bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five‐year risk of developing clinical diabetes after first myocardial infarction; the FINAMI study
Authors: Pajunen P. , Koukkunen H. , Ketonen M. , Jerkkola T. , Immonen‐Räihä P. , Kärjä‐Koskenkari P. , Mähönen M. , Niemelä M. , Kuulasmaa K. , Palomäki P. , Mustonen J. , Lehtonen A. , Arstila M. , Vuorenmaa T. , Lehto S. , Miettinen H. , Juolevi A. , Torppa J. , Tuomilehto J. , Kesäniemi Y. A. , Pyörälä K. , Salomaa V. 
Published: August 2005

AbstractAim  To investigate the incidence of clinical diabetes as determined by the incidence of diabetes drug reimbursements within a 5‐year period after the first myocardial infarction (MI) in patients who were non‐diabetic at the time of their first MI.Research design and methods  A population‐based MI register, FINMONICA/FINAMI, recorded all coronary events in persons of 35–64 years of age between 1988 and 2002 in four study areas in Finland. These records were used to identify subjects sustaining their first MI (n = 2632). Participants of the population‐based risk factor survey FINRISK (surveys 1987, 1992, 1997 and 2002), who did not have diabetes or a history of MI, served as the control group (n = 7774). The FINMONICA/FINAMI study records were linked with the National Social Security Institute's drug reimbursement records, which include diabetes medications, using personal identification codes. The records were used to identify subjects who developed diabetes during the 5‐year follow‐up period (n = 98 in the MI group and n = 79 in the control group).Results  Sixteen per cent of men and 20% of women sustaining their first MI were known to have diabetes and thus were excluded from this analysis. Non‐diabetic men having a first MI were at more than twofold {hazard ratio (HR) 2.3 [95% confidence interval (CI) 1.6–3.4]}, and women fourfold [HR 4.3 (95% CI 2.4–7.5)], risk of developing diabetes mellitus during the next 5 years compared with the control population without MI.Conclusions  Many patients who do not have diabetes at the time of their first MI develop diabetes in the following 5 years.
Repaglinide treatment amplifies first‐phase insulin secretion and high‐frequency pulsatile insulin release in Type 2 diabetes
Authors: Hollingdal M. , Sturis J. , Gall M.‐A. , Damsbo P. , Pincus S. , Veldhuis J. D. , Pørksen N. , Schmitz O. , Juhl C. B. 
Published: August 2005

AbstractAims/hypothesis  First‐phase insulin release and coordinated insulin pulsatility are disturbed in Type 2 diabetes. The present study was undertaken to explore a possible influence of the oral prandial glucose regulator, repaglinide, on first‐phase insulin secretion and high‐frequency insulin pulsatility in Type 2 diabetes.Methods  We examined 10 patients with Type 2 diabetes in a double‐blind placebo‐controlled, cross‐over design. The participants were treated for 6 weeks with either repaglinide [2–9 mg/day (average 5.9 mg)] or placebo in random order. At the end of each treatment period, first‐phase insulin secretion was measured. Entrainment of insulin secretion was assessed utilizing 1‐min glucose bolus exposure (6 mg/kg body weight every 10 min) for 60 min during (A) baseline conditions, i.e. 12 h after the last repaglinide/placebo administration, and (B) 30 min after an oral dose of 0.5 mg repaglinide/placebo with subsequent application of time‐series analyses.Results  Postprandial (2‐h) blood glucose was significantly reduced by repaglinide after 5 weeks of treatment (P < 0.001). The fall in HbA1c did not reach statistical significance (P = 0.07). AUCins,0−12 min during the first‐phase insulin secretion test was enhanced (P < 0.05). In addition, glucose entrained insulin secretory burst mass and amplitude increased markedly (burst mass: repaglinide, 44.4 ± 6.0 pmol/l/pulse vs. placebo, 31.4 ± 3.3 pmol/l/pulse, P < 0.05; burst amplitude: repaglinide, 17.7 ± 2.4 pmol/l/min vs. placebo, 12.6 ± 1.3 pmol/l/min, P < 0.05) while basal insulin (non‐pulsatile) secretion was unaltered. After acute repaglinide exposure (0.5 mg) basal insulin secretion increased significantly (P < 0.05). Neither acute nor chronic repaglinide administration influenced frequency or regularity of insulin pulses during entrainment.Conclusion/interpretation  Repaglinide augments first‐phase insulin secretion as well as high‐frequency insulin secretory burst mass and amplitude during glucose entrainment in patients with Type 2 diabetes, while regularity of the insulin release process was unaltered.Diabet. Med. (2005)
Evaluation of the association between the EQ‐5Dindex (health‐related utility) and body mass index (obesity) in hospital‐treated people with Type 1 diabetes, Type 2 diabetes and with no diagnosed diabetes
Authors: Lee A. J. , Morgan C. Ll. , Morrissey M. , Wittrup‐Jensen K. U. , Kennedy‐Martin T. , Currie C. J. 
Published: August 2005

AbstractAims  The purpose of this study was to characterize the impact of body mass index (BMI) on health‐related utility for patients with Type 1 and Type 2 diabetes and those without diabetes.Methods  The study was conducted in Cardiff and the Vale of Glamorgan, Wales, UK. Health‐related utility was measured using the EQ‐5Dindex. Patients from the Health Outcomes Data Repository (HODaR) were surveyed by postal questionnaire either 6 weeks post discharge for in‐patients or at out‐patient clinics between January 2002 and July 2003. BMI was calculated from self‐reported data within the survey. Patients with diabetes were identified by a previous history of an in‐patient admission with diabetes or as an out‐patient with diabetes recorded as a coexisting diagnosis.Results  Questionnaires were returned from 27 924 patients of whom 2575 had diabetes. Increasing BMI was found to reduce utility in all three groups. BMI was significantly greater for those with Type 2 diabetes compared with those with Type 1, and those without diabetes (P < 0.001). Multiple regression analysis demonstrated that both BMI and diabetes status had a significant effect on utility. However, the rate of change of utility attributable to BMI was not found to be significantly different between the various groups.Conclusions  Obesity negatively impacts upon health‐related utility and thus quality of life for all patient groups. There was no significant difference in the effect of obesity on utility between those with and without diabetes.
Prevalence of Type 2 diabetes in urban and rural Chinese populations in Qingdao, China
Authors: Dong Y. , Gao W. , Nan H. , Yu H. , Li F. , Duan W. , Wang Y. , Sun Bin , Qian R. , Tuomilehto J. , Qiao Q. 
Published: August 2005

AbstractAims  To determine the prevalence of diabetes in the Chinese adult population in rural and urban areas of Qingdao city.Methods  A population‐based cross‐sectional study of diabetes was performed in 12 436 (5346 men) Chinese adults (20–74 years old) from 2001 to 2002. Fasting capillary whole blood glucose test (FCG) was performed in all participants and a 2‐h 75‐g oral glucose tolerance test in those with FCG ≥ 6.1 mmol/l following initial screening. The 1999 World Health Organization diagnostic criteria for diabetes were used.Results  The age‐standardized prevalence of diabetes was 6.1% (4.1% for undiagnosed and 2.1% for previously known diabetes) in adults aged 20–74 years. Diabetes prevalence increased with age up to the oldest age group (70–74); in subjects over 50 years of age, the prevalence reached 10%. Men tended to have a higher prevalence of known diabetes than women, whereas the prevalence of undiagnosed diabetes was lower in men than in women (4.6% vs. 3.3%, d.f. = 1, P = 0.001). Diabetes was more prevalent in the urban than in the rural population (6.9% vs. 5.6%, d.f. = 1, P < 0.001). However, the proportion of undiagnosed diabetes was higher in the rural than in the urban areas (70.5% vs. 58.0%, d.f. = 1, P < 0.001).Conclusions  The prevalence of Type 2 diabetes in Qingdao city is moderately high, but much higher than reported in 1996. The large proportion of undiagnosed cases of diabetes indicates the lack of public awareness of diabetes and shortage of medical facilities. In view of the huge population in China, the results of this study emphasize the need to improve the early detection and prevention of diabetes in China to prevent the emerging diabetes epidemic.
The perils of procrastination: effects of early vs. delayed detection and treatment of incipient Charcot fracture
Authors: Chantelau E. 
Published: August 2005

AbstractBackground  At the onset of acute diabetic Charcot foot, therapeutic intervention may be delayed because plain X‐rays may not show fractures.Aim of the study  To assess the clinical course of acute Charcot foot in 24 patients without evidence of definite fractures on the first X‐ray after onset of symptoms, who were referred to the foot clinic for diagnosis and treatment either early or delayed, i.e. before or after definite fractures were detectable on repeat X‐rays.Patients and methods  Eleven patients were referred early (incipient Charcot foot, case group), and 13 patients were referred delayed (overt Charcot foot, control group). In the foot clinic, both groups were immediately treated with off‐loading and total contact casting. After the healing process of the Charcot foot was complete, the extent of fractures and subsequent deformities were evaluated.Results  Based on X‐rays at the onset of symptoms, in 19 of the 24 patients the condition had been misdiagnosed prior to referral (in 11 patients as sprain injury). Additional imaging techniques (MRI, CT scan or bone scintigraphy) had been performed in 10 patients prior to referral. While these techniques had been used more frequently in the cases vs. the controls (P = 0.012), misdiagnosis was less frequent in the cases vs. the controls (P = 0.013). Only one out of 11 case patients developed extended foot fractures and severe deformity, vs. 12 out of 13 control patients (P < 0.001).Conclusion  Early detection of incipient Charcot foot is facilitated by imaging techniques other than plain X‐rays. Immediate off‐loading of incipient Charcot foot appears to minimize fractures and incapacitating deformities.
Interventions to promote optimal health outcomes in children with Type 1 diabetes—are they effective?
Authors: Northam E. A. , Todd S. , Cameron F. J. 
Published: August 2005

AbstractThe incidence of Type 1 diabetes is increasing worldwide, imposing enormous public health costs, as well as profoundly affecting individual quality of life. There is evidence that psychological problems are increased in children with diabetes and this morbidity is often associated with poor metabolic control. Specific risk factors for this dual morbidity are emerging from empirical studies. The next challenge is to identify effective interventions for use with children at risk for adverse mental and physical health outcomes. The intervention literature is reviewed. It is noted that most studies have used diabetes‐specific, unstandardized interventions in groups of adolescents, with few interventions trialled with younger children. No study has targeted a specific psychological disorder such as behaviour problems or depression, both of which are known to be increased in children with diabetes and for which effective standardized interventions are available. Attention is drawn to methodological limitations in many of the studies conducted to date and suggestions made to reduce these in future interventions attempting to reduce the burden of illness in children with diabetes.
Novel polymorphisms in the GCKR gene and their influence on glucose and insulin levels in a Danish twin population
Authors: Køster B. , Fenger M. , Poulsen P. , Vaag A. , Bentzen J. 
Published: August 2005

AbstractAim  The glucokinase regulatory protein gene is a candidate gene for Type 2 diabetes. This study reveals three new polymorphisms and examines the impact of one new and one known polymorphism on insulin secretion and parameters associated with the insulin resistance syndrome in Danish twins with different degrees of glucose tolerance.Methods  Single nucleotide polymorphism detection was performed in 20 healthy subjects and in 20 subjects with Type 2 diabetes. The effect of the polymorphisms on lipid, glucose and insulin measures was studied in 566 same‐sex twins aged 55–74 years.Results  The new nucleotide (nt) 363 polymorphism was found only in subjects with impaired glucose tolerance and Type 2 diabetes. The nt 11216 polymorphism influenced insulin measured at 120 min during an oral glucose tolerance test (OGTT). Subjects with genotype C11216C/T11216C had 21% higher insulin values (P < 0.05) than subjects with genotype T11216T. In twins discordant for this genotype, the C‐allele was associated with significantly higher plasma insulin levels at all time points during the OGTT, higher β‐cell function and lower plasma glucose levels during the OGTT.Conclusion  The C‐allele of nt 11216 polymorphism was associated with increased insulin secretion, and may therefore exert a potentially protective effect against Type 2 diabetes. This remains to be shown in a larger study population.
Common promoter polymorphism in monocyte differentiation antigen CD14 is associated with serum triglyceride levels and body mass index in non‐diabetic individuals
Authors: Shin H. D. , Park K. S. , Park B. L. , Cheong H. S. , Cho Y. M. , Lee H. K. , Lee J.‐Y. , Lee J.‐K. , Kim H. T. , Han B. G. , Kim J. W. , Koh I. , Kim Y. J. , Oh B. , Kimm K. , Park C. 
Published: August 2005

AbstractAims  Growing evidence supports the hypothesis that chronic low‐grade inflammation related to innate immunity may play an important role in the pathophysiology of Type 2 diabetes mellitus (T2DM). The monocyte differentiation antigen CD14 gene (CD14) acts as the receptor for lipopolysaccharide (LPS) and augments monocyte/macrophage inflammatory responses.Methods  We have sequenced the gene, including all exons, exon/intron boundaries, and the −1.5 kb of the 5′ flanking region. Two common loci (minor allele frequency > 0.05) were genotyped in 775 T2DM patients and 316 control subjects recruited in the Korean T2DM Study.Results  Eight polymorphisms, including four non‐synonymous forms, were identified in CD14. No polymorphisms were found in association with T2DM. However, one common promoter SNP (−260T>C) was significantly associated with both the serum triglyceride level (TG) and body mass index (BMI) in non‐diabetic control subjects. Individuals who carried the minor allele (C) had higher TG levels (1.65 ± 0.81 vs. 1.46 ± 0.80 mmol/l; P = 0.0007) and BMI (23.96 ± 3.00 vs. 23.28 ± 3.22 kg/m2; P = 0.04) as compared with subjects carrying T/T genotypes.Conclusion  Our data suggest that lipid metabolism and obesity, important pathophysiological elements of T2DM and the metabolic syndrome, are regulated by complex mechanisms that include the CD14 gene polymorphism‐mediated genetic propensity to non‐specific inflammatory responses.
Alcohol is a potent stimulant of immature neuronal networks: implications for fetal alcohol spectrum disorder
Authors: Galindo Rafael , Zamudio Paula A. , Valenzuela C. Fernando 
Published: August 2005

AbstractEthanol consumption during development affects the maturation of hippocampal circuits by mechanisms that are not fully understood. Ethanol acts as a depressant in the mature CNS and it has been assumed that this also applies to immature neurons. We investigated whether ethanol targets the neuronal network activity that is involved in the refinement of developing hippocampal synapses. This activity appears during the growth spurt period in the form of giant depolarizing potentials (GDPs). GDPs are generated by the excitatory actions of GABA and glutamate via a positive feedback circuit involving pyramidal neurons and interneurons. We found that ethanol potently increases GDP frequency in the CA3 hippocampal region of slices from neonatal rats. It also increased the frequency of GDP‐driven Ca2+ transients in pyramidal neurons and increased the frequency of GABAA receptor‐mediated spontaneous postsynaptic currents in CA3 pyramidal cells and interneurons. The ethanol‐induced potentiation of GABAergic activity is probably the result of increased quantal GABA release at interneuronal synapses but not enhanced neuronal excitability. These findings demonstrate that ethanol is a potent stimulant of developing neuronal circuits, which might contribute to the abnormal hippocampal development associated with fetal alcohol syndrome and alcohol‐related neurodevelopmental disorders.
ATP‐sensitive potassium channel opener iptakalim protected against the cytotoxicity of MPP+ on SH‐SY5Y cells by decreasing extracellular glutamate level
Authors: Hu Li‐Fang , Wang Sen , Shi Xue‐Ru , Yao Hong‐Hong , Sun Ye‐Hong , Ding Jian‐Hua , Liu Shu‐Yi , Hu Gang 
Published: August 2005

AbstractMounting evidence reveals that ATP‐sensitive potassium (KATP) channel openers (KCOs) exert significant neuroprotection in vivo and in vitro in several models of Parkinson's disease (PD). However, the mechanisms are not well understood. In this study, we demonstrated that SH‐SY5Y cells expressed mRNA and proteins for Kir6.1, Kir6.2, SUR1 and SUR2 subunits of KATP channels. Moreover, our results showed that 1‐methyl‐4‐phenyl‐pyridinium ion (MPP+) induced up‐regulation of mRNA for the Kir6.2 subunit and down‐regulation of SUR1. It was further found that pretreatment with iptakalim, a novel KATP channel opener, could attenuate increased extracellular glutamate level and decreased cell survival in SH‐SY5Y cell culture after exposure to MPP+. Trans‐pyrrolidine‐2, 4‐dicarboxylic acid (t‐PDC), a glutamate transporter inhibitor, partially blocked the effect of iptakalim decreasing extracellular glutamate level. Additionally, iptakalim prevented MPP+‐induced inhibition of glutamate uptake in primary cultured astrocytes. The beneficial effects of iptakalim on glutamate uptake of astrocytes were abolished by selective mitochondrial KATP (mitoKATP) channel blocker 5‐HD. These results suggest (i) KATP channel dysfunction may be involved in the mechanisms of MPP+‐induced cytotoxicity and (ii) iptakalim may modulate glutamate transporters and subsequently alleviate the increase of extracellular glutamate levels induced by MPP+ through opening mitoKATP channels, thereby protecting SH‐SY5Y cells against MPP+‐induced cytotoxicity.
Netrin induces down‐regulation of its receptor, Deleted in Colorectal Cancer, through the ubiquitin–proteasome pathway in the embryonic cortical neuron
Authors: Kim Tae‐Hong , Lee Hyun Kyoung , Seo In Ae , Bae Hae Rahn , Suh Duk Joon , Wu Jane , Rao Yi , Hwang Kyu‐Geun , Park Hwan Tae 
Published: August 2005

AbstractThe proper regulation of temporal and spatial expression of the axon guidance cues and their receptors is critical for the normal wiring of nervous system during development. Netrins, a family of secreted guidance cues, are involved in the midline crossing of spinal commissural axons and in the guidance of cortical efferents. Axons normally lose the responsiveness to their attractants when they arrive at their targets, where the attractant is produced. However the molecular mechanism is still unknown. We investigated the molecular mechanism of down‐regulation of netrin‐1 signaling in the embryonic cortical neurons. Netrin‐1 induced the ubiquitination and proteolytic cleavage of Deleted in Colorectal Cancer (DCC), a transmembrane receptor for netrin, in dissociated cortical neurons. A dramatic decrease of DCC level particularly on the cell surface was also observed after netrin‐1 stimulation. Specific ubiquitin–proteasome inhibitors prevented the netrin‐induced DCC cleavage and decrease of cell surface DCC. We suggest that the ligand‐mediated down‐regulation of DCC might participate in the loss of netrin‐responsiveness in the developing nervous system.
Androgens activate mitogen‐activated protein kinase signaling: Role in neuroprotection
Authors: Nguyen Thuy‐Vi V. , Yao Mingzhong , Pike Christian J. 
Published: August 2005

AbstractRecent evidence indicates that testosterone is neuroprotective, however, the underlying mechanism(s) remains to be elucidated. In this study, we investigated the hypothesis that androgens induce mitogen‐activated protein kinase (MAPK) signaling in neurons, which subsequently drives neuroprotection. We observed that testosterone and its non‐aromatizable metabolite dihydrotestosterone (DHT) rapidly and transiently activate MAPK in cultured hippocampal neurons, as evidenced by phosphorylation of extracellular signal‐regulated kinase (ERK)‐1 and ERK‐2. Importantly, pharmacological suppression of MAPK/ERK signaling blocked androgen‐mediated neuroprotection against β‐amyloid toxicity. Androgen activation of MAPK/ERK and neuroprotection also was observed in PC12 cells stably transfected with androgen receptor (AR), but in neither wild‐type nor empty vector‐transfected PC12 cells. Downstream of ERK phosphorylation, we observed that DHT sequentially increases p90 kDa ribosomal S6 kinase (Rsk) phosphorylation and phosphorylation‐dependent inactivation of Bcl‐2‐associated death protein (Bad). Prevention of androgen‐induced phosphorylation of Rsk and Bad blocked androgen neuroprotection. These findings demonstrate AR‐dependent androgen activation of MAPK/ERK signaling in neurons, and specifically identify a neuroprotective pathway involving downstream activation of Rsk and inactivation of Bad. Elucidation of androgen‐mediated neural signaling cascades will provide important insights into the mechanisms of androgen action in brain, and may present a framework for therapeutic intervention of age‐related neurodegenerative disorders.
Two types of detergent‐insoluble, glycosphingolipid/cholesterol‐rich membrane domains from isolated myelin
Authors: Arvanitis Dina N. , Min Weixian , Gong Yanping , Heng Yew M. , Boggs Joan M. 
Published: August 2005

AbstractTwo different types of low‐density detergent‐insoluble glycosphingolipid‐enriched membrane domain (DIG) fractions were isolated from myelin by extraction with Triton X‐100 (TX‐100) in 50 mM sodium phosphate buffer at room temperature (20°C) (procedure 1), in contrast to a single low‐density fraction obtained by extraction with TX‐100 in Tris buffer containing 150 mM NaCl and 5 mM EDTA at 4°C (procedure 2). Procedure 1 has been used in the past by others for myelin extraction to preserve the cytoskeleton and/or radial component of oligodendrocytes and myelin, whereas procedure 2 is now more commonly used to isolate myelin DIG fractions. The two DIG fractions obtained by procedure 1 gave opaque bands, B1 and B2, at somewhat lower and higher sucrose density respectively than myelin itself. The single DIG fraction obtained by procedure 2 gave a single opaque band at a similar sucrose density to B1. Both B1 and B2 had characteristics of lipid rafts, i.e. high galactosylceramide and cholesterol content and enrichment in GPI‐linked 120‐kDa neural cell adhesion molecule (NCAM)120, as found by others for the single low‐density DIG fraction obtained by procedure 2. However, B2 had most of the myelin GM1 and more of the sulfatide than B1, and they differed significantly in their protein composition. B2 contained 41% of the actin, 100% of the tubulin, and most of the flotillin‐1 and caveolin in myelin, whereas B1 contained more NCAM120 and other proteins than B2. The single low‐density DIG fraction obtained by procedure 2 contained only low amounts of actin and tubulin. B1 and B2 also had size‐isoform selectivity for some proteins, suggesting specific interactions and different functions of the two membrane domains. We propose that B1 may come from non‐caveolar raft domains whereas B2 may derive from caveolin‐containing raft domains associated with cytoskeletal proteins. Some kinases present were active on myelin basic protein suggesting that the DIGs may come from signaling domains.