Conserved and novel structural characteristics of enantiomorphic Leu-enkephalin

The crystal of the Leu-enkephalin raceinate (L-Tyr-Gly-Gly-L-Phe-L-Leu and d -Tyr-Gly-Gly-D-Phe-D-Leu) was obtained as a centrosymmetric space group. Crystal data: C₂₈H₃₇N₅O₇· 1.5H₂O, M_w, = 582.6, triclinic, space group PI, a = 11.176(3), b = 16.115(3), c = 10.204(4) Å, α= 92.41(3), β= 104.86(2), γ= 85.35(2) °, V= 1770(1) ų, Z= 2; F(000) = 640, μ(CuKα) = 6.50 cm^?1, D_x= 1.081 g cm^?3. The structure was determined by X-ray diffraction. The conformation of the Leu-enkephalin racemate was classified into the extended form which has been often observed in natural enkephalin. The symmetry-related molecules were connected by hydrogen bonds and arranged in an antiparallel fashion. The molecular packing showed a sheet structure similar to that of natural enkephalin.     

Toxicity and Teratogenicity Studies with the Hypolipidemic Drug RMI 14,514 in Rats

Toxicity and Teratogenicity Studies with the Hypolipidemic DrugRMI 14,514 in Rats. Gibson, J.P., Larson, E.J.^A, Yarrington,J.T., Hook, R.H., Kariya, T. and Blohm, T.R. (1981 ).Fundam.Appl.Toxicol. 1:19–25. The hypolipidemic drug RMI 14,514 (5-tetradecyloxy-2-furoicacid) has an oral LD50 of over 5000 mg/kg in rats. In a chronictoxicity study (6 months drug diet) doses of 30,100, or 300mg/kg/day produced no obvious signs of toxicity or abnormalclinical pathology parameters, other than prominent growth retardationat 300 mg/ kg, which was somewhat alleviated when the dose wasreduced to 200 mg/kg after 6 weeks. Hepatic change in the formof mild lipid accumulation was noted histopathologically after6 months of treatment at 100 or 300 mg/kg/day, but was not presentat 3 months or after 4 weeks off drug. The administration ofRMI 14,514 in the diet to pregnant rats at 30, 100, or 150 mg/kg/dayon Days 7 thru 21 of pregnancy (day 1 = day sperm detected)did not induce any teratogenic effects. When rats were exposedto the drug from implantation thru sexual maturity (126 daysof age) at the same dosage, it produced no adverse developmentalor behavioral effects, except for slight reduction in weightgain from birth to sexual maturity at 150 mg/kg/day. The drugcaused reductions in plasma cholesterol and total fatty acids,but no distinct changes in various tissue lipids, except inthe erythrocyte where fatty acids and phospholipids were reduced.These differences did not affect membrane integrity of the erythrocyteas far as osmotic or mechanical fragility tests could determine.The drug, which bears a structural resemblance to long-chainfatty acids, was incorporated into tissue lipids in detectableamounts, but tended to disappear from tissues at a rate similarto that of expected lipid turnover after treatment was stopped.     

Antagonistic Effects of OPC-14597, a Novel Antipsychotic Drug,on Quinpirole- and (–)-Sulpiride-induced Changes in Evoked Dopamine Release in Rat Striatal Slices

The effects of a newly synthesized quinolinone derivative, 7-{4-(4-(2,3-dichlorophenyl)-1-piperazinyl) butoxy}-3,4-dihydro-2-(1H)-quinolinone (OPC-14597), a novel antipsychotic drug, on electrically evoked dopamine release in rat striatal slices were investigated. OPC-14597 (0.1–10 μm) had no effect on the dopamine release evoked in the striatal slices. The decrease induced by quinpirole, a dopamine receptor agonist, in evoked dopamine release was attenuated by supervision with OPC-14597 (1 and 10 μm) which by itself had no effect on evoked dopamine release. The increase induced by (–)-sulpiride, a dopamine receptor antagonist, in evoked dopamine release was, moreover, also attenuated by 1 and 10 μm OPC-14597. These findings indicate that OPC-14597 antagonizes both dopamine agonist- and antagonist-induced changes in evoked dopamine release in striatal slices in rats.     

Strain difference in behavioral response to a new environment in rats

Abstract Locomotor activity in rats throughout a 24-hour period in a new environment was examined for strain differences and for the capacity for adaptation to that environment. Fischer 344 rats (F344), spontaneously hypertensive rats (SHR) and Wistar normotensive Kyoto rats (WKY) were used. The horizontal locomotor activity of individual rats was measured by photocell-utilizing activity-recording devices. The locomotor activity counts on the second day, after 1 day of adaptation, were compared with those after 5 days of adaptation (on the sixth day). In WKY, there was no difference in activity at any period of the day between the second and sixth days. In SHR, the locomotor activity on the second day between 6:00 h and 9:00 h (in the light phase) and between 24:00 h and 3:00 h (in the dark phase) was higher than on the sixth day. In F344, the locomotor activity on the second day between 18:00 h and 2:00 h was higher than on the sixth day. The capacity for adaptation in SHR and F344 was thus poorer than in WKY. The poor adaptation in SHR and F344 was similar to that in depressive patients induced by moving house. These findings suggested that SHR or F344 were suitable for depression research.     

Increased cyclooxygenase-2 expression is correlated with suppressed antitumor immunity in cervical adenocarcinomas

Cyclooxygenase-2 (COX-2) inhibition suppressed the growth of various tumors. The augmentation of antitumor immunity by increasing cytotoxic lymphocytes may be an important mechanism for COX-2 inhibition. Among cervical cancers, adenocarcinomas present more aggressive behavior and overexpressed COX-2. The expression of COX-2 and the CD8+ lymphocyte infiltrations were evaluated in this study by immunohistochemistry. We studied COX-2 expression and CD8+ lymphocyte infiltration in 55 women with cervical adenocarcinomas. COX-2 expression and tumor stromal CD8+ lymphocytes were evaluated by semiquantified methods. Tumor intraepithelial lymphocytes were counted under microscopic field of x200. Correlations between these data and other clinicopathologic features were investigated. Thirty-seven out of 55 (67.3%) cervical adenocarcinomas significantly expressed COX-2. Patients who died within 5 years showed higher percentage of COX-2 expression than survivors (100% vs 58.1%, P < 0.05). Victims also showed lesser intraepithelial CD8+ lymphocyte counts than survived patients (3.4 vs 26.4, P < 0.05). COX-2 expression and tumor intraepithelial lymphocyte count were reversely correlated with each other (correlation index: -0.38, P < 0.01). Up-regulated COX-2 expression and lesser tumor intraepithelial CD8+ lymphocyte count are poor prognostic indicators for cervical adenocarcinoma patients. COX-2 may play an important role in the suppression of host antitumor immunity in cervical adenocarcinomas.     

White blood cell count,C-reactive protein and erythrocyte sedimentation rate in respiratory syncytial virus infection of the lower respiratory tract

Laboratory findings such as white blood cell (WBC) count, C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) level in patients with bronchiolitis, bronchopneumonia and lobar pneumonia caused by respiratory syncytial virus (RSV) were studied. The diagnosis of having RSV infection of the lower respiratory tract was made on the presence of RSV antigen in nasopharyngeal specimens by means of enzyme immunoassay, on chest X-ray appearances and clinical manifestations. The WBC counts in the lobar pneumonia cases (n = 25, 12 288 ± 6296/mm³) were significantly greater than those for the bronchiolitis (n = 52, 9562 ± 2720/mm³) and bronchopneumonia (n = 43, 8369 ± 3714/mm³) cases. The concentrations of CRP in lobar pneumonia cases (n = 25, 6.5 ± 7.3 mg/dL) were significantly greater than those in the bronchiolitis (n = 52, 1.9 ± 2.0 mg/dL) and bronchopneumonia (n = 43, 2.1 ± 2.4 mg/dL) cases. The ESR levels in the lobar pneumonia cases (n = 24, 43.8 ± 29. mm/h) were also significantly higher than those in the bronchiolitis (n = 34, 20.1 ± 12.3 mm/h) and bronchopneumonia (n = 40, 24.7 ± 15.9 mm/h) cases. There were no significant differences in the WBC counts, the CRP concentrations and ESR levels between the bronchiolitis and bronchopneumonia cases. These results suggest that the RSV lobar pneumonia cases are coinfected with some bacterial organisms more heavily than in the RSV bronchiolitis and bronchopneumonia cases.     

Lingual cyst in infancy: Importance of palpation for diagnosis

Two infants, 5 and 12 weeks of age, with lingual cysts were presented. Histological findings were compatible with a salivary retention cyst in one and a thyroglossal duct cyst in the other. Both infants were admitted to our hospital because of severe stridor that had developed from one to two weeks of age. Their lingual cysts were easily recognizable by simple palpation and were confirmed by non-invasive imaging techniques, such as ultrasound sonography, computed tomography and magnetic resonance imaging. Lingual cyst in infancy may be large enough to cause stridor and dyspnea, and occasionally result in sudden infant death, although once diagnosis is made a radical operation can be easily performed. Therefore, it is important that palpation in the oral cavity should be performed with all infants with persistent stridor as a part of a physical examination.