Effects of Metabolic Risk Factors and Type 1 Diabetes on Brain Glucose and Brain Metabolites

The metabolic syndrome and type 1 diabetes are associated with brain alterations such as cognitive decline brain infarctions, atrophy, and white matter lesions. Despite the importance of these alterations, their pathomechanism is still poorly understood. This study was conducted to investigate brain glucose and metabolites in healthy individuals with an increased cardiovascular risk and in patients with type 1 diabetes in order to discover more information on the nature of the known brain alterations. We studied 43 20- to 45-year-old men. Study I compared two groups of non-diabetic men, one with an accumulation of cardiovascular risk factors and another without. Studies II to IV compared men with type 1 diabetes (duration of diabetes 6.7 ± 5.2 years, no microvascular complications) with non-diabetic men. Brain glucose, N-acetylaspartate (NAA), total creatine (tCr), choline, and myo-inositol (mI) were quantified with proton magnetic resonance spectroscopy in three cerebral regions: frontal cortex, frontal white matter, thalamus, and in cerebellar white matter. Data collection was performed for all participants during fasting glycemia and in a subgroup (Studies III and IV), also during a hyperglycemic clamp that increased plasma glucose concentration by 12 mmol/l. In non-diabetic men, the brain glucose concentration correlated linearly with plasma glucose concentration. The cardiovascular risk group (Study I) had a 13% higher plasma glucose concentration than the control group, but no difference in thalamic glucose content. The risk group thus had lower thalamic glucose content than expected. They also had 17% increased tCr (marker of oxidative metabolism). In the control group, tCr correlated with thalamic glucose content, but in the risk group, tCr correlated instead with fasting plasma glucose and 2-h plasma glucose concentration in the oral glucose tolerance test. Risk factors of the metabolic syndrome, most importantly insulin resistance, may thus influence brain metabolism. During fasting glycemia (Study II), regional variation in the cerebral glucose levels appeared in the non-diabetic subjects but not in those with diabetes. In diabetic patients, excess glucose had accumulated predominantly in the white matter where the metabolite alterations were also the most pronounced. Compared to the controls values, the white matter NAA (marker of neuronal metabolism) was 6% lower and mI (glia cell marker) 20% higher. Hyperglycemia is therefore a potent risk factor for diabetic brain disease and the metabolic brain alterations may appear even before any peripheral microvascular complications are detectable. During acute hyperglycemia (Study III), the increase in cerebral glucose content in the patients with type 1 diabetes was, dependent on brain region, between 1.1 and 2.0 mmol/l. An every-day hyperglycemic episode in a diabetic patient may therefore as much as double brain glucose concentration. While chronic hyperglycemia had led to accumulation of glucose in the white matter, acute hyperglycemia burdened predominantly the gray matter. Acute hyperglycemia also revealed that chronic fluctuation in blood glucose may be associated with alterations in glucose uptake or in metabolism in the thalamus. The cerebellar white matter appeared very differently from the cerebral (Study IV). In the non-diabetic men it contained twice as much glucose as the cerebrum. Diabetes had altered neither its glucose content nor the brain metabolites. The cerebellum seems therefore more resistant to the effects of hyperglycemia than is the cerebrum.

The effect of blood glucose on the vasculature in young patients with type 1 diabetes

Background. Patients with type 1 diabetes are at markedly increased risk of vascular complications. In this respect it is noteworthy that hyperglycaemia that is shown to cause endothelial dysfunction, has clearly been shown to be a risk factor for diabetic microvascular disease. However, the role of hyperglycaemia as a predictor of macrovascular disease is not as clear as for microvascular disease, although type 1 diabetes itself increases the risk of cardiovascular disease substantially. Furthermore, it is not known whether it is the short-term or the long-term hyperglycaemia that confers possible risk. In addition, the role of glucose variability as a predictor of complications is to a large extent unexplored. Interestingly, although hyperglycaemia increases the risk of pre-eclampsia in women with type 1 diabetes, it is unclear whether pre-eclampsia, a condition characterized by endothelial dysfunction, is also a risk factor for microvascular complication, diabetic nephropathy. Aims. This doctoral thesis investigated the role of acute hyperglycaemia and glucose variability on arterial stiffness and cardiac ventricular repolarisation in male patients with type 1 diabetes as well as in healthy male volunteers. The thesis also explored whether acute hyperglycaemia leads to an inflammatory response, endothelial dysfunction and oxidative stress. Finally, the role of pre-eclampsia, as a predictor of diabetic nephropathy in type 1 diabetes was examined. Subjects and methods. In order to study glucose variability and the daily glycaemic control, 22 male patients with type 1 diabetes, without any diabetic complications, were monitored for 72-h with a continuous glucose monitoring system. At the end of the 72-h glucose monitoring period a 2-h hyperglycaemic clamp was performed both in the patients with type 1 diabetes and in the 13 healthy age-matched male volunteers. Blood pressure, arterial stiffness and QT time were measured to detect vascular changes during acute hyperglycaemia. Blood samples were drawn at baseline (normoglycaemia) and during acute hyperglycaemia. In another patient sample, women with type 1 diabetes were followed during their pregnancy and restudied eleven years later to elucidate the role of pre-eclampsia and pregnancy-induced hypertension as potential risk factors for diabetic nephropathy. Results and conclusions. Acute hyperglycaemia increased arterial stiffness as well as caused a disturbance in the myocardial ventricular repolarisation, emphasizing the importance of a strict daily glycaemic control in male patients with type 1 diabetes. An inflammatory response was also observed during acute hyperglycaemia. Furthermore, a high mean daily blood glucose but not glucose variability per se is associated with arterial stiffness. While glucose variability in turn correlated with central blood pressure, the results suggest that the glucose metabolism is closely linked to the haemodynamic changes in male patients with uncomplicated type 1 diabetes. Notably, the results are not directly applicable to females. Finally, a history of a pre-eclamptic pregnancy, but not pregnancy-induced hypertension was associated with increased risk of diabetic nephropathy.

La norme du corps hybride : Une éthique de la reconstruction et de l'amélioration du corps humain en chirurgie

Aujourd'hui, techniques et technologies interagissent avec le corps humain et donnent aux personnes la possibilité de reconstruire leur corps, mais aussi de l'améliorer et de l'augmenter. L'hybridation est un processus technologique visant à compenser les défaillances humaines. L'augmentation de la puissance d'être est exaltée (santé, sexualité, performance, jeunesse), pourtant son accès n'est pas pour tous. Ce livre propose de démêler les différentes représentations du corps hybride et les projets qui les sous-tendent.

A new glucose: Towards conformationally locked flexoses through annulation

A new family of surf ace-modified carbohydrates with locked, axial-rich conformations and bipolarofacial architectures has been developed with the aid of carbocyclic ring annulation. These novel trans-decalin-based carbohydrates have been synthesized, from simple aromatic precursors such as tetralin, through the ozonolysis of an appropriately protected allylic alcohol, followed by a cascade of intramolecular acetalizations to generate the sugar pyran moiety. The stereoselective synthesis of (racemic) cyclohexane-annulated 0-glucopyranoside and a-glucofuranoside from a common annulated trans-cyclohexadiene diol (trans-CHD) precursor under-scores the versatility of our approach. The efficacy of the annulation stratagem in generating carbohydrate diversity has been demonstrated through the synthesis of two regioisomeric annulated gulose derivatives, which differ only in the site of ring annulation on the sugar moiety. The mapping of the MLP surface and solid-state architecture of the new sugar shows that cycloalkane annulation results in surface modification and fine-tuning of sugar hydrophilicity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).

A new glucose: Towards conformationally locked flexoses through annulation

A new family of surf ace-modified carbohydrates with locked, axial-rich conformations and bipolarofacial architectures has been developed with the aid of carbocyclic ring annulation. These novel trans-decalin-based carbohydrates have been synthesized, from simple aromatic precursors such as tetralin, through the ozonolysis of an appropriately protected allylic alcohol, followed by a cascade of intramolecular acetalizations to generate the sugar pyran moiety. The stereoselective synthesis of (racemic) cyclohexane-annulated 0-glucopyranoside and a-glucofuranoside from a common annulated trans-cyclohexadiene diol (trans-CHD) precursor under-scores the versatility of our approach. The efficacy of the annulation stratagem in generating carbohydrate diversity has been demonstrated through the synthesis of two regioisomeric annulated gulose derivatives, which differ only in the site of ring annulation on the sugar moiety. The mapping of the MLP surface and solid-state architecture of the new sugar shows that cycloalkane annulation results in surface modification and fine-tuning of sugar hydrophilicity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).

Glucose-Triggered Drug Delivery from Borate Mediated Layer-by-Layer Self-Assembly

In this study, we report a novel approach for glucose-triggered anticancer drug delivery from the self-assembly of neutral poly(vinyln alcohol) (PVA) and chitosan. In the present study, we have fabricated multilayer thin film of PVA-borate and chitosan on colloidal particle (MF particle) and monitored the layer-by-layer growth using Zetapotential measurements. Formation of multilayer membrane on MF particle has been further characterized with transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). Subsequently,disintegration of multilayer thin film and microcapsules was observed in presence of glucose. We investigated the disassembly of PVA-borate and chitosan self-assembly under CLSM and atomic force microscopy. These results suggest that this multilayer thin film is very efficient for encapsulation and release of DOX molecules above certain concentration of glucose (25 mM). This glucose-sensitive self-assembly is relevant for the application of anticancer therapeutic drug delivery.

Chloromycetin in the nutrition of the silkworm Bombyx mori L.-III. Influence on gut weight, oxygen uptake, and glucose absorption

Administration of chloromycetin has been found to enhance the oxygen uptake of the gut of the silkworm. The possibility that this increase might have been due to a thinning of the gut wall has been ruled out since the reduction in gut weight set in much later. Although glucose ultilization by the gut has been found to be increased in vitro, increase in oxygen uptake has not been affected in the presence of glucose. The possibility of a hormonal stimulation has been discussed.

Chloromycetin in the nutrition of the silkworm Bombyx mori L.-III. Influence on gut weight, oxygen uptake, and glucose absorption

Administration of chloromycetin has been found to enhance the oxygen uptake of the gut of the silkworm. The possibility that this increase might have been due to a thinning of the gut wall has been ruled out since the reduction in gut weight set in much later. Although glucose ultilization by the gut has been found to be increased in vitro, increase in oxygen uptake has not been affected in the presence of glucose. The possibility of a hormonal stimulation has been discussed.

Le Grand Tour Du reste de l’Europe jusqu’à la Laponie – et retour

Rencontre entre le Sud et le Nord Depuis des siècles, les pays méditerranéens ont entretenu des relations actives avec le Nord de l’Europe. Les regions du Nord ont été conquises et converties, manipulées et colonisées, mais aussi intégrées dans les réseaux commerciaux, scientifi ques, culturels et touristiques. Les voyageurs du Sud de l’Europe ont peu à peu découvert les regions plurielles du Nord de la Finlande, de la Suède, de la Norvège et de la presqu’île de Kola. L’attraction focntionnait aussi dans l’autre sens. Pour les gens du Nord, scientifi ques ou artistes, le Sud de l’Europe constituait une destination aussi exotique aue la Laponie pour ceux du Sud. Dans ce recueil, nous proposons dix points de vue sur ces échanges et réseaux entre la Sud et le Nord. Le premier chapitre présente Tornio, connue très tôt comme la porte de la Laponie, les premières relations scientifi ques entre le Nord et le Sud, ainsi que les exhibitions de Samis dans les métropoles européennes. Le deuxième chapitre propose une analyse des experiences et des impressions de voyageurs italiens, espagnols et français. Le dernier chapitre est consacré aux voyages d’artistes et écrivains fi nlandais en France, principalement à Paris. Ces rencontres entre le Sud et le Nord qui participèrent à la remise en cause, la relativisation et la construction des identities nationals et ethniques, permirent aussi de créer une conscience européenne commune.

Optimal Blood Glucose Regulation using Single Network Adaptive Critics

Diabetes is a serious disease during which the body's production and use of insulin is impaired, causing glucose concentration level toincrease in the bloodstream. Regulating blood glucose levels as close to normal as possible, leads to a substantial decrease in long term complications of diabetes. In this paper, an intelligent neural network on-line optimal feedback treatment strategy based on nonlinear optimal control theory is presented for the disease using subcutaneous treatment strategy. A simple mathematical model of the nonlinear dynamics of glucose and insulin interaction in the blood system is considered based on the Bergman's minimal model. A glucose infusion term representing the effect of glucose intake resulting from a meal is introduced into the model equations. The efficiency of the proposed controllers is shown taking random parameters and random initial conditions in presence of physical disturbances like food intake. A comparison study with linear quadratic regulator theory brings Out the advantages of the nonlinear control synthesis approach. Simulation results show that unlike linear optimal control, the proposed on-line continuous infusion strategy never leads to severe hypoglycemia problems.

Computer modelling approach to study the modes of binding of alpha- and beta-anomers of D-galactose, D-fucose and D-glucose to L-arabinose-binding protein

The modes of binding of alpha- and beta-anomers of D-galactose, D-fucose and D-glucose to L-arabinose-binding protein (ABP) have been studied by energy minimization using the low resolution (2.4 A) X-ray data of the protein. These studies suggest that these sugars preferentially bind in the alpha-form to ABP, unlike L-arabinose where both alpha- and beta-anomers bind almost equally. The best modes of binding of alpha- and beta-anomers of D-galactose and D-fucose differ slightly in the nature of the possible hydrogen bonds with the protein. The residues Arg 151 and Asn 232 of ABP from bidentate hydrogen bonds with both L-arabinose and D-galactose, but not with D-fucose or D-glucose. However in the case of L-arabinose, Arg 151 forms hydrogen bonds with the hydroxyl group at the C-4 atom and the ring oxygen, whereas in case of D-galactose it forms bonds with the hydroxyl groups at the C-4 and C-6 atoms of the pyranose ring. The calculated conformational energies also predict that D-galactose is a better inhibitor than D-fucose and D-glucose, in agreement with kinetic studies. The weak inhibitor D-glucose binds preferentially to one domain of ABP leading to the formation of a weaker complex. Thus these studies provide information about the most probable binding modes of these sugars and also provide a theoretical explanation for the observed differences in their binding affinities.

Simultaneous Utilization of Glucose and Sucrose by Thermophilic Fungi

The utilization of mixtures of glucose and sucrose at nonlimiting concentrations was studied in batch cultures of two common thermophilic fungi, Thermomyces lanuginosus and Penicilium duponti. The sucrose-utilizing enzymes (sucrose permease and invertase) in both fungi were inducible. Both sugars were used concurrently,regardless of their relative proportion in the mixture. At the optimal growth temperature (50C), T.lanuginosus utilized sucrose earlier than it did glucose, but at a suboptimal growth temperature (30°C) the two sugars were utilized at nearly comparable rates. The coutilization of the two sugars was most likely possible because (i) invertase was insensitive to catabolite repression by glucose, (ii) the activity and affinity of the glucose transport system were lowered when sucrose was included in the growth medium, and (iii) the activity of the glucose uptake system was also subject to repression by high concentrations of glucose itself. The concurrent utilization of the available carbon sources by thermophilic fungi might be an adaptive strategy for opportunistic growth in nature under conditions of low nutrient availability and thermal fluctuations in the environment.

Cohésion modale et subordination : Le conditionnel et le jussif finnois au miroir de la valeur sémantique et discursive du subjonctif français

Modal cohesion and subordination. The Finnish conditional and jussive moods in comparison to the French subjunctive This study examines verb moods in subordinate clauses in French and Finnish. The first part of the analysis deals with the syntax and semantics of the French subjunctive, mood occurring mostly in subordinate positions. The second part investigates Finnish verb moods. Although subordinate positions in Finnish grammar have no special finite verb form, certain uses of Finnish verb moods have been compared to those of subjunctives and conjunctives in other languages. The present study focuses on the subordinate uses of the Finnish conditional and jussive (i.e. the third person singular and plural of the imperative mood). The third part of the analysis discusses the functions of subordinate moods in contexts beyond complex sentences. The data used for the analysis include 1834 complex sentences gathered from newspapers, online discussion groups and blog texts, as well as audio-recorded interviews and conversations. The data thus consist of both written and oral texts as well as standard and non-standard variants. The analysis shows that the French subjunctive codes theoretical modality. The subjunctive does not determine the temporal and modal meaning of the event, but displays the event as virtual. In a complex sentence, the main clause determines the temporal and modal space within which the event coded by the subjunctive clause is interpreted. The subjunctive explicitly indicates that the space constructed in the main clause extends its scope over the subordinate clause. The subjunctive can therefore serve as a means for creating modal cohesion in the discourse. The Finnish conditional shares the function of making explicit the modal link between the components of a complex construction with the French subjunctive, but the two moods differ in their semantics. The conditional codes future time and can therefore occur only in non-factual or counterfactual contexts, whereas the event expressed by French subjunctive clauses can also be interpreted as realized. Such is the case when, for instance, generic and habitual meaning is involved. The Finnish jussive mood is used in a relatively limited number of subordinate clause types, but in these contexts its modal meaning is strikingly close to that of the French subjunctive. The permissive meaning, typical of the jussive in main clause positions, is modified in complex sentences so that it entails inter-clausal relation, namely concession. Like the French subjunctive, the jussive codes theoretical modal meaning with no implication of the truth value of the proposition. Finally, the analysis shows that verb moods mark modal cohesion, not only on the syntagmatic level (namely in complexe sentences), but also on the paradigmatic axis of discourse in order to create semantic links over entire segments of talk. In this study, the subjunctive thus appears, not as an empty category without function, as it is sometimes described, but as an open form that conveys the temporal and modal meanings emerging from the context.