Contribution of hypoxia-measuring molecular imaging techniques to radiotherapy planning and treatment

Hypoxia is related to poor prognosis because it is associated to chemo-and radioresistance. During recent years the evolution of imaging methods like PET/CT and MRI has meant the appearance of new perspectives with direct implications in radiation therapy. We discuss previous experiences in staging, planning and in the follow-up process with these techniques for measuring tumour hypoxia.     

Validation of a screening questionnaire for hip and knee osteoarthritis in old people

Background  

To develop a sensitive and specific screening tool for knee and hip osteoarthritis in the general population of elderly people.     

Elimination and minimization of the spherical aberration of intraocular lenses in high myopia

By applying Seidel aberration theory we have studied the spherical aberration of intraocular lenses in place ( S _IL), and the total spherical aberration of pseudophakic eyes ( S _IT). The optimum lens shapes for zero S _IL and S _IT or for minimum S _IL and S _IT of 12 schematic, highly myopic eyes were investigated. When the power required for emmetropization is positive, the total Seidel spherical aberration of the whole eye cannot be zero but can only be minimized. If the power of the intraocular lens is negative, the total Seidel spherical aberration of the whole eye can be made zero, and one of the optimum lens shapes would be meniscus with the convex surface towards the retina. In addition to improving the quality of the image, the lens has advantages from the physiological point of view, since it helps to maintain the structure of the eye.     

CD44 Isoform Expression Follows Two Alternative Splicing Pathways in Breast Tissue

The repertoire of distinct CD44 protein isoforms is generated by means of alternative pre-mRNA splicing of 10 variable exons located in the central region of the CD44 gene. We have used human breast ductal carcinoma as a model to identify two alternative splicing pathways of the CD44 pre-mRNA variable region that account for the generation of all of the CD44 isoforms described in breast tissue. An alternative splicing pathway that reflects inclusion of variable exons in a gradual 3′-to-5′ fashion is evidenced in breast ductal carcinoma and its lymph node metastases. This pathway is compatible with a mechanism that generates the standard form of CD44 (devoid of variable exons) and is distinguishable from an alternative splicing pathway that involves exclusively variant exon 3 and is observable in both normal and carcinoma breast tissue. We show that both pathways are detectable in the same cell type in the breast and provide a speculative model by which these splicing routes could take place.     

Noradrenergic and opioidergic alterations in neuropathy in different rat strains

The Fischer 344 (F344) rat strain differs from the Lewis strain in the response to neuropathic pain. Recently, we found that F344 rats totally recover from mechanical allodynia induced by chronic constriction injury (CCI) of the sciatic nerve 28 days after surgery whereas Lewis rats are initiating their recovery at this time point. Thus, the use of this neuropathic pain model in these different rat strains constitutes a good strategy to identify possible target genes involved in the development of neuropathic pain. Since differences between Lewis and F344 rats in their response to pain stimuli in acute pain models have been related to differences in the endogenous opioid and noradrenergic systems, we aimed to determine the levels of expression of key genes of both systems in the spinal cord and dorsal root ganglia (DRG) of both strains 28 days after CCI surgery. Real time RT-PCR revealed minimal changes in gene expression in the spinal cord after CCI despite the strain considered, but marked changes in DRG were observed. A significant upregulation of prodynorphin gene expression occurred only in injured DRG of F344 rats, the most resistant strain to neuropathic pain. In addition, we found a significant downregulation of tyrosine hydroxylase and proenkephalin gene expression levels in both strains whereas δ-opioid receptor was found to be significantly downregulated only in injured DRG of Lewis rats although the same trend was observed in F344 rats. The data strongly suggest that dynorphins could be involved in strain differences concerning CCI resistance.     

Glutathione-S-transferase P1 gene polymorphism and susceptibility to endometriosis

BACKGROUND: Glutathione-S-tranferase (GST) is the part of the key phase II detoxifying enzyme system. Many studies have investigated the role of GSTM1 and GSTT1 gene polymorphisms in endometriosis. Although GSTP1 was found to be one of the most abundant types of GST in genital system, there are insufficient data about the importance of the role of GSTP1 gene polymorphism in endometriosis. METHODS: This case-control study involved 150 patients with endometriosis and 150 controls. The frequency of GSTP1 single nucleotide polymorphisms was evaluated using PCR and melting curve analysis. RESULTS: The proportion of GSTP1 ile/ile tended to be higher in patients with endometriosis than control group, although the difference was not significant [odds ratio (OR)=1.53; 95% confidence interval (CI)=0.95-2.46]. In contrast, GSTP1 val/val was significantly higher in control patients and seems protective for endometriosis (OR=0.10; 95% CI=0.02-0.42). CONCLUSION: The results of this study suggest that GSTP1 polymorphism might modulate the risk of endometriosis with significantly decreased risk for GSTP1 val/val and marginally increased risk for GSTP1 ile/ile. Further studies on not only the disease processes but also normal distribution of the enzyme in female genital tract may provide better understanding about the role of GST types and their polymorphs in endometriosis.     

S-adenosyl-L-methionine prevents 5-HT(1A) receptors up-regulation induced by acute imipramine in the frontal cortex of the rat

S-adenosyl-L-methionine (SAM) has shown efficacy in speeding the onset of the antidepressant effect of imipramine in depressed patients. This effect may be related to their interactions at the serotonin(1A) (5-HT(1A)) receptors. Acute imipramine up-regulated the frontal cortex 5-HT(1A) receptors (B(max), 51.5 +/- 8.4 fmol/mg protein) vs. saline (B(max), 27.5 +/- 5.9 fmol/mg protein), and did not show antidepressant effect. Acute SAM and imipramine+SAM did not modify frontal cortex 5-HT(1A) receptors, and showed antidepressant effects (decrease of the immobility response of 26%, P<0.01; and 47%, P<0.001) vs. saline. All the chronic treatments showed antidepressant effects and up-regulated the hippocampus 5-HT(1A) receptors. SAM prevents the 5-HT(1A) receptor up-regulation induced by acute imipramine in the frontal cortex. This mechanism may contribute to imipramine's antidepressant effect.