Neuroprotective effect of Allium cepa L. in aluminium chloride induced neurotoxicity

The present study was envisaged to investigate the neuroprotective potential of Allium cepa (A. cepa) in aluminium chloride induced neurotoxicity. Aluminium chloride (50 mg/kg/day) was administered orally in mice supplemented with different doses of A. cepa hydroethanolic extract for a period of 60 days. Various behavioural, biochemical and histopathological parameters were estimated in aluminium exposed animals. Chronic aluminium administration resulted in significant motor incoordination and memory deficits, which were also endorsed biochemically as there was increased oxidative stress as well as elevated acetylcholinesterase (AChE) and aluminium levels in the brain. Supplementation with A. cepa in aluminium exposed animals significantly improved muscle coordination and memory deficits as well as reduced oxidative stress, AChE and decreased abnormal aluminium deposition in the brain. Histopathologically, there was marked deterioration visualized as decreased vacuolated cytoplasm as well as decreased pyramidal cells in the hippocampal area of mice brain which were found to be reversed with A. cepa supplementation. Administration of BADGE (PPARγ antagonist) in aluminium exposed animals reversed the neuroprotective potential of A. cepa as assessed with various behavioural, biochemical, neurochemical and histopathological estimations. In conclusion, finding of this study suggested significant neuroprotective potential of A. cepa in aluminium induced neurotoxicity. Further, the role of PPARγ receptor agonism has also been suggested as a putative neuroprotective mechanism of A. cepa, which needs further studies for confirmation.     

Two neighboring microdeletions of 5q13.2 in a child with oculo-auriculo-vertebral spectrum

We describe a patient with multiple congenital anomalies, including hemifacial microsomia, asymmetric macrostomia, dysplastic mandible, multiple preauricular tags, atresia of the external auricular canal, and vertebral anomalies, which coincide with oculo-auriculo-vertebral spectrum. G-banding (～850 band level) showed a normal 46, XY karyotype. A genome-wide screen for copy number variations (CNVs) using single nucleotide polymorphism (SNP) arrays revealed a 1 Mb and a 167 kb deletion both on chromosome 5q13.2, which were absent in the parents and in 27 controls. Sixteen genes were located in the deleted region, including BIR1C and OCLN, which are involved in apoptosis. Haploinsufficiency of these genes may be contributing to the phenotype in this patient. To our knowledge, there are no previous reports of this 5q13.2 deletion in a patient with oculo-auriculo-vertebral spectrum.     

Rapid and reliable β-globin gene cluster haplotyping of sickle cell disease patients by FRET Light Cycler and HRM assays

Backgroundβ-Globin haplotypes are important to predict the clinical development of patients suffering from sickle cell disease (SCD). Five main haplotypes (Benin, Bantu, Senegal, Cameroon and Arabic–Indian) are defined for β^S chromosomes and their determination usually requires the genotyping by restriction fragment length polymorphism (RFLP) of six to eight single nucleotide polymorphisms (SNPs). However, RFLP is time-consuming and can lead to a misdiagnosis in case of a supplementary SNP on the restriction sequence. We propose a rapid β-globin haplotyping method using fluorescence resonance transfer (FRET) and high resolution melting (HRM) assays.MethodsWe have settled a fluorescence resonance energy transfer (FRET) assay for HincII ε, XmnI, HindIII ^Gγ, HindIII ^Aγ, HincII δ and a high resolution melting (HRM) assay for HincII ψβ. These six SNPs are sufficient in most cases to determine the β^S haplotype.ResultsOur methodology allowed us to successfully determine the β-globin haplotypes of 139 patients suffering from sickle cell disease. For some β^S / β⁰-patients, a supplementary SNP has been identified on the HindIII ^Gγ restriction sequence leading to a false-negative RFLP result.ConclusionCombination of FRET and HRM assays is a rapid and reliable method for the β-globin gene cluster haplotyping.     

Association Between Toll-like Receptors 4 and 2 Gene Polymorphisms With Chronic Allograft Nephropathy in Turkish Children

Toll-like receptor (TLR) gene polymorphism is known to impair intracellular signaling pathways following adaptive immune responses. Our aim was to investigate the distribution of TLR4 and TLR2 gene polymorphisms among pediatric renal transplantation patients in relation to chronic allograft nephropathy (CAN). In addition to 115 healthy controls, we included 69 renal recipients, 19 of whom were identified as CAN by biopsy scored according to the Banff criteria. Polymorphisms at TLR4 Asp299Gly and/or Thr399Ile were present in 11.6% of renal transplant recipients. None of these subjects was identified in cosegregation with the Thr399Ile allele, whereas three had an isolated Asp299Gly and five had an isolated Thr399Ile. Neither renal recipients nor healthy controls were homozygous for both Asp299Gly and Thr399Ile polymorphisms. However, TLR4 Thr399Ile polymorphism and Ile allele was greater among CAN (?) versus CAN (+) recipients (P > .05). The frequency of TLR2 mutant type Gln allele was significantly higher in recipients than among healthy controls (P < .0001). However, the Gln allele frequency was similar between CAN (+) and CAN (?) patients. The results of present study may be speculated to show TLR4 and TLR2 gene polymorphisms as protective factors from CAN development due to impaired immune responses.