Quantitative assessment of steroid amount in the tissue after epidural steroid injection: a new rabbit model

BACKGROUND: To develop a rabbit epidural steroid injection (ESI) model for analyzing steroid retention in the tissue, and to assess the difference in steroid retention in the model according to the location and time elapsed after ESI. METHODS: Fluoroscopy-guided ESI was performed using the interlaminar approach between the lowest two lumbar segments in 13 female New Zealand white rabbits. Four rabbits were allocated to each of three different groups according to the time of sacrifice: 3, 7, and 15 days post-ESI; the remaining rabbit was sacrificed immediately post-ESI to obtain baseline data. After sacrifice, two segments were harvested: the lowest two lumbar vertebrae and another two lumbar vertebrae immediately above these. The residual steroid amount (RSA) and residual steroid concentration (RSC) in the collected spinal columns were analyzed. A linear mixed model was used to compare RSAs and RSCs between the injected and adjacent segments, and among the number of days until sacrifice; P < 0.05 was considered statistically significant. RESULTS: Both RSA and RSC of the injected segment were significantly higher than those of the adjacent segment (P < 0.001, both). The RSA and RSC significantly decreased over time (P = 0.009 and P = 0.016, respectively). CONCLUSIONS: The developed rabbit ESI model verified that significantly more steroid was retained at the injected segment than at the adjacent segment and the residual steroid decreased over time. This model could be useful not only for comparing current steroid medications, but also for developing new, better steroid formulations.

Effect of Poly(Lactide-Co-Glycolide) Nanoparticles on Local Retention of Fluorescent Material: An Experimental Study in Mice

OBJECTIVE: Poly(lactide-co-glycolide) (PLGA) nanoparticles are promising materials for the development of new drug-releasing systems. The purpose of this study was to evaluate the in vivo retention time of materials loaded in nanoparticles as compared with that of the material alone by in vivo imaging in nude mice. MATERIALS AND METHODS: Mice (n = 20) were injected with 0.1 mL fluorescent material 1,1′-dioctadecyl-3,3,3′,3′ tetramethylindotricarbocyanine iodide (DiR)-loaded PLGA nanoparticles (200 nm) into the right paraspinal muscle, and the same volume of pure DiR solution was injected into the left paraspinal muscle. Fluorescence images were obtained using an in vivo optical imaging system. Fluorescent images were taken 1 day after the injection, and seven more images were taken at 1-week intervals. Image analysis was done with ImageJ program, and one region of interest was chosen manually, which corresponded to the highest signal-intensity area of fluorescence signal intensity. RESULTS: After 7 weeks, 12 mice showed a right-sided dominant signal, representing the DiR loaded PLGA nanoparticles; 5 mice showed a left-side dominant signal, representing the free DiR solution; and 3 mice showed no signal at all beginning 1 day after the injection. During the 7-week period, the mean signal intensities of the free DiR solution and DiR-loaded PLGA nanoparticles diverged gradually. On day 1, the mean signal intensity of free DiR solution was significantly higher than that of DiR-loaded PLGA (p < 0.001). Finally, by week 7, DiR-loaded PLGA express significantly high signal intensity compared with free DiR solution (p = 0.031). CONCLUSION: The results of the current study suggested that therapeutic agents bound to PLGA nanoparticles may exhibit prolonged retention times.

Comparison of Piroxicam Pharmacokinetics and Anti-Inflammatory Effect in Rats after Intra-Articular and Intramuscular Administration

This study evaluated the pharmacokinetic profile and therapeutic efficacy of piroxicam (PX), a long acting non-steroidal anti-inflammatory drug for the treatment of arthritis, following intra-articular (IA) injection in comparison to the pharmacokinetic profile and therapeutic efficacy of PX after intramuscular (IM) injection. In the pharmacokinetic study in rats, systemic exposure and pharmacokinetic parameters of PX after a single IA dose were compared with systemic exposure and pharmacokinetic parameters of PX after administration of the same dose IM (0.6 mg/kg). The anti-inflammatory and analgesic effects of IA PX were evaluated simultaneously in a monoiodoacetate-induced osteoarthritis rat model. The plasma PX concentration rapidly rose following IA injection, and it was comparable to the plasma PX concentration following IM injection, suggesting the rapid efflux of the drug molecule from the joint cavity. However, in the efficacy study, the IA PX administration significantly reduced the knee swelling by reducing the level of prostaglandin E2 in the joint, compared to that following administration of IA vehicle and after administration of the IM PX dose. In addition, we found that the anti-inflammatory and anti-nociceptive efficacies of IA PX were synergistically increased upon co-treatment with hyaluronic acid (HA), a potent agent for the treatment of osteoarthritis, at the weight ratio of 1:1 or 1:2, and these effects were more pronounced than those following administration of HA or PX alone. In conclusion, this study demonstrated the efficacy of the IA use of PX alone and/or in combination with HA in osteoarthritis.

Factors to Predict Autologous CD34 Positive Cells Harvest in the Patients with Malignant Lymphoproliferative Disorder

BACKGROUND: Autologous peripheral blood stem cell transplantation (PBSCT) has been used as a major treatment strateg for malignant lymphoproliferative disorder. The number of CD34 positive cells in the harvested product is a very important factor for achieving successful transplantation. We studied the factors that can predict the number of CD34 positive cells in the harvested product of multiple myeloma (MM) and Non-Hodgkin's lymphoma (NHL) patients after mobilizing them with chemotherapy plus G-CSF. METHODS: A total of 69 patients (MM 25 patients, NHL 44 patients) with malignant lymphoproliferative disorder had been mobilizedwith chemotherapy and granulocyte colony-stimulating growth factor from January, 2003 to July, 2008. We analyzed the clinical characteristics, the peripheral blood (PB) parameters and the number of CD34 positve cells in the PB and their correlation with the yield of PBPCs collected from the mobilized patients. RESULTS: The total number of leukapheresis sessions was 134 (mean: 1.94 session per patient), and the mean number of harvested CD34 positive cell per patient was 12.47x10(6)/kg. The number of harvested CD34 positive cells was correlated with the patient's height, the number of peripheral blood hematopoietic progenitor cells (HPC) and the number of PB CD34 positive cells at the harvest (P or =23.7/microliter) at the harvest might be the predictor of harvesting more than 3x10(6)/kg CD34 positive cell for autologous PBSCT in patients with malignant lymphoproliferative disorder.

Hodgkin's Lymphoma-like Posttransplantation Lymphoproliferative Disorder after Allogeneic Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) recipients have a risk of post-transplant lymphoproliferative disorder (PTLD), which normally develops in Epstein-Barr virus (EBV) transformed donor B lymphocytes. The incidence of Hodgkin's lymphoma (HL) ranges from 1.8% to 3.4% of PTLD after HSCT. There are no case reports of early onset HL-like PTLD that developed less than one year after HSCT. We encountered a case of early onset PTLD after an unrelated HSCT following reduced-intensity conditioning with cyclophosphamide/fludarabine/thymoglobulin. A 24 year old patient with severe aplastic anemia developed multiple lymphadenopathies at day 95 after HSCT. The excisional biopsy revealed HL-like PTLD, which tested positive to immunohistochemical staining for the EBV. The Ann Arbor stage was IIA. Immunosuppressive agents were discontinued for 2 weeks in order to induce a graft-versus-lymphoma effect without a response. A total 4 cycles of chemotherapy with doxorubicin (adriamycin)/bleomycin/ vinblastine/dacarbazine (ABVD) and radiotherapy (total dosage 3,400 cGy) were then carried out. The response to salvage treatment was complete remission. The patient showed no evidence of the disease at the follow-up performed 32 months after HSCT.