Technological strategies for the use of plant-derived compounds in the preservation of fish products.

New approaches to reducing synthetic preservatives in the preservation of foods draw the attention of plant-derived bioactive compounds, especially for application in foods highly susceptible to spoilage, such as fish products. The review presents relevant data from procurement, application, and methodological research trends to investigate the potential effects of plant-derived bioactive compounds on shelf life extension in fish products. The systematization of data allowed observation that the different methods of extraction and application of bioactive plant compounds result in different effects, such as the reduction of lipid oxidation, antimicrobial effects, and maintenance of sensory characteristics, benefiting the extension of shelf life. In general, plant-derived bioactive compounds are an alternative for the preservation of fish products; however, approaches to the composition of the compounds can contribute to the optimization and efficiency of the process from a technical point of view and industrial viability.

Mesenchymal Stromal Cell Secretome for Therapeutic Application in Skin Wound Healing: A Systematic Review of Preclinical Studies.

Non-healing skin wounds remain a challenge in the healthcare system. In this sense, it is suggested that the secretome of mesenchymal stromal cells (MSCs) can be effective as a therapeutic strategy for regenerative medicine. Therefore, this systematic review aimed to determine the effects of treatment with a secretome derived from MSCs on the healing of skin wounds in a preclinical model of rodents (mice and rats). Studies were systematically retrieved from 6 databases and gray literature that provided 1,172 records, of which 25 met the inclusion criteria for qualitative analysis. Results revealed substantial heterogeneity among studies concerning experimental designs and methodologies, resulting in a high risk of bias. Together, the selected studies reported that treatment improved wound healing by (1) accelerating wound closure and improving skin repair quality; (2) reducing inflammation by decreasing the number of cells and inflammatory cytokines, accompanied by polarization of the M2 macrophage; (3) complete re-epithelialization and epidermal reorganization; (4) neovascularization promoted by proliferation of endothelial cells (CD34+) and increased levels of pro-angiogenic mediators; (5) better scar quality promoted by increased expression of collagen types I and III, as well as improved deposition and remodeling of collagen fibers. In conclusion, despite the need for alignment of methodological protocols and transparent reports in future studies, results show that the secretome of MSCs from different tissue sources corresponds to a promising tool of regenerative medicine for the treatment of skin wounds.

Early detection of lipid oxidation in infant milk formula by measuring free oxylipins-Comparison with hydroperoxide value and thiobarbituric acid reactive substance methods.

Infant milk formula was used as a model food to compare the sensitivity of thiobarbituric acid reactive substances (TBARS) and hydroperoxide methods to UPLC-MS/MS oxylipin analysis for detecting early lipid oxidation. Two different infant milk formulas were tested during 21 days of storage at 4°C. Formulas 1 and 2 contained canola oil and canola oil + 1% docosahexaenoic acid ethyl ester, respectively. Formulas were sampled up to 21 days of storage. Formula 2 had higher peroxide values than Formula 1 across all time points. However, no significant differences over time in TBARS and peroxide values in either formula were observed. Several oxylipins increased in both formulas starting on day 7 (linoleic acid and alpha-linolenic acid-derived oxylipins in Formula 1 and DHA-derived oxylipins in Formula 2). These results indicate that free oxylipins are effective in detecting early lipid oxidation and distinguishing between formulations containing different fatty acids. PRACTICAL APPLICATION: We have recently shown that primary oxidation products known as oxylipins can be measured in their free form by ultra-high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to detect early lipid oxidation. However, a head-to-head comparison of the sensitivity of this approach to conventional spectrophotometric methods has not been evaluated. Our results indicate that free oxylipin measurements are better than conventional methods in detecting early lipid oxidation in milk infant formula  distinguishing between different formulations.

Relação do senso de coerência materno com a condição socioeconômica e a cárie dentária em crianças pré-escolares no município de Manaus, Amazonas / Relationship between the maternal sense of coherence with socioeconomic status and dental caries in preschool children in the city of Manaus, Amazonas, Brazil

Objetivo:Avaliar a relação do SOC com índice Ceo-d e o SOC com as condições socioeconômicas familiares com a cárie dentária em pré-escolares (3-5 anos) do município de Manaus, capital do Estado do Amazonas. Métodos: O estudo contou com uma amostra de 89 pais e 89 crianças. Para avaliação da cárie dentária foi utilizado o índice ceo-d; o índice significativo de cárie (SiC Index) foi utilizado para avaliar a desigualdade de cárie na amostra do estudo; para avaliar o SOC materno foi utilizado o questionário (versão curta); e para avaliar as condições socioeconômicas foram utilizadas as questões do Levantamento Nacional SB Brasil 2010. Resultados: Houve uma média do ceo-d de 1,50 com maior ocorrência de cárie dentária nos participantes do gênero masculino, assim como índice SiC que se apresentou maior no gênero masculino em média 4,38. A média do senso de coerência materno foi maior entre as crianças de 5 anos de idade com um valor de 39,33 em média e no que tange às condições socioeconômicas, observaram-se que a maior parte dos participantes, 42,33 em média vive com uma renda familiar de R$1.501 a R$2.500 reais, e uma amostra considerável de 35,40 em média sobrevive com uma renda familiar de R$ 250 reais. Conclusão: Não houve uma correlação significativa entre as condições socioeconômicas e o SOC materno com o índice ceo-d.

Aim: To evaluate the relationship between SOC with the Ceo-d index and SOC with family socioeconomic conditions with dental caries in preschoolers (3-5 years) in the municipality of Manaus, capital of the State of Amazonas, Brazil. Methods: This study included a sample of 89 parents and 89 children. To evaluate dental caries, the ceo-d index was used; the significant caries index (SiC Index) was used to evaluate the inequality of caries in the study sample; to evaluate the maternal SOC, the questionnaire (short version) was applied; and to evaluate the socioeconomic conditions, the SB Brazil 2010: National Research on Oral Health was used. Results: An average ceo-d of 1.50 was found, with a higher occurrence of dental caries in male participants, as well as an SiC index that proved to be higher in males, on average by 4.38 fold. The average sense of maternal coherence was higher among 5-year-old children, with a value of 39.33 on average. As regards socioeconomic conditions, it was observed that most participants, 42.33 on average, live with a monthly family income of R$1,501 to R$2,500 reais, and a considerable sample of 35.40 on average survives on a monthly family income of R$250 reais. Conclusion: No significant correlation was found between socioeconomic conditions and maternal SOC with the ceo-d index.

Method optimization of oxylipin hydrolysis in nonprocessed bovine milk indicates that the majority of oxylipins are esterified.

The oxidation of polyunsaturated fatty acids produces bioactive primary oxidation products known as oxylipins. In many biological matrices, the majority of oxylipins are bound (i.e. esterified), and a relatively small proportion (<10%) exists in the free form. The present study tested whether this extends to bovine milk following method evaluation of various extraction and base hydrolysis protocols for measuring bound oxylipins. Free (unbound) oxylipins were also measured. Folch extraction followed by sodium carbonate hydrolysis in the presence of methanol containing 0.1% of acetic acid and 0.1% of butylated hydroxytoluene resulted in greater oxylipin concentrations and better surrogate standard recoveries compared to other methods that did not involve Folch extraction or the addition of methanol with hydrolysis base. Sodium hydroxide was better than sodium carbonate in hydrolyzing bound oxylipins under the same conditions. Milk analysis of oxylipins with mass-spectrometry following Folch extraction and sodium hydroxide hydrolysis revealed that 95% of oxylipins in bovine milk were esterified. Most of the detected oxylipins were derived from linoleic acid, which accounted for 92 and 88% of oxylipins in the free and esterified pools, respectively. These results demonstrate that the majority of bovine milk oxylipins are bound, and that linoleic-acid derived metabolites are the most abundant oxylipin species in free and bound lipid pools. Additional studies are needed to understand the role of different oxylipin pools in both calf and human nutrition. PRACTICAL APPLICATION: A method involving Folch lipid extraction and sodium hydroxide hydrolysis was validated for esterified oxylipin measurements in bovine milk. Application of the method revealed that the majority (∼95%) of oxylipins in bovine milk were bound. Linoleic-acid derived oxylipins were the most abundant species in both bound and free milk fractions (88-92%). The results highlight the presence of a new pool of oxidized lipids in milk, potentially involved in modifying its sensory and nutritional properties.

Administration of mesenchymal stem cells from adipose tissue at the hip joint of dogs with osteoarthritis: A systematic review.

This systematic review aimed to determine the effects of intra-articular administration of mesenchymal stem cells from adipose tissue in dogs with hip joint osteoarthritis (OA). Clinical trials were systematically reviewed, using PubMed, EMBASE, Cochrane Library, LILACS, Web of Science, Scopus, Open Grey, Google Scholar, and ProQuest Dissertation and Thesis without publication year restrictions. References were screened and selected based on predefined eligibility criteria by two independent reviewers, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Clinical outcomes were assessed quantitatively using clinical pain scores, physical examination, imaging examination, questionnaire responses, pain in manipulation, gait analysis, range of joint motion, and adverse effects. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Out of 1483 articles, six met the inclusion criteria for qualitative analysis, with two randomized controlled trials and four before-and-after studies. All studies reported significantly better clinical outcomes in the adipose tissue stem cells (ADSC) group with improvements in pain and function and decreased evidence of hip OA. The risk of bias was categorized as high in the before-and-after studies and moderate to high in the randomized studies. The studies were considered heterogeneous owing to clinical results and methodology. Because of this heterogeneity, it was not possible to perform meta-analysis. Assessments of ADSC reports yielded positive clinical effects that showed improvements in pain and function and decreased evidence of hip osteoarthritis. More high-level, larger-cohort dog studies that utilize standardized protocols are needed.

FGF2 Stimulates the Growth and Improves the Melanocytic Commitment of Trunk Neural Crest Cells.

Neural crest cells (NCCs) comprise a population of multipotent progenitors and stem cells at the origin of the peripheral nervous system (PNS) and melanocytes of skin, which are profoundly influenced by microenvironmental factors, among which is basic fibroblast growth factor 2 (FGF2). In this work, we further investigated the role of this growth factor in quail trunk NC morphogenesis and demonstrated its huge effect in NCC growth mainly by stimulating cell proliferation but also reducing cell death, despite that NCC migration from the neural tube explant was not affected. Moreover, following FGF2 treatment, reduced expression of the early NC markers Sox10 and FoxD3 and improved proliferation of HNK1-positive NCC were observed. Since these markers are involved in the regulation of glial and melanocytic fate of NC, the effect of FGF2 on NCC differentiation was investigated. Therefore, in the presence of FGF2, increased proportions of NCCs positives to the melanoblast marker Mitf as well as NCCs double stained to Mitf and BrdU were recorded. In addition, treatment with FGF2, followed by differentiation medium, resulted in increased expression of melanin and improved proportion of melanin-pigmented melanocytes without alteration in the glial marker Schwann myelin protein (SMP). Taken together, these data further reveal the important role of FGF2 in NCC proliferation, survival, and differentiation, particularly in melanocyte development. This is the first demonstration of FGF2 effects in melanocyte commitment of NC and in the proliferation of Mitf-positive melanoblasts. Elucidating the differentiation process of embryonic NCCs brings us a step closer to understanding the development of the PNS and then undertaking the search for advanced technologies to prevent, or treat, injuries caused by NC-related disorders, also known as neurocristopathies.

Multivariate analysis of the composition of bioactive in tea of the species Camellia sinensis.

This study deals with the development of a separation and quantification method by high performance liquid chromatography with a diode array detector (HPLC- DAD), for the determination of phenolic acids and methylxanthines in tea (Camellia Sinensis) samples. Six phenolic acids (Gallic, trans-cinnamic, caffeic, ferulic and p-coumaric acids) and two methylxanthines (caffeine, theobromine) were studied, according to the principles of green chemistry, with the goal of comparing teas with different processing level. After development and validation of separation and extraction methods was applied to 11 extracts obtained by infusions of green and black tea samples in commercial areas of the city of Salvador-BA, showing feasible and efficient. Was employed multivariate data analysis and the Tukey test to correlate the chromatographic profile with the different samples. Principal component and analysis and hierarchical cluster analysis were used for the chromatographic analysis, allowing the visualization of two groups, formed by green and black tea samples.

O impacto da disfunção sexual na qualidade de vida feminina: um estudo observacional / The impact of sexual dysfunction on the quality of life of women: an observational study

INTRODUÇÃO: A saúde sexual envolve diversos componentes em relação à sexualidade, como biológico, cultural, psicológico e social. Quando alguns desses fatores são atingidos, pode-se originar um quadro de disfunção sexual. OBJETIVO: investigar a qualidade de vida em mulheres com disfunção sexual. MATERIAIS E MÉTODOS: Estudo observacional comparativo, de corte transversal, realizado em mulheres de 18 a 59 anos do CAAP da EBMSP. Excluídas: mulheres com histórico de doença psiquiátrica grave, portadoras de doenças crônico-degenerativas neurológicas, com dispareunia de causas orgânicas, em tratamento fisioterapêutico e gestantes. Foi utilizado a FSFI ≥ 26 para o grupo com disfunção e < 26 para o grupo comparação. Instrumentos de avaliação aplicados: FSFI e 36-Item Short-Form Health Survey (SF-36). A comparação das medianas dos domínios do SF-36 e FSFI entre os grupos foi realizada pelo teste Mann-Whitney (teste não paramétrico), e das variáveis categóricas com a disfunção sexual foi feita a partir do teste qui-quadrado. RESULTADOS: Amostra 36 paciente,18 em cada grupo. As variáveis sociodemográficas e clínicas que apresentaram diferença estatística foram renda (0,001) e escolaridade (0,011). No FSFI, todos os domínios apresentaram significância (0,00). No SF-36, ao comparar os dois grupos, 06 domínios apresentaram significância estatística. CONCLUSÃO: Os resultados mostram que mulheres com disfunção sexual apresentam um impacto negativo em alguns dos aspectos da qualidade de vida. Importante salientar que, a escolaridade e a renda familiar não foram homogêneas entre os grupos, sendo assim, diante da característica do estudo, não é possível aferir relação causa e consequência na disfunção sexual com a qualidade vida das participantes. [AU]

INTRODUCTION: Sexual health involves several components in relation to sexuality, such as biological, cultural, psychological and social. When some of these factors are reached, a picture of sexual dysfunction may result. OBJECTIVE: To investigate quality of life in women with sexual dysfunction. MATERIALS AND METHODS: A cross-sectional, observational, observational study of 18- to 59-year-old women from the EBMSP CAAP. Excluded: women with a history of severe psychiatric illness, carriers of neurological chronic degenerative diseases, with dyspareunia of organic causes, in physiotherapeutic treatment and pregnant women. FSFI ≥ 26 was used for the group with dysfunction and <26 for the comparison group. Assessment instruments applied: FSFI and 36-Item Short-Form Health Survey (SF-36). The comparison of the medians of the SF-36 and FSFI domains between the groups was performed by the Mann-Whitney test (non-parametric test), and the categorical variables with the sexual dysfunction were done using the chi-square test. RESULTS: Sample 36 patient, 18 in each group. The sociodemographic and clinical variables that presented statistical difference were income (0.001) and schooling (0.011). In the FSFI, all domains presented significance (0.00). In the SF-36, when comparing the two groups, 06 domains presented statistical significance. CONCLUSION: The results show that women with sexual dysfunction have a negative impact on some aspects of quality of life. It is important to emphasize that schooling and family income were not homogeneous between the groups, so, due to the characteristics of the study, it is not possible to measure cause and consequence relationship in sexual dysfunction with quality of life of the participants. [AU]

Dos bastidores do atendimento aos desafios da informação: a importância do auxiliar administrativo no serviço de saúde

Existem muitas fazes pelas quais passam os processos de ascendência à saúde dos pacientes dentro de um hospital. O processo de atendimento dos usuários dos serviços de atendimento à saúde se iniciam desde a chegada do paciente ao hospital. Existem processos que vão além do que compreendemos como atendimento a saúde. Todos os profissionais de uma instituição hospitalar trabalham em conjunto, como uma grande equipe, onde o trabalho de um complementa o trabalho do outro e todos têm sua parcela de contribuição no atendimento dos pacientes. E todos os setores colaboram para o funcionamento da instituição. Esse trabalho salienta a parcela de contribuição dos profissionais auxiliares administrativos dentro dos serviços de saúde.

PRNP/prion protein regulates the secretion of exosomes modulating CAV1/caveolin-1-suppressed autophagy.

Prion protein modulates many cellular functions including the secretion of trophic factors by astrocytes. Some of these factors are found in exosomes, which are formed within multivesicular bodies (MVBs) and secreted into the extracellular space to modulate cell-cell communication. The mechanisms underlying exosome biogenesis were not completely deciphered. Here, we demonstrate that primary cultures of astrocytes and fibroblasts from prnp-null mice secreted lower levels of exosomes than wild-type cells. Furthermore, prnp-null astrocytes exhibited reduced MVB formation and increased autophagosome formation. The reconstitution of PRNP expression at the cell membrane restored exosome secretion in PRNP-deficient astrocytes, whereas macroautophagy/autophagy inhibition via BECN1 depletion reestablished exosome release in these cells. Moreover, the PRNP octapeptide repeat domain was necessary to promote exosome secretion and to impair the formation of the CAV1-dependent ATG12-ATG5 cytoplasmic complex that drives autophagosome formation. Accordingly, higher levels of CAV1 were found in lipid raft domains instead of in the cytoplasm in prnp-null cells. Collectively, these findings demonstrate that PRNP supports CAV1-suppressed autophagy to protect MVBs from sequestration into phagophores, thus facilitating exosome secretion.

Prion protein binding to HOP modulates the migration and invasion of colorectal cancer cells.

Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies. The generation of conventional treatments has improved, but approximately 50 % of patients with CRC who undergo potentially curative surgery ultimately relapse and die, usually as a consequence of metastatic disease. Our previous findings showed that engagement of the cellular prion protein (PrP(C)) to its ligand HSP70/90 heat shock organizing protein (HOP) induces proliferation of glioblastomas. In addition, PrP(C) has been described as an important modulator of colorectal tumor growth. Here, we investigated the biological relevance of the PrP(C)-HOP interaction in CRC cells. We demonstrate that HOP induced the migration and invasion of CRC cell lines in a PrP(C)-dependent manner and that phosphorylation of the ERK1/2 pathway is a downstream mediator of these effects. Additionally, we show that a HOP peptide with the ability to bind PrP(C) and abolish the PrP(C)-HOP interaction inhibited the migration and invasion of CRC cells. Together, these data indicate that the disruption of the PrP(C)-HOP complex could be a potential therapeutic target for modulating the migratory and invasive cellular properties that lead to metastatic CRC.

Interações proteína príon e seus ligantes STI1 e laminina: possíveis implicações na doença de Alzheimer / Interactions of the prion protein and its ligands STI1 and laminin: possible implications for Alzheimer’s disease

A Doença de Alzheimer (DA) é uma demência progressiva que tem como principais características a disfunção sináptica e a neurodegeneração em áreas específicas do cérebro, que levam a um quadro grave de perda de memória e outras habilidades cognitivas. Uma das principais características neuropatológicas é a deposiçãode placas amiloides extracelulares, que contêm principalmente o peptídeo beta-amiloide (Aβ), que é formado por um processamento alterado da proteína precursora amiloide (APP). Os oligômeros formados por Aβ (AβO) são considerados os elementos tóxicos mais importantes deste processo, esses se ligam às sinapses e estão estreitamente relacionados com a patogênese da DA. Recentemente, foi descrito que a proteína príon celular (PrPC) é um receptor para AβO, porém, os mecanismos envolvidos nesta interação e de que forma esta pode estar relacionada à DA ainda não foram elucidados. PrPC é uma glicoproteína ancorada à membrana plasmática que interage com diversos ligantes, como a proteína de matriz extracelular laminina e a co-chaperona STI1 (Stress Inducible Protein 1). Estas interações induzem neuroproteção, neuritogênese e modulam a formação de memória. Deste modo, torna-se interessante verificar um possível efeito neuroprotetor dos ligantes de PrPC contra a toxicidade produzida pelos AβO. Utilizando culturas neuronais, observamos que os tratamentos com AβO levam uma diminuição nos níveis da proteína sináptica sinaptofisina (Syp), devido a um aumento da degradação..

Alzheimer's disease (AD) is a progressive dementia mainly characterized by synaptic dysfunction and neurodegeneration in specific areas of the brain, leading to severe memory loss, and others cognitive inabilities. One of the main neuropathological characteristics is the formation of extracellular amyloid plaques, which mainly contain beta-amyloid peptide (Aβ). This peptide is formed by an alteration in the processing of the amyloid precursor protein (APP). The Aβ oligomers (AβO) are considered the major toxic components within this process where they bind to synapses and are closely related to the pathogenesis of the AD. Recently, it was reported that PrPC is a receptor for AβO, however, the mechanisms involved in this interaction and how this may be related to AD have not yet been elucidated. The cellular prion protein (PrPC) is a glycoprotein anchored to the plasma membrane that interacts with several ligands such as the co-chaperone STI1 (Stress inducible protein 1) and the extracellular matrix protein laminin. These interactions induce neuroprotection, neuritogenesis, and modulate memory formation. Therefore, it becomes interesting to verify a possible neuroprotective effect of PrPC ligands against the toxicity induced by AβO. We observed that the treatment of neuronal cultures with AβO lead to a decrease in the levels of synaptic protein synaptophysin (Syp) due to an increase of Syp degradation by the proteasome...

Systemic chemotherapy interferes in homocysteine metabolism in breast cancer patients.

BACKGROUND: Hyperhomocysteinemia in breast cancer (BC) patients can be a risk factor for thromboembolic events. This study aimed to evaluate homocysteine and its cofators (folic acid and vitamin B12) concentrations and platelet count at diagnosis of BC, 3 and 6 months after the beginning of chemotherapy treatment and to correlate them with clinical data. METHODS: Thirty-five BC patients were included; blood samples were obtained by venipuncture. Plasmatic Hcy and cofactors concentrations were measured by competitive chemiluminescent enzyme immunoassay method. Platelet count was done using an automated analyzer. Statistical analysis was performed using the software SPSS. RESULTS: During chemotherapy, homocysteine (P = 0.032) and vitamin B12 (P < 0.001) concentrations increased, while folate and platelets decreased (P < 0.001). Among the clinical data, the menopausal status showed significant positive correlation (P = 0.022) with homocysteine concentration increase. CONCLUSIONS: Evaluation of homocysteine concentrations during chemotherapy is extremely important because their levels increase during chemotherapy treatment, thus increasing the risk of thromboembolism development.

The prion protein ligand, stress-inducible phosphoprotein 1, regulates amyloid-ß oligomer toxicity.

In Alzheimer's disease (AD), soluble amyloid-ß oligomers (AßOs) trigger neurotoxic signaling, at least partially, via the cellular prion protein (PrP(C)). However, it is unknown whether other ligands of PrP(C) can regulate this potentially toxic interaction. Stress-inducible phosphoprotein 1 (STI1), an Hsp90 cochaperone secreted by astrocytes, binds to PrP(C) in the vicinity of the AßO binding site to protect neurons against toxic stimuli. Here, we investigated a potential role of STI1 in AßO toxicity. We confirmed the specific binding of AßOs and STI1 to the PrP and showed that STI1 efficiently inhibited AßO binding to PrP in vitro (IC50 of ∼70 nm) and also decreased AßO binding to cultured mouse primary hippocampal neurons. Treatment with STI1 prevented AßO-induced synaptic loss and neuronal death in mouse cultured neurons and long-term potentiation inhibition in mouse hippocampal slices. Interestingly, STI1-haploinsufficient neurons were more sensitive to AßO-induced cell death and could be rescued by treatment with recombinant STI1. Noteworthy, both AßO binding to PrP(C) and PrP(C)-dependent AßO toxicity were inhibited by TPR2A, the PrP(C)-interacting domain of STI1. Additionally, PrP(C)-STI1 engagement activated α7 nicotinic acetylcholine receptors, which participated in neuroprotection against AßO-induced toxicity. We found an age-dependent upregulation of cortical STI1 in the APPswe/PS1dE9 mouse model of AD and in the brains of AD-affected individuals, suggesting a compensatory response. Our findings reveal a previously unrecognized role of the PrP(C) ligand STI1 in protecting neurons in AD and suggest a novel pathway that may help to offset AßO-induced toxicity.

Circulating tumor cell detection during chemotherapy in patients with breast cancer is not associated with plasma homocysteine levels.

Breast cancer remains the second most frequent type of cancer in the world and the first among women, and systemic chemotherapy is an adjuvant therapeutic modality that improves survival in a great part of patients. Women with breast cancer, however, frequently show a higher risk of thromboembolism, an event associated to hyperhomocysteinemia and the presence of circulating tumor cells (CTC). Our aim is to correlate the presence of CTCs, detected by the analysis of CK19 and c-erbB2 gene expressions, and the homocysteine plasma levels in the peripheral blood in patients with breast cancer undergoing chemotherapy. Epithelial marker expression (CK19 and c-erbB2) and homocysteine levels were analyzed in a mononuclear fraction of the peripheral blood and plasma, respectively, obtained from 35 patients diagnosed with breast cancer at diagnosis and throughout chemotherapy treatment. No significant relation between the CK19 and c-erbB2 expressions and hyperhomocysteinemia was observed at any moment of the evaluation throughout the chemotherapy treatment (3 and 6 months after the onset). Among clinical data, only menopausal status showed a statistically significant correlation with homocysteine concentration. Although differences in the expressions of the analyzed epithelial markers were detected at 3 and 6 months of chemotherapy treatment, no relation between plasma homocysteine variations and the CK19 and c-erbB2 gene expressions was found in patients under chemotherapy treatment at any moment of the evaluation, suggesting that chemotherapy affects the expressions of the studied genes independently.

Epidermal growth factor (EGF) promotes the in vitro differentiation of neural crest cells to neurons and melanocytes.

Proliferation of neural crest (NC) stem cells and their subsequent differentiation into different neural cell types are key early events in the development of the peripheral nervous system. Soluble growth factors present at the sites where NC cells migrate are critical to the development of NC derivatives in each part of the body. In the present study, we further investigate the effect of microenvironmental factors on quail trunk NC development. We show for the first time that EGF induces differentiation of NC to the neuronal and melanocytic phenotypes, while fibroblast growth factor 2 (FGF2) promotes NC differentiation to Schwann cells. In the presence of both EGF and FGF2, the neuronal differentiation predominates. Our results suggest that FGF2 stimulates gliogenesis, while EGF promotes melanogenesis and neurogenesis. The combination of both growth factors stimulates neurogenesis. These findings suggest that these two growth factors may play an important role in the fate decision of NC progenitors and in the development of the peripheral nervous system.

Influência da noradrenalina na mortalidade dos idosos com choque séptico / Norepinephrine influence on mortality in elderly with septic shock

Fundamentos: Permanece controverso o uso da noradrenalina(NA) no tratamento do choque séptico(CS) em idosos, pela possível vasoconstrição excessiva e consequentemente hipoperfusão tissular. Objetivo: Analisar se o emprego da NA se associa à maior mortalidade na unidade de terapia intensiva(UTI), em idosos com CS. Métodos: Coorte prospectiva de 67 pacientes com CS e idade maior que 65 anos, monitorados com cateteres na artéria pulmonar e em vaso periférico, por período de 32 meses. Todos os pacientes utilizaram suporte ventilatório, cobertura empírica com antibióticos de largo espectro e ressuscitação volêmica. Se a pressão arterial média permanecesse menor que 70 mmhg, iniciava-se 5 ug/kg/min de dopamina(até 20 ug/kg/min), substituída por 0,1 ug/kg/min de NA(até 5 ug/kg/min) e dobutamina, na falência cardíaca. Avaliou-se: o escore APACHE II, falências orgânicas(critérios de Le Gall), troponina I, tempo de permanência na UTI, sítio primário da infecção, uso de dopamina, NA e dobutamina. Na análise estatística foram utilizados os testes t de Student, o qui-quadrado, e análise de sobrevida de Kaplan-Meier, com significância de 5 por cento. Resultados: A média da idade foi de 80 anos, sendo 51 por cento do sexo feminino. A média dos escores do APACHE II foi de 19 e do tempo de permanência de 18 dias. Ocorreram 39 óbitos. A sepse pulmonar foi prevalente(70 por cento). As falências pulmonar e cardíaca ocorreram em 69 por cento e 46 por cento dos casos, respectivamente. A troponina I foi positiva em 33 por cento. Todos fizeram uso de dopamina seguida de NA(dobutamina + NA em 12 por cento). O APACHE II (p igual 0,001), o número de falências orgânicas(p igual 0,006), a dose maior que 0,5 ug/kg/min de NA(p igual 0,001), a positividade da troponina I(p igual 0,006), o tempo de uso de dopamina(p igual 0,004) e o tempo de permanência na UTI(p igual 0,001) mostraram associação com a mortalidade. O emprego de aminas, o sítio de infecção e a idade não se correlacionaram com o óbito. Não houve correlação com a presença de falência cardíaca. Conclusão: O uso de NA em doses menores ou iguais a 0,5 ug/kg/min não se associou com a mortalidade, porém a mortalidade se correlacionou com a presença de duas ou mais falências orgânicas nos idosos, com choque séptico