scholarly journals Long-term sex-differential effects of neonatal vitamin A supplementation on in vitro cytokine responses

2017 ◽  
Vol 118 (11) ◽  
pp. 942-948
Author(s):  
Kristoffer J. Jensen ◽  
Mia J. Søndergaard ◽  
Andreas Andersen ◽  
Cesario Martins ◽  
Christian Erikstrup ◽  
...  

AbstractHigh-dose vitamin A supplementation (VAS) may affect mortality to infectious diseases in a sex-differential manner. Here, we analysed the long-term immunological effects of neonatal vitamin A supplementation (NVAS) in 247 children, who had been randomly allocated to 50 000 or 25 000 IU vitamin A (15mg and 7·5mg retinol equivalents, respectively) or placebo at birth. At 4–6 months of age, we assessed bacille Calmette–Guérin (BCG) scarification, and we analysed in vitro responses of TNF-α, IL-5, IL-10, IL-13 and IFN-γ in whole blood stimulations to phytohaemagglutinin (PHA), purified protein derivative (PPD), tetanus toxoid and lipopolysaccharide. There were no differences between the two doses of NVAS, and thus they were analysed combined as NVAS (any dose) v. placebo. All analyses were performed unstratified and by sex. NVAS increased the chance of having a scar after BCG vaccination in females (NVAS v. placebo: 96 v. 71 %, proportion ratio: 1·24; 95 % CI 1·09, 1·42), but not in males (Pfor interaction=0·012). NVAS was associated with significant sex-differential effects on the pro- to anti-inflammatory cytokine ratios (TNF-α:IL-10) to PPD, tetanus toxoid and medium alone, which were increased in females but decreased in males. In addition, IL-17 responses tended to be increased in NVAS v. placebo recipients in males but not in females, significantly so for the PHA stimulation. The study corroborates sex-differential effects of VAS on the immune system, emphasising the importance of analysing VAS effects by sex.

2007 ◽  
Vol 98 (2) ◽  
pp. 422-430 ◽  
Author(s):  
R. A. Ayah ◽  
D. L. Mwaniki ◽  
P. Magnussen ◽  
A. E. Tedstone ◽  
T. Marshall ◽  
...  

Postpartum vitamin A supplementation of mothers and infants is recommended, but the efficacy has been questioned. In this double-blind, placebo-controlled trial, Kenyan mother–infant pairs were randomised to maternal vitamin A (400 000 IU) or placebo < 24 h postpartum, and infant vitamin A (100 000 IU) or placebo at 14 weeks. Milk retinol was determined at weeks 4, 14 and 26, and maternal and infant serum retinol at weeks 14 and 26. Infant retinol stores were assessed at week 26, using a modified relative dose response (MRDR) test. Among 564 women, serum retinol at 36 weeks gestation was 0·81 (sd 0·21) μmol/l, and 33·3 % were < 0·7 μmol/l. Maternal serum retinol was not different between groups, but milk retinol was higher in the vitamin A group: (0·67 v. 0·60 μmol/l; 0·52 v. 0·44 μmol/l; 0·50 v. 0·44 μmol/l at 4, 14 and 26 weeks, respectively). When expressed per gram fat, milk retinol was higher in the vitamin A group only at 4 weeks. Infant serum retinol was not different between groups. However, although most infants had deficient vitamin A stores (MRDR>0·06 %) at 26 weeks, vitamin A to infants, but not mothers, resulted in a lower proportion of infants with deficient vitamin A stores (69 v. 78 %). High-dose postpartum vitamin A supplementation failed to increase serum retinol and infant stores, despite modest effects on milk retinol. Infant supplementation, however, increased stores. There is a need for a better understanding of factors affecting absorption and metabolism of vitamin A.


1996 ◽  
Vol 126 (4) ◽  
pp. 973-983 ◽  
Author(s):  
Hans K. Biesalski ◽  
Christian Hemmes ◽  
Magdy el Hanafy ◽  
Harald Weiser ◽  
Horst Zschaebitz ◽  
...  

2007 ◽  
Vol 86 (4) ◽  
pp. 1152-1159 ◽  
Author(s):  
Birgitte R Diness ◽  
Ane B Fisker ◽  
Adam Roth ◽  
Maria Yazdanbakhsh ◽  
Erliyani Sartono ◽  
...  

Author(s):  
G Bhanuprakash Reddy ◽  
Raghu Pullakhandam ◽  
Santu Ghosh ◽  
Naveen K Boiroju ◽  
Shalini Tattari ◽  
...  

ABSTRACT Background Biochemical vitamin A deficiency (VAD) is believed to be a serious public health problem (low serum retinol prevalence &gt;20%) in Indian children, justifying universal high-dose vitamin A supplementation (VAS). Objective To evaluate in Indian children younger than 5 y the risk of biochemical VAD from the Comprehensive National Nutrition Survey, as well as dietary vitamin A inadequacy and excess over the tolerable upper limit of intake (TUL) from national and subnational surveys, factoring in fortification and VAS. Methods Child serum retinol data, corrected for inflammation, were examined to evaluate national- and state-level prevalence of VAD. Simultaneously, dietary intakes from the National Sample Survey Office and the National Nutrition Monitoring Bureau were examined for risk of dietary vitamin A deficiency against its average requirement (AR) derived for Indian children. Theoretical estimates of risk reduction with oil and milk vitamin A fortification were evaluated along with the risk of exceeding the TUL, as well as when combined with intake from VAS. Results The national prevalence of biochemical VAD measured in 9563 children was 15.7% (95% CI: 15.2%, 16.3%), and only 3 states had prevalence significantly &gt;20%. The AR of vitamin A was 198 and 191 µg/d for boys and girls; the risk of dietary inadequacy was ∼70%, which reduced to 25% with oil and milk fortification. Then, the risk of exceeding the TUL was 2% and 1% in 1- to 3-y-old and 4- to 5-y-old children, respectively, but when the VAS dose was added to this intake in a cumulative 6-mo framework, the risk of exceeding the TUL rose to 30% and 8%, respectively. Conclusion The national prevalence of VAD risk is below 20% in Indian children. Because there is risk of excess intake with food fortification and VAS, serious consideration should be given to a targeted approach in place of the universal VAS program in India.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4123-4123
Author(s):  
Alberto Rocci ◽  
Irene Ricca ◽  
Chiara Della Casa ◽  
Paolo Longoni ◽  
Mara Compagno ◽  
...  

Abstract Telomere length is considered a valuable replicative capacity predictor of human hematopoietic stem cells. Indeed, a progressive telomere shortening affects hematopoietic cells upon in vitro expansion. However, less is known on the dynamics of telomere shortening in vivo following a non-physiological replicative stress. Aim of this study was to investigate markers for cellular senescence of hematopoietic cells exposed to replicative stress induced by bone marrow reconstitution following stem cell autograft. Thus, both telomere length and in vitro functional characteristics of bone marrow (BM) and peripheral blood (PB) were evaluated at long-term in subjects who had received intensive chemotherapy and autograft. Thirty-two adults with a previous diagnosis of lymphoma were examined, at a median time of 73 months (range 42–125) since autograft. They all had received a high-dose sequential chemotherapy treatment followed by peripheral blood progenitor cell (PBPC) autograft. There were 20 male and 12 female (median age at autograft: 40 yrs., range 21–60). A Southern blot procedure using a chemiluminescence-based assay was employed to determine telomere length on samples from grafted PBPC as well as on BM and PB samples obtained at long-term during follow-up. These latter samples were also studied for their in vitro growth characteristics, assessed by short and long-term culture assays. In all cases, autograft had been performed with large quantities of hematopoietic stem cells (median autografted CD34+ve cells/kg: 9.8 x 106, range 2–24), allowing a rapid and stable hematologic reconstitution. Telomere length was found slightly shorter in BM mononuclear cells from samples taken at follow-up compared to samples from grafted material (median telomere length: 6,895 bp vs 7,073 bp, respectively; p=ns). No marked differences were observed in telomere evaluation between BM and PB cells. No significant differences were observed as well when PB telomere length of follow-up samples was compared with telomere length of PB from age-related normal subjects. BM and PB samples were then assessed for their in vitro growth characteristics. Committed and stromal progenitors were grown from all samples in good though variable quantities. However, as compared to normal controls, a statistically significant reduction of marrow-derived hematopoietic progenitors (CFU-GM - BFU-E - CFU-Mix) as well as stromal progenitors (CFU-F) was observed. Additionally, the more immature LTC-IC progenitor cell compartment was dramatically reduced, both in BM and PB samples. The results indicate that: i. the proliferative stress induced by intensive chemotherapy and post-graft hematopoietic reconstitution does not imply marked telomere loss in BM and PB cells at long-term, provided that large quantities of PBPC are used for autograft; ii. stem cells present in the graft or surviving after high-dose therapy are capable of reconstituting a sufficiently adequate hematopoiesis although the committed progenitor cell compartment and even more the immature LTC-IC progenitors are persistently reduced even at up to 10 years since autograft.


2002 ◽  
Vol 8 (3) ◽  
pp. 251-255 ◽  
Author(s):  
H. J. Kock ◽  
A. E. Handschin

Osteoporosis is a rare but potentially severe complication under high-dose, long-term unfractionated heparin therapy. Low-molecular-weight heparins (LMWHs) have gained increased importance in antithrombotic therapy over the past decade. Whether this heterogeneous group of drugs carries a comparable risk of osteoporosis in long-term application is unknown. In a standardized in vitro model, the effects of 4 different low-molecular-weight heparins (nadroparin, enoxaparin, dalteparin, certoparin) on osteoblast growth were studied at the same dose (50,μg/mL). As control, the effect of unfractionated heparin (Liquemin) was tested on human osteoblasts in vitro at an equal dose. Human osteoblast cell cultures were incubated with equal doses of the heparins, and cell concentrations were measured after 48 and 96 hours. In addition, a fluorescence assay was performed to detect potential cytotoxic effect of heparins on bone cells. In comparison to control groups of non-incubated cell cultures, LMWHs caused a significant inhibition of osteoblast growth (p<0.05). Therefore, the risk of osteoporosis under long-term therapy with high doses of LMWHs cannot be excluded and should be further evaluated in clinical trials.


1994 ◽  
Vol 30 (12) ◽  
pp. 1909-1910 ◽  
Author(s):  
A. Decensi ◽  
S. Bruno ◽  
R. Torrisi ◽  
S. Parodi ◽  
A. Polizzi

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