Weakened anterior roots--intraradicular rehabilitation.

This paper highlights the fact that many anterior teeth requiring restoration are severely weakened having wide, flared canal spaces, and thin dentinal walls that are prone to fracture. Traditionally these teeth have been restored using metal posts and are often unsuccessful because of lack of retention or root fracture. This paper describes how mineral trioxide aggregate (MTA) can be used to form an immediate apical seal rather than waiting months for apexification. Weakened roots can be reinforced using dentine bonding agents and composite resin and if insufficient coronal tooth structure is present a quartz-fibre post can be placed to retain a composite core.

Post and core systems, refinements to tooth preparation and cementation.

With a plethora of post systems available, it is often difficult to decide which one to use. This is made more difficult by the fact that new posts are introduced before existing ones are fully evaluated in laboratory and clinical studies. This paper therefore describes the different post types and the main advantages and disadvantages of each. In addition, the choice of post system will influence whether further tooth preparation is required and will dictate which luting cement and core material are most appropriate. Whilst the choice of post will, for many dentists, be driven by personal preference and a history of clinical success, there are certain pit falls to avoid and these are outlined.

Restoration of the root-filled tooth: pre-operative assessment.

This is the first in a series of four papers related to the management of root canal treated teeth. When teeth compromised by extensive restorations become non-vital, suggestions have been given as to how root canal treatment can be carried out with the greatest chance of success. Once root canal treated, either by a previous dentist or by the current dentist, a review of the assessment process that should be carried out prior to placing costly indirect definitive restorations is given. It will be clear that post-retained restorations are mainly reserved for anterior or single-rooted teeth, posterior teeth rarely requiring a post for core retention. The second paper in this series describes the basic tooth preparation that should be carried out prior to placing a post. Depending on the type of post system used, further modifications to tooth preparation may be required and the cementation techniques may also have to be modified. The third paper therefore discusses the various post types, when and how they should be used for optimum results. The final paper addresses reinforcement and restoration of compromised root canals, such as those with immature, open apices, or those that have been over-prepared for previous post-retained restorations.

Tooth preparation for post-retained restorations.

Failure of root canal treatment and/or post crowns can be avoided in many cases if appropriate tooth preparation is carried out. This paper discusses the rationale for the timing of post placement following root canal treatment and appropriate methods for removal of gutta-percha prior to post space preparation. The basic principles of post space preparation are described, which should reduce the risk of weakening the root unnecessarily, causing damage to the periodontium and post perforation.

Therapeutic advantages of third generation antihistamines.

A third generation of antihistamines is emerging for the treatment of allergic rhinitis and chronic urticaria. First generation antihistamines are among the most widely used drugs in the world, and provide symptomatic relief from allergies and the common cold to millions of patients, mainly in OTC combination preparations. Their full potential is limited by the sedation caused by their effects on histamine receptors in the brain. Second generation antihistamines (terfenadine, astemizole, loratadine and cetirizine), which block peripheral H1 receptors without penetrating the blood-brain barrier, were developed and introduced from 1981 onwards to provide comparable therapeutic benefit without the CNS side-effects. Although largely successful in this goal, terfenadine and astemizole were found to cause potentially serious arrhythmias when plasma concentrations became elevated subsequent to impaired metabolism. It was established that the cardiac toxicity was mainly due to the parent drugs. As active metabolites could account for most of the clinical benefit, the goal for the third generation of antihistamines became to develop therapeutically active metabolites that were devoid of cardiac toxicity. The first of these drugs, fexofenadine (the active metabolite of terfenadine), was approved in July 1996, after an unusually rapid development programme. Its introduction set a new standard of safety that led the FDA to request the withdrawal of terfenadine in 1997 on the grounds that a safer version of an equivalent drug was now available. Norastemizole and descarboethoxy loratadine, the metabolites of astemizole and loratadine, respectively, are also in clinical development. These offer comparable or superior clinical benefits.

Oxidant injury, nitric oxide and pulmonary vascular function: implications for the exercising horse.

The athletic ability of the horse is facilitated by vital physiological adaptations to high-intensity exercise, including a thin (but strong) pulmonary blood-gas barrier, a large pulmonary functional reserve capacity and a consequent maximum oxygen uptake (VO2max) far higher than in other species. A high pulmonary artery pressure also serves to enhance pulmonary function, although stress failure of lung capillaries at high pulmonary transmural pressures, and the contribution of other factors which act in the exercising horse to increase pulmonary vascular tone, may lead to pathological or pathophysiological sequelae, such as exercise-induced pulmonary haemorrhage (EIPH). Reactive oxygen species (ROS) are an important component of the mammalian inflammatory response. They are released during tissue injury and form a necessary component of cellular defences against pathogens and disease processes. The effects of ROS are normally limited or neutralized by a multifactorial system of antioxidant defences, although excessive production and/or deficient antioxidant defences may expose healthy tissue to oxidant damage. In the lung, ROS can damage pulmonary structures both directly and by initiating the release of other inflammatory mediators, including proteases and eicosanoids. Vascular endothelial cells are particularly susceptible to ROS-induced oxidant injury in the lung, and both the destruction of the pulmonary blood-gas barrier and the action of vasoactive substances will increase pulmonary vascular resistance. Moreover, ROS can degrade endothelium-derived nitric oxide (NO), a major pulmonary vasodilator, thereby, with exercise, synergistically increasing the likelihood of stress failure of pulmonary capillaries, a contributing factor to EIPH. This review considers the implications for the exercising horse of oxidant injury, pulmonary vascular function and NO and the contribution of these factors to the pathogenesis of equine respiratory diseases.

First recorded outbreak of equine viral arteritis in the United Kingdom.

Equine viral arteritis was diagnosed for the first time in the United Kingdom in 1993. The outbreak began on a non-thoroughbred stud in south Nottinghamshire and spread to five other premises through chilled semen used for artificial insemination and from acutely and subclinically infected mares returning home. The outbreak was contained on these six premises by means of voluntary movement restrictions. The most commonly observed clinical signs were typical: pyrexia with depression, and conjunctivitis with periorbital oedema; nasal discharge, and oedema of the distal limbs, prepuce and mammary glands were less common. The first mare to be covered by a recently imported stallion was the first animal to be affected. The mare was resident and no new mares had arrived on the stud during the previous five months. About 100 animals became infected during the outbreak, including three indigenous stallions. Equine arteritis virus was isolated from semen and heparinised blood samples and seroconversions were demonstrated by using the equine arteritis virus neutralisation test. Although the outbreak was contained, the free movement of animals within the European Union increases the possibility of infected stallions being introduced into the UK.

Inhibition of long-chain acylcarnitine accumulation during coronary artery occlusion does not alter infarct size in dogs.

We tested whether inhibition of carnitine acyl-transferase-1 (CAT-1) during coronary artery occlusion can limit infarct size (IS) by suppressing accumulation of long-chain acylcarnitines (LCAs), potentially cytotoxic intermediates of fatty acid metabolism. The CAT-1 inhibitor 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) was administered to dogs before 90-min occlusion and 4-h reperfusion of the left anterior descending or left circumflex coronary artery (LAD, LCX). Dogs in the LAD occlusion series received 7.5 (n = 5) or 15 (n = 2) mg/kg POCA intravenously (i.v.); dogs in the LCX occlusion series received 15 mg/kg i.v. (n = 7); an equal number were treated with drug vehicle. Biopsies were obtained for determination of myocardial LCAs. The region at risk and IS were delineated by dye injection and tetrazolium staining. In vehicle-treated dogs, myocardial LCAs (in picomoles per milligram of wet weight +/- SEM) increased from 11 +/- 3 to a peak of 75 +/- 24 during LAD occlusion and from 32 +/- 10 to 192 +/- 55 during LCX occlusion. In POCA-treated dogs LCAs increased from 12 +/- 2 to only 33 +/- 13 pmol/mg wet weight during LAD occlusion (p < 0.05 vs. vehicle) and did not increase significantly during LCX occlusion; 22 +/- 8 to 27 +/- 5 pmol/mg wet weight (p < 0.005 vs. vehicle). LCX occlusion resulted in larger areas at risk and larger infarcts (as a percentage of left ventricle) than did LAD occlusion. IS as a percentage of the region at risk did not differ significantly among the experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Reperfusion-induced accumulation of long-chain acylcarnitines in previously ischemic myocardium.

Long-chain acylcarnitines (LCA) have been shown to accumulate during myocardial ischemia and to contribute to malignant derangements characteristic of ischemia. We detail the time course of the increase in LCA levels during both ischemia and reperfusion. Evidence indicates an additional specific reperfusion-induced increase in LCA that peaks at 2 min and decreases to basal levels by 30 min. This increase in LCA during reperfusion is observed after 2-, 10-, or 20-min ischemia and is inhibited by the presence of the carnitine palmitoyl transferase 1 (CPT1) inhibitor phenyloxirane carboxylic acid (POCA). A role for increased LCA in mediating "reperfusion damage" is not indicated, however, because POCA did not attenuate either the incidence of ventricular fibrillation (VF) during early reperfusion or the survival rate of rats undergoing 24-h reperfusion after 10-min occlusion.

Electropharmacology of dofetilide, a new class III agent, in anaesthetised dogs.

In open chest anaesthetised dogs, dofetilide increased the ventricular effective refractory period over the dose range 1-100 micrograms/kg i.v. and the ventricular fibrillation threshold at doses between 3-100 micrograms/kg and was 80-1000 times more potent than sematilide, racemic sotalol, d-sotalol or quinidine. The maximal increases in ventricular fibrillation threshold induced by sematilide and quinidine were less than that induced by the other drugs. A change in the character of the induced arrhythmia from true ventricular fibrillation to a rapid ventricular flutter, with frequent spontaneous conversion, was observed following all drugs. No adverse haemodynamic effects of dofetilide, sematilide or d-sotalol were observed, but quinidine induced marked cardiac depression and racemic sotalol also impaired left ventricular contractility. All drugs reduced heart rate, though the effect of racemic sotalol was clearly greater than that of the other agents. Dofetilide is a potent class III antiarrhythmic agent with antifibrillatory properties and a favourable haemodynamic profile.

Effects of action potential prolongation via different cellular mechanisms on the electrophysiological properties of rat and guinea-pig ventricular myocardium.

The effects of d-sotalol and the sea anemone toxin ATXII on the electrophysiological properties of rat and guinea-pig ventricular myocardium in vitro and on arrhythmias following coronary artery ligation in rat hearts in vivo were studied. ATXII (1-5 nM) prolonged the cardiac action potential of isolated papillary muscles and the effective refractory period of perfused hearts from both rats and guinea-pigs. In rat hearts, ATXII induced gross action potential prolongation and early afterdepolarizations at concentrations above 1 nM. In contrast, d-sotalol prolonged the action potential and effective refractory period of guinea-pig, but not of rat myocardium. Neither drug prevented arrhythmias in anaesthetized rats following coronary ligation.