bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Chorionic Gonadotropin (hCG) Up-Regulates wnt5b and wnt7b in the Mammary Gland, and hCGβ Transgenic Female Mice Present with Mammary Gland Tumors Exhibiting Characteristics of the Wnt/β-Catenin Pathway Activation
Authors: Kuorelahti Aino , Rulli Susana , Huhtaniemi Ilpo , Poutanen Matti
Published: May 2007

Transgenic (TG) mice expressing human chorionic gonadotropin (hCG) β-subunit under the ubiquitin C promoter, presenting with a moderately elevated level of LH/hCG bioactivity develop multiple neoplasms secondary to the endocrine abnormalities, including mammary gland tumors after the age of 9 months. The increased levels of circulating estradiol, progesterone, and prolactin of the TG females after puberty boost the lobuloalveolar development in the mammary gland resulting ultimately in the formation of estrogen and progesterone receptor-negative, malignant tumors. These tumors have a similar histopathology with those observed in TG mice with activated wnt/β-catenin pathway, showing increased expression of β-catenin, also a common finding in human breast tumors. Transdifferentiation is observed in mammary tumors of the hCGβ TG mice, accompanied by abnormal expression of the Wnt genes in the tumorous and nontumorous mammary gland tissue. Specifically we found increased expression of Wnt5b in the TG mammary glands at the age of 3 months and up-regulation of Wnt7b and -5b in the subsequently appearing tumors. Importantly, hCG was found to up-regulate these wnt ligands in mouse mammary gland, independent of the changes in ovarian steroidogenesis. Thus, the hCGβ-overexpressing TG mice represent a novel model that links enhanced hCG action to dysregulated wnt signaling in the mammary gland, resulting in β-catenin-stabilizing mammary tumorigenesis. The novel finding of hCG up-regulating wnt7b and wnt5b could contribute to pregnancy-induced breast cancer in humans.
The Postimplantation Embryo Differentially Regulates Endometrial Gene Expression and Decidualization
Authors: Kashiwagi Aki , DiGirolamo Carla M. , Kanda Yoshiaki , Niikura Yuichi , Esmon Charles T. , Hansen Thomas R. , Shioda Toshi , Pru James K.
Published: May 2007

Transcriptomal changes in the uterine endometrium induced in response to the implanting embryo remain largely unknown. In this study, using Affymetrix mRNA expression microarray analysis, we identified genes differentially expressed in the murine endometrium in the presence or absence of the embryo. Compared with the pseudopregnant deciduoma induced by a mechanical stimulus in the absence of an embryo, approximately 1500 genes (753 up-regulated, 686 down-regulated; P < 0.05) were differentially expressed by at least 1.2-fold in the uterine decidua of pregnancy. Most of these genes fall into five major biological categories that include binding (45%), catalysis (24%), signal transduction (10%), transcriptional regulators (5%), and transporters (5%). This strong, embryo-induced transcriptomal impact represented approximately 10% of the total number of genes expressed in the decidualizing endometrium. Validation studies with mRNA and protein confirmed existence of the phylogenetically conserved, embryo-regulated genes involved in the following: 1) hemostasis and inflammation; 2) interferon signaling; 3) tissue growth and remodeling; and 4) natural killer cell function. Interestingly, whereas expression of many growth factors and their cognate receptors were not different between the decidual and deciduomal endometria, a number of proteases that degrade growth factors were selectively up-regulated in the decidual tissue. Increased expression of IGF and activin A neutralizing factors (i.e. HtrA1 and Fstl3) correlated with reduced stromal cell mitosis, tissue growth, and mitogenic signaling in the decidual endometrium. These results support the hypothesis that the implanting murine embryo takes a proactive role in modulating endometrial gene expression and development during early gestation.
Recent developments in exact strip analysis and optimum design of aerospace structures
Authors: Kennedy D , Fischer M , Featherston C A
Published: May 2007

The current paper outlines recent developments to algorithms and software for critical buckling and natural vibration analysis and optimum design of prismatic plate assemblies, based on the exact strip approach and the Wittrick—Williams algorithm. The current paper acts as a single source document discussing recent progress and planned future explorations in: initial local postbuckling of stiffened panels; discrete optimization of composite structures to satisfy manufacturing requirements; discontinuous cost functions; constraints on fundamental natural frequencies and frequency-free bands; a feasibility study of response surface optimization; and multi-level optimization of composite aircraft wings. The numerous references provide fuller technical details and illustrative examples.
Optimal stabilization and path-following controls for a bicycle
Authors: Sharp R S
Published: May 2007

The article is about stabilizing and path-tracking control of a bicycle by a rider. It is based on previously published work, in which it has been shown how a driver's or rider's preview of the roadway can be combined with the linear dynamics of an appropriate vehicle to yield a problem of discrete-time optimal-linear-control-theory form. In the previous work, it was shown how an optimal ‘driver’ converts path preview sample values, modelled as deriving from a Gaussian white-noise process, into steering control inputs to cause the vehicle to follow the previewed path. The control compromises between precision and ease, to an extent that is controllable through choice of weights in the optimal control calculations.

Research into the dynamics of bicycles has yielded a benchmark model, with equations of motion firmly established by extensive cross-checking. Model predictions have been verified for modest speeds by experimental testing. The established optimal linear preview stabilizing and tracking control theory is now brought together with the benchmark bicycle description to yield optimal controls for the bicycle for variations in speed and performance objectives. The resulting controls are installed in the bicycle, giving a virtual rider-controlled system, and frequency responses of the rider-controlled system are calculated to demonstrate tracking capability. Then path-tracking simulations are used to illustrate the behaviour of the controlled system. Tight and loose controls, representing different balances between tracking accuracy and control effort, are calculated and illustrated through the simulations.
Optimization of High-Resolution Melting Analysis for Low-Cost and Rapid Screening of Allelic Variants of Bacillus anthracis by Multiple-Locus Variable-Number Tandem Repeat Analysis
Authors: Fortini Daniela , Ciammaruconi Andrea , De Santis Riccardo , Fasanella Antonio , Battisti Antonio , D’Amelio Raffaele , Lista Florigio , Cassone Antonio , Carattoli Alessandra
Published: May 2007

Background: Molecular genotyping of Bacillus anthracis, the etiologic agent of anthrax, is important for differentiating and identifying strains from different geographic areas and for tracing strains deliberately released in a bioterrorism attack. We previously described a multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) based on 25 marker loci. Although the method has great differentiating power and reproducibility, faster genotyping at low cost may be requested to accurately identify B. anthracis strains in the field.

Methods: We used the High Resolution Melter-1 (Idaho Technology) and a saturating dye of double-stranded DNA (LCGreen I) to identify alleles via PCR and melting-curve analysis of the amplicons. We applied high-resolution melting analysis (HRMA) to a collection of 19 B. anthracis strains.

Results: HRMA produced reproducible results for 6 of the 25 B. anthracis loci tested. These easily interpretable and distinguishable melting curve results were consistent with MLVA results obtained for the same alleles. The feasibility of this method was demonstrated in testing of different allelic variants for the 6 selected loci.

Conclusions: The described HRMA application for screening B. anthracis VNTR loci is fast and widely accessible and may prove particularly useful under field conditions.
Increased Serum Lipoprotein(a) Concentrations and Low Molecular Weight Phenotypes of Apolipoprotein(a) Are Associated with Symptomatic Peripheral Arterial Disease
Authors: Dieplinger Benjamin , Lingenhel Arno , Baumgartner Nadja , Poelz Werner , Dieplinger Hans , Haltmayer Meinhard , Kronenberg Florian , Mueller Thomas
Published: May 2007

Background: Increased concentrations of lipoprotein(a) [Lp(a)] have been considered a genetically determined risk factor for coronary artery and cerebrovascular disease. Only 2 small and conflicting studies have investigated the possibility of an association of peripheral arterial disease (PAD) with high serum Lp(a) concentrations and low molecular weight (LMW) phenotypes of apolipoprotein(a) [apo(a)].

Methods: We measured serum concentrations of Lp(a) and apo(a) phenotypes in 213 patients with symptomatic PAD and 213 controls matched for sex, age (within 2 years), and presence of diabetes.

Results: Patients with PAD showed significantly higher median serum concentrations of Lp(a) (76 vs 47 mg/L; P = 0.003) and a higher frequency of LMW apo(a) phenotypes (41% vs 26%; P = 0.002) than controls. After adjustment for several potential confounders, increased Lp(a) concentrations (>195 mg/L, i.e., 75th percentile of the entire study sample) and LMW apo(a) phenotypes were significant predictors of PAD, with odds ratios of 3.73 (95% CI 2.08–6.67; P <0.001) and 2.21 (95% CI 1.33–3.67; P = 0.002), respectively.

Conclusions: In this study sample, both increased serum concentrations of Lp(a) and the presence of LMW apo(a) phenotypes were associated with the presence of symptomatic PAD independent of traditional and nontraditional cardiovascular risk factors. Because PAD is considered an indicator of systemic atherosclerotic disease, our results suggest a possible role of Lp(a) as a genetically determined marker for systemic atherosclerosis.
Concise Review: Dendritic Cell Development in the Context of the Spleen Microenvironment
Authors: Tan Jonathan K. H. , O'Neill Helen C.
Published: May 2007

The dendritic cell (DC) population in spleen comprises a mixture of cells including endogenous DC progenitors, DC precursors migrating in from blood and bone marrow, and DC in different states of differentiation and activation. A role for different microenvironments in supporting the dynamic development of murine DC of different types or lineages is considered here. Recent evidence for production of DC dependent on splenic stromal cells is reviewed in the light of evidence that cell production is dependent on cells comprising an endothelial niche in spleen. The possibility that self-renewing progenitors in spleen give rise to DC with tolerogenic or regulatory rather than immunostimulatory function is considered.

Disclosure of potential conflicts of interest is found at the end of this article.
The short- and long-term compressive behavior of high-density polyethylene geonet and geocomposite under inclined conditions
Authors: Yeo S.-S. , Hsuan Y. G.
Published: May 2007

The short- and long-term compressive behaviors of a high-density polyethylene (HDPE) geonet at five inclined conditions—horizontal (0°), 1(V)-to-9(H) (6.3°), 1-to-5 (11.3°), 1-to-4 (14.0°), and 1-to-3 (18.4°)—were evaluated. The results of the short-term tests indicate that the compressive strength decreases linearly with inclined angle, whereas the compressive strain increases. The long-term compressive behavior (i.e. creep) was evaluated using the stepped isothermal method (SIM) at applied stresses of 10%, 20% and 30% of the normal compressive strength. The creep strain increases with inclined angle at all applied stresses. At 10% applied stress the primary creep deformation is obtained, while the secondary and tertiary creep stages are detected at the two higher stresses. The relationship between compressive behavior and the rollover of upper ribs of the geonet is established. The geometry of the geonet, particularly the inclined angle of the ribs, is found to be critical to the short- and long-term behavior of the geonet. In addition, the short- and long-term compressive behavior of the geocomposite was evaluated at horizontal (0°) and 1-to-4 (14.0°) to investigate the effects of thermally bonded geotextiles. The results are different from those of the geonet alone owing to the localized interface friction between the needle-punched nonwoven geotextile and ribs.
Physical Modeling of LNAPL Source Zone Remediation by Air Sparging
Authors: Waduge W. A. P. , Soga K. , Kawabata J.
Published: May 2007

The mass removal behavior of pooled light nonaqueous phase liquid (LNAPL) by air sparging was investigated using one‐dimensional and two‐dimensional physical model experiments. The effects of flow rate, flow interruption, nonaqueous phase liquid (NAPL) saturation, and soil heterogeneity were examined. At the beginning of air sparging, a higher initial mass removal rate was achieved under near‐equilibrium condition but was limited to the volatilization of NAPL that is in direct contact with air channels. At the later stage of air injection, the mass partitioning from NAPL phase to gaseous phase became rate limited. In terms of final amount of mass removed, there was a negligible effect of air injection flow rate within the range examined. Results from two‐dimensional soil tank experiments revealed that fractional mass removal was extremely sensitive to subsurface heterogeneity. About 90% fractional mass removal was achieved in a case where NAPL was trapped in a coarse sand lens surrounded by a finer soil matrix. However, when NAPL was trapped in a fine sand lens in coarser sand matrix, the injected air channels diverted away from the entrapped NAPL due to the presence of the low‐permeability sand lens, and the fractional mass removal decreased to less than 50%. Flow interruption can be used to enhance the mass removal of LNAPLs entrapped around the water table by air sparging and soil vapor extraction. However, the fractional mass removal rate became zero at a threshold NAPL saturation beyond which NAPL could not be removed by air sparging even after many interruption cycles. Results indicate the necessity of incorporating a rate‐limited mass transfer model into the NAPL‐gas mass transfer model. The mass transfer rate should be a function of NAPL saturation and the threshold value determined by experiments.
Monitoring Surface and Subsurface Water Storage Using Confined Aquifer Water Levels at the Savannah River Site, USA
Authors: Rasmussen Todd C. , Mote Thomas L.
Published: May 2007

Surface and subsurface water storage is an important component of hydrologic models, needed to account for groundwater recharge, lateral water movement, and evapotranspiration. Yet methods for estimating above‐ and belowground water storage include substantial uncertainties. This paper demonstrates that water levels in the Gordon aquifer (a confined aquifer at the USDOE Savannah River Site, near Aiken, SC) fluctuate in response to changes in total water storage. An increase in surface loading is known to cause a measurable increase in aquifer fluid pressure whenever the aquifer skeletal compressibility is sufficiently large. Water levels in the Gordon aquifer respond rapidly during precipitation events, which is consistent with increased loading that compresses the aquifer at depth. Instantaneous barometric and loading efficiencies of approximately 6 and 91%, respectively, are consistent with a poorly consolidated aquifer. Because the aquifer has a high loading efficiency, it behaves like a geological weighing lysimeter that appears to estimate water storage. Following precipitation events, aquifer water levels decline over time, presumably due to unloading by evapotranspiration plus net lateral water export. The water‐storage signal is improved by incorporating (i) the lagged response between aquifer load and borehole water‐level changes and (ii) the removal of periodic Earth tides.
Root Functional Architecture: A Framework for Modeling the Interplay between Roots and Soil
Authors: Pierret Alain , Doussan Claude , Capowiez Yvan , Bastardie François , Pagès Loïc
Published: May 2007

Soil ecosystems support a plethora of intertwined biophysical and biochemical processes. Soil structure plays a central role in the formation and maintenance of soil biological activity by providing a diversified habitat for soil organisms and determining the movement and transport of the resources on which they rely. At the same time, the formation and preservation of soil structure and fertility is also strongly linked to soil biological activity through feedback loops. In most soil ecosystems, soil biological activity and associated processes are concentrated in the soil located around living plant roots and influenced by root activity, an environment known as the rhizosphere. Consequently, among the wide array of soil life forms, plants play a dominant role in the regulation of many soil processes. In this paper, we illustrate the functional complexity of soil ecosystems using specific examples of root–soil interactions and associated processes. Through examples taken from the literature, we examine the origins and variations in soil physical, chemical, and biological properties and their impact on root growth. Next, we consider how the response of root systems to their environment affects resource acquisition by plants. Finally, we describe how the concept of root functional architecture can improve the integration of research advances from fields operating as independent disciplines and improve our understanding of soil ecosystems.
Environmental Availability of Uranium in an Acidic Plume at the Savannah River Site
Authors: Serkiz S. M. , Johnson W. H. , Wile L. M. Johnson , Clark S. B.
Published: May 2007

Uranium partitioning in soils collected from an acid and U impacted sandy Coastal Plain aquifer at the Savannah River Site (SRS) was investigated. The influences of hydrologic regime (vadose zone or saturated zone), proximity to the source input (impacted or unimpacted soils), and soil weathering (field or laboratory‐spiked soils) on the environmental availability U were examined. Environmental availability (availability for groundwater transport) was operationally defined using a sequential extraction technique and was applied to vadose zone, saturated zone, and background soils. For saturated zone locations, matched porewater–soil sets of field samples were collected, and data generated from these samples were used to examine U partitioning under field conditions. Laboratory batch sorption studies of uranyl ion to background soils were conducted as a function of pH. Subsequently, the soil used in the sorption study was subjected to sequential extraction to investigate the environmental availability in laboratory spiked samples. Based on sequential extraction behavior of U‐impacted soils and background soils and the acidic plume chemistry, U concentrations in the first three sequential extraction steps [deionized water, CaCl2, and acetic acid/Ca(NO3)2] were operationally defined as available, and the final two extraction steps (crystalline iron oxide and residual extraction steps) were operationally defined as unavailable. Based on this operational definition, soils impacted by the acidic U plume exhibited a greater fraction of available and total U. Vadose‐zone soils had a smaller fraction of available U than corresponding saturated zone samples. Sequential extractions of U sorbed to background soils in a short‐term laboratory experiment showed greater U availability compared with field soils collected within the contaminant plume. Field‐derivedKdvalues ranged from 0.1 to 300 L kg−1and were highly correlated with porewater pH.
Extracellular Polymeric Substances Affecting Pore‐Scale Hydrologic Conditions for Bacterial Activity in Unsaturated Soils
Authors: Or Dani , Phutane Sachin , Dechesne Arnaud
Published: May 2007

Soil bacterial cells are often found embedded in biosynthesized extracellular polymeric substances (EPS) forming aggregates or stationary colonies attached to solid surfaces. Soil bacterial aggregation and pooling of resources offer a successful adaptation to variations in hydration status and in nutrient availability and enhance cooperative genetic and metabolic exchanges. The ubiquity of such microbially excreted exopolymeric substances across many different environmental conditions and habitats is attributed to their key role in environmental adaptation, including colony architecture and anchoring, nutrient entrapment, and maintenance of favorable hydration conditions. This review focuses on the hydrophysical properties of EPS and its primary constituent, exopolysaccharides, and their role as an interface between living cells and the harsh conditions common to the shallow vadose zone. We review water retention, diffusion, and hydraulic properties of EPS and postulate mechanisms conferring an advantage to embedded bacterial cells. The shrink–swell behavior of EPS for different water potentials affects mean pore size and passage of solutes and colloids of different sizes; we evaluate various water‐related morphological transformations of EPS that influence diffusion behavior in unsaturated soils. We hypothesize that EPS low permeability results in hydraulic decoupling during rapid wetting or drying events, effectively shielding embedded bacterial cells from adverse effects of extreme fluctuations in hydration conditions. We show that the addition of minute amounts of EPS significantly alters the hydrological conditions experienced by microbial colonies and, in some case, may alter macroscopic hydrological and mechanical properties of the host porous medium.
Application of Computational Fluid Dynamics to Closed‐Loop Bioreactors: II. Simulation of Biological Phosphorus Removal Using Computational Fluid Dynamics
Authors: Littleton Helen X. , Daigger Glen T. , Strom Peter F.
Published: May 2007

Based on the International Water Association's (London) Activated Sludge Model No. 2 (ASM2), biochemistry rate expressions for general heterotrophs and phosphorus‐accumulating organisms (PAOs) were introduced to a previously developed, three‐dimensional computational fluid dynamics (CFD) activated sludge model that characterized the mixing pattern within the outer channel of a full‐scale, closed‐loop bioreactor. Using acetate as the sole carbon and energy source, CFD simulations for general heterotrophs or PAOs individually agreed well with those of ASM2 for a chemostat with the same operating conditions. Competition between and selection of heterotrophs and PAOs was verified using conventional completely mixed and tanks‐in‐series models. Then, competition was studied in the CFD model. These results demonstrated that PAOs and heterotrophs can theoretically coexist in a single bioreactor when the oxygen input is appropriate to allow sufficient low‐dissolved‐oxygen zones to develop.
New ABCC8 Mutations in Relapsing Neonatal Diabetes and Clinical Features
Authors: Vaxillaire Martine , Dechaume Aurélie , Busiah Kanetee , Cavé Hélène , Pereira Sabrina , Scharfmann Raphael , de Nanclares Guiomar Perez , Castano Luis , Froguel Philippe , Polak Michel ,   and the SUR1–Neonatal Diabetes Study Group
Published: May 2007

Activating mutations in the ABCC8 gene that encodes the sulfonylurea receptor 1 (SUR1) regulatory subunit of the pancreatic islet ATP-sensitive K+ channel (KATP channel) cause both permanent and transient neonatal diabetes. Recently, we have described the novel mechanism where basal Mg-nucleotide–dependent stimulatory action of SUR1 on the Kir6.2 pore is increased. In our present study, we identified six new heterozygous ABCC8 mutations, mainly in patients presenting the transient form of neonatal diabetes (six of eight), with a median duration of initial insulin therapy of 17 months (range 0.5–38.0). Most of these mutations map to key functional domains of SUR1. Whereas Kir6.2 mutations are a common cause of permanent neonatal diabetes and in a few cases associate with the DEND (developmental delay, epilepsy, and neonatal diabetes) syndrome, SUR1 mutations are more frequent in transient (52%) compared with permanent (14%) neonatal diabetes cases screened for ABCC8 in our series. Although ketoacidosis is frequent at presentation, SUR1 mutations associate mainly with transient hyperglycemia, with possible recurrence later in life. One-half of the SUR1 neonatal diabetic patients presented with de novo mutations. In some familial cases, diabetes is not always present in the adult carriers of SUR1 mutations, supporting variability in their clinical expressivity that remains to be fully explained.
What Is the Best Predictor of Future Type 2 Diabetes?
Authors: Abdul-Ghani Muhammad A. , Williams Ken , DeFronzo Ralph A. , Stern Michael
Published: May 2007

OBJECTIVE—We sought to assess insulin secretion/insulin resistance index in predicting the risk for future type 2 diabetes

RESEARCH DESIGN AND METHODS—A total of 1,551 nondiabetic subjects from the San Antonio Heart Study received an oral glucose tolerance test (OGTT) with measurement of plasma glucose and insulin concentrations at 0, 30, 60, and 120 min at baseline and after 7–8 years of follow-up. Insulin secretion/insulin resistance index was calculated as the product of Matsuda index and ΔI0–30/ΔG0–30 or ΔI0–120/ΔG0–120. The discriminatory power of various prediction models for development of type 2 diabetes was tested with the area under the receiver-operating characteristic (ROC) curve.

RESULTS—Insulin secretion/insulin resistance index (0- to 30- and 0- to 120-min time periods) had the greatest areas under the ROC curve (0.85 and 0.86, respectively), which were significantly greater than the 2-h plasma glucose concentration during the OGTT or the San Antonio Diabetes Prediction Model (SADPM) (P < 0.001 and P < 0.0001, respectively). A model based on the combination of the SADPM and a modified version of the insulin secretion/insulin resistance index or 1-h plasma glucose concentration had equal power to predict the risk for future type 2 diabetes compared with the insulin secretion/insulin resistance index.

CONCLUSIONS—The insulin secretion/insulin resistance index is useful as a predictor of future development of type 2 diabetes. A model based on the combination of the SADPM and either a modified version of the insulin secretion/insulin resistance index or 1-h plasma glucose concentration can equally predict future type 2 diabetes.
Vitamin D, Parathyroid Hormone Levels, and the Prevalence of Metabolic Syndrome in Community-Dwelling Older Adults
Authors: Reis Jared P. , von Mühlen Denise , Kritz-Silverstein Donna , Wingard Deborah L. , Barrett-Connor Elizabeth
Published: May 2007

OBJECTIVE—Accumulating research suggests low-circulating vitamin D concentrations, i.e., 25-hydroxyvitamin-D [25(OH)D], may be associated with an increased prevalence of metabolic syndrome; however, previous studies have not accounted for parathyroid hormone (PTH) levels. We examined the association of 25(OH)D and PTH with the prevalence of metabolic syndrome in a community-based cohort of older adults.

RESEARCH DESIGN AND METHODS—Participants included 410 men and 660 women, 44–96 years old, who completed a follow-up clinic visit in 1997–1999 as part of the Rancho Bernardo Study. Sex-specific logistic regression models were fit to estimate the odds of ATP III (Adult Treatment Panel III)-defined metabolic syndrome across quintiles of 25(OH)D and PTH, adjusting for age, season, and major lifestyle factors.

RESULTS—In men, there was a significant trend (P = 0.03) of increasing adjusted odds for metabolic syndrome with increasing PTH concentrations, primarily due to an odds ratio of 2.02 (95% CI 0.96–4.24) in men in the top quintile (≥63 ng/l) of PTH concentration. This association remained unchanged after taking into account 25(OH)D levels and excluding men with diabetes or impaired renal function; it was attenuated after adjustment for the homeostasis model assessment of insulin resistance. Neither PTH in women nor 25(OH)D levels in either sex was related to the metabolic syndrome.

CONCLUSIONS—These findings suggest an increased risk of metabolic syndrome with elevated PTH levels in older men and no effect of 25(OH)D concentrations in either sex. The reason for the sex difference in the PTH–metabolic syndrome association is unknown. Prospective studies are necessary to better determine the roles of 25(OH)D and PTH in the etiology of metabolic syndrome.
Objectively Measured Light-Intensity Physical Activity Is Independently Associated With 2-h Plasma Glucose
Authors: Healy Genevieve N. , Dunstan David W. , Salmon Jo , Cerin Ester , Shaw Jonathan E. , Zimmet Paul Z. , Owen Neville
Published: May 2007

OBJECTIVE—We examined the associations of objectively measured sedentary time, light-intensity physical activity, and moderate- to vigorous-intensity activity with fasting and 2-h postchallenge plasma glucose in Australian adults.

RESEARCH DESIGN AND METHODS—A total of 67 men and 106 women (mean age ± SD 53.3 ± 11.9 years) without diagnosed diabetes were recruited from the 2004–2005 Australian Diabetes, Obesity, and Lifestyle (AusDiab) study. Physical activity was measured by Actigraph accelerometers worn during waking hours for 7 consecutive days and summarized as sedentary time (accelerometer counts/min <100; average hours/day), light-intensity (counts/min 100-1951), and moderate- to vigorous-intensity (counts/min ≥1,952). An oral glucose tolerance test was used to ascertain 2-h plasma glucose and fasting plasma glucose.

RESULTS—After adjustment for confounders (including waist circumference), sedentary time was positively associated with 2-h plasma glucose (b = 0.29, 95% CI 0.11–0.48, P = 0.002); light-intensity activity time (b = −0.25, −0.45 to −0.06, P = 0.012) and moderate- to vigorous-intensity activity time (b = −1.07, −1.77 to −0.37, P = 0.003) were negatively associated. Light-intensity activity remained significantly associated with 2-h plasma glucose following further adjustment for moderate- to vigorous-intensity activity (b = −0.22, −0.42 to −0.03, P = 0.023). Associations of all activity measures with fasting plasma glucose were nonsignificant (P > 0.05).

CONCLUSIONS—These data provide the first objective evidence that light-intensity physical activity is beneficially associated with blood glucose and that sedentary time is unfavorably associated with blood glucose. These objective data support previous findings from studies using self-report measures, and suggest that substituting light-intensity activity for television viewing or other sedentary time may be a practical and achievable preventive strategy to reduce the risk of type 2 diabetes and cardiovascular disease.
Femelschlag oder Plenterung – Ein Vergleich aus betriebswirtschaftlicher Sicht | Irregular Shelterwood System or Selection ('Plenter') System – a Comparison from an Economic Point of View
Authors: Mohr Conradin , Schori Christian
Published: May 2007

The state-owned forest enterprise of the former forest district of Berne introduced cost accounting per forest unit in 1981. The present study compares the irregular shelter-wood units with the selection ('plenter') system units on the basis of important operational parameters. Overall profits from timber production in the selection forest units exceeded those of the irregular shelterwood units by an average of 25 Swiss francs/m3. Selection system unit expenditure was lower by 15 Swiss francs/m3. The selection system has the advantage of incurring substantially lower planting and tending costs whereas timber harvesting costs for both parts of the forest enterprise were about the same. Up until 1991, the selection forests achieved higher yields with an average of 15.– Swiss francs/m3. Due to the decline of the silver fir price, however, there has been no difference in this parameter since 1992. Thus, apart from the advantages of the selection forest regarding ecology and the protection function, economic reasons also support this particular method of treatment.
Ökobilanzierung von forstlichen Produktionssystemen - Beziehungen zu Umweltmanagementsystemen und Übersicht über das methodische Konzept | Life Cycle Analysis of Production Systems in Forestry - Interfaces to Environmental Management Systems and Review of the Methodological Framework
Authors: Heinimann Hans Rudolf
Published: May 2007

The «sustainable development» concept of Rio 1992 has to be realised on an operational level. This paper discusses environmental management systems with components such as Life Cycle Analysis methodology and Assessment of wood as a raw material.
Mechanical strain-induced human vascular matrix synthesis: The role of angiotensin II
Authors: Stanley Adrian G , Patel Hash , Knight Abigail L , Williams Bryan
Published: May 2007

Introduction: Reduced vascular compliance in patients with hypertension results from an increase in extra-cellular matrix (ECM) protein deposition in blood vessels. At least two key factors, namely mechanical strain and neurohumoral mediators, for example Angiotensin II (Ang II), promote fibrogenesis within vessel walls; however potential interactions between these have not been clearly defined. This work examined the direct effect of mechanical strain on matrix mRNA expression and protein synthesis by human vascular smooth muscle (VSM) cells and identified the importance of renin-angiotensin system (RAS) activation in stretch-induced matrix production.

Methods: Human VSM cells were exposed either to a cyclical mechanical strain regimen or to Ang II in the presence or absence of the Ang II receptor (AT1 R) antagonist losartan or its more potent metabolite EXP3174. Analysis of matrix mRNA expression (Northerns) and protein synthesis (ELISA) and cellular AT1-receptor protein expression (Westerns) were determined.

Results: Ang II increased both collagen α1 (92%, SEM +/-20%) mRNA expression and fibronectin (21% +/- 6%) protein synthesis in static VSM cells compared with unstimulated controls.The effect of Ang II was attenuated by antagonism of the AT 1-receptor (AT1 R). Similarly, mechanical strain induced an increase in both collagen α1 (102% +/- 30%) mRNA expression and fibronectin (50% +/-21%) protein synthesis. Surprisingly, in the absence of exogenous Ang II, AT1-receptor blockade attenuated this stretch-induced increase in matrix synthesis. Mechanical strain also induced an increase in total cellular AT1-receptor protein (30.7% +/- 3.5%) compared with static cells.

Conclusion: Both mechanical strain and Ang II increased matrix gene expression and protein synthesis by human VSM cells. The effect of strain was attenuated by AT 1-receptor antagonism. Our results further suggest that mechanical strain may sensitise human VSM cells to the fibrogenic actions of Ang II, perhaps via upregulation of the AT1-receptor.
Combination of non-hypotensive doses of valsartan and enalapril improves survival of spontaneously hypertensive rats with endothelial dysfunction
Authors: Gasparo Marc de , Hess Patrick , Nuesslein-Hildesheim Barbara , Bruneval Patrick , Clozel Jean-Paul
Published: May 2007

There is increasing evidence to suggest endothelial dysfunction as a critical factor in vascular diseases. Genetically predisposed spontaneously hypertensive rats (SHR) treated with inhibitors of nitric oxide (NO) synthase, develop a severe hypertensive nephrosclerosis without the necessity for surgical reduction in renal mass, nephrectomy, renal infarction or nephrotoxic drugs. In these animals, endothelial dysfunction is considered a valid model for assessment of the efficacy of cardiovascular therapy. SHR were treated with either the angiotensin-converting enzyme inhibitor enalapril or the angiotensin II (Ang II) AT1-receptor antagonist (AIIA) valsartan at sub-hypotensive doses and the effects on survival rates, cardiac and renal changes were monitored. Rats treated with valsartan, alone or in combination with enalapril, showed markedly higher survival rates (67—85%, respectively) than untreated animals (37%) or those treated with enalapril alone (55%). Valsartan at a dose which attenuated blood pressure increase led to even greater survival rates (95%). Despite these improved survival rates, at non-hypotensive doses the drugs had no effect on histological appearance, nor was kidney function improved. Plasma creatinine levels were reduced by valsartan, alone or in combination with enalapril, but proteinuria persisted with all treatments over the 12 weeks of the study. Aldosterone levels were significantly reduced by all treatments. The results suggest a beneficial role for endothelium in hypertension. Reduced renal perfusion pressure probably underlies the beneficial renal effects of high-dose valsartan.
Binding characteristics of [3H]-irbesartan to human recombinant angiotensin type 1 receptors
Authors: Vanderheyden Patrick ML , Verheijen Ilse , Fierens Frederik LP , De Backer Jean-Paul , Vauquelin Georges
Published: May 2007

The aim of the present work was to investigate the binding properties of the selective AT1-receptor antagonist irbesartan to human AT1-receptors by direct radioligand binding. For this purpose the specific binding of [3H]-irbesartan to intact Chinese Hamster Ovary (CHO) cells expressing human recombinant AT1-receptors was determined. Specific binding of [3H]-irbesartan rapidly reached equilibrium and was saturable with a KD of 1.94 ± 0.12 to a homogeneous class of binding sites. Its binding was inhibited by other AT1 antagonists (AIIAs) with the same potency order as previous results from [3H]-angiotensin II and [3H]-candesartan binding to human AT1-receptors. Whereas the dissociation rate of [3H]-irbesartan was essentially independent of the radioligand concentration, it was much slower at 12°C when compared with 37°C. Moreover, the dissociation rate was similar, as determined in washout experiments in the absence or presence of unlabelled AT1 antagonists. At 37°C the dissociation rate constant corresponded to a half-life of approximately seven minutes, which is sufficient to explain the partially insurmountable inhibition by irbesartan in previous studies. In contrast, other phenomena such as the plasma half life and tissue-related factors are necessary to explain its sustained in vivo antihypertensive effect.
Losartan reduces sympathetic nerve outflow from the brain of rats with chronic renal failure
Authors: Campese Vito M , Shaohua Ye  , Truong Rex H , Gamburd Michael
Published: May 2007

Sympathetic nervous system (SNS) activity, measured by norepinephrine (NE) turnover rate, was greater in the posterior hypothalamic (PH) nuclei, the paraventricular nuclei (PVN), and the locus coeruleus (LC) of 5/6 nephrectomised (CRF) rats than of control rats. NE secretion from the PH was also greater in CRF than in control rats. These findings demonstrate that SNS activity plays an important role in the genesis of hypertension associated with CRF. The increase in central SNS activity was mitigated by increased local expression of nitric oxide synthase (NOS)-mRNA and nitric oxide (NOx) production. Because angiotensin II may stimulate the central SNS, we tested the hypothesis that losartan, a specific angiotensin II AT1-receptor antagonist, may lower blood pressure (BP), at least in part, by central noradrenergic inhibition. To this end, we studied two groups of CRF rats. One group received losartan (10 mg/kg body weight) in drinking water between the 3rd and 4th week after nephrectomy, the second group received drinking water without losartan. SNS activity was measured by NE secretion from the PH using the microdialysis technique. NOS-mRNA gene expression was also measured by RT-PCR in the PH, PVN, and LC of CRF and control rats. Losartan reduced systolic BP from 184±3.7 to 152±3.1 mmHg and NE secretion from the PH from 340±9.7 to 247±4.8 pg/ml. CRF rats treated with losartan manifested a significant (p<0.01) increase in the expression of nNOS-mRNA in the PH (from 84±1.2 to 99±2.6), the PVN (from 44±1.5 to 63±2.1), and the LC (from 59±6.7 to 76±2.1). CRF rats also manifested a significant increase (p<0.01) in the expression of IL-1β in the PH (from 41.6±2.8 to 54.3±1.4), PVN (from 44±1.9 to 54±1.5), and LC (from 35.5±1.6 to 53.5±1.9).

In conclusion, these studies suggest that the antihypertensive action of losartan in CRF rats may be mediated, at least in part, by inhibition of central SNS outflow. The studies also suggest that the inhibitory action of losartan on the SNS may be mediated by activation of IL-1β, which, in turn, stimulates nNOS, an important modulator of central SNS activity.
Hypertension and its management: A problem in need of new treatment strategies
Authors: Neutel Joel M
Published: May 2007

Although treatments of hypertension have significantly decreased morbidity and mortality from cerebrovascular disease, the associated reductions in coronary artery disease have been very disappointing. Hypertension is a complex inherited syndrome of cardiovascular risk factors, all of which contribute to the development of heart disease. Angiotensin II receptor blockers (ARBs), such as the highly selective ARB valsartan, provide an alternative treatment strategy to address the multiple issues in coronary artery disease. These agents are well-tolerated and have a once-daily regimen that improves compliance. They bring multiple cardiovascular benefits beyond blood pressure (BP) control, such as renoprotection and cardiovascular growth reduction.
Cardiac, renal and vascular complications in the diabetic patient
Authors: Zanchetti Alberto
Published: May 2007

Type 2 diabetes has long been known to be associated with an increased risk of cardiovascular disease. Patients with type 2 diabetes have also been shown to benefit more from antihypertensive therapy than do non-diabetics with hypertension. The benefits of aggressive antihypertensive therapy are reflected in the recent reduction of blood pressure (BP) targets in international guidelines. Drugs acting on the renin-angiotensin-aldosterone system (RAAS) have well-documented efficacy, and results from large-scale trials with highly selective angiotensin II (Ang II) receptor blockers (ARBs), such as valsartan, are awaited. The VALUE trial will provide the largest body of information yet on the comparative benefits of using an ARB or calcium channel blocker in hypertensive patients with diabetes.
New clinical investigations with selective angiotensin II receptor blocker therapy in diabetes and renal disease
Authors: Ruilope Luis M
Published: May 2007

Halting the reduction in glomerular filtration rate (GFR) is the primary aim of any treatment of patients presenting with progressive chronic renal failure, a very common corollary to diabetes. To improve GFR, the high blood pressure (BP) and proteinuria often seen in these patients must both be controlled. These symptoms lead not only to progressive loss of renal function, but also to an increase in cardiovascular risk. Use of angiotensin-converting enzyme (ACE) inhibitors in these patients has been reported to control BP and reduce protein excretion and cardiovascular risk. Complete blockade of angiotensin II (Ang II) action with the highly selective Ang II receptor blocker (ARB) valsartan, both as monotherapy and in combination with ACE inhibitors, is well-tolerated and efficacious in patients with renal failure. Unlike ACE inhibition, ARB treatment leads to no initial reduction in GFR, thus valsartan may be a better agent for the control of BP, with greater renal protection.
Pathological involvement of chymase-dependent angiotensin II formation in the development of cardiovascular disease
Authors: Urata Hidenori
Published: May 2007

Chymase is a potent and specific angiotensin II (Ang II)-forming enzyme in vitro. There is also strong evidence to suggest its importance in vivo. Recent clinical studies have suggested that high serum cholesterol levels are associated with increased vascular chymase activity and this may assist in the development of atherosclerosis. This clinical finding has been reproduced in hamster models. Studies with transgenic mice overexpressing the human chymase gene suggest a direct association between vascular chymase upregulation and atherogenesis. There is also increased chymase activity following various cardiac diseases such as myocardial ischaemia, volume overload cardiac failure, cardiomyopathy and viral myocarditis, suggesting that increased cardiac chymase activity appears to be involved in cardiac remodelling.
The renin-angiotensin-aldosterone system is suppressed in adults with Type 1 diabetes
Authors: Bojestig Mats , Nystrom Fredrik H , Arnqvist Hans J , Ludvigsson Johnny , Karlberg Bengt E
Published: May 2007

Poor glycaemic control and high blood pressure are two important risk factors for the development of retinopathy and nephropathy in Type 1 diabetes. The renin-angiotensin-aldosterone system (RAAS) may be involved in this process, since treatment with angiotensin-converting enzyme (ACE) inhibitors postpones the development of these complications. We investigated whether plasma renin activity (PRA), plasma angiotensin II (Ang II) and atrial natriuretic peptide (ANP) differed in Type 1 diabetic patients compared with healthy controls. We recruited 80 patients with Type 1 diabetes of more than 10 years' duration and 75 age-matched controls. We found that PRA and Ang II concentrations were significantly lower in patients than in the controls. The levels of ANP, on the other hand, were higher in patients than in controls. PRA correlated negatively to the mean value of HbA1c during the previous five years. PRA and Ang II were significantly lower in patients with mean HbA1c >8.4% compared with those with mean HbA1c <7.2%. In summary, we found patients with Type 1 diabetes to have RAAS suppression and increased ANP levels, suggesting a state of fluid retention.
Should the use of short acting angiotensin-converting enzyme inhibitors be abandoned?
Authors: Erman Arie , Boner Geoffrey , van Dijk David J
Published: May 2007

Background Angiotensin-converting enzyme inhibitors (ACE-I) have different modes of action and different durations of inhibition. The effects of ACE-I on the various components of the renin-angiotensin system (RAS) at trough hours were studied in patients with diabetes mellitus receiving long-term ACE-I treatment.

Methods Out of 86 Type 1 and 2 diabetic patients, 49 were untreated, 25 received captopril and 12 received enalapril as chronic treatment. Blood for the determination of plasma renin activity (PRA), serum ACE activity and plasma angiotensin II (Ang II) was drawn in the morning (0700—0900 hours) after an overnight fast, about 12 hours after the last dose. PRA and Ang II were measured by RIA and serum ACE activity was assayed by a radiometric assay using 3H-hippuryl-glycyl-glycine as a substrate.

Results Mean age was significantly greater in the enalapril-treated patients. Systolic and diastolic blood pressures were not different between the captopril-treated and untreated groups. Serum ACE activity in the captopril-treated diabetic patients was 101.5±42.5 nmol/mL/min, values obtained in untreated diabetic patients (101.4±25.2 nmol/mL/min). In contrast, ACE activity in the enalapril-treated patients was significantly reduced (5.5±7.5 nmol/mL/min) compared with untreated and captopril-treated patients (p<0.00001). PRA values in the ACE-I treated patients were significantly increased. Plasma Ang II levels were significantly increased in the captopril-treated vs. untreated patients (65.1±50.2 vs. 36.2±31.7 pg/mL, p=0.006), whereas the values in the enalapril-treated patient were slightly, but not significantly, reduced (23.8±21.4 pg/mL).

Conclusion Trough serum ACE activity is not suppressed in diabetic patients receiving captopril, compared with those receiving enalapril and we thus question the use of short acting ACE-I in these patients.