Vitamin D receptor (VDR), a nuclear receptor that regulates calcium homeostasis, has been found to function as a receptor for secondary bile acids. Because the in vivo role of VDR in bile acid metabolism remains unknown, we investigated the effect of VDR activation in a mouse model of cholestasis. We treated mice with 1␣-hydroxyvitamin D 3 [1␣(OH)D 3 ] after bile duct ligation (BDL) and examined mRNA expression and cytokine levels. 1␣(OH)D 3 treatment altered the expression of genes involved in bile acid synthesis and transport in the liver, kidney, and intestine but did not decrease bile acid levels in the plasma and liver of BDL mice. 1␣(OH)D 3 treatment suppressed mRNA expression of proinflammatory cytokines in the liver and strongly decreased the plasma levels of proinflammatory cytokines in BDL mice. These findings indicate that 1␣(OH)D 3 regulates a network of bile acid metabolic genes and represses proinflammatory cytokine expression in BDL mice. VDR ligands have the potential to prevent the cholestasis-induced inflammatory response.

Thyroid hemiagenesis is a very rare anomaly. We herein report a case with right thyroid lobe agenesis, which was incidentally found during the assessment of primary hyperparathyroidism. A 42-year-old male presenting with urinary lithiasis was suspected of having primary hyperparathyroidism, and had elevated levels of both serum calcium and intact parathyroid hormone. Both computed tomography and ultrasonography demonstrated the absence of right thyroid lobe and a mass of 1 cm in diameter at the left lower pole of the thyroid. The patient underwent lower left parathyroidectomy, which confirmed the right thyroid hemiagenesis, as well as the absence of both upper and lower right parathyroid glands. The resected left lower parathyroid gland was pathologically diagnosed as adenoma. The postoperative course was favourable and he was discharged on the 2nd day after surgery, without complications.

The environmental pollutant 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) is known to cause a wide variety of toxic effects, including hepatotoxicity, by way of the aryl hydrocarbon receptor (AHR). Although inducible expression of cytochrome P450 (CYP) 1A1 and CYP1A2 is associated with liver injury caused by high-dose TCDD, the specific role of the AHR-CYP1 cascade in hepatotoxicity remains unclear. We investigated the effects of AHR activation under conditions of cholestasis. We administered oral TCDD to mice at a dose that can effectively induce Cyp1 gene expression without overt liver toxicity and then ligated their bile ducts. TCDD pretreatment enhanced bile duct ligation (BDL)-induced increases in liver and plasma bile acids, bilirubin, and aminotransferases. Histology of TCDD-pretreated BDL mice revealed massive hepatic necrosis without any increase in number of apoptotic cells. Whereas induction of AHRtarget genes by TCDD was observed similarly in sham-operated as well as in BDL mice, TCDD pretreatment of BDL mice altered the expression of hepatic genes involved in bile acid synthesis and transport. Increased plasma proinflammatory cytokines, tumor necrosis factor and interleukin-1β, in BDL mice were further elevated by TCDD pretreatment. Liver injury by TCDD plus BDL, such as increased plasma bile acids, bilirubin and aminotransferases, liver necrosis, and increased tumor necrosis factor production, was exaggerated in Cyp1a1/1a2(−/−) double knockout mice. These findings indicate that TCDD aggravates cholestatic liver damage and that the presence of CYP1A1 and CYP1A2 plays a protective role in liver damage caused by TCDD and BDL.

Measuring CYP3A4 expression immunohistochemically in the primary breast cancer lesion was useful for predicting the treatment response to DOC of tumors that recurred after a long interval.

This study showed that menstruation resumed after treatment at higher rates in younger patients. However, because it is highly likely that ovarian function will be destroyed by the treatment even in young patients, it is considered necessary to explain the risk to patients and obtain informed consent before introducing this treatment modality.