Search

Objective While greater body mass index (BMI) is associated with increased risk of developing atrial fibrillation (AF), the impact of BMI on outcomes in newly diagnosed AF is unclear. We examine the influence of BMI on outcomes and whether this is modified by sex and evaluate the effect of non-vitamin K oral anticoagulants (NOACs) in patients with high BMI.Methods GARFIELD-AF is a prospective registry of 52 057 newly diagnosed AF patients. The study population comprised 40 482 participants: 703 underweight (BMI

Manzamines are chemically related compounds extracted from the methanolic extract of Acanthostrongylophora ingens species. Seven compounds were identified by our research group and are being characterized. As their biological target is unknown, this work is based on previous screening work performed by Mayer et al., who revealed that manzamine A could be an inhibitor of RSK1 kinase. Within this work, the RSK1 N-terminal kinase domain is exploited as a target for our work and the seven compounds are docked using Autodock Vina software. The results show that one of the most active compounds, Manzamine A N-oxide (5), with an IC50 = 3.1 μM, displayed the highest docking score. In addition, the compounds with docking scores lower than the co-crystalized ligand AMP-PCP (−7.5 and −8.0 kcal/mol) for ircinial E (1) and nakadomarin A (7) were found to be inferior in activity in the biological assay. The docking results successfully managed to predict the activities of four compounds, and their in silico results were in concordance with their biological data. The β-carboline ring showed noticeable receptor binding, which could explain its reported biological activities, while the lipophilic side of the compound was found to fit well inside the hydrophobic active site.

Tetrahydrobiopterin (BH4) and 4-amino-tetrahydrobiopterin (ABH4) prevent acute rejection after solid organ transplantation. Moreover, BH4 also attenuates ischemia-reperfusion injury (IRI). The mechanisms underlying these protective effects are poorly defined. Activation of intracellular signaling proteins, including the mitogen-activated protein kinases (MAPKs) ERK, p38, and JNK, and the excessive production of mitochondrial reactive oxygen species (ROS) are observed mainly during early reperfusion. While the role of ROS in the initiation and progression of IRI is well understood, the contribution of individual signaling pathways is less clear. Here, we tested the potential effects of BH4 and ABH4 on MAPK activity and mitochondrial ROS levels. During hypoxia and reoxygenation (H/R), all three MAPKs were activated during early reoxygenation in cardiomyocytes and endothelial cells. p38 and JNK activation were further augmented by BH4 and ABH4, whereas ERK activation was not affected. Pretreatment with BH4 and ABH4 reduced the basal mitochondrial ROS levels as well as the H/R-induced increase in ROS. Prolonged incubation with ABH4, however, showed pro-apoptotic effects in cardiomyocytes. These data suggest that a protective effect of BH4 and ABH4 pretreatment may be attributed mainly to their antioxidant capacity. The effects on intracellular signaling are complex and warrant further investigations.

Alkylglycerol monooxygenase (AGMO; EC 1.14.16.5) is the only enzyme known to cleave the O-alkyl ether bond of alkylglycerols in humans. It is an integral membrane protein with nine predicted transmembrane domains. We attempted to express and purify full-length and truncated forms of AGMO in Escherichia coli. Full-length AGMO could not be expressed in three different E. coli expression strains, three different expression vectors and several induction systems. We succeeded, however, in expression of three N-terminally strep-tagged truncated forms, named active sites 1, 2 and 3, with 205, 134 and 61 amino acids, respectively. Active site 1 fragment, containing two predicted transmembrane regions, a membrane associated region and all known amino acid residues important for catalytic activity, was not fully soluble even in 8 M urea. Active site 2 containing only one predicted membrane associated domain required 8 M urea for solubilisation and eluted in gel filtration in 1 M urea as a trimer. Active site 3 with no hydrophobic domain eluted in gel filtration in 1 M urea as monomer and dimer. These results show that even truncated forms of AGMO are barely soluble when expressed in E. coli and show a high tendency for aggregation.

Alkylglycerol monooxygenase is a tetrahydrobiopterin-dependent enzyme that cleaves the O-alkyl-bond of alkylglycerols. It is an exceptionally unstable, hydrophobic membrane protein which has never been purified in active form. Recently, we were able to identify the sequence of alkylglycerol monooxygenase. TMEM195, the gene coding for alkylglycerol monooxygenase, belongs to the fatty acid hydroxylases, a family of integral membrane enzymes which have an 8-histidine motif crucial for catalysis. Mutation of each of these residues resulted in a complete loss of activity. We now extended the mutational analysis to another 25 residues and identified three further residues conserved throughout all members of the fatty acid hydroxylases which are essential for alkylglycerol monooxygenase activity. Furthermore, mutation of a specific glutamate resulted in an 18-fold decreased affinity of the protein to tetrahydrobiopterin, strongly indicating a potential important role in cofactor interaction. A glutamate residue in a comparable amino acid surrounding had already been shown to be responsible for tetrahydrobiopterin binding in the aromatic amino acid hydroxylases. Ab initio modelling of the enzyme yielded a structural model for the central part of alkylglycerol monooxygenase where all essential residues identified by mutational analysis are in close spatial vicinity, thereby defining the potential catalytic site of this enzyme.

Tetrahydrobiopterin (BH4) is a major endogenous vasoprotective agent that improves endothelial function by increasing nitric oxide (NO) synthesis and scavenging of superoxide and peroxynitrite. Accordingly, administration of BH4 is considered as a promising therapy of cardiovascular diseases associated with endothelial dysfunction and oxidative stress. In a recent study we identified a novel function of BH4 that might contribute to the beneficial vascular effects of the pteridine. As demonstrated with cultured porcine aortic endothelial cells, oxidative inactivation of soluble guanylate cyclase with nitroglycerin or the heme-site inhibitor ODQ (1H-[1,2,4]-oxadiazolo[4,3-a]quinoxaline-1-one) resulted in a decrease in NO-induced cGMP accumulation that was insensitive to scavengers of reactive oxygen species but prevented upon supplementation of the cells with BH4. Tetrahydroneopterin had the same effect and virtually identical results were obtained with RFL-6 fibroblasts, suggesting that our observation reflects a general feature of tetrahydropteridines that is unrelated to NO synthase function and not limited to endothelial cells. Protection of soluble guanylate cyclase against oxidative inactivation may contribute to the known beneficial effects of BH4 in cardiovascular disorders associated with oxidative stress.

Current knowledge distinguishes three classes of tetrahydrobiopterin-dependent enzymes as based on protein sequence similarity. These three protein sequence clusters hydroxylate three types of substrate atoms and use three different forms of iron for catalysis. The first class to be discovered was the aromatic amino acid hydroxylases, which, in mammals, include phenylalanine hydroxylase, tyrosine hydroxylase, and two isoforms of tryptophan hydroxylases. The protein sequences of these tetrahydrobiopterin-dependent aromatic amino acid hydroxylases are significantly similar, and all mammalian aromatic amino acid hydroxylases require a non-heme-bound iron atom in the active site of the enzyme for catalysis. The second classes of tetrahydrobiopterin-dependent enzymes to be characterized were the nitric oxide synthases, which in mammals occur as three isoforms. Nitric oxide synthase protein sequences form a separate cluster of homologous sequences with no similarity to aromatic amino acid hydroxylase protein sequences. In contrast to aromatic amino acid hydroxylases, nitric oxide synthases require a heme-bound iron for catalysis. The alkylglycerol monooxygenase protein sequence was the most recent to be characterized. This sequence shares no similarity with aromatic amino acid hydroxylases and nitric oxide synthases. Motifs contained in the alkylglycerol monooxygenase protein sequence suggest that this enzyme may use a di-iron center for catalysis.

Ischemia-reperfusion injury is a primarily non-allospecific event leading to the depletion of the essential nitric oxide synthase cofactor and potent antioxidant tetrahydrobiopterin. Suboptimal concentrations of tetrahydrobiopterin result in a reduced biosynthesis of nitric oxide leading to vascular endothelial dysfunction. Tetrahydrobiopterin supplementation has been shown to protect from this pathological state in a plethora of cardiovascular diseases including transplant-related ischemia-reperfusion injury. Even though still controversially discussed, there is increasing evidence emerging from both human as well as animal studies that tetrahydrobiopterin-mediated actions rely on its nitric oxide synthase cofactor activity rather than on its antioxidative properties. Herein, we review the current literature regarding the role of tetrahydrobiopterin in ischemia-reperfusion injury including our experience acquired in a murine pancreas transplantation model.

The tetrahydrobiopterin-dependent degradation of ether lipids by alkylglycerol monooxygenase (AGMO) produces fatty aldehydes, which are toxic to cells. Therefore, it is of great physiological importance that these harmful compounds are converted into their corresponding, less toxic fatty acids by fatty aldehyde dehydrogenase (FALDH). Dysfunction of this enzyme causes Sjögren-Larsson syndrome. This severe inherited disorder is accompanied by symptoms such as ichthyosis, mental retardation and spasticity. Surprisingly, fatty alcohols and not fatty aldehydes were found to accumulate in fibroblasts of Sjögren-Larsson syndrome patients, suggesting that there can be wide-ranging alterations in the lipid composition of patient cells. In particular, this has to be considered when searching for possible treatment options for patients suffering from Sjögren-Larsson syndrome. For example, inhibition of fatty aldehyde producing ether lipid degradation would have multiple implications on ether lipid- and fatty alcohol-mediated signalling pathways.

Sand and dust storms (SDS) are an important threat to life, health, property, environment and economy in many countries, and play a significant role in different aspects of weather, climate and atmospheric chemistry. There is an increasing need for SDS accurate information and predictions to support early warning systems, and preparedness and mitigation plans. The present contribution introduces the current activities of the Regional Center for Northern Africa, Middle East and Europe of the WMO Sand and Dust Storm Warning Advisory and Assessment System (SDS-WAS). The Center has the mission is to enhance the ability of countries in the region to deliver timely and quality SDS forecasts, observations, information and knowledge to users through an international partnership of research and operational communities.

Com o fim de minimizar os custos de produç o, os pequenos produtores da bacia leiteira de Pelotas uilizam como adubaç o máxima para a produç o de silagem, aquela recomendada para produç o de gr os. Por isso o estudo averiguou o efeito de dois níveis de adubaç o (gr os; silagem) sobre a qualidade, o teor e a suficiência de nutrientes para três categorias animais (lactaç o; crescimento e terminaç o em bovinos) nas silagens de duas culivares de milho (variedade; híbrido). Foram esimados os teores dos parâmetros de qualidade (matéria seca, matéria mineral, matéria orgânica, proteína bruta, fibra bruta, extrato n o nitrogenado, fibra em detergente neutro, fibra em detergente ácido, lignina e digesibilidade in vitro da matéria orgânica) e os nutrientes disponíveis (proteína bruta diges vel, nutrientes diges veis totais, energia metabolizável, energia líquida lactaç o, energia líquida mantença, energia líquida ganho, cálcio e fósforo) por kg de matéria seca. Foi esimada a capacidade de produç o de leite por tonelada e por hectare. O desenho experimental foi o de blocos completos casualizados, com quatro repeiç es. Os teores de nutrientes das silagens das duas culivares, nos dois níveis de adubaç o, s o caracterísicos daqueles encontrados em silagens de milho. A adubaç o para produç o de silagem aumenta os teores da matéria mineral, da proteína bruta e da proteína bruta diges vel, bem como o coeficiente de digesibilidade in vitro da matéria orgânica. As silagens das duas culivares apresentam energia suficiente para produç o de leite e carne, entretanto s o muito deficientes em termos proteína, cálcio e fósforo, nos dois níveis de adubaç o. A adubaç o para produç o de silagem apresenta maior potencial de produç o de leite por tonelada e por hectare, nas duas culivares. recomendável a uilizaç o do nível de adubaç o para produç o de silagem, bem como a administraç o de suplemento protéico e de minerais aos animais.

Este estudo averiguou o efeito de dois níveis de adubaç o [gr osrNAG (N 80 kg; P2O5 50 kg; K2O 70 kg); silagemrNAS ( N 160 kg; P2O5 130 kg; K2O 220 kg)] sobre: as produç es de matéria fresca (PMF) e matéria seca (PMS), e as disponibilidades de matéria seca diges vel (DMSD), nutrientes diges veis totais (DNDT), proteína bruta (DPB) e proteína bruta diges vel (DPBD) por hectare, de duas culivares de milho (variedaderMV; híbridorMH) semeadas em parcelas consituídas de 6 linhas de 7 m de comprimento. Após a colheita, o material foi homogeneizado e acondicionado em baldes plásicos (18 x 17 cm). Determinourse também a composiç o percentual das partes da planta e o custo operacional total (COT) de produç o das silagens. O desenho experimental foi ao acaso em arranjo fatorial 2x2, com quatro repeiç es. Foram detectadas diferenças significantes para a PMF entre culivares e entre níveis de adubaç o por culivar e para DPB e DPBD entre níveis de adubaç o. O MH demonstrou melhor desempenho que o MV em todos os parâmetros de produividade, nos dois níveis de adubaç o. O NAS propiciou um aumento das produç es de todos os parâmetros de produividade por hectare nas duas culivares, bem como um aumento da paricipaç o do colmo e um decréscimo da paricipaç o da espiga sem palha em relaç o à planta inteira. No NAG o COT dos parâmetros de produividade foi semelhante nas duas culivares; no NAS o COT de PMS, DMSD e DNDT e, principalmente, de DPB e DPBD foi maior no MV.

ABSTRACTStaphylococcus aureus is the leading etiologic agent of orthopedic implant infections. Here a ribocluster of 27 S. aureus strains underwent further molecular characterization and subtyping by multilocus sequence typing (MLST) and spa-typing. This cluster had been detected by automated ribotyping (with EcoRI as restriction enzyme) of 200 S. aureus isolates from periprosthetic infections come for revision at the Rizzoli Orthopaedic Institute. The ribocluster, consisting of agr type III isolates, with a 74% co-presence of bone sialoprotein-binding (bbp) and collagen-binding (cna) genes, turned out devoid of mecA and IS256 and exhibited a high prevalence of toxic shock syndrome toxin gene (tst, 85%). Sequences achieved by spa typing and MLST were analyzed by BURP and goeBURST. Two predominant spa types, t012 (32%) and t021 (36%), and one predominant sequence type, ST30 (18/27, 67%), a Staphylococcus aureus lineage spread worldwide and regarded as the ancestor of MLST CC30, were identified. Two new sequence types (ST2954, ST2960) and one new spa type (t13129) were detected for the first time. BURP clustered the isolates into two spa clonal complexes, CC021/012 (22/27, 81%) and CC166 (4/27, 15%), plus one singleton, while goeBURST recognized solely MLST CC30. Interestingly, the 27-strains cluster detected by ribotyping corresponded exactly to CC30.

We investigated a possible involvement of nitric oxide formed by inducible nitric oxide synthase (iNOS) in the signaling cascade leading to growth inhibition and differentiation in the human neuroblastoma cell line SK-NSII. Treatment of SK-N-SH with interferon-γ (IFN-γ) plus interleukin-lß (IL-lß) led to induction of iNOS, growth inhibition and an altered cell shape. However two inhibitors of iNOS were not able to prevent cytokine induced changes. In addition, IFN-γ alone led to growth inhibition in absence of iNOS induction. Inhibition of the induced indoleamine 2,3-dioxygenase (IDO) activity also did not prevent growth inhibition. Our findings show that mechanisms other than NO and IDO can control interferon-y-induced growth inhibition of SK-N-SH cells.

Increased neopterin concentrations in serum and urine indicate activation of cell-mediated immunity. In this study, urinary neopterin concentrations of a family consisting of 1 child (aged 5 years), her parents, and her grandparents were determined over a one year period and the course of neopterin levels was compared. Urine specimens were taken every second week during 1 year beginning in June. All 5 individuals lived in the same house, child and her parents separated by one floor from the grandparents. Neopterin concentrations were determined by high Performance liquid chromatography. In adults, neopterin concentrations were very stable throughout the year and peak increases occurred only rarely. In contrast, 5 sharp peaks of urinary neopterin concentrations were observed in the child, all occurring during the period when she was attending the kindergarten. Comparing the course of neopterin concentrations between the persons tested, several corresponding elevations of urinary neopterin were detected in the child and her relatives. The best association was detected between the child and her father (3 peaks of neopterin concentrations were observed, 1 of which coinciding with a peak in the child and two peaks with two weeks delay in the father). Between the child and her mother 1 corresponding neopterin peak was observed. One highly increased urinary neopterin concentration was observed in the grandmother which corresponded to a peak in the child with two weeks delay, a similar Observation was made between the child and her grandfather. In summary, high degree of correspondence in neopterin peaks was detected between child and adults. The data render it likely that the child was transmitting infectious diseases which she acquired at the kindergarten to her relatives, and the data are in line with the assumption that a dose family contact between individuals increases the risk of infectious disease transmission via household contact.

Este estudo visou avaliar o efeito da amonização do feno de capim-Annoni 2 (Eragrostis plana Nees) com 4% de uréia, em base de matéria seca, sobre os teores de proteína bruta (PB), fibra detergente neutro (FDN), fibra detergente ácido (FDA), hemicelulose (HEM), celulose (CEL) e lignina (LIG) e o coeficiente da digestibilidade in vitro da matéria orgânica (DIVMO), em cinco épocas de corte (30, 60, 90, 120, 150 dias). O delineamento experimental foi o de blocos completos casualisados, em número de quatro, num arranjo fatorial (2x5) com dois fatores: tratamento dos fenos (2) e épocas de corte (5). A comparação entre os dois grupos de fenos (amonizados ou não) demonstrou que a amonização propiciou aumento altamente significativo dos teores de PB. Por outro lado, a fração de FDA decresceu significantemente, juntamente com os teores de CEL, em função do tratamento com uréia. Não foram detectadas diferenças entre os tratamentos, relativamente aos teores de FDN, HEM, LIG e ao coeficiente da DIVMO. Inferiu-se que: 1. a amonização do feno de capim-Annoni 2 não afetou os teores de FDN , HEM, LIG e os coeficientes da DIVMO; 2. tratamento do feno de capim-Annoni 2 com uréia propiciou aumento nos teores de PB e decréscimo nos teores de FDA e CEL; 3. o capim-Annoni 2 pode ser fenado até os 90 dias de crescimento, sem que ocorram modificações expressivas dos parâmetros de qualidade, desde que o feno seja amonizado.

Within the European project MUNDUS, an assistive framework was developed for the support of arm and hand functions during daily life activities in severely impaired people. Potential users of this system are patients with high-level spinal cord injury and neurodegenerative neuromuscular diseases, such as amyotrophic lateral sclerosis, Friedreich ataxia, and multiple sclerosis. This contribution aims at designing a feedback control system for Neuro-Muscular Electrical Stimulation (NMES) to enable reaching functions in people with no residual voluntary control of the arm due to upper motor neuron lesions after spinal cord injury. NMES is applied to the deltoids and the biceps muscles and integrated with a three degrees of freedom (DoFs) passive exoskeleton, which partially compensates gravitational forces and allows to lock each DOF. The user is able to choose the target hand position and to trigger actions using an eyetracker system. The target position is selected by using the eyetracker and determined by a marker-based tracking system using Microsoft Kinect. A central controller, i.e. a finite state machine, issues a sequence of basic movement commands to the real-time arm controller. The NMES control algorithm sequentially controls each joint angle while locking the other DoFs. Daily activities, such as drinking, brushing hair, pushing an alarm button, etc., can be supported by the system. The robust and easily tunable control approach was evaluated with five healthy subjects during a drinking task. Subjects were asked to remain passive and to allow NMES to induce the movements. In all of them, the controller was able to perform the task, and a mean hand positioning error of less than five centimeters was achieved. The average total time duration for moving the hand from a rest position to a drinking cup, for moving the cup to the mouth and back, and for finally returning the arm to the rest position was 71 seconds.

The rabbit pyrogen assay identifies pyrogenic contaminations in drugs i.l1tend~d for parenteral use. In order to replace this test because of ethical and economical reasons, various in vitro methods have been developed in recent years. Here, we summarize our results on optimizing a test based on using interferony- treated monocytoid cell lines from man (THP-l) and mouse (RAW264.7). The read-out of the test is neopterin or nitrite, respectively, which is released into the supernatant in response to bacterial compounds. These are costimuli of the enzymes involved in neopterin and nitrite formation, i.e. GTP cyclohydrolase I and inducible nitric oxide synthase. The test reproducibly detects cell wall components from Gram-negative as well as from Gram-positive bacteria and mycobacteria. Furthermore, DNA and cell-free supernatants containing a number of bioactive but not further characterized proteins, both from Staphylococcus aureus, can be detected. Thus, this test is superior over the only in vitro alternative accepted in certain cases, namely the limulus amebocyte lysate assay. Results obtained by measuring neopterin or nitrite correlate well with formation of the endogenous pyrogen tumor necrosis factor-a, a read-out used by some other cell-based in vitro alternatives to the rabbit pyrogen test. We therefore think that the assay presented here has the potential to reduce or even replace the animal test.

Recently; the 4-amino analogue of tetrahydrobiopterin was found to be a strong inhibitor of nitric oxide synthase while being bound to the enzyme in a manner similar to the natural cofactor tetrahydrobiopterin. We were interested in the electronic properties of these and similar compounds and studied therefore the following model tetrahydropteridine structures: tetrahydrolumazine, tetrahydropterin, 4-amino-analogue of tetrahydropterin and N5-methyl-tetrahydropterin. Ab initio quantum chemical computations used the Hartree- Fode method with basis set 6-31G** after geometry optimization with basis set 3-21G*. Results reveal dramatic differences in distribution of electronic charge and all the molecular properties derived thereof~ between a) the lumazine system, b) the normal pterin system, and c) the 4-amino analogue. In contrast, differences of electronic properties between tetrahydropterin and its N5-methyl-derivative are negligible. Our results are compatible with recent speculations that the striking differences between the effects of the tetrahydropterin struculrc and its 4-amino analogue on cnznllatic activity may be due to electronic interaction between the pyrimidine moiety of the ptcrin ring systcm and the heme group.

O estudo comparou a produção de carne entre 13 cordeiros castrados aos 45 dias e 13 não castrados, procedentes do cruzamento de ovelhas Corriedale com Hampshire Down, nascidos em agosto de 1996 e abatidos aos 5 meses de idade, criados em condições extensivas de pastagem natural, na localidade de Aceguá, município de Bagé-RS. Foram coletados dados de produção de carne, morfologia in vivo e, na carcaça, componentes do peso vivo, composição regional e tecidual. Não se verificou diferença significativa entre cordeiros castrados e não castrados, concluindo-se que não há vantagem, quanto à produção de carne, em castrar os cordeiros muito jovens.This study has compared meat production among two groups of crossbred lambs Hampshire Down x Corriedale: 13 castrated at 45 days of age and 13 non-castrated (all born in August 1996 and slaughtered when five months old). The flock was raised on natural pasture, under an extensive grazing system, in Aceguá, Bagé, State of Rio Grande do Sul, Brazil. The characteristics research were meat production, morfology "in vivo" and carcass, living weight components, regional and tissue composition .There is no significant difference between castrate lambs and not castrate lambs. The results showed that there is not advantage in to castrate very young lambs, when the purpose is meat production

Foram utilizadas 16 carcaças de novilhos Holandês, criados em confinamento, dos 6 aos 24 meses de idade, com o objetivo de testar medidas realizadas na carcaça como estimadores do peso dos cortes do serrote. Utilizaram-se equações de regressão linear simples. As variáveis independentes foram: conformação, comprimento da carcaça e comprimento da perna e as dependentes foram: o peso dos cortes do serrote. Os resultados obtidos mostraram que a conformação, estimou com precisão o peso do tatu. O comprimento de carcaça mostrou ser bom estimador do patinho, do contrafilé e do tatu. O comprimento de perna, foi responsável apenas pela estimativa do peso da picanha. Os resultados permitem concluir que a conformação, o comprimento da carcaça e da perna, isoladamente, não devem ser utilizados para estimar o peso dos cortes do serrote.Sixteen carcasses of Holstein steers raised in feed lot from six to twenty four months, where used to test measurements of the carcass, trought simple linear regression equation, as predictors of hinquarter cuts weight. The independent variables were conformation, carcass length, leg length while the dependent variables were weight of hindquarter cuts. From the results obtained, one may conclude that conformation was a good predictor only for eye round; the carcass length was a good predictor for knuckie, stripling and eye round; leg length only estimated rump cover weight.

O estudo foi realizado com o objetivo de verificar a utilização do peso vivo (PV) como estimador do peso da carcaça quente (PCQ), dos cortes dianteiro (PD), costilhar (PC) e serrote (PS), assim como, quantificar a relação do PV com o PCQ e principais cortes da carcaça (PD, PC e PS). Foram utilizados 58 novilhos Hereford, criados em campo nativo e abatidos com 36 meses de idade. As equações de regressão obtidas foram: PCQ=-3,97+0,474(PV); PS=4,32+0,050(PV); PC=-5,26+0,092(PV) e PD=-0,54+0.043(PV), todas altamente significativas (PFifty eight Hereford steers, raised under native pasture conditions, slaughtered with an average age of thirty months, were used to study the feasibility of the use of live wheight (PV) as an estimator of the hot carcass weight (PCQ) and of cuts such as fore quarter (PD), ribs (PC) and hind pistol (PS), as well as to quantify the relationship of live weight with hot carcass weight and the main carcass cuts (PD, PC and PS). The regression equations obtained were: PCQ =-3.7 + 0.474 (PV); PS = 4.32 + 0.50 (PV); PC = -5.6 + 0.92 (PV) and PD =-0.4 + 0.43 (PV), all of them highly significant (P

Using a recently developed model of bacterially induced sepsis in baboons, we studied the time courses of pteridine and nitrate levels in plasma with regard to the dose of Escherichia coli. Eight animals were given a 2 h infusion of 2X 10" Colony Forming Units live E. coli/kg BW (group LOW), and six others 2X 10" CFU/kg BW (group HIGH). Endotoxin levels and, consequently, the TNF-a, IL-8, and IL-6 concentrations clearly corresponded with the infused amount of live E. coli. The neopterin/creatinine ratio increased in both groups up to 24 h, but was more pronounced in the HIGH group. In contrast, the biopterin/creatinine ratio increased in the HIGH group, but remained unchanged in the LOW group. Plasma nitrate levels remained at baseline (::::: 20 Ilmol!l) up to 4 h, but then increased three- to fourfold within the next 4 h and remained elevated in the HIGH group. In group LOW, the concentrations were unchanged throughout the observation period.

We have evaluated a new commercially available enzyme-linked immunorsorbant assay for neopterin :or its suitability in the context of screening of voluntary blood donors. The assay was performed on 1040 consecutive blood donors, and compared with radioimmunoassay and. in a fraction of 142 donors . . : Iso with high performance liquid chromatography. On repetitive assays of all donations showing a concentration exceeding 8.0 nmol/L in the initial assay. three of the radioimmunoassay results were identified as gross outliers. No such gross outliers were detected for the enzyme-linked immunosorbant assay. RegarJing the reproducibility of results exceeding a cut-off limit of \0 nmol/L neopterin. the enzyme-linked ;mmunosorbant assay was better than the radioimmunoassay. Moreover. the enzyme-linked immunosorbant assay was slightly superior to radioimmunoassay when both tests were compared with high performance liquid chromatography (based on linear regression analysis. evaluation of frequencies of concentrations bant assay was slightly superior to radioimmunoassay when both tests were compared with high performance liquid chromatography (based on linear regression analysis. evaluation of frequencies of concentrations rations. Its slight superiority compared to the conventional radioimmunoassay likely results from the higher degree of automatization employed.

Eleven mothers of 12 infants with human immunodeficiency virus type 1 (HIV-1) infection (all intravenous drug users) were followed throughout their pregnancies for evidence of clinical and immunological abnormalities. Intrauterine death occurred in one, growth retardation in 7/12 pregnancies. Moderate progression of HIV-l infection according to the Walter Reed Staging Classification was observed in 5/ 11 women during pregnancy. Two of them developed AIDS during follow up after delivery. Mean neopterin levels in the first, second and third trimester were significantly higher as compared to HIV-l seronegative pregnant women. Furthermore, concentrations of urinary neopterin increased significantly with the time of pregnancy in all HIV-1 seropositive women. Since higher urinary neopterin concentrations are predictive for more rapid disease progression in HIV infected patients the data may indicate that pregnancy increases the risk for developing AIDS. However, a possible influence of continuous drug use has to be considered.

Elevated production and excretion of neopterin indicate activation of cell-mediated immunity, since neopterin is produced in large quantities by human macrophages after stimulation with interferon gamma. In 21 patients, aged 9 to 19 years, with Crohn’s disease, urinary neopterin was measured on a total of 135 consecutive followup visits. Additionally, a large panel of anamnestic, clinical and laboratory data were obtained at every visit. Both the first visit data set (21 records) and the complete data set (135 records) were analyzed separately. As was previously demonstrated in adults with Crohn’s disease, neopterin excretion proved to be strongly correlated with overall rating of disease activity, and also with separate anamnestic, clinical and laboratory activity scores. Multiple regression analysis demonstrated that neopterin provides statistically independent information. Thus, measurement of neopterin concentrations as a marker for activation of cellular immune phenomena could aid in the monitoring of pediatric and juvenile Crohn’s disease.

Urine concentrations of neopterin, a marker for the activation of cellular immunity, were determined concomitantly with a large panel of hematological and immunological variables on 24 women with gynaecological cancers (12 uterine cervix, 5 endometrium, 7 ovary). There were 14 women investigated at first diagnosis of carcinoma, and 10 women were studied during follow-up (evidence of disease, only palliative treatment during the preceding three months). A statistically significant correlation was found between neopterin concentrations and number of circulating non-B lymphocytes expressing HLA-DR antigen. Neopterin concentrations, numbers of HLA-DR positive cells, and numbers of circulating leukocytes were significantly higher in women studied during follow-up, when compared with women freshly diagnosed. In contrast. numbers of CD4 +, CD3 +, CD19 + lymphocytes and of total lymphocytes in peripheral blood were significantly lower in women studied during follow-up. The results suggest that high neopterin levels in tumor patients indicate activation of early steps of cellular immune mechanisms.

To compare the involvement of cellular immunity in response to vaccination we have investigated urinary neopterin levels in daily follow-ups of children after vaccination with live measles/mumps vaccine and of adults after boosting with the soluble antigen tetanus toxoid. Neopterin levels distinctly peaked 8 - 11 days after vaccination with measles/mumps vaccine. In contrast, after boosting with soluble antigen tetanus toxoid neopterin levels remained unaffected. Large amounts of neopterin are produced by human monocytes/ macro phages on stimulation with gamma interferon. In patients neopterin concentrations reflect activation of cell mediated immunity. The data imply that distinct pathways of T cell activation are triggered in humans after immunization with live vaccine and with soluble antigen .

Abstract Background Non-specific low back pain (LBP) is usually self-limiting within 4-6 weeks. Longstanding pain and disability are not predictable from clinical signs or pathoanatomical findings. Pain cognition and physical performance have been shown to improve patients with chronic LBP following neurophysiological education. The primary aim of this study is to evaluate whether a specific cognitive based education programme for patients with LBP in primary care is more effective than normal care in terms of increased function. The secondary aims of the study are to evaluate whether this intervention also results in earlier return to work, decreased pain, increased patient satisfaction, increased quality-of-life, and cost utility. Methods/Design Cluster randomised controlled trial with 20 general practitioners and 20 physiotherapists in primary care as the unit of randomisation. Each practitioner will recruit up to 10 patients, aged 20 to 55 years, with non-specific sub-acute/chronic LBP of more than four weeks but less than 1 year's duration. Practitioners in the intervention arm will provide cognitive patient education intervention in up to four weekly sessions, each lasting 30 minutes. Practitioners in the control arm will provide normal treatment, but have to make four appointments for the patients. Patients, outcome assessors, and study statistician will be blinded to group allocation. Discussion We present the rationale and design of an ongoing RCT study that potentially offers an easily implemented treatment strategy for LBP patients in primary care. The results will be available in 2012. Trial registration ISRCTN04323845

Concentrations of interferon gamma in serum and of neopterin in serum and urine were determined in 55 Tanzanians attending a local hospital for various diseases or complaints. For comparison, serum concentrations of interferon gamma and of neopterin were also measured in 76 clinically healthy Austrian blood donors. Both interferon gamma and neopterin concentrations were significantly higher in patients than in blood donors. Both analytes were significantly correlated with each other, and both exhibited similar behaviour in dependence on clinical diagnosis. The results support use of neopterin determination for indirect measurement of endogenous production of interferon gamma.

A brief review is given on the value of neopterin determination as a biochemical marker for the in vivo activation state of cell-mediated immunity. In a broad spectrum of diseases which are recognized or supposed to involve activation of monocytes/macrophages by interferon gamma derived from activated T lymphocytes, the applicability and utility of this technically simple test for a variety of specific clinical questions have been demonstrated by a multitude of authors. Applications are e. g. early detection of immunological complications in recipients of allografts, monitoring of inflammatory flare-up in patients with autoimmune disorders, the management of patients with malignant tumours and the monitoring of the clinical course in individuals with various infections and particularly with the human immunodeficiency virus. By measuring levels of neopterin in body fluids, information on the actual state of cell~mediated immunity in vivo is obtained that is not easily achieved by other techniques.

In 1981 /82 we have reported that urinary neopterin concentrations were increased with high frequency in patients with haematological neoplasias. Seven years after this first report we have investigated whether the magnitude of the measured neopterin increase was associated with the subsequent survival of these patients. Complete clinical follow up data were available of 85 out of 115 patients initially investigated in this study. Overall, Kaplan-Meier analyses show that patients with Hodgkin's disease had the best prognosis compared to patients with non-Hodgkin's lymphoma and chronic myelogenous leukaemia. Hodgkin's patients had, on average, also lower urinary neopterin levels than the other patients. Higher neopterin concentrations were associated with worse prognosis in patients with Hodgkin's disease (p = 0.04, Breslow test) and with nonHodgkin's lymphoma (p = 0.035). In patients with chronic myelogenous leukaemia survival probability was lower in patients with higher neopterin concentrations 2 years after neopterin measurement (p < 0.01). Later on, no difference of survival was observed. Markedly decreasing survival was seen after an observation period longer than 4 years in both groups. Multivariate analyses show that the predictive value of neopterin concentrations was independent from stage of disease. We conclude that neopterin concentrations are of predictive relevance in patients with haematologic neopiasias.

Tetrahydrobiopterin (BH4) is an essential cofactor for the nitric oxide (NO) synthases and represents a critical determinant of NO production. BH4 depletion during ischemia leads to the uncoupling of the synthases, thus contributing to reperfusion injury due to increased superoxide formation. To examine whether BH4 supplementation attenuates ischemia-reperfusion injury, we clamped the left renal arteries of male Lewis rats immediately following right-side nephrectomy. BH4 tissue levels significantly decreased after 45 min of warm ischemia compared with levels in non-ischemic controls. Histopathology demonstrated significant tubular damage and increased peroxynitrite formation. Intravital fluorescent microscopy found perfusion deficits in the microvasculature and leakage of the capillary mesh. Supplemental BH4 treatment before ischemia significantly reduced ischemia-induced renal dysfunction, and decreased tubular histologic injury scores and peroxynitrite generation. BH4 also significantly improved microcirculatory parameters such as functional capillary density and diameter. These protective effects of BH4 on microvasculature were significantly correlated with its ability to abolish peroxynitrite formation. We suggest that BH4 significantly protects against acute renal failure following ischemia reperfusion. Whether BH4 has a therapeutic potential will require more direct testing in humans. [ABSTRACT FROM AUTHOR]

Animal flesh foods are rich in bioavailable iron but infrequently consumed by young children. We aimed to determine whether flesh food intake was associated with iron and anaemia status among 585 Malawian infants enroled in a 6-month egg-feeding trial. The percentage of days of small fish, large fish and meat consumption were assessed through weekly 7-day animal-source food screeners. Grams of intake were assessed through 24-h recalls conducted at 6-9, 9-12 and 12-15 months of age. Plasma ferritin, soluble transferrin receptor (sTfR) and haemoglobin concentrations were measured at 6-9 and 12-15 months of age. Iron biomarkers were adjusted for inflammation during analysis. At enrolment, each flesh food category was consumed by <5% of children in the past 24 h. Over the next 6 months, small fish, large fish and meat were consumed on 25%, 8% and 6% of days, respectively, with mean usual intakes of <5 g/day. More frequent small fish consumption was associated with lower sTfR (geometric mean ratio [95% CI]: 0.98 mg/L [0.96, 1.00] per 10 percentage point difference) but not ferritin (1.03 µg/L [0.98, 1.07]) or haemoglobin (1.01 g/dL [1.00, 1.01]). Large fish consumption was associated with higher anaemia (prevalence ratio [95% CI]: 1.09 [1.01, 1.19]) and lower iron deficiency (0.96 [0.93, 1.00]) prevalence. Gram intakes of flesh food categories were not associated with any iron or anaemia indicators. Small fish were a primary contributor to flesh food intake in this cohort of Malawian children, although usual portions were small. Fish was associated with modest improvements to iron status, but meat was too infrequent to be associated with anaemia and iron deficiency., (© 2024 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Micronutrient deficiency is a common global health problem, and accurately assessing micronutrient biomarkers is crucial for planning and managing effective intervention programs. However, analyzing micronutrient data and applying appropriate cutoffs to define deficiencies can be challenging, particularly when considering the confounding effects of inflammation on certain micronutrient biomarkers. To address this challenge, we developed the Statistical Apparatus of Micronutrient Biomarker Analysis (SAMBA) R package, a new tool that increases ease and accessibility of population-based micronutrient biomarker analysis. The SAMBA package can analyze various micronutrient biomarkers to assess status of iron, vitamin A, zinc, and B vitamins; adjust for inflammation; account for complex survey design when appropriate; and produce reports of summary statistics and prevalence estimates of micronutrient deficiencies using recommended age-specific and sex-specific cutoffs. In this study, we aimed to provide a step-by-step procedure for how to use the SAMBA R package, including how to customize it for broader use, and made both the package and user manual publicly available on GitHub. SAMBA was validated by comparing results by analyzing 24 data sets on nonpregnant women of reproductive age from 23 countries and 30 data sets on preschool-aged children from 26 countries with those obtained by an independent analyst. SAMBA generated identical means, percentiles, and prevalence of micronutrient deficiencies to those calculated by the independent analyst. In conclusion, SAMBA simplifies and standardizes the process for deriving survey-weighted and inflammation-adjusted (when appropriate) estimates of the prevalence of micronutrient deficiencies, reducing the time from data cleaning to result generation. SAMBA is a valuable tool that facilitates the accurate and rapid analysis of population-based micronutrient biomarker data, which can inform public health research, programs, and policy across contexts., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Mineral deficiencies are common in children living in low-resource areas. Eggs are a rich source of essential nutrients and have been shown to improve growth in young children, although little is known about their impact on mineral status. Children aged 6-9 months (n = 660) were randomized to receive either one egg/day for 6-months or no intervention. Anthropometric data, dietary recalls, and venous blood were collected at baseline and 6-months follow-up. Quantification of plasma minerals (n = 387) was done using inductively coupled plasma-mass spectroscopy. Difference-in-difference mean plasma mineral concentrations was determined from baseline and follow-up values and assessed between groups by intention-to-treat using ANCOVA regression models. Prevalence of zinc deficiency was 57.4% at baseline and 60.5% at follow-up. Mean difference (MD) of plasma magnesium, selenium, copper, and zinc levels were not different between groups. Plasma iron concentrations were significantly lower in the intervention compared to the control group (MD = - 9.29; 95% CI: - 15.95, - 2.64). Zinc deficiency was widely prevalent in this population. Mineral deficiencies were not addressed with the egg intervention. Further interventions are needed to improve the mineral status of young children., (© 2023. The Author(s).)

Alkylglycerol monooxygenase (AGMO) and plasmanylethanolamine desaturase (PEDS1) are enzymes involved in ether lipid metabolism. While AGMO degrades plasmanyl lipids by oxidative cleavage of the ether bond, PEDS1 exclusively synthesizes a specific subclass of ether lipids, the plasmalogens, by introducing a vinyl ether double bond into plasmanylethanolamine phospholipids. Ether lipids are characterized by an ether linkage at the sn-1 position of the glycerol backbone and they are found in membranes of different cell types. Decreased plasmalogen levels have been associated with neurological diseases like Alzheimer's disease. Agmo-deficient mice do not present an obvious phenotype under unchallenged conditions. In contrast, Peds1 knockout mice display a growth phenotype. To investigate the molecular consequences of Agmo and Peds1 deficiency on the mouse lipidome, five tissues from each mouse model were isolated and subjected to high resolution mass spectrometry allowing the characterization of up to 2013 lipid species from 42 lipid subclasses. Agmo knockout mice moderately accumulated plasmanyl and plasmenyl lipid species. Peds1-deficient mice manifested striking changes characterized by a strong reduction of plasmenyl lipids and a concomitant massive accumulation of plasmanyl lipids resulting in increased total ether lipid levels in the analyzed tissues except for the class of phosphatidylethanolamines where total levels remained remarkably constant also in Peds1 knockout mice. The rate-limiting enzyme in ether lipid metabolism, FAR1, was not upregulated in Peds1-deficient mice, indicating that the selective loss of plasmalogens is not sufficient to activate the feedback mechanism observed in total ether lipid deficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Vitamin A deficiency (VAD) is common in populations with limited dietary diversity and access to vitamin A-rich foods., Objectives: This analysis aimed to determine the impact of supplementing children's diets with 1 egg/d on the concentration of plasma retinol and RBP and the prevalence of VAD., Methods: Children age 6-9 mo living in the Mangochi district of Malawi were individually randomly assigned to receive 1 egg/d for 6 mo ( n = 331) or continue their usual diet ( n = 329) in the Mazira trial (clinicaltrials.gov; NCT03385252). This secondary analysis measured plasma retinol by HPLC and RBP, CRP, and α-1-acid glycoprotein (AGP) by ELISA techniques at enrollment and 6 mo follow-up. Retinol and RBP were adjusted for inflammation, and mean concentrations were compared between groups using linear regression models. In addition, prevalence ratios of VAD (retinol <0.7 μmol/L) were compared between groups using log-binomial or modified Poisson regression models., Results: After 6 mo of study participation, 489 were assessed for retinol (egg: n = 238; control: n = 251), and 575 (egg: n = 281; control: n = 294) were assessed for RBP. Prevalence of inflammation (CRP >5 mg/L or AGP >1 g/L: 62%) and inflammation-adjusted VAD (7%) at enrollment did not differ between groups. At follow-up, the egg intervention group did not differ from the control in inflammation-adjusted retinol [geometric mean (95% CI); egg: 1.10 μmol/L (1.07, 1.13); control: 1.08 (1.05, 1.12)], RBP [egg: 0.99 μmol/L (0.96, 1.02); control: 0.97 (0.94, 1.00)], or prevalence of VAD [egg: 6%; control: 3%; prevalence ratio: 1.87 (0.83, 4.24)]., Conclusions: Provision of 1 egg/d did not impact VAD, plasma retinol, or RBP among young children in rural Malawi, where the prevalence of VAD was low. Curr Dev Nutr 2023;x:xx.This trial was registered at [clinicaltrials.gov] as [NCT03385252]., (© 2023 The Author(s).)

On the basis of findings that cultured rat hepatocytes secrete lipoprotein with a high plasmalogen content and the occurrence of this lipid in human serum, it has been suggested that hepatocytes play a role in the supply of plasmalogens to tissues. We tested this hypothesis in a mouse with a hepatocyte-specific defect in peroxisomes, an organelle essentially required for plasmalogen biosynthesis. We analyzed plasmalogens in lipid extracts of forebrain, liver and five further tissues and in plasma by reaction with dansylhydrazine in hydrochloric acid, which cleaves the vinyl ether of plasmalogens and forms a fluorescent dansylhydrazone, which we quantified by reversed phase high performance liquid chromatography. Reaction with dansylhydrazine in acetic acid was used to quantify free aldehydes as a control. Our results show normal levels of plasmalogens in plasma and in all tissues examined, including forebrain and the liver, irrespective of the inactivation of hepatic peroxisomes. None of the selected ether lipids analyzed by mass spectrometry in plasma and liver was decreased in the mice deficient in liver peroxisomes. In contrast, we found three plasmenylcholine species which were even significantly increased in the livers of these animals. Quantification of mRNA expression of plasmalogen biosynthetic enzymes revealed particularly low expression of fatty acyl-CoA reductase, the key regulatory enzyme of plasmalogen biosynthesis, in liver, with and without hepatic peroxisome deficiency. Our results do not support the suggested role of hepatocytes in supplying plasmalogens to tissues., Competing Interests: Declarations of interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Due to their unique chemical structure, plasmalogens do not only exhibit distinct biophysical and biochemical features, but require specialized pathways of biosynthesis and metabolization. Recently, major advances have been made in our understanding of these processes, for example by the attribution of the gene encoding the enzyme, which catalyzes the final desaturation step in plasmalogen biosynthesis, or by the identification of cytochrome C as plasmalogenase, which allows for the degradation of plasmalogens. Also, models have been presented that plausibly explain the maintenance of adequate cellular levels of plasmalogens. However, despite the progress, many aspects around the questions of how plasmalogen metabolism is regulated and how plasmalogens are distributed among organs and tissues in more complex organisms like mammals, remain unresolved. Here, we summarize and interpret current evidence on the regulation of the enzymes involved in plasmalogen biosynthesis and degradation as well as the turnover of plasmalogens. Finally, we focus on plasmalogen traffic across the mammalian body - a topic of major importance, when considering plasmalogen replacement therapies in human disorders, where deficiencies in these lipids have been reported. These involve not only inborn errors in plasmalogen metabolism, but also more common diseases including Alzheimer's disease and neurodevelopmental disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dorninger, Werner, Berger and Watschinger.)

Little is known about the physiological role of alkylglycerol monooxygenase (AGMO), the only enzyme capable of cleaving the 1-O-alkyl ether bond of ether lipids. Expression and enzymatic activity of this enzyme can be detected in a variety of tissues including adipose tissue. This labile lipolytic membrane-bound protein uses tetrahydrobiopterin as a cofactor, and mice with reduced tetrahydrobiopterin levels have alterations in body fat distribution and blood lipid concentrations. In addition, manipulation of AGMO in macrophages led to significant changes in the cellular lipidome, and alkylglycerolipids, the preferred substrates of AGMO, were shown to accumulate in mature adipocytes. Here, we investigated the roles of AGMO in lipid metabolism by studying 3T3-L1 adipogenesis. AGMO activity was induced over 11 days using an adipocyte differentiation protocol. We show that RNA interference-mediated knockdown of AGMO did not interfere with adipocyte differentiation or affect lipid droplet formation. Furthermore, lipidomics revealed that plasmalogen phospholipids were preferentially accumulated upon Agmo knockdown, and a significant shift toward longer and more polyunsaturated acyl side chains of diacylglycerols and triacylglycerols could be detected by mass spectrometry. Our results indicate that alkylglycerol catabolism has an influence not only on ether-linked species but also on the degree of unsaturation in the massive amounts of triacylglycerols formed during in vitro 3T3-L1 adipocyte differentiation., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Young children with diets lacking diversity with low consumption of animal source foods are at risk of iron deficiency anemia (IDA)., Objectives: Our objectives were to determine the impact of supplementing diets with 1 egg/d on 1 ) plasma ferritin, soluble transferrin receptor (sTfR), body iron index (BII), and hemoglobin concentrations and 2 ) the prevalence of iron deficiency (ID), anemia, and IDA., Methods: Malawian 6-9-mo-old infants in the Mazira trial (clinicaltrials.gov; NCT03385252) were individually randomly assigned to receive 1 egg/d for 6 mo ( n = 331) or continue their usual diet ( n = 329). In this secondary analysis, hemoglobin, plasma ferritin, sTfR, C-reactive protein (CRP), and α-1-acid glycoprotein (AGP) were measured at enrollment and 6-mo follow-up. Iron biomarkers were corrected for inflammation. Ferritin, sTfR, BII, and hemoglobin were compared between groups using linear regression. Prevalence ratios (PRs) for anemia (hemoglobin <11 g/dL) and ID (ferritin <12 µg/L, sTfR >8.3 mg/L, or BII <0 mg/kg) between groups were compared using log binomial or modified Poisson regression., Results: A total of 585 children were included in this analysis (Egg: n = 286; Control: n = 299). At enrollment, the total prevalence of anemia was 61% and did not differ between groups. At 6-mo follow-up, groups did not differ in geometric mean concentration of hemoglobin [mean (95% CI); Egg: 10.9 (10.7, 11.1) g/dL; Control: 11.1 (10.9, 11.2) g/dL] and inflammation-adjusted ferritin [Egg: 6.52 (5.98, 7.10) µg/L; Control: 6.82 (6.27, 7.42) µg/L], sTfR [Egg: 11.34 (10.92, 11.78) mg/L; Control: 11.46 (11.04, 11.89) mg/L] or BII [Egg: 0.07 (0.06, 0.09) mg/kg; Control: 0.07 (0.05, 0.08) mg/kg]. There were also no group differences in anemia [Egg: 46%; Control 40%; PR: 1.15 (95% CI: 0.96, 1.38)], ID [PR: 0.99 (0.94, 1.05)], or IDA [PR: 1.12 (0.92, 1.36)]., Conclusions: Providing eggs daily for 6 mo did not affect iron status or anemia prevalence in this context. Other interventions are needed to address the high prevalence of ID and anemia among young Malawian children. This trial is registered at http://www.clinicaltrials.gov as NCT03385252., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Typically, glycerophospholipids are represented with two esterified fatty acids. However, by up to 20%, a significant proportion of this lipid class carries an ether-linked fatty alcohol side chain at the sn -1 position, generally referred to as ether lipids, which shape their specific physicochemical properties. Among those, plasmalogens represent a distinct subgroup characterized by an sn -1 vinyl-ether double bond. The total loss of ether lipids in severe peroxisomal defects such as rhizomelic chondrodysplasia punctata indicates their crucial contribution to diverse cellular functions. An aberrant ether lipid metabolism has also been reported in multifactorial conditions including Alzheimer's disease. Understanding the underlying pathological implications is hampered by the still unclear exact functional spectrum of ether lipids, especially in regard to the differentiation between the individual contributions of plasmalogens (plasmenyl lipids) and their non-vinyl-ether lipid (plasmanyl) counterparts. A primary reason for this is that exact identification and quantification of plasmalogens and other ether lipids poses a challenging and usually labor-intensive task. Diverse analytical methods for the detection of plasmalogens have been developed. Liquid chromatography-tandem mass spectrometry is increasingly used to resolve complex lipid mixtures, and with optimized parameters and specialized fragmentation strategies, discrimination between ethers and plasmalogens is feasible. In this review, we recapitulate historic and current methodologies for the recognition and quantification of these important lipids and will discuss developments in this field that can contribute to the characterization of plasmalogens in high structural detail., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Koch, Watschinger, Werner and Keller.)

Plasmalogens are an abundant class of glycerophospholipids in the mammalian body, with special occurrence in the brain and in immune cell membranes. Plasmanylethanolamine desaturase (PEDS1) is the final enzyme of plasmalogen biosynthesis, which introduces the characteristic 1-O-alk-1'-enyl double bond. The recent sequence identification of PEDS1 as transmembrane protein 189 showed that its protein sequence is related to a special class of plant desaturases (FAD4), with whom it shares a motif of 8 conserved histidines, which are essential for the enzymatic activity. In the present work, we wanted to gain more insight into the sequence-function relationship of this enzyme and mutated to alanine additional 28 amino acid residues of murine plasmanylethanolamine desaturase including those 20 residues, which are also totally conserved-in addition to the eight-histidine-motif-among the animal PEDS1 and plant FAD4 plant desaturases. We measured the enzymatic activity by transient transfection of tagged murine PEDS1 expression clones to a PEDS1-deficient human HAP1 cell line by monitoring of labeled plasmalogens formed from supplemented 1-O-pyrenedecyl-sn-glycerol in relation to recombinant protein expression. Surprisingly, only a single mutation, namely aspartate 100, led to a total loss of PEDS1 activity. The second strongest impact on enzymatic activity had mutation of phenylalanine 118, leaving only 6% residual activity. A structural model obtained by homology modelling to available structures of stearoyl-CoA reductase predicted that this aspartate 100 residue interacts with histidine 96, and phenylalanine 118 interacts with histidine 187, both being essential histidines assumed to be involved in the coordination of the di-metal center of the enzyme., (© 2022. The Author(s).)