Water-soluble vitamin insufficiency, deficiency and supplementation in children and adolescents with a psychiatric disorder: a systematic review and meta-analysis

Nutrition is fundamental for brain development, but relatively little is known about water-soluble vitamin (WSV) levels and the effect of supplementation on psychiatry symptoms in children and adolescents (CAD) with psychiatric disorders. Our team systematically reviewed all studies concerning WSV abnormalities or supplementation in CAD with any psychiatric disorder. We searched for original studies published between 1990 and 15/05/2020 which were not based on retrospective chart review and which included WSV blood level measurements or investigated the effect of WSV supplementation on psychiatric symptoms in psychiatric patients aged 18 or under. Forty-two articles were included, 69% of which (N = 29) examined Autism Spectrum Disorders (ASD), with most of these assessing folate or vitamin B12 supplementation (N = 22, 75.9% of ASD studies). Meta-analyses showed significantly lower vitamin B12 levels in ASD and ADHD patients vs. healthy controls (HC), while folate levels were higher in ADHD patients vs. HC. Most of the studies (9/10, 90%) showed a decrease in symptoms as measured by clinical scales after supplementation. There was significant heterogeneity between the studies, however many found different types of vitamin abnormalities in CAD with psychiatric disorders

Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain.

Background: Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene mutation have been postulated as a possible cause of recurrent miscarriage (RM). There is a wide variation in the prevalence of MTHFR polymorphisms and homocysteine (Hcy) plasma levels among populations around the world. The present study was undertaken to investigate the possible association between hyperhomocysteinemia and its causative genetic or acquired factors and RM in Catalonia, a Mediterranean region in Spain. Methods: Sixty consecutive patients with ≥ 3 unexplained RM and 30 healthy control women having at least one child but no previous miscarriage were included. Plasma Hcy levels, MTHFR gene mutation, red blood cell (RBC) folate and vitamin B12 serum levels were measured in all subjects. Results: No significant differences were observed neither in plasma Hcy levels, RBC folate and vitamin B12 serum levels nor in the prevalence of homozygous and heterozygous MTHFR gene mutation between the two groups studied. Conclusions: In the present study RM is not associated with hyperhomocysteinemia, and/or the MTHFR gene mutation

High amino acid osmotrophic incorporation by marine eukaryotic phytoplankton revealed by click-chemistry

pages, 7 figures.-- Data Availability Statement: Raw sequences are publicly available at the European Nucleotide Archive (https://www.ebi.ac.uk/ena) under the accession number PRJEB63614. The datasets generated for this study are available on request to the corresponding authors.The osmotrophic uptake of dissolved organic compounds in the ocean is considered to be dominated by heterotrophic prokaryotes, whereas the role of planktonic eukaryotes is still unclear. We explored the capacity of natural eukaryotic plankton communities to incorporate the synthetic amino acid L-homopropargylglycine (HPG, analogue of methionine) using biorthogonal noncanonical amino acid tagging (BONCAT), and compared it with prokaryotic HPG use throughout a 9-day survey in the NW Mediterranean. BONCAT allows to fluorescently identify translationally active cells, but it has never been applied to natural eukaryotic communities. We found a large diversity of photosynthetic and heterotrophic eukaryotes incorporating HPG into proteins, with dinoflagellates and diatoms showing the highest percentages of BONCAT-labelled cells (49 ± 25% and 52 ± 15%, respectively). Among them, pennate diatoms exhibited higher HPG incorporation in the afternoon than in the morning, whereas small (≤5 μm) photosynthetic eukaryotes and heterotrophic nanoeukaryotes showed the opposite pattern. Centric diatoms (e.g., Chaetoceros, Thalassiosira, Lauderia spp.) dominated the eukaryotic HPG incorporation due to their high abundances and large sizes, accounting for up to 86% of the eukaryotic BONCAT signal, and strongly correlating with bulk 3H-leucine uptake rates. When including prokaryotes, eukaryotes were estimated to account for 19–31% of the bulk BONCAT signal. Our results evidence a large complexity in the osmotrophic uptake of HPG, which varies over time within and across eukaryotic groups, and highlights the potential of BONCAT to quantify osmotrophy and protein synthesis in complex eukaryotic communitiesThis work was funded by the Spanish Ministry of Science, Innovation and Universities (MICINN) through the MIAU (RTI2018-101025-30-B-I00) and MICOLOR (PID2021-125469NB-C31) projects and the Ramon y Cajal contract to C.R.G. (RYC2019-026758-I), with funding from the Spanish Government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S). C.M. was supported by the Juan de la Cierva-formación fellowship (FJC2021-047745-34 I), funded by the Spanish Ministry of Science and Innovation (MCIN/AEI) and the EU (“NextGenerationEU”/PRTR)Peer reviewe

Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: A randomized clinical trial

This article has been accepted for publication in Clinical Infectious Diseases ©2014 The Authors .Published by Oxford University Press on Clinical Infectious Disease 60.5. DOI: 10.1093/cid/ciu898Background. It is unclear whether metabolic or body composition effects may differ between protease inhibitor-based regimens recommended for initial treatment of HIV infection. Methods. ATADAR is a phase IV, open-label, multicenter randomized clinical trial. Stable antiretroviral-naive HIV-infected adults were randomly assigned to atazanavir/ritonavir 300/100 mg or darunavir/ritonavir 800/100 mg in combination with tenofovir/emtricitabine daily. Pre-defined end-points were treatment or virological failure, drug discontinuation due to adverse effects, and laboratory and body composition changes at 96 weeks. Results. At 96 weeks, 56 (62%) atazanavir/ritonavir and 62 (71%) darunavir/ritonavir patients remained free of treatment failure (estimated difference 8.2%; 95%CI -0.6 to 21.6); and 71 (79%) atazanavir/ritonavir and 75 (85%) darunavir/ritonavir patients remained free of virological failure (estimated difference 6.3%; 95%CI -0.5 to 17.6). Seven vs. five patients discontinued atazanavir/ritonavir or darunavir/ritonavir due to adverse effects. Total and HDL cholesterol similarly increased in both arms, but triglycerides increased more in atazanavir/ritonavir arm. At 96 weeks, body fat (estimated difference 2862.2 gr; 95%CI 726.7 to 4997.7; P=0.0090), limb fat (estimated difference 1403.3 gr; 95%CI 388.4 to 2418.2; P=0.0071), and subcutaneous abdominal adipose tissue (estimated difference 28.4 cm2; 95%CI 1.9 to 55.0; P=0.0362) increased more in atazanavir/ritonavir than in darunavir/ritonavir arm. Body fat changes in atazanavir/ritonavir arm were associated with higher insulin resistance. Conclusions. We found no major differences between atazanavir/ritonavir and darunavir/ritonavir in efficacy, clinically-relevant side effects, or plasma cholesterol fractions. However, atazanavir/ritonavir led to higher triglycerides and total and subcutaneous fat than darunavir/ritonavir and fat gains with atazanavir/ritonavir were associated with insulin resistanceThis is an Investigator Sponsored Research study. It was supported in part by research grants from Bristol‐Myers Squibb and Janssen‐Cilag; Instituto de Salud Carlos III (PI12/01217) and Red Temática Cooperativa de Investigación en SIDA G03/173 (RIS‐EST11), Ministerio de Ciencia e Innovación, Spain. (Registration number: NCT01274780; registry name: ATADAR; EUDRACT; 2010‐021002‐38)

Vitamin A and E content in early stages of cephalopods and their dietary effects in Octopus vulgaris paralarvae

6 pages, 1 figure, 3 tablesThe present study was designed to provide a look at the vitamin content of the early stages of cephalopods as an approach to their vitamin requirements in culture. Vitamin A and E profiles of the European cuttlefish Sepia officinalis, European squid Loligo vulgaris and common octopus Octopus vulgaris laboratory hatchlings and wild juveniles were analyzed. In addition, for O. vulgaris we determined vitamin A and E profiles of mature ovaries and eggs at different stages of development, and followed their possible dietary effects during the first month of paralarval rearing. We also analyzed vitamin A and E content of the live prey, i.e. Artemia nauplii, Maja brachydactyla hatchling crab zoeae and the mysidacean shrimp Leptomysis buergii. In the octopus ovaries and eggs, the vitamin A and E concentrations remained globally higher compared to paralarvae and wild juveniles. The vitamin A content in early stages of cephalopods was not much different from that observed in other marine molluscs and fish larvae and is expected to come from the carotenoid pool of their crustacean prey. Relatively high content of vitamin E was observed in the octopus ovaries, eggs, hatchlings and juveniles of the three cephalopod species analyzed. These levels are probably related to the high percentage of long chain polyunsaturated fatty acids (PUFA) that are particularly high in paralarval and juvenile cephalopods. The vitamin E content of the natural prey, M. brachydactyla and L. buergii, seemed to match or exceed the dietary needs of the three species of cephalopods analyzed. The vitamin E content of the Artemia-fed O. vulgaris increased during the rearing period and the content of the one month of age paralarvae did not differ from the content in wild octopus juveniles, suggesting that this prey may provide sufficient tocopherol for the young octopusesR. Villanueva was funded by the Xarxa de Referència de Recerca i Desenvolupament en Aqüicultura de la Generalitat de Catalunya; Planes Nacionales de Cultivos Marinos, JACUMAR, Secretaría General de Pesca Marítima, Ministerio de Pesca, Agricultura y Alimentación, Spain; and by the Concerted Action CEPHSTOCK from the Commission of the European CommunitiesPeer reviewe

Uric acid administration for neuroprotection in patients with acute brain ischemia

Uric acid is the end product of purine metabolism and a powerful water-soluble antioxidant and radical scavenger in humans whose generation is increased in situations of oxidative stress, such as brain ischemia. Although hyperuricemia has been related to an increased risk of cardiovascular events, the association was not found significant in many studies after adjustment for the effect of confounders. In the ischemic rat brain, the administration of uric acid results in neuroprotection and improved behavioral outcome. The severity of neurological impairment and the volume of infarction in patients with stroke have been found inversely related to the concentration of uric acid. In healthy volunteers, uric acid has been administered without untoward effects to show a conspicuous reduction of oxidative stress. We hypothesize that the administration of uric acid could be beneficial and cost effective in patients sustaining acute oxidative stress, such as those with acute ischemic stroke. Uric acid could also extend to more than 3 h the therapeutic window of rt-PA after stroke and it could limit the appearance of neurobehavioral changes after cardiopulmonary bypass. Prospective double blind randomized controlled trials are needed to test the value of uric acid in these clinical settings in which oxyradical formation is prominent. © 2003 Elsevier Ltd. All rights reserved.Peer Reviewe

Neutrophil Infiltration Increases Matrix Metalloproteinase-9 in the Ischemic Brain after Occlusion/Reperfusion of the Middle Cerebral Artery in Rats

Matrix metalloproteinase-9 (MMP-9) activity increases in the brain during the first day after focal ischemia and might be involved in the pathogenesis of tissue damage. We previously showed MMP-9 in the extracellular space of brain parenchyma along with neutrophil recruitment after ischemia. In the present study, we tested whether neutrophils were a direct source of enhanced MMP-9 in the ischemic brain. Neutrophil infiltration was prevented either by injecting an antibody against ICAM-1, which abrogates neutrophil adhesion to the endothelial vessel wall, or by inducing neutropenia. One-hour intraluminal middle cerebral artery occlusion with reperfusion was induced, and studies were performed at 24 hours. Circulating neutrophils expressed 95-kDa MMP-9 and dimers, and infiltrated neutrophils stained positive for MMP-9. The expression of MMP-9 (mainly 95-kDa proform and dimers and, to a lesser extent, 88-kDa form) increased in brain after ischemia/reperfusion. Treatments preventing neutrophil infiltration failed to preclude the ischemia-induced increase in 88-kDa MMP-9 form and gelatinase activity in neurons and blood vessels. However, these treatments prevented the major increase in 95-kDa MMP-9 form and dimers. We conclude that neutrophil infiltration highly contributes to enhanced MMP-9 in the ischemic brain by releasing MMP-9 proform, which might participate in the tissular inflammatory reaction.Supported by grants from the European Commission (CE QLG1-CT-2000-00562), Fondo de Investigaciones Sanitaras (FIS 01/0099), and Ministerio de Ciencia y Tecnologia (SAF2002-01963)Peer Reviewe

Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain.

Background: Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene mutation have been postulated as a possible cause of recurrent miscarriage (RM). There is a wide variation in the prevalence of MTHFR polymorphisms and homocysteine (Hcy) plasma levels among populations around the world. The present study was undertaken to investigate the possible association between hyperhomocysteinemia and its causative genetic or acquired factors and RM in Catalonia, a Mediterranean region in Spain. Methods: Sixty consecutive patients with ≥ 3 unexplained RM and 30 healthy control women having at least one child but no previous miscarriage were included. Plasma Hcy levels, MTHFR gene mutation, red blood cell (RBC) folate and vitamin B12 serum levels were measured in all subjects. Results: No significant differences were observed neither in plasma Hcy levels, RBC folate and vitamin B12 serum levels nor in the prevalence of homozygous and heterozygous MTHFR gene mutation between the two groups studied. Conclusions: In the present study RM is not associated with hyperhomocysteinemia, and/or the MTHFR gene mutation

Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.

BACKGROUND & AIMS: In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension. METHODS: Ex vivo: Hepatic stellate cells phenotype was analysed in human precision-cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. HSC phenotype, proliferation and viability were assessed in LX2, and in primary human and rat HSC treated with mitoquinone or vehicle. In vivo: CCl4 - and thioacetamide-cirrhotic rats were treated with mitoquinone (5 mg/kg/day) or the vehicle compound, DecylTPP, for 2 weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, HSC phenotype and liver inflammation. RESULTS: Mitoquinone deactivated human and rat HSC, decreased their proliferation but with no effects on viability. In CCl4 -cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved HSC phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide-cirrhotic model. CONCLUSION: We propose mitochondria-targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis