Angiotensin II type 1 receptor blockade partially attenuates hypoxia-induced pulmonary hypertension in newborn piglets: relationship with the nitrergic system

The objective of this study was to observe possible interactions between the renin-angiotensin and nitrergic systems in chronic hypoxia-induced pulmonary hypertension in newborn piglets. Thirteen chronically instrumented newborn piglets (6.3 +/- 0.9 days; 2369 +/- 491 g) were randomly assigned to receive saline (placebo, P) or the AT(1) receptor (AT(1)-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO(2) = 0.12). During hypoxia, pulmonary arterial pressure (Ppa; P < 0.0001), pulmonary vascular resistance (PVR; P < 0.02) and the pulmonary to systemic vascular resistance ratio (PVR/SVR; P < 0.05) were significantly attenuated in the L (N = 7) group compared to the P group (N = 6). Western blot analysis of lung proteins showed a significant decrease of endothelial NOS (eNOS) in both P and L animals, and of AT(1)-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT(1)-R tended to decrease in L animals. Inducible NOS (iNOS) did not differ among P, L, and C animals and iNOS immunohistochemical staining in macrophages was significantly more intense in L than in P animals (P < 0.01). The vascular endothelium showed moderate or strong eNOS and AT(1)-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT(1)-R staining, but C animals showed weak iNOS and AT(1)-R staining. Macrophages of L and P animals showed moderate and weak AT(2)-R staining, respectively, but the endothelium of all groups only showed weak staining. In conclusion, pulmonary hypertension induced by chronic hypoxia in newborn piglets is partially attenuated by AT(1)-R blockade. We suggest that AT(1)-R blockade might act through AT(2)-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets.

Partially Observed Markov Random Fields Are Variable Neighborhood Random Fields

The present paper has two goals. First to present a natural example of a new class of random fields which are the variable neighborhood random fields. The example we consider is a partially observed nearest neighbor binary Markov random field. The second goal is to establish sufficient conditions ensuring that the variable neighborhoods are almost surely finite. We discuss the relationship between the almost sure finiteness of the interaction neighborhoods and the presence/absence of phase transition of the underlying Markov random field. In the case where the underlying random field has no phase transition we show that the finiteness of neighborhoods depends on a specific relation between the noise level and the minimum values of the one-point specification of the Markov random field. The case in which there is phase transition is addressed in the frame of the ferromagnetic Ising model. We prove that the existence of infinite interaction neighborhoods depends on the phase.

Characterization of a Novel Oral Glucocorticoid System and Its Possible Role in Disease

Synthetic corticosteroids are used widely for the treatment of a variety of diseases of the mouth. However, little is known as to whether the oral mucosa is able to modulate the local concentration of active corticosteroids or to produce steroids de novo. This has important clinical implications, because tissue-specific regulation of glucocorticoids is a key determinant of the clinical efficacy of these drugs. In the present study, we show that oral fibroblasts and keratinocytes expressed ACTH receptor (MC2R), glucocorticoid receptor (GR), and 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs). Unlike keratinocytes, fibroblasts lacked 11 beta-HSD2 and could not effectively deactivate exogenously administered cortisol. However, both cell types were able not only to activate cortisone into the active form cortisol, but also to synthesize cortisol de novo following stimulation with ACTH. 11 beta-HSD2, the enzyme controlling cortisol deactivation, exhibited different patterns of expression in normal (squamous epithelium and salivary glands) and diseased oral mucosa (squamous cell carcinoma and mucoepidermoid carcinoma). Blocking of endogenous cortisol catabolism in keratinocytes with the 11 beta-HSD2 inhibitor 18 beta-glycyrrhetinic acid mimicked the effect of exogenous administration of hydrocortisone and partially prevented the detrimental effects induced by pemphigus vulgaris sera. Analysis of the data demonstrates that a novel, non-adrenal glucocorticoid system is present in the oral mucosa that may play an important role in disease.

Evaluation of the micro-hardness and fracture toughness of amorphous and partially crystallized 3CaO center dot P2O5-SiO2-MgO bioglasses

In this work, the effect of the indentation load on the results of hardness and fracture toughness, determined by Vickers micro-hardness measurements, of some glasses and glass-ceramics has been investigated. Furthermore, in order to verify the effect of crystallinity on the results, glasses of composition 52.75 wt.% 3CaO center dot P2O5, 30 wt.% SiO2 and 17.25 wt.% MgO were fused at 1600 degrees C for 4 h and annealed at 700 degrees C for 2h, and further heat-treated at 700, 775, 800 and 900 degrees C for 4h. The obtained materials were analyzed by high resolution X-ray diffraction, HRXRD, to determine the crystallization degree in function of the heat-treatment temperature. The hardness of the different specimens was determined by Vickers' micro-hardness measurements under various loads. It has been observed that with increasing crystallization of the materials their hardness increased. Furthermore, it has been possible to verify the so-called indentation size effect (ISE), i.e. hardness decreases as the indentation depth, under higher loads, increases. This effect has been more pronounced in the glass-ceramic samples. Fracture toughness has been determined by the crack length induced by the Vickers indentations and relating them to the applied loads. Glass materials presented a fracture pattern with characteristics of cleavage, forming cracks of the half-penny shaped type, while the glass-ceramic materials exhibited crack bridging effects and Palmqvist type cracks. (C) 2011 Elsevier B.V. All rights reserved.

Apoptotic Cells Contribute to Melanoma Progression and This Effect is Partially Mediated by the Platelet-Activating Factor Receptor

There is evidence that the platelet-activating factor receptor (PAFR) is involved in the clearance of apoptotic cells by macrophages, and that this is associated with anti-inflammatory phenotype. Our group has previously shown that coinjection of a large number of apoptotic cells can promote tumor growth from a subtumorigenic dose of melanoma cells. Here, we studied the involvement of the PAFR in the tumor growth promoting effect of apoptotic cells. A sub-tumorigenic dose of melanoma cells (Tm1) was coinjected with apoptotic Tm1 cells, subcutaneously in the flank of C57Bl/6 mice, and the volume was monitored for 30 days. Animals received the PAFR antagonists, WEB2170 or PCA4248 (5 mg/kg body weight) or vehicle, by peritumoral daily injection for 5 days. Results showed that PAFR antagonists significantly inhibited the tumor growth induced by the coinjection of a subtumorigenic dose of melanoma cells together with apoptotic cells. This was accompanied by inhibition of early neutrophil and macrophage infiltration. Addition of (platelet-activating factor) to this system has no significant effect. PAFR antagonists did not affect the promoting effect of carrageenan. We suggest that the recognition of apoptotic cells by phagocytes leads to activation of PAFR pathways, resulting in a microenvironment response favorable to melanoma growth.

Composite connections in slim-floor system: An experimental study

This paper reports the results of full-scale tests in beam-to-column connections for composite slim floor systems, including tests on Bare Steel connection and composite connection. The tested system consists of a concrete-filled composite column and a composite floor where an asymmetric steel beam is connected to a composite column by shear steel plates. Tests results previously obtained on partially encased composite beams were used to define the position of the headed studs in the slim floor system. Based on the obtained results of connections, the composite and Bare Steel connection behaved as semi-rigid and nominally pinned respectively. The tests results also indicated a significant contribution of the slim floor to the moment capacity of the connection. (C) 2011 Elsevier Ltd. All rights reserved.

Spontaneous combined rupture of a pelvicalyceal cyst into the collector system and retroperitoneal space during the acquisition of computed tomography scan images: a case report

Abstract Introduction Pelvicalyceal cysts are common findings in autopsies and can manifest with a variety of patterns. These cystic lesions are usually a benign entity with no clinical significance unless they enlarge enough to cause compression of the adjacent collecting system and consequently obstructive uropathy. Few cases of the spontaneous rupture of pelvicalyceal renal cysts have been published and to the best of our knowledge there is no report of a combined rupture to collector system and retroperitoneal space documented during a multiphase computed tomography. Case presentation We report a case of a ‘real-time’ spontaneous rupture of a pelvicalyceal cyst into the collecting system with fistulization into the retroperitoneum. The patient was a 78-year-old Caucasian man with a previous history of renal stones and a large pelvicalyceal renal cyst who was admitted to our Emergency department with acute right flank pain. A multiphase computed tomography was performed and the pre-contrast images demonstrated a right pelvicalyceal renal cyst measuring 12.0 × 6.1cm in the lower pole causing moderate dilation of the upper right renal collection system. In addition, a partially obstructive stone on the left distal ureter with mild left hydronephrosis was noted. The nephrographic phase did not add any new information. The excretory phase (10-minute delay) demonstrated a spontaneous rupture of the cyst into the pelvicalyceal system with posterior fistulization into the retroperitoneal space. Conclusion In this case study we present time-related changes of a rare pelvicalyceal cyst complication, which to the best of our knowledge has fortunately not been previously documented. Analysis of the sequential images and comparison with an earlier scan allowed us to better understand the physiopathological process of the rupture, the clinical presentation and to elaborate hypotheses for its etiopathogenesis.

Influence of the dopaminergic system, CREB, and transcription factor-κB on cocaine neurotoxicity

Cocaine is a widely used drug and its abuse is associated with physical, psychiatric and social problems. Abnormalities in newborns have been demonstrated to be due to the toxic effects of cocaine during fetal development. The mechanism by which cocaine causes neurological damage is complex and involves interactions of the drug with several neurotransmitter systems, such as the increase of extracellular levels of dopamine and free radicals, and modulation of transcription factors. The aim of this review was to evaluate the importance of the dopaminergic system and the participation of inflammatory signaling in cocaine neurotoxicity. Our study showed that cocaine activates the transcription factors NF-κB and CREB, which regulate genes involved in cellular death. GBR 12909 (an inhibitor of dopamine reuptake), lidocaine (a local anesthetic), and dopamine did not activate NF-κB in the same way as cocaine. However, the attenuation of NF-κB activity after the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, suggests that the activation of NF-κB by cocaine is, at least partially, due to activation of D1 receptors. NF-κB seems to have a protective role in these cells because its inhibition increased cellular death caused by cocaine. The increase in BDNF (brain-derived neurotrophic factor) mRNA can also be related to the protective role of both CREB and NF-κB transcription factors. An understanding of the mechanisms by which cocaine induces cell death in the brain will contribute to the development of new therapies for drug abusers, which can help to slow down the progress of degenerative processes.