Double aortic arch with double aneuploidy—rare anomaly in combined Down and Klinefelter syndrome

A 14-month-old boy with double aneuploidy and a double aortic arch suffered from frequently recurrent severe feeding and respiratory problems. Chromosomal analysis showed a 48,XXY + 21 karyotype: a double aneuploidy of Down syndrome (DS) and Klinefelter syndrome (KS). Only four cases of double aneuploidy (DS + KS) associated with congenital heart defects have been published of which none had a double aortic arch. Our case report should draw attention to the possibility of a double aortic arch in patients with severe feeding and respiratory problems and a double aneuploidy

Vitamin D Status Is Positively Correlated with Regulatory T Cell Function in Patients with Multiple Sclerosis

In several autoimmune diseases, including multiple sclerosis (MS), a compromised regulatory T cell (Treg) function is believed to be critically involved in the disease process. In vitro, the biologically active metabolite of vitamin D has been shown to promote Treg development. A poor vitamin D status has been linked with MS incidence and MS disease activity. In the present study, we assess a potential in vivo correlation between vitamin D status and Treg function in relapsing remitting MS (RRMS) patients.Serum levels of 25-hydroxyvitamin D (25(OH)D) were measured in 29 RRMS patients. The number of circulating Tregs was assessed by flow-cytometry, and their functionality was tested in vitro in a CFSE-based proliferation suppression assay. Additionally, the intracellular cytokine profile of T helper cells was determined directly ex-vivo by flow-cytometry. Serum levels of 25(OH)D correlated positively with the ability of Tregs to suppress T cell proliferation (R = 0.590, P = 0.002). No correlation between 25(OH)D levels and the number of Tregs was found. The IFN-gamma/IL-4 ratio (Th1/Th2-balance) was more directed towards IL-4 in patients with favourable 25(OH)D levels (R = -0.435, P = 0.023).These results show an association of high 25(OH)D levels with an improved Treg function, and with skewing of the Th1/Th2 balance towards Th2. These findings suggest that vitamin D is an important promoter of T cell regulation in vivo in MS patients. It is tempting to speculate that our results may not only hold for MS, but also for other autoimmune diseases. Future intervention studies will show whether modulation of vitamin D status results in modulation of the T cell response and subsequent amelioration of disease activity

Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis

Background: A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS). Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS) patients. In the present study, we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures. Methodology/Principal Findings: Fifteen RRMS patients were supplemented with 20 000 IU/d vitamin D3 for 12 weeks. Vitamin D and calcium metabolism were carefully monitored, and T cell characteristics were studied by flowcytometry. All patients finished the protocol without side-effects, hypercalcaemia, or hypercalciuria. The median vitamin D status increased from 50 nmol/L (31-175) at week 0 to 380 nmol/L (151-535) at week 12 (P<0.001). During the study, 1 patient experienced an exacerbation of MS and was censored from the T cell analysis. The proportions of (naïve and memory) CD4+ Tregs remained unaffected. Although Treg suppressive function improved in several subjects, this effect was not significant in the total cohort (P = 0.143). An increased proportion of IL-10+ CD4+ T cells was found after supplementation (P = 0.021). Additionally, a decrease of the ratio between IFN-γ+ and IL-4+ CD4+ T cells was observed (P = 0.035). Conclusion/Significance: Twelve week supplementation of high dose vitamin D3 in RRMS patients was well tolerated and did not induce decompensation of calcium metabolism. The skewing towards an anti-inflammatory cytokine profile supports the evidence on vitamin D as an immune-modulator, and may be used as outcome measure for upcoming randomized placebo-controlled trials

Safety and T Cell Modulating Effects of High Dose Vitamin D-3 Supplementation in Multiple Sclerosis

BACKGROUND: A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS). Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS) patients. In the present study, we studied the effects of high dose vitamin D(3) supplementation on safety and T cell related outcome measures. METHODOLOGY/PRINCIPAL FINDINGS: Fifteen RRMS patients were supplemented with 20 000 IU/d vitamin D(3) for 12 weeks. Vitamin D and calcium metabolism were carefully monitored, and T cell characteristics were studied by flowcytometry. All patients finished the protocol without side-effects, hypercalcaemia, or hypercalciuria. The median vitamin D status increased from 50 nmol/L (31–175) at week 0 to 380 nmol/L (151–535) at week 12 (P<0.001). During the study, 1 patient experienced an exacerbation of MS and was censored from the T cell analysis. The proportions of (naïve and memory) CD4(+) Tregs remained unaffected. Although Treg suppressive function improved in several subjects, this effect was not significant in the total cohort (P = 0.143). An increased proportion of IL-10(+) CD4(+) T cells was found after supplementation (P = 0.021). Additionally, a decrease of the ratio between IFN-γ(+) and IL-4(+) CD4(+) T cells was observed (P = 0.035). CONCLUSION/SIGNIFICANCE: Twelve week supplementation of high dose vitamin D(3) in RRMS patients was well tolerated and did not induce decompensation of calcium metabolism. The skewing towards an anti-inflammatory cytokine profile supports the evidence on vitamin D as an immune-modulator, and may be used as outcome measure for upcoming randomized placebo-controlled trials. TRIAL REGISTRATION: Clinicaltrials.gov NCT0094071

The impact of beetroot juice supplementation on muscular endurance, maximal strength and countermovement jump performance

Purpose: Dietary nitrate has been shown to enhance muscle contractile function and has, therefore, been linked to increased muscle power and sprint exercise performance. However, the impact of dietary nitrate supplementation on maximal strength, performance and muscular endurance remains to be established. Methods: Fifteen recreationally active males (25 ± 4 y, BMI 24 ± 3 kg/m2) participated in a randomized double-blinded cross-over study comprising two 6-d supplementation periods; 140 mL/d nitrate-rich (BR; 985 mg/d) and nitrate-depleted (PLA; 0.37 mg/d) beetroot juice. Three hours following the last supplement, we assessed countermovement jump (CMJ) performance, maximal strength and power of the upper leg by voluntary isometric (30° and 60° angle) and isokinetic contractions (60, 120, 180 and 300°·s−1), and muscular endurance (total workload) by 30 reciprocal isokinetic voluntary contractions at 180°·s−1. Results: Despite differences in plasma nitrate (BR: 879 ± 239 vs. PLA: 33 ± 13 μmol/L, P  0.50 for both angles) and isokinetic knee extension power (P > 0.33 for all velocities) did not differ between treatments. Isokinetic knee flexion power was significantly higher following BR compared with PLA ingestion at 60°·s−1 (P = 0.001), but not at 120°·s−1 (P = 0.24), 180°·s−1 (P = 0.066), and 300°·s−1 (P = 0.36). Conclusion: Nitrate supplementation does not improve maximal strength, countermovement jump performance and muscular endurance in healthy, active males

Results proliferation suppression assay.

<p>(A) Representative dot-plot of the sorting protocol. CD25⁺CD127⁻ cells within the CD4⁺ lymphogate were sorted as Tregs, CD25⁻ cells were sorted as Tresps. (B) The percentages of suppression which were achieved for the respective Treg/Tresp ratios of the individual patients are shown. The Treg/Tresp ratio at which 50% inhibition of proliferation was achieved is defined as ED50 of suppression. The distribution of ED50 is shown in the rightmost column. The lines show the median values. The closed dots represent the Beta Interferon-treated patients, the open dots the untreated patients.</p