Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability.

While aspirin is generally effective for prevention of cardiovascular disease, considerable variation in drug response exists, resulting in some individuals displaying high on-treatment platelet reactivity. We used pharmacometabolomics to define pathways implicated in variation of response to treatment. We profiled serum samples from healthy subjects pre- and postaspirin (14 days, 81 mg/day) using mass spectrometry. We established a strong signature of aspirin exposure independent of response (15/34 metabolites changed). In our discovery (N = 80) and replication (N = 125) cohorts, higher serotonin levels pre- and postaspirin correlated with high, postaspirin, collagen-induced platelet aggregation. In a third cohort, platelets from subjects with the highest levels of serotonin preaspirin retained higher reactivity after incubation with aspirin than platelets from subjects with the lowest serotonin levels preaspirin (72 ± 8 vs. 61 ± 11%, P = 0.02, N = 20). Finally, ex vivo, serotonin strongly increased platelet reactivity after platelet incubation with aspirin (+20%, P = 4.9 × 10(-4), N = 12). These results suggest that serotonin is implicated in aspirin response variability.

Cancer cell proliferation is inhibited by specific modulation frequencies.

BACKGROUND: There is clinical evidence that very low and safe levels of amplitude-modulated electromagnetic fields administered via an intrabuccal spoon-shaped probe may elicit therapeutic responses in patients with cancer. However, there is no known mechanism explaining the anti-proliferative effect of very low intensity electromagnetic fields. METHODS: To understand the mechanism of this novel approach, hepatocellular carcinoma (HCC) cells were exposed to 27.12 MHz radiofrequency electromagnetic fields using in vitro exposure systems designed to replicate in vivo conditions. Cancer cells were exposed to tumour-specific modulation frequencies, previously identified by biofeedback methods in patients with a diagnosis of cancer. Control modulation frequencies consisted of randomly chosen modulation frequencies within the same 100 Hz-21 kHz range as cancer-specific frequencies. RESULTS: The growth of HCC and breast cancer cells was significantly decreased by HCC-specific and breast cancer-specific modulation frequencies, respectively. However, the same frequencies did not affect proliferation of nonmalignant hepatocytes or breast epithelial cells. Inhibition of HCC cell proliferation was associated with downregulation of XCL2 and PLP2. Furthermore, HCC-specific modulation frequencies disrupted the mitotic spindle. CONCLUSION: These findings uncover a novel mechanism controlling the growth of cancer cells at specific modulation frequencies without affecting normal tissues, which may have broad implications in oncology.

Screening and confirmation criteria for hormone residue analysis using liquid chromatography accurate mass time-of-flight, Fourier transform ion cyclotron resonance and orbitrap mass spectrometry techniques.

An emerging trend is recognised in hormone and veterinary drug residue analysis from liquid chromatography tandem mass spectrometry (LC/MS/MS) based screening and confirmation towards accurate mass alternatives such as LC coupled with time-of-flight (TOF), Fourier transform ion cyclotron resonance (FTICR) or Fourier transform orbitrap (FT Orbitrap) MS. In this study, mass resolution and accuracy are discussed for LC/MS screening and confirmation of targeted analytes and for the identification of unknowns using the anabolic steroid stanozolol and the designer beta-agonist "Clenbuterol-R" as model substances. It is shown theoretically and experimentally that mass accuracy criteria without proper mass resolution criteria yield false compliant (false negative) results, both in MS screening and MS/MS confirmation of stanozolol. On the other hand, previous medium resolution accurate mass TOFMS/MS data of the designer beta-agonist were fully confirmed by high resolution FT Orbitrap MS(n) experiments. A discussion is initiated through a proposal for additional criteria for the use of accurate mass LC/MS technologies, to be implemented in Commission Decision 2002/657/EC.

Determination of the 2H/1H, 17O/16O, and 18O/16O isotope ratios in water by means of tunable diode laser spectroscopy at 1.39 microm.

We demonstrate the feasibility of the accurate and simultaneous measurement of the 2H/1H, 17O/16O, and 18O/16O isotope ratios in water vapor by means of tunable diode laser spectroscopy. The absorptions are due to the v1 + v3 combination band, observed using a room temperature, distributed feedback (DFB) diode laser at 1.39 microm. The precision of the instrument is approximately 3, 1, and 0.5/1000 for the 2H, 17O, and 18O isotope ratios, respectively, and is at present limited by residual optical feedback to the laser. The signal-to-noise, however, is superior to that obtained in a similar experiment using a color center laser at 2.7 microm. Replacing the current laser with a better unit, we are confident that a precision well below 1/1000 is attainable for all three isotope ratios. The diode laser apparatus is ideally suited for applications demanding a reliable, cheap, and/or portable instrument, such as the biomedical doubly labeled water method and atmospheric sensing.

The psychological and social functioning of 14 children and 12 adolescents after Ilizarov leg lengthening.

We studied the psychological and social impact of the Ilizarov leg lengthening procedure in 26 patients (aged 6-17 years), who had completed the treatment at least 2 months previously. Measurements of depression and anxiety were performed preoperatively and at follow-up. Questions about functioning at school, daily life activities and treatment-related experiences were answered by the patient and his/her parents. The school or work results showed no significant decline during the lengthening procedure. Serious sleeping problems occurred during the procedure. There was no subjective improvement in physical skill after the procedure and almost one-fourth of the children still had complaints about their leg. We conclude that the Ilizarov procedure caused no serious psychological disturbances.