IMPACTOS DA CULTURA ORGANIZACIONAL NA OPERACIONALIZAÇÃO DOS PROCESSOS DE PROGRESSÃO FUNCIONAL DA ESCOLA DE DANÇA DA UFBA

Este artigo, a partir da concepção da importância crescente de mais bem se estudar diferentes aspectos da gestão do ensino superior, tem por questão de pesquisa: Quais os impactos da cultura organizacional na operacionalização dos processos de progressão funcional docente no NAC da UFBA, no período de 2009-2013? A pesquisa de campo foi feita através de entrevista estruturada com 5 docentes de perfil diverso do citado núcleo, sendo sempre que possível trazidas suas falas integrais como forma de permitir ao leitor um conhecimento mais detalhado de suas percepções em relação aos aspectos explorados. Como principais achados das entrevistas confirmaram-se os pressupostos teóricos trazidos em autores a exemplo de Rorato e Dias (2011), Marra e Melo (2005), Zago (2000), Macedo e Pires (2006), da predominância do modelo cultural burocrático e categorizado como modelo Apolo nas organizações públicas em geral e nas IFES no particular. Sugere-se a continuidade deste estudo com a realização de trabalhos que ampliem esta pesquisa na própria UFBA e em outras IES localizadas no país

VISÃO E COMPORTAMENTO ORGANIZACIONAL: UM ESTUDO EXPLORATÓRIO

A visão é uma mensagem empresarial daquilo que os diretores e funcionários aspiram sobre a empresa, direcionando os funcionários e delimitando comportamentos que tornam-se essenciais. O presente estudo, objetivou constatar a existência da visão em uma organização, bem como, detectar o planejamento e envolvimento dos funcionários na definição dessa visão. Neste estudo foram realizadas duas entrevistas estruturadas: com o diretor proprietário e dois funcionários, em uma empresa de autopeças da região do Alto Uruguai – (RS). Verificou-se, desta forma, que a empresa tem uma visão definida e, em conseqüência, os funcionários estabelecem metas a serem cumpridas, adotam comportamentos adequados a fim de alcançar os objetivos traçados pela empresa, orientando, então, a um único rumo.-Vision is an enterprising message of what managers and employees aspire to the enterprise, guiding the employees and delimiting attitudes which become essential. The present paper aims at verifying the existence of vision in an organization, as well as the planning and involvement of employees in defining this vision. Interviews were carried out: with the manager and two employees in a hardware enterprise of Alto Uruguai region – (RS). It was noticed, this way, that the enterprise has a defined vision and, consequently, the employees establish goals to be fultilled and adopt proper behavior in order to reach the objectives projected by enterprise, orienting to a common course

Improvement in hemodynamic performance, exercise capacity, inflammatory profile, and left ventricular reverse remodeling after intracoronary delivery of mesenchymal stem cells in an experimental model of pressure overload hypertrophy

ObjectivesIn a rat model of pressure overload hypertrophy, we studied the effects of intracoronary delivery of mesenchymal stem cells on hemodynamic performance, exercise capacity, systemic inflammation, and left ventricular reverse remodeling.MethodsSprague–Dawley rats underwent aortic banding and were followed up by echocardiographic scanning. After a decrease in fractional shortening of 25% from baseline, animals were randomized to intracoronary injection of mesenchymal stem cells (MSC group; n = 28) or phosphate-buffered saline solution (control group; n = 20). Hemodynamic and echocardiographic assessment, swim testing to exhaustion, and measurement of inflammatory markers were performed before the rats were humanely killed on postoperative day 7, 14, 21, or 28.ResultsInjection of mesenchymal stem cells improved systolic function in the MSC group compared with the control group (mean ± standard deviation: maximum dP/dt 3048 ± 230 mm Hg/s vs 2169 ± 97 mm Hg/s at 21 days and 3573 ± 741 mm Hg/s vs 1363 ± 322 mm Hg/s at 28 days: P < .001). Time to exhaustion was similarly increased in the MSC group compared with controls (487 ± 35 seconds vs 306 ± 27 seconds at 28 days; P < .01). Serum levels of interleukins 1 and 6, tumor necrosis factor–alpha, and brain natriuretic peptide-32 were significantly decreased in animals treated with mesenchymal stem cells. Stem cell transplantation improved left ventricular fractional shortening at 21 and 28 days. Left ventricular end-systolic and end-diastolic diameters were also improved at 28 days.ConclusionsIn this model of pressure overload hypertrophy, intracoronary delivery of mesenchymal stem cells during heart failure was associated with an improvement in hemodynamic performance, maximal exercise tolerance, systemic inflammation, and left ventricular reverse remodeling. This study suggests a potential role of this treatment strategy for the management of hypertrophic heart failure resulting from pressure overload

The thyroid hormone triiodothyronine controls macrophage maturation and functions: protective role during inflammation.

The endocrine system participates in regulating macrophage maturation, although little is known about the modulating role of the thyroid hormones. In vitro results demonstrate a negative role of one such hormone, triiodothyronine (T 3 ), in triggering the differentiation of bone marrow–derived monocytes into unpolarized macrophages. T 3 -induced macrophages displayed a classically activated (M1) signature. A T 3 -induced M1-priming effect was also observed on polarized macrophages because T 3 reverses alternatively activated (M2) activation, whereas it enhances that of M1 cells. In vivo , circulating T 3 increased the content of the resident macrophages in the peritoneal cavity, whereas it reduced the content of the recruited monocyte-derived cells. Of interest, T 3 significantly protected mice against endotoxemia induced by lipopolysaccharide i.p. injection; in these damaged animals, decreased T 3 levels increased the recruited (potentially damaging) cells, whereas restoring T 3 levels decreased recruited and increased resident (potentially beneficial) cells. These data suggest that the anti-inflammatory effect of T 3 is coupled to the modulation of peritoneal macrophage content, in a context not fully explained by the M1/M2 framework. Thyroid hormone receptor expression analysis and the use of different thyroid hormone receptor antagonists suggest thyroid hormone receptor β1 as the major player mediating T 3 effects on macrophages. The novel homeostatic link between thyroid hormones and the pathophysiological role of macrophages opens new perspectives on the interactions between the endocrine and immune systems

Novel Approaches to Improve Myeloma Cell Killing by Monoclonal Antibodies

The monoclonal antibodies (mAbs) have significantly changed the treatment of multiple myeloma (MM) patients. However, despite their introduction, MM remains an incurable disease. The mAbs currently used for MM treatment were developed with different mechanisms of action able to target antigens, such as cluster of differentiation 38 (CD38) and SLAM family member 7 (SLAMF7) expressed by both, MM cells and the immune microenvironment cells. In this review, we focused on the mechanisms of action of the main mAbs approved for the therapy of MM, and on the possible novel approaches to improve MM cell killing by mAbs. Actually, the combination of anti-CD38 or anti-SLAMF7 mAbs with the immunomodulatory drugs significantly improved the clinical effect in MM patients. On the other hand, pre-clinical evidence indicates that different approaches may increase the efficacy of mAbs. The use of trans-retinoic acid, the cyclophosphamide or the combination of anti-CD47 and anti-CD137 mAbs have given the rationale to design these types of combinations therapies in MM patients in the future. In conclusion, a better understanding of the mechanism of action of the mAbs will allow us to develop novel therapeutic approaches to improve their response rate and to overcome their resistance in MM patients

PROTEASOME INHIBITORS MODULATE OSTEOCYTE DEATH AND AUTOPHAGY IN MULTIPLE MYELOMA.

Background: Cell death and autophagy are the main cellular processes involved in the regulation of bone remodeling by osteocytes. Recently we have demonstrated that an increased osteocyte death is involved in multiple myeloma (MM)-induced osteolysis through the upregulation of osteoclast recruitment. Aims: Because proteasome inhibitors including Bortezomib (BOR) are known to be able to target osteoblasts in this study we have investigated the potential effect of these drugs on osteocytes and their cell death and autophagy. Methods: Firstly the effect of the proteasome inhibitors BOR and MG262 on osteocyte viability was evaluated in vitro in murine osteocytic cell line MLO-Y4 and in the human pre-osteocytic one HOB-01. Both cell lines were co-coltured for 48 hours in the presence or absence of the human myeloma cell lines (HMCLs) RPMI8226 and JJN3, placed in a transwell insert in the presence or the absence of BOR or MG262. Moreover the effect of proteasome inhibitors on dexamethasone (DEX)-induced MLO-Y4 death, obtained at high doses (10-5-10-6M), was checked in combination with PTH(1-34). To evaluate the presence of autophagy and apoptosis in osteocytes, we checked the expression of both autophagic marker LC3 and apoptotic marker APAF-1 by confocal microscopy in the co-colture system with MLO-Y4 and RPMI-8226. Finally we performed a retrospective histological evaluation on bone biopsies of a cohort of 31 newly diagnosis MM underwent to different treatments including BOR-based regimen. Bone biopsies were obtained at the diagnosis and after an average time of 12 months of treatment. Osteocyte viability was evaluated in a total of 500 lacunae per histological sections. Results: The in vitro treatment with BOR or MG262 significantly blunted MLO-Y4 and HOB-01 cell death. Similarly, DEXinduced MLO-Y4 death was reduced by proteasome inhibitors. Interestingly, we found that both proteasome inhibitors potentiated the PTH (1-34) short-term effects on DEX-induced osteocyte death. Prevalence of autophagic cell death compared to apoptosis was observed in this system. In line with these data, we showed that neither the HMCLs nor treatment with DEX increase the apoptotic death and caspase 3 activation in both MLO-Y4 and HOB-01 cell lines. BOR treatment increased the basal level of LC3 indicating a pro-survival and protective function of autophagy against the BOR-induce stress. On the contrary, when the cells undergo to a stronger stress such as in the presence of HMCLs or by treatment with high dose of DEX we found that both proteasome inhibitors blocked autophagic cell death in osteocytes. In the in vivo study we found a significant increase of the number of viable osteocytes in MM patients treated with BOR-based regimen as compared to those treated without BOR (% median increase: +6% vs. +1.30%; p=0.017). Patients treated with BOR alone showed the highest increase of osteocyte viability, as compared to those either treated without BOR (+11.6% vs. +1.3%, p=0.0019) or treated with BOR plus DEX (+11.6% vs. +4.4%, p=0.01). On the other hand, any significant difference was not observed in patients treated with Thalidomide (THAL) or Immunomodulatory drugs (IMiDs) than in those untreated with these drugs (p= 0.7). A multiple regression non-parametric analysis showed that BOR had a significant positive impact on osteocyte viability (p=0.042) whereas THAL/IMiDs as well as Zoledronic acid (ZOL) treatments have not (p=0.2). BOR also counterbalanced the negative effect of DEX treatment (p=0.035). Summary/Conclusion: Our data suggest that proteasome inhibitors blunted osteocyte cell death induced by MM cells and DEX through the modulation of the autophagy and potentiated the effect of PTH. Overall our in vitro and in vivo data support the use of BOR to improve bone integrity in MM patients

Myeloma-Induced Osteocyte Death Was Blunted By Proteasome Inhibitors Through The Modulation Of Autophagy

Osteocytes are critical in the maintenance of bone integrity regulating bone remodeling through the cell death and autophagy, a cellular process stress-induced to prolong cell survival but when induced excessively can cause cell death. Recently we have demonstrated that an increased osteocyte death is involved in multiple myeloma (MM)-induced osteolysis. However the mechanisms involved in this process as well as the effect of the proteasome inhibitors able to stimulate bone formation are not known and have been investigated in this study. Firstly the effect of the proteasome inhibitors BOR and MG262 on osteocyte viability was evaluated in vitro in murine osteocytic cell line MLO-Y4 and in the human pre-osteocytic one HOB-01. Both cell lines were co-coltured for 48 hours in the presence or absence of the human myeloma cell lines (HMCLs) RPMI8226 and JJN3, placed in a traswell insert. The treatment for 12-24 hours with (BOR) (2nM) and MG262 (10nM) significantly blunted MLO-Y4 and HOB-01 cell death. In addition, dexamethasone (DEX)-induced MLO-Y4 apoptosis, obtained at high doses (10-5-10-6 M), was reduced by the treatment with proteasome inhibitors. Interestingly, we found that PTH short-term treatment potentiated the in vitro effects of proteasome inhibitors on DEX-induced osteocyte death. To evaluate the presence of autophagy in osteocytes, we checked the expression of the autophagic marker LC3 both by confocal microscopy and western blot analysis in the co-colture system with MLO-Y4 and RPMI-8226. Prevalence of autophagic cell death and in a lesser extent apoptosis was observed in this system. BOR increased the basal level of LC3 indicating a pro-survival and protective function of autophagy against the BOR-induce stress. On the contrary, when cells undergo to a stronger stress such as in the presence of HMCLs or by treatment with high dose of DEX we found that both proteasome inhibitors BOR and MG262 blocked autophagic cell death in osteocytes. To translate our in vitro evidence in a clinical perspective, thereafter we performed a histological evaluation on bone biopsies of a cohort of 37 newly diagnosis MM patients 31 of them with symptomatic MM and 6 with smoldering MM (SMM). The 55% of patients with MM have evidence of osteolytic lesions at the X-rays survey. Bone biopsies were obtained at the diagnosis and after an average time of 12 months of treatment or observation. Osteocyte viability was evaluated in a total of 500 lacunae per histological sections. A significant increase of the number of viable osteocytes was demonstrated in MM patients treated with BOR-based regimen as compared to those treated without BOR (% median increase: +6% vs. +1.30%; p=0.017). Patients treated with BOR alone showed the highest increase of osteocyte viability, as compared to those either treated without BOR (+11.6% vs. +1.3%, p=0.0019) or treated with BOR plus DEX (+11.6% vs. +4.4%, p=0.01). A reduction of both osteocyte apoptosis and autophagy was demonstrated by TUNEL assays and confocal microscopy. On the other hand, any significant difference was not observed in patients treated with Thalidomide (THAL) or Immunomodulatory drugs (IMiDs) than in those untreated with these drugs (p= 0.7). A multiple regression non-parametric analysis showed that BOR had a significant positive impact on osteocyte viability (p=0.042) whereas THAL/IMiDs as well as Zoledronic acid (ZOL) treatments have not (p=0.2). BOR also counterbalanced the negative effect of DEX treatment (p=0.035). Our data suggest that proteasome inhibitors blunted osteocyte cell death induced by MM cells and DEX through the modulation of the autophagy supporting their use to improve bone integrity in MM patients

Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling

Multiple myeloma (MM) is characterized by a high capacity to induce alterations in the bone remodeling process. The increase in osteoclastogenesis and the suppression of osteoblast formation are both involved in the pathophysiology of the bone lesions in MM. The proteasome inhibitor (PI) bortezomib is the first drug designed and approved for the treatment of MM patients by targeting the proteasome. However, recently novel PIs have been developed to overcome bortezomib resistance. Interestingly, several preclinical data indicate that the proteasome complex is involved in both osteoclast and osteoblast formation. It is also evident that bortezomib either inhibits osteoclast differentiation induced by the receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) or stimulates the osteoblast differentiation. Similarly, the new PIs including carfilzomib and ixazomib can inhibit bone resorption and stimulate the osteoblast differentiation. In a clinical setting, PIs restore the abnormal bone remodeling by normalizing the levels of bone turnover markers. In addition, a bone anabolic effect was described in responding MM patients treated with PIs, as demonstrated by the increase in the osteoblast number. This review summarizes the preclinical and clinical evidence on the effects of bortezomib and other new PIs on myeloma bone disease