Post-Exercise Hypotension: An Alternative Management Strategy for Hypertension and Cardiovascular Disease?

Cardiovascular disease (CVD), including hypertension, is a leading cause of death worldwide and imposes an enormous burden on our societies [...

Stability of Compounded Topical Nifedipine in Cream, Gel, and Ointment Bases.

The objective of this study was to investigate the stability of compounded nifedipine cream in gel and ointment formulations dispensed in white plastic and glass amber jars. Extemporaneously compounded nifedipine cream (Glaxal Base), gel (K-Y Jelly), and ointment (Aquaphor) in white plastic and glass amber jars were stored at 4°C, 23°C, and 40°C. We determined potency on days 0, 7, 14, 30, 60, and 90, and subsequently assigned beyond-use-dates based on United States Pharmacopeia recommendations, organoleptic properties, and pH changes.

Drug-release Assessment of Compounded Topical Nifedipine and Diltiazem in Commonly Used Bases for Wound Healing.

The objective of this study was to determine release profiles of extemporaneously compounded nifedipine and diltiazem in commonly used bases in pharmacy practice. Release of nifedipine 0.2%, 2%, and 10% (w/w) from Glaxal Base, K-Y Jelly, and Aquaphor Healing Ointment, and of diltiazem 2% (w/w) from GlaxalBase, hydroxyethyl cellulose-based gel, and white petrolatum was quantified using the Franz-cell diffusion system.

Stability of Compounded Diltiazem Hydrochloride in Cream, Ointment, and Gel Formulations for Topical Use.

Interest in the topical use of compounded diltiazem has increased. Published information on the stability of such products is scarce. The objective of this study was to investigate the stability of diltiazem hydrochloride compounded in cream (Glaxal Base), ointment (white petrolatum), and hydroxyethyl cellulose-based gel over 90 days at room (23°C), refrigerator (4°C), and elevated (40°C) temperatures, stored in white plastic and glass amber containers.

Hemodynamic Assessment and In vivo Catabolism of Adenosine 5'-triphosphate in Doxorubicin or Isoproterenol-induced Cardiovascular Toxicity.

Objective: Previous studies have shown that catabolism of adenosine 5'-triphosphate (ATP) in systemic blood is a potential surrogate biomarker for cardiovascular toxicity. We compared the acute toxicity of high doses of doxorubicin (DOX) and isoproterenol (ISO) on hemodynamics and ATP catabolism in the systemic circulation.

Methods: sprague Dawley (SD) rats (n = 8 - 11) were each given either a single dose of 30 mg/kg ISO, or a twice-daily dose of 10 mg/kg of DOX or 4 doses of normal saline (control) by subcutaneous injection.

Compounded Topical Amitriptyline for Neuropathic Pain: In Vitro Release from Compounding Bases and Potential Correlation with Clinical Efficacy.

Background: Topical amitriptyline has been described as having mixed clinical efficacy for neuropathic pain. A few case reports using higher concentrations of this compound found clinical benefit, but many of these studies did not describe the components used in formulating the amitriptyline preparations.

Objective: To generate reproducible clinical measures of the characteristics of amitriptyline diffusion from selected compounding bases, to support a scientific approach to base selection when compounding this drug for neuropathic pain.

Compounded gabapentin for neuropathic pain: Stability and beyond-use date (BUD) in some commonly used bases.

Objectives: To investigate the stability and beyond-use date (BUD) of topical gabapentin in 3 commonly used bases.

Methods: Lipoderm cream, Versabase gel, and Emollient cream were used to compound gabapentin (10%). The products were stored in Ecolojars, kept at 25°C, 4°C, and 40°C, and samples were collected on different days (days 0, 14, 28, and 90).

ATP in red blood cells as biomarker for sepsis in humans.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection. Due to the lack of causative immune treatment, mortality of sepsis remains at a high level and represents one of the main disease burdens globally. Adenosine 5' triphosphate (ATP) levels in red blood cells (RBC) are modulated by various factors during sepsis, including a decrease in ATP production, an increase in ATP catabolism and alterations in ATP release.

Adenosine 5'-Triphosphate Metabolism in Red Blood Cells as a Potential Biomarker for Post-Exercise Hypotension and a Drug Target for Cardiovascular Protection.

The importance of adenosine and ATP in regulating many biological functions has long been recognized, especially for their effects on the cardiovascular system, which may be used for management of hypertension and cardiometabolic diseases. In response to ischemia and cardiovascular injury, ATP is broken down to release adenosine. The effect of adenosine is very short lived because it is rapidly taken up by erythrocytes (RBCs), myocardial and endothelial cells, and also rapidly catabolized to oxypurine metabolites.

Adenosine and Adenosine 5'-triphosphate Catabolism in Systemic Blood as a Potential Biomarker for Doxorubicin Cardiotoxicity in an Experimental Rat Model in vivo.

Background: Previous studies have shown that metabolism of adenosine 5'-triphosphate (ATP) in systemic blood is a potential surrogate biomarker for cardiovascular toxicity.

Objective: To investigate the acute effect of high dose of doxorubicin (DOX) on adenosine and ATP catabolism in systemic blood in vivo.

Method: Sprague Dawley (SD) rats were each given either 10 mg/kg of DOX (n = 8) or normal saline (1 mL/kg, n = 11) twice daily for 4 doses by subcutaneous (sc) injection.

Metabolomics and Biomarkers for Drug Discovery.

Metabolomics and biomarkers are increasingly used in drug discovery and development, and are applied to personalized medicine. Progress in these research areas has increased our understanding of disease pathology and improved therapeutic strategies for many diseases with unmet challenges. Further advances will ultimately result in the development of better drugs and breakthrough therapies, which will benefit millions of patients suffering from chronic and life-threatening diseases worldwide.

Doxorubicin impairs cardiomyocyte viability by suppressing transcription factor EB expression and disrupting autophagy.

Doxorubicin (DOX) is an effective anti-cancer agent. However, DOX treatment increases patient susceptibility to dilated cardiomyopathy. DOX predisposes cardiomyocytes to insult by suppressing mitochondrial energy metabolism, altering calcium flux, and disrupting proteolysis and proteostasis.

Effect of Cardiovascular Injury on Catabolism of Adenosine and Adenosine 5-'Triphosphate in Systemic Blood in a Freely Moving Rat Model In Vivo.

Background: Previous studies have shown that catabolism of adenosine 5'-triphosphate (ATP) in red blood cell (RBC) may be a key factor for cardiovascular protection and maintaining cardiovascular homeostasis.

Objective: To investigate the effect of cardiovascular injury on adenosine and ATP catabolism in systemic blood using a freely moving rat model in vivo.

Method: After acclimatized to the experimental environment, Sprague Dawley (SD) rats were each given either isoproterenol (30 mg/kg) or saline (1 mL/kg) by subcutaneous (sc) injection.

A Pilot Study to Assess Adenosine 5'-triphosphate Metabolism in Red Blood Cells as a Drug Target for Potential Cardiovascular Protection.

Objective: To study the effect of exercise preconditioning on adenosine 5'triphosphate (ATP) metabolism in red blood cells and cardiovascular protection against injury induced by isoproterenol in vivo.

Methods: Male Sprague Dawley rats (SDR) were each exercised on a treadmill for 15 minutes at 10 m/min and 10% grade (n = 7) (LowEx), or 14 m/min and 22% grade (n = 8) (VigEx). Two hours after the exercise, each rat received a single dose of isoproterenol (30 mg/kg) by subcutaneous (sc) injection.

Diltiazem reduces mortality and breakdown of ATP in red blood cell induced by isoproterenol in a freely moving rat model in vivo.

The benefit of calcium channel blockers for cardiovascular prevention against heart attack and stroke has not been firmly supported. We investigated the possible cardiovascular protective effect of diltiazem (DTZ) against injury induced by isoproterenol using a freely moving rat model in vivo. Sprague Dawley rats were injected subcutaneously (sc) with either 5 or 10 mg/kg of DTZ, or saline as control, twice daily for five doses.

Cytoprotective potential of anti-ischemic drugs against chemotherapy-induced cardiotoxicity in H9c2 myoblast cell line.

To investigate potential prevention or attenuation of anti- cancer drug induced cardiotoxicity using anti-ischemic drugs, a rat myoblast (H9c2) cell line was used as our in vitro cardiac model. Irinotecan and doxorubicin were found to be cytotoxic for the H9c2 cell line with IC50 of 30.69 ± 6.

Effect of acute exercise on cardiovascular hemodynamic and red blood cell concentrations of purine nucleotides in hypertensive compared with normotensives rats.

Objective: The mechanisms of exercise-induced health benefits are complex and not fully understood. This study investigated the effects of exercise and hypertension on cardiovascular hemodynamic responses and red blood cell (RBC) concentrations of purine nucleotides using normotensive and hypertensive rat models in vivo.

Methods: Sprague Dawley rats (SDRs) and spontaneously hypertensive rats (SHRs) were exercised on a treadmill for 15 min at a speed of 10 m/min and 5% grade.

Comparing pharmacokinetics and metabolism of diltiazem in normotensive Sprague Dawley and Wistar Kyoto rats vs. spontaneously hypertensive rats in vivo.

Background: In order to identify a suitable rodent model for preclinical study of calcium antagonists, the pharmacokinetics and metabolism of one of the prototypes diltiazem (DTZ) in normotensive Sprague Dawley (SDR) was compared with Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) following 5 mg/kg twice daily for five doses given by subcutaneous injection.

Methods: Pharmacokinetic data were analyzed by standard procedures assuming a one-compartment model with first-order input using Rstrips(®), and differences between the groups were considered significant when p<0.05.

Exercise improves hemodynamic profiles and increases red blood cell concentrations of purine nucleotides in a rodent model.

Objective: To study the effect of exercise on hemodynamic profiles and red blood cell (RBC) concentrations of adenosine-5'-triphosphate (ATP).

Methods: Male Sprague-Dawley (SD) rats (n = 9) were exercised on a treadmill for 15 min at a speed of 10 m/min with a 5% gradient after an hour settling down in a restrainer. Blood samples were collected via an indwelling carotid artery catheter using a 'Stopping Solution' from each rat before, during and after exercise.

Cladribine inhibits a diltiazem-induced increase in red blood cell purine nucleotide concentrations in a zebrafish model.

Minimizing drug interactions is paramount to improving the efficacy and tolerability of cancer therapy. The zebrafish represents an innovative cancer model due to highly conserved genetics and inherent capacity for high-throughput chemical screening. This pilot study extends the utility of the zebrafish to a preclinical model for pharmacodynamics by examining the interaction of the nucleoside analogue, cladribine with the calcium channel blocker, diltiazem.

Permeation of losartan across human respiratory epithelium: an in vitro study with Calu-3 cells.

The potential for nasal delivery of losartan, a drug with poor oral bioavailability, was investigated using Calu-3 cells. Epithelial permeation of the drug with or without dimethyl-beta-cyclodextrin (DM-beta-CD) and glycocholate was investigated. Possible transport mechanism of the compound and epithelial mucosal tolerance were screened.

Pharmacokinetics and metabolism of diltiazem following multiple doses: comparing normotensive rat vs. hypertensive rat models in vivo.

In order to identify a suitable rodent model for preclinical study of calcium antagonists, pharmacokinetics and metabolism of diltiazem (DTZ) were compared in normotensive SD and hypertensive SHR rat models following multiple doses (5 mg/kg twice daily for 5 doses). Plasma concentrations of DTZ and its major metabolites appeared to be higher in the SHR than the SD rats, although the differences did not reach statistical significance (p > 0.05).

HPLC assay with UV detection for determination of RBC purine nucleotide concentrations and application for biomarker study in vivo.

ATP and other purine nucleotides are important biomarkers for ischemia and may have considerable potential as targets for management of ischemic heart disease and stroke. The main objective of the study is to develop a rapid HPLC assay, which has adequate sensitivity and specificity for measuring concentrations of ATP, ADP, AMP, GTP, GDP and GMP in erythrocytes (RBC). The assays used ion-pair chromatography coupled with ultraviolet detection at 254 nm to separate and detect the purine nucleotides.

Pharmacokinetics of cladribine in a rat model following subcutaneous and intra-arterial injections.

Male Sprague Dawley rats (n = 6-8 per group) weighing from 300-450 g were used for the study. Each rat received a single dose of cladribine (CdA) by ia (1 mg/kg) or s.c.

Development and validation of a sensitive and specific HPLC assay of cladribine for pharmacokinetics studies in rats.

Purpose: To develop and validate a sensitive and specific HPLC assay for cladribine (CdA) in plasma for pharmacokinetic studies in rats.

Methods: CdA and the internal standard AZT were purchased from Sigma-Aldrich Chem. The HPLC system consisted of a Shimadzu LC-9A pump, a 3 im, 250 x 2.