bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D Supplementation in Chronic Kidney Disease
Authors: Kandula Praveen , Dobre Mirela , Schold Jesse D. , Schreiber Martin J. , Mehrotra Rajnish , Navaneethan Sankar D. 
Published: September 2010

Summary

Background and objectives
Vitamin D deficiency is highly prevalent among patients with chronic kidney disease (CKD). The benefits and harms of vitamin D supplementation (ergocalciferol or cholecalciferol) were assessed in patients with nondialysis-dependent CKD, dialysis-dependent CKD, and renal transplant recipients.

Design, setting, participants, & measurements
MEDLINE (1966 to September 2009), SCOPUS (September 2009), and nephrology conference proceedings were searched for relevant observational and randomized controlled trials (RCTs). Treatment effects were summarized as mean differences (MDs) with 95% confidence intervals (CIs) using a random effects model. Separate analyses were conducted for observational studies and RCTs.

Results
Twenty-two studies (17 observational and 5 RCTs) were included. There was a significant improvement in 25-hydroxyvitamin D (MD 24.1 ng/ml, 95% CI 19.6 to 28.6) and an associated decline in parathyroid hormone (PTH) levels (MD −41.7 pg/ml, 95% CI −55.8 to −27.7) among observational studies. PTH reduction was higher in dialysis patients. Among RCTs, there was a significant improvement in 25-hydroxyvitamin D (MD 14 ng/ml, 95% CI 5.6 to 22.4) and an associated decline in PTH levels (MD −31.5 pg/ml, 95% CI −57 to −6.1). A low incidence of hypercalcemia and hyperphosphatemia was reported with vitamin D supplementation. Cardiovascular and skeletal effects of vitamin D supplementation have not been studied. Included studies were mostly of low to moderate quality.

Conclusions
Available evidence from low-to-moderate quality observational studies and fewer RCTs suggests that vitamin D supplementation improves biochemical endpoints. However, whether such improvements translate into clinically significant outcomes is yet to be determined.
Water Prescription in Autosomal Dominant Polycystic Kidney Disease
Authors: Wang Connie J. , Creed Catherine , Winklhofer Franz T. , Grantham Jared J. 
Published: September 2010

Summary

Background and objectives
In animal models of polycystic kidney disease, the ingestion of large amounts of water promotes diuresis by suppressing plasma levels of arginine vasopressin (AVP) and renal levels of cAMP, slowing cyst progression. Whether simple water ingestion is a potential therapeutic strategy for individuals with autosomal dominant polycystic kidney disease (ADPKD) is unknown. In this study, a simple method to quantify the amount of water to achieve a specific mean urine osmolality target in patients with ADPKD was developed and tested.

Design, setting, participants, & measurements
In eight ADPKD patients eating typical diets, osmolality and volume were measured in 24-hour urine collections. The amount of additional ingested water required daily to achieve a mean urine osmolality of 285 ± 45 mosm/kg was determined. Participants were instructed to distribute the prescribed water over waking hours for each of 5 days. Blood chemistries, 24-hour urine collections, BP, and weight were measured before and after the period of supplemental water intake.

Results
Five patients achieved the 285 mosm/kg urine target without difficulty. Mean urine osmolality decreased and mean urine volume increased; serum sodium, weight, and BP were unchanged. Daily osmolar excretion remained constant, indicating a stable ad lib dietary intake of solutes and protein over the 2-week study period.

Conclusions
The amount of additional water needed to achieve a urine osmolality target can be approximated from the urine osmolar excretion in ADPKD patients eating typical diets, providing a quantitative method to prescribe supplemental water for such individuals.
Serum Iron Markers Are Inadequate for Guiding Iron Repletion in Chronic Kidney Disease
Authors: Ferrari Paolo , Kulkarni Hemant , Dheda Shyam , Betti Susanne , Harrison Colin , St. Pierre Timothy G. , Olynyk John K. 
Published: September 2010

Summary

Background and objectives
Iron (Fe) overload may complicate parenteral Fe therapy used to enhance the efficacy of erythropoietic-stimulating agents in the treatment of anemia of chronic kidney disease. However, serum Fe markers are influenced by inflammation or malignancy and may not accurately reflect the amount of body Fe.

Design, setting, participants, & measurements
We studied the relationship between parenteral Fe therapy, conventional serum Fe markers, and liver iron concentration (LIC) measured using magnetic resonance R2 relaxometry (FerriScan) in 25 Fe-deficient predialysis chronic kidney disease patients before and 2 and 12 weeks after single high-dose intravenous Fe and in 15 chronic hemodialysis patients with elevated serum ferritin (>500 μg/L).

Results
In predialysis patients, there was strong dose dependency between the administered Fe dose and changes in LIC at weeks 2 and 12; however, no dose dependency between Fe dose and changes in ferritin or transferrin saturation (TSAT) were observed. In hemodialysis patients, LIC correlated with the cumulative Fe dose and duration of dialysis but not with current ferritin or TSAT. The cumulative Fe dose remained a significant independent predictor of LIC in a multiple regression model. Two dialysis patients who received >6 g parenteral Fe had substantially elevated LIC >130 μmol/g, which is associated with hemochromatosis.

Conclusions
In Fe-deficient predialysis patients, intravenous Fe therapy is associated with increases in LIC unrelated to changes in conventional Fe markers. In hemodialysis patients, TSAT and ferritin are poor indicators of body Fe load, and some patients have LICs similar to those found in hemochromatosis.
Circulating Endotoxemia
Authors: McIntyre Christopher W. , Harrison Laura E.A. , Eldehni M. Tarek , Jefferies Helen J. , Szeto Cheuk-Chun , John Stephen G. , Sigrist Mhairi K. , Burton James O. , Hothi Daljit , Korsheed Shvan , Owen Paul J. , Lai Ka-Bik , Li Philip K.T. 
Published: September 2010

Summary

Background and objectives
Translocated endotoxin derived from intestinal bacteria has a wide range of adverse effects on cardiovascular (CV) structure and function, driving systemic inflammation, atherosclerosis and oxidative stress. This study's aim was to investigate endotoxemia across the spectrum of chronic kidney disease (CKD).

Design, setting, participants, & measurements
Circulating endotoxin was measured in 249 patients comprising CKD stage 3 to 5 and a comparator cohort of hypertensive patients without significant renal impairment. Patients underwent extended CV assessment, including pulse wave velocity and vascular calcification. Hemodialysis (HD) patients also received detailed echocardiographic-based intradialytic assessments. Patients were followed up for 1 year to assess survival.

Results
Circulating endotoxemia was most notable in those with the highest CV disease burden (increasing with CKD stage), and a sharp increase was observed after initiation of HD. In HD patients, predialysis endotoxin correlated with dialysis-induced hemodynamic stress (ultrafiltration volume, relative hypotension), myocardial stunning, serum cardiac troponin T, and high-sensitivity C-reactive protein. Endotoxemia was associated with risk of mortality.

Conclusions
CKD patients are characteristically exposed to significant endotoxemia. In particular, HD-induced systemic circulatory stress and recurrent regional ischemia may lead to increased endotoxin translocation from the gut. Resultant endotoxemia is associated with systemic inflammation, markers of malnutrition, cardiac injury, and reduced survival. This represents a crucial missing link in understanding the pathophysiology of the grossly elevated CV disease risk in CKD patients, highlighting the potential toxicity of conventional HD and providing a novel set of potential therapeutic strategies to reduce CV mortality in CKD patients.
Effects of Salsalate Therapy on Recovery From Vascular Injury in Female Zucker Fatty Rats
Authors: Murthy Subramanyam N. , Desouza Cyrus V. , Bost Neal W. , Hilaire Rose-Claire St. , Casey David B. , Badejo Adeleke M. , Dhaliwal Jasdeep S. , McGee Jennifer , McNamara Dennis B. , Kadowitz Philip J. , Fonseca Vivian A. 
Published: September 2010

OBJECTIVESalsalate is a dimeric form of salicylic acid that has been shown to have anti-inflammatory activity and to reduce glucose levels, insulin resistance, and cytokine expression. However, the effect of salsalate on vascular injury has not been determined. The objective of this study is to investigate the effect of salsalate on vascular injury and repair in a rat model of carotid artery balloon catheter injury.RESEARCH DESIGN AND METHODSSalsalate treatment was started in female Zucker fatty rats (insulin resistant) 1 week before carotid artery balloon catheter injury and continued for 21 days, at which time the animals were killed and studied.RESULTSTreatment with salsalate significantly decreased the intima-to-media ratio and upregulated the expression of aortic endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (ser 1177), and manganese superoxide dismutase (MnSOD) and reduced serum interleukin (IL)-6 with concomitant downregulation of nuclear factor (NF) κB subunit p65 and vascular endothelial growth factor (VEGF) expression in the balloon-injured carotid artery of female Zucker fatty rats.CONCLUSIONSThe present study shows that salsalate treatment decreases vascular damage caused by balloon catheter injury in female Zucker fatty rats. The beneficial effect of salsalate on vascular injury was associated with upregulation of eNOS, p-eNOS, and MnSOD, which reduce oxidative stress and have anti-inflammatory properties, as evidenced by reduction in serum IL-6 and the downregulation of VEGF and NFκB, which promote inflammation without changing glucose levels. These results suggest that salsalate may be useful in reducing vascular injury and restenosis following interventional revascularization procedures.
Disruption of Hepatic Leptin Signaling Protects Mice From Age- and Diet-Related Glucose Intolerance
Authors: Huynh Frank K. , Levi Jasna , Denroche Heather C. , Gray Sarah L. , Voshol Peter J. , Neumann Ursula H. , Speck Madeleine , Chua Streamson C. , Covey Scott D. , Kieffer Timothy J. 
Published: September 2010

OBJECTIVE
The liver plays a critical role in integrating and controlling glucose metabolism. Thus, it is important that the liver receive and react to signals from other tissues regarding the nutrient status of the body. Leptin, which is produced and secreted from adipose tissue, is a hormone that relays information regarding the status of adipose depots to other parts of the body. Leptin has a profound influence on glucose metabolism, so we sought to determine if leptin may exert this effect in part through the liver.

RESEARCH DESIGN AND METHODS
To explore this possibility, we created mice that have disrupted hepatic leptin signaling using a Cre-lox approach and then investigated aspects of glucose metabolism in these animals.

RESULTS
The loss of hepatic leptin signaling did not alter body weight, body composition, or blood glucose levels in the mild fasting or random-fed state. However, mice with ablated hepatic leptin signaling had increased lipid accumulation in the liver. Further, as male mice aged or were fed a high-fat diet, the loss of hepatic leptin signaling protected the mice from glucose intolerance. Moreover, the mice displayed increased liver insulin sensitivity and a trend toward enhanced glucose-stimulated plasma insulin levels. Consistent with increased insulin sensitivity, mice with ablated hepatic leptin signaling had increased insulin-stimulated phosphorylation of Akt in the liver.

CONCLUSIONS
These data reveal that unlike a complete deficiency of leptin action, which results in impaired glucose homeostasis, disruption of leptin action in the liver alone increases hepatic insulin sensitivity and protects against age- and diet-related glucose intolerance. Thus, leptin appears to act as a negative regulator of insulin action in the liver.
Enhanced Energy Expenditure, Glucose Utilization, and Insulin Sensitivity in VAMP8 Null Mice
Authors: Zong Haihong , Wang Cheng-Chun , Vaitheesvaran Bhavapriya , Kurland Irwin J. , Hong Wanjin , Pessin Jeffrey E. 
Published: September 2010

OBJECTIVE
Previous studies have demonstrated that the VAMP8 protein plays a complex role in the control of granule secretion, transport vesicle trafficking, phagocytosis, and endocytosis. The present study was aimed to investigate the role of VAMP8 in mediating GLUT4 trafficking and therefore insulin action in mice.

RESEARCH DESIGN AND METHODS
Physiological parameters were measured using Oxymax indirect calorimetry system in 12-week-old VAMP8 null mice. Dynamic analysis of glucose homeostasis was assessed using euglycemic–hyperinsulinemic clamp coupled with tracer radioactively labeled 2-deoxyglucose. Insulin stimulated GLUT4 protein expressions on muscle cell surface were examined by immunofluorescence microscopy.

RESULTS
VAMP8 null mice display reduced adiposity with increased energy expenditure despite normal food intake and reduced spontaneous locomotor activity. In parallel, the VAMP8 null mice also had fasting hypoglycemia (84 ± 11 vs. 115 ± 4) and enhanced glucose tolerance with increased insulin sensitivity due to increases in both basal and insulin-stimulated glucose uptake in skeletal muscle (0.19 ± 0.04 vs. 0.09 ± 0.01 mmol/kg/min during basal, 0.6 ± 0.04 vs. 0.31 ± 0.06 mmol/kg/min during clamp in red-gastrocnemius muscle, P &lt; 0.05). Consistent with a role for VAMP8 in the endocytosis of the insulin-responsive GLUT4, sarcolemma GLUT4 protein levels were increased in both the basal and insulin-stimulated states without any significant change in the total amount of GLUT4 protein or related facilitative glucose transporters present in skeletal muscle, GLUT1, GLUT3, and GLUT11.

CONCLUSIONS
These data demonstrate that, in the absence of VAMP8, the relative subcellular distribution of GLUT4 is altered, resulting in increased sarcolemma levels that can account for increased glucose clearance and insulin sensitivity.
Both Polymorphic Variable Number of Tandem Repeats and Autoimmune Regulator Modulate Differential Expression of Insulin in Human Thymic Epithelial Cells
Authors: Cai Chuan Qi , Zhang Tao , Breslin Mary B. , Giraud Matthieu , Lan Michael S. 
Published: September 2010

OBJECTIVE
Polymorphic INS-VNTR plays an important role in regulating insulin transcript expression in the human thymus that leads to either insulin autoimmunity or tolerance. The molecular mechanisms underlying the INS-VNTR haplotype-dependent insulin expression are still unclear. In this study, we determined the mechanistic components underlying the differential insulin gene expression in human thymic epithelial cells, which should have profound effects on the insulin autoimmune tolerance induction.

RESEARCH DESIGN AND METHODS
A repetitive DNA region designated as a variable number of tandem repeats (VNTR) is located upstream of the human insulin gene and correlates with the incidence of type 1 diabetes. We generated six class I and two class III VNTR constructs linked to the human insulin basal promoter or SV40 heterologous promoter/enhancer and demonstrated that AIRE protein modulates the insulin promoter activities differentially through binding to the VNTR region.

RESULTS
Here we show that in the presence of the autoimmune regulator (AIRE), the class III VNTR haplotype is responsible for an average of three-fold higher insulin expression than class I VNTR in thymic epithelial cells. In a protein-DNA pull-down experiment, AIRE protein is capable of binding to VNTR class I and III probes. Further, the transcriptional activation of the INS-VNTR by AIRE requires the insulin basal promoter. The VNTR sequence loses its activation activity when linked to a heterologous promoter and/or enhancer.

CONCLUSIONS
These findings demonstrate a type 1 diabetes predisposition encoded by the INS-VNTR locus and a critical function played by AIRE, which constitute a dual control mechanisms regulating quantitative expression of insulin in human thymic epithelial cells.
First-Trimester Prediction of Gestational Diabetes Mellitus: Examining the Potential of Combining Maternal Characteristics and Laboratory Measures
Authors: Savvidou Makrina , Nelson Scott M. , Makgoba Mahlatse , Messow Claudia-Martina , Sattar Naveed , Nicolaides Kypros 
Published: September 2010

OBJECTIVE
Predictors of gestational diabetes mellitus (GDM) have been widely studied, but few studies have considered multiple measures. Our objective was to integrate several potential GDM predictors with consideration to both simple and novel measures and to determine the extent to which GDM can be predicted in the first trimester.

RESEARCH DESIGN AND METHODS
We identified first-trimester maternal samples from 124 women who developed GDM and 248 control subjects who did not. We gathered data on age, BMI, parity, race, smoking, prior GDM, family history of diabetes, and blood pressure. Using retrieved samples, we measured routine (lipids, high-sensitivity C-reactive protein, and γ-glutamyltransferase) and novel (adiponectin, E-selectin, and tissue plasminogen activator [t-PA]) parameters. We determined independent predictors from stepwise regression analyses, calculated areas under the receiver-operating characteristic curves (AUC-ROC), and integrated discrimination improvement (IDI) for relevant models.

RESULTS
Compared with control subjects, women who subsequently developed GDM were older, had higher BMIs, were more likely to be of Asian origin, had a history of GDM or family history of type 2 diabetes, and had higher systolic blood pressure (P &lt; 0.05 for all). With regard biochemical measures, stepwise analyses identified only elevated t-PA and low HDL cholesterol levels as significant (P ≤ 0.015) independent predictors of GDM beyond simple non–laboratory-based maternal measures. Their inclusion improved the AUC-ROC from 0.824 to 0.861 and IDI by 0.052 (0.017–0.115).

CONCLUSIONS
GDM can be usefully estimated from a mix of simple questions with potential for further improvement by specific blood measures (lipids and t-PA).
Diminished Superoxide Generation Is Associated With Respiratory Chain Dysfunction and Changes in the Mitochondrial Proteome of Sensory Neurons From Diabetic Rats
Authors: Akude Eli , Zherebitskaya Elena , Chowdhury Subir K. Roy , Smith Darrell R. , Dobrowsky Rick T. , Fernyhough Paul 
Published: September 2010

OBJECTIVE
Impairments in mitochondrial function have been proposed to play a role in the etiology of diabetic sensory neuropathy. We tested the hypothesis that mitochondrial dysfunction in axons of sensory neurons in type 1 diabetes is due to abnormal activity of the respiratory chain and an altered mitochondrial proteome.

RESEARCH DESIGN AND METHODS
Proteomic analysis using stable isotope labeling with amino acids in cell culture (SILAC) determined expression of proteins in mitochondria from dorsal root ganglia (DRG) of control, 22-week-old streptozotocin (STZ)-diabetic rats, and diabetic rats treated with insulin. Rates of oxygen consumption and complex activities in mitochondria from DRG were measured. Fluorescence imaging of axons of cultured sensory neurons determined the effect of diabetes on mitochondrial polarization status, oxidative stress, and mitochondrial matrix-specific reactive oxygen species (ROS).

RESULTS
Proteins associated with mitochondrial dysfunction, oxidative phosphorylation, ubiquinone biosynthesis, and the citric acid cycle were downregulated in diabetic samples. For example, cytochrome c oxidase subunit IV (COX IV; a complex IV protein) and NADH dehydrogenase Fe-S protein 3 (NDUFS3; a complex I protein) were reduced by 29 and 36% (P &lt; 0.05), respectively, in diabetes and confirmed previous Western blot studies. Respiration and mitochondrial complex activity was significantly decreased by 15 to 32% compared with control. The axons of diabetic neurons exhibited oxidative stress and depolarized mitochondria, an aberrant adaption to oligomycin-induced mitochondrial membrane hyperpolarization, but reduced levels of intramitochondrial superoxide compared with control.

CONCLUSIONS
Abnormal mitochondrial function correlated with a downregulation of mitochondrial proteins, with components of the respiratory chain targeted in lumbar DRG in diabetes. The reduced activity of the respiratory chain was associated with diminished superoxide generation within the mitochondrial matrix and did not contribute to oxidative stress in axons of diabetic neurons. Alternative pathways involving polyol pathway activity appear to contribute to raised ROS in axons of diabetic neurons under high glucose concentration.
Le blog d'adolescent : à la frontière de soi, du réel et du virtuel
Authors: Nicaise Emmanuel , Lefebvre Alex 
Published: September 2010

Résumé Plus d’un quart des adolescents belges posséderaient un blog. À l’aide d’une étude psychosociale par questionnaire et entretiens, nous avons tenté de cerner les différentes fonctions que ces blogs peuvent avoir pour ces adolescents. Bien au-delà du simple partage d’information, le blog semble être un nouveau lieu de culture, d’échange et de présentation de soi. L’analogie prégnante du blog et de la peau, nous fait situer l’objet à la frontière du soi, du virtuel et du réel ; l’adolescent l’utilisant pour se présenter aux autres tout en se protégeant, amenant dans le « virtuel » des extraits de sa réalité quotidienne qu’il peut choisir, manipuler et rappeler, contrôlant ainsi son image virtuelle qui vient inévitablement se superposer à son image réelle. L’adolescent peut ainsi utiliser le blog comme une nouvelle forme d’espace de transition.
Characteristics of Ponds Used by Breeding Mottled Ducks on the Chenier Plain of the Texas Gulf Coast
Authors: Haukos David , Martinez Stephanie , Heltzel Jeannie 
Published: September 2010

Abstract
Mottled ducks Anas fulvigula are nonmigratory and primarily depend on habitats associated with coastal marshes of the Gulf Coast for their entire life cycle. Much of remaining available coastal marsh habitats of the Texas Gulf Coast are managed by state and federal agencies. The Texas Gulf Coast breeding population of mottled ducks has recently declined dramatically. To aid in development of management plans for breeding mottled ducks, we estimated the number of potential pair ponds available on the Texas Chenier Plain National Wildlife Refuge Complex relative to marsh type (fresh, intermediate, brackish, and saline), estimated occupancy, compared habitats of used and unused pair ponds, and evaluated pair pond selection relative to marsh type during spring 2004 and 2005. Greater than 18,000 ponds were recorded in &gt;22,400 ha of coastal marsh with &gt;74% of potential pair ponds in the intermediate marsh type. Average pond size of 425 randomly selected ponds across marsh types was 0.09 ha. Pond occupancy was estimated as 1.3% and 2.5% in 2004 and 2005, respectively, in 634 ponds surveyed for presence of mottled duck pairs. Mottled ducks selected for ponds in fresh marsh with short surrounding vegetation associated with recent cattle grazing, but avoided recently (&lt;3 mo prior) burned areas. Pond area was greater with shallower water depth for used compared to unused ponds. The presence and coverage of submergent and emergent vegetation did not influence use of pair ponds by mottled ducks. Development of breeding habitat (pair ponds, nesting cover, brood habitat) in fresh marsh will benefit mottled ducks. Our results indicate development of breeding habitat on the Texas Gulf Coast, and vegetation management using cattle grazing timed for disturbance in fresh marsh during mid- to late winter and early spring will further attract breeding mottled ducks.