Original Article (Clinical Toxicology)


Investigation of NSD2 Protein Expression Changes in Hepatocellular Carcinoma Cells After Treatment With Curcumin and Phthalates

Seyed Ehsan Alavian, Masoud Salehipour, Saeed Zaker Bostanabad, Farzaneh Tafvizi, Mohammad Heiat

International Journal of Medical Toxicology and Forensic Medicine, Vol. 13 No. 3 (2023), 17 October 2023,
https://doi.org/10.32598/ijmtfm.v13i3.42344

Background: Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide. The role of molecular markers in the development and progression of this cancer has been extensively studied. The overexpression of the 90-kilobase protein methyltransferase NSD2 (nuclear receptor binding SET domain- protein 2) is associated with tumor development and some types of cancers. This study aims to investigate the changes in NSD2 protein expression in HCC cells after treatment with curcumin and phthalates.
Method: This study compared the NSD2 protein expression in HepG2 cancer cells and fibroblast cells that were either untreated or treated with the half-maximal inhibitory concentration (IC50%) of phthalates, curcumin, or their combination. The Western blot method and protein quantification were used to detect and determine NSD2 protein levels, and ImageJ software was used to analyze the desired bands.
Results: Curcumin, phthalates, and their combination reduced the expression of NSD2 in HepG2 cancer cells and normal fibroblast cells compared to untreated cells (P<0.001). This decrease in expression was more significant in cells treated with both curcumin and phthalates than in treatment with curcumin or phthalates alone.
Conclusion: The IC50% of curcumin, phthalates, and their combination can reduce NSD2 expression, where the effect of the combined form is greater. Therefore, the combination of phthalates and curcumin is recommended as a potential anti-cancer agent against HCC cells with an effect on reducing NSD2 expression.

Investigating Bisphenol A Level Estimation and Possible Effects on Fetal Biometry

Reham Nafad Elbendary, Abla Abdel Meguid Attia, Mohamed Ahmed Yehia Zakaria, Sakr Mohammed Sakr, Hisham Mamdouh Hamed Haggag, Sara Hamed N. Taha, Howaida Saeed Mohammed

International Journal of Medical Toxicology and Forensic Medicine, Vol. 13 No. 3 (2023), 17 October 2023, Page 42805
https://doi.org/10.32598/ijmtfm.v13i3.42805

Background: The estrogenic endocrine disruptor bisphenol A (BPA), which is used in plastics and resins, may have an impact on the fetus’s growth and development and can modify postnatal development. This study aims to assess how bisphenol A affects fetal biometry.
Methods: This analytical cross-sectional study included 384 healthy Egyptian women in their third trimester during childbearing (15–44 years). They were selected from the outpatient Clinic of Obstetrics and Gynecology at Kasr El-Ainy Hospital, Cairo, Egypt. Fetal biometry was measured and urine samples were collected to estimate BPA levels.
Results: Fetal weight, centile, and corrected bisphenol A levels were significantly higher in the studied age groups (P<0.05). A significant positive correlation was found between BPA level and estimated fetal weight, centile, and age of the mother per year. On the other hand, no significant difference was detected with other fetal measurements in the studied groups (P>0.05).
Conclusion: Fetal exposure to BPA is associated with higher estimated fetal weight and centile commonly in the maternal age range 25 to 35 years.

Original Article (General Medicine)


Factors Affecting the Serum Cotinine Level of Male Smokers in Malang, Indonesia

Kumboyono Kumboyono, Indah Nur Chomsy, Wahyu Santoso Hidayat, Ardhi Khoirul Hakim, Nadya Neyza Shalshabilla, Hidayat Sujuti, Cholid Tri Tjahtjono, Arie Srihardyastutie, Tita Hariyanti, Titin Andri Wihastuti

International Journal of Medical Toxicology and Forensic Medicine, Vol. 13 No. 3 (2023), 17 October 2023, Page 40130
https://doi.org/10.32598/ijmtfm.v13i3.40130

Background: In tobacco, nicotine is the primary toxic agent that causes health problems. As a primary metabolite of nicotine, cotinine is frequently used as an accurate measure of exposure to tobacco smoke. This study aims to find the factors affecting the serum cotinine level of male smokers in Malang, Indonesia.
Methods: This cross-sectional study was conducted on 183 men who smoke regularly in Malang, Indonesia. They were selected by a purposive sampling method. Nicotine dependency and cotinine level were measured using the Fagerstrom test for nicotine dependence and the human cotinine ELISA Kit, respectively. Multiple linear regression analysis was performed to determine the effect of age, smoking duration, cigarette type, and the nicotine dependence on the continue level. ANOVA and independent t-test were also used for testing the study hypothesis. The significance level was set at 0.05.
Results: Based on the ANOVA results, the factors of age, smoking duration, type of cigarette, and nicotine dependence together had a significant effect on the cotinine level (P<0.001). Based on the independent t-test results, only the age factor had a significant effect on the cotinine level (P<0.001).
Conclusion: Older male smokers may have higher cotinine level. Other factors including duration of smoking, type of cigarette, and nicotine dependence have no significant effect on cotinine level of male smokers.

Side Effects of COVID-19 Vaccination Among Healthcare Workers in Tehran, Iran

Davood Yadegarynia, Shabnam Tehrani, Fahimeh Hadavand, Shahnam Arshi, Zahra Abtahian, Amirreza Keyvanfar, Azar Darvishi, Afshin Zarghi

International Journal of Medical Toxicology and Forensic Medicine, Vol. 13 No. 3 (2023), 17 October 2023,
https://doi.org/10.32598/ijmtfm.v13i3.40536

Background: Since the emergence of coronavirus disease 2019 (COVID-19), many people have been vaccinated worldwide. Despite the preventive role of vaccines, their side effects face disease management with challenges. This study aims to investigate the side effects of COVID-19 vaccination among healthcare workers in Tehran, Iran.
Methods: This cross-sectional study was conducted from April to October 2022 on 377 healthcare workers in Tehran, Iran. Data collection was carried out through an interview by a researcher using a checklist assessing systemic and local side effects of COVID-19 vaccines.
Results: The mean age of participants was 36.03±10.24 years, and 68.2% were female. Participants experienced significantly more local (26.5% vs. 14.3%, P<0.001) and systemic (52.0% vs. 31.8%, P<0.001) side effects after the first dose than after the second dose. After the first dose, AstraZeneca (45.9%) caused significantly more local reactions than Sputnik V (21.7%) and Sinopharm (14.5%). AstraZeneca (83.7%) caused significantly more systemic side effects than Sputnik V (50.7%) and Sinopharm (14.5%). The prevalence of local and systemic side effects after the first dose was significantly different in terms of vaccine types (P<0.001). After the second dose, AstraZeneca (20.4%) caused significantly more local reactions than Sputnik V (12.8%) and Sinopharm (10.5%) (P<0.001). Additionally, AstraZeneca (38.8%) and Sputnik V (37.4%) caused significantly more systemic side effects than Sinopharm (7.9%) (P<0.001).
Conclusion: Most healthcare workers in Tehran experienced flu-like symptoms and local reactions at the injection site after vaccination against COVID-19, mainly after the first dose. They had more side effects after vaccination with AstraZeneca and Sputnik V, compared to Sinopharm.

Serum Klotho Level and its Related Factors Among Male Opioids Addicts With Normal Renal Function Compared to Healthy Male Non-smokers and Smokers in Tabriz, Iran

Maryam Zaare Nahandi, Rasoul Estakhri, Saiedeh Razi Soofiyani, Ali Ostadi, Hosein Azizi, Ahad Banagozar Mohammadi, Masoomeh Kashef Nejad, Ali Banagozar Mohammadi, Elghar Soltani

International Journal of Medical Toxicology and Forensic Medicine, Vol. 13 No. 3 (2023), 17 October 2023,
https://doi.org/10.32598/ijmtfm.v13i3.42587

Background: Klotho is an aging-suppressor gene that encodes a single-pass transmembrane protein and acts as a hormone. In this study, we aim to investigate the serum α-Klotho level in male opioids addicts with normal kidney function compared to healthy male non-smokers and smokers in Tabriz, Iran.
Methods: Participnts were 87 men with normal kidney function referred to Sina Educational Research and Treatment Center in Tabriz, Iran (29 opioids addicts, 29 healthy non-smokers, and 29 healthy smokers). Blood samples were collected to measure the soluble a-Klotho level using an ELISA kit. Furthermore, blood creatinine (Cr) and hemoglobin (Hb) levels was measured. Body mass index (BMI) was also calculated for all participants.
Results: In addicts, BMI, Hb, and Cr levels were significantly lower than in healthy non-smokers and smokers, but their Klotho level was higher (P>0.05). The Klotho level in healthy smokers was significantly lower than in healthy non-smokers and addicts. The Klotho level of healthy smokers decreased as the pack year increased, but the duration of opioid addiction had no significant association with the Klotho level. There was no significant difference in the Klotho level between control groups (non-smokers and smokers) and men with addiction to different types of opioids.
Conclusion: The Klotho level in male opioid addicts is significantly higher than in smokers. There is a significant negative correlation between BMI and Klotho levels among men with normal BMI and overweight. Further studies are recommended in these fields.

Case Report


The Sudden Death of a Pregnant Woman With Takotsubo Cardiomyopathy Following a Legal Abortion: A Case Report

Seyed Ali Mohtarami, Ali Naghsh, Aria Hedjazi

International Journal of Medical Toxicology and Forensic Medicine, Vol. 13 No. 3 (2023), 17 October 2023, Page 42616
https://doi.org/10.32598/ijmtfm.v13i3.42616

Background: Takotsubo cardiomyopathy (TCM) is characterized by left ventricular dysfunction and apical ballooning due to physical or mental stress in the absence of coronary artery disease. This transient heart disorder is rare in pregnancy. It may affect women of reproductive age.
Case Presentation: The case was a 38-year-old woman in the first trimester of pregnancy with a history of TCM diagnosis one year ago, admitted to the hospital for a legal abortion. At the time of hospitalization, echo cardiography, echo cardiography, and clinical tests results were normal; however, due to stressful factors, such as the cancellation of the dilation & curettage (D&C) procedure, despite being transferred to the operating room (due to the absence of a gynecologist), receiving misoprostol for two consecutive days, the prolongation of surgery time, as well as the absence of a psychiatrist to reduce stress during the operation, suffered from recurrent TCM and eventually expired. In the autopsy, the cause of death was a massive pulmonary embolism.
Conclusion: In pregnant women, there is a possibility of TCM recurrence due to changes in hormonal levels and emotional and physical stress caused by pregnancy. Therefore, when performing a surgical procedure such as D&C, a team consisting of gynecologists, cardiologists, and psychiatrists should be present to avoid dangerous complications such as sudden death.

Postmortem Toxicology of Tadalafil in a Forensic Case

Maria Laura Schirripa, Letizia Gnetti, Edda Emanuela Guareschi

International Journal of Medical Toxicology and Forensic Medicine, Vol. 13 No. 3 (2023), 17 October 2023, Page 40058
https://doi.org/10.32598/ijmtfm.v13i3.40058

Tadalafil is an inhibitor of the human enzyme cyclic guanosine monophosphate–specific phosphodiesterase, type 5 (PDE-5). As a mild vasodilator, it is primarily used for the treatment of erectile dysfunction, an increasingly common condition in men. It is also used for treatment of benign prostatic hyperplasia and pulmonary arterial hypertension. Adverse events of this drug are rare. Absolute contraindications include serious cardiac disease. Despite the widespread use of tadalafil, very little is known about its toxicology in forensic pathology and its association with post-mortem redistribution. This study presents a forensic case with possible contribution of tadalafil. The administration of tadalafil might act as a concurrent cause or contributing factor for lethal cardiogenic shock in people with cardiac disease.

Delayed Death Due to Methanol Poisoning: An Autopsy Case Report

Razuin Rahimi, Norizal Mohd Noor, Khairul Adli B Nikman, Noor Alicezah Bt Mohd Kasim

International Journal of Medical Toxicology and Forensic Medicine, Vol. 13 No. 3 (2023), 17 October 2023,
https://doi.org/10.32598/ijmtfm.v13i3.42170

Methanol is a non-drinking type of alcohol used for industrial and automotive purposes. Methanol itself is not dangerous, but its harmful metabolites may cause the accumulation of acid in the blood, leading to metabolic acidosis, permanent blindness, and death. In this case report study, the case was a 28-year-old Nepalese man who was admitted in a semi-unconscious state to the emergency department. A working diagnosis of methanol poisoning was made. After more than two weeks, he succumbed to death due to a worsening cerebral infarction. At autopsy, extensive hemorrhagic infarction was observed, involving bilateral cerebral hemispheres. Well-defined subcortical hemorrhages leading to laminar necrosis were seen at the frontoparietal lobes. Cystic or lacunar necrosis was present at the basal ganglia. The brainstem showed the presence of duret hemorrhage. The man died approximately three weeks after the methanol ingestion. This case highlights the important pathological changes and accumulating effects of methanol in the brain.