bluuebunny/crossref_metadata_2025 huggingface dataset:
Compressible Streamline-Based Simulation With Changes in Oil Composition
Authors: Beraldo V. T. , Blunt M. J. , Schiozer D. J.
Published: November 2009

In Brazil, there are several offshore oil fields with horizontal oil-density variations. API tracking, which is available in some commercial finite difference simulators, can deal with such cases by allowing the definition of an initial oil-gravity distribution and tracking variations of oil density owing to the movement of oil.

Streamline-based simulators can be much faster than conventional finite-difference simulators when applied to large and heterogeneous models. However, this approach is most accurate and efficient when it is assumed that the rock and fluids are incompressible. In previous work, Beraldo et al. (2007) presented an incompressible formulation for streamline simulation with an API tracking option using two components in the oleic phase.

This paper presents a compressible formulation for streamlines that also considers API tracking. It has an approach similar to the one presented by Cheng et al. (2006) and Osako and Datta-Gupta (2007). However, cumulative volume is used in the streamline solution, instead of time of flight, which reduces mass-conservation errors.

The method was implemented in a 3D two-phase streamline-based simulator. Tests based on a Brazilian oilfield model demonstrate that the implementation can reproduce the results of a conventional simulator, even when significant liquid compressibilities are considered. Another test, using the SPE 10th Comparative Case, indicates that it can be substantially faster for finely resolved models.
Selecting sanitation systems for sustainability in developing countries
Authors: Flores A. , Buckley C. , Fenner R.
Published: November 2009

This paper presents a methodology for systematically incorporating multi-dimensional sustainability considerations into the selection of wastewater options for developing countries and the evaluation and comparison of these options. Appropriate technologies for developing countries were screened based on their function and their use of operational sustainability features; this list of technologies can then be used to elaborate design options. Sustainability indicators are used to enable a parallel comparison of the options from environmental, economic, and socio-cultural perspectives. For illustration, the indicator approach is applied to a case study of the sanitation options for peri-urban/rural areas of the eThekwini Municipality in South Africa.
Effect of anionic surfactants on the process of Fenton degradation of methyl orange
Authors: Yang C. W. , Wang D.
Published: November 2009

Fenton process has been shown to be very successful to remove dyes from water. However, the influence of other constituents in dyeing industry wastewater, such as Sodium Dodecyl Sulphate (SDS) surfactants, has not been investigated. In this study, the effect of SDS surfactant on the kinetics of Methyl Orange degradation undergoing Fenton process was investigated. Results show that Methyl Orange degradation rate decreased as SDS concentration increased, which was attributed to the consumption of hydroxyl radicals (∙OH) by surfactants and the formation of Methyl Orange-SDS complex. No evidence was found that the Methyl Orange degradation pathway was affected by the presence of SDS. The kinetics modelling indicates the reaction was the first-order reaction to Methyl Orange.
Viability of multiple antibiotic resistant bacteria in distribution lines of treated sewage effluent used for irrigation
Authors: Al-Bahry S. N. , Mahmoud I. Y. , Al-Khaifi A. , Elshafie A. E. , Al-Harthy A.
Published: November 2009

Viability of multiple antibiotic resistant bacteria (MARB) in tertiary treated sewage effluent (TTSE) used for irrigation, was investigated at the Sultan Qaboos University sewage treatment plant (STP). This water recycle system is used here as a model for the systems commonly used throughout Oman and the Gulf region. Samples of TTSE were collected weekly from four sites, 1.5 km from each other. Chlorine levels declined gradually at the three sites with increasing distance from the STP. Viable bacteria, coliforms and nitrate concentrations increased significantly while biological oxygen demand (BOD) declined after STP chlorination. Mean values of turbidity changed slightly. Trace elements values were insignificant. A total of 336 bacteria from 8 genera revealed that the dominant isolates were Enterobacter spp., Pseudomonas spp., and Aeromonas spp. Among the isolates 59.8% were multiply resistant to several antibiotics. Resistance was higher to ampicillin followed by sulphamethoxazole, carbenicillin, streptomycine and minocycline. Frequency of resistance to the 14 antibiotics varied among the isolates. The present system related to the viability of MARB in TTSE used for irrigation may have serious implications for public health and wildlife. Results of this investigation will be of value in modifying current STPs systems and thus avoiding serious health issues.
Comparison of partial nitrification to nitrite for ammonium-rich organic wastewater in sequencing batch reactors and continuous stirred-tank reactor at laboratory-scale
Authors: Yan J. , Hu Y. Y.
Published: November 2009

The combined partial nitrification/Anammox process is especially suitable for the treatment of influents with low C/N ratio. However, many nitrogenous wastewater are also rich in organics. Two systems (continuous stirred-tank reactor (CSTR) and sequencing batch reactor (SBR)) are commonly used to achieve nitrite accumulation, but no complete comparison between these two systems for treating different wastewater has been reported. The objective of this paper was to compare the partial nitrification in CSTR and SBR for the treatment of ammonium-rich organic wastewater. The result showed that it took a shorter time to startup partial nitrification in CSTR, but SBR was a better option for treating ammonium-rich organic wastewater with C/N lower than 0.34. With increase HRT to 48 h, excellent nitrite accumulation could be achieved in both reactors for wastewater containing landfill leachate. For subsequent anammox, CSTR was more suitable when leachate percentage ranged from 35% to 40%.
The application of wetland technology for copper removal from distillery wastewater: a case study
Authors: Murphy C. , Hawes P. , Cooper D. J.
Published: November 2009

The ability of reed beds to remove significant levels of metals from effluent streams is well cited in the literature. Various methods of removal have been postulated and demonstrated including physical methods such as filtration and settlement, precipitation when the metal is present as a salt and adsorption to organic species or take up by macrophytes when the metal is in a soluble or ionic form. Consequently, reed beds have been used in a variety of applications for metal removal in water treatment processes. The distillation process for whisky generates an effluent containing a significant amount of copper which is scoured from the copper stills during the process and cleaning operations. High soluble copper concentrations can breach discharge consents. A horizontal subsurface flow reed bed system has been designed and installed for copper removal at a distillery in Scotland. This paper presents the findings of the literature search, outlines the design of the bed and reviews the performance results.
Three Versus Seven-Day Treatment of Asymptomatic Bacteriuria in Pregnant Women: A Pilot Investigation
Authors: Mittal Pooja , Pan Vivien , Wing Deborah A.
Published: November 2009

Objective:

To compare 3-day vs 7-day antimicrobial treatment for asymptomatic bacteriuria in pregnant women
in a pilot study.

Methods:

Pregnant women with asymptomatic bacteriuria (100,000 cfu/mL) were randomized to 3-day or 7-day
nitrofurantoin treatment. Exclusion criteria included symptomatic bacteriuria at enrollment, previously treated bacteriuria
in the current pregnancy, underlying renal disorders, antibiotic use within one week prior to initial culture or treatment,
bacterial resistance to nitrofurantoin, or other contraindications to nitrofurantoin. Urine test of cure (TOC) was performed
2-4 weeks after initiation of treatment. Subjects with persistent bacteriuria received an additional 7-day treatment course
with an antimicrobial agent based on uropathogen sensitivities and selected at the physician’s discretion. Following
delivery, antenatal, perinatal, and neonatal data were reviewed. Statistical analyses were performed using t-test, Chisquare,
and Fisher exact where appropriate. Analysis was based on intent-to-treat.

Results:

Forty-four of 60 patients had complete prenatal and delivery records. Twenty-four patients (54.5%) were
randomized to 3-day treatment and 20 patients (45.5%) to 7-day treatment. Six (25%) patients in the 3-day group had
persistent bacteriuria at TOC, compared to 2 (10%) patients in the 7-day group (p=0.19). There were no statistical
differences between the groups in maternal age, gestational age at enrollment, mode of delivery, birth weight, NICU
admissions, or the incidence of recurrent urinary tract infections or pyelonephritis.

Conclusion:

Based on our small sample group, 3-day nitrofurantoin treatment had statistically comparable outcomes to 7-
day treatment for asymptomatic bacteriuria in pregnant patients, yet 3-day-treated women were 2.5 times more likely to
have persistent bacteriuria than 7-day-treated women. The possibility of a beta error exists. In light of recent data which
indicates that 1-day nitrofurantoin therapy is less effective than 7-day treatment in pregnant women, we recommend 7-day
treatment for ASB.
Microleakage of contemporary composite systems in dentin cavities
Authors: Stojanac Igor , Drobac Milan , Petrovic Ljubomir , Stojsin Ivana
Published: November 2009

This study evaluated microleakage in vitro of self-etch and multi-step, total-etch adhesive systems. Ninety extracted non-carious human molars were randomly assigned to nine groups (n=10) and restored with nine different composite systems: Gluma CPS/Charisma, Syntac Sprint/Tetric Ceram, 3M Single Bond/Silux, Admira Bond/Admira, Optibond Solo Plus/Herculite, Trendy Bond/Saremco, Excite/Tetric Ceram, Syntac Sprint/Compoglass and Promt-L-Pop/Silux. Cavities (2 mm diameter/2 mm deep) were prepared on the facial and lingual surfaces of each tooth previously abraded with a silicon-carbide abrasion discs to produce two level dentin surfaces with whole margins in dentin.Each group of composite systems was treated following the manufacturer's instructions. After they were finished and polished, the specimens were subjected to 100 thermal cycles in baths of 4 degrees+/-2 degrees C and 58 degrees+/-2 degrees C with 60 seconds of dwell time for each bath. After the thermocycling, the specimens were sealed with acid-resistant varnish, leaving a 1-mm window around the cervical margin interface, and immersed in 1% methylene blue buffered solution for 4 hours. Then the specimens were sectioned longitudinally in half and evaluated under stereomicroscopy at 30 times magnification, using inserted millimeter measurer. Each specimen was measured for dye penetration, thickness of composite filling and distance from the bottom of cavity to the pulp chamber. The data were analyzed using Kruskal-Wallis Analysis of Variance (ANOVA) and Pearson t- test. Syntac Sprint/Tetric Ceram, 3M Single Bond/Silux, Admira Bond/Admira, Optibond Solo Plus/Herculite and Gluma CPS/Charisma showed the least microleakage at the occlusal part of the cavity. There was no significant difference of microleakage at gingival part of cavity for all tested composite systems and the best sealing ability showed 3M Single Bond/Silux. Self-etch and multi-step, total-etch adhesive systems showed more or less similar microleakage 'in vitro' conditions and marginal sealing ability of all tested composite systems was significantly lower at gingival margins of cavities.
Characteristics of shigellosis outbreaks in the AP of Vojvodina
Authors: Djuric Predrag , Stefanovic Slavica , Petrovic Vladimir , Cosic Gorana
Published: November 2009

Introduction. Shigellosis causes around 165 million infections and around 1 million deaths in the world every year. Two thirds of both infections and deaths are among children younger than 10. Shigellosis mainly spreads by direct or indirect contact, but water- and food-borne outbreaks are not rare. Material and methods. A descriptive epidemiological method was used to analyse characteristics of shigellosis outbreaks in the AP of Vojvodina in the period 1979-2005. Results. During this period 9.083 shigellosis infections were registered, 51,9% of them in 202 shigellosis outbreaks. The leading way of transmission was contact, but water- and food-borne outbreaks were also detected. The average number of infections in contact outbreaks of shigellosis was small - 6.3 infections. The highest average is in water-borne outbreaks - 55.1. Most of the outbreaks were those occurring in families (47.5%) and most of them were registered in august. Discussion. Shigellosis has been mandatory reported in the AP of Vojvodina since 1945 and results of outbreak investigation of this disease were analyzed since 1979. In the first half of this period water was the most common way of agent transmission in shigellosis outbreaks, but in recent 15 years the contact became the leading one. In the last 5 years there was no water-borne shigellosis outbreaks. Almost one third of all outbreaks were imported from Montenegro and Croatia by tourists coming back from those countries. Most of the outbreaks are small outbreaks occurring in families, primarily transmitted by contact. Outbreaks in facilities for care of disabled children and elders are also important. Sh. sonnei and Sh. flexneri are the two serotypes identified, the former in 57.4% and the latter in 40.1% outbreaks. Conclusion. Shigellosis is a disease occurring in the AP of Vojvodina primarily in small outbreaks inside families, transmitted by contact, most often in August and more often caused by Sh. sonnei. Health promotion and strict use of general measures of disease control and prevention are important.
Relevance of Polymerase Chain Reaction technique in immunogenetics and histocompatibility
Authors: Vojvodic Svetlana
Published: November 2009

Introduction. During the last decade of the previous century, among many of developing sciences, molecular biology had the most important position. The greatest influence on the development of scientific knowledge had been brought by discovery of PCR technique, that showed numerous advantages in comparison to the existing techniques. PCR Procedure. The capability of PCR technique to amplify specific DNA sequences, in a simple, automatic procedure, accelerated the development of many fields in molecular biology researches such as cloning, identification of new genes and pathogenes, determination and quantification of nucleotide sequences, thus opening fields of experimental investigations and its clinical application. PCR technique is widely used in various investigations from anthropological researches to those in molecular biology, from basic genetic investigations to clinical diagnostics. Application of PCR procedure in the field of immunogenetics and histocompatibility In the field of immunogenetics and histocompatibility, there are several HLA genotyping techniques: PCR-SSOP, detection by sequence specific oligonucleotide probes, PCR-SSP, detection by sequence specific primers, RSCA, detection by Reference-Strand Conformation Analysis, SBT-Sequence Based Typing. the development of these techniques has enabled the testing of the HLA alleles as well as detection of shared nucleotide sequencies between alleles on the same or/and different loci and the existence of some locus-specific nucleotide sequences in coding (exon) and noncoding (intron) regions. Conclusion The application of PCR technique in immunogenetics made it possible to define genetic polymorphism in HLA system, which contributed to a significant progress in the field of tissue and organ transplantation, population and genetic studies as well as in studies of disease assotiation and HLA alleles.
Immunomodulatory actions of antibiotics
Authors: Minic Svetlana , Bojic Milena , Vukadinov Jovan , Canak Grozdana , Fabri Milotka , Bojic Ivanko
Published: November 2009

Introduction. Antimicrob drugs and immune system interaction has been studied since the pioneer works of Metchnikoff. After the introduction of antibiotics in clinical practice this area has attracted little attention of investigators, because of the lack of standards. This is the reason that the studying of the influence of antibiotics on immune system is still at its beginning. Aim: To point out the immunomodulatory action of some antibiotics on certain components of immune system. Methods and results. The literaure findings show that antibiotics exspress immunomodulatory action on some components of immune system such as fagocytes (polymorphonucleary, macrophages, monocytes), cytokines, immunoglobulines, and on cellular immunity. The principles of antibiotics action on phagocyte are the inhibition of chemotaxis and oxidants production. Macrolides applied for a short time enchance the phagocytic functions while their long use leads to immunosupression. Some cephalosporines and rifampicin in therapeutic doses inhibit the oxydative metabolism of macrophages. Tetracyclines, clindamycines, chloramphenicol and tobramycin inhibit the synthesis of superoxyd anione. The action of some antibiotics on cytokine and specific antibodies is also important. Cellular immunity can be affected as well. After administration of certain antibiotics it takes 1-2 weeks to reestablish normal cellular immunity, and for other even more. Conclusion. There is still no clear standing on real effects of antibiotics on the immune system. Clinicians should search for more information from this new-old field of investigation in order to give more adequate therapy to patients.
Kell immunization: A case report
Authors: Tasic Marija , Milosevic Jelena , Stefanovic Milan , Radovic-Janosevic Dragana , Krstic Miljan , Antic Vladimir
Published: November 2009

Introduction. The frequency of occurrence of RhD alloimmunization, due to preventive protocols, is decreased in our country, but more often there are other antigens that emerge as a cause of hemolytic disease of fetus. The most prominent is Kell antigen, which promotes specific course of disease based on an innate pathogenetic mechanism. Anti- Kell antibody production is, just as in other atypical antibodies, provoked with transfusion of incompatible blood. Except for the immune-mediated hemolysis, anti - Kell antibodies can also inhibit the function of progenitor (erytroid and megakariocyte) cell lines. Case report. We present the case of G1P1 woman in whom a distinct fetal hydrops was sonographically detected in the 28th week of pregnancy. The results of immunological tests undoubtedly pointed to Kell immunization (anti - Kell antibody titer was more than 1:32), and antenatal tests for evaluation of fetal condition (Doppler ultrasound and CTG) clearly showed the severe form of hemolytic disease. We concluded that the fetus was in a hopeless, terminal stage of the disease, and then decided to terminate the pregnancy. Conclusion. The only clinical approach to a problem of Kell alloimunization is active one. Early cordocentesis is recommended as the optimal method for evaluation of fetal condition. The clinical outcome of the fetus will strictly depend on a timely intrauterine transfusion (IUT) procedure. Prophylaxis emerges as a crucial factor in prevention of Kell - alloimmunization. It is to be considered that all females in childhood and throughout the reproductive period should take only K1 - negative blood transfusion in order to decrease the incidence of Kell - alloimmunization.
Computational study of the effect of different injection angle on heavy duty diesel engine combustion
Authors: Ranjbar Ali , Sedighi Kurosh , Farhadi Mousa , Pourfallah Mohsen
Published: November 2009

Diesel engines exhausting gaseous emission and particulate matter have long been regarded as one of the major air pollution sources, particularly in metropolitan areas, and have been a source of serious public concern for a long time. The choosing various injection strategies is not only motivated by cost reduction but is also one of the potentially effective techniques to reduce exhaust emission from diesel engines. The purpose of this study is to investigate the effect of different injection angles on a heavy duty diesel engine and emission characteristics. The varieties of injection angle were simulated and the emissions like soot and NO is calculated. The comparison between the different injection strategies was also investigated. A combustion chamber for three injection strategies (injection direction with angles of ?=67.5, 70, and 72.5 degree) was simulated. The comparative study involving rate of heat release, in-cylinder temperature, in-cylinder pressure, NO and soot emissions were also reported for different injection strategies. The case of ?=70 is optimum because in this manner the emissions are lower in almost most of crank angle than two other cases and the in-cylinder pressure, which is a representation of engine power, is higher than in the case of ?=67.5 and just a little lower than in the case of ?=72.5.
Numerical study of hydrogen mild combustion
Authors: Mollica Enrico , Giacomazzi Eugenio , di Marco
Published: November 2009

In this article a combustor burning hydrogen and air in mild regime is numerically studied by means of computational fluid dynamic simulations. All the numerical results show a good agreement with experimental data. It is seen that the flow configuration is characterized by strong exhaust gas recirculation with high air preheating temperature. As a consequence, the reaction zone is found to be characteristically broad and the temperature and concentrations fields are sufficiently homogeneous and uniform, leading to a strong abatement of nitric oxide emissions. It is also observed that the reduction of thermal gradients is achieved mainly through the extension of combustion in the whole volume of the combustion chamber, so that a flame front no longer exists ('flameless oxidation'). The effect of preheating, further dilution provided by inner recirculation and of radiation model for the present hydrogen/air mild burner are analyzed.
Artificial neural network modeling of jatropha oil fueled diesel engine for emission predictions
Authors: Ganapathy Thirunavukkarasu , Gakkhar Parkash , Murugesan Krishnan
Published: November 2009

This paper deals with artificial neural network modeling of diesel engine fueled with jatropha oil to predict the unburned hydrocarbons, smoke, and NOx emissions. The experimental data from the literature have been used as the data base for the proposed neural network model development. For training the networks, the injection timing, injector opening pressure, plunger diameter, and engine load are used as the input layer. The outputs are hydrocarbons, smoke, and NOx emissions. The feed forward back propagation learning algorithms with two hidden layers are used in the networks. For each output a different network is developed with required topology. The artificial neural network models for hydrocarbons, smoke, and NOx emissions gave R2 values of 0.9976, 0.9976, and 0.9984 and mean percent errors of smaller than 2.7603, 4.9524, and 3.1136, respectively, for training data sets, while the R2 values of 0.9904, 0.9904, and 0.9942, and mean percent errors of smaller than 6.5557, 6.1072, and 4.4682, respectively, for testing data sets. The best linear fit of regression to the artificial neural network models of hydrocarbons, smoke, and NOx emissions gave the correlation coefficient values of 0.98, 0.995, and 0.997, respectively.
Integrated gas dynamic and thermodynamic computational modeling of multicylinder 4-stroke spark ignition engine using gasoline as a fuel
Authors: Tirkey Jeevan , Gupta Hari , Shukla Shailendra
Published: November 2009

This paper presents a computational tool for the evaluation of engine performance and exhaust emissions for four stroke multi-cylinder spark ignition engine which uses gasoline as a fuel. Gas dynamics flow in multi-cylinder intake and exhaust systems are modeled by using one-dimensional unsteady compressible flow equations. The hyperbolic partial differential equations are transferred into a set of ordinary differential equations by using method of characteristics and solved by finite difference method. Compatibility relationships between local fluid velocity and sonic velocity are expressed in terms of Riemann variables, which are constant along the position characteristics. The equations are solved numerically by using rectangular grid in the flow direction and time. In this model nitric oxide concentration is predicted by using the rate kinetic model in the power cycle and along the exhaust pipes. Carbon monoxide is computed under chemical equilibrium condition and then empirical adjustment is made for kinetic behaviors based upon experimental results. A good agreement is obtained in the comparison of computed and experimental results of instantaneous cylinder pressure, manifold pressure and temperature, and nitric oxide and carbon monoxide emissions level.
Biodiesel: An eco-friendly alternate fuel for the future: A review
Authors: Singaram Lakshmanan
Published: November 2009

In today's society, researchers around the world are searching for ways to develop alternate forms of fuel. With the ever-rising fuel costs, developing alternate energy is a top priority. Biodiesel was developed to combat the high gas and oil prices. It is especially made for use in diesel cars and trucks. Biodiesel can be made from all natural foods that can produce oil. Oils such as vegetable, canola, peanut, rapeseed, palm, and olive oil can be used as bio diesel fuel. Virtually all oils that are used in the kitchens everyday can fuel automobiles. Biodiesel fuel is better for the environment because it burns cleaner and does not pollute the atmosphere. It is non-toxic and biodegradable, making it the perfect fuel. Many car manufacturers are realizing that the bio diesel automobile is becoming more popular, and are jumping on the bandwagon, by developing their own version of a biodiesel vehicle. They realize that the need for these vehicles will increase, and predict that they will be ready for the onslaught. Diesel engines have superior fuel efficiencies, and hence they are predominantly used in commercial transportation and agricultural machinery. Due to the shortage of diesel fuel and its increasing costs, a need for an alternate source of fuel for diesel engines is imminent. This paper investigates the suitability of biodiesels as such an alternative with particular reference to automobiles. It reviews techniques used to produce biodiesel and provides a comprehensive analysis of the benefits of using biodiesel over other fuels.
Developing an International Assurance Standard on Greenhouse Gas Statements
Authors: Simnett Roger , Nugent Michael , Huggins Anna L.
Published: November 2009

SYNOPSIS: Worldwide public concern over climate change and the need to limit greenhouse gas (hereafter, GHG) emissions has increasingly motivated public officials to consider more stringent environmental regulation and standards. The authors argue that the development of a new international assurance standard on GHG disclosures is an appropriate response by the auditing and assurance profession to meet these challenges. At its December 2007 meeting, the International Auditing and Assurance Standards Board (hereafter, IAASB) approved a project to consider the development of such a standard aimed at promoting trust and confidence in disclosures of GHG emissions, including disclosures required under emissions trading schemes. The authors assess the types of disclosures that can be assured, and outline the issues involved in developing an international assurance standard on GHG emissions disclosures. The discussion synthesizes the insights gained from four international roundtables on the proposed IAASB assurance standard held in Asia-Pacific, North America, and Europe during 2008, and an IAASB meeting addressing this topic in December 2008.
The Impact of Academic Accounting Research on Professional Practice: An Analysis by the AAA Research Impact Task Force
Authors:   AAA Research Impact Task Force
Published: November 2009

SYNOPSIS: The accounting academy has been long recognized as the premier developer of entry-level talent for the accounting profession and the major provider of executive education via master’s-level curricula and customized executive education courses. However, the impact that the academy’s collective ideas have had on the efficiency and effectiveness of practice has been less recognized. In this paper, we summarize key contributions of academic accounting research to practice in financial accounting, auditing, tax, regulation, managerial accounting, and information systems. Our goal is to increase awareness of the effects of academic accounting research. We believe that if this impact is more fully recognized, the practitioner community will be even more willing to invest in academe and help universities address the escalating costs of training and retaining doctoral-trained research faculty. Furthermore, we believe that this knowledge will attract talented scholars into the profession. To this end, we encourage our colleagues to refer liberally to research successes such as those cited in this paper in their classes, in their textbooks, and in their presentations to nonacademic audiences.
Ventromedial Hypothalamic Nitric Oxide Production Is Necessary for Hypoglycemia Detection and Counterregulation
Authors: Fioramonti Xavier , Marsollier Nicolas , Song Zhentao , Fakira Kurt A. , Patel Reema M. , Brown Stacey , Duparc Thibaut , Pica-Mendez Arnaldo , Sanders Nicole M. , Knauf Claude , Valet Philippe , McCrimmon Rory J. , Beuve Annie , Magnan Christophe , Routh Vanessa H.
Published: November 2009

OBJECTIVE

The response of ventromedial hypothalamic (VMH) glucose-inhibited neurons to decreased glucose is impaired under conditions where the counterregulatory response (CRR) to hypoglycemia is impaired (e.g., recurrent hypoglycemia). This suggests a role for glucose-inhibited neurons in the CRR. We recently showed that decreased glucose increases nitric oxide (NO) production in cultured VMH glucose-inhibited neurons. These in vitro data led us to hypothesize that NO release from VMH glucose-inhibited neurons is critical for the CRR.

RESEARCH DESIGN AND METHODS

The CRR was evaluated in rats and mice in response to acute insulin-induced hypoglycemia and hypoglycemic clamps after modulation of brain NO signaling. The glucose sensitivity of ventromedial nucleus glucose-inhibited neurons was also assessed.

RESULTS

Hypoglycemia increased hypothalamic constitutive NO synthase (NOS) activity and neuronal NOS (nNOS) but not endothelial NOS (eNOS) phosphorylation in rats. Intracerebroventricular and VMH injection of the nonselective NOS inhibitor NG-monomethyl-l-arginine (l-NMMA) slowed the recovery to euglycemia after hypoglycemia. VMH l-NMMA injection also increased the glucose infusion rate (GIR) and decreased epinephrine secretion during hyperinsulinemic/hypoglycemic clamp in rats. The GIR required to maintain the hypoglycemic plateau was higher in nNOS knockout than wild-type or eNOS knockout mice. Finally, VMH glucose-inhibited neurons were virtually absent in nNOS knockout mice.

CONCLUSIONS

We conclude that VMH NO production is necessary for glucose sensing in glucose-inhibited neurons and full generation of the CRR to hypoglycemia. These data suggest that potentiating NO signaling may improve the defective CRR resulting from recurrent hypoglycemia in patients using intensive insulin therapy.
Regulation of MAP Kinase–Directed Mitogenic and Protein Kinase B–Mediated Signaling by Cannabinoid Receptor Type 1 in Skeletal Muscle Cells
Authors: Lipina Christopher , Stretton Clare , Hastings Simon , Hundal Jonathan S. , Mackie Ken , Irving Andrew J. , Hundal Harinder S.
Published: November 2009

OBJECTIVE

The endogenous cannabinoid (or endocannabinoid) system (ECS) is part of a central neuromodulatory system thought to play a key role in the regulation of feeding behavior and energy balance. However, increasing evidence suggests that modulation of the ECS may also act to regulate peripheral mechanisms involved in these processes, including lipogenesis in adipose tissue and liver, insulin release from pancreatic β-cells, and glucose uptake into skeletal muscle. It was recently shown that cannabinoid receptor type 1 (CB1) and type 2 (CB2), both key components of the ECS, are expressed in human and rodent skeletal muscle. However, their role in modulating insulin sensitivity in this metabolically active tissue has yet to be determined. Our aim was to establish the role, if any, of these receptors in modulating insulin sensitivity in skeletal muscle cells.

RESEARCH DESIGN AND METHODS

Cultured skeletal muscle cells were exposed to CB1 and/or CB2 pharmacological agonists/antagonists/inverse agonists, and the resulting effects on insulin-regulated phosphatidylinositol 3 kinase (PI 3-kinase)–protein kinase B (PKB) and extracellular signal–related kinases 1/2 (ERK1/2)-directed signaling were determined.

RESULTS

Here, we report that modulating the activity of the ECS in skeletal muscle regulates both insulin-dependent mitogen-activated protein (MAP) kinase (ERK1/2) and the canonical PI 3-kinase/PKB signaling pathways. We show that pharmacological activation or inhibition of CB1 receptor activity exerts a differential effect with regard to MAP kinase– and PKB-directed signaling.

CONCLUSIONS

Our study provides evidence that signaling via cannabinoid receptors can significantly modulate mitogenic and metabolic signaling in skeletal muscle with important implications for muscle growth and differentiation as well as the regulation of glucose and lipid metabolism.
Human Recombinant ACE2 Reduces the Progression of Diabetic Nephropathy
Authors: Oudit Gavin Y. , Liu George C. , Zhong JiuChang , Basu Ratnadeep , Chow Fung L. , Zhou Joyce , Loibner Hans , Janzek Evelyne , Schuster Manfred , Penninger Josef M. , Herzenberg Andrew M. , Kassiri Zamaneh , Scholey James W.
Published: November 2009

OBJECTIVE

Diabetic nephropathy is one of the most common causes of end-stage renal failure. Inhibition of ACE2 function accelerates diabetic kidney injury, whereas renal ACE2 is downregulated in diabetic nephropathy. We examined the ability of human recombinant ACE2 (hrACE2) to slow the progression of diabetic kidney injury.

RESEARCH DESIGN AND METHODS

Male 12-week-old diabetic Akita mice (Ins2WT/C96Y) and control C57BL/6J mice (Ins2WT/WT) were injected daily with placebo or with rhACE2 (2 mg/kg, i.p.) for 4 weeks. Albumin excretion, gene expression, histomorphometry, NADPH oxidase activity, and peptide levels were examined. The effect of hrACE2 on high glucose and angiotensin II (ANG II)–induced changes was also examined in cultured mesangial cells.

RESULTS

Treatment with hrACE2 increased plasma ACE2 activity, normalized blood pressure, and reduced the urinary albumin excretion in Akita Ins2WT/C96Y mice in association with a decreased glomerular mesangial matrix expansion and normalization of increased α-smooth muscle actin and collagen III expression. Human recombinant ACE2 increased ANG 1–7 levels, lowered ANG II levels, and reduced NADPH oxidase activity. mRNA levels for p47phox and NOX2 and protein levels for protein kinase Cα (PKCα) and PKCβ1 were also normalized by treatment with hrACE2. In vitro, hrACE2 attenuated both high glucose and ANG II–induced oxidative stress and NADPH oxidase activity.

CONCLUSIONS

Treatment with hrACE2 attenuates diabetic kidney injury in the Akita mouse in association with a reduction in blood pressure and a decrease in NADPH oxidase activity. In vitro studies show that the protective effect of hrACE2 is due to reduction in ANG II and an increase in ANG 1–7 signaling.
Divergent Regulation of Energy Expenditure and Hepatic Glucose Production by Insulin Receptor in Agouti-Related Protein and POMC Neurons
Authors: Lin Hua V. , Plum Leona , Ono Hiraku , Gutiérrez-Juárez Roger , Shanabrough Marya , Borok Erzsebet , Horvath Tamas L. , Rossetti Luciano , Accili Domenico
Published: November 2009

OBJECTIVE

The sites of insulin action in the central nervous system that regulate glucose metabolism and energy expenditure are incompletely characterized. We have shown that mice with hypothalamic deficiency (L1) of insulin receptors (InsRs) fail to regulate hepatic glucose production (HGP) in response to insulin.

RESEARCH DESIGN AND METHODS

To distinguish neurons that mediate insulin's effects on HGP from those that regulate energy homeostasis, we used targeted knock-ins to express InsRs in agouti-related protein (AgRP) or proopiomelanocortin (POMC) neurons of L1 mice.

RESULTS

Restoration of insulin action in AgRP neurons normalized insulin suppression of HGP. Surprisingly, POMC-specific InsR knock-in increased energy expenditure and locomotor activity, exacerbated insulin resistance and increased HGP, associated with decreased expression of the ATP-sensitive K+ channel (KATP channel) sulfonylurea receptor 1 subunit, and decreased inhibitory synaptic contacts on POMC neurons.

CONCLUSIONS

The contrasting phenotypes of InsR knock-ins in POMC and AgRP neurons suggest a branched-pathway model of hypothalamic insulin signaling in which InsR signaling in AgRP neurons decreases HGP, whereas InsR activation in POMC neurons promotes HGP and activates the melanocortinergic energy expenditure program.
Depression and Advanced Complications of Diabetes
Authors: Lin Elizabeth H.B. , Rutter Carolyn M. , Katon Wayne , Heckbert Susan R. , Ciechanowski Paul , Oliver Malia M. , Ludman Evette J. , Young Bessie A. , Williams Lisa H. , McCulloch David K. , Von Korff Michael
Published: November 2009

OBJECTIVE

To prospectively examine the association of depression with risks for advanced macrovascular and microvascular complications among patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

A longitudinal cohort of 4,623 primary care patients with type 2 diabetes was enrolled in 2000–2002 and followed through 2005–2007. Advanced microvascular complications included blindness, end-stage renal disease, amputations, and renal failure deaths. Advanced macrovascular complications included myocardial infarction, stroke, cardiovascular procedures, and deaths. Medical record review, ICD-9 diagnostic and procedural codes, and death certificate data were used to ascertain outcomes in the 5-year follow-up. Proportional hazard models analyzed the association between baseline depression and risks of adverse outcomes.

RESULTS

After adjustment for prior complications and demographic, clinical, and diabetes self-care variables, major depression was associated with significantly higher risks of adverse microvascular outcomes (hazard ratio 1.36 [95% CI 1.05–1.75]) and adverse macrovascular outcomes (1.24 [1.0–1.54]).

CONCLUSIONS

Among people with type 2 diabetes, major depression is associated with an increased risk of clinically significant microvascular and macrovascular complications over the ensuing 5 years, even after adjusting for diabetes severity and self-care activities. Clinical and public health significance of these findings rises as the incidence of type 2 diabetes soars. Further research is needed to clarify the underlying mechanisms for this association and to test interventions to reduce the risk of diabetes complications among patients with comorbid depression.
Declining β-Cell Compensation for Insulin Resistance in Hispanic Women With Recent Gestational Diabetes Mellitus
Authors: Xiang Anny H. , Kawakubo Miwa , Trigo Enrique , Kjos Siri L. , Buchanan Thomas A.
Published: November 2009

OBJECTIVE

To identify factors associated with declining β-cell compensation for insulin resistance.

RESEARCH DESIGN AND METHODS

In a cohort of Hispanic women with recent gestational diabetes mellitus, oral glucose tolerance tests (OGTTs), intravenous glucose tolerance tests (IVGTTs), and bioelectrical impedance measurements were performed at 15-month intervals for up to 5 years, or until fasting plasma glucose exceeded 140 mg/dl (7.8 mmol/l). Data were analyzed to identify predictors of declining β-cell compensation for insulin resistance (the disposition index [DI]) and to examine the mechanism of weight gain and changes in circulating levels of selected adipokines and inflammatory markers on β-cell compensation decline.

RESULTS

A total of 60 nondiabetic women had a median of four sets of OGTT + IVGTT during a median follow-up of 52 months. Fourteen of the women developed diabetes. None of the baseline characteristics were significantly predictive of a decline in DI. There were significant univariate associations between declining DI and weight gain (specifically fat gain), declining adiponectin and rising C-reactive protein. Multivariate analysis showed that the weight gain was the most significant factor associated with declining DI. The amount of association between weight gain and declining DI was explained 31% by changes in adiponectin and C-reactive protein and 40% by changes in insulin resistance.

CONCLUSIONS

These results identify weight gain as the strongest factor associated with declining β-cell compensation for insulin resistance in Hispanic women at high risk for type 2 diabetes. Such effect may be mediated through at least two effects: alterations in adipokine levels and increasing insulin resistance.
Effects of Metformin With or Without Supplementation With Folate on Homocysteine Levels and Vascular Endothelium of Women With Polycystic Ovary Syndrome
Authors: Palomba Stefano , Falbo Angela , Giallauria Francesco , Russo Tiziana , Tolino Achille , Zullo Fulvio , Colao Annamaria , Orio Francesco
Published: November 2009

OBJECTIVE

To evaluate whether the administration of metformin exerts any effects on serum homocysteine (Hcy) levels in patients with polycystic ovary syndrome (PCOS) and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium.

RESEARCH DESIGN AND METHODS

A total of 50 patients affected by PCOS, without additional metabolic or cardiovascular diseases, were enrolled in a prospective nonrandomized placebo-controlled double-blind clinical study. They were grouped into two treatment arms that were matched for age and BMI. Patients were treated with a 6-month course of metformin (1,700 mg daily) plus folic acid (400 μg daily; experimental group, n = 25) or placebo (control group, n = 25). Complete hormonal and metabolic patterns, serum Hcy, folate, vitamin B12, endothelin-1 levels, brachial artery diameter at the baseline (BAD-B) and after reactive hyperemia (BAD-RH), flow-mediated dilation, and intima-media thickness in both common carotid arteries were evaluated.

RESULTS

After treatment, a significant increase in serum Hcy levels was observed in the control group compared with the baseline values and the experimental group. A beneficial effect was observed in the concentrations of BAD-B, BAD-RH, flow-mediated dilation, intima-media thickness, and serum endothelin-1 in both groups. However, the results were improved more significantly in the experimental group than in the control subjects.

CONCLUSIONS

Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS, and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium.
Quantitative Loci Regulating Plasma Levels of γ Glutamyl Transferase and Albumin and Their Genetic Correlations with Cardiovascular Risk Factors
Authors: Bose Tanushree , Voruganti V. Saroja , Tejero M. Elizabeth , Proffitt J. Michael , Cox Laura A. , VandeBerg John L. , Mahaney Michael C. , Rogers Jeffrey , Freeland-Graves Jeanne H. , Cole Shelley A. , Comuzzie Anthony G.
Published: November 2009

γ Glutamyl transferase (GGT) and albumin (ALB) are two markers of liver function. These two proteins have been associated with non-alcoholic fatty liver disease and cardiovascular disease. The objectives of this study were to explore the genetic factors that influence variation in the plasma levels of GGT and ALB and to evaluate their genetic correlations with cardiovascular risk factors. Baboons from the Southwest National Primate Research Center at the Southwest Foundation for Biomedical Research, San Antonio, TX, were used as an animal model. The baboons were fed a standard monkey chow diet ad libitum. Fasting plasma concentrations of GGT, ALB, triglycerides, total cholesterol and LDL cholesterol were measured in 350 pedigreed adult baboons by standard assay procedures. A maximum likelihood-based variance decomposition approach implemented in the computer program SOLAR was used to conduct genetic analyses. The heritabilities of GGT (h2 = 0.55; P < 0.0001) and ALB (h2 = 0.42; P < 0.01) were significant. No statistically significant associations were found between GGT and the cardiovascular-related phenotypes. Genetic correlations between ALB and total cholesterol, LDL cholesterol and triglycerides were significant. A QTL (LOD = 2.8) for GGT plasma levels was identified on the baboon homologue of human chromosome 22 between markers D22S304 and D22S280. A QTL (LOD = 2.3) near marker D10S1432 was detected on the baboon homologue of human chromosome 10 for ALB. These results imply that variations in the plasma levels of GGT and ALB are under significant genetic regulation and that a common genetic component influences ALB and cardiovascular risk factor phenotypes.
Cardiovascular Applications of Hyperpolarized Contrast Media and Metabolic Tracers
Authors: Bhattacharya Pratip , Ross Brian D. , Bünger Rolf
Published: November 2009

Modern hyperpolarization technology enhances the recordable magnetic resonance signal four to five orders of magnitude, making in vivo assessments of tracer pathways and metabolic compartments feasible. Existing hyperpolarization instrumentation and previous tracer studies using hydroxyethylpropionate (HEP) as an extracellular marker and 14-carbon label pyruvate as examples are described and reviewed as applicable to the working heart. Future metabolic imaging based on the use of hyperpolarized pyruvate needs to consider extra- and intra-cellular label dilution due to glycolysis, lactate oxidation and protein degradation. This dilution can substantially decrease the recordable signals from PDH flux (oxidative decarboxylation of pyruvate) and other pyruvate pathways. The review of previous literature and data suggests that the 13C-alanine signal is a better index of mitochondrially oxidized pyruvate than L-lactate. These facts and considerations will help in the interpretation of the in vivo recorded hyperpolarization signals of metabolic tracers and contrast media.