Phosphatidylserine-functionalized liposomes-in-microgels for delivering genistein to effectively treat ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory disease involving ulcers in the colon and rectum. The conventional treatments for UC still have many limitations, such as non-specific release, adverse effects and low absorption, resulting in the poor bioavailability of therapeutic agents. To address these challenges, targeting delivery systems are required to specifically deliver drugs to the colonic site with controlled release. Herein, we present a novel microgel oral delivery system, loaded with liposome nanoparticles (Li NPs) containing a natural anti-inflammatory compound genistein (Gen) into alginate microgels, thereby achieving the targeted release of Gen in the colonic region and ameliorating UC symptoms. Initially, Gen was loaded into phosphatidylserine (PS)-functionalized Li NPs to form Gen@Li NPs with an average size of 245.9 ± 9.6 nm. In vitro assessments confirmed that Gen@Li NPs efficiently targeted macrophages and facilitated the internalization of Gen into cells. To prevent rapid degradation in the harsh gastrointestinal tract, Gen@Li NPs were further encapsulated into alginate microgels through electric spraying technology, forming Gen@Li microgels. In vivo distribution tests demonstrated that Gen@Li microgels possessed long-term retention in the colon and gradual release characteristics compared to Gen@Li NPs. Furthermore, in vivo experiments confirmed that Gen@Li microgels significantly alleviated UC symptoms in mice induced by dextran sulfate sodium salt (DSS) mainly through reducing the expression levels of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) and promoting colonic mucosal barrier repair through upregulation of mucosal protein expression. This study shed light on the potential of utilizing oral administration of natural compounds for UC treatment.

Silica nanoparticles trigger phosphatidylserine exposure in red blood cells and induce thrombosis risk.

Silica nanoparticles (SiNPs) have attracted increasing attention for their health effects due to the increased risk of exposure to human bodies via diverse routes. Considering that SiNPs enter the circulatory system and inevitably encounter red blood cells (RBCs), it is necessary to investigate their risk of causing erythrocytotoxicity. In this study, three sizes of SiNPs (SiNP-60, SiNP-120, and SiNP-200) were tested for their effects on mouse RBCs. The results showed that SiNPs could induce hemolysis, morphological changes, and phosphatidylserine (PS) exposure in RBCs in a particulate size-related manner. Further investigations on the underlying mechanism indicated that SiNP-60 exposure increased intracellular reactive oxidative species (ROS) generation and subsequently caused the phosphorylation of p38 and ERK1/2 in RBCs. The addition of antioxidants or inhibitors of mitogen-activated protein kinase (MAPK) signaling significantly attenuated PS exposure in RBCs and ameliorated SiNP-induced erythrocytotoxicity. Moreover, ex vivo assays using platelet-rich plasma (PRP) showed that SiNP-60-induced PS exposure in RBCs could trigger thrombin-dependent platelet activation. The contrary evidence from the assays of PS blockage and thrombin inhibition further confirmed that SiNP-60-induced platelet activation was dependent on PS externalization in RBCs, concomitantly with thrombin formation. These findings revealed the procoagulant and prothrombotic effects of SiNPs through the regulation of PS externalization in RBCs, and may be of great help in bridging the knowledge gap on the potential cardiovascular hazards of particulate silica from both artificial and naturally occurring origins.

Platelet phosphatidylserine is the critical mediator of thrombosis in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a severe immune-mediated prothrombotic disorder caused by antibodies (Ab) reactive to complexes of platelet factor 4 and heparin. Platelets (PLT) and their interaction with different immune cells contribute to prothrombotic conditions in HIT. However, the exact mechanisms and the role of different PLT subpopulations in this prothrombotic environment remain poorly understood. In this study, we observed that HIT patient Ab induce a new PLT population that is characterized by increased P-selectin expression and phosphatidylserine (PS) externalization. Formation of this procoagulant PLT subpopulation was dependent on engagement of PLT Fc-γ-RIIA by HIT Ab and resulted in a significant increase of thrombin generation on the PLT surface. Using an ex vivo thrombosis model and multi-parameter assessment of thrombus formation, we observed that HIT Ab-induced procoagulant PLT propagated formation of large PLT aggregates, leukocyte recruitment and most importantly, fibrin network generation. These prothrombotic conditions were prevented via the upregulation of PLT intracellular cAMP with Iloprost, a clinically approved prostacyclin analogue. Additionally, the functional relevance of P-selectin and PS was dissected. While inhibition of P-selectin did not affect thrombus formation, the specific blockade of PS prevented HIT Ab-mediated thrombin generation and most importantly procoagulant PLT-mediated thrombus formation ex vivo. Taken together, our findings indicate that procoagulant PLT are critical mediators of prothrombotic conditions in HIT. Specific PS targeting could be a promising therapeutic approach to prevent thromboembolic events in HIT patients.

Phosphatidylserine liposomes containing curcumin inhibit bone loss in osteoporotic rats: A possible synergy through a common signaling pathway.

The present study aimed to investigate the effect of phosphatidylserine liposomes containing curcumin (PSLs-Cur) on the development of osteoporosis induced by glucocorticoids (GCs) in the rat model. PSL-Cur, phosphatidylserine (PSL), curcumin (Cur), and alendronate (AL) drugs as a positive control were administrated orally to evaluate the beneficial effects of 3-week treatments on osteoporotic rats. The biochemical and biomechanical properties of bone parameters as well as gene expression were evaluated in treated rats. Moreover, histomorphometric examinations were performed on the bone tissues of the animals. The results revealed that PSL-Cur oral administration caused a significant improvement in serum markers, mechanical strength, and OPG gene expression rather than PSL or Cur administration in osteoporotic rats. Also, PSL-Cur significantly increased the thickness and volume of cortical and trabecular bone mass in comparison with the untreated osteoporotic group. The results of this study indicated that PSL-Cur had a more inhibitory effect on bone loss induced by GCs compared to AL standard drug. Our findings suggested that PSL-loaded Cur may be an appropriate alternative therapy for glucocorticoid-induced osteoporosis. PRACTICAL APPLICATIONS: Osteoporosis is one of the most serious metabolic chronic diseases that causes fragile bone due to decreased mineral density and microarchitectural deterioration in humans. The osteoprotective effects of curcumin and phosphatidylserine, as a food spice and supplementary diet, respectively, have been shown, previously. However, the low bioavailability of curcumin (Cur) due to its poor absorption, rapid metabolism, and fast systemic elimination, limits its benefits. This deficit can be modified with phosphatidylserine liposome (PSL) formulation that facilitates the gastrointestinal delivery of Cur. Moreover, PSL is known as an osteoprotective agent that may make synergy effect with Cur against GC-induced osteoporosis. In this study, daily oral administration of phosphatidylserine liposomes containing curcumin (PSL-Cur) for 3 weeks, considerably improved biochemical, biomechanical, and gene expression of bone parameters in the treated animals subjected to osteoporosis. PSL-Cur can significantly increase the thickness and volume of cortical and trabecular bone mass as well as the mechanical bone strength in animals. Experimental findings proposed PSL-Cur consumption as a proper and safe supplementary medication in the controlling of bone loss in patients with a high risk of osteoporosis.

Preparation and properties of biocompatible PS-PEG/calcium phosphate nanospheres.

A facile room-temperature method was used to prepare phosphatidylserine (PS)-poly(ethylene glycol) (PEG)/calcium phosphate (CaP) nanospheres (PS-poly(ethylene glycol) methyl ether/CaP nanospheres). Transmission electron microscopy (TEM) results confirmed that the PS-PEG/CaP porous nanospheres were spherical with a diameter of 8-12 nm. X-ray and thermo-gravimetric analysis (TGA) results also confirmed that the PS-PEG micelle was packed in the CaP shell. PS-PEG/CaP nanospheres exhibited little effect on the hemolysis, coagulation characteristics of blood and inflammatory response, demonstrating a negligible cytotoxicity response in LO2 liver cells. Experiments performed in zebrafish demonstrated that the PS-PEG/CaP nanospheres had a long circulatory residence time and did not induce apoptosis in zebrafish. Taken together, these results suggest that the PS-PEG/CaP nanospheres have great potential to be used as a drug carrier.

Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study.

BACKGROUND: The present study is an open-label extension (OLE) aimed at evaluating the effect of 100 mg/day of phosphatidylserine enriched with docosahexaenoic acid (PS-DHA) on cognitive performance in nondemented elderly individuals with memory complaints. METHODS: From the participants who completed the core study, 122 continued with a 15-week OLE. Efficacy was assessed using a computerized tool and the Clinical Global Impression of Change (CGI-C) rating scale. RESULTS: A significant improvement in sustained attention and memory recognition was observed in the PS-DHA naïve group, while the PS-DHA continuers maintained their cognitive status. Additionally, a significant improvement in CGI-C was observed in the naïve group. CONCLUSIONS: The results demonstrate that consumption of 100 mg/day of PS-DHA might be associated with improving or maintaining cognitive status in elderly subjects with memory complaints.

Taxol(®)-induced phosphatidylserine exposure and microvesicle formation in red blood cells is mediated by its vehicle Cremophor(®) EL.

AIM: The conventional clinical formulation of paclitaxel (PTX), Taxol®, consists of Cremophor® EL (CrEL) and ethanol. CrEL-formulated PTX is associated with acute hypersensitivity reactions, anemia and cardiovascular events. In this study, the authors investigated the effects of CrEL-PTX on red blood cells (RBCs) and compared these with the effects observed after exposure to the novel nanoparticle albumin-bound PTX, marketed as Abraxane®. RESULTS: The authors demonstrate that CrEL is primarily responsible for RBC lysis and induction of phosphatidylserine exposure. Phosphatidylserine-exposing RBCs showed increased association with endothelial cells in culture. The authors also identified CrEL as being responsible for vesiculation of RBCs. This is the first time that excipients have been shown to be involved in microvesicle formation. Microvesicles were taken up by endothelial cells. CONCLUSION: These results offer new insights into the side effect profile of Taxol, which is likely to have implications for patients with erythrocyte disorders. Abraxane did not induce any of these effects on RBCs, indicating that the choice of excipients can have a pronounced influence on the efficacy and side effects of drug molecules.

Safety of phosphatidylserine containing omega3 fatty acids in ADHD children: a double-blind placebo-controlled trial followed by an open-label extension.

OBJECTIVE: To evaluate the safety of phosphatidylserine (PS) enriched with omega3 fatty acids, mainly eicosapentaenoic (PS-Omega3) in children with attention-deficit hyperactivity disorder (ADHD). METHODS: Two hundred children diagnosed with ADHD were randomised to receive either PS-Omega3 (300mg PS-Omega3/day) or placebo for 15 weeks. One hundred and fifty children continued into an open-label extension for an additional 15 weeks in which they all consumed PS-Omega3 (150mg PS-Omega3/day). Standard blood biochemical and haematological safety parameters, blood pressure, heart rate, weight and height were evaluated. Adverse events and the Side Effect Rating Scale were also assessed. RESULTS: One hundred and sixty-two participants completed the double-blind phase. No significant differences were noted between the two study groups in any of the safety parameters evaluated. One hundred and forty participants completed the open-label phase. At the end of this phase, no significant changes from baseline were observed in any of the studied parameters among participants who consumed PS-Omega3 for 30 weeks. CONCLUSIONS: Study results demonstrate that consumption of PS-Omega3 by children with ADHD, as indicated in a 30-week evaluation period, is safe and well tolerated, without any negative effect on body weight or growth.

The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extension.

OBJECTIVE: To study the efficacy and safety of phosphatidylserine (PS) containing Omega3 long-chain polyunsaturated fatty acids attached to its backbone (PS-Omega3) in reducing attention-deficit/ hyperactivity disorder (ADHD) symptoms in children. METHOD: A 15-week, double-blind, placebo-controlled phase followed by an open-label extension of additional 15 weeks. Two hundred ADHD children were randomized to receive either PS-Omega3 or placebo, out of them, 150 children continued into the extension. Efficacy was assessed using Conners' parent and teacher rating scales (CRS-P,T), Strengths and Difficulties Questionnaire (SDQ), and Child Health Questionnaire (CHQ). Safety evaluation included adverse events monitoring. RESULTS: The key finding of the double-blind phase was the significant reduction in the Global:Restless/impulsive subscale of CRS-P and the significant improvement in Parent impact-emotional (PE) subscale of the CHQ, both in the PS-Omega3 group. Exploratory subgroup analysis of children with a more pronounced hyperactive/impulsive behavior, as well as mood and behavior-dysregulation, revealed a significant reduction in the ADHD-Index and hyperactive components. Data from the open-label extension indicated sustained efficacy for children who continued to receive PS-Omega3. Children that switched to PS-Omega3 treatment from placebo showed a significant reduction in subscales scores of both CRS-P and the CRS-T, as compare to baseline scores. The treatment was well tolerated. CONCLUSIONS: The results of this 30-week study suggest that PS-Omega3 may reduce ADHD symptoms in children. Preliminary analysis suggests that this treatment may be especially effective in a subgroup of hyperactive-impulsive, emotionally and behaviorally-dysregulated ADHD children.

Safety of phosphatidylserine containing omega-3 fatty acids in non-demented elderly: a double-blind placebo-controlled trial followed by an open-label extension.

BACKGROUND: Phosphatidylserine (PS) is a naturally occurring phospholipid present in the inner leaflet of mammalian plasma membranes. Administration of PS extracted from bovine cortex (BC-PS), which contains high levels of omega-3 long chain polyunsaturated fatty acid (LC-PUFA) attached to its backbone, resulted in positive effects on brain functions such as learning and memory. Recently, a novel marine-sourced PS with omega-3 LC-PUFA attached to its backbone was developed (PS-DHA). In the present study, we evaluated the safety profile of the novel PS preparation in non-demented elderly with memory complaints. The efficacy study of this novel formulation indicated that PS-DHA may ameliorate cognitive deficits in non-demented elderly population. METHODS: 157 non-demented elderly participants with memory complaints were randomized to receive either PS-DHA (300 mg PS/day) or placebo for 15 weeks. Standard biochemical and hematological safety parameters, blood pressure and heart rate were evaluated at baseline and endpoint. 122 participants continued into an open-label extension for additional 15 weeks, in which they all consumed PS-DHA (100 mg PS/day) and were evaluated for their blood pressure, heart rate and weight at endpoint. Adverse events were monitored throughout the double-blind and open-label phases. RESULTS: 131 participants completed the double-blind phase. No significant differences were found in any of the tested safety parameters between the study groups, or within each group. 121 participants completed the open-label phase. At the end of this phase, there was a reduction in resting diastolic blood pressure and a slight weight gain among participants who consumed PS-DHA for 30 weeks. CONCLUSIONS: The results of this study indicate that consumption of PS-DHA at a dosage of 300 mg PS/day for 15 weeks, or 100 mg PS/day for 30 weeks, is safe, well tolerated, and does not produce any negative effects in the tested parameters. TRIAL REGISTRATION: clinicaltrials. gov, identifier: NCT00437983.

Phosphatidylserine containing omega-3 fatty acids may improve memory abilities in non-demented elderly with memory complaints: a double-blind placebo-controlled trial.

BACKGROUND: Phosphatidylserine (PS) may have beneficial effects on cognitive functions. We evaluated the efficacy of a novel preparation of PS containing omega-3 long-chain polyunsaturated fatty acids attached to its backbone (PS-DHA) in non-demented elderly with memory complaints. METHODS: 157 participants were randomized to receive either PS-DHA or placebo for 15 weeks. Efficacy measures, assessed at baseline and endpoint, included the Rey Auditory Verbal Learning Test, Rey Complex Figure Test, and a computerized cognitive battery. Clinicians' Global Impression of Change was assessed following 7 and 15 weeks of treatment. RESULTS: 131 participants completed the study although 9 were excluded from the efficacy analysis due to protocol violation. At endpoint, verbal immediate recall was significantly improved in the PS-DHA group compared to the placebo group. Post-hoc analysis revealed that a subset of participants with relatively good cognitive performance at baseline had significant treatment-associated improvements in immediate and delayed verbal recall, learning abilities, and time to copy complex figure. These favorable results were further supported by responder analysis. CONCLUSIONS: The results indicate that PS-DHA may improve cognitive performance in non-demented elderly with memory complaints. Post-hoc analysis of subgroups suggests that participants with higher baseline cognitive status were most likely to respond to PS-DHA. The results of this exploratory study should be followed up by additional studies aimed at confirming the present tentative conclusions.

Effects of Danshensu on maternal syndrome in phosphatidylserine/phosphatidylcholine microvesicle induced-mouse model: is it a candidate for preeclampsia remedy?

BACKGROUND: Up to date, there is few satisfactory pharmacotherapy, except for aspirin and heparin, to stop the preeclampsia progression. Although the mechanism of preeclampsia is poorly understood, it has been proven to be associated with coagulation activation. Researches on prophylactic and therapeutic application of anticoagulants may benefit the clinical aspects of preeclampsia individuals. This study aimed to evaluate the effects of Danshensu on maternal syndrome in phosphatidylserine/phosphatidylcholine (PS/PC) microvesicle induced-mouse model. METHODS: Sixty-six preeclampsia-like pregnant mice, induced by PS/PC microvesicle administration, were randomly divided into six groups. From days 5.5 to 16.5 of pregnancy, each group was respectively treated as follows: a) mice in group C (n = 12, control group) were injected with 100 microl of filtered phosphate-buffered saline into the tail vein every day; b) group PE (n = 15, preeclampsia model group) were injected in the same way with 100 microl of filtered PS/PC vesicle suspension; c) group H (n = 9, group treated with heparin) were injected with 1 unit heparin together with PS/PC vesicle suspension; d) group A (n = 10, group treated with aspirin) were injected with 20 microg/g aspirin-DL lysine as well; e) group LD (n = 10, group treated with low-dose Danshensu) were injected with 10 microg/g Danshensu; and f) group HD (n = 10, group treated with high-dose Danshensu) were injected with 30 microg/g Danshensu. Systolic blood pressure, total urinary protein levels, blood tests for some hemostatic function parameters (mean platelet counts, plasma antithrombin III activity (AT-III), D-D dimmer levels, and thrombin time), fibrin deposition by phosphotungstic acid hematoxylin staining, and thrombomodulin expression by immunohistochemistry staining in placentas were examined as indices for maternal syndrome. RESULTS: Heparin showed significant effects on maternal syndrome of preeclampsia such as hypertension and proteinuria, and different doses of Danshensu also presented the certain effects. High-dose Danshensu and aspirin all demonstrated better effects than low-dose Danshensu on decreasing blood pressure to normal level, while high-dose Danshensu demonstrated better effects than aspirin and low-dose Danshensu on decreasing proteinuria to normal level. As to Danshensu's effects on hemostatic function, high- and low-dose Danshensu's marked effects on increasing the plasma AT-III activity were the same as that of aspirin and inferior to that of heparin. High-dose Danshensu's better effect on elevating the platelet counts was superior to low-dose Danshensu and aspirin. Low-dose Danshensu's obvious effect on decreasing D-D levels was close to heparin and superior to high-dose Danshensu and aspirin. High- and low-dose Danshensu's significant effects on reduced thrombin time level are same to heparin. Different anticoagulants all played improvement roles in placental fibrin depositions, but heparin and high-dose Danshensu's roles on lowering thrombomodulin expression in placentas were superior to low-dose Danshensu and aspirin. However, anticoagulant function of high-dose Danshensu was still inferior to heparin. We found long-term use of heparin and aspirin, in spite of low-dose administration, could raise the risk of bleeding such as placental abruption and intestinal hemorrhage. But no any side effect was observed in mice treated with different doses of Danshensu in our study. CONCLUSIONS: Danshensu has proven to be effective and safe in ameliorating the prognosis of maternal syndrome in a preeclampsia mouse model. We suggest long-term provision of low-dose Danshensu in pregnancy, leading to an improvement of preeclampsia syndrome with considerable maternal safety.

Effects of phosphatidylserine supplementation on exercising humans.

Phosphatidylserine (PtdSer) is a ubiquitous phospholipid species that is normally located within the inner leaflet of the cell membrane. PtdSer has been implicated in a myriad of membrane-related functions. As a cofactor for a variety of enzymes, PtdSer is thought to be important in cell excitability and communication. PtdSer has also been shown to regulate a variety of neuroendocrine responses that include the release of acetylcholine, dopamine and noradrenaline. Additionally, PtdSer has been extensively demonstrated to influence tissue responses to inflammation. Finally, PtdSer has the potential to act as an effective antioxidant, especially in response to iron-mediated oxidation. The majority of the available research that has investigated the effects of PtdSer supplementation on humans has concentrated on memory and cognitive function; patients experiencing some degree of cognitive decline have traditionally been the main focus of investigation. Although investigators have administered PtdSer through intravenous and oral routes, oral supplementation has wider appeal. Indeed, PtdSer is commercially available as an oral supplement intended to improve cognitive function, with recommended doses usually ranging from 100 to 500 mg/day. The main sources that have been used to derive PtdSer for supplements are bovine-cortex (BC-PtdSer) and soy (S-PtdSer); however, due to the possibility of transferring infection through the consumption of prion contaminated brain, S-PtdSer is the preferred supplement for use in humans. Although the pharmacokinetics of PtdSer have not been fully elucidated, it is likely that oral supplementation leads to small but quantifiable increases in the PtdSer content within the cell membrane.A small number of peer-reviewed full articles exist that investigate the effects of PtdSer supplementation in the exercising human. Early research indicated that oral supplementation with BC-PtdSer 800 mg/day moderated exercise-induced changes to the hypothalamo-pituitary-adrenal axis in untrained participants. Subsequently, this finding was extended to suggest that S-PtdSer 800 mg/day reduced the cortisol response to overtraining during weight training while improving feeling of well-being and decreasing perceived muscle soreness. However, equivocal findings from our laboratory might suggest that the dose required to undertake this neuroendocrine action may vary between participants.Interestingly, recent findings demonstrating that short-term supplementation with S-PtdSer 750 mg/day improved exercise capacity during high-intensity cycling and tended to increase performance during intermittent running might suggest an innovative application for this supplement. With the findings from the existing body of literature in mind, this article focuses on the potential effects of PtdSer supplementation in humans during and following exercise.

Phosphatidylserine/phosphatidylcholine microvesicles can induce preeclampsia-like changes in pregnant mice.

We established a phosphatidylserine (PS)/phosphatidylcholine (PC) microvesicles-induced preeclampsia-like model in mice. PS/PC were prepared by mixing 80% PC and 20% PS, and suspended in 0.05 M Tris-HCl at a concentration of 10 mg/mL. One hundred microliters of PS/PC (n = 6) and saline as a control (n = 10) were injected in tail veins of Institute of Cancer Research (ICR) mice every day from days 5.5 to 16.5 of pregnancy. Systolic blood pressure (SBP) was measured by means of the tail-cuff method. On day 17.5, the mice were anesthetized by diethyl ether and euthanized with the collapse of the circulation by drawing blood from the heart. The animals were dissected and the fetuses and placentas removed. Fetal weight and placental weight were evaluated. Plasma antithrombin activity (AT), thrombin-antithrombin complex (TAT), platelet counts, and proteinuria were measured on day 17.5. Placentas were fixed in 4% paraformaldehyde for histologic studies. Statistical analysis was evaluated by analysis of variance and Welch's t-test. Mice injected with PS/PC showed a significant elevation in SBP (124 versus 101 mm Hg; p < 0.001), a significant increase in TAT levels (23 versus 6.6 mug/L; p < 0.05), a significant decrease in platelet counts (88 versus 102 x 10 (10)/L; p < 0.05), a decrease in AT, an increase in proteinuria, and a significant reduction in fetal weight (1.2 versus 1.3 g; p < 0.0001) and placental weight (0.13 versus 0.15 g; p < 0.001), compared with controls. Placentas of mice injected with PS/PC showed diffuse fibrin depositions in the labyrinth layer. We have demonstrated that the artificial PS/PC vesicles induce intrauterine growth restriction with elevations of SBP. The elevation of plasma TAT and the diffuse fibrin depositions in the placentas indicate enhanced thrombin formation, and the significant elevations of SBP indicate preeclampsia-like changes that can be induced by hypercoagulation in the placenta.

Safety of soy-derived phosphatidylserine in elderly people.

Phosphatidylserine (PS) is a phospholipid which has been claimed to enhance neuronal membrane function, and can be derived from several sources. Earlier studies used brain cortex derived PS, of which the human tolerability of 300mg daily in 130 patients has been shown. The human tolerability of PS derived from soybean has not been reported, although it is widely sold as a nutritional supplement which may improve cognitive function in the elderly. We report the results of a study of the safety of two dosages of soy-phosphatidylserine (S-PS) in elderly. Subjects were 120 elderly of both sexes who fulfilled the more stringent criteria for age-associated memory impairment; some also fulfilled the criteria for age-associated cognitive decline. Subjects were allocated at random to one of the three treatment groups: placebo, 300 or 600 mg S-PS daily. Standard biochemical and hematological safety parameters, blood pressure, heart rate and adverse events were assessed at baseline, after 6 and 12 weeks of treatment. No significant differences were found in any of the outcome variables between the treatment groups after Bonferonni-Holme correction. In conclusion, soy derived PS is a safe nutritional supplement for older persons if taken up to a dosage of 200 mg three times daily.

Apoptosis as a determinant of atherothrombosis.

Clinical manifestations of atherosclerosis are the consequences of atherosclerotic plaque rupture that triggers thrombus formation. Tissue factor (TF) is a key element in the initiation of the coagulation cascade and is crucial in thrombus formation following plaque disruption. TF activity is highly dependent on the presence of phosphatidylserine (PS), an anionic phospholipid that is redistributed on the cell surface during apoptotic death conferring a potent procoagulant activity to the apoptotic cell. Apoptosis occurs in the human atherosclerotic plaque and shed membrane apoptotic microparticles rich in PS are produced in considerable amounts within the lipid core. These microparticles carry almost all TF activity and are responsible for the procoagulant activity of the plaque. Moreover, luminal endothelial cell apoptosis might be responsible for thrombus formation on eroded plaques without rupture. Apoptosis might also play a major role in blood thrombogenicity via circulating procoagulant microparticles that are found at high levels in patients with acute coronary syndromes.

The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor.

There have been previous reports that supplements of phosphatidylserine (PS) blunted the release of cortisol in response to exercise stress and that it improved mood. The present study extended these observations by considering whether PS supplementation influenced subjective feelings of stress and the change in heart rate when a stressful mental arithmetic task was performed. In young adults, with neuroticism scores above rather than below the median, the taking of 300mg PS each day for a month was associated with feeling less stressed and having a better mood. The study for the first time reports an improvement in mood following PS supplementation in a sub-group of young healthy adults.

Preliminary evaluation of the effect of GABA and phosphatidylserine in epileptic patients.

The effect of the combined administration of gamma-aminobutyric acid (GABA) and phosphatidylserine was evaluated in a pilot study of 42 patients with drug-resistant epilepsy. The group included patients with complex partial seizures, simple partial seizures and absence seizures. Patients with complex partial seizures and simple partial seizures showed no significant improvement; on the other hand, there was a remarkable decrease in absence seizures, linearly related to the dose of GABA and phosphatidylserine. Side effects occurred in 9 patients and were usually mild.