AMP-activated protein kinase (AMPK) is activated by the depletion in cellular energy levels and allows adaptive changes in cell metabolism and cell survival. Recently, our group described that AMPK plays an important role in the regulation of iodide and glucose uptake in thyroid cells. However, AMPK signaling pathway in human thyroid carcinomas has not been investigated so far. Objective: To evaluate the expression and activity of AMPK in papillary thyroid carcinomas. Methods: We examined total and phosphorylated AMPK (tAMPK and pAMPK) and phosphorylated acetyl-CoA-carboxylase (pACC) expressions through imunohistochemistry, using a tissue microarray block composed of 73 papillary thyroid carcinomas (PAP CA) or microcarcinomas (PAP MCA) and six adenoma (AD) samples from patients followed at the Federal University Hospital. The expression levels were compared with the non-neoplastic tissues from the same patient. Two different pathologists analyzed the samples and attributed scores of staining intensity and the proportion of stained cells. A total index was obtained by multiplying the values of intensity and the proportion of stained cells (INTxPROP). Results: tAMPK, pAMPK, and pACC showed a predominant cytoplasmic staining in papillary carcinomas, adenomas, and non-neoplastic thyroid tissues. However, the intensity and the proportion of stained cells were higher in carcinomas, so that a significant increase was found in the INTxPROP score both in PAP CA and PAP MCA, when compared with their respective controls. Conclusion: Our results show unequivocally that AMPK pathway is highly activated in papillary thyroid carcinomas; however, more studies are necessary to understand the pathophysiological significance of AMPK activation in thyroid carcinogenesis.

Evidence suggests that diabetic patients are more significantly affected by problems of endodontic origin. This study sought to radiographically and histologically examine the development of periradicular inflammation in control and in diabetic rats after induction of pulpal infection. The pulps of the mandibular first molars of normal and streptozotocin-induced diabetic rats were exposed and left in contact with their oral cavities for 21 and 40 days. Afterwards, the animals were sacrificed, the mandibles were surgically removed, fixed in formalin and then radiographed in a standardized position. The radiographic images of the periradicular lesions were scanned and computerized images were evaluated for the total area of the lesions using a specific software. Representative specimens were also prepared for histopathological analysis. Radiographic analysis revealed that diabetic rats presented significantly larger periradicular lesions when compared with control rats, regardless of the experimental period (p<0.05). Histopathological examination of representative specimens revealed larger periradicular lesions and more severe inflammatory exudate in the group of diabetic rats when compared with the control group. Data from the present study indicated that diabetic rats can be more prone to develop large periradicular lesions, possibly due to reduction in the defense ability against microbial pathogens.

Direct intravital microscopic examinations of nailfold capillaries were made in three groups of subjects: 15 healthy volunteers (C) and 11 patients, six with hypothyroidism (h) and five with hyperthyroidism (H). The groups h and H were examined twice, before the onset of treatment and when they returned to euthyroidism. Capillary blood flow velocity (CBFV) was measured during rest and after release of 60-second arterial occlusion. To assess autoregulatory capacity the authors determined peak CBFV postocclusion and time to reach it in single capillaries. In patients with hypothyroidism, before the onset of the treatment, the mean resting and the mean peak CBFV were significantly lower (resting CBFV-group C: 0.93+/-0.11 mm/s (mean+/-SE); group h: 0.33+/-0.09 mm/s; and mean peak CBFV-group C: 1.49+/-0.14 mm/s; group h: 0.79+/-0.19 mm/s). The time to reach mean peak CBFV postocclusion was significantly prolonged (group C: 8.9+/-0.65 s and group h: 19.2+/-2.0 s) compared with the group of healthy volunteers. When these patients achieved euthyroidism, all the studied parameters returned to control levels. In patients with hyperthyroidism only minor changes in CBFV could be detected. In patients with hypothyroidism, the skin microvascular autoregulatory mechanisms are disturbed. The impairments of the reactive hyperemia response could be correlated with the control of the disease (thyroid state).

The objective of the present study was to examine whether hypothyroidism affects the reproductive system of adult female rats by evaluating ovarian morphology, uterus weight and the changes in serum and pituitary concentrations of prolactin and gonadotropins. Three-monthold female rats were divided into three groups: control (N = 10), hypothyroid (N = 10), treated with 0.05% 6-propyl-2-thiouracil (PTU) in drinking water for 60 days, and T 4 -treated group (N = 10), receiving daily sc injections of L-thyroxine (0.8 µg/100 g body weight) during the last 10 days of the experiment. At the end of 50 days of hypothyroidism no hypothyroid animal showed a regular cycle, while 71% of controls as well as the T 4 -treated rats showed regular cycles. Corpora lutea, growing follicles and mature Graafian follicles were found in all ovaries studied. The corpora lutea were smaller in both the hypothyroid and T 4 -replaced rats. Graafian follicles were found in 72% of controls and only in 34% of hypothyroid and 43% of T 4 -treated animals. Serum LH, FSH, progesterone and estradiol concentrations did not differ among the three groups. Serum prolactin concentration and the pituitary content of the three hormones studied were higher in the hypothyroid animals compared to control. T 4 treatment restored serum prolactin concentration to the level found in controls, but only partially normalized the pituitary content of gonadotropins and prolactin. In conclusion, the morphological changes caused by hypothyroidism can be a consequence of higher prolactin production that can block the secretion and action of gonadotropins, being the main cause of the changes observed.

We determined the hormonal, metabolic and ultrasonographic pattern of adolescents with menstrual irregularity since menarche but without clinical signs of hyperandrogenism with the aim of evaluating whether this condition represents an early stage of polycystic ovary syndrome (PCOS). These adolescents were divided in two groups: 13 adolescents with irregular cycles (IC) within the first 3 postmenarchal years (IC < or = 3) and 15 adolescents having persistent irregular cycles for more than three postmenarchal years (IC > 3). These adolescents were compared with 15 adolescents with PCOS and 18 normal adolescents. The values of free testosterone, free androgen index, luteinizing hormone (LH) and LH/follicle-stimulating hormone (FSH) ratio were similar in IC < or = 3, IC > 3 and PCOS, and higher than in the normal group (p < 0.005). The total testosterone and androstenedione levels were higher and sex hormone-binding globulin (SHBG) lower in PCOS only when compared with the normal group (p < 0.05). The ovarian volume was similar in IC < or = 3, IC > 3 and PCOS, and higher than in the normal group (p < 0.005). A higher incidence of polycystic structure was found in IC < or = 3, IC > 3 and PCOS, whereas normal structure was more common in normal adolescents (p < 0.0005). There were no significant differences in glucose and insulin parameters between groups. These results indicate that menstrual irregularity within the first postmenarchal years can be an early clinical sign of PCOS.