Cardiovascular Considerations in Antidepressant Use

en Cardiovascular Considerations in Antidepressant Use <div style="text-align:justify">Depressive disorders are among the most prevalent disorders worldwide. About 1 in every 5 people experience an episode of depression in their lifetime (1,2). Therefore, antidepressants are among the most frequently prescribed medications worldwide. An analysis of a primary care database in the United Kingdom revealed that 23% of patients were ordered to take antidepressants at least once over the course of 17 years (1995-2011) (3). Antidepressants are categorized into some major groups: 1. Selective Serotonin Reuptake Inhibitors (SSRIs) such as sertraline, fluoxetine, citalopram and escitalopram, 2. Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) such as duloxetine and venlafaxine, 3. Tricyclic Antidepressants (TCAs) such as amitriptyline and nortriptyline, 4. Monoamine oxidase inhibitors (MAOIs) such as selegiline and 5. Atypical antidepressants such as bupropion and mirtazapine. Despite the production of newer antidepressants, patients taking these medications still experience some cardiovascular adverse effects.</div> One of the most well-known cardiovascular adverse effects of antidepressants is QT-prolonging. QT-prolonging can lead to fatal ventricular arrhythmias like Torsades de pointes (TdP) and precipitate sudden death. In 2011, the US Food and Drug Administration (FDA) cautioned healthcare professionals about QT-prolongation associated with high doses of citalopram (4). This encouraged various research groups to examine the safety of other antidepressants with respect to QT interval. Studies manifest that while TCAs are not associated with sudden death unless at higher doses; SSRIs are associated with a higher risk of sudden death specifically in adults with cardiovascular comorbidities (5). A meta-analysis revealed that among SSRIs, significant QT prolongations have been demonstrated in using citalopram and escitalopram; whereas fluoxetine, fluvoxamine, and sertraline did not show a clinically significant increase in QT interval at conventional doses in the majority of the studies (6). On the other hand, paroxetine monotherapy showed no QT prolongation in any of the studies (6-8). While SSRIs are mostly accused of causing QT prolongation; the most common cardiovascular complications caused by high doses of TCA are sinus tachycardia and hypotension (9,10). Sinus tachycardia, seen in 52% of cases with TCA overdose (11), is a result of anticholinergic activity and norepinephrine uptake inhibition by TCAs. Hypotension, on the other hand, happens due to a combination of depressed myocardial contractility and decreased resistance of blood vessels caused by a-adrenergic blockage (10). In contrast to TCAs, SNRIs like venlafaxine can cause hypertension. A pooled analysis of controlled studies showed that while venlafaxine has a low risk of causing clinically significant hypertension at doses <200 mg/day; 5.5% of patients using doses >200 mg/day show significant increases in blood pressure (12). Another issue to be considered is the possibility of cardiovascular birth defects caused by maternal exposure to antidepressants during pregnancy. Maternal exposure to antidepressants 3 months prior to pregnancy or during early pregnancy increases the risk of congenital heart diseases in the newborn (13). A study by Gao et al indicated that newborns with intrauterine exposure to fluoxetine are at a greater risk for cardiovascular defects, especially septal defects(14). Persistent Pulmonary Hypertension of the Newborn (PPHN) is another complication caused by maternal SSRI exposure. research has shown higher rates of PPHN among infants who had intrauterine exposure to SSRIs (15); however, sertraline was proven to be the safest SSRI in this regard (16). Despite the facts regarding mentioned side effects, there are some evidence showing that antidepressants can be beneficial for the cardiovascular system in some manners. SSRIs are manifested to improve endothelial function, vascular inflammation, arterial stiffening and perhaps delaying atherosclerotic events (17,18). Moreover, antidepressant therapy was associated with lower odds of recurrent Myocardial Infarction (MI) in patients with acute coronary syndrome and concomitant depression (19). With those being said, it is crucial not to deprive depressed patients of their adequate drug therapy and to modify their medications based on cardiovascular safety along with the optimal efficacy of the drug. 207 208 https://www.ajmb.org/En/Article.aspx?id=60551 https://www.ajmb.org/PDF/En/FullText/60551.pdf FatemeTaghaviZanjani Department of Cardiology, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran92085SaeedNateghi92086

en Radiotherapy Combination: Insight from Tumor Immune Microenvironment (TIME) The view of Radiotherapy (RT) as a simple inducer of DNA damage resulting in tumor cell death has dramatically changed in recent years, and it is now widely accepted that RT can trigger an immune response which provides a sound basis for combining RT with immunotherapy. Given that, radiation can be delivered with different regimens, its effect on immune responses and Tumor Immune Microenvironment (TIME) may vary with dose and fractionation schedule. This fractional dose dependency may need to be more considered because of recent developments in RT delivery techniques making it possible to deliver precisely higher dosages per fraction (hypofractionation) while reducing exposure to normal tissues. Although combining radiotherapy with immunotherapy could be a promising strategy for synergistic enhancement of treatment efficacy, the selection of the best-matched combination of immunotherapy with each radiotherapy scheme remains to be addressed. Thus, for designing better therapeutic combinations, it is necessary to understand the immunological effects of RT. Here, we review the impact of conventional and different hypofractionation radiation schedules on the TIME. Subsequently, we highlight how knowing about these interactions may have implications for choosing a rational combination with targeted therapies. Conventional radiotherapy, Hypofractionated radiotherapy, Immunotherapy, Radiotherapy, Tumor immune microenvironment 209 215 https://www.ajmb.org/En/Article.aspx?id=60552 https://www.ajmb.org/PDF/En/FullText/60552.pdf MasoumehAlimohammadi Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran92080HaniyehGhaffari-Nazari Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran92081RezaAlimohammadiDepartment of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran92082MohsenBakhshandehDepartment of Radiology Technology, Allied Medical Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran92083NimaRezaei186Seyed AmirJalali 92084

en Gypenosides Production and Spermatogenesis Recovery Potentials of Extracts from Cell Suspension Cultures of Gynostemma pentaphyllum Background: Gynostemma pentaphyllum (GP), also called Giao-co-lam, is a traditional Vietnamese herb, also known as the "Herb of Immortality", that grows throughout Asian countries and is used for the treatment of hematuria, edema in the pharynx and neck, tumors, and trauma. Methods: In this study, we investigated the effects of culture conditions on cell growth and total gypenoside accumulation in the GP suspension cells. Cells were cultured on Murashige and Skoog (MS) medium supplemented with 2.0 mg/L KIN and 0.5 mg/L IBA, and different inoculum sizes (2-4 g) for 10-24 days. Results: The results showed that the optimum inoculum size and shaking speed were 3 g of callus and 120 rpm, respectively. The highest cell biomass reached was 5.833 g of fresh weight, corresponding to 0.136 g of dry weight after 20 days of culture. The total gypenoside and Rb1 accumulation was the highest after 18 days of culture, with 46.498 mg/g and 0.038 mg/g dry weight, respectively. In addition, the crude extract from GP cell suspension cultures remarkably improved pathological changes in mouse testicular tissue after scrotal heat exposure. Blood testosterone levels were significantly increased in heat-exposed mice treated with the GP cell suspension culture extract. Conclusion: Taken together, these results suggest that GP bio-mass production by cell suspension cultures leads to the accumulation of gypenosides in large amounts, and provides the potential for the recovery of spermatogenesis following heat stress. Gynostemma pentaphyllum, Gypenoside, Heat stress, Saponin Rb1, Spermatogenesis, Suspension cells 216 222 https://www.ajmb.org/En/Article.aspx?id=60553 https://www.ajmb.org/PDF/En/FullText/60553.pdf TungNguyen-Thanh Institute of Biomedicine, University of Medicine and Pharmacy, Hue University, Hue 49000, Vietnam92087SangDang-Ngoc Vo Nguyen Giap Gifted High School, Quang Binh 47000, Vietnam92088DungTran-QuocUniversity of Education, Hue University, Hue 49000, Vietnam92089QuangHoang-Tan92090

en Activity of Citrus aurantium and Lavandula angustifolia in Alzheimer’s Disease Symptoms in Male Wistar Rats Background: Alzheimer's Disease (AD) is one of the most prevalent chronic neurodegenerative disorders. The present study aims to better understand the mechanism by which Citrus aurantium (C. aurantium) and Lavandula angustifolia (L. angustifolia) hydro–alcoholic extracts were used to treat AD and anti–oxidant issues in a laboratory model. Methods: 15 male Wistar rats, weighing 250±20 gr, aged 6–8 weeks, were used. Amyloids in the brain were found and identified using the shuttle box and Congo red test. ELISA testing for norepinephrine and serotonin, Superoxide Dismutase (SOD), Malondialdehyde (MDA), and Real–time PCR for expression of the APP and GLT1 genes were done. Results: The shuttle box test demonstrated that AD produces behavioral harm, since it significantly reduces passive avoidance learning. The Congo red test revealed that the AD models had much more amyloid beta in their brain tissue than the control. Norepinephrine levels were also decreased by using both extracts in test group. Treatment with both extracts led to a substantial rise in SOD activity and fall in MDA concentration. Conclusion: The gene expression data indicated that the relative expression of the APP and GLT1 genes was shown to be lower in the groups treated with both extracts. C. aurantium and L. angustifolia may therefore offer a multi–target treatment strategy for AD, which calls for more research in this area. Amyloid beta-peptides, Antioxidants, Brain, Citrus, Lavandula, Neurodegenerative diseases, Norepinephrine, Rats, Serotonin 223 231 https://www.ajmb.org/En/Article.aspx?id=60554 https://www.ajmb.org/PDF/En/FullText/60554.pdf AmirArasteh92091MortezaKarimpourDepartment of Biology, Rasht branch, Islamic Azad University, Rasht, Iran92096FaezehFallahDepartment of Biology, Islamic Azad University, Central Tehran branch, Tehran, Iran92093SaraKianiDepartment of Biology, Islamic Azad University, Central Tehran branch, Tehran, Iran92094MaedehKakavanDepartment of Medical Microbiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran92095

en Transient Co-Expression of Bioactive Murine Interferon-Gamma and HBsAg in Tobacco and Lettuce Leaves Background: The synchronous expression of antigen and adjuvant proteins in plant hosts presents an intriguing potential for vaccine production and the enhancement of appropriate immune responses. In this study, we examined the expression of bioactive murine interferon-gamma (mIFN-γ) along with HBsAg in tobacco and lettuce leaves aimed to further perform the analysis of immune responses in the mouse model. Methods: Monocistronic and bicistronic cassettes, carrying genes encoding mIFN-γ and HBsAg in various orders, were constructed. These cassettes were placed under the control of the 35S CaMV promoter and included the 5ʹ leader sequence of Tobacco Ech Virus (TEV). Through Agrobacterium infiltration, the cassettes were transferred into plant leaves. The concentration of mIFN-γ in different constructs and HBsAg was tested by ELISA. Murine IFN-γ was characterized through Western blotting, and its bioactivity was evaluated by assessing the up-regulation of MHC class II in macrophages derived from mouse bone marrow. Results: Extracts of agroinfiltrated leaves contained recombinant mIFN-γ and HBsAg proteins at about 14 unit/mg and 50 ng/mg of soluble protein, respectively. Subsequently, mIFN-γ was purified from the plant extract and its ability to up-regulate MHC class II in mouse bone marrow-derived macrophages was confirmed by immunofluorescence. Conclusion: The co-expression of recombinant HBsAg and mIFN-γ using TEV 5ʹ leader-based cassettes in tobacco and lettuce leaves produced both proteins with active mIFN-γ in different concentrations. The attractive utility and feasibility of using plant transient co-expression systems aimed to co-delivery of vaccine antigen and appropriate cytokine to elicit immune response for different applications. Agrobacterium, Cytokines, Hepatitis B surface antigens, Plant proteins 232 238 https://www.ajmb.org/En/Article.aspx?id=60555 https://www.ajmb.org/PDF/En/FullText/60555.pdf SaraMohammadzadehDepartment of Medical Biotechnology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran92097MahshidAmiriLaboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, United States of America92098ParastooEhsani514

en Production of Egg Yolk Antibody (IgY) against Vibrio cholerae O1: Protective Effect in Mice Background: Cholera is an acute intestinal infection caused by Vibrio cholera (V. cholera). The development of antibodies against specific V. cholerae may have a therapeutic effect. In the present research, we investigated the protective effect of egg yolk Immunoglobulin (IgY), which was produced by immunizing hens with formaldehyde-killed V. cholerae O1 and subsequently the isolated IgY was orally administrated to the V. cholerae O1 infected mice for evaluation of its immunizing capability. Methods: In the current study, hens were immunized three times with formaldehyde-killed V. cholerae O1 (1.5× 107 CFU/mL) and an equal volume of adjuvant. The IgY was isolated from egg yolk by polyethylene glycol method. The validity and activity of isolated IgY were confirmed with SDS-PAGE and ELISA methods, respectively. Subsequently IgY was orally administered to suckling mice following challenge with V. cholerae O1. ELISA results showed high antibody titer in the serum and egg yolk. Also, SDS-PAGE analysis showed successful purification of IgY and anti-V. cholerae IgY prevented the death of mice infected with V. cholerae O1. The anti-V. cholera IgY was administered at 2, 4, 6 hours’ intervals after 3 hours of inoculation of mice with V. cholerae O1. Results: Results showed that the rate of surviving mice (2 mg/mL of IgY) were 60% after 4 hours and 40% after 6 hours and the rate of surviving mice (5 mg/mL of IgY) was 70% after 4 hours and 60% after 6 hours. Conclusion: The findings suggested the egg yolk-driven IgY as a natural antibacterial protein, could be effective in the prevention and treatment of cholera disease. Antibodies, Chicken, Immunoglobulin Y, Mice, Vibrio cholerae O1 239 244 https://www.ajmb.org/En/Article.aspx?id=60550 https://www.ajmb.org/PDF/En/FullText/60550.pdf MohammadShoushtariAnatomical Sciences Research Center Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran92073Ali BaratShooshtariKaraj Branch, Islamic Azad University, Karaj, Iran92074SepidehAsadiDepartment of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran92075YousofKaramiFaculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran92076MohsenHonariPayame Noor University, Tehran, Iran92077JavadFathi91902MehdiZeinoddini92079Ghorban AliAlizadehPayame Noor University, Tehran, Iran92078

en Association of Catechol-O-Methyl-Transferase and Estrogen Receptors Polymorphism with Severity of Temporomandibular Disorder in Iranian Patients Background: There are many studies which strongly suggest that the pathophysiology of Temporomandibular joint Disorder (TMD) may also be influenced by genetic conditions. The current study was aimed to evaluate the hypothesis that the polymorphism of estrogen receptor genes, estrogen receptor 1 and 2 (ESR1 and ESR2), and the gene Catechol -O-Methyl-Transferase (COMT) could be Predisposing factor for TMD. Methods: In this case-control study, blood sample were taken from 100 TMD diagnosed patients based on Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and 103 healthy individuals as the control group. Tetra ARMS-PCR method was used to amplify and identify COMT rs4680, ESR1 rs1643821, and ESR2 rs1676303 gene polymorphism. Results: ESR1 genotype AA and GA showed significantly increase probability (OR= 4.80, OR=2.98, respectively) of TMD. ESR2 T/T homozygosity was associated with decreased risk for TMD (OR=0.41). The relationship between COMT and TMD was not statistically significant (p>00.05). The relationship between the severity of TMD and ESR1 was significant (p=0.003). According to the inheritance pattern the COMT and ESR1 gene, in the dominant pattern can be susceptible to TMD and in ESR2 gene, in the recessive pattern can be protective to TMD. Conclusion: It seems that SNPs of ESR1 rs1643821 has a susceptible role and ESR2 rs1676303 has a protective role against TMD. Also, we add evidences that various genotype of COMT rs4680 were not statistically different between case and control, but allele A in the dominant inherence pattern can be susceptible to TMD. Alleles, Estrogen receptor alpha, Estrogen receptor beta, Human, Inheritance patterns, Polymorphism 245 252 https://www.ajmb.org/En/Article.aspx?id=60556 https://www.ajmb.org/PDF/En/FullText/60556.pdf HassanRoudgariDepartment of Applied Medicine, School of Medicine, Polwarth Building, Foresterhill Health Campus, Aberdeen University, Aberdeen, UK92099ShamsolmouloukNajafiDepartment of Oral Medicine, Dental Research Center, School of Dentistry, Tehran University of Medical Science, Tehran, Iran1053SheydaKhalilian Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran92100ZahraGhafarzadehSchool of Dentistry, Tehran University of Medical Science, Tehran, Iran92101AidaHahakzadehSchool of Dentistry, Tehran University of Medical Science, Tehran, Iran92102SheidaBehazinSchool of Dentistry, Tehran University of Medical Science, Tehran, Iran92103NafisehSheykhbahaei92104

en Association between PON1-rs662 Gene Polymorphism and Diabetic Retinopathy in Population of the Qom, Iran Background: Diabetic retinopathy is the most severe diabetic microvascular complication that causes changes in the vessel wall. One of the genes involved in this disease is PON1, which encodes paraoxanase1 protein in liver and kidney. It might regulate inflammatory and microvascular responses to the disease. The rs662 T>C is one of the single nucleotide polymorphisms of this gene that changes glutamine to arginine at position 192. Methods: In this study, 300 samples were collected, including 100 healthy and 100 diabetics without retinopathy, and 100 diabetics retinopathies were studied and their age range was from 30 to 80 years. Then 2.5 ml of blood was collected from all relevant individuals in tubes containing EDTANa2. This polymorphism was examined by tetra-ARMS PCR. Results: Results showed that there is no significant correlation between genotypes and alleles related to PON1 and Diabetes (CC genotype: p=0.609; C allele: p=0.228). On the other hand, an association was observed between PON1 and diabetic retinopathy (CT+CC genotype: p<0.001; CT allele: p<0.001). Considering that the Polyphen database examined the changes caused by replacing the amino acid arginine instead of glutamine at position 129 on the protein, it does not consider these changes dangerous and has introduced this polymorphism as benign. Conclusion: Based on the findings of this study, the rs662 locus could be considered as one of the molecular markers in future research. Diabetic angiopathies, Diabetic retinopathy, Polymerase chain reaction , Polymorphism, PON1 253 257 https://www.ajmb.org/En/Article.aspx?id=60557 https://www.ajmb.org/PDF/En/FullText/60557.pdf FatemeSabbaghian BidgoliDepartment of Molecular and Cell Biology, Faculty of Sciences, University of Mazandaran, Babolsar, Iran92105AbasaltHosseinzadeh ColagarDepartment of Molecular and Cell Biology, Faculty of Sciences, University of Mazandaran, Babolsar, Iran92106RoohollahNakhaei Sistani92108MajidTafrihi92107

en Evaluation of Seroconversion Rate Following SARS COV 2 Vaccination in Health Care Workers at Shahid Beheshti University of Medical Sciences Background: Vaccines are the most effective way to prevent Coronavirus 2 severe acute respiratory syndrome (SARS-CoV-2). This study examines and compares the efficiency of AstraZeneca, Sinopharm, and Sputnik vaccines and the correlation of antibody response with age, sex, and history of corona disease in employees of Shahid Beheshti University of Medical Sciences. Methods: 202 participants were included, of which 82 were administered the AstraZeneca, 59 were given the Sinopharm, and 61 were given the Sputnik vaccine. SARS-CoV-2 IgM and IgG antibody levels were checked four weeks after passing the second dose of all three vaccines using the enzyme-linked immunosorbent assay (ELISA) technique. Results: There was no significant difference between the amount of IgM and IgG antibodies among three vaccines (p=0.056). For all three vaccines, gender and age did not significantly affect the amount of IgM and IgG antibodies. The history of infection with COVID-19 increased the antibody response (p>0.5). Conclusion: The titer of IgM and IgG antibodies were not statistically significantly different. The IgM and IgG antibodies produced by vector-based vaccines are higher than the Sinopharm vaccine. Gender did not affect the produced antibody titer. No significant linear relationship was found between age and antibody titer. In people from this study who received two doses of the AstraZeneca vaccine and had a corona history, the average amount of both IgM and IgG antibodies was measured more than the other participants. Antibodies, COVID19 vaccines, SARS-CoV-2 258 263 https://www.ajmb.org/En/Article.aspx?id=60558 https://www.ajmb.org/PDF/En/FullText/60558.pdf MasoudAlaviDentist, Private Practice, Tehran, Iran92109MohammadMousaviDentofacial Deformities Research Center, Research Institute of Dental Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran92110MohammadJazayeriDepartment of Virology, School of Public Health Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran92111AsgharEbadifar891