bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thoracic epidural anesthesia time-dependently modulates pulmonary endothelial dysfunction in septic rats
Authors: Lauer Stefan , Freise Hendrik , Westphal Martin , Zarbock Alexander , Fobker Manfred , Van Aken Hugo K , Sielenkämper Andreas W , Fischer Lars G 
Published: July 2009

Abstract
Introduction
Increasing evidence indicates that epidural anesthesia improves postoperative pulmonary function. The underlying mechanisms, however, remain to be determined. Because pulmonary nitric oxide has been identified to play a critical role in pulmonary dysfunction in sepsis, we hypothesized that thoracic epidural anesthesia (TEA) modulates endothelial dysfunction via a nitric oxide-dependent pathway.

Methods
Thirty-six Sprague-Dawley rats underwent sham laparotomy or induction of peritoneal sepsis caused by cecal ligation and puncture (CLP). Septic animals were then treated with either bupivacaine 0.5% or normal saline epidurally (15 μl/h-1) for 6 hours or 24 hours after injury. Previous experiments demonstrated that these time points correspond with a hyperdynamic (at 6 hours) and hypodynamic circulation (at 24 hours), respectively. In addition, two sham control groups received either bupivacaine 0.5% or normal saline epidurally (15 μl/h-1). Six and 24 hours after injury, hemodynamic measurements and arterial blood gas analyses were performed in awake, spontaneously breathing rats. Exhaled nitric oxide, bradykinin-induced pulmonary vasoconstriction (a surrogate marker of endothelial dysfunction), pulmonary wet/dry-weight ratio (an estimate of pulmonary edema), and myeloperoxidase activity (MPO, a surrogate marker of neutrophil infiltration into lung tisssue) were investigated at 6 and 24 hours by using an established model of isolated and perfused lungs.

Results
In hyperdynamic sepsis, treatment with TEA resulted in reduced bradykinin-induced pulmonary vasoconstriction (P < 0.05) and lower levels of exhaled NO as compared with those in untreated septic rats (P < 0.05). However, the development of pulmonary edema or MPO activity in the lungs was not alleviated by sympathetic blockade in this phase of sepsis. Conversely, TEA led to an increased bradykinin-induced pulmonary vasoconstriction and pulmonary edema despite reduced exNO levels and pulmonary MPO activity in hypodynamic sepsis (each P < 0.05 versus CLP 24 h). Pulmonary gas exchange was only marginally affected under the influence of TEA in hypodynamic sepsis. Mean arterial pressure and heart rate were not affected beyond the changes caused by sepsis itself.

Conclusions
The results of the present study suggest that TEA modulates the NO pathway and exerts positive effects on pulmonary endothelial integrity only in hyperdynamic sepsis. Whether the negative effects on endothelial function in hypodynamic sepsis have an impact on overall morbidity and mortality remains to be determined in future studies.
The relation between the incidence of hypernatremia and mortality in patients with severe traumatic brain injury
Authors: Maggiore Umberto , Picetti Edoardo , Antonucci Elio , Parenti Elisabetta , Regolisti Giuseppe , Mergoni Mario , Vezzani Antonella , Cabassi Aderville , Fiaccadori Enrico 
Published: July 2009

Abstract
Introduction
The study was aimed at verifying whether the occurrence of hypernatremia during the intensive care unit (ICU) stay increases the risk of death in patients with severe traumatic brain injury (TBI). We performed a retrospective study on a prospectively collected database including all patients consecutively admitted over a 3-year period with a diagnosis of TBI (post-resuscitation Glasgow Coma Score ≤ 8) to a general/neurotrauma ICU of a university hospital, providing critical care services in a catchment area of about 1,200,000 inhabitants.

Methods
Demographic, clinical, and ICU laboratory data were prospectively collected; serum sodium was assessed an average of three times per day. Hypernatremia was defined as two daily values of serum sodium above 145 mmol/l. The major outcome was death in the ICU after 14 days. Cox proportional-hazards regression models were used, with time-dependent variates designed to reflect exposure over time during the ICU stay: hypernatremia, desmopressin acetate (DDAVP) administration as a surrogate marker for the presence of central diabetes insipidus, and urinary output. The same models were adjusted for potential confounding factors.

Results
We included in the study 130 TBI patients (mean age 52 years (standard deviation 23); males 74%; median Glasgow Coma Score 3 (range 3 to 8); mean Simplified Acute Physiology Score II 50 (standard deviation 15)); all were mechanically ventilated; 35 (26.9%) died within 14 days after ICU admission. Hypernatremia was detected in 51.5% of the patients and in 15.9% of the 1,103 patient-day ICU follow-up. In most instances hypernatremia was mild (mean 150 mmol/l, interquartile range 148 to 152). The occurrence of hypernatremia was highest (P = 0.003) in patients with suspected central diabetes insipidus (25/130, 19.2%), a condition that was associated with increased severity of brain injury and ICU mortality. After adjustment for the baseline risk, the incidence of hypernatremia over the course of the ICU stay was significantly related with increased mortality (hazard ratio 3.00 (95% confidence interval: 1.34 to 6.51; P = 0.003)). However, DDAVP use modified this relation (P = 0.06), hypernatremia providing no additional prognostic information in the instances of suspected central diabetes insipidus.

Conclusions
Mild hypernatremia is associated with an increased risk of death in patients with severe TBI. In a proportion of the patients the association between hypernatremia and death is accounted for by the presence of central diabetes insipidus.
Insights into female sperm storage from the spermathecal fluid proteome of the honeybee Apis mellifera
Authors: Baer Boris , Eubel Holger , Taylor Nicolas L , O'Toole Nicholas , Millar A Harvey 
Published: July 2009

Abstract
Background
Female animals are often able to store sperm inside their body - in some species even for several decades. The molecular basis of how females keep non-own cells alive is largely unknown, but since sperm cells are reported to be transcriptionally silenced and, therefore, limited in their ability to maintain their own function, it is likely that females actively participate in sperm maintenance. Because female contributions are likely to be of central importance for sperm survival, molecular insights into the process offer opportunities to observe mechanisms through which females manipulate sperm.

Results
We used the honeybee, Apis mellifera, in which queens are highly polyandrous and able to maintain sperm viable for several years. We identified over a hundred proteins representing the major constituents of the spermathecal fluid, which females contribute to sperm in storage. We found that the gel profile of proteins from spermathecal fluid is very similar to the secretions of the spermathecal gland and concluded that the spermathecal glands are the main contributors to the spermathecal fluid proteome. A detailed analysis of the spermathecal fluid proteins indicate that they fall into a range of different functional groups, most notably enzymes of energy metabolism and antioxidant defense. A metabolic network analysis comparing the proteins detected in seminal fluid and spermathecal fluid showed a more integrated network is present in the spermathecal fluid that could facilitate long-term storage of sperm.

Conclusions
We present a large-scale identification of proteins in the spermathecal fluid of honeybee queens and provide insights into the molecular regulation of female sperm storage.
Secondary necrosis of apoptotic neutrophils induced by the human cathelicidin LL-37 is not proinflammatory to phagocytosing macrophages
Authors: Li Hsin-Ni , Barlow Peter G , Bylund Johan , Mackellar Annie , Björstad Åse , Conlon James , Hiemstra Pieter S , Haslett Chris , Gray Mohini , Simpson A John , Rossi Adriano G , Davidson Donald J 
Published: July 2009

Abstract
LL37-induced secondary necrosis of apoptotic neutrophils with release of granule contents potentiates the anti-inflammatory activity of apoptotic neutrophils on macrophages.
Cathelicidins are CHDP with essential roles in innate host defense but also more recently associated with the pathogenesis of certain chronic diseases. These peptides have microbicidal potential and the capacity to modulate innate immunity and inflammatory processes. PMN are key innate immune effector cells with pivotal roles in defense against infection. The appropriate regulation of PMN function, death, and clearance is critical to innate immunity, and dysregulation is implicated in disease pathogenesis. The efferocytosis of apoptotic PMN, in contrast to necrotic cells, is proposed to promote the resolution of inflammation. We demonstrate that the human cathelicidin LL-37 induced rapid secondary necrosis of apoptotic human PMN and identify an essential minimal region of LL-37 required for this activity. Using these LL-37-induced secondary necrotic PMN, we characterize the consequence for macrophage inflammatory responses. LL-37-induced secondary necrosis did not inhibit PMN ingestion by monocyte-derived macrophages and in contrast to expectation, was not proinflammatory. Furthermore, the anti-inflammatory effects of apoptotic PMN on activated macrophages were retained and even potentiated after LL-37-induced secondary necrosis. However, this process of secondary necrosis did induce the release of potentially harmful PMN granule contents. Thus, we suggest that LL-37 can be a potent inducer of PMN secondary necrosis during inflammation without promoting macrophage inflammation but may mediate host damage through PMN granule content release under chronic or dysregulated conditions.
Nucleophosmin may act as an alarmin: implications for severe sepsis
Authors: Nawa Yuko , Kawahara Ko-ichi , Tancharoen Salunya , Meng Xiaojie , Sameshima Hisayo , Ito Takashi , Masuda Yoshiki , Imaizumi Hitoshi , Hashiguchi Teruto , Maruyama Ikuro 
Published: July 2009

Abstract
Nucleophosmin exerts potent biological activities that contribute to systemic inflammation.
NPM is a major nucleolar multifunctional protein involved in ribosome biogenesis, centrosome duplication, cell-cycle progression, apoptosis, cell differentiation, and sensing cellular stress. Alarmins are endogenous molecules released from activated cells and/or dying cells, which activate the immune system and cause severe damage to cells and tissue organs. In the present work, stimulation of cells with the alarmin-inducible molecule endotoxin, for 16 h, resulted in NPM release into the culture supernatants of RAW264.7 cells, a murine macrophage cell line. Extracellular NPM was detected in the ascites of the CLP model. NPM was translocated into the cytoplasm from the nucleus in LPS -stimulated RAW264.7 cells; furthermore, NPM was detected in the cytosols of infiltrated macrophages in the CLP model. rNPM induced release of proinflammatory cytokines, TNF-α, IL-6, and MCP-1, from RAW264.7 cells and increased the expression level of ICAM-1 in HUVECs. NPM induced the phosphorylation of MAPKs in RAW264.7 cells. Our data indicate that NPM may have potent biological activities that contribute to systemic inflammation. Further investigations of the role of NPM may lead to new therapies for patients with septic shock or other inflammatory diseases.
Phase III, Randomized Study of Gemcitabine and Oxaliplatin Versus Gemcitabine (fixed-dose rate infusion) Compared With Gemcitabine (30-minute infusion) in Patients With Pancreatic Carcinoma E6201: A Trial of the Eastern Cooperative Oncology Group
Authors: Poplin Elizabeth , Feng Yang , Berlin Jordan , Rothenberg Mace L. , Hochster Howard , Mitchell Edith , Alberts Steven , O'Dwyer Peter , Haller Daniel , Catalano Paul , Cella David , Benson Al Bowen 
Published: July 2009

PurposeSingle-agent gemcitabine (GEM) is standard treatment of metastatic pancreatic cancer. Fixed-dose rate (FDR) GEM and GEM plus oxaliplatin have shown promise in early clinical trials. E6201 was designed to compare overall survival (OS) of standard weekly GEM 1,000 mg/m2/30 minutes versus GEM FDR 1,500 mg/m2/150 minutes or GEM 1,000 mg/m2/100 minutes/day 1 plus oxaliplatin 100 mg/m2/day 2 every 14 days (GEMOX).MethodsThis trial included patients with metastatic or locally advanced pancreatic cancer, normal organ function, and performance status of 0 to 2. The study was designed to detect a 33% difference in median survival (hazard ratio [HR] ≤ 0.75 for either of the experimental arms) with 81% power while maintaining a significance level of 2.5% in a two-sided test for each of the two primary comparisons.ResultsEight hundred thirty-two patients were enrolled. The median survival and 1-year survival were 4.9 months (95% CI, 4.5 to 5.6) and 16% for GEM, 6.2 months (95% CI, 5.4 to 6.9), and 21% for GEM FDR (HR, 0.83; stratified log-rank P = .04), and 5.7 months (95% CI, 4.9 to 6.5) and 21% for GEMOX (HR, 0.88; stratified log-rank P = .22). Neither of these differences met the prespecified criteria for significance. Survival was 9.2 months for patients with locally advanced disease, and 5.4 months for those with metastatic disease. Grade 3/4 neutropenia and thrombocytopenia were greatest with GEM FDR. GEMOX caused higher rates of nausea, vomiting, and neuropathy.ConclusionNeither GEM FDR nor GEMOX resulted in substantially improved survival or symptom benefit over standard GEM in patients with advanced pancreatic cancer.
Hypothalamic Leptin Signaling Regulates Hepatic Insulin Sensitivity via a Neurocircuit Involving the Vagus Nerve
Authors: German Jonathan , Kim Francis , Schwartz Gary J. , Havel Peter J. , Rhodes Christopher J. , Schwartz Michael W. , Morton Gregory J. 
Published: July 2009

AbstractRecent evidence suggests that hormones such as insulin and leptin act in the hypothalamus to regulate energy balance and glucose metabolism. Here we show that in leptin receptor-deficient Koletsky (fak/fak) rats, adenovirally induced expression of leptin receptors in the area of the hypothalamic arcuate nucleus improved peripheral insulin sensitivity via enhanced suppression of hepatic glucose production, with no change of insulin-stimulated glucose uptake or disposal. This effect was associated with increased insulin signal transduction via phosphatidylinositol-3-OH kinase (as measured by pY-insulin receptor substrate-1 and pS-PKB/Akt) in liver, but not skeletal muscle, and with reduced hepatic expression of the gluconeogenic genes, glucose-6-phosphatase and phosphoenolpyruvate kinase. Moreover, the beneficial effects of hypothalamic leptin signaling on hepatic insulin sensitivity were blocked by selective hepatic vagotomy. We conclude that hypothalamic leptin action increases peripheral insulin sensitivity primarily via effects on the liver and that the mechanism underlying this effect is dependent on the hepatic branch of the vagus nerve.
Metformin Inhibits Aromatase via an Extracellular Signal-Regulated Kinase-Mediated Pathway
Authors: Rice Suman , Pellatt Laura , Ramanathan Kumaran , Whitehead Saffron Anne , Mason Helen Diane 
Published: July 2009

Abstract
Metformin treatment, now widely prescribed in polycystic ovary syndrome, is aimed at correcting the associated insulin resistance, but it has also been shown to directly inhibit ovarian steroidogenesis. The mechanisms, however, by which metformin inhibits estradiol production in human granulosa cells remains unknown. Granulosa luteal cells were incubted with metformin, insulin, or combined metformin and insulin treatment, and aromatase mRNA expression was quantified using real-time RT-PCR. Enzyme activity was assessed by the conversion of 3H-androstenedione to estrone and estradiol. Metformin’s effect on the expression of specific untranslated first exon aromatase promoters was analyzed using semiquantitative PCR. The involvement of MAPK kinase (MEK)/ERK pathway was investigated by immunoblotting for aromatase, phosphorylated, and total ERK-1,2 from cells cultured as above with/without the MEK inhibitor PD98059. Metformin significantly inhibited basal and insulin-stimulated aromatase mRNA expression, with parallel results from the aromatase activity assay and protein assessment. This suppression was via down-regulation of aromatase promoter II, I.3, and 1.4 expression and was reversed by the addition of PD98059. Involvement of the ERK signaling pathway was demonstrated by the significant increase in phosphorylated ERK-1,2 with the combined metformin and insulin treatment. We have shown for the first time in human granulosa cells that metformin signficantly attenuated basal and insulin-stimulated P450 aromatase mRNA expression and activity, via silencing of key promoters. This occurred by activation of MEK/ERK pathway, which negatively regulated aromatase production. This is an important consideration given metformin’s widespread use in polycystic ovary syndrome and may further support a possible therapeutic indication in estrogen-dependent breast tumors.
Convex subspace closure of the point shadow of an apartment of a spherical building
Authors: Kasikova Anna 
Published: July 2009

Abstract
Let Σ be the point-line truncation of an augmented J-Grassmann geometry of a spherical building B. We show that if |J| = 1, or if |J| ≥ 2 and some additional conditions hold, then the convex subspace closure in Σ of the point shadow of an apartment of B is the entire space Σ.
The center conjecture for equifacetal simplices
Authors: Edmonds Allan L. 
Published: July 2009

Abstract
An equifacetal simplex, in which all facets are congruent, has a unique center. The center conjecture states that a simplex that has a unique center must be equifacetal. A strong version of the conjecture is proved in dimensions at most six by showing that there is an explicit list of centers, defined for all simplices, whose coinciding implies the simplex is equifacetal. It remains an open problem whether the conjecture is true in dimensions greater than six.
Polarities of shift planes
Authors: Knarr Norbert , Stroppel Markus 
Published: July 2009

Abstract
We construct polarities for arbitrary shift planes and develop criteria for conjugacy under the normalizer of the shift group. Under suitable assumptions (in particular, for finite or compact planes) we construct all shift groups on a given plane, and our constructions yield all conjugacy classes of polarities. We show that a translation plane admits an orthogonal polarity if, and only if, it is a shift plane. The corresponding planes are exactly those that can be coordinatized by commutative semifields. The orthogonal polarities form a single conjugacy class. Finally, we construct examples of compact connected shift planes with more conjugacy classes of polarities than the corresponding classical planes.
Irradiation-Induced Hardening and Embrittlement of High-Cr ODS Ferritic Steels
Authors: Lee J. H. , Kasada R. , Cho H. S. , Kimura A. 
Published: July 2009

Abstract
The dependence of irradiation temperature, neutron dose, and Cr content on irradiation hardening and embrittlement has been investigated for oxide dispersion strengthened (ODS) ferritic steels irradiated from 290 to 600°C up to the maximum neutron dose of 0.75 dpa. Irradiation hardening and embrittlement of the materials strongly depend on the irradiation temperature. While neutron dose increases from 0.01 to 0.21 dpa, the ODS steels with Al show a saturation of irradiation hardening but the no-Al ODS steel has an increase in the hardening. The higher the Cr content, the more significant the irradiation hardening and embrittlement of ODS steels irradiated below 420°C. Interestingly, the ODS ferritic steels exposed to neutrons show little change of tensile elongation, compared to 9Cr JLF-1. Furthermore the ductile-brittle transition temperature (DBTT) shift of ODS steels increases with the increasing irradiation hardening, indicating that the increase of yield strength due to radiation induced hardening increases the DBTT and thus a reduction of hardening is effective to reduce the DBTT shift.
Final Results from the Crack Initiation and Arrest of Irradiated Steel Materials Project on Fracture Mechanical Assessments of Pre-Irradiated RPV Steels Used in German PWR
Authors: Hein H. , Keim E. , Schnabel H. , Seibert T. , Gundermann A. 
Published: July 2009

Abstract
Pre-irradiated original reactor pressure vessel (RPV) materials covering all four German pressurized water reactors (PWR) construction lines were tested in the Crack Initiation and Arrest of Irradiated Steel Materials program to create a database of fracture toughness and arrest values for neutron fluences beyond the end of life range. The new database comprises data from both unirradiated and irradiated RPV base and weld materials generated by tensile, Charpy-V impact, fracture toughness KJc, and crack arrest KIa tests. The test matrix consists of materials with optimized chemical composition and with high Copper or high Nickel content, respectively. Based on the generated and already existing data the RTNDT and the RTT0 (Master Curve) concepts are applied with specific view on reference temperatures, transition temperature shifts, and on possible correlations between the criteria used in both concepts. In this context the consequences of some influencing factors like type and chemical composition of the RPV steel, its manufacturing conditions, and the specimen type and size on the reference temperatures are discussed. Moreover, the test results are assessed with respect to the American Society of Mechanical Engineers (ASME) code and German Nuclear Safety Standards Commission safety standards. The crack arrest characteristics for these typical RPV materials are also determined in a twofold way by testing Compact Crack Arrest specimens and by evaluation of instrumented Charpy-V impact test data. The available results made a good point that crack arrest is a reliable phenomenon that doubtless exists. It is also shown that the obtained KIa data can be enveloped by applying the ASME KIc lower bound curve indexed by different reference temperatures. Finally, the results show that the used RPV materials are well designed in terms of material behavior under irradiated conditions and that optimized manufacture specifications are of great benefit particularly after long operation times.
Buchbesprechungen
Authors: Woldt Claudia 
Published: July 2009

Zusammenfassung
PÖPPEL, LUDMILA, The Rhetoric of Pravda Editorials: A Diachronic Study of a Political Genre. Stockholm: Stockholm University, 2007. 306 S. (Acta Universitatis Stockholmiensis; Stockholm Slavic Studios; 33) ISBN 978-91-85445-61-5