Measurement of changes in CO2 generated from propionate in Caenorhabditis elegans using novel 13CO2 gas analysis.

Caenorhabditis elegans contains two pathways for propionate metabolism, the vitamin B12-dependent and shunt pathways, which are similar to those in humans. In this study, we monitored the changes in propionate metabolism in the whole body of C. elegans using novel 13CO2 gas analysis. We measured the increase in 13CO2 excreted in the air after administering [1-13C]-labeled propionate ([13C]propionate) to the worms. The 13CO2 generated from [13C]propionate in C. elegans increased in a dose-dependent manner, reaching a maximum at 48 h. Enhanced expression of propionate metabolism-related genes was observed after administration of propionate. Knockdown of mmcm-1, which encodes the rate-limiting enzyme of the propionate metabolism, using RNAi reduced 13CO2 excretion. Thus, 13CO2 gas analysis could be confirmed 13CO2 excretion associated with changes in the metabolism of [13C]propionate in nematodes. This analysis can contribute to further understanding of the physiological effects of short-chain fatty acids.

Body heat responsive gelation of methylcellulose formulation containing betaine.

We examined a methylcellulose (MC) formulation that gels at body temperature for enteral alimentation. Betaine was found to have a lowering effect on the gelation temperature of the MC solution. The thermal gelation temperature of a body heat-responsive (BHR) gelling MC formulation, consisting of 2% MC, 15% glucose, 1.2% sodium citrate, and 3.5% betaine mixture, was approximately 32 °C, indicating that it could gel in response to body heat. Glucose release from the BHR gels was delayed at 37 °C in an in vitro study. In rats, oral administration of BHR gelling MC formulation delayed an increase in blood glucose and appearance of 13CO2 in expired air in a 13C-acetate breath test in comparison with the control. These results suggested that the BHR gelling MC formulation was gelled in the stomach and delayed gastric emptying after oral administration and glucose in the gels was absorbed slowly.

Methylseleninic acid (MSA) inhibits 17ß-estradiol-induced cell growth in breast cancer T47D cells via enhancement of the antioxidative thioredoxin/ thioredoxin reductase system.

The purpose of this study was to clarify the cell growth inhibitory mechanism of human breast cancer cells caused by selenium (Se) compounds. In the presence of 17ß-estradiol (E(2)) at physiological concentrations, growth of estrogen receptor α (ERα)-positive T47D cells was markedly inhibited by 1 × 10(-6) mol/L methylseleninic acid (MSA) with no Se related toxicity.Under conditions where cell growth was inhibited, MSA decreased ERα mRNA levels and subsequent protein levels; further decreasing expression of estrogen-responsive finger protein (Efp) which is a target gene product of ERα and promotes G2/M progression of the cell cycle. Therefore, the decline in Efp expression is presumed to be involved in G2 arrest. Coincidentally, the antioxidative thioredoxin/ thioredoxin reductase (Trx/TrxR) system in cells was enhanced by the synergistic action of E(2) and MSA. It has been reported that ROS-induced oxidative stress enhanced ERα expression. E(2) increased production of intracellular ROS in T47D cells. Meanwhile, MSA significantly decreased E(2)-induced ROS accumulation. From these results, activation of the Trx/TrxR system induced by the coexistence of MSA and E(2) suppresses oxidative stress and decreases expression of ERα, and finally induces the growth arrest of T47D cells through disruption of ERα signaling.

Cushing's syndrome caused by an ectopic pituitary adenoma of the sphenoid sinus: Adrenal crisis after partial resections of the adenoma.

A 60-year-old woman with an 8-year history of Cushing's syndrome was evaluated. Biochemical data were consistent with those of Cushing's disease. Plasma ACTH levels responded paradoxically to GnRH. MRI demonstrated a large tumor occupying the sphenoid sinus, which was enhanced by gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). The pituitary gland was normal in shape and was located in the sella turcica without dislocation. The pituitary gland and the sphenoid tumor could be distinguished by the obvious difference in their MRI intensities. Three consecutive partial resections of the sphenoid tumor were performed, but plasma ACTH and cortisol levels remained high just after the third operation. Histological studies revealed a chromophobe adenoma immunohistochemically positive for ACTH. However, adrenal crisis occurred 3 months after the third operation during reserpine administration ( 1.5 mg/day for approximately 2 mo) for the treatment of Cushing's syndrome due to the residual tumor in the sphenoid sinus. Subsequent MRI showed no change in the tumor shadow, and the paradoxical response of plasma ACTH levels to GnRH remained unchanged. The fourth operation reconfirmed the existence of the ACTH-producing adenoma in the sphenoid sinus. There was no anatomical interaction between the sphenoid tumor and the pituitary gland, and, histologically, no tumor cells were present in the pituitary gland. These findings suggest that the tumor is an ACTH-producing ectopic pituitary adenoma arising from the sphenoid sinus. The patient has been in remission for 4 years on glucocorticoid replacement therapy. The factors responsible for the adrenal crisis were not well understood, although reserpine administration might have had some role.

Adrenal and retroperitoneal mixed neuroendocrine-neural tumors.

Four cases of mixed neuroendocrine-neural tumors composed of pheochromocytoma and neuroblastoma elements (including ganglioneuroma and ganglioneuroblastoma) were studied for the presence of catecholamine-synthesizing enzymes, neuroendocrine markers, and peptide hormones with clinicopathological correlations. Paroxysmal hypertension with hypercatech olaminemia was observed in 3 patients. One patient had an extremely elevated level of dopamine. The location of the tumor was in the adrenal glands in 2 patients and in the retroperitoneum in the other 2. Numerous electron-dense granules in the cytoplasm and neural processes with abundant neurotubules were characteristic of mixed neuroendocrine-neural tumors. Immunohistochemical study revealed that catecholamine-synthesizing enzymes were present in both components of the pheochromocytoma and neuroblastoma group, but phenylethanolamine N-methyltransferase was detectable only in epinephrine-producing tumors. Chromogranin and neurofilament immunoreactivities were present in both components; however, the intensity of chromogranin immunoreactivity was stronger in pheochromocytoma than in the other components. In contrast, neurofilament positivity was stronger in the neuroblastoma group than it was in pheochromocytoma. Multiple peptide hormones were immunoreactive in both components. Neuropeptide Y and met-enkephalin-positive cells were numerous in both; cells containing vasoactive intestinal peptide and somatostatin were less common but were comparatively more frequently found in ganglion cells than in pheochromocytoma cells.