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Background There is scant information on the breastmilk vitamin A (BMVA) concentration of lactating women in developing countries, partly due to lack of methods applicable in-field. Objective To assess BMVA concentrations of samples collected from lactating women of children aged 6-23 months, in Mecha district, Ethiopia. Subjects/methods Data on socio-demographic and anthropometric characteristics were collected from randomly selected lactating women (n = 104). Breast milk samples were collected and vitamin A concentrations were analyzed using HPLC and iCheck FLUORO then the two measurements were compared. Results The prevalence of underweight (BMI < 18.5 kg/m(2)) among lactating women was 17%. Seventy six percent of the BMVA values were < 1.05 mu mol/l and 81% were < 8 mu g/g fat. The mean BMVA concentration accounted to 41% of the estimated average value for mothers in developing countries. The BMVA values from HPLC and iCheck were correlated (r = 0.59, p = < 0.001), but it was not strong. Conclusions The result indicates the low vitamin A status of the lactating women and their children. It further indicates that intake assessments should not use average BMVA composition. The possibility of using iCheck for monitoring interventions designed to improve vitamin A status of lactating women with low BMVA requires further investigation.
In sub-Saharan Africa, infectious diseases and malnutrition constitute the main health problems in children, while adolescents and adults are increasingly facing cardio-metabolic conditions. Among adolescents as the largest population group in this region, we investigated the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors (CRFs), and evaluated demographic, socio-economic and medical risk factors for these entities. In a cross-sectional study among 188 adolescents in rural Ghana, malarial infection, common infectious diseases and Body Mass Index were assessed. We measured ferritin, C-reactive protein, retinol, fasting glucose and blood pressure. Socio-demographic data were documented. We analyzed the proportions (95% confidence interval, CI) and the cooccurrence of infectious diseases (malaria, other common diseases), malnutrition (underweight, stunting, iron deficiency, vitamin A deficiency [VAD]), and CRFs (overweight, obesity, impaired fasting glucose, hypertension). In logistic regression, odds ratios (OR) and 95% CIs were calculated for the associations with socio-demographic factors. In this Ghanaian population (age range, 14.4-15.5 years; males, 50%), the proportions were for infectious diseases 45% (95% CI: 38-52%), for malnutrition 50% (43-57%) and for CRFs 16% (11- 21%). Infectious diseases and malnutrition frequently co-existed (28%; 21-34%). Specifically, VAD increased the odds of non-malarial infectious diseases 3-fold (95% CI: 1.03, 10.19). Overlap of CRFs with infectious diseases (6%; 2-9%) or with malnutrition (7%; 3-11%) was also present. Male gender and low socio-economic status increased the odds of infectious diseases and malnutrition, respectively. Malarial infection, chronic malnutrition and VAD remain the predominant health problems among these Ghanaian adolescents. Investigating the relationships with evolving CRFs is warranted.
A comparative study on the nutritional status of primiparous and multiparous women in the first trimester of pregnancy was conducted in the northeastern province of Thailand, Khon Kaen, to investigate differences in protein- energy-mal nutrition, iron deficiency anaemia, vitamin A deficiency and carotenoid status between both parity groups. 94 subjects were recruited at first attendance of antenatal clinic. Data about weight, height, haemoglobin and haematocrit were obtained from hospital records. Anthropometric measurements of mid-upper arm circumference and triceps skinfold were done on a sub sample. Retinol, carotenoids and alpha-tocopherol were analysed using a reversed-phase high- performance liquid chromatography method. Ferritin, transthyretin and retinol-binding protein were determined by enzyme- linked immunosorbent assay. Primiparous women showed lower body mass index, mid-upper arm circumference, corrected arm muscle area (P <0.001) as well as lower retinol, cholesterol and triceps skinfold (P <0.05). After adjusting for age and socio-economical status the significant difference persisted for all parameters but triceps skinfold. No significant differences of alpha-tocopherol, serum proteins, carotenoids and iron indices could be observed, even though a tendency to higher values for ferritin, haemoglobin and haematocrit was shown in multiparous women. Prevalence of protein-energy- malnutrition (body mass index <18.5 kg/m(2)) in the primiparous group was significantly higher compared to the multiparous group (P<0.05). Prevalence of protein-energy-malnutrition, iron deficiency anaemia and vitamin A deficiency were 15.1%, 6.3% and 3.3%, respectively, in the total study population. No differences between parity groups could be observed for prevalence of iron deficiency anaemia and vitamin A deficiency
Malnutrition, poor health, hunger, and even starvation are still the world's greatest challenges. Malnutrition is defined as deficiency of nutrition due to not ingesting the proper amounts of nutrients by simply not eating enough food and/or by consuming nutrient-poor food in respect to the daily nutritional requirements. Moreover, malnutrition and disease are closely associated and incidences of such diet-related diseases increase particularly in low- and middle-income states. While foods of animal origin are often unaffordable to low-income families, various neglected crops can offer an alternative source of micronutrients, vitamins, as well as health-promoting secondary plant metabolites. Therefore, agricultural and horticultural research should develop strategies not only to produce more food, but also to improve access to more nutritious food. In this context, one promising approach is to promote biodiversity in the dietary pattern of low-income people by getting access to nutritional as well as affordable food and providing recommendations for food selection and preparation. Worldwide, a multitude of various plant species are assigned to be consumed as grains, vegetables, and fruits, but only a limited number of these species are used as commercial cash crops. Consequently, numerous neglected and underutilized species offer the potential to diversify not only the human diet, but also increase food production levels, and, thus, enable more sustainable and resilient agro- and horti-food systems. To exploit the potential of neglected plant (NP) species, coordinated approaches on the local, regional, and international level have to be integrated that consequently demand the involvement of numerous multi-stakeholders. Thus, the objective of the present review is to evaluate whether NP species are important as “Future Food” for improving the nutritional status of humans as well as increasing resilience of agro- and horti-food systems.
Veränderung der Carotinoidkonzentration im Serum und in der Milch im Verlauf der Laktation der Frau
(2000)
Micronutrient deficiencies are widespread in developing countries, particularly in remote communities such as mobile pastoralists. The nutritional and vitamin A status of this population is not well-documented in Chad. This study assessed serum retinol levels among women and children under five-year-old in nomadic and semi-nomadic pastoralist and rural-settled communities, who are similarly exposed to risk factors such as gastrointestinal parasitic infection, anaemia and emaciation. The novel method of portable fluorometry was used for the first time to measure beta-carotene and retinol levels in a pastoral nomadic area. Moderate level blood retinol deficiency (< 0.7 mu mol/L) was observed in 5% (CI 1-11) of nomadic, 29% (CI 13-45) of semi-nomadic and 22% (CI 8-35) of sedentary women. In children, 1% (CI 0.1-4), 17% (CI 9-25) and 28% (CI 18-39), respectively, had moderate level blood retinol deficiency. In nomadic communities, women and children had blood retinol levels close to normal. Deficiency of retinol was strongly linked with lifestyle (nomadic, semi-nomadic and settled) among women and lifestyle and age among children. The results support an ecological linkage between human retinol levels and livestock milk retinol. This study shows the feasibility of portable retinol and beta-carotene measurement in human blood as well as human and animal milk under remote field conditions, but the approach requires further validation.
Objective: Retinol is transported in a complex with retinol-binding protein 4 (RBP4) and transthyretin (TTR) in the circulation. While retinol is associated with various cardiovascular risk factors, the relation between retinol, RBP4, TTR and carotid intima media thickness (IMT) has not been analysed yet. Methods: Retinol, RBP4 and TTR were measured in 96 individuals and their relation to mean and maximal IMT was determined. Results: Mean IMT correlated with RBP4 (r = 0.335, p < 0.001), retinol (r = -0.241, p = 0.043), RBP/TTR ratio (r = 0.254, p = 0.025) and retinol/RBP4 ratio (r = -0.549, p < 0.001). Adjustment for age, sex, BMI, blood pressure, HDL/total cholesterol ratio, triglyceride, diabetes and smoking revealed that the retinol/RBP4 ratio was strongly and independently associated with mean IMT. Similar results were found for maximal IMT, which included the measurement of plaques. Conclusion: The data support that the transport complex of vitamin A is associated with the IMT, an established parameter of atherosclerosis. Changes in RBP4 saturation with retinol may link renal dysfunction and insulin resistance to atherosclerosis.
Research in rodents has shown that dietary vitamin A reduces body fat by enhancing fat mobilisation and energy utilisation; however, their effects in growing dogs remain unclear. In the present study, we evaluated the development of body weight and body composition and compared observed energy intake with predicted energy intake in forty-nine puppies from two breeds (twenty-four Labrador Retriever (LAB) and twenty-five Miniature Schnauzer (MS)). A total of four different diets with increasing vitamin A content between 5.24 and 104.80 mu mol retinol (5000-100 000 IU vitamin A)/4184 kJ (1000 kcal) metabolisable energy were fed from the age of 8 weeks up to 52 (MS) and 78 weeks (LAB). The daily energy intake was recorded throughout the experimental period. The body condition score was evaluated weekly using a seven-category system, and food allowances were adjusted to maintain optimal body condition. Body composition was assessed at the age of 26 and 52 weeks for both breeds and at the age of 78 weeks for the LAB breed only using dual-energy X-ray absorptiometry. The growth curves of the dogs followed a breed-specific pattern. However, data on energy intake showed considerable variability between the two breeds as well as when compared with predicted energy intake. In conclusion, the data show that energy intakes of puppies particularly during early growth are highly variable; however, the growth pattern and body composition of the LAB and MS breeds are not affected by the intake of vitamin A at levels up to 104.80 mu mol retinol (100 000 IU vitamin A)/4184 kJ (1000 kcal).
Research in rodents has shown that dietary vitamin A reduces body fat by enhancing fat mobilisation and energy utilisation; however, their effects in growing dogs remain unclear. In the present study, we evaluated the development of body weight and body composition and compared observed energy intake with predicted energy intake in forty-nine puppies from two breeds (twenty-four Labrador Retriever (LAB) and twenty-five Miniature Schnauzer (MS)). A total of four different diets with increasing vitamin A content between 5.24 and 104.80 mu mol retinol (5000-100 000 IU vitamin A)/4184 kJ (1000 kcal) metabolisable energy were fed from the age of 8 weeks up to 52 (MS) and 78 weeks (LAB). The daily energy intake was recorded throughout the experimental period. The body condition score was evaluated weekly using a seven-category system, and food allowances were adjusted to maintain optimal body condition. Body composition was assessed at the age of 26 and 52 weeks for both breeds and at the age of 78 weeks for the LAB breed only using dual-energy X-ray absorptiometry. The growth curves of the dogs followed a breed-specific pattern. However, data on energy intake showed considerable variability between the two breeds as well as when compared with predicted energy intake. In conclusion, the data show that energy intakes of puppies particularly during early growth are highly variable; however, the growth pattern and body composition of the LAB and MS breeds are not affected by the intake of vitamin A at levels up to 104.80 mu mol retinol (100 000 IU vitamin A)/4184 kJ (1000 kcal).
Exercise may increase reactive oxygen species production, which might impair cell integrity and contractile function of muscle cells. However, little is known about the effect of regular exercise on the antioxidant status of adolescents. Purpose: This study aimed to evaluate the impact of exercise on the antioxidant status and protein modifications in adolescent athletes. Methods: In 90 athletes and 18 controls (16 +/- 2 yr), exercise-related energy expenditure was calculated on the basis of a 7-d activity protocol. Antioxidant intake and plasma concentrations of alpha-tocopherol, carotenoids, and uric acid were analyzed. Plasma antioxidant activity was determined by Trolox equivalent (TE) antioxidant capacity and electron spin resonance spectrometry. Protein modifications were assessed with structural changes of transthyretin using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Data were analyzed by two-way ANOVA and post hoc by the Tukey-Kramer test (alpha = 0.05). Results: Antioxidant intake correlated with energy intake and was within the recommended daily allowance for vitamins C and E and beta-carotene. Plasma levels of neither nutritional antioxidants nor uric acid differed between the groups. TE antioxidant capacity was higher in athletes (men = 1.47 perpendicular to 0.2 mmol TE per liter, women = 1.45 perpendicular to 0.2 mmol TE per liter) compared with controls (men = 1.17 +/- 0.04 mmol TE per liter, women = 1.14 +/- 0.04 mmol TE per liter) and increased with exercise-related energy expenditure (P = 0.007). Transthyretin cysteinylation rate differed between the groups, with the highest rate of protein modifications in moderately active subjects (P = 0.007). Conclusions: Results suggest that if the nutritional choice of athletes is well balanced, enough antioxidants are provided to meet recommended amounts. Moreover, regular exercise increases blood antioxidant capacity in young athletes, whereas chronic exercise was not shown to promote protein modifications. Thus, in young athletes who are sufficiently supplied with antioxidants, beneficial effects of exercise on antioxidant status rather than on oxidative stress may be anticipated.
High vitamin A ingestion or high serum retinol have been postulated to increase the risk of fractures and osteoporosis by reduced bone mineral density (BMD). Retinol is carried and transported to the tissues bound to retinol binding protein 4 (RBP4) and transthyretin (TTR). The relationships between retinol, retinol transport protein, retinol binding protein 4 (RBP4) and transthyretin (TTR) and BMD and osteoporosis are unclear. To examine the association between retinol and RBP4 and TTR and osteoporosis, 73 osteoporotic and 71 normal Thai postmenopausal women were studied. RBP4 and retinol levels did not differ between the groups. Serum TTR was significantly higher in control than osteoporotic subjects (89.47 and 144.53 mu g/ml, respectively, p=0.003, Mann-Whitney U test). TTR was positively correlated with BMD at several sites, such as the total radius bone (r=0.172, p=0.008, Spearman rank test). Osteoporosis risk was analyzed with binary logistic regression. Lean elderly Thais with lower TTR levels had a higher risk of osteoporosis. RBP4 and retinol levels had no relationship with disease status among Thai post-menopausal women. These results suggest calcium, minerals, vitamins and the retinol transport protein, transthyretin may be involved in the pathogenesis of osteoporosis.
Aims: To investigate the genetic markers for osteoporosis bone mineral density by the genotyping of rs7041, rs4588 and rs1352845 in the DBP gene with either bone mineral density or serum 25-hydroxycholecalciferol, retinol and alpha-tocopherol, among 365 postmenopausal Thai women. Materials & methods: The DBP genotypes were analyzed by a PCR restriction fragment-length polymorphism method. Serum 25-hydroxycholecalciferol was assessed using a commercial chemiluminescent immunoassay. Serum retinol and alpha-tocopherol were measured by reverse-phase high-performance liquid chromatography. Results: After adjustment for age >50 years, elder Thai subjects with low BMI (<= 25 kg/m(2)) and carrying the rs4588 CC genotype had a higher risk of radial bone mineral density osteoporosis (odds ratio: 6.29; p = 0.048). The rs1352845 genotype also had a statistical association with total hip bone mineral density; however, it disappeared after adjustment for age and BMI. No association was found in fat-soluble vitamins with bone mineral density. Conclusion: DBP genotypes may influence the osteoporosis bone mineral density in postmenopausal Thai women.
Background: Sub-Saharan Africa is facing a double burden of malnutrition: vitamin A deficiency (VAD) prevails, whereas the nutrition-related chronic conditions type 2 diabetes (T2D) and hypertension are emerging. Serum retinol a VAD marker increases in kidney disease and decreases in inflammation, which can partly be attributed to alterations in the vitamin A transport proteins retinol-binding protein 4 (RBP4) and prealbumin. Kidney dysfunction and inflammation commonly accompany T2D and hypertension.
Objective: Among urban Ghanaians, we investigated the associations of T2D and hypertension with serum retinol as well as the importance of kidney function and inflammation in this regard.
Design: A hospital-based, case-control study in individuals for risk factors of T2D, hypertension, or both was conducted in Kumasi, Ghana (328 controls, 197 with T2D, 354 with hypertension, and 340 with T2D plus hypertension). In 1219 blood samples, serum retinol, RBP4, and prealbumin were measured. Urinary albumin and estimated glomerular filtration rate (eGFR) defined kidney function. C-reactive protein (CRP) >5 mg/L indicated inflammation. We identified associations of T2D and hypertension with retinol by linear regression and calculated the contribution of RBP4, prealbumin, urinary albumin, eGFR, and CRP to these associations as the percentages of the explained variance of retinol.
Results: VAD (retinol <1.05 mu mol/L) was present in 10% of this predominantly female, middle-aged, overweight, and deprived population. Hypertension, but not T2D, was positively associated with retinol (beta: 0.12; 95% CI: 0.08, 0,17), adjusted for age, sex, socioeconomic factors, anthropometric measurements, and lifestyle. In addition to RBP4 (72%) and prealbumin (22%), the effect of increased retinol on individuals with hypertension was mainly attributed to impaired kidney function (eGFR: 30%; urinary albumin: 5%) but not to inflammation.
Conclusions: In patients with hypertension, VAD might be underestimated because of increased serum retinol in the context of kidney dysfunction. Thus, the interpretation of serum retinol in sub-Saharan Africa should account for hypertension status.
Steatotic livers show increased hepatic damage and impaired regeneration after partial hepatectomy (PH) under ischemia/reperfusion (I/R), which is commonly applied in clinical practice to reduce bleeding. The known function of retinol-binding protein 4 (RBP4) is to transport retinol in the circulation. We examined whether modulating RBP4 and/or retinol could protect steatotic and nonsteatotic livers in the setting of PH under I/R. Steatotic and nonsteatotic livers from Zucker rats were subjected to PH (70%) with 60 minutes of ischemia. RBP4 and retinol levels were measured and altered pharmacologically, and their effects on hepatic damage and regeneration were studied after reperfusion. Decreased RBP4 levels were observed in both liver types, whereas retinol levels were reduced only in steatotic livers. RBP4 administration exacerbated the negative consequences of liver surgery with respect to damage and liver regeneration in both liver types. RBP4 affected the mobilization of retinol from steatotic livers, and this revealed actions of RBP4 independent of simple retinol transport. The injurious effects of RBP4 were not due to changes in retinol levels. Treatment with retinol was effective only for steatotic livers. Indeed, retinol increased hepatic injury and impaired liver regeneration in nonsteatotic livers. In steatotic livers, retinol reduced damage and improved regeneration after surgery. These benefits of retinol were associated with a reduced accumulation of hepatocellular fat. Thus, strategies based on modulating RBP4 could be ineffective and possibly even harmful in both liver types in the setting of PH under I/R. In terms of clinical applications, a retinol pretreatment might open new avenues for liver surgery that specifically benefit the steatotic liver. Liver Transpl 18:1198-1208, 2012.
Background and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of alpha-tocopherol and specific clinical outcomes in diabetic hemodialysis patients.
Design, settings, participants, & measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), alpha-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma alpha-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508).
Results Patients had a mean age of 66 8 years, and mean plasma alpha-tocopherol level was 22.8+/-9.6 mu mol/L. Levels of alpha-tocopherol were highly correlated to triglycerides (r=0.63, P<0.001). Patients in the lowest alpha-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratio(stroke)=1.56, 95% confidence interval=0.75-3.25; hazard ratio(mortality)=1.22, 95% confidence interval=0.89-1.69, respectively). There was no association between alpha-tocopherol and myocardial infarction, sudden death, or infectious death.
Conclusions Plasma alpha-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients.
Background. Patients on maintenance haemodialysis treatment experience an excessive risk of cardiovascular disease and mortality. The vitamin A concentration is known to be higher in these patients compared to the general population where elevated vitamin A concentrations are associated with adverse outcome. The impact of vitamin A on morbidity and mortality in end-stage renal disease patients is controversial and is the topic of this study.
Methods. We analysed plasma retinol and retinol-binding protein 4 (RBP4) in 1177 diabetic haemodialysis patients, who participated in the German Diabetes and Dialysis Study (median follow-up 4 years). By Cox regression analyses hazard ratios (HRs) were determined for pre-specified, adjudicated end points according to baseline concentrations.
Results. Patients had a mean age of 66 +/- 8 years, mean retinol and RBP4 concentrations of 3.28 (0.71-7.44) and 4.02 (1.28-10.1) mu mol/L, respectively. Patients with retinol concentrations in the first quartile (<2.6 mu mol/L) had an almost 2-fold increased risk of all-cause mortality compared to patients of the fourth quartile [>3.9 mu mol/L; HR 1.81, 95% confidence interval (CI) 1.43-2.30]. There was a strong association between low retinol and the risk of sudden cardiac death (SCD, HR 2.22, 95% CI 1.41-3.50) and fatal infection (HR 2.19, 95% CI 1.26-3.82). Patients with RBP4 concentrations in the lowest quartile (<3.0 mu mol/L) were more likely to die of any cause (HR 1.43, 95% CI 1.14-1.80), experience SCD (HR 1.97, 95% CI 1.28-3.03) and cardiovascular events (HR 1.43, 95% CI 1.10-1.85).
Conclusion. This large cohort study shows a strong association of low retinol and RBP4 concentrations with SCD and all-cause mortality in diabetic haemodialysis patients.
The aim of this study was to investigate differences in concentrations of vitamin A, transthyretin (TTR) and retinol-binding protein (RBP) between plasma and cerebrospinal fluid (CSF) in dogs. RBP was detected using ELISA, and both RBP and TTR by Western blot analysis after separation on SDS-PAGE. Vitamin A was determined by high performance liquid chromatography. RBP and TTR as well as vitamin A were detected in all samples but at substantially lower concentrations in CSF compared to plasma. RBP in dog plasma showed a similar molecular mass to that of humans, whereas canine TTR had a lower molecular mass. Comparison between plasma and CSF showed that both RBP and TTR were of lower molecular mass in CSF. In CSF, RBP and retinol were present at 10-100-fold lower concentrations compared to plasma. Retinyl esters were present only in minute amounts in 5/17 samples. In conclusion, the CSF of dogs compared to humans is significantly different in terms of both quality and quantity of transport proteins for vitamin A.
Two-thirds of the organic matrix in urinary stones consists of proteins. Their relationship to calculogenesis remains controversial with regard to their effect as inhibitors or promoters during stone formation. The purpose of the present study was to determine the differences in peptide and protein pattern between the urine of stone formers (n = 23) and control dogs (n = 12), as well as between organic matrix of different urinary stones (struvite n = 11, calcium oxalate n = 8, uric acid n = 4) using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Specific differences in protein and peptide profiles were found in the organic matrix of different mineral compositions. Characteristic differences were also found in urinary peptide and protein pattern especially in molecular masses below 20 kDa between affected and healthy dogs. Based on the obtained molecular masses they were in some cases tentatively identified as proteins that are known to be involved in stone formation in humans. The study shows that in dogs, specific-urinary peptides and proteins might be associated with urolithiasis. It indicates the importance to further characterize those proteins for possible diagnostic purposes in prognosis and therapy
Measurement of total urinary proteins in individuals that tested positive by urinary dipstick is a typical method for assessing the presence of potentially serious renal disorders. In the absence of such overt proteinuria, however, measurement of specific urinary proteins may be useful in the diagnosis of nephropathies and may provide greater insight into the pathogenesis. The urine of 28 dogs (16 with renal disease and 12 healthy) was evaluated to determine whether specific low-molecular-weight proteins or the pattern of protein excretion could also be used as a marker of tubular dysfunction in dogs. Specific proteins were assessed by immunological methods, whereas protein profiles were determined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (MS). In particular, changes in the excretion of retinol-binding protein (RBP) and Tamm-Horsfall protein (THP) appear to be of clinical relevance in the diagnosis of canine kidney diseases. The pattern of urinary protein and peptides revealed specific changes in abundance in dogs with renal disease at molecular masses (kD) of 11.58, 12.41, 12.60, 14.58, 20.95 (RBP), 27.85, and 65.69 (albumin). In conclusion, comparable proteins as in humans might be used as urinary markers for proximal (RBP) and distal (THP) tubular dysfunction in dogs. Surface-enhanced laser desorption/ionization time-of-flight MS is a promising tool for the study of kidney physiology and pathophysiology and might aid in the discovery of new biomarkers of renal disease
The carotenoid lutein can improve human health. Since only a fraction is absorbed from food, lutein supplementation might be recommended. Emulsions could be good carrier systems to improve the bioavailability of lutein. Six different emulsifier compositions were used in this study to prepare lutein-loaded emulsions: beta-lactoglobulin, beta-lactoglobulin/lecithin, Biozate 1, Biozate 1/lecithin, Been 20 and Tween 20/lecithin. The droplet size, resistance to creaming, lutein stability, cytotoxicity and lutein uptake by HT29 cells were investigated. The whey protein beta-lactoglobulin, the whey protein hydrolysate Biozate 1 and the combination with lecithin brought the most promising results. The small droplet sizes and resistance to creaming were an indication of physical stable emulsions. Furthermore, these emulsifiers prevented oxidation of lutein. The choice of emulsifier had a strong impact on the uptake by HT29 cells. The highest lutein absorption was observed with the combination of Biozate 1 and lecithin.
Background: Retinol-binding protein 4 (RBP4) levels are elevated in the serum of patients with kidney dysfunction. We recently showed that RBP4 isoforms including apo-RBP4 (RBP4 not bound to retinol) and RBP4 truncated at the C-terminus (RBP4-L, RBP4-LL) are increased in the serum of patients with kidney diseases but not in serum of patients with various liver diseases. The aim of this study was to investigate the effect of renal replacement therapy on RBP4 isoforms. Methods: We investigated serum levels of RBP4, apo-RBP4, holo-RBP4, RBP4-L, RBP4-LL, retinol and transthyretin (TTR) in 18 hemodialysis (HD) patients, 30 patients after renal transplantation (RTx) and in 35 healthy controls. RBP4 and TTR levels were measured by enzyme-linked immunosorbent assay, apo- and holo-RBP4 by native electrophoresis, retinol by high performance liquid chromatography and RBP4-L and RBP4-LL were analyzed by mass spectrometry. Results: HD and RTx patients had elevated RBP4, apo-RBP4 and RBP4-LL levels compared to controls. RTx patients had elevated amounts of RBP4-L compared to controls and elevated RBP4 and apo-RBP4 levels compared to HD patients. Conclusion: The results demonstrate a strong correlation between kidney function and RBP4 isoforms and provide data for investigating the relation of RBP4 and insulin resistance in these patients.
Retinol-binding protein 4 (RBP4) is an adipokine bound in plasma to transthyretin (TTR), which prevents its glomerular filtration and subsequent catabolism in the kidney. Alterations of this interaction have been Suggested to be implicated in the elevation of RBP4 that are thought to contribute to the development Of insulin resistance associated with obesity and type 2 diabetes mellitus (T2DM). However, the factors linking RBP4 to TTR in humans are not clear. Therefore, this Study evaluated parameters influencing the RBP4-TTR interaction and their relation to obesity and T2DM. The RBP4 and TTR levels were quantified in plasma of 16 lean controls, 28 overweight controls, and 14 overweight T2DM patients by enzyme-linked immunosorbent assay. Transthyretin isoforms involved in RBP4 binding were determined by linear matrix-assisted laser desorption/ionization-time of flight-mass spectrometry after RBP4 coimmunoprecipitation. Holo-RBP4 (retinol-bound) and apo-RBP4 (retinol-free) were assessed by immunoblotting using nondenaturating polyacrylamide gel electrophoresis. Plasma levels of both RBP4 and TTR did not differ among the groups of lean controls, overweight controls, and overweight T2DM subjects. Using RBP4 immunoprecipitation, 4 mass signals were observed for TTR representing native, S-cysteinylated, S-cysteinglycinylated, and S-glutathionylated TTR. No differences in peak intensity of TTR isoforms were observed among the groups. Moreover, no differences in the ratio of holo- and apo-RBP4 were evident. The results suggest that circulating RBP4 and TTR were not affected by human obesity or T2DM, which might be attributed to the absence of alterations of TTR isoforms and the ratio of holo- and apo-RBP4 that might modify the TTR-RBP4 interaction.
Retinoids are essential in vertebrate reproduction and embryonic development. All-trans-retinoic acid (ATRA) is tightly regulated during these processes. CYP26A1 is mainly responsible for its degradation. To study the role of CYP26A1 during implantation, we applied R115866, a CYP26A1-specific antagonist, to rats during early gestation days (GD). On GD 6.5 and 12 samples were collected and the number of embryos was evaluated. ATRA concentration increased in uterus and serum, mRNA expression of CYP26A1 and CRABP2 increased in the liver, but not in the uterus. Uterine COX1 and 17 beta HSD mRNA expression was decreased. The number of embryos on GD 12 was not altered in this setting. It can be concluded that uterine expression of the analyzed retinoid-response genes during early gestation is not altered by this R115866 treatment and instead indirectly via ATRA. From our experiment we cannot confirm that ATRA obtains a major influencing role in the regulation of embryonic implantation.
To study the role of the TTR-RBP4-ROH complex components (transthyretin, serum retinol binding protein, retinol) and of angiogenic factors PlGF (placental growth factor) and sFlt-1 (soluble fms-like tyrosine kinase-1) in pregnancies complicated by small for gestational age infants (SGA). Case control study conducted on maternal serum collected between 11 + 0 to 13 + 6 weeks of gestation. TTR, RBP4, ROH, PlGF and sFlt-1 were measured in SGA patients (birth weight < 10%) who delivered at term (n = 37) and before 37 weeks of gestation (n = 17) and in a matched control group with uneventful pregnancies (n = 37). We found decreased RBP4 in SGA patients that delivered fetuses < 3% and in fetuses delivered after the 37 weeks of gestation compared to controls [1.50 (95% CI 1.40-1.75) vs 1.62 (95% CI 1.47-1.98), p < 0.05]. Further, we found lower PlGF and sFlt-1 concentrations in SGA that delivered before 37 weeks of gestation compared to controls (respectively, PIGF and sFlt-1: 39.7 pg/ml (95% CI 32.3-66.3) vs 62.9 pg/ml (95% CI 45.2-78.4) and 906 pg/ml (95% CI 727-1626) vs 1610 pg/ml (95% CI 1088-212), p < 0.05). First trimester maternal serum RBP4 and angiogenic factors PlGF and sFlt-1 can differently predict the timing of delivery of pregnancies complicated by SGA fetuses.
Background: The objective of the study was to investigate the relationship between first trimester maternal serum levels of the TTR-RBP4-ROH complex components and the later insurgence of an altered glucose metabolism during pregnancy.
Methods: Retrospective case control study including 96 patients between the 12th and 14th week of gestation, 32 that developed gestational diabetes mellitus (GDM), respectively, 21 non-insulin-treated (dGDM) and 11 insulin-treated (iGDM), 20 large for gestational age fetuses (LGA) without GDM and 44 patients with normal outcome as control. Serum concentrations of RBP4 and TTR were assessed by ELISA; serum concentration of ROH by reverse-phase high performance liquid chromatography (rpHPLC). The molecular heterogeneity of TTR and RBP4 was analyzed after immunoprecipitation by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS).
Results: iGDM patients were characterized by reduced TTR, RBP4 and ROH compared to controls (respectively, iGDM vs. controls, mean +/- SD: TTR 3.96 +/- 0.89 mu mol/L vs. 4.68 +/- 1.21 mu mol/L, RBP4 1.13 +/- 0.25 mu mol/L vs. 1.33 +/- 0.38 mu mol/L and ROH 1.33 +/- 0.17 mu mol/L vs. 1.62 +/- 0.29 mu mol/L, p < 0.05). TTR containing Gly10 in place of Cys10 was lower in the iGDM group (p < 0.05) compared to controls. In the final logistic regression model ROH significantly predicted the diagnosis of iGDM (OR 0.93, 95% CI 0.87-0.98, p < 0.05).
Conclusions: First trimester maternal serum ROH, RBP4 and TTR represent potential biomarkers associated with the development of iGDM.
Great apes are the closest living relatives of humans. Physiological similarities between great apes and humans provide clues to identify which biological features in humans are primitive or derived from great apes. Vitamin A (VA) and carotenoid metabolism have been only partially studied in great apes, and comparisons between great apes and humans are not available. We aimed to investigate VA and carotenoid intake and plasma concentrations in great apes living in captivity, and to compare them to healthy humans. Dietary intakes of humans (n = 20) and, among the great apes, chimpanzees (n = 15) and orangutans (n = 5) were calculated. Plasma retinol (ROH), retinol-binding protein (RBP), retinyl esters, and major carotenoids were analyzed. The great ape diet was higher in VA than in humans, due to high intake of provitamin A carotenoids. Plasma ROH concentrations in great apes were similar to those in humans, but retinyl esters were higher in great apes than in humans. Differences in plasma carotenoid concentrations were observed between great apes and humans. Lutein was the main carotenoid in great apes, while P-carotene was the main carotenoid for humans. RBP concentrations did not differ between great apes and humans. The molar ratio of ROH to RBP was close to 1.0 in both great apes and humans. In conclusion, great apes show homeostatic ROH regulation, with high but physiological retinyl esters circulating in plasma. Furthermore, great apes show great selectivity in their plasmatic carotenoid concentration, which is not explained by dietary intake.
Background: Vitamin A (VA) and its derivates (retinoids) are important nutritional substances, which mediate their biological activity mainly via nuclear retinoid receptors. Maternal VA intake during lactation influences the VA content in milk and the VA status of the progeny. We investigated the effects of maternal supplementation during lactation and direct supplementation to the pups after weaning on the retinoid concentration in serum and liver of neonatal mice using high doses of VA. Methods: Dams were fed a basal (4,500 retinol equivalents/ kg diet) or a VA- supplemented (324,000 retinol equivalents/ kg diet) diet during lactation. Pups kept receiving the same diet after weaning. Serum and liver samples of the pups were collected during lactation at days 1, 3, 5, 7, and 14 and post-weaning at days 21 and 65 after birth. Samples were analysed for retinoids by high-performance liquid chromatography. Results: Maternal VA supplementation resulted in significantly higher concentrations of retinol, retinyl palmitate and retinyl stearate in serum of mice neonates at days 5, 7, 14, 21 and 65 after birth in comparison to the basal diet, whereas significantly higher concentrations were observed in liver at days 5, 14, 21 and 65 after birth. At day 7 after birth, a decrease in the liver retinoid concentrations occurred in the VA-supplemented diet. Conclusion: Our results show for the first time that supplementation with high doses of VA during the lactation period in mice can affect serum retinol concentrations in the neonates and report that day 7 after birth is a critical time in the tissue distribution of retinoids during postnatal development. Copyright (C) 2005 S. Karger AG, Basel
Retinoid- and carotenoid-enriched diets influence the ontogenesis of the immune system in mice
(2003)
Background There is a high mortality rate in patients with systemic inflammatory response syndrome (SIRS) or sepsis. Therefore, an early diagnosis and prognostic assessment is important for optimal therapeutic intervention. The objective of the study was to evaluate if baseline values and changes in serum C-reactive protein (CRP) might predict survival in dogs with SIRS and sepsis. Design Prospective study; July 2004 to July 2005. Setting Small Animal Clinic, Berlin, Clinic of Small Animal Medicine, Munich. Animals Sixty-one dogs. Measurements and Main Results For the CRP analysis blood was drawn on day 0, 1, and 2; CRP was measured using a commercial ELISA test kit. Thirteen dogs suffered from nonseptic SIRS and 48 dogs from sepsis. The 14-day survival rate was 61% (69% nonseptic SIRS, 58% sepsis). Serum CRP was higher in sick dogs compared with controls (P < 0.001). Over the 3-day period surviving dogs (n=31) displayed a significantly greater decrease in CRP than nonsurvivors (n=10) (P=0.001). No correlation was found between the initial CRP concentrations and the survival rate. The changes in CRP corresponded to the survival rate (P=0.01). Conclusion There was no significant relationship between the survival rate in dogs with nonseptic SIRS or sepsis and the initial serum CRP concentrations. There was a correlation between decreasing CRP concentrations and recovery from disease. However, the changes in CRP concentrations over a 3-day period correctly predicted survival in 94% of dogs and death in 30% of the dogs (false positive rate 22%).
Influence of hormone replacement therapy on proteomic pattern in serum of postmenopausal women
(2004)
Objectives: Proteomics approaches to cardiovascular biology and disease hold the promise of identifying specific proteins and peptides or modification thereof to assist in the identification of novel biomarkers. Method: By using surface-enhanced laser desorption and ionization time of flight mass spectroscopy (SELDI-TOF-MS) serum peptide and protein patterns were detected enabling to discriminate between postmenopausal women with and without hormone replacement therapy (HRT). Results: Serum of 13 HRT and 27 control subjects was analyzed and 42 peptides and proteins could be tentatively identified based on their molecular weight and binding characteristics on the chip surface. By using decision tree-based Biomarker Patterns (TM) Software classification and regression analysis a discriminatory function was developed allowing to distinguish between HRT women and controls correctly and, thus, yielding a sensitivity of 100% and a specificity of 100%. The results show that peptide and protein patterns have the potential to deliver novel biomarkers as well as pinpointing targets for improved treatment. The biomarkers obtained represent a promising tool to discriminate between HRT users and non-users. Conclusion: According to a tentative identification of the markers by their molecular weight and binding characteristics, most of them appear to be part of the inflammation induced acute-phase response. (c) 2004 Elsevier Ireland Ltd. All rights reserved
Background: Transthyretin (TTR), a traditional biomarker for nutritional and inflammatory status exists in different molecular variants of yet unknown importance. A truncated form of TTR has recently been described to be part of a set of biomarkers for the diagnosis of ovarian cancer. The main aim of the study was therefore to characterize differences in microheterogeneity between ascitic fluid and plasma of women affected with ovarian cancer and to evaluate the tumor site as the possible source of TTR. Methods: Subjects were 48 women with primary invasive epithelial ovarian cancer or recurrent ovarian carcinoma. The control group consisted of 20 postmenopausal women. TTR and retinol-binding protein (RBP) levels were measured by enzyme-linked immunoassay ( ELISA) and C-reactive protein (CRP) levels by a high- sensitivity latex particle turbidimetric assay. The molecular heterogeneity of TTR was analysed using immunoprecipitation and matrix-associated laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Presence of TTR in tumor tissue was determined with indirect peroxidase immunostaining. Results: TTR and RBP (mu g/ml) levels in serum were 148.5 +/- 96.7 and 22.5 +/- 14.8 in affected women compared to 363.3 +/- 105.5 and 55.8 +/- 9.3 in healthy postmenopausal women ( p < 0.01). In ascitic fluid, levels were 1.02 +/- 0.24 and 4.63 +/- 1.57 mu g/ml, respectively. The mean levels of TTR and RBP in serum showed a tendency to decrease with the severity of the disease and were lower in affected women whose CRP levels were > 40 mg/ml ( p = 0.08 for TTR; p < 0.05 for RBP). No differences in TTR microheterogeneity were observed between TTR isolated from serum of affected and healthy women or from ascitic fluid. TTR occurred rather consistently in four variants. Mass signals were at 13758 +/- 7, 13876 +/- 13 ( greatest intensity), 13924 +/- 21 and 14062 +/- 24 Da, representing native, S-cysteinylated, S-cysteinglycinylated and glutathionylated TTR, respectively. Serum of healthy and affected women as well as ascitic fluid contained the truncated fragment of TTR ( 12828 +/- 11 Da). No immunoreactive TTR was observed in the tumor sites. Conclusion: The severity of the cancer associated catabolism as well as the inflammation status affect serum TTR and RBP levels. Neither TTR nor its truncated form originates from tumor tissue and its occurrence in ascites may well reflect the filtration from blood into ascitic fluid
Fast and easy tests for quantifying fat-soluble vitamins such as vitamin E and vitamin A, as well as beta-carotene, in whole blood without a need to preprocess blood samples could facilitate assessment of the vitamin status of dairy cattle. The objective of this study was to validate a field-portable fluorometer/spectrophotometer assay for the rapid quantification of these vitamins in whole blood and plasma of dairy cows and calves. We measured the concentrations of vitamin E and beta-carotene in whole blood and plasma from 28 dairy cows and 11 calves using the iCheck test (Bio-Analyt GmbH, Teltow, Germany) and compared the results with the current analytical standard (HPLC) in 2 independent laboratories, one at the University of Potsdam (Germany) and at one at DSM Nutritional Products Ltd. (Kaiseraugst, Switzerland). For vitamin A, the HPLC measurements were done only in the laboratory in Germany. The whole-blood concentrations of vitamin E as determined by iCheck (blood-hematocritcorrected) ranged from 1.82 to 4.99 mg/L in dairy cows and 0.34 to 3.40 mg/L in calves. These findings were moderately correlated (R-2 = 0.66) with the values assessed by HPLC in dairy cattle (cows + calves). When calves were excluded, the correlation was higher (R-2 = 0.961). The beta-carotene and vitamin A values obtained by the reference method HPLC were highly correlated with the iCheck methods in whole blood (R-2 = 0.99 and 0.88, respectively). In plasma, we observed strong correlations between the concentrations assessed by iCheck and those of HPLC for vitamin E (R-2 = 0.97), beta-carotene (R-2 = 0.98), and vitamin A (R-2 = 0.92) in dairy cattle (cows + calves). For vitamin E, beta-carotene, and vitamin A, we compared the relationship between the differences obtained by the iCheck assay and the HPLC measurements, as well as the magnitude of measurements, using Bland-Altman plots to test for systematic bias. For all 3 vitamins, the differences values were not outside the 95% acceptability limits; we found no systematic error between the 2 methods for all 3 analytes.
Objective-To evaluate vascular endothelial growth factor (VEGF) concentrations in canine blood products treated with or without a leukoreduction filter.
Sample-10 canine blood donors.
Procedures-Dogs underwent blood collection. Five of 10 units were leukoreduced prior to separation into packed RBCs and fresh frozen plasma (FFP). Concentrations of VEGF were measured by ELISA in plasma supernatants from aliquots of packed RBCs obtained immediately after separation and on days 7, 14, and 21 of storage. Fresh frozen plasma samples of 2 filtered and 2 nonfiltered units were examined after storage.
Results-RBC counts in whole blood before and after leukoreduction did not differ significantly, but WBCs and platelets were removed effectively. The VEGF concentration was lower than the detection limit (9 pg/mL) in 9 of 10 plasma samples and in all packed RBC and FFP units immediately after separation. The median VEGF concentrations in 5 nonfiltered packed RBC units were 37, 164, and 110 pg/mL on days 7, 14, and 21 of storage, respectively. In 5 filtered packed RBC and all FFP units, VEGF concentrations remained lower than the detection limit.
Conclusions and Clinical Relevance-Leukoreduction filters were effective in preventing the release of VEGF during storage of canine RBC products.
Background Canine primary immune-mediated hemolytic anemia (IMHA) is associated with a high-mortality rate. C- reactive protein (CRP) is the most important acute-phase protein in dogs and may have value as a marker of prognosis or response to treatment in IMHA. Objective The objectives of this study were to evaluate serum CRP concentration in dogs with primary IMHA at presentation and during treatment, to assess potential differences based on survival time, and to compare CRP with other laboratory parameters of inflammation and prognosis. Methods Inclusion criteria for primary IMHA were anemia (PCV < 0.30 L/L), a positive Coombs' test or persistent autoagglutination of erythrocytes, and the exclusion of underlying diseases by other diagnostic tests. Dogs were divided into 2 groups based on survival: dogs that were still alive 14 days after start of treatment (group 1) and dogs that died or were euthanized before day 14 (group 2). Serum CRP concentration, a CBC, and a biochemistry profile were performed on days 0, 3, 8, and 14. Serum CRP also was determined in 25 clinically healthy dogs. Results CRP concentration in the 25 clinically healthy dogs ranged from 0- 8.9 mu g/mL (median 2.2 mu g/mL). Thirty dogs were diagnosed with primary IMHA, 24 in group 1 and 6 in group 2. On day 0, CRP concentration in dogs in both groups (median 224 mu g/mL) was increased above the reference interval. In group 1 dogs, median CRP concentration was 242 mu g/mL on day 0, 69 mu g/mL on day 3, 35 mu g/mL on day 8, and 2 mu g/mL on day 14. In group 2 dogs, median CRP concentration was 194 mu g/mL on day 0, 119 mu g/mL on day 3, and 41 mu g/mL on day 8; only 1 dog in group 2 survived to day 8. There was a significant correlation between CRP and total WBC concentrations on days 0 and 3 (r=-.598, P=.003). Conclusions Serum CRP concentration was markedly increased in dogs with primary IMHA. CRP concentration did not differ based on patient survival, but might be a marker for long-term monitoring of these patients.
Physiologie der Laktation
(2000)
Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists. Thus, our findings uncover the existence of endocytic pathways for protein bound androgens and estrogens and their crucial role in development of the reproductive organs
Although horses and donkeys belong to the same genus, their genetic characteristics probably result in specific proteomes and post-translational modifications (PTM) of proteins. Since PTM can alter protein properties, specific PTM may contribute to species-specific characteristics. Therefore, the aim of the present study was to analyse differences in serum protein profiles of horses and donkeys as well as mules, which combine the genetic backgrounds of both species. Additionally, changes in PTM of the protein transthyretin (TTR) were analysed. Serum protein profiles of each species (five animals per species) were determined using strong anion exchanger ProteinChips (R) (Bio-Rad, Munich, Germany) in combination with surface-enhanced laser desorption ionisation-time of flight MS. The PTM of TTR were analysed subsequently by immunoprecipitation in combination with matrix-assisted laser desorption ionisation-time of flight MS. Protein profiling revealed species-specific differences in the proteome, with some protein peaks present in all three species as well as protein peaks that were unique for donkeys and mules, horses and mules or for horses alone. The molecular weight of TTR of horses and donkeys differed by 30Da, and both species revealed several modified forms of TTR besides the native form. The mass spectra of mules represented a merging of TTR spectra of horses and donkeys. In summary, the present study indicated that there are substantial differences in the proteome of horses and donkeys. Additionally, the results probably indicate that the proteome of mules reveal a higher similarity to donkeys than to horses.
Although horses and donkeys belong to the same genus, their genetic characteristics probably result in specific proteomes and post-translational modifications (PTM) of proteins. Since PTM can alter protein properties, specific PTM may contribute to species-specific characteristics. Therefore, the aim of the present study was to analyse differences in serum protein profiles of horses and donkeys as well as mules, which combine the genetic backgrounds of both species. Additionally, changes in PTM of the protein transthyretin (TTR) were analysed. Serum protein profiles of each species (five animals per species) were determined using strong anion exchanger ProteinChips (R) (Bio-Rad, Munich, Germany) in combination with surface-enhanced laser desorption ionisation-time of flight MS. The PTM of TTR were analysed subsequently by immunoprecipitation in combination with matrix-assisted laser desorption ionisation-time of flight MS. Protein profiling revealed species-specific differences in the proteome, with some protein peaks present in all three species as well as protein peaks that were unique for donkeys and mules, horses and mules or for horses alone. The molecular weight of TTR of horses and donkeys differed by 30Da, and both species revealed several modified forms of TTR besides the native form. The mass spectra of mules represented a merging of TTR spectra of horses and donkeys. In summary, the present study indicated that there are substantial differences in the proteome of horses and donkeys. Additionally, the results probably indicate that the proteome of mules reveal a higher similarity to donkeys than to horses.
OBJECTIVE-BMI and albumin are commonly accepted parameters to recognize wasting in dialysis patients and are powerful predictors of morbidity and mortality. However, both parameters reveal limitations and may not cover the entire range of patients with wasting. The visceral protein transthyretin (TTR) may be helpful in overcoming the diagnostic and prognostic gap. Therefore, the aim of this study was to assess the association of TTR with morbidity and mortality in hemodialysis patients.
RESEARCH DESIGN AND METHODS-The TTR concentration was determined in plasma samples of 1,177 hemodialysis patients with type 2 diabetes. Cox regression analyses were used to determine hazard ratios (HRs) for the risk of cardiovascular end points (CVEs) and mortality according to quartiles of TTR concentration for the total study cohort and the subgroups BMI >= 23 kg/m(2), albumin concentration >= 3.8 g/dL, and a combination of both.
RESULTS-A low TTR concentration was associated with an increased risk for CVE for the total study cohort (HR 1.65 [95% CI 1.27-2.14]), patients with BMI >= 23 kg/m(2) (1.70 [1.22-2.37]), albumin >= 3.8 g/dL (1.68 [1.17-2.42]), and the combination of both (1.69 [1.13-2.53]). Additionally, a low TTR concentration predicted mortality for the total study cohort (1.79 [1.43-2.24]) and patients with BMI >= 23 kg/m(2) (1.46 [1.09-1.95]).
CONCLUSIONS-The current study demonstrated that TTR is a useful predictor for cardiovascular outcome and mortality in diabetic hemodialysis patients. TTR was particularly useful in patients who were not identified to be at risk by BMI or albumin status.
Retinol-binding protein 4 (RBP4) is elevated in patients with chronic kidney disease (CKD) and has been discussed as marker of kidney function. In addition to an elevated concentration, the existence of truncated RBP4 species, RBP4-L (truncated at last C-terminal leucine) and RBP4-LL (truncated at both C-terminal leucines), has been reported in serum of hemodialysis patients. Since little is known about the occurrence of RBP4 species during the progression of CKD it was the aim of this study to analyse this possible association. The presence of RBP4, RBP4-L, RBP4- LL and transthyretin (TTR) was assessed in serum of 45 healthy controls and 52 patients with stage 2-5 of CKD using ELISA and RBP4 immunoprecipitation with subsequent MALDI-TOF-MS analysis. A reduction of glomerular filtration rate was accompanied by a gradual elevation of RBP4 serum levels and relative amounts of RBP4-LL. Correlation analysis revealed a strong association of the RBP4-TTR ratio with parameters of lipid metabolism and with diabetes-related factors. In conclusion, RBP4 serum concentration and the appearance of RBP4-LL seem to be influenced by kidney function. Furthermore, the RBP4-TTR ratio may provide diagnostic potential with regard to metabolic complications in CKD patients.
The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time-and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.
The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time- and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization – time of flight – mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.
The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time- and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization – time of flight – mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.
Vitamin A metabolism is changed in donors after living-kidney transplantation an observational study
(2011)
Background: The kidneys are essential for the metabolism of vitamin A (retinol) and its transport proteins retinol-binding protein 4 (RBP4) and transthyretin. Little is known about changes in serum concentration after living donor kidney transplantation (LDKT) as a consequence of unilateral nephrectomy; although an association of these parameters with the risk of cardiovascular diseases and insulin resistance has been suggested. Therefore we analyzed the concentration of retinol, RBP4, apoRBP4 and transthyretin in serum of 20 living-kidney donors and respective recipients at baseline as well as 6 weeks and 6 months after LDKT.
Results: As a consequence of LDKT, the kidney function of recipients was improved while the kidney function of donors was moderately reduced within 6 weeks after LDKT. With regard to vitamin A metabolism, the recipients revealed higher levels of retinol, RBP4, transthyretin and apoRBP4 before LDKT in comparison to donors. After LDKT, the levels of all four parameters decreased in serum of the recipients, while retinol, RBP4 as well as apoRBP4 serum levels of donors increased and remained increased during the follow-up period of 6 months.
Conclusion: LDKT is generally regarded as beneficial for allograft recipients and not particularly detrimental for the donors. However, it could be demonstrated in this study that a moderate reduction of kidney function by unilateral nephrectomy, resulted in an imbalance of components of vitamin A metabolism with a significant increase of retinol and RBP4 and apoRBP4 concentration in serum of donors.
Background
The kidneys are essential for the metabolism of vitamin A (retinol) and its transport proteins retinol-binding protein 4 (RBP4) and transthyretin. Little is known about changes in serum concentration after living donor kidney transplantation (LDKT) as a consequence of unilateral nephrectomy; although an association of these parameters with the risk of cardiovascular diseases and insulin resistance has been suggested. Therefore we analyzed the concentration of retinol, RBP4, apoRBP4 and transthyretin in serum of 20 living-kidney donors and respective recipients at baseline as well as 6 weeks and 6 months after LDKT.
Results
As a consequence of LDKT, the kidney function of recipients was improved while the kidney function of donors was moderately reduced within 6 weeks after LDKT. With regard to vitamin A metabolism, the recipients revealed higher levels of retinol, RBP4, transthyretin and apoRBP4 before LDKT in comparison to donors. After LDKT, the levels of all four parameters decreased in serum of the recipients, while retinol, RBP4 as well as apoRBP4 serum levels of donors increased and remained increased during the follow-up period of 6 months.
Conclusion
LDKT is generally regarded as beneficial for allograft recipients and not particularly detrimental for the donors. However, it could be demonstrated in this study that a moderate reduction of kidney function by unilateral nephrectomy, resulted in an imbalance of components of vitamin A metabolism with a significant increase of retinol and RBP4 and apoRBP4 concentration in serum of donors.
It is assumed that effects of the thiol antioxidant N-acetylcysteine (NAC) are mediated by interaction with protein-associated cysteine residues, however, information on protein level in vivo are missing. Therefore, we analyzed NAC-induced modifications of the protein transthyretin (TTR) in plasma of hemodialysis patients in a randomized, placebo-controlled study. TTR was selected due to its low molecular weight and the free cysteine residue in the polypeptide chain, which is known to be extensively modified by formation of mixed disulfides. The intravenous application of NAC during a hemodialysis session resulted in a substantial increase of native TTR from median 15% (range 8.8%-30%) to median 40% (37-50) and reduction of S-cysteinylated TTR [51% (44-60) vs. 6.6% (2.4-10)]. Additionally the pronounced formation of a TTR-NAC adduct was detected. However, all these modifications seemed to be reversible. Additionally, in vitro incubation of plasma with NAC confirmed the in vivo results and indicated that changes in post-translational modification pattern of TTR were a function of NAC concentration. Based on these observations and the essential metabolic and biochemical role of protein-associated cysteine residues we hypothesize that the interaction of NAC with proteins may explain altered protein functions due to modification of cysteine residues. Antioxid. Redox Signal. 19, 1166-1172.
Lutein is an essential dietary carotenoid with health benefits and is inter alia responsible for the colouration of egg yolk. The relationship between lutein accumulation and egg yolk colouration was therefore studied in more detail. After feeding a low-luteine diet for 21 days, 14 birds (Lohmann brown hens aged 20 weeks) were fed a diet containing marigold (80 mg lutein/kg feed) and 14 other birds were fed a diet containing oleoresin (45 mg lutein/kg feed) for 21 days; for both groups of birds, this feeding period was followed by withdrawal for 21 days. The Roche Yolk Colour Fan (RYCF) score (0 to 15, where higher values denote greater colour intensity; R-2=0.87; P<0.01) and redness (R-2=0.89; P<0.01) increased with increasing lutein content of egg yolk. Total carotenoid content had a poor relationship with lightness (R-2=0.13; P>0.05) and yellowness (R-2=0.12; P>0.05) of the yolk. It may be concluded that increased lutein is potentially responsible for an increased RYCF score and redness (a*), but decreased yellowness (b*) and lightness (L*), of egg yolk.
Carotenoids accumulated in the egg yolk are of importance for two reasons. Firstly they are important pigments influencing customer acceptance and secondly they are essential components with positive health effects either as antioxidants or as precursor of vitamin A. Different analytical methods are available to quantitatively identify carotenoids from egg yolk such as spectrophotometric methods described by AOAC (Association of Official Analytical Chemists) and HPLC (High Performance Liquid Chromatography). Both methods have in common that they are time consuming, need a laboratory environment and well trained technical operators. Recently, a rapid lab-independent spectrophotometric method (iCheck, BioAnalyt GmbH, Germany) has been introduced that claims to be less time consuming and easy to operate. The aim of the current study was therefore to compare the novel method with the two standard methods. Yolks of 80 eggs were analysed as aliquots by the three methods in parallel. While both spectrometric methods are only able measure total carotenoids as total beta-carotene, HPLC enables the determination of individual carotenoids such lutein, zeaxanthin, canthaxanthin, beta-carotene and beta-apocarotenoic ester. In general, total carotenoids levels as obtained by AOAC were in average 27% higher than those obtained by HPLC. Carotenoid values obtained by the reference methods AOAC and HPLC are highly correlated with the iCheck method with r(2) of 0.99 and 0.94 for iCheck vs. AOAC and iCheck vs. HPLC, respectively (both p < 0.001). Bland Altman analysis showed that the novel iCheck method is comparable to the reference methods. In conclusion, the novel rapid and portable iCheck method is a valid and effective tool to determine total carotenoid of egg yolk under laboratory-independent conditions with little trained personal. (C) 2014 Elsevier Ltd. All rights reserved.
Lutein and its isomer zeaxanthin have gained considerable interest as possible nutritional ingredient in the prevention of age-related macular degeneration (AMD) in humans. Egg yolk is a rich source of these carotenoids. As an oxidative sensitive component, antioxidants such as -tocopherol (T) might contribute to an improved accumulation in egg yolk. To test this, chickens were fed lutein esters (LE) with and without -tocopherol as an antioxidant. After depletion on a wheat-soya bean-based lutein-poor diet for 21days, laying hens (n=42) were equally divided into three groups and fed the following diets for 21days: control (basal diet), a LE group (40mg LE/kg feed) and LE+T group (40mg LE plus 100mg T/kg feed). Eggs and blood were collected periodically. Carotenoids and -tocopherol in yolk and blood plasma were determined by HPLC. Egg yolk was also analysed for total carotenoids using a one-step spectrophotometric method (iCheck(())). Lutein, zeaxanthin, -tocopherol and total carotenoids in egg yolk were highest after 14days of feeding and decreased slightly afterwards. At the end of the trial, eggs of LE+T group contained higher amount of lutein (13.72), zeaxanthin (0.65), -tocopherol (297.40) and total carotenoids (21.6) compared to the LE group (10.96, 0.55, 205.20 and 18.0mg/kg, respectively, p<0.05). Blood plasma values of LE+T group contain higher lutein (1.3), zeaxanthin (0.06) and tocopherol (20.1) compared to LE group (1.02, 0.04 and 14.90mg/l, respectively, p<0.05). In conclusion, dietary -tocopherol enhances bioavailability of lutein reflecting higher content in egg yolk and blood plasma. Improved bioavailability might be due to increased absorption of lutein in the presence of tocopherol and/or a greater stability of lutein/zeaxanthin due to the presence of -tocopherol as an antioxidant.
One-tube osmotic fragility (OF) test is a rapid test used widely for screening thalassemia in countries with limited resources. The test has important limitation in that its accuracy relies on observers’ experience.
The iCheck Turbidity is a prototype of portable nephelometer developed by BioAnalyt (Bioanalyt GmbH, Germany). In this study, we assessed the applicability of the iCheck Turbidity, for checking turbidity of the OF-test
Iron deficiency anemia, zinc and vitamin A deficiencies are serious public health problems in Cameroon, as in many developing countries. Local vegetables which are sources of provitamin A carotenoids (PACs) can be used to improve vitamin A intakes. However, traditional meals are often unable to cover zinc and iron needs. The aim of this study was to determine the bioavailability of 3 PACs (alpha-carotene, beta-carotene, and beta-cryptoxanthin) in young men, who were fed with a vitamin A-free diet and received iron and zinc supplementation. Twelve healthy participants were divided into three groups and were supplemented with elemental iron (20 mg of iron fumarate), 20 mg of zinc sulfate or iron + zinc (20 mg of iron in the morning and 20 mg of zinc in the evening) for 11 d. They were given a vitamin A- and PAC-free diet from the 6th to the 11th day, followed by a test meal containing 0.55 kg of freshly peeled papaya as a source of PACs. Blood samples were collected four times successively on the 11th day (the test meal day), at TO (just after the test meal), after 2 h (T2), after 4 h (T4) and after 7 h (T7). Ultracentrifugation was used to isolate serum chylomicrons. Retinol appearance and PAC postprandial concentrations were determined. The supplementation with zinc, iron and iron+zinc influenced the chylomicron appearance of retinol and PACs differently as reflected by retention times and maximum absorption peaks. Iron led to highest retinol levels in the chylomicron. Zinc and iron+zinc supplements were best for optimal intact appearance of alpha-carotene, beta-carotene and beta-cryptoxanthin respectively. Supplementation with iron led to the greatest bioavailability of PACs from papaya and its conversion to retinol.
Aim: To investigate the relationship of vitamin D-binding protein (GC) and genetic variation of GC (rs4588, rs7041 and rs2282679) with metabolic syndrome (MetS) in the Thai population. Materials & methods: GCglobulin concentrations were measured by quantitative western blot analysis in 401 adults. All participants were genotyped using TaqMan allelic discrimination assays. Results: GC-globulin levels were significatly lower in MetS subjects than in control subjects, in which significant negative correlations of GC-globulin levels with systolic blood pressure, glucose and age were found. Male participants who carried the GT genotype for rs4588 showed an increased risk of MetS compared with the GG wild-type (odds ratio: 3.25; p = 0.004). Conclusion: GC-globulin concentrations and variation in GC rs4588 were supported as a risk factor for MetS in Thais.
The aim of the present study was to investigate nutritional and metabolic parameters during the dry and early postpartum periods of ovulatory and anovulatory cows, as well as their postpartum reproductive performance. Blood samples from 20 multiparous Holstein cows were collected once a week from the far-off dry period to 3 weeks postpartum. Early postpartum (0-3 weeks) ovulation was confirmed using plasma progesterone concentration profiles, and cows were considered ovulatory if they had resumed luteal activity by this point (n = 9), whereas cows that had not were considered anovulatory (n = 11). Data from the ovulatory and anovulatory cows were analyzed separately for the far-off dry period (7-4 weeks prepartum), the close-up dry period (3-1 weeks prepartum), and the early postpartum period (0-3 weeks). Serum gamma-glutamyl transpeptidase activity (far-off, P = 0.065; close-up, P = 0.051; and early postpartum, P = 0.030) and aspartate aminotransferase (close-up, P = 0.050 and early postpartum, P = 0.087) activities were higher in anovulatory than in ovulatory cows. The days open period was longer (P = 0.019) in anovulatory than in ovulatory cows, and the number of artificial inseminations per conception (P = 0.025) was greater. In conclusion, we found that continuously high gamma-glutamyl transpeptidase activities in serum, which may be induced by liver disorders, prevent subsequent ovulation and affect subsequent fertility, even if cows obtain sufficient ovulation-related energy and beta-carotene.
beta-Carotene functions independently of vitamin A in the reproductive performance of dairy cows. The concentrations of beta-carotene in plasma decrease during the dry period, and reach a nadir in about the first week postpartum. This coincides with a negative energy balance, which affects the onset of the first ovulation in early postpartum cows. Thus, we hypothesised that plasma beta-carotene concentrations during the peripartum period may affect ovulation in the first follicular wave postpartum in dairy cows. The aim of the present study was to investigate changes in the profiles of plasma beta-carotene concentrations during the peripartum period in ovulatory and anovulatory cows during the first follicular wave postpartum. We used 22 multiparous Holstein cows, which were fed a total mixed ration consisting of grass, corn silage and concentrate, and collected blood samples for beta-carotene and progesterone analysis from week 3 prepartum to week 3 postpartum when the period of day 0-6 after parturition was regarded as the parturient week (week 0). The first ovulation was confirmed using the profile of plasma progesterone concentrations and colour Doppler ultrasound. Thirteen cows ovulated during the first postpartum follicular wave. Parity, the dry-off period, calving interval, mastitis episodes, and actual 305 days' milk yield during the previous lactation, and milk composition in the last month during the previous lactation in this study did not differ between ovulatory and anovulatory cows. Differences in the plasma beta-carotene profile were observed between ovulatory and anovulatory cows. Plasma P-carotene concentrations at week 3 prepartum were greater in ovulatory cows (2.97 +/- 0.24mg/L) than in anovulatory cows (1.53 +/- 0.14mg/L; P < 0.001), after that its concentrations in ovulatory cows decreased and reached the lowest level at week I postpartum, although its concentrations in anovulatory cows remained unchanged. No differences in plasma P-carotene concentrations between the two groups were observed postpartum. The present study indicates for the first time that the lower P-carotene concentrations in plasma during the prepartum period is associated with anovulation during the first follicular wave postpartum.
Tagetes spp. belongs to the Asteraceae family. It is recognized as a major source of lutein ester (lutein esterified with fatty acids such as lauric, myristic and palmitic acids), a natural colorant belonging to the xanthophylls or oxygenated carotenoids. Four species of Tagetes flower (Tagetes tenuifolia, Tagetes erecta, Tagetes patula, and Tagetes lucida) were used to extract lutein and lutein esters with three different methods. The results showed that T. erecta, type "orangeprinz", is the richest source of lutein esters (14.4 +/- 0.234 mg/g) in comparison to other Tagetes spp. No significant differences between extractions of lutein esters with medium-chain triacylglycerols (MCT) oil, orange oil or solvent (hexane/isopropanol) could be observed. MCT oil also improved stability of lutein esters at 100 degrees C for 40 min. Emulsification of MCT oil improved the stability of lutein ester extract against UV light at 365 nm for 72 h. Finally, an emulsion was prepared under food processing conditions, spray dried and its bioavailability investigated in a preliminary human intervention study. The results show a lower resorption, but further data suggest improvements in implementation of such supplements. (c) 2012 Elsevier Ltd. All rights reserved.
Background
Coronavirus disease (COVID-19) has a severe impact on all aspects of patient care. Among the numerous biomarkers of potential validity for diagnostic and clinical management of COVID-19 are biomarkers at the interface of iron metabolism and inflammation.
Methods
The follow-up study included 54 hospitalized patients with laboratory-confirmed COVID-19 with a moderate and severe/critical form of the disease. Iron deficiency specific biomarkers such as iron, ferritin, transferrin receptor, hepcidin, and zinc protoporphyrin (ZnPP) as well as relevant markers of inflammation were evaluated twice: in the first five days when the patient was admitted to the hospital and during five to 15 days; and their validity to diagnose iron deficiency was further assessed. The regression and Receiver Operating Characteristics (ROC) analyses were performed to evaluate the prognosis and determine the probability for predicting the severity of the disease in the first five days of COVID-19.
Results
Based on hemoglobin values, anemia was observed in 21 of 54 patients. Of all iron deficiency anemia-related markers, only ZnPP was significantly elevated (P<0.001) in the anemic group. When patients were grouped according to the severity of disease, slight differences in hemoglobin or other anemia-related parameters could be observed. However, the levels of ZnPP were significantly increased in the severely ill group of patients. The ratio of ZnPP to lymphocyte count (ZnPP/L) had a discrimination power stronger than the neutrophil to lymphocyte count ratio (N/L) to determine disease severity. Additionally, only two markers were independently associated with the severity of COVID-19 in logistic regression analysis; D-dimer (OR (5.606)(95% CI 1.019–30.867)) and ZnPP/L ratio (OR (74.313) (95% CI 1.081–5108.103)).
Conclusions
For the first time ZnPP in COVID-19 patients were reported in this study. Among all iron-related markers tested, ZnPP was the only one that was associated with anemia as based on hemoglobin. The increase in ZnPP might indicate that the underlying cause of anemia in COVID-19 patients is not only due to the inflammation but also of nutritional origin. Additionally, the ZnPP/L ratio might be a valid prognostic marker for the severity of COVID-19.
Background
Coronavirus disease (COVID-19) has a severe impact on all aspects of patient care. Among the numerous biomarkers of potential validity for diagnostic and clinical management of COVID-19 are biomarkers at the interface of iron metabolism and inflammation.
Methods
The follow-up study included 54 hospitalized patients with laboratory-confirmed COVID-19 with a moderate and severe/critical form of the disease. Iron deficiency specific biomarkers such as iron, ferritin, transferrin receptor, hepcidin, and zinc protoporphyrin (ZnPP) as well as relevant markers of inflammation were evaluated twice: in the first five days when the patient was admitted to the hospital and during five to 15 days; and their validity to diagnose iron deficiency was further assessed. The regression and Receiver Operating Characteristics (ROC) analyses were performed to evaluate the prognosis and determine the probability for predicting the severity of the disease in the first five days of COVID-19.
Results
Based on hemoglobin values, anemia was observed in 21 of 54 patients. Of all iron deficiency anemia-related markers, only ZnPP was significantly elevated (P<0.001) in the anemic group. When patients were grouped according to the severity of disease, slight differences in hemoglobin or other anemia-related parameters could be observed. However, the levels of ZnPP were significantly increased in the severely ill group of patients. The ratio of ZnPP to lymphocyte count (ZnPP/L) had a discrimination power stronger than the neutrophil to lymphocyte count ratio (N/L) to determine disease severity. Additionally, only two markers were independently associated with the severity of COVID-19 in logistic regression analysis; D-dimer (OR (5.606)(95% CI 1.019–30.867)) and ZnPP/L ratio (OR (74.313) (95% CI 1.081–5108.103)).
Conclusions
For the first time ZnPP in COVID-19 patients were reported in this study. Among all iron-related markers tested, ZnPP was the only one that was associated with anemia as based on hemoglobin. The increase in ZnPP might indicate that the underlying cause of anemia in COVID-19 patients is not only due to the inflammation but also of nutritional origin. Additionally, the ZnPP/L ratio might be a valid prognostic marker for the severity of COVID-19.
Analyses of the correlation between dermal and blood carotenoids in female cattle by optical methods
(2013)
Herd health programs for the maintenance of welfare and productivity in cattle need efficient tools for monitoring the health of individual animals. Recent reports demonstrate that the oxidative status is related to various stress conditions in dairy cows. Biomarkers, among other carotenoids, could serve as indicators of stress originating from the environment (e.g., heat stress or sun radiation) or from the animal itself (e.g., disease). To date, only invasive in vitro tests are available to assess the oxidative status in cattle. The present study compares the results of optical noninvasive in vivo measurements of dermal carotenoids in cattle udder skin using an LED-based miniaturized spectroscopic system (MSS) with those obtained by photometric analysis of beta carotene in whole blood samples using a portable device. Correlations between the concentrations of dermal and blood carotenoids were calculated under consideration of the nutritional status of the animals. Significant correlation (R = 0.86) was found for cattle with a moderate to obese body condition. Thus, the blood and skin concentrations of the marker substance beta carotene are comparable under stable stress conditions of the cattle. This demonstrates that the MSS is suitable for noninvasive assessment of dermal carotenoid concentrations in cattle.
Du sollst nicht essen
(2024)
Zwar sind Menschen biologisch gesehen Allesesser, dennoch gibt es keine Gemeinschaft, die alle ihr zur Verfügung stehenden Nahrungsmittel voll ausschöpft. Immer wird etwas nicht gegessen. Warum wir nicht essen, was wir nicht essen – das beleuchtet dieser Sammelband aus neuro-, ernährungs-, gesellschafts- und religionswissenschaftlicher Perspektive. Ein „religiöser Nutriscore“ gibt Auskunft über die wichtigsten Verzichtsregeln in Judentum, Christentum und Islam. Eine Fotostrecke veranschaulicht, wie bestimmte Speisen zu Festen und Feiertagen zu einem heiligen Essen werden. Nicht zuletzt werden Wege aufgezeigt, wie Menschen, die verschiedene Speiseregeln befolgen, dennoch zusammen essen können – inklusive Praxistest in der Unimensa.
Du sollst nicht essen
(2024)
Zwar sind Menschen biologisch gesehen Allesesser, dennoch gibt es keine Gemeinschaft, die alle ihr zur Verfügung stehenden Nahrungsmittel voll ausschöpft. Immer wird etwas nicht gegessen. Warum wir nicht essen, was wir nicht essen – das beleuchtet dieser Sammelband aus neuro-, ernährungs-, gesellschafts- und religionswissenschaftlicher Perspektive. Ein „religiöser Nutriscore“ gibt Auskunft über die wichtigsten Verzichtsregeln in Judentum, Christentum und Islam. Eine Fotostrecke veranschaulicht, wie bestimmte Speisen zu Festen und Feiertagen zu einem heiligen Essen werden. Nicht zuletzt werden Wege aufgezeigt, wie Menschen, die verschiedene Speiseregeln befolgen, dennoch zusammen essen können – inklusive Praxistest in der Unimensa.
In this study, effects of oral beta-carotene supplementation to mares (beta-carotene group: 1000 mg/day, n = 15; control group: n = 15) from 2 weeks before foaling until 6 weeks thereafter on concentrations of beta-carotene, vitamin A and a-tocopherol in plasma, colostrum and milk and plasma of their foals were determined. In addition, effects on fertility were studied. Beta-carotene concentrations increased in plasma and colostrum of beta-carotene-supplemented mares compared to control mares (p < 0.05). In mares of both groups, beta-carotene concentrations were higher in colostrum than in milk (p < 0.05). In foals, beta-carotene concentrations increased with colostrum uptake and were higher in foals born to supplemented mares (p < 0.05; control group: 0.0003 +/- 0.0002 mu g/ml on day 0, 0.008 +/- 0.0023 mu g/ml on day 1; beta-carotene group: 0.0005 +/- 0.0003 mu g/ml on day 0, 0.048 +/- 0.018 mu g/ml on day 1). Concentrations of vitamin A and a-tocopherol were higher in colostrum than in milk (p < 0.05) but did not differ between groups. Concentration of a-tocopherol in plasma of mares decreased over time and in foals, increased markedly within 4 days after birth. All but one mare (control group) showed oestrus within 2 weeks post-partum. Occurrence of oestrus did not differ between groups. More mares of the control group (7/7 vs. 5/12 in the beta-carotene group) became pregnant after being bred in first post-partum oestrus (p < 0.05). In conclusion, beta-carotene supplementation to mares increased beta-carotene concentrations in plasma, colostrum and milk of mares and plasma of their foals but had no positive effects on fertility.
Changes in faecal bacteria and metabolic parameters in foals during the first six weeks of life
(2011)
Many foals develop diarrhoea within the first two weeks of life which has been suggested to coincide with postpartum oestrus in their dams. To analyse the pathogenesis of this diarrhoea we have determined faecal bacteria in foals and their dams (n = 30 each), and serum IGF-1 and gamma-globulins for 6 weeks after birth. In addition, effects of beta-carotene supplementation to mares (group 1: 1000 mg/day, n = 15, group 2: control, n = 15) on diarrhoea in foals were studied. Diarrhoea occurred in 92 and 79% of foals in groups 1 and 2, respectively, but was not correlated with oestrus in mares. Beta-carotene supplementation was without effect on foal diarrhoea. In mares, bacterial flora remained stable. The percentage of foals with cultures positive for E. coli was low at birth but increased within one day, the percentage positive for Enterococcus sp. was low for 10 days and for Streptococcus sp. and Staphylococcus sp. was low for 2-4 weeks. By 4 weeks of age, bacterial flora in foals resembled an adult pattern. Concentration of serum IGF-1 was low at birth (group 1:149 +/- 11, group 2:166 17 ng/ml), increased after day 1 (day 7 group 1:384 +/- 30, group 2: 372 +/- 36) but at no time differed between groups. Serum gamma-globulin concentration in foals was low before colostrum intake and highest on day 1 (p < 0.001 over time). In conclusion, neonatal diarrhoea in foals does not coincide with postpartum oestrus in their dams but with changes in intestinal bacteria and is not influenced by beta-carotene supplementation given to mares.
Background: Retinol binding protein 4 (RBP4), a protein secreted by adipocytes and bound in plasma to transthyretin (TTR), has been associated with obesity, the early phase of insulin resistance, metabolic syndrome, and type 2 diabetes mellitus. The objective of this study was to elucidate the relationship between RBP4, TTR, triglyceride (TG) and type 2 diabetes risk in rural Thailand. Results: RBP4 and TTR levels, as well as homeostatic model assessment of insulin resistance (HOMA-IR) values, were significantly elevated among subjects with high triglyceride levels (p < 0.01, p < 0.05, p < 0.05, respectively). Triglyceride levels correlated with RBP4 (r = 0.34, p < 0.001) and TTR (r= 0.26, p < 0.01) levels, as well as HOMA-IR values (r= 0.16, p < 0.05). After adjustment for age and gender, the risk of hypertriglyceridemia was 3.7 times greater (95% Cl =1.42 -9.73, p = 0.008) in the highest RBP4 tertile as compared to the lowest tertile. Similarly, the highest TTR and HOMA-IR tertiles had greater risk of hypertriglyceridemia at 3.5 (95% Cl = 1.30-9.20, p = 0.01) and 3.6 (95% CI = 1.33- 9.58, p = 0.01) times higher than the respective lowest tertiles. The correlation between TTR and blood glucose was statistically significant (r 0.18, p < 0.05), but not found this relationship in RBP4. Conclusions: The associations of RBP4 and TTR with hypertriglyceridemia and insulin resistance may have important implications for the risk of heart disease and stroke.
The effect of tannins on mediterranean ruminant ingestive behavior the role of the oral cavity
(2011)
Sheep, cattle and goat are domestic ruminants of significant economic interest in the Mediterranean region. Although sharing the same pasture ranges, they ingest different plants and plant parts and, consequently different levels of tannins. This suggests an ability to detect and adapt ingestion according to animal physiological limits of tolerance for plant secondary metabolites. This review will detail the effects of dietary tannins on feeding behavior, and the role of the oral cavity in this process, with focus on such ruminant species. The role of salivary protein profile in tannin perception in the oral cavity, and as a defense mechanism, will be discussed.
An imbalance between formation and detoxification of oxygen radicals leads to oxidant stress that may increase in more intense oxidative metabolism caused by a high intake of metabolizable energy to provide metabolic intermediates for the milk synthesis and secretion. This hypothesis was tested using dairy cows and the concentration of hydroperoxides in lipids (LHP) extracted from circulative lipoprotein particles of low and very low density (LDL and VLDL/chylomicrons) as oxidant stress indicator. The particles were prepared by ultracentrifugation of serum obtained by coccygeal bleeding (13 cows, 1. parity, n=8 and 2. parity, n=5, lactation stage, 53 +/- 1.4 days post partum) and purified by precipitation. Concentrations of LHP-LDL/mg Lipoprotein correlated significantly with daily milk yield (r = 0.73, P = 0.004) or daily milk energy output (r = 0.77, P = 0.003) in contrast to LHP of VLDL/chylomicron particles. Thus, some evidence was obtained for an almost linear, positive relationship between milk productivity and oxidant stress occurring in LDL
BACKGROUND/OBJECTIVES: Preterm infants have low vitamin A stores at birth, and parenteral administration of high-dose vitamin A reduces pulmonary morbidity. The aim was to characterize vitamin A transport and status.
SUBJECTS/METHODS: Prospective study of 69 preterm infants (median birth weight 995 g, gestational age 28 weeks), in which 51 received 5000 IU vitamin A three times per week intramuscular (i.m.) for 4 weeks and 18 infants without i.m. vitamin A served as controls. Serum retinol, retinyl palmitate, total retinol-binding protein 4 (RBP4), retinol-unbound RBP4 (apo-RBP4) and transthyretin concentrations were determined at days 3 (D3) and 28 (D28) of life.
RESULTS: D3 retinol concentrations were low for the entire group (382 (285/531) nmol/l; median/interquartile range) and unrelated to gestational age. D28 retinol was unchanged in controls (382 (280/471) nmol/l), but increased in the vitamin A group (596 (480/825) nmol/l; P < 0.001). A similar pattern was observed for RBP4. The calculated retinol-to-RBP4 ratio rose in vitamin A infants (D3: 0.81 (0.57/0.94), D28: 0.98 (0.77/1.26); P < 0.01) but not in controls. In the vitamin A group, the retinol-to-RBP4 ratio was 41 in 15% of all infants on D3 and in 45% of infants on D28, but was <= 1 in all, but one, controls on D28.
CONCLUSIONS: In preterm infants receiving a 4-week course of high-dose i. m. vitamin A, serum retinol concentrations increased by 55%, with molar concentrations of retinol exceeding those of RBP4 in 45% of the infants suggesting transport mechanisms other than RBP4.
The safe upper limit for inclusion of vitamin A in complete diets for growing dogs is uncertain, with the result that current recommendations range from 5.24 to 104.80 mu mol retinol (5000 to 100 000 IU vitamin A)/4184 kJ (1000 kcal) metabolisable energy (ME). The aim of the present study was to determine the effect of feeding four concentrations of vitamin A to puppies from weaning until 1 year of age. A total of forty-nine puppies, of two breeds, Labrador Retriever and Miniature Schnauzer, were randomly assigned to one of four treatment groups. Following weaning at 8 weeks of age, puppies were fed a complete food supplemented with retinyl acetate diluted in vegetable oil and fed at 1ml oil/100 g diet to achieve an intake of 5.24, 13.10, 78.60 and 104.80 mu mol retinol (5000, 12 500, 75 000 and 100 000 IU vitamin A)/4184 kJ (1000 kcal) ME. Fasted blood and urine samples were collected at 8, 10, 12, 14, 16, 20, 26, 36 and 52 weeks of age and analysed for markers of vitamin A metabolism and markers of safety including haematological and biochemical variables, bone-specific alkaline phosphatase, cross-linked carboxyterminal telopeptides of type I collagen and dual-energy X-ray absorptiometry. Clinical examinations were conducted every 4 weeks. Data were analysed by means of a mixed model analysis with Bonferroni corrections for multiple endpoints. There was no effect of vitamin A concentration on any of the parameters, with the exception of total serum retinyl esters, and no effect of dose on the number, type and duration of adverse events. We therefore propose that 104.80 mu mol retinol (100 000 IU vitamin A)/4184 kJ (1000 kcal) is a suitable safe upper limit for use in the formulation of diets designed for puppy growth.
The safe upper limit for inclusion of vitamin A in complete diets for growing dogs is uncertain, with the result that current recommendations range from 5.24 to 104.80 mu mol retinol (5000 to 100 000 IU vitamin A)/4184 kJ (1000 kcal) metabolisable energy (ME). The aim of the present study was to determine the effect of feeding four concentrations of vitamin A to puppies from weaning until 1 year of age. A total of forty-nine puppies, of two breeds, Labrador Retriever and Miniature Schnauzer, were randomly assigned to one of four treatment groups. Following weaning at 8 weeks of age, puppies were fed a complete food supplemented with retinyl acetate diluted in vegetable oil and fed at 1ml oil/100 g diet to achieve an intake of 5.24, 13.10, 78.60 and 104.80 mu mol retinol (5000, 12 500, 75 000 and 100 000 IU vitamin A)/4184 kJ (1000 kcal) ME. Fasted blood and urine samples were collected at 8, 10, 12, 14, 16, 20, 26, 36 and 52 weeks of age and analysed for markers of vitamin A metabolism and markers of safety including haematological and biochemical variables, bone-specific alkaline phosphatase, cross-linked carboxyterminal telopeptides of type I collagen and dual-energy X-ray absorptiometry. Clinical examinations were conducted every 4 weeks. Data were analysed by means of a mixed model analysis with Bonferroni corrections for multiple endpoints. There was no effect of vitamin A concentration on any of the parameters, with the exception of total serum retinyl esters, and no effect of dose on the number, type and duration of adverse events. We therefore propose that 104.80 mu mol retinol (100 000 IU vitamin A)/4184 kJ (1000 kcal) is a suitable safe upper limit for use in the formulation of diets designed for puppy growth.
This study investigated vitamin A compounds in the plasma of healthy free-ranging Central European raptors with different feeding strategies. Plasma samples of nestlings of white-tailed sea eagle [white-tailed sea eagle (WTSE), Haliaeetus albicilla) (n = 32), osprey (Pandion haliaetus) (n = 39), northern goshawk (Accipiter gentilis) (n = 25), common buzzard (Buteo buteo) (n = 31), and honey buzzard (Pernis apivorus) (n = 18) and adults of WTSE (n = 10), osprey (n = 31), and northern goshawk (n = 45) were investigated with reversed-phase-high-performance liquid chromatography (RP-HPLC). In WTSE, northern goshawks and common buzzards retinol were the main plasma component of vitamin A, whilst in ospreys and honey buzzards, 3,4-didehydroretinol predominated. The median of the retinol plasma concentration in the nestlings group ranged from 0.12 to 3.80 mu M and in the adult group from 0.15 to 6.13 mu M. Median plasma concentrations of 3,4-didehydroretinol in nestlings ranged from 0.06 to 3.55 mu M. In adults, northern goshawks had the lowest plasma concentration of 3,4-didehydroretinol followed by WTSE and ospreys. The plasma of all investigated species contained retinyl esters (palmitate, oleate, and stearate). The results show considerable species-specific differences in the vitamin A plasma concentrations that might be caused by different nutrition strategies.
In this study, we investigated the alpha-tocopherol plasma concentrations in healthy free-ranging nestlings of the white-tailed sea eagle (Haliaeetus albicilla) (n=32), osprey (Pandion haliaetus) (n=39), northern goshawk (Accipiter gentilis) (n=25), common buzzard (Buteo buteo) (n=31), and honey buzzard (Pernis apivorus) (n=18) as well as of free-ranging adults of the white-tailed sea eagle (n=10), osprey (n=31), and northern goshawk (n=45). alpha-Tocopherol plasma concentrations were determined by reverse-phase high-performance liquid chromatography. alpha-Tocopherol plasma concentrations in nestlings of osprey, white-tailed sea eagle, and northern goshawk did not differ significantly amongst the species, but the common buzzard and honey buzzard nestlings had significantly lower alpha-tocopherol plasma concentrations than nestlings of the other species (both P<0.001). Adult male ospreys and white-tailed sea eagles had significantly higher alpha-tocopherol concentrations compared to adult females (both P<0.005). Adult ospreys and northern goshawks had significantly higher alpha-tocopherol plasma concentrations compared to their nestlings (both P<0.001). In adult female northern goshawks, plasma concentrations of alpha-tocopherol increased significantly before egg laying (P<0.001). These results demonstrate alpha-tocopherol plasma concentrations in birds of prey to be species specific and influenced by age and reproductive status.
Vitamin A (VA) deficiency in very low birth weight (VLBW) infants is associated with an increased risk for disorders related to kidney and lung maturation and function. VA losses through increased urinary retinol (ROH) excretion might contribute to this deficiency risk. The mechanism accounting for ROH loss in the urine has not yet been clarified. The aim of this study was to assess the excretion of ROH, retinol-binding protein 4 (RBP4) and transthyretin (TTR) in urine from VLBW infants in comparison with that in term infants in relation to kidney function. Urine specimens were collected from 15 VLBW infants (birth weight < 1,500 g) as well as from 20 term infants during the first 2 days after birth. ROH in urine was detectable in 14 of the 15 VLBW infants at a median concentration of 234 nmol/g creatinine. In the group of term infants, 17 of the 20 excreted ROH, but at an approximately five-times lower concentration (P<0.001). Excretion of RBP4 and TTR was also much higher in VLBW infants (both P<0.001). The urinary ROH excretion in VLBW infants may be related to the impaired tubular handling of its carrier proteins RBP4 and TTR. Thus, ROH excretion might contribute to an increased risk of VA deficiency, especially in VLBW infants.
Background Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken. Results Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D-2 and 25(OH)D-3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001). Conclusions In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P.
Background
Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken.
Results
Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D-2 and 25(OH)D-3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001).
Conclusions
In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P.
Verteilung von Vitamin A und Retinol-Bindungs-Protein (RBP) in verschiedenen Geweben von Caniden
(1997)
Background: beta-Carotene is an important precursor of vitamin A, and is associated with bovine fertility. beta-Carotene concentrations in plasma are used to optimize beta-carotene supplementation in cattle, but measurement requires specialized equipment to separate plasma and extract and measure beta-carotene, either using spectrophotometry or high performance liquid chromatography (HPLC).
Objective: The objective of this study was to validate a new 2-step point-of-care (POC) assay for measuring beta-carotene in whole blood and plasma.
Methods: beta-carotene concentrations in plasma from 166 cows were measured using HPLC and compared with results obtained using a POC assay, the iCheck-iEx-Carotene test kit. Whole blood samples from 23 of these cattle were also evaluated using the POC assay and compared with HPLC-plasma results from the same 23 animals. The POC assay includes an extraction vial (iEx Carotene) and hand-held photometer (iCheck Carotene).
Results: Concentrations of beta-carotene in plasma measured using the POC assay ranged from 0.40 to 15.84 mg/L (n = 166). No differences were observed between methods for assay of plasma (mean +/- SD; n = 166): HPLC-plasma 4.23 +/- 2.35 mg/L; POC-plasma 4.49 +/- 2.36 mg/L. Similar good agreement was found when plasma analyzed using HPLC was compared with whole blood analyzed using the POC system (n = 23): HPLC-plasma 3.46 +/- 2.12 mg/L; POC-whole blood 3.67 +/- 2.29 mg/L.
Conclusions: Concentrations of beta-carotene can be measured in blood and plasma from cattle easily and rapidly using a POC assay, and results are comparable to those obtained by the highly sophisticated HPLC method. Immediate feedback regarding beta-carotene deficiency facilitates rapid and appropriate optimization of beta-carotene supplementation in feed.
The term proteinuria is taken to mean abnormally high protein excretion in the urine. Proteinuria is the consequence of glomerular filtration of plasma proteins, their subsequent reabsorption by the proximal tubular cells and secretion of protein by the tubular cells and distal urinary tract. In physiological conditions, the structural integry of the glomerular filtration barrier prevents the abnormal passage of albumin (molecular mass 66 kDa) and high-molecular- weight proteins (> 66 kDa),whereas the passage of low-molecular-weight proteins (< 66 kDa) is almost completely unrestricted. Proteins that arrive the tubular lumen are reabsorbed by endocytosis after binding to the megalin-cubilin complex. An increased load of proteins in the tubular lumen leads to the saturation of the reabsorptive mechanism and higher urinary protein excretion. Proteinuria can originate from prerenal, renal and postrenal causes. Elevated tubular protein concentrations have been recognized to be toxic to tubular cells and associated with the progression of chronic renal disease. Therefore, the quantitative and qualitative evaluation of proteinuria is important for the diagnosis of renal disease