On supplementing the selenium intake of New Zealanders

1978 ◽  
Vol 39 (3) ◽  
pp. 589-600 ◽  
Author(s):  
Marion F. Robinson ◽  
Heather M. Rea ◽  
Gaylene M. Friend ◽  
R. D. H. Stewart ◽  
P. C. Snow ◽  
...  

1. The daily intake of selenium by three subjects was supplemented with 100 μg Se as selenomethionine (Semet-Se) or sodium selenite (selenite-Se)/d for 10–11 weeks, or with 65 μg Se as in mackerel (Scomber japonicus) (fish-Se)/d for 4 weeks.2. Urinary and faecal excretion of Se was measured and also Se concentration in whole blood, plasma and erythrocytes. Measurements on blood were made at intervals after supplementation had ceased.3. Selenite-Se was not as well absorbed (0.46 of the intake) during the first 4 weeks as Semet-Se (0.75 of the intake) and fish Se (0.66 of the intake).4. Blood Se increased steadily with Semet-Se, from 0.08 to 0.18 μg Se/ml, but more slowly with selenite-Se, reaching a plateau in 7–8 weeks at 0.11 μg Se/ml. Plasma Se increased more rapidly with Semet-Se than with selenite-Se, so that initially with Semet-Se plasma Se was greater than erythrocyte Se.5. Daily urinary excretion increased with all forms of supplement, with initially a greater proportion of absorbed selenite-Se being excreted than Semet-Se or fish-Se. A close relationship was found between plasma Se and 24 h urinary excretion. The findings suggested that there was a rapid initial excretion of presumably unbound Se then a slower excretion of residual unbound, loosely bound or bound Se.6. Total retentions of 3.5 mg selenite-Se and 4.5 mg Semet-Se were large when compared with an estimate of body content of 6 mg Se, derived in another paper (Stewart, Griffiths, Thomson & Robinson, 1978). Retentions of Semet-Se and fish-Se appeared to be reflected in blood Se, whereas for selenite-Se, blood Se reflected retention for only a short period after which Se appeared to be retained without altering the blood Se. This suggested that Semet-Se and selenite-Se were metabolized differently.7. A double blind-dosing trial with 100 μg Semet-Se was carried out for 12 weeks on twenty-four patients with muscular complaints in Tapanui, a low-Se-soil area. Blood Se increased in the experimental group (from 0.067 to 0.143 μg Se/ml); clinical findings were not conclusive and will be presented elsewhere.8. Blood Se was measured in New Zealand residents before travelling to Europe or to North America. On return their blood Se was increased, and depending upon the period of time spent outside New Zealand some values reached concentrations found in visitors and new settlers to New Zealand.9. The results from these studies and the earlier studies of single and multiple dosing have been used to look at the various criteria in use for assessing Se status of subjects. It is suggested that plasma Se be used in preference to 24 h urinary excretion, and in addition to whole blood Se and glutathione peroxidase (EC 1.11.1.9) activity.

1997 ◽  
Vol 77 (4) ◽  
pp. 551-563 ◽  
Author(s):  
Marion F. Robinson ◽  
Christine D. Thomson ◽  
Christopher P. Jenkinson ◽  
Gu Luzhen ◽  
Philip D Whanger

Thirty-six New Zealand women aged between 18 and 23 years received daily for 32 weeks, 200 µg Se as Se-enriched yeast (selenomethionine, SeMet), or brewer's yeast mixed with selenate, or no added Se (placebo) in a double-blind trial. Mean daily Se excretion increased with both supplements; the selenate group excreted more than the SeMet group, 123v. 66 µg/d respectively at week 2, equivalent to 57v. 27 % of the dose. Thereafter Se output increased for the SeMet group reaching a plateau at about 100 µg/d at week 16, when plasma Se had also plateaued at 190 ng/ml. The selenate group had reached an earlier plateau of 110 ng Se/ml at week 7. There was a close relationship between 24 h urine and plasma Se for the SeMet group but not for the selenate group. Renal plasma clearances showed two distinctly different responses; the clearance of 0·4 ml/min reached by the SeMet group at week 2 plateaued as plasma Se increased almost 2-fold; whereas for the selenate group the clearance varied between 0·8 and 1·1 ml/min whilst plasma Se remained almost constant at 110 ng/ml. Previous studies, also of 200 µgSe/d as Se-rich bread, in New Zealand (NZ) and elsewhere showed similar responses to Se-yeast; the selenite response was intermediate between selenate and Se-yeast (SeMet). The full significance of these studies awaits identification of Se components in plasma, glomerular filtrate and urine; meanwhile renal clearances serve as a pointer to changes in the distribution of Se-containing fractions in the plasma. Trimethylselenonium was detected in basal urines, and was a minor component in urines of supplemented NZ subjects at about 1 % of the total Se.


1993 ◽  
Vol 69 (2) ◽  
pp. 577-588 ◽  
Author(s):  
Christine D. Thomson ◽  
Marion F. Robinson ◽  
Judy A. Butler ◽  
Phllip D. Whanger

Thirty-three New Zealand women aged 18–23 years received daily for 32 weeks, 200 μg Se as Seenriched yeast (selenomethionine), or brewer's yeast mixed with selenate, or no added Se (placebo) in a double-blind trial. Se supplementation raised (P= 0.001), platelet glutathione peroxidase (EC1.11.1.9; GSHPx) activity, and also Se and GSHPx in whole blood, erythrocytes and plasma. Selenomethionine was more effective in raising blood Se concentrations than selenate, but both were equally effective in raising GSHPx activities in whole blood, erythrocytes and plasma, indicating a similar bioavailability for the two forms. These observations and those of gel filtration studies of erythrocytes and plasma proteins reported elsewhere (Butleret al.1991) are consistent with the incorporation of Se from selenomethionine into a general tissue protein pool while selenate is directly available for GSHPx synthesis, and explain the poorer correlation between Se and GSHPx in individuals with higher Se status. However, selenate raised platelet GSHPx activities to a greater extent than did selenomethionine suggesting some other effect of selenate on platelets which needs further investigation. A response of GSHPx activity in these New Zealand subjects indicates that their dietary Se intake is insufficient to meet recommended intakes based on the criterion of saturation of GSHPx activity, and could reflect a marginal Se status. The level of blood Se necessary for saturation of GSHPx of about 100 ng Se/ml whole blood confirms observations in earlier studies.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 12.2-12
Author(s):  
I. Muller ◽  
M. Verhoeven ◽  
H. Gosselt ◽  
M. Lin ◽  
T. De Jong ◽  
...  

Background:Tocilizumab (TCZ) is a monoclonal antibody that binds to the interleukin 6 receptor (IL-6R), inhibiting IL-6R signal transduction to downstream inflammatory mediators. TCZ has shown to be effective as monotherapy in early rheumatoid arthritis (RA) patients (1). However, approximately one third of patients inadequately respond to therapy and the biological mechanisms underlying lack of efficacy for TCZ remain elusive (1). Here we report gene expression differences, in both whole blood and peripheral blood mononuclear cells (PBMC) RNA samples between early RA patients, categorized by clinical TCZ response (reaching DAS28 < 3.2 at 6 months). These findings could lead to identification of predictive biomarkers for TCZ response and improve RA treatment strategies.Objectives:To identify potential baseline gene expression markers for TCZ response in early RA patients using an RNA-sequencing approach.Methods:Two cohorts of RA patients were included and blood was collected at baseline, before initiating TCZ treatment (8 mg/kg every 4 weeks, intravenously). DAS28-ESR scores were calculated at baseline and clinical response to TCZ was defined as DAS28 < 3.2 at 6 months of treatment. In the first cohort (n=21 patients, previously treated with DMARDs), RNA-sequencing (RNA-seq) was performed on baseline whole blood PAXgene RNA (Illumina TruSeq mRNA Stranded) and differential gene expression (DGE) profiles were measured between responders (n=14) and non-responders (n=7). For external replication, in a second cohort (n=95 therapy-naïve patients receiving TCZ monotherapy), RNA-seq was conducted on baseline PBMC RNA (SMARTer Stranded Total RNA-Seq Kit, Takara Bio) from the 2-year, multicenter, double-blind, placebo-controlled, randomized U-Act-Early trial (ClinicalTrials.gov identifier: NCT01034137) and DGE was analyzed between 84 responders and 11 non-responders.Results:Whole blood DGE analysis showed two significantly higher expressed genes in TCZ non-responders (False Discovery Rate, FDR < 0.05): urotensin 2 (UTS2) and caveolin-1 (CAV1). Subsequent analysis of U-Act-Early PBMC DGE showed nine differentially expressed genes (FDR < 0.05) of which expression in clinical TCZ non-responders was significantly higher for eight genes (MTCOP12, ZNF774, UTS2, SLC4A1, FECH, IFIT1B, AHSP, and SPTB) and significantly lower for one gene (TND2P28M). Both analyses were corrected for baseline DAS28-ESR, age and gender. Expression of UTS2, with a proposed function in regulatory T-cells (2), was significantly higher in TCZ non-responders in both cohorts. Furthermore, gene ontology enrichment analysis revealed no distinct gene ontology or IL-6 related pathway(s) that were significantly different between TCZ-responders and non-responders.Conclusion:Several genes are differentially expressed at baseline between responders and non-responders to TCZ therapy at 6 months. Most notably, UTS2 expression is significantly higher in TCZ non-responders in both whole blood as well as PBMC cohorts. UTS2 could be a promising target for further analyses as a potential predictive biomarker for TCZ response in RA patients in combination with clinical parameters (3).References:[1]Bijlsma JWJ, Welsing PMJ, Woodworth TG, et al. Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet. 2016;388(10042):343-55.[2]Bhairavabhotla R, Kim YC, Glass DD, et al. Transcriptome profiling of human FoxP3+ regulatory T cells. Human Immunology. 2016;77(2):201-13.[3]Gosselt HR, Verhoeven MMA, Bulatovic-Calasan M, et al. Complex machine-learning algorithms and multivariable logistic regression on par in the prediction of insufficient clinical response to methotrexate in rheumatoid arthritis. Journal of Personalized Medicine. 2021;11(1).Disclosure of Interests:None declared


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Javier Fernández-López ◽  
M. Teresa Telleria ◽  
Margarita Dueñas ◽  
Mara Laguna-Castro ◽  
Klaus Schliep ◽  
...  

AbstractThe use of different sources of evidence has been recommended in order to conduct species delimitation analyses to solve taxonomic issues. In this study, we use a maximum likelihood framework to combine morphological and molecular traits to study the case of Xylodon australis (Hymenochaetales, Basidiomycota) using the locate.yeti function from the phytools R package. Xylodon australis has been considered a single species distributed across Australia, New Zealand and Patagonia. Multi-locus phylogenetic analyses were conducted to unmask the actual diversity under X. australis as well as the kinship relations respect their relatives. To assess the taxonomic position of each clade, locate.yeti function was used to locate in a molecular phylogeny the X. australis type material for which no molecular data was available using morphological continuous traits. Two different species were distinguished under the X. australis name, one from Australia–New Zealand and other from Patagonia. In addition, a close relationship with Xylodon lenis, a species from the South East of Asia, was confirmed for the Patagonian clade. We discuss the implications of our results for the biogeographical history of this genus and we evaluate the potential of this method to be used with historical collections for which molecular data is not available.


2012 ◽  
Vol 6 ◽  
pp. CMPed.S9349
Author(s):  
J. Uberos ◽  
V. Fernéndez-Puentes ◽  
M. Molina-Oya ◽  
R. Rodrïguez-Belmonte ◽  
A. Ruïz-López ◽  
...  

Objectives The present study, which is part of the ISRCTN16968287 clinical assay, is aimed at determining the effects of cranberry syrup or trimethoprim treatment for UTI. Methods This Phase III randomised clinical trial was conducted at the San Cecilio Clinical Hospital (Granada, Spain) with a study population of 192 patients, aged between 1 month and 13 years. Criteria for inclusion were a background of recurrent UTI, associated or otherwise with vesico-ureteral reflux of any degree, or renal pelvic dilatation associated with urinary infection. Each child was randomly given 0.2 mL/Kg/day of either cranberry syrup or trimethoprim (8 mg/mL). The primary and secondary objectives, respectively, were to determine the risk of UTI and the levels of phenolic acids in urine associated with each intervention. Results With respect to UTI, the cranberry treatment was non-inferior to trimethoprim. Increased urinary excretion of ferulic acid was associated with a greater risk of UTI developing in infants aged under 1 year (RR 1.06; CI 95% 1.024–1.1; P = 0.001). Conclusions The results obtained show the excretion of ferulic acid is higher in infants aged under 1 year, giving rise to an increased risk of UTI, for both treatment options.


2015 ◽  
Vol 113 (3) ◽  
pp. 426-434 ◽  
Author(s):  
Bobbi Langkamp-Henken ◽  
Cassie C. Rowe ◽  
Amanda L. Ford ◽  
Mary C. Christman ◽  
Carmelo Nieves ◽  
...  

Acute psychological stress is positively associated with a cold/flu. The present randomised, double-blind, placebo-controlled study examined the effect of three potentially probiotic bacteria on the proportion of healthy days over a 6-week period in academically stressed undergraduate students (n 581) who received Lactobacillus helveticus R0052, Bifidobacterium longum ssp. infantis R0033, Bifidobacterium bifidum R0071 or placebo. On each day, participants recorded the intensity (scale: 0 = not experiencing to 3 = very intense) for nine cold/flu symptoms, and a sum of symptom intensity >6 was designated as a day of cold/flu. B. bifidum resulted in a greater proportion of healthy days than placebo (P≤ 0·05). The percentage of participants reporting ≥ 1 d of cold/flu during the 6-week intervention period was significantly lower with B. bifidum than with placebo (P< 0·05). There were no effects of B. infantis or L. helveticus compared with placebo on either outcome. A predictive model accounted for influential characteristics and their interactions on daily reporting of cold/flu episodes. The proportion of participants reporting a cold on any given day was lower at weeks 2 and 3 with B. bifidum and B. infantis than with placebo for the average level of stress and the most commonly reported number of hours of sleep. Daily intake of bifidobacteria provides benefit related to cold/flu outcomes during acute stress.


Author(s):  
Hironori Nakagami

Abstract There is currently an outbreak of respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus disease 2019 (COVID-19) is caused by infection with SARS-CoV-2. Individuals with COVID-19 have symptoms that are usually asymptomatic or mild in most initial cases. However, in some cases, moderate and severe symptoms have been observed with pneumonia. Many companies are developing COVID-19 vaccine candidates using different technologies that are classified into four groups (intact target viruses, proteins, viral vectors and nucleic acids). For rapid development, RNA vaccines and adenovirus vector vaccines have been urgently approved, and their injection has already started across the world. These types of vaccine technologies have been developed over more than 20 years using translational research for use against cancer or diseases caused by genetic disorders but the COVID-19 vaccines are the first licensed drugs to prevent infectious diseases using RNA vaccine technology. Although these vaccines are highly effective in preventing COVID-19 for a short period, safety and efficiency evaluations should be continuously monitored over a long time period. As the time of writing, more than 10 projects are now in phase 3 to evaluate the prevention of infection in double-blind studies. Hopefully, several projects may be approved to ensure high-efficiency and safe vaccines.


PEDIATRICS ◽  
1980 ◽  
Vol 65 (5) ◽  
pp. 1010-1012
Author(s):  
John D. Lloyd-Still ◽  
Howard E. Ganther

Whole blood selenium and glutathione peroxidase levels were measured in 20 infants and children (aged 6 months to 15 years) with cystic fibrosis. The whole blood selenium concentration in cystic fibrosis was 0.122 ± 0.025 µg/gm. Although the levels of selenium in cystic fibrosis children were below the levels found in a study of healthy children (0.223 ± 0.007 µg/gm), they are comparable to those found in children with phenylketonuria treated dietetically and exceed the blood selenium level of healthy children in New Zealand. Levels of the selenoenzyme glutathione peroxidase in children with cystic fibrosis (0.042 ± 0.007 units/mg Hb) were in the normal range (0.035 ± 0.003 units/mg of Hb). These results do not support the hypothesis that deficiency of selenium is responsible for cystic fibrosis.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Steven C Cramer ◽  
Lori A Enney ◽  
Colleen K Russell ◽  
Monica Simeoni ◽  
Thomas R Thompson

Introduction: One class of potential post-stroke restorative therapy focuses on promoting axon outgrowth by blocking myelin-based inhibitory proteins such as myelin-associated glycoprotein (MAG). The aim of the current study was to extend preclinical and clinical findings of GSK249320, an IgG1-type monoclonal antibody to MAG, to explore effects on motor outcomes after stroke. Methods: This was a phase IIb double-blind, randomized, placebo controlled study (GSK funded; clinicaltrials.gov # NCT01808261). At 30 international sites, patients with ischemic stroke 24-72 hours prior and deficits in gait were randomized to two IV infusions of GSK249320 or placebo. Primary outcome measure was change in gait velocity from baseline to Day 90. Results: A total of 134 subjects were randomized. The two groups were overall well matched at baseline. The study was stopped at the pre-specified interim analysis because the treatment difference met the predefined futility criteria cutoff. Secondary endpoints, including gait analyzed categorically and upper extremity function (Box & Blocks score), were concordant. The two IV infusions of GSK249320 were well tolerated. Although direct evidence that the therapy reached the biological target was not available, indirect evidence of target binding was suggested by the substantial reduction in free MAG plasma levels with GSK249320 treatment. Conclusions: The monoclonal antibody GSK249320 administered IV within 72 hours of stroke onset demonstrated no improvement in gait velocity as compared to placebo. The antibody was well tolerated and showed low immunogenicity, findings that may prove useful to future studies aiming to use a monoclonal antibody to modify activity in specific biological pathways in order to improve recovery from stroke.


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