Functional properties of synthetic N-acyl-L-homoserine lactone analogs of quorum-sensing gram-negative bacteria on the growth of human oral squamous carcinoma cells.

Quorum sensing is defined as the ability of microorganisms to sense their population density via the release of signaling molecules composed of acyl-homoserine lactone (AHL), which is a type of autoinducer (AI). Previous structure-activity relationship (SAR) studies demonstrated that the 3-oxo group, homoserine lactone of L-form, and long acyl side chain have crucial roles in apoptosis induction. Various types of synthetic AI analogs of Pseudomonas aeruginosa were prepared, and SAR study was conducted to determine their effects against human oral squamous carcinoma cells derived from gingival carcinoma Ca9-22 cells and tongue cancer SAS cells. Not only the antiproliferative potential but also the radiation-sensitizing effects against these cells were examined. It was found that antiproliferative activity partly depended on HSL structure and acyl side chain length. Moreover, a few compounds, compound 5 and 87, showed antiproliferative effects against both Ca9-22 and SAS cells, and also induced radiation-sensitizing effects against Ca9-22 cells. Compound 5 alone induced apoptotic cell death accompanied by sub-G1 phase accumulation in cell cycle and caspase-3 activation, and radiation-sensitizing effects of compound 5 could be attributed to enhanced apoptosis induction. In contrast, there were no remarkable alterations in cell cycle distribution in Ca9-22 treated with compound 87 alone or in combination. However, both compounds lack 3-oxo and their acyl side chain lengths are not necessarily long. This SAR study demonstrated that HSL analogs, which lacked the recommended characteristics for apoptosis induction clearly showed antiproliferative and radiation-sensitizing activity in Ca9-22 cells.

Successful long-term treatment with once-daily injection of low-dose octreotide in an aged patient with insulinoma.

The patient was an 83-year-old woman who was admitted to our hospital for evaluation and treatment of chronic hypoglycemia that was first identified 3 years earlier. Serum insulin and C-peptide levels were both elevated during hypoglycemia. Contrast abdominal computed tomography revealed a tumor in the body of the pancreas with blushing during the early phase, and insulinoma was diagnosed. The patient declined surgery because of advanced age, so treatment was started with octreotide, a somatostatin analogue. Hypoglycemia has been successfully controlled with low-dose, once-daily octreotide over 33 months. Few reports have described long-term octreotide administration for benign insulinoma. Moreover, this case is interesting from the perspective of hypoglycemic control using only low-dose, once-daily octreotide. Although somatostatin may induce hypoglycemia in insulinoma, treatment may be useful in patients who are not candidates for surgery, provided that careful monitoring is maintained.

Discrepancies in results of low-and high-dose dexamethasone suppression tests for diagnosing preclinical Cushing's syndrome.

According to the diagnostic criteria for adrenal preclinical Cushing's syndrome (PreCS) established by a group headed by the Ministry of Health, Labor and Welfare (MHLW), low- and high-dose dexamethasone suppression tests (DSTs) must be performed to prove autonomous cortisol secretion, i.e., > or =3 microg/dL serum cortisol following 1-mg DST administration, and > or =1 microg/dL serum cortisol following 8-mg DST administration. However, discrepancies have been documented in the results of low-and high-dose DSTs. We therefore investigated the validity of the DST for diagnosing PreCS by performing 1-mg and 8-mg DSTs in 39 patients with adrenal incidentaloma, but no characteristic Cushingoid symptoms. In about half of these patients (20/39, 51.3%), high-dose DST was positive but low-dose was negative, and one or more of the other abnormalities of hypothalamus-pituitary-adrenal axis dysfunction was seen in 75% of these patients. Furthermore, no significant difference in incidence of glucose intolerance and hypertension was noted in patients with positive high-dose DST and negative low-dose DST compared with patients with positive low- and high-dose DST. Under the current MHLW diagnostic criteria, patients with positive high-dose DST and negative low-dose DST are not diagnosed with PreCS, but some of these patients should be. Discrepancies in the results of low- and high-dose DSTs appear attributable to the current cutoff values, and further investigations are necessary to resolve these discrepancies.