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Il-Ok Lee PhD Ryan A. Whitehead BSc Craig R. Ries MD PhD Stephan K. W. Schwarz MD PhD Ernest Puil PhD Bernard A. MacLeod MD 《Journal canadien d'anesthésie》2013,60(8):780-786
Purpose
Intractable neuropathic dynamic allodynia remains one of the major symptoms of human trigeminal neuropathy and is commonly accepted to be the most excruciatingly painful condition known to humankind. At present, a validated animal model of this disorder is necessary for efficient and effective development of novel drug treatments. Intracisternal strychnine in rats has been shown to result in localized trigeminal dynamic allodynia, thus representing a possible model of trigeminal neuralgia. The purpose of this study was to validate a mouse model of trigeminal glycinergic inhibitory dysfunction using established positive (carbamazepine epoxide) and negative (morphine) controls.Methods
The actions of conventional first-line treatment (carbamazepine epoxide [CBZe]) and clinically ineffective morphine were tested for trigeminal dynamic mechanical allodynia produced by intracisternal strychnine. In mice under halothane anesthesia, we injected either strychnine (0.3 μg), strychnine with CBZe (4 ng), or artificial cerebrospinal fluid (aCSF) intracisternally (i.c.). In a separate set of experiments, subcutaneous morphine (3 mg·kg?1 sc) was injected with intracisternal strychnine. Dynamic mechanical allodynia was induced by stroking the fur with polyethylene (PE-10) tubing. The response of each mouse was rated to determine its allodynia score, and scores of each group were compared. In addition, in a separate dichotomous disequilibrium study, pairs of mice were injected with strychnine/saline, strychnine/strychnine-CBZe, or strychnine/strychnine-morphine. A blinded observer recorded which mouse of each pair had the greater global pain behaviour.Results
Strychnine (i.c.) produced higher quantitative allodynia scores in the trigeminal distribution (mean 81.5%; 95% confidence interval [CI] 76.4 to 86.6) vs the aCSF group (mean 11.3%; 95% CI 8.1 to 14.4) (P < 0.0001). Carbamazepine epoxide (i.c.) completely abolished allodynia when co-injected with strychnine (mean 83.2%; 95% CI 78.1 to 88.4) vs strychnine alone (mean 3.2%; 95% CI ?0.9 to 7.2) (P < 0.0001). Morphine co-injected with strychnine did not result in reduced allodynia (mean 65.7%; 95% CI 42.0 to 89.4) compared with strychnine alone (mean 87.6%; 95% CI 77.6 to 97.6) (P = 0.16). In a further global allodynia assessment, strychnine (i.c.) produced greater allodynia than both aCSF and strychnine administered with CBZe (P = 0.03). Morphine (ip) administered with strychnine did not result in reduced global allodynia compared with strychnine administered alone (P = 1.0).Conclusion
In this study, we have developed and validated a novel murine model of trigeminal dynamic allodynia induced by intracisternal strychnine. The use of mice to study trigeminal allodynia has many benefits, including access to a vast repository of transgenic mouse variants, ease of handling, low cost, and minimal variance of results. The present model may have utility in screening drug treatments for dynamic mechanical allodynia resulting from trigeminal neuropathies. 相似文献65.
L. Luo K. Nishi E. MacLeod M. I. Sabara M. Lin K. Handel J. Pasick 《Transboundary and Emerging Diseases》2013,60(2):143-151
Genes encoding a major structural glycoprotein, E2, of classical swine fever viruses (CSFV) Brescia (subgroup 1.2), Paderborn (subgroup 2.1) and Kanagawa (subgroup 3.4) were constructed by removing the transmembrane domain and adding a C‐terminal 6 histidine (His) tag. All the E2 constructs were efficiently expressed in a baculovirus system as 53‐kDa glycosylated proteins that were identified in Western blots by their reaction with anti‐His and CSFV‐specific antibodies. These proteins were used as ELISA antigens to confirm the existence of an antigenic relationship between the viruses using group‐specific polyclonal antisera. Antigenic differences were identified by Western blot and ELISA reactivity of the E2 proteins with a panel of monoclonal antibodies. Specifically, one monoclonal antibody (WH303) reacted with all three proteins, two monoclonal antibodies (M1660 and M1665) reacted with only the Brescia E2 protein, and three monoclonal antibodies (M1654, M1664 and M1669) reacted equally well with only Brescia and Kanagawa E2 proteins. Therefore, antibody reactivity profiles, established using recombinant E2 proteins, could be used to quickly identify novel CSFV strains as illustrated in this report with only a limited number of monoclonal antibodies. These proteins could also have added utility in the production of monoclonal antibodies and as critical reagents in diagnostic assays. 相似文献
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Catheter-based electrophysiological studies of the epicardium are limited to regions near the coronary vessels or require transthoracic access. We have developed a statistical approach by which to estimate high-resolution maps of epicardial activation from very low-resolution multi-electrode venous catheter measurements. This technique uses a linear estimation model that derives a relationship between venous catheter measurements and unmeasured epicardial sites from a set of previously recorded, high-resolution epicardial activation-time maps used as a training data set based on the spatial covariance of the measurement sites. We performed 14 dog experiments with various interventions to create an epicardial activation-time map database. This database included a total of 592 epicardial activation maps which were recorded using a sock array placed on the ventricles of dog hearts. We present five approaches, which examined sequential addition and removal of maps to select a generalized training set for the estimation technique. The selection consisted of choosing a subset of epicardial ectopic activation-time maps from the database of beats which resulted in estimation accuracy levels better than or at least similar to using all the maps in database. Our aim was to minimize the redundancy in the database and to be able to guide the eventual procedures required to obtain training data from open-chest surgery patients. The results from this study illustrated this redundancy and suggested that by including an optimal subset (around 100 maps) of the full database the estimation technique was able to perform as well as and even in some cases better than including all the maps in the database. The results also suggest that such an approach is feasible for providing accurate reconstruction of complete epicardial activation-time maps in a clinical setting and with fewer maps we can obtain similar reconstruction accuracy levels. 相似文献
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Suzanne Rainsford MBBS FAChPM Roderick D. MacLeod PhD FAChPM Nicholas J. Glasgow MD FAChPM Donna M. Wilson RN PhD Christine B. Phillips MPH FRACGP Robert B. Wiles MBBS FRCGP 《Health & social care in the community》2018,26(3):273-294
The ‘good death’ is one objective of palliative care, with many ‘good death’ viewpoints and research findings reflecting the urban voice. Rural areas are distinct and need special consideration. This scoping review identified and charted current research knowledge on the ‘good’ rural death through the perspectives of rural residents, including rural patients with a life‐limiting illness, to identify evidence and gaps in the literature for future studies. A comprehensive literature search of English language articles (no date filter applied) was conducted in 2016 (2 January to 14 February) using five library databases. Reference lists of included articles, recent issues of eight relevant journals and three grey literature databases were also hand‐searched. Twenty articles (for 17 studies and one systematic review) were identified after a two‐phase screening process by two reviewers, using pre‐determined inclusion criteria. Data from each study were extracted and charted, analysed using a thematic analysis of the included articles' content, and with a quantitative analysis of the scoping review. These papers revealed data collected from rural patients with a life‐limiting illness and family caregivers, rural healthcare providers, the wider rural community, rural community leaders and rural health administrators and policy makers. Rural locations were heterogeneous. Residents from developed and developing countries believe a ‘good death’ is one that is peaceful, free of pain and without suffering; however, this is subjective and priorities are based on personal, cultural, social and religious perspectives. Currently, there is insufficient data to generalise rural residents' perspectives and what it means for them to die well. Given the extreme importance of a ‘good death’, there is a need for further studies to elicit rural patient and family caregiver perspectives. 相似文献
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Interleukin-4 (IL-4) is a potent mediator of growth and differentiation of cells of several hematopoietic lineages. Interleukin-5 (IL-5) is a lineage-specific hematopoietic growth factor that stimulates the production of eosinophils and eosinophil colonies from normal human bone marrow cells. By using somatic cell hybrids and in situ chromosomal hybridization, we localized the IL-4 and IL-5 genes to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the IL-4 and IL-5 genes were found to be deleted in the 5q- chromosome of four patients with refractory anemia (RA) or therapy-related acute nonlymphocytic leukemia (t-ANLL), who had a del(5q). Thus a small segment of chromosome 5 contains IL-4, IL-5, IL- 3, and GM-CSF as well as other genes such as CD14 and EGR1. Our findings that each of these genes was deleted in the 5q- chromosome suggest that loss of function of one or more of these genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q). 相似文献
70.
To define further the role of hemin-controlled repressor (HCR) in globin synthesis, we studied its effect on the synthesis of individual globin chains in a rabbit reticulocyte lysate cell-free system. In the presence of HCR there was a marked globin chain imbalance, resulting in a lowered alpha/beta ratio. These findings in vitro may have relevance to certain clinical heme deficiency states in which a similar globin chain imbalance has been observed. 相似文献