Hiperoxia hiperbárica em infecções graves e sepse: conceitos e perspectivas

We did a review, considering the relevant factors that could play a role in using hyperbaric oxygen therapy in sepsis. Specially in intra-abdominal infecctions due to gut Gram negative bacteria, stressing upon its interest to clinical and laboratory research. Some concepts related to hypoxia and oxidative metabolism are described, reviewing the role of oxygen free radical (reactive oxygen species or ROS) and anti-oxidants in sepsis development. The clinical use of HOT and in the clinical setting, and its potential in severe infections, are discussed.Efetua-se uma revisão da forma como a hiperoxigenação hiperbárica pode interferir em alguns dos fatores do quadro séptico, em especial na sepse provocada por infecções intra-abdominais, envolvendo bactérias Gram-negativas, destacando-se o seu interesse para a pesquisa experimental e clínica. São considerados alguns conceitos de hipoxia e metabolismo oxidativo na sepse, revisando-se o papel dos radicais ativados do oxigênio e antioxidantes, nesta síndrome. Conceituam-se as bases do uso da hiperoxia hiperbárica em infecções graves e sua utilização clinica atual

The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer

© 2019 Pinto, Rios, Durães, Ribeiro, Machado, Mantovani, Barbosa, Carneiro and Oliveira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Macrophages are one of the immune populations frequently found in colorectal tumors and high macrophage infiltration has been associated with both better and worst prognosis. Importantly, according to microenvironment stimuli, macrophages may adopt different polarization profiles, specifically the pro-inflammatory or M1 and the anti-inflammatory or M2, which display distinct functions. Therefore, concomitantly with the number of tumor-associated macrophages (TAMs), their characterization is fundamental to unravel their relevance in cancer. Here, we profiled macrophages in a series of 150 colorectal cancer (CRC) cases by immunohistochemistry, using CD68 as a macrophage lineage marker, CD80 as a marker of pro-inflammatory macrophages, and CD163 as a marker of anti-inflammatory macrophages. Quantifications were performed by computer-assisted analysis in the intratumoral region, tumor invasive front, and matched tumor adjacent normal mucosa (ANM). Macrophages, specifically the CD163+ ones, were predominantly found at the tumor invasive front, whereas CD80+ macrophages were almost exclusively located in the ANM, which suggests a predominant anti-inflammatory polarization of TAMs. Stratification according to tumor stage revealed that macrophages, specifically the CD163+ ones, are more prevalent in stage II tumors, whereas CD80+ macrophages are predominant in less invasive T1 tumors. Specifically in stage III tumors, higher CD68, and lower CD80/CD163 ratio associated with decreased overall survival. Importantly, despite the low infiltration of CD80+ cells in colorectal tumors, multivariate logistic regression revealed a protective role of these cells regarding the risk for relapse. Overall, this work supports the involvement of distinct microenvironments, present at the intra-tumor, invasive front and ANM regions, on macrophage modulation, and uncovers their prognostic value, further supporting the relevance of including macrophage profiling in clinical settings.This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT/MCTES in the framework of the project MAGICIAM: a MAcrophaGe Immunomodulatory-delivery system to prevent Cancer Invasion and Metastasis (POCI-01-0145-FEDER-031859). FCT further supported this work under MP PhD grant (PD/BD/81103/2011), CD post-doctoral grant (SFRH/BPD/99442/2014), and MO FCT Investigator grant (IF/01066/2012).info:eu-repo/semantics/publishedVersio

Evaluation of extracts from Coccoloba mollis using the Salmonella/microsome system and in vivo tests

The common everyday use of medicinal plants is an ancient, and still very widespread practice, whereby the need for studies on their possible toxicity and mutagenic properties. The species Coccoloba mollis has been much used in phytotherapy, mainly in cases involving loss of memory and stress. In order to investigate its genotoxic and mutagenic potential, ethanolic extracts from the leaves and roots underwent Salmonella/microsome assaying (TA98 and TA100 strains, with and without exogenous metabolism – S9), besides comet and micronucleus tests in vivo.There was no significant increase in the number of revertants/plate of Salmonella strains in any of the analyzed root-extract concentrations, although the extract itself was extremely toxic to the Salmonella TA98 strain in the tests carried out with S9 (doses varying from 0.005 to 0.5 μg/plate). On the other hand, the leaf-extract induced mutations in the TA98 strain in the absence of S9 in the highest concentration evaluated, although at very low mutagenic potency (0.004 rev/ μg). Furthermore, there was no statistically significant increase in the number of comets and micronuclei, in treatments involving Swiss mice. It was obvious that extracts of Coccoloba mollis, under the described experimental conditions, are not mutagenic

Determination of the antimutagenicity of an aqueous extract of Rhizophora mangle L. (Rhizophoraceae), using in vivo and in vitro test systems

An aqueous extract of Rhizophora mangle L. bark is used as raw material in pottery making in the State of Espirito Santo, Brazil. This extract presents large quantities of tannins, compounds possessing antioxidant properties. Tannin antioxidant activity, as a plant chemical defense mechanism in the process of stabilizing free radicals, has been an incentive to studies on anti-mutagenicity. The present work aimed to evaluate possible antimutagenic activity of a R. mangle aqueous extract, using the Allium cepa test-system and micronuclear (MN) assay with blockage of cytokinesis in Chinese hamster ovary cells (CHO-K1). The Allium cepa test-system indicated antimutagenic activity against the damage induced by the mutagenic agent methyl methanesulfonate. A reduction in both MN cell frequency and chromosome breaks occurred in both the pre and post-treatment protocols. The MN testing of CHO-K1 cells revealed anti-mutagenic activity of the R. mangle extract against methyl methanesulfonate and doxorubicin in pre, simultaneous and post-treatment protocols. These results suggest the presence of phyto-constituents in the extract presenting demutagenic and bio-antimutagenic activities. Since the chemical constitution of Rhizophora mangle species presents elevated tannin content, it is highly probable that these compounds are the antimutagenic promoters themselves

Influência da omentoplastia na anastomose cólica de animais submetidos a choque hemorrágico em ratos

PURPOSE: To analyze influence of omentoplasty on anastomosis in descending colon of rats. Rats were submitted to the hypovolemic shock of the hemorrhagic type by the Biomechanical Test of Pressure of Rupture by Liquid Distension (BTPRLD). In addition, establish a type of acute anemia in rats that are provided to the study. METHODS: Comparative study between two groups of animals with ten rats in each one, all submitted to hemorrhagic shock for 30% volemic removal by the carotid artery. An anastomosis was performed in left colon. An anastomosis was performed in the left colon. Group 1 took place anastomosis with Polyvinyl Chloride (P.V.C) film to prevent the adhesions formation on sature line. Group 2 placed the great omentum around the anastomosis. Euthanasia occurred on the fifth day, when the anastomoses were submitted to the biomechanical test of pressure of rupture by liquid distension (BTPRLD). RESULTS: High rupture pressure was gained with omentoplasty group in relation to the group in which anastomosis was protected from adhesions formation. A statistical significance was noted. CONCLUSION: Protection by great omentum has increased the anastomosis resistance of the shocked animals. Also, the proposed hemorrhagic shock type has proven to be useful for this study.OBJETIVO: Analisar a influência da omentoplastia sobre anastomose realizada em cólon descendente de ratos que foram submetidos a choque hipovolêmico do tipo hemorrágico, por meio do Teste Biomecânico de Pressão de Ruptura à Distensão por Líquido. Além disso, estabelecer modelo de anemia aguda em rato que se preste ao referido estudo. MÉTODOS: Estudo comparativo entre dois grupos de animais com 10 ratos em cada, todos submetidos a choque hemorrágico por retirada volêmica de 30% através da artéria carótida, sendo realizada anastomose em cólon esquerdo. No grupo 1 realizou-se proteção da anastomose com película de polivinilcloreto para impedir a formação de aderências sobre a linha de sutura; no grupo 2 colocou-se em torno da anastomose o grande omento. A eutanásia deu-se no quinto dia, quando as anastomoses foram submetidas ao Teste Biomecânico Pressão de Ruptura à Distensão por Líquido (TBPRDL). RESULTADOS: Obteve-se maior pressão de ruptura no grupo em que se realizou a omentoplastia em relação ao grupo em que a anastomose foi protegida da formação de aderências, notando-se significância estatística. CONCLUSÃO: A proteção pelo grande omento aumentou a resistência das anastomoses dos animais chocados. Também, o modelo de choque hemorrágico proposto mostrou-se útil para este estudo.23323

RELAÇÃO ENTRE DEPRESSÃO E POSTURA DE MULHERES MASTECTOMIZADAS

A mastectomia é uma técnica cirúrgica necessária no tratamento do câncer de mama, porém pode causar sensações de estresse, gerando ansiedade e depressão. Esses fatores são responsáveis por desequilíbrios no organismo, como mialgias e alterações posturais. O objetivo desta pesquisa é contribuir para elucidar lacunas na literatura, como a relação entre a depressão e a postura de mulheres mastectomizadas. Participaram deste estudo 40 mulheres, de 40 a 70 anos, subdivididas em grupo experimental – GE (n=20) composto por mastectomizadas e grupo controle – GC (n=20) com mulheres sem a enfermidade. A coleta de dados baseou-se na tomada de fotografias, inserção destas imagens digitais no Software de Avaliação Postural (SAPO) e posterior análise postural. Para avaliação do estado depressivo foi utilizado o Inventário de Depressão de Beck. Os resultados não foram estatisticamente significantes, entretanto, constatou-se a existência de assimetrias corporais comuns no GE como elevação de ombro, anteriorização de cabeça, inclinação posterior de tronco e retroversão pélvica. Esse estudo conclui que a postura corporal e a depressão não estão associadas à presença da mastectomia

Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment:interim analysis from a phase II clinical trial

BACKGROUND: We developed a personalized Monocyte-Derived Dendritic-cell Therapy (MDDCT) for HIV-infected individuals on suppressive antiretroviral treatment and evaluated HIV-specific T-cell responses. METHODS: PBMCs were obtained from 10 HIV(+) individuals enrolled in trial NCT02961829. Monocytes were differentiated into DCs using IFN-α and GM-CSF. After sequencing each patient’s HIV-1 Gag and determining HLA profiles, autologous Gag peptides were selected based on the predicted individual immunogenicity and used to pulse MDDCs. Three doses of the MDDCT were administered every 15 days. To assess immunogenicity, patients’ cells were stimulated in vitro with autologous peptides, and intracellular IL-2, TNF, and interferon-gamma (IFN-γ) production were measured in CD4(+) and CD8(+) T-cells. RESULTS: The protocol of ex-vivo treatment with IFN-α and GM-CSF was able to induce maturation of MDDCs, as well as to preserve their viability for reinfusion. MDDCT administration was associated with increased expression of IL-2 in CD4(+) and CD8(+) T-cells at 15 and/or 30 days after the first MDDCT administration. Moreover, intracellular TNF and IFN-γ expression was significantly increased in CD4(+) T-cells. The number of candidates that increased in vitro the cytokine levels in CD4(+) and CD8(+) T cells upon stimulation with Gag peptides from baseline to day 15 and from baseline to day 30 and day 120 after MDDCT was significant as compared to Gag unstimulated response. This was accompanied by an increasing trend in the frequency of polyfunctional T-cells over time, which was visible when considering both cells expressing two and three out of the three cytokines examined. CONCLUSIONS: MDDC had a mature profile, and this MDDCT promoted in-vitro T-cell immune responses in HIV-infected patients undergoing long-term suppressive antiretroviral treatment. Trial registration NCT02961829: (Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure, https://www.clinicaltrials.gov/ct2/show/NCT02961829, posted November 11th, 2016) SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12981-021-00426-z

Intricate macrophage-colorectal cancer cell communication in response to radiation

Both cancer and tumour-associated host cells are exposed to ionizing radiation when a tumour is subjected to radiotherapy. Macrophages frequently constitute the most abundant tumour-associated immune population, playing a role in tumour progression and response to therapy. The present work aimed to evaluate the importance of macrophage-cancer cell communication in the cellular response to radiation. To address this question, we established monocultures and indirect co-cultures of human monocyte-derived macrophages with RKO or SW1463 colorectal cancer cells, which exhibit higher and lower radiation sensitivity, respectively. Mono- and co-cultures were then irradiated with 5 cumulative doses, in a similar fractionated scheme to that used during cancer patients' treatment (2 Gy/fraction/day). Our results demonstrated that macrophages sensitize RKO to radiation-induced apoptosis, while protecting SW1463 cells. Additionally, the co-culture with macrophages increased the mRNA expression of metabolism- and survival-related genes more in SW1463 than in RKO. The presence of macrophages also upregulated glucose transporter 1 expression in irradiated SW1463, but not in RKO cells. In addition, the influence of cancer cells on the expression of pro- and anti-inflammatory macrophage markers, upon radiation exposure, was also evaluated. In the presence of RKO or SW1463, irradiated macrophages exhibit higher levels of pro-inflammatory TNF, IL6, CCL2 and CCR7, and of anti-inflammatory CCL18. However, RKO cells induce an increase of macrophage pro-inflammatory IL1B, while SW1463 cells promote higher pro-inflammatory CXCL8 and CD80, and also anti-inflammatory VCAN and IL10 levels. Thus, our data demonstrated that macrophages and cancer cells mutually influence their response to radiation. Notably, conditioned medium from irradiated co-cultures increased non-irradiated RKO cell migration and invasion and did not impact on angiogenesis in a chicken embryo chorioallantoic membrane assay. Overall, the establishment of primary human macrophage-cancer cell co-cultures revealed an intricate cell communication in response to ionizing radiation, which should be considered when developing therapies adjuvant to radiotherapy