Anti-Inflammatory Effects of Melatonin and 5-Methoxytryptophol on Lipopolysaccharide-Induced Acute Pulpitis in Rats.

AIM: The aim of this study was to investigate the possible therapeutic impacts of two pineal hormones, melatonin and 5-methoxytryptophol (5-MTX), in a rat model of acute pulpitis by analyzing biochemical and histopathological parameters. METHODS: This research was done using 32 male and female Wistar albino rats with weight between 200 and 250 g. The rats were randomly divided into four groups: a control group (rats without any treatment), acute pulpitis (AP) group, AP+melatonin group, and AP+5-MTX group. In the AP-induced groups, the crowns of the upper left incisors were removed horizontally. Lipopolysaccharide solution was applied to the exposed pulp tissue before the canal orifices were sealed with a temporary filling material. Melatonin (10 mg/kg) and 5-MTX (5 mg/kg) were administered intraperitoneally. The rats were sacrificed 24 hours after pulp injury, and trunk blood and pulp samples were collected. The concentrations of TNF-α, IL-1ß, MMP-1, and MMP-2 in sera and pulp samples were determined using ELISA assay kits. RESULTS: TNF-α, IL-1ß, MMP-1, and MMP-2 levels in the serum and pulp tissues were considerably higher in the AP group than the control group (p < 0.01-0.001). In the AP+melatonin and AP+5-MTX groups, TNF-α, IL-1ß, MMP-1, and MMP-2 levels in the serum and pulp tissues were significantly lower than in the AP group (p < 0.05-0.001). CONCLUSIONS: Both melatonin and 5-MTX provided protective effects on acute pulpitis, which indicates they may be promising as a therapeutic strategy for oral disease.

A Prospective Clinical Pilot Study on the Level of Matrix Metalloproteinase-9 in Dental Pulpal Blood as a Marker for the State of Inflammation in the Pulp Tissue.

INTRODUCTION: Differentiation between reversible pulpitis (savable pulp) and irreversible inflammation of the pulp tissue (nonsavable pulp) based only on clinical and radiographic diagnoses has proven to be difficult. Pulp exposure allows for the collection of pulpal blood to quantitatively determine the level of inflammation markers or proteolytic enzymes, even with small samples. Pulpitis is associated with the invasion of neutrophil granulocytes and their release of matrix metalloproteinase-9 (MMP-9). METHODS: Forty-four patients (aged 18-74 years, mean = 35 years), each with 1 tooth with carious pulp exposure presenting with different stages of pulpitis, were included in this prospective, 2-center clinical study; 26 patients presented with irreversible pulpitis (groups 3 and 4), 10 with reversible pulpitis (group 2), and 8 with completely asymptomatic teeth with deep carious lesions (group 1). Six of the 26 patients with teeth diagnosed with irreversible pulpitis had not taken any nonsteroidal anti-inflammatory drugs and were evaluated as a separate group (group 4). Partial pulpotomy and blood sample collection from the pulp chamber were performed. The total levels of MMP-9 and tissue inhibitor of metalloproteinase-1 were assessed by fluorometric and colorimetric enzyme-linked immunosorbent assays, respectively. The Mann-Whitney U test and Spearman rank correlations were used to compare the MMP-9 levels with different stages of pulpal inflammation; significance was set at .05. RESULTS: The MMP-9 levels in the asymptomatic teeth (group 1) were significantly different from those in the teeth with reversible pulpitis (group 2, P = .006) or irreversible pulpitis (group 4, P < .001). A statistically significant difference was also observed between the MMP-9 levels in group 1 and group 3 (P < .001) in which the patients had taken nonsteroidal anti-inflammatory drugs. CONCLUSIONS: These findings indicate that the MMP-9 levels in pulpal blood samples could be a useful ancillary diagnostic tool for distinguishing different stages of pulp tissue inflammation.

Cytokines as diagnostic markers of pulpal inflammation.

AIM: To measure and compare the levels of the cytokines IL-2, IL-6, IL-8, IL-10, TNF-α and IFN-γ in pulpal blood from irreversible pulpitis, asymptomatic caries exposure and normal pulps. METHODOLOGY: Blood was obtained from pulp exposure sites using cotton pellets. Twenty-five samples were obtained from normal teeth, 40 from asymptomatic caries-exposed pulps and 43 from irreversible pulpitis teeth. Cytokine levels were determined by high-sensitivity ELISA. Data were statistically analysed using Kruskal-Wallis and Mann-Whitney U-tests. RESULTS: Significantly higher levels (P < 0.05) of IL-6, IL-8, IL-10, TNF-α and IFN-γ were detected in caries-exposed pulps and irreversible pulpitis as compared to normal teeth. IL-2 and IL-10 levels were significantly higher (P < 0.05) in caries-exposed pulps as compared to irreversible pulpitis, whilst IL-8 was significantly higher (P < 0.001) in irreversible pulpitis as compared to caries-exposed teeth. Most interestingly, IL-6/IL-10 and IL-8/IL-10 ratios were significantly higher (P < 0.001) in irreversible pulpitis compared with both caries-exposed and normal teeth. CONCLUSION: Levels of IL-8 and the ratios of IL-6/IL-10 and IL-8/IL-10 have the potential to be indicators of pulpal inflammation in caries exposure cases. Cytokine estimation in pulpal blood may help in the diagnosis of pulpal inflammation.

[Antibiotic therapy in odontogenic infections in children and adolescents: pharmacokinetic/pharmacodynamic analysis]. / Utilización de antimicrobianos en las infecciones odontogénicas en niños y adolescentes: análisis farmacocinético/farmacodinámico (PK/PD).

INTRODUCTION: The objective of this study was to evaluate the efficacy of the most commonly used antimicrobial treatments in odontogenic infections in children and adolescents on the basis of pharmacokinetic/ pharmacodynamic (PK/PD) criteria. METHODS: Unbound drug plasma concentration-time curves were simulated with mean population pharmacokinetic parameters of amoxicillin, co-amoxiclav, cefuroxime axetil, spiramycin, clindamycin, azithromycin, and metronidazole. For drugs showing time-dependent antibacterial killing, the time above MIC90 of the pathogens studied was calculated (T>MIC). For drugs with concentration-dependent bactericidal activity, the area under the concentration-time curve (AUC)/MIC90 ratio was calculated. RESULTS: Adequate efficacy indexes (T>MIC>40%) against all the microorganisms examined with the exception of Veillonella spp. were obtained with co-amoxiclav (80 mg/kg/day). Clindamycin (40 mg/kg/day) obtained adequate PK/PD indexes except for Lactobacillus, Actinobacillus actinomycetemcomitans, penicillin-resistant Peptostreptococcus, and Eikenella corrodens. High-dose amoxicillin yielded unsatisfactory results against many bacterial species. Azithromycin and metronidazole showed inadequate efficacy indexes against the majority of pathogens studied (AUC/MIC90<25). CONCLUSION: When antibiotic therapy is needed for odontogenic infections in children and adolescents, the most active empirical therapeutic choice is co-amoxiclav with high doses of amoxicillin. Clindamycin can be used as an alternative option. These results should be confirmed in clinical trials, in which the PK/PD approach could be useful for the design and assessment of results.

Nitric oxide levels in serum of patients with symptomatic irreversible pulpitis.

Nitric oxide (NO) affects both pain and inflammation in human tissues. Pharmacotherapy that decreases NO concentrations may have utility in treating inflammatory painful conditions. To determine the types of disorders in which such an approach should be studied, changes in NO serum levels before and after the painful inflammatory condition resolves would be helpful. This study compared the pre-treatment and post-treatment serum nitric oxide (NO) concentrations in irreversible pulpitis (inflammatory toothache). Thirty-two patients (16 males, 16 females) with irreversible pulpitis were included in this study. Before treatment, patients had severe symptoms of inflammation, but at the end of treatment no symptoms of inflammation were observed. NO concentrations were measured in serum of patients with irreversible pulpitis, before and after treatment. Differences in serum NO concentrations were not statistically significantly different before and after treatment.

Prostaglandin E2 and treatment outcome in pulp therapy of primary molars with carious exposures.

OBJECTIVES: Prostaglandin E2 (PGE2) has been suggested as an indicator of irreversible pulpitis in permanent teeth [1]. There is scant information on the role of chemical mediators in primary molar pulp inflammation. The aim of this preliminary study was to investigate the levels of PGE2 in blood harvested from root pulp stumps following coronal pulp amputation in vital primary molar teeth with carious exposures. METHODS: Seventy-nine cariously exposed primary molars underwent treatment by one of two vital pulp therapy techniques. Blood was harvested from 38 teeth and volume and concentration of PGE2 ([PGE2]) determined [2]. Treatment outcome was assessed from both clinical and radiographic evidence. RESULTS: PGE2 was detected in all samples, with a wide concentration range (1-2641 ng/mL). The distribution was skewed, requiring log transformation. The difference in the mean (log) [PGE2] for radiological success (3.12, SD 1.60 and failure (4.62, SD 1.80) was significant, t = 2.05, P = 0.047. The difference in the mean (log) [PGE2] for clinical success (3.24, SD 1.65) and failure (5.44, SD 1.43 was near-significant, t = 1.84, P = 0.074. CONCLUSION: [PGE2] correlated positively with radiological outcome following vital pulp therapy.

Quantitative analysis of immunoglobulins and inflammatory factors in human pulpal blood from exposed pulps.

The levels of immunoglobulins (IgG, IgA, and IgM) and inflammatory factors (elastase, prostaglandin E2, interleukin-1 alpha, interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) in the blood of human dental pulp were quantified, using enzyme-linked immunosorbent assays. The pulpal blood samples were obtained with nylon fiber pellets from normal and inflamed dental pulp at pulp sites exposed on pulpectomy. Statistically significant differences between normal and inflamed pulp were found in the levels of IgG (p < 0.01), IgA (p < 0.05), IgM (p < 0.01), elastase (p < 0.05), and prostaglandin E2 (p < 0.01). These findings indicate that these factors play an important role in the pathogenesis of pulpal disease, and the sampling methods used in this study are useful for examination of pulpal inflammation.

Comparison of human polymorphonuclear neutrophil elastase, polymorphonuclear neutrophil cathepsin-G, and alpha 2-macroglobulin levels in healthy and inflamed dental pulps.

Polymorphonuclear neutrophils (PMNs) are found in dental pulp secondary to carious exposures, periodontal disease, or trauma. Lysosomal degranulation of these cells liberates cellular proteases, including elastase (PMN-E) and cathepsin-G (PMN-CG), which produce connective tissue degradation. However, nonspecific pulpal tissue destruction can be modified by a naturally occurring serum protease inhibitor alpha 2-macroglobulin (A2-M). This study relates the concentrations of human PMN-E, PMN-CG, and A2-M in healthy and inflamed pulpal samples. Evaluation of 21 specimens yielded statistically significant differences between healthy and moderate to severely inflamed pulps for all groups (p < 0.05). No significant correlation was detected among human PMN-E, PMN-CG, and A2-M in the healthy tissues (P > 0.05). However, in the moderate to severely inflamed pulps, there was a significant correlation between PMN-CG and A2-M (p < 0.05).

[Study on the diagnosis of the deciduous tooth pulpitis by the blood picture in the dental pulp].

The purpose of this study was to investigate the method of diagnosis of deciduous tooth pulpitis to make sure of the extent of the inflammation for more appropriate pulp therapy. The subjects were 100 decayed deciduous teeth of the 81 normal healthy children aged from 2y9m to 11y2m, which justified the vital pulp amputation therapy according to Nagasaka's deciduous tooth pulpitis diagnosis criteria. The blood picture was compared with the histological structure of the coronal pulp and then observed after treatment. The diagnosis of the deciduous tooth pulpitis was considered by the blood picture in the dental pulp. The results were as follows. 1. As to the blood picture in the deciduous dental pulp, it was suggested that the lymphocyte ratio was able to be taken for the discrimination of the deciduous tooth pulpitis, because ratio of lymphocyte in the coronal pulp was higher than its normal values in the peripheral blood picture regardless of the age. 2. As to the histological structure of the removed coronal pulp, the inflammatory degree was divided into 4 types; (-) no evidence of inflammation, (+) slightly confined infiltration of the inflammatory cells, (++) slightly or moderately diffused infiltration, ( ) severely diffused infiltration, when the numbers of the case at each degree type were (-) 0, (+) 37, (++) 47 and ( ) 16 cases. 3. As to the ratio of the lymphocyte ratio over 60% against all at each degree type, (+) 86.5% and (++) 61.7% were much higher than ( ) 0%. 4. The ratio of cases in which it was difficult to control bleeding at ratios of the coronal pulp amputations were type (+) 32.4% and (++) 25.5% in type, however, type ( ) showed high rate (62.5%). 5. As a result of the clinical and X-ray examination after vital pulp amputation therapy, the number of poor case was 12 of 42 cases (28.6%) in type (+) (++) and 4 of 4 cases (100%) in type ( ). 6. This result suggests that the vital pulp amputation therapy is not adequate when it is hard to control bleeding and the lymphocyte ratio of blood picture in the coronal pulp shows under 57%.

Immunoglobulin and haematocrit values of dental pulp showing hyperaemia and acute serious pulpitis.

In this study, we examined how the pulpal immune systems differ in children who suffer from hyperaemia and acute serous pulpitis. The Radial Immune Diffusion (RID) method was used to measure the IgA, IgG and IgM levels in pulpal blood in hyperaemia and acute serous pulpitis cases. The patient's own peripheral blood was used as the control group. The peripheral blood was taken with a capillary tube from the finger tip. The immunoglobulins and the Htc values of the blood were measured by the radial immune diffusion method. In our research, the immunoglobulin and hematocrit values of the blood (pulpal and peripheral) of 39 patients between the ages 6 to 13 years were measured. No significant difference was found between the IgA, IgG and IgM levels of pulpal and peripheral blood in hyperaemia and acute serous pulpitis cases. In the same patients, a significant difference was noted between the Htc values of the pulpal and peripheral blood.