Dexmedetomidine, an alpha-2 adrenoceptors agonist, provides a neuroprotective effect for dopaminergic neurons in the substantia nigra and attenuates glucose imbalance in the 6-hydroxydopamine animal model of Parkinson's disease.

INTRODUCTION: Studies have shown that dexmedetomidine (DEX, an a2-adrenoceptors agonist) provides a neuroprotective effect and influences blood glucose levels. Here, we evaluated the effect of prolonged treatment with low doses of DEX on the survival rate of dopaminergic (DAergic) neurons in the substantia nigra and also serum glucose levels in 6-hydroxydopamine (6-OHDA) - induced Parkinson's disease (PD) in the rat. MATERIAL AND METHODS: The neurotoxin of 6-OHDA was injected into the medial forebrain bundle by stereotaxic surgery. DEX (25 and 50 µg/kg, i.p) and yohimbine, an a2-adrenoceptor antagonist (1 mg/kg, i.p) were administered before the surgery to the 13 weeks afterward. Apomorphine-induced rotational tests and blood sampling were carried out before the surgery and multiple weeks after that. Thirteen weeks after the surgery, the rats' brain was transcardially perfused to assess the survival rate of DAergic neurons using the tyrosine hydroxylase (TH) immunohistochemistry. RESULTS: DEX remarkably attenuated the severity of rotational behavior and reversed the progress of the PD. It also increased the number of TH-labeled neurons by up to 60%. The serum glucose levels in 6-OHDA-received rats did not change in the third and seventh weeks after the surgery but decreased significantly in the thirteenth week. Treatment with DEX prevented this decrement in glucose levels. On the other hand, Treatment with yohimbine did not affect PD symptoms and glucose levels. CONCLUSION: Our data indicate that DEX through neuroprotective activity attenuates the severity of 6-OHDA-induced PD in rats. DEX might also prevent hypoglycemia during the progress of the PD.

Unraveling the function and structure impact of deleterious missense SNPs in the human OX1R receptor by computational analysis.

The orexin/hypocretin receptor type 1 (OX1R) plays a crucial role in regulating various physiological functions, especially feeding behavior, addiction, and reward. Genetic variations in the OX1R have been associated with several neurological disorders. In this study, we utilized a combination of sequence and structure-based computational tools to identify the most deleterious missense single nucleotide polymorphisms (SNPs) in the OX1R gene. Our findings revealed four highly conserved and structurally destabilizing missense SNPs, namely R144C, I148N, S172W, and A297D, located in the GTP-binding domain. Molecular dynamics simulations analysis demonstrated that all four most detrimental mutant proteins altered the overall structural flexibility and dynamics of OX1R protein, resulting in significant changes in the structural organization and motion of the protein. These findings provide valuable insights into the impact of missense SNPs on OX1R function loss and their potential contribution to the development of neurological disorders, thereby guiding future research in this field.

A study on the correlation between smoking and non-enzymatic antioxidant factors of the saliva of healthy smokers and non-smokers / Estudo da correlação entre fumo e fatores antioxidantes não-enzimáticos na saliva de pacientes saudáveis fumantes e não fumantes

Objective: Smoking is among the most destructive habits which have numerous effects on the body.The chemical components of cigarettes destroy the anti-oxidant content of the saliva.In this study, the concentration of albumin and uric acid of healthy non-smokers and smokers was measured based on the frequency of smoking. Material and Methods:In this cross-sectional study, 26 heavy smokers, 27 normal smokers, and 29 non-smokers between the ages of 25 to 40 were selected.The subjects did not suffer from any systemic or periodontal conditions.Unstimulated saliva was collected by spitting. The level of salivary albumin was measured by Bromocresol Green, and the level of salivary uric acid was measured by the uricase method.The selected method of analysis, using SPSS software, was One-Way ANOVA. Results: Mean albumin content of saliva was 33.52 ± 1.52 mg/dl in non-smokers and 23.88 ± 8.93 mg/dl in heavy smokers.The mean uric acid concentration in non-smokers was 2.98 ± 0.79 µmol/L and in heavy smokers was 2.32 ± 0.77 mg/dL.The differences between levels of both salivary uric acid and salivary albumin were significant in heavy smokers and non-smokers(P=0.001). Conclusion: Based on the findings of this study, saliva concentrations of both Albumin and Uric Acid change based on the frequency of smoking.Decreased level of salivary albumin and decreased level of salivary uric acid can be considered as markers of the harmful effects of smoking on oral health. (AU)

Objetivo: Tabagismo está entre os hábitos mais deletérios, que causam inúmeros efeitos no organismo. Os componentes químicos do cigarro destroem os compostos anti-oxidantes da saliva. Neste estudo, a concentração de albumina e ácido úrico em pacientes saudáveis fumantes e não-fumantes foi mensurada e correlacionada coma frequência de fumo. Material e Métodos: Neste estudo transversal, 26 fumantes pesados, 27 fumantes moderados, e 29 não fumantes entre 25 e 40 anos foram incluídos. Os participantes não apresentavam nenhuma condição sistêmica ou periodontal. Saliva não estimulada foi coletada. Os níveis salivares de albumina foram avaliados por Verde de bromocresol, e o nível de ácido úrico foi mensurado pelo método de uricase. Os dados foram analisados utilizando-se One-way ANOVA no software SPSS. Resultados: A albumina salivar foi de 33.52 ±1.52 mg/dl nos não-fumantes e 23.88 ± 8.93 mg/dl nos fumantes pesados. A concentração média de ácido úrico em não-fumantes foi de 2.98 ± 0.79 µmol/L e em pacientes fumantes pesados de 2.32 ± 0.77 mg/dL. As diferenças entre os níveis de ambos, ácido úrico e albumina, foi significante entre fumantes pesados e não-fumantes (p=0.001). Conclusão: Baseados nos achados deste estudo, concentrações salivares de albumina e ácido úrico baseados na frequência de fumo. A diminuição dos níveis salivares de albumina e ácido úrico podem ser considerados marcadores dos efeitos nocivos do cigarro na saúde oral(AU)