bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardioprotection with pioglitazone is abolished by nitric oxide synthase inhibitor in ischemic rabbit hearts–comparison of the effects of pioglitazone and metformin
Authors: Kawabata Hitoshi , Ishikawa Kinji 
Published: July 2003

AbstractBackgroundThe effects of two drugs representing different classes of antidiabetic pharmacology (pioglitazone, a thiazolidinedione; and metformin, a biguanide) on the myocardial metabolism in the ischemia are poorly understood.MethodsTo test the hypothesis that cardioprotection of pioglitazone and metformin is associated with nitric oxide (NO), we studied the high energy phosphate metabolism by 31P‐nuclear magnetic resonance (NMR) in isolated rabbit hearts. Forty‐five minutes of continuous normothermic global ischemia was carried out. Pioglitazone or metformin was administered at the beginning, 60 min prior to the global ischemia, with or without the nitric oxide synthase inhibitor, L‐NAME, administered 5 min or 60 min prior to the ischemia. In the first experiment, whether NO was produced or not by administration of pioglitazone, for the prevention of myocardial ischemic injury, was investigated. Hearts of male Japanese white rabbits were divided into 4 experimental groups: the control (C) group, the P group consisting of pioglitazone treatment, the P + L5 group consisting of pioglitazone treatment with L‐NAME (5 min before ischemia), and the P + L60 group consisting of pioglitazone treatment with L‐NAME (60 min before ischemia). In the next experiment, a comparison between the effects of pioglitazone and metformin in preventing ischemic injury were studied. The hearts were divided into 4 experimental groups: the control (C) group, the P group consisting of pioglitazone treatment, the P + L5 group consisting of pioglitazone treatment with L‐NAME (5 min before ischemia), the M group consisting of metformin treatment, and the M + L5 group consisting of metformin treatment with L‐NAME (5 min before ischemia).ResultsIn the first experiment, the decrease in adenosine triphosphate (ATP) during ischemia was significantly inhibited in the P group in comparison with the C group (P < 0.01). However, the decrease in ATP was not inhibited in the P + L5 group during ischemia. In contrast, in the P + L60 group, the decrease in ATP was not inhibited during a part of ischemia. In the next experiment, a comparison between the effects of pioglitazone and metformin in preventing ischemic injury was studied. As a result of administration of either pioglitazone or metformin, there was no difference between groups with and without L‐NAME.ConclusionThese results suggest that pioglitazone has a significant beneficial effect on improving the myocardial energy metabolism during ischemia. This cardioprotection may be dependent on nitric oxide (NO) synthase during ischemia more than preischemia. Furthermore, the present findings suggest that both pioglitazone and metformin have equal cardioprotective effects mediated by NO on myocardial ischemic injury in rabbits. Copyright © 2003 John Wiley & Sons, Ltd.
Assessment of insulin sensitivity in vivo in control and diabetic mice with a radioactive tracer of glucose transport: [125I]‐6‐deoxy‐6‐iodo‐D‐glucose
Authors: Perret P. , Ghezzi C. , Mathieu J. P. , Morin C. , Fagret D. 
Published: July 2003

AbstractBackgroundImpairment of insulin‐stimulated glucose transport is a characteristic of type 2 diabetes. A radioactive glucose analogue has been synthesized: [125I]‐6‐deoxy‐6‐iodo‐D‐glucose. Its biological behaviour in vitro is similar to that of 3‐O‐methyl‐D‐glucose, the reference tracer of glucose transport. The aim of the present study was to determine the ability of [125I]‐6‐deoxy‐6‐iodo‐D‐glucose to evaluate variations in glucose transport in vivo.MethodsBiodistributions of [125I]‐6‐deoxy‐6‐iodo‐D‐glucose were performed with or without exogenous insulin (iv injection of 1.5 IU/kg) in db/+ non‐diabetic control mice and in db/db type 2 diabetic mice, exhibiting a severe insulin resistance characterized by a lack of increase in glucose uptake in response to insulin.ResultsIn db/+ mice, insulin increased [125I]‐6‐deoxy‐6‐iodo‐D‐glucose transport by 30% in most insulin‐sensitive tissues (heart, diaphragm and skeletal muscle, p < 0.05) and had no effect in other organs. In db/db mice, [125I]‐6‐deoxy‐6‐iodo‐D‐glucose transport in these organs was not modified by insulin.Conclusion[125I]‐6‐deoxy‐6‐iodo‐D‐glucose is able to trace in vivo an increase in glucose transport with insulin in non‐diabetic mice and a defect of glucose transport in type 2 diabetic mice. It is the first time that an iodinated analogue of glucose has shown such promising results after in vivo injection. The use of this tracer to assess glucose transport in vivo in humans via nuclear imaging warrants further investigation. Copyright © 2003 John Wiley & Sons, Ltd.
Early cell‐specific changes in nitric oxide synthases, reactive nitrogen species formation, and ubiquitinylation during diabetes‐related bladder remodeling
Authors: Poladia Deepali Pitre , Bauer John Anthony 
Published: July 2003

AbstractBackgroundUrinary bladder dysfunction in diabetes is a well‐recognized phenomenon but the mechanisms involved and initiating events are not clear. The physiological production of nitric oxide (NO) plays an important role in bladder tone and local immune defense, and recent studies have shown that NO‐derived reactive nitrogen species occur in many settings of chronic disease, including other diabetic complications. Here, we investigated the early time‐dependent and cell‐specific changes in the nitric oxide synthase isoforms (NOS1, 2, and 3), peroxynitrite, and ubiquitinylation in the well‐documented streptozotocin‐induced rat model of diabetes.MethodsImmunohistochemical methods and automated digital imaging were used for the measurement of morphometric and histochemical analysis of the bladder tissue regions. Region‐specific 3‐nitrotyrosine (a biomarker of NO dysregulation and reactive nitrogen species formation) and ubiquitinylated protein prevalence (marker of proteasomal activity) were also investigated.ResultsImmunohistochemistry revealed early, time‐dependent, and cell‐specific alterations in the three isoforms of NOS. We also observed region‐specific increases in protein nitration, demonstrating first‐time evidence of reactive nitrogen species formation in this setting. The changes in nitration did not pattern changes in NOS2 induction or tissue ubiquitinylation, and these alterations preceded any detectable changes in bladder structure (3 days vs 2 weeks) in this same animal preparation.ConclusionsThese data demonstrate that selective and regionally distinct changes in nitric oxide production and impaired nitric oxide control are early events during diabetic cystopathy and that mechanisms leading to increased oxidative stress and proteasomal activation may be key participants leading to organ dysfunction in this setting. Copyright © 2003 John Wiley & Sons, Ltd.
Diabetic atrial fibrillation patients: mortality and risk for stroke or embolism during a 10‐year follow‐up
Authors: Klem Igor , Wehinger Cornelius , Schneider Barbara , Hartl Elisabeth , Finsterer Josef , Stöllberger Claudia 
Published: July 2003

AbstractBackgroundTo compare in atrial fibrillation patients with and without diabetes, (1) baseline characteristics, (2) additional risk factors for stroke or peripheric or visceral embolism (hypertension, previous stroke, age >75 years), (3) mortality, (4) stroke or embolism, and (5) oral anticoagulation in the year 2000.MethodsIncluded were 409 outpatients with nonrheumatic atrial fibrillation (62 ± 12 years, 36% female). All underwent transthoracic and transesophageal echocardiography. Patients with thrombi received oral anticoagulation; patients without thrombi received aspirin until the follow‐up in 1995; afterwards, oral anticoagulation according to risk factors for stroke or embolism was recommended. Patients were contacted during the year 2000.ResultsType 2 diabetes was diagnosed in 73 patients (18%). Sixteen (22%) diabetic and 169 (50%) nondiabetic patients had no other risk factors for stroke or embolism (p < 0.0001). Diabetic patients were older, had more frequent heart failure, hypertension, myocardial infarction, left ventricular dysfunction, valvular abnormalities, left atrial or appendage thrombi, larger left atria, and left atrial appendages than nondiabetic patients. Mean follow‐up was 115 months. Diabetic patients had a higher mortality than nondiabetic patients (7%/year versus 4%/year, p < 0.0001). The rate of stroke or embolism of diabetic (3%/year) and nondiabetic patients (2%/year) was similar. The rate of oral anticoagulation was higher in diabetic than in nondiabetic patients (p = 0.0066).ConclusionsDiabetic patients with atrial fibrillation frequently have additional risk factors for stroke or embolism, and thus should be treated with oral anticoagulation. Whether in the rare cases of atrial fibrillation, in whom diabetes is the only clinical risk factor, oral anticoagulation is indicated cannot be answered by the present study. Copyright © 2003 John Wiley & Sons, Ltd.
Insulin secretion and action show differences in impaired fasting glucose and in impaired glucose tolerance in Asian Indians
Authors: Snehalatha C. , Ramachandran A. , Sivasankari S. , Satyavani K. , Vijay V. 
Published: July 2003

AbstractBackgroundThe aim of the study was to compare the abnormalities in insulin secretion and insulin sensitivity in impaired fasting glucose (IFG) and in impaired glucose tolerance (IGT).MethodsGlucose tolerance was determined by oral glucose tolerance test in 289 non‐diabetic subjects selected for this study (M : F, 160 : 129, mean age 42.2 ± 11.0 (SD) years, mean body mass index (BMI) 24.9 ± 4.2 kg/m2). Diabetic subjects were excluded from the study. The association of insulin resistance and β‐cell function (calculated by HOMA model) with IFG and IGT was studied using linear and multiple logistic regression analyses. Subjects with normoglycaemia (NGT) were used as controls.ResultsInsulin resistance was significantly more in IFG and in IGT than in NGT. β‐cell dysfunction was significantly higher in IFG than in IGT. IFG was associated with both insulin resistance (OR = 9.11, p < 0.001) and β‐cell dysfunction (inverse correlation, OR = 0.103, p < 0.001), while only insulin resistance was significantly associated with IGT (OR = 1.24, p = 0.005).ConclusionsIn urban South Asian Indians, IFG differed from IGT in having combined insulin resistance and β‐cell dysfunction, while IGT was associated only with insulin resistance. Copyright © 2003 John Wiley & Sons, Ltd.
Intermediate metabolism in normal pregnancy and in gestational diabetes
Authors: Di Cianni G. , Miccoli R. , Volpe L. , Lencioni C. , Del Prato S. 
Published: July 2003

AbstractComplex though integrated hormonal and metabolic changes characterize pregnancy. In the face of progressive decline in insulin action, glucose homeostasis is maintained through a compensatory increase in insulin secretion. This switches energy production from carbohydrates to lipids, making glucose readily available to the fetus. This precise and entangled hormonal and metabolic condition can, however, be disrupted and diabetic hyperglycemia can develop (gestational diabetes). The increase in plasma glucose level is believed to confer significant risk of complications to both the mother and the fetus and the newborn. Moreover, exposition of fetal tissues to the diabetic maternal environment can translate into an increased risk for development of diabetes and/or the metabolic syndrome in the adult life. In women with previous gestational diabetes, the risk of developing type 2 diabetes is greatly enhanced, to the point that GDM represents an early stage in the natural history of type 2 diabetes. In these women, accurate follow‐up and prevention strategies are needed to reduce the subsequent development of overt diabetes. This paper will review current knowledge on the modifications occurring in normal pregnancy, while outlining the mechanisms. In this paper, we will review the changes of intermediary metabolism occurring during pregnancy. In particular, we will outline the mechanisms responsible for gestational diabetes; the link between these alterations and associated maternal and neonatal morbidity will be examined. Copyright © 2003 John Wiley & Sons, Ltd.
The role of Lay Review Committees in diabetes research
Authors: Stenger David P. 
Published: July 2003

AbstractType 1 diabetes is unique among disease entities in having a large voluntary health nonprofit organization (the Juvenile Diabetes Research Foundation) that employs the process of review by laypersons (following a review by scientists) in selecting the recipients of its funding awards to individual investigators/trainees: grants, career‐development awards, fellowships, and ‘innovative grants.’ Therefore, that organization can be a suitable model on which an examination of lay review can be based. This paper summarizes (1) the history of how lay review originated and (2) this foundation's experience with it, (3) assesses the impact of the procedure on the discipline of diabetes science, and (4) examines the role it might play in the future, given the current state of that discipline. Copyright © 2003 John Wiley & Sons, Ltd.
Statin therapy for the treatment of diabetic dyslipidemia
Authors: Haffner Steven M. 
Published: July 2003

AbstractThe increasing prevalence of type 2 diabetes is a major problem for healthcare providers globally, since it is associated with serious microvascular and macrovascular complications. Although microvascular complications can be largely reduced with strict glycemic control, prevention of macrovascular disease involves a multifaceted approach that addresses all major risk factors, including dyslipidemia, hypertension, and insulin insensitivity. In particular, the treatment of diabetic dyslipidemia is a major challenge for diabetologists and cardiologists, as it is characterized by an array of lipid abnormalities. The management of diabetic dyslipidemia should initially include lifestyle approaches such as improved nutrition and weight reduction; however, the majority of patients require the addition of pharmacotherapy. Whilst insulin and/or oral hypoglycemic drugs are generally prescribed for the treatment of hyperglycemia, the addition of lipid‐lowering drugs may be necessary for the control of diabetic dyslipidemia. The American Diabetes Association guidelines recommend lowering of low‐density lipoprotein cholesterol (LDL‐C) as a first priority. Hydroxy‐methylglutaryl coenzyme A reductase inhibitors (statins) are recommended for first‐line therapy in diabetic patients, since these agents are effective at reducing LDL‐C levels. Whilst statins provide effective control of dyslipidemia in the majority of patients, more efficacious treatment regimens would provide greater benefit to more patients. Combination therapies may provide one solution to obtaining maximal lipid profile modifications, although the introduction of new, more efficacious agents for use as monotherapy may provide a more acceptable option, as drug combinations are often associated with poor tolerability and patient compliance. Copyright © 2003 John Wiley & Sons, Ltd.
Synthesis and Structure of New Macrocycles Including Spiro‐1,3‐Dioxane Units
Authors: Grosu Ion , Bogdan Elena , Plé Gérard , Toupet Loïc , Ramondenc Yvan , Condamine Eric , Peulon‐Agasse Valérie , Balog Mirela 
Published: July 2003

AbstractThe efficient synthesis of new macrocycles — “monomers” and “dimers” — containing spiro‐1,3‐dioxane units is reported. The structure of the compounds was determined from high‐field NMR spectra, FAB and MALDI+ mass spectrometry investigations. The solid‐state molecular structures of three compounds was determined. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Total Synthesis of Anhydromarasmone
Authors: Jauch Johann , Wallner Carsten , Herdtweck Eberhardt 
Published: July 2003

AbstractA synthesis of anhydromarasmone is presented using, as key step, an iridium‐catalyzed double‐bond isomerization from a homoallyl ether to an allyl ether. Other transition metal complexes employed for double‐bond transposition resulted in the vinyl ether as the final product. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Photoinduced Charge Separation in Cyclohexylidene‐Based Donor−(σ‐Bridge)−Acceptor Compounds − Building Blocks for Materials
Authors: Oosterbaan Wibren D. , van Gerven Paul C. M. , van Walree Cornelis A. , Koeberg Mattijs , Piet Jacob J. , Havenith Remco W. A. , Zwikker Jan W. , Jenneskens Leonardus W. , Gleiter Rolf 
Published: July 2003

AbstractWe describe the syntheses and properties of five semi‐rigid donor−(σ‐bridge)−acceptor (D−σ−A) compounds. These compounds, which are candidates for incorporation in materials, have aniline‐type donors and (mixed) cyano‐ and alkoxycarbonyl‐1,1‐difunctionalized vinyl acceptors that are separated by a four‐σ‐bond bridge. Their electronic properties were studied by means of photoelectron spectroscopy in combination with ab initio MO calculations, cyclic voltammetry, UV‐Vis absorption spectroscopy, (time‐resolved) fluorescence spectroscopy, and time‐resolved microwave conductivity (TRMC). We found that these D−σ−A compounds exhibit a weak intramolecular charge‐transfer absorption band that borrows its intensity from local transitions. Upon photoexcitation, a charge‐separated state is generated in virtually quantitative yield. Conformational contraction or “folding” of this state takes place for the two D−σ−A compounds with a dicyanovinyl acceptor in apolar solvents. The absence of folding in compounds with an alkoxycarbonyl‐functionalized acceptor is attributed to a reduced lifetime of the charge‐separated state. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Chemical Contributions to Understanding Heparin Activity: Synthesis of Related Sulfated Oligosaccharides
Authors: Poletti Laura , Lay Luigi 
Published: July 2003

AbstractHeparin and heparan sulfate are complex polysaccharides that modulate several biological events through the recognition of a number of distinct proteins. Chemical synthesis is a powerful tool to identify the unique binding domains responsible for the specific interactions and to generate potent analogues of the natural sequences. The present review reports the synthetic efforts of the last decade that are focused on the preparation of tailored fragments of these two polymers and analogues thereof. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Solid Phase Synthesis of Vancomycin Mimics
Authors: Arnusch Christopher J. , Pieters Roland J. 
Published: July 2003

AbstractA solid phase synthesis of a model system of the DE ring system of vancomycin is described. The synthesis involved biocatalytic resolutions of unnatural amino acids, is compatible with conventional solid phase peptide synthesis and contains as the key step: an on‐bead SNAr cyclization. Binding of a cyclic peptide to the carboxylate of N‐Ac‐D‐Ala was demonstrated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Studies of the Biogenesis of Verrucosins, Toxic Diterpenoid Glycerides of the Mediterranean Mollusc Doris verrucosa
Authors: Fontana Angelo , Tramice Annabella , Cutignano Adele , d’Ippolito Giuliana , Renzulli Licia , Cimino Guido 
Published: July 2003

AbstractThe biogenesis of verrucosins, diterpenoid glycerides of the marine mollusc Doris verrucosa, has been investigated by feeding experiments with labelled precursors. Incorporation of radioactive D‐[U‐14C]‐glucose into the diterpenes proved the de novo origin of verrucosins in the mollusc. Biogenesis of glycerol and terpenoid substructures has been investigated by feeding experiment with 13C‐labelled precursors. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Basicity and Solvatochromism of Concave Pyridines with Extended π‐Systems in Protic and Nonprotic Solvents
Authors: Storm Ole , Lüning Ulrich 
Published: July 2003

AbstractArylalkyne substituents have been connected to the 4‐positions of concave pyridines to give substituted concave pyridines 3, which possess absorption maxima above 300 nm in their UV spectra. Their protonation and their interaction with polar solvents have been studied. Firstly, with strong acids, protonation occurs, and relative basicities (logKass) have been determined. Substitution at the remote aryl ring influences the basicity of the pyridine, and Hammett plots show a linear relation between logKass and the electron density of the remote aryl ring. Secondly, concave pyridines 3 are capable of “sensing” hydrogen bonds between their pyridine nitrogen atom and an alcohol. Shifts of the absorption maxima to longer wavelengths are observed when certain quantities of alcohol are added. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis and UV/Vis Spectra of J‐Aggregating 5,5′,6,6′‐Tetrachlorobenzimidacarbocyanine Dyes for Artificial Light‐Harvesting Systems and for Asymmetrical Generation of Supramolecular Helices
Authors: Pawlik Andreas , Ouart André , Kirstein Stefan , Abraham Hans‐Werner , Daehne Siegfried 
Published: July 2003

AbstractA new class of dyes, in which the self‐assembling property of surfactants is combined with the capability for light energy propagation over long distances in dye J‐aggregates, is described. This has been achieved by the syntheses of achiral 5,5′,6,6′‐tetrachlorobenzimidacarbocyanine dyes 1, possessing systematically varied hydrophobic and hydrophilic substituents at their nitrogen atoms. These substituents are introduced into the 5,6‐dichlorobenzimidazole precursor 3 by substitution, either firstly by nucleophilic reaction with ψ‐bromoalkylnitriles and secondly by quaternization with alkyl bromides (route II) or firstly by nucleophilic reaction with alkyl bromides and secondly by quaternization with ψ‐bromoalkylnitriles or ψ‐bromoalkyl esters (route III) and subsequent saponification. The UV/Vis spectra of 20 differently substituted dyes containing the same chromophore 1 have been investigated. The spectra of the dye monomers in dimethyl sulfoxide are nearly identical, with no signs of optically activity, whereas in aqueous alkaline solutions quite different spectra are obtained for the dyes, indicating the formation of different aggregates depending on the nitrogen substituents. One of these types of J‐aggregate is optically inactive and displays a single red‐shifted (with respect to the dye monomers) absorption band, resembling the behaviour of J‐aggregates of common cyanine dyes. In the cases of strongly amphiphilic 5,5′,6,6′‐benzimidacarbocyanines 1 with 1,1′‐dialkyl substituents longer than hexyl and 3,3′‐bis(2‐carboxyethyl), 3,3′‐bis(3‐carboxypropyl) or 3,3′‐bis(3‐sulfopropyl) substituents, a new type of J‐aggregate is formed, and is distinguished by a doubly or even triply split J‐absorption band that displays optical activity. A third type of aggregate showing different spectral behaviour occurs when the dyes contain very short 3,3′‐bis(carboxymethyl) substituents or strongly hydrophobic fluorinated octyl groups, or when all four nitrogen atoms are identically substituted by hydrophilic 3‐carboxypropyl groups. The various types of dye aggregates have been characterized through UV/Vis spectroscopic parameters such as the positions and widths of the absorption and fluorescence bands, the Stokes′ shifts, the coupling constants, and the strength of the J‐band splitting. The results provide new prospects for the development of new artificial light‐harvesting systems as well as for the understanding of the evolution of asymmetry in the biosphere. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)