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Preprint CASE REPORT | doi:10.20944/preprints202303.0402.v1

Thrombosis of Transverse Cerebral Venous Sinus Secondary to Vaccine ChAdOx1-S (Recombinant) First Report in Southamerica

Luis Dulcey, Juan Theran, Edgar Blanco, Maria Paula Ciliberti, Laura Nathalia Gutierrez, Catalina Herran Fonseca, Juan Martinez

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Vaccine; Coronavirus; Thrombosis; Brain

Online: 22 March 2023 (14:50:00 CET)

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Preprint REVIEW | doi:10.20944/preprints202303.0344.v1

Strategies for the Management of Spike Protein-Related Pathology

Matthew T.J. Halma, Cristof Plothe, Theresa Lawrie

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Long Covid; Covid-19 vaccine; thrombosis; clots; inflammation; therapeutics

Online: 20 March 2023 (04:37:02 CET)

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Preprint ARTICLE | doi:10.20944/preprints202303.0343.v1

A pilot Study to Assess Prescription Transfer and Medicines Collection through a New Electronic Prescription Service: A Cross-Sectional Survey

Mansour Tobaiqy, Bayan E Ainousah, Nasser M Alorfi, Alaa Alghamdi, Sulafa Tarek Alqutub

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Wasfaty Service; e-Prescription Transfer; Medicines Collection; Questionnaire

Online: 20 March 2023 (04:32:49 CET)

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Preprint REVIEW | doi:10.20944/preprints202211.0221.v3

Tucaresol: A Unique Oral Candidate Drug Ideally Accessible for Treatment of COVID-19 Disease

Christopher Penney, Boulos Zacharie, Jean-Simon Duceppe

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Tucaresol; COVID-19; SARS-CoV-2; HIV; T helper cell; CD4 receptor

Online: 14 March 2023 (08:51:05 CET)

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Abstract: The SARS-CoV-2 pandemic has significantly impacted world health and economic status. In response, much work has been undertaken to provide effective, safe vaccines, antibodies and antiviral drugs with which to address this pandemic. Treatment of a pandemic population presents multiple challenges in addition to the primary issue of drug efficacy and safety, such as large scale drug manufacture and distribution, drug stability, oral dosing and pharmacoeconomic considerations. Ideally, these factors must be addressed if new candidate drugs are to be advanced for treatment of large (pandemic) populations. Subsequently, new antivirals have reached the market but choices are few. According to the NIH Covid Treatment Guidelines, only three small molecule antiviral drugs are available to treat COVID-19 disease. As such, a significant part of the research towards discovery of new antiviral drugs has focused on screening and evaluation of ‘repurposed drugs’ or previously approved or clinical stage drugs. Yet, in spite of this increased research activity, one promising clinical stage candidate drug has received little attention regarding its potential as a monotherapy or component of combination therapy for treatment of COVID-19 disease. Tucaresol, with documented human safety and pharmacokinetic data, is an orally active, stable, small molecule amenable to large scale manufacture by a proprietary two-step synthesis developed by us. Tucaresol functions as a host-targeted antiviral by selective protection/reconstitution of CD4+ T helper cells as demonstrated in HIV patients and SIV macaques. In view of similarities between HIV and SARS-CoV-2, especially with respect to host CD4+ T helper cells, and the suitability of Tucaresol for facile treatment of pandemic populations, Tucaresol is presented herein for treatment of mild-to-moderate COVID-19 patients but may also be useful for treatment of advanced disease accompanied by lymphopenia.

Preprint ARTICLE | doi:10.20944/preprints202303.0231.v1

Antidotal Effect of Dihydroxyacetone in Aluminum Phosphide-Intoxicated Patients

Reza Heidari, Hossein Niknahad, Ali Jangjoo, Vahidreza Asghari

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Aluminum phosphide; Clinical Toxicology; Dihydroxyacetone; Pharmacotherapy; Phosphine; Suicide; Toxicity

Online: 13 March 2023 (10:37:23 CET)

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Background: Aluminum phosphide (AlP), also known as “rice tablet,” is widely used as an effective pesticide. However, AlP poisoning is a common cause of mortality in many countries, such as Iran. Unfortunately, there is no specific antidote for AlP toxicity to date. AlP releases phosphine gas when it is exposed to moisture and acid. Phosphine is a robust mitochondrial toxin that could significantly inhibit cellular energy metabolism. AlP poisoning is an emergency condition that needs instant and effective intervention. Dihydroxyacetone (DHA) is a simple saccharide used for several pharmacological as well as cosmetic purposes. Previously, we found that DHA could significantly prevent mitochondrial impairment induced by toxic agents such as cyanide and phosphine in various in vitro and in vivo experimental models.Methods: Hospitalized patients (n = 111) were evaluated for eligibility criteria. Among these patients, n = 35 cases were excluded due to incomplete data (n = 11) and suspicion of poisoning rather than AlP (n = 24). Meanwhile, n = 76 cases with confirmed AlP poisoning were included in the study. AlP-poisoned patients who did not receive DHA (n =18) were used as the control group.Patients (n = 58) received at least one dose of DHA (500 ml of 5% DHA solution w/v, i.v.) in addition to routine treatment of AlP poisoning. Arterial blood gas (ABG), blood pH, bicarbonate levels, and other vital signs and biochemical measurements were monitored. Moreover, the mortality rate and time of hospitalization were evaluated in both DHA-treated (n = 58) and AlP-poisoned patients without DHA administration (n = 18). Several biomarkers were assessed before (upon hospitalization) and after DHA treatment. The routine tests for AlP-poisoned patients in this study were the measurement of electrolytes (K+ and Na+), WBC, RBC, hemoglobin, INR, carbonate (HCO3), blood pH, PaCO2, and PaO2 and SGPT, SGOT, BUN, Cr. Results: Upon patients' admission, significant decreases in blood pH (acidosis), blood PaO₂, and HCO₃ levels were the hallmarks of AlP poisoning. It was found that DHA significantly alleviated biomarkers of AlP poisoning and tremendously enhanced patients’ survival rate compared to patients treated based on hospital routine AlP poisoning protocols (no DHA). No significant adverse effects were evident in DHA-treated patients in the current study.Interpretation: These data suggest that parenteral DHA is a novel and effective antidote against AlP poisoning.Trial registration: IR.SUMS.REC.1394.102

Preprint ARTICLE | doi:10.20944/preprints202303.0193.v1

Complex Networks Analyses of Antibiofilm Peptides: An Emerging Tool for Next Generation Antimicrobials Discovery

Guillermin Agüero-Chapin, Agostinho Antunes, José R. Mora, Noel Pérez, Ernesto Contreras‑Torres, José R. Valdes-Martini, Felix Martinez-Rios, Cesar H. Zambrano, Yovani Marrero-Ponce

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Antibiofilm peptide; chemical space; StarPep toolbox; complex network; centrality measure; motif discovery

Online: 10 March 2023 (09:36:30 CET)

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Preprint ARTICLE | doi:10.20944/preprints202303.0151.v1

Trichoderma asperellum Extract Isolated From Brazil Nuts (Bertholletia excelsa. BONPL): In Vivo and In Silico Studies on Melanogenesis in Zebrafish

Adriana Maciel Ferreira, Iracirema da Silva Sena, Jhone Curti, Agerdânio Andrade De Souza, Paulo Cesar dos Santos Lima, Alex Bruno Lobato Rodrigues, Ryan da Silva Ramos, Wandson Braamcamp de Souza Pinheiro, Irlon Maciel Ferreira, José Carlos Tavares Carvalho

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Amazon fungi; Fungus extract; Trichoderma asperellum; Melanogenesis; Zebrafish

Online: 8 March 2023 (08:48:58 CET)

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Preprint REVIEW | doi:10.20944/preprints202302.0510.v1

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

Yan Yik Lim, Ahmad Mujahid Ahmad Zaidi, Azizi Miskon

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Metal-Based Drugs; CuZn; Anti-Chemoresistance; Osteosarcoma Therapy; Ligand Biosensors.

Online: 28 February 2023 (06:51:00 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0447.v1

Urinary Excretion Kinetics of Salbutamol and Its Sulfoconjugated Main Metabolite After Oral and Inhalative Administration of Racemic Salbutamol or Levosalbutamol

Annika Lisa Jendretzki, Lukas Corbinian Harps, Yanan Sun, Felix Bredendiek, Matthias Bureik, Ulrich Girreser, Xavier De la Torre, Francesco Botrè, Maria Kristina Parr

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: salbutamol; metabolism; excretion rates; salbutamol-4’-O-sulfate; bioanalysis; biosynthesis; SULT1A3

Online: 27 February 2023 (06:27:43 CET)

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Preprint REVIEW | doi:10.20944/preprints202302.0173.v1

Proposing Intranasal Rifampin for Alzheimer’s Disease and the Other Age-Related Neurodegenerative Proteinopathies

Coad Thomas Dow, Laith Kidess

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: ifampin; proteinopathies; permeability glycoprotein; intranasal; bi-directional; Alzheimer’s; Parkinson’s; Lewy body dementia; multiple system atrophy; huntington’s; amyotrophic lateral sclerosis/frontotemporal dementia spectrum

Online: 10 February 2023 (02:31:56 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0152.v1

Frontline Sodium Channel-Blocking Antiseizure Medicine Use Promotes Future Onset of Drug-Resistant Chronic Seizures

Dannielle Zierath, Stephanie Mizuno, Melissa Barker-Haliski

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: carbamazepine; levetiracetam; gabapentin; perampanel; valproic acid; phenobarbital; topiramate; neurogenesis; Ki-67

Online: 9 February 2023 (03:00:09 CET)

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The mechanisms of treatment-resistant epilepsy remain unclear. We have previously shown that frontline administration of therapeutic doses of lamotrigine (LTG), which preferentially inhibits the fast-inactivation state of sodium channels, during corneal kindling of mice promotes cross-resistance to several other antiseizure medicines (ASMs). However, whether this phenomenon extends to monotherapy with ASMs that stabilize the slow inactivation state of sodium channels is unknown. Therefore, this study assessed whether lacosamide (LCM) monotherapy during corneal kindling would promote future development of drug-resistant focal seizures in mice. Male CF-1 mice (n=40/group; 18-25 g) were administered an anticonvulsant dose of LCM (4.5 mg/kg, ip), LTG (8.5 mg/kg, ip), or vehicle (0.5% methylcellulose) twice daily for two weeks during kindling. A subset of mice (n=10/group) were euthanized 1 day after kindling for immunohistochemical assessment of astrogliosis, neurogenesis, and neuropathology. The dose-related antiseizure efficacy of distinct ASMs, LTG, LCM, carbamazepine, levetiracetam, gabapentin, perampanel, valproic acid, phenobarbital, and topiramate was then assessed in remaining kindled mice. Neither LCM nor LTG administration prevented kindling: 29/39 vehicle-exposed mice were kindled; 33/40 LTG-exposed mice were kindled; and 31/40 LCM-exposed mice were kindled. Mice administered LCM or LTG during kindling became resistant to escalating doses of LCM, LTG, and carbamazepine. Perampanel, valproic acid, and phenobarbital were less potent in LTG- and LCM-kindled mice, whereas levetiracetam and gabapentin retained equivalent potency across groups. Notable differences in reactive gliosis and neurogenesis were also appreciated. This study indicates that early, repeated administration of sodium channel blocking ASMs, regardless of inactivation state preference, promotes pharmacoresistant chronic seizures. Inappropriate ASM monotherapy in newly diagnosed epilepsy may thus be one driver of future drug-resistance, with resistance being highly ASM class-specific.

Preprint REVIEW | doi:10.20944/preprints202208.0008.v2

Sidney Ley

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: influenza; antivirals; umifenovir; neuraminidase inhibitors; adamantanes; cap-dependent endo-nuclease inhibitors

Online: 7 February 2023 (06:22:28 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0114.v1

Study of Technological Parameters of Antioxim Compound Medicine

Feruza Baxtiyarovna Ismailova, Holida Mannanovna Yunosova

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: dry extract; antioxidant; collection of plant; phytopreparation; antioxidant compound medicine; technological parameters

Online: 7 February 2023 (02:59:51 CET)

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Preprint REVIEW | doi:10.20944/preprints202302.0042.v1

Targeting Matrix Exopolysaccharides to Disrupt Pseudomonas aeruginosa Biofilms in Cystic Fibrosis

Jonathan Chung, Shafinaz Eisha, Subin Park, Amanda Morris, Isaac Martin

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Cystic fibrosis; Pseudomonas aeruginosa; antibiotic adjunct; anti-biofilm; biofilm-degrading enzymes; matrix exopolysaccharides; alginate oligosaccharide

Online: 2 February 2023 (09:38:31 CET)

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Preprint REVIEW | doi:10.20944/preprints202301.0528.v1

Therapeutic Properties of Polyphenols Affect AMPK Molecular Pathway in Hyperlipidemia

Mohammadjavad Sotoudeheian, SeyedAhmad Hoseini, Seyed-Mohamad-Sadegh Mirahmadi

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: AMPK; Polyphenols; Dyslipidemia; Nrf2

Online: 29 January 2023 (10:39:25 CET)

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Preprint REVIEW | doi:10.20944/preprints202212.0574.v2

Mass Spectrometry-Based Techniques Towards OMICS 2.0

Ivan Šoša

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: cost; mass spectrometry; OMICS; OMICS 2.0: Society 5.0;

Online: 27 January 2023 (06:59:30 CET)

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Preprint REVIEW | doi:10.20944/preprints202301.0449.v1

Classification, Perception, Sociological Aspects, and Toxicity of Emerging Flavored Oral Nicotine Pouches

Sadiya Bi Shaikh, Chad Newton, Wai Cheung Tung, Yehao Sun, Dongmei Li, Deborah Ossip, Irfan Rahman

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: ONPs; tobacco; nicotine; flavors; perception; toxicity; menthol

Online: 25 January 2023 (09:33:04 CET)

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Introduction: Oral Nicotine Pouches (ONPs) are the new form of nicotine pouches that have become a type of emerging smokeless tobacco product sold by various tobacco companies. These smokeless tobacco products are being marketed for usage all over as Snus containing tobacco-derived nicotine (Natural) or as tobacco-free nicotine (Synthetic) as substitutes for other tobacco products that are limited in public places. ONPs have become popular tobacco products among adolescents/young adults and over 50% of young adult users of ONP use flavored ONP, such as menthol/mint, tobacco, dessert/candy, and fruity, being the most popular flavors. Various new ONP flavors are currently popular locally as well in the online market. Tobacco, Menthol, and fruit-flavored ONPs could motivate cigarette smokers to alteration to ONPs. Methods: We expanded our knowledge on natural/synthetic ONP flavors wheels to available data on ONPs, describing in detail their flavors and brands (US and Europe) in both natural/Synthetic ONP categories. We classified over 152 snus and 228 synthetic ONPs into the following flavor categories: “Tobacco”, “Menthol/Mint”, “Fruity”, “Candy/Deserts”, “Drink”, “Aroma”, “Spices” and “Mixed Flavors”. Results: Based on total numbers, wefound that the most popular ONPs flavor sold as tobacco and menthol to be among natural ONPs, among synthetic ONPs fruity and menthol as the most prominent flavors with varying concentrations of nicotine and other flavoring chemicals including coolant WS-23. We also illustrated possible molecular targets and toxicities due to exposure to ONPs activating several signaling cascades like AKT and NF-B might possibly lead to apoptosis and epithelial mesenchymal transition (EMT). Conclusions: Considering the marketing of ONP products with various flavor profiles and most of these products containing tobacco/menthol/fruit flavor, it is likely to have regulation and marketing disclaimer on some of these products. Further, it would be logical to determine how the market reacts in terms of compliance and non-compliance with flavor restrictions by the regulatory agencies.

Preprint ARTICLE | doi:10.20944/preprints202301.0440.v1

Safety Profile of Standard and Booster Covid-19 Vaccines in Physicians in Quito-Ecuador. A Cross-Sectional Study

Nancy Jeanneth Flores-Lastra, Josue David Rivadeneira-Dueñas, Luis Ernesto Fuenmayor-González, Glenda Guayasamín-TIpanta, Michelle Jácome-García, Tamara Otzen, Carlos Manterola

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: COVID-19 Vaccines; BNT162 Vaccine; ChAdOx1 nCoV-19; Side Effects and Adverse Reactions; Booster Immunizations; COVID-19; SARS-CoV-2

Online: 25 January 2023 (03:50:52 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0371.v1

Network Pharmacological Analysis of a New Herbal Combination Targeting Hyperlipidemia and Efficacy Validation in Vitro

Tae-Hyoung Kim, Ga-Ram Yu, Hyuck Kim, Jai-Eun Kim, Dong-Woo Lim, Won-Hwan Park

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Network pharmacology; GO enrichment analysis; Key target validation; Hyperlipidemia; Hepatic steatosis; herbal combination; combinational effect; Arum ternata; Poria cocos; Zingiber officinale

Online: 20 January 2023 (06:41:44 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0305.v1

Molecular Docking and ADMET Prediction of Modified and Derivative Forms of 2-Deoxy-D-glucose against COVID-19 Main Protease Complex: In silico Approach

Rashmi Rekha Samal, Suryasikha Samal, Choudhury Suryakant Mishra, Atala Bihari Jena, Asim K Duttaroy

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Covid-19; Deoxy-D-glucose; molecular docking; ADMET

Online: 17 January 2023 (09:32:43 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0244.v2

Metformin Therapy and Breast Cancer Incidence in the Hail Region

Mhdia Osman, Taif Muqbel, Ahad Alenzi, Shuruq Alenzi, Nasrin Kalifa, Weam Khojali, Halima Mustafa Elagib, Weiam Hussein, Marwa H. Abdallah

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: breast cancer; diabetes; metformin

Online: 13 January 2023 (07:29:32 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0170.v1

Self-Micellizing Solid Dispersion of Thymoquinone with Enhanced Biopharmaceutical and Nephroprotective Effects

Shimul Halder, Sanjida Afrose, Manik Chandra Shill, Nahid Sharmin, Patricia Prova Mollick, Madhabi Lata Shuma, Md. Abdul Muhit, S. M. Abdur Rahman

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: biopharmaceutical; nephroprotective; oral absorption; self-micellizing solid dispersion; thymoquinone.

Online: 10 January 2023 (03:09:17 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0087.v1

Combination of Farnesol with Common Antifungal Drugs: Inhibitory Effect against Clinical Isolates of Candida Species

Fatemeh Nikoomanesh, Mahsa Falahati, André Luis Souza Dos Santos, Célia Fortuna Rodrigues, Shahla Roudbar Mohammadi, Mitra Rafiee, Lucia Černáková, Maryam Roudbary

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: vulvovaginal candidiasis; farnesol; azoles; resistance

Online: 5 January 2023 (02:03:12 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0050.v1

Declining Frequency of Chloroquine-resistant Haplotype of Plasmodium falciparum (CVIET) in an Endemic Area of Southwest Nigeria 17 Years After Withdrawal of Chloroquine

Abiodun I. Amusan, Olugbenga Akinola, Kazeem Akano, Maria A. Hernández-Castañeda, Jenna K. Dick, Akintunde Sowunmi, Geoffrey T. Hart, Grace Olusola Gbotosho

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Plasmodium falciparum chloroquine resistance; mutations; CVINT; malaria; allele frequency

Online: 4 January 2023 (03:04:50 CET)

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Preprint REVIEW | doi:10.20944/preprints202212.0574.v1

Mass Spectrometry-Based Techniques Towards OMICS 2.0

Ivan Šoša

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: cost; mass spectrometry; OMICS; OMICS 2.0: Society 5.0; sustainability

Online: 30 December 2022 (08:31:29 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0419.v1

Shallow and Deep-water Ophiura Species Produce a Panel of Chlorin Compounds with Potent Photodynamic Anticancer Activities

Antonina Klimenko, Robin Huber, Laurence Marcourt, Dmitry Tabakaev, Alexey Koval, Salim Sh. Dautov, Tatyana N. Dautova, Jean-Luc Wolfender, Rob Thew, Yuri Khotimchenko, Emerson Ferreira Queiroz, Vladimir L. Katanaev

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: marine organisms; chlorins; photodynamic therapy; brittle stars; Ophiuroidea; phototoxicity; cancer

Online: 22 December 2022 (05:02:21 CET)

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Preprint REVIEW | doi:10.20944/preprints202212.0276.v1

Rethinking the Paradoxical Increase in Endogenous Glucose Production in Response to Metformin: Should We Retain the Glucagon Antagonistic Effect of the Drug?

Jabeur Methnani, Taieb Ach, Aymen El Hraiech, Imed Latiri, Ali Bouslama, Monia Zaouali, Asma omezzine, Ezdine Bouhlel

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Biguanides; Antihyperglycemic agents; Liver alpha-cell axis; gluconeogenesis; Protein metabolism; insulin sensitivity

Online: 15 December 2022 (08:37:28 CET)

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Preprint REVIEW | doi:10.20944/preprints202212.0175.v1

Dexrazoxane: Exposing the Vulnerability of SARS-CoV-2

Keith McCormack

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: SARS-CoV-2; Poly(A); dexrazoxane; supramolecular self-assembly; base stacking

Online: 9 December 2022 (09:55:12 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0170.v1

Low-intensity Pulsed Ultrasound-mediated Blood-brain Barrier Opening Increases Anti-programmed Death-ligand 1 Delivery and Efficacy in Gl261 Mouse Model

Mohammed H Ahmed, Emie Quissac, Nolwenn Lemaire, Isaias Hernández-Verdín, Noël Zahr, Charlotte Schmitt, Guillaume Bouchoux, Michael Canney, M.D. Santin, Alexandra Petiet, Laura Mouton, Coralie Guerin, Lea Guyonnet, Marc Sanson, Maïté Verreault, Alexandre Carpentier, Ahmed Idbaih

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: SonoCloud; GL261 mouse model; ultrasound-mediated drug delivery; glioblastoma; immune checkpoint inhibitors

Online: 9 December 2022 (02:59:28 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0162.v1

Stability Study of Temocillin for Outpatient Parenteral Antimicrobial Therapy

Beatriz Fernández-Rubio, Laura Herrera-Hidalgo, María Victoria Gil-Navarro, Luis E López-Cortés, Jesús Rodríguez-Baño, Rafael Luque-Márquez, Arístides De Alarcón, Sonia Luque-Pardos, Autora Fernández-Polo, José María Gutiérrez-Urbón, Alicia Gutiérrez-Valencia

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Temocillin; Stability; Outpatient Parenteral Antimicrobial Therapy; Temperatures; Elastomeric devices; Infusion bags

Online: 8 December 2022 (14:32:52 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0084.v1

Relationships between Effects of Ag Nanoparticles and Ag Salt on Behavioral and Cognitive Functions of Mice and Ageing

Anna A. Antsiferova, Marina Yu. Kopaeva, Pavel K. Kashkarov

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: nanoform; nanoparticle; nanoparticles; silver; silver citrate; ageing; behavioral functions; cognitive functions; stress; individual content

Online: 6 December 2022 (01:33:04 CET)

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Preprint REVIEW | doi:10.20944/preprints202211.0221.v2

Tucaresol: A Unique Oral Candidate Drug Ideally Accessible for Treatment of COVID-19 Disease

Christopher Penney, Boulos Zacharie, Jean-Simon Duceppe

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Tucaresol; COVID-19; SARS-CoV-2; HIV; T helper cell; CD4 receptor

Online: 28 November 2022 (07:29:24 CET)

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Abstract: The SARS-CoV-2 pandemic has significantly impacted world health and economic status. In response, much work has been undertaken to provide effective, safe vaccines, antibodies and antiviral drugs with which to address this pandemic. Treatment of a pandemic population presents multiple challenges in addition to the primary issue of drug efficacy and safety, such as large scale drug manufacture and distribution, drug stability, oral dosing and pharmacoeconomic considerations. Ideally, these factors must be addressed if new candidate drugs are to be advanced for treatment of large (pandemic) populations. Subsequently, new antivirals have reached the market but choices are few. According to the NIH Covid Treatment Guidelines, only three small molecule antiviral drugs are available to treat COVID-19 disease. As such, a significant part of the research towards discovery of new antiviral drugs has focused on screening and evaluation of ‘repurposed drugs’ or previously approved or clinical stage drugs. Yet, in spite of this increased research activity, one promising clinical stage candidate drug has received little attention regarding its potential as a monotherapy or component of combination therapy for treatment of COVID-19 disease. Tucaresol, with documented human safety and pharmacokinetic data, is an orally active, stable, small molecule amenable to large scale manufacture by a proprietary two-step synthesis developed by us. Tucaresol functions as a host-targeted antiviral by selective protection/reconstitution of CD4+ T helper cells as demonstrated in HIV patients and SIV macaques. In view of similarities between HIV and SARS-CoV-2, especially with respect to host CD4+ T helper cells, and the suitability of Tucaresol for facile treatment of pandemic populations, Tucaresol is presented herein for treatment of mild-to-moderate COVID-19 patients but may also be useful for treatment of advanced disease accompanied by lymphopenia.

Preprint ARTICLE | doi:10.20944/preprints202208.0232.v3

Does Cannabidiol (CBD) in Food Supplements Pose a Serious Health Risk? Consequences of the EFSA Clock Stop Regarding Novel Food Authorisation

Dirk W. Lachenmeier, Constanze Sproll, Patricia Golombek, Stephan G. Walch

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: food safety; risk assessment; Cannabis sativa; tetrahydrocannabinol; food supplements; cannabidiol; benchmark dose; health-based guidance value (HBGV); liver toxicity

Online: 24 November 2022 (02:53:03 CET)

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Preprint REVIEW | doi:10.20944/preprints202211.0433.v1

Modification Strategies for Ionic Complementary Self-Assembling Peptides: Taking RADA16-Ⅰ as an Example

Weiwei Guo, Yinping Ma, Lei Hu, Yujie Feng, Yanmiao Liu, Xuedong Yi, Wenzhi Zhang, Fushan Tang

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: hydrogel; active motifs modification; regenerative medicine; Self-assembling peptide

Online: 23 November 2022 (05:11:24 CET)

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Preprint REVIEW | doi:10.20944/preprints202211.0271.v1

Revisiting the Anti-cancer Toxicity of Clinically Approved Platinating Derivatives

Benjamin N. Forgie, Rewati Prakash, Carlos M. Telleria

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: cisplatin; carboplatin; oxaliplatin; cellular uptake; DNA damage; transcription regulation; non-nuclear targets; chemoresistance; mechanisms of action; clinical usages; influx and efflux pumps; ribosome biogenesis; ER stress response; immunogenic cell death; interstrand and intrastrand DNA cross-links.

Online: 15 November 2022 (03:38:06 CET)

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Preprint REVIEW | doi:10.20944/preprints202211.0221.v1

Tucaresol: A Unique Oral Candidate Drug Ideally Accessible for Treatment of COVID-19 Disease

Christopher Penney, Boulos Zacharie, Jean-Simon Duceppe

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Tucaresol; COVID-19; SARS-CoV-2; HIV; T helper cell; CD4 receptor

Online: 11 November 2022 (07:52:38 CET)

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Abstract: The SARS-CoV-2 pandemic has significantly impacted world health and economic status. In response, much work has been undertaken to provide effective, safe vaccines, antibodies and antiviral drugs with which to address this pandemic. Treatment of a pandemic population presents multiple challenges in addition to the primary issue of drug efficacy and safety, such as large scale drug manufacture and distribution, drug stability, oral dosing and pharmacoeconomic considerations. Ideally, these factors must be addressed if new candidate drugs are to be advanced for treatment of large (pandemic) populations. Subsequently, new antivirals have reached the market but choices are few. According to the NIH Covid Treatment Guidelines, only three small molecule antiviral drugs are available to treat COVID-19 disease. As such, a significant part of the research towards discovery of new antiviral drugs has focused on screening and evaluation of ‘repurposed drugs’ or previously approved or clinical stage drugs. Yet, in spite of this increased research activity, one promising clinical stage candidate drug has received little attention regarding its potential as a monotherapy or component of combination therapy for treatment of COVID-19 disease. Tucaresol, with documented human safety and pharmacokinetic data, is an orally active, stable, small molecule amenable to large scale manufacture by a proprietary two-step synthesis developed by us. Tucaresol functions as a host-targeted antiviral by selective protection/reconstitution of CD4+ T helper cells as demonstrated in HIV patients and SIV macaques. In view of similarities between HIV and SARS-CoV-2, especially with respect to host CD4+ T helper cells, and the suitability of Tucaresol for facile treatment of pandemic populations, Tucaresol is presented herein for treatment of mild-to-moderate COVID-19 patients but may also be useful for treatment of advanced disease accompanied by lymphopenia.

Preprint ARTICLE | doi:10.20944/preprints202211.0188.v1

Direct in Vivo Comparison of ^99mTc-labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy

Vladimir Tolmachev, Vitalina Bodenko, Maryam Oroujeni, Sergey Deyev, Elena Konovalova, Alexey Schulga, Sarah Lindbo, Sophia Hober, Olga Bragina, Anna Orlova, Anzhelika Vorobyeva

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: radionuclide molecular imaging; HER2; scaffold proteins; DARPin; ADAPT6; technetium-99m; preclinical

Online: 10 November 2022 (03:31:20 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202211.0154.v1

Aésculus hippocástanum: Phytoscreening, Antiradical Activity, and Anti-Inflammatory Effect

Albina Filatova, Luiza Azimova, Ulugbek Gayibov, Abboskhon Turaev, Takhir Aripov, Sabina Gayibova

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: chestnut; stable radical; phytoconstituents; swelling

Online: 8 November 2022 (10:30:57 CET)

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Preprint REVIEW | doi:10.20944/preprints202211.0122.v1

Endocannabinoid System: Chemical Characteristics and Biological Activity

Guilherme Montes

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Endocannabinoid system; receptor cannabinoid; endocannabinoids ligands; phytocannabinoids; Integrative and Complementary Health Practices

Online: 7 November 2022 (11:36:46 CET)

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Preprint ARTICLE | doi:10.20944/preprints202211.0089.v1

Tibouchina granulosa Leaves Presents Anti-Inflammatory Effect

Carolina Carvalho Guilhon, Alan Silva Minho, Marc Pouliot, Fabio Boylan, Patricia Dias Fernandes

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Tibouchina granulosa; anti-inflammatory activity; hispiduloside; cytokines

Online: 4 November 2022 (07:24:02 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202211.0063.v1

In vivo Acute Toxicity Studies of Novel Melanoma Actives

Sadeeshkumar Velayutham, Trisha Seal, Samaya Danthurthy, Julia Zaias, Keiran S.M. Smalley, Dmitriy Minond

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: melanoma; drug discovery; spliceosomal inhibition; acute toxicity; blood chemistry; organ histopathology

Online: 3 November 2022 (01:43:05 CET)

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Preprint REVIEW | doi:10.20944/preprints202210.0484.v1

Use of Intra-Articular Injection Corticosteroid Injections to the First Metatarsophalangeal Joint. First Theme of a Scoping Review

Ian Reilly, Rajesh Botchu

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Steroid injection; synovial joint; first metatarsophalangeal joint; hallux limitus; hallux rigidus; hallux valgus; gout; arthrofibrosis

Online: 31 October 2022 (10:27:07 CET)

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Preprint ARTICLE | doi:10.20944/preprints202210.0459.v1

Phenylbenzohydrazides Obtained from Isatoic Anhydride Present Anti-Inflammatory Activity in Vivo and in Vitro

João Pedro Barros de Paiva, Millena Santos Cordeiro, Patricia Ribeiro de Carvalho França, Luiz Octavio Pereira Branco, Isabela Souza dos Santos, Nanashara Figueiredo Reis, Patrick Pedro Pimentel, Thais Biondino Sardella Giorno, Evanoel Crizanto de Lima, Patricia Dias Fernandes

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Phenylbenzohydrazides; isatoic anhydride; inflammation; anti-inflammatory substance; carrageenan-induced inflammation; nitric oxide

Online: 31 October 2022 (01:02:02 CET)

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Preprint ARTICLE | doi:10.20944/preprints202210.0281.v1

COVID -19 Pandemic Diseases Effect on Self-Medication Practices Among Community of Bedelle City and Its Surrounding, Buno Bedelle Zone, South West of Oromia, Ethiopia

Wakuma Wakene Jifar, Osman Mohammed Oumer, Ismael Indris Muhammed

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Covid-19; Medicine; Practice; Bedelle city; Self-Medication

Online: 19 October 2022 (10:09:14 CEST)

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Preprint REVIEW | doi:10.20944/preprints202210.0189.v1

Acetaminophen Causes Neurodevelopmental Injury in Susceptible Babies and Children: No Valid Rationale for Controversy

Lisa Zhao, John P. Jones, Lauren G. Anderson, Zacharoula Konsoula, Cynthia D. Nevison, Kathryn J. Reissner, William Parker

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: acetaminophen; autism; paracetamol; neurodevelopment

Online: 13 October 2022 (08:00:33 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202210.0168.v1

Health Risk Assessment of Dermal Exposure to Polycyclic Aromatic Hydrocarbons from the Use of Infant Diapers

Alfred Bernard, Dudler Vincent

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: diaper; polycyclic aromatic hydrocarbons; skin cancer; neurobehavioral changes

Online: 12 October 2022 (09:55:13 CEST)

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Preprint REVIEW | doi:10.20944/preprints202210.0148.v1

Virtual Screening and Zebrafish Models in Tandem, for Drug Discovery and Development

David Hernández-Silva, Francisca Alcaraz-Pérez, Horacio Pérez-Sánchez, María Luisa Cayuela

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: drug development; high throughput screening; in vivo/in silico screening; zebrafish

Online: 11 October 2022 (10:33:33 CEST)

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Preprint REVIEW | doi:10.20944/preprints202210.0142.v1

Employ of Anthocyanins in nanocarriers for Nano Delivery: In Vitro and In Vivo Experimental Approaches for Chronic Diseases

Ana C. Gonçalves, Amícal Falcão, Gilberto Alves, João A. Lopes, Luís R. Silva

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: bioactive compounds; anthocyanins; drug delivery system; nanoparticles; chronic diseases; health benefits

Online: 11 October 2022 (05:04:19 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202210.0104.v1

Polio Eradication or Comeback? Outcome Reporting Bias in the 1954 Poliomyelitis Vaccine Field Trial

Ronald B. Brown

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: polio; paralytic poliomyelitis; Salk vaccine field trial; inactivated polio vaccine; vaccine efficacy; relative risk reduction; absolute risk reduction; number needed to vaccinate; acute flaccid paralysis; polio eradication; mass vaccination

Online: 9 October 2022 (03:16:35 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202210.0058.v1

Advanced Epi-X4 Derivatives Covalently Bind Human Serum Albumin Resulting in Prolonged Plasma Stability

Armando Rodríguez-Alfonso, Astrid Heck, Yasser Ruiz-Blanco, Andrea Gilg, Ludger Ständker, Seah Ling Kuan, Tanja Weil, Elsa Sanchez-Garcia, Sebastian Wiese, Jan Münch, Mirja Harms

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: EPI-X4; albumin carrier; peptide stability; CXCR4 antagonist;

Online: 6 October 2022 (08:50:49 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202210.0050.v1

Comparative Preclinical Evaluation of Peptide-Based Chelators for Labeling of DARPin G3 with 99mTc for Radionuclide Imaging of HER2 Expression in Cancer

Maria Larkina, Evgenii Plotnikov, Ekaterina Bezverkhniaia, Yulia Shabanova, Maria Tretyakova, Feruza Yuldasheva, Roman Zelchan, Alexey Schulga, Elena Konovalova, Anzhelika Vorobyeva, Javad Garousi, Torbjörn Gräslund, Mikhail Belousov, Vladimir Tolmachev, Sergey M. Deyev

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: radionuclide; HER2; DARPin; SPECT; 99mTc; imaging; cancer

Online: 6 October 2022 (08:09:37 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202210.0038.v1

Minimalised Three-Dimensional Human Midbrain In Vitro Model for Neurotoxicity Evaluation of DYRK1 Inhibitors

Xiao Wan, Vincent Fagan, Paul Brennan, Daniel Ebner

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: three-dimensional in vitro model; DYRK1; human midbrain; neural progenitor cells

Online: 5 October 2022 (11:29:38 CEST)

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Preprint REVIEW | doi:10.20944/preprints202209.0458.v1

Potential Inflammatory Biomarker in Patients with Attention Deficit Hyperactivity Disorder

Ji Hyun Park

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: kynurenine pathway; inflammatory biomarkers; inflammation; ADHD; neurobiology; kynurenine

Online: 29 September 2022 (08:11:33 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0371.v1

Bioefficacy of Hydroxytyrosol-Rich Food Supplements on Preventing Lipid Peroxidation in Healthy Men

Cecilia Bender, Ilaria Candi, Eva Rogel

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: olive phenolics; hydroxytyrosol; oxidized LDL; ox-LDL; isoprostanes; F2-isoprostanes

Online: 23 September 2022 (10:23:51 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0310.v1

Systematic Down-Selection of Repurposed Drug Candidates for COVID-19

Christopher A. MacRaild, Muzaffar-Ur-Rehman Mohammed, Faheem Faheem, Sankaranarayanan Murugesan, Ian K. Styles, Amanda L. Peterson, Carl M.J. Kirkpatrick, Matthew A. Cooper, Enzo A. Palombo, Moana M. Simpson, Hardik Ashish Jain, Vinti Agarwal, Alexander J. McAuley, Anupama Kumar, Darren J. Creek, Natalie L. Trevaskis, Seshadri S. Vasan

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: COVID-19; CoviRx.org; database; drugs; pandemic; repurposing; SARS-CoV-2; therapies; treatments; Variants of Concern (VOC)

Online: 20 September 2022 (15:00:48 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202208.0171.v2

Drug Combinations to Prevent Antimicrobial Resistance: Some Correlations and Laws, and their Verifications, thus Proposing Some Principles and a Preliminary Scheme

Houqin Yi, Ganjun Yuan, Shimin Li, Xuejie Xu, Yingying Guan, Li Zhang, Yu Yan

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: combination; antimicrobial resistance; selection index; collateral sensitivity; mutant prevention concentration; minimal inhibitory concentration; fractional inhibitory concentration index; stress factor

Online: 13 September 2022 (07:53:32 CEST)

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Antimicrobial resistance (AMR) has been a serious threat to human health, and combination therapy is proved to be an economic and effective strategy to fight the resistance. However, the abuse of drug combinations would conversely accelerate the spread of AMR. In our previous work, it had been concluded that the mutant selection indexes (SIs) of one agent against a specific bacterial strain are closely related to the proportions of two agents in a drug combination. To discover probable correlations, predictors and laws for further proposing feasible principles and schemes guiding the AMR-preventing practice, here three aspects were further explored. First, the power function (y=ax^b, a > 0) correlation between the SI (y) of one agent and the ratio value (x) of two agents in a drug combination was further established based on the mathematical and statistical analyses for those experimental data, and two rules a₁ × MIC₁ = a₂ × MIC₂ and b₁ + b₂ = -1 were discovered from both equations of y=a₁x^b1 and y=a₂x^b2 respectively for two agents in drug combinations. Simultaneously, it was found that one agent with larger MPC alone for drug combinations show greater potency for narrowing itself MSW and preventing the resistance. Second, a new concept as mutation-preventing selection index (MPSI) was proposed and used for evaluating the mutation-preventing potency difference of two agents in drug combinations, and the positive correlation between the MPSI and the mutant prevention concentration (MPC) or minimal inhibitory concentration (MIC) was subsequently established. Inspired by this, the significantly positive correlation, contrary to previous reports, between the MIC and the corresponding MPC of antimicrobial agents against pathogenic bacteria was established using one hundred and eighty-one of data pairs reported. These results together of above three aspects indicate that the MPCs in alone and combination are very important indexes for drug combinations to predict the mutation-preventing effects and the trajectories of collateral sensitivity, and while the MPC of an agent can be roughly calculated from its corresponding MIC. Subsequently, the former conclusion was further verified and improved by the antibiotic exposure to forty-three groups designed as different drug concentrations and various proportions. The results further proposed that the C/MPC for the agent with larger proportion in drug combinations can be considered as a predictor and is the key to judge whether the resistance and the collateral sensitivity occur to two agents. Based on these above correlations, laws, and their verification experiments, some principles were proposed, and a diagram of the mutation-preventing effects and the resistant trajectories for drug combinations with different concentrations and ratios of two agents was presented. Simultaneously, the reciprocal of MPC alone (1/MPC), proposed as the stress factors of two agents in drug combinations, together with their SI in combination, is the key to predict the mutation-preventing potency and control the trajectories of collateral sensitivity. Finally, a preliminary scheme for antimicrobial combinations preventing the AMR was further proposed for subsequent improvement research and clinic popularization, based on the above analyses and discussion. Moreover, some similar conclusions were speculated for triple or multiple drug combinations.

Preprint ARTICLE | doi:10.20944/preprints202208.0232.v2

Does Cannabidiol (CBD) in Food Supplements Pose a Serious Health Risk? Consequences of the EFSA Clock Stop Regarding Novel Food Authorisation

Dirk W. Lachenmeier, Constanze Sproll, Patricia Golombek, Stephan G. Walch

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: food safety; risk assessment; Cannabis sativa; tetrahydrocannabinol; food supplements; cannabidiol; benchmark dose; reference dose; liver toxicity

Online: 5 September 2022 (04:34:49 CEST)

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Preprint REVIEW | doi:10.20944/preprints202208.0542.v1

The Immunomodulating Properties of Noni Juice

Brett J. West

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Noni juice; Morinda citrifolia; immune system; immunomodulation

Online: 31 August 2022 (09:02:28 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202208.0504.v1

Development and Validation of UPLC-Qtof-MS Method for Blood Analysis of Amphetamine-Related Drug Isomers

Ahmad Alamir, James Watterson, Ibraheem Attafi

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Amphetamine-related drugs; Forensic Toxicology; blood; UPLC-qTOF-MS; MMSPE; Validation; SWGTOX

Online: 30 August 2022 (04:09:57 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202208.0232.v1

Does Cannabidiol (CBD) in Food Supplements Pose a Serious Health Risk? Consequences of the EFSA Clock Stop Regarding Novel Food Authorisation

Dirk W. Lachenmeier, Constanze Sproll, Patricia Golombek, Stephan G. Walch

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: food safety; risk assessment; Cannabis sativa; tetrahydrocannabinol; food supplements; cannabidiol; benchmark dose; reference dose; liver toxicity

Online: 12 August 2022 (09:00:49 CEST)

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Preprint REVIEW | doi:10.20944/preprints202208.0212.v1

Potential Drug Targets and Treatment Options for Covid-19: A Review

Muluken Wubetu

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: COVID-19; Drug targets; Inflammation; Treatment Options; Vaccines

Online: 11 August 2022 (08:07:05 CEST)

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Preprint REVIEW | doi:10.20944/preprints202208.0194.v1

Sarfaraz K. Niazi

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: biosimilar; analytical assessment; animal testing; clinical pharmacology; clinical efficacy; FDA; EMA; MHRA; WHO

Online: 10 August 2022 (05:19:49 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202208.0171.v1

Drug Combinations to Prevent Antimicrobial Resistance: Some Correlations, Rules and Laws, and a Preliminary Scheme

Houqin Yi, Ganjun Yuan, Shimin Li, Xuejie Xu, Yingying Guan, Li Zhang, Yu Yan

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: combination; antimicrobial resistance; selection index; collateral sensitivity; mutant prevention concentration; minimal inhibitory concentration; fractional inhibitory concentration index; stress factor

Online: 9 August 2022 (04:19:53 CEST)

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Antimicrobial resistance (AMR) has been a serious threat to human health, and combination therapy is proved to be an economic and effective strategy to fight the resistance. However, the abuse of drug combinations would conversely accelerate the spread of AMR. To guide the practice, some regularity conclusions had been drawn in our previous work. Based on those experimental data, here the power function (y=ax^b, a>0) correlation between the mutant selection index (SI) (y) of one agent and the ratio value (x) of two agents in a drug combination was established, and two rules a₁ × MIC₁ = a₂ × MIC₂ and b₁ + b₂ = -1 were discovered from both equations of y=a₁x^b1 and y=a₂x^b2 for two agents in drug combinations. Simultaneously, it was found that one agent with larger MPC alone for drug combinations would present a larger |b| and show greater potency for narrowing itself MSW and preventing the resistance. Another, a new concept as mutation-preventing selection index (MPSI) was proposed and used for evaluating the mutation-preventing potency difference of two agents in drug combinations, and the positive correlation between the MPSI and the mutant prevention concentration (MPC) or minimal inhibitory concentration (MIC) was subsequently established. Inspired by this, the significantly positive correlation, contrary to previous reports, between the MIC and the corresponding MPC of antimicrobial agents against pathogenic bacteria was established using one hundred and eighty-one of data pairs reported. These above together indicate that the MPCs in alone and combination are very important indexes for drug combinations to predict the mutation-preventing effects and the trajectories of collateral sensitivity, and the MPC of an agent can be roughly calculated from its corresponding MIC. Subsequently, this was further verified and improved by the antibiotic exposure to forty-three groups designed as different drug concentrations and various proportions. Based on these, the diagram of the mutation-preventing effects and the resistant trajectories of drug combinations with different concentrations and ratio of two agents was presented, and the C/MPC for the agent with larger proportion in drug combinations is the key to judge whether the resistance and the collateral sensitivity occur to two agents. Furthermore, the stress factors 1/MPC alone of two agents, together with their SI in combination, are the key to predict the mutation-preventing effects, and control the trajectories of collateral sensitivity. Combined the discussion and analyses for the above results and previous work, a preliminary scheme for antimicrobial combinations preventing the AMR was further proposed for subsequent improvement research and clinic popularization. Moreover, some other proposals and regularity conclusions related to preventing the AMR, involving fractional inhibitory concentration index (FICI), mutant selection index (SI), and pharmacokinetic parameters (t_1/2, AUC₂₄/MPC, C_max/MPC, and f %T > MPC, etc.), were analyzed and discussed, and finally some similar conclusions were speculated for triple or multiple drug combinations.

Preprint ARTICLE | doi:10.20944/preprints202208.0144.v1

Surface Modification of Biodegradable Microparticles With the Novel Host-Derived Immunostimulant CPDI-02 Significantly Increases Short-Term and Long-Term Mucosal and Systemic Antibodies Against Encapsulated Protein Antigen in Young Naïve Mice After Respi

Jacob E. Parriott, Jason P. Stewart, Derek D. Smith, Stephen M. Curran, Christopher D. Bauer, Todd A. Wyatt, Joy A. Phillips, Elizabeth R. Lyden, Geoffrey M. Thiele, Joseph Anthoney Vetro

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: mucosal immunization; mucosal vaccine; vaccine delivery; administration volume; targeted vaccines; M cell targeting; dendritic cell targeting; C5aR1; C5a1R; CD88; EP54; EP67

Online: 8 August 2022 (10:17:30 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202208.0135.v1

The Impact of Low Cardiac Output on Propofol Pharmacokinetics across Age Groups - an Investigation using Physiologically based Pharmacokinetic Modelling

Karel Allegaert, Mohammad Yaseen Abbasi, Robin Michelet, Olusola Olafuyi

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: physiologically based pharmacokinetic modelling; propofol; low cardiac output; pharmacokinetics; neonate; developmental pharmacology; asphyxia; hypothermia; pediatrics; pharmacokinetics

Online: 8 August 2022 (06:12:36 CEST)

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Preprint REVIEW | doi:10.20944/preprints202208.0021.v1

Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics

Arvind Kumar Singh Chandel, Dixit Bhalani, Nutan Bhingaradiya, Avinash Kumar

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Solubility; Bioavailability; Dissolution; Poorly Soluble Drugs; Drug Solubility Enhancement Techniques

Online: 1 August 2022 (10:44:13 CEST)

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The low water solubility of any pharmacoactive molecules limits their pharmacological potential but the solubility parameter cannot compromise, so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, the oral dosage forms cover more than 50 %, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry screening programs identified that around 40% of new chemical entities (N.C.E.s) face various difficulties at the formulation and development step. These pharmaceuticals are attributed to their less solubility and bioavailability. The bioavailability and drug solubility enhancement are significant challenges in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibits poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of the poorly water-soluble drug, for example, complexation of active molecules, utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelles preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, by some appropriate research reports.

Preprint REVIEW | doi:10.20944/preprints202208.0008.v1

Understanding Anti-Influenza Antiviral Drugs

Sidney Ley

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: influenza; antivirals; anti-influenza; influenza drugs; the flu

Online: 1 August 2022 (05:41:34 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202207.0411.v1

A Combined Cell-Worm Approach to Search for Compounds Counteracting the Toxicity of Tau Oligomers in Vivo

Carmina Natale, Maria Monica Barzago, Luca Colnaghi, Ada De Luigi, Franca Orsini, Luana Fioriti, Luisa Diomede

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: tauopathy; tau protein; oligomers; proteotoxicity; C. elegans; tetracyclines.

Online: 27 July 2022 (05:10:20 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202207.0214.v1

In-vitro Study of Chemical Composition, Antimicrobial and Antioxidant Properties of Adiantum capillus-veneris L. Essential Oil

Iman Nasrollahi, Ebrahim Talebi, Zahra Bashardoost

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Adiantum capillus-veneris L.; Chemical compounds; Antioxidant; Antimicrobial; Essential oil; DPPH

Online: 14 July 2022 (11:32:37 CEST)

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Preprint REVIEW | doi:10.20944/preprints202207.0040.v1

A Review of the Pharmacognostical and Pharmacological Properties of The Kalanchoe Plant as Treatment for Dermatological-Related Conditions

Fawzijamil dela Cruz

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Kalanchoe; antibacterial; anti-inflammatory properties; wound healing; antioxidant

Online: 4 July 2022 (08:27:24 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202207.0004.v1

A Hybrid AI-driven Algorithm to Uncover Potential Therapeutic Targets for COVID-19 Using Network-based Drug Repurposing

Carlos Marchi, David Corrêa Martins Jr.

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: SARS-CoV-2; COVID-19; drug repurposing; artificial intelligence; target-target similarity network; drug-target interaction network

Online: 1 July 2022 (05:33:16 CEST)

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Preprint REVIEW | doi:10.20944/preprints202206.0305.v1

Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu

Deanna V. Maybee, Nicole L. Ink, Mohammad A.M. Ali

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Matrix metalloproteinases (MMPs); MMP-2; MT1-MMP; intracellular roles; subcellular localization

Online: 22 June 2022 (05:19:01 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202206.0274.v1

α-amylase Inhibition Activity of Phytoconstituents Present in the Roots Of Cyclea peltata-An in-silico and in-vitro Investigation

Gandhimathi R., Binoy Varghese Cheriyan, Deevan Paul A., Saravanakumar A., Lakshmanan G.

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Cyclea peltata; Diabetes Mellitus; Docking; Schrodinger; Alpha amylase; Inhibition

Online: 20 June 2022 (14:33:11 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202205.0193.v1

In Vitro Bovine Embryo Production Using Medium’s Supplemented with Recombinant Human Galectin-1 Buffered

Marcelo Roncoletta, Erika da Silva Carvalho Morani, Nathalia Adrielli Agassi De Salles, Guilherme Camargo Ferraz

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Tolerana®; Pregnancy; Fetal-Maternal Recognition; Reproduction; Reproductive Safety Toxicology

Online: 13 May 2022 (15:14:42 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202205.0094.v1

A Randomized, Placebo Controlled, Double Blinded, Parallel Group Clinical Study to Evaluate the Efficacy and Safety of AEV01 for Mild COVID19 in Elderly Patients at Risk of Complications

RAMESH KANNAN, VANITHA MURALIKUMAR, VAMSEEDHAR ANNAM, SAKTHI BALAN, ARAVINDA KUMAR, SEKHAR MM, RENU MEDASANI

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: COVID-19; Picrorhiza kurroa; AEV01; NEW Score; Immunomodulatory; unvaccinated elderly population

Online: 7 May 2022 (05:47:32 CEST)

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Background: While several drugs are in the pipeline for treatment of various grades of COVID-19 disease, none of them have shown promise until now. Medicinal plants are crucial in developing and developed countries for their primary and basic health needs owing to better tolerability, superior compatibility with human body and having lesser side effects. AEV01 , a speciality extract of kutki (Picrorhiza kurroa), is one potential medicinal herb which can be effective for mild COVID19 in elderly patients at risk of complications and aging immunity. Purpose: The efficacy and safety of AEV01 for mild COVID-19 in elderly patients at risk of complications was investigated in this study. Study design: A prospective, phase 3, randomized, multicentric, placebo controlled double blinded parallel group interventional trial. Methods: This study was conducted in elderly patients diagnosed as COVID-19 with mild symptoms. 70 patients were randomized into two groups to receive AEV01 capsule (100mg) and placebo respectively thrice daily for 30 days along with standard care of treatment as per national WHO/ICMR guidelines. Clinical improvement timelines and corresponding scores using 8-point ordinal scale and NEWS were assessed for efficacy and safety of AEV01 in COVID-19 patients. Results: AEV01 group showed a significant improvement (P=0.0001) in the normalization of the SpO₂ rate and relief from cough. There was also significant difference in time to recovery, with patients in the AEV01 drugtreated group recovering in 4.5 days as compared to Placebo in 9.1 days. ESR, LDH, serum ferritin, Neutrophil-Lymphocyte ratio (NLR), TNF- alpha, IL-6 and CD4 cell counts, which are considered as prognostic markers in COVID19 infected patients, showed a significant improvement in patients treated with AEV01. The AEV01 drug treated group showed significant clinical improvement in the 8-point ordinal scale severity rating and NEW Score from day 3 onwards which continued up to end of study. Conclusion: AEV01 has shown a significant improvement in clinical and laboratory parameters. There was also reduction in the progression of the COVID-19 disease in unvaccinated elderly patients from mild to moderate when treated at an earlier stage.

Preprint REVIEW | doi:10.20944/preprints202205.0051.v1

A Reality We Have to Face in the Era of Tenofovir-Derived Pre-exposure Prophylaxis and Antiretroviral Therapy: A Paradigm Shift From the Reduction of HIV Risk to the Increased Risk of Cardiovascular Disease?

Jason Lew, Ilias Yee

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Tenofovir; Pre-exposure prophylaxis; anti-retroviral therapy; cardiovascular disease; LGBT

Online: 5 May 2022 (16:11:31 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202205.0028.v1

Phase I Trial of ^99mTc-1-Thio-D-glucose for Imaging of Lymphomas

Vladimir Chernov, Ekaterina Dudnikova, Roman Zelchan, Anna Medvedeva, Anstasiya Rybina, Olga Bragina, Viktor Goldberg, Albina Muravleva, Jens Sörensen, Vladimir Tolmachev

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: 99mTc-1-Thio-D-glucose; single-photon emission computed tomography; Lymphoma; Hodgkin's lymphoma; non-Hodgkin's lymphomas

Online: 5 May 2022 (09:24:01 CEST)

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Preprint REVIEW | doi:10.20944/preprints202204.0271.v1

Traditional Uses, Phytochemistry and Pharmacological Activities of Annona Genus

Bassam Salem M. Al Kazman, Jane Rouse Hanrahan

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Annonaceae; Annona; custard apple; phytochemistry; bioactivity; pharmacological activity

Online: 28 April 2022 (04:16:02 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202204.0119.v1

GC–MS Based Metabolites Profiling, In Vitro Antioxidant, Antibacterial, and Anti-Cancer Properties of Different Solvent Extracts from Leaves, Stems, Roots, and Flowers of Micromeria fruticosa (Lamiaceae)

Ibrahim Abu-Reidah, Mohamed Al-Nuri, Anwar Afifi, Ghadeer Omar, Ghalib Adwan, Ismail Warad

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Micromeria fruticosa; GC-MS; metabolites; anticancer activity; MTT; antioxidant activity; antimicrobial activity

Online: 13 April 2022 (08:29:56 CEST)

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This study assesses the secondary metabolites, minerals, antimicrobial, antioxidant, and anticancer properties of Micromeria fruticosa plant different botanical parts (leaf, stem, root, flower) extracted with various solvents. The plant samples were sequentially obtained using different solvents (n-hexane, ethanol and water) through steeping. Then, each of the extracts was further analyzed by using gas chromatography–mass spectrometry (GC-MS). Moreover, the extracts were bio-assayed to test their antioxidant, antibacterial, and anti-cancer activities. Quali-quantitative analysis of M. fruticosa crude extracts revealed the occurrence of 27 secondary metabolites were identified including mainly monoterpenes, sesquterpenes, and fatty acids, with varying quantities. Some of the major bioactive compounds included, Menthone (5.42-30.05%), Oleamide (3.40-32.20%), Pulegone (10.66-64.1%), and Menthol (3.61-100.0%), which were detected mostly in all plant parts with significant quantities. Several antioxidant minerals, mainly, Fe, Zn, and Mn, were detected with the highest amounts in the Micromeria water extracts. Results from antimicrobial assays showed that the water extract of leaves exhibited the highest DPPH scavenging activity (89.73%) followed by the water extract of flowers (80.07%) at a concentration of 100 μg/mL. The water extract of stems showed greater antimicrobial activity against all the tested gram negative and positive bacteria (Methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, Escherichia coli, and Shigella sonnie). The leaves ethanolic and stem aqueous extracts had a strong antimicrobial activity against E. coli. and C. albicans. Flower aqueous extract demonstrated the highest cytostatic effect on the colon cell line by reducing viability up to 30.4%, followed by the leaf ethanol extract with 38.6% cell viability reduction at 1000 µg/mL. In conclusion, extraction solvents influenced the recovery of phytocompounds and the highest pharmacological activities of the different extracts could be correlated to the presence of additional bioactive compounds. Our results suggest that M. fruticosa plant is a promising source of natural products with antioxidant, anti-microbial and anti-cancer properties for potential nutraceutical, therapeutic, and functional food applications. , , , , , ,

Preprint REVIEW | doi:10.20944/preprints202204.0054.v1

Medical Cannabis - A Historical Perspective

Helena Freitas

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Medical Cannabis; history of cannabis; medicine; cannabinoids

Online: 7 April 2022 (04:14:19 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202204.0037.v1

Clinical Characteristics of Ciguatera Fish Poisoning in Martinique, French West Indies – A Case Series

Dabor Resiere, Jonathan Florentin, Hossein Mehdaoui, Zakaria Mahi, Papa Gueye-Ngalgou, Didier Hommel, Jean Pujo, Flaubert Nkont'cho, Aurélie Boisnoir, Patrick Portecop, Remi Neviere, Hatem Kallel, Bruno Megarbane

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Ciguatera; Ciguatoxin; Fish; French West Indies; Martinique; Poisoning

Online: 6 April 2022 (08:34:43 CEST)

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Ciguatera fish poisoning (CFP) is one of the most common causes worldwide of marine poisoning associated with fish consumption from tropical areas. Its incidence is underreported. CFP cases seem to increase with grouped cases reported during summer. Exposure to ciguatoxin, the toxin responsible for CFP with sodium-channel agonistic, cholinergic, and adrenergic activities, may result in a large spectrum of manifestations. We aimed to describe the clinical characteristics, management, and outcome of CFP in Martinique, French West Indies. We conducted an observational retrospective single-center study for six years (October 2012 to September 2018) including all CFP patients managed by the prehospital medical services, admitted to the university hospital emergency department, or declared to the regional health agency. One hundred and forty-nine CFP patients (81females/63males; median age, 46 years [interquartile range, 34-61]) were included. Acute features consisted of general (91%; mainly, myalgia pruritus, and asthenia), gastrointestinal (90%; mainly diarrhea, abdominal pain, and nausea), neurological (72%; mainly, paresthesia, dysgeusia, and impairment of hot/cold feeling), and cardiovascular manifestations (22%; bradycardia, hypotension, and heart conduction disorders). Management was supportive. No patient died but symptoms persisted in 40% of the 77 patients with follow-up on day 15. CFP was mainly attributed to the ingestion of trevallies (59%), snappers (13%), and king mackerels (8%) with collective contaminations (71%). Unusual fish (tuna, salmon, and spider conchs) were suspected in rare cases. Ingestion of trevallies was associated with significantly higher persistent symptoms (odds ratio, 3.00; 95% confidence interval, [1.20-8.00]; p=0.03). CFP incidence was 0.67 cases per 10,000 patient-years in Martinique over the study period. To conclude, CFP represents an increasing public health issue in Martinique like in other Caribbean islands. Patients present usual but possibly life-threatening features. The outcome is excellent despite frequently prolonged manifestations.

Preprint ARTICLE | doi:10.20944/preprints202203.0117.v3

Compounded Nonsterile Preparations and FDA-Approved Commercially Available Liquid Products for Children: A North American Update

Richard Parrish, Lisa D. Ashworth, Raimar Löbenberg, Sandra Benavides, Jeffrey J. Cies, Robert B. MacArthur

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: active pharmaceutical ingredient; compounded drug; compounding; extemporaneous formulation; manufactured material; medication; monograph; pediatric; reference standards

Online: 5 April 2022 (10:17:10 CEST)

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Preprint REVIEW | doi:10.20944/preprints202202.0313.v3

The Role of Seawater and Saline Solutions in Treatment of Respiratory Conditions

Danijela Štanfel, Livije Kalogjera, Sergej V. Ryazantsev, Kristina Hlača, Elena Y. Radtsig, Rashidov Teimuraz, Pero Hrabač

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: seawater; seawater preparation; Aqua Maris; nasal irrigation; upper respiratory track; otorhinolaryngology

Online: 21 March 2022 (09:16:41 CET)

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Preprint ARTICLE | doi:10.20944/preprints202203.0235.v1

Antimicrobial Prescribing Confidence and Knowledge Regarding Drug Resistance: Perception of Medical Students in Malaysia and the Implications

Mainul Haque, Tasim Ara, Md. Ahsanul Haq, Halyna Lugova, Siddhartha Dutta, Nandeeta Samad, Abdullahi Rabiu Abubakar, Sharifah Shasha Binti Syed Mohdhar, Md. Mahabubur Rahman, Salequl Islam, Nihad Adnan, Rahnuma Ahmad, Shahidah Leong Binti Abdullah, Mohd Hafizi Bin Ismail, Brian Godman

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Antimicrobial; Prescribing; Drug Resistance; Knowledge; Perception; Medical Students; Malaysia

Online: 16 March 2022 (14:44:53 CET)

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Preprint ARTICLE | doi:10.20944/preprints202203.0117.v2

Compounded Nonsterile Preparations and FDA-Approved Commercially Available Liquid Products for Children: A North American Update

Richard Parrish, Lisa D. Ashworth, Raimar Löbenberg, Sandra Benavides, Jeffrey J. Cies, Robert B. MacArthur

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: active pharmaceutical ingredient; compounded drug; compounding; extemporaneous formulation; manufactured material; medication; monograph; pediatric; reference standards

Online: 10 March 2022 (08:26:21 CET)

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Preprint ARTICLE | doi:10.20944/preprints202203.0117.v1

Compounded Nonsterile Preparations and FDA-Approved Commercially Available Liquid Products for Children: A North American Update

Richard Parrish, Lisa D. Ashworth, Raimar Löbenberg, Sandra Benavides, Jeffrey J. Cies, Robert B. MacArthur

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: active pharmaceutical ingredient; compounded drug; compounding; extemporaneous formulation; manufactured material; medication; monograph; pediatric; reference standards

Online: 8 March 2022 (08:24:35 CET)

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Preprint ARTICLE | doi:10.20944/preprints202203.0068.v1

Global DNA Methylation in Cord Blood as a Biomarker for Prenatal Lead and Antimony Exposures

Yoshinori Okamoto, Miyuki Iwai-Shimada, Kunihiko Nakai, Nozomi Tatsuta, Yoko Mori, Akira Aoki, Nakao Kojima, Tatsuyuki Takada, Hiroshi Satoh, Hideto Jinno

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: global DNA methylation; global DNA hydroxymethylation; cord blood DNA; lead; antimony; birth cohort

Online: 3 March 2022 (15:04:56 CET)

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Preprint ARTICLE | doi:10.20944/preprints202203.0063.v1

Dioscin-mediated Autophagy Alleviates Neuronal Degeneration in MPP+-treated SH-SY5Y of Parkinson's Disease Model

Shofiul Azam, Md Ezazul Haque, Duk-Yeon Cho, Joon-Soo Kim, Md. Jakaria, In-Su Kim, Dong-Kug Choi

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: MPP+; neurotoxicity; autophagy; apoptosis; neuroprotection; Parkinson's disease

Online: 3 March 2022 (10:36:29 CET)

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Preprint REVIEW | doi:10.20944/preprints202202.0313.v2

The Role of Seawater and Saline Solutions in Treatment of Respiratory Conditions

Danijela Štanfel, Livije Kalogjera, Sergej V. Ryazantsev, Kristina Hlača, Elena Y. Radtsig, Rashidov Teimuraz, Pero Hrabač, Vasyl I. Popovich

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: seawater, seawater preparation, Aqua Maris, nasal irrigation, upper respiratory track, otorhinolaryngology

Online: 1 March 2022 (07:32:11 CET)

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Preprint ARTICLE | doi:10.20944/preprints202202.0349.v1

Identification of Novel Direct Small-Molecule Inhibitors against HIF-2A using Structure-based Virtual Screening and Molecular Dynamics Simulation

Behnaz Yazdani, Peter A.C. Wing, Francisco J. Enguita, Hajar Sirous

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Hypoxia-inducible factor; cancer; hypoxia; drug discovery; medicinal chemistry; virtual screening; molecular dynamics simulation; MM-PBSA; Drug discovery

Online: 28 February 2022 (08:40:24 CET)

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Preprint ARTICLE | doi:10.20944/preprints202202.0327.v1

Experiences and Perspectives of Marketing Authorisation Holders Towards the Monitoring of Medication Safety during Pregnancy: A Qualitative Analysis on a Pan-European Level

Laure Sillis, Veerle Foulon, Jan Y. Verbakel, Michael Ceulemans

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: pregnancy; medicines; drug information; drug safety; pharmacovigilance; pharmacoepidemiology; pharmaceutical industry; stakeholders

Online: 25 February 2022 (08:54:01 CET)

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Preprint REVIEW | doi:10.20944/preprints202202.0313.v1

The Role of Seawater and Saline Solutions in Treatment of Respiratory Conditions

Danijela Štanfel, Livije Kalogjera, Sergej V. Ryazantsev, Kristina Hlača, Elena Y. Radtsig, Rashidov Teimuraz, Pero Hrabač, Vasyl I. Popovich

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: seawater; seawater preparation; Aqua Maris; nasal irrigation; upper respiratory track; otorhinolaryngology

Online: 24 February 2022 (11:01:41 CET)

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Preprint ARTICLE | doi:10.20944/preprints202202.0132.v1

Differential Acellular Reactive Oxygen Species (ROS) Generation by E-cigarettes Containing Tobacco-Free Nicotine (TFN) and Tobacco-Derived Nicotine

Shaiesh Yogeswaran, Irfan Rahman

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Tobacco Free Nicotine (TFN); Synthetic Nicotine; Tobacco-derived Nicotine; vape-bar; Electronic Nicotine Delivery Systems; Reactive Oxygen Species (ROS)

Online: 9 February 2022 (10:37:28 CET)

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Preprint ARTICLE | doi:10.20944/preprints202202.0107.v1

Virtual Screening of Selected Phytochemicals From Four Antimalarial Plants Predicted Potential Inhibitors of Wild Type and Mutant Forms of Dihydrofolate Reductase-Thymidylate Synthase in Plasmodium sp.

Moses Ikegbunam, InnocentMary Ejiofor, Vincent Duru, Amarachi Akachukwu, Emmanual Oranu, Jude Nnaemeka Okoyeh, Samuel Egieyeh

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Malaria; Resistance; Mutation; Virtual screening; Phytochemicals; Dihydrofolate Reductase –Tymidylate Synthase

Online: 8 February 2022 (12:06:36 CET)

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Preprint ARTICLE | doi:10.20944/preprints202202.0091.v1

The Effect of Avocado Seed Extract (Persea americana) on Carbide Induced Hepatoxicity in Adult Wistar Rats

Victoria Nneoma Okpala, Mark Matthew Edet, Damian Nnabuihe Ezejindu

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Avocado; Calcium carbide; hepatotoxicity; liver; Persea Americana; seed extract; toxicity; wistar rats.

Online: 7 February 2022 (13:22:28 CET)

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Preprint ARTICLE | doi:10.20944/preprints202201.0472.v1

Prediction of Low-Dose Aspirin-Induced Gastric Toxicity Using Nuclear Magnetic Resonance Spectroscopy-Based Pharmacometabolomics in Rats

Abubakar Sha'aban, Hadzliana Zainal, Nor Azlina Khalil, Fatimatuzzahra' Abd Aziz, Ewe Seng Ch'ng, Chin‑Hoe Teh, Mustapha Mohammed, Baharudin Ibrahim

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: aspirin; pharmacometabolomic; nuclear magnetic resonance; spectroscopy; gastric toxicity; multivariate analysis

Online: 31 January 2022 (17:26:48 CET)

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Preprint ARTICLE | doi:10.20944/preprints202201.0456.v1

Do The Polymeric Nanoparticles Really Enhance The Bioavailability Of Oral Drugs? A Quantitative Answer Using Meta-analysis

Rania Mohammed Hathout

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: oral; drugs; nanoparticles; polymers; systematic; meta-analysis

Online: 31 January 2022 (12:47:01 CET)

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Preprint REVIEW | doi:10.20944/preprints202201.0453.v1

Potential of Methocinnamox to Treat Opioid Misuse

Colleen Jordan, Amy Kennalley, Tenzing Dolma, Kaitlyn Nemes, Alivia Roberts, Brian Piper

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: methocinnamox; opioid; naloxone; naltrexone; methadone; buprenorphine; overdose; treatment; receptors; addiction

Online: 31 January 2022 (11:48:27 CET)

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Preprint REVIEW | doi:10.20944/preprints202201.0277.v1

Potential Clinical Benefits of TDM of Antimicrobials in Japan

Fumiya Ebihara, Yukihiro Hamada, Takumi Maruyama, Toshimi Kimura

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: HPLC; TDM; ceftriaxone; daptomycin; linezolid

Online: 19 January 2022 (14:29:36 CET)

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Preprint REVIEW | doi:10.20944/preprints202201.0064.v1

Study Designs for Evaluation of Combination Treatment: Focus On Individual Patient Benefit

Martin C. Michel, David Staskin

Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: combination treatment; monotherapy; clinical trial design; benefit/risk assessment

Online: 6 January 2022 (10:14:10 CET)

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MEDICINE & PHARMACOLOGY