Hypothalamic orexin neurons are known to regulate sleep/wake stability, feeding behavior, emotions, autonomic nerve activity, and whole-body energy metabolism. In addition, emerging evidence indicates that orexin contributes to central regulation of glucose homeostasis. Intriguingly, central administration of orexin is reported to cause blood glucose-elevating effect or blood glucose-lowering effect in rodents, depending on the experimental conditions. Here we reviewed the recent reports regarding the mode and mechanism of actions of orexin on these two opposing effects, and discuss the functional significance for the maintenance of glucose homeostasis. The fact that orexin exhibits biphasic effects on autonomic nerve activity and lipolysis suggests that orexin dually regulates the glucose appearance. In fact, orexin neurons are activated not only depending on the demand for glucose but also according to a circadian rhythm in the suprachiasmatic nucleus. The excited orexin neurons appear to alter the sympathetic or parasympathetic outflow to the periphery, and modulate the glucose production and utilization. Furthermore, deficiency of orexin action, particularly reduction of orexin 2 receptor-signaling, disrupts the mechanism for protection against insulin resistance associated with aging or induced by chronic high fat feeding in mice. Taken together, hypothalamic orexin system may manage multiple tasks to coordinate the interconnection among the arousal, feeding, circadian, and glucose homeostasis pathways.

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The aim of the present study was to evaluate the diagnostic accuracy and imaging patterns of colour Doppler ultrasonography (US) and compare it with grayscale US, 99m-Tc methoxyisobutylisonitrile (MIBI) scans, and combined US and MIBI scans in the preoperative diagnosis of parathyroid adenomas in patients with primary hyperparathyroidism (pHPT). From June 2007 to June 2011, 36 consecutive patients (seven men and 29 women) with pHPT underwent grayscale US, colour Doppler ultrasonography (CDUS), and 99m-Tc MIBI scans prior to parathyroidectomy with traditional unilateral neck dissection. All 36 patients with pHPT underwent parathyroidectomy at our university hospital. According to histopathology results, the sensitivity, specificity, and accuracy of MIBI and US scan were 88%, 94%, and 91%, and 70%, 100%, and 85%, respectively. The overall sensitivity and specificity of combined US and MIBI was 97% and 100% respectively. The overall sensitivity, specificity, and accuracy of CDUS in the correct diagnosis of parathyroid adenoma were 97%, 100%, and 98.6%, respectively. The sensitivity and specificity of US in the detection of parathyroid adenoma and differentiating it from other cervical masses reached up to 97% and 100%, respectively, by combining CDUS with grayscale evaluations of parathyroid adenoma.

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Periampullary malignant neoplasms have been increasing in Japan, mainly in response to an increase in the incidences of pancreatic cancer, and glucose intolerance due to deterioration of insulin secretion is an important problem. We investigated preoperative parameters to predict postoperative insulin secretion and the need for insulin therapy in patients undergoing pancreaticoduodenectomy (PD). Thirty-six patients with malignant neoplasms of periampullary lesions were enrolled. Preoperative pancreatic parenchymal thickness was evaluated by computed tomography. Insulin secretion and glucose tolerance were evaluated by a 75-g oral glucose tolerance test and an intravenous glucagon loading test. The relationships between postoperative insulin secretion and preoperative parameters and the cut-off values for predicting the need for postoperative insulin therapy for glycemic control were investigated. Pancreatic parenchymal thickness and other preoperative parameters, including the increment of serum C-peptide (Δ C-peptide), fasting plasma C-peptide (F-CPR), insulinogenic index (I.I.) and fasting plasma glucose (FPG), were significantly associated with postoperative insulin secretion. Multiple regression analyses revealed that preoperative Δ C-peptide or F-CPR was the most significant determinant of postoperative insulin secretion, followed by pancreatic parenchymal thickness. In the receiver operating characteristic curve, the best preoperative cut-off values for predicting the need for postoperative insulin therapy were a Δ C-peptide of 0.65 ng/mL, a F-CPR of 0.85 ng/mL and a pancreatic parenchymal thickness of 6.0 mm. Both preoperative insulin secretion and pancreatic parenchymal thickness effectively predict postoperative insulin secretion and identify subjects who need postoperative insulin therapy for glycemic control.

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The association between light exposure at night and sex hormone levels in utero has scarcely reported. We assessed the associations between sleep duration or being awake in the late evening hours, which can be as indicator of light exposure at night, and the maternal and umbilical blood hormone levels during pregnancy and at delivery among Japanese women. The data for 236 women and their newborns who visited a maternal clinic in Gifu, Japan, between May 2000 and October 2001 were analyzed. Maternal blood samples were obtained at approximately the 10th weeks, 29th weeks of gestation, and at delivery. Umbilical cord artery blood was immediately drawn after birth. Information for sleep during pregnancy was obtained by a self-administered questionnaire. The levels of estradiol and testosterone were measured using radioimmunoassay. Maternal serum testosterone level in the 10th week was higher among those who were awake at or after 1:00 a.m. than among those who were asleep at that time (P = 0.032). Maternal estradiol level in the 29th week was inversely associated with sleep duration on weekends (P = 0.043). Umbilical testosterone level at delivery inversely correlated with sleep duration on weekdays (P = 0.030). These associations were somewhat stronger among mothers with female offspring than those with male offspring. These results suggested that exposure to light at night might increase sex hormone levels during pregnancy.

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Age is an important prognostic factor in papillary thyroid carcinoma (PTC). In this study, we investigated the difference in prognosis of 7 subsets of PTC patients without distant metastasis at presentation or a history of radiation exposure (20 years or younger, 21-30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years, and older than 70 years). The lymph node recurrence rate was high in patients 20 years or younger and those older than 60 years. Distant recurrence and carcinoma death rates significantly elevated in patients older than 60 years. The incidence of significant extrathyroid extension markedly increased with age, although that of large node metastasis or extranodal tumor extension did not differ much among the 7 subsets. With the Kaplan-Meier method, lymph node recurrence rate was poor in patients 20 years or younger and in those older than 60 years. Poor distant recurrence-free and cause specific survivals of patients older than 60 years were identified in the series of PTC patients with and without these aggressive features. It is therefore suggested that 1) Lymph node recurrence rate was high in patients 20 years or younger and those older than 60 years and 2) prognosis, including distant recurrence-free survival and cause-specific survival, of patients older than 60 years was poor regardless of clinicopathological features of PTC at initial surgery.

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Medullary thyroid carcinoma (MTC) accounts for 1.4% of all thyroid malignancies in Japan. Here, we studied the validity of a staging system evaluated preoperatively (Stage), intraoperatively (intra-Stage), and pathologically (pStage) based on the 6^th and 7^th UICC TNM classifications. One hundred and nineteen MTC patients who did not show distant metastasis at diagnosis and underwent locally curative surgery were enrolled in this study (average follow-up period: 173.4 months). Twenty-year clinical (not biochemical) disease-free survival (DFS) rates of Stage I, II, III, and IVA patients based on the 6^th edition were 100, 88.2, 66.8, and 38.9%, respectively. DFS of Stage IVA patients was significantly poorer than that of Stage III patients (p = 0.03137). However, using the 7^th edition, only 1 patient was classified with Stage III. Intra-Stage III patients based on the 6th edition showed a significantly poorer DFS (20-year DFS 50.0%) than intra-Stage II patients (92.9%) (p = 0.02668), and DFS of intra-Stage IVA patients (38.9%) tended to be poorer than that of intra-Stage III patients (p = 0.05439). Only one patient was classified with intra-Stage III using the 7^th edition. In pStage, as many as 56 patients (47.1%) were classified with pStage IVA employing both editions. Taken together, Stage and intra-Stage were more useful to accurately discriminate high-risk patients than pStage, and their 6^th editions were better than 7^th editions. Although the number of patients was small, our data showed the possibility that intra-Stage in the 6^th edition was the best staging system for MTC patients.

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Several experiments have been carried out in order to find molecular markers that increase the diagnose accuracy of the Fine-Needle Aspiration (FNA), especially for thyroid lesions of undetermined significance. The growing number of published experiments on one or more of the different types of markers has started to justify the need to gather the pieces of information as a way to add evidence and guide the development of future research in the area. From the search arguments and criteria previously defined, 95 articles were selected from the electronic databases PUBMED, MEDLINE, SCOPUS and LILACS. From the 36 markers submitted to analysis and identified in preoperative FNA thyroid samples, only 10 (GAL3, CK-19, HBME-1, TPO, CD44, Telomerase, DAP IV, RAS, RET and BRAF) were assessed in more than two investigations, be it either in panel or individually. The minimum, medium and maximum values of sensibility, specificity, positive predictive value, negative predictive value and diagnose accuracy were obtained from the group of investigation, as well as the limitations and advantages of the use of each marker were identified. The BRAF mutation, for its unquestionable specificity, and the GAL3, for its regularity of average results obtained here, found in several locations in the cell as well as out of the cell, suggesting multiple functions of this molecule, were observed as holders of more expressive evidence in the effort of reducing the uncertainty of the diagnose in preoperative FNA of thyroid.

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Alcohol consumption is associated with type 2 diabetes. However, the relationship between alcohol consumption and β-cell function is still unclear. The aim of this study is to investigate the association between them. 675 Chinese men aged 20-75 years were recruited. The subjects were first classified into never drinkers, abstainers, light drinkers (0.1-19.9 g/day) , moderate drinkers (20.0-39.9 g/day) and heavy drinkers (≥ 40.0 g/day) and then, were further divided into two subgroups according to body mass index (BMI) (BMI<25kg/m² and BMI ≥ 25kg/m²). Analysis procedure was adjusted by the confounders including age, smoking status, BMI, waist circumference (WC), blood pressure, lipids and blood uric acid. Compared with never drinkers, alcohol consumption was associated with decreased homeostasis model assessment of β-cell function (HOMA-β) independent of BMI. The homeostasis model assessment of insulin resistance (HOMA-IR) was significantly correlated with alcohol consumption history in the group of BMI<25kg/m² and was significantly correlated with alcohol consumption in the group of BMI ≥ 25kg/m². The results suggest that alcohol consumption is associated with the β-cell dysfunction independent of BMI in Chinese community dwelling men.

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Recently, interference from cross-reacting peptides in plasma has been recognized as being responsible for inter-subject differences in active glucagon-like peptide-1 (GLP-1) values. An ethanol or solid-phase extraction step could reduce such interference. A working group of the Japan Diabetes Society now recommends the inclusion of an extraction step when measuring active GLP-1 values. We measured the active GLP-1 levels of 200 specimens derived from 10 subjects using both methods and compared the results. The active GLP-1 levels measured by extraction method for 169 specimens with values greater than 2.0 pM tended to be lower than those by direct method. However, the correlation between the GLP-1 levels measured by extraction and direct method was r=0.9225 (p < 0.0001). In one case, the active GLP-1 level obtained using the extraction method was significantly lower than that obtained using the direct method. Therefore, though there is a good correlation between the two methods, extraction is recommended for more accurate active GLP-1 measurements.

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Results from studies on the association of PTPN22 C1858T polymorphism with AITD risk are conflicting, we thereby perform this meta-analysis to derive a more precise effect on this possible association. Two investigators independently searched the PubMed, Embase, Wanfang and CNKI (China National Knowledge Infrastructure) databases. A total of 11 studies with 3764 AITDs cases and 3328 controls were finally identified. Statistically significant association was observed between PTPN22 C1858T polymorphism and AITD risk based on all studies (TT vs. CC, OR=2.18, 95%CI=1.31˜3.62; TC vs. CC, OR=1.50, 95%CI=1.29˜1.73; TT/TC vs. CC, OR=1.41, 95%CI=1.12˜1.78; TT vs. TC/CC, OR=2.00, 95%CI=1.21˜3.33). The results of subgroup analysis showed that: (1) regarding ethnic diversity, the variant genotypes TT/TC of C1858T were associated with a significantly increased AITD risk in Caucasians (TT/TC vs. CC, OR=1.41, 95%CI=1.09˜1.83) (2) regarding different countries, the statistically significantly association was observed in UK (TC vs. CC, OR=1.64, 95%CI=1.36˜1.98; TT/TC vs. CC, OR=1.65, 95%CI=1.37˜1.98) and other countries (including South Tunisia, Russia, Polish, Japanese) (TT vs. CC, OR=3.65, 95%CI=1.43˜9.33; TT vs. TC/CC, OR=3.41, 95%CI=1.34˜8.65). (3) regarding the subtypes of AITDs, patients with Graves’ disease (GD) had a significant higher degree of C1858T polymorphism (TT vs. CC, OR=2.35, 95%CI=1.36˜4.05; TC vs. CC, OR=1.46, 95%CI=1.12˜1.89; TT/TC vs. CC, OR=1.54, 95%CI=1.33˜1.80; TT vs. TC/CC, OR=2.16, 95%CI=1.25˜3.72), while no association was observed in patients with Hashimoto’s thyroiditis (HT). No publication bias was observed. Our results demonstrated that PTPN22 C1858T polymorphism was associated with AITD risk, especially in Caucasians.

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