Longitudinal micro-ultrasound assessment of the ob/ob mouse model: evaluation of cardiovascular, renal and hepatic parameters.

BACKGROUND/OBJECTIVES: Obesity is reaching epidemic proportions and is associated with increased risk factors for cardiovascular disease. Leptin-deficient mice (ob/ob) are widely employed to investigate obesity. Aim of this study was to provide a micro-ultrasound (µUS) longitudinal evaluation of the ob/ob mouse model in terms of cardiovascular effects, consequences for renal microcirculation and liver fat accumulation. SUBJECTS/METHODS: Sixteen wild-type (wt) and eleven ob/ob male mice were studied at 8 (T0) and 25 (T1) weeks of age with a µUS system (Vevo2100) and B-mode and Doppler images were acquired. Cardiac output (CO), ejection fraction (EF), stroke volume (SV), fractional shortening (FS) and E/A ratio were measured from cardiac images. Mean diameter (Dmabd, Dmcar), relative distension (relDabd and relDcar) and pulse wave velocity (PWVabd and PWVcar) were obtained for both abdominal aorta and common carotid. As regards renal microcirculation, renal resistivity and pulsatility index (RI and PI) were assessed. The ratio between grey levels related to liver and kidney (Steato-Score) was used as index of hepatic steatosis. RESULTS: At T0, ob/ob mice showed reduced SV, EF, CO and relDabd values and increased LVmass, PWVabd, RI, PI and Steato-score measurements. The same comparison repeated at T1 highlighted similar results for SV, EF, CO, RI, PI and Steato-Score; furthermore, obese mice showed reduced Dmabd and Dmcar measurements in comparison with lean controls. The longitudinal analysis showed an increase in LVmass and Dmabd and a reduction of FS, EF, CO, relDabd and relDcar for wt animals, while no differences were found for the ob/ob group. CONCLUSIONS: ob/ob mice presented a premature cardiac dysfunction without a further age-related deterioration and a reduction in the abdominal aorta and carotid artery mean diameter in adult age. The proposed analysis can represent a valid approach for longitudinal studies aimed at testing new therapeutic strategies or for characterizing other mouse models.

Type 2 diabetes mellitus worsens arterial stiffness in hypertensive patients through endothelial dysfunction.

AIMS/HYPOTHESIS: Endothelium-derived factors are thought to be physiological modulators of large artery stiffness. The aim of the study was to investigate whether endothelial function could be a determinant of arterial stiffness in essential hypertensive patients, in relation with the concomitant presence of type 2 diabetes mellitus. METHODS: The study included 341 participants (84 hypertensive patients with and 175 without type 2 diabetes mellitus, 82 matched controls). Brachial artery endothelium-dependent flow-mediated dilation (FMD) was determined by high-resolution ultrasound and computerised edge detection system. Applanation tonometry was used to measure carotid-femoral pulse wave velocity (PWV). RESULTS: Hypertensive patients with diabetes had higher PWV (10.1 ± 2.3 m/s vs 8.6 ± 1.4 m/s, p < 0.001) and lower FMD (3.51 ± 2.07 vs 5.16 ± 2.96%, p < 0.001) than non-diabetic hypertensive patients, who showed impaired vascular function when compared with healthy participants (7.9 ± 1.6 m/s and 6.68 ± 3.67%). FMD was significantly and negatively correlated to PWV only in hypertensive diabetic patients (r = -0.456, p < 0.001), but not in hypertensive normoglycaemic patients (r = -0.088, p = 0.248) or in healthy participants (r = 0.008, p = 0.946). Multivariate analysis demonstrated that, in the diabetic group, FMD remained an independent predictor of PWV after adjustment for confounders (r(2) = 0.083, p = 0.003). Subgroup analysis performed in non-diabetic hypertensive patients revealed that neither obesity nor the metabolic syndrome affected the relationship between FMD and PWV. CONCLUSIONS/INTERPRETATION: Endothelial dysfunction is a determinant of aortic stiffness in hypertensive diabetic patients but not in hypertensive patients without diabetes. These results suggest that type 2 diabetes mellitus on top of hypertension might worsen arterial compliance by endothelium-related mechanisms.

Bilateral Gasser's ganglion sarcoidosis: diagnosis, treatment and unsolved questions.

Magnetic resonance imaging is currently the best means for confirming clinical suspicion of neurosarcoidosis as well as being useful in the follow-up of corticosteroid-treated patients. We report the case of a 34 year old male presenting suspected Heerfordt's syndrome with concentric facial hypesthesia. Mediastinal and parotid sarcoidosis was diagnosed and magnetic resonance imaging showed bilateral sarcoid involvement of Gasser's ganglion cisternae (such involvement was not revealed by computed tomography). The patient received corticosteroid therapy, with a clinical and radiological improvement. Magnetic resonance imaging showed disappearance of Gasser's ganglion lesions despite the persistence of mild facial hypesthesia. This case is noteworthy for its extremely rare lesion site. Post-treatment discrepancy between the clinical picture and imaging results is probably due to low MRI resolution threshold. 18-FDG positron emission tomography imaging might perhaps overcome the limits of magnetic resonance imaging.