Cristiane Lopes

Calcium-dependent modulation by melatonin of the circadian rhythm in malarial parasites.

he development of malarial parasites is a complex process involving both intracellular and extracellular phases. Intraerythrocytic maturation proceeds through well-defined stages, termed rings, trophozoites and schizonts. In vivo, transition to a new stage and invasion of new erythrocytes are highly synchronous. The timing of these processes varies between Plasmodium species, but is always a multiple of 24 h. The simultaneous appearance of billions of individual parasites in the bloodstream may represent an efficient evolutionary strategy to escape the defence mechanisms of the host. The synchronicity of these processes is rapidly lost in culture, indicating the possible involvement of a host-derived signal, although the nature of this signal is presently unknown. Here we show that the hormone melatonin modifies the development of malarial parasites in vitro, that in vivo surgical ablation of the pineal gland leads to reduced synchronicity in the maturation process of Plasmodium, an effect that is reversed upon treatment with melatonin, and that in vivo inhibition of melatonin receptors mimics the effect of pinealectomy. We also demonstrate that melatonin, through activation of specific receptors coupled to phospholipase C activation, causes release of Ca from the intracellular stores of Plasmodium grown in vitro. We therefore propose that circadian changes in melatonin concentration in the host represent a key signal that controls synchronous maturation of Plasmodium in vivo. In search of a host-derived signal that undergoes circadian changes in mammals (and other vertebrates), we considered melatonin as a potential candidate. Melatonin is synthesized and released by the pineal gland during darkness, and this hormone is thought to participate in regulation of circadian rhythms in many eukaryotes, including vertebrates, invertebrates, higher plants and dinoflagellates. Not only does melatonin release exhibit a circadian rhythm, but the molecule is also sufficiently hydrophobic to cross T

Melatonin and N-acetylserotonin inhibit leukocyte rolling and adhesion to rat microcirculation

The hormone melatonin produced by the pineal gland during the daily dark phase regulates a variety of biological processes in mammals. The aim of this study was to determine the effect of melatonin and its precursor N-acetylserotonin on the microcirculation during acute inflammation. Arteriolar diameter, blood flow rate, leukocyte rolling and adhesion were measured in the rat microcirculation in situ by intravital microscopy. Melatonin alone or together with noradrenaline did not affect the arteriolar diameter or blood flow rate. Melatonin inhibited both leukocyte rolling and leukotriene B(4) induced adhesion while its precursor N-acetylserotonin inhibits only leukocyte adhesion. The rank order of potency of agonists and antagonist receptor selective ligands suggested that the activation of MT(2) and MT(3) melatonin binding sites receptors modulate leukocyte rolling and adhesion, respectively. The effect of melatonin and N-acetylserotonin herein described were observed with concentrations in the range of the nocturnal surge, providing the first evidence for a possible physiological role of these hormones in acute inflammation.

Circadian rhythm in experimental granulomatous inflammation is modulated by melatonin

Lopes C, deLyra JL, Markus RP, Mariano M. Circadian rhythm in experimental granulomatous inflammation is modulated by melatonin. J. Pineal Res. 1997; 23:72–78.

Interaction between the adrenal and the pineal gland in chronic experimental inflammation induced by BCG in mice

Abstract:Objective: To investigate the adrenal gland influence on diurnal rhythm of chronic inflammation induced by BCG in mice and its interaction with the pineal gland.¶Methods: C57Bl/6 mice were injected with BCG in the footpad and maintained in a 12/12 h light-dark cycle. All the experimental manipulations were done after 20-45 days. Paw swelling was measured every 4 h for 48 or 72 h and decomposed by Fourier transformation. Vascular permeability was evaluated by Evans Blue overflow, in mice killed at midday or midnight. 6-Sulphatoxymelatonin urine concentration was determined by radioimmunoassay in samples taken during the dark or light phase.¶Results: Adrenalectomy or metyrapone treatment abolished the paw swelling diurnal rhythm, the nocturnal reduction in vascular permeability, and the nocturnal increase in 6-sulphatoximelatonin in the urine. Nocturnal administration of melatonin to adrenalectomized mice restored the paw swelling diurnal variation and the reduction of vascular permeability of the inflamed paw.¶Conclusion: Adrenal cortical hormones are important for the maintenance of the diurnal rhythm of chronic inflammation (paw swelling and vascular permeability), probably by promoting a nocturnal surge of melatonin, which is the hor-mone that modulates the diurnal variation of chronic inflammation.¶

Pinealectomy-associated decrease in ribosomal gene activity in rats

A decrease in ribosomal gene activity is an essential feature ofthe aging process as it was observed in Alzheimers disease, inelderly Downs patients and in elderly healthy people. It is wellknown that aging is also associated with a reduction in melatoninsynthesis. We studied 24 male Wistar rats cytogenetically, byusing Ag-stained NOR (6 three-month-old rats underwent pinealectomyand were studied after 20 days; 6 control rats of the same age;6 three-month-old rats underwent pinealectomy and were studied after8 months; 6 control rats of the same age). Our resultsindicate that the absence of the pineal gland leads to adecrease in NOR activity. Further studies are necessary todetermine if pinealectomy in rats could provide an animal modelfor aging.

Cinética e mecanismo da reação de auto-oxidação de S(IV) catalisada por íons metálicos de transição

The oxidation process of sulfur (IV) species (SO2, HSO3- e SO32-) by oxygen, catalysed by trace metal ion and complexes, can play an important role in atmospheric, analytical and bioinorganic chemistry. An overview of the most important reactions in these fields is presented. A fascinating redox cycling of the metal ions and complexes during such autoxidation process was revealed by the combination of kinetics and coordination chemistry studies.

Potentiometric Study of Acetate Complexes of Lanthanum (III)

Abstract The stability constants of La(III) - acetate complexes in aqueous medium were determined by a potentiometric method, using a glass electrode, at (25.0±0.1)°C and ionic strength 1.00 M (NaClO4). Four mononuclear stepwise complexes were detected with the Ledens graphical method. Matrix solutions of weighted simultaneous equations with Fronaeus function data lead to the following overall stability constants: β1 = (34.4 ± 0.1) L.mol−1, β2 = (274 ± 1) L2.mol−2, β3 = (464 ± 5) L3.mol−3, β4 = (1.93 ± 0.03)×103 L4.mol−4. A marked increase in affinity for the fourth acetate species suggests a change of configuration after the third species.

A COMPARISON OF CARBOXYLATE COMPLEXES OF LANTHANUM (III): FORMATE, ACETATE AND PROPIONATE

Abstract The stability constants of La(III)-formate and La(III)-propionate complexes in aqueous medium were determined by a potentiometric method using a glass electrode. The temperature was kept at 25°C and an ionic strength of 1.00 M (NaClO4) was used. Four mononuclear complexes were detected for both systems. The pKa values for the carboxylic acids (formic and propionic) were determined at the same conditions. The final values of the overall stability constants determined by a matrix solution of weighted simultaneous equations were: β1 = (13.2 ± 0.6) L mol−1, β2 = (48 ± 4) L2 mol−2, β3 = (118 ± 15) L3 mol−3, β = (85 ± 15) L4 mol4 for La(III)-formate system and β1 = (42 ± 3) L mol−1, β2 = (299 ± 25) L2 mol−2, β3 = (1201 ± 138) L3 mol−3, β4 = (2527 ± 174) L4 mol−4 for La(III)-propionate system. These data and those for La(III)/acetate from the literature were used to compare the tendency to complex.

Kinetic Studies of the Fe(III)/DI-2-Pyridyl Ketone Benzoylhydrazone Complex Reduction By Sulfite

The reactions of HSO− 3 with Fe(III) in the presence of di-2-pyridyl ketone benzoylhydrazone (DPKBH) have been investigated at 4.2-7.2 pH. The decomposition reaction of Fe(III)/DPKBH has been studied as a function of total sulfite concentration using spectrophotometric techniques. The kinetics are controlled by the equilibrium [FeIII(DPKBH)(H2O)]2+ ⇌ [FeIII(DPKBH)(OH)]++H+, for which the hydrolysis constant was potentiometrically determined as 4.3 x 10-5M, at (25.0 ± 0.1)°C and 1.5 x 10-3M ionic strength. Both of those species undergo sulfite substitution and the significantly more labile species is the aqua complex. The formation constants of [FeIII(DPKBH)(SO3)] are 1.2 x 104 at pH 4.2 and 1.9 x 102M-1 at pH 6.2. The limiting rate constants, k, at high HSO− 3 concentrations are 3.5 x 10-2s-1 and 1.4 x 10-2s-1, respectively, at pH 4.2 and 6.2, I = 1.3 x 10-2M. The results are discussed with reference to the available literature data.