Aim: A once-daily formulation of tacrolimus, Advagraf®, is increasingly being used in place of twice-daily
tacrolimus, Prograf®, as a standard immunosuppressive agent for transplant patients. In this study, the
clinical safety and efficacy of Advagraf® were compared with Prograf®, among multi-ethnic Malaysian renal
transplanted population.
Method: This retrospective study identified renal transplant patients who were converted from Prograf® to
Advagraf® at the University Malaya Medical Centre (UMMC) (n=69). Clinical notes and laboratory records,
including tacrolimus daily dose and trough levels, were obtained for one-year, pre-and post-conversion. Causality
assessment of suspected adverse events were based on the WHO-Uppsala Monitoring Center criteria. Renal
biopsy records were re-evaluated based on the updated Banff 2007 classification for biopsy-confirmed acute
rejection (BPAR).
Results: Following conversion to Advagraf®, the mean tacrolimus trough level and daily dose decreased
significantly (p
Respiratory syncytial virus (RSV) is a common pathogen affecting the respiratory tract in infants. To date, there is limited data on RSV occurrence in Malaysia especially in the northeast of Peninsular Malaysia which is significantly affected by the rainy (monsoon) season. This study aimed to determine the prevalence, risk factors (the presence of a male sibling and older school-age siblings, parental education level, monthly income, chronic lung disease, immunocompromised, being a passive smoker, multipara, breastfeeding, prematurity, congenital heart disease, nursery attendance, and rainy season) as well as clinical manifestations of RSV in hospitalized infants and children with lower respiratory tract infection (LRTI). Patients' nasopharyngeal aspirates were tested for RSV antigen, questionnaires, and seasonal variations were used to assess RSV infection. Approximately 22.6% of children were infected with RSV; mean age 7.68 ± 5.45 months. The peak incidence of RSV as a causative agent for LRTI in infants was less than or equal to 1-year old (83%) with approximately 50.5% of the affected children in the younger age group (6 months amd below). RSV infection was significantly but independently associated with the rainy season (odds ratio, 3.307; 95% confidence interval, 1.443-3.688; P
BACKGROUND: The aim of this study was to compare the within-patient variability trough levels (Co), dose-adjusted Co, and dose requirements of Prograf and Advograf with CYP3A5 polymorphisms in Malaysia renal transplant recipients.
METHODS: Stable post-renal transplantation patients switched from Prograf to Advograf were retrospectively identified from University Malaya Medical Centre (n = 28). Co and concomitant tacrolimus dose 6 months preconversion and postconversion were examined. CYP3A5 was genotyped using reverse transcriptase polymerase chain reaction. Wilcoxon signed rank test and Mann-Whitney U test were used to compare Co and dose between formulations and according to genotypes.
RESULTS: There was a significant difference in the whole-blood tacrolimus Co between the 2 groups (6.16 ± 1.74 ng/mL vs 4.90 ± 1.06 ng/mL; P = .0001). The mean daily maintenance dose of Prograf was 3.9 ± 2.0 mg/kg (0.06 mg/kg/d), which was reduced to 3.3 ± 1.7 mg/d (0.04 mg/kg/d) with Advograf (P = .01). The mean maintenance dose of tacrolimus required for those with CYP3A5*1/*1 (high-expressive) was significantly higher than those with CYP3A5*1/*3 (intermediate-expressive) and CYP3A5*3/*3 (low-expressive) (P < .01) for both formulations. Comparing those with CYP3A5*1/*1, the average dose-adjusted Co was significantly higher in patients with CYP3A5*3/*3 with Advograf (P < .05).
CONCLUSIONS: The requirement for daily maintenance dose was higher in those with CYP3A5*1/*1 variants in both tacrolimus formulations in the Malaysian patients. Furthermore, those with CYP3A5*3/*3 demonstrated significantly higher dose-adjusted Co with Advograf.
Activated pancreatic stellate cells (PSCs) have been widely accepted as a key precursor of excessive pancreatic fibrosis, which is a crucial hallmark of chronic pancreatitis (CP) and its formidable associated disease, pancreatic cancer (PC). Hence, anti-fibrotic therapy has been identified as a novel therapeutic strategy for treating CP and PC by targeting PSCs. Most of the anti-fibrotic agents have been limited to phase I/II clinical trials involving vitamin analogs, which are abundant in medicinal plants and have proved to be promising for clinical application. The use of phytomedicines, as new anti-fibrotic agents, has been applied to a variety of complementary and alternative approaches. The aim of this review was to present a focused update on the selective new potential anti-fibrotic agents, including curcumin, resveratrol, rhein, emodin, green tea catechin derivatives, metformin, eruberin A, and ellagic acid, in combating PSC in CP and PC models. It aimed to describe the mechanism(s) of the phytochemicals used, either alone or in combination, and the associated molecular targets. Most of them were tested in PC models with similar mechanism of actions, and curcumin was tested intensively. Future research may explore the issues of bioavailability, drug design, and nano-formulation, in order to achieve successful clinical outcomes with promising activity and tolerability.