bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement of glucose tolerance in Zucker diabetic fatty rats by long‐term treatment with the dipeptidyl peptidase inhibitor P32/98: comparison with and combination with rosiglitazone
Authors: Wargent E. , Stocker C. , Augstein P. , Heinke P. , Meyer A. , Hoffmann T. , Subramanian A. , Sennitt M. V. , Demuth H.‐U. , Arch J. R. S. , Cawthorne M. A. 
Published: February 2005

Aim:  The aim of this study was to investigate the effect of long‐term treatment with the dipeptidyl peptidase inhibitor P32/98 and its combination with rosiglitazone on blood glucose control and islet of Langerhans histology in male Zucker diabetic fatty (ZDF) rats, when treatment begins before or after the development of overt diabetes.Methods:  ZDF rats were treated with P32/98 from the age of 9, 12 or 15 weeks. Rosiglitazone maleate was given to a separate group from the age of 13 weeks. P32/98 was given to all of these rosiglitazone‐treated rats from 16 weeks of age. Rosiglitazone maleate was also given from 16 weeks of age to half the rats that were given P32/98 from 9 weeks of age. The compounds were given by oral gavage until the rats were 14 weeks old and then in the diet. The experiment was terminated at the age of 20–21 weeks. Blood glucose, plasma insulin and oral glucose tolerance were measured at intervals; islet histology was assessed terminally.Results:  P32/98 improved glucose tolerance after both single and multiple doses when treatment started at 9 weeks of age, also after the third week of treatment when treatment began at 12 or 15 weeks of age. P32/98 reduced daytime blood glucose when treatment began at 12 weeks. Treatment with rosiglitazone increased food intake and body weight, and after 2 weeks, reduced daytime blood glucose, water intake and the area under the glucose tolerance curve. A single dose of P32/98 markedly improved glucose tolerance in rosiglitazone‐treated rats. When treatment had begun at 9 weeks of age, P32/98 stimulated insulin secretion in some glucose tolerance tests. Neither P32/98 nor rosiglitazone affected pancreatic insulin content, nor did they have clear effects on islet histology.Conclusion:  P32/98 elicited a sustained improvement in glucose tolerance in both prediabetic and diabetic ZDF rats. The effects of P32/98 on glucose and insulin were similar to those of rosiglitazone, and in contrast to rosiglitazone, P32/98 did not increase food intake or body weight. However, neither compound was especially effective at improving diabetes in ZDF rats when treatment began at 9, 12 or 15 (P32/98) or 13 (rosiglitazone) weeks of age.
Weight loss‐associated changes in acute effects of nateglinide on insulin secretion after glucose loading: results of glucose loading on 2 consecutive days
Authors: Mori Y. , Mamori S. , Tajima N. 
Published: February 2005

Aim:  The aim of this study was to investigate the influence of changes in insulin resistance and early insulin secretion on the insulin secretagogic effects of nateglinide.Methods:  Oral glucose tolerance testing (OGTT, 75 g) was performed in obese patients before and after weight loss on 2 consecutive days (first day OGTT without nateglinide, second day OGTT with nateglinide), to compare any weight loss associated changes in the nateglinide‐induced insulin response to glucose loading.Results:  Reductions in visceral fat, liver fat, skeletal muscle fat and homeostasis model assessment (HOMA)‐R due to weight loss were associated with increased Δ insulin 30 min/Δ glucose 30 min (ΔI30/ΔG30), and reduced area under the curve (AUC) for plasma glucose as seen in OGTT results. Results from OGTT showed that nateglinide administration was associated with reductions in plasma glucose AUC, both before and after weight loss. Before weight loss, although there was a significant elevation of ΔI30/ΔG30 associated with nateglinide treatment, no major change in the insulin‐secreting dynamics after glucose loading was observed. After weight loss, nateglinide administration produced a significant increase in ΔI30/ΔG30, with insulin secretion peaking more quickly.Conclusion:  Insulin response to nateglinide after glucose loading varied greatly in conjunction with weight loss. This may be accounted for not only by the enhancement of early insulin response to nateglinide associated with the improvement of early insulin response with weight loss but also by the reduced visceral fat, which in turn led to reduced levels of free fatty acids in portal blood and hepatic triglycerides, as well as increased hepatic insulin clearance.
A mobile screening programme for the cardiovascular and microvascular complications of Type 2 diabetes in primary care
Authors: Sampson M. J. , Barrie P. , Dozio N. , Flatman M. , Hadley‐Brown M. , Harvey I. , Heyburn P. J. , Jones C. , Mann R. , Temple R. C. , Greenwood R. H. 
Published: February 2005

AbstractThe Diabetes National Service framework (NSF), and the quality payments in the new contract for UK General Practitioners, promote regular screening for diabetes complications. The new contract also includes immediate incentives to meet screening and quality targets, but it will be difficult to meet these targets in primary care. We have developed a mobile ‘annual review’ programme for patients with Type 2 diabetes managed solely in primary care, that screens for cardiovascular disease, hypertension, retinopathy and neuropathy at the patient's general practice, and gives written foot care, dietary advice and level 1 smoking cessation advice to all patients.
How diabetic patients think about and manage their illness in Taiwan
Authors: Lai W. A. , Lew‐Ting C.‐Y. , Chie W.‐C. 
Published: February 2005

AbstractAims Type 2 diabetes is becoming more prevalent in Taiwan. Growing evidence suggests a patient‐centred approach is more effective in facilitating self‐management than a professional‐centred one. The aim of this qualitative study was to investigate Chinese diabetic patients’ perceptions about their illness and treatment strategies to facilitate patient‐centred, culture‐sensitive clinical skills.Methods We used in‐depth interviews to collect perspectives from 22 participants recruited from a rural Taiwan community. All interviews were audio‐taped and the transcripts were analysed by editing and immersion/crystallization. Emerging themes were compared with current medical knowledge to determine their clinical significance.Results Generally, Chinese diabetic patients had variable perceptions about different treatment strategies. All agreed that dietary restriction and exercise were beneficial. The former, mainly understood as reducing carbohydrate intake, was thought to be most important; exercise, to the point of sweating, was seen as a way to eliminate pharmaceutical toxins. Taking medicine was regarded with ambivalent attitudes due to concerns about adverse effects (especially renal injury).Conclusions Patients regarded all treatment strategies as integrative and intertwined in daily life. There are three misconceptions which we found should be clarified during medical consultations: (i) focusing on sugar‐control only; (ii) benefit of sweating to eliminate toxins; (iii) fear of renal toxicity of hypoglycaemic agents. The renaming of diabetes, to such as ‘metabolic syndrome’, may bring new, acceptable insight to Chinese diabetic patients.
Insulin sensitivity at diagnosis of Type 2 diabetes is not associated with subsequent cardiovascular disease (UKPDS 67)
Authors: Adler A. I. , Levy J. C. , Matthews D. R. , Stratton I. M. , Hines G. , Holman R. R. 
Published: February 2005

AbstractAims  Insulin resistance is common in Type 2 diabetes which, in turn, is associated with a markedly increased risk of cardiovascular disease. Whether insulin sensitivity measured after diagnosis of diabetes is associated with incident cardiovascular disease was evaluated in this prospective study.Methods  Three thousand five hundred and eighty‐two subjects with newly diagnosed diabetes, recruited to the UK Prospective Diabetes Study (UKPDS), free of cardiovascular disease, and with complete information on insulin sensitivity and potential confounders, were followed prospectively to the first occurrence of (i) fatal or non‐fatal myocardial infarction, MI (ii) fatal or non‐fatal stroke, and (iii) coronary heart disease, CHD (fatal or non‐fatal MI, sudden death or ischaemic heart disease). Insulin sensitivity was measured by Homeostatic Model Assessment (HOMA).Results  Insulin sensitivity as measured by HOMA was not associated with subsequent MI, stroke, or CHD in univariate or multivariate models controlling for age, sex, ethnicity, HbA1c, body mass index, plasma triglycerides, cholesterol and smoking. The hazard ratio associated with a doubling of insulin sensitivity with fatal or non‐fatal MI in a multivariate model was 0.92 (95% confidence interval, CI, 0.80–1.05). These results were not changed by the exclusion of overweight patients randomized to metformin.Discussion  Estimation of insulin sensitivity provides no additional useful information with respect to the risk of the first occurrence of cardiovascular disease in patients with newly diagnosed Type 2 diabetes. Among patients with Type 2 diabetes, insulin resistance is not a risk factor for cardiovascular disease.
Routine diagnosis of Type 2 diabetes mellitus in general practice and hospitals: how do patients differ?
Authors: Drivsholm T. , Olivarius N. de F. 
Published: February 2005

AbstractObjective  To study how Type 2 diabetic patients diagnosed by routine case‐finding in primary care differ from patients diagnosed in secondary care with regard to clinical characteristics, symptom‐burden and prevalence of complications.Research design and methods  A Danish population‐based sample of 1633 newly diagnosed Type 2 diabetic patients, of whom we had detailed information of sociodemographic and clinical characteristics, biochemical measurements, and complications among 1381. Blood and urine analyses were centralized.Results  Of the patients, 76.8% were diagnosed in general practice. Compared with those diagnosed in secondary care, patients diagnosed in general practice on average had higher levels of cardiovascular risk factors (BMI: 29.8 vs. 28.5 kg/m2, P < 0.001; systolic blood pressure: 149.4 vs. 143.2 mmHg, P < 0.001; diastolic blood pressure: 85.2 vs. 82.5 mmHg, P < 0.001; haemoglobin A1c: 10.1 vs. 8.4%, P < 0.0001; total cholesterol: 6.4 vs. 6.1 mmol/l, P < 0.01), more frequently presented with hyperglycaemic symptoms (80.1 vs. 63.4%, P < 0.0001), while fewer had macrovascular complications (28.5 vs. 43.6%, P < 0.0001).Conclusions  Judged from their risk profile, Type 2 diabetic patients diagnosed in primary care are at no less risk of developing diabetic complications than those diagnosed in secondary care.
Improvement of glycaemic control with rebound following orlistat initiation and cessation associated with minimal weight change
Authors: González S. , Kilpatrick E. S. , Atkin S. L. 
Published: February 2005

AbstractA 57‐year‐old Caucasian woman with Type 2 diabetes treated for seven years with diet and oral combination hypoglycaemic therapy was referred because of the progressive deterioration of glycaemic control.She was obese (77 kg, BMI = 39.9), hypertensive, hypercholesterolaemic with marked osmotic symptoms (HbA1c 12.2%), therefore she was started on insulin (Human Mixtard 30 b.d.) with metformin therapy. Dietary counselling, recommendations to increase physical activity, and supervised self‐injection technique with titration of her insulin were also provided. She was routinely followed‐up to assess her progress.Two years later, her glycaemic control remained suboptimal. Average HbA1c was 10.4% despite an increasingly high dose of insulin (94 units/day) although it improved when metformin was increased to 1 g t.d.s. (HbA1c = 9.3%). Her BMI progressively rose from 39.9 to 42.1 (77 to 82.5 kg) despite dietary advice.A trial of orlistat (three months) was commenced, after intensive dietary counselling, that reduced her body weight by 1.5 kg (2% reduction, BMI 41.3). However, her HbA1c improved by 0.5% (from 9.3 to 8.8%). Six months after orlistat was stopped her HbA1c rose to 10.5% and weight increased to 81.8 kg (BMI 41.8). Despite the orlistat treatment broaching NICE guidelines should it have been continued?
Neutral Property Taxation
Authors: ARNOTT RICHARD 
Published: February 2005

AbstractA major difficulty in implementing land/site value taxation is imputing the land value of built‐on sites. The literature has focused on two alternatives. The first, residual site value, measures postdevelopment site value as property value less structure value, with structure value measured as depreciated construction costs. Residual site value would be relatively easy to estimate, but a residual site value tax system, which taxes land value before development and residual site value after development at the same rate is distortionary, discouraging density. The second, raw site value, measures postdevelopment site value as “what the land would be worth were there no building on the site (though in fact there is).” Raw site value taxation is neutral (does not distort the timing and density of development), but the estimation of postdevelopment raw site value would be complex so that assessment would likely be less fair and more arbitrary, contentious, and prone to abuse. This paper asks the question: Is it not possible to design a property tax system (taxation of predevelopment land value, postdevelopment structure value, and postdevelopment site value at possibly different rates) that employs the administratively simpler residual definition of postdevelopment site value and achieves neutrality? Under restrictive assumptions and subject to an important qualification, the paper provides an affirmative answer, and characterizes the tax rates that achieve neutrality. It also briefly discusses issues of practical implementation.
Leading by Example and International Collective Action
Authors: DE OLIVEIRA ANDRÉ ROSSI , FARIA JOÃO RICARDO , ARCE M. DANIEL G. 
Published: February 2005

AbstractThis paper investigates leading by example as a policy prescription for international collective action to provide summation public goods. A country leads by example by committing to a minimal level of provision, and by matching higher contributions there beyond. In an evolutionary game‐theoretic setting, we establish conditions for leading by example to be a neutrally stable strategy; i.e., to noncooperatively implement the cooperative outcome. These conditions are related to the degree of concavity of the contributors' utility functions and the incentives for free riding. They can be tested against empirical estimates of the public benefits of an international regime.
Externality Policy Reform: A General Equilibrium Analysis
Authors: MURTY SUSHAMA , RUSSELL R. ROBERT 
Published: February 2005

AbstractWe characterize Pareto‐improving and equilibrium‐preserving policy reforms in a second‐best (Diamond/Mirrlees) world with a consumption externality. A counterintuitive finding is that, starting from an initial equilibrium with no direct quantity control on the externality, it is possible that all Pareto‐improving and equilibrium‐preserving directions of change require an increase in a negative externality. We provide intuition for these results by establishing a nexus between Guesnerie's approach to designing (tax) policy reforms and the standard Kuhn–Tucker technique for identifying the manifold of feasible Pareto‐optimal states, given the instruments available to the policy maker.
Combination therapy
Authors: Ingemarsson Ingemar 
Published: February 2005

Objective  Inhibiting preterm labour at extremely early gestations.Design  Observational study. Case reports.Setting  Perinatal Centre Lund University Hospital, South Sweden.Population  Twenty‐five women (13 cases with intact membranes and 12 cases with ruptured) with threatened preterm labour and advanced cervical status before 26 completed weeks of gestation.Methods  A combination of different drugs was used. Atosiban, an oxytocin antagonist, was the first line drug and was given as an infusion for several days as required. Supportive therapy was also given to most women with subcutaneous injections of the β‐receptor agonist terbutaline (0.25 mg up to six times a day); sulindac, a prostaglandin synthetase inhibitor (200 mg one to two times a day up to a week); and broad‐spectrum antibiotics (metronidazole and cefuroxime intravenously for three days and thereafter oral therapy).Main outcome measures  Prolongation of pregnancy more than 48 hours or 7 days. Neonatal survival.Results  Prolongation of pregnancy for more than 48 hours to enable administration of corticosteroid therapy was obtained in all but three cases. Eight women were delivered after more than a week from admission. Three neonates died at birth due to obstetric complication or sepsis. The other neonates had normal pH in cord or venous blood at birth. No severe side effects were recorded and in no case did the treatment have to be discontinued due to side effects.Conclusion  The policy described here is not evidence based, relating only to clinical observations, and as such is of very limited value. However, it seems that with this combined approach to management, some days can be gained by achieving full effect of corticosteroid treatment and prolongation of the pregnancy, hopefully reducing time in the neonatal intensive care in these critical cases. No severe side effects were reported.
LFRFamides: a novel family of parasitation‐induced ‐RFamide neuropeptides that inhibit the activity of neuroendocrine cells in Lymnaea stagnalis
Authors: Hoek R. M. , Li K. W. , Van Minnen J. , Lodder J. C. , De Jong‐Brink M. , Smit A. B. , Van Kesteren R. E. 
Published: February 2005

AbstractWe report the characterization of a cDNA encoding a novel ‐RFamide neuropeptide precursor that is up‐regulated during parasitation in the snail Lymnaea stagnalis. Processing of this precursor yields five structurally related neuropeptides, all but one ending with the C‐terminal sequence ‐LFRFamide, as was confirmed by direct mass spectrometry of brain tissue. The LFRFamide gene is expressed in a small cluster of neurons in each buccal ganglion, three small clusters in each cerebral ganglion, and one cluster in each lateral lobe of the cerebral ganglia. Application of two of the LFRFamide peptides to neuroendocrine cells that control either growth and metabolism or reproduction induced similar hyperpolarizing K+‐currents, and inhibited electrical activity. We conclude that up‐regulation of inhibitory LFRFamide neuropeptides during parasitation probably reflects an evolutionary adaptation that allows endoparasites to suppress host metabolism and reproduction in order to fully exploit host energy recourses.
Cellular and subcellular calcium accumulation during glutamate‐induced injury in cerebellar granule neurons
Authors: Ward Manus W. , Kushnareva Yulia , Greenwood Sam , Connolly Christopher N. 
Published: February 2005

AbstractWe have investigated the role of Ca2+ accumulation and neuronal injury in cerebellar granule neurons after glutamate receptor overactivation. After the removal of the free cytosolic Ca2+ we identified an extensive second Ca2+ fraction (SCF) that is retained within the neurons after glutamate receptor overactivation. The SCF reaches a plateau within 10 min with the magnitude of this SCF accumulation reflecting the extent of the neuronal injury that occurs within the neurons. The existence of this SCF is sensitive to both NMDA receptor antagonists and mitochondrial inhibitors but is unaffected by agents that deplete endoplasmic reticulum Ca2+, indicating that this Ca2+ fraction may be located within the mitochondria. Through the isolation of mitochondria from cerebellar granule neurons treated with glutamate we have shown that the majority of the SCF is mitochondrial in location. On the removal of the glutamate stimulus the SCF recovers at a slower rate than the free Ca2+ concentration within the neuron. This is intriguing, as it implies a capacity to remember previous excitatory events. Most significantly we have shown that a short pre‐application of subthreshold glutamate or kainate blocks both SCF Ca2+ accumulation and extensive neuronal injury in response to high concentrations of glutamate. These findings may be relevant to the observations of pre‐conditioning in the brain and heart.
Increased cyclin E expression may obviate the role of cyclin D1 during brain development in cyclin D1 knockout mice
Authors: Chen Zhiguo , Duan Rui‐Sheng , Zhu Yu , Folkesson Ronnie , Albanese Chris , Winblad Bengt , Zhu Jie 
Published: February 2005

AbstractCyclins D and E play critical roles during the G1 phase of mammalian cell division. Cyclin D1 expression is high and expected to play an important role during mouse brain development. However, in the present study, we found no difference in CNS morphology between cyclin D1 knockout (KO) and control wild‐type mice at the ages of 1, 4 and 12 months. Analysis of protein expression in embryonic brains revealed that cyclin E is obviously increased in cyclin D1 KO mice at 13.5 days post coitum. At the same age a high level of cyclin D1 expression is detected in the embryonic brain of wild‐type mice. The data indicate that enhanced cyclin E protein expression in cyclin D1 KO mice may obviate the role of cyclin D1 and contribute to the normal brain development of cyclin D1 KO mice.
Axonal transport of the cellular prion protein is increased during axon regeneration
Authors: Moya Kenneth L. , Hässig Raymonde , Breen Kieran C. , Volland Hervé , Di Giamberardino Luigi 
Published: February 2005

AbstractThe cellular prion protein, PrPc, is a glycosylphosphatidylinositol‐anchored cell surface glycoprotein and a protease‐resistant conformer of the protein may be the infectious agent in transmissible spongiform encephalopathies. PrPc is localized on growing axons in vitro and along fibre bundles that contain elongating axons in developing and adult brain. To determine whether the growth state of axons influenced the expression and axonal transport of PrPc, we examined changes in the protein following post‐traumatic regeneration in the hamster sciatic nerve. Our results show (1) that PrPc in nerve is significantly increased during nerve regeneration; (2) that this increase involves an increase in axonally transported PrPc; and (3) that the PrPc preferentially targeted for the newly formed portions of the regenerating axons consists of higher molecular weight glycoforms. These results raise the possibility that PrPc may play a role in the growth of axons in vivo, perhaps as an adhesion molecule interacting with the extracellular environment through specialized glycosylation.