Artículos científicos

http://www.ncbi.nlm.nih.gov/pubmed?term=acu%C3%B1a%20castroviejo%20d

http://www.ncbi.nlm.nih.gov/pubmed?term=escames%20g

1. Acuña-Castroviejo D. Regulacion postural del sistema renina-angiotensina-aldosterona. Efectos de la depleccion del volumen circulante efectivo y de la actividad simpática. Laboratorio 1977; 65:501-518.

2. Acuña-Castroviejo D, Garcia del Rio C, Alba F, Sánchez-Cantalejo E, Osorio C, Quesada T. Efectos del cambio postural y de la depleción de volumen sobre el sistema renina-angiotensina-aldosterona. Rev Esp Fisiol 1978; 34:411-416. PMDI: 741062.

3. Alba F, Garcia del Rio C, Acuña-Castroviejo D, Soler A, García-Torres L, Quesada T. Effect of sodium and osmolarity on renin secretion. Rev Esp Fisiol 1978; 35:433-436. PMDI: 396613.

4. Noguera M, Garcia del Rio C, Acuña-Castroviejo D, Soler A, Quesada T. Efecto del propanolol sobre la APR en ratas hipovolemicas. Laboratorio 1979; 68:501-506.

5. Garcia del Rio C, Acuña-Castroviejo D, Alba F, Garcia-Torres L, Osorio C, Quesada T. The effect of orthostathism, passive tilting and recumbent exercice on renin release. Rev Esp Fisiol 1980; 36:237-242. PMDI: 7001580.

6. Acuña-Castroviejo D, García-Torres L, Vargas F, Soler A, Sánchez-Cantalejo E, Garcia del Rio C. Papel de la glándula pineal en la función suprarrenal de ratas ovariectomizadas. Laboratorio 1981; 72:207-216.

7. Acuña-Castroviejo D, Soler A, García-Torres L, Vargas F, Garcia del Rio C, Quesada T, Osorio C. Inhibition of the renin-angiotensin system by pinealectomy in female rats. Rev Esp Fisiol 1982; 38:251-256. PMDI: 6760267.

8. Acuña-Castroviejo D, Alba F, Garcia-Torres L, Soler A, Vargas F, Garcia del Rio C. Calcium and renin release: inhibition of low-sodium-induced renin secretion by high calcium concentration in rat kidney perfusion. Rev Esp Fisiol 1982; 38:167-170. PMDI: 6750722.

9. Garcia del Rio C, Garcia-Torres L, Soler A, Vargas F, Acuña-Castroviejo D. Hormona antidiurética.I. Biosíntesis, metabolismo y métodos de medida. Laboratorio 1982; 74:379-405.

10. Garcia del Rio C, Acuña-Castroviejo D, Bustamante M, Soler A, Garcia-Torres L, Osorio C. Increased activity of the renin angiotensin system during the perinatal period. Rev Esp Fisiol 1982; 38:171-176. PMDI: 6750723.

11. Acuña-Castroviejo D, Garcia del Rio C, García-Torres L, Luna J, Osorio C. Role of pineal gland in kidney-adrenal homeostasis. Horm Metab Res 1983; 16:589-592. PMDI: 6096245.

12. Del Rosal JA, Moral MJ, Fernández MA, Abril MJ, Quesada G, Acuña-Castroviejo D. Influencia de la glándula pineal sobre los niveles de prolactina y hormona luteopra en ratas hembra. Laboratorio 1985; 80:271-279.

13. Acuña-Castroviejo D, Lowenstein PR, Rosenstein RE, Cardinali DP. Diurnal variations of benzodiapine binding in rat cerebral cortex: disruption by pinealectomy. J Pineal Res 1986; 3:101-109. PMDI: 3014109.

14. Acuña-Castroviejo D, Romero HE, Cardinali DP. Changes in gamma-aminobutiryc acid hight affinity binding to cerebral cortex membranes after pinealectomy or melatonin administrations to rats. Neuroendocrinology 1986; 43:24-31. PMDI: 3713987.

15. Cardinali DP, Lowenstein PR, Rosenstein RE, González Solveyra C, Sarmiento MI, Romero HE, Acuña-Castroviejo D. Functional links between benzodiazepine and GABA receptors and pineal activity. Adv Biochem Psychopharmacol 1986; 42:155-164. PMDI: 3020894.

16. Fernández B, Malde JL, Montero A, Acuña-Castroviejo D. Pineal gland and gonadotropins: Renal clearence rate of FSH, LH and melatonin in the fertile period and in peri- and postmenopausal women. Med Sci Res 1988; 16:849-850.

17. Acuña-Castroviejo D, Vargas F, Castillo MA, Haro JM, Garcia-Torres L. Effects of selective and non selective 1-blockade on renin secretion in the isolated rat kidney. Rev Esp Fisiol 1989; 45:195-198. PMDI: 2570449.

18. Acuña-Castroviejo D, Fernández B, Del Aguila CM, Castillo JL. Lesions in suprachiasmatic nuclei simulate effects of pinealectomy on prolactin release in ovariectomized and sulpiride-treated female rats. Experientia 1989; 45:739-742. PMDI: 2759205.

19. Castillo JL, Del Aguila CM, Acuña-Castroviejo D. La Glándula pineal en el niño. I. Aspectos morfofuncionales y bioquímicos. Bol Pediat 1989; 30:107-117.

20. Del Aguila CM, Castillo JL, Acuña-Castroviejo D. La Glándula pineal en el niño. II. Mecanismos de regulación y función neuroendocrina. Fisiopatología tumoral. Bol Pediat 1989; 30:191-203.

21. Acuña-Castroviejo D, Fernández B, Gomar MD, Del Aguila CM, Castillo JL. Influence of the pituitary-adrenal axis on benzodiazepine receptor binding to rat cerebral cortex. Neuroendocrinology 1990; 51:97-103. PMDI: 2154713.

22. Fernández B, Montero A, Malde JL, Acuña-Castroviejo D. Relationship between renal clearance rates and plasma levels of FSH, hCG, DHAs and melatonin during normal pregnancy. Med Sci Res 1990; 18:713-714. PMDI:2308340.

23. Fernández B, Malde JL, Montero A, Acuña-Castroviejo D. Relationships between adenohypophyseal and steroid hormones and variations in serum and urinary melatonin levels during the ovarian cycle, perimenopause and menopause in healthy women. J Steroid Biochem Mol Med 1990; 35:257-262. PMDI: 2308340.

24. López Escámez JA, Delgado Martín AE, Del Aguila CM, Castillo JL, Acuña-Castroviejo D. Estudio morfométrico del parénquima de la glándula pineal. Posible división en zona cortical y medular. Cienc Med 1990; 7:25-30.

25. Acuña-Castroviejo D, Del Aguila CM, Fernández B, Gomar MD, Castillo JL. Pinealectomy increases ouabain high-affinity binding sites and dissociation constant in rat cerebral cortex. Neurosci Lett 1991; 127:227-230. PMDI: 1652717.

26. Acuña-Castroviejo D, Castillo JL, Fernández B, Gomar MD, Del Aguila CM. Modulation by pineal gland of ouabain high-affinity binding sites in rat pineal gland. Am J Physiol 1992; 262:R698-R706. PMDI: 1314517.

27. Acuña-Castroviejo D, Del Aguila CM, Fernández B, Gomar MD, Castillo JL. Characterization of ouabain high affinity binding to rat cerebral cortex. Modulation by melatonin. Eur J Pharmacol 1992; 226:59-67. PMDI: 1397056.

28. Castillo JL, Vives F, Acuña-Castroviejo D. Paradoxical effects of melatonin on spontaneous neuronal activity in the striatum of sham-operated and pinealectomized rats. J Pineal Res 1992; 12:149-154. PMDI: 1403608.

29. Fernández B, Montero A, Del Aguila CM, Malde JL, Castillo JL, Acuña-Castroviejo D. Relationship between pineal activity and the hypotalamus-hypophysis-gonadal axis in human pregnancy and in the cord blood of term Infants. II. Melatonin and protein hormones. Steroid Biochem (Life Sci Adv ) 1992; 11:97-103.

30. Fernández B, Malde JL, Castillo JL, Montero A, Del Aguila CM, Acuña-Castroviejo D. Relationship between pineal activity and the hypotalamus-hypophysis-gonadal axis in human pregnancy and in the cord blood of term infants. I. Melatonin and steroid hormones. Steroid Biochem (Life Sci Adv ) 1992; 11:89-96.

31. Muñoz A, Rodríguez T, Molina A, Martínez JJ, Ruiz C, Acuña-Castroviejo D. Melatonin concentration in the umbilical artery and vein in human preterm and term neonates and neonates with acute fetal distress. J Pineal Res 1992; 13:184-191. PMDI: 1287194.

32. Acuña-Castroviejo D, Fernández B, Castillo JL, Del Aguila CM. Similarity between the effects of suprachiasmatic nuclei lesions and of pinealectomy on gonadotropin release in ovariectomized and sulpiride-treated female rats. Experientia 1993; 49:797-801. PMDI: 8405305.

33. Acuña-Castroviejo D, Pablos M, Menéndez Peláez A, Reiter RJ. Melatonin receptors in purified cell nuclei of liver. Res Comm Chem Pathol Pharmacol 1993; 82:253-256. PMDI: 8303096.

34. Castillo JL, Vives F, Reiter RJ, Acuña-Castroviejo D. Pineal modulation of the rat caudate-putamen spontaneous neuronal activity: Roles of melatonin and vasotocin. J Pineal Res 1993; 15:147-152. PMDI: 8106961.

35. Fernández B, Del Aguila CM, Castillo JL, Montero A, Malde JL, Acuña-Castroviejo D. Urinary excretion of melatonin and steroid metabolites during normal pregnancy. Med Sci Res 1993; 21:43-45.

36. Gomar MD, Fernández B, Castillo JL, Del Aguila CM, Acuña-Castroviejo D. Melatonin counteracts pinealectomy-dependent decreases in rat brain [3H] flunitrazepam binding through an opioid mechanism. Neurosci Lett 1993; 164:149-153. PMDI: 8152592.

37. Gomar MD, Castillo JL, Del Aguila CM, Fernández B, Acuña-Castroviejo D. Intracerebroventricular injection of naloxone blocks melatonin- dependent brain [3H] flunitrazepam binding. NeuroReport 1993; 4:987-990. PMDI: 8396464.

38. Gomar MD, Fernández B, Castillo JL, Del Aguila CM, Acuña-Castroviejo D. Suppressive effect of simultaneous injection of ACTH1-10 and beta-endorphin on brain [3H] flunitrazepam binding. NeuroReport 1993; 5:252-254. PMDI: 8298084.

39. Jaldo Alba F, Muñoz-Hoyos A, Molina-Carballo A, Molina Font JA, Acuña-Castroviejo D. Light deprivation increases plasma levels of melatonin during the first 72 h of life in human infants. Acta Endocrinol 1993; 129:442-445. PMDI: 8279225.

40. Muñoz-Hoyos A, Jaldo Alba F, Molina-Carballo A, Rodríguez Cabezas T, Molina Font JA, Acuña-Castroviejo D. Absence of plasma melatonin circadian rhythm during the first 72 hours of life human infants. J Clin Endocrinol Metab 1993; 77:699-703. PMDI: 8370692.

41. Acuña-Castroviejo D, Russel J.Reiter, Menéndez Peláez A, Pablos MI, Burgos A. Characterization of high-affinity melatonin binding sites in purified cell nuclei of rat liver. J Pineal Res 1994; 16:100-112. PMDI: 8014823.

42. Gomar MD, Fernández B, Del Aguila CM, Castillo JL, de Dios-Luna J., Acuña-Castroviejo D. Influence of the behaviorally active peptides ACTH1-10 and ACTH4-10 on the melatonin modulation of 3H-flunitrazepam receptor binding in the rat cerebral cortex. Neuroendocrinology 1994; 60:252-260. PMDI: 7969783.

43. Molina-Carballo A, Acuña-Castroviejo D, Rodriguez-Cabezas T, Muñoz-Hoyos A. Effects of febrile and epileptic convulsions on daily variations in plasma melatonin concentration in children. J Pineal Res 1994; 16:1-9. PMDI: 8158517.

44. Molina-Carballo A, Muñoz-Hoyos A, Rodríguez Cabezas T, Acuña-Castroviejo D. Day-night variations in melatonin secretion by the pineal gland during febrile and epileptic convulsions in children. Psychiat Res 1994; 52:273-283. PMDI: 7991721.

45. Acuña-Castroviejo D, Escames G, Macías M, Muñoz-Hoyos A, Molina-Carballo A, Arauzo M, Montes R, Vives F. Cell protective role of melatonin in the brain. J Pineal Res 1995; 19:57-63. PMDI: 8609597.

46. Castillo Romero JL, Acuña-Castroviejo D, Escames G, Vives F. Age-related changes of neuronal responsiveness to melatonin in the striatum of sham-operated and pinealectomized rats. J Pineal Res 1995; 19:79-86. PMDI: 8609600.

47. Gomar MD, Fernández B, Del Aguila CM, Castillo JL, Escames G, Acuña-Castroviejo D. Participation of ACTH1-10 and ACTH4-10 on the melatonin modulation of benzodiazepine receptors in rat cerebral cortex. Experientia 1995; 51:209-212. PMDI: 7698280.

48. Pablos MI, Agapito MT, Gutierrez R, Recio JM, Reiter RJ, Barlow-Walden L, Acuña-Castroviejo D, Menéndez Peláez A. Melatonin stimulates the activity of the detoxifying enzyme glutathione peroxidase in several tissues of chicks. J Pineal Res 1995; 19:111-115. PMDI: 8750343.

49. Reiter RJ, Melchiorri D, Sewerynek E, Poeggeler B, Barlow-Walden L, Chuang J, Ortiz GG, Acuña-Castroviejo D. A review of the evidence supporting melatonin's role as an antioxidant. J Pineal Res 1995; 18:1-11. PMDI: 7776173.

50. Acuña-Castroviejo D, Macías M, Crespo E, Arauzo M, León J, Martín M, Escames G, Vives F. Potenciales efectos de la melatonina en el envejecimiento. Rev Soc Esp Med Est 1996; 41:8-19.

51. Bettahi I, Pozo D, Osuna C, Reiter RJ, Acuña-Castroviejo D, Guerrero JM. Melatonin reduces nitric oxide synthase activity in rat hypothalamus. J Pineal Res 1996; 20:205-210. PMDI: 2308340.

52. Escames G, Acuña-Castroviejo D, Vives F. Melatonin-dopamine interaction in the striatal projection area of sensorimotor cortex in the rat. NeuroReport 1996; 7: 597-600. PMDI: 8730838.

53. Molina-Carballo A, Muñoz-Hoyos A, Martin-Garcia JA, Uberos-Fernández J, Rodriguez-Cabezas T, Acuña-Castroviejo D. 5-Methoxytryptophol and melatonin in children: differences due to age and sex. J Pineal Res 1996; 21:73-79. PMDI: 8912232.

54. Molina CA, Muñoz-Hoyos A, Uberos-Fernández J, Acuña-Castroviejo D, Molina Font JA. Funcionalismo pineal (tasas de melatonin) en niños sanos de diferentes edades. Actualidad e interés del estudio de la glánduyla pineal en Pediatría. An Esp Pediat 1996; 45:33-44. PMDI: 8849128.

55. Muñoz-Hoyos A, Amorós-Rodriguez I, Molina-Carballo A, Uberos-Fernández J, Acuña-Castroviejo D. Pineal response after pyridoxine test in children. J Neural Transm 1996; 103:833-842. PMDI: 8872867.

56. Pablos MI, Agapito MT, Menéndez Peláez A, Acuña-Castroviejo D, Reiter RJ, Recio JM. Iron decreases the nuclear but not the cytosolic content of the neurohormone melatonin in several tissues in chicks. J Cell Biochem 1996; 60:317-321. PMDI: 8867807.

57. Salmerón JM, Escames G, Pérez-Jaranay JM, Vives Montero F. Electrophysiological response of neurons of the mediodorsal nucleus of the thalamus to the stimulation of the nucleus accumbens in the rat. Neurosci Res Comm 1996; 19:109-114.

58. Acuña-Castroviejo D, Coto-Montes A, Gaia Monti M, Ortiz GG, Reiter RJ. Melatonin is protective against MPTP-induced striatal and hyppocampal lesions. Life Sci 1997; 60:PL23-PL29. PMDI: 9000122.

59. Crespo E, Macías M, Martín M, Arauzo M, León J, Escames G, Acuña-Castroviejo D. Mecanismos de neuroprotección de la melatonina durante el envejecimiento. Arch Neuroci 1997; 2:247-257.

60. Escames G, Guerrero JM, Reiter RJ, García JJ, Muñoz A, Ortiz GG, Oh CS. Melatonin and vitamin E prevent nitric oxide-induced lipid peroxidation in rat brain homogenates. Neurosci Lett 1997; 230:147-150. PMDI:927682.

61. García JJ, Reiter RJ, Guerrero JM, Escames G, Yu BP, Oh CS, Muñoz-Hoyos A. Melatonin prevents changes in microsomal membrane fluidity during induced lipid peroxidation. FEBS Lett 1997; 408:297-300. PMDI: 9188780.

62. Molina-Carballo A, Muñoz-Hoyos A, Reiter RJ, Sánchez-Forte M, Moreno-Madrid F, Rufo-Campos M, Molina-Carballo A, Acuña-Castroviejo D. Utility of hogh doses of melatonin as adjuntive anticonvulsant therapy in a child with severe myoclonic epilepsy: two years' experience. J Pineal Res 1997; 23:97-105. PMDI: 9392448.

63. Muñoz-Hoyos A, Molina-Carballo A, Escames G, García JJ, Ortiz GG, Molina Font JA. Glándula pineal y patología infantil: Interés clínico y perspectivas futuras. Arch Neuroci 1997; 2:258-268.

64. Muñoz-Hoyos A, Molina-Carballo A, Rodríguez Cabezas T, Uberos-Fernández J, Ruiz Cosano JA, Acuña-Castroviejo D. Relationships between methoxyindole and kynurenine pathway metabolites in plasma and urine in children suffering from febrile and epileptic seizures. Clin Endocrinol 1997; 47:667-677. PMDI: 9497873.

65. Reina AJ, Lopez-Cantarero M, Gallardo A, Fuentes O, Gaitán D, Garcia A, Gonzalez C, Acuña-Castroviejo D. Time-dependent changes of serum gastrin and gastrin receptors in the rat oxyntic mucosa after proximal gastric vagotomy. J Surg Res 1997; 67:186-192. PMDI: 9073566.

66. Reiter RJ, Guerrero JM, Escames G, Papolla MA, Acuña-Castroviejo D. Prophylactic actions of melatonin in oxidative neurotoxicity. Ann N Y Acad Sci 1997; 825:70-78. PMDI: 9369975.

67. Sánchez-Forte M, Moreno-Madrid F, Muñoz-Hoyos A, Molina-Carballo A, Acuña-Castroviejo D, Molina-Font JA. Efecto de la melatonina como anticonvulsivante y protector neuronal. Rev Neurol 1997; 25:1229-1234. PMDI: 9340157.

68. Escames G, Acuña-Castroviejo D, León J, Vives F. Melatonin interaction with magnesium and zinc in the response of the striatum to sensorimotor cortical stimulation in the rat. J Pineal Res 1998; 24:123-129. PMDI: 9580111.

69. García JJ, Reiter RJ, Ortiz GG, Oh CS, Tang L, Yu BP, Escames G. Melatonin enhances tamoxifen's ability to prevent the reduction in microsomal membrane fluidity induced by lipid peroxidation. J Membrane Biol 1998; 162:59-65. PMDI: 9516238.

70. León J, Vives F, Gómez I, Camacho E, Gallo MA, Espinosa A, Escames G, Acuña-Castroviejo D. Modulation of rat striatal glutamatergic response in search for new neuroprotective agents: evaluation of melatonin and some kynurenine derivatives. Brain Res Bull 1998; 45:525-530. PMDI: 9580387.

71. León J, Vives F, Crespo E, Camacho E, Espinosa A, Gallardo A, Escames G, Acuña-Castroviejo D. Modification of nitric oxide synthase activity and neuronal response in rat estriatum by melatonin and kynurenine derivatives. J Neuroendocrinol 1998; 10:297-302. PMDI: 9630400.

72. Muñoz-Hoyos A, Sánchez-Forte M, Molina-Carballo A, Escames G, Martin-Medina E, Reiter RJ, Molina-Font JA, Acuña-Castroviejo D. Melatonin's role as an anticonvulsant and neuronal protector: Experimental and clinical evidence. J Child Neurol 1998; 13:501-509. PMDI: 9796757.

73. Muñoz-Hoyos A, Molina-Carballo A, Macías M, Rodriguez-Cabezas T, Martin-Medina E, Narbona-Lopez E, Valenzuela-Ruiz A, Acuña-Castroviejo D. Comparison between tryptophan methoxyindole and kynurenine metabolic pathway in normal and preterm neonates and in neonates with acute fetal distress. Eur J Endocrinol 1998; 139:89-95. PMDI: 9703384.

74. Reiter RJ, Guerrero JM, García JJ, Acuña-Castroviejo D. Reactive oxygen intermediates, molecular damage and aging: Relation to melatonin. Ann N Y Acad Sci 1998; 854:410-424. PMDI: 9928448.

75. Crespo E, Macías M, Pozo D, Escames G, Martín M, Vives F, Guerrero JM, Acuña-Castroviejo D. Melatonin inhibits expression of the inducible NO synthase II in liver and lung and prevents endotoxemia in lipopolysaccharide-induced multiple organ dysfunction syndrome in rats. FASEB J 1999; 13:1537-1546. PMDI: 10463945.

76. García JJ, Reiter RJ, Pié J, Ortiz GG, Cabrera J, Sainz RM, Acuña-Castroviejo D. Role of pinoline and melatonin in stabilizinmg hepatic microsomal membranes against oxidative stress. J Bioenerg Biomembr 1999; 31:609-616. PMDI: 10281918.

77. Macías M, Rodriguez Cabezas MN, Reiter RJ, Osuna A, Acuña-Castroviejo D. Presence and effects of melatonin in Trypanosome cruzi. J Pineal Res 1999; 27:86-94. PMDI: 10496144.

78. Salvatierra J, Escames G, Hernandez P, Cantero J, Crespo E, León J, Salvatierra D, Acuña-Castroviejo D, Vives F. Cartilage and serum levels of nitric oxide in patients with hip osteoarthritis. J Rheumatol 1999; 26:2015-2017. PMDI: 10493684.

79. García JJ, Reiter RJ, Cabrera JJ, Pié J, Sainz RM, Tan DX, Qi W, Acuña-Castroviejo D. 5-methoxytryptophol preserves hepatic microsomal membrane fluidity during oxidative stress. J Cell Biochem 2000; 76:651-657. PMDI: 10653984.

80. García JJ, Martinez-Ballarin E, Robinson M, Allúe JL, Reiter RJ, Osuna C, Acuña-Castroviejo D. Protective effect of -carbolines and other antioxidants on lipid peroxidation due to hydrogen peroxide in rat brain homogenates. Neurosci Lett 2000; 294:1-4. PMDI: 11044572.

81. Khaldy H, Escames G, León J, Vives F, Luna J, Acuña-Castroviejo D. Comparative effects of melatonin, L-deprenyl, Trolox and ascorbate in the suppression of hydroxyl radical formation during dopamine autoxidation in vitro. J Pineal Res 2000; 2:100-107. PMDI: 10981823.

82. León J, Macías M, Escames G, Camacho E, Khaldy H, Martín M, Espinosa A, Gallo MA, Acuña-Castroviejo D. Structure-related inhibition of calmodulin-dependent nNOS activity by melatonin and synthetic kynurenines. Mol Pharmacol 2000; 58:967-975. PMDI: 11040043.

83. Martín M, Macías M, Escames G, León J, Acuña-Castroviejo D. Melatonin but not vitamins C and E maintains glutathione homeostasis in t-butyl hydroperoxide-induced mitochondrial oxidative stress. FASEB J 2000; 14:1677-1679. PMDI: 10973915.

84. Martín M, Macías M, Escames G, Reiter RJ, Agapito MT, Ortiz GG, Acuña-Castroviejo D. Melatonin-induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo. J Pineal Res 2000; 28:242-248. PMDI: 10831160.

85. Moreno-Madrid F, Muñoz-Hoyos A, Sánchez-Forte M, Molina-Carballo A, Macías González M, Escames Rosa G, Narbona E, Acuña-Castroviejo D. Valoración de un test de función pineal con L-triptófano. Invest Clín 2000; 297-303.

86. Muñoz-Hoyos A, Fernández-García JM, Molina-Carballo A, Macías M, Escames G, Ruiz Cosano C, Acuña-Castroviejo D. Effect of clonidine on plama ACTH, cortisol and melatonin in children. J Pineal Res 2000; 29:48-53. PMDI: 10949540.

87. Reiter RJ, Tan DX, Acuña-Castroviejo D, Burkhardt S, Karbownik M. Melatonin: Mechanisms and actions as an antioxidant. Curr Top Biophys 2000; 24:171-183.

88. Acuña-Castroviejo D, Martín M, Macías M, Escames G, León J, Khaldy H, Reiter RJ. Melatonin, mitochondria and cellular bioenergetics. J Pineal Res 2001; 30:65-74. PMDI: 11270481.

89. Escames G, Macías M, León J, García JJ, Khaldy H, Martín M, Vives F, Acuña-Castroviejo D. Calcium-dependent effects of melatonin inhibition of glutamatergic response in rat striatum. J Neuroendocrinol 2001; 13:459-466. PMDI: 11328457.

90. García JJ, Reiter RJ, Karbownik M, Calvo JR, Ortiz GG, Tan DX, Martinez-Ballarin E, Acuña-Castroviejo D. N-acetyl-serotonin supresses hepatic microsomal membrane rigidity associated with lipid peroxidation. Eur J Pharmacol 2001; 428:169-175. PMDI: 11675033.

91. Girón-Caro F, Muñoz-Hoyos A, Ruiz Cosano C, Bonillo-Perales A, Molina-Carballo A, Escames G, Macías M, Acuña-Castroviejo D. Melatonin and -endorphin changes in children sensitized to olive and grass pollen after treatment with specific immunotherapy. Int Arch Allergy Immunol 2001; 126:91-96. PMDI: 11641610.

92. Muñoz-Hoyos A, Hubber E, Escames G, Molina-Carballo A, Macías M, Valenzuela-Ruiz A, Fernández-García JM, Acuña-Castroviejo D. Effect of propranolol plus exercise on melatonin and GH levels in children with growth delay. J Pineal Res 2001; 30:75-81. PMDI: 11270482.

93. Muñoz-Hoyos A, Jaldo R, Molina-Carballo A, Escames G, Macías M, Fernández-García JM, Reiter RJ, Acuña-Castroviejo D. Characterization of nocturnal ultradian rhythms of melatonin in children with growth hormone-dependent and independent growth delay. J Clin Endocrinol Metab 2001; 86:1181-1187. PMDI: 11238506.

94. Ortiz GG, Crespo López E, Morán-Moguel C, García JJ, Reiter RJ, Acuña-Castroviejo D. Protective role of melatonin against MPTP-induced mouse brain cell DNA fragmentation and apoptosis in vivo. Neuroendocrinol Lett 2001; 22:101-108. PMDI: 11335886.

95. Reiter RJ, Acuña-Castroviejo D, Tan DX, Burkhardt S. Free radical-mediated molecular damage: Mechanisms of melatonin's protective actions in the central nervous system. Ann N Y Acad Sci 2001; 939:200-215. PMDI: 11462772.

96. Acuña-Castroviejo D, Escames G, Carazo A, León J, Khaldy H, Reiter RJ. Melatonin, mitochondrial homeostasis and mitochondrial-related diseases. Curr Top Med Chem 2002; 2:133-151. PMDI: 11899097.

97. Camacho E, León J, Carrión MD, Entrena A, Escames G, Khaldy H, Acuña-Castroviejo D, Gallo MA, Espinosa A. Inhibition of nNOS activity in rat brain by synthetic kynurenines: Structure-activity dependence. J Med Chem 2002; 45:263-274. PMDI: 11784131.

98. Khaldy H, León J, Escames G, Martín M, Macías M, Acuña-Castroviejo D. Circadian rhythm of dopamine and their metabolites in mouse striatum: Effects of pinealectomy and melatonin replacement. Neuroendocrinology 2002; 75:201-208. PMDI: 11914592.

99. Martín M, Macías M, León J, Escames G, Khaldy H, Acuña-Castroviejo D. Melatonin increases the activity of the complexes I and IV of the electron transport chain and the ATP production in rat brain and liver mitochondria. Int J Biochem Cell Biol 2002; 34:348-357. PMDI: 11854034.

100. Muñoz-Hoyos A, Girón F, Ruiz Cosano C, Macías M, Escames G, García JJ, Bonillo A, Molina-Carballo A, Acuña-Castroviejo D. Evaluation of plasma levels of melatonin after midazolam or sodium thiopental anesthesia in children. J Pineal Res 2002; 32:253-256. PMDI: 11982795.

101. Ortega-Gutiérrez S, García JJ, Martinez-Ballarin E, Reiter RJ, Millán-Plano S, Robinson M, Acuña-Castroviejo D. Melatonin improves deferoxamine antioxidant activity in protecting against lipid peroxidation caused by hydrogen peroxide in rat brain homogenates. Neurosci Lett 2002; 232:55-59. PMDI: 11911989.

102. Acuña-Castroviejo D, Escames G, León J, Carazo A, Khaldy H. Mitochondrial regulation by melatonin and its metabolites. Adv Exptl Med Biol 2003; 527:549-557. PMDI: 15206773.

103. Bikjdaouene L, Escames G, León J, Ferrer JMR, Khaldy H, Vives F, Acuña-Castroviejo D. Changes in brain amino acids and nitric oxide after melatonin administration in rats with pentylenetetrazole-induced seizures. J Pineal Res 2003; 35: 54-60. PMDI: 12823614.

104. Coto-Montes A, Tomás-Zapico C, Escames G, León J, Tolivia D, Rodríguez Colunga J, Acuña-Castroviejo D. Specific binding of melatonin in purified cell nuclei from mamarian gland of Swiss mice: Day-night variations and effect of continuous light. J Pineal Res 2003; 34:297-301. PMDI: 12662354.

105. Coto-Montes A, Tomás-Zapico C, Escames G, León J, Tolivia D, Rodríguez Colunga J, Acuña-Castroviejo D. Characterization of melatonin high-affinity binding sites in purified cell nuclei of the hamster (Mesocricetus auratus) harderian gland. J Pineal Res 2003; 34:202-207. PMDI: 12614480.

106. Cutando Soriano A, Gómez Moreno G, Villalba J, Ferrera MJ, Escames G, Acuña-Castroviejo D. Relationships between salivary melatonin levels and periodontal status in diabetic patients. J Pineal Res 2003; 35:239-244. PMDI: 14521628.

107. Escames G, León J, Macías M, Khaldy H, Acuña-Castroviejo D. Melatonin counteracts lipopolysaccharide-induced expression and activity of mitochondrial nitric oxide synthase in rats. FASEB J 2003; 17 (online March, 28):932-934. PMDI: 12670878.

108. Khaldy H, León J, Escames G, Bikjdaouene L, Acuña-Castroviejo D. Synergistic effects of melatonin and deprenyl protect against MPTP-induced mitochondrial damage and DA depletion. Neurobiol Aging 2003; 24:491-500. PMDI: 12600724.

109. Macías M, Escames G, León J, Coto-Montes A, Sbihi Y, Osuna A, Acuña-Castroviejo D. Calreticulin-melatonin. An unexpected relationship. Eur J Biochem 2003; 270:832-840. PMDI: 12603316.

110. Acuña-Castroviejo D. Nuevas bases científicas en la prevención endocrina del envejecimiento: Melatonina y DHEA. Papeles Confidenciales de Medicina, Estética y Longevidad 2004; 7:15-23.

111. Bikjdaouene L, Escames G, Camacho E, León J, Ferrer JMR, Espinosa A, Gallo MA, Luna J, Acuña-Castroviejo D. Effects of some synthetic kynurenines on brain amino acids and nitric oxide after pentylenetetrazole administration to rats. J Pineal Res 2004; 36:267-277. PMDI: 15066052.

112. Camacho E, León J, Entrena A, Velasco G, Dora Carrión M, Escames G, Vivó A, Acuña-Castroviejo D, Gallo MA, Espinosa A. 4,5-dihydro-1H-pyrazole derivatives with inhibitory nNOS activity in rat brain: Synthesis and structure-activity relationship. J Med Chem 2004; 47:5641-5650. PMDI: 15509163.

113. Carrión MD, Camacho E, León J, Escames G, Tapias V, Acuña-Castroviejo D, Gallo MA, Espinosa A. Synthesis and iNOS/nNOS inhibitory activities of new benzoylpyrazoline derivatives. Tetrahedron 2004; 60:4051-4069. PMDI:15509163.

114. Escames G, León J, López LC, Acuña-Castroviejo D. Mechanisms of the NMDA receptor inhibition by melatonin in the rat brain striatum. J Neuroendocrinol 2004; 16:929-935. PMDI: 15584934.

115. Escames G, Khaldy H, León López J, González L, Acuña-Castroviejo D. Changes in iNOS activity, oxidative stress and melatonin levels in hypertensive patients treated with lacidipine. J Hypertens 2004; 22:629-635. PMDI: 15076170.

116. León J, Acuña-Castroviejo D, Sainz RM, Mayo JC, Tan DX, Reiter RJ. Melatonin and mitochondrial function. Life Sci 2004; 75:765-790. PMDI: 15183071.

117. Acuña-Castroviejo D, Escames G, López LC, Hitos AB, León J. Melatonin and nitric oxide: Two required antagonists for mitochondrial homeostasis. Endocrine 2005; 27:159-168. PMDI: 16217129.

118. Acuña-Castroviejo D, Escames G. Stop a la muerte celular en el Parkinson. Guía Universitaria 2005; 507:6-7.

119. Acuña-Castroviejo D, Escames G. Científicos de la UGR estudian el modo de frenar la muerte celular en el parkinson. Andalucía Investiga 2005.

120. Acuña-Castroviejo D, Escames G. Científicos de la Universidad de Granada estudian el modo de frenar la muerte celular en el parkinson. Campus 2005; 238:25-25.

121. Canudas AM, Gutiérrez-Cuesta J, Rodríguez MI, Acuña-Castroviejo D, Sureda F, Camins A, Pallás M. Hyperphosphorylation of microtubule-associated protein tau in senescence-accelerated mouse (SAM). Mech Aging Develop 2005; 126:1300-1304. PMDI: 16171847.

122. Entrena A, Camacho E, Carrión MD, López-Cara LC, Velasco G, León J, Escames G, Acuña-Castroviejo D, Tapias V, Gallo MA, Vivó A, Espinosa A. Kynurenamines as neural nitric oxide synthase inhibitors. J Med Chem 2005; 48:8174-8181. PMDI: 16366599.

123. Furné M, Hidalgo MC, López A, García-Gallego M, Morales AE, Domezain A, Domezain J, Sanz.A. Digestive enzyme activities in adriatic sturgeon Acipenser naccarii and rainbow trout Oncorhynchud mykiss. A comparative study. Aquaculture 2005; 250:391-398.

124. González Puga C, García Navarro A, Escames G, León J, López Cantarero M, Ros E, Acuña-Castroviejo D. Selective CCK-A but not CCK-B receptor antagonists inhibit HT-29 cell proliferation. Synergism with melatonin. J Pineal Res 2005; 39:243-250. PMDI: 16150104.

125. Hassan SM, Maache M, Díaz de la Guardia R, Córdova O, Galiana M, Acuña-Castroviejo D, Martins M, Osuna A. Binding properties and immunolocalization of a fatty acid-binding protein in giardia lamblia. J Parasitol 2005; 91:284-292. PMDI: 15986602.

126. León J, Acuña-Castroviejo D, Escames G, Tan DX, Reiter RJ. Melatonin mitigates mitochondrial malfunction. J Pineal Res 2005; 38:1-9. PMDI: 15617531.

127. Acuña-Castroviejo D, Escames G. Control del extrés oxidativo con el reposo. Medicina Estética 2006; 7:28-33.

128. Acuña-Castroviejo D, Escames G, Reiter RJ. Melatonin therapy in fibromyalgia. J Pineal Res 2006; 40:98-99. PMDI: 16313505.

129. Alvira D, Tajes M, Verdaguer E, Acuña-Castroviejo D, Folch J, Camins A, Pallás M. Inhibition of the cdk5/p25 fragment formation may explain the antiapoptotic effects of melatonin in an experimental model of Parkinson's disease. J Pineal Res 2006; 40:251-258. PMDI: 16499562.

130. Arana C, Cutando A, Ferrera MJ, Gómez Moreno G, Worf CV, Bolaños MJ, Escames G, Acuña-Castroviejo D. Parameters of oxidative stress in saliva from diabetic and parenteral drug addict patients. J Oral Pathol Med 2006; 35:554-559. PMDI: 16968236.

131. Cutando A, Galindo P, Gómez Moreno G, Arana C, Bolaños MJ, Acuña-Castroviejo D, Wang HL. Relationship between salivary melatonin and severity of periodontal disease. J Periodontol 2006; 77:1533-1538. PMDI: 16945031.

132. Escames G, Acuña-Castroviejo D, López LC, Tan DX, Maldonado MD, Sánchez-Hidalgo M, León J, Reiter RJ. Pharmacological utility of melatonin in the treatment of septic shock. J Pharm Pharmacol 2006; 58:1153-1165. PMDI: 16945173.

133. Escames G, López LC, Ortiz F, Ros E, Acuña-Castroviejo D. Age-dependent lipopolysaccharide-induced iNOS expression and multiorgan failure in rats: effects of melatonin treatment. Exptl Gerontol 2006; 41:1165-1173. PMDI: 17049787.

134. Escames G, López LC, Tapias V, Utrilla MP, Reiter RJ, Hitos AB, León J, Rodríguez MI, Acuña-Castroviejo D. Melatonin counteracts inducible mitochondrial nitric oxide synthase-dependent mitochondrial dysfunction in skeletal muscle of septic mice. J Pineal Res 2006; 40:71-78. PMDI: 16313501.

135. León J, Escames G, Rodríguez MI, López LC, Tapias V, Entrena A, Camacho E, Carrión MD, Gallo MA, Espinosa A, Tan DX, Reiter RJ, Acuña-Castroviejo D. Inhibition of neuronal nitric oxide synthase activity by N1-acetyl-5-methoxykynurenamine, a brain metabolite of melatonin. J Neurochem 2006; 98:2023-2033. PMDI: 16945113.

136. López LC, Schuelke M, Quinzii CM, Kanki T, Rodenburg RJT, Naini A, DiMauro S, Hirano M. Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations. Am J Hum Genet 2006; 79:1125-1129. PMDI:17186472.

137. López LC, Escames G, Ortiz F, Ros E, Acuña-Castroviejo D. Melatonin restores the mitochondrial production of ATP in septic mice. Neuroendocrinol Lett 2006; 27:623-630. PMDI: 17159820.

138. López LC, Escames G, Tapias V, Utrilla MP, León J, Acuña-Castroviejo D. Identification of an inducible nitric oxide synthase in diaphragm mitochondria from septic mice. Its relation with mitochondrial dysfunction and prevention by melatonin. Int J Biochem Cell Biol 2006; 38:267-278. PMDI: 16223598.

139. Maldonado MD, Siu AW, Sánchez-Hidalgo M, Acuña-Castroviejo D, Escames G. Melatonin and lipid uptake by murine fibroblasts: clinical implications. Neuro Endocrinol Lett 2006; 27:601-608. PMDI: 17186997.

140. Nogués MR, Giralt M, Romeu M, Mulero M, Sánchez-Martos V, Rodríguez E, Acuña-Castroviejo D, Mallol J. Melatonin reduces oxidative stress in erythrocytes and plasma of senescence-accelerated mice (SAM). J Pineal Res 2006; 41:142-149. PMDI: 16879320.

141. Tomás-Zapico T, Álvarez-García O, Sierra V, Vega-Naredo I, Caballero B, García JJ, Acuña-Castroviejo D, Rodríguez MI, Tolivia D, Rodríguez-Colunga MJ, Coto-Montes A. Oxidative damage in liver of senescence accelerated mice: Gender-related response. Can J Physiol Pharmacol 2006; 84:213-220. PMDI: 16900947.

142. Acuña-Castroviejo D, Escames G, Rodríguez MI, López LC. Melatonin role in the mitochondrial function. Frontiers in Bioscience 2007; 12:947-963. PMDI: 17127351.

143. Acuña-Castroviejo D. A new guest playing with bone and fat. Am J Physiol Reg Integr Comp Physiol 2007; 292:R2206-R2207. PMDI: 17363683.

144. Cutando A, Gómez Moreno G, Arana C, Acuña-Castroviejo D, Reiter RJ. Melatonin: potential functions in the oral cavity. J Periodontol 2007; 78:1094-1102. PMDI: 17539724.

145. Cutando A, Arana C, Gómez Moreno G, Escames G, López A, Ferrera MJ, Reiter RJ, Acuña-Castroviejo D. Local application of melatonin into alveolar sockets of beagle dogs reduces tooth removal-induced oxidative stress. J Periodontol 2007; 78:576-583. PMDI: 17335383.

146. Cutando A, Gómez Moreno G, Arana C, Escames G, Acuña-Castroviejo D. Melatonin reduces oxidative stress because of tooth removal. J Pineal Res 2007; 42:419-420. PMDI: 17439559.

147. Del Blanco Pablos B, Halmi P, Fernández Ibáñez AM, Hernández López de Munain C. Regulación de la recombinación durante el desarrollo en el locus del TCR alfa/delta por enhancers. Inmunología 2007; 26:124-124.

148. Escames G, López LC, Ortiz F, López A, García JA, Ros E, Acuña-Castroviejo D. Attenuation of cardiac mitochondrial dysfunction by melatonin in septic mice. FEBS J 2007; 274:2135-2147. PMDI: 17371545.

149. García Navarro A, González Puga C, Escames G, López LC, López A, López Cantarero M, Camacho E, Espinosa A, Gallo MA, Acuña-Castroviejo D. Cellular mechanisms involved in the melatonin inhibition of HT-29 human colon cancer cell proliferation in culture. J Pineal Res 2007; 43:195-205. PMDI: 17645698.

150. Gómez Moreno G, Cutando Soriano A, Arana C, Galindo P, Bolaños MJ, Acuña-Castroviejo D, Wang HL. Melatonin expression in periodontal disease. J Periodontal Res 2007; 42:536-540. PMDI: 17956466.

151. López-Vicente M, Ortega-Gutiérrez S, Fuentes-Broto L, Martinez-Ballarin E, Miana-Mena.F.J., Acuña-Castroviejo D, García JJ. Melatonin in psychiatry: an update. Arch F M Zarag 2007; 46:58-65.

152. Reiter RJ, Acuña-Castroviejo D, Tan DX. Melatonin therapy in fibromyalgia. Current Pain and Headache Report 2007; 11:339-342. PMDI: 17894923.

153. Rodríguez MI, Carretero M, Escames G, López LC, Maldonado MD, Tan DX, Reiter RJ, Acuña-Castroviejo D. Chronic melatonin treatment prevents age-dependent cardiac mitochondrial dysfunction in senescence-accelerated mice. Free Rad Res 2007; 41:15-24. PMDI: 17164175.

154. Rodríguez MI, Escames G, López LC, García JA, Ortiz F, López A, Acuña-Castroviejo D. Melatonin administration prevents cardiac and diaphragmatic mitochondrial oxidative damage in senescence accelerated mice. J Endocrinol 2007; 194:637-643. PMDI: 17761903.

155. Rodríguez MI, Escames G, López LC, López A, García JA, Ortiz F, Acuña-Castroviejo D. Chronic melatonin treatment reduces the age-dependent inflammatory process in senescence-accelerated mice. J Pineal Res 2007; 42:272-279. PMDI: 17349026.

156. Molina-Carballo A, Muñoz-Hoyos A, Sánchez-Forte M, Uberos-Fernández J, Moreno-Madrid F, Acuña-Castroviejo D. Melatonin increases following convulsive seizures may be related to its anticonvulsant properties at physiological concentrations. Neuropediatrics 2007; 38:122-125. PMDI: 17985260.

157. Valentino ML, Mertí R, Tadesse S, López LC, Manes JL, Lyzak J, Hahn A, Carelli V, Hirano M. Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). FEBS Lett 2007; 581:3410-3414. PMDI:17612528.

158. Agil A, Fraile R, Acuña-Castroviejo D. Changes in plasma susceptibility to lipid peroxidation and vitamin C in preterm and full-term neonates. Arch Med Sci 2008; 4:324-328.

159. Akman HO, Dorado B, López LC, García-Cazorla A, Vil-a MR, Tanabe LM, Dauer WT, Bonilla E, Tanji K, Hirano M. Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance. Hum Mol Genet 2008; 17:2433-2440. PMDI:18467430.

160. Camacho E, Carrión MD, López-Cara LC, Gómez-Pérez V, Entrena A, Gallo MA, Espinosa A, Escames G, Acuña-Castroviejo D. Synthesis and biological evaluation of phenyl-pyrrole derivatives as nitric oxide synthase inhibitors. Drugs Future 2008; 33:204-205.

161. Carrión MD, Pineda de las Infantas MJ, Camacho E, Gallo MA, Espinosa A, Entrena A, Escames G, García JA, Acuña-Castroviejo D. Synthesis and biological evaluation of new 2-phenyl-2,3-dihydro-1,3,4-thiadaizole derivatives as nitric oxide synthase inhibitors. Drugs Future 2008; 33:204-205.

162. Carrión MD, López-Cara LC, Camacho E, Tapias V, Escames G, Acuña-Castroviejo D, Espinosa A, Gallo MA, Entrena A. Pyrazoles and pyrazolines as neural and inducible nitric oxide synthase (nNOS and iNOS) potential inhibitors (III). Eur J Med Chem 2008; 43:2579-2591. PMDI: 18325637.

163. Escames G, Acuña-Castroviejo D, López LC, Dayoub JC. Melatonin and septic shock. Approaches to Aging Control 2008; 11:10-16.

164. Lagier Tourenine C, Tazir M, López LC, Quinzii CM, Assoum M, Drouput N, Busso C, Makri S, Ali-Pacha L, Benhassine T, Anheim M, Lynch DR, Thibault C, Plewniak F, Bianchetti L, Tranchant C, Poch O, DiMauro S, Mandel JL, Barros MH, Hirano M, Koening M. ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency. Am J Hum Genet 2008; 82:661-672. PMDI:18319074.

165. Quinzii CM, López LC, Naini A, DiMauro S, Hirano M. Human CoQ10 deficiences. Biofactors 2008; 32:113-118. PMDI:19096106.

166. Quinzii CM, López LC, Von-Moltke J, Naini A, Krishna S, Schuelke M, Salviati L, Navas P, DiMauro S, Hirano M. Respiratory chain dysfunction and oxidative stress correlate with severity of primary CoQ 10 deficiency. FASEB J 2008; 22:1874-1885. PMDI:18230681.

167. Rodríguez MI, Escames G, López LC, García JA, Ortiz F, Sánchez V, Romeu M, Acuña-Castroviejo D. Improved mitochondrial function and increased life span after chronic melatonin treatment in senescent prone mice. Exptl Gerontol 2008; 43:749-756. PMDI: 18485648.

168. Acuña-Castroviejo D, Escames G, López LC, Ortiz F, López A, García JA. Evidencias de la utilidad de la melatonina frente al envejecimiento y los procesos neurodegenerativos. Psicogeriatría 2009; 1:1-19.

169. Acuña-Castroviejo D. Utilidad de la melatonina en la enfermedad de Parkinson. Parkinson Málaga 2009; 3:6-7.

170. Acuña-Castroviejo D, Escames G. Melatonina, ritmo sueño/vigilia y fibromialgia. Biorritmes 2009; 18:11-13.

171. Carretero M, Escames G, López LC, Venegas C, Dayoub JC, García L, Acuña-Castroviejo D. Long-term melatonin administration protects brain mitochondria from aging. J Pineal Res 2009; 47:192-200. PMDI: 19573039.

172. Claramunt RM, López C, Pérez-Medina C, Pérez-Torralba M, Elguero J, Escames G, Acuña-Castroviejo D. Fluorinated Indazoles as Novel Selective Inhibitors of Nitric Oxide Synthase (NOS): Synthesis and Biological Evaluation. Bioorgan Med Chem 2009; 17:6180-6187. PMDI: 19679481.

173. Duncan AJ, Bitner-Glindzicz M, Meunier B, Costello H, Hargreaves IP, López LC, Hirano M, Quinzii CM, Sadowski MI, Hardy J, Singleton A, Clayton PT, Rahman S. A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease. Am J Hum Genet 2009; 84:558-566. PMDI:19375058.

174. Escames G, Acuña-Castroviejo D. Melatonina, análogos sintéticos y el ritmo sueño/vigilia. Rev Neurol 2009; 48:245-254. PMDI: 19263393.

175. Liang WC, Ohkuma A, Hayashi YK, López LC, Hirano M, Nonaka I, Noguchi S, Chen LH, Jong YJ, Nishino I. ETFDH mutations, CoQ10 levels, and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Neuromuscul Disord 2009; 19:212-216. PMDI:19249206.

176. López-Cara LC, Camacho E, Carrión MD, Tapias V, Gallo MA, Escames G, Acuña-Castroviejo D, Espinosa A, Entrena A. Phenylpyrrole derivatives as neural and inducible nitric oxide synthase (nNOS and iNOS) inhibitors. Eur J Med Chem 2009; 44:2655-2666. PMDI: 19117642.

177. López A, García JA, Escames G, Venegas C, Ortiz F, López LC, Acuña-Castroviejo D. Melatonin protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential, and superoxide anion production. J Pineal Res 2009; 46:188-198. PMDI:19054298.

178. López LC, Akman HO, García-Cazorla A, Dorado B, Martí R, Nishino I, Tadesse S, Pizzorno G, Shungu D, Bonilla E, Tanji K, Hirano M. Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase deficient mice. Hum Mol Genet 2009; 18:714-722. PMDI:19028666.

179. Okuma A, Noguchi S, Sugie H, Malicdan MC, Fukuda T, Shimazu K, López LC, Hirano M, Hayashi YK, Nonaka I, Nishino I. Clinical and genetic analysis of lipid storage myopathies. Muscle Nerve 2009; 39:333-342. PMDI:19208393.

180. Tapias V, Escames G, López LC, Entrena A, Camacho E, Espinosa A, Gallo MA, Acuña-Castroviejo D. Melatonin and its brain metabolite N1-acetyl-5-methoxykynuramine prevent mitochondrial nitric oxide synthase induction in parkinsonian mice. J Neurosci Res 2009; 87:3002-3010. PMDI: 19437546.

181. Acuña-Castroviejo D. Melatonin in brain: From circadian signal to neuroprotection. The Open Neuroendocrinology J 2010; 3:68-71.

182. Chahbouni M, Escames G, Venegas C, Sevilla B, García JA, López LC, Muñoz-Hoyos A, Molina-Carballo A, Acuña-Castroviejo D. Melatonin treatment normalizes plasma pro-inflammatory cytokines and nitrosative/oxidative stress in patients suffering from Duchenne muscular dystrophy. J Pineal Res 2010; 48:282-289. PMDI: 20210854.

183. Cuesta S, Kireev R, Forman K, García C, Escames G, Ariznavarreta C, Vara E, Tresguerres JA. Melatonin improves inflammation processes in liver of senescence-accelerated prone male mice (SAMP8). Exptl Gerontol 2010; 45:950-956. PMDI:20817086.

184. Escames G, López A, García JA, García L, Acuña-Castroviejo D, García JJ, López LC. The role of mitochondria in the aging brain and the effects of melatonin. Current Neuropharmacology 2010; 8:182-193. PMDI: 21358969.

185. Forman K, Vara E, García C, Kireev R, Cuesta S, Acuña-Castroviejo D, Tresguerres JA. Beneficial effects of melatonin on cardiological alterations in a murine model of accelerated aging. J Pineal Res 2010; 49:312-320. PMDI: 20738757.

186. Forman K, Vara E, García C, Ariznavarreta C, Escames G, Tresguerres JA. Cardiological aging in SAM model: effect of chronic treatment with growth hormone. Biogerontology 2010; 11:275-286. PMDI:19731067.

187. López LC, Acuña-Castroviejo D, del Pino A, Tejada MA, Escames G. Mitochondrial disorders therapy: The utility of melatonin. The Open Biology Journal 2010; 3:53-65.

188. López LC, Quinzii CM, Area E, Naini A, Rahman S, Schuelke M, Salviati L, DiMauro S, Hirano M. Treatment of CoQ10 Deficient Fibroblasts with Ubiquinone, CoQ Analogs, and Vitamin C: Time- and Compound-Dependent Effects. Plos One 2010; 5:E11897-E11897. PMDI:20689595.

189. López LC, Escames G, López A, García JA, Doerrier C, Acuña-Castroviejo D. Melatonin, neurogenesis, and aging brain. The Open Neuroendocrinology J 2010; 3:121-133.

190. Pozo MJ, Gomez-Pinilla PJ, Camello-Almaraz C, Martin-Cano E, Pascua P, Rol MA, Acuña-Castroviejo D. Melatonin, a potential therapeutic agent for smooth muscle-related pathological conditions and aging. Curr Med Chem 2010; 17:4150-4165. PMDI: 20939818.

191. Quinzii CM, López LC, Gilkerson RW, Dorado B, Coku J, Naini A, Lagier-Tourenne C, Schuelke M, Salviati L, Carrozzo R, Santorelli F, Rahman S, Tazir M, Koening M, DiMauro S, Hirano M. Reactive oxygen species, oxidative stress, and cell death correlate with level of CoQ10 deficiency. FASEB J 2010; 74:A439-A439. PMDI:20495179.

192. Rusanova I, Escames G, Cossio G, de Borace R, Chahbouni M, López LC, Díez T, Acuña-Castroviejo D. Oxidative stress status, clinical outcome, and -globin haplotypes in sickle cell anemic pediatric patients. Eur J Haematol 2010; 85:529-537. PMDI: 20846340.

193. Serrano E, Venegas C, Escames G, Sánchez-Muñoz C, Zabala M, Puertas A, de Haro T, Gutiérrez A, Castillo MJ, Acuña-Castroviejo D. Antioxidant defense and inflammatory response in professional road cyclists performing a 4-day competition. J Sports Sci 2010; 28:1047-1056. PMDI: 20686993.

194. Acuña-Castroviejo D, Tapias V, López LC, Doerrier C, Camacho E, Carrión MD, Mora F, Espinosa A, Escames G. Protective effect of synthetic kynurenines on 1-methyl-4-phenyl-1,2,3,5-tetrahydropyridine-induced parkinsonism in mice. Brain Res Bull 2011; d85:133-140. PMDI: 21419832.

195. Acuña-Castroviejo D, López LC, Escames G, López A, García JA, Reiter RJ. Melatonin-mitochondria interplay in health and disease. Curr Top Med Chem 2011; 11:221-240. PMDI: 21244359.

196. Chahbouni M, Escames G, López LC, Sevilla B, Doerrier C, Muñoz-Hoyos A, Molina-Carballo A, Acuña-Castroviejo D. Melatonin treatment counteracts the hyperoxidative status in erythrocytes of patients suffering from Duchenne muscular dystrophy. Clin Biochem 2011; 44:853-858. PMDI: 21515247.

197. Claramunt RM, López C, López A, Pérez-Medina C, Pérez-Torralba M, Alkorta I, Elguero J, Escames G, Acuña-Castroviejo D. Synthesis and biological evaluation of indazole derivatives. Eur J Med Chem 2011; 46:1439-1447. PMDI: 21334118.

198. Cuesta S, Kireev R, Forman K, García C, Acuña-Castroviejo D, Vara E, Tresguerres JA. Growth hormone can improve insulin resistance and differentiation in pancreas of senescence accelerated male mice (SAMP8). Growth Horm & IGF Research 2011; 21:63-68. PMDI:21239198.

199. Cuesta S, Kireev R, García C, Forman K, Escames Rosa G, Vara E, Tresguerres JAF. Beneficial effect of melatonin treatment on inflammation, apoptosis and oxidative stress on pancreas of a senescence accelerated mice model. Mech Aging Develop 2011; 132:573-582. PMDI:22024129.

200. Dayoub JC, Ortiz F, López LC, Venegas C, del Pino Zumaquero A, Roda O, Sánchez-Montesinos I, Acuña-Castroviejo D, Escames G. Synergism between melatonin and atorvastatin against endothelial cell damage induced by lipopolysaccharide. J Pineal Res 20111; 51:324-330. PMDI: 21585521.

201. Del Arco A, Segovia G, de Blas M, Garrido P, Acuña-Castroviejo D, Pamplona R, Mora F. Prefrontal cortex, caloric restriction and stress during aging: studies on domapine and acetylcholine release, BDNF and working memory. Behav Brain Res 2011; 216:136-145. PMDI: 20655333.

202. Forman K, Vara E, García C, Kireev R, Cuesta S, Escames G, Tresguerres JA. Effect of a combined treatment with growth hormone and melatonin in the cardiological aging on male SAMP8 mice. J Gerontol A Biol Sci Med Sci 2011; 66:823-834. PMDI:21665987.

203. Garcia-Garcia FJ, Gutierrez-Avila G, Alfaro-Acha A, Amor Andres MS, de los Angeles de la Torre Lanza M, Escribano Aparicio MV, Humanes Aparicio S, Larrion Zugasti JL, Gomez-Serranillo Reus M, Rodriguez-Artalejo F, Rodriguez-Mañas L, Alonso Bouzón C, Castro Rodriguez M, Areosa A, El Assar de la Fuente M, Sanchez Ferrer A, Angulo J, Izquierdo Redin M, Larrion Zugasti JL, Viña J, Gambini J, Borrás C, Tresguerres JA, de la Fuente del Rey M, Acuña-Castroviejo D, Antonio Madrid J, Guerrero Montavez JM, Moreno Casbas T. The prevalence of frailty syndrome in an older population from Spain. The Toledo Study for Healthy Aging. J Nutr Health Aging 2011; 15:852-856. PMDI: 22159772.

204. García JJ, Piñol-Ripoll G, Martinez-Ballarin E, Fuentes-Broto L, Miana-Mena.F.J., Venegas C, Caballero B, Escames G, Coto-Montes A, Acuña-Castroviejo D. Melatonin reduces membrane rigidity and oxidative damage in the brain of SAM mice. Neurobiol Aging 2011; 32:2045-2054. PMDI:20096480.

205. López-Ramos JC, Jurado-Parras MT, Sanfeliu C, Acuña-Castroviejo D, Delgado-García JM. Learning capabilities and CA1-prefrontal synaptic plasticity in a mice model of accelerated senescence. Neurobiol Aging 2011; 33:627-e13-26. PMDI: 21664007..

206. Rusanova I, Cossio G, Moreno B, Perea FJ, de Borace R, Perea M, Escames Rosa G, Acuña-Castroviejo D. -globin gene cluster haplotypes in sickle cell patients from Panama. Am J Hum Biol 2011; 23:377-380. PMDI: 21387457.

207. Venegas C, Cabrera C, García Corzo L, Escames G, Acuña-Castroviejo D, López LC. Determination of coenzyme Q10, coenzyme Q9 and melatonin content
in virgin argan oils: comparison with other vegetable edible oils. J Agric Food Chem 2011; 59:12102-12108. PMDI: 22007968.

208. Acuña-Castroviejo D, Carretero M, Doerrier C, López LC, García Corzo L, Tresguerres JA, Escames Rosa G. Melatonin protects lung mitochondria from aging. Age 2012; 34:681-692. PMDI: 21614449.

209. Camacho ME, Carrión MD, López-Cara LC, Entrena A, Gallo MA, Espinosa A, Escames G, Acuña-Castroviejo D. Melatonin synthetic analogues as nitric oxide synthase inhibitors. Mini Rev Med Chem 2012; 12:600-617. PMDI: 22512552.

210. Escames G, López LC, García JA, García Corzo L, Ortiz F, Acuña-Castroviejo D. Mitochondrial DNA and inflammatory diseases. Hum Genetics 2012; 131: 167-173. PMDI: 21735170.

211. Escames G, Öztürk G, Baño-Otálora B, Pozo MJ, Madrid JA, Serrano E, Concepción M, Acuña-Castroviejo D. Exercise and melatonin: Reciprocal benefits. J Pineal Res 2012; 52:1-11. PMDI: 21848991.

212. García-Mesa Y, Giménez-Llort L, López LC, Venegas C, Cristófol R, Escames G, Acuña-Castroviejo D, Sanfeliu C. Melatonin plus physical exercise are highly neuroprotective in the 3xTg-AD mouse. Neurobiol Aging 2012; 33:1124.e13-29- PMDI: 22177720.

213. Lopez-Cara LC, Dora Carrión M, Entrena A, Gallo MA, Espinosa A, López A, Escames Rosa G, Acuña-Castroviejo D, Camacho E. 1,3,4-Thiadiazole derivatives as selective inhibitors of iNOS versus nNOS: Synthesis and structure-activity dependence. Eur J Med Chem 2012; 50:129-139. PMDI: 22336385.

214. Öztürk G, Akbulut KG, Güney S, Acuña-Castroviejo D. Age-related changes in the rat brain mitochondrial antioxidative enzyme ratios: Modulaton by melatonin. Exptl Gerontol 2012; 47:706-711. PMDI: 22796061.

215. Rosales-Corral SA, Acuña-Castroviejo D, Tan DX, López-Armas G, Cruz-Ramos J, Munoz R, Melnikov VG, Manchester LC, Reiter RJ. Accumulation of exogenous amyloid-beta peptide in hippocampal mitochondria causes their dysfunction: a protective role for melatonin. Oxid Med Cell Longev 2012; 2012:843649- PMDI: 22666521.

216. Rosales-Corral SA, Acuña-Castroviejo D, Coto-Montes A, Boga JA, Manchester LC, Fuentes-Broto L, Korkmaz A, Ma S, Tan DX, Reiter RJ. Alzheimer's disease: pathological mechanisms and the beneficial role of melatonin. J Pineal Res 2012; 52:167-202. PMDI: 22107053.

217. Srinivasan V, Zakaria R, Othman Z, Lauterbach EC, Acuña-Castroviejo D. Agomelatine in depressive disorders. its novel mechanism of action. J Neuropsychiatr Clin Neurosci 2012; 24:290-308. PMDI: 23037643.

218. Srinivasan V, Lauterbach EC, Ho KY, Acuña-Castroviejo D, Zakaria R, Brzezinski A. Melatonin and antinociception: Its therapeutic applications. Curr Neuropharmacol 2012; 10:167-178. PMDI: 23204986.

219. Tan DX, Manchester LC, Liu X, Rosales-Corral SA, Acuña-Castroviejo D, Reiter RJ. Mitochondria and chloroplasts as the original sites of melatonin synthesis: a hypothesis related to melatonin's primary function and evolution in eukaryotes. J Pineal Res 2012; Doi:10.1111/jpi.12026:PMDI: 23137057.

220. Venegas C, García JA, Doerrier C, Volt H, Escames G, López LC, Reiter RJ, Acuña-Castroviejo D. Analysis of the daily changes of melatonin receptors in the rat liver. J Pineal Res 2012; Doi:10.1111/jpi.12019. PMDI: 23110416.

221. Venegas C, García JA, Escames G, Ortiz F, López A, Doerrier C, García Corzo L, López LC, Acuña-Castroviejo D. Extrapineal melatonin: Analysis of its subcellular distribution and daily fluctuations. J Pineal Res 2012; 52:217-227. PMDI: 21884551.

222. García-Corzo L, Luna-Sánchez M, Doerrier C, García JA, Guarás A, Acín-Pérez R, Bullejos_Peregrín J, López A, Escames G, Enríquez JA, Acuña-Castroviejo D, López LC. Dysfunctional Coq9 protein causes predominant encephalomyopathy associated with CoQ deficiency. Hum Mol Genet 2013; doi: 10.1093/hmg/dds530:PMDI: 23255162.

223. Reiter RJ, Rosales-Corral SA, Liu XY, Acuña-Castroviejo D, Escames G, Tan DX. Melatonin in the oral cavity: physiological and pathological implications. J Periodontal Res 2014; doi: 10.1111/jre.12176. PMID: 24665831.

224. García-Corzo L, Luna-Sánchez M, Doerrier C, Ortiz F, Escames G, Acuña-Castroviejo D, López C. Ubiquinol-10 ameliorates mitochondrial encephalopathy associated with CoQ deficiency. Biochim Biophys Acta 2014; 1842:893-901. PMDI: 24576561.

225. Acuña-Castroviejo D, Escames G, Venegas C, Díaz-Casado ME, Lima-Cabello E, López LC, Rosales-Corral S, Tan DX, Reiter RJ. Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci 2014; doi:10.1007/s00018-014-1579-2. PMID: 24554058.

226. Martin-Cano FE, Camello-Almaraz C, Acuña-Castroviejo D, Pozo MJ, Camello PJ. Age-related changes in mitochondrial function of mouse colonic smooth muscle: beneficial effects of melatonin. J Pineal Res 2014; doi:10.1111/jpi.12109. PMDI: 24313280.

227. Ortiz F, García JA, Acuña-Castroviejo D, Doerrier C, López A, Venegas C, Volt H, Luna-Sánchez M, López LC, Escames G. The beneficial effects of melatonin against heart mitochondrial impairment during sepsis: inhibition of iNOS and preservation of nNOS. J Pineal Res 2014; 56:71-81. PMDI: 24117944.

228. Leonardo-Mendonca, R. C., M. Concepcion-Huertas, E. Guerra-Hernandez, M. Zabala, G. Escames, D. Acuna-Castroviejo. Redox status and antioxidant response in professional cyclists during training. Eur j Sport Sci 2014; 830-838. PMID: 24803271.

229. Navarro-Alarcon, M., F. J. Ruiz-Ojeda, R. M. Blanca-Herrera, A. Serrano MM, D. Acuna-Castroviejo, G. Fernandez-Vazquez, A. Agil. Melatonin and metabolic regulation: a review. Food Funct 2014; 2806-2832. PMID: 25207999.

230. Paredes, S. D., K. A. Forman, C. Garcia, E. Vara, G. Escames, J. A. Tresguerres. Protective actions of melatonin and growth hormone on the aged cardiovascular system. Horm Mol Biol Clin Investig 2014; 79-88. PMID: 25390004.

231. Lima-Cabello, E., M. E. Diaz-Casado, J. A. Guerrero, B. B. Otalora, G. Escames, L. C. Lopez, R. J. Reiter, D. Acuna-Castroviejo. A review of the melatonin functions in zebrafish physiology. J Pineal Res 2014; 1-9. PMID: 24920150.

232. Moreau, K., A. Fleming, S. Imarisio, A. López Ramírez, J. L. Mercer, M. Jiménez-Sánchez, C. F. Bento, C. Puri, E. Zavodsky, F. Siddiqi, C. P. Lavau, M. Betton, C. J. O'Kane, D. S. Wechsler, D. Rubinsztein. PICALM modulates autophagy activity and tau accumulation. Nat Commun 2014; 34-44. PMID: 25241929.

233. Abdel Moneim, A. E., F. Ortiz, R. C. Leonardo-Mendonca, R. Vergano-Villodres, J. A. Guerrero-Martinez, L. C. Lopez, D. Acuna-Castroviejo, G. Escames. Protective effects of melatonin against oxidative damage induced by Egyptian cobra (Naja haje) crude venom in rats. Acta Trop 2015; 58-65. PMID: 25542296.

234. Leonardo-Mendonça, R., A. Martínez-Nicolás, C. de Teresa Galván, J. Ocaña-Wilhelmi, I. Rusanova, E. Guerra-Hernandez, G. Escames, D. Acuña-Castroviejo. The benefits of four weeks of melatonin treatment on circadian patterns in resistance-trained athletes. Chronobiol Int 2015; PMID: 26361788.

235. Luna-Sanchez, M., E. Diaz-Casado, E. Barca, M. A. Tejada, A. Montilla-Garcia, E. J. Cobos, G. Escames, D. Acuna-Castroviejo, C. M. Quinzii, L. C. Lopez. The clinical heterogeneity of coenzyme Q10 deficiency results from genotypic differences in the Coq9 gene. EMBO Mol Med 2015; 670-687. PMID: 25802402.

236. Garcia, J. A., H. Volt, C. Venegas, C. Doerrier, G. Escames, L. C. López, D. Acuña-Castroviejo. Disruption of the NF-kappaB/NLRP3 connection by melatonin requires retinoid-related orphan receptor-alpha and blocks the septic response in mice. FASEB J 2015; 3863-3875. PMID: 26045547.

237. Acuna-Castroviejo, D., P. Bueno-Larano. Comment on "Serum melatonin levels are associated with mortality in severe septic patients" by Lorente et al., J Crit Care (2015), http://dx.doi.org/10.1016/j.jcrc.2015.03.023. J Crit Care 2015; 1133. PMID: 26025099.

238. Reiter, R. J., S. A. Rosales-Corral, X. Y. Liu, D. Acuna-Castroviejo, G. Escames, D. X. Tan. Melatonin in the oral cavity: physiological and pathological implications. J Periodontal Res 2015; 9-17. PMID: 24665831.

239. Ortiz, F., D. Acuna-Castroviejo, C. Doerrier, J. C. Dayoub, L. C. Lopez, C. Venegas, J. A. Garcia, A. Lopez, H. Volt, M. Luna-Sanchez, G. Escames. Melatonin blunts the mitochondrial/NLRP3 connection and protects against radiation-induced oral mucositis. J Pineal Res 2015; 34-49. PMID: 25388914.

240. Doerrier, C., J. A. Garcia, H. Volt, M. E. Diaz-Casado, E. Lima-Cabello, F. Ortiz, M. Luna-Sanchez, G. Escames, L. C. Lopez, D. Acuna-Castroviejo. Identification of mitochondrial deficits and melatonin targets in liver of septic mice by high-resolution respirometry. Life Sci 2015; 158-165. PMID: 25498899.

241. Doerrier, C., J.A. García, H. Volt, E. Díaz-Casado, M. Luna-Sánchez, B. Fernández-Gil, G. Escames, L.C. López, D. Acuña-Castroviejo. Permeabilized myocardial fibers as model to detect mitochondrial dysfunction during sepsis and melatonin effects without disruption of mitochondrial network. Mitochondrion 2015; 56-63. PMID: 26748191.

242. Nieto, C. I., M. P. Cabildo, M. P. Cornago, D. Sanz, R. M. Claramunt, M. C. Torralba, M. R. Torres, J. Elguero, J. A. García, A. López, D. Acuña-Castroviejo. Fluorination effects on NOS inhibitory activity of pyrazoles related to curcumin. Molecules 2015; 15643-15665. PMID: 26343623.

243. Ortiz, F., B. Fernández-Gil, A. Guerra-Librero, L. C. López, D. Acuña Castroviejo, G. Escames. Devices made with nonmetallic and metallic nanoparticles neutralize electromagnetic radiations reduces oxidative stress and inflammatory status in normal subjects. Eur J Int Med 2016.

244. Forman, K., E. Vara, C. García, R. Kireev, S. Cuesta, D. Acuña-Castroviejo, J. A. Tresguerres. Influence of aging and growth hormone on different members of the NFkB family and IkB expression on heart from a murine model of senescence-accelerated aging. Exp Gerontol 2016; 114-120. PMID: 26581911.

255. Puig, A., L. Rancan, S. D. Paredes, A. Carrasco, G. Escames, E. Vara, J. A. Tresguerres. Melatonin decreases the expression of inflammation and apoptosis markers in the lung of a senescence-accelerated mice model. Exp Gerontol 2016; 1-7. PMID: 26656745.

246. Sayed, R.K.A., E. Chacin de Leonardis, J. Guerrero-Martínez, I. Rahim, D. M. Mokhtar, A. M. Saleh, K. E. H. Abdalla, M. J. Pozo, G. Escames, L. C. López, D. Acuña-Castroviejo. Identification of morphological markers of sarcopenia at early stage of aging in skeletal muscle of mice. Exp Gerontol 2016; PMID: 27435496.

247. Cardinali, D. P., G. Escames, D. Acuña Castroviejo, F. Ortiz, B. Fernández-Gil, A. Guerra-Librero, S. García-López, Y. C. Shen, J. Florido. Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance. J Integr Oncol 2016.

248. Díaz Casado, E., E. Lima-Cabello, J.A. García, C. Doerrier, P. Aranda, R.K.A. Sayed, A. Guerra-Librero, G. Escames, L.C. López, D. Acuña Castroviejo. Melatonin rescues zebrafish embryos from the parkinsonian phenotype restoring the Parkin/PINK1/DJ-1/MUL1 network J Pineal Res 2016; PMID: 27064726.

249. Volt, H., J. A. García, C. Doerrier, M. E. Díaz-Casado, A. Guerra-librero, L. C. López, G. Escames, J. A. Tresguerres, D. Acuña-Castroviejo. Same molecule but different expression: aging and sepsis trigger NLRP3 inflammasome activation, a target of melatonin. J Pineal Res 2016; 193-205. PMID: 26681113.

250. Pineda de las Infantas, M. J., M. D. Carrión, M. Chayah, L. C. López-Cara, M. A. Gallo, D. Acuña-Castroviejo, M. E. Camacho. Synthesis of oxadiazoline and quinazolinone derivatives and their biological evaluation as nitric oxide synthase inhibitors. Med Chem Res 2016; 1260-1273.

251. López-Armas, G., M. E. Flores Soto, V. Chaparro-Huerta, L. F. Jave-Suárez, S. Soto-Rodríguez, I. Rusanova, D. Acuña-Castroviejo, O. González-Pérez, R. E. González-castañeda. Prophylactic role of oral melatonin administration on neurogenesis in adult Balb/C mice during REM sleep deprivation. Oxid Med Cell Long 2016; Article ID 2136902. PMID: 27579149.

Nuestros servicios

El insomnio y, en general, el trastorno del ritmo sueño/vigilia, refleja una alteración más profunda del reloj biológico, que está relacionado con muchas otras patologías como fibromialgia y fatiga crónica, astenia, trastornos metabólicos, hormonales y desequilibrios de la nutrición, enfermedades neurodegenerativas e inflamatorias, cáncer, así como el envejecimiento y patológico.

Mediante una serie de pruebas que se indican abajo, en el IiMEL evaluamos la función del reloj biológico, los trastornos de los ritmos circadianos y de la producción de melatonina, así como las causas de las alteraciones del sueño, identificamos su relación con otras patologías antes citadas, y proponemos el tratamiento adecuado.

  • Calidad del sueño

    Ya que el ritmo sueño/vigilia refleja directamente cómo está funcionando el reloj biológico, una correcta evaluación de la calidad de sueño requiere el análisis de la estructura (cronotipo) y funcionamiento del reloj biológico endógeno, y su relación con la alteración de los ritmos biológicos, o cronodisrupción.

    Nos permite identificar las causas y el tipo de cronodisrupción, para proceder a su reparación y restaurar el ritmo del sueño.


  • Niveles de melatonina

    El análisis de la melatonina se puede realizar en orina (midiendo 6-sulfatoximelatonina), suero o saliva. La saliva es la mejor opción y menos invasiva, ya que refleja con total seguridad sus niveles en sangre. La determinación de los niveles de melatonina en saliva a lo largo de las 24 horas refleja el fenotipo circadiano.

    De esta forma, conocemos si existen trastornos en la amplitud, duración, y adelanto o retraso de fase en el fenotipo circadiano de los ritmos con respecto al ritmo ideal representado por el cronotipo genético, para proceder a normalizarlo.


  • Proceso de envejecimiento

    Ya que el envejecimiento se inicia con un proceso de cronodisrupción, continúa con una fase de activación inmunitaria, sigue con aumento de estrés oxidativo, y termina con disfunción mitocondrial, valoramos aquí el daño oxidativo y defensa antioxidante, el daño nitrosativo y la activación inflamatoria, y la función mitocondrial.

    Podemos conocer de esta forma la magnitud del proceso de envejecimiento, para proponer medidas correctoras y preventivas.


  • Estrés oxidativo y potencial antioxidante

    Determinamos los marcadores de daño oxidativo a lípidos y proteínas, así como la actividad de los sistemas endógenos de defensa antioxidante, así como la capacidad de generación de agentes reductores a nivel intracelular y extracelular, cuyo funcionamiento, en tándem, nos da una visión global del potencial antioxidante del organismo.

    Con estos datos, identificamos en qué lugar o lugares del tándem antioxidante/reductor se encuentra el fallo que lleva al acúmulo de radicales libres. Entonces, podemos corregir y compensar esos defectos de manera adecuada para lograr el estado de equilibrio oxidativo.


  • Potencial antiinflamatorio

    Para valorar el potencial y capacidad de respuesta y activación inflamatorias, medimos aquí diversos parámetros de la respuesta de la inmunidad innata, desde la generación de óxido nítrico y el daño nitrosativo, hasta los niveles de citoquinas pro- y antiinflamatorias.

    Estos datos nos dan una visión global de cuál es el grado de activación del sistema inmunitario, proporcionándonos la información necesaria para su corrección.


  • Función mitocondrial

    La función mitocondrial está directamente ligada a la formación de radicales libres, por lo que se pude dañar fácilmente. Aquí determinamos diversos marcadores en suero y en células mononucleares periféricas, incluyendo melatonina y CoQ10, que nos indican la salud de la función mitocondrial.

    Estos estudios nos permiten restaurar la mitocondria, que es es la central bioenergética de la célula, cuyo funcionamiento es crítico para que el organismo responda de manera saludable en cada momento.


  • Otros marcadores del estado de salud

    Los niveles de hormonas, que disminuyen con la edad y ante determiandos tratamietnos farmacológicos; el contenido en microelementos, necesarios para el buen funcionamiento del organismo; los niveles de vitaminas, así como el acúmulo de toxinas, están directamente relacionados con el envejecimiento y enfermedades asociadas al mismo.

    La determinación de esos parámetros o de alguno de ellos nos es importante identificar muchos estados carenciales y/o tóxicos, que permitirá un adecuado diagnóstico del estado de salud y tomar las medidas correctoras adecuadas.


  • Informe personalizado y tratamiento

    Con las determinaciones realizadas aquí, tenemos un criterio importante para diagnosticar el problema de salud, realizar un informe personalizado en cada caso, y plantear una pauta de tratamiento específico, que devuelva la normalidad a aquellas situaciones que se identifiquen como alteradas.

    El fin último del IiMEL es identificar y corregir los problemas de salud mediante los análisis más específicos y menos invasivos, y las terapias más concretas para realizar un tratamiento definido y personalizado.