Progressive leukoencephalopathy impairs neurobehavioral development in sialin-deficient mice.

Slc17a5 mice represent an animal model for the infantile form of sialic acid storage disease (SASD). We analyzed genetic and histological time-course expression of myelin and oligodendrocyte (OL) lineage markers in different parts of the CNS, and related this to postnatal neurobehavioral development in these mice. Sialin-deficient mice display a distinct spatiotemporal pattern of sialic acid storage, CNS hypomyelination and leukoencephalopathy.

Automated PGP9.5 immunofluorescence staining: a valuable tool in the assessment of small fiber neuropathy?

Background: In this study we explored the possibility of automating the PGP9.5 immunofluorescence staining assay for the diagnosis of small fiber neuropathy using skin punch biopsies. The laboratory developed test (LDT) was subjected to a validation strategy as required by good laboratory practice guidelines and compared to the well-established gold standard method approved by the European Federation of Neurological Societies (EFNS).

Asymptomatic small fiber neuropathy in diabetes mellitus: investigations with intraepidermal nerve fiber density, quantitative sensory testing and laser-evoked potentials.

This study aimed at evaluating the performance of a battery of morphological and functional tests for the assessment of small nerve fiber loss in asymptomatic diabetic neuropathy (DNP). Patients diagnosed for ≥10 years with type 1 (n = 10) or type 2 (n = 13) diabetes mellitus (DM) without conventional symptoms or signs of DNP were recruited and compared with healthy controls (n = 18) and patients with overt DNP (n = 5). Intraepidermal nerve fiber density (IENFd) was measured with PGP9.

The time course of CO2 laser-evoked responses and of skin nerve fibre markers after topical capsaicin in human volunteers.

Objective: To assess the temporal relationship between skin nerve denervation and regeneration (dermal and intra-epidermal fibres, IENF) and functional changes (CO(2) laser-evoked potentials, LEPs, and quantitative sensory tests, QST) after topical cutaneous application of capsaicin.

Methods: Capsaicin (0.075%) was applied to the lateral calf for three consecutive days.

Autophagy in cardiovascular disease.

Autophagy is a major cytoprotective pathway that eukaryotic cells use to degrade and recycle cytoplasmic contents. Recent evidence indicates that autophagy under baseline conditions represents an important homeostatic mechanism for the maintenance of normal cardiovascular function and morphology. By contrast, excessive induction of the autophagic process by environmental or intracellular stress has an important role in several types of cardiomyopathy by functioning as a death pathway.

Selective clearance of macrophages in atherosclerotic plaques by autophagy.

Objectives: The purpose of this study was to investigate whether stent-based delivery of an inhibitor of mammalian target of rapamycin (mTOR) can selectively clear macrophages in rabbit atherosclerotic plaques.

Background: Current pharmacologic approaches to stabilize atherosclerotic plaques have only partially reduced the incidence of acute coronary syndromes and sudden death. Macrophages play a pivotal role in plaque destabilization, whereas smooth muscle cells (SMC) promote plaque stability.

Autophagy as mechanism for cell death in degenerative aortic valve disease.

Once degenerative aortic valve disease becomes symptomatic, valve replacement is necessary for prognostic and symptomatic reasons. In elderly patients, symptoms of degenerative aortic valve can often be doubtful. Therefore, it is difficult but important to distinguish patients who need surgery from those who do not.

In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity.

Aims: Plaque rupture has been associated with a high matrix metalloproteinase (MMP) activity. Recently, regional temperature variations have been observed in atherosclerotic plaques in vivo and ascribed to the presence of macrophages. As macrophages are a major source of MMPs, we examined whether regional temperature changes are related to local MMP activity and macrophage accumulation.

Smooth muscle cell hypertrophy in varicose veins is associated with expression of estrogen receptor-beta.

Varicose veins are characterized by dilated and thickened vein walls. This study examined whether the changes that occur in varicose veins are associated with smooth muscle cell (SMC) hypertrophy, cellular proliferation or apoptosis. Moreover, the association between SMC hypertrophy and the expression of the estrogen receptor-beta (ERbeta) was investigated.

7-Ketocholesterol induces reversible cytochrome c release in smooth muscle cells in absence of mitochondrial swelling.

Objective: 7-Ketocholesterol, a major oxysterol in oxidized low-density lipoproteins in advanced atherosclerotic plaques, induces vascular smooth muscle cell (SMC) death. We investigated whether cytochrome c release participated in SMC death induced by 7-ketocholesterol and whether the processes were reversible.

Methods: SMC cultures derived from the rabbit aorta were exposed to 25 microM 7-ketocholesterol.

Intravascular thermography: Immediate functional and morphological vascular findings.

Aims: To investigate safety, feasibility, and injurious effect on endothelial cells of a thermography catheter as well as effect of flow on measured temperature in non-obstructive arteries.

Methods And Results: Safety and feasibility were tested in both rabbit aortas and pig coronary arteries. Evaluation of endothelial damage by the catheter (acute, 7 and 14 days) was performed in pig coronaries using Evans Blue, scanning electron microscopy (SEM) and Factor-VIII antibody and compared with normal arteries and arteries that underwent intravascular ultrasound (IVUS).

Nitric oxide donor molsidomine favors features of atherosclerotic plaque stability during cholesterol lowering in rabbits.

Rupture-prone atherosclerotic plaques are characterized by a thin fibrous cap containing numerous macrophage-derived foam cells and few smooth muscle cells (SMC). Decreasing the ratio between macrophages and SMC might favor plaque stabilization. Macrophages expressing inducible nitric oxide (NO) synthase become hypersensitive to killing by exogenous NO donors.

Augmentation of wall shear stress inhibits neointimal hyperplasia after stent implantation: inhibition through reduction of inflammation?

Background: Low wall shear stress (WSS) increases neointimal hyperplasia (NH) in vein grafts and stents. We studied the causal relationship between WSS and NH formation in stents by locally increasing WSS with a flow divider (Anti-Restenotic Diffuser, Endoart SA) placed in the center of the stent.

Methods And Results: In 9 rabbits fed a high-cholesterol diet for 2 months to induce endothelial dysfunction, 18 stents were implanted in the right and left external iliac arteries (1 stent per vessel).

Phagocytosis and macrophage activation associated with hemorrhagic microvessels in human atherosclerosis.

Objective: Previously, we demonstrated that activated inducible NO synthase (iNOS)-expressing foam cells in human carotid plaques often produce autofluorescent (per)oxidized lipids (ceroid). Here, we investigate whether intraplaque microvessels can provide foam cells with lipids and trigger macrophage activation.

Methods And Results: Microvessels (von Willebrand factor [vWf] immunoreactivity), activated macrophages (iNOS immunoreactivity), and ceroid were systematically mapped in longitudinal sections of 15 human carotid endarterectomy specimens.

Gene expression profiling of apoptosis-related genes in human atherosclerosis: upregulation of death-associated protein kinase.

Objective: Apoptosis substantially affects the cellularity and integrity of atherosclerotic plaques. It remains, however, unclear which key regulatory genes are involved. In this study, cDNA expression arrays were used to analyze transcript levels of 205 apoptosis-related genes in human carotid endarterectomy specimens versus nonatherosclerotic mammary arteries.

Deoxyribonucleic acid damage/repair proteins are elevated in the failing human myocardium due to idiopathic dilated cardiomyopathy.

Objectives: The study investigated the expression and relationship of deoxyribonucleic acid (DNA) repair enzymes with hemodynamic and nitric oxide (NO)-mediated stress in the failing myocardium.

Background: The role of apoptosis in human heart failure is controversial. Experimental studies suggested that NO-mediated stress modulates apoptosis of the cardiac myocytes.

A three-dimensional quantitative analysis of restenosis parameters after balloon angioplasty: comparison between semi-automatic computer-assisted planimetry and stereology.

Semi-automatic computer-assisted planimetry is often used for the quantification of restenosis parameters after balloon angioplasty although it is a time-consuming method. Moreover, slicing the artery to enable analysis of two-dimensional (2-D) images leads to a loss of information since the vessel structure is three-dimensional (3-D). Cavalieri's principle uses systematic random sampling allowing 3-D quantification.

Elevated levels of oxidative DNA damage and DNA repair enzymes in human atherosclerotic plaques.

Background: The formation of reactive oxygen species is a critical event in atherosclerosis because it promotes cell proliferation, hypertrophy, growth arrest, and/or apoptosis and oxidation of LDL. In the present study, we investigated whether reactive oxygen species-induced oxidative damage to DNA occurs in human atherosclerotic plaques and whether this is accompanied by the upregulation of DNA repair mechanisms.

Methods And Results: We observed increased immunoreactivity against the oxidative DNA damage marker 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) in plaques of the carotid artery compared with the adjacent inner media and nonatherosclerotic mammary arteries.

Platelet phagocytosis and processing of beta-amyloid precursor protein as a mechanism of macrophage activation in atherosclerosis.

In human occluded saphenous vein grafts, we previously demonstrated cytotoxic foam cells, presumably derived from macrophages engulfing platelets. In the present study, we investigated whether platelet phagocytosis occurs in human atherosclerotic plaques, whether this activates macrophages, and whether the platelet constituent, amyloid precursor protein (APP), was involved. Immunohistochemistry documented the presence of APP, beta-amyloid peptide (Abeta, cleaved from APP), and platelets (CD9), along with inducible NO synthase (iNOS) and cyclooxygenase-2, two markers of macrophage activation, around microvessels in advanced human carotid artery plaques (n=18).

In vivo temperature heterogeneity of atherosclerotic plaques is determined by plaque composition.

Background: Temperature heterogeneity of atherosclerotic plaques has been associated with macrophage accumulation in ex vivo studies. We investigated in vivo whether modifying the cell composition of rabbit atherosclerotic plaques by dietary cholesterol lowering can influence temperature heterogeneity.

Methods And Results: Twenty New Zealand rabbits were randomized to either a normal (n=10) or cholesterol-rich (0.