Magnetic drug targeting--biodistribution of the magnetic carrier and the chemotherapeutic agent mitoxantrone after locoregional cancer treatment

Magnetic Drug Targeting means the specific delivery of chemotherapeutic agents to their desired targets, e.g. tumors, by using magnetic nanoparticles (ferrofluids) bound to these agents and an external magnetic field which is focused on the tumor. This type of target directed drug injection attempts to concentrate a pharmacologic agent by enhancing its efficacy while simultaneously minimizing deleterious side effects. In previous studies, we have been able to demonstrate the efficacy of this type of localized intraarterial chemotherapy in VX2 squamous cell carcinoma among rabbits [Alexiou, C., Arnold, W., Klein, R.J., Parak, F.G., Hulin, P., Bergemann, C., Erhardt, W., Wagenpfeil, S. and Lübbe, A.S. "Locoregional cancer treatment with Magnetic Drug Targeting", Cancer Res. 60 (2000) 6641-6648]. In the present investigation, we have studied the biodistribution of ferrofluids and chemotherapeutic agent by measuring the amount in the tumor, peritumoral area, various organs and body fluids (e.g. blood and urine), with and without Magnetic Drug Targeting. We compared results to that of administering a chemotherapeutic agent soley. An external magnetic field was directed toward the tumor for 60 min. Biodistribution of ferrofluids in the tumor was investigated using histological cross sections and measured semi-quantitatively using 123I-labeled nanoparticles and quantitatively by the use of radioactive 59Fe-ferrofluids. Mitoxantrone was quantitatively measured using HPLC-analysis. The strength of the external magnetic field was 0.6 Tesla (permanent magnet) in the 123iodine study and 1.7 Tesla (electromagnet) in the 59Fe-study and HPLC-analysis. The concentration of the ferrofluids (FFs) in the tumor region i.e. the tumor tissue and the surrounding area, which was under the influence of an external magnetic field, was found to be much higher than in the absence of one. In contrast to systemic chemotherapy, a much higher concentration of mitoxantrone in the tumor and the peritumoral area (region surrounding the tumor < or = 1 cm), by using only 50% and 20% of the normal dose was seen. Thus, the higher concentration of mitoxantrone could explain the therapeutic efficacy of Magnetic Drug Targeting in treatment of VX2 squamous cell carcinoma in rabbits in our previous studies with the advantage of no adverse clinical side effects.     

Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health

BACKGROUND: Fortification of milk with vitamin D may not be adequate for satisfying the vitamin D requirement because of variability in vitamin D content after fortification and because many persons have milk allergy or lactose intolerance. Additional foods need to be fortified with vitamin D. OBJECTIVE: We determined whether vitamin D, a fat-soluble vitamin, is bioavailable in orange juice and skim milk, 2 nonfat beverages. DESIGN: On 3 separate occasions, 18 adults ingested 25 000 IU vitamin D(2) in 240 mL whole milk or skim milk or in 0.1 mL corn oil applied to toast. A separate, double-blind, randomized, controlled trial investigated whether the consumption of orange juice fortified with vitamin D(3) would increase serum 25-hydroxyvitamin D [25(OH)D] concentrations: 14 subjects ingested 240 mL orange juice fortified with 1000 IU vitamin D, and 12 subjects ingested a control orange juice daily for 12 wk. RESULTS: Peak serum vitamin D(2) concentrations did not differ significantly after the ingestion of vitamin D(2) in whole milk, skim milk, or corn oil on toast. After subjects consumed orange juice fortified with 1000 IU vitamin D(3) daily for 12 wk, serum 25(OH)D(3) concentrations increased by 150%, and serum parathyroid hormone concentrations decreased by 25% compared with baseline; control subjects had a seasonal increase of 45% in 25(OH)D and no significant change in serum parathyroid hormone. CONCLUSIONS: The fat content of milk does not affect vitamin D bioavailability. Vitamin D fortification at 1000 IU/240 mL orange juice for 12 wk safely increased 25(OH)D(3) concentrations in adults.     

Surface properties of ceria synthesised using Triton-X based reverse microemulsions

The effect of the tail length of Triton-X surfactants on the surface properties of ceria prepared by means of reversed micelles and Ce(OⁱPr)₄ has been systematically studied. Generally, solids with increased surface areas (up to 136 m² g⁻¹) were synthesised. It was shown that the tail length strongly affects the surface characteristics. Further studies were carried out using UV-Vis, ATR-FTIR, XRD and TGA/DSC studies of the precursor gels as well as N₂-isothermal adsorption BET, XRD, FT-IR, UV-Vis diffuse reflectance and SEM investigations of the final solids samples. An interaction mechanism between the ceria precursor molecules and the polar tail of the reversed Triton X micelles and the formation of ceria (CeO₂) particles in the aqueous nucleus of the reversed microemulsions is proposed.

The effect of the tail length of Triton-X surfactants on the surface properties of ceria prepared by means of reversed micelles and Ce(OⁱPr)₄ has been systematically studied.     

Comparison of long-term results of total fundoplication gastroplasty and Belsey Mark IV antireflux operations in relation to the severity of oesophagitis.

OBJECTIVE: Belsey Mark IV (BM IV) and total fundoplication gastroplasty (TFG) were the standard anti-reflux operations in two consecutive periods in Nottingham City Hospital Thoracic Surgery Unit. The aim of this study was to compare the long-term results obtained by these two procedures emphasizing their relation to the severity of the oesophageal mucosal damage. METHODS: Ninety patients (50 females and 40 males with a mean age of 57 years) who had a BM IV operation between 1976 and 1983 and 86 patients (46 females and 40 males, with a mean age of 56.5 years) undergoing a TFG procedure between 1983 and 1986 were evaluated. All patients were assessed preoperatively by means of clinical history, barium meal and endoscopy. In addition, 72 of the patients having a TFG had prolonged pH monitoring and manometric studies. The unit policy is for life-long follow-up. The symptoms at review were assessed and graded according to the criteria published by Orringer et al. (Orringer MB, Skinner DB, Belsey RHR. Long-term results of the Mark IV operation for hiatal hernia and analyses of recurrences and their treatment. J Thorac Cardiovasc Surg 1972;63:25-33). RESULTS: In the BM IV group there was one post-operative death (1.1%). The median follow-up was 11 years (range 3-18 years). Overall good results were achieved in 64 patients (71.9%). In patients without oesophagitis (n = 24) the success rate was 91.7% while for grades I (n = 17), II-III (n = 36) and IV (n = 12) oesophagitis this was 76.5, 66.7 and 41.7%, respectively (P = 0.01). The actuarial success rate at 10 through to 18 years was 71.0%. In the TFG group there was no postoperative death. The median follow-up was 10 years (range 2-14 years). Overall good results were achieved in 78 patients (90.7%). In the absence of oesophagitis (n = 10) the success rate was 90.0% and for grades I (n = 12), II-III (n = 26) and IV (n = 38) oesophagitis this was 91.6, 92.3 and 89.4%, respectively. The actuarial success rate at 10 through to 14 years was 90.3%. The differences in the overall success rate (P = 0.002), the success rates forgrades II-III (P = 0.02) and IV (P = 0.001) oesophagitis and the long-term actuarial success rates (P = 0.001) were significant. CONCLUSION: These data provide evidence on the superiority of the TFG against the BM IV in achieving long-term relief of reflux symptoms in the presence of severe oesophagitis. We believe that failure of BM IV in this setting is due to obvious or subtle oesophageal shortening.     

Erythromycin as a prokinetic agent in preterm infants.

BACKGROUND: The macrolide antibiotic erythromycin is a prokinetic agent that stimulates gastrointestinal motility. The aim of the study was to determine the effect of erythromycin on the gastrointestinal motility of preterm infants. METHODS: Erythromycin 10 mg/kg, 8 hourly or a placebo, was given orally for 7 days in a double-blind randomized, crossover study of 20 preterm infants with a median gestational age of 32 weeks (range, 26-34 weeks). Antral contractility was determined by using ultrasonography to measure the decrease in the gastric antral cross-sectional area after a feed. The whole gut transit time was assessed by timing the transit of carmine red through the gut. RESULTS: Antral contractility lasted for a shorter period of time during erythromycin treatment than during placebo treatment (mean [standard deviation], 31 minutes [9.9 minutes] vs. 70 minutes [13 minutes]; P < 0.01). Whole gut transit time was also shorter during erythromycin treatment (mean, 23.1 hours [12.9 hours] vs. 49.3 hours [29 hours]; P < 0.01). All infants tolerated the drug well. CONCLUSIONS: Oral erythromycin in food-intolerant preterm infants enhances both antral contractility and whole gut transit time.