Immunologic and inflammatory reactions to exogenous stem cells implications for experimental studies and clinical trials for myocardial repair

Intense research is under way to determine the optimal stem cell type and regimen for repairing diseased myocardium. Although initial studies in humans focused on the use of homologous stem cells, allogeneic or xenogeneic stem cells have been studied extensively in experimental work. Clinical trials with allogeneic stem cells are now under way, an approach based on the premise that stem cells and precursor cells are characterized as being immunotolerant. However, evidence indicates that stem cells may gain immune potency in vivo, especially when delivered to inflamed tissue, such as acutely infarcted myocardium. Histopathologic studies show the presence of a lymphohistiocytic inflammatory reaction at the sites of delivery of allogeneic stem cells, a response that is exaggerated with the use of xenogeneic stem cells. The immune-mediated inflammatory reaction to allogeneic and xenogeneic stem cells may elicit a spectrum of effects, ranging from beneficial (e.g., increased paracrine activity) to detrimental (e.g., accelerated damage and removal of stem cells). Although the issue of immune-mediated inflammatory responses to non-self stem cells requires further evaluation, non-self stem cells should not be considered as immunologically inert or exclusively immunosuppressive in vivo.     

Synthesis and pharmacological evaluation of a potent and selective σ1 receptor antagonist with high antiallodynic activity

Based on the pharmacophore model of Glennon the conformationally restricted σ(1) receptor ligand 2 with a 1,3-dioxane moiety has been designed and synthesized. The three step synthesis (transacetalization with pentane-1,3,5-triol, tosylation, and nucleophilic substitution with benzylamine) provided diastereoselectively the cis-configured 1,3-dioxane 2 in good yields. The 1,3-dioxane 2 represents a potent σ(1) receptor ligand (K(i) = 19 nM) with moderate selectivity over the σ(2) subtype (K(i) = 92 nM) and excellent selectivity against more than 60 other targets. Additionally the hERG K(+) channel is not affected by 2. In the capsaicin assay 2 showed extraordinarily high analgesic activity with more than 70% analgesia at the very low dose of 0.25 mg/kg body weight, which indicates σ(1) antagonistic activity. Since 2 does only interact with σ(1) receptors, the in-vivo antiallodynic activity of 2 must be attributed to the σ(1) antagonistic activity.     

Comprehensive model of care for highly specialized hospitals

In August 2007 the committee was installed to guide and direct medical management to the satisfaction and needs of medical equipment as special ingredient in the pursuit of quality health services that should be granted to the population.     

Three-dimensional isotropic wavelets for post-acquisitional extraction of latent images of atherosclerotic plaque components from micro-computed tomography of human coronary arteries

RATIONALE AND OBJECTIVES: The capability of wavelet transforms to separate signals into frequency bands is the basis for its use in image compression and storage, data management and transmission, and, recently, extraction of latent images of tissue components from noisy medical images. Analysis of temporal variations of radiofrequency backscatter of intravascular ultrasound with one-dimensional wavelets can detect lipid-laden plaque in coronary arteries with a sensitivity and specificity of >80%. In this study we evaluate the capability of a novel, 3-dimensional isotropic wavelet analysis to perform high resolution, non-directionally biased, statistically reliable, non-invasive discrimination between components of human coronary atherosclerotic plaques in micro-CT. MATERIALS AND METHODS: Coronary artery segments (5-15 mm) were excised at necropsy from 18 individuals with advanced coronary atherosclerosis. Specimens were imaged using a GE Locus SP ex vivo micro-CT scanner and processed for histological correlation (833 sections). The isotropic wavelet constructs were applied to the entire volume of CT data of each arterial segment to distinguish tissue textures of varying scales and intensities. Voxels were classified and plaque characterization achieved by comparing the relative magnitudes of these wavelet constituents to that of several reference plaque tissue components. RESULTS: Processing of micro-CT images via these isotropic wavelet algorithms permitted 3-D, color-coded, high resolution, digital discrimination between lumen, calcific deposits, lipid-rich deposits, and fibromuscular tissue providing detail not possible with conventional thresholding based on Hounsfield intensity units. Using the isotropic wavelets (with histology as the gold standard), lipid-rich pools approaching the size of the filter for the isotropic wavelet algorithm (0.25 mm [250 microns] in length) were identified with 81% sensitivity and 86% specificity. Calcific deposits, fibromuscular tissue, and lumen equal to or larger than the wavelet filter size were detected without error (100% sensitivity and specificity). CONCLUSION: Isotropic wavelet analysis permits high resolution, multi-dimensional identification of coronary atherosclerotic plaque components in micro-CT with sensitivity and specificity similar to that achieved with data obtained invasively (from IVUS in vivo) using one-dimensional wavelets. Further studies are necessary to test the applicability of this technology to clinical, multi-detector scanners.     

Male aging in the Middle Ages: commentaries on the book by Arnau de Vilanova "Conservatio juventute preservatio senectute"

In the Middle Ages medical texts the notes about personal hygiene are scarce and they are dedicated to the Kings or the aristocracy. In his work Regimen sanitatis ad inclytum regen Aragorum, Amaldo de Vilanova underlines six things that are necessary for cleanliness, among which he includes his well-known proposition Conservatio juventute preservatio senectute. We compared his text with those from other authors with references to the issue and, once examined, Vilanova's work stands out. Doctors in the middle ages were already interested in aging and propositions considered today as modern are found described in various works from that period.