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.

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.

Surviving but stigmatised:Making sense of living with Burkholderia cepacia

Infection control policies recommend segregation of people with Cystic Fibrosis (CF) according to bacterial status. This involves isolating those people with cepacia from all other CF patients in order to prevent additional infection. These policies are reliant on the understanding and adherence of those colonised with cepacia. Service user reports suggest that emotions like anxiety and anger are aroused when those with cepacia are faced with cross infection measures (UK CF Trust, 2009). No studies to date investigate this anecdotal emotional reaction. This research was conducted to ask what it is like to live with cepacia, using in depth interviews. A phenomenological approach was used. Three themes that appeared to characterise the experience of living with cepacia were identified: (1) Lost Identity: cepacia can challenge one’s self identity, and along with cross infection measures lead to feeling objectified and even alienated from the CF group identity. (2) Status: Condemned: being colonised with cepacia brings with it knowledge of a certain type of restricted future, and an imagined death. There is loss of normality and hope. (3) I Am Cepacia: making decisions about preventing cross infection is influenced by medical knowledge as well as human emotions and social information; therefore adherence to these measures is fluid and contextual. These themes have real world clinical implications for all CF services, where preventing the spread of cepacia is paramount. Responsibility for cross infection is a burden and requires knowledge and understanding from both those living with and without cepacia. We need to see beyond the bacteria to the person.

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial: study protocol for a randomized controlled trial

Background: Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI.

Methods/Design: Patients fulfilling the American-European Consensus Conference Definition of ALI will be randomized in a 1: 1 ratio to receive enteral simvastatin 80 mg or placebo once daily for a maximum of 28 days. Allocation to randomized groups will be stratified with respect to hospital of recruitment and vasopressor requirement. Data will be recorded by participating ICUs until hospital discharge, and surviving patients will be followed up by post at 3, 6 and 12 months post randomization. The primary outcome is number of ventilator-free days to day 28. Secondary outcomes are: change in oxygenation index and sequential organ failure assessment score up to day 28, number of non pulmonary organ failure free days to day 28, critical care unit mortality; hospital mortality; 28 day post randomization mortality and 12 month post randomization mortality; health related quality of life at discharge, 3, 6 and 12 months post randomization; length of critical care unit and hospital stay; health service use up to 12 months post-randomization; and safety. A total of 540 patients will be recruited from approximately 35 ICUs in the UK and Ireland. An economic evaluation will be conducted alongside the trial. Plasma and urine samples will be taken up to day 28 to investigate potential mechanisms by which simvastatin might act to improve clinical outcomes.

The Developing Habitus of the Anti-Social Behaviour Practitioner: From Expansion in Years of Plenty to Surviving the Age of Austerity

Specialist anti-social behaviour units are common within social housing providers, with many established in response to the policies of the New Labour governments of 1997–2010. These units now find themselves operating in a different political and financial environment. Following the English riots of 2011, the Coalition government, whilst imposing budgetary cuts across the public sector, called on social housing providers to intensify their role in tackling disorder. This article explores the habitus or working cultures within anti-social behaviour units post-New Labour. It does so through empirical research conducted in the aftermath of the English riots. The research finds that practitioners view their work as a core function of social housing provision. They have developed an understanding of human behaviour, which crosses the criminal and social policy fields with a wide skillset to match. A number of factors including national policy, community expectations, and multi-partnership engagement influence their dynamic working culture.

Evaluating early administration of the hydroxymethylglutaryl-CoA reductase inhibitor simvastatin in the prevention and treatment of delirium in critically ill ventilated patients (MoDUS trial): Study protocol for a randomized controlled trial

Background: The incidence of delirium in ventilated patients is estimated at up to 82%, and it is associated with longer intensive care and hospital stays, and long-term cognitive impairment and mortality. The pathophysiology of delirium has been linked with inflammation and neuronal apoptosis. Simvastatin has pleiotropic properties; it penetrates the brain and, as well as reducing cholesterol, reduces inflammation when used at clinically relevant doses over the short term. This is a single centre randomised, controlled trial which aims to test the hypothesis that treatment with simvastatin will modify delirium incidence and outcomes. 

Methods/Design: The ongoing study will include 142 adults admitted to the Watford General Hospital Intensive Care Unit who require mechanical ventilation in the first 72 hours of admission. The primary outcome is the number of delirium- and coma-free days in the first 14 days. Secondary outcomes include incidence of delirium, delirium- and coma-free days in the first 28 days, days in delirium and in coma at 14 and 28 days, number of ventilator-free days at 28 days, length of critical care and hospital stay, mortality, cognitive decline and healthcare resource use. Informed consent will be taken from patient's consultee before randomisation to receive either simvastatin (80 mg) or placebo once daily. Daily data will be recorded until day 28 after randomisation or until discharge from the ICU if sooner. Surviving patients will be followed up on at six months from discharge. Plasma and urine samples will be taken to investigate the biological effect of simvastatin on systemic markers of inflammation, as related to the number of delirium- and coma-free days, and the potential of cholinesterase activity and beta-amyloid as predictors of the risk of delirium and long-term cognitive impairment. 

Discussion: This trial will test the efficacy of simvastatin on reducing delirium in the critically ill. If patients receiving the statin show a reduced number of days in delirium compared with the placebo group, the inflammatory theory implicated in the pathogenesis of delirium will be strengthened. 

Surviving the industrial city: the female poor and the workhouse in late nineteenth-century Belfast

In common with many British cities, but unlike the rest of Ireland, late nineteenth-century Belfast experienced rapid industrialization and physical expansion. Women formed a significant proportion of the city’s workforce, attracted by the employment opportunities represented in the burgeoning textile industry. Many of them were economically vulnerable, however, and could find themselves destitute for a number of reasons. This article sets Belfast’s Poor Law workhouse in the landscape of welfare in the city, exploring how its use reflected the development of the city and the ways in which the female poor engaged with it in order to survive.