Common carotid wall shear stress and carotid atherosclerosis in end-stage renal disease patients.

Decrease of arterial wall shear stress (WSS) is associated with higher probability of atherosclerotic plaque development in many disease conditions. End-stage renal diseases (ESRD) patients suffer from vascular disease frequently, but its nature differs from general population. This study was aimed at proving an association between common carotid wall shear stress and the presence of carotid bifurcation plaques in a group of ESRD patients. ESRD subjects, planned for the creation of a dialysis access and therapy were included. Wall shear rate (WSR) was used as a surrogate of WSS and was analyzed in the common carotid arteries by duplex ultrasonography. Intima media thickness (IMT) was measured at the same site. The presence/absence of carotid bifurcation plaques was recorded. The endothelial function was estimated by the levels of von Willebrand factor (vWf). 35 ESRD patients were included (19 females, 17 diabetics). Atherosclerotic plaque was present in 53 % of bifurcations. Wall shear rate was lower in arteries with plaques (349+/-148 vs. 506+/-206 s(-1), p=0.005) and was directly related to the height of IMT and inversely to the activity of vWf (r= -0.65, p=0.016). Lower wall shear rate in the common carotid arteries is linked to the endothelial dysfunction and to the presence of atherosclerotic plaques in carotid bifurcations in ESRD subjects. Faster arterial dilatation may facilitate this process in ESRD subjects.

Lower wall shear rate of the common carotid artery in treated type 2 diabetes mellitus with metabolic syndrome.

Arterial sites with low wall shear stress (WSS) are more prone to the development of atherosclerotic plaques, as was observed in carotid arteries in subjects with atherosclerosis risk factors. Type 2 diabetes mellitus (DM), hypertension, hyperlipidemia and other components of the metabolic syndrome, are associated with high risk for symptomatic cerebrovascular disease. It was shown by others that untreated type 2 DM is associated with lower WSS in common carotid arteries. However, the cardiovascular risk of type 2 DM could be modified by therapy. The aim of our study was to test the hypothesis that treated type 2 DM subjects with metabolic syndrome still have lower WSS in common carotid arteries than healthy controls. We enrolled 26 compensated DM subjects with metabolic syndrome, treated by metformin, statins and ACEI for more than 6 months, and 22 aged-comparable healthy controls. Wall shear rate (WSR) was used as a measure of WSS. A linear 3-11 MHz probe was used to measure blood velocity and internal diameter in the common carotid arteries. We compared observed values of WSR adjusted for age by ANCOVA. Wall shear rate was significantly lower in DM group than in control subjects: peak (systolic) values of wall shear rate were 410+/-130 s(-1) vs. 487+/-111 s(-1) (p<0.005). DM subjects had significantly lower WSR, because of both thinner lumen and slower blood flow velocities. Lower WSR was accompanied by higher IMT (0.73+/-0.12 mm vs. 0.64+/-0.11 mm, p<0.001). Treated subjects with compensated type 2 DM with metabolic syndrome still have atherogenic hemodynamic profile. These findings might help to understand faster progression of atherosclerosis in diabetic subjects with metabolic syndrome despite up-to-date medication.

Understanding the dialysis access steal syndrome. A review of the etiologies, diagnosis, prevention and treatment strategies.

Distal hypoperfusion ischemic syndrome (DHIS), commonly referred to as hand ischemia or 'steal' after dialysis access placement, occurs in 5-10% of cases when the brachial artery is used, or 10 times that of wrist arteriovenous fistulas (AVFs) using the radial artery. It is typically seen in elderly women with diabetes, and may carry severe morbidity including tissue or limb loss if not recognized and treated. Three distinct etiologies include (1) blood flow restriction to the hand from arterial occlusive disease either proximal or distal to the AV access anastomosis, (2) excess blood flow through the AV fistula conduit (true steal), and (3) lack of vascular (arterial) adaptation or collateral flow reserve (ie atherosclerosis) to the increased flow demand from the AV conduit. These three causes of steal may occur alone or in concert. The diagnosis of steal is based on an accurate history and physical examination and confirmed with tests including an arteriogram, duplex Doppler ultrasound (DDU) evaluation with finger pressures and waveform analysis. Treatment of steal includes observation of developing symptoms in mild cases. Balloon angioplasty is the appropriate intervention for an arterial stenosis. At least three distinct surgical corrective procedures exist to counteract the pathophysiology of steal. The ultimate treatment strategy depends on severity of symptoms, the extent of patient co-morbidity, and the local dialysis access technical team support and skills available.

Hyperlipidemia is associated with altered levels of insulin-like growth factor-I.

Previous studies revealed altered levels of the circulating insulin-like growth factor-I (IGF-I) and of its binding protein-3 (IGFBP-3) in subjects with coronary atherosclerosis, metabolic syndrome and premature atherosclerosis. Hyperlipidemia is a powerful risk factor of atherosclerosis. We expected IGF-I and IGFBP-3 alterations in subjects with moderate/severe hyperlipidemia but without any clinical manifestation of atherosclerosis. Total IGF-I and IGFBP-3 were assessed in 56 patients with mixed hyperlipidemia (MHL; cholesterol >6.0 mmol/l, triglycerides >2.0 mmol/l), in 33 patients with isolated hypercholesterolemia (IHC; cholesterol >6.0 mmol/l, triglycerides <2.0 mmol/l), and in 29 healthy controls (cholesterol<6.0 mmol/l, triglycerides<2.0 mmol/l). The molar ratio of IGF-I/IGFBP-3 was used as a measure of free IGF-I. IHC subjects differed from controls by lower total IGF-I (164+/-60 vs. 209+/-73 ng/ml, p=0.01) and IGF-I /IGFBP-3 ratio (0.14+/-0.05 vs. 0.17+/-0.04, p=0.04). Compared to controls, MHL subjects had lower total IGF-I (153+/-54 ng/ml, p=0.0002) and IGFBP-3 (2.8+/-0.6 mg/ml, p<0.0001), but higher IGF-I/IGFBP-3 ratio (0.25+/-0.06, p<0.0001). Differences remained significant after the adjustment for clinical and biochemical covariates, except for triglycerides. Patients with both IHC and MHL have lower total IGF-I compared to controls. The mechanism is presumably different in IHC and MHL. Because of prominent reduction of IGFBP-3 in patients with MHL, they have reduced total IGF-I despite the actual elevation IGF-I/IGFBP-3 ratio as a surrogate of free IGF-I.

[Wall shear stress in carotid artery and its role in the development of atherosclerosis]. / Smykové napetí v karotickém povodí a jeho role v rozvoji aterosklerózy.

Atherosclerosis is associated with systemic risk factors such as arterial hypertension, hyperlipidemia, diabetes mellitus and smoking. Yet it is a focal disease, predominantly affecting predisposed areas. The principal local hemodynamic factor is wall shear stress, i.e. the frictional force acting tangentially on the endothelial cell surface. The effect of wall shear stress on the endothelium depends on its magnitude and direction, as well as on the local vessel geometry and blood flow characteristics. Wall shear stress is an important determinant of endothelial function and phenotype. The article deals with the influence of wall shear stress on endothelial cell function, atherosclerotic plaque formation, and vascular remodelling in the common carotid artery.

Nuclear dynamics in Arabidopsis thaliana.

The nucleus is a definitive feature of eukaryotic cells, comprising twin bilamellar membranes, the inner and outer nuclear membranes, which separate the nucleoplasmic and cytoplasmic compartments. Nuclear pores, complex macromolecular assemblies that connect the two membranes, mediate communication between these compartments. To explore the morphology, topology, and dynamics of nuclei within living plant cells, we have developed a novel method of confocal laser scanning fluorescence microscopy under time-lapse conditions. This is used for the examination of the transgenic expression in Arabidopsis thaliana of a chimeric protein, comprising the GFP (Green-Fluorescent Protein of Aequorea victoria) translationally fused to an effective nuclear localization signal (NLS) and to beta-glucuronidase (GUS) from E. coli. This large protein is targeted to the nucleus and accumulates exclusively within the nucleoplasm. This article provides online access to movies that illustrate the remarkable and unusual properties displayed by the nuclei, including polymorphic shape changes and rapid, long-distance, intracellular movement. Movement is mediated by actin but not by tubulin; it therefore appears distinct from mechanisms of nuclear positioning and migration that have been reported for eukaryotes. The GFP-based assay is simple and of general applicability. It will be interesting to establish whether the novel type of dynamic behavior reported here, for higher plants, is observed in other eukaryotic organisms.

[Ossification of the posterior longitudinal ligament in the cervical spine]. / Osifikace ligamentum longitudinale posterius v krcní páteri.

Ossification of the ligamentum longitudinale posterius is a rare disease found in particular in Japan and southeastern Asia. In the literature it is described as the so-called Japanese disease or OPLL syndrome. The disease takes a slow, frequently asymptomatic, course but may cause severe stenosis of the spinal canal with neurological disorders, OPLL occurs frequently concurrently with ankylosing spondylitis, hypertrophic spondylosis, diffuse idiopathic hyperostosis of the skeleton. Own observation: a 68-year-old man with a long history of cervicalgia, subsequently paraesthesias of the upper extremities, without a spastic atactic symptomatology of the lower extremities. An X-ray extremities, of the skeleton was made, tomograms and CT of the cervical spine. In the Cl-6 area major ossifications of the posterior longitudinal ligament were found which caused stenosis of the spinal canal of an extent of up to two thirds.