Rosa laevigata Michx. Polysaccharide Ameliorates Diabetic Nephropathy in Mice through Inhibiting Ferroptosis and PI3K/AKT Pathway-Mediated Apoptosis and Modulating Tryptophan Metabolism.

Diabetic nephropathy (DN) is a metabolic disease wherein chronic hyperglycemia triggers various renal cell dysfunctions, eventually leading to progressive kidney failure. Rosa laevigata Michx. is a traditional Chinese herbal medicine. Many studies have confirmed its antioxidative, anti-inflammatory, and renoprotective effects. However, the effects and mechanisms of Rosa laevigata Michx. polysaccharide (RLP) in DN remain unclear. In this study, a DN mouse model was established to investigate the therapeutic effect of RLP on DN mice. Then, nontargeted metabolomics was used to analyze the potential mechanism of RLP in the treatment of DN. Finally, the effects of RLP on ferroptosis and the PI3K/AKT pathway were investigated. The results demonstrated that RLP effectively alleviated renal injury and reduced inflammation and oxidative stress in the kidney. In addition, nontargeted metabolomic analysis indicated that RLP could modulate riboflavin metabolism and tryptophan metabolism in DN mice. Notably, ferroptosis and PI3K/AKT pathway-mediated apoptosis in the kidney were also ameliorated following RLP treatment. In conclusion, this study confirmed that RLP had a significant therapeutic effect on DN mice. Furthermore, RLP treatment modulated tryptophan metabolism and inhibited ferroptosis and PI3K/AKT pathway-mediated apoptosis in the kidney.

Aqueous extract of Polygala japonica Houtt. ameliorated nonalcoholic steatohepatitis in mice through restoring the gut microbiota disorders and affecting the metabolites in feces and liver.

BACKGROUND: Polygala japonica Houtt. (PJ) has been demonstrated with several biological potentials such as lipid-lowering and anti-inflammatory effects. However, the effects and mechanisms of PJ on nonalcoholic steatohepatitis (NASH) remain unclear. PURPOSE: The aim of this study was to evaluate the effects of PJ on NASH and illustrate the mechanism based on modulating gut microbiota and host metabolism. MATERIALS AND METHODS: NASH mouse model was induced using methionine and choline deficient (MCD) diet and orally treated with PJ. The therapeutic, anti-inflammatory, and anti-oxidative effects of PJ on mice with NASH were firstly assessed. Then, the gut microbiota of mice was analyzed using 16S rRNA sequencing to assess the changes. Finally, the effects of PJ on the metabolites in liver and feces were explored by untargeted metabolomics. RESULTS: The results indicated that PJ could improve hepatic steatosis, liver injury, inflammatory response, and oxidative stress in NASH mice. PJ treatment also affected the diversity of gut microbiota and changed the relative abundances of Faecalibaculum. Lactobacillus, Muribaculaceae, Dubosiella, Akkermansia, Lachnospiraceae_NK4A136_group, and Turicibacter in NASH mice. In addition, PJ treatment modulated 59 metabolites both in liver and feces. Metabolites involved in histidine, and tryptophan metabolism pathways were identified as the key metabolites according to the correlation analysis between differential gut microbiota and metabolites. CONCLUSION: Our study demonstrated the therapeutic, anti-inflammatory and anti-oxidative potentials of PJ on NASH. The mechanisms of PJ treatment were related to the improvement of gut microbiota dysbiosis and the regulation of histidine and tryptophan metabolism.

Gut Microbiome-Derived Uremic Toxin Levels in Hemodialysis Patients on Different Phosphate Binder Therapies.

INTRODUCTION: Constipation is prevalent in patients with kidney failure partly due to the use of medication, such as phosphate binders. We hypothesized that serum levels of gut microbiome-derived uremic toxins (UTOX) may be affected by the choice of phosphate binder putatively through its impact on colonic transit time. We investigated two commonly prescribed phosphate binders, sevelamer carbonate (SEV) and sucroferric oxyhydroxide (SFO), and their association with gut microbiome-derived UTOX levels in hemodialysis (HD) patients. METHODS: Weekly blood samples were collected from 16 anuric HD participants during the 5-week observational period. All participants were on active phosphate binder monotherapy with either SFO or SEV for at least 4 weeks prior to enrollment. Eight UTOX (7 gut microbiome-derived) and tryptophan were quantified using liquid chromatography-mass spectrometry. Serum phosphorus, nutritional, and liver function markers were also measured. For each substance, weekly individual levels, the median concentration per participant, and differences between SFO and SEV groups were reported. Patient-reported bowel movements, by the Bristol Stool Scale (BSS), and pill usage were assessed weekly. RESULTS: The SEV group reported a 3.3-fold higher frequency of BSS stool types 1 and 2 (more likely constipated, p < 0.05), whereas the SFO group reported a 1.5-fold higher frequency of BSS stool types 5-7 (more likely loose stool and diarrhea, not significant). Participants in the SFO group showed a trend toward better adherence to phosphate binder therapy (SFO: 87.6% vs. SEV: 66.6%, not significant). UTOX, serum phosphorus, nutritional and liver function markers, and tryptophan were not different between the two groups. CONCLUSION: There was no difference in the gut microbiome-derived UTOX levels between phosphate binders (SFO vs. SEV), despite SFO therapy resulting in fewer constipated participants. This pilot study may inform study design of future clinical trials and highlights the importance of including factors beyond bowel habits and their association with UTOX levels.

Potential Anti-Alzheimer Agents from Guanidinyl Tryptophan Derivatives with Activities of Membrane Adhesion and Conformational Transition Inhibitions.

Guanidinyl tryptophan derivatives TGN1, TGN2, TGN3, and TGN4 were synthesized, and these compounds were shown to possess in vitro inhibitory activity for amyloid aggregation in a previous study. Nevertheless, the influence of the TGN series of compounds on the binding and permeation behaviors of an Aß monomer to the cell membranes was not elucidated. In this study, we investigated the effect of compounds in the TGN series on the behavior of an Aß monomer regarding its toxicity toward the bilayer lipid membrane using molecular dynamics (MD) simulation. MD simulations suggest that TGN4 is a potential agent that can interfere with the movement of the Aß monomer into the membrane. The MM-GBSA result demonstrated that TGN4 exhibits the highest affinity to the Aß1-42 monomer but has the lowest affinity to the bilayer. Moreover, TGN4 also contributes to a decrease in the binding affinity between the Aß1-42 monomer and the POPC membrane. Regarding the results of the binding mode and conformational analyses, a high number of amino-acid residues were shown to provide the binding interactions between TGN4 and the Aß1-42 monomer. TGN4 also reduces the conformational transition of the Aß1-42 monomer by means of interacting with the monomer. The present study presents molecular-level insights into how the TGN series of compounds affect the membrane adsorption and the conformational transition of the Aß1-42 monomer, which could be valuable for the further development of new anti-Alzheimer agents.

[L-tryptophan as dietetic supplement and treatment for hot flashes, astenia, and insomnia in cancer patients]. / Triptófano como suplemento dietético y tratamiento de los sofocos, la astenia y el insomnio en el cáncer.

INTRODUCTION: Introduction: in women with breast cancer and gynecologic cancer, as well as in men with prostate carcinoma, hot flashes, asthenia, and insomnia are common and bothersome symptoms that impair quality of life. Objective: to evaluate the effectiveness of tryptophan intake as a treatment for hot flushes, asthenia, and insomnia in patients with prostate, breast, and uterine cervical cancer. Materials and methods: intervention study without a control group at the HUCA Radiation Oncology Service, from July 2018 to July 2019. A total of 60 patients with prostate, breast, or uterine cervical cancer who had received treatment with radiotherapy and hormone therapy, and who presented with hot flushes, asthenia, and insomnia were included. L-tryptophan was administered at a dose of 3 g per day. Results: a significant increase in serum tryptophan levels at the end of the study (p < 0.001) and a significant decrease in the scores of the study symptoms were reported. Although statistical significance was not found, a significant improvement in each symptom was observed, as well as an improvement in quality of life (p < 0.001). Conclusions: the study suggests that, in patients with breast, prostate, or uterine cervical cancer, and symptoms such as hot flushes, asthenia, and insomnia, the administration of tryptophan as a nutritional supplement is well tolerated, improves quality of life, and is associated with improvement in the scale scores of the symptoms of interest, although no statistically significant relationship with increased blood tryptophan levels was found.

INTRODUCCIÓN: Introducción: tanto en las mujeres con cáncer de mama y cáncer ginecológico como en los hombres con carcinoma prostático, los sofocos, la astenia y el insomnio son síntomas frecuentes y molestos que alteran la calidad de vida. Objetivo: evaluar la eficacia del aporte de triptófano como tratamiento de los sofocos, la astenia y el insomnio en pacientes con cáncer de próstata, de mama y cervicouterino. Materiales y métodos: estudio de intervención sin grupo de control en el Servicio de Oncología Radioterápica del HUCA, en el período de julio de 2018 a julio de 2019. Se incluyeron en total 60 pacientes con cáncer de próstata, de mama y cervicouterino que habían recibido tratamiento con radioterapia y hormonoterapia, y que presentaban sofocos, astenia e insomnio. Se administraron 3 g de L-triptófano al día. Resultados: se reportan un aumento significativo del valor del triptófano sérico al final del estudio (p < 0,001) y una disminución significativa de las puntuaciones de los síntomas estudiados; aunque no hemos hallado ninguna significación estadística entre ellos, sí se aprecia una mejoría significativa de cada uno de los síntomas, así como una mejoría de la calidad de vida (p < 0,001). Conclusiones: el estudio actual sugiere que, en los pacientes con cáncer de mama, de próstata o cervicouterino y síntomas de sofocos, astenia e insomnio, el aporte de triptófano como suplemento nutricional se tolera bien, mejora la calidad de vida y puede asociarse a una mejoría de los valores obtenidos en las escalas de los síntomas referidos, aunque no se demuestra ninguna relación estadísticamente significativa con la elevación del triptófano en sangre.

Treatment with the essential amino acid L-tryptophan reduces masticatory impairments in experimental cerebral palsy.

Purpose Children with cerebral palsy (CP) often exhibit difficulties in feeding resulting from deficits in chewing. This study investigates the therapeutic potential of L-tryptophan (TRI) to reduce deficits in chewing in rats subjected to an experimental model of CP.Methods A total of 80 Wistar albino rats were used. Pups were randomly assigned to 4 experimental groups: Control Saline, Control TRI, CP Saline, and CP TRI groups. The experimental model of CP was based on the combination of perinatal anoxia associated with postnatal sensorimotor restriction of the hind limbs. TRI was administered subcutaneously during the lactation period. Anatomical and behavioral parameters were evaluated during maturation, including body weight gain, food intake, chewing movements, relative weight and the distribution of the types of masseter muscle fibers.Results The induction of CP limited body weight gain, decreased food intake and led to impairment in the morphological and functional parameters of chewing. Moreover, for a comparable amount of food ingested, CP TRI animals grew the most. In addition, supplementation with TRI improved the number of chewing movements, and increased the weight and proportion of type IIB fibers of the masseter in rats subjected to CP.Conclusion These results demonstrate that experimental CP impaired the development of mastication and that TRI supplementation increased masticatory maturation in animals subjected to CP.

Carcinogenesis and Bacillus Calmette-Guérin (BCG) Intravesical Treatment of Non-Muscle-Invasive Bladder Cancer under Tryptophan and Thymine Supplementation.

PURPOSE: Evaluate tryptophan and thymine (TT) impact on carcinogenesis and intravesical BCG bladder cancer treatment. METHODS: After identification of TT in vitro inhibitory effect in multiple cancer cell cultures, bladder cancer animal model was induced by MNU intravesical instillations and randomized into four groups: Control (n = 9), BCG (n = 9), TT (n = 7), and BCG + TT (n = 8). BCG groups received intravesical 106 CFU BCG in 0.2 ml saline for 6 consecutive weeks and TT groups received 1 g/kg (1:1) of TT via daily gavage. After 15 wk of protocol, animals were euthanized and the urinary bladders submitted to histopathology, immunohistochemistry, and Western blotting. RESULTS: Urothelial cancer was identified in 100%, 85.7%, 44.5%, and 37.5% of Control, TT, BCG, and BCG + TT groups, respectively. Cell proliferation marked by nuclear Ki-67 was higher in the Control compared to animals in the other groups (P = 0.03). BCG, TT, and BCG + TT groups showed proliferative cell decline and TLR4/5 labeling increase in the urothelium. BCG decreased the urothelial VEGF labeling, even in TT association. CONCLUSION: TT inhibit urothelial carcinogenesis and potentiate the intravesical BCG in the treatment of bladder cancer by reducing cell proliferation and activating TLRs.

Comparison of the Effect of Tanacethum Parthenium, 5-Hydroxy Tryptophan, and Magnesium (Aurastop) versus Magnesium Alone on Aura Phenomenon and Its Evolution.

None of the clinical trials on migraine conducted thus far have focused on the possibility to modulate the phenomenon of aura. Furthermore, whether proper management of aura results in a better control of the headache phase has been poorly investigated. In the setting of a single-center, pilot, clinical trial, we aimed at comparing the effects of Aurastop (a combination of tanacetum parthenium (150 mg extracted at 0.8% = 1.2 mg di of active parthenolide), griffonia simplicifoila (20 mg of 5-hydroxy tryptophan), and magnesium (185 mg of magnesium pidolatum)) with those of magnesium alone (2.25 grams/tablet, corresponding to 184 mg of Mg++) in the treatment of acute attacks of migraine with aura. Between June 2017 and June 2018, 50 consecutive patients (27/23 male/female; mean age, 31 [18-57] years) with at least 3 episodes of aura per year were included (t 0). Participants were instructed to keep track of the following 4 episodes of migraine with aura (t 1) and invited to assume (1) a tablet of Aurastop at the beginning of the following 2 episodes of aura and (2) a magnesium tablet alone at the occurrence of the third and fourth aura attacks. Forty-eight patients (96.0%) had >50% reduction in aura duration when treated with Aurastop vs. 7 patients (14.0%) when treated with magnesium alone (p < 0.001); 48 patients (96.0%) had >50% reduction of aura-related disability when receiving Aurastop vs. 5 patients (10.0%) when treated with magnesium alone (p < 0.001); however, patients receiving Aurastop did not need to take pain killers in 35% of aura attacks vs. 3% when assuming magnesium (p < 0.001). These results support the hypothesis that Aurastop might be effective in interfering with the phenomenon of aura and provide evidence that the clinical benefit attributable to this combination of molecules might be greater than that obtained with single compounds of proven effect on the biology of migraine.

Does l-Tryptophan supplementation reduce chewing deficits in an experimental model of cerebral palsy?

Children with cerebral palsy commonly present with feeding difficulties that result from multiple orofacial sequelae, especially deficits in mastication. A previous study demonstrated that perinatal protein undernutrition accentuated the chewing impact in an experimental model of cerebral palsy. Therefore, the present study investigated whether nutritional manipulation reversed or minimized the chewing sequelae in cerebral palsy. We emphasized the relevance of evaluating the therapeutic potential of nutrients, especially tryptophan supplementation, to reduce the chewing deficits that are typical of this syndrome. Clarification of the role of nutrients may help in the development of new treatment strategies for these children.

Effect of Tryptophan, Vitamin B6, and Nicotinamide-Containing Supplement Loading between Meals on Mood and Autonomic Nervous System Activity in Young Adults with Subclinical Depression: A Randomized, Double-Blind, and Placebo-Controlled Study.

Tryptophan (TRP), a precursor of serotonin is believed to have an antidepressant effect. The pathway for brain uptake of TRP is shared by other large neutral amino acids; therefore, the best time to take TRP may be between meals. No previous study has, however, designated the time of TRP dosing to improve mood. Further, the effects of TRP on autonomic nervous system (ANS) activity are unclear. This study investigated the effects of TRP, vitamin B6, and nicotinamide-containing supplements loading between meals on mood and ANS activity in depressive young adults. Thirty depressive young adults were randomly allocated to receive TRP, vitamin B6, and nicotinamide-containing supplements or a placebo supplements twice daily between meals for 7 d. Mood was measured using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Profile of Mood States (POMS). ANS activities were analyzed by heart rate variability power spectral analysis. Blood samples were assayed for plasma total TRP concentration. For analysis, TRP and placebo groups were further classified into two subgroups according to CES-D score (mild to moderate vs. severe depressive symptoms). The CES-D score significantly improved following both treatments in the severe depression subgroups, while the POMS depression score was significantly improved only in the TRP severe depression subgroup. There was no significant change in ANS activity or plasma total TRP in any group. TRP, vitamin B6, and nicotinamide-containing supplements loading between meals can quickly improve depressed mood in quite low dose in young adults with severe subclinical depression.

The enhanced antitumour response of pimozide combined with the IDO inhibitor L­MT in melanoma.

Melanoma is one of the most fatal and therapy-resistant types of cancer; therefore, identifying novel therapeutic candidates to improve patient survival is an ongoing effort. Previous studies have revealed that pimozide is not sufficient to treat melanoma; therefore, enhancing the treatment is necessary. Indoleamine 2, 3­dioxygenase (IDO) is an immunosuppressive, intracellular rate-limiting enzyme, which contributes to immune tolerance in various tumours, including melanoma, and inhibition of IDO may be considered a novel therapeutic strategy when combined with pimozide. The present study aimed to assess the antitumour activities of pimozide in vitro, and to investigate the effects of pimozide combined with L­methyl-tryptophan (L­MT) in vivo. For in vitro analyses, the B16 melanoma cell line was used. Cell cytotoxicity assay, cell viability assay, wound­healing assay and western blotting were conducted to analyse the effects of pimozide on B16 cells. Furthermore, B16 cell-bearing mice were established as the animal model. Haematoxylin and eosin staining, immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end-labelling staining, western blotting and flow cytometry were performed to determine the effects of monotherapy and pimozide and L­MT cotreatment on melanoma. The results demonstrated that pimozide exhibited potent antitumour activity via the regulation of proliferation, apoptosis and migration. Furthermore, the antitumour effects of pimozide were enhanced when combined with L­MT, not only via regulation of proliferation, apoptosis and migration, but also via immune modulation. Notably, pimozide may regulate tumour immunity through inhibiting the activities of signal transducer and activator of transcription (Stat)3 and Stat5. In conclusion, the present study proposed the use of pimozide in combination with the IDO inhibitor, L­MT, as a potential novel therapeutic strategy for the treatment of melanoma.

Tryptophan supplementation and serotonin function: genetic variations in behavioural effects.

The neurotransmitter serotonin has a role in affective disorders such as depression and anxiety, as well as sleep, cognitive function and appetite. This review examines the evidence that serotonin-related genotypes may moderate the behavioural effects of supplementation with the serotonin precursor amino acid l-tryptophan (TRP), on which synthesis of serotonin (or 5-hydroxytryptamine; 5-HT) depends. However, 95 % of serotonin is synthesised and used in the periphery, and TRP is also metabolised via non-5-HT routes such as the kynurenine pathway. Moreover, understanding of genotypes involved in regulation of serotonin raises questions over the generalisability of TRP effects on behaviour across individuals with varied serotonergic genotypes. To date, only differences between variants of the 5-HT transporter-linked promoter region (5-HTTLPR) have been investigated in relation to behavioural effects of TRP supplementation. Effects of 5-HTTLPR genotypes are usually compared between the alleles that are either high (L/L') or low (S/S') expressing of mRNA for the 5-HT transporter receptor. Yet, another key genetic variable is sex: in women, the S/S' genotype predicts sensitivity to improved mood and reduced cortisol by TRP supplementation, during stressful challenges, whereas the L/L' genotype protects against stress-induced mood deterioration. In men, the L/L' genotype may confer risk of stress-induced increases in negative affect; there are insufficient data to assess effects on male S/S' genotypes. However, better-powered studies to detect sex by genotype by stress by TRP interactions, as well as consideration of more genotypes, are needed before strong conclusions and recommendations for behavioural effects of TRP treatment can be reached.

Nutritional supplements in depressive disorders.

There is increasing evidence about the role of nutrients in mental health. An adequate intake of nutrients contributes to better overall health and mental health in particular. Major depression is a severe mental illness with a high prevalence for which effective treatments exist but not in all cases the patient’s remission is achieved. Therefore, it is increasingly aimed at optimizing the supply of nutrients necessary for adequate brain functioning as adjunctive therapy to antidepressant treatment in depressive disorders. In this article we review those nutrients that have been related to depression: Omega-3 fatty acids, B vitamins, s-adenosylmethionine, tryptophan, magnesium, zinc and probiotics.

Tryptophan status in autism spectrum disorder and the influence of supplementation on its level.

Recent reports show that the worldwide incidence of autism spectrum disorder (ASD) is dramatically increasing, although ASD etiology and pathogenesis are still far to be fully elucidated. Some dietary-derived essential compounds, such as the amino acid tryptophan, appear to be impaired in patients with ASD. Tryptophan (Trp) plays a significant role in the human organism and serves as a precursor for a wide range of bioactive compounds, including major neurotransmitters. Research indicates that tryptophan might be deficient in subjects with ASD. Deficiency in the tryptophan level can be retrieved by investigating Trp levels or its major metabolite kynurenine in urines. The purpose of the present study is to quantify tryptophan content in urine samples (n = 236) of ASD patients, who underwent a supplemented dietary panel with B vitamins and magnesium, compared to controls (without this diet regimen). The samples were analyzed with gas chromatography-mass spectrometry. Additionally, the correlation between body mass index (BMI) and the level of this amino acid in urine was accomplished. Basic parameters of urine samples were also evaluated. Statistical evaluations in the concentration of tryptophan in ASD patients with different severity of symptoms were reported. A significant difference in tryptophan levels in all groups was observed. Supplementation with B vitamins and magnesium has an influence on the Trp concentration. Furthermore, no correlation between BMI and tryptophan levels was found. These results assess that the Trp level in ASD subjects is critical and that intake of B vitamins and magnesium with diet might influence its metabolic homeostasis.

Mejora del sueño en deportistas: uso de suplementos nutricionales / Sleep improvement in athletes: use of nutritional supplements

El sueño es el estado de reposo físico y mental fundamental en la recuperación del sistema biológico, regulando mecanismos claves y ejerciendo su papel en la homeostasis metabólica. Las recomendaciones lo sitúan en torno a las 8 horas/noche, considerándose que una persona sufre restricción del mismo con tiempos inferiores a 6 horas durante 4 o más noches consecutivas. Éste se ve afectado por diferentes factores ambientales de forma negativa lo que conlleva efectos perjudiciales para la esperanza y la calidad de vida. En el ámbito deportivo, el rendimiento es el factor clave para el éxito en la competición. El sueño es pieza clave en el entrenamiento invisible, jugando un papel fundamental en el rendimiento. Está comprobado que la falta de descanso es desencadenante de una menor capacidad física y de la aparición de trastornos anímicos que dificultan la toma de decisiones. Por ello existen un gran número de investigaciones centradas en estudiar cómo mejorar la calidad y la cantidad del sueño de los atletas a partir de una correcta programación de los entrenamientos y/o una nutrición adecuada, y así minimizar la interferencia o mejorar la fase de conciliación del sueño. La conciliación del sueño, las alteraciones de este los días previos a la competición, el horario de entrenamiento, el estilo de vida del deportista y su influencia en el mismo, la alimentación y la suplementación son los principales temas tratados en esta revisión sobre el sueño en deportistas. Es necesario un mayor número de estudios y un mayor nivel de evidencia para poder conocer y usar las diferentes estrategias que mejoren la calidad del sueño en deportistas

Sleep is the physical and mental resting state which is fundamental for recovery of the biological system, regulating key mechanisms and metabolic homeostasis. It is recommended to sleep around 8 hours/night, and sleep restriction is considered when a person sleeps less than 6 hours during 4 or more consecutive nights. Some environmental factors adversely a ecting sleep will reduce quality of life and may increase mortality risk. Sports performance is obviously a key factor that needs to be successful in a competition period. It is well known that insucient rest reduces physical tness and favors the onset of mood disorders. For that reason, multiple lines of research are focused on nding the best way to improve the quality and quantity of sleep in athletes. It has been found that both nutrition and good training periodization are important to improve the rest and sleep of athletes. To get to sleep and its disruption in the previous days to competition, hour of training, athletes’ lifestyle and its impact, nutrition and supplementation, are the key topics addressed in this review about sleep in athletes. There is an urgent need of more research to understand and use diferent strategies, including nutritional supplements, in improving sleep in athletes

Suplementos nutricionales en trastornos de la conducta alimentaria / Nutritional supplements in eating disorders

Se consideran Trastornos de la Conducta Alimentaria (TCA) a una serie de entidades nosológicas diferenciadas que tienen como nexo común una alteración continuada en la ingesta o bien en la conducta relacionada con la ingesta. Dentro de dicha clasificación destacan los siguientes trastornos: Anorexia Nerviosa (AN) y Bulimia Nerviosa (BN). La AN es un trastorno de curso crónico caracterizado principalmente por una negativa o disminución de la ingesta acompañado de una distorsión de la imagen corporal con el consecuente miedo intenso a la ganancia de peso. Se estima una prevalencia vital en la adolescencia de dicho trastorno de aproximadamente el 0,5-1%1. En la BN la presencia de atracones de comida y la posterior conducta compensatoria (en forma de ejercicio intenso, uso de laxantes, diuréticos...) es lo que prima en el paciente. La prevalencia se estima entre un 2 y un 4% en mujeres jóvenes, iniciándose generalmente en etapas algo posteriores que la AN. Se cree que en su patogenia influyen factores biológicos, psicológicos y ambientales así como una cierta vulnerabilidad genética. Existen distintos tratamientos con eficacia avalada por parte de literatura científica, tanto terapias biológicas como psicológicas, a pesar de ello, nos encontramos con una efectividad parcial de dichas terapias siendo necesaria la búsqueda de nuevas dianas así como de nuevos tratamiento. Aunque la etiopatogenia de los TCA no esté clara, algunas de las disfunciones neurobiológicas encontradas permitirían considerar que la dieta y la administración de nutrientes podría ser relevante en el tratamiento de estos trastornos. Proponemos en este artículo una revisión de nuevos tratamientos enfocados al déficit nutricional (AU)

Eating disorders (EDs) are a series of differentiated nosological entities sharing the common link of a continuous alteration in food intake or in food intake-related behavior. Within this classification, the following disorders are noteworthy: anorexia nerviosa (AN) and bulimia nerviosa (BN). Anorexia nervosa is a chronic disorder characterized mainly by negative or decreased food intake accompanied by a distortion of body image and intense accompanying fear of weight gain. The estimated vital prevalence of this disorder in adolescence is approximately 0.5%-1%.1 The primary feature of BN is the presence of binge eating accompanied by compensatory behavior (in the form of intense exercise and the use of laxatives and diuretics, etc.). The prevalence of BN is estimated to be between 2% and 4% in young women, and it generally starts at somewhat later stages than AN. It is believed that biological, psychological, and environmental factors, as well as genetic vulnerability, influence the pathogenesis of EDs. A variety of therapies exist, both biological and psychological, whose effectiveness is supported by the scientific literature. Nonetheless, we find these therapies only partially effective and new targets as well as new treatments should be sought. Although the etiopathogenesis of EDs is unclear, some of the neurobiological dysfunction found suggests that diet and nutrient supplementation could be relevant in their treatment. We review in this article new treatments focusing on nutritional déficits (AU)

A combination of tryptophan, Satureja montana, Tribulus terrestris, Phyllanthus emblica extracts is able to improve sexual quality of life in patient with premature ejaculation.

OBJECTIVE: The management of patient affected by premature ejaculation (PE) is nowadays not highly satisfactory. Here, we aimed to evaluate the tolerability and efficacy of a combination of tryptophan, Satureja montana, Tribulus terrestris, Phyllanthus emblica extracts in order to improve sexual quality of life in patients with premature ejaculation. MATERIALS AND METHODS: All patients attending to 5 urological centers from January 2015 to March 2015, due to premature ejaculation were enrolled in this study. At the enrolment visit, all subjects underwent self-administered IIEF-5, Male Sexual Health Questionnaire-Ejaculation Disorder (MSHQEjD), PEDT and IELTS (calculated as mean from that perceived by partner and that perceived by patient) and underwent urological visit and laboratory examinations. All patients received one tablet per day of a combination of tryptophan, Satureja montana, Tribulus terrestris, Phyllanthus emblica extracts for 3 months (Group A). After 3 months all patients underwent follow-up visit with the same investigations that have been carried out in the enrolment visit. The results were compared with a cohort of patients enrolled in the same period in another urological center and considered as a control group (Group B). All patients in the control group underwent counseling and sexual behavioral treatment without any pharmacological compound. RESULTS: At the follow-up analysis, significant changes in terms of IELT in the Group A (mean difference: 31.90; p < 0.05) at 3 months and versus Group B at the intergroup analysis (mean difference: 30.30; p < 0.05) were reported. In the group A, significant differences from baseline to last follow- up were observed relative to IIEF-5 (mean difference: 1.04; p < 0.05), PEDT (mean difference: -2.57; p < 0.05) and FSH (mean difference: -16.46; p < 0.05). CONCLUSION: In conclusion, patients affected by PE may significantly benefit from oral therapy with a combination of tryptophan, Satureja montana, Tribulus terrestris, Phyllanthus emblica extracts in terms of IELT and PEDT scores improvement.

[New data on the effectiveness of Tadalafil alone and in combination with NeyroDoz in treating erectile dysfunction associated with secondary premature ejaculation].

AIM: To compare the effectiveness of the phosphodiesterase type 5 inhibitor (PDE-5i) tadalafil alone and in combination with a biologically active dietary supplement (BADS) NeyroDoz, containing the precursors of serotonin in patients with erectile dysfunction (ED) associated with secondary premature ejaculation (SPE). MATERIAL AND METHODS: 105 patients (mean age 36.2+/-9.1 years) with concomitant ED and SPE were included in a prospective study and divided into 2 groups. The patients of group 1 (n=47) received PDE-5i 5 mg daily for 1 month. In patients of group 2 (n=58) PDE-5i was co-administered with BADS 2 capsules twice daily. Treatment efficacy was evaluated using "Criteria for premature ejaculation" (CriPE) and IIEF-5 questionnaires at baseline and on completion of the treatment course. Besides, a polymorphism in the serotonin transporter gene (5-HTTLPR) was tested. RESULTS: The treatment was effective in 35 (74.5%) and 48 (82.7%) patients of group 1 and 2, respectively (p<0.0001) with similar statistically significant (p<0.001) improvement in erectile function. According to CriPE scores, 6.4, 8.5, 23.4, 10.6 and 12.8% patients of group 1 and 10.3, 1.7, 40.0, 25.9, 10.3 and 31.0% patients of group 2 with LaLa, LaLg, LgLg, Sla, SLg, SS genotypes were rendered free of SPE, respectively. CONCLUSION: Treating ED-associated SPE with the combination of serotonin precursors and tadalafil can better improve ejaculatory function recovery compared with PDE-5i monotherapy.

Milk Collected at Night Induces Sedative and Anxiolytic-Like Effects and Augments Pentobarbital-Induced Sleeping Behavior in Mice.

Milk has long been known and used to promote sleep. The sleep-promoting effect of milk has been attributed to its psychological associations (i.e., the memory of a mother giving milk at bedtime) and its rich store of sleep-promoting constituents (e.g., tryptophan). Studies have shown that milk harvested at night (Night milk) contains exceptionally high amounts of tryptophan and melatonin. In the present study, we evaluated the psychopharmacological properties of Night milk, particularly its probable sleep-promoting/enhancing, and anxiolytic effects. Night milk was orally administered to ICR mice at various concentrations (100, 200, or 300 mg/kg). An hour after administration, assessment of its sedative (open-field and rotarod tests) and sedative sleep-potentiating effects (pentobarbital-induced sleeping test) was conducted. For comparison, the effects of Day milk (daytime milking) were also assessed. In addition, the effects of Night milk on anxiety behavior (elevated plus maze [EPM] test) and electroencephalographic (EEG) waves were evaluated. Night milk-treated animals exhibited decreased spontaneous locomotion (open-field test) and impaired motor balance and coordination (rotarod test). Furthermore, Night milk shortened the sleep onset and prolonged the sleep duration induced by pentobarbital sodium. These effects were comparable to that of diazepam. In addition, Night milk significantly increased the percentage of time spent and entries into the open arms of the EPM, indicating that it also has anxiolytic effects. No significant changes in EEG waves were observed. Altogether, these findings suggest that Night milk is a promising natural aid for sleep- and anxiety-related disturbances.

Chronic treatment with a tryptophan-rich protein hydrolysate improves emotional processing, mental energy levels and reaction time in middle-aged women.

Common pharmacological treatments of mood disorders aim to modulate serotonergic neurotransmission and enhance serotonin levels in the brain. Brain serotonin levels are dependent on the availability of its food-derived precursor essential amino acid tryptophan (Trp). We tested the hypothesis that delivery of Trp via food may serve as an alternative treatment, and examined the effects of a Trp-rich, bioavailable dietary supplement from egg protein hydrolysate on cognitive and emotional functions, mood state, and sleep quality. In a randomised, placebo-controlled, parallel trial, fifty-nine mentally and physically healthy women aged 45-65 years received placebo (n 30) or the supplement (n 29) (both as 0.5 g twice per d) for 19 d. Emotional processing was significantly changed by supplementation, exhibiting a shift in bias away from negative stimuli. The results for the Affective Go/No-Go Task exhibited a slowing of responses to negative words, suggesting reduced attention to negative emotional stimuli. The results for the Facial Emotional Expression Rating Task also supported a shift away from attention to negative emotions and a bias towards happiness. An increase in arousal-like symptoms, labelled 'high energy', shorter reaction times and a slight benefit to sustained attention were observed in the treated subjects. Finally, when the supplement was taken 60-90 min before bedtime, a feeling of happiness before going to bed was consistently reported. In summary, daily consumption of a low-dose supplement containing bioavailable Trp may have beneficial effects on emotional and cognitive functions.