Age and ApoE genotype interaction in Alzheimer's disease: an FDG-PET study

Previous positron emission tomography (PET) studies with fluorodeoxglucose (FDG) as tracer in healthy elders showed that the epsilon4 allele of the apolipoprotein E (ApoE) gene is disruptive to cerebral glucose metabolism (rCMRglu), possibly through the interaction with the aging process. The present study was aimed at assessing whether this interaction occurs in patients with Alzheimer's disease (AD). Eight-six AD patients, including 40 ApoE4 carriers and 46 non-carriers, underwent (18)F-FDG PET scanning at rest. ApoE groups were comparable for age, gender, age at onset and disease duration. SPM'99 was used to assess rCMRGlu correlations with age, differences between ApoE groups and ApoE by age interaction, correcting for disease severity. Results were reported at P<0.001, uncorrected. Correlations between age and rCMRGlu confirmed the well-known negative relationship for both groups. Lower rCMRGlu was found within the frontal and cingulate areas for ApoE4 carriers as compared with the non-carriers. Additionally, a significant ApoE by age interaction was detected in the frontal and anterior cingulate cortex, with the ApoE4 carriers having a steeper regression slope with respect to the non-carriers. These results indicate that age-related regional rCMRglu decreases within the frontal and anterior cingulate areas may be more severe in AD patients carrying the ApoE4 allele.     

Evaluation of polycyclic aromatic hydrocarbons (PAHs) in fish: a review and meta-analysis

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are a group of pollutants which occur in considerable amounts in the environment and food. In this study, a meta-analysis study was conducted on PAHs concentrations in fish in different parts of the world. The results showed that the PAHs were observed and quantified in fish in the most considered studies. The maximum and minimum concentration of PAHs was found in Cynoglossus Bilineatus fish of Persian Gulf (3970?ng/kg) and Cyprinus Carpio fish of Caspian Sea (0.004?ng/kg), respectively. These values are below the maximum value currently allowed by European Union regulations (12.0?μg/kg wet weight).     

Nonsense mediated decay of VWF mRNA subsequent to c.7674-7675insC mutation in type3 VWD patients

Von Willebrand disease (VWD), the most common genetic bleeding disorder, is caused by defects in Von Willebrand factor (VWF). Quantitative deficiencies of the protein lead to either VWD type3, the severe form of the disease or VWD type1 with milder clinical manifestation. Null alleles are the most common mutations in VWF gene causing type3. However, some of these mutations are not translated into the protein and are selectively degraded at mRNA level by nonsense-mediated decay (NMD) pathway. Here, we have studied a large VWD type3 pedigree with a premature termination codon (PTC) causing insertion mutation (c.7674-7675insC) in VWF exon 45. We further investigated the impact of the mutation on the VWF mRNA expression using a quantitative Real-time PCR assay and cDNA sequencing. The relative expression of the gene was significantly decreased in the patients' platelets (Mean ratio=0.03 (0.01-0.05), p=0.001) compared to their normal relatives. The heterozygote carriers of the mutation had lower than normal VWF mRNA levels (Mean ratio=0.62 (0.29-0.91), p=0.006). Direct sequencing of exon 45 on the platelet-derived cDNA in the carriers revealed only the wild-type allele confirming the decay of the mutation carrying allele. In conclusion, quantitative analysis of VWF gene expression showed that c.7674-7675insC mutation in VWF gene resulted in degradation of VWF mRNA via NMD. This pathway might play an important role in the pathogenesis of VWD characterized by quantitative deficiency of VWF due to reduced mRNA levels.     

The dynamics of metabolic syndrome development from its isolated components among iranian children and adolescents: Findings from 17 Years of the Tehran Lipid and Glucose Study (TLGS)

BackgroundCareful evaluation of the progression trend of the metabolic syndrome (MetS) in children and adolescents (C&A) is one of the important methods of studying the natural history of MetS in them. This study was performed to determine the trend of changes in the progression of MetS from its components.MethodsThis was a longitudinal study which was performed on data from 4 follow-up periods of Tehran Lipid and Glucose Study (TLGS) between 1999 and 2015. The research population consisted of 6-18-year-old children and adolescents creating 3895-person population. The criteria for the diagnosis of MetS was joint interim statement (JIS). The considered components were central adiposity, high blood pressure, insulin resistance, and dyslipidemia.ResultsIn this study, in the long term, the highest increase in the MetS’ incidence in boys occurred in obesity and in girls in dyslipidemia and in total mode, in obesity. But in the short term (3.6 year follow-up periods) in the first to fourth periods, in total mode, the highest incidence occurred in dyslipidemia, hyperglycemia, dyslipidemia, and obesity. In terms of trend, in total mode, the highest increase in MetS incidence was related to the obesity component. Also, the incidence of MetS from all components was declining in overall mode. Also, the most common components at the beginning and end of the study in all groups were dyslipidemia with a decreasing and obesity with an increasing trend, respectively.ConclusionIt seems that in Iranian C&As, obesity and dyslipidemia components play a more important role in the further development of the MetS than other components. This matter requires careful and serious attention in preventive and control planning.     

Protective effect of melatonin in the diabetic rat retina

Diabetic retinopathy (DR) is one of the most common and serious microvascular complications of diabetes. The aim of this study was to evaluate the effects of melatonin (MEL) on retinal injury in diabetic rats. In this study, 21 rats were randomly divided into three groups: control, diabetic, and diabetic + MEL. Streptozotocin was used to induce diabetes at a dose of 50 mg/kg, i.p., and blood glucose was measured to choose the diabetic rats for the study. MEL (20 mg/kg) was given orally for 7 weeks in diabetic rats starting 1 week after induction of diabetes. After 8 weeks, the groups were compared in terms of mean scores of fluorescein leakage, using fluorescein angiography. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels were estimated in retina using commercially available assays. Structural changes in retinas were evaluated by light microscopy. Results showed that diabetes significantly increased the mean scores of fluorescein leakage, and MDA and ROS levels compared to control group. Treatment of the diabetic rats with MEL for 7 weeks prevented the alterations induced by diabetes in comparison with the diabetic control group.Based on these findings, it can be concluded that MEL might have beneficial effects in prevention of DR.     

A Dermal Equivalent Engineered with TGF‐β3 Expressing Bone Marrow Stromal Cells and Amniotic Membrane: Cosmetic Healing of Full‐Thickness Skin Wounds in Rats

Transforming growth factor beta‐3 (TGF‐β3) has been shown to decrease scar formation after scheduled topical applications to the cutaneous wounds. This study aimed to continuously deliver TGF‐β3, during the early phase of wound healing, by engineering a dermal equivalent (DE) using TGF‐β3 expressing bone marrow stromal cells (BM‐SCs) and human dehydrated amniotic membrane (hDAM). To engineer a DE, rat BM‐SCs were seeded on the hDAM and TGF‐β3 was transiently transfected into the BM‐SCs using a plasmid vector. Pieces of the dermal equivalent were transplanted onto the full‐thickness excisional skin wounds in rats. The process of wound healing was assessed by image analysis, Manchester Scar Scale (MSS), and histopathological studies 7, 14, 21, and 85 days after the excision. The results confirmed accurate construction of recombinant pcDNA3.1‐TGF‐β3 expression system and showed that the transfected BM‐SCs seeded on hDAM expressed TGF‐β3 mRNA and protein from day 3 through day 7 after transfection. After implantation of the DE, contraction of the wounds was measured from day 7 through 21 and analyzed by linear regression, which revealed that the rate of wound contraction in all experimental groups was similar. Histologic evaluation demonstrated that transfected BM‐SCs decreased retention and recruitment of the cells during the early stage of wound healing, decreased the formation of vascular structures and led to formation of uniformly parallel collagen bundles. MSS scores showed that TGF‐β3 secreting cells significantly improved the cosmetic appearance of the healed skin and decreased the scar formation. From these results, it could be concluded that transient secretion of TGF‐β3, during the early phase of healing, by BM‐SCs seeded on hDAM can improve the cosmetic appearance of the scar in cutaneous wounds without negatively affecting the process of wound repair.