Avaliação in silico de peptídeos antimicrobianos em plantas medicinais: uma abordagem por bioinformática

Antimicrobial peptides are found in a wide variety of living organisms, including medicinal plants. These are natural molecules and with activity against pathogenic and phytopathogenic bacteria. With growing microbial resistance heading into the post-antibiotic era, the exploration of these peptides by alternative methodologies using bioinformatics tools has become promising. The objective of this work was to prospect antimicrobial peptides from medicinal plants using bioinformatics tools for biotechnological applications. To verify the state of the art, searches were carried out for scientific articles in academic journals from 2018 to 2022. Bioinformatics analyzes were conducted in protein and peptide databases, NCBI, Uniprot/Swiss-Prot, CAMP and APD3 with the terms of the ten families of antimicrobial peptides. Predictions of physical-chemical and toxicity characteristics were performed using Expasy and ToxinPred software, respectively. Many scientific articles were obtained with the research theme, demonstrating the great relevance of the area. The peptides with the highest number of deposits in the databases of medicinal plants were defensins, heveins and knotins. One hevein stood out for its stability in its structure and did not show toxicity to mammalian cells. The study of these peptides can be useful in the design of synthetic molecules that can be exploited for biotechnological applications.Os peptídeos antimicrobianos são encontrados em uma grande diversidade de organismos vivos, incluindo as plantas medicinais. São moléculas naturais e com atividade contra bactérias patogênicas e fitopatogênicas. Com a crescente resistência microbiana rumo à era pós antibiótica, a exploração desses peptídeos por metodologias alternativas utilizando ferramentas de bioinformática se tornou promissora. O objetivo do trabalho foi prospectar peptídeos antimicrobianos de plantas medicinais utilizando ferramentas de bioinformática para aplicações biotecnológicas. Para a verificação do estado da arte foram realizadas buscas por artigos científicos em periódicos acadêmicos entre 2018 e 2022. Análises de bioinformática foram conduzidas em bancos de dados de proteínas e peptídeos, NCBI, Uniprot/Swiss-Prot, CAMP e APD3 com os termos das dez famílias de peptídeos antimicrobianos. As predições das características físico-químicas e toxicidade foram realizadas nos softwares Expasy e ToxinPred, respectivamente. Muitos artigos científicos foram obtidos com a temática da pesquisa, demonstrando grande relevância da área. Os peptídeos que apresentaram maior número de depósitos nos bancos de dados em plantas medicinais foram as defensinas, as heveínas e as knotinas. Uma heveína apresentou destaque quanto a estabilidade em sua estrutura e não apresentou toxicidade às células de mamíferos. O estudo desses peptídeos pode ser útil no design de moléculas sintéticas que possam ser exploradas para aplicações biotecnológicas

Saint or Sinner?: A Reconsideration of the Career of Prince Alexandre de Merode, Chair of the International Olympic Committee’s Medical Commission, 1967-2002

This article explores the role of Prince Alexandre de Merode in heading the IOC’s fight against drugs from the 1960s to 2002. History has not served de Merode very well. He has been presented in simplistic ways that emerge from context rather than evidence – as either a saint or a sinner. IOC-sanctioned accounts cast him in the mould of the saint: a moral and intelligent man who saved sports from doping. In contrast, sports academics have tended to portray him as a sinner: an ineffectual leader who did not develop either the testing systems or the punishments required to prevent doping and who deliberately concealed evidence of high-profile doping cases. This article assesses both representations before presenting information to support a richer and more complicated interpretation

H-alpha Survey of the Local Volume: Isolated Southern Galaxies

We present our H-alpha observations of 11 isolated southern galaxies: SDIG, PGC 51659, E 222-010, E 272-025, E 137-018, IC 4662, Sag DIG, IC 5052, IC 5152, UGCA 438, and E149-003, with distances from 1 to 7 Mpc. We have determined the total H-alpha fluxes from these galaxies. The star formation rates in these galaxies range from 10^{-1} (IC 4662) to 10^{-4}_{\odot}/yr (SDIG) and the gas depletion time at the observed star formation rates lies within the range from 1/6 to 24 Hubble times H_0^{-1} .Comment: 9 pages, 3 figure

Current epidemiology and outcome of infective endocarditis: A multicenter, prospective, cohort study

©2015 Wolters Kluwer Health, Inc.. This manuscript version is made available under the CC BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/. This document is the Published, version of a Published Work that appeared in final form in Medicine. To access the final edited and published work see https://doi.org/10.1097/MD.0000000000001816The aim of the study was to describe the epidemiologic and clinical characteristics and identify the risk factors of short-term and 1-year mortality in a recent cohort of patients with infective endocarditis (IE). From January 2008, multidisciplinary teams have prospectively collected all consecutive cases of IE, diagnosed according to the Duke criteria, in 25 Spanish hospitals. Overall, 1804 patients were diagnosed. The median age was 69 years (interquartile range, 55–77), 68.0% were men, and 37.1% of the cases were nosocomial or health care-related IE. Gram-positive microorganisms accounted for 79.3% of the episodes, followed by Gram-negative (5.2%), fungi (2.4%), anaerobes (0.9%), polymicrobial infections (1.9%), and unknown etiology (9.1%). Heart surgery was performed in 44.2%, and in-hospital mortality was 28.8%. Risk factors for in-hospital mortality were age, previous heart surgery, cerebrovascular disease, atrial fibrillation, Staphylococcus or Candida etiology, intracardiac complications, heart failure, and septic shock. The 1-year independent risk factors for mortality were age (odds ratio [OR], 1.02), neoplasia (OR, 2.46), renal insufficiency (OR, 1.59), and heart failure (OR, 4.42). Surgery was an independent protective factor for 1-year mortality (OR, 0.44). IE remains a severe disease with a high rate of in-hospital (28.9%) and 1-year mortality (11.2%). Surgery was the only intervention that significantly reduced 1-year mortality

Infective endocarditis in children and adolescents: a different profile with clinical implications

©2022 The author(s), under exclusive licence to the International Pediatric Research Foundation. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted, version of a Published Work that appeared in final form in Pediatric Research . To access the final edited and published work see https://doi.org/10.1038/s41390-022-01959-3BACKGROUND: Our aim was to compare pediatric infective endocarditis (IE) with the clinical profile and outcomes of IE in adults. METHODS: Prospective multicenter registry in 31 Spanish hospitals including all patients with a diagnosis of IE from 2008 to 2020. RESULTS: A total of 5590 patients were included, 49 were <18 years (0.1%). Congenital heart disease (CHD) was present in 31children and adolescents (63.2%). Right-sided location was more common in children/adolescents than in adults (46.9% vs. 6.3%, P < 0.001). Pediatric pulmonary IE was more frequent in patients with CHD (48.4%) than in those without (5.6%), P = 0.004.Staphylococcus aureus etiology tended to be more common in pediatric patients (32.7%) than in adults (22.3%), P = 0.082. Heart failure was less common in pediatric patients than in adults, due to the lower rate of heart failure in children/adolescents with CHD (9.6%) with respect to those without CHD (44.4%), P = 0.005. Inhospital mortality was high in both children, and adolescents and adults (16.3% vs. 25.9%; P = 0.126). CONCLUSIONS: Most IE cases in children and adolescents are seen in patients with CHD that have a more common right-sided location and a lower prevalence of heart failure than patients without CHD. IE in children and adolescents without CHD has a more similar profile to IE in adults

Four weeks versus six weeks of ampicillin plus ceftriaxone in Enterococcus faecalis native valve endocarditis: A prospective cohort study

Enterococcus faecalis infective endocarditis (EFIE) is a severe disease of increasing incidence. The objective was to analyze whether the outcome of patients with native valve EFIE (NVEFIE) treated with a short course of ampicillin plus ceftriaxone (4wAC) was similar to patients treated according to international guidelines (6wAC). Between January 2008 and June 2018, 1,978 consecutive patients with definite native valve IE were prospectively included in a national registry. Outcomes of patients with NVEFIE treated with 4wAC were compared to those of patients who received 6wAC. Three hundred and twenty-two patients (16.3%) had NVEFIE. One hundred and eighty-three (56.8%) received AC. Thirty-nine patients (21.3%) were treated with 4wAC for four weeks and 70 patients (38.3%) with 6wAC. There were no differences in age or comorbidity. Patients treated 6wAC presented a longer duration of symptoms before diagnosis (21 days, IQR 7-60 days vs. 7 days, IQR 1-22 days; p = 0.002). Six patients presented perivalvular abscess and all of these received 6wAC. Surgery was performed on 14 patients (35.9%) 4wAC and 34 patients (48.6%) 6wAC (p = 0.201). In-hospital mortality, one-year mortality and relapses among 4wAC and 6wAC patients were 10.3% vs. 11.4% (p = 0.851); 17.9% vs. 21.4% (p = 0.682) and 5.1% vs. 4.3% (p = 0.833), respectively. In conclusion, a four-week course of AC may be considered as an alternative regimen in NVEFIE, notably in patients with shorter duration of symptoms and those without perivalvular abscess. These results support the performance of a randomized clinical trial to evaluate the efficacy of this short regimen.This work was supported in part by the “Fondo de Investigaciones Sanitarias” (FIS) grant 17/01251 from the “Instituto de Salud Carlos III”, Madrid, Spain awarded to JMM. JMM received a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–19. JMP was member of the Endocarditis Team of the Hospital Clinic of Barcelona, Spain when this project was approved by the GAMES Steering Committee.

Enzimas marcadoras de indução de resistência diferencialmente reguladas em soja resistente e suscetível à ferrugem-asiática-da-soja.

O objetivo deste trabalho foi avaliar, por meio de enzimas marcadoras, a indução de resistência à ferrugem-asiática-da-soja em genótipos de soja contrastantes quanto à suscetibilidade a Phakopsora pachyrhizi. Aproteína total e as atividades de cinco enzimas marcadoras da indução de resistência (lipoxigenases, peroxidases, fenilalanina amônia-liase, quitinases e ?-1, 3-glucanases) foram avaliadas em extratos de folhas de plantas de soja dos genótipos Embrapa 48 (suscetível) e PI 561356 (resistente), submetidas à inoculação ou não com o patógeno. Foram observadas respostas de defesa discrepantes entre os dois genótipos e entre os tempos de coleta (12, 72 e 168 horas após inoculação). A resposta de indução dessas enzimas assemelha-se à defesa bifásica, para Embrapa 48, e é consistente com o observado para outros patossistemas. No entanto, o genótipo PI 561356 respondeu com diminuição da concentração de proteína total e das atividades enzimáticas, o que indica redução do metabolismo geral das plantas infectadas. Há um importante mecanismo de resistência do genótipo PI 561356, ainda não relatado, embasado em vias que envolvem essas enzimas marcadoras e em mecanismos que utilizam menor concentração de proteínas, como os de via metabólica de resposta em cascata. Differentially regulated induced resistance marker enzymes in soybean genotypes resistant and susceptible to Asian soybean rust. The objective of this work was to evaluate induced resistance to Asian soybean rust by means of enzyme activities in soybean genotypes contrasting as to their susceptibility to Phakopsora pachyrhizi. Total protein and the activities of five induced resistance marker enzymes (lipoxygenases, peroxidases, phenylalanine ammonia-lyase, chitinases and ?-1, 3-glucanases) were evaluated in leaf extracts of soybean plants of the genotypes Embrapa 48 (susceptible) and PI 561356 (resistant), inoculated or not with the pathogen. Discrepant defense responses were obtained between the two genotypes and among the leaf harvest times (12, 72, and 168 hours after inoculation). The induction response of these enzymes resembles the biphasic defense in Embrapa 48 and is consistent with that observed in other pathological systems. However, the genotype PI 561356 responded with a decrease in total protein concentration and in enzymatic activities, indicating a general reduction in the metabolism of the infected plants. There is an important mechanism of resistance for the genotype PI 561356, not yet reported, which is grounded on the metabolic ways involving these induced resistance marker enzymes and on the mechanisms that use lower concentrations of total protein, such as the ones with metabolic pathways in response cascade

Structurally Related Monoterpenes p-Cymene, Carvacrol and Thymol Isolated from Essential Oil from Leaves of Lippia sidoides Cham. (Verbenaceae) Protect Mice against Elastase-Induced Emphysema

Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes (p-cymene, carvacrol and thymol) isolated from essential oil from leaves Lippia sidoides Cham. (Verbenaceae). Methods: Mices received porcine pancreatic elastase (PPE) and were treated with p-cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated. Results: In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1 beta, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-kappa B-positive cells in lung parenchyma (p < 0.05). All treatments attenuated levels of 8-iso-PGF2 alpha but only thymol was able to reduced exhaled nitric oxide (p < 0.05). Conclusion: Monoterpenes p-cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Laboratorio de Investigacao Medica, Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo (LIM)Univ Fed Sao Paulo, Dept Biol Sci, BR-09913030 Diadema, BrazilUniv Sao Paulo, Sch Med, Dept Med, BR-01246903 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Exact Sci & Earth, BR-09913030 Diadema, BrazilFed Univ ABC, Ctr Nat Sci & Humanities, BR-09606045 Santo Andre, SP, BrazilUniv Fed Sao Paulo, Dept Biosci, Campus Baixada Santista, BR-11015020 Santos, SP, BrazilDepartment of Biological Science, Universidade Federal de São Paulo, Diadema 09913-030, BrazilDepartment of Exact Science and Earth, Universidade Federal de São Paulo, Diadema 09913-030, BrazilDepartment of Bioscience, Federal University of São Paulo, Campus Baixada Santista, Santos 11015-020, SP, BrazilCNPq: 300546/2012-2CNPq: 304465/2012-7CNPq: 476877/2012-1CNPq: 306278/2015-4FAPESP: 2011/51739-0FAPESP: 2013/02881-4FAPESP: 2008/55359-5FAPESP: 2015/11936-2FAPESP: 2014/25689-4LIM: LIM20Web of Scienc

Mural Endocarditis: The GAMES Registry Series and Review of the Literature

© 2021 The Author(s). This manuscript version is made available under the CC-BY-NC 4.0 license http://creativecommons.org/licenses/by-nc/4.0/. This document is the Acceptedversion of a Published Work that appeared in final form in Infectious Diseases and Therapy. To access the final edited and published work see https://doi.org/10.1007/s40121-021-00490-yIntroduction: Mural infective endocarditis (MIE) is a rare type of endovascular infection. We present a comprehensive series of patients with mural endocarditis. Methods: Patients with infectious endocarditis (IE) from 35 Spanish hospitals were prospectively included in the GAMES registry between 2008 and 2017. MIEs were compared to non-MIEs. We also performed a literature search for cases of MIE published between 1979 and 2019 and compared them to the GAMEs series. Results: Twenty-seven MIEs out of 3676 IEs were included. When compared to valvular IE (VIE) or device associated IE (DIE), patients with MIE were younger (median age 59 years, p \ 0.01). Transplantation (18.5% versus 1.6% VIE and 2% DIE, p \ 0.01), hemodialysis (18.5% versus 4.3% VIE and 4.4% DIE, p = 0.006), catheter source (59.3% versus 9.7% VIE and 8.8% DIE, p \ 0.01) and Candida etiology (22.2% versus 2% DIE and 1.2% VIE, p \ 0.01) were more common in MIE, whereas the Charlson Index was lower (4 versus 5 in non- MIE, p = 0.006). Mortality was similar.MIE from the literature shared many characteristics with MIE from GAMES, although patients were younger (45 years vs. 56 years, p \ 0.001), the Charlson Index was lower (1.3 vs. 4.3, p = 0.0001), catheter source was less common (13.9% vs. 59.3%) and there were more IVDUs (25% vs. 3.7%). S. aureus was the most frequent microorganism (50%, p = 0.035). Systemic complications were more common but mortality was similar. Conclusion: MIE is a rare entity. It is often a complication of catheter use, particularly in immunocompromised and hemodialysis patients. Fungal etiology is common. Mortality is similar to other IEs

Mural Endocarditis: The GAMES Registry Series and Review of the Literature

Introduction: Mural infective endocarditis (MIE) is a rare type of endovascular infection. We present a comprehensive series of patients with mural endocarditis. Methods: Patients with infectious endocarditis (IE) from 35 Spanish hospitals were prospectively included in the GAMES registry between 2008 and 2017. MIEs were compared to non-MIEs. We also performed a literature search for cases of MIE published between 1979 and 2019 and compared them to the GAMEs series. Results: Twenty-seven MIEs out of 3676 IEs were included. When compared to valvular IE (VIE) or device-associated IE (DIE), patients with MIE were younger (median age 59 years, p < 0.01). Transplantation (18.5% versus 1.6% VIE and 2% DIE, p < 0.01), hemodialysis (18.5% versus 4.3% VIE and 4.4% DIE, p = 0.006), catheter source (59.3% versus 9.7% VIE and 8.8% DIE, p < 0.01) and Candida etiology (22.2% versus 2% DIE and 1.2% VIE, p < 0.01) were more common in MIE, whereas the Charlson Index was lower (4 versus 5 in non-MIE, p = 0.006). Mortality was similar. MIE from the literature shared many characteristics with MIE from GAMES, although patients were younger (45 years vs. 56 years, p < 0.001), the Charlson Index was lower (1.3 vs. 4.3, p = 0.0001), catheter source was less common (13.9% vs. 59.3%) and there were more IVDUs (25% vs. 3.7%). S. aureus was the most frequent microorganism (50%, p = 0.035). Systemic complications were more common but mortality was similar. Conclusion: MIE is a rare entity. It is often a complication of catheter use, particularly in immunocompromised and hemodialysis patients. Fungal etiology is common. Mortality is similar to other IEs