RESUMO
This study evaluated the effects of topically applied hydrogels (HG) containing nanoencapsulated indol-3-carbinol (I3C) and its free form in a rat model of skin wounds. Formulations were topically applied twice a day for five days to the wounds. On days 1, 3, and 6, the wound area was measured to verify the % of regression. On the sixth day, the animals were euthanized for the analysis of the inflammatory and oxidative profile in wounds. The nanocapsules (NC) exhibited physicochemical characteristics compatible with this kind of suspension. After five hours of exposure to ultraviolet C, more than 78% of I3C content in the suspensions was still observed. The NC-I3C did not modify the physicochemical characteristics of HG when compared to the HG base. In the in vivo study, an increase in the size of the wound was observed on the 3rd experimental day, which was lower in the treated groups (mainly in HG-NC-I3C) compared to the control. On the 6th day, HG-I3C, HG-NC-B, and HG-NC-I3C showed lower regression of the wound compared to the control. Additionally, HG-NC-I3C exhibited an anti-inflammatory effect (as observed by decreased levels of interleukin-1B and myeloperoxidase), reduced oxidative damage (by decreased reactive species, lipid peroxidation, and protein carbonylation levels), and increased antioxidant defense (by improved catalase activity and vitamin C levels) compared to the control. The current study showed more satisfactory results in the HG-NC-I3C group than in the free form of I3C in decreasing acute inflammation and oxidative damage in wounds.
I3C nanocapsules exhibited characteristics compatible with this kind of suspension;On 3rd day, I3C nanocapsules prevented the increase of wound area;I3C nanocapsules decreased oxidative damage in wound tissue;Inflammatory proteins were decreased in I3C nanocapsules treated group.
Assuntos
Indóis , Inflamação , Nanocápsulas , Estresse Oxidativo , Pele , Cicatrização , Animais , Indóis/farmacologia , Ratos , Cicatrização/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Pele/metabolismo , Nanocápsulas/química , Masculino , Ratos Wistar , Antioxidantes/farmacologiaRESUMO
BACKGROUND: The ora-pro-nóbis (Pereskia aculeata Mill.) is a plant from Brazilian biodiversity used for food and medicinal purposes. It has ample technological potential, however, it is still underutilized, being classified as a Non-Conventional Food Plant (PANC). Prospective studies in intellectual property banks make it possible to expand perspectives for scientific research, enhancing the generation of new products. OBJECTIVE: Evaluate the patents of products containing Pereskia aculeata Mill. for the areas of food and health in intellectual property databases. METHODS: The study was conducted through structured prospective investigation (collection, processing and analysis) in 4 patent databases: National Institute of Intellectual Property (INPI) - Brazil, United States Patent and Trademark Office, World Trade Organization Intellectual Property (WIPO) and Espacenet. RESULTS: The evaluation showed a reduced number of registered patents. In general, 8 patent applications were examined, of which 7 are directly associated with the species (and its derivatives) and 1 is related to a device specially designed for harvesting leaves/fruits and removing thorns. The focus of the patents was the use of the species in the food, pharmaceutical and biotechnological areas, with emphasis on the use of the leaves in the extraction of mucilage and proteins. CONCLUSION: This study showed that Pereskia aculeata Mill. is a technologically promising plant, because of its nutritional and medicinal composition, and it is important to encourage innovation and the development of new products with the species.
Assuntos
Cactaceae , Patentes como Assunto , Estados Unidos , Estudos Prospectivos , Biotecnologia , Cactaceae/metabolismo , Plantas ComestíveisRESUMO
The development of inhibitors against factor VIII (FVIII) concentrates is a severe complication of treatment for patients with haemophilia. We investigated annualized bleeding rates (ABRs) in patients in Argentina with haemophilia A with inhibitors and analysed potential differences between treatment strategies. This multicentre, retrospective, real-world data, cohort design study comprised ambulatory paediatric and adult patients with congenital haemophilia A and FVIII inhibitors treated according to standard clinical practice, with 12-months follow-up. Of 69 included patients, 39 (56.5%) received on-demand treatment, 13 (18.8%) received prophylactic treatment, and 17 (24.6%) received immune tolerance induction (ITI) therapy. The mean overall ABR was 7.68â±â8.18, with similar rates for on-demand (8.59â±â9.69), prophylaxis (5.54â±â4.71), and ITI (7.24â±â6.23) subgroups. In the negative binomial regression model, prophylactic treatment [incidence rate ratio (IRR) 0.41, 95% confidence interval (CI): 0.21-0.79, Pâ<â0.01] and ITI (IRR 0.47, 95% CI: 0.27-0.81, Pâ<â0.01) therapy were significantly associated with a decrease in the ABR compared with on-demand treatment. Age (IRR 0.96, 95% CI: 0.94-0.97, Pâ<â0.01), number of target joints (IRR 1.21, 95% CI: 1.11-1.31, Pâ<â0.001), and history of recurring bleeding (IRR 2.3, 95% CI: 1.19-4.57, Pâ=â0.012) were significantly and independently associated with ABR. The ABR in standard clinical practice was lower than that reported in controlled clinical trials. Patients undergoing prophylaxis and ITI therapy showed reduced ABRs compared with on-demand treatment, after controlling for bleeding predictor variables.
Assuntos
Hemofilia A , Adulto , Argentina , Criança , Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemorragia , Humanos , Tolerância Imunológica , Estudos RetrospectivosRESUMO
Acquired hemophilia A is an unusual bleeding disorder of autoimmune origin resulting in the formation of autoantibodies directed against coagulation factor VIII. These autoantibodies can act by partially or completely neutralizing the activation or function of the factor, or they can also accelerate its elimination from the circulation. The global incidence of the disease is 1.5 cases per million inhabitants per year. In nearly 50% of cases, an underlying disease that is presumed responsible to produce autoantibodies can be detected. We report a case with acquired hemophilia A, in a patient with Vater's ampulla adenocarcinoma.
La hemofilia adquirida A es un desorden hemorrágico inusual de origen autoinmune que resulta en la formación de autoanticuerpos dirigidos contra el factor VIII de la coagulación. Estos autoanticuerpos pueden actuar neutralizando parcial o completamente la activación o función del factor, o también pueden acelerar su eliminación de la circulación. La incidencia mundial de la enfermedad es de 1.5 casos por millón de habitantes por año. En cerca del 50% de los pacientes se puede detectar una enfermedad subyacente que se presume responsable de la producción de los autoanticuerpos. Se presenta el caso de un varón con hemofilia adquirida A, en contexto de adenocarcinoma de la ampolla de Vater.
Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Hemofilia A , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Autoanticorpos , Hemofilia A/complicações , Hemofilia A/diagnóstico , HumanosRESUMO
Resumen La hemofilia adquirida A es un desorden hemorrágico inusual de origen autoinmune que resulta en la formación de autoanticuerpos dirigidos contra el factor VIII de la coagulación. Estos autoanticuer pos pueden actuar neutralizando parcial o completamente la activación o función del factor, o también pueden acelerar su eliminación de la circulación. La incidencia mundial de la enfermedad es de 1.5 casos por millón de habitantes por año. En cerca del 50% de los pacientes se puede detectar una enfermedad subyacente que se presume responsable de la producción de los autoanticuerpos. Se presenta el caso de un varón con hemofilia adquirida A, en contexto de adenocarcinoma de la ampolla de Vater.
Abstract Acquired hemophilia A is an unusual bleeding disorder of autoimmune origin resulting in the formation of autoantibodies directed against coagulation factor VIII. These autoantibodies can act by partially or completely neutralizing the activation or function of the factor, or they can also accelerate its elimination from the circulation. The global incidence of the disease is 1.5 cases per million inhabitants per year. In nearly 50% of cases, an underlying disease that is presumed responsible to produce autoantibodies can be detected. We report a case with acquired hemophilia A, in a patient with Vater's ampulla adenocarcinoma.
Assuntos
Humanos , Ampola Hepatopancreática , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Neoplasias do Ducto Colédoco , Hemofilia A/complicações , Hemofilia A/diagnóstico , AutoanticorposRESUMO
BACKGROUND: Omeprazole (OME), a most frequently used proton pump inhibitor in gastric acidosis, is evident to show many adverse effects, including genetic instability. This study evaluated toxicogenic effects of OME in Mus musculus. METHODS: For this study, 40 male Swiss mice were divided into 8 groups (n = 5) and treated with OME at doses of 10, 20, and 40 mg/kg and/or treated with the antioxidants retinol palmitate (100 IU/kg) and ascorbic acid (2.0 µM/kg). Cyclophosphamide 50 mg/kg, (cytotoxic agent) and the vehicle were served as positive and negative control group, respectively. After 14 days of treatment, the stomach cells along with the bone marrow and peripheral blood lymphocytes were collected and submitted to the comet assay (alkaline version) and micronucleus test. Additionally, hematological and biochemical parameters of the animals were also determined inspect of vehicle group. RESULTS: The results suggest that OME at all doses induced genotoxicity and mutagenicity in the treated cells. However, in association with the antioxidants, these effects were modulated and/or inhibited along with a DNA repair capacity. CONCLUSIONS: Taken together, antioxidants (such as retinol palmitate and ascorbic acid) may be one of the best options to counteract OME-induced cytogenetic instability.
Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Diterpenos/farmacologia , Omeprazol/toxicidade , Ésteres de Retinil/farmacologia , Animais , Antineoplásicos/farmacologia , Ensaio Cometa , Ciclofosfamida/toxicidade , Reparo do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Camundongos , Mutagênese/efeitos dos fármacos , Omeprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/toxicidadeRESUMO
BACKGROUND: The glycopeptide antibiotics are a class of antimicrobial drugs that are an important alternative for cases of bacterial infections resistant to penicillins, besides being able to be used to treat infections in people allergic to pencilin. They have great activity against Gram-positive microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA), by inhibiting the cell wall synthesis. OBJECTIVE: There are many analytical methods in the literature for determination of antimicrobial glycopeptide vancomycin in different matrixes that are very effective; however, all of them use toxic solvents, contributing to the generation of waste, causing damage to the environment and to the operator, as well as increased costs of analysis. RESULTS: The most prevailing method found was high performance liquid chromatography (HPLC), followed by microbiological assays and, in less quantity, spectrometric methods. The chromatographic methods use organic solvents that are toxic, such as acetonitrile and methanol, and buffer solutions, that can damage the equipment and the column. In the microbiological assays the disc diffusion methods are still in the majority. The spectrophotometric methods were based in the UV-Vis region using buffer solutions as a diluent. CONCLUSIONS: All these methods can become greener, following green analytical chemistry principles, which could bring benefits both to the environment and the operator, and reduce costs. HIGHLIGHTS: In this paper, a literature review regarding analytical methods for determination of vancomycin was carried out with a suggestion of greener alternatives.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Vancomicina , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana , SolventesRESUMO
Traumatic brain injury (TBI) is a devastating disease frequently followed by behavioral disabilities including post-traumatic epilepsy (PTE). Although reasonable progress in understanding its pathophysiology has been made, treatment of PTE is still limited. Several studies have shown the neuroprotective effect of creatine in different models of brain pathology, but its effects on PTE is not elucidated. Thus, we decided to investigate the impact of delayed and chronic creatine supplementation on susceptibility to epileptic seizures evoked by pentylenetetrazol (PTZ) after TBI. Our experimental data revealed that 4â¯weeks of creatine supplementation (300â¯mg/kg, p.o.) initiated 1â¯week after fluid percussion injury (FPI) notably increased the latency to first myoclonic and tonic-clonic seizures, decreased the time spent in tonic-clonic seizure, seizure intensity, epileptiform discharges and spindle oscillations induced by a sub-convulsant dose of PTZ (35â¯mg/kg, i.p.). Interestingly, this protective effect persists for 1â¯week even when creatine supplementation is discontinued. The anticonvulsant effect of creatine was associated with its ability to reduce cell loss including the number of parvalbumin positive (PARV+) cells in CA3 region of the hippocampus. Furthermore, creatine supplementation also protected against the reduction of GAD67 levels, GAD activity and specific [3H]flunitrazepam binding in the hippocampus. These findings showed that chronic creatine supplementation may play a neuroprotective role on brain excitability by controlling the GABAergic function after TBI, providing a possible new strategy for the treatment of PTE.
Assuntos
Lesões Encefálicas Traumáticas/complicações , Creatina/farmacologia , Epilepsia Pós-Traumática/complicações , Epilepsia Pós-Traumática/prevenção & controle , Neurônios GABAérgicos/efeitos dos fármacos , Convulsões/complicações , Convulsões/prevenção & controle , Animais , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/patologia , Ondas Encefálicas/efeitos dos fármacos , Região CA3 Hipocampal/metabolismo , Região CA3 Hipocampal/patologia , Morte Celular/efeitos dos fármacos , Creatina/uso terapêutico , Epilepsia Pós-Traumática/tratamento farmacológico , Flunitrazepam/metabolismo , Glutamato Descarboxilase/metabolismo , Masculino , Fármacos Neuroprotetores/uso terapêutico , Pentilenotetrazol , Ensaio Radioligante , Ratos , Convulsões/induzido quimicamente , Fatores de Tempo , Trítio/metabolismoRESUMO
Eugenol is the major component of clove essential oil and has demonstrated relevant biological potential with well-known antimicrobial and antioxidant action. Therefore, this work carried out the synthesis, purification, characterization, and evaluation of the antioxidant and antibacterial potential of 19 eugenol derivatives. The derivatives were produced by esterification reactions in the hydroxyl group (-OH) of eugenol with different carboxylic acids and also by addition reactions in the double bond of the allyl group. The derivatives had a promising antibacterial potential, including a lower minimum inhibitory concentration of 500 µg/mL than eugenol (1000 µg/mL). In addition, the derivatives were active against bacterial strains (Escherichia coli, Staphylococcus aureus) that eugenol itself showed no activity, thus increasing the spectrum of antibacterial action. As for the antioxidant activity, it was observed that the derivatives that involved esterification reactions in the hydroxyl group (-OH) of the eugenol molecule's phenol resulted in a significant reduction of the antioxidant action (IC50 > 100 µg/mL) when compared with the eugenol precursor molecule (IC50 = 4.38 µg/mL). On the other hand, the structural changes located in the double bond affected much more smoothly the capacity of capturing radicals than the starting molecule, also being obtained derivatives with proximal antioxidant capacity (IC50 = 19.30 µg/mL) to commercial standards such as Trolox (IC50 = 16.00 µg/mL).
RESUMO
In order to develop bioactive lithocholic acid derivatives, we prepared fifteen semi-synthetic compounds through modification at C-3 and/or C-24. The reactions showed yields ranging from 37% to 100%. The structures of all compounds obtained were identified on the basis of their spectral data (IR, MS, 1D- and 2D-NMR). The activity of lithocholic acid and derivatives was evaluated against the growth of Escherichia coli, Staphylococcus aureus, Bacillus cereus and Pseudomonas aeruginosa. The derivative 3α-formyloxy-5ß-cholan-24-oic acid (LA-06) showed the best activity, with MIC values of 0.0790 mM against E. coli (Ec 27) and B. cereus in both cases, and 0.0395 mM against S. aureus (ATCC 12692). Lithocholic acid and the derivatives with MIC⩽1.2 mM were evaluated on the susceptibility of some bacterial pathogens to the aminoglycoside antibiotics neomycin, amikacin and gentamicin was evaluated. There are no previously reported studies about these compounds as modifiers of the action of antibiotics or any other drugs.