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1.
Microorganisms ; 11(9)2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37764195

ABSTRACT

The spread of nosocomial infections caused by antibiotic-resistant Enterococcus faecalis is one of the major threats to global health at present. While aminoglycosides are often used to combat these infections, their effectiveness is reduced by various resistance mechanisms, including aminoglycoside modifying enzymes, and there are currently no drugs to inhibit these enzymes. To address this issue, this study was conducted to identify potential aminoglycoside adjuvants from a database of 462 flavones. The affinity of these molecules with the nucleotide-binding site (NBS) of aminoglycoside phosphotransferase type IIIa of E. faecalis (EfAPH(3')-IIIa) was evaluated, and the five molecules with the highest binding energies were identified. Of these, four were naphthoflavones, suggesting that their backbone could be useful in designing potential inhibitors. The highest-ranked naphthoflavone, 2-phenyl-4H-benzo[h]chromen-4-one, was modified to generate two new derivatives (ANF2OHC and ANF2OHCC) to interact with the NBS similarly to adenine in ATP. These derivatives showed higher binding free energies, better stability in molecular dynamics analysis and superior pharmacokinetic and toxicological profiles compared to the parent molecule. These findings suggest that these alpha-naphthoflavone derivatives are potential inhibitors of EfAPH(3')-IIIa and that this core may be a promising scaffold for developing adjuvants that restore the sensitivity of aminoglycosides.

2.
J Ethnopharmacol ; 312: 116473, 2023 Aug 10.
Article in English | MEDLINE | ID: mdl-37059251

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Lippia lacunosa Mart. & Schauer is an endemic plant from the Serra do Espinhaço mountain range located on the Atlantic plateau, Brazil. It is known as "chá de pedestre" and "rosmaninho" in folk medicine. This species has a characteristic mango aroma and is widely used by the population for flu, colds, sinus infections, coughing, relaxing baths, and foot baths after long walks. It is often confused with and, therefore, used interchangeably with L. rotundifolia and L. pseudothea. AIM OF THE STUDY: This study aimed to increase scientific knowledge on the ethnopharmacological use of Lippia lacunosa through the evaluation of the micromolecular composition and anti-inflammatory and antinociceptive activities of the hexane and ethanolic extracts, essential oil, and fractions in mice. MATERIALS AND METHODS: The chemical profile of L. lacunosa extracts and fractions were obtained by chromatographic methods such as Ultra-Performance Liquid Chromatography (UPLC), Gas Chromatography (GC), Column Chromatography (CC), and Thin Layer Chromatography (TLC). Carrageenan-induced paw edema was used to investigate the anti-inflammatory activity in mice. Mechanical allodynia induced by carrageenan and hot plate tests were employed to evaluate the antinociceptive activity. RESULTS: The main constituents found in the essential oil were the monoterpenes myrcene (13.81%), linalool (6.84%), ipsenone (21.2%), and myrcenone (25.44%); and sesquiterpenes elemol (7.30%) and spathulenol (3.15%). The chromatograph fractionation of essential oil yielded a fraction rich in the main compounds (F33), ipsenone and mircenone. In experimental models of paw edema and mechanical allodynia induced by carrageenan (600 µg, 30 µL, i.pl.), the administration of hexane extract, essential oil (50 or 100 mg/kg, p.o.) or majority fraction (10 mg/kg, p.o.) reduced paw edema. The ethanolic extract (100 mg/kg) reduced mechanical allodynia only in the 2 nd h of evaluation. On the other hand, the hexane extract (50 or 100 mg/kg) and essential oil (100 mg/kg), as well as the majority fraction (10 mg/kg), reduced mechanical allodynia throughout the evaluation period. The hexane extract, essential oil, and majority fraction F33 also reduced the heat-induced nociceptive response. Also, majority fraction F33 did not affect the time mice spent in the rota-rod apparatus. CONCLUSIONS: The elucidation of the composition of the essential oil and the demonstration of the activity of L. lacunosa in experimental models of acute inflammation and also in models of nociceptive and inflammatory pain can help to increase knowledge on the ancient ethnopharmacological use by the Bandeirantes, aiming at the evaluation of the species as a candidate for herbal medicine or phytopharmaceutical in the treatment of patients with inflammatory and painful conditions.


Subject(s)
Lippia , Oils, Volatile , Mice , Animals , Analgesics/pharmacology , Analgesics/therapeutic use , Analgesics/chemistry , Carrageenan , Lippia/chemistry , Hexanes , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Extracts/chemistry , Hyperalgesia/drug therapy , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/therapeutic use , Oils, Volatile/chemistry , Ethanol/therapeutic use , Edema/chemically induced , Edema/drug therapy
3.
Molecules ; 29(1)2023 Dec 29.
Article in English | MEDLINE | ID: mdl-38202786

ABSTRACT

Increasing rates of bacterial resistance to antibiotics are a growing concern worldwide. The search for potential new antibiotics has included several natural products such as anthraquinones. However, comparatively less attention has been given to anthraquinones that exhibit functional groups that are uncommon in nature. In this work, 114 anthraquinones were evaluated using in silico methods to identify inhibitors of the enzyme phosphopantetheine adenylyltransferase (PPAT) of Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli. Virtual screenings based on molecular docking and the pharmacophore model, molecular dynamics simulations, and free energy calculations pointed to 1,8-dihydroxy-4,5-dinitroanthraquinone (DHDNA) as the most promising inhibitor. In addition, these analyses highlighted the contribution of the nitro group to the affinity of this anthraquinone for the nucleotide-binding site of PPAT. Furthermore, DHDNA was active in vitro towards Gram-positive bacteria with minimum inhibitory concentration (MIC) values of 31.25 µg/mL for S. aureus and 62.5 µg/mL for E. faecalis against both antibiotic-resistant isolates and reference strains but was ineffective against E. coli. Experiments on kill-time kinetics indicated that, at the tested concentrations, DHDNA produced bacteriostatic effects on both Gram-positive bacteria. Overall, our results present DHDNA as a potential PPAT inhibitor, showing antibacterial activity against antibiotic-resistant isolates of S. aureus and E. faecalis, findings that point to nitro groups as key to explaining these results.


Subject(s)
Staphylococcal Infections , Staphylococcus aureus , Humans , Enterococcus faecalis , Escherichia coli , Molecular Docking Simulation , Anthraquinones/pharmacology , Anti-Bacterial Agents/pharmacology
4.
Microorganisms ; 10(12)2022 Dec 08.
Article in English | MEDLINE | ID: mdl-36557686

ABSTRACT

The World Health Organization reported that tuberculosis remains on the list of the top ten threats to public health worldwide. Among the main causes is the limited effectiveness of treatments due to the emergence of resistant strains of Mycobacterium tuberculosis. One of the main drug targets studied to combat M. tuberculosis is DNA gyrase, the only enzyme responsible for regulating DNA topology in this specie and considered essential in all bacteria. In this context, the present work tested the ability of 2824 anthraquinones retrieved from the PubChem database to act as competitive inhibitors through interaction with the ATP-binding pocket of DNA gyrase B of M. tuberculosis. Virtual screening results based on molecular docking identified 7122772 (N-(2-hydroxyethyl)-9,10-dioxoanthracene-2-sulfonamide) as the best-scored ligand. From this anthraquinone, a new derivative was designed harbouring an aminotriazole moiety, which exhibited higher binding energy calculated by molecular docking scoring and free energy calculation from molecular dynamics simulations. In addition, in these last analyses, this ligand showed to be stable in complex with the enzyme and further predictions indicated a low probability of cytotoxic and off-target effects, as well as an acceptable pharmacokinetic profile. Taken together, the presented results show a new synthetically accessible anthraquinone with promising potential to inhibit the GyrB of M. tuberculosis.

5.
Lasers Med Sci ; 37(9): 3379-3392, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36194304

ABSTRACT

This systematic review aimed to answer the research focused question: What are the effects of photobiomodulation (PBM) therapy on bone healing after ionizing irradiation in animal models? The EMBASE, LILACS, LIVIVO, PubMed, Scopus, and Web of Science databases, including gray literature, were searched using the following keywords: "Head and Neck Neoplasms"; "Ionizing Radiation"; "Low-Level Light Therapy"; and "Bone regeneration", focusing on the primary studies that assessed the effects of PBM therapy on animal models of irradiated bone. Six studies have met the eligibility criteria and presented an overall regular quality according to the risk of bias assessment tools. All the studies utilized rat animal model and near-infrared laser PBM at low power output setting. Most of the studies showed increased new bone formation, osteocytes, osteoblasts, and vascularization networking, as a result of PBM therapy. However, only one out of the six studies has not shown any differences in bone healing in both lased and non-lased animal groups. Nevertheless, PBM therapy is a potential tool to improve bone healing induced by ionizing radiation. However, due to the scarce number of studies and the great variability of laser parameters and treatment protocols, a clear conclusion cannot be drawn. Hence, extensive preclinical in vivo studies are warranted to ensure these beneficial effects have been addressed prior to translational clinical trials.


Subject(s)
Head and Neck Neoplasms , Low-Level Light Therapy , Rats , Animals , Low-Level Light Therapy/methods , Bone Regeneration , Wound Healing , Lasers
6.
Exp Parasitol ; 242: 108367, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36055388

ABSTRACT

Gold nanorods (GNRs) are increasingly being studied for diagnostic and therapeutic purposes. Green synthesis based methods with natural compounds as additives stand out as a hope in terms of better synthesis methodology, with advantages of producing potentially less toxic and, perhaps, biologically active GNRs due to influence of natural additives used during synthesis. Exploring green chemistry using different natural phenolic compounds, the present work reveals different in vitro activity of GNRs evaluated against different parasites that causes skin infectious diseases compared to GNRs produced by convencional seed mediated method. This approach brings advantages in producing active GNRs, with ease calling, less cytotoxic and with a better selectivity index (SI) than GNRs synthesized by conventional seed mediated synthesis, opening new possibilities for therapies. Natural compounds used in green syntheses were gallic acid (GA), resveratrol (RSV) and a purified fraction of the hydroalcoholic extract of Stryphnodendron obovatum. GNRs exhibited great activity against Leishmania braziliensis, and the dermatophytes Tricophyton rubrum, T. interdigitale and Microsporum gypseum. The anti-Leishmania and antidermatophytic activity of GNRs reinforce the applicability of GNRs in biomedical field and the influence of synthesis method in biological activity, showing benefits related to the seedless synthesis with natural compounds. In addition, these preliminary results indicate the possibility of exploring at maximum the physical and chemical properties of GNRs in addition to the biological activity itself, such as the development of topical antiparasitic formulations for association with phototherapy.


Subject(s)
Gold , Nanotubes , Gold/chemistry , Resveratrol , Gallic Acid/pharmacology , Antiparasitic Agents
7.
Sci Rep ; 12(1): 4742, 2022 03 18.
Article in English | MEDLINE | ID: mdl-35304513

ABSTRACT

Tuberculosis is a disease that remains a significant threat to public health worldwide, and this is mainly due to the selection of strains increasingly resistant to Mycobacterium tuberculosis, its causative agent. One of the validated targets for the development of new antibiotics is DNA gyrase. This enzyme is a type II topoisomerase responsible for regulating DNA topology and, as it is essential in bacteria. Thus, to contribute to the search for new molecules with potential to act as competitive inhibitors at the active site of M. tuberculosis DNA gyrase B, the present work explored a dataset of 20,098 natural products that were filtered using the FAF-Drugs4 server to obtain a total of 5462 structures that were subsequently used in virtual screenings. The consensus score analysis between LeDock and Auto-Dock Vina software showed that ZINC000040309506 (pyrrolo[1,2-a]quinazoline derivative) exhibit the best binding energy with the enzyme. In addition, its subsequent optimization generated the derivative described as PQPNN, which show better binding energy in docking analysis, more stability in molecular dynamics simulations and improved pharmacokinetic and toxicological profiles, compared to the parent compound. Taken together, the pyrrolo[1,2-a]quinazoline derivative described for the first time in the present work shows promising potential to inhibit DNA gyrase B of M. tuberculosis.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Lymph Node , Antitubercular Agents/chemistry , DNA Gyrase/metabolism , Humans , Molecular Dynamics Simulation , Mycobacterium tuberculosis/metabolism , Quinazolines/metabolism , Quinazolines/pharmacology , Topoisomerase II Inhibitors/metabolism
8.
J Basic Clin Physiol Pharmacol ; 33(4): 499-510, 2021 Jul 19.
Article in English | MEDLINE | ID: mdl-34273917

ABSTRACT

OBJECTIVES: Warfarin is the most widely used anticoagulant in the world, but it has several limitations including its narrow therapeutic range, need for dose adjustment and high potential for interactions. The simultaneous use of other drugs or even medicinal plants and certain foods could interfere with its therapeutic activity. In this context, this study aims to investigate the in vitro anticoagulant potential and phytochemical constitution of 17 plants selected from a previous clinical cross-sectional study (2014), that investigated the habits of plant utilization among patients taking warfarin. METHODS: Ethanol extracts and essential oils were evaluated, in vitro, as to their effect in the prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests. Four species that presented aPTT >50 s were selected for phytochemical evaluation. RESULTS: Thirteen of the 17 plants selected demonstrated a significant anticoagulant effect in at least one of the evaluated parameters. Citrus sinensis (PT=14.75 and aPTT=53.15), Mentha crispa (aPTT=51.25), Mikania laevigata (PT=14.90 and aPTT=52.10), and Nasturtium officinale (aPTT=50.55) showed greater anticoagulant potential compared to normal plasma pool (PT=12.25 and aPTT=37.73). Chemical profiles of these four species were obtained, and certain compounds were identified: rosmarinic acid from M. crispa and isoorientin from N. officinale. CONCLUSIONS: Thus, the results of this study could be a useful indicator for clinical practice towards the possibility of interaction between these plants and anticoagulants, although further clinical research is needed taking into consideration the limitations of in vitro studies. These findings also suggest that further research into the action of these plants could be of real clinical value in identifying potential alternative anticoagulant therapies.


Subject(s)
Plants, Medicinal , Warfarin , Anticoagulants , Cross-Sectional Studies , Prothrombin Time
9.
J Med Primatol ; 50(1): 36-45, 2021 02.
Article in English | MEDLINE | ID: mdl-33219623

ABSTRACT

BACKGROUND: Alouatta spp. are highly susceptible to yellow fever (YF) infection and develop an often fatal disease. The threat posed by an outbreak started in 2016 leads us to investigate vaccination as a potential tool in preventing YF in non-human primates (NHP). METHODS: Susceptible howler monkeys were immunized with three different concentrations of the human Brazilian commercial YF17DD vaccine. Post-vaccination viremia/RNAemia, immunogenicity, and safety were characterized. RESULTS: The vaccine did not produce YF clinical manifestations in any of the NHPs. After immunization, all animals seroconverted demonstrating the ability of the YF vaccine to induce humoral response in Alouatta species. CONCLUSIONS: The present work has demonstrated the safe and immunogenic profile of the existing YF 17DD vaccine in howler monkeys. This knowledge may support further studies with other susceptible monkey species and provide a possible solution for controlling epizootics and preventing the devastation of endangered species.


Subject(s)
Alouatta/immunology , Immunogenicity, Vaccine , Yellow Fever Vaccine/adverse effects , Animals , Female , Male , Species Specificity , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/immunology , Yellow Fever Vaccine/immunology
10.
Methods Mol Biol ; 2116: 139-159, 2020.
Article in English | MEDLINE | ID: mdl-32221920

ABSTRACT

Trypanosoma cruzi is a pathogenic protozoan that still has an impact on public health, despite the decrease in the number of infection cases along the years. T. cruzi possesses an heteroxenic life cycle in which it differentiates in at least four forms. Among the differentiation processes, metacyclogenesis has been exploited in different views by researchers. An intriguing question that rises is how metacyclogenesis is triggered and controlled by cell signaling and which are the differentially expressed proteins and posttranslational modifications involved in this process. An important cell signaling pathway is the protein phosphorylation, and it is reinforced in T. cruzi in which the gene expression control occurs almost exclusively posttranscriptionally. Additionally, the number of protein kinases in T. cruzi is relatively high compared to other organisms. A way to approach these questions is evaluating the cells through phosphoproteomics and proteomics. In this chapter, we will describe the steps from the cell protein extraction, digestion and fractionation, phosphopeptide enrichment, to LC-MS/MS analysis as well as a brief overview on peptide identification. In addition, a published method for in vitro metacyclogenesis will be detailed.


Subject(s)
Phosphoproteins/analysis , Proteomics/methods , Protozoan Proteins/analysis , Trypanosoma cruzi/physiology , Chromatography, Liquid/methods , Gene Expression Regulation, Developmental , Life Cycle Stages/genetics , Parasitology/methods , Phosphoproteins/metabolism , Phosphorylation/physiology , Protozoan Proteins/metabolism , Tandem Mass Spectrometry/methods
11.
Blood Coagul Fibrinolysis ; 31(1): 101-106, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31644450

ABSTRACT

: Evaluate the in-vitro effect of Mentha crispa extract on blood coagulation, compare the conventional coagulometric tests with thrombin generation test (TGT), and study the qualitative micromolecular composition of M. crispa. Extract of M. crispa was incubated with plasma and used in the coagulometric tests: prothrombin and activated partial thromboplastin times, fibrinogen, and TGT. A phytochemical prospection was performed to evaluate the chemical composition of this extract. The extract was efficient in prolonging prothrombin time and activated partial thromboplastin time, and reducing fibrinogen levels and TGT parameters, indicating that the extract of M. crispa inhibited the intrinsic and extrinsic pathways of blood coagulation. The results obtained in TGT are in agreement with the results of conventional coagulometric tests and the in-vitro anticoagulant activity of M. crispa suggests that its use by patients using oral anticoagulants deserves caution.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Tests/methods , Blood Coagulation/drug effects , Mentha/chemistry , Anticoagulants/pharmacology , Healthy Volunteers , Humans
12.
Cell Stress Chaperones ; 24(5): 927-936, 2019 09.
Article in English | MEDLINE | ID: mdl-31368045

ABSTRACT

Phosphorylation is an important event in cell signaling that is modulated by kinases and phosphatases. In Trypanosoma cruzi, the etiological agent of Chagas disease, approximately 2% of the protein-coding genes encode for protein kinases. This parasite has a heteroxenic life cycle with four different development stages. In the midgut of invertebrate vector, epimastigotes differentiate into metacyclic trypomastigotes in a process known as metacyclogenesis. This process can be reproduced in vitro by submitting parasites to nutritional stress (NS). Aiming to contribute to the elucidation of mechanisms that trigger metacyclogenesis, we applied super-SILAC (super-stable isotope labeling by amino acids in cell culture) and LC-MS/MS to analyze different points during NS. This analysis resulted in the identification of 4205 protein groups and 3643 phosphopeptides with the location of 4846 phosphorylation sites. Several phosphosites were considered modulated along NS and are present in proteins associated with various functions, such as fatty acid synthesis and the regulation of protein expression, reinforcing the importance of phosphorylation and signaling events to the parasite. These modulated sites may be triggers of metacyclogenesis.


Subject(s)
Chagas Disease/parasitology , Life Cycle Stages/physiology , Proteome/metabolism , Proteomics/methods , Protozoan Proteins/metabolism , Trypanosoma cruzi/metabolism , Animals , Phosphorylation
13.
Sci Rep ; 8(1): 9754, 2018 06 27.
Article in English | MEDLINE | ID: mdl-29950590

ABSTRACT

Dengue is a mild flu-like arboviral illness caused by dengue virus (DENV) that occurs in tropical and subtropical countries. An increasing number of reports have been indicating that dengue is also associated to neurological manifestations, however, little is known regarding the neuropathogenesis of the disease. Here, using BALB/c mice intravenously infected with DENV-2 strain 66985, we demonstrated that the virus is capable of invading and damaging the host's central nervous system (CNS). Brain and cerebellum of infected animals revealed histological alterations such as the presence of inflammatory infiltrates, thickening of pia matter and disorganization of white matter. Additionally, it was also seen that infection lead to altered morphology of neuroglial cells and apoptotic cell death. Such observations highlighted possible alterations that DENV may promote in the host's CNS during a natural infection, hence, helping us to better understand the neuropathological component of the disease.


Subject(s)
Central Nervous System/pathology , Central Nervous System/virology , Dengue Virus/pathogenicity , Adult , Animals , Brain/pathology , Brain/virology , Cell Line , Cerebellum/pathology , Cerebellum/virology , Disease Models, Animal , Flow Cytometry , Humans , Immunohistochemistry , Male , Mice , Mice, Inbred BALB C
14.
Food Res Int ; 107: 518-527, 2018 05.
Article in English | MEDLINE | ID: mdl-29580515

ABSTRACT

Pineapple (Ananas comosus (L.) Merril) is a tropical fruit rich in nutrients characterized by a pleasant taste and widely consumed in several countries. It is used to produce juice, jams and wine. In this work, 150 yeasts isolates were obtained from peel (18) and spontaneously fermented pineapple pulp (132). The probiotic potential of 50 isolates was studied. Survival at pH 2.0, pepsin 3.0 g/L, and tolerance of bile salts (0.1 and 1% (w/v) were determined as indicators of survival potential of the isolates during the passage through the human gastrointestinal tract in simulated conditions. The selected isolates were also evaluated for their resistance to 6 antibiotics, antimicrobial activity against 6 pathogenic bacteria and autoaggregation and hydrophobicity properties. Five of them survived to gastrointestinal conditions, showed antibiotic resistance and autoaggregation properties. They were identified by MALDI-TOF MS and sequencing of ITS region as Candida lusitaniae (3) and Meyerozyma caribbica (2). Among these isolates, M. caribbica 9 D was evaluated in the production of a fermented pineapple beverage. The Saccharomyces cerevisiae var. boulardii was used as control, due to the fact that it is the only commercially available probiotic yeast. With M. caribbica inoculum, the beverage produced showed higher concentrations of residual glucose (24.19 g/L) and fructose (8.67 g/L), lower concentration of acetic acid (0.22 g/L); higher total phenolic compounds (196.93 mg/L), catechin (155.56 mg/L), chlorogenic acid (3.64 mg/L), vanillin (0.18 mg/L) and ferulic acid (33.2 mg/L). It was observed that M. caribbica population remained stable during refrigerated storage with cell counts greater than 7.00 log CFU/mL over 21 days. Compared to beverage produced with S. cerevisiae var. boulardii, the one produced with M. caribbica presented greater acceptance in the sensorial analysis for taste, aroma and general acceptance. The fermented pineapple beverage prepared with M. caribbica proved to be a good alternative in development of a potential probiotic beverage with different sensory and nutritional properties.


Subject(s)
Ananas/chemistry , Beverages/analysis , Fermentation , Functional Food/analysis , Probiotics/analysis , Yeasts/chemistry , Probiotics/chemistry
15.
Sci Rep ; 7(1): 9899, 2017 08 29.
Article in English | MEDLINE | ID: mdl-28852088

ABSTRACT

Trypanosoma cruzi metacyclogenesis is a natural process that occurs inside the triatomine vector and corresponds to the differentiation of non-infective epimastigotes into infective metacyclic trypomastigotes. The biochemical alterations necessary for the differentiation process have been widely studied with a focus on adhesion and nutritional stress. Here, using a mass spectrometry approach, a large-scale phospho(proteome) study was performed with the aim of understanding the metacyclogenesis processes in a quantitative manner. The results indicate that major modulations in the phospho(proteome) occur under nutritional stress and after 12 and 24 h of adhesion. Significant changes involve key cellular processes, such as translation, oxidative stress, and the metabolism of macromolecules, including proteins, lipids, and carbohydrates. Analysis of the signalling triggered by kinases and phosphatases from 7,336 identified phosphorylation sites demonstrates that 260 of these sites are modulated throughout the differentiation process, and some of these modulated proteins have previously been identified as drug targets in trypanosomiasis treatment. To the best of our knowledge, this study provides the first quantitative results highlighting the modulation of phosphorylation sites during metacyclogenesis and the greater coverage of the proteome to the parasite during this process. The data are available via ProteomeXchange with identifier number PXD006171.


Subject(s)
Phosphoproteins/metabolism , Proteome , Protozoan Proteins/metabolism , Trypanosoma cruzi/physiology , Cytoskeleton/metabolism , Life Cycle Stages , Phosphoproteins/chemistry , Protein Biosynthesis , Protozoan Proteins/chemistry
16.
Biomed Res Int ; 2017: 9840210, 2017.
Article in English | MEDLINE | ID: mdl-28798938

ABSTRACT

Leishmaniasis remains a serious public health problem in developing countries without effective control, whether by vaccination or chemotherapy. Part of the failure of leishmaniasis control is due to the lack of new less toxic and more effective drugs able to eliminate both the lesions and the parasite. Oxiranes derived from naphthoquinones now being assayed are promising drugs for the treatment of this group of diseases. The predicted pharmacokinetic properties and toxicological profiles of epoxy-α-lapachone and epoxymethoxy-lawsone have now been compared to those of meglumine antimoniate, and histological changes induced by these drugs in noninfected BALB/c mice tissues are described. Effects of these compounds on liver, kidney, lung, heart, and cerebral tissues of healthy mice were examined. The data presented show that both these oxiranes and meglumine antimoniate induce changes in all BALB/c mice tissues, with the lung, heart, and brain being the most affected. Epoxymethoxy-lawsone was the most toxic to lung tissue, while most severe damage was caused in the heart by epoxy-α-lapachone. Meglumine antimoniate caused mild-to-moderate changes in heart and lung tissues.


Subject(s)
Epoxy Compounds/adverse effects , Leishmaniasis/drug therapy , Meglumine/adverse effects , Organometallic Compounds/adverse effects , Animals , Epoxy Compounds/pharmacology , Meglumine/pharmacology , Meglumine Antimoniate , Mice , Mice, Inbred BALB C , Organ Specificity , Organometallic Compounds/pharmacology
17.
Rev. baiana saúde pública ; 41(3): 759-773, jul. 2017.
Article in Portuguese | LILACS, CONASS, SES-BA | ID: biblio-906446

ABSTRACT

A identidade trans está relacionada ao reconhecimento da identidade de gênero oposta ao sexo biológico. Essa característica faz com que essa população sofra diversos preconceitos e se torne vulnerável. Em nível programático, esse processo, quando ocorre nas unidades de saúde, faz com que as necessidades em saúde das travestis não sejam reconhecidas pelos profissionais da Atenção Primária. O presente trabalho tem como objeto de estudo as necessidades em saúde das travestis e objetivou discutir o atendimento das suas necessidades nos serviços de saúde da Atenção Primária. Trata-se de uma pesquisa de abordagem qualitativa do tipo descritiva. A coleta de dados ocorreu nos meses de abril e maio de 2013, quando foram realizadas entrevistas semiestruturadas com cinco travestis. A análise da entrevista foi realizada por meio da técnica de análise de conteúdo. Diante das falas das participantes emergiram três categorias temáticas: o conceito de saúde para travestis, a construção do corpo das travestis e o atendimento das travestis nas Unidades Básicas de Saúde. Foram identificadas como necessidades em saúde específicas: o acolhimento no serviço de saúde com a utilização do nome social da travesti, de modo a evitar a discriminação e constrangimentos na sala de espera; atendimento especializado por profissionais de saúde capacitados; proteção contra a violência desencadeada, principalmente em função da discriminação; orientações quanto à utilização de hormônios femininos; oferta de testes rápidos em toda Atenção Básica para diagnóstico de HIV, Hepatite B/C e Sífilis.


Trans identity is related to the recognition of gender identity as opposed to biological sex. This characteristic causes this population to suffer diverse prejudices and become vulnerable. At the programmatic level, this process, when it occurs in health facilities, makes the health needs of transvestites not to be recognized by Primary Care professionals. The objective of the present study is to study the health needs of the transvestites and aimed to discuss the meeting of their needs in Primary Health Care services. It is a qualitative research of descriptive type. Data collection took place in April and May 2013, when semi-structured interviews were carried out with five transvestites. The analysis of the interviews was performed by means of the technique of content analysis. Three themes emerged from the participants' speeches: the concept of health for transvestites, the construction of the body of transvestites and the treatment of transvestites in Basic Health Units. Specific health needs were identified: the reception in the health service using the social name of the transvestite, in order to avoid discrimination and constraints in the waiting room; specialized care by trained health professionals; protection against violence, mainly due to discrimination; guidelines on the use of female hormones; offer rapid testing throughout Basic Care for the diagnosis of HIV, Hepatitis B / C and Syphilis.


La identidad trans está relacionada al reconocimiento de la identidad de género opuesta al sexo biológico. Esta característica hace que esta población sufra diversos prejuicios y vuelvase vulnerable. A nivel programático, ese proceso, cuando ocurre en las unidades de salud, hace que las necesidades en salud de las travestis no sean reconocidas por los profesionales de la Atención Primaria. El presente trabajo tiene como objeto de estudio las necesidades en salud de las travestis y objetivó discutir la atención de sus necesidades en los servicios de salud de la Primaria Atención. Tratase de una investigación de abordaje cualitativo de tipo descriptivo. La recolección de datos ocurrió en los meses de abril y mayo de 2013, cuando se realizaron entrevistas semiestructuradas con cinco travestis. El análisis de la entrevista fue realizado por medio de la técnica del análisis de contenido. Ante las declaraciones de las participantes surgieron tres categorías temáticas: el concepto de salud para travestis, la construcción del cuerpo de las travestis y la atención a las travestis en las Unidades Básicas de Salud. Fueron identificadas como necesidades en salud específicas: la acogida en el servicio de salud con la utilización del nombre social de la travesti, para evitar la discriminación y las constreñimiento en la sala de espera; atención especializada por profesionales de la salud capacitados; protección contra la violencia desencadenada, principalmente en función de la discriminación; orientaciones sobre la utilización de hormonas femeninas; oferta de pruebas rápidas en toda Atención Básica para diagnóstico de VIH, Hepatitis B / C y Sífilis.


Subject(s)
Humans , Primary Health Care , Transvestism , Gender Identity
18.
Nosso clínico ; 20(117): 44-48, mai-jun. 2017. ilus
Article in Portuguese | VETINDEX | ID: biblio-1485987

ABSTRACT

Um hamster (Mesocrícetusauratus), de sexo feminino, com 68g e 3 anos, foi atendido no HOVET apresentando secreção mucosanguinolenta fétida em vagina, vômitos esporádicos e não urinava há dias. Na palpação abdominal notou-se a existência de uma massa abdominal. Foi realizado raios-X e observouse a massa na região uterina. O tratamento indicado foi a laparotomia exploratória e retirada do tumor. No preparo pré-operatório foi medicado com enrofloxacina (15 mg/kg, 1M), cloridrato de tramadol (2 mg/kg), 1M e cetoprofeno (2 mg/kg 1M). Para a indução foi utilizado máscara com isofluorano 3% e na manutenção anestésica foi utilizada máscara com isofluoranos 1,5%. O paciente não apresentou complicações pósoperatórias, e sua condição clínica manteve-se estável. O resultado da histopatologia apontou a presença de leiomiossarcoma, o animal foi encaminhado para procedimento cirúrgico com retirada total do tumor. A remoção dos pontos cirúrgicos se deu 10 dias após o procedimento cirúrgico.


A hamster (Mesocricetusauratus), females, with 68g and 3, was treated at HOVET featuring mucosanguinolenta fetid secretion in the vagina, sporadic vomiting and not urinated for days. In abdominal palpation noted the existence of an abdominal mass. X-ray was performed and the mass was observed in the uterine region. The recommended treatment was to exploratory laparotomy and tumor removal. Preoperative preparation was treated with enrofloxacin (15 mg/kg, 1M), tramadol hydrochloride (2 mg/kg), and 1M Ketoprofen (2 mg/kg 1M). For induction, was used masks with isoflurane 3% and maintenance of anesthesia was used masks with isofluoranos 1.5%. The patient had no postoperative complications, and their condition was stable. The result of the histopathology showed the presence of leiomyosarcoma the animal was taken to surgery with complete removal of the tumor. The removal of stitches took ten days after the surgical procedure.


Un hámster (Mesocricetusauratus), hembras, con 68g y 3, se trató a Hovet que incluyen secreción fétida mucosanguinolenta en la vagina, vómitos esporádicos y no orinaba durante días. En la palpación abdominal se senaló la existencia de una masa abdominal. De rayos X se realizó y se observó la masa en la región uterina. El tratamiento recomendado era de laparotomía exploratoria y extirpación de tumores. La preparación preoperatoria se trató con enrofloxacina (15 mg/kg, 1M), clorhidrato de tramado I (2 mg/kg), y la mensajería instantánea Ketoprofeno (2 mg/kg 1M). Para la inducción se utilizó máscaras con isoflurano 3% y el mantenimiento de la anestesia fue utilizado máscaras con isofluoranos 1,5%. El paciente no tuvo complicaciones postoperatorias, y su condición era estable. El resultado de la histopatología mostró la presencia de leiomiosarcoma el animal fue llevado a cirugía con eliminación completa del tumor. El retiro de puntos llevó diez días después de la intervención quirúrgica.


Subject(s)
Female , Animals , Cricetinae/physiology , Leiomyosarcoma/veterinary , Uterus/pathology , Neoplasms/veterinary , Medical Oncology , Surgical Procedures, Operative/veterinary
19.
Nosso Clín. ; 20(117): 44-48, mai-jun. 2017. ilus
Article in Portuguese | VETINDEX | ID: vti-690809

ABSTRACT

Um hamster (Mesocrícetusauratus), de sexo feminino, com 68g e 3 anos, foi atendido no HOVET apresentando secreção mucosanguinolenta fétida em vagina, vômitos esporádicos e não urinava há dias. Na palpação abdominal notou-se a existência de uma massa abdominal. Foi realizado raios-X e observouse a massa na região uterina. O tratamento indicado foi a laparotomia exploratória e retirada do tumor. No preparo pré-operatório foi medicado com enrofloxacina (15 mg/kg, 1M), cloridrato de tramadol (2 mg/kg), 1M e cetoprofeno (2 mg/kg 1M). Para a indução foi utilizado máscara com isofluorano 3% e na manutenção anestésica foi utilizada máscara com isofluoranos 1,5%. O paciente não apresentou complicações pósoperatórias, e sua condição clínica manteve-se estável. O resultado da histopatologia apontou a presença de leiomiossarcoma, o animal foi encaminhado para procedimento cirúrgico com retirada total do tumor. A remoção dos pontos cirúrgicos se deu 10 dias após o procedimento cirúrgico.(AU)


A hamster (Mesocricetusauratus), females, with 68g and 3, was treated at HOVET featuring mucosanguinolenta fetid secretion in the vagina, sporadic vomiting and not urinated for days. In abdominal palpation noted the existence of an abdominal mass. X-ray was performed and the mass was observed in the uterine region. The recommended treatment was to exploratory laparotomy and tumor removal. Preoperative preparation was treated with enrofloxacin (15 mg/kg, 1M), tramadol hydrochloride (2 mg/kg), and 1M Ketoprofen (2 mg/kg 1M). For induction, was used masks with isoflurane 3% and maintenance of anesthesia was used masks with isofluoranos 1.5%. The patient had no postoperative complications, and their condition was stable. The result of the histopathology showed the presence of leiomyosarcoma the animal was taken to surgery with complete removal of the tumor. The removal of stitches took ten days after the surgical procedure.(AU)


Un hámster (Mesocricetusauratus), hembras, con 68g y 3, se trató a Hovet que incluyen secreción fétida mucosanguinolenta en la vagina, vómitos esporádicos y no orinaba durante días. En la palpación abdominal se senaló la existencia de una masa abdominal. De rayos X se realizó y se observó la masa en la región uterina. El tratamiento recomendado era de laparotomía exploratoria y extirpación de tumores. La preparación preoperatoria se trató con enrofloxacina (15 mg/kg, 1M), clorhidrato de tramado I (2 mg/kg), y la mensajería instantánea Ketoprofeno (2 mg/kg 1M). Para la inducción se utilizó máscaras con isoflurano 3% y el mantenimiento de la anestesia fue utilizado máscaras con isofluoranos 1,5%. El paciente no tuvo complicaciones postoperatorias, y su condición era estable. El resultado de la histopatología mostró la presencia de leiomiosarcoma el animal fue llevado a cirugía con eliminación completa del tumor. El retiro de puntos llevó diez días después de la intervención quirúrgica.


Subject(s)
Animals , Female , Leiomyosarcoma/veterinary , Uterus/pathology , Cricetinae/physiology , Surgical Procedures, Operative/veterinary , Medical Oncology , Neoplasms/veterinary
20.
Int J Biol Macromol ; 92: 1040-1048, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27514442

ABSTRACT

In vitro effects of acetylated pectin (OP) isolated from cacao pod husks (Theobroma cacao L.), its partially deacetylated and de-esterified form (MOP), and a commercial homogalacturonan (PG) were investigated on murine peritoneal macrophages. MOP stood out among the studied pectins. After 48h of incubation, compared with the control group, it was able to promote significant macrophage morphological differentiation from resident to activated stage and also stimulated nitric oxide production, which reached a level of 85% of that of LPS stimulus. In the presence of the highest tested concentration of MOP (200µg·mL-1), the levels of the cytokines TNF-α (6h) and IL-12 and IL-10 (48h) increased substantially in relation to untreated cells. Our results show that the partial deacetylation and de-esterification of pectin extracted from cacao pod husks (T. cacao L.) produced a polymer with greater ability than its native form to activate macrophages to a cytotoxic phenotype. Like this, they provide the possibility of a therapeutic application to MOP, which could lead to a decreased susceptibility to microbial infection besides antitumor activity. Additionally, the present results also corroborate with the proposition of that the chemical modifications of the biopolymers can result in an improved molecule with new possibilities of application.


Subject(s)
Cacao/chemistry , Macrophage Activation/drug effects , Macrophages, Peritoneal/drug effects , Pectins/pharmacology , Acetylation , Animals , Female , Gene Expression , Inflammation , Interleukin-10/genetics , Interleukin-10/immunology , Interleukin-12/genetics , Interleukin-12/immunology , Lipopolysaccharides/pharmacology , Macrophages, Peritoneal/cytology , Macrophages, Peritoneal/immunology , Mice , Nitric Oxide/agonists , Nitric Oxide/biosynthesis , Pectins/chemistry , Pectins/isolation & purification , Primary Cell Culture , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
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