Multiphoton Ionization of Uracil at 355 nm

We present the experimental results from ionization and dissociation by multiphoton absorption (MPI) of uracil and a mixture of uracil with Ar using a Reflectron time of flight spectrometer along with radiation from 355 nm at pulsed Nd:YAG laser . We focus on the light ions production. The MPI mass spectra show that the presence and intensity of the resulting ions depend on the density power of the laser. The resulting ions in the mass spectra are identified and found similar behavior in the case of H+ and C+ as when multiple charged ions are used. Different results were found in contrast with those, recently reported, when electrons or photons of other wavelength were used. The number of 355nm absorbed photons was calculated accordingly to Keldysh theory and similar results were fond using pure uracil or uracil-Ar mixture. Our results are compared with those obtained in other laboratories under different experimental conditions, some of them show only partial agreement and differences are discussed

Estudio de la frecuencia, distribución y rendimiento diagnóstico en las lesiones neoplásicas sincrónicas del carcinoma colo-rectal

ABSTRACT To analyse the frequency, characteristics and diagnosis of synchronic neoplastic lesions in colorectal cancer. A review was carried out of 384 colorectal cancers, diagnosed through complete colonoscopy and resected. The synchronic cancers and the characteristics of the adenomas were determined: number, size, histological type, dysplasia, as well as their localisation in the colon and with respect to the carcinoma. Twenty-eight synchronic cancers were found (7.3% of the total); 8 developed tumours and 20 malignant polyps. In 54.4% of the cases there was a synchronic adenoma. In patients with synchronic lesions, 43% showed an advanced adenoma. Twenty percent of the synchronic polyps found were proximal to the splenic flexure; 41% were distal and 38% had both localisations. Fifty-nine point one percent of the patients had some adenoma proximal to the cancer, with criteria of advanced adenoma in 13.9%. The distribution of the adenomas was more uniformly spread in the cancers with a proximal localisation (p = 0.038). Seventeen percent of the distal cancers presented synchronic lesions with a proximal colon localisation exclusively. Partial endoscopies would diagnose the distal cancers, but would omit a synchronic adenoma in 42.3% of the sigmoidoscopies and 40% of the short colonoscopies. High rates of carcinoma and synchronic adenomas were registered. We underline the high index of advanced adenomas and the frequency of synchronic lesions proximal to the cancer, which is why incomplete colonoscopies, although allowing the diagnosis of the distal cancer, omit a high percentage of synchronic adenomas, including advanced lesions. All of this confirms the need to perform a complete pre- , intra- and post operational colonoscopy in resectable colorectal cancer

Synchronous neoplastic lesions in colorectal cancer. An analysis of possible risk factors favouring presentation

Aim: few data have been published regarding the causes of synchronous lesions in patients with colorectal cancer. The aim of our study was to identify potential factors that might be implicated in the development of multicentric lesions, since this knowledge could be useful for tailored follow-up once initial synchronous lesions have been removed. Methods: we retrospectively reviewed 382 colorectal cancer cases diagnosed by total colonoscopy and histological study of surgical specimens. We divided our population into 2 groups, based on whether they had synchronous lesions or otherwise. Several data related to personal and family history, habits, symptoms, and tumor characteristics were assessed. Univariate and multivariate statistical analyses were performed. Results: 208 (54.5%) patients had synchronous adenomas and 28 (7.3%) had synchronous cancer. A multivariate analysis showed that the following parameters were consistently related to the presence of multicentric lesions –male gender: OR = 1.97; CI = 1.13-3.45; p = 0.017; age ≥ 59 years: OR = 2.57; CI = 1.54-4.29; p < 0.001; personal history of colonic adenomas: OR = 3.04; CI = 1.04-8.85; p = 0.042; and obstructive tumors: OR = 0.48; CI = 0.27-0.85; p = 0.012. Conclusion: our results show that several parameters that are easy to measure could be considered risk factors for the development of multicentric lesions. These factors need to be confirmed with follow-up studies analyzing their role in patients with and without metachronic lesions once all synchronous lesions have been removed

Análisis de la posible influencia de las lesiones sincrónicas en el pronóstico del cáncer colorrectal resecado

Aim: To analyze the relationship between synchronous lesions in patients with colorectal cancer and their prognostic value. Patients and methods: We have retrospectively reviewed 369 patients with resected colorectal cancer. We compared the rate of apparently curative surgery, progression and tumoral relapse, development of extracolonic cancer and mortality between patients with and without synchronous cancer. Afterwards, we analyzed the same parameters in colorectal cancer with and without synchronous adenomas. Finally, we repeated the analysis after stratification of cancers in 2 groups according to pTNM staging: 0-I-II stage vs III-IV. Results: We found synchronous adenomas in 54.7% of our patients and synchronous cancers in 7.6%. Follow-up period of groups with and without synchronous lesions were: 70.8 ± 22.9 and 67.2 ± 24.5 months (p = 0.55) respectivelly. Synchronous cancers showed higher mortality: 35.7 vs. 14.4%: p = 0.006; OR = 3.31 (1.33-8.13), higher tumoral progression : 39.3 vs. 19.1%: p = 0.011; OR = 2.75 (1.14-6.56) and higher relapse rate: 10.7 vs. 3.5%: p = 0.096. Stratifying according to stage, patients with stage 0-I-II and synchronous cancer showed worse prognosis: mortality = 27.7 vs. 8.1%, p = 0.019; OR = 4.45 (1.2-15.1), tumoral progression = 27.8 vs. 8.5%, p = 0.02; OR = 4.12 (1.14-14.19), and extracolonic cancer = 16.7 vs. 6.4% p = 0.095. There were no statistical differences between cases with and without synchronous adenomas. Conclusions: Synchronous cancers showed worse prognosis after resection, with higher rate of tumoral progression and mortality. This difference is focused on the cases diagnosed in stage 0-I-II, not being found in III-IV. The presence of synchronous adenomas doesn’t influence prognosis

Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model.

Recent findings suggest that part of the anti-tumor effects of several chemotherapeutic agents require an intact immune system. This is in part due to the induction of immunogenic cell death. We have identified a gallotannin-rich fraction, obtained from Caesalpinia spinosa (P2Et) as an anti-tumor agent in both breast carcinoma and melanoma. Here, we report that P2Et treatment results in activation of caspase 3 and 9, mobilization of cytochrome c and externalization of annexin V in tumor cells, thus suggesting the induction of apoptosis. This was preceded by the onset of autophagy and the expression of immunogenic cell death markers. We further demonstrate that P2Et-treated tumor cells are highly immunogenic in vaccinated mice and induce immune system activation, clearly shown by the generation of interferon gamma (IFN-γ) producing tyrosine-related protein 2 antigen-specific CD8+ T cells. Moreover, the tumor protective effects of P2Et treatment were abolished in immunodeficient mice, and partially lost after CD4 and CD8 depletion, indicating that P2Et's anti-tumor activity is highly dependent on immune system and at least in part of T cells. Altogether, these results support the hypothesis that the gallotannin-rich fraction P2Et's anti-tumor effects are mediated to a great extent by the endogenous immune response following to the exposure to immunogenic dying tumor cells

Circulating microparticles from patients with obstructive sleep apnea enhance vascular contraction: mandatory role of the endothelium

Obstructive sleep apnea (OSA) is characterized by repetitive apnea-hypopnea cycles during sleep associated with oxygen desaturation and sleep disruption. We evaluated the role of circulating microparticles (MPs) from patients with OSA in the regulation of vascular function. MPs from whole blood from patients with OSA or control subjects were injected i.v. into mice. Injection of MPs from patients with OSA induced ex vivo vascular hyperreactivity in aortas with functional endothelium but, in contrast, hyporeactivity in vessels without functional endothelium. Vascular hyperreactivity was blunted in the presence of a nitric oxide synthase inhibitor alone or combined with the cyclooxygenase inhibitor indomethacin. MPs from patients with OSA reduced endothelial nitric oxide synthase activity and nitric oxide production, increased aortic cyclooxygenase-1 and cyclooxygenase-2 expression, and increased thromboxane A(2) and prostacyclin production. Blockade of thromboxane A(2) receptor did not affect the serotonin response in arteries from OSA MP-treated mice. A superoxide dismutase mimetic reduced the vascular hyperreactivity induced by MPs from patients with OSA but had no effect on contraction in vessels from control and non-OSA MP-treated mice. These data provide evidence that circulating MPs from patients with OSA induce ex vivo vascular hyperreactivity with the obligatory role of the endothelium and subtle interactions between the nitric oxide and cyclooxygenase pathways and metabolites. These results highlight the participation of MPs in vascular dysfunction associated with OSA

Preserved insulin vasorelaxation and up-regulation of the Akt/eNOS pathway in coronary arteries from insulin resistant obese Zucker rats

Obesity is associated with insulin resistance in the peripheral vasculature and is an important risk factor for coronary artery disease. The current study assessed whether the vascular effects and the signaling pathways of insulin are impaired in coronary arteries from a rat model of genetic obesity. Intramyocardial arteries from obese Zucker rats (OZR) and lean Zucker rats (LZR) were mounted in microvascular myographs to assess insulin vasoactive effects and the proteins of the insulin pathway were determined by Western blotting. The endothelium-dependent and nitric oxide (NO)-mediated vasorelaxant effect of insulin was similar in arteries from LZR and OZR and blunted by inhibition of phosphatidylinositol 3-kinase (PI3K) and endothelial NO synthase (eNOS), but unaltered by either mitogen activated protein kinase (MAPK) or endothelin (ET) receptor blockade. Basal levels of phospho-eNOS Ser1177 and phospho-Akt Ser473 were up-regulated in OZR, and insulin increased phosphorylation of eNOS and Akt in both LZR and OZR. Moreover, insulin enhanced Akt expression in LZR. Basal and insulin-stimulated levels of phospho-MAPK p42/p44 were lower in OZR and palmitic acid reduced these levels in LZR. Coronary arteries are protected from vascular IR. The results underscore the fact that preservation of insulin-mediated vasorelaxation along with an up-regulation of the Akt/eNOS pathway and an impairment of the MAPK cascade account for this protection

Cardiotrophin-1 defends the liver against ischemia-reperfusion injury and mediates the protective effect of ischemic preconditioning

Ischemia-reperfusion (I/R) liver injury occurs when blood flow is restored after prolonged ischemia. A short interruption of blood flow (ischemic preconditioning [IP]) induces tolerance to subsequent prolonged ischemia through ill-defined mechanisms. Cardiotrophin (CT)-1, a cytokine of the interleukin-6 family, exerts hepatoprotective effects and activates key survival pathways like JAK/STAT3. Here we show that administration of CT-1 to rats or mice protects against I/R liver injury and that CT-1-deficient mice are exceedingly sensitive to this type of damage. IP markedly reduced transaminase levels and abrogated caspase-3 and c-Jun-NH2-terminal kinase activation after I/R in normal mice but not in CT-1-null mice. Moreover, the protective effect afforded by IP was reduced by previous administration of neutralizing anti-CT-1 antibody. Prominent STAT3 phosphorylation in liver tissue was observed after IP plus I/R in normal mice but not in CT-1-null mice. Oxidative stress, a process involved in IP-induced hepatoprotection, was found to stimulate CT-1 release from isolated hepatocytes. Interestingly, brief ischemia followed by short reperfusion caused mild serum transaminase elevation and strong STAT3 activation in normal and IL-6-deficient mice, but failed to activate STAT3 and provoked marked hypertransaminasemia in CT-1-null animals. In conclusion, CT-1 is an essential endogenous defense of the liver against I/R and is a key mediator of the protective effect induced by IP

Ferromagnetic/superconducting proximity effect in La0.7Ca0.3MnO3 / YBa2Cu3O7 superlattices

We study the interplay between magnetism and superconductivity in high quality YBa2Cu3O7 (YBCO) / La0.7Ca0.3MnO3(LCMO)superlattices. We find evidence for the YBCO superconductivity depression in presence of the LCMO layers. We show that due to its short coherence length superconductivity survives in the YBCO down to much smaller thickness in presence of the magnetic layer than in low Tc superconductors. We also find that for a fixed thickness of the superconducting layer, superconductivity is depressed over a thickness interval of the magnetic layer in the 100 nm range. This is a much longer length scale than that predicted by the theory of ferromagnetic/superconducting proximity effect.Comment: 10 pages + 5 figures, submitted to Phys. Rev.