Gene expression of growth factors with angiogenic potential in human dental pulp tissue from teeth with complete and incomplete root development.

AIM: To quantify the expression of angiogenic growth factors (ANG2, VEGFA, TGFß1) and their corresponding receptors (VEGFR1, VGFR2, NRP1 and TGFßR1) in human dental pulps from extracted third molars with complete and incomplete root development. METHODOLOGY: Fifty-six dental pulp samples obtained from freshly extracted human third molars were divided equally into two groups according to their stage of root development; 28 third molars with complete root development and 28 third molars with incomplete root development. All samples were processed and total RNA was extracted, cDNA was then synthetized for each sample and the target genes expression profiles for ANG2, VEGFA, VEGFR1, VEGFR2, NRP1, TGFß1 and TGFßR1 were obtained by RT2-PCR. The data was analysed with a Student's t-test to compare the replicate ∆∆Ct values for each gene. RESULTS: Teeth with incomplete root development were associated with a significantly greater gene expression of TGFßR1 (P = 0.03), whereas in teeth with complete root development the genes that had significantly greater expression were VEGFA (P = 0.04). CONCLUSION: The angiogenic growth factors (ANG2, VEGFA, TGFß1) and their receptors (NRP1, VEGFR1, VEGFR2 and TGFßR1) were expressed in pulps of teeth with complete and incomplete root development measured by RT2-PCR, with TGFBR1 genes being significantly different in teeth with incomplete root development and VEGFA genes in teeth with complete root development.

Substance P and Calcitonin gene-related peptide expression in human periodontal ligament after root canal preparation with Reciproc Blue, WaveOne Gold, XP EndoShaper and hand files.

AIM: To quantify Substance P (SP) and Calcitonin gene-related peptide (CGRP) expression in healthy human periodontal ligament from premolars after root canal preparation with Reciproc Blue, WaveOne Gold, XP EndoShaper and hand files. METHODOLOGY: A total of 50 human periodontal ligament samples were obtained from healthy mandibular premolars where extraction was indicated for orthodontic reasons. Prior to extraction, 40 of these premolars were equally divided into four groups, and root canals were prepared using four different systems: Reciproc Blue, WaveOne Gold, XP EndoShaper and a hand instrumentation technique. The remaining 10 healthy premolars were extracted without treatment and served as a negative control group. All periodontal ligament samples were processed, and SP and CGRP were measured by radioimmunoassay. The Kruskal-Wallis test was used to establish significant differences between groups and LSD post hoc comparisons were also performed. RESULTS: Greater SP and CGRP values were found in the hand instrumentation group, followed by the XP EndoShaper, WaveOne Gold and the Reciproc groups. The lower SP and CGRP values were for the healthy periodontal ligament group. The Kruskal-Wallis test revealed significant differences between groups (P < 0.05). Post hoc Least Significant Difference (LSD) tests revealed significant differences (P < 0.05) in SP and CGRP expression between all the comparisons except for the Reciproc Blue and WaveOne Gold group (P > 0.05). CONCLUSION: All the root canal preparation techniques tested increased SP and CGRP expression in human periodontal ligament, with hand files and XP EndoShaper instruments being associated with greater neuropeptide release compared to Reciproc Blue and WaveOne Gold files.

Angiogenic mechanisms of human dental pulp and their relationship with substance P expression in response to occlusal trauma.

Angiogenesis is the formation of new blood vessels based on a pre-existing vasculature. It comprises two processes, sprouting of endothelial cells and the division of vessels due to abnormal growth of the microvasculature. It has been demonstrated that substance P (SP) can induce angiogenesis either by modulating endothelial cell growth (direct mechanism) or by attracting cells with angiogenic potential to the injury site (indirect mechanism). Therefore, the purpose of this article is to review the angiogenic mechanisms that regulate mineralized tissue formation in human dental pulp tissue and their relationship with SP expression as a defence response to stimuli such as the masticatory function and occlusal trauma. Articles included in this review were searched in PubMed, Scopus and ISI Web of Science databases, combining the following keywords: human dentine pulp, angiogenesis, angiogenic growth factors, neuropeptides, substance P, neurogenic inflammation, dentine matrix, dentinogenesis, occlusal trauma and dental occlusion. It is concluded that human dental pulp tissue responds to occlusal trauma and masticatory function with a neurogenic inflammatory phenomenon in which SP plays an important role in the direct and indirect mechanisms of angiogenesis by the action evoked via NK1 receptors at different cells, such as fibroblasts, endothelial and inflammatory cells, leading to new blood vessel formation which are needed to stimulate mineralized tissue formation as a defence mechanism.

The influence of two reciprocating single-file and two rotary-file systems on the apical extrusion of debris and its biological relationship with symptomatic apical periodontitis. A systematic review and meta-analysis.

This systematic review and meta-analysis investigated the influence of the number of files (full-sequence rotary-file versus reciprocating single-file systems) used during root canal preparation on the apical extrusion of debris and its biological relationship with the occurrence of symptomatic apical periodontitis. An extensive literature research was carried out in the Medline, ISI Web of Science and Cochrane databases, for relevant articles with the keyword search strategy. Based on inclusion and exclusion criteria, two reviewers independently rated the quality of each study determining the level of evidence of the articles selected. The primary outcome for the meta-analysis was determined by the amount of debris extruded into the periapical tissue during root canal preparation with multiple- or single-file systems in four laboratory studies. Analysis of in vivo release of neuropeptides (SP and CGRP) after root canal preparation with single- or multiple-file systems was also carried out. Amongst the 128 articles initially found, 113 were excluded for being nonrelevant or not fulfilling the selection criteria. Another four articles were excluded after methodology evaluation. Finally, nine laboratory studies and two in vivo studies were included in the systematic review. Four of the laboratory studies were further included for meta-analysis that revealed greater debris extrusion after the use of single-file techniques when compared to multiple-file systems. Analysis of in vivo neuropeptide expression in the periodontal ligament suggests that the design of the instrument is more important than the number of files used. Both rotary and reciprocating single-file systems generate apical extrusion of debris in laboratory studies, or expression of neuropeptides in vivo. Available evidence is limited, but supports the fact that this inflammatory reaction is not influenced by the number of files but the type of movement and the instrument design.

The effect of single-file reciprocating systems on Substance P and Calcitonin gene-related peptide expression in human periodontal ligament.

AIM: To quantify the effect of two single-file reciprocating root canal preparation systems on Substance P (SP) and Calcitonin gene-related peptide (CGRP) expression in healthy human periodontal ligament (PDL). METHODOLOGY: Forty PDL samples were obtained from healthy premolars where extraction was indicated for orthodontic reasons. Prior to extraction, 20 of these premolars were divided equally in two groups, and then, root canals were prepared using one of two different single-file systems: WaveOne and Reciproc. Ten premolars were prepared with hand files and served as a positive control group. The remaining 10 premolars where extracted without treatment and served as a negative control group. All PDL samples were processed, and SP and CGRP were measured by radioimmunoassay. RESULTS: Greater SP and CGRP expression were found in the hand instrumentation group (1.220 pmol SP and 0.084 pmol CGRP per mg of PDL), followed by the WaveOne group (0.908 pmol SP and 0.046 pmol CGRP per mg of PDL) and the Reciproc group (0.511 pmol SP and 0.022 pmol CGRP per mg of PDL). The lower SP and CGRP values were associated with the intact control group (0.453 pmol SP and 0.018 pmol CGRP per mg of PDL). The Kruskal-Wallis test revealed significant differences between groups (P < 0.001). Post hoc Tukey HSD tests revealed significant differences in SP and CGRP expression between intact teeth in the control group and all the other groups (P < 0.001) except with the Reciproc group (P = 0.165 and P = 0.42 for SP and CGRP, respectively). Hand instrumentation was associated with significant differences with all the other groups (P < 0.001). Differences between the WaveOne and Reciproc groups were also significant (P < 0.001). CONCLUSION: Substance P and CGRP expression in PDL cells increased when teeth were prepared with WaveOne as well as with hand instrumentation. Reciproc maintained SP and CGRP levels in line with the negative control group.

Effect of intravenous fluid therapy on postoperative vomiting in children undergoing tonsillectomy.

BACKGROUND: Postoperative vomiting (POV) is one of the most frequent complications of tonsillectomy in children. The aim of this study was to evaluate the antiemetic effect of super-hydration with lactated Ringer's solution in children undergoing elective otorhinolaryngological surgery. METHODS: One hundred ASA I-II children, aged 1-12 yr, undergoing elective tonsillectomy, with or without adenoidectomy, under general anaesthesia were studied. Induction and maintenance of anaesthesia were standardized with fentanyl, mivacurium, and sevoflurane in N(2)O/O(2). Subjects were assigned to one of the two groups: 10 ml kg(-1) h(-1) lactated Ringer's solution or 30 ml kg(-1) h(-1) lactated Ringer's solution. A multivariable logistic regression was used for assessing the effects of super-hydration on POV (defined as the presence of retching, vomiting, or both). A value of P<0.05 was considered statistically significant. RESULTS: During the first 24 h postoperative, the incidence of POV decreased from 82% to 62% (relative reduction of 24%, P=0.026). In the adjusted logistic regression model, subjects in the 10 ml kg(-1) h(-1) group had an odds ratio of POV that was 2.92 (95% confidence interval: 1.14, 7.51) for POV compared with subjects in the 30 ml kg(-1) h(-1) group. CONCLUSIONS: Intraoperative administration of 30 ml kg(-1) h(-1) lactated Ringer's solution significantly reduced the incidence of POV during the first 24 h postoperative. Our results support the use of super-hydration during tonsillectomy, as an alternative way to decrease the risk of POV in children.

Evaluation of the effect of intravenous lidocaine on propofol requirements during total intravenous anaesthesia as measured by bispectral index.

BACKGROUND: I.V. lidocaine is increasingly used as an adjuvant during general anaesthesia. The aim of this study was to evaluate the effect of i.v. lidocaine in reducing propofol anaesthetic requirements during total i.v. anaesthesia (TIVA) maintenance and to evaluate its effect on early recovery from anaesthesia. METHODS: Forty adult patients undergoing elective laparoscopic cholecystectomy under TIVA were randomly allocated into the lidocaine group (administered 1.5 mg kg(-1) i.v. lidocaine over 5 min followed by 2 mg kg(-1) h(-1)) and the control group (administered an equal volume of saline). Propofol was administered using a target-controlled infusion to maintain the bispectral index values between 40 and 60. After surgery, all infusions were discontinued and the time to extubation was recorded. Serial arterial blood samples were drawn to assess drug plasma levels. RESULTS: The maintenance dose of propofol was significantly lower in the lidocaine group [6.00 (0.97) mg kg(-1) h(-1)] vs the control group [7.25 (1.13) mg kg(-1) h(-1); P=0.01]. Propofol plasma levels measured at the end of the infusion were 3.71 (0.89) µg ml(-1) in the lidocaine group and 3.67 (1.28) µg ml(-1) in the control group (P=0.91). The median time to extubation was longer (11.0 min; range: 10.0-21.0) in the lidocaine group vs the control group (8.3 min; range: 5.5-12.5; P=0.02). CONCLUSIONS: I.V. lidocaine reduces propofol requirements during the maintenance phase of TIVA, particularly during surgical stimulation. This sparing effect is associated with an increased time to extubation. Owing to its effect on early recovery from anaesthesia, i.v. lidocaine should be taken into account when used as a component of i.v. anaesthesia.

Nitrous oxide (N(2)O) reduces postoperative opioid-induced hyperalgesia after remifentanil-propofol anaesthesia in humans.

BACKGROUND: The aim of this study was to test if intraoperative administration of N(2)O during propofol-remifentanil anaesthesia prevented the onset of postoperative opioid-induced hyperalgesia (OIH). METHODS: Fifty adult ASA I-II patients undergoing elective open septorhinoplasty under general anaesthesia were studied. Anaesthesia was with propofol, adjusted to bispectral index (40-50), and remifentanil (0.30 µg kg(-1) min(-1)). Patients were assigned to one of the two groups: with N(2)O (70%) and without N(2)O (100% oxygen). Mechanical pain thresholds were measured before surgery and 2 and 12-18 h after surgery. Pain measurements were performed on the arm using hand-held von Frey filaments. A non-parametric analysis of variance was used in the von Frey data analysis. P<0.05 was considered statistically significant. RESULTS: Baseline pain thresholds to mechanical stimuli were similar in both groups, with mean values of 69 [95% confidence interval (CI): 50.2, 95.1] g in the group without N(2)O and 71 (95% CI: 45.7, 112.1) g in the group with N(2)O. Postoperative pain scores and cumulative morphine consumption were similar between the groups. The analysis revealed a decrease in the threshold value in both groups. However, post hoc comparisons showed that at 12-18 h after surgery, the decrease in mechanical threshold was greater in the group without N(2)O than the group with N(2)O (post hoc analysis with Bonferroni's correction, P<0.05). CONCLUSIONS: Intraoperative 70% N(2)O administration significantly reduced postoperative OIH in patients receiving propofol-remifentanil anaesthesia.

Influence of obesity on propofol pharmacokinetics: derivation of a pharmacokinetic model.

BACKGROUND: The objective of this study was to develop a pharmacokinetic (PK) model to characterize the influence of obesity on propofol PK parameters. METHODS: Nineteen obese ASA II patients undergoing bariatric surgery were studied. Patients received propofol 2 mg kg(-1) bolus dose followed by a 5-20-40-120 min, 10-8-6-5 mg kg(-1) h(-1) infusion. Arterial blood samples were withdrawn at 1, 3, 5 min after induction, every 10-20 min during propofol infusion, and every 10-30 min for 2 h after stopping the propofol infusion. Arterial samples were processed by high-performance liquid chromatography. Time-concentration data profiles from this study were pooled with data from two other propofol PK studies available at http://www.opentci.org. Population PK modelling was performed using non-linear mixed effects model. RESULTS: The study involved 19 obese adults who contributed 163 observations. The pooled analysis involved 51 patients (weight 93 sd 24 kg, range 44-160 kg; age 46 sd 16 yr, range 25-81 yr; BMI 33 sd 9 kg m(-2), range 16-52 kg m(-2)). A three-compartment model was used to investigate propofol PK. An allometric size model using total body weight (TBW) was superior to all other models investigated (linear TBW, free fat mass, lean body weight, normal fat mass) for all clearance parameters. Variability in V2 and Q2 was reduced by a function showing a decrease in both parameters with age. CONCLUSIONS: We have derived a population PK model using obese and non-obese data to characterize propofol PK over a wide range of body weights. An allometric model using TBW as the size descriptor of volumes and clearances was superior to other size descriptors to characterize propofol PK in obese patients.

The effect of dentine-bonding agents on substance P release in human dental pulp.

AIM: To quantify the effect of dentine-bonding agents on Substance P (SP) release in healthy human dental pulp tissue. METHODOLOGY: Forty pulp samples were obtained from healthy pre-molars where extraction was indicated for orthodontic reasons. In thirty of these pre-molars, a standardized Class V cavity preparation was performed, and teeth were divided equally into three groups: (i) Unetched-cavity control group: Class V cavities only; (ii) Experimental Group I: 'One-step' self-etch bonding agent was placed in the cavity; and (iii) Experimental Group II: 'Two-step' total-etch bonding agent was placed in the cavity. The remaining ten healthy pre-molars where extracted without treatment and served as an intact-teeth control group. SP was measured by radioimmunoassay. RESULTS: Greater SP release was found in the 'one-step' bonding agent group, followed by the 'two-step' bonding agent group and the unetched-cavity control group. The lower SP values were for the intact-teeth control group. anova showed statistically significant differences between groups (P = 0.0001). Tukey HSD post hoc tests showed statistically significant differences in SP release between the intact-teeth control group and the three other groups (P < 0.01) and between the unetched-cavity control group and the 'one-step' bonding agent group (P < 0.05). No significant difference was found between the 'two-step' bonding agent and the unetched-cavity control group. CONCLUSION: Dentine-bonding agents placed over Class V cavity preparations increased SP release. One-step dentine-bonding agents increased SP release most.

Predictive ability of propofol effect-site concentrations during fast and slow infusion rates.

BACKGROUND: The performance of propofol effect-site pharmacokinetic models during target-controlled infusion (TCI) might be affected by propofol administration rate. This study compares the predictive ability of three effect-site pharmacokinetic models during fast and slow infusion rates, utilizing the cerebral state index (CSI) as a monitor of consciousness. METHODS: Sixteen healthy volunteers, 21-45 years of age, were randomly assigned to receive either a bolus dose of propofol 1.8 mg/kg at a rate of 1200 ml/h or an infusion of 12 mg/kg/h until 3-5 min after loss of consciousness (LOC). After spontaneous recovery of the CSI, the bolus was administered to patients who had first received the infusion and vice versa. The study was completed after spontaneous recovery of CSI following the second dose scheme. LOC was assessed and recorded when it occurred. Adequacies of model predictions during both administration schemes were assessed by comparing the effect-site concentrations estimated at the time of LOC during the bolus dose and during the infusion scheme. RESULTS: LOC occurred 0.97 +/- 0.29 min after the bolus dose and 6.77 +/- 3.82 min after beginning the infusion scheme (P<0.05). The Ce estimated with Schnider (ke0=0.45/min), Marsh (ke0=1.21/min) and Marsh (ke0=0.26/min) at LOC were 4.40 +/- 1.45, 3.55 +/- 0.64 and 1.28 +/- 0.44 microg/ml during the bolus dose and 2.81 +/- 0.61, 2.50 +/- 0.39 and 1.72 +/- 0.41 microg/ml, during the infusion scheme (P<0.05). The CSI values observed at LOC were 70 +/- 4 during the bolus dose and 71 +/- 2 during the infusion scheme (NS). CONCLUSION: Speed of infusion, within the ranges allowed by TCI pumps, significantly affects the accuracy of Ce predictions. The CSI monitor was shown to be a useful tool to predict LOC in both rapid and slow infusion schemes.

Prospective evaluation of the time to peak effect of propofol to target the effect site in children.

BACKGROUND: The plasma-effect site equilibration rate constant (k(e0)) of propofol has been determined in children with the use of the time to maximum effect (t(peak)), however, it has not been validated. The objective was to measure the t(peak;) of propofol with two depths of anesthesia monitors in children and to evaluate these measurements with a target-controlled infusion (TCI) system. METHODS: Unpremedicated, ASA I children from 3 to 11 years were studied. In Part 1, children were monitored simultaneously with the bispectral index (BIS) and the A-Line ARX-index (AAI) from the Alaris A-Line auditory-evoked potential monitor/2. The t(peak) after a bolus dose of propofol was measured. In Part 2, the t(peak) measured was used to target the effect site with a TCI system. The median (MD) and the absolute median (MDA) difference between the predicted time of peak concentration at the effect site (Ce) and the measured time of peak effect in the index of depth of anesthesia (t(error)) was used to evaluate the performance of the system. RESULTS: The BIS recordings were of a better quality than the AAI. The mean +/- standard deviation t(peak) was 65 +/- 14 s with the BIS (n=25) and 201 +/- 74 s with the AAI (n=10)(P<0.001). Validation was only performed with the BIS monitor in 40 children, yielding an MD t(error) of -9.5 s and an MDA t(error) of 10.0 s. CONCLUSIONS: The small delay between the evolution of Ce of propofol and the observed effect suggests that this can be a useful model to target the effect site in children.

Propofol consumption and recovery times after bispectral index or cerebral state index guidance of anaesthesia.

BACKGROUND: We compared the propofol requirements and recovery times when either the bispectral index (BIS) monitor or the cerebral state monitor (CSM) is used to guide propofol anaesthesia. METHODS: Forty patients undergoing laparoscopic cholecystectomy were studied. All patients were monitored with both monitors and were randomly allocated into two groups according to the monitor used to titrate propofol administration. Propofol was administered to maintain BIS or CSM within 40 and 60. Propofol consumption and clinical markers of recovery were assessed after surgery. RESULTS: In the CSM group, the values of cerebral state index (CSI) and BIS were 47 (5) and 38 (6), respectively (P=0.00054). In the BIS group, the values of CSI and BIS were 47 (5) and 45 (2), respectively (P=0.15). In the BIS group, the total amount of propofol used was lower [109 (20) microg kg(-1) min(-1)] than in the CSM group [130 (27) microg kg(-1) min(-1)] (P=0.018). The time to eye opening was lower in the BIS [7.2 (3.5) min] than in the CSM group [10.7 (6.6)] (P=0.038). There were no differences in fentanyl consumption, or in other clinical markers of recovery. CONCLUSIONS: Compared with BIS, propofol anaesthesia guided with CSI resulted in 20% higher propofol doses. This, however, does not lead to clinically relevant differences in recovery times.

Expression of insulin-like growth factor-1 and proliferating cell nuclear antigen in human pulp cells of teeth with complete and incomplete root development.

AIM: To quantify the expression of insulin-like growth factor-1 (IGF-1) and proliferating cell nuclear antigen (PCNA) in human pulp cells of teeth with complete or incomplete root development, to support the specific role of IGF-1 in cell proliferation during tooth development and pulp reparative processes. METHODOLOGY: Twenty six pulp samples were obtained from freshly extracted human third molars, equally divided in two groups according to root development stage (complete or incomplete root development). All samples were processed and immunostained to determine the expression of IGF-1 and PCNA in pulp cells. Sections were observed with a light microscope at 80x and morphometric analyses were performed to calculate the area of PCNA and IGF-1 immunostaining using digital image software. Mann-Whitney's test was used to determine statistically significant differences between groups (P < 0.05) for each peptide and the co-expression of both. RESULTS: Expression of IGF-1 and PCNA was observed in all human pulp samples with a statistically significant higher expression in cells of pulps having complete root development (P = 0.0009). CONCLUSION: Insulin-like growth factor-1 and PCNA are expressed in human pulp cells, with a significant greater expression in pulp cells of teeth having complete root development.

Estimation of the plasma effect-site equilibration rate constant (ke0) of rocuronium by the time of maximum effect: a comparison with non-parametric and parametric approaches.

BACKGROUND: The first order plasma-effect-site equilibration rate constant (k(e0)) links the pharmacokinetics (PK) and pharmacodynamics (PD) of a given drug. For the calculation of the k(e0), one method uses a single point of the response curve corresponding to the time to peak effect of a drug (t(peak)); however, it has not been validated. This study compares the k(e0) calculated with the method of t(peak) and the k(e0) calculated with traditional non-parametric and parametric methods. METHODS: Fifteen adult patients receiving total intravenous anaesthesia (TIVA) were studied. All patients were monitored with an NMT Monitor 221 (GE Healthcare, Helsinki, Finland) to obtain the evoked compound EMG of the adductor pollicis to a train-of-four stimuli at 10 s intervals. During TIVA, rocuronium 0.15 mg kg(-1) was given i.v. as a bolus, and the neuromuscular response was recorded until recovery from block. Using the t(peak) and the complete response curve, k(e0) of rocuronium was calculated with the three methods using the predicted plasma concentrations of rocuronium from a PK model. Values of k(e0) are median (range). RESULTS: The k(e0)s obtained were 0.19 min(-1) (0.09-0.72) with the 't(peak)' method, 0.20 min(-1) (0.14-0.44) with the non-parametric method, and 0.19 min(-1) (0.11-0.38) [typical value (range)] with the parametric method (NS). CONCLUSIONS: If the t(peak) can be adequately estimated from the data, the 't(peak) method' is a valid alternative to traditional methods to calculate the k(e0).

Vasoactive intestinal peptide receptor expression in chronic periapical lesions.

AIM: To use radioreceptor analysis for evaluating whether vasoactive intestinal peptide (VIP) receptors are present in chronic periapical lesions and to determine whether differences in its expression are found according to the size of the lesions. METHODOLOGY: Twelve periapical lesions were obtained from teeth diagnosed with chronic apical periodontitis and indicated for endodontic surgery; they were classified according to the size of the lesion in two groups of six samples (lesion size greater or smaller than 5 mm), and then processed and labelled with (125)I-VIP. Binding sites were identified by (125)I-VIP and standard VIP competition assays. Mann-Whitney's test was used to establish statistically significant differences in the VIP receptor expression between groups. RESULTS: Vasoactive intestinal peptide receptor expression was found in all periapical lesion samples. There was a statistically significantly higher expression in periapical lesions <5 mm (P < 0.001). CONCLUSION: Vasoactive intestinal peptide receptors were expressed in chronic periapical lesions with levels inversely proportional to lesion size.

Substance P receptor expression in healthy and inflamed human pulp tissue.

AIM: To use radioreceptor analysis for comparing substance P (SP) receptor expression in human pulp tissue samples collected from teeth having a clinical diagnosis of acute irreversible pulpitis, healthy pulps and teeth with induced inflammation. METHODOLOGY: Five pulp samples were obtained from teeth having a clinical diagnosis of acute irreversible pulpitis. Another 10 pulp samples were obtained from healthy premolars where extraction was indicated for orthodontic purposes. In five of these premolars inflammation was induced prior to pulp collection. All of the samples were processed and labelled with 125I-SP. Binding sites were identified by 125I-SP and standard SP competition assays. Kruskal-Wallis and Mann-Whitney (post-hoc) tests were used to establish statistically significant differences between the groups. RESULTS: Substance P receptor expression was found in all human pulp tissue samples. Most receptors were found in the group of pulps from teeth having a clinical diagnosis of acute irreversible pulpitis, followed by the group of pulps having induced inflammation. The least number of receptors was expressed in the group of healthy pulps. Statistical analysis revealed significant differences between the group of healthy pulp and both inflamed pulp groups (P < 0.01). CONCLUSION: Substance P receptor expression in human pulp tissue is significantly increased during inflammatory phenomena such as acute irreversible pulpitis.

Effect site concentrations of propofol producing hypnosis in children and adults: comparison using the bispectral index.

BACKGROUND: No study has determined the concentration of propofol producing a degree of hypnosis compatible with anaesthesia in children. As a result, concentrations determined in adults are recommended for children. As this can result in an inadequate depth of anaesthesia, we determined the predicted effect site concentration (C(e)) of propofol necessary to obtain a bispectral index (BIS) of 50 in 50% (EC(e50)) of children and adults. METHODS: Twenty adults (aged 33-44 years) and 20 children (aged 3-11 years) undergoing surgery under general anaesthesia were studied. All were monitored with a BIS monitor, and a target controlled infusion of propofol aiming for a constant C(e) value was started. After 10 min, patients were evaluated using a sedation scale, and the last 5 min was used to determine the mean BIS for this C(e) value. The C(e) value of propofol was defined using the up-and-down method of Dixon and Massey. The first patient in each group received C(e)= 6 microg/ml; thereafter, it was modified in 0.5 microg/ml decrements/increments with positive or negative responses, respectively. A positive response was BIS < 50 and a negative response was BIS > or = 50. The EC(e50) value was compared using unpaired Student's t-test. The prediction probability (P(K)) was used to study the association between BIS and the sedation score. RESULTS: The mean EC(e50) (95% confidence interval) values were 3.75 microg/ml (2.97-4.75 microg/ml) in adults and 3.65 microg/ml (3.36-3.96 microg/ml) in children (not significant). All patients with BIS < 50 were unarousable with tactile stimulation. The P(K) value was 0.99 in both groups. CONCLUSIONS: The predicted C(e) value of propofol resulting in BIS = 50 was similar in adults and children aged 3-11 years. The predicted C(e) value of propofol producing hypnosis in adults also seems to be useful in this paediatric population.

[Pharmacodynamics of propofol in children and adults: comparison based on the auditory evoked potentials index]. / Farmacodinamia del propofol en niños y adultos: comparación usando el índice de potenciales evocados auditivos.

INTRODUCTION: The clinically useful concentrations of propofol to provide loss of consciousness in children have not been determined. Therefore, target-controlled infusion systems are used with parameters taken from results for adults. As a result, hypnosis can be inadequate in the pediatric population. We studied the dose-response relationship by comparing the predicted effect-site concentration (Ce) and the level of hypnosis measured by a monitor of depth of anesthesia based on auditory evoked potentials. MATERIAL AND METHODS: After injection of a submaximal bolus dose of propofol, the auditory evoked potential index was measured in 25 children (3-11 years old) and 25 adults (35-48 years old). We calculated the predicted Ce of propofol using the plasma effect-site equilibration rate constant (ke0) for each patient and the pharmacodynamic parameters of propofol for adults from the model of Schnider and for children from the models of Kataria and of the Paedfusor system. The relation of Ce to evoked potentials was analyzed with a sigmoid Emax model in the NONMEM program. RESULTS: The mean (SD) propofol doses in adults and children were 1.6 (0.1) mg x kg(-1) and 2.7 (0.3) mg x kg(-1), respectively. The Ce associated with auditory evoked potentials at 50% of the maximum effect (Ce50) for adults was 6.45 (0.59) microg/mL(-1), which was significantly higher than that estimated by either model for children (Kataria, 2.06 [0.24] microg/mL(-1); Paedfusor, 3.56 [0.22] microg/mL; P<0.001 between adults and children for both models). CONCLUSION: Children seem to be more sensitive to propofol than adults, suggesting that the higher dose requirements described for children would be attributable to pharmacokinetic differences between the 2 populations.

Farmacodinamia del propofol en niños y adultos: comparación usando el Índice de Potenciales Evocados Auditivos / Pharmacodynamics of propofol in children and adults: comparison based on the auditory evoked potentials index

INTRODUCCIÓN: Las concentraciones útiles de propofol para producir pérdida de consciencia no han sido determinadas en niños, por lo que se realiza infusión controlada por un ordenador (TCI) teniendo como parámetros los resultados obtenidos en adultos. Esto puede producir una hipnosis inadecuada en este segmento de la población. Comparamos la relación dosis-respuesta entre la concentración predicha en sitio efecto (Ce) y el nivel de hipnosis medido con un monitor de profundidad anestésica basado en los potenciales auditivos evocados (PAE). MATERIALES Y MÉTODOS: Tras administrar un bolo de propofol a dosis sub-máxima, el índice de hipnosis obtenido de los potenciales evocados (AAI) fue medido en 25 niños (3-11 años) y en 25 adultos (35-48 años). Con los valores de keO de cada paciente y con los parámetros farmacocinéticos de propofol del modelo de Schnider para los adultos y del modelo de Kataria y Paedfusor para los niños, estimamos las Ce de propofol durante el periodo de estudio para cada paciente. La relación Ce versus AAI se analizó con un modelo Emax sigmoideo con el programa NONMEM. RESULTADOS: Las dosis de propofol en adultos y niños fueron de 1,6 ± 0,1 mg kg-1 y 2,7 ± 0,3 mg kg-1 respectivamente. La Ce50 de propofol en adultos fue de 6,45 ± 0,59 µg/ml, significativamente más alta que la Ce50 estimada con el modelo Kataria (2,06 ± 0,24 µg/ml-1) y el modelo Paedfusor (3,56 ± 0,22 µg/ml-1) (p<0,001 entre adultos y niños con ambos modelos). CONCLUSIÓN: Los niños parecen ser más sensibles al propofol que los adultos. Esto sugiere que los mayores requerimientos descritos en niños serían atribuibles a diferencias farmacocinéticas con los adultos

INTRODUCTION: The clinically useful concentrations of propofol to provide loss of consciousness in children have not been determined. Therefore, target-controlled infusion systems are used with parameters taken from results for adults. As a result, hypnosis can be inadequate in the pediatric population. We studied the doseresponse relationship by comparing the predicted effectsite concentration (Ce) and the level of hypnosis measured by a monitor of depth of anesthesia based on auditory evoked potentials. MATERIAL AND METHODS: After injection of a submaximal bolus dose of propofol, the auditory evoked potential index was measured in 25 children (3-11 years old) and 25 adults (35-48 years old). We calculated the predicted Ce of propofol using the plasma effect-site equilibration rate constant (ke0) for each patient and the pharmacodynamic parameters of propofol for adults from the model of Schnider and for children from the models of Kataria and of the Paedfusor system. The relation of Ce to evoked potentials was analyzed with a sigmoid Emax model in the NONMEM program. RESULTS: The mean (SD) propofol doses in adults and children were 1.6 (0.1) mg·kg-1 and 2.7 (0.3) mg·kg-1, respectively. The Ce associated with auditory evoked potentials at 50% of the maximum effect (Ce50) for adults was 6.45 (0.59) µg/mL-1, which was significantly higher than that estimated by either model for children (Kataria, 2.06 [0.24] µg/mL-1; Paedfusor, 3.56 [0.22] µg/mL; P<0.001 between adults and children for both models). CONCLUSION: Children seem to be more sensitive to propofol than adults, suggesting that the higher dose requirements described for children would be attributable to pharmacokinetic differences between the 2 populations