bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Regional and Whole-body Hypothermic Treatment before and after Median Nerve Injury on Neuropathic Pain and Glial Activation in Rat Cuneate Nucleus
Authors: Tsai Yi-Ju , Huang Chun-Ta , Lin Shih-Chang , Yeh Jiann-Horng 
Published: January 2012

Background
Neuroprotective effects of hypothermia on peripheral nerve injury remain uncertain. This study investigated the efficacy of hypothermia in attenuating neuropathic pain and glial activation in the cuneate nucleus in a median nerve chronic constriction injury (CCI) model.

Methods
Sprague-Dawley rats (n = 246) that underwent median nerve ligature at the elbow received various degrees of regional and whole-body hypothermia 15 min before CCI and 5 h, 1, 3, and 5 days after CCI. Hypothermia was maintained for 4 h. Seven days after CCI, behavioral and electrophysiological testings were conducted. Immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analysis of glial activation and measuring pro-inflammatory cytokines, respectively.

Results
Mild (32°C) and deep (28°C) regional hypothermia administered preinjury and 5 h postinjury attenuated neuropathic pain and glial activation. Application of whole-body hypothermia preinjury and 5 h postinjury provided a similar therapeutic effect. However, whole-body hypothermia, but not regional hypothermia, applied 1, 3, and 5 days postinjury attenuated glial activation and neuropathic pain. Similarly, on days 1, 3, and 5 postinjury, only whole-body hypothermia was effective in decreasing proinflammatory cytokine levels. The increase in injury discharge observed after CCI could be suppressed by regional or whole-body hypothermia at different stages of nerve injury.

Conclusions
At the early stage following nerve injury, regional and whole-body hypothermia suppresses ectopic discharges, and consequently inhibits glial activation and neuropathic pain. At the later stage, pain processing is mediated mainly by cytokines released from activated microglia; therefore, only whole-body hypothermia is effective in modulating pain.
First Human Administration of MR04A3
Authors: Sneyd J. Robert , Rigby-Jones Ann E. , Cross Maurice , Tominaga Hideharu , Shimizu Satoshi , Ohkura Takako , Grimsehl Karen 
Published: January 2012

Background
JM-1232(-), (-)-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]-2-phenyl-3,5,6,7-tetrahydrocyclopenta [f]isoindol-1(2H)-one, molecular formula, C(24)H(27)N(3)O(2); molecular weight, 389.49, is a novel isoindoline water-soluble benzodiazepine receptor agonist with favorable anesthetic/sedative properties in animals. MR04A3 is a 1% aqueous presentation of JM-1232(-).

Methods
In Step 1, healthy male volunteers received 10-min infusions of MR04A3, 0.05, 0.1, 0.2, 0.4, and 0.8 mg/kg, with three MR04A3 subjects and one placebo subject per dose concentration. In Step 2, doses were 0.025, 0.05, 0.075, 0.1, 0.2, 0.3, and 0.4 mg/kg over 1 min with six MR04A3 subjects and one placebo subject per dose concentration.

Results
Hypnotic effects of MR04A3 were seen at all dose concentrations in Step 1 and at doses of 0.075 mg/kg or more in Step 2. Central nervous system effect was seen at all dose concentrations with larger doses of MR04A3 producing a deeper and longer reduction in bispectral index. Ramsay sedation scores were increased with higher doses causing sedation and then unresponsiveness. The adverse event profile of subjects receiving MR04A3 was similar to that of subjects given placebo except that some subjects receiving MR04A3 developed upper airway obstruction while sedated. This responded to simple maneuvers (i.e., chin lift). Changes in systolic arterial blood pressure and heart rate were minimal.

Conclusions
MR04A3 is hypnotic in man with a satisfactory hemodynamic and safety profile.
Review article: the pathophysiological roles of the renin–angiotensin system in the gastrointestinal tract
Authors: Garg M. , Angus P. W. , Burrell L. M. , Herath C. , Gibson P. R. , Lubel J. S. 
Published: January 2012

SummaryBackgroundThe renin‐angiotensin system (RAS) is a homeostatic pathway widely known to regulate cardiovascular and renal physiology; however, little is known about its influence in gastrointestinal tissues.AimTo elicit the anatomical distribution and physiological significance of the components of the RAS in the gastrointestinal tract.MethodsAn extensive online literature review including Pubmed and Medline.ResultsThere is evidence for RAS involvement in gastrointestinal physiology and pathophysiology, with all the components required for autonomous regulation identified throughout the gastrointestinal tract. The RAS is implicated in the regulation of glucose, amino acid, fluid and electrolyte absorption and secretion, motility, inflammation, blood flow and possibly malignant disease within the gastrointestinal tract. Animal studies investigating the effects of RAS blockade in a range of conditions including inflammatory bowel disease, functional gut disorders, gastrointestinal malignancy and even intestinal ischaemia have been encouraging to date. Given the ready availability of drugs that modify the RAS and their excellent safety profile, an opportunity exists for investigation of their possible therapeutic role in a variety of human gastrointestinal diseases.ConclusionsThe gastrointestinal renin‐angiotensin system appears to be intricately involved in a number of physiological processes, and provides a possible target for novel investigative and therapeutic approaches.
Imbalance between endothelial injury and repair in patients with polymyalgia rheumatica: improvement with corticosteroid treatment
Authors: Pirro M. , Bocci E. B. , Di Filippo F. , Schillaci G. , Mannarino M. R. , Bagaglia F. , Gerli R. , Mannarino E. 
Published: December 2011

Abstract.  Pirro M, Bocci EB, Di Filippo F, Schillaci G, Mannarino MR, Bagaglia F, Gerli R, Mannarino E (From the Unit of Internal Medicine, Angiology and Arteriosclerosis, Department of Clinical and Experimental Medicine; Division of Rheumatology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy). Imbalance between endothelial injury and repair in patients with polymyalgia rheumatica: improvement with corticosteroid treatment. J Intern Med 2012; 272: 177–184.Objectives.  Polymyalgia rheumatica (PMR) is a rheumatic disease that is characterized by intense activation of systemic inflammation. Systemic inflammation has been associated with an imbalance between endothelial injury and repair, defined by an increased number of circulating endothelial microparticles (EMPs) and a reduced number of endothelial progenitor cells (EPCs). We investigated the association between inflammation and endothelial injury and repair in patients with PMR and evaluated the effects of corticosteroid therapy on EMP and EPC levels.Design, setting and subjects.  We conducted a case–control study in 34 patients with never‐treated active PMR and 34 healthy age‐ and sex‐matched controls. Patients with PMR participated in a 1‐month intervention open‐label study with corticosteroid therapy. Circulating EMPs (CD31+/CD42−) and EPCs (CD34+/KDR+) were quantified by fluorescence‐activated cell sorting analysis.Results.  Patients with PMR had an increased EMP/EPC ratio compared with controls [median (IQR): 6.5 (3.0–11.5) vs. 1.1 (0.7–1.5), P < 0.001], because of both increased EMP and reduced EPC levels. Levels of C‐reactive protein (CRP) were associated with an increased EMP/EPC ratio (β = 0.48, P = 0.001), irrespective of traditional cardiovascular risk factors. Corticosteroid therapy led to a significant CRP reduction [from 3.9 (1.5–6.7) to 0.6 (0.2–1.2) mg dL−1, P < 0.05], paralleled by a consistent 81% decline in the EMP/EPC ratio. CRP and EMP/EPC ratio reductions were significantly correlated (rho = 0.37, P = 0.04).Conclusions.  Polymyalgia rheumatica is associated with a significant imbalance between endothelial injury and repair, which is dependent on the degree of systemic inflammation. Attenuation of inflammation by short‐term corticosteroid therapy might have a role in limiting endothelial fragmentation and promote endothelial repair.
Societal participation: examining the impact of a rehabilitation approach for young people with schizophrenia
Authors: VAN WEL T. F. , LANDSHEER J. A. 
Published: December 2011

Accessible summary
In addition to medical and psychosocial treatment of impairments, societal participation should be recognized as an important treatment goal for patients with schizophrenia, and it can be applied in daily practice by nurses and social workers, even when psychiatric impairments require acute care.
Our research indicated that rehabilitation counselling by nurses and social workers within a multidisciplinary team helps to increase the societal participation level of young people with schizophrenia, while their impairments scores remained stable.
Patients with more mild impairments seemed to profit more from rehabilitation counselling while patients whose impairments were more severe seemed to profit less. Our research also indicated that patients with similar levels of impairment did not show differences in their level of societal participation, regardless of drug use.
Drug use as such is not a contraindication for rehabilitation counselling. Treatment of impairments, including management of drug addiction, should be closely interwoven with support for a patient's rehabilitation goals.
AbstractThis paper is based on research that focuses on the impact of a rehabilitation approach with respect to 99 young people diagnosed with schizophrenia in a Dutch mental health facility. The approach focused on societal participation goals. Nurses and social workers play a key role in such treatment. The research focused on developmental trajectories and showed significant improvement with respect to societal participation levels. Impairment scores remained stable. The results indicate that rehabilitation counselling by nurses and social workers, in addition to medication and psychosocial treatment and integrated in a multidisciplinary team, can make a difference in a patient's societal participation.
Risk factor analysis of hepatitis C virus infection among Chinese blood donors in Hong Kong
Authors: Wong H. K. , Lee C. K. , Leung J. N. S. , Tsoi W. C. , Lin C. K. 
Published: December 2011

Background: Hepatitis C virus (HCV) infection can result in serious hepatic complications and hence potentially significant burden to the society. Despite advances in technology, transfusion‐transmitted HCV infection still exists. To further minimise the risk, a review on the epidemiology of HCV infection among Chinese blood donors in Hong Kong was conducted.Methods: All donations associated with HCV infection confirmed by positive serologic diagnosis with or without molecular confirmation during the period from 2003 to 2010 were studied. Demographic data were retrieved and risk factors were identified.Results: HCV infection was more commonly seen in first time donors and donors with blood transfusion history before the availability of HCV testing, whereas its association with intravenous drug use was noted to be decreasing. Interestingly, half of the HCV positive donors in 2008–2010 were young donors aged below 21, which was also the group with the highest rate of no known source of infection.Conclusion: A subgroup of younger age donors was found to have no known risk factor. To develop better screening strategy, it is recommended that a more detailed analysis of this group of donors is required.
MHC Class II is an Important Genetic Risk Factor for Canine Systemic Lupus Erythematosus (SLE)‐Related Disease: Implications for Reproductive Success
Authors: Wilbe M , Andersson G 
Published: December 2011

ContentsMajor histocompatibility complex (MHC) class II genes are important genetic risk factors for development of immune‐mediated diseases in mammals. Recently, the dog (Canis lupus familiaris) has emerged as a useful model organism to identify critical MHC class II genotypes that contribute to development of these diseases. Therefore, a study aimed to evaluate a potential genetic association between the dog leukocyte antigen (DLA) class II region and an immune‐mediated disease complex in dogs of the Nova Scotia duck tolling retriever breed was performed. We show that DLA is one of several genetic risk factors for this disease complex and that homozygosity of the risk haplotype is disadvantageous. Importantly, the disease is complex and has many genetic risk factors and therefore we cannot provide recommendations for breeders exclusively on the basis of genetic testing for DLA class II genotype.
Investigation on Association and Expression of ESR2 as a Candidate Gene for Boar Sperm Quality and Fertility
Authors: Gunawan A , Cinar MU , Uddin MJ , Kaewmala K , Tesfaye D , Phatsara C , Tholen E , Looft C , Schellander K 
Published: December 2011

ContentsESR2 is involved in oestrogen‐related apoptosis in cell cycle spermatogenesis but their effects have not yet confirmed in pig. Therefore, this study was aimed to investigate the association of ESR2 polymorphism with sperm quality and boar fertility traits and to analyse the ESR2 mRNA and protein expressions in boar reproductive tissues. DNA samples from 203 Pietrain (PI) and 100 Pietrain × Hampshire (PIHA) pigs with records of sperm quality [sperm concentration (SCON), motility (MOT), semen volume (VOL), plasma droplet rate (PDR) and abnormal spermatozoa rate (ASR)] and fertility [non‐return rate (NRR) and number of piglet born alive (NBA)] traits were available. A SNP in coding region of ESR2 g.35547A>G in exon 5 was associated with MOT and PDR in the PI and with SCON, VOL, MOT and PDR in PIHA population. For mRNA and protein expression study, a total of six boars were divided into two groups with group I (G‐I) and group II (G‐II) where G‐I characterized for relatively a better sperm quality according to the mean of two groups. mRNA expression was higher in brain and testis than that in all parts of epididymis. Both qRT‐PCR and western blot analysis revealed that the ESR2 gene expression and protein expression were significantly higher in testis collected from G‐II compared with that of G‐I boars. Moreover, ESR2 protein localization in germ cell, Leydig and Sertoli cells, epithelial cells and spermatozoa was remarkable, which indicated the important role of ESR2 in spermatogenesis process. These results might shed new light on the roles of ESR2 in spermatogenesis as candidate for boar fertility, but still the lack of association across populations should be considered.
Incursion preparedness: anticipating the arrival of an economically important plant pathogen Xylella fastidiosa Wells (Proteobacteria: Xanthomonadaceae) and the insect vector Homalodisca vitripennis (Germar) (Hemiptera: Cicadellidae) in Australia
Authors: Rathé Anna A , Pilkington Leigh J , Gurr Geoff M , Hoddle Mark S , Daugherty Matthew P , Constable Fiona E , Luck Joanne E , Powell Kevin S , Fletcher Murray J , Edwards Owain R 
Published: December 2011

AbstractThe glassy‐winged sharpshooter, Homalodisca vitripennis (Germar) (Hemiptera: Cicadellidae), is an important insect vector of the xylem‐limited plant pathogen Xylella fastidiosa Wells et al. that causes diseases in numerous plant species including food and feedstock crops, ornamentals and weeds. Both the pathogen and the vector are native to the Americas, and H. vitripennis has demonstrated high invasive ability but to date neither has been detected in Australia. The Australian wine grape, table grape, peach, plum, nectarine and citrus industries are particularly concerned about the arrival of X. fastidiosa and H. vitripennis because of the potential economic impact on these important commodities. Other commodity producers in Australia should also be concerned about this vector‐pathogen, in particular the ornamental plant, avocado and olive industries. Past interceptions of H. vitripennis and the potential for X. fastidiosa to be moved in live plant material or within live vectors indicate the need for rapid detection of an incursion in areas considered at high risk. This requires identification of regions that have climatic and environmental conditions conducive to X. fastidiosa and H. vitripennis establishment as well as a detailed knowledge of their respective potential host plant ranges in new areas. These climatic regions and host plant species can then be targeted for monitoring in order to detect an incursion at an early stage. CLIMEX modelling has shown that much of coastal Australia has temperatures suitable for survival of both the vector and pathogen. A range of other requirements in addition to suitable climate must, however, be satisfied for an incursion to lead to establishment, proliferation and spread. This review article provides information that shows that the Australian environment is suitable for the establishment of H. vitripennis and that Australian native plant species are likely to serve as X. fastidiosa hosts and subsequent pathogen sources, and highlights future research directions.
Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin
Authors: Devineni D. , Morrow L. , Hompesch M. , Skee D. , Vandebosch A. , Murphy J. , Ways K. , Schwartz S. 
Published: January 2012

Aim: Canagliflozin is a sodium‐glucose co‐transporter 2 (SGLT2) inhibitor that is being investigated for the treatment of type 2 diabetes mellitus (T2DM).Methods: This was a randomized, double‐blind, placebo‐controlled, parallel‐group, 28‐day study conducted at two sites, in 29 subjects with T2DM not optimally controlled on insulin and up to one oral antihyperglycaemic agent. Subjects were treated with canagliflozin 100 mg QD or 300 mg twice daily (BID) or placebo. Safety, tolerability, pharmacokinetic characteristics and pharmacodynamic effects of canagliflozin were examined. Glucose malabsorption following a 75‐g oral glucose challenge was also examined.Results: Canagliflozin pharmacokinetics were dose‐dependent, and the elimination half‐life ranged from 12 to 15 h. After 28 days, the renal threshold for glucose excretion was reduced; urinary glucose excretion was increased; and A1C, fasting plasma glucose and body weight decreased in subjects administered canagliflozin (A1C reductions: 0.19% with placebo, 0.73% with 100 mg QD, 0.92% with 300 mg BID; body weight changes: 0.03 kg increase with placebo, 0.73 kg reduction with 100 mg QD, 1.19 kg reduction with 300 mg BID). Glucose malabsorption was not observed with canagliflozin treatment. There were no deaths, serious adverse events or severe hypoglycaemic episodes. The incidence of adverse events was similar across groups. There were no clinically meaningful changes in routine laboratory safety tests, vital signs or electrocardiograms.Conclusion: In subjects receiving insulin and oral antihyperglycaemic therapy, canagliflozin was well tolerated without evidence for glucose malabsorption, had pharmacokinetic characteristics consistent with once‐daily dosing, and improved glycaemic control.
Efficacy and safety of suberoylanilide hydroxamic acid (Vorinostat) in the treatment of canine corneal fibrosis
Authors: Bosiack Ann P. , Giuliano Elizabeth A. , Gupta Rangan , Mohan Rajiv R. 
Published: December 2011

AbstractObjective  Study aims were to evaluate the safety and efficacy of the Food and Drug Administration‐approved drug Vorinostat [suberoylanilide hydroxamic acid (SAHA)] in the treatment of canine corneal fibrosis using an in vitro model.Methods  Healthy donor canine corneas were collected and used to generate primary canine corneal fibroblasts (CCFs) by growing cultures in minimal essential medium supplemented with 10% fetal bovine serum. Canine corneal myofibroblasts, used as a model for corneal fibrosis, were produced by growing CCF cultures in serum‐free medium containing transforming growth factor β1 (1 ng/mL). Trypan blue exclusion assays were used to determine the optimal SAHA dose for this in vitro model. Four hour after culturing with TGFβ1, CCF cultures were treated with 0.06% SAHA for 5 min (group 1) and for 24 h (group 2), representing single and multiple dose treatment regimes, respectively. Cultures were then further incubated in the presence of TGFβ1 (1 ng/μL) under serum‐free conditions until they reached 70% confluence. Trypan blue exclusion, immunocytochemistry, and TUNEL assays were used to evaluate the cytotoxicity of SAHA. Real‐time PCR, western blot analysis, and immunocytochemistry were used to determine the efficacy of SAHA to inhibit canine corneal myofibroblast formation.Results  Topical SAHA application in both treatment groups successfully decreased α‐smooth muscle actin expression when compared to the TGFβ1 only treatment group (P < 0.05). Tested SAHA did not affect CCF phenotype or cellular viability and did not cause significant cell death.Conclusions  Suberoylanilide hydroxamic acid safely and effectively inhibits TGFβ1‐induced CCFs transformation to myofibroblast in vitro.
Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in 25 Cavalier King Charles spaniel dogs – part I: clinical signs, histopathology, and inheritance
Authors: Hartley Claudia , Donaldson David , Smith Ken C. , Henley William , Lewis Tom W. , Blott Sarah , Mellersh Cathryn , Barnett Keith C. 
Published: December 2011

AbstractThe clinical presentation and progression (over 9 months to 13 years) of congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID) in the Cavalier King Charles spaniel dog are described for six new cases and six previously described cases. Cases presented with a congenitally abnormal (rough/curly) coat and signs of KCS from eyelid opening. Persistent scale along the dorsal spine and flanks with a harsh frizzy and alopecic coat was evident in the first few months of life. Ventral abdominal skin was hyperpigmented and hyperkeratinized in adulthood. Footpads were hyperkeratinized from young adulthood with nail growth abnormalities and intermittent sloughing. Long‐term follow‐up of cases (13/25) is described. Immunomodulatory/lacrimostimulant treatment had no statistically significant effect on Schirmer tear test results, although subjectively, this treatment reduced progression of the keratitis. Histopathological analysis of samples (skin/footpads/lacrimal glands/salivary glands) for three new cases was consistent with an ichthyosiform dermatosis, with no pathology of the salivary or lacrimal glands identified histologically. Pedigree analysis suggests the syndrome is inherited by an autosomal recessive mode.