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Nous avons mesure les concentrations de carnitine totale, de carnitine libre et d'acylcarnitine sur le sang, le plasma et les erythrocytes de 88 femmes pendant la grossesse. D'une facon generale, a la 12 e semaine de la grossesse, le taux moyen de carnitine sanguine a ete nettement plus bas (p < 0,01) que sur les sujets temoins. A partir de la 12 e semaine de grossesse et jusqu'a l'accouchement, nous avons releve une baisse significative (p < 0,01). Cette diminution de la carnitine totale dans le sang total est provoquee generalement par une baisse nette (p < 0,01) du taux de carnitine libre alors que nous n'avons pas note de modifications prononcees des valeurs des chaines courtes de l'acylcarnitine pendant toute la grossesse. L'apport de la L-carnitine des erythrocytes a la carnitine du sang total a progresse nettement (p < 0,05) pour atteindre 61% a l'accouchement contre 39% chez les temoins. Sur le sang du cordon ombilical, les taux de camitine libre et de carnitine total etaient nettement plus eleves (p < 0,05) que les taux maternels correspondants. L'apport de la L-carnitine des erythrocytes a l'ensemble de la camitine du sang total etait plus eleve dans le sang du cordon que dans le sang maternel. Chez les omnivores, la synthese de L-carnitine intervient pour le huitieme a la moitie de la carnitine disponible dans l'organisme. Nous savons maintenant que la biosynthese endogene a elle seule ne suffit pas pour porter le taux de L-carnitine a un niveau suffisant. La biosynthese de la carnitine est desormais bien connue. La premiere etape est constituee par la methylation des residus de lysine des proteines specifiques donnant la trimethyllysine. La biosynthese de la trimethyllysine est controlee par reconstitution de la proteine, l'hypothese etantque la lysine libre n'est pas methylee chez l'homme. En consequence, il n'y a pas d'interaction entre l'accroissement des pertes renales de carnitine et le taux de la synthese de carnitine. En conditions normales, la concentration de carnitine dans le plasma est reglee partiellement par la cinetique de la reabsorption de L-carnitine par les reins. Plus de 90% de la L-carnitine filtree est reabsorbee. Bien que le taux de L-carnitine soit bas pendant la grossesse, la clairance renale de l'acylcarnitine est nettement plus elevee que chez les sujets non enceintes. En consequence, la diminution de la carnitine du plasma ne provoque pas de demande durant les premieres semaines de la grossesse. La carnitine facilite donc le rejet des cellules des groupes acyles excedentaires et potentiellement toxiques, qui sont rejetees avec l'urine sous forme d'acylcarnitine. Il est possible que les besoins de carnitine augmentent pendant la grossesse pour pouvoir realiser cette fonction metabolique. Les resultats de la presente etude etablissent que pendant la grossesse, les taux de carnitine su sang total et du plasma diminuent pour atteindre ceux des sujets souffrant de deficience de carnitine. Les taux d'acylcarnitine dans la camitine totale etablis par la presente etude sont eux aussi typiques d'un deficit de carnitine secondaire. En consequence, la substitution de L-carnitine peut etre avantageuse, tout specialement dans les grossesses a risque.

Patients on chronic hemodialysis with hyperlipidemia were found to respond either with decreased levels (responders) or with a further increase of the plasma triglyceride levels (nonresponders) to a c

Anemia and carnitine supplementation in hemodialyzed patients. Carnitine supplementation in hemodialyzed patients was studied in a double-blinded, randomized, controlled trial in order to elucidate the effect of intravenous carnitine on renal anemia in patients treated with recombinant human erythro-poietin (rHuEPO).Twenty stable hemodialysis (HD) patients received intravenous L-carnitine after each dialysis session in a dosage of 5 (N = 15) and 25 (N = 5) mg/kg, respectively, together with intravenous iron saccharate (20 mg/HD session) for four months and without iron for a further four months. Twenty patients received placebo instead of carnitine with an identical iron regimen. After a run-in phase of six months with a stable rHuEPO requirement, the rHuEPO dose was adjusted monthly when necessary to maintain target hemoglobin levels. At study entry (T0), plasma and red blood cell carnitine levels did not correlate significantly with the rHuEPO requirement. However, plasma free and total carnitine levels showed a significant negative correlation with erythrocyte survival time at T0. After four months of coadministration of intravenous iron and L-carnitine (T4), the rHuEPO requirement decreased in 8 of 19 evaluable HD patients. In these responders, the weekly rHuEPO dose was decreased significantly by 36.9 ± 23.3% (183.7 ± 131.7 at T0 vs. 126.6 ± 127.9 U/kg/week at T4, P < 0.001). The rHuEPO requirement, however, was unchanged when all carnitine-treated patients were compared between T0 and T4 (T0: 172.0 ± 118.0 vs. T4: 152.3 ± 118.8 U/kg/week, P = 0.07, NS), but the erythropoietin resistance index decreased significantly in this group (T0: 16.0 ± 11.0 vs. T4: 13.6 ± 10.5 U/kg/week/g of hemoglobin, P < 0.02).The erythrocyte survival time was measured in five HD patients treated with iron and carnitine at T0 and T4. Two out of these patients were carnitine responders and showed an increase of erythrocyte survival time of 15 and 20%, respectively.After the withdrawal of iron supplementation, the rHuEPO requirement increased comparably in both L-carnitine- and placebo-treated patients during four more months.According to our data, L-carnitine, in addition to iron supplementation, may have an effect on erythropoietin resistance and erythrocyte survival time in HD patients. More than half of our patients, however, showed no benefit. Further studies to identify those HD patients who might have a benefit of carni-tine supplementation, as well as studies concerning the optimal dosage, duration, and way of administration of carnitine supplementation and its mechanism of action, are required.

Serum and urinary neopterin concentrations were measured in 142 patients suffering from various malignant diseases. Increased serum and urinary neopterin levels were found in 48% and 55% of patients respectively. Neopterin showed sufficient sensitivity in the detection of haematological disorders and hypernephroma, whereas the sensitivity of neopterin was rather poor in patients with other solid tumours. Comparison of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) concentrations and serum or urinary neopterin levels in testicular cancer patients showed that determination of neopterin provides no further information in the management of these patients. In testicular cancer patients receiving adjuvant chemotherapy, a significant increase in serum (p less than 0.005) and urinary (p less than 0.0005) neopterin concentrations was measured after chemotherapy, reflecting the release of neopterin from macrophages during the damage by cytotoxic drugs. In the adjuvant testicular tumour patients, known to be tumour free, 1 out of 16 patients showed elevated serum and 3 out of 15 patients showed false positive urinary neopterin levels. False positive serum (24%) and urinary (37%) neopterin values were also obtained in 28 patients with various nonmalignant diseases, but no evidence for an inflammatory process. In 23 patients with inflammatory diseases pathological serum and urinary neopterin levels were measured in 55% and 59% respectively. When a RIA was compared with a HPLC method, higher urinary neopterin values were obtained with the RIA, indicating that non-oxidized pterines are also determined by the RIA method. In conclusion, neopterin might be a helpful biological marker in monitoring patients with malignant haematological disorders and renal cell carcinoma, but provides no additional information in other solid tumours studied.