We determined the critical period for cleft palate formation in the presence of all-trans-retinoic acid (RA) and defined anomalous patterns within the variants of palatal rugae. The total incidence of variant patterns of palatal rugae in rat fetuses treated with RA at 40 mg/kg on gestation days 13 and 14 dramatically increased with concurrent induction of cleft palate. Correspondence analysis connected the variant patterns of palatal rugae, such as median discontinuity, extra peaks, supernumerary ruga (extra type), shortness, fusion, and bifurcation, with cleft palate. Therefore, these variants were concluded to be anomalous. The incidence of the anomalous patterns of palatal rugae was about 10 times that of cleft palate, and consequently, these anomalies might be sensitive indicators of the teratogenicity of a chemical.

Animals↗

PubMedDate not supplied

Alzheimer's disease and estrogen.

The preventive effect of estrogen on Alzheimer's disease (AD) has become clear with epidemiological data. Therapeutic effects of estrogen have not yet been established. In this presentation, we report our new basic and clinical data. The estrogen receptor, (ER)alpha, and ERbeta mRNA were investigated in rat brain. Estradiol-17beta (E(2)) treatment following OVX reduced the levels of ERalpha mRNA in the hypothalamus. In the substantia innominata (SI), the number of choline acetyltransferase immunoreacive cells increased significantly in the estrogen treatment rat. The neurons in SI projecting to the forebrain cortex contained ERalpha. Increasing amounts of intracellular calcium, peroxidation, and apoptosis with amyloid beta were suppressed in neuronal cells from rat pheochromocytoma (PC12) cells with E(2). ERalpha cDNA transfected PC 12 cells elaborated more neurite-like processes with E(2). In clinics, we are currently preparing vaginal progesterone tablets, which essentially may concentrate in the endometrium to prevent endometrial cancer, with few general circulation of progesterone inviting less depression. The therapeutic effects of cyclic estrogen, such as its preventive effect, are suggested in these studies, at least on mild AD.

Alzheimer Disease↗

PubMedDate not supplied

Hyperintense signal of the posterior pituitary on T1-weighted MR images: an experimental study.

The origin of the hyperintense signal (HIS) of the pituitary gland posterior lobe (PL) on T1-weighted magnetic resonance (MR) images was investigated. Six rabbits were imaged on a 1.5 T device before and after 2 weeks' feeding of hypertonic saline solution (phase I). Two were killed soon after the second imaging; the pituitary gland was examined histochemically for neurosecretory granules containing antidiuretic hormone (ADH). The other four rabbits were given regular water for another 2 weeks (phase II) and then were again imaged. The plasma ADH level was monitored at each imaging session. In all subjects, the signal intensity of the PL decreased at the end of phase I, and the HIS reappeared at the end of phase II. The neurosecretory granules in the PL significantly diminished in number in phase I. Plasma ADH levels significantly increased in phase I and returned to their normal range in phase II. These clear correlations between MR findings and hormonal and histochemical results strongly suggest that the source of the HIS of the PL is the neurosecretory granules containing ADH.

Animals↗

PubMedDate not supplied

Effects of cGMP and cAMP on light responses of the photosensory pineal neurons in the lamprey, Lampetra japonica.

We examined in this study how external cyclic nucleotides affect the light response mechanism of the pineal photoreceptors and explored the existence of parietal eye type of photoreceptor of which the internal cGMP concentration increased during the light response. Pineal organs of river lampreys, Lampetra japonica, were treated with 8-bromo guanosine 3',5'-cyclic monophosphate (8Br-cGMP) or 8-bromo adenosine 3',5'-cyclic monophosphate (8Br-cAMP) before light stimuli, and the light responses were recorded from the second order neurons, chromatic or achromatic-type neurons. Excitatory and inhibitory light responses of the chromatic-type neuron became obscure by 9 and 3 mM 8Br-cGMP without changing the spontaneous spike discharge in the dark. 8Br-cAMP (3 mM) increased the frequency of spontaneous spike discharge, though it did not inhibit the light responses themselves. The inhibitory light response of the achromatic-type neuron decreased after adding 3 mM 8Br-cGMP, and it was unchanged by 3 mM 8Br-cAMP. The spontaneous spike discharge of the neurons in the dark was not affected by the cyclic nucleotides. The mechanism of these results can be explained if cGMP is an intracellular second messenger of light responses in the pineal photoreceptors and the blocking effect on photoresponses by externally applied 8Br-cGMP is caused by compensating for the reduction in intracellular cGMP by light. However, it does not indicate that the parietal eye type of photoreceptor found in lizard participates in the chromatic and achromatic-type responses in the lamprey pineal organ.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMedDate not supplied

Preparation and biopharmaceutical evaluation of microcapsules of amoxicillin.

Two methods of microencapsulation of amoxicillin, an orally administered antibiotic, were studied. One is based on dispersion of gelatin-amoxicillin mixture in liquid paraffin followed by drying and hardening with formalin-isopropanol treatment; the other is based on dispersion of ethylcellulose-amoxicillin mixture in purified water containing sodium lauryl benzene sulphonate. The microcapsules were recovered as discrete, free-flowing fine granules with a particle diameter of about 250-1000 microns. Dissolution of amoxicillin from ethylcellulose microcapsules was suppressed considerably with a zero-order dissolution pattern in solutions of various pH. Gastric-emptying-controlled rabbits were used for the in vivo evaluation of gelatin and ethylcellulose microcapsules. The ethylcellulose microcapsule containing 25 per cent amoxicillin showed a significantly sustained release pattern of amoxicillin. To establish a suitable design and for the evaluation of the sustained release microcapsules, a nomogram was made using pharmacokinetic parameters obtained after administration of a conventional formulation. It is advantageous for the preparation of sustained release microcapsules to chose pharmaceuticals having over about 2 as the ratio of the elimination rate constant, k10, to the release/absorption rate constant, kr, in the rabbit.

Absorption↗

PubMedDate not supplied

Eudragit RS and RL (acrylic resins) microcapsules as pH insensitive and sustained release preparations of ketoprofen.

Microencapsulation of ketoprofen using Eudragit RS and RL (acrylic resins) was investigated based on the dispersion system of ketoprofen-containing acetone in liquid paraffin. Aluminium tristearate was used as an additive for the preparation of microcapsules. Good reproducibility was observed in the microencapsulation and the resulting microcapsules were uniform, free-flowing particles. The phase diagram of ketoprofen-Eudragit RS or RL-aluminium tristearate indicated that it is only in a very limited region that spherical microcapsules ranging from 250 to 1000 microns in diameter could be prepared. Instrumental analysis using an energy dispersive-type X-ray microanalyser and a scanning electron microscope showed that aluminium tristearate was localized near the surface of the microcapsules. From these results, it was presumed that aluminium tristearate reduces the phase tension between Eudragit microcapsules and liquid paraffin. The dissolution patterns of ketoprofen from Eudragit RS and RL microcapsules were independent of the pH of the dissolution medium, and the dissolution rates were considerably lower than those from ketoprofen powders.

Acrylic Resins↗

PubMedDate not supplied

Eudragit E, L and S (acrylic resins) microcapsules as pH sensitive release preparations of ketoprofen.

Microencapsulation of ketoprofen using Eudragit E, L and S (acrylic resins) was investigated. The preparation is based on the dispersion of acetone containing ketoprofen in liquid paraffin. Aluminium tristearate was used as an additive for the preparation of microcapsules. In the preparation of microcapsules, the reproducibility of the Eudragit E microcapsule was better than that of Eudragit L and S microcapsules. The microcapsules obtained were uniform and free-flowing particles. From the phase diagram of ketoprofen-Eudragit E or S-aluminium tristearate, it became clear that the region in which the spherical microcapsules ranging from 250 to 1000 microns in size could be prepared was limited. The dissolution patterns of ketoprofen from Eudragit E, L and S microcapsules were dependent on the pH of the dissolution medium.

Acrylic Resins↗