Pulmonary surfactant in bronchoalveolar lavage after canine lung transplantation: effect of L-carnitine application.

Pulmonary surfactant during lung transplantation was investigated in the control group of a canine single lung transplantation model by measuring dipalmitoyl-phosphatidylcholine, the main phosphocholine fraction of surfactant in bronchoalveolar lavage. In a second group of dogs, L-carnitine, an essential cofactor for transfer of long-chain fatty acids into the mitochondria, was applied. Organ function after pulmonary artery flushing with modified Euro-Collins solution and hypothermic storage for 4 hours was adequate in both groups, with significantly higher arterial oxygen pressure levels in the L-carnitine group after 12 (p less than 0.05) and 24 (p less than 0.025) hours, respectively. In the control group, a reduction of the dipalmitoyl-phosphotidylcholine portion on total phosphotidylcholines was observed 4 and 12 hours after transplantation of the left lung (p less than 0.005 and p less than 0.01, respectively, both specified by Student's t test for dependent data, not significant by Bonferroni correction). In the simultaneously stored right lungs, a constant fall of the dipalmitoyl-phosphotidylcholine portion was demonstrated. In the L-carnitine group, significantly higher dipalmitoyl-phosphotidylcholine levels were observed in the transplanted left lungs after 4 hours (p less than 0.01) and in the continuously stored right lungs after 24 hours (p less than 0.005), when compared with the control group. These results suggest that dipalmitoyl-phosphotidylcholine portion on total phosphotidylcholine decreases parallel to the extent of the ischemic damage. Furthermore, the application of L-carnitine improved pulmonary function after transplantation, possibly by reducing the impairing effect of ischemia on alveolar type II cell metabolism and thereby on pulmonary surfactant system.

Changes in essential fatty acids in plasma lipid fractions of polytraumatized patients with different parenteral nutrition.

We investigated changes in the fatty acid pattern of plasma lipids during the phase of total parenteral nutrition in two groups of polytraumatized patients. For parenteral nutrition we gave L-amino acid solutions in a dose of 0.24 g N day-1kg-1 body weight. In addition, we administered in the first group glucose and fructose, and in the second group glucose, fructose and fat emulsions in a total dose of 30 kcal day-1kg-1 body weight. In the latter group, the proportion of the fat emulsions was 30-40% of the calories administered. The most striking findings were the decrease of the essential fatty acids with regard to the phospholipid fraction from about 60% to 30% in the early post-traumatic phase. In the first group of patients we observed a further reduction of the essential fatty acids in the period of observation. This could be avoided by administering fat emulsions of the same type as we gave in the second group of patients. The functions of essential fatty acids in membranes and in the intermediary metabolism are discussed.

Changes in essential fatty acids in plasma lipid fractions of traumatized patients.

Changes in the fatty acid pattern of plasma lipid in four different groups of polytraumatized patients were investigated. All of the patients received amino acid solutions containing 0.24 gN/day/kg body weight and 30 kal/day/kg body weight (BW). In group 1, all calories were administered as carbohydrates (glucose and fructose). In group 2, 30 to 40% of the calories were provided as a fat emulsion. When compared to the control group, a reduction in the essential fatty acid concentration in the phospholipid fraction was detected in both groups during the early post-traumatic period. In group 1, a continuous decline was observed during the remainder of the trial period. In group 2, however, the concentration of essential fatty acids remained constant after the initial decline and increased slightly from the 7th day on. In the second part of the investigation, the effect of human growth hormone (HGH) administration on the fatty acid pattern was evaluated. Group 3 and 4 received intravenous feedings identical to the patients in group 2; in group 4, however, 10 mg of HGH per day were added to the infusion. The results of this study confirm the hypothesis that supplemental infusion of a fat emulsion prevents a continuous reduction of essential fatty acids in plasma lipids. An effect of 10 mg/day of HGH on essential fatty acid concentration or composition, however, could not be observed. There were no detectable differences in the percentage of essential fatty acids between those patients receiving and those not receiving HGH.

Chelidonium majus L. (Ukrain) in the treatment of cancer patients.

Ukrain, a semi-synthetic thiophosphoric acid compound of alkaloid chelidonine isolated from Chelidonium Majus L., Tris(2-([5bS-(5ba,6b,12ba)]-5b,6,7,12b,13,14- Hexahydro-13-methyl][1,3]-benzodioxolo[5,6-c]-1,3-dioxolo[4, 5- i]phenanthridinium-6-ol]-Ethaneaminyl) Phosphinesulfide 6HCl, causes a regression of tumours and metastases in many oncological patients. More than 400 documented patients with various carcinomas in different stages of development have been treated with Ukrain. The authors report on only three different cases treated with preparation Ukrain. Ukrain can be helpful in improving the general condition and prolonging life by reduction of the tumour progression and its immunomodulating effect on the organism.

Combined therapy with Ukrain and chemotherapy in ovarian cancer (case report).

A patient with adenocarcinoma in the right ovary with lymphangitis carcinomatosa, staged as G II-G III pT3, pNX, pMX, was treated after palliative surgery by chemotherapy and, simultaneously, with Ukrain. Two and a half years after treatment the patient is without any signs of tumour recurrence. Her condition is excellent.

[Animal experiment and clinical studies of the significance of carnitine for energy metabolism in pregnant patients and the fetus during the pre- and perinatal period]. / Tierexperimentelle und klinische Untersuchungen über die Bedeutung des Carnitins für den Stoffwechsel der Schwangeren und des Feten während der Prä- und Perinatalperiode.

Carnitine was discovered at the beginning of this century, but was nearly forgotten until its importance in fatty acid metabolism was established 50 years later. In the past years, several other functions of carnitine in cellular metabolism have been described. The lung contains more than 40 different cell types, most of them involved in lipid metabolism. Pulmonary surfactant, a complex of 90% lipids and 10% lung specific apoproteins, is synthesized and secreated from type II cells. Surfactant is present as a monolayer at the air-liquid interface in the alveoli and decreases surface tension. Dipalmitoyl phosphatidylcholine (DPPC) is functionally and quantitatively the most important constituent of the surfactant complex. A deficiency in fetal lung surfactant is the primary cause of the respiratory distress syndrome (RDS), the most severe complication of preterm infants. Glucocorticoids are frequently used to accelerate fetal pulmonary maturation. However, a considerable number of infants fail to respond to this therapy. Maternal administration of L-carnitine significantly increased the DPPC content of fetal rat lungs. The effect of maternal treatment with a carnitine-betamethasone combination was synergistic, especially with lower betamethasone doses. Consequently the minimal dose of betamethasone which affects the DPPC content and accelerate the morphological maturation of the fetal lung was determined. This minimal dose in combination with L-carnitine increased the DPPC content on day 19 of gestation to levels found on the 20th gestational day which allows the survival of most of the preterm rats (term 22 days). Results of clinical trials show that antenatal treatment with a low dose betamethasone-L-carnitine combination has a clear advantage over standard betamethasone therapy. A multicenter study is in progress. Plasma carnitine levels at delivery are decreased to about half of the concentrations seen in non-pregnant women. Similar low levels are found only in patients with carnitine deficiency. Already in the 12th week of gestation the mean whole blood and plasma carnitine levels were found to be significantly lower than those of controls. The reason for increased excretion of acylcarnitines during pregnancy is not known, but could be a detoxifying function similar to that found in patients with inborn errors of fatty acid metabolism and organic acidurias. Carnitine substitution (1 g daily) from the 20th gestational week up to parturition resulted in an increase of free carnitine levels in maternal plasma. A dosage of 0.5 g/day was without effect. Prolonged substitution in pregnant women, especially in risk pregnancies may be preferable to high doses of carnitine administered shortly before imminent premature delivery.

[lst report: Alternatives to cortisone therapy. lst clinical experiences with a carnitine-betamethasone combination for the stimulation of fetal lung maturity]. / Erste Mitteilung: Alternativen zur Cortisontherapie. Erste klinische Erfahrungen mit einer Carnitin-Betamethason-Kombination zur Stimulation der fetalen Lungenreife.

In the recent past criticism has been voiced with regard to the efficacy and possible side effects of corticosteroid prophylaxis of fetal respiratory distress syndrome (RDS). Apparently the efficacy of this treatment has been over-estimated and the spectrum of possible side effects has not received enough critical attention. In view of the multiple indications that the fetal metabolism, above all, may be altered by this type of therapy, it seems necessary to search for other methods of surfactant stimulation. This paper presents the first clinical study on the use of carnitine (4 g for 5 days in combination with twice 8 mg beta-methasone versus twice 8 mg betamethasone alone). The patients on combination therapy showed a more marked increase in surfactant content of the amniotic fluid. Lung compliance determination in infants born within 72 hours of completion of therapy also revealed better results in the combination therapy group. There were also fewer clinically demonstrable RDS cases in this group. More research will be necessary to definitely establish the value of this new form of therapy.