Lemnalol attenuates mast cell activation and osteoclast activity in a gouty arthritis model.

OBJECTIVES: In this study, we investigated the effects of a soft coral-derived anti-inflammatory compound, lemnalol, on mast cell (MC) function and osteoclast activity in rats with monosodium urate (MSU) crystal-induced gouty arthritis. METHODS: In this study, we examined the therapeutic effects of lemnalol on intra-articular injection of MSU induces gouty arthritis with the measurement of ankle oedema. Toluidine blue staining were used to analyse the infiltration and the percentage degranulation MCs. Immunohistochemical analysis showed CD117, transforming growth factor beta 1 (TGF-ß1), matrix metalloproteinase 9 (MMP-9), the osteoclast markers cathepsin K and tartrate-resistant acid phosphatase (TRAP) protein expression in ankle tissue. KEY FINDINGS: We found that both infiltration and degranulation of MCs increased at 24 h after MSU injection in the ankle joint. Immunohistochemical analysis showed that MSU induced upregulation of TGF-ß1, MMP-9, the osteoclast markers cathepsin K and TRAP in ankle tissues. Administration of lemnalol ameliorated MSU-induced TGF-ß1, MMP-9, cathepsin K and TRAP protein expression. CONCLUSIONS: Taken together, our results show that MSU-induced gouty arthritis is accompanied by osteoclast-related protein upregulation and that lemnalol treatment may be beneficial for the attenuation of MC infiltration and degranulation and for suppressing osteoclast activation in gouty arthritis.

Effect of deferiprone on liver iron overload and fibrosis in hepatitis-C-virus-infected thalassemia.

To assess the effects of liver iron overload and fibrosis after treatment with a chelating agent in hepatitis C virus (HCV)-infected thalassemia, from April 1999 to July 2004, 45 patients with thalassemia major (age range 9-33 years, mean 19.3) received daily deferiprone (L1) for 23-60 months (75 mg/kg). The patients were divided into two groups on the basis of their hepatitis status (27 with, 18 without). Their serum was analyzed for alanine aminotransferase (GPT), aspartate aminotransferase (GOT), bilirubin (total/direct), r-glutamyl transpeptidase (r-GT), alkaline phosphatase (Alk-P), and ferritin. Liver iron overload and fibrosis were defined by a senior pathologist. No significant differences were demonstrated in serum levels of GPT, GOT, bilirubin, r-GT, Alk-P or ferritin; comparison was made for each group before and after L1 treatment. Iron scores were 2.3 +/- 0.9 and 2.8 +/- 0.9 for the hepatitis C negative and positive groups, respectively (p = 0.07), with liver fibrosis scores of 1.0 +/- 0.5 and 0.4 +/- 0.52 (p = 0.56). The two scores were not higher for the positive group. There was no evidence of: 1) greater iron overload and fibrosis in the HCV-infected thalassemic patients; 2) L1 inducing progressive hepatic fibrosis or worsening iron overload in HCV-infected thalassemic patients after long-term therapy; 3) further damage to liver cells associated with L1 treatment.

Liver fibrosis and iron levels during long-term deferiprone treatment of thalassemia major patients.

Deferiprone (L1) is an orally active iron-chelation agent that is being evaluated as a treatment for iron overload in thalassemia major. Although some reports have concluded that LI may exacerbate hepatic fibrosis and the deterioration of liver function in thalassemia patients, other studies have reported no detrimental effects. In view of these serious concerns regarding the hepatic toxicity of LI, a Taiwanese group of beta-thalassemia (thal) patients with the longest known duration of LI therapy and who had provided liver biopsies, were enrolled in this study. From April 1999 to July 2004, the 17 enrolled thalassemia major patients had been on L1 therapy for as long as 19 to 60 months. Two liver biopsies from each of the 17 patients were received at the China Medical University Hospital, Taichung, Taiwan. Serum alanine aminotransferase (ALT), viral serological studies for hepatitis B and hepatitis C, iron scores and fibrosis scores were available at the beginning of the study and at the time of the second biopsy. Overall, the 17 patients received L1 therapy continuously for a mean period of 3.3 years. With the exception of two patients, fibrosis scores decreased in all patients after LI therapy. Three patients had increased iron scores after therapy of L1 and 11 patients had increased ALT levels; increased ALT levels occurred more frequently in hepatitis C positive patients. In this study, most thalassemia major patients had no progression of hepatic fibrosis or increased liver iron stores during long-term LI therapy.

Glutathione S-transferase M1 gene polymorphisms are associated with cardiac iron deposition in patients with beta-thalassemia major.

Patients with beta-thalassemia (thal) major are subject to peroxidative tissue injury by iron overload. Glutathione S-transferases work as antioxidants, and their activity is determined genetically. In this study, we used multiplex polymerase chain reaction (m-PCR) to analyze polymorphisms of two endogenous antioxidant agents, glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1), and to determine their roles in 41 patients with beta-thal major. Our results showed that the GSTM1 and GSTT1 null genotypes were not associated with any incidence of endocrine dysfunction (including diabetes mellitus, hypogonadism, hypothyroidism, and growth hormone deficiency), liver function, or impaired left ventricular ejection fraction (LVEF). The GSTM1 null genotype, but not the GSTT1 null genotype, was associated with a decreased signal intensity ratio on cardiac magnetic resonance imaging (MRI). Our results suggest that genetic variations of the GSTM1 enzyme are associated with cardiac iron deposition in patients with beta-thal major.

Deferiprone or deferoxamine vs. combination therapy in patients with beta-thalassemia major: a case study in Taiwan.

Deferiprone (L1) has been recommended as an effective oral chelation therapy for patients with beta-thalassemia major (TM). From 1999 to 2004, 114 patients with TM from five treatment centers were enrolled in this program: iron (Fe) was chelated with L1 in 57 patients, deferoxamine (DFO) in 26, and combined L1/DFO therapy in 31. We found that serum ferritin (SF) was significantly lower in nine patients receiving L1 for more than 5 years (p = 0.04), 22 patients receiving L1 for 1-2 years (p < 0.01) and 31 receiving the combined therapy (p = 0.01), yet significantly higher in those receiving DFO only (p < 0.01). One patient showed transient neutropenia; arthropathy in one patient and gastrointestinal upset in two were noted, with no significant change in alanine aminotransferase (ALT) level. Of 17 patients who were submitted to a liver biopsy, 15 showed no significant change in hepatic fibrosis scores after therapy with L1. None of the 88 patients, including 31 who received the combined therapy, have abandoned oral L1 treatment due to adverse effects. Results of this study proved that L1 or combined therapy with L1 and DFO is effective in reducing SP; incidence of adverse events was low in patients with TM.