bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between plasma osteoprotegerin concentrations and urinary albumin excretion in Type 2 diabetes
Authors: Xiang G. D. , Pu J. H. , Zhao L. S. , Sun H. L. , Hou J. , Yue L. 
Published: February 2009

AbstractAims  Osteoprotegerin (OPG) is a recently identified inhibitor of bone resorption. Recent studies indicate that OPG is also associated with endothelial dysfunction in Type 2 diabetes. The aim was to investigate the relationship between plasma OPG levels and urinary albumin excretion (UAE) in Type 2 diabetic patients.Methods  This study included 154 newly diagnosed Type 2 diabetic patients and 46 healthy subjects. Plasma OPG and 24‐h UAE were measured. High‐resolution ultrasound was used to measure flow‐mediated (endothelium‐dependent arterial) dilation (FMD).Results  Compared with the normoalbuminuric subgroup, OPG levels in the microalbuminuric subgroup were significantly higher, and OPG levels in macroalbuminuria subgroup were significantly higher than those in the normoalbuminuria and albuminuria subgroups. Multiple regression analysis showed that only FMD (r = −0.26), C‐reactive protein (r = 0.23), fasting blood glucose (r = 0.25), 2‐h blood glucose (r = 0.21), HbA1c (r = 0.28), UAE (r = 0.27) and retinopathy (r = 0.27) were significant factors associated with OPG. Pearson’s correlation analyses showed a positive correlation between OPG and logUAE (r = 0.440) and negative correlations between OPG and FMD (r = −0.284), and between FMD and logUAE (r = −0.602).Conclusions  Plasma OPG levels are significantly associated with UAE in Type 2 diabetic patients.
Decreasing concentration of interstitial glucose in REM sleep in subjects with normal glucose tolerance
Authors: Bialasiewicz P. , Pawlowski M. , Nowak D. , Loba J. , Czupryniak L. 
Published: February 2009

AbstractAims  Sleep is divided into two major stages, non‐rapid eye movement (NREM) and rapid eye movement (REM), which are distinct in various neuroendocrine respects. NREM/REM cycles influence insulin and glucagon secretion; however, glucose concentrations in REM compared with NREM have not been directly explored. The aim was to investigate the differences in glucose concentrations in interstitial fluid (IGC) between NREM/REM cycles using a continuous glucose monitoring system (CGMS).Methods  Thirteen subjects were eligible for analysis out of the 28 enrolled. All underwent standard polysomnography for the assessment of sleep stages and the exclusion of sleep apnoea syndrome with CGMS and subsequent morning oral glucose tolerance test (exclusion of glucose intolerance or diabetes).Results  The IGC in REM fell in 12 out of the 13 subjects, whereas the IGC in NREM increased in eight out of the 13 subjects. Therefore, the mean change of IGC differed in direction between sleep stages: −0.028 (−0.045 to −0.011) for REM vs. 0.005 (−0.012 to 0.017) for NREM [median (QR), P = 0.007, n = 13], with the mean difference of 0.038 mmol/l × 5 min−1 (95% confidence interval 0.012, 0.064). The mean glucose concentration in REM sleep was lower than in NREM: 4.29 ± 1.00 vs. 4.53 ± 0.90 mmol/l (mean ± sd, P = 0.003, n = 13).Conclusions  The decrease in IGC in REM compared with NREM sleep, with lower absolute values, may arise from different physiological events observed in these sleep stages. The REM‐related decline in glucose concentrations may be a risk factor for nighttime hypoglycaemia.
Factors determining normalization of glucose intolerance in middle‐aged Swedish men and women: a 8–10‐year follow‐up
Authors: Alvarsson M. , Hilding A. , Östenson C.‐G. 
Published: February 2009

AbstractAims  To examine factors in middle‐aged Swedish men and women predicting the conversion from a state of abnormal glucose regulation to normal glucose tolerance (NGT) after 8–10 years.Methods  At baseline 3128 men and 4821 women, aged 35–56 years, without previously diagnosed diabetes underwent an oral glucose tolerance test and completed a questionnaire. At follow‐up, 2383 men and 3329 women were re‐examined. The study group consisted of 156 men and 124 women with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both at baseline.Results  The rate of reversal to NGT from IFG or IGT was similar regardless of gender. In participants having IFG or IGT, reversal to NGT was predicted by low fasting and 2‐h insulin, homeostasis model assessment of insulin resistance and of pancreatic β cell function, body mass index and waist circumference without differences between gender and baseline glucose tolerance group. Low 2‐h glucose, however, predicted reversal to NGT in men with IFG at baseline, but not in men with IGT at baseline, or in women with either IFG or IGT at baseline. Men reverting to NGT had higher coffee consumption and women had higher baseline leisure‐time physical activity. In multiple logistic regression, including all participants, low fasting and 2‐h glucose remained independent predictors of reverting to NGT.Conclusions  Factors predicting reversal to NGT were measures correlated with low insulin resistance, but also lower insulin secretion, perhaps indicating a lower pancreatic β cell workload in those who reverted. In men, but not in women, low 2‐h glucose was of predictive value.
Metabolic syndrome and short‐term heart rate variability in young adults
Authors: Koskinen T. , Kähönen M. , Jula A. , Mattsson N. , Laitinen T. , Keltikangas‐Järvinen L. , Viikari J. , Välimäki I. , Rönnemaa T. , Raitakari O. T. 
Published: February 2009

AbstractAims  Heart rate variability (HRV) can be used to estimate autonomic nervous control of the cardiovascular system. In middle‐aged subjects, the metabolic syndrome (MetS) is associated with lower HRV. We hypothesized that alterations in autonomic balance are already present in young adults with the MetS, and analysed the association of short‐term HRV with the MetS (using the National Cholesterol Education Program definition), in 1889 subjects aged 24–39 years.Methods  Short‐term (3 min) HRV analysis included high‐frequency (HF), low‐frequency (LF) and total (TP) spectral components of HRV and LF/HF ratio.Results  The presence of the MetS was associated with lower HF, LF and TP in men and women, and with higher LF/HF ratio in women. In men, waist circumference was the strongest individual MetS component that associated with HRV. After adjustments for age and heart rate, MetS was associated with lower HF and higher LF/HF ratio in women, but only with a lower TP in men (all P < 0.05).Conclusions  MetS is associated with lower HRV in young adults. The individual components of MetS are differentially associated with HRV in men and in women. Our results are consistent with lower vagal activity and a possible increase in sympathetic predominance in women with the MetS. This sex difference in vagal activity and sympathovagal balance may partly explain the greater increase in cardiovascular risk associated with MetS in women than in men.
The prevalence of Type 2 diabetes and its associated health problems in a community‐dwelling elderly population
Authors: Hewitt J. , Smeeth L. , Bulpitt C. J. , Fletcher A. E. 
Published: February 2009

AbstractAims  Prevalence estimates of Type 2 diabetes and its associated health problems in elderly populations are rare, especially in the very elderly.Methods  A sample of 15 095 community‐dwelling older people aged ≥ 75 years were assessed. Type 2 diabetes and associated health problems were identified using self‐reporting, general practitioner records, drug histories, and blood and urine measurements.Results  There were 1177 people identified as having Type 2 diabetes mellitus, giving an overall prevalence of 7.8% (95% confidence interval 7.1, 8.5), 9.4% (8.4, 10.5) for men and 6.8% (6.1, 7.6) for women. The age, sex and smoking adjusted odds ratios for various health problems, comparing people with and without diabetes were: low vision 1.6 (1.3, 1.9), proteinuria 1.7 (1.4, 2.1), chronic kidney disease stage 4 or 5 1.5 (1.0, 2.1), angina 1.3 (1.1, 1.6), myocardial infarction 1.5 (1.2, 1.8), cerebrovascular event 2.0 (1.8, 2.1) and foot ulceration 1.7 (1.2, 2.4).Conclusions  The prevalence of Type 2 diabetes is not high in community‐dwelling older people, but diabetes was a contributory factor to a number of health problems.
Predictors of future fasting and 2‐h post‐OGTT plasma glucose levels in middle‐aged men and women—the Inter99 study
Authors: Færch K. , Vaag A. , Witte D. R. , Jørgensen T. , Pedersen O. , Borch‐Johnsen K. 
Published: February 2009

AbstractAims  Screening and prevention strategies for Type 2 diabetes require insight into the aetiological and potentially different risk factors leading to early impairments of fasting plasma glucose (FPG) and 2‐h post‐load plasma glucose (2hPG) levels. We studied whether risk factors predicting subtle elevations of FPG levels were different from those predicting elevations of 2hPG levels in men and women.Methods  We used baseline and 5‐year follow‐up data from middle‐aged men and women with normal glucose tolerance (NGT) at baseline in the Danish population‐based Inter99 study (n = 3164). Anthropometric and non‐anthropometric baseline predictors of the 5‐year FPG and 2hPG levels were estimated in linear regression models stratified by gender.Results  In men, but not in women, smoking and family history of diabetes predicted increased FPG levels, whereas high physical activity predicted a decline in 2hPG levels. Among the anthropometric variables, large waist circumference was the strongest predictor of increased FPG levels in men, whereas high body mass index (BMI) was the strongest predictor of increased FPG levels in women. In both men and women, BMI and waist circumference were equally strong in predicting 2hPG levels. Furthermore, short height predicted increased 2hPG levels in men, and short height and low hip circumference predicted increased 2hPG levels in women.Conclusions  Risk factors that predict future FPG levels are different from those predicting future 2hPG levels. Furthermore, different risk factors predict glycaemic levels in men compared with women. These findings indicate that different aetiological pathways may lead to Type 2 diabetes in men and women.
Altered respiratory function is associated with increased metabolic risk, independently of adiposity, fitness and physical activity
Authors: Steele R. M. , Finucane F. M. , Simmons R. K. , Griffin S. J. , Wareham N. J. , Ekelund U. ,   On behalf of the ProActive research team
Published: February 2009

AbstractAims  Reduced lung function is associated with an adverse metabolic risk profile, even after adjusting for body fatness. However, previous observations may have been confounded by aerobic fitness and physical activity. This study aimed to examine the association between lung function and both metabolic risk and insulin resistance in a cohort of White British adults with a family history of Type 2 diabetes, and to explore the extent to which these associations are independent of body fatness, aerobic fitness (VO2max) and objectively measured physical activity.Methods  Adults (n = 320, mean age 40.4 ± 6.0 years) underwent measurement of physical activity energy expenditure (PAEE), spirometry [forced expiratory volume in 1 s (FEV1)] and forced vital capacity (FVC), aerobic fitness (predicted VO2max), and anthropometric and metabolic status at baseline and again after 1 year (n = 257) in the ProActive trial. Clustered metabolic risk was calculated by summing standardized values for triglycerides, fasting insulin, fasting glucose, blood pressure and the inverse of high‐density lipoprotein‐cholesterol. A cross‐sectional analysis using linear regression with repeated measures was performed.Results  Both FEV1 and FVC were inversely and statistically significantly associated with metabolic risk and insulin resistance after adjusting for age, sex, smoking status, height, PAEE and fitness. The associations with metabolic risk remained significant after adjusting for measures of body fatness, but those with insulin resistance did not.Conclusions  Reduced lung function was associated with increased metabolic risk in this cohort of carefully characterized at‐risk individuals. This association was independent of overall and central body fatness, objectively measured physical activity and aerobic fitness.
Population genetic structure of rock ptarmigan in the ‘sky islands’ of French Pyrenees: implications for conservation
Authors: Bech N. , Boissier J. , Drovetski S. , Novoa C. 
Published: February 2009

AbstractExpected consequences of global warming include habitat reduction in many cool climate species. Rock ptarmigan is a Holarctic grouse that inhabits arctic and alpine tundra. In Europe, the Pyrenean ptarmigan inhabits the southern edge of the species' range and since the last glacial maximum its habitat has been severely fragmented and is restricted to high‐alpine zones or ‘sky islands’. A recent study of rock ptarmigan population genetic in Europe found that the Pyrenean ptarmigan had very low genetic diversity compared with that found in the Alps and Scandinavia. Habitat fragmentation and reduced genetic diversity raises concerns about the viability of ptarmigan populations in the Pyrenees. However, information on population structuring and gene flow across the Pyrenees, which is essential for designing a sound management plan, is absent. In this study, we use seven microsatellites and mitochondrial control region sequences to investigate genetic variation and differentiation among five localities across the Pyrenees. Our analyses reveal the presence of genetic differentiation among all five localities and a significant isolation‐by‐distance effect that is likely the result of short dispersal distances and high natal and breeding philopatry of Pyrenean ptarmigan coupled with severe habitat fragmentation. Furthermore, analysis of molecular variance, principal component analysis and Bayesian analysis of genetic structuring identified the greatest amount of differentiation between the eastern and main parts of the Pyrenean chain separated by the Sègre Valley. Our data also show that the Canigou massif may host an isolated population and requires special conservation attention. We propose a management plan which includes the translocation of birds. If a sky island structure affects genetic divergence in rock ptarmigan, it may also affect the genetic structure of other sky island species having low dispersal abilities.
Reduction of protein kinase C ζ inhibits migration and invasion of human glioblastoma cells
Authors: Guo Hua , Gu Feng , Li Wenliang , Zhang Baogang , Niu Ruifang , Fu Li , Zhang Ning , Ma Yongjie 
Published: February 2009

AbstractGlioblastomas are the most aggressive forms of primary brain tumors with their tendency to invade surrounding healthy brain tissues, rendering them largely incurable. In this report, we used small‐interference RNA technology to knock down the expression of protein kinase C (PKC) ζ, which resulted in specific and massive impairment of glioblastoma cell migration and invasion. We also explained the fundamental molecular processes of glioblastoma migration and invasion in which PKCζ is a participant. The silence of PKCζ expression likewise impaired the phosphorylation of LIN‐11, Isl1 and MEC‐3 protein domain kinase (LIMK) and cofilin, which is a critical step in cofilin recycling and actin polymerization. Consistent with the defects in cell adhesion, phosphorylation of integrin β1 was also dampened. Therefore, PKCζ regulated both cytoskeleton rearrangement and cell adhesion, which contributed to cell migration. Additionally, there was down‐regulation of matrix metalloprotease‐9 expression in siPKCζ/LN‐229 cells, which coincided with decreased invasion both in vitro and in vivo. These results indicate that PKCζ is involved in the control of glioblastoma cell migration and invasion by regulating the cytoskeleton rearrangement, cell adhesion, and matrix metalloprotease‐9 expression. Collectively, these findings suggest that PKCζ is a potential therapeutic target for glioblastoma infiltration.
Alterations of myelin‐specific proteins and sphingolipids characterize the brains of acid sphingomyelinase‐deficient mice, an animal model of Niemann–Pick disease type A
Authors: Buccinnà Barbara , Piccinini Marco , Prinetti Alessandro , Scandroglio Federica , Prioni Simona , Valsecchi Manuela , Votta Barbara , Grifoni Silvia , Lupino Elisa , Ramondetti Cristina , Schuchman Edward H. , Giordana Maria Teresa , Sonnino Sandro , Rinaudo Maria Teresa 
Published: February 2009

AbstractNiemann–Pick disease (NPD) type A is a neurodegenerative disorder caused by sphingomyelin (SM) accumulation in lysosomes relying on reduced or absent acid sphingomyelinase (ASM) activity. NPD‐A patients develop progressive neurodegeneration including cerebral and cerebellar atrophy, relevant Purkinje cell and myelin deficiency with death within 3 years. ASM‘knock‐out’ (ASMKO) mice, an animal model of NPD‐A, develop a phenotype largely mimicking that of NPD‐A. The mechanisms underlying myelin formation are poorly documented in ASMKO mice. In this study we determined the content of four myelin‐specific proteins, myelin basic protein (MBP), 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase (CNP), myelin associated glycoprotein (MAG) and proteolipid protein (PLP), and that of myelin‐enriched sphingolipids in the brains of ASMKO and wild‐type mice in early stages of post‐natal (pn) life. Protein and mRNA analysis revealed that in ASMKO mice beginning from 4 post‐natal weeks (wk‐pn), the expression levels of MAG, CNP, and MBP were below those observed in wild‐type mice and the same applied to PLP at 10 wk‐pn. Moreover, at 4 wk‐pn the expression of SOX10, one of the transcription factors involved in oligodendrocyte development and maintenance was lower in ASMKO mice. Lipid analysis showed that SM and the gangliosides GM3 and GM2 accumulated in the brains of ASMKO mice, as opposed to galactocerebroside and galactosulfocerebroside that, in parallel with the mRNAs of UDP‐galactose ceramide galactosyltransferase and galactose‐3‐O‐sulfotransferase 1, the two transferases involved in their synthesis, decreased. Myelin lipid analysis showed a progressive sphingomyelin accumulation in ASMKO mice; noteworthy, of the two sphingomyelin species known to be resolved by TLC, only that with the lower Rf accumulated. The immunohistochemical analysis showed that the reduced expression of myelin specific proteins in ASMKO mice at 10 wk‐pn was not restricted to the Purkinje layer of the cerebellar cortex but involved the cerebral cortex as well. In conclusion, reduced oligodendrocyte metabolic activity is likely to be the chief cause of myelin deficiency in ASMKO mice, thus shedding light on the molecular dysfunctions underlying neurodegeneration in NPD‐A.
Lipid rafts regulate 2‐arachidonoylglycerol metabolism and physiological activity in the striatum
Authors: Maccarrone Mauro , De Chiara Valentina , Gasperi Valeria , Viscomi Maria Teresa , Rossi Silvia , Oddi Sergio , Molinari Marco , Musella Alessandra , Finazzi‐Agrò Alessandro , Centonze Diego 
Published: February 2009

AbstractSeveral G protein‐associated receptors and synaptic proteins function within lipid rafts, which are subdomains of the plasma membranes that contain high concentrations of cholesterol. In this study we addressed the possible role of lipid rafts in the control of endocannabinoid system in striatal slices. Disruption of lipid rafts following cholesterol depletion with methyl‐β‐cyclodestrin (MCD) failed to affect synthesis and degradation of anandamide, while it caused a marked increase in the synthesis and concentration of 2‐arachidonoylglycerol (2‐AG), as well as in the binding activity of cannabinoid CB1 receptors. Surprisingly, endogenous 2‐AG‐mediated control of GABA transmission was not potentiated by MCD treatment and, in contrast, neither basal nor 3,5‐Dihydroxyphenylglycine‐stimulated 2‐AG altered GABA synapses in cholesterol‐depleted slices. Synaptic response to the cannabinoid CB1 receptor agonist HU210 was however intact in MCD‐treated slices, indicating that reduced sensitivity of cannabinoid CB1 receptors does not explain why endogenous 2‐AG is ineffective in inhibiting striatal GABA transmission after cholesterol depletion. Confocal microscopy analysis suggested that disruption of raft integrity by MCD might uncouple metabotropic glutamate 5‐CB1 receptor interaction by altering the correct localization of both receptors in striatal neuron elements. In conclusion, our data indicate that disruption of raft integrity causes a complex alteration of the endocannabinoid signalling in the striatum.
Estradiol induces physical association of neuronal nitric oxide synthase with NMDA receptor and promotes nitric oxide formation via estrogen receptor activation in primary neuronal cultures
Authors: D’Anglemont de Tassigny Xavier , Campagne Céline , Steculorum Sophie , Prevot Vincent 
Published: February 2009

AbstractEstrogens and nitric oxide (NO) exert wide‐ranging effects on brain function. Recent evidence suggested that one important mechanism for the regulation of NO production may reside in the differential coupling of the calcium‐activated neuronal NO synthase (nNOS) to glutamate NMDA receptor channels harboring NR2B subunits by the scaffolding protein post‐synaptic density‐95 (PSD‐95), and that estrogens promote the formation of this ternary complex. Here, we demonstrate that 30‐min estradiol‐treatment triggers the production of NO by physically and functionally coupling NMDA receptors to nNOS in primary neurons of the rat preoptic regionin vitro. The ability of estradiol to activate neuronal NO signaling in preoptic neurons and to promote changes in protein‐protein interactions is blocked by ICI 182,780, an estrogen receptor antagonist. In addition, blockade of NMDA receptor NR2B subunit activity with ifenprodil or disruption of PSD‐95 synthesis in preoptic neurons by treatment with an anti‐sense oligodeoxynucleotide inhibited the estradiol‐promoted stimulation of NO release in cultured preoptic neurons. Thus, estrogen receptor‐mediated stimulation of the nNOS/PSD‐95/NMDA receptor complex assembly is likely to be a critical component of the signaling process by which estradiol facilitates coupling of glutamatergic fluxes for NO production in neurons.