betadex and Cardiovascular-Diseases

Long-term use of nonsteroidal anti-inflammatory drugs, including selective and nonselective cyclooxygenase inhibitors, has been suggested to be associated with cardiovascular (CV) safety risks. Data are limited regarding CV risks associated with short-term nonsteroidal anti-inflammatory drug use, including injectable formulations, although it has been suggested that even a single dose may increase CV adverse event (AE) risk. The objective of this study was to examine the CV safety of an injectable diclofenac formulation solubilized with hydroxypropyl-β-cyclodextrin (HPβCD) when given for ≤5days postoperatively.. A pooled analysis of CV AEs from 2 pivotal phase III clinical trials examining the efficacy and safety of intravenous (IV) HPβCD-diclofenac vs placebo and the active comparator ketorolac was conducted.. Postoperative, with treatment initiated in the postanesthesia care unit ≤6hours postsurgery.. Overall, 608 abdominal/pelvic and orthopedic surgery patients met inclusion criteria and received ≥1 study medication dose.. Patients received either HPβCD-diclofenac, ketorolac, or placebo via IV bolus injection every 6hours, for ≤5days postsurgery.. CV AEs, reported by study investigators, were evaluated through the treatment period and follow-up (≤37days after last study medication dose), and relative CV AE risks were estimated.. IV HPβCD-diclofenac was not associated with increased treatment-emergent CV AE incidence vs placebo (11.6% vs 12.2%; relative risk, 0.96 [95% confidence interval, 0.56-1.62]). Serious CV AEs as well as treatment-related AEs were uncommon, and there were no reports of myocardial infarction or cerebrovascular accident. CV AEs were uncommon during the follow-up period, occurring in 1.3%, 0%, and 1.4% of patients in the HPβCD-diclofenac, ketorolac, and placebo groups, respectively.. Although a longer duration follow-up study in a larger patient population would expand our understanding of potential CV risks, the present analysis suggests that postoperative use of HPβCD-diclofenac does not present an added CV safety risk over placebo.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acute Pain; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Cardiovascular Diseases; Diclofenac; Double-Blind Method; Excipients; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pain, Postoperative; Young Adult

Topics: 5-Methoxytryptamine; beta-Cyclodextrins; Calorimetry, Differential Scanning; Cardiovascular Diseases; Cardiovascular System; Glycerol; Humans; Membranes, Artificial; Microscopy, Electron, Scanning; Peptides, Cyclic; Porosity; Spectroscopy, Fourier Transform Infrared; Tissue Engineering; Tissue Scaffolds; X-Ray Diffraction

The application of cyclodextrins in food technology is extensive due to their unique ability to form complexes with many bioactive substances. Consumption of dairy products is associated with an increased risk of cardiovascular diseases (CVD) due to its high content of saturated fatty acids and cholesterol, so the production of low-cholesterol content products would be one of the critical steps in CVD prevention with regards to lowered total daily cholesterol intake. To maintain consumer acceptance, organoleptic profiles of such products should be, in the optimal case, the same with comparison to original ones. So, this study deals with the development of set low cholesterol foods (milk, cream, butter, soft cheese, cottage cheese) by β-cyclodextrin treatment and the characterization of their organoleptic profiles such as color and textural characteristics. During the experiments, high effectivity of cholesterol removal was reached as follows: milk-97.3%, cream-95.6%, butter-95.6%, cottage cheese-97.9%, soft cheese-97.7%, while color differences varied from 0.25 to 1.13 and textural characteristics were not influenced by cholesterol removal as well. So, it can be concluded that the proposed procedure is enabled to be substantial for the production of a new assortment of low-cholesterol dairy products with considerable health benefits toward the incidence of CVD.

Topics: Animals; beta-Cyclodextrins; Butter; Cardiovascular Diseases; Cheese; Cholesterol; Dairy Products; Humans; Milk

The aim of this study was to investigate the efficacy of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) as an antidotal treatment for the in vivo cardiovascular effects of amitriptyline poisoning. Experiments were carried out on 33 Wistar rats. To evaluate cardiovascular effects of HPBCD, rats were infused with dextrose or HPBCD. In the poisoning model, amitriptyline (0.94 mg/kg/min) was infused until the mean arterial blood pressure (MAP) dropped to 50 % of the baseline. Following amitriptyline infusion, dextrose, low-dose HPBCD (4.19 mg/kg/min), or high-dose HPBCD (16.76 mg/kg/min) was infused, and MAP, heart rate (HR), and electrocardiogram were recorded for 60 min. Hearts were examined for tissue damage and apoptosis. HPBCD infusion alone did not yield significant difference for MAP, HR, QRS duration, QT interval, and cardiac tissue damage when compared to dextrose (p > 0.05). In the poisoning model, MAP and HR decreased, while QRS duration and QT interval prolonged significantly following amitriptyline infusion (p < 0.0167). Dextrose, low-dose HPBCD, and high-dose HPBCD infusion similarly corrected MAP, HR, QRS duration, and QT interval values at the end-experiment time point (p > 0.05). Histological scores for tissue damage and apoptosis showed no significant difference between the groups (p > 0.05). Based on our results, HPBCD did not show cardiovascular toxicity, while it was not more effective than dextrose for the treatment of amitriptyline poisoning. Further antidotal studies of cyclodextrins with higher doses and/or binding affinities are needed for poisonings.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Amitriptyline; Animals; Antidotes; Apoptosis; Arterial Pressure; beta-Cyclodextrins; Cardiotoxicity; Cardiovascular Diseases; Chelating Agents; Disease Models, Animal; Electrocardiography; Glucose; Heart Rate; Hemodynamics; Male; Rats, Wistar; Time Factors

On the basis of the host-guest interactions between azobenzenes and cyclodextrins, a new strategy for the preparation of a dually functionalized poly(dimethylsiloxane) (PDMS) surface was investigated using surface-initiated atom-transfer radical polymerization (SI-ATRP) and click chemistry. The PDMS substrates were first oxidized in a H(2)SO(4)/H(2)O(2) solution to transform the surface Si-CH(3) groups into Si-OH groups. Then, the SI-ATRP initiator 3-(2-bromoisobutyramido)propyl(trime-thoxy)silane was grafted onto the substrates through a silanization reaction. Sequentially, the poly(ethylene glycol) (PEG) units were introduced onto the PDMS-Br surfaces via SI-ATRP reaction using oligo(ethylene glycol) methacrylate. Afterward, the bromide groups on the surface were converted to azido groups via nucleophilic substitution reaction with NaN(3). Finally, the azido-grafted PDMS surfaces were subjected to a click reaction with alkynyl and PEG-modified β-cyclodextrins, resulting in the grafting of cyclodextrins onto the PDMS surfaces. The composition and chemical state of the modified surfaces were characterized via X-ray photoelectron spectroscopy, and the stability and dynamic characteristics of the cyclodextrin-modified PDMS substrates were investigated via attenuated total reflection-Fourier transform infrared spectroscopy and temporal contact angle experiments. The surface morphology of the modified PDMS surfaces was characterized through imaging using a multimode atomic force microscope. A protein adsorption assay using Alexa Fluor594-labeled bovine serum albumin, Alexa Fluor594-labeled chicken egg albumin, and FITC-labeled lysozyme shows that the prepared PDMS surfaces possess good protein-repelling properties. On-surface studies on the interactions between azobenzenes and the cyclodextrin-modified surfaces reveal that the reversible binding of azobenzene to the cyclodextrin-modified PDMS surfaces and its subsequent release can be reversibly controlled using UV irradiation. Sandwich fluoroimmunoassay of the cardiac markers myoglobin and fatty acid-binding protein demonstrates that the cyclodextrin-modified PDMS surfaces can be repeatedly utilized in disease biomarker analysis.

Topics: Animals; Azo Compounds; beta-Cyclodextrins; Biomarkers; Cardiovascular Diseases; Cattle; Dimethylpolysiloxanes; Fatty Acid-Binding Proteins; Fluoroimmunoassay; Humans; Muramidase; Myoglobin; Organic Chemicals; Photoelectron Spectroscopy; Polyethylene Glycols; Serum Albumin, Bovine; Surface Properties