Treatment maintenance duration of dual therapy with metformin and sitagliptin in type 2 diabetes: The ODYSSEE observational study.

AIM: The study compared the duration of maintenance of treatment in patients with type 2 diabetes (T2D) using dual therapy with either metformin and sitagliptin (M-Sita) or metformin and a sulphonylurea (M-SU). MATERIALS AND METHODS: This observational study included adult patients with T2D who had responded inadequately to metformin monotherapy and therefore had started de-novo treatment with Met-Sita or Met-SU within the previous eight weeks. Patient follow-up and changes to treatment were performed according to their general practitioner's usual clinical practice. The primary outcome was time to change in treatment for whatever cause. HbA1c and symptomatic hypoglycaemia were also documented. RESULTS: The median treatment duration for patients in the M-Sita group (43.2 months) was significantly longer (P < 0.0001) than in the M-SU group (20.2 months). This difference persisted after adjusting for baseline differences and confounders. A similar reduction in HbA1c was noted in both arms (-0.6%), and the incidence of hypoglycaemia prior to treatment modification was lower with M-Sita (9.7%) than with M-SU (21.0%). Adverse events potentially related to treatment were reported in 2.8% (n = 52) and 2.7% (n = 20) of patients in the M-Sita and M-SU arms, respectively. CONCLUSION: Under everyday conditions of primary diabetes care, dual therapy with M-Sita can be maintained for longer than M-SU. In addition, while efficacy, as measured by changes in HbA1c, was similar between treatments, the incidence of hypoglycaemia was lower in patients taking M-Sita.

Type 2 diabetes mellitus in France in 2012: results from the ObEpi survey.

AIM: This analysis estimates the prevalence of type 2 diabetes mellitus (T2DM) in French adults participating in the ObEpi (obesity epidemiology) 2012 survey and also proposes a description of that population, according to comorbidities, treatments and sociodemographic factors related to the disease. METHODS: A self-administered questionnaire was posted to 20,000 households from the Kantar Health panel. In total, 25,714 adults aged≥18 years and representative of the French population completed the survey between January and March 2012. RESULTS: The prevalence of T2DM was 5.5±0.3% (95% CI) in this representative sample of the adult French population. Average age of patients was 65.9 years; 55% were men. Mean body mass index was 29.9kg/m(2) (men: 29.4kg/m(2), women: 30.6 kg/m(2); P<0.01); the prevalence of obesity was 43.1% (men: 39.9%, women: 47.1%; P<0.01). Patient-reported treatments for comorbidities were frequent: high blood pressure, 59.1%; dyslipidaemia, 59.9%; myocardial infarction/angina pectoris, 9.7%; revascularization, 7.8%; heart failure, 7.4%; sleep apnoea, 8.3%; and osteoarthritis, 10.7%. With regards to known treatments, 81.4% of patients were taking oral antidiabetic drugs (OADs), and 15.3% were using insulin therapy. Also, 18.8% of diabetic respondents reported financial hardship. CONCLUSION: T2DM remains a disease of major concern: compared with the non-diabetic population, all parameters surveyed showed unfavourable ratings, particularly for women.

Fish as a model in investigations about the relationship between oxygen consumption and hydroxyl radical production in permeabilized muscle fibers.

Mitochondrion is the main production site for reactive oxygen species (ROS). In endotherms, the existence of a positive relationship between ROS production and metabolic rate is acknowledged. But, little is known about ectotherms, especially fish, with a metabolic rate dependent on the environmental temperature. The maximal oxygen consumption and the production of highly reactive hydroxyl radicals by permeabilized red muscles of yellow and silver eels and trouts were measured concomitantly and compared to those of rats chosen for their comparable body mass, but different metabolic rate. The positive correlation found in fish between the metabolic rate and the ROS production showed a shift with respect to mammals.

Sex-related differences in aerobic capacities and reactive oxygen species metabolism in the silver eel.

Silver European eels (Anguilla anguilla L.) need to develop important aerobic capacities to cope with their long fasting spawning migration at depth, particularly males which are about half the size of females. Moreover, they have to face potential oxidative stress because reactive oxygen species (ROS) production is linked to the increase in metabolic rate. Thus, aerobic metabolism was globally evaluated in male and female silver eels exposed to a 10.1 MPa hydrostatic pressure (1,000 m depth). Oxygen consumption (MO(2)), ROS production and antioxidant enzyme activities were measured in the muscle fibres. Males showed a trend in both higher rate of aerobic metabolism and ROS production than females. After pressure exposure, ROS production was inversely correlated to metabolic rate only in males. By facilitating MO(2) rise with no harmful effects by ROS, the supposed enhanced aerobic capacities of males could speed up the sustained swimming. In females, the tendency to lower metabolic rate and higher catalase activity would make them less vulnerable to ROS effects. These results are in agreement with the hypothesis for different migration depths between genders.

Does hydrostatic pressure have an effect on reactive oxygen species in the eel?

Eels are submitted to hydrostatic pressure (HP) during their spawning migration (about 6000 Km). Before migration, they change from the yellow to the silver stage (silvering process). The effects of HP in relation to the silvering process have been studied on aerobic metabolism and more precisely on reactive oxygen species (ROS) metabolism. HP acclimatization of yellow eels improves oxidative phosphorylation together with supposed concomitant changes in electron leak and ROS production. Therefore hydroxyl radical (OH*) production, superoxyde dismutase and catalase activities, malondialdehyde content and in parallel oxygen consumption were measured in the red muscle of long-term pressure exposed and control group yellow and silver eels. At atmospheric pressure, yellow eels exhibited significantly higher oxygen consumption and OH* production than silver eels; and significantly lower malondialdehyde content. This could be due to the increase in membrane fluidity induced by the silvering process. Long-term HP exposure decreases yellow eel oxygen consumption which becomes similar to that of the silver stage. In parallel there is a decrease in OH* production and concomitantly antioxidant enzyme activities follow the same tendency. Thus the respiratory chain improvement in pressure acclimatized yellow eels is accompanied by a ROS production decrease which could mean an electron leak decrease.

A comparative study of reactive oxygen species in red muscle: pressure effects.

In ectotherms as well as in endotherms, the mitochondrial respiratory chain is the major source of reactive oxygen species (ROS) including the highly reactive, hydroxyl radical (OH*). It is known that the different steps involved in ROS production and the antioxidant systems are comparable in ectotherms and endotherms. But regulatory mechanisms in ROS production are less known especially in fish submitted to environmental changes. Firstly, we performed a ROS muscle metabolism interspecies study, using trout and eels as ectotherms and rats as endotherms, measuring OH* production, superoxide dismutase and catalase activities and in parallel oxygen consumption (MO2). Secondly, we studied the effects of an environmental factor (hydrostatic pressure) on ROS metabolism in both fish species. The results show that, at atmospheric pressure, fish have a higher OH*/MO2 ratio than rats which exhibit a higher superoxide dismutase activity. In fish exposed to hydrostatic pressure, this ratio is reversed so that for the same MO2 value, fish produce less OH* under hydrostatic pressure than at atmospheric pressure.

Hydrostatic pressure effects on eel mitochondrial functioning and membrane fluidity.

Aerobic metabolism which is required for long swimming activities during the eel's spawning migration at depth, is a potential target for pressure effects due to its components located in the inner mitochondrial membrane (respiratory chain and oxidative phosphorylation). Previous studies have evidenced that eels are able to acclimatize to pressure through membrane fluidity adjustment. However these studies were performed on the premigratory stage (yellow stage), which never encounters high pressure. Metamorphosis (silvering) seems to preadapt eels (at the silver stage) to most of the environmental changes they will encounter during migration. Is it also true for pressure resistance? This study shows that yellow eels exhibit a higher pressure sensitivity than silver eels (compression effects). The acclimatization period (21 days at 10.1 MPa) cancels the differences in pressure sensitivity and in aerobic metabolism observed at 0.1 MPa between the two stages. The mechanisms, which take place in yellow eels during acclimatization to high pressure, appear to be already present in silver eels before pressure exposure. Indeed at 0.1 MPa, silver eels exhibit higher membrane fluidity and proportions of membrane polyunsaturated fatty acids. Metamorphosis, by improving membrane fluidity, seems to allow silver eels to cope with hydrostatic pressure without spending energy in acclimatization processes.

Usefulness of fine needle aspiration cytology in the diagnosis of loco-regional recurrence of differentiated thyroid carcinoma.

AIM: The aim of our study was to define the usefulness of fine needle aspiration cytology (FNAC) in the assessment of loco-regional recurrence of differentiated thyroid carcinoma (DTC). METHODS: Among 1182 consecutive patients treated and followed for DTC from 1992 to 2001, we retrospectively analysed 65 FNAC results of patients presenting a suspicion of loco-regional recurrence. Recurrences were proved at histology in 35 cases and by cervical radioiodine uptake on post-therapeutic WBS (whole body scan) in nine cases. RESULTS: Among the 44 recurrences, FNAC results were malignant, benign and unsatisfactory in 33, two and nine cases, respectively. For the diagnosis of malignancy, FNAC sensitivity was 94%, specificity 100%, positive predictive value 100% and negative predictive value 87%. In the 35 cases where divergent results between diagnostic WBS (37-111MBq (131)I) and Tg level were observed, FNAC assessed the final status in 22 cases (malignant and benign in 17 and five cases, respectively). Of the 12 non-functioning and non-secreting lesions, FNAC diagnosed malignancy in four of the five malignant cases and ruled out malignancy in all seven benign lesions. CONCLUSION: These results outline the interest of FNAC in the assessment of loco-regional recurrences of DTC, especially when classical follow-up tools such as WBS and/or Tg level are unable to detect the recurrences.

[Insulin sensitivity, blood pressure and cardiovascular diseases]. / Insulinosensibilité, pression artérielle et maladies cardiovasculaires.

Essential hypertension is one of the main components of the insulin resistance syndrome. Blood pressure levels are especially critical for the cardiovascular prognosis of patients with diabetes. However, whether the relationship between blood pressure levels and insulin sensitivity is causal, or just an association, remains debatable. In this study, this relationship is explored through the data of currently available clinical trials.

Endovascular procedures under near-real-time magnetic resonance imaging guidance: an experimental feasibility study.

PURPOSE: The purpose of this study was to assess the feasibility of insertion of endovascular stents and the precision of an open-field interventional magnetic resonance imaging (iMRI) system in an in vivo model. METHODS: A feasibility study was undertaken at a university-affiliated hospital. Three male piglets with an average age of 6 months and a weight between 70 and 77 kg and two 3-month-old male piglets that weighed 40 to 44 kg were anesthetized. The five piglets underwent placement of nitinol stents inserted through the right femoral artery, under the guidance of a SIGNA-SP 0. 5T open-configuration iMRI unit. With a dedicated high-resolution near-real-time MRI sequence, the stent was guided and deployed onto a predefined target. RESULTS: The main outcome measures were the duration of the procedure from the beginning of positioning to the end of deployment of the stent, the final position of the stent in relation to the target on the iMRI screen, and comparison with autopsy findings. Three stents were deployed within the aorta at the level of the renal arteries, and two were deployed within the right iliac artery just below the aortic trifurcation. The average duration of the endovascular deployment was 13 minutes. There was an agreement of 0.6 mm in the position of the stent as observed on iMR images and found at autopsy. When the piglets were sacrificed, the average distance between the stents and the predefined target was 7. 8 mm, mostly because of the migration of one stent. Axial views allowed for accurate determination of stent impaction on the vascular wall. CONCLUSIONS: This study confirms the feasibility of stent deployment under near-real-time MRI guidance. It also emphasizes some inherent characteristics that hold promise with regard to other conventional techniques: stents and vascular structures are visualized in near-real-time in any desired plane, and the technique is performed without the potential adverse effects of ionizing radiations and iodinated contrast agents.

Regional brain bioamine levels under hyperbaric oxygen in two unequally susceptible strains of mice.

BACKGROUND: Hyperbaric oxygen (HBO) increases monoamine deamination with related toxic products which aggravates hyperbaric oxygen (HBO) neurotoxicity. However, the possibility of some protective action of monoamines balanced by the toxicity of their metabolites have received little attention. HYPOTHESIS: To try to unmask this protective action, we compared brain monoamine levels in two strains of mice differing in HBO-sensitivity and their sensitivity to HBO after norepinephrine (NE) depletion by N-(2-chloroethyl)-N-ethyl-2-bromo benzylamine (DSP4). METHODS: Mice were exposed to 6 ATA O2 for 90 min (C57 strain) and 24 min (HBO-sensitive CD1 strain) so that 50% of mice of each strain had preconvulsive symptoms when decompressed and 50%), had one generalized convulsion. After microwave sacrifice, monoamines in the cerebral cortex, the striatum and the brainstem were analyzed. Another series studied the effect of DSP4 on the delay to symptoms of these HBO)-exposed mice. RESULTS: NE normoxic levels in the striatum were greater in the HBO-sensitive CD1 than in the C57 strain. Under HBO, NE levels in the striatum and the cortex of CD1 fell without any concomitant increase in its metabolite whereas in the C57 strain, NE decreased less and its metabolite increased. There was no strain difference and little change in the NE levels in the brainstem. The increase in toxicity induced by DSP4 was highly significant in both strains; moreover C57 strain was more affected than CD1. CONCLUSION: Monoamine depletion before HBO aggravates HBO neurotoxicity. As monoamine deamination is known to be toxic, this demonstrates that monoaminergic activation is protective. The greater toxicity of DSP4 in the C57 strain suggests the involvement of monoamines in the strain-differential susceptibility to HBO. The lower sensitivity of CD1 mice to DSP4 may be related to a combination of less NE activation under HBO that in C57 and greater activation of peroxidation and amino acids in CD1 sensitive strain.

In vitro evaluation of the accuracy of open-configuration MRI in endovascular techniques.

The purpose of this study was to determine the accuracy of an interventional magnetic resonance imaging (iMRI) system to position an endovascular catheter in an in vitro model that simulated an infrarenal aortic aneurysm. Adequate visualization of abdominal aortic aneurysms (AAAs) was shown previously in humans. A dedicated near-real-time imaging protocol readily available on a Signa SP 0.5T open configuration MRI unit (General Electric Medical Systems, Milwaukee, WI, USA) was used to image the AAAs of ten human volunteers. A pulsatile in vitro model that simulated an AAA was built, which included the kidneys, the renal arteries, the aorta, and the iliac arteries. A catheter was advanced to a predetermined target through one of the iliac limbs of the model. Using two different techniques, the accuracy with which an interventionist could position the endovascular catheter under the near-real-time guidance of the iMRI system was evaluated. The AAAs of all ten patients were visualized, including the aneurysm wall, the thrombus within it, and the residual lumen, while maintaining adequate contrast, signal, and imaging speed. The position of the catheter was evaluated on target in 42 in vitro procedures. This series of tests showed an average accuracy of 1 mm for catheter positioning. The near-real-time imaging mode of the iMRI system enabled satisfactory evaluation of human AAAs, and it showed great accuracy for catheter positioning in the in vitro model. These results provide optimism regarding the potential of iMRI in endovascular surgery.

Changes in cerebrospinal fluid monoamine metabolites, tryptophan, and gamma-aminobutyric acid during the 1st year of life in normal infants. comparison with victims of sudden infant death syndrome.

Cerebrospinal fluid (CSF) levels of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, homovanillic acid, tryptophan, and gamma-aminobutyric acid were measured using high-performance liquid chromatography in 102 infants during the 1st year of life (preterm and term neonates included). CSF levels are expressed versus corrected age (postnatal days - preterm days) which reflects the stage of maturity of the central nervous system. These results are compared to those obtained in CSF of 53 victims of sudden infant death syndrome (SIDS). All components were significantly higher in SIDS than in the age-matched control group. This increase does not seem to be an artefact related to death. Indeed, under the same conditions concerning postmortem time interval before CSF sampling and analysis, the levels are not significantly higher in infants who died from a known pathology than in living infants. Moreover, in living infants as regards a pathology such as asphyxia or hypoventilation in comparison with SIDS, similar profiles are observed in some neurotransmitters or metabolites. Other studies are necessary to explore further neurotransmission systems in SIDS.

Simultaneous measurement of monoamines, their metabolites and 2,3- and 2,5-dihydroxybenzoates by high-performance liquid chromatography with electrochemical detection. Application to rat brain dialysates.

A reversed-phase chromatographic method with electrochemical detection was developed for the simultaneous determination of 2,3- and 2,5-dihydroxybenzoates, indicators of in vivo hydroxyl free radical formation, monoamines (NE, DA, 5-HT) and their metabolites (MHPG, DOPAC, HVA, 3MT, 5-HIAA). Linearity was observed from 10 pg to 10 ng injected. Reproducibility is correct (C.V. about 9%) except for 3MT and 5-HT. The limit of detection for almost all products was about 20 pg injected on the column. An application of this method in the study of the neurotoxicity of high pressure oxygen in rat is described. The limit of quantification for all compounds was 5 ng/ml except for HVA (10 ng/ml). Some basal levels DA, 5-HT, 5-HIAA, HVA, DOPAC, 3MT, 2,5-DHBA and 2,3-DHBA in microdialysates coming from striatum of normoxic restrained rats are given.

Amino acids and ammonia in the cerebral cortex, the corpus striatum and the brain stem of the mouse prior to the onset and after a seizure induced by hyperbaric oxygen.

The contents of amino acids (AA) and ammonia (NH3) were measured in corpus striatum, brain stem and cerebral cortex of two strains of mice exposed to hyperbaric oxygen (HBO). Mice of the HBO-sensitive strain (CD1) were exposed to 600 kPa O2 for 24 min versus 90 min for mice of the normal C57 strain, so that 50% of the mice in both strains developed a generalized convulsion. In the cortex of exposed but unconvulsed (EXUN) C57 mice, the contents of taurine, glutamine and NH3 increased while that of GABA decreased when compared to control mice. In the CD1 mice, NH3 content was increased while that of Asp decreased. After a convulsion, NH3 was increased in both strains, the AA contents returned to normal in C57 but Asp remained low in CD1 mice. Somewhat similar changes occurred in the striatum except that NH3 levels were less affected while GABA ones were significantly decreased in the CD1 mice exposed to HBO, whether convulsed or not. In the EXUN brain stem, Asp and Glu contents decreased. These decreases were greater in C57 on a percentage basis than in CD1 mice. GABA content was decreased in the C57 strain. After a convulsion, Asp and Glu levels remained low and NH3 accumulated in CD1 whereas in C57 only the Glu level was decreased. The cortical and striatal changes may indicate a lesser GABA supply in C57 strain and some Asp release in CD1 strain. In the brain stem of both strains, Asp and Glu release is possible in addition to GABA in C57 strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of one hyperbaric oxygen-induced convulsion on cortical polyamine content in two strains of mice.

In rat striatum, after one hyperbaric oxygen (HBO)-induced convulsion, polyamine changes are found that could promote N-methyl-D-aspartate (NMDA) activation. In the HBO-sensitive CD1 mouse, unlike in the common C57 strain, there is some support for NMDA activation after the HBO seizure. We measured PA cortical content before and after the first HBO-induced convulsion (about 608 kPa O2) in CD1 and C57 strains. Putrescine, spermidine and spermine were dansyl derived and analysed by HPLC. Exposure to HBO significantly increased putrescine content only in CD1 though a similar trend was observed in C57. No further increase was observed after convulsion whatever the strain. There were no significant changes in spermidine or spermine to support NMDA activation. Therefore, putrescine increase in CD1 cortex could reflect the free radical formation that is known to be greater in CD1 than in C57 mouse. Attempts to increase putrescine levels before HBO exposure hastened HBO-induced convulsion, less than spermidine or spermine. Because of physiological polyamine interconversion, additional experiments with indirect manipulation of putrescine levels and study of their time-course would precise these preliminary reports on putrescine and HBO.

Standardization in the determination of red blood cell polyamines by high-performance liquid chromatography.

The choice of the standardization method in the high-performance liquid chromatographic determination of dansyl polyamines (spermidine and spermine) in red blood cell extracts is discussed. 1,6-Hexanediamine, commonly used as an internal standard, is unsuitable for the quantification of spermidine and spermine in red blood cells because their percentage recoveries are significantly different (100% for 1,6-hexanediamine, and 70% for spermidine and spermine). The external standard method and the standard addition method are better suited. The procedure for the preparation of the standard mixture before dansylation has an influence on the values of red blood cell polyamines. Two procedures are compared and the corresponding percentages of variation were found to be high for spermidine and spermine. Thus the procedure in which the standard is treated in a strictly similar way as the red blood cells is certainly the most appropriate one for the quantification.

[Neurotransmission and sudden infant death. Study of cerebrospinal fluid]. / Neurotransmission et mort subite du nourrisson. Etude du liquide céphalo-rachidien.

The study of 33 cerebrospinal fluids of infants victims of sudden death shows a very significant increase of the metabolites of dopamine and serotonin. These determinations, compared to a control group, indicate a failure, concerning these two neurotransmitters, which could induce a cardiorespiratory seizure. This failure has likely a multifactorial origin.