Structural characterisation and pharmacology of KHEYLRFamide (AF2) and KSAYMRFamide (PF3/AF8) from Haemonchus contortus

The FMRFamide-related peptides (FaRPs), KHEYLRFamide (AF2) and KSAYMRFamide (PF3) were structurally characterised from the parasitic nematode of sheep, Haemonchus contortus (MH isolate). Both peptides were sequenced in a single gas-phase sequencing run and their structure confirmed by mass spectrometry which identified peptides of 920 Da (C-terminally amidated AF2) and 902/918 Da (C-terminally amidated non-oxidised/oxidised PF3, respectively). AF2 had inhibitory effects on H. contortus muscle and inhibited acetylcholine (ACh, 10 mu M)-induced contractions, with a threshold for activity of I mu M. PF3 induced concentration-dependent contractions of H. contortus (activity threshold, 10 nM) and enhanced ACh contractions. Compared with the MH isolate, an isolate of H. contortus which has reduced sensitivity to cholinergic drugs (Lawes isolate) was less sensitive to the effects of PF3. The concentration-response curves for the cholinergic compounds ACh and levamisole (LEV), and PF3, but not a control, KPNFIRFamide (PF4), showed a statistically similar shift. This study implicates PF3 in the modulation of cholinergic function in H. contortus. (C) 1999 Elsevier Science B.V. All rights reserved.

Isolation, pharmacology and gene organization of KPSFVRFamide: A neuropeptide from Caenorhabditis elegans

To date, 53 peptides with C-terminal RFamides have been identified by the genome sequencing project in the nematode, Caenorhabditis elegans. In this study the FMRFamide-related peptide (FaRP) KPSFVRFamide (879.90 Da [MH](+)) was structurally characterized from extracts of the nematode, Caenorhabditis elegans. Two copies of KPSFVRFamide are encoded by a gene designated flp-9. RT-PCR identified a single cDNA product which was confirmed as flp-9 by sequence determination. Flp-9 cDNA was isolated from larval stages of C. elegans but was not detected-in adult worms, indicating that its expression is may be developmentally regulated. KPSFVRFamide displays sequence homology to the nematode peptide, KPNFIRFamide (PF4). The physiological effects of KPSFVRFamide, PF4 and the chimeras, KPNFVRFamide and KPSFIRFamide, were measured on body wall muscle and the vagina vera of the parasitic nematode, Ascaris suum. KPNFVRFamide and KPNFIRFamide had Cl--dependent inhibitory activity on innervated and denervated muscle-preparations, whereas KPSFVRFamide and KPSFIRFamide did not elicit a detectable physiological effect. Although all 4 peptides had inhibitory effects on the vagina vera, KPSFVRFamide and KPSFIRFamide (threshold, greater than or equal to 0.1 mu M) were less potent than KPNFVRFamide and KPNFIRFamide (threshold, greater than or equal to 10 nM). (C) 1999 Academic Press.

The pharmacology of nematode FMRFamide-related peptides

FMRFamide-related peptides (FaRPs) are the largest known family of invertebrate neuropeptides. Immunocytochemical screens of nematode tissues using antisera raised to these peptides have localized extensive FaRP-immunostaining to their nervous systems. Although 21 FaRPs have been isolated and sequenced from extracts of free-living and parasitic nematodes, available evidence indicates that other FaRPs await discovery. While our knowledge of the pharmacology of these native nematode neuropeptides is extremely limited, reports on their physiological activity in nematodes are ever increasing. All the nematode FaRPs examined so far have been found to have potent and varied actions on nematode neuromuscular activity. It is only through the extensive pharmacological and physiological assessment of the tissue, cell and receptor interactions of these peptidic messengers that an understanding of their activity on nematode neuromusculature will be possible. In this review, Aaron Maule and colleagues examine the current understanding of the pharmacology of nematode FaRPs.

Relationship between electrical resistivity and basic geotechnical parameters for marine clays

Recently, considerable efforts have been made in the attempt to map quick clay areas using electrical resistivity measurements. However there is a lack of understanding regarding which soil parameters control the measured resistivity values. To address this issue, inverted resistivity values from 15 marine clay sites in Norway have been compared with basic geotechnical index properties. It was found that the resistivity value is strongly controlled by the salt content of the pore fluid. Resistivity decreases rapidly with increasing salt content. There is also a relatively clear trend of decreasing resistivity with increasing clay content and plasticity index. Resistivity values become very low (˜5 O·m) for high clay content (>50%), medium- to high-plasticity (Ip ˜ 20%) materials with salt content values greater than about 8 g/L (or corresponding remoulded shear strength values greater than 4 kPa). For the range of values studied, there is poor correlation between resistivity and bulk density and between resistivity and water content. The data studied suggest that the range of resistivity values corresponding to quick clay is 10 to 100 O·m, which is consistent with other published limits. A comparison is made between two-dimensional electrical resistivity tomography (ERT) and resistivity cone penetration test (RCPTU) data for two of the sites and the two sets of data show similar trends and values irrespective of scale effect.

A feasibility study on the development and integration of a teaching aid for pharmacology

Traditional methods of teaching and learning in higher education are ever-evolving. This report assesses the feasibility of developing a teaching aid for pharmacology modules. Focus groups were established to gauge student and staff opinions on the use of teaching aids and an extensive literature review was conducted. The study identifies and critically evaluates a range of possibilities that could be developed and discusses practical issues such as accessibility, inclusion and assessment, associated with these potential aids. This initial study concludes that a suitable aid could take the form of a student-led development of a wiki-type website resource that included access to case-studies giving students ‘real-life’ experience of the concepts being studied. This type of project requires considerable time and financial support; nevertheless, this idea could be extended for many drugs and could be used in any health science course.

Effervescent and standard formulations of ranitidine--a comparison of their pharmacokinetics and pharmacology

An effervescent formulation of ranitidine may be absorbed faster and achieve a faster onset of action than conventional tablet form. The aim of this study was to compare the effects of effervescent formulations of ranitidine with equivalent dose standard tablets, in terms of intragastric pH and plasma pharmacokinetics in the initial 6 h following dosing.

Digoxin toxicity in the aged. Characterising and avoiding the problem

Digoxin is one of the most frequently prescribed drugs, particularly in the elderly population where there is an increased prevalence of atrial fibrillation and cardiac failure. The drug has a narrow therapeutic range and has gained a reputation for producing adverse effects in older patients. The more frail elderly patients with coexistent disease, often taking other treatments, are more at risk from digoxin toxicity due to inappropriate dosing, noncompliance, or increased sensitivity to digoxin resulting from pharmacokinetic or pharmacodynamic interactions. Application of basic pharmacological principles may be helpful in anticipating these problems. Elderly patients more commonly receive digoxin than younger patients, which in part accounts for the higher rates of toxicity in this group. Numerous components contribute to the development of toxicity, and diagnosis of toxicity is difficult in this age group. The measurement of serum concentrations can contribute to the clinical diagnosis. A major problem is the accurate diagnosis of digoxin toxicity which may have numerous nonspecific clinical manifestations, many of which are related to coexisting disease in elderly patients. This diagnostic imprecision is well recognised but has been helped by the introduction of serum digoxin measurement. However, reliance on serum concentrations should not replace clinical judgement, since these do not always correlate with toxicity. The apparently decreasing incidence of toxicity over recent years probably reflects several factors: the improvement in digoxin formulations, awareness of digoxin pharmacology, utilisation of serum concentrations, and the realisation that digoxin withdrawal is a viable proposition in elderly patients. Greater knowledge about the causes and prevention of digoxin toxicity should further reduce the morbidity and mortality arising from digoxin overdose, especially in the elderly population.

Reconsidering Resource Rights: The Case for a Basic Right to the Benefits of Life-Sustaining Ecosystem Services

In the presence of anthropogenic climate change, gross environmental degradation, and mass abject poverty, many political theorists currently debate issues such as people's right to water, the right to food, and the distribution of rights to natural resources more generally. However, thus far many theorists either focus (somewhat arbitrarily) only on one particular resource (e.g. water) or they treat all natural resources alike, meaning that many relevant distinctions within the group of natural resources are overlooked. Hence, the paper will start with an analysis of the various forms which natural resources can take and how this might influence one's conception of resource rights. In so doing, the paper argues that we have to carefully distinguish between the actual physical resources people might control and how we distribute these, and the life-sustaining benefits each and every person draws from sustainable and functioning ecosystems. Based on this distinction, the paper will argue for a right to the benefits of life-sustaining ecosystem services as a universal basic right every person has. Further distributive claims with respect to particular physical resources would thus be limited by the requirements of such a basic right.