Composição de um complexo de cobre (II) e ligante -[bis(piridin-2-ilmetil)amino]-3-cloropropan-2-ol e uso da mesma

DepositadaA presente invenção refere-se a uma composição de um complexo de cobre (II) e ligante -[bis (piridin-2-ilmetil)amino]-3-cloropropan-2-ol (HPCINOL) compreendendo a associação com um outro fármaco antitumoral, preferencialmente, Cisplatina, para tratamento de neoplasias de tumores sólidos ou leucemias. O efeito sinérgico demonstrado por tal composição torna a mesma uma alternativa nova e eficiente de terapia antitumoral para diferentes tipos de câncer

Evaluation of ultrastructural changes and cell death on Leishmania amazonensis promastigote forms induced by a new coordinated complex Co (II) / Avaliação de alterações ultraestruturais e morte celular em formas promastigotas de Leishmania amazonensis induzidas por um novo complexo coordenação Co (II)

Leishmaniasis are diseases caused by protozoa of the genus Leishmania and transmitted by vectors of the phlebotomine subfamily. In Brazil, the species Leishmania amazonensis is the etiological agent of the diffuse cutaneous form. Currently, the treatment employed is associated with several side effects, which stimulated the development of new alternatives for the treatment of this important neglected disease. Thus, metallocomplexes appear as a new alternative for antiparasitic therapy. Its action has been evaluated on different species of parasites of the Trypanosomatidae family, including species of the genus Leishmania. In this work, we evaluated the effect of a new Co (II) complex, against promastigotes of L. amazonensis of strain WHOM / BR / 75 / Josefa. Transmission electron microscopy (TEM) was performed to evaluate the parasite's ultrastructure and confocal laser microscopy to check for death by autophagy of the parasite. The complex was able to induce ultrastructural changes in the parasite, such as the formation of autophagic vacuoles near the pouch region flagellar and myelin figure formations. Finally, tests with anti-LC3B labeling indicated the possible death of the parasite by autophagy

Anti-toxoplasma gondii effect of metalocomplex compounds N0414 and N5814 / Efeito anti-toxoplasma gondii do composto metalocomplexo N0414 e N5814

Toxoplasma gondii, toxoplasmosis agent, is a obligate intracellular protozoan that is able of infecting a broad spectrum of vertebrate’s cells. Toxoplasmosis is a pathology related to severe damages to immunocompromised hosts and its current chemotherapy is quite restricted, being more used the combination of sulfadiazine and pyrimethamine, which is a therapy associated with adverse reactions. This fact highlights the importance of the study of new drugs against Toxoplasma gondii. Has been studied the biological effect of new metallocomplexe compounds, which are inorganic compounds that present promising biological activity as fungicide, bactericide and antiviral. The metallocomplexes, dinuclear ferric compounds N0414 (Fe alfanaftol BMPA) and N5814 (Fe beta-naphthol BMPA) showed activity against Toxoplasma gondii in vitro and it was nontoxic to LLC-MK2 cells, being able to reduce the activity of crucial antioxidant enzymes for the defense of the parasite. In this project, it will be investigated the activities of compounds of the metallocomplexes family as the compounds coordinated to sulfadiazine as the nucleus compound of ferric N0414 and N5814, which showed anti-Toxoplasma gondii activities and were able to eliminate the infection in almost all host cells. In further steps, we will investigate what kind of death the parasite undergoes after the treatment with the compounds through the ultrastructure analysis and the usage of specific markers by fluorescence microscopy. The compounds will also be used in vivo tests with mouse models in the acute phase of toxoplasmosis to prove the efficacy of these compounds

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

Regulation of lung oxidative damage by endogenous superoxide dismutase in sepsis

Background: The purpose of this research is to study the relationship between superoxide dismutase (SOD) and lung redox state in an animal model of sepsis. Methods: Sepsis was induced in rats by the cecal ligation and perforation model (CLP). After 3, 6, and 12 h, CLP protein content and expression of SOD1, SOD2, and SOD3 were evaluated, and SOD activity was assessed. Oxidative damage was determined by quantifying nitrotyrosine content. Lung localization of SOD3 was performed by immunohistochemistry. The protective effect of a SOD mimetic on oxidative damage, inflammation, and lung permeability was assessed 12 and 24 h after sepsis induction. Results: Lung levels of SOD1 decreased 3 and 12 h after sepsis, but SOD2 and SOD3 increased, as well as SOD activity. These alterations were not associated with changes in sod gene expression. Nitrotyrosine levels increased 3 and 12 h after sepsis. The administration of a SOD mimetic decreased nitrotyrosine and proinflammatory cytokine levels and improved lung permeability. Conclusions: SOD2 and SOD3 increased after sepsis induction, but this was insufficient to protect the lung. Treatments based on SOD mimetics could have a role in lung injury associated with sepsis

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London