Chemical synthesis of super messenger RNA medicine.

Messenger RNAmRNAmedicine was urgently approved in 2020 as a vaccine for COVID-19 . However, current mRNA therapeutics are not fully established, with challenges remaining in translation efficiency and drug delivery system. Therefore, further research is needed to adapt mRNA therapeutics to other diseases. Furthermore, the preparation of mRNA drugs is time-consuming and costly because of the biological methods used. Our laboratory has been working on chemical methods to solve these issues. In this paper, we introduce chemical modifications and novel capping reactions as a method to improve the translation efficiency of mRNA and the introduction of disulfide modification to oligonucleotide therapeutics as an effort on the drug delivery system.Copyright © 2023, Japan Society of Drug Delivery System. All rights reserved.

Nanosponges: As a Dynamic Drug Delivery Approach for Targeted Delivery

Recent advancements in nanotechnology have resulted in improved medicine delivery to the target site. Nanosponges are three-dimensional drug delivery systems that are nanoscale in size and created by cross-linking polymers. The introduction of Nanosponges has been a significant step toward overcoming issues such as drug toxicity, low bioavailability, and predictable medication release. Using a new way of nanotechnology, nanosponges, which are porous with small sponges (below one microm) flowing throughout the body, have demonstrated excellent results in delivering drugs. As a result, they reach the target place, attach to the skin's surface, and slowly release the medicine. Nanosponges can be used to encapsulate a wide range of medicines, including both hydrophilic and lipophilic pharmaceuticals. The medication delivery method using nanosponges is one of the most promising fields in pharmacy. It can be used as a biocatalyst carrier for vaccines, antibodies, enzymes, and proteins to be released. The existing study enlightens on the preparation method, evaluation, and prospective application in a medication delivery system and also focuses on patents filed in the field of nanosponges.Copyright © 2023 The Authors.

Current status and hotspot of Lonicera Japonica Flos research based on bibliometrics.

In order to comprehensively understand the research hotspots and development trends of Lonicera Japonica Flos in the past 20 years, and to provide intuitive data reference and objective opinions and suggestions for subsequent related research in this field, this study collected 8 871 Chinese literature and 311 English literature related to Lonicera Japonica Flos research in the core collection databases of Wanfang Data), CNKI and Web of Science (WOS) from 2002 to 2021, and conducted bibliometric and visual analysis using vosviewer. The results showed that the research on the active components of Lonicera Japonica Flos based on phenolic acid components, the research on the mechanism of novel coronavirus pneumonia based on data mining and molecular docking technology, and the pharmacological research on the anti-inflammatory and antiviral properties of Lonicera Japonica Flos are the three hot research directions in the may become the future research direction. In this paper, we analyze the research on Lonicera Japonica Flos from five aspects: active ingredients, research methods, formulation and preparation, pharmacological effects and clinical applications, aiming to reveal the research hotspots, frontiers and development trends in this field and provide predictions and references for future research.Copyright © Drug Evaluation Research 2022.

Synthesis and evaluation of imidazole-bearing chalcones as a potential treatment for pulmonary aspergillosis

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.

Assembling a structural model of the SARS-CoV-2 replication and transcription complex from 60+ subunits

The SARS-CoV-2 replication and transcription complex (RTC) is made up of nine distinct non-structural viral proteins encoded by the ORF1ab gene. These proteins house seven enzymatic sites that synthesize new viral genomic and subgenomic RNA, proofread and correct errors in the synthesis, add a 5'-cap to the nascent RNA, and truncate the intermediate negative sense 5'-poly-U tail. While x-ray crystallography and cryo-EM have provided high resolution structures of each of the individual proteins of the RTC and have shed light on how subsets of the proteins associate, a full picture of the RTC has remained elusive. Using molecular modeling tools, including protein-protein docking, we have generated a model of the RTC centered around hexameric nsp15, which is capped on two faces by trimers of nsp14/nsp16/(nsp10)2. A conformational change of nsp14, necessary to facilitate binding to nsp15, then recruits six nsp12/nsp7/(nsp8)2 polymerase subunits. To this, six nsp13 subunits are distributed around the complex. The resulting superstructure is composed of 60 subunits total and positions the nsp14 exonuclease and nsp15 endonuclease sites in line with the dsRNA exiting the nsp12 polymerase site. Nsp10 acts to separate the RNA strands, directing the nascent strand to the nsp12 NiRAN site, where a transiently associated nsp9 facilitates the first step in mRNA capping. The RNA is then directed to the nsp14 N7-methyltransferase site and the nsp16 2'O-methyltransferase site to complete the capping. Additionally, template switching during transcription is proposed to be facilitated by positioning of the TRS-L RNA-bound N-protein above the polymerase active site, between two subunits of nsp13. The model, while constructed based on structural considerations, offers a unifying set of hypotheses to explain the diverse set of processes involved in coronavirus genome replication and transcription. All work presented was funded by Gilead Sciences.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Medicines management of long-term conditions during the COVID19 pandemic: a narrative systematic review

Introduction: Due to lockdown measures associated with the COVID 19 pandemic (1), there were substantial changes to healthcare delivery, including the suspension of face-to-face medical appointments, expansion of telehealth and changes to medication protocols.(2) It is important to learn from the successes and challenges of this period to ensure we adapt and improve how we support people to take medicines in the future. Aim(s): We sought to conduct a systematic review to explore the different approaches used to deliver medicines management services for people living with long term conditions (LTCs) during the pandemic and identify strategies that could be integrated into standard care. Method(s): We conducted a systematic review across 3 large databases: MEDLINE (OVID), EMBASE (OVID) and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Our research question and search strategy was developed using the PICO framework (Population: adults with LTCs, Intervention: medicines management during the COVID 19 pandemic;no comparison group. Outcome(s): any aspect relating to medicines management. Search terms relating to 'long term conditions', 'medication management' and 'COVID-19' were used. One reviewer (LM) screened all titles, s, and full texts. We included studies discussing medication management of LTCs, in patients of all ages and healthcare settings, throughout the pandemic. Primary literature sources, feasibility studies and case studies, were included. We excluded studies solely focusing on disease monitoring, or the treatment of COVID/ 'long Covid'. One reviewer performed a thematic analysis, synthesising the findings into themes and sub-themes, which were discussed with a further reviewer (CT). A critical appraisal was performed using the Critical Appraisal Skills Programme checklists. Result(s): The search returned 2365 results. After deduplication, articles were removed at the title (n=1070) (n=813) and full text (n=232) stages. 31 studies were included. Studies were conducted in India (n=6), US (n=5), international (n=4), France (n=2), Italy (n=2), and one each from China, Japan, Jordan, Mexico, Morocco, Nigeria, Romania, Saudi Arabia, Spain, UK, UK and US, and location not specified. Most studies (n=17) employed subjective methods of data collection (surveys/ questionnaires). We identified 6 themes. These were: changes in consultation type, for instance using teleconsultations and smartphone apps to monitor glucose control and diabetic management. Studies described temporary changes to treatment protocols e.g., using oral chemotherapy to reduce the need for in-person appointments and reduce the infection risk associated with intravenous administration. Control of certain conditions for example epilepsy was reduced in some studies. Patients missed doses due to drug shortages associated with disruptions in the medication supply chain, particularly in low-income countries. Finally, we identified prescribing trend changes in certain classes of medicines (e.g. reduced biologic usage due to immunosuppression risk) and an increase in patients self-medicating conditions including anxiety and depression, with associated safety risks. Conclusion(s): This review suggested that certain medical conditions such as diabetes and hypertension were more suited to remote monitoring with technological interventions such as smartphone apps. While other conditions e.g., cancer and epilepsy, demonstrated a greater need for in-person care. Countries of lower socioeconomic status were disproportionately affected by the pandemic.

Medicinal bismuth: Bismuth-organic frameworks as pharmaceutically privileged compounds

Historically organometallic compounds have been used to cure certain diseases with limited applications. Although bismuth belongs to the category of heavy metals, many of its derivatives have found applications in modern drug discovery research, mainly because of its low toxicity and higher bioavailability. Being an eco-friendly mild Lewis acid, compounds having bismuth as a central atom are capable of binding several proteins in humans and other species. Bismuth complexes demonstrated antibacterial potential in syphilis, diarrhea, gastritis, and colitis. Apart from antibacterial activities, bismuth compounds exhibited anticancer, antileishmanial, and some extent of antifungal and other medicinal properties. This article discusses major synthetic methods and pharmacological potentials of bismuth complexes exhibiting in vitro activity to significant clinical performance in a systematic and timely manner.Copyright © 2022 Elsevier Ltd

Synthesis of new 3-(4-methyl-2-arylthiazol-5-yl)-5-aryl-1,2,4-oxadiazole derivatives as potential cytotoxic and antimicrobial agents

Globally cancer is the second leading cause of death;a drug that can cure cancer with the utmost negligible side effects is still a distant goal. Due to increasing antibiotic resistance, microbial infection remains a grave global health security threat. The ongoing coronavirus pandemic increased the risk of microbial and fungal infection. A new series of 3-(4-methyl-2-arylthiazol-5-yl)-5-aryl-1,2,4-oxadiazole (7a-t) have been synthesized. The structure of synthesized compounds was confirmed by the spectrometric analysis. The newly synthesized compounds were screened for cytotoxic activity against breast cell lines MCF-7 and MDA-MB-231. Against the MCF-7 cell line compounds 7f, 7 g and 7n showed excellent activity with GI50 0.6 muM to <100 nM concentration. Compound 7b showed good activity against MDA-MB-231 cell line with GI50 47 muM. The active derivatives 7b, 7e, 7f, 7 g and 7n were further evaluated for cytotoxicity against the epithelial cell line derived from the human embryonic kidney (HEK 293) and were found nontoxic. The thiazolyl-1,2,4-oxadiazole derivatives were also screened to evaluate theirs in vitro antimicrobial potential against Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388), Bacillus subtilis (NCIM 2063), Staphylococcus albus (NCIM 2178), Candida albicans (NCIM 3100) and Aspergillus niger (ATCC 504). Amongst the 7a-t derivatives, six compounds 7a, 7d, 7f, 7n, 7o, 7r showed good antifungal activity against C. albicans and eight compounds 7c, 7d, 7 g, 7h, 7i, 7k, 7l and 7o showed good activity against A. niger. The potential cytotoxic and antifungal activity suggested that the thiazolyl-1,2,4-oxadiazole derivatives could assist in the development of lead compounds for the treatment of cancer and microbial infections.Copyright © 2022 The Authors

A new short synthesis route for favipiravir and its analogue: Their tautomerization behaviour

The study of tautomerism in biologically relevant heterocycles is essential, as it directly affects their chemical properties and biological function. Lactam-lactim tautomerization in pyridine/pyrazine derivatives is such a phenomenon. Favipiravir, a pyrazine derivative, is an essential antiviral drug molecule having notable performance against SARS-CoV-2. Along with a better yielding synthetic method for favipiravir, we have also investigated the lactam-lactim tautomerization of favipiravir and its analogous molecules. Most of these molecules were crystalized and studied for various interactions in their lattice. Many interesting supramolecular interactions such as hydrogen bonding, pi-pi stacking and halogen bonding were revealed during the analysis. Some of these structures show interesting F-F halogen bonding and water channels in their solid state.Copyright © 2022 The Royal Society of Chemistry.

The Emergence of Novel Coronavirus Disease, Global Treatment Update and its Containment Strategies in Overpopulated Countries: A Review

The ongoing pandemic of the novel coronavirus SARS-CoV-2 (COVID-19) has created a major challenge for the public health worldwide. The reported cases indicate that the outbreak is more widespread than initially assumed. Around 18 million people have been infected with 689,000 reported deaths (August 2020;the number is increasing daily);with a high mutation rate, this virus poses an even more serious threat worldwide. The actual source of COVID-19 is still un-clear;even if the initial reports link it to the Chinese seafood wet market in Wuhan, other animals such as birds, snakes, and many small mammals including bats are also linked with this novel coro-navirus. The structure of the COVID-19 shows distinctive proteins among which spike proteins have a pivotal role in host cell attachment and virus-cell membrane fusion in order to facilitate virus infection. Currently, no specific antiviral treatment or vaccine is available. Various drug can-didates, including SARS-CoV and MERS-CoV protease inhibitors, neuraminidase inhibitors, RNA synthesis inhibitors, ACE2 inhibitors and lungs supportive therapy, are under trials. Cell-based therapy also appeared with remarkable treatment possibilities. In this article, we endeavored to succinctly cover the current and available treatment options, including pharmaceuticals, cell-based therapy, and traditional medicine. We also focused on the extent of damages by this novel coron-avirus in India, Pakistan, and Bangladesh;the strategies adopted and the research activities initiat-ed so far by these densely populated countries (neighboring China) are explained in this review.Copyright © 2021 Bentham Science Publishers.

Remdesivir (GS-5734) for COVID-19 Treatment: Past and Recent Updates

Background: SARS-CoV-2 is a pandemic now, and several measures have been taken by countries to prevent, control, and treat the disease. WHO has been working meticulously and has been providing up to date information and statistics on incidences and death. Several broad--spectrum anti-viral drugs are available and have been used in the past to fight against the viral out-break. Recently remdesivir, an experimental prodrug from Gilead Sciences, has been found to be a potential drug to be used as a therapy to treat COVID-19. Objective(s): Here, we have reviewed several previous findings from the literature and present an up to date information on remdesivir. Result(s): Remdesivir was initially invented for use against Ebola virus treatment and has proved ef-fective against different strains of Ebola, Nipah, and other strains of coronaviruses. Clinical trials with remdesivir for COVID-19 patients have begun, and several off label use of remdesivir have been reported recently. Currently, the drug seems to have an effect against the SARS-CoV-2 virus, with side effects among a few patients. Although the results are not conclusive, they are partly promising. This review provides past and recent updates on the use of remdesivir. Conclusion(s): From the review, we conclude that the drug remdesivir is known to exhibit its mechanism of action by terminating the RNA synthesis, and it is a potential drug against the novel coron-avirus.Copyright © 2021 Bentham Science Publishers.

Abstracts of the 26th Annual Meeting of ESPACOMP, the International Society for Medication Adherence

The proceedings contain 88 papers. The topics discussed include: scalability of effective adherence interventions for patients using cardiovascular disease medication: a realist synthesis-inspired systematic review;the presence of medication adherence management courses in European nurse education;from adherence to treatment to adherence to follow-up: paradigm shift of gene therapy for hemophilia;12-year evolution of immunosuppressant non-adherence in adult kidney transplantation recipients: the Swiss transplant cohort study;acceptance and adherence to covid-19vaccine in a Portuguese population survey: role of cognitive and emotional representations;patients' perspectives and experiences of medication use in osteoporosis: systematic review of qualitative studies;patients' perspectives on inflammatory bowel disease medication adherence in southern New Zealand;and determinants of daily HIV pre-exposure prophylaxis implementation among men who have sex with men.

Investigating novel thiazolyl-indazole derivatives as scaffolds for SARS-CoV-2 MPro inhibitors

COVID-19 is a global pandemic caused by infection with the SARS-CoV-2 virus. Remdesivir, a SARS-CoV-2 RNA polymerase inhibitor, is the only drug to have received widespread approval for treatment of COVID-19. The SARS-CoV-2 main protease enzyme (MPro), essential for viral replication and transcription, remains an active target in the search for new treatments. In this study, the ability of novel thiazolyl-indazole derivatives to inhibit MPro is evaluated. These compounds were synthesized via the heterocyclization of phenacyl bromide with (R)-carvone, (R)-pulegone and (R)-menthone thiosemicarbazones. The binding affinity and binding interactions of each compound were evaluated through Schrodinger Glide docking, AMBER molecular dynamics simulations, and MM-GBSA free energy estimation, and these results were compared with similar calculations of MPro binding various 5-mer substrates (VKLQA, VKLQS, VKLQG) and a previously identified MPro tight-binder X77. From these simulations, we can see that binding is driven by residue specific interactions such as pi-stacking with His41, and S/pi interactions with Met49 and Met165. The compounds were also experimentally evaluated in a MPro biochemical assay and the most potent compound containing a phenylthiazole moiety inhibited protease activity with an IC50 of 92.9 muM. This suggests that the phenylthiazole scaffold is a promising candidate for the development of future MPro inhibitors.Copyright © 2022 The Authors

Increasing incidence of Pediatric Graves' Disease

Introduction: Graves' diseases is a rare autoimmune disease in children. Viral infections are considered as a trigger for autoimmune thyroid disorders. A temporal association between SARSCoV- 2 and a novel pediatric hyperinflammatory condition called Paediatric inflammatory multisystem syndrome has been reported in 2020, raising questions about the link between SARS-CoV-2 and autoimmune and autoinflammatory diseases. Over the last year (2021), we noticed an increase in the number of children presenting to our department with Graves' disease. Our primary aim is to document the incidence of Graves' disease in our department since 2005, comparing our data with national data regarding thiamazol delivery. Our secondary aim is to compare the characteristics of the patients diagnosed before and during the SARS-CoV-2 outbreak. Material(s) and Method(s): A retrospective study including all the pediatric patients diagnosed with Graves' disease seen in our department since 2005 was performed. Hyperthyroid newborns were excluded. Data collected were the date and the age at diagnosis, the thyroid hormone levels, TSI at diagnosis, data from the national health insurance regarding the number of delivered thyroid hormone synthesis inhibitor drugs, thiamazol, in children (<18 years)/year. Result(s): A total of 48 patients with Graves' disease were diagnosed since 2005 in our department. Fifteen patients (1/3) were diagnosed since the SARS-CoV-2 outbreak, with the highest incidence in 2021 (11 patients). At the national level, an increase of thiamazol delivery is observed in 2020 and 2021 compared to the preceding years. Similar results regarding the age of diagnosis, free T4 and T3 levels or the presence of auto-immune diseases in the personal or family history were observed between the patients diagnosed before and those diagnosed during the SARS-CoV-2 outbreak. Conclusion(s): We observed a temporal association between SARS-CoV-2 outbreak and an increase in pediatric Graves' disease. The age and severity of the disease seems not to be influenced by the SARS-CoV-2 outbreak. SARS-CoV-2 could thus constitute a trigger for pediatric Graves' disease. Further studies are needed to confirm our findings.

Highly Efficient Base-Catalyzed Synthesisof Piperidine-4-Imine Lead Molecules for SARS-Cov-2 Mutant Spike Proteasevia in Silico Method

For the discovery of drugs to SARS-CoV-2 pandemics, we have developed a new series of piperidine-4-imines as the central core owing to significant pharmaceuticaldemands on it. The synthesis of piperidine-4-imines involvesatwo-step base-catalyzed reaction, namely (i)condensations followed by cyclization with aromatic aldehyde, aliphatic ketone, and ammonia to yield piperidine-4-ketone core, and (ii) a simple Schiff base/piperidine-4-imines formation between piperidine-4-ketone andvarious aromatic primary amines. All the synthesized intermediate and target piperidine-4-imines molecular structures were well characterized by NMR, FT-IR, and mass spectral studies. Further, the ground state geometry of synthesized molecules was optimized using density function theory (DFT) with basis set of b3lyp 6-31g (d,p) in Gaussian 09 program. Using this molecular geometry, we docked against SARS-CoV-2 mutant spike protease of delta, delta plus, and omicron, which shows an effective binding ability. In addition, Lipinski's rule, pre ADME and toxicity studies also reveal drug-likeness properties. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Advancements and Future Perspectives of 1, 2, 3 Triazole Scaffold as Promising Antiviral Agent in Drug Discovery

Severe viral infections like Covid-19 are emerging now a day and are the common causes of human illness and death. Presently, we have a limited availability of antiviral chemotherapeutic agents to prevent and treat these infections, so it is the need of an hour to develop potential antiviral drugs against various harmful and fatal viral infections. A large quantity of research has been performed on 1, 2, 3 triazole and their derivatives, which has proved the promising antiviral activity of this heterocyclic nucleus. Among nitrogen-containing heterocyclic compounds, 1, 2, 3-triazoles are privileged structure motifs and received great attention in academics and industry. Even though absent in nature, 1, 2, 3-triazoles have found broad applications in drug discovery, organic synthesis, polymer chemistry, supramolecular chemistry, bioconjugation, chemical biology, fluorescent imaging, and materials science. 1, 2, 3 triazole nucleus is one of the most important and well-known heterocycle which is a common and integral skeleton of a variety of medicinal compounds like antidepressant, antihistaminic, antioxidant, antitubercular, anti-Parkinson, antineoplastic, antihypertensive, antimalarial, local anaesthetic, antianxiety, antiobesity and immunomodulatory agents, etc. 1, 2, 3 triazole emerged as a pharmacologically significant scaffolds due to its broad and potent activity against severe infections. This review primarily lays emphasis on the recent advancements in the synthesis and biological evaluation of 1, 2, 3 triazole derivatives as antiviral agents which may facilitate the development of more potent and effective antiviral agents. Copyright © 2022 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.

A CASE OF LOMUSTINE-INDUCED PNEUMONITIS

SESSION TITLE: Drug-Induced Lung Injury and Disease SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Lomustine, a nitrosurea, inhibits DNA, RNA, and protein synthesis by carbamylation and alkylation, leading to cytotoxic effects 1, 3. Its concentration is high in the central nervous system (CNS) and therefore is commonly used for the management of CNS tumors including recurrent glioblastoma. While known side effects include pancytopenia, few pulmonary toxicities have been reported. This case is a rare example of lomustine induced pneumonitis. CASE PRESENTATION: A 54-year-old female with a history of glioblastoma, treated with a combination of surgical resection, radiation therapy, and temozolomide followed by stereotactic surgery and bevacizumab after disease recurrence, developed progressive dyspnea after initiating lomustine. She had received one dose of lomustine 90 mg/m2 two months prior to developing dyspnea upon exertion. At baseline, she was an active individual who played sports. A chest computed tomography (CT) scan preformed ten months prior was without any parenchymal abnormalities, and pulmonary function tests (PFTs) two months prior were normal with an adjusted DLCO of 15.4 mL/mmHg/min (88%). Repeat chest CT revealed diffuse ground glass opacities, and repeat PFTs showed a moderately impaired adjusted DLCO of 10.4 mL/mmHg/min (60%). Other lab evaluation, CBC, BNP, troponin, and COVID PCR, were negative. After receiving six weeks of steroids, there was resolution of CT findings, improvement of DLCO, and relief from symptoms. DISCUSSION: More common adverse effects of lomustine are GI discomfort and pancytopenia. It is less widely documented to cause pulmonary toxicity compared to its chemical relative carmustine 1, 3. This is perhaps due to decreased alkylation ability and penetration into the lung tissue by lomustine7. There have been few case reports revealing pneumonitis and pulmonary fibrosis. Lomustine induced pneumonitis induces acute parenchymal changes of the lung demonstrated by characteristic symptoms and imaging/biopsies abnormalities after initiation of a drug. 2 Findings include breathlessness, dyspnea upon exertion, cough, hypoxia, crackles upon lung auscultation. PFT's may show a restrictive pattern with decreased FEV1/FVC ratio and DLCO. Imaging may reveal diffuse groundglass opacities, traction bronchiectasis, interlobular septal thickening, and honeycombing. Bronchoscopy with lavage would rule out infection. Management involves discontinuation of culprit medication, immunosuppression, and supportive therapies to alleviate respiratory discomfort. Lack of treatment may produce complications of acute respiratory distress syndrome and fibrosis. CONCLUSIONS: Lomustine is an essential treatment drug for recurrent CNS tumors. Toxicities such as pneumonitis have been rarely demonstrated. Timely recognition of pneumonitis features is key to treat this complication, improve quality of life, and prevent permanent lung compromise. Reference #1: Dent RG. Fatal pulmonary toxic effects of lomustine. British medical journal. 1982;DOI:10.1136/thx.37.8.627 Reference #2: Skeoch S, Weatherley N, Swift AJ, Oldroyd A, Johns C, Hayton, C, et al. Drug-Induced Interstitial Lung Disease: A Systemic Review. Journal of Clinical Medicine. 2018;doi 10.3390/jcm7100356 Reference #3: Weiss RB, Issell BF. The nitrosureas: carmustine and lomustine. Cancer treatment reviews. 1982;https://doi.org/10.1016/S0305-7372(82)80043-1 DISCLOSURES: No relevant relationships by Sukhdeep Kaur No relevant relationships by Chelsea Kennedy-Snodgrass No relevant relationships by Sarun Thomas

EFFECTS OF SLEEP RESTRICTION AND RECOVERY ON THE CAPACITY OF GLUCOCORTICOIDS TO INHIBIT INFLAMMATORY MARKER EXPRESSION IN HUMAN MONOCYTES

Introduction: Chronic low-grade systemic inflammation is involved in the pathogenesis of many human diseases. Common sleep patterns of restricting sleep during weekdays and catching up on sleep over the weekend induce inflammatory upregulation that may not resolve following weekend recovery sleep. We hypothesize that this sleep pattern leads to an inflammatory imbalance of markers regulating inflammatory homeostasis, including inflammatory markers (eg, interleukin-6 (IL-6) and cyclooxygenase 2 (COX-2)) and markers of counter-inflammation (eg, glucocorticoids (GCs)). The enzyme COX-2 is involved in prostaglandin synthesis and is the target of pain-relieving nonsteroidal anti-inflammatory drugs (NSAIDs). GCs are used in the treatment of many inflammatory diseases, including severe acute infection with SARS-CoV-2. We investigated if sleep restriction impairs the capacity of GCs to inhibit inflammatory COX-2 expression in a preliminary dataset. Methods: The present preliminary dataset (N=6, 2F/4M) derives from an ongoing randomized controlled within-subjects trial consisting of three 11-day in-hospital protocols (2 restricted sleep arms, 1 control sleep arm). The ongoing study is blinded for administration of placebo or aspirin under sleep restriction. Under restricted sleep conditions, 2 nights of baseline sleep (8h/night) were followed by 5 nights of restricted sleep (4h/ night), concluding with 3 nights of recovery sleep (8h/night). In the control condition, participants could sleep 8h/night throughout the entire protocol. Blood samples were taken after baseline sleep, after 5 nights of restricted or control sleep, and after 2 nights of recovery sleep. Data were analyzed using generalized linear mixed models. Results: Sleep restriction was associated with decreased capacity of GCs to inhibit COX-2 expression in monocytes (p<.01) and has the expected inflammatory effect on IL-6 production in monocytes (p<.01). Moreover, sleep restriction has lasting inflammatory effects as shown in increased inflammation following 2 nights of recovery sleep (p<.01). Conclusion: In conclusion, the present preliminary analysis suggests that in patients treated with GCs, sleep restriction potentially reduces their effectiveness in controlling inflammation, thus contributing to increased inflammation-related morbidity. Sample collection and data analysis is ongoing.