Role of Complements C3 and C5 in the Phagocytosis of Liposomes by Human Neutrophils

During the course of a previous investigation, we noticed that the uptake of liposomes by human polymorphonuclear neutrophils (PMNs) was significantly lower in the presence of heat-inactivated serum compared to that in intact whole serum (Scieszka et al., Pharm. Res. 5:352, 1988). This observation suggested the participation of heat-labile complement components in the phagocytic process. In this report we conclude that complement C3bi is the component responsible for opsonization of the liposome surface. Phagocytosis was not supported by C3-deficient serum, and phagocytosis in whole serum was blocked by the antibody to the receptor for C3bi (CR3) but not by the antibody to the receptor for C3b (CR1). We also found that with C5-deflcient serum the level of uptake was minimal but slightly higher than without any serum. When exogenous C5a was added along with C5-deficient serum, uptake levels similar in magnitude to those observed with intact serum were obtained. We conclude that C5a enhances phagocytosis of opsonized liposomes by activating the phagocytic capacity of CR3 on the PMN.     

Cellular Uptake of a Fluid-Phase Marker by Human Neutrophils from Solutions and Liposomes

In assessing the feasibility of utilizing the phagocytic activity of polymorphonuclear leukocytes (PMNs) for a more efficient drug delivery to the cell, the uptake of the fluid-phase marker lucifer yellow CH (LY) at 37°C by human PMNs from LY-containing liposomes was compared with that from solutions. In the presence of 10% autologous serum, the LY uptake at 37°C via phagocytosis of LY-containing liposomes was generally two orders of magnitude greater than that via pinocytosis for a given PMN source when the concentrations of PMN, LY, and total lipid were in the range of 10⁷ cells/ml, 0.5 mg/ml, and 50 µmol/ml, respectively. As expected, the LY uptake via phagocytosis was critically dependent upon the LY entrapment efficiency in the liposome preparation. Interestingly, little LY uptake was found when the serum was heat inactivated (56°C × 30 min). The serum effect was upon liposome vesicles rather than upon the cells. The present study demonstrates that the use of particular drug carriers for targeted drug delivery to PMNs and possibly to an extravascular site mediated by the cell infiltration is a viable approach.     

Caffeine (1,3,7-trimethylxanthine), a temperate promoter of DMBA-induced rat mammary gland carcinogenesis

The administration of caffeine to the drinking water (250 mg/l and 500 mg/l) of female Sprague-Dawley rats after treatment with 7,12-dimethylbenzanthracene (DMBA) (5 mg i.g.) resulted in an increase in mammary carcinoma incidence. The confidence levels of statistical significance for the groups of rats receiving the 250-mg and 500-mg doses of caffeine were >0.70 and >0.99, respectively. This increase in mammary carcinoma incidence was observed when caffeine treatment was initiated commencing 3 days after DMBA treatment and continued for 21 weeks. This effect was also observed when caffeine treatment was initiated commencing 20 weeks after DMBA treatment and continued for 6 weeks in rats relatively refractory to carcinogen treatment (mammary tumor-free at onset of treatment) and in rats relatively sensitive to the carcinogen (mammary tumor bearing at onset of caffeine treatment). Caffeine treatment of rats prior to and during carcinogen treatment did not significantly affect mammary carcinoma incidence. Thus caffeine consumption has been shown to significantly enhance the promoting phase but is without effect on the initiating phase of this carcinogenic process.     

Anti-inflammatory and monocyte-suppressing effects of simvastatin in patients with impaired fasting glucose

The aim of our study was to compare the effect of simvastatin on systemic inflammation and monocyte secretory function between individuals with impaired fasting glucose (IFG) and patients with isolated hypercholesterolaemia. The study included 25 patients with IFG and 23 patients with hypercholesterolaemia. The lipid profile, fasting and 2-hr post-glucose load plasma glucose levels, homeostatic model assessment (HOMA) ratio, glycated haemoglobin, plasma high-sensitivity C-reactive protein (hsCRP) levels and monocyte release of TNF-α, interleukin-1β, interleukin-6 and MCP-1 were assessed at baseline, and after 30 and 90 days of simvastatin treatment (20 mg/daily). Compared to monocytes of the control patients (22 age-, sex- and weight-matched patients without lipid and glucose metabolism abnormalities), monocytes of the patients with hypercholesterolaemia and patients with IFG released greater amounts of all studied cytokines and exhibited higher plasma levels of hsCRP, with no difference between the two groups of patients. Although in both the patients with hypercholesterolaemia and the patients with IFG simvastatin treatment improved lipid profile, it exhibited no effect on glucose metabolism markers. The drug markedly reduced plasma hsCRP and monocyte secretion of TNF-α, interleukin-1β, interleukin-6 and MCP-1 in a lipid- and glucose-independent manner. Our results indicate that low-grade systemic inflammation and monocyte secretory function are disturbed to a similar degree in the patients with isolated hypercholesterolaemia and in the patients with IFG. They also show that simvastatin is an effective anti-inflammatory drug in patients with isolated early glucose metabolism abnormalities.     

The use of high-frequency jet-ventilation in operative bronchoscopy

The authors report on the use of HFJV in operative laser fibre-optic bronchoscopy, especially in combination with the laser technique. The method and initial results are discussed. Also high-risk patients can be treated with this method without the need for general anaesthesia.     

Selected acute phase proteins and interleukin-6 in systemic lupus erythematosus patients treated with low doses of quinagolide

The relationship between endocrine regulation and immune system has recently become the subject of intense investigations. The objective of this study was to determine the extent of selected serum acute phase proteins (APP), IL-6 and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) involvement in systemic lupus erythematosus (SLE) patients during quinagolide therapy. A further aim of this study was to evaluate the relationships between the above mentioned parameters. In 25 SLE patients treated with a low dose of quinagolide (12.5-50 microg per day) and in 25 healthy persons who constituted the control group, serum concentration of C-creative protein (CRP), alpha-1-antitripsin (AAT), ceruloplasmin (CER), IL-6 and prolactin (PRL) were estimated at entry and in patients after 3 months of treatment. Moreover, SLEDAI score was calculated at entry and after 3 months of therapy with quinagolide. IL-6 and PRL levels were significantly higher in SLE group whereas the concentrations of CRP, AAT and CER were higher than in the controls, but without statistical significance. After 3 month therapy statistically significant decrease of serum level of IL-6 and PRL was revealed. Statistically significant lower serum concentration of CER was also obtained after 3 months of therapy whereas serum CRP and AAT concentration was lower compared with the mean pretreatment level but the results did not reach statistical significance. A raised SLEDAI score at entry was significantly reduced after 3 month therapy and positive correlation with PRL level in examined group of patients with SLE was noted at entry. The decreased serum concentration of IL-6, APP and SLEDAI score observed during applied therapy with small dose of quinagolide confirms the hypothesis that quinagolide may become a valuable and safe drug in the therapy of patients with mild SLE.     

Quality of life in cancer patients treated by chemotherapy

Many studies connected with different aspects of the quality of life (QL) have been increasingly reported. In this study we have been used FACT questionnaire to estimate QL in three groups of cancer patients receiving chemotherapy. Questionnaires were completed by 177 patients. Adverse effects of treatment severely influence the cancer patients QL. The most significant worsening of QL was noticed in the group of lung cancer patients receiving the most emetogenic chemotherapy(i.e. cis-platinum, vepesid). In other two groups (gastric and colorectal cancer patients) side effects of chemotherapy caused relatively less QL deterioration. This finding implicates possibility of intensifying the course of treatment (dosage and duration) assuming there is no hematopoetic insufficiency.