bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Kallikrein Mediates Retinal Vascular Dysfunction and Induces Retinal Thickening in Diabetic Rats
Authors: Clermont Allen , Chilcote Tamie J. , Kita Takeshi , Liu Jia , Riva Priscilla , Sinha Sukanto , Feener Edward P. 
Published: March 2011

OBJECTIVE
Plasma kallikrein (PK) has been identified in vitreous fluid obtained from individuals with diabetic retinopathy and has been implicated in contributing to retinal vascular dysfunction. In this report, we examined the effects of PK on retinal vascular functions and thickness in diabetic rats.

RESEARCH DESIGN AND METHODS
We investigated the effects of a selective PK inhibitor, ASP-440, and C1 inhibitor (C1-INH), the primary physiological inhibitor of PK, on retinal vascular permeability (RVP) and hemodynamics in rats with streptozotocin-induced diabetes. The effect of intravitreal PK injection on retinal thickness was examined by spectral domain optical coherence tomography.

RESULTS
Systemic continuous administration of ASP-440 for 4 weeks initiated at the time of diabetes onset inhibited RVP by 42% (P = 0.013) and 83% (P &lt; 0.001) at doses of 0.25 and 0.6 mg/kg per day, respectively. Administration of ASP-440 initiated 2 weeks after the onset of diabetes ameliorated both RVP and retinal blood flow abnormalities in diabetic rats measured at 4 weeks’ diabetes duration. Intravitreal injection of C1-INH similarly decreased impaired RVP in rats with 2 weeks’ diabetes duration. Intravitreal injection of PK increased both acute RVP and sustained focal RVP (24 h postinjection) to a greater extent in diabetic rats compared with nondiabetic control rats. Intravitreal injection of PK increased retinal thickness compared with baseline to a greater extent (P = 0.017) in diabetic rats (from 193 ± 10 μm to 223 ± 13 μm) compared with nondiabetic rats (from 182 ± 8 μm to 193 ± 9 μm).

CONCLUSIONS
These results show that PK contributes to retinal vascular dysfunctions in diabetic rats and that the combination of diabetes and intravitreal injection of PK in rats induces retinal thickening.
Associations of Common Genetic Variants With Age-Related Changes in Fasting and Postload Glucose
Authors: Jensen Anders C. , Barker Adam , Kumari Meena , Brunner Eric J. , Kivimäki Mika , Hingorani Aroon D. , Wareham Nicholas J. , Tabák Adam G. , Witte Daniel R. , Langenberg Claudia 
Published: March 2011

OBJECTIVE
In the general, nondiabetic population, fasting glucose increases only slightly over time, whereas 2-h postload glucose shows a much steeper age-related rise. The reasons underlying these different age trajectories are unknown. We investigated whether common genetic variants associated with fasting and 2-h glucose contribute to age-related changes of these traits.

RESEARCH DESIGN AND METHODS
We studied 5,196 nondiabetic participants of the Whitehall II cohort (aged 40–78 years) attending up to four 5-yearly oral glucose tolerance tests. A genetic score was calculated separately for fasting and 2-h glucose, including 16 and 5 single nucleotide polymorphisms, respectively. Longitudinal modeling with age centered at 55 years was used to study the effects of each genotype and genetic score on fasting and 2-h glucose and their interactions with age, adjusting for sex and time-varying BMI.

RESULTS
The fasting glucose genetic score was significantly associated with fasting glucose with a 0.029 mmol/L (95% CI 0.023–0.034) difference (P = 2.76 × 10−21) per genetic score point, an association that remained constant over time (age interaction P = 0.17). Two-hour glucose levels differed by 0.076 mmol/L (0.047–0.105) per genetic score point (P = 3.1 × 10−7); notably, this effect became stronger with increasing age by 0.006 mmol/L (0.003–0.009) per genetic score point per year (age interaction P = 3.0 × 10−5), resulting in diverging age trajectories by genetic score.

CONCLUSIONS
Common genetic variants contribute to the age-related rise of 2-h glucose levels, whereas associations of variants for fasting glucose are constant over time, in line with stable age trajectories of fasting glucose.
Inherited Variation in Vitamin D Genes Is Associated With Predisposition to Autoimmune Disease Type 1 Diabetes
Authors: Cooper Jason D. , Smyth Deborah J. , Walker Neil M. , Stevens Helen , Burren Oliver S. , Wallace Chris , Greissl Christopher , Ramos-Lopez Elizabeth , Hyppönen Elina , Dunger David B. , Spector Timothy D. , Ouwehand Willem H. , Wang Thomas J. , Badenhoop Klaus , Todd John A. 
Published: March 2011

OBJECTIVE
Vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] &lt;50 nmol/L) is commonly reported in both children and adults worldwide, and growing evidence indicates that vitamin D deficiency is associated with many extraskeletal chronic disorders, including the autoimmune diseases type 1 diabetes and multiple sclerosis.

RESEARCH DESIGN AND METHODS
We measured 25(OH)D concentrations in 720 case and 2,610 control plasma samples and genotyped single nucleotide polymorphisms from seven vitamin D metabolism genes in 8,517 case, 10,438 control, and 1,933 family samples. We tested genetic variants influencing 25(OH)D metabolism for an association with both circulating 25(OH)D concentrations and disease status.

RESULTS
Type 1 diabetic patients have lower circulating levels of 25(OH)D than similarly aged subjects from the British population. Only 4.3 and 18.6% of type 1 diabetic patients reached optimal levels (≥75 nmol/L) of 25(OH)D for bone health in the winter and summer, respectively. We replicated the associations of four vitamin D metabolism genes (GC, DHCR7, CYP2R1, and CYP24A1) with 25(OH)D in control subjects. In addition to the previously reported association between type 1 diabetes and CYP27B1 (P = 1.4 × 10−4), we obtained consistent evidence of type 1 diabetes being associated with DHCR7 (P = 1.2 × 10−3) and CYP2R1 (P = 3.0 × 10−3).

CONCLUSIONS
Circulating levels of 25(OH)D in children and adolescents with type 1 diabetes vary seasonally and are under the same genetic control as in the general population but are much lower. Three key 25(OH)D metabolism genes show consistent evidence of association with type 1 diabetes risk, indicating a genetic etiological role for vitamin D deficiency in type 1 diabetes.
Antidiabetic Actions of Endogenous and Exogenous GLP-1 in Type 1 Diabetic Patients With and Without Residual β-Cell Function
Authors: Kielgast Urd , Holst Jens J. , Madsbad Sten 
Published: March 2011

OBJECTIVE
To investigate the effect of exogenous as well as endogenous glucagon-like peptide 1 (GLP-1) on postprandial glucose excursions and to characterize the secretion of incretin hormones in type 1 diabetic patients with and without residual β-cell function.

RESEARCH DESIGN AND METHODS
Eight type 1 diabetic patients with (T1D+), eight without (T1D−) residual β-cell function, and eight healthy matched control subjects were studied during a mixed meal with concomitant infusion of GLP-1 (1.2 pmol/kg/min), saline, or exendin 9-39 (300 pmol/kg/min). Before the meal, half dose of usual fast-acting insulin was injected. Plasma glucose (PG), glucagon, C-peptide, total GLP-1, intact glucose-dependent insulinotropic polypeptide (GIP), free fatty acids, triglycerides, and gastric emptying rate (GE) by plasma acetaminophen were measured.

RESULTS
Incretin responses did not differ between patients and control subjects. Infusion of GLP-1 decreased peak PG by 45% in both groups of type 1 diabetic patients. In T1D+ patients, postprandial PG decreased below fasting levels and was indistinguishable from control subjects infused with saline. In T1D− patients, postprandial PG remained at fasting levels. GLP-1 infusion reduced GE and glucagon levels in all groups and increased fasting C-peptide in T1D+ patients and control subjects. Blocking endogenous GLP-1 receptor action increased endogenous GLP-1 secretion in all groups and increased postprandial glucose, glucagon, and GE in T1D+ and T1D− patients. The insulinogenic index (the ratio of insulin to glucose) decreased in T1D+ patients during blockade of endogenous GLP-1 receptor action.

CONCLUSIONS
Type 1 diabetic patients have normal incretin responses to meals. In type 1 diabetic patients, exogenous GLP-1 decreases peak postprandial glucose by 45% regardless of residual β-cell function. Endogenous GLP-1 regulates postprandial glucose excursions by modulating glucagon levels, GE, and β-cell responsiveness to glucose. Long-term effects of GLP-1 in type 1 diabetic patients should be investigated in future clinical trials.
Improved Insulin Sensitivity by GLUT12 Overexpression in Mice
Authors: Purcell Scott H. , Aerni-Flessner Lauren B. , Willcockson Alexandra R. , Diggs-Andrews Kelly A. , Fisher Simon J. , Moley Kelle H. 
Published: March 2011

OBJECTIVE
Evidence suggests that insulin-sensitive glucose transporters (GLUTs) other than GLUT4 may exist. To investigate whether GLUT12 may represent another insulin-sensitive GLUT, transgenic (TG) mice that overexpress GLUT12 were characterized.

RESEARCH DESIGN AND METHODS
TG mice that overexpressed GLUT12 under a β-actin promoter were generated. Glucose metabolism in TG and wild-type control mice was compared using glucose and insulin tolerance tests and hyperinsulinemic-euglycemic clamps. In addition, basal and insulin-stimulated glucose clearance rates into insulin-sensitive peripheral tissues were measured using [3H]-2-deoxy-d-glucose.

RESULTS
GLUT12 was overexpressed by 40–75% in TG compared with wild-type mice in insulin-sensitive tissues with no change in GLUT4 content. Body weight and fasting blood glucose did not differ between wild-type and TG mice; however, insulin concentrations were reduced in TG mice. Enhanced oral glucose tolerance was noted in TG mice by a reduced blood glucose excursion compared with wild-type mice (P &lt; 0.05). Enhanced insulin sensitivity was noted by a greater decrease in blood glucose in TG mice during insulin tolerance testing. Hyperinsulinemic-euglycemic clamps confirmed enhanced insulin sensitivity in GLUT12-overexpressing mice (P &lt; 0.01). Tissues of TG mice exhibited normal basal glucose clearance rates; however, under insulin-stimulated conditions, glucose clearance was significantly increased (P &lt; 0.01) in tissues of TG mice.

CONCLUSIONS
Increased expression of GLUT12 results in improved whole-body insulin sensitivity mediated by an increased glucose clearance rate in insulin-responsive tissues under insulin-stimulated, but not basal, conditions. These findings provide evidence that GLUT12 represents a novel, second insulin-sensitive GLUT.
Protection From Retinopathy and Other Complications in Patients With Type 1 Diabetes of Extreme Duration
Authors: Sun Jennifer K. , Keenan Hillary A. , Cavallerano Jerry D. , Asztalos Bela F. , Schaefer Ernst J. , Sell David R. , Strauch Christopher M. , Monnier Vincent M. , Doria Alessandro , Aiello Lloyd Paul , King George L. 
Published: March 2011

OBJECTIVE
To assess complication prevalence and identify protective factors in patients with diabetes duration of ≥50 years. Characterization of a complication-free subgroup in this cohort would suggest that some individuals are protected from diabetes complications and allow identification of endogenous protective factors.

RESEARCH DESIGN AND METHODS
Cross-sectional, observational study of 351 U.S. residents who have survived with type 1 diabetes for ≥50 years (Medalists). Retinopathy, nephropathy, neuropathy, and cardiovascular disease were assessed in relation to HbA1c, lipids, and advanced glycation end products (AGEs). Retrospective chart review provided longitudinal ophthalmic data for a subgroup.

RESULTS
A high proportion of Medalists remain free from proliferative diabetic retinopathy (PDR) (42.6%), nephropathy (86.9%), neuropathy (39.4%), or cardiovascular disease (51.5%). Current and longitudinal (the past 15 years) glycemic control were unrelated to complications. Subjects with high plasma carboxyethyl-lysine and pentosidine were 7.2-fold more likely to have any complication. Of Medalists without PDR, 96% with no retinopathy progression over the first 17 years of follow-up did not experience retinopathy worsening thereafter.

CONCLUSIONS
The Medalist population is likely enriched for protective factors against complications. These factors might prove useful to the general population with diabetes if they can be used to induce protection against long-term complications. Specific AGE combinations were strongly associated with complications, indicating a link between AGE formation or processing with development of diabetic vasculopathy.
A Decrease in Glucose Variability Does Not Reduce Cardiovascular Event Rates in Type 2 Diabetic Patients After Acute Myocardial Infarction
Authors: Siegelaar Sarah E. , Kerr Lisa , Jacober Scott J. , Devries J. Hans 
Published: March 2011

OBJECTIVE
To assess the effect of intraday glucose variability (GV) on cardiovascular outcomes in a reanalysis of Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (HEART2D) study data.

RESEARCH DESIGN AND METHODS
Type 2 diabetic patients after acute myocardial infarction were randomized to an insulin treatment strategy targeting postprandial (PRANDIAL; n = 557) or fasting/interprandial (BASAL; n = 558) hyperglycemia. GV was calculated as mean amplitude of glycemic excursions (MAGE), mean absolute glucose (MAG) change, and SD.

RESULTS
The PRANDIAL strategy resulted in an 18% lower MAG than BASAL (mean [SEM] difference 0.09 [0.04] mmol/L/h, P = 0.02). In addition, MAGE and SD were lower in the PRANDIAL group, however, not significantly. HbA1c levels and cardiovascular event rates were comparable between groups.

CONCLUSIONS
A PRANDIAL strategy demonstrated lower intraday GV vs. a BASAL strategy with similar overall glycemic control but did not result in a reduction in cardiovascular outcomes. This does not support the hypothesis that targeting GV would be beneficial in reducing subsequent secondary cardiovascular events.
The characteristics of the chemical flow within the Motru catchment area, south — west Romania
Authors: Ionuş Oana 
Published: March 2011

Abstract
The present paper, with reference to the Motru catchment area, contributes to the hydrochemical studies at an international level and to the completion of the characteristics regarding the chemical flow in Romania. In this regard, it emphasizes once again the dependence between the content of dissolved salts (fixed residue — mg/l) on the one hand and the lithological conditions, human activity, flow and the surface of the catchments on the other hand. The calculation and the analysis of the chemical flow for the Motru catchment area (located in the south-west of Romania) was performed on the basis of two parameters: the average flow of dissolved chemical substances (mg/s) and specific average chemical flow (t/kmp year) recorded at the monitoring stations on the Motru River and its tributaries during the period 2005–2009.
The values obtained (for example: 2.63 mg/s and 47.7 t/km2 year, at the Fata Motrului station, on the Motru River, in 2009) confirm the importance of the areal factors of natural background in the analysis of chemical flow as a morpho-dynamic process and implicitly for the chemical quality of surface waters.
Late Quaternary palaeoenvironment and palaeoclimate of the Lake Fehér (Fehér-tó) sequence at Kardoskút (South Hungary), based on preliminary mollusc records
Authors: Sümegi Pál , Lócskai Tünde , Hupuczi Júlia 
Published: March 2011

Abstract
Forty (22 freshwater gastropod, 14 gastropod, 4 bivalves) species and 3428 specimens of molluscs were collected and identified from a 6.3 m sequence, obtained from a core profile, of lake and fluvial sediments at Kardoskút, South Hungary. According to changes in the molluscan fauna, six malacological-palaeoecological zones can be identified in this profile. The Quaternary malacological data from the Lake Fehér core profile suggests that the Late Pleniglacial and Early Holocene development of the molluscan fauna, and local palaeoclimatic and palaeoenvironmental conditions in this area, differed from other regions in Europe.
Pleistocene trace fossils in the Ironshore Formation, Little Cayman, British West Indies
Authors: Metz Robert 
Published: March 2011

Abstract
Oosparite grainstones of the Pleistocene Ironshore Formation, Little Cayman, British West Indies, contain the trace fossils Conichnus conicus, Ophiomorpha nodosa, and Planolites beverleyensis. The dominance of vertically-oriented trace fossils, complexity of cross-stratifications, coarseness of the sediment channel fill, and presence of several rudstone layers suggest deposition close to the seaward portion of lagoonal channels where higher energy conditions prevailed.
The most problematic variable in the course of human-biometeorological comfort assessment — the mean radiant temperature
Authors: Kántor Noémi , Unger János 
Published: March 2011

Abstract
This paper gives a review on the topic of the mean radiant temperature Tmrt, the most important parameter influencing outdoor thermal comfort during sunny conditions. Tmrt summarizes all short wave and long wave radiation fluxes reaching the human body, which can be very complex (variable in spatial and also in temporal manner) in urban settings. Thermal comfort researchers and urban planners need easy and sound methodological approaches to assess Tmrt. After the basics of the Tmrt calculation some of the methods suitable for obtaining Tmrt also in urban environments will be presented.. Two of the discussed methods are based on instruments which measure the radiation fluxes integral (globe thermometer, pyranometer-pyrgeometer combination), and three of the methods are based on modelling the radiation environment with PC software (RayMan, ENVI-met and SOLWEIG).
State of stress in the northern Tabas block, east-central Iran, as inferred from focal mechanisms of the 1978 Tabas earthquake sequence
Authors: Behzad Zamani G. 
Published: March 2011

Abstract
In this paper, the state of stress in the northern Tabas block in east-central Iran is analyzed based on the systematic inversion of aftershock focal mechanisms from the 1978.09.16 Tabas earthquake, to characterise the stress regime that controls most earthquakes in this area. Here, stress inversions of double-couple focal mechanisms of earthquakes recorded during the 30 days following the main shock have been carried out. The calculated average stress regime indicates dominant major 226° to 237° trending compression for the Tabas region. The dominating regime in east-central Iran is thrusting with a minimum stress axis, σ
3, close to vertical. The reconstruction of the main seismotectonic stress in east-central Iran with a NE-SW compression is consistent with independent information of the active plate convergence related to Arabia-Eurasia convergence. Most earthquakes in the mentioned area occur near or around concealed Quaternary thrust faults with their activity being controlled by the NE-SW compression. Where ϕ, the ratio of principal stress differences, is 0.5, a small difference between σ
2; σ
3 and σ
1 and small amounts of deviatoric stress is indicated. Therefore, for small deviatoric horizontal σ
1 it is not possible to increase and reactivate small sections of basement thrust faults and create secondary basement aftershocks. Reconstructed stress regimes in this study for sedimentary cover (237) and basement (226) of Tabas are similar. Therefore, it seems that the basement and cover were coupled together, possibly along the 2–4 km of upper Precambrian low-grade metamorphic rocks. Then these segments of the fold-and-thrust belt were involved in similar seismic activity under a similar stress regime.
Territorial dynamics and boundary effects in a protected area of the Central Iberian Peninsula
Authors: Heras Paloma , Fernández-Sañudo Paloma , López-Estébanez Nieves , Roldán María 
Published: March 2011

Abstract
We analysed the main changes in land use over a 21 year period within the perimeter of a Protected Natural Area (PNA) and outside this perimeter. The area is characterised by its Mediterranean mid-mountain landscape and its piedmont, which extends almost as far as the city of Madrid. We employed cartography of land use and plant formation from 1980 and 2001. We identified land uses and their changes in this time period in order to determine the principal territorial dynamics (scrub encroachment, urban development, forest encroachment, new pastures and new crops). Subsequently, we performed a comparative analysis between the changes inside and those outside the protected area. The results show that there is a boundary effect between the protected area and the surrounding zone, which is more notable in the areas where urban development has intensified. This kind of research serves to establish whether or not a PNA contributes to protecting and conserving natural resources as compared to what occurs in the unprotected surrounding area, which tends to be subjected to more aggressive dynamics.
Effect of block rotation on the pitch of slickenlines
Authors: Xu Shunshan , Nieto-Samaniego Ángel , Alaniz-Álvarez Susana , Velasquillo-Martínez Luis 
Published: March 2011

Abstract
Rotation of faults or pre-existing weakness planes produce two effects on the slickenlines of fault planes. First, the rotation leads to changes in the pitch of slickenlines. As a result, the aspect of the pre-existing fault may change. For example, after rotation, a normal fault may show features of an oblique fault, a strike-slip fault, or a thrust fault. Second, due to rotation, stress states on the fault planes are different from those before the rotation. As a consequence some previous planes may be reactivated. For an isolated plane, the reactivation due to rotation can produce new sets of slickenlines. With block rotation, superimposed slickenlines can be generated in the same tectonic phase. Thus, it is not appropriate to use fault-slip data from slickenlines to analyze the stress tensor in a region where there is evidence of block rotation. As an example, we present the data of slickenlines from core samples in the Tunich area of the Gulf of Mexico. The results wrongly indicate that the calculated stress tensor deviates from the far-field stress tensor.