Retinol Concentrations Research Articles

Interactions between blood lead (Pb) concentration, oxidative stress, cellular immune response and reproductive status in livestock from a mining area

Chronic exposure to lead (Pb) in livestock grazing in abandoned mining areas affects animal welfare and productivity, as well as represents a significant food safety risk. Here, we evaluate the physiological effects of Pb exposure in goats maintained under extensive farming conditions in a non-remediated mining area. We monitored blood, fecal, and milk Pb levels in two groups of goats, pregnant (n=17) and lactating (n=24), kept in different enclosures with high soil Pb concentrations (geometric means of 270 and 143 μg/g, respectively) in Sierra Madrona mining district (Spain). We also studied the influence of Pb exposure on the ability to mount a cellular immune response, and on oxidative stress and biochemical biomarkers measured in blood. Blood Pb concentration was higher in pregnant than in lactating goats, but this difference was not observed in fecal Pb concentration. Pb levels in feces and milk concentrations were correlated with those measured in blood, with 11% of milk samples showing Pb concentrations above the maximum level (ML) for Pb in raw milk established by the EU (0.02 μg/g wet weight). Animals with increased blood Pb levels showed reduced concentrations of retinol in plasma, but these Pb levels did not affect the cellular immune response. The stimulation of the cellular immune response in lactating goats was associated with an increase in blood Pb and calcium (Ca) levels. The reproductive status and age of goats significantly affected several oxidative stress, antioxidants and plasma biochemistry variables. Goats grazing on soils contaminated by past Pb mining activities may be susceptible to detrimental health effects mediated by retinol deficiency. In view of the detected transfer of Pb through milk, special attention should be paid to the food safety of derived products (i.e. cheese).

Impact of pasture feeding cows and seasonality on the concentration of selected fat-soluble compounds in milk and their ability to be used as biomarkers of “Grass-Fed” dairy

This study investigated the impact of proportion of pasture in the cow diet on the concentration of selected fat-soluble compounds in milk including β-carotene, lutein, retinol (vitamin A), α-tocopherol (vitamin E) and zeaxanthin. Bulk tank milk samples (n = 102) were collected weekly (n = 34) across an entire lactation from three herds operating either a high (GRS), medium (PMR) or no pasture allowance (TMR) feeding system. Concentrations of β-carotene and lutein increased significantly with increasing pasture allowance, with a > 2 fold increase of β-carotene in milk, between high and no pasture allowance treatments. GRS feeding system resulted in milks with higher concentrations of retinol, α-tocopherol, and zeaxanthin, compared to both PMR and TMR systems. A biomarker model based on the fat-soluble compounds concentration in milk, demonstrated excellent differentiation of high pasture allowance derived milks from that of medium and no pasture milks, with area under the curve scores of 0.955 and 0.971 respectively. Strong correlations were observed between the concentrations of lutein and zeaxanthin in milk and the milks corresponding yellow colour, while a significant correlation was exhibited between β-carotene and b*-value. Such correlations with milk colour may have a significant impact on the consumer preference of milk and dairy products produced therefrom.

Retinol semisolid preparations in cosmetics: transcutaneous permeation mechanism and behaviour

Retinol is widely used to treat skin ageing because of its effect on cell differentiation, proliferation and apoptosis. However, its potential benefits appear to be limited by its skin permeability. Herein, we investigated the transcutaneous behavior of retinol in semisolid cosmetics, in both in vitro and in vivo experiments. In vitro experiments used the modified Franz diffusion cell combined with Raman spectroscopy. In in vivo experiments, the content of retinol in rat skin and plasma was detected with HPLC. Retinol in semisolid cosmetics was mainly concentrated in the stratum corneum in the skin of the three animal models tested, and in any case did not cross the skin barrier after a 24 h dermatologic topical treatment in Franz diffusion cells tests. Similar results were obtained in live mice and rats, where retinol did not cross the skin barrier and did not enter the blood circulation. Raman spectroscopy was used to test the penetration depth of retinol in skin, which reached 16 μm out of 34 μm in pig skin, whereas the skin of mouse and rat showed too strong bakground interference. To explore epidermal transport mechanism and intradermal residence, skin transcriptomics was performed in rats, which identified 126 genes upregulated related to retinol transport and metabolism, relevant to the search terms “retinoid metabolic process” and “transporter activity”. The identity of these upregulated genes suggests that the mechanism of retinol action is linked to epidermis, skin, tissue and epithelium development.

Determination of a Plasma Retinol Reference Interval in Eastern Collared Lizards (Crotaphytus collaris)

BackgroundThe Eastern collared lizard (Crotaphytus collaris) is a species of lizard native to the United States and Mexico and is growing in popularity in the exotic community around the world. There is minimal knowledge known on the analyte breakdown of this or closely related species. As this species becomes more popular in the exotic community more medical conditions are being identified that can be assisted in diagnosis with the establishment of ranges of the different essential analytes. Being an insectivorous lizard, this species may suffer from hypovitaminosis A. There has been a lack of antemortem diagnostics available for minimally invasive and appropriate diagnosis of this disease. Recent studies have been performed in other small insectivore species establishing plasma retinol reference intervals. Reference intervals for retinol have not been published or validated in collared lizards or any closely related species. MethodsPlasma, with a sample volume of only 50 µl, from forty clinically healthy captive bred Eastern collared lizards, twenty males and twenty females were analyzed using ultra-high-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) to determine plasma retinol concentrations. ResultsUsing UPLC-MS/MS analysis, data was normally distributed and a reference interval for plasma retinol in the Eastern collared lizard was 1.57-3.07 µg/mL (0.237-0.464 µmol/L). A mean of 0.31µg/ml; with a lower limit 95% confidence interval being 1.34-1.80 µg/ml and upper limit of 2.84-3.30 µg/ml. Vitamin A (retinol) levels were significantly different when comparing a captive bred line called Blazing Blue (n=4), with all other sampled captive bred localities. Including a closely related Aquaflames (n=16), (Sky Blue) (n=2), Western yellowhead (n=5), Fancy Spotted (n=4), Aquamarine (n=3), and Lightning Yellow (n=6); with the Blazing Blue morph being significantly lower using a t-Test comparison assuming equal variations. There was only one statistical variation seen in age groups between the 1-year-old and 6-year-old age groups with the 6-year-old age group being significantly lower than the 1-year-old age group. There was no variation based on sex. Conclusions and clinical relevanceThis study provides the first established plasma retinol range in a species in the suborder iguania. Values are valuable in assistance in diagnosing and treating hypovitaminosis A and to provide advice on dietary supplementation and dietary improvement for the collared lizards and possibly other related species as well. In addition, these values can be used to design and evaluate other studies for nutritional needs of this species. Limitations of this study include only a single season of collection, no same time comparison to liver values, some age groups were limited to only one individual, and the evaluation of only captive bred individuals.

Reduced retinol (vitamin A) and α-tocopherol (vitamin E) blood levels and increased myeloperoxidase (MPO) activity in children with high myopia

The study assessed selected parameters of redox status in the plasma of patients suffering from high myopia (HM). Thirty-five children with mean age 13.7 ± 2.7 years with HM and 40 healthy children were included. Plasma redox status parameters were determined using colorimetric kits. The levels of retinol, α-tocopherol and coenzyme Q10 were determined with a high-performance liquid chromatograph. Negative correlations were observed between the concentrations of retinol and the axial length of the eye (r = − 0.514 p < 0.001). Increased myeloperoxidase (MPO) activity (p < 0.018), and decreased concentrations of retinol (p < 0.001) and α-tocopherol (p < 0.023) in patients with HM and the axial length of the eye > 26 mm compared to controls were established. Significantly lower retinol and α-tocopherol concentrations were found in patients with the axial length of the eye > 26 mm compared to those with the axial length of the eye ≤ 26 mm (p < 0.001, p < 0.021, respectively). Increased MPO activity in advanced stages of HM may confirm an inflammatory process in HM patients. Reduced retinol and α-tocopherol concentrations and their link to disease progression indicate a need for monitoring their levels and supplementation in children with HM.

Improvement of margarine shelf-life using alginate-chitosan coated multiple W/O/W nanoemulsions containing sesamol and retinol

Alginate-chitosan (Alg-CH) coated multiple water-in-oil-in-water (W/O/W) nanoemulsion loaded with sesamol and retinol was hypothesized to enhance the oxidative stability of margarine. Total phenol content (TPC), antioxidant activity, acid value (AV), peroxide value (PV), para-anisidine value (pAV), induction period (IP), and residual values of sesamol and retinol by HPLC were determined for 90 days. Margarine with tert-butylhydroquinone (TBHQ) (T3) had the higher TPC and antioxidant activity (8.05 mg gallic acid equivalent (GAE)/g), 53.1 %) than T1 (nanoemulsion, 7.39 mg GAE/g, 38.95 %), T2 (free-sesamol and -retinol, 6.98 mg GAE/g, 31.07 %), and T4 (no antioxidant, 6.46 mg GAE/g, and 14.45 %) while T1 had higher antioxidant activity and TPC than T2 and T4 after 90 days. On day 90, the highest residual values of sesamol (200.10 mg/100 g) and retinol (118.09 μg/100 g) obtained for T1. Overall, T1 contributed to the prolonged oxidative stability of margarine, potentially offering an alternative to synthetic antioxidants.

Biochemical and Antioxidant Characteristics of Chlorococcum oleofaciens (Chlorophyceae, Chlorophyta) under Various Cultivation Conditions.

The functional state of enrichment cultures of the Chlorophycean strain Chlorococcum oleofaciens CAMU MZ-Ch4 under various cultivation conditions was studied. Experiments with different aeration conditions, cultivation durations, and nitrogen and phosphorus concentrations in the medium were carried out to evaluate the growth dynamics of the strain and its biochemical characteristics. The contents of chlorophylls, carotenoids, proteins, lipids, retinol, α-tocopherol, ascorbic acid, phenolic compounds, lipid peroxidation products, antioxidant enzymes (glutathione peroxidase, catalase, superoxide dismutase), and succinate dehydrogenase activity were measured. The lipid content on the fully supplemented Bold's basal medium increased to 381.03 mg g-1 dry weight at the late stationary growth phase. This value is 1.3-2.8 times higher than in other experiments. The use of aeration was associated with an increased content of proteins at 283.56 mg g-1 and of carotenoids at 2.12 mg g-1. Also, cultures at the early stationary growth phase with aeration showed the ability to accumulate phenolic compounds and ascorbic acid in amounts up to 0.32 mg g-1 and 0.19 mg g-1. The 74-day-old cultures had the highest contents of retinol (0.16 mg g-1) and α-tocopherol (0.68 mg g-1). Growth in nitrogen- and phosphorus-depleted media increased catalase and superoxide dismutase activity. A comprehensive analysis of all data showed that the antioxidant defence system is stress-resistant and flexible under varying aeration conditions and nitrogen and phosphorus availabilities. Thus, the strain CAMU MZ-Ch4 can be considered a potential producer of lipids, pigments, proteins, and vitamins under various culturing conditions.

Dysregulated serum concentrations of fat-soluble vitamins in dogs with chronic enteropathy.

In inflammatory bowel disease (IBD) of humans, nutrient malabsorption can result in fat-soluble vitamin deficiency, especially of vitamin D. In veterinary species, decreased concentrations of vitamin D are relatively common in dogs with chronic enteropathy (CE), but data on the status of other fat-soluble vitamins (FSVs) is lacking. Determine the serum concentrations of retinol, vitamin D, and α-tocopherol in dogs with CE compared with healthy dogs and compare clinical, clinicopathologic variables between CE and healthy dogs to detect associations with decreased FSVs concentrations. Eighteen client-owned dogs with CE and 33 healthy dogs. Serum 25-hydroxyvitamin D (25[OH]D), serum retinol and α-tocopherol concentrations were compared between groups. Correlations and multiple regression modeling were used to examine the relationship between serum 25(OH)D, retinol, and α-tocopherol concentrations and clinical and clinicopathological variables. Dogs with low serum albumin concentrations were more likely to have lower 25(OH)D concentrations than dogs with normal serum albumin concentration. Dogs with CE had higher serum concentrations of retinol, and variable α-tocopherol concentrations. The cause of these dysregulated vitamin concentrations is unclear and requires further study. Dogs with severe forms of CE should be monitored for decreased concentrations of 25(OH)D. Additional studies are needed to evaluate the clinical relevance and the possible benefit of vitamin D supplementation in these patients.

Advancing towards practice: A novel LC-MS/MS method for detecting retinol in dried blood spots

BackgroundTo date, clinical laboratories face challenges in quantifying retinol from DBS samples. Disputes arise throughout the whole detection process, encompassing the storage condition, the release strategy as well as the selection of internal standards. MethodsWe incubated DBS with ascorbic acid solution. Then, retinol-d4 in acetonitrile was introduced to incorporate isotopic internal standard and promote protein precipitation. Afterward, sodium carbonate solution was added to ionize cytochromes (such as bilirubin), which amplified the difference of their hydrophobicity to retinol. Subsequently, cold-induced phase separation could be facilitated to separate retinol from the impurities. In the end, the upper layer was injected for LC-MS/MS analysis. ResultsBy comparing the detected retinol content in whole blood and DBS samples prepared from the same volume, we confirmed the established pretreatment was capable to extract most of retinol from DBS (recovery >90 %). Thereafter, we verified that within DBS, retinol possessed satisfying stability without antioxidation. Indoor-light exposure and storage duration would not cause obvious degradation (<10 %). Following systematic validation, the established method well met the criteria outlined in the relevant guidelines. After comparing with detected DBS results to the paired plasma samples, 54 out of 60 met the acceptance limit for cross-validation of ±20 %. ConclusionsWe realized precise quantification of retinol from one 3.2 mm DBS disc. By circumventing conventional antioxidation, liquid-liquid/solid-phase extraction and organic solvent evaporation, the pretreatment could be completed within 15 min consuming only minimal amounts of low-toxicity chemicals (ascorbic acid, acetonitrile, and sodium carbonate). We expect this contribution holds the potential to significantly facilitate the evaluation of patients' vitamin A status by using DBS samples in the future.

Vitamin D Maintains Growth and Bone Mineral Density against a Background of Severe Vitamin A Deficiency and Moderate Toxicity in a Swine Model.

Excessive vitamin A (VA) negatively impacts bone. Interactions between VA and vitamin D (VD) in bone health are not well-understood. This study used a traditional two-by-two factorial design. Pigs were weaned and randomized to four treatments (n = 13/group): -A-D, -A+D, +A-D, and +A+D for 3 and 5 wk. Serum, liver, kidney, adrenal glands, spleen, and lung were analyzed by ultra-performance LC. Growth was evaluated by weight measured weekly and BMD by DXA. Weights were higher in -A+D (18.1 ± 1.0 kg) and +A+D (18.2 ± 2.3 kg) at 5 wk than in -A-D (15.5 ± 2.1 kg) and +A-D (15.8 ± 1.5 kg). Serum retinol concentrations were 0.25 ± 0.023, 0.22 ± 0.10, 0.77 ± 0.12, and 0.84 ± 0.28 µmol/L; and liver VA concentrations were 0.016 ± 0.015, 0.0065 ± 0.0035, 2.97 ± 0.43, 3.05 ± 0.68 µmol/g in -A-D, -A+D, +A-D, and +A+D, respectively. Serum 25(OH)D3 concentrations were 1.5 ± 1.11, 1.8 ± 0.43, 27.7 ± 8.91, and 23.9 ± 6.67 ng/mL in -A-D, +A-D, -A+D, +A+D, respectively, indicating a deficiency in -D and adequacy in +D. BMD was highest in +D (p < 0.001). VA and the interaction had no effect on BMD. Dietary VD influenced weight gain, BMD, and health despite VA status.

Calculation of reference intervals for the concentrations of α-tocopherol and retinol in serum using indirect data-mining procedures

BackgroundEstablishing adequate reference intervals (RIs) for vitamins A and E is essential for diagnosing and preventing deficiencies. Due to the current boom in data mining and its easy applicability, more laboratories are establishing RIs using indirect methods. Our study aims to obtain RIs using four indirect data-mining procedures (Bhattacharya, Hoffmann, Kosmic, and RefineR) for vitamins A and E. Material and methods8943 individuals were collected to establish the RIs. After using different data cleaning steps and checking whether these data should be divided according to age and gender based on multiple linear regression and variance component analyses, indirect RIs were calculated using specific Excel spreadsheets or R-packages software. ResultsA total of 2004 records were eligible. For vitamin A, the RIs obtained were (1.11 − 2.68) µmol/L, (1.13 − 2.70) µmol/L, (1.13 − 2.71) µmol/L, and (1.17 − 2.66) µmol/L using the Bhattacharya, Hoffmann, Kosmic and RefineR approaches, respectively. For vitamin E, these intervals were (17.3 − 49.9) µmol/L (Bhattacharya), (17.3 − 48.9) µmol/L (Hoffmann), (19.6 − 50.3) µmol/L (Kosmic), and (19.4 − 50.9) µmol/L (RefineR). In all cases, the RIs were comparable. ConclusionsSuitable RIs for vitamins A and E were calculated using four indirect methods that are suitable and adapted to our population’s demographic characteristics.

α-Tocopherol and retinol content in Holder pasteurized versus high-pressure processed human milk during 6 months of storage

Human milk is a vital source of nutrition for infants providing essential nutrients for optimal growth and development. However, the processing methods applied to ensure its safety may affect its nutritional composition. The aim of this study was to compare the nutritional profile of α-tocopherol and retinol content in human milk, both raw and processed by Holder pasteurization or high-pressure processing. Our study followed a design that included milk samples obtained from 12 female donors (age ranged from 30 to 38) in the lactation period up to 6 months after delivery. Every milk sample was divided into four groups: (i) no treatment, (ii) subjected to Holder pasteurization (HP), (iii) and (iv) subjected to high-pressure processing (HPP), which differed in the way the pressure was applied. The results showed that both HP and HPP significantly affected the nutritional profile of the milk. Retinol level was approximately 20 % lower after both treatments than in untreated milk. The main difference was in tocopherol levels, which decreased by 46 % after HP, whereas these concentrations decreased by only 26 % in the cumulative pressure HPP-treated samples. These results suggest that the use of HPP should be considered as a prospective approach to human milk processing. Since HPP has advantages in preserving heat-sensitive compounds and the levels of vitamin E decrease less.

VITAMINS A AND E CONTENT IN THE TISSUES OF THE BANK VOLE (MYODES (CLETHRIONOMYS) GLAREOLUS) AND COMMON SHREW (SOREX ARANEUS) INHABITING IN KARELIA

We studied the vitamins A (retinol) and E (α-tocopherol) content in the tissues of the bank vole (Myodes (Clethrionomys) glareolus) and common shrew (Sorex araneus) inhabiting the northern periphery of its range. The distribution of vitamin A in the common shrew and bank vole tissues was similar, the highest content was found in the liver, and the lowest level was in the heart. Agerelated differences in retinol content were detected in the kidneys of two species, as well as in the skeletal muscle of the shrew. Significantly lower vitamin E content was found in all organs of young shrews before wintering, compared to adult wintered animals, while in the bank vole no such age-related differences were found. Interspecies differences in the levels of vitamins A and E in the liver of overwintered animals were revealed. The results obtained show that vitamins A and E content in the tissues of the bank vole and the common shrew is determined by the metabolic processes and the ecological characteristics of the species. The vitamins level in the common shrew depends largely on age.

Pro-inflammatory diets are associated with higher C-reactive protein and lower plasma concentrations of vitamins with anti-inflammatory potential, in the EPIC-Norfolk cohort

The development of multiple long-term conditions (MLTC) has been shown to be associated with low-grade chronic inflammation(1). The Dietary Inflammatory Index (DII®) is a literature-based dietary score that was developed to measure the potential impact of diet on the inflammatory status of an individual(2). In this study, we aimed to validate the DII® score against biomarkers, including high- sensitivity C-reactive protein (hs-CRP), and plasma concentrations of vitamin C, retinol and α- tocopherol in European Prospective Investigation Into Cancer and Nutrition (EPIC)-Norfolk participants, aged 39–79 years at baseline(3).The DII® score was calculated using a 130-item Food Frequency Questionnaire collected at baseline, between 1993 and 1997. The dietary intakes were adjusted to a 2000 kcal/day diet, to assess diet quality independently of diet quantity. Non-fasting serum cholesterol, hs-CRP, and plasma α- tocopherol, vitamin C and retinol concentrations were also measured at this time-point. Data collected via a self-administered Health and Lifestyle Questionnaire were used to establish classification of a number of variables. Analyses were conducted on sub-samples with a DII® score and measures of hs-CRP (8,034 men and 9,861 women), and concentrations of vitamin C (9,866 men and 11,702 women), retinol (3,673 men and 3,517 women) and cholesterol-adjusted α- tocopherol (3,623 men and 3,476 women). Analysis of covariance and linear regression were used to study associations across sex-specific quintiles of the DII® score (adjusted for age, BMI, smoking status, physical activity, social class and educational level), where a higher score indicates a more pro-inflammatory diet.Mean concentrations in men and women were 2.99 and 3.09 mg/L for hs-crp, 47 and 59 μmol/L for vitamin C, 53 and 50 μg/dL for retinol and 4.34 and 4.42 μmol/mmol for cholesterol-adjusted α- tocopherol, respectively. In both men and women, mean hs-CRP was higher if the diet was more pro-inflammatory (p-trend = 0.02 in men and 0.07 in women), while concentrations of vitamin C, retinol and α-tocopherol were significantly lower (p-trend &lt; 0.001). Positive associations for hs-CRP, but negative associations for plasma concentrations of vitamin C, retinol and α-tocopherol were evident in both men and women, after adjustments for covariates (p-trend &lt; 0.001). The differences between Q1 and Q5 adjusted means for hs-CRP, vitamin C, retinol and α-tocopherol were +9.4%, -22.1%, -3.9% and -8.6% in men and +7.9%, -17.5%, -4.8% and -7.6% in women, respectively.We observed statistically significant positive associations between the DII® score and hs-CRP, a well-known inflammatory biomarker, whilst significant negative associations were found for circulating concentrations of three anti-inflammatory vitamins, after adjustment for covariates. These findings indicate that the DII® score is a valid measure of the inflammatory potential of diet in these middle-aged and old adults, making it possible to study the inflammatory role of diet in MLTC development.

Adipocyte HSL is required for maintaining circulating vitamin A and RBP4 levels during fasting

Vitamin A (retinol) is distributed via the blood bound to its specific carrier protein, retinol-binding protein 4 (RBP4). Retinol-loaded RBP4 is secreted into the circulation exclusively from hepatocytes, thereby mobilizing hepatic retinoid stores that represent the major vitamin A reserves in the body. The relevance of extrahepatic retinoid stores for circulating retinol and RBP4 levels that are usually kept within narrow physiological limits is unknown. Here, we show that fasting affects retinoid mobilization in a tissue-specific manner, and that hormone-sensitive lipase (HSL) in adipose tissue is required to maintain serum concentrations of retinol and RBP4 during fasting in mice. We found that extracellular retinol-free apo-RBP4 induces retinol release by adipocytes in an HSL-dependent manner. Consistently, global or adipocyte-specific HSL deficiency leads to an accumulation of retinoids in adipose tissue and a drop of serum retinol and RBP4 during fasting, which affects retinoid-responsive gene expression in eye and kidney and lowers renal retinoid content. These findings establish a novel crosstalk between liver and adipose tissue retinoid stores for the maintenance of systemic vitamin A homeostasis during fasting.

O07 Lower doses of retinol facilitate cell proliferation and epidermal thickening in photoaged skin

Abstract Introduction and aims Chronic exposure to solar ultraviolet radiation leads to cutaneous hypertrophic photoageing which clinically manifests as wrinkles, skin laxity and hyperpigmentation. This photoaged phenotype is underscored by a remodelled cutaneous microenvironment including epidermal thinning and rete ridge flattening. We have previously shown that cosmeceutical formulations of 0.3% and 1% retinol can effectively induce epidermal thickening and keratinocyte proliferation. However, these concentrations require careful usage to limit potential irritancy issues, highlighting a need to explore the benefits of lower dose retinol for daily skincare. Therefore, we compare the efficacy of lower doses of retinol in facilitating epidermal thickness and proliferation in photoaged skin, as this currently remains unknown. Methods Using the in vivo Manchester Patch Test Assay, test substances (vehicle and retinol at concentrations of 0.025%, 0.05%, 0.1% and 1%) were applied under occlusion to extensor forearms of healthy but photoaged volunteers (three men, three women; age range 66–86 years) for 12 days. Resultant skin biopsies were processed for histological assessment of epidermal thickness and keratinocyte proliferation. Results Epidermal thickness was significantly increased with 0.025% (P &amp;lt; 0.05), 0.05%, 0.1% and 1% (all P &amp;lt; 0.01) retinol treatment, compared with baseline or vehicle. Immunofluorescence staining of the proliferation marker Ki67 identified elevated keratinocyte proliferation following retinol treatment (P &amp;lt; 0.05 for 0.025%, 0.05% and 1%) compared with baseline. Although Ki67 expression in the 0.1% retinol treatment was elevated, significance was not achieved compared with baseline. However, compared with the vehicle, all retinol concentrations significantly increased Ki67 expression (P &amp;lt; 0.05). Clinically, 50% of volunteers showed an erythemal irritancy response to 1% retinol only. Conclusions We established that lower doses of retinol are capable of inducing keratinocyte proliferation and epidermal thickening without irritancy issues. Therefore, long-term effective treatment of photoaged skin with low-dose retinol products may be the preferred choice for individuals where retinol sensitivity has previously been an issue.

PSIII-10 Impact of late gestation vitamin A and D injection on offspring growth and immune parameters in piglets

Abstract Supranutritional use of vitamins may have an impact on mortality rates of sows and piglets. Specifically, injection of vitamin A, and vitamin A and D (VitAD) has improved subsequent preweaning mortality when given to sows after weaning and improved immune response in offspring when administered to cattle in late gestation. However, little work has been conducted to investigate developmental impacts of gestational vitamin supplementation in piglets that may impact immune development. To investigate the relationship of VitAD supplementation on offspring development, this study evaluated sows (n = 20) injected intramuscularly with VitAD (312,000 IU vitamin A, 52,500 IU vitamin D) or a saline at d 85 of gestation. Effect of VitAD on performance and immune development was assessed from birth through wk 5 post weaning. Starting at birth (n = 95 VitAD, n = 114 control) piglet serum was collected weekly during the 4 wk lactation period, and a subset of piglets were bled weekly through the nursery. Blood was analyzed for retinol concentrations from birth through 5 wk post weaning and immune parameters via complete blood count analysis for 5 wk post weaning. Milk samples were also collected weekly during lactation and assessed for retinol concentrations via liquid chromatography. Data were assessed via a mixed procedure (SAS 9.4) with sow as random and treatment as fixed variables. Covariate of wean age was assessed for post weaning growth and of sampling time for retinol and CBC analysis. At farrowing, differences in birth weights were not observed (P ≥ 0.69). Through the lactation phase, control piglets had a tendency for increased average daily gain (P ≥ 0.07); however, no differences (P ≥ 0.27) were observed in piglet growth performance during the nursery phase. Blood and immune parameters assessed were not different across treatments from birth through 9 wk of age. Circulating retinol concentrations were greater in the control group, (P ≤ 0.05) at 15, 22, and 28 d of age, compared with VitAD. Milk retinol concentrations were increased in the VitAD group on d 8 of life, (P ≤ 0.05), but not at any other time during lactation. These results suggest that supplementation of VitAD on d 85 of gestation in sows impacts the retinol concentrations in milk for a limited period, but not growth or circulating retinol and immune parameters in piglets at any age. Based on these data, efficacy of supranutritional injection of VitAD may be timing specific and limited to benefiting the litter during lactation. Further research is needed to assess specificity of timing and impacts on piglet health and survival.

Early postnatal high-dose fat-soluble enteral vitamin A supplementation for moderate or severe bronchopulmonary dysplasia or death in extremely low birthweight infants (NeoVitaA): a multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial

Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation. This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32+0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24. Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups. Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations. Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).

Role of antioxidants as immunity booster in obesity and diabetes: a systematic review on neuro-gliopathies perspective

Background: The main objective of the study was to carry out a systematic literature review to investigate the beneficial role of antioxidants in obesity and diabetes and the association of antioxidants in neuro-gliopathies and gut microbiome on antioxidant production and enteric nervous system (ENS) protection. Methods: A literature search was done electronically on 8 June 2022 in the databases Google Scholar, and PubMed, reviewing all the articles published in English. There were no limitations for the study (region, or any time frame). The study included randomized controlled trials (RCTs) and observational studies on a human subject, primarily focusing on information such as a change in body weight, body mass index (BMI), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), fasting blood glucose level, glycated haemoglobin (HbA1c), and other parameters that connected with diabetes and obesity. The search was also conducted for neuro-gliopathies and gut microbiome. Results: The beginning database search picked out a total of 2,428 articles, 1,310 in PubMed, 876 in Google Scholar, and 242 records from other sources. A total of 2,040 (total duplicates 388) was found after removing the duplicated articles, and after reading the title and abstracts were further decreased to 139 full-text articles. These 139 studies went for full-text analysis, which resulted in the exclusion of 123 studies and generated a final 16 articles included for systemic analysis. Discussion: This literature search of present studies shows the interconnection between antioxidant intake among obese and diabetes neuro-gliopathies. The findings indicate both obese and diabetic patients have a minimum content of antioxidants, especially carotenoids, retinol, ascorbic acid, tocopherol, magnesium, and zinc. While few research illustrated that ingestion of the abovementioned antioxidants was lowered among diabetes and obese subjects in contrast with their normal-weight population, this was not endorsed by every study.

Silica Microparticles from Sugarcane By-Products as an Encapsulation System for Retinoids Aimed at Topical Sustained Release.

The encapsulation of retinol within silica microparticles has emerged as a promising opportunity in the realm of cosmetic and pharmaceutical formulations, driven by the need to reinforce the photoprotection and oxidation stability of retinol. This work examines the process of encapsulating retinol into silica microparticles. The association efficiency, microparticle size, molecular structure, morphology, oxidation, and release profile, as well as biocompatibility and skin sensitization, were evaluated. Results showed that 0.03% of retinol and 9% of emulsifier leads to an association efficiency higher than 99% and a particle size with an average of 5.2 µm. FTIR results indicate that there is an association of retinol with the silica microparticles, and some may be on the surface. Microscopy indicates that when association happens, there is less aggregation of the particles. Oxidation occurs in two different phases, the first related to the retinol on the surface and the second to the associated retinol. In addition, a burst release of up to 3 h (30% free retinol, 17% associated retinol) was observed, as well as a sustained release of 44% of retinol up to 24 h. Encapsulation allowed an increase in the minimal skin cytotoxic concentrations of retinol from 0.04 μg/mL to 1.25 mg/mL without skin sensitization. Overall, retinol is protected when associated with silica microparticles, being safe to use in cosmetics and dermatology.