bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of metformin on the body composition in subjects with risk factors for type 2 diabetes
Authors: Rodríguez‐Moctezuma J. R. , Robles‐López G. , López‐Carmona J. M. , Gutiérrez‐Rosas M. J. 
Published: February 2005

Objectives:  To measure the effect of metformin on the body composition, insulin resistance and sensitivity in subjects with risk factors for type 2 diabetes mellitus (type 2 DM).Design:  Placebo‐controlled clinical trial.Material and methods:  Twenty‐three subjects with risk factors for type 2 DM were randomly assigned to receive 850 mg of metformin or a placebo twice a day for 2 months. Before and after the treatment, the body mass index and waist/hip ratio were calculated, the body composition was measured through bioelectric impedance and the fasting levels of blood glucose, insulin, triglycerides and cholesterol were measured. The level of insulin resistance was calculated by the homeostatic model and the level of sensitivity by the quantitative insulin sensitivity check index method. The Wilcoxon rank test was used.Results:  Twenty‐one subjects completed the study, 12 of the metformin group and nine of the placebo group. In the metformin group, there was a decrease in fat weight from 25.9 ± 9.4 to 20.8 ± 9.2 kg, p < 0.01, an increase in lean weight from 57.05 ± 13.6 to 61.9 ± 16.5 kg, p < 0.01, an increase in basal metabolism from 1735 ± 413 to 1878 ± 505 calories/day, p < 0.05 and an increase in body water, p < 0.05. There was no significant decrease in insulin resistance. In the placebo group, the blood glucose increased from 84.7 ± 13 to 96.7 ± 16 mg/dl, p < 0.05. There were no significant modifications in lipids.Conclusions:  The administration of metformin for 2 months improves the parameters of body composition and insulin dynamics in subjects with risk factors for type 2 DM.
Effects of a novel formulation of essential oils on glucose– insulin metabolism in diabetic and hypertensive rats: a pilot study
Authors: Talpur N. , Echard B. , Ingram C. , Bagchi D. , Preuss H. 
Published: February 2005

Background:  Insulin resistance and its most severe form type 2 diabetes mellitus are rapidly increasing throughout the world. It is generally recognized that natural products with a long history of safety can increase insulin sensitivity.Aims:  The present investigation examined the ability of various combinations of essential oils such as fenugreek, cinnamon, cumin, oregano, etc. to enhance insulin sensitivity. As a first approximation, we examined the effects of these natural products on Zucker fatty rats (ZFRs), a model of obesity and insulin resistance, and spontaneously hypertensive rats (SHRs), a model of genetic hypertension.Material and Methods:  Water or essential oils were given orally via droplets, and insulin sensitivity was estimated by systolic blood pressure (SBP) changes and circulating glucose and/or insulin concentrations.Results:  We have found that the ability to alter SBP in rat models is the most sensitive early index of insulin sensitivity. The combined essential oils lowered circulating glucose levels and SBP in both ZFRs and SHRs, suggesting that these natural products are enhancing insulin sensitivity. The second series of studies examined two additional combinations of essential oils along with the original formula. The major differences were in the types and proportions of individual oils contributing to a given formula.Conclusions:  Although all the three formulae decreased SBP in ZFRs, one of the formulae was more effective than the others in lowering circulating glucose in the glucose tolerance testing. Accordingly, some essential oils may be added to the long list of natural products that can affect insulin sensitivity.
The effect of multi‐factorial intervention on plasma von Willebrand factor, soluble E‐selectin and tissue factor in diabetes mellitus: implications for atherosclerotic vascular disease
Authors: Lim H. S. , Chong A. Y. , Freestone B. , Blann A. D. , Lip G. Y. H. 
Published: February 2005

AbstractBackground  Endothelial abnormalities and a hypercoagulable state may contribute to increased cardiovascular risk in diabetes mellitus, particularly in patients with overt cardiovascular disease (CVD). We sought to determine the effect of intensified multi‐factorial cardiovascular risk intervention on indices of endothelial abnormality and hypercoagulability in diabetes, and if patients with overt CVD would derive similar benefit as those without.Patients and methods  We measured plasma von Willebrand factor (vWf, an index of endothelial damage/dysfunction), soluble E‐selectin (sE‐sel, marking endothelial activation) and tissue factor (TF, an initiator of coagulation) by ELISA in 94 patients with diabetes mellitus (38 with CVD and 56 without overt CVD) and 34 comparable controls. Thirty‐three patients with CVD and 31 without overt CVD then participated in multi‐factorial cardiovascular risk intervention over 1 year.Results  Plasma levels of vWf (P = 0.009), sE‐sel (P < 0.001) and TF (P < 0.001) were significantly higher in diabetic patients compared with controls, with TF highest in patients with overt CVD. Intensive multi‐factorial intervention resulted in reductions in glycated haemoglobin (HbA1c), total and LDL‐cholesterol (all P < 0.05), but no significant weight change. This was associated with reductions in vWf in patients with (by 26%P = 0.003), and without (by 47%, P < 0.001), overt CVD. TF was reduced only in patients without overt CVD (by 45%, P < 0.001). There were no significant changes in sE‐sel levels in either group.Conclusion  Endothelial abnormalities in diabetes are only partially influenced by contemporary intensified multi‐factorial cardiovascular risk intervention. These data suggest the need for earlier and more aggressive risk factor intervention.
Renal damage in patients with Type 2 diabetes: a strong predictor of mortality
Authors: Bo S. , Ciccone G. , Rosato R. , Gancia R. , Grassi G. , Merletti F. , Pagano G. F. 
Published: February 2005

AbstractAims  (i) To compare mortality rates in a cohort of Type 2 diabetic patients with those of the general population; (ii) to assess the prognostic role of pre‐existing chronic conditions; (iii) to evaluate the impact of different severity of renal damage on mortality.Methods  All 3892 patients with Type 2 diabetes attending our Diabetic Clinic during 1995 and alive on 1 January 1996 were identified and followed for 4.5 years. Information on vital status (100% complete) and causes of death (98.5% complete) for 599 deceased subjects was derived from death certificates.Results  In comparison with the general population, standardized mortality ratios (× 100) were: 125 (95% confidence interval 104–148) in patients aged < 75 and 85 (75–95) in patients ≥ 75 years. Cardiovascular diseases and diabetes were responsible for most of the excess deaths. In a Cox‐proportional hazard model, renal damage was a powerful predictor of death (hazard ratio = 2.39; 95% confidence intervals = 2.00–2.85). The severity of renal damage was associated with increasing hazard ratios for death from all‐cause mortality and from specific causes (especially coronary artery disease, other cardiovascular causes and diabetes) after multiple adjustments. Other significant predictors of death were: greater age, glycated haemoglobin, smoking, lower body mass index, pre‐existing coronary and peripheral artery disease and known co‐morbidity (cirrhosis and cancer).Conclusions  Renal damage of any severity is significantly associated with subsequent mortality from all causes and from cardiovascular diseases. These associations are not confounded by pre‐existing co‐morbidity or coronary diseases.
Greater beneficial effects of visceral fat reduction compared with subcutaneous fat reduction on parameters of the metabolic syndrome: a study of weight reduction programmes in subjects with visceral and subcutaneous obesity
Authors: Park H. S. , Lee K. 
Published: February 2005

AbstractAims  To evaluate the effect of weight reduction on parameters of the metabolic syndrome in obese patients according to their pattern of abdominal fat distribution.Methods  A longitudinal intervention study, consisting of a 12‐week weight reduction programme, including lifestyle modification and adjuvant appetite suppressant, in 38 subjects with visceral obesity and 47 subjects with subcutaneous obesity. Visceral, subcutaneous and total adipose tissue areas were determined by CT scan at the level of L4–L5. Parameters for components of the metabolic syndrome were measured before and after weight reduction.Results  Reductions in body weight, BMI and subcutaneous adipose tissue area were greater in the subcutaneous than in the visceral obesity group. In contrast, changes in fasting plasma glucose, insulin, and HOMA score were higher in the visceral than in the subcutaneous obesity group. Changes in visceral adipose tissue area were significantly related to changes in fasting plasma glucose, triglycerides and HOMA score.Conclusions  Visceral fat reduction induced greater beneficial effects on parameters of the metabolic syndrome than subcutaneous fat reduction. Evaluation of changes in abdominal fat distribution is necessary when obese subjects enter a weight reduction programme.
Reduced plasma total homocysteine concentrations in Type 1 diabetes mellitus is determined by increased renal clearance
Authors: Veldman B. A. J. , Vervoort G. , Blom H. , Smits P. 
Published: February 2005

AbstractIntroduction  Elevated plasma levels of total homocysteine are related to the development of vascular complications. Patients with diabetes mellitus are particularly at risk for the development of these complications. Several factors determine plasma total homocysteine including renal function.Aims  As early Type 1 diabetes is characterized by a relative glomerular hyperfiltration, increased renal clearance could contribute to decreased levels of homocysteine as observed in Type 1 diabetes mellitus. Therefore we investigated the relationship between plasma total homocysteine and the glomerular filtration rate (GFR).Methods  In 92 Type 1 diabetes patients and 44 control subjects, we measured GFR and effective renal plasma flow (ERPF) by means of continuous infusion of inulin and p‐aminohippurate. Fasting plasma total homocysteine was measured using high performance liquid chromatography.Results  GFR (121 ± 21 resp. 104 ± 14 ml/min; P < 0.001) and ERPF (563 ± 127 resp. 516 ± 121 ml/min; P = 0.05) were significantly higher in Type 1 diabetes patients as compared with control subjects. Plasma total homocysteine was reduced in Type 1 diabetes patients as compared with control subjects (11.0 ± 4.5 resp. 13.4 ± 7 µmol/l; P = 0.01). Plasma total homocysteine was strongly correlated with GFR (Type 1 diabetes patients: r = −0.43, P < 0.001; control subjects: r = −0.39, P = 0.01).Conclusion  GFR is a major determinant of plasma total homocysteine levels in Type 1 diabetes patients as well as control subjects. The reduced plasma total homocysteine levels in diabetes patients can be explained by an increased GFR.
Foot temperature in diabetic polyneuropathy: innocent bystander or unrecognized accomplice?
Authors: Rutkove S. B. , Chapman K. M. , Acosta J. A. , Larrabee J. E. 
Published: February 2005

AbstractAim  To explore mechanisms by which temperature could influence the pathogenesis and symptoms of diabetic polyneuropathy.Methods  We conducted a literature review attempting to identify mechanisms by which diabetic polyneuropathy could be affected by temperature.Results  Cooling can theoretically hasten the progression of diabetic polyneuropathy through several different mechanisms. Specifically, cooling can enhance neuronal ischaemia, increase formation of reactive oxygen species, slow axonal transport, increase protein kinase C activity, and interfere with immune function. Short‐term temperature fluctuations (both warming and cooling) can initiate and exacerbate neuropathic pain by causing neuronal hyperexcitability and functional deafferentation. Although normal fluctuations of distal extremity temperature may be sufficient for these effects, impaired thermoregulation may make the distal extremities more susceptible to temperature extremes. Eventually, a ‘vicious cycle’ may ensue, resulting in neuronal deterioration with further disruption of temperature regulation. Limited epidemiological data suggest a higher prevalence of diabetic polyneuropathy in populations living in colder locations, supporting our hypothesis.Conclusions  Variations in foot temperature may play an important but as yet unrecognized role in the development and symptoms of diabetic polyneuropathy. Further basic and clinical research exploring this concept could help elucidate the natural history of diabetic polyneuropathy and lead to novel therapeutic strategies.
Maintenance tocolysis
Authors: Thornton James G. 
Published: February 2005

Background  Women who are undelivered after 48 hours of tocolysis remain at increased risk of preterm labour, but it is not clear whether prolonged treatment is effective.Objective  To review the current evidence for the effectiveness of maintenance tocolysis.Methods  The results of published systematic reviews were summarised.Results  Four systematic reviews and two trials published too recently for inclusion were identified. Maintenance tocolysis with β‐agonists and magnesium sulphate was ineffective in prolonging gestation or reducing any adverse fetal outcomes. One trial of maintenance tocolysis with nifedipine was underpowered to rule out an effect on prolonging gestation. One trial using the oxytocin receptor blocker, atosiban, showed that this drug used as maintenance tocolysis does prolong gestation, but the trial was too small to demonstrate any reduction in substantive fetal outcomes.Conclusions  There is insufficient evidence to justify the routine use of maintenance tocolysis in preterm labour. It remains plausible that prolongation of gestation might be beneficial in selected cases of very preterm labour where fetal compromise and infection have been ruled out. The only tocolytic that has been shown to prolong gestation when used as maintenance therapy is atosiban.
Control of death receptor and mitochondrial‐dependent apoptosis by c‐Jun N‐terminal kinase in hippocampal CA1 neurones following global transient ischaemia
Authors: Carboni Sonia , Antonsson Bruno , Gaillard Pascale , Gotteland Jean‐Pierre , Gillon Jean‐Yves , Vitte Pierre‐Alain 
Published: February 2005

Abstractc‐Jun N‐terminal kinase (JNK), a member of the mitogen‐activated protein kinase family, is activated in response to a number of extracellular stimuli, including inflammatory cytokines, UV irradiation and ischaemia. A large body of evidence supports a role for JNK signalling in stress‐induced apoptosis. It has been hypothesized that JNK may contribute to the apoptotic response by regulating the intrinsic cell death pathway involving the mitochondria. Here, we examined the role of the JNK signalling pathway in hippocampal CA1 apoptotic neurones following transient ischaemia in gerbils. We showed early activation of death receptor‐dependent apoptosis (caspase‐8 activation 2 days after ischaemia) and a biphasic activation of caspase‐3 and caspase‐9 after ischaemia. Activation of the mitochondrial pathway, as measured by cytochrome c release, appeared as a late event (5–7 days after ischaemia). AS601245, a novel JNK inhibitor, antagonized activation of both pathways and significantly protected CA1 neurones from cell death. Our results suggest a key role of JNK in the control of death receptor and mitochondrial‐dependent apoptosis after transient ischaemia.
Aph‐1 interacts at the cell surface with proteins in the active γ‐secretase complex and membrane‐tethered Notch
Authors: Hansson Emil M. , Strömberg Kia , Bergstedt Susanne , Yu Gang , Näslund Jan , Lundkvist Johan , Lendahl Urban 
Published: February 2005

AbstractThe activity of the γ‐secretase complex is critical for the processing of a number of transmembrane proteins, including Notch. Functional γ‐secretase activity can be reconstituted from four proteins – presenilin, nicastrin, Pen‐2 and Aph‐1 – but the role of the individual proteins remains unclear. In this report we describe the cellular localization and protein interactions of Aph‐1, with particular regard to Notch receptor processing. We found that Aph‐1 is present at the cell surface, where it interacts with Pen‐2, the mature forms of presenilin and nicastrin, and full‐length Notch. Aph‐1 also interacts with a truncated form of Notch, which is a direct substrate for γ‐secretase, but not with the Notch intracellular domain. Immunoprecipitation data for Notch and Aph‐1 showed that the Notch‐containing γ‐secretase complexes most likely form a small subset of the total number of γ‐secretase complexes. In conclusion, these data demonstrate that Aph‐1 is present at the cell surface, presumably in active γ‐secretase complexes, and interacts with the Notch receptor, both before and after ligand activation.
Monoamine transporter inhibitors and norepinephrine reduce dopamine‐dependent iron toxicity in cells derived from the substantia nigra
Authors: Paris Irmgard , Martinez‐Alvarado Pedro , Perez‐Pastene Carolina , Vieira Marcelo N. N. , Olea‐Azar Claudio , Raisman‐Vozari Rita , Cardenas Sergio , Graumann Rebeca , Caviedes Pablo , Segura‐Aguilar Juan 
Published: February 2005

AbstractThe role of dopamine in iron uptake into catecholaminergic neurons, and dopamine oxidation to aminochrome and its one‐electron reduction in iron‐mediated neurotoxicity, was studied in RCSN‐3 cells, which express both tyrosine hydroxylase and monoamine transporters. The mean ± SD uptake of 100 µm59FeCl3 in RCSN‐3 cells was 25 ± 4 pmol per min per mg, which increased to 28 ± 8 pmol per min per mg when complexed with dopamine (Fe(III)–dopamine). This uptake was inhibited by 2 µm nomifensine (43%p < 0.05), 100 µm imipramine (62%p < 0.01), 30 µm reboxetine (71%p < 0.01) and 2 mm dopamine (84%p < 0.01). The uptake of 59Fe–dopamine complex was Na+, Cl– and temperature dependent. No toxic effects in RCSN‐3 cells were observed when the cells were incubated with 100 µm FeCl3 alone or complexed with dopamine. However, 100 µm Fe(III)–dopamine in the presence of 100 µm dicoumarol, an inhibitor of DT‐diaphorase, induced toxicity (44% cell death; p < 0.001), which was inhibited by 2 µm nomifensine, 30 µm reboxetine and 2 mm norepinephrine. The neuroprotective action of norepinephrine can be explained by (1) its ability to form complexes with Fe3+, (2) the uptake of Fe–norepinephrine complex via the norepinephrine transporter and (3) lack of toxicity of the Fe–norepinephrine complex even when DT‐diaphorase is inhibited. These results support the proposed neuroprotective role of DT‐diaphorase and norepinephrine.
Process elongation of oligodendrocytes is promoted by the Kelch‐related actin‐binding protein Mayven
Authors: Jiang Shuxian , Avraham Hava Karsenty , Park Shin‐Young , Kim Tae‐Aug , Bu Xia , Seng Seyha , Avraham Shalom 
Published: February 2005

AbstractRearrangement of the cytoskeleton leading to the extension of cellular processes is essential for the myelination of axons by oligodendrocytes. We observed that the actin‐binding protein, Mayven, is expressed during all stages of the oligodendrocyte lineage, and that its expression is up‐regulated during oligodendrocyte differentiation. Mayven is localized in the cytoplasm and along the cell processes. Mayven also binds actin, and is involved in the cytoskeletal reorganization in oligodendrocyte precursor cells (O‐2A cells) that leads to process elongation. Mayven overexpression resulted in an increase in the process outgrowth of O‐2A cells and in the lengths of the processes, while microinjection of Mayven‐specific antibodies inhibited process extension in these cells. Furthermore, O‐2A cells transduced with recombinant retroviral sense Mayven (pMIG‐W‐Mayven) showed an increase in the number of oligodendrocyte processes with outgrowth, while recombinant retroviral antisense Mayven (pMIG‐W‐Mayven‐AS) blocked O‐2A process extension. Interestingly, co‐localization and association of Mayven with Fyn kinase were found in O‐2A cells, and these interactions were increased during the outgrowth of oligodendrocyte processes. This association was mediated via the SH3 domain ligand (a.a. 1–45) of Mayven and the SH3 domain of Fyn, suggesting that Mayven may act as a linker to bind Fyn, via its N‐terminus. Thus, Mayven plays a role in the dynamics of cytoskeletal rearrangement leading to the process extension of oligodendrocytes.
Pharmacological properties of homomeric and heteromeric pannexin hemichannels expressed in Xenopus oocytes
Authors: Bruzzone Roberto , Barbe Michael T. , Jakob Nurith J. , Monyer Hannah 
Published: February 2005

AbstractSeveral new findings have emphasized the role of neuron‐specific gap junction proteins (connexins) and electrical synapses in processing sensory information and in synchronizing the activity of neuronal networks. We have recently shown that pannexins constitute an additional family of proteins that can form gap junction channels in a heterologous expression system and are also widely expressed in distinct neuronal populations in the brain, where they may represent a novel class of electrical synapses. In this study, we have exploited the hemichannel‐forming properties of pannexins to investigate their sensitivity to well‐known connexin blockers. By combining biochemical and electrophysiological approaches, we report here further evidence for the interaction of pannexin1 (Px1) with Px2 and demonstrate that the pharmacological sensitivity of heteromeric Px1/Px2 is similar to that of homomeric Px1 channels. In contrast to most connexins, both Px1 and Px1/Px2 hemichannels were not gated by external Ca2+. In addition, they exhibited a remarkable sensitivity to blockade by carbenoxolone (with an IC50 of ∼5 μm), whereas flufenamic acid exerted only a modest inhibitory effect. The opposite was true in the case of connexin46 (Cx46), thus indicating that gap junction blockers are able to selectively modulate pannexin and connexin channels.
Inherited and acquired interactions between ACHE and PON1 polymorphisms modulate plasma acetylcholinesterase and paraoxonase activities
Authors: Bryk Boris , BenMoyal‐Segal Liat , Podoly Erez , Livnah Oded , Eisenkraft Arik , Luria Shai , Cohen Amir , Yehezkelli Yoav , Hourvitz Ariel , Soreq Hermona 
Published: February 2005

AbstractThe 5.5 Mb chromosome 7q21–22 ACHE/PON1 locus harbours the ACHE gene encoding the acetylcholine hydrolyzing, organophosphate (OP)‐inhibitable acetylcholinesterase protein and the paraoxonase gene PON1, yielding the OP‐hydrolyzing PON1 enzyme which also displays arylesterase activity. In search of inherited and acquired ACHE–PON1 interactions we genotyped seven polymorphic sites and determined the hydrolytic activities of the corresponding plasma enzymes and of the AChE‐homologous butyrylcholinesetrase (BChE) in 157 healthy Israelis. AChE, arylesterase, BChE and paraoxonase activities in plasma displayed 5.4‐, 6.5‐, 7.2‐ and 15.5‐fold variability, respectively, with genotype‐specific differences between carriers of distinct compound polymorphisms. AChE, BChE and arylesterase but not paraoxonase activity increased with age, depending on leucine at PON1 position 55. In contrast, carriers of PON1 M55 displayed decreased arylesterase activity independent of the − 108 promoter polymorphism. Predicted structural consequences of the PON1 L55M substitution demonstrated spatial shifts in adjacent residues. Molecular modelling showed substrate interactions with the enzyme variants, explaining the changes in substrate specificity induced by the Q192R substitution. Intriguingly, PON1, but not BChE or arylesterase, activities displayed inverse association with AChE activity. Our findings demonstrate that polymorphism(s) in the adjacent PON1 and ACHE genes affect each other's expression, predicting for carriers of biochemically debilitating ACHE/PON1 polymorphisms adverse genome–environment interactions.