Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A

Xeroderma pigmentosum group A (XPA) is a genetic disorder in DNA nucleotide excision repair (NER) with severe neurological disorders, in which oxidative stress and disturbed melatonin metabolism may be involved. Herein we confirmed the diurnal variation of melatonin metabolites, oxidative stress markers, and antioxidant power in urine of patients with XPA and age-matched controls, using enzyme-linked immunosorbent assay (ELISA). The peak of 6-sulfatoxymelatonin, a metabolite of melatonin, was seen at 6:00 in both the XPA patients and controls, though the peak value is lower, specifically in the younger age group of XPA patients. The older XPA patients demonstrated an increase in the urinary levels of 8-hydroxy-2 -deoxyguanosine and hexanoyllysine, a marker of oxidative DNA damage and lipid peroxidation, having a robust peak at 6:00 and 18:00, respectively. In addition, the urinary level of total antioxidant power was decreased in the older XPA patients. Recently, it is speculated that oxidative stress and antioxidant properties may have a diurnal variation, and the circadian rhythm is likely to influence the NER itself. We believe that the administration of melatonin has the possibility of ameliorating the augmented oxidative stress in neurodegeneration, especially in the older XPA patients, modulating the melatonin metabolism and the circadian rhythm

Changes in Cerebrospinal Fluid Biomarkers in Human Herpesvirus-6-Associated Acute Encephalopathy/Febrile Seizures

To determine the involvement of oxidative stress in the pathogenesis of acute encephalopathy associated with human herpesvirus-6 (HHV-6) infection, we measured the levels of oxidative stress markers 8-hydroxy-2′-deoxyguanosine (8-OHdG) and hexanoyl-lysine adduct (HEL), tau protein, and cytokines in cerebrospinal fluid (CSF) obtained from patients with HHV-6-associated acute encephalopathy (HHV-6 encephalopathy) (n=16) and complex febrile seizures associated with HHV-6 (HHV-6 complex FS) (n=10). We also examined changes in CSF-8OHdG and CSF-HEL levels in patients with HHV-6 encephalopathy before and after treatment with edaravone, a free radical scavenger. CSF-8-OHdG levels in HHV-6 encephalopathy and HHV-6 complex FS were significantly higher than in control subjects. In contrast, CSF-HEL levels showed no significant difference between groups. The levels of total tau protein in HHV-6 encephalopathy were significantly higher than in control subjects. In six patients with HHV-6 infection (5 encephalopathy and 1 febrile seizure), the CSF-8-OHdG levels of five patients decreased after edaravone treatment. Our results suggest that oxidative DNA damage is involved in acute encephalopathy associated with HHV-6 infection

Structural and functional definition of the specificity of a novel caspase-3 inhibitor, Ac-DNLD-CHO-1

<p><b>Copyright information:</b></p><p>Taken from "Structural and functional definition of the specificity of a novel caspase-3 inhibitor, Ac-DNLD-CHO"</p><p>http://www.biomedcentral.com/1471-2210/7/8</p><p>BMC Pharmacology 2007;7():8-8.</p><p>Published online 27 Jun 2007</p><p>PMCID:PMC1931592.</p><p></p>etric caspase substrates Ac-DNLD-MCA (●) and Ac-DEVD-CHO (○) were compared. The cleavage assay was performed as described in "Methods" The y-axis represents the concentration of MCA production (pmol) and the x-axis represents incubation period. Data indicate the mean of three independent experiments

Structural and functional definition of the specificity of a novel caspase-3 inhibitor, Ac-DNLD-CHO-5

<p><b>Copyright information:</b></p><p>Taken from "Structural and functional definition of the specificity of a novel caspase-3 inhibitor, Ac-DNLD-CHO"</p><p>http://www.biomedcentral.com/1471-2210/7/8</p><p>BMC Pharmacology 2007;7():8-8.</p><p>Published online 27 Jun 2007</p><p>PMCID:PMC1931592.</p><p></p>is was performed on 1000 random samples and analyzed by the Clustal W program [44]. The numbers at branches were determined by the bootstrap analysis, indicating the times in 1000 repeat samples. The relationships are based on full-length caspases (A) and the active site residues according to our definition (B)