RESUMO
Tetrahydrolinalool (THL) is an acyclic monoterpene alcohol, produced during linalol metabolism and also a constituent of essential oils. As described in the literature, many monoterpenes present anticonvulsant properties, and thus we became interested in evaluating the anticonvulsant activity of Tetrahydrolinalool using in mice model as well as in silico approaches. Our results demonstrated that THL increased latency to seizure onset and also reduced the mortality, in picrotoxin induced seizure tests. The results may be related to GABAergic regulation, which was also suggested in seizure testing induced by 3-mercapto-propionic acid. In the strychnine-induced seizure testing, none of the groups pretreated with THL modulated the parameters indicative of anticonvulsant effect. The electrophysiological results revealed that THL treatment reduces seizures induced by pentylenetetrazole. The in silico molecular docking studies showed that the interaction between THL and a GABAA receptor model formed a stable complex, in comparison to the crystaligraphic structure of diazepam, a structurally related ligand. In conclusion, all the evidences showed that THL presents effective anticonvulsant activity related to the GABAergic pathway, being a candidate for treatment of epileptic syndromes.
Assuntos
Monoterpenos Acíclicos , Anticonvulsivantes , Simulação de Acoplamento Molecular , Monoterpenos , Pentilenotetrazol , Convulsões , Anticonvulsivantes/farmacologia , Anticonvulsivantes/química , Anticonvulsivantes/síntese química , Animais , Camundongos , Convulsões/tratamento farmacológico , Monoterpenos/farmacologia , Monoterpenos/química , Monoterpenos/síntese química , Monoterpenos Acíclicos/farmacologia , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/síntese química , Masculino , Receptores de GABA-A/metabolismo , Receptores de GABA-A/química , Relação Estrutura-Atividade , Comportamento Animal/efeitos dos fármacos , Picrotoxina/farmacologiaRESUMO
BACKGROUND: People with disabilities tend to have greater oral health problems compared to those without disabilities. This may be due to barriers they come across in accessing dental services. OBJECTIVES: The objective of this systematic review was to provide a critical digest of the scientific literature concerning barriers and facilitators of access to oral health services for people with disabilities. METHODS: The electronic databases PubMed, Scopus, Web of Science, Latin American and Caribbean Health Sciences Literature (LILACS), and Brazilian Library of Dentistry (BBO) were searched using keywords relevant to the subject. The search was not restricted to specific languages or years of publication; all relevant studies were translated and reviewed. RESULTS: Sixteen studies including 14 articles, a doctoral thesis, and a monograph were selected, and their quality was analysed using the Downs and Black assessment tool. Barriers to dental services were divided into physical or nonphysical based on the dentist's perspective, as per the perception of parents/guardians or by the persons with disabilities. The barriers that emerged included the dentist's lack of preparation to assist people with disabilities, structural problems of access to dental offices, communication difficulties, and lack of awareness regarding the need for dental treatment for the disabled person. CONCLUSION: It is concluded that people with disabilities continue to run into complex physical, behavioural, or multidimensional barriers in accessing dental services. Improved training of dentists for the care of this population is hereby emphasized. The legal framework enabling access to dental care for people with disabilities must also be respected in each country.
RESUMO
The hypothalamic-pituitary-gonadal (HPG) axis and the somatotropic axis are influenced by nutritional factors. Calorie restriction (CR) extends lifespan but suppresses both the HPG and the somatotropic axes. Since most CR studies use a fairly severe (40%-60%) reduction of calorie intake, we hypothesized that a milder CR (20%) might not be deleterious to reproduction in male mice. To test this hypothesis, we evaluated the effects of 20% CR on testicular testosterone content and on testicular expression of genes that are relevant to testicular function and reproductive competence, including insulin-like growth factor-I, cytochrome P450 aromatase (Cyp19a1), androgen receptor, luteinizing hormone receptor, follicle-stimulating hormone receptor, cytochrome P450c17 and 3-beta-hydroxysteroid dehydrogenase/isomerase. To relate CR effects to the activity of the somatotropic axis, we have used growth hormone-resistant GHR knockout mice as well as transgenic mice overexpressing GH. Mild CR did not affect testosterone levels in testis homogenates and had little effect on expression of the examined genes in the reproductive organs. Altered activity of the GH/insulin-like growth factor-1 axis had a major impact on the parameters analyzed. The results also suggest that expression of several key genes involved in the control of testicular function is preserved under conditions of mild CR and encourage speculation that mild regimens of CR can produce longevity benefits without impairing reproduction.
Assuntos
Restrição Calórica , Regulação da Expressão Gênica/fisiologia , Longevidade/fisiologia , Reprodução/fisiologia , Testículo/metabolismo , Testosterona/biossíntese , 3-Hidroxiesteroide Desidrogenases/biossíntese , Animais , Aromatase/biossíntese , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Fator de Crescimento Insulin-Like I/biossíntese , Masculino , Camundongos , Camundongos Knockout , Receptores Androgênicos/biossíntese , Receptores do FSH/biossíntese , Receptores da Somatotropina/deficiência , Receptores da Somatotropina/metabolismoRESUMO
The somatotropic axis, the hypothalamic-pituitary-gonadal axis and the nutritional status are deeply interrelated in mammals. Calorie restriction (CR) prolongs lifespan, but usually at some cost to reproduction. Interestingly, many of the physiological characteristics of animals with interruption in the somatotropic axis are shared by CR animals. The level of CR in most studies is 30-60%. We tested if a milder (20%) CR would promote health benefits without inhibiting reproduction in four types of mice with altered somatotropic axis: Ames dwarfs, GHR-KO, and PEPCK-bGH and MT-bGH transgenics. Fertility was not altered by CR in any of the examined groups. Mild CR did not affect final body weights or relative reproductive organ weights; did not alter plasma levels of glucose, insulin, IGF-I, testosterone, progesterone or estradiol; and did not influence hepatic expression of genes related to longevity. Altered activity of the GH/IGF-I axis in the different mice models studied had a major impact on the parameters analyzed. This preliminary study encourages speculation that mild regimens of CR can produce health and longevity benefits without the "costs" of impaired reproductive potential.