bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous infusion of the cannabinoid WIN 55,212–2 to the site of a peripheral nerve injury reduces mechanical and cold hypersensitivity
Authors: Lever I J , Pheby T M , Rice A S C 
Published: March 2007

Background and purpose:Cannabinoids have analgesic and anti‐inflammatory properties but their use is limited by psychotropic activity at CNS receptors. Restricting cannabinoid delivery to peripheral tissues at systemically inactive doses offers a potential solution to this problem.Experimental approach:WIN 55,212‐2 was continuously delivered to the site of a partial ligation injury to the sciatic nerve via a perineural catheter connected to a mini‐osmotic pump implanted at the time of injury. Bilateral reflex limb withdrawal behaviour was measured in adult male Wistar rats in response to mechanical and cooling stimulation of the hind paw.Key results:Compared with vehicle treatment, WIN 55,212‐2 (1.4μg μl−1 hr−1) reduced hypersensitivity to stimuli applied to the injured limb at 2, 4 and 6 days after injury. The effects of WIN 55,212‐2 (0.6‐2.8μg μl−1 hr−1) were dose‐dependent. Estimated EC50 values for reduction in mean responses to mechanical and cooling stimulation (day 4 post‐surgery) were 1.55 (95% C.I, [1.11‐2.16]) μg μl−1 hr−1 and 1.52 (95% C.I, [1.07‐2.18]) μg μl−1 hr−1, respectively. When delivered to the contralateral side to injury, WIN 55,212‐2 (1.4 or 2.8μg μl−1 hr−1) did not significantly affect nerve injury‐associated hypersensitivity. Co‐perineural application of a CB1 receptor antagonist SR141716a and WIN 55,212‐2 prevented the effects of WIN 55,212‐2 on hypersensitivity. Co‐application of CB2 receptor antagonist SR144528 reversed WIN 55,212‐2's effect on mechanical hypersensitivity on day 2 only.Conclusions and implications:These data support a peripheral antihyperalgesic effect of WIN 55,212‐2 when delivered directly to the site of a nerve injury at systemically inactive doses.British Journal of Pharmacology (2007) 151, 292–302. doi:10.1038/sj.bjp.0707210
Oral administration of Ginkgo biloba extract, EGb‐761 inhibits thermal hyperalgesia in rodent models of inflammatory and post‐surgical pain
Authors: Biddlestone L , Corbett A D , Dolan S 
Published: March 2007

Background and purpose:Studies in vitro suggest that the standardised extract of Ginkgo biloba, EGb‐761 has anti‐inflammatory properties and modulatory effects on key pain‐related molecules. This study investigated the analgesic and anti‐inflammatory effects of EGb‐761 on carrageenan‐induced inflammatory and hindpaw incisional pain.Experimental approach:Adult male Wistar rats (n=6‐10/group; 250‐420 g) were injected intradermally with carrageenan into the left hindpaw or anaesthetised with isoflurane (2%) and a longitudinal 1 cm incision was made through the skin, fascia and plantaris muscle of the hindpaw. EGb‐761 (3, 10, 30, 100 or 300 mg kg−1), diclofenac (5 mg kg−1) or drug‐vehicle was administered 3 h post‐carrageenan/post‐surgery. Hindpaw withdrawal latency (in seconds) to thermal stimulation, response threshold (in grams) to mechanical stimulation and paw volume were measured.Key results:Carrageenan induced significant mechanical allodynia, thermal hyperalgesia and paw oedema at 6 h post‐carrageenan, while paw incision surgery induced significant mechanical allodynia and thermal hyperalgesia at 6 and 24 h post‐surgery. Administration of EGb‐761 dose‐dependently inhibited thermal hyperalgesia and was equally effective as diclofenac (5 mg kg−1) in both the carrageenan and hindpaw incision model. EGb‐761 had no effect on carrageenan‐ or incision‐induced mechanical allodynia or paw oedema. Diclofenac significantly reduced mechanical allodynia in both models and carrageenan‐induced paw oedema.Conclusions and Implications:EGb‐761 dose‐dependently alleviates acute inflammatory and surgically induced thermal hyperalgesia and is comparable to diclofenac, a commonly prescribed non‐steroidal anti‐inflammatory drug. This indicates that EGb‐761 has analgesic potential in acute inflammatory pain.British Journal of Pharmacology (2007) 151, 285–291. doi:10.1038/sj.bjp.0707220
Characterization of the postjunctionalα2C‐adrenoceptor mediating vasoconstriction to UK14304 in porcine pulmonary veins
Authors: Görnemann T , von Wenckstern H , Kleuser B , Villalón C M , Centurión D , Jähnichen S , Pertz H H 
Published: March 2007

Background and purpose:In terms of postjunctional α2‐adrenoceptors in the pulmonary circulation, no evidence is available with regard to the receptor subtypes mediating vasoconstriction. Therefore, we characterized the α2‐adrenoceptor subtypes mediating contraction in isolated porcine pulmonary veins.Experimental approach:α‐adrenoceptor‐mediated vasoconstriction was studied using a tissue bath protocol. mRNA profile and relative quantification of α2‐adrenoceptor subtypes were determined in porcine pulmonary veins using reverse‐transcriptase polymerase chain reaction (RT‐PCR) and real‐time PCR.Key results:In porcine pulmonary veins, noradrenaline, phenylephrine (α1‐adrenoceptor agonist), UK14304 and clonidine (α2‐adrenoceptor agonists) caused concentration‐dependent contractions. The rank order of agonist potency was: NA≈UK14304≈clonidine > phenylephrine. UK14304 responses were antagonised by MK912 (noncompetitive antagonist parameter pD’2: 10.1), rauwolscine (pKB: 9.5), yohimbine (pKB: 9.1), WB4101 (pKB: 8.7), ARC239 (pKB: 7.5), prazosin (pKB: 7.1) and BRL44408 (pKB: 7.0). Antagonist potencies fitted best with radioligand binding data (pKi) at the human recombinant α2C‐adrenoceptor (r2= 0.96,P= 0.0001). Correlation with α2B‐adrenoceptors was lower (r2= 0.74,P> 0.01) and no correlation was obtained with α2A‐adrenoceptors. Moreover, RT‐PCR studies in porcine pulmonary veins showed mRNA signals for α2A‐ and α2C‐adrenoceptors, but not for α2B‐adrenoceptors, whilst real‐time PCR studies indicated a prominent expression of α2C‐adrenoceptor mRNA.Conclusions and Implications:Postjunctional α2C‐adrenoceptors mediated contraction in porcine pulmonary veins. α1‐Adrenoceptors also seem to be present in this tissue. Since α2‐adrenoceptor responsiveness is increased when pulmonary vascular tone is elevated, α2C‐adrenoceptor antagonists may be beneficial in diseases such as pulmonary hypertension or congestive heart failure.British Journal of Pharmacology(2007)151, 186–194. doi:10.1038/sj.bjp.0707221
Melatonin inhibits nitric oxide production by microvascular endothelial cellsin vivoandin vitro
Authors: Silva C L M , Tamura E K , Macedo S M D , Cecon E , Bueno‐Alves L , Farsky S H P , Ferreira Z S , Markus R P 
Published: March 2007

Background and purpose:We have previously shown that melatonin inhibits bradykinin‐induced NO production by endothelial cellsin vitro.The purpose of this investigation was to extend this observation to anin vivocondition and to explore the mechanism of action of melatonin.Experimental approach:RT‐PCR assays were performed with rat cultured endothelial cells. The putative effect of melatonin upon arteriolar tone was investigated by intravital microscopy while NO production by endothelial cellsin vitrowas assayed by fluorimetry, and intracellular Ca2+measurements were assayed by confocal microscopy.Key results:No expression of the mRNA for the melatonin synthesizing enzymes, arylalkylamine N‐acetyltransferase and hydroxyindole‐O‐methyltransferase, or for the melatonin MT2receptor was detected in microvascular endothelial cells. Melatonin fully inhibitedL‐NAME‐sensitive bradykinin‐induced vasodilation and also inhibited NO production induced by histamine, carbachol and 2‐methylthio ATP, but did not inhibit NO production induced by ATP orα,β‐methylene ATP. None of its inhibitory effects was prevented by the melatonin receptor antagonist, luzindole. In nominally Ca2+‐free solution, melatonin reduced intracellular Ca2+mobilization induced by bradykinin (40%) and 2‐methylthio ATP (62%) but not Ca2+mobilization induced by ATP.Conclusions and implications:We have confirmed that melatonin inhibited NO production bothin vivoandin vitro. In addition, the melatonin effect was selective for some G protein‐coupled receptors and most probably reflects an inhibition of Ca2+mobilization from intracellular stores.British Journal of Pharmacology(2007)151, 195–205. doi:10.1038/sj.bjp.0707225
Increased insulin sensitivity and reduced micro and macro vascular disease induced by 2‐deoxy‐D‐glucose during metabolic syndrome in obese JCR: LA‐cp rats
Authors: Russell J C , Proctor S D 
Published: March 2007

Background and purpose:The metabolic syndrome, characterized by obesity, insulin resistance and dyslipidemia, is a major cause of cardiovascular disease. The origins of the syndrome have been hypothesized to lie in continuous availability of energy dense foods in modern societies. In contrast, human physiology has evolved in an environment of sporadic food supply and frequent food deprivation. Intermittent food restriction in rats has previously been shown to lead to reduction of cardiovascular risk and a greater life span. The non‐metabolizable glucose analogue, 2‐deoxy‐D‐glucose (2‐DG) is taken up by cells and induces pharmacological inhibition of metabolism of glucose. We hypothesized that intermittent inhibition of glucose metabolism, a metabolic deprivation, may mimic intermittent food deprivation and ameliorate metabolic and pathophysiological aspects of the metabolic syndrome.Experimental approach:Insulin resistant, atherosclerosis‐prone JCR:LA‐cp rats were treated with 2‐DG (0.3% w/w in chow) on an intermittent schedule (2 days treated, one day non‐treated, two days treated and two days non‐treated) or continuously at a dose to give an equivalent averaged intake.Key results:Intermittent 2‐DG‐treatment improved insulin sensitivity, which correlated with increased adiponectin concentrations. Further, intermittent treatment (but not continuous treatment) reduced plasma levels of leptin and the inflammatory cytokine IL‐1β. Both 2‐DG treatments reduced micro‐vascular glomerular sclerosis, but only the intermittent schedule improved macro‐vascular dysfunction.Conclusions and implications:Our findings are consistent with reduction in severity of the metabolic syndrome and protection against end stage micro‐ and macro‐vascular disease through intermittent metabolic deprivation at a cellular level by inhibition of glucose oxidation with 2‐DG.British Journal of Pharmacology (2007) 151, 216–225. doi:10.1038/sj.bjp.0707226
The bisphosphonate alendronate improves the damage associated with trinitrobenzenesulfonic acid‐induced colitis in rats
Authors: Ballester I , Daddaoua A , López‐Posadas R , Nieto A , Suárez M D , Zarzuelo A , Martínez‐Augustin O , de Medina F Sánchez 
Published: March 2007

Background and purpose:The nitrogen‐containing bisphosphonates are drugs used successfully in the treatment of osteoporosis. They act inhibiting farnesyl diphosphate synthase. This mechanism may also produce anti‐inflammatory effects. The therapeutic activity of alendronate was tested in vivo using a model of inflammatory bowel disease.Experimental approach:The trinitrobenzenesulfonic acid model of colitis in the rat was used. Rats were treated orally with alendronate and its efficacy compared with that of oral sulphasalazine or vehicle, starting 2 h after colitis induction. The status of the animals was assessed 5 days later.Key results:Alendronate treatment (25 or 75 mg kg‐1 day‐1) resulted in a decrease in the colonic damage score and loss of body weight (at 25 mg kg‐1 day‐1 only). This was associated to a dramatic reduction in the mRNA levels of interleukin 1β (IL‐1β), monocyte chemoattractant protein 1 (MCP‐1) and interleukin 1 receptor antagonist (IL‐1ra). The magnitude of the beneficial effect was comparable to that of sulphasalazine (at a 6‐20 fold higher dose). Thus sulphasalazine post‐treatment reduced the mRNA levels of IL‐1β/IL‐1ra and MCP‐1 to the same extent as alendronate and additionally lowered colonic alkaline phosphatase activity, but failed to affect body weight loss or colonic damage score. Alendronate failed to exert beneficial effects when administered intraperitoneally.Conclusions and Implications:Oral but not intraperitoneal alendronate significantly protected the colon in experimental rat colitis. Inflammatory bowel disease patients might benefit from exposure to oral alendronate.British Journal of Pharmacology (2007) 151, 206–215. doi:10.1038/sj.bjp.0707227
Stem cells from umbilical cord blood differentiate into myotubes and express dystrophin in vitro only after exposure to in vivo muscle environment
Authors: Nunes Viviane A. , Cavaçana Natale , Canovas Martha , Strauss Bryan E. , Zatz Mayana 
Published: March 2007

Background information. Duchenne muscular dystrophy is a disease characterized by progressive and irreversible muscle degeneration for which there is no therapy. HUCB (human umbilical cord blood) has been considered as an important source of haematopoietic and mesenchymal stem cells, each having been shown to differentiate into distinct cell types. However, it remains unclear if these cells are able to differentiate into muscle cells.Results. We have showed that stem cells from HUCB did not differentiate into myotubes or express dystrophin when cultured in muscle‐conditioned medium or with human muscle cells. However, delivery of GFP (green fluorescent protein)‐transduced mononucleated cells from HUCB, which comprises both haematopoietic and mesenchymal populations, into quadriceps muscle of mdx (mouse dystrophy X‐chromosome linked) mice resulted in the expression of human myogenic markers. After recovery of these cells from mdx muscle and in vitro cultivation, they were able to fuse and form GFP‐positive myotubes that expressed dystrophin.Conclusions. These results indicate that chemical factors and cell‐to‐cell contact provided by in vitro conditions were not enough to trigger the differentiation of stem cells into muscle cells. Nevertheless, we showed that the HUCB‐derived stem cells were capable of acquiring a muscle phenotype after exposure to an in vivo muscle environment, which was required to activate the differentiation programme.
A new in vitro wound model based on the co‐culture of human dermal microvascular endothelial cells and human dermal fibroblasts
Authors: Oberringer Martin , Meins Claudia , Bubel Monika , Pohlemann Tim 
Published: March 2007

Background information. Different in vitro models, based on co‐culturing techniques, can be used to investigate the behaviour of cell types, which are relevant for human wound and soft‐tissue healing. Currently, no model exists to describe the behaviour of fibroblasts and microvascular endothelial cells under wound‐specific conditions. In order to develop a suitable in vitro model, we characterized co‐cultures comprising NHDFs (normal human dermal fibroblasts) and HDMECs (human dermal microvascular endothelial cells). The CCSWMA (co‐culture scratch wound migration assay) developed was supported by direct visualization techniques in order to investigate a broad spectrum of cellular parameters, such as migration and proliferation activity, the differentiation of NHDFs into MFs (myofibroblasts) and the expression of endothelin‐1 and ED‐A‐fibronectin (extra domain A fibronectin). The cellular response to hypoxia treatment, as one of the crucial conditions in wound healing, was monitored.Results. The comparison of the HDMEC—NHDF co‐culture with the respective mono‐cultures revealed that HDMECs showed a lower proliferation activity when co‐cultured, but their number was stable throughout a period of 48 h. NHDFs in co‐culture were slightly slower at proliferating than in the mono‐culture. The MF population was stable for 48 h in the co‐culture, as well as in NHDF mono‐culture. Co‐cultures and HDMEC mono‐cultures were characterized by a slower migration rate than NHDF mono‐cultures. Hypoxia decreased both cell proliferation and migration in the mono‐cultures, as well as in the co‐cultures, indicating the general suitability of the assay. Exclusively, in co‐cultures well‐defined cell clusters comprising HDMECs and MFs formed at the edges of the in vitro wounds.Conclusions. On the basis of these results, the CCSWMA developed using co‐cultures, including HDMECs, NHDFs and MFs, proved to be an effective tool to directly visualize cellular interaction. Therefore, it will serve in the future to evaluate the influence of wound‐healing‐related factors in vitro, as shown for hypoxia in the present study.
First step of the cell‐penetrating peptide mechanism involves Rac1 GTPase‐dependent actin‐network remodelling
Authors: Gerbal‐Chaloin Sabine , Gondeau Claire , Aldrian‐Herrada Gudrun , Heitz Frédéric , Gauthier‐Rouvière Cécile , Divita Gilles 
Published: March 2007

Background information. Application of CPPs (cell‐penetrating peptides) constitutes a promising strategy for the intracellular delivery of therapeutic molecules. The non‐covalent approach based on the amphipathic peptide MPG has been successfully used to improve the delivery of biologically active macromolecules, both in cellulo and in vivo, through a mechanism independent of the endosomal pathway and mediated by the membrane potential.Results. In the present study, we have investigated the first step of the cellular uptake mechanism of MPG and shown that both MPG and MPG—cargo complexes interact with the extracellular matrix through the negatively charged heparan sulfate proteoglycans. We demonstrated that initiation of cellular uptake constitutes a highly dynamic mechanism where the binding of MPG or the MPG—cargo to the extracellular matrix is rapidly followed by a remodelling of the actin network associated with the activation of the GTPase Rac1. We suggest that MPG‐induced clustering of the glycosaminoglycan platform constitutes the ‘onset’ of the cellular uptake mechanism, thereby increasing membrane dynamics and membrane fusion processes. This process favours cell entry of MPG or MPG—DNA complexes, which is further controlled by the ability of MPG to induce a local membrane destabilization.Conclusions. Although CPPs are taken up through different pathways and mechanisms, the initial step involves electrostatic interactions with the glycosaminoglycan platform, and the dynamics of associated membrane microdomains can be generalized to most non‐viral delivery systems.
Arabidopsis Nucleolin Affects Plant Development and Patterning
Authors: Petricka Jalean Joyanne , Nelson Timothy Mark 
Published: March 2007

AbstractNucleolin is a major nucleolar protein implicated in many aspects of ribosomal biogenesis, including early events such as processing of the large 35S preribosomal RNA. We found that the Arabidopsis (Arabidopsis thaliana) parallel1 (parl1) mutant, originally identified by its aberrant leaf venation, corresponds to the Arabidopsis nucleolin gene. parl1 mutants display parallel leaf venation, aberrant localization of the provascular marker Athb8:β-glucuronidase, the auxin-sensitive reporter DR5:β-glucuronidase, and auxin-dependent growth defects. PARL1 is highly similar to the yeast (Saccharomyces cerevisiae) nucleolin NUCLEAR SIGNAL RECOGNITION 1 (NSR1) multifunctional protein; the Arabidopsis PARL1 gene can rescue growth defects of yeast nsr1 null mutants. This suggests that PARL1 protein may have roles similar to those of the yeast nucleolin in nuclear signal recognition, ribosomal processing, and ribosomal subunit accumulation. Based on the range of auxin-related defects in parl1 mutants, we propose that auxin-dependent organ growth and patterning is highly sensitive to the efficiency of nucleolin-dependent ribosomal processing.
Comparative Genetic Mapping inBoechera stricta, a Close Relative of Arabidopsis
Authors: Schranz M. Eric , Windsor Aaron J. , Song Bao-hua , Lawton-Rauh Amy , Mitchell-Olds Thomas 
Published: March 2007

AbstractThe angiosperm family Brassicaceae contains both the research model Arabidopsis (Arabidopsis thaliana) and the agricultural genus Brassica. Comparative genomics in the Brassicaceae has largely focused on direct comparisons between Arabidopsis and the species of interest. However, the reduced genome size and chromosome number (n = 5) of Arabidopsis complicates comparisons. Arabidopsis shows extensive genome and chromosome reshuffling compared to its close relatives Arabidopsis lyrata and Capsella rubella, both with n = 8. To facilitate comparative genomics across the Brassicaceae we recently outlined a system of 24 conserved chromosomal blocks based on their positions in an ancestral karyotype of n = 8, rather than by their position in Arabidopsis. In this report we use this system as a tool to understand genome structure and evolution in Boechera stricta (n = 7). B. stricta is a diploid, sexual, and highly self-fertilizing species occurring in mostly montane regions of western North America. We have created an F2 genetic map of B. stricta based on 192 individuals scored at 196 microsatellite and candidate gene loci. Single-nucleotide polymorphism genotyping of 94 of the loci was done simultaneously using an Illumina bead array. The total map length is 725.8 cM, with an average marker spacing of 3.9 cM. There are no gaps greater than 19.3 cM. The chromosomal reduction from n = 8 to n = 7 and other genomic changes in B. stricta likely involved a pericentric inversion, a chromosomal fusion, and two reciprocal translocations that are easily visualized using the genomic blocks. Our genetic map will facilitate the analysis of ecologically relevant quantitative variation in Boechera.
The Mitogen-Activated Protein Kinase Cascade MKK3–MPK6 Is an Important Part of the Jasmonate Signal Transduction Pathway in Arabidopsis
Authors: Takahashi Fuminori , Yoshida Riichiro , Ichimura Kazuya , Mizoguchi Tsuyoshi , Seo Shigemi , Yonezawa Masahiro , Maruyama Kyonoshin , Yamaguchi-Shinozaki Kazuko , Shinozaki Kazuo 
Published: March 2007

Abstract
The plant hormone jasmonic acid (JA) plays a key role in the environmental stress responses and developmental processes of plants. Although ATMYC2/JASMONATE-INSENSITIVE1 (JIN1) is a major positive regulator of JA-inducible gene expression and essential for JA-dependent developmental processes in Arabidopsis thaliana, molecular mechanisms underlying the control of ATMYC2/JIN1 expression remain largely unknown. Here, we identify a mitogen-activated protein kinase (MAPK) cascade, MAPK KINASE 3 (MKK3)–MAPK 6 (MPK6), which is activated by JA in Arabidopsis. We also show that JA negatively controls ATMYC2/JIN1 expression, based on quantitative RT-PCR and genetic analyses using gain-of-function and loss-of-function mutants of the MKK3–MPK6 cascade. These results indicate that this kinase unit plays a key role in JA-dependent negative regulation of ATMYC2/JIN1 expression. Both positive and negative regulation by JA may be used to fine-tune ATMYC2/JIN1 expression to control JA signaling. Moreover, JA-regulated root growth inhibition is affected by mutations in the MKK3–MPK6 cascade, which indicates important roles in JA signaling. We provide a model explaining how MPK6 can convert three distinct signals—JA, pathogen, and cold/salt stress—into three different sets of responses in Arabidopsis.