Serum concentrations of folate vitamers in patients with a newly diagnosed prostate cancer or hyperplasia.

BACKGROUND: Folate is required for synthesis of methyl groups and DNA in growing cells. The association between folate and prostate cancer (PCa) is not conclusive. METHODS: We investigated concentrations of folate vitamers, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) in blood of men with PCa (n = 129) or benign prostatic hyperplasia (BPH) (n = 73) who were recruited just after the first diagnosis. RESULTS: In younger subjects <65 years, concentrations of (6S)-5-CH3-H4folate (15.3 vs. 17.7 nmol/L) or total folate (UPLC-MS/MS) (18.7 vs. 23.0 nmol/L) did not differ between men with BPH and those with PCa, while SAM was higher in the controls (128 vs. 116 nmol/L). Younger patients with low- and high grade cancer did not differ in (6S)-5-CH3-H4folate (17.8 vs. 17.3 nmol/L) or total folate (UPLC-MS/MS) (22.9 vs. 23.3 nmol/L), but SAM was lower in patients with low grade PCa (111 vs. 126 nmol/L). In the older group ≥65 years, (6S)-5-CH3-H4folate (18.4 vs. 18.2 nmol/L) and total folate (UPLC-MS/MS) (22.5 vs. 22.1 nmol/L) did not differ between BPH and PCa. Older patients with advanced tumors had lower (6S)-5-CH3-H4folate compared with those with low grade tumor (12.8 vs. 20.0 nmol/L: p = 0.013). Plasma SAM was not different between older patients and controls and was not related to PCa grade. CONCLUSIONS: Lowered serum methyl folate measured at the time of diagnosis in older patients with advanced PCa, and lowered plasma SAM in younger patients with low grade PCa suggest differential folate metabolism that may have mechanistic, prognostic or predictive values.

Determination of trimethylamine, trimethylamine N-oxide, and taurine in human plasma and urine by UHPLC-MS/MS technique.

BACKGROUND: Trimethylamine-N-oxide (TMAO) is produced in the liver from trimethylamine (TMA) and is an important cellular osmolyte and potential atherogenic factor. Taurine is involved in cholesterol metabolism and also serves as a cellular osmolyte. Given their significant biological functions, the development of reliable measurement techniques is crucial to further study their role in health and disease METHODS: A new ultrahigh performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of TMA, TMAO, and taurine in plasma and urine. The method consisted of a deproteinization step using methanol/acetonitrile (15:85) that contained 0.2% formic acid and isotope-labeled internal standards. Samples were separated by centrifugation and injected into the UHPLC system. Quantification was conducted using a triple-quadrupole mass spectrometer detector with electrospray ionization interface in positive mode. RESULTS: The limits of detection ranged from 0.08 to 0.12µmol/L. The calibration curves were linear (r≥0.999) over the range examined (0.15-400µmol/L) for all compounds. The inter- and intra-day coefficients of variations were≤14.5% for TMA and ≤8% for TMAO and taurine. TMAO and taurine were found to be stable in EDTA plasma for at least 14 months at -70°C. Mean recoveries ranged from 95% to 109% and the relative matrix effects were≤4.0%. The method was applied to study physiological and pre-analytical factors in plasma and urine samples. CONCLUSIONS: The new UHPLC-MS/MS method has good accuracy, precision, and recovery. The assay combines simple sample processing with a short run time, making it well suited for high-throughput routine clinical or research purposes.

Choline-phospholipids inter-conversion is altered in elderly patients with prostate cancer.

BACKGROUND: Choline is an important source of phospholipids and methyl groups in mammalian cells. High demands for methyl and phospholipids in malignant cells suggest that choline metabolism may be disturbed in patients with cancer. OBJECTIVES AND METHODS: This case-control study investigated differences in concentrations of choline metabolites between 80 elderly men (age ≥ 65 years) with prostate cancer (PCa) and 51 men with benign prostatic hyperplasia (BPH). Plasma/serum concentrations of free choline, betaine, dimethylglycine, folate, total homocysteine (tHcy), cystathionine, methylmalonic acid, S-adenosyl homocysteine (SAH), S-adenosyl methionine (SAM), and phospholipids were measured. RESULTS: Men with BPH and those with PCa showed no significant differences in the concentrations of free choline (median = 9.7 vs. 10.0 µmol/L), folate (17.4 vs. 19.8 nmol/L), tHcy (16.0 vs. 16.2 µmol/L), SAH (18.8 vs. 18.2 nmol/L), and phosphatidylcholine (1634 vs. 1610 µmol/L). The concentrations of methylmalonic acid were lower in men with PCa (203 vs. 228 nmol/L) but the difference was not significant after adjusting for age. Sphingomyelin species (16:0, 18:0, 18:1, 20:0, 22:0, 22; 1, 23:0, 23:1, 24:0, 24:1, and 24:2) were significantly lower in men with PCa than in the controls (6-16% differences). Multiple regression analyses showed that the presence of PCa, statin use, choline, age, cystathionine, and methylmalonic acid were significant negative determinant of sphingomyelins, whereas phosphatidylcholine was a strong positive determinant. CONCLUSIONS: The current results support systemic alterations in phospholipids metabolism in PCa. We report on a significant decrease in plasma concentrations of sphingomyelin in elderly patients with PCa and in users of statins. The PCa-associated low sphingomyelin showed a synergy with the effect of statins. The presence of PCa was not associated with significant changes in plasma concentrations of choline or methyl metabolites. However, changes in choline absorption and tissue uptake cannot be ruled out in this study.

Measurement of concentrations of whole blood levels of choline, betaine, and dimethylglycine and their relations to plasma levels.

We aimed at developing a method for the measurement of choline and its metabolites in whole blood (WB). After an extraction step, quantification of choline, betaine, and dimethylglycine (DMG) was performed using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Plasma and WB metabolites were evaluated in a group of 61 elderly people. The calibration curves were linear (r(2)>0.997) for all compounds. The inter- and intra-assay coefficients of variation for all analytes were <10%. The recoveries were >90% and the relative matrix effect were ≤4.0%. The median concentrations of choline, betaine, and DMG were 11.3, 27.8, and 5.9µmol/L in plasma and 66.6, 165, and 13.7µmol/L in WB, respectively. There were positive correlations between WB and plasma markers; for choline (r=0.42), betaine (r=0.61), and DMG (r=0.56) (all p≤0.001). The concentrations of betaine in WB and plasma were significantly higher in men than in women. The concentrations of WB choline and DMG did not differ significantly according to sex. In conclusion, we have established a reliable method for measuring choline metabolites in WB. The concentrations of WB choline, betaine, and DMG seem to reflect intracellular concentrations of these metabolites.

The role of choline in prostate cancer.

Choline is an essential nutrient that is necessary for cell membrane synthesis and phospholipid metabolism and functions as an important methyl donor. Multiple roles for choline in cancer development have been suggested. Choline can affect DNA methylation and lead to a disruption of DNA repair. It can also modify cell signaling that is mediated by intermediary phospholipid metabolites, and it can support the synthesis of cell membranes and thus support cell proliferation. A higher intake or status of choline in plasma and tissues has been related to higher cancer risks. Prostate cancer shows elevated levels of choline uptake and levels of certain choline metabolites. Choline metabolites can be used as potential prognostic biomarkers for the management of prostate cancer patients. Targeting certain enzymes, which are related to choline metabolism, provides promising therapeutic opportunities for tumor growth arrest. This review summarizes the potential role of choline metabolism in cancer, especially in prostate cancer.

Diagnostic performances of anti-cyclic citrullinated peptide antibodies type IgM, IgA and IgG in Syrian patients with rheumatoid arthritis.

BACKGROUND: To determine the diagnostic performances of anti-cyclic citrullinated peptide antibodies (anti-CCP) type IgM, IgA and IgG and rheumatoid factor (RF) in Syrian patients with rheumatoid arthritis. METHODS: 64 patients with rheumatoid arthritis were included in our study. Anti-CCP IgM, IgA and IgG and rheumatoid factor (RF) were detected using ELISA. Blood samples were collected from patients with definite rheumatoid arthritis according to (ACR) criteria in Al Mwasaa University Hospital and Al Assad University Hospital, Damascus, Syria, from December 2007 to December 2008. RESULTS: The sensitivity of anti-CCP IgG was 71.9% and specificity was 100%, Whereas the sensitivity of anti-CCP IgM was 70.3% and specificity was 64%, the sensitivity of anti-CCP IgA was 43.75% and specificity was 100%, RF IgM showed a sensitivity of 70.3% and a specificity of 96%, and anti-CCP IgG prevalence in patients with negative RF was 31.6%. All tests showed no correlation with gender in RA patients. CONCLUSIONS: This study demonstrates that anti-CCP IgG is a highly specific marker for RA and has diagnostic value especially in RF negative patients.