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Retinol isotope dilution accurately predicts liver reserves in piglets but overestimates reserves in lactating sows.

ABSTRACT: IMPACT STATEMENT:Vitamin A (VA) deficiency and hypervitaminosis A have been reported in groups of people worldwide. Conventional biomarkers of VA deficiency (e.g. serum retinol concentration, dose response tests) are not able to distinguish between sufficiency and hypervitaminosis A. Retinol isotope dilution (RID) predictions of VA status have been validated in humans and animal models from deficiency through toxicity; however, RID during life stages with unique issues related to isotopic tracing, such as infancy and lactation, requires further evaluation. This study investigated RID in piglets and lactating sows as models for human infants and women. In piglets, RID successfully determined VA deficiency (confirmed with liver analysis), and that the tracer mixes quickly. Conversely, in lactating sows, although serum and milk enrichments were similar, traditional RID equations overestimated VA stores, likely due to losses of tracer and higher extrahepatic VA storage than predictions. These data inform researchers about the challenges of using RID during lactation.

SUBMITTER: Sheftel J

PROVIDER: S-EPMC6545696 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Retinol isotope dilution accurately predicts liver reserves in piglets but overestimates reserves in lactating sows.

Sheftel Jesse J Surles Rebecca L RL Tanumihardjo Sherry A SA

Experimental biology and medicine (Maywood, N.J.) 20190319 7

<h4>Impact statement</h4>Vitamin A (VA) deficiency and hypervitaminosis A have been reported in groups of people worldwide. Conventional biomarkers of VA deficiency (e.g. serum retinol concentration, dose response tests) are not able to distinguish between sufficiency and hypervitaminosis A. Retinol isotope dilution (RID) predictions of VA status have been validated in humans and animal models from deficiency through toxicity; however, RID during life stages with unique issues related to isotopi ...[more]

PMID: 30889962

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Project description:Background:Retinol isotope dilution (RID) indirectly estimates vitamin A (VA) status. Multicompartment modeling of RID data is used to refine study designs and equations to calculate VA stores. Previous studies suggest that VA in slowly turning over pools is not traced if follow-up is not long enough; however, shorter RID studies are being investigated. Few long-term models have been published. Objective:We determined the effect of time on mathematical models of VA kinetics, model parameters, and outcomes. Methods:In this longitudinal study, women (mean ± SD age: 22 ± 3 y; n = 7) were given 2.0 µmol [14,15]-13C2-retinyl acetate. Blood samples were staggered from 4 h to 152 d; the fraction of dose in serum was modeled with compartmental models. Four model-time categories were created: full models that used all data (median: 137 d; range 97-152 d) and truncated shorter studies of 14, 27, and 52 d (range: 42-62 d). Outcomes included number of compartments to adequately model serum data, kinetic parameters, total traced VA mass, and time-to-dose equilibration. To gain insight into longer follow-up, an additional participant was given 17.5 µmol 13C4-VA, and data were modeled as long as enrichment was above baseline (5 y). Results:Longer follow-up times affected kinetic parameters and outcomes. Compared with the 14-d models, long-term full models required an additional compartment for adequate fit (14.3% compared with 100%; P = 0.0056) and had longer [median (quartile 1, quartile 3)] whole-body half-life [15.0 d (10.5, 72.6 d) compared with 135 d (115, 199 d); P = 0.0006], time-to-dose equilibration [3.40 d (3.14, 6.75 d) compared with 18.9 d (11.2, 25.7 d); P < 0.0001], and total traced mass [166 µmol VA (162, 252 µmol VA) compared with 476 µmol VA (290, 752 µmol VA); P = 0.0031]. Conclusions:Extended RID sampling alters numerous mathematically modeled, time-dependent outcomes in women. Length of study should be considered when using mathematical models for calculating total-body VA stores or kinetic parameters related to VA turnover. This study is registered at www.clinicaltrials.gov as NCT03248700.

Project description:BackgroundLactose synthesis rate is an important factor in milk production and quality in mammals. Understanding the lactose synthesis mechanism is crucial for the improvement of milk quantity and quality. However, research on the temporal gene changes regarding lactose synthesis during the whole lactation is still limited. The objective of this study was to determine gene expression profiles related to lactose synthesis in sows during lactation, and further identify the critical steps or key factors in the lactose synthesis pathway.MethodsTo determine the temporal change of factors related to lactose synthesis in sows, milk from eight multiparous Yorkshire sows (parity 3 to 6) was collected at 0 h, 2 h, 6 h, 12 h, 24 h, day 2, 3, 4, 7, 14, and 21 after birth of the first piglet. Lactose content, prolactin and progesterone concentration, and gene or protein expression related to lactose synthesis were measured.ResultsThe lactose yield increased gradually from D2 to D21 and reached a maximum at D14 (3-fold from D2) during lactation (P < 0.05). A similar trend was observed in IGF-1 and insulin concentrations in milk, both of which were greatest at D3 with a subsequent decrease during middle to late lactation. Conversely, milk prolactin and progesterone concentrations moderately decreased with the progression of lactation. The mRNA or protein expressions related to glucose transportation (GLUT1), glucose-galactose interconversion (HK1 and UGP2), UDP-galactose transportation (SLC35A2), and lactose synthetase (LALBA and B4GALT1) in the lactose synthesis pathway were significantly upregulated during early to middle lactation and plateaued by late lactation (P < 0.05).ConclusionsThese novel findings suggest that the increased lactose synthesis in lactation was related to the coordinated upregulation of genes or enzymes in the lactose synthesis pathway, and glucose transportation (GLUT1) and lactose synthetase (LALBA and B4GALT1) might be the critical steps in the lactose synthesis pathway of sows during lactation.

Project description:Senecavirus A (SVA) is a picornavirus that causes acute vesicular disease (VD), that is clinically indistinguishable from foot-and-mouth disease (FMD), in pigs. Notably, SVA RNA has been detected in lymphoid tissues of infected animals several weeks following resolution of the clinical disease, suggesting that the virus may persist in select host tissues. Here, we investigated the occurrence of persistent SVA infection and the contribution of stressors (transportation, immunosuppression, or parturition) to acute disease and recrudescence from persistent SVA infection. Our results show that transportation stress leads to a slight increase in disease severity following infection. During persistence, transportation, immunosuppression, and parturition stressors did not lead to overt/recrudescent clinical disease, but intermittent viremia and virus shedding were detected up to day 60 postinfection (p.i.) in all treatment groups following stress stimulation. Notably, real-time PCR and in situ hybridization (ISH) assays confirmed that the tonsil harbors SVA RNA during the persistent phase of infection. Immunofluorescence assays (IFA) specific for double-stranded RNA (dsRNA) demonstrated the presence of double-stranded viral RNA in tonsillar cells. Most importantly, infectious SVA was isolated from the tonsil of two animals on day 60?p.i., confirming the occurrence of carrier animals following SVA infection. These findings were supported by the fact that contact piglets (11/44) born to persistently infected sows were infected by SVA, demonstrating successful transmission of the virus from carrier sows to contact piglets. Results here confirm the establishment of persistent infection by SVA and demonstrate successful transmission of the virus from persistently infected animals.IMPORTANCE Persistent viral infections have significant implications for disease control strategies. Previous studies demonstrated the persistence of SVA RNA in the tonsil of experimentally or naturally infected animals long after resolution of the clinical disease. Here, we showed that SVA establishes persistent infection in SVA-infected animals, with the tonsil serving as one of the sites of virus persistence. Importantly, persistently infected carrier animals shedding SVA in oral and nasal secretions or feces can serve as sources of infection to other susceptible animals, as evidenced by successful transmission of SVA from persistently infected sows to contact piglets. These findings unveil an important aspect of SVA infection biology, suggesting that persistently infected pigs may function as reservoirs for SVA.

Dataset Information

Retinol isotope dilution accurately predicts liver reserves in piglets but overestimates reserves in lactating sows.

Publications

Retinol isotope dilution accurately predicts liver reserves in piglets but overestimates reserves in lactating sows.

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