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1.
Recent Pat Biotechnol ; 18(2): 144-151, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37138429

RESUMO

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 Comestíveis
2.
Blood Coagul Fibrinolysis ; 32(8): 564-571, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34776503

RESUMO

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 7.68 ±â€Š8.18, with similar rates for on-demand (8.59 ±â€Š9.69), prophylaxis (5.54 ±â€Š4.71), and ITI (7.24 ±â€Š6.23) subgroups. In the negative binomial regression model, prophylactic treatment [incidence rate ratio (IRR) 0.41, 95% confidence interval (CI): 0.21-0.79, P < 0.01] and ITI (IRR 0.47, 95% CI: 0.27-0.81, P < 0.01) 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, P < 0.01), number of target joints (IRR 1.21, 95% CI: 1.11-1.31, P < 0.001), and history of recurring bleeding (IRR 2.3, 95% CI: 1.19-4.57, P = 0.012) 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 Retrospectivos
3.
Medicina (B Aires) ; 81(4): 652-655, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-34453811

RESUMO

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 , Humanos
4.
Medicina (B.Aires) ; 81(4): 652-655, ago. 2021. graf
Artigo em Espanhol | LILACS | ID: biblio-1346521

RESUMO

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 , Autoanticorpos
5.
Pharmacol Rep ; 73(2): 551-562, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33476036

RESUMO

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/toxicidade
6.
J AOAC Int ; 103(3): 755-769, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33241378

RESUMO

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 , Solventes
7.
Artigo em Inglês | MEDLINE | ID: mdl-30742861

RESUMO

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 4 weeks of creatine supplementation (300 mg/kg, p.o.) initiated 1 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 (35 mg/kg, i.p.). Interestingly, this protective effect persists for 1 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/metabolismo
8.
Toxicol Lett ; 295: 237-248, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30008432

RESUMO

Hyperammonemia is a common finding in patients with methylmalonic acidemia. However, its contribution to methylmalonate (MMA)-induced neurotoxicity is poorly understood. The aim of this study was evaluate whether an acute metabolic damage to brain during the neonatal period may disrupt cerebral development, leading to neurodevelopmental disorders, as memory deficit. Mice received a single intracerebroventricular dose of MMA and/or NH4Cl, administered 12 hs after birth. The maze tests showed that MMA and NH4Cl injected animals (21 and 40 days old) exhibited deficit in the working memory test, but not in the reference memory test. Furthermore, MMA and NH4Cl increased the levels of 2',7'-dichlorofluorescein-diacetate (DCF), TNF-α, IL-1ß in the cortex, hippocampus and striatum of mice. MMA and NH4Cl also increased glial proliferation in all structures. Since the treatment of MMA and ammonia increased cytokines levels, we suggested that it might be a consequence of the glial activation induced by the acid and ammonia, leading to delay in the developing brain and contributing to behavioral alterations. However, this hypothesis is speculative in nature and more studies are needed to clarify this possibility.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Amônia/metabolismo , Encéfalo/metabolismo , Hiperamonemia/metabolismo , Neuroglia/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/induzido quimicamente , Erros Inatos do Metabolismo dos Aminoácidos/patologia , Erros Inatos do Metabolismo dos Aminoácidos/psicologia , Cloreto de Amônio , Animais , Comportamento Animal , Encéfalo/patologia , Encéfalo/fisiopatologia , Proliferação de Células , Modelos Animais de Doenças , Fluoresceínas/metabolismo , Hiperamonemia/induzido quimicamente , Hiperamonemia/patologia , Hiperamonemia/psicologia , Interleucina-1beta/metabolismo , Masculino , Malonatos , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Transtornos da Memória/psicologia , Memória de Curto Prazo , Camundongos , Neuroglia/patologia , Compostos de Amônio Quaternário , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo
9.
Chem Cent J ; 12(1): 34, 2018 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-29611004

RESUMO

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).

10.
Brain Res ; 1655: 242-251, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27984020

RESUMO

Physical exercise can induce brain plasticity and reduce the cognitive decline observed in type 1 diabetes mellitus (T1DM). We investigated the effects of physical exercise to prevent or reverse spatial memory deficits produced by diabetes and some biochemical and immunohistochemical changes in hippocampal astrocytes of T1DM model. In this study, 56 male Wistar rats were divided in four groups: trained control (TC), non-trained control (NTC), trained diabetic (TD) and non-trained diabetic (NTD). 27 days after streptozotocin-induced (STZ) diabetes, the exercise groups were submitted to 5 weeks of aerobic exercise. All groups were assessed in place recognition (PR) test before and after training. The glial fibrillary acidic protein (GFAP) positive astrocytes were evaluated using planar morphology, optical densitometry and Sholl's concentric circles method. Glucose and glutamate uptake, reduced glutathione (GSH) and glutamine synthetase (GS) levels were measured using biochemical assays. Our main results are: 1-Exercise reverses spatial memory impairments generated by T1DM; 2-Exercise increases GSH and GS in TC but not in TD rats; 3-Exercise increases density of GFAP positive astrocytes in the TC and TD groups and increases astrocytic ramification in TD animals. Our findings indicate that physical exercise reverses the cognitive deficits present in T1DM and induces important biochemical and immunohistochemical astrocytic changes.


Assuntos
Astrócitos/fisiologia , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 1/terapia , Terapia por Exercício , Hipocampo/fisiopatologia , Transtornos da Memória/terapia , Animais , Astrócitos/patologia , Glicemia/fisiologia , Peso Corporal/fisiologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Experimental/psicologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/psicologia , Proteína Glial Fibrilar Ácida/metabolismo , Glutamato-Amônia Ligase/metabolismo , Ácido Glutâmico/metabolismo , Glutationa/metabolismo , Hipocampo/patologia , Masculino , Transtornos da Memória/patologia , Transtornos da Memória/fisiopatologia , Plasticidade Neuronal/fisiologia , Distribuição Aleatória , Ratos Wistar , Reconhecimento Psicológico/fisiologia , Corrida/fisiologia , Memória Espacial/fisiologia
11.
Steroids ; 104: 8-15, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26216208

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.


Assuntos
Antibacterianos/farmacologia , Bacillus cereus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Ácido Litocólico/análogos & derivados , Ácido Litocólico/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Bacillus cereus/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Escherichia coli/crescimento & desenvolvimento , Ácido Litocólico/síntese química , Ácido Litocólico/química , Testes de Sensibilidade Microbiana , Conformação Molecular , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/crescimento & desenvolvimento , Relação Estrutura-Atividade
12.
Nucl Med Biol ; 41(9): 772-4, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25027865

RESUMO

The use of in vivo assay to determine the biodistribution and subsequent inter-comparison with human parameters has been used since the dawn of science. The use of this type of test admits the metabolic equity among animals for inter-comparison. Thus, the use of Wistar rats in particular is quite frequent. Regarding routes of administration, there are three ways to test priority: jugular vein, intraocular (eye plexus) and caudal; there is a consensus that these three pathways behave in the same way, or at least very similar. Biodistribution studies of drugs, especially radiopharmaceuticals, have been using randomly any of these pathways believed to be effective in their likeness without worrying about your real analytic equity. In this study, we performed in vivo assay in 8 Wistar rats using 99mTc -labeled Herceptin to review the route of administration on the biodistribution result. Thus, four mice were injected via the intraocular (eye plexus), and four were injected via tail (caudal plexus). The results were quite disparate and call the attention of the scientific community to reassess the protocols for animal experiments, in order to have uniformity and fairness between the data and may represent a test for human inter-comparison of more reliable and trustworthy way.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacocinética , Bioensaio/métodos , Tecnécio/administração & dosagem , Tecnécio/farmacocinética , Animais , Feminino , Masculino , Taxa de Depuração Metabólica , Especificidade de Órgãos , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Wistar , Distribuição Tecidual , Trastuzumab
13.
Molecules ; 19(1): 1317-27, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-24451251

RESUMO

Ursolic acid, an important bioactive compound, was isolated from ethanol extract of aerial parts of Sambucus australis. In order to develop bioactive ursolic acid derivatives, two semi-synthetic compounds were obtained through modification at C-3. The antibacterial activity of the ursolic acid and its derivatives was investigated. The microdilution method was used for determination of the minimal inhibitory concentration (MIC), against twelve bacterial strains. The influence of ursolic acid and its derivatives on the susceptibility of some bacterial pathogens to the aminoglycosides antibiotics neomycin, amikacin, kanamycin and gentamicin was evaluated. The most representative synergistic effect was observed by 3ß-formyloxy-urs-12-en-28-oic acid at the concentration of 64 µg/mL in combination with kanamycin against Escherichia coli (27), a multidrug-resistant clinical isolate from sputum, with reduction of MIC value from 128 µg/mL to 8 µg/mL. Ursolic acid and its derivatives were examined for their radical scavenger activity using the DPPH assay, and showed significant activity.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Sinergismo Farmacológico , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ácido Ursólico
14.
Bioorg Med Chem ; 22(1): 135-40, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24331757

RESUMO

Leishmaniasis and fungal infections are significant diseases impacting worldwide public health. Treatments have developed greatly over time, however, there is a necessity to discover less toxic drugs, which have greater efficacy and are more economically accessible. This work conducted a screening of Cerrado species extracts: Connarus suberosus Planch. (Connaraceae), Neea theifera Oerst. (Nyctaginaceae) and Myrcia linearifolia Cambess. (Myrtaceae) against Leishmania (Leishmania) amazonensis, dermatophytes and yeasts. Leishmanicidal and antifungal tests were conducted using MTT colorimetric assay and CLSI methodology, respectively. Connarus suberosus extracts presented the most promising results against the aforementioned microorganisms, which has not been described in the literature. The root bark EtOAc extract was selected for chemical fractionation resulting in a mixture of rapanone (1) and a previously unreported compound named as suberonone (2); a mixture of ß-sitosterol (3) and stigmasterol (4); oleic acid (5); geranilgeraniol (6); and two derivatives obtained from 1 and 2 mixture. The rapanone and suberonone mixture demonstrated a MIC of 15.62 µg/mL against Candida albicans ATCC 10231.


Assuntos
Antifúngicos/farmacologia , Leishmaniose Visceral/imunologia , Lipopolissacarídeos/farmacologia , Extratos Vegetais/química , Benzoquinonas , Descoberta de Drogas , Testes de Sensibilidade Microbiana
15.
Brain Struct Funct ; 219(1): 293-302, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23288255

RESUMO

Physical exercise has an important influence on brain plasticity, which affects the neuron-glia interaction. Astrocytes are susceptible to plasticity, and induce and stabilize synapses, regulate the concentration of various molecules, and support neuronal energy metabolism. The aim of our study was to investigate whether physical exercise is capable of altering the morphology, density and expression of glial fibrillary acidic protein (GFAP) in astrocytes from the CA1 region of rat hippocampus. Thirteen male rats were divided in two groups: sedentary (n = 6) and exercise (n = 7). The animals in the exercise group were submitted to a protocol of daily physical exercise on a treadmill for four consecutive weeks. GFAP immunoreactivity was evaluated using optical densitometry and the morphological analyses were an adaptation of Sholl's concentric circles method. Our results show that physical exercise is capable of increasing the density of GFAP-positive astrocytes as well as the regional and cellular GFAP expression. In addition, physical exercise altered astrocytic morphology as shown by the increase observed in the degree of ramification in the lateral quadrants and in the length of the longest astrocytic processes in the central quadrants. Our data demonstrate important changes in astrocytes promoted by physical exercise, supporting the idea that these cells are involved in regulating neural activity and plasticity.


Assuntos
Astrócitos/citologia , Astrócitos/metabolismo , Regulação da Expressão Gênica/fisiologia , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/citologia , Condicionamento Físico Animal/fisiologia , Animais , Contagem de Células , Masculino , Ratos , Ratos Wistar
16.
Metab Brain Dis ; 29(1): 93-104, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24318482

RESUMO

Type 1 diabetes mellitus (T1DM) has been associated with long-term complications in the central nervous system, causing brain cellular dysfunctions and cognitive deficits. On the other hand, enriched environment (EE) induces experience-dependent plasticity, especially in the hippocampus, improving the performance of animals in learning and memory tasks. Thus, our objective was to investigate the influence of the EE on memory deficits, locomotion, corticosterone levels, synaptophysin (SYP) protein immunoreactivity, cell survival and microglial activation in the dentate gyrus (DG) of T1DM rat hippocampus. Male Wistar rats (21-day-old) were exposed to EE or maintained in standard housing (controls, C) for 3 months. At adulthood, the C and EE animals were randomly divided and diabetes was induced in half of them. All the animals received 4 doses of BrdU, 24 h apart. Hippocampus-dependent spatial memory, general locomotion and serum corticosterone levels were evaluated at the end of the experiment. The animals were transcardially perfused 30 days post-BrdU administration. Our results showed that EE was able to prevent/delay the development of memory deficits caused by diabetes in rats, however it did not revert the motor impairment observed in the diabetic group. SYP immunoreactivity was increased in the enriched healthy group. The EE decreased the serum corticosterone levels in diabetic adult rats and attenuated the injurious microglial activation, though without altering the decrease of the survival cell. Thus, EE was shown to help to ameliorate cognitive comorbidities associated with T1DM, possibly by reducing hyperactivity in the hypothalamic-pituitary-adrenal axis and microglial activation in diabetic animals.


Assuntos
Diabetes Mellitus Experimental/psicologia , Meio Ambiente , Hipocampo/fisiopatologia , Transtornos da Memória/prevenção & controle , Microglia/imunologia , Animais , Glicemia/análise , Encéfalo/imunologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Proteínas de Ligação ao Cálcio/análise , Corticosterona/sangue , Replicação do DNA , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/imunologia , Comportamento Exploratório , Hipocampo/imunologia , Hipocampo/metabolismo , Abrigo para Animais , Masculino , Transtornos da Memória/sangue , Transtornos da Memória/etiologia , Proteínas dos Microfilamentos/análise , Atividade Motora , Neurogênese , Distribuição Aleatória , Ratos , Ratos Wistar , Reconhecimento Psicológico , Método Simples-Cego , Aprendizagem Espacial , Estreptozocina , Sinaptofisina/análise
17.
Artigo em Inglês | MEDLINE | ID: mdl-23983783

RESUMO

Hyptis pectinata, popularly known in Brazil as "sambacaitá" or "canudinho," is an aromatic shrub largely grown in the northeast of Brazil. The leaves and bark are used in an infusion for the treatment of throat and skin inflammations, bacterial infections, pain, and cancer. Analogues of rosmarinic acid and flavonoids were obtained from the leaves of Hyptis pectinata and consisted of two new compounds, sambacaitaric acid (1) and 3-O-methyl-sambacaitaric acid (2), and nine known compounds, rosmarinic acid (3), 3-O-methyl-rosmarinic acid (4), ethyl caffeate (5), nepetoidin A (6), nepetoidin B (7), cirsiliol (8), circimaritin (9), 7-O-methylluteolin (10), and genkwanin (11). The structures of these compounds were determined by spectroscopic methods. Compounds 1-5, and 7 were evaluated in vitro against the promastigote form of L. braziliensis, and the ethanol extract. The hexane, ethyl acetate, and methanol-water fractions were also evaluated. The EtOH extract, the hexane extract, EtOAc, MeOH:H2O fractions; and compounds 1, 2 and 4 exhibited antileishmanial activity, and compound 1 was as potent as pentamidine. In contrast, compounds 3, 5, and 7 did not present activity against the promastigote form of L. braziliensis below 100 µM. To our knowledge, compounds 1 and 2 are being described for the first time.

18.
J Voice ; 27(3): 267-72, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23465524

RESUMO

This study investigated the sexual dimorphism in the recurrent laryngeal nerve (RLN) and thyroarytenoid (TA) muscle, which control the vocal fold. The RLN and TA were bilaterally studied in human specimens obtained from necropsies (seven men and seven women). Analysis of the morphometric parameters showed that the RLN of the men were significantly larger, as shown by the intraperineural area (42.5%) (P=0.006), total number of fibers (38.0%) (P=0.0002), axonal area (34.3%) (P=0.0001), axonal diameter (19.0%) (P=0.0001), and the area of the nerve occupied by myelinated fibers (34.9%) (P=0.001). By contrast, in women, our results showed that the area of the RLN occupied by endoneurial connective tissue was larger (5.7%) (P=0.001). Estimation of the fiber area and shape coefficient showed that the histologic organization of TA is similar in men and women. These results may contribute toward enhancing our understanding about the voice neurobiology.


Assuntos
Nervo Laríngeo Recorrente/anatomia & histologia , Prega Vocal/inervação , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Músculos Laríngeos/anatomia & histologia , Masculino , Pessoa de Meia-Idade , Nervo Laríngeo Recorrente/fisiologia , Caracteres Sexuais , Fatores Sexuais
19.
Pharmacol Biochem Behav ; 104: 113-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23290938

RESUMO

Extra-pyramidal symptoms (EPS) such as akinesia, dystonia, gait alteration and tremors are observed when dopamine D2-receptors are blocked by pharmacological agents such as haloperidol. These alterations produce a Parkinson disease-like state (PLS). Physical exercise has been proven to improve gait and locomotor symptoms in Parkinson's disease; we sought to elucidate the effects of physical exercise on PLS induced by chronic administration of haloperidol in rats. We used 48 rats distributed into four groups: Control, Exercise, Haloperidol, and Hal+Exe. All the animals received a daily injection of saline or haloperidol for 30 days, and the exercise groups underwent a daily 30-minute exercise protocol for 20 days. The animals were subjected to the ink-paw test, bar test and open-field test throughout the training period. The haloperidol-induced akinesia increased throughout the days of injections, but exercise was shown to alleviate it. The assessment showed shortened stride length and increased stance width with the use of haloperidol, which were significantly alleviated by exercise. These results indicate that exercise could be an interesting approach towards reducing unwanted EPS caused by haloperidol.


Assuntos
Antagonistas de Dopamina/efeitos adversos , Haloperidol/efeitos adversos , Coxeadura Animal/induzido quimicamente , Coxeadura Animal/terapia , Condicionamento Físico Animal , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Coxeadura Animal/fisiopatologia , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Condicionamento Físico Animal/fisiologia , Ratos , Ratos Wistar
20.
Muscle Nerve ; 47(1): 46-52, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23042377

RESUMO

INTRODUCTION: In this investigation we evaluated the effects of treadmill training on mechanical sensitivity and sural nerve morphology in diabetic rats. METHODS: Rats were divided into 3 groups: control (C); diabetic (D); and trained diabetic (TD). Training was performed for 8 weeks. Mechanical sensitivity was evaluated using von Frey filaments. Sural nerve analysis included fiber area, diameter, density of myelinated fibers, area occupied by connective tissue, myelin sheath thickness, and g-ratio. RESULTS: Animals in the D group had a reduced mechanical sensitivity threshold. Morphometric study showed that the D group had a smaller myelinated fiber area and diameter, higher density of fibers and area occupied by connective tissue, thinner myelin sheath, and higher g-ratio. The D group had a higher percentage of small myelinated fibers and a lower percentage of large-diameter myelinated fibers than the C and TD groups. CONCLUSION: Training prevents functional and morphological abnormalities in the sural nerve caused by diabetes.


Assuntos
Diabetes Mellitus Experimental/patologia , Neuropatias Diabéticas/patologia , Condicionamento Físico Animal/fisiologia , Nervo Sural/patologia , Percepção do Tato/fisiologia , Animais , Diabetes Mellitus Experimental/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Fibras Nervosas Mielinizadas/patologia , Estimulação Física , Ratos , Limiar Sensorial/fisiologia , Nervo Sural/fisiopatologia
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