Pancreatic lipase-related protein 2 is responsible for the increased hepatic retinyl ester hydrolase activity in vitamin A-deficient mice.

The formation and hydrolysis of hepatic retinyl esters (RE) is a key process in maintaining serum retinol homeostasis. During vitamin A deficiency, the activity of RE hydrolases (REH) in liver increases to cope with the reduced dietary vitamin A intake. However, it remains unclear which REH is the main enzyme responsible for RE hydrolysis in the liver under physiological conditions. Our previous studies have shown that pancreatic lipase-related protein 2 (PLRP2) is conditionally expressed in the liver and may be involved in the hydrolysis of hepatic RE. In the current study, we generated Plrp2-/- mice using transcription activator-like effector nuclease technology to investigate the role of PLRP2 in the metabolism of hepatic RE. Compared with the mice fed normal diet, the hepatic REH activity of wild-type (WT) mice fed vitamin A-deficient diet (VAD) increased significantly, while this activity did not increase in Plrp2-/- mice fed VAD. Plrp2-/- mice showed higher residual RE content in liver and lower serum retinol level, compared with WT mice fed VAD. Hepatic metabolic profiling from 1 H NMR-based metabolomics suggested that Plrp2-/- mice were more sensitive to VAD. Docking analysis and enzyme activity assay revealed that retinyl palmitate was the substrate with higher affinity for PLRP2. Our results indicate that Plrp2 can be activated in the liver and is responsible for the increased REH activity in the liver of mice fed VAD.

The Effects of an Oil and Wheat Flour Fortification Program on Pre-School Children and Women of Reproductive Age Living in Côte d'Ivoire, a Malaria-Endemic Area.

Anemia and micronutrient deficiencies are widespread in sub-Saharan Africa, but the impact of food fortification is still debated. The objective of this study was to estimate the iron and vitamin A status of preschool children (PSC) and women of reproductive age (WRA) in households consuming fortified oil and wheat flour. The survey was cross-sectional in a rural and an urban area. Data on demographics, socioeconomic status, and fortified foods were collected at households. Hemoglobin (Hb), retinol binding protein (RBP), ferritin, soluble transferrin receptors (sTfR), subclinical inflammation, and Plasmodium spp. infection data were collected. In PSC, vitamin A deficiency (VAD) was prevalent, but for each 1 mg retinol equivalents (RE)/kg of oil consumed, RBP increased by 0.37 µmol/L (p = 0.03). In WRA, there was no significant VAD in the population (0.7%). Anemia was found in 92.2% of rural and 56.3% of urban PSC (p < 0.001). PSC with access to adequately fortified flour had Hb concentrations 15.7 g/L higher than those who did not (p < 0.001). Hb levels increased by +0.238 g/L per mg/kg increase in iron fortification levels (p < 0.001). The national program fortifying vegetable oil with vitamin A and wheat flour with iron and folic acid may have contributed to improved micronutrient status of PSC from two areas in Côte d'Ivoire.

Giardiasis as a predictor of childhood malnutrition in Orang Asli children in Malaysia.

A cross-sectional study to examine the association of giardiasis with protein-energy malnutrition, vitamin A deficiency and iron deficiency anaemia was conducted among Orang Asli children in Selangor, Malaysia. A total of 281 children aged 2-15 years were studied. The data were collected using structured questionnaires, anthropometric measurements and laboratory analysis of blood and faecal samples. The results showed that 24.9% of the children were infected with Giardia duodenalis, while 56.5, 61.3 and 15.1% had significant underweight, stunting and wasting, respectively. Giardiasis was statistically identified as a strong predictor of significant wasting in this study population.

In-vitro uptake of vitamin A by Plasmodium falciparum.

The vitamin-A uptake of Plasmodium falciparum was investigated by culturing a standard isolate of the parasite (FCR-3) with (3)H-labelled vitamin A, at concentrations of the vitamin corresponding to those normally present in human serum. The (3)H-labelled vitamin A accumulated in the parasites from each culture in a parasitaemia-dependent manner. The radioactivity detected in the parasites increased with parasite maturation from the ring to the late-trophozoite stage. In addition, most of the radioactivity incorporated into the parasite cells was in the cytoplasm. The accumulation of vitamin A in the cytoplasm of late trophozoites indicates that P. falciparum may use vitamin A, from its human host, as an antioxidant, to protect itself from oxidative stress while intra-erythrocytic. The amount of the vitamin taken up by the parasite in vitro is small compared with the deficit that sometimes causes severe hypovitaminosis A in malaria cases. Consumption of vitamin A by the parasites together with the systemic decreases in non-enzymatic antioxidants that are seen in malaria may together cause this characteristic hypovitaminosis.

Haemoconcentration associated with low vitamin A status can mask anaemia.

As part of a pig study to elucidate the interactions between low vitamin A status and helminth infections, surprisingly, we observed higher haemoglobin levels and packed cell volumes in the pigs with low vitamin A status. A possible haemoconcentration effect, due to some disturbance in the regulation of the extracellular fluid volume, could lead to underestimation of the prevalence of anaemia in vitamin A deficient human populations. Therefore, this phenomenon needs to be further clarified in studies involving determination of plasma volumes.

Marginal vitamin A deficiency in pigs experimentally infected with Trichuris suis: a model for vitamin A inadequacy in children.

The development of an experimental model for marginal vitamin A deficiency in humans is of major interest, enabling the elucidation of possible interactions with helminth infections. We established a useful experimental model for human vitamin A deficiency in young pigs; deficiency was induced through a depletion method encompassing both sow and offspring. We report on a 2 x 2 study in which 18-week-old vitamin A deficient pigs and vitamin A sufficient littermates were infected with both of the intestinal nematodes Trichuris suis and Ascaris suum and followed for 14 weeks through 32 weeks of age. Forty-nine pigs were followed with respect to bodyweight, liver biopsies and blood samples for retinol concentration and faecal samples for parasite eggs and worms. Liver and serum concentrations of vitamin A were significantly diminished in the vitamin A deficient (VAD) group as compared to the vitamin A sufficient (VAS) group both before (P < 0.001) and after inoculation with T. suis and A. suum (P < 0.02). A significant correlation between retinol content in micro-biopsy needle samples and gross liver content was found (r = 0.457, n = 48, P = 0.001). The adult T. suis worms in the VAD group were marginally smaller (36.7 vs 40.2 mm; P = 0.08), more orally located (section 2.9 vs 3.9; P = 0.08) and had a higher proportion of males (0.58 vs 0.50; P = 0.08) whereas there were no effects of diet treatment on fecundity. The proportion of pigs with faecal T. suis egg excretion 12 weeks post inoculation (p.i.) was significantly lower in the VAD group compared with the VAS infected group (21 vs 78%; P = 0.036). In addition, faecal T. suis egg excretion was significantly lower in the VAD group at both week 11 (P = 0.040) and week 12 p.i. (P = 0.021). Vitamin A deficiency may have altered the functional integrity of the mucosal intestinal epithelium, disrupting the normally delicate attachment of T. suis and leading to the premature termination of infection. However, a possible antagonistic interaction, if verified, should not preclude interventions to improve vitamin A status, i.e., treatment should accompany anthelmintic treatment.

Five-year follow-up of a food-based vitamin A intervention in Tanzania.

OBJECTIVE: : To evaluate the long-term effects of a horticultural and nutrition education intervention in rural Tanzania. DESIGN: : A quasi-experimental post-test design was used. SETTING: : The research was carried out in 10 villages in Singida region, Tanzania. SUBJECTS: : Mothers and their children aged 6-71 months (n = 236) from an experimental (Ilongero) and control (Ihanja) area were interviewed regarding knowledge and practices related to vitamin A nutrition. Intake of vitamin A-rich foods by the children during the 7 days prior to the interview was recorded. Stools were examined for helminths and serum samples were analysed for retinol and C-reactive protein (CRP) (n = 146) for the children aged 12-71 months. RESULTS: : Knowledge and practices were more favourable to vitamin A intake in the experimental area than in the control area, and an increased frequency of intake of green leaves was associated with higher serum retinol values. The experimental area had lower mean serum retinol levels (13.7 microg dl(-1), n = 75) than the control area (19.3 microg dl(-1), n = 71). One likely confounder was the higher helminth infestation in the experimental area (n = 75, 79%) than in the control area (n = 71, 49%) (P < 0.001). Children with helminths (n = 94) had a lower mean serum retinol level than those without (n = 52) (12.3 +/- 5 vs. 24 +/- 10 microg dl(-1); P = 0.001). CONCLUSIONS: : Food-based vitamin A programmes can make sustainable improvements in knowledge and dietary practices but these may not necessarily be reflected in increases in serum retinol. Programme implementation and evaluation should take confounders into consideration as, in this case, helminth infestation.

Effects of a diet deficient in vitamins A, D, and E on infectivity, growth, and development of Echinostoma trivolvis in domestic chicks.

The effects of a diet deficient in fat-soluble vitamins on infectivity, growth, and development of Echinostoma trivolvis in domestic chicks were studied. The vitamin-deficient diet (experimental) contained 21% protein, but lacked vitamins A, D, and E. The control diet was isocaloric, contained more than 18% protein, and a normal vitamin complement. There were no significant differences in chick infectivity or worm recovery at 7, 10, or 14 days postinfection (p.i.) from hosts on either diet. Likewise, there were no significant differences in chick weights at 7, 10, or 14 days p.i. in hosts maintained on either diet. However, worm weights and body and organ dimensions were significantly greater at 10 and 14 days p.i. in worms from control versus experimental hosts; worms from experimental hosts never became ovigerous. Our results support Beaver's speculation that E. trivolvis develop poorly in avian hosts lacking fat-soluble vitamins.

Retinol deficiency and Dipetalonema viteae infection in the hamster.

Following chronic retinol (vitamin A) deprivation leading to exhaustion of liver vitamin A reserves below 50 I.U. per liver hamsters were fed diets either deficient in ("Rd":250 I.U.A./kg in experiment I, 1000 I.U.A/kg in experiment II) or enriched with retinol ("Rw":10000 I.U.A/kg in experiment I and II). After 4 weeks some of the animals (36 in experiment I, 30 in II) were infected with 150 3rd-stage larvae of D. viteae, while clean animals were kept as controls. The retinol status, the immune response (indirect fluorescent antibody test: IFAT) and parasitological parameters were examined up to 8 (experiment I) and 12 weeks (experiment II) post infection (p.i.). Rd hamsters had levelling off of weight gain or weight loss, severely deficient retinol levels in serum and liver, and high mortality. Weight gain was less in infected than in uninfected hamsters, and the capacity of infected Rw animals to restore liver retinol was significantly lower than that of uninfected Rw animals. IFAT titres were similar in Rd and in Rw animals, but microfilaraemia was significantly enhanced at 8 and 10.5 weeks p.i. in Rd hamsters. While the number of worms recovered from Rd and Rw hamsters was similar, there was a significant increase in the ratio of female to male worms in Rd hamsters. Rd hamsters in experiment I produced 3.3 times the worm mass per 100 g body-weight than Rw hamsters. Also, the average mass per female worm was significantly higher in Rd than Rw in hamsters, and this parameter was negatively correlated with the liver retinol concentration in experiment I(r = -0.89). Retinol deficiency has a marked effect on growth and fertility of D. viteae in hamsters.

Vitamin A absorption in ascariasis.

Vitamin A absorption was studied in a group of 28 adult patients with ascariasis and 12 healthy adult controls, using a simplified vitamin A absorption test. In over 70% of the patients with ascariasis malabsorption of vitamin A was demonstrated. Stool egg counts for ascaris were not related to the degree of vitamin A malabsorption. Of the 23 patients in whom a D-xylose absorption test was performed, seven showed excretion less than 20% in 5 hr. Immediately after expulsion of the worms, vitamin A absorption improved in 13 out of 14 patients tested (in nine to normal level). The results of this study suggest that ascariasis in populations on marginal intakes of vitamin A and its precursors is an important contributing factor in producing clinical vitamin A deficiency.