Effects of melatonin on insulin signaling and inflammatory pathways of rats with apical periodontitis.

AIM: To verify the effects of melatonin supplementation on insulin sensitivity, plasma concentrations of inflammatory cytokines, insulin signalling and inflammatory pathways in the soleus (SM) and extensor digitorum longus (EDL) muscles of rats with apical periodontitis (AP). METHODOLOGY: Seventy-two Wistar rats were distributed into 4 groups: (a) control (C), (b) control supplemented with melatonin (M), (c) AP (AP), and (d) AP supplemented with melatonin (AP + M). AP was induced by pulp exposure of the maxillary and mandibular right first and second molars to the oral environment. After AP induction, oral supplementation with 5 mg kg-1 melatonin (diluted in drinking water) for 60 days was initiated. At the end of the treatment, the following were analysed: (1) plasma concentrations of insulin and inflammatory cytokines (TNF-α, IL-6, IL-1ß and IL-10) using ELISA kits; (2) glycaemia using enzymatic assay; (3) insulin resistance using homoeostasis model assessment of insulin resistance (HOMA-IR) index; and (4) phosphorylation status of pp185 tyrosine, Akt serine, IKKα/ß, and JNK in SM and EDL using Western blot. Analysis of variance of two or three factors was performed, followed by the Bonferroni test. P values < 0.05 were considered statistically significant. RESULTS: AP promoted insulin resistance, significantly increased (P < 0.05) plasma concentrations of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), significantly decreased (P < 0.05) the concentration of anti-inflammatory cytokine IL-10, impaired insulin signalling in SM, and increased IKKα/ß phosphorylation status in SM and EDL. Melatonin supplementation in rats with AP improved insulin sensitivity, significantly decreased (P < 0.05) TNF-α and IL-1ß, significantly increased (P < 0.05) IL-10 plasma concentrations, and changed the insulin signalling in soleus muscle and IKKα/ß phosphorylation status in SM and EDL muscles. CONCLUSIONS: Melatonin is a potent adjuvant treatment for improving apical periodontitis-associated changes in insulin sensitivity, insulin signalling and inflammatory pathways. In addition, the negative impact of AP on general health was also demonstrated.

Maternal apical periodontitis is associated with insulin resistance in adult offspring.

AIM: To investigate the plasma concentrations of glucose, insulin and tumour necrosis factor-α (TNF-α) of rats with maternal apical periodontitis (AP) and to explore the effect of maternal inflammation on the initial steps of insulin signalling and the inflammatory pathway in the gastrocnemius muscle (GM) and periepididymal white adipose tissue (pWAT) of adult offspring. METHODOLOGY: Fifteen female Wistar rats were distributed into a control group (CN), a group with 1 tooth with AP (1AP) and a group with 4 teeth with AP (4AP). Thirty days following induction of AP, female rats from all groups were mated with healthy male rats. When male offspring reached 75 days of age, plasma concentrations of glucose, insulin and TNF-α were quantified. Insulin resistance was evaluated by the homoeostasis model assessment of insulin resistance (HOMA-IR) index. Phosphorylation status of pp185 tyrosine, insulin receptor substrate 1 (IRS-1) serine, IκB kinase α/ß (IKKα/ß) and c-Jun N-terminal kinase (JNK) in the GM and pWAT were measured by Western blot. Analysis of variance was performed, followed by the Tukey's post hoc test. P values <0.05 were considered to be statistically significant. RESULTS: Maternal AP promoted insulin resistance, impaired the initial steps of insulin signalling, significantly increased plasma concentrations of insulin (P < 0.001) and TNF-α (P < 0.05), and enhanced IKKα/ß phosphorylation in the GM and pWAT (P < 0.05) of adult offspring. However, maternal AP did not affect fasting glycaemia and JNK phosphorylation in the GM and pWAT of adult offspring. CONCLUSIONS: Maternal AP was associated with insulin resistance in adult offspring through alterations in insulin signalling and inflammation pathways. The study provides information on the impact of maternal AP on the development of metabolic alterations such as insulin resistance in adult offspring and reinforces the importance of preventing maternal AP in order to maintain the general health of offspring.

Assessing age-related change in Japanese mental foramen opening direction using multidetector computed tomography.

OBJECTIVE: The purpose of this study was to investigate how the opening direction of the mental foramen (MF) changes with age in a Japanese population using multi-detector computed tomography (MDCT). METHODS: Post-mortem MDCT scans of 121 Japanese subjects (66 males and 55 females) were carried out where all subjects possessed at least twenty teeth, including molar teeth, in the upper and lower jaws. Two angles of the mental foramen opening were measured, namely the superior-inferior angle in the coronal plane and anterior-posterior angle in the transverse plane, on the CT reconstructed images. The associations between age and these two angles were evaluated using a multiple regression analysis. RESULTS: For male subjects, the relationship between the superior-inferior angle and age was a quadratic curve (p < 0.001). This angle increased until the subject reached their early 50s and then the angle decreased with age. In the transverse plane, there was a linear relation between the anterior-posterior angle and age (p=0.002).It was noted also that the angle decreased with age. By contrast, however, no significant associations between the two angles and age for either measurement were noted for female subjects. This study demonstrated that the opening direction of the mental foramen changes with age in Japanese male subjects. By contrast this change in the opening direction of the mental foramen was not demonstrated in Japanese female subjects. In male subjects, the opening direction moves superiorly until the individual reaches their early 50s, and then moves inferiorly with advancing age. It also shifts from a posterior to an anterior position with age. CONCLUSION: These observed change differ from the results of previous studies. The findings could be useful for forensic science as they demonstrate a change in the position of mental foramen in a sample of contemporaneous male Japanese subjects.

Evaluation of a personal identification method using the fusion function of CT images and dental radiographs.

OBJECTIVES: We applied the fusion function of dental analysis software to examine whether the anatomical relationships of tooth roots when compared between reconstructed post-mortem CT (PMCT) and dental radiographs can aid dental identification. METHODS: One PMCT image taken from a cadaver (43-year-old male; Cadaver 1) was compared with 64 digital dental radiographs of the left and right upper and lower molars from Cadaver 1 and 30 other cadavers. Five corresponding anatomical reference points were marked on each image. After adjusting the angle and magnification using the fusion function, the automatically calculated error in pixels was determined five times for each of four sites on the images. RESULTS: Comparison of the PMCT image with the dental radiographs from the other cadavers revealed obvious discrepancies in the anatomical positioning of the teeth. When t-tests were applied to the data from any of the four sites, the error in pixels was found to be significantly smaller (p < 0.001) between Cadaver 1 and the other cadaver images. The average error in pixels between the PMCT and dental radiographs was smaller in the lower jaw than in the upper jaw. CONCLUSIONS: This method uses corresponding reference points on two images to calculate the error between the regions that contain all points. This feature also makes it possible to compare images taken with different modalities. The demand for a dental identification method involving PMCT is likely to increase, and we expect that the accuracy of dental identification will improve by using radiological images.

Prevalence of deciduous tooth erosion in childhood.

OBJECTIVES: The objective of this study was to estimate the prevalence of deciduous tooth erosion and to identify possible associations with sex, age and toothbrushing frequency in children aged 4-6 years. METHODS: The sample was drawn from attendants (n = 7058) of 57 public preschools in a Brazilian city. Tooth wear index was used to evaluate erosion. Descriptive statistical analysis consisted of the calculation of the prevalence of dental erosion; chi-squared and Fisher's exact tests were performed to verify the association between dental erosion and sex, age and toothbrushing frequency. RESULTS: Two thousand and seven hundred and fifty-nine preschool students were examined. Deciduous tooth erosion was observed in 0.6% of children and its incidence did not differ between sexes. The highest prevalence was observed in children aged 6 years (58.3%) and the most affected sextants were the fourth (22.86%) and sixth (20.00%), indicating that lingual and occlusal tooth surfaces were most frequently involved. The degree of involvement was classified as incipient in 54.29% of children and moderate in 45.71%. The significance level was set at 5%. No association was found between erosion and sex, age or toothbrushing frequency. CONCLUSIONS: The prevalence of deciduous tooth erosion was low in Brazilian children, and this disorder is not considered a public health problem in this part of the population.

Investigating possible changes in protein structure during dendrimer-protein binding.

Building on our previous results that revealed a sized based mechanism for dendrimer/protein binding, the mechanism of complexation is further probed using CD spectroscopy; the results demonstrate that dendrimer/protein binding is not accompanied by changes in the protein's structure and that binding takes place on the interfacial area/active site entrance.

[Tissue distribution of cefminox in beagle dogs].

A new cephamycin antibiotic, cefminox (MT-141, CMNX), was intravenously infused into Beagle dogs at a dose of 40 mg/kg in order to study it's distribution to various tissues. The following results were obtained. The maximum serum concentration of CMNX observed at the end of the infusion period was 102.3 micrograms/ml, and then the concentration decreased. The biological half-life of CMNX in serum was 37.0 minutes. This half-life was similar to the results of previous studies with Beagle dogs and rabbits. The maximum concentrations in tissues and body fluids were highest in B-bile followed by kidney, urinary bladder, serum, liver, vagina, uterus, pericardiac fluid, trachea, ovary, lung, gallbladder, parotid gland, heart, tonsil, thymus, spleen, pancreas, aqueous humor and cerebrospinal fluid, in that order and not detected in brain. The maximum concentrations in gallbladder, B-bile, pericardiac fluid and cerebrospinal fluid were found at 1-2 hours after administration. In other tissues and body fluids, they were obtained at the end of the infusion period. The area under the tissue concentration curve (AUC) was highest in the urinary bladder followed by the kidney, vagina, liver, uterus, gallbladder, trachea, ovary and lung, in that order. These results suggest that CMNX is useful for various infectious diseases in these tissues. The pharmacokinetic parameter (K1i/K2i) derived from serum and tissue concentrations using the deconvolution method well correlated to maximum tissue concentrations.

A novel method to predict the elimination half-lives and the renal excretion mechanisms of cephalosporins.

A novel method was proposed to predict the elimination half-lives of cephalosporins from plasma protein binding (unbound fraction, f) and fraction of the dose excreted into urine (f*) on the basis of the following four assumptions. 1) The drug is only distributed to the extracellular fluid, 2) the bound fraction of the drug in plasma is independent of the plasma drug concentration, 3) the binding protein of the drug is albumin, 4) the unbound drug in plasma is excreted by the glomerular filtration and the contribution of active secretion and reabsorption is negligible. The VSS's and t1/2 beta's of MT-141, one of cephalosporins, in rabbits, dogs and healthy human subjects were well predicted, whereas in rats, the prediction of the both values was failed. The t1/2 beta's of various cephalosporins in healthy subjects were calculated from f and f*, in reasonably good agreement with the observed ones, except for some cephalosporins which have been reported to be secreted actively in the renal tubules. Thus, the comparison of the calculated t1/2 beta's with the observed ones makes it possible to presume the renal excretion mechanism. Moreover, this method will be applicable to other drugs which satisfy the above four assumptions.