Comparison of pre- vs. postmeal administration of miglitol for 3 months in type 2 diabetic patients.

AIM: alpha-Glucosidase inhibitors (alphaGIs) primarily modify postprandial plasma glucose levels and should be taken just before meals. We previously demonstrated that a single administration of miglitol within 30 min after the start of a meal was equally effective as when administered just before a meal. We here compared pre- vs. postmeal administration of miglitol for 3 months in type 2 diabetic patients. METHODS: Thirty-one type 2 diabetic outpatients who had never been treated with insulin injections or alphaGIs were randomized to two groups: patients in group A were asked to take miglitol just before meals, while patients in group B were asked to take miglitol after meals. We measured 1,5-anhydroglucitol (1,5-AG) and HbA(1C) levels in these patients. RESULTS: The administration of miglitol after meals for a 3-month period decreased HbA(1C) and increased 1,5-AG levels to the same extent as when administered just before meals. The incidence of adverse effects seemed to be unrelated to the timing of the miglitol administration. CONCLUSIONS: Our results suggest that if patients have difficulty remembering to take miglitol just before meal, they should be instructed to take the medicine together with other medicine(s) after the meal; this instruction may improve the treatment compliance of diabetic patients.

Cytotoxic alkaloids of Pachysandra terminalis.

Four steroidal alkaloids, epipachysamines B (1) and E (2), pachystermine A (3) and pachysamine E (4), were isolated as cytotoxic principles from the MeOH extract of the stems of Pachysandra terminalis SIEB. et ZUCC. (Buxaceae). These alkaloids showed cytotoxic activity against P388 and P388/ADR leukemia cells in vitro. Three of the alkaloids (1-3) were previously isolated from this plant material, and this is the first report of their cytotoxic activity. Pachysamine E (4) is a new alkaloid.

Novel antiallergic and antiinflammatory agents. Part II: Synthesis and pharmacology of TYB-2285 and its related compounds.

A series of m-bis(glycoloylamino)benzene derivatives was synthesized by treatment of the corresponding m-diaminobenzene derivatives with glycoloyl chloride derivatives in pyridine. Hydrolysis of acetyl compounds gave hydroxy derivatives, from which other acyl derivatives could be synthesized. These compounds were tested in the rat PCA (passive cutaneous anaphylaxis) assay by oral administration. Benzonitrile derivatives (4c, 5c, 6c, 4h, 5h) exhibited notable inhibition in this assay. Compounds 5c and 6c also showed remarkable inhibition of eosinophil adhesion to TNF- (tumor necrosis factor) alpha-treated HUVEC (human umbilical vein endothelial cells) in the range of 10(-8)-10(-5) M. Compound 5c is now under investigation in Japan as TYB-2285 (Figure 1) for asthma and atopic dermatitis in phase II clinical studies.

Sex-steroid receptor mechanism related to neuronal aromatase and the stigmoid body.

Recent immunohistochemical analyses of rat brains have established the presence of neuronal aromatase and stigmoid body in interfaces of a sex-steroid/brain axis. Aromatase P450-immunoreactive (AROM-I) neurons, which are present only during embryonic Day 16 to postnatal Day 2 (E16-P2), are found in the anterior medial preoptic nucleus, the periventricular preoptic nucleus, and the ventromedial hypothalamic nucleus. The largest AROM-I cell-group localized in the medial preoptico-amygdaloid neuronal arc (mPO-AM) shows a peak during E18-P2 and gradually diminishes after the perinatal days (but still retains the immunoreactivity in adults). In adults, other groups of AROM-I neurons emerge in the lateral septum, the central amygdaloid nucleus, and the bed nucleus of the stria terminalis. Male-predominant sex difference for aromatase expression has been detected at least in the young-to-adult mPO-AM, reflecting sexually distinct endocrine and behavioral responses in the rat reproductive functions. These results suggest the presence of distinct brain-aromatases with different regulatory systems. Neuronal aromatase may modulate development of sexual dimorphism in neonates and activation of reproductive functions in adults. The stigmoid bodies, marked by placental aromatase-associated antigen X-P2 (PAX) antiserum, are also frequent in the sex-steroid targets of rat brains and intimately coexist with estrogen receptors in the mPO-AM of young females. The neuronal inclusion, suspected as a RNA/protein conglomerate, appears to be induced by the decrease of androgen and/or the increase of estrogen, especially as a result of subneuronal aromatic switching into the estrogenous state. The neuronal aromatase and stigmoid body may play important roles in the pre- and post-receptor steps of subneuronal sex-steroids actions for brain sexual differentiation or induction of reproductive functions.

Coexistence of the stigmoid body and estrogen receptor in some neuronal groups involved in rat reproductive functions.

Recent immunohistochemical studies have suggested that the forebrain distribution of stigmoid bodies, marked by an antibody against placental aromatase-associated antigen X-P2 (PAX), overlaps with that of the common binding sites of androgen and estrogen. In the present light- and electron-microscopy study the coexistence of stigmoid bodies and estrogen receptors (EsR) is immunohistochemically examined and quantitatively analyzed in the medial preoptic region, part of the bed nucleus of the stria terminalis and part of the medial amygdaloid nucleus of young female rats. Light microscopy with double immunostaining for PAX and EsR in all three regions indicates that 75-84% of the total of PAX-immunoreactive stigmoid structures are present in neurons which also contain EsR-immunoreactive nuclei, and that 75-78% of EsR-immunoreactive neurons contain PAX-immunoreactive inclusions. Electron microscopic analysis confirms that 70-80% of stigmoid body-containing neurons have EsR-immunoreactive nuclei. These results indicate that the majority of the stigmoid bodies and EsRs intimately coexist, strongly suggesting a functional interrelationship in brain regions which are involved in rat reproductive functions. Stigmoid bodies may play a role in subneuronal EsR mechanisms associated with aromatization in these sex steroid targets in rat brain.

Screening of aromatase-containing neurons in rat forebrain: an immunohistochemical study with antibody against human placental antigen X-P2 (hPAX-P2).

Aromatase-containing neurons were immunohistochemically examined in rat brains by using a polyclonal antibody against human placental antigen. The antibody recognizes cytochrome P-450 portion of aromatase, an enzyme converting androgen to estrogen. A large group of strongly immunoreactive cells was identified in the ventral pallidum, which extends caudally from the area surrounding the islands of Calleja. Other strongly or moderately stained cell groups were observed in the cerebral cortex, the amygdaloid area, the nucleus of the diagonal band, and the area anterior to the posterior commissure. Only a few stained cells were present in the medial preoptic region. These findings cast doubt upon the previous assumption, based on biochemical analysis of tissue samples, that the center of the aromatizing system is in the medial preoptic region. They indicate instead that most aromatase-containing neurons of rats lie within the ventral pallidum ventromedially adjacent to the preoptic area.