Anterior Cutaneous Nerve Entrapment Syndrome Possibly Triggered by Oral Contraceptives.

We herein report a teenage girl who had been taking oral contraceptive pills for three months and complained of left lower abdominal pain that had continued for two months. A physical examination indicated anterior cutaneous nerve entrapment syndrome (ACNES), although no abnormality was found in various biochemical and imaging examinations. The pain was only transiently ameliorated by trigger-point injection, and neurectomy surgery was eventually effective. Sex steroids can be involved in the progress of local tissue edema causing ACNES. ACNES should be considered in cases of abdominal pain in patients taking oral contraceptives.

Interaction of ovarian steroidogenesis and clock gene expression modulated by bone morphogenetic protein-7 in human granulosa cells.

A functional link between clock gene expression and ovarian steroidogenesis was studied using human granulosa KGN cells. Similarities between changes in the mRNA and protein expression levels of Bmal1 and Clock and those of Per2 and Cry1 were found in KGN cells after treatment with forskolin. Among the interrelationships between the expression levels of clock and steroidogenic factors, Clock mRNA had a strongly positive correlation with P450arom and a negative correlation with 3ßHSD. Knockdown of Clock gene by siRNA resulted in a significant reduction of estradiol production by inhibiting P450arom expression, while it induced a significant increase of progesterone production by upregulating 3ßHSD in KGN cells treated with forskolin. Moreover, BMP-7 had an enhancing effect on the expression of Clock mRNA and protein in KGN cells. Thus, the expression levels of Clock, being upregulated by forskolin and BMP-7, were functionally linked to estradiol production and progesterone suppression by human granulosa cells.

Effect of the interaction of metformin and bone morphogenetic proteins on ovarian steroidogenesis by human granulosa cells.

In the present study, we studied the effects of metformin and its interactions with the actions of bone morphogenetic proteins (BMPs) on ovarian steroidogenesis. It was revealed that metformin treatment enhanced progesterone production by human granulosa KGN cells and rat primary granulosa cells induced by forskolin and FSH, respectively. In human granulosa cells, it was found that metformin treatment suppressed phosphorylation of Smad1/5/9 activated by BMP-15 compared with that induced by other BMP ligands. Moreover, metformin treatment increased the expression of inhibitory Smad6, but not of that Smad7, in human granulosa cells, while metformin had no significant impact on the expression levels of BMP type-I and -II receptors. Thus, the mechanism by which metformin suppresses BMP-15-induced Smad1/5/9 phosphorylation is likely, at least in part, to be upregulation of inhibitory Smad6 expression in granulosa cells. The results suggest the existence of functional interaction between metformin and BMP signaling, in which metformin enhances progesterone production by downregulating endogenous BMP-15 activity in granulosa cells.

Incretins modulate progesterone biosynthesis by regulating bone morphogenetic protein activity in rat granulosa cells.

The effects of incretins on ovarian steroidogenesis have not been clarified. In this study, we investigated the effects of incretins, including GIP and GLP-1, on ovarian steroidogenesis using rat primary granulosa cells. Treatment with incretins significantly suppressed progesterone synthesis in the presence of FSH, and the effect of GIP was more potent than that of GLP-1. In contrast, incretins had no significant effect on estrogen synthesis by rat granulosa cells. In accordance with the effects of incretins on steroidogenesis, GIP and GLP-1 suppressed the expression of progesterogenic factors and enzymes, including StAR, P450scc, 3ßHSD, but not P450arom, and cellular cAMP synthesis induced by FSH. In addition, incretins moderately increased FSHR mRNA expression in granulosa cells. Of note, treatment with GIP, but not treatment with GLP-1, augmented Smad1/5/8 phosphorylation and transcription of the BMP target gene Id-1 induced by BMP-6 stimulation, suggesting that GIP upregulates BMP receptor signaling that can inhibit FSH-induced progesterone synthesis in rat granulosa cells. On the other hand, BMP-6 treatment suppressed the expression of GIP receptor but not that of GLP-1 receptor. Expression of the BMP type-I receptor ALK-3 was upregulated by treatment with GIP and GLP-1 and that of ALK-6 was also increased by GIP, while inhibitory Smad6 expression was impaired by GIP and GLP-1 in rat granulosa cells. Collectively, the results indicate that incretins, particularly GIP, impair FSH-induced progesterone production, at least in part, by upregulating BMP signaling in rat granulosa cells. The modulatory effects of incretins on endogenous BMP activity may be applicable to treatment of dysregulated steroidogenesis such as polycystic ovary syndrome.

Soft tissue hematoma of the neck due to thyroid rupture with unusual mechanism.

INTRODUCTION: Massive bleeding from the thyroid gland causing airway compromise secondary to indirect neck trauma is rare. PRESENTATION OF CASE: An 89-year-old woman was transferred to our emergency department due to anterior neck pain after a traffic accident. She had been propelled forward and struck her head on the front mirror during emergency braking. Airway patency was confirmed at the first contact. Although her vital signs were stable at presentation, she gradually suffered from respiratory distress and severe dyspnea, implying airway compression, therefore requiring endotracheal intubation. Computed tomography (CT) revealed a large, encapsulated hematoma in the left thyroid gland lobe extending to the upper mediastinum. Contrast-enhanced CT demonstrated an extravasation of the contrast agent around the left superior thyroid artery. The left thyroid artery was ligated and the hematoma was removed immediately. She had a favorable course without further complications and was discharged 36days after admission. DISCUSSION: Airway management is the most important consideration in patients with thyroid injury. Treatment should be customized depending on the degree of respiratory distress resulting from of either involvement of the direct airway or secondary compression. CONCLUSION: Although hemorrhage from the thyroid gland without blunt trauma is rare, emergency physicians should regard possible thyroid gland rupture in patients with swelling of the neck or acute respiratory failure after direct/indirect trauma to the neck. Observation or operative management for limited or expanding hematoma are appropriately based on fundamental neck trauma principles.