The Binding Characteristics and Number of β-Adrenergic Receptors on the Turkey Erythrocyte

Turkey erythrocyte ghosts (empty membranes) possess a class of receptors that can bind both L-[(3)H]isoproterenol and DL-[(3)H]propranolol. The binding of [(3)H]isoproterenol to these receptors occurs with a dissociation constant of 0.15 muM and can be fully inhibited by 1 muM propranolol. The binding of [(3)H]propranolol occurs with a dissociation constant of 2.5 nM and can be fully inhibited by 0.2 mM DL-isoproterenol. Ligand binding is sensitive to sonication, boiling, and 8 M urea. The cells possess 500 to 1000 beta-adrenergic receptors per cell. Binding of propranolol to the beta-receptor was found to be stereospecific for the L stereoisomer. If one assumed a 1:1 relationship between beta-adrenergic receptors and adenylate cyclase, the turnover number of this adenylate cyclase would be close to 100 min(-1).     

Access to the next wave of biologic therapies (Abatacept and Tocilizumab) for the treatment of rheumatoid arthritis in England and Wales

Patients in England and Wales with rheumatoid arthritis (RA) receive treatment from the National Health Service (NHS) with therapies approved by the European Medicines Agency (EMA), under guidance from the National Institute for Health and Clinical Excellence (NICE). This document overviews the current NICE guidelines for the treatment of RA and identifies scenarios when such guidance may not represent the optimum management strategy for individual patients. Specifically, we consider the use of tocilizumab or abatacept as the most appropriate treatments for some patients. In such scenarios, it may be possible for the clinician to secure access to the required therapy through an application procedure known as an 'individual funding request', the process of which is described in detail here. At present, it is unclear the extent to which the proposed reform of the NHS will affect the role of NICE in providing guidance and setting standards of care. Until the full impact of the proposed changes are realized, individual funding requests will remain a valuable way of securing the optimal treatment for all patients suffering from RA.     

An experimental study exploring the relationship between the size of bacterial inoculum and bacterial adherence to prosthetic mesh

Background

Infection is a major concern with medical implants. Surgical meshes used for the repair of abdominal wall hernias are associated with wound infection rates ranging from 7 to 18 %. Although mesh infection is relatively rare, once a patient shows clinical signs of mesh infection, the surgeon may be required to remove the mesh, resulting in additional surgery, morbidity, and cost. The usual causative organisms associated with cases of mesh infection are Staphylococcus species. The first stage of implant infection is bacterial adherence to the biomaterial. An accurate assessment of adherent bacteria to medical prosthetics is therefore important in order to determine the infection risk associated with surgical implants.

Methods

This experimental study evaluated the relationship between the size of the bacterial inoculum and bacterial adherence to three commonly used hernia prosthetics (polypropylene, polyester, and ePTFE). Tenfold dilutions of S. epidermidis (Evans-ATCC 12228) and S. aureus (Rosenbach-ATCC 25923), created with phosphate-buffered saline, were used to inoculate each of the meshes in 3 ml of tryptone soya broth for 18 h at 37 °C, 95 % air/5 % CO₂. The number of viable bacteria in each dilution was calculated using a spot plate technique. The number of adherent bacteria to the meshes was counted using direct imaging analysis with scanning electron microscopy and expressed as a mean.

Results

One hundred eight mesh samples were analysed. The size of the bacterial inoculum of S. epidermidis significantly influenced the number of adherent bacteria to the mesh, and lower rates of adhesion were observed with smaller inoculums for all three meshes (polypropylene, p = 0.02; ePTFE p = 0.03; polyester p = 0.02). A similar, albeit less profound, pattern of results was observed with S. aureus. Bacterial adherence was observed with inoculum sizes as small as <10 bacteria.

Conclusions

The results demonstrate that even a very low number of bacterial inoculums can result in adherence to hernia biomaterials and that the level of adherence is directly related to the size of the inoculum. These in vitro results provide evidence that the size of the inoculum is important in the colonization of hernia biomaterials and demonstrate the importance of minimising the bacterial inoculum in the clinical setting.     

Prevalence and risk factors for reduced sound tolerance (hyperacusis) in children

Objective: To estimate the prevalence of reduced sound tolerance (hyperacusis) in a UK population of 11-year-old children and examine the association of early life and auditory risk factors with report of hyperacusis. Design: A prospective UK population-based study. Study sample: A total of 7097 eleven-year-old children within the Avon longitudinal study of parents and children (ALSPAC) were asked about sound tolerance; hearing and middle-ear function was measured using audiometry, otoacoustic emissions, and tympanometry. Information on neonatal risk factors and socioeconomic factors were obtained through parental questionnaires. Results: 3.7% (95% CI 3.25, 4.14) children reported hyperacusis. Hyperacusis report was less likely in females (adj OR 0.64, 95% CI 0.49, 0.85), and was more likely with higher maternal education level (adj OR 1.72, 95% CI 1.08, 2.72) and with readmission to hospital in first four weeks (adj OR 1.98, 95% CI 1.20, 3.25). Report of hyperacusis was associated with larger amplitude otoacoustic emissions but with no other auditory factors. Conclusions: The prevalence of hyperacusis in the population of 11-year-old UK children is estimated to be 3.7%. It is more common in boys.     

Identification of a Campylobacter jejuni protein that cross-reacts with cholera toxin

The question of whether Campylobacter jejuni produces a cholera toxin-like toxin (CTLT) has been controversial. The objective of this study was to identify the factor that cross-reacts with CT from C. jejuni. Filtrates of C. jejuni grown in four different liquid media reported to promote CTLT production were tested by Chinese hamster ovary (CHO) cell elongation assay and for reactivity with CT antibody using GM1 ganglioside enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Protein sequence was determined by matrix-assisted laser desorption ionization-time of flight (MALDI TOF-TOF). Filtrates from seven reference strains reported to produce CTLT and from 80 clinical strains were negative in the CHO cell assay, but those from three reference strains and 16 clinical strains were positive by GM1 ELISA. All strains tested, including C. jejuni NCTC 11168, which does not contain a CT gene homologue, possessed a 53-kDa protein which reacted with CT antibody by immunoblotting. This band was identified as the major outer membrane protein, PorA, of C. jejuni. CT antibody reacted by immunoblotting with a recombinant PorA, but antibody to the recombinant PorA did not react with CT. Our results indicate that C. jejuni does not produce a functional CTLT, but the reactivity of PorA with CT antibody would lead to the erroneous conclusion that C. jejuni produces a functional CTLT.     

Correlates of self-reported and clinically assessed depression in male heroin addicts

Used the Raskin Depression Scale, Hamilton Psychiatric Rating Scale for Depression, Beck Depression Inventory, and the Profile of Mood States' Depression-dejection scale to measure depression in 152 male heroin addicts who were seeking methadone maintenance. To derive an estimate of depression that combined the former two instruments' clinical ratings and the latter two measures' self-reports, a principal component analysis was performed on the intercorrelations among the four scales. One significant component emerged, and its component scores then were correlated with some of the addicts' background characteristics. Living with another addict, being unemployed, and having previously attempted drug abuse treatment were related positively to the combined estimate of depression. The four scales' mean scoras also indicated that the sample was mildly depressed.