Ascorbic acid enhances hydroxyl radical formation in iron-fortified infant cereals and infant formulas

Infant cereals and formulas are usually fortified with iron to prevent iron deficiency. To enhance iron bioavailability, supplemental ascorbic acid is recommended. Ascorbic acid is considered to be an antioxidant in vivo, but has pro-oxidant effects when exposed to non-protein-bound iron. We measured formation of free radicals in cereals and infant formulas after addition of ascorbic acid. The production of hydroxyl radicals was assessed by hydroxylation of salicylic acid to 2,5-dihydroxybenzoic acid (2,5-DHBA). Production of 2,5-DHBA increased with increasing ascorbic acid doses added. Addition of 0.8 mM ascorbic acid to breast milk produced less radicals (0.03 ± 0.05 μM) than addition of ascorbic acid to low-iron formula (0.13 ± 0.08 μM, P = 0.019), medium-iron formula (0.34 ± 0.12 μM, P < 0.0001) or high-iron formula (0.44 ± 0.08 μM, P < 0.0001). Even when iron content in breast milk was adjusted to a level comparable with that of formulas, production of 2,5-DHBA was lower. Breast milk seems to contain substances that reduce hydroxyl radical formation. Conclusion Supplemental ascorbic acid causes hydro-xyl radical formation in iron-fortified infant nutrients in vitro. Received: 30 March 1996 / Accepted in revised form: 10 December 1996     

Alpha-1-antitrypsin levels and clinical symptoms in forty-eight children with selective IgA deficiency

Previous studies in adult patients with selective IgA deficiency have pointed towards a possible connection between chombined IgA and alpha-1-antitrypsin deficiency and the development of bronchiectasis. Thus, investigation were conducted of serum alpha-1-antitrypsin levels and clinical symptoms in 48 children with selective IgA deficiency. However, alpha-1-antitrypsin deficiency was not found in this group of patients. Furthermore, radiographic signs of recurrent pneumonia restricted to certain fields of the lungs, suggestive of bronchiectasia, were not observed in the patients. Thus, although a highly selected group of children with selective IgA deficiency was studied, a connection between IgA deficiency and alpha-1-antitrypsin deficiency as not obvious.Abbreviations RAST radio-allergo-sorbent-test - AAT alpha-1-antitrypsin     

Physiologically based pharmacokinetic model for pralmorelin hydrochloride in rats.

Pralmorelin hydrochloride (pralmorelin), consisting of six amino acid residues, is a growth hormone-releasing peptide. The aim of this study is to analyze the pharmacokinetics of pralmorelin after intravenous bolus administration to rats, and to develop a physiologically based pharmacokinetic (PB-PK) model to describe and predict the concentrations of pralmorelin in blood and tissues. Pralmorelin (3 mg/kg) was administered intravenously to 24 Sprague-Dawley rats. Groups of three rats were sacrificed by decapitation at each designated time point (up to 4 h), and plasma and tissues (brain, lung, heart, liver, kidney, small intestine, muscle, adipose, and skin) were collected. Bile was also pooled until decapitation. The concentration of pralmorelin in samples was determined by liquid chromatography-tandem mass spectrometry. Plasma concentrations of pralmorelin declined rapidly in a biexponential manner. Biliary excretion of pralmorelin was so rapid that 80% of the dose was recovered unchanged in the bile within 1 h after administration. The distribution parameters in each tissue were obtained by using a hybrid model and an integration plot. They revealed that the distribution of pralmorelin into liver was blood flow-limited, and its distribution was permeability-limited in all other tissues. The PB-PK model developed in this study well described the time courses of pralmorelin concentration in the blood and tissues of rats.     

Long-term trial of 1-alpha-hydroxycholecalciferol in adults with chronic renal failure

Summary Twentytwo adult patients with chronic renal insufficiency received long-term treatment (mean 15.4 months) with 1-alpha-hydroxycholecalciferol (1(OH)D₃), a synthetic vitamin D analogue. Before treatment 73% of the patients were hypocalcemic, intestinal calcium absorption was reduced in 82%, serum immunoreactive parathyroid hormone (i-PTH) was increased in 86% and serum alkaline phosphatases were increased in 50% of them. Furthermore, 91% of the patients had generalized scintigraphic bone changes indicative of renal osteodystrophy, 59% had reduced bone mineral content (BMC), 32% had radiographic bone changes and 27% had clinical symptoms. During treatment all patients became normocalcemic within one month; intestinal calcium absorption increased to reach normal values; i-PTH declined significantly, but remained elevated in 50% of patients; serum alkaline phosphatases declined significantly and became normal in all except 2 patients; bone scintigraphy and/or radiography showed considerable improvement in 4 patients; the accelerated bone loss in uremia ceased and bone pain disappeared in 5 of the 6 patients who had had this symptom. Nineteen short-lasting acute hypercalcemic episodes were recorded during treatment. In all cases normocalcemia was re-established within 72 hours after discontinuing the drug. No side-effects were observed apart from hypercalcemia. The present data demonstrate the long-term beneficial effects of 1 (OH)D₃ in improving clinical symptoms and reversing several biochemical and skeletal abnormalities in patients with chronic renal failure.     

Endocarditis due toKingella kingae

Four cases of endocarditis due toKingella kingae are described in compromised patients. All had primary heart disease, and two had systemic lupus erythematosis and congenital heart defect respectively, in addition. Confirmation ofKingella kingae was made in one case at autopsy. The literature on 11 cases of endocarditis, 2 bacteremia, 4 osteomyelitis, 5 septic arthritis and 1 intervertebral disc infection, all caused byKingella kingae, is reviewed. Our findings confirm that the organism is of low pathogenicity. Children may be predisposed to infection withKingella kingae.     

Fluid balance in exercise dehydration and rehydration with different glucose-electrolyte drinks

Summary After exercise dehydration (3% of body weight) the restoration of water and electrolyte balance was followed in 6 male subjects. During a 2 h rest period after exercise, a drink of one of four solutions was given as 9×300 ml portions at 15 min intervals: control (C-drink), high potassium (K-drink), high sodium (Na-drink) or high sugar (S-drink). An exercise test (submaximal and supramaximal work) was performed before dehydration and after rehydration. Dehydration reduced plasma volume by 16%, a process reversed on resting even before fluid ingestion began, due to release of water accumulated in the muscles during exercise. After 2 h rehydration, plasma volume was above the initial resting value with all 4 drinks. The final plasma volumes after the Na-drink (+14%) and C-drink (+9%) were significantly higher than after the K- and S-drinks. The Na-drink favoured filling of the extracellular compartment, whereas the K- and S-drinks favoured intracellular rehydration. In spite of the higher than normal plasma volume after rehydration, mean heart rate during the submaximal test was 10 bpm higher after rest and rehydration than in the initial test, and was not different between the drinks. The amount of work which could be performed in the supramaximal test (105% ) was 20% less after exercise dehydration and subsequent rest and rehydration than before. This reduction was similar for all drinks, and may be due to a decreased muscle glycogen content (70% of initial) at the time of the second test. Danish National Institute of Occupational Health     

The primary structure and specificity determining residues displayed by recombinant salmon antibody domains

Previously, single chain fragments of salmon (Salmo salar L.) immunoglobulin variable regions (scFv) were isolated by reactivity towards trinitrophenyl (TNP) or fluorescein (FITC) using phage display technology. The fine specificity of six scFv clones were analysed by ELISA, while the primary structure was determined by DNA sequencing. In addition, preliminary models of one anti-TNP and one anti-FITC clone were built. Here, a follow-up analysis of the primary and tertiary structure of all six clones is focused on the structural basis for hapten specificity. Tertiary structure was analysed by molecular modelling of the antigen combining site. The analysis shows that reactivity to each hapten is maintained by a number of different combinations of VH, D, JH and VL sequences. Accordingly, various sizes of CDR3 on both the heavy and light chain and CDR2 of IgH may support TNP binding. Due to variability of the antigen combining site each clone probably has a distinct binding affinity. However, a feature common among the four scFv antibodies that recognise TNP is a positively charged Arg in CDR2 of either the heavy or light chain. In the majority of the anti-TNP clones localisation of this side-chain is stabilised by a negatively charged Asp in LCDR1. In addition, a Trp in LCDR3 is conserved in all the anti-TNP clones. Also, the anti-FITC clones display a Trp in the LCDR3, suggesting its participation in binding of FITC as well. In combination with a large aromatic amino acid near the N-terminus of HCDR2 and a positively charged Arg in CDR1, these residues probably determine both specificity and affinity towards the FITC moiety.     

Electromyographic analysis of the knee during jump landing in male and female athletes

Many noncontact anterior cruciate ligament (ACL) injuries in female athletes occur at foot strike during jump landing when the knee is extended. This study was undertaken to determine the activation level of the quadriceps and hamstring muscles electromyographically. Fifteen healthy volunteers (eight women and seven men), all of whom were collegiate basketball players, participated in the study. The maximum voluntary contraction (MVC) of the vastus medialis (VM) at a knee flexion angle of 15-45 degrees was significantly higher in women than in men. There was no significant difference in overall mean hamstring activity in men and women over the same knee flexion range. However, when the knee flexion angle was 15 degrees , 20 degrees , and 25 degrees , hamstring activity was significantly lower in female athletes. These results suggest that female athletes have a higher risk of ACL injury during jump landing due to increased anterior tibial translation force with quadriceps muscle activity. Female athletes require greater hamstring activation, and it is suggested that exercising this muscle will increase its activity when the knee is extended, thus preventing ACL injury during actual sport motions.     

Evaluation of a multiplex PCR test for simultaneous identification and serotyping of Actinobacillus pleuropneumoniae serotypes 2, 5, and 6

Serotype-specific DNA regions involved in the biosynthesis of capsular polysaccharides (cps region) were used to develop a multiplex PCR test for the simultaneous species identification and serotyping of Actinobacillus pleuropneumoniae serotypes 2, 5, and 6. Primers specific for serotypes 2, 5, and 6 were combined with the already existing species-specific primers used in a PCR test based on the omlA gene. The PCR test was evaluated with serotype reference strains of A. pleuropneumoniae as well as 182 Danish field isolates previously serotyped by latex agglutination or immunodiffusion. For all serologically typeable strains, a complete correspondence was found between the results obtained by the multiplex PCR test and the results obtained by the traditional serotyping methods. Six of eight serologically nontypeable strains could be allocated to a serotype on the basis of the multiplex PCR results. The species specificity of the assay was evaluated with a collection of 93 strains representing 29 different species within the family Pasteurellaceae, as well as species normally found in the respiratory tracts of swine. All of these strains were negative by the multiplex PCR test, including 50 field isolates of the phylogenetically closely related species Actinobacillus lignieresii. When the multiplex PCR test was used to test Danish field strains, it was able to identify the serotypes of approximately 94% of all strains isolated from swine with clinical disease. More than 90% of the isolates that cross-reacted by the latex agglutination test were of serotype 2, 5, or 6. Determination of the serotype by PCR represents a convenient and specific method for the serotyping of A. pleuropneumoniae in diagnostic laboratories.