Echinacea alkamide disposition and pharmacokinetics in humans after tablet ingestion

Echinacea is a widely used herbal remedy for the treatment of colds and other infections. However, almost nothing is known about the disposition and pharmacokinetics of any of its components, particularly the alkamides and caffeic acid conjugates which are thought to be the active phytochemicals. In this investigation, we have examined serial plasma samples from 9 healthy volunteers who ingested echinacea tablets manufactured from ethanolic liquid extracts of Echinacea angustifolia and Echinacea purpurea immediately after a standard high fat breakfast. Caffeic acid conjugates could not be identified in any plasma sample at any time after tablet ingestion. Alkamides were rapidly absorbed and were measurable in plasma 20 min after tablet ingestion and remained detectable for up to 12 h. Concentration-time curves for 2,4-diene and 2-ene alkamides were determined. The maximal concentrations for the sum of alkamides in human plasma were reached within 2.3 h post ingestion and averaged 336 +/- 131 ng eq/mL plasma. No obvious differences were observed in the pharmacokinetics of individual or total alkamides in 2 additional fasted subjects who took the same dose of the echinacea preparation. This single dose study provides evidence that alkamides are orally available and that their pharmacokinetics are in agreement with the one dose three times daily regimen already recommended for echinacea.

Ventilatory responses of healthy subjects to intravenous combinations of morphine and oxycodone under imposed hypercapnic and hypoxaemic conditions

Aims Previous isobolographic analysis revealed that coadministration of morphine and oxycodone produces synergistic antinociception in laboratory rodents. As both opioids can produce ventilatory depression, this study was designed to determine whether their ventilatory effects were synergistic when coadministered to healthy human subjects. Methods A placebo-controlled, randomized, crossover study was performed in 12 male volunteers. Ventilatory responses to hypoxaemia and hypercapnia were determined from 1-h intravenous infusions of saline ('placebo'), 15 mg morphine sulphate (M), 15 mg oxycodone hydrochloride (O), and their combination in the dose ratios of 1 : 2, 1 : 1, 2 : 1. Drug and metabolite concentrations in serial peripheral venous blood samples were measured by high-performance liquid chromatography-MS/MS. Results 'Placebo' treatment was without significant ventilatory effects. There were no systematic differences between active drug treatments on either the slopes or intercepts of the hypoxaemic and hypercapnia ventilation responses. During drug treatment, the mean minute ventilation at PETCO2 = 55 mmHg (V-E55) decreased to 74% of the subjects' before treatment values (95% confidence interval 62, 87), 68% (57, 80), 69% (59, 79), 68% (63, 73), and 61% (52, 69) for M15, M10/O5, M7.5/O7.5, M5/O10 and O15, respectively. Recovery was more prolonged with increasing oxycodone doses, corresponding to its greater potency and lower clearance compared with morphine. Conclusions Although adverse ventilatory effects of these drugs were found as expected, no unexpected or disproportionate effects of any of the morphine and oxycodone treatments were found that might impede their use in combination for pain management.

The effect of exercise on large artery haemodynamics in healthy young men

Background Brachial blood pressure predicts cardiovascular outcome at rest and during exercise. However, because of pulse pressure amplification, there is a marked difference between brachial pressure and central (aortic) pressure. Although central pressure is likely to have greater clinical importance, very little data exist regarding the central haemodynamic response to exercise. The aim of the present study was to determine the central and peripheral haemodynamic response to incremental aerobic exercise. Materials and methods Twelve healthy men aged 31 +/- 1 years (mean +/- SEM) exercised at 50%, 60%, 70% and 80% of their maximal heart rate (HRmax) on a bicycle ergometer. Central blood pressure and estimated aortic pulse wave velocity, assessed by timing of the reflected wave (T-R), were obtained noninvasively using pulse wave analysis. Pulse pressure amplification was defined as the ratio of peripheral to central pulse pressure and, to assess the influence of wave reflection on amplification, the ratio of peripheral pulse pressure to nonaugmented central pulse pressure (PPP : CDBP-P-1) was also calculated. Results During exercise, there was a significant, intensity-related, increase in mean arterial pressure and heart rate (P < 0.001). There was also a significant increase in pulse pressure amplification and in PPP : CDBP-P-1 (P < 0.001), but both were independent of exercise intensity. Estimated aortic pulse wave velocity increased during exercise (P < 0.001), indicating increased aortic stiffness. There was also a positive association between aortic pulse wave velocity and mean arterial pressure (r = 0.54; P < 0.001). Conclusions Exercise significantly increases pulse pressure amplification and estimated aortic stiffness.

Papillomavirus in healthy skin of Australian animals

Papillomaviruses are a group of ubiquitous viruses that are often found in normal skin of humans, as well as a range of different vertebrates. In this study, swab samples collected from the healthy skin of 225 Australian animals from 54 species were analysed for the presence of papillomavirus DNA with the general skin papillomavirus primer pair FAP59/FAP64. A total of five putative and potential new animal papillomavirus types were identified from three different animal species. The papillomaviruses were detected in one monotreme and two marsupial species: three from koalas, and one each from an Eastern grey kangaroo and an echidna. The papillomavirus prevalence in the three species was 14% (10/72) in koalas, 20% (1/5) in echidnas and 4% (1/23) in Eastern grey kangaroos. Phylogenetic analysis was performed on the putative koala papillomavirus type that could be cloned and it appears in the phylogenetic tree as a novel putative papillomavirus; genus. The data extend the range of species infected by papillomaviruses to the most primitive mammals: the monotremes and the marsupials.

Comparison of virulence gene profiles of Escherichia coli strains isolated from healthy and diarrheic swine

A combination of uni- and multiplex PCR assays targeting 58 virulence genes (VGs) associated with Escherichia coli strains causing intestinal and extraintestinal disease in humans and other mammals was used to analyze the VG repertoire of 23 commensal E. coli isolates from healthy pigs and 52 clinical isolates associated with porcine neonatal diarrhea (ND) and postweaning diarrhea (PWD). The relationship between the presence and absence of VGs was interrogated using three statistical methods. According to the generalized linear model, 17 of 58 VGs were found to be significant (P < 0.05) in distinguishing between commensal and clinical isolates. Nine of the 17 genes represented by iha, hlyA, aidA, east1, aah, fimH, iroN(E).(coli), traT, and saa have not been previously identified as important VGs in clinical porcine isolates in Australia. The remaining eight VGs code for fimbriae (F4, F5, F18, and F41) and toxins (STa, STh, LT, and Stx2), normally associated with porcine enterotoxigenic E. coli. Agglomerative hierarchical algorithm analysis grouped E. coli strains into subclusters based primarily on their serogroup. Multivariate analyses of clonal relationships based on the 17 VGs were collapsed into two-dimensional space by principal coordinate analysis. PWD clones were distributed in two quadrants, separated from ND and commensal clones, which tended to cluster within one quadrant. Clonal subclusters within quadrants were highly correlated with serogroups. These methods of analysis provide different perspectives in our attempts to understand how commensal and clinical porcine enterotoxigenic E. coli strains have evolved and are engaged in the dynamic process of losing or acquiring VGs within the pig population.