Lamotrigine (LTG) is a commonly used antiepileptic drug. However, the use of LTG is limited because of its cutaneous adverse drug reactions (cADRs) ranging from mild maculopapular eruption (MPE) to severe Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A strong association between HLA-B*1502 and carbamazepine-induced SJS ⁄ TEN has been identified in Chinese and Thai. Although three of seven cases with HLA-B*1502 have been reported in LTG-induced SJS ⁄ TEN so far, the relationship between HLA-B*1502 and LTG-induced SJS ⁄ TEN needs further investigation. It is also unclear whether there is a specific genetic marker associated with LTG-induced MPE in Chinese. In this study, we genotyped 43 Han Chinese patients treated with LTG (14 cases with LTG-induced cADRs and 29 LTG-tolerant controls), using PCR-SSP for HLA-B*1502 testing and low-resolution genotyping, as well as sequencing for four-digit genotyping. The two cases with SJS were negative for HLA-B*1502, with B1301 ⁄ 1301 and 4601 ⁄ 5610, respectively. Combining the data with previous studies, there was no significant difference in the frequency of subjects with HLA-B*1502 between the LTG-induced SJS ⁄ TEN group and the LTG-tolerant group (p = 0.08, OR 4.23, 95% CI 0.94-18.97). In the MPE group, only one was positive for HLA-B*1502. There was no significant difference in the frequency of a specific HLA-B allele between the MPE group and the LTG-tolerant group either. In this study, no significant association between HLA-B*1502 and LTG-induced SJS or MPE was found. Given the small sample size and only HLA-B locus genotyping, further large-scale studies are required to explore genetic associations with LTG-induced cADRs.

Enalaprilat (Ena.), an angiotensin II (Ang II) converting enzyme inhibitor (ACEI), can produce some therapeutic effects on hypertension, ventricular hypertrophy and myocardial remodeling in clinic, but its precise mechanism, especially its signaling pathways remain elusive. In this study, cardiac fibroblasts (CFb) was isolated by the trypsin digestion method; a BrdU proliferation assay was adopted to determine cell proliferation; an immunofluorescence assay was used to measure intracellular reactive oxygen species (ROS); immunocytochemistry staining and Western blotting assay were used to detect phosphorylated p38 mitogen activated protein kinase (p-p38MAPK) and transforming growth factor-β 1 (TGF-β 1 ) protein expression, respectively. The results showed that Ang II (10 -7 M) stimulated the cardiac fibroblast proliferation which was inhibited by NAC (an antioxidant), SB203580 (a p38MAPK inhibitor) or enalaprilat; Ang II caused an burst of intracellular ROS level within thirty minutes, an increase in p-p38MAPK (3.6-fold of that in the control group), as well as an elevation of TGF-β 1 meantime; NAC, an antioxidant, and enalaprilat treatment attenuated cardiac fibroblast proliferation induced by Ang II and decreased ROS and p-p38MAPK protein levels in rat cardiac fibroblast; SB203580 lowered TGF-β 1 protein expression in rats' CFb in a dose-dependent manner. It could be concluded that enalaprilat can inhibit the cardiac fibroblast proliferation induced by Ang II via blocking ROS/P38MAPK/TGF-β 1 signaling pathways and the study provides a theoretical proof for the application of ACEIs in treating OPEN ACCESSMolecules 2012, 17 2739 myocardial fibrosis and discovering the primary mechanism through which ACEIs inhibit CFb proliferation.

Till now truncation mutations of voltage-gated sodium channel alpha subunit type I (SCN1A) gene were mostly found in severe myoclonic epilepsy of infancy (SMEI) patients. In this research we first identified two novel de novo truncation mutations (S662X and M145fx148) in two patients whose phenotypes were quite milder compared with SMEI patients. One patient was diagnosed as generalized epilepsy with febrile seizures plus (GEFS+); the other had focal seizures. Both patients had good response to anti-epileptic therapy (valproate or the combination of valproate and topiramate). Our findings extended the utility of the SCN1A gene testing and further confirmed the complex relationship between genotype and phenotype of SCN1A mutations. Further work is needed to optimize the protocol for specific genetic testing in children with epilepsy.

Communication frequency is increasing with the growing complexity of emerging embedded applications and the number of processors in the implemented multiprocessor SoC architectures. In this article, we consider the issue of communication cost reduction during multithreaded code generation from partitioned Simulink models to help designers in code optimization to improve system performance. We first propose a technique combining message aggregation and communication pipeline methods, which groups communications with the same destinations and sources and parallelizes communication and computation tasks. We also present a method to apply static analysis and dynamic emulation for efficient communication buffer allocation to further reduce synchronization cost and increase processor utilization. The existing cyclic dependency in the mapped model may hinder the effectiveness of the two techniques. We further propose a set of optimizations involving repartition with strongly connected threads to maximize the degree of communication reduction and preprocessing strategies with available delays in the model to reduce the number of communication channels that cannot be optimized. Experimental results demonstrate the advantages of the proposed optimizations with 11-143% throughput improvement.