An organic O donor for biological hydroxylation reactions.

All biological hydroxylation reactions are thought to derive the oxygen atom from one of three inorganic oxygen donors, O2, H2O2, or H2O. Here, we have identified the organic compound prephenate as the oxygen donor for the three hydroxylation steps of the O2-independent biosynthetic pathway of ubiquinone, a widely distributed lipid coenzyme. Prephenate is an intermediate in the aromatic amino acid pathway and genetic experiments showed that it is essential for ubiquinone biosynthesis in Escherichia coli under anaerobic conditions. Metabolic labeling experiments with 18O-shikimate, a precursor of prephenate, demonstrated the incorporation of 18O atoms into ubiquinone. The role of specific iron-sulfur enzymes belonging to the widespread U32 protein family is discussed. Prephenate-dependent hydroxylation reactions represent a unique biochemical strategy for adaptation to anaerobic environments.

Body weight modulates the impact of oxytocin on chronic cold-immobilization stress response.

By activating the stress system, stress modulates various physiological parameters including food intake, energy consumption, and, consequently, body weight. The role of oxytocin in the regulation of stress and obesity cannot be disregarded. Based on these findings, we aimed to investigate the effect of intranasal oxytocin on stress response in high-fat-diet (HFD)--fed and control-diet-fed rats exposed to chronic stress. Cold-immobilization stress was applied for 5 consecutive days to male Sprague-Dawley rats fed either with a control diet (n=20) or HFD (n=20) for 6 weeks. Half of the animals in each group received oxytocin. Stress response was evaluated via plasma and salivary cortisol levels as well as elevated plus maze scores. Prefrontal cortex and hypothalamic oxytocin receptor (OxtR) expression levels were identified using western blot analysis. The results showed higher stress response in HFD-fed animals than in control animals both under basal and post-stress conditions. Oxytocin application had a prominent anxiolytic effect in the control group but an insignificant effect in the HFD group. While OxtR expression levels in the prefrontal cortex did not vary according to the body weight and oxytocin application, OxtR levels in the hypothalamus were higher in the HFD- and/or oxytocin-treated animals. Our results indicated that the peripheral and central effects of oxytocin vary with body weight. Moreover, obesity masks the anxiolytic effects of oxytocin, probably by reinforcing the stress condition via central OxtRs. In conclusion, elucidating the mechanisms underlying the central effect of oxytocin is important to cope with stress and obesity.

The impact of the Adenotonsillectomy on cardiac functions and oxidative stress.

OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) causes cardiovascular comorbidities and increased oxidative stress. Adenotonsillectomy is the first treatment option for OSAS secondary to adenotonsillar hypertrophy (ATH). This study evaluated the presence of cardiovascular changes, hypertension and oxidative stress before and after adenotonsillectomy in patients with OSAS secondary to ATH. METHODS: Patients with ATH diagnosed with OSAS by polysomnography (PSG) were included. All participants received an Echocardiography (ECHO) and 24-h ambulatory blood pressure measurement (ABPM). Serum malonyldialdehyde (MDA) and total oxidant activity (TOS) levels of oxidant parameters; total antioxidant activity (TAS), catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) levels of antioxidant parameters were measured. All patients received an adenotonsillectomy. Postoperative evaluation was performed at the 6th month. In the postoperative period, PSG, ECHO, ABPM and the oxidant-antioxidant parameter levels in the serum was repeated. RESULTS: Twenty-eight patients (13 males, 15 females; mean age 8.2 ± 2.06 years) were included in the study. In the preoperative period, concentric remodeling was observed in 14,8% of the patients, although they had no cardiovascular system complaints. The apnea-hypopnea index (AHI) scores were classified as mild in 39.3% (n = 11), moderate in 21.4% (n = 6) and severe in 39.3% (n = 11) preoperatively. In the postoperative period, 22 patients were evaluated. It was observed that the severity of OSAS decreased, ventricular functions improved, oxidant parameters decreased and antioxidant parameters increased postoperatively. CONCLUSION: Adenotonsillectomy provides a positive change in cardiovascular system parameters and an antioxidant change in the oxidative balance in patients with OSAS.

The impact of oxytocin on thiol/disulphide and malonyldialdehyde/glutathione homeostasis in stressed rats.

We aimed to investigate the impact of oxytocin on serum thiol/disulphide and malonylyldialdehyde (MDA)/glutathione balance under acute stress (AS) and chronic stress (CS) exposure in rats. Animals were allocated into control (C), AS and CS groups, then the groups subdivided as intranasal oxytocin or saline applied groups, randomly. Animals in the AS or CS groups were exposed to combined cold-immobilisation stress. Salivary corticosterone levels and elevated plus maze (EPM) scores were used to assess stress response. MDA, glutathione, thiol-disulphide levels were measured in the serum samples. Oxytocin treatment attenuated stress response regardless of the stress duration verified by lower corticosterone level and favorable profile in EPM parameters measured. Furthermore, oxytocin modulated oxidant profile suggesting lowered oxidant stress with decreased serum MDA/glutathione and disulfide/native thiol ratios. Oxytocin improves the response of organism to stress via both its anxiolytic and antioxidant effects. That's why it can be considered as a protective measure to employ methods to increase endogenous oxytocin and/or to apply exogenous oxytocin to prevent stress-induced increase in oxidant stress, which plays a pivotal role in the pathogenesis of various stress-related diseases.

In vitro and in vivo evaluation of levodopa-loaded nanoparticles for nose to brain delivery.

Parkinson's disease (PD) is a neurodegenerative disease which is characterized by the loss of dopaminergic neurons in the brain. Levodopa is the drug of choice in the treatment of PD but it exhibits low oral bioavailability (30%) and very low brain uptake due to its extensive metabolism by aromatic amino acid decarboxylase in the peripheral circulation. Moreover, levodopa has psychic, gastrointestinal, and cardiovascular side effects, and most importantly, short and frequent stimulation of dopamine receptors lead to undesirable conditions such as dyskinesia over time. The challenges are to increase the therapeutic efficiency, the bioavailability and decreasing the unfavourable side effects of levodopa. Biocompatible nano-sized drug carriers could address these challenges at molecular level. For this purpose, levodopa-loaded Poly (lactide-co-glycolide) acid nanoparticles were prepared by double emulsion-solvent evaporation method for nose to brain drug delivery. Parameters such as homogenization speed, and external and internal phase content were modified to reach the highest loading efficiency. F1-1 coded formulation showed prolonged release up to 9 h. Carbodiimide method was used for surface modification studies of nanoparticles. The efficacy of the selected nanoparticle formulation has been demonstrated by in vivo experiments in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced PD model in mice.