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Notes: The characteristics of ventricular fibrillatory signals vary as a function of the time elapsed from the onset of arrhythmia and the maneuvers used to maintain coronary perfusion. The dominant frequency (FrD) of the power spectrum of ventricular fibrillation (VF) is known to decrease after interrupting coronary perfusion, though the corresponding recovery process upon reestablishing coronary flow has not been quantified to date. With the aim of investigating the recovery of the FrD during reperfusion after a brief ischemic, period, 11 isolated and perfused rabbit heart preparations were used to analyze the signals obtained with three unipolar epicardial electrodes (E1-E3) and a bipolar electrode immersed in the thermostatizfid organ bath (E4), following the electrical induction of VF. Recordings were made under conditions of maintained coronary perfusion (5 min), upon interrupting perfusion (15 mini, and after reperfusion (5 min), FrD was determined using Welch's method. The variations in FrD were quantified during both ischemia and reperfusion, based on an exponential model AFrD = A exp (-t/C). During ischemia ΔFrD is the difference between FrD and the minimum value, while t is the time elapsed from the interruption of coronary perfusion. During reperfusion ΔFrD is the difference between the maximum value and FrD, while t is the time elapsed from the restoration of perfusion, A is one of the constants of the model, and C is the time constant. FrD exhibited respective initial values of 16.20 ± 1.67, 16.03 ± 1.38, and 16.03 ± 1.80 Hz in the epicardial leads, and 15.09 ±1.07 Hz in the bipolar lead within the bath. No significant variations were observed during maintained coronary perfusion. The fit of the FrD variations to the model during ischemia and reperfusion proved significant in nine experiments. The mean time constants C obtained on fitting to the model during ischemia were as follows: El =294.4 ± 75.6, E2 = 225.7 ± 48.5, E3 = 327.4 ± 79.7, and E4 = 298.7 ± 43.9 seconds. The mean values of C obtained during reperfusion, and the significance of the differences with respect to the ischemic period were: El = 57.5 ± 8.4 (P ± 0.01), E2 = 64.5 ± 11.2 (P0.01), E3 = 80.7 ± 13.3 (P 〈 0.01), and E4 = 74.9 ± 13.6 (P 〈 0.0001). The time course variations of the FrD of the VF power spectrum fit an exponential model during ischemia and reperfusion. The time constants of the model during reperfusion after a brief ischemic period are significantly shorter than those obtained during ischemia.

Notes: Abstract: In this report, rat hypothalamic nitric oxide synthase (NOS) activity is shown to be partially inhibited by physiological concentrations of the pineal hormone melatonin. In vitro studies demonstrate that 1 nM melatonin, which approximates the physiological concentration of the hormone at night, significantly inhibited NOS activity. In vivo studies show that administering melatonin or collecting the hypothalamus from animals at night, when endogenous melatonin levels are elevated, results in a significant decrease of NOS activity. Results also show that calmodulin may be involved in this process since its presence in the incubation medium prevents the inhibitory effect of melatonin on NOS activity.

Notes: Abstract: Melatonin binding sites were characterized in rat spleen crude membranes. The specific binding of 2-[125I]iodomelatonin by spleen crude membranes fulfills all the criteria for binding to a receptor site. Thus, binding was dependent on time and temperature, stable, specific, and increased under constant light exposure and after pinealectomy. In competition studies, the specific binding of 2-[125I]iodomelatonin to spleen crude membranes was inhibited by increasing concentrations of native melatonin. Scatchard analysis showed that the data were compatible with the existence of two classes of binding sites: a high affinity site with a Kd of 0.53 nM and a binding capacity of 2.52 pM, and a low-affinity site with a Kd of 374 nM and binding capacity of 820 pM. Moreover, binding of 2-[l25I]iodomelatonin exhibited day-night variations with the highest binding observed late during the light period, and the lowest binding was observed late at night. However, binding of 2-[125I]iodomelatonin to membranes remained high when animals were kept under light exposure at night. Results support the hypothesis of a regulatory role of melatonin on the immune system in which melatonin downregulates its own binding site.

Notes: Abstract: This paper reviews the evidence that supports the hypothesis of the existence of specific binding sites for melatonin on immune cells. These binding sites have been described in human blood lymphocytes and granulocytes, and thymus, spleen, and bursa of Fabricius from different rodents and birds. The dissociation constant values of these binding sites are in the 0.1 -1 nM range, suggesting that melatonin may play a physiological role in lymphocyte regulation. Moreover, melatonin binding sites appear to be modulated by guanine nucleotides. Therefore, in addition to other mechanisms described for the regulation of immune function by melatonin, a direct mechanism of regulation can be involved via binding of melatonin by immunocompetent cells.

Notes: Abstract: Melatonin, the chief secretory product of the pineal gland, is a potent and efficient endogenous radical scavenger. Thus, melatonin was shown to protect different biomolecules, such as DNA, membrane lipids, and cytosolic proteins, from oxidative damage induced by oxygen-derived free radicals. In order to study the protective role of melatonin in hydrogen peroxide (H2O2)-induced DNA damage, U-937 cells were treated with different concentrations of H2O2, either in the presence or absence of melatonin, and DNA damage was assessed using the cytokinesis-block micronucleus technique. Melatonin diminished H2O2-induced micronuclei production both in short and long treatments. Additionally, melatonin concentrations higher than 1 μM were capable of protecting cells from spontaneous micronuclei production. These data suggest that melatonin, an endogenous antioxidant and nontoxic compound, may have an important role in protecting cells from genetic damage due to free radicals, supporting the idea of this hormone as a possible therapeutic agent in preventing aging and age-related diseases.

Notes: Abstract: The outer hair cells of the organ of Corti transform sound into electrical signals, beginning the nervous auditive process. These cells produce acoustic emissions when working routinely, known as otoacoustic emissions. Otoacoustic emissions (OAEs) are recorded from the hearing duct through a probe which incorporates a sound source and a sensitive microphone. On the other hand, the cochlea produces oxygen-derived free radicals and nitric oxide, in addition, melatonin is present in the cochlea. The authors have studied the influence of melatonin or an antioxidant mixture (alpha-tocopherol acid succinate, ascorbic acid, glutathione, and N-acetylcysteine) on the postmortem activity of the outer hair cells of the organ of Corti of the rat, measuring distortion product otoacoustic emissions. Control rats showed postmortem distortion product otoacoustic emissions for about 2 min when sacrificed by decapitation, and for about 3 min when sacrificed by chloroform inhalation. Melatonin prolonged the postmortem activity 3.5 times when the animals were sacrificed by decapitation, and 7 times when animals were sacrificed by chloroform inhalation. Similar results were obtained with the antioxidant mixture. Results show that melatonin and other antioxidants have, in general, a protective role on the postmortem activity of the outer hair cells of the organ of Corti.

Notes: : In this paper, we show for the first time, a nyctohemeral rhythm in serum total antioxidant status (TAS) in rats which parallels the 24-H melatonin cycle. Both TAS and melatonin in rat serum exhibited 24 hr variations with nocturnal peak values at 05.00 hr and low basal values during the day. When rats were maintained under light exposure (〉500 lux) from 20.00 h to 05.00 hr, serum TAS was significantly reduced when compared with control rat killed in darkness. Moreover, when animals were maintained under continuous light exposure for 5 days and killed at 05.00 hr, serum TAS exhibited an additional decrease when compared with control rats. Since administering exogenous melatonin also increased TAS in the rat serum, results suggest that melatonin may be relevant in terms of participating in the antioxidative capacity of the rat serum.

Notes: : In this paper, we summarize the results of in vitro studies showing that physiological concentrations of melatonin inhibit the norepinephrine-induced activation of prostaglandin E2 (PGE2) and cyclic AMP production in rat medial basal hypothalamus (MBH). Interestingly, a concentration of melatonin as low as 1 nM, which is roughly equivalent to the nocturnal serum physiological concentration of the hormone in the rat, significantly inhibit PGE2 and cyclic AMP production in the MBH. The suppressive effect of melatonin may be mediated by an inhibition of nitric oxide synthase (NOS) activity, since the stimulatory effect of sodium nitroprusside (SNP), a spontaneous generator of NO, was not prevented by melatonin. Melatonin also inhibited NOS activity in rat MBH in a dose-dependent manner. The results suggest the existence of a new or an ancillary means by which melatonin may regulate the physiology of the hypothalamus-pituitary unit.

Notes: : While nitric oxide (NO) has been implicated as a mediator of glutamate excitotoxicity after cerebral ischemia/reperfusion, melatonin has been reported to inhibit brain NO production by suppressing nitric oxide synthase. The purpose of the present studies was to determine the effect of exogenous melatonin administration on NO-induced changes during brain ischemia/reperfusion. Indicators of cerebral cortical and cerebellar NO production [nitrite/nitrate levels and cyclic guanosine monophosphate(cGMP)] were used to estimate neural changes after transient bilateral carotid artery ligation followed by reperfusion in adult Mongolian gerbils (Meriones unguiculatus). Results show for the first time that melatonin prevents the increases in NO and cGMP production after transient ischemia/reperfusion in frontal cerebral cortex and cerebellum of Mongolian gerbils. The inhibitory effect of melatonin on NO production and its ability to scavenge free radicals and the peroxynitrite anion may be responsible for the protective effect of melatonin on neuronal structures during transient ischemia followed by reperfusion.