Pineal

The highly psychoactive molecule N,N -dimethyltryptamine (or simply DMT), is found naturally occurring in the brains of humans, mammals, and some other animals, as well as in a broad range of species of the plant kingdom. Although speculative, neurochemical research suggests that DMT may be made in the pineal gland, and it is hypothesised that, as much as melatonin helps activate sleep cycles, DMT activates dreaming, and may also be implicated in other natural visionary states such as mystical experience, near-death experience (NDE), spontaneous psi and psychosis. Amazonian shamans have made use of this chemical for its visionary properties for thousands of years, most likely, and take it as part of a decoction frequently called ayahuasca, which translates from Quechua as “vine of the spirits” or “vine of the dead”. The psychedelic brew is taken because it gives rise to extraordinary mental phenomena that have shamanic and supposed healing qualities, such as synaesthesia, ostensible extra-dimensional percepts, out-of-body experiences, psi experiences and perhaps most commonly, encounters with discarnate entities. When described by independent and seemingly naïve DMT participants the entities encountered tend to vary in detail but often belong to one of a very few similar types, with similar behavioural characteristics. For instance, mischievous shapeshifting elves, preying mantis alien brain surgeons and jewel-encrusted reptilian beings, who all seem to appear with baffling predictability. This opens up a wealth of questions as to the reality (i.e., the ontology) of these entities. The discussion of the phenomenology and ontology of these entities mixes research from parapsychology, ethnobotany and psychopharmacology – the fruits of science – with the foamy custard of folklore, anthropology, mythology, cultural studies and related disciplines. Hopefully however, given the varied readership of this journal, it won’t prove to be a trifle too interdisciplinary.

Abstract:  The pancreas is highly susceptible to the oxidative stress induced by ischemia/reperfusion (IR) injury leading to the generation of acute pancreatitis. Melatonin has been shown to be useful in the prevention of the damage by ischemia-reperfusion in liver, brain, myocardium, gut and kidney. The aim of the study was to evaluate the cytoprotective properties of melatonin against injury induced by IR in pancreas. The obstruction of gastro-duodenal and inferior splenic arteries induced pancreatic IR in male Wistar rats. Melatonin was intraperitoneally administered before or/and after IR injury. The animals were killed at 24 and 48 hr after reperfusion and there were evaluated parameters of oxidative stress (lipoperoxides, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione), glandular endocrine and exocrine function (lipase, amylase, insulin) and cell injury (apoptosis and necrosis). The IR induced a marked enhancement of oxidative stress and impaired pancreatic function. The histological analysis showed that IR induced acute pancreatitis with the accumulation of inflammatory infiltrate, disruption of tissue structure, cell necrosis and hemorrhage. Melatonin administration before or after pancreatic IR prevented all tissue markers of oxidative stress, biochemical and histological signs of apoptosis and necrosis, and restored glandular function. No histological signs of pancreatitis were observed 48 hr after reperfusion in 80% of the animals treated with melatonin, with only a mild edematous pancreatitis being observed in the remaining rats. Preventive or therapeutic administration of melatonin protected against the induction of oxidative stress and tissue injury, and restored cell function in experimental pancreatic IR in rats.

Abstract:  Melatonin (N-acetyl-5-methoxytryptamine) is an efficient free radical scavenger and antioxidant, both in vitro and in vivo. The role of melatonin as an immunomodulator is, in some cases, contradictory. In this study we have investigated the therapeutic efficacy of melatonin in rats subjected to Pelagia noctiluca crude venom (of the familia Pelaguiidae; and genus Pelagia) induced acute paw inflammation. In particular, injection of the venom into the paw of rats elicited an acute inflammatory response characterized by accumulation of fluid containing a large number of polymorphonuclear neutrophils in the paw and subsequent lipid peroxidation. Furthermore, the venom promoted an expression of iNOS, nitrotyrosine and the activation of the nuclear enzyme poly (ADP-ribose) polymerase as determined by immunohistochemical analysis of paw tissues. Administration of melatonin 30 min, 1 and 6 hr after the challenge with the venom, caused a significant reduction in all the parameters of inflammation measured. Thus, based on these findings we propose that melatonin may be useful a treatment of local acute inflammation induced by P. noctiluca crude venom.

Cross-sectional data on urinary 6-hydroxymelatonin sulfate (6-OHMS) excretion in children suggest a constant melatonin secretion during growth. The present longitudinal study concerned, accordingly, the intra-individual stability of melatonin production during childhood and adolescence. Urine samples collected during a longitudinal investigation of healthy white children and adolescents were analyzed. Forty-six boys and 38 girls were chosen for the present study. They had passed 3-15 annual examinations between their 3rd and 18th yr of age. Each examination included the collection of urine over 24 hr. The daily urinary output of 6-OHMS of the overall 621 samples was quantified by enzyme-linked immunosorbent assay. The analyses clearly revealed for the first time that, despite huge inter-individual differences, melatonin production remains constant in one and the same individual during childhood and adolescence. Additionally, neither a significant sex difference was observed nor was the 6-OHMS output affected by season. The dramatic decrease of plasma melatonin levels as described in the literature is mainly related to an increase in body size rather than to decreasing pineal secretion.

COVERS  - WORKING WITH THE SIZE OF THE AETHERS
THAT THE PINEAL IS AN ANU, THUS GOD,
HOW THE DARK SIDE COMMUNICATES WITH THEIR MINIONS
HOW THE PINEAL WORKS AND WHY IT WORKS THAT WAY.
HOW TO ACHIEVE ONENESS DIRECTLY VIA YOUR OWN GLOW.
AND, THAT ORGONE WORKS VERY WELL.

Metal exposure is associated with several toxic effects; herein, we review the toxicity mechanisms of cadmium, mercury, arsenic, lead, aluminum, chromium, iron, copper, nickel, cobalt, vanadium, and molybdenum as these processes relate to free radical generation. Free radicals can be generated in cells due to a wide variety of exogenous and endogenous processes, causing modifications in DNA bases, enhancing lipid peroxidation, and altering calcium and sulfhydryl homeostasis. Melatonin, an ubiquitous and pleiotropic molecule, exerts efficient protection against oxidative stress and ameliorates oxidative/nitrosative damage by a variety of mechanisms. Also, melatonin has a chelating property which may contribute in reducing metal-induced toxicity as we postulate here. The aim of this review was to highlight the protective role of melatonin in counteracting metal-induced free radical generation. Understanding the physicochemical insights of melatonin related to the free radical scavengi...

Abstract:  The antiproliferative and proapoptotic properties of melatonin in human colon cancer cells in culture were recently reported. To address the mechanisms involved in these actions, HT-29 human colon cancer cells were cultured in RPMI 1640 medium supplemented with fetal bovine serum at 37°C. Cell proliferation was assessed by the incorporation of [3H]-thymidine into DNA. Cyclic nucleotide levels, nitrite concentration, glutathione peroxidase and reductase activities, and glutathione levels were assessed after the incubation of these cells with the following drugs: melatonin membrane receptor agonists 2-iodo-melatonin, 2-iodo-N-butanoyl-5-methoxytryptamine, 5-methoxycarbonylamino-N-acetyltryptamine (GR-135,531), and the antagonists luzindole, 4-phenyl-2-propionamidotetralin, and prazosin; the melatonin nuclear receptor agonist CGP 52608, and four synthetic kynurenines analogs to melatonin 2-acetamide-4-(3-methoxyphenyl)-4-oxobutyric acid, 2-acetamide-4-(2-amino-5-methoxyphenyl)-4-oxobutyric acid, 2-butyramide-4-(3-methoxyphenyl)-4-oxobutyric acid and 2-butyramide-4-(2-amino-5-methoxyphenyl)-4-oxobutyric acid. The results show that the membrane receptors are not necessary for the antiproliferative effect of melatonin and the participation of the nuclear receptor in this effect is suggested. Moreover, the antioxidative and anti-inflammatory actions of melatonin, counteracting the oxidative status and reducing the production of nitric oxide by cultured HT-29 cells seem to be directly involved in the oncostatic properties of melatonin. Some of the synthetic kynurenines exert higher antiproliferative effects than melatonin. The results reinforce the clinical interest of melatonin due to the different mechanisms involved in its oncostatic role, and suggest a new synthetic pathway to obtain melatonin agonists with clinical applications to oncology.

Abstract:  This study investigated whether the induction of inducible nitric oxide synthase (iNOS) produced by acute exercise in rat skeletal muscle could be prevented by melatonin and whether iNOS down-regulation was related to inhibition of nuclear factor kappaB (NF-κB) activation. Male Wistar rats received melatonin i.p. at a dose of 1.0 mg/kg body weight 30 min before being exercised for 60 min on a treadmill at a speed of 25 m/min and a 10% slope. Exercise caused a significant induction of iNOS protein levels and a marked activation of NF-κB that were significantly prevented in rats treated with melatonin. Exercise also resulted in increased IκB kinaseα (IKKα) and phosphorylated IκBα protein levels, whereas IκBα content decreased. These effects were blocked by melatonin administration. The increase in the muscle concentration of thiobarbituric acid reactive substances and in the oxidized/reduced glutathione ratio induced by exercise was partially prevented by melatonin. Our data indicate that melatonin has potent protective effects against damage caused by acute exercise in rat muscle, preventing oxidative stress, NF-κB activation and iNOS over-expression. These findings support the view that melatonin treatment, by abolishing the IKK/NF-κB signal transduction pathway, might block the production of noxious mediators involved in the inflammatory process.

Rodríguez AB, Nogales G, Ortega E, Barriga C. Melatonin controls superoxide anion level: Modulation of superoxide dismutase activity in ring dove heterophils. J. Pineal Res. 1998; 24:9–14. © Munksgaard, CopenhagenRodríguez AB, Nogales G, Ortega E, Barriga C. Melatonin controls superoxide anion level: Modulation of superoxide dismutase activity in ring dove heterophils. J. Pineal Res. 1998; 24:9–14. © Munksgaard, CopenhagenAbstractThe pineal gland and the immune system in mammals and birds are functionally connected, with some recent findings showing that melatonin, the major secretory product of the pineal gland in vertebrates, is a free-radical scavenger and general antioxidant. In birds, heterophils, with their ability to ingest and kill different antigens, play a central role in the host defense mechanism. This in vitro study investigated the possible antioxidant action of melatonin in heterophils isolated from adult male and female ring dove)Streptopelia risoria). The superoxide anion levels (O2−) and the superoxide dismutase (SOD) activity were evaluated as indicators of the metabolic burst of heterophils after ingestion of inert particles (latex beads) at the basal time (0 min) and 15, 30,45, and 60 min of incubation with 100 μM melatonin. The heterophil O2− levels, measured by the nitroblue tetrazolium reduction test, were lower after incubation in the presence of melatonin at all the times studied, a time-dependent effect. Latex beads produced a significant increase in SOD activity, whereas there was a significant decrease in the presence of melatonin. In addition, when heterophils were incubated in the presence of both latex beads and melatonin, the indole appeared to annul the enhancement of SOD activity (U-525nm) produced by latex beads. In conclusion, our findings show that the neurohormone melatonin could be a useful antioxidant.The pineal gland and the immune system in mammals and birds are functionally connected, with some recent findings showing that melatonin, the major secretory product of the pineal gland in vertebrates, is a free-radical scavenger and general antioxidant. In birds, heterophils, with their ability to ingest and kill different antigens, play a central role in the host defense mechanism. This in vitro study investigated the possible antioxidant action of melatonin in heterophils isolated from adult male and female ring dove)Streptopelia risoria). The superoxide anion levels (O2−) and the superoxide dismutase (SOD) activity were evaluated as indicators of the metabolic burst of heterophils after ingestion of inert particles (latex beads) at the basal time (0 min) and 15, 30,45, and 60 min of incubation with 100 μM melatonin. The heterophil O2− levels, measured by the nitroblue tetrazolium reduction test, were lower after incubation in the presence of melatonin at all the times studied, a time-dependent effect. Latex beads produced a significant increase in SOD activity, whereas there was a significant decrease in the presence of melatonin. In addition, when heterophils were incubated in the presence of both latex beads and melatonin, the indole appeared to annul the enhancement of SOD activity (U-525nm) produced by latex beads. In conclusion, our findings show that the neurohormone melatonin could be a useful antioxidant.

In intestinal bowel disease (IBD), immune-mediated conditions exert their effects through various cells and proinflammatory mediators. Recent data support a participation of the endoplasmic reticulum stress and mitochondrial dysfunctions in IBD. Moreover, it is evident that chronic degenerative pathologies, including IBD, share comparable disease mechanisms with alteration in the autophagy mechanisms. Chronic inflammation in IBD exposes these patients to a number of signals known to have tumorigenic effects. This circuitry of inflammation and cancer modifies apoptosis and autophagy, and promotes cellular cycle progression, invasion, and angiogenesis. Melatonin has been shown as a specific antioxidant reducing oxidative damage in both lipid and aqueous cell environments. However, several studies provide further insight into the molecular mechanisms of melatonin action in the colon. In this line, recent data suggest that melatonin modulates autophagy and sirtuin activity. An anti-autophagic property of melatonin has been demonstrated, and it could contribute to its anti-oncogenic activity. Nevertheless, there is no information about whether antitumoral effects of melatonin on colon cancer are dependent on autophagy. Sirtuins have pleiotropic effects on cancer development, being reported both as facilitator and as suppressor of colon cancer development. Sirtuins and melatonin are connected through the circadian clock machinery, and melatonin seems able to correct the alterations in sirtuin activity associated with several pathological conditions. Autophagy and sirtuin activities are linked through 5'AMP-activated protein kinase (AMPK) activation, which switches on autophagy and increases sirtuin. The effect of melatonin on AMPK and the impact of this effect on IBD and colon cancer remain an open question.

A study was carried out to determine possible effects of 60-Hz electromagnetic-field exposure on pineal gland function in humans. Overnight excretion of urinary 6-hydroxymelatonin sulfate (6-OHMS), a stable urinary metabolite of the pineal hormone melatonin, was used to assess pineal gland function in 42 volunteers who used standard (conventional) or modified continuous polymer wire (CPW) electric blankets for approximately 8 weeks. Volunteers using conventional electric blankets showed no variations in 6-OHMS excretion as either a group or individuals during the study period. Serving as their own controls, 7 of 28 volunteers using the CPW blankets showed statistically significant changes in their mean nighttime 6-OHMS excretion. The CPW blankets switched on and off approximately twice as often when in service and produced magnetic fields that were 50% stronger than those from the conventional electric blankets. On the basis of these findings, we hypothesize that periodic exposure to pulsed DC or extremely low frequency electric or magnetic fields of sufficient intensity and duration can affect pineal gland function in certain individuals.