The production of reactive oxygen species in tacrolimus-treated glial cells.

OBJECTIVE: After organ transplantation, some patients suffer from mild neurological symptoms, such as tremor, to severe complications, including seizures and encephalopathy. These neurological side effects can be caused by immunosuppressants such as tacrolimus. However, the mechanism of encephalopathy by tacrolimus is not fully understood. METHODS: We measured the production of reactive oxygen species (ROS) in glioma cells after tacrolimus treatment. Tacrolimus added to glioma cells was incubated for 60 minutes at 37 degrees C. The production of ROS was evaluated by measuring the fluorescent product from the oxidation of an oxidant-sensitive 2',7'-dichlorofluorescin using VICTOR3TM multilabel counter. RESULTS: Tacrolimus resulted in the production of the ROS in glioma cells. The production of the ROS was increased in time-dependent fashion. CONCLUSIONS: These findings indicated that the tacrolimus may contribute the neurological side effects by ROS production.

Cytokine array after cyclosporine treatment in rats.

OBJECTIVES: Long-term treatment with cyclosporine (CsA) results in chronic nephrotoxicity, which is known to be mediated by several cytokines including transforming growth factor-betal. Cytokines are known to play an important role in innate immunity, apoptosis, angiogenesis, cell growth, and differentiation. They are known to be involved in most disease processes, including cancer, cardiac disease, and nephrotoxicity. To evaluate changes of cytokines in a rat model of CsA-induced chronic nephrotoxicity, we performed a cytokine array. METHODS: Experiments were performed on two groups of rats; normal control group and CsA-treated group. Cytokine array in rat serum was performed using Cytokine Antibody Array I kit from RayBiotech. RESULTS: Serum creatinine, urine creatinine, and creatinine clearance increased in the CsA-treated group. Among the several cytokines, the expressions of the lipopolysaccharide-induced CXC chemokine (LIX), monocyte chemoattractant protein 1 (MCP-1), nerve growth factor (beta-NGF), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the CsA-treated group were increased above that of cytokines in the control group. The density of the LIX in controls was 0.62, and in the CsA-treated group was 1.24. The density of the MCP-1 in controls was 0.68, and in CsA-treated, 1.43. The density of the beta-NGF in controls was 0.62, and that in CsA-treated, 1.24. The density of the TIMP-1 in controls 1.13, and in CsA-treated, 1.40. CONCLUSIONS: Our data suggested that among several cytokines elevated levels of the LIX, MCP-1, beta-NGF, and TIMP-1 are the contributing factors to CsA-induced nephropathy.

Effects of tacrolimus on antioxidant status and oxidative stress in glioma cells.

OBJECTIVES: After organ transplantation, some patients suffer from mild neurologic symptoms, ranging from tremor to severe complications, including seizures and encephalopathy. Among the immunosuppressants, tacrolimus can cause neurologic side effects. However, the mechanisms of encephalopathy by tacrolimus are not fully understood. We measured the antioxidant status, hydrogen peroxide level, and malondialdehyde level in glioma cells after tacrolimus treatment. METHODS: The production of hydrogen peroxide was determined by the modified xylenol orange method. The amount of malondialdehyde was measured by the thiobarbituric acid assay, which is based on malondialdehyde reaction with thiobarbituric acid to give a red species absorbing at 535 nm. Total antioxidant status (TAS) was measured using TAS kits (NX2332). RESULTS: Tacrolimus resulted in dose- and time-dependent increases in the production of hydrogen peroxide by glioma cells. The antioxidant status decreased in the glioma cells after tacrolimus treatment. Malondialdehyde level was unchanged in the glioma cells after tacrolimus treatment. CONCLUSIONS: Increased production of reactive oxygen species and decreased antioxidant status by tacrolimus in glioma cells may contribute to neurologic side effects.

Effects of cyclosporine on the production of the reactive oxygen species in the glial cells.

OBJECTIVES: After organ transplantation, some patients suffer mild neurological symptoms such as tremor to severe complications including seizures and encephalopathy. Among the immunosuppressants, cyclosporine (CsA) can induce neurological side effects. However, the mechanisms of encephalopathy by CsA are not fully understood. We measured the production of reactive oxygen species (ROS) in the glioma cells after CsA treatment. METHODS: CsA (2.5 mmol/L) added to glioma cells was incubated for 60 minutes at 37 degrees C. ROS production was evaluated by measuring the fluorescent product from the oxidation of an oxidant-sensitive 2',7'-dichlorofluorescin using VICTOR3 multilabel counter. RESULTS: CsA resulted in ROS production by glioma cells. The ROS production increased with the time of exposure to CsA. CONCLUSIONS: These findings indicated that CsA may contribute to neurological side effects via ROS production.

Acute colitis associated with dengue fever in a renal transplant recipient.

Dengue fever is a significant health problem for international travelers to all endemic area. Dengue fever is characterized by a sudden onset of fever, headache, rash, myalgia, and joint pain. Infection with the dengue virus is detrimental to a immunosuppressed renal transplant patients. Herein we report a 29-year-old woman living-related renal transplant recipient returning from Southeast Asia with dengue fever presenting as acute colitis. The patient traveled to Southeast Asia for 1 week. She developed watery diarrhea in the second week after the onset of symptoms of dengue fever. Laboratory findings were leukopenia, thrombocytopenia, and elevated serum transaminase levels. Sigmoidoscopic features showed nonspecific acute colitis. She improved after 10 days of hospitalization with intensive supportive care and continuous tacrolimus monotherapy. Altered clinical symptoms are manifested in immunologically naïve adults. Manifestation of unusual symptoms does not exclude dengue virus infection in renal transplant recipients.

Rectal carcinoid tumor in a renal transplant patient.

Malignancy represents a leading cause of morbidity and mortality in patients with a long-term surviving graft. Carcinoid tumor is a common primary endocrine tumor in the general population that is rare in transplant recipients. Our present report focused on a 48-year-old man who received immunosuppressive therapy based on cyclosporine and steroids. Twelve years after renal transplantation, he suffered watery diarrhea and abdominal discomfort. Colonoscopy showed a hard, sessile mass at 5 cm from the anal verge; endoscopic ultrasound showed a 13-mm homogenous hypoechoic mass. Upon endoscopic biopsy, the histological examination revealed a carcinoid tumor. Immunosuppresion was reduced and we performed endoscopic mucosal resection of the rectum. His clinical course has been good with no demonstrated recurrence.

Case of adult mumps infection after renal transplantation.

Viruses are the most common cause of opportunistic infections, important complications of transplantation. Mumps infection in renal transplant recipients is uncommon. This report focused on a 23-year-old woman who received immunosuppressive therapy based on tacrolimus, prednisolone, and mycophenolate mofetil for renal transplantation. Sixteen months after transplantation, she was admitted with pain and swelling in both infra-auricular areas. Laboratory findings demonstrated positive mumps IgM and IgG antibodies and an increased serum amylase level. Computed tomography revealed both parotid glands to be diffusely enlarged. After the diagnosis of mumps parotitis, the patient's immunosuppression was reduced and the clinical course was satisfactory.

Delayed presentation of arteriovenous fistula and pseudoaneurysms in a renal transplant patient 10 years after percutaneous allograft biopsy.

A 51-year-old man was admitted with microscopic hematuria at 10 years after living donor renal transplantation. In order to distinguish between acute tubular necrosis and acute rejection, a graft biopsy was performed under ultrasound guidance at 1 month posttransplantation. Doppler sonography revealed 3 pulsatile cystic masses and an arteriovenous fistula (AVF) in the lower kidney pole. Selective transplant renal angiography revealed 3 pseudoaneurysms with an AVF supplied by a lobular artery in the lower pole. The diagnosis was AVF with pseudoaneurysm, which developed secondary to percutaneous renal allograft biopsy. Interventional treatment was performed because of the high risk for pseudoaneurysm rupture. The AVF and pseudoaneurysms were treated successfully by percutaneous transluminal embolization; renal function remained stable after embolization.