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Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men

Authors:
Palmiero Monteleone at University of Salerno
Palmiero Monteleone
Mario Maj at University of Campania "Luigi Vanvitelli"
Mario Maj
L Beinat
L Beinat
L Beinat
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M Natale
M Natale
M Natale
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Abstract

The effect of chronic administration of phosphatidylserine derived from brain cortex on the neuroendocrine responses to physical stress has been examined in a placebo-controlled study in 9 healthy men. Phosphatidylserine 800 mg/d for 10 days significantly blunted the ACTH and cortisol responses to physical exercise (P = 0.003 and P = 0.03, respectively), without affecting the rise in plasma GH and PRL. Physical exercise significantly increased the plasma lactate concentration both after placebo and phosphatidylserine. The results suggest that chronic oral administration of phosphatidylserine may counteract stress-induced activation of the hypothalamo-pituitary-adrenal axis in man.
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of distribution in that case would be because enterohe-
patic recycling was impaired. An alternative explanation
could be competition for tissue binding. Although the
exact basis of the kinetic changes is not known it is impor-
tant to note that there was no evidence of an increase in
adverse effects. Since a recent study Karbwang, unpub-
lished data, has shown that the Cm~ and concentrations of
MQ at 24 and 48 h were significantly higher in patients
with an effective response to treatment compared to those
with recrudescence, the higher blood MQ concentration
in the presence of tetracycline gives encouragement for
use of the combination in multi-drug resistant falciparum
malaria.
The fact that the half-life and MRT were significantly
shorter after tetracycline may have been due to alteration
in the gut flora. This should have no bearing on the clinical
response; indeed a sub-therapeutic concentration would
be present for a shorter period of time.
Acknowledgements. We are grateful to Professor K.T.Harinasuta
and the nursing staff at the Hospital for Tropical Diseases, Bangkok.
The study received financial support from the UNDP/World
Bank/WttO Special Programme for Research and Training in Tropi-
cal Diseases.
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Dr. D.J.Back
Department of Pharmacology and Therapeutics
University of Liverpool
R O. Box i47
Liverpool L69 3BX
UK
Erratum
Blunting by chronic phosphatidylserine administration
of the stress-induced activation
of the hypothalamo-pituitary-adrenal axis in healthy men
E Monteleone 1, M. Maj 1, L. Beinat 2, M. Natale 1, and D. Kemali 1
Institute of Psychiatry, First Medical School, University of Naples, Naples and
2 Fidia Research Laboratories, Abano Terme (Padova), Itaty
Received: May 22, 1991/Accepted in revised form: September 18, 1991
Due to an unfortunate error in Volume 42, Number 4,
April 1992, the citation line of the above article showed
the wrong volume number. It should have read:
Eur J Clin Pharmacol (1992) 42:385-388
We apologize for this error.
... Monteleone et al., 1992;Theron et al., 1984). Testosterone is a key anabolic hormone with numerous physiological capabilities in the human body (Buresh et al., 2009). ...
... Previous studies have mainly focused on how the time of day affects short-term maximal performance in highly trained athletes, students or sedentary participants (Belviranli et al., 2017;Benloucif et al., 2008;Chtourou et al., 2015;Gabriel et al., 1992;Kindermann et al., 1982;Mastaloudis et al., 2001;Miyazaki et al., 2001;Monteleone et al., 1992;Smith et al., 2013;Sousa et al., 2019;Theron et al., 1984;Wayner et al., 1987;Yalcin et al., 2003). To the best of the authors' knowledge, no previous study had focused on the diurnal variation of short-term maximal performance or the biological data of police officers. ...
... There is some controversy about the effects of exercise on the endogenous profile of melatonin secretion. It has been reported that melatonin levels increased (Theron et al., 1984), decreased (Monteleone et al., 1992) or remained unaffected (Miyazaki et al., 2001) by exercise in various studies (Escames et al., 2012). Such discrepancies could be due to differences in lighting conditions and the time of day at which the physical exercise was performed. ...
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The specifics of short-term physical exercise are similar to the immediate reaction demands placed on police officers. Identifying the physiological predisposition to short-term high-intensity exercise in male law enforcement officers will assist in understanding their metabolism and make a significant contribution to a much more personal and individualized workout program. This will improve physical fitness of individual officers, improving their preparedness for such times of emergency. This cross-sectional study was conducted to investigate the responses of hematological (erythrocytes, hemoglobin, hematocrit, leucocytes, monocytes, neutrophils, lymphocytes), hormonal (testosterone, cortisol, melatonin), biochemical (glucose, uric-acid, lactate, creatine-phosphokinase) data to short-term maximal exercise in male police officers ( n = 20). Blood samples were collected before- and after- the running-based anaerobic sprint test (RAST), and biological values were corrected for fluid shifts. Data were mean ± standard deviation of differences (= after minus before RAST). After the RAST, values of cortisol, lactate, neutrophils, lymphocytes, and monocytes increased significantly by 7.01 ± 37.36 mmol/l, 7.55 ± 1.67 mmol/l, 0.17 ± 0.26 10 ³ /µl, 0.61 ± 0.28 10 ³ /µl, and 0.10 ± 0.13 10 ³ /µl, respectively. After the RAST, values of melatonin, uric-acid, creatine-phosphokinase, hemoglobin, and hematocrit decreased significantly by −13.24 ± 4.60 pg/ml, −13.28 ± 14.35 µmol/l, −10.23 ± 10.13 IU/l, −2.01 ± 0.81 g/dl, and −4.46 ± 0.59%, respectively. Biological data of male police officers were affected by sprint test. Understanding changes in biological data following short-term maximal exercise can further assist in a better understanding of anaerobic metabolism, which will be helpful to find available methods for coaches to quantify training loads.
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... In this study, the downregulation of 2,4-D content resulting from IPC helped prevent the development of movement disorders (Tu et al., 2019). Exogenous PS supplementation has been shown to mitigate the emergency response of serum cortisol and creatine kinase to acute exercise (Monteleone et al., 1990;Monteleone et al., 1992;Fernholz, 2000), maintaining skeletal muscle movement under high-intensity exercise or hypoxic conditions, prolonging the time to fatigue, and ultimately improving exercise performance (Schumacher et al., 2021;Kingsley et al., 2005;Kingsley Mi et al., 2006). However, in our experiment, PS levels decreased, indicating its utilization in coping with emergency responses during IPC and activating relevant mechanisms through preadaptation, which helps to protect the exercise capacity of skeletal muscles. ...
Identification of the serum metabolomic profile for acute ischemic preconditioning in athletes
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Purpose In recent years, ischemic preconditioning (IPC) has emerged as an effective strategy to increase tissue resistance against long-term ischemic damage and has been increasingly integrated into exercise regimens. However, further research is needed to explore the impact of IPC-mediated metabolic alterations from an exercise standpoint to conduct a comprehensive exploration of metabolic alterations and their exercise-related mechanisms during acute IPC. Methods Nontarget metabolomics was performed on blood samples obtained from 8 male athletes both before and after IPC. The studies included the identification of differentially abundant metabolites, analysis of receiver operating characteristic (ROC) curves, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for differentially abundant metabolites, and metabolite set enrichment analysis (MSEA). Results Nineteen differentially abundant metabolites were identified, with increasing levels of five metabolites, such as O-desmethyltramadol and D-gluconate, whereas 14 metabolites, including 9-hydroxy-10e, 12z-octadecadienoic acid (9-HODE), tetradione, 2-hexenal, (2,4-dichlorophenoxy)acetic acid (2,4-D), and phosphatidylserine (PS), decreased. ROC curve analysis revealed an AUC of 0.9375 for D-gluconate. Both KEGG enrichment analysis and MSEA revealed enrichment in the pentose phosphate pathway (PPP). Conclusion This study revealed that PPP, D-gluconate, O-desmethyltramadol, and D-2-aminobutyric acid could be upregulated within 5 min after acute IPC, whereas 2,4-D, PS, 9-HODE, 2-hexenal, and tetradinone could be downregulated. These identified metabolites show promise for improving physical functional status and could be harnessed to enhance athletic performance.
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... Oral supplement has been becoming the choice for administration of humans with exogenous PS. The oral administration of BC-PS 800 mg/ day for 10 days was demonstrated to significantly attenuate plasma cortisol concentrations in healthy inactive males [30]. Enhancing the higher brain functioning with PS supplement is suggested to employ lower daily doses (<500 mg/day) for longer duration. ...
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... Baumeister et al. [35] demonstrated its ability to restore cognitive performance and cortical activity in humans experimentally subjected to stress. Monteleone et al. [36] caused physical stress in humans using a stationary bicycle and showed that the previous administration of phosphatidylserine was able to reduce the organic response to stress with a reduction in adrenocorticotropic hormone (ACTH) and cortisol production, an effect similar to that obtained by the same authors when they tested the chronic administration of this nutrient [37]. More et al. [38] demonstrated the positive effects of phosphatidylserine obtained from soy lecithin on various aspects of Alzheimer's disease, including memory, cognition, daily activities, and mood. ...
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Introduction The brain is the most complex organ in the human body, with a high and constant demand for inputs. Adequate nutrition is essential for the complete functioning of the brain, not only due to the energy supply, mainly from carbohydrates, but also due to the adequate supply of other macronutrients and micronutrients for the synthesis of neurotransmitters and protein components. Vitamins, minerals, and other components of the diet also constitute the so-called “neuro-nutrients”. Objective It was to develop a systematic review to highlight key neuro-nutrients and clinical studies that direct strategies for adequate nutritional status. Methods The rules of the Systematic Review-PRISMA Platform were followed. The research was carried out from October 2021 to February 2022 and developed based on Scopus, PubMed, Science Direct, Scielo, and Google Scholar. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results A total of 234 articles were found and 167 articles were evaluated in full, and 118 were included and evaluated in the present study. According to the GRADE instrument, most studies (>50%) followed a controlled clinical study model and had a good methodological design. The overall assessment resulted in 54 studies with a high risk of bias to the small sample size. The most important macronutrients in neuro-nutrition are phosphatidylserine and tryptophan. Micronutrients are methyl folate, vitamins B6 and B12, magnesium, arginine, choline, and niacin. Conclusion The areas of neurology and psychiatry have shown great advances regarding the deepening of knowledge in prophylaxis and pathophysiology, as well as in the treatment of established diseases. The recognition of the role of nutrition as an adjunct to these processes is currently growing. The search in scientific bases for neuro nutrients reveals a great growth of publications related to this theme. In the present text, some of these nutrients were explored to verify the current state of knowledge.
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... The specific mechanism of antidepressant effects of PS is still largely unknown; A previous study demonstrated that coinjected PS with scopolamine, an antagonist of acetylcholine receptors abolished antidepressant effects of PS, indicating that muscarinic acetylcholine receptors are required for antidepressant effects of PS (Koutoku et al., 2005). Other studies have reported that PS treatment inhibits the production of ACTH, reduces the production of plasma cortisol, and then slows down the activation of the hypothalamus-pituitaryadrenal (HPA) axis in the process of MDD (Monteleone et al., 1992;Hellhammer et al., 2004;More et al., 2014). Although PS alleviated depressive behaviors in post-stroke depression mice through the reduction of pro-inflammatory cytokines such as TNF-α (Partoazar et al., 2021); the blood contents of IL1β, TNF-α, and IL6 did not alter in elderly patients with MDD after PS supplementation (Brambilla and Maggioni, 1998). ...
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... Some evidence has indicated that PS supplementation is efficient for attenuating physiological stress and exercise recovery (Fahey and Pearl, 1998;Kingsley et al., 2006a;Starks et al., 2008), but it is not clear the physiological and hormonal response pattern. Monteleone et al. (1992) administered two PS doses (i.e. 400 or 800 mg/day) for 10 days and found the highest dose decreased plasma cortisol concentration in healthy sedentary men. ...
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Quinine has been an effective drug for severe chloroquine-resistant falciparum malaria. However, there has been a decline in the sensitivity of Plasmodium falciparum to quinine. In 1978-1979 the cure rate was 94% compared to 86% in 1979-1980 and 76% in 1980-1981. The combination of quinine and tetracycline has improved the cure rate to 95-100%. However, the mechanism responsible for this has not been identified. We have compared plasma quinine levels on day 2, day 5 and day 7 (before and at 2 hours after dosing) in twenty-one patients with acute falciparum malaria who were treated with quinine alone (8 patients) or quinine in combination with tetracycline (8 patients) or quinine with tetracycline and primaquine (5 patients). All patients who received combination of quinine and tetracycline with or without primaquine responded well to the treatment with no recrudescence. Two patients who were treated with quinine alone had RI responses. Plasma quinine concentrations from the quinine alone group were significantly lower than those obtained from combination groups on days 2, 5 and 7. The minimal plasma quinine levels from quinine alone group were all lower than MIC, ie below 10 micrograms/ml while those obtained from the combination group were higher than MIC for 7 days. The results from the present study suggest that tetracycline has influence on the maintenance of plasma quinine levels above MIC throughout the treatment period. Therefore, this must be one possible explanation for the better cure rate.
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  • Nov 1990
Mefloquine, a quinoline-methanol antimalarial, is effective single dose therapy for all species of malaria infecting humans, including multi-drug-resistant Plasmodium falciparum. It is used both in prophylaxis and treatment. Mefloquine is available either as the hydrochloride salt alone, or in a combined preparation with sulfadoxine and pyrimethamine. There is no parenteral formulation. Several assay methodologies have been developed, but high performance liquid chromatography has been the most used in recent pharmacokinetic studies. These have shown in healthy volunteers that mefloquine is absorbed with a half-life of 1 to 4 hours and a time to peak concentration of 7 to 24 hours (median 16.7 hours). Mean peak blood concentrations have ranged between 50 and 110 (median 83) ng/ml/mg/kg. Estimates of total apparent volume of distribution (Vd/f) have ranged from 13.3 to 40.9 (median 19.2) L/kg, systemic clearance (CL/f) from 0.022 to 0.073 L/h/kg (median 0.026 L/h/kg), and terminal elimination half-life from 13.8 to 40.9 days (median 20 days). Systemic clearance appears to be increased in late pregnancy. In uncomplicated falciparum malaria, peak blood concentrations are 2 to 3 times higher than those in healthy subjects ranging from 112 to 209 (median 144) ng/ml/mg/kg because of contraction in the total apparent volume of distribution. Systemic clearance is usually reduced but elimination rates are increased (possibly because of reduced enterohepatic recycling). Mefloquine absorption appears to be reduced in severe falciparum malaria; plasma protein binding exceeds 98% in both healthy subjects and patients. No important drug interactions have been identified as yet, but the potential for serious interactions with quinine has not been adequately investigated. More studies are needed on the disposition of mefloquine in children.
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In vivo action of phosphatidylserine, amitryptiline and stress on the binding of [3H]imipramine to membranes of the rat cerebral cortex
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  • Feb 1989
  • EUR J PHARMACOL
Liposomes of bovine brain phosphatidylserine and of phosphatidylcholine were prepared and injected i.p. into rats for 5 days. Another group received i.p. injections of amitriptyline in addition to phosphatidylserine. Subgroups of control and phosphatidylserine-injected rats were submitted to an acute swimming stress for 15 min. The number of [3H]imipramine binding sites in the phosphatidylserine-injected rats, decreased 23% whereas there was no change in the phosphatidylcholine-injected rats. The combination of amitriptyline and phosphatidylserine produced a more marked reduction in [3H]imipramine binding (-47%). Control rats undergoing acute stress showed a 30% decrease in [3H]imipramine binding whereas the stress did not significantly change the control values of the phosphatidylserine-treated animals. These findings are discussed in relation to the known action of phosphatidylserine on several neurotransmitter systems and on the potentiation of antidepressant effects.
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Determination of mefloquine in biological fluids using high performance liquid chromatography
Article
  • Apr 1989
  • Southeast Asian J Trop Med Publ Health
A simple, specific and sensitive High Performance Liquid Chromatography (HPLC) method for determination of whole blood of mefloquine has been developed. WR 184806 was used as internal standard, using a two step extraction procedure followed by revers phase HPLC. Acetonitrile and dichloromethane were used as extraction solvents. Octanesulphonic acid was used as an ionpairing reagent. Detection of extracted mefloquine and internal standard was achieved at 222 nm. Calibration curves for mefloquine in whole blood showed linearity with correlation coefficients of 0.9999. The limitation of detection using a 1 ml sample was 50 ng/ml. Recovery of mefloquine varied from 61% to 81%. Due to the very similar behavior of the internal standard during extraction, changes in recovery are of minor importance. Good accuracy and precision were obtained (intra-assay coefficient of variation ranged between 1.8% and 5%; inter-assay coefficient of variation were less than 10% at 100 ng/ml and less than 6% at 1,000 ng/ml). The assay employs a rapid and simple two-step extraction which requires a small sample volume. The low limit of detection of mefloquine and the short retention time make the method suitable for routine analysis of mefloquine.
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