急性骨骼肌损伤动物实验模型构建及应用

目的:探讨动物实验模型在急性骨骼肌损伤研究中的应用,为研究骨骼肌损伤机制,了解与认识其病理、病变及转归,探讨预防、治疗及康复措施等提供理论依据和实验基础。资料来源:应用计算机检索HighWire Press、PubMed数据库1986-01/2007-05相关急性骨骼肌损伤动物实验模型方面的文献,检索词"muscular injury,Eccentric Exercise,animal experimental model",限定文献语言种类为English。同时计算机检索CNKI学术期刊1986-01/2006-12相关急性骨骼肌损伤动物实验模型方面的文献,检索词"骨骼肌损伤,动物实验模型",限定文献语言种类为中文。资料选择:对资料进行初审,选取包括急性骨骼肌损伤动物实验模型的文献,开始查找全文。纳入标准:反映骨骼肌拉伸实验、电刺激、下坡跑、钝挫伤及缺血再灌注等方面损伤模型的文章。排除标准:骨骼肌的药物损伤及神经系统人为损伤对肌肉影响实验模型的文章。资料提炼:共检索到64篇关于急性骨骼肌损伤动物实验模型的文献,最终纳入50篇符合标准的文献。资料综合:在骨骼肌损伤的研究中,建立或复制动物损伤模型常常是研究过程中的一个重要环节,其模型的适用性、可靠性和可行性直接关系到实验结果的科学性。有关骨骼肌损伤的实验研究,早期主要侧重于骨骼肌的疾病研究,故实验性动物模型多采用物理、化学及生物学等损伤因子,对骨骼肌直接实施损伤,以此模拟并研究一些骨骼肌疾病的病理过程。近年来,随着体育事业的发展和人们对健康认识的提高,人们对骨骼肌运动性损伤的研究也越来越多。目前,常见的急性骨骼肌损伤模型有肌肉拉伸实验模型、电刺激损伤模型、下坡跑骨骼肌损伤模型、骨骼肌钝挫伤模型、缺血再灌注损伤模型等,这些模型的制作为急性骨骼肌损伤的研究奠定了实验基础。总结己有研究的动物模型,分析其特点和适用性,可对骨骼肌损伤的研究提供重要的实验基础。结论:骨骼肌急性损伤的实质是肌肉组织承受过度载荷所致,而动物实验模型是建立在这一基本理论得以实施的。动物实验模型可复制出骨骼肌急性损伤的典型病理变化,对深入骨骼肌损伤的实验研究具有重要的现实意义。     

Post-traumatic tension faecopneumothorax in a young male: case report

Diaphragmatic rupture due to trauma is both well recognised and uncommon. The difficulties in diagnosing traumatic diaphragmatic rupture at the first admission are the most common causes of latent morbidity and mortality. Herniation of the abdominal viscera is the most common sequel with strangulation and perforation the most serious complication. This case outlines the delayed presentation of diaphragmatic rupture and herniation presenting as an acute tension faecopneumothorax. We review the relevant literature, with particular emphasis on the difficulties in diagnosis at presentation.     

Contemporary management of drug-packers

Experience with management of drug-packers (mules) is variable among different centres. However, despite a recorded increase in drug trafficking in general, as yet, no unified, clear guidelines exist to guide the medical management of those who only occasionally encounter these individuals. We describe our recent experience with this growing problem and discuss the most salient points concerning the contemporary management of body packers. Our recent experience demonstrates that type IV packages may now be managed conservatively for the most part.     

Neglected dorsal dislocation of the scaphoid

Isolated dislocation of the scaphoid is very rare. A 45-year old male, industrial worker reported two and half months after injury with wrist pain and swelling on the dorsum of left wrist. He was diagnosed as neglected dorsal dislocation of scaphoid. Proximal row carpectomy with capsular interposition was done stabilizing the distal carpus on the radius using Kirschner wires. At-12 months follow-up the patient had good wrist function and was satisfied with the outcome of the treatment. We hereby report this neglected dorsal dislocation of scaphoid in view of rarity and discuss the various options for management.     

The Uniform grading tooL for flexIble ureterorenoscoPes (TULIP-tool): a Delphi consensus project on standardised evaluation of flexible ureterorenoscopes

Objective

To develop a standardised tool to evaluate flexible ureterorenoscopes (fURS).

Materials and Methods

A three-stage consensus building approach based on the modified Delphi technique was performed under guidance of a steering group. First, scope- and user-related parameters used to evaluate fURS were identified through a systematic scoping review. Then, the main categories and subcategories were defined, and the expert panel was selected. Finally, a two-step modified Delphi consensus project was conducted to firstly obtain consensus on the relevance and exact definition of each (sub)category necessary to evaluate fURS, and secondly on the evaluation method (setting, used tools and unit of outcome) of those (sub)categories. Consensus was reached at a predefined threshold of 80% high agreement.

Results

The panel consisted of 30 experts in the field of endourology. The first step of the modified Delphi consensus project consisted of two questionnaires with a response rate of 97% (n = 29) for both. Consensus was reached for the relevance and definition of six main categories and 12 subcategories. The second step consisted of three questionnaires (response rate of 90%, 97% and 100%, respectively). Consensus was reached on the method of measurement for all (sub)categories.

Conclusion

This modified Delphi consensus project reached consensus on a standardised grading tool for the evaluation of fURS – The Uniform grading tooL for flexIble ureterorenoscoPes (TULIP) tool. This is a first step in creating uniformity in this field of research to facilitate future comparison of outcomes of the functionality and handling of fURS.     

The value of magnetic resonance imaging and ultrasonography (MRI/US)‐fusion biopsy platforms in prostate cancer detection: a systematic review

Despite limitations considering the presence, staging and aggressiveness of prostate cancer, ultrasonography (US)‐guided systematic biopsies (SBs) are still the ‘gold standard’ for the diagnosis of prostate cancer. Recently, promising results have been published for targeted prostate biopsies (TBs) using magnetic resonance imaging (MRI) and ultrasonography (MRI/US)‐fusion platforms. Different platforms are USA Food and Drug Administration registered and have, mostly subjective, strengths and weaknesses. To our knowledge, no systematic review exists that objectively compares prostate cancer detection rates between the different platforms available. To assess the value of the different MRI/US‐fusion platforms in prostate cancer detection, we compared platform‐guided TB with SB, and other ways of MRI TB (cognitive fusion or in‐bore MR fusion). We performed a systematic review of well‐designed prospective randomised and non‐randomised trials in the English language published between 1 January 2004 and 17 February 2015, using PubMed, Embase and Cochrane Library databases. Search terms included: ‘prostate cancer’, ‘MR/ultrasound(US) fusion’ and ‘targeted biopsies’. Extraction of articles was performed by two authors (M.G. and A.A.) and were evaluated by the other authors. Randomised and non‐randomised prospective clinical trials comparing TB using MRI/US‐fusion platforms and SB, or other ways of TB (cognitive fusion or MR in‐bore fusion) were included. In all, 11 of 1865 studies met the inclusion criteria, involving seven different fusion platforms and 2626 patients: 1119 biopsy naïve, 1433 with prior negative biopsy, 50 not mentioned (either biopsy naïve or with prior negative biopsy) and 24 on active surveillance (who were disregarded). The Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool was used to assess the quality of included articles. No clear advantage of MRI/US fusion‐guided TBs was seen for cancer detection rates (CDRs) of all prostate cancers. However, MRI/US fusion‐guided TBs tended to give higher CDRs for clinically significant prostate cancers in our analysis. Important limitations of the present systematic review include: the limited number of included studies, lack of a general definition of ‘clinically significant’ prostate cancer, the heterogeneous study population, and a reference test with low sensitivity and specificity. Today, a limited number of prospective studies have reported the CDRs of fusion platforms. Although MRI/US‐fusion TB has proved its value in men with prior negative biopsies, general use of this technique in diagnosing prostate cancer should only be performed after critical consideration. Before bringing MRI/US fusion‐guided TB in to general practice, there is a need for more prospective studies on prostate cancer diagnosis.     

Increased endothelin-1 reactivity and endothelial dysfunction in carotid arteries from rats with hyperhomocysteinemia

Background and purpose:

There are interactions between endothelin-1 (ET-1) and endothelial vascular injury in hyperhomocysteinemia (HHcy), but the underlying mechanisms are poorly understood. Here we evaluated the effects of HHcy on the endothelin system in rat carotid arteries.

Experimental approach:

Vascular reactivity to ET-1 and ET_A and ET_B receptor antagonists was assessed in rings of carotid arteries from normal rats and those with HHcy. ET_A and ET_B receptor expression was assessed by mRNA (RT-PCR), immunohistochemistry and binding of [¹²⁵I]-ET-1.

Key results:

HHcy enhanced ET-1-induced contractions of carotid rings with intact endothelium. Selective antagonism of ET_A or ET_B receptors produced concentration-dependent rightward displacements of ET-1 concentration response curves. Antagonism of ET_A but not of ET_B receptors abolished enhancement in HHcy tissues. ET_A and ET_B receptor gene expressions were not up-regulated. ET_A receptor expression in the arterial media was higher in HHcy arteries. Contractions to big ET-1 served as indicators of endothelin-converting enzyme activity, which was decreased by HHcy, without reduction of ET-1 levels. ET-1-induced Rho-kinase activity, calcium release and influx were increased by HHcy. Pre-treatment with indomethacin reversed enhanced responses to ET-1 in HHcy tissues, which were reduced also by a thromboxane A₂ receptor antagonist. Induced relaxation was reduced by BQ788, absent in endothelium-denuded arteries and was decreased in HHcy due to reduced bioavailability of NO.

Conclusions and implications:

Increased ET_A receptor density plays a fundamental role in endothelial injury induced by HHcy. ET-1 activation of ET_A receptors in HHcy changed the balance between endothelium-derived relaxing and contracting factors, favouring enhanced contractility.British Journal of Pharmacology (2009) 157, 568–580; doi:10.1111/j.1476-5381.2009.00165.x; published online 9 April 2009This article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

Efficacy of 3,5-dibromo-L-phenylalanine in rat models of stroke,seizures and sensorimotor gating deficit

Background and purpose:

Abnormal glutamatergic activity is implicated in neurologic and neuropsychiatric disorders. Selective glutamate receptor antagonists were highly effective in animal models of stroke and seizures but failed in further clinical development because of serious side effects, including an almost complete set of symptoms of schizophrenia. Therefore, the novel polyvalent glutamatergic agent 3,5-dibromo-L-phenylalanine (3,5-DBr-L-Phe) was studied in rat models of stroke, seizures and sensorimotor gating deficit.

Experimental approach:

3,5-DBr-L-Phe was administered intraperitoneally as three boluses after intracerebral injection of endothelin-1 (ET-1) adjacent to the middle cerebral artery to cause brain injury (a model of stroke). 3,5-DBr-L-Phe was also given as a single bolus prior to pentylenetetrazole (PTZ) injection to induce seizures or prior to the administration of the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) to cause disruption of prepulse inhibition (PPI) of startle (sensorimotor gating deficit).

Key results:

Brain damage caused by ET-1 was reduced by 52%, which is comparable with the effects of MK-801 in this model as reported by others. 3,5-DBr-L-Phe significantly reduced seizures induced by PTZ without the significant effects on arterial blood pressure and heart rate normally caused by NMDA antagonists. 3,5-DBr-L-Phe prevented the disruption of PPI measured 3 days after the administration of ET-1. 3,5-DBr-L-Phe also eliminated sensorimotor gating deficit caused by MK-801.

Conclusion and implications:

The pharmacological profile of 3,5-DBr-L-Phe might be beneficial not only for developing a therapy for the neurological and cognitive symptoms of stroke and seizures but also for some neuropsychiatric disorders.