Tissue and plasma free amino acid detection by LC-MS/MS method in high grade glioma patients.

PURPOSE: The changes in serum amino acid profiles are evaluated in different types of cancers and screening tests were developed for estimating the risk of cancer by rapid analysis of plasma free amino acid (PFAA) levels. There is scarce evidence about the metabolomics analysis of PFAA in malignant gliomas. The aim of the present study was to identify the most promising diagnostic amino acid biomarkers that could be objectively measured for high-grade glioma and to compare their level with the tissue counterpart. METHODS: In this prospective study, we collected serum samples from 22 patients with the pathological diagnosis of high-grade diffuse glioma according to WHO 2016 classification and 22 healthy subjects, and brain tissue from 22 controls. Plasma and tissue amino acid concentrations were analyzed applying liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. RESULTS: Serum alanine, alpha-aminobutyric acid (AABA), lysine (Lys) and cysteine concentrations were significantly higher in high-grade glioma patients despite low levels of alanine and Lys in the tumor tissue. Aspartic acid, histidine and taurine were significantly decreased in both serum and tumors of glioma patients. A positive correlation was detected between tumor volumes and serum levels of latter three amino acids. CONCLUSION: This study demonstrated potential amino acids which may have diagnostic value for high-grade glioma patients by utilizing LC-MS/MS method. Our results are preliminary to compare serum and tissue levels of amino acids in patients with malignant gliomas. The data presented here may provide feature ideas about the metabolic pathways in the pathogenesis of gliomas.

Early Postnatal Metabolic Profile in Neonates With Different Birth Weight Status: A Pilot Study.

Introduction: Restricted or enhanced intrauterine growth is associated with elevated risks of early and late metabolic problems in humans. Metabolomics based on amino acid and carnitine/acylcarnitine profile may have a role in fetal and early postnatal energy metabolism. In this study, the relationship between intrauterine growth status and early metabolomics profile was evaluated. Materials and Methods: A single-center retrospective cohort study was conducted. Three hundred and sixty-one newborn infants were enrolled into the study, and they were grouped according to their birth weight percentile as small for gestational age (SGA, n = 69), appropriate for gestational age (AGA, n = 168), and large for gestational age (LGA, n = 124) infants. In all infants, amino acid and carnitine/acylcarnitine profiles with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were recorded and compared between groups. Results: LGA infants had higher levels of glutamic acid and lower levels of ornithine, alanine, and glycine (p < 0.05) when compared with AGA infants. SGA infants had higher levels of alanine and glycine levels when compared with AGA and LGA infants. Total carnitine, C0, C2, C4, C5, C10:1, C18:1, C18:2, C14-OH, and C18:2-OH levels were significantly higher and C3 and C6-DC levels were lower in SGA infants (p < 0.05). LGA infants had higher C3 and C5:1 levels and lower C18:2 and C16:1-OH levels (p < 0.05). There were positive correlations between free carnitine and phenylalanine, arginine, methionine, alanine, and glycine levels (p < 0.05). Also, a positive correlation between ponderal index and C3, C5-DC, C14, and C14:1 and a negative correlation between ponderal index and ornithine, alanine, glycine, C16:1-OH, and C18:2 were shown. Conclusion: We demonstrated differences in metabolomics possibly reflecting the energy metabolism in newborn infants with intrauterine growth problems in the early postnatal period. These differences might be the footprints of metabolic disturbances in future adulthood.

Comparison of melatonin and ozone in the prevention of reperfusion injury following unilateral testicular torsion in rats.

OBJECTIVE: To compare the efficacy of ozone with melatonin, shown as the most powerful antioxidant in attenuation of testicular ischemia/reperfusion injury, in an experimental rat model of testicular torsion/detorsion. METHODS: Twenty-four male Wistar rats were divided into 4 groups: sham-operated, torsion/detorsion, torsion/detorsion plus melatonin, and torsion/detorsion plus ozone. Melatonin (10 mg/kg) and ozone (4 mg/kg) were intraperitoneally injected daily beginning 15 minutes before detorsion for the following 7 days. At the seventh day, blood and tissue samples were obtained. Johnsen score, malondialdehyde, inhibin B, glutathione plasma total sulfhydryl group (RSH) levels, and total nitric oxide were studied. RESULTS: Torsion/detorsion caused increase in tissue malondialdehyde and total nitric oxide along with a decrease in Johnsen score, tissue and plasma inhibin B, RSH, and glutathione levels. Melatonin prevented the rise in malondialdehyde and total nitric oxide levels and improved Johnsen score, tissue and plasma inhibin B, and tissue glutathione levels, along with a decrease in plasma RSH level. Ozone showed similar results except for the total nitric oxide level. Concomitantly, in contralateral testis, melatonin and ozone induced similar changes for Johnsen score, malondialdehyde, and inhibin B (not significant) and in glutathione (significant). Melatonin decreased the total nitric oxide level in both testes and ozone increased the same parameter. CONCLUSION: On different pathways, ozone was comparable with melatonin in the amelioration of ischemia/reperfusion injury. Protective effects of ozone were associated with nitrous oxide. The potential for ozone as a treatment for torsion/detorsion therefore deserves to be further elucidated.

[Evaluation of platelet serotonin levels in migraine without aura]. / Aurasiz migrende trombosit serotonin düzeylerinin degerlendirilmesi.

OBJECTIVES: The relation between migraine and serotonin levels is not clear. Plasma serotonin levels in migraineurs were investigated in previous studies. However, in the current literature, it is stated that measurement of serotonin level in platelets is more reliable. METHODS: Thirty female migraine without aura patients who were diagnosed according to the criteria of the International Headache Society and 20 healthy controls were enrolled in the study. The Hamilton depression scale (HAM-D) was applied to all subjects and those scoring 10 and above were not considered. Fasting venous blood samples were taken from subjects in the morning. Platelet rich and poor plasma were prepared. The samples were measured with high performance liquid chromatography and platelet serotonin concentration was calculated. RESULTS: Our results suggest that migraineurs have significantly low platelet serotonin concentration compared to controls. The ratio of family history of migraine in the patient group was clearly higher than in controls. HAM-D scores were significantly higher in migraineurs than in the control group. Although there was a weak correlation between low serotonin levels and attack duration and number, there was no statistical significance. CONCLUSION: Our results suggest the role of heredity and low serotonin levels in the migraine pathogenesis. Even though all subjects enrolled in the study had scores under the depression level, HAM-D scores were higher in migraineurs than controls. This may indicate the presence of subclinical depression associated with low serotonin levels in migraineurs. Extensive studies including both serotonin and other markers during pain and pain-free periods are needed.

Bronchial hyperreactivity and airway wall thickening in obstructive sleep apnea patients.

PURPOSE: Hypoxia/reoxygenation episodes in obstructive sleep apnea (OSA) results in the alteration of the oxidative balance, leading to the development of inflammation. Airway wall thickening and inflammatory changes are suggested as a primary cause of the airway hyperresponsiveness in asthmatics. Bronchial hyperreactivity (BH) may also occur in patients with OSA. We investigated the presence of BH and airway wall thickness in OSA and correlations with inflammatory markers. MATERIALS AND METHODS: Sixteen OSA patients and ten controls without allergic diseases were prospectively studied. Plasma pro-B-type natriuretic peptide (pro-BNP), fibrinogen, D-dimer, α1-antitrypsin, and high-sensitive C-reactive protein levels were measured. Airway wall thickness was evaluated with high-resolution CT, and BH was assessed by giving each subject a methacholine challenge test. RESULTS: In OSA patients, bronchial wall thickness, fibrinogen, D-dimer, α1-antitrypsin, high sensitive C-reactive protein, and pro-BNP levels were significantly greater than those in control subjects. Among the 16 patients, three had BH on methacholine challenge. Bronchial wall thickness(mm) was positively correlated with apnea-hypopnea index (AHI: number of apneas + hypopneas/hour of sleep), BMI, respiratory arousal index, nocturnal oxygen desaturation (NOD) duration (time in minutes with a nocturnal arterial oxygen saturation of <90% during sleep), and α1-antitrypsin levels. NOD duration also correlated with pro-BNP and fibrinogen levels. CONCLUSIONS: In OSA patients, walls of central airways were thicker than normal subjects. BH may have occurred in OSA patients. NOD duration correlated with inflammatory parameters and oxygen desaturation index 3% had an effect on the thickness of bronchial walls. But overall, AHI was found to be the only independent predictor of bronchial wall thickness.

Attenuated lactate response to ischemic exercise in migraine.

BACKGROUND: Although the pathogenesis of migraine still remains unclear, certain metabolic studies done on patients with migraine indicate possible deficits in mitochondrial activity. Previously, the forearm ischemic exercise test (FIT) has been used as a screening tool to evaluate mitochondrial dysfunction in metabolic myopathies. MATERIAL/METHODS: We studied the response of migraine patients to exercise using the modified FIT and compared this to the responses in a healthy group. After baseline venous blood samples were drawn, a sphygmomanometer cuff placed around the upper arm was inflated to 30 mmHg above systolic blood pressure and the subject performed a maximal isometric contraction of the forearm flexors using a hand-grip dynamometer with a 9-contraction: 1-relaxation duty cycle for a total time of 60 seconds. RESULTS: In migraine patients, attenuated lactate response after the FIT in the 1st, 3rd and 5th minutes were significantly different when compared to the control group. CONCLUSIONS: Our results show that there may be defects in the anaerobic or proximal glycolytic pathways in migraine patients, evident in stressful situations. We also conclude that the FIT may be useful for research on migraine pathophysiology.

Serotonin dilemma in postmenopausal women: is it low or high?

OBJECTIVE: In this study, we have studied with premenopausal (PM), naturally menopausal (NM) and surgically induced menopausal (SM) women in order to investigate the differences in serum cortisol, dehydroepiandrosterone sulfate (DHEA-S), follicle stimulating hormone (FSH) and estradiol (E2) levels on serum serotonin levels. METHODS: Forty premenopausal (36.7+/-3.5 years), 40 naturally menopausal (54.2+/-8.4 years) and 38 surgically induced menopausal (55.4+/-11.2 years) women were included in the study. None of the subjects were using antidepressants or hormone replacement therapy. In NM and SM, years since menopause (YSM) were 3.16+/-1.58 and 3.36+/-1.89, respectively. Cortisol, DHEA-S, FSH and E2 levels were determined by immunochemiluminisence while serotonin levels were determined by HPLC. RESULTS: Serum serotonin levels in NM women were higher than the other two groups [144.23+/-45.29 microg/L vs 61.35+/-37.72 microg/L in SM women and 98.74+/-50.29 microg/L in PM women]. E2 and DHEA-S were positively correlated, while FSH and cortisol were negatively correlated with serotonin in NM and SM. There was no significant correlation between serotonin and age or YSM. In the PM group, there was no significant correlation between serotonin and the hormones. CONCLUSION: In conclusion, increased serotonin levels in naturally menopausal women may be a compensatory mechanism to decreased E2 levels as it is postulated that there is strong interaction between E2 and the serotoninergic system.