DNA adduct formation and oxidative stress in colon and liver of Big Blue rats after dietary exposure to diesel particles

Exposure to diesel exhaust particles (DEP) via the gastrointestinal route may impose risk of cancer in the colon and liver. We investigated the effects of DEP given in the diet to Big Blue rats by quantifying a panel of markers of DNA damage and repair, mutation, oxidative damage to proteins and lipids, and antioxidative defence mechanisms in colon mucosa cells, liver tissue and the blood compartment. Seven groups of rats were fed a diet with 0, 0.2, 0.8, 2, 8, 20 or 80 mg DEP/kg feed for 21 days. DEP induced a significant increase in DNA strand breaks in colon and liver. There was no effect on oxidative DNA damage (8-oxodG) in colon or liver DNA or in the urine. However, the mRNA expression of OGG1, encoding an enzyme involved in repair of 8-oxodG, was increased by DEP in both liver and colon. DNA adduct levels measured by 32P-post-labelling were elevated in colon and liver, and the expression of ERCC1 gene was affected in liver, but not in colon. In addition to these effects, DEP exposure induced apoptosis in liver. There was no significant change in mutation frequency in colon or liver. The levels of oxidative protein modifications (oxidized arginine and proline residues) were increased in liver accompanied by enhanced vitamin C levels. In plasma, we found no significant effects on oxidative damage to proteins and lipids, antioxidant enzymes or vitamin C levels. Our data indicate that gastrointestinal exposure to DEP induces DNA adducts and oxidative stress resulting in DNA strand breaks, enhanced repair capacity of oxidative base damage, apoptosis and protein oxidation in colon mucosa cells and liver.     

Novel approach to an early assessment of a patient’s potential for neurological remission after acute spinal cord injury: Analysis of hemoglobin concentration dynamics

Context/objective: Examining hemoglobin (Hb) dynamics with regard to the potential of neurological remission in patients with traumatic spinal cord injury (TSCI).Design: Prospective Clinical Observational Study.Setting: BG Trauma Centre Ludwigshafen, Department of Paraplegiology, Rhineland-Palatinate, Germany.Methods: From 2011 to 2017 a total of 80 patients with acute spinal injury were enrolled and divided into three groups: initial neurological impairment either with (G1; n = 33) or without subsequent neurological remission (G0; n = 35) and vertebral fractures without initial neurological impairment as control group (C; n = 12). Blood samples were taken for 3 months at 11 time-points after injury. Analyses were performed using routine diagnostics.Outcome measures: Multiple logistic regression was used to determine the prognostic value of Hb regarding neurological remission respecting clinical covariates.Results: Data showed elevated mean Hb concentrations in G1 from the third day to 1 month compared to G0, Hb levels were significantly higher in G1 after 3 days (P = 0.03, G1 > G0). The final multiple logistic regression model based on this data predicting the presence of neurological remission resulted in an AUC (area under the curve) of 80.5% (CI: 67.8%–93.2%) in the ROC (receiver operating characteristic) analysis.Conclusion: Elevated Hb concentrations are associated with a higher likelihood of neurological remission. Elevated concentrations of Hb in G1 compared to G0 over time might be linked to both a better initial oxygen supply response and a decreased ECM (extracellular matrix) degradation highlighting the role of Hb as a valuable biomarker for neural regeneration after TSCI.     

Inhibitory effect of Thymus caramanicus Jalas on hyperglycemia-induced apoptosis in in vitro and in vivo models of diabetic neuropathic pain

Ethnopharmacological relevance

Since Thymus caramanicus Jalas is used as a folk medicine for the treatment of rheumatism, skin disorders, bacterial infections and diabetes and it contain antioxidant agents, we decided to investigate the possible effects of Thymus caramanicus Jalas (TCJ) extract on in vitro and in vivo models of diabetic neuropathy.

Materials and methods

The high glucose-induced cell injury in Pheochromocytoma (PC12) cells and streptozotocin-induced diabetic rats were used. Tail-flick and rotarod treadmill assessments were used to determine nociceptive threshold and motor coordination. Cell viability was determined by MTT assay test. Western blotting was performed to measurement of apoptosis markers.

Results

The data showed that elevation of glucose consecutively increases functional cell injury and apoptosis. Furthermore, diabetic rats developed thermal hyperalgesia and motor deficit. Activated caspase 3, cytochrome c release and Bax/Bcl-2 ratio were significantly increased in high glucose-treated PC12 cells and in spinal cord of diabetic animals. TCJ extract (60 and 80 µg/ml) attenuates high glucose-induced PC12 cells damage and apoptosis. In diabetic animals, TCJ extract at daily doses of 100 and 150 mg/kg ameliorated hyperalgesia and suppressed spinal apoptosis.

Conclusion

The data indicate that TCJ extract has neuroprotective effects against high glucose-induced neural damage. These protective effects are mediated, at least in part, through attenuation of neural apoptosis and suggest therapeutic potential of TCJ extract in amelioration of diabetic neuropathy.     

Dietary patterns and health-related quality of life among Iranian adolescents

Quality of Life Research - Examining the associations of a-posteriori-defined dietary patterns and health-related quality of life (HRQOL) among Iranian adolescents. This cross-sectional study was...     

Autoimmune thyroid disease is associated with a diagnosis of secondary Sjögren's syndrome in familial systemic lupus

BACKGROUND: Autoimmune thyroid disease is common in systemic lupus erythematosus (SLE). About 20% of patients with SLE have secondary Sj?gren's syndrome. METHODS: Families with more than one patient with SLE were identified. All patients met the revised classification criteria, although SLE-unaffected relatives were confirmed not to satisfy these criteria. Diagnosis of autoimmune thyroid disease and Sj?gren's syndrome was made on the basis of a review of medical records, interview and questionnaire administered to patients with SLE, and by a questionnaire administered to SLE-unaffected subjects. RESULTS: Of a total of 1138 patients with SLE, 169 had a diagnosis of Sj?gren's syndrome. Of these 50 (29.6%) patients also had autoimmune thyroid disease. Of the 939 patients with SLE with no diagnosis of Sj?gren's syndrome, 119 (12.7%) had autoimmune thyroid disease (chi2 = 20.1, p = 0.000009). There was no association of a diagnosis of hypertension with secondary Sj?gren's syndrome (42% vss 47%). Among 2291 SLE-unaffected relatives, 44 had diagnosed primary Sj?gren's syndrome and 16 (36.3%) of these also had autoimmune thyroid disease. 265 of 2247 (11.8%) subjects had autoimmune thyroid disease but no Sj?gren's syndrome (chi2 = 24.2, p<0.001). CONCLUSIONS: Autoimmune thyroid disease is found in excess among patients with SLE with a diagnosis of secondary Sj?gren's syndrome, as well as among their SLE-unaffected relatives with a diagnosis of primary Sj?gren's syndrome.     

Nutrient patterns and risk of cataract: a case-control study

AIM: To assess the relation between nutrient patterns and cataract risk. METHODS: This is a hospital-based case-control study with 97 cataract patients and 198 matched controls. Dietary consumption was collected through a valid food frequency questionnaire (FFQ). Nutrient patterns were detected by applying factor analysis. Unconditional logistic regression models were used to estimate odds ratio (ORs) and 95%CIs. RESULTS: We extracted 5 main nutrient patterns. Factor 1 included niacin, thiamin, carbohydrates, protein, zinc, vitamin B6 and sodium (sodium pattern). Factor 2 was characterized by oleic acid, monounsaturated fats, polyunsaturated fats, linoleic acid, trans fatty acid, linolenic acid, vitamin E and saturated fats (fatty acid pattern). The third factor represented high intake of vitamin B12, vitamin D, cholesterol and calcium (mixed pattern). The 4th pattern was high in intake of beta and alpha carotene, vitamin A and vitamin C (antioxidant pattern). Finally, the 5th pattern loaded heavily on docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (omega-3 pattern). In crude and multivariate analysis, the sodium pattern was associated with increased risk of cataract (OR=1.97, 95%CI: 1.09-3.96). The fatty acid pattern elevated the risk of cataract (OR=1.94, 95%CI: 1.1-3.86). Antioxidant pattern was associated with a significant 79% reduced risk (2nd category compared with the 1st). Omega-3 pattern was significantly negatively associated with risk of cataract (P=0.04). CONCLUSION: These findings imply that nutrient patterns reflecting a combined consumption of nutrients might be important in the etiology of cataract. Additional studies with more efficient designs are warranted to confirm our findings.     

Treatment of depression with E-10-hydroxynortriptyline — a pilot study on biochemical effects and pharmacokinetics

The major metabolite of nortriptyline, i.e. E-10-hydroxynortriptyline (E-10-OH-NT), was given as a racemate in increasing doses from 75 to 225 mg/day to five patients with major depressive episode. Plasma concentrations of both the (–)- and (+)-enantiomers were linearly related to the doses. The mean ratio between them was 3.6±0.53, indicating stereospecific kinetics during maintenance treatment. Lumbar punctures were performed in four of the patients before and after 3 weeks of E-10-OH-NT treatment. There was a 18% mean decrease (P<0.01) in the noradrenaline metabolite HMPG in cerebrospinal fluid (CSF), supporting previous in vitro data showing that E-10-OH-NT inhibits noradrenaline uptake in vivo. During treatment, the median depression score measured by the Montgomery-Åsberg Depression Rating Scale declined from 32 to 14 (P<0.05). As the study was open, the clinical outcome is not conclusive but does not contradict the hypothesis that E-10-OH-NT has antidepressant properties. If present at all, side effects were mild and did not interfere with the treatment.     

Effect of piroxicam on the blood-retina barrier in experimentally induced diabetes in rats

The effect of piroxicam on the blood-retina barrier was evaluated in rats with experimentally induced diabetes. Diabetes was induced in rats by intraperitoneal injection of streptozocin (STZ). Diabetic rats were divided into two equal groups: those treated with piroxicam, a long-acting platelet inhibitor, and an untreated control group. Vitreous fluorophotometry (VFP) was performed both before and two weeks after induction of diabetes and piroxicam intake. Streptozocin-induced diabetes caused an alteration in the blood-retinal barrier evidenced by an increase in vitreous fluorescein concentration in diabetic rats compared with normal rats. Piroxicam intake did not lead to significant change in vitreous fluorescein concentrations. However, the examination had to be terminated at two weeks because of cataract formation. The piroxicam treated group showed less incidence of lens opacity formation (59.1% compared to 81.8% in the untreated group, p = 0.0006). Piroxicam administration appears to protect the diabetic rat eye against lens opacification.This work was supported in part by U.S. Public Health Service Grants EY02377, EY07541 and EY08137 from the National Eye Institute, National Institutes of Health, Bethesda, MD and by the Juvenile Diabetes Foundation International and Pfizer, Inc.