Characterization of the fragmentation mechanisms in electrospray ionization tandem mass spectrometry of chloroquinoline derivatives with larvicidal activity against Aedes aegypti.

RATIONALE: 4,7-Dichloroquinoline (DCQ) represents a group of synthetic molecules inspired by natural products with important roles in biological and biomedical areas. This work aimed to characterize DCQ and its derivatives by high-resolution electrospray ionization (ESI) mass spectrometry and tandem mass spectrometry (ESI-MS/MS), supported by theoretical calculations. Biological assays were carried out with DCQ and its derivatives to determine LC50 values against Aedes aegypti larvae. METHODS: Five DCQ derivatives were synthesized by using previously described protocols. ESI-MS/MS analyses were carried out with a quadrupole/time-of-flight and ion-trap instrument. The proposed gas-phase protonation sites and fragmentation were supported by density functional theory calculations. The larvicidal tests were performed with the Ae. aegypti Rockefeller strain, and the LC50 values were determined by employing five test concentrations. Larval mortality was determined after treatment for 48 h. RESULTS: DCQ bromides or aldehydes (C-3 or C-8 positions), as well as the trimethylsilyl derivative (C-3 position), were prepared. Detailed ESI-MS/MS data revealed heteroatom elimination through an exception to the even-electron rule, to originate open-shell species. Computational studies were used to define the protonation sites and fragmentation pathways. High activity of DCQ and its derivatives against Ae. aegypti larvae was demonstrated. CONCLUSION: Our results provided a well-founded characterization of the fragmentation reactions of DCQ and its derivatives, which can be useful for complementary studies of the development of a larvicidal product against Ae. aegypti.

Edible Plant Extracts against Aedes aegypti and Validation of a Piper nigrum L. Ethanolic Extract as a Natural Insecticide.

The Aedes aegypti mosquito significantly impacts public health, with vector control remaining the most efficient means of reducing the number of arboviral disease cases. This study screened the larvicidal and pupicidal activity of common edible plant extracts. Piper nigrum L. (black pepper) extract production was optimized using accelerated solvent extraction (ASE) and validated following regulatory requirements using HPLC-PDA analytical methodology to quantify its major component-piperine. Larvicidal activity was determined for the standardized P. nigrum fruit ethanol extract (LC50 1.1 µg/mL) and piperine standard (LC50 19.0 µg/mL). Furthermore, 9-day residual activity was determined for the extract (4 µg/mL) and piperine (60 µg/mL), with daily piperine quantification. Semi-field trials of solid extract formulations demonstrated 24-day activity against Ae. aegypti larvae. Thus, the standardized P. nigrum extract emerges as a potential candidate for insecticide development to control the arboviral vector.

In the screening of alternative insecticides to control Aedes aegytpti larvae 2-methylanthraquinone showed no genotoxicity and low toxicity to zebrafish (Danio rerio).

The threats posed by insecticide resistance to Aedes aegypti in the context of controlling dengue have led to an urgent search for an environmentally safer alternative chemical with more effective larvicidal properties. Among many molecules tested, 2-methylanthraquinone showed the lowest LC50 for A. aegypti in a previous study and the highest LC50 for zebrafish embryos. Embryos were exposed at concentrations of 1.0, 2.19, 4.78, 10.46, 22.87, 50.0 and 100.0 mg/L, and malformations and mortality were significantly observed only at the highest exposures of 50 and 100 mg/L after 96 h. Micronucleus test and comet assay in zebrafish adults were both negative after exposures at 6.25, 12.5, 25.0, 50.0 and 100.0 mg/L for 96 h. Several biochemical biomarkers were analyzed in adults, and 2-methylanthraquinone did not interfere with acetylcholinesterase activity. The lactate dehydrogenase activity was higher at concentrations of 25 and 100 mg/L. Glutathione-S-Transferase (GST) activities were tested in the gill and body (muscle tail). The gill was more sensitive than body for GST activity after exposure to 2-methylanthraquinone, showing the highest activities, and 2-methylanthraquinone showed low toxicity to a non-target organism.

SARS-CoV-2/DENV co-infection: a series of cases from the Federal District, Midwestern Brazil.

BACKGROUND: Since the novel coronavirus disease outbreak, over 179.7 million people have been infected by SARS-CoV-2 worldwide, including the population living in dengue-endemic regions, particularly Latin America and Southeast Asia, raising concern about the impact of possible co-infections. METHODS: Thirteen SARS-CoV-2/DENV co-infection cases reported in Midwestern Brazil between April and September of 2020 are described. Information was gathered from hospital medical records regarding the most relevant clinical and laboratory findings, diagnostic process, therapeutic interventions, together with clinician-assessed outcomes and follow-up. RESULTS: Of the 13 cases, seven patients presented Acute Undifferentiated Febrile Syndrome and six had pre-existing co-morbidities, such as diabetes, hypertension and hypopituitarism. Two patients were pregnant. The most common symptoms and clinical signs reported at first evaluation were myalgia, fever and dyspnea. In six cases, the initial diagnosis was dengue fever, which delayed the diagnosis of concomitant infections. The most frequently applied therapeutic interventions were antibiotics and analgesics. In total, four patients were hospitalized. None of them were transferred to the intensive care unit or died. Clinical improvement was verified in all patients after a maximum of 21 days. CONCLUSIONS: The cases reported here highlight the challenges in differential diagnosis and the importance of considering concomitant infections, especially to improve clinical management and possible prevention measures. Failure to consider a SARS-CoV-2/DENV co-infection may impact both individual and community levels, especially in endemic areas.

The Potential of Biologically Active Brazilian Plant Species as a Strategy to Search for Molecular Models for Mosquito Control.

Natural products are a valuable source of biologically active compounds and continue to play an important role in modern drug discovery due to their great structural diversity and unique biological properties. Brazilian biodiversity is one of the most extensive in the world and could be an effective source of new chemical entities for drug discovery. Mosquitoes are vectors for the transmission of dengue, Zika, chikungunya, yellow fever, and many other diseases of public health importance. These diseases have a major impact on tropical and subtropical countries, and their incidence has increased dramatically in recent decades, reaching billions of people at risk worldwide. The prevention of these diseases is mainly through vector control, which is becoming more difficult because of the emergence of resistant mosquito populations to the chemical insecticides. Strategies to provide efficient and safe vector control are needed, and secondary metabolites from plant species from the Brazilian biodiversity, especially Cerrado, that are biologically active for mosquito control are herein highlighted. Also, this is a literature revision of targets as insights to promote advances in the task of developing active compounds for vector control. In view of the expansion and occurrence of arboviruses diseases worldwide, scientific reviews on bioactive natural products are important to provide molecular models for vector control and contribute with effective measures to reduce their incidence.

Plant Natural Products for the Control of Aedes aegypti: The Main Vector of Important Arboviruses.

The mosquito species Aedes aegypti is one of the main vectors of arboviruses, including dengue, Zika and chikungunya. Considering the deficiency or absence of vaccines to prevent these diseases, vector control remains an important strategy. The use of plant natural product-based insecticides constitutes an alternative to chemical insecticides as they are degraded more easily and are less harmful to the environment, not to mention their lower toxicity to non-target insects. This review details plant species and their secondary metabolites that have demonstrated insecticidal properties (ovicidal, larvicidal, pupicidal, adulticidal, repellent and ovipositional effects) against the mosquito, together with their mechanisms of action. In particular, essential oils and some of their chemical constituents such as terpenoids and phenylpropanoids offer distinct advantages. Thiophenes, amides and alkaloids also possess high larvicidal and adulticidal activities, adding to the wealth of plant natural products with potential in vector control applications.

Discovery of the rapanone and suberonone mixture as a motif for leishmanicidal and antifungal applications.

Leishmaniasis and fungal infections are significant diseases impacting worldwide public health. Treatments have developed greatly over time, however, there is a necessity to discover less toxic drugs, which have greater efficacy and are more economically accessible. This work conducted a screening of Cerrado species extracts: Connarus suberosus Planch. (Connaraceae), Neea theifera Oerst. (Nyctaginaceae) and Myrcia linearifolia Cambess. (Myrtaceae) against Leishmania (Leishmania) amazonensis, dermatophytes and yeasts. Leishmanicidal and antifungal tests were conducted using MTT colorimetric assay and CLSI methodology, respectively. Connarus suberosus extracts presented the most promising results against the aforementioned microorganisms, which has not been described in the literature. The root bark EtOAc extract was selected for chemical fractionation resulting in a mixture of rapanone (1) and a previously unreported compound named as suberonone (2); a mixture of ß-sitosterol (3) and stigmasterol (4); oleic acid (5); geranilgeraniol (6); and two derivatives obtained from 1 and 2 mixture. The rapanone and suberonone mixture demonstrated a MIC of 15.62 µg/mL against Candida albicans ATCC 10231.

A neolignan from Connarus tuberosus as an allosteric GABAA receptor modulator at the neurosteroid binding site.

In a screening of a small library of extracts from plants of the Amazonian and Cerrado biomes, a hexane extract of Connarus tuberosus roots was found to significantly potentiate the GABA induced fluorescence in a fluorescence (FLIPR) assay in CHO cells stably expressing the α1ß2γ2 subtype of human GABAA receptors. With the aid of HPLC-based activity profiling the activity was linked to the neolignan connarin. In CHO cells the activity of connarin was not abolished by increasing concentrations of flumazenil, while the effect of diazepam was increased by increasing concentrations of connarin. The effect of connarin was abolished by pregnenolone sulfate (PREGS) in a concentration-dependent manner, and the effect of allopregnanolone was further increased by increasing concentrations of connarin. In a two-microelectrode voltage clamp assay with Xenopus laevis oocytes transiently expressing GABAA receptors composed of human α1ß2γ2S and α1ß2 subunits connarin potentiated the GABA-induced currents, with EC50 values of 1.2 ± 0.3 µM (α1ß2γ2S) and 1.3 ± 0.4 µM (α1ß2), and with a maximum enhancement of currents Emax of 1959 ± 70% (α1ß2γ2S) and 185 ± 48% (α1ß2). The activation induced by connarin was abolished by increasing concentrations of PREGS.

Neuroimaging assessment of pediatric cerebral changes associated with SARS-CoV-2 infection during pregnancy.

Background: SARS-CoV-2 infection and perinatal neurologic outcomes are still not fully understood. However, there is recent evidence of white matter disease and impaired neurodevelopment in newborns following maternal SARS-CoV-2 infection. These appear to occur as a consequence of both direct viral effects and a systemic inflammatory response, with glial cell/myelin involvement and regional hypoxia/microvascular dysfunction. We sought to characterize the consequences of maternal and fetal inflammatory states in the central nervous system of newborns following maternal SARS-CoV-2 infection. Methods: We conducted a longitudinal prospective cohort study from June 2020 to December 2021, with follow-up of newborns born to mothers exposed or not exposed to SARS-CoV-2 infection during pregnancy. Brain analysis included data from cranial ultrasound scans (CUS) with grayscale, Doppler studies (color and spectral), and ultrasound-based brain elastography (shear-wave mode) in specific regions of interest (ROIs): deep white matter, superficial white matter, corpus callosum, basal ganglia, and cortical gray matter. Brain elastography was used to estimate brain parenchymal stiffness, which is an indirect quantifier of cerebral myelin tissue content. Results: A total of 219 single-pregnancy children were enrolled, including 201 born to mothers exposed to SARS-CoV-2 infection and 18 from unexposed controls. A neuroimaging evaluation was performed at 6 months of adjusted chronological age and revealed 18 grayscale and 21 Doppler abnormalities. Predominant findings were hyperechogenicity of deep brain white matter and basal ganglia (caudate nuclei/thalamus) and a reduction in the resistance and pulsatility indices of intracranial arterial flow. The anterior brain circulation (middle cerebral and pericallosal arteries) displayed a wider range of flow variation than the posterior circulation (basilar artery). Shear-wave US elastography analysis showed a reduction in stiffness values in the SARS-CoV-2 exposed group in all analyzed regions of interest, especially in the deep white matter elasticity coefficients (3.98 ± 0.62) compared to the control group (7.76 ± 0.77); p-value < 0.001. Conclusion: This study further characterizes pediatric structural encephalic changes associated with SARS-CoV-2 infection during pregnancy. The maternal infection has been shown to be related to cerebral deep white matter predominant involvement, with regional hyperechogenicity and reduction of elasticity coefficients, suggesting zonal impairment of myelin content. Morphologic findings may be subtle, and functional studies such as Doppler and elastography may be valuable tools to more accurately identify infants at risk of neurologic damage.

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study.

Introduction: SARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators. Methods: A sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array. Results: In the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester. Discussion and conclusion: From an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women.

Antifungal Activity of the Essential Oils of Callitris neocaledonica and C. sulcata Heartwood (Cupressaceae).

Mortality due to fungal infections has increased substantially, becoming a worldwide problem in public health. As a contribution to the discovery of new antifungal agents, the properties of the heartwood essential oils of two trees growing in New Caledonia, Callitris neocaledonica and C. sulcata (Cupressaceae) were investigated. The essential oils extracted by hydrodistillation were characterized by GC-FID and GC/MS analyses. From C. neocaledonica oil, 31 constituents were identified, representing 97.0% of the total oil composition, which was mainly constituted by oxygenated sesquiterpenes (88%). Among them, guaiol (1; 30.2%), bulnesol (2; 12.5%), α-eudesmol (3; 10.5%), ß-eudesmol (4; 10.5%), γ-eudesmol (10.2%), and elemol (4.9%) predominated. The chemical composition of C. sulcata oil, from which 39 constituents were identified (96.8% of the total oil composition), showed some similarities with that of C. neocaledonica oil. The major constituents were also oxygenated sesquiterpenes, accounting for 78.5% of the oil, amongst them, mainly compounds 1 (16.1%), 3 and 4 (9.7% each), as well as 2 (7.4%). The antifungal activity of the oils against clinical isolates of four dermatophytic fungi (Trichophyton mentagrophytes, T. rubrum, Microsporum canis, and M. gypseum) and six yeasts (Candida albicans, C. parapsilosis, C. glabrata, C. krusei, Cryptococcus neoformans, and Cryptococcus gattii) was tested by determining minimum inhibitory concentrations (MICs) using the microdilution method. The best antifungal activities of the C. neocaledonica and C. sulcata oils were obtained against C. krusei (MICs of 3.9 and 0.975 µg/ml, resp.). These MIC values were similar to those of the reference drugs itraconazole and fluconazole (1.0 and 0.5 mg/ml, resp.). The oils were also subjected to a screening for their possible DPPH(.) (2,2-diphenyl-1-picrylhydrazyl) radical-scavenging activity. C. neocaledonica essential oil was more active than C. sulcata oil (93.3 vs. 32.2% DPPH(.) scavenged at 250 µg/ml).

Combining chemometric and phytochemical tools to isolate and characterize activity of Vismia gracilis compounds against Aedes aegypti.

Vismia gracilis extracts were tested against Aedes aegypti to assess mortality and behavioural effects. The leaf hexanic extract (L-Hex) presented increased larvicidal activity with exposure period: LC50 46.48 µg/mL (24 h) and LC50 20.57 µg/mL (48 h). Eight compounds were annotated/isolated from the L-Hex active extract, 4 benzophenones and 4 anthraquinones. Considering chemometric findings, the benzophenone moiety, tested as the commercial benzophenone, promoted larval mortality (LC50 16.35 µg/mL). Both the L-Hex extract and benzophenone induced intestinal damage in larvae. Benzophenone also promoted toxicity and behavioural effects in female adults. These findings highlighted the potential use of this class of compounds for developing vector-control products.

Negative impact of SARS-CoV-2 infection in acute coronary syndrome mortality in a Latin American cohort study.

Purpose: COVID-19 infection has been associated with a high risk of complications and death among patients with acute coronary syndrome (ACS). However, there is little information on the simultaneous involvement in Latin American countries. Methods: In the period between May 2020 and February 2021, an observational, longitudinal, prospective cohort study with two parallel branches was conducted in private and public hospitals in Brasilia, Brazil, including patients with ACS with and without a positive SARS-CoV-2 test result during hospitalization. Results: A total of 149 patients with ACS were included (75 with COVID-19 and 74 controls). Patients with COVID-19 exhibited an average of 62 years of age, 57% men, 40% diabetics, 67% hypertensive, 48% had an ACS with ST-segment elevation, Killip I was predominant, a low Syntax Score in 72%, with an average Grace Score of 117, and a length of hospitalization of 43 days in average. The control branch was similar in clinical characteristics, except for a lower proportion of ST-segment elevation ACS (16%, p < 0.01) and a higher incidence of arrhythmias (8 vs. 20 %, p = 0.03). Using the Cox regression method of analysis of covariates collected in the study, it was identified that patients with COVID-19 had a risk of death 2.34 times higher than patients without COVID-19 (p = 0.049). Conclusion: In this study conducted in a Latin American capital, SARS-CoV-2 infection predicted a higher chance of death in patients admitted with ACS, which is a finding that reinforces the need for greater care when diseases develop in overlapping ways.

Impact of COVID-19 on the mental health of public university hospital workers in Brazil: A cohort-based analysis of 32,691 workers.

BACKGROUND: In early 2020, the COVID-19 pandemic paralyzed the world and exposed the fragility of health systems in the face of mass illness. Health professionals became protagonists, fulfilling their mission at the risk of physical and mental illness. The study aimed to evaluate absenteeism indirectly related to SARS-CoV-2 infection in a large population of health care professionals. METHODS: An observational longitudinal repeated measures study was performed, including workers linked to 40 public university hospitals in Brazil. All causes of absenteeism were analyzed, focusing on those not directly attributed to COVID-19. Results for the same population were compared over two equivalent time intervals: prepandemic and during the pandemic. FINDINGS: A total of 32,691 workers were included in the study, with health professionals comprising 82.5% of the sample. Comparison of the periods before and during the pandemic showed a 26.6% reduction in work absence for all causes, except for COVID-19 and mental health-related absence. Concerning work absence related to mental health, the odds ratio was 39.0% higher during the pandemic. At the onset of the pandemic, there was an increase in absenteeism (all causes), followed by a progressive reduction until the end of the observation period. INTERPRETATION: Work absence related to mental illness among health care professionals increased during the COVID-19 pandemic, highlighting the need for health care managers to prioritize and implement support strategies to minimize absenteeism.

Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients.

The present study applied distinct models of descriptive analysis to explore the integrative networks and the kinetic timeline of serum soluble mediators to select a set of systemic biomarkers applicable for the clinical management of COVID-19 patients. For this purpose, a total of 246 participants (82 COVID-19 and 164 healthy controls - HC) were enrolled in a prospective observational study. Serum soluble mediators were quantified by high-throughput microbeads array on hospital admission (D0) and at consecutive timepoints (D1-6 and D7-20). The results reinforce that the COVID-19 group exhibited a massive storm of serum soluble mediators. While increased levels of CCL3 and G-CSF were associated with the favorable prognosis of non-mechanical ventilation (nMV) or discharge, high levels of CXCL10 and IL-6 were observed in patients progressing to mechanical ventilation (MV) or death. At the time of admission, COVID-19 patients presented a complex and robust serum soluble mediator network, with a higher number of strong correlations involving IFN-γ, IL-1Ra and IL-9 observed in patients progressing to MV or death. Multivariate regression analysis demonstrates the ability of serum soluble mediators to cluster COVID-19 from HC. Ascendant fold change signatures and the kinetic timeline analysis further confirmed that the pairs "CCL3 and G-CSF" and "CXCL10 and IL-6" were associated with favorable or poor prognosis, respectively. A selected set of systemic mediators (IL-6, IFN-γ, IL-1Ra, IL-13, PDGF and IL-7) were identified as putative laboratory markers, applicable as complementary records for the clinical management of patients with severe COVID-19.

Cytotoxicity of δ-tocotrienols from Kielmeyera coriacea against cancer cell lines.

In the search for new anti-cancer compounds, Brazilian Cerrado plant species have been investigated. The hexane root bark extract of Kielmeyera coriacea lead to a mixture of δ-tocotrienol (1) and its dimer (2). The structures of both compounds 1 and 2 were established based on detailed 1D and 2D NMR and EI-MS analyses. The cytotoxicity of the mixture was tested against four human tumor cell lines in the following cultures: MDA-MB-435 (melanoma), HCT-8 (colon), HL-60 (leukemia), and SF-295 (glioblastoma), and displayed IC(50) values ranging from 8.08 to 23.58µg/mL. Additional assays were performed in order to investigate the mechanism of action of the mixture (1+2) against the human leukemia cell line HL-60. The results suggested that the mixture suppressed leukemia growth and reduced cell survival, triggering both apoptosis and necrosis, depending on the concentration.

Degradation evaluation and toxicity profile of bilobol, a promising eco-friendly larvicide.

Aedes aegypti is the main arbovirus vector transmitting chikungunya, Zika and dengue. The current vector control strategies are limited due to multiple insecticide resistance, deleterious impacts on the environment, and toxicity to non-target organisms. Bilobol, an alkylresorcinol isolated from the plant species Schinus terebinthifolia, demonstrated larvicidal activity against Aedes aegypti (LC50 7.67 mg/L in less than 24 h). To ensure that bilobol presents a viable alternative as an eco-friendly larvicide, this study aimed to explore the degradation process and acute toxicity of this alkylresorcinol in zebrafish, a non-target organism. A quantification method with validated parameters was developed and used to evaluate bilobol degradation in water over time. The Fish Embryo Toxicity (FET) test was applied to evaluate the acute toxicity of bilobol together with its degradation derivates. Results demonstrated that bilobol gradually degrades over time and almost completely disappears after 96 h, turning into small aliphatic chains which are less toxic than bilobol in its fundamental form. Therefore, it was possible to conclude that bilobol does not present significant toxicity to zebrafish embryos nor does it show signs of persistence in the environment. Additionally, bilobol can be found in high quantities not only in S. terebinthifolia, but also in cashew nut industry waste. Thus, bilobol constitutes an alternative environmentally friendly insecticide because it is not persistent, has indications of low toxicity to non-target organisms and presents a way to exploit massive quantities of material discarded by the food industry.

Molecular and Cellular Biomarkers of COVID-19 Prognosis: Protocol for the Prospective Cohort TARGET Study.

BACKGROUND: Since the beginning of the COVID-19 pandemic, the world's attention has been focused on better understanding the relation between the human host and the SARS-CoV-2 virus, as its action has led to hundreds of thousands of deaths. OBJECTIVE: In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation, and hemostasis, comparing mild and severe forms of COVID-19. METHODS: To accomplish these aims, we will analyze demographic characteristics, biochemical tests, immune biomarkers, leukocyte phenotyping, immunoglobulin profile, hormonal release (cortisol and prolactin), gene expression, thromboelastometry, neutralizing antibodies, metabolic profile, and neutrophil function (reactive oxygen species production, neutrophil extracellular trap production, phagocytosis, migration, gene expression, and proteomics). A total of 200 reverse transcription polymerase chain reaction-confirmed patients will be enrolled and divided into two groups: mild/moderate or severe/critical forms of COVID-19. Blood samples will be collected at different times: at inclusion and after 9 and 18 days, with an additional 3-day sample for severe patients. We believe that this information will provide more knowledge for future studies that will provide more robust and useful clinical information that may allow for better decisions at the front lines of health care. RESULTS: The recruitment began in June 2020 and is still in progress. It is expected to continue until February 2021. Data analysis is scheduled to start after all data have been collected. The coagulation study branch is complete and is already in the analysis phase. CONCLUSIONS: This study is original in terms of the different parameters analyzed in the same sample of patients with COVID-19. The project, which is currently in the data collection phase, was approved by the Brazilian Committee of Ethics in Human Research (CAAE 30846920.7.0000.0008). TRIAL REGISTRATION: Brazilian Registry of Clinical Trials RBR-62zdkk; https://ensaiosclinicos.gov.br/rg/RBR-62zdkk. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24211.

Evaluation of the antifungal potential of Brazilian Cerrado medicinal plants.

Therapeutic limitations, development of fungal drug resistance, drug-related toxicity, drug interactions and insufficient bioavailability of the currently available antifungal drugs have made the development of drugs necessary that would be able to treat the emerging fungal infections. The Cerrado is the second greater biome of Brazil and it was identified as one of the most distinguished biomes of South America, becoming an important source of innovative vegetal molecules to treat several conditions. Thus, the objective of this study was to evaluate the antifungal potential of Cerrado plants, mainly those used to treat infections and wounds. A total of 57 extracts were screened by the agar-well diffusion technique against Candida albicans and Trichophyton rubrum. The most promising extracts were tested in smaller concentrations and their minimal inhibitory concentrations (MIC) were determined by microdilution method. Results were analysed statistically by anova tests. Extracts of Kielmeyera coriacea, Renealmia alpinia, Stryphnodendron adstringens and Tabebuia caraiba were very active against T. rubrum, presented geometric means of the MIC values between 170.39 and 23.23 microg ml(-1). Extracts of Cerrado plants are of particular interest as source of new agents for the treatment of dermatophytic infections.

Trypanocidal activity of a new pterocarpan and other secondary metabolites of plants from Northeastern Brazil flora.

Two hundred fifteen compounds isolated from plants of Northeastern Brazil flora have been assayed against epimastigote forms of Trypanosoma cruzi, using the tetrazolium salt MTT as an alternative method. Eight compounds belonging to four different species: Harpalyce brasiliana (Fabaceae), Acnistus arborescens and Physalis angulata (Solanaceae), and Cordia globosa (Boraginaceae) showed significant activity. Among them, a novel and a known pterocarpan, a chalcone, four withasteroids, and a meroterpene benzoquinone were the represented chemical classes.