Zoledronic acid has been used for prevention of osteolytic and osteoblastic bone metastasis. This case report illustrates an undesirable consequence from prolonged usage of zoledronic acid in bone metastasis prevention. Periprosthetic acetabular fracture in a patient treated with zoledronic acid for 7 years was reported. The clinical presentation, radiographic and pathological results were described. This is a rare complication after total hip arthroplasty which should not be ignored especially in patients who received long term bisphosphonate.
Acetabulum/*injuries/pathology/surgery ; Aged ; Arthroplasty, Replacement, Hip/*adverse effects ; Bone Density Conservation Agents/*adverse effects/pharmacology ; Bone Neoplasms/prevention & control/secondary ; Bone Remodeling/drug effects ; Breast Neoplasms/pathology ; Diphosphonates/*adverse effects/pharmacology ; Female ; Fractures, Spontaneous/chemically induced/etiology ; Hip Prosthesis ; Humans ; Imidazoles/*adverse effects/pharmacology ; Osteoarthritis, Hip/*surgery ; Periprosthetic Fractures/*chemically induced/etiology ; Prosthesis Failure ; Reoperation

OBJECTIVETo explore the effects of p38MAPK inhibitor SB203580 (SB) on the occurrence of acute GVHD and intestine damage after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in mice.

METHODSSixty BALB/c mice, as recipients, were randomized to control group, irradiation group, model group and intervention group. C57BL/6 mice, as donors, were raised to prepare the bone marrow cells (BMCs) and spleen cells (SCs), which were injected into irradiated recipients mice by tail vein. Except control group, other groups accepted 7.5Gy total body irradiation. Model group and intervention group were infused with BMCs 5×10⁶ and SCs 5×10⁵ by less than 4 h after irradiation. SB was injected into intervention group by intraperitoneally, but only DMSO for model group. The general status and survival rate of each group were evaluated. The expression of p-p38MAPK, Fas and FasL in intestine were determined by RT-PCR, Western blot and immunohistochemistry (IHC).

RESULTSThe weight changes of intervention group (13.00±0.50)% was significantly lighter than that of model group (25.00±0.75)% (P<0.05). The clinical score of acute GVHD in the intervention group (3.33±0.82) was significantly lower than that of model group (6.33±1.36) (P<0.05). The expression levels of p-p38MAPK, Fas and FasL in small intestine of intervention group (1.43±0.02, 0.81±0.03, 0.97±0.03) were lower than those of model group (1.76±0.05, 1.52±0.04, 1.48±0.04).

CONCLUSIONSB inhibited the activation of p38MAPK and Fas/ FasL signal pathway and alleviated the apoptosis of small intestine. And SB could relieve small intestine damages induced by allogeneic T lymphocytes.

Animals ; Apoptosis ; drug effects ; Bone Marrow Transplantation ; adverse effects ; Fas Ligand Protein ; metabolism ; Graft vs Host Disease ; metabolism ; pathology ; Imidazoles ; pharmacology ; Intestines ; drug effects ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Pyridines ; pharmacology ; Signal Transduction ; drug effects ; Transplantation, Homologous ; fas Receptor ; metabolism ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism

OBJECTIVETo examine the changes in P38MAPK during and after cardiopulmonary bypass (CPB) and the effect of SB203580, a specific P38MAPK inhibitor, on CPB-induced pulmonary inflammatory response.

METHODSFifty-four SD rats were randomized into 3 groups (each=18), namely sham CPB group, CPB group, and SB203580 group in which rats underwent CPB with SB203580 pretreatment. The lungs were excised immediately after the rats were sacrificed at scheduled time points and p38, nuclear factor-kappaB (NF-kappaB), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were detected.

RESULTSThe activities of P38 MAPK and NF-kappaB were significantly increased in CPB group as compared with those in sham CPB group. CPB resulted in increased TNF-alpha and IL-1beta production in the lung tissues. Administration of SB203580 prevented up-regulation of lung phosphorylated P38 MAPK, and decreased proinflammatory cytokine productions in the lung tissues.

CONCLUSIONP38 MAPK is activated in the lung tissue during and after CPB to affect the activation of NF-kappaB in the lung; SB203580 selectively inhibits P38 MAPK activation to reduce proinflammatory cytokine production after CPB.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Cardiopulmonary Bypass ; adverse effects ; Cytokines ; biosynthesis ; Imidazoles ; pharmacology ; Interleukin-1beta ; biosynthesis ; Lung ; metabolism ; Male ; NF-kappa B ; biosynthesis ; Pyridines ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Systemic Inflammatory Response Syndrome ; metabolism ; Tumor Necrosis Factor-alpha ; biosynthesis ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism