Publications by authors named "Farshad Shirazi"

71 Publications

Microfluidic platform for synthesis and optimization of chitosan-coated magnetic nanoparticles in cisplatin delivery.

Carbohydr Polym 2021 Aug 7;265:118027. Epub 2021 Apr 7.

Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran.

In this study, magnetic core/chitosan shell Nanoparticles (NPs) containing cisplatin were synthesized via cisplatin complexation with tripolyphosphate as the chitosan crosslinker using two different procedures: a conventional batch flow method and a microfluidic approach. An integrated microfluidic device composed of three stages was developed to provide precise and highly controllable mixing. The comparison of the results revealed that NPs synthesized in microchannels were monodisperse 104 ± 14.59 nm (n = 3) in size with optimal morphological characteristics, whereas polydisperse 423 ± 53.33 nm (n = 3) nanoparticles were obtained by the conventional method. Furthermore, cisplatin was loaded in NPs without becoming inactivated, and the microfluidic technique demonstrated higher encapsulation efficiency, controlled release, and consequently lower IC50 values during exposure to the A2780 cell line proving that microfluidic synthesized NPs were able to enter the cells and release the drug more efficiently. The developed microfluidic platform presents valuable features that could potentially provide the clinical translation of NPs in drug delivery.
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http://dx.doi.org/10.1016/j.carbpol.2021.118027DOI Listing
August 2021

Death by hand sanitizer: syndemic methanol poisoning in the age of COVID-19.

Clin Toxicol (Phila) 2021 Mar 23:1-6. Epub 2021 Mar 23.

Arizona Poison and Drug Information Center, University of Arizona College of Pharmacy, Tucson, AZ, USA.

Background: The advent of COVID-19 increased attention to hand hygiene in prevention of disease transmission. To meet the increased demand for hand sanitizer during the pandemic, the US FDA issued an Emergency Use Authorization allowing new manufacturers and importers to enter the market. Some of the newly introduced hand sanitizer products contained methanol in lieu of ethanol or isopropanol. We describe five patients with fatal methanol poisoning resulting from hand sanitizers improperly containing methanol.

Case Summary: Comparing a 5-month period from 2019 to the same time frame in 2020, the Arizona Poison and Drug Information Center has seen an increase of 124% in exposures to hand sanitizer. Of these cases, 28% involved methanol-contaminated hand sanitizer. Five of these patients died from methanol poisoning. All five cases had similar clinical features with severe high anion gap metabolic acidosis and, in four patients, elevated osmolal gap. Methanol concentrations were consistently very elevated, but these results were not available before the patients succumbed. Four of the patients received fomepizole and adjunctive care. Two patients received emergency extracorporeal therapy. All five died despite maximal treatment efforts.

Conclusion: During the pandemic in 2020, there was a proliferation of alcohol-based hand sanitizers which contained methanol. Exposure to these products, which failed to meet regulatory standards, led to increased harm and death. Challenges to treatment of methanol poisoning, especially in rural areas, include lack of access to timely laboratory measurement of methanol concentrations and lack of available emergency hemodialysis without transfer of the patient.
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http://dx.doi.org/10.1080/15563650.2021.1895202DOI Listing
March 2021

A double-edged sword of using opioids and COVID-19: a toxicological view.

Subst Abuse Treat Prev Policy 2020 12 3;15(1):91. Epub 2020 Dec 3.

Medical Toxicology and Drug Abuse Research Center, Birjand University of Medical Sciences, Birjand, Iran.

Today, COVID-19 is spreading around the world. Information about its mechanism, prognostic factors, and management is minimal. COVID-19, as a human disease, has several identifying phases. Physicians of patients with COVID-19 may be interested in knowing whether opioid use disorder may affect their patients' course or prognosis. This information may be crucial when considering the opioid epidemic in the US and other parts of the world. Opioid use at high doses and over several months duration can mitigate the immune system's function, which may complicate the course of COVID-19 disease. Potential suppression of parts of the immune response may be important in prevention, clinical support, and therapeutic use of medications in various phases of the COVID-19. Specifically, opioid use disorders via an inhalation route may enhance the "late hyper-inflammatory phase" or result in end-organ damage. It is well established that opioids decrease ventilation as their effect on the medullary respiratory centers increases the risk of pneumonia. This increased risk has been associated with immune-suppressive opioids. The ultimate role of opioids in COVID-19 is not clear. This paper endorses the need for clinical studies to decipher the role and impact of chronic opioid use on viral diseases such as COVID-19.
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http://dx.doi.org/10.1186/s13011-020-00333-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711252PMC
December 2020

Cardiovascular Effects of Medical Marijuana: A Systematic Review.

Am J Med 2021 02 11;134(2):182-193. Epub 2020 Nov 11.

Cardiology Section, John D. Dingell VA Medical Center, Detroit, Mich. Electronic address:

Utilization of marijuana as a medicinal agent is becoming increasingly popular, and so far, 25 states have legalized it for medical purposes. However, there is emerging evidence that marijuana use can result in cardiovascular side effects, such as rhythm abnormalities, syncope/dizziness, and myocardial infarction, among others. Further, there are currently no stringent national standards or approval processes, like Food and Drug Administration (FDA) evaluation, in place to assess medical marijuana products. This review includes the largest up-to-date pooled population of patients with exposure to marijuana and reported cardiovascular effects. Although purported as benign by many seeking to advance the use of marijuana as an adjunctive medical therapy across the country, marijuana is associated with its own set of cardiovascular risks and deserves further definitive study and the same level of scrutiny we apply in research of all other types of medications. When used as a medicinal agent, marijuana should be regarded accordingly, and both clinical providers and patients must be aware of potential adverse effects associated with its use for early recognition and management.
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http://dx.doi.org/10.1016/j.amjmed.2020.09.015DOI Listing
February 2021

Can dantrolene be used in the treatment of cardioglycosides poisonings?

Expert Opin Drug Metab Toxicol 2021 Jan 10;17(1):1-2. Epub 2020 Nov 10.

Arizona Poison & Drug Information Center, the University of Arizona, college of pharmacy and university of Arizona, college of medicine , Tucson, Arizona, USA.

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http://dx.doi.org/10.1080/17425255.2021.1843632DOI Listing
January 2021

The Photothermal Effect of Targeted Methotrexate-Functionalized Multi-Walled Carbon Nanotubes on MCF7 Cells.

Iran J Pharm Res 2019 ;18(Suppl1):221-236

Department of Toxicology and Pharmacology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Our goal is to reduce the release rate of methotrexate (MTX) and increase cell death efficiency.Carboxylated multi-walled carbon nanotubes (MWCNT-COOH) were functionalized with MTX as a cytotoxic agent, FA as a targeting moiety and polyethylene amine (PEI) as a hydrophilic agent. Ultimately, MWCNT-MTX and MWCNT-MTX-PEI-FA were synthesized. Methotrexate release studies were conducted in PBS and cytotoxic studies were carried out by means of the MTT tassay. Methotrexate release studies from these two carriers demonstrated that the attachment of PEI-FA onto MWCNT-MTX reduces the release rate of methotrexate. The IC50 of MWCNT-MTX-PEI-FA and MWCNT-MTX have been calculated as follows: 9.89 ± 0.38 and 16.98 ± 1.07 µg/mL, respectively. Cytotoxic studies on MWCNT-MTX-PEI-FA and MWCNT-MTX in the presence of an IR laser showed that at high concentrations, they had similar toxicities due to the MWCNT's photothermal effect. Targeting effect studies in the presence of the IR laser on the cancer cells have shown that MWCNT-MTX-PEI-FA, MWCNT-MTX, and f-MWCNT have triggered the death of cancer cells by 55.11 ± 1.97%, 49.64 ± 2.44%, and 37 ± 0.70%, respectively. The release profile of MTX in MWCNT-MTX-PEI-FA showed that the presence of PEI acts as a barrier against release and reduces the MTX release rate. In the absence of a laser, MWCNT-MTX-PEI-FA exhibits the highest degree of cytotoxicity. In the presence of a laser, the cytotoxicity of MWCNT-MTX and MWCNT-MTX-PEI-FA has no significant difference. Targeting studies have shown that MWCNT-MTX-PEI-FA can be absorbed by cancer cells exclusively.
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http://dx.doi.org/10.22037/ijpr.2020.14484.12423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393047PMC
January 2019

Identification and Quantification of Texture Soy Protein in A Mixture with Beef Meat Using ATR-FTIR Spectroscopy in Combination with Chemometric Methods.

Iran J Pharm Res 2019 ;18(Suppl1):190-197

Department of Toxicology and Pharmacology, School of Pharmacy, Shahid Beheshti University of Medical Science, Tehran, Iran.

Meat, as an important source of protein, is one of the main parts of many people's diet. Due to economic interests and thereupon adulteration, there are special concerns on its accurate labeling. In this study Fourier transform infrared (ATR-FTIR) spectroscopy combined with chemometric techniques (principal component analysis (PCA), artificial neural networks (ANNs), and partial least square regression (PLS-R)) were employed for discrimination of pure beef meat from textured soy protein plus detection and quantification of texture soy protein in a mixture with beef meat. Spectral preprocessing was carried out on each spectra including Savitzki-Golay (SG) smoothing filter, Standard Normal Vitiate (SNV), scatter correction (MSC), and min-max normalization. Spectral range 1700-1071 cm was selected for further analysis. Principal component analysis showed discrete clustering of pure samples. In the next step, supervised artificial neural networks (ANNs) were performed for classification and discrimination. The results showed classification accuracy of 100% using this model. Furthermore, PLS-R model correlated the actual and FTIR estimated values of texture soy protein in beef meat mixture with coefficient of determination (R) of 0.976. In conclusion, it was demonstrated that ATR-FTIR spectroscopy along with PCA and ANNs analysis might potentially replace traditional laborious and time-consuming analytical techniques to detect adulteration in beef meat as a rapid, low cost, and highly accurate method.
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http://dx.doi.org/10.22037/ijpr.2019.111580.13242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393053PMC
January 2019

Serious Adverse Health Events, Including Death, Associated with Ingesting Alcohol-Based Hand Sanitizers Containing Methanol - Arizona and New Mexico, May-June 2020.

MMWR Morb Mortal Wkly Rep 2020 Aug 14;69(32):1070-1073. Epub 2020 Aug 14.

Alcohol-based hand sanitizer is a liquid, gel, or foam that contains ethanol or isopropanol used to disinfect hands. Hand hygiene is an important component of the U.S. response to the emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). If soap and water are not readily available, CDC recommends the use of alcohol-based hand sanitizer products that contain at least 60% ethyl alcohol (ethanol) or 70% isopropyl alcohol (isopropanol) in community settings (1); in health care settings, CDC recommendations specify that alcohol-based hand sanitizer products should contain 60%-95% alcohol (≥60% ethanol or ≥70% isopropanol) (2). According to the Food and Drug Administration (FDA), which regulates alcohol-based hand sanitizers as an over-the-counter drug, methanol (methyl alcohol) is not an acceptable ingredient. Cases of ethanol toxicity following ingestion of alcohol-based hand sanitizer products have been reported in persons with alcohol use disorder (3,4). On June 30, 2020, CDC received notification from public health partners in Arizona and New Mexico of cases of methanol poisoning associated with ingestion of alcohol-based hand sanitizers. The case reports followed an FDA consumer alert issued on June 19, 2020, warning about specific hand sanitizers that contain methanol. Whereas early clinical effects of methanol and ethanol poisoning are similar (e.g., headache, blurred vision, nausea, vomiting, abdominal pain, loss of coordination, and decreased level of consciousness), persons with methanol poisoning might develop severe anion-gap metabolic acidosis, seizures, and blindness. If left untreated methanol poisoning can be fatal (5). Survivors of methanol poisoning might have permanent visual impairment, including complete vision loss; data suggest that vision loss results from the direct toxic effect of formate, a toxic anion metabolite of methanol, on the optic nerve (6). CDC and state partners established a case definition of alcohol-based hand sanitizer-associated methanol poisoning and reviewed 62 poison center call records from May 1 through June 30, 2020, to characterize reported cases. Medical records were reviewed to abstract details missing from poison center call records. During this period, 15 adult patients met the case definition, including persons who were American Indian/Alaska Native (AI/AN). All had ingested an alcohol-based hand sanitizer and were subsequently admitted to a hospital. Four patients died and three were discharged with vision impairment. Persons should never ingest alcohol-based hand sanitizer, avoid use of specific imported products found to contain methanol, and continue to monitor FDA guidance (7). Clinicians should maintain a high index of suspicion for methanol poisoning when evaluating adult or pediatric patients with reported swallowing of an alcohol-based hand sanitizer product or with symptoms, signs, and laboratory findings (e.g., elevated anion-gap metabolic acidosis) compatible with methanol poisoning. Treatment of methanol poisoning includes supportive care, correction of acidosis, administration of an alcohol dehydrogenase inhibitor (e.g., fomepizole), and frequently, hemodialysis.
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http://dx.doi.org/10.15585/mmwr.mm6932e1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440116PMC
August 2020

Effect of angiotensin II blockers on the prognosis of COVID-19: a toxicological view.

Eur J Clin Microbiol Infect Dis 2020 Oct 16;39(10):2001-2002. Epub 2020 Jun 16.

Denver Health/Rocky Mountain Poison and Drug Safety, Denver, CO, USA.

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http://dx.doi.org/10.1007/s10096-020-03932-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298695PMC
October 2020

Correction to: Toxicity of multi-wall carbon nanotubes inhalation on the brain of rats.

Environ Sci Pollut Res Int 2020 08;27(23):29699

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, P.O. Box: 14155-6153, Tehran, Iran.

This research was financially supported by National Institute for Medical Research Development (NIMAD).
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http://dx.doi.org/10.1007/s11356-020-09667-3DOI Listing
August 2020

Fatal abrin poisoning by injection.

Clin Toxicol (Phila) 2021 Feb 1;59(2):169-171. Epub 2020 Jun 1.

Arizona Poison and Drug Information Center, University of Arizona Arizona Health Sciences Center, Tucson, AZ, USA.

Abrin is a toxin of public health concern due to its lethality, lack of antidote, and potential for use as a bioterrorism agent. Possible routes of exposure include ingestion, inhalation, and injection. Onset of symptoms is often delayed, even in severe cases. In fatal cases, death occurs from multi-organ failure. We describe the clinical course, laboratory, and pathologic findings in a case of fatal human poisoning associated with abrin injection. The seeds in this case were obtained the internet. The Centers for Disease Control and Prevention's Laboratory Response Network detected abrine in the urine confirming abrin exposure in this fatal poisoning.
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http://dx.doi.org/10.1080/15563650.2020.1771360DOI Listing
February 2021

The effect of tramadol on blood glucose concentrations: a systematic review.

Expert Rev Clin Pharmacol 2020 May 12;13(5):531-543. Epub 2020 May 12.

Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences (BUMS) , Birjand, Iran.

Introduction: Studies comprehensively summarizing the impact of tramadol use on glucose homeostasis are very sparse. Thus, the present study was performed to collect and summarize the latest information about this issue in a systematic way.

Areas Covered: An exhaustive literature search was carried out using relevant keywords. Web of Sciences, PubMed, Scopus, and Google scholar were interrogated until 30 June 2019. Case-control, cohort, cross-sectional, clinical trial, case report, and animal studies that focused on the objective of the study were retrieved. This review summarizes the results of 761 papers on glycemic changes due to tramadol exposure. Thirty-six publications reported hypoglycemia and 17 hyperglycemia during tramadol use. Twenty-two studies either reported normal blood glucose concentrations, or did not observe any difference in the blood glucose levels following tramadol use. Finally, hypoglycemia was reported in diabetic individuals exposed to tramadol in 12 studies.

Expert Opinion: The data suggest that primarily hypoglycemia but some degree of hyperglycemia has been reported with tramadol use. Importantly, all studies on tramadol use in diabetes reported hypoglycemia. Tramadol-induced hypoglycemia may be severe in some cases. The risk of alterations in glucose homeostasis accompanying tramadol exposure indicates time importance of careful blood glucose monitoring during tramadol use.
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http://dx.doi.org/10.1080/17512433.2020.1756773DOI Listing
May 2020

Comparison of Vitamin B12, Vitamin D, and Folic Acid Blood Levels in Plumbism Patients and Controls in Eastern Iran.

Biol Trace Elem Res 2021 Jan 21;199(1):9-17. Epub 2020 Mar 21.

Wake Forest School of Medicine Addiction Medicine Program, Winston-Salem, NC, USA.

The aim of this study was to evaluate the blood levels of folic acid, vitamin B12, and 25-hydroxyvitamin D (25-OHD) in patients with lead poisoning compared with control subjects in Eastern Iran. This analytical case-control study was conducted on 40 lead-poisoned patients who were referred to Imam Reza Hospital in Birjand from 2018 to 2019. Blood samples were collected from an additional 40 individuals without lead poisoning as a control group. The results indicated that the mean vitamin B12, vitamin D, and folic acid levels for the case group were 356.5 ± 200.1 pg/ml, 24.38 ± 9.5 ng/ml, and 7.4 ± 3.7 ng/ml, respectively. Mean folic acid level in the case group was significantly lower than control group (7.4 ng/ml vs. 12.70 pg/ml, P = 0.001), whereas the mean of the vitamin D levels at the case group was significantly higher than that of the control group (24.3 ng/ml vs. 20.1 ng/ml, P = 0.03). Moreover, mean vitamin B12 levels were significantly lower in the case group in comparison with the control group (356.5 pg/ml vs. 500.8 pg/ml) (P < 0.001). In the control group, 3 patients had folic acid below normal level (< 6 ng/mL) while 12 cases had folic acid below normal (P < 0.05). Also, none of the control group had low vitamin B12 concentrations (< 180 pg/ml), while 7 cases had vitamin b12 below normal (P < 0.05). Our results suggest that lead may induce folate and vitamin B12 dysregulation. Although we found that vitamin D levels were insufficient in both case and control groups, they were significantly higher in the case group. The interpretation of this result is unclear given inconsistent literature reports on this relationship.
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http://dx.doi.org/10.1007/s12011-020-02119-6DOI Listing
January 2021

Construction of a Mammalian IRES-based Expression Vector to Amplify a Bispecific Antibody; Blinatumomab.

Iran J Pharm Res 2019 ;18(4):2117-2123

Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Blinatumomab, the bispecific T cell engager antibody (BsAb), has been demonstrated as the most successful BsAb to date. Throughout the past decade, vector design has great importance for the expression of monoclonal antibody in Chinese hamster ovary (CHO) cells. It has been indicated that expression vectors based on the elongation factor-1 alpha (EF-1 alpha) gene and DHFR selection marker can be highly effective to produce populations of stably transfected cells in the selection medium. Moreover, the phiC31 integrase system is considered as an attractive and safe protein expression system in mammalian cells and it could integrate a donor plasmid of any size, as a single copy, in to the host genome with no cofactors. In this study, phiC31 integrase technology in combination with DHFR amplification system was used to have an expression vector for future expression of blinatumomab in CHO cells. The gene of interest (BsAb gene) could be joined to DHFR selection marker with the insertion of an internal ribosome entry site (IRES). By positioning the DHFR downstream of BsAb gene and IRES, the transcription of the selection marker can depend on the successful transcription of the BsAb gene, which was located upstream in the expression construct. In this study, FC550A-1 vector was used as the backbone and DHFR selection marker was successfully combined with phiC31 integrase technology to generate a high-expressing construct for BsAb expression in CHO-DG44 cells in future studies.
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http://dx.doi.org/10.22037/ijpr.2019.14387.12351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059065PMC
January 2019

Comparison of transmission FTIR and ATR spectra for discrimination between beef and chicken meat and quantification of chicken in beef meat mixture using ATR-FTIR combined with chemometrics.

J Food Sci Technol 2020 Apr 28;57(4):1430-1438. Epub 2019 Nov 28.

1Department of Toxicology and Pharmacology, School of Pharmacy, Shahid Beheshti University of Medical Science, Tehran, Iran.

Detecting meat adulteration for quality control and accurate labeling is important and needs convenient analytical methods. This study aimed to investigate and compare the application of the transmission and ATR approaches of FTIR followed by principal component analysis (PCA) to not only discriminate between chicken and beef meat but also quantizing chicken portion of mixtures. Two different approaches are presented; spectra preprocessing with focus on wavenumber region of 1700-1071 cm, and no preprocessed where PCA was applied on the whole spectra range of mid-FTIR. The results suggest that applying PCA on specified preprocessed spectra could detect hidden relationships between variables in chicken and beef in both approaches. PCA successfully clustered these kinds of meats when applied on transmission mode spectra without any preprocessing treatment, while applying it on ATR mode's raw spectra failed to cluster them. Additionally, the preprocessed ATR-FTIR spectrum was used to prepare regression models by Partial Least Square Regression (PLS-R) and artificial neural networks (ANN) for predicting presence and percentage of chicken meat in the beef meat mixture. The results demonstrated the superiority of ANN over PLS-R in this assessment with an R2 of 0.999.
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http://dx.doi.org/10.1007/s13197-019-04178-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054551PMC
April 2020

Toxicity of multi-wall carbon nanotubes inhalation on the brain of rats.

Environ Sci Pollut Res Int 2020 Apr 27;27(11):12096-12111. Epub 2020 Jan 27.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, P.O. Box: 14155-6153, Tehran, Iran.

This study was designed to investigate the brain toxicity following the respiratory contact with multi-wall carbon nanotubes (MWCNTs) in male Wistar rats. Rats were exposed to 5 mg/m MWCNT aerosol in different sizes and purities for 5 h/day, 5 days/week for 2 weeks in a whole-body exposure chamber. After 2-week exposure, mitochondrial isolation was performed from different parts of rat brain (hippocampus, frontal cortex, and cerebellum) and parameters of mitochondrial toxicity including mitochondrial succinate dehydrogenase (SDH) activity, generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release, ATP level, mitochondrial GSH, and lipid peroxidation were evaluated. Our results demonstrated that MWCNTs with different characteristics, in size and purity, significantly (P < 0.05) decreased SDH activity, GSH, and ATP level, and increased mitochondrial ROS production, lipid peroxidation, mitochondrial swelling, MMP collapse, and cytochrome c release in the brain mitochondria. In conclusion, we suggested that MWCNTs with different characteristics, in size and purity, induce damage in varying degrees on the mitochondrial respiratory chain and increase mitochondrial ROS formation in different parts of rat brain (hippocampus, frontal cortex, and cerebellum).
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http://dx.doi.org/10.1007/s11356-020-07740-5DOI Listing
April 2020

Generation and molecular docking analysis of specific single-chain variable fragments selected by phage display against the recombinant nucleocapsid protein of fig mosaic virus.

J Virol Methods 2020 02 5;276:113796. Epub 2019 Dec 5.

Istituto Agronomico Mediterraneo di Bari, Via Ceglie 9, 70010, Valenzano, BA, Italy. Electronic address:

The mosaic disease caused by fig mosaic virus (FMV) is considered the plague of fig worldwide. A naïve phage display library, raised against the recombinant nucleocapsid protein of FMV (FMV-Np) was screened to obtain specific monoclonal recombinant antibodies in the form of single chain variable fragments (scFvs). After three rounds of biopanning, the bacterially expressed FMV-Np was used as an antigen for selecting specific phages for the production of specific soluble scFvs to be used in immunological assays. The binding specificity of scFvs against FMV-infected fig samples was evaluated by immunoblotting and Plate trapped antigen-ELISA (PTA-ELISA), which revealed efficient of the resultant scFvs to the target antigen. Silico homology-modelling and molecular docking analysis confirmed the scFv and FMV-Np interactions with the anti-FMV-Np scFv through an estimated binding energy of -650 kj mol; considered to be generated from the interactions between 13 amino acids residues predicted as putative epitopes in the interface pocket of FMV-Np and scFv antibody. This high affinity was further confirmed in the specificity of ELISA and immunoblotting assays. This is the first report on the application of phage display technology to generate specific recombinant scFvs against FMV that can be applied in development of antibody-mediated protection strategy to control the fig mosaic disease.
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http://dx.doi.org/10.1016/j.jviromet.2019.113796DOI Listing
February 2020

Analysis of apoptosis related genes in nurses exposed to anti-neoplastic drugs.

BMC Pharmacol Toxicol 2019 12 2;20(1):74. Epub 2019 Dec 2.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Anti-neoplastic agents are widely used in the treatment of cancer and some non-neoplastic diseases. These drugs have been proved to be carcinogens, teratogens, and mutagens. Concern exists regarding the possible dangers of the staff handling anti-cancer drugs. The long-term exposure of nurses to anti-neoplastic drugs is still a controversial issue. The purpose of this study was to monitor cellular toxicity parameters and gene expression in nurses who work in chemotherapy wards and compare them to nurses who work in other wards.

Methods: To analyze the apoptosis-related genes overexpression and cytotoxicity effects, peripheral blood lymphocytes obtained from oncology nurses and the control group.

The Results: Significant alterations in four analyzed apoptosis-related genes were observed in oncology nurses. In most individual samples being excavated, Bcl-2 overexpression is superior to that of Bax. Prominent P53 and Hif-1α up-regulation were observed in oncology nurses. Moreover, all cytotoxicity parameters (cell viability, ROS formation, MMP collapse, Lysosomal membrane damage, Lipid peroxidation, Caspase 3 activity and Apoptosis phenotype) in exposed oncology nurses were significantly (p < 0.001) higher than those of unexposed control nurses. Up-regulation of three analyzed apoptosis-related genes were observed in nurses occupationally exposed to anti-cancer drugs.

Conclusion: Our data show that oxidative stress and mitochondrial toxicity induced by anti-neoplastic drugs lead to overexpression of apoptosis-related genes in oncology nurses.
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http://dx.doi.org/10.1186/s40360-019-0372-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889625PMC
December 2019

Assessing the risk of main activities of nanotechnology companies by the NanoTool method.

Int J Occup Saf Ergon 2020 Feb 19:1-9. Epub 2020 Feb 19.

Air Pollution Research Center, Iran University of Medical Sciences, Iran.

. Nanotechnology can be considered one of the greatest developments over the past few decades. Despite many applications of nanomaterials in various fields, there are concerns about their effects on humans and the environment. Therefore, this study was conducted to assess the risk level of activities involving nanomaterials in nanotechnology companies in Tehran, Iran. . After identifying the main activities of 18 nanotechnology companies, these activities were assessed using the NanoTool method, which is a method for assessing risks of activities involving nanomaterials. Data were analyzed using SPSS version 22. . The results showed that in six activities (33.30%) the risk level was 4 (RL4), in eight activities (44.40%) the risk level was 3 (RL3) and four activities (22.30%) had risk level 2 (RL2). Also, it was found that 78.88% of the controls used by these companies were not enough to reduce the risks of nanomaterials and need to be upgraded. . The high level of risk in the activities involving nanomaterials shows that there are serious problems regarding the safety of nanomaterials in the nanotechnology companies in Tehran, Iran.
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http://dx.doi.org/10.1080/10803548.2019.1693778DOI Listing
February 2020

FTIR bio-spectroscopy scattering correction using natural biological characteristics of different cell lines.

Analyst 2019 Sep;144(19):5810-5828

Department of Toxico/Pharmacology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Niayesh Highway, Valiasr Ave, Tehran, Iran.

Fourier transform infrared (FTIR) spectroscopy is a well-known method of analysis, with various applications, including promising potential for analyzing biological samples. In the bio-spectroscopy of cells, Mie scattering may increase, which then causes spectral distortion, due to the similarity of cell size with the IR medium-wavelength. These changes make the spectrum unreliable. In previous scattering elimination studies, questionable estimations were considered. For instance, all cells were considered as spherical objects or cell size was estimated randomly. In an attempt to provide the best equation based on the natural existence of cells for the FTIR Mie scattering correction, we examined the actual biological data of cells - as opposed to those yielded from mathematical manipulations. So five biological factors: cell size, shape, granularity, circularity, and edge irregularities, for each cell line were considered as factors which cause scattering. For measuring cell size, roundness and edge irregularity, microscopy images were obtained and processed. For evaluating cell line granularity, flow cytometry was used. Finally, by including these factors, an algorithm was designed. To assess the accuracy of the proposed algorithm, the trypsinized cell spectrum was considered as the high scattering spectrum. Cells were also cultured on a MirrIR slide, and their ATR-FTIR spectrum was considered as the minimum scattering spectrum. The algorithm using the abovementioned five characteristics was used for 13 different cell lines, and in some cases the corrected spectrum demonstrated more than 97% resemblance with the ATR spectra of the same cells. A comparison between the results of this algorithm with the Bassan et al. (2017) algorithm for scattering correction that is freely available on the Internet was then conducted on two different cell lines, clearly showing the advantages of our algorithm, in terms of accuracy and precision. Therefore, this method can be viewed as a more suitable solution for scattering correction in cell investigations.
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http://dx.doi.org/10.1039/c9an00811jDOI Listing
September 2019

Optimization of induction parameters, structure quality assessment by ATR-FTIR and in silico characterization of expressed recombinant polcalcin in three different strains of Escherichia coli.

Int J Biol Macromol 2019 Oct 11;138:97-105. Epub 2019 Jul 11.

Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran. Electronic address:

The inhalation of Chenopodium album (C. album) pollen, especially polcalcin (Che a 3), has been reported as a significant source of allergic respiratory symptoms. This study was conducted to characterize biophysical differences of recombinant polcalcin come from three different Escherichia coli strains using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), optimize recombinant polcalcin expression, and linear B-cell epitopes identification using in silico methods. ATR-FTIR results of purified proteins showed spectra intensity variance in the amide I region, while there were no changes in pick position and shape of the bands. SHuffle® T7 Express was selected for subsequent optimization due to ability in the correction of the mis-oxidized bonds and promotes proper folding which was validated by ATR-FTIR analysis results. Then, Response Surface Methodology was performed to optimize critical factors including induction temperature, duration of induction, and concentration of inducer. The best partitioning conditions were achieved in 1.5 mM IPTG for 10.97 h at 29.9 °C. Finally, prediction of polcalcin B-cell epitopes was carried out which indicated the presence of 4 different epitopes. Together, the results may help to the development of diagnostic approaches and also vaccine manufacture for desensitization and modulation of the allergic response in patients.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.07.078DOI Listing
October 2019

Functionalisation of carbon nanotubes by methotrexate and study of synchronous photothermal effect of carbon nanotube and anticancer drug on cancer cell death.

IET Nanobiotechnol 2019 Feb;13(1):52-57

Department of Toxicology and Pharmacology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Carboxylated functionalised multi-walled carbon nanotubes (f-MWCNT) were synthesised. Furthermore, folic acid (FA) and methotrexate (MTX) through ethylenediamine (ED) were attached to the surface of f-MWCNT to synthesise MWCNT-ED-FA and MWCNT-ED-MTX. Release studies of MTX as free drug and in MWCNT-ED-MTX were performed. These studies showed that MTX release rate from MWCNT-ED-MTX decreased in comparison with free MTX, which is due to the MTX attachment on the MWCNT. The anticancer effect of MWCNT-ED-FA and MWCNT-ED-MTX on the breast cancer cell line (MCF-7) was studied. Studies have shown that MWCNT-ED-MTX cytotoxicity is more than that of MWCNT-ED-FA, which is due to the presence of MTX. Furthermore, the anticancer effects of MWCNT-ED-FA and MWCNT-ED-MTX in the presence of infrared laser radiation on the MCF7 cell were studied. The experiments showed that in the presence of the laser, the cytotoxicities of MWCNT-ED-FA and MWCNT-ED-MTX were the same and increased in comparison with laser absence, which indicates that the photothermal effect is stronger than other factors and mask their effects. This effect can be related to laser radiation absorption by MWCNT and its conversion to heat which can induce cancer cell death. Targeting studies have shown that MWCNT-ED-FA is targeted to the cancer cells due to the presence of FA.
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http://dx.doi.org/10.1049/iet-nbt.2018.5085DOI Listing
February 2019

Combination of static magnetic field and cisplatin in order to reduce drug resistance in cancer cell lines.

Int J Radiat Biol 2019 08 21;95(8):1194-1201. Epub 2019 Mar 21.

a Toxicology Research Center and Department of Toxicology, School of Pharmacy and, Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran.

In this study, the effects of different intensities of Static Magnetic Fields (SMFs) (10, 15 and 25 mT) and different concentrations of cisplatin drug were investigated on the viability percent and IC of the A2780 and A2780-CP cell lines at 24, 48 and 96 h to show useful potential of SMF as a physical agent to enhance the effectiveness of common therapeutic approaches and decrease of drug resistance to cisplatin anticancer drug. Magnetic field exposure was performed using a locally designed generator. The cell viability percent, IC and cisplatin uptake in treated cells were evaluated by MTT assay and inductively coupled plasma (ICP), respectively. Increasing of concentration and time of cisplatin drug showed a noticeable decrease in viability percent in sensitive and resistant cell lines compared with control group. These decreases were more significant in resistant cells compared with sensitive cells. The obtained IC values for resistant were greater than the values obtained for A2780 cells. ICP analysis demonstrated an increased uptake of cisplatin after treatment for 48 and 96 h relative to untreated groups in both resistant and sensitive cells. Results showed that A2780 cells were more sensitive to cisplatin than A2780-CP. Studies have shown that SMF can increase the effect of cisplatin on cell viability percent and decrease the resistance of A2780-CP cells by producing large, verruca shaped structures at the surface of the cell membrane.
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http://dx.doi.org/10.1080/09553002.2019.1589012DOI Listing
August 2019

A comparative study of the bispecific monoclonal antibody, blinatumomab expression in CHO cells and E. coli.

Prep Biochem Biotechnol 2018 21;48(10):961-967. Epub 2018 Nov 21.

b Biotechnology Research Center , Pasteur Institute of Iran , Tehran , Iran.

The "bispecifics" market improved over the past decade due to the development of many technological platforms including bispecific T cell engagers (BiTEs). The approval of blinatumomab, the most advanced bispecific T-cell engager (BiTE) in clinical trials, can be a significant milestone in the development of bispecific antibodies. Both Chinese hamster ovary (CHO) cells and E. coli strain are considered as the most widely used hosts for the large-scale production of therapeutic monoclonal antibodies. Since both of the economic and qualitative aspects of protein production are important in industry, selection of a suitable protein expression system is very critical. The BsAb gene was cloned into the expression vectors FC550A-1, pcDNA3.1 (+), and PET22b and 6 × His-tagged BsAb then purified on a Ni-NTA chromatography column. Both SDS-PAGE and Western blotting analysis of the purified protein demonstrated that blinatumomab was successfully expressed as a 55 kDa in both expression systems. The antigen-binding properties of blinatumomab were compared in the mammalian system versus Escherichia coli. The results showed that the purified antibody from a mammalian expression system has better binding activity than the one from E. coli host.
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http://dx.doi.org/10.1080/10826068.2018.1525562DOI Listing
February 2019

Arizona Ridge-nosed rattlesnake envenomation: Case report of a personal encounter with the official state reptile of Arizona, Crotalus willardi willardi.

Toxicon 2018 Sep 6;151:84-88. Epub 2018 Jul 6.

Arizona Poison and Drug Information Center, Tucson, AZ, USA; Banner University Medical Center, Tucson, AZ, USA.

This case report describes the effects of an envenomation from one of the most infrequently encountered species of rattlesnake in the United States, Crotalus willardi willardi (C. w. willardi), the Arizona Ridge-nosed Rattlesnake. A previously healthy 57-year-old male sustained a bite to his non-dominant hand from a C. w. willardi. The most pronounced effect from the envenomation was edema and progression of edema that extended from his hand to the mid bicep. He also experienced erythema and tenderness to palpation in the affected limb, and some diminished range of motion in the hand. He expressed only minimal pain. Other than a mildly positive D-Dimer and leukocytosis, he had no significant hematologic effects and no systemic effects. He was treated with standard doses of Crotalidae Polyvalent Immune Fab (Ovine). He reported complete recovery from the envenomation within three days of the bite. Although envenomation from rattlesnakes is somewhat common in Arizona, knowing the exact species of snake is not. Confirmed documentation is exceedingly rare as most people do not recognize the different rattlesnake species. In addition, some species of rattlesnake (such as C. w. willardi) are especially reclusive and found only in isolated mountainous regions. Being able to confirm an envenomation by C. w. willardi would require not only someone knowledgeable in herpetology, but also, preferably, photographic evidence. This case has both.
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http://dx.doi.org/10.1016/j.toxicon.2018.07.001DOI Listing
September 2018

Influence of formulation of ZnO nanoblokes containing metallic ions dopants on their cytotoxicity and protective factors: An in vitro study on human skin cells exposed to UVA radiation.

Toxicol Rep 2018 6;5:468-479. Epub 2018 Mar 6.

Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Application of ZnO nanoparticles in sunscreens exposes human skin with their adverse effects, which correlates to dissolution/translocation of free Zn ions. The possibility of decreasing solubility and therefore, reducing toxicity, by structural modifications have been discussed as a solution. The present investigation has developed new metallic lattices of ZnO to reduce cytotoxicity of ZnO nanoparticles. Novel metal-promoted Zn-based nanocomposites ([Zn(O)/M], M = Mg, Al, Ca, Ti) were synthesized and their physicochemical properties and their cytotoxicity were evaluated. Solubility and release studies showed that modification of ZnO structure decreases release of Zn into culture medium. XRD and UV absorbance analyses showed that metallic-dopants percolate into crystalline lattice of ZnO. This phenomenon is basic reason for stability of Zn-based network. Cell culture studies and MTT assay on human skin cells (HFF-1) exposed to UVA radiation showed that the level of protection of [Zn(O)/M] compounds were more than of [ZnO]. Dichlorofluoroscein diacetate-ROS assay and Zn release experiments indicated that [Zn(O)/M] nanocomposites decreased the level of ROS generation and Zn release in compared to ZnO, indicating higher safety of nanocomposites. This study shows that the synthesized Zn-based nanocomposites have potential to be used as safer and more effective sunscreens than ZnO.
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http://dx.doi.org/10.1016/j.toxrep.2018.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977415PMC
March 2018

Evaluation of Silibinin Effects on the Viability of HepG2 (Human hepatocellular liver carcinoma) and HUVEC (Human Umbilical Vein Endothelial) Cell Lines.

Iran J Pharm Res 2018 ;17(1):261-267

Cancer research Center, Shohadae Tajrish Hospital, Department of Radiation Oncology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Human hepatocellular carcinoma is one of the most common recurrent malignancies since there is no effective therapy for it. Silibinin, a widely used drug and supplement for various liver disorders, demonstrated anti-cancer effects on human hepatocellular carcinoma, human prostate adenocarcinoma cells, human breast carcinoma cells, human ectocervical carcinoma cells, and human colon cancer cells. Considering the anti-hepatotoxic activity of silibinin and its strong preventive and anti-cancer efficacy against various epithelial cancers, we investigated the efficacy of silibinin against human HCC and HUVEC cell lines. Silibinin effects on the growth and mode of cell death of these two cell lines are presented in this paper. HepG2 and HUVEC cells were incubated with different doses of silibinin (12.5, 25, 50, 100, 150 and 200 μg/mL) at 24, 48, and 72 h. Cytotoxicity was assessed using MTT and Trypan blue assays. Mode of cell death induced by silibinin was investigated using LDH assay and acridine orange/PI double dye staining. The results showed that silibinin has dose-dependent inhibitory effect on the viability of HepG2 and HUVEC cells. However, Silibinin causes a more continuous dose-dependent cytotoxicity in HepG2 cells compared to the HUVEC cells in which some degrees of resistance is apparent at the beginning. The mode of cell death looks also different in these two cell lines with HepG2 cells being more in favor of apoptosis while necrosis is more evident for the HUVEC cells.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937096PMC
January 2018

Ag-promoted zinc oxide [Zn(O):Ag]: A novel structure for safe protection of human skin against UVA radiation.

Toxicol In Vitro 2018 Aug 2;50:318-327. Epub 2018 Mar 2.

Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Different sunscreens are employed to prevent photo damage (cancer, inflammation, etc.), including ZnO. ZnO is safe when applied as micro-size particle. To overcome some visual problems of ZnO micro-size particles, this sunscreen has been introduced as nano-size particles. Unfortunately, ZnO nanoparticles have raised some health concerns, due to Zn release. On the other hand, it has been shown that ZnO metallic lattice change by metal doping decreases its solubility and toxicity. Therefore, we have decided here to develop new ZnO metallic lattice to reduce its cytotoxicity. In this study, Ag-promoted Zn-based nanocompounds [Zn(O):Ag] were synthesized as a novel compound and were characterized. XRD analysis showed that Ag ion percolates into ZnO crystalline lattice and changes its lattice properties (strength bond, vacancies, and etc.). Cell culture studies and MTT assay on human skin (HFF-1) cells exposed to UVA radiation showed that [Zn(O):Ag] was increased cells viability in the presence of UVA radiation compared to ZnO. Actually, Ag ion has catalyzed photoactivity of ZnO compound. UV-blocking tests showed that UVA-absorbance of [Zn(O):Ag] has increased compared to ZnO. Dichlorofluoroscein diacetate-ROS assay and Zn release experiments in the presence of cells showed that [Zn(O):Ag] has reduced Zn ions release into culture medium and its toxicity. Our study shows that doped ZnO nanostructure has the potential to be applied as a safe and effective nanoparticulate sunscreen.
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http://dx.doi.org/10.1016/j.tiv.2018.02.016DOI Listing
August 2018

Mercury Poisoning in a Toddler from Home Contamination due to Skin-Lightening Cream.

J Pediatr 2018 05 13;196:314-317.e1. Epub 2018 Feb 13.

Arizona Poison and Drug Information Center, University of Arizona, Tucson, AZ.

A 17-month-old child presented with hypertension, fussiness, constipation, and arthralgia due to mercury toxicity from a skin-lightening cosmetic used by her mother and grandmother. Blood mercury level was 26 mcg/L and urine level was 243 mcg/g creatinine. She was chelated with succimer. The home was contaminated and needed remediation.
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http://dx.doi.org/10.1016/j.jpeds.2017.12.023DOI Listing
May 2018
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