bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decrease in oxidative phosphorylation yield in presence of butyrate in perfused liver isolated from fed rats
Authors: Gallis Jean-Louis , Tissier Pierre , Gin Henri , Beauvieux Marie-Christine 
Published: August 2007

Abstract

Background
Butyrate is the main nutrient for the colonocytes but the effect of the fraction reaching the liver is not totally known. A decrease in tissue ATP content and increase in respiration was previously demonstrated when livers were perfused with short-chain fatty acids (SCFA) such as butyrate, or octanoate.
In fed rats the oxidative phosphorylation yield was determined on the whole isolated liver perfused with butyrate in comparison with acetate and octoanoate (3 mmol/L). The rate of ATP synthesis was determined in the steady state by monitoring the rate of ATP loss after inhibition of (i) cytochrome oxidase (oxidative phosphorylation) with KCN (2.5 mmol/L) and (ii) glyceraldehyde 3-phosphate dehydrogenase (glycolysis) with IAA (0.5 mmol/L). The ATP flux, estimated by 31P Nuclear Magnetic Resonance, and the measured liver respiration allowed the ATP/O ratio to be determined.

Results
ATP turnover was significantly lower in the presence of butyrate (0.40 ± 0.10 μmoles/min.g, p = 0.001, n = 7) and octanoate (0.56 ± 0.10 μmoles/min.g, p = 0.01, n = 5) than in control (1.09 ± 0.13 μmoles/min.g, n = 7), whereas perfusion with acetate induced no significant decrease (0.76 ± 0.10 μmoles/min.g, n = 7). Mitochondrial oxygen consumption was unchanged in the presence of acetate (1.92 ± 0.16 vs 1.86 ± 0.16 for control) and significantly increased in the presence of butyrate (p = 0.02) and octanoate (p = 0.0004) (2.54 ± 0.18 and 3.04 ± 0.15 μmoles/min.g, respectively). The oxidative phosphorylation yield (ATP/O ratio) calculated in the whole liver was significantly lower with butyrate (0.07 ± 0.02, p = 0.0006) and octanoate (0.09 ± 0.02, p = 0.005) than in control (0.30 ± 0.05), whereas there was no significant change with acetate (0.20 ± 0.02).

Conclusion
Butyrate or octanoate decrease rather than increase the rate of ATP synthesis, resulting in a decrease in the apparent ATP/O ratio. Butyrate as a nutrient has the same effect as longer chain FA. An effect on the hepatic metabolism should be taken into account when large quantities of SCFA are directly used or obtained during therapeutic or nutritional strategies.
Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D): design of a randomized study of the efficacy of low-dose aspirin in the prevention of cardiovascular events in subjects with diabetes mellitus treated with statins
Authors: De Berardis Giorgia , Sacco Michele , Evangelista Virgilio , Filippi Alessandro , Giorda Carlo B , Tognoni Gianni , Valentini Umberto , Nicolucci Antonio ,   ACCEPT-D Study Group
Published: August 2007

Abstract

Background
Despite the high cardiovascular risk, evidence of efficacy of preventive strategies in individuals with diabetes is scant. In particular, recommendations on the use of aspirin in patients with diabetes mostly reflect an extrapolation from data deriving from other high risk populations. Furthermore, the putative additive effects of aspirin and statins in diabetes remain to be investigated. This aspect is of particular interest in the light of the existing debate regarding the need of multiple interventions to reduce total cardiovascular risk, which has also led to the proposal of a polypill. Aim of the study is to evaluate the efficacy of aspirin in the primary prevention of major cardiovascular events in diabetic patients candidate for treatment with statins. These preventive strategies will be evaluated on the top of the other strategies aimed at optimizing the care of diabetic patients in terms of metabolic control and control of the other cardiovascular risk factors.

Methods/Design
The ACCEPT-D is an open-label trial assessing whether 100 mg/daily of aspirin prevent cardiovascular events in patients without clinically manifest vascular disease and treated with simvastatin (starting dose 20 mg/die). Eligible patients will be randomly assigned to receive aspirin + simvastatin or simvastatin alone. Eligibility criteria: male and female individuals aged >=50 years with diagnosis of type 1 or type 2 diabetes, already on treatment with statins or candidate to start the treatment (LDL-cholesterol >=100 mg/dL persisting after 3 months of dietary advise). The primary combined end-point will include cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospital admission for cardiovascular causes (acute coronary syndrome, transient ischemic attack, not planned revascularization procedures, peripheral vascular disease). A total of 515 first events are needed to detect a reduction in the risk of major cardiovascular events of 25% (alpha = 0.05; 1-beta = 0.90). Overall, 5170 patients will be enrolled. The study will be conducted by diabetes specialists and general practitioners.

Discussion
The study will provide important information regarding the preventive role of aspirin in diabetes when used on the top of the other strategies aimed to control cardiovascular risk factors.

Trial registration
Current Controlled Trials ISRCTN48110081.
Experimental transmission of atypical scrapie to sheep
Authors: Simmons Marion M , Konold Timm , Simmons Hugh A , Spencer Yvonne I , Lockey Richard , Spiropoulos John , Everitt Sharon , Clifford Derek 
Published: August 2007

Abstract

Background
Active surveillance for transmissible spongiform encephalopathies in small ruminants has been an EU regulatory requirement since 2002. A number of European countries have subsequently reported cases of atypical scrapie, similar to previously published cases from Norway, which have pathological and molecular features distinct from classical scrapie. Most cases have occurred singly in flocks, associated with genotypes considered to be more resistant to classical disease. Experimental transmissibility of such isolates has been reported in certain ovinised transgenic mice, but has not previously been reported in the natural host. Information on the transmissibility of this agent is vital to ensuring that disease control measures are effective and proportionate.

Results
This report presents the successful experimental transmission, in 378 days, of atypical scrapie to a recipient sheep of homologous genotype with preservation of the pathological and molecular characteristics of the donor. This isolate also transmitted to ovinised transgenic mice (Tg338) with a murine phenotype indistinguishable from that of Nor 98.

Conclusion
This result strengthens the opinion that these cases result from a distinct strain of scrapie agent, which is potentially transmissible in the natural host under field conditions.
Usefulness of open lung biopsy in mechanically ventilated patients with undiagnosed diffuse pulmonary infiltrates: influence of comorbidities and organ dysfunction
Authors: Lim Seong Yong , Suh Gee Young , Choi Jae Chol , Koh Won Jung , Lim Si Young , Han Joungho , Lee Kyung Soo , Shim Young Mog , Chung Man Pyo , Kim Hojoong , Kwon O Jung 
Published: August 2007

Abstract
Background
The purpose of this study was to evaluate the clinical usefulness of open lung biopsy (OLB) in patients undergoing mechanical ventilation for diffuse pulmonary infiltrates of unknown etiology.

Methods
This was a 10-year retrospective study in a 10-bed medical intensive care unit. The medical records of 36 ventilator-dependent patients who underwent OLB for the diagnosis of unknown pulmonary infiltrates from 1994 to 2004 were reviewed retrospectively. Data analyzed included demographic data, Charlson age–comorbidity score, number of organ dysfunctions, Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA) score, ventilation variables, and radiological patterns. Diagnostic yield, effect on subsequent treatment changes, and complications of OLB were also assessed.

Results
A specific clinico-pathologic diagnosis was obtained for 31 patients (86%). The most common diagnoses were interstitial pneumonia (n = 17, including 8 acute interstitial pneumonia) and viral pneumonia (n = 4). Therapeutic modifications were made in 64% of patients. Patients who received OLB less than 1 week after initiation of mechanical ventilation were more likely to survive (63% versus 11%; P = 0.018). There were no major complications associated with the procedure. Factors independently associated with survival were the Charlson age-comorbidity score, number of organ dysfunction and the PaO2/FiO2 ratio on the day of the OLB.

Conclusion
OLB can provide a specific diagnosis in many ventilator-dependent patients with undiagnosed pulmonary infiltrate. Early OLB seems to be useful in critically ill patients with isolated respiratory failure.
Comorbidity and Disease Status–Based Risk Stratification of Outcomes Among Patients With Acute Myeloid Leukemia or Myelodysplasia Receiving Allogeneic Hematopoietic Cell Transplantation
Authors: Sorror Mohamed L. , Sandmaier Brenda M. , Storer Barry E. , Maris Michael B. , Baron Frédéric , Maloney David G. , Scott Bart L. , Deeg H. Joachim , Appelbaum Frederick R. , Storb Rainer 
Published: August 2007

Purpose Retrospective studies have shown similar survival among patients with acute myeloid leukemia (AML) and myelodysplasia (MDS) after nonmyeloablative compared with myeloablative conditioning. Refined risk stratification is required to design prospective trials. Patients and Methods We stratified outcomes among patients with AML (n = 391) or MDS (n = 186) who received either nonmyeloablative (n = 125) or myeloablative (n = 452) allogeneic hematopoietic cell transplantation (HCT) based on comorbidities, as assessed by a HCT-specific comorbidity index (HCT-CI), as well as disease status. Patients receiving nonmyeloablative conditioning were older, more frequently pretreated, more often received unrelated grafts, and more often had HCT-CI scores of ≥ 3 compared with patients who received myeloablative conditioning. Results Patients with HCT-CI scores of 0 to 2 and either low or high disease risks had probabilities of overall survival at 2 years of 70% and 57% after nonmyeloablative conditioning compared with 78% and 50% after myeloablative conditioning, respectively. Patients with HCT-CI scores of ≥ 3 and either low or high disease risks had probabilities of overall survival of 41% and 29% with nonmyeloablative conditioning compared with 45% and 24% with myeloablative regimens, respectively. After adjusting for pretransplantation differences, stratified outcomes were not significantly different among patients receiving nonmyeloablative compared with myeloablative conditioning, with the exception of lessened nonrelapse mortality (hazard ratio, 0.50; P = .05) in the highest risk group. Conclusion Patients with low comorbidity scores could be candidates for prospective randomized trials comparing nonmyeloablative and myeloablative conditioning regardless of disease status. Additional data are required for patients with low-risk diseases and high comorbidity scores. Novel antitumor agents combined with nonmyeloablative HCT should be explored among patients with high comorbidity scores and advanced disease.
Two-Stage Robust Network Flow and Design Under Demand Uncertainty
Authors: Atamtürk Alper , Zhang Muhong 
Published: August 2007

We describe a two-stage robust optimization approach for solving network flow and design problems with uncertain demand. In two-stage network optimization, one defers a subset of the flow decisions until after the realization of the uncertain demand. Availability of such a recourse action allows one to come up with less conservative solutions compared to single-stage optimization. However, this advantage often comes at a price: two-stage optimization is, in general, significantly harder than single-stage optimization. For network flow and design under demand uncertainty, we give a characterization of the first-stage robust decisions with an exponential number of constraints and prove that the corresponding separation problem is 𝒩𝒫-hard even for a network flow problem on a bipartite graph. We show, however, that if the second-stage network topology is totally ordered or an arborescence, then the separation problem is tractable. Unlike single-stage robust optimization under demand uncertainty, two-stage robust optimization allows one to control conservatism of the solutions by means of an allowed “budget for demand uncertainty.” Using a budget of uncertainty, we provide an upper bound on the probability of infeasibility of a robust solution for a random demand vector. We generalize the approach to multicommodity network flow and design, and give applications to lot-sizing and location-transportation problems. By projecting out second-stage flow variables, we define an upper bounding problem for the two-stage min-max-min optimization problem. Finally, we present computational results comparing the proposed two-stage robust optimization approach with single-stage robust optimization as well as scenario-based two-stage stochastic optimization.
Fracture Incidence in GH-Deficient Patients on Complete Hormone Replacement Including GH
Authors: Holmer Helene , Svensson Johan , Rylander Lars , Johannsson Gudmundur , Rosén Thord , Bengtsson Bengt-Åke , Thorén Marja , Höybye Charlotte , Degerblad Marie , Bramnert Margareta , Hägg Erik , Engström Britt Edén , Ekman Bertil , Thorngren Karl-Göran , Hagmar Lars , Erfurth Eva-Marie 
Published: August 2007

Abstract
Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men.
Introduction: The objective of this study was to evaluate fracture incidence in patients with confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account.
Materials and Methods: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively.
Results: A more than doubled risk (IRR, 2.29; 95% CI, 1.23–4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR, 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI, 0.34–0.86) was recorded in AO GHD men.
Conclusions: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH–IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.
Development of a True Triaxial Apparatus for Sands and Gravels
Authors: Choi Changho , Arduino Pedro , Harney Michael D. 
Published: August 2007

AbstractThis paper presents a recently developed true triaxial apparatus and a series of verification studies. The apparatus is capable of handling 241-mm cubical specimens providing the means for testing specimens under a wide variety of stress paths under drained and undrained conditions. It uses flexible boundaries to apply three independently controlled principal stresses with back pressure. The apparatus also uses a fully computer-controlled electro-pneumatic loading system with advanced technology for data control. A testing program is presented for the purpose of verification. Pea-gravel specimens with D50=6.6 mm were tested under fully stress-controlled loading conditions. Stress paths used in this verification study include undrained and drained constant total mean stress paths and conventional triaxial compression and extension stress paths. Results from this study indicate that the newly developed apparatus is capable of capturing the stress-strain characteristics of coarse-grained soils.
Proteolytic Degradation of VE-Cadherin Alters the Blood-Retinal Barrier in Diabetes
Authors: Navaratna Deepti , McGuire Paul G. , Menicucci Gina , Das Arup 
Published: August 2007

OBJECTIVE— Increased vascular permeability due to alteration of the blood-retinal barrier (BRB) is one of the major complications in early diabetes. The aim of the present study was to determine whether diabetes alters the cellular expression and distribution of the adherens junction protein vascular endothelial (VE)-cadherin in retinal endothelial cells and if this alteration is mediated by proteinase activity.
RESEARCH DESIGN AND METHODS— Diabetes was induced in Brown Norway rats using streptozotocin, and retinal vascular permeability was measured by the Evans blue technique. The expression of matrix metalloproteinases (MMPs) and VE-cadherin was examined in isolated retinal vessels or cultured endothelial cells in response to diabetes and advanced glycation end products (AGEs). The cleavage of VE-cadherin from the endothelial cell surface was monitored by Western blotting following MMP or AGE treatment.
RESULTS— Retinal vascular permeability was significantly increased in rats following 2 weeks of diabetes coincident with a decrease of VE-cadherin expression. This increased vascular permeability could be inhibited with an MMP inhibitor. Treatment of endothelial cells with AGE-BSA led to a reduction of VE-cadherin staining on the cell surface and increased permeability, which was MMP mediated. Treatment of cells with specific MMPs or AGEs resulted in cleavage of VE-cadherin from the cell surface.
CONCLUSIONS— These observations suggest a possible mechanism by which diabetes contributes to BRB breakdown through proteolytic degradation of VE-cadherin. This may indicate a role for extracellular proteinases in alteration of the BRB seen in diabetic retinopathy.
Neuregulins Increase Mitochondrial Oxidative Capacity and Insulin Sensitivity in Skeletal Muscle Cells
Authors: Cantó Carles , Pich Sara , Paz José C. , Sanches Rosario , Martínez Vicente , Orpinell Meritxell , Palacín Manuel , Zorzano Antonio , Gumà Anna 
Published: August 2007

OBJECTIVE—Neuregulins are growth factors that are essential for myogenesis and regulate muscle metabolism. The addition of a recombinant neuregulin-1 isoform, heregulin-β1177–244 (Hrg), containing 3 nmol/l of the bioactive epidermal growth factor–like domain, to developing L6E9 myocytes has acute and chronic effects on glucose uptake and enhances myogenesis. Here, we studied the metabolic adaptation of myocytes to chronic treatments with Hrg.
RESEARCH DESIGN AND METHODS—L6E9 and C2C12 myocytes were chronically treated with low concentrations of Hrg (3 pmol/l) that do not induce myogenesis. We analyzed the effects of Hrg on cellular oxidative metabolism and insulin sensitivity and explored the mechanisms of action.
RESULTS—Hrg increased the cell content of GLUT4 without affecting basal glucose uptake. Glucose and palmitate oxidation increased in Hrg-treated cells, whereas lactate release decreased. Hrg increased the abundance of oxidative phosphorylation (OXPHOS) subunits, enhanced mitochondrial membrane potential, and induced the expression of peroxisome proliferator–activated receptor (PPAR)γ coactivator1α and PPARδ. Furthermore, we identified PPARδ as an essential mediator of the stimulatory effects of Hrg on the expression of OXPHOS subunits. The higher oxidative capacity of L6E9 myotubes after neuregulin treatment also paralleled an increase in insulin sensitivity and insulin signaling potency.
CONCLUSIONS—These results indicate that neuregulins act as key modulators of oxidative capacity and insulin sensitivity in muscle cells.
Alcohol Consumption and Type 2 Diabetes
Authors: Beulens Joline W.J. , Rimm Eric B. , Hendriks Henk F.J. , Hu Frank B. , Manson JoAnn E. , Hunter David J. , Mukamal Kenneth J. 
Published: August 2007

OBJECTIVE— We sought to investigate whether a polymorphism in the alcohol dehydrogenase 1c (ADH1C) gene modifies the association between alcohol consumption and type 2 diabetes.
RESEARCH DESIGN AND METHODS— In nested case-control studies of 640 women with incident diabetes and 1,000 control subjects from the Nurses’ Health Study and 383 men with incident diabetes and 382 control subjects from the Health Professionals Follow-Up Study, we determined associations between the ADH1C polymorphism, alcohol consumption, and diabetes risk.
RESULTS— Moderate to heavy alcohol consumption (&gt;5 g/day for women and &gt;10 g/day for men) was associated with a decreased risk of diabetes among women (odds ratio [OR] 0.45 [95% CI 0.33–0.63]) but not men (1.08 [0.67–1.75]). ADH1C genotype modified the relation between alcohol consumption and diabetes for women (Pinteraction = 0.02). The number of ADH1C*2 alleles, related to a slower rate of ethanol oxidation, attenuated the lower risk of diabetes among women consuming ≥5 g alcohol/day (Ptrend = 0.002). These results were not significant among men. Results were similar in pooled analyses (Pinteraction = 0.02) with ORs for diabetes among moderate drinkers of 0.44 (95% CI 0.21–0.94) in ADH1C*1 homozygotes, 0.65 (0.39–1.06) for heterozygotes, and 0.78 (0.50–1.22) for ADH1C*2 homozygotes compared with those for ADH1C*1 homozygote abstainers (Ptrend = 0.02).
CONCLUSIONS— ADH1C genotype modifies the association between alcohol consumption and diabetes. The ADH1C*2 allele, related to a slower oxidation rate, attenuates the lower diabetes risk among moderate to heavy drinkers. This suggests that the association between alcohol consumption and diabetes may be causal but mediated by downstream metabolites such as acetate rather than ethanol itself.
Physiological Hyperinsulinemia Has No Detectable Effect on Access of Macromolecules to Insulin-Sensitive Tissues in Healthy Humans
Authors: Weinhandl Heinz , Pachler Christoph , Mader Julia K. , Ikeoka Dimas , Mautner Agnes , Falk Andreas , Suppan Maria , Pieber Thomas R. , Ellmerer Martin 
Published: August 2007

OBJECTIVE—Physiologically elevated insulin concentrations promote access of macromolecules to skeletal muscle in dogs. We investigated whether insulin has a stimulating effect on the access of macromolecules to insulin-sensitive tissues in humans as well.RESEARCH DESIGN AND METHODS—In a randomized, controlled trial, euglycemic-hyperinsulinemic clamp (1.2 mU · kg−1 · min−1 insulin) and saline control experiments were performed in 10 healthy volunteers (aged 27.5 ± 4 years, BMI 22.6 ± 1.6 kg/m2). Distribution and clearance parameters of inulin were determined in a whole-body approach, combining primed intravenous infusion of inulin with compartment modeling. Inulin kinetics were measured in serum using open-flow microperfusion in interstitial fluid of femoral skeletal muscle and subcutaneous adipose tissue.RESULTS—Inulin kinetics in serum were best described using a three-compartment model incorporating a serum and a fast and a slow equilibrating compartment. Inulin kinetics in interstitial fluid of peripheral insulin-sensitive tissues were best represented by the slow equilibrating compartment. Serum and interstitial fluid inulin kinetics were comparable between the insulin and saline groups. Qualitative analysis of inulin kinetics was confirmed by model-derived distribution and clearance parameters of inulin. Physiological hyperinsulinemia (473 ± 6 vs. 18 ± 2 pmol/l for the insulin and saline group, respectively; P &lt; 0.001) indicated no effect on distribution volume (98.2 ± 6.2 vs. 102.5 ± 5.7 ml/kg; NS) or exchange parameter (217.6 ± 34.2 vs. 243.1 ± 28.6 ml/min; NS) of inulin to peripheral insulin-sensitive tissues. All other parameters identified by the model were also comparable between the groups.CONCLUSIONS—Our data suggest that in contrast to studies performed in dogs, insulin at physiological concentrations does not augment recruitment of insulin-sensitive tissues in healthy humans.