No abstract

We tested the effect of melatonin on membrane fluidity in microsomes of a rat liver model in which lipid peroxidation was induced by the addition of FeCl3, ADP and NADPH. Membrane fluidity was monitored using fluorescence spectroscopy and lipid peroxidation was estimated by quantifying malonaldehyde (MDA)+4-hydroxyalkenals (4-HDA) concentrations following the induction of lipid peroxidation with and without pre-incubation with melatonin (1 μΜ-3 mM). Membrane rigidity increased during induced lipid peroxidation while melatonin reduced in a concentration-dependent manner both membrane rigidity and MDA+4-HDA generation. Melatonin's protective effect may relate to its known ability to scavenge free radicals and function as an antioxidant.© 1997 Federation of European Biochemical Societies.

Duchenne muscular dystrophy (DMD), a lethal disorder characterized by dystrophin absence, courses with chronic inflammation, sarcolemmal damage, and skeletal muscle degeneration. Among the multiple pathogenic mechanisms proposed for DMD, oxidative stress and inflammation are directly involved in the dystrophic process. Unfortunately, there is no current treatment for DMD, and the inflammatory process is an important target for therapies. Based on the antioxidant and anti-inflammatory properties of melatonin, we investigated whether melatonin treatment may reduce the dystrophic process. Ten DMD patients aged 12.8 +/- 0.98 yr, were treated with melatonin (60 mg at 21:00 hr plus 10 mg at 09:00 hr), and plasma levels of lipid peroxidation (LPO), nitrites (NO(x)), interleukin (IL)-1beta, IL-2, IL-6, tumor necrosis factor-alpha, interferon-gamma, and plasma markers of muscle injury, were determined at 3, 6 and 9 months of treatment. Healthy age- and sex-matched subjects were used as controls. The results show a significant increase in LPO, NO(x), and cytokine levels in plasma of DMD patients compared with controls. Melatonin administration reduced these values to control levels at 3 months of treatment, decreasing further 9 months later. In parallel, melatonin also reduced plasma levels of creatine kinase (CK; 50%), lactate dehydrogenase (28%), aspartate aminotransferase (28%), alanine aminotransferase (20%), and myoglobin (13%). These findings strongly support the conclusion that melatonin administration significantly reduced the hyperoxidative and inflammatory process in DMD patients, reducing the muscle degenerative process.

Recent data indicate that melatonin inhibits brain glutamate receptors and nitric oxide production, thus suggesting that it may exert a neuroprotective and antiexcitotoxic effect. Melatonin has been seen to prevent seizures in several animal models and to decrease epileptic manifestations in humans. The lack of response to conventional anticonvulsants in an epileptic child led us to use melatonin in this case. A female child who began to have convulsive seizures at the age of 1.5 months and was diagnosed as having severe myoclonic epilepsy was unsuccessfully treated with different combinations of anticonvulsants, including valproic acid, phenobarbital, clonazepam, vigabatrin, lamotrigin, and clobazam. Melatonin was thus added to the treatment. Imaging studies (CT, SPECT, and MNR), EEG recordings, blood biochemical, and hematological analyses, including measures of the circadian rhythm of melatonin, were made. The child was initially treated with various anticonvulsants. Severe neurological and psychomotor deterioration combined with increased seizure activity showed a lack of response to the treatment. At the age of 29 mon the patient was in a pre-comatose stage at which time melatonin was added to treatment. After 1 month of melatonin plus phenobarbital therapy and for a year thereafter, the child's seizures were under control. On reducing the melatonin dose after this time, however, seizures resumed and the patient's condition was re-stabilized after restoring melatonin. Prior to our attempts to reduce melatonin, all analyses, including EEG recordings and SPECT, were normal. As far as the results of neurological examination are concerned, only mild hypotony without focalization remained. Changes in the therapeutic schedules during the second year of melatonin treatment, including the withdrawal of phenobarbital, did not result in the same degree of seizure control, although progressively the child became satisfactorily controlled. At the present moment the child continues to have mild hypotony and shows attention disorder and irritability. Melatonin has proven to be useful as adjunctive therapy in the clinical control of this case of severe infantile myoclonic epilepsy. The results suggest that melatonin may have a useful role in mechanisms of neuroprotection and also indicate its use in other cases of untreatable epilepsy. Further studies using more patients and placebo-treatment would be beneficial in understanding the potential use of melatonin as a co-therapy in some cases of seizures.

No abstract

The pineal gland classically has been considered as a vestigial and mystic organ. In the last decades, and with the incorporation of new methodologic procedures, it could be proved that it also has physiologic actions that vary depending on the level of the phylogenetic scale. Its best-known secretion, melatonin, has been related to many different actions, such as sleep promotion, control of biologic rhythms, hormonal inhibition, and an inhibiting action on central nervous system regulation mechanisms. In animal experimentation, there are papers even accepting an anticonvulsant effect. In humans, evidence is reduced to few experiences. In addition to this clinical experience, there is other evidence that clearly relates melatonin to convulsive phenomena. This relationship must be mediated by the following mechanisms attributed to melatonin: altered brain GABAergic neurotransmission, its known interaction with benzodiazepinic brain receptors, through tryptophan metabolite activity (kynurenine, kynurenic acid), or even by its efficacy as a free-radical scavenger.

Studies suggest that the bidirectional relationship existent between the gut microbiome (GM) and the central nervous system (CNS), or so-called the microbiome–gut–brain axis (MGBA), is involved in diverse neuropsychiatric diseases in children and adults. In pediatric age, most studies have focused on patients with autism. However, evidence of the role played by the MGBA in attention deficit/hyperactivity disorder (ADHD), the most common neurodevelopmental disorder in childhood, is still scanty and heterogeneous. This review aims to provide the current evidence on the functioning of the MGBA in pediatric patients with ADHD and the specific role of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in this interaction, as well as the potential of the GM as a therapeutic target for ADHD. We will explore: (1) the diverse communication pathways between the GM and the CNS; (2) changes in the GM composition in children and adolescents with ADHD and association with ADHD pathophysiology; (3) influence of the GM on the ω-3 PUFA imbalance characteristically found in ADHD; (4) interaction between the GM and circadian rhythm regulation, as sleep disorders are frequently comorbid with ADHD; (5) finally, we will evaluate the most recent studies on the use of probiotics in pediatric patients with ADHD.

Melatonin ( N-acetyl-5-methoxytryptamine, aMT) is an indoleamine produced by several organs and tissues including the pineal gland. Melatonin (aMT) modulates the activity of the brain, mainly acting on both GABA and glutamate receptors. Previous studies have shown the participation of melatonin in the control of convulsive crises, suggesting that aMT concentration increases during seizures, and that patients with seizures of diverse origins show an alteration of the aMT rhythm. However, what is not known is the duration of the aMT response to seizures, and whether aMT changes during seizures could be a marker of the disease. For this reason, the serum levels of aMT in 54 children with a convulsive crisis, febrile and epileptic, were analyzed during the crisis, as well as at 1 h and 24 hours after the seizure. The results show that aMT significantly increases during the seizure (Day group, 75.64+/-45.91 and Night group, 90.69+/-51.85 pg/mL), with normal values being recovered 1 h later (Day group, 26.33+/-10.15 and Night group, 27.78+/-7.82 pg/mL) and maintained for up to 24 hours, when the circadian variation of aMT returns to the normal acrophase. Due to the interindividual variation of aMT levels among healthy people, a single determination of the indoleamine concentration is not a suitable marker of the existence of a convulsive crisis unless the circadian profile of aMT secretion in the patient is known. The results obtained also support the view that the stimulation of aMT production by the convulsive crisis may participate in the response of the organism against the seizures.