Knowledge of Australian primary education providers towards dental avulsion injuries: a cross-sectional study.

BACKGROUND/AIM: The aim of this study was to evaluate the knowledge of school professionals regarding the emergency management of dental avulsion. METHODS: This cross-sectional study utilised a self-administered, pilot-tested questionnaire for school staff from primary schools. Descriptive statistics were used for the analysis - the prevalence and univariate associations between a categorical outcome and the variables under consideration, were evaluated using Pearson's Chi-squared test. RESULTS: This survey yielded a response rate of 43.5% (n = 313). Approximately 60% of participants held valid first-aid certificates and 23% had received avulsion advice previously. Over 80% of participants expressed an unwillingness to replant an avulsed tooth, and over 90% believed that there should be greater awareness in this area. This unwillingness to replant was influenced by respondents' age (x2 = 8.13 df = 3, P = 0.043) and receiving advice previously (x2 = 13.15, df = 1, P < 0.001). Under-preparedness was related to years of experience (x2 = 15.03, df = 5, P = 0.010), first-aid training (x2 = 6.41, df = 1, P = 0.011) and receiving advice previously (x2 = 43.47, df = 1, P < 0.001). It was also evident that first-aid training positively influenced appropriate dental referral in the management pathway (x2 = 10.49, df = 1, P = 0.001). CONCLUSION: This study suggests that there is an inadequate level of knowledge on the appropriate management of dental avulsion injuries amongst primary school professionals in Australia.

Neurogenic inflammation is associated with development of edema and functional deficits following traumatic brain injury in rats.

The present study has used capsaicin-induced neuropeptide depletion to examine the role of neurogenic inflammation in the development of edema and functional deficits following traumatic brain injury (TBI). Adult, male rats were treated with capsaicin (neuropeptide-depleted) or equal volume vehicle (controls) 14 days prior to induction of moderate/severe diffuse TBI. Injury in vehicle treated control animals resulted in acute (4-5 h) edema formation, which was confirmed as being vasogenic in origin by diffusion weighted magnetic resonance imaging and the presence of increased permeability of the blood-brain barrier (BBB) to Evans blue dye. There was also a significant decline in brain magnesium concentration, as assessed by phosphorus magnetic resonance spectroscopy, and the development of profound motor and cognitive deficits. In contrast, capsaicin pre-treatment resulted in a significant reduction in post-traumatic edema formation (p < 0.001), BBB permeability (p < 0.001), free magnesium decline (p < 0.01) and both motor and cognitive deficits (p < 0.001). We conclude that neurogenic inflammation may play an integral role in the development of edema and functional deficits following TBI, and that neuropeptides may be a novel target for development of interventional pharmacological strategies.

Neuropeptide release influences brain edema formation after diffuse traumatic brain injury.

The mechanisms associated with edema formation after traumatic brain injury (TBI) have not been fully elucidated. In peripheral tissue injury, the neurogenic component of inflammation plays a significant role in increased vascular permeability and edema formation. However, few studies have examined the role of neuropeptide induced neurogenic inflammation following TBI. Adult male Sprague-Dawley rats were either left untreated, or pre-treated with capsaicin (125 mg/kg s.c.) or equal volume vehicle, and injured 14 days later using the 2-meter impact-acceleration model. Subgroups of animals were assessed for blood brain barrier (BBB) permeability (Evans Blue), brain edema (wet weight/dry weight) and functional outcome (Barnes maze and Rotarod) for up to 2 weeks post-trauma. Increased BBB permeability was present in untreated animals between 3 and 6 h after injury but not at later time-points. Edema was maximal at 5 h after trauma, declined and then significantly increased over the 5 days post-trauma. In contrast, capsaicin pre-treated, neuropeptide-depleted animals exhibited no significant increase in BBB permeability or edema compared to vehicle treated animals after injury. Notably, motor and cognitive impairments were significantly reduced in the capsaicin-pretreated animals. We conclude that neurogenic inflammation contributes to the development of edema and posttraumatic deficits after diffuse TBI.

Circular versus longitudinal myometrial contractile response to selective tachykinin receptor agonists in rat.

This study compared the nature and magnitude of the contractile response produced in vitro by selective NK1, NK2 and NK3 tachykinin receptor agonists in circularly and longitudinally oriented strips of myometrium from ovariectomised and ovariectomised oestrogen-treated rats. The nature of the responses produced upon stimulation of the tachykinin receptors varied between the different myometrial preparations and the hormonal environment from which the tissue was taken. Variations included: (i) sustained contraction until washout of agonist; (ii) biphasic contraction until washout of agonist; and (iii) monophasic contraction. The major differences in magnitude of contractions were seen in preparations from oestrogen-treated animals in which responses to stimulation of all tachykinin receptors were reduced in comparison to preparations from non-oestrogen treated animals. Furthermore, the responses in circularly oriented myometrium preparations from oestrogen-treated animals were all markedly reduced compared to responses in longitudinally oriented myometrium preparations. These results suggest that the tachykinin receptors in longitudinally and circularly oriented myometrial layers are differentially regulated, especially in tissue isolated from an oestrogen-dominated environment.

An overview of new and novel pharmacotherapies for use in traumatic brain injury.

1. Although a number of interventional pharmacotherapies have undergone clinical trial in traumatic brain injury (TBI), none has shown considerable promise. The present short review will examine some of the more novel compounds that have been proposed recently as potential therapeutic agents for use in TBI. 2. Previous experimental studies have demonstrated that brain intracellular free magnesium significantly declines following TBI and that the administration of magnesium salts attenuates the post-traumatic neurological deficits. More recent studies have established that magnesium salts administered after trauma enter the brain intracellular space and reduce the size of the lesion volume. Such protection could be afforded through attenuation of both necrotic and apoptotic cell death. Magnesium salts are currently on clinical trial in TBI. 3. Cyclosporine A is known to inhibit opening of the mitochondrial permeability transition pore. Administration of cyclosporine A after TBI has been shown to attenuate axonal injury and decrease the resultant lesion volume. Therefore, inhibitors of mitochondrial transition pore opening and resultant attenuation of apoptosis show some promise as neuroprotective agents. 4. Recent evidence has shown that substance P antagonists may decrease lesion volume and improve neurological outcome after ischaemia. Similar findings have recently been reported in TBI. The fact that substance P antagonists are known to reduce neurogenic inflammation, oedema formation and are clinically being trialed as both antidepressants and antinociceptive agents suggests that these agents warrant further investigation as therapeutic agents following TBI. 5. There are numerous contradictions in the literature regarding the potential neuroprotective effects of the hormones oestrogen and progesterone. Recent studies suggest that both hormones are protective in TBI and further studies are required to ascertain the mechanisms associated with this protection and any potential for clinical application.

Hormonal variation of rat uterine contractile responsiveness to selective neurokinin receptor agonists.

Regulated uterine contractions are important in many reproductive functions such as sperm transport and embryo positioning during implantation. The role of classical neurotransmitters including acetylcholine and norepinephrine in regulating myometrial contractility has been well studied; however, the peripheral role of sensory neurotransmitters such as the neurokinins is less clear. The major neurokinins are substance P, neurokinin A, and neurokinin B, which predominantly activate neurokinin receptors (NK-Rs) 1, 2, and 3, respectively. This study utilized selective receptor agonists to examine the role of NK-Rs in uterine contractility. Uterine tissues, obtained from the major stages of the rat estrous cycle, were stimulated with selective NK-R agonists. Addition of each agonist resulted in a significant contractile response. However, the magnitude and nature of the response were dependent upon the stage of the estrous cycle, with responses to all agonists being significantly decreased in tissue from proestrus and estrus. Furthermore, the nature of NK3-R-mediated contraction was different in tissue from proestrus and estrus compared to metestrus and diestrus. The hormonal dependence of NK-R-mediated contractility was then examined in the ovariectomized estrogen-supplemented rat model. These studies confirmed that the magnitude and nature of uterine contractility in response to NK-R activation depend upon the hormonal environment.

Multiple mechanisms of heterologous beta-adrenoceptor regulation in rat uterus.

The inhibitory effects of catecholamines on rat myometrium mediated by beta-adrenoceptors are modulated by ovarian steroids. Previously reported findings of radioligand binding studies on myometrial membranes have demonstrated changes in the numbers of beta-adrenergic binding sites following ovarian steroid treatment. However, these changes were not accompanied by parallel functional changes. In the present study, we have investigated possible mechanisms of heterologous beta-adrenoceptor regulation by ovarian steroids. Binding studies were performed on myometrial membrane and cytosolic preparations from rats which had been ovariectomized and subsequently received no hormonal treatment or had been treated with oestradiol, progesterone or combined oestradiol and progesterone. The beta-adrenergic antagonist [125I]iodocyanopindolol and the unlabelled competing agonist, isoprenaline, were used in the present studies. Hormonal treatment had no effect on the concentration of beta-adrenergic binding sites in the myometrium (i.e. the number of membrane-bound and cytosolic binding sites per mg protein). However, significant changes were found in the total number of binding sites; these were associated with the hormone-induced tissue hypertrophy. In myometrium from ovariectomized-alone rats, approximately 50% of beta-adrenergic binding sites were present in the cytosolic fraction. Oestradiol treatment, either on its own or in combination with progesterone, resulted in the translocation of binding sites to the cell membrane. However, in the absence of progesterone only 33% of the membrane-bound binding sites bound the beta-adrenergic agonist, isoprenaline, with a high affinity, suggesting that the majority of these membrane-bound binding sites represented non-functional beta-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of denervation on muscarinic receptors in the rat bladder.

OBJECTIVE: To demonstrate the specific distribution of muscarinic receptors in the rat urinary bladder and to investigate the effects of afferent and efferent denervation on the density and distribution of muscarinic receptors. MATERIALS AND METHODS: Urinary bladders were obtained from female rats which had been injected with vehicle (control), or neonatally with capsaicin (NC, afferent denervation) or which had their pelvic plexus removed (post-ganglionic denervation, PGD, efferent denervation). Tissue sections were used in radioligand-binding studies and for autoradiography with the muscarinic receptor ligand l-quinuclidinyl[phenyl-4-3H]benzilate (QNB). RESULTS: Binding of QNB was saturable and specific to a single population of binding sites, with a mean dissociation constant (Kd) of 1.05 +/- 0.14 nM in controls and 0.90 +/- 0.13 nM in rats with PGD. Post-ganglionic denervation caused a 37% increase in maximal binding (Bmax) of QNB from 437.1 +/- 39.1 fmol/mg protein (control group) to 599.1 +/- 4.5 fmol/mg protein (P < 0.02). Autoradiograms revealed muscarinic binding sites over the smooth muscle, but none over the epithelium. Smooth muscle binding sites were doubled after PGD but were unchanged after NC treatment. CONCLUSION: Muscarinic receptors were localized over the smooth muscle of the rat bladder and were increased after post-ganglionic denervation. This increase may be responsible for the increased sensitivity to muscarinic agonists reported to occur after bladder denervation.

The effect of acidosis on beta-adrenergic receptors in ferret cardiac muscle.

Acidosis decreases the force of contraction of cardiac muscle in response to noradrenaline. The role of beta-adrenergic receptors in this response to acidosis was investigated. Radioligand techniques were used to determine beta-adrenergic receptor number and the degree of G-protein coupling, and to see whether these were altered in tissues subject to acidosis. The effect of pH on agonist and antagonist binding to these receptors was also investigated. Tissue pre-exposure to acidic conditions had no effect on numbers of beta-adrenergic receptors and no effect on the affinity of [125I]iodocyanopindolol (ICYP) for the receptors. Agonist competition experiments indicated that there was no change in the affinity of isoprenaline for these receptors, and there was no change in the relative proportions of high and low affinity binding sites. When radioligand experiments were performed under acidic conditions, however, the total number of beta-adrenergic receptors increased, and the affinity of these receptors for isoprenaline increased. This increase in agonist affinity might, therefore, minimize the shift to the right seen in the dose-response curve to noradrenaline during acidosis.

The presence of NK3 tachykinin receptors on rat uterus.

The NK3 agonist, senktide, induced a potent contraction of rat uterus in the presence of tetrodotoxin, atropine and indomethacin, or the tachykinin receptor antagonists L-659877 and [D-Pro4,D-Trp7,9,10]substance P (4-11). Additional contractile and radioligand binding studies with receptor selective agonists and antagonists confirmed the presence of NK3 receptors and also revealed the presence of NK1 and NK2 receptors. The rat uterus is the second peripheral tissue in which a post-synaptic, non-neuronal NK3 receptor has been identified.

Beta adrenoceptors in human nasal mucosa.

The significance of the beta adrenergic system in the nasal mucosa is unclear. The authors have used the technique of autoradiography to localize and classify beta adrenoceptors in human nasal mucosa. The receptors have been found to be exclusively of the beta-2 subtype and the highest density is found in the glandular ducts. It is suggested that the beta-adrenergic system may have a physiologically important role in controlling the electrolyte composition of nasal secretions.

The autoradiographic localization of calcitonin gene-related peptide and substance P receptors in human fallopian tube.

The binding of [125I] human alpha calcitonin gene-related peptide (hCGRP) and [125I]Bolton-Hunter-labelled substance P (BH-SP) to human fallopian tube tissue sections was characterized and the respective binding sites were localized by light-microscopic autoradiography. The hCGRP binding sites were associated with the muscularis, lamina propria and vascular smooth muscle, the latter being the most intensely labelled. BH-SP binding sites were associated only with blood vessels. This labelling was intense, and appeared to be restricted to the vascular endothelium. These results suggest that calcitonin gene-related peptide and substance P may act together to regulate local blood flow and plasma extravasation.

The presence of beta-adrenoceptors in rat endometrium is dependent on circulating oestrogen.

It has been proposed that the change in sensitivity of the uterus to catecholamines during the oestrous cycle may result from changes in beta-adrenoceptor density in the myometrium. In the present work we applied the technique of light-microscopic autoradiography using the radioligand [125I]iodocyanopindolol to study the density and distribution of beta-adrenoceptors in the rat uterus during the normal oestrous cycle, following ovariectomy, and after ovariectomy with oestradiol replacement. We found that beta-adrenoceptor density in the endometrium, but not the myometrium, varied during the oestrous cycle, being highest during pro-oestrous. The endometrium of the ovariectomized rats was devoid of any beta-adrenoceptors, whilst that of the oestradiol-treated rats was very intensely labelled. Following ovariectomy there was an increase in beta-adrenoceptor density in the myometrium, but this was not observed in the animals given oestradiol replacement. It appears that both the presence and density of beta-adrenoceptors in rat endometrium is dependent on circulating oestrogens.

The distribution of beta-adrenoceptors in human cervix.

The distribution of beta-adrenoceptors in sections of human cervix taken at the proliferative phase of the menstrual cycle was studied using light-microscopic autoradiography. The radioligand [125I]iodocyanopindolol (125ICYP) was used to identify specific binding sites. Moderate density of labelling by 125ICYP was seen over smooth muscle and blood vessels. The most intense labelling, however, was seen over glands and surface columnar epithelium. The association of beta-adrenoceptors with glands and surface columnar epithelium suggests a possible adrenergic regulation of secretory function in the cervix.

A comparison of the distribution of substance P and calcitonin gene-related peptide receptors in the rat bladder.

Binding of [125I]Bolton-Hunter labelled substance P (BH-SP) and [125I]human alpha-calcitonin gene-related peptide (h alpha CGRP) to rat bladder tissue sections was characterized and the respective binding sites localized by light-microscopic autoradiography. BH-SP binding sites were localized to epithelium, blood vessels and smooth muscle while hCGRP binding sites were present only over the epithelium. These results suggest that the range of biological actions of substance P and calcitonin gene-related peptide, which may be co-released from the same afferent terminals, might be determined by the different distributions of their respective receptors.

Autoradiographic visualization of beta-adrenoceptor subtypes in human lung.

Adrenoceptor subtypes have been localized in human lung by an autoradiographic method, using [125I]iodocyanopindolol (ICYP) to label beta-receptors in tissue sections. The ICYP was incubated with cryostat sections of microscopically normal human lung method on microscope slides for 2 h at 37 degrees C. Nonspecific binding was determined by incubating adjacent serial sections in the presence of 200 microM (-)-isoproterenol. Specific binding, which accounted for greater than 90% of total counts bound to the sections, was saturable, of high affinity, and stereoselective, having the same pharmacologic characteristics as binding to homogenates prepared from the same lungs. Competition with selective beta-receptor antagonists ICI 118,551 (beta 2-selective) and betaxolol (beta 1-selective) showed that the ratio of beta 2 to beta 1-receptors in the sections was approximately 3:1. Autoradiography revealed that beta-receptors were widely distributed, with dense labeling over airway epithelium, alveolar walls, and submucosal glands, and a lower density of grains over airway and vascular smooth muscle. The beta-receptors of airway smooth muscle from large and small airways were entirely of the beta 2-receptor subtype, which is consistent with functional studies. Similarly, beta-receptors of airway epithelium and vascular smooth muscle were also entirely of the beta 2-receptor subtype. In bronchial submucosal glands and alveolar walls, both receptor subtypes appeared to coexist with beta 2-receptors, making up 10% of the total in glands and 30% in alveoli. The significance of beta 1- and beta 2-receptors in alveolar walls (which account for greater than 90% of total beta-receptors in human lung) remains to be determined.