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Background: The oral administration of drug β-d-mannuronic acid (M2000) showed a potent therapeutic effect in phase I/II study in rheumatoid arthritis (RA) patients. Here, our aim is to assess the efficacy and safety of this new drug in RA patients under a multinational, randomized placebo-controlled phase III clinical trial. Method: Patients (n = 288) with active disease at baseline and inadequate response to conventional drugs were randomly allocated to three groups; (1) receiving mannuronic acid at a dose of two capsules (500 mg) per day orally for 12 weeks, (2) placebo-controlled, and (3) conventional. The primary endpoints were the America College of Rheumatology 20 response (ACR20), 28-joint disease activity score (DAS28) and Modified Health Assessment Questionnaire-Disability Index (M-HAQ-DI). In addition, the participants were followed-up for safety assessment. Results: In this phase III trial, after 12 weeks of treatment, there was a significant reduction in ACR20 between mannuronic-treated patients compared to placebo and conventional groups. Moreover, there was a similar significant improvement for DAS28 following mannuronic therapy. The statistical analysis showed a significant reduction in the swollen and tender joint count in mannuronic-treated patients compared with the placebo group. On the other side, mannuronic acid showed no-to-very low adverse events in comparison to placebo. Conclusion: The results of this multinational, phase III clinical trial provided a potent evidence base for the use of β-d-mannuronic acid as a new highly safe and efficient drug in the treatment of RA. [ABSTRACT FROM AUTHOR]

This study was carried out to elucidate the therapeutic efficacy of a new antimalarial drug, artemether, in adriamycin-induced nephropathy. To induce experimental nephrosis, adriamycin was given once by a single intravenous injection through the tail vein. Six days after adriamycin injection, therapeutic protocol was developed by intramuscular (i.m.) administration of 5 mg/kg artemether (ART). The total of i.m. injections were 14, in which five injections were made every day and nine injections were carried out at regular 48-h intervals. The therapeutic protocol was terminated on day 28, and animals were sacrificed on day 49. Our results showed that treatment with ART caused a significant reduction in the level of proteinuria (118 ± 15 vs. 48 ± 21 mg/24 h), urine urea (723 ± 226 vs. 414 ± 185 mg/dL), and urine sodium (38 ± 8 vs. 28 ± 6 mEq/L) compared with nontreated controls. In addition, a decrease in serum cholesterol (250 ± 58 vs. 163 ± 58 mg/dL) and creatinine (1.4 ± 0.2 vs. 0.9 ± 0.2 mg/dL) and an increase in the level of serum albumin (3.3 ± 0.5 vs. 5.6 ± 0.5 g/dL) were significant in the group treated with ART compared with the patient group. Moreover, treatment with ART significantly reduced glomerular PMN and mononuclear cells infiltration, hypercellularity, karyorrhexis, wire loops and hydropic change in the capillary network within the renal cortex, as well as decreased hyalin casts. On the other hand, healthy controls receiving ART showed a significant decrease in amounts of serum triglyceride (174 ± 55 vs. 88 ± 27mg/dL), urine urea (720 ± 113 vs. 511 ± 211 mg/dL), urine sodium (45 ± 5 vs. 26 ± 6 mEq/L), and potassium (71 ± 14 vs. 53 ± 6 mEq/L) compared with the normal group, where significant reduction of urinary excretion of sodium and urea must be considered as a side effect of ART therapy. These data suggest that artemether therapy can ameliorate proteinuria and suppress the progression of glomerular lesions in an experimental model of nephrosis, and that it may be recommended as a lipid-lowering drug. [ABSTRACT FROM AUTHOR]

The present study was designed to test the therapeutic effect of a new antimalarial drug, artesunate in experimental model of nephrotic syndrome. To induce this experimental model, Adriamycin was given once by a single intravenous injection (7.5 mg/kg) through the tail vein. Six days after injection of Adriamycin, therapeutic protocol was developed by intraperitoneally (IP) administration of 5 mg/kg artesunate (ARS). Total of IP injections were 14, of which 5 injections were made every day and 9 injections were carried out at regular 48-h intervals. Therapeutic protocol was terminated on day 28 and animals were killed on day 49. The results showed that treatment with ARS caused a significant reduction in the level of proteinuria, urine urea and urine sodium compared with nontreated controls. In addition, decrease in serum triglyceride and increase in the level of serum albumin was significant in treated group with ARS compared with nontreated controls. Moreover, treatment with ARS significantly reduced glomerular polymorphonuclear (PMN) and mononuclear cells infiltration, hypercellularity, karyorrhexis, wire loops, and hydropic change in capillary network within the renal cortex, as well as decreased hyalin casts. On the other hand, healthy controls receiving ARS showed a significant decrease in amounts of serum triglyceride, urine urea, and urine sodium and potassium compared with normal group. These data suggest that artesunate therapy can ameliorate proteinuria, and suppress the progression of glomerular lesions in experimental model of nephrotic syndrome; it may also be recommended as a lipid-lowering drug. [ABSTRACT FROM PUBLISHER]

The present study was designed to test the therapeutic effect of a new antimalarial drug, artesunate in experimental model of nephrotic syndrome. To induce this experimental model, Adriamycin was given once by a single intravenous injection (7.5 mg/kg) through the tail vein. Six days after injection of Adriamycin, therapeutic protocol was developed by intraperitoneally (IP) administration of 5 mg/kg artesunate (ARS). Total of IP injections were 14, of which 5 injections were made every day and 9 injections were carried out at regular 48-h intervals. Therapeutic protocol was terminated on day 28 and animals were killed on day 49. The results showed that treatment with ARS caused a significant reduction in the level of proteinuria, urine urea and urine sodium compared with nontreated controls. In addition, decrease in serum triglyceride and increase in the level of serum albumin was significant in treated group with ARS compared with nontreated controls. Moreover, treatment with ARS significantly reduced glomerular polymorphonuclear (PMN) and mononuclear cells infiltration, hypercellularity, karyorrhexis, wire loops, and hydropic change in capillary network within the renal cortex, as well as decreased hyalin casts. On the other hand, healthy controls receiving ARS showed a significant decrease in amounts of serum triglyceride, urine urea, and urine sodium and potassium compared with normal group. These data suggest that artesunate therapy can ameliorate proteinuria, and suppress the progression of glomerular lesions in experimental model of nephrotic syndrome; it may also be recommended as a lipid-lowering drug. [ABSTRACT FROM AUTHOR]