Chemicals and Drugs Commons^™

Chitosan-Based Hydrogels In Drug Delivery, Salma A. Fereig, Mona Mohamed Ahmed Abdelmottaleb

Pharmacy

Hydrogels are three-dimensional cross-linked hydrophilic polymers that are able to absorb large quantities of water and swell. They have various properties like biocompatibility, low toxicity, and mostly biodegradability, which make them attractive for drug delivery applications. Chitosan hydrogels are especially attractive due to the inherent activities of the chitosan itself like the antibacterial, anti-inflammatory, and tissue regeneration enhancement capacity. Therefore, chitosan hydrogels have been proposed for the delivery of various drugs, genes, cytokines, and stem cells via various routes of administration for the treatment of various diseases as well as different forms of degeneration.

Role Of Protein Kinase A And A Kinase Anchoring Proteins In Buffering And Compartmentation Of Camp Signalling In Human Airway Smooth Muscle Cells, Rinzhin T. Sherpa, Karni S. Moshal, Shailesh R. Agarwal, Rennolds S. Ostrom, Robert D. Harvey

Pharmacy Faculty Articles and Research

Background and Purpose

In human airway smooth muscle (hASM) cells, not all receptors stimulating cAMP production elicit the same effects. This can only be explained if cAMP movement throughout the cell is restricted, yet the mechanisms involved are not fully understood. Phosphodiesterases (PDEs) contribute to compartmentation of many cAMP responses, but PDE activity alone is predicted to be insufficient if cAMP is otherwise freely diffusible. We tested the hypothesis that buffering of cAMP by protein kinase A (PKA) associated with A kinase anchoring proteins (AKAPs) slows cAMP diffusion and that this contributes to receptor-mediated, compartmentalized responses.

Experimental Approach

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Ensemble-Based Mutational Profiling And Network Analysis Of The Sars-Cov-2 Spike Omicron Xbb Lineages For Interactions With The Ace2 Receptor And Antibodies: Cooperation Of Binding Hotspots In Mediating Epistatic Couplings Underlies Binding Mechanism And Immune Escape, Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we performed a computational study of binding mechanisms for the SARS-CoV-2 spike Omicron XBB lineages with the host cell receptor ACE2 and a panel of diverse class one antibodies. The central objective of this investigation was to examine the molecular factors underlying epistatic couplings among convergent evolution hotspots that enable optimal balancing of ACE2 binding and antibody evasion for Omicron variants BA.1, BA2, BA.3, BA.4/BA.5, BQ.1.1, XBB.1, XBB.1.5, and XBB.1.5 + L455F/F456L. By combining evolutionary analysis, molecular dynamics simulations, and ensemble-based mutational scanning of spike protein residues in complexes with ACE2, we identified structural stability and binding …

The Fight For Fluoridation In Stl, Noor Yousaf

Undergraduate Research Symposium

Fluoridation is the addition of fluoride to a source of drinking water. In St. Louis’s public water supply, the amount of fluoride remains the same since 1953 at 5ppm. Dr. Ralph Rosen and his team of dentists and researchers advocated for the fluoridation of the water because it reduced the frequency of dental caries occurring in children and adults alike, but the public had opinions on the sudden addition of chemicals to their water. This includes how the public’s health will be affected, how consumer products would change, and also how effective this addition of fluoride would be. This debate …

Killing Cancer: Manipulating Hydrophobic Vanadium Complexes To Improve Anti-Cancer Activity, Levi Ausherman, Debbie C. Crans, Peter A. Lay, Maggi Braasch-Turi

SACAD: Scholarly Activities

Hydrophobic vanadium complexes have recently shown improved anti-cancer activities compared to cisplatin. The hydrophobicity and anti-proliferative activity of [VO(Hshed)(dtb)] ([Hshed= N-(salicylideneaminato)-N’-(2-hydroxyethyl)-1,2-ethanediamine and dtb= 3,5-di(tert-butyl)catechol)]) have inspired the development of a library of hydrophobic vanadium complexes. Increasing the steric bulk of the catechol ligand has been shown to have a direct impact on hydrophobicity and anti-proliferative activities. Currently at Fort Hays State University, the Braasch-Turi group is synthesizing VO(HSHED)(dtb) to build up material to support the chemical analysis and biological assay performed by our collaborators at Colorado State University and the University of Sydney, Australia, respectively. In the future, we plan …

The Feigned Annoyance And Frustration Test To Activate The Sympathoadrenal Medullary System, Ted W. Gehrig Iii, Lee S. Berk, Robert I. Dudley, Jo A. Smith, Lida Gharibvand, Everett B. Lohman Iii

Physical Therapy Faculty Articles and Research

When perceived as threatening, social interactions have been shown to trigger the sympathoadrenal medullary system as well as the hypothalamic-pituitary-adrenal axis resulting in a physiologic stress response. The allostatic load placed on human health and physiology in the context of acute and chronic stress can have profound health consequences. The purpose of this study was to develop a protocol for a lab-based stress stimulus using social-evaluative threat. While several valid, stress-stimulating protocols exist, we sought to develop one that triggered a physiologic response, did not require significant lab resources, and could be completed in around 10 min. We included 53 …

U.S. Government Agency Podcasts, Bert Chapman

Libraries Faculty and Staff Presentations

Presents podcasts from U.S. Government agencies which can be discovered through the U.S. Government Publishing Office's Catalog of Government Publications. Agencies whose podcasts are presented include the National Institutes of Health, U.S. Peace Corps, U.S. Department of Agriculture, Government Accountability Office (GAO), National Park Service, Department of Justice, Federal Reserve System, and U.S. Naval War College.

Impact Of Fads Genotype On Polyunsaturated Fatty Acid Content In Human Milk Extracellular Vesicles: A Genetic Association Study, John J. Miklavcic, Natalie Paterson, Jennifer Hahn-Holbrook, Laura M. Glynn

Food Science Faculty Articles and Research

Background

Extracellular vesicles in human milk are critical in supporting newborn growth and development. Bioavailability of dietary extracellular vesicles may depend on the composition of membrane lipids. Single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase gene cluster impact the content of long-chain polyunsaturated fatty acids in human milk phospholipids. This study investigated the relation between variation in FADS1 and FADS2 with the content of polyunsaturated fatty acids in extracellular vesicles from human milk.

Methods

Milk was obtained from a cohort of mothers (N = 70) at 2–4 weeks of lactation. SNPs in the FADS gene locus were determined using …

In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2, Kenyon Mitchell, Alfred Amendolara, Ruth Hunter, Jaden Miner, Andrew Payne

Annual Research Symposium

Purpose: Potassium-Chloride Cotransporter 2 (KCC2) is a neuronal membrane protein specific to the central nervous system. It is responsible for removing Cl- ions from the intracellular space, maintaining a normal Cl- gradient essential for proper function at inhibitory synapses. Dysregulation causes an upward shift in the Cl- reversal potential resulting in a hyperexcitable state of the postsynaptic neuron. Existing literature indicates that KCC2 may be involved in the addiction pathway of a variety of drugs of abuse, including opioids and alcohol. This makes KCC2 an attractive potential drug target when treating substance use disorders. A novel direct KCC2 agonist, VU0500469, …

Cold Medicine Abuse And Increased Odds Of Recreational Drug Use, Luis Barco

Posters - 2024

Over the counter (OTC) medications are frequently used to address the symptoms associated with common illnesses that affect the public. (SOURCE) Of these OTC medications, cold and cough medications are some of the most widely used. However, cold medications pose a risk in exhibiting different effects depending on which active ingredient is the most prevalent. Dextromethorphan (DXM), one of the most common ingredients in cough medicine, can lead to the development of symptoms that mirror psychosis associated with phencyclidine abuse (1). Though less common, abuse of codeine can also result in the formation of gastric ulcers, internal bleeding, and inflammation …

Synthesis And Characterization Of Ugi Adducts Of Isatin, Cynthia Domergue, Kimberly Hernandez

Posters - 2024

B-lactam fragments have gathered attention in the chemistry field in being a pharmacophore for medicinal chemistry

- The Ugi reaction involves the reaction of an aldehyde, a primary amine, a carboxylic acid, and an isocyanide to generate α-acetoamido carboxamide derivates (Ugi adducts) -

We focused on the synthesis of the β-lactam derivatives: 1-Benzyl-N-(tert-butyl)-2-oxo-3(2-oxoazetidin-1- yl)indoline-3-carboxamide (4a), N-(tert-Butyl)-2-oxo-3-(2- oxoazetidine-1-yl) indoline-3-carbpxamide (4d) , and N- (tert-Butyl)-1-methyl-2-oxo-3-(2-oxoazetidine-1- yl)indoline-3-carboxamide (4e)

- The Ugi adducts of isatin were synthesized in TFE solvent by stirring the reactant mixture at room temperature and the conversion was monitored by TLC. The solvent was evaporated, and the crude product purified …

Detailing The Effects Of Cannabidiol On Exosome Release In Ewing’S Sarcoma, Bennett Hasley

Theses

Ewing’s sarcoma (ES) is a highly aggressive pediatric cancer found within bone that carries a low five-year survival rate within its patients. This is due, in part, to the cancer’s high malignancy properties as well as the development of resistance to the chemotherapies used to combat this cancer. This project aims to determine if cannabidiol (CBD) has an effect on either exosome release or the protein, signal transducer and activator of transcription 3 (STAT3) within ES cells. Exosomes are vesicles that can carry proteins and other signaling molecules which are released by the cell and allow for cell-to-cell communication. Within …

From Cough To Crip: The Development Of Codeine From A Purely Medical Substance Into A Popular Recreational Drug, Rhett C. Vaughn

Senior Theses

The research that was conducted aimed to elicit the influence that pop culture has on recreational drug consumption. Specifically, the usage of the drug codeine has become very popular in social media among many influencers. The research focuses on the prevalence of this drug across several media platforms, alongside the growing rate of consumption globally. Research was conducted primarily through combining various databases at various organizations and this study aims to compile the data into one coherent paper regarding codeine in pop culture. While, it cannot be solely attributed to one specific outlet or influence, this study found that alongside …

Accurate Characterization Of Binding Kinetics And Allosteric Mechanisms For The Hsp90 Chaperone Inhibitors Using Ai-Augmented Integrative Biophysical Studies, Chao Xu, Xianglei Zhang, Lianghao Zhao, Gennady M. Verkhivker, Fang Bai

Mathematics, Physics, and Computer Science Faculty Articles and Research

The binding kinetics of drugs to their targets are gradually being recognized as a crucial indicator of the efficacy of drugs in vivo, leading to the development of various computational methods for predicting the binding kinetics in recent years. However, compared with the prediction of binding affinity, the underlying structure and dynamic determinants of binding kinetics are more complicated. Efficient and accurate methods for predicting binding kinetics are still lacking. In this study, quantitative structure–kinetics relationship (QSKR) models were developed using 132 inhibitors targeting the ATP binding domain of heat shock protein 90α (HSP90α) to predict the dissociation rate …

An Injectable In Situ Forming Collagen/Alginate/Caso4 Composite Hydrogel For Tissue Engineering Applications: Optimization, Characterization And In Vitro Assessments, Samar A. Salim, Samar A. Salim

Nanotechnology Research Centre

In situ injectable hydrogels are effectively employed to fill irregular cavitary bone defects with initiating bone growth in targeted areas. Herein, an injectable composited hydrogel composed of collagen and alginate cross-linked in situ using different concentrations of calcium sulfate (0.15, 0.3 and 0.6%, wt./v) was synthesized. Recently, CaSO4 is frequently supported as a bone graft material for bone regeneration, owing to its biocompatibility and osteoconductive properties. Moreover, hydroxyapatite (Hap) after salinization-step by (3-Aminopropyl) triethoxysilane (APTES) was incorporated for further enhancing the osteoconductive property of injected hydrogels. All fabricated hydrogels were characterized by SEM, FTIR and XRD analyses. While physiochemical characteristics …

Eco-Friendly Hptlc Determination Of Paracetamol, Caffeine, Drotaverine Hcl And Two Of Their Official Impurities; Application To Assay And Content Uniformity Testing Of Tablet Dosage Form, Samia A. Tawfik, Nariman A. El-Ragehy, Maha A. Hegazy, Ghada A. Sedik

Bulletin of Faculty of Pharmacy Cairo University

The present work is focused on developing and validating an eco-friendly, sustainable and sensitive HPTLC method for the purpose of simultaneous determination of a five component mixture. This mixture includes paracetamol, caffeine, drotaverine HCl and the official impurities of the first two aforementioned drugs, namely; p-aminophenol and theophylline, in order. The developed method is based on application of planar chromatography using a developing system of ethyl acetate: methanol: acetic acid (8:1:2, by volume). Quantitative determination of the mentioned components was performed using UV detection. The parameters impacting chromatographic separation have been optimized. The cited compounds were effectively separated with retardation …

“The Role Of Artificial Intelligence In The Pharmaceutical Field: Enhancing Therapeutic Outcomes And Repurposing Through The Acceleration Of Drug Discovery”, Tonivie Valeriano

[Archive] Belmont University Research Symposium (BURS)

The development of new drugs and their repurposing have considerably benefited the field of pharmacy. It will not only affect the pharmaceutical sector but also its diverse facets of health will be significantly influenced. Yet, the development of innovative medical treatments necessitated a lengthy period of expectancy for human survival. Individual survival rates were decreasing over time before the development of the treatment. Humanity has a limited lifespan. Moreover, investments in new drugs often go unnoticed because of the prolonged and complex process of drug research and development (R&D). In the future of pharmacy, artificial intelligence will continue to have …

Methionyl-Trna Synthetase Synthetic And Proofreading Activities Are Determinants Of Antibiotic Persistence, Whitney N. Wood, Miguel Angel Rubio, Lorenzo Eugenio Leiva, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site …

Odevixibat: A Novel Bile Salt Inhibitor Treatment For Pruritus In Progressive Familial Intrahepatic Cholestasis, Farrah E. Flattmann, Farhan S. Mohiuddin, Anjuni Singh, Anamika Tandon, Stewart J. Lockett, Jon D. Hirsch, Chizoba N. Mosieri, Adam M. Kaye, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Chronic pruritus is defined as an itch lasting greater than six weeks. It can manifest from a wide variety of etiologies, as many different substances can act as pruritogens, such as steroids, histamine, progesterone, endogenous opioids, and serotonin. In the setting of cholestatic liver disease, increased bile acids play a major role in chronic pruritus. The itching in cholestatic liver disease is worsened in intensity at night and localized frequently to the palms, soles, knees, and other pressure sites. It can be hard to manage, affecting the quality of sleep and causing irritability, poor attention, and, in some cases, depression. …

Nebulization Based Inhalation Nanomedicine For Lung Cancer Treatments, Rahul Tiwari, Meghana Kolli, Neeraj Chauhan, Eswara Naga Hanuma, Vivek Kashyap, Subhash Chauhan, Murali Yallapu

Research Symposium

Background: Lung cancer is reported to have a high incidence rate and first leading cause of cancer-related morbidity and mortality across the world including in the United States. Noninvasive nebulized inhalation is a promising delivery strategy for lung, which can enhance the targeting efficiency and detention time interval of nanoparticles in the lung tissue, thus elevating the therapeutic index of therapeutic agent(s) at lower dosages. The aim of this study is to develop inhalable nanoparticles (INPs) for effective delivery of therapeutic agents in lung cancer cell lines and ex vivo models.

Methods: The inhalation nanoparticles (INPs) were prepared by solvent …

Mechanistic Investigation Of C—C Bond Activation Of Phosphaalkynes With Pt(0) Complexes, Roberto M. Escobar, Abdurrahman C. Ateşin, Christian Müller, William D. Jones, Tülay Ateşin

Research Symposium

Carbon–carbon (C–C) bond activation has gained increased attention as a direct method for the synthesis of pharmaceuticals. Due to the thermodynamic stability and kinetic inaccessibility of the C–C bonds, however, activation of C–C bonds by homogeneous transition-metal catalysts under mild homogeneous conditions is still a challenge. Most of the systems in which the activation occurs either have aromatization or relief of ring strain as the primary driving force. The activation of unstrained C–C bonds of phosphaalkynes does not have this advantage. This study employs Density Functional Theory (DFT) calculations to elucidate Pt(0)-mediated C–CP bond activation mechanisms in phosphaalkynes. Investigating the …

Real-Time Camp Dynamics In Live Cells Using The Fluorescent Camp Difference Detector In Situ, Isabella Cattani-Cavalieri, Jordyn Margolis, Camelia Anicolaesei, Francisco J. Nuñez, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

cAMP Difference Detector In Situ (cADDis) is a novel biosensor that allows for the continuous measurement of cAMP levels in living cells. The biosensor is created from a circularly permuted fluorescent protein linked to the hinge region of Epac2. This creates a single fluorophore biosensor that displays either increased or decreased fluorescence upon binding of cAMP. The biosensor exists in red and green upward versions, as well as green downward versions, and several red and green versions targeted to subcellular locations. To illustrate the effectiveness of the biosensor, the green downward version, which decreases in fluorescence upon cAMP binding, was …

Case Studies On Biomedical Innovation Systems In Major Countries, Xiaoling Ma

Bulletin of Chinese Academy of Sciences (Chinese Version)

The study focuses on the basic research, technological breakthroughs, transformation and commercialization of representative biomedical innovations over the past century—including penicillin, artemisinin, monoclonal antibodies, tumor immunotherapy, adenoviral gene therapy, mRNA vaccines, CRISPR/Cas9 gene editing, etc.—adopting a “dissecting the sparrow” case study methodology to conduct in-depth analyses (“double-clicking”) of each breakthrough, thereby mapping the institutional architectures and performance outcomes of national biomedical innovation systems and achieving a “seeing both trees and forest” perspective. Through comparative analysis, it reveals that the United States, compared with the United Kingdom, Japan, Germany and China, has developed a smooth technology transfer system and a mature …

Remodeling Anaplastic Thyroid Cancer's Aggressive Profile And Metabolic Signature By Natural Alkaloid Berberine, Tara Elizabeth Jarboe

NYMC Student Theses and Dissertations

Anaplastic thyroid cancer is a rare, fatal cancer with a five-year survival of 4%. Universally diagnosed at stage IV, anaplastic thyroid cancer is characterized by its lack of differentiation, rapid proliferative rate, highly inflammatory tumor microenvironment, and metabolic dysregulation. Refractory to all established therapies, anaplastic thyroid cancer requires a novel therapeutic approach that targets all of these drivers of anaplastic thyroid cancer carcinogenesis. We propose natural alkaloid berberine as a therapeutic with multitarget efficacy to alter mitochondrial metabolism and reprogram anaplastic thyroid cancer’s aggressive phenotype. Our in vitro model uses monocyte cell line U937, anaplastic thyroid cancer cell lines T238 …

Differential Effects Of Fucus Vesiculosus Fucoidan On Fibroblast And Macrophage Cell Lines Inflammatory Activation, Aleksandra Augustyniak, Joanna Przyborska, Helena Mcmahon

Publications

It is estimated that more than one-third of people aged over 16 reported living with inflammation-related chronic illness. Fucoidan, sulfated polysaccharide, has been proven to modulate immune response and inhibit inflammation in both in vitro and in vivo research. In the present study the effect of commercially available fucoidan from Fucus vesiculosus (with purity 97%) on immune response was investigated. Two cell lines, human fibroblasts (HDFa) and mouse macrophages (J774A.1) were used in the study. Cells were activated with pro-inflammatory stimulus (LPS/IFN-γ or PMA) and treated with fucoidan. Results of NO inhibition assay revealed that fucoidan has anti-inflammatory activity and …

The Effect Of Ethanol Treatment On The Protein Content Of Difi Exosomes, Kenzie Rushing

[Archive] Belmont University Research Symposium (BURS)

Colorectal cancer (CRC) is the second most common cause of cancer death in the United States in both men and women combined, second only to lung cancer.1 CRC metastasis is the primary cause of mortality largely due to therapy resistant cancer cells.2 Therefore, detection before metastasis is of great importance and could potentially lead to earlier detection and decreased mortality. Extracellular vesicles (EVs), including exosomes, are lipid bound vesicles secreted by cells3 that are involved in cell-cell communication and have been found to promote CRC progression and metastasis.4 The proteome of exosomes is thought to reflect that of the originating …

Single Dual-Specific Anti-Pd-L1/Tgf-Β Antibody Synergizes With Chemotherapy As Neoadjuvant Treatment For Pancreatic Ductal Adenocarcinoma: A Preclinical Experimental Study, Haoxiang Zhang, Jiaoshun Chen, Jianwei Bai, Jing Zhang, Shaoyi Huang, Liang Zeng, Pengfei Zhou, Qiang Shen, Tao Yin

School of Medicine Faculty Publications

AIMS: Chemotherapy resistance is an important cause of neoadjuvant therapy failure in pancreatic ductal adenocarcinoma (PDAC). BiTP is a single antibody that can simultaneously and dually target transforming growth factor-beta (TGF-β) and programmed cell death 1 ligand 1 (PD-L1). We attempted in this study to investigate the efficacy of BiTP in combination with first-line chemotherapy in PDAC. METHODS: Preclinical assessments of BiTP plus gemcitabine and nab-paclitaxel were completed through a resectable KPC mouse model (C57BL/6J). Spectral flow cytometry, tissue section staining, enzyme-linked immunosorbent assays, Counting Kit-8, transwell, and Western blot assays were used to investigate the synergistic effects. RESULTS: BiTP …

Contraception Methods And Varying Ovarian Cancer Risk, Caroline Veltri

D.U.Quark

Ovarian cancer (OC) is one of the most common, yet deadly, cancers women face. There are multiple ways it can be treated, such as hysterectomy, cytoreductive surgery, and/or chemotherapy, depending on the grade of the cancer. Important risk factors to note are genetics, talc usage, endometriosis, obesity, gene mutations, and cigarette smoking. Non-oral, long-acting contraception (LARC), such as IUDs (intrauterine device) and implants, are the most effective methods of pregnancy prevention. It is uncertain that they can protect against OC like oral contraceptives can. If LARCs can be proven useful in preventing OC, the mortality rate of OC will decrease, …

Β-Sheets Mediate The Conformational Change And Allosteric Signal Transmission Between The Aslov2 Termini, Sian Xiao, Mayar Terek Ibrahim, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

Avena sativa phototropin 1 light-oxygen-voltage 2 domain (AsLOV2) is a model protein of Per-Arnt-Sim (PAS) superfamily, characterized by conformational changes in response to external environmental stimuli. This conformational change begins with the unfolding of the N-terminal A'α helix in the dark state followed by the unfolding of the C-terminal Jα helix. The light state is characterized by the unfolded termini and the subsequent modifications in hydrogen bond patterns. In this photoreceptor, β-sheets are identified as crucial components for mediating allosteric signal transmission between the two termini. Through combined experimental and computational investigations, the Hβ …

Alkindi Sprinkle For Pediatric Patients With Primary Adrenocortical Insufficiency: A Narrative Review, Alan D. Kaye, Munira E. Khaled, Kristin Nicole Bembenick, John Lacey, Anamika Tandon, Rucha A. Kelkar, Alyssa G. Derouen, Corrado Ballaera, Debbie Chandler, Shahab Ahmadzadeh, Sahar Shekoohi, Giustino Varrassi

School of Medicine Faculty Publications

Adrenocortical insufficiency, also known as adrenal insufficiency (AI), is an endocrine disorder characterized by inadequate production of adrenal hormones, including glucocorticoids and mineralocorticoids (MCs). The condition can be categorized as primary, secondary, or tertiary AI, depending on the location of the defect. Classical symptoms of AI include weakness, fatigue, abdominal pain, tachycardia, hypotension, electrolyte imbalances, and hyperpigmentation. In children, the most common cause of AI is classical congenital adrenal hyperplasia, which results from a deficiency in the 21-hydroxylase enzyme. The 21-hydroxylase enzyme produces all steroids, such as cortisol and aldosterone. AI management primarily involves hormone replacement therapy, typically with oral …