Angiotensin II induces soluble fms-Like tyrosine kinase-1 release via calcineurin signaling pathway in pregnancy

Maternal endothelial dysfunction in preeclampsia is associated with increased soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating antagonist of vascular endothelial growth factor and placental growth factor. Angiotensin II (Ang II) is a potent vasoconstrictor that increases concomitant with sFlt-1 during pregnancy. Therefore, we speculated that Ang II may promote the expression of sFlt-1 in pregnancy. Here we report that infusion of Ang II significantly increases circulating levels of sFlt-1 in pregnant mice, thereby demonstrating that Ang II is a regulator of sFlt-1 secretion in vivo. Furthermore, Ang II stimulated sFlt-1 production in a dose- and time-dependent manner from human villous explants and cultured trophoblasts but not from endothelial cells, suggesting that trophoblasts are the primary source of sFlt-1 during pregnancy. As expected, Ang II-induced sFlt-1 secretion resulted in the inhibition of endothelial cell migration and in vitro tube formation. In vitro and in vivo studies with losartan, small interfering RNA specific for calcineurin and FK506 demonstrated that Ang II-mediated sFlt-1 release was via Ang II type 1 receptor activation and calcineurin signaling, respectively. These findings reveal a previously unrecognized regulatory role for Ang II on sFlt-1 expression in murine and human pregnancy and suggest that elevated sFlt-1 levels in preeclampsia may be caused by a dysregulation of the local renin/angiotensin system.

Reduced Plasma Angiotensin Ii Levels Are Reversed By Hydroxyurea Treatment In Mice With Sickle Cell Disease.

Sickle cell disease (SCD) pathogenesis leads to recurrent vaso-occlusive and hemolytic processes, causing numerous clinical complications including renal damage. As vasoconstrictive mechanisms may be enhanced in SCD, due to endothelial dysfunction and vasoactive protein production, we aimed to determine whether the expression of proteins of the renin-angiotensin system (RAS) may be altered in an animal model of SCD. Plasma angiotensin II (Ang II) was measured in C57BL/6 (WT) mice and mice with SCD by ELISA, while quantitative PCR was used to compare the expressions of the genes encoding the angiotensin-II-receptors 1 and 2 (AT1R and AT2R) and the angiotensin-converting enzymes (ACE1 and ACE2) in the kidneys, hearts, livers and brains of mice. The effects of hydroxyurea (HU; 50-75mg/kg/day, 4weeks) treatment on these parameters were also determined. Plasma Ang II was significantly diminished in SCD mice, compared with WT mice, in association with decreased AT1R and ACE1 expressions in SCD mice kidneys. Treatment of SCD mice with HU reduced leukocyte and platelet counts and increased plasma Ang II to levels similar to those of WT mice. HU also increased AT1R and ACE2 gene expression in the kidney and heart. Results indicate an imbalanced RAS in an SCD mouse model; HU therapy may be able to restore some RAS parameters in these mice. Further investigations regarding Ang II production and the RAS in human SCD may be warranted, as such changes may reflect or contribute to renal damage and alterations in blood pressure.

Class II Correction with the Cantilever Bite Jumper

Objective: To identify the skeletal, dentoalveolar, and soft tissue changes that occur during Class II correction with the Cantilever Bite Jumper (CBJ). Materials and Methods: This prospective cephalometric study was conducted on 26 subjects with Class II division 1 malocclusion treated with the CBJ appliance. A comparison was made with 26 untreated subjects with Class II malocclusion. Lateral head films from before and after CBJ therapy were analyzed through conventional cephalometric and Johnston analyses. Results: Class II correction was accomplished by means of 2.9 mm apical base change, 1.5 mm distal movement of the maxillary molars, and 1.1 mm mesial movement of the mandibular molars. The CBJ exhibited good control of the vertical dimension. The main side effect of the CBJ is that the vertical force vectors of the telescope act as lever arms and can produce mesial tipping of the mandibular molars. Conclusions: The Cantilever Bite Jumper corrects Class II malocclusions with similar percentages of skeletal and dentoalveolar effects. (Angle Orthod. 2009:79;)

High sucrose intake in rats is associated with increased ACE2 and angiotensin-(1-7) levels in the adipose tissue

Sucrose-fed rats, a model of metabolic syndrome, are characterized by insulin resistance, obesity, hypertension, and high plasma levels of triacylglycerols and angiotensin II (Ang II). However, whether tissue renin-angiotensin system (RAS) is altered in metabolic syndrome is unclear. To study this issue, food ad libitum and water (C) or 20% sucrose solution (SC) were given to adult male Wistar rats, for 30 days. Body weight (BW), blood pressure (BP), epididymal adipose tissue (EPI) mass, rate of in vivo fatty acid (FA) synthesis in EPI, circulating glucose, insulin, leptin, angiotensins I and II, triacylglycerols, and plasma renin (PRA) and angiotensin-converting enzyme (ACE) activities were evaluated. In kidneys and EPI, gene and protein expression of type 1 (AT(1)) and 2 (AT(2)) Ang II receptors, ACE, angiotensinogen (ACT) as well as protein expression of angiotensin-converting enzyme 2 (ACE2) were determined. In both tissues, Ang I, Ang II and Ang-(1-7) contents were also measured by HPLC. In SC rats higher BP, EPI mass, circulating triacylglycerols, insulin, leptin, PRA and, Ang II were found. In EPI, the rate of in vivo FA synthesis was associated with increased Ang-(1-7), protein expression of AT(1) and AT(2) receptors, ACE2, ACT, and gene expression of ACT although a reduction in ACE activity and in adipose Ang I and Ang II contents was observed. In kidneys, AT(1) and AT(2), ACE and ACT gene and protein expression as well as protein expression of ACE2 were unaltered while Ang II, Ang-(1-7) and ACE activity increased. These RAS component changes seem to be tissue specific and possibly are related to enhancement of FA synthesis, EPI mass and hypertension. (C) 2010 Elsevier B.V. All rights reserved.

Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling

Angiotensin (Ang) I-converting enzyme (ACE) is involved in the control of blood pressure by catalyzing the conversion of Ang I into the vasoconstrictor Ang II and degrading the vasodilator peptide bradykinin. Human ACE also functions as a signal transduction molecule, and the binding of ACE substrates or its inhibitors initiates a series of events. In this study, we examined whether Ang II could bind to ACE generating calcium signaling. Chinese hamster ovary cells transfected with an ACE expression vector reveal that Ang II is able to bind with high affinity to ACE in the absence of the Ang II type 1 and type 2 receptors and to activate intracellular signaling pathways, such as inositol 1,4,5-trisphosphate and calcium. These effects could be blocked by the ACE inhibitor, lisinopril. Calcium mobilization was specific for Ang II, because other ACE substrates or products, namely Ang 1-7, bradykinin, bradykinin 1-5, and N-acetyl-seryl-aspartyl-lysyl-proline, did not trigger this signaling pathway. Moreover, in Tm5, a mouse melanoma cell line endogenously expressing ACE but not Ang II type 1 or type 2 receptors, Ang II increased intracellular calcium and reactive oxygen species. In conclusion, we describe for the first time that Ang II can interact with ACE and evoke calcium and other signaling molecules in cells expressing only ACE. These findings uncover a new mechanism of Ang II action and have implications for the understanding of the renin-Ang system. (Hypertension. 2011;57:965-972.) . Online Data Supplement

Treatment stability in patients with Class II malocclusion treated with 2 maxillary premolar extractions or without extractions

Introduction: The purpose of this study was to compare the occlusal stability of Class II malocclusion treatment with and without extraction of 2 maxillary premolars. Methods: A sample of 59 records from patients with complete Class II malocclusion was used. This sample was divided into 2 groups with the following characteristics: group 1, comprising 29 patients treated without extractions, and group 2, comprising 30 patients treated with extraction of 2 maxillary premolars. Dental cast measurements were obtained before and after treatment and at a minimum of 2.4 years after treatment. The pretreatment, posttreatment, and postretention occlusal statuses were evaluated with the peer assesment rating index. The occlusal indexes at the postretention stage and the posttreatment changes and percentages of posttreatment changes were compared with t tests. Results: The nonextraction and the 2 maxillary premolar extraction treatment protocols of complete Class II malocclusions had no statistically significant differences in occlusal stability. Conclusions: Finishing Class II malocclusion treatment with the molars in a Class II relationship has similar occlusal stability as finishing with the molars in a Class I relationship. (Am J Orthod Dentofacial Orthop 2010;138:16-22)

Treatment of a Class II subdivision malocclusion with multiple congenitally missing teeth

This case report describes the treatment of a patient with a Class II Division 1 subdivision right malocclusion with 8 congenitally missing teeth, incompetent lips, and incisor protrusion. The treatment plan included extractions and space closure with retraction of the anterior teeth; symmetric mechanics were used in the mandibular arch and asymmetric mechanics in the maxillary arch. Because of the mechanics used, some midline deviations were expected. Knowledge of diagnosis and treatment planning of asymmetric malocclusions and dental esthetics are essential for success when correcting asymmetic problems, but, even so, small clinical compromises should be expected. (Am J Orthod Dentofacial Orthop 2009; 135: 663-70)

Influence of cephalometric characteristics on the occlusal success rate of Class II malocclusions treated with 2-and 4-premolar extraction protocols

Introduction: The objectives of this investigation were to compare the initial cephalometric characteristics of complete Class II Division 1 malocclusions treated with 2 or 4 premolar extractions and to verify their influence on the occlusal success rate of these treatment protocols. Methods: A sample of 98 records from patients with complete Class II Division 1 malocclusion was divided into 2 groups with the following characteristics: group 1 consisted of 55 patients treated with 2 maxillary first premolar extractions at an initial mean age of 13.07 years; group 2 included 43 patients treated with 4 premolar extractions, with an initial mean age of 12.92 years. Initial and final occlusal statuses were evaluated on dental casts with Grainger`s treatment priority index (TPI), and the initial cephalometric characteristics were obtained from the pretreatment cephalograms. The initial cephalometric characteristics and the initial and final occlusal statuses of the groups were compared with the t test. A multiple regression analysis was used to evaluate the influence of all variables in the final TPI. Results: The 2-premolar extraction protocol provided a statistically smaller TPI and consequently a better occlusal success rate than the 4-premolar extraction protocol. The 4-premolar extraction group had statistically smaller apical base lengths, more vertical facial growth patterns, and greater hard- and soft-tissue convexities at pretreatment than the 2-premolar extraction group. However, the multiple regression analysis showed that only the extraction protocol was significantly associated with the final occlusal status. Conclusions: The initial cephalometric characteristics of the groups did not influence the occlusal success rate of these 2 treatment protocols.

Cephalometric evaluation of Class II malocclusion treatment with cervical headgear and mandibular fixed appliances

The present study aimed to evaluate the cephalometric changes in Class II patients treated exclusively with cervical headgear (CHG) in the maxillary arch and fixed appliances in the mandibular arch as compared with a control group. The sample comprised 82 lateral cephalograms obtained pre- (T1) and post- (T2) treatment/observation of 41 subjects, divided into two groups: group 1-25 Class II division 1 patients (20 females and five males), with a mean pre-treatment age of 10.4 years, treated for a mean period of 2.5 years and group 2-16 Class II untreated subjects (12 females and four males), with a mean initial age of 9.9 years, followed for a mean period of 2.2 years. Treatment changes between the groups were compared by means of t-tests. The results showed restriction of maxillary forward displacement and also a restriction in maxillary length growth, improvement in the maxillomandibular relationship, restriction of mandibular incisor vertical development, reduction in overjet and overbite, and improvement in molar relationship. It was concluded that this treatment protocol corrected the Class II malocclusion characteristics primarily through maxillary forward growth restriction.

Apropriação de conteúdos do conhecimento explícito da língua por alunos do 2.º ano do 1.º ciclo do ensino básico

Relatório de Estágio apresentado à Escola Superior de Educação de Lisboa para obtenção de grau de mestre em Ensino do 1.º e 2.º Ciclo do Ensino Básico

Study of Helium II heat transport phenomena in superconducting rutherford type cables

This thesis is a study of how heat is transported in non-steady-state conditions from a superconducting Rutherford cable to a bath of superfluid helium (He II). The same type of superconducting cable is used in the dipole magnets of the Large Hadron Collider (LHC). The dipole magnets of the LHC are immersed in a bath of He II at 1.9 K. At this temperature helium has an extremely high thermal conductivity. During operation, heat needs to be efficiently extracted from the dipole magnets to keep their superconducting state. The thermal stability of the magnets is crucial for the operation of the LHC, therefore it is necessary to understand how heat is transported from the superconducting cables to the He II bath. In He II the heat transfer can be described by the Landau regime or by the Gorter-Mellink regime, depending on the heat flux. In this thesis both measurements and numerical simulation have been performed to study the heat transfer in the two regimes. A temperature increase of 8 2 mK of the superconducting cables was successfully measured experimentally. A new numerical model that covers the two heat transfer regimes has been developed. The numerical model has been validated by comparison with existing experimental data. A comparison is made between the measurements and the numerical results obtained with the developed model.

Angiotensin II receptor blockade prevents acute renal sodium retention induced by low levels of orthostatic stress.

BACKGROUND: Depending on its magnitude, lower body negative pressure (LBNP) has been shown to induce a progressive activation of neurohormonal, renal tubular, and renal hemodynamic responses, thereby mimicking the renal responses observed in clinical conditions characterized by a low effective arterial volume such as congestive heart failure. Our objective was to evaluate the impact of angiotensin II receptor blockade with candesartan on the renal hemodynamic and urinary excretory responses to a progressive orthostatic stress in normal subjects. METHODS: Twenty healthy men were submitted to three levels of LBNP (0, -10, and -20 mbar or 0, -7.5, and -15 mm Hg) for 1 hour according to a crossover design with a minimum of 2 days between each level of LBNP. Ten subjects were randomly allocated to receive a placebo and ten others were treated with candesartan 16 mg orally for 10 days before and during the three levels of LBNP. Systemic and renal hemodynamics, renal sodium excretions, and the hormonal response were measured hourly before, during, and for 2 hours after LBNP. RESULTS: During placebo, LBNP induced no change in systemic and renal hemodynamics, but sodium excretion decreased dose dependently with higher levels of LBNP. At -20 mbar, cumulative 3-hour sodium balance was negative at -2.3 +/- 2.3 mmol (mean +/- SEM). With candesartan, mean blood pressure decreased (76 +/- 1 mm Hg vs. 83 +/- 3 mm Hg, candesartan vs. placebo, P < 0.05) and renal plasma flow increased (858 +/- 52 mL/min vs. 639 +/- 36 mL/min, candesartan vs. placebo, P < 0.05). Glomerular filtration rate (GFR) was not significantly higher with candesartan (127 +/- 7 mL/min in placebo vs. 144 +/- 12 mL/min in candesartan). No significant decrease in sodium and water excretion was found during LBNP in candesartan-treated subjects. At -20 mbar, the 3-hour cumulative sodium excretion was + 4.6 +/- 1.4 mmol in the candesartan group (P= 0.02 vs. placebo). CONCLUSION: Selective blockade of angiotensin II type 1 (AT1) receptors with candesartan increases renal blood flow and prevents the antinatriuresis during sustained lower body negative pressure despite a modest decrease in blood pressure. These results thus provide interesting insights into potential benefits of AT1 receptor blockade in sodium-retaining states such as congestive heart failure.