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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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Serum free light chain (FLC) measurements are increasingly prominent for patients with plasma cell disorders (PCDs) in screening, prognostic stratification, and monitoring therapy responses. Objectives: We aimed to develop a sensitive, reliable, and accurate method for diagnosing PCDs that can notably decrease the time and cost of current methods. Methods: Here, we present a novel approach for FLC measurement using immunoenrichment on micro-affinity chromatography in combination with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) detection. In this study, serum free kappa (κ) and free lambda (λ) light chain (LC) levels in the serum of 105 patients were compared between the nephelometric serum FLC quantification and MALDI-TOF MS detection. Results: Cohen's kappa coefficient between the MALDI-TOF MS-based method and the FLC assay revealed an almost perfect agreement in the case of normal (negative) results (κ = 0.92; 95% confidence interval (CI): 0.837 to 0.968) and a good agreement in the case of increased (positive) results (κ = 0.76; 95% CI: 0.608 to 0.870). In Spearman's correlation analysis, the best correlation was found between serum free κ/λ ratios (r = 0.628, 0.496 to 0.732; p <0.0001). Our method showed sensitivity (92.5%) and specificity (76.3%) for discrimination between the κ/λ FLC ratio compared to the serum FLC assay. Conclusion: The proposed method can significantly contribute to diagnosing and monitoring PCDs as it can significantly be time-saving, cost-effective in FLC measurement.

Background: Alzheimer's disease is a progressive neurodegenerative disorder characterized by memory loss and cognitive impairment. The diagnosis of Alzheimer's disease according to symptomatic events is still a puzzling task. Developing a biomarker-based, low-cost, and high-throughput test, readily applicable in clinical laboratories, dramatically impacts the rapid and reliable detection of the disease., Objective: This study aimed to develop an accurate, sensitive, and reliable screening tool for diagnosing Alzheimer's disease, which can significantly reduce the cost and time of existing methods., Methods: We have employed a MALDI-TOF-MS-based methodology combined with a microaffinity chromatography enrichment approach using affinity capture resins to determine serum kappa (κ) and lambda (λ) light chain levels in control and patients with AD., Results: We observed a statistically significant difference in the kappa light chain over lambda light chain (κLC/λLC) ratios between patients with AD and controls (mean difference -0,409; % 95 CI:- 0.547 to -0.269; p<0.001). Our method demonstrated higher sensitivity (100.00%) and specificity (71.43%) for discrimination between AD and controls., Conclusion: We have developed a high-throughput screening test with a novel sample enrichment method for determining κLC/λLC ratios associated with AD diagnosis. Following further validation, we believe our test has the potential for clinical laboratories., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Beken, Abali, Yildirim Saral, Guner, Dinc, Albayrak, Ersoy, Kilercik, Halici, Bulbul, Kaya, Karabay, Ay, Eksi, Benli Aksungar, Korkmaz and Serteser.)

Ovarian cancer forms 4% of all cancers and approximately 23% of all gynecological cancers in women and is responsible for the 47% of deaths related to cancers of the genital tract of women. Tumor markers are the biochemical substances which can be detected in the presence of tumors. Generally they are either the products of tumoral tissues or secreted from the normal cells which are in the inter- action with tumoral ones. The present authors attempted to determine the efficacy of the tumor marker CA- 125 and HE4 to differentiate the malign cases from the benign adnexal masses. A total of 76 patients with the appropriate criteria were included in the study. They were divided into three groups; healthy control group (n=3 1), ones with benign masses (n=23), and ones with malign ovarian masses (n=22). In the study, when the cut-off values were accepted as 55I U/ml for CA-125 and 150 pM for HE4 in differentiation of benign and malign groups, the sensitivity was found as 59.09%, specificity 91.3%, PPV 86.67% and NPV 70% LR = +6.8. This combination gives one false positive result to every five positive cases which were detected as high. With the combination of CA-125 and HE4, the value of sensitivity was found decreased as expected, although the value of the specificity increased.

Objective: Caloric restriction (CR) is proven to be effective in increasing life span and it is well known that, nutritional habits, sleeping pattern and meal frequency have profound effects on human health. In Ramadan some Muslims fast during the day-light hours for a month, providing us a unique model of intermittent fasting (IF) in humans. In the present study, we have investigated the effects of IF versus CR on the same non-diabetic obese subjects who were followed for two years according to the growth hormone (GH)/Insulin like growth factor (IGF)-1 axis and insulin resistance., Design: Single-arm Interventional Human Study., Participants: 23 female subjects (Body Mass Index (BMI) 29-39, aged between 28-42years)., Setting: Follow-up is designed as 12 months of CR, after which there was a month of IF and 11 months of CR again, to be totally 24 months. Subjects' daily diets were aligned as low calorie diet during CR and during the IF period, the same subjects fasted for 15 hours in a day for a month and there was no daily calorie restriction. Nutritional pattern was changed as 1 meal in the evening and a late supper before sleeping and no eating and drinking during the day light hours in the IF model. Subjects made brisk walking twice a day during the whole follow-up including both CR and IF periods. BMI, Blood glucose, insulin, TSH, GH, HbA1c, IGF-1, Homa-IR and urinary acetoacetate levels were monitored once in three months and twice in the fasting month., Measurements and Results: While subjects lost 1250 ± 372g monthly during the CR, in the IF period, weight loss was decreased to 473 ± 146 g. BMI of all subjects decreased gradually and as the BMI decreased, glucose, HbA1c, insulin, Homa-IR and TSH levels were decreased. GH levels were at baseline at the beginning, increased in the first six months and stayed steady during the CR and IF period than began decreasing after the IF period, while IGF-I increased gradually during the CR period and beginning with the 7th day of IF period, it decreased and kept on decreasing till the end of the follow-up. Urinary acetoacetate levels were higher during the IF period suggesting a constant lipid catabolism., Conclusion: Our results suggest that, CR affects metabolic parameters positively which will help especially pre-diabetic and insulin resistant patients without any pharmacological approach. In addition IF without calorie restriction can enhance health and cellular resistance to disease without losing weight and those effects may be attributed to different signalling pathways and circulating ketones during IF. Changes observed during IF are probably due to the changes in eating and sleeping pattern and thus changes in metabolic rhythm., Competing Interests: None

Cyclophosphamide (Cyc) is known to cause ovotoxicity and infertility in women. Our aim is to investigate the possible ovotoxic effects of Cyc and possible antioxidant and protective effects of blue-green algae, Spirulina (Sp), in rat ovaries. Eighteen rats were given: group I (n = 6, control); group II (n = 6, CP), a single dose Cyc; group III (n = 6, Sp+Cyc), 7 days Sp+single dose Cyc. Tissue malondialdehyde (MDA) levels, superoxide dismutase (SOD), and catalase (CAT) activities are assessed biochemically. Normal and atretic primordial and primary follicle counts for all sections obtained for each ovary are calculated. Mean number of follicle counts for each group are compared. In Sp+Cyc group, tissue MDA levels were significantly lower than those in the CP and higher than those in the C group (CP > Sp+Cyc > C). Tissue SOD activity was significantly higher in Sp+Cyc group than that in the CP group and lower than that in the C group (C > Sp+Cyc > C). No statistically significant difference was found between the ovarian CAT activities in any group. Histomorphometrically, there was also no significant difference between the mean numbers of normal and atretic small follicle counts. Our results suggest that single dose Cyc has adverse effects on oxidant status of the ovaries and Sp has protective effects in Cyc-induced ovotoxicity.

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

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.

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.

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.

The objectives of this study were to characterize the effects of endothelin (ET)-1 on intestinal mucosal parameters and to assess the contribution of polymorphonuclear leukocytes (PMNs), intercellular adhesion molecule-1 (ICAM-1), and a platelet-activating factor (PAF) to the mucosal dysfunction induced by ET-1. Different concentrations of ET-1 (100, 200, and 400 pmol/kg) were infused into the superior mesenteric artery for 10 min, and tissue samples were obtained 30 min after terminating the infusion. ET-1 administration significantly elevated tissue myeloperoxidase activity, plasma carbonyl content, and tissue chemiluminescence intensity, indicating that ET-1 produces PMN infiltration and oxidant stress. Blood-to-lumen clearance of (51)Cr-EDTA significantly increased after ET-1 infusion (400 pmol/kg). Monoclonal antibodies against ICAM-1 (1A29, 2 mg/kg), antineutrophil serum, and PAF antagonist (WEB-2086, 10 mg/kg) attenuated the mucosal barrier dysfunction induced by ET-1. Overall, our data indicate that ET-1 causes PMN accumulation, oxidant stress, and mucosal dysfunction in the rat small intestine and that ET-1-induced mucosal dysfunction involves a mechanism that includes a role for PMNs, ICAM-1, and PAF.

Objective: In this study the role of 17beta-estradiol (E2) in the regulation of endothelin-1 (ET-1) mRNA expression and secretion was investigated in cultured human umbilical vein endothelial cells (HUVECs)., Methods: Endothelial cells were either deprived of or treated with 17beta-estradiol (10(-9), 10(-7) M) for 48 h. After the incubation, the effect of E2 on ET-1 gene expression was evaluated by Northern blot analysis. ET-1 release into the media was measured by radioimmunoassay after 6 h of incubation under basal conditions and upon stimulation with thrombin (4 U/ml). In addition, the cyclic guanosine 5'-monophosphate (cGMP) content of cells was assayed by immunoassay. In order to exclude the role of nitric oxide (NO) in E2-induced effects on endothelin-1 gene expression and secretion, nitric oxide synthase (NOS) inhibitor, N-nitro L-arginine methyl ester (1 mM) (L-NAME) was added to the media of some cultures., Results: Incubation of HUVECs with 10(-9) and 10(-7) M E2 for 48 h resulted in a 30 and 47% inhibition of ET-1 mRNA expression, respectively. Incubation with E2 also decreased the basal and thrombin-stimulated ET-1 release while increasing the cGMP content of cells significantly. NOS inhibitor L-NAME increased the release of ET-1 from E2-incubated cells but did not alter the ET-1 release from hormone-deprived cells. However, ET-1 secretion of E2-treated cells were significantly less than the deprived ones. Northern blot analyses also demonstrated that inhibition of NOS only partly attenuated the effect of E2 on ET-1 gene expression. In the presence of L-NAME, treatment with 10(-7) M E2 caused a 12% decrease in ET-1 gene expression., Conclusion: The results demonstrate that E2 may play both direct and indirect role in regulation of ET-1 gene expression and production in human endothelial cells. E2-induced increase in NO but decrease in ET-1 production may partly explain the mechanism of the protective effects of the hormone on the cardiovascular system.