Differential phosphorylation, desensitization, and internalization of α1A-adrenoceptors activated by norepinephrine and oxymetazoline

Loss of response on repetitive drug exposure (i.e., tachyphylaxis) is a particular problem for the vasoconstrictor effects of medications containing oxymetazoline (OXY), an α1-adrenoceptor (AR) agonist of the imidazoline class. One cause of tachyphylaxis is receptor desensitization, usually accompanied by phosphorylation and internalization. It is well established that a1A-ARs are less phosphorylated, desensitized, and internalized on exposure to the phenethylamines norepinephrine (NE), epinephrine, or phenylephrine (PE) than are the a1B and a1D subtypes. However, here we show in human embryonic kidney-293 cells that the low-efficacy agonist OXY induces G protein-coupled receptor kinase 2-dependent a1A-AR phosphorylation, followed by rapid desensitization and internalization (∼40% internalization after 5 minutes of stimulation), whereas phosphorylation of α1A-ARs exposed to NE depends to a large extent on protein kinase C activity and is not followed by desensitization, and the receptors undergo delayed internalization (∼35% after 60 minutes of stimulation). Native α1A-ARs from rat tail artery and vas deferens are also desensitized by OXY, but not by NE or PE, indicating that thisproperty of OXY is not limited to recombinant receptors expressed in cell systems. The results of the present study are clearly indicative of agonist-directed a1A-AR regulation. OXY shows functional selectivity relative to NE and PE at a1A-ARs, leading to significant receptor desensitization and internalization, which is important in view of the therapeutic vasoconstrictor effects of this drug and the varied biologic process regulated by α1A-ARs. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics.

Evaluation of the presence of VEGF, BMP2 and CBFA1 proteins in autogenous bone graft: Histometric and immunohistochemical analysis

Aims: The purpose of this study was to evaluate the expression of proteins that participate in the osteoinduction stage (VEGF, BMP2 and CBFA1) of the process of bone regeneration of defects created in rat calvariae and filled with autogenous bone block grafts. Materials and methods: 10 adult male rats (Rattus norvegicus albinus, Wistar) were used, who received two bone defects measuring 5 mm each in the calvariae. The bone defects constituted two experimental groups (n = 10): Control Group (CONT) (defects filled with a coagulum); Graft Group (GR) (defects filled with autogenous bone removed from the contralateral defect). The animals were submitted to euthanasia at 7 and 30 days post-operatively. Results: Quantitative analysis demonstrated significantly greater bone formation in Group GR, but the presence of the studied proteins was significantly greater in the CONT Group in both time intervals of observation. Conclusion: It was not possible in this study in cortical bone block groups to detect the osteoinductive proteins in a significant amount during the repair process. © 2013 European Association for Cranio-Maxillo-Facial Surgery.

Horizontal ridge augmentation of the atrophic anterior maxilla using rhBMP-2/ACS or autogenous bone grafts: A proof-of-concept randomized clinical trial

Aim To compare the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge carrier (ACS) with autogenous bone graft for augmentation of the edentulous atrophic anterior maxilla. Methods Twenty-four subjects were enrolled in a randomized, controlled, parallel-group, open-label clinical trial. Subjects either received rhBMP-2/ACS (1.5 mg/ml) or particulated autogenous bone harvested from the mandibular retromolar region. A titanium-mesh was used to provide space and wound stability. A guide was used to standardize clinical recordings using an analogue caliper. Alveolar ridge width was also assessed using cone-beam computed tomography. Results rhBMP-2/ACS yielded significantly greater radiographic horizontal bone gain compared with autogenous bone graft at immediate subcrestal levels (1.5 ± 0.7 versus 0.5 ± 0.9 mm; p = 0.01); non-significant differences were observed at mid- (2.9 ± 0.8 versus 2.9 ± 0.9 mm; p = 0.98) and apical (1.7 ± 0.9 versus 1.8 ± 1.1 mm; p = 0.85) crestal levels. No significant differences in clinical horizontal bone gain were observed at 6 months between rhBMP-2/ACS and autogenous bone graft (3.2 ± 0.9 mm versus 3.7 ± 1.4 mm; p = 0.31). Sixty-two implants were placed after 6 month of healing with no significant differences between groups for number of implants, implant size, primary stability and survival. Conclusions rhBMP-2/ACS appears a realistic alternative for augmentation of the edentulous atrophic anterior maxilla. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Avaliação ex vivo da expressão de TLR-2 e TLR-4 em leucócitos de equinos e sua relação com a tolerância à endotoxina

Pós-graduação em Ciência Animal - FMVA

Exigências nutricionais de cabritas saanen em crescimento dos 30 aos 45 kg

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Mananoligossacarídeo e β-glucano na suplementação dietária para juvenis de tilápia-do-nilo mantidos em tanques-rede

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influência do treinamento físico intervalado nas pressões respiratórias na concentração de nitrito/nitrato e do receptor de leptina solúvel em mulheres na pós-menopausa

Pós-graduação em Ciências da Motricidade - IBRC

Identificação de proteínas ligantes de CRABP2, proteína envolvida na via de sinalização celular por ácido retinóico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estimativa das exigências de treonina, lisina e metionina+cistina para frangas de postura por meio de modelos

Pós-graduação em Zootecnia - FCAV

Protective effect of gamma-tocopherol-enriched diet on N-methyl-N-nitrosourea-induced epithelial dysplasia in rat ventral prostate

Despite recent advances in understanding the biological basis ofprostate cancer (PCa), the management of this disease remains a challenge. Chemoprotective agents have been usedto protect against or eradicateprostatemalignancies. Here, we investigated the protective effect of -tocopherol on N-methyl-N-nitrosourea (MNU)-induced epithelial dysplasia in the rat ventral prostate (VP). Thirty-two male Wistar rats were divided into four groups (n=8): control (CT): healthy control animals fed a standard diet; control+-tocopherol (CT+T): healthy control animals without intervention fed a -tocopherol-enriched diet (20mg/kg); N-methyl-N-nitrosourea (MNU): rats that received a single dose of MNU (30mg/kg) plus testosterone propionate (100mg/kg) and were fed a standard diet; and MNU+-tocopherol (MNU+T): rats that received the same treatment of MNU plus testosterone and were fed with a -tocopherol-enriched diet (20mg/kg). After 4months, the VPs were excised to evaluate morphology, cell proliferation and apoptosis, as well as cyclooxygenase-2 (Cox-2), glutathione-S-transferase-pi (GST-pi) and androgen receptor (AR) protein expression, and matrix metalloproteinase-9 (MMP-9) activity. An increase in the incidence of epithelial dysplasias, such as stratified epithelial hyperplasia and squamous metaplasia, in the MNU group was accompanied by augmented cell proliferation, GST-pi and Cox-2 immunoexpression and pro-MMP-9 activity. Stromal thickening and inflammatory foci were also observed. The administration of a -tocopherol-enriched diet significantly attenuated the adverse effects of MNU in the VP. The incidence of epithelial dysplasia decreased, along with the cell proliferation index, GST-pi and Cox-2 immunoexpression. The gelatinolytic activity of pro-MMP-9 returned to the levels observed for the CT group. These results suggest that -tocopherol acts as a protective agent against MNU-induced prostatic disorders in the rat ventral prostate.

Análise do potencial osteogênico de células estromais derivadas da medula óssea de ratas adultas e senis submetidas ou não ao treinamento de força

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of Avocado/Soybean Unsaponifiables on Osseointegration: A Proof-of-Principle Preclinical In Vivo Study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Energy and protein requirements of male and female saanen goats

Pós-graduação em Zootecnia - FCAV

Reparo ósseo dedefeitos de tamanho crítico tratados com aspirado de medula óssea associado ou não a terapia com laser em baixa intensidade: estudo imunoistoquímico em calvárias de ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Caracterização de osteoblastos diferenciados de células-tronco mesenquimais da medula óssea de ratos espontâneamente hipertensos (SHR)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)