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Articles by Ann Wu in JoVE

 JoVE Clinical and Translational Medicine

Kronisk Sammandragning av ischiasnerven och Smärta Överkänslighet Testning i råttor


JoVE 3393 3/13/2012

School of Medical Sciences, University of New South Wales

På grund av enkelheten i operationen och den robusta beteende resultatet är kronisk förträngning av ischiasnerven en av den mest framstående djurmodeller av neuropatisk smärta. Inom 24 h efter kirurgi, smärta överkänslighet etablerad och kan mätas kvantitativt med användning av en von Frey-aesthesiometer (mekaniskt test) och plantar analgesi mätaren (termisk test).

Other articles by Ann Wu on PubMed

Screening for Iron Deficiency

TGF-beta Signaling Activates Steroid Hormone Receptor Expression During Neuronal Remodeling in the Drosophila Brain

Metamorphosis of the Drosophila brain involves pruning of many larval-specific dendrites and axons followed by outgrowth of adult-specific processes. From a genetic mosaic screen, we recovered two independent mutations that block neuronal remodeling in the mushroom bodies (MBs). These phenotypically indistinguishable mutations affect Baboon function, a Drosophila TGF-beta/activin type I receptor, and dSmad2, its downstream transcriptional effector. We also show that Punt and Wit, two type II receptors, act redundantly in this process. In addition, knocking out dActivin around the mid-third instar stage interferes with remodeling. Binding of the insect steroid hormone ecdysone to distinct ecdysone receptor isoforms induces different metamorphic responses in various larval tissues. Interestingly, expression of the ecdysone receptor B1 isoform (EcR-B1) is reduced in activin pathway mutants, and restoring EcR-B1 expression significantly rescues remodeling defects. We conclude that the Drosophila Activin signaling pathway mediates neuronal remodeling in part by regulating EcR-B1 expression.

Screening Healthy Infants for Iron Deficiency Using Reticulocyte Hemoglobin Content

Current clinical practice relies on hemoglobin to detect iron deficiency, which misses infants not yet anemic and places them at higher risk for neurocognitive impairment. Reticulocyte hemoglobin content (CHr) has never been compared with hemoglobin for screening healthy infants.

The Interpreter As Cultural Educator of Residents: Improving Communication for Latino Parents

To determine whether augmentation of the Spanish interpreter's role to include cultural education of residents can improve the satisfaction of Latino patients.

Cost-effectiveness of Omalizumab in Adults with Severe Asthma: Results from the Asthma Policy Model

Omalizumab (trade name Xolair) is approved by the US Food and Drug Administration for treatment of moderate-to-severe allergic asthma. Given the high acquisition cost of omalizumab, its role and cost-effectiveness in disease management require definition.

Racial/Ethnic Variation in Parent Perceptions of Asthma

Black and Latino children with asthma have worse morbidity and receive less controller medication than their white peers. Scant information exists on racial/ethnic differences in parent perceptions of asthma. To compare parent perceptions among black, Latino, and white children with asthma in 4 domains: (1) expectations for functioning with asthma; (2) concerns about medications; (3) interactions with providers; and (4) competing family priorities.

Postpartum Mothers' Attitudes, Knowledge, and Trust Regarding Vaccination

To examine attitudes and knowledge about vaccinations in postpartum mothers.

Repeatability of Response to Asthma Medications

Pharmacogenetic studies of drug response in asthma assume that patients respond consistently to a treatment but that treatment response varies across patients; however, no formal studies have demonstrated this.

Outcomes After Periodic Use of Inhaled Corticosteroids in Children

Many children with persistent asthma use inhaled corticosteroids on a periodic basis. Clinical trials in adults suggest that periodic use of inhaled corticosteroids may be effective for patients with mild persistent asthma. However, scant information exists on the clinical outcomes of children with asthma who are using inhaled corticosteroids on a periodic basis in real-world settings.

Asthma Self-assessment in a Medicaid Population

Self-assessment of symptoms by patients with chronic conditions is an important element of disease management. A recent study in a commercially-insured population found that patients who received automated telephone calls for asthma self-assessment felt they benefitted from the calls. Few studies have evaluated the effectiveness of disease self-assessment in Medicaid populations. The goals of this study were to: (1) assess the feasibility of asthma self-assessment in a population predominantly insured by Medicaid, (2) study whether adding a gift card incentive increased completion of the self-assessment survey, and (3) evaluate how the self-assessment affected processes and outcomes of care.

Predicting Response to Short-acting Bronchodilator Medication Using Bayesian Networks

Bronchodilator response tests measure the effect of beta(2)-agonists, the most commonly used short-acting reliever drugs for asthma. We sought to relate candidate gene SNP data with bronchodilator response and measure the predictive accuracy of a model constructed with genetic variants.

Characterization of Rat Forepaw Function in Two Models of Cervical Dorsal Root Injury

Dorsal root injury (DRI) disrupts afferent input from the periphery and often leads to sensory deficits and neuropathic pain. Despite cervical root injuries in rodents being a useful model for deafferentation studies, a quantitative characterization of the sensory deficits produced by DRI is still lacking. This study aimed to characterize the different functional deficits resulting from a dorsal two- or four-root (C7-C8 and C5-C8, respectively) crush injury in rats at levels that innervate the forepaws. The impairment of the affected forepaw was assessed by mechanical and thermal pain responses, and rating the performance on the skilled reaching and ladder rung walking tests (LRWT). Postoperatively, only the two-root DRI rats developed mechanical allodynia, which persisted throughout the course of the study. Thermal hyperalgesia peaked at weeks 1 and 6. The four-root DRI animals were less sensitive to mechanical and thermal stimulation. Performance on the skilled reaching task could only be measured in two-root DRI rats, as animals with four-root injury were unable to grasp the pellets at all. On the LRWT, gait impairment was proportional to the severity of the lesion, with four-root DRI animals showing a significantly higher rate of errors than two-root DRI animals. These results suggest that two-root DRI represents a good model to assess treatments for allodynia-induced neuropathic pain, and for the restoration of the sensory component of the skilled motor performance. On the other hand, the four-root DRI would be a useful model when forepaw deafferentation is required.

INSIG2 is Associated with Lower Gain in Weight-for-Length Between Birth and Age 6 Months

Researchers have described the association of a common DNA polymorphism, rs7566605, near INSIG2 (insulin-induced gene 2) with obesity in multiple independent populations that include subjects ages 11-60 years.1 To our knowledge, no studies have examined the association of this polymorphism with weight status during early childhood. We explored the association of the rs7566605 polymorphism with weight-for-length among 319 children at 6 months and 3 years participating in Project Viva, a pre-birth cohort study. In contrast to studies of older individuals, CC homozygosity was associated with lower gain in weight-for-length z-score between birth and age 6 months than GG homozygosity or GC heterozygosity. At age 3, we did not find an association. The association of INSIG2 gene with obesity may change direction with age.

Asthma-susceptibility Variants Identified Using Probands in Case-control and Family-based Analyses

Asthma is a chronic respiratory disease whose genetic basis has been explored for over two decades, most recently via genome-wide association studies. We sought to find asthma-susceptibility variants by using probands from a single population in both family-based and case-control association designs.

A Model for Ex Vivo Spinal Cord Segment Culture--a Tool for Analysis of Injury Repair Strategies

Most spinal cord injury research is undertaken using in vivo animal models but the extensive care associated with spinalized animals, inherent variability between animals, and complex surgeries makes alternative models especially valuable. Here we present a novel ex vivo model that enables culture of intact post-natal spinal cord segments for up to five days and the assessment of peripheral nerve grafting repair, enhanced with connexin43 antisense oligodeoxynucleotides (Cx43 AsODN), in this model. Down-regulating Cx43 expression with Cx43 AsODN in cultured spinal cord segments prevents cell death and inhibits inflammation spreading from the site of injury to neighbouring tissue, hence maintaining culture viability. Reduction in segment swelling and improvement in neuron survival were evident after Cx43 AsODN treatment. Furthermore, the combination of Cx43 AsODN with peripheral nerve graft implants into cultured spinal cords promoted axon sprouting from the spinal cord into the peripheral nerve graft. This ex vivo spinal cord segment culture model provides a valuable addition to tools currently available for spinal cord injury research.

Fungal Exposure Modulates the Effect of Polymorphisms of Chitinases on Emergency Department Visits and Hospitalizations

Chitinases are enzymes that cleave chitin, which is present in fungal cells. Two types of human chitinases, chitotriosidase and acidic mammalian chitinase, and the chitinase-like protein, YKL-40, seem to play an important role in asthma. We hypothesized that exposure to environmental fungi may modulate the effect of chitinases in individuals with asthma.

Development of a Pharmacogenetic Predictive Test in Asthma: Proof of Concept

To assess the feasibility of developing a Combined Clinical and Pharmacogenetic Predictive Test, comprised of multiple single nucleotide polymorphisms (SNPs) that is associated with poor bronchodilator response (BDR).

How Can We Communicate About Vaccines with Adolescents and Their Parents?

To describe parents' and adolescents' perceptions about vaccination.

Polymorphisms of Chitinases Are Not Associated with Asthma

Delayed Olfactory Ensheathing Cell Transplants Reduce Nociception After Dorsal Root Injury

Injury to cervical dorsal roots mimics the deafferentation component of brachial plexus injury in humans, with intractable neuropathic pain in the deafferented limb being a common consequence. Such lesions are generally not amenable to surgical repair. The use of olfactory ensheathing cells (OECs) for dorsal root repair, via acute transplantation, has been successful in several studies. From a clinical point of view, delayed transplantation of OECs would provide a more realistic timeframe for repair. In this study we investigated the effect of delayed OEC transplantation on functional recovery of skilled forepaw movements and amelioration of neuropathic pain, using a C7 and C8 dorsal root injury rat model previously established in our lab. We found that OEC transplantation to the dorsal horn 1 week after root injury effectively attenuated neuropathic disturbances associated with dorsal root injury, including spontaneous pain behavior, tactile allodynia and thermal hyperalgesia. The sensory controls of complex, goal-oriented skilled reaching and ladder walking, however, were not improved by delayed OEC transplantation. We did not detect any significant influence of transplanted OECs on injury-induced central reorganisation and afferent sprouting. The anti-nociceptive effect mediated by OEC transplants may therefore be explained by alternative mechanisms such as modification of inflammation and astrogliosis. The significant effect of OEC transplants in mitigating neuropathic pain may be clinically useful in intractable pain syndromes arising from deafferentation. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.

A Preconditioning Nerve Lesion Inhibits Mechanical Pain Hypersensitivity Following Subsequent Neuropathic Injury

A preconditioning stimulus can trigger a neuroprotective phenotype in the nervous system - a preconditioning nerve lesion causes a significant increase in axonal regeneration, and cerebral preconditioning protects against subsequent ischemia. We hypothesized that a preconditioning nerve lesion induces gene/protein modifications, neuronal changes, and immune activation that may affect pain sensation following subsequent nerve injury. We examined whether a preconditioning lesion affects neuropathic pain and neuroinflammation after peripheral nerve injury.

Predictors of Symptoms Are Different from Predictors of Severe Exacerbations from Asthma in Children

Asthma therapy is typically prescribed and titrated based on patient or parent self-report of symptoms. No longitudinal studies have assessed the relationship between symptoms and severe asthma exacerbations in children. The goal of our study was (1) to assess the association of asthma symptoms with severe asthma exacerbations and (2) to compare predictors of persistent asthma symptoms and predictors of severe asthma exacerbations.

Propensity Score-based Sensitivity Analysis Method for Uncontrolled Confounding

The authors developed a sensitivity analysis method to address the issue of uncontrolled confounding in observational studies. In this method, the authors use a 1-dimensional function of the propensity score, which they refer to as the sensitivity function (SF), to quantify the hidden bias due to unmeasured confounders. The propensity score is defined as the conditional probability of being treated given the measured covariates. Then the authors construct SF-corrected inverse-probability-weighted estimators to draw inference on the causal treatment effect. This approach allows analysts to conduct a comprehensive sensitivity analysis in a straightforward manner by varying sensitivity assumptions on both the functional form and the coefficients in the 1-dimensional SF. Furthermore, 1-dimensional continuous functions can be well approximated by low-order polynomial structures (e.g., linear, quadratic). Therefore, even if the imposed SF is practically certain to be incorrect, one can still hope to obtain valuable information on treatment effects by conducting a comprehensive sensitivity analysis using polynomial SFs with varying orders and coefficients. The authors demonstrate the new method by implementing it in an asthma study which evaluates the effect of clinician prescription patterns regarding inhaled corticosteroids for children with persistent asthma on selected clinical outcomes.

Genome Wide Association Study to Predict Severe Asthma Exacerbations in Children Using Random Forests Classifiers

Personalized health-care promises tailored health-care solutions to individual patients based on their genetic background and/or environmental exposure history. To date, disease prediction has been based on a few environmental factors and/or single nucleotide polymorphisms (SNPs), while complex diseases are usually affected by many genetic and environmental factors with each factor contributing a small portion to the outcome. We hypothesized that the use of random forests classifiers to select SNPs would result in an improved predictive model of asthma exacerbations. We tested this hypothesis in a population of childhood asthmatics.

Role of Gap Junctions in Chronic Pain

Gap junctions are specialized transmembrane channels that allow rapid electrical signalling and direct intercellular communication for maintenance and coordination of normal cellular activities and homeostasis. Although gap junction channels in the nervous system mediate intercellular coupling between glial cells and between neurons, they also contribute to the spread of secondary damage and inflammation under pathological conditions. There is now evidence of the involvement of gap junctions in chronic pain caused by nervous system damage or tissue inflammation. In this Mini-Review, we highlight recent studies demonstrating the dynamic plasticity of gap junctions in response to nervous system injury and the effects of gap junction blockade on neuronal survival and modulation of pain in animal models of neuropathic and inflammatory pain. The involvement of dorsal root ganglia and spinal cord gap junctions in mediating chronic pain and the potential for targeting connexins as a novel modality for the treatment of intractable pain syndromes arising from nervous system injury and disorders are discussed.

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