Pressure pain threshold of masticatory muscles in children and adolescents with and without intellectual disability: a pilot study.

PURPOSE: Pain is considered a stressful experience, related to real or possible tissue damage with emotional, sensory, social and cognitive components. The aim of the study was to evaluate and compare, using a digital algometer, the pressure pain threshold of temporal and masseter muscles of children and adolescents with and without intellectual disability. METHODS: A cross-sectional study was conducted. Data regarding gender and age were collected from the caregiver of children and adolescents with and without intellectual disability. The evaluations followed this sequence: pressure pain threshold of the masseter and temporal muscles, evaluation of pain on touch using the visual analog scale and signs and symptoms of Temporomandibular disorder. The χ2 test, the Kolgomorov-Smirnov test, Student t test and Mann-Whitney test were performed. The significance level was set at 5%. RESULTS: Two homogeneous groups by gender (P = 0.258) and age (P = 0.727) were evaluated, of which 25 children and adolescents presented intellectual disability and another 25 did not have intellectual disability. No significant difference was observed between groups on the pressure pain threshold of the masseter and temporal muscles, nor pressure average or exam time (P > 0.05). Regarding Temporomandibular dysfunction, no difference in signs or symptoms frequency was found (P > 0.05). However, the range of maximum mouth opening was smaller in the intellectual disability group (P = 0.006). CONCLUSION: Children and adolescents with intellectual disability and preserved basic functionalities do not present alterations in pain perception when evaluated with computerized pressure algometer and visual analog scale. They present similar threshold of pain to pressure as those reported by normative children and adolescents. These results emphasize the importance to treat these children and adolescents with intellectual disability with respect to their pain threshold.

Effects of treatments for drooling on caries risk in children and adolescents with cerebral palsy.

BACKGROUND: Neuromuscular impairment makes individuals with cerebral palsy (CP) more prone to drooling. Among the treatment options, there are procedures that interfere with saliva production. It is imperative to evaluate the effect of the different modalities since the reduction in salivary flow rate/production may exacerbate the risk of dental caries. MATERIAL AND METHODS: The aim of this study was to compare the effects of different treatments for drooling on caries risk and salivary parameters in children and adolescents with CP. STUDY DESIGN: A total of 142 children and adolescents with CP, aged 6 to 18 years, were assigned to groups based on the different treatments they had received for drooling: G1-anticholinergic drugs (n = 18), G2-botulinum toxin injection (n = 16), G3-salivary glands surgery (n = 16), G4-no treatment (n = 42), and G5-non-drooling subjects (n = 50). All participants were evaluated on the Simplified Oral Hygiene Index, and for the prevalence of dental caries (decayed, missing, and filled teeth index and white spot lesions). Unstimulated whole saliva was collected, and salivary flow rate and osmolality were measured. Chi-square, ANOVA and Poisson regression were calculated. Prevalence ratios and their respective 95 % confidence intervals were obtained. The significance level was fixed at 5%. RESULTS: No differences were found in the decayed, missing, and filled teeth index (p = 0.128) and Simplified Oral Hygiene Index (p = 0.674) among the different groups. G3 presented significantly higher percentages of WSL (p < 0.001), lower values of salivary flow rate (p < 0.001), and higher values of osmolality (p < 0.001). The white spot lesion prevalence ratio was higher only for G3 (Prevalence ratio = 14.36; IC 95% = 4.64-44.40; p < 0.001). CONCLUSIONS: Children and adolescents with CP who had received surgical treatment for drooling exhibited higher number of white spot lesions because of the reduced salivary flow rate and higher salivary osmolality.

DuOx2 Promoter Regulation by Hormones, Transcriptional Factors and the Coactivator TAZ.

The production of H2O2, which is essential to thyroid hormone synthesis, involves two NADPH oxidases: dual oxidases 1 and 2 (DuOx1 and DuOx2). A functional study with human DuOx genes and their 5'-flanking regions showed that DuOx1 and -2 promoters are different from thyroid-specific gene promoters. Furthermore, their transcriptional activities are not restricted to thyroid cells. While regulation of Tg (thyroglobulin) and TPO (thyroperoxidase) expression have been extensively studied, DuOx2 promoter regulation by hormones and transcriptional factors need to be more explored. Herein we investigated the role of TSH, insulin and insulin-like growth factor 1 (IGF-1), as well as the cAMP effect on DuOx2 promoter (ptx41) activity in transfected rat thyroid cell lines (PCCL3). We also assessed DuOx2 promoter activity in the presence of transcriptional factors crucial to thyroid development such as TTF-1 (thyroid transcription factor 1), PAX8, CREB, DREAM, Nkx2.5 and the coactivator TAZ in HeLa and HEK 293T-transfected cells. Our results show that TSH and forskolin, which increase cAMP in thyroid cells, stimulated DuOx2 promoter activity. IGF-1 led to pronounced stimulation, while insulin induction was not statistically different from DuOx2 promoter basal activity. All transcriptional factors selected for this work and coactivator TAZ, except DREAM, stimulated DuOx2 promoter activity. Moreover, Nkx2.5 and TAZ synergistically increased DuOx2 promoter activity. In conclusion, we show that DuOx2 expression is regulated by hormones and transcription factors involved in thyroid organogenesis and carcinogenesis, reinforcing the importance of the control of H2O2 generation in the thyroid.

MCT8 is Downregulated by Short Time Iodine Overload in the Thyroid Gland of Rats.

Wolff-Chaikoff effect is characterized by the blockade of thyroid hormone synthesis and secretion due to iodine overload. However, the regulation of monocarboxylate transporter 8 during Wolff-Chaikoff effect and its possible role in the rapid reduction of T4 secretion by the thyroid gland remains unclear. Patients with monocarboxylate transporter 8 gene loss-of-function mutations and monocarboxylate transporter 8 knockout mice were shown to have decreased serum T4 levels, indicating that monocarboxylate transporter 8 could be involved in the secretion of thyroid hormones from the thyroid gland. Herein, we aimed to evaluate the regulation of monocarboxylate transporter 8 during the Wolff-Chaikoff effect and the escape from iodine overload, besides the importance of iodine organification for this regulation. Monocarboxylate transporter 8 mRNA and protein levels significantly decreased after 1 day of NaI administration to rats, together with decreased serum T4; while no alteration was observed in LAT2 expression. Moreover, both monocarboxylate transporter 8 expression and serum T4 was restored after 6 days of NaI. The inhibition of thyroperoxidase activity by methimazole prevented the inhibitory effect of NaI on thyroid monocarboxylate transporter 8 expression, suggesting that an active thyroperoxidase is necessary for MCT8 downregulation by iodine overload, similarly to other thyroid markers, such as sodium iodide symporter. Therefore, we conclude that thyroid monocarboxylate transporter 8 expression is downregulated during iodine overload and that the normalization of its expression parallels the escape phenomenon. These data suggest a possible role for monocarboxylate transporter 8 in the changes of thyroid hormones secretion during the Wolff-Chaikoff effect and escape.

Decreased serum T3 after an exercise session is independent of glucocorticoid peak.

Physical exercise increases serum glucocorticoids, which is believed to be involved in the fall of T3 after high intensity exercise. The objective was to evaluate whether a physical exercise session alters the thyroid economy and adrenal axis in humans, and the possible role of corticosteroids in thyroid function disturbance. Active but not athlete subjects were enrolled in an open field competition and cortisol, TSH, T3, and T4 were measured before and after the race. To give new insights into the mechanisms underlying the changes in thyroid economy after exercise, we used a rat model to evaluate the impact of blocking corticosterone synthesis during treadmill exercise by metyrapone administration. Cortisol levels increased 1.5-fold (from 28.2±3.8 to 42.2±2.2 µg/dl; p<0.05), while serum T3 decreased by 13% (from 115±5 to 99±5 µg/dl; p<0.05) 6 h after the race in humans. Also, in rats, glucocorticoid increased by 2-fold while T3 decreased 15% after exercise session (p<0.05). However, the complete blockage of corticosterone peak did not impair serum T3 decrease observed in rats submitted to exercise. Interestingly, the lack of corticosterone peak led not only to lower serum T3, but also to decreased serum T4, indicating that corticosterone might be fundamental for the maintenance of serum thyroid hormone levels after high intensity exercise. Although cortisol increases and T3 decreases after high intensity exercise in both humans and rats, it does not seem to be a cause-effect response since pharmacological blockage of corticosterone peak does not modulate T3 response.

Tissue-specific deiodinase regulation during food restriction and low replacement dose of leptin in rats.

The relationship between thyroid function and leptin has been extensively studied; however, the mechanisms underlying the changes in thyroid hormone economy that occur during caloric deprivation remain elusive. Our goal was to evaluate the thyroid function of rats submitted to 40% food restriction after chronic leptin replacement. Caloric restriction for 25 days led to significantly reduced serum leptin, thyroid-stimulating hormone (TSH), thyroxine (T(4)), and triiodothyronine (T(3)) and increased serum corticosterone, while liver, kidney, and thyroid type I deiodinase (D1) and brown adipose tissue (BAT) type II deiodinase (D2) activities were decreased and hypothalamic D2 was significantly increased. Interestingly, thyroid iodide uptake was unchanged by caloric restriction, but thyroperoxidase (TPO) activity was significantly reduced. Leptin replacement for the last 10 days of caloric restriction normalized serum leptin and TSH levels, but serum T(4) and T(3) levels and thyroid D1 and TPO activities were not reestablished. Also, a negative effect of leptin administration on Na(+)-I(-) symporter function was detected. Liver and kidney D1 and hypothalamic and BAT D2 were normalized by leptin, while pituitary D2 was significantly decreased. In conclusion, a tissue-specific modulation of deiodinases might be implicated in the normalization of thyroid function during leptin replacement in food-restricted rats. Although leptin restores the hypothalamus-pituitary axis during food restriction, it exerts a direct negative effect on the thyroid gland; thus normalization of serum thyroid hormones might depend on changes in deiodinase activities and the long-term thyroid stimulation by TSH to counterbalance the direct negative effects of leptin on the thyroid gland.

Profile of serum IL-1beta and IL-10 shortly after ovariectomy and estradiol replacement in rats.

Ovariectomy leads to progressive and significant increases in body weight gain and osteoporosis and is related to changes in serum and tissue cytokine profiles, such as observed in other models of overweight. We aimed to evaluate serum interleukin-1beta and interleukin-10 shortly after ovariectomy, before the establishment of overweight in rats. Female Wistar rats were submitted to ovariectomy, ovariectomy and estradiol replacement, or sham operation and compared with intact controls. Rats were killed 3, 6, 9, or 13 d after ovariectomy. Body mass and retroperitoneal fats were significant higher only 13 d after ovariectomy, and estradiol replacement to ovariectomized rats impaired both body mass and retroperitoneal fat gain. Shortly after ovariectomy (at 3 d) serum interleukin-1beta levels significantly increased in ovariectomized rats, treated or not with estradiol, while serum interleukin-10 levels increased only 9 d after ovariectomy. Our results suggest the existence of an important interplay between the immune system and ovarian function. This interplay occurs regardless of significant changes in adipose tissue compartment, as ovarian excision leads to short-term changes in the pattern of interleukin-1beta and interleukin-10 cytokine production that precede body weight gain and are not reverted by estradiol replacement.

Tryptophan consumption and indoleamines production by peritoneal cavity macrophages.

Melatonin has been shown to regulate several immune functions, and some authors showed that leukocytes are also able to produce the indolamine. In fact, it seems to take part in some immunoregulatory axis, including that related to interferon (IFN) production. So, we evaluated the rate of tryptophan consumption and melatonin and serotonin production in peritoneal cavity-isolated macrophages and the effect of IFN-alpha and -gamma, lipopolysaccharide (LPS), and phorbol myristate acetate (PMA) on such parameters. Our results indicate that macrophages obtained from the peritoneal cavity of normal rats when incubated with tryptophan show an increase in arylalkylamine N-acetyltransferase activity that corresponds to an increased melatonin production, as determined in the incubation medium. This process is regulated by IFN-alpha and -gamma, PMA, LPS, and the serum from tumor-bearing rats, opening the possibility of speculation about different immunoregulatory loops acting through the balance of melatonin/serotonin production by such cells.

Inhibition of thyroid type 1 deiodinase activity by flavonoids.

Some dietary flavonoids inhibit thyroperoxidase and hepatic deiodinase activity, indicating that these compounds could be classified as anti-thyroid agents. In this study, we evaluated the in vitro effect of various flavonoids on thyroid type 1 iodothyronine deiodinase activity (D1). D1 activity was measured in murine thyroid microsome fractions by the release of 125I from 125I-reverse T3. D1 activity was significantly inhibited by all the flavonoids tested; however, the inhibitory potencies on thyroid D1 activity differed greatly among them. A 50% inhibition of D1 activity (IC(50)) was obtained at 11 microM baicalein, 13 microM quercetin, 17 microM catechin, 55 microM morin, 68 microM rutin, 70 microM fisetin, 72 microM kaempferol and 77 microM biochanin A. Our data reinforce the concept that dietary flavonoids might behave as antithyroid agents, and possibly their chronic consumption could alter thyroid function.

Thyroid peroxidase activity is inhibited by amino acids

Normal in vitro thyroid peroxidase (TPO) iodide oxidation activity was completely inhibited by a hydrolyzed TPO preparation (0.15 mg/ml) or hydrolyzed bovine serum albumin (BSA, 0.2 mg/ml). A pancreatic hydrolysate of casein (trypticase peptone, 0.1 mg/ml) and some amino acids (cysteine, tryptophan and methionine, 50 µM each) also inhibited the TPO iodide oxidation reaction completely, whereas casamino acids (0.1 mg/ml), and tyrosine, phenylalanine and histidine (50 µM each) inhibited the TPO reaction by 54 per cent or less. A pancreatic digest of gelatin (0.1 mg/ml) or any other amino acid (50 µM) tested did not significantly decrease TPO activity. The amino acids that impair iodide oxidation also inhibit the TPO albumin iodination activity. The inhibitory amino acids contain side chains with either sulfur atoms (cysteine and methionine) or aromatic rings (tyrosine, tryptophan, histidine and phenylalanine). Among the amino acids tested, only cysteine affected the TPO guaiacol oxidation reaction, producing a transient inhibition at 25 or 50 µM. The iodide oxidation inhibitory activity of cysteine, methionine and tryptophan was reversed by increasing iodide concentrations from 12 to 18 mM, while no such effect was observed when the cofactor (H2O2) concentration was increased. The inhibitory substances might interfere with the enzyme activity by competing with its normal substrates for their binding sites, binding to the free substrates or reducing their oxidized form.