Activation of Lyt-2+ T cells by antibodies towards brain-associated antigens. I. Accessory cell requirement and role of Fc receptors in the induction of reactivity to interleukin 2

The present report describes a system where essentially all Lyt-2+ T cells are selectively activated by rabbit anti-mouse brain antibodies (RaMB) to interleukin 2 (IL 2) reactivity. High efficiency of RaMB-mediated induction was obtained by a 5 h incubation with antibodies at high cell density of Sephadex G-10-nonadherent spleen cells. No in situ production of IL 2 by RaMB-treated cells was detected, and proliferative responses were entirely dependent on exogeneous IL 2. RaMB-induced IL 2 reactivity was found to require accessory cells which are Fc receptor positive, and clearly distinct from those required to induce T cell proliferation in mixed lymphocyte cultures. We conclude that Lyt-2+ T cells are triggered to IL 2 reactivity by Fc receptor-mediated presentation of RaMB antibodies. The mechanism of induction by RaMB antibodies is discussed.     

Behavioural effects of human fetal dopamine neurons grafted in a rat model of Parkinson's disease

Summary The ventral mesencephalon, containing the developing dopaminergic neurons of the substantia nigra-ventral tegmental region, was obtained from aborted human fetuses of 9–19 weeks of gestation. The tissue was grafted into the striatum of rats previously subjected to a 6-hydroxydopamine lesion of the mesostriatal dopamine pathway. The graft recipients were immunosuppressed by daily injections of Cyclosporin A. Amphetamine-induced motor asymmetry was reduced, and finally totally reversed, only in rats receiving grafts from the 9-week old fetal donor. The fluorescence microscopic analysis revealed large numbers of surviving dopamine neurons, and extensive fiber outgrowth into the host striatum, in these rats. By contrast, rats receiving grafts from 11–19 week old donors had at most only few surviving dopamine neurons. These results indicate that human fetal mesencephalic tissue may be an efficient source of dopamine neurons for functional intracerebral grafting in patients with Parkinson's disease.A preliminary account of some of the results from this study was presented at the New York Academy of Sciences meeting on Cell and tissue transplantation into the adult brain, New York, April 4, 1986     

Pharmacokinetics and effects on blood pressure of a single oral dose of milrinone in healthy subjects and in patients with renal impairment

Summary Milrinone, a new, nonglycosidic inotropic agent with peripheral vasodilating properties, was given as a single oral 5 mg dose to 7 healthy subjects, 7 patients with moderate renal impairment (CRI I, creatinine clearance 30–63 ml/min) and 7 patients with severe renal impairment (CRI II, creatinine clearance 9–29 ml/min). All except one of the patients with renal impairment had hypertension. The mean urinary recovery of milrinone was 82% in healthy subjects, the renal clearance was 288 ml/min and the plasma half-life (t_1/2) was 0.94 h. In CRI the mean plasma t_1/2 was prolonged (CRI I 1.78 h, CRI II 3.24 h). There was a significant linear relationship between creatinine clearance and the elimination rate constant, and between creatinine clearance and the renal clearance of milrinone. During the study day there was a tendency to a decrease in supine BP from 1 to 6–8 h after dosing, with the maximal decrease at 2–3 h (healthy subjects 118/71107/56, CRI 159/95136/79 mmHg). The same degree of change was seen in standing BP. A slight rise in standing HR was seen from 2–6 h after dosing. Changes in BP and HR are difficult to evaluate since the study was not placebo-controlled.The plasma elimination rate of milrinone was decreased in CRI and dose adjustment may be necessary. Placebo-controlled studies of milrinone in hypertensive patients would be required to validate its possible antihypertensive effect.     

Muscle and plasma carnitine levels and urinary carnitine excretion in multiply injured patients on total parenteral nutrition

Carnitine is necessary for the transport of long-chain fatty acids across the mitochondrial membrane. Thirteen severely injured patients on total parenteral nutrition were studied during days 2-8 post injury. Initially plasma and skeletal muscle carnitine values were within the range earlier found for normal subjects, whereas the urinary carnitine excretion was markedly increased. On day 4 there was a simultaneous decrease in the carnitine concentration in plasma (alpha < 0.01) and urine (alpha < 0.05) as well as in skeletal muscle tissue (alpha < 0.05 using only the values that could be paired i.e. from eight subjects), whereas no difference was found between day 2 and 8. One explanation of this pattern might be that a redistribution of carnitine occurs to other organs not measured, for example the liver. In skeletal muscle tissue, statistically significant positive correlations were found between the carnitine level and ATP (alpha < 0.01) and phosphocreatine (alpha < 0.02) as well as between carnitine and glycogen (alpha < 0.05).     

Dietary Supplementation with Selenium and Coenzyme Q10 Prevents Increase in Plasma D-Dimer While Lowering Cardiovascular Mortality in an Elderly Swedish Population

A low intake of selenium is associated with increased cardiovascular mortality. This could be reduced by supplementation with selenium and coenzyme Q₁₀. D-dimer, a fragment of fibrin mirroring fibrinolysis, is a biomarker of thromboembolism, increased inflammation, endothelial dysfunction and is associated with cardiovascular mortality in ischemic heart disease. The objective was to examine the impact of selenium and coenzyme Q₁₀ on the level of D-dimer, and its relationship to cardiovascular mortality. D-dimer was measured in 213 individuals at the start and after 48 months of a randomised double-blind placebo-controlled trial with selenium yeast (200 µg/day) and coenzyme Q₁₀ (200 mg/day) (n = 106) or placebo (n = 107). The follow-up time was 4.9 years. All included individuals were low in selenium (mean 67 μg/L, SD 16.8). The differences in D-dimer concentration were evaluated by the use of T-tests, repeated measures of variance and ANCOVA analyses. At the end, a significantly lower D-dimer concentration was observed in the active treatment group in comparison with those on placebo (p = 0.006). Although D-dimer values at baseline were weakly associated with high-sensitive CRP, while being more strongly associated with soluble tumour necrosis factor receptor 1 and sP-selectin, controlling for these in the analysis there was an independent effect on D-dimer. In participants with a D-dimer level above median at baseline, the supplementation resulted in significantly lower cardiovascular mortality compared to those on placebo (p = 0.014). All results were validated with a persisting significant difference between the two groups. Therefore, supplementation with selenium and coenzyme Q₁₀ in a group of elderly low in selenium and coenzyme Q₁₀ prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group. The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.     

Effects of Anthocyanin on Intestinal Health: A Systematic Review

Intestinal health relies on the association between the mucosal immune system, intestinal barrier and gut microbiota. Bioactive components that affect the gut microbiota composition, epithelial physical barrier and intestinal morphology were previously studied. The current systematic review evaluated evidence of anthocyanin effects and the ability to improve gut microbiota composition, their metabolites and parameters of the physical barrier; this was conducted in order to answer the question: “Does food source or extract of anthocyanin promote changes on intestinal parameters?”. The data analysis was conducted following the PRISMA guidelines with the search performed at PubMed, Cochrane and Scopus databases for experimental studies, and the risk of bias was assessed by the SYRCLE tool. Twenty-seven studies performed in animal models were included, and evaluated for limitations in heterogeneity, methodologies, absence of information regarding allocation process and investigators’ blinding. The data were analyzed, and the anthocyanin supplementation demonstrated positive effects on intestinal health. The main results identified were an increase of Bacteroidetes and a decrease of Firmicutes, an increase of short chain fatty acids production, a decrease of intestinal pH and intestinal permeability, an increase of the number of goblet cells and tight junction proteins and villi improvement in length or height. Thus, the anthocyanin supplementation has a potential effect to improve the intestinal health. PROSPERO (CRD42020204835).     

Quantifying convergence on health-related indicators of the 2030 agenda for sustainable development

The extended scope and complexity of the United Nations 2030 agenda entail important challenges for the operationalization of the health-related sustainable development goal (SDG) indicators. Divergences in concepts, agendas and implementation strategies among institutions have fostered the parallel development of alternative and concurrent indicators. We aim to determine the convergences and divergences between five key institutions: the Global Burden of Disease Study (GBD), the Pan American Health Organization, the Sustainable Development Solutions Network, the World Bank and the World Health Organization (WHO). Of the 104 health-related indicators listed by these five institutions, 60 are consistent with official Inter-agency and Expert Group SDG indicators. Our analysis considers the indicators included, and the themes these indicators cover, in each institution list and each institution online platform. We quantified convergence in indicators between the institutions themselves, but also between the institutions and the official Inter-agency and Expert Group. Our results indicate important divergences; only 22 of the 60 indicators are included in the lists of all five institutions. The level of adoption of the official metrics varies from 40.5% (15/(47−10)) for the GBD to 86.2% (25/(29−0)) for the World Bank. WHO, the official curator of the Inter-agency and Expert Group SDG indicators, is only convergent with the official metrics by 72.1% (31/(45−2)). Our analysis, and the resulting awareness of the differences, potentialities and limitations of indicators and platforms, provides important contributions to enable the achievement of the health-related SDGs and deliver the promise of the 2030 agenda.     

Two screening instruments for collecting alcohol-related information from expectant mothers and fathers: Testing the reliability of the Parent Alcohol Screening Questionnaire and the Social Support for an Alcohol-Free Pregnancy Questionnaire

The aim is to test the reliability of two alcohol screening instruments: (1) The Parent Alcohol Screening Questionnaire (PASQ5), and (2) the Social Support for an Alcohol-free Pregnancy (SSAFP) questionnaire. This is a cohort study from the south of Sweden using repeated surveys during pregnancy. To examine if responses differed according to different data collection methods, two cohorts consisting of 289 expectant mothers and 141 fathers completed the PASQ5 both verbally (weeks 6–7) and in writing (week 12) within regular antenatal visits. One of the cohorts (n = 137/64) also completed the SSAFP in week 12 and later in week 33. The third cohort, consisting of 179 and 133 expectant mothers and fathers, respectively, completed the PASQ5 and the SSAFP twice in late pregnancy (week 31 + 33). Eight of 10 items in the PASQ5 were stable for both expectant mothers and expectant fathers when comparing verbal versus written-delivered formats. Eight of 10 questions in the PASQ5 were stable when assessing the items in a test–retest analysis in late pregnancy for expectant mothers and nine of 10 questions were stable for fathers. The SSAFP items showed high internal consistency (0.86) for expectant mothers and excellent internal consistency (0.94) for expectant fathers. Most SSAFP items (17 of 21 for expectant mothers and 18 of 22 for expectant fathers) were also stable in a test–retest scenario in late pregnancy. Both the PASQ5 and SSAFP are reliable tools and may be helpful for clinicians who aim to have a deeper dialogue about alcohol consumption during pregnancy. These tools may also be helpful for researchers aiming to better understand a person's changes in alcohol intake and/or their social support network.