Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles

Saliva is a readily accessible and informative biofluid, making it ideal for the early detection of a wide range of diseases including cardiovascular, renal, and autoimmune diseases, viral and bacterial infections and, importantly, cancers. Saliva-based diagnostics, particularly those based on metabolomics technology, are emerging and offer a promising clinical strategy, characterizing the association between salivary analytes and a particular disease. Here, we conducted a comprehensive metabolite analysis of saliva samples obtained from 215 individuals (69 oral, 18 pancreatic and 30 breast cancer patients, 11 periodontal disease patients and 87 healthy controls) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). We identified 57 principal metabolites that can be used to accurately predict the probability of being affected by each individual disease. Although small but significant correlations were found between the known patient characteristics and the quantified metabolites, the profiles manifested relatively higher concentrations of most of the metabolites detected in all three cancers in comparison with those in people with periodontal disease and control subjects. This suggests that cancer-specific signatures are embedded in saliva metabolites. Multiple logistic regression models yielded high area under the receiver-operating characteristic curves (AUCs) to discriminate healthy controls from each disease. The AUCs were 0.865 for oral cancer, 0.973 for breast cancer, 0.993 for pancreatic cancer, and 0.969 for periodontal diseases. The accuracy of the models was also high, with cross-validation AUCs of 0.810, 0.881, 0.994, and 0.954, respectively. Quantitative information for these 57 metabolites and their combinations enable us to predict disease susceptibility. These metabolites are promising biomarkers for medical screening

Effect of sample storage on stability of salivary glutathione, lipid peroxidation levels, and tissue factor activity

Saliva samples are often required to be stored for longer periods of time either because of the project protocol or because of lack of funding for analysis. The effects of 6 months storage (fresh, 30, 60, 90 120, 150, and 180d) on the stability of salivary reduced glutathione (GSH), lipid peroxidation (LPO) and 90days of storage (fresh, 15, 30, 60, and 90d) on the stability of salivary tissue factor (TF) activity and the stability of saliva imprint samples at 20 C were evaluated in this study. Salivary GSH, malondialdehyde (MDA) levels as an index of LPO, and TF activities were determined using the methods of Beutler, Yagi, and Quick, respectively. Saliva imprint samples were stained with Giemsa and microscopically examined. Salivary GSH levels and TF MDA levels increased significantly after 6 months of storage at -20 C. Leucocyte, epithelium and bacterium cell counts did not significantly change at the end of 90 d of storage. Saliva samples may be stored up to 1 month at -20 C for LPO assay. For cytological examinations, saliva samples may be stored for 90 d at -20 C. Further studies are needed to determine the stability of salivary GSH, and salivary TF activity stored less than 30 days at -20 C. On the other hand, if saliva samples are required to be stored, to avoid the changes because of different storage periods, we recommend that they must be stored under the same circumstances and in the same time period. J. Clin. Lab. Anal. 23:93-98, 2009. (C) 2009 Wiley-Liss, Inc

Consumption of Pistachio Nuts Beneficially Affected Blood Lipids and Total Antioxidant Activity in Rats Fed a High-Cholesterol Diet

Although nuts are typically high in dietary fat, novel studies have shown that regular consumption of these heart-healthy foods might confer a beneficial effect on cardiovascular disease risk. In the present study, we aimed to analyse the effects of pistachio consumption on blood lipids, antioxidant activity, oxidative stress and siatic acid levels in high-fat-fed rats for 8 weeks. The oxidant-antioxidant status was evaluated by the determination of lipid peroxidation (thiobarbituric acid-reactive substances), total antioxidant activity, reduced glutathione content, activity of superoxide dismutase and total thiol levels. Furthermore, tissue damage was evaluated by total sialic acid levels in serum. Total cholesterol, triglycerides, sialic acid and thiobarbituric acid-reactive substances significantly increased whereas total antioxidant activity, reduced glutathione, total thiol levels significantly decreased in the hyperlipidaemic group compared to the control group. Pistachio consumption significantly decreased triglycerides and thiobarbituric acid-reactive substance levels and significantly increased total antioxidant activity in the hyperlipidaemic group. In conclusion, pistachio supplementation may improve blood lipids and ameliorate oxidative stress in experimental hyperlipidaemia, which may have beneficial applications in the prevention of cardiovascular diseases. However, its antioxidant mechanisms remain to be investigated

Investigation of zinc and copper levels in methimazole-induced hypothyroidism: Relation with the oxidant-antioxidant status

Zn – zinc. Abstract. Thyroid hormones are associated with the oxidative and antioxidative status of the organism. Depression of metabolism by hypothyroidism has been reported to decrease oxidant production and thus protect tissues against oxidant damage. The purpose of the present study was to investigate Zn and Cu levels in MMI-induced hypothyroidism and to show whether there is a connection between these trace elements and the oxidant-antioxidant status in experimental hypothyroidism. 3-Nitrotyrosine was measured as a marker of nitro-oxidative stress. In or-der to examine the antioxidant status of MMI-induced hypothyroidism in rats, GSH and SOD levels were de-termined as well. Significantly decreased 3-nitrotyro-sine, Cu and Zn levels were observed in our experi-mental model when compared with the controls. On the other hand, GSH and SOD levels remained con-stant. It may be suggested that Cu and Zn serve as antioxidant molecules and exert their effects in an in-direct manner to reduce oxidative stress in experi-mental hypothyroidism

Investigation of tissue factor and other hemostatic profiles in experimental hypothyroidism

The influence of thyroid failure on hemostasis has been studied and is still not well understood. These patients have high risk for cardiovascular diseases because of the lipid metabolism and procoagulant agents. But the influence of thyroid failure on hemostasis is controversial. Tissue factor (TF) has an important role in the thromboembolic state. Recent experiments have demonstrated that TF-dependent activation of the coagulation cascade plays an important role in the pathophysiology of intravascular thrombus formation. The purpose of the present study was to investigate the contributions of TF, factor VII:C (FVII:C), factor XII:C (FXII:C), and fibrinogen in experimental hypothyroidism. TF was obtained from the thyroid gland and lung tissue of 10 rats following experimental hypothyroidism induced for 30 d and compared with similar tissue from 10 control rats. Significantly increased TF activities were found in hypothyroid rats. By contrast, FVII:C level was significantly decreased when compared with the control group. In this respect it is interesting to note that a hypercoagulable state due to increased thromboplastic activity may occur. Based on those results, elevated tissue factor activities (TFa) of the patients with low thyroid dysfunction may have another risk factor for cardiovascular diseases