M. Leclercq

Occurrence of β2-microglobulin and post-γ globulin in human semen

Abstract The authors have studied the protein fraction of seminal fluid in the zone 10 000–20 000 daltons. The presence of two proteins was noted: β2-Microglobulin and post-γ globulin, characteristic of low molecular weight proteins in urine.

Is vitamin K1 supplementation necessary in long-term parenteral nutrition?

BACKGROUND I.v. lipid emulsions contain vitamin K in substantial quantities and in 1989, we therfore stopped supplying vitamin K1 to patients receiving home parenteral nutrition (HPN). METHODS Nine patients (group I) receiving HPN before 1989 (10 mg i.v. vitamin K1 supplementation weekly until 1989, which was discontinued thereafter) and six patients with an initial low plasma vitamin K1 concentration (related to their malabsorption) (group II) receiving HPN after 1989 were studied. Prothrombin time (PT), plasma vitamin K1 concentration, and vitamin K1, content in lipid emulsions were measured throughout the period of HPN. RESULTS All lipid emulsions, except for Eurolip 20% and Clinoleic 20% (Baxter SA, Maurepas, France) contained vitamin K1, with concentration ranges from 179 +/- 39 to 353 +/- 78 ng/L. Group I patients had an initial high plasma vitamin K1 concentration due to the vitamin K1 supplementation. After this supplementation was discontinued, plasma vitamin K1 decreased and remained in normal ranges with a normal PT. Throughout the HPN period after 1989, patients received 255 +/- 104 micrograms of vitamin K1 weekly through lipid emulsions. The PT and plasma vitamin K1 concentrations in group II patients were restored by lipid emulsions, which contained 418 +/- 143 micrograms/wk of vitamin K1. CONCLUSIONS In patients receiving i.v. lipids (except for Eurolip and Clinoleic), a normal vitamin K1 status can be maintained during long-term HPN without vitamin K1 supplementation. However, vitamin K supplementation cannot be abandoned until the vitamin K content of emulsions is standardized by manufacturers. A weekly supply of 250 to 400 micrograms of vitamin K1 is enough to maintain and even restore a normal vitamin K1 status in HPN.

Skin disorders and vitamin A metabolism disturbances in chronic dialysis patients: the role of zinc, retinol-binding protein, retinol and retinoic acid

The authors have studied--in the plasma--the changes of zinc, retinol binding protein (RBP), retinol and retinoic acid with reference to the dermatological status of fifty chronically haemodialysed renal insufficiency patients divided into four subgroups (normal skin, dry skin, dry skin with keratosis, and only keratosis). The results of these groups were compared to those of thirty healthy subjects. The values of these variables do not show any significant difference in function of the dermatological subgroups; but, despite the considerable rise in the retinol binding protein and retinol levels in comparison with the controls (haemodialysis patients: RBP = 11.77 +/- 2.83 mumol X l(-1), retinol = 7 +/- 2.57 mumol X l(-1); controls; RBP = 2.76 +/- 0.62 mumol X l(-1), retinol = 2.16 +/- 0.53 mumol X l(-1] the electromicroscopic examination of skin biopsy samples from some of the patients did not reveal any sign of hypervitaminosis A in the lesions.

Specificity of increased des-gamma-carboxyprothrombin in hepatocellular carcinoma after vitamin K1 injection

The des-gamma-carboxyprothrombin (DCP) level was found to be increased in the majority of hepatocellular carcinomas (HCC). This increase has to be distinguished from an increased DCP level linked to a vitamin K deficiency. We studied the evolution of increased DCP level in 6 patients with histologically proven HCC and in 10 without HCC after slow injection of 20 mg of vitamin K1. The DCP assays performed subsequent to the vitamin K1 injection showed: first, a durable normalisation of the DCP level in the patients without HCC, suggesting that the increased DCP was linked, in them, to an underlying vitamin K deficiency; second, a transitory decrease followed by a return to the abnormal level in the patients with HCC. We can conclude that an increased DCP level which persists following vitamin K1 injection is specific for HCC. The minimal delay for the DCP assay after vitamin K1 injection seems to be 15 days.

An unknown source of vitamin K1 in patients on total parenteral nutrition

We found a level of 20.8 +/- 3.4 mug/dl of vitamin K1 (VK1) in Intralipid 20% and initiated a study based on the follow-up of children receiving total parenteral nutrition without any other exogenous VK1 intake than from Intralipid 20% (1 g/kg/day). This lipid administration was sufficient to cover the needs during a study period of 4 to 29 weeks.

Serum vitamin K1 concentration and vitamin K-dependent clotting factor activity in maternal and fetal cord blood

The serum concentration of phylloquinone (vitamin K1) was measured in 34 healthy mothers and in the arterial cord blood of their newborn infants. In addition, the activities of factor II and of factors VII plus X were determined simultaneously in 16 paired maternal and fetal bloods. The serum vitamin K1 concentration was similar to that of control subjects in 27 mothers: 9.03 +/- 4.9 micrograms/L (mean and SD), with a simultaneous concentration of 10.4 +/- 5.3 micrograms/L in cord blood. Six mothers exhibited high serum vitamin K1 concentrations from 40 to 240 micrograms/L (median, 82) and the concentration in cord blood ranged from 25 to 115 micrograms/L (median, 71). One mother had a normal concentration of vitamin K1: 9 micrograms/L while no vitamin K1 was detectable in the serum of her infant. The activity of factor II and factors VII plus X was 7% and 7%, respectively, in this infant and 100% in the mother. All other mothers showed normal factor II and factors VII plus X activity, while the median activity was 47% (28%-56%) for factor II and 65% (35%-100%) for factors VII plus X in cord blood. These data suggest that vitamin K1 can cross the placental barrier but not in every case. Therefore the systematic administration of vitamin K1 to the newborn infant seems to be required to prevent the occurrence of the hemorrhagic disease.

Vitamin K1 diffusion across the placental barrier in the gravid female rat.

The hemorrhagic disease of the newborn can be prevented by administration of vitamin K1. The modes of utilization of the vitamin need to be studied in the mother and child. An experimental pharmacokinetic study was conducted, using the gravid female rat. Results showed rapid intestinal absorption of phylloquinone. The fetus plasma concentration rose from 8.6 micrograms/l at time 0 to 0 to 44.3 micrograms/l at 8 h. Such an increase is an evidence of phylloquinone diffusion across the placenta. The phenomenon requires a high gradient. On the other hand, maximum plasma concentrations are not reached until the 8th hour.

γ-carboxyglutamic acid in urine of newborn infants

γ-Carboxyglutamic acid (GLA) was measured in the urines obtained from 11 full-term infants, 48 pre-term infants appropriate for gestational age (AGA), and 25 small-for-gestational age (SGA) infants. Separation was performed by high resolution anion exchange chromatography. The results were similar in both AGA and SGA infants. During the first 3 days of life, urinary GLA mean (and range) was 1.66 (0.34–4.60) in the low birth weight infants versus 0.88 (0.26–1.38) in the full-term infants and 0.76 (0.62–1.15) μmol · kg−1 · 24 h−1 in the control adults. In the low birth weight infants, urinary GLA fell from 2.79 (0.61–5.75) at age 1–3 days, to 1.55 (0.26–4.04) μmol/24 h at day 8 (p < 0.01); it then rose again slowly to 2.12 (0.65–3.93) μmol/24 h at day 45. In these infants there was no correlation between urinary GLA excretion and birth weight or gestational age, or urinary hydroxyproline or serum alkaline phosphatase. Despite the well-known reduced blood levels of vitamin K dependent coagulation factors in neonates, these results show that urinary GLA excretion is at least similar to the excretion in adults. These data suggest that these neonates can carboxylate glutamic acid and that the newborn infant has a high bone turnover.

The use of preparative continuous flow electrophoresis to study low molecular weight proteins in urine

The authors propose a convenient method for the separation of low molecular weight proteins, present in tubular urines. In particular, the method is used for the purification of beta2 microglobulin, after one recycling, and also for the isolation of the various post-gamma globulins which can later be separated on DEAE Sephadex.