Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated. METHODS: FXR and TGR5 expression was determined in human CCA tissues and cell lines. An orthotopic model of CCA was established in immunodeficient mice and tumor volume was monitored by magnetic resonance imaging under chronic administration of the specific FXR or TGR5 agonists, obeticholic acid (OCA) or INT-777 (0,03% in chow; Intercept Pharmaceuticals), respectively. Functional effects of FXR or TGR5 activation were evaluated on CCA cells in vitro. RESULTS: FXR was downregulated whereas TGR5 was upregulated in human CCA tissues compared to surrounding normal liver tissue. FXR expression correlated with tumor differentiation and TGR5 correlated with perineural invasion. TGR5 expression was higher in perihilar than in intrahepatic CCAs. In vitro, FXR was downregulated and TGR5 was upregulated in human CCA cells compared to normal human cholangiocytes. OCA halted CCA growth in vivo, whereas INT-777 showed no effect. In vitro, OCA inhibited CCA cell proliferation and migration which was associated with decreased mitochondrial energy metabolism. INT-777, by contrast, stimulated CCA cell proliferation and migration, linked to increased mitochondrial energy metabolism. CONCLUSION: Activation of FXR inhibits, whereas TGR5 activation may promote, CCA progression by regulating proliferation, migration and mitochondrial energy metabolism. Modulation of FXR or TGR5 activities may represent potential therapeutic strategies for CCA.

Orígenes de la psicoterapia / Origins of psycotherapy

Partiendo del chamán como iniciador de las prácticas que hoy conocemos como psicoterapia, el autor analiza la figura de éste, como sabio poeta y vidente en el contexto de la Grecia clásica de la antigüedad, época donde las concepciones míticas inician su viraje al mundo del logos, base de nuestra cultura occidental, y cuna del logos, como terapia. En dicha transición, el conjuro (epode) propio de las prácticas chamánicas desembocara, por un lado, en el logos filosófico y por ende en la palabra curativa, y por el otro, en la medicina. Dicha escisión, presenta un claro paralelismo con la dicotomía actual entre la physis, y el logos inmerso en las técnicas psicoterapéuticas de hoy en día. Se propone como nuevo paradigma, la Nueva Hermenéutica, que integra la physis y la palabra a su unidad de origen. (AU)

Determination of titanium NMR parameters of ATiO3 compounds: correlations with structural distortion.

Solid state 47,49Ti NMR spectra have been obtained for a number of perovskite and ilmenite ATiO3 compounds. The 49Ti quadrupole coupling constant varies from 2.75 MHz (CaTiO3) to 15.5 MHz (MgTiO3) and the electric field gradient at the titanium site was found to correlate well with the shear strain, independent of structure. The chemical shift in the perovskite structures varies by approximately 160 ppm and correlates well with the mean Ti-O distance. The 25Mg and 113Cd NMR parameters are also reported for the relevant compounds.

Depression in three populations in the Basque country--a comparison with Britain.

A psychiatric survey in three regions of the Basque Autonomous Community aimed to replicate two British surveys, in London and a rural area of Scotland, investigating both prevalence of psychiatric disorder and its relationship with certain key psychosocial factors. The Spanish rural-urban differences in rates of depression and anxiety closely paralleled the earlier British results. As in Britain, Spanish rural rates of depression were lower among those most integrated into the traditional family ways of life, but in contrast to Britain the urban rates did not vary with social class or the presence of children at home. As in Britain, severe life event and major difficulties were associated with onset of depression, and varied in prevalence and type with degree of integration with the traditional lifestyle. The protective role of intimate confiding with a partner against depressive onset was confirmed among non-churchgoers in Bilbao, but not among churchgoers, while in the rural samples there was only a nonsignificant trend.

Alpha 2-adrenoceptor-mediated inhibition of platelet adenylate cyclase and induction of aggregation in major depression. Effect of long-term cyclic antidepressant drug treatment.

The functional status of platelet alpha 2-adrenoceptors in patients with major depression has been assessed by simultaneously measuring both a biochemical mechanism of transduction of receptor activation (inhibition of adenylate cyclase activity) and a physiologic response of the receptor (induction of aggregation). The inhibitory effects induced by epinephrine and UK 14304 on adenylate cyclase activity were unchanged, while the aggregation responses induced by the same alpha 2-adrenoceptor agonists were potentiated, which indicated receptor supersensitivity. In depressed (n = 30) and euthymic (n = 11) patients as well as in control subjects (n = 66), there was a clear dissociation between inhibition of adenylate cyclase activity and induction of aggregation, indicating that the two responses represent different phenomena of alpha 2-adrenoceptor activation. alpha 2-Adrenoceptor-mediated platelet aggregation could represent a better marker than inhibition of adenylate cyclase to assess functional changes of the receptor in depression. Both of these functional responses are desensitized after long-term antidepressant treatment.

[Solitary extramedullary plasmocytoma of the small intestine]. / Plasmocitoma extramedular solitario del intestino delgado.

A case is presented of PES of the small intestine debuting with subocclusive crises. After the preoperative study the patient was diagnosed as probable neoplasm of the small intestine. In the operation was confirmed an annular stenosing ileal tumor that respected the serosa. Ample intestinal resection was practiced with a normal postoperative recovery. The pathology report indicated plasmocytoma, the immunoperoxidase technique being negative. The existence of multiple myeloma and other lesions at a distance was excluded. Almost a year after the operation the patient remains asymptomatic and free of recurrence. A review of the literature is offered.