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4. A simplified metabolomic analysis of dried blood spots in breast cancer patients.

Author

Thodi, Georgia, Triantopoulou, Aikaterini, Iliou, Aikaterini, Molou, Elina, Dotsikas, Yannis, and Loukas, Yannis L.

Subjects
DRIED blood spot testing, BREAST ultrasound, NEWBORN screening, BREAST cancer, BONFERRONI correction, LIQUID chromatography-mass spectrometry
Abstract

Breast cancer (BC) is among the most commonly diagnosed cancers. Besides mammography, breast ultrasonography and the routinely monitored protein markers, the variations of small molecular metabolites in blood may be of great diagnostic value. This study aimed to quantify specific metabolite markers with potential application in BC detection. The study enrolled 50 participants, 25 BC patients and 25 healthy controls (CTRL). Dried blood spots (DBS) were utilized as biological media and were quantified via a simplified liquid chromatography tandem mass spectrometry (LC-MS/MS) method, used in expanded newborn screening. The targeted metabolomic analysis included 12 amino acids and 32 acylcarnitines. Statistical analysis revealed a significant variation of metabolic profiles between BC patients and CTRL. Among the 44 metabolites, 18 acylcarnitines and 10 amino acids remained significant after Bonferroni correction, showing increase or decrease and enabled classification of BC patients and CTRL. The well-established LC-MS/MS protocol could provide results within few minutes. Therefore, the combination of an easy-to-handle material-DBS and LC-MS/MS protocol could facilitate BC screening/diagnosis and in the next step applied to other cancer patients, as well. [ABSTRACT FROM AUTHOR]

Published
2024
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5. The relationship between neurotransmission-related amino acid blood concentrations and neuropsychological performance following acute exercise.

Author

Parthimos, Theodore P., Schulpis, Kleopatra H., Karousi, Alexandra D., Loukas, Yannis L., and Dotsikas, Yannis

Subjects
TRAIL Making Test, AMINO acid neurotransmitters, NEUROPSYCHOLOGICAL tests, AMINO acids, NERVOUS system
Abstract

Amino acid neurotransmitters, including glutamate, phenylalanine, tyrosine, alanine, and glycine, underlie the majority of the excitatory and inhibitory neurotransmission in the nervous system, and acute exercise has been shown to modulate their concentrations. We aimed to determine whether any correlation exists between the above-mentioned amino acid blood concentrations and the neuropsychological performance after an acute exercise intervention. Sixty basketball players were randomly assigned to one of two experimental conditions: exercise or inactive resting. All participants underwent a comprehensive neuropsychological assessment and blood samples were taken on a Guthrie card before and after the end of the experimental conditions. Amino acid blood concentrations were significantly elevated and cognitive performance significantly improved post-exercise on specific neuropsychological assessments. Significant intervention × group interaction effects were apparent for Trail Making Test part-B [F(1,58) = 20.46, p <.0001, η2 =.26] and Digit Span Backwards [F(1,58) = 15.47, p <.0001, η2 =.21] neuropsychological assessments. Additionally, regression analysis indicated that tyrosine accounted for 38.0% of the variance in the Trail Making Test part-A test. These results suggest that elevated blood concentrations of neurotransmission-related amino acids are associated with improved neuropsychological performance after a single bout of high-intensity exercise. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Homologous Recombination Deficiency Score Determined by Genomic Instability in a Romanian Cohort

Author

Rădoi, Viorica-Elena, primary, Țurcan, Mihaela, additional, Maioru, Ovidiu Virgil, additional, Dan, Andra, additional, Bohîlțea, Laurentiu Camil, additional, Dumitrescu, Elena Adriana, additional, Gheorghe, Adelina Silvana, additional, Stănculeanu, Dana Lucia, additional, Thodi, Georgia, additional, Loukas, Yannis L., additional, and Săbău, Ileana-Delia, additional

Published
2023
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15. Enhanced interpretation of newborn screening results without analyte cutoff values

Author

Marquardt, Gregg, Currier, Robert, McHugh, David M.S., Gavrilov, Dimitar, Magera, Mark J., Matern, Dietrich, Oglesbee, Devin, Raymond, Kimiyo, Rinaldo, Piero, Smith, Emily H., Tortorelli, Silvia, Turgeon, Coleman T., Lorey, Fred, Wilcken, Bridget, Wiley, Veronica, Greed, Lawrence C., Lewis, Barry, Boemer, François, Schoos, Roland, Marie, Sandrine, Vincent, Marie-Françoise, Sica, Yuri Cleverthon, Domingos, Mouseline Torquado, Al-Thihli, Khalid, Sinclair, Graham, Al-Dirbashi, Osama Y., Chakraborty, Pranesh, Dymerski, Mark, Porter, Cory, Manning, Adrienne, Seashore, Margretta R., Quesada, Jonessy, Reuben, Alejandra, Chrastina, Petr, Hornik, Petr, Mandour, Iman Atef, Sharaf, Sahar Abdel Atty, Bodamer, Olaf, Dy, Bonifacio, Torres, Jasmin, Zori, Roberto, Cheillan, David, Vianey-Saban, Christine, Ludvigson, David, Stembridge, Adrya, Bonham, Jim, Downing, Melanie, Dotsikas, Yannis, Loukas, Yannis L., Papakonstantinou, Vagelis, Zacharioudakis, Georgios S.A., Baráth, Ákos, Karg, Eszter, Franzson, Leifur, Jonsson, Jon J., Breen, Nancy N., Lesko, Barbara G., Berberich, Stanton L., Turner, Kimberley, Ruoppolo, Margherita, Scolamiero, Emanuela, Antonozzi, Italo, Carducci, Claudia, Caruso, Ubaldo, Cassanello, Michela, Marca, Giancarlo la, Pasquini, Elisabetta, Di Gangi, Iole Maria, Giordano, Giuseppe, Camilot, Marta, Teofoli, Francesca, Manos, Shawn M., Peterson, Colleen K., Mayfield Gibson, Stephanie K., Sevier, Darrin W., Lee, Soo-Youn, Park, Hyung-Doo, Khneisser, Issam, Browning, Phaidra, Gulamali-Majid, Fizza, Watson, Michael S., Eaton, Roger B., Sahai, Inderneel, Ruiz, Consuelo, Torres, Rosario, Seeterlin, Mary A., Stanley, Eleanor L., Hietala, Amy, McCann, Mark, Campbell, Carlene, Hopkins, Patrick V., de Sain–Van der Velden, Monique G., Elvers, Bert, Morrissey, Mark A., Sunny, Sherlykutty, Knoll, Detlef, Webster, Dianne, Frazier, Dianne M., McClure, Julie D., Sesser, David E., Willis, Sharon A., Rocha, Hugo, Vilarinho, Laura, John, Catharine, Lim, James, Caldwell, S. Graham, Tomashitis, Kathy, Castiñeiras Ramos, Daisy E., de Juan, Jose Angel Cocho, Fernández, Inmaculada Rueda, Macías, Raquel Yahyaoui, Egea-Mellado, José María, González-Gallego, Inmaculada, Pecellin, Carmen Delgado, Bermejo, Maria Sierra García-Valdecasas, Chien, Yin-Hsiu, Hwu, Wuh-Liang, Childs, Thomas, McKeever, Christine D., Tanyalcin, Tijen, Abdulrahman, Mahera, Queijo, Cecilia, Lemes, Aída, Davis, Tim, Hoffman, William, Baker, Mei, and Hoffman, Gary L.

Published
2012
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17. Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project

Author

McHugh, David M.S., Cameron, Cynthia A., Abdenur, Jose E., Abdulrahman, Mahera, Adair, Ona, Al Nuaimi, Shahira Ahmed, Åhlman, Henrik, Allen, Jennifer J., Antonozzi, Italo, Archer, Shaina, Au, Sylvia, Auray-Blais, Christiane, Baker, Mei, Bamforth, Fiona, Beckmann, Kinga, Pino, Gessi Bentz, Berberich, Stanton L., Binard, Robert, Boemer, François, Bonham, Jim, Breen, Nancy N., Bryant, Sandra C., Caggana, Michele, Caldwell, S. Graham, Camilot, Marta, Campbell, Carlene, Carducci, Claudia, Cariappa, Rohit, Carlisle, Clover, Caruso, Ubaldo, Cassanello, Michela, Castilla, Ane Miren, Ramos, Daisy E Castiñeiras, Chakraborty, Pranesh, Chandrasekar, Ram, Ramos, Alfredo Chardon, Cheillan, David, Chien, Yin-Hsiu, Childs, Thomas A., Chrastina, Petr, Sica, Yuri Cleverthon, de Juan, Jose Angel Cocho, Colandre, Maria Elena, Espinoza, Veronica Cornejo, Corso, Gaetano, Currier, Robert, Cyr, Denis, Czuczy, Noemi, D'Apolito, Oceania, Davis, Tim, de Sain-Van der Velden, Monique G., De Pecellin, Carmen lgado, Di Gangi, Iole Maria, Di Stefano, Cristina Maria, Dotsikas, Yannis, Downing, Melanie, Downs, Stephen M., Dy, Bonifacio, Dymerski, Mark, Rueda, Inmaculada, Elvers, Bert, Eaton, Roger, Eckerd, Barbara M., El Mougy, Fatma, Eroh, Sarah, Espada, Mercedes, Evans, Catherine, Fawbush, Sandy, Fijolek, Kristel F., Fisher, Lawrence, Franzson, Leifur, Frazier, Dianne M., Garcia, Luciana R.C., Bermejo, Maria Sierra García-Valdecasas, Gavrilov, Dimitar, Gerace, Rosemarie, Giordano, Giuseppe, Irazabal, Yolanda González, Greed, Lawrence C., Grier, Robert, Grycki, Elyse, Gu, Xuefan, Gulamali-Majid, Fizza, Hagar, Arthur F., Han, Lianshu, Hannon, W. Harry, Haslip, Christa, Hassan, Fayza Abdelhamid, He, Miao, Hietala, Amy, Himstedt, Leslie, Hoffman, Gary L., Hoffman, William, Hoggatt, Philis, Hopkins, Patrick V., Hougaard, David M., Hughes, Kerie, Hunt, Patricia R., Hwu, Wuh-Liang, Hynes, June, Ibarra-González, Isabel, Ingham, Cindy A., Ivanova, Maria, Jacox, Ward B., John, Catharine, Johnson, John P., Jónsson, Jón j, Karg, Eszter, Kasper, David, Klopper, Brenda, Katakouzinos, Dimitris, Khneisser, Issam, Knoll, Detlef, Kobayashi, Hirinori, Koneski, Ronald, Kožich, Viktor, Kouapei, Rasoul, Kohlmueller, Dirk, Kremensky, Ivo, la Marca, Giancarlo, Lavochkin, Marcia, Lee, Soo-Youn, Lehotay, Denis C., Lemes, Aida, Lepage, Joyce, Lesko, Barbara, Lewis, Barry, Lim, Carol, Linard, Sharon, Lindner, Martin, Lloyd-Puryear, Michele A., Lorey, Fred, Loukas, Yannis L., Luedtke, Julie, Maffitt, Neil, Magee, J. Fergall, Manning, Adrienne, Manos, Shawn, Marie, Sandrine, Hadachi, Sônia Marchezi, Marquardt, Gregg, Martin, Stephen J., Matern, Dietrich, Gibson, Stephanie K. Mayfield, Mayne, Philip, McCallister, Tonya D., McCann, Mark, McClure, Julie, McGill, James J., McKeever, Christine D., McNeilly, Barbara, Morrissey, Mark A., Moutsatsou, Paraskevi, Mulcahy, Eleanor A., Nikoloudis, Dimitris, Norgaard-Pedersen, Bent, Oglesbee, Devin, Oltarzewski, Mariusz, Ombrone, Daniela, Ojodu, Jelili, Papakonstantinou, Vagelis, Reoyo, Sherly Pardo, Park, Hyung-Doo, Pasquali, Marzia, Pasquini, Elisabetta, Patel, Pallavi, Pass, Kenneth A., Peterson, Colleen, Pettersen, Rolf D., Pitt, James J., Poh, Sherry, Pollak, Arnold, Porter, Cory, Poston, Philip A., Price, Ricky W., Queijo, Cecilia, Quesada, Jonessy, Randell, Edward, Ranieri, Enzo, Raymond, Kimiyo, Reddic, John E., Reuben, Alejandra, Ricciardi, Charla, Rinaldo, Piero, Rivera, Jeff D., Roberts, Alicia, Rocha, Hugo, Roche, Geraldine, Greenberg, Cheryl Rochman, Mellado, José María Egea, Juan-Fita, María Jesús, Ruiz, Consuelo, Ruoppolo, Margherita, Rutledge, S. Lane, Ryu, Euijung, Saban, Christine, Sahai, Inderneel, García-Blanco, Maria Isabel Salazar, Santiago-Borrero, Pedro, Schenone, Andrea, Schoos, Roland, Schweitzer, Barb, Scott, Patricia, Seashore, Margretta R., Seeterlin, Mary A., Sesser, David E., Sevier, Darrin W., Shone, Scott M., Sinclair, Graham, Skrinska, Victor A., Stanley, Eleanor L., Strovel, Erin T., Jones, April L Studinski, Sunny, Sherlykutty, Takats, Zoltan, Tanyalcin, Tijen, Teofoli, Francesca, Thompson, J. Robert, Tomashitis, Kathy, Domingos, Mouseline Torquado, Torres, Jasmin, Torres, Rosario, Tortorelli, Silvia, Turi, Sandor, Turner, Kimberley, Tzanakos, Nick, Valiente, Alf G., Vallance, Hillary, Vela-Amieva, Marcela, Vilarinho, Laura, von Döbeln, Ulrika, Vincent, Marie-Francoise, Vorster, B. Chris, Watson, Michael S., Webster, Dianne, Weiss, Sheila, Wilcken, Bridget, Wiley, Veronica, Williams, Sharon K., Willis, Sharon A., Woontner, Michael, Wright, Katherine, Yahyaoui, Raquel, Yamaguchi, Seiji, Yssel, Melissa, and Zakowicz, Wendy M.

Published
2011
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23. Quantitation and evaluation of perinatal medium-chain and long-chain acylcarnitine blood concentrations in 12,000 full-term breastfed newborns

Author

Manta-Vogli, Penelope D. Schulpis, Kleopatra H. Loukas, Yannis L. Dotsikas, Yannis

Abstract

Objectives: Medium-chain (MCA) and long-chain acylcarnitine (LCA) blood concentrations play a significant role in the fatty acid (FA) oxidation process, especially during the first days of life. Identification of their abnormal concentrations, via expanded newborn screening, can lead to the diagnosis of FA oxidation disorders. This study aimed to demonstrate MCA and LCA concentrations in Dried Blood Spots (DBS) of full-term breastfed infants, in relation to their birth weight (BW) perinatally. Methods: Breastfed full-term infants (n = 12,000, 6,000 males, 6,000 females) with BW 2,000-3,999 g were divided into four equal groups: Group A, 2,000-2,499 g, B 2,500-2,999 g, C 3,000-3,499 g, and D 3,500-3,999 g. Samples were collected as DBS and acylcarnitines were determined via a liquid chromatography tandem mass spectrometry method. Results: MCA and LCA blood concentrations were determined significantly lower in group A (low birth weight infants) in both sexes. Infants with BW > 3,500 g (group D), were characterized by lower levels of C10, C10:1, C14, C14:1 acylcarnitines and higher levels of C16 and C18:1 acylcarnitines, as compared to the other groups of this study. Conclusions: Concentration patterns in full-term breastfed newborns in relation to sex and mainly BW found in this study could be very helpful for neonatologists, especially for newborns of group A.

Published
2021

25. Perinatal Reduced Blood Concentrations of Free Carnitine and Acylcarnitines in Infants with Cystic Fibrosis

Author

Schulpis, Kleopatra H. Molou, Elina Manta-Vogli, Penelope and Dotsikas, Yannis Thodi, Georgia Chatzidaki, Maria Loukas, Yannis L. and Schulpis, Kleopatra H. Molou, Elina Manta-Vogli, Penelope and Dotsikas, Yannis Thodi, Georgia Chatzidaki, Maria Loukas, Yannis L.

Abstract

Objective Cystic fibrosis (CF) is a multisystemic inherited disease. The aim of this study was to determine free carnitine (FC) and acylcarnitine concentrations in CF newborns with various mutations of the CFTR gene perinatally. Study Design FC/acylcarnitines were determined in dried blood spots via liquid chromatography-tandem mass spectrometry (LC-MS/MS) on the third day of life of full-term normal ( n =50) and CF ( n =28) newborns. For infants with elevated immunoreactive trypsinogen values, FC/acylcarnitines were quantified again 48hours later, followed by mutational analysis of CFTR gene via Sanger sequencing. Results Initial FC and sums of acylcarnitine concentrations were statistically significantly lower in CF patients than in controls and even lower 48hours later. The mutations F508del and 621+1G>T were predominantly identified among CF patients. Conclusion Low FC and acylcarnitine concentrations were measured perinatally in CF patients, for all CFTR mutations detected. Carnitine supplementation of breastfeeding mothers could be beneficial.

Published
2021

38. Understanding molecular association and isomers recognition in isomer-cyclodextrin multiple complex formation by improved liquid chromatographic studies

Author

Loukas, Yannis L.

Subjects
Cyclodextrins -- Analysis, Liquid chromatography -- Usage, Isomerization -- Analysis, Chemical bonds -- Analysis, Chemistry
Abstract

Equations are derived that allow the determination of guest-cyclodextrin primary ([K.sub.11]), secondary ([K.sub.12]), and higher order ([K.sub.1n]) binding constants as well as the degree of complexation n (the percent of complexed guest), by monitoring the observed capacity factor [k[prime].sub.obs] for guests that can be structural, geometric, or optical isomers. The retention behavior (elution order) in a mixture of isomers is dependent on the cyclodextrin concentration in the mobile phase as well as on the stoichiometry and the binding constant of the guest-cyclodextrin (G-CD) complex. The simplification of higher order complexes (G C[D.sub.n]) to that with 1:1 stoichiometry can lead to erroneous results; therefore, it is important for the stoichiometry to be determined accurately, prior to any binding constant calculations, following the continuous variation method. The proposed models are solved iteratively using nonlinear least-squares analysis and following specific algorithms.

Published
1998

46. Perinatal Reduced Blood Concentrations of Free Carnitine and Acylcarnitines in Infants with Cystic Fibrosis.

Author

Schulpis, Kleopatra H., Molou, Elina, Manta-Vogli, Penelope, Dotsikas, Yannis, Thodi, Georgia, Chatzidaki, Maria, and Loukas, Yannis L.

Subjects
NEWBORN screening, CARNITINE, GENETIC mutation, SEQUENCE analysis, LIQUID chromatography, CYSTIC fibrosis, T-test (Statistics), ACYLTRANSFERASES, MASS spectrometry, DESCRIPTIVE statistics, DATA analysis software, FATTY acids, CHILDREN
Abstract

Objective  Cystic fibrosis (CF) is a multisystemic inherited disease. The aim of this study was to determine free carnitine (FC) and acylcarnitine concentrations in CF newborns with various mutations of the CFTR gene perinatally. Study Design  FC/acylcarnitines were determined in dried blood spots via liquid chromatography-tandem mass spectrometry (LC-MS/MS) on the third day of life of full-term normal (n  = 50) and CF (n  = 28) newborns. For infants with elevated immunoreactive trypsinogen values, FC/acylcarnitines were quantified again 48 hours later, followed by mutational analysis of CFTR gene via Sanger sequencing. Results  Initial FC and sums of acylcarnitine concentrations were statistically significantly lower in CF patients than in controls and even lower 48 hours later. The mutations F508del and 621 + 1G > T were predominantly identified among CF patients. Conclusion  Low FC and acylcarnitine concentrations were measured perinatally in CF patients, for all CFTR mutations detected. Carnitine supplementation of breastfeeding mothers could be beneficial. [ABSTRACT FROM AUTHOR]

Published
2021
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50. The phenylketonuria patient: A recent dietetic therapeutic approach.

Author

Manta-Vogli, Penelope D., Dotsikas, Yannis, Loukas, Yannis L., and Schulpis, Kleopatra H.

Subjects
ELEMENTAL diet, AMINO acids, INTELLECTUAL disabilities, SEIZURES (Medicine), EARLY diagnosis
Abstract

Phenylalanine hydroxylase (PAH) deficiency, commonly named phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism inherited with an autosomal recessive trait. It is characterized by high blood and cerebral Phe levels, resulting in intellectual disabilities, seizures, etc. Early diagnosis and treatment of the patients prevent major neuro-cognitive deficits. Treatment consists of a lifelong restriction of Phe intake, combined with the supplementation of special medical foods, such as Amino Acid medical food (AA-mf), enriched in tyrosine (Tyr) and other amino acids and nutrients to avoid nutritional deficits. Developmental and neurocognitive outcomes for patients, however, remain suboptimal, especially when adherence to the demanding diet is poor. Additions to treatment include new, more palatable foods, based on Glycomacropeptide that contains limited amounts of Phe, the administration of large neutral amino acids to prevent phenylalanine entry into the brain and tetrahydrobiopterin cofactor capable of increasing residual PAH activity. Moreover, further efforts are underway to develop an oral therapy containing phenylalanine ammonia-lyase. Nutritional support of PKU future mothers (maternal PKU) is also discussed. This review aims to summarize the current literature on new PKU treatment strategies. [ABSTRACT FROM AUTHOR]

Published
2020
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