OBJECTIVE: To evaluate the effectiveness of IL-10 in suppressing 18F-FDG uptake in the inflammatory granuloma of SD rats. METHODS: Eight SD rats were killed, and their blood was collected sterily. After centrifugion, the white blood cells were incubated in PRMI 1640 for 3 days. Then each culture flask of white blood cells was divided into two equal parts. To one group was added 0.2 mL IL-10 solution (0.1 mg/mL); to the control was added with 0.2 mL of 0.9% sodium chloride solution. All cells were then incubated for 120 minutes at 37 degree, after which 18F-FDG (1.85 MBq) was added. Sixty minutes later, the cells were washed twice with PBS and the extent of uptake 18F-FDG determined. In vivo, an inflammatory granuloma was produced by hypodermic injection of rats with a mixture of Freund's complete adjuvant, bovine serum albumin and talcum powder. Each rat was maintained for 8 weeks. Imaging of the inflammatory granulomas was performed using the 18F-FDG signal. IL-10 was injected into SD rats at 10 μg/kg of body weight. Sixty minutes later, 7.4 MBq of 18F-FDG were injected, and, after a further 60 minutes, the rats underwent a PET-CT scan. The region of interest (ROI) of the inflammatory granuloma was delineated and the standard uptake value (SUV) calculated. A second PET-CT scan was done without IL-10 on the next day. The granulomatous tissue underwent pathological examination. RESULTS: In the intro test, the with blood cell uptaking ratio of 18F-FDG was (50.3±6.7)% without IL-10, and (34.6±3.5)% with IL-10(t=8.9, P<0.01). IL-10 suppressed the rat white blood cell uptaking 18F-FDG. In the PET-CT scan, the SUV of ROI on inflammatory granuloma was 1.7±0.4 with IL-10 and 2.1±0.3 without IL-10 (t=20.6, P<0.01). IL-10 suppressed the inflammatory granuloma uptaking 18F-FDG. CONCLUSION IL-10 can suppress the inflammatory granuloma of SD rats uptaking 18F-FDG.
Animals ; Female ; Fluorodeoxyglucose F18 ; pharmacokinetics ; Freund's Adjuvant ; Granuloma ; chemically induced ; metabolism ; Interleukin-10 ; pharmacology ; Lung Diseases ; chemically induced ; metabolism ; Male ; Radiopharmaceuticals ; pharmacokinetics ; Rats ; Serum Albumin, Bovine

We investigated whether amyloid beta (Abeta) aggregates have transforming growth factor beta- like cytokine activity and cause transdifferention of lens epithelial cells, leading to certain types of cataract. In order to mimic Abetaaggregates, Abeta- (1-40) was crosslinked to bovine serum albumin (BSA) with disuccinimidyl suberate according to a previously described procedure. When human lens epithelial B-3 (HLE B-3) cells were treated with the Abeta- (1-40) -BSA conjugates, we observed the translocation of Smad-3, as well as the induced mRNA levels of fibronectin (FN), collagen type I (Col I), smooth muscle actin (SMA) and matrix metalloproteinase-2 (MMP-2). In addition, we investigated the morphology of rat whole lens cultured for 5 days in the presence of Abeta- (1-40) -BSA, and the immunohistochemical localizations of Abeta- (1-40) /amyloid precursor protein (APP) in human clinical tissues beneath the anterior capsules. In rat whole lens cultures, treatment with Abeta- (1-40) -BSA produced a transformed morphology that had multiple layers of lens epithelial cells. To compare the anterior capsules in anterior subcapsular cataracts with those in nuclear cataracts, immunohistochemical studies of Abeta/APP in human clinical tissues revealed that the predominant immunostaining of Abeta occurs in the anterior epithelial plaques, which likely produces the abnormal extracellular matrix. Thus, these findings suggest that Abeta aggregates in vivo are possibly involved in the regulatory process by which lens epithelial cells may transdifferentiate into fibroblast-like cells, as well as help understand the mechanisms which lead to certain types of cataractogenesis.
Amyloid beta-Protein/*pharmacokinetics ; Animals ; Cataract/*metabolism/pathology ; Cell Differentiation ; Cell Line ; Epithelial Cells/*cytology/*metabolism ; Human ; Lens, Crystalline/*cytology ; Peptide Fragments/*pharmacokinetics ; Rats ; Serum Albumin, Bovine/*pharmacokinetics ; Support, Non-U.S. Gov't

It is generally believed that liposomes modified with polyethylene glycol (PEG) have no or lower immunogenicity. However, based on many recent literatures, when the PEGylated liposomes were repeatedly applied to the same animal, the immune responses occurred. The first injection of PEGylated liposomes resulted in a reduction in the circulation time and an increase in hepatic and splenic accumulation of the second dose of PEGylated liposomes in a time-interval, which was called "accelerated blood clearance (ABC)" phenomenon. Such immunogenicity of PEGylated liposomes presents a barrier in the research of liposomal formulations and their use in the clinics. This review focused on the definition, the method of verification, the development of the reason for ABC phenomenon, influencing factors of ABC phenomenon, and discussed if other PEGylated nanocarriers also induce ABC phenomenon.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Doxorubicin ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Immunoglobulin M ; biosynthesis ; blood ; Liposomes ; administration & dosage ; blood ; pharmacokinetics ; Liver ; metabolism ; Metabolic Clearance Rate ; Particle Size ; Polyethylene Glycols ; administration & dosage ; metabolism ; pharmacokinetics ; Serum Albumin, Bovine ; pharmacokinetics ; Spleen ; immunology ; metabolism

To study the preparation, activity and targeting ability evaluation in vitro on epigallocatechin-3-gallate (EGCG) bovine serum albumin nanoparticles targeting to PC-3 cells, the folate mediated EGCG bovine serum albumin nanoparticles (FA-EGCG-BSANP) were prepared by desolvation process. The morphology and particle size of the nanoparticles were determined by atomic force microscope (AFM). HPLC was used to analyse the entrapment efficiency and drug loading rate of EGCG The amount of folate conjugation on the BSANP was determined by quantitative ultraviolet (UV) spectrophotometer analysis. The targeting ability to PC-3 was observed using laser scanning confocal microscope (LSCM) and fluorophotometer microscope. And the activity of FA-EGCG-BSANP was mensurated by MTT method. The morphology and particle size distribution of FA-EGCG-BSANP were uniform and even with the mean particle size of 200 nm. The entrapment efficiency and loading rate of EGCG were (81.5 +/- 1.8) % and (29.3 +/- 0.6) %, respectively, and the amount of folate conjugation was 18.363 microg x mg(-1) BSA. The FA-EGCG-BSANP uptakes by cultured PC-3 cells were 23.65 times the amount of EGCG-BSANP in a concentration dependant manner. The lethality of PC-3 cells treated with FA-EGCG-BSA was 82.8%, while those treated with EGCG and EGCG-BSANP were 58.6% and 55.1%, respectively. And lethality of PC-3 cells was positively correlated with the nanoparticles uptake amount. FA-EGCG-BSANP can significantly promote EGCG to PC-3 cells sites and improve their efficacy, which is considered to an experimental foundation for further research on its activity, targeting ability and metabolism in vivo.
Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; pharmacology ; Catechin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; pharmacology ; Cell Death ; drug effects ; Cell Line, Tumor ; Drug Carriers ; Drug Compounding ; Drug Delivery Systems ; methods ; Folic Acid ; administration & dosage ; chemistry ; pharmacokinetics ; Humans ; Male ; Nanoparticles ; Particle Size ; Prostatic Neoplasms ; metabolism ; pathology ; Serum Albumin, Bovine ; chemistry ; pharmacokinetics ; pharmacology