Etude pharmacogénétique de la variabilité de la réponse à la morphine parentérale

CAEN-BU Médecine pharmacie (141182102) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

Mécanismes impliqués dans la régulation des MAP kinases par les récepteurs opioïdes delta

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

Trimethylamine N-oxide (TMAO) and indoxyl sulfate concentrations in patients with Alcohol Use Disorder

International audienceBackground: Trimethylamine N-oxide (TMAO) and indoxyl sulfate (IS) are produced by the microbiota and the liver, and can contribute to brain aging and impaired cognitive function. This study aims to examine serum TMAO and IS concentrations in patients with alcohol-use disorder (AUD) at the entry for alcohol withdrawal, and the relationships with several biological, neuropsychological, and clinical parameters. Methods: TMAO and IS were quantified in thirty AUD inpatients and fifteen healthy controls (HC). The severities of AUD and alcohol withdrawal syndrome (AWS), and general cognitive abilities were assessed in AUD patients. Results: TMAO concentrations did not differ between HC and AUD patients. Several biomarkers assessing nutritional status and liver function were significantly different in AUD patients with the lowest TMAO concentrations compared to other AUD patients. IS concentration was significantly lower in AUD patients and a significant positive predictor of serum prealbumin variation during the acute phase of alcohol withdrawal. No relationship was observed between the concentrations of these metabo-23 lites and the severities of alcohol dependence, AWS, or cognitive deficits. Conclusions: Our data 24 suggest that AUD patients with low concentrations of TMAO or IS should probably benefit from a 25 personalized refeeding program during the acute phase of alcohol withdrawal

Thiamine and phosphate esters concentrations in whole blood and serum of patients with alcohol use disorder: a relation with cognitive deficits.

International audienc

Is plasma concentration of coenzyme Q10 a predictive marker for left ventricular remodelling after revascularization for ST-segment elevation myocardial infarction?

Background Left ventricular remodelling that frequently occurs after acute myocardial infarction is associated with an increased risk of heart failure and cardiovascular death. Although several risk factors have been identified, there is still no marker in clinical use to predict left ventricular remodelling. Plasma concentration of coenzyme Q10, which plays a key role in mitochondrial energy production and as an antioxidant, seems to be negatively correlated with left ventricular function after acute myocardial infarction. Objective The goal of our study was to determine whether the plasma coenzyme Q10 baseline concentrations at time of the ST-elevation myocardial infarction (STEMI) could predict left ventricular remodelling at six months' follow-up. Methods Sixty-eight patients who were admitted to hospital for STEMI and successfully revascularized with primary percutaneous coronary intervention were recruited. All patients underwent a 3D-echocardiography examination within the first four days after percutaneous coronary intervention and six months later then divided into two groups based on the presence or not of left ventricular remodelling. Plasma coenzyme Q10 concentration at the time of percutaneous coronary intervention was determined using high-performance liquid chromatography-tandem mass spectrometry. Results While we found similar plasma coenzyme Q10 concentrations compared with other studies, no association was evidenced between coenzyme Q10 concentrations and left ventricular remodelling (P = 0.89). Conclusion We found no evidence for using plasma coenzyme Q10 concentration as an early prediction marker of left ventricular remodelling after STEMI

Clinical and Biological Risk Factors for Neuropsychological Impairment in Alcohol Use Disorder.

The effects of alcoholism on cognitive and motor functioning are heterogeneous. While the role of some factors (patterns of alcohol consumption, eating habits or associated liver disease) has been hypothesized, the origins of this heterogeneity remain difficult to establish. The goals of the present study were thus to identify the clinical and biological risk factors for alcohol-related neuropsychological impairments and to determine the threshold beyond which these risk factors can be considered significant. Thirty alcoholic patients and 15 healthy controls had a blood test and underwent a neuropsychological examination. Alcohol severity measures, and liver, thiamine and malnutrition variables, were included in logistic regression models to determine the risk factors for cognitive and motor impairments (executive functions, visuospatial abilities, verbal episodic memory, ataxia), as well as those related to the severity of patients' overall neuropsychological profile (moderate or severe impairments). Liver fibrosis was found to be a risk factor for executive impairments and also for ataxia, when it was associated with long-term alcohol misuse and symptoms of withdrawal. Altered thiamine metabolism was solely predictive of verbal episodic memory impairments. This combination of biological abnormalities was associated with a profile of moderate neuropsychological impairments. Malnutrition was associated with a profile of more severe impairments. Malnutrition, altered liver function and thiamine metabolism explain, at least partially, the heterogeneity of alcohol-related neuropsychological impairments. Our findings could allow clinicians to identify patients at particular risk of severe neuropsychological impairments before the onset of irreversible and debilitating neurological complications

Hyperglycemia-Induced Hypovolemia Is Involved in Early Cardiac Magnetic Resonance Alterations in Streptozotocin-Induced Diabetic Mice: A Comparison with Furosemide-Induced Hypovolemia

<div><p>Aims</p><p>The aim of the study was to assess the early features of diabetic cardiomyopathy using cardiac magnetic resonance within the first week after streptozotocin injection in mice. We focused on the relationship between left ventricular function and hypovolemia markers in diabetic animals compared to a hypovolemic rodent model.</p><p>Methods and Results</p><p>Swiss mice were randomized into control (group C), streptozotocin-induced diabetes (group D) and furosemide-induced hypovolemia (group F) groups. Cardiac magnetic resonance, non-invasive blood pressure, urine volume, plasma markers of dehydration and cardiac histology were assessed in all groups. Mean blood glucose was higher in diabetic animals than in groups C and F (30.5±5.8 compared to 10.4±2.1 and 11.1±2.8 mmol/L, respectively; p<0.01). Diuresis was increased in animals from group D and F compared to C (14650±11499 and 1533±540 compared to 192±111 μL/24 h; p<0.05). End diastolic and end systolic volumes were lower in group D than in group C at week 1 (1.52±0.36 vs. 1.93±0.35 and 0.54±0.22 vs. 0.75±0.18 mL/kg, p<0.05). These left ventricular volume values in group D were comparable to those observed in the acute hypovolemia model (group F). Increased dehydration plasma markers and an absence of obvious intrinsic myocardial damage (evaluated by cardiac magnetic resonance and histology) suggest that a hemodynamic mechanism underlies the very early drop in left ventricular volumes in group D and provides a potential link to hyperglycemic osmotic diuresis.</p><p>Conclusions</p><p>Researchers using cardiac magnetic resonance in hyperglycemic rodent models should be aware of this hemodynamic mechanism, which may partially explain modifications in cardiac parameters in addition to diabetic myocardial damage.</p></div

CMR results at w1 and w4 in mice from groups C (control) and D (diabetes).

<p>CMR results at w1 and w4 in mice from groups C (control) and D (diabetes).</p

Clinical and biological results of mice from groups C, D and F.

<p>Clinical and biological results of mice from groups C, D and F.</p

Picro-Sirius red staining for fibrosis assessment of 6 μm myocardial slices from the basal third part of the heart of the mice from group C (control, left panel) and group D (diabetes, right panel).

<p>Picro-Sirius red staining for fibrosis assessment of 6 μm myocardial slices from the basal third part of the heart of the mice from group C (control, left panel) and group D (diabetes, right panel).</p