Radiation Effects on Methamphetamine Pharmacokinetics and Pharmacodynamics in Rats.

BACKGROUND AND OBJECTIVES: Whole-body radiation exposure has been shown to alter the pharmacokinetics of certain drugs in both animal models and humans, but little is known about the effect of radiation on psychoactive medications. These drugs may have altered pharmacokinetics when administered during or after space travel or therapeutic or accidental radiation exposure, resulting in reduced efficacy or increased toxicity. METHODS: Methamphetamine was used to determine the effects of acutely administered 1, 3, and 6 Gy radiation on drug pharmacokinetics and pharmacodynamics. Male Wistar rats were exposed to 0, 1, 3, or 6 Gy X-ray radiation on day 0. The serum pharmacokinetics of subcutaneously administered 1 mg/kg methamphetamine was determined on day 3. Methamphetamine-induced (1 mg/kg) locomotor activity was measured on day 5. Brain methamphetamine concentrations were determined 2 h after methamphetamine administration (1 mg/kg) on day 6. Renal and hepatic serum biomarkers were assessed on days 3 and 6, with liver histology performed on day 6. RESULTS: While serum half-life and unchanged methamphetamine urine clearance were unaffected by any radiation dose, maximum methamphetamine concentrations and methamphetamine and amphetamine metabolite area under the serum concentration-time curve values from 0 to 300 min were significantly reduced after 6 Gy radiation exposure. Additionally, methamphetamine-induced locomotor activity and the brain to serum methamphetamine concentration ratio were significantly elevated after 6 Gy radiation. CONCLUSIONS: While 1-6 Gy radiation exposure did not affect methamphetamine elimination, 6 Gy exposure had effects on both subcutaneous absorption and brain distribution. These effects should be considered when administering drugs during or after radiation exposure.

Confronting the "Brutal Facts" and Identifying Opportunities as Pharmacy Education Weathers the COVID-19 Pandemic.

The COVID-19 pandemic has impacted almost every facet of modern life, causing almost a million deaths worldwide as well as widespread economic and social strife. While contemplating how we might emerge from this pandemic, we were reminded of the Stockdale paradox. We suggest that the Academy must not only confront the brutal facts of the current situation, but we must also maintain faith in the endgame and a commitment to prevail despite the enormous challenges we face. The Academy can play a key role in helping the world recover from this pandemic if we build on the diversity and strengths of our programs nationally and globally. We suggest that there are three key actions that pharmacists and pharmacy educators must take to show leadership in this time of need. First, we must be the voice that reassures the public about the value of science and the scientific method. Second, we must work locally and nationally to ensure an optimal public health response. Finally, members of the Academy must serve as role models with respect to the essential public health tools to prevent the spread of COVID-19. By remaining positive, keeping the endgame in mind, and confronting the most brutal facts of the COVID-19 pandemic, we are confident that pharmacy education and pharmacy will weather this storm and arise even stronger for it.

Exploring Dendrimer Nanoparticles for Chronic Wound Healing.

The United States spends billions of dollars to treat chronic wounds each year. Wound healing is complex in nature which involves several intricate multiphase processes that can be delayed for a number of reasons leading to the development of chronic wounds. Wound healing therapies range from topical preparations to surgical repair with treatment options that vary based on other underlying factors like co-infection, age, or co-morbidities such as diabetes. Historically, micelles and liposomes are some of the nanoparticle drug delivery systems explored to treat chronic wounds; however, recent data suggests that dendrimers have shown potential to rival these systems in treating chronic wounds as well as other diseases. This mini review examines advances in dendrimer nanoparticle drug delivery systems to treat chronic wounds.

Long-Term Treatment with Empagliflozin Attenuates Renal Damage in Obese Zucker Rat.

INTRODUCTION: Empagliflozin, a known inhibitor of sodium-glucose cotransporter type 2 (SGLT2) decreases glucose reabsorption by the renal tubules and promotes glucose excretion into the urine. While the effectiveness of Empagliflozin in the management of hyperglycemia along with associated cardiovascular and all-cause mortality has been demonstrated previously, the therapeutic benefits associated with the long-term use of this drug in obese animals have yet to be investigated. METHODS: Male 5-week-old lean and obese Zucker rats were randomly assigned to one of the 4 groups- lean control, lean treated, obese control, obese treated and treated with either Empagliflozin (10 mg/kg BW / day) or placebo for 25 weeks to investigate the therapeutic effect of Empagliflozin. RESULTS: Empagliflozin treatment in the obese animals was associated with decreased body weight, attenuated the loss of F-actin from the renal tubules and improved renal structure and function. These changes in renal function were associated with significant improvements in the glucose tolerance, and decreased non-fasting circulatory levels of glucose, amylase, and other inflammatory markers including NGAL, cystatin C, and clusterin. CONCLUSION: Long-term use of Empagliflozin in diabetic obese Zucker rats is associated with improvements in glucose tolerance and decreased loss of renal structure and function.

A review of the antimicrobial potential of precious metal derived nanoparticle constructs.

The field of nanotechnology is rapidly growing. The promise of pharmacotherapeutics emerging from this vast field has drawn the attention of many researchers. However, with the increase in the prevalence of antibiotic resistant microorganisms, the manifestations of these promises are needed now more than ever. Many have postulated the antimicrobial potential of nanoparticle constructs derived from precious metals/noble metals nanoparticles (NMNPs), such as silver nanoparticles that show activity against multidrug resistant bacteria. In this review we will evaluate the current studies and explore the data to obtain a clear picture of the potential of these particles and the validity of the claims of drug resistant treatments with NMNPs.

Spleen data: Cerium oxide nanoparticles attenuate polymicrobial sepsis induced spenic damage in male Sprague Dawley rats.

Sepsis is a serious life threatening medical emergency which, if not treated properly, oftentimes results in organ failure and death. Current sepsis treatment protocols are largely centered on the use of antibiotics and supportive care. Recent studies have suggested that antibiotics fail to be effective for sepsis treatment when administered during hypo-dynamic phase of sepsis that is usually characterized by the presence of a cytokine storm. As such, there is an urgent need to develop novel therapeutic drugs that target the inflammatory cytokines that are secreted as a result of increased reactive oxygen species. Cerium oxide nanoparticles (CeO2) have been shown to act as anti-inflammatory and anti-oxidant agent. More recently, they have been shown to attenuate polymicrobial insult-induced mortality in Sprague Dawley rats. Here, we investigated whether CeO2 nanoparticles can attenuate splenic damage in this animal model of sepsis. A single intravenous dose (0.5 mg/kg) of CeO2 nanoparticles attenuated the sepsis-induced loss in splenic cell structural integrity. These improvements in splenic structure were accompanied by a decrease in expression of late phase pro-inflammatory cytokine high mobility group box 1 (HMGB1) along with reduced bacterial load in the blood and peritoneal fluid of septic animals. Taken together these findings suggest that CeO2 nanoparticles can be used to attenuate polymicrobial insult-induced splenic damage in Sprague dawley rats.

High-frequency electrical stimulation (HFES) Data Lean and Obese Zucker Rat Soleus Muscle: Regulation of p70S6kinase Associated Proteins.

Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the AKT, GSK3beta, mTor, p70s6K, Pten, and Shp2 proteins in the lean and obese (fa/fa) Zucker rat soleus muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our lab (Katta et al., 2009a, 2009b; Tullgren et al., 1991) [1-3] and concurrent Data in Brief articles (Ginjupalli et al., 2017a, 2017b; Rice et al., 2017a, 2017b) [4-7].

Diabetic Zucker rat Tibialis anterior muscle high-frequency electrical stimulation (HFES) data: Regulation of MAPKs associated proteins.

Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK 1/2, p38, and JNK in the lean and obese (fa/fa) Zucker rat tibialus anterior (TA) muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our lab (Katta et al., 2009, Katta et al., 2009, Tullgren et al., 1991) [1-3] and concurrent Data in Brief articles (Ginjupalli et al., 2017, Rice et al., 2017, Rice et al., 2017, Rice et al., 2017) [4-7].

Lean and Obese Zucker Rat Extensor Digitorum Longus Muscle high-frequency electrical stimulation (HFES) Data: Regulation of MAPKs Associated Proteins.

Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK 1/2, p38, and JNK in the lean and obese (fa/fa) Zucker rat extensor digitorum longus (EDL) muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our (Katta et al., 2009a, 2009b, 2008) [1-3] and concurrent Data in Brief articles (Ginjupalli et al., 2017a, 2017b; Rice et al., 2017a, 2017b) [4-7].

High-frequency electrical stimulation (HFES) data lean and obese Zucker rat tibialis anterior muscle: Regulation of glycogen synthase kinase 3 beta (GSK3B) associated proteins.

Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the AMPK, GSK3beta, and Shp2 in the lean and obese (fa/fa) Zucker rat tibialis anterior (TA) muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our lab (Katta et al., 2009; Katta et al., 2009; Tullgren et al., 1991) [1-3] and concurrent Data in Brief articles (Ginjupalli et al., 2017; Rice et al., 2017; Rice et al., 2017; Rice et al., 2017) [4-7].

Lean and Obese Zucker Rat Extensor Digitorum Longus Muscle high-frequency electrical stimulation (HFES) Data: Regulation of p70S6kinase Associated Proteins.

Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the AKT, GSK3beta, mTor, p70s6K, Pten, and Shp2 in the lean and obese (fa/fa) Zucker rat Extensor Digitorum Longus (EDL) muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our lab (Katta et al., 2009a, 2009b; Tullgren et al., 1991) [1-3] and concurrent Data in Brief articles (Ginjupalli et al., 2017a, 2017b; Rice et al., 2017a, 2017b) [4-7].

Vascular mechanotransduction data in a rodent model of diabetes: Pressure-induced regulation of SHP2 and associated signaling in the rat inferior vena cava.

The effect of diabetes on vascular mechano-transductive response is of great concern. Given the higher rate of vein graft failures associated with diabetes, understanding the multiple cellular and molecular events associated with vascular remodeling is of vital importance. This article represents data related to a study published in Cardiovascular Diabetology [1] (Rice et al., 2006) and Open Journal of Endocrine and Metabolic Diseases [2] (Rice et al., 2015) evaluating the effect of pressurization on rat inferior venae cavae (IVC). Provided within this articles is information related to the method and processing of raw data related to our prior publish work and Data in Brief articles [3], [4] (Rice et al., 2017), as well as the evaluation of alternation in SHP-2 signaling and associated proteins in response to mechanical force. IVC from lean and obese animals were exposed to a 30 min perfusion of 120 mm Hg pressure and evaluated for changes in expression of SHP2, BCL-3, BCL-XL, HSP 27, HSP 70, and PI3K p85, along with the phosphorylation of SHP-2 (Tyr 542).

Predictors of student performance on the Pharmacy Curriculum Outcomes Assessment at a new school of pharmacy using admissions and demographic data.

OBJECTIVES: To characterize student performance on the Pharmacy Curriculum Outcomes Assessment (PCOA) and to determine the significance of specific admissions criteria and pharmacy school performance to predict student performance on the PCOA during the first through third professional years. METHODS: Multivariate linear regression models were developed to study the relationships between various independent variables and students' PCOA total scores during the first through third professional years. RESULTS: To date, four cohorts have successfully taken the PCOA examination. Results indicate that the Pharmacy College Admissions Test (PCAT), the Health Science Reasoning Test (HSRT), and cumulative pharmacy grade point average were the only consistent significant predictors of higher PCOA total scores across all students who have taken the exam at our school of pharmacy. CONCLUSION: The school should examine and clarify the role of PCOA within its curricular assessment program. Results suggest that certain admissions criteria and performance in pharmacy school are associated with higher PCOA scores.

Diabetes alters vascular mechanotransduction data: Pressure-induced regulation of mTor and associated signaling in the rat inferior vena cava.

Diabetes is a multifaceted disease with various etiologies. The complexity of this pathology creates a myriad of factors that must be considered when addressing surgical outcomes and prognosis. Of vital importance to cardiovascular surgery is the viability of homographic vein grafts. Due to the fact, diabetic patients have a higher rate of vein graph failure, a greater understanding of the effect diabetes has on vascular mechano-transductive response is critical to improving patient prognosis. This article represents data regarding a study published in Cardiovascular Diabetology (Rice et al., 2006) [1] and Open Journal of Endocrine and Metabolic Diseases (Rice et al., 2015) [2] with the purpose of evaluating the effect of pressurization on rat inferior venae cavae (IVC). Here we provide the information about the method and processing of raw data related to our prior publish work and Data in Brief articles (Rice et al., Submitted for publication) [3,4]. The data contained in this article evaluates the contribution of mTor signaling and associated proteins. IVC from lean and obese animals were exposed to a 30 min perfusion of 120 mm Hg pressure and evaluated for changes in expression and phosphorylation of mTor, p70s6k, GSK3ß, and 4EBP-1.

Diabetes alters vascular mechanotransduction data: Pressure-induced regulation of Nf-kapa-B p65 and translational associated signaling in the rat inferior vena cava.

Diabetic patients have a high rate of vein graft failure due to attrition or vessel occlusion that cause recurrent ischemic events or vein graft. Veins grafted into a high-pressure arterial environment must undergo vascular remodeling to better handle the altered hemodynamics and intravascular increased pressure. Multiple cellular and molecular events are purported to be associated with vascular remodeling of veins. Understanding the effect diabetes has on vascular mechano-transductive response is critical to decreasing graft failure rates. This article represents data regarding a study published in Cardiovascular Diabetology [1] and Open Journal of Endocrine and Metabolic Diseases [2] with the purpose of evaluating the effect of pressurization on rat inferior venae cavae (IVC). Here we provide the information about the method and processing of raw data related to our prior publish work and Data in Brief articles [3], [4]. The data contained in this article evaluates the contribution of NF-kB signaling and associated proteins. IVC from lean and obese animals were exposed to a 30 min of perfusion at 120 mm Hg pressure and evaluated for changes in expression and (IkB-alpha, NF-kB p50, NF-kB p105, NF-kB p65, Traf2, caspase 12), phosphorylation of (IkB-alpha (ser 32), Fox01 (ser 256), and Fox04 (ser 193)) proteins thought to be involved in the regulation of vascular mechanotransduction.

Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia Reperfusion Injury in Sprague Dawley Rats.

BACKGROUND: Hepatic ischemia reperfusion is one the main causes for graft failure following transplantation. Although, the molecular events that lead to hepatic failure following ischemia reperfusion (IR) are diverse and complex, previous studies have shown that excessive formation of reactive oxygen species (ROS) are responsible for hepatic IR injury. Cerium oxide (CeO2) nanoparticles have been previously shown to act as an anti-oxidant and anti-inflammatory agent. Here, we evaluated the protective effects of CeO2 nanoparticles on hepatic ischemia reperfusion injury. METHODS: Male Sprague Dawley rats were randomly assigned to one of the four groups: Control, CeO2 nanoparticle only, hepatic ischemia reperfusion (IR) group and hepatic ischemia reperfusion (IR) plus CeO2 nanoparticle group (IR+ CeO2). Partial warm hepatic ischemia was induced in left lateral and median lobes for 1h, followed by 6h of reperfusion. Animals were sacrificed after 6h of reperfusion and blood and tissue samples were collected and processed for various biochemical experiments. RESULTS: Prophylactic treatment with CeO2 nanoparticles (0.5mg/kg i.v (IR+CeO2 group)) 1 hour prior to hepatic ischemia and subsequent reperfusion injury lead to a decrease in serum levels of alanine aminotransaminase and lactate dehydrogenase at 6 hours after reperfusion. These changes were accompanied by significant decrease in hepatocyte necrosis along with reduction in several serum inflammatory markers such as macrophage derived chemokine, macrophage inflammatory protein-2, KC/GRO, myoglobin and plasminogen activator inhibitor-1. However, immunoblotting demonstrated no significant changes in the levels of apoptosis related protein markers such as bax, bcl2 and caspase 3 in IR and IR+ CeO2 groups at 6 hours suggesting necrosis as the main pathway for hepatocyte death. CONCLUSION: Taken together, these data suggest that CeO2 nanoparticles attenuate IR induced cell death and can be used as a prophylactic agent to prevent hepatic injury associated with graft failure.

Curcumin nanoparticles attenuate cardiac remodeling due to pulmonary arterial hypertension.

Herein, we investigate whether curcumin nanoparticles (Cur NPs) are effective for the treatment of monocrotaline (MCT)-induced pulmonary arterial hypertension in Sprague Dawley rat. Echocardiography was performed at the start of the study and 28 days after MCT injection. Compared to MCT only animals, Cur NP administration was associated with reduced right ventricular (RV) wall thickness and a decreased right ventricle weight/body weight ratio. Cur NPs also attenuated MCT induced increase in RV mRNA expression of TNF-α and IL-1ß. These changes were also associated with decreased RV expression of nitrotyrosine, fibronectin and myosin heavy chain-ß.

Cerium oxide nanoparticle treatment ameliorates peritonitis-induced diaphragm dysfunction.

The severe inflammation observed during sepsis is thought to cause diaphragm dysfunction, which is associated with poor patient prognosis. Cerium oxide (CeO2) nanoparticles have been posited to exhibit anti-inflammatory and antioxidative activities suggesting that these particles may be of potential use for the treatment of inflammatory disorders. To investigate this possibility, Sprague Dawley rats were randomly assigned to the following groups: sham control, CeO2 nanoparticle treatment only (0.5 mg/kg iv), sepsis, and sepsis+CeO2 nanoparticles. Sepsis was induced by the introduction of cecal material (600 mg/kg) directly into the peritoneal cavity. Nanoparticle treatment decreased sepsis-associated impairments in diaphragmatic contractile (P(o)) function (sham: 25.6±1.6 N/cm(2) vs CeO2: 23.4±0.8 N/cm(2) vs Sep: 15.9±1.0 N/cm(2) vs Sep+CeO2: 20.0±1.0 N/cm(2), P<0.05). These improvements in diaphragm contractile function were accompanied by a normalization of protein translation signaling (Akt, FOXO-1, and 4EBP1), diminished proteolysis (caspase 8 and ubiquitin levels), and decreased inflammatory signaling (Stat3 and iNOS). Histological analysis suggested that nanoparticle treatment was associated with diminished sarcolemma damage and diminished inflammatory cell infiltration. These data indicate CeO2 nanoparticles may improve diaphragmatic function in the septic laboratory rat.

Cerium oxide nanoparticles attenuate acute kidney injury induced by intra-abdominal infection in Sprague-Dawley rats.

BACKGROUND: Intra-abdominal infection or peritonitis is a cause for great concern due to high mortality rates. The prognosis of severe intra-abdominal infection is significantly diminished in the presence of acute kidney injury (AKI) which is often characterized by renal tubular cell death that can lead to renal failure. The purpose of the current study is to examine the therapeutic efficacy of cerium oxide (CeO2) nanoparticles for the treatment of peritonitis-induced AKI by polymicrobial insult. RESULTS: A one-time administration of CeO2 nanoparticles (0.5 mg/kg) in the absence of antibiotics or other supportive care, attenuated peritonitis-induced tubular dilatation and the loss of brush border in male Sprague-Dawley rats. These improvements in renal structure were accompanied by decreases in serum cystatin-C levels, reduced renal oxidative stress, diminished Stat-3 phosphorylation and an attenuation of caspase-3 cleavage suggesting that the nanoparticle treatment improved renal glomerular filtration rate, diminished renal inflammation and reduced renal apoptosis. Consistent with these data, further analysis demonstrated that the CeO2 nanoparticle treatment diminished peritonitis-induced increases in serum kidney injury molecule-1 (KIM-1), osteopontin, ß-2 microglobulin and vascular endothelial growth factor-A (VEGF-A) levels. In addition, the nanoparticle attenuated peritonitis-induced hyperglycemia along with increases in blood urea nitrogen (BUN), serum potassium and sodium. CONCLUSION: CeO2 nanoparticles scavenge reactive oxygen species and attenuate polymicrobial insult induced increase in inflammatory mediators and subsequent AKI. Taken together, the data indicate that CeO2 nanoparticles may be useful as an alternative therapeutic agent or in conjunction with standard medical care for the treatment of peritonitis induced acute kidney injury.

Cecal inoculum peritonitis: An alternative model for sepsis vascular dysfunction study.

AIMS: Sepsis is a life threatening condition that is characterized by the loss of vascular reactivity. The factor(s) responsible for the diminished vascular function seen in sepsis are not well understood. The purpose of this study was to characterize the vascular dysfunction from the rat cecal inoculum (CI) sepsis model using cecal ligation and puncture (CLP), and lipopolysaccharide (LPS) sepsis as reference models. MATERIALS AND METHODS: Experiments were performed on isolated aorta from CI, CLP and LPS treated rats using a combination of pharmacological approaches. KEY FINDINGS: Phenylephrine (PE)-induced aortic contraction was significantly decreased in each model (p<0.05) and not normalized by L-NAME or indomethacin. The vascular response elicited in the CI model for acetylcholine (Ach) was more similar to that seen in the CLP than the LPS model. The removal of the endothelial layer increased sensitivity to L-NAME (p<0.05) in aortae from CI group. Inhibition of the large conductance Ca(2+)/voltage sensitive K(+) (BKCa) channel did not normalize PE hyporesponsiveness but did abolish sepsis-induced contractile oscillation. Inhibition of the voltage dependent Kv1.5 channel was not able to reverse the vascular hyporesponsiveness, however, inhibition of the ATP dependent (KATP) channel inhibition partially restored the contractile response (p<0.05). Elevation of VCAM expression and aortic structural alternation were observed in each model. SIGNIFICANCE: These results suggest that the CI model may be an additional tool that could be used to investigate the mechanisms of vascular hyporesponsiveness in sepsis.