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Unrestricted Weight Bearing as a Method for Assessment of Nociceptive Behavior in a Model of tibiofemoral Osteoarthritis in Rats

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Journal of Behavioral and Brain Science 2013年第3期3卷 306-314页

作者： Lise Skott Gregersen turid Rosland Lars Arendt-Nielsen garth whiteside Michele Hummel Center for Sensory-Motor Interaction Aalborg UniversityAalborgODenmark Purdue Pharma LP CranburyUSA

Background: Novel preclinical models for prediction of osteoarthritis-like pain are necessary for the elucidation of osteoarthritis (OA) pathology and for assessment of novel analgesics. A widely used behavioral test in rat models of tibiofemoral OA is hind limb weight bearing (WB). However, this method evaluates WB in an unnaturally restricted manner. the aim of this study was therefore to characterize the tekscan Pressure Measurement System as a means to assess OA-like tibiofemoral pain in rats by determination of plantar pressure distribution in a more natural and unrestricted position, defined as unrestricted WB. Methods: Intra-articular injections of 1 mg monosodium iodoacetate (MIA) or saline were administrated in the left hind knee of 84 male Sprague Dawley rats. Changes in unrestricted WB between ipsilateral and contralateral hindlimbs were determined. Morphine (5 mg/kg administered subcutaneously) and naproxen (60 mg/kg per-oral) were examined for their ability to reverse WB changes. Results: Changes in hind limb unrestricted WB were observed 14 (P P P Conclusion: this study indicated that unrestricted WB assessed by the tekscan system can be utilized as a clinically relevant method to assess aberrations in WB induced by intra-articular MIA injections in rodents. therefore, this system may be useful for understanding the mechanisms of OA pain in humans and may also assist in the discovery of novel pharmacological agents.

关键词： Osteoarthritis Pain Monosodium Iodoacetate Unrestricted Weight Bearing Morphine Naproxen

treatment of Peripheral Neuropathy: Combination therapy Using LED Light, Extracorporeal Shockwave therapy, Platelet Rich Plasma, and an Oral Dietary Supplement

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International Journal of Clinical Medicine 2023年第5期14卷 250-259页

作者： Alex Spinoso Robert Settineri Christine McLaren garth L. Nicolson Elite Medical Corona CA USA Sierra Productions Research Irvine California USA Department of Medicine University of California Irvine Irvine CA USA Institute for Molecular Medicine Huntington Beach CA USA

Objectives: Peripheral neuropathy (PN) is a significant contributor to disability in the elderly. It is also one of the most prevalent complications of type 2 diabetes, prediabetes and metabolic syndrome. PN is commonly associated with pain, numbness, tingling, burning, and cramping in the feet and legs. Current treatment options are limited to controlling pain, seizures and use of antidepressant medications. these treatments have undesirable side effects and don’t stop PN progression. Here we utilized a combination of individual-specific modalities to improve local circulation and relieve PN symptoms. Methods: We conducted an open-label, multicenter pilot trial with 34 subjects (19 males and 15 females ranging from 40 - 85 years of age). All of the participants were diagnosed with peripheral neuropathy and had bilateral symptoms in their feet, and many reported the same symptoms (pain, numbness, tingling, burning, and cramping) in their lower legs. the duration of symptoms ranged from four months to over six years. On Day 0, subjects were given a 90-day supply of the oral supplement with dosing instructions and a LED light therapy device. they also received three platelet-rich plasma (PRP) injections in their lower extremities. Subjects also received an extracorporeal shockwave therapy (ESWt) treatment for each foot and subsequently twice per week for the first six weeks, then once weekly for the duration of the study. Subjects filled out the Brief Pain Index (BPI) at weekly intervals. On Day 90, subjects completed the Patient Global Impression of Change (PGIC) survey. Results: there were significant responses to pain, as evidenced by BPI scores at weeks 8, 9, 10 and 11 (p = 0.02, 0.01, 0.02, and 0.003, respectively). Analysis of the final day PGIC survey showed a favorable outcome for 73% of participants (p = 0.003), with the majority reporting Very Much Improved. Conclusions: By utilizing a multi-modality treatment protocol that includes PRP, LED light therapy, E

关键词： Peripheral Neuropathy LED Light therapy Device Extracorporeal Shockwave therapy PRP Injections Oral Supplement Multi-Modality treatment Pain

B7-H4 as a protective shield for pancreatic islet beta cells

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World Journal of Diabetes 2014年第6期5卷 739-746页

作者： Annika C Sun Dawei Ou Dan S Luciani garth L Warnock Department of Surgery University of British Columbia

Auto- and alloreactive t cells are major culprits that damage β-cells in type 1 diabetes(t1D) and islet transplantation. Current immunosuppressive drugs can alleviate immune-mediated attacks on islets. t cell co-stimulation blockade has shown great promise in autoimmunity and transplantation as it solely targets activated t cells, and therefore avoids toxicity of current immunosuppressive drugs. An attractive approach is offered by the newly-identified negative t cell cosignaling molecule B7-H4 which is expressed in normal human islets, and its expression co-localizes with insulin. A concomitant decrease in B7-H4/insulin colocalization is observed in human type 1 diabetic islets. B7-H4 may play protective roles in the pancreatic islets, preserving their function and survival. In this review we outline the protective effect of B7-H4 in the contexts of t1 D, islet cell transplantation, and potentially type 2 diabetes. Current evidence offers encouraging data regarding the role of B7-H4 in reversal of autoimmune diabetes and donor-specific islet allograft tolerance. Additionally, unique expression of B7-H4 may serve as a potential biomarker for the development of t1 D. Futurestudies should continue to focus on the islet-specific effects of B7-H4 with emphasis on mechanistic pathways in order to promote B7-H4 as a potential therapy and cure for t1 D.

关键词： Diabetes mellitus Autoimmunity transplantation Co-stimulation blockade Biomarker

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出奇制胜——存储过程中的错误处理

程序员（CSDN开发高手） 2004年第7期 81-83页

作者： garth 朱莹莹

本文介绍了在存储过程中处理错误的一些基本方法。如果你还不清楚致命错误和非致命错误之间的区别、系绕函数@@ERROR(返回执行的最后一条transact-SQL语句的错误编号)、或不知道如何用系统存储过程sp_addmessage添加定制错误消息，那么... 详细信息

本文介绍了在存储过程中处理错误的一些基本方法。如果你还不清楚致命错误和非致命错误之间的区别、系绕函数@@ERROR(返回执行的最后一条transact-SQL语句的错误编号)、或不知道如何用系统存储过程sp_addmessage添加定制错误消息，那么你会发现这篇文章非常有趣。

关键词：存储过程错误处理 t-SQL 定制消息系统添加出奇制胜执行编号

Role of ion channels in gastrointestinal cancer

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World Journal of Gastroenterology 2019年第38期25卷 5732-5772页

作者： Kyle J Anderson Robert t Cormier Patricia M Scott Department of Biomedical Sciences University of Minnesota Medical School

In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer *** functions of ion channels in the gastrointestinal(GI)tract influence a variety of cellular processes,many of which overlap with these hallmarks of *** this review we focus on the roles of the calcium(Ca^2+),sodium(Na^+),potassium(K^+),chloride(Cl^-)and zinc(Zn^2+)transporters in GI cancer,with a special emphasis on the roles of the KCNQ1 K+channel and CFtR Cl-channel in colorectal cancer(CRC).Ca^2+is a ubiquitous second messenger,serving as a signaling molecule for a variety of cellular processes such as control of the cell cycle,apoptosis,and *** members of the tRP superfamily,including tRPM8,tRPM7,tRPM6 and tRPM2,have been implicated in GI cancers,especially through overexpression in pancreatic adenocarcinomas and down-regulation in colon ***-gated sodium channels(VGSCs)are classically associated with the initiation and conduction of action potentials in electrically excitable cells such as neurons and muscle *** VGSC NaV1.5 is abundantly expressed in human colorectal CRC cell lines as well as being highly expressed in primary CRC *** have demonstrated that conductance through NaV1.5 contributes significantly to CRC cell invasiveness and cancer ***2+transporters of the ZIP/SLC39A and Znt/SLC30A families are dysregulated in all major GI organ cancers,in particular,ZIP4 up-regulation in pancreatic cancer(PC).More than 70 K+channel genes,clustered in four families,are found expressed in the GI tract,where they regulate a range of cellular processes,including gastrin secretion in the stomach and anion secretion and fluid balance in the intestinal *** distinct types of K+channels are found dysregulated in the GI *** are hERG1 upregulation in PC,gastric cancer(GC)and CRC,leading to enhanced cancer angiogenesis and invasion,and KCNQ1 down-regulation in CR

关键词： Ion channels Gastrointestinal cancer Colorectal cancer Gastric cancer Pancreatic cancer Esophageal cancer Hepatocellular carcinoma Prognostic biomarker Novel therapies Clinical targets

IRX-2, a novel biologic, favors the expansion of t effector over t regulatory cells in a human tumor microenvironment model

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世界最新医学信息文摘 2015年第5期 8-8页

作者： Bastian Schilling Malgorzata Harasymczuk Patrick Schuler James E.Egan theresa L.whiteside

IRX-2, a natural cytokine biological with multiple components, has been used in preclinical and clinical studies to promote antitumor activity of t lymphocytes. to define cellular mechanisms responsible for antitumor effects of IRX-2, its ability to induce effector t cells( teff) was examined in a model simulating the tumor microenvironment. An in vitro model containing conventional CD4+CD25 cells co-cultured with autologous immature dendritic cells, irradiated tumor cells, and cytokines was used to study differentiation and expansion of regulatory t cells(treg) and teff in the presence and absence of IRX-2. Phenotype, suppressor function, signaling, and cytokine production were serially measured using flow cytometry, Western blots, CFSE-based suppressor assays, and Luminex-based analyses. the presence of IRX-2 in the co-cultures promoted the induction and expansion of IFN- +tbet+ teff and significantly(pthe induction of inducible IL-10+tGF-β+treg. the responsible mechanism involved IFN-+-driven t cell polarization towards teff and suppression of treg *** an in vitro model simulating the human tumor microenvironment, IRX-2 promoted teff expansion and antitumor activity without inducing treg. thus, IRX-2 could be considered as a promising component of future antitumor therapies.

关键词： IRX-2 Immunomodulator treg teff tumor microenvironment Cytokines t helper cells Cancer im-munotherapy

针对转移大白鼠乳腺癌细胞表面抗原的单克隆抗体的特性鉴定

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细胞与分子免疫学杂志 1986年第Z1期 27-27页

作者： Susan M.North garth L.Nicolson 郭明 Department of tumor Biology(108) U. t-M. D. Anderson Hospital and tumor institufe 77030 Department of tumor Biology(108) U. t-M. D. Anderson Hospital and tumor institufe 77030

作者已获得一种针对13762NF大白鼠腺癌的转移克隆株(MtLn3)所表达的细胞表面面抗原的单克隆抗体,这种McAb是用二种不同的免疫方案获得的。第一个方案是把一个携带同系肿瘤(MtLn3)21天的供体脾细胞与小鼠骨髓瘤细胞的Y3 Ag,1、2、3相融... 详细信息

作者已获得一种针对13762NF大白鼠腺癌的转移克隆株(MtLn3)所表达的细胞表面面抗原的单克隆抗体,这种McAb是用二种不同的免疫方案获得的。第一个方案是把一个携带同系肿瘤(MtLn3)21天的供体脾细胞与小鼠骨髓瘤细胞的Y3 Ag,1、2、3相融合。用这一方法分离出许多产生抗体的克隆株。第二种方案采用的脾细胞来源于接受一种不完全提纯的粘蛋白样表面糖蛋白(gp580)反复免疫的小鼠,在13762NF小鼠中gp580的表达已被证

关键词：表面抗原细胞表面单克隆抗体细胞大白鼠家鼠属

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自由振荡能触发可预测地震的前震吗?

世界地震译丛 2000年第2期31卷 32-36页

作者： S.W.Costello t.E.tullis 郭贵安广东省地震局

检验了whiteside和Ben-Zion(1995)提出的地震预测模型,确定该方法是否能得到统计意义上的结果。他们的模型提出,在主震之前数月,由于地球自由振荡的作用,在主震区附近会引发大量小震。我们独立地编制了一种程序来重现他们的方法。结果发... 详细信息

检验了whiteside和Ben-Zion(1995)提出的地震预测模型,确定该方法是否能得到统计意义上的结果。他们的模型提出,在主震之前数月,由于地球自由振荡的作用,在主震区附近会引发大量小震。我们独立地编制了一种程序来重现他们的方法。结果发现,他们所采用的方法依赖于计算触发百分比的事件数目。研究结果表明,用真实数据和随机数据得到的结果没什么差别。同时还提出用一个参数去消除采样偏差和检验零假设。这个假设的要点是用真实数据得到的结果与随机碰上的结果没有差别。这一假设在我们的研究中得到了证实,我们的结果还发现洛马普列塔主震之前,触发参数没有明显增大。

关键词：地震预测自由振荡能前震