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OBJECTIVE: Psoriatic arthritis (PsA) is chronic disease that compromises multiple domains and might be associated with progressive joint damage, increased mortality, functional limitation, and considerably impaired quality of life. Our objective was to generate evidence-based recommendations on the management of PsA in Pan American League of Associations for Rheumatology (PANLAR) countries. METHODS: We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach to adapt the 2019 recommendations of the European Alliance of Associations for Rheumatology. A working group consisting of rheumatologists from various countries in Latin America identified relevant topics for the treatment of PsA in the region. The methodology team updated the evidence and synthesized the information used to generate the final recommendations. These were then discussed and defined by a panel of 31 rheumatologists from 15 countries. RESULTS: Theses guidelines report 15 recommendations addressing therapeutic targets, use of antiinflammatory agents and corticosteroids, treatment with disease-modifying antirheumatic drugs (conventional synthetic, biologic, and targeted synthetic), therapeutic failure, optimization of biologic therapy, nonpharmacological interventions, assessment tools, and follow-up of patients with PsA. CONCLUSION: Here we present a set of recommendations to guide decision making in the treatment of PsA in Latin America, based on the best evidence available, considering resources, medical expertise, and the patient's values and preferences. The successful implementation of these recommendations should be based on clinical practice conditions, healthcare settings in each country, and a tailored evaluation of patients.
Assuntos
Antirreumáticos , Artrite Psoriásica , Reumatologia , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/terapia , Humanos , Antirreumáticos/uso terapêutico , Reumatologia/normas , Sociedades Médicas , América Latina , Medicina Baseada em Evidências , Qualidade de Vida , Anti-Inflamatórios/uso terapêutico , Corticosteroides/uso terapêuticoRESUMO
Endophytic bacteria found in marine macroalgae have been studied for their potential antimicrobial activity, consequently, they could serve as a valuable source of bioactive compounds to control pathogenic bacteria, yeasts, and fungi. Algae endophytic bacteria were isolated from Caulerpa sp., Ulva sp., Ahnfeltiopsis sp., and Chondracantus chamissoi from Yacila and Cangrejo Beaches (Piura, Peru). Antimicrobial assays against pathogenic bacteria were evaluated using cross-culture, over-plate, and volatile organic compound tests. Afterward, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of selected crude extracts were determined, also ITS molecular analysis, antifungal activity, and PCR of iturin, fengycin, and surfactin genes were performed for bacteria strains exhibiting better activity. Forty-six algae endophytic bacteria were isolated from algae. Ten strains inhibited gram-positive pathogenic bacteria (Enterococcus faecalis, Staphylococcus epidermidis, S. aureus, and Listeria monocytogenes), and 12 inhibited gram-negative bacteria (Escherichia coli and Salmonella enteric sv typhimurium). Bacteria with better activity belong to Bacillus sp., Kluyvera ascorbata, Pantoea agglomerans, Leclercia adecarboxylata, and Enterobacter sp., which only four showed antifungal activities against Candida albicans, C. tropicalis, Colletotrichium sp., Fusarium sp., Fusarium oxysporum, and Alternaria sp. Furthermore, K. ascorbata YAFE21 and Bacillus sp. YCFE4 exhibited iturin and fengycin genes. The results indicate that the algae endophytic bacteria found in this study, particularly K. ascorbata YAFE21, Bacillus sp. YCFR6, L. adecarboxylata CUFE2, Bacillus sp. YUFE8, Enterobacter sp. YAFL1, and P. agglomerans YAFL6, could be investigated as potential producers of antimicrobial compounds due to their broad activity against various microorganisms.
Assuntos
Endófitos , Testes de Sensibilidade Microbiana , Alga Marinha , Endófitos/isolamento & purificação , Endófitos/genética , Endófitos/metabolismo , Endófitos/química , Endófitos/classificação , Alga Marinha/microbiologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/classificação , Anti-Infecciosos/farmacologia , Anti-Infecciosos/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação , Antifúngicos/farmacologia , Antifúngicos/isolamento & purificação , Fungos/efeitos dos fármacos , Fungos/isolamento & purificação , Fungos/classificação , Bactérias Gram-Negativas/efeitos dos fármacos , Ulva/microbiologia , Caulerpa/microbiologia , Bactérias Gram-Positivas/efeitos dos fármacosRESUMO
BACKGROUND: There is a need for novel treatments for neuroblastoma, despite the emergence of new biological and immune treatments, since refractory pediatric neuroblastoma is still a medical challenge. Phyto cannabinoids and their hemisynthetic derivatives have shown evidence supporting their anticancer potential. The aim of this research was to examine Phytocannabinoids or hemisynthetic cannabinoids, which reduce the SHSY-5Y, neuroblastoma cell line's viability. METHODS: Hexane and acetyl acetate extracts were produced starting with Cannabis sativa L. as raw material, then, 9-tetrahidrocannabinol, its acid counterpart and CBN were isolated. In addition, acetylated derivatives of THC and CBN were synthesized. The identification and purity of the chemicals was determined by High Performance Liquid Chromatography and 1H y 13C Magnetic Nuclear Resonance. Then, the capacity to affect the viability of SHSY-5Y, a neuroblastoma cell line, was examined using the resazurin method. Finally, to gain insight into the mechanism of action of the extracts, phytocannabinoids and acetylated derivatives on the examined cells, a caspase 3/7 determination was performed on cells exposed to these compounds. RESULTS: The structure and purity of the isolated compounds was demonstrated. The extracts, the phytocannabinoids and their acetylated counterparts inhibited the viability of the SHSY 5Y cells, being CBN the most potent of all the tested molecules with an inhibitory concentration of 50 percent of 9.5 µM. CONCLUSION: Each of the evaluated molecules exhibited the capacity to activate caspases 3/7, indicating that at least in part, the cytotoxicity of the tested phytocannabinoids and their hemi-synthetic derivatives is mediated by apoptosis.
Assuntos
Canabinoides , Cannabis , Caspase 3 , Sobrevivência Celular , Neuroblastoma , Extratos Vegetais , Humanos , Cannabis/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Linhagem Celular Tumoral , Neuroblastoma/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 3/efeitos dos fármacos , Canabinoides/farmacologia , Canabinoides/química , Caspase 7/metabolismo , Apoptose/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Cromatografia Líquida de Alta PressãoRESUMO
Botrytis cinerea is a phytopathogenic fungus that causes serious damage to the agricultural industry by infecting various important crops. 2-allylphenol has been used in China as a fungicide for more than a decade, and it has been shown that is a respiration inhibitor. A series of derivatives of 2-allylphenol were synthesized and their activity against B. cinerea was evaluated by measuring mycelial growth inhibition. Results indicate that small changes in the chemical structure or the addition of substituent groups in the aromatic ring induce important variations in activity. For example, changing the hydroxyl group by methoxy or acetyl groups produces dramatic increases in mycelial growth inhibition, i.e., the IC50 value of 2-allylphenol decreases from 68 to 2 and 1 µg mL-1. In addition, it was found that the most active derivatives induce the inhibition of Bcaox expression in the early stages of B. cinerea conidia germination. This gene is associated with the activation of the alternative oxidase enzyme (AOX), which allows fungus respiration to continue in the presence of respiratory inhibitors. Thus, it seems that 2-allylphenol derivatives can inhibit the normal and alternative respiratory pathway of B. cinerea. Therefore, we believe that these compounds are a very attractive platform for the development of antifungal agents against B. cinerea.
Assuntos
Antifúngicos , Fungicidas Industriais , Antifúngicos/química , Fungicidas Industriais/química , BotrytisRESUMO
In this study, we aimed to evaluate two sets of sesquiterpene-aryl derivatives linked by an ester bond, their cytotoxic activities, and their capacity to activate caspases 3/7 and inhibit human topoisomerase I (TOP1). A total of 13 compounds were synthesized from the natural sesquiterpene (-)-drimenol and their cytotoxic activity was evaluated in vitro against three cancer cell lines: PC-3 (prostate cancer), HT-29 (colon cancer), MCF-7 (breast cancer), and an immortalized non-tumoral cell line (MCF-10). From the results, it was observed that 6a was the most promising compound due to its cytotoxic effect on three cancer cell lines and its selectivity, 6a was 100-fold more selective than 5-FU in MCF-7 and 20-fold in PC-3. It was observed that 6a also induced apoptosis by caspases 3/7 activity using a Capsase-Glo-3/7 assay kit and inhibited TOP1. A possible binding mode of 6a in a complex with TOP1-DNA was proposed by docking and molecular dynamics studies. In addition, 6a was predicted to have a good pharmacokinetic profile for oral administration. Therefore, through this study, it was demonstrated that the drimane scaffold should be considered in the search of new antitumoral agents.
Assuntos
Antineoplásicos , Sesquiterpenos , Humanos , Linhagem Celular Tumoral , DNA Topoisomerases Tipo I/metabolismo , Ésteres/farmacologia , Antineoplásicos/química , Sesquiterpenos/farmacologia , Apoptose , Caspases/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Proliferação de Células , Relação Estrutura-Atividade , Estrutura MolecularRESUMO
Recent studies have demonstrated the antiproliferative and cytotoxic effects of aza-steroids and steroidal sapogenins on human cancer cell lines. The scientific community has shown a growing interest in these compounds as drug candidates for cancer treatment. In the current work, we report the synthesis of new diosgenin oxime derivatives as potential antiproliferative agents. From (25 R)-5α-spirost-3,5,6-triol (1), a diosgenin derivative, ketones 2, 3, 4, and 9 were obtained and used as precursors of the new oximes. A condensation reaction was carried out between the steroidal ketones (2, 3, 4, and 9) with hydroxylamine hydrochloride in 2,4,6-trimethylpyridine to produce five spirostanic oximes (four of them are not reported before) with a 42-96% yield. Also, a new spirostanic α, ß-unsaturated cyanoketone was synthesized via Beckmann fragmentation using thionyl chloride with a 62% yield. Furthermore, we proposed a reaction mechanism with the aim of explaining such transformation.
Assuntos
Antineoplásicos , Diosgenina , Humanos , Cianocetona , Diosgenina/farmacologia , Esteroides/farmacologia , Antineoplásicos/farmacologia , Oximas/farmacologia , Cetonas/farmacologiaRESUMO
There has been minimal research linking the effects on racial-ethnic minorities' health outcomes, particularly research focused on racial-ethnic minorities seeking outpatient substance abuse treatment in the United States. The Great Recession from December 2007 to June 2009 in the United States provides the backdrop against the completion of substance abuse treatments among racial-ethnic minorities that may be associated with the impacts on users' social realities. We utilized data from the 2006-2011 Treatment Episode Datasets-Discharge (TEDS-D) dataset which collects data on outpatient substance abuse treatment institutions throughout the United States. The substance abuse treatment completion rates were higher prior to the Great Recession and lower following the Great Recession. Hispanics were more likely than non-Hispanic whites to complete substance abuse treatment, while other minority groups such as Non-Hispanic Blacks, were less likely to do so. Clients in the Northeast and West regions were more likely to successfully complete substance abuse treatment than those in the South. These findings have implications for impacting outpatient substance abuse treatment completion rates following the Great Recession to reduce racial-ethnic disparities which were impacted by region. Even amid an economic recession, treatment for substance abuse should continue to be a top concern.
RESUMO
Chile is in the extreme southwestern part of America, and it has an extreme length, of approximately 4300 km that increases to 8000 km considering the Chilean Antarctic Territory. Despite the large extent of its coastal territory and the diversity of geographic environments and climates associated with Chilean coasts, the research on marine resources in Chile has been rather scarce. From marine organisms found in Chilean coastal waters, algae have been the most studied, since they contain a wide range of interesting secondary metabolites that have some structural traits that make them unique and uncharacteristic. Thus, a wide structural variety of natural products including terpenoids (monoterpenes, sesquiterpenes, diterpenes, and meroterpenoids), furanones, and C15-acetogenins have been isolated and identified. This review describes the existing literature on bioprospecting and exploration of secondary metabolites from Chilean coasts.
Assuntos
Organismos Aquáticos , Produtos Biológicos , Regiões Antárticas , Organismos Aquáticos/metabolismo , Produtos Biológicos/química , Bioprospecção , ChileRESUMO
Colorectal cancer (CRC) is one of the most lethal cancers worldwide. If detected on time, surgery can expand life expectations of patients up to five more years. However, if metastasis has grown deliberately, the use of chemotherapy can play a crucial role in CRC control. Moreover, the lack of selectivity of current anticancer drugs, plus mutations that occur in cancerous cells, demands the development of new chemotherapeutic agents. Several steroids have shown their potentiality as anticancer agents, while some other compounds, such as Taxol and its derivatives bearing a carbamate functionality, have reached the market. In this article, the synthesis, characterization, and antiproliferative activity of four steroidal carbamates on mouse colon carcinoma CT26WT cells are described. Carbamate synthesis occurred via direct reaction between diosgenin, its B-ring modified derivative, and testosterone with phenyl isocyanate under a Brønsted acid catalysis. All obtained compounds were characterized by 1H and 13C Nuclear Magnetic Resonance (NMR), High Resolution Mass Spectroscopy (HRMS); their melting points are also reported. Results obtained from antiproliferative activity assays indicated that carbamates compounds have inhibitory effects on the growth of this colon cancer cell line. A molecular docking study carried out on Human Prostaglandin E Receptor (EP4) showed a high affinity between carbamates and protein, thus providing a valuable theoretical explanation of the in vitro results.
Assuntos
Antineoplásicos , Carcinoma , Neoplasias do Colo , Animais , Antineoplásicos/química , Carbamatos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Esteroides/química , Relação Estrutura-AtividadeRESUMO
In this work, the antioxidant activity of the hydro-ethanolic extracts of the leaves, flowers, and aerial parts of Steiractinia aspera Cuatrec, both fresh and post-distillation, was evaluated by ABTS+·, FRAP, H2O2 and DPPH assays. The cytotoxic activity was evaluated in MCF-7, MCF-10A and HT-29 cell lines. The hydro-ethanolic extracts were obtained by matrix solid-phase dispersion (MSPD) and ultrasound-assisted solvent extraction (SE). The fresh-leaf MSPD extract had the highest antioxidant activity, and the post-distillation leaf ultrasound-assisted SE extract had the highest cytotoxicity in the MCF-7 breast cancer cell line, although not selective, which was evaluated by sulforhodamine B assay. On the other hand, ROS was evaluated by flow cytometry which showed that post-distillation leaf extract is pro-oxidant. Chlorogenic acid, kaempferol-3-glucoside and quercetin were found in the fresh leaves' extracts, according to HPLC-DAD. PLC-DAD permitted the isolation of p-coumaric acid, E-3-(4-(((E)-3-(3,4-dihydroxyphenyl) acryloyl) oxy)-3-hydroxyphenyl) acrylic acid and a diglucosylated derivative of ursolic acid, which were analyzed by 1H and 13C NMR. Our results suggest that the fresh leaf extract of Steiractinia aspera Cuatrec has potential use for antioxidant applications.
Assuntos
Antioxidantes , Extratos Vegetais , Antioxidantes/química , Antioxidantes/farmacologia , Etanol , Peróxido de Hidrogênio , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta , QuercetinaRESUMO
Brassinosteroids (BRs) are plant hormones that play an essential role in plant development and have the ability to protect plants against various environmental stresses, such as low and high temperature, drought, heat, salinity, heavy metal toxicity, and pesticides. Mitigation of stress effects are produced through independent mechanisms or by interaction with other important phytohormones. However, there are few studies in which this property has been reported for BRs analogs. Thus, in this work, the enhancement of drought stress tolerance of A. thaliana was assessed for a series of 2-deoxybrassinosteroid analogs. In addition, the growth-promoting activity in the Rice Lamina Inclination Test (RLIT) was also evaluated. The results show that analog 1 exhibits similar growth activity as brassinolide (BL; used as positive control) in the RLIT bioassay. Interestingly, both compounds increase their activities by a factor of 1.2-1.5 when they are incorporated to polymer micelles formed by Pluronic F-127. On the other hand, tolerance to water deficit stress of Arabidopsis thaliana seedlings was evaluated by determining survival rate and dry weight of seedlings after the recovery period. In both cases, the effect of analog 1 is higher than that exhibited by BL. Additionally, the expression of a subset of drought stress marker genes was evaluated in presence and absence of exogenous applied BRs. Results obtained by qRT-PCR analysis, indicate that transcriptional changes of AtDREBD2A and AtNCED3 genes were more significant in A. thaliana treated with analog 1 in homogeneous solution than in that treated with BL. These changes suggest the activation of alternative pathway in response to water stress deficit. Thus, exogenous application of BRs synthetic analogs could be a potential tool for improvement of crop production under stress conditions.
Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Arabidopsis/efeitos dos fármacos , Arabidopsis/fisiologia , Brassinosteroides/farmacologia , Secas , Reguladores de Crescimento de Plantas/farmacologia , Estresse Fisiológico , Brassinosteroides/química , Estrutura Molecular , Fenótipo , Desenvolvimento Vegetal , Reguladores de Crescimento de Plantas/química , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/metabolismoRESUMO
In order to survive in a hostile habitat, plants have to manage the available resources to reach a delicate balance between development and defense processes, setting up what plant scientists call a trade-off. Most of these processes are basically responses to stimuli sensed by plant cell receptors and are influenced by the environmental features, which can incredibly modify such responses and even cause changes upon both molecular and phenotypic level. Therefore, significant differences can be detected between plants of the same species living in different environments. The comprehension of plant growth-defense trade-offs from the molecular basis to the phenotypic expression is one of the fundamentals for developing sustainable agriculture, so with this review we intend to contribute to the increasing of knowledge on this topic, which have a great importance for future development of agricultural crop production.
Assuntos
Desenvolvimento Vegetal/fisiologia , Animais , Produtos Agrícolas/fisiologia , Ecossistema , HumanosRESUMO
Brassinosteroids are polyhydroxysteroids that are involved in different plants' biological functions, such as growth, development and resistance to biotic and external stresses. Because of its low abundance in plants, much effort has been dedicated to the synthesis and characterization of brassinosteroids analogs. Herein, we report the synthesis of brassinosteroid 24-nor-5ß-cholane type analogs with 23-benzoate function and 22,23-benzoate groups. The synthesis was accomplished with high reaction yields in a four-step synthesis route and using hyodeoxycholic acid as starting material. All synthesized analogs were tested using the rice lamina inclination test to assess their growth-promoting activity and compare it with those obtained for brassinolide, which was used as a positive control. The results indicate that the diasteroisomeric mixture of monobenzoylated derivatives exhibit the highest activity at the lowest tested concentrations (1 × 10-8 and 1 × 10-7 M), being even more active than brassinolide. Therefore, a simple synthetic procedure with high reaction yields that use a very accessible starting material provides brassinosteroid synthetic analogs with promising effects on plant growth. This exploratory study suggests that brassinosteroid analogs with similar chemical structures could be a good alternative to natural brassinosteroids.
Assuntos
Benzoatos/síntese química , Brassinosteroides/síntese química , Colanos/síntese química , Desenvolvimento Vegetal , Arabidopsis/crescimento & desenvolvimento , Benzoatos/química , Brassinosteroides/química , Colanos/química , Ácido Desoxicólico/síntese química , Ácido Desoxicólico/química , Estrutura Molecular , Oryza/química , Reguladores de Crescimento de Plantas , Esteroides Heterocíclicos/químicaRESUMO
A priority of modern agriculture is to use novel and environmentally friendly plant-growth promoter compounds to increase crop yields and avoid the indiscriminate use of synthetic fertilizers. Brassinosteroids are directly involved in the growth and development of plants and are considered attractive candidates to solve this problem. Obtaining these metabolites from their natural sources is expensive and cumbersome since they occur in extremely low concentrations in plants. For this reason, much effort has been dedicated in the last decades to synthesize brassinosteroids analogs. In this manuscript, we present the synthesis and characterization of seven steroidal carbamates starting from stigmasterol, ß-sitosterol, diosgenin and several oxygenated derivatives of it. The synthesis route for functionalization of diosgenin included epoxidation and epoxy opening reactions, reduction of carbonyl groups, selective oxidation of hydroxyl groups, among others. All the obtained compounds were characterized by 1H and 13C NMR, HRMS, and their melting points are also reported. Rice lamina inclination test performed at different concentrations established that all reported steroidal carbamates show plant-growth-promoting activity. A molecular docking study evaluated the affinity of the synthesized compounds towards the BRI1-BAK1 receptor from Arabidopsis thaliana and three of the docked compounds displayed a binding energy lower than brassinolide.
Assuntos
Arabidopsis/crescimento & desenvolvimento , Carbamatos , Simulação de Acoplamento Molecular , Oryza/crescimento & desenvolvimento , Reguladores de Crescimento de Plantas , Brassinosteroides/química , Carbamatos/síntese química , Carbamatos/química , Carbamatos/farmacologia , Reguladores de Crescimento de Plantas/síntese química , Reguladores de Crescimento de Plantas/química , Reguladores de Crescimento de Plantas/farmacologia , Esteroides Heterocíclicos/químicaRESUMO
The metabolism of brassinosteroid leads to structural modifications in the ring skeleton or the side alkyl chain. The esterification and glycosylation at C-3 are the most common metabolic pathways, and it has been suggested that conjugate brassinosteroids are less active or inactive. In this way, plants regulate the content of active brassinosteroids. In this work, the synthesis of brassinosteroid 24-norcholane type analogs conjugated at C-3 with benzoate groups, carrying electron donor and electron attractant substituents on the aromatic ring, is described. Additionally, their growth-promoting activities were evaluated using the Rice Lamina Inclination Test (RLIT) and compared with that exhibited by brassinolide (used as positive control) and non-conjugated analogs. The results indicate that at the lowest tested concentrations (10-8-10-7 M), all analogs conjugated at C-3 exhibit similar or higher activities than brassinolide, and the diasteroisomers with S configuration at C-22 are the more active ones. Increasing concentration (10-6 M) reduces the biological activities of analogs as compared to brassinolide.
Assuntos
Benzoatos/química , Brassinosteroides/síntese química , Oryza/efeitos dos fármacos , Reguladores de Crescimento de Plantas/síntese química , Benzoatos/farmacologia , Brassinosteroides/química , Brassinosteroides/farmacologia , Relação Dose-Resposta a Droga , Conformação Molecular , Oryza/metabolismo , Reguladores de Crescimento de Plantas/química , Reguladores de Crescimento de Plantas/farmacologia , EstereoisomerismoRESUMO
Botrytis cinerea is a ubiquitous fungus that affects hundreds of plants, resulting in economic losses to the horticulture and fruit industry. The search for new antifungal agents is a matter of current interest. Thus, in this work a series of geranylated phenols in which the side alkyl chain has been hydrated have been synthesized, and their activity against B. cinerea has been evaluated. The coupling of phenol and geraniol has been accomplished under microwave irradiation obtaining the highest reaction yields in the shortest reaction times. Hydration of the side chain was carried out in dioxane with p-toluenesulfonic acid polymer-bound as the catalyst. All synthesized compounds were tested against B. cinerea using the growth inhibition assay and EC50 values were determined. The results show that activity depends on the number and nature of functional groups in the phenol ring and hydration degree of the geranyl chain. The most active compound is 1,4-dihydroquinone with one hydroxyl group attached at the end of the alkyl chain. Results from a molecular docking study suggest that hydroxyl groups in the phenol ring and alkyl chain are important in the binding of compounds to the active site, and that the experimental antifungal activity correlates with the number of H-bond that can be formed in the binding site.
Assuntos
Antifúngicos/farmacologia , Botrytis/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Fenóis/farmacologia , Terpenos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Botrytis/crescimento & desenvolvimento , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Simulação de Acoplamento Molecular , Fenóis/síntese química , Fenóis/química , Relação Estrutura-Atividade , Succinato Desidrogenase/antagonistas & inibidores , Succinato Desidrogenase/química , Terpenos/síntese química , Terpenos/químicaRESUMO
A new myxozoan species belonging to the genus Henneguya was isolated from the serous membrane of the visceral cavity of the hognosed catfish Brochis multiradiatus from Peruvian Amazon. Whitish plasmodia, macroscopically visible, were found in four of the thirty examined fishes. Mature myxospores were ellipsoidal in shape in frontal view and had a total length of 44.5 ± 0.6 µm (43.9-45.1), spore body measured 18.7 ± 0.9 µm (16.8-19.6) in length, 7.1 ± 0.2 µm (6.6-7.4) in width and 5.5 ± 0.3 µm (4.9-5.6) in thickness. The two polar capsules were elongated and equal in size, measuring 9.1 ± 0.1 µm (8.8-9.4) in length and 1.7 ± 0.1 µm (1.6-1.8) in width, occupying half of the myxospore body. Polar tubules coiled in 10-11 turns perpendicular to the long axis of the polar capsule. The caudal appendage was not bifurcated and measured 25.8 ± 0.6 µm (24.7-26.5) in length. The sequencing of the 18S rDNA gene resulted in 1400 bp and this sequence did not match any of the myxozoans available in GenBank. Phylogenetic analysis placed the new species in a well-supported subclade of Henneguya spp. infecting callichthyid fishes, with Henneguya loretoensis being the closest species. This study is the first description of a myxozoan species, Henneguya multiradiatus n. sp. from a fish of the genus Brochis.
Assuntos
Peixes-Gato , Cnidários , Doenças dos Peixes , Myxozoa , Parasitos , Doenças Parasitárias em Animais , Animais , DNA Ribossômico/genética , Brânquias , Myxozoa/genética , Peru , FilogeniaRESUMO
PURPOSE OF REVIEW: Eosinophilic granulomatosis with polyangiitis (EGPA) represents a rare clinical entity, which is getting increasing attention and relevance in view of our better understanding and newer insights into its pathogenesis. Concomitantly better recognition and understanding of the immune pathophysiologic role of eosinophils provide a solid ground of their role on systemic inflammatory disorders and defense against infectious triggers, especially parasites. This review will focus on describing the physiopathology of eosinophils, as well as providing an in depth description of the natural history, clinical spectrum, and therapy of EGPA. RECENT FINDINGS: Several studies have aimed at finding useful biomarkers to monitor disease activity, and reported data have shown that eotaxin 3, IL25, IL33, and some eicosanoids to be promising options. Regarding therapeutic advances, recently published studies have revealed the efficacy of mepolizumab during induction and maintenance of EGPA. Recently published data confirmed earlier studies that the use of azathioprine during the induction phase is of no benefit during long-term follow-up. In addition, data from the REOVAS study, which uses rituximab, is still ongoing and apparently with promising results. Eosinophils are involved in several systemic inflammatory disorders, and recent gathered data provide support for their role in triggering EGPA. Better understanding of its pathophysiology should generate newer insights into the pathogenesis, biomarkers of disease activity, and therapeutic targets.
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Síndrome de Churg-Strauss , Eosinófilos/imunologia , Biomarcadores/análise , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/imunologia , Síndrome de Churg-Strauss/terapia , Humanos , Imunossupressores/uso terapêuticoRESUMO
PURPOSE OF REVIEW: To review the spectrum of vasculitides in HIV-infected patients and to identify the clinical features that characterize vasculitis in sero-positive HIV. RECENT FINDINGS: Epidemiological studies conducted in the post-HAART era described the rarity of vasculitis in the setting of HIV-infected patients. A study identified histopathological features such as leukocytoclastic vasculitis of the vasa vasorum and adventitial inflammation in the large artery pathology of HIV-positive patients compared with HIV-negative patients with critical lower limb ischemia. A recent retrospective cohort study reported that HIV-positive patients with LVV developed more vascular complications, responded less to antiretroviral therapy, and had worse outcome than HIV-negative patients with LVV. Vasculitides continue to be a rare disease in patients with HIV. The spectrum of vasculitis ranges from life-threatening conditions to relatively mild skin conditions. Recognizing vasculitis in the setting of HIV-positive patients is important because sometimes it require immunosuppressive treatment.
Assuntos
Infecções por HIV , Poliarterite Nodosa , Vasculite , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Estudos Retrospectivos , Vasculite/complicações , Vasculite/epidemiologiaRESUMO
A series of ten chalcones (7a-j) and five new dihydrochromane-chalcone hybrids (7k-o) were synthesized and identified using spectroscopic techniques (IR, NMR, and MS). All compounds were evaluated in vitro against the B. cinerea and M. fructicola phytopathogens that affect a wide range of crops of commercial interest. All compounds were tested against both phytopathogens using the mycelial growth inhibition test, and it was found that two and five compounds had similar activity to that of the positive control for B. cinerea (7a = 43.9, 7c = 45.5, and Captan®= 24.8 µg/mL) and M. fructicola (7a = 48.5, 7d = 78.2, 7e = 56.1, 7f = 51.8, 7n = 63.2, and Mystic®= 21.6 µg/mL), respectively. To understand the key chalcone structural features for the antifungal activity on B. cinerea and M. fructicola, we developed structure-activity models with good statistical values (r2 and q2 higher than 0.8). For B. cinerea, the hydrogen bonding donor and acceptor and the atomic charge on C5 modulate the mycelial growth inhibition activity. In contrast, dipole moment and atomic charge on C1' and the carbonyl carbon modify the inhibition activity for M. fructicola. These results allow the design of other compounds with activities superior to those of the compounds obtained in this study.