Drug targeting using low density lipoprotein (LDL): physicochemical factors affecting drug loading into LDL particles

Low density lipoprotein (LDL) has been found suitable as a targeting carrier for cytotoxic drugs. However, higher drug loading into LDL particles without disrupting their native integrity remains a major obstacle. The purpose of this study is to investigate the different physicochemical factors that may affect drug loading and to characterize LDL-drug conjugates. Doxorubicin (Dox) and 3', 5'-O-dipalmitoyl-5-iodo-2'-deoxyuridine (dpIUdR) were used as reference cytotoxic drugs. Drugs were loaded into LDL particles using the dry film method with or without surfactants, liposomal and the direct addition method. The effects of incubation temperature, time and stoichiometry of LDL-drug conjugates on drug loading were investigated. The LDL-drug conjugates were evaluated for their stability and characterized by differential scanning calorimetry (DSC), denatured gel (SDS-PAGE), and electron microscopy (EM). We have suitably incorporated 45+/-10 Dox and 150+/-25 dpIUdR molecules/LDL particle. A seven-fold increase in Dox incorporation was achieved with the liposomal preparation compared to the dry film method. A 4- to 6-h incubation at 37 degreesC was suitable to restore the native structure of LDL particles. No apo B fragmentation of LDL particles was noted on denatured gel. DSC studies showed no change in the Tm of the LDL and the LDL-drug conjugates. An increase in particle size of LDL-dpIUdR, not LDL-Dox was observed in EM compared to the native LDL which may be related to higher incorporation of dpIUdR. The results indicate that physicochemical factors significantly affect drug loading efficiency and may need to be considered to optimize drug incorporation into LDL particles.     

Comments on `A Lyapunov function of two-dimensional linear systems'

The authors show that the function introduced in the above-titled paper by H. Mahgoub and R. Carroll (ibid., vol. AC-31, p.170-172, (1986)) is not a Lyapunov function for a discrete 2-D system     

N-methyl-D-aspartate antagonists, glutamate release inhibitors, 4-aminopyridine at neuromuscular transmission

GLP-1, an incretin hormone of the enteroinsular axis with insulinotropic and glucagonostatic activity, is secreted after nutrient ingestion. GLP-1 is mainly produced by intestinal L-cells in the lower gastrointestinal tract (GIT); simple carbohydrates are absorbed in the upper GIT and alpha-glucosidase inhibition leads to augmented and prolonged GLP-1 release in normal subjects. In a cross-over study, 100 mg acarbose or placebo was administered simultaneously with 100 g sucrose to 11 hyperglycaemic Type 2 diabetic patients poorly controlled with diet and sulphonylureas. Plasma levels of GLP-1, insulin, C-peptide, glugacon, GIP, glucose and H2-exhalation were measured over 6 h. Differences in the integrated responses over the observation period were evaluated by repeated measurement analysis of variance with fasting values used as covariates. With acarbose, sucrose reached the colon 60-90 min after ingestion as indicated by a significant increment in breath hydrogen exhalation (p = 0.005). After an early GLP-1 increment 15 min after sucrose under both conditions, GLP-1 release was prolonged in the acarbose group (p = 0.001; significant from 210 to 360 min.). Initially (0-150 min), glucose (p = 0.001), insulin (p = 0.001), and GIP (p < 0.001) were suppressed by acarbose, whereas later there were no significant differences. Glucagon levels were higher with acarbose in the last 3 h of the 6 h observation period (p = 0.02). We conclude that in hyperglycaemic Type 2 diabetic patients, ingestion of acarbose with a sucrose load leads to elevated and prolonged GLP-1 release.     

An expert system to automate timing design

Presents a novel approach for automating the timing design of interfaces between VLSI chips in microcomputer systems. The Prolog-based expert system, called TDS (for timing design system), incorporates the heuristic knowledge of the hardware designer. TDS is a rule-based system that interprets the specification sheets of VLSI chips and can synthesize, diagnose, and verify timing charts at the expert's level. The system uses a functional model based on timing specifications, not the structural information. TDS can model other interfaces that are based on timing specifications, such as standard bus interfaces     

Strength and Frictional Properties of Popcorn Kernel as Affected by Moisture Content

Strength properties and dynamic coefficient of friction of popcorn kernels were evaluated as a function of moisture content in the range of 7.78–16.72 g/100 g dry solids. In order to determine strength properties of the kernels that are in terms of deformation at rupture point, rupture force, energy absorbed, hardness, and toughness of the popcorn kernels were quasi-statically loaded between two parallel plates. To determine frictional properties, friction tests were performed on aluminum, steel, and fiberglass surfaces. The values related to the strength properties, in general, decreased as the moisture content increased. On the other hand, the dynamic coefficient of friction of the popcorn kernels increased with increasing moisture content.     

Antimicrobial effect of PEG–PLA on food-spoilage microorganisms

Food Science and Biotechnology - Polyethylene glycol (PEG) and polyethylene glycol–polylactic acid (PEG–PLA) have an organic structure and no negative effect on human health. The...     

Tobacco craving predicts lapse to smoking among adolescent smokers in cessation treatment.

Previous research indicates that tobacco craving predicts relapse to smoking among adult smokers attempting to quit. We hypothesized a similar relationship between craving and lapse (any smoking following a period of abstinence) among adolescent smokers during the treatment phase of a clinical trial. A visit was considered a lapse visit if the participant reported smoking or had a carbon monoxide level of 7 ppm or greater subsequent to an abstinent visit. A total of 34 participants (mean age = 14.9 years [SD = 1.3]; mean cigarettes/day = 18.0 [SD = 7.6]; mean Fagerstr?m Test for Nicotine Dependence score = 6.8 [SD = 1.34]; 65% female), were included in the present analysis of 167 treatment visits. Logistic regression analyses showed a positive relationship between degree of craving, measured by the Questionnaire on Smoking Urges, and lapse during smoking cessation treatment (p = .013). Additionally, linear regression analyses demonstrated a strong positive association between cigarettes smoked per day and craving scores (p<.001). Taken together with other data, these findings suggest that degree of craving might influence tobacco abstinence for adolescent smokers. Thus monitoring and addressing craving appears useful to increase the success of adolescent smoking cessation.