Modification of the risk of post-traumatic stress disorder (PTSD) by the 5-HTTLPR polymorphisms after Lorca's earthquakes (Murcia, Spain).

Information of the modulation effect of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) on post-traumatic stress disorder (PTSD) after earthquakes is scarce and contradictory. A cross-sectional face-to-face interview survey of a representative sample of the adults was carried out after the Lorca (Spain) earthquakes (May 11, 2011). Socio-demographic variables, DSM-IV diagnostic assessment and earthquake-related stressors were obtained from the Composite International Diagnostic Interview (CIDI). The triallelic and biallelic classification of the 5-HTTLPR polymorphism were genotyped from buccal swabs. Multivariate logistic regression models were used to predict PTSD, including interaction terms to explore gene-environment (G x E) interactions. The vast majority (83%, n = 341) of the Lorca survey respondents (n = 412, 71% response rate) were genotyped. Both classifications of the 5-HTTLPR genotype were in Hardy-Weinberg equilibrium. Prior lifetime PTSD was the only variable that remained a significant predictor after adjustments. There were no significant main effects of earthquake related stressors or 5-HTTLPR. However, G x E interactions of 5-HTTLPR with high emotional impact and prior lifetime anxiety disorders were statistically significant. These results provide new evidence of the modulation effect of the 5-HTTLPR polymorphisms on PTSD risk. This information might characterize people at higher risk of developing PTSD after an earthquake exposure.

A Boron Dipyrromethene (BODIPY)-Based Cu(II) -Bipyridine Complex for Highly Selective NO Detection.

A BODIPY-containing Cu(II) -bipyridine complex for the simple selective fluorogenic detection of NO in air and in live cells is reported. The detection mechanism is based on NO-promoted Cu(II) to Cu(I) reduction, followed by demetallation of the complex, which results in the clearly enhanced emission of the boron dipyrromethene (BODIPY) unit.

Valor de la ecografía transvaginal en pacientes con metrorragia de origen endometrial / Value of transvaginal ultrasonography in patients with metrorrhagia of endometrial origin

Objetivos: Determinar los hallazgos ecográficos en pacientes con metrorragia y establecer la correlación anatomopatológica en los casos de patología endometrial. Material y métodos: Se revisaron retrospectivamente las historias clínicas y los hallazgos de imagen de las 88 pacientes que acudieron a nuestro hospital por metrorragia en paciente no gestante entre el 1 de septiembre de 2002 y el 31 de agosto de 2003. Se realizó ecografía transvaginal a todas las pacientes. En 39 casos se practicó histeroscopia diagnóstica, con toma de biopsia en 37, y en dos casos no se pudo acceder a la cavidad endometrial. Resultados: El diagnóstico ecográfico más frecuente fue el de ecografía normal (32%), y el hallazgo patológico más frecuente los miomas (27,2%). En un 38,6% de las pacientes se identificó patología endometrial. Por histeroscopia existió correlación anatomopatológica con la ecografía en todos los casos de pólipos endometriales. En los carcinomas el diagnóstico de malignidad se confirmó en un 89% con un solo falso positivo. Conclusiones: En nuestro estudio la causa más frecuente de metrorragia fue la hemorragia disfuncional con ecografía normal. El hallazgo patológico más frecuente fueron los miomas

Objectives: To determine ultrasonographic findings in patients with metrorrhagia and to establish anatomopathological correlation in cases of endometrial condition. Material and methods: The clinical records and image findings of 88 patients who came to our hospital due to metrorrhagia in non-pregnant patients between September 1, 2002 and August 31, 2003 were retrospectively reviewed. Transvaginal ultrasonography was done in all the patients. Diagnostic hysteroscopy was done in 39 cases with biopsy in 37, not being possible to reach the endometrial cavity in 2 cases. Results: The most frequent ultrasonographic diagnosis was normal findings (32%) and myoma was the most frequent pathological finding (27.2%). Endometrial pathology was identified in 38.6% of the patients. There was anatomopathological correlation by hysteroscopy with ultrasonography in all the cases of endometrial polyps. The diagnosis of malignancy in the carcinomas was verified in 89% with only one false positive. Conclusions: In our study, the most frequent cause of metrorrhagia was dysfunctional bleeding with normal ultrasonography. The most frequent pathological finding was myoma

A new pyrazolo pyrimidine derivative inhibitor of cyclooxygenase-2 with anti-angiogenic activity.

In a previous study, we reported a new pyrazolo pyrimidine derivative, N(4)-benzyl-N(6),N(6)-dimethyl-1-1(tert-butyl)-1H-pyrazolo[3,4-d]pyrimidine-6,4-diamine (DPP), which inhibited potently cyclooxygenase-2 activity in intact cell assays with minor activity against cyclooxygenase-1 (IC(50)=0.9 nM for cyclooxygenase-2 versus IC(50)=59.6 nM for cyclooxygenase-1). In the present work, this behaviour was confirmed in vivo by using the 24-h zymosan-injected mouse air pouch model (ID(50)=1.36 nM/pouch for prostaglandin E(2) level). We also studied the possible beneficial effect of DPP in the angiogenesis-dependent murine air pouch granuloma and rat paw carrageenan-induced hyperalgesia models. DPP exerted analgesic and anti-angiogenic (52% reduction in angiogenesis at 10 mg/kg, i.p.) effects that may be associated with inhibition of cyclooxygenase-2 activity.

A novel indazolo-triazolo-benzotriazepine exerts anti-inflammatory effects by inhibition of cyclooxygenase-2 activity and nitric oxide synthase-2 expression.

We have studied the anti-inflammatory activity of (6-(p-bromophenyl)amino-7-(p-chlorophenyl)indazolo[2',3':1,5]-1,2,4-triazolo[4,3-a]-1,3,5-benzotriazepine (ITB), prepared by solid-phase synthesis. This novel compound reduced the production of nitrite and PGE(2) in RAW 264.7 macrophages stimulated with lipopolysaccharide in a concentration-dependent manner. The first effect was dependent on inhibition of nitric oxide synthase-2 (NOS-2) protein expression although ITB did not modify nuclear factor-kappa B (NF-kappa B)-DNA binding. In addition, this compound inhibited cyclooxygenase-2 (COX-2) activity, which was also observed in aspirin-treated human monocytes. The anti-inflammatory effects of ITB were demonstrated in the carrageenan-induced mouse paw oedema, where this compound inhibited swelling and PGE(2) levels in inflamed paws but not in stomachs, in contrast to the dual COX-1/COX-2 inhibitor indomethacin. Inhibition of COX-2 activity and NOS-2 protein expression was confirmed in vivo using the zymosan-injected mouse air pouch model. These results suggest that synthesis of fused indazolo bis(guanidines) is a useful approach in the search for new anti-inflammatory agents.

Cacospongionolide B suppresses the expression of inflammatory enzymes and tumour necrosis factor-alpha by inhibiting nuclear factor-kappa B activation.

1. The marine product cacospongionolide B, a sesterterpene isolated from the Mediterranean sponge Fasciospongia cavernosa, is an inhibitor of secretory phospholipase A(2) with anti-inflammatory properties. In this work, we have studied the mechanism of action of this compound in the inflammatory response induced by zymosan in primary cells and in the mouse air pouch. 2. In mouse peritoneal macrophages, cacospongionolide B was able to downregulate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), resulting in decreased production of NO and prostaglandin E(2) (PGE(2)). This compound also reduced tumour necrosis factor-alpha (TNF-alpha) mRNA expression and TNF-alpha levels. 3. Cacospongionolide B inhibited nuclear factor-kappaB (NF-kappaB)-DNA binding activity and the nuclear translocation of this transcription factor. 4. Treatment of cells with cacospongionolide B impaired NF-kappaB inhibitory protein (IkappaB-alpha) phosphorylation and enhanced IkappaB-alpha expression. 5. Inhibition of iNOS, COX-2 and inflammatory mediators was confirmed in the mouse air pouch. 6. These results show that cacospongionolide B is able to control NO, PGE(2) and TNF-alpha production in vitro and in vivo, effects likely dependent on NF-kappaB inhibition.

A new ditriazine inhibitor of NF-kappaB modulates chronic inflammation and angiogenesis.

We have previously shown that a ditriazine derivative 4,10-dichloropyrido[5,6:4,5]thieno[3,2- d':3,2- d]-1, 2, 3-ditriazine (DTD) modulates acute inflammation in murine models by inhibition of leukocyte functions and expression of inducible enzymes including nitric oxide synthase and cyclooxygenase-2 (COX-2). In the present work, we have demonstrated the anti-inflammatory effect of DTD after oral administration in the rat adjuvant-induced arthritis, by reduction of interleukin-1beta and tumour necrosis factor-alpha levels and COX-2 expression in the inflamed tissues. These mediators were also significantly decreased by DTD treatment in the angiogenesis-dependent murine air pouch granuloma model, where this agent exerted anti-inflammatory and antiangiogenic effects. In vitro experiments indicated that DTD is an inhibitor of the nuclear factor-kappaB (NF-kappaB) pathway of cellular activation in macrophages, in parallel with the regulation of cytokine release. Our results suggest that the anti-inflammatory and antiangiogenic properties of DTD can be related to the inhibition of cytokine and PGE(2) production by interfering with NF-kappaB activation. This compound thus offers a therapeutic potential for the treatment of chronic inflammatory diseases with an angiogenic component, such as rheumatoid arthritis.

A pyrroloquinazoline derivative with anti-inflammatory and analgesic activity by dual inhibition of cyclo-oxygenase-2 and 5-lipoxygenase.

In a previous study, we reported a new pyrroloquinazoline derivative, 3-(4'-acetoxy-3',5'-dimethoxy)benzylidene-1,2-dihydropyrrolo[2,1-b]quinazoline-9-one (PQ), which inhibited human purified 5-lipoxygenase activity and prostaglandin E2 release in lipopolysaccharide-stimulated RAW 264.7 cells. In the present work, we show that PQ inhibits cyclo-oxygenase-2 activity in intact cell assays (human monocytes) and purified enzyme preparations (ovine isoenzymes) without affecting cyclo-oxygenase-1 activity. This behaviour was confirmed in vivo by using the zymosan-injected mouse air pouch model, where PQ caused a marked reduction in cell migration and leukotriene B4 levels at 4 h, as well as inhibition of prostaglandin E2 levels without affecting cyclo-oxygenase-2 expression at 24 h after zymosan stimulation. In addition, oral administration of this compound significantly reduced carrageenan-induced mouse paw oedema and phenyl-p-benzoquinone-induced writhings in mice. These results indicate that oral PQ exerts analgesic and anti-inflammatory effects, which are related to dual inhibition of cyclo-oxygenase-2 and 5-lipoxygenase activities.