Protective effects of mito-TEMPO against doxorubicin cardiotoxicity in mice

Doxorubicin (DOX) is a chemotherapeutic that is widely used for the treatment of many human tumors. However, the development of cardiotoxicity has limited its use. The aim of the present study was to evaluate the possible efficacy of mito-TEMPO (mito-T) as a protective agent against DOX-induced cardiotoxicity in mice. C57BL/6 mice were treated twice with mito-T at low (5 mg/kg body weight) or high (20 mg/kg body weight) dose and once with DOX (24 mg/kg body weight) or saline (0.1 mL/20 g body weight) by means of intraperitoneal injections. The levels of malondialdehyde (MLDA), a marker of lipid peroxidation, and serum levels of creatine kinase were evaluated 48 h after the injection of DOX. DOX induced lipid peroxidation in heart mitochondria (p < 0.001), and DOX-treated mice receiving mito-T at low dose had levels of MLDA significantly lower than the mice that received only DOX (p < 0.01). Furthermore, administration of mito-T alone did not cause any significant changes from control values. Additionally, DOX-treated mice treated with mito-T at high dose showed decrease in serum levels of total CK compared to mice treated with DOX alone (p < 0.05). Our results indicate that mito-T protects mice against DOX-induced cardiotoxicity.Fundacao de Amparo a Pesquisa do Estado da Bahia-FAPESB, State Government of Bahia, BrazilFundacao Oswaldo Cruz, BrazilConselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq, Ministry of Science and Technology, BrazilFundacao Oswaldo Cruz, Goncallo Moniz Res Ctr, Rua Waldemar Falcao 121, BR-40296710 Salvador, BA, BrazilUniv Fed Sao Paulo, Lab Imunol Celular & Bioquim Fungos & Protozoario, Sao Paulo, BrazilUCL, London, EnglandUniv Fed Sao Paulo, Lab Imunol Celular & Bioquim Fungos & Protozoario, Sao Paulo, BrazilWeb of Scienc

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Oxidative stress in sepsis. Possible production of free radicals through an erythrocyte-mediated positive feedback mechanism

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-02-20T16:06:11Z No. of bitstreams: 1 Oliveira YPA Oxidative stress....pdf: 1726919 bytes, checksum: 34cbdb0d686efc7d31d3896afb45476b (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-02-20T16:15:00Z (GMT) No. of bitstreams: 1 Oliveira YPA Oxidative stress....pdf: 1726919 bytes, checksum: 34cbdb0d686efc7d31d3896afb45476b (MD5)Made available in DSpace on 2017-02-20T16:15:00Z (GMT). No. of bitstreams: 1 Oliveira YPA Oxidative stress....pdf: 1726919 bytes, checksum: 34cbdb0d686efc7d31d3896afb45476b (MD5) Previous issue date: 2017FIOCRUZ-Bahia (Centro dePesquisas Gonçalo Moniz) for allowing the experiments whichneeded to be done, FAPESB for the financial support as well asthe Institutions and individuals who agreed to take part in thisProject.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilSepsis is an illness with a high morbidity for which no effective treatment exists. Its treatment has a high cost because it usually requires an intensive care unit and expensive antibiotics. The present study focus in the production of reactive oxygen species in the early stages of sepsis. This study aimed at investigating the production of reactive oxygen specie during the inflammatory response in patients with sepsis.Methods: Reactive oxygen specie production and insoluble myeloperoxidase obtained fromfresh whole blood were measured by photon counting chemiluminescence in the blood of18 septic patients and 12 healthy individuals. Modified red blood cells were evaluated bystaining of blood smears. The production of reactive oxygen species by macrophages andpolymorphonuclear leukocytes put into contact with modified red blood cells were alsoassessed by photon counting chemiluminescence.Results: The appearance of oxidatively modified erythrocytes, which is an evidence ofoxidative stress, was supported by the detection of reactive oxygen species and insolublemyeloperoxidase in the whole blood of all septic patients. Peroxynitrite was the main reac-tive oxygen species found in the whole blood. Oxidatively modified erythrocytes activatedphagocytic cells in vitro, leading to the considerable production of free radicals.Conclusion: It was found that sepsis led to a high oxidative stress and to extensive modifi-cation of erythrocytes. It is proposed that a positive feedback mechanism, involving theactivation of circulating leukocytes by these modified erythrocytes would maintain thepro-oxidative state even after the disappearance of bacteria

Leishmania amazonensis fails to induce the release of reactive oxygen intermediates by CBA macrophages.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-05-30T11:44:46Z No. of bitstreams: 1 Almeida TF Leishmania amazonensis....pdf: 549441 bytes, checksum: be4373bbc97f2d7b75430f8b8f393253 (MD5)Made available in DSpace on 2014-05-30T11:44:46Z (GMT). No. of bitstreams: 1 Almeida TF Leishmania amazonensis....pdf: 549441 bytes, checksum: be4373bbc97f2d7b75430f8b8f393253 (MD5) Previous issue date: 2012Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilCBA mouse macrophages effectively control Leishmania major infection, yet are permissive to Leishmania amazonensis. It has been established that some Leishmania species are destroyed by reactive oxygen species (ROS). However, other species of Leishmania exhibit resistance to ROS or even down-modulate ROS production. We hypothesized that L. amazonensis-infected macrophages reduce ROS production soon after parasite-cell interaction. Employing a highly sensitive analysis technique based on chemiluminescence, the production of superoxide (O(·-)(2)) and hydrogen peroxide (H(2)O(2)) by L. major- or L. amazonensis-infected CBA macrophages were measured. L. major induces macrophages to release levels of (O(·-)(2)) 3·5 times higher than in uninfected cells. This (O(·-)(2)) production is partially dependent on NADPH oxidase (NOX) type 2. The level of accumulated H(2)O(2) is 20 times higher in L. major-than in L. amazonensis-infected cells. Furthermore, macrophages stimulated with L. amazonensis release amounts of ROS similar to uninfected cells. These findings support previous studies showing that CBA macrophages are effective in controlling L. major infection by a mechanism dependent on both (O(·-)(2)) production and H(2)O(2) generation. Furthermore, these data reinforce the notion that L. amazonensis survive inside CBA macrophages by reducing ROS production during the phagocytic process

Tuberculosis

Texto completo: acesso restrito. p. 218–225Background The existence of ectosome-like microvesicles released by neutrophils was proposed a few decades ago. Other studies revealed that the innate immune response during mycobacterial infection is accompanied by an intense migration of neutrophils to the site of infection, which may be important during the acute phase of tuberculosis. We found that the ectosomes derived from infected neutrophils are biologically active and can influence the survival of Mycobacterium tuberculosis within macrophages. Methods Mycobacteria were cultured on supplemented Middlebrook-7H9 broth. All strains were grown to the exponential phase and quantitated by serial dilution. Human neutrophils and macrophages were infected with mycobacteria. Ectosomes from neutrophils were isolated post-infection and characterized by transmission electron microscopy and flow cytometry. To determine whether these microvesicles influenced mycobactericidal activity, mycobacteria-infected macrophages were treated with isolated ectosomes. Results Ectosomes were released from neutrophils infected with mycobacteria. These ectosomes were derived from neutrophil plasma membrane and a small proportion stained with PKH26. These microvesicles, when incubated with infected macrophages, influenced antimycobacterial activity. Conclusions This is the first study to demonstrate that ectosomes that are shed from infected neutrophils influence mycobactericidal activity in macrophages in vitro, suggesting that these microvesicles have biological significance. Nevertheless, major gaps in our knowledge of microvesicle biology remain

Mycobacterium tuberculosis-induced neutrophil ectosomes decrease macrophage activation.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-11-12T14:04:23Z No. of bitstreams: 1 Duarte TA Mycobacterium....pdf: 1042368 bytes, checksum: 72a82354af873a14f7ec429585669248 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2014-11-12T14:04:32Z (GMT) No. of bitstreams: 1 Duarte TA Mycobacterium....pdf: 1042368 bytes, checksum: 72a82354af873a14f7ec429585669248 (MD5)Made available in DSpace on 2014-11-12T14:22:42Z (GMT). No. of bitstreams: 1 Duarte TA Mycobacterium....pdf: 1042368 bytes, checksum: 72a82354af873a14f7ec429585669248 (MD5) Previous issue date: 2012Federal University of Bahia. Health Science Institute. Salvador, BA, Brasil / Federal University of Rio de Janeiro. Clementino Fraga Filho University Hospital, Department of Internal Medicine. Multidisciplinary Research Laboratory. Rio de Janeiro, RJ, BrasilUniversity College London. Gower Street, London, UK / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFederal University of Rio de Janeiro. Clementino Fraga Filho University Hospital, Department of Internal Medicine. Multidisciplinary Research Laboratory. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFederal University of Rio de Janeiro. Clementino Fraga Filho University Hospital, Department of Internal Medicine. Multidisciplinary Research Laboratory. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFederal University of Rio de Janeiro. Clementino Fraga Filho University Hospital, Department of Internal Medicine. Multidisciplinary Research Laboratory. Rio de Janeiro, RJ, BrasilBACKGROUND: The existence of ectosome-like microvesicles released by neutrophils was proposed a few decades ago. Other studies revealed that the innate immune response during mycobacterial infection is accompanied by an intense migration of neutrophils to the site of infection, which may be important during the acute phase of tuberculosis. We found that the ectosomes derived from infected neutrophils are biologically active and can influence the survival of Mycobacterium tuberculosis within macrophages. METHODS: Mycobacteria were cultured on supplemented Middlebrook-7H9 broth. All strains were grown to the exponential phase and quantitated by serial dilution. Human neutrophils and macrophages were infected with mycobacteria. Ectosomes from neutrophils were isolated post-infection and characterized by transmission electron microscopy and flow cytometry. To determine whether these microvesicles influenced mycobactericidal activity, mycobacteria-infected macrophages were treated with isolated ectosomes. RESULTS: Ectosomes were released from neutrophils infected with mycobacteria. These ectosomes were derived from neutrophil plasma membrane and a small proportion stained with PKH26. These microvesicles, when incubated with infected macrophages, influenced antimycobacterial activity. CONCLUSIONS: This is the first study to demonstrate that ectosomes that are shed from infected neutrophils influence mycobactericidal activity in macrophages in vitro, suggesting that these microvesicles have biological significance. Nevertheless, major gaps in our knowledge of microvesicle biology remain

Journal of Leukocyte Biology

Texto completo: acesso restrito. p. 389-396Neutrophils are involved in the initial steps of most responses to pathogens. In the present study, we evaluated the effects of the interaction of apoptotic vs. necrotic human neutrophils on macrophage infection by Leishmania amazonensis. Phagocytosis of apoptotic, but not viable, neutrophils by Leishmania-infected macrophages led to an increase in parasite burden via a mechanism dependent on TGF-β1 and PGE2. Conversely, infected macrophages’ uptake of necrotic neutrophils induced killing of L. amazonensis. Leishmanicidal activity was dependent on TNF-α and neutrophilic elastase. Nitric oxide was not involved in the killing of parasites, but the interaction of necrotic neutrophils with infected macrophages resulted in high superoxide production, a process reversed by catalase, an inhibitor of reactive oxygen intermediate production. Initial events after Leishmania infection involve interactions with neutrophils; we demonstrate that phagocytosis of these cells in an apoptotic or necrotic stage can influence the outcome of infection, driving either parasite survival or destruction