bluuebunny/crossref_metadata_2025_split huggingface dataset:
The GABAB receptor agonist CGP44532 and the positive modulator GS39783 reverse some behavioural changes related to positive syndromes of psychosis in mice
Authors: Wierońska JM , Kusek M , Tokarski K , Wabno J , Froestl W , Pilc A 
Published: March 2011

BACKGROUND AND PURPOSE An important role of GABAergic neurotransmission in schizophrenia was proposed a long time ago, but there is limited data to support this hypothesis. In the present study we decided to investigate GABAB receptor ligands in animal models predictive for the antipsychotic activity of drugs. The GABAB receptor antagonists CGP51176 and CGP36742, agonist CGP44532 and positive allosteric modulator GS39783 were studied.EXPERIMENTAL APPROACH The effects of all ligands were investigated in MK‐801‐ and amphetamine‐induced hyperactivity tests. The anti‐hallucinogenic‐like effect of the compounds was screened in the model of head twitches induced by (±)1‐(2.5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI). Furthermore, the effect of GS39783 and CGP44532 on DOI‐induced frequency of spontaneous excitatory postsynaptic currents (EPSCs) in slices from mouse brain frontal cortices was investigated. The anti‐cataleptic properties of the compounds were also assessed.KEY RESULTS The GABAB receptor activators CGP44532 and GS39783 exhibited antipsychotic‐like effects both in the MK‐801‐ and amphetamine‐induced hyperactivity tests, as well as in the head‐twitch model in mice. Such effects were not observed for the GABAB receptor antagonists. DOI‐induced increased frequency of spontaneous EPSCs was also decreased by the compounds. Moreover, CGP44532 and GS39783 inhibited haloperidol‐induced catalepsy and EPSCs.CONCLUSION AND IMPLICATIONS These data suggest that selective GABAB receptor activators may be useful in the treatment of psychosis.
Effects of lidocaine with epinephrine or with buffer on wound healing in rat skin
Authors: Rodrigues Felipe V. , Hochman Bernardo , Wood Viviane T. , Simões Manuel J. , Juliano Yara , Ferreira Lydia M. 
Published: March 2011

ABSTRACTLidocaine blocks nociceptive fibers, preventing initial wound signaling and mast cell degranulation. It is hypothesized that epinephrine and buffer affect the wound healing by potentiating lidocaine blockage. This double‐blind, randomized, self‐controlled study investigated this possibility using male Wistar rats, which were injected with 2 mL of different solutions into the left and right sides of the back. Then, each side was incised and sutured. Sixty rats were divided in three groups: saline solution (SS) and lidocaine; lidocaine and lidocaine with buffer; lidocaine with epinephrine and lidocaine with epinephrine and buffer. Half of each group was sacrificed 7 days after surgery and the remaining after 21 days. A sample of each wound was obtained and quantified for the level of collagen present using computer morphometry and for mast cell quantity. There were no differences between animals with regard to the collagen. However, mast cell levels in the same animal significantly differed between SS × lidocaine. Comparison of the same injected substance between animals with different healing dates showed a significant effect on collagen SS and on all mast cells, except SS. Lidocaine affected collagenization and decreased the initial quantity of mast cells at the wound site.
Lysophosphatidic acid stimulates epidermal growth factor‐family ectodomain shedding and paracrine signaling from human lung fibroblasts
Authors: Shiomi Tetsuya , Boudreault Francis , Padem Nurcicek , Higashiyama Shigeki , Drazen Jeffrey M. , Tschumperlin Daniel J. 
Published: March 2011

ABSTRACTLysophospatidic acid (LPA) is a bioactive lipid mediator implicated in tissue repair and wound healing. It mediates diverse functional effects in fibroblasts, including proliferation, migration and contraction, but less is known about its ability to evoke paracrine signaling to other cell types involved in wound healing. We hypothesized that human pulmonary fibroblasts stimulated by LPA would exhibit ectodomain shedding of epidermal growth factor receptor (EGFR) ligands that signal to lung epithelial cells. To test this hypothesis, we used alkaline phosphatase‐tagged EGFR ligand plasmids transfected into lung fibroblasts, and enzyme‐linked immunosorbent assays to detect shedding of native ligands. LPA induced shedding of alkaline phosphatase‐tagged heparin‐binding epidermal growth factor (HB‐EGF), amphiregulin, and transforming growth factor‐a; non‐transfected fibroblasts shed amphiregulin and HBEGF under baseline conditions, and increased shedding of HB‐EGF in response to LPA. Treatment of fibroblasts with LPA resulted in elevated phosphorylation of extracellular signal‐regulated kinase 1/2, enhanced expression of mRNA for c‐fos, HB‐EGF and amphiregulin, and enhanced proliferation at 96 hours. However, none of these fibroblast responses to LPA required ectodomain shedding or EGFR activity. To test the ability of LPA to stimulate paracrine signaling from fibroblasts, we transferred conditioned medium from LPA‐stimulated cells, and found enhanced EGFR and extracellular signal‐regulated kinase 1/2 phosphorylation in reporter A549 cells in excess of what could be accounted for by transferred LPA alone. These data show that LPA mediates EGF‐family ectodomain shedding, resulting in enhanced paracrine signaling from lung fibroblasts to epithelial cells.
Comparison of negative pressure wound therapy with an ultraportable mechanically powered device vs. traditional electrically powered device for the treatment of chronic lower extremity ulcers: A multicenter randomized‐controlled trial
Authors: Armstrong David G. , Marston William A. , Reyzelman Alexander M. , Kirsner Robert S. 
Published: March 2011

ABSTRACTThe purpose of this study was to compare the ultraportable mechanically powered Smart Negative Pressure (SNaP®) Wound Care System to the traditional electrically powered Vacuum‐Assisted Closure (VAC®) Therapy System in the treatment of chronic lower extremity wounds. This 12‐center randomized‐controlled trial of patients with noninfected, nonischemic, nonplantar lower extremity wounds had enrolled 65 patients, as of January 5, 2010, at the time of a planned interim analysis. Subjects were randomly assigned to treatment with either the SNaP® or VAC® Systems. The trial evaluated treatment for up to 16 weeks or till complete closure was achieved. Fifty‐three patients (N=27 SNaP®, N=26 VAC®) completed at least 4 weeks of therapy. Thirty‐three patients (N=18 SNaP®, N=15 VAC®) completed the study with either healing or 16 weeks of therapy. At the time of planned interim analysis, no significant differences (p=0.99) in the proportion of subjects healed between the two devices evaluated were found. In addition, the percent wound size reduction between treatment groups was not significantly different at 4, 8, 12, and 16 weeks, with noninferiority analysis at 4 weeks of treatment reaching the p‐value <0.05 significance level (*p=0.019). These interim data suggest no difference in wound closure between the SNaP® System and the VAC® System in the population studied. We look forward to the final analysis results.
Fish oil supplementation alters levels of lipid mediators of inflammation in microenvironment of acute human wounds
Authors: McDaniel Jodi C. , Massey Karen , Nicolaou Anna 
Published: March 2011

ABSTRACTChronic wounds often result from prolonged inflammation involving excessive polymorphonuclear leukocyte activity. Studies show that the ω‐3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oils generate bioactive lipid mediators that reduce inflammation and polymorphonuclear leukocyte recruitment in numerous inflammatory disease models. This study's purpose was to test the hypotheses that boosting plasma levels of EPA and DHA with oral supplementation would alter lipid mediator levels in acute wound microenvironments and reduce polymorphonuclear leukocyte levels. Eighteen individuals were randomized to 28 days of either EPA+DHA supplementation (Active Group) or placebo. After 28 days, the Active Group had significantly higher plasma levels of EPA (p<0.001) and DHA (p<0.001) than the Placebo Group and significantly lower wound fluid levels of two 15‐lipoxygenase products of ω‐6 polyunsaturated fatty acids (9‐hydroxyoctadecadienoic acid [p=0.033] and 15‐hydroxyeicosatrienoic acid [p=0.006]), at 24 hours postwounding. The Active Group also had lower mean levels of myeloperoxidase, a leukocyte marker, at 12 hours and significantly more reepithelialization on Day 5 postwounding. We suggest that lipid mediator profiles can be manipulated by altering polyunsaturated fatty acid intake to create a wound microenvironment more conducive to healing.
Preconditioning with cobalt protoporphyrin protects human gastric mucosal cells from deoxycholate‐induced apoptosis
Authors: Lawson Tina E. , Redlak Maria J. , Yager Dorne R. 
Published: March 2011

ABSTRACTIn this study, a known inducer of heme oxygenase‐1 (HO‐1) expression, cobalt protoporphyrin, and the introduction of a recombinant plasmid expressing HO‐1 were examined for their ability to protect gastric epithelial cells from deoxycholate‐induced injury. Physiologic levels of the secondary bile salt induce apoptosis in a human gastric adenocarcinoma mucosal cell line. Cobalt protoporphyrin induced expression of HO‐1 protein with maximal levels attaining a plateau at 48 hours. Pretreatment with cobalt protoporphyrin before challenge with 200 μM deoxycholate inhibited cell death, DNA fragmentation, the appearance of cytosolic nucleosomes, and cleavage of caspase‐3, caspase‐9, and poly‐(ADP‐ribose) polymerase 1. Similarly, expression of HO‐1 by introduction of a recombinant plasmid also showed a resistance to deoxycholate‐induced apoptosis. These results implicate a possible role for HO‐1 in modulating apoptosis in gastric epithelial cells.
Cellular/extracellular matrix cross‐talk in scar evolution and control
Authors: Widgerow Alan D. 
Published: March 2011

ABSTRACTThe principles of scar evolution and control are recognized and defined. Further clarity has been shed on these principles with the elucidation and elaboration of the sequence of events occurring at a molecular level. Cellular cross‐talk among structures in the cell cytosol, in the cellular nucleus, and outside the cell within in the extracellular matrix is continuous and controlling in nature. This interaction or “dynamic reciprocity” takes place via a series of signals, ionic messenger shifts, protein activation, and receptor transactions. The described principles are now able to be defined in terms of cellular/extracellular matrix interactions and the identification of the cross‐talk involved in scar evolution and maturation presents the possibility of influencing the “wording” of this cross‐talk to improve scar outcome. The principles of mechanostimulation and scar support, hydration occlusion, controlled inflammation, and collagen/extracellular remodeling are discussed with possible interventions in each category.
Neural network adapted to wound cell analysis in surgical patients
Authors: Viljanto Jouko , Koski Antti 
Published: March 2011

ABSTRACTAssessment of the real state of wound healing of closed surgical wounds is uncertain both clinically and from conventional laboratory tests. Therefore, a novel approach based on early analysis of exactly timed wound cells, computerized further with an artificial neural network, was developed. At the end of routine surgery performed on 481 children under 18 years of age, a specific wound drain Cellstick™ was inserted subcutaneously between the wound edges to harvest wound cells. The Cellsticks™ were removed from 1 to 50 hours, mainly at hour 3 or 24 postsurgery. Immediately, the cellular contents were washed out using a pump constructed for the purpose. After cytocentrifugation, the cells were stained and counted differentially. Based on their relative proportions at selected time intervals, an artificial self‐organizing neural map was developed. This was further transformed to a unidirectional linear graph where each node represents one set of relative cell quantities. As early as 3 hours, but more precisely 24 hours after surgery, the location of the nodes on this graph showed individually the patients' initial speed of wound inflammatory cell response. Similarly, timed Cellstick™ specimens from new surgical patients could be analyzed, computerized, and compared with these node values to assess their initial speed in wound inflammatory cell response. Location of the node on the graph does not express the time lapse after surgery but the speed of wound inflammatory cell response in relation to that of other patients.
Incidence of methemoglobinemia in patients receiving cerium nitrate and silver sulfadiazine for the treatment of burn wounds: A burn center's experience
Authors: Kath Melissa A. , Shupp Jeffrey W. , Matt Sarah E. , Shaw Jesse D. , Johnson Laura S. , Pavlovich Anna R. , Brant Jennifer D. , Mete Mihriye , Jeng James C. , Jordan Marion H. 
Published: March 2011

ABSTRACTIn 1976, the combination of cerium nitrate and silver sulfadiazine was introduced as a topical therapy for burn wounds. Experience with a locally prepared combination agent has shown physical change of the eschar and delayed subeschar bacterial colonization. A potential systemic complication of this treatment is the development of methemoglobinemia (Met‐Hba) due to the oxidizing nature of Ce(NO3)3. Met‐Hba has a spectrum of clinical consequences, ranging from headache and cyanosis to cardiac ischemia, hypotension, and even death. Given the frequent use of this combination agent at our burn center, a retrospective review was conducted to evaluate the incidence of Met‐Hba. A query of pharmacy records revealed 170 patients from January 2005 to October 2009 that had received this treatment. Eighteen patients (∼10%) developed Met‐Hba as noted on arterial blood gas (methemoglobin>3%) and only three patients (∼2%) had methemoglobin levels >10%. In the majority of cases, there were no clinical symptoms of Met‐Hba. Most patients' relative hypoxia resolved with cessation of treatment; however, five patients required treatment with methylene blue. The presence of Met‐Hba associated with this topical therapy can be diagnosed early by vigilant monitoring, thereby reducing morbidity and mortality. In our experience, cerium combined with silver sulfadiazine is a valuable and safe treatment for deep partial and full‐thickness burn wounds.
Epidemiology of chronic cutaneous wounds in China
Authors: Jiang Yufeng , Huang Sha , Fu Xiaobing , Liu Hongwei , Ran Xingwu , Lu Shuliang , Hu Dahai , Li Qiang , Zhang Hongwei , Li Ying , Wang Runxiu , Xie Ting , Cheng Biao , Wang Lingfeng , Liu Yi , Ye Xiangbai , Han Chunmao , Chen Huade 
Published: March 2011

ABSTRACTChronic cutaneous wounds represent a major health care burden in China. However, limited information exists regarding the epidemiologic changes associated with recent social and economic development. We designed a cross‐sectional survey in 2,513 patients who underwent treatment of chronic cutaneous wounds from a nationally representative sample in 17 hospitals between 2007 and 2008. Results revealed the prevalence of chronic cutaneous wounds among hospitalized patients was 1.7‰. Patient ages ranged from 18 days to 96 years (median, 58 years). The highest ratios were among 40–60 and 60–80‐year‐old patients (31% and 38%, respectively). The leading causes of chronic cutaneous wounds were diabetes (31.3% men, 35.3% women) trauma (26.4% men, 19.2% women). Manual workers (38.5% men, 29.3% women) and retirees (27.9% men, 23.5% women) accounted for over half the chronic cutaneous wound patients. Regarding treatments, only 22.4% were treated with modern dressings or other novel technologies and more patients received antibiotics (77.8%). Treatment was paid for by the patients in 42.3% of cases, by social medical insurance in 25.0%, by commercial medical insurance in 4.8%, while 27.9% received free medical care. Approximately half the patients' wounds were completely healed at discharge (1,345/2,513). In conclusion, diabetes has recently become the leading cause of chronic cutaneous wounds in China. The large population and considerable financial burden mean that serious attention should be paid to the early detection, prevention and diagnosis of chronic cutaneous wounds, and suggest that an overall health insurance system should be established, especially for the elderly.
Formulated collagen gel accelerates healing rate immediately after application in patients with diabetic neuropathic foot ulcers
Authors: Blume Peter , Driver Vickie R. , Tallis Arthur J. , Kirsner Robert S. , Kroeker Roy , Payne Wyatt G. , Wali Soma , Marston William , Dove Cyaandi , Engler Robert L. , Chandler Lois A. , Sosnowski Barbara K. 
Published: March 2011

ABSTRACTWe assessed the safety and efficacy of Formulated Collagen Gel (FCG) alone and with Ad5PDGF‐B (GAM501) compared with Standard of Care (SOC) in patients with 1.5–10.0 cm2 chronic diabetic neuropathic foot ulcers that healed <30% during Run‐in. Wound size was assessed by planimetry of acetate tracings and photographs in 124 patients. Comparison of data sets revealed that acetate tracings frequently overestimated areas at some sites. For per‐protocol analysis, 113 patients qualified using acetate tracings but only 82 qualified using photographs. Prior animal studies suggested that collagen alone would have little effect on healing and would serve as a negative control. Surprisingly trends for increased incidence of complete closure were observed for both GAM501 (41%) and FCG (45%) vs. Standard of Care (31%). By photographic data, Standard of Care had no significant effect on change in wound radius (mm/week) from during Run‐in to Week 1 (−0.06±0.32 to 0.78±1.53, p=ns) but both FCG (−0.08±0.61 to 1.97±1.77, p<0.002) and GAM501 (−0.02±0.58 to 1.46±1.37, p<0.002) significantly increased healing rates that gradually declined over subsequent weeks. Both GAM501 and FCG appeared to be safe and well tolerated, and alternate dosing schedules hold promise to improve overall complete wound closure in adequately powered trials.
The recruitment of bone marrow‐derived cells to skin wounds is independent of wound size
Authors: Verstappen Jochem , Katsaros Christos , Kuijpers‐Jagtman Anne Marie , Torensma Ruurd , Von den Hoff Johannes W. 
Published: March 2011

ABSTRACTWounded skin recruits progenitor cells, which repair the tissue defect. These cells are derived from stem cells in several niches in the skin. In addition, bone marrow‐derived cells (BMDCs) are recruited and contribute to wound repair. We hypothesized that larger wounds recruit more cells from the bone marrow. Wild‐type rats were lethally irradiated and transplanted with bone marrow cells from green fluorescent protein (GFP)‐transgenic rats. Seven weeks later, 4, 10, and 20 mm wounds were created. The wound tissue was harvested after 14 days. The density of GFP‐positive cells in the wounds and the adjacent tissues was determined, as well as in normal skin from the flank. Bone marrow‐derived myofibroblasts, activated fibroblasts, and macrophages were also quantified. After correction for cell density, the recruitment of BMDCs (23±11%) was found to be independent of wound size. Similar fractions of GFP‐positive cells were also detected in nonwounded adjacent tissue (29±11%), and in normal skin (26±19%). The data indicate that BMDCs are not preferentially recruited to skin wounds. Furthermore, wound size does not seem to affect the recruitment of BMDCs.
Adults with a history of possible Dravet syndrome: An illustration of the importance of analysis of the SCN1A gene
Authors: Verbeek Nienke E. , van Kempen Marjan , Gunning W. Boudewijn , Renier Willy O. , Westland Birgit , Lindhout Dick , Brilstra Eva H. 
Published: March 2011

SummaryMost patients with Dravet syndrome have de novo mutations in the neuronal voltage‐gated sodium channel type 1 (SCN1A) gene. We report on two unrelated fathers with severe childhood epilepsy compatible with a possible diagnosis of Dravet syndrome, who both have a child with Dravet syndrome. Analysis of the SCN1A gene revealed a pathogenic mutation in both children. One father exhibited somatic mosaicism for the mutation detected in his son. A relatively favorable cognitive outcome in patients with Dravet syndrome patients may be explained by somatic mosaicism for the SCN1A mutation in brain tissue. A mild form of Dravet syndrome in adult patients is associated with a high recurrence risk and possibly a more severe epilepsy phenotype in their offspring.
Development of later life spontaneous seizures in a rodent model of hypoxia‐induced neonatal seizures
Authors: Rakhade Sanjay N. , Klein Peter M. , Huynh Thanthao , Hilario‐Gomez Cristina , Kosaras Bela , Rotenberg Alexander , Jensen Frances E. 
Published: March 2011

SummaryPurpose:  To study the development of epilepsy following hypoxia‐induced neonatal seizures in Long‐Evans rats and to establish the presence of spontaneous seizures in this model of early life seizures.Methods:  Long‐Evans rat pups were subjected to hypoxia‐induced neonatal seizures at postnatal day 10 (P10). Epidural cortical electroencephalography (EEG) and hippocampal depth electrodes were used to detect the presence of seizures in later adulthood (>P60). In addition, subdermal wire electrode recordings were used to monitor age at onset and progression of seizures in the juvenile period, at intervals between P10 and P60. Timm staining was performed to evaluate mossy fiber sprouting in the hippocampi of P100 adult rats that had experienced neonatal seizures.Key Findings:  In recordings made from adult rats (P60–180), the prevalence of epilepsy in cortical and hippocampal EEG recordings was 94.4% following early life hypoxic seizures. These spontaneous seizures were identified by characteristic spike and wave activity on EEG accompanied by behavioral arrest and facial automatisms (electroclinical seizures). Phenobarbital injection transiently abolished spontaneous seizures. EEG in the juvenile period (P10–60) showed that spontaneous seizures first occurred approximately 2 weeks after the initial episode of hypoxic seizures. Following this period, spontaneous seizure frequency and duration increased progressively with time. Furthermore, significantly increased sprouting of mossy fibers was observed in the CA3 pyramidal cell layer of the hippocampus in adult animals following hypoxia‐induced neonatal seizures. Notably, Fluoro‐Jade B staining confirmed that hypoxic seizures at P10 did not induce acute neuronal death.Significance:  The rodent model of hypoxia‐induced neonatal seizures leads to the development of epilepsy in later life, accompanied by increased mossy fiber sprouting. In addition, this model appears to exhibit a seizure‐free latent period, following which there is a progressive increase in the frequency of electroclinical seizures.