Impaired Fasting Glucose & 8-Iso- Prostaglandin F2a in Diabetes Disease Progression.

Aims: The objective of the present study was to evaluate the changes of 8- isoprostaglandin F2α and other markers of oxidative stress with impaired fasting glucose when compared to non-diabetic control participants. Methodology: This is a cross-sectional study, conducted at Charles Sturt University, Albury, NSW, Australia and included 428 participants (female: male, 247:181) participants attending the Diabetes Complications Clinic in the School of Community Health for the period between January 2011 to October 2012. Results: Urinary 8-isoprostaglandin F2α was significantly greater in the impaired fasting glucose group (1.4±1.3ng/ml) compared to control group (0.68±0.5ng/ml, P= .05). The increase in urinary 8-isoprostaglandin F2α was associated with a significant elevation in serum total cholesterol (4.7±1.1mol/L, P= .04) and a significant reduction in high density lipoprotein cholesterol (1.4±0.4mmol/L, P= .02) in the impaired fasting glucose group compared to the control group. A significant negative correlation was noted between urinary 8-isoprostaglandin F2α and high-density lipoprotein cholesterol among all the participants included in this study (P= .05). Conclusions: The current study proves the importance of measuring markers of oxidative stress, expressed by urinary 8-isoprostaglandin F2α and serum lipids in managing cases of impaired fasting glucose and suggests a useful biomarker for assessing disease progression and/or remission, especially in the prediabetic state.

Assessment of Mean Vessel Density and Angiogenesis in Endometrial Carcinomas.

Objective: To evaluate the role of angiogenesis in tumor growth by the assessment of mean vessel density and to quantify angiogenesis as an important variable in endometrial cancers. Material and Methods: 53 cases of endometrial malignancies (epithelial tumors-36 cases and metastatic tumors-17 cases), were analysed for histological types, grades and features like depth of invasion and vascular invasion. Microvessel counts were performed by examining the microvessels thoroughly in terms of count, morphology and density after staining the tissues by hematoxylin & eosin stain, reticulin and immunostain (Antifactor VIII Ag). Results: On H&E stain - Microvessel density (MVD) in endometrial malignancy ranged from 3.0 - 13.5 and mean MVD was 8.78. On Reticulin stain - MVD ranged from 3.5 - 15.2 and mean MVD was 9.76. Antifactor VIII sections showed very small microvessels or even single endothelial cells with the highest total counts and the MVD ranged from 6.5- 16.8 with Mean MVD of 11.7. The counts increased with the grade of the tumor in the absence of necrosis or haemorrhage. MVD counts also increased with the stage, being 8.12 in Stage I disease, 8.65 in Stage II and 10.8 in stage III disease. Atypical hyperplasia was found to be associated with epithelial tumors in 8 cases, making it a significant finding. Conclusion: Role of angiogenesis assumes greater significance with increasing severity of lesions, higher grade and stage of the tumor and seems to have an important diagnostic and prognostic significance.

Glutathione: Glutathione Sulfide Redox Imbalance in Early Impaired Fasting Glucose.

Aim: The current study aims to examine the balance between glutathione and glutathione sulfide and how this was disturbed in patients with impaired fasting glucose (IFG) level. The study also included 8-hydroxy-2’-deoxyguanosine to provide a more comprehensive picture of the overall redox state. Methodology: A cross-sectional analysis of ninety medication free participants without reported history of cardiovascular disease and/or diabetes mellitus was undertaken with data collected from the Diabetes Complications Research Initiative database at Charles Sturt University. Fasting blood glucose, HbA1c and cholesterol as standard markers for diabetes mellitus and associated complications were measured in addition to the emerging biomarkers glutathione (GSH), glutathione disulfide (GSSG), and urinary 8- hydroxy-2’-deoxyguanosine (8OHdG). Results: The IFG group had a mean blood glucose level above 6.1mmol/L being significantly higher compared to control (P<0.001). Traditional clinical markers were all within the normal range for both groups. However the GSH/GSSG ratio (8.53±5.4 vs 6.62±2.2, P=.04) was significantly lower in the IFG group. GSH and 8OHdG, being markers for oxidative stress, were not significantly different between the two groups. Conclusion: The free radical related changes in metabolic redox pathways are linked to oxidative stress and related pathologies but may not be associated with disease progression, providing an explanation why conflicting results are presented in the literature concerning any individual biomarkers and risk of diabetes. Our study included individuals with no medication use and mild hyperglycemia (impaired fasting glucose) and indicates a pro-oxidant response to mild-moderate hyperglycemia with a moderate rise in oxidative DNA damage.

Improve Markers of Oxidative Stress and Coagulation Parameters in Response to Atorvastatin Therapy.

Aims: This study was undertaken to investigate the antioxidant effects of atorvastatin in treating cases of atherosclerosis associated with hyperlipidemia. Methodology: Forty local domestic rabbits were assigned to five groups (eight rabbits in each group): After two weeks acclimatization period, a group of 8 rabbits (Group I) were used as the baseline values of the study parameters. Another 8 rabbits were selected and maintained on standard chow diet (4% fat, 18% protein, 60% carbohydrate, and 4% fibers) throughout the experiment (12 weeks) and served as a normal diet control (Group II). The rest 24 rabbits were fed on an atherogenic diet for 8 weeks to induce atherogenesis. At the end of 8th week, a group of 8 atherogenic rabbits (Group III) were separated and sacrificed and served as an atherogenic-baseline group. The remaining 16 atherogenic rabbits were randomly allocated into two groups; first group received atherogenic diet only for the next four weeks and served as an atherogenic control (Group IV). The other group received atorvastatin (Group V). Results: Blood samples were collected for serum lipids, coagulation parameters and oxidation parameters. Results showed a significant improvement in the coagulation parameters and oxidation parameters in the atorvastatin treated group compared to the atherogenic control group (P= .01). Conclusion: This study illustrated the beneficial anti-oxidant effects of atorvastatin in treating atherosclerosis associated with hyperlipidemia.