Blood volatile compounds as biomarkers for colorectal cancer.

Many recent studies have focused on the connection between the composition of specific volatile organic compounds (VOCs) in exhaled breath and various forms of cancer. However, the composition of exhaled breath is affected by many factors, such as lung disease, smoking, and diet. VOCs are released into the bloodstream before they are exhaled; therefore, the analysis of VOCs in blood will provide more accurate results than the analysis of VOCs in exhaled breath. Blood were collected from 16 colorectal cancer patients and 20 healthy controls, then solid phase microextraction-chromatography-mass spectrometry (SPME-GC-MS) was used to analysis the exhaled volatile organic compounds (VOCs). The statistical methods principal component analysis (PCA) and partial least-squares discriminant analysis (PLSDA) were performed to deal with the final dates. Three metabolic biomarkers were found at significantly lower levels in the group of CRC patients than in the normal control group (P<0.01): phenyl methylcarbamate, ethylhexanol, and 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne. In addition, significantly higher levels of 1,1,4,4-tetramethyl-2,5-dimethylene-cyclohexane were found in the group of CRC patients than in the normal control group (P<0.05). Compared with healthy individuals, patients with colorectal adenocarcinoma exhibited a distinct blood metabolic profile with respect to VOCs. The analysis of blood VOCs appears to have potential clinical applications for CRC screening.

A general HPLC-UV method for the quantitative determination of curcumin analogues containing the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore in rat biomatrices.

Curcumin and its derivatives generally display favorable cytotoxic activities against a number of cancer cell types. We focus our rational antineoplastic drug design program on curcumin analogues containing the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore. Favorable outcomes from pharmacological screens of this series demanded further pharmacokinetic evaluations to determine their suitability as effective compounds in vivo. To allow such evaluations and to provide a general, sensitive, rapid and simple method for the analysis of compounds containing the 1,5-diaryl-3-oxo-pentadienyl scaffold, we developed an HPLC method with ultraviolet detection for their detection in various biological matrices of a relevant preclinical species, i.e. the rat. Our HPLC method is specific for the analysis of many members in this series in rat blood, plasma, serum and hepatic microsomes following liquid-liquid extraction with TBME (1:30, v/v). The assay procedure involves chromatographic separation on a Zorbax-Eclipse C-18 column under isocratic conditions with the mobile phase consisting of acetonitrile and ammonium acetate buffer (pH 5.0, 10mM) in different ratios depending upon the compound. The method was validated for NC 2083 in rat serum and rat liver microsomes, a potential lead compound, to demonstrate its applicability. The standard curve was linear (r(2)≥0.997) from 50 to 5000ng/mL. Intra- and inter-day precision and accuracy of the method were within USFDA specified limits. The stability of NC 2083 was established in an auto-injector, on bench-top, during freeze-thaw cycles and long-term stability at -80°C for 40 days. The method is suitable for a number of compounds containing the 1,5-diaryl-3-oxo-pentadienyl scaffold with divergent logP values with only minor adjustments in the buffer to acetonitrile ratio of the mobile phase.

Antioxidative enzymes and increased oxidative stress in depressive women.

OBJECTIVES: To investigate the activities of the main antioxidative enzymes and oxidative stress in women with depressive disorder (DD). METHODS: In 35 drug-naive women with DD and 35 age matched healthy women enzymes superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPX1), glutathione reductase (GR) and paraoxonase (PON1), concentrations of conjugated dienes (CD), reduced glutathione (GSH) and anthropometric and clinical data were investigated. RESULTS: Women with DD were found to have decreased activities of GPX1 (p<0.05), decreased concentrations of GSH (p<0.05), and increased activities of GR (p<0.05), CuZnSOD (p<0.001), and concentrations of CD (p<0.05). Activity of GPX1 was positively correlated with concentration of GSH (p<0.05). Concentrations of CD were positively correlated with TG (p<0.01). CONCLUSION: Our set of depressive women was characterized by changes indicating an increased oxidative stress, as well as by certain features of metabolic syndrome.

Investigation of oxidative stress and some antioxidants in patients with acute and chronic viral hepatitis B and the effect of interferon-alpha treatment.

OBJECTIVE: The aim of the study was to determine oxidative stress in patients with acute and chronic viral hepatitis B. DESIGN AND METHODS: 23 (11 F, 12 M) healthy controls, 23 (8 F, 15 M) patients with acute viral hepatitis B (AVHB) and 25 (9 F, 16 M) patients with chronic viral hepatitis B (CVHB) were studied. Serum malondialdehyde (MDA), conjugated dienes (CD), ALT, AST, total and direct bilirubins, beta-carotene and whole blood reduced glutathione (GSH) levels of all subjects were measured. In patients with CVHB, these parameters were measured both before and 6 months after treatment with interferon-alpha (IFN-alpha). RESULTS: MDA, CD, ALT, AST and total and direct bilirubin levels of the patients with AVHB and CVHB before treatment were significantly higher (P<0.001) whereas GSH and beta-carotene levels were lower (P<0.001) than those of the controls. MDA, CD, GSH, beta-carotene, ALT, AST and total and direct bilirubin levels of the patients with CVHB returned approximately to normal levels 6 months after treatment with IFN-alpha. CONCLUSION: Our results clearly show that patients with AVHB and CVHB are under the influence of increased oxidative stress (MDA and CD were increased) associated with lower levels of some antioxidants (beta-carotene and GSH). These impairments return to normal levels after IFN-alpha treatment of CVHB patients. These findings suggest that antioxidant supplementation might be considered in patients with acute or chronic hepatitis B.

Cardiopulmonary bypass is not associated with increased jugular venous blood free radical activity.

We have measured jugular venous oxygen saturation (sjv(O2)) and lactate, arterial and jugular venous blood levels of lipid peroxidation products--malondialdehyde (MDA) and diene conjugates as an index of free radical activity in eight adults undergoing coronary artery bypass surgery. Measurements were carried out at six specific times: T1--within 5 min before cardiopulmonary bypass (CPB), T2--within the first minute after the commencement of CPB, T3--during stable temperature (28 degrees C) on CPB, T4--during rewarming at 34 degrees C, T5--15 min after CPB and T6--at skin closure. There were no significant changes in arterial, jugular venous and arterio-jugular venous (a-jv) differences in diene conjugates and MDA. There was no correlation between sjv(O2), lactate and a-jv differences in MDA and diene conjugates. These results are not indicative of ischaemia-reperfusion injury across the cerebral circulation during hypothermic CPB.

Oxygen radical production precedes alcohol-induced acute pancreatitis in rats.

INTRODUCTION: Ethanol is involved in approximately 40% of the cases of acute pancreatitis. AIMS: To investigate the influence of ethanol on the pancreatic generation of oxygen-free radicals (OFR) in alcohol-induced acute pancreatitis as one possible pathway of proenzyme activation in this disease. METHODOLOGY: In one model of acute pancreatitis, the combination of ethanol with mild stimulation of the pancreas and short-term duct obstruction leads to acute pancreatitis within 24 hours. Pancreatic tissue and blood samples were assessed for reduced (GSH) and oxidized (GSSG) glutathione, malondialdehyde, conjugated dienes (CD), and myeloperoxidase. The histologic development of the acute pancreatitis was followed between 0.5 and 24 hours. RESULTS: Ethanol systemically decreased the radical defense system (GSSG: control 0.49 +/- 0.58, ethanol 2.76 +/- 1.44, p < 0.001; GSH: control 10.13 +/- 4.45, ethanol 9.52 +/- 3.43, p < 0.05). In the pancreas, oxygen free radicals also led to membrane peroxidation (CD: control 3.70 +/- 1.67, ethanol 6.10 +/- 2.15, p < 0.05). When alcoholic pancreatitis was induced, the level of oxygen radicals further increased (GSSG: control 0.17 +/- 0.15, ethanol 0.27 +/- 0.17, p < 0.005, pancreatitis 0.42 +/- 0.29). CONCLUSIONS: Ethanol induces the generation of oxygen radicals in pancreatic acinar cells. These levels increase upon induction of alcohol-induced pancreatitis. Similar to other models of acute pancreatitis, OFRs may therefore be involved in activating the cascade of self-digestion in alcohol-induced pancreatitis.

[Lipid peroxidation and the antioxidant blood system in dynamics of pestilential and choleraic intoxication]. / Lipidperoksidatsiia i antioksidantnaia sistema krovi v dinamike chumnoi i kholernoi intoksikatsii.

Lipid peroxidation (LPO) and activity of antioxidant system were studied spectrophotometrically in white rats developing pestilential and choleraic intoxication achieved by intraperitoneal injection of plague autolysate of vaccine EB strain in dose equivalent to DL50, cholerain endotoxin in doses DL50 and DL25 as well as combined effect of choleraic endo- and enterotoxins. With progression of the intoxication, the levels of diene conjugates and malonic dialdehyde in blood plasma and erythrocytes rose. LPO activation in plague intoxication arose in high activity of SOD and blood catalase. In choleraic intoxication the activity of the above enzymes progressively lowered.

Oxidative effects of laser photocoagulation.

Diabetic proliferative retinopathy is a common and sight-threatening condition. Oxidative stress is an integral and possibly causative part of the pathogenesis. Although laser photocoagulation is usually a beneficial treatment it remains unclear how it works. The possibility that it induces a sudden, temporary increase in free radical activity either by direct thermal damage or by oxygen reperfusion is explored in this clinical study by measuring the oxidative status in the peripheral blood of 13 patients undergoing panretinal photocoagulation. There were significant increases at one hour in malondialdehyde-like material (MDA-LM), 8.1 (6.9-9.6) nmol/mL, to 9.1 (7.6-9.8) nmol/mL, (less than 0.005); plasma thiols (PSH), 423 (352-457) microns/L, to 444 (382-478) microns/L, (p less than 0.005) and red cell reduced glutathione (GSH), 1357 (1295-1655) microns/L, to 1480 (1305-1760) microns/L, (p less than 0.01). Diene conjugates rose over the first hour 0.55 (0.36-0.79) od/mL, to 0.58 (0.34-0.85) od/mL falling to 0.56 (0.36-0.79) od/mL at 2 h but these changes were not significant. At 2 h, MDA-LM 8.4 (6.7-9.6) nmol/mL and PSH 404 (379-462) microns/L had returned to baseline but GSH remained significantly elevated 1500 (1325-1675) microns/L, (p less than 0.005 compared to baseline). This is a new observation and in some circumstances such generation of free radicals could explain the mechanism behind the complications of photocoagulation by direct or indirect damage to vascular endothelium leading to increased vascular permeability manifest as macular oedema or choroidal effusions.

[Metabolism of lipid peroxidation products in multiple sclerosis patients]. / Osobennosti obmena produktov perekisnogo okisleniia lipidov u bol'nykh rasseiannym sklerozom.

Concentration of dienic conjugates and malonic dialdehyde (metabolites of lipid peroxidation) were examined in the blood and the cerebrospinal liquor of patients suffering from disseminated sclerosis, CNS tumours complicated with neurological pathology, and osteochondrosis with the secondary radical syndrome at D4--D5 and D5--S1 levels. In patients with disseminated sclerosis no malonic dialdehyde was found in the cerebrospinal liquor, while its blood level exceeded normal 1.5 to 2 times. After hormonal therapy the situation was found to be reverse: malonic dialdehyde appeared in the cerebrospinal liquor, while its serum level dropped. This is, probably, due to a stabilization of the process and a fall of the concentrations of antioxidants in the liquor. An experiment with direct determination of the antioxidant activity in the liquor confirmed the hypothesis on migration of antioxidants from myelin to the liquor during process exacerbation. Since in cases of CNS tumours (contrary to disseminated sclerosis) malonic dialdehyde is regularly present in the cerebrospinal liquor, a test is suggested for diagnostic differentiation between atypic forms of disseminated sclerosis and CNS tumours.