Trace metal biochemistry : Influence of intravenous infusion of a multielement mixture

Trace element biochemistry following a multielement intravenous infusion in man was studied. A new trace-element additive mixture was prepared by Kabi-Vitrum, Sweden (code 4854). to meet the requirements of moderately ill patients. This mixture provided a daily supply of Fe 20 mumol (1.12 mg); Mn 100 mumol (6.54 mg); Cu 20 mumol (1.27 mg); Mn 15 mumol (0.82 mg); Cr 0.4 mumol (20.8 pg); Se 0.4 mumol (31.58 ug); Mo 0.2 mumol (19.19 ug); I 1.0 mumol (0.13 mg); F 50 mumol (0.95 mg). To evaluate the efficacy of this mixture in meeting the trace-element requirements in patients, three different studies were undertaken. Serum and urine samples were collected with precautions to avoid contamination. Levels of zinc, copper, manganese, chromium and selenium, in serum and urine were determined by proven atomic absorption techniques. Results were compared statistically within and between the groups and to appropriate reference values. This thesis deals with the determination of zinc, copper, manganese, chromium and selenium in serum and urine. Methods for Mo, I and F were not readily available. Studies were as follows: Crystalloid Study: In this study, twenty patients undergoing elective abdominal surgery were randomly allocated into two groups. Group A received saline and glucose (5%) only for four post-operative days. Group B received an additional daily infusion of trace-element mixture (code 4854). , In Group A serum zinc fell sharply, but returned to normal by day five. Serum copper, manganese, chromium and selenium were unchanged and urinary excretions did not alter. In Group B, serum zinc followed the same pattern as Group A, but serum copper and selenium were mostly unaffected. Serum and urinary chromium and manganese were markedly increased during infusion, whereas urinary zinc, copper and selenium were not significantly increased. Surgical I.V.N.: In this study, sixteen patients undergoing elective surgery were studied for more than seven days. They received 14 g N and 3000 KCal/day (2000 KCal as glucose, and 1000 KCal as Intralipid) and trace element additive mixture. These patients were divided into two groups. Group A as anabolic patients with urine N less than 12 g/day. Group B as catabolic patients with urine N greater than 14 g/day. In both groups, serum values of zinc, copper and selenium remained normal, while manganese and chromium increased. Urinary excretion of copper was unaffected, while that of zinc, manganese, chromium and selenium was increased. Medical I.V.N.: Four patients were studied for more than fourteen days. The infusion regimen was similar to that used in surgical IVN. Serum zinc and copper were maintained during infusion and manganese and chromium were elevated, while selenium was at the lower level of normal range. Urinary excretion was increased for chromium, zinc and manganese, while copper and selenium were unaffected. The supplement of zinc and copper was sufficient to correct any pre-existing abnormality and to maintain most of the patients. However, for patients with excessive intestinal fluid loss higher amounts may be desirable. The provision of manganese and chromium may have been excessive, only half of the amount provided may be enough for most patients. No clinical or biochemical abnormality suggestive of deficiency or toxicity for any of the infused elements was found

Ethnic differences in parathyroid hormone secretion and mineral metabolism in response to oral phosphate administration

Ethnic differences in bone metabolism have been reported and it has been suggested that these may be partly due to prolonged exposure to an elevated plasma parathyroid hormone (PTH) concentration or a decreased sensitivity to PTH. We explored ethnic differences in bone and mineral metabolism by 5 days of oral phosphate (P) loading to stimulate PTH secretion. Healthy older people from UK (B), The Gambia (G) and China (C), 15 individuals from each sex and ethnic group, were studied. Blood and urine samples were collected before and 2 h after P dose on days 1, 4 and 5 and on a control day. The induced changes (%) in PTH and markers of mineral and bone metabolism after 2 h and over 5 days were examined. At baseline, PTH, 1,25(OH)2D and bone turnover markers were higher in Gambian subjects than in British and Chinese subjects (P ≤ 0.01). 2 h after P loading, ionized calcium (iCa) decreased and PTH and plasma P (P) increased in all groups (P ≤ 0.01, n.s. between groups). Urinary P to creatinine ratio (uP/Cr) increased, the increase being greater in Chinese subjects than in British and Gambian subjects on days 4 and 5 (P ≤ 0.01). By day 5, fasting iCa was decreased and P increased in British and Gambian (P ≤ 0.01) but not in Chinese subjects. Fasting PTH and uP/Cr increased in all groups. There were ethnic differences in changes in bone markers, but the relationship with changes in PTH was comparable between groups. In conclusion, ethnic differences in mineral metabolism in response to 5-day P loading were found. Chinese subjects showed a more rapid renal clearance of P than British and Gambian counterparts and there were differences between the groups in the skeletal response to P loading, but no evidence was found for resistance to the resorbing effects of PTH

Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

Peer reviewedPublisher PD

The aetiology of rickets-like lower limb deformities in Malawian children

Summary: Debilitating rickets-like lower limb deformities are common in children throughout the world, particularly in Malawi, Africa where the causes are unknown. We have identified that Blount disease and calcium deficiency rickets are the likely causes of these deformities and propose calcium supplementation as a potential treatment of Malawian rickets. Introduction: Surgical correction of rickets-like lower limb deformities is the most common paediatric operation performed at Beit Cure Orthopaedic Hospital, Malawi. The aim of this study was to investigate the aetiology of these deformities. Methods: Children with a tibio-femoral angle of deformity >20° were enrolled (n = 42, 3.0–15.0 years). Anthropometric and early life and well-being data were collected. Early morning serum and urine samples were collected on the morning of the operation for markers of calcium and phosphate homeostasis. Knee radiographs were obtained, and the children were diagnosed with either Blount (BD, n = 22) or evidence of rickets disease (RD, n = 20). As BD is a mechanical rather than metabolic disease, BD were assumed to be biochemically representative of the local population and thus used as a local reference for RD. Results: There were no differences in anthropometry or early life experiences between BD and RD. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, total alkaline phosphatase and urinary phosphate were significantly higher and serum phosphate, 25-hydroxyvitamin D (25OHD) and tubular maximal reabsorption of phosphate significantly lower in RD than BD. There was no difference in serum calcium, fibroblast growth factor 23 or markers of iron status between groups. All children had 25OHD > 25 nmol/L. Conclusions: Vitamin D deficiency is not implicated in the aetiology of RD or BD in Malawian children. The cause of RD in Malawi is likely to be dietary calcium deficiency leading to elevated PTH resulting in increased losses of phosphate from the bone and glomerular filtrate. The causes of BD remain unclear; there was no evidence in support of previously suggested risk factors such as being overweight or starting to walk early. Prior to surgical intervention, supplementation with calcium should be considered for children with RD

Single and repeated moderate consumption of native or dealcoholized red wine show different effects on antioxidant parameters in blood and DNA strand breaks in peripheral leukocytes in healthy volunteers: a randomized controlled trial [ISRCTN68505294]

BACKGROUND: Red wine (RW) is rich in antioxidant polyphenols that might protect from oxidative stress related diseases, such as cardiovascular disease and cancer. Antioxidant effects after single ingestion of RW or dealcoholized RW (DRW) have been observed in several studies, but results after regular consumption are contradictory. Thus, we examined if single or repeated consumption of moderate amounts of RW or DRW exert antioxidant activity in vivo. METHODS: Total phenolic content and concentration of other antioxidants in plasma/serum, total antioxidant capacity (TEAC) in plasma as well as DNA strand breaks in peripheral leukocytes were measured in healthy non-smokers A) before, 90 and 360 min after ingestion of one glass of RW, DRW or water; B) before and after consumption of one glass of RW or DRW daily for 6 weeks. DNA strand breaks (SB) were determined by single cell gel electrophoresis (Comet Assay) in untreated cells and after induction of oxidative stress ex vivo with H(2)O(2 )(300 μM, 20 min). RESULTS: Both RW and DRW transiently increased total phenolic content in plasma after single consumption, but only RW lead to a sustained increase if consumed regularly. Plasma antioxidant capacity was not affected by single or regular consumption of RW or DRW. Effects of RW and DRW on DNA SB were conflicting. DNA strand breaks in untreated cells increased after a single dose of RW and DRW, whereas H(2)O(2 )induced SB were reduced after DRW. In contrast, regular RW consumption reduced SB in untreated cells but did not affect H(2)O(2 )induced SB. CONCLUSION: The results suggest that consumption of both RW and DRW leads to an accumulation of phenolic compounds in plasma without increasing plasma antioxidant capacity. Red wine and DRW seem to affect the occurrence of DNA strand breaks, but this cannot be referred to antioxidant effects

The antioxidant activities of phenolic compounds in wine and related foods Effect on human plasma and low density lipoproteins

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN024551 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

The Antioxidant Activites of Phenolic Compounds in Wine and Related Foods: Effect on Human Plasma and Low Density Lipoproteins.

The oxidation of low density lipoprotein (LDL) is one mechanism by which serum cholesterol may deposit in the arterial wall causing coronary heart disease (CHD). Epidemiological studies have provided evidence to suggest an inverse relationship between the dietary intake of flavonoids and the risk of CHD. Of the many groups of flavonoids present in foods, chiefly in vegetables, fruit, tea and wine, the polyphenols are especially important since they have been shown to express potent antioxidant activities in vitro. They are particularly abundant in red wine, a high consumption of which has been implicated in the low mortality from CHD in countries such as France, giving rise to the ‘French paradox’. Despite intense interest in the potential health benefits of dietary polyphenols, the outcome of studies addressing this issue have been largely inconclusive. The overall aim of this study was to determine whether the putatively protective effects of red wine are mediated through an in vivo antioxidant action of extracted red wine polyphenols and related foods and whether alcohol affects their biological activity. The initial objective of this study was to develop methods for assessing the oxidative status of plasma and oxidative susceptibility of LDL. Once established, these assays were used to test a range of different polyphenols for their antioxidant potential in vitro for a human ‘intervention trial’. The selected polyphenol supplements were then used as dietary supplements in a 2 week dietary intervention in healthy male volunteers. Measures of oxidation status and polyphenol content in plasma and LDL were determined before and after dietary supplementation. Supplementation with red wine and extracted red wine polyphenols either alone or in combination with white wine, alcohol, or vitamin E was associated with a significant increase in total antioxidant status of plasma and decrease in the oxidative susceptibility of LDL and lipid peroxides. It was also shown to increase the polyphenol content of plasma and LDL, and total plasma TGF-β levels. From these data it can be concluded that the polyphenols contained within red wine and similar beverages are powerful inhibitors of LDL oxidation and that alcohol promotes pro-oxidation changes in these parameters

Pregnancy supplementation of Gambian mothers with calcium carbonate alters mid-childhood IGF1 in a sex-specific manner

Context: sex-specific effects of pregnancy calcium carbonate supplementation have been reported in 8�12�year old Gambian children, indicating faster growth in boys but slower growth in girls born to calcium-supplemented mothers.Objective: to determine whether the pregnancy supplement resulted in sex-specific effects on offspring IGF1 and other growth-related indices in mid-childhood.Design: analysis of archived data obtained in mid-childhood from the children of rural Gambian mothers who had been randomised to 1500�mgCa/d (Ca) or placebo (P) from 20�weeks pregnancy to delivery (ISRCTN96502494).Participants and methods: of the 526 children born and followed in infancy, 290 had early-morning, fasting plasma assayed for IGF1, IGFBP3, leptin, insulin and calcium-related indices and had anthropometry performed at age 7.5 (SD1.2) years (N/group: Males(M)-Ca�=�64, Females(F)-Ca�=�77; M-P�=�76, F-P�=�73). Sex-specific effects of maternal supplementation were considered using regression with sexes separated and together to test for sex���supplement interactions.Results: boys had lower IGF1, IGFBP3, leptin and insulin than girls (P���0.004). IGF1 was higher in M-Ca than M-P (+14.2 (SE7.7)%, P�=�0.05) but lower in F-Ca than F-P (�17.8 (SE7.4)%, P�=�0.01); sex���supplement interaction P�=�0.001. IGF1 concentrations (ng/ml, geometric mean [�1SE,+1SE]) were M-Ca�=�78.1[4.3,4.5], M-P�=�67.8[3.4,3.6]; F-Ca�=�99.5[4.8,5.1], F-P�=�118.9[6.4,6.8]. Similar sex���supplement interactions were seen for IGFBP3 and IGF1-adjusted-for-IGFBP3 but group differences were smaller. There were no significant supplement effects on the other biochemical indices.Conclusions: calcium carbonate supplementation of pregnant Gambian mothers resulted in higher IGF1 in boys and lower IGF1 in girls during mid-childhood, consistent with the reported maternal supplement effects on growth of the offspring in later childhood

Interrelation of parathyroid hormone and vitamin D metabolites in adolescents from the UK and The Gambia

Parathyroid hormone (PTH) is used as a marker of vitamin D (VD) status. However, PTH depends on many other factors. The 24,25-dihydroxy VD (24,25VD) concentration may be a sensitive marker because its production is reduced in VD deficiency. The relationship between VD metabolites, their ratio and PTH was investigated in adolescents from the UK and The Gambia with different calcium intakes and VD status. In the UK, there was a significant positive (+ve) association between 25VD and both 1,25-dihydroxy VD (1,25VD) and 24,25VD and a negative (−ve) association with PTH. The 24,25:25VD ratio was consistent across the 25VD concentration range. There was a +ve association between PTH and 1,25:25VD, (1,25 + 24,25):25VD or 1,25:24,25VD, a −ve association with 24,25VD and none with 1,25VD or 24,25:25VD. Using LnPTH and 1,25:25VD ratio (but not 1,25VD:24,25VD or 25VD:24,25VD) increased uniformity between groups and strength of relationships compared to PTH and 1,25 or 25VD alone. In The Gambia, there was a significant −ve relationship between 25VD and PTH and none with 1,25VD. There was a +ve association between 1,25VD or 1,25:25VD and PTH. The more uniform prediction of PTH by the 1,25VD:25VD ratio may be because this better reflects the extent to which PTH-induced 1,25VD production can be met by VD supply. Further validation is needed

Increased Plasma Concentrations of Vitamin D Metabolites and Vitamin D Binding Protein in Women Using Hormonal Contraceptives: A Cross-Sectional Study

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