Study of ventricular function by means of echocardiographic quantification of the thickness/radius (h/r) ratio of the left ventricle in healthy subjects

We studied 72 healthy subjects; 31 of them were adults and 41 children. By means of two-dimensional echocardiography we obtained a short axis view at the papillary muscle level of the ratio of the thickness (h) of the ventricular wall and the radius (r) of the cavity. We analysed ventricular performance determinants (pre-load, after-load and contractility). This non-invasive method gives information similar to pressure-volume curves. Thus, we propose it for the study of left ventricular overloads.     

High spectral and spatial resolution MRI of age‐related changes in murine prostate

The purpose of this work was to evaluate high‐resolution echo‐planar spectroscopic MRI of normal and precancerous prostatic changes in a transgenic mouse line. Simian virus large T‐antigen transgenic male mice (N = 7, age = 34 ± 3.7 weeks) with prostatic hyperplasia and intraepithelial neoplasia (PIN) were studied. High spectral and spatial resolution (HiSS) MRI of the water proton signal was compared to the free induction decay (FID) integral image and conventional gradient‐echo and spin‐echo imaging. Water peak‐height images of the prostate produced from HiSS datasets showed improved contrast‐to‐noise ratio (CNR) (P < 0.03), and greater morphological detail (P < 0.004) based on texture analysis. Despite the high spectral resolution of the HiSS datasets, signal‐to‐noise ratio (SNR) compared favorably with that of the FID integral and conventional images. Lobular features in HiSS images of older mice were consistent with hyperplasia seen on histology. A partially deuterated water‐filled catheter was inserted in the mouse rectum for susceptibility matching between the colon interior and exterior to minimize image artifacts. These preliminary results suggest that HiSS MRI provides detailed morphology of the murine prostate and can detect early changes associated with the development of cancer. HiSS MRI of patients may have similar advantages. Magn Reson Med 60:575–581, 2008. © 2008 Wiley‐Liss, Inc.     

Preclinical evaluation of illudins as anticancer agents

Illudins are low molecular weight natural products which were previously evaluated as anticancer drugs using rodent tumor models. In the present studies, we used in vitro cultures of human cancer cells to reevaluate their potential as anticancer agents. Using continuous exposure, Illudins S and M were cytotoxic to human leukemia cells at concentrations of 6-100 nM, but dihydroilludin M was 3 orders of magnitude less toxic, thus identifying a ketone site as a structural feature critical for cytotoxicity. Cytokinetic studies showed that illudin S caused a complete block at the G1-S phase interface of the cell cycle. Kinetics of inhibition of radiolabeled thymidine, uridine, and leucine incorporation suggested a primary effect on DNA synthesis. In colony and liquid culture assays, cell killing was time dependent but near maximal with a 2-h exposure. Myeloid and T-lymphocyte leukemia cells were most sensitive (50% inhibitory concentration, 6-11 nM), but B-cell leukemia/lymphoma, melanoma, and ovarian carcinoma cells were at least 10 times more resistant. Bone marrow granulocyte/macrophage progenitors showed intermediate sensitivity. Illudin S was equally effective against CEM T-lymphocyte leukemia cells expressing the multidrug resistance phenotype associated with Mr 180,000 glycoprotein and the parental cell line. CEM cells resistant to doxorubicin, epipodophyllotoxins, and 1-beta-D-arabinofuranosylcytosine showed only a 2-fold increased resistance to illudin S. Illudins are novel and potent cytotoxins which may be preferentially active against human myeloid and T-cell leukemias, including cells resistant to more conventional chemotherapeutic agents. The present studies illustrate the breadth of information which can be obtained on a new agent using present in vitro screening procedures and human cells.     

The role of amino phospholipids in the removal of the cito- and geno-toxic aldehydes produced during lipid oxidation.

The role of amino phospholipids in the removal of 4-hydroxy-2-alkenals and 4,5-epoxy-2-alkenals was studied to determine the fate of highly toxic oxygenated aldehydes produced in foods as a consequence of lipid oxidation. The results obtained showed that phosphatidylethanolamine rapidly removed both exogenously added aldehydes as well as the endogenously produced aldehydes when its fatty acid chains were oxidized in the presence of an oxidative stress inducer. This removal, which was always produced in the range of pH (6-9) and temperature (25-60 degrees C) studied, produced the corresponding carbonyl-amine reaction products between the aldehydes and the amino group of the amino phospholipid. These results suggest that, in the presence of amino phospholipids, the oxidation of polyunsaturated fatty acid chains is not likely to produce free oxygenated aldehydes in enough concentration to pose a significant risk for human health. On the other hand, these compounds contributed to the formation of specific carbonyl-amine reaction products whose toxicity is mostly unknown at present.     

Treatment of corneal chemical alkali burns with a crosslinked thiolated hyaluronic acid film

Purpose

The study objective was to test the utilization of a crosslinked, thiolated hyaluronic acid (CMHA-S) film for treating corneal chemical burns.

Are IL2 receptor antagonist useful in high risk acute tubular necrosis kidney recipients?

The questions are if old recipients from old donor have more incidence of delayed graft function and if antagonists of Il-2 receptors use decreased the incidence of NTA post-transplant. To answer the first question we have come to information from registry and uni or multicenter studies. We have used the Irish normograme that included 16 clinical questions from donors, recipients and kidney transplant. We concluded that age of donors increases likelihood of delayed graft function. The second question is answered in the literature with information of a meta-analysis with 38 clinical studies. Of them 9 (1.380 patients) studied delayed graft function and are against placebo. The odds ratio for delayed graft function was 0.87(IC 95% 0,72 a 1,06). Therefore, at the moment, we can conclude that the utilization of antagonists of Il-2 receptors does not have protective effect to NTA.