High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis.

Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

Anti-endothelial cell antibodies in connective tissue diseases associated with pulmonary arterial hypertension.

OBJECTIVE: To investigate the prevalence of anti-endothelial cell antibodies (AECA) in connective tissue diseases (CTD) associated with pulmonary arterial hypertension (PAH) and to corroborate the pathologic function of AECA in PAH-associated CTDs. METHODS: AECA were detected by cellular enzyme-linked immunosorbent assay (ELISA) in sera of 19 PAH-associated CTD patients, 22 CTD patients without PAH involvement, and 20 age- and sex-matched healthy individuals as controls. Using IgG purified from the sera of AECA-positive, AECA-negative, and healthy subjects, the effects of AECA on the expression of ICAM-1 and the chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) in cultured endothelial cells were also evaluated. RESULTS: A total of 12 of the 19 (63.2%) CTD patients with PAH, 9 of the 22 (40.9%) CTD patients without PAH, and 1 of the 20 (5%) healthy controls were positive for AECA, which were calculated as ELISA ratio (ER) values. ER values in PAH-associated CTD patients were significantly higher than those with CTD without PAH (3.68±2.05 versus 1.67±1.07, P<0.001). IgG purified from AECA-positive sera induced a significantly increased level of ICAM-1 expression after 48 h incubation (795.2±32.5 pg/mL) compared with AECA-negative or healthy control IgG (231.5±27.1 and 192.8±33.4 pg/mL, respectively; P<0.001). In addition, RANTES production by cultured human pulmonary arterial endothelial cells (HPAECs) increased in both a time- and concentration-dependent manner in response to incubation with purified AECA-positive IgG. CONCLUSIONS: AECA could be involved in CTD and might participate in the pathogenesis of PAH-associated CTD.

Suppression of liver regeneration affects hepatic graft survival in small-for-size liver transplantation in rats.

AIM: Small-for-size liver transplantation (SFSLT) often results in hepatic graft failure and decreased survival. The present study was aimed to investigate the possible mechanism of hepatic graft failure in SFSLT in rats. METHODS: Rat models of full-size orthotopic liver transplantation, 50% partial liver transplantation and 30% partial liver transplantation were established. Proliferative responses of the hepatic graft were evaluated by immunohistochemical staining and western blotting. Apoptosis-, inflammatory-, anti-inflammatory- and growth factor-related genes were screened by quantitative reverse transcription polymerase chain reaction. Activities of transcription factors of AP-1 and nuclear factor (NF)-κB were analyzed by electrophoretic mobility shift assay. RESULTS: A 30% partial liver transplant not only resulted in marked structural damages to the hepatic graft, but also showed the lowest 7-day survival rate. In addition, sup pressed expressions of proliferating cell nuclear antigen (PCNA) and cyclin D1 by immunohistochemical staining and decreased expressions of cyclin D1 and p-c-Jun by western blotting were detected. Downregulated expressions of Bcl-2, Bcl-XL, interleukin (IL)-6, IL-10, IP-10 and CXCR2, upregulated expression of tumor necrosis factor-α, and decreased levels of AP-1 and NF-κB were also found following 30% partial liver transplantation after reperfusion. CONCLUSION: Liver regeneration is remarkably suppressed in SFSLT. The significant changes of intra-graft gene expression described above indicated that ischemia reperfusion injury would be severe in 30% partial liver transplantation. The capability of liver regeneration secondary to ischemia reperfusion injury might determine hepatic graft survival in SFSLT.