Sol-gel Er-doped SiO(2)-HfO(2) planar waveguides: A viable system for 1.5 mu m application

70SiO(2)-30HfO(2) planar waveguides, doped with Er(3+) concentrations ranging from 0.3 to 1 mol %, were prepared by sol-gel route, using dip-coating deposition on silica glass substrates. The waveguides show high densification degree, effective intermingling of the two components of the film, and uniform surface morphology. Propagation losses of about 1 dB/cm were measured at 632.8 nm. When pumped with 987 or 514.5 nm continuous-wave laser light, the waveguides show the (4)I(13/2)-->(4)I(15/2) emission band with a bandwidth of 48 nm. The spectral features are found independent both on erbium content and excitation wavelength. The (4)I(13/2) level decay curves presented a single-exponential profile, with a lifetime between 2.9 and 5.0 ms, depending on the erbium concentration. (C) 2002 American Institute of Physics.

NOVEL EVIDENCE THAT BETA-ADRENOCEPTORS OF THE MEDIAL SEPTAL AREA REGULATE BLOOD-PRESSURE AND ELECTROLYTE BALANCE

We investigated the participation of the beta-adrenoceptors of the septal area (SA) in sodium and potassium excretion and urine flow. The alterations in arterial pressure and some renal functions were also investigated. The injection of 2.10(-9) to 16.10(-9)M of isoproterenol, through a cannula permanently implanted into the SA produced a significant dose-dependent decrease in urinary Na+ and K+ excretion and urinary flow. Pretreatment with 16.10(-9) M butoxamine antagonized the effect of 4.10(-9) M isoproterenol but pretreatment with 16.10(-9) M practolol did not abolish the effect of isoproterenol. The beta 2-agonist terbutaline and salbutamol (4.10(-9) M when injected intraseptally also caused a decrease in urine flow and in renal Na+ and K+ excretion. After injection of isoproterenol or salbutamol (4.10(-9) M) into the SA, the arterial pressure, glomerular, filtration rate (GFR) and filtered Nd were reduced while Na+ fractional reabsorption was increased. The results indicate that the beta 2-adrenoceptors of the SA play a role in the decrease of Na+, K+ and urine flow and this effect may be due to a drop in GFR and filtered Na+ and to the rise in tubular Na+ reabsorption.

Atypical beta-adrenoceptor subtypes mediate relaxations of rabbit corpus cavernosum

This study was performed to characterize the beta-adrenoceptor population in rabbit isolated corpus cavernosum (RbCC) by using nonselective and selective beta-adrenoceptor agonists and antagonists in functional assays. Metaproterenol, ritodrine, fenoterol, and 8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(rho-methoxy-phenyl)1-methylethyl] amino] ethyl] carbostyril (TA 2005) (3-100 nmol each) dose dependently relaxed the RbCC preparations. These relaxations were markedly reduced by N-omega-nitro-L-arginine methyl ester (L-NAME; 10 muM) and 1H-[1,2,4]-oxadiazolo-[4,3,-a]quinoxalin-1-one (ODQ) (10 muM), whereas the adenylyl cyclase inhibitor SQ 22,536 [9-(2-tetrahydrofuryl)adenine] (10 muM) had no effect. In contrast, neither L-NAME nor ODQ affected the isoproterenol-induced RbCC relaxations, but SQ 22,536 abolished this response. Sildenafil (1 muM) significantly potentiated the relaxations induced by beta(2)-agonists without affecting the isoproterenol-evoked relaxations. Rolipram (10 muM) enhanced the relaxations elicited by isoproterenol but had no effect on those induced by the selective beta(2) agonists. Propranolol and (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanolhydrochloride (ICI 118,551) determined a rightward shift in the concentration-response curves to isoproterenol in a noncompetitive manner with a reduction of maximum response at the highest antagonist concentration, with the slope values significantly different from unity. Propranolol and ICI 118,551 had no effect on the relaxations elicited by fenoterol, TA 2005, metaproterenol, and ritodrine. Atenolol and 1-[2-((3-carbamoyl-4-hydroxy)phenoxy) ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]2-propanol methanesulfonate (CGP 20712A) (0.1-10 muM) failed to affect the relaxations induced by all tested beta-adrenoceptor agonists. Our study revealed the existence of two atypical beta-adrenoceptors in the rabbit erectile tissue. Isoproterenol relaxes the rabbit cavernosal tissue by activating atypical beta-adrenoceptors coupled to adenylyl cyclase pathway, whereas the selective beta2-adrenoceptor agonists relax the RbCC tissue through another atypical beta-adrenoceptor subtype coupled to nitric oxide release from the sinusoidal endothelium.

Cross-talk with β2-adrenoceptors enhances ligand affinity properties from endothelial alpha1D-adrenoceptors that mediates carotid relaxation

Objectives Our main objectives were to investigate the affinity properties of endothelial and muscular α1D-adrenoceptors and to characterize the cross-talk between endothelial α1D- adrenoceptors and β2-adrenoceptors in rat carotid. Methods Relaxation and contraction concentration-response curves for phenylephrine (α1-adrenergic agonist) were obtained in carotid rings in absence or presence of increasing concentrations of BMY7378 (α 1D-adrenergic antagonist), combined or not with increasing concentration of ICI-118,551 (β2-adrenergic antagonist). Schild analysis was used to estimate the affinity constant from pA2 values of BMY7378. Key Findings BMY7378 produced an unsurmountable antagonism on phenylephrine-induced relaxation but a surmountable antagonism on phenylephrine-induced contraction. BMY7378 potency was higher in inhibiting the relaxation than the contraction induced by phenylephrine because the rightward shifts induced by BMY7378 were greater in the relaxation. The apparent pA 2 value for BMY7378 in phenylephrine-induced relaxation was greater than in contraction. When combined with ICI-118,551, BMY7378 yielded a surmountable antagonism on phenylephrine-induced relaxation and presented a pA2 value similar to that obtained in phenylephrine-induced contraction. Conclusions Endothelial α1D-adrenoceptors, which mediates rat carotid relaxation, present high ligand affinity because of the cross-talk with β2-adrenoceptors, which explains the higher potency of phenylephrine in inducing relaxation than contraction and the atypical unsurmountable antagonism produced by BMY7378 on phenylephrine-induced relaxation. © 2013 Royal Pharmaceutical Society.

Erythrina mulungu Alkaloids Are Potent Inhibitors of Neuronal Nicotinic Receptor Currents in Mammalian Cells

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Analytic perturbation theory for bound states in the transfer matrix spectrum of weakly correlated lattice ferromagnetic spin systems

We consider general d-dimensional lattice ferromagnetic spin systems with nearest neighbor interactions in the high temperature region ('beta' << 1). Each model is characterized by a single site apriori spin distribution taken to be even. We also take the parameter 'alfa' = ('S POT.4') - 3 '(S POT.2') POT.2' > 0, i.e. in the region which we call Gaussian subjugation, where ('S POT.K') denotes the kth moment of the apriori distribution. Associated with the model is a lattice quantum field theory known to contain a particle of asymptotic mass -ln 'beta' and a bound state below the two-particle threshold. We develop a 'beta' analytic perturbation theory for the binding energy of this bound state. As a key ingredient in obtaining our result we show that the Fourier transform of the two-point function is a meromorphic function, with a simple pole, in a suitable complex spectral parameter and the coefficients of its Laurent expansion are analytic in 'beta'.

Clenbuterol suppresses proteasomal and lysosomal proteolysis and atrophy-related genes in denervated rat soleus muscles independently of Akt

Goncalves DA, Silveira WA, Lira EC, Gra a FA, Paula-Gomes S, Zanon NM, Kettelhut IC, Navegantes LC. Clenbuterol suppresses proteasomal and lysosomal proteolysis and atrophy-related genes in denervated rat soleus muscles independently of Akt. Am J Physiol Endocrinol Metab 302: E123-E133, 2012. First published September 27, 2011; doi:10.1152/ajpendo.00188.2011.-Although it is well known that administration of the selective beta(2)-adrenergic agonist clenbuterol (CB) protects muscle following denervation (DEN), the underlying molecular mechanism remains unclear. We report that in vivo treatment with CB (3 mg/kg sc) for 3 days induces antiproteolytic effects in normal and denervated rat soleus muscle via distinct mechanisms. In normal soleus muscle, CB treatment stimulates protein synthesis, inhibits Ca(2+)-dependent proteolysis, and increases the levels of calpastatin protein. On the other hand, the administration of CB to DEN rats ameliorates the loss of muscle mass, enhances the rate of protein synthesis, attenuates hyperactivation of proteasomal and lysosomal proteolysis, and suppresses the transcription of the lysosomal protease cathepsin L and of atrogin-1/MAFbx and MuRF1, two ubiquitin (Ub) ligases involved in muscle atrophy. These effects were not associated with alterations in either IGF-I content or Akt phosphorylation levels. In isolated muscles, CB (10(-6) M) treatment significantly attenuated DEN-induced overall proteolysis and upregulation in the mRNA levels of the Ub ligases. Similar responses were observed in denervated muscles exposed to 6-BNZ-cAMP (500 mu M), a PKA activator. The in vitro addition of triciribine (10 mu M), a selective Akt inhibitor, did not block the inhibitory effects of CB on proteolysis and Ub ligase mRNA levels. These data indicate that short-term treatment with CB mitigates DEN-induced atrophy of the soleus muscle through the stimulation of protein synthesis, downregulation of cathepsin L and Ub ligases, and consequent inhibition of lysosomal and proteasomal activities and that these effects are independent of Akt and possibly mediated by the cAMP/PKA signaling pathway.

beta-ADRENOCEPTORS IN THE MEDIAL AMYGDALOID NUCLEUS MODULATE THE TACHYCARDIAC RESPONSE TO RESTRAINT STRESS IN RATS

In the present study, we investigated the involvement of beta-adrenoceptors in the medial amygdaloid nucleus (MeA) in cardiovascular responses evoked in rats submitted to an acute restraint stress. We first pretreated Wistar rats with the nonselective beta-adrenoceptor antagonist propranolol microinjected bilaterally into the MeA (10, 15, and 20 nmol/100 nL) 10 min before exposure to acute restraint. The pretreatment with propranolol did not affect the blood pressure (BP) increase evoked by restraint. However, it increased the tachycardiac response caused by acute restraint when animals were pretreated with a dose of 15 nmol, without a significant effect on the BP response. This result indicates that beta-adrenoceptors in the MeA have an inhibitory influence on restraint-evoked heart rate (HR) changes. Pretreatment with the selective beta(2)-adrenoceptor antagonist ICI 118,551 (10, 15, and 20 nmol/100 nL) significantly increased the restraint-evoked tachycardiac response after doses of 15 and 20 nmol, an effect that was similar to that observed after the pretreatment with propranolol at a dose of 15 nmol, without a significant effect on the BP response. Pretreatment of the MeA with the selective beta(1)-adrenoceptor antagonist CGP 20712 (10, 15, and 20 nmol/100 nL) caused an opposite effect on the HR response, and a significant decrease in the restraint-evoked tachycardia was observed only after the dose of 20 nmol, without a significant effect on the BP response. Because propranolol is an equipotent antagonist of both beta(1) and beta(2)-adrenoceptors, and opposite effects were observed after the treatment with the higher doses of the selective antagonists ICI 118,551 and CGP 20712, the narrow window in the dose-response to propranolol could be explained by a functional antagonism resulting from the simultaneous inhibition of beta(1) and beta(2)-adrenoceptors by the treatment with propranolol. The present results suggest that beta(2)-adrenoceptors have an inhibitory influence on the restraint-evoked tachycardiac response, whereas beta(1)-adrenoceptors have a facilitatory influence on the restraint-evoked tachycardiac response. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Flow Boiling Characteristics for R1234ze(E) in 1.0 and 2.2 mm Circular Channels

Experimental flow boiling heat transfer results are presented for horizontal 1.0 and 2.2 mm I. D. (internal diameter) stainless steel tubes for tests with R1234ze(E), a new refrigerant developed as a substitute for R134a with a much lower global warming potential (GWP). The experiments were performed for these two tube diameters in order to investigate a possible transition between macro and microscale flow boiling behavior. The experimental campaign includes mass velocities ranging from 50 to 1500 kg/m(2) s, heat fluxes from 10 to 300 kW/m(2), exit saturation temperatures of 25, 31 and 35 degrees C, vapor qualities from 0.05 to 0.99 and heated lengths of 180 mm and 361 mm. Flow pattern characterization was performed using high speed videos. Heat transfer coefficient, critical heat flux and flow pattern data were obtained. R1234ze(E) demonstrated similar thermal performance to R134a data when running at similar conditions. [DOI: 10.1115/1.4004933]

Amygdala gene expression of NMDA and GABAA receptors in patients with mesial temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and affects 40% of the patients. Seizures arising from the mesial temporal lobe structures (i.e., amygdala and hippocampus) are common, whereas neocortical seizures are rare. In recent years, many studies aimed to identify the pattern of gene expression of neurotransmitters involved in molecular mechanisms of epilepsy. We used real-time PCR to quantify the expression of GABAA (subunits a1, beta 1, beta 2) and NMDA (subunits NR1, NR2A, and NR2B) receptor genes in amygdalae of 27 patients with TLE and 14 amygdalae from autopsy controls. The NR1 subunit was increased in patients with epilepsy when compared with controls. No differences were found in expression of NMDA subunits NR2A and NR2B or in a1, beta 1, and beta 2 subunits of GABAA receptors. Our results suggest that the NR1 subunit of NMDA receptors is involved in the amygdala hyperexcitability in some of the patients with TLE. (C) 2010 Wiley Periodicals, Inc., Inc.

Gastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophils

Neutrophil migration to inflamed sites is crucial for both the initiation of inflammation and resolution of infection, yet these cells are involved in perpetuation of different chronic inflammatory diseases. Gastrin-releasing peptide (GRP) is a neuropeptide that acts through G protein coupled receptors (GPCRs) involved in signal transmission in both central and peripheral nervous systems. Its receptor, gastrin-releasing peptide receptor (GRPR), is expressed by various cell types, and it is overexpressed in cancer cells. RC-3095 is a selective GRPR antagonist, recently found to have antiinflammatory properties in arthritis and sepsis models. Here we demonstrate that i.p. injection of GRP attracts neutrophils in 4 h, and attraction is blocked by RC-3095. Macrophage depletion or neutralization of TNF abrogates GRP-induced neutrophil recruitment to the peritoneum. In vitro, GRP-induced neutrophil migration was dependent on PLC-beta 2, PI3K, ERK, p38 and independent of G alpha i protein, and neutrophil migration toward synovial fluid of arthritis patients was inhibited by treatment with RC-3095. We propose that GRPR is an alternative chemotactic receptor that may play a role in the pathogenesis of inflammatory disorders.

Peptidomic Analysis of HEK293T Cells: Effect of the Proteasome Inhibitor Epoxomicin on Intracellular Peptides

Peptides derived from cytosolic, mitochondrial, and nuclear proteins have been detected in extracts of animal tissues and cell lines. To test whether the proteasome is involved in their formation, HEK293T cells were treated with epoxomicin (0.2 or 2 mu M) for 1 h and quantitative peptidomics analysis was performed. Altogether, 147 unique peptides were identified by mass spectrometry sequence analysis. Epoxomicin treatment decreased the levels of the majority of intracellular peptides, consistent with inhibition of the proteasome beta-2 and beta-5 subunits. Treatment with the higher concentration of epoxomicin elevated the levels of some peptides. Most of the elevated peptides resulted from cleavages at acidic residues, suggesting that epoxomicin increased the processing of proteins through the beta-1 subunit. Interestingly, some of the peptides that were elevated by the epoxomicin treatment had hydrophobic residues in P1 cleavage sites. Taken together, these findings suggest that, while the proteasome is the major source of intracellular peptides, other peptide-generating mechanisms exist. Because intracellular peptides are likely to perform intracellular functions, studies using proteasome inhibitors need to be interpreted with caution, as it is possible that the effects of these inhibitors are due to a change in the peptide levels rather than inhibition of protein degradation.

Both alpha(1)- and beta(1)-adrenoceptors in the bed nucleus of the stria terminalis are involved in the expression of conditioned contextual fear

BACKGROUND AND PURPOSE The bed nucleus of the stria terminalis (BNST) is a limbic structure that is involved in the expression of conditioned contextual fear. Among the numerous neural inputs to the BNST, noradrenergic synaptic terminals are prominent and some evidence suggests an activation of this noradrenergic neurotransmission in the BNST during aversive situations. Here, we have investigated the involvement of the BNST noradrenergic system in the modulation of behavioural and autonomic responses induced by conditioned contextual fear in rats. EXPERIMENTAL APPROACH Male Wistar rats with cannulae bilaterally implanted into the BNST were submitted to a 10 min conditioning session (6 footshocks, 1.5 ma/ 3 s). Twenty-four hours later freezing and autonomic responses (mean arterial pressure, heart rate and cutaneous temperature) to the conditioning box were measured for 10 min. The adrenoceptor antagonists were administered 10 min before the re-exposure to the aversive context. KEY RESULTS L-propranolol, a non-selective beta-adrenoceptor antagonist, and phentolamine, a non-selective a-adrenoceptor antagonist, reduced both freezing and autonomic responses induced by aversive context. Similar results were observed with CGP20712, a selective beta 1-adrenoceptor antagonist, and WB4101, a selective a1-antagonist, but not with ICI118,551, a selective beta 2-adrenoceptor antagonist or RX821002, a selective a2-antagonist. CONCLUSIONS AND IMPLICATIONS These findings support the idea that noradrenergic neurotransmission in the BNST via a1- and beta 1-adrenoceptors is involved in the expression of conditioned contextual fear.

Functional coupling of sensorimotor and associative areas during a catching ball task: a qEEG coherence study

Abstract Background Catching an object is a complex movement that involves not only programming but also effective motor coordination. Such behavior is related to the activation and recruitment of cortical regions that participates in the sensorimotor integration process. This study aimed to elucidate the cortical mechanisms involved in anticipatory actions when performing a task of catching an object in free fall. Methods Quantitative electroencephalography (qEEG) was recorded using a 20-channel EEG system in 20 healthy right-handed participants performed the catching ball task. We used the EEG coherence analysis to investigate subdivisions of alpha (8-12 Hz) and beta (12-30 Hz) bands, which are related to cognitive processing and sensory-motor integration. Results Notwithstanding, we found the main effects for the factor block; for alpha-1, coherence decreased from the first to sixth block, and the opposite effect occurred for alpha-2 and beta-2, with coherence increasing along the blocks. Conclusion It was concluded that to perform successfully our task, which involved anticipatory processes (i.e. feedback mechanisms), subjects exhibited a great involvement of sensory-motor and associative areas, possibly due to organization of information to process visuospatial parameters and further catch the falling object.