Reproductive Performance of Sows Supplemented with Dietary L-carnitine over Three Reproductive Cycles

The effect of L-carnitine supplementation during pregnancy and lactation on the reproductive performance of sows was studied in two separate trials over three reproductive cycles. Both trials were identical in design and conduct but were performed with different animals. The trials comprised of a total of 127 sows (trial 1) and 100 sows (trial 2) which were divided into control and treatment groups. All animals were fed individually and received basic feed mixtures with low native carnitine concentrations. The rations of the sows in the treated group were supplemented with 125mg L-carnitine per head and day during pregnancy and 250mg L-carnitine per head and day during lactation. The animals of the control group received identical feed mixtures in identical amounts, but without the L-carnitine supplement. In the first trial, 212 litters were produced and evaluated for number and body weight of the animals, in the second trial, 173 litters were produced. L-carnitine supplementation significantly increased body weight gains of the sows between day 1 and day 85 of weaning. The number of born piglets, stillborn piglets and piglets fit for rearing was not influenced by dietary L-carnitine supplementation. However, L-carnitine supplementation significantly increased the weights of piglets and litters at birth, weight gains of litters during suckling and weights of litters at weaning. These effects of L-carnitine were seen in both trials; they were independent of the age of the sows and remained over three reproductive cycles in which the sows where continuously treated with L-carnitine. Overall, the study shows that dietary supplementation with L-carnitine during pregnancy and lactation improves the reproductive performance of sows over several reproductive cycles, independent of the age of the sows.     

Effect of dietary calcium on cadmium absorption and retention in suckling rats

The effect of calcium supplementation on absorption and retention of cadmium in the suckling period was evaluated in Wistar rat pups of both sexes. Animals were maintained in the litters with the mother rats and supplemented with 1%, 3% or 6% calcium (as CaHPO₄×2H₂O) in cow's milk by artificial feeding from day of birth 6 through 14. All rats were exposed to cadmium (as CdCl₂×H₂O) either orally or parenterally. Oral cadmium dose of 0.5 mg/kg body weight a day was administered through nine-day period of calcium supplementation and parenteral cadmium dose was injected subcutaneously in a single dose of 0.5 mg Cd/kg body weight prior to calcium supplementation. On experimental day 10 (at the age of pups of 15 days) all animals were killed and the liver, kidneys, brain and carcass (body without organs and skin) were removed for element analyses. Cadmium and essential elements calcium, zinc and iron were analysed in the tissues by atomic absorption spectrometry. Results showed that after oral exposure cadmium concentrations in all calcium-supplemented groups were significantly decreased in the organs and carcass and that the effect was dose-related. No such effect of calcium was found after parenteral cadmium exposure. Calcium supplementation per se significantly increased calcium concentration in the carcass and had no effect on iron in organs and zinc in carcass. It was concluded that calcium supplementation during the suckling period could be an efficient way of reducing oral cadmium absorption and retention without affecting tissue essential trace element concentrations.     

Effects of vitamin E and carotenoid status on oxidative stress in health and disease. Evidence obtained from human intervention studies

Vitamin E and carotenoids are known to act as antioxidants both in vitro and in vivo. In this review we present a series of studies in healthy subjects and in patients who exhibit either acute or chronic oxidative stress. In the EU-Commission funded VITAGE project we investigated the status and effects of vitamin E and carotenoids on oxidative stress in 300 healthy volunteers. Depletion studies limiting dietary vitamin E or carotenoid intake to 25% of the dietary reference intakes and subsequent repletion by supplementation with either large doses of vitamin E or intermediate doses of carotenoids showed significant changes in ex vivo LDL oxidizability, total plasma peroxide concentrations and urinary 8-oxo-7,8-dihydro-2^′-deoxyguanosine excretion. Patients on chronic hemodialysis present with oxidative stress in the presence of normal vitamin E but impaired vitamin C status and, due to anemia, need to be treated with parenteral iron. We studied the effects of a single oral dose of vitamin E taken 6 h prior to intravenous infusion of 100 mg iron, which exceeded the iron-binding capacity of transferrin. Vitamin E significantly reduced and in combination with a single dose of vitamin C completely abrogated acute oxidative stress induced by the iron load. Patients with cystic fibrosis are exposed to chronic oxidative stress due to an overproduction of reactive oxygen species as a result of neutrophil-dominated lung inflammation and impaired antioxidant status. Biochemical vitamin E and carotenoid deficiencies could be fully corrected even in the presence of fat malabsorption using intermediate doses of either RRR -tocopherol or all-rac -tocopheryl acetate and water-miscible all-trans β-carotene. Long-term supplementation reduced ex vivo LDL oxidizability, in vivo lipid peroxidation and lung inflammation.     

Iron Metabolism in the Anaemia of Chronic Renal Failure. Effects of Dialysis and of Pareuteral Iron

Serial studies of iron transport in patients on maintenance dialysis showed normal or raised values in almost all subjects and a transient increase soon after the start of dialysis in three. These patients, who were seldom or never transfused, had low serum iron levels and normal iron-binding capacity with low saturation. Iron transport was substantially increased by parenteral iron-dextran treatment. Tracer studies showed good iron utilization, with transport to the marrow rather than to the liver. In these circumstances iron therapy is safe and beneficial, and a useful rise in red cell mass was shown to result from it. The packed cell volume was found to be a valid index of red cell mass in these patients. Red cell loss in the dialysers was insufficient to account for the observed reduction in red cell survival.     

Maternal dietary supplementation with ferrous N-carbamylglycinate chelate affects sow reproductive performance and iron status of neonatal piglets

Iron-deficiency anemia is a public health concern that frequently occurs in pregnant mammals and neonatal offspring. Ferrous N-carbamylglycinate chelate (Fe-CGly) is a newly designed iron fortifier with proven effects in iron-deficient rats and weanling piglets. However, the effects of this new compound on pregnant mammals are unknown. Therefore, this experiment was conducted to evaluate the effects of Fe-CGly on sow reproductive performance and iron status of both sows and neonatal piglets. A total of 40 large-white sows after second parity were randomly assigned to two groups (n=20). They were receiving a diet including 80 mg Fe/kg as FeSO₄ or Fe-CGly, respectively, from day 85 of gestation to parturition. The serum (day 110 of pregnancy) and placentas of sows were sampled. Litter size, mean weight of live born piglets, birth (live) litter weight, number of live born piglets, and the number of still-born piglets, mummies, and weak-born piglets were recorded. Once delivered, eight litters were randomly selected from the 20 litters per treatment, and one new-born male piglet (1.503±0.142 kg) from each selected litter was slaughtered within 3 h after birth from the selected litters, without colostrum ingestion. The serum, longissimus muscle, liver and kidneys of the piglets were collected. The iron status of the serum samples and the messenger RNA level of iron-related genes in the placenta, liver and kidney were analyzed. The results showed that litter weight of live born piglets was higher (P=0.030) in the Fe-CGly group (19.86 kg) than in the FeSO₄ group (17.34 kg). Fe-CGly significantly increased placental iron concentration (P<0.05) of sows. It also significantly increased iron saturation and reduced the total iron-binding capacity of piglets (P<0.05) at birth. However, the results revealed that supplementation of Fe-CGly in sows reduced liver and kidney iron concentration of neonatal piglets (P<0.05), indicating decreased iron storage. In addition, the concentration of iron in the colostrum was not significantly changed. Therefore, the present results suggested that replacement of maternal FeSO₄ supplement with Fe-CGly in the late-gestating period for sows could improve litter birth weight, probably via enhanced iron transportation in the placenta.     

n-6 and n-3 fatty acids ratio and vitamin E in porcine maternal diet influence the antioxidant status and immune cell eicosanoid response in the progeny

Five groups of lactating sows were fed diets containing 8% of either added rapeseed oil, fish oil or sunflower oil and 60 mg vitamin E/kg feed, or the diets with sunflower oil and fish oil, respectively, supplemented with 500 mg vitamin E/kg. Supplementation of vitamin E to the sows increased the concentration of alpha-tocopherol of the muscle, and addition of sunflower oil decreased the activity of glutathione peroxidase in liver cytosol compared to fish oil and rapeseed oil. The composition of fatty acids of alveolar macrophages (AM) of piglets was influenced by the dietary fat sources provided the sows, i.e., the ratio of n-6:n-3 fatty acids was highest in AM of piglets suckling sows of the sunflower oil treatments, and lowest in AM of piglets suckling sows fed fish oil with the rapeseed oil treatment in between. The ex vivo synthesis of prostaglandin E(2) and thromboxane B(2) in AM of piglets suckling sows fed sunflower oil was elevated compared to piglets suckling sows fed fish oil. Vitamin E supplementation to sows enhanced the synthesis of these eicosanoids, and also the concentration of alpha-tocopherol in the AM of the piglets.     

水生植物修复铁污染水体的效果及作用机制

为解决铁离子污染导致水体发黄问题,采用水培试验,分析了水禾、粉绿狐尾藻、圆币草、黄花水龙、大薸和圆叶节节菜等6种水生植物对铁离子污染水体的修复能力,研究了铁离子浓度、pH和植物生物量对水禾修复效果的影响,并探讨了曝气对水禾除铁的强化作用。结果表明: 6种水生植物均不同程度地促进了水中二价铁和全铁的去除,不同植物对铁的去除效果差异显著;试验24 h,水禾和圆币草处理二价铁浓度分别由5.0 mg·L^-1降至0.23和0.26 mg·L^-1,满足《地表水环境质量标准》(GB 3838—2002)限值要求(二价铁浓度≤0.3 mg·L^-1),全铁浓度降至0.84和1.21 mg·L^-1,去除率达83.2%和75.8%。pH在5、6、7、8时,各pH处理组二价铁和全铁浓度无显著差异,二价铁和全铁去除率分别为95.4%～98.4%和92.2%～94.6%。二价铁初始浓度≤5.0 mg·L^-1时,二价铁和全铁去除率随二价铁浓度增加而增大;高浓度二价铁(10.0 mg·L^-1)对水禾生长有一定的抑制作用,试验期间全铁去除不稳定,试验结束时全铁去除率较对照仅提高7.0%,远低于其他浓度处理。生物量≥300 g时,处理24 h,二价铁浓度从5.0 mg·L^-1降至0.3 mg·L^-1以下,且各生物量处理去除效果差异不显著。间歇曝气和连续曝气均强化水禾对铁的去除,连续曝气更利于稳定去除全铁。     

Sex-related differences in hematological values. A study on the erythrocyte and granulocyte count, plasma iron and iron-binding proteins in human transsexuals on contrasexual hormone therapy

Hematological data known or supposed to be influenced by individual sex hormones were evaluated in 18 untreated transsexuals (TS) and in 20 castrated or non-castrated TS on androgen and estrogen treatment, respectively. Profiting from a situation of clinically controlled hormonal sex-transformation it was tested, whether the circulating erythrocyte and granulocyte mass and iron metabolism are linked to a male and female sex-hormone constellation. The erythrocyte and granulocyte counts were significantly higher in untreated males and treated female-to-male TS than in untreated females and treated male-to-female TS. The unexpected finding of sex hormone-dependent granulocyte fluctuations was corroborated by parallel concentration changes of lactoferrin, a granulocyte-derived plasma protein. Iron metabolism as judged from plasma iron, total iron-binding capacity and serum ferritin was unaffected by sexual transformation. Plasma iron and the total iron-binding capacity did not differ significantly in untreated and treated TS of either type. The serum ferritin concentration, however, was significantly lower in untreated as well as in virilized females than in untreated and in feminized males, but was not significantly changed by long-term androgen or estrogen treatment. The present study demonstrates the potential of human transsexualism as a model for the study of sex-related biological processes.     

Effects of prolonged iron loading in the rat using both parenteral and dietary routes.

Female Porton rats have been treated with either parenteral iron (intraperitoneal red cells) or dietary iron (carbonyl iron) for up to 12 months or 22 months respectively. In the parenteral iron loaded animals, the liver iron concentration rose from approximately 2 mg g^-1 dry wt at 2 months to 21 mg g^-1 dry wt at 12 months, while for the dietary iron loaded animals, this value rose from 14 to 48 mg g^-1 dry wt at 12 months to over 60 mg g^-1 dry wt after 22 months. In contrast, splenic iron concentrations rose more in the parenterally loaded animals (up to 66 mg g-1 dry wt after 12 months) than in the dietary loaded animals (approx. 34 mg g^-1 dry wt after 24 months). This study yielded hepatic iron concentrations comparable to those seen in human thalassaemia patients with comparative low hepatotoxicity. Splenic iron concentrations in the parenteral iron loaded group generally exceeded those reported in thalassaemia. Iron concentrations derived from computer assisted morphometry of liver iron deposits correlated well ( r = 0.88, p < 0.001) with chemical analysis data. The fraction of iron in the non-parenchymal cells correlated positively with the duration of iron loading (r = 0.86, p < 0.001).     

Accumulation of storage iron in patients treated for iron-deficiency anaemia.

The repletion of iron stores after treatment was studied in 38 patients with uncomplicated iron-deficiency anaemia. The serum ferritin concentration rose significantly when oral treatment was continued for two months after the attainment of a normal haemoglobin concentration. Patients treated with a total-dose infusion of iron dextran had thehighest final serum levels, which were significantly greater than in patients given Ferro-Gradumet. Oral ferrous sulphate was almost as effective as parenteral iron in producing iron stores.     

A newly identified iron-binding protein in rat liver: purification and characterization

A novel iron-binding protein from rat liver homogenates was purified 1,800-fold with a 5.7% yield, to apparent homogeneity. The molecular weight of the protein was estimated to be 16,000, by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The purified protein exhibited 0.43 mol of iron binding per mol of protein with a dissociation constant (Kd) of 3.5 x 10(-6) M. Al3+ inhibited the iron-binding and the binding was also slightly inhibited by Ni2+. Other divalent metal ions such as Cu2+, Zn2+ and Mn2+ were without effect. Immunoblot analysis of the iron-binding protein revealed that the protein is located mainly in microsomes. This newly identified iron-binding protein may be involved in intracellular transport of iron.     

Iron dextran treatment does not induce serum protein carbonyls in the newborn pig

Oxidation of serum proteins can lead to carbonyl formation that alters their function and is often associated with stress-related diseases. As it is recommended that all pigs reared in modern production facilities be given supplemental iron at birth to prevent anemia, and metals can catalyze the carbonylation of proteins, the primary objective of this study was to determine whether standard iron dextran treatment was associated with enhanced serum protein oxidation in newborn piglets. Piglets were treated with 100 mg of iron dextran intramuscularly either on the day of birth, or on the third day after birth. Blood samples were collected from piglets 48 or 96 h after treatment and serum was harvested. For quantification, serum protein carbonyls were converted to hydrazones with dinitrophenyl hydrazine and analyzed spectrophotometrically. To identify and determine relative distribution of carbonylated proteins, serum protein carbonyls were derivatized with biotin hydrazide, separated by two-dimensional polyacrylamide gel electrophoresis, stained with avidin-fluorescein and identified by mass spectrometry. The standard iron dextran treatment was associated with no increase in total oxidized proteins if given either on the first or third day of life. In addition, with a few noted exceptions, the overall distribution and identification of oxidized proteins were similar between control and iron dextran-treated pigs. These results indicate that while iron dextran treatment is associated with a marked increase in circulating iron, it does not appear to specifically induce the oxidation of serum proteins.     

Plasma relaxin levels during suckling and oxytocin stimulation in the lactating sow

Plasma relaxin levels were measured in animals at different stages of lactation and related to the amount of nuzzling and suckling behavior exhibited by the piglets. Only in some acute suckling episodes was relaxin secreted rapidly and episodically in spite of normal piglet and sow behavior and interaction. However, when the piglets were removed from the dams 6 h before suckling, the sows were very restless and the relaxin response to suckling was delayed. Oxytocin injection in lactating but nonsuckled sows caused an episodic secretion of relaxin similar to suckling itself. The source of relaxin in the lactating sow may be the old corpus luteum, since progesterone levels increased acutely, somewhat reflecting the profile of relaxin increase over the suckling episode.     

Piglets' weaning behavioural response is influenced by quality of human-animal interactions during suckling

The aim of this study was to compare the short-term post-weaning behaviour of piglets treated either neutrally or aversively during the suckling period. A total of 24 lactating sows and their litters were housed in different rooms according to treatment. A female experimenter (P1) was in charge of feeding and cleaning from days 10 to 27 after birth. For the aversive treatment (Aver), P1 was noisy, moved harshly and unpredictably and shouted frequently during routine cleaning of facilities and animal handling. For the neutral treatment (Neut), P1 used a soft tone of voice and was careful during the same routine. At weaning, the avoidance response of piglets to an approaching experimenter in a novel place was assessed in four piglets from each litter. Scores ranged from 1 (experimenter could touch piglet) to 4 (piglet escaped as soon as person moved). The test was repeated twice, with a 1-h interval, with P1, who wore blue trousers and white T-shirt, and a second handler unfamiliar to the piglets (P2, who wore blue coveralls). Thereafter, litters from the same treatment were mixed and housed in separate rooms, balanced for gender and live weight (n = 12 groups of 4 piglets/treatment). Behaviour time budgets were registered by scan sampling every 2-min, for 4 h per day, for 4 days. Piglets were weighed at birth, at weaning and on day 5. Effects of treatment and handler on responses to the avoidance test were analysed with non-parametric tests and effects of treatment with a mixed model for repeated measures. Avoidance score was higher for Aver than Neut piglets when tested with P1 (P = 0.04) but not with P2 (P = 0.8). When piglets' responses to the different handlers were compared within each treatment, no significant differences were found. Frequencies of resting were lower (P < 0.001), whereas escape attempts (P < 0.03), agonistic interactions (P < 0.02) and frequency of presence at feeder (P < 0.001) were higher in the Aver than in the Neut groups. Feed and water intake and weight gain did not differ between treatments. We conclude that 4-week-old piglets can discriminate a handler according to the nature of treatment received during suckling. In addition, piglets treated aversively seem to have more difficulty adapting to weaning than those treated neutrally during the suckling period.     

Plasma ferritin and other parameters related to iron metabolism in piglets

The evolution of mean plasma ferritin values, hematocrit, hemoglobin, plasma iron concentration and total plasma iron binding capacity were studied during the growth of piglets from 0 to 50 days. The results obtained point to a massive mobilization of iron from storage sites during the second and third weeks of life of these animals. Apart from plasma ferritin values and the total plasma iron binding capacity, the coefficient of utilization may be considered as another parameter to be taken into account upon evaluating iron deposits in piglets.     

Iron-binding antioxidant capacity is impaired in diabetes mellitus

Increased lipid peroxidation contributes to diabetic complications and redox-active iron is known to play an important role in catalyzing peroxidation reactions. We aimed to investigate if diabetes affects the capacity of plasma to protect against iron-driven lipid peroxidation and to identify underlying factors. Glycemic control, serum iron, proteins involved in iron homeostasis, plasma iron-binding antioxidant capacity in a liposomal model, and non-transferrin-bound iron were measured in 40 type 1 and 67 type 2 diabetic patients compared to 100 nondiabetic healthy control subjects. Iron-binding antioxidant capacity was significantly lower in the plasma of diabetic subjects (83 +/- 6 and 84 +/- 5% in type 1 and type 2 diabetes versus 88 +/- 6% in control subjects, p < 0.0005). The contribution of transferrin, ceruloplasmin, and albumin concentrations to the iron-binding antioxidant capacity was lost in diabetes (explaining only 4.2 and 6.3% of the variance in type 1 and type 2 diabetes versus 13.9% in control subjects). This observation could not be explained by differences in Tf glycation, lipid, or inflammatory status and was not associated with higher non-transferrin-bound iron levels. Iron-binding antioxidant capacity is decreased in diabetes mellitus.     

Effect of tocilizumab on haematological markers implicates interleukin-6 signalling in the anaemia of rheumatoid arthritis

Introduction

Our objective was to determine the interrelationships of interleukin (IL)-6 receptor inhibition with haemoglobin, acute-phase reactants and iron metabolism markers (including hepcidin) in patients with rheumatoid arthritis (RA).

Methods

Data of patients receiving tocilizumab or placebo in the MEASURE study were analysed. We investigated associations at baseline and during tocilizumab treatment among haemoglobin, parameters of haemoglobin and iron homeostasis [ferritin, total iron-binding capacity (TIBC), hepcidin, haptoglobin], IL-6 and acute-phase reactants [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] to identify statistical correlates of rise in haemoglobin level.

Results

At baseline, CRP and haptoglobin were inversely correlated (modestly) with haemoglobin levels. After treatment with tocilizumab, CRP, hepcidin, ferritin and haptoglobin levels fell alongside increases in TIBC and haemoglobin. The falls in CRP, hepcidin and haptoglobin levels in the first 2 weeks correlated with a week 12 rise in TIBC and haemoglobin.

Conclusions

Inflammatory anaemia improves in patients with RA treated with tocilizumab. This improvement correlates with the degree of suppression of systemic inflammation, reduction in hepcidin and haptoglobin and increase in iron-binding capacity. These clinical data provide evidence of a role for IL-6 signalling in the inflammatory anaemia of RA.     

Haematinic effect of Hygrophila spinosa T. Anderson on experimental rodents

Ethanolic extract of the aerial parts of H. spinosa a semiwoody herb was examined on male albino rats for certain haematological changes. The extract (100 & 200 mg/kg, po) significantly increased the haemoglobin, haematocrit, RBC and total WBC, as compared with vehicle treated control rat haemogram. In anemic male albino rats, the extract significantly increased haemoglobin, haematocrit and RBC count. Serum iron and serum total iron binding capacity were significantly decreased in H. spinosa extract treated anemic rats as compared with those in the vehicle treated anemic control rats. These findings demonstrated the haematinic effect of H. spinosa extract on experimental animals.     

Hydroxamic acid-containing hydrogels for nonabsorbed iron chelation therapy: synthesis, characterization, and biological evaluation

Iron overload is a severe clinical condition and can be largely prevented by the use of iron-specific chelating agents. A successful iron chelator needs to be orally active, nontoxic, and selective. In this study, hydrogels containing pendant hydroxamic acid groups have been synthesized as potential nonabsorbed chelators for iron in the gastrointestinal tract. The synthetic method employed to introduce hydroxamic acid groups to polymer chains involved reaction of polymer gels based on N-acryloxysuccinimide, acryloyl chloride, and (2-hydroxyethyl)acrylate monomers with hydroxylamine. These hydroxamic acid-functionalized polymer gels swell favorably in water and effectively sequester iron. In vitro iron-binding properties of these hydrogels were evaluated from their binding isotherms by use of iron(II) alone and in the presence of other competing metal ions. These polymers bind iron over a broad pH range. The iron-binding properties of the polymers were found to depend on the concentration of hydroxamate groups on polymer chains. The in vivo iron-binding efficacy of the polymers was evaluated in rat as the animal model. The polymers prevented an increase in serum hemoglobin and hematocrit levels in the animals, thus suggesting the prevention of systemic absorption of dietary iron from the gastrointestinal tract. The animals also maintained normal body weight during the treatment period, indicating the absence of any apparent toxicity associated with these polymers.