Neurite density from magnetic resonance diffusion measurements at ultrahigh field: comparison with light microscopy and electron microscopy.

Due to its unique sensitivity to tissue microstructure, diffusion-weighted magnetic resonance imaging (MRI) has found many applications in clinical and fundamental science. With few exceptions, a more precise correspondence between physiological or biophysical properties and the obtained diffusion parameters remain uncertain due to lack of specificity. In this work, we address this problem by comparing diffusion parameters of a recently introduced model for water diffusion in brain matter to light microscopy and quantitative electron microscopy.

The application of stereological methods for estimating structural parameters in the human heart.

This study describes and exemplifies generally applicable design-based stereological methods for obtaining quantitative estimates of the numbers and sizes of capillaries, cardiomyocytes, and cardiomyocyte nuclei in immersion-fixed human left ventricles (N = 6). The design-based stereological methods are valid in all cardiac investigations onto quantifying changes in structure and function as seen under various conditions such as during development, aging, hypertrophy, and following ischemia/reperfusion. The applied principles of unbiased stereology were as follows: 1) uniform random sampling was taken at all levels, also in respect to orientations, for estimates of length and mean sizes.

The nodal location of metastases in melanoma sentinel lymph nodes.

Background: The design of melanoma sentinel lymph node (SLN) histologic protocols is based on the premise that most metastases are found in the central parts of the nodes, but the evidence for this belief has never been thoroughly tested.

Methods: The nodal location of melanoma metastases in 149 prospectively analyzed, completely step sectioned, positive SLNs from 96 patients was examined using 3 theoretical protocols, evaluating respectively: (1) the 3 most central step sections only; (2) the 3 most peripheral step sections only; and (3) 3 step sections evenly distributed throughout the individual SLNs. In addition, the size of the metastases located exclusively outside the 2 regional protocols (ie, 3 central sections, and 3 peripheral sections) were measured and compared with each other.

Metastatic melanoma volume in sentinel nodes: objective stereology-based measurement predicts disease recurrence and survival.

Aims: Sentinel lymph node (SLN) status is the most important prognostic factor in intermediate thickness melanoma. The amount of metastatic disease in positive SLNs varies greatly between patients, and this tumour burden appears to influence the prognosis of node-positive patients. The aim was to use objective stereological techniques to correlate accurately total SLN tumour burden with recurrence and patient survival.

Early neural and vascular dysfunctions in diabetic rats are largely sequelae of increased sorbitol oxidation.

These experiments were undertaken to assess the importance of cytoplasmic (c) sorbitol oxidation versus mitochondrial (m) pyruvate oxidation in mediating neural and vascular dysfunction attributable to hyperglycemia in diabetic rats. Increased oxidation of sorbitol is coupled to enzymatic reduction of free oxidized NAD(+)c to reduced NADHc, manifested by an increased ratio of NADH to NAD(+)c. Likewise, increased oxidation of pyruvate is coupled to reduction of NAD(+)m to NADHm, which increases the NADH/NAD(+)m ratio.

Atrophy and neuron loss: effects of a protein-deficient diet on sympathetic neurons.

Protein deficiency is one of the biggest public health problems in the world, accounting for about 30-40% of hospital admissions in developing countries. Nutritional deficiencies lead to alterations in the peripheral nervous system and in the digestive system. Most studies have focused on the effects of protein-deficient diets on the enteric neurons, but not on sympathetic ganglia, which supply extrinsic sympathetic input to the digestive system.

The developing left superior cervical ganglion of Pacas (Agouti paca).

In this study the main question investigated was the number and size of both binucleate and mononucleate superior cervical ganglion (SCG) neurons and, whether post-natal development would affect these parameters. Twenty left SCGs from 20 male pacas were used. Four different ages were investigated, that is newborn (4 days), young (45 days), adult (2 years), and aged animals (7 years).

Axonal plasticity elicits long-term changes in oligodendroglia and myelinated fibers.

Axons are linked to induction of myelination during development and to the maintenance of myelin and myelinated tracts in the adult CNS. Currently, it is unknown whether and how axonal plasticity in adult CNS impacts the myelinating cells and their precursors. In this article, we report that newly formed axonal sprouts are able to induce a protracted myelination response in adult CNS.

Naked siLNA-mediated gene silencing of lung bronchoepithelium EGFP expression after intravenous administration.

The use of systemic siRNA therapeutics for RNA interference-mediated silencing of disease genes is limited by serum instability and inadequate biodistribution. We have previously reported on the EGFP gene silencing effect of chitosan/siRNA nanoparticles in the bronchoepithelium of mice lungs following intranasal delivery and improved serum stability and reduced off-targeting effects in vitro by incorporation of locked nucleic acid (LNA). In this study, we examine the pulmonary gene silencing effect of siLNAs targeting enhanced-green-fluorescent-protein (EGFP) in lung bronchoepithelium upon intravenous delivery of naked siLNAs and upon intranasal delivery of either naked siLNA or chitosan/siLNA nanoparticles.

The effect of angiotensin II on the number of macula densa cells through the AT1 receptor.

The present study was performed to obtain information about a possible correlation between the activity of the renin-angiotensin system and the stereological features of the macula densa (MD). In normal kidneys, the numbers of angiotensin II AT1 receptors were estimated in MD cells and in the neighboring tubular cells. The total volumes of MD, MD cells, neighboring tubular cells, and the total number of MD cells, were measured in normal and candesartan-treated rats (15 mg/kg/day over 21 days).

Actinomyces naeslundii in initial dental biofilm formation.

The combined use of confocal laser scanning microscopy (CLSM) and fluorescent in situ hybridization (FISH) offers new opportunities for analysis of the spatial relationships and temporal changes of specific members of the microbiota of intact dental biofilms. The purpose of this study was to analyse the patterns of colonization and population dynamics of Actinomyces naeslundii compared to streptococci and other bacteria during the initial 48 h of biofilm formation in the oral cavity. Biofilms developed on standardized glass slabs mounted in intra-oral appliances worn by ten individuals for 6, 12, 24 and 48 h.

Serotonin transporter oligomerization documented in RN46A cells and neurons by sensitized acceptor emission FRET and fluorescence lifetime imaging microscopy.

The serotonin transporter is a member of the monoamine transporter family that also includes transporters of dopamine and norepinephrine. We have used sensitized acceptor emission fluorescence resonance energy transfer (FRET) and fluorescence lifetime imaging microscopy (FLIM) to study the oligomerization of SERT in HEK-MSR-239 cells, RN46A cells and in cultured hippocampal neurons. We were able to show identical FRET efficiencies in cell lines as well as in primary cultured hippocampal neurons, demonstrating that the oligomerization is cell type independent.

Demyelination induces the decline of the myelinated fiber length in aged rat white matter.

To determine the exact reason for the age-related decline of the myelinated fiber length in white matter, we performed this study. In middle-aged rats, there was age-related loss of the unmyelinated fibers with large diameters. The demyelination of the myelinated fibers with small diameters in middle-aged rat white matter might make the age-related decrease of the unmyelinated fibers with small diameters in the white matter unnoticeable.

Stage migration after minor changes in histologic estimation of tumor burden in sentinel lymph nodes: the protocol trap.

Background: Melanoma metastasis size estimates are of prognostic significance for groups of patients, but to the authors' knowledge, measurement consensus does not exist.

Methods: Maximum metastasis diameter, maximum centripetal tumor depth, microanatomic location of metastases, and complete metastasis volume were measured in 156 positive sentinel lymph nodes (SLNs) from 99 melanoma patients.

Results: The number of SLN-positive patients was increased by up to 41% using complete step-sectioning compared with less extensive protocols.

Intra-articular vs. systemic administration of etanercept in antigen-induced arthritis in the temporomandibular point. Part I: histological effects.

Background: Temporomandibular joint (TMJ) arthritis in children causes alterations in craniomandibular growth. This abnormal growth may be prevented by an early anti-inflammatory intervention. We have previously shown that intra-articular (IA) corticosteroid reduces TMJ inflammation, but causes concurrent mandibular growth inhibition in young rabbits.

Repeated electroconvulsive seizures increase the total number of synapses in adult male rat hippocampus.

The underlying mechanism of the therapeutic effect of electroconvulsive therapy (ECT) is still unclear. Here we investigated whether repeated electroconvulsive seizures (ECS), an animal model of ECT, in rats induce neuroplastic changes in the subregions of the hippocampus. ECS or sham treatment was given daily for 10 days to adult male rats.

A review of state-of-the-art stereology for better quantitative 3D morphology in cardiac research.

The aim of stereological methods in biomedical research is to obtain quantitative information about three-dimensional (3D) features of tissues, cells, or organelles from two-dimensional physical or optical sections. With immunogold labeling, stereology can even be used for the quantitative analysis of the distribution of molecules within tissues and cells. Nowadays, a large number of design-based stereological methods offer an efficient quantitative approach to intriguing questions in cardiac research, such as "Is there a significant loss of cardiomyocytes during progression from ventricular hypertrophy to heart failure?" or "Does a specific treatment reduce the degree of fibrosis in the heart?" Nevertheless, the use of stereological methods in cardiac research is rare.

Up- and down-regulation of angiotensin II AT1-A and AT1-B receptors in afferent and efferent rat kidney arterioles.

Introduction: The contractile effect of angiotensin II via AT1 receptors on the kidney arterioles is a crucial element in the kidney microcirculation. Angiotensin II also plays a role as an inhibitor via the AT1 receptors in the renin granulation of the arterioles. We have previously demonstrated that the AT1 receptors are downregulated in the renin-positive smooth muscle cells (SMCs) in contrast to renin-negative SMCs.

Application of stereological principles for quantification of bacteria in intact dental biofilms.

Introduction: Quantative confocal laser scanning microscopy (CLSM) in combination with fluorescent in situ hybridization (FISH) may help to increase our knowledge about biofilm formation. The purpose of this study was to develop and evaluate a stereological method for quantification of bacteria in intact biofilm. The method was applied in a quantitative study of the proportion of streptococci relative to other bacteria in initial in-situ-grown dental biofilms as a function of time.

Stereological estimates of alveolar number and size and capillary length and surface area in mice lungs.

The major function of the lung is gas exchange and depends on alveolar and capillary parameters such as surface area and volume. The number of alveoli may report on the nature of structural changes in lung parenchyma during development, illness or changing environmental factors. We therefore developed an efficient and easily applicable stereological design for estimating and monitoring these structural parameters in the mouse lung.

The association between renal function and structural parameters: a pig study.

Background: The objective was to investigate the association between renal structural parameters and renal function. The structural parameters were renal cortical volume, total renal volume, number of glomeruli, and total glomerular volume, and renal function was expressed by the single kidney GFR (skGFR). Investigations were performed using both healthy and chronically diseased kidneys.

The three-dimensional arrangement of the myocytes aggregated together within the mammalian ventricular myocardium.

Although myocardial architecture has been investigated extensively, as yet no evidence exists for the anatomic segregation of discrete myocardial pathways. We performed post-mortem diffusion tensor imaging on 14 pig hearts. Pathway tracking was done from 22 standardized voxel groups from within the left ventricle, the left ventricular papillary muscles, and the right ventricular outflow tract.

Asymmetric post-natal development of superior cervical ganglion of paca (Agouti paca).

Functional asymmetry has been reported in sympathetic ganglia. Although there are few studies reporting on body side-related morphoquantitative changes in sympathetic ganglion neurons, none of them have used design-based stereological methods to address this issue during post-natal development. We therefore aimed at detecting possible asymmetry-related effects on the quantitative structure of the superior cervical ganglion (SCG) from pacas during ageing, using very precise design-based stereological methods.