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1.
Arch Pediatr ; 28(1): 64-68, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33162325

ABSTRACT

OBJECTIVES: This study assessed the association between findings of lung ultrasound (LUS) performed in the pediatric emergency department (PED) on infants with bronchiolitis and need for respiratory support. METHODS: An observational study was carried out in the PED during the epidemic seasons in two consecutive years. Infants diagnosed with bronchiolitis who fulfilled the inclusion criteria were evaluated. A group of six pediatricians performed LUS and classified lung findings into four groups: normal pattern (A), moderate interstitial pattern (B1), severe interstitial pattern (B2), and isolated consolidation (C). The relationship between LUS findings and need for respiratory support was explored. An expert sonographer, blinded to the results, reviewed the ultrasound studies to determine the interobserver reliability. RESULTS: A total of 200 infants were included (mean age 5.7 months±4.4 SD); 65 (32.5%) obtained moderate clinical scores, while 23 (11.5%) needed respiratory support at admission and 34 (17.0%) at 48h. The ultrasound findings in the PED were the following: A=89 (44.5%), B1=55 (27.5%), B2=34 (17%), and C=22 (11%). Age less than 6 weeks and moderate bronchiolitis were correlated with abnormal LUS (P<0.005). The severity of interstitial ultrasound pattern has some correlation with an increased need for respiratory support. The interobserver concordance was high (0.95, confidence interval: 0.92-0.98). CONCLUSION: LUS is a feasible tool that may help to confirm the clinical impression and assess the need for respiratory support in children with bronchiolitis, but further multicenter studies are needed.


Subject(s)
Bronchiolitis/diagnostic imaging , Clinical Decision-Making/methods , Emergency Service, Hospital , Lung/diagnostic imaging , Point-of-Care Systems , Respiratory Therapy/statistics & numerical data , Severity of Illness Index , Bronchiolitis/therapy , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Observer Variation , Single-Blind Method , Ultrasonography
2.
Front Psychol ; 11: 559819, 2020.
Article in English | MEDLINE | ID: mdl-33117227

ABSTRACT

This study examines the mental health outcomes among the healthcare personnel and the general population and the role of socioeconomic status. Eight hundred and eighty-four (884) residents in Nigeria comprising 382 healthcare personnel and 502 general residents aged between 18 to 78 years (M = 28.75, SD = 8.17) responded to an online survey with measures of Impact of Event Scale-Revised (IES-R), Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), and Insomnia Severity Index. Collected data were subjected to statistical analysis using the SPSS v.25. Results revealed significant difference in the prevalence of depressive symptoms (χ2 = 14.26; df = 4; p < 0.01), insomnia symptoms (χ2 = 40.21; df = 3; p < 0.01), posttraumatic stress symptoms (χ2 = 08.34; df = 3; p < 0.05), and clinical anxiety symptoms (χ2 = 06.71; df = 1; p < 0.05) among healthcare personnel and the general population, with a higher prevalence reported by the healthcare personnel. Further, socioeconomic status significantly influences prevalence of depressive symptoms (χ2 = 04.5; df = 4; p < 0.05). The study concluded that the prevalence of poor mental health outcomes during the COVID-19 crisis among Nigerians is worrisome. Also, the socioeconomic status of the citizens has serious implications on depressive symptoms. The study recommends that the government and stakeholders should pay attention to policy that will favor tele-mental health services and adequate palliative measures to cushion the psycho-economic impacts of COVID-19 on residents. Also, healthcare workers should be considered for better remuneration and other welfare benefits to sustain their well-being during the present and future pandemic.

3.
Soc Sci Humanit Open ; 2(1): 100052, 2020.
Article in English | MEDLINE | ID: mdl-34173493

ABSTRACT

This study examine the psychological distress experience of Nigerians during the COVID-19 pandemic, across gender. From March 20, 2020, to April 12, 2020, this descriptive survey used a snowballing sampling technique to select 502-Nigerians with an online semi-structured questionnaire detailing the impact of Event Scale-Revised, Generalized Anxiety Disorder - 7 item scale, Patient Health Questionnaire and Insomnia Severity Index. Gender had an insignificant difference in the level of insomnia (χ2 â€‹= â€‹04.93; df â€‹= â€‹3; p â€‹> â€‹0.05), however, 20.8% of males had sub-threshold of insomnia, 8.2% experienced moderate insomnia and 5.9% had severe insomnia; 32% females reported sub-threshold of insomnia, 12.4% had moderate insomnia while 3.6% had severe insomnia. Also, gender had an insignificant difference in the measures of depression (χ2 â€‹= â€‹01.94; df â€‹= â€‹4; p â€‹> â€‹0.05); 55.4% males reported minimal depression, 22.3% had mild depression, 11.9% had moderate depression; 6.7%-3.7% males had moderate to severe depression while, 49.3% of the females had minimal depression, 26.7% reported mild depression, 14.29% had moderate depression, 4.4%-5.3% had moderate to severe depressive symptoms. Posttraumatic Stress Symptoms (PTSS) has no gender difference among respondents (χ2 â€‹= â€‹02.51; df â€‹= â€‹3; p â€‹> â€‹0.05); 23% of males reported partial PTSS, 17.5% presented clinical PTSS, and 21.6% males had severe PTSS; while 29.3% of females had severe PTSS, 24% reported partial PTSS and 18.7% had clinical PTSS. Respondents reported insignificant gender differences on anxiety (χ2 â€‹= â€‹0.08; df â€‹= â€‹1; p â€‹> â€‹0.05), while 51% reported moderate anxiety and 49% exhibited severe anxiety during the COVID-19 pandemic in Nigeria. Findings revealed that Nigerians experienced psychological distress during COVID-19 pandemic. The government and stakeholders should initiate tele-mental health services to serve as alternative to traditional treatment to manage present and future pandemic psychological implications among Nigerians.

4.
Int J Breast Cancer ; 2019: 8536548, 2019.
Article in English | MEDLINE | ID: mdl-31355003

ABSTRACT

In Africa, breast cancer closely compares with cervical cancer as the most common malignancy affecting women and the incidence rates appear to be rising. Eritrea is experiencing a growing breast cancer problem, but little is presently known on tumor patterns, breast cancer epidemiology, and risk factors. The main objective of this study is to provide baseline data on breast cancer incidence in both sexes in Eritrea. This study was carried out retrospectively and quantitatively by collecting, abstracting, analyzing, coding, and interpreting data recorded in National Health Laboratory (NHL) using CanReg5 ver. 5.00.35. Extracting and classification of the tumor data was done using topography, morphology together with the ICD-10. To generate the incidence rate for the seven years the Eritrean population dataset was used from the population pyramid net for 2014. After we entered all the data from Pathology department in NHL, data was analyzed using the predetermined and developed built-in analysis tools of CanReg5 software and Microsoft Excel 2010. A total number of 9,403 pathology cases were recorded from 2011 to 2017. Out of these 1,497 cases were confirmed as cytology and histology of breast cases. From 1,497 confirmed breast cases in both sexes, the incidence of benign cases was higher than incidence of malignant cases with the case number of 1, 149, and 348, respectively. Out of the 1,497 cases, 1,447 (96.66%) were females; this included a total incidence cases of female benign and malignant breast cases 1,111 (76.78%), and 336 (23.22%), respectively. In both female and male age group the highest positive cases were found in the age greater than 85. The incidence age standard rate per 100,000 in females and male was 3.3 and 0.2, respectively. In sum, the age standardized incidence of breast cancer was relatively low. However, it is our opinion that the low prevalence may be due to low awareness and a highly centralized screening and diagnostic services. This limits access. Altogether, it is our opinion that breast cancer presents a burden to Eritrean ministry of health.

5.
Neuroimage Clin ; 20: 415-423, 2018.
Article in English | MEDLINE | ID: mdl-30128280

ABSTRACT

Background: Behavioral, cognitive and functional particularities in autism differ according to autism subgroups and might be associated with domain-specific cognitive strengths. It is unknown whether structural changes support this specialization. We investigated the link between cortical folding, its maturation and cognitive strengths in autism subgroups presenting verbal or visuo-spatial peaks of abilities. Methods: We measured gyrification, a structural index related to function, in 55 autistic participants with (AS-SOD, N = 27) or without (AS-NoSOD, N = 28) a speech onset delay (SOD) with similar symptom severity but respectively perceptual and verbal cognitive strengths, and 37 typical adolescents and young adults matched for intelligence and age. We calculated the local Gyrification Index (lGI) throughout an occipito-temporal region of interest and independently modeled age and peak of ability effects for each group. Results: Unique gyrification features in both autistic groups were detected in localized clusters. When comparing the three groups, gyrification was found lower in AS-SOD in a fusiform visual area, whereas it was higher in AS-NoSOD in a temporal language-related region. These particular areas presented age-related gyrification differences reflecting contrasting local maturation pathways in AS. As expected, peaks of ability were found in a verbal subtest for the AS-NoSOD group and in the Block Design IQ subtest for the AS-SOD group. Conclusions: Irrespective of their direction, regional gyrification differences in visual and language processing areas respectively reflect AS-SOD perceptual and AS-NoSOD language-oriented peaks. Unique regional maturation trajectories in the autistic brain may underline specific cognitive strengths, which are key variables for understanding heterogeneity in autism.


Subject(s)
Asperger Syndrome/diagnostic imaging , Autistic Disorder/diagnostic imaging , Cognition/physiology , Occipital Lobe/diagnostic imaging , Temporal Lobe/diagnostic imaging , Adolescent , Adult , Asperger Syndrome/psychology , Autistic Disorder/psychology , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/physiology , Female , Humans , Male , Occipital Lobe/physiology , Temporal Lobe/physiology , Young Adult
6.
J Psychiatr Res ; 68: 285-92, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26037888

ABSTRACT

A continuum of phenotypes makes up the autism spectrum (AS). In particular, individuals show large differences in language acquisition, ranging from precocious speech to severe speech onset delay. However, the neurological origin of this heterogeneity remains unknown. Here, we sought to determine whether AS individuals differing in speech acquisition show different cortical responses to auditory stimulation and morphometric brain differences. Whole-brain activity following exposure to non-social sounds was investigated. Individuals in the AS were classified according to the presence or absence of Speech Onset Delay (AS-SOD and AS-NoSOD, respectively) and were compared with IQ-matched typically developing individuals (TYP). AS-NoSOD participants displayed greater task-related activity than TYP in the inferior frontal gyrus and peri-auditory middle and superior temporal gyri, which are associated with language processing. Conversely, the AS-SOD group only showed enhanced activity in the vicinity of the auditory cortex. We detected no differences in brain structure between groups. This is the first study to demonstrate the existence of differences in functional brain activity between AS individuals divided according to their pattern of speech development. These findings support the Trigger-threshold-target model and indicate that the occurrence of speech onset delay in AS individuals depends on the location of cortical functional reallocation, which favors perception in AS-SOD and language in AS-NoSOD.


Subject(s)
Auditory Perception/physiology , Autism Spectrum Disorder/physiopathology , Language Development Disorders/physiopathology , Prefrontal Cortex/physiopathology , Temporal Lobe/physiopathology , Acoustic Stimulation , Adolescent , Adult , Auditory Cortex/physiopathology , Female , Humans , Male , Neuronal Plasticity/physiology , Young Adult
7.
Rev. esp. pediatr. (Ed. impr.) ; 70(6): 327-332, nov.-dic. 2014. tab, graf
Article in Spanish | IBECS | ID: ibc-133423

ABSTRACT

El documento presenta la situación de la Sección de Urgencias-Cuidados Intensivos Pediátricos (CIP). Tras una introducción que pretende enmarcar la sección en su contexto histórico y demográfico, se describe la misión, visión, valores y la cartera de servicios de la sección. Posteriormente se detalla la actividad asistencial, la labor docente y los proyectos y líneas de investigación. Para finalizar, se explica brevemente nuestro compromiso con la calidad y seguridad del paciente y nuestras líneas estratégicas para la integración con atención primaria (AU)


The paper presents the status of the Section of Emergency-CIP. Alter an introductory section aims to frame the historical and demographic background, mission, vision, values and the range 01 services described in section. Subsequently those services, the teaching and research projects and detailed lines. To conclude briefly describes our commitment to quality and patient safety and lar our strategic integration lines with primary care (AU)


Subject(s)
Humans , Emergency Service, Hospital/organization & administration , Pediatrics/organization & administration , Intensive Care Units, Pediatric/organization & administration , Critical Illness , Hospitals, University/organization & administration , Comprehensive Health Care/organization & administration , Delivery of Health Care, Integrated/organization & administration
8.
J Anim Breed Genet ; 131(6): 483-6, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24862839

ABSTRACT

Identifying the action of natural selection from patterns of standing genetic variation has long been of interest to the population genetic community. Thanks to the availability of large single-nucleotide polymorphism (SNP) data sets for many species and of high-throughput SNP genotyping methods, whole-genomic surveys to detect selective sweeps are now possible. Knowing the ancestral allele increases the power to detect selection. We present here a comparative genomic approach to determine the putative ancestral allele of bovine SNPs deposited in public databases. We analysed 19,551,488 SNPs and identified the putative ancestral allele for 14,339,107 SNPs. Our predicted ancestral alleles were in agreement with ancestral alleles detected by genotyping outgroup species for 97% SNPs from the BovineSNP50 BeadChip. This comparison indicates that our comparative genomic-based approach to identify putative ancestral alleles is reliable.


Subject(s)
Cattle/genetics , Polymorphism, Single Nucleotide , Animals , Databases, Genetic , Genotyping Techniques
9.
Gastroenterol Clin Biol ; 34(10): 554-61, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20739132

ABSTRACT

AIM: The purpose of this study was to measure the bone mineral density (BMD) of children with Crohn's disease (CD) and to prospectively assess its evolution. PATIENTS AND METHODS: A total of 27 children (20 boys, seven girls), aged 12.1±2.5 years, were recruited at the time of CD diagnosis. Dual-energy X-ray absorptiometry (DEXA) was used to measure BMD, expressed as Z scores for chronological age (BMD/CA) and bone age (BMD/BA). One year later, BMD was measured again to identify any correlations with disease activity [group A (active disease) vs group R (remission)]. RESULTS: BMD/CA and BMD/BA were negatively correlated with delay in diagnosis (P<0.0001 and P<0.05, respectively). BMD/CA was less than -2 standard deviation (SD) in nine patients and BMD/BA was less -2 SD in four patients. At the follow-up, the increase in BMD was smaller in group A (n=14), whether expressed as absolute values (-0.002 vs 0.040 g/cm(2) per year; P<0.024) or as percentages (-0.2 vs 6.6%; P<0.041); changes in BMD/CA (-0.5 vs -0.1 SD/year) and BMD/BA (-0.3 vs 0 SD/year) did not differ. CONCLUSION: Diagnostic delay greatly affects BMD in children with CD even prior to corticosteroid therapy. The risk of low BMD increases with persistent CD activity, although the risk is reduced in association with bone maturation delay.


Subject(s)
Absorptiometry, Photon , Bone Density , Crohn Disease/complications , Crohn Disease/diagnosis , Osteoporosis/diagnosis , Osteoporosis/etiology , Adolescent , Child , Female , Follow-Up Studies , Humans , Male , Prospective Studies , Reference Values
10.
Neurosci Behav Physiol ; 35(1): 59-70, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15739789

ABSTRACT

The goal of these experiments was to evaluate the effect of stimulus evoked input and post spike refractoriness on the shapes of post stimulus time histograms (PSTHs). The time courses of spontaneous and/or evoked activity were studied in 153 neurons located predominantly in the dorsal cochlear nucleus in cats anesthetized with Nembutal. Tone bursts were presented to the ipsilateral ear in a free sound field. About half the cells were characterized by the pauser/build-up type of PSTH. Marked refractoriness was evidenced by relatively long recovery times of the hazard functions of spontaneous and tone-evoked spike activity. On presentation of tonal bursts, the time dependence of the probability of the first spike in the absence of a preceding spike (expected spike density function) was greater than the PSTH (actual spike density function). The initial PSTH peak with pause was shaped primarily by stimulus evoked input, whereas refractoriness tended to diminish the build-up portion of the PSTH. In chopper cells, PSTH peaks were usually not reflected in expected spike density functions showing that post spike refractoriness plays a major role in shaping the PSTH. In primary-like cells, refractoriness was small and had little effect on the shape of the PSTH. Some presumptively inhibitory cells showed a tendency to burst discharges with non-monotonic hazard functions. A very small number of cells showed a tendency to internal tuning to a defined signal periodicity.


Subject(s)
Action Potentials/physiology , Cochlear Nucleus/cytology , Neurons/physiology , Acoustic Stimulation/methods , Animals , Cats , Models, Neurological , Reaction Time/physiology , Time Factors
11.
Ross Fiziol Zh Im I M Sechenova ; 89(6): 682-99, 2003 Jun.
Article in Russian | MEDLINE | ID: mdl-12966707

ABSTRACT

The temporal properties of spontaneous and (or) evoked discharges of 157 neurons localized in dorsal cochlear nucleus of anaesthetized cats have been studied. Tone bursts were presented at stimulus best frequency in a free field from the side of ipsilateral ear. About half of cells were characterized by paused or build-up types of the discharge. For all such units a long lasting post-spike decrease in excitability could be seen from the analysis of hazard functions of spontaneous and evoked activity. As a result, the time dependence of conditional probability of the first crossing of the threshold (under condition of an absence of previous response spikes) or expecting probability function (EPF) were over the usual peristimulus histograms. Units with chopper discharges usually did not demonstrate alternative peaks in EPF. We interpreted this fact as evidence that chopper discharge pattern is a result of strong post spike decrease in excitability. Such pattern doesn't demonstrate an existence of real periodicity of the unit. In primary-like units the hazard functions demonstrated only minor after-spike decrease of excitability, and the EPFs were similar to the initial part of peristimulus histograms. Type II units (presumably inhibitory cells) were characterized by non-monotonous hazard functions and by a tendency to burst response patterns. In some cells, we observed a tendency to existence of real intrinsic oscillations both in the EPFs and hazard functions.


Subject(s)
Action Potentials/physiology , Cochlear Nucleus/physiology , Electrophysiology/statistics & numerical data , Neurons/physiology , Acoustic Stimulation , Animals , Cats , Microelectrodes , Models, Neurological , Models, Statistical , Reaction Time/physiology
12.
Nucleic Acids Res ; 30(1): 94-7, 2002 Jan 01.
Article in English | MEDLINE | ID: mdl-11752264

ABSTRACT

A large collection of T-DNA insertion transformants of Arabidopsis thaliana has been generated at the Institute of Agronomic Research, Versailles, France. The molecular characterisation of the insertion sites is currently performed by sequencing genomic regions flanking the inserted T-DNA (FST). The almost complete sequence of the nuclear genome of A.thaliana provides the framework for organising FSTs in a genome oriented database, FLAGdb/FST (http://genoplante-info.infobiogen.fr). The main scope of FLAGdb/FST is to help biologists to find the FSTs that interrupt the genes in which they are interested. FSTs are anchored to the genome sequences of A.thaliana and positions of both predicted genes and FSTs are shown graphically on sequences. Requests to locate the genomic position of a query sequence are made using BLAST programs. The response delivered by FLAGdb/FST is a graphical representation of the putative FSTs and of predicted genes in a 20 kb region.


Subject(s)
Arabidopsis/genetics , DNA Transposable Elements , Databases, Genetic , Genome, Plant , Arabidopsis/physiology , Chromosome Mapping , Computer Graphics , DNA, Plant/genetics , Database Management Systems , Genes, Plant , Information Storage and Retrieval , Internet , Mutagenesis, Insertional , Plant Proteins/genetics , Plant Proteins/physiology , Transformation, Genetic
14.
J Appl Toxicol ; 21 Suppl 1: S87-94, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11920927

ABSTRACT

Soman, a potent acetylcholinesterase inhibitor, induces status epilepticus in rats followed by conspicuous neuropathology, most prominent in piriform cortex and the CA3 region of the hippocampus. Cholinergic seizures originate in striatal-nigral pathways and with fast-acting agents (soman) rapidly spread to limbic related areas and finally culminate in a full-blown status epilepticus. This leads to neurochemical changes, some of which may be neuroprotective whereas others may cause brain damage. Pretreatment with lithium sensitizes the brain to cholinergic seizures. Likewise, other agents that increase limbic hyperactivity may sensitize the brain to cholinergic agents. The hyperactivity associated with the seizure state leads to an increase in intracellular calcium, cellular edema and metal delocalization producing an oxidative stress. These changes induce the synthesis of stress-related proteins such as heat shock proteins, metallothioneins and heme oxygenases. We show that soman-induced seizures cause a depletion in tissue glutathione and an increase in tissue 'catalytic' iron, metallothioneins and heme oxygenase-1. The oxidative stress induces the synthesis of stress-related proteins, which are indicators of 'stress' and possibly provide neuroprotection. These findings suggest that delocalization of iron may catalyze Fenton-like reactions, causing progressive cellular damage via free radical products.


Subject(s)
Chemical Warfare Agents/toxicity , Heat-Shock Proteins/biosynthesis , Heat-Shock Proteins/pharmacology , Oxidative Stress , Seizures/chemically induced , Soman/toxicity , Animals , Glutathione/analysis , Glutathione/metabolism , Heme Oxygenase (Decyclizing)/analysis , Heme Oxygenase (Decyclizing)/metabolism , Heme Oxygenase-1 , Iron/analysis , Iron/metabolism , Male , Metallothionein/analysis , Metallothionein/metabolism , Neuroprotective Agents/pharmacology , Rats , Rats, Wistar , Seizures/physiopathology
15.
J Neurophysiol ; 84(3): 1330-45, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10980006

ABSTRACT

Azimuth tuning of high-frequency neurons in the primary auditory cortex (AI) is known to depend on binaural disparity and monaural spectral (pinna) cues present in broadband noise bursts. Single-unit response patterns differ according to binaural interactions, strength of monaural excitatory input from each ear, and azimuth sensitivity to monaural stimulation. The latter characteristic has been used as a gauge of neural sensitivity to monaural spectral directional cues. Azimuth sensitivity may depend predominantly on binaural disparity cues, exclusively on monaural spectral cues, or on both. The primary goal of this study was to determine whether each cortical response pattern corresponds to a similar pattern in the medial geniculate body (MGB) or whether some patterns are unique to the cortex. Single-unit responses were recorded from the ventral nucleus (Vn) and lateral part of the posterior group of thalamic nuclei (Po), tonotopic subdivisions of the MGB. Responses to free-field presentation of noise bursts that varied in azimuth and sound pressure level were obtained using methods identical to those used previously in field AI. Many units were azimuth sensitive, i.e., they responded well at some azimuths, and poorly, if at all, at others. These were studied further by obtaining responses to monaural noise stimulation, approximated by reversible plugging of one ear. Monaural directional (MD) cells were sensitive to the azimuth of monaural noise stimulation, whereas binaural directional (BD) cells were either insensitive to its azimuth or monaurally unresponsive. Thus BD and MD cells show differential sensitivity to monaural spectral cues. Monaural azimuth sensitivity could not be used to interpret the spectral sensitivity of predominantly binaural cells that exhibited strong binaural facilitation because they were either unresponsive or poorly responsive to monaural stimulation. The available evidence suggests that some such cells are sensitive to spectral cues. The results do not indicate the presence of any response types in AI that are not present in the MGB. Vn and Po contain similar classes of MD and BD cells. Because Po neurons project to the anterior auditory field, neurons in this cortical area also are likely to exhibit differential sensitivity to binaural disparity and monaural spectral cues. Comparison of these MGB data with a published report of cochlear nucleus (CN) single-unit azimuth tuning shows that MGB sensitivity to spectral cues is considerably stronger than CN sensitivity.


Subject(s)
Auditory Threshold/physiology , Cues , Geniculate Bodies/physiology , Sound Localization/physiology , Acoustic Stimulation , Action Potentials/physiology , Animals , Auditory Cortex/physiology , Cats , Electrodes, Implanted , Geniculate Bodies/cytology , Neurons/physiology , Reaction Time/physiology , Thalamic Nuclei/physiology
16.
Pediatr Res ; 48(1): 43-9, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10879799

ABSTRACT

Congenital aortic coarctation is well tolerated by the fetus because the foramen ovale and ductus arteriosus equalize intracardiac and great arteries pressures and shunts. The pathologic consequences only emerge after birth with closure of the foramen ovale and ductus arteriosus. There is, however, no documentation of myocardial effects in utero of the left ventricular (LV) pressure overload induced by aortic banding. We investigated whether prenatal aortic banding could be detrimental at the structural and/or functional level. The goal of the present study was to investigate the cardiac effects of LV pressure overload in a fetal lamb model. Nine fetal lambs underwent preductal banding of the aortic arch in utero at midgestation (CoA group), whereas their twins underwent sham surgery. All fetuses were studied between 27 and 37 d after surgery for LV pressure, anatomic and histologic anomalies, and steady state sarcoendoplasmic reticulum calcium ATPase (SERCA 2a) mRNA and protein levels and pump activity. Surgery resulted in severe aortic coarctation in all the animals in the CoA group and was associated with a 65% increase in the LV weight to body weight ratio relative to the sham-operated group (p < 0.001). Hemodynamic and histologic studies showed an evolutionary pattern depending on duration of the experimental coarctation with a shift occurring at 30 d of coarctation. The initial response of cardiomyocytes to ventricular overload was hypertrophy of the myocytes, followed by myocyte hyperplasia. Compared with sham, there was an apparent decrease in the percentage of binucleated cells in the CoA group after 30 d of coarctation. The earliest response to LV pressure overload appears to occur at the molecular level. Indeed, sarcoendoplasmic reticulum calcium ATPase (SERCA 2a) mRNA levels fell significantly to only 28.6% of the sham group value (p = 0.023), independently of the duration of coarctation. In the fetal lamb, the pressure overload-induced hypertrophy resulting from progressive aortic coarctation leads to hemodynamic and lesional abnormalities and slows ontogenic maturation.


Subject(s)
Hypertrophy, Left Ventricular/embryology , Hypertrophy, Left Ventricular/physiopathology , Animals , Aorta, Thoracic/embryology , Aorta, Thoracic/physiology , Aortic Coarctation , Calcium-Transporting ATPases/genetics , Disease Models, Animal , Female , Gene Expression Regulation, Developmental , Gene Expression Regulation, Enzymologic , Gestational Age , Heart/embryology , Hemodynamics , Myocardium/pathology , Pregnancy , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Sheep
17.
Cell Mol Biol (Noisy-le-grand) ; 46(4): 699-707, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10875433

ABSTRACT

In this overview we bring together certa in facts and concepts that support the theory that the aging of "disease-free" brain is a consequence of the accumulated cellular-molecular modifications caused by oxygen free radicals. The relevance of transition metals, especially iron ions, in the production of oxygen free radicals, initiation of oxidative chain-reactions and in site-specific molecular modifications is documented. Mitochondria are identified as the major source of oxygen free radicals, and mitochondrial DNA is a likely target. Special attention is given to iron-sulfur clusters as sources of reactive iron and sites of modifications. Potential mechanisms by which oxygen free radicals can alter membrane receptors and intracellular signaling are cited. Although the evidence is still correlative, the oxygen free radical theory has strong experimental support and has promise for facilitating a better understanding of the "disease-free", aging brain.


Subject(s)
Aging , Brain/metabolism , Brain/pathology , Free Radicals/metabolism , Metals/metabolism , Oxygen/metabolism , Animals , Humans , Iron/metabolism , Mitochondria/metabolism , Oxidation-Reduction , Transcription Factors/metabolism
18.
Cell Mol Biol (Noisy-le-grand) ; 46(3): 619-26, 2000 May.
Article in English | MEDLINE | ID: mdl-10872748

ABSTRACT

Global hypoxia preconditioning provides neuroprotection against a subsequent, normally damaging challenge. While the mechanistic pathways are unknown, changes in the expression of stress-related proteins are implicated. Hypoxia preconditioning attenuates the brain edema and neuropathology associated with kainic acid-induced status epilepticus in a protein synthesis-dependent manner when a kainic acid challenge is given up to one week post-preconditioning. Kainic acid initiates a glutamate-driven status epilepticus causing a Ca2+ and oxidative stress, resulting in injury to the piriform cortex and hippocampus. Stress-related gene expression [e.g. metallothioneins (MTs), heme oxygenase-1 (HO-1)] is enhanced during seizures in vulnerable brain areas, (e.g. piriform cortex). This study explores the effects of hypoxia preconditioning on expression of MT-1, MT-2 and HO-1 before and after kainic acid-induced seizures. Analysis of MT-1, MT-2 and HO-1 expression, through Western and Northern blotting, indicates that there is a variable pattern of induction and suppression of these two genes following hypoxia preconditioning alone as well as after kainic acid-induced seizures compared to non-preconditioned animals. These findings suggest that hypoxia preconditioning induces an adaptive response that prevents kainic acid seizure-associated neuropathology even when robust seizures occur. This may involve a variety of stress-related proteins, working in concert, each with their own individual expression profiles. Induction of this type of neuroprotection pharmacologically, or through preconditioning, will provide a better understanding of the stress response in brain.


Subject(s)
Heme Oxygenase (Decyclizing)/biosynthesis , Hypoxia/metabolism , Metallothionein/biosynthesis , Seizures/metabolism , Animals , Cerebral Cortex/metabolism , Disease Models, Animal , Heme Oxygenase (Decyclizing)/genetics , Heme Oxygenase-1 , Hippocampus/metabolism , Kainic Acid , Male , Metallothionein/genetics , Rats , Rats, Wistar , Seizures/chemically induced , Time Factors
19.
Cell Mol Biol (Noisy-le-grand) ; 46(3): 649-55, 2000 May.
Article in English | MEDLINE | ID: mdl-10872751

ABSTRACT

A sensitive iron assay was developed for measuring non-heme and loosely bound iron in regions of rat brain. The method is based on the salicylate trapping of hydroxyl radicals generated from ascorbate-driven redox cycling of Fe3+-EDTA. This assay has high sensitivity (about 20 nM) because of amplification obtained with redox-cycling and fluorescent detection of the salicylate hydroxylation product, 2,5-dihydroxybenzoate. The assay detects iron as Fe2+ and Fe3+ combined. Values of non-heme and loosely bound iron are given for three areas of cortex, caudate, hippocampus, thalamus and brainstem of the rat brain.


Subject(s)
Brain Chemistry , Brain/metabolism , Iron Chelating Agents/metabolism , Iron/analysis , Salicylic Acid/metabolism , Animals , Calibration , Chlorides , Ferric Compounds/metabolism , Male , Oxidation-Reduction , Rats , Rats, Sprague-Dawley
20.
J Neurophysiol ; 83(2): 907-25, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10669504

ABSTRACT

We tested two hypotheses to determine whether dorsal cochlear nucleus (DCN) neurons are specialized to derive directionality from spectral notches: DCN neurons exhibit greater spectral-dependent directionality than ventral cochlear nucleus (VCN) neurons, and spectral-dependent directionality depends on response minima (nulls) produced by coincidence of best frequency (BF) and spectral-notch center frequency. Single-unit responses to 50-ms noise and tone bursts were recorded in barbiturate-anesthetized cats (BFs: 4-37 kHz). Units were classified using BF tone poststimulus time histograms. Pauser, onset-G (type II interneurons), and some chopper units were recorded from the DCN. Primary-like, onset-CIL (onset other than onset-G), and most choppers in the sample were recorded from the VCN. Many pauser and onset-G units were highly directional to noise. Chopper, onset-CIL, and primary-like units (collectively referred to as C-O-P units) were not. The difference in directionality depends on a monaural mechanism as pausers were more directional to monaural noise than C-O-P units. Contralateral inhibition produced a small increase in pauser directionality to noise simulation but had no effect on directionality of C-O-P units. Pauser and C-O-P units exhibited similar low directionality to BF tone, showing that the difference in noise directionality between groups depends on spectral cues. These results show that spectral-dependent directionality is a DCN specialization. Azimuth functions of highly directional units exhibited response nulls, and there was a linear relationship between BFs in the range of 8-13 kHz and azimuthal locations of nulls. This relationship parallels the known spatial distribution of spectral-notch center frequencies on the horizontal plane. Furthermore spatial receptive fields of pausers show response nulls that follow the expected diagonal trajectory of the spectral notch in this frequency range. These results show that DCN spectral-dependent directionality depends on response nulls produced by coincidence of unit BF and spectral-notch center-frequency.


Subject(s)
Cochlear Nucleus/physiology , Ear, External/physiology , Sound Localization/physiology , Acoustic Stimulation , Action Potentials/physiology , Animals , Auditory Threshold/physiology , Cats , Neural Inhibition/physiology , Noise
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