Lower Erythrocyte GST activity in Autism Spectrum Disorder (ASD) patients compared to normal controls

Glutathione S-transferases (GST) are antioxidant enzymes that play an important role in the cellular detoxification and excretion of environmental pollutants including heavy metals. GST mu (GSTM1) and G theta (GSTT1) are known to be highly polymorphic and homozygous deletions of these genes result in the lack of enzyme activity and when combined with decreased levels of antioxidants, they have been associated with the Autism Spectrum Disorder (ASD). This preliminary study was performed to investigate the role of GSTM1 and GSTT1 polymorphisms as risk factors of ASD associated with GST activity and phenotype expression. Fifty one ASD patients and 45 controls were recruited for GSTM1 and GSTT1 genotyping while 6 ASD patients and 8 controls were assessed for GST activity. The results showed no significant differences in frequencies of GSTM1 null, GSTT1 null and combination both genotype between ASD patients and controls. However the mean erythrocyte GST activity in ASD is significantly decreased compared with controls (p = 0.043). The mean erythrocyte GST activity is lower in the severely autistic group compare to the mild to moderately autistic group, although it was not statistically significant. Further investigations are needed with a bigger sample size, analyzing multiple GST genes and GST activity determination to find out the gene susceptibility of ASD and factors that contribute to the phenotype expression of ASD

Screening for HLA-B*1502 Polymorphism in Febrile Seizure Predicted Lead to Epilepsy

Mutation in neuronal sodium channel -1-subunit gene (SCN1A) and neuronal sodium channel -1-subunit gene (SCN1B) has been linked with forms of generalized epilepsy with febrile seizure plus (GEFS+) and epileptic infantile syndrome like severe myoclonic epilepsy of infancy (SMEI) (Mulley et al., 2005; Scheffer et al., 2007). Since this idiopathic epilepsy typically begins with prolonged febrile seizures (FS) in the first year of life, therefore febrile seizure patient with mutation in SCN1A has a high risk to develop epilepsy on their later life (Dube et al., 2009). Carbamazepine (CBZ) has been known as the most common anti-epileptic drug which can cause Steven-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients with HLA-B*1502 polymorphism. Since the Javanese population have 16,67% of these allele, studying the presence of these allele in patients predicted epilepsy is important. Furthermore, this study was intended to develop a PCR-based diagnostic protocol to screen HLA-B*1502 polymorphism in epileptic patients to prevent SJS/TEN by carbamazepine. Focusing on epileptic predicted patients, HLA-B*1502 genotyping by sequence specific primer (SSP)-PCR was performed on 31 repeated FS patients with mutation in SCN1A and SCN1A/SCN1B gene. The result show that the HLA-B*1502 polymorphism was detected in 14 (45,2%) individuals including 8 cases related to mutation SCN1A gene and 6 to SCN1A/SCN1B gene. It illustrates that HLA-B*1502 allele is frequent in these patients. It can thus be suggested that detection of this allele should be done before epilepsy treatment. Later, patients with this allele should avoid CBZ to prevent SJS/TEN during drug administration

The inflammatory microenvironment in colorectal neoplasia

Peer reviewedPublisher PD

Curcumin Alleviates Matrix Metalloproteinase-3 and -9 Activities during Eradication of Helicobacter pylori Infection in Cultured Cells and Mice

Current therapy-regimens against Helicobacter pylori (Hp) infections have considerable failure rates and adverse side effects that urge the quest for an effective alternative therapy. We have shown that curcumin is capable of eradicating Hp-infection in mice. Here we examine the mechanism by which curcumin protects Hp infection in cultured cells and mice. Since, MMP-3 and -9 are inflammatory molecules associated to the pathogenesis of Hp-infection, we investigated the role of curcumin on inflammatory MMPs as well as proinflammatory molecules. Curcumin dose dependently suppressed MMP-3 and -9 expression in Hp infected human gastric epithelial (AGS) cells. Consistently, Hp-eradication by curcumin-therapy involved significant downregulation of MMP-3 and -9 activities and expression in both cytotoxic associated gene (cag)+ve and cag-ve Hp-infected mouse gastric tissues. Moreover, we demonstrate that the conventional triple therapy (TT) alleviated MMP-3 and -9 activities less efficiently than curcumin and curcumin's action on MMPs was linked to decreased pro-inflammatory molecules and activator protein-1 activation in Hp-infected gastric tissues. Although both curcumin and TT were associated with MMP-3 and -9 downregulation during Hp-eradication, but unlike TT, curcumin enhanced peroxisome proliferator-activated receptor-γ and inhibitor of kappa B-α. These data indicate that curcumin-mediated healing of Hp-infection involves regulation of MMP-3 and -9 activities