8-hydroxy-2--deoxyguanosine and Atrophy

Cross-sectional relationships were examined between regional brain volumes and mitochondrial DNA (mtDNA) 8-hydroxy-2-deoxyguanosine (8-oxo-dG) in peripheral blood mononuclear cells (PBMCs) of 47 HIV patients [mean age 51years; 81% with HIV RNA ≤50copies/mL] on combination antiretroviral therapy. The gene-specific DNA damage and repair assay measured mtDNA 8-oxo-dG break frequency. Magnetic resonance imaging was performed at 3T. Higher mtDNA 8-oxo-dG was associated with lateral ventricular enlargement and with decreased volumes of hippocampus, pallidum, and total subcortical gray matter, suggesting the involvement of systemic mitochondrial-specific oxidative stress in chronic HIV-related structural brain changes and cognitive difficulties. Clarification of the mechanism may provide potential therapeutic targets.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Atrophy; Cross-Sectional Studies; Deoxyguanosine; DNA Damage; DNA, Mitochondrial; Female; Gray Matter; Hippocampus; HIV Infections; Humans; Leukocytes, Mononuclear; Magnetic Resonance Imaging; Male; Middle Aged; Oxidative Stress; Reactive Oxygen Species

Phthalates are widely used as plasticizer in various consumer domestic products and are known to disturb the male reproductive function in rodents. This study investigated the involvement of oxidative stress and the atrophy of the testes in pubertal rats exposed to mono-n-butyl phthalate (MBP). Four-week-old pubertal male rats were separated into three groups. In group I, 21 rats were fed rat chow containing 2 % MBP for 3 days. In group II, 21 rats were fed rat chow containing 2 % MBP for 3 days and antioxidant vitamins C (250 mg/kg/day) and E (50 mg/kg/day) were injected daily. In group III, 21 rats were fed standard rat chow and used as controls. After 3 days, each testis was weighed and the germ cell development was evaluated using the Johnsen score. The urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured as a biological marker of oxidative DNA damage. The mean testis weight was significantly lower for group I than groups II or III (p < 0.05). The mean Johnsen score was significantly lower for group I than for groups II or III (p < 0.05). Urinary 8-OHdG concentrations were higher in group I than in groups II or III. Short-time exposure to MBP may therefore induce oxidative DNA damage in rat testes, while antioxidant vitamins administered during exposure may protect against this stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Ascorbic Acid; Atrophy; Deoxyguanosine; DNA Damage; Male; Oxidative Stress; Phthalic Acids; Plasticizers; Rats; Sexual Maturation; Testis; Vitamin E

Helicobacter pylori (H pylori) infection induces chronic inflammation that can progress to gastric atrophy, intestinal metaplasia, and gastric adenocarcinoma. We have examined oxidative damage caused by Helicobacter pylori, metaplasia, and atrophy of gastric mucosal cells in patients with chronic gastritis by measuring their urinary 8-hydroxydeoxyguanosine (8-OHdG) levels.. We recruited 77 outpatients with chronic gastritis, confirmed by endoscopic examination. H pylori status was evaluated by histology (modified Giemsa staining), the H pylori stool antigen test (n=20), and the 13C urea breath test (n=27), as described in the Maastricht consensus report.. The mean amount of 8-OHdG (microg/g creatinine) in 77 subjects was 18.07 +/- 13.49 x 10(-3) microg/g creatinine. The levels of urinary 8-OHdG in the H pylori-positive gastritis patients were also significantly higher than those in the H pylori-negative gastritis patients (P=0.003, respectively, 20.42 +/- 13.33 x 10(-3) microg/g creatinine, 13.16 +/- 12.71 x 10(-3) microg/g creatinine). The level of urinary 8-OHdG was markedly higher in patients with gastric atrophy and intestinal metaplasia than in those without (P=0.000, P=0.002, respectively). There were significant correlations between levels of urinary 8-OHdG and both the atrophy score (r=0.441, P=0.000) and the intestinal metaplasia score (r=0.436, P=0.000).. Urinary 8-OHdG levels could be investigated in every patient with chronic gastritis, since it is a simple and completely noninvasive procedure. In patients with high levels of urinary 8-OHdG, endoscopic procedures or even pathological investigation may then be carried out, with the consideration that there is a high risk of intestinal metaplasia or atrophy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Atrophy; Chronic Disease; Deoxyguanosine; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Mucosa; Male; Metaplasia; Middle Aged; Prospective Studies

Oxidative DNA damage is thought to play an important part in the pathogenesis of H. pylori-induced mucosal damage. 8-OHdG is a sensitive marker of DNA oxidation and is repaired by a polymorphic glycosylase (OGG1) more effectively than by OGG1-Cys(326). The aims of this study were to ascertain the respective roles of H. pylori, cagA status and OGG1 polymorphism in determining 8-OHdG levels in benign and premalignant stomach diseases and in gastric cancer (GC). The study involved 50 GC patients (for whom both neoplastic tissue and surrounding mucosa were available), 35 with intestinal metaplasia and atrophy (IMA) and 43 controls. H. pylori and cagA status were determined by histology and polymerase chain reaction for urease and cagA. 8-OHdG was assayed using HPLC with an electrochemical detector (HPLC-ED). The OGG1 1245C-->G transversion was identified using RFLP analyses. 8-OHdG levels were significantly higher in GC, with no differences in relation to H. pylori or cagA status. OGG1 polymorphism was documented in 34% of GC (15 Ser/Cys, 2 Cys/Cys). OGG1 1245C-->G polymorphism was detected in 54% of IMA patients, but only 16% of controls (p = 0.0004) and coincided with significantly higher 8-OHdG levels. In the multivariate analysis, 8-OHdG levels were predicted by histotype and OGG1 status. OGG1 1245C-->G polymorphism was common in both GC and IMA, but very rare in controls, and correlated more closely with 8-OHdG levels than do H. pylori infection or cagA status.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Antigens, Bacterial; Atrophy; Bacterial Proteins; Biomarkers, Tumor; Deoxyguanosine; DNA Damage; DNA Glycosylases; Electrophoresis, Gel, Two-Dimensional; Female; Gastritis, Atrophic; Helicobacter pylori; Humans; Intestines; Male; Metaplasia; Middle Aged; Nucleic Acid Amplification Techniques; Oxidative Stress; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Predictive Value of Tests; Prospective Studies; Stomach Neoplasms; Urease

In geriatric dogs, Alzheimer-like behavior is frequently observed. This behavior has been classified by several authors using questionnaires and a correlation has been described between cognitive dysfunctions and Alzheimer-like pathology. In the present study, cognitive performance was correlated with brain pathology for 30 dogs of varying ages. Within these animals, two age-matched groups of old dogs with and without behavioral changes were compared. The behavioral changes were analyzed and scored with questionnaires and necropsy was performed to rule out any other cause for changed behavior. Measurements, (immuno)-histochemical staining and fluorescence microscopy were used to detect cortex atrophy, amyloid, rest-products of oxidative damage, demyelination and accumulations of macrophages in the brains of these dogs. Spearman rank correlation coefficients (r) were calculated and adjusted according to Bonferonni. In the whole group (young to very old dogs), the age of the animal showed a significant correlation with various behavioral changes (r = 0.7 to 0.9, P < 0.01). The dementia score correlated significantly (r = 0.6 to 0.8, P < 0.01) with all the brain lesions studied, except one, i.e. demyelination (r = -0.4, P > 0.05). These results suggest that a questionnaire can be used to diagnose Alzheimer-like changes in canine practice. Oxidative damage on a cellular and a nuclear level plays an important role in behavior changes.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Age Factors; Aging; Aldehydes; Alzheimer Disease; Amyloid beta-Peptides; Animals; Atrophy; Behavior, Animal; Cerebral Cortex; Cognition Disorders; Congo Red; Demyelinating Diseases; Deoxyguanosine; Disease Models, Animal; Dogs; Female; Immunohistochemistry; Lipofuscin; Male; Statistics, Nonparametric

We describe a 12-year-old girl, who had been medicated with theophylline for bronchial asthma and developed acute encephalopathy with refractory status epilepticus, showing bilateral mesial temporal and claustral lesions, which were evident on fluid-attenuated inversion recovery images, obtained with 1.5 T magnetic resonance imaging. To date, oxidative stress has been implicated in aging or various disorders, including inflammatory or degenerative neurological disorders. One of the oxidative stress markers, 8-hydroxydeoxyguanosine, was increased in our patient's cerebro-spinal fluid, plasma and urine. We speculate that augmented oxidative stress was associated with refractory status epilepticus in our patient, accompanying bilateral mesial temporal, claustral lesions and severe neuronal damage. Serial measurements of oxidative stress markers in acute encephalitis, encephalopathy, or status epilepticus could clarify the relationships between acute brain damage and free radicals.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acute Disease; Anticonvulsants; Atrophy; Basal Ganglia; Biomarkers; Brain; Brain Diseases, Metabolic; Bronchodilator Agents; Child; Comorbidity; Deoxyguanosine; DNA Damage; Female; Free Radicals; Humans; Magnetic Resonance Imaging; Oxidative Stress; Status Epilepticus; Temporal Lobe; Theophylline; Treatment Outcome; Up-Regulation