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THE INFLUENCE OF N-ACBTYLCYSTEINE ON CYSTEINE METABOLISM IN PRBTERM NEWBORN INFANTS Terhi Akola, Vine& FeZZmn, Risto Laptto, Knri 0. R&G, Hospital for Ckikfren and Adolescents, Hdsinki Uniwsity Cmhd Hospital, Uniwnity of Helsinki.

The svnthesls of elutathione, a major intracellular antioxidint, may n; be adequ&e in ireterm neonates because of the low levels of cystelne available. N-acetykystelne (NAC) is both a free radical s&venger and a precursorVfoicysteine. Mechanically ventilated newborn infants (BW 500-1380 g, GA 24-31 weeks) received an intravenous NAC infusion at a constant rate of 100 mg/kg/d for 24 h (n=lO, group A) or lo-24 mg/kg/d for 6 days(n=6, group 8). For both groups control infants were enrolled (n=8, BW=1030_1720g, GA=26-33weeks, and n=7, BW=705-1370g,GA=25_3lweeks). Total NAC and cyst(e)ine concentrations were measured during the first week of life from arterial dasma with an HPLC method with fluorometrlc det&ion. The median baseline cysteine concentration was 115 wol/L (range 50-190) with no intergroup difference. G group A th: plasma NAC increased up to the end of the infusion in 9 out of 10 infants, i.e. the steady-state was not fully reached. At the end of the infusion, the median plasma NAC was 480 pmol/l (range 380-T/0), and the cysteine was 58 pmol/L (range30-110). In.group B the steady-state of plasma NAC was reached in 5 of 6 patients within 50-70 h.On day 7. the median plasma concentration of NAC was 100 umol/L (ranee 60-410). and the cvsteine was 138 pmol/L (range 90-190). In 0% control group the fystelne concentration was 149 pmol/L (range 90-w)). Plasma cysteine concentrations were not significantly effected by NAC. . Nevertheless, the increased total thiol (NAC+Cys) levels ln the treatment group might have a positive effect on their antioxidant defence.

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Thiolactone Immunoassay for Total Plasma Homocysteine Eric Ferguson, Sampath Parthasarathy’, and B. Kalyanaraman Medical College of Wisconsin (MiIwaukee, Wr), ‘Emory University School of Medicine (Atlanta, GA)

Homocysteinemia is a well-recognized risk factor for the development many vascular disorders. The possibility that the newly discovered polyclonal antibody could be used in order to determine homocysteine concentrations by immunoassay has been investigated Homocysteine is coupled to a carrier molecule by the intermediate formation of homocysteine thiolactone and detected using a polyclonal antibody and ELISA. The rate o$HCl-mediated dehydration of homocysteine was monitored by the absorbance at 240 nm. In the presence of 6N HCI, at 25’C the kinetics of homocysteine thiolactone formation were slow, as efficient conversion did not occur until 12 hours. However, if the temperature was raised to 60’, efficient conversion occurred within 2 hours. Homocysteine thiolactone could be formed stoichiometrically in normal human plasma was spiked with homocysteine. Using the thiol-reactive nitroxide, MTSL, and the ESR spin labeling technique, it was demonstrated that homocysteine could be bound to BSA by the intermediate conversion to homocysteine thiolactone and acylation of BSA lysyl residues. In addition, using ELISA, homocysteine levels in normal human plasma that had been spiked with know concentrations of homocysteine were determined. Results indicate that the present methodology can analyze plasma samples in this manner, which may prove to be useful for routine analyses of plasma homocysteine.

GRAPE SEED PROANTHOCYANIDIN EXTRACT FOR THE TREATMENT OF CHRONIC PANCREATITIS Bkas+ ByGe, M.D., Ddykis fag&, Pk.D. Dept. of Mediciye, Uniarsity oJE~ssoY”, & Cmgkton UmmthJ Sckcvl of Pkannacy Profesmms, omdua,

Oxygen derived free radicals mediate tissue damage ln acute and chronic pancreatitls. Combination therapy with selenium, beta-carotene,methlonlne and vitamins C & E are known to improve symptoms but requires numerous tablets to be taken dally, which is impractical. We report the first successful use of Grape Seed Proanthocyanldin Extract (GSPE) in chronic pancreatltis. 1) A 39 year old man with a 3 year history of idiopathic relapsing pancreatitls had abdominal pain 4 - 5 times a month, each lasting 3 - 7 days and requiring narcotic analgesics. Pain was assessed as 5/10 on the Numerical Rating Scale (NRS). Symptoms and pancreatic inflammation persisted despite medical therapy.After starting GSPE 100 mg po tid, only a single episode of pain (5/1O,NRS) occurred in 7 months. 2) A 59 year old woman with chronic pancreatitls for 5 years had daily abdominal pain (7/1O,NRS) and vomiting despite pancreatic enzyme supplements and stent placement. Her pain improved (3/1O,NRS) on GSPE 100 mg tid with no more vomiting in the last 4 months. GSPE, a potent scavenger of free radicals, appears to provide effective symptom control in chronic pancreatitis. Prospective randomized studies need to be performed to assess the efficacy of GSPE in chronic pancreatitls.

TWO LEVELS 0.F IRON SU,eJ$EMENTATION AND DEVELOPMENTAL OUTCOME, IRON NUTRITION AND ADVERSE RESULTS IN LOW BIRTH WEIGHT INFANTS.

J. K. Friel. K Aziz, B. Simmons and W Andrews Depts of Biochem. & Pediatrics. Memorial Univ., St. John’s, NF., Canada

Conflicting opinions exist over the optimal amount of iron that low birth weight infants (LBW) should receive. To investigate the effect of increased iron intakes we randomly assigned infants at 2000 gms weight to receive either a formula with 12 mg iron/l (irotz) or 21 mg/L (hrgh iron) for a period of one year. At baseline, 3, 6, 9 and 12 months of age, the following measurements were completed: weight, RBC hemoglobin, catalase and superoxide dismutase (in progress); plasma malondialdehyde (MDA), ferritin, zinc and copper; and Grifflths Mental Development Scales (GMD). There were no differences at any time for weight, RBC hemoglobin and catalase, plasma ferritin or GMD. Plasma MDA at 9 months (High iron 1933 2 663. iron 1591+ 506. P=O 07), plasma zinc (High irm 71 + 13; IRON 94i 26) and plasma copper (iL_ligh iron 107 2 24; iron 13 1 2 29; P ~0.05) at 12 months indicated possible lipid peroxidation and inhibition of zinc and copper absorption with increased iron intake. There is no advantage to iron intakes above current recommendation for LBW infants. Supported by the Medical Research Council of Canada

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