Search results for: common drug combinations

Authors: Ersumo Tessema, Bogale Girmaye Tamrat, Mohammed Burka

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Background: Hyperthyroidism is a common thyroid disorder especially in women and characterized by increased thyroid hormone synthesis and secretion. The disorder manifests predominantly as Graves’ disease in iodine-sufficient areas and has increasing prevalence in iodine-deficient countries in patients with nodular thyroid disease and following iodine fortification. In Ethiopia, the magnitude of the disorder is unknown and, in Africa, due to scarcity of resources, its management remains suboptimal. Objective: The aim of this study was to analyze the pattern and management of patients with hyperthyroidism at the United Vision Medical Services Center, Addis Ababa between August 30, 2013, and February 1, 2018. Patients and methods: The study was a retrospective analysis of medical records of all patients with hyperthyroidism at the United Vision Private Medical Services Center, Addis Ababa. A questionnaire was filled out; the collected data entered into a computer and statistically analyzed using the SPSS package. The results were tabulated and discussed with literature review. Results: A total of 589 patients were included in this study. The median age was 40 years, and the male to female ratio was 1.0:7.9. Most patients (93%) presented with goiter and the associated features of toxic goiter except weight loss, sweating and tachycardia were uncommon. Majority of patients presented more than two years after the onset of their presenting symptoms. The most common physical finding (91%), as well as diagnosis, was toxic nodular goiter. The most frequent (83%) derangement in the thyroid function tests was a low thyroid-stimulating hormone, and the most commonly (94%) used antithyroid drug was a propylthiouracil. The most common (96%) surgical procedure in 213 patients was a near-total thyroidectomy with a postoperative course without incident in 92% of all the patients. Conclusion: The incidence and prevalence of hyperthyroidism are apparently on the increase in Addis Ababa, which may be related to the existing severe iodine-deficiency and or the salt iodation program (iodine-induced hyperthyroidism). Hyperthyroidism predominantly affects women and, in surgical services, toxic nodular goiter is more common than diffuse goiter, and the treatment of choice in experienced hands is a near-total thyroidectomy.

Keywords: Ethiopia, grave’s disease, hyperthyroidism, toxic nodular goiter

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Authors: Amber Dhoot, Tarush Gupta, Andrea Gurr, William Jenkins, Sandro Pietrunti, Alexis Tang

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Background: The COVID-19 pandemic has driven pharmacovigilance towards a new paradigm. Nowadays, more people than ever before are recognising and reporting adverse reactions from medications, treatments, and vaccines. In the modern era, with over 3.8 billion users, social media has become the most accessible medium for people to voice their opinions and so provides an opportunity to engage with more patient-centric and accessible pharmacovigilance. However, the pharmaceutical industry has been slow to incorporate social media into its modern pharmacovigilance strategy. This project aims to make social media a more effective tool in pharmacovigilance, and so reduce drug costs, improve drug safety and improve patient outcomes. This will be achieved by firstly uncovering and categorising the barriers facing the widespread adoption of social media in pharmacovigilance. Following this, the potential opportunities of social media will be explored. We will then propose realistic, practical recommendations to make social media a more effective tool for pharmacovigilance. Methodology: A comprehensive systematic literature review was conducted to produce a categorised summary of these barriers. This was followed by conducting 11 semi-structured interviews with pharmacovigilance experts to confirm the literature review findings whilst also exploring the unpublished and real-life challenges faced by those in the pharmaceutical industry. Finally, a survey of the general public (n = 112) ascertained public knowledge, perception, and opinion regarding the use of their social media data for pharmacovigilance purposes. This project stands out by offering perspectives from the public and pharmaceutical industry that fill the research gaps identified in the literature review. Results: Our results gave rise to several key analysis points. Firstly, inadequacies of current Natural Language Processing algorithms hinder effective pharmacovigilance data extraction from social media, and where data extraction is possible, there are significant questions over its quality. Social media also contains a variety of biases towards common drugs, mild adverse drug reactions, and the younger generation. Additionally, outdated regulations for social media pharmacovigilance do not align with new, modern General Data Protection Regulations (GDPR), creating ethical ambiguity about data privacy and level of access. This leads to an underlying mindset of avoidance within the pharmaceutical industry, as firms are disincentivised by the legal, financial, and reputational risks associated with breaking ambiguous regulations. Conclusion: Our project uncovered several barriers that prevent effective pharmacovigilance on social media. As such, social media should be used to complement traditional sources of pharmacovigilance rather than as a sole source of pharmacovigilance data. However, this project adds further value by proposing five practical recommendations that improve the effectiveness of social media pharmacovigilance. These include: prioritising health-orientated social media; improving technical capabilities through investment and strategic partnerships; setting clear regulatory guidelines using multi-stakeholder processes; creating an adverse drug reaction reporting interface inbuilt into social media platforms; and, finally, developing educational campaigns to raise awareness of the use of social media in pharmacovigilance. Implementation of these recommendations would speed up the efficient, ethical, and systematic adoption of social media in pharmacovigilance.

Keywords: adverse drug reaction, drug safety, pharmacovigilance, social media

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Authors: Eda Cagli, Irem Erel Goktepe

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Externally triggered and effective release of therapeutics from polymer nanoplatforms is one of the key issues in cancer treatment. In this study, we aim to prepare polymer multilayer films which are stable at physiological conditions (little or no drug release) but release drug molecules at acidic pH and via application of AC magnetic field. First, novel stimuli responsive diblock copolymers composed of pH- and temperature-responsive blocks were synthesized. Then, block copolymer micelles with pH-responsive core and temperature responsive coronae will be obtained via pH-induced self-assembly of these block copolymers in aqueous environment. A model anticancer drug, e.g. Doxorubicin will be loaded in the micellar cores. Second, superparamagnetic nanoparticles will be synthesized. Magnetic nanoparticles and drug loaded block copolymer micelles will be used as building blocks to construct the multilayers. To mimic the acidic nature of the tumor tissues, Doxorubicin release from the micellar cores will be induced at acidic conditions. Moreover, Doxorubicin release from the multilayers will be facilitated via magnetothermal trigger. Application of AC magnetic field will induce the heating of magnetic nanoparticles resulting in an increase in the temperature of the polymer platform. This increase in temperature is expected to trigger conformational changes on the temperature-responsive micelle coronae and facilitate the release of Doxorubicin from the surface. Such polymer platform may find use in biomedical applications.

Keywords: layer-by-layer films, magnetothermal trigger, smart polymers, stimuli responsive

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Authors: Leslie Raphael de M. Ferraz, Salvana Priscylla M. Costa, Tarcyla de A. Gomes, Giovanna Christinne R. M. Schver, Cristóvão R. da Silva, Magaly Andreza M. de Lyra, Danilo Augusto F. Fontes, Larissa A. Rolim, Amanda Carla Q. M. Vieira, Miracy M. de Albuquerque, Pedro J. Rolim-Neto

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Efavirenz (EFV) is a drug used as first-line treatment of AIDS. However, it has poor aqueous solubility and wettability, presenting problems in the gastrointestinal tract absorption and bioavailability. One of the most promising strategies to improve the solubility is the use of solid dispersions (SD). Therefore, this study aimed to characterize SD EFZ with the polymers: PVP-K30, PVPVA 64 and SOLUPLUS in order to find an optimal formulation to compose a future pharmaceutical product for AIDS therapy. Initially, Physical Mixtures (PM) and SD with the polymers were obtained containing 10, 20, 50 and 80% of drug (w/w) by the solvent method. The best formulation obtained between the SD was selected by in vitro dissolution test. Finally, the drug-carrier system chosen, in all ratios obtained, were analyzed by the following techniques: Differential Scanning Calorimetry (DSC), polarization microscopy, Scanning Electron Microscopy (SEM) and spectrophotometry of absorption in the region of infrared (IR). From the dissolution profiles of EFV, PM and SD, the values of area Under The Curve (AUC) were calculated. The data showed that the AUC of all PM is greater than the isolated EFV, this result is derived from the hydrophilic properties of the polymers thus favoring a decrease in surface tension between the drug and the dissolution medium. In adittion, this ensures an increasing of wettability of the drug. In parallel, it was found that SD whom had higher AUC values, were those who have the greatest amount of polymer (with only 10% drug). As the amount of drug increases, it was noticed that these results either decrease or are statistically similar. The AUC values of the SD using the three different polymers, followed this decreasing order: SD PVPVA 64-EFV 10% > SD PVP-K30-EFV 10% > SD Soluplus®-EFV 10%. The DSC curves of SD’s did not show the characteristic endothermic event of drug melt process, suggesting that the EFV was converted to its amorphous state. The analysis of polarized light microscopy showed significant birefringence of the PM’s, but this was not observed in films of SD’s, thus suggesting the conversion of the drug from the crystalline to the amorphous state. In electron micrographs of all PM, independently of the percentage of the drug, the crystal structure of EFV was clearly detectable. Moreover, electron micrographs of the SD with the two polymers in different ratios investigated, we observed the presence of particles with irregular size and morphology, also occurring an extensive change in the appearance of the polymer, not being possible to differentiate the two components. IR spectra of PM corresponds to the overlapping of polymer and EFV bands indicating thereby that there is no interaction between them, unlike the spectra of all SD that showed complete disappearance of the band related to the axial deformation of the NH group of EFV. Therefore, this study was able to obtain a suitable formulation to overcome the solubility limitations of the EFV, since SD PVPVA 64-EFZ 10% was chosen as the best system in delay crystallization of the prototype, reaching higher levels of super saturation.

Keywords: characterization, dissolution, Efavirenz, solid dispersions

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Authors: Ikram Elsiddig, Yacouba Djamila, Amna Hamad

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Abstract—The worldwide increasing of using herbs in form of medicine with or without prescription medications potentiates the interactions between herbal products and conventional medicines; due to more research for herb-drug interactions are needed. for a long time hyperglycemia had been treated with several medicinal plants. A. sativum, belonging to the Liliaceae family is well known for its medicinal uses in African traditional medicine, it used for treating of many human diseases mainly diabetes, high cholesterol and high blood pressure. The purpose of this study is to determine the interaction effect between A. sativum bulb extracts and metformin drug used in diabetes treatment. The in vitro and in vivo evaluation were conducted by glucose reuptake using isolated rats hemidiaphgrams tissue and by estimate glucose tolerance in glucose-loaded wistar albino rats. The results showed that, petroleum ether, chloroform and ethyl acetate extracts were found to have activity of glucose uptake in isolated rats hemidiaphgrams of 24.11 mg/g, 19.07 mg/g and 15.66 mg/g compared to metformin drug of 17 mg/g. These activity were reducded to 17.8 mg/g, 13.59 mg/g and 14.46 mg/g after combination with metformin, metformin itself reduced to 13.59 mg/g, 14.46 mg/g and 12.71 mg/g in comination with chloroform and ethyl acetate. These decrease in activity could be due to herbal–drug interaction between the extracts of A. sativum bulb and metformin drug. The interaction between A. sativum extract and metformin was also shown by in vivo study on the induced hyperglycemic rats. The glucose level after administered of 200 mg/kg was found to be increase with 47.2 % and 17.7% at first and second hour compared to the increase of blood glucose in the control group of 82.6% and76.7%.. At fourth hour the glucose level was became less than normal with 3.4% compared to control which continue to increase with 68.2%. Dose of 400 mg/kg at first hour showed increase in blood glucose of 31.5 %, at second and fourth hours the glucose level was became less than normal with decrease of 3.2 % and 30.4%. After combination the activity was found to be less than that of extract at both high and low dose, whereas, at first and second hour, the glucose level was found to be increase with 50.4% and 21.2%, at fourth hour the glucose level was became less than normal with 14%. Therefore A. sativum could be a potential source for anti-diabetic when it used alone, and it is significant important to use the garlic extract alone instead of combined with Metformin drug in diabetes- treatment.

Keywords: Antagonistic, Garlic, Metformin, Synergistic

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Authors: John Yahng, Hansraj Riteesh Bookun

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Popliteal artery aneurysms (PAAs) are the most common arterial aneurysm of the periphery. It is defined as focal dilation of the artery more than 50% of the normal vessel diameter which usually varies between 7 mm to 11 mm. The most common presentation for PAAs is claudication due to luminal stenosis secondary to mural thrombus or acute limb ischaemia due to occlusive thrombosis or distal thromboembolism. It is less common for patients to present with non-ischaemic symptoms secondary to mass effect and compression of adjacent structures, and of these, presentation with common peroneal nerve compression is particularly uncommon. We present a rare case of a 92-year-old female patient presenting with 4-month history of left foot drop with radiological evidence of common peroneal nerve compression secondary to PAA of 22 mm by 21mm in size. To the best of our knowledge, this is the smallest reported popliteal aneurysm presenting with foot drop. We also present the endovascular treatment option taken in our case.

Keywords: aneurysm, foot drop, peroneal nerve, popliteal

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Authors: Kairat Uteulin, Azhar Iskakova, Serik Mukhambetzhanov, Bayan Yesbolayeva, Gabit Bari, Aslan Zheksenbai, Kabyl Zhambakin, Chingis Dzhabykbayev, Vladimir Piven, Izbasar Rakhimbaiev

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To explore the potential for in vitro rapid regeneration of Russian dandelion (Taraxacum kok-saghyz Rodin), different concentrations of 6-Benzylaminopurine (BAP), 2,4-Dichlorophenoxyacetic acid (2.4-D) and BAP combined with Indole-3-acetic acid (IAA) were evaluated for their effects on the induction of somatic embryos from leaf, seed stem and root explants. Different explants were cultured on MS medium supplemented with various concentrations (0, 0.5, 1, 1.5, 2, 2.5 and 3 mg/l) of each kind of hormone. Callus induction percentage, fresh weight, color and texture of the callus were assessed after 14 and 28 days of culture. The optimum medium for the proliferation of embryogenic calli from leaf and root explants was MS supplemented with 2.5 mg/L BAP and 0.5 mg/L 2.4-D. Concentrations of 2.5 mg/L BAP and 1.5 mg/L IAA also had a remarkable effect on root and stem explants. The best concentration to produce callus from stem explants was 0.5 mg/L BAP and 1 mg/L IAA. Results of mean comparison showed that BAP and 2.4-D were more effective on different explants than BAP and IAA. Results of the double staining method proved that somatic embryogenesis occurred in the most concentrations of BAP and 2.4-D. Under microscopic observations, the different developmental stages of the embryos (globular, heart, torpedo and cotyledonary) were revealed together in callus cells, indicating that the most tested hormone combinations were effective for somatic embryogenesis formation in this species. Seed explants formed torpedo and cotyledonary stages faster than leaf and root explants in the most combinations. Most calli from seed explants were cream colored and friable, while calli were compact and light green from leaf and root explants. Some combinations gave direct regeneration and (3 mg/L BAP and 2 mg/L IAA) in seed explants and (0.5 mg/L BAP and 2.5 mg/L IAA) in leaf explants had the highest number of shoots with average of 21 and 27 shoots per callus. The developed protocol established the production of different callus types from seed, leaf, and root explants and plant regeneration through somatic embryogenesis.

Keywords: taraxacum kok-saghyz Rodin, callus, somatic embryogenesis

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Authors: Sunil Kumar

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For many years, small organic molecules derived naturally from microbes and plants have delivered a number of expedient therapeutic drug agents. The search for naturally occurring lead compounds has continued in recent years as well, with the constituents of marine flora and fauna along with those of telluric microorganisms and plants being investigated for their anti-bacterial and anti-cancer activities. It has been observed that such promising lead molecules incline to promptly generate substantial attention among scientists like synthetic organic chemists and biologists. Subsequently, the availability of a given precious natural product sample may be enriched, and it may be possible to determine a preliminary idea of structure-activity relationships to develop synthetic analogues. For instance, anti-tumor drug topotecan is a synthetic chemical compound similar in chemical structure to camptothecin which is found in extracts of Camptotheca acuminate. Similarly, researchers at AstraZeneca discovered anti-biotic pyrrolamide through a fragment-based lead generation approach from kibdelomycin, which is isolated from Staphylococcus aureuss.

Keywords: anticancer, antibiotic, lead molecule, natural product, synthetic analogues

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Authors: Natida Thongsima, Patompong Satapornpong

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Introduction: Lamotrigine is widely used in the treatment of epilepsy and bipolar disorder. However, lamotrigine leads to adverse drug reactions (ADRs) consist of severe cutaneous adverse reactions (SCARs) include Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug rash with eosinophilia and systemic symptoms (DRESS). Moreover, lamotrigine-induced SCARs are usually manifested between 2 and 8 weeks after treatment initiation. According to a previous study, the association between HLA-B*15:02 and lamotrigine-induced cutaneous adverse drug reactions in the Thai population (odds ratio 4.89; 95% CI 1.28–18.66; p-value = 0.014) was found. Therefore, the distribution of pharmacogenetics markers a major role in predicting the culprit drugs for SCARs in many populations. Objective: In this study, we want to investigate the prevalence of HLA-B allele, which correlates with lamotrigine-induced SCARs in the healthy Thai population. Materials and Methods: We enrolled 350 healthy Thai individuals and were approved by the ethics committee of Rangsit University. HLA-B alleles were genotyped by the Lifecodes HLA SSO typing kits (Immucor, West Avenue, Stamford, USA). Results: The results presented HLA-B allele frequency in healthy Thai population were 14.71% (HLA-B*46:01), 8.57% (HLA-B*15:02), 6.71% (HLA-B*40:01), 5.86% (HLA-B*13:01), 5.71% (HLA-B*58:01), 5.14% (HLA-B*38:02), 4.86% (HLA-B*18:01), 4.86% (HLA-B*51:01), 3.86% (HLA-B*44:03) and 2.71% (HLA-B*07:05). Especially, HLA-B*15:02 allele was the high frequency in the Thais (8.57%), Han Chinese (7.30%), Vietnamese (13.50%), Malaysian (6.06%) and Indonesian (11.60%). Nevertheless, this allele was much lower in other populations, namely, Africans, Caucasians, and Japanese. Conclusions: Although the sample size of the healthy Thai population in this research was limited, there were found the frequency of the HLA-B*15:02 allele could predispose them toward to lamotrigine-induced SCARs in Thailand.

Keywords: lamotrigine, cutaneous adverse drug reactions, HLA-B, Thai population

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Authors: Soad Ali Yehia, Mohamed Shafik El-Ridi, Mina Ibrahim Tadros, Nolwa Gamal El-Sherif

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Fexofenadine hydrochloride (FXD) is a slightly soluble, bitter-tasting, drug having an oral bioavailability of 35%. The maximum plasma concentration is reached 2.6 hours (Tmax) post-dose. The current work aimed to develop taste-masked FXD orodispersible tablets (ODTs) to increase extent of drug absorption and reduce Tmax. Taste masking was achieved via solid dispersion (SD) with chitosan (CS) or sodium alginate (ALG). FT-IR, DSC and XRD were performed to identify physicochemical interactions and FXD crystallinity. Taste-masked FXD-ODTs were developed via addition of superdisintegrants (crosscarmelose sodium or sodium starch glycolate, 5% and 10%, w/w) or sublimable agents (camphor, menthol or thymol; 10% and 20%, w/w) to FXD-SDs. ODTs were evaluated for weight variation, drug-content, friability, wetting time, disintegration time and drug release. Camphor-based (20%, w/w) FXD-ODT (F12) was optimized (F23) by incorporation of a more hydrophilic lubricant, sodium stearyl fumarate (Pruv®). The topography of the latter formula was examined via scanning electron microscopy (SEM). The in vivo estimation of FXD pharmacokinetics, relative to Allegra® tablets, was evaluated in healthy human volunteers. Based on the gustatory sensation test in healthy volunteers, FXD:CS (1:1) and FXD:ALG (1:0.5) SDs were selected. Taste-masked FXD-ODTs had appropriate physicochemical properties and showed short wetting and disintegration times. Drug release profiles of F23 and phenylalanine-containing Allegra® ODT were similar (f2 = 96) showing a complete release in two minutes. SEM micrographs revealed pores following camphor sublimation. Compared to Allegra® tablets, pharmacokinetic studies in healthy volunteers proved F23 ability to increase extent of FXD absorption (14%) and reduce Tmax to 1.83 h.

Keywords: fexofenadine hydrochloride, taste masking, chitosan, orodispersible

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Authors: Neslihan Demirci, Serdar Durdağı

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Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.

Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis

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Authors: Mahdi Akhbardeh

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St John's wort plant can help to treat depression disease through decreasing this disease symptom, due to having some similar features of Prozac (Fluoxetine Hcl) pill. People suffering from slight depression who have fear of using antidepressants side effects can use St John's wort drops under doctor observation. This method of treatment is proposed specially to those women who are spending menopause or depression resulted from this period. St John's wort plant have proposed traditional and plant medicine as newest researches in treating mood disorders compared to Prozac (Fluoxetine Hcl) drug in treating depression disease which is being administrated in clinic research center of Washington. Objective: the aim of this study is to find an alternative treatment method in people suffering from depression which are treated with Prozac (Fluoxetine Hcl). Almost 70 percent of treatment failures with Prozac (Fluoxetine Hcl) drug in patients suffering from slight to normal depression is due to intensive side effects including: decrease in blood pressure, reduce in sexual desire and 30 percent of it is due to this drug affectless in treatment procedure which leads to leaving treatment. Results of Hypercuim plant function are exactly similar to antidepressants. Increase in serotonin amount in brain synopsis terminal end causes increase in existence time of this material in this part. In fact these two drugs have similar function. Though side effects of Hypercuim plant(St John's wort) including headache and slight nausea tolerable. Results: St John's wort plant can be used lonely in slight to normal depressions in which patients are avoiding Prozac (Fluoxetine Hcl) drug due to it's side effects. In intensive depressions through which general patients don’t indicate positive response to drug, it is probably expected relative or even complete treatment through combining antidepressants drugs with this plant. This treatment method has been investigated and confirmed in clinical tests and researches.

Keywords: depression, St John's wort, Prozac, antidepressant

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Authors: Michelle V. Tomczak, Reyhaneh Bakhtiari, Aaron Granley, Anthony Singhal

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Objective: Cannabis and cocaine are associated with a range of mental and physical effects that can impair aspects of human behavior. Driving is a complex cognitive behavior that is an essential part of everyday life and can be broken down into many subcomponents, each of which can uniquely impact road safety. With the growing movement of jurisdictions to legalize cannabis, there is an increased focus on impairment and driving. The purpose of this study was to identify driving-related cognitive-performance deficits that are impacted by recreational drug use. Design and Methods: With the assistance of law enforcement agencies, we recruited over 300 participants under the influence of various drugs including cannabis and cocaine. These individuals performed a battery of computer-based tasks scientifically proven to be re-lated to on-road driving performance and designed to test response-speed, memory processes, perceptual-motor skills, and decision making. Data from a control group with healthy non-drug using adults was collected as well. Results: Compared to controls, the drug group showed def-icits in all tasks. The data also showed clear differences between the cannabis and cocaine groups where cannabis users were faster, and performed better on some aspects of the decision-making and perceptual-motor tasks. Memory performance was better in the cocaine group for simple tasks but not more complex tasks. Finally, the participants who consumed both drugs performed most similarly to the cannabis group. Conclusions: Our results show distinct and combined effects of cannabis and cocaine on human performance relating to driving. These dif-ferential effects are likely related to the unique effects of each drug on the human brain and how they distinctly contribute to mental states. Our results have important implications for road safety associated with driver impairment.

Keywords: driving, cognitive impairment, recreational drug use, cannabis and cocaine

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Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Rosa L. Figueroa, Joselyn A. Hernández

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During the last couple of years, the Ministry of Health have been developing new health policies in order to regulate and improve in benefit of the patient the pharmaceutical system in our country. However, there are still some deficiencies in how medicines have been accessed, distributed, and sold. Therefore, it is necessary to empower the patient by offering new instances to improve access to drug information. This work introduces ‘the bioequivalent’ a medical drug search tool created to increase both diffusion and getting information about the therapeutic equivalence of medicines for the patient. The development of the search tool started with a study on the availability of sources of drug information accessible to the patient where advantages and disadvantages were analyzed. The information obtained was used to feed the functional design of the new tool. The design of the new tool shows an external interface that includes a header, body, sidebar and footer. The header has a menu containing ‘Home,’ ‘Who we are,’ and ‘Mission and vision.’ The Body contains the medical drug search tool, and the Sidebar is for the user logging in. It could be anonym, registered user, as well as, administrator. Anonym user could only use the tool. Registered users could add some information on existing medicines in the database; however, adding information will be restricted and limited to specific items and subject to administrator approval because the information added must be endorsed by the Chilean Public Health Institute. On the other hand, the administrator will have all the privileges, including creating or deleting drugs or information about them. The Bioequivalent was tested on different mobile devices, and no fails have been found. Moreover, a small survey was answered by ten people who tested the tool, and all of them agree that the tool was useful to get information about bioequivalent drugs, and they would recommend the tool to others. Nevertheless, an 80% of people who tested the tool says it was easy to use, and a 70% indicates that additional help is not required. These results are evidence that ‘the Bioequivalent’ may contribute to the knowledge about the therapeutic bioequivalence and bioequivalent drugs existing in Chile. As future work, the tool will be developed to make it available to the public for a first testing stage in a more massive scenario.

Keywords: collaborative database, bioequivalent drugs, search tool, web platform

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Authors: Olga Długosz, Jolanta Pulit-Prociak, Marcin Banach

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The paper presents a process to obtain glutathione-modified titanium oxide nanoparticles. The processes were carried out in a microwave radiation field. The influence of the molar ratio of glutathione to titanium oxide and the effect of the fold of NaOH vs. stoichiometric amount on the size of the formed TiO₂ nanoparticles was determined. The physicochemical properties of the obtained products were evaluated using dynamic light scattering (DLS), transmission electron microscope- energy-dispersive X-ray spectroscopy (TEM-EDS), low-temperature nitrogen adsorption method (BET), X-Ray Diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) microscopy methods. The size of TiO₂ nanoparticles was characterized from 30 to 336 nm. The release of titanium ions from the prepared products was evaluated. These studies were carried out using different media in which the powders were incubated for a specific time. These were water, SBF and Ringer's solution. The release of titanium ions from modified products is weaker compared to unmodified titanium oxide nanoparticles. The reduced release of titanium ions may allow the use of such modified materials as substances in drug delivery systems.

Keywords: titanium dioxide, nanoparticles, drug carrier, glutathione

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Authors: Olga Długosz, Jolanta Pulit-Prociak, Marcin Banach

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The paper presents a process to obtain glutathione-modified titanium oxide nanoparticles. The processes were carried out in a microwave radiation field. The influence of the molar ratio of glutathione to titanium oxide and the effect of the fold of NaOH vs. stoichiometric amount on the size of the formed TiO₂ nanoparticles was determined. The physicochemical properties of the obtained products were evaluated using dynamic light scattering (DLS), transmission electron microscope- energy-dispersive X-ray spectroscopy (TEM-EDS), low-temperature nitrogen adsorption method (BET), X-Ray Diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) microscopy methods. The size of TiO₂ nanoparticles was characterized from 30 to 336 nm. The release of titanium ions from the prepared products was evaluated. These studies were carried out using different media in which the powders were incubated for a specific time. These were: water, SBF, and Ringer's solution. The release of titanium ions from modified products is weaker compared to unmodified titanium oxide nanoparticles. The reduced release of titanium ions may allow the use of such modified materials as substances in drug delivery systems.

Keywords: titanium dioxide, nanoparticles, drug carrier, glutathione

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Authors: Tomáš Nejedlý, Dominika Mrázková, Jitka Viktorová

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The blood-brain barrier (BBB) serves as a protective shield, preventing the entry of harmful substances into the central nervous system. On the other hand, it also restricts the transport of neuroactive drugs, such as antiepileptics, which mitigate epileptic seizures. Drug-resistant epilepsy is often associated with the overexpression of efflux transporters, including P-glycoprotein (P-gp) or multidrug resistance protein 1 (MRP1), on the BBB. The aim of this work is to find P-gp and MRP1 inhibitors derived from phytocannabinoids and terpenes. The work evaluates whether these compounds interact directly with P-gp or MRP1 by rhodamine 123 or fluorescein efflux assay. The effect of phytocannabinoids on the gene expression of these transporters is also studied using qPCR and Western blot. These transporters are found in BBB cells; however, we decided to use the human ovarian cancer cell line (A2780ADR) due to its overproduction of P-gp and malignant glioma cell line (U87) due to its overproduction of MRP1. The results showed that while terpenes suppressed the activity of efflux transporters, phytocannabinoids tended to decrease their expression. Terpenes demonstrated an average inhibition of 65%, surpassing phytocannabinoids, which exhibited an average inhibition of approximately 30%. Particularly noteworthy was the modulating effect of (-)-α-bisabolol with the highest activity among the compounds tested. Based on these findings, phytocannabinoids and terpenes emerge as promising natural candidates for addressing drug resistance linked to efflux transporters. Acknowledgment: The project was funded by the Grant No 22-20860S of The Czech Science Foundation.

Keywords: drug-resistant epilepsy, efflux transporters, multidrug resistance protein 1, P-glycoprotein, phytocannabinoids, terpens

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Authors: Kyou Hee Shim, Hwa Sung Shin

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When a thrombolysis agent is administered to treat ischemic stroke, excessive reactive oxygen species are generated due to a sudden provision of oxygen and occurs secondary damage cell necrosis. Thus, it is necessary to administrate adjuvant as well as thrombolysis agent to protect and reduce damaged tissue. As cerebral blood vessels have specific structure called blood-brain barrier (BBB), it is not easy to transfer substances from blood to tissue. Therefore, development of a drug carrier is required to increase drug delivery efficiency to brain tissue. In this study, cyanobacterial pigment from the blue-green algae known for having neuroprotective effect as well as antioxidant effect was nasally administrated for bypassing BBB. In order to deliver cyanobacterial pigment efficiently, the nano-sized liposome was used as a carrier. Liposomes were coated with a positive charge of chitosan since negative residues are present at the nasal mucosa the first gateway of nasal administration. Characteristics of liposome including morphology, size and zeta potential were analyzed by transmission electron microscope (TEM) and zeta analyzer. As a result of cytotoxic test, the liposomes were not harmful. Also, being administered a drug to the ischemic stroke animal model, we could confirm that the pharmacological effect of the pigment delivered by chitosan coated liposome was enhanced compared to that of non-coated liposome. Consequently, chitosan coated liposome could be considered as an optimized drug delivery system for the treatment of acute ischemic stroke.

Keywords: ischemic stroke, cyanobacterial pigment, liposome, chitosan, nasal administration

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Authors: David Armany, Matthew Allaway, Preet Gosal, Senarath Edirimanne

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A potentially devastating complication of routine laparoscopic cholecystectomy includes iatrogenic bile duct injuries, which represent a stable incidence rate of 0.3% over the past three decades. Whilst related to several relative risks such as surgeon experience and patient factors (older age, male sex), misinterpretation of biliary tree anatomy remains the most common cause, accounting for 80% of iatrogenic Common Bile Duct injuries. Whilst extremely rare, a duplicate common bile duct anomaly remains a potential variation to encounter during biliary surgery, with 30 recognised cases in the worldwide literature, of which type Vb accounts for 4. We report the case of a rare type Vb variation encountered during intra-operative laparoscopic cholecystectomy and confirmed on cholangiogram. To our knowledge, this is the first documented Type Vb case encountered in an Australian population. Given these anomalies are asymptomatic and can perpetuate iatrogenic common bile duct injuries, awareness of all subtypes is crucial. Irrevocably, preoperative Magnetic Resonance Cholangiopancreatography can help recognise these anomalies before the operating theatre; however, their widespread adoption is limited by expensive and availability.

Keywords: duplicated common bile duct, type Vb, cholecystitis, MRCP, cholangiogram, iatrogenic CBD

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

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Authors: Bouami Hind, Millot Patrick

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The implementation of automated devices in life-critical systems such as hospitals can bring a new set of challenges related to automation malfunctions. While automation has been identified as great leverage for the medication dispensing system’s security and efficiency, it also increases the complexity of the organization. In particular, the installation and operation stage of automated devices can be complex when malfunctions related to automated systems occur. This paper aims to document operators’ situation awareness about the malfunctions of automated drug delivery systems (ADCs) during their implementation through Saint Brieuc hospital’s feedback. Our evaluation approach has been deployed in Saint Brieuc hospital center’s pharmacy, which has been equipped with automated nominative drug dispensing systems since January of 2021. The analysis of Saint Brieuc hospital center pharmacy’s automation revealed numerous malfunctions related to the implementation of Automated Delivery Cabinets. It appears that the targeted performance is not reached in the first year of implementation in this case study. Also, errors have been collected in patients' automated treatments’ production such as lack of drugs in pill boxes or nominative carnets, excess of drugs, wrong location of the drug, drug blister damaged, non-compliant sachet, or ticket errors. Saint Brieuc hospital center’s pharmacy is doing a tremendous job of setting up and monitoring performance indicators from the beginning of automation and throughout ADC’s operation to control ADC’s malfunctions and meet the performance targeted by the hospital. Health professionals, including pharmacists, biomedical engineers and directors of work, technical services and safety, are heavily involved in an automation project. This study highlights the importance of the evaluation of ADCs’ performance throughout the implementation process and the hospital’s team involvement in automation supervision and management.

Keywords: life-critical systems, situation awareness, automated delivery cabinets, implementation, risks and malfunctions

Procedia PDF Downloads 78

Authors: Ali Ayatic, Emad Mozaffari, Bahareh Tanhaei, Maryam Khajenoori, Saeedeh Movaghar Khoshkho, Ali Ayati

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The abuse of antibiotics, such as tetracycline (TC), is a great global threat to people and the use of topical antibiotics is a promising tact that can help to solve this problem. Antibiotic therapy is often appropriate and necessary for acute wound infections, while topical tetracycline can be highly efficient in improving the wound healing process in diabetics. Due to the advantages of drug-loaded hydrogels as wound dressing, such as ease of handling, high moisture resistance, excellent biocompatibility, and the ability to activate immune cells to speed wound healing, it was found as an ideal wound treatment. In this work, the tetracycline-loaded hydrogels combining agar (AG) and κ-carrageenan (k-CAR) as polymer materials were prepared, in which span60 surfactant was introduced inside as a drug carrier. The Field Emission Scanning Electron Microscopes (FESEM) and Fourier-transform infrared spectroscopy (FTIR) techniques were employed to provide detailed information on the morphology, composition, and structure of fabricated drug-loaded hydrogels and their mechanical properties, and hydrogel permeability to water vapor was investigated as well. Two types of gram-negative and gram-positive bacteria were used to explore the antibacterial properties of prepared tetracycline-contained hydrogels. Their swelling and drug release behavior was studied using the changing factors such as the ratio of polysaccharides (MAG/MCAR), the span60 surfactant concentration, potassium chloride (KCl) concentration and different release media (deionized water (DW), phosphate-buffered saline (PBS), and simulated wound fluid (SWF)) at different times. Finally, the kinetic behavior of hydrogel swelling was studied. Also, the experimental data of TC release to DW, PBS, and SWF using various mathematical models such as Higuchi, Korsmeyer-Peppas, zero-order, and first-order in the linear and nonlinear modes were evaluated.

Keywords: drug release, hydrogel, tetracycline, wound healing

Procedia PDF Downloads 64

Authors: Lebogang Jane Msiza, Felix Dapare Dakora

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Photosynthesis is a process by which plants convert light energy to chemical energy for metabolic processes. Plants are known for converting inorganic CO₂ in the atmosphere to organic C by photosynthesis. A decrease in stomatal conductance causes a decrease in the transpiration rate of leaves, thus increasing the water-use efficiency of plants. Water-use efficiency in plants is conditioned by soil moisture availability and is enhanced under conditions of water deficit. This study evaluated leaf photosynthesis and water-use efficiency in 12 legume species inoculated with 26 rhizobial isolates from soybean, 15 from common bean, 10 from cowpea, 15 from Bambara groundnut, 7 from lessertia and 10 from Kersting bean. Gas-exchange studies were used to measure photosynthesis and water-use efficiency. The results revealed a much higher photosynthetic rate (20.95µmol CO₂ m-2s-1) induced by isolated tutpres to a lower rate (7.06 µmol CO₂ m-2s-1) by isolate mgsa 88. Stomatal conductance ranged from to 0.01 mmol m-2.s-1 by mgsa 88 to 0.12 mmol m-2.s-1 by isolate da-pua 128. Transpiration rate also ranged from 0.09 mmol m-2.s-1 induced by da-pua B2 to 3.28 mmol m-2.s-1 by da-pua 3, while water-use efficiency ranged from 91.32 µmol CO₂ m-1 H₂O elicited by mgsa 106 to 4655.50 µmol CO₂ m-1 H₂O by isolate tutswz 13. The results revealed the highest photosynthetic rate in soybean and the lowest in common bean, and also with higher stomatal conductance and transpiration rates in jack bean and Bambara groundnut. Pigeonpea exhibited much higher water-use efficiency than all the tested legumes. The findings showed significant differences between and among the test legume/rhizobia combinations. Leaf photosynthetic rates are reported to be higher in legumes with high stomatal conductance, which suggests that legume productivity can be improved by manipulating leaf stomatal conductance.

Keywords: legumes, photosynthetic rate, stomatal conductance, water-use efficiency

Procedia PDF Downloads 204

Authors: H. Aksas, S. Boughrara, K. Louhab

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The goal of this study was the use of life cycle assessment (LCA) methodology to assess the environmental impact of pharmaceutical product (four kinds of syrup form and tree kinds of pomade form), which are produced in one leader manufactory in Algeria town that is SAIDAL Company. The impacts generated have evaluated using SimpaPro7.1 with CML92 Method for syrup form and EPD 2007 for pomade form. All impacts evaluated have compared between them, with determination of the compound contributing to each impacts in each case. Data needed to conduct Life Cycle Inventory (LCI) came from this factory, by the collection of theoretical data near the responsible technicians and engineers of the company, the practical data are resulting from the assay of pharmaceutical liquid, obtained at the laboratories of the university. This data represent different raw material imported from European and Asian country necessarily to formulate the drug. Energy used is coming from Algerian resource for the input. Outputs are the result of effluent analysis of this factory with different form (liquid, solid and gas form). All this data (input and output) represent the ecobalance.

Keywords: pharmaceutical product, drug residues, LCA methodology, environmental impacts

Procedia PDF Downloads 229

Authors: Manaphol Kulpraneet, Anirut Limtrakul, Surangrat Srisurapanon, Piyatida Tangteerawatana

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Tuberculosis (TB) remains a global health care disease world-wide. Control of the global TB epidemic has been impaired by the lack of an effective vaccine, by the emergence of drug resistant forms of Mycobacterium tuberculosis and by lack of sensitive and rapid diagnostics. Cytokines play a major role in defense against M. tuberculosis infection. Polymorphisms in the genes encoding various cytokines have been associated with tuberculosis susceptibility. Polymorphisms of the regulatory cytokine gene, the interleukin (IL)-10 is associated with the risk of tuberculosis (TB) in different populations. However, IL-10 gene polymorphism and susceptibility to TB in Thai is still unknown. The purpose of this study was to evaluate whether the common IL-10 promoter gene polymorphisms are associated with TB in Thai population. Forty eight patients with newly diagnosed pulmonary tuberculosis were studied. DNA samples were extracted from leukocytes and used to investigate -1087A/G, -819C/T, -252C/A (rs1800896, rs1800871, rs1800872) in IL-10 gene using restriction fragment length polymorphism (PCR-RFLP) methods. In this study, the genotype and allele frequencies of IL-10-1087A/G, -819C/T, -252C/A polymorphism did not significantly different between TB patients and healthy controls ((genotype: p=0.38, p=0.92, p=1; allele: p=0.57, p=0.77, p=0.89, respectively). The lack of association between common IL-10 promoter polymorphisms and TB susceptibility in this study may provide clue for better understanding of IL-10-1087A/G, -819C/T, -252C/A polymorphism and TB susceptibility in Thai population, which might facilitate the rationale design of vaccines. However, further studies in large scales population are required for confirmation.

Keywords: IL-10, cytokines, single nucleotide polymorphism (SNP), tuberculosis

Procedia PDF Downloads 310

Authors: Mewa Singh

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Nanomedicine, a fusion of nanotechnology and medicine, is an emerging technology ideally suited to the targeted therapies. Nanoparticles overcome the low selectivity of anti-cancer drugs toward the tumor as compared to normal tissue and hence result-in less severe side-effects. Our new technology, HYBRID-NANOENGINEERING™, uses a new molecule (MR007) in the creation of nanoparticles that not only helps in nanonizing the medicine but also provides synergy to the medicine. The simplified manufacturing process will result in reduced manufacturing costs. Treatment is made more convenient because hybrid nanomedicines can be produced in oral, injectable or transdermal formulations. The manufacturing process uses no protein, oil or detergents. The particle size is below 180 nm with a narrow distribution of size. Importantly, these properties confer great stability of the structure. The formulation does not aggregate in plasma and is stable over a wide range of pH. The final hybrid formulation is stable for at least 18 months as a powder. More than 97 drugs, including paclitaxel, docetaxel, tamoxifen, doxorubicinm prednisone, and artemisinin have been nanonized in water soluble formulations. Preclinical studies on cell cultures of tumors show promising results. Our HYBRID-NANOENGINEERING™ platform enables the design and development of hybrid nano-pharmaceuticals that combine efficacy with tolerability, giving patients hope for both extended overall survival and improved quality of life. This study would discuss or present this new discovery of HYBRID-NANOENGINEERING™ which targets drug delivery, synergistic, and potentiating effects, and barriers of drug delivery and advanced drug delivery systems.

Keywords: nano-medicine, nano-particles, drug delivery system, pharmaceuticals

Procedia PDF Downloads 468

Authors: S. T. Kumbhar, M. S. Bhatia, R. C. Khairate

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An effective nanodrug delivery system was developed by using chitosan for increased encapsulation efficiency and retarded release of curcumin. Potential ionotropic gelation method was used for the development of chitosan nanoparticles with TPP as cross-linker. The characterization was done for analysis of size, structure, surface morphology, and thermal behavior of synthesized chitosan nanoparticles. The encapsulation efficiency was more than 80%, with improved drug loading capacity. The in-vitro drug release study showed that curcumin release rate was decreased significantly. These chitosan nanoparticles could be a suitable platform for co-delivery of curcumin and anticancer agent for enhanced cytotoxic effect on tumor cells.

Keywords: Curcumin, chitosan, nanoparticles, anticancer activity

Procedia PDF Downloads 154

Authors: Jamil Jafari, Sharafat Karimi

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The Arabic Language has a complicated system of prosody invented by the great grammarian Khalil Ibn Ahmad Farahidi. He could extract 15 meters out of his innovative five circles, which were used in Arabic poetry of the 7th and 8th centuries. Then after a while, his student Akhfash added or compensated another meter to his tutor's meters, so overall, we now have 16 different meters in Arabic poetry. These meters have been formed by various combinations of 8 different feet and each foot is combined of rudimentary units called Sabab and Wated which are combinations of movement (/) and silent (ʘ) letters. On the other hand in English, we are dealing with another system of metrical prosody. In this language, feet are consisted of stressed and unstressed syllables and are of six types: iamb, trochee, dactyl, anapest, spondee, and pyrrhic. Using the descriptive-analytic method, in this research we aim at making a comparison between Arabic and English systems of metrical prosody to investigate their similarities and differences. The results show that both of them are quantitative and both of them rely on syllables in afoot. But unlike Arabic, English is utilizing another rhyme system and the number of feet in a line differs from Arabic; also, its feet are combined of stressed and unstressed syllables, while those of Arabic is a combination of movement and silent letters.

Keywords: Arabic prosody, English prosody, foot, meter, poetry

Procedia PDF Downloads 128

Authors: Daria Zabolotnaya, Svetlana Degtyareva, Veronika Kanestri, Danila Konnov

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An adequate choice of the initial antiretroviral treatment determines the treatment efficacy. In the clinical guidelines in Russia non-nucleoside reverse transcriptase inhibitors (NNRTIs) are still considered to be an option for first-line treatment while pretreatment drug resistance (PDR) testing is not routinely performed. We conducted a cohort retrospective study in HIV-positive treatment naïve patients of the H-clinic (Moscow, Russia) who performed PDR testing from July 2017 to November 2021. All the information was obtained from the medical records anonymously. We analyzed the mutations in reverse transcriptase and protease genes. RT-sequences were obtained by AmpliSens HIV-Resist-Seq kit. Drug resistance was defined using the HIVdb Program v. 8.9-1. PDR was estimated using the Stanford algorithm. Descriptive statistics were performed in Excel (Microsoft Office, 2019). A total of 261 HIV-1 infected patients were enrolled in the study including 197 (75.5%) male and 64 (24.5%) female. The mean age was 34.6±8.3 years. The median CD4 count – 521 cells/µl (IQR 367-687 cells/µl). Data on risk factors of HIV-infection were scarce. The total quantity of strains containing mutations in the reverse transcriptase gene was 75 (28.7%). From these 5 (1.9%) mutations were associated with PDR to nucleoside reverse transcriptase inhibitors (NRTIs) and 30 (11.5%) – with PDR to NNRTIs. The number of strains with mutations in protease gene was 43 (16.5%), from these only 3 (1.1%) mutations were associated with resistance to protease inhibitors. For NNRTIs the most prevalent PDR mutations were E138A, V106I. Most of the HIV variants exhibited a single PDR mutation, 2 were found in 3 samples. Most of HIV variants with PDR mutation displayed a single drug class resistance mutation. 2/37 (5.4%) strains had both NRTIs and NNRTIs mutations. There were no strains identified with PDR mutations to all three drug classes. Though earlier data demonstrated a lower level of PDR in HIV treatment naïve population in Russia and our cohort can be not fully representative as it is taken from the private clinic, it reflects the trend of increasing PDR especially to NNRTIs. Therefore, we consider either pretreatment testing or giving the priority to other drugs as first-line treatment necessary.

Keywords: HIV, resistance, mutations, treatment

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