bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Soluble Guanylate Cyclase–Dependent Mechanism Is Involved in the Regulation of Net Hepatic Glucose Uptake by Nitric Oxide in Vivo
Authors: An Zhibo , Winnick Jason J. , Farmer Ben , Neal Doss , Lautz Margaret , Irimia Jose M. , Roach Peter J. , Cherrington Alan D. 
Published: September 2010

OBJECTIVEWe previously showed that elevating hepatic nitric oxide (NO) levels reduced net hepatic glucose uptake (NHGU) in the presence of portal glucose delivery, hyperglycemia, and hyperinsulinemia. The aim of the present study was to determine the role of a downstream signal, soluble guanylate cyclase (sGC), in the regulation of NHGU by NO.RESEARCH DESIGN AND METHODSStudies were performed on 42-h–fasted conscious dogs fitted with vascular catheters. At 0 min, somatostatin was given peripherally along with 4× basal insulin and basal glucagon intraportally. Glucose was delivered at a variable rate via a leg vein to double the blood glucose level and hepatic glucose load throughout the study. From 90 to 270 min, an intraportal infusion of the sGC inhibitor 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) was given in −sGC (n = 10) and −sGC/+NO (n = 6), whereas saline was given in saline infusion (SAL) (n = 10). The −sGC/+NO group also received intraportal SIN-1 (NO donor) to elevate hepatic NO from 180 to 270 min.RESULTSIn the presence of 4× basal insulin, basal glucagon, and hyperglycemia (2× basal ), inhibition of sGC in the liver enhanced NHGU (mg/kg/min; 210–270 min) by ∼55% (2.9 ± 0.2 in SAL vs. 4.6 ± 0.5 in −sGC). Further elevating hepatic NO failed to reduce NHGU (4.5 ± 0.7 in −sGC/+NO). Net hepatic carbon retention (i.e., glycogen synthesis; mg glucose equivalents/kg/min) increased to 3.8 ± 0.2 in −sGC and 3.8 ± 0.4 in −sGC/+NO vs. 2.4 ± 0.2 in SAL (P &lt; 0.05).CONCLUSIONSNO regulates liver glucose uptake through a sGC-dependent pathway. The latter could be a target for pharmacologic intervention to increase meal-associated hepatic glucose uptake in individuals with type 2 diabetes.
Maternal Antioxidant Supplementation Prevents Adiposity in the Offspring of Western Diet–Fed Rats
Authors: Sen Sarbattama , Simmons Rebecca A. 
Published: September 2010

OBJECTIVE
Obesity in pregnancy significantly increases the risk of the offspring developing obesity after birth. The aims of this study were to test the hypothesis that maternal obesity increases oxidative stress during fetal development, and to determine whether administration of an antioxidant supplement to pregnant Western diet-fed rats would prevent the development of adiposity in the offspring.

RESEARCH DESIGN AND METHODS
Female Sprague Dawley rats were started on the designated diet at 4 weeks of age. Four groups of animals were studied: control chow (control); control + antioxidants (control+Aox); Western diet (Western); and Western diet + antioxidants (Western+Aox). The rats were mated at 12 to 14 weeks of age, and all pups were weaned onto control diet.

RESULTS
Offspring from dams fed the Western diet had significantly increased adiposity as early as 2 weeks of age as well as impaired glucose tolerance compared with offspring of dams fed a control diet. Inflammation and oxidative stress were increased in preimplantation embryos, fetuses, and newborns of Western diet-fed rats. Gene expression of proadipogenic and lipogenic genes was altered in fat tissue of rats at 2 weeks and 2 months of age. The addition of an antioxidant supplement decreased adiposity and normalized glucose tolerance.

CONCLUSIONS
Inflammation and oxidative stress appear to play a key role in the development of increased adiposity in the offspring of Western diet-fed pregnant dams. Restoration of the antioxidant balance during pregnancy in the Western diet-fed dam is associated with decreased adiposity in offspring.
High Glucose Increases Lysyl Oxidase Expression and Activity in Retinal Endothelial Cells: Mechanism for Compromised Extracellular Matrix Barrier Function
Authors: Chronopoulos Argyrios , Tang Amanda , Beglova Ekaterina , Trackman Philip C. , Roy Sayon 
Published: September 2010

OBJECTIVE
In diabetes, retinal vascular basement membrane (BM) undergoes significant thickening and compromises vessel function including increased vascular permeability, a prominent lesion of early diabetic retinopathy. In this study we determined whether altered expression and activity of lysyl oxidase (LOX), a cross-linking enzyme, may compromise vascular basement membrane functional integrity under high-glucose (HG) conditions.

RESEARCH DESIGN AND METHODS
Rat retinal endothelial cells (RRECs) grown in normal (5 mmol/l) or HG (30 mmol/l glucose) medium for 7 days were assessed for expression of LOX and proLOX by Western blot analysis and LOX enzyme activity. To determine whether HG alters cellular distribution patterns of LOX and proLOX, immunostaining with respective antibodies was performed. Similarly, cells grown in normal or HG medium were subjected to both LOX inhibition with β-aminopropionitrile (BAPN) and by small interfering RNA knockdown, and respectively examined for cell monolayer permeability. Additionally, retinas of streptozotocin (STZ)-induced diabetic rats were analyzed to determine if diabetes altered LOX expression.

RESULTS
Western blot analysis revealed significantly increased LOX and proLOX expression in cells grown in HG medium compared with those grown in normal medium. The increased LOX level was strikingly similar to LOX upegulation in the diabetic retinas. In cells grown in HG medium, LOX activity and cell monolayer permeability was significantly increased, as were LOX and proLOX immunostaining. Small interfering RNA- or BAPN–induced-specific blockage of LOX expression or activity, respectively, reduced cell monolayer permeability.

CONCLUSIONS
HG-induced increased LOX expression and activity compromises barrier functional integrity, a prominent lesion of diabetic retinopathy.
Smoking and Risk for Diabetes Incidence and Mortality in Korean Men and Women
Authors: Jee Sun Ha , Foong Athena W. , Hur Nam Wook , Samet Jonathan M. 
Published: September 2010

OBJECTIVE
Mounting evidence suggests that smoking is a cause of type 2 diabetes. We explored the association of cigarette smoking with diabetes incidence and mortality in a large cohort of Koreans.

RESEARCH DESIGN AND METHODS
A 14-year prospective cohort study was performed on 1,236,443 Korean men and women, aged 30–95 years at baseline, who underwent standardized biennial medical examinations provided by the National Health Insurance Corporation (NHIC). Incident diabetes was identified on the basis of outpatient visits, hospitalization, or prescription medication treatment for diabetes, as captured in the NHIC database. Diabetes mortality was obtained through the national statistical office. Cox proportional hazards models were used to investigate associations of smoking with indicators of diabetes and diabetes mortality.

RESULTS
Smoking was significantly associated with increased risk for diabetic outpatient treatment, hospitalization, and mortality among both men and women, and the risk among current smokers increased modestly with the number of cigarettes smoked daily (Ptrend &lt; 0.0001 for all associations). Compared with never smokers, current male smokers who smoked ≥20 cigarettes/day had increased risk for incident diabetes defined by outpatient treatment (adjusted hazard ratio 1.55 [1.51–1.60]), incident diabetes defined by ≥3 prescription medications for diabetes (1.71 [1.63–1.80]), and death from diabetes (1.60 [1.25–2.06]). The risks for outpatient treatment among smokers were higher in men than in women with evidence for effect modification by sex and age (Pinteraction &lt; 0.0001).

CONCLUSIONS
Our study provides longitudinal evidence that smoking increases the risk of incident diabetes and mortality.
Patient Age, Ethnicity, Medical History, and Risk Factor Profile, but Not Drug Insurance Coverage, Predict Successful Attainment of Glycemic Targets
Authors: Teoh Hwee , Braga Manoela F.B. , Casanova Amparo , Drouin Denis , Goodman Shaun G. , Harris Stewart B. , Langer Anatoly , Tan Mary K. , Ur Ehud , Yan Andrew T. , Zinman Bernard , Leiter Lawrence A. ,   on behalf of the T2DM QUERI Investigators
Published: September 2010

OBJECTIVE
To identify factors in patients with type 2 diabetes and A1C &gt;7.0% associated with attainment of A1C ≤7.0%.

RESEARCH DESIGN AND METHODS
We used a prospective registry of 5,280 Canadian patients in primary care settings enrolled in a 12-month glycemic pharmacotherapy optimization strategy based on national guidelines.

RESULTS
At close out, median A1C was 7.1% (vs. 7.8% at baseline) with 48% of subjects achieving A1C ≤7.0% (P &lt; 0.0001). Older patients of Asian or black origin, those with longer diabetes duration, those with lower baseline A1C, BMI, LDL cholesterol, and blood pressure, and those on angiotensin receptor blockers and a lower number of antihyperglycemic agents, were more likely to achieve A1C ≤7.0% at some point during the study (all P &lt; 0.0235). Access to private versus public drug coverage did not impact glycemic target realization.

CONCLUSIONS
Patient demography, cardiometabolic health, and ongoing pharmacotherapy, but not access to private drug insurance coverage, contribute to the care gap in type 2 diabetes.
Low Peripheral Nerve Conduction Velocities and Amplitudes Are Strongly Related to Diabetic Microvascular Complications in Type 1 Diabetes
Authors: Charles Morten , Soedamah-Muthu Sabita S. , Tesfaye Solomon , Fuller John H. , Arezzo Joseph C. , Chaturvedi Nishi , Witte Daniel R. ,   EURODIAB Prospective Complications Study Investigators
Published: September 2010

OBJECTIVE
Slow nerve conduction velocity and reduction in response amplitude are objective hallmarks of diabetic sensorimotor polyneuropathy. Because subjective or clinical indicators of neuropathy do not always match well with the presence of abnormal nerve physiology tests, we evaluated associations to nerve conduction in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS
Nerve conduction studies were performed in the distal sural and ulnar sensory nerves and the peroneal motor nerve in 456 individuals with type 1 diabetes who participated in the follow-up visit of the EURODIAB Prospective Complications Study (EPCS). We used multivariate regression models to describe associations to decreased nerve conduction measures.

RESULTS
In addition to an effect of duration of diabetes and A1C, which were both associated with low nerve conduction velocity and response amplitude, we found that the presence of nephropathy, retinopathy, or a clinical diagnosis of neuropathy was associated with low nerve conduction velocity and amplitude. In the case of nonproliferative retinopathy, the odds ratio (OR) for being in lowest tertile was 2.30 (95% CI 1.13–4.67) for nerve conduction velocity. A similar OR was found for each 2% difference in A1C (2.39 [1.68–3.41]).

CONCLUSIONS
We show that the presence of other microvascular diabetes complications, together with diabetes duration and A1C, are associated with low nerve conduction velocity and amplitude response and that cardiovascular disease or risk factors do not seem to be associated with these measures.
Preterm Birth—A Risk Factor for Type 2 Diabetes?
Authors: Kajantie Eero , Osmond Clive , Barker David J.P. , Eriksson Johan G. 
Published: September 2010

OBJECTIVE
The association between low birth weight and type 2 diabetes is well established. We studied whether preterm birth carries a similar risk.

RESEARCH DESIGN AND METHODS
The Helsinki Birth Cohort includes 13,345 men and women born between 1934 and 1944. Of them, 12,813 had adequate data on length of gestation, which we linked with data on special reimbursement for diabetes medication.

RESULTS
Of the subjects, 5.1% had received special reimbursement after age 40. In subjects born before 35 weeks of gestation, the odds ratio for diabetes was 1.68 (95% CI 1.06–2.65) compared with that in those born at term. After adjustment for birth weight relative to length of gestation, the odds ratio was 1.59 (1.00–2.52).

CONCLUSIONS
Preterm birth before 35 weeks of gestation is associated with an increased risk of type 2 diabetes in adult life. The risk is independent of that associated with slow fetal growth.
Effects of Thyroid Hormone on A1C and Glycated Albumin Levels in Nondiabetic Subjects With Overt Hypothyroidism
Authors: Kim Mee Kyoung , Kwon Hyuk Sang , Baek Ki-Hyun , Lee Je Hoon , Park Woo Chan , Sohn Hyung Sun , Lee Kwang-Woo , Song Ki-Ho 
Published: September 2010

OBJECTIVE
We aimed to determine the effects of thyroid hormone on A1C and glycated albumin (GA) in nondiabetic patients with overt hypothyroidism.

RESEARCH DESIGN AND METHODS
A1C levels were measured in 45 nondiabetic patients with overt hypothyroidism and 180 euthyroid control subjects. A1C, GA, fasting blood glucose (FBG), 1,5-anhydroglucitol, and erythrocyte indexes were determined in 30 nondiabetic patients with overt hypothyroidism before and after thyroid hormone replacement.

RESULTS
A1C levels were higher in patients with hypothyroidism compared with control subjects. A1C levels were decreased by thyroid hormone replacement. Thyroid hormone replacement increased serum erythropoietin, reticulocyte count, and mean corpuscular hemoglobin (MCH). The change in A1C level was significantly correlated with the change in reticulocyte count or MCH. Thyroid hormone replacement decreased serum levels of albumin and GA. However, FBG and 1,5-anhydroglucitol levels were not altered.

CONCLUSIONS
Levels of A1C and GA are spuriously high in nondiabetic patients with overt hypothyroidism.
Synthesis of Glycerol Nucleic Acid (GNA) Phosphoramidite Monomers and Oligonucleotide Polymers
Authors: Zhang Su , Chaput John C. 
Published: September 2010

AbstractThis unit describes a straightforward method for preparing glycerol nucleic acid (GNA) phosphoramidite monomers and oligonucleotide polymers using standard cyanoethyl phosphoramidite chemistry. GNA is an unnatural nucleic acid analog composed of an acyclic three‐carbon sugar‐phosphate backbone that contains one stereogenic center per repeating unit. GNA has attracted significant attention as a nucleic acid derivative due to its unique ability to form stable Watson‐Crick anti‐parallel duplex structures with thermal and thermodynamic stabilities rivaling those of natural DNA and RNA. The chemical simplicity of this nucleic acid structure provides access to enantiomerically pure forms of right‐ and left‐handed helical structures that can be used as unnatural building blocks in DNA nanotechnology. Curr. Protoc. Nucleic Acid Chem. 42:4.40.1‐4.40.18. © 2010 by John Wiley & Sons, Inc.
Obesity and its measurement in a community‐based sample of women with systemic lupus erythematosus
Authors: Katz Patricia , Gregorich Steven , Yazdany Jinoos , Trupin Laura , Julian Laura , Yelin Edward , Criswell Lindsey A. 
Published: September 2010

AbstractObjectiveTo determine the prevalence of obesity and evaluate how accurately standard anthropometric measures identify obesity among women with systemic lupus erythematosus (SLE).MethodsDual x‐ray absorptiometry (DXA), height, weight, and waist and hip circumference measurements were collected from 145 women with SLE. Three anthropometric proxies of obesity (body mass index [BMI] ≥30 kg/m2, waist circumference [WC] ≥88 cm, and waist:hip ratio [WHR] ≥0.85) were compared with a DXA‐based obesity criterion. Correspondence between measures was assessed with Cohen's kappa. Receiver operating characteristic curves determined optimal cut points for each anthropometric measure relative to DXA. Framingham cardiovascular risk scores were compared among women who were classified as not obese by both traditional and revised anthropometric definitions, obese by both definitions, and obese only by the revised definition.ResultsOf the 145 women, 28%, 29%, 41%, and 50% were classified as obese by WC, BMI, WHR, and DXA, respectively. Correspondence between anthropometric and DXA‐based measures was moderate. Women misclassified by anthropometric measures had less truncal fat and more appendicular lean and fat mass. Cut points were identified for anthropometric measures to better approximate DXA estimates of percent body fat: BMI ≥26.8 kg/m2, WC ≥84.75 cm, and WHR ≥0.80. Framingham risk scores were significantly higher in women classified as obese by either traditional or revised criteria.ConclusionA large percentage of this group of women with SLE was obese. Substantial portions of women were misclassified by anthropometric measures. Utility of revised cut points compared with traditional cut points in identifying risk of cardiovascular disease or disability remains to be examined in prospective studies, but results from the Framingham risk score analysis suggest that traditional cut points exclude a significant number of at‐risk women with SLE.
Socioeconomic determinants of disability and depression in patients with rheumatoid arthritis
Authors: Margaretten M. , Barton J. , Julian L. , Katz P. , Trupin L. , Tonner C. , Graf J. , Imboden J. , Yelin E. 
Published: September 2010

AbstractObjectiveTo examine the relationship between functional limitation, socioeconomic inequality, and depression in a diverse cohort of patients with rheumatoid arthritis (RA).MethodsThe study design was cross‐sectional and subjects were from the University of California, San Francisco RA Cohort. Patients were enrolled from 2 rheumatology clinics, an urban county public hospital and a university tertiary care medical center. Age, sex, race/ethnicity, disease activity, functional limitation, and medications were variables collected at clinical visits. The patient's clinic site was used as a proxy for his or her socioeconomic status. The outcome variable was depressive symptom severity measured by the Patient Health Questionnaire 9. Differences in characteristics between depressed and nondepressed patients were calculated using 2‐sided t‐tests or the Pearson's chi‐square test. For the multivariate analysis, repeated measures with generalized estimating equations were used.ResultsThere were statistically significant differences between depressed and nondepressed patients related to race/ethnicity, public versus tertiary care hospital rheumatology clinic, disability, and medications. In the multivariate analysis, increased functional limitation and public clinic site remained significantly associated with increased depression scores. A significant interaction existed between clinic site and disability. Mean depression scores rose more precipitously as functional limitation increased at the public hospital rheumatology clinic.ConclusionThere are disparities in both physical and mental health among individuals with low socioeconomic status. The psychological effects of disability vary in patients with RA such that a vulnerable population with functional limitations is at higher risk of developing depressive symptoms.
Surface Functionalized Colloidal Microparticles for Fast Endocytotic Cell Uptake
Authors: Reibetanz Uta , Lessig Jaqueline , Hoyer Jan , Neundorf Ines 
Published: September 2010

AbstractAim of this study is to enhance fast and effective endocytotic uptake of protamine sulfate and dextran sulfate layer‐by‐layer(LbL) coated silica microparticles by specific functionalization with a cell‐penetrating peptide (CPP) surface layer. CPP are known to act as efficient carriers for a wide range of different substances. By coupling CPP to a given compound, the overall cellular uptake can be increased. Coating and stability of the cell‐penetrating peptide (CPP) layer among different conditions are tested by means of fluorescence markers. Furthermore, the quality of the preparation regarding particle aggregation after peptide coating is explored. After 0.5–2 h cell/particle incubation, the number of cells with peptide‐coated particles in endolysosomes is significantly increased related to particles coated with the positively charged biopolymer protamine sulfate (PRM) on top. Thus, our new designed particles functionalized with CPPs are very useful as fast carriers for active agents addressing the endolysosomal compartment of cells.
Biomimetic Collagen Nanofibrous Materials for Bone Tissue Engineering
Authors: Zheng Wenfu , Zhang Wei , Jiang Xingyu 
Published: September 2010

AbstractHierarchical assemblies of nanofibres are ubiquitous in nature. Mineralized type I collagen is the basic building block of hierarchically organized, highly complex structures of bone tissue. As a biomaterial, collagen is widely utilized in biomimetic nanofibrous matrix fabrication due to its inherent biocompatibility and widespread occurrence in nature. Nanotechnology has recently gained a new impetus due to the introduction of the concept of biomimetic nanofibres for tissue regeneration. The emergence of electrospinning techniques provides a new opportunity to fabricate nano‐collagen fibres for bone tissue engineering. By orchestrating major parameters, collagen fibres with different components (pure or blended), sizes (nanometre to micrometre) and surface properties (mineralized or modified by functional bioactive molecules) have been developed and their effects on bone cell adhesion, proliferation, migration and differentiation evaluated. This review briefly introduces natural mineralized collagen structures in bone, biomimetic mineralization and bone grafts, and in vitro mineralization of collagen nanofibres fabricated by using three major techniques – molecular self‐assembly, electrospinning, and phase separation. Their applications in bone tissue engineering are also discussed. We highlight the electrospinning technique in collagen nanofibre fabrication and its great potential for bone tissue regeneration.
Temperature‐Responsive Controlled Drug Delivery System Based on Titanium Nanotubes
Authors: Cai Kaiyong , Jiang Feng , Luo Zhong , Chen Xiuyong 
Published: September 2010

AbstractIn this study, we reported a smart temperature‐sensitive drug release system based on titanium nanotubes. Titanium nanotubes were fabricated with an electrochemical approach. The 3‐trimethoxysilyl propylmethacrylate (MPS) was initially coupling to the surfaces of titanium nanotubes, and then polymerizing with N‐isopropylacrylamide (NIPAAm) and acrylamide (AAm) to form a hydrogel covering layer. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were employed to characterize the titanium nanotubes drug delivery systems. SEM images revealed that titanium nanotubes had relatively uniform distribution in diameters (52 ± 9 nm) and around 410 nm in length. FTIR spectra suggested that MPS was immobilized and in turn triggering the formation of PNIPAAm/PAAm network onto the surfaces of titanium nanotubes. Drug release profiles indicated that a temperature‐responsive controlled drug release system based on titanium nanotubes was achieved. This study provides alternative for developing novel implantable controlled drug delivery systems from titanium nanotubes.