Qualidade de vida no trabalho nivel de estresse dos profissionais das UBS do Distrito Leste do Município de Foz do Iguaçu-PR

Trabalho de conclusão de Residência apresentado ao Programa Multiprofissional em Saúde da Família da Universidade Federal da Integração Latino-Americana, como requisito para obtenção do título de Especialista em Saúde da Família na modalidade de Residência. Orientador: Prof. Dr Thiago Luis de Andrade Barbosa Co-orientador: Prof. Ms. Gilberto Garcia da RochaObjetivo: Avaliar a qualidade de vida no trabalho (QVT) e nível de estresse dos trabalhadores da Atenção Primária à Saúde (APS) do distrito leste de Foz do Iguaçu-PR. Metodologia: Trata-se de estudo transversal no qual participaram 120 profissionais da APS pertencentes a 06 UBS do referido distrito. Os profissionais responderam questionários sociodemográfico, de QVT abreviado (QWLQ-Bref) e Escala do Estresse Percebido (PSS 13). Verificou-se associação da QVT e dos níveis de estresse com variáveis sociodemográficas com uso do teste t de Student, ANOVA, Mann-Whitney e Kruskal-Wallis. Nível de significância adotado foi de 5%. Resultados: A avaliação da QVT dos profissionais foi 62,8±10,0 e associou-se com sexo (p=0,016), idade (p=0,042), presença de dor (p=0,029) e satisfação com trabalho (p=0,002). Em relação aos domínios avaliados da QVT, houve associação com presença de dor e satisfação laboral. O escore total médio de estresse percebido dos participantes foi 24,5±6,0. Notou-se relação com as variáveis percepção quanto à alimentação saudável (p=0,013), presença de dor (p=0,002), dor relacionada ao trabalho (p=0,004) e satisfação com trabalho (p=0,001). Conclusão: Constatou-se satisfatória QVT e níveis médios de estresse dos profissionais o que demanda ações preventivas que melhorem esse panorama na APS do municípioObjective: To evaluate the quality of working life (QWL) and stress level of workers at Primary Health Care (PHC) in the east district of Foz do Iguaçu-PR. Methodology: Cross- sectional study with 120 PHC professionals from 06 basic health units of this district. Professionals answered sociodemographic questionnaire, abbreviated QLW (QWLQ-Bref) and Perceived Stress Scale (PSS 13). We verified the association of QWL and stress levels with sociodemographic variables using Student's t-test, ANOVA, Mann-Whitney and Kruskal-Wallis. Level of significance was 5%. Results: The professional QWL assessment was 62.8 ± 10.0 and was associated with gender (p=0.016), age (p=0.042), presence of pain (p = 0.029) and work satisfaction (p=0.002). In relation to the evaluated domains of QWL, there was an association with presence of pain and job satisfaction. The mean total perceived stress score of the participants was 24.5 ± 6.0. There was a relationship with the variables of perception regarding healthy eating (p=0.013), presence of pain (p=0.002), pain related to work (p=0.004) and satisfaction with work (p=0.001). Conclusion: We observed satisfactory QWL and mean levels of stress of PHC workers that demand improvement of this situationObjetivo: Evaluar la calidad de vida en el trabajo (QVT) y nivel de estrés de los trabajadores de la Atención Primaria a la Salud (APS) del distrito este de Foz do Iguaçu-PR. Metodología: Se trata de un estudio transversal en el que participaron 120 profesionales de la APS pertenecientes a 06 UBS de dicho distrito. Los profesionales respondieron cuestionarios sociodemográficos, de QVT abreviado (QWLQ-Bref) y Escala del estrés percibido (PSS 13). Se verificó asociación de QVT y de los niveles de estrés con variables sociodemográficas con el uso del test t de Student, ANOVA, Mann-Whitney y Kruskal-Wallis. El nivel de significancia adoptado fue del 5%. Resultados: La evaluación de la QVT de los profesionales fue de 62,8 ± 10,0 y se asoció con sexo (p=0,016), edad (p=0,042), presencia de dolor (p=0,029) y satisfacción con el trabajo (p=0,029) 0,002). En relación a los ámbitos evaluados de la QVT, hubo asociación con presencia de dolor y satisfacción laboral. La puntuación total promedio de estrés percibido de los participantes fue de 24,5 ± 6,0. Se observó relación con las variables percepción en cuanto a la alimentación sana (p=0,013), presencia de dolor (p=0,002), dolor relacionado al trabajo (p=0,004) y satisfacción con el trabajo (p=0,001). Conclusión: Se constató satisfactoria QVT y niveles medios de estrés de los profesionales lo que demanda acciones preventivas que mejoren ese panorama en la APS del municipi

Selective Over-Expression of Endothelin-1 in Endothelial Cells Exacerbates Inner Retinal Edema and Neuronal Death in Ischemic Retina

The level of endothelin-1 (ET-1), a potent vasoconstrictor, was associated with retinopathy under ischemia. The effects of endothelial endothelin-1 (ET-1) over-expression in a transgenic mouse model using Tie-1 promoter (TET-1 mice) on pathophysiological changes of retinal ischemia were investigated by intraluminal insertion of a microfilament up to middle cerebral artery (MCA) to transiently block the ophthalmic artery. Two-hour occlusion and twenty-two-hour reperfusion were performed in homozygous (Hm) TET-1 mice and their non-transgenic (NTg) littermates. Presence of pyknotic nuclei in ganglion cell layer (GCL) was investigated in paraffin sections of ipsilateral (ischemic) and contralateral (non-ischemic) retinae, followed by measurement of the thickness of inner retinal layer. Moreover, immunocytochemistry of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS) and aquaporin-4 (AQP4) peptides on retinal sections were performed to study glial cell reactivity, glutamate metabolism and water accumulation, respectively after retinal ischemia. Similar morphology was observed in the contralateral retinae of NTg and Hm TET-1 mice, whereas ipsilateral retina of NTg mice showed slight structural and cellular changes compared with the corresponding contralateral retina. Ipsilateral retinae of Hm TET-1 mice showed more significant changes when compared with ipsilateral retina of NTg mice, including more prominent cell death in GCL characterized by the presence of pyknotic nuclei, elevated GS immunoreactivity in Müller cell bodies and processes, increased AQP-4 immunoreactivity in Müller cell processes, and increased inner retinal thickness. Thus, over-expression of endothelial ET-1 in TET-1 mice may contribute to increased glutamate-induced neurotoxicity on neuronal cells and water accumulation in inner retina leading to edema

Overexpression of Na ؉ -Dependent Myo-inositol Transporter Gene in Mouse Lens Led to Congenital Cataract

PURPOSE. Maintaining appropriate osmotic pressure is essential for maintaining lens transparency. This study was performed to investigate whether high levels of myo-inositol, one of the major organic osmolytes in the lens, would lead to cataract development. METHODS. Transgenic mouse lines carrying the bovine Na ϩ -dependent myo-inositol transporter (bSMIT) cDNA under the control of the mouse ␣A-crystallin promoter were generated. RESULTS. Increased bSMIT expression was accompanied by increased myo-inositol level in the lens and increased uptake of ( 3 H) myo-inositol by the lens in culture. The transgenic mice developed observable cataract under normal rearing conditions beginning at 2 to 8 weeks of age, and the severity of cataract development was correlated to the level of bSMIT gene expression and lens myo-inositol accumulation. For transgenic mouse line 3352, heterozygous mice did not develop cataract, whereas homozygous ones did. Prenatal feeding of heterozygous 3352 mice with high myo-inositol diet led to cataract development, indicating that cataract development was not merely due to a nonspecific effect of SMIT overexpression. Introducing aldose reductase overexpressing transgene into heterozygous 3352 mice also led to cataract development, indicating that this type of cataract is primarily due to osmotic stress. CONCLUSIONS. The present results indicate that high levels of myo-inositol and sorbitol in the lens contribute to cataract development. This is a useful model to study the role of osmotic stress in cataractogenesis during lens development. (Invest Ophthalmol Vis Sci. 2000;41:1467-1472 C ataract is the most important cause of blindness in the world. Nearly 16 million people are estimated to be blind because of cataract. 1 There are a number of causes for cataract, including congenital cataract, cataract from infection, cataract from UV and X-ray irradiation and oxidation damage, and cataract associated with several diseases, particularly diabetes. The transparency in mammalian lenses is due to the presence of crystallin structures formed by highly ordered association of several proteins. Changes in ionic environment, a reduction in the level of antioxidants such as reduced glutathione and ascorbic acid, and changes in the level of other solutes may lead to random protein aggregation and disruption of the crystallin structures, resulting in lens opacity and cataract. Therefore, the lens needs to stabilize the intracellular osmotic pressure by regulating the influx and efflux of water, osmolytes, and other solutes. Osmotic stress due to the accumulation of sorbitol in the lens is most likely the cause of diabetic cataract. This is based on the fact that sorbitol accumulates to high levels in the lenses of diabetic animals 6 Development of lens opacity in vitro can be prevented by AR inhibitors or if the medium is made hypertonic to balance the increased sorbitol accumulation in the lens, indicating that osmotic stress is the cause of diabetic cataract. 9 To determine whether cataract caused by sorbitol accumulation is a consequence of osmotic stress rather than the toxic effect of sorbitol, we wanted to increase the lens myoinositol (MI) level to see if that also causes cataract. Myoinositol is one of the three major osmolytes in the lens besides sorbitol and taurine. 10 Influx of MI into lens is dependent on the Na ϩ -dependent MI transporter (SMIT). 11 In this study, we produced transgenic mice that overexpress SMIT constitutively in lens cells and found that they developed congenital cataract under normal rearing condition beginning at 2 to 8 weeks of age. These results provide strong evidence that a high level o

Inducible Nucleosome Depletion at OREBP-Binding-Sites by Hypertonic Stress

Background: Osmotic Response Element-Binding Protein (OREBP), also known as TonEBP or NFAT5, is a unique transcription factor. It is hitherto the only known mammalian transcription factor that regulates hypertonic stress-induced gene transcription. In addition, unlike other monomeric members of the NFAT family, OREBP exists as a homodimer and it is the only transcription factor known to bind naked DNA targets by complete encirclement in vitro. Nevertheless, how OREBP interacts with target DNA, also known as ORE/TonE, and how it elicits gene transcription in vivo, remains unknown. Methodology: Using hypertonic induction of the aldose reductase (AR) gene activation as a model, we showed that OREs contained dynamic nucleosomes. Hypertonic stress induced a rapid and reversible loss of nucleosome(s) around the OREs. The loss of nucleosome(s) was found to be initiated by an OREBP-independent mechanism, but was significantly potentiated in the presence of OREBP. Furthermore, hypertonic induction of AR gene was associated with an OREBPdependent hyperacetylation of histones that spanned the 59 upstream sequences and at least some exons of the gene. Nevertheless, nucleosome loss was not regulated by the acetylation status of histone. Significance: Our findings offer novel insights into the mechanism of OREBP-dependent transcriptional regulation and provide a basis for understanding how histone eviction and transcription factor recruitment are coupled. © 2009 Tong et al.published_or_final_versio

Aldose reductase regulates microglia/macrophages polarization through the cAMP response element-binding protein after spinal cord injury in mice.

Inflammatory reactions are the most critical pathological processes occurring after spinal cord injury (SCI). Activated microglia/macrophages have either detrimental or beneficial effects on neural regeneration based on their functional polarized M1/M2 subsets. However, the mechanism of microglia/macrophage polarization to M1/M2 at the injured spinal cord environment remains unknown. In this study, wild-type (WT) or aldose reductase (AR)-knockout (KO) mice were subjected to SCI by a spinal crush injury model. The expression pattern of AR, behavior tests for locomotor activity, and lesion size were assessed at between 4 h and 28 days after SCI. We found that the expression of AR is upregulated in microglia/macrophages after SCI in WT mice. In AR KO mice, SCI led to smaller injury lesion areas compared to WT. AR deficiency-induced microglia/macrophages induce the M2 rather than the M1 response and promote locomotion recovery after SCI in mice. In the in vitro experiments, microglia cell lines (N9 or BV2) were treated with the AR inhibitor (ARI) fidarestat. AR inhibition caused 4-hydroxynonenal (HNE) accumulation, which induced the phosphorylation of the cAMP response element-binding protein (CREB) to promote Arg1 expression. KG501, the specific inhibitor of phosphorylated CREB, could cancel the upregulation of Arg1 by ARI or HNE stimulation. Our results suggest that AR works as a switch which can regulate microglia by polarizing cells to either the M1 or the M2 phenotype under M1 stimulation based on its states of activity. We suggest that inhibiting AR may be a promising therapeutic method for SCI in the future

Embryonic Lethality in Mice Lacking the Nuclear Factor of Activated T Cells 5 Protein Due to Impaired Cardiac Development and Function

Nuclear factor of activated T cells 5 protein (NFAT5) is thought to be important for cellular adaptation to osmotic stress by regulating the transcription of genes responsible for the synthesis or transport of organic osmolytes. It is also thought to play a role in immune function, myogenesis and cancer invasion. To better understand the function of NFAT5, we developed NFAT5 gene knockout mice. Homozygous NFAT5 null (NFAT5−/−) mouse embryos failed to develop normally and died after 14.5 days of embryonic development (E14.5). The embryos showed peripheral edema, and abnormal heart development as indicated by thinner ventricular wall and reduced cell density at the compact and trabecular areas of myocardium. This is associated with reduced level of proliferating cell nuclear antigen and increased caspase-3 in these tissues. Cardiomyocytes from E14.5 NFAT5−/− embryos showed a significant reduction of beating rate and abnormal Ca2+ signaling profile as a consequence of reduced sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and ryanodine receptor (RyR) expressions. Expression of NFAT5 target genes, such as HSP 70 and SMIT were reduced in NFAT5−/− cardiomyocytes. Our findings demonstrated an essential role of NFAT5 in cardiac development and Ca2+ signaling. Cardiac failure is most likely responsible for the peripheral edema and death of NFAT5−/− embryos at E14.5 days

Acute Response of Peripheral Blood Cell to Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetic Patient

Autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) was the first therapeutic approach that can improve β cell function in type 1 diabetic (T1D) patients. This study was designed to investigate the potential mechanisms involved.We applied AHST to nine T1D patients diagnosed within six months and analyzed the acute responses in peripheral blood for lymphocyte subpopulation as well as for genomic expression profiling at the six-month follow-up.We found six patients obtained insulin free (IF group) and three remained insulin dependent (ID group); C-peptide production was significantly higher in IF group compared to ID group. The acute responses in lymphocytes at six-month follow-up include declined CD3(+)CD4(+), CD3(+)CD8(+) T cell population and recovered B cell, NK cell population in both groups but with no significant differences between the two groups; most immune-related genes and pathways were up-regulated in peripheral blood mononuclear cell (PBMC) of both groups while none of transcription factors for immune regulatory component were significantly changed; the IF group demonstrated more AHST-modified genetic events than the ID group and distinct pattern of top pathways, co-expression network as well as 'hub' genes (eg, TCF7 and GZMA) were associated with each group.AHST could improve the islet function in newly diagnosed T1D patients and elimination of the islet specific autoreactive T cells might be one of the mechanisms involved; T1D patients responded differently to AHST possibly due to the distinct transcriptional events occurring in PBMC.ClinicalTrials.gov NCT00807651

Deleted in Liver Cancer 2 (DLC2) Was Dispensable for Development and Its Deficiency Did Not Aggravate Hepatocarcinogenesis

DLC2 (deleted in liver cancer 2), a Rho GTPase-activating protein, was previously shown to be underexpressed in human hepatocellular carcinoma and has tumor suppressor functions in cell culture models. We generated DLC2-deficient mice to investigate the tumor suppressor role of DLC2 in hepatocarcinogenesis and the function of DLC2 in vivo. In this study, we found that, unlike homologous DLC1, which is essential for embryonic development, DLC2 was dispensable for embryonic development and DLC2-deficient mice could survive to adulthood. We also did not observe a higher incidence of liver tumor formation or diethylnitrosamine (DEN)-induced hepatocarcinogenesis in DLC2-deficient mice. However, we observed that DLC2-deficient mice were smaller and had less adipose tissue than the wild type mice. These phenotypes were not due to reduction of cell size or defect in adipogenesis, as observed in the 190B RhoGAP-deficient mouse model. Together, these results suggest that deficiency in DLC2 alone does not enhance hepatocarcinogenesis

Caveolin-1 Plays a Crucial Role in Inhibiting Neuronal Differentiation of Neural Stem/Progenitor Cells via VEGF Signaling-Dependent Pathway

In the present study, we aim to elucidate the roles of caveolin-1(Cav-1), a 22 kDa protein in plasma membrane invaginations, in modulating neuronal differentiation of neural progenitor cells (NPCs). In the hippocampal dentate gyrus, we found that Cav-1 knockout mice revealed remarkably higher levels of vascular endothelial growth factor (VEGF) and the more abundant formation of newborn neurons than wild type mice. We then studied the potential mechanisms of Cav-1 in modulating VEGF signaling and neuronal differentiation in isolated cultured NPCs under normoxic and hypoxic conditions. Hypoxic embryonic rat NPCs were exposed to 1% O2 for 24 h and then switched to 21% O2 for 1, 3, 7 and 14 days whereas normoxic NPCs were continuously cultured with 21% O2. Compared with normoxic NPCs, hypoxic NPCs had down-regulated expression of Cav-1 and up-regulated VEGF expression and p44/42MAPK phosphorylation, and enhanced neuronal differentiation. We further studied the roles of Cav-1 in inhibiting neuronal differentiation by using Cav-1 scaffolding domain peptide and Cav-1-specific small interfering RNA. In both normoxic and hypoxic NPCs, Cav-1 peptide markedly down-regulated the expressions of VEGF and flk1, decreased the phosphorylations of p44/42MAPK, Akt and Stat3, and inhibited neuronal differentiation, whereas the knockdown of Cav-1 promoted the expression of VEGF, phosphorylations of p44/42MAPK, Akt and Stat3, and stimulated neuronal differentiation. Moreover, the enhanced phosphorylations of p44/42MAPK, Akt and Stat3, and neuronal differentiation were abolished by co-treatment of VEGF inhibitor V1. These results provide strong evidence to prove that Cav-1 can inhibit neuronal differentiation via down-regulations of VEGF, p44/42MAPK, Akt and Stat3 signaling pathways, and that VEGF signaling is a crucial target of Cav-1. The hypoxia-induced down-regulation of Cav-1 contributes to enhanced neuronal differentiation in NPCs

Upregulation of UCP2 by Adiponectin: The Involvement of Mitochondrial Superoxide and hnRNP K

Background: The adipocyte-derived hormone adiponectin elicits protective functions against fatty liver diseases and hepatic injuries at least in part by stimulating the expression of a mitochondrial inner membrane transporter, uncoupling protein 2 (UCP2). The present study was designed to investigate the cellular and molecular mechanisms underlying adiponectin-induced UCP2 expression. Methodology/Principal Findnigs: Mice were treated with adiponectin and/or different drug inhibitors. Parenchymal (PCs) and nonparenchymal (NPCs) cells were fractionated from the liver tissues for mitochondria isolation, Western blotting and quantitative PCR analysis. Mitochondrial superoxide production was monitored by MitoSOX staining and flow cytometry analysis. Compared to control mice, the expression of UCP2 was significantly lower in NPCs, but not PCs of adiponectin knockout mice (AKO). Both chronic and acute treatment with adiponectin selectively increased the mRNA and protein abundance of UCP2 in NPCs, especially in the enriched endothelial cell fractions. The transcription inhibitor actinomycin D could not block adiponectin-induced UCP2 expression, whereas the protein synthesis inhibitor cycloheximide inhibited the elevation of UCP2 protein but not its mRNA levels. Mitochondrial content of heterogeneous nuclear ribonucleoprotein K (hnRNP K), a nucleic acid binding protein involved in regulating mRNA transportation and stabilization, was significantly enhanced by adiponectin, which also evoked a transient elevation of mitochondrial superoxide. Rotenone, an inhibitor of mitochondrial respiratory complex I, abolished adiponectin-induced superoxide production, hnRNP K recruitment and UCP2 expression. Conclusions/Significance: Mitochondrial superoxide production stimulated by adiponectin serves as a trigger to initiate the translocation of hnRNP K, which in turn promotes UCP2 expressions in liver. © 2012 Zhou et al.published_or_final_versio