L.H. du Plessis

Enhancement of nasal and intestinal calcitonin delivery by the novel Pheroid fatty acid based delivery system, and by N-trimethyl chitosan chloride.

Therapeutic peptides are highly potent and specific in their functions, but difficulties in their administration require parallel development of viable delivery systems to improve their bioavailability. In this study the potential of a novel lipid-based colloidal delivery system for improving the absorption of nasally and intestinally administered salmon calcitonin (sCT) was investigated. Two types of delivery vehicles based on Pheroid technology was prepared and characterized. Liposome-like bilayer vesicles had a mean diameter of 1.0 microm and microsponges were 1.6 microm. Doses of 10 IU/kg and 500 IU/kg bodyweight sCT were administered intranasally and intestinally to rats, respectively. The obtained absorption enhancement with Pheroid vesicles and Pheroid microsponges were also compared with the absorption enhancement obtained with N-trimethyl chitosan chloride (TMC). With the inclusion of 0.5% (w/v) TMC the maximum plasma concentration (C(max)) of sCT increased from 72.6+/-6.1 pg/ml to 478.5+/-6.1 pg/ml after nasal administration. Pheroid vesicles and Pheroid microsponges increased the C(max) values of sCT to 262.64+/-17.1 pg/ml and 202.66+/-28.6 pg/ml, respectively. The time to reach the maximum concentration (T(max)) was also significantly decreased from 35 min to approximately 14 min. Intestinal administration of Pheroid formulations increased the C(max) of sCT from 249.1+/-21.5 pg/ml to 386.2+/-45.5 and 432.1+/-18.9 pg/ml, respectively for Pheroid vesicles and Pheroid microsponges. TMC increased the C(max) of sCT to 738.9+/-277.1 pg/ml. TMC and Pheroid technology could offer the potential to significantly improve intranasal and intestinal absorption of sCT and reduce the variability in absorption.

DNA damage and repair detected by the comet assay in lymphocytes of African petrol attendants : a pilot study

Petrol attendants are exposed to petrol volatile organic compounds (VOCs) which may have genotoxic and carcinogenic effects. The single-cell gel electrophoresis assay (comet assay) is a method highly sensitive to DNA damage induced by environmental and occupational exposure to carcinogenic and mutagenic agents. The aim of this study was to evaluate the level of exposure of petrol attendants to petrol VOCs and also to determine their effect on DNA damage and repair in lymphocytes of African petrol attendants. The exposed group consisted of 20 subjects, randomly selected from three petrol stations. A control group of 20 unexposed subjects was also chosen and matched for age and smoking habits with the exposed group. Sorbent tubes were used to assess personal exposure of petrol attendants. The comet assay was used to investigate the basal DNA damage and repair capacity in isolated lymphocytes of petrol attendants and unexposed subjects. Blood samples were taken from the petrol attendants at the end of their 8-h working shift and also from the unexposed subjects. The petrol attendants were found to be exposed to levels of petrol VOCs lower than the South African occupational exposure limit for constituent chemicals. A significant relationship was found between the volume of petrol sold during the shift and the average concentrations of benzene, toluene and the total VOCs measured. However, relative humidity had a negative correlation with the average concentrations of benzene, toluene, xylene and the total VOCs. Significantly higher basal DNA damage was observed with the exposed group compared to the unexposed group. The period of exposure influenced the level of DNA damage and the calculated repair capacity. Smoking and age had a significant influence on the level of DNA damage. DNA repair capacity was delayed in smokers of both exposed and unexposed group.

In vivo/in vitro pharmacokinetic and pharmacodynamic study of spray-dried poly-(dl-lactic-co-glycolic) acid nanoparticles encapsulating rifampicin and isoniazid

Poly-(dl-lactic-co-glycolic) acid (PLGA) nanoparticles were prepared by a double emulsion solvent evaporation spray-drying technique and coated with polyethylene glycol (PEG 1% v/v). The PLGA nanoparticles had a small size (229±7.6 to 382±23.9nm), uniform size distribution and positive zeta potential (+12.45±4.53mV). In vitro/in vivo assays were performed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) performance of these nanoparticles following nanoencapsulation of the anti-tuberculosis drugs rifampicin (RIF) and isoniazid (INH). The results demonstrated the potential for the reduction in protein binding of these drugs by protection in the polymer core. Furthermore, in vitro efficacy was demonstrated using Mycobacterium tuberculosis (M. tb.) (strain H37Rv). Sustained drug release over seven days were observed for these drugs following once-off oral administration in mice with subsequent drug distribution of up to 10 days in the liver and lungs for RIF and INH, respectively. It was concluded by these studies combined with our previous reports that spray-dried PLGA nanoparticles demonstrate potential for the improvement of tuberculosis chemotherapy by nanoencapsulation of anti-tuberculosis drugs.

Evaluation of the physical properties and stability of two lipid drug delivery systems containing mefloquine

Stability data is used to determine the change the product has undergone over a certain time period at specific temperatures. In the present study, the physical stability characterized by size, pH and entrapment efficacy of mefloquine loaded liposomes and Pheroid™ vesicles were investigated. Size was accurately determined by flow cytometry. Entrapment efficacy, after unentrapped drug was removed was successfully determined by UV-spectrophotometry. The formulations contained 0.5% (m/v) mefloquine and results showed that mefloquine interfered with the formation of lipid bilayer of the liposomes. Liposomes increased in size from 5.22±0.03 μm to 9.71±1.11 μm with accelerated stability and large aggregates were observed. A notable difference in stability testing of Pheroid™ vesicles was seen with no significant increase in size. Entrapment efficacy of 68.72±0.04% (5°C), 67.45±2.92% (25°C) and 67.45±2.92% (30°C) were obtained at the different storage conditions. With these findings the mefloquine loaded Pheroid™ vesicles are stable and should be used investigated for the possible increase in efficacy and bioavailability and decrease toxicity.

The effect of blood ozonation on mitochondrial function and apoptosis of peripheral blood mononuclear cells in the presence and absence of plasma antioxidants

Ozone-autohemotherapy (O3-AHT) has recently gained interest as a form of alternative and complementary medicine. There is, however, some concern regarding its toxicity and effectiveness. Ozone is a powerful oxidant and when introduced into biological fluids react with most cellular components including proteins, lipids and DNA. We assessed the effect of O3-AHT on peripheral blood mononuclear cells (PBMC) viability, apoptosis and mitochondrial function in the presence and absence of plasma antioxidants. Exposure to ozone increased lactate dehydrogenase (LDH) release and caspase 3/7 activity in PBMC. A decrease in mitochondrial function was measured as a decrease in ATP levels and an increase in NADH/ NAD+ ratio. Complex IV (cytochrome c oxidase) of the respiratory chain was almost completely inhibited by ozone. These results indicated that the death of PBMC was probably through apoptosis. These effects were more evident in the absence of plasma antioxidants. Therefore, high concentrations of ozone were damaging to the cells, but this effect was diminished by antioxidants present in plasma. It is not certain if the in vitro damage will be propagated when ozonated blood is injected back into individuals. One must bear in mind that only a fraction of the total blood volume is ozonated.

Methods, measures and indicators for evaluating benefits of transportation research

Abstract The purpose of this article is to provide updated information by identifying and discussing methods, measures and indicators for evaluating benefits appropriate for transportation-related research facilities/programmes. The information has been drawn from within and outside transportation research. The article discusses the sources driving the need for evaluating benefits and describes the challenges confronting the evaluation process. It reviews and compares qualitative and quantitative techniques and highlights previous published work, investigations and case studies. Many traditional challenges of determining benefits persist, contributing to the gap between the ability to identify non-technical benefits of research and the growing need to demonstrate such benefits. This article aims to stimulate dialogue and investigations to advance the development of an appropriate robust method to determine quantitative benefits stemming from specifically accelerated pavement testing (APT) type transportation research. The ultimate goal is to help better understand, demonstrate and communicate the benefits of APT research.

Case Study for Evaluating Benefits of Pavement Research: Final Results

Heavy-duty pavement innovations developed through research for a major rehabilitation project in California were evaluated. The performance benefits of the innovations were examined, and the economic benefits from implementation of the pavement designs were analyzed. Benefits are presented through descriptions of the rehabilitation project, background on the development of long-life pavement rehabilitation innovations, and design requirements that limit permanent deformation (rutting) within the first 5 years of service. Results from field measurements confirmed that the innovative pavements met the performance criterion. The final results of a pilot study to quantify direct benefits stemming from accelerated pavement testing are presented. Cost–benefit analysis that included agency costs with and without road user costs was used, and the influence of the discount rate in net present value calculations is given. Road user costs had a significant influence on cost–benefit calculations, especially in the case of a heavily congested freeway. This influence led to cost savings ranging from

Topical delivery of selected growth factors

1.128 million to

Southern African scorpion toxins : An overview

121.570 million, which emphasized the importance of performing a sensitivity analysis instead of reporting a single estimate of savings and benefit–cost ratio. The final results showed clear field performance benefits of the pavement innovations and indicated positive economic benefits from the research that led to innovations.

Cysteine-free peptides in scorpion venom: geographical distribution, structure-function relationship and mode of action

The concept that the time to onset of erythema after the application of the rubefacient and urticant substance methyl nicotinate (MN) indicates skin barrier competence was introduced 30 years ago. MN produces a dose-dependent erythema on topical application to intact skin, the nature of which is known to be fast moving (in the order of minutes) and variable. Using tissue viability imaging (TiVi) the time course and degree of the reaction can be conveniently followed and analysed. Inter-individual variability can be quite marked but intra-individual variability is less pronounced. At the upper end of provocation (higher doses, more sensitive individuals) urtication can occur, which decreases blood flow by increasing pressure on and thus emptying capillaries. The TiVi system can quantitate urtication and inherent (blanched) skin colour. The utility of MN application in the study of individual barrier function and microvascular reactivity is increased by the use of the TiVi system for collection and analysis of data.