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Remdesivir (RDV) is an antiviral medication used most recently for the treatment of COVID-19. Although no adverse effects were observed on perinatal parameters in reproductive and development toxicology studies at doses up to four-fold clinical area under the curve (AUC) exposures, some researchers have reported that therapeutic levels of RDV may impair early embryogenesis, as observed by in vitro studies. In addition, the influence of prenatal RDV exposure on maternal IgG transfer in the placenta is still unknown. Administration of RDV in pregnant humanized mouse model (Tg32), which expresses the human Fc gamma receptor and transporter (FCGRT) gene, was used to further evaluate potential effects on IgG transfer and concurrent perinatal endpoints. Animals were dosed daily from gestational days (GDs) 10- 14 with 25 mg/kg RDV (GS-5734) via intravenous injection (n=3-5 per group). Concurrent vehicle control animals were dosed intravenously with 12% sulfobutyl ether- beta-cyclodextrin in water (pH3.5;NaOH/HCl). All animals were administered 2 mg/kg human IgG via intravenous injection on GD 14. Placentae and fetuses were collected from dams on GD 14, 15, 16, and 18 and evaluated using histopathology and qPCR for inflammation markers. No abnormal morphologies (necrosis/apoptosis) of placentae were observed between the concurrent control and RDVdosed groups. Additionally, no differences in maternal body weights were observed. There were no statistically significant differences in placenta weights. There were no statistically significant changes in pregnancy parameters (implantation sites and dead fetuses/litter) and fetal weights between the RDV-dosed group and concurrent controls at GD 14, 15, 16, and 18. No changes were observed in transcript levels of inflammation markers in the RDV-dosed group when compared to the concurrent control group. There was a slightly lower ratio of fetal IgG level to maternal IgG levels in the RDV-dosed group;however, no statistically significant differences were observed between the RDV-dosed group and concurrent controls on GD 14, 15, 16, and 18. Our results suggest that a daily dose of 25 mg/kg RDV on GDs 10-14 in humanized mice did not cause adverse effects on placenta and fetal development. (Funded by the Perinatal Health Center of Excellence: E0300201.).
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Pulmonary aspergillosis (PA) is a category of respiratory illnesses that significantly impacts the lives of immunocompromised individuals. However, new classifications of secondary infections like influenza associated aspergillosis (IAA) and COVID-19 associated pulmonary aspergillosis (CAPA) only exacerbate matters by expanding the demographic beyond the immunocompromised. Meanwhile anti-fungal resistant strains of Aspergillus are causing current treatments to act less effectively. Symptoms can range from mild (difficulty breathing, and expectoration of blood) to severe (multi organ failure, and neurological disease). Millions are affected yearly, and mortality rates range from 20-90% making it imperative to develop novel medicines to curtail this evolving group of diseases. Chalcones and imidazoles are current antifungal pharmacophores used to treat PA. Chalcones are a group of plant-derived flavonoids that have a variety of pharmacological effects, such as, antibacterial, anticancer, antimicrobial, and anti-inflammatory activities. Imidazoles are another class of drug that possess antibacterial, antiprotozoal, and anthelmintic activities. The increase in antifungal resistant Aspergillus and Candida species make it imperative for us to synthesize novel pharmacophores for therapeutic use. Our objective was to synthesize a chalcone and imidazole into a single pharmacophore and to evaluate its effectiveness against three different fungi from the Aspergillus or Candida species. The chalcones were synthesized via the Claisen-Schmidt aldol condensation of 4-(1H-Imizadol-1-yl) benzaldehyde with various substituted acetophenones using aqueous sodium hydroxide in methanol. The anti-fungal activity of the synthesized chalcones were evaluated via a welldiffusion assay against Aspergillus fumigatus, Aspergillus niger, and Candida albicans. The data obtained suggests that chalcone derivatives with electron-withdrawing substituents are moderately effective against Aspergillus and has the potential for further optimization as a treatment for pulmonary aspergillosis. This project was supported by grants from the National Institutes of Health (NIH), National Institute of General Medicine Sciences (NIGMS), IDeA Networks of Biomedical Research Excellence (INBRE), Award number: P20GM103466. The content is solely the responsibility of the authors and do not necessarily represent the official views of the NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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SESSION TITLE: Occupational and Environmental Lung Disease Cases SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Sodium hydroxide and ammonium salt vapor exposure are known to cause epithelial necrosis of the tracheobronchial tree, but no pathologic descriptions exist of subsequent inflammatory pneumonitis. CASE PRESENTATION: A 56-year-old man presented to the outpatient clinic with 2 months of progressive scant hemoptysis and dyspnea on exertion. He had a mild smoking history, a history of longstanding stable UC, and had a history significant only for recently performing multiple weeks of cleaning work on a large, enclosed HVAC system with chemicals containing sodium hydroxide and ammonium. He wore no respiratory protection at work. CXR was significant for streaky bilateral lower lobe opacities and CT Chest revealed bilateral basilar ground-glass opacities with a small left pneumothorax. His PFT demonstrated mild restriction with a diffusion defect. Infiltrates persisted after treatment with levofloxacin. A broad autoimmune panel was normal. Bronchoscopy with cryobiopsy showed organizing pneumonia with foreign body reaction. BAL showed primarily mast cells and no organisms were found. Prednisone at 60mg daily with Bactrim prophylaxis and a subsequent prolonged wean was initiated with marked improvement. DISCUSSION: Industrial HVAC cleaning agents are widely used with the proliferation of HVAC systems in the post-COVID world. Other examples exist of prolonged cleaning product use and lung function decline (Svanes et al). Our case report hypothesizes a link between inhalational exposure to sodium hydroxide and ammonium salts with organizing pneumonia with foreign body features, a previously unknown effect. Prednisone led to improvement. CONCLUSIONS: High suspicion for occult pneumonitis should exist when patients present with prolonged exposure to cleaning/noxious chemical vapors exist. Respiratory protection should be emphasized as a public health policy to prevent lung damage among any type of cleaner use including high-skilled (HVAC) cleaners. Reference #1: Advenier, A., & Grandmaison, G. (2022). PULMONARY ACUTE LESIONS AFTER CAUSTIC EXPOSURE. Retrieved 31 March 2022, from https://www.lungdiseasesjournal.com/articles/pulmonary-acute-lesions-after-caustic-exposure.html Reference #2: Svanes, Ø., Bertelsen, R. J., Lygre, S., Carsin, A. E., Antó, J. M., Forsberg, B., García-García, J. M., Gullón, J. A., Heinrich, J., Holm, M., Kogevinas, M., Urrutia, I., Leynaert, B., Moratalla, J. M., Le Moual, N., Lytras, T., Norbäck, D., Nowak, D., Olivieri, M., Pin, I., … Svanes, C. (2018). Cleaning at Home and at Work in Relation to Lung Function Decline and Airway Obstruction. American journal of respiratory and critical care medicine, 197(9), 1157–1163. https://doi.org/10.1164/rccm.201706-1311OC Reference #3: Gorguner, M., & Akgun, M. (2010). Acute inhalation injury. The Eurasian journal of medicine, 42(1), 28–35. https://doi.org/10.5152/eajm.2010.09 DISCLOSURES: no disclosure on file for Ai-Yui Maria Tan;No relevant relationships by Sudha Misra No relevant relationships by Amrik Ray
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Soaps are used widely by humans in many aspects. Exclusively, the emergence of the SARS-Cov-2 virus made people wash their hands frequently to disinfect the virus to prevent virus infection. Soaps made of herbals possess constituents that goodness the skin as well to rejuvenate the mind and body factors. Dried leaves of Basil, Neem and Acalypha Indica, Aloe vera, and Hibiscus flower are used here to prepare homemade soap. The steam distillation process is an imperative process by which the oils are used from raw materials like dried leaves for the preparation of soaps. Extracts obtained from the herbal plants are used as additives in the preparation of soap that would be added besides the lye and other constituents. Lye preferred here is Sodium Hydroxide (NaOH) and the cast shapes utilized here in determining the soap shape are Elliptic and Rectangle. pH value, the total fatty matter is determined using respective methodologies, and the materials used in the preparation of soap are estimated using the accessible software called SoapCalc Recipe Calculator. Soaps made using the mentioned ingredients are safe and robust for cleaning the skin and hands.
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This study presents the results of an experimental campaign on the use of municipal solid waste incinerator bottom ash (MIBA) and fly ash (FA) as precursors for the production of alkali-activated materials. MIBA was subjected to a pre-treatment stage in response to two issues: high metallic aluminum content, which reacts in a high pH solution, releasing hydrogen;and low amorphous content of silica-, aluminum- and calcium-bearing phases, which translates into a limited formation of reaction products. The proposed pre-treatment stage oxidizes most of the metallic aluminum fraction and compensates for the low reactivity of the material via the formation of additional reactants. Different combinations of MIBA and FA were tried—mass-based ratios of 0/100, 25/75, 50/50, 75/25, and 100/0 for MIBA/FA. Two mix designs of the alkaline activator with sodium hydroxide and sodium silicate were evaluated by varying the Na2O/binder and SiO2/Na2O ratios. These mortars were tested in the fresh and hardened state. The results showed that the pre-treatment stage was effective at stabilizing the dimensional variation of MIBA. Despite the lower reactivity of MIBA, mortars with 50/50 of MIBA/FA presented a maximum 28-day compressive strength of 25.2 MPa, higher than the 5.7 MPa of mortars made with MIBA only.
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Featured ApplicationThis study shows the use of a by-product from the manufacture of a novel antiseptic/disinfectant (HOCl) to obtain a protein isolate from defatted soybean flour (a co-product from the soybean oil industry);an optimization process was carried out to create an industrial symbiosis.Defatted soybean flour is generated during the oil extraction process of soybean, and it has a protein content of ~50%. On the other hand, an alkaline solution of NaOH is produced during the electrolysis process of NaCl in a novel method used to make a potent disinfectant/antiseptic (HOCl). In the present work, we suggest using these two products to produce soy protein isolate (SPI), aiming to create an industrial symbiosis. A Box–Behnken experimental design was executed, and a surface response analysis was performed to optimize temperature, alkaline solution, and time used for SPI extraction. The SPI produced at optimal conditions was then characterized. The experimental results fit well with a second-order polynomial equation that could predict 93.15% of the variability under a combination of 70 °C, alkaline solution 3 (pH 12.68), and 44.7 min of the process. The model predicts a 49.79% extraction yield, and when tested, we obtained 48.30% within the confidence interval (46.66–52.93%). The obtained SPI was comparable in content and structure with a commercial SPI by molecular weight and molecular spectroscopy characterization. Finally, the urease activity (UA) test was negative, indicating no activity for trypsin inhibitor. Based on the functional properties, the SPI is suitable for food applications.
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Objectives: With over 90 million cases reported in the globe, the COVID-19 pandemic caused by SARS-CoV-2 has been a serious public health crisis. Development of novel and specific antiviral drugs against the SARS-CoV-2 has been an urgent demand. One such drug is Favipiravir, initially developed as an antiviral drug against influenza. Now Favipiravir has received approvals for emergency use against SARS-CoV-2 in many countries. A better understanding of Favipiravir’s biodistribution and pharmacokinetics in vivo will facilitate the clinical development of antiviral drugs against the SARS-CoV-2. Herein, we reported the evaluation of [18 F]Favipiravir with PET in cross-species studies to demonstrate the drug’s biodistribu-tion and pharmacokinetics and investigate the potentially increased risk of neurodegenerative diseases and/or neuroinflammation to COVID-19. Methods: The radiosynthesis of [18 F]Favipiravir was via labeling a commercially available precursor, methyl-5-chloroisoxazolo[4,5-b] pyrazine-3-carboxylate with K[18F]F/K222 and K2CO3 in DMSO at 130°C for 10 min, followed by hydrolysis with NaOH (aq.) at 110°C for 15 min.1 The whole body distribution on CD-1 mice was performed at four time points (5, 15, 30, 60 min). PET studies were carried out in CD-1 mice and AD mice (5XFAD) and naïve rhesus monkeys. We also performed the radiometabolite analysis of [18 F]Favipiravir in plasma and brain of CD-1 mice at 30 min post-injection. Results: [18 F]Favipiravir was obtained in 29% isolated radiochemi-cal yield (decay corrected). The radiochemical purity of the tracer was greater than 99%. No sign of radiolysis was observed for [18F] Favipiravir up to 120 min after formulation with 10% EtOH/saline. High radioactivity accumulation was observed in blood, lung, liver, kidney, and bone (around or more than 5% ID/g, injected dose per gram of wet tissue). The radioactivity level reached a plateau in small intestine, kidney and liver at 30,15 and 5 min, respectively, followed by slow washout, indicating that [18F]Favipiravir was possibly eliminated via the hepatobiliary and urinary pathway. For the radio-metabolic analysis of [18F]Favipiravir, average 41% and 89% of the radioactivity was parent fraction in the mice brain and plasma at 30 min post-injection (n=2), respectively. In PET imaging of CD-1 mice, the standard uptake value (SUV) of [18F]Favipiravir in brain reached its max value of 0.5 at 10 min and slowly reduced to 0.4 at 60 min. The results of PET imaging of AD mice with [18 F]Favipiravir were similar with that of CD-1 mice. In PET imaging of Rhesus monkeys, the brain uptake of [18 F]Favipiravir reached the max value of 0.5 SUV at 5 min and subsequently decreased to 50-60% of the maximum at 60 min. Conclusion: The evaluation of [18F]Favipiravir has demonstrated with bio-distribution and PET in mice and NHPs. Further evaluation of pharmacokinetics of [18F]Favipiravir in whole body monkey scans and LPS-induced neuroinflammation models is underway.
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BACKGROUND: Peronema canescens (Sungkai) leaves have been popular in Indonesia which contain various bioactive compounds with empirical therapeutic efficacy in dealing with COVID-19 and various other diseases. Total phenolic and flavonoid content and antioxidant activity using the DPPH method from P. canescens leaf extract have not been studied much. AIM: This research has several objectives. The first is to compare the results of qualitative phytochemical analysis of the ethanol extract of the leaves of P. canescens (EEPL). The second is to measure the total phenol and flavonoid content. The third is to test the FTIR and antioxidant activity of the ethanol extract of P. canescens leaves in vitro using the DPPH method. METHODS: Fresh plant material and simplicia, ethanol extract extracted by maceration method using 96% ethanol as solvent from P. canescens. The Dragendorff’s and Mayer test carried out the qualitative phytochemical analysis, FeCl3 test, Salkowski method, Liebermann–Burchard method, foam test, and NaOH reagent. The total phenolic and flavonoid levels were tested using the Folin–Ciocalteu method. In vitro antioxidant activity was carried out using the DPPH (1,1-diphenyl-2-picrylhydrazyl) method. RESULTS: The results of qualitative phytochemical screening showed that alkaloids, flavonoids, saponins, tannins, and steroids were detected in the extract of P. canescens. The spectra from the FTIR test results showed various absorbance peak values indicating the bonding of specific functional groups, namely: 418.12, 599.94, 666.67, 1036.39, 1159.52, 1224.16, 1348.95, 1454.19, 1600.87, 1732.00, 2923.13, and 3353.01 cm-1. In the test results, total phenolic content was as much as 5.64% (mgEAG/g) and total flavonoid content of 142,247 mgEQ/g in a sample of 1 mg extract, which was equivalent to 1 mg quercetin. EEPL has antioxidant activity with the DPPH IC50 method of 116.7865 ppm. CONCLUSION: The data obtained at this time can contribute to the exploitation of P. canescens leaves in the future as one of the nutraceutical products, supplements, and herbal medicines by specific industries related to improving the health status of the world community. The higher the bioactive substance in preparation, the more significant the effect of the pharmacological efficacy response. P. canescens ethanol extract has good total phenolic content, total flavonoid content, and antioxidant action.