RESUMO
In the pursuit of novel antioxidant therapies for the prevention and treatment of neurodegenerative diseases, three new arylpiperazine derivatives (LQFM181, LQFM276, and LQFM277) were synthesized through a molecular hybridization approach involving piribedil and butylated hydroxytoluene lead compounds. To evaluate the antioxidant and neuroprotective activities of the arylpiperazine derivatives, we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (neurotoxicity induced by 3-nitropropionic acid in Swiss mice) models. In the in vitro tests, LQFM181 showed the most promising antioxidant activity at the neuronal membrane and cytoplasmic levels, and significant neuroprotective activity against the neurotoxicity induced by 3-nitropropionic acid. Hence, this compound was further subjected to in vivo evaluation, which demonstrated remarkable antioxidant capacity such as reduction of MDA and carbonyl protein levels, increased activities of succinate dehydrogenase, catalase, and superoxide dismutase. Interestingly, using the same in vivo model, LQFM181 also reduced locomotor behavior and memory dysfunction through its ability to decrease cholinesterase activity. Consequently, LQFM181 emerges as a promising candidate for further investigation into its neuroprotective potential, positioning it as a new therapeutic agent for neuroprotection.
Assuntos
Antioxidantes , Fármacos Neuroprotetores , Nitrocompostos , Piperazinas , Propionatos , Animais , Propionatos/toxicidade , Nitrocompostos/toxicidade , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Camundongos , Piperazinas/farmacologia , Piperazinas/química , Humanos , Linhagem Celular Tumoral , Antioxidantes/farmacologia , Masculino , Succinato Desidrogenase/metabolismo , Superóxido Dismutase/metabolismo , Catalase/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacosRESUMO
Background: Vaccination is an extremely safe public health intervention, but rare IgE-mediated adverse events must be identified to avoid the risk of anaphylaxis in the event of reexposure. However, using only clinical history to diagnose previous allergic reactions may lead to overdiagnosis of vaccine allergy and even to the use of medical exemptions as a subterfuge to mandatory vaccination. Methods: We conducted a retrospective study to describe the outcomes of patients with a history of vaccine or vaccine component allergy who were evaluated at our unit from 2011 to 2017. Data on allergy history, skin test results, vaccines prescribed, and adverse events were retrieved from the medical records at the Centro de Referência para Imunobiológicos Especiais (Reference Center of Special Immunobiologicals)-Fiocruz, in Rio de Janeiro, Brazil. Results: Of 34 adults with history of allergy to vaccine or vaccine components, 32 (94.1%) were successfully vaccinated without serious adverse events after our evaluation. In 12 patients (35%), the time elapsed between the allergy symptoms and evaluation in the Centro de Referência para Imunobiológicos Especiais-Fiocruz was more than 10 years. Conclusion: Specialized care and use of skin tests allowed safe vaccination of the majority of patients. An objective, systematic evaluation of a history of vaccine allergy can prevent its improper use to avoid mandatory vaccination and reduce missed opportunities for immunization.
RESUMO
Casearia species are found in the America, Africa, Asia, and Australia and present pharmacological activities, besides their traditional uses. Here, we reviewed the chemical composition, content, pharmacological activities, and toxicity of the essential oils (EOs) from Casearia species. The EO physical parameters and leaf botanical characteristics were also described. The bioactivities of the EOs from the leaves and their components include cytotoxicity, anti-inflammatory, antiulcer, antimicrobial, antidiabetic, antioxidant, antifungal, and antiviral activities. The main components associated with these activities are the α-zingiberene, (E)-caryophyllene, germacrene D, bicyclogermacrene, spathulenol, α-humulene, ß-acoradiene, and δ-cadinene. Data on the toxicity of these EOs are scarce in the literature. Casearia sylvestris Sw. is the most studied species, presenting more significant pharmacological potential. The chemical variability of EOs components was also investigated for this species. Caseria EOs have relevant pharmacological potential and must be further investigated and exploited.
Assuntos
Anti-Infecciosos , Casearia , Óleos Voláteis , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Casearia/química , Extratos Vegetais/química , Antifúngicos/farmacologiaRESUMO
Varronia curassavica displays anti-inflammatory, antiulcerogenic, and antioxidant activities. Herein, we employed new UHPLC -UV green chromatographic methods for the analysis of inâ
vitro antioxidant and anti-inflammatory activities of V. curassavica and its embryotoxicity in Zebrafish. Cordialin A, brickellin, and artemetin were purified from the ethanol (EtOH) extract of V. Curassavica leaves and identified using spectrometric techniques. In line with Green Analytical Chemistry principles, the proposed UHPLC methods involve the use of ethanol as organic modifier with low mobile phase consumption, and without sample pretreatment (OLE-UHPLC-UV). The application of the Agree and HPLC-EAT tools for greenness assessment yielded this pattern: HPLC-UV (reference)Assuntos
Antioxidantes
, Extratos Vegetais
, Animais
, Extratos Vegetais/química
, Antioxidantes/química
, Peixe-Zebra
, Anti-Inflamatórios/farmacologia
, Folhas de Planta/química
, Etanol
RESUMO
LQFM018 is a novel antineoplastic prototype, showing an expressive drug-triggered K562 leukemic cells death mechanism, through necroptotic signaling. Due to its promising effect, this study aimed to evaluate the pharmacokinetics of LQFM018 in rats, using a new validated bioanalytical LC-MS/MS-based method. Chromatographic column was an ACE® C18 (100 mm × 4.6 mm, 5 µm) eluted by a mobile phase composed of ammonium acetate 2 mM and formic acid 0.025%:methanol (50:50, v/v), under flow of 1.2 mL/min and injection volume of 3.0 µL. LQFM018 was extracted from rat plasma by a simple liquid-liquid method, using MTBE solvent. Rats were administered intraperitoneally at LQFM018 100 mg/kg dose and blood samples were collect at times of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9 h. Bioanalytical-LC-MS/MS-based method was rapid, high throughput and sensitive with a good linearity ranging from 10 (LLOQ) to 15000 ng/mL, besides precise and accurate, ranging of 0.8-7.3% and 96.8-107.6%, respectively. The prototype LQFM018 was rapid and well absorbed, and highly distributed, apparently due to its high lipid solubility. These features are primordial for an anticancer agent in the treatment of deep tumors, such as bone marrow neoplasms, in which the drug might permeate easily tissue barriers. Also, LQFM018 has demonstrated a high clearance, according to a low t1/2in rats, indicating a relative fast elimination phase related to a possible intense hepatic biotransformation. These information support further studies to establish new understands on pharmacokinetics of promising antineoplastic prototype LQFM018 from preclinical and clinical evaluations.
Assuntos
Antineoplásicos , Espectrometria de Massas em Tandem , Ratos , Animais , Cromatografia Líquida/métodos , Piperazina , Espectrometria de Massas em Tandem/métodos , Piperazinas , Reprodutibilidade dos TestesRESUMO
Oral preparations of Casearia sylvestris (guacatonga) are used as antacid, analgesic, anti-inflammatory, and antiulcerogenic medicines. The clerodane diterpenes casearin B and caseargrewiin F are major active compounds in vitro and in vivo. The oral bioavailability and metabolism of casearin B and caseargrewiin F were not previously investigated. We aimed to assess the stability of casearin B and caseargrewiin F in physiological conditions and their metabolism in human liver microsomes. The compounds were identified by UHPLC-QTOF-MS/MS and quantified by validated LC-MS methods. The stability of casearin B and caseargrewiin F in physiological conditions was assessed in vitro. Both diterpenes showed a fast degradation (p < 0.05) in simulated gastric fluid. Their metabolism was not mediated by cytochrome P-450 enzymes, but the depletion was inhibited by the esterase inhibitor NaF. Both diterpenes and their dialdehydes showed a octanol/water partition coefficient in the range of 3.6 to 4.0, suggesting high permeability. Metabolism kinetic data were fitted to the Michaelis-Menten profile with KM values of 61.4 and 66.4 µM and Vmax values of 327 and 648 nmol/min/mg of protein for casearin B and caseargrewiin F, respectively. Metabolism parameters in human liver microsomes were extrapolated to predict human hepatic clearance, and suggest that caseargrewiin F and casearin B have a high hepatic extraction ratio. In conclusion, our data suggest that caseargrewiin F and casearin B present low oral bioavailability due to extensive gastric degradation and high hepatic extraction.
Assuntos
Diterpenos Clerodânicos , Humanos , Diterpenos Clerodânicos/química , Espectrometria de Massas em Tandem , Fígado , Microssomos HepáticosRESUMO
Molecular modification of compounds remains important strategy towards the discovery of new drugs. In this sense, this study presents a new pyrazole derivative 5-(1-(2-fluorophenyl)-1H-pyrazol-4-yl)-1H-tetrazole (LQFM039) and evaluated the anti-inflammatory, analgesic, and vasorelaxant effects of this compound as well the mechanisms of action involved in the pharmacological effects. For this, mice were orally treated with LQFM039 (17.5, 35, or 70 mg/kg) prior acetic acid-induced abdominal writhing, formalin, tail flick, and carrageenan-induced paw edema protocols. In addition, vascular reactivity protocols were made with aortic rings contraction with phenylephrine and stimulated with graded concentrations of LQFM039. Abdominal writhing and licking time in both neurogenic and inflammatory phases of formalin were reduced with LQFM039 without altering latency to nociceptive response in the tail flick test. Carrageenan-induced paw edema showed that LQFM039 reduces edema and cell migration. In addition, the mechanism of action of LQFM039 involves NO/cGMP pathway and calcium channels, since this new pyrazole derivate elicited concentration-dependent relaxation attenuated by Nω-nitro-l-arginine methyl ester and 1H-[1,2,4] oxadiazolo [4,3-alpha]quinoxalin-1-one, and blockade of CaCl2-induced contraction. Altogether, our finding suggests anti-inflammatory, antinociceptive, and vasorelaxant effect of this new pyrazole derivative with involvement of NO/cGMP pathway and calcium channels.
Assuntos
Analgésicos , Vasodilatadores , Camundongos , Animais , Analgésicos/farmacologia , Canais de Cálcio/efeitos adversos , Canais de Cálcio/metabolismo , Carragenina/efeitos adversos , Anti-Inflamatórios/farmacologia , Pirazóis/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Anti-Inflamatórios não Esteroides/efeitos adversos , FormaldeídoRESUMO
The objectives were to estimate hepatitis A virus seroprevalence in subjects attending to a travel medicine and immunization clinic in Rio de Janeiro, Brazil, and to develop a prediction model for hepatitis A virus seroprevalence. This retrospective research included individuals sequentially from April 2011 to June 2019 at a travel medicine and special population immunization clinic with an anti-hepatitis A virus IgG chemiluminescence result. Participants' data were verified via electronic medical records. Data were split into development and validation set taking 2018 as the date break. A cross-validated elastic generalized linear model with binomial distribution was performed. In total, 2,944 subjects were analyzed. Hepatitis A virus overall seroprevalence was 67.8%. Health professionals, travelers, and those who had contact with immunocompromised subjects had lower seroprevalence (40%-55%), whereas subjects with chronic conditions (heart, lung, and liver) ranged from 89% to 94%. The retained predictors in the final model were sex, age, year of birth, travelers, HIV/AIDS, spleen dysfunction, transplant candidates, household communicators, cancer-related immunosuppression, health care professionals. Area under the curve was 0.836 and maximum error was 0.051. Users can make predictions with the following calculator: https://pedrobrasil.shinyapps.io/INDWELL/. The groups with lower seroprevalence should be evaluated more carefully regarding need for hepatitis A virus vaccination even when they seek immunization clinics for other purposes.
Assuntos
Síndrome da Imunodeficiência Adquirida , Gravidez , Feminino , Humanos , Estudos Soroepidemiológicos , Brasil/epidemiologia , Estudos Retrospectivos , PartoRESUMO
BACKGROUND: L-proline transporter (PROT/SLC6A7) is closely associated with glutamatergic neurotransmission, where L-proline modulates the NMDA receptor (NMDAR) function. NMDAR-mediated excitotoxicity is a primary cause of neuronal death following stroke, which is triggered by the uncontrolled release of glutamate during the ischemic process. After ischemic stroke, L-proline levels show a reduction in the plasma, but high circulating levels of this molecule indicate good functional recovery. This work aimed to produce new PROT inhibitors and explore their effects on ischemic stroke. METHODS: Initially, we built a three-dimensional model of the PROT protein and run a molecular docking with the newly designed compounds (LQFM215, LQFM216, and LQFM217). Then, we synthesized new PROT inhibitors by molecular hybridization, and proline uptake was measured in ex vivo and in vivo models. The behavioral characterization of the treated mice was performed by the open-field test, elevated plus-maze, Y-maze, and forced swimming test. We used the permanent middle cerebral artery occlusion (MCAO) model to study the ischemic stroke damage and analyzed the motor impairment with limb clasping or cylinder tests. RESULTS: LQFM215 inhibited proline uptake in hippocampal synaptosomes, and the LQFM215 treatment reduced proline levels in the mouse hippocampus. LQFM215 reduced the locomotor and exploratory activity in mice and did not show any anxiety-related or working memory impairments. In the MCAO model, LQFM215 pre-treatment and treatment reduced the infarcted area and reduced motor impairments in the cylinder test and limb clasping. CONCLUSIONS: This dataset suggests that the new compounds inhibit cerebral L-proline uptake and that LQFM215 promotes neuroprotection and neuro-repair in the acute ischemic stroke model.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Camundongos , Animais , AVC Isquêmico/complicações , Neuroproteção , Simulação de Acoplamento Molecular , Infarto da Artéria Cerebral Média/complicações , Receptores de N-Metil-D-Aspartato , Prolina/farmacologia , Isquemia Encefálica/complicações , Modelos Animais de DoençasRESUMO
The objectives were to estimate hepatitis A virus seroprevalence in subjects attending to a travel medicine and immunization clinic in Rio de Janeiro, Brazil, and to develop a prediction model for hepatitis A virus seroprevalence. This retrospective research included individuals sequentially from April 2011 to June 2019 at a travel medicine and special population immunization clinic with an anti-hepatitis A virus IgG chemiluminescence result. Participants' data were verified via electronic medical records. Data were split into development and validation set taking 2018 as the date break. A cross-validated elastic generalized linear model with binomial distribution was performed. In total, 2,944 subjects were analyzed. Hepatitis A virus overall seroprevalence was 67.8%. Health professionals, travelers, and those who had contact with immunocompromised subjects had lower seroprevalence (40%-55%), whereas subjects with chronic conditions (heart, lung, and liver) ranged from 89% to 94%. The retained predictors in the final model were sex, age, year of birth, travelers, HIV/AIDS, spleen dysfunction, transplant candidates, household communicators, cancer-related immunosuppression, health care professionals. Area under the curve was 0.836 and maximum error was 0.051. Users can make predictions with the following calculator: https://pedrobrasil.shinyapps.io/INDWELL/. The groups with lower seroprevalence should be evaluated more carefully regarding need for hepatitis A virus vaccination even when they seek immunization clinics for other purposes.
Este estudo teve como objetivo estimar a soroprevalência do vírus da hepatite A, em indivíduos atendidos em uma clínica de medicina de viagem e imunização no Rio de Janeiro, Brasil, e desenvolver um modelo de predição para a soroprevalência do vírus da hepatite A. Esta pesquisa retrospectiva incluiu indivíduos sequencialmente de abril de 2011 a junho de 2019, em uma clínica de medicina de viagem e uma clínica de vacinação de população especial, que, por qualquer motivo, tem um resultado de quimioluminescência IgG antivírus da hepatite A . Os dados dos participantes foram verificados em prontuário eletrônico. Os dados foram divididos em desenvolvimento e validação, tomando 2018 como data limite da divisão. Um modelo linear generalizado elástico com distribuição binomial submetido a validação cruzada foi aplicado. Foram analisados 2.944 indivíduos atendidos. A soroprevalência geral do vírus da hepatite A foi de 67,8%. Profissionais de saúde, viajantes e contatantes de indivíduos imunocomprometidos apresentaram menor soroprevalência, variando de 40% a 55%, enquanto indivíduos com condições crônicas (coração, pulmão e fígado) tiveram soroprevalência variando de 89% a 94%. Os preditores retidos no modelo final foram sexo, idade, ano de nascimento, viajantes, HIV/aids, asplenia funcional, candidatos a transplante, comunicante domiciliar, imunossupressão relacionada ao câncer e profissionais de saúde. A área sob a curva foi de 0,836 e o erro máximo foi de 0,051. Os usuários podem fazer previsões com uma calculadora (https://pedrobrasil.shinyapps.io/INDWELL/). Os grupos com menor soroprevalência devem ser avaliados com mais cuidado quanto à necessidade de vacinação contra o vírus da hepatite A, mesmo quando procuram clínicas de vacinação para outros fins.
Los objetivos del estudio son estimar la seroprevalencia de hepatitis A en sujetos que asisten a una clínica de medicina para viajeros e inmunización en Río de Janeiro, Brasil, y desarrollar un modelo de predicción de la seroprevalencia de hepatitis A. Esta investigación de seguimiento retrospectivo incluyó a individuos de forma secuencial desde abril de 2011 hasta junio de 2019 en una clínica de medicina para viajeros y de vacunación de poblaciones especiales que por cualquier motivo tienen un resultado de quimioluminiscencia IgG anti-hepatitis A. Los datos de los participantes se verificaron en los registros médicos electrónicos. Los datos se dividieron en conjunto de desarrollo y validación tomando 2018 como fecha de corte. Se realizó un modelo lineal generalizado validado cruzado elástico con distribución binomial. Se analizaron un total de 2.944 sujetos atendidos. La seroprevalencia global del hepatitis A fue del 67,8%. Los profesionales sanitarios, los viajeros y las personas en contacto con sujetos inmunodeprimidos presentaron una seroprevalencia más baja, que osciló entre el 40% y el 55%, mientras que los sujetos con afecciones crónicas (cardíacas, pulmonares y hepáticas) presentaron una seroprevalencia que varió entre el 89% y el 94%. Los predictores retenidos en el modelo final fueron el sexo, la edad, el año de nacimiento, los viajeros, el VIH/SIDA, la disfunción del bazo, los candidatos a trasplante, los comunicadores domésticos, la inmunosupresión relacionada con el cáncer y los profesionales sanitarios. Su área bajo la curva fue de 0,836 y el error máximo de 0,051. Los usuarios pueden hacer predicciones con una calculadora (https://pedrobrasil.shinyapps.io/INDWELL/). Los grupos con menor seroprevalencia deben ser evaluados más cuidadosamente en cuanto a la necesidad de vacunación contra hepatitis A, incluso cuando acudan a las clínicas de vacunación con otros fines.
RESUMO
The coronavirus disease 2019 pandemic abruptly changed the dynamics of basic health care, with the consequent need for adjustments in essential services. The objective of this study was to evaluate the acceptance and impact of telemedicine at a Reference Center for Special Immunobiologicals (CRIE). Methods: Patients aged 18 years or older who had a medical referral to CRIE and agreed to have a telemedicine consultation were included. After the medical appointments, participants answered a satisfaction survey. Results: From April 2021 to February 2022, 702 telemedicine consultation were conducted. Over 3,380 vaccines were prescribed via telemedicine. Of all the participants who answered the satisfaction questionnaire, 99.8% stated that they would recommend the service to other people. Conclusions: Telemedicine proved to be promising tool for healthcare at CRIE and had good acceptance by users, potentially improving access and extending the reach of the National Immunization Program.
RESUMO
Anxiety and depression are common mental disorders affecting millions of people worldwide. Unsatisfactory clinical outcomes with the use of the available pharmacological interventions among some patients demand newer drugs with proven efficacy, safety, and tolerability profile. In this study, the LQFM211, LQFM213, and LQFM214 were designed from the piperazine scaffold and administered orally in mice. These mice were later evaluated in the open field, elevated plus maze, and forced swimming tests to assess the exploratory, anxiolytic, and antidepressant-like activities, respectively. The mechanism of action of these new derivatives was evaluated using flumazenil (benzodiazepine antagonist) and WAY100635 (5-HT1A receptor antagonist). Unlike LQFM214, the LQFM211 and LQFM213 elicited anxiolytic and antidepressant-like effects. The blockade of the effect of LQFM213 by WAY100635 suggests the involvement of the serotonergic pathway.
Assuntos
Ansiolíticos , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Comportamento Animal , Humanos , Camundongos , Piperazina/farmacologia , Antagonistas da Serotonina/farmacologia , Antagonistas da Serotonina/uso terapêutico , Relação Estrutura-AtividadeRESUMO
The FDA-approved anthelmintic flubendazole has shown potential to be repositioned to treat cancer and dry macular degeneration; however, its poor water solubility limits its use. Amorphous solid dispersions may overcome this challenge, but the balance of excipients may impact the preparation method and drug release. The purpose of this study was to evaluate the influence of adjuvants and drug loading on the development of an amorphous solid dispersion of flubendazole-copovidone by hot-melt extrusion. The drug, copovidone, and adjuvants (magnesium stearate and hydroxypropyl cellulose) mixtures were statistically designed, and the process was performed in a twin-screw extruder. The study showed that flubendazole and copovidone mixtures were highly extrudable, except when drug loading was high (>40%). Furthermore, magnesium stearate positively impacted the extrusion and was more effective than hydroxypropyl cellulose. The extruded materials were evaluated by modulated differential scanning calorimetry and X-ray powder diffraction, obtaining positive amorphization and physical stability results. Pair distribution function analysis indicated the presence of drug-rich domains with medium-range order structure and no evidence of polymer-drug interaction. All extrudates presented faster dissolution (HCl, pH 1.2) than pure flubendazole, and both adjuvants had a notable influence on the dissolution rate. In conclusion, hot-melt extrusion may be a viable option to obtain stable flubendazole:copovidone amorphous dispersions.
Assuntos
Química Farmacêutica , Excipientes , Varredura Diferencial de Calorimetria , Portadores de Fármacos , Composição de Medicamentos , Temperatura Alta , Mebendazol/análogos & derivados , Pirrolidinas , Solubilidade , Compostos de VinilaRESUMO
Schistosomiasis, a tropical disease caused by flatworms, may affect the liver, spleen, bladder, and intestine. Casearia sylvestris Swartz, a medicinal plant, displays antiprotozoal, antimicrobial, antifungal, and antiulcer activities. We have evaluated the inâ vitro schistosomicidal activity of two C. sylvestris varieties against Schistosoma mansoni adult worms at concentrations between 12.5 and 200 µg/mL. At 100 and 200 µg/mL, the ethanolic C. sylvestris var. sylvestris leaf extract enriched in casearin-like diterpenes eliminated 100 % of the parasites after incubation for 72 h and 48 h, respectively, whilst the same extract at 200 µg/mL eliminated 96 %, 100 %, and 100 % of the parasites after incubation for 24, 48, and 72 h, respectively. On the other hand, the hydroalcoholic C. sylvestris var. lingua leaf extract at 200 µg/mL eliminated 60.4 and 66.7 % of the parasites after incubation for 48 and 72 h, respectively. The presence of casearin-like diterpenes and glycosylated flavonoids was confirmed based on chromatographic techniques and mass spectrometry data.
Assuntos
Casearia , Diterpenos , Plantas Medicinais , Esquistossomicidas , Casearia/química , Extratos Vegetais/química , Esquistossomicidas/farmacologiaRESUMO
BACKGROUND: Pharmacological treatments for mental disorders, such as anxiety and depression, present several limitations and adverse effects. Therefore, new pharmacotherapy with anxiolytic and antidepressant potential is necessary, and the study of compounds capable of interacting with more than one pharmacological target may provide new therapeutic options. OBJECTIVES: In this study, we proposed the design, synthesis of a new compound, 2-(4-((1- phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethyl acetate (LQFM192), pharmacological evaluation of its anxiolytic-like and antidepressant-like activities, as well as the possible mechanisms of action involved. METHODS: Administration of LQFM192 was carried out prior to the exposure of male Swiss mice to behavioral tests, such as the elevated plus-maze and forced swimming test. The involvement of the serotonergic system was studied by pretreatment with WAY-100635 or p-chlorophenylalanine (PCPA) and the involvement of the benzodiazepine site of the GABAA receptor by pretreatment with flumazenil. RESULTS: The treatment with LQFM192 at doses of 54 and 162 µmol/kg demonstrated anxiolyticlike activity that was blocked by WAY-100635, PCPA, and flumazenil pretreatments. The potential antidepressant-like activity was visualized at the same doses and blocked by WAY-100635 and PCPA. CONCLUSION: In summary, the anxiolytic-like activity of LQFM192 is mediated by the serotonergic system and the benzodiazepine site of the GABAA receptor, and the antidepressant-like activity through the serotonergic system.
Assuntos
Ansiolíticos , Acetatos , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Antidepressivos/farmacologia , Comportamento Animal , Benzodiazepinas , Flumazenil/farmacologia , Humanos , Masculino , Camundongos , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Receptores de GABA-A/metabolismoRESUMO
Silicon nitride ceramics with SiO2 , CaO, and MgO as sintering aids were investigated in view of biomedical applications. In the current study, samples with four different compositions were pressureless sintered at 1750°C for 1 h under a nitrogen atmosphere. The samples were evaluated concerning densification, microstructure, mechanical properties, and in vitro bioactivity. Microstructures with elongated ß-Si3 N4 grains dispersed in an intergranular phase and with densities from 78.77 to 97.14% of the theoretical density were obtained. Higher contents of SiO2 resulted in the best densification and mechanical properties. Besides, replacements of CaO by MgO in the initial compositions affected Young's modulus and in vitro bioactivity. Considering the samples with relative density higher than 94.14%, those with lower values of Young's modulus had lower SiO2 /MgO ratios. After immersion in SBF (Simulated Body Fluid), the samples with high porosity and/or partial replacements of CaO by MgO had their surfaces coated with a layer rich in calcium and phosphorus, morphologically similar to hydroxyapatite. Hence, producing silicon nitride ceramics with the potential to be used as orthopedic implants must consider ideal amounts of additives. In this article, the best combination of mechanical properties and mineralization capability was reached by the composition with low content of MgO, and high content of SiO2 and CaO.
Assuntos
Óxido de Magnésio , Dióxido de Silício , Materiais Biocompatíveis/química , Cerâmica/química , Durapatita , Óxido de Magnésio/química , Compostos de Silício , Dióxido de Silício/químicaRESUMO
Natural products have been largely explored as treatments for leishmaniasis, neglected diseases with few toxic therapeutic options, as scaffolds for the development of new drugs. Herein, derivatives from the aerial parts of Baccharis trimera (Less.) DC (extract and its fractions) were evaluated against Leishmania amazonensis and macrophage cells. The ethyl acetate extract was fractionated by solid-phase extraction, resulting in eight fractions (F1-F8). Fractions F3-4 were further separated into 149 subfractions; subfraction 148 (IC50-PRO = 1.56 ± 0.1 µg mL-1) was selected for purification and constituent(s) characterization by high-performance liquid chromatography, as well as 1H and 13C nuclear magnetic resonance spectroscopy. The flavonoid eupatorin (3',5-dihydroxy-4',6,7-trimethoxyflavone) was identified. This compound was 3.7 times more effective against intracellular amastigotes (IC50-AMA = 1.6 ± 0.1 µM) than amphotericin B and presented low cytotoxicity (CC50 > 100 µM), being almost 62 times more selective for the parasite, showing great potential in drug development for cutaneous leishmaniasis treatment.
Assuntos
Antiprotozoários , Baccharis , Leishmania mexicana , Leishmaniose Cutânea , Antiprotozoários/farmacologia , Baccharis/química , Flavonoides/análise , Leishmaniose Cutânea/tratamento farmacológico , Extratos Vegetais/química , Folhas de Planta/químicaRESUMO
Stone fruit cultivation is an alternative income for rural producers in Brazil, mainly for the southern region. In the specific case of plums, the lack of varieties adapted to the climatic conditions of this region is an obstacle that the research needs to resolve. In this context, the work aimed to evaluate the behaviour of the Japanese plum genotype FLA3-3 from the breeding program of the University of Florida (USA) in Ponta Grossa, Parana, Brazil, during the years 2013, 2014 and 2015. The experimental design used was entirely random. Twenty plants of the genotype under study were used, each one being a repetition. The characteristics evaluated in the field were the flowering and fruiting cycles according to the plant phenology. Physical analyzes of the fruits were carried out in the laboratory: average mass (pulp and seeds) and diameter and chemical analyze: total soluble solids, total titratable acidity and ratio. The results confirm that the genotype is precocious and the fruit harvest begins in October / November. It is adapted to the climatic condition of the municipality of Ponta Grossa, Parana, Brazil, in addition to presenting fruits within the commercial standards sought by producers and consumers. It is a viable alternative for rural producers in the region.
O cultivo da fruta com caroço é uma alternativa de renda para os produtores rurais do Brasil, principalmente da região Sul. No caso específico das ameixas, a falta de variedades adaptadas às condições climáticas da região é um entrave que a pesquisa precisa superar. Nesse contexto, o trabalho teve como objetivo avaliar o comportamento do genótipo de ameixa japonesa FLA3-3 do programa de melhoramento da Universidade da Flórida (EUA) em Ponta Grossa, Paraná, Brasil, durante os anos de 2013, 2014 e 2015. O delineamento experimental usado foi inteiramente ao acaso. Foram utilizadas vinte plantas do genótipo em estudo, cada uma sendo uma repetição. As características avaliadas em campo foram os ciclos de floração e frutificação de acordo com a fenologia da planta. As análises físicas dos frutos foram realizadas em laboratório: massa média (polpa e sementes) e diâmetro e análise química: sólidos solúveis totais, acidez total titulável e proporção. Os resultados confirmam que o genótipo é precoce e a colheita dos frutos inicia-se em outubro / novembro. Está adaptado às condições climáticas do município de Ponta Grossa, Paraná, Brasil, além de apresentar frutas dentro dos padrões comerciais buscados por produtores e consumidores, sendo uma alternativa viável para os produtores rurais da região.
Assuntos
Adaptação Fisiológica/genética , Fenômenos Químicos , Prunus domestica/crescimento & desenvolvimento , Prunus domestica/genética , Prunus domestica/químicaRESUMO
BACKGROUND: Privileged scaffolds are of high importance for molecules containing the pyrazole subunit due to their broad spectrum of pharmacological activities. For this reason, a method that is more efficient needs to be developed for the preparation of pyrazole derivatives. OBJECTIVE: The purpose of this study was the optimisation of the conventional synthesis of the pyrazole ring and the oxidation of phenyl-1H-pyrazole-4-carbaldehyde to phenyl-1H-pyrazole-4-carboxylic acid through Microwave- Assisted Organic Synthesis (MAOS). METHODS: We performed a comparison between conventional synthesis and conventional synthesis with microwave heating using the synthesis method of pyrazole ring described by Finar and Godfrey and for the oxidation of phenyl-1H-pyrazole-4-carbaldehyde, the method described by Shriner and Kleiderer was used. RESULTS: MAOS reduces the reaction time to obtain all compounds compared to conventional heating. At a temperature of 60°C, 5 minutes of reaction time, and power of 50 W, the yield of phenyl-1H-pyrazoles (3a-m) compounds was in the range of 91 - 98% using MAOS, which is better than conventional heating (72 - 90%, 75ºC, 2 hours). An improvement in the yield for the oxidation reaction was also achieved with MAOS. The compounds (5a-m) were obtained with yields ranging from 62 - 92% (80ºC, 2 minutes, 150 W), while the yields with conventional heating were in the range of 48 - 85% (80ºC, 1 hour). The 26 compounds were achieved through an easy work-up procedure with no chromatographic separation. The pure products were characterised by the spectral data obtained from IR, MS, 1H and 13C NMR or HSQC/HMBC techniques. CONCLUSION: The advantages of MAOS include short reaction time and increased yield, due to which it is an attractive option for pyrazole compounds synthesis.
Assuntos
Micro-Ondas , Pirazóis , Ácidos Carboxílicos , Técnicas de Química SintéticaRESUMO
Casearia sylvestris is an endemic tree of the Latin America that the essential oil (EO) has anti-inflammatory and gastroprotective actions. This study evaluates the chemical composition of the EO from the volatile fractions of in natura, fresh, and dried C. sylvestris var. sylvestris and var. lingua leaves. For both varieties, the dried leaves presented higher EO yield as compared to fresh leaves. The major EO chemical components were (E)-caryophyllene, α-humulene, germacrene D, bicyclogermacrene, spathulenol, caryophyllene oxide, and humulene epoxide II. In both varieties, the content of sesquiterpene hydrocarbons decreased and oxygenated sesquiterpenes increased on going from in natura to fresh and dried leaves, which indicated that leaf drying and hydrodistillation modified the volatile composition. The results also suggested that bicyclogermacrene and (E)-caryophyllene were oxidized during processing, to generate spathulenol and caryophyllene oxide, respectively. C. sylvestris varieties and in natura, fresh, and dried leaves differed in terms of the chemical composition of volatiles, which could affect the EO biological activities.