Dimitris Emmanouil

Advances in Understanding the Actions of Nitrous Oxide

Nitrous oxide (N(2)O) has been used for well over 150 years in clinical dentistry for its analgesic and anxiolytic properties. This small and simple inorganic chemical molecule has indisputable effects of analgesia, anxiolysis, and anesthesia that are of great clinical interest. Recent studies have helped to clarify the analgesic mechanisms of N(2)O, but the mechanisms involved in its anxiolytic and anesthetic actions remain less clear. Findings to date indicate that the analgesic effect of N(2)O is opioid in nature, and, like morphine, may involve a myriad of neuromodulators in the spinal cord. The anxiolytic effect of N(2)O, on the other hand, resembles that of benzodiazepines and may be initiated at selected subunits of the gamma-aminobutyric acid type A (GABA(A)) receptor. Similarly, the anesthetic effect of N(2)O may involve actions at GABA(A) receptors and possibly at N-methyl-D-aspartate receptors as well. This article reviews the latest information on the proposed modes of action for these clinical effects of N(2)O.

Reliability and validity of the Greek version of the Children's Fear Survey Schedule–Dental Subscale

BACKGROUND The Childrens Fear Survey Schedule-Dental Subscale (CFSS-DS) is a commonly used questionnaire which measures childrens dental fear. OBJECTIVE The aim of this study was to gather data to evaluate the psychometric properties of a Greek version of the CFSS-DS. METHODS A sample of 260 children aged 4-12 completed the Greek version of the CFSS-DS while in the waiting room of a paediatric dentist. The dentist, who was unaware of the childrens scores, rated the childrens behaviour during the dental appointment using the Frankl scale. Children who returned for a second dental appointment during the study period completed the CFSS-DS a second time. RESULTS The mean CFSS-DS score was 24.80 (standard deviation = 9.17). Age and gender were not related to mean scores. Invasiveness of dental treatment was not related to mean scores. Children who were most uncooperative/fearful on the Frankl had the highest mean scores (Kruskal-Wallis chi2 = 9.48; d.f. = 2; P = 0.009). The internal consistency (Cronbachs alpha) was 0.85, and the test-retest reliability (intraclass correlation) was 0.74. CONCLUSIONS The Greek version of the CFSS-DS appears to be reliable and valid. Further samples should include school samples, to include children who may not go to the dentist.

Nitrous oxide-antinociception is mediated by opioid receptors and nitric oxide in the periaqueductal gray region of the midbrain

Previous studies have shown that nitrous oxide (N(2)O)-induced antinociception is sensitive to antagonism by blockade of opioid receptors and also by inhibition of nitric oxide (NO) production. The present study was conducted to determine whether these occur within the same brain site. Mice were stereotaxically implanted with microinjection cannulae in the periaqueductal gray (PAG) area of the midbrain. In saline-pretreated mice, exposure to 70% N(2)O resulted in a concentration-dependent antinociceptive effect in the mouse abdominal constriction test. Pretreatment with an opioid antagonist in the PAG significantly antagonized the antinociceptive effect. Pretreatment with an inhibitor of NO production in the PAG also significantly antagonized the antinociceptive effect. These findings suggest that N(2)O acts in the PAG via an NO-dependent, opioid receptor-mediated mechanism to induce antinociception.

Giant Cell Fibroma in Children: Report of Two Cases and Literature Review

ABSTRACT Background Giant cell fibroma is a type of fibrous tumour of the oral mucosa which rarely affects children under the age of 10. The purpose of this paper was to contribute two clinically and histologically documented cases of giant cell fibroma in the free gingiva of a 7 and 6 year old boys. Methods Both nodules were presented in the mandibular anterior region. In the differential diagnosis several fibrous hyperplastic lesions were considered such as traumatic fibroma, papilloma, peripheral ossifying fibroma, peripheral odontogenic fibroma, giant cell fibroma and odontogenic hamartoma. Results The lesions were removed and the histological examination revealed fibrocollagenous connective tissue with the presence of stellate giant cells which confirmed the diagnosis of giant cell fibroma. Conclusions Dentists should be aware of the existence of giant cell fibroma in children, which must be included in the differential diagnosis of nodular lesions of the gingiva and adequately diagnosed and treated by removal and histopathological examination.

Psychometric and biohormonal indices of dental anxiety in children. A prospective cohort study

Abstract The stress of dental treatment often elicits negative emotions in children, expressed as dental fear or anxiety. Highly anxious children obstruct treatment and avoid therapy, further amplifying oral health problems. The aim of this study was to examine the neuroendocrine and autonomic nervous system responses to dental treatment and their possible interactions and associations with psychometric indices of anxiety, caries, previous dental experience, anesthesia, age and gender in school children. Upon informed consent, saliva was obtained from 97 children (59% males, mean age ±  SD: 89.73 ± 15 months) in the Clinic of pediatric dentistry before treatment, immediately post-treatment and at the recall visit to determine cortisol and salivary alpha-amylase (sAA) levels. Dental and general anxiety was assessed through specific questionnaires completed by the children. Compared to pre-treatment, cortisol levels were increased following treatment, while sAA levels were higher at the recall. Pre- and post-treatment cortisol and sAA responses were positively correlated. Dental and general anxiety questionnaire scores were also significantly correlated with each other. The integrated autonomic and neuroendocrine responses prior to treatment were correlated with state anxiety and those following treatment with dental anxiety. However, univariable and multivariable linear regression analysis associated post-treatment cortisol, but not sAA, levels with dental anxiety. No associations of cortisol or sAA responses with caries, age, gender, previous dental experience or anesthesia were detected. These data provide some evidence that both sAA and cortisol levels are altered in children in anticipation or during dental treatment, but only cortisol levels are associated to dental anxiety.

A study of the role of serotonin in the anxiolytic effect of nitrous oxide in rodents

RATIONALE In earlier studies, we have shown that nitrous oxide (N2O)-induced behavioral effects in rats and mice are mediated by benzodiazepine receptors. OBJECTIVES This two-part study was conducted in order to investigate the possible role of serotonin (5-HT) in the behavioral effects of N2O by clarifying its effects on regional brain concentrations of 5-HT and assessing the influence of 5-HT antagonist and reuptake inhibiting drugs on the anxiolytic-like behavioral effect of N2O. METHODS In experiment A, male, 150-200 g Sprague-Dawley rats were killed following a 15-min exposure to room air or 70% N2O. The frontal cortex, hippocampus, corpus striatum and hypothalamus were dissected out and analyzed by HPLC with electrochemical detection for content of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA); dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were also measured. In experiment B, male 18-22 g NIH Swiss mice were pretreated with the 5-HT2 antagonist cinanserin, the 5-HT3 antagonist LY-278,584, the 5-HT reuptake inhibitor fluoxetine or saline and tested in the light/dark exploration test under 70% N2O 30 min after pretreatment. RESULTS In experiment A, N2O produced differential effects on 5-HT neurons in distinct brain areas. There was increased 5-HT turnover in the hypothalamus, decreased turnover in the frontal cortex but no changes in either hippocampus or corpus striatum. By comparison, dopamine turnover in these brain regions was unaltered by N2O exposure. In experiment B, pretreatment with neither cinanserin, LY-278,584 nor fluoxetine had any appreciable effect on the N2O-induced increase in time spent in the light compartment. Only cinanserin significantly reduced the N2O-induced increase in transitions. CONCLUSIONS While neurochemical results suggest an effect of N2O on brain 5-HT function, there was no effect of 5-HT2 or 5-HT3 antagonists or 5-HT reuptake inhibitor on N2O-induced anxiolytic-like behavior.

Congenital Adrenal Hyperplasia: A Case Report with Premature Teeth Exfoliation and Bone Resorption

Congenital adrenal hyperplasia (CAH) is an inherited autosomal recessive disorder characterized by insufficient production of cortisol. The aim of this case report was to present a child with CAH, premature exfoliation of primary teeth and accelerated eruption of his permanent teeth related to bone resorption. A 4.5-year-old Caucasian boy with CAH and long-term administration of glucocorticoids was referred for dental restoration. Clinical examination revealed primary molars with worn stainless steel crowns, severe attrition of the upper canines, and absence of the upper incisors. Before the completion of treatment, abnormal mobility of the first upper primary molars and the lower incisors was detected, and a few days later the teeth exfoliated prematurely. Histologic examination revealed normal tooth structure. Alkaline phosphatase and blood cells values were normal. Eruption of the permanent dentition was also accelerated. Tooth mobility was noticed in the permanent teeth as soon as they erupted, along with bone destruction. Examination revealed an elevated level of receptor activator of nuclear factor-κB ligand and lower-than-normal osteoprotegerin and vitamin D levels. The patient was treated with vitamin D supplements, and his teeth have been stable ever since. CAH is a serious chronic disorder appearing in children with accelerated dental development and possibly premature loss of primary teeth.

Hand–Schüler–Christian disease presenting with recurrent, bilateral, symmetrical mandibular lesions in an 8-year-old boy: report of a case

INTRODUCTION Hand-Schüller-Christian disease (HSC) is the unisystem multifocal form of Langerhans Cell Histiocytosis (LCH) and is primarily seen in infants and children. CASE REPORT An 8-year-old boy was referred for acute mandibular pain. His medical history included otic LCH and diabetes insipidus at age of 11 months. Intraorally, a pressure sensitive swelling, and radiographically, extensive bone loss were revealed on the area of lower second primary molars. The primary molars were extracted and histological examination confirmed the final diagnosis of HSC. The patient was treated with chemotherapy and the lesions decreased considerably. Two years later, a new swelling was recorded in the same area bilaterally. Biopsy confirmed recurrent HSC disease and the patient entered an alternative chemotherapy protocol. Six months later, improvement of the lesions was revealed. CONCLUSIONS Dentists can contribute to a timely and valid identification of HSC disease by correctly differentially diagnosing lesions of head and neck.