Analysis of pre- and postsynaptic activity in the frog semicircular canal following ototoxic insult: differential recovery of background and evoked afferent activity

Frogs were treated with a single dose of gentamicin administered intraotically to produce severe degeneration of posterior semicircular canal hair cells and to evaluate the time course of functional damage and recovery both at pre- and postsynaptic level. In isolated canal preparations the endoampullar potential, which reflects the summed receptor potentials of crista hair cells, was progressively reduced in amplitude and completely abolished 6 days after gentamicin treatment. At this time the crista epithelium was devoid of hair cells. The recovery of the endoampullar potential began around 9 days after the ototoxic insult and its amplitude progressively increased to reach, after 20 days, values close to those observed in control experiments. The endoampullar potential amplitude was related to the degree of hair cell regeneration in the crista epithelium. Consistent with the presynaptic damage, the slow generator potential (representing the summed miniature excitatory postsynaptic potential [mEPSP] activity of all posterior nerve fibres) and the resting and evoked spike discharge recorded from the whole ampullar nerve were abolished 6 days after gentamicin treatment. The recovery of the background and evoked afferent activity showed different behaviours. Background spike activity became detectable around 8 days after the ototoxic insult, but was not modulated by canal stimulation at this time, and no generator potential was detected. Moreover, the resting spike frequency fully recovered and reached control values around 15 days after gentamicin treatment, whereas the evoked activity attained normal values only 20 days after the ototoxic insult. These results were confirmed by intracellular recordings from single afferent fibres of the ampullar nerve in intact labyrinth preparations. Absence of any resting and evoked discharge was the most common pattern observed in the early period from 7 to 8 days after gentamicin treatment. Fifty-five percent of impaled afferents were silent while the others showed low resting frequencies of mEPSPs and spikes, and were unresponsive to canal rotation. In the intermediate period from 14 to 15 days after gentamicin treatment, background mEPSP and spike frequencies approached those evaluated in control experiments, but the frequencies of the evoked mEPSPs and spikes were clearly lower than in controls. In the late period, from 18 to 20 days after the ototoxic insult, the impaled afferents showed normal evoked mEPSP and spike frequencies. The present data indicate that the frog semicircular canal completely recovers its pre- and postsynaptic activity following severe ototoxic insult. During the regeneration process, the cytoneural junction regains function and the resting discharge reappears before recovery of mechanoelectrical transduction

National Italian Guidelines for caries prevention in 0 to 12 years-old children

AIM: Oral and dental health improved tremendously over the last fifty years in Italy but still prevalence of dental caries in children remains a significant clinical problem. This report describes the National Italian Guidelines for caries prevention. METHODOLOGY: A panel of experts coordinated by the Italian Society of Paediatric Dentistry (SIOI) planned to elaborate the national Italian guidelines for caries prevention in children. The structure of the guidelines has been planned to follow the principles of modern caries treatment and management as well as science based dentistry. The main procedure was based on a hierarchic evaluation of literature. CONCLUSION: The guidelines are planned for dentist working in primary dental care, however, they are also designed to be of interest for other care professionals such as paediatricians, gynecologists, pharmacists and general medical practitioners and also for parents and/or guardians of the children

PERTINENT - PERindopril-Thrombosis, InflammatioN, endothelial dysfunction and neurohormonal activation trial: A sub-study of the EUROPA study

BACKGROUND: Markers of thrombosis, inflammation, endothelial dysfunction and neurohumoral activation such as fibrinogen, D-dimer, C-reactive protein, von Willebrand factor, tumour necrosis factor-alpha and chromogranin-A are reported to be linked to the increase of cardiovascular risk for atherosclerosis progression and events in patients with cardiovascular diseases. METHODS: EUROPA is a double blind, placebo-controlled trial on 12,231 patients that evaluates the effect of an angiotensin converting enzyme inhibitor--perindopril--on prevention of cardiovascular events in patients with coronary artery disease. PERTINENT is a sub-study of EUROPA that evaluates (a) in Part A (300 patients): the influence of perindopril vs. placebo on fibrinogen, D-dimer, C-reactive protein, von Willebrand factor, tumour necrosis factor-alpha and chromogranin-A. In addition, NOS expression and induction of apoptosis on human umbilical vein endothelial cells and angiotensin converting enzyme levels are also studied; (b) in Part B (about 1200 patients): the predictive role of plasma levels of C-reactive protein and von Willebrand factor on the occurrence of cardiovascular events. To this end, matched case-control analyses are planned (patients with vs. patients without events). STATUS OF PERTINENT: Blood analyses are in progress in four specialised laboratories: (a) Gaubius Laboratory, Leiden, TNO-PG, The Netherlands; (b) University Department of Medicine, Birmingham, UK; (c) University of Pavia, Italy; (d) Fondazione Salvatore Maugeri, Cardiovascular Research Centre, Gussago, Italy. CONCLUSIONS: The PERTINENT sub-study might help elucidating the phenomena contributing to the pathophysiology of cardiovascular events in patients with coronary artery disease and the role of perindopril in such context

Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study)

BACKGROUND: Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces the rate of cardiovascular events among patients with left-ventricular dysfunction and those at high risk of such events. We assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure. METHODS: We recruited patients from October, 1997, to June, 2000. 13655 patients were registered with previous myocardial infarction (64%), angiographic evidence of coronary artery disease (61%), coronary revascularisation (55%), or a positive stress test only (5%). After a run-in period of 4 weeks, in which all patients received perindopril, 12218 patients were randomly assigned perindopril 8 mg once daily (n=6110), or matching placebo (n=6108). The mean follow-up was 4.2 years, and the primary endpoint was cardiovascular death, myocardial infarction, or cardiac arrest. Analysis was by intention to treat. FINDINGS: Mean age of patients was 60 years (SD 9), 85% were male, 92% were taking platelet inhibitors, 62% beta blockers, and 58% lipid-lowering therapy. 603 (10%) placebo and 488 (8%) perindopril patients experienced the primary endpoint, which yields a 20% relative risk reduction (95% CI 9-29, p=0.0003) with perindopril. These benefits were consistent in all predefined subgroups and secondary endpoints. Perindopril was well tolerated. INTERPRETATION: Among patients with stable coronary heart disease without apparent heart failure, perindopril can significantly improve outcome. About 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event. Treatment with perindopril, on top of other preventive medications, should be considered in all patients with coronary heart disease