Sensitivity to cinnamic aldehyde in a toothpaste. 2. Further studies

The authors carried out further studies to assess the significance of the findings of patients sensitive to cinnamic aldehyde in a toothpaste. Selected groups of patients in whom sensitivity to this might have been overlooked were patch-tested. With the exception of three patients, two with cosmetic sensitivity and one with hand eczema, the results were negative. The frequency of use of the original toothpaste was assessed among patients attending the clinic and this was followed by a circular letter to general practitioners and dentists inviting referral of patients with oral symptoms. As a result, five further cases, four of whom gave positive patch test reactions to cinnamic aldehyde, were discovered. The authors emphasize the importance of attempting to obtain accurate information as quickly as possible when 'new' or hitherto unsuspected allergens are implicated.     

An evaluation of the intravenous vitamin D test in geriatric patients with suspected osteomalacia.

In 30 elderly patients, the measurement of serum phosphate levels before and after intravenous vitamin D3 was not found to be a useful way of predicting the presence or absence of osteomalacia as determined by bone biopsy.     

Role of ectodomain lysines in the subunits of the heteromeric P2X2/3 receptor

Lysine residues near each end of the receptor ectodomain (in rat P2X2 Lys69 and Lys308) have been implicated in ATP binding to P2X receptors. We recorded membrane currents from human embryonic kidney cells expressing P2X subunits and found that lysine-to-alanine substitutions at equivalent positions in the P2X3 receptor (Lys63 and Lys299) also prevented channel function. Heteromeric P2X2/3 receptors are formed when P2X2 and P2X3 subunits are expressed together; they can be distinguished by their relatively sustained response to alphabeta-methylene-ATP. By coexpression of wild-type P2X3 and mutated P2X2 subunit, we found that the heteromeric P2X2/3 channel functioned normally when either lysine in the P2X2 subunit was mutated to alanine (i.e., [K69A] or [K308A]) but not when both lysines were mutated to alanine (i.e., [K69A, K308A]). However, coexpression of wild-type P2X2 with a mutated P2X3 subunit ([K68A] or [K299A]) produced no functional heteromers. The rescue of the single lysine mutant P2X2 subunit by wild-type P2X3 (but not the converse) suggests that the heteromeric channel contains one P2X2 and two P2X3 subunits and that the receptor functions essentially normally as long as two subunits are not mutated. The failure to rescue function in the P2X2 subunit with both lysines mutated by wild-type P2X3 suggests that these residues from two different subunits interact in agonist binding or channel opening.     

Characterization of nicotine's ability to serve as a negative feature in a Pavlovian appetitive conditioning task in rats

Rationale Pavlovian feature negative discriminations have been widely used to understand inhibitory conditioning processes using exteroceptive stimuli. Comparatively little is known about inhibitory conditioning processes using a drug state as a negative feature. A negative feature signals that presentation of a conditional stimulus (CS) will not be paired with an unconditioned stimulus. Objectives The present research examined whether nicotine served as a negative feature and started characterizing its properties. Methods and results In acquisition, rats received intermixed saline and nicotine (0.4 mg/kg, base) sessions. On saline sessions, a 15-s light CS was paired with 4-s access to sucrose; the CS was presented on nicotine sessions, but sucrose was withheld. The discrimination was acquired with more goal tracking during the CS on saline sessions. Nicotine's inhibition of this conditioned response (CR) was sensitive to nicotine dose (ED₅₀=0.225) and injection to testing interval (CR returned at 200 min). Mecamylamine pretreatment, but not hexamethonium, produced a loss of inhibitory control by nicotine suggesting a role for central nicotinic acetylcholine receptors. Amphetamine, bupropion, arecoline, and chlordiazepoxide, but not caffeine, substituted for the nicotine feature. However, in locomotor tests, amphetamine and bupropion increased activity; arecoline and chlordiazepoxide decreased activity. For this reason, the motor effects of these ligands could not be dissociated from substitution via shared stimulus properties. Conclusions This feature negative task provides a preclinical model for studying how drug states inhibit responding, although identifying the process(es) mediating CR inhibition will require further research.     

Mucosal transmission of HIV-1: first stop dendritic cells

Worldwide the heterosexual route is the prevalent mode of transmission of HIV, increasing the demand for measures that block the sexual spread of HIV infection. Vaccines designed to prevent mucosal transmission of HIV should be considered a component of vaccine strategies against HIV (in addition to cytotoxic T cells required for clearance and to prevent viral dissemination) and include antibodies, which are capable of blocking HIV entry at mucosal epithelial barriers, and prevent initial infection of target cells in the mucosa. However, in the interim and in the absence of an effective vaccine, the development of microbicides, topical preparations that block the early steps of HIV infection and transmission, may represent a more viable alternative to condom use in many HIV infected regions of the world especially by empowering women. To date there has been some success with antiviral antibodies applied as a microbicide capable of preventing SIV infection in macaques and reports of vaccines capable of preventing intravaginal and intrarectal inoculated SIV. However, for such success in humans a much greater understanding of the mechanisms involved in the very early stages of mucosal transmission in HIV infection are required. These may lead to additional strategies to inactivate or inhibit viral uptake and replication before a potentially life threatening acute infection develops. Such measures will lead to the development of effective microbicides and vaccines that will diminish the global spread of HIV.     

Lanolin of reduced sensitizing potential

Confirmation has been obtained that reducing the content of natural free alcohols in lanolin to below 3 % particularly in the absence of detergent residues, reduces the incidence of positive patch test reactions amongst selected lanolin-sensitive skin patients by 99.3 %. Only one reaction out of 149 subjects was recorded.     

111-Indium labelled canine platelets.

This paper describes a method of separating and labelling canine platelets with lll-In-oxine with full retention of aggregation responses to adenosine diphosphate. The technique required only 22.5 ml of blood and the labelled platelets were reinjected within 45 minutes of initial venepuncture. The platelet survival in beagle dogs was shown to be linear with 13.6% loss per day from the intravascular space, giving a total survival time of 7 days. The mean labelling efficiency was 85% and elution of the isotope from the platelets was reproducibly less than 2%.