bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of prostaglandin E2 in the synthesis of the pro‐inflammatory cytokine interleukin‐6 in primary sensory neurons: an in vivo and in vitro study
Authors: St‐Jacques Bruno , Ma Weiya
Published: March 2011

J. Neurochem. (2011) 118, 841–854.

Following various types of nerve injury, cyclooxygenase 2 and prostaglandin E2 (PGE2) are universally and chronically up‐regulated in injured nerves and contribute to the genesis of neuropathic pain. Persistent high levels of PGE2 likely exert chronic effects on nociceptive dorsal root ganglion (DRG) neurons. In the present study, we tested the hypothesis that injured nerve‐derived PGE2 contributes to the up‐regulation of the pro‐inflammatory cytokine interleukin‐6 (IL‐6) in DRG neurons following partial sciatic nerve ligation. In naive adult rats, IL‐6 was expressed in only a few small size DRG neurons which all co‐expressed EP4 receptors. Partial sciatic nerve ligation increased and shifted IL‐6 expression from small to medium and large size damaged DRG neurons. Perineural injection of a selective cyclooxygenase 2 inhibitor or a selective EP4 receptor antagonist significantly suppressed the up‐regulation of IL‐6 in DRG, suggesting that injured nerve derived PGE2 contributes to the de novo synthesis of IL‐6 in DRG neurons through EP4 receptors. In cultured sensory ganglion explants, a stabilized PGE2 analog increased IL‐6 mRNA and protein levels through the activation of EP4, protein kinase A, protein kinase C, extracelluar regulated protein kinase/MAPK, cAMP response element binding protein and NFκB signalling pathways. Taken together, these data indicate that facilitating the de novo synthesis of pain‐related cytokines in injured medium and large size DRG neurons is a novel mechanism underlying the role of injured nerve derived PGE2 in the genesis of neuropathic pain.
Central activation of the cholinergic anti‐inflammatory pathway reduces surgical inflammation in experimental post‐operative ileus
Authors: The FO , Cailotto C , van der Vliet J , de Jonge WJ , Bennink RJ , Buijs RM , Boeckxstaens GE
Published: March 2011

BACKGROUND AND PURPOSE Electrical stimulation of the vagus nerve reduces intestinal inflammation following mechanical handling, thereby shortening post‐operative ileus in mice. Previous studies in a sepsis model showed that this cholinergic anti‐inflammatory pathway can be activated pharmacologically by central administration of semapimod, an inhibitor of p38 mitogen‐activated protein kinase. We therefore evaluated the effect of intracerebroventricular (i.c.v.) semapimod on intestinal inflammation and post‐operative ileus in mice.

EXPERIMENTAL APPROACH Mice underwent a laparotomy or intestinal manipulation 1 h after i.c.v. pre‐treatment with semapimod (1 µg·kg−1) or saline. Drugs were administered through a cannula placed in the left lateral ventricle 1 week prior to experimentation. Twenty‐four hours after surgery, gastric emptying was measured using scintigraphy, and the degree of intestinal inflammation was assessed. Finally, activation of brain regions was assessed using quantitative immunohistochemistry for c‐fos.

KEY RESULTS Intestinal manipulation induced inflammation of the manipulated intestine and significantly delayed gastric emptying, 24 h after surgery in saline‐treated animals. Semapimod significantly reduced this inflammation and improved gastric emptying. Vagotomy enhanced the inflammatory response induced by intestinal manipulation and abolished the anti‐inflammatory effect of semapimod. Semapimod but not saline induced a significant increase in c‐fos expression in the paraventricular nucleus, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve.

CONCLUSIONS AND IMPLICATIONS Our findings show that i.c.v. semapimod reduces manipulation‐induced intestinal inflammation and prevented post‐operative ileus. This anti‐inflammatory effect depends on central activation of the vagus nerve.
Diverse patterns of cyclooxygenase‐independent metalloproteinase gene regulation in human monocytes
Authors: Reel Buket , Sala‐Newby Graciela B , Huang Wei‐Chun , Newby Andrew C.
Published: March 2011

BACKGROUND AND PURPOSE Matrix metalloproteinase (MMP) production from monocyte/macrophages is implicated in matrix remodelling and modulation of inflammation. However, knowledge of the patterns and mechanisms of gene regulation of MMPs and their endogenous tissue inhibitors (TIMPs) is fragmentary. MMP up‐regulation may be a target for cyclooxygenase (COX) and prostaglandin (PG) receptor inhibition, but the extent and mechanisms of COX‐independent MMP up‐regulation are unclear.

EXPERIMENTAL APPROACH We studied MMP mRNA expression and selected protein levels in human peripheral blood monocytes before and after adhesion, upon stimulation with bacterial lipopolysaccharide (LPS), PGE2 or forskolin and after culturing with monocyte colony‐stimulating factor on plastic or human fibronectin for up to 7 days.

KEY RESULTS Monocyte adherence for 2 h transiently up‐regulated COX‐2, MMP‐1, MMP‐7 and MMP‐10 mRNAs, and persistently up‐regulated MMP‐2, MMP‐9, MMP‐14 and MMP‐19 mRNAs. LPS, PGE2 or forskolin selectively increased MMP‐1, MMP‐9, MMP‐10, MMP‐12 and MMP‐14 mRNAs. LPS increased PGE2 production through COX but up‐regulated MMP levels independently of COX. Differential dependence on inhibition of p42/44 and p38 mitogen‐activated protein kinases, c‐jun N‐terminal kinase and inhibitor of κB kinase2 paralleled the diverse patterns of MMP stimulation by LPS. Differentiation on plastic increased mRNA levels of MMP‐7, MMP‐9, MMP‐12 and MMP‐14 and TIMP‐2 and TIMP‐3 independently of COX; fibronectin accelerated MMP but not TIMP up‐regulation.

CONCLUSIONS AND IMPLICATIONS Adhesion, LPS stimulation and maturation of human monocytes lead to selective, COX‐independent MMP and TIMP gene regulation, which is a potential target for selective inhibition by signalling kinase inhibitors.
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

Lidocaine 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

Lysophospatidic 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

The 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

Chronic 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

In 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

The 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

Assessment 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

In 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

Chronic 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

We 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

Wounded 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.
Recalcitrant Palmoplantar Pustular Psoriasis Treated with Etanercept
Authors: FLORISTAN UXUA , FELTES ROSA , RAMÍREZ PALOMA , ALONSO MARIA LUISA , De LUCAS RAUL
Published: March 2011

Abstract:  We report a 10‐year‐old boy presenting with palmoplantar pustular psoriasis, resistant to topical and systemic treatments, who was successfully treated with subcutaneous etanercept (0.4 mg/kg) twice a week for 1 month. Maintenance therapy was extended for 18 months in combination with near ultraviolet light therapy without any adverse effect. Etanercept may be a safe and effective alternative for severe palmoplantar pustular psoriasis in children.
Systemic Contact Dermatitis to Nickel Present in Cocoa in 14‐Year‐Old Boy
Authors: KRECISZ BEATA , CHOMICZEWSKA DOROTA , KIEC‐SWIERCZYNSKA MARTA , KASZUBA ANDRZEJ
Published: March 2011

Abstract:  Systemic contact dermatitis can be elicited in nickel sensitive individuals by oral nickel exposure from food with high content of this metal, such as cocoa. We present a case report of a nonatopic teenager who developed allergic contact dermatitis due to nickel, cobalt, copper, and palladium, but exacerbations of skin lesions were mainly related to cocoa consumption.
Spitz Nevi Arising in Speckled Lentiginous Nevus: Clinical, Histologic, and Molecular Evaluation of Two Cases
Authors: Torti Dorothea C. , Brennick Jeoffry B. , Storm Craig A. , Dinulos James G.H.
Published: March 2011

Abstract:  Spitz nevi are small dome‐shaped nodules that sometimes arise in areas of preexisting hyperpigmentation, such as a speckled lentiginous nevus (nevus spilus), where they present a diagnostic dilemma. We report clinical, histopathological, and molecular findings of two cases of multiple Spitz nevi arising in a speckled lentiginous nevus. We used immunohistochemistry to assess expression of Ki‐67, epidermal growth factor receptor, vascular endothelial growth factor, and RelA in two cases of Spitz nevi arising in a speckled lentiginous nevus. We observed rare staining for the proliferative marker Ki‐67, but positive staining for the growth and antiapoptotic factors epidermal growth factor receptor, vascular endothelial growth factor, and RelA. Characterization of the molecular phenotype of Spitz nevi arising in speckled lentiginous nevi may provide a useful adjunct to long‐term monitoring in this rare but difficult clinical presentation.
Infant Clothing Snaps as a Potential Source of Nickel Exposure
Authors: JACOB SHARON E. , MATIZ CATALINA
Published: March 2011

Abstract:  Children’s clothes with metal snaps are a potential source of nickel exposure to consider in infants and very young children. Further more avoidance of this exposure may help prevent nickel sensitization.
Being a Black Woman Philosopher: Reflections on Founding the Collegium of Black Women Philosophers
Authors: Gines Kathryn T.
Published: March 2011

Although the American Philosophical Association has more than 11,000 members, there are still fewer than 125 Black philosophers in the United States, including fewer than thirty Black women holding a PhD in philosophy and working in a philosophy department in the academy.1The following is a “musing” about how I became one of them and how I have sought to create a positive philosophical space for all of us.
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

Most 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

Purpose:  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.
Predictors of Nosocomial Bloodstream Infections in Older Adults
Authors: Kaye Keith S. , Marchaim Dror , Chen Ting‐Yi , Chopra Teena , Anderson Deverick J. , Choi Yong , Sloane Richard , Schmader Kenneth E.
Published: March 2011

OBJECTIVES: To identify predictors and construct a prediction model for nosocomial bloodstream infection (BSI) in older adults.

DESIGN: Retrospective case–control study.

SETTING: Hospitals belonging to the Duke Infection Control Outreach Network.

PARTICIPANTS: Patients age 65 and older with a nosocomial BSI and matched uninfected controls.

MEASUREMENT: Multiple variables were captured and compared between groups. Independent predictors were identified using conditional logistic regression. A prediction model and score was constructed.

RESULTS: Eight hundred thirty cases were compared with 830 controls. Eighty‐one percent of nosocomial BSIs were catheter related (CRBSI). Methicillin‐resistant Staphylococcus aureus (MRSA) was the most common pathogen isolated (23%). Independent predictors of nosocomial BSI in older adults were male sex, obesity, low McCabe score on admission, presence of a central line at admission, gastrostomy at admission, recent surgery, and urinary incontinence. A prediction model score greater than 11 (total possible score 23) was predictive of infection.

CONCLUSION: MRSA is a common cause of CRBSI in older adults. Male sex, obesity, the presence of a central line, a gastrostomy tube, and urinary incontinence at the time of admission were independent predictors of BSI in hospitalized older adults. The prediction model constructed in this study should be validated prospectively in a different cohort.
Optimal Capital Allocation Principles
Authors: Dhaene Jan , Tsanakas Andreas , Valdez Emiliano A. , Vanduffel Steven
Published: March 2011

Abstract

This article develops a unifying framework for allocating the aggregate capital of a financial firm to its business units. The approach relies on an optimization argument, requiring that the weighted sum of measures for the deviations of the business unit's losses from their respective allocated capitals be minimized. The approach is fair insofar as it requires capital to be close to the risk that necessitates holding it. The approach is additionally very flexible in the sense that different forms of the objective function can reflect alternative definitions of corporate risk tolerance. Owing to this flexibility, the general framework reproduces several capital allocation methods that appear in the literature and allows for alternative interpretations and possible extensions.
The Growth and Stability of the Local Tax Revenue in Japan
Authors: ISHIDA KAZUYUKI
Published: March 2011

This paper estimates the elasticity of the local tax revenue in Japan and analyzes the growth and stability of the Japanese local tax system. The main estimated results are as follows. The growth taxes in the long run are the Individual Enterprise Tax and the Fixed Asset Tax. There are no stable taxes in the short run. The total amount of prefectural tax revenue is low growth in the long run and unstable in the short run. The total amount of municipal tax revenue is low growth in the long run and neutral in the short run. The total amount of the local tax revenue in the prefecture and the municipality does not have stability and growth.
Allometric Model Improves Scaling of Left Atrial Size in Obese Population: The Use of Body Weight Containing Variables Is Challenged
Authors: Yao Gui‐Hua , Vallurupalli Neelima , Cui Jiang , Hiser William L. , Cook James R. , Jiang Leng
Published: March 2011

Background: Scaling left atrial (LA) size remains a challenge. An allometric model using body weight (BW) as scaling variable was recently proposed. We sought to examine the performance of this model in an obese population. Methods: A total of 266 consecutive overweight (110) and obese subjects (class I, II, and III obese 81, 47, and 28, respectively) were studied; 46 normal subjects with normal body mass index (BMI) served as controls. LA dimension (LAD) was scaled to BW, body surface area (BSA), BMI and height, respectively, using both isometric and allometric models. Results: There were no significant differences in age, gender, or height among the five groups. The prevalence of comorbid conditions, wall thickness, E/E’ and LAD measures increased significantly with increasing weight group (P < 0.01–0.001). With the isometric model, LAD corrected by BW, BSA, and BMI significantly but paradoxically decreased across the groups (P < 0.05–0.001). With the allometric model, LAD overcorrection by BM, BSA, and BMI was improved, but remained in the class III obese group. In contrast, scaling LAD to height showed significant and graded increase across the five groups in accordance with the increases of BMI, E/E’ and the prevalence of comorbid conditions. Conclusion: All isometric models that correct LAD by BW or BW containing variables underestimate LA size in overweight and obese groups. The allometric model using height provides more consistent results and should be preferred to models using BW or BW containing variables in scaling LAD in obese population. (Echocardiography 2011;28:253‐260)
Supernormal Diastolic Function and Role of Left Atrial Myocardial Deformation Analysis by 2D Speckle Tracking Echocardiography in Elite Soccer Players
Authors: D’Ascenzi Flavio , Cameli Matteo , Zacà Valerio , Lisi Matteo , Santoro Amato , Causarano Andrea , Mondillo Sergio
Published: March 2011

Purpose: Top‐level training is associated with morphological and functional changes in the heart. Left atrial (LA) enlargement can be regarded as a physiologic adaptation to exercise conditioning. Athletes show an improvement in myocardial diastolic properties and supernormal left ventricular (LV) diastolic function. The aims of the study were to assess diastolic function by pulsed Doppler tissue imaging (DTI) and to analyze the role of LA in athletes by speckle tracking echocardiography (STE). Methods: Twenty‐three male elite soccer players underwent a complete echocardiographic analysis. Twenty‐six age‐matched healthy sedentary men were used as controls. Measured variables included LA indexed volumes, DTI of the LV, peak atrial longitudinal strain, and peak atrial contraction strain (PACS). Results: LA areas and indexed volumes were significantly higher in athletes (P < 0.001). Athletes had a higher peak E velocity (P < 0.001), a lower A peak (P < 0.01), and a higher peak E/A ratio (P < 0.0001); a higher Em peak (P < 0.001), a lower Am peak (P < 0.01), and a higher Em/Am ratio (P < 0.0001). Global PACS was lower in athletes compared with controls (P < 0.0001) and strongly correlated with mitral Am (r = 0.55; P < 0.0001), mitral Em (r =−0.41; P < 0.001), heart rate (r =−0.38; P < 0.01), and LA area (r = 0.18; P < 0.05). Conclusions: Athletes showed a shift in the pattern of ventricular filling period toward early diastole as seen through DTI analysis of the diastolic properties of LV and STE analysis of LA function. DTI is a useful tool to analyze the improved myocardial diastolic properties of athletes and STE may elucidate the role of LA in the context of athlete's heart remodeling. (Echocardiography 2011;28:320‐326)
Controlling the Formation of Hydroxyapatite Nanorods with Dendrimers
Authors: Tsiourvas Dimitris , Tsetsekou Athena , Kammenou Maria‐Izoldi , Boukos Nikos
Published: March 2011

A facile procedure to direct the formation of hydroxyapatite (HAP) in preference to all other calcium phosphate phases and control over nanoparticle size distribution and morphology, with potential application in biomedical implants, is reported. The synthesis is performed in the presence of amine terminated diaminobutane poly(propylene imine) dendrimer (DAB). Aqueous solutions of calcium, phosphate, and DAB were used at different calcium:DAB molar ratios, viz. 2:1, 1:1, and 1:2 and the resulting suspensions were either kept at room temperature or hydrothermally treated at 80°C for 16 h, or at 130°C for 6 h. The resulting nanomaterials were fully characterized in terms of their physicochemical properties by means of XRD, TEM, SEM, and FTIR. It was found that DAB affects nucleation and crystal growth, as, in all cases, nanorods of hexagonal HAP with homogeneous and narrow size distributions (with mean sizes ranging from 10 nm × 5 nm up to 81 nm × 22 nm depending on synthesis conditions) were obtained.
What do simple models reveal about the population dynamics of a cooperatively breeding species?
Authors: Bateman A. W. , Coulson T. , Clutton‐Brock T. H.
Published: March 2011

Research on cooperatively breeding species has shown that their population dynamics differ from those of conventional breeders. Populations of cooperators are structured into groups, and group‐level Allee effects are likely common. We assess the ability of phenomenological models, lacking explicit group structure, to describe population dynamics in cooperative meerkats Suricata suricatta, and we assess potential Allee effects at the population level. Using maximum likelihood model fitting and information theoretic model selection, applied to time series data from a wild meerkat population, we find simple models that incorporate rainfall and conventional density dependence to be the most parsimonious of the models considered. Detecting no population‐level Allee effect, we conclude that explicit consideration of population structure will be key to understanding the mechanisms behind population dynamics in cooperatively breeding species.
Automatic measurement of epidermal thickness from optical coherence tomography images using a new algorithm
Authors: Josse G. , George J. , Black D.
Published: March 2011

Background/purpose: Optical coherence tomography (OCT) is an imaging system that enables in vivo epidermal thickness (ET) measurement. In order to use OCT in large‐scale clinical studies, automatic algorithm detection of the dermo‐epidermal junction (DEJ) is needed. This may be difficult due to image noise from optical speckle, which requires specific image treatment procedures to reduce this. In the present work, a description of the position of the DEJ is given, and an algorithm for boundary detection is presented.

Methods: Twenty‐nine images were taken from the skin of normal healthy subjects, from five different body sites. Seven expert assessors were asked to trace the DEJ for ET measurement on each of the images. The variability between experts was compared with a new image processing method.

Results: Between‐expert variability was relatively low with a mean standard deviation of 3.4 μm. However, local positioning of the DEJ between experts was often different.

The described algorithm performed adequately on all images. ET was automatically measured with a precision of <5 μm compared with the experts on all sites studied except that of the back. Moreover, the local algorithm positioning was verified.

Conclusion: The new image processing method for measuring ET from OCT images significantly reduces calculation time for this parameter, and avoids user intervention. The main advantages of this are that data can be analyzed more rapidly and reproducibly in clinical trials.
Msx‐1 is suppressed in bisphosphonate‐exposed jaw bone analysis of bone turnover‐related cell signalling after bisphosphonate treatment
Authors: Wehrhan F , Hyckel P , Amann K , Ries J , Stockmann P , Schlegel KA , Neukam FW , Nkenke E
Published: March 2011

Oral Diseases (2011) 17, 433–442

Objectives:  Bone‐destructive disease treatments include bisphosphonates and antibodies against receptor activator for nuclear factor κB ligand (aRANKL). Osteonecrosis of the jaw (ONJ) is a side‐effect. Aetiopathology models failed to explain their restriction to the jaw. The osteoproliferative transcription factor Msx‐1 is expressed constitutively only in mature jaw bone. Msx‐1 expression might be impaired in bisphosphonate‐related ONJ. This study compared the expression of Msx‐1, Bone Morphogenetic Protein (BMP)‐2 and RANKL, in ONJ‐affected and healthy jaw bone.

Material and methods:  An automated immunohistochemistry‐based alkaline phosphatase‐anti‐alkaline phosphatase method was used on ONJ‐affected and healthy jaw bone samples (n = 20 each): cell‐number ratio (labelling index, Bonferroni adjustment). Real‐time RT‐PCR was performed to quantitatively compare Msx‐1, BMP‐2, RANKL and GAPDH mRNA levels.

Results:  Labelling indices were significantly lower for Msx‐1 (P < 0.03) and RANKL (P < 0.003) and significantly higher (P < 0.02) for BMP‐2 in ONJ compared with healthy bone. Expression was sevenfold lower (P < 0.03) for Msx‐1, 22‐fold lower (P < 0.001) for RANKL and eightfold higher (P < 0.02) for BMP‐2 in ONJ bone.

Conclusions:  Msx‐1, RANKL suppression and BMP‐2 induction were consistent with the bisphosphonate‐associated osteopetrosis and impaired bone remodelling in BP‐ and aRANKL‐induced ONJ. Msx‐1 suppression suggested a possible explanation of the exclusivity of ONJ in jaw bone. Functional analyses of Msx‐1‐ RANKL interaction during bone remodelling should be performed in the future.
Characterization and partial purification of a bacteriocin‐like substance produced by thermophilic Bacillus licheniformis H1 isolated from cow manure compost
Authors: ABDEL‐MOHSEIN Hosnia S , SASAKI Takako , TADA Chika , NAKAI Yutaka
Published: March 2011

The production and partial characterization of bacteriocin‐like substances (BLSs) produced by bacteria isolated from cow manure compost were investigated. Eight BLS producers, which exhibited inhibitory activity against pathogenic bacteria, were isolated from cow manure compost at different stages of the composting process. The pile temperature ranged from 9.1°C to 73.2°C. The BLSs showed thermostability, but the BLS producers were not thermostable except for the H1 producer. Thermophilic Bacillus licheniformis H1 was further characterized. The culture supernatant of B. licheniformis H1 exhibited antagonistic activity against various species of Gram‐positive bacteria such as Listeria monocytogenes ATCC19111 but not against Gram‐negative bacteria except Pseudomonas fluorescens ATCC11251. Inactivation of bacteriocin‐like activity by α‐chymotrypsin, trypsin, and papain was highly significant (P < 0.001). The BLS was found to be stable under a pH range from 3 to 9 and at temperatures up to 75°C for 60 min, but it lost activity after being autoclaved at 121°C for 15 min. The optimum production of BLS by B. licheniformis H1 was obtained at a temperature of 55°C. Sodium dodecyl sulfate – polyacrylamide electrophoresis analysis of concentrated partially purified supernatants collected after resting the bacterial cells at 55°C revealed a bacteriocin‐like protein with a molecular mass of approximately 3.5 kDa. This study is the first report of a BLS from thermophilic B. licheniformis with an animal compost origin.
Fermentation characteristics and microorganism composition of total mixed ration silage with local food by‐products in different seasons
Authors: CAO Yang , CAI Yimin , HIRAKUBO Tomomi , FUKUI Hiroyuki , MATSUYAMA Hiroki
Published: March 2011

Total mixed ration (TMR) silage in different seasons was prepared with apple refuse, orchardgrass hay, orchardgrass silage, corn silage and a commercial compound feed in Tohoku, Japan, and with tofu cake, brewers' grains, tall fescue hay, Sudangrass hay, timothy hay, alfalfa hay and a commercial compound feed in Shikoku, Japan, respectively, and their fermentation quality and microorganism composition were evaluated. In Tohoku, the TMR silage in spring, autumn and winter displayed poor quality, with pH value above 4.7, and the harmful microorganisms such as escherichia, yeasts and molds were detected even after 60 days of ensiling; but the TMR silage in summer was well preserved and the escherichia were too few to count after 7 days of ensiling. In Shikoku, the TMR silage in all seasons was well preserved, with low pH, high lactic acid contents, and escherichia, yeasts and molds were consistently at or below the detectable numbers after 7 days of ensiling. The results showed that the TMR silage could not produce sufficient lactic acid to improve silage quality under low‐temperature conditions. Therefore, it is necessary to develop preparation techniques of promoting the lactic acid fermentation for TMR silage in cold seasons.