Aerobic physical training reduces severe asthma phenotype involving kinins pathway.

INTRODUCTION: Aerobic physical training (APT) reduces eosinophilic airway inflammation, but its effects and mechanisms in severe asthma remain unknown. METHODS: An in vitro study employing key cells involved in the pathogenesis of severe asthma, such as freshly isolated human eosinophils, neutrophils, and bronchial epithelial cell lineage (BEAS-2B) and lung fibroblasts (MRC-5 cells), was conducted. Additionally, an in vivo study using male C57Bl/6 mice, including Control (Co; n = 10), Trained (Exe; n = 10), house dust mite (HDM; n = 10), and HDM + Trained (HDM + Exe; n = 10) groups, was carried out, with APT performed at moderate intensity, 5x/week, for 4 weeks. RESULTS: HDM and bradykinin, either alone or in combination, induced hyperactivation in human neutrophils, eosinophils, BEAS-2B, and MRC-5 cells. In contrast, IL-10, the primary anti-inflammatory molecule released during APT, inhibited these inflammatory effects, as evidenced by the suppression of numerous cytokines and reduced mRNA expression of the B1 receptor and ACE-2. The in vivo study demonstrated that APT decreased bronchoalveolar lavage levels of bradykinin, IL-1ß, IL-4, IL-5, IL-17, IL-33, TNF-α, and IL-13, while increasing levels of IL-10, klotho, and IL-1RA. APT reduced the accumulation of polymorphonuclear cells, lymphocytes, and macrophages in the peribronchial space, as well as collagen fiber accumulation, epithelial thickness, and mucus accumulation. Furthermore, APT lowered the expression of the B1 receptor and ACE-2 in lung tissue and reduced bradykinin levels in the lung tissue homogenate compared to the HDM group. It also improved airway resistance, tissue resistance, and tissue damping. On a systemic level, APT reduced total leukocytes, eosinophils, neutrophils, basophils, lymphocytes, and monocytes in the blood, as well as plasma levels of IL-1ß, IL-4, IL-5, IL-17, TNF-α, and IL-33, while elevating the levels of IL-10 and IL-1RA. CONCLUSION: These findings indicate that APT inhibits the severe asthma phenotype by targeting kinin signaling.

Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling.

OBJECTIVE: To evaluate the chemical composition and effects of Artemisia vulgaris (AV) hydroalcoholic extract (HEAV) on breast cancer cells (MCF-7 and SKBR-3), chronic myeloid leukemia (K562) and NIH/3T3 fibroblasts. METHODS: Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass (HPLC) spectrometry. Viability and cell death studies were performed using trypan blue and Annexin/FITC-7AAD, respectively. Ferrostatin-1 (Fer-1) and necrostatin-1 (Nec-1) were used to assess the mode of HEAV-induced cell death and acetoxymethylester (BAPTA-AM) was used to verify the involvement of cytosolic calcium in this event. Cytosolic calcium measurements were made using Fura-2-AM. RESULTS: HEAV decreased the viability of MCF-7, SKBR-3 and K562 cells (P<0.05). The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts (P<0.05). Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD (P<0.05). The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone (P<0.01). HEAV-induced Ca2+ release mainly from lysosomes in K562 cells (P<0.01). Furthermore, BAPTA-AM, an intracellular Ca2+ chelator, decreased the number of non-viable cells treated with HEAV (P<0.05). CONCLUSIONS: HEAV is cytotoxic and activates several modalities of cell death, which are partially dependent on lysosomal release of Ca2+. These effects may be related to artemisinin and caffeoylquinic acids, the main compounds identified in HEAV.

A phytotherapic blend immunity-6™ inhibits myeloid leukemic cells 2 activation involving purinergic signaling.

Leukemia is among the most common types of hematological cancers and the use of herbal medicines to prevent and treat leukemia are under quick development. Among several molecular pathways involved in leukemia pathogenesis and exacerbations, purinergic signaling is revealed as a key component. In the present study, the effects of two doses (5 ug/mL and 10 ug/mL) of Immunity-6™, a phytocomplex composed by beta-glucan, green tea (Camelia sinensis), chamomile (Matricaria chamomilla), and ascorbic acid (vitamin C) was tested in vitro, using chronic myelogenous leukemia cell line (K-562; 5 ×104/mL/well), which were challenged with lipopolysaccharide (LPS; 1 ug/mL) for 24 h. The results demonstrated that both doses of Immunity-6™ inhibited ATP release (p < 0.001) and P2×7 receptor at mRNA levels expression (p < 0.001). Purinergic inhibition by Immunity-6™ was followed by reduced release of proinflammatory cytokines IL-1beta (p < 0.001) and IL-6 (p < 0.001), while only 5 ug/mL of Immunity-6™ reduced the release of TNF-alpha (p < 0.001). Beyond to inhibit the release of pro-inflammatory cytokines, both doses of Immunity-6™ induced the release of anti-inflammatory cytokine IL-10 (p < 0.001), while only the higher dose (10 ug/mL) of Immunity-6™ induced the release of anti-inflammatory IL-1ra (p < 0.05) and klotho (p < 0.001). Thus, Immunity-6™ may be a promising adjuvant in the treatment of leukemia and further clinical trials are guaranteed.

A Nutritional Blend Suppresses the Inflammatory Response from Bronchial Epithelial Cells Induced by SARS-CoV-2.

Even after virus elimination, numerous sequelae of coronavirus disease 2019 (COVID-19) persist. Based on accumulating evidence, large amounts of proinflammatory cytokines are released to drive COVID-19 progression, severity, and mortality, and their levels remain elevated after the acute phase of COVID-19, playing a central role in the disease' sequelae. In this manner, bronchial epithelial cells are the first cells hyperactivated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to massive cytokine release, triggering the hyperactivation of leukocytes and other cells, and mediating COVID-19 sequelae. Therefore, proinflammatory cytokine production is initiated by the host. This in vitro study tested the hypothesis that ImmuneRecov™, a nutritional blend, inhibits the SARS-CoV-2-induced hyperactivation of human bronchial epithelial cells (BEAS-2B). BEAS-2B (5x104/mL/well) cells were cocultivated with 1 ml of blood from a SARS-CoV-2-infected patient for 4 h, and the nutritional blend (1 µg/mL) was added in the first minute of coculture. After 4 h, the cells were recovered and used for analyses of cytotoxicity with the (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay and the expression of the IL-1ß, IL-6, and IL-10 mRNAs. The supernatant was collected to measure cytokine levels. SARS-CoV-2 incubation resulted in increased levels of IL-1ß and IL-6 in BEAS-2B cells (p < 0.001). Treatment with the nutritional blend resulted in reduced levels of the proinflammatory cytokines IL-1ß and IL-6 (p < 0.001) and increased levels of the anti-inflammatory cytokine IL-10 (p < 0.001). Additionally, the nutritional blend reduced the expression of the IL-1ß and IL-6 mRNAs in SARS-CoV-2-stimulated cells and increased the expression of the IL-10 and IFN-γ mRNAs. In conclusion, the nutritional blend exerts important anti-inflammatory effects on cells in the context of SARS-CoV-2 infection.

Hydrolyzed Collagen Induces an Anti-Inflammatory Response That Induces Proliferation of Skin Fibroblast and Keratinocytes.

Collagen-based products are found in different pharmaceuticals, medicine, food, and cosmetics products for a wide variety of applications. However, its use to prevent or improve the health of skin is growing dizzyingly. Therefore, this study investigated whether collagen peptides could induce fibroblast and keratinocyte proliferation and activation beyond reducing an inflammatory response induced by lipopolysaccharide (LPS). Human skin fibroblasts (CCD-1072Sk) and human keratinocytes (hKT-nh-skp-KT0026) were seeded at a concentration of 5 × 104 cells/mL. LPS (10 ng/mL) and three doses of collagen peptides (2.5 mg/mL, 5 mg/mL, 10 mg/mL) were used. The readout parameters were cell proliferation; expression of inducible nitric oxide synthase (iNOS); expression of pro-collagen-1α by fibroblasts; and secretion of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), transforming growth factor ß (TGF-ß), and vascular endothelial growth factor (VEGF) by both cell types. The results demonstrated that all doses of collagen supplementation induced increased proliferation of both human fibroblasts (p < 0.01) and human keratinocytes (p < 0.001), while only the dose of 10 mg/mL induced an increased expression of pro-collagen-1α by fibroblasts. Similarly, only the dose of 10 mg/mL reduced LPS-induced iNOS expression in fibroblasts (p < 0.05) and keratinocytes (p < 0.01). In addition, collagen supplementation reduced the LPS-induced IL-1ß (p < 0.05), IL-6 (p < 0.001), IL-8 (p < 0.01), and TNF-α (p < 0.05), and increased the TGF-ß and VEGF expression in fibroblasts. Furthermore, collagen supplementation reduced the LPS-induced IL-1ß (p < 0.01), IL-6 (p < 0.01), IL-8 (p < 0.01), and TNF-α (p < 0.001), and increased the TGF-ß (p < 0.05) and VEGF (p < 0.05) expression in keratinocytes. In conclusion, collagen peptides were found to induce fibroblast and keratinocyte proliferation and pro-collagen-1α expression, involving increased expression of TGF-ß and VEGF, as well as the suppression of an inflammatory response induced by LPS.

Molecular Dereplication and In Vitro and In Silico Pharmacological Evaluation of Coriandrum sativum against Neuroblastoma Cells.

The aim of this study was to investigate the cytotoxic activity of the Coriandrum sativum (C. sativum) ethanolic extract (CSEE) in neuroblastoma cells, chemically characterize the compounds present in the CSEE, and predict the molecular interactions and properties of ADME. Thus, after obtaining the CSEE and performing its chemical characterization through dereplication methods using UPLC/DAD-ESI/HRMS/MS, PM6 methods and the SwissADME drug design platform were used in order to predict molecular interactions and ADME properties. The CSEE was tested for 24 h in neuroblastoma cells to the establishment of the IC50 dose. Then, the cell death was evaluated, using annexin-PI, as well as the activity of the effector caspase 3, and the protein and mRNA levels of Bax and Bcl-2 were analyzed by ELISA and RT-PCR, respectively. By UHPLC/DAD/HRMS-MS/MS analysis, the CSEE showed a high content of isocoumarins-dihydrocoriandrin, coriandrin, and coriandrones A and B, as well as nitrogenated compounds (adenine, adenosine, and tryptophan). Flavonoids (apigenin, hyperoside, and rutin), phospholipids (PAF C-16 and LysoPC (16:0)), and acylglicerol were also identified in lower amount as important compounds with antioxidant activity. The in silico approach results showed that the compounds 1 to 6, which are found mostly in the C. sativum extract, obey the "Five Rules" of Lipinski, suggesting a good pharmacokinetic activity of these compounds when administered orally. The IC50 dose of CSEE (20 µg/mL) inhibited cell proliferation and promoted cell death by the accumulation of cleaved caspase-3 and the externalization of phosphatidylserine. Furthermore, CSEE decreased Bcl-2 and increased Bax, both protein and mRNA levels, suggesting an apoptotic mechanism. CSEE presents cytotoxic effects, promoting cell death. In addition to the promising results predicted through the in silico approach for all compounds, the compound 6 showed the best results in relation to stability due to its GAP value.

Antiviral activity of medicinal plant-derived products against SARS-CoV-2.

This review presents information from several studies that have demonstrated the antiviral activity of extracts (Andrographis paniculata, Artemisia annua, Artemisia afra, Cannabis sativa, Curcuma longa, Echinacea purpurea, Olea europaea, Piper nigrum, and Punica granatum) and phytocompounds derived from medicinal plants (artemisinins, glycyrrhizin, and phenolic compounds) against SARS-CoV-2. A brief background of the plant products studied, the methodology used to evaluate the antiviral activity, the main findings from the research, and the possible mechanisms of action are presented. These plant products have been shown to impede the adsorption of SARS-CoV-2 to the host cell, and prevent multiplication of the virus post its entry into the host cell. In addition to antiviral activity, the plant products have also been demonstrated to exert an immunomodulatory effect by controlling the excessive release of cytokines, which is commonly associated with SARS-CoV-2 infections.

MiodesinTM Positively Modulates the Immune Response in Endometrial and Vaginal Cells.

Endometriosis presents high prevalence and its physiopathology involves hyperactivation of endometrial and vaginal cells, especially by bacteria. The disease has no cure and therapies aiming to inhibit its development are highly desirable. Therefore, this study investigated whether MiodesinTM (10 µg/mL = IC80; 200 µg/mL = IC50), a natural compound constituted by Uncaria tomentosa, Endopleura uchi, and astaxanthin, could exert anti-inflammatory and anti-proliferative effects against Lipopolysaccharides (LPS) stimulation in endometrial and Candida albicans vaginal cell lines. VK2 E6/E7 (vaginal) and KLE (epithelial) cell lines were stimulated with Candida albicans (1 × 107 to 5 × 107/mL) and LPS (1 µg/mL), respectively. MiodesinTM inhibited mRNA expression for Nuclear factor kappa B (NF-κB), ciclo-oxigenase 1 (COX-1), and phospholipase A2 (PLA2), beyond the C-C motif chemokine ligand 2 (CCL2), CCL3, and CCL5 in VK2 E6/E7 cells (p < 0.05). In addition, the inhibitory effects of both doses of MiodesinTM (10 µg/mL and 200 µg/mL) resulted in reduced secretion of interleukin-1ß (IL-1ß), IL-6, IL-8, tumor necrosis factor α (TNF-α) (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 (p < 0.05) by VK2 E6/E7 cells. In the same way, COX-1 MiodesinTM inhibited LPS-induced hyperactivation of KLE cells, as demonstrated by reduced secretion of IL-1ß, IL-6, IL-8, TNF-α (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 (p < 0.05). Furthermore, MiodesinTM also inhibited mRNA expression and secretion of matrix metalloproteinase-2 (MMP-2), MMP-9, and vascular endothelial growth factor (VEGF), which are key regulators of invasion of endometrial cells. Thus, the study concludes that MiodesinTM presents beneficial effects in the context of endometriosis, positively affecting the inflammatory and proliferative response.

Therapeutic use of intravenous selenium in respiratory and immunological diseases: evidence based on reviews focused on clinical trials.

The oxidative stress caused by systemic inflammatory response syndrome (SIRS), septic shock, and sepsis, is a risk factor triggering an increase in mortality in patients diagnosed with these pathologies. Selenium (Se) is an essential mineral that has antioxidant and cytoprotective functions, being strongly associated with the proper functioning of intracellular metabolic processes. In this context, the present study aims to investigate de therapeutic effects of intravenous selenium use considering pathologies such as SIRS, septic shock, sepsis, acute respiratory distress syndrome (ARDS), ventilator associated pneumonia (VAP), and coronavirus disease (COVID-19). This is an narrative literature review in which six main articles found in databases of SciELO, PubMed, and Google Scholar, were selected and analyzed. As a result, articles were found evidencing the benefit of Se in the inflammatory response, increasing the GPx-3 activity and decreasing the inflammatory cytokines, in addition to generating a lower risk of VAP, shortening the hospitalization time, and mortality. Thus, Se supplementation has beneficial evidence for acute respiratory diseases and should be considered as a viable option as adjuvant therapy.

Transfer factors peptides (Imuno TF®) modulate the lung inflammation and airway remodeling in allergic asthma.

Background: Allergic asthma is a chronic lung disease in which the lung inflammation and airway remodeling are orchestrated by both the inflammatory and the immune cells that creates a lung millieu that favors the perpetuation of clinical symptoms. The cell signaling in asthma involves the mast cells activation during initial contact with the allergen and, principally, the participation of eosinophils as well as Th2 cells which determine increased levels of IgE, exaggerated secretion of mucus and collagen, and bronchial hyperreactivity. Moreover, allergic asthma presents lower level of cytokines associated to the both Th1 and Treg cells response, and it implies in deficiency of anti-inflammatory response to counterregulate the exaggerated inflammation against allergen. Therefore, the equilibrium between cytokines as well as transcription factors associated to Th2, Th1, and Treg cells is compromised in allergic asthma. Imuno TF® is a food supplement with ability to interfere in immune system pathways. It has been previously demonstrated that Imuno TF® upregulated Th1 cell response whilst downregulated Th2 cell response in human lymphocytes. Objective: For this reason, we hypothesized that the Imuno TF effect could be restore the balance between Th1/Th2 CD4 T cells response in murine allergic asthma. Methods: Initially, animals were sensitized with OVA via i.p. and challenged with OVA i.n. on days 14, 15 and 16. Treatment with Imuno TF once a day was performed via orogastric from day 17 to day 20. Mice were euthanized on day 21. Results: The Imuno TF reduced eosinophilia, mucus production, and airway remodeling (collagen deposition) in asthma mice. Imuno TF influenced cellular signaling associated to allergic asthma once downregulated STAT6 expression as well as decreased IL-4, IL-5, and IL-13 in lung and serum. In addition, Imuno TF restored T-bet and Foxp3 expression as well as increased IL-12, IFN-É£, and IL-10. Conclusion: Ultimately, Imuno TF mitigated the allergic asthma due to the restoration of balance between the responses of Th1/Th2 as well as Treg cells, and their respective transcription factors the T-bet/STAT6 and Foxp3.

Evaluation of cytokine profile in the different phases of the autologous hematopoietic stem cell transplantation in patients with multiple myeloma.

BACKGROUND: The autologous hematopoietic stem cell transplantation (ASCT) is of fundamental importance in the treatment of patients with multiple myeloma (MM). Nevertheless, due to its toxicity, it decreases the number of bone marrow cells available, altering the cell interactions and causing an imbalance between pro- and anti-inflammatory cytokines. METHODS: Thus, we determined the serum levels of pro- and anti-inflammatory cytokines in samples of patients with MM obtained from the different phases of ASCT. RESULTS: In summary, the cytokines levels varied considering the different phases of ASCT. The levels of IL-1ra tend to increase in the post-apheresis period suggesting an anti-inflammatory role induced by the apheresis process. A response characterized by the increase in the concentrations of IL-5 and IL-8 was observed in the post-conditioning bone marrow aplasia phase. The rise in IL-5 levels was not correlated with any clinical or laboratory event in this framework; IL-8 was associated with positive blood cultures and seems to have an effect against microbial agents. The increase in the levels of IL-10 and IL-12 suggests a possible regulatory effect of the inflammatory response in the period of bone marrow recovery and IL-12 seems to be inversely associated with the presence of minimal residual disease. CONCLUSIONS: Apheresis process seems to induce an anti-inflammatory response, followed by a pro-inflammatory response and a stimulus for granulocytes differentiation.

Anti-Inflammatory Activity of Miodesin™: Modulation of Inflammatory Markers and Epigenetic Evidence.

PURPOSE: To investigate the effects of a combined herbal medicine Miodesin™ on the inflammatory response of key cells involved in the acute and chronic inflammatory processes as well as the possible epigenetic involvement. METHODS: After the establishment of the IC50 dose, the chondrocyte, keratinocyte, and macrophage cell lines were pretreated for 2 hours with Miodesin™ (200 µg/mL) and stimulated with LPS (1 µg/mL) for 24 hours. The supernatant was used to measure the levels of cytokines (IL-1ß, IL-6, IL-8, and TNF-α) and chemokines (CCL2, CCL3, and CCL5), and the cells were used to extract the mRNA for the transcription factor (NF-κß), inflammatory enzymes (COX-1, COX-2, PLA2, and iNOS), and chemokines (CCL2, CCL3, and CCL5). RESULTS: Miodesin™ inhibited the release of LPS-induced cytokines (IL-1ß, IL-6, IL-8, and TNF-α; p < 0.01) and chemokines (CCL2, CCL3, and CCL5; p < 0.01) and the expression of the transcription factor (NF-κß; p < 0.01), inflammatory enzymes (COX-1, COX-2, PLA2, iNOS; p < 0.01), and chemokines (CCL2, CCL3, and CCL5; p < 0.01). In addition, the evaluation of epigenetic mechanism revealed that Miodesin™ did not induce changes in DNA methylation, assuring the genetic safeness of the compound in terms of the inflammatory response. CONCLUSIONS: Miodesin™ presents anti-inflammatory properties, inhibiting hyperactivation of chondrocytes, keratinocytes, and macrophages, involving epigenetics in such effects.

First-year students' perceptions of team-based learning in a new medical genetics course / Percepção dos alunos do primeiro ano sobre a aprendizagem baseada em equipes em um novo curso de genética médica

ABSTRACT Background Medical education has evolved considerably over the last few years, especially through adoption of new technologies and active methodologies. These methodologies aim to improve learning and engage students deeply in the process. TBL is a methodology widely used in health schools, including Medical Schools. We can use it to work with large groups, divided into small teams. The students first work individually, then within teams, and finally the groups cooperate to solve applied problems. Objectives To describe students' perceptions and satisfaction about a Medical Genetics course organized into blocks of subject in which we used TBL sessions with first-year medical students. Methods A Medical Genetics course were organized into subject blocks in which a TBL session was conducted in each of these blocks to improve the learning process. At the end of the course, the students answered a questionnaire on satisfaction and perceptions. Results By the first time we described a Medical Genetics course organized into 5 blocks of subject matter on a total of 25 genetic diseases in which a TBL session was conducted in each of these blocks. We enrolled a total of 290 participants and 96% of the students were satisfied with TBL. Furthermore, 97% of students believe that TBL helped them to learn, and 87% approved of use of TBL in the future at other stages of their medical course. Conclusion Application of the TBL method during a medical genetics course was well-received by students and proved an important tool in the structures of curricula for medical education at this university.

RESUMO Introdução A educação médica evoluiu consideravelmente nos últimos anos, especialmente através da adoção de novas tecnologias e metodologias ativas. Essas metodologias visam melhorar a aprendizagem e envolver os alunos profundamente no processo. O TBL é uma metodologia amplamente utilizada em escolas de saúde, incluindo escolas médicas. Podemos usá-lo para trabalhar com grandes grupos, divididos em pequenas equipes. Primeiro, os alunos trabalham individualmente, depois dentro das equipes e, finalmente, os grupos cooperam para resolver os problemas aplicados. Objetivos Descrever as percepções e a satisfação dos alunos em relação a um curso de Genética Médica organizado em blocos de assuntos em que utilizamos sessões de TBL com estudantes de medicina do primeiro ano. Métodos Um curso de Genética Médica foi organizado em blocos de assuntos em que uma sessão de TBL foi realizada em cada um desses blocos para melhorar o processo de aprendizagem. No final do curso, os alunos responderam a um questionário sobre satisfação e percepções. Resultados Pela primeira vez nós descrevemos um curso de Genética Médica organizado em 5 blocos de assuntos, compreendendo 25 doenças genéticas, nos quais, uma sessão de TBL foi conduzida em cada um desses blocos. Participaram um total de 290 alunos, dos quais 96% estavam satisfeitos com o método de TBL. Além disso, 97% dos estudantes acreditam que o TBL os ajudou a aprender, e 87% aprovaram o uso do TBL no futuro, em outras etapas de seu curso de medicina. Conclusão A aplicação do método TBL durante um curso de genética médica foi bem recebida pelos estudantes e se mostrou uma ferramenta importante na estruturação curricular para a educação médica nesta universidade.

In vitro cytotoxicity of chemical preservatives on human fibroblast cells

Preservatives are widely used substances that are commonly added to various cosmetic and pharmaceutical products to prevent or inhibit microbial growth. In this study, we compared the in vitro cytotoxicity of different types of currently used preservatives, including methylparaben, imidazolidinyl urea (IMU), and sodium benzoate, using the human newborn fibroblast cell line CCD1072Sk. Of the tested preservatives, only IMU induced a reduction in cell viability, as shown using the MTT assay and propidium iodide staining (IMU>methylparaben>sodium benzoate). IMU was shown to promote homeostatic alterations potentially related to the initiation of programed cell death, such as decreased mitochondrial membrane potential and caspase-3 activation, in the treated cells. Methylparaben and sodium benzoate were shown to have a very low cytotoxic activity. Taken together, our results suggest that IMU induces programed cell death in human fibroblasts by a canonical intrinsic pathway via mitochondrial perturbation and subsequent release of proapoptotic factors

Avaliação in vitro da atividade do ácido hialurônico de baixo peso molecular sobre a proliferação de fibroblástos dérmicos humanos / In vitro evaluation of acid activity hyaluronic acid of low molecular weight on proliferation of human dermal fibroblasts

O ácido hialurônico de baixo peso molecular (AH) é proposto como agente que atua nas três fases da reparação tecidual. O objetivo deste trabalho foi avaliar se o AH é capaz de induzir proliferação celular de fibroblastos dérmicos humanos. Esses efeitos foram avaliados empregando-se as técnicas de azul de tripano e de brometo de [3-(4,5-dimetiltiazol-2yl)-2,5-difenil tetrazolium] (MTT),seguida de análise do ciclo celular, produção de colágeno e modelo de wound healing (WH). Após tratamento com AH, foi verificado aumento significativo na proliferação das células e nas fases S-G2-M do ciclo celular. Quando submetido ao teste de WH, a exposição a 0,2% de AH promoveu redução significativa da área da lesão, com taxas de migração celular de 74%. Os resultados confirmam a capacidade do AH em aumentar a proliferação de fibroblastos, o que é relevante para a fase proliferativa da cicatrização.

In vitro study activity proliferative fibroblast human submitted to treatment zincum metallicum and calendula officinalis in ultra dilutions homeopathic

Cicatrization can be divided into three phases: inflammation, fibroblastic, maturation and remodeling [1]. The extracellular matrix may be replaced by a stronger and more elastic connective tissue. In a scar collagen is the major component of the mature connective tissue [2]. In homeopathic area, the greater is the investigated segment ultra dilutions [6]. However, little research has been done to explore the effect of dynamized drugs in in vitro cell culture [4]. Using the Zincum metallicum 6CH and Calendula officinalis 6CH applied independently in different concentrations in fibroblast cultures sought to determine the increase in proliferative activity using techniques such as IC50, MTT, flow cytometry and quantification of collagen. As expected from the literature, ie both homeopathic according to the literature are used for treatments that Require skin healing, both showed increased proliferative activity, having Calendula most cellular response, presenting as cell cycle stimulating checked via flow cytometry.(AU)

In vitro study activity proliferative fibroblast human submitted to treatment Zincummetallicum and Calendula officianlis in homeopathic ultra dilutions

Cicatrization can be divided into three phases: inflammation, fibroblastic, maturation and remodeling [1]. The extracellular matrix may be replaced by a stronger and more elastic connective tissue. In a scar collagen is the major component of the mature connective tissue [2]. In homeopathic area, the greater is the investigated segment ultra dilutions [6]. However, little research has been done to explore the effect of dynamized drugs in in vitro cell culture [4]. Using the Zincum metallicum 6CH and Calendula officinalis 6CH applied independently in different concentrations in fibroblast cultures sought to determine the increase in proliferative activity using techniques such as IC50, MTT, flow cytometry and quantification of collagen. As expected from the literature, ie both homeopathic according to the literature are used for treatments that Require skin healing, both showed increased proliferative activity, having Calendula most cellular response, presenting as cell cycle stimulating checked via flow cytometry.

Plantas com potencial adaptogénico utilizadas na medicina popular brasileira: Ptychapetalum olacaides, Pfaffia spp. E Trichilia catigua / Plantas con potencial adaptogénico utilizadas en la medicina popular brasileña: Ptychopetalum olacoides, Pfaflia spp. y Trichilia catigua / Potentially adaptogenic plants used in Brazilian folk medicine: Ptychopetalum olacoides, Pfaffia spp. A Trichilia catigua

O estresse já foi definido como uma reaçáo capaz de perturbar a homeostase do organismo. Nesse contexto es adaptógenos permitem equilibrar o organismo durante tais situaçoes. Pesquisas demonstram que a flora brasileira e rica em especies com potencial adaptógeno, dentre as quais destacam: Ptycopetalum olacoides (marapuama), descrita por seus efeitos anti-inflamatórios, antioxidante, antibacteriano e estimulante de sistema imunológico; o genero Pfaffia spp, entre eles o ginseng brasileiro, com usos na fadiga cronica, estresse, impotencia masculina e reduçáo nos niveis circulantes de colesterol; e a Trichilia catigua (catuaba) utilizada como tonico para tratamento do estresse, fadiga, impotencia e déficit de memoria (AU)

El estrés se define como una reacción capaz de alterar la homeostasis del organismo. En este contexto, los adaptógenes permiten equilibrar el organismo en tales situaciones. Las investigaciones han mostrado que la fiera brasileña es rica en especies con potencial adaptegénice, entre las que destacan: Ptycopetalum olacoides (marapuama), descrita por sus efectos estimulantes, antiinflamatories, antioxidantes, antibacterianes e inmuneestimulantes; Pfaffia spp, (ginseng brasileño), con usos en fatiga crónica, estrés, impotencia masculina y reducción de los niveles plasmáticos de colesterol; y Trichilia catigua (catuaba), utilizada en el tratamiento del estrés, la fatiga, la impotencia y el déficit de memoria (AU)

Stress has already been defined as a reaction able to disrupt the homeostasis of the organism. In this context adaptogens allow te balance the body in such situations. Research has shown that Brazilian flora is rich in species with adaptegenic potential, among which the following are outstanding: Ptycopetalum olacoides (marapuama), known for its anti-inflammatory, antiexidant, antibacterial and immunestimulant effects; the genus Pfaffia spp, including the Brasilian ginseng, used in chronic fatigue, stress, male impotence and reduction of blood cholesterol levels; and Trichilia catigua (catuaba) used for the treatment of stress, fatigue, impotence and memory deficit (AU)

Hemoculturas: estudo da prevalência dos microrganismos e o perfil de sensibilidade dos antibióticos utilizados em Unidade de Terapia Intensiva / Blood cultures: study of prevalence of microorganisms profile and sensitivity of antibiotics used in Intensive Care Unit

Objetivo - O trabalho apresentado tem como objetivo o estudo sobre a prevalência de hemoculturas positivas provenientes de pacientes hospitalizados em Unidade de Terapia Intensiva (UTI), e determinar os principais microrganismos presentes nessas amostras, bem como, analisar o perfil de sensibilidade dos principais antibióticos. Métodos - Durante o período de janeiro a julho de 2011, foram analisados os resultados de 512 coletas de hemoculturas, dentre elas 308 (60,2%) eram do sexo masculino e 204 (39,8%) do sexo feminino. Resultados - A positividade foi de 24%. Numa análise geral, Staphylococcus epidermidis foi o microrganismo de maior prevalência (45,5%), seguido por Staphylococcus aureus (13,0%) e Pseudomonas aeruginosa (12,2%). A resistência a antibiótico foi maior para oxacilina (80,1%). Conclusões - O estudo mostrou que Staphylococcus sp resistentes a oxacilina é uma das principais causa de bacteremia em UTI.

Objective - The work presented has goals to study about the prevalence of blood cultures from patients hospitalized in the Intensive Care Unit (ICU), and determine the main microorganisms present in these samples, as analyze the sensitivity of the main antibiotics. Methods - During the period from January to July 2011 were analyzed the results of 512 tests from blood cultures, among them 308 (60.2%) were male and 204 (39.8%) females. Results - The positivity was 24%. In a general analysis, Staphylococcus epidermidis was the microorganism most prevalent (45.5%), followed by Staphylococcus aureus (13.0%) and Pseudomonas aeruginosa (12.2%). The antibiotic resistance to oxacillin was higher(80.1%). Conclusions - The study showed that Staphylococcus sp is a main causes of bacteremia in ICU.

Liofilização como alternativa para conservação do leite humano / Lyophilization as an alternative for conservation of breast milk

Objetivo - Os benefícios do aleitamento materno são bem descritos na literatura. Melhorar as condições de fornecimento acessível deste importante alimento a todos os lactentes é um desafio para o profissional nutricionista. Métodos - Amostras de leite humano procedentes do Banco de Leite da cidade de Taubaté, São Paulo, foram submetidas à liofilização, sendo congeladas em nitrogênio líquido a -210ºC e permanecendo no liofilizador por 24 horas. Após a liofilização as amostras foram analisadas e comparadas ao leite in natura quanto a alguns nutrientes: lipídeos por extração direta em extrator Soxhlet, glicídios redutores em lactose por titulação, proteínas por metodologia semimicro de Kjeldahl, cálcio por titulação e imunoglobulinas por eletroforese em gel de agarose com o objetivo de visualizar as bandas gama. Também foram realizadas provas de reconstituição diluindo 30g de cada amostra em 100mL de água filtrada. As análises foram realizadas em triplicata e em seguida analisadas estatisticamente. Resultados - As triplicatas analisadas apresentaram os teores de lipídeos, lactose, proteína e cálcio inalterados em comparação aos valores do leite não-liofilizado descrito na literatura. Quanto à restituição, a cor e a fluidez se mostraram semelhante ao leite in natura e a diluição foi plena. A eletroforese também demonstrou a presença da banda gama o que sugere a conservação de imunoglobulina. Conclusão - A técnica de liofilização mostrou-se muito favorável em relação a outras técnicas de conservação, já que a mesma não utiliza o aquecimento como fator determinante para diminuir a atividade de água e sim o estado físico da matéria: sublimação.

Objective - The benefits of breastfeeding have being reported in the literature. The improvement of the accessibility conditions to this important food to all infants is a challenge for the professional nutritionist. Methods - Samples of human breast milk were collected from Taubaté city, São Paulo. They were submitted to lyophilization and frozen in liquid nitrogen at -210 ºC and they were remained in lyophilizer during 24 hours. After the lyophilization, the milk was analyzed and compared with in natura milk with respect to the following nutrients: lipids by direct extraction in Soxhlet apparatus, reducing carbohydrates by titration in lactose, protein by semi-micro Kjeldahl methodology, calcium by titration and immunoglobulins by agarose gel electrophoresis in order to visualize the gamma bands. Tests of reconstitution were also carried out by diluting 30 g of dried milk in 100 mL of filtered water. The analyses were performed in triplicate and then analyzed statistically. Results - The triplicates analyzed presented levels of lipids, lactose, protein and calcium unchanged in comparison with the values of non-lyophilisate samples as described in the literature. In the restitution tests, the color and the fluidity were similar to in natura milk and the dilution was total. The electrophoresis also showed the presence of the gamma bands, that suggests the conservation of the immunoglobulin. Conclusion - The results showed that lyophilization process is favorable, compared with other conservation processes, since that is not based in the heating as the main factor to reduce the water activity, but the physical state of matter: sublimation.