Plasma fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxachola-4,6-dien-24-oic acid indicate severity of liver cirrhosis.

Two 3-oxo-Δ fetal bile acids, 3-oxachola-4,6-dien-24-oic acid (1) and 7α-hydroxy-3-oxochol-4-en-24-oic acid (2), occur normally in the human fetus but remain elevated in neonates and children with severe cholestatic liver disease due to an autosomal recessive inborn error of metabolism affecting Δ-3-oxo-steroid 5β-reductase (AKR1D1). Relatively little is known about 1 and 2 in adult patients with liver disease. The chemical synthesis of 1 and 2 is therefore described and their quantitation in plasma by ultrarapid chromatography-triple quadrupole mass spectrometry.

A retrospective evaluation of vitamin K for hemoptysis in adult cystic fibrosis patients.

Objectives: Hemoptysis is a complication in cystic fibrosis (CF) patients, and is associated with pulmonary exacerbations and hospitalizations. Pancreatic insufficiency is common in CF patients, and therefore these patients may benefit from the use of vitamin K therapy.

Methods: This was an observational study conducted in adult CF patients aiming to describe the utilization of vitamin K therapy in the setting of hemoptysis during an acute CF pulmonary exacerbation.

Physiologically based pharmacokinetic modeling of altered tizanidine systemic exposure by CYP1A2 modulation: Impact of drug-drug interactions and cigarette consumption.

Tizanidine is an alpha2-adrenergic agonist, used to treat spasticity associated with multiple sclerosis and spinal injury. Tizanidine is primarily metabolized by CYP1A2 and is considered a sensitive index substrate for this enzyme. The physiologically based pharmacokinetic (PBPK) modeling platform Simcyp® was used to evaluate the impact of CYP1A2 modulation on tizanidine exposure through drug-drug interactions (DDIs) and host-dependent habits (cigarette smoking).

Pediatric Nephrotic Syndrome: Pharmacologic and Nutrition Management.

Nephrotic syndrome is a common kidney disease during childhood that is characterized by alterations in glomerular filtration and leads to protein, fluid, and nutrient loss in the urine. Most patients experience peripheral, gravity-dependent edema; however, serious cases exhibit anasarca and ascites. Many long-term complications of the disease exist due to the underlying pathology and the therapies used for treatment, including metabolic bone disease, micronutrient deficiencies, and hyperlipidemia.

Angiotensin receptor neprilysin inhibitor use in patients with left ventricular assist devices: A single-center experience.

Though left ventricular assist devices (LVADs) are an increasingly common therapy for ACC/AHA Stage D heart failure, the optimal medical therapy for patients with LVADs is not known. We sought to evaluate the safety and efficacy of angiotensin receptor neprilysin inhibitor (ARNi) therapy in our single center LVAD patient experience. We evaluated patients implanted with LVADs at Columbia University Irving Medical Center between August 2010 and May 2019, and who were treated with an ARNi for at least 3 months.

Loop Diuretics: Clinical Application Information for Nephrology Nurses and Practitioners.

Loop diuretic medications work by inhibiting sodium reabsorption in the renal tubules. The net effect is increasing in urinary sodium and water excretion. Loop diuretics are routinely used for many clinical indications, and nephrology practitioners are well informed in the management of their use in daily practice.

Protocol development, validation, and troubleshooting of in-situ fiber optic bathless dissolution system (FODS) for a pharmaceutical drug testing.

Currently, there is no systematic approach available for the validation, quantitative assessment, and troubleshooting for the in-situ fiber optic/bathless dissolution system (FODS). In this report, a dissolution protocol was developed and validated for a model product, chlorpheniramine maleate (CPM) 4 mg IR tablets. Dissolution runs were conducted at 37 ± 0.

A current review of the safety of cystic fibrosis transmembrane conductance regulator modulators.

What Is Known And Objective: Treatment with cystic fibrosis transmembrane conductance regulator (CFTR) modulators has led to improved clinical outcomes and an increase in lifespans of cystic fibrosis (CF) patients. As CF patients continue to live longer, they are at risk for developing adverse drug reactions associated with polypharmacy and CFTR modulators.

Comment: The authors aim to describe safety concerns of the current combination CFTR modulators, based upon a literature review, including notable safety concerns and recommendations for drug-drug interactions.

Solid self-microemulsifying nutraceutical delivery system for hesperidin using quality by design: assessment of biopharmaceutical attributes and shelf-life.

Aim: The present study endeavours to develop a solid self-microemulsifying nutraceutical drug delivery system for hesperidin (HES) using quality by design (QbD) to improve its biopharmaceutical attributes.

Methods: A 3 full factorial design was employed to study the influence of factors on selected responses. Risk assessment was performed by portraying Ishikawa fishbone diagram and failure mode effect analysis (FMEA).

Discovery and SAR of Novel Disubstituted Quinazolines as Dual PI3Kalpha/mTOR Inhibitors Targeting Breast Cancer.

The dual PI3Kα/ m TOR inhibitors represent a promising molecularly targeted therapy for cancer. Here, we documented the discovery of new 2,4-disubstituted quinazoline analogs as potent dual PI3Kα/sm TOR inhibitors. Our structure based chemistry endeavor yielded six excellent compounds , and with single/double digit nanomolar IC values against both enzymes and acceptable aqueous solubility and stability to oxidative metabolism.

(2,3)-Dihydroxybutanoic Acid Synthesis as a Novel Metabolic Function of Mutant Isocitrate Dehydrogenase 1 and 2 in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) frequently harbors mutations in isocitrate 1 () and 2 () genes, leading to the formation of the oncometabolite (2)-hydroxyglutaric acid (2R-HG) with epigenetic consequences for AML proliferation and differentiation. To investigate if broad metabolic aberrations may result from and mutations in AML, plasma metabolomics was conducted by gas chromatography-mass spectrometry (GC-MS) on 51 AML patients, 29 / wild-type (WT), 9 with IDH1R132, 12 with IDH2R140 and one with IDH2R172 mutations. Distinct metabolic differences were observed between IDH1/2 WT, and patients that comprised 22 plasma metabolites that were mainly amino acids.

Anemia in Children With Inflammatory Bowel Disease: A Position Paper by the IBD Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition.

Anemia is one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD). It can be asymptomatic or associated with nonspecific symptoms, such as irritability, headaches, fatigue, dizziness, and anorexia. In IBD patients, the etiology of anemia is often multifactorial.

Clinical and economic impact of the use of dexmedetomidine for sedation in the intensive care unit compared to propofol.

Background Despite the advantages of dexmedetomidine (DEX) over propofol (PRO) including minimal respiratory depression and the potential for preventing and/or treating intensive care unit (ICU) delirium, PRO has been the preferred agent due to its lower cost. However, the acquisition cost of DEX has considerably decreased as a generic version of DEX has recently become available. Objective To evaluate clinical and economic outcomes of DEX-based sedation compared to PRO in the ICU.

Current Perspectives of Anticoagulation in Patients With COVID-19.

Thromboembolism and myocardial injury is common in patients with COVID-19. Low-molecular-weight heparin appears to be associated with a good prognosis in patients with COVID-19 and has the ability to reduce coagulation and inflammation markers. Hospitalized patients with COVID-19 should be placed on thromboprophylaxis with the option of full therapeutic anticoagulation or tissue plasminogen activator in high-risk or mechanically ventilated patients.

A heart failure themed escape room approach to enhance pharmacy student learning.

Introduction: The purpose of this study was to design, pilot, and evaluate the efficacy of an educational escape room to enhance second professional year doctor of pharmacy students' knowledge of heart failure medicinal chemistry, pharmacology, and therapeutics in an integrated Modular Organ Systems Therapeutics (MOST) course and to assess students' perceptions of the game.

Methods: Heart failure pharmacology, medicinal chemistry, and pharmacotherapeutics were taught in MOST prior to the escape room activity. Students were randomized into groups of approximately eight.

Development and Validation of Sample Preparation and an HPLC Analytical Method for Dissolution Testing in Fed-State Simulated Gastric Fluid-Illustrating Its Application for Ibuprofen and Ketoconazole Immediate Release Tablets.

Dissolution testing and solubility determinations in different biorelevant media have gained considerable interest in the pharmaceutical industry from early-stage development of new products to forecasting bioequivalence. Among all biorelevant fluids, the preparation of fed-state simulated gastric fluid (FeSSGF) and handling of samples from dissolution/solubility testing in FeSSGF is considered to be relatively challenging. Challenges include maintaining the stability of FeSSGF medium upon sampling, filtration, and mitigating analytical interference of excipients and milk components.

In and Beyond COVID-19: US Academic Pharmaceutical Science and Engineering Community Must Engage to Meet Critical National Needs.

The supply of affordable, high-quality pharmaceuticals to US patients has been on a critical path for decades. In and beyond the COVID-19 pandemic, this critical path has become tortuous. To regain reliability, reshoring of the pharmaceutical supply chain to the USA is now a vital national security need.

A Call to Action: The Role of Antiretroviral Stewardship in Inpatient Practice, a Joint Policy Paper of the Infectious Diseases Society of America, HIV Medicine Association, and American Academy of HIV Medicine.

Persons living with human immunodeficiency virus (HIV) and others receiving antiretrovirals are at risk for medication errors during hospitalization and at transitions of care. These errors may result in adverse effects or viral resistance, limiting future treatment options. A range of interventions is described in the literature to decrease the occurrence or duration of medication errors, including review of electronic health records, clinical checklists at care transitions, and daily review of medication lists.

Pharmacokinetics of linezolid for methicillin-resistant Staphylococcus aureus pneumonia in an adult receiving extracorporeal membrane oxygenation.

Purpose: We present a case of a 55-year-old man post right lung transplantation receiving ECMO for treatment of respiratory failure secondary to methicillin-resistant Staphylococcus aureus (MRSA) pneumonia.

Summary: Extracorporeal membrane oxygenation (ECMO) is a frequently utilized support therapy for patients with cardiac and/or respiratory failure. Dosing of medications during ECMO can be challenging due to several factors, including sequestration of medications within ECMO circuits, alterations in volume of distribution, and changes in drug clearance.

Contribution of Crystal Lattice Energy on the Dissolution Behavior of Eutectic Solid Dispersions.

In the literature, it is reported that eutectics lead to the enhanced dissolution of a poorly soluble compound. However, the solubility theory suggests that since crystal structures of two components are unchanged that all else being equal, the dissolution rates of a fused mixture (FM) should be the same as a physical mixture (PM). The influence of crystal lattice energy on dissolution profiles was investigated using the PM and FM.

Stress-Based Production, and Characterization of Glutathione Peroxidase and Glutathione S-Transferase Enzymes From .

More attention has been recently directed toward glutathione peroxidase and s-transferase enzymes because of the great importance they hold with respect to their applications in the pharmaceutical field. This work was conducted to optimize the production and characterize glutathione peroxidase and glutathione s-transferase produced by KU720558 using Plackett-Burman and Box-Behnken statistical designs. To assess the impact of the culture conditions on the microbial production of the enzymes, colorimetric methods were used.

Management of type 2 diabetes: consensus of diabetes organizations.

Despite the advances in diabetes management, people with diabetes are not reaching their target glycemic goals. Healthcare professionals often fail to initiate, escalate, or de-intensify therapy when indicated. There are several organizations that provide guidance on the management of diabetes to assist the practitioner in achieving improved glycemic control, and this can cause confusion to the practitioner on which organizations' guidance to follow.

Effects of compaction pressure, speed and punch head profile on the ultrasonically-extracted physical properties of pharmaceutical compacts.

Despite a well-established manufacturing-process understanding, tablet quality issues are frequently encountered during various stages of drug-product development. Compact breaking force (tensile strength), capping and friability are among the commonly observed characteristics that determine the integrity, quality and manufacturability of tablets. In current study, a design space of the compaction pressure, compaction speed and head flat types is introduced for solid dosage compacts prepared from pure silicified microcrystalline cellulose, a popular tableting excipient.

Role of Structure, Microenvironmental pH, and Speciation To Understand the Formation and Properties of Febuxostat Eutectics.

Cocrystallization studies were undertaken to improve the solubility of a highly water-insoluble drug, febuxostat (FXT), used in the treatment of gout and hyperuricemia. A liquid-assisted grinding (LAG) method was successfully employed, starting with the screening of various coformers for obtaining cocrystals. However, in this process, three eutectic systems with coformers (probenecid, adipic acid, and α-ketoglutaric acid) were formed.