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1.
Anal Chem ; 96(19): 7460-7469, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38702053

RESUMO

Natural products (or specialized metabolites) are historically the main source of new drugs. However, the current drug discovery pipelines require miniaturization and speeds that are incompatible with traditional natural product research methods, especially in the early stages of the research. This article introduces the NP3 MS Workflow, a robust open-source software system for liquid chromatography-tandem mass spectrometry (LC-MS/MS) untargeted metabolomic data processing and analysis, designed to rank bioactive natural products directly from complex mixtures of compounds, such as bioactive biota samples. NP3 MS Workflow allows minimal user intervention as well as customization of each step of LC-MS/MS data processing, with diagnostic statistics to allow interpretation and optimization of LC-MS/MS data processing by the user. NP3 MS Workflow adds improved computing of the MS2 spectra in an LC-MS/MS data set and provides tools for automatic [M + H]+ ion deconvolution using fragmentation rules; chemical structural annotation against MS2 databases; and relative quantification of the precursor ions for bioactivity correlation scoring. The software will be presented with case studies and comparisons with equivalent tools currently available. NP3 MS Workflow shows a robust and useful approach to select bioactive natural products from complex mixtures, improving the set of tools available for untargeted metabolomics. It can be easily integrated into natural product-based drug-discovery pipelines and to other fields of research at the interface of chemistry and biology.


Assuntos
Produtos Biológicos , Descoberta de Drogas , Metabolômica , Software , Espectrometria de Massas em Tandem , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Produtos Biológicos/análise , Cromatografia Líquida/métodos , Fluxo de Trabalho
2.
Artigo em Inglês | MEDLINE | ID: mdl-38500290

RESUMO

INTRODUCTION: Bee venom has therapeutics and pharmacological properties. Further toxicological studies on animal models are necessary due to the severe allergic reactions caused by this product. METHOD: Here, Caenorhabditis elegans was used as an in vivo toxicity model, while breast cancer cells were used to evaluate the pharmacological benefits. The bee venom utilized in this research was collected from Apis mellifera species found in Northeast Brazil. The cytotoxicity caused by bee venom was measured by MTT assay on MDA-MB-231 and J774 A.1 cells during 24 - 72 hours of exposure. C. elegans at the L4 larval stage were exposed for three hours to M9 buffer or bee venom. Survival, behavioral parameters, reproduction, DAF-16 transcription factor translocation, the expression of superoxide dismutase (SOD), and metabolomics were analyzed. Bee venom suppressed the growth of MDA-MB-231 cancer cells and exhibited cytotoxic effects on macrophages. Also, decreased C. elegans survival impacted its behaviors by decreasing C. elegans feeding behavior, movement, and reproduction. RESULTS: Bee venom did not increase the expression of SOD-3, but it enhanced DAF-16 translocation from the cytoplasm to the nucleus. C. elegans metabolites differed after bee venom exposure, primarily related to aminoacyl- tRNA biosynthesis, glycine, serine and threonine metabolism, and sphingolipid and purine metabolic pathways. Our findings indicate that exposure to bee venom resulted in harmful effects on the cells and animal models examined. CONCLUSION: Thus, due to its potential toxic effect and induction of allergic reactions, using bee venom as a therapeutic approach has been limited. The development of controlled-release drug strategies to improve this natural product's efficacy and safety should be intensified.

3.
BMJ Open Respir Res ; 11(1)2024 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-38423952

RESUMO

INTRODUCTION: The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting COVID-19. Improved therapeutic strategies are urgently needed to better intervene particularly in severe cases of the disease. They should aim at controlling the hyperinflammatory state generated on infection, reducing lung tissue pathology and inhibiting viral replication. Previous research has pointed to a possible role for the chaperone HSP90 in SARS-CoV-2 replication and COVID-19 pathogenesis. Pharmacological intervention through HSP90 inhibitors was shown to be beneficial in the treatment of inflammatory diseases, infections and reducing replication of diverse viruses. METHODS: In this study, we investigated the effects of the potent HSP90 inhibitor Ganetespib (STA-9090) in vitro on alveolar epithelial cells and alveolar macrophages to characterise its effects on cell activation and viral replication. Additionally, the Syrian hamster animal model was used to evaluate its efficacy in controlling systemic inflammation and viral burden after infection. RESULTS: In vitro, STA-9090 reduced viral replication on alveolar epithelial cells in a dose-dependent manner and lowered significantly the expression of proinflammatory genes, in both alveolar epithelial cells and alveolar macrophages. In vivo, although no reduction in viral load was observed, administration of STA-9090 led to an overall improvement of the clinical condition of infected animals, with reduced oedema formation and lung tissue pathology. CONCLUSION: Altogether, we show that HSP90 inhibition could serve as a potential treatment option for moderate and severe cases of COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Triazóis , Cricetinae , Animais , Humanos , Mesocricetus , COVID-19/patologia , Pulmão/patologia
4.
Acta Neuropathol Commun ; 11(1): 193, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066589

RESUMO

The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also in many cases of post-infectious syndromes, colloquially referred to as "long COVID". Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues. In addition, complement system related proteins were more abundant in the serum of patients with PCS, matching observations on the transcriptomic level in the muscle tissue. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.


Assuntos
COVID-19 , Capilares , Humanos , SARS-CoV-2 , Músculo Esquelético , Fadiga
6.
3 Biotech ; 13(12): 391, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37953832

RESUMO

Clarisia racemosa Ruiz & Pav is a neotropical species found in humid forests from southern Mexico to southern Brazil. There are few studies related to the ethnopharmacological use of C. racemosa. Our objective was to evaluate the hydroalcoholic extract of C. racemosa as a potential antiparasitic agent. For this, we performed in vitro assays against strains of Leishmania amazonensis, Trypanosoma cruzi, Plasmodium falciparum, and Schistosoma mansoni. At the same time, immunomodulatory activity tests were carried out. The results demonstrated that the extract was able to stimulate and activate immune cells. In preliminary antiparasitic tests, structural modifications were observed in the promastigote form of L. amazonensis and in adult worms of S. mansoni. The extract was able to inhibit the growth of trypomastigote form of T. cruzi and finally showed low antiparasitic activity against strains of P. falciparum. It is pioneering work and these results demonstrate that C. racemosa extract is a promising alternative and contributes to the arsenal of possible forms of treatment to combat parasites. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03799-2.

7.
Lab Anim ; : 236772231194957, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37898111

RESUMO

Poorly designed preclinical studies may compromise human health due to erroneous conclusions regarding treatment effects in addition to contributing to experimental irreproducibility and wasted resources. Randomization is one of the crucial steps to enhance scientific rigor and is a commonly recognized bias-reducing instrument that increases the reliability and reproduction of studies involving animals (even with syngeneic animals). This procedure should be considered when planning a study and reported during data publication. In this context, this work aimed to highlight the importance of adopting quality measures in preclinical trials, with an emphasis on animal randomization. The 'Mouse Randomization' app was developed to help researchers estimate an adequate sample size to obtain significant statistical power, ensuring the ethical use of animals. This app is freely available on the internet to carry out animal randomization and calculate sample sizes for in vivo experiments. We believe that this brief discussion about animal randomization could raise awareness among researchers on how to improve the quality of preclinical research, increasing reproducibility and avoiding animal misuse.

8.
Chem Biodivers ; 20(8): e202300154, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37414744

RESUMO

Schistosomiasis affects about 260 million people worldwide and the search for new schistosomicidal compounds is urgent. In this study we evaluated the in vitro effect of barbatic acid against schistosomulae and young worms of Schistosoma mansoni. The barbatic acid was evaluated through the bioassay of motility and mortality, cellular viability and ultrastructural analysis of juvenile stages through Scanning Electron Microscopy. Barbatic acid showed a schistosomicidal effect against schistosomulae and young worms of S. mansoni after 3 h of exposure. At the end of 24 h, barbatic acid showed 100 %, 89.5 %, 52 % and 28.5 % of lethality for schistosomulae at the concentrations of 200, 100, 50 and 25 µM, respectively. For young worms, barbatic acid showed 100 % and 31.7 % of lethality at the concentrations of 200 and 100 µM, respectively. Motility changes were observed at all sublethal concentrations. There was a significant reduction in the viability of young worms after exposure to barbatic acid at 50, 100 and 200 µM. Extensive damage to the schistosomulae and young worm's tegument, was observed from 50 µM. This report provides data showing the schistosomicidal effect of barbatic acid on schistosomulae and young worms of S. mansoni, causing death, motility changes and ultrastructural damage to worms.


Assuntos
Anti-Helmínticos , Ácidos Ftálicos , Esquistossomicidas , Animais , Schistosoma mansoni , Anti-Helmínticos/farmacologia , Ácidos Ftálicos/farmacologia , Esquistossomicidas/farmacologia , Microscopia Eletrônica de Varredura
9.
J Appl Microbiol ; 134(7)2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37437916

RESUMO

AIMS: We investigated the putative fungistatic and fungicidal activities of pomegranate sarcotesta lectin (PgTeL) against Cryptococcus neoformans B3501 (serotype D), specifically the ability of PgTeL to inhibit yeast capsule and biofilm formation in this strain. METHODS AND RESULTS: PgTeL showed a minimum inhibitory concentration of 172.0 µg ml-1, at which it did not exhibit a fungicidal effect. PgTeL concentrations of 4.0-256.0 µg ml-1 reduced biofilm biomass by 31.0%-64.0%. Furthermore, 32.0-256.0 µg ml-1 PgTeL decreased the metabolic activity of the biofilm by 32.0%-93.0%. Scanning electron microscopy images clearly revealed disruption of the biofilm matrix. Moreover, PgTeL disrupted preformed biofilms. At concentrations of 8.0-256.0 µg ml-1, PgTeL reduced metabolic activity in C. neoformans by 36.0%-92.0%. However, PgTeL did not inhibit the ability of B3501 cells to form capsules under stress conditions. CONCLUSIONS: PgTeL inhibited biofilm formation and disrupted preformed biofilms, demonstrating its potential for use as an anticryptococcal agent.


Assuntos
Criptococose , Cryptococcus neoformans , Punica granatum , Lectinas/farmacologia , Punica granatum/metabolismo , Plâncton/metabolismo , Biofilmes , Testes de Sensibilidade Microbiana , Antifúngicos/farmacologia , Antifúngicos/metabolismo
10.
Microb Pathog ; 182: 106233, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37422173

RESUMO

Acinetobacter baumannii, a prominent emerging pathogen, is responsible for persistent and recurrent healthcare-associated infections (HAIs). Its bacterial resistance and virulence factors, such as biofilm formation, contribute to its survival in hospital environments. Combination therapy has proven to be an effective approach for controlling these infections; however, antimicrobial resistance and compound toxicity can hinder antimicrobial efficacy. Numerous in vitro studies have demonstrated the synergistic effect of antimicrobials and natural products against multidrug-resistant (MDR) A. baumannii biofilm. Riparin III, a natural alkamide derived from Aniba riparia (Nees) Mez., possesses various biological activities, including significant antimicrobial potential. Nonetheless, no reports are available on the use of this compound in conjunction with conventional antimicrobials. Hence, this study aimed to investigate the inhibition and eradication of A. baumannii MDR biofilm by combining riparin III and colistin, along with potential ultrastructural changes observed in vitro. Clinical isolates of A. baumannii, known for their robust biofilm production, were inhibited, or eradicated in the presence of the riparin III/colistin combination. Furthermore, the combination resulted in several ultrastructural alterations within the biofilm, such as elongated cells and coccus morphology, partial or complete disruption of the biofilm's extracellular matrix, and cells exhibiting cytoplasmic material extravasation. At the synergistic concentrations, the riparin III/colistin combination exhibited a low hemolytic percentage, ranging from 5.74% to 6.19%, exerting inhibitory and eradicating effects on the A. baumannii biofilm, accompanied by notable ultrastructural changes. These findings suggest its potential as a promising alternative for therapeutic purposes.

11.
Int J Mol Sci ; 24(11)2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37298243

RESUMO

The term "liver disease" refers to any hepatic condition that leads to tissue damage or altered hepatic function and can be induced by virus infections, autoimmunity, inherited genetic mutations, high consumption of alcohol or drugs, fat accumulation, and cancer. Some types of liver diseases are becoming more frequent worldwide. This can be related to increasing rates of obesity in developed countries, diet changes, higher alcohol intake, and even the coronavirus disease 2019 (COVID-19) pandemic was associated with increased liver disease-related deaths. Although the liver can regenerate, in cases of chronic damage or extensive fibrosis, the recovery of tissue mass is impossible, and a liver transplant is indicated. Because of reduced organ availability, it is necessary to search for alternative bioengineered solutions aiming for a cure or increased life expectancy while a transplant is not possible. Therefore, several groups were studying the possibility of stem cells transplantation as a therapeutic alternative since it is a promising strategy in regenerative medicine for treating various diseases. At the same time, nanotechnological advances can contribute to specifically targeting transplanted cells to injured sites using magnetic nanoparticles. In this review, we summarize multiple magnetic nanostructure-based strategies that are promising for treating liver diseases.


Assuntos
COVID-19 , Hepatopatias , Nanoestruturas , Humanos , Medicina Regenerativa , Hepatócitos/transplante , COVID-19/terapia , Hepatopatias/terapia , Células-Tronco , Regeneração Hepática , Fenômenos Magnéticos
12.
Acta Trop ; 245: 106965, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37295486

RESUMO

The present work aimed to carry out in vitro biological assays of thiazole compounds against adult worms of Schistosoma mansoni, as well as the in silico determination of pharmacokinetic parameters to predict the oral bioavailability of these compounds. In addition to presenting moderate to low cytotoxicity against mammalian cells, thiazole compounds are not considered hemolytic. All compounds were initially tested at concentrations ranging from 200 to 6.25 µM against adult worms of S. mansoni parasites. The results showed the best activity of PBT2 and PBT5 at a concentration of 200 µM, which caused 100% mortality after 3 h of incubation. While at 6 h of exposure, 100% mortality was observed at the concentration of 100 µM. Subsequent studies with these same compounds allowed classifying PBT5, PBT2, PBT6 and PBT3 compounds, which were considered active and PBT1 and PBT4 compounds, which were considered inactive. In the ultrastructural analysis the compounds PBT2 and PBT5 (200 µM) promoted integumentary changes with exposure of the muscles, formation of integumentary blisters, integuments with abnormal morphology and destruction of tubercles and spicules. Therefore, the compounds PBT2 and PBT5 are promising antiparasitics against S. mansoni.


Assuntos
Esquistossomose mansoni , Esquistossomicidas , Animais , Schistosoma mansoni/ultraestrutura , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Esquistossomicidas/farmacologia , Esquistossomicidas/uso terapêutico , Antiparasitários/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Mamíferos
13.
BMC Med Educ ; 23(1): 471, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37353802

RESUMO

BACKGROUND: Knowledge of pharmacology is crucial for physicians to perform rational and safe medicine. Medical professionals are responsible for prescribing drugs and a weak performace of those can result in medication errors leading to disability, hospitalization, and death, among other situations. It occurs worldwide, including in Brazil, so that learning pharmacology impacts on public health service. We aim to investigate the current pharmacology educational practices in medical schools in the state of Rio de Janeiro, Brazil. METHODS: We surveyed 14 of 22 medical schools in Rio de Janeiro. Pharmacology teachers (n=16) and medical students (n=89) answered a semi-structured questionnaire that included questions about the staff characteristics, pharmacology content, teacher's concepts, and common practices and resources that were used in pharmacology classes. RESULTS: Our results revealed that the medical schools had similar overall curriculums. Pharmacology teachers work more than 30hs a week (75%) and conducted both research and teaching (62.5%). We also found that the multimedia projector was the most common resource (71.9%), and passive pedagogical methodologies (e.g., expository classes) remain a current strategy in pharmacology classes (89.9%). In general, medical students are poorly motivated (55%), which may be related to their performance in assessments. In addition, students believe that pharmacology is a complex (52%) or very complex subject (46%) since for its full understanding the student needs concepts from other disciplines, which can have an impact on the performance and motivation of students. As a result, these medical students do not fully understand the integration between pharmacology's basic concepts and their clinical applications. CONCLUSION: These data seem to demonstrate that the adopted teaching and learning pharmacology strategies and methodologies can be improved in Rio de Janeiro.


Assuntos
COVID-19 , Farmacologia , Estudantes de Medicina , Humanos , Brasil , Pandemias , Aprendizagem , Ensino , Farmacologia/educação
14.
J Chem Inf Model ; 63(12): 3772-3785, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37129917

RESUMO

Confining molecular guests within artificial hosts has provided a major driving force in the rational design of supramolecular cages with tailored properties. Over the last 30 years, a set of design strategies have been developed that enabled the controlled synthesis of a myriad of cages. Recently, there has been a growing interest in involving in silico methods in this toolbox. Cavity shape and size are important parameters that can be easily accessed by inexpensive geometric algorithms. Although these algorithms are well developed for the detection of nonartificial cavities (e.g., enzymes), they are not routinely used for the rational design of supramolecular cages. In order to test the capabilities of this tool, we have evaluated the performance and characteristics of seven different cavity characterization software in the context of 22 analogues of well-known supramolecular cages. Among the tested software, KVFinder project and Fpocket proved to be the most software to characterize supramolecular cavities. With the results of this work, we aim to popularize this underused technique within the supramolecular community.


Assuntos
Algoritmos , Software
15.
Front Bioeng Biotechnol ; 11: 1108396, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37091338

RESUMO

The field of 3D bioengineering proposes to effectively contribute to the manufacture of artificial multicellular organ/tissues and the understanding of complex cellular mechanisms. In this regard, 3D cell cultures comprise a promising bioengineering possibility for the alternative treatment of organ function loss, potentially improving patient life expectancies. Patients with end-stage disease, for example, could benefit from treatment until organ transplantation or even undergo organ function restoration. Currently, 3D bioprinters can produce tissues such as trachea cartilage or artificial skin. Most low-cost 3D bioprinters are built from fused deposition modeling 3D printer frames modified for the deposition of biologically compatible material, ranging between $13.000,00 and $300.000,00. Furthermore, the cost of consumables should also be considered as they, can range from $3,85 and $100.000,00 per gram, making biomaterials expensive, hindering bioprinting access. In this context, our report describes the first prototype of a significantly low-cost 3D bioprinter built from recycled scrap metal and off-the-shelf electronics. We demonstrate the functionalized process and methodology proof of concept and aim to test it in different biological tissue scaffolds in the future, using affordable materials and open-source methodologies, thus democratizing the state of the art of this technology.

16.
Eur J Med Chem ; 254: 115310, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37062170

RESUMO

The present work reports the synthesis of a novel series of pyridine-thiazolidinones with anti-Trypanosoma cruzi and leishmanicidal activities (compounds 10-27), derived from 2 or 4-pyridine thiosemicarbazones (1-9). The in vitro assays were performed with Trypanosoma cruzi trypomastigotes and amastigotes, as well as with Leishmania amazonensis promastigotes and amastigotes. The cytotoxicity profile was evaluated using the cell line RAW 264.7. From the 18 pyridine-thiazolidinones, 5 were able to inhibit trypomastigotes. Overall, all compounds inhibited amastigotes, highlighting compounds 15 (0.60 µM), 18 (0.64 µM), 17 (0.81 µM), and 27 (0.89 µM). Compounds 15 and 18 were able to induce parasite cell death through necrosis induction. Analysis by scanning electron microscopy showed that T. cruzi trypomastigotes treated with compounds 15 and 18 induced morphological changes such as shortening, retraction and curvature of the parasite body and leakage of internal content. Regarding the antiparasitic evaluation against Leishmania amazonensis, only compound 27 had a higher selectivity compared to Miltefosine against the amastigote form (IC50 = 5.70 µM). Our results showed that compound 27 presented an antiparasitic activity for both Trypanosoma cruzi and Leishmania amazonensis. After in silico evaluation, it was suggested that the new pyridine-thiazolidinones had an appropriate drug-likeness profile. Our results pointed out a new chemical frame with an anti-Trypanosomatidae profile. The pyridine-thiazolidinones presented here for the first time could be used as a starting point for the development of new antiparasitic agents.


Assuntos
Doença de Chagas , Leishmania mexicana , Tripanossomicidas , Trypanosoma cruzi , Trypanosomatina , Humanos , Relação Estrutura-Atividade , Doença de Chagas/tratamento farmacológico , Antiparasitários/farmacologia , Tripanossomicidas/química
17.
Nat Microbiol ; 8(5): 860-874, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37012419

RESUMO

Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Cricetinae , Humanos , Vacinas Atenuadas , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Vacina BNT162 , Pandemias , Mesocricetus
18.
Exp Parasitol ; 248: 108455, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36764643

RESUMO

Schistosomiasis is an endemic disease in Brazil. It is important to broaden the treatment options to control and containment of the disease. Thiazolidine derivatives appear as important alternatives to treatment. In vitro studies have demonstrated excellent schistosomiasis activity for LPSF/GQ-238. The molecule, however, has poorly water-soluble. This study focused on increasing the aqueous solubility of LPSF/GQ-238 by obtaining solid dispersions. Were prepared by the solvent techniques, using Soluplus®, Polyethylene glycol (PEG), and Polyvinylpyrrolidone (PVP-K30) as carriers. Solubility tests, Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), Exploratory Differential Calorimetry (DSC), and Raman Spectroscopy characterized these new intermediate products. The solubility tests showed that the higher the proportion of polymer used in the preparation of the dispersion, the greater the solubility presented. The observation of the morphology by SEM analysis, elucidated, that the new chemical entity (NCE) has a characteristic crystalline structure. The folding of this structure by the polymer was observed in all analyzed dispersions, thus demonstrating the amorphous state of the product. The scales observed in the structures of the dispersions demonstrate the successive wrinkles that occurred. The greater the proportion of the polymer, the greater the number of folds that occurred, which may explain the greater solubility observed in these preparations. The X-ray diffraction profile of the NCE reveals the presence of intense peaks, presenting a crystalline pattern. The polymer, on the other hand, shows amorphous nature, evidenced by the absence of peaks. All the analyzed dispersions did not present the characteristic peaks of the NCE, evidencing the amorphous behavior of the products. The thermal degradation profile of the NCE presents a characteristic crystalline structure endothermic peak. This peak was not observed in any of the obtained dispersions, evidencing the obtaining of a new solid state. Raman spectroscopy showed that peaks in the range 200-400 (cm-1) by NCE were lost when compared to all analyzed dispersions, showing a slight change in the structure of the molecule when dispersed, probably due to the formation of hydrogen bonds with the polymer. The in vitro study showed a significant improvement in the activity of the NCE against the adult worm and to the schistosomulae. It was possible to observe that the obtained solid dispersions were physicochemically and biologically viable for schistosomicidal treatment due to the increase of solubility of the molecule.


Assuntos
Esquistossomose , Esquistossomicidas , Humanos , Tiazolidinas , Esquistossomicidas/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Polímeros/química , Povidona , Difração de Raios X
19.
Int J Biol Macromol ; 231: 123339, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36682648

RESUMO

The Amazon rainforest is considered the largest tropical timber reserve in the world. The management of native forests in the Amazon is one of the most sensitive geopolitical issues today, given its national and international dimension. In this work, we obtained and characterized physicochemical lignins extracted from branches and leaves of Protium puncticulatum and Scleronema micranthum. In addition, we evaluated in vitro its potential as an antioxidant, cytotoxic agent against animal cells and antiparasitic against promastigotes of Leishmania amazonensis, trypomastigotes of T. cruzi and against Plasmodium falciparum parasites sensitive and resistant to chloroquine. The results showed that the lignins obtained are of the GSH type and have higher levels of guaiacyl units. However, they show structural differences as shown by spectroscopic analysis and radar charts. As for biological activities, they showed antioxidant potential and low cytotoxicity against animal cells. Antileishmanial/trypanocidal assays have shown that lignins can inhibit the growth of promastigotes and trypomastigotes in vitro. The lignins in this study showed low anti-Plasmodium falciparum activity against susceptible strains of Plasmodium falciparum and were able to inhibit the growth of the chloroquine-resistant strain. And were not able to inhibit the growth of Schistosoma mansoni parasites. Finally, lignins proved to be promising excipients in the release of benznidazole. These findings show the potential of these lignins not yet studied to promote different biological activities.


Assuntos
Doença de Chagas , Trypanosoma cruzi , Animais , Antiparasitários/uso terapêutico , Lignina/uso terapêutico , Excipientes , Antioxidantes/uso terapêutico , Doença de Chagas/tratamento farmacológico , Cloroquina
20.
J. Health Biol. Sci. (Online) ; 11(1): 1-7, Jan. 2023. tab, ilus
Artigo em Português | LILACS | ID: biblio-1524423

RESUMO

Objetivo: este estudo se propôs a caracterizar o perfil epidemiológico da esporotricose felina no município de São Paulo (SP) no período de 2011 a 2022. Métodos: estudo descritivo dos casos de esporotricose felina registrados entre 2011 e 2022. Foram utilizados dados secundários, provenientes dos bancos de dados da vigilância do município. Resultados: o perfil predominante dos animais é composto por machos, 71,4% (n=2.644), com idade inferior a 4 anos 70,1% (n=1.137) e com livre acesso à rua 51,0% (n=1.348). Foram registrados 811 óbitos, entre os quais foi informado o sexo para 381, sendo estes 77,4% (n=295) machos e 22,6% (n=86) fêmeas. Conclusão: diante dos achados deste estudo, compreende-se que a situação epidemiológica da doença requer ações conjuntas das vigilâncias epidemiológica e ambiental para serem desenvolvidas medidas de prevenção e controle embasadas em uma perspectiva de saúde única.


Objective: this study aimed to characterize the epidemiological profile of feline sporotrichosis in the city of São Paulo (SP) from 2011 to 2022. Methods: this is a descriptive study of feline sporotrichosis cases reported between 2011 and 2022. The data were obtained from a secondary database of the São Paulo Health Surveillance System. Results: the predominant profile of the animals is composed of males 71.4% (n=2,644), under the age of four years old 70.1% (n=1,137), and with free access to streets 51.0% (n=1,348). Furthermore, of the 811 deaths registered, 381 had the gender identified, 77.4% (n=295) were males, and 22.6% (n=86) were females. Conclusion: given the findings of this study, it is understood that the epidemiological situation of the disease requires joint actions by epidemiological and environmental surveillance in order to develop prevention and control measures based on one health perspective.


Assuntos
Animais , Gatos , Esporotricose , Perfil de Saúde , Zoonoses
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