A black adrenal adenoma difficult to be differentiated from a malignant adrenal tumor by CT,MRI, scintigraphy and FDG PET/CT examinations

Black adrenal adenoma (BAA) is an adrenal adenoma which contains lipofuscin and has a black or brown appearance. Preoperative diagnosis of BAA is difficult because it is diagnosed by pathologic findings. We report a case of an incidentally discovered non-hyperfunctioning BAA in the left adrenal gland of a 58-year-old man. It showed an oval lipid-poor mass, 3 cm × 2 cm in size on computed tomography (CT) and magnetic resonance imaging (MRI), no avid uptake of ¹³¹I-norcholesterol and ¹²³I-meta-iodobenzylguanidine (MIBG) on scintigraphy, and intense avid uptake of ¹⁸F-fluorodeoxyglucose (FDG) on positron emission tomography–CT (PET/CT). FDG PET/CT showed that it was a hypermetabolic lesion, more intense than the activity of the liver, and the maximum standardized uptake value was 5.6 on 1-h early imaging and 8.3 on 2-h delayed imaging, suggesting a malignant tumor. BAA is a clinically rare benign adrenal adenoma, but it should be kept in mind that BAA may exhibit false-positive results for malignancy or inconclusive results for benignity with modern imaging modalities including CT, MRI, adrenal scintigraphy with radiolabelled cholesterol and radiolabelled MIBG, and FDG-PET like this case.     

Sitagliptin, a dipeptidyl peptidase-4 inhibitor, decreases systolic blood pressure in Japanese hypertensive patients with type 2 diabetes

Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a newly developed oral hypoglycemic agent. Sitagliptin increases the level of glucagon-like polypeptide (GLP)-1 that increases insulin secretion. In addition, GLP-1 decreases salt intake and increases urinary salt excretion. Therefore, the sitagliptin treatment might lower blood pressure in hypertensive patients with type 2 diabetes. It also remains to be examined whether the reduction in blood pressure with sitagliptin treatment is related to the blood glucose improvement and the body weight decrease. To identify beneficial effects of sitagliptin treatment, we administered sitagliptin (50 mg) on alternate days to seventeen type 2 diabetes outpatients with insufficient blood glucose control (8 males and 9 females; mean age of 67.1 years). The patients were also treated with oral hypoglycemic agents and antihypertensive drugs for six months before and during the sitagliptin administration. We measured the level of hemoglobin (Hb) A1c, systolic blood pressure (SBP), and body mass index (BMI) for up to six months thereafter. Their BMIs remained unchanged. The levels of HbA1c were dropped from 6.5 ± 0.3% to 5.8 ± 0.3%, while SBP was also dropped from 130.0 ± 37.2 mmHg to 119.7 ± 9.4 mmHg. However, the degree of the decrease in HbA1c levels was not significantly correlated with that of SBP (r = 0.24). In conclusion, the present findings suggest that sitagliptin lowers SBP without reducing BMI, independent of the blood glucose reduction. The hypotensive effect is apparent with the alternate-day regimen of sitagliptin at a lower dose compared to the everyday medication.     

A role of oral bacteria in bisphosphonate-induced osteonecrosis of the jaw

No consensus has yet been reached to associate oral bacteria conclusively with the etio-pathogenesis of bisphosphonate-induced osteonecrosis of the jaw (BONJ). Therefore, the present study examined the effects of oral bacteria on the development of BONJ-like lesions in a mouse model. In the pamidronate (Pam)-treated mice, but not control non-drug-treated mice, tooth extraction followed by oral infection with Fusobacterium nucleatum caused BONJ-like lesions and delayed epithelial healing, both of which were completely suppressed by a broad-spectrum antibiotic cocktail. Furthermore, in both in vitro and in vivo experiments, the combination of Pam and Fusobacterium nucleatum caused the death of gingival fibroblasts (GFs) and down-regulated their production of keratinocyte growth factor (KGF), which induces epithelial cell growth and migration. Therefore, in periodontal tissues pre-exposed to bisphosphonate, bacterial infection at tooth extraction sites caused diminished KGF expression in GFs, leading to a delay in the epithelial wound-healing process that was mitigated by antibiotics.     

Expression and possible immune-regulatory function of ghrelin in oral epithelium

Originally found in stomach mucosa, ghrelin is a peptide appetite hormone that has been implicated as an immuno-modulatory factor. Ghrelin has also been found in salivary glands and saliva; however, its expression patterns and biological properties in the oral cavity remain unclear. Therefore, we investigated the expression patterns of ghrelin in saliva, gingival crevicular fluid (GCF), and gingival tissue, as well as its in vitro effects on IL-8 production by TNF-α or LPS-stimulated oral epithelial cells. In the clinical samples obtained from 12 healthy volunteers, the concentration of ghrelin in GCF remarkably exceeded that detected in saliva. The expression of ghrelin mRNAs and growth hormone secretagogue (GHS) receptors could be detected in human oral epithelial cells. Immunohistochemical analysis revealed the expression of ghrelin in gingival epithelium, as well as in fibroblasts in the lamina propria. Ghrelin increased intracellular calcium mobilization and cAMP levels in oral epithelial cells, suggesting that ghrelin acts on epithelial cells to induce cell signaling. Furthermore, synthetic ghrelin inhibited the production of IL-8 from TNF-α or LPS-stimulated oral epithelial cells. These results indicate that ghrelin produced in the oral cavity appears to play a regulatory role in innate immune responses to inflammatory infection.     

Serum adipocyte fatty acid-binding protein is independently associated with complex coronary lesions in patients with stable coronary artery disease

The association between circulating adipocyte fatty acid-binding protein (A-FABP) levels and coronary artery disease (CAD) is reported. We assessed whether plasma A-FABP levels are associated with angiographic coronary lesion morphology in patients with stable CAD. Serum A-FABP levels were analyzed in 115 patients with stable CAD (mean age 69 ± 10 years; 80 % men). These patients were angiographically studied and divided into two groups: simple lesions (n = 34) and complex lesions (n = 81). We also compared 50 age- and gender-matched controls with no evidence of CAD. Serum A-FABP levels in patients with stable CAD were significantly higher than those in controls. In patients with stable CAD, serum A-FABP levels were significantly higher in patients with complex lesions than in those with simple lesions: median (25th–75th percentile), 23.4 (17.7–30.8) vs 18.2 (12.2–24.7) ng/ml, P < 0.01. Serum A-FABP levels were also significantly associated with angiographic scores of extent of coronary lesion (r = 0.21, P = 0.02). Multiple logistic analysis that included dyslipidemia, statin therapy, and extent score demonstrated that serum A-FABP was independently associated with complex lesions. The multiple adjusted odds ratio for a complex lesion with a serum A-FABP level (per doubling) was 2.38 (95 % confidence interval, 1.03–6.41; P = 0.03). High serum A-FABP levels were significantly associated with complex coronary lesions in patients with stable CAD, suggesting that high A-FABP levels may be involved in coronary plaque vulnerability.