Exogenously administered and endogenously produced melatonin reduce hyperbaric oxygen-induced oxidative stress in rat lung

Hyperbaric oxygen (HBO) is a widely used treatment modality in many diseases. A known side effect of HBO is the production of reactive oxygen species. Many antioxidants such as vitamins C and E, riboflavin and selenium have been used successfully to scavenge the reactive oxygen species caused by HBO administration. In this study, we aimed to see if melatonin, a newly discovered antioxidant, has a protective effect against the overproduction of reactive oxygen species produced by HBO in rat lung tissue. Sixty male Sprague-Dawley rats were divided into 5 groups as follows: control, daytime HBO (3 ATA, 120 min), daytime HBO plus melatonin (10 mg/kg), nighttime HBO and nighttime HBO (under light exposure). The MDA, SOD and CAT levels of daytime and nighttime HBO (under light exposure) increased significantly. This significance was not found in the daytime HBO plus melatonin and nighttime HBO groups when compared with the control. In this study, HBO caused oxidant stress, and melatonin decreased the levels of MDA, SOD and CAT. Moreover, endogenous melatonin was found to be a more effective antioxidant than exogenous 10 mg/kg melatonin.     

Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones

We investigated abnormalities of the hypothalamic-pituitary-gonadal axis and cortisol concentrations in women with fibromyalgia and chronic fatigue syndrome (CFS) who were in the follicular phase of their menstrual cycle, and whether their scores for depressive symptoms were related to levels of these hormones. A total of 176 subjects participated - 46 healthy volunteers, 68 patients with fibromyalgia, and 62 patients with CFS. We examined concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, prolactin, and cortisol. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Cortisol levels were significantly lower in patients with fibromyalgia or CFS than in healthy controls (P < 0.05); there were no significant differences in other hormone levels between the three groups. Fibromyalgia patients with high BDI scores had significantly lower cortisol levels than controls (P < 0.05), and so did CFS patients, regardless of their BDI scores (P < 0.05). Among patients without depressive symptoms, cortisol levels were lower in CFS than in fibromyalgia (P < 0.05). Our study suggests that in spite of low morning cortisol concentrations, the only abnormalities in hypothalamic-pituitary-gonadal axis hormones among follicular-phase women with fibromyalgia or CFS are those of LH levels in fibromyalgia patients with a low BDI score. Depression may lower cortisol and LH levels, or, alternatively, low morning cortisol may be a biological factor that contributes to depressive symptoms in fibromyalgia. These parameters therefore must be taken into account in future investigations.     

Molecular dynamics simulations of membrane proteins

Membrane proteins control the traffic across cell membranes and thereby play an essential role in cell function from transport of various solutes to immune response via molecular recognition. Because it is very difficult to determine the structures of membrane proteins experimentally, computational methods have been increasingly used to study their structure and function. Here we focus on two classes of membrane proteins—ion channels and transporters—which are responsible for the generation of action potentials in nerves, muscles, and other excitable cells. We describe how computational methods have been used to construct models for these proteins and to study the transport mechanism. The main computational tool is the molecular dynamics (MD) simulation, which can be used for everything from refinement of protein structures to free energy calculations of transport processes. We illustrate with specific examples from gramicidin and potassium channels and aspartate transporters how the function of these membrane proteins can be investigated using MD simulations.     

The effect of hemolysis on plasma oxidation and nitration in patients with sickle cell disease

This study aimed to determine the effect of haemolysis on plasma oxidation and nitration in sickle cell disease (SCD) patients. Blood was collected from haemoglobin (Hb)A volunteers and homozygous HbSS patients who had not received blood transfusions in the last 3 months. Haemolysis was characterised by low levels of haemoglobin and haptoglobin and high levels of reticulocyte, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), plasma cell-free haemoglobin, bilirubin, total lactate dehydrogenase (LDH) and dominance of LDH-1 isoenzyme. Plasma 8-isoprostane, protein carbonyl and nitrotyrosine levels were measured to evaluate oxidised lipids, oxidised and nitrated proteins, respectively. Plasma nitrite-nitrate levels were also determined to assess nitric oxide (NO) production in both SCD patients and controls. Markers of haemolysis were significantly evident in SCD patients compared to controls. Plasma 8-isoprostane, protein carbonyl and nitrotyrosine levels were markedly elevated in SCD patients compared to controls. Linear regression analysis revealed a significant inverse correlation between haemoglobin and reticulocyte counts and a significant positive correlation of plasma cell-free haemoglobin with protein carbonyl and nitrotyrosine levels. The obtained data shows that increased haemolysis in SCD increases plasma protein oxidation and nitration.