Frequently applied ketamine, medetomidine and thiopental anaesthesia induces high mortality in Wistar rats.

OBJECTIVE: Fatal reactions to the combination of ketamine-medetomidine and thiopental in Wistar rats are described in two different models of orthodontic tooth movement. MATERIALS AND METHODS: Thirty male rats were divided into two groups that required repeated anaesthesia during a 42-day study period, once a week or more frequently depending on the experimental group. The combination of ketamine [50 mg/kg body weight (b.w.)] and medetomidine (67 µg/kg b.w.) was administered intraperitoneally. Thiopental (8.3 mg/kg b.w.) was administered intraperitoneally 5 minutes later, barring any observable adverse reactions to the anaesthesia. RESULTS: Twelve animals died, though none during the first two procedures. Three animals died shortly after the administration of a ketamine-medetomidine combination, and the remainder died 10-25 minutes later. Only four of the affected animals received thiopental before their death on a particular day. As ten rats died in the more frequently anaesthetized group, repeated anaesthesia was suspected to be the cause of the increased mortality. CONCLUSIONS: Obstruction of the respiratory airways by saliva with subsequent suffocation may have been one of the causes of death, as it appeared in all the affected animals. Although the combination of ketamine and an alpha-2 adrenergic agonist is generally considered to be safe in rats, we propose that studies utilizing protocols requiring repeated anaesthesia adhere to a minimum safety period of 8.5 days between anaesthesia events. Alternative anaesthetic protocols should be employed if adherence to this is not possible due to the nature of the study.

Double unilateral fenestration of the anterior cerebral artery in the pre-communicating segment: a report of a unique case.

A unique example of two fenestrations of the pre-communicating (A1) segment of the right anterior cerebral artery (ACA) in a 78-year-old woman was a special case among 388 cadaveric specimens. It was found by a retrospective review of the personal data obtained during graduate and undergraduate studies at the Faculty of Medicine. Two unequal fenestrations of the right A1 segment were associated with the presence of a pseudo anterior communicating artery, hypoplasia of the right posterior communicating artery and the left superior cerebellar artery, absence of the right anterior inferior cerebellar artery, and ectasia of the basilar artery; however, the cerebral arteries were without aneurysm(s) or other pathology. The reason could be the almost equal ACA diameter on both sides.

Periodontal ligament regulatory role in experimental diabetic rat model of periodontium remodelling.

BACKGROUND: Diabetes, among multiple systemic harmful health issues, also may deteriorate normal regenerative and reparative functions of periodontium. The aim of this research was to study the role of periodontal ligament in tissue remodelling under the orthodontic appliance stimulation in two rat experimental models (healthy Wistar rats and Goto-Kakizaki, rodent model of non-obese type 2 diabetes). MATERIALS AND METHODS: Four groups of rats were defined: Wistar (WI; n = 8) and Goto-Kakizaki (GK; n = 8) control groups without orthodontic appliances, and Wistar (n = 16) and Goto-Kakizaki (n = 16) appliance groups with orthodontic appliances. After 42 days, rats were sacrificed and histopathology descriptive analysis about periodontal ligament and adjacent structures was performed as well as cellularity of periodontal ligament and Kappa curvature of tooth roots were measured. RESULTS: Goto-Kakizaki control rats showed statistically significantly higher cellularity in comparison with Wistar control rats (p < 0.001). Both applied groups (WI 44.63 ± 6.68; GK 79.58 ± 10.06) also showed statistically significantly higher cellularity (p < 0.001) in comparison with control groups (WI 34.48 ± 6.92; GK 45.31 ± 11.18). Applied groups (WI 0.197 ± 0.2; GK 0.126 ± 0.083) had statistically significant higher values of Kappa curvature in comparison with control groups (WI 0.023 ± 0.011; GK 0.037 ± 0.011) (WI appliance vs. WI control: p < 0.001; GK appliance vs. GK control: p < 0.05). Agitated periodontal ligament caused different degrees of cementoclasia and additionally dentinoclasia, altering the natural root curvature. CONCLUSIONS: Although not significantly different (WI and GK appliance groups) according to degree of molar roots odontoclasia, higher cellularity of agitated GK periodontal ligament could be influencing factor for, as previously reported, elevated osteoclast mobilization and possible prolonged periodontium reconstitution.

The role of endothelin B receptor in bone modelling during orthodontic tooth movement: a study on ETB knockout rats.

The endothelin system has an important role in bone modelling during orthodontic tooth movement (OTM); however, little is known about the involvement of endothelin B receptors (ETB) in this process. The aim of this study was to evaluate the role of ETB in bone modelling during OTM using ETB knockout rats (ETB-KO). Thirty-two male rats were divided into 4 groups (n = 8 per group): the ETB-KO appliance group, ETB-KO control group, wild type (ETB-WT) appliance group, and ETB-WT control group. The appliance consisted of a super-elastic closed-coil spring placed between the first and second left maxillary molar and the incisors. Tooth movement was measured on days 0 and 35, and maxillary alveolar bone volume, osteoblast, and osteoclast volume were determined histomorphometrically on day 35 of OTM. Next, we determined the serum endothelin 1 (ET-1) level and gene expression levels of the osteoclast activity marker cathepsin K and osteoblast activity markers osteocalcin and dentin matrix acidic phosphoprotein 1 (DMP1) on day 35. The ETB-KO appliance group showed significantly lower osteoblast activity, diminished alveolar bone volume and less OTM than the ETB-WT appliance group. Our results showed that ETB is involved in bone modelling in the late stage of OTM.

Satisfaction with facial profile aesthetics: are norms overrated?

This study aimed to explore to what extent adults perceive deviations from the norm of a balanced profile with normal occlusion as reducing satisfaction with facial appearance and having a psychosocial impact. This cross-sectional study included 225 Caucasian subjects (64% women) aged 18-42 years. Their facial profiles were analyzed photogrammetrically and they were classified into three categories: within, below, or above the standard range for the Croatian population with a normal occlusion. Psychosocial issues were assessed by self-reported satisfaction with facial appearance and domains from the Orthognathic Quality of Life Questionnaire: social aspects of dentofacial aesthetics (SA), facial aesthetics concern (FA), and awareness of dentofacial aesthetics (AW). Men with a concave profile were less satisfied with their faces than those with a flat or convex profile (P<0.05). A reduced upper lip height in men resulted in a lower level of satisfaction and increased FA score, when compared to men with a normal or increased upper lip height (P<0.05). In women, a reduced middle third of the face increased AW (P=0.045). Deviations from a well-balanced facial profile, as well as the morphology of the nose and lip, do not increase psychosocial issues to a great extent. The range of acceptable facial characteristics is evidently much broader than the norms.

Expression levels of endothelin-1, endothelin-2, and endothelin-3 vary during the initial, lag, and late phase of orthodontic tooth movement in rats.

Endothelins (ET)-1, ET-2, and ET-3 are one group of cytokines likely to be released during orthodontic tooth movement (OTM). Therefore, the expression of ET levels was investigated to determine the importance and involvement of isopeptides during the several phases of OTM. Thirty-two male Wistar rats (12-13 weeks old) were divided into four groups of eight: control, 14, 28, and 42 day groups. Tooth movement was induced by a closed-coil spring inserted between the upper left first molar and the upper incisors. The distance between the teeth was measured on days 0, 2, 7, 14, 21, 28, 35, and 42 using a digital calliper. The rate of tooth movement was calculated. The animals were sacrificed on days 14, 28, and 42 and gene expression levels of all three ET were determined using reverse transcription polymerase chain reaction. Statistical analysis was performed using two-way analysis of variance, Bonferroni's correction, and paired t-tests. The distance between the teeth decreased in all appliance groups (P < 0.001). The rate of tooth movement was 0.20 +/- 0.02, 0.03 +/- 0.01, and 0.06 +/- 0.02 mm/day between days 0-2, 3-21, and 22-42, respectively. On day 14, gene expression levels for ET-1 (P < 0.05) and ET-3 (P < 0.001) increased compared with day 0. On day 28, a downregulation of ET-3 was observed when compared with day 0 (P < 0.001). On day 42, ET-1 (P < 0.001) and ET-3 (P < 0.01) gene expression levels were strongly upregulated, while ET-2 gene expression level was downregulated (P < 0.01) when compared with day 0. ET-1 and ET-3, but not ET-2, are involved in all three phases of OTM, and ET-1 seems to be the predominant form in the late phase of OTM.

Orthodontic force decreases the eruption rate of rat incisors.

The aim of this study was to determine whether a force applied in an antero-posterior direction would adequately reduce incisor eruption. This is needed to achieve a constant direction of force which is one of the demands for a good model for studying orthodontic tooth movement. Twenty male Wistar rats aged 11-12 weeks were divided into two equal groups: in the appliance group, a superelastic closed coil spring (25 cN) was placed between the upper left first molar and the incisors. The control group consisted of animals without an appliance. In both groups, cuts were created on the labial surfaces of the upper and lower incisors. The distance from the gingival reference point to the midpoint of the cut was measured for 10 days at 2 day intervals. Upper incisor inclination was determined as the distance from the most mesial point of the upper left first molar to the incisal edge of the ipsilateral incisor on days 0 and 10. Statistical analysis was carried out using two-way analysis of variance and a Bonferroni post- test to estimate reliability. The eruption rates of the maxillary incisors in the appliance group were significantly decreased when compared with the control group during the whole experiment. In the appliance group, the eruption rates of the mandibular incisors were decreased more than those of the maxillary incisors (P<0.01). There was no difference in incisor inclination between the appliance and control groups on day 10 (P=0.81). The applied force of 25 cN in an antero-posterior direction diminished incisor eruption to a level which enabled a constant direction of orthodontic force for 10 days.

The effects of TBC3214, a selective endothelin ETA receptor antagonist, on orthodontic tooth movement in rats.

Many chemical messengers are involved in the process of alveolar bone and periodontal ligament remodelling during orthodontic tooth movement. Among them is probably endothelin-1 (ET-1). Its role in this process has been partly explained using tezosentan, which affects endothelin A (ET(A)) and endothelin B (ET(B)) receptors. Tezosentan enhances orthodontic tooth movement. The aim of this study was to determine the possible effects of a highly selective ET(A) antagonist on orthodontic tooth movement in rats. Thirty male Wistar rats, 11-12 weeks of age, divided into three equal groups. In group I, a closed-coil spring was used and they were treated daily with 15 mg/kg body weight of TBC3214, a highly selective ET(A) antagonist. A closed-coil spring was also used in group II and the animals were treated daily with a placebo. Group III were treated daily with a placebo. The coil spring delivered a force of 25 cN and was attached between the upper left first molar and upper left incisor. The distance between the teeth was measured with a digital calliper (accuracy +/- 0.01 mm) on days 0, 7, 14, 21, 24, 32, 37, and 40. The differences in the distance between the teeth were calculated to determine the amount of tooth movement. Statistical analysis was performed using two-way analysis of variance, Bonferroni's correction, and paired t-tests. The distance between the upper left first molar and the upper left incisor decreased in groups I and II. In group I, tooth movement was significantly less on days 32 and 37 (P < 0.01) and on day 40 (P < 0.001) compared with group II. In group III, the distance between the teeth increased during the study (P < 0.001). In animals treated daily with TBC3214, tooth movement was significantly less compared with the animals treated with a placebo. It is concluded that ET-1, which is the predominant form of endothelin isopeptides, is involved in orthodontic tooth movement in rats, probably by enhancing bone resorption via ET(A) receptors.