CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2009
Li-Hong Long
SUMMARY 1Age-related impairments in hippocampus-dependent spatial learning and memory are not associated with a loss of neurons, but may be related to synaptic changes. In the present study, we analysed the behavioural performance of adult, middle-aged and old Wistar rats using the Morris water maze, as well as the structure of synapses and the expression of autophosphorylated Ca2+/calmodulin-dependent protein kinase II at threonine 286 (pThr286-,CaMKII), a key post-synaptic protein in the CA1 stratum radiatum, in the same rats. 2Old Wistar rats showed significant cognitive deficits. Synaptic density, the area of post-synaptic densities and the total number of synapses in the CA1 stratum radiatum of old rats were significantly decreased compared with adult rats. The decrease in autophosphorylated pThr286-,CaMKII was age dependent. 3These findings reveal that age-related impairments in learning and memory are associated with synaptic atrophy. The decreased expression of pThr286-CaMKII may result in reduced synaptic function with ageing. [source]

The effect of prenatal hypoxia on brain development: short- and long-term consequences demonstrated in rodent models

DEVELOPMENTAL SCIENCE, Issue 4 2006
Hava Golan
Hypoxia (H) and hypoxia-ischemia (HI) are major causes of foetal brain damage with long-lasting behavioral implications. The effect of hypoxia has been widely studied in human and a variety of animal models. In the present review, we summarize the latest studies testing the behavioral outcomes following prenatal hypoxia/hypoxia-ischemia in rodent models. Delayed development of sensory and motor reflexes during the first postnatal month of rodent life was observed by various groups. Impairment of motor function, learning and memory was evident in the adult animals. Activation of the signaling leading to cell death was detected as early as three hours following H/HI. An increase in the counts of apoptotic cells appeared approximately three days after the insult and peaked about seven days later. Around 14,20 days following the H/HI, the amount of cell death observed in the tissue returned to its basal levels and cell loss was apparent in the brain tissue. The study of the molecular mechanism leading to brain damage in animal models following prenatal hypoxia adds valuable insight to our knowledge of the central events that account for the morphological and functional outcomes. This understanding provides the starting point for the development and improvement of efficient treatment and intervention strategies. [source]

Epidemiology and natural course of social fears and social phobia,

ACTA PSYCHIATRICA SCANDINAVICA, Issue 2003
H.-U. Wittchen
Objective: To summarize epidemiological studies providing data on prevalence, incidence, comorbidity, natural course, risk factors and consequences of social phobia (SP). Method: Data from cross-sectional studies and prospective longitudinal studies in particular are considered. Results: These studies portray SP as a frequent mental disorder, which begins typically in early adolescence, and is highly comorbid with other anxiety disorders, as well as secondary depression and substance abuse disorders. Several possible risk factors have already been identified for the onset and unfavorable course of SP; some of them have been tested in prospective longitudinal studies. SP is a chronic disorder when compared with other mental disorders and when subclinical symptomatic levels are considered. Impairment caused by SP is considerable and increases over a patient's life span. The negative impact of SP is not only reflected in subjective well-being and reduced quality of life but also in social role functioning, and it impacts negatively on career progression. Conclusion: Prospective longitudinal studies in representative samples drawn from the general population provide information that allows the overall direct and indirect costs of the disorder (treatment costs, disability, social welfare) to be determined, and enables an improvement in long-term care strategies as well as preventive efforts to be established. [source]

Impairment of cerebral autoregulation in diabetic patients with cardiovascular autonomic neuropathy and orthostatic hypotension

DIABETIC MEDICINE, Issue 2 2003
B. N. Mankovsky
Abstract Aims Impaired cerebrovascular reactivity and autoregulation has been previously reported in patients with diabetes mellitus. However, the contribution of cardiovascular diabetic autonomic neuropathy and orthostatic hypotension to the pathogenesis of such disturbances is not known. The purpose of this study was to evaluate cerebral blood flow velocity in response to standing in patients with diabetes and cardiovascular autonomic neuropathy with or without orthostatic hypotension. Methods We studied 27 patients with diabetes,eight had cardiovascular autonomic neuropathy and orthostatic hypotension (age 46.4 ± 13.5 years, diabetes duration 25.0 ± 11.0 years), seven had autonomic neuropathy without hypotension (age 47.3 ± 12.7 years, diabetes duration 26.4 ± 12.1 years), and 12 had no evidence of autonomic neuropathy (age 44.1 ± 13.8 years, diabetes duration 17.1 ± 10.2 years),and 12 control subjects (age 42.6 ± 9.7 years). Flow velocity was recorded in the right middle cerebral artery using transcranial Doppler sonography in the supine position and after active standing. Results Cerebral flow velocity in the supine position was not different between the groups studied. Active standing resulted in a significant drop of mean and diastolic flow velocities in autonomic neuropathy patients with orthostatic hypotension, while there were no such changes in the other groups. The relative changes in mean flow velocity 1 min after standing up were ,22.7 ± 16.25% in patients with neuropathy and orthostatic hypotension, +0.02 ± 9.8% in those with neuropathy without hypotension, ,2.8 ± 14.05% in patients without neuropathy, and ,9.2 ± 15.1% in controls. Conclusions Patients with diabetes and cardiovascular autonomic neuropathy with orthostatic hypotension show instability in cerebral blood flow upon active standing, which suggests impaired cerebral autoregulation. [source]

"Must We Overlook All Impairment of Our Interests?"

DIPLOMATIC HISTORY, Issue 4 2005
Debating the Foreign Aid Role of the Export-Import Bank
First page of article [source]

Visual, auditory and cross-modal processing of linguistic and nonlinguistic temporal patterns among adult dyslexic readers

DYSLEXIA, Issue 2 2005
Ann Meyler
Abstract This study examined visual, auditory, and cross-modal temporal pattern processing at the nonlinguistic and sublexical linguistic levels, and the relationships between these abilities and decoding skill. The central question addressed whether dyslexic readers are impaired in their perception of timing, as assessed by sensitivity to rhythm. Participants were college-level adult dyslexic and normal readers. The dyslexic adults evidenced generalized impairment in temporal processing: they were less accurate and slower than normal readers when required to detect the temporal gap that differentiated pairs of patterns. Impairment was greatest when processing visual syllables. Temporal pattern processing correlated to decoding ability only among normal readers. It is suggested that high-functioning dyslexics may cope with temporal processing problems by adopting a predominantly holistic, orthographic strategy when decoding. It is proposed that there may be cumulative effects of processing demands from different sources including modality, stimulus complexity, and linguistic demands, and that combinations of these may interact to impact temporal processing ability. Moreover, there may be fundamentally distinct and dissociable temporal processing abilities, each of which may be differently linked developmental dyslexia. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Association between Endothelial Function and Chronotropic Incompetence in Subjects with Chronic Heart Failure Receiving Optimal Medical Therapy

ECHOCARDIOGRAPHY, Issue 3 2010
M.D., Timothy J. Vittorio M.S.
Objective: Impairment of flow-mediated, endothelium-dependent vasodilatation (FMD) of the brachial artery identifies peripheral endothelial dysfunction in subjects with chronic congestive heart failure (CHF) and is associated with increased morbidity and mortality. To further elucidate the interaction of peripheral and central mechanisms in the syndrome of CHF, we examined the association between endothelial function and chronotropic incompetence, an emerging prognostic marker in CHF. Methods: Thirty subjects with stable New York Heart Association (NYHA) functional class II,III CHF were studied. A vascular ultrasound study was performed to measure brachial artery FMD. The percentage of age-adjusted maximal predicted heart rate (MPHR) reached during cardiopulmonary exercise tolerance testing (CPETT) was used to assess the degree of chronotropic competence. All patients received ACE inhibitors and ,-adrenoceptor blockers. Results: Brachial artery FMD averaged 1.3 ± 2.4% and age-adjusted % MPHR 74.1 ± 11.7%. FMD correlated with % MPHR among all patients (r = 0.60, P = 0.01). FMD and resting heart rate (RHR) did not significantly correlate (r = 0.13, P = 0.55). Conclusions: FMD, a measure of peripheral endothelial dysfunction, and % MPHR, a central determinant of cardiac output, are moderately correlated in heart failure patients receiving optimal medical therapy. Whether a cause-effect relationship underlies this association remains to be investigated. (Echocardiography 2010;27:294-299) [source]

An Abnormal Right Ventricular Apical Angle is Indicative of Global Right Ventricular Impairment

ECHOCARDIOGRAPHY, Issue 5 2006
Angel López-Candales M.D.
The presence of right ventricular (RV) dysfunction is an adverse prognostic indicator but current echocardiographic methods have some limitations. RV apical angles in systole and diastole were correlated with known parameters of RV function in patients without pulmonary hypertension (Group 1) and in patients with pulmonary hypertension (Group 2). RV apical angles were significantly smaller in both systole (22 ± 7°) and diastole (33 ± 6°) in Group 1 patients when compared to Group 2 (54 ± 18°, p < 0.0001 and 59 ± 17°, p < 0.0001, respectively). RV apical angles, both in systole and diastole, were strongly correlated with RV end-systolic area (R = 0.89, p < 0.0001) and end-diastolic area (R = 0.81, p < 0.0001), respectively. Similarly, the apical systolic and diastolic angle correlated well with decreased tricuspid annular plane systolic excursion (TAPSE, R =,0.76 and R =,0.73, p < 0.001) as well as with decreased RV fractional area change (R =,0.81 and R =,0.77, p < 0.001). Therefore, we conclude that this new measurement of RV apical angle is simple and useful to quantify RV apical structural and functional abnormalities that are well correlated with global RV impairment in patients with chronic pulmonary hypertension. [source]

Impairment due to cannabis and ethanol: clinical signs and additive effects

ADDICTION, Issue 6 2010
Jørgen G. Bramness
ABSTRACT Aims Studies have shown that the impairing effects of ,-9-tetrahydrocannabinol (THC) are dose-related. Cannabis intake increases the risk of traffic accidents. The purpose of this study was to see how different clinical tests and observations were related to blood THC concentrations and to determine whether the combined influence of THC and ethanol was different from either drug alone. Design A retrospective cross-sectional forensic database study. Setting Drivers apprehended by the police suspected of driving under the influence of alcohol other drugs. Participants We investigated 589 cases positive for THC only. In addition, 894 cases with THC and ethanol were included. A comparison was made with 3480 drivers with only ethanol in their blood and 79 drivers who tested negative. Measurements Data were analytical results of blood samples and the 27 clinical tests and observations included in the Norwegian clinical test for impairment (CTI). Findings No relationship was found between blood THC concentration and most of the CTI tests. Blood THC concentration was, however, related to conjunctival injection, pupil dilation and reaction to light and to the overall risk of being judged impaired. When THC and ethanol were detected together the risk of being judged impaired was increased markedly. Conclusions This study demonstrates that cannabis impairs driving ability in a concentration-related manner. The effect is smaller than for ethanol. The effect of ethanol and cannabis taken simultaneously is additive. Conjunctival injection, dilated pupils and slow pupil reaction are among the few signs to reveal THC influence. [source]

A Study of 43 Patients with Panayiotopoulos Syndrome, a Common and Benign Childhood Seizure Susceptibility

EPILEPSIA, Issue 1 2003
Christina Lada
Summary: ,Purpose: To determine prevalence, clinical, EEG features, and prognosis of Panayiotopoulos syndrome and to examine the proposition that clinical manifestations are more important than EEG findings. Methods: We analyzed retrospectively the clinical and EEG records of 1,340 children with one or more focal seizures seen in the last 18 years, supplemented with a prospective study from 1998. Panayiotopoulos syndrome was defined by clinical criteria, mainly ictal emesis, irrespective of EEG findings. Results: We analyzed 43 of 90 patients with Panayiotopoulos syndrome who were seizure free >2 years. Girls predominated. Mean age at first seizure was 5 years. Seizures consisted mainly of autonomic manifestations; ictal emesis was often the first symptom, culminating in vomiting in 86%. Of nonautonomic manifestations, lateral eye deviation was the most common; visual symptoms were exceptional. Impairment of consciousness ensued in all seizures, half of which ended with hemi or generalized convulsions. Nearly 46.5% of cases had at least one seizure >30 min, constituting autonomic status epilepticus. Seizures during sleep (84%) were more common than those in wakefulness. EEG showed occipital spikes in 29 patients. Of the other 14 cases, five had extraoccipital abnormalities or brief generalized discharges, and nine had normal awake and sleep EEG. Prognosis was excellent. All 43 children have been free of seizures for ,2 years, 53% having a single seizure, and 47%, an average two to three seizures. Conclusions: Panayiotopoulos syndrome is common and needs wider recognition. EEG shows occipital or extraoccipital abnormalities, is normal in one third of patients, and does not determine clinical manifestations or prognosis, which is excellent despite the high prevalence of lengthy seizures. [source]

Impairment of dendritic cell function by excretory-secretory products: A potential mechanism for nematode-induced immunosuppression

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2007
Mariela Segura
Abstract To determine whether helminth-derived products modulate dendritic cell (DC) function, we investigated the effects of excretory-secretory products (ES) and adult worm homogenate (AWH) derived from the gastrointestinal nematode Heligmosomoides polygyrus (Hp) on murine bone marrow-derived DC (BMDC). Compared to the TLR9 ligand CpG, Hp-derived products alone failed to induce DC activation. ES, but not AWH, inhibited BMDC cytokine and chemokine production and co-stimulatory molecule expression (CD40, CD86 and MHC class,II) induced by TLR ligation. TLR ligand-independent, PMA-induced DC activation was unaffected by ES. Recipients of ES-treated BMDC pulsed with OVA had suppressed Ab responses in vivo, irrespective of the Th1 or Th2 isotype affiliation, compared to recipients of control OVA-pulsed BMDC. Importantly, suppression occurred even in the presence of the potent type,1 adjuvant CpG. In contrast to untreated OVA-pulsed BMDC, ES-treated BMDC pulsed with OVA had reduced co-stimulatory molecule and cytokine expression. CD4+CD25+Foxp3, T cells, which secreted high IL-10 levels, were generated in co-cultures of OT-II OVA-specific TCR-transgenic CD4+ T cells and ES-treated BMDC. These IL-10-secreting T cells suppressed effector CD4+ T cell proliferation and IFN-, production, the latter effect mediated by an IL-10-dependent mechanism. Together, these results demonstrate that nematode ES impaired DC function and suppressed both Th1 and Th2 adaptive immune responses possibly by inducing regulatory T cells. [source]

CCR6 has a non-redundant role in the development of inflammatory bowel disease

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2003
Rosa Varona
Abstract Antigen-loaded tissues such as the intestinal mucosa must simultaneously elicit appropriate immune response to innocuous bacteria and food proteins, and to potentially harmful antigens. Impairment of the mechanisms controlling this response may mediate the excessive immune reaction that can lead to tissue destruction and inflammatory intestinal diseases, including inflammatory bowel disease. The intestinal epithelium influences local immune responses through the expression of adhesion molecules, costimulatory factors, cytokines and chemokines. CCL20, a ,-chemokine expressed in epithelia from colon and other intestinal tissue, plays a role in immune responses of intestinal mucosa, as deduced from the defects in intestinal leukocyte homeostasis shown by mice lacking CCR6, the CCL20 receptor. We studied the response of CCR6-deficient mice in two models of inflammatory bowel disease. The data show that absence of CCR6 resulted in less severe intestinal pathology in animals treated with dextran sodium sulfate. Conversely, CCR6 deficiency alters leukocyte homeostasis and the cytokine environment in the intestinal mucosa; these changes are sufficient to confer susceptibility to trinitrobenzene sulfonic acid-induced intestinal inflammation in the otherwise resistant C57BL/6J mouse strain. These results suggest that the CCR6/CCL20 axis has a critical, non-redundant role in the in vivo control of immune responses in the intestine. [source]

Impairment of CaMKII activation and attenuation of neuropathic pain in mice lacking NR2B phosphorylated at Tyr1472

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2010
Shinji Matsumura
Abstract Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a key mediator of long-term potentiation (LTP), which can be triggered by N -methyl- d -aspartate (NMDA) receptor-mediated Ca2+ influx. We previously demonstrated that Fyn kinase-mediated phosphorylation of NR2B subunits of NMDA receptors at Tyr1472 in the dorsal horn was involved in a neuropathic pain state even 1 week after nerve injury. Here we show that Y1472F-KI mice with a knock-in mutation of the Tyr1472 site to phenylalanine did not exhibit neuropathic pain induced by L5 spinal nerve transection, whereas they did retain normal nociceptive responses and induction of inflammatory pain. Phosphorylation of NR2B at Tyr1472 was only impaired in the spinal cord of Y1472F-KI mice among the major phosphorylation sites. There was no difference in the Ca2+ response to glutamate and sensitivity to NMDA receptor antagonists between naive wild-type and Y1472F-KI mice, and the Ca2+ response to glutamate was attenuated in the Y1472F-KI mice after nerve injury. Autophosphorylation of CaMKII at Thr286 was markedly impaired in Y1472F-KI mice after nerve injury, but there was no difference in phosphorylation of CaMKII at Thr305 or protein kinase C, at Thr674, and activation of neuronal nitric oxide synthase and microglia in the superficial layer of spinal cord between wild-type and Y1472F-KI mice after the operation. These results demonstrate that the attenuation of neuropathic pain is caused by the impaired NMDA receptor-mediated CaMKII signaling in Y1472F-KI mice, and suggest that autophosphorylation of CaMKII at Thr286 plays a central part not only in LTP, but also in persistent neuropathic pain. [source]

Impairment of conditioned freezing to tone, but not to context, in Fyn-transgenic mice: relationship to NMDA receptor subunit 2B function

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2005
N. Kojima
Abstract We previously demonstrated that transgenic mice overexpressing Fyn tyrosine kinase exhibit higher seizure susceptibility and enhanced tyrosine phosphorylation of several proteins, including the N -methyl-D-aspartate (NMDA) receptor subunit 2B (NR2B). In the present study, we analysed behavioural phenotypes, especially conditioned fear responses, of Fyn-transgenic (TG) mice to better understand the role of Fyn in learned emotional behaviour. Tone-dependent conditioned freezing was significantly attenuated in Fyn-TG mice, whereas context-dependent freezing was unaffected. Neither massed nor spaced conditioning ameliorated the attenuation of tone-dependent freezing. However, the selective NR2B antagonist ifenprodil, when administered before conditioning, restored tone-dependent freezing in Fyn-TG mice at a dose that did not affect freezing in wild-type (WT) mice. These results suggest that impairment of tone-dependent conditioned freezing in Fyn-TG mice is caused by disruption of the NR2B-containing NMDA receptor function. Tyrosine phosphorylation of brain proteins, including NR2B, was enhanced in Fyn-TG mice compared with that in WT mice. We also found that ifenprodil significantly suppressed the enhanced tyrosine phosphorylation. Thus, our data support the notion that NMDA receptor activity is tightly correlated with protein tyrosine phosphorylation, and Fyn might be one key molecule that controls tone-dependent conditioned freezing through the regulation of NMDA receptor function. [source]

Impairment of eyeblink conditioning in GluR,2-mutant mice depends on the temporal overlap between conditioned and unconditioned stimuli

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2001
Yasushi Kishimoto
Abstract Mice lacking the glutamate receptor subunit ,2 (GluR,2) are deficient in cerebellar long-term depression (LTD) at the parallel fibre,Purkinje cell synapses. We conducted delay and trace eyeblink conditioning with these mice, using various temporal intervals between the conditioned stimulus (CS) and unconditioned stimulus (US). During trace conditioning in which a stimulus-free trace interval (TI) of 250, 100 or 50 ms intervened between the 352-ms tone CS and 100-ms US, GluR,2-mutant mice learned as successfully as wild-type mice. Even in the paradigm with TI = 0 ms, in which the end of CS and onset of US are simultaneous, there was no difference between the GluR,2-mutant and wild-type mice in their acquisition of a conditioned response. However, in the delay paradigm in which the 452-ms CS overlapped temporally with the coterminating 100-ms US, GluR,2-mutant mice exhibited severe learning impairment. The present study together with our previous work [Kishimoto, Y., Kawahara, S., Suzuki, M., Mori, H., Mishina, M. & Kirino, Y. (2001) Eur. J. Neurosci.,13, 1249,1254], indicates that cerebellar LTD-independent learning is possible in paradigms without temporal overlap between the CS and US. On the other hand, GluR,2 and cerebellar LTD are essential for learning when there is CS,US temporal overlap, suggesting that the cerebellar neural substrates underlying eyeblink conditioning may change, depending on the temporal overlap of the CS and US. [source]

Impairment of binocular vision in the adult cat induces plastic changes in the callosal cortical map

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2001
Laurent Watroba
Abstract In the primary visual cortex of normally reared adult cat, neurons activated through the corpus callosum are almost entirely located at the 17/18 border. They display small receptive fields distributed along the central vertical meridian of the visual field and are orientation selective. Here we demonstrate that a few weeks of monocular deprivation or unilateral convergent strabismus produced in adulthood does not modify the cortical distribution of these neurons, but leads to an increase of their receptive field size mainly toward the ipsilateral hemifield and to a loss of their orientation selectivity. We conclude that manipulation of binocular vision in the adult modifies neither the location of the primary callosal cortical map nor its retinotopy. In contrast, it induces functional plastic changes in this map which lead to a significant widening of the area of visual space signalled through the corpus callosum. These plastic changes are interpreted as the result of the strengthening of normally hidden subthreshold synaptic inputs. [source]

Dimensions of Ambiguous Loss in Couples Coping With Mild Cognitive Impairment,

FAMILY RELATIONS, Issue 2 2007
Rosemary Blieszner
Abstract: We applied the theory of ambiguous loss to couples with mild cognitive impairment (MCI), an age-related decline in memory and other cognitive processes assumed not to interfere with daily activities or the maintenance of personal relationships. Face-to-face interviews with 67 older married couples revealed that lack of understanding about the behavioral manifestations of MCI resulted in much ambiguity in their lives. Fluctuations in the elders' functioning required spouses to alter their daily activities and responsibilities. As a result, couples often experienced distress that affected their emotional involvement with one another. Findings advance theoretical implications of ambiguous loss and provide educators and practitioners with suggestions for working with couples experiencing mild memory loss. [source]

Efficacy of Eletriptan in Migraine-Related Functional Impairment: Functional and Work Productivity Outcomes

HEADACHE, Issue 5 2007
Stephen D. Silberstein MD
Objective.,To provide a multidimensional assessment of the extent of functional impairment during an acute migraine attack, and of the improvement in functioning in response to treatment, using 4 concurrently administered scales: the 7-item work productivity questionnaire (PQ-7), the functional assessment in migraine (FAIM) activities and participation (FAIM-A&P) subscale, the FAIM-impact of migraine on mental functioning (FAIM-IMMF) subscale, and the traditional 4-point global functional impairment scale (FIS). Methods.,Outpatients with an International Classification of Headache Disorders diagnosis of migraine were randomized to double-blind treatment of a single attack with either oral eletriptan 20 mg (n = 192) once-daily, eletriptan 40 mg (N = 213) once-daily, or placebo (n = 208). Patients were encouraged to take study medication as soon as they were sure they were experiencing a typical migraine headache, after the aura phase (if present) had ended. Patients with moderate-to-severe functional impairment were identified on each of the 4 disability scales, and 2-hour functional response was compared between treatments. Results.,At baseline, the PQ-7 and FAIM-IMMF items that assessed ability to perform tasks requiring concentration, sustained work or attention, and ability to think quickly or spontaneously, were especially sensitive to the effects of mild headache pain, with 27% to 48% of patients (n = 92-112) reporting moderate-to-severe impairment. Only 11.3% of patients (n = 112) reported this level of impairment due to mild pain on the FIS. Functional response at 2 hours was significantly higher on eletriptan 40 mg versus placebo on the FAIM-A&P (63% vs 36%; n = 218; P < .0001); on the PQ-7 (56% vs 34%; n = 116; P= .0052); and on the FAIM-IMMF (50% vs 34%; n = 215; P= .017). These rates were all lower than the functional response rates on the FIS for eletriptan 40 mg (75%) and eletriptan 20 mg (70%) versus placebo (45%; P < .001). Conclusions.,In this exploratory analysis, use of multidimensional scales was found to provide a sensitive measure of headache-related functional impairment, especially for detecting clinically meaningful cognitive effects, and for detecting drug versus placebo differences. [source]

Impairment and recovery on a food foraging task following unilateral vestibular deafferentation in rats

HIPPOCAMPUS, Issue 4 2006
Yiwen Zheng
Abstract It has been suggested that the vestibular system may contribute to the development of higher cognitive function, especially spatial learning and memory that uses idiothetic cues (e.g., dead reckoning). However, few studies have been done using behavioral tasks that could potentially separate the animals' ability for dead reckoning from piloting. The food foraging task requires the animal to continuously monitor and integrate self-movement cues and generate an accurate return path. It has been shown that bilateral vestibular-lesioned rats were impaired on this task. The present study used the same task to further examine the contribution of vestibular information to spatial navigation by comparing unilateral and bilateral lesions and by testing the animals at different time points following the lesion. The results demonstrated that animals with unilateral vestibular deafferentation were impaired in performing the task in the dark at 3 months after the lesion, and this impairment disappeared at 6 months after the lesion. This supports the notion that vestibular information contributes to dead reckoning and suggests possible recovery of function over time after the lesion. Animals with bilateral vestibular deafferentation were not able to be tested on the foraging task because they exhibited behavior distinct from the unilateral-lesioned animals, with significant hesitation in leaving their home cage for as long as 6 months after the lesion. © 2005 Wiley-Liss, Inc. [source]

Reproductive Freedom, Self-Regulation, and the Government of Impairment in Utero

HYPATIA, Issue 1 2006
Shelley Tremain
This article critically examines the constitution of impairment in prenatal testing and screening practices and various discourses that surround these technologies. While technologies to test and screen (for impairment) prenatally are claimed to enhance women's capacity to be self-determining, make informed reproductive choices, and, in effect, wrest control of their bodies from a patriarchal medical establishment, I contend that this emerging relation between pregnant women and reproductive technologies is a new strategy of a form of power that began to emerge in the late eighteenth century. Indeed, my argument is that the constitution of prenatal impairment, by and through these practices and procedures, is a widening form of modem government that increasingly limits the field of possible conduct in response to pregnancy. Hence, the government of impairment in utero is inextricably intertwined with the government of the maternal body. [source]

Impairment and Disability: Constructing an Ethics of Care That Promotes Human Rights

HYPATIA, Issue 4 2001
JENNY MORRIS
The social model of disability gives us the tools not only to challenge the discrimination and prejudice we face, but also to articulate the personal experience of impairment. Recognition of difference is therefore a key part of the assertion of our common humanity and of an ethics of care that promotes our human rights. [source]

Sphingosine kinase inhibitor suppresses dendritic cell migration by regulating chemokine receptor expression and impairing p38 mitogen-activated protein kinase

IMMUNOLOGY, Issue 4 2007
In Duk Jung
Summary The migration of dendritic cells (DCs) to secondary lymphoid organs plays a crucial role in the initiation of adaptive immune responses. Although lipopolysaccharide enhances chemokine receptor 7 (CCR7) expression on DCs, the second signal for the migration of DCs toward the chemokine CCL19 remains unknown. In this study, we show that sphingosine kinase inhibitor (SKI) inhibits the migration of DCs toward CCL19 through the down-regulation of CCR7. Inhibition of p38 mitogen-activated protein kinase (MAPK) activation by SKI may be responsible for the SKI-mediated effects on the regulation of chemokine receptor expression. Impairment of DC migration by the inhibition of p38 MAPK and down-regulation of CCR7 expression may contribute to the protective effects of SKI in DC-related disorders. These results suggest that sphingosine kinase-mediated signalling plays a role in the innate and adaptive immune responses by altering DC migration. [source]