Phosphatidylserine enriched with polyunsaturated n-3 fatty acid supplementation for attention-deficit hyperactivity disorder in children and adolescents with epilepsy: A randomized placebo-controlled trial.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy, which management mostly relies on the usual treatments of ADHD, especially methylphenidate. Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed as an alternative therapeutic approach in ADHD without epilepsy but has never been evaluated in epilepsy-associated ADHD. METHODS: A multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA, in eicosapentaenoic- and docosahexaenoic-acid form, conjugated to a phospholipid vector (PS-Omega3) in children aged >6 and <16-years old, and suffering from any type of epilepsy and ADHD (inattentive or combined type) according to DSM-V. After a 4-week baseline period, patients were allocated (1:1) either to placebo group or to PS-Omega 3 group and entered a 12 week-double-blind treatment period which was followed by a 12 week-open-label treatment period. The primary outcome was the reduction of the ADHD-rating scale IV attention-deficit subscore after 12 weeks of treatment. RESULTS: The study was stopped early because of lack of eligible participants and the expected sample size was not reached. Seventy-four patients were randomized, 44 in PS-Omega3, and 30 in the placebo group. The reduction after 12 weeks of treatment in the inattention subscore of the ADHD-IV scale was -1.57 in the PS-Omega3 group, and -2.90 in the placebo group (p = 0.33, α = 5%). Results were similar after 24 weeks of treatment and for all other ADHD-related secondary outcomes, with no difference between placebo and PS-Omega3. CONCLUSION: Our study remaining underpowered, no formal conclusion about the effect of Ps-Omega3 could be drawn. However, our data strongly suggested that the PS-Omega 3 formulation used in the current study did not improve ADHD symptoms in children with epilepsy. PLAIN LANGUAGE SUMMARY: Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed in ADHD but has never been evaluated in patients with both epilepsy and ADHD. To address this issue, we conducted a multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA in children with epilepsy and ADHD. The study was stopped early because of lack of eligible participants, hampering formal conclusion. However, the evolution of the ADHD symptoms at 12 and 24 weeks did not differ between placebo and PUFA supplementation, strongly suggesting that PUFA did not improve ADHD symptoms in children with epilepsy.

Effect of hydroxyurea on erythrocyte apoptosis in hemoglobinopathy patients.

BACKGROUND: Hydroxyurea (HU) therapy improves the clinical severity of patients with hemoglobinopathies. Few studies have documented some mechanisms of HU, but the exact mechanism of action is unknown. Phosphatidylserine on erythrocytes is responsible for apoptosis. In this study, we investigate the expression of phosphatidylserine on the erythrocytes surface of hemoglobinopathies before and after HU treatment. RESEARCH DESIGNS AND METHODS: Blood samples from 45 thalassemia intermedia and 40 SCA and 30 HbE-b-thalassemia patients were analyzed before and after 3 and 6 months of HU treatment. The profile of phosphatidylserine was determined by flow-cytometry using the Annexin V-RBC apoptosis kit. RESULTS: Hydroxyurea proved effective in improving clinical severity of hemoglobinopathies. After treatment with hydroxyurea, the percentage of phosphatidylserine-positive cells was significantly reduced in all 3 patient groups (p < 0.0001). Correlation analysis using different hematological parameters as independent variables and % phosphatidylserine  as dependent variable showed a negative relationship with HbF, RBC, and hemoglobin in all 3 patient groups. CONCLUSION: Hydroxyurea reduces the expression of phosphatidylserine on erythrocytes, contributing to the beneficial effects of this therapy. We suggest that the use of such a biological marker in conjunction with HbF levels may provide valuable insights into the biology and consequences of early RBC apoptosis.

The study investigated the role of hydroxyurea in reducing the externalization of phosphatidylserine on the surface of the erythrocyte membrane of patients with hemoglobinopathies. In patients treated with hydroxyurea for 3 and 6 months, the percentage of phosphatidylserine exposure on the erythrocyte surface was reduced compared with baseline. The decreased percentage of phosphatidylserine correlated negatively with hematologic parameters such as red blood cell (RBC), hemoglobin, and fetal hemoglobin (HbF) in patients at baseline and after HU therapy. Treatment with hydroxyurea decreases the percentage of PS exposure on the surface of RBCs, contributing to the beneficial effects of this therapy. We, therefore, suggest that the use of such a biological marker on the erythrocyte cell surface in conjunction with HbF levels may provide valuable insights into the biology and consequences of early erythrocyte apoptosis.

Clinical usefulness of nutraceutics with acetyl-L-carnitine, α-lipoic acid, phosphatidylserine, curcumin, C, E and B-group vitamins in patients awaiting for carpal tunnel release during COVID-19 pandemic: a randomized controlled open label prospective study.

BACKGROUND AND AIM OF THE WORK: Carpal Tunnel Syndrome (CTS) is provoked by the compression of the median nerve, leading to nerve ischemia, endoneural edema, venous congestion, and subsequent metabolic alterations. Conservative treatments could be considered. The present study investigates the efficacy of a specific blend of a 600 mg dietary integrator composed of acetyl-L-carnitine, α-lipoic acid, phosphatidylserine, Curcumin, C, E and B1, B2, B6 and B12 vitamins in patients with mild to moderate CTS. METHODS: The present investigation involved the outpatients who were planned to undergo open surgical decompression of the median nerve awaiting surgery from June 2020 and February 2021. CTS surgery has been significantly reduced in our institutions during the COVID-19 pandemic. Patients were randomized into Group A (dietary integration 600 mg twice day for 60 days) and Group B (control group, no drug administration). Clinical and functional improvement was prospectively measured after 60 days Results: One-hundred forty-seven patients completed the study, 69 from group A and 78 from group B. BCTQ was significantly improved with the drug administration, as well as BCTQ symptoms subscale, and the pain. BCTQ function subscale and Michigan Hand Questionnaire was not significantly improved. Ten patients in group A (14.5%) declared that they didn't need further treatment. No major side effects were noticed. CONCLUSIONS: Dietary integration could be considered as an option in patients who could not undergo surgery. Symptoms and pain could improve, but surgery remains the gold standard for recovery of function in mild to moderate CTS.

Caryocar coriaceum Wittm. fruit extracts as Leishmania inhibitors: in-vitro and in-silico approaches.

Leishmaniasis is a group of neglected diseases caused by parasites of the Leishmania genus. The treatment of Leishmaniasis represents a great challenge, because the available drugs present high toxicity and none of them is fully effective. Caryocar is a botanical genus rich in phenolic compounds, which leaves extracts have already been described by its antileishmanial action. Thus, we investigated the effect of pulp and peel extracts of the Caryocar coriaceum fruit on promastigote and amastigote forms of Leishmania amazonensis. Both extracts had antipromastigote effect after 24, 48, and 72 h, and this effect was by apoptosis-like process induction, with reactive oxygen species (ROS) production, damage to the mitochondria and plasma membrane, and phosphatidylserine exposure. Knowing that the fruit extracts did not alter the viability of macrophages, we observed that the treatment reduced the infection of these cells. Thereafter, in the in vitro infection context, the extracts showed antioxidant proprieties, by reducing NO, ROS, and MDA levels. Besides, both peel and pulp extracts up-regulated Nrf2/HO-1/Ferritin expression and increase the total iron-bound in infected macrophages, which culminates in a depletion of available iron for L. amazonensis replication. In silico, the molecular modeling experiments showed that the three flavonoids presented in the C. coriaceum extracts can act as synergistic inhibitors of Leishmania proteins, and compete for the active site. Also, there is a preference for rutin at the active site due to its greater interaction binding strength.Communicated by Ramaswamy H. Sarma.

A comparative study of the effects of phosphatidylserine rich in DHA and EPA on Aß-induced Alzheimer's disease using cell models.

Alzheimer's disease (AD) is an age-dependent, irreversible neurodegenerative disease, and one of the pathological features is amyloid-ß (Aß) deposition. Previous studies have shown that phosphatidylserine (PS) enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exhibited significant effects in preventing and alleviating the progress of AD. However, no studies have focused on the differences in the preventive effects on AD between EPA-PS and DHA-PS. Here, the effects of EPA-PS and DHA-PS on Aß production, Aß-induced neurotoxicity and Aß clearance have been studied. The results show that DHA-PS significantly reduced Aß production in CHO-APP/PS1 cells compared to EPA-PS. Moreover, both EPA-PS and DHA-PS significantly protected the primary hippocampal neurons against Aß-induced toxicity by inhibiting the mitochondrial-dependent apoptotic pathway and phosphorylation of JNK and p38. Compared to DHA-PS, EPA-PS administration significantly improved the Aß phagocytic capacity of BV2 cells. In addition, EPA-PS and DHA-PS significantly promoted the neurite outgrowth of primary hippocampal neurons. These findings might provide dietary guidance for the prevention of AD as well as a reference for the development of related functional foods.

Mini-Review: The Administration of Apoptotic Cells for Treating Rheumatoid Arthritis: Current Knowledge and Clinical Perspectives.

Rheumatoid arthritis (RA) is a chronic immune-mediated disease managed by conventional synthetic drugs, such as methotrexate (MTX), and targeted drugs including biological agents. Cell-based therapeutic approaches are currently developed in RA, mainly mesenchymal stroma cell-based approaches. Early-stage apoptotic cells possess direct and indirect anti-inflammatory properties. During the elimination of dying cells (a process called efferocytosis), specific mechanisms operate to control immune responses. There are compelling evidences in experimental models of arthritis indicating that apoptotic cell administration may benefit joint inflammation, and may even have therapeutic effects on arthritis. Additionally, it has been demonstrated that apoptotic cells could be administered with standard treatments of RA, such as MTX or TNF inhibitors (TNFi), given even a synergistic response with TNFi. Interestingly, apoptotic cell infusion has been successfully experienced to prevent acute graft-vs.-host disease after hematopoietic cell transplantation in patients with hematologic malignancies, with a good safety profile. In this mini-review, the apoptotic cell-based therapy development in arthritis is discussed, as well as its transfer in the short-term to an innovative treatment for patients with RA. The use of apoptotic cell-derived factors, including secretome or phosphatidylserine-containing liposomes, in RA are also discussed.

Phosphatidylserine for the Treatment of Pediatric Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis.

Objective: To examine the evidence for efficacy of phosphatidylserine for symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Methods: Medline, Cochrane Library, and ClinicalTrials.gov were searched from inception through August 2020. Studies of any design that assessed phosphatidylserine supplementation for children aged ≤18 years with a diagnosis of ADHD were included in the systematic review; only randomized clinical trials were included in the meta-analysis. Standardized mean differences and 95% confidence intervals (CIs) were calculated, and the heterogeneity of the studies was estimated using I2. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. Results: Four studies met the inclusion criteria for the narrative review (n = 344) and three for the meta-analysis (n = 216). Results of the meta-analysis showed a statistically significant effect of 200-300 mg/day of phosphatidylserine on symptoms of inattention relative to placebo (effect size [ES] 0.36; 95% CI: 0.07 to 0.64; p = 0.01). The effects of phosphatidylserine on overall symptoms of ADHD (ES 0.76; 95% CI: -0.07 to 1.60; p = 0.07) and hyperactivity-impulsivity (ES 0.24; 95% CI: -0.04 to 0.53; p = 0.09) were not statistically significant. Conclusions: Preliminary evidence suggests that phosphatidylserine may be effective for reducing symptoms of inattention in children with ADHD, although the quality of the evidence is low and additional research in this area is warranted.

Combination therapy of phosphatidylserine liposome with cyclosporine A improves nephrotoxicity and attenuates delayed-type hypersensitivity response.

This study aimed to evaluate the antioxidant capacity of phosphatidylserine liposome (PS) against oxidative stress due to cyclosporine A (CsA) and concurrent administration of PS and CsA on the attenuation of immune response. The effect of oral PS was evaluated on biochemical and oxidative renal markers and histopathology of nephrotic rats receiving CsA. The effect of co-administration of PS with CsA was also assessed on DTH (delayed-type hypersensitivity) reaction of immunized rats. The cytokines production level of IL-2 (Interleukin-2) and IFN-γ (Interferon gamma) was measured in immunized rat's splenocytes. PS treatment significantly (P < 0.05) reduced Cr and BUN of serum and MDA (malondialdehyde) in kidney tissue, and increased SOD (superoxide dismutase) and CAT (Catalase) of kidney tissue in CsA-nephrotic rats. Histopathology data indicated significantly (P < 0.05) nephrotoxicity improvement after 25-day treatment with PS. Furthermore, CsA plus PS administration significantly reduced DTH response and cytokines production of IL-2 and IFN-γ in immunized rats. In conclusion, coadministration of CsA plus PS may overcome oxidative stress and improve the performance of organ transplantation or autoimmune therapy.

Neuroprotective Effect of Bean Phosphatidylserine on TMT-Induced Memory Deficits in a Rat Model.

BACKGROUND: Trimethyltin (TMT) is a potent neurotoxin affecting various regions of the central nervous system, including the neocortex, the cerebellum, and the hippocampus. Phosphatidylserine (PS) is a membrane phospholipid, which is vital to brain cells. We analyzed the neuroprotective effects of soybean-derived phosphatidylserine (Bean-PS) on cognitive function, changes in the central cholinergic systems, and neural activity in TMT-induced memory deficits in a rat model. METHODS: The rats were randomly divided into an untreated normal group, a TMT group (injected with TMT + vehicle), and a group injected with TMT + Bean-PS. The rats were treated with 10% hexane (TMT group) or TMT + Bean-PS (50 mg·kg-1, oral administration (p.o.)) daily for 21 days, following a single injection of TMT (8.0 mg/kg, intraperitoneally (i.p.)). The cognitive function of Bean-PS was assessed using the Morris water maze (MWM) test and a passive avoidance task (PAT). The expression of acetylcholine transferase (ChAT) and acetylcholinesterase (AchE) in the hippocampus was assessed via immunohistochemistry. A positron emission tomography (PET) scan was used to measure the glucose uptake in the rat brain. RESULTS: Treatment with Bean-PS enhanced memory function in the Morris water maze (MWM) test. Consistent with the behavioral results, treatment with Bean-PS diminished the damage to cholinergic cells in the hippocampus, in contrast to those of the TMT group. The TMT+Bean-PS group showed elevated glucose uptake in the frontal lobe of the rat brain. CONCLUSION: These results demonstrate that Bean-PS protects against TMT-induced learning and memory impairment. As such, Bean-PS represents a potential treatment for neurodegenerative disorders, such as Alzheimer's disease.

New Nutraceutical Combination Reduces Blood Pressure and Improves Exercise Capacity in Hypertensive Patients Via a Nitric Oxide-Dependent Mechanism.

Background High blood pressure (BP) has long been recognized as a major health threat and, particularly, a major risk factor for stroke, cardiovascular disease, and end-organ damage. However, the identification of a novel, alternative, integrative approach for the control of BP and cardiovascular protection is still needed. Methods and Results Sixty-nine uncontrolled hypertension patients, aged 40 to 68 years, on antihypertensive medication were enrolled in 2 double-blind studies. Forty-five were randomized to placebo or a new nutraceutical combination named AkP05, and BP, endothelial function, and circulating nitric oxide were assessed before and at the end of 4 weeks of treatment. Twenty-four patients were randomized to diuretic or AkP05 for 4 weeks and underwent a cardiopulmonary exercise test to evaluate the effects of AkP05 on functional capacity of the cardiovascular, pulmonary, and muscular systems. Vascular and molecular studies were undertaken on mice to characterize the action of the single compounds contained in the AkP05 nutraceutical combination. AkP05 supplementation reduced BP, improved endothelial function, and increased nitric oxide release; cardiopulmonary exercise test revealed that AkP05 increased maximum O2 uptake, stress tolerance, and maximal power output. In mice, AkP05 reduced BP and improved endothelial function, evoking increased nitric oxide release through the PKCα/Akt/endothelial nitric oxide synthase pathway and reducing reactive oxygen species production via NADPH-oxidase inhibition. These effects were mediated by synergism of the single compounds of AkP05. Conclusions This is the first study reporting positive effects of a nutraceutical combination on the vasculature and exercise tolerance in treated hypertensive patients. Our findings suggest that AkP05 may be used as an adjunct for the improvement of cardiovascular protection and to better control BP in uncontrolled hypertension.

The Additive Effects of Low Dose Intake of Ferulic Acid, Phosphatidylserine and Curcumin, Not Alone, Improve Cognitive Function in APPswe/PS1dE9 Transgenic Mice.

Alzheimer's disease (AD) is the most common form of dementia and its prevention and treatment is a worldwide issue. Many natural components considered to be effective against AD have been identified. However, almost all clinical trials of these components for AD reported inconclusive results. We thought that multiple factors such as amyloid ß (Aß) and tau progressed the pathology of AD and that a therapeutic effect would be obtained by using multiple active ingredients with different effects. Thus, in this study, we treated ferulic acid (FA), phosphatidylserine (PS) and curcumin (Cur) in combination or alone to APPswe/PS1dE9 transgenic mice and evaluated cognitive function by Y-maze test. Consequently, only the three-ingredient group exhibited a significant improvement in cognitive function compared to the control group. In addition, we determined the amounts of Aß, brain-derived neurotrophic factor (BDNF), interleukin (IL)-1ß, acetylcholine and phosphorylated tau in the mouse brains after the treatment. In the two-ingredient (FA and PS) group, a significant decrease in IL-1ß and an increasing trend in acetylcholine were observed. In the Cur group, significant decreases in Aß and phosphorylated tau and an increasing trend in BDNF were observed. In the three-ingredient group, all of them were observed. These results indicate that the intake of multiple active ingredients with different mechanisms of action for the prevention and treatment of AD.

Phosphatidylserine-microbubble targeting-activated microglia/macrophage in inflammation combined with ultrasound for breaking through the blood-brain barrier.

BACKGROUND AND PURPOSE: Inflammatory reaction plays a crucial role in cerebral ischemia reperfusion (IR) injury. It has been shown that activated microglia long-term existed in cerebral ischemia and induced second injury. Therefore, we hypothesize that prepared phosphatidylserine (PS)-modified microbubbles (PS-MBs) combined with ultrasound-targeted microbubble destruction (UTMD) can safely open the blood-brain barrier (BBB) and target activated microglia for inflammatory area in the later stage of ischemia reperfusion. METHODS: To verify our hypothesis, rat model of IR was established, then the change of activated microglia/macrophage (M/M) and permeability of BBB at 1, 7, 14, and 21 days could be clearly observed post IR. And the activated M/M still can be observed during the whole experiment. RESULTS: The Evans blue extravasation of BBB gradually declined from day 1 to day 21. Compared to the control group, microbubbles containing PS were taken up more by activated M/M (approximately twofold) both in vitro and in vivo. CONCLUSIONS: PS-MBs combined with ultrasound (US) exposure could safely open BBB, and the resulting PS nanoparticles (PS-NPs) could further target activated M/M in the neuroinflammation.

The Exposure of Phosphatidylserine Influences Procoagulant Activity in Retinal Vein Occlusion by Microparticles, Blood Cells, and Endothelium.

The pathogenesis of hypercoagulability in retinal vein occlusion (RVO) is largely unknown. Whether the exposure of phosphatidylserine (PS) and microparticle (MPs) release will affect procoagulant activity (PCA) in RVO needs to be investigated. Objectives. To evaluate PS expression, circulating MPs, and the corresponding PCA in RVO patients. Twenty-five RVO patients were compared with 25 controls. PS-positive cells were detected by flow cytometry. Cell-specific MPs were measured by lactadherin for PS and relevant CD antibody. We explored PCA with coagulation time, purified coagulation complex assays, and fibrin production assays. In RVO, MPs from platelets, erythrocytes, leukocyte, and endothelial cells were increased and the exposure of PS was elevated significantly when compared with controls. In addition, we showed that circulating MPs in RVO patients were mostly derived from platelets, representing about 60-70% of all MPs, followed by erythrocytes and leukocytes. Moreover, PS exposure, ECs, and MPs in RVO lead to shortened clotting time with upregulation of FXa and thrombin formation obviously. Importantly, ECs treated with RVO serum which bounded FVa and FXa explicitly suggested the damage of retinal vein endothelial cells. Furthermore, lactadherin can inhibit the combination between PS and coagulation factors by approximately 70% and then exert an anticoagulant effect. In summary, circulating MPs and exposed PS from different cells may contribute to the increased PCA in patients with RVO. Lactadherin can be used for PS detection and an anticoagulant agent.

A lecithin phosphatidylserine and phosphatidic acid complex (PAS) reduces symptoms of the premenstrual syndrome (PMS): Results of a randomized, placebo-controlled, double-blind clinical trial.

BACKGROUND & AIMS: Many women experience emotional and physical symptoms around the time of ovulation and more so before menstruation interfering with their daily normal life also known as premenstrual syndrome (PMS). Recent observational data suggest that supplementation with Lipogen's phosphatidylserine (PS) and phosphatidic acid (PA) complex (PAS) alleviates these PMS symptoms. The aim of this study was to confirm these observations on the effects of PAS on PMS symptom severity within a controlled clinical trial setting. METHODS: Forty women aged 18-45 years with a diagnosis of PMS were assigned to either take PAS (containing 400 mg PS & 400 mg PA per day) or a matching placebo. The study comprised 5 on-site visits including 1 baseline menstrual cycle followed by 3 treatment cycles. Treatment intake was controlled for by using an electronic device, the Medication Event Monitoring System (MEMS®). Primary outcome of the study was the PMS symptoms severity as assessed by using the Daily Record of Severity of Problems (DRSP). Further, SIPS questionnaire (a German version of the Premenstrual Symptoms Screening Tool (PSST)), salivary hormone levels (cortisol awakening response (CAR) and evening cortisol levels) as well as serum levels (cortisol, estradiol, progesterone and corticosteroid binding globulin (CBG)) were assessed. RESULTS: PMS symptoms as assessed by the DRSP Total score showed a significantly better improvement (p = 0.001) over a 3 cycles PAS intake as compared to placebo. In addition, PAS treated women reported a greater improvement in physical (p = 0.002) and depressive symptoms (p = 0.068). They also reported a lower reduction of productivity (p = 0.052) and a stronger decrease in interference with relationships with others (p = 0.099) compared to the placebo group. No other DRSP scale or item showed significant results. Likewise, the reduction in the number of subjects fulfilling PMS or premenstrual dysphoric disorder (PMDD) criteria as classified by the SIPS did not differ between the PAS and the placebo group. For the biomarkers, the salivary cortisol percentage increase of the CAR was significantly less pronounced in the follicular phase of cycle 4 than in the follicular phase of cycle 1 for subjects taking PAS when compared to subjects taking placebo (p = 0.018). Furthermore, the change of serum cortisol levels between visit 1 and visit 5 differed significantly between groups (p = 0.043). While serum cortisol levels of PAS treated females slightly decreased between visit 1 and visit 5, cortisol levels of females treated with placebo increased. For all other biomarkers, no treatment effects were observed over the 4 cycles study period. Overall, this study confirms that a daily intake of PAS, containing 400 mg PS and 400 mg PA, can be considered as safe. CONCLUSIONS: Results substantiate the efficacy of PAS in reducing symptoms of PMS. In view of the recent inclusion of severe PMS symptoms (PMDD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the positive results of this clinical study merits consideration of developing the PAS complex as a botanical drug for treatment of PMDD. CLINICAL TRIAL REGISTRATION: The study is registered at Deutsches Register Klinischer Studien with the registration number DRKS00009005.

Comparative Study of Different Polar Groups of EPA-Enriched Phospholipids on Ameliorating Memory Loss and Cognitive Deficiency in Aged SAMP8 Mice.

SCOPE: Recent studies have shown that omega-3 PUFAs enriched phospholipids (n-3 PUFA-PLs) have beneficial effects on memory and cognition. However, most reports only attribute the benefit to docosahexaenoic acid (DHA) and pay little attention to eicosapentaenoic acid (EPA). METHODS AND RESULTS: We investigate the effect of EPA-enriched phospholipids on cognitive deficiency in senescence-accelerated prone 8 (SAMP8) mouse. Ten-month-old SAMP8 mice are fed with 2% (w/w) EPA-enriched phosphatidylcholine/phosphatidyl ethanolamine (EPA-PC/PE; EPA:DHA = 46.8:3.01) or 2% EPA-enriched phosphatidylserine (EPA-PS; biosynthesized from EPA-PC/PE) for 8 weeks; we then test the behavioral performances in the Barnes maze test and Morris maze test; the changes of oxidative stress, apoptosis, neurotrophic factors, tau phosphorylation, and Aß pathology are also measured. The results of behavior tests indicate that both EPA-PC/PE and EPA-PS significantly improve memory and cognitive deficiency. It is found that remarkable amelioration of oxidative stress and apoptosis occurs in both EPA-PC/PE and EPA-PS groups. EPA-PS shows more ameliorative effects than EPA-PC/PE on neurotrophic activity by decreasing hyper-phosphorylation of tau and depressing the generation and accumulation of ß-amyloid peptide (Aß). CONCLUSION: These data suggest that EPA-PS exhibits better effects than EPA-PC/PE on ameliorating memory and cognitive function, which might be attributed to the phospholipid polar groups.

The Long-Term Efficacy of a Galactagogue Containing Sylimarin-Phosphatidylserine and Galega on Milk Production of Mothers of Preterm Infants.

AIMS: To investigate the efficacy of a galactagogue, containing Sylimarin-phosphatidylserine (SILITIDIL) and galega consumed in the first month after delivery by mothers of preterm infants, in maintaining milk production during the first 3-6 months after delivery. MATERIALS AND METHODS: Mothers of infants born at gestational age (GA) between 27 and 32 weeks, enrolled in our previous prospective, double-blind, randomized trial and randomly allocated to receive either the galactagogue (GG) or a placebo (PG), were asked about their milk production at 3 and 6 months after delivery. RESULTS: Of the 100 mothers involved in this study, 45 of GG and 44 of PG responded comprehensively to the questions asked. At the third month after delivery, exclusive human milk administration was reported by 22 mothers of GG and 12 mothers of PG (p < 0.05), whereas 29 mothers of GG and 18 mothers of PG were able to administer >50% of the amount of milk assumed. At the sixth month of life, only eight infants received exclusive human milk (six and two of GG and PG, respectively), and the data are not sufficient for a meaningful clinical evaluation. CONCLUSIONS: It is assumed that a galactagogue during the first month after delivery improves human milk administration to preterm neonates after discharge and for the first 3 months of life.

Link between cutaneous infection, stress and depression.

Depression and mood disorders often develop after dermatological conditions which could be primary or secondary to dermatological pathology. The oxidative and psychological stress cause physiological changes in the body. Shift in the methylation pathway, elevated cortisol, lowered neurotransmitter levels and lowered immune system allow infection to penetrate the body and lead to anxiety and depression. Here, a case report of a 20 year old male patient is presented to show how infectious skin lesions, unresponsive to the usual treatment plan, were treated after using a multipronged approach of addressing systemic infection of Escherichia coli, elevated cortisol levels and nutritional imbalances.

Dietary supplements for cognitive impairment.

Alzheimer disease and the other neurodegenerative dementias as yet have no curative treatment. For this reason, the prevention of these conditions and non-pharmacological treatments are important fields of research at present. The Mediterranean diet (rich in fruits, vegetables, legumes, and olive oil, with regular fish consumption and low consumption of dairy products and meats) has been shown to reduce the incidence of mild cognitive impairment (MCI) and, probably, the conversion of MCI to dementia. Vitamins, especially vitamin E and the vitamins of the B group, have also been associated with the prevention of cognitive impairment due to their antioxidant effects. Ginkgo biloba is one of the most widely used supplements in the world for cognitive improvement because of its possible effects as a vasodilator and facilitator of cerebral vascularization. Green tea polyphenols have shown beneficial effects in different diseases, including cognitive impairment. Cerebral aging is associated with changes in the lipid composition of neuronal membranes, so it has been suggested that treatment with phospholipids like phosphatidylcholine and phosphatidylserine could favor cognitive improvement. Similarly, polyunsaturated and omega-3 fatty acids, and docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) supplements are associated with a beneficial effect on cognitive function due to the cumulative summation of factors that ultimately favor membrane permeability and neuronal functioning.

Phosphatidylserine enhances IKBKAP transcription by activating the MAPK/ERK signaling pathway.

Familial dysautonomia (FD) is a genetic disorder manifested due to abnormal development and progressive degeneration of the sensory and autonomic nervous system. FD is caused by a point mutation in the IKBKAP gene encoding the IKAP protein, resulting in decreased protein levels. A promising potential treatment for FD is phosphatidylserine (PS); however, the manner by which PS elevates IKAP levels has yet to be identified. Analysis of ChIP-seq results of the IKBKAP promoter region revealed binding of the transcription factors CREB and ELK1, which are regulated by the mitogen-activated protein kinase (MAPK)/extracellular-regulated kinase (ERK) signaling pathway. We show that PS treatment enhanced ERK phosphorylation in cells derived from FD patients. ERK activation resulted in elevated IKBKAP transcription and IKAP protein levels, whereas pretreatment with the MAPK inhibitor U0126 blocked elevation of the IKAP protein level. Overexpression of either ELK1 or CREB activated the IKBKAP promoter, whereas downregulation of these transcription factors resulted in a decrease of the IKAP protein. Additionally, we show that PS improves cell migration, known to be enhanced by MAPK/ERK activation and abrogated in FD cells. In conclusion, our results demonstrate that PS activates the MAPK/ERK signaling pathway, resulting in activation of transcription factors that bind the promoter region of IKBKAP and thus enhancing its transcription. Therefore, compounds that activate the MAPK/ERK signaling pathway could constitute potential treatments for FD.