Role of Markers of Heavy Metal Metabolism in Identification of Hepatic Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease (NAFLD)
Oxidative stress; hepatic fibrosis; non-alcoholic fatty liver disease; Heavy Metals; non-alcoholic steatohepatitis (NASH)
INTRODUCTION: Fibrosis & nonalcoholic steatohepatitis (NASH) are important predictors of long term prognosis in patients with non-alcoholic fatty liver disease (NAFLD). Oxidative stress (OS) has been shown to play a central role in progression of NAFLD, & changes in proteins associated with metal homeostasis may exacerbate OS. We investigated relationship of proteins related to transition metal metabolism with fibrosis in NAFLD. METHODS: Adult patients (>18y) who underwent liver biopsy for clinically suspected NAFLD at our institution were included. We retrospectively collected serum levels of ceruloplasmin (Cp), ferritin, iron, & transferrin saturation (Tsat) within 3 months of liver biopsy & calculated Cp/Tsat ratio (CT ratio) & Cp/Ferritin ratio (CF ratio). Histologic features were scored by an experienced pathologist using Non-alcoholic Steatohepatitis Clinical Research Network criteria. Fibrosis was staged as (0 - 4). Independent T test were used to compare the means & receiver operating characteristics (ROC) curves were plotted for assessing area under curve (AUC), sensitivity (Sn) & specificity (Sp). RESULTS: 174 patients were included in final analysis. The mean age of subjects was 48 y. Baseline features are depicted in Table 1. Biopsy proven NASH was seen in 61.5% of liver biopsies. No fibrosis was seen in 29.3% of liver biopsies & Stage 1, 2,3& 4 fibrosis were seen in 29.9%, 10.9%, 14.3% & 15.55% of samples. Mean Tsat was significantly higher (24.41% v/s 38.27%, P < 0.0001) & Cp (mg/dl) (27.82 v/s 24.91, P = 0.03) significantly lower between patients with advanced fibrosis (AF) (3-4) v/s early fibrosis (EF) (0-2). The mean CT ratio was also higher in patients with EF v/s AF (1.54 v/s 1.02, P = 0.01). The mean Tsat of patients with fibrosis v/s without fibrosis was higher (31.4% v/s 21.57% P < 0.005) however mean Cp (mg/dl) values were not significantly different (27.88 v/s 27.58, P = 0.42). The ROC curves show CF ratio (Figure 1) at a cut off of 0.10 had AUC = 0.61 (Sn = 70%, Sp = 52% P = 0.01) to detect any fibrosis & CT ratio (Figure 2) at a cut off 0.86 had AUC = 0.65 (Sn = 69%, Sp = 50% P = 0.002) for differentiating EF v/s AF. CONCLUSION: Our data reveals changes in ceruloplasmin: transferrin system, which decreases the content of toxic ions of Fe2+ in NAFLD. Tsat, Cp, CF ratio & CT ratio are useful non-invasive biomarkers in identifying NAFLD patients with fibrosis. Markers of heavy metal metabolism can spare patients from liver biopsies & can be potential therapeutic targets in future.
Aggarwal Manik;Mitchell B;Singh AD;Kasumov T;McCullough A
American Journal Of Gastroenterology
2020
2020-10
journalArticle
<a href="http://doi.org/10.14309/01.ajg.0000706532.82398.af" target="_blank" rel="noreferrer noopener">10.14309/01.ajg.0000706532.82398.af</a>
MITOCHONDRIAL DYSFUNCTION IN OSTEOARTHRITIS AND AGED CARTILAGE TRIGGERS INFLAMMATORY RESPONSE AND MATRIX DEGRADATION VIA ROS MEDIATED ACTIVATION OF JNK-MAPK/CFOS-AP1 AXIS IN CHONDROCYTES
Ansari M Y; Ahmad N; Voleti S; Wase S; Malik M; Novak K; Haqqi Tariq M
Osteoarthritis and Cartilage
2020
2020-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
n/a
The Effect of Pharmacy-Led, Small-Group Academic Detailing on Prescribing Patterns in an Ambulatory Care Clinic
medical education; clinical; medications; pharmacy; interventions; Pharmacology & Pharmacy; impact; academic detailing; ambulatory care; community practice; prescribing patterns; prior authorization
Background: While academic detailing seems to be the most promising intervention to improve prescribing patterns, implementation could be challenging for small community practices. Objective: A pharmacy-led, interactive, and tailored small-group academic detailing in a federally qualified health center is described. The primary objective of the study was to determine if the small-group academic detailing improved the prescribing patterns of the medical providers for select disease states: type 2 diabetes mellitus (T2DM), hyperlipidemia (HLD), and essential hypertension (HTN). Methods: Prescribing patterns in a federally qualified health center were examined in relation to small-group academic detailing sessions from April 2010 to March 2015. The markers for improvement were the increase in utilizing metformin and statins in patients diagnosed with T2DM and HLD, respectively, and the reduction of beta-blocker use in patients diagnosed with essential HTN. Changes in prescribing patterns were evaluated using Pearson's chi(2) and Fisher's exact tests. Results: The average number of active, adult patients with T2DM, HLD, and essential HTN was 839, 1768, and 2547, respectively. Utilization of metformin in T2DM increased from 5.5% at baseline to 37.7%, statin utilization in HLD increased from 77.1% to 86.9%, and beta-blocker use in HTN decreased from 17.9% to 13.8% (P < .005). Conclusions: A pharmacy-led, small-group academic detailing program improved and maintained appropriate prescribing patterns in an underserved community practice. This study serves as a successful pilot emphasizing the pharmacist's role as an educator and a resource to medical providers regarding appropriate medication use.
Awad M H; Ulbrich T R; Furdich K M; Schneider S R; Gothard M D
Journal of Pharmacy Technology
2019
2019-04
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1177/8755122518818826" target="_blank" rel="noreferrer noopener">10.1177/8755122518818826</a>
The Effect of Pharmacy-Led, Small-Group Academic Detailing on Prescribing Patterns in an Ambulatory Care Clinic.
Adrenergic Beta-Antagonists -- Therapeutic Use; Adult; Ambulatory Care Facilities; Chi Square Test; Descriptive Statistics; Diabetes Mellitus; Education; Essential Hypertension -- Drug Therapy; Fisher's Exact Test; Human; Hyperlipidemia -- Drug Therapy; Medically Underserved Area; Metformin -- Therapeutic Use; Non-Traditional; Outcomes of Education; Pharmacy Service; Physicians -- Education; Prescribing Patterns -- Education; Statins -- Therapeutic Use; Type 2 -- Drug Therapy
Background: While academic detailing seems to be the most promising intervention to improve prescribing patterns, implementation could be challenging for small community practices. Objective: A pharmacy-led, interactive, and tailored small-group academic detailing in a federally qualified health center is described. The primary objective of the study was to determine if the small-group academic detailing improved the prescribing patterns of the medical providers for select disease states: type 2 diabetes mellitus (T2DM), hyperlipidemia (HLD), and essential hypertension (HTN). Methods: Prescribing patterns in a federally qualified health center were examined in relation to small-group academic detailing sessions from April 2010 to March 2015. The markers for improvement were the increase in utilizing metformin and statins in patients diagnosed with T2DM and HLD, respectively, and the reduction of β-blocker use in patients diagnosed with essential HTN. Changes in prescribing patterns were evaluated using Pearson's χ2 and Fisher's exact tests. Results: The average number of active, adult patients with T2DM, HLD, and essential HTN was 839, 1768, and 2547, respectively. Utilization of metformin in T2DM increased from 5.5% at baseline to 37.7%, statin utilization in HLD increased from 77.1% to 86.9%, and β-blocker use in HTN decreased from 17.9% to 13.8% (P < .005). Conclusions: A pharmacy-led, small-group academic detailing program improved and maintained appropriate prescribing patterns in an underserved community practice. This study serves as a successful pilot emphasizing the pharmacist's role as an educator and a resource to medical providers regarding appropriate medication use.
Awad Magdi H; Ulbrich Timothy R; Furdich Kenneth M; Schneider Stacy R; Gothard M David
Journal of Pharmacy Technology
2019
2019-04
<a href="http://doi.org/10.1177/8755122518818826" target="_blank" rel="noreferrer noopener">10.1177/8755122518818826</a>
A retrotransposon gag-like-3 gene RTL3 and SOX-9 co-regulate the expression of COL2A1 in chondrocytes.
gene regulation; chondrogenesis; extracellular matrix; chondrocyte; ZCCHC5/RTL3; RTL3; ZCCHC5
PURPOSE: Transposable elements are known to remodel gene structure and provide a known source of genetic variation. Retrotransposon gag-like-3 (RTL3) is a mammalian retrotransposon-derived transcript (MART) whose function in the skeletal tissue is unknown. This study aimed to elucidate the biological significance of RTL3 in chondrogenesis and type-II collagen (COL2A1) gene expression in chondrocytes. MATERIALS AND METHODS: Expression of RTL3, SOX-9 and COL2A1 mRNAs was determined by TaqMan assays and the protein expression by immunoblotting. RTL3 and Sox-9 depletion in human chondrocytes was achieved using validated siRNAs. An RTL3 mutant (∆RTL3) lacking the zinc finger domain was created using in vitro mutagenesis. Forced expression of RTL3, ∆RTL3, and SOX-9 was achieved using CMV promoter containing expression plasmids. CRISPR-Cas9 was utilized to delete Rtl3 and create a stable ATDC5(Rlt3-/-) cell line. Matrix deposition and Col2a1 quantification during chondrogenesis were determined by Alcian blue staining and Sircol™ Soluble Collagen Assay, respectively. RESULTS: RTL3 is not ubiquitously expressed but showed strong expression in cartilage, chondrocytes and synoviocytes but not in muscle, brain, or other tissues analyzed. Loss-of-function and gain-of-function studies demonstrated a critical role of RTL3 in the regulation of SOX-9 and COL2A1 expression and matrix synthesis during chondrogenesis. Both RTL3 and SOX-9 displayed co-regulated expression in chondrocytes. Gene regulatory activity of RTL3 requires the c-terminal CCHC zinc-finger binding domain. CONCLUSIONS: Our results identify a novel regulatory mechanism of COL2A1 expression in chondrocytes that may help to further understand the skeletal development and the pathogenesis of diseases with altered COL2A1 expression.
Ball HC;Ansari M Y;Ahmad N;Novak K;Haqqi TM
Connective Tissue Research
2020
2020-10-12
journalArticle
<a href="http://doi.org/10.1080/03008207.2020.1828380" target="_blank" rel="noreferrer noopener">10.1080/03008207.2020.1828380</a>
Interprofessional Education for Team-Based Geriatric Care
Geriatrics & Gerontology
Presentation A161 at the American Geriatrics Society 2019 Annual Meeting
Brown D K; Drost J; Fosnight S; Morgan A; Hazelett S
Journal of the American Geriatrics Society
2019
2019-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/jgs.15898" target="_blank" rel="noreferrer noopener">10.1111/jgs.15898</a>
L-plastin, a novel regulator of microglial activation in parkinsons disease
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease worldwide behind Alzheimer’s disease. One prominent feature of PD is the marked loss of dopaminergic and motor dysfunction. Currently, there are no therapies to effectively slow disease progression. Neuroinflammation is a major contributing factor in neurodegeneration diseases including PD. Microglia, a type of glial cell, are primary regulators of neuroinflammation and these cells are capable of assuming activation states ranging from inflammatory to anti‐inflammatory and reparative. Thus methods to combat microglial inflammation or promote microglial anti‐inflammatory and reparative effects show promise as treatments to slow neurodegeneration. L‐plastin (LPL) is an acting bundling protein and other research has shown that LPL plays a role in osteoclast function, T‐cell activation, and it may be involved in the NLRP3 inflammasome activation in macrophages. It has been shown in osteoclasts, that LPL phosphorylation at serine 5 plays a role in sealing zone formation. Using a peptide inhibitor to block phosphorylation of serine 5 on LPL prevented sealing zone formation and inhibited osteoclast‐mediated bone resorption. Given the evidence that LPL may play a role in inflammasome activation in macrophages, we investigated if LPL may play a role in microglial activation. To assess the function of LPL in the microglial inflammatory response, we utilized qPCR, Western blot, and immunofluorescence techniques. We show here that lipopolysaccharide (LPS) treatment induces LPL phosphorylation at serine 5, as well as increased Lcp1 mRNA expression. Furthermore, using a TAT‐fused peptidomimetic inhibitor of LPL phosphorylation significantly reduced LPS‐induced inflammatory gene (Il‐1b, Il‐6, Tnfa) expression. For this study, an acute 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model was also used. Male (10‐week‐old) C57BL/6N mice were treated with four injections (one every two hours) of either saline or 15mg/kg of MPTP. Mice were then sacrificed two days after the last injection and striatum and hindbrain were isolated. Two days after MPTP treatment is when peak inflammation occurs in the brain. We found that Lcp1 mRNA expression was significantly increased in the striatum of MPTP‐treated mice compared to saline‐treated mice. These results suggest that LPL may play a role in the microglial inflammatory response, and that LPL inhibition may be a novel way to combat neuroinflammation and neurodegeneration. We are currently staining for phosphorylated LPL in the microglia of MPTP treated mice. Furthermore, we have obtained LPL KO mice to assess the in vivo function of LPL in mouse models of PD.
Budge K;Richardson JR;Safadi F
Faseb Journal
2020
2020-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1096/fasebj.2020.34.s1.09750" target="_blank" rel="noreferrer noopener">10.1096/fasebj.2020.34.s1.09750</a>
Transgenic Overexpression of GPNMB Protects Against MPTP-Induced Neurodegeneration.
GPNMB; Microglia; MPTP; Neuroinflammation; Neuroprotective; Parkinson's disease
Parkinson's disease (PD) is a progressive neurodegenerative disease highlighted by a marked loss of dopaminergic cell loss and motor disturbances. Currently, there are no drugs that slow the progression of the disease. A myriad of factors have been implicated in the pathogenesis and progression of PD including neuroinflammation. Although anti-inflammatory agents are being evaluated as potential disease-modifying therapies for PD, none has proven effective to date, suggesting that new and novel targets are needed. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that has recently been shown to reduce inflammation in astrocytes and to be increased in post-mortem PD brain samples. Here we show that transgenic overexpression of GPNMB protects against dopaminergic neurodegeneration in a
Budge Kevin; Neal Matthew L; Richardson Jason R; Safadi Fayez F
Molecular neurobiology
2020
2020-05-20
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1007/s12035-020-01921-6" target="_blank" rel="noreferrer noopener">10.1007/s12035-020-01921-6</a>
Acute exposure to a glyphosate-containing herbicide formulation inhibits Complex II and increases hydrogen peroxide in the model organism Caenorhabditis elegans.
C. elegans; Glyphosate; Hydrogen peroxide; Mitochondrial inhibition; Oxygen consumption; Reactive oxygen species
Glyphosate-based herbicides, such as Touchdown (TD) and Roundup, are among the most heavily-used herbicides in the world. While the active ingredient is generally considered non-toxic, the toxicity resulting from exposure to commercially-sold formulations is less clear. In many cases, cell cultures or various model organisms exposed to glyphosate formulations show toxicity and, in some cases, lethality. Using Caenorhabditis elegans, we assessed potential toxic mechanisms through which a highly-concentrated commercial formulation of TD promotes neurodegeneration. Following a 30-min treatment, we assayed mitochondrial electron transport chain function and reactive oxygen species (ROS) production. Initial oxygen consumption studies indicated general mitochondrial inhibition compared to controls ((*)p \textless 0.05). When Complex II activity was further assessed, inhibition was observed in all TD-treated groups ((*)p \textless 0.05). Complex IV activity, however, was not adversely affected by TD. This electron transport chain inhibition also resulted in reduced ATP levels ((*)p \textless 0.05). Furthermore, hydrogen peroxide levels, but not other ROS, were increased ((*)p \textless 0.05). Taken together, these data indicate that commercially-available formulations of TD may exert neurotoxicity through Complex II (succinate dehydrogenase) inhibition, decreased ATP levels, and increased hydrogen peroxide production.
Burchfield Shelbie L; Bailey Denise C; Todt Callie E; Denney Rachel D; Negga Rekek; Fitsanakis Vanessa A
Environmental toxicology and pharmacology
2019
2019-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.etap.2018.12.019" target="_blank" rel="noreferrer noopener">10.1016/j.etap.2018.12.019</a>
Acute exposure to a glyphosate-containing herbicide formulation inhibits Complex II and increases hydrogen peroxide in the model organism Caenorhabditis elegans.
C. elegans; Glyphosate; *hydrogen peroxide; Mitochondrial inhibition; Oxygen Consumption; *Reactive oxygen species; Animals; Reactive Oxygen Species/metabolism; Adenosine Triphosphate/metabolism; Herbicides/*toxicity; Caenorhabditis elegans/*drug effects/metabolism; Electron Transport Complex II/*antagonists & inhibitors/metabolism; Glycine/*analogs & derivatives/toxicity
Glyphosate-based herbicides, such as Touchdown (TD) and Roundup, are among the most heavily-used herbicides in the world. While the active ingredient is generally considered non-toxic, the toxicity resulting from exposure to commercially-sold formulations is less clear. In many cases, cell cultures or various model organisms exposed to glyphosate formulations show toxicity and, in some cases, lethality. Using Caenorhabditis elegans, we assessed potential toxic mechanisms through which a highly-concentrated commercial formulation of TD promotes neurodegeneration. Following a 30-min treatment, we assayed mitochondrial electron transport chain function and reactive oxygen species (ROS) production. Initial oxygen consumption studies indicated general mitochondrial inhibition compared to controls ((*)p < 0.05). When Complex II activity was further assessed, inhibition was observed in all TD-treated groups ((*)p < 0.05). Complex IV activity, however, was not adversely affected by TD. This electron transport chain inhibition also resulted in reduced ATP levels ((*)p < 0.05). Furthermore, hydrogen peroxide levels, but not other ROS, were increased ((*)p < 0.05). Taken together, these data indicate that commercially-available formulations of TD may exert neurotoxicity through Complex II (succinate dehydrogenase) inhibition, decreased ATP levels, and increased hydrogen peroxide production.
Burchfield Shelbie L; Bailey Denise C; Todt Callie E; Denney Rachel D; Negga Rekek; Fitsanakis Vanessa A
Environmental toxicology and pharmacology
2019
2019-02
<a href="http://doi.org/10.1016/j.etap.2018.12.019" target="_blank" rel="noreferrer noopener">10.1016/j.etap.2018.12.019</a>
Transient receptor potential vanilloid 4 channel deletion regulates pathological but not developmental retinal angiogenesis.
neovascularization; TRPV4; mechanotransduction; ECM stiffness; human retinal endothelial cells
Transient receptor potential vanilloid 4 (TRPV4) channels are mechanosensitive ion channels that regulate systemic endothelial cell (EC) functions such as vasodilation, permeability, and angiogenesis. TRPV4 is expressed in retinal ganglion cells, Müller glia, pigment epithelium, microvascular ECs, and modulates cell volume regulation, calcium homeostasis, and survival. TRPV4-mediated physiological or pathological retinal angiogenesis remains poorly understood. Here, we demonstrate that TRPV4 is expressed, functional, and mechanosensitive in retinal ECs. The genetic deletion of TRPV4 did not affect postnatal developmental angiogenesis but increased pathological neovascularization in response to oxygen-induced retinopathy (OIR). Retinal vessels from TRPV4 knockout mice subjected to OIR exhibited neovascular tufts that projected into the vitreous humor and displayed reduced pericyte coverage compared with wild-type mice. These results suggest that TRPV4 is a regulator of retinal angiogenesis, its deletion augments pathological retinal angiogenesis, and that TRPV4 could be a novel target for the development of therapies against neovascular ocular diseases.
Cappelli HC;Guarino BD;Kanugula AK;Adapala R K;Perera V;Smith MA;Paruchuri S;Thodeti CK
Journal of Cellular Physiology
2020
2020-10-20
journalArticle
<a href="http://doi.org/10.1002/jcp.30116" target="_blank" rel="noreferrer noopener">10.1002/jcp.30116</a>
Validation of Quick Cognitive Screen
Casacchia Anthony; Ahmad Sobia; Drost Jennifer; Fosnight S; Gothard David
Journal of Pain and Symptom Management
2020
2020-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a class="doi" href="https://doi.org/10.1016/j.jpainsymman.2019.12.313" target="_blank" title="Persistent link using digital object identifier" rel="noreferrer noopener">10.1016/j.jpainsymman.2019.12.313</a>
Microglia depletion rapidly and reversibly alters amyloid pathology by modification of plaque compaction and morphologies.
Microglia; Inflammation; Neuroprotection; AD; Barrier; CSF1R; Plaques
Alzheimer's disease (AD) is a prominent neurodegenerative disorder characterized by deposition of β-amyloid (Aβ)-containing extracellular plaques, accompanied by a microglial-mediated inflammatory response, that leads to cognitive decline. Microglia perform many disease-modifying functions such as phagocytosis of plaques, plaque compaction, and modulation of inflammation through the secretion of cytokines. Microglia are reliant upon colony-stimulating factor receptor-1 (CSF1R) activation for survival. In AD mouse models, chronic targeted depletion of microglia via CSF1R antagonism attenuates plaque formation in early disease but fails to alter plaque burden in late disease. It is unclear if acute depletion of microglia during the peak period of plaque deposition will alter disease pathogenesis, and if so, whether these effects are reversible upon microglial repopulation. To test this, we administered the CSF1R antagonist PLX5622 to the 5XFAD mouse model of AD at four months of age for approximately one month. In a subset of mice, the drug treatment was discontinued, and the mice were fed a control diet for an additional month. We evaluated plaque burden and composition, microgliosis, inflammatory marker expression, and neuritic dystrophy. In 5XFAD animals, CSF1R blockade for 28 days depleted microglia across brain regions by over 50%, suppressed microgliosis, and reduced plaque burden. In microglial-depleted AD animals, neuritic dystrophy was enhanced, and increased diffuse-like plaques and fewer compact-like plaques were observed. Removal of PLX5622 elicited microglial repopulation and subsequent plaque remodeling, resulting in more compact plaques predominating microglia-repopulated regions. We found that microglia limit diffuse plaques by maintaining compact-like plaque properties, thereby blocking the progression of neuritic dystrophy. Microglial repopulation reverses these effects. Collectively, we show that microglia are neuroprotective through maintenance of plaque compaction and morphologies during peak disease progression.
Casali BT; MacPherson KP; Reed-Geaghan EG; Landreth GE
Neurobiology of Disease
2020
2020-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1016/j.nbd.2020.104956" target="_blank" rel="noreferrer noopener">10.1016/j.nbd.2020.104956</a>
Enteral and parenteral nutrition considerations in pediatric patients
compounding; enteral; neonatal; nutrition; parenteral; pediatric; stability
October 2019 Update
PURPOSE: Current clinical practice guidelines on management of enteral nutrition (EN) and parenteral nutrition (PN) in pediatric patients are reviewed. SUMMARY: The provision of EN and PN in pediatric patients poses many unique considerations and challenges. Although indications for use of EN and PN are similar in adult and pediatric populations, recommended EN and PN practices differ for pediatric versus adult patients in areas such as selection of EN and PN formulations, timing of EN and PN initiation, advancement of nutrition support, and EN and PN goals. Additionally, provision of EN and PN to pediatric patients poses unique compounding and medication administration challenges. This article provides a review of current EN and PN best practices and special nutrition considerations for neonates, infants, and other pediatric patients. CONCLUSION: The provision of EN and PN to pediatric patients presents many unique challenges. It is important for pharmacists to keep current with pediatric- and neonatal-specific guidelines on nutritional management of various disease states, as well as strategies to address compounding and medication administration challenges, in order to optimize EN and PN outcomes.
Cober Mary Petrea; Gura Kathleen M
American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists
2019
2019-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1093/ajhp/zxz174" target="_blank" rel="noreferrer noopener">10.1093/ajhp/zxz174</a>
The effect of an interprofessional pain service on nonmalignant pain control.
chronic pain; pain management; pharmacist; medication therapy management; opioid
PURPOSE: The primary objective of this project is to evaluate an existing interprofessional, nonmalignant pain service by measuring the difference in patient pain scores (numeric rating scale-11) before and after a pharmacist-led pain education class and medication therapy management (MTM) visit. Secondary objectives include determining the percentage of pharmacist recommendations approved, patient satisfaction, and difference in immediate release (IR) and extended release (ER) opioid use before and after enrollment. METHODS: Baseline data was obtained from a retrospective chart review. Enrolled patients attended an educational pain class with the pharmacist. At the MTM visit with the pharmacist 3-14 days after the initial education class, the patient's pain score was assessed along with his/her medication use and a care plan was developed and forwarded to the referring provider for implementation. Three months after the pain class and participation in the MTM visit, patients were contacted via phone to complete a survey. The survey questions assess patient satisfaction with the pain education program, their current pain score, and their knowledge of information covered during the pain class. RESULTS: Patients reported an average pre-enrollment pain score of 8.3/10 (n = 39) and a post-survey pain score of 5.6/10 (n = 39). The IR opioid use averaged 19.7 morphine equivalent daily dose (MEDD) at enrollment and decreased by 40% to 11.8 MEDD. The provider approval rate of the pharmacist recommended interventions ranges from 80%-92% depending on the pre designated disease state category. CONCLUSION: An interprofessional, nonmalignant pain service including a pharmacist-led class resulted in a decrease in average pain scores and MEDD in an underserved population.
Coffey Cory P; Ulbrich Timothy R; Baughman Kristin R; Awad Magdi H
American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
2019
2019-03
<a href="http://doi.org/10.1093/ajhp/zxy084" target="_blank" rel="noreferrer noopener">10.1093/ajhp/zxy084</a>
effect of an interprofessional pain service on nonmalignant pain control.
chronic pain; chronic pain; DISCHARGE planning; HEALTH literacy; HEALTH occupations students; INTERDISCIPLINARY education; LENGTH of stay in hospitals; MEDICAL appointments & schedules; MEDICAL care; MEDICAL personnel & patient; MEDICAL protocols; MEDICAL records; MEDICAL referrals; MEDICALLY underserved persons; medication therapy management; MORPHINE; opioid; pain management; pain management; PAIN measurement; PATIENT education; PATIENT satisfaction; pharmacist; pharmacists; RETROSPECTIVE studies; SUBSTANCE abuse; SURVEYS; TELEPHONES; THERAPEUTIC use of narcotics
Purpose The primary objective of this project was to evaluate an existing interprofessional, nonmalignant pain service by measuring the difference in patient pain scores (numeric rating scale-11) before and after a pharmacist-led pain education class and medication therapy management (MTM) visit. Secondary objectives included determining the percentage of pharmacist recommendations approved, patient satisfaction, and difference in immediate release (IR) and extended release (ER) opioid use before and after enrollment. Methods Baseline data were obtained from a retrospective chart review. Enrolled patients attended an educational pain class with the pharmacist. At the MTM visit with the pharmacist 3–14 days after the initial education class, the patient's pain score was assessed along with his/her medication use, and a care plan was developed and forwarded to the referring provider for implementation. Three months after the pain class and participation in the MTM visit, patients were contacted via telephone to complete a survey. The survey questions assessed patient satisfaction with the pain education program, their current pain score, and their knowledge of information covered during the pain class. Results Patients reported an average preenrollment pain score of 8.3/10 (n = 39) and a post-survey pain score of 5.6/10 (n = 39). The IR opioid use averaged 19.7 morphine equivalent daily dose (MEDD) at enrollment and decreased by 40% to 11.8 MEDD. The provider approval rate of the pharmacist-recommended interventions ranged from 80% to 92%, depending on the predesignated disease state category. Conclusion An interprofessional, nonmalignant-pain service including a pharmacist-led class resulted in a decrease in average pain scores and MEDD in an underserved population. [ABSTRACT FROM AUTHOR]
Coffey Cory P; Ulbrich Timothy R; Baughman Kristin R; Awad Magdi H
American Journal of Health-System Pharmacy
2019
2019-06
<a href="http://doi.org/10.1093/ajhp/zxy084" target="_blank" rel="noreferrer noopener">10.1093/ajhp/zxy084</a>
Overcoming barriers confronting application of protein therapeutics in bone fracture healing.
Osteoporosis; Drug delivery; Implants; Bone regeneration; Osteoinductive proteins; Osteopenia
Bone fracture is a major contributor to debilitation and death among patients with bone diseases. Thus, osteogenic protein therapeutics and their delivery to bone have been extensively researched as strategies to accelerate fracture healing. To prevent morbidity and mortality of fractures, which occur frequently in the aging population, there is a critical need for development of first-line therapeutics. Bone morphogenic protein-2 (BMP-2) has been at the forefront of bone regeneration research for its potent osteoinduction, despite safety concerns and biophysiological obstacles of delivery to bone. However, continued pursuit of osteoinductive proteins as a therapeutic option is largely aided by drug delivery systems, playing an imperative role in enhancing safety and efficacy. In this work, we highlighted several types of drug delivery platforms and their biomaterials, to evaluate the suitability in overcoming challenges of therapeutic protein delivery for bone regeneration. To showcase the clinical considerations for each type of platform, we have assessed the most common route of administration strategies for bone regeneration, classifying the platforms as implantable or injectable. Additionally, we have analyzed the commonly utilized models and methodology for safety and efficacy evaluation of these osteogenic protein-loaded systems, to present clinical opinions for future directions of research in this field. It is hoped that this review will promote research and development of clinically translatable osteogenic protein therapeutics, while targeting first-line treatment status for achieving desired outcomes of fracture healing. Graphical abstract.
Czech T; Oyewumi MO
Drug delivery and Translational Research
2020
2020-08-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1007/s13346-020-00829-x" target="_blank" rel="noreferrer noopener">10.1007/s13346-020-00829-x</a>
Delivery Systems as Vital Tools in Drug Repurposing.
combination drugs; drug delivery systems; drug development; nanocarriers; nanoparticles
The process of developing an old drug for new indications is now a widely accepted strategy of shortening drug development time, reducing drug costs, and improving drug availability, especially for rare and neglected diseases. In this mini-review, we highlighted the impact of drug delivery systems in the fulfillment of crucial aspects of drug repurposing such as (i) maximizing the repurposed drug effects on a new target, (ii) minimizing off-target effects, (iii) modulating the release profiles of drug at the site of absorption, (iv) modulating the pharmacokinetics/in vivo biodistribution of the repurposed drug, (v) targeting/modulating drug retention at the sites of action, and (vi) providing a suitable platform for therapeutic application of combination drugs.
Czech Tori; Lalani Reza; Oyewumi Moses O
AAPS PharmSciTech
2019
2019-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1208/s12249-019-1333-z" target="_blank" rel="noreferrer noopener">10.1208/s12249-019-1333-z</a>
Delivery Systems as Vital Tools in Drug Repurposing.
Humans; Nanoparticles; *Drug Delivery Systems; Nanoparticles; Tissue Distribution; combination drugs; *Drug Delivery Systems; drug development; nanocarriers; *Drug Repositioning; Drug Carriers
The process of developing an old drug for new indications is now a widely accepted strategy of shortening drug development time, reducing drug costs, and improving drug availability, especially for rare and neglected diseases. In this mini-review, we highlighted the impact of drug delivery systems in the fulfillment of crucial aspects of drug repurposing such as (i) maximizing the repurposed drug effects on a new target, (ii) minimizing off-target effects, (iii) modulating the release profiles of drug at the site of absorption, (iv) modulating the pharmacokinetics/in vivo biodistribution of the repurposed drug, (v) targeting/modulating drug retention at the sites of action, and (vi) providing a suitable platform for therapeutic application of combination drugs.
Czech Tori; Lalani Reza; Oyewumi Moses O
AAPS PharmSciTech
2019
2019-02
<a href="http://doi.org/10.1208/s12249-019-1333-z" target="_blank" rel="noreferrer noopener">10.1208/s12249-019-1333-z</a>
ASPEN Consensus Recommendations for Refeeding Syndrome.
magnesium; potassium; consensus; phosphorus; nutrition assessment; nutrition support; refeeding syndrome
INTRODUCTION: In the spring of 2017, the American Society for Parenteral and Enteral Nutrition (ASPEN) Parenteral Nutrition Safety Committee and the Clinical Practice Committee convened an interprofessional task force to develop consensus recommendations for identifying patients with or at risk for refeeding syndrome (RS) and for avoiding and managing the condition. This report provides narrative review and consensus recommendations in hospitalized adult and pediatric populations. METHODS: Because of the variation in definitions and methods reported in the literature, a consensus process was developed. Subgroups of authors investigated specific issues through literature review. Summaries were presented to the entire group for discussion via email and teleconferences. Each section was then compiled into a master document, several revisions of which were reviewed by the committee. FINDINGS/RECOMMENDATIONS: This group proposes a new clinical definition, and criteria for stratifying risk with treatment and screening strategies. The authors propose that RS diagnostic criteria be stratified as follows: a decrease in any 1, 2, or 3 of serum phosphorus, potassium, and/or magnesium levels by 10%-20% (mild), 20%-30% (moderate), or >30% and/or organ dysfunction resulting from a decrease in any of these and/or due to thiamin deficiency (severe), occurring within 5 days of reintroduction of calories. CONCLUSIONS: These consensus recommendations are intended to provide guidance regarding recognizing risk and identifying, stratifying, avoiding and managing RS. This consensus definition is additionally intended to be used as a basis for further research into the incidence, consequences, pathophysiology, avoidance, and treatment of RS.
da Silva Joshua S V; Seres David S; Sabino Kim; Adams Stephen C; Berdahl Gideon J; Citty Sandra Wolfe; Cober M Petrea; Evans David C; Greaves June R; Gura Kathleen M; Michalski Austin; Plogsted Stephen; Sacks Gordon S; Tucker Anne M; Worthington Patricia; Walker Renee N; Ayers Phil
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition
2020
2020-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1002/ncp.10474" target="_blank" rel="noreferrer noopener">10.1002/ncp.10474</a>
Examining targeted protein degradation from physiological and analytical perspectives: Enabling translation between cells and subjects.
The ability to target specific proteins for degradation may open a new door toward developing therapeutics. Although effort in chemistry is essential for advancing this modality, i.e., one needs to generate proteolysis targeting chimeras (bifunctional molecules, also referred to as PROTACS) or "molecular glues" to accelerate protein degradation, we suspect that investigations could also benefit by directing attention toward physiological regulation surrounding protein homeostasis, including the methods that can be used to examine changes in protein kinetics. This perspective will first consider some metabolic scenarios that might be of importance when one aims to change protein abundance by increasing protein degradation. Specifically, could protein turnover impact the apparent outcome? We will then outline how to study protein dynamics by coupling stable isotope tracer methods with mass spectrometry-based detection; since the experimental conditions could have a dramatic effect on protein turnover, special attention is directed toward the application of methods for quantifying protein kinetics using in vitro and in vivo models. Our goal is to present key concepts that should enable mechanistically informed studies which test targeted protein degradation strategies.
Daurio NA;Zhou H;Chen Y;Sheth PR;Imbriglio JE;McLaren DG;Tawa P;Rachdaoui N;Previs MJ;Kasumov T;O'Neil J;Previs SF
ACS Chemical Biology
2020
2020-09-30
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1021/acschembio.0c00380" target="_blank" rel="noreferrer noopener">10.1021/acschembio.0c00380</a>
An interprofessional case study competition addressing community healthcare needs and the opioid crisis
DeBoth Kelle K; Stoddard-Dare Patricia; Bruce Susan; Niederriter Joan
Journal of Interprofessional Education & Practice
2019
2019-06
<a class="doi" href="https://doi.org/10.1016/j.xjep.2019.03.007" target="_blank" title="Persistent link using digital object identifier" rel="noreferrer noopener">https://doi.org/10.1016/j.xjep.2019.03.007</a>
Shared mechanisms: osteoporosis and Alzheimer's disease?
Alzheimer's disease; dementia; osteoporosis; serotonin; Wnt
Dengler-Crish Christine M; Elefteriou Florent
Aging
2019
2019-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.18632/aging.101828" target="_blank" rel="noreferrer noopener">10.18632/aging.101828</a>
Shared mechanisms: osteoporosis and Alzheimer's disease?
Alzheimer's disease; dementia; osteoporosis; serotonin; Wnt
Dengler-Crish Christine M; Elefteriou Florent
Aging
2019
2019-02
<a href="http://doi.org/10.18632/aging.101828" target="_blank" rel="noreferrer noopener">10.18632/aging.101828</a>
Pharmacists' role in glycemic management in the inpatient setting: An opinion of the endocrine and metabolism practice and research network of the American College of Clinical Pharmacy.
Diabetes Mellitus; hyperglycemia; hypoglycemia; inpatients; pharmacists
The objective of this opinion paper was to identify and describe the role of pharmacists in ensuring safe and optimal management of patients with glycemic excursions in the inpatient setting. The role of the pharmacist includes involvement in admission medication history and reconciliation, formulary management of glucose‐lowering medications and devices, individual patient medication management, discharge transition of care, and interprofessional collaboration with other health care providers. Recommendations are based on review of published guidelines and literature focusing on the management of patients with hypo‐ and hyperglycemia in the hospital as well as during the time of transition to and from the inpatient setting. [ABSTRACT FROM AUTHOR]
Donihi Amy C; Moorman John M; Abla Alicia; Hanania Raja; Carneal Dustin; MacMaster Heidemarie Windham
JACCP: Journal of the American College of Clinical Pharmacy
2019
2019-04
<a href="http://doi.org/10.1002/jac5.1041" target="_blank" rel="noreferrer noopener">10.1002/jac5.1041</a>
Isotope Fractionation during Gas Chromatography Can Enhance Mass Spectrometry-Based Measures of (2)H-Labeling of Small Molecules.
stable isotopes; data integration; gas chromatography-mass spectrometry; isotope fractionation; metabolic flux; Savitzky-Golay
Stable isotope tracers can be used to quantify the activity of metabolic pathways. Specifically, (2)H-water is quite versatile, and its incorporation into various products can enable measurements of carbohydrate, lipid, protein and nucleic acid kinetics. However, since there are limits on how much (2)H-water can be administered and since some metabolic processes may be slow, it is possible that one may be challenged with measuring small changes in isotopic enrichment. We demonstrate an advantage of the isotope fractionation that occurs during gas chromatography, namely, setting tightly bounded integration regions yields a powerful approach for determining isotope ratios. We determined how the degree of isotope fractionation, chromatographic peak width and mass spectrometer dwell time can increase the apparent isotope labeling. Relatively simple changes in the logic surrounding data acquisition and processing can enhance gas chromatography-mass spectrometry measures of low levels of (2)H-labeling, this is especially useful when asymmetrical peaks are recorded at low signal:background. Although we have largely focused attention on alanine (which is of interest in studies of protein synthesis), it should be possible to extend the concepts to other analytes and/or hardware configurations.
Downes DP; Kasumov T; Daurio NA; Wood NB; Previs MJ; Sheth PR; McLaren DG; Previs SF
Metabolites
2020
2020-11-20
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.3390/metabo10110474" target="_blank" rel="noreferrer noopener">10.3390/metabo10110474</a>
Adaption of Geriatric Education Model Across Sites: Does Group Size Matter?
Geriatrics & Gerontology
2019 Annual Scientific Meeting of the American-Geriatrics-Society (AGS)
Drost J; Brown D K; Joan N; Sanders M; Fosnight S; Hazelett S; Kropp D
Journal of the American Geriatrics Society
2019
2019-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
n/a
Using Telehealth to Expand Community-based Care Manager Interdisciplinary Team Reach
Drost J; Fosnight S; Nauer T; Bring-Mazurek N; Morgan A; Chrzanowski B; Gareri M; Hazelett S; Kropp D
Journal of the American Geriatrics Society
2020
2020-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
n/a
Age And Pathology-related Changes In Neuron Density In The Chimpanzee Cortex
Anthropology; Evolutionary Biology
Edler M K; Munger E L; Hof P R; Hopkins W D; Ely J J; Erwin J M; Meindl R S; Mufson E J; Sherwood C C; Raghanti M A
American Journal of Physical Anthropology
2019
2019-03
Journal Article or Conference Abstract Publication
n/a
The role of the bile acid receptor TGR5 in Alzheimer's Disease
Ferrell JM;Boehme S;Gilliland T;Lin Li;Dengler-Crish CM;Takahashi S;Gonzalez FJ;Chiang JYL
Hepatology
2020
2020-11
journalArticle
<a href="http://doi.org/" target="_blank" rel="noreferrer noopener"></a>
Intrastriatal injection of alpha-synuclein preformed fibrils results in cognitive dysfunction and L-DOPA reversible sensorimotor impairments in rats
Fleming S;Patterson J;Yan L;Kemp C;Miller K;Stoll A;Duffy M;Herman D;Lipton J;Luk K;Goudreau J;Sortwell C
Movement Disorders
2020
2020-09
journalArticle
<a href="http://doi.org/" target="_blank" rel="noreferrer noopener"></a>
A Novel High Risk Medication Tool for Falls in Older Adults
Fosnight S; Hazelett S; Kropp D; Gareri M; Lehotsky K; Harvan A; Sanders M; Drost J
Journal of the American Geriatrics Society
2020
2020-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
n/a
Effects of pharmacy interventions at transitions of care on patient outcomes.
discharge medication reconciliation; length of stay; medication adherence; medication errors; pharmacists; readmissions
PURPOSE: An interdisciplinary group developed a care transitions process with a prominent pharmacist role. METHODS: The new transitions process was initiated on a 32-bed medical/surgical unit. Demographics, reconciliation data, information on medication adherence barriers, medication recommendations, and time spent performing interventions were prospectively collected for 284 consecutive patients over 54 days after the pharmacy participation was completely implemented. Outcome data, including 30-day readmission rates and length of stay, were retrospectively collected. RESULTS: When comparing metrics for all intervention patients to baseline metrics from the same months of the previous year, the readmission rate was decreased from 21.0% to 15.3% and mean length of stay decreased from 5.3 days to 4.4 days. Further improvement to a 10.2% readmission rate and a 3.6-day average length of stay were observed in the subgroup of intervention patients who received all components of the pharmacy intervention. Additionally, greater improvements were observed in intervention-period patients who received the full pharmacy intervention, as compared to those receiving only parts of the pharmacy intervention, with a 10.2-percentage-point lower readmission rate (10.2% vs 20.4%, P = 0.016) and a 1.7-day shorter length of stay (3.6 days vs. 5.3 days; 95% confidence interval, 0.814-2.68 days; P = 0.0003). For patients receiving any component of the pharmacy intervention, an average of 9.56 medication recommendations were made, with a mean of 0.89 change per patient deemed to be required to avoid harm and/or increased length of stay. CONCLUSION: A comprehensive pharmacy intervention added to a transitions intervention resulted in an average of nearly 10 medication recommendations per patient, improved length of stay, and reduced readmission rates.
Fosnight S; King Philip; Ewald Jacqueline; Feucht John; Lamtman Angela; Kropp D; Dittmer Alison; Sampson Jordan; Shah Morali
American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
2020
2020-05-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1093/ajhp/zxaa081" target="_blank" rel="noreferrer noopener">10.1093/ajhp/zxaa081</a>
Mechanistic complexities of bone loss in Alzheimer's disease: a review
Aging; Alzheimer’s; bone density; dementia; Osteoporosis
Purpose/Aim: Alzheimer's disease (AD), the primary cause of dementia in the elderly, is one of the leading age-related neurodegenerative diseases worldwide. While AD is notorious for destroying memory and cognition, dementia patients also experience greater incidence of bone loss and skeletal fracture than age-matched neurotypical individuals, greatly impacting their quality of life. Despite the significance of this comorbidity, there is no solid understanding of the mechanisms driving early bone loss in AD. Here, we review studies that have evaluated many of the obvious risk factors shared by dementia and osteoporosis, and illuminate emerging work investigating covert pathophysiological mechanisms shared between the disorders that may have potential as new risk biomarkers or therapeutic targets in AD. Conclusions: Skeletal deficits emerge very early in clinical Alzheimer's progression, and cannot be explained by coincident factors such as aging, female sex, mobility status, falls, or genetics. While research in this area is still in its infancy, studies implicate several potential mechanisms in disrupting skeletal homeostasis that include direct effects of amyloid-beta pathology on bone cells, neurofibrillary tau-induced damage to neural centers regulating skeletal remodeling, and/or systemic Wnt/Beta-catenin signaling deficits. Data from an increasing number of studies substantiate a role for the newly discovered "exercise hormone" irisin and its protein precursor FNDC5 in bone loss and AD-associated neurodegeneration. We conclude that the current status of research on bone loss in AD is insufficient and merits critical attention because this work could uncover novel diagnostic and therapeutic opportunities desperately needed to address AD.
Frame Gabrielle; Bretland Katie A; Dengler-Crish Christine M
Connective Tissue Research
2019
2019-06
<a href="http://doi.org/10.1080/03008207.2019.1624734" target="_blank" rel="noreferrer noopener">10.1080/03008207.2019.1624734</a>
Mechanistic complexities of bone loss in Alzheimer's disease: a review.
Aging; Alzheimer’s; bone density; dementia; osteoporosis
Purpose/Aim: Alzheimer's disease (AD), the primary cause of dementia in the elderly, is one of the leading age-related neurodegenerative diseases worldwide. While AD is notorious for destroying memory and cognition, dementia patients also experience greater incidence of bone loss and skeletal fracture than age-matched neurotypical individuals, greatly impacting their quality of life. Despite the significance of this comorbidity, there is no solid understanding of the mechanisms driving early bone loss in AD. Here, we review studies that have evaluated many of the obvious risk factors shared by dementia and osteoporosis, and illuminate emerging work investigating covert pathophysiological mechanisms shared between the disorders that may have potential as new risk biomarkers or therapeutic targets in AD. Conclusions: Skeletal deficits emerge very early in clinical Alzheimer's progression, and cannot be explained by coincident factors such as aging, female sex, mobility status, falls, or genetics. While research in this area is still in its infancy, studies implicate several potential mechanisms in disrupting skeletal homeostasis that include direct effects of amyloid-beta pathology on bone cells, neurofibrillary tau-induced damage to neural centers regulating skeletal remodeling, and/or systemic Wnt/Beta-catenin signaling deficits. Data from an increasing number of studies substantiate a role for the newly discovered "exercise hormone" irisin and its protein precursor FNDC5 in bone loss and AD-associated neurodegeneration. We conclude that the current status of research on bone loss in AD is insufficient and merits critical attention because this work could uncover novel diagnostic and therapeutic opportunities desperately needed to address AD.;
Frame Gabrielle; Bretland Katie A; Dengler-Crish Christine M
Connective Tissue Research
2019
2019-06
<a href="http://doi.org/10.1080/03008207.2019.1624734" target="_blank" rel="noreferrer noopener">10.1080/03008207.2019.1624734</a>
The role of the community pharmacist in veterinary patient care: A cross-sectional study of pharmacist and veterinarian viewpoints.
United States; Surveys and Questionnaires; Professional Role; Pharmacists; Counseling; Drug Compounding; Intersectoral Collaboration; Pharmacies; Veterinarians
BACKGROUND: The role of the community pharmacist is rapidly expanding to encompass the care of veterinary patients in the United States of America This change makes it imperative for pharmacists and veterinarians who practice in community settings to establish mutual agreement on the roles of pharmacists in the care of these patients. OBJECTIVE: To examine community-based pharmacist and veterinarian viewpoints on interprofessional collaboration and the role of the community pharmacist in veterinary patient care. METHODS: Cross-sectional surveys were sent to pharmacists and veterinarians who practice in a community setting in Ohio. Surveys collected demographic information and addressed the following themes: attitudes toward collaboration, perceived roles of the pharmacist, expectations of the pharmacist, and previous collaborative experiences. A chi-square test was used for statistical analysis. RESULTS: In total, 357 pharmacists and 232 veterinarians participated in the study. Both professions agreed that pharmacist-veterinarian collaboration is important in order to optimize veterinary patient care (chi-square (1, N=589)=7.7, p=0.006). Overall, veterinarians were more likely to identify an important role of the community pharmacist to be compounding medications (chi-square (1, N=589)=26.7, p<0.001) compared to counseling pet owners (chi-square (1, N=589)=171.7, p<0.001). Both groups reported similar levels of agreement regarding the importance for pharmacists to have adequate knowledge of veterinary medicine. CONCLUSIONS: Our study found that while both pharmacists and veterinarians conveyed a positive attitude regarding interprofessional collaboration, they disagreed on what role the pharmacist should play in the care of veterinary patients. Rectifying the discordant perceptions of these health care professionals may be critical to developing collaborative initiatives and optimizing veterinary patient care.
Fredrickson ME; Terlizzi H; Horne RL; Dannemiller S
Pharmacy Practice
2020
2020-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.18549/PharmPract.2020.3.1928" target="_blank" rel="noreferrer noopener">10.18549/PharmPract.2020.3.1928</a>
Efficacy of Tramadol for Pain Management in Patients Receiving Strong Cytochrome P450 2D6 Inhibitors
CYP2D6; cytochrome P450; drug interaction; pain control; tramadol
STUDY OBJECTIVE: Tramadol is metabolized by cytochrome P450 (CYP) 2D6 to form an active metabolite that exhibits its analgesic effect. Medications that inhibit this enzyme are used often in practice, yet the clinical impact of this interaction on the analgesic effects of tramadol has yet to be fully described. The objective was to determine whether a clinically relevant decrease in pain control is observed in patients taking scheduled tramadol concomitantly with a strong CYP2D6 inhibitor. DESIGN: Retrospective cohort study. SETTING: Large health care system. PATIENTS: One hundred fifty-two adult inpatients who received scheduled tramadol for at least 24 hours with (76 patients) or without (76 patients) a strong CYP2D6 inhibitor between January 1, 2012, and February 28, 2017, were included in the analysis. Patients hospitalized for opioid use disorder or those receiving substandard dosing of tramadol were excluded. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mean breakthrough opiate consumption in the presence and absence of CYP2D6 inhibitors. Secondary outcomes included mean pain scores, length of hospital stay, tramadol discontinuation rates, and prespecified subgroup analyses based on patient sex, race, and specific CYP2D6 inhibitor administered. Patients receiving concurrent CYP2D6 inhibitors required significantly more breakthrough morphine milligram equivalents per day compared with patients receiving scheduled tramadol without CYP2D6 inhibitors (geometric mean ± SD 18.2 ± 6.3 vs 5.7 ± 6.7 mg morphine milligram equivalents, p<0.001). No significant differences existed between cohorts for mean pain score, length of hospital stay, or tramadol discontinuation rate. CONCLUSION: This study demonstrated a clinically relevant decrease in the efficacy of tramadol when used for pain control in patients receiving a strong CYP2D6 inhibitor. These results should encourage clinicians to review medication lists for this interaction and adjust regimens accordingly to ensure adequate pain control.
Frost Derek A; Soric Mate M; Kaiser Ricky; Neugebauer Rachel E
Pharmacotherapy
2019
2019-06
<a href="http://doi.org/10.1002/phar.2269" target="_blank" rel="noreferrer noopener">10.1002/phar.2269</a>
Defining α-synuclein species responsible for Parkinson disease phenotypes in mice
alpha-synuclein (a-synuclein); amyloid; cytotoxicity; fibril; Lewy Body; motor behavior defect; neurodegenerative disease; oligomer; Parkinson disease; protein aggregation
Parkinson disease (PD) is a neurodegenerative disorder characterized by fibrillar neuronal inclusions composed of aggregated α-synuclein. These inclusions are associated with behavioral and pathological PD phenotypes. One strategy for therapeutic interventions is to prevent the formation of these inclusions in order to halt disease progression. α-Synuclein exists in multiple structural forms, including disordered, non-amyloid oligomers, ordered amyloid oligomers, and fibrils. It is critical to understand which conformers contribute to specific PD phenotypes. Here, we utilized a mouse model to explore the pathological effects of stable amyloid β-sheet oligomers compared with those of fibrillar α-synuclein. We biophysically characterized these species with transmission EM, atomic-force microscopy, CD spectroscopy, FTIR spectroscopy, analytical ultracentrifugation, and thioflavin T assays. We then injected these different α-synuclein forms into the mouse striatum to determine their ability to induce PD-related phenotypes. We found that β-sheet oligomers produce a small but significant loss of dopamine neurons in the substantia nigra pars compacta (SNc). Injection of small β-sheet fibril fragments, however, produced the most robust phenotypes, including reduction of striatal dopamine terminals, SNc loss of dopamine neurons, and motor behavior defects. We conclude that although the β-sheet oligomers cause some toxicity, the potent effects of the short fibrillar fragments can be attributed to their ability to recruit monomeric α-synuclein and spread in vivo and hence contribute to the development of PD-like phenotypes. These results suggest that strategies to reduce the formation and propagation of β-sheet fibrillar species could be an important route for therapeutic intervention in PD and related disorders.
Froula Jessica M; Castellana-Cruz Marta; Anabtawi Nadia M; Camino José D; Chen Serene W; Thrasher Drake R; Freire Jennifer; Yazdi Allen A; Fleming Sheila; Dobson Christopher M; Kumita Janet R; Cremades Nunilo; Volpicelli-Daley Laura A
The Journal of Biological Chemistry
2019
2019-05
<a href="http://doi.org/10.1074/jbc.RA119.007743" target="_blank" rel="noreferrer noopener">10.1074/jbc.RA119.007743</a>
Defining α-synuclein species responsible for Parkinson's disease phenotypes in mice.
DOPAMINERGIC neurons; FOURIER transform infrared spectroscopy; MOUSE diseases; PARKINSON'S disease; SPECIES; SUBSTANTIA nigra
Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar neuronal inclusions composed of aggregatedβ-synuclein (β-syn). These inclusions are associated with behavioral and pathological PD phenotypes. One strategy for therapeutic interventions is to prevent the formation of these inclusions to halt disease progression. β-Synuclein exists in multiple structural forms, including disordered, nonamyloid oligomers, ordered amyloid oligomers, and fibrils. It is critical to understand which conformers contribute to specific PD phenotypes. Here, we utilized a mouse model to explore the pathological effects of stable α-amyloid-sheet oligomers compared with those of fibrillar β-synuclein. We biophysically characterized these species with transmission EM, atomic-force microscopy, CD spectroscopy, FTIR spectroscopy, analytical ultracentrifugation, and thioflavin T assays. We then injected these different β-synuclein forms into the mouse striatum to determine their ability to induce PD-related phenotypes. We found thatα-sheet oligomers produce a small but significant loss of dopamine neurons in the substantia nigra pars compacta (SNc). Injection of small α-sheet fibril fragments, however, produced the most robust phenotypes, including reduction of striatal dopamine terminals, SNc loss of dopamine neurons, and motor-behavior defects. We conclude that although theα-sheet oligomers cause some toxicity, the potent effects of the short fibrillar fragments can be attributed to their ability to recruit monomeric β-synuclein and spread in vivo and hence contribute to the development of PD-like phenotypes. These results suggest that strategies to reduce the formation and propagation ofα-sheet fibrillar species could be an important route for therapeutic intervention in PD and related disorders. [ABSTRACT FROM AUTHOR]
Froula Jessica M; Castellana-Cruz Marta; Anabtawi Nadia M; Camino José D; Chen Serene W; Thrasher Drake R; Freire Jennifer; Yazdi Allen A; Fleming Sheila; Dobson Christopher M; Kumita Janet R; Cremades Nunilo; Volpicelli-Daley Laura A
Journal of Biological Chemistry
2019
2019-07
<a href="http://doi.org/10.1074/jbc.ra119.007743" target="_blank" rel="noreferrer noopener">10.1074/jbc.ra119.007743</a>
Developmental exposure to the organochlorine pesticide dieldrin causes male-specific exacerbation of α-synuclein-preformed fibril-induced toxicity and motor deficits.
Sex differences; Neuroinflammation; Parkinson's; Neurotoxicity; Pesticide; PARKINSON'S disease; SUBSTANTIA nigra; Synuclein; CORN oil; ORGANOCHLORINE pesticides; SALINE injections
Human and animal studies have shown that exposure to the organochlorine pesticide dieldrin is associated with increased risk of Parkinson's disease (PD). Previous work showed that developmental dieldrin exposure increased neuronal susceptibility to MPTP toxicity in male C57BL/6 mice, possibly via changes in dopamine (DA) packaging and turnover. However, the relevance of the MPTP model to PD pathophysiology has been questioned. We therefore studied dieldrin-induced neurotoxicity in the α-synuclein (α-syn)-preformed fibril (PFF) model, which better reflects the α-syn pathology and toxicity observed in PD pathogenesis. Specifically, we used a "two-hit" model to determine whether developmental dieldrin exposure increases susceptibility to α-syn PFF-induced synucleinopathy. Dams were fed either dieldrin (0.3 mg/kg, every 3–4 days) or vehicle corn oil starting 1 month prior to breeding and continuing through weaning of pups at postnatal day 22. At 12 weeks of age, male and female offspring received intrastriatal α-syn PFF or control saline injections. Consistent with the male-specific increased susceptibility to MPTP, our results demonstrate that developmental dieldrin exposure exacerbates PFF-induced toxicity in male mice only. Specifically, in male offspring, dieldrin exacerbated PFF-induced motor deficits on the challenging beam and increased DA turnover in the striatum 6 months after PFF injection. However, male offspring showed neither exacerbation of phosphorylated α-syn aggregation (pSyn) in the substantia nigra (SN) at 1 or 2 months post-PFF injection, nor exacerbation of PFF-induced TH and NeuN loss in the SN 6 months post-PFF injection. Collectively, these data indicate that developmental dieldrin exposure produces a male-specific exacerbation of synucleinopathy-induced behavioral and biochemical deficits. This sex-specific result is consistent with both previous work in the MPTP model, our previously reported sex-specific effects of this exposure paradigm on the male and female epigenome, and the higher prevalence and more severe course of PD in males. The novel two-hit environmental toxicant/PFF exposure paradigm established in this project can be used to explore the mechanisms by which other PD-related exposures alter neuronal vulnerability to synucleinopathy in sporadic PD. Unlabelled Image • Developmental dieldrin exposure increases α- syn -PFF-induced motor deficits. • Developmental dieldrin exposure increases PFF-induced deficits in DA handling. • Developmental dieldrin exposure does not affect PFF-induced loss of nigral neurons. • This is a novel paradigm modeling how environmental factors increase risk of PD. • Female mice show PFF-induced pathology, but no PFF-induced motor deficits. [ABSTRACT FROM AUTHOR]
Gezer AO; Kochmanski J; VanOeveren SE; Cole-Strauss A; Kemp CJ; Patterson JR; Miller KM; Kuhn NC; Herman DE; McIntire A; Lipton JW; Luk KC; Fleming SM; Sortwell CE; Bernstein AI
Neurobiology of Disease
2020
2020-07-15
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1016/j.nbd.2020.104947" target="_blank" rel="noreferrer noopener">10.1016/j.nbd.2020.104947</a>