Effects of empowerment program on the burden of care in mothers of children with phenylketonuria

Objectives: Phenylketonuria (PKU) is a genetic disease of children that need a lifelong diet for its treatment. Because of the high burden of care, Parents and particularly mothers are prone to mental disorders or psychiatric adverse reactions. This study aimed to investigate the effect of empowerment of mothers on the burden of caring children with phenylketonuria.Materials & Methods: This was a semi-experimental (before-after with control group) study. In this research, 50 mothers of children with phenylketonuria that were referred to endocrine clinic in Qods hospital of Qazvin city, were selected and randomly divided into intervention and control groups. Data collection was made by using demographic characteristics of mothers and children and also the Zarit burden interview questionnaires. Empowerment program was delivered during nine sessions of holistic and family oriented empowerment model in the intervention group.  The control group received routine services. Data were analyzed using descriptive and inferential statistics through SPSS software version 18.Results: In intervention group, the mean score of overall care burden and its dimensions in the mothers of children with phenylketonuria in post-test was significantly lower than the pre-test  (41.20 ± 5.04 vs. 58.24 ± 3.96; p<0. 001); but  pre-test and post-test scores in the control group had no significant difference (58.4 ± 5.22 vs. 58.96 ± 4; p=0.327). In other words empowerment program was able to reduce the burden of caring in mothers.Conclusion: Empowerment program can reduce the burden of care in mothers of children with phenylketonuria. Thus it seems that empowerment training is necessary to this group of mothers in the form of workshops and educational pamphlets

The Effect of Iron on Malignant Lymphoblastic Cells Survival and Its Mechanism

Background and Objectives:Anemia is a common complication of chemotherapy. In order to resolve this problem, multiple red blood cell transfusions are administered, leading to iron overload. Given the confirmation of positive correlation between the increased bone marrow iron stores and adverse response to the treatment in the previous study, the effect of iron on the proliferation of acute lymphoblastic leukemia (ALL) cell lines cell lines and its underlying mechanism were investigated in the current study.   Methods:Nalm6 and CCRF-CEM cell lines were selected as representatives of B-ALL and T-ALL Immunophenotypes and were treated with different concentrations of holo-transferrin (1 - 120 µM) and ferric ammonium citrate (FAC) (400 - 25000 µM). The cellular iron uptake was confirmed by AAS test. The cell proliferation and levels of intracellular free radicals (ROS), were evaluated by MTT and flow cytometry, respectively. Statistical analysis was performed using GraphPad prism software by one-way ANOVA test.   Results: The effect of holo-transferrinon cell proliferation was not significant. However, FAC enhanced the proliferation rate of both ALL cell lines over 50%. Evidence showed that iron induced intracellular ROS, so that FAC in the concentration of 400 µM may induce the intracellular ROS over 50% (55.27 6 6.36% vs. 100%, p < 0.001).   Conclusion: Iron can support these cancerous cells by inducing ROS and augmenting leukemic cell proliferation. Therefore, the present study suggests that the volume of the injected blood in ALL patients should be minimized to prevent iron overloa

ABCC4 functional SNP in the 3' splice acceptor site of exon 8 (G912T) is associated with unfavorable clinical outcome in children with acute lymphoblastic leukemia

Objectives ATP-binding cassette subfamily C member 4 (ABCC4) encoding MRP4 protein is involved in pediatric acute lymphoblastic leukemia (ALL) drug resistance. The nonsynonymous single nucleotide polymorphism (SNP) rs2274407 (G912T; K304N) is located in the 3′ splice acceptor site of exon 8 of ABCC4 pre-mRNA. The aim of this study was to investigate the prognostic value of rs2274407 in childhood ALL and its possible functional effect on MRP4. Methods ABCC4 G912T SNP was genotyped in 145 Iranian Philadelphia-negative (Ph−) children with ALL using modified tetra-primer ARMS PCR and evaluated for possible association with 3-year disease-free survival (3DFS). In addition, functional impact of rs2274407 on the MRP4 activity and possible post-transcriptional modifications were bioinformatically and experimentally studied. Results ABCC4 912T allele carriers (G/T and T/T genotypes) are associated with worse 3DFS in Pre-B cell ALL [P = 0.00019, OR (95% CI) = 13.17 (2.55–68.11)]. In addition, computational studies showed that K304N alteration has no impact on the MRP4 activity. However, it may disrupt the normal splicing process of ABCC4 pre-mRNA. Conclusions To date, this is the first study that shows the potential functional impact of rs2274407 SNP on the aberrant splicing of ABCC4 mRNA. We also demonstrated a robust association between G912T and pediatric ALL negative outcome, which may be explained by the novel computational studies performed in this study

The antitoxic effects of quercetin and quercetin-conjugated iron oxide nanoparticles (QNPs) against H2O2-induced toxicity in PC12 cells

Background: We recently showed that quercetin-conjugated iron oxide nanoparticles (QNPs) promoted the bioavailability of quercetin (Qu) in the brain of rats and improved the learning and memory of diabetic rats. In this study, we characterized the modifications in the antitoxic effects of Qu after conjugation. Materials and methods: We conjugated Qu to dextran-coated iron oxide nanoparticles (DNPs) and characterized DNPs and QNPs using FTIR, XRD, DLS, Fe-SEM, and EDX analyzes. The antiradical properties of Qu, DNPs, and QNPs were compared by 2, 2-diphenyl- 1-picrylhydrazyl (DPPH) scavenging activity assay. Catalase-like activities of DNPs and QNPs were estimated using catalase activity assay kit, and the antitoxic effects of Qu and QNPs were evaluated with spectrophotometry, MTT assay, flow cytometry, and real-time q-PCR. Results: Qu had a stronger anti-radical activity than DNPs and its activity decreased after being conjugated to DNPs. The catalase-like activity of DNPs remained intact after conjugation. DNPs had less toxicity on PC12 cells viabilities as compared to free Qu, and the conjugation of Qu with DNPs attenuated its cytotoxicity. Furthermore, MTT assay results indicated 24 h pretreatment with Qu had more protective effects than QNPs against H2O2- induced cytotoxicity, while Qu and QNPs had the same effects for 48 and 72 h incubation. Although the total antioxidant capacity of Qu was attenuated after conjugation, the results of flow cytometry and real-time q-PCR confirmed that 24 h pretreatment with the low concentrations of Qu and QNPs had the similar antioxidant, anti-inflammatory, and antiapoptotic effects against the cytotoxicity of H2O2. Conclusion: Qu and QNPs showed the similar protective activities against H2O2-induced toxicity in PC12 cells. Given the fact that QNPs have magnetic properties, they may serve as suitable carriers to be used in neural research and treatment

Iron oxide nanoparticles may damage to the neural tissue through iron accumulation, oxidative stress, and protein aggregation

Abstract Background In the recent decade, iron oxide nanoparticles (IONPs) have been proposed for several applications in the central nervous system (CNS), including targeting amyloid beta (Aβ) in the arteries, inhibiting the microglial cells, delivering drugs, and increasing contrast in magnetic resonance imaging. Conversely, a notable number of studies have reported the role of iron in neurodegenerative diseases. Therefore, this study has reviewed the recent studies to determine whether IONPs iron can threaten the cellular viability same as iron. Results Iron contributes in Fenton’s reaction and produces reactive oxygen species (ROS). ROS cause to damage the macromolecules and organelles of the cell via oxidative stress. Iron accumulation and oxidative stress are able to aggregate some proteins, including Aβ and α-synuclein, which play a critical role in Alzheimer’s and Parkinson’s diseases, respectively. Iron accumulation, oxidative stress, and protein aggregation make a positive feedback loop, which can be toxic for the cell. The release of iron ions from IONPs may result in iron accumulation in the targeted tissue, and thus, activate the positive feedback loop. However, the levels of IONPs induced toxicity depend on the size, concentration, surface charge, and the type of coating and functional groups of IONPs. Conclusion IONPs depending on their properties can lead to iron accumulation, oxidative stress and protein aggregation in the neural cells. Therefore, in order to apply IONPs in the CNS, the consideration of IONPs properties is crucial

Studies on beta 2 glycoprotein I and antiphospholipid antibodies

Beta 2 glycoprotein I (&#946;2GPI) is a major antigenic target in antiphospholipid syndrome (APS). In vitro studies suggest that it may have multifaceted physiological functions, as it displays both anticoagulant and procoagulant properties. Beta 2GPI may bind to FXI and serve as a regulator of FXI activation by thrombin. The possible interaction of &#946;2GPI with thrombin is investigated using enzyme linked immunosorbent assays and surface plasmon resonance based studies. It is demonstrated for the first time that domain V of &#946;2GPI is involved in direct binding to thrombin, and exosites I and II on thrombin take part in this interaction. It is also shown that cleavage of &#946;2GPI at Lys317-Thr318 does not interrupt this binding. A quaternary complex is proposed on the surface of activated platelets in which &#946;2GPI may colocalise with FXI and thrombin to regulate FXIa generation. The effect of anti-&#946;2GPI monoclonal antibodies (mAbs) were investigated on this system using 8 anti-&#946;2GPI mAbs directed against domain I. Anti-&#946;2GPI Abs potentiate the suppressing activity of &#946;2GPI on FXI activation by thrombin. Moreover, they restore the inhibitory effect of clipped &#946;2GPI on this system. The current study demonstrates for the first time a novel biological consequence of thrombin interaction with &#946;2GPI. The effect of &#946;2GPI on thrombin inactivation by the serine protease inhibitor heparin cofactor II (HCII) is investigated using chromogenic assays, platelet aggregation studies, and the platelet release response. The current work shows that &#946;2GPI protects thrombin from inactivation by HCII/Heparin. This ability is modulated by the cleavage of &#946;2GPI. A ternary structure is proposed between &#946;2GPI, thrombin and heparin which may limit the N-terminus of HCII to exosite I therefore inhibit thrombin inactivation by HCII. The effect of anti-&#946;2GPI Abs is examined in this system using patient polyclonal IgGs and a murine anti-&#946;2GPI mAb. Anti-&#946;2GPI Abs potentiate the protective effect of &#946;2GPI on thrombin inhibition by HCII/Heparin. In view of the importance of HCII in regulating thrombin activity within the arterial wall, disruption of this function by &#946;2GPI/anti-&#946;2GPI Ab complexes may be particularly relevant in arterial thrombosis in APS.Beta 2 glycoprotein I (&#946;2GPI) is a major antigenic target in antiphospholipid syndrome (APS). In vitro studies suggest that it may have multifaceted physiological functions, as it displays both anticoagulant and procoagulant properties. Beta 2GPI may bind to FXI and serve as a regulator of FXI activation by thrombin. The possible interaction of &#946;2GPI with thrombin is investigated using enzyme linked immunosorbent assays and surface plasmon resonance based studies. It is demonstrated for the first time that domain V of &#946;2GPI is involved in direct binding to thrombin, and exosites I and II on thrombin take part in this interaction. It is also shown that cleavage of &#946;2GPI at Lys317-Thr318 does not interrupt this binding. A quaternary complex is proposed on the surface of activated platelets in which &#946;2GPI may colocalise with FXI and thrombin to regulate FXIa generation. The effect of anti-&#946;2GPI monoclonal antibodies (mAbs) were investigated on this system using 8 anti-&#946;2GPI mAbs directed against domain I. Anti-&#946;2GPI Abs potentiate the suppressing activity of &#946;2GPI on FXI activation by thrombin. Moreover, they restore the inhibitory effect of clipped &#946;2GPI on this system. The current study demonstrates for the first time a novel biological consequence of thrombin interaction with &#946;2GPI. The effect of &#946;2GPI on thrombin inactivation by the serine protease inhibitor heparin cofactor II (HCII) is investigated using chromogenic assays, platelet aggregation studies, and the platelet release response. The current work shows that &#946;2GPI protects thrombin from inactivation by HCII/Heparin. This ability is modulated by the cleavage of &#946;2GPI. A ternary structure is proposed between &#946;2GPI, thrombin and heparin which may limit the N-terminus of HCII to exosite I therefore inhibit thrombin inactivation by HCII. The effect of anti-&#946;2GPI Abs is examined in this system using patient polyclonal IgGs and a murine anti-&#946;2GPI mAb. Anti-&#946;2GPI Abs potentiate the protective effect of &#946;2GPI on thrombin inhibition by HCII/Heparin. In view of the importance of HCII in regulating thrombin activity within the arterial wall, disruption of this function by &#946;2GPI/anti-&#946;2GPI Ab complexes may be particularly relevant in arterial thrombosis in APS

Evaluation of rs62527607 [GT] single nucleotide polymorphism located in BAALC gene in children with acute leukemia using mismatch PCR-RFLP

Acute leukemia is the most common cancer in children and involves several factors that contribute to the development of multidrug resistance and treatment failure. According to our recent studies, the BAALC gene is identified to have high mRNA expression levels in childhood acute lymphoblastic leukemia (ALL) and those with multidrug resistance. Several polymorphisms are associated with the expression of this gene. To date, there has been no study on the rs62527607 [GT] single nucleotide polymorphism (SNP) of BAALC gene and its link with childhood acute lymphoblastic and myeloid leukemia (AML). The purpose of this study is to evaluate the prevalence of this polymorphism in pediatric acute leukemia, as well as its relationship with prognosis. DNA samples were extracted from bone marrow slides of 129 children with ALL and 16 children with AML. The rs62527607 [GT] SNP was evaluated using mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based analysis. The association between the SNP alleles and patient disease-free survival was then assessed. The prevalence of the T-allele of rs62527607 [GT] SNP in childhood T-ALL and pre-B-ALL was 28.3% and 11.2%, respectively. In the pre-B-ALL patients, 3 year disease free survival was associated with the GG genotype. Results showed a robust association between the rs62527607 SNP and the risk of relapse in ALL, but not AML, patients. T-ALL patients with the GT genotype had an 8.75 fold higher risk of relapse. The current study demonstrates a significant association between the genotype GT and the polymorphic allele G424T, and introduces this SNP as a negative prognostic factor in children with ALL

Beta2-Glycoprotein I Binds Thrombin via Exosite I and Exosite II

Objective. Beta2-glycoprotein I (B2GPI) is a dominant antigenic target in antiphospholipid syndrome (APS). Beta2-glycoprotein I may bind to factor XI and serve a physiologic function as a regulator of factor XI activation by thrombin. We undertook this study to investigate the possible interactions of B2GPI with thrombin in B2GPI-regulated factor XI activation by thrombin and to evaluate the effect of anti-B2GPI antibodies on this system. Methods. The B2GPI interaction with thrombin was investigated in direct and competitive assays using B2GPI domain mutants and thrombin-binding exosite oligonucleotides. Beta2-glycoprotein I inhibition of thrombin-mediated factor XI activation was assessed in the presence of 8 anti-B2GPI monoclonal antibodies (mAb) directed against domain I. Results. Domain V of B2GPI was involved in direct binding to thrombin, and exosite I and exosite II on thrombin took part in this interaction. Anti-B2GPI mAb produced a \u3e70% inhibition of thrombin-mediated factor XI activation in the presence of B2GPI