Publications by authors named "Andreea Letitia Arsene"

12 Publications

  • Page 1 of 1

Thrombosis and Haemostasis challenges in COVID-19 - Therapeutic perspectives of heparin and tissue-type plasminogen activator and potential toxicological reactions-a mini review.

Food Chem Toxicol 2021 Feb 6;148:111974. Epub 2021 Jan 6.

Oncology Department, Elias Emergency Hospital, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.

The coronavirus disease (COVID)-19 pandemic is a major challenge for the health systems worldwide. Acute respiratory distress syndrome (ARDS), is one of the most common complications of the COVID-19 infection. The activation of the coagulation system plays an important role in the pathogenesis of ARDS. The development of lung coagulopathy involves thrombin generation and fibrinolysis inhibition. Unfractionated heparin and its recently introduced counterpart low molecular weight heparin (LMWH), are widely used anticoagulants with a variety of clinical indications allowing for limited and manageable physio-toxicologic side effects while the use of protamine sulfate, heparin's effective antidote, has made their use even safer. Tissue-type plasminogen activator (tPA) is approved as intravenous thrombolytic treatment. The present narrative review discusses the use of heparin and tPA in the treatment of COVID-19-induced ARDS and their related potential physio-toxicologic side effects. The article is a quick review of articles on anticoagulation in COVID infection and the potential toxicologic reactions associated with these drugs.
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http://dx.doi.org/10.1016/j.fct.2021.111974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837001PMC
February 2021

Heavy metal and pesticide levels in dairy products: Evaluation of human health risk.

Food Chem Toxicol 2020 Dec 3;146:111844. Epub 2020 Nov 3.

Department of Biostatistics, Faculty of Pharmacy, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania. Electronic address:

Cattle milk's health benefits can be compromised by the presence of contaminants. The levels of cadmium, copper, lead and zinc, and residues of dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyldichloroethane (DDD), dichlorodiphenyltrichloroethane (DDT) were determined in soil, milk and cheese samples collected from cow farms from 3 Romanian areas with industrial and agriculture tradition. A new methodology was applied for the determination of the corrected estimated daily intake (cEDI) corresponding to the aggregate dietary exposure. For the risk assessment, we calculated the source hazard quotient (HQs) for each contaminant and the adversity specific hazard index (HIA). Cadmium, copper, lead and zinc, and the sum of DDT levels in soil samples were below maximum residue levels (MRLs). The MRLs of lead and DDD were exceeded in milk and cheese samples from all the 3 areas. The MRLs of copper and zinc were exceeded in cheese samples from area 2 and 3. HQs >10 for lead indicates increased risk, while HQ > 1 for copper and sum of DDT indicates moderate risk for both milk and cheese. By calculating the HI, we identified a moderate and increase risk for nephrotoxicity, hepatotoxicity, hematotoxicity, cardiotoxicity and reproduction toxicity after consumption of the dairy products from the 3 areas.
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http://dx.doi.org/10.1016/j.fct.2020.111844DOI Listing
December 2020

Recent advances, approaches and challenges in targeting pathways for potential COVID-19 vaccines development.

Immunol Res 2020 12 1;68(6):315-324. Epub 2020 Oct 1.

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

During the COVID-19 pandemic in a modern era, there is a global consensus on the need for the rapid development of a vaccine against SARS-CoV-2 for effective and sustainable control. Developing these vaccines is fundamental to public health. This urgent need is supported by the scientific explosion in structural and genomic biology that facilitates the urgent development of an ideal COVID-19 vaccine, using new pathways to facilitate its large-scale development, testing, and manufacture. Here, we summarize the types of COVID-19 candidate vaccines, their current stage in early testing in human clinical trials, and the challenges for their implementation.
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http://dx.doi.org/10.1007/s12026-020-09154-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529090PMC
December 2020

Adverse and hormetic effects in rats exposed for 12 months to low dose mixture of 13 chemicals: RLRS part III.

Toxicol Lett 2019 Aug 16;310:70-91. Epub 2019 Apr 16.

Center of Toxicology Science & Research, Medical School, University of Crete, Heraklion, Crete, Greece; Department of Analytical and Forensic Medical Toxicology, Sechenov University, Moscow 119991, Russian Federation. Electronic address:

The aim of the current study was to evaluate the effects of a mixture of thirteen common chemicals on rats, after a one-year exposure to doses around the acceptable daily intake (ADIs), using blood and urinary tests. The influence of low doses of the mixture on weight gain, water consumption, feed consumption and feed efficiency, biochemistry parameters, haematological parameters, blood lymphocytes subsets, serum inflammation profile and urine parameters was evaluated. Our mixture caused a moderate monotonic increase of the males' appetite and a non-monotonic increase of anabolism and a monotonic increase of appetite for the females. Regarding biochemical parameters, the exposure to the test mixture caused non-monotonic increases of AST and ALT, a decrease of PChE in males and plausibly a monotonic biliary obstruction in both sexes. Monocytes significantly increased in low dose groups of both sexes. A significant decrease of all the lymphocytes subclasses and an increased expression of TNF-α protein associated with an increased expression of IFN-γ protein observed in various groups. It became apparent that after twelve months of exposure very low doses of the tested mixture had both non-monotonic and monotonic harmful effects on different levels on rats.
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http://dx.doi.org/10.1016/j.toxlet.2019.04.005DOI Listing
August 2019

Strategies for Improving Ocular Drug Bioavailability and Corneal Wound Healing with Chitosan-Based Delivery Systems.

Polymers (Basel) 2018 Nov 3;10(11). Epub 2018 Nov 3.

Department of Physical and Colloidal Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy "Carol Davila", Bucharest 020956, Romania.

The main inconvenience of conventional eye drops is the rapid washout of the drugs due to nasolacrimal drainage or ophthalmic barriers. The ocular drug bioavailability can be improved by either prolonging retention time in the cul-de-sac or by increasing the ocular permeability. The focus of this review is to highlight some chitosan-based drug delivery approaches that proved to have good clinical efficacy and high potential for use in ophthalmology. They are exemplified by recent studies exploring in-depth the techniques and mechanisms in order to improve ocular bioavailability of the active substances. Used alone or in combination with other compounds with synergistic action, chitosan enables ocular retention time and corneal permeability. Associated with other stimuli-responsive polymers, it enhances the mechanical strength of the gels. Chitosan and its derivatives increase drug permeability through the cornea by temporarily opening tight junctions between epithelial cells. Different types of chitosan-based colloidal systems have the potential to overcome the ocular barriers without disturbing the vision process. Chitosan also plays a key role in improving corneal wound healing by stimulating the migration of keratinocytes when it is used alone or in combination with other compounds with synergistic action.
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http://dx.doi.org/10.3390/polym10111221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290606PMC
November 2018

CYP polymorphisms and pathological conditions related to chronic exposure to organochlorine pesticides.

Toxicol Rep 2017 26;4:335-341. Epub 2017 May 26.

Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Greece.

The association between genetic variations in the cytochrome P450 (CYP) family genes and pathological conditions related to long-term exposure to organochlorine compounds (OCs) deserves further elucidation. OCs are persistent organic pollutants with bioaccumulative and lipophilic characteristics. They can act as endocrine disruptors and perturb cellular mechanisms. Prolonged exposure to OCs has been associated with different pathological manifestations. CYP genes are responsible for transcribing enzymes essential in xenobiotic metabolism. Therefore, polymorphisms in these genetic sequences a. alter the metabolic pathways, b. induce false cellular responses, and c. may provoke pathological conditions. The main aim of this review is to define the interaction between parameters a, b and c at a mechanistic/molecular level, with references in clinical cases.
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http://dx.doi.org/10.1016/j.toxrep.2017.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615117PMC
May 2017

Therapeutic potential of certain drug combinations on paclitaxel-induced peripheral neuropathy in rats.

Rom J Morphol Embryol 2017 ;58(2):507-516

Department of Pharmacodynamics and Clinical Pharmacy, Faculty of Pharmacy, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania;

Background And Aims: Experimental research and clinical data support the potential combination therapy for the treatment of neuropathic pain. We aimed to investigate the analgesic effect of the following associations: gabapentin + etifoxine; tramadol + etifoxine; gabapentin + tramadol, in an experimental model of peripheral neuropathy induced by paclitaxel.

Materials And Methods: Neuropathy was induced in male Wistar rats by the daily administration of 2 mg÷kg body weight (bw) paclitaxel intraperitoneally, four days in a row. Analgesics were given concomitantly with paclitaxel, in the following doses: tramadol 15 mg÷kg bw, etifoxine 100 mg÷kg bw, gabapentin 300 mg÷kg bw. Tactile allodynia and mechanical hyperalgesia were assessed using the Dynamic Plantar Aesthesiometer apparatus (Ugo Basile). After 18 days of treatment, the brain and liver tissue susceptibility to lipid peroxidation was evaluated and the sciatic nerve histological examination of the effect on myelin fibers was performed.

Results And Conclusions: Experimental data have shown a strong analgesic effect of these three tested combinations expressed mainly by the statistically significant increased maximum response time, both in the assessment of allodynia and hyperalgesia. The gabapentin + tramadol combination lead to the maximum analgesic effect, immediately after the discontinuation of paclitaxel (44.94%, p<0.0001) and throughout the study. The treatment associated with tramadol caused a reduction in lipid peroxidation in the brain as compared to paclitaxel group. Combination therapy showed reduced damage to myelinated fiber density in the sciatic nerve. The drug combinations used in the experiment showed therapeutic potential in the fight against neuropathic pain induced by the administration of taxanes.
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April 2018

Pharmacological management of non-alcoholic fatty liver disease: Atorvastatin versus pentoxifylline.

Exp Ther Med 2017 May 23;13(5):2375-2381. Epub 2017 Mar 23.

Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, Craiova 200349, Romania.

In this study, we aimed to evaluate the efficacy of pentoxifylline and atorvastatin in the treatment of non-alcoholic fatty liver disease (NAFLD). The study included 98 patients with histologically confirmed NAFLD divided into 2 groups as follows: group I (57 dyslipidemic patients, receiving atorvastatin 20 mg/day and group II (41 non-dyslipidemic patients, treated with pentoxifylline, 800 mg/day). The present study was conducted for a mean of 32.8±3.4 weeks. For all patients, we determined the body mass index, a liver biopsy was performed, and we measured the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total cholesterol (TC) and triglycerides (TG) at the beginning and at the end of the study period. The NAFLD activity score (NAS) was used to evaluate the liver biopsies for steatosis, fibrosis and necroinflammation. The patients in group I exhibited a considerable reduction in ALT, AST, GGT, TC, AP and TG levels (P<0.0001). Histologically, there were no changes in fibrosis and necroinflammation, although the extent steatosis was reduced. The improvement in the ALT, AST and GGT values (P<0.05) in group II were similar to those in group I; however, no statistically significant decrease was noted in the levels of ALP, TC and TG in this group. Our results thus demonstrated that atorvastatin attenuated steatosis and improved liver function parameters in patients with NAFLD associated with dyslipidemia. Similar results were obtained in the non-dyslipidemic patients administered pentoxifylline.
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http://dx.doi.org/10.3892/etm.2017.4256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443168PMC
May 2017

Pharmacological management of non-alcoholic fatty liver disease: Atorvastatin versus pentoxifylline.

Exp Ther Med 2017 May 23;13(5):2375-2381. Epub 2017 Mar 23.

Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, Craiova 200349, Romania.

In this study, we aimed to evaluate the efficacy of pentoxifylline and atorvastatin in the treatment of non-alcoholic fatty liver disease (NAFLD). The study included 98 patients with histologically confirmed NAFLD divided into 2 groups as follows: group I (57 dyslipidemic patients, receiving atorvastatin 20 mg/day and group II (41 non-dyslipidemic patients, treated with pentoxifylline, 800 mg/day). The present study was conducted for a mean of 32.8±3.4 weeks. For all patients, we determined the body mass index, a liver biopsy was performed, and we measured the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total cholesterol (TC) and triglycerides (TG) at the beginning and at the end of the study period. The NAFLD activity score (NAS) was used to evaluate the liver biopsies for steatosis, fibrosis and necroinflammation. The patients in group I exhibited a considerable reduction in ALT, AST, GGT, TC, AP and TG levels (P<0.0001). Histologically, there were no changes in fibrosis and necroinflammation, although the extent steatosis was reduced. The improvement in the ALT, AST and GGT values (P<0.05) in group II were similar to those in group I; however, no statistically significant decrease was noted in the levels of ALP, TC and TG in this group. Our results thus demonstrated that atorvastatin attenuated steatosis and improved liver function parameters in patients with NAFLD associated with dyslipidemia. Similar results were obtained in the non-dyslipidemic patients administered pentoxifylline.
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http://dx.doi.org/10.3892/etm.2017.4256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443168PMC
May 2017

Pharmacotoxicological screening on new derivatives of beta-phenylethylamine, potential agonists of beta3-adrenergic receptors.

Rom J Morphol Embryol 2016 ;57(3):969-978

Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Romania;

Background And Aims: Beta3-adrenergic receptors (beta3-ARs) have been initially characterized in 1989. Afterwards, their tissue distribution was established: white and brown adipose tissue, central nervous system, myocardium (atrial and ventricular), blood vessels, smooth gastrointestinal muscles (stomach, small intestine, colon), gallbladder, urinary bladder, prostate, skeletal muscles. Non-clinical trials have demonstrated the major implication of beta3-ARs in glucose metabolism, implicitly, in insulin release, and also in obesity. Therefore, new compounds were synthesized starting from beta-phenylethylamine nucleus and substituted in various positions, for possible antidiabetic and÷or antiobesity action.

Materials And Methods: In the present research, the antidiabetic action of newly synthesized compounds was investigated on an experimental model of alloxan-induced diabetes, administered in dose of 130 mg÷kg body weight (bw), intraperitoneally (i.p.). After 14 days of treatment, glycemia and enzymes involved in homeostasis of glucose metabolism, glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase (G6Pase) and hexokinase were determined. Animals were then euthanized and histopathology examinations were performed on harvested liver, kidney, spleen and brain in order to document pathological changes induced by alloxan-induced diabetes and÷or by tested compounds.

Results And Conclusions: Glycemia in animals treated with the tested compounds decreased statistically significant for groups C2 and C3 (-42.13% and -37.2%, respectively), compared to diabetic control group. C2 was also the compound to favorably modify the dynamics of determined enzymes, together with the display of very good safety profile supported by minor, non-significant, histopathological changes.
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May 2017

Antimicrobial resistance development following surgical site infections.

Mol Med Rep 2017 Feb 13;15(2):681-688. Epub 2016 Dec 13.

Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.

Surgical site infections (SSIs) determine an increase in hospitalization time and antibiotic therapy costs. The aim of this study was to identify the germs involved in SSIs in patients from the Clinical Emergency County Hospital of Craiova (SCJUC) and to assess their resistance to antimicrobials, with comparisons between surgical wards and the intensive care unit (ICU). The biological samples were subjected to classical bacteriological diagnostics. Antibiotic resistance was tested by disc diffusion. We used hierarchical clustering as a method to group the isolates based upon the antibiotic resistance profile. The most prevalent bacterial species isolated were Staphylococcus aureus (S. aureus; 50.72%), followed by Escherichia coli (E. coli; 17.22%) and Pseudomonas aeruginosa; 10.05%). In addition, at lower percentages, we isolated glucose-non-fermenting, Gram-negative bacteria and other Enterobacteriaceae. The antibiotic resistance varied greatly between species; the most resistant were the non-fermenting Gram‑negative rods. E. coli exhibited lower resistance to third generation cephalosporins, quinolones and carbapenems. By contrast, Klebsiella was resistant to many cephalosporins and penicillins, and to a certain extent to carbapenems due to carbapenemase production. The non-fermenting bacteria were highly resistant to antibiotics, but were generally sensitive to colistin. S. aureus was resistant to ceftriaxone (100%), penicillin (91.36%), amoxicillin/clavulanate (87.50%), amikacin (80.00%) and was sensitive to levofloxacin, doxycycline, gentamycin, tigecycline and teicoplanin. The Enterobacteriaceae resistance was only slightly higher in the ICU, particularly to carbapenems (imipenem, 31.20% in the ICU vs. 14.30% in the surgical wards; risk ratio = 2.182). As regards Staphylococcus species, but for non-fermenting bacteria, even if the median was almost the same, the antibiotic resistance index values were confined to the upper limit in the ICU. The data gathered from this study may help infection control teams to establish effective guidelines for antibiotic therapies in various surgical procedures, in order to minimize the risk of developing SSIs by the efficient application of the anti-infection armamentarium.
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http://dx.doi.org/10.3892/mmr.2016.6034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364857PMC
February 2017

Behavioral and molecular effects of prenatal continuous light exposure in the adult rat.

Brain Res 2016 11 24;1650:51-59. Epub 2016 Aug 24.

Division of Physiology and Fundamental Neuroscience, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. Electronic address:

Disruption of the maternal environment during pregnancy leads to behavioral changes and diseases in the adult offspring. To explore the influence of prenatal continuous light exposure (PCLE) on the adult offspring, we exposed pregnant Wistar rats to constant light during late gestation. Adult PCLE offspring showed an anxiety-like behavior and impairment of short-term memory in different tests. Measurements in the whole brain homogenates from newborn and adult offspring indicated decreased melatonin and serotonin levels and increased reactive oxygen species level in PCLE offspring. Further, we determined melatonin-, serotonin-, oxidative stress-, apoptosis-, and circadian system-related genes expression in different brain areas of adult offspring. The serotonin reuptaker Slc6a4 displayed a decreased expression in the prefrontal cortex of PCLE group. The circadian rhythm-related gene Rora was upregulated in the amygdala of PCLE offspring. Our results point to adverse behavioral effects of PCLE on adult offspring, involving serotonin and melatonin signaling dysregulation, increased chronic oxidative stress, and altered gene expression.
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http://dx.doi.org/10.1016/j.brainres.2016.08.031DOI Listing
November 2016