Background: Methotrexate has been widely used as an effective systemic therapy for psoriasis. Retrospective data showed efficacy rate of 70-80% but recent RCTs using PASI 75 as primary endpoint showed wide variations in efficacy. Different dosing regimens for methotrexate may explain this variation. Objectives: To compare the efficacy and tolerability of two different dosing regimes of oral methotrexate in patients with moderate to severe plaque psoriasis. Methods: A prospective comparative study was conducted from October 2009 to June 2010. Patients with moderate-to-severe plaque psoriasis were randomized to receive either a ‘step-up dose’ regime (starting dose 7.5mg) or a ‘step-down dose’ regime (starting dose 20mg) of oral methotrexate for 16 weeks. The primary efficacy endpoint was PASI 75. Tolerability and safety were assessed. Results: Forty patients received oral methotrexate with equal numbers in each arm. After 16-week, 55% (11) of patients in ‘step-up dose’ group and 65% (13) of patients in ‘step-down dose’ group achieved PASI 75 (p > 0.05). Significantly higher number of patients in ‘step-down dose’ group achieved PASI 75 at week 4 and week 8 (p < 0.05) compared to ‘step-up dose’ group. One patients from ‘step-down dose’ group discontinued study prematurely due to adverse effect but no significant difference in rate of adverse events was noted. Conclusion: There was no significant difference in efficacy between both regimes at the end of 16 weeks but significant efficacy was observed in patients on ‘step-down dose’ regime as early as week 4. The side effect profile and tolerability were similar.

INTRODUCTION: Our study aimed to identify the factors associated with successful first-time radioactive iodine (RAI) treatment in patients with Graves' disease (GD). MATERIALS AND METHODS: This is a restrospective study of patients with GD who were treated with RAI. Treatment success was defined as onset of permanent hypothyroidism or euthyroidism after 1 dose of RAI at 1-year follow-up. RESULTS: There were 388 GD patients who underwent RAI treatment between January 2014 and December 2015. Of these, 74% achieved treatment success. Median time to achieve permanent hypothyroidism was 2 months. Male gender, smoking, higher antithyroid drug dosage, lower thyroid stimulating hormone (TSH) level, large goitre size and TSH receptor antibody (TRAb) titre at time of RAI were significantly associated with treatment failure. Multivariate analysis showed that larger goitre size and higher TRAb titre were associated with lower first-time RAI success. CONCLUSION Larger goitre size and higher TRAb titre predict lower success of RAI therapy in GD patients. Treatment decisions and strategies should be customised for patients who present with these characteristics.

Background: Inflammation is a crucial process driving pathogenesis in malaria infection. The devastating effects of malaria infection has always been associated with severe inflammation whilst protective effect is linked to provocation of anti-inflammation responses. IL-4, IL-10 and IL-13 are well-established anti-inflammatory cytokines with their functional roles during malaria infection remain elusive. Therefore, this study was undertaken to study the effects of modulating IL-10, IL-4 and IL-13 on the course of malaria infection in Plasmodium berghei ANKA (PbA)-infected murine model. Methods: Male ICR mice were randomly assigned into 5 different groupings and were infected intraperitoneal with 0.2 mL of 2 x 107 pRBCs containing P. berghei ANKA (PbA). Malaria-infected mice were treated with recombinant mouse IL-4 (rmIL-4), recombinant mouse IL-10 (rmIL-10) and recombinant mouse IL-13 (rmIL-13) for 4 consecutive days after the establishment of the infection. The survival and parasitemia levels of malarial mice and malarial mice under different treatments were monitored. Major affected organs (kidneys, lungs, brain, liver and spleen) were subjected to histopathological analysis at day-5 post infection. Results: Our findings revealed that the overall lifespan of malarial mice treated with recombinant mouse rmIL10, rmIL-4 and rmIL-13 were prolonged, accompanied with significant reduction in malaria parasitemia levels, in particular in malarial mice receiving recombinant rmIL-10 and rmIL-13. Histopathological conditions of kidneys, lungs, brain, liver and spleen treated with recombinant mouse rmIL-10, rmIL-4 and rmIL-13 were also improved. Sequestration of parasitized red blood cells (pRBCs) and inflammation seen in major affected organs were alleviated. Conclusion Despite some limitations, this preliminary study demonstrated the promising therapeutic effects of IL-10 and IL-13 as adjuvant therapies in reducing severe pathological manifestations triggered by inflammation during malaria infection.
Malaria

Background: The cytokine cascade in the immunopathogenesis of malaria infection had been widely studied. However, their specific association with survival and severe infection remained obscure.Methods: Thestudy investigated the cytokine profiles and histopathological features of malaria in the severe infection and survival models by using male ICR mice and male Sprague Dawley rats respectively.Results: The severe model, the infected ICR mice, exhibited a high parasitemia with 100% mortality after peak parasitemia at day 5 post-infection. The survival model, the infected Sprague Dawley rats, showed mild parasitemia with full recovery by day 14 of infection. Both severe and survival models showed similar histopathological severity during peak parasitemia. The severe model produced highly elevated levels of pro-inflammatory cytokines, TNF-α and IL-1α, and low levels of the anti-inflammatory cytokine, IL-4; while the survival model showed low levels of TNF-α and IL-1α with high levels of IL-4.Conclusion: There were differences in the pathogenesis of the severe and survival models of malaria infection. These could be a basis for immunotherapy of malaria in the future