A high-throughput assay platform to discover small molecule activators of the phospholipase PLC-γ2 to treat Alzheimer's disease.

A naturally occurring missense variant of the phospholipase C isozyme, PLC-γ2, harboring a single substitution (P522R) protects against several neurodegenerative diseases, including Alzheimer's disease. The phospholipase activity of PLC-γ2 (P522R) is slightly elevated relative to its wild-type counterpart, and the general consensus is that this increased activity in microglia confers protection against neurodegeneration. In order to phenocopy this protection, we have developed a high-throughput assay to identify small molecule activators of PLC-γ2.

Pharmacokinetics and Safety of Sulfamethoxazole-Trimethoprim After Oral Administration of Single and Multiple Doses to Rhode Island Red Chickens ().

Sulfamethoxazole-trimethoprim (SMZ-TMP), a commonly prescribed antibiotic for backyard hens, is neither Food and Drug Administration approved nor prohibited in laying hens in the United States. The aim of this study was to determine whether plasma concentrations above targeted minimum inhibitory concentration breakpoint values for Enterobacteriaceae could be achieved with oral dosing. Five Rhode Island red hens () were administered a single dose of 96 mg/kg SMZ-TMP (80 mg/kg SMZ and 16 mg/kg TMP) IV followed by the same dose orally after a washout period.

Oral administration of an extended-release formulation of nitrofurantoin results in high concentrations in the urine of dogs.

Objective: Sporadic bacterial cystitis in both dogs and humans is often caused by Escherichia coli. In humans, nitrofurantoin is a first-line antimicrobial for the treatment of bacterial cystitis but in dogs a lack of available data may be part of the reason it is only recommended as a second-line treatment. The objective of this preliminary study was to determine the plasma pharmacokinetics and urine concentrations of nitrofurantoin monohydrate-macrocrystalline in dogs.

A retrospective study of adverse drug events in anticoagulant administration with relevance to COVID-19.

Initial studies in COVID-19 patients reported lower mortality rates associated with the use of the drug heparin, a widely used anticoagulant. The objective of this analysis was to determine whether there are adverse events associated with the administration of anticoagulants, and specifically how this might apply in patients known to have COVID-19. Data for this study were obtained from the Food and Drug Administration's Adverse Event Reporting System (FAERS) public database and from the NIH's clinical trials website.

The COVID-19 Vaccine Conundrum: An Assessment of Vaccine Hesitancy Amongst Patients at a Federally Qualified Health Center.

With three COVID-19 vaccines currently authorized for use in the US, vaccine hesitancy has the potential to sabotage COVID-19 vaccination efforts and be detrimental to overall health outcomes. In order to realize the extent of vaccine hesitancy, an adequate understanding of the role that self-identified barriers and epidemiologic factors may play is timely and important. The objectives of this study were to 1) determine if there is a relationship between vaccine hesitancy and epidemiologic factors, and 2) identify perceived patient-reported barriers associated with receiving a COVID-19 vaccine.

Veterinary prescription errors in a community pharmacy setting: A retrospective review.

Background: Community pharmacies are poised to see more veterinary prescriptions as a result of increased pet ownership especially during the coronavirus disease 19 pandemic. Concern has been raised about the lack of veterinary pharmacy training that community pharmacists receive, but no studies have evaluated the actual prevalence of errors in veterinary prescriptions including the prevalence of prescription writing errors.

Objectives: This study identifies the prevalence of errors in veterinary prescriptions at independent community pharmacies.

Data mining methodology for response to hypertension symptomology-application to COVID-19-related pharmacovigilance.

Background: Potential therapy and confounding factors including typical co-administered medications, patient's disease states, disease prevalence, patient demographics, medical histories, and reasons for prescribing a drug often are incomplete, conflicting, missing, or uncharacterized in spontaneous adverse drug event (ADE) reporting systems. These missing or incomplete features can affect and limit the application of quantitative methods in pharmacovigilance for meta-analyses of data during randomized clinical trials.

Methods: Data from patients with hypertension were retrieved and integrated from the FDA Adverse Event Reporting System; 134 antihypertensive drugs out of 1131 drugs were filtered and then evaluated using the empirical Bayes geometric mean (EBGM) of the posterior distribution to build ADE-drug profiles with an emphasis on the pulmonary ADEs.

Availability of Didactic and Experiential Learning Opportunities in Veterinary Practice at US Pharmacy Programs.

To explore the availability of veterinary pharmacy didactic and experiential learning opportunities in US pharmacy programs. A 23-item questionnaire was sent to subscribers of the American Association of Colleges of Pharmacy Curriculum and Pharmacy Practice listservs, which reach 2,098 participants and 141 pharmacy programs. The Fisher exact test was used to evaluate the association of offering a didactic course and accepting credit from an outside program for veterinary pharmacy course and between pharmacy programs offering a veterinary didactic course and being affiliated with a Doctor of Veterinary Medicine program.

Pulmonary adverse drug event data in hypertension with implications on COVID-19 morbidity.

Hypertension is a recognized comorbidity for COVID-19. The association of antihypertensive medications with outcomes in patients with hypertension is not fully described. However, angiotensin-converting enzyme 2 (ACE2), responsible for host entry of the novel coronavirus (SARS-CoV-2) leading to COVID-19, is postulated to be upregulated in patients taking angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs).

Egg residue and depletion in Rhode Island Red hens (Gallus gallus domesticus) following multiple oral doses of trimethoprim-sulfamethoxazole.

Sulfamethoxazole-Trimethoprim residues in eggs can cause risks to human health. The most common cause of residues in eggs results from failure to meet an appropriate withdrawal interval. The aim of this study was to determine the quantity and duration of sulfamethoxazole-trimethoprim residues in eggs and evaluate the drug elimination parameters in egg components and whole egg to better estimate the withdrawal interval of sulfamethoxazole and trimethoprim following oral administration for 7 days at a purposed dosage regimen (time average 46 mg kg day for sulfamethoxazole, time average 25 mg kg day for trimethoprim).

Insulin potentiates essential amino acids effects on mechanistic target of rapamycin complex 1 signaling in MAC-T cells.

Different models of lactation offer conflicting evidence as to whether insulin signaling is required for AA to stimulate mechanistic target of rapamycin complex 1 (mTORC1) activity. We hypothesized that insulin potentiates essential AA stimulation of mTORC1 activity in the MAC-T mammary epithelial cell line. Here, our objective was to assess mTORC1 signaling activity in response to insulin and individual or grouped essential AA.

Ovariectomy uncouples lifespan from metabolic health and reveals a sex-hormone-dependent role of hepatic mTORC2 in aging.

Inhibition of mTOR (mechanistic Target Of Rapamycin) signaling by rapamycin promotes healthspan and longevity more strongly in females than males, perhaps because inhibition of hepatic mTORC2 (mTOR Complex 2) specifically reduces the lifespan of males. Here, we demonstrate using gonadectomy that the sex-specific impact of reduced hepatic mTORC2 is not reversed by depletion of sex hormones. Intriguingly, we find that ovariectomy uncouples lifespan from metabolic health, with ovariectomized females having improved survival despite paradoxically having increased adiposity and decreased control of blood glucose levels.

Pharmacologic inhibition of mTORC1 mimics dietary protein restriction in a mouse model of lactation.

Background: Understanding the mechanisms of N utilization for lactation can lead to improved requirement estimates and increased efficiency, which modern dairy diets currently fail to maximize. The mechanistic target of rapamycin complex 1 (mTORC1) is a central hub of translation regulation, processing extra- and intra-cellular signals of nutrient availability and physiological state, such as amino acids and energy. We hypothesized that dietary amino acids regulate lactation through mTORC1, such that inhibition of mTORC1 will lead to decreased lactation performance when amino acids are not limiting.

Hypothalamic mTORC2 is essential for metabolic health and longevity.

The mechanistic target of rapamycin (mTOR) is an evolutionarily conserved protein kinase that regulates growth and metabolism. mTOR is found in two protein complexes, mTORC1 and mTORC2, that have distinct components and substrates and are both inhibited by rapamycin, a macrolide drug that robustly extends lifespan in multiple species including worms and mice. Although the beneficial effect of rapamycin on longevity is generally attributed to reduced mTORC1 signaling, disruption of mTORC2 signaling can also influence the longevity of worms, either positively or negatively depending on the temperature and food source.