Novel retinoid X receptor antagonists: specific inhibition of retinoid synergism in RXR-RAR heterodimer actions

Several 2-(arylamino)pyrimidine-5-carboxylic acids were designed as novel retinoid X receptor (RXR) antagonists. Compound 6a or 6b alone did not exhibit differentiation-inducing activity toward HL-60 cells and did not affect the activity of a retinoic acid receptor (RAR) agonist, Am80, but did inhibit the synergistic activity of an RXR agonist, PA024 (3), in the presence of Am80. The activity of 6 was ascribed to selective antagonism at the RXR site of RXR-RAR heterodimers.     

Neuritogenesis of herbal (+)- and (-)-syringaresinols separated by chiral HPLC in PC12h and Neuro2a cells

Syringaresinol isolated from Epimedium koreanum NAKA1 and Magnolia officinalis REHD. et WILS. was subjected to optical resolution by chiral HPLC to give (+)- and (-)-enantiomers. The two syringaresinol enantiomers, as well as a mixture of their glucosides, showed dose-dependent neuritogenesis in a concentration range from 0.24 to 24 microM in PC12h cells.     

Psychiatric disorders among patients undergoing hemodialysis therapy

We examined the incidence rates of psychiatric disorders in end-stage renal failure patients on hemodialysis (HD) based on 4-year long-term follow-up. Among various psychiatric disorders, the frequency of three psychiatric disorders, dementia, delirium, and major depression, was relatively high. One-year incidence rate of whole psychiatric disorders was 10.6% (7.1% in non-aged and 13.7% in aged). One-year incidence rate of dementia in aged patients was 4.2% (dementia of the Alzheimer's disease, 0.5%; multi-infarct dementia, 3.7%). One-year incidence rate of multi-infarct dementia in aged HD patients was 7.4 times as large as that in the elderly general populations, suggesting that aged HD patients tend to exhibit multi-infarct dementia. The high incidence rate may be closely related to advanced arteriosclerosis and other medical conditions. Psychiatric management is required for ESRD patients with three major psychiatric disorders, dementia, delirium, and major depression, in particular for aged patients with multi-infarct dementia who has received long-term HD therapy.     

The preventive effect of allopurinol spray on stomatitis induced by anti-cancer drugs

The present study was conducted to evaluate the effect of allopurinol spray on stomatitis induced by chemotherapy for esophageal cancer. The chemotherapeutics used consisted of 5-FU + CDDP (FC) given to 40 patients and 5-FU + ND (FN) given to 9 patients. Allopurinol solution for spray was prepared using a gelatin agent as base. The allopurinol spray was used 3-5 times daily before and after chemotherapy. The Japan Society for Cancer Therapy's criteria for stomatitis were used. With FN-therapy, no stomatitis was observed. With FC-therapy, 9 of 40 patients developed stomatitis of grade 1 (8 patients) or grade 2 (1). The incidence of stomatitis was 18.4% with all therapies and 22.5% with FC-therapy. The average graded toxicity was 0.20 for all therapies and 0.25 for FC-therapy. These results suggest that allopurinol spray is markedly effective for the prevention of stomatitis induced by chemotherapy. In addition, allopurinol spray is portable and convenient, and resulted in less nausea or vomiting than mouthwash.     

Production of Multiple Growth Factors by a Newly Established Human Thyroid Carcinoma Cell Line

A multiple growth factor-producing tumor cell line (NIM-1) was newly established from a patient with thyroid cancer and remarkable neutrophilia. NIM-1 cells also caused severe neutrophilia in nude mice bearing tumors. NIM-1-conditioned medium (NIM-1CM) contained activities that supported not only granulocyte, macrophage and eosinophil colony formation of human bone marrow cells but also the growth of colony-stimulating factor (CSF)-dependent cell lines, NFS60-KX and TF-1. Northern blot hybridization analysis revealed the constitutive expression of granulocyte-CSF (G-CSF), granulocyte/macrophage-CSF (GM-CSF) and interleukin(IL)-6 mRNAs in NIM-1 cells. Enzyme-linked immunosorbent assays (ELISA) using NIM-1CM also confirmed the production of IL-la and a small amount of IL-1β besides G-CSF, GM-CSF and IL-6 in NIM-1 cells. In addition, unexpected production of IL-11 in NIM-1 cells was detected by northern blot hybridization analysis and by bioassay using an IL-11-dependent cell line. Therefore, NIM-1 cell line is shown to produce multiple cytokines including potentially megakaryopoietic growth factors such as GM-CSF, IL-6 and IL-11.     

Liver injuries induced by cyclochlorotine isolated from Penicillium islandicum

Sequential morphological changes in murine liver induced by cyclochlorotine (CC), a secondary metabolite of Pencicillium islandicum were investigated by transmission electron microscopy and scanning electron microscopy. Within 15 min after the administration of CC there was a marked dilatation of Disse's space around the portal triads, and the exudates then poured out into the space which was formed by the invagination of the hepatocyte plasma membrane. Shortly after the invagination was completed, the connection between Disse's space and the invaginated space was pinched off, so that this space became a membrane-bound vacuole. After dehydration, the vacuoles became granular. The liver injuries induced by CC were influenced by various pretreatments. The results indicate that drug-metabolizing systems mediated by cytochrome p-450 in the hepatocytes may play an important role in the hepatotoxicity of CC.     

Influence of cigarette smoke on the L-ascorbic acid metabolism and the activities of drug-metabolizing enzyme in rats

This study clarified the influence of cigarette smoke on the L-ascorbic acid (AsA) metabolism and the activities of drug-metabolizing enzyme in rats. The test rats (group T) were exposed to weak sidestream smoke from cigarettes for 2 h, everyday for 57 days. AsA concentration in the tissues and excreted amount of AsA in urine of group T tended to be higher than those of control group (group C). The plasma AsA concentration and the activities of aniline hydroxylase and 7-ethoxycoumarin O-deethylase of group T were significantly higher than those of group C. There was no significant difference in the activity of UDP glucuronosyltransferase or in the liver cytochrome P-450 content between these two groups.     

Surgical anatomy of the cervical carotid artery for carotid endarterectomy

Carotid endarterectomy (CEA) is the main treatment for atherosclerotic plaque of the cervical internal carotid artery. The surgical anatomy of the carotid arteries was studied in the carotid triangle of 49 cadavers. The carotid bifurcation was located at the level of the lower third of C-3. The superior thyroid artery arose from the anterior wall of the external carotid artery in 70% of specimens and from the distal portion of the common carotid artery in 30%. The lingual artery arose as a separate trunk between the origins of the superior thyroid and facial arteries in 81% of specimens, with the facial artery from a common trunk in 18%, and with the superior thyroid artery in 1%. The occipital artery arose from the posterior aspect of the external carotid artery above the level of origin of the facial artery in 57% of specimens, between the origins of the facial and lingual arteries in 32%, and below the origin of the lingual artery in 11%. The origin of the occipital artery was positioned low and the distal portion of the occipital artery was crossed by the hypoglossal nerve in 20%. The ascending pharyngeal artery arose from the posterior wall of the external carotid artery above the level of origin of the lingual artery in 66% of specimens, below the origin of the lingual artery in 9%, from the proximal portion of the occipital artery in 19%, from the carotid bifurcation in 2%, and from the internal carotid artery in 2%. The branches of the external carotid artery are the key landmarks for adequate exposure and appropriate placement of cross-clamps on the carotid arteries. It is necessary to understand the surgical anatomy of the carotid arteries to carry out successful removal of plaque and minimize postoperative complications in a bloodless surgical field.