jaundice in full-term babies. But its accuracy is not shown yet in preterm infants., Methodology: We carried out a prospective study in a neonatal intensive care unit. The study included 47 preterm infants. From birth, a transcutaneous bilirubin measurement (BTc) using the BiliCheck was made on the forehead of each newborn every 8 h. Blood sampling for determination of total serum bilirubin (BS) was combined with BTc: 1) if value of BTc was higher than limits values for phototherapy; 2) on the second day of life and 3) 4 hours after cessation of phototherapy., Results: Mean gestational age was 30 week and mean birth weight was 1419 g. We studied 151 pairs of BTc and BS. Mean values obtained by BTc and BS were respectively 160.6+/-50 mumol/L and 190.6+/-61.4 mumol/L. A significant correlation between BTc and BS was found. But the limits of agreement were very wide. The negative predictive value (NPV) of BTc was above 90% in each group of gestational age., Discussion: The need for phototherapy cannot be determined by BTc in preterm infants. But the BTc is reliable when its value is under the limits for phototherapy., Conclusion: With a very high incidence of neonatal jaundice (87%) in our cohort, a value of BTc under the limits for phototherapy has a good NPV in preterm infants.
- Published
- 2007
- Full Text
- View/download PDF
138. Osteosarcoma cell-calcium signaling through tissue factor-factor VIIa complex and factor Xa.
- Author
-
Daubie V, De Decker R, Nicaise C, and Pochet R
- Subjects
- Alternative Splicing, Calcium metabolism, Cell Line, Cell Line, Tumor, Cell Survival drug effects, Gene Expression, Humans, Immunohistochemistry, Osteosarcoma genetics, Osteosarcoma metabolism, Osteosarcoma pathology, Peptide Fragments metabolism, Reverse Transcriptase Polymerase Chain Reaction, Thromboplastin genetics, Thromboplastin metabolism, Time Factors, Calcium Signaling drug effects, Factor VIIa pharmacology, Factor Xa pharmacology, Thromboplastin pharmacology
- Abstract
The cells responsible for bone formation express protease-activated receptors. Although serine protease thrombin has been shown to elicit functional responses in bone cells that impact on cell survival and alkaline phosphatase activity, nothing is known about tissue factor, factor VIIa, and factor Xa, the serine proteases that act upstream of thrombin in the coagulation cascade. This paper demonstrates that tissue factor is expressed in the osteoblast-like cell line SaOS-2 and, that tissue factor in a factor VIIa-bound complex induces a transient intracellular Ca(2+) increase through protease-activated receptor-2. In SaOS-2 cells, factor Xa induced a sustained intracellular Ca(2+) response, as does SLIGRL, a PAR2-activating peptide, and PAR-1-dependent cell viability.
- Published
- 2007
- Full Text
- View/download PDF
139. Airway humidification with a heat and moisture exchanger in mechanically ventilated neonates : a preliminary evaluation.
- Author
-
Fassassi M, Michel F, Thomachot L, Nicaise C, Vialet R, Jammes Y, Lagier P, and Martin C
- Subjects
- Hot Temperature, Humans, Humidity, Incubators, Infant, Infant, Infant, Newborn, Intensive Care Units, Neonatal, Respiration, Artificial instrumentation, Respiratory Distress Syndrome, Newborn therapy
- Abstract
Objective: We set out to evaluate the efficacy of passive inspiratory gas conditioning in mechanically ventilated neonates and compared it with that of a heated humidifier (HH)., Design: Prospective, randomized, controlled study., Setting: Neonatal and pediatric intensive care unit., Patients: Fourteen mechanically ventilated neonates nursed in incubators., Interventions: The HH was set to deliver a temperature of 37 degrees C and an absolute humidity of 40 mgH(2)O/l at the incubator entrance. Inspired temperature (T degrees ) and absolute humidity (AH) were measured by the psychometric method, transpulmonary pressure (Tpres) by means of a differential pressure transducer. Measurements were performed at 5, 10, and 15 min., Measurements and Results: The values of T degrees were significantly higher using the HH (34.6+/-1.6 degrees C) than the heat and moisture exchanger (HME) (33.8+/2.3, p<0.001). The values of AH were significantly higher using the HH (36.6+/-2.5 mgH(2)O/l) than the HME (32.4+/-2.8 mgH(2)O/l, p<0.001). No significant changes were observed in transpulmonary pressure. A significant positive correlation was observed between incubator temperature and the temperature delivered by the HH (R(2)=0.61, p<0.001)., Conclusions: The use of HMEs in neonates made it possible to achieve an absolute humidity of 28 mgH(2)O/l or more and a temperature of 30 degrees C or more. Higher values are obtained using a HH.
- Published
- 2007
- Full Text
- View/download PDF
140. Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failure.
- Author
-
Quintas-Cardama A, Kantarjian H, Jones D, Nicaise C, O'Brien S, Giles F, Talpaz M, and Cortes J
- Subjects
- Adult, Aged, Benzamides, Cytogenetic Analysis, Dasatinib, Drug Resistance, Neoplasm, Follow-Up Studies, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Middle Aged, Piperazines therapeutic use, Pyrimidines adverse effects, Pyrimidines therapeutic use, Thiazoles adverse effects, Treatment Outcome, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Pyrimidines administration & dosage, Thiazoles administration & dosage
- Abstract
Developing strategies to counteract imatinib resistance constitutes a challenge in chronic myelogenous leukemia (CML). Therapy with the tyrosine kinase inhibitors nilotinib (AMN107) and dasatinib (BMS-354825) has produced high rates of hematologic and cytogenetic response. Src kinase activation has been linked to Bcr-Abl-mediated leukemogenesis and CML progression. In addition to binding Abl kinase with less stringent conformational requirements than imatinib, dasatinib is a potent Src kinase inhibitor. In the current study, we report on 23 patients with CML (19 of them in accelerated or blastic phases) treated with dasatinib after treatment failure with both imatinib and nilotinib. More than half (13; 57%) of 23 patients responded to dasatinib: 10 (43%) had a complete hematologic response (CHR), including 7 (30%) who had a cytogenetic response (2 complete, 4 partial, and 1 minor). These results suggest that dasatinib may be active in some patients after failure with both imatinib and nilotinib.
- Published
- 2007
- Full Text
- View/download PDF
141. Chemokine receptor CCR5 deficiency exacerbates cerulein-induced acute pancreatitis in mice.
- Author
-
Moreno C, Nicaise C, Gustot T, Quertinmont E, Nagy N, Parmentier M, Louis H, and Devière J
- Subjects
- Acute Disease, Animals, Female, Mice, Mice, Knockout, Pancreatitis chemically induced, Receptors, CCR5 deficiency, Receptors, CCR5 genetics, Ceruletide, Pancreatitis metabolism, Pancreatitis pathology, Receptors, CCR5 metabolism
- Abstract
Acute pancreatitis (AP) is an inflammatory disease involving the production of different cytokines and chemokines and is characterized by leukocyte infiltration. Because the chemokine receptor CCR5 and its ligands [the CC chemokines CCL3/MIP-1alpha, CCL4/MIP-1beta, and CCL5/regulated upon activation, normal T cell expressed and secreted (RANTES)] regulate leukocyte chemotaxis and activation, we investigated the expression of CCR5 ligands and the role of CCR5 and its ligands in experimental AP in mice. AP was induced by hourly intraperitoneal injections of cerulein in CCR5-deficient (CCR5(-/-)) or wild-type (WT) mice. Induction of AP by cerulein resulted in an early increase of pancreatic CCL2, CCL3, and CCL4 mRNA expression, whereas CCL5 mRNA expression occurred later. CCR5(-/-) mice developed a more severe pancreatic injury than WT mice during cerulein-induced AP, as assessed by a more pronounced increase in serum amylase and lipase levels and by more severe pancreatic edema, inflammatory infiltrates (mainly neutrophils), and necrosis. CCR5(-/-) mice also exhibited increased production of CCL2/MCP-1, CCL3/MIP-1alpha, and CCL4/MIP-1beta during the course of cerulein-induced AP. In vivo simultaneous neutralization of CC chemokines with monoclonal antibodies in CCR5(-/-) mice reduced the severity of cerulein-induced AP, indicating a role of CC chemokines in exacerbating the course of AP in the absence of CCR5. Moreover, simultaneous neutralization of CCR5 ligands in WT mice also reduced the severity of cerulein-induced AP. In conclusion, lack of the chemokine receptor CCR5 exacerbates experimental cerulein-induced AP and leads to increased levels of CC chemokines and a more pronounced pancreatic inflammatory infiltrate, suggesting that CCR5 expression can modulate severity of AP.
- Published
- 2006
- Full Text
- View/download PDF
142. Differential liver sensitization to toll-like receptor pathways in mice with alcoholic fatty liver.
- Author
-
Gustot T, Lemmers A, Moreno C, Nagy N, Quertinmont E, Nicaise C, Franchimont D, Louis H, Devière J, and Le Moine O
- Subjects
- Animals, Ethanol pharmacology, Fatty Liver, Alcoholic metabolism, Female, Liver metabolism, Mice, Mice, Inbred C57BL, NADP physiology, Oxidation-Reduction, RNA, Messenger biosynthesis, Toll-Like Receptors biosynthesis, Toll-Like Receptors genetics, Fatty Liver, Alcoholic immunology, Signal Transduction physiology, Toll-Like Receptors physiology
- Abstract
Gut-derived, endotoxin-mediated hepatocellular damage has been postulated to play a crucial role in the pathogenesis of alcohol-induced liver injury in rodents. Endotoxins induce production of tumor necrosis factor alpha (TNF-alpha) by Kupffer cells via Toll-like receptor (TLR) 4 and contribute to liver injury. This study addressed the contribution of other TLRs and ligands to alcoholic fatty liver. C57Bl6/J mice were fed a modified Lieber-DeCarli diet. Serum aminotransferase measurements, histological analysis, and quantification of liver TNF-alpha and TLR1-9 messenger RNA (mRNA) were performed. The effect of TLR ligands on liver injury was assessed in vivo. Neomycin and metronidazole or diphenyleneiodonium sulfate (DPI) were administered to evaluate the role of gut bacteria and NADPH oxidase activity, respectively, in hepatic TLR expression. Enteral ethanol (EtOH) exposure induced steatosis and increased liver weight, aminotransferase levels, and expression of TLR1, 2, 4, 6, 7, 8, and 9 liver mRNA. Injection of lipoteichoic acid, peptidoglycan (PGN), lipopolysaccharide (LPS), loxoribine, and oligonudeotide containing CpG (ISS-ODN) increased TNF-alpha mRNA expression more in the livers of EtOH-fed mice than in control mice. PGN, LPS, flagellin, and ISS-ODN induced liver inflammatory infiltrate in EtOH-fed mice but not control mice. Addition of antibiotics reduced the severity of alcoholic fatty liver without affecting TLR expression, whereas daily DPI injections reduced the EtOH-mediated upregulation of TLR2, 4, 6, and 9 mRNA. In conclusion, EtOH-fed mice exhibited an oxidative stress dependent on upregulation of multiple TLRs in the liver and are sensitive to liver inflammation induced by multiple bacterial products recognized by TLRs.
- Published
- 2006
- Full Text
- View/download PDF
143. CCR5 deficiency exacerbates T-cell-mediated hepatitis in mice.
- Author
-
Moreno C, Gustot T, Nicaise C, Quertinmont E, Nagy N, Parmentier M, Le Moine O, Devière J, and Louis H
- Subjects
- Animals, Chemical and Drug Induced Liver Injury pathology, Chemokine CCL3, Chemokine CCL4, Chemokines, CC metabolism, Concanavalin A, Female, Interferon-gamma metabolism, Interleukin-4 metabolism, Ligands, Liver immunology, Liver pathology, Macrophage Inflammatory Proteins metabolism, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Receptors, CCR5 immunology, Receptors, CCR5 metabolism, Severity of Illness Index, T-Lymphocytes metabolism, Tumor Necrosis Factor-alpha metabolism, Chemical and Drug Induced Liver Injury genetics, Chemical and Drug Induced Liver Injury immunology, Receptors, CCR5 genetics, T-Lymphocytes immunology
- Abstract
Experimental T-cell-mediated hepatitis induced by concanavalin A (Con A) involves the production of different cytokines and chemokines and is characterized by leukocyte infiltration. Because the chemokine receptor CCR5 and its ligands (CCL3, CCL4, and CCL5) regulate leukocyte chemotaxis and activation, we investigated the role of CCR5 during Con A-induced liver injury. Serum levels of CCR5 ligands and their hepatic transcript levels were significantly increased after Con A injection, whereas CCR5+ liver mononuclear cells were recruited to the liver. CCR5-deficient (CCR5-/-) mice disclosed increased mortality and liver injury following Con A administration compared with wild-type mice. CCR5-/- mice also exhibited increased production of interleukin 4, tumor necrosis factor alpha, CCL3, CCL4, and CCL5, and a prominent liver mononuclear cell infiltrate, among which many cells were CCR1+. In vivo neutralization of CCR5 ligands in CCR5-/- mice afforded a protection against hepatitis only when CCL5 was neutralized. In conclusion, CCR5 deficiency exacerbates T-cell-mediated hepatitis, and leads to increased levels of CCR5 ligands and a more pronounced liver mononuclear infiltrate, suggesting that CCR5 expression can modulate severity of immuno-mediated liver injury.
- Published
- 2005
- Full Text
- View/download PDF
144. Induction of FOXP3-expressing regulatory CD4pos T cells by human mature autologous dendritic cells.
- Author
-
Verhasselt V, Vosters O, Beuneu C, Nicaise C, Stordeur P, and Goldman M
- Subjects
- Antigen Presentation, CD4-Positive T-Lymphocytes drug effects, Coculture Techniques, Cytokines antagonists & inhibitors, Cytokines biosynthesis, DNA-Binding Proteins genetics, Forkhead Transcription Factors, Growth Substances pharmacology, Histocompatibility Antigens Class II physiology, Humans, Immune Tolerance, Lipopolysaccharides pharmacology, Lymphocyte Culture Test, Mixed, Phenotype, RNA, Messenger metabolism, Receptors, Interleukin-2 analysis, T-Lymphocyte Subsets immunology, CD4-Positive T-Lymphocytes immunology, DNA-Binding Proteins biosynthesis, Dendritic Cells immunology, Lymphocyte Activation
- Abstract
Current literature suggests that T cells recognizing antigen on mature dendritic cells (DC) differentiate into effector T cells whereas tolerance is induced when antigen is presented by immature DC. We investigated the consequences of the interactions between immature or lipopolysaccharide-matured DC and CD4(pos) T lymphocytes in absence of foreign antigen. While immature DC did not induce significant CD4(pos) T cell activation, we observed that a significant fraction of CD4(pos) T cells cultured with mature autologous DC displayed phenotypic features of activation and produced IL-2, IFN-gamma, IL-10 and TGF-beta. Furthermore, CD4(pos) T lymphocytes primed by mature, but not immature, autologous DC acquired regulatory properties. Indeed, when added to an allogeneic mixed leukocyte reaction, they suppressed the response of alloreactive T lymphocytes to the priming DC while responses to third-party stimulators were spared. The generation of CD4(pos) T cells with regulatory function by autologous stimulation did not require the presence of natural CD4(pos)CD25(pos) regulatory T cells. In addition, the acquisition of regulatory function by CD4(pos)CD25(neg) T cells stimulated by autologous mature DC was accompanied by the induction of FOXP3 expression. Our data suggest that during inflammatory conditions, presentation of self antigens by mature DC to autologous T lymphocytes could contribute to the generation of regulatory mechanisms.
- Published
- 2004
- Full Text
- View/download PDF
145. [Neonatal consequences of preterm premature rupture of membrane (PPROM) at 24-34 WG: 118 singleton pregnancies].
- Author
-
Nicaise C, Gire C, Fagianelli P, Debriere R, Thomachot L, d'Ercole C, and Boubli L
- Subjects
- Brain Diseases diagnosis, Brain Diseases etiology, Brain Diseases mortality, Bronchopulmonary Dysplasia diagnosis, Bronchopulmonary Dysplasia etiology, Bronchopulmonary Dysplasia mortality, Chorioamnionitis diagnosis, Chorioamnionitis etiology, Female, Fetal Membranes, Premature Rupture complications, France epidemiology, Humans, Infant Mortality, Infant, Newborn, Infant, Premature, Pregnancy, Pregnancy Trimester, Third, Prospective Studies, Sepsis diagnosis, Sepsis etiology, Fetal Membranes, Premature Rupture diagnosis
- Abstract
Objectives: To evaluate the outcome of preterm infants born after preterm premature rupture of membranes (PPROM) between 24 and 34 weeks gestation (WG)., Methods: One hundred and eighteen consecutive singleton infants were included in a prospective unicenter study during 3 years. A PPROM management had been instituted by the local obstetrician's board committee. In case of suspected chorioamniotitis defined by maternal or fetal criteria or in case of fetal heart rate abnormalities, a fetal extraction was decided. Diagnosis of chorioamnionitis was confirmed regarding the results of placenta culture and/or histology. Neonatal sepsis was defined by positive blood placenta culture or by the association of 2 positive bacterial cultures with a CRP>15 mg/l., Results: The mean gestational age was 29.8 WG (24-34 SA) for PPROM and 30.4 WG for delivery. Mean latency period between PPROM and delivery was 119 hours +/- 208. The incidence of choriamnionitis was 31%. The overall incidence of neonatal sepsis was 15%. Neonatal mortality was 11.7%. Bronchopulmonary dysplasia occured in 8.4% of the liveborn cases and cranial ultrasound abnormalities (HIV III-IV, kystic LPV) in 11.7% of overall cases. Cerebral lesions were positively correlated with hypotension and negatively correlated with GA. Cerebral lesions seemed to occur more frequently in case of chorioamnionitis but it is not significant., Conclusion: In this study, in case of PPROM between 24-34 SA, gestational age and hypotension are correlated with neurologic injury.
- Published
- 2002
146. Clinical features and neuroradiological findings of mitochondrial pathology in six neonates.
- Author
-
Gire C, Girard N, Nicaise C, Einaudi MA, Montfort MF, and Dejode JM
- Subjects
- Female, Humans, Infant, Newborn, Magnetic Resonance Imaging, Male, Mitochondria enzymology, Mitochondria pathology, Mitochondrial Diseases enzymology, Mitochondrial Diseases pathology, Multienzyme Complexes metabolism, Muscle, Skeletal enzymology, Muscle, Skeletal ultrastructure, Brain pathology, Mitochondrial Diseases diagnosis
- Abstract
Objects: We hoped to itemize the clinical and neuroradiological features of six neonates with mitochondrial disorders., Methods: We examined a case series of six neonates. The diagnosis of mitochondrial cytopathy was made on the basis of spectrophotometric measurements of respiratory chain enzyme activities in skeletal muscle biopsy specimens. Magnetic resonance (MR) imaging was performed in all cases., Conclusions: The antenatal onset in five cases and the lack of any symptom-free interval are suggestive of fetal expression of the disease. No specific symptoms were found: arthrogryposis congenita multiplex in one, progressive hepatocellular dysfunction in three, encephalomyelopathy and cardiomyopathy in four. Complex I deficiency was found in three patients, while one patients had a defect of complex IV and the last a combined defect of complexes I and IV. Neuroradiological findings were either cerebral atrophy or white matter abnormalities of the brain stem in all cases but one and gave additional information, because clinical symptoms are not quite specific. The combination of clinical and MRI findings in neonatal cases can rule out hypoxic ischemic encephalopathy, which suggests an additional screening method to look for mitochondrial disorder.
- Published
- 2002
- Full Text
- View/download PDF
147. [Early cerebral MRI in preterm infants: correlations with EEG and outcome].
- Author
-
Le Menestrel-André S, Gire C, Roussel M, Girard N, Nicaise C, Tomachot L, Palix C, and Farnarier G
- Subjects
- Female, Humans, Infant, Newborn, Male, Prognosis, Retrospective Studies, Severity of Illness Index, Brain Diseases pathology, Brain Diseases physiopathology, Electroencephalography, Infant, Premature, Diseases pathology, Infant, Premature, Diseases physiopathology, Magnetic Resonance Imaging
- Abstract
Aim of the Study: Assess the potential benefits of performing an early cerebral MRI to evaluate the gravity of cerebral lesions among premature neonates at risk of neurologic sequels and establish correlations between EEG findings, abnormal neuroimaging findings and neurodevelopment., Methods: A MRI was performed in 34 premature newborn babies with abnormal neurological clinical signs, and/or with two abnormal EEG and/or with two abnormal cerebral ultrasound scans. The mean age and the adjusted age of our population were 5 weeks (range 1-11 weeks) and 35 weeks of adjusted age (range 29-40 weeks) respectively. The neuroimaging findings were correlated to the results of three EEGs (recorded before 15 days old, between 15 days and one month old, and after the first month of life) and to neurodevelopment., Results: Two statically significant correlations were found between: 1) the severity of brain injuries observed in MRI and the results of the latest EEG (sensitivity 100%, specificity 60%), 2) the severity of brain injuries observed in MRI and abnormal neurodevelopment (sensitivity 75%, specificity 80%). There was no correlation between the abnormal development and the results of EEG recordings., Conclusion: Early cerebral MRI is justified in a selected premature population. It is useful for the diagnosis, the evaluation of the severity of brain injury and for the management of these children. The correlation with EEGs traces allows the detection of the majority of prematures babies that will develop sequels.
- Published
- 2002
- Full Text
- View/download PDF
148. Preterm premature rupture of membrane and twin-to-twin transfusion syndrome before 20 weeks: a favourable outcome.
- Author
-
Gire C, Nicaise C, ShoJaï R, Chau C, Boubli L, and d'Ercole C
- Subjects
- Adult, Female, Humans, Infant, Newborn, Pregnancy, Pregnancy Outcome, Fetal Membranes, Premature Rupture diagnostic imaging, Fetofetal Transfusion diagnostic imaging, Ultrasonography, Prenatal
- Abstract
We describe a monochorionic twin gestation with a severe twin-to-twin transfusion syndrome associated with a preterm premature rupture of membranes at 20 weeks of gestation in the polyhydramniotic sac. The pregnancy was managed expectantly and outcome was favourable for the 2 neonates. We discuss how these two severe pathologies seem to counteract each other by compensations of their symptoms., (Copyright 2002 S. Karger AG, Basel)
- Published
- 2002
- Full Text
- View/download PDF
149. Ultrasonographic evaluation of cervical length in pregnancies complicated by preterm premature rupture of membranes.
- Author
-
Gire C, Faggianelli P, Nicaise C, Shojai R, Fiori A, Chau C, Boubli L, and D'Ercole C
- Subjects
- Adult, Chorioamnionitis epidemiology, Female, Humans, Obstetric Labor, Premature epidemiology, Predictive Value of Tests, Pregnancy, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, Cervix Uteri diagnostic imaging, Fetal Membranes, Premature Rupture diagnostic imaging, Ultrasonography, Prenatal
- Abstract
Objective: To evaluate the usefulness of transvaginal ultrasonography in the determination of the risk of preterm delivery and chorioamnionitis in pregnancies affected by preterm premature rupture of membranes preterm premature rupture of membranes., Design: One hundred and one singleton pregnancies with preterm premature rupture of membranes were included in this prospective study over a 3-year period. Patients underwent cervical length measurement by transvaginal ultrasonography at admission and thereafter, in the absence of chorioamnionitis, were managed expectantly., Results: The median time interval between admission and delivery (latency period) was 48 h. A cervical length of less than 20 mm was associated with a significant risk of early delivery (mean latency period was 59.44 +/- 159.93 h vs. 240.94 +/- 364.67; P < 0.05). There was no relation between cervical length and occurrence of chorioamnionitis or neonatal sepsis., Conclusions: These data suggest that the use of transvaginal ultrasonography for cervical length measurement during preterm premature rupture of membranes may predict an early delivery but cannot anticipate the risk of chorioamnionitis or neonatal sepsis.
- Published
- 2002
- Full Text
- View/download PDF
150. Erythropoietin as treatment for late hyporegenerative anemia in neonates with Rh hemolytic disease after in utero exchange transfusion.
- Author
-
Nicaise C, Gire C, Casha P, d'Ercole C, Chau C, and Palix C
- Subjects
- Humans, Infant, Newborn, Male, Anemia, Aplastic complications, Anemia, Aplastic drug therapy, Blood Transfusion, Intrauterine, Erythropoietin therapeutic use, Exchange Transfusion, Whole Blood, Recombinant Proteins therapeutic use, Rh Isoimmunization complications, Rh Isoimmunization therapy
- Abstract
We report the effects of recombinant human erythropoietin (rHuEPO) in the treatment of late hyporegenerative anemia in 2 neonates with Rh hemolytic disease who had received several in utero exchange transfusions. In both cases anemia occurred at 6 weeks of age and we started therapy at approximately 70 days of age. We used rHuEPO at 250 U/kg three times a week. We also used high-dose intravenous immunoglobulin therapy. One week after initiation of erythropoietin treatment, an increase in reticulocyte count and Hb level was noted in our 2 patients. They did not require further erythrocyte transfusions but they already had received two transfusions after birth. There were no side effects attributable to rHuEPO treatment., (Copyright 2002 S. Karger AG, Basel)
- Published
- 2002
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.