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1.
Environ Sci Technol ; 58(33): 14753-14763, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38984996

RESUMO

The global increase in wildfires, primarily driven by climate change, significantly affects air quality and health. Wildfire-emitted particulate matter (WFPM) is linked to adverse health effects, yet the toxicological mechanisms are not fully understood given its physicochemical complexity and the lack of spatiotemporal exposure data. This study focuses on the physicochemical characterization of WFPM from a Canadian wildfire in June 2023, which affected over 100 million people in the US Northeast, particularly around New Jersey/New York. Aerosol systems were deployed to characterize WFPM during the 3 day event, revealing unprecedented mass concentrations mainly in the WFPM0.1 and WFPM0.1-2.5 size fractions. Peak WFPM2.5 concentrations reached 317 µg/m3, nearly 10 times the National Ambient Air Quality Standard (NAAQS) 24 h average limit. Chemical analysis showed a high organic-to-total carbon ratio (96%), consistent with brown carbon wildfires nanoparticles. Large concentrations of high-molecular-weight PAHs were found predominantly bound to WFPM0.1, with retene, a molecular marker of biomass burning and a known teratogen, being the most abundant (>70%). Computational modeling estimated a total lung deposition of 9.15 mg over 72 h, highlighting the health risks of WFPM, particularly due to its long-distance travel capability and impact on densely populated areas.


Assuntos
Material Particulado , Incêndios Florestais , New Jersey , Material Particulado/análise , Cidade de Nova Iorque , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Quebeque , Poluição do Ar , Canadá , Hidrocarbonetos Policíclicos Aromáticos/análise
2.
Rheumatology (Oxford) ; 61(8): 3123-3131, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34849627

RESUMO

OBJECTIVE: Systemic sclerosis (SSc) is characterized by vasculopathy, fibrosis of skin and internal organs, and autoimmunity with complications including interstitial lung disease, pulmonary hypertension, and digital ulcers with substantial morbidity and disability. Patients with SSc may require considerable healthcare resources with economic impact. The purpose of this systematic review was to provide a narrative synthesis of the economic impact and healthcare resource utilization associated with SSc. METHODS: MEDLINE and EMBASE were searched from inception to 20 January 2021. Studies were included if they provided information regarding the total, direct and indirect cost of SSc. The cost of SSc subtypes and associated complications was determined. Risk of bias assessments through the Joanna Briggs Institute cross-sectional and case series checklists, and the Newcastle-Ottawa Cohort and Case-Control study scales were performed. A narrative synthesis of included studies was planned. RESULTS: The number of publications retrieved was 1778, of which 34 were included representing 20 cross-sectional, 11 cohort, and three case-control studies. Studies used various methods of calculating cost including prevalence-based cost-of-illness approach and health resource units cost analysis. Overall SSc total annual cost ranged from USD $14 959 to $23 268 in USA, CAD $10 673 to $18 453 in Canada, €4607 to €30 797 in Europe, and AUD $7060 to $11 607 in Oceania. Annual cost for SSc-associated interstitial lung disease and pulmonary hypertension was USD $31 285-55 446 and $44 454-63 320, respectively. CONCLUSION: Cost-calculation methodology varied greatly between included studies. SSc represents a significant patient and health resource economic burden. SSc-associated complications increase economic burden and are variable depending on geographical location and access.


Assuntos
Hipertensão Pulmonar , Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Estudos de Casos e Controles , Efeitos Psicossociais da Doença , Estudos Transversais , Estresse Financeiro , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Doenças Pulmonares Intersticiais/complicações , Aceitação pelo Paciente de Cuidados de Saúde , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/terapia
3.
Indoor Air ; 32(4): e13029, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35481935

RESUMO

Individuals with COVID-19 who do not require hospitalization are instructed to self-isolate in their residences. Due to high secondary infection rates in household members, there is a need to understand airborne transmission of SARS-CoV-2 within residences. We report the first naturalistic intervention study suggesting a reduction of such transmission risk using portable air cleaners (PACs) with HEPA filters. Seventeen individuals with newly diagnosed COVID-19 infection completed this single-blind, crossover, randomized study. Total and size-fractionated aerosol samples were collected simultaneously in the self-isolation room with the PAC (primary) and another room (secondary) for two consecutive 24-h periods, one period with HEPA filtration and the other with the filter removed (sham). Seven out of sixteen (44%) air samples in primary rooms were positive for SARS-CoV-2 RNA during the sham period. With the PAC operated at its lowest setting (clean air delivery rate [CADR] = 263 cfm) to minimize noise, positive aerosol samples decreased to four out of sixteen residences (25%; p = 0.229). A slight decrease in positive aerosol samples was also observed in the secondary room. As the world confronts both new variants and limited vaccination rates, our study supports this practical intervention to reduce the presence of viral aerosols in a real-world setting.


Assuntos
Poluição do Ar em Ambientes Fechados , COVID-19 , Aerossóis , Poluição do Ar em Ambientes Fechados/análise , Humanos , RNA Viral , SARS-CoV-2 , Método Simples-Cego
4.
Acta Anaesthesiol Scand ; 66(1): 3-16, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34514595

RESUMO

BACKGROUND: Bleeding is the leading cause of maternal mortality in the world. Tranexamic acid reduces bleeding in trauma and surgery. Several systematic reviews of randomized trials have investigated tranexamic acid in the prevention of bleeding in cesarean delivery. However, the conclusions from systematic reviews are conflicting. This overview aims to summarize the evidence and explore the reasons for conflicting conclusions across the systematic reviews. METHODS: A comprehensive literature search of Medline, Embase, and Cochrane Database of Systematic Reviews was conducted from inception to April 2021. Screening, data extraction, and quality assessments were performed by two independent reviewers. A Measurement Tool to Assess Reviews 2 and the Risk of Bias Assessment Tool for Systematic Reviews were used for study appraisal. A qualitative synthesis of evidence is presented. RESULTS: In all, 14 systematic reviews were included in our analysis. Across these reviews, there were 32 relevant randomized trials. A modest reduction in blood transfusions and bleeding outcomes was found by most systematic reviews. Overall confidence in results varied from low to critically low. All of the included systematic reviews were at high risk of bias. Quality of evidence from randomized trials was uncertain. CONCLUSIONS: Systematic reviews investigating prophylactic tranexamic acid in cesarean delivery are heterogeneous in terms of methodological and reporting quality. Tranexamic acid may reduce blood transfusion and bleeding outcomes, but rigorous well-designed research is needed due to the limitations of the included studies. Data on safety and adverse effects are insufficient to draw conclusions.


Assuntos
Antifibrinolíticos , Ácido Tranexâmico , Antifibrinolíticos/uso terapêutico , Transfusão de Sangue , Feminino , Hemorragia , Humanos , Gravidez , Revisões Sistemáticas como Assunto , Ácido Tranexâmico/uso terapêutico
5.
Curr Opin Rheumatol ; 33(2): 122-127, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33481429

RESUMO

PURPOSE OF REVIEW: Systemic sclerosis (scleroderma, SSc) is a rare multisystem autoimmune disease characterized by autoantibodies, vasculopathy, and fibrosis of the skin and internal organs. This review aims to provide an overview and summary of the recent epidemiological studies in systemic sclerosis. RECENT FINDINGS: Global trends of scleroderma demonstrate greater prevalence of SSc in European, North, and South American patients compared with East Asian patients. However, the greatest prevalence (47 in 100 000), was found among the indigenous peoples in Canada. Phenotypical differences exist depending on the age of presentation with greater internal organ involvement and disease acceleration present in older patients. Sex differences include greater severity of disease expression, relative prevalence of diffuse cutaneous SSc, and organ involvement in males versus females. New studies conflict with previous data reporting greater proportion of pulmonary arterial hypertension in females. Furthermore, the effect of low median household income is demonstrated as a factor increasing risk of death in SSc patients. SUMMARY: Understanding the epidemiological factors in SSc enables patient care through patient classification, prognostication, and monitoring. Future research may emphasize enrichment of SSc patients in randomized trials who are more likely to progress or be treatment responsive, focused screening, and personalized patient care through the creation and validation of new SSc criteria and subsets.


Assuntos
Esclerodermia Localizada , Escleroderma Sistêmico , Idoso , Autoanticorpos , Feminino , Fibrose , Humanos , Masculino , Prevalência , Escleroderma Sistêmico/epidemiologia
6.
Amino Acids ; 53(10): 1635-1648, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34482475

RESUMO

The worrisome emergence of pathogens resistant to conventional drugs has stimulated the search for new classes of antimicrobial and antiparasitic agents from natural sources. Antimicrobial peptides (AMPs), acting through mechanisms that do not rely on the interaction with a specific receptor, provide new possibilities for the development of drugs against resistant organisms. This study sought to purify and proteomically characterize the antimicrobial and antiparasitic peptidomes of B. atrox and B. jararacussu snake venoms against Gram-positive (Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus-MRSA), Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae) bacteria, and the protozoan parasites Leishmania amazonensis and Plasmodium falciparum (clone W2, resistant to chloroquine). To this end, B. atrox and B. jararacussu venom peptides were purified by combination of 3 kDa cut-off Amicon® ultracentrifugal filters and reverse-phase high-performance liquid chromatography, and then identified by electrospray-ionization Ion-Trap/Time-of-Flight mass spectrometry. Fourteen distinct peptides, with masses ranging from 443.17 to 1383.73 Da and primary structure between 3 and 13 amino acid residues, were sequenced. Among them, 13 contained unique sequences, including 4 novel bradykinin-potentiating-like peptides (BPPs), and a snake venom metalloproteinase tripeptide inhibitor (SVMPi). Although commonly found in Viperidae venoms, except for Bax-12, the BPPs and SVMPi here reported had not been described in B. atrox and B. jararacussu venoms. Among the novel peptides, some exhibited bactericidal activity towards P. aeruginosa and S. aureus, had low hemolytic effect, and were devoid of antiparasitic activity. The identified novel antimicrobial peptides may be relevant in the development of new drugs for the management of multidrug-resistant Gram-negative and Gram-positive bacteria.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Venenos de Crotalídeos/química , Peptídeos/farmacologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antimaláricos/química , Antimaláricos/farmacologia , Bothrops , Venenos de Crotalídeos/isolamento & purificação , Hemolíticos/química , Hemolíticos/farmacologia , Humanos , Leishmania/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Peptídeos/química , Peptídeos/isolamento & purificação , Plasmodium falciparum/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Espectrometria de Massas por Ionização por Electrospray , Staphylococcus aureus/efeitos dos fármacos
7.
Environ Sci Technol ; 55(3): 1852-1863, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33476134

RESUMO

Exposure to bioaerosols has been implicated in adverse respiratory symptoms, infectious diseases, and bioterrorism. Although these particles have been measured within residential and occupational settings in multiple studies, the deposition of bioaerosol particles within the human respiratory system has been only minimally explored. This paper uses real-world environmental measurement data of total fungal spores using Air-o-Cell cassettes in 16 different apartments and residents' physiological data in those apartments to predict respiratory deposition of the spores. The airborne spore concentrations were measured during the spring, summer, and fall. The respiratory deposition of five most prevalent spore genera-Ascospores, Aspergillus, Basidiospores, Cladosporium, and Myxomycetes-was predicted using three empirical models: the Multiple Path Particle Dosimetry model, using both the Yeh and age-specific versions, and the Bioaerosol Adaptation of the International Committee on Radiological Protection's Lung deposition model. The predicted total deposited number of spores was highest for Ascospores and Cladosporium. While the majority of spores deposit were in the extrathoracic region, there is a significant deposition for both Aspergillus and Cladosporium in the alveolar region, potentially leading to the development of aspergillosis or allergic asthma. Although the dose-response relationship is unknown, the estimate of the actual spore deposition could be the first step in determining such a relationship.


Assuntos
Microbiologia do Ar , Cladosporium , Aspergillus , Monitoramento Ambiental , Humanos , Pulmão , Estações do Ano , Esporos Fúngicos
8.
Indoor Air ; 31(2): 502-523, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32931080

RESUMO

Bioaerosol concentrations in residential buildings located in the Northeastern US have not been widely studied. Here, in 2011-2015, we studied the presence and seasonal variability of culturable fungi and bacteria in three multi-family apartment buildings and correlated the bioaerosol concentrations with building ventilation system types and environmental parameters. A total of 409 indoor and 86 outdoor samples were taken. Eighty-five percent of investigated apartments had indoor-outdoor (I/O) ratios of culturable fungi below 1, suggesting minimal indoor sources of fungi. In contrast, 56% of the apartments had I/O ratios for culturable bacteria above 1, indicating the prominence of indoor sources of bacteria. Culturable fungi I/O ratios in apartments serviced by central heating, ventilation, and air-conditioning (HVAC) system were lower than those in apartments with window AC. The type of ventilation system did not have a significant effect on the presence of indoor culturable bacteria. A significant positive association was determined between indoor dew point (DP) levels and indoor culturable fungi (P < .001) and bacteria (P < .001), regardless of ventilation type. Also, residents in apartments with central HVAC did not experience extreme DP values. We conclude that building ventilation systems, seasonality, and indoor sources are major factors affecting indoor bioaerosol levels in residential buildings.


Assuntos
Microbiologia do Ar , Poluição do Ar em Ambientes Fechados , Monitoramento Ambiental , Ar Condicionado , Filtros de Ar , Bactérias , Fungos , Calefação , Habitação , Humanos , Material Particulado , Estações do Ano , Ventilação
9.
J Proteome Res ; 19(8): 3518-3532, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32686412

RESUMO

We report a structural and functional proteomics characterization of venoms of the two subspecies (Bothrops bilineatusbilineatus and B. b. smaragdinus) of the South American palm pit viper from the Brazilian state of Rondônia and B. b. smaragdinus from Perú. These poorly known arboreal and mostly nocturnal generalist predators are widely distributed in lowland rainforests throughout the entire Amazon region, where they represent an important cause of snakebites. The three B. bilineatus spp. venom samples exhibit overall conserved proteomic profiles comprising components belonging to 11 venom protein classes, with PIII (34-40% of the total venom proteins) and PI (8-18%) SVMPs and their endogenous tripeptide inhibitors (SVMPi, 8-10%); bradykinin-potentiating-like peptides (BBPs, 10.7-15%); snake venom serine proteinases (SVSP, 5.5-14%); C-type lectin-like proteins (CTL, 3-10%); phospholipases A2 (PLA2, 2.8-7.6%); cysteine-rich secretory proteins (CRISP, 0.9-2.8%); l-amino acid oxidases (LAO, 0.9-5%) representing the major components of their common venom proteomes. Comparative analysis of the venom proteomes of the two geographic variants of B. b. smaragdinus with that of B. b. bilineatus revealed that the two Brazilian taxa share identical molecules between themselves but not with Peruvian B. b. smaragdinus, suggesting hybridization between the geographically close, possibly sympatric, Porto Velho (RO, BR) B. b. smaragdinus and B. b. bilineatus parental populations. However, limited sampling does not allow determining the frequency of this event. The toxin arsenal of the South American palm pit vipers may account for the in vitro recorded collagenolytic, caseinolytic, PLA2, l-amino acid oxidase, thrombin-like and factor X-activating activities, and the clinical features of South American palm pit viper envenomings, i.e., local and progressively ascending pain, shock and loss of consciousness, spontaneous bleeding, and profound coagulopathy. The remarkable cross-reactivity of the Brazilian pentabothropic SAB antivenom toward the heterologous B. b. bilineatus venom suggests that the paraspecific antigenic determinants should have been already present in the venom of the last common ancestor of the Bothrops ″jararaca″ and ″taeniatus″ clades, about 8.5 Mya in the mid-late Miocene epoch of the Cenozoic era. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifiers PXD020043, PXD020026, and PXD020013.


Assuntos
Bothrops , Venenos de Crotalídeos , Crotalinae , Animais , Antivenenos , Proteoma/genética , Proteômica , Venenos de Víboras
10.
Phys Chem Chem Phys ; 22(22): 12678-12687, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32458928

RESUMO

Experimental and theoretical evidence points out the crucial role of specific intramolecular vibrational modes resonant with excitonic splittings in the interpretation of long-lived coherences observed in the two-dimensional spectra of some natural and synthetic light harvesting complexes. For the natural situation of illumination by incoherent (sun)light, the relevance of these vibrations is analyzed here for light-harvesting vibronic prototype dimers. The detailed analysis of the density matrix dynamics reveals that the inclusion of intramolecular vibrational modes reinforces the exciton coherence up to one order of magnitude and may increase the populations of lowest energy single exciton states, as well as populations and coherences in the site basis. In sharp contrast to the case of initial-state preparation by coherent (laser)light-sources, the initial thermal state of the local vibrational modes, as well as that of the anticorrelated vibrational mode, evolves devoid of non-classical correlations as confirmed by the absence of negative values of its phase-space quasi-probability distribution at all times. Therefore, not only the long-lived coherences observed in the two-dimensional spectra are induced by the coherent character of pulsed laser sources, but it is unambiguously shown here that the non-classical character generally assigned to the anticorrelated vibrational mode also comes as the result of the preparation of the initial state by coherent pulsed laser sources.

11.
Exp Parasitol ; 217: 107934, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32698075

RESUMO

The inadequacy of available treatments for leishmaniasis has presented up to 40% therapeutic failure. This fact suggests an urgency in the discovery of new drugs or alternative approaches for treating this disease. The objective of this study was to evaluate the antileishmanial activity of combined therapy between crotamine (CTA) from Crotalus durissus terrificus and the pentavalent antimonial Glucantime® (GLU). The assays were in vitro performed measuring the inhibition of Leishmania amazonensis amastigotes, followed by the evaluation of cellular production of cytokines and nitrites. After that, analytical methods were performed in order to characterize the molecules involved in the study by Mass Spectrometry, molecular affinity through an in silico assay and Surface Plasmon Resonance. In vivo experiments with BALB/c mice were performed by analyzing parasitemia, lesion size and immunological mediators. In the in vitro experiments, the pharmacological association improved the inhibition of the amastigotes, modulated the production of cytokines and nitric oxide. The therapy improved the effectiveness of the GLU, demonstrating a decreased parasitemia in the infected tissues. Altogether, the results suggest that the combined approach with CTA and GLU may be a promising alternative for the treatment of cutaneous leishmaniasis.


Assuntos
Antiprotozoários/uso terapêutico , Venenos de Crotalídeos/uso terapêutico , Crotalus , Leishmania mexicana/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Antimoniato de Meglumina/uso terapêutico , Animais , Antiprotozoários/farmacologia , Venenos de Crotalídeos/farmacologia , Combinação de Medicamentos , Interleucina-12/sangue , Interleucina-12/metabolismo , Leishmania mexicana/isolamento & purificação , Linfonodos/parasitologia , Macrófagos Peritoneais , Espectrometria de Massas , Antimoniato de Meglumina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Simulação de Acoplamento Molecular , Óxido Nítrico/metabolismo , Nitritos/análise , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo
12.
Trop Med Int Health ; 21(1): 84-92, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26458237

RESUMO

OBJECTIVE: To describe the current situation of Chagas disease in Ecuador and to evaluate the impact of vector control for the period 2004-2014. METHODS: Since 2004, the Ministry of Public Health has formalized activities for the surveillance and control of Chagas disease and we analyzed here available records. RESULTS: More than 200 000 houses were surveyed, and 2.6% were found to be infested (95% CI: 2.6-2.7), and more than 51 000 houses were sprayed with residual insecticide, with important yearly variations. A total of 915 cases of T. cruzi infection were registered. The Amazon region is emerging as a high priority area, where nearly half of T. cruzi infection cases originate. The costal region and the southern highland valleys remain important high-risk area. Vector control efforts over the past 10 years have been effective in the coastal region, where T. dimidiata predominates, and resulted in important reductions in house infestation indices in many areas, even reaching negligible levels in some parishes. CONCLUSION: Vector efforts need to be sustained and expanded for the elimination of T. dimidiata to be feasible. Novel vector control interventions need to be designed to reduce intrusion by several triatomine species present in the Amazon region and southern Ecuador. Strong political commitment is needed to sustain current achievements and improve the national coverage of these programmes.

13.
Artigo em Inglês | MEDLINE | ID: mdl-26827743

RESUMO

Snake venom toxins are related not only in detention, death and the promotion of initial digestion of prey but also due to their different biochemical, structural and pharmacological effects they can result in new drugs. Among these toxins snake venom serine proteases (SVSPs) should be highlighted because they are responsible for inducing changes in physiological functions such as blood coagulation, fibrinolysis, and platelet aggregation. This article presents the first serine protease (SP) isolated from Bothrops brazili: BbrzSP-32. The new SP showed 36 kDa of relative molecular mass and its absolute mass was confirmed by mass spectrometry as 32,520 Da. It presents 79.48% identity when compared to other SVSPs and was able to degrade the α-chain of fibrinogen, in in vitro models, because of this it is considered a SVTLE-A. It showed dose-dependent activity in the process of degradation of fibrin networks demonstrating greater specificity for this activity when compared to its thrombolytic action. BbrzSP-32 demonstrated proteolytic activity on gelatin and chromogenic substrates for serine proteases and thrombin-like enzymes (S-2288 and S-2238 respectively), besides having coagulant activity on human plasma. After pre-incubation with PMSF and benzamidine the coagulant and proteolytic activities on the S-2288 and S-2238 substrates were reduced. BbrzSP-32 shows stability against pH and temperature variations, demonstrating optimum activity between 30 and 40 °C and in the pH range 7.5 to 8.5. A new SP with potential biotechnological application was isolated.


Assuntos
Venenos de Crotalídeos/química , Serina Proteases/isolamento & purificação , Sequência de Aminoácidos , Animais , Bothrops , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos , Serina Proteases/química
14.
Pharmacology ; 95(1-2): 78-86, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25633844

RESUMO

BACKGROUND/AIMS: To evaluate antileishmanial activity of crotamine, a toxin isolated from Crotalus durissus terrificus, in solution form and encapsulated in biodegradable microparticles in vitro. METHODS: Particles were analyzed on-chip by surface plasmon resonance and characterized by testing their diameters, zeta potential and encapsulation rate. The viability of promastigotes as well as murine macrophages was assessed. Furthermore, the phagocytic index was determined for macrophages, and cell supernatants were collected for the determination of TNF-α levels. An infection assay using Leishmania amazonensis-infected macrophages was also conducted. RESULTS: The diameters and zeta potential of control particles (1.35 µm; -12.3 mV) and of those containing crotamine (3.09 µm; -20.9 mV) were adequate for the assays conducted. Crotamine-loaded particles were better captured by macrophages than control particles (increase of 12% in the phagocytic index), leading to increased TNF-α levels (196 pg/ml), and they also induced a significant decrease in the numbers of amastigotes compared to infected macrophages only. CONCLUSION: The approach presented here opens the possibility of working with safe concentrations of encapsulated toxins to reach antileishmanial effects.


Assuntos
Antiprotozoários/farmacologia , Venenos de Crotalídeos/farmacologia , Leishmania/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Animais , Antiprotozoários/administração & dosagem , Venenos de Crotalídeos/administração & dosagem , Crotalus , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacologia , Ácido Láctico/química , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/microbiologia , Masculino , Camundongos Endogâmicos BALB C , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Fator de Necrose Tumoral alfa/metabolismo
15.
BMC Complement Altern Med ; 15(1): 420, 2015 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-26608735

RESUMO

BACKGROUND: The Combretum leprosum Mart. plant, popularly known as mofumbo, is used in folk medicine for inflammation, pain and treatment of wounds. From this species, it is possible to isolate three triterpenes: (3ß, 6ß, 16ß-trihydroxylup-20(29)-ene) called lupane, arjunolic acid and molic acid. In this study, through preclinical tests, the effect of lupane was evaluated on the cytotoxicity and on the ability to activate cellular function by the production of TNF-α, an inflammatory cytokine, and IL-10, an immuno regulatory cytokine was assessed. The effect of lupane on the enzymes topoisomerase I and II was also evaluated. METHODS: For this reason, peripheral blood mononuclear cells (PBMCs) were obtained and cytotoxicity was assessed by the MTT method at three different times (1, 15 and 24 h), and different concentrations of lupane (0.3, 0.7, 1.5, 6, 3 and 12 µg/mL). The cell function was assessed by the production of TNF-α and IL-10 by PBMCs quantified by specific enzyme immunoassay (ELISA). The activity of topoisomerases was assayed by in vitro biological assays and in silico molecular docking. RESULTS: The results obtained showed that lupane at concentrations below 1.5 µg/mL was not toxic to the cells. Moreover, lupane was not able to activate cellular functions and did not alter the production of IL-10 and TNF-α. Furthermore, the data showed that lupane has neither interfered in the action of topoisomerase I nor in the action of topoisomerase II. CONCLUSION: Based on preclinical results obtained in this study, we highlight that the compound studied (lupane) has moderate cytotoxicity, does not induce the production of TNF-α and IL-10, and does not act on human topoisomerases. Based on the results of this study and taking into consideration the reports about the anti-inflammatory and leishmanicidal activity of 3ß, 6ß, 16ß-trihydroxylup-20(29)-ene, we suggest that this compound may serve as a biotechnological tool for the treatment of leishmaniasis in the future.


Assuntos
Anti-Inflamatórios/toxicidade , Combretum , Leucócitos Mononucleares/efeitos dos fármacos , Triterpenos/toxicidade , Anti-Inflamatórios/farmacologia , DNA Topoisomerases/metabolismo , Flores , Humanos , Interleucina-10/biossíntese , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Triterpenos/farmacologia , Fator de Necrose Tumoral alfa/biossíntese
16.
J Microencapsul ; 32(5): 467-77, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26052723

RESUMO

Synthetic compounds derived from cinnamic acid were tested in cultures containing the promastigote form of Leishmania amazonensis and the dimethylsulphoxide solution of B2 compound (2.0 mg/mL) led to a 92% decrease of leishmania in 96 h of treatment. Then, different liposomal systems (diameters ∼200 nm) were prepared by the extrusion method in the presence and absence of compounds studied. DSC thermograms of the liposomes in the presence of these compounds caused changes in ΔH, Tm and ΔT1/2, compared to controls, indicating that there was an interaction of the compounds with the lipid bilayer. Assays with negatively charged liposomal systems containing these drugs in L. amazonensis cultures led to a 50-80% decrease in the number of leishmanias with a concentration to 100 times lower when compared to the B2 initial test. These liposomal systems are promoting more interaction and delivery of the compounds and proved to be an efficient, stable and promising system.


Assuntos
Antiprotozoários/química , Cinamatos/química , Leishmania/crescimento & desenvolvimento , Antiprotozoários/farmacologia , Cinamatos/farmacologia , Lipossomos
17.
J Phys Chem B ; 128(31): 7513-7519, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39052092

RESUMO

The interplay between electronic and intramolecular high-frequency vibrational degrees of freedom is ubiquitous in natural light-harvesting systems. Recent studies have indicated that an intramolecular vibrational donor-acceptor frequency difference can enhance energy transport. Here, we analyze the extent to which different intramolecular donor-acceptor vibrational frequencies affect excitation energy transport in the natural nonequilibrium steady state configuration. Comments are included on the less physical equilibrium case for comparison with the literature. It is found that for constant Huang-Rhys factors, whereas the acceptor population increases in the equilibrium case when the intramolecular vibrational frequency of the acceptor exceeds that of the donor, this increase is negligible for the nonequilibrium steady state. Therefore, these changes in acceptor population do not significantly enhance energy transport in the nonequilibrium steady state for the natural scenario of incoherent light excitation with biologically relevant parameters of typical photosynthetic complexes. Insight about a potential mechanism to optimize energy transfer in the nonequilibrium steady state based on increasing the harvesting time at the reaction center is analyzed.

18.
Aerosol Air Qual Res ; 24(1)2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38618024

RESUMO

Portable air cleaners (PACs) equipped with HEPA filters are gaining attention as cost-effective means of decreasing indoor particulate matter (PM) air pollutants and airborne viruses. However, the performance of PACs in naturalistic settings and spaces beyond the room containing the PAC is not well characterized. We conducted a single-blinded randomized cross-over interventional study between November 2020 and May 2021 in the homes of adults who tested positive for COVID-19. The intervention was air filtration with PAC operated with the HEPA filter set installed ("filter" condition) versus removed ("sham" condition, i.e., control). Sampling was performed in 29 homes for two consecutive 24-hour periods in the primary room (containing the PAC) and a secondary room. PAC effectiveness, calculated as reductions in overall mean PM2.5 and PM10 concentrations during the filter condition, were for the primary rooms 78.8% and 63.9% (n = 23), respectively, and for the secondary rooms 57.9% and 60.4% (n = 22), respectively. When a central air handler (CAH) was reported to be in use, filter-associated reductions of PM were statistically significant during the day (06:00-22:00) and night (22:01-05:59) in the primary rooms but only during the day in the secondary rooms. Our study adds to the literature evaluating the real-world effects of PACs on a secondary room and considering the impact of central air systems on PAC performance.

19.
Environ Sci Technol ; 47(22): 13077-85, 2013 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-24144266

RESUMO

Fuel additives incorporating nanosized ceria have been increasingly used in diesel engines as combustion promoters. However, few studies have assessed the impact of these nanotechnology-based additives on pollutant emissions. Here, we systematically compare emission rates of particulate and gaseous pollutants from a single-cylinder, four-cycle diesel engine using fuel mixes containing nanoceria of varying concentrations. The test fuels were made by adding different amounts of a commercial fuel additive Envirox into an ultralow-sulfur diesel fuel at 0 (base fuel), 0.1-, 1-, and 10-fold the manufacturer-recommended concentration of 0.5 mL Envirox per liter of fuel. The addition of Envirox resulted in ceria-concentration-dependent emission reductions of CO2, CO, total particulate mass, formaldehyde, acetaldehyde, acrolein, and several polycyclic aromatic hydrocarbons. These reductions at the manufacturer-recommended doping concentration, however, were accompanied by a substantial increase of certain other air pollutants, specifically the number of ultrafine particles (+32%), NO(x) (+9.3%), and the particle-phase benzo[a]pyrene toxic equivalence quotient (+35%). Increasing fuel ceria concentrations also led to decreases in the size of emitted particles. Given health concerns related to ultrafine particles and NO(x), our findings call for additional studies to further evaluate health risks associated with the use of nanoceria additives in various engines under various operating conditions.


Assuntos
Poluentes Atmosféricos/análise , Cério/química , Gases/análise , Gasolina/análise , Nanopartículas/química , Tamanho da Partícula , Material Particulado/análise , Emissões de Veículos/análise , Aerossóis/química , Aldeídos/análise , Dióxido de Carbono/análise , Monóxido de Carbono/análise , Óxidos de Nitrogênio/análise , Hidrocarbonetos Policíclicos Aromáticos/análise
20.
J Phys Chem Lett ; 14(6): 1436-1444, 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36734680

RESUMO

Oscillations in time-dependent two-dimensional electronic spectra appear as evidence of quantum coherence in light-harvesting systems related to electronic-vibrational resonant interactions. Nature, however, takes place in a non-equilibrium steady-state; therefore, the relevance of these arguments to the natural process is unclear. Here, we examine the role of intramolecular vibrations in the non-equilibrium steady-state of photosynthetic dimers in the natural scenario of incoherent light excitation. Specifically, we analyze the PEB dimer in the cryptophyte algae PE545 antenna protein. It is found that vibrations resonant with the energy difference between exciton states only marginally increase the quantum yield and the imaginary part of the intersite coherence that is relevant for transport compared to non-resonant vibrations in the natural non-equilibrium steady-state. That is, the electronic-vibrational resonance interaction does not significantly enhance energy transport under natural incoherent light excitation conditions.

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