Study of changes in rs2283265 polymorphisms in dopamine receptor D2 and rs27072 in dopamine transporter gene (SLC6A3) in patients with attention-deficit hyperactivity disorder

ObjectivesAttention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in children that lead to numerous complications. This study examined the changes in rs2283265 polymorphisms in the dopamine receptor D2 (DRD2) and rs27072 in the dopamine transporter gene (SLC6A3) in ADHD patients.Materials & MethodsThis descriptive-analytical study was performed on children aged 4-12 years with ADHD. In this study, 100 patients in the ADHD group (according to DSM-IV-TR criteria and diagnosed by interview by a child and adolescent psychiatrist) and 100 children in the control group (including patients referring to the pediatrician without hyperactivity) were enrolled.Two polymorphisms rs2283265 and rs27072 in two groups were comparatively investigated using PCR-RFLP method and restriction enzymes. Data were analyzed using SPSS 17. ResultsThere was a significant correlation between gender and ADHD, and the disease was more common in boys (P=0.021). In this study, there was no significant relationship between ADHD types and frequency distribution of rs2283265 (DRD2) and rs27072 (SLC6A3) polymorphism genotypes (P<0.05). However, there was a significant correlation between distribution of rs2283265 (DRD2) and rs27072 (SLC6A3) polymorphisms and ADHD (P<0.05). ConclusionIt seems that the changes in DRD2 and SLC6A3 genes are associated with ADHD, and study of these genes can be helpful in diagnosis and genetic screening

Production of High Specific Activity Radioisotopes via the Szilard-Chalmers Method, Using the UC-Irvine TRIGA® Reactor

ABSTRACT OF THE DISSERTATIONProduction of High Specific Activity Radioisotopes via the Szilard-Chalmers Method, Using the UC-Irvine TRIGA® ReactorByLeila Safavi-TehraniDoctor of Philosophy in Chemical and Biochemical EngineeringUniversity of California, Irvine, 2016Professor Mikael Nilsson, Chair Radioactive isotopes have become an important imaging, diagnostic and therapeutic tool in the medical field. For example, the neutron rich samarium isotope of 153Sm has been proven to have desirable characteristics for treatment of bone cancer. However, for medical purposes, the radioisotope must be produced with high specific activity, i.e. low concentration of inactive carrier, so they are beneficial for therapy and the concentration of the metal ions does not exceed the maximum sustainable by the human body. The objective of the research study was to produce radioisotopes, specifically the lanthanides, with increased specific activity in a small-scale research reactor using the Szilard-Chalmers method. The preliminary experimental results showed a decrease of 34% in the amount of Lanthanide needed for a typical medical procedure1. An innovative experimental setup was also developed that instantaneously separated the radioactive recoil product formed during irradiation from the bulk of non-radioactive ions. The instant separation prevented the recoiled radioactive nucleus from reforming its original bonds within the target matrix and chemically separated it from the non-radioactive target matrix, resulting in a radioisotope product with increased specific activity. The novel experimental setup resulted in further improvement of the radiolanthanide enrichment factors, and ultimately resulted in a decrease of 96% in the amount of lanthanide needed for typical medical applications. The methods for preparation and synthesis of the material used for irradiations, the results of enrichment factors and extraction yields in radioactive lanthanide solutions are discussed. The obtained results will be compared to previously published methods and their corresponding results

Production of High Specific Activity Radioisotopes via the Szilard-Chalmers Method, Using the UC-Irvine TRIGA® Reactor

ABSTRACT OF THE DISSERTATIONProduction of High Specific Activity Radioisotopes via the Szilard-Chalmers Method, Using the UC-Irvine TRIGA® ReactorByLeila Safavi-TehraniDoctor of Philosophy in Chemical and Biochemical EngineeringUniversity of California, Irvine, 2016Professor Mikael Nilsson, Chair Radioactive isotopes have become an important imaging, diagnostic and therapeutic tool in the medical field. For example, the neutron rich samarium isotope of 153Sm has been proven to have desirable characteristics for treatment of bone cancer. However, for medical purposes, the radioisotope must be produced with high specific activity, i.e. low concentration of inactive carrier, so they are beneficial for therapy and the concentration of the metal ions does not exceed the maximum sustainable by the human body. The objective of the research study was to produce radioisotopes, specifically the lanthanides, with increased specific activity in a small-scale research reactor using the Szilard-Chalmers method. The preliminary experimental results showed a decrease of 34% in the amount of Lanthanide needed for a typical medical procedure1. An innovative experimental setup was also developed that instantaneously separated the radioactive recoil product formed during irradiation from the bulk of non-radioactive ions. The instant separation prevented the recoiled radioactive nucleus from reforming its original bonds within the target matrix and chemically separated it from the non-radioactive target matrix, resulting in a radioisotope product with increased specific activity. The novel experimental setup resulted in further improvement of the radiolanthanide enrichment factors, and ultimately resulted in a decrease of 96% in the amount of lanthanide needed for typical medical applications. The methods for preparation and synthesis of the material used for irradiations, the results of enrichment factors and extraction yields in radioactive lanthanide solutions are discussed. The obtained results will be compared to previously published methods and their corresponding results

Factors Associated with Treatment Adherence in Children with Attention Deficit Hyperactivity Disorder

Background: Attention deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in children. The aim of this study was to investigate factors related to treatment adherence in children with ADHD. Methods: This cross-sectional study was done in 118 children (aged 6-12 years) with ADHD who have been on medications for at least 6 months. The patients were selected based on the convenience sampling method from those who were referred to child psychiatry clinic. Medication Adherence Report Scale, Belief about Medicines Questionnaire specific version, and Children Symptom Inventory-4 were completed by parents and teachers. Findings: Medication adherence had significant negative correlation with inattention scores on teacher-report forms (r = -0.27, P= 0.003) and poor economic status (P = 0.03). There was a positive correlation between medication adherence and history of psychopharmacological treatment in the family (P = 0.01), and father's education level (P = 0.001). Treatment adherence had no significant correlation with age, gender, comorbid disorders, mother's education, family history of ADHD, medication side effects, or parental concerns and beliefs about the necessity of drug use. Conclusion: The factors found to have a correlation with adherence should be taken in to account by clinicians so that adherence can be improved in their patients

Study of Changes in Rs2283265 Polymorphisms in Dopamine Receptor D2 and Rs27072 in Dopamine Transporter Gene (SLC6A3) in Patients with Attention-deficit Hyperactivity Disorder

Objectives Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in children that lead to numerous complications. This study examined the changes in rs2283265 polymorphisms in the dopamine receptor D2 (DRD2) and rs27072 in the dopamine transporter gene (SLC6A3) in ADHD patients. Materials & Methods This descriptive-analytical study was performed on children aged 4-12 years with ADHD. In this study, 100 patients in the ADHD group (according to DSM-IV-TR criteria and diagnosed by interview by a child and adolescent psychiatrist) and 100 children in the control group (including patients referring to the pediatrician without hyperactivity) were enrolled. Two polymorphisms rs2283265 and rs27072 in two groups were comparatively investigated using PCR-RFLP method and restriction enzymes. Data were analyzed using SPSS 17. Results There was a significant correlation between gender and ADHD, and the disease was more common in boys (P=0.021). In this study, there was no significant relationship between ADHD types and frequency distribution of rs2283265 (DRD2) and rs27072 (SLC6A3) polymorphism genotypes (P<0.05). However, there was a significant correlation between distribution of rs2283265 (DRD2) and rs27072 (SLC6A3) polymorphisms and ADHD (P<0.05). Conclusion It seems that the changes in DRD2 and SLC6A3 genes are associated with ADHD, and study of these genes can be helpful in diagnosis and genetic screening

Novel quinazolin-4(3H)-one linked to 1,2,3-triazoles: Synthesis and anticancer activity

In this work, a wide range of novel quinazolin-4(3H)-one linked to 1,2,3-triazoles was designed, synthesized, and evaluated against a panel of three human breast (MDA-MB-231, MCF-7, T-47D), lung (A549), and prostate (PC3) cancer cell lines. Our results revealed that the anticancer activity of the synthesized compounds was selectively affected by the presence of methoxy group on the linker between quinazolinone and 1,2,3-triazole moieties. According to the calculated IC50 values, compounds 6q, 6w, and 6x showed good cytotoxicity against breast cancer cell lines even more effective than the reference drug, etoposide. Compounds 6q and 6u were found to be potent compounds against A549, non-small-cell lung cancer (NSCLC), comparing with erlotinib. Also, the morphological analysis by acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that potent compounds induced apoptosis in human cancer cell lines. Molecular docking studies were performed to clarify the inhibition mode of compounds 6g, 6u, 6w, and 6x over the EGFR active site. The most promising compounds, 6q and 6u, possessing 3-methoxy group were well oriented to the gatekeeper hydrophobic pocket of EGFR active site and interact well with Ala719, Val702, and Leu820 through hydrophobic interaction. © 2018 John Wiley & Sons A/S