Thyroid Transcription Factor-1 Facilitates Cerebrospinal Fluid Formation by Regulating Aquaporin-1 Synthesis in the Brain

In the brain, aquaporin-1 (AQP-1), a water channel for high osmotic water permeability, is mainly expressed in the apical membrane of the ventricular choroid plexus and regulates formation of cerebrospinal fluid (CSF). Although the physiology of AQP-1 has been the subject of several publications, much less is known about the trans-acting factors involved in the control of AQP-1 gene expression. Here we report that TTF-1, a homeodomain-containing transcriptional regulator, is coexpressed with AQP-1 in the rat brain choroid plexus and enhances AQP-1 gene transcription by binding to conserved core TTF-1-binding motifs in the 5'-flanking region of the AQP-1 gene. Intracerebroventricular administration of an antisense TTF-1 oligodeoxynucleotide significantly decreased AQP-1 synthesis and reduced CSF formation. In addition, blockade of TTF-1 synthesis increased survival of the animals following acute water intoxication-induced brain edema. These results suggest that TTF-1 is physiologically involved in the transcriptional control of AQP-1, which is required for CSF formation

Prevalence of Thyroid Cancer at a Medical Screening Center: Pathological Features of Screen-detected Thyroid Carcinomas

Purpose: To assess the incidence of thyroid malignancy in an adult population screened by high-resolution ultrasonography at a medical screening center and to compare the clinical and pathological features of screen-detected thyroid carcinomas to symptomatic overt thyroid carcinomas. Materials and Methods: We calculated the prevalence of screen-detected thyroid cancer at a medical screening center using highresolution ultrasonography and fine needle aspiration. We then compared the clinical and pathological features of screendetected thyroid cancers (n = 46) to clinical symptomatic thyroid cancers (n = 157). We evaluated age, gender, size, perithyroidal extension, lymphovascular extension, stage, histological lymph node metastasis, and the type of cancer. We also compared the above findings of micropapillary carcinomas to papillary thyroid carcinomas that were larger than 1 cm i

Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition

Background Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are currently used to treat patients with diabetes. Previous studies have demonstrated that treatment with SGLT-2 inhibitors is accompanied by altered metabolic phenotypes. However, it has not been investigated whether the hypothalamic circuit participates in the development of the compensatory metabolic phenotypes triggered by the treatment with SGLT-2 inhibitors. Methods Mice were fed a standard diet or high-fat diet and treated with dapagliflozin, an SGLT-2 inhibitor. Food intake and energy expenditure were observed using indirect calorimetry system. The activity of hypothalamic neurons in response to dapagliflozin treatment was evaluated by immunohistochemistry with c-Fos antibody. Quantitative real-time polymerase chain reaction was performed to determine gene expression patterns in the hypothalamus of dapagliflozin-treated mice. Results Dapagliflozin-treated mice displayed enhanced food intake and reduced energy expenditure. Altered neuronal activities were observed in multiple hypothalamic nuclei in association with appetite regulation. Additionally, we found elevated immunosignals of agouti-related peptide neurons in the paraventricular nucleus of the hypothalamus. Conclusion This study suggests the functional involvement of the hypothalamus in the development of the compensatory metabolic phenotypes induced by SGLT-2 inhibitor treatment

Managing Thyroid Microcarcinomas

Papillary thyroid microcarcinomas (PTMCs) are the most common form of classic papillary thyroid carcinoma (PTC). PTMCs are typically discovered by fine-needle-aspiration biopsy (FNAB), usually with sensitive imaging studies, or are found during thyroid surgery in a patient without a previously known history of thyroid carcinoma. However, the definition of PTMC has not always been universally accepted, thus creating controversy concerning the diagnosis and treatment of PTMC. The aim of this review is to summarize the clinical features of PTMC and identify the widely differing opinions concerning the diagnosis and management of these small ubiquitous thyroid tumors