bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Dkk3 protein expression in platelets and megakaryocytes of patients with myeloproliferative neoplasms
Authors: Tzankov Alexandar , Kern Johann , Pircher Andreas , Hermann Martin , Ott Helmut-Werner , Gastl Günther , Medinger Michael , Untergasser Gerold , Gunsilius Eberhard 
Published: October 2010

SummaryDickkopf-3 (Dkk3) has been proposed as tumour suppressor gene and a marker for tumour blood vessels. We analysed the expression and function of Dkk3 in platelets and megakaryocytes from healthy controls and patients with BCR-ABL1-negative myeloproliferative neoplasms (MPN). Dkk3 protein and gene expression in platelets was compared with endothelial and other blood cell populations by ELISA, real-time PCR, and immunofluorescence. Moreover, megakaryocytes were isolated from bone marrow aspirates by CD61 microbeads. Immunohisto-chemical studies of Dkk3 expression were performed in essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF) and control reactive bone marrow cases (each n=10). Compared to all other blood cell populations platelets showed the highest concentration of Dkk3 protein (150 ± 19 ng/mg total protein). A strong DKK3 gene and protein expression was also observed in isolated megakaryocytes. Dkk3 co-localised with VEGF in α-granules of platelets and was released similar to VEGF upon stimulation. Addition of recombinant Dkk3 had no influence on blood coagulation (aPTT, INR) and platelet aggregation. Significantly more Dkk3+ megakaryocytes/mm2 could be found in bone marrow biopsies from patients with MPN (ET 40 ± 10, PV 31 ± 4, PMF 22 ± 3) than in controls (15 ± 3). The mean proportion of Dkk3+ megakaryocytes was increased in MPN as well (ET 83% ± 15%; PV 84% ± 12%; PMF 77% ± 8%) compared to controls (53% ± 11%). Dkk3+ megakaryocytes correlated with microvessel density in PV and PMF. We conclude that Dkk3 might be involved in the pathogenesis of MPN.
Hydrologic Effects of Urbanization and Climate Change on the Flint River Basin, Georgia
Authors: Viger Roland J. , Hay Lauren E. , Markstrom Steven L. , Jones John W. , Buell Gary R. 
Published: October 2010

AbstractThe potential effects of long-term urbanization and climate change on the freshwater resources of the Flint River basin were examined by using the Precipitation-Runoff Modeling System (PRMS). PRMS is a deterministic, distributed-parameter watershed model developed to evaluate the effects of various combinations of precipitation, temperature, and land cover on streamflow and multiple intermediate hydrologic states. Precipitation and temperature output from five general circulation models (GCMs) using one current and three future climate-change scenarios were statistically downscaled for input into PRMS. Projections of urbanization through 2050 derived for the Flint River basin by the Forecasting Scenarios of Future Land-Cover (FORE-SCE) land-cover change model were also used as input to PRMS. Comparison of the central tendency of streamflow simulated based on the three climate-change scenarios showed a slight decrease in overall streamflow relative to simulations under current conditions, mostly caused by decreases in the surface-runoff and groundwater components. The addition of information about forecasted urbanization of land surfaces to the hydrologic simulation mitigated the decreases in streamflow, mainly by increasing surface runoff.
Disease progression in multiple sclerosis: combining physicians’ and patients’ perspectives?
Authors: Kragt JJ , Nielsen JM , van der Linden FAH , Polman CH , Uitdehaag BMJ 
Published: October 2010

Background: To assess disease progression in multiple sclerosis (MS) several outcome measures are available. The interrelation of changes on different scales has not been studied extensively and the concept of combining scales has only recently been introduced in MS. Objective: To explore combining different clinical outcome measures in the evaluation of disease progression in MS. Methods: In 553 patients we studied the presence of relevant changes according to standard definitions on the Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (9HPT), Timed 25-Foot Walk (T25FW) and the Multiple Sclerosis Impact Scale (MSIS-29). We examined ‘exclusive worsening’ (worsening on one measure while not worsening on any other measure) and ‘opposing changes’ (worsening on one measure while improving on another measure). Finally, we investigated the impact of combining assessments. Results: Based on the EDSS alone, 140 patients progressed. However, almost twice as many (275) showed worsening on any of the clinical outcome measures. Exclusive worsening was observed in 37 patients on the EDSS, 13 on the 9HPT, 39 on the T25FW and 44 on the MSIS physical. Of all worsened patients 76 (28%) showed opposing changes, a phenomenon predominantly observed when combining physician-based and patient-derived outcome measures. Conclusion: When assessing disease progression in MS, sensitivity to change can be increased by combining different outcome measures. The added value is especially present when combining measures from different perspectives. However, further research is needed to evaluate the optimal way to combine outcome measures before implementing this strategy in clinical studies.
Assessment of Mean Platelet Volume of Pregnant Women with Gestational Diabetes Mellitus and Impaired Glucose Tolerance as a Marker of Future Cardiovascular Disease Risk
Authors: Köşüş Aydin , Köşüş Nermin , Duran Müzeyyen , Turhan Nilgün Öztürk 
Published: October 2010

Objective To assess the platelet count and mean platelet volume (MPV) of pregnant women with gestational diabetes mellitus (GDM) or gestational impaired glucose tolerance (GIGT) to find out whether GDM and GIGT are risk factors for future development of cardiovascular disease. Study design A 50-g oral glucose load (OGL) was administered to all participants and heamotologic parameters were studied at 24–28 gestational weeks. When plasma glucose ≥ 140 mg/dl (7.8 mmol/L) was measured following the OGL, a 100 g-3-h oral glucose tolerance test was undertaken. Results A significant difference was observed for MPV values between the GDM and normal OGL groups. Conclusion Presence of a high MPV in GDM could demonstrate an increase in the risk for current and future thrombotic complications.
Nrf2 and selenoproteins are essential for maintaining oxidative homeostasis in erythrocytes and protecting against hemolytic anemia
Authors: Kawatani Yukie , Suzuki Takafumi , Shimizu Ritsuko , Kelly Vincent P. , Yamamoto Masayuki 
Published: October 2010

AbstractReactive oxygen species (ROS) are highly destructive toward cellular macromolecules. However, moderate levels of ROS can contribute to normal cellular processes including signaling. Herein we evaluate the consequence of a pro-oxidant environment on hematopoietic homeostasis. The NF-E2 related factor 2 (Nrf2) transcription factor regulates genes related to ROS scavenging and detoxification. Nrf2 responds to altered cellular redox status, such as occurs with loss of antioxidant selenoproteins after deletion of the selenocysteine-tRNA gene (Trsp). Conditional knockout of the Trsp gene using Mx1-inducible Cre-recombinase leads to selenoprotein deficiency and anemia on a wild-type background, whereas Trsp:Nrf2 double deficiency dramatically exacerbates the anemia and increases intracellular hydrogen peroxide levels in erythroblasts. Results indicate that Nrf2 compensates for defective ROS scavenging when selenoproteins are lost from erythroid cells. We also observed thymus atrophy in single Trsp-conditional knockout mice, suggesting a requirement for selenoprotein function in T-cell differentiation within the thymus. Surprisingly, no changes were observed in the myelomonocytic or megakaryocytic populations. Therefore, our results show that selenoprotein activity and the Nrf2 gene battery are particularly important for oxidative homeostasis in erythrocytes and for the prevention of hemolytic anemia.
Genome-wide identification and evolution of ATP-binding cassette transporters in the ciliate Tetrahymena thermophila: A case of functional divergence in a multigene family
Authors: Xiong Jie , Feng Lifang , Yuan Dongxia , Fu Chengjie , Miao Wei 
Published: October 2010

AbstractBackgroundIn eukaryotes, ABC transporters that utilize the energy of ATP hydrolysis to expel cellular substrates into the environment are responsible for most of the efflux from cells. Many members of the superfamily of ABC transporters have been linked with resistance to multiple drugs or toxins. Owing to their medical and toxicological importance, members of the ABC superfamily have been studied in several model organisms and warrant examination in newly sequenced genomes.ResultsA total of 165 ABC transporter genes, constituting a highly expanded superfamily relative to its size in other eukaryotes, were identified in the macronuclear genome of the ciliateTetrahymena thermophila. Based on ortholog comparisons, phylogenetic topologies and intron characterizations, each highly expanded ABC transporter family ofT.thermophilawas classified into several distinct groups, and hypotheses about their evolutionary relationships are presented. A comprehensive microarray analysis revealed divergent expression patterns among the members of the ABC transporter superfamily during different states of physiology and development. Many of the relatively recently formed duplicate pairs within individual ABC transporter families exhibit significantly different expression patterns. Further analysis showed that multiple mechanisms have led to functional divergence that is responsible for the preservation of duplicated genes.ConclusionGene duplications have resulted in an extensive expansion of the superfamily of ABC transporters in theTetrahymenagenome, making it the largest example of its kind reported in any organism to date. Multiple independent duplications and subsequent divergence contributed to the formation of different families of ABC transporter genes. Many of the members within a gene family exhibit different expression patterns. The combination of gene duplication followed by both sequence divergence and acquisition of new patterns of expression likely plays a role in the adaptation ofTetrahymena to its environment.
Dissociation of μ- and δ-opioid Inhibition of Glutamatergic Synaptic Transmission in Superficial Dorsal Horn
Authors: Wrigley Paul J , Jeong Hyo-Jin , Vaughan Christopher W 
Published: October 2010

Background:There is anatomical and behavioural evidence that μ- and δ-opioid receptors modulate distinct nociceptive modalities within the superficial dorsal horn. The aim of the present study was to examine whether μ- and δ-opioid receptor activation differentially modulates TRP sensitive inputs to neurons within the superficial dorsal horn. To do this, whole cell patch clamp recordings were made from lamina I – II neurons in rat spinal cord slices in vitro to examine the effect of opioids on TRP agonist-enhanced glutamatergic spontaneous miniature excitatory postsynaptic currents (EPSCs).Results:Under basal conditions the μ-opioid agonist DAMGO (3 μM) reduced the rate of miniature EPSCs in 68% of neurons, while the δ- and κ-opioid agonists deltorphin-II (300 nM) and U69593 (300 nM) did so in 13 – 17% of neurons tested. The TRP agonists menthol (400 μM) and icilin (100 μM) both produced a Ca2+-dependent increase in miniature EPSC rate which was unaffected by the voltage dependent calcium channel (VDCC) blocker Cd2+. The proportion of neurons in which deltorphin-II reduced the miniature EPSC rate was enhanced in the presence of icilin (83%), but not menthol (0%). By contrast, the proportion of DAMGO and U69593 responders was unaltered in the presence of menthol (57%, 0%), or icilin (57%, 17%).Conclusions:These findings demonstrate that δ-opioid receptor activation selectively inhibits inputs activated by icilin, whereas μ-opioid receptor activation has a more widespread effect on synaptic inputs to neurons in the superficial dorsal horn. These findings suggest that δ-opioids may provide a novel analgesic approach for specific, TRPA1-like mediated pain modalities.
Bromocriptine Mesylate for Glycemic Management in Type 2 Diabetes Mellitus
Authors: Kerr Jessica L , Timpe Erin M , Petkewicz Katherine A 
Published: October 2010

Objective: To review the pharmacologic characteristics, safety, and efficacy of bromocriptine mesylate for glycemic control in patients with type 2 diabetes mellitus. Data Sources: A Scopus and MEDLINE search (1950–June 2010) was conducted using the key words bromocriptine, diabetes, and circadian rhythm. Data were also received from the manufacturer. Study Selection and Data Extraction: Available abstracts, studies, and review articles published in English with human data discussing bromocriptine treatment for type 2 diabetes mellitus were reviewed. Data Synthesis: Bromocriptine is an ergot derivative available for treatment of type 2 diabetes. The mechanism of action of this agent is unclear; however, activity as a dopamine D2 receptor agonist seems to provide the primary mechanism for utility in resetting the circadian rhythm in patients with type 2 diabetes. Other mechanisms, including α-1 antagonist, α-2 agonist, and serotonin and prolactin modulator, may also help to explain bromocriptine's glucose-lowering effects. Studies with bromocriptine have included 4328 patients with type 2 diabetes. The majority of available trials conducted enrolled patients for a study duration of 6–24 weeks. One trial evaluating the safety and efficacy of bromocriptine concluded after 52 weeks of follow-up. Endpoints of hemoglobin A1c (A1C) reduction and plasma glucose concentrations were the primary focus of all studies, with statistically significant differences found. Bromocriptine use resulted in a mean A1C reduction of 0.27% (range 0.1–0.6), while placebo resulted in a mean A1C increase of 0.48% (range 0.3–1.1), Incidence of adverse effects of nausea, vomiting, headache, and rhinitis was greater than that of placebo in clinical trials. Cardiovascular endpoints did not differ from those of placebo. Conclusions: Bromocriptine has demonstrated efficacy as an adjunctive agent in the management of type 2 diabetes. Caution may be warranted in the elderly population or patients at risk for suspected drug-drug interactions. Further studies of longer duration may help to define the role of bromocriptine in the management of diabetes.
Nicotine Replacement Therapy Effect on Pregnancy Outcomes
Authors: Forinash Alicia B , Pitlick Jamie M , Clark Kylie , Alstat Valerie 
Published: October 2010

Objective: To review data assessing the effects of nicotine replacement therapy (NRT) during pregnancy on fetal, neonatal, and maternal outcomes. Data Sources: A literature search of PubMed (1966-Jufy 2010) was performed using the terms smoking, smoking cessation, pregnancy, and nicotine replacement therapy. Bibliographies and the Cochrane Database were reviewed to identify additional relevant articles. Study Selection and Data Extraction: All studies including humans and published in English with data describing NRT effects on pregnancy outcomes or malformations as a primary or secondary outcome were evaluated. Data Synthesis: Currently, behavior modification therapy is recommended for smoking cessation in pregnancy as first-line treatment, but NRT should be offered to patients who are not successful. NRT is currently a pregnancy category D medication. Pregnancy outcomes and malformation rates for NRT in pregnancy were evaluated as either primary or secondary outcomes in several trials. Four studies examined pregnancy outcomes after a full course of nicotine gum or patch therapy. NRT use significantly decreased the risk of preterm delivery and low birth weight compared to that of smokers. Only 1 study evaluated the risk of malformations after exposure to the NRT patch during the first trimester. In a retrospective analysis, NRT users had an increased risk for any fetal malformation but not for major or musculoskeletal ones. However, no adjustments were made for many known factors associated with malformations. Conclusions: Behavior modification therapy should always be the first method tried for smoking cessation in the pregnant population. If behavior modification therapy is attempted without success, NRT should be offered because of decreased risk for low birth weight and preterm delivery compared to continued smoking. Additionally, NRT does not appear to increase the risk for malformations.
Antifungal activities of three supercritical fluid extracted cedar oils
Authors: Du Tianchuan , Shupe Todd F. , Hse Chung Y. 
Published: October 2010

Abstract
Port-Orford cedar (Chamaecyparis lawsoniana), Alaska yellow cedar (Chamaecyparis nootkatensis), and Eastern red cedar (Juniperus virginiana) were submitted to supercritical fluid extraction with CO2 (SCC) and Soxhlet extracted (SE) with hexane. The components in the extracted oils were identified by GC-MS. The oils were evaluated against two common wood decay fungi, brown-rot fungus (Gloeophyllum trabeum) and white-rot fungus (Trametes versicolor). The SCC extraction yields of J. virginiana, C. nootkatensis, and C. lawsoniana were 3.27%, 3.22%, and 3.29%, respectively. The SE yields of J. virginiana, C. nootkatensis, and C. lawsoniana were 0.80%, 0.71%, and 1.52%, respectively. The statistical analysis showed that SCC extracted cedar oils had higher antifungal activities than SE cedar oils against both fungi. In vitro studies showed that C. nootkatensis oils have the strongest antifungal activity, followed by C. lawsoniana, and J. virginiana oil.
Exendin-4 Suppresses Src Activation and Reactive Oxygen Species Production in Diabetic Goto-Kakizaki Rat Islets in an Epac-Dependent Manner
Authors: Mukai Eri , Fujimoto Shimpei , Sato Hiroki , Oneyama Chitose , Kominato Rieko , Sato Yuichi , Sasaki Mayumi , Nishi Yuichi , Okada Masato , Inagaki Nobuya 
Published: October 2010

OBJECTIVEReactive oxygen species (ROS) is one of most important factors in impaired metabolism secretion coupling in pancreatic β-cells. We recently reported that elevated ROS production and impaired ATP production at high glucose in diabetic Goto-Kakizaki (GK) rat islets are effectively ameliorated by Src inhibition, suggesting that Src activity is upregulated. In the present study, we investigated whether the glucagon-like peptide-1 signal regulates Src activity and ameliorates endogenous ROS production and ATP production in GK islets using exendin-4.RESEARCH DESIGN AND METHODSIsolated islets from GK and control Wistar rats were used for immunoblotting analyses and measurements of ROS production and ATP content. Src activity was examined by immunoprecipitation of islet lysates followed by immunoblotting. ROS production was measured with a fluorescent probe using dispersed islet cells.RESULTSExendin-4 significantly decreased phosphorylation of Src Tyr416, which indicates Src activation, in GK islets under 16.7 mmol/l glucose exposure. Glucose-induced ROS production (16.7 mmol/l) in GK islet cells was significantly decreased by coexposure of exendin-4 as well as PP2, a Src inhibitor. The Src kinase–negative mutant expression in GK islets significantly decreased ROS production induced by high glucose. Exendin-4, as well as PP2, significantly increased impaired ATP elevation by high glucose in GK islets. The decrease in ROS production by exendin-4 was not affected by H-89, a PKA inhibitor, and an Epac-specific cAMP analog (8CPT-2Me-cAMP) significantly decreased Src Tyr416 phosphorylation and ROS production.CONCLUSIONSExendin-4 decreases endogenous ROS production and increases ATP production in diabetic GK rat islets through suppression of Src activation, dependently on Epac.
Body and Liver Fat Mass Rather Than Muscle Mitochondrial Function Determine Glucose Metabolism in Women With a History of Gestational Diabetes Mellitus
Authors: Prikoszovich Thomas , Winzer Christine , Schmid Albrecht Ingo , Szendroedi Julia , Chmelik Marek , Pacini Giovanni , Krššák Martin , Moser Ewald , Funahashi Tohru , Waldhäusl Werner , Kautzky-Willer Alexandra , Roden Michael 
Published: October 2010

OBJECTIVE
Ectopic lipid storage in muscle (intramyocellular lipids [IMCL]) and liver (hepatocellular lipids [HCL]) coexists with impaired myocellular flux through ATP synthase (fATPase) in certain cohorts with increased risk of type 2 diabetes. Because women with a history of gestational diabetes mellitus (pGDM) have elevated ectopic lipids and diabetes risk, we tested whether deteriorated energy metabolism contributes to these abnormalities.

RESEARCH DESIGN AND METHODS
A total of 23 glucose-tolerant nonobese pGDM and eight women with normal glucose metabolism during pregnancy with similar age, body mass, and physical activity underwent oral glucose tolerance tests (OGTT) and intravenous glucose tolerance tests at 4–5 years after delivery. OGTT values &lt;463 mL ⋅ min−1 ⋅ m−2 were considered to indicate insulin resistance. pGDM were further stratified into insulin-resistant (pGDM-IR) and insulin-sensitive (pGDM-IS) groups. IMCL, HCL, and fATPase were measured with 1H/31P magnetic resonance spectroscopy.

RESULTS
pGDM had 36% higher fat mass and 12% lower insulin sensitivity. Log-transformed fATPase was lower in pGDM (10.6 ± 3.8 µmol ⋅ mL muscle−1 ⋅ min−1 vs. 12.1 ± 1.4 µmol ⋅ mL muscle−1 ⋅ min−1, P &lt; 0.03) and related to plasma adiponectin after adjustment for body fat (r = 0.44, P &lt; 0.04). IMCL were 61% and 69% higher in pGDM-IR (P &lt; 0.05 vs. pGDM-IS) and insulin resistant women (P &lt; 0.003 vs. insulin sensitive), respectively. HCL were doubled (P &lt; 0.05) in pGDM and insulin resistant women, and correlated positively with body fat mass (r = 0.50, P &lt; 0.01) and inversely with insulin sensitivity (r = −0.46, P &lt; 0.05).

CONCLUSIONS
Glucose-tolerant pGDM show increased liver fat but only slightly lower muscular insulin sensitivity and ATP synthesis. This suggests that alteration of hepatic lipid storage represents an early and predominant abnormality in this cohort.
Risk of Acute Complications of Diabetes Among People With Schizophrenia in Ontario, Canada
Authors: Becker Taryn , Hux Janet 
Published: October 2010

OBJECTIVE
Diabetes mellitus (DM) is a complex, chronic disease requiring active self-management and coordinated care. This study aimed to evaluate the relationship between schizophrenia and risk of preventable, acute DM complications.

RESEARCH DESIGN AND METHODS
With the use of administrative data, a retrospective study assessed acute DM complications (emergency department [ED] visits or hospitalization for hypo- or hyperglycemia and hospital admissions for infections) among Ontario residents ages 18–50 with schizophrenia and newly diagnosed DM between 1995 and 2005, comparing people with and without pre-existing schizophrenia. Primary outcome was ED visit or hospitalization for hypo- or hyperglycemia. Secondary outcome was the first of either the primary outcome or hospitalization for infection.

RESULTS
People with schizophrenia had a 74% greater risk of requiring a hospital visit for hypo- or hyperglycemia (hazard ratio [HR] = 1.74, 95% confidence interval 1.42–2.12) compared with those without schizophrenia. The risk was similar when the outcome included infection (HR = 1.62, 95% CI 1.39–1.89). Outcomes remained significant after adjustment for baseline characteristics.

CONCLUSIONS
People with schizophrenia are at greater risk for developing an acute complication of DM. Understanding this relationship will direct future studies assessing barriers to care and implementation of individualized approaches to care for this population.