Content and traffic of taurine in hippocampal reactive astrocytes

Taurine is one of the most abundant free amino acids in the mammalian central nervous system, where it is crucial to proper development. Moreover, taurine acts as a neuroprotectant in various diseases; in epilepsy, for example, it has the capacity to reduce or abolish seizures. In the present study, taurine levels has been determine in mice treated with Kainic Acid (KA) and results showed an increase of this amino acid in hippocampus but not in whole brain after 3 and 7 days of KA treatment. This increase occurs when gliosis was observed. Moreover, taurine transporter (TAUT) was found in astrocytes 3 and 7 days after KA treatment, together with an increase in cysteine sulfinic acid decarboxylase (csd) mRNA, that codifies for the rate‐limiting enzyme of taurine synthesis, in the hippocampus at the same times after KA treatment. Glial cultures enriched in astrocytes were developed to demonstrate that these cells are responsible for changes in taurine levels after an injury to the brain. The cultures were treated with proinflammatory cytokines to reproduce gliosis. In this experimental model, an increase in the immunoreactivity of GFAP was observed, together with an increase in CSD and taurine levels. Moreover, an alteration in the taurine uptake‐release kinetics was detected in glial cells treated with cytokine. All data obtained indicate that astrocytes could play a key role in taurine level changes induced by neuronal damage. More studies are, therefore, needed to clarify the role taurine has in relation to neuronal death and repair. © 2010 Wiley‐Liss, Inc.     

Synthesis of 2-Fluoro N10-Substituted Acridones and Their Cytotoxicity Studies in Sensitive and Resistant Cancer Cell Lines and Their DNA Intercalation Studies

A series of 2-fluoro N¹⁰-substituted acridone derivatives with varying alkyl side chain length with propyl, butyl substitution, and a tertiary amine group at the terminal end of the alkyl side chain were synthesized and screened against cancer cell lines SW 1573, SW 1573 2R 160 (P-gp substrate) which are non-small lung cancer cell lines, MCF-7, MCF-7/MR (BCRP substrate) are breast cancer cell lines, 2008 WT, 2008MRP1, 2008MRP2, 2008MRP3 are ovarian cancer cell lines, and human embryo kidney cell lines like HEK293, HEK293 MRP4, and HEK293 MRP5i. The propyl-series compounds showed lipophilicity in the range of 1.93 to 4.40 and the butyl series in the range of 2.37 to 4.78. The compounds 4 , 7 , and 8 showed good cytotoxicity against the 60 human cancer cell line panel of the National Cancer Institute, USA. The compounds 14 and 15 showed a better cytotoxicity in most of the cancer cell lines compared to other compounds tested. The DNA-binding properties of the compounds were evaluated based on their affinity or intercalation with CT-DNA measured with absorption titration. The compound 11 bearing planar tricyclic ring linked with a butyl methylpiperazino side chain showed the highest binding affinity with a binding constant (K_i) of 10.38×10 M^–1. Evaluation of the compounds in cell lines with an overexpression of various multidrug resistance-related protein (MRP), P-glycoprotein (P-gp), or Breast Cancer Resistance Protein (BCRP) showed that all compounds are not substrates for any of these transporters.     

Reduction of G protein-coupled receptor kinase 2 expression in U-937 cells attenuates H2 histamine receptor desensitization and induces cell maturation

Histamine and H2 agonists transiently induce an important cAMP response in promonocytic U-937 cells but fail to induce monocytic differentiation because of a rapid receptor desensitization mediated by G protein-coupled receptor kinases (GRKs). The aims of the present study were to investigate the participation of GRK2 in the desensitization mechanism of the H2 receptor in U-937 cells by reducing GRK2 levels through antisense technology and to evaluate the differentiating capacity of cells expressing lower GRK2 level, stimulated by H2 agonists. By stable U-937 cell transfection with a GRK2-antisense cDNA, we obtained D5 and A2 cell clones exhibiting a reduction in GRK2 expression and an H3 clone with no significant difference in GRK2 expression from control cells. The cAMP response induced by the H2 agonist in D5 and A2 but not in H3 cells was higher than in U-937 and persisted for a longer period of time, although the number of H2 receptors in D5 and A2 cells was lower than in U-937. Furthermore, D5 and A2 cells treated with H2 agonist showed patterns of c-Fos and CD88 expression consistent with monocytic differentiated cells. Overall, these results indicate a direct correlation between the expression of GRK2 and the desensitization of natively expressed H2 receptors in U-937 cells, suggesting that GRK2 plays a major role in the regulation of these receptors' response. In turn, desensitization process is a key component of H2 receptor signaling, determining the differentiation capability of promonocytic cells.     

Left hemiparesis from atrial myxoma emboli

Atrial Myxomas are benign primary tumors of the heart, arising mainly from the left atrium. Clinical signs and symptoms produced by atrial myxomas may be non-specific or result in mechanical obstruction of cardiac function, arrhythmias, and embolization. The authors present a case of a 60-year-old woman who developed total left hemiparesis resulting from left atrial myxoma embolization causing complete occlusion of the right middle cerebral artery.     

Measuring quality of sedation in adult mechanically ventilated critically ill patients. the Vancouver Interaction and Calmness Scale. Sedation Focus Group

There are no reliable, valid, and responsive scales to measure the quality of sedation in adult critically ill patients. Our objective was to develop a summated rating scale with these properties and to define the minimal clinically important difference (MCID). We developed and tested the scale in an 18-bed medical-surgical intensive care unit (ICU) (12-bed acute and 6-bed subacute unit). Following identification of relevant domains and item derivation, 116 observations were made on 38 patients; psychometric properties and interrater reliability were assessed to allow item reduction. The final scale consisted of two five-item subscales quantifying calmness and interaction along a continuum from 5 to 30 points. Interrater reliability was 0.89 and 0.90; internal consistency was 0. 95 for both subscales. To test construct validity, MCID, and responsiveness 302 observations were made on 54 patients. Construct validity: calmness score vs. need for further intervention to make the patient calm (R = -0.82, P < 0.001); interaction score discriminated between acute vs. subacute units, mean scores 15.28 +/- 8.26 vs. 23.54 +/- 7.42, mean difference 8.27 (95% CI - 10.32 to -6.22); MCID - 2.2 and 2.5 for the calmness and interaction subscales; Guyatt's responsiveness statistics - 1.4 and 2.3. The Vancouver Interaction and Calmness Scale (VICS) is reliable, valid, and responsive.     

The beneficial effects of recipient-derived vascular endothelial growth factor on graft survival after kidney transplantation

BACKGROUND: Vascular endothelial growth factor (VEGF) is crucial for preservation of microvasculature and contributes to cytoprotection of the graft after kidney transplantation. METHODS: The authors investigated the influence of VEGF single-nucleotide polymorphism (SNP) on graft survival after renal transplantation. The SNP at positions -2578, -1154, and, -7 were analyzed in 306 donors and 387 recipients of renal transplants. RESULTS: The authors observed no effect of those recipient or donor SNP on acute rejection. However, graft survival was associated with recipient SNP at position -2578 C/A. Recipients with a genetic basis for high production of VEGF had significantly better graft survival compared with recipients with low production of VEGF. Homozygotes for the A allele (low producers of VEGF) had worse graft survival compared with high producers, the heterozygotes and homozygotes for C allele (P=0.03). Multivariate analysis in which the effects of donor age, recipient race, cold ischemia time, donor origin, and number of human leukocyte antigen mismatches were included showed that the status of noncarriers of -2578 C allele of recipients was an independent factor for graft failure (odds ratio, 1.8; 95% confidence interval, 1.0-3.0; P=0.03). CONCLUSIONS: The authors conclude that homozygote recipients for the -2578 A allele, the low producers of VEGF, are more vulnerable to tissue injury, resulting in worse graft survival.     

Squamous cell carcinoma in bladder extrophy

Bladder extrophy is a rare congenital malformation that nowadays is surgically corrected in neonatal period. We present a case report of a 71-year-old male with a verrucous squamous cell carcinoma arising in a classical uncorrected form of bladder extrophy.