Anti-aggressive effects of agonists at 5-HT1B receptors in the dorsal raphe nucleus of mice

Rationale In rodents, serotonin 1B (5-HT_1B) agonists specifically reduce aggressive behaviors, including several forms of escalated aggression. One form of escalated aggression is seen in mice that seek the opportunity to attack another mouse by accelerating their responding during a fixed interval (FI) schedule. Responses preceding the opportunity to attack may reflect aggressive motivation. Objective This study investigated the effects of two 5-HT_1B receptor agonists on the motivation to fight and the performance of heightened aggression. Materials and methods Male mice were housed as “residents” and performed nose-poke responses on an FI 10-min schedule with the opportunity to briefly attack an “intruder” serving as the reinforcer. In the first experiment, the 5-HT_1B receptor agonist, CP-94,253 (0–10 mg/kg, IP), was given 30 min before the FI 10 schedule. To confirm that CP-94,253 achieved its effects via 5-HT_1B receptors, the 5HT_1B/1D receptor antagonist, GR 127935 (10 mg/kg, IP) was administrated before the agonist injection. In the second experiment, the 5-HT_1B agonist CP-93,129 (0–1.0 μg) was microinjected into the dorsal raphe 10 min before the FI 10 schedule. Results The agonists had similar effects on all behaviors. CP-94,253 and CP-93,129 significantly reduced the escalated aggression towards the intruder at doses lower than those required to affect operant responding. The highest doses of CP-94,253 (10 mg/kg) and CP-93,129 (1.0 μg) decreased the rate and accelerating pattern of responding during the FI 10 schedule; lower doses were less effective. GR 127935 antagonized CP-94,253’s effects on all other behaviors, except response rate. Conclusions These data extend the anti-aggressive effects of 5-HT_1B agonists to a type of escalated aggression that is rewarding and further suggest that these effects are associated with actions at 5-HT_1B receptors in the dorsal raphe.     

Mechanical accuracy of a stereotactic irradiation system using a micro multi-leaf collimator

Mechanical accuracy of a stereotactic irradiation system using a micro multi-leaf collimator (mMLC), Elekta DMLC, has been evaluated. Measurements were made to obtain transmission, leakage, penumbra, and positioning accuracy of the DMLC leaf for a 6 MV photon beam. Mechanical accuracy and long term stability of a linac isocenter was also evaluated. The resulting transmission, along a line perpendicular to the leaf movement, was 0.31±0.01%, and the leakage from the closed opposing leaf pairs was 0.39±0.01%. The measured penumbra, at a depth incurring maximum dose, was 2.37±0.16 mm toward the leaf end and 2.14±0.18 mm toward the leaf side for various field sizes. The leaf gap width error, of 0.10±0.08 mm, was obtained by analyzing picket fence test results. The maximum leaf positioning error, of 0.14±0.06 mm, was obtained by analyzing the log file for a various gantry angles during an arc delivery. The isocenter accuracy was within a radius of 1 mm, without any recalibration for two years. In conclusion, our stereotactic irradiation system using DMLC was capable of providing accurate stereotactic treatment.     

beta-Cryptoxanthin, a novel natural RAR ligand, induces ATP-binding cassette transporters in macrophages

Despite its serious adverse effects, recent accumulating evidence suggests that a physiological retinoic acid receptor (RAR) agonist, all-trans retinoic acid (atRA), exhibits preventive effects on atherogenesis. Therefore, the present study was designed to explore novel natural RAR ligands with anti-atherogenic effects in order to identify and develop a drug without severe side effects. Among xanthophylls and carotenoids studied, beta-cryptoxanthin and lutein exhibited RAR ligand activity in yeast two-hybrid system that was found to be completely abolished by the RAR pan-antagonist LE540. Furthermore, these molecules can bind the RAR ligand-binding domain in the CoA-BAP system but not RXR ligand-binding domain. These results indicate that both beta-cryptoxanthin and lutein serve as ligands for RAR, but not RXR, although their binding affinity was three orders of magnitude lower than that of atRA. Additionally, when applied to macrophages, beta-cryptoxanthin indeed was found to induce the ATP-binding cassette transporter A1 (ABCA1) and ABCG1 mRNAs, which exert anti-atherosclerotic effects by preventing cholesteryl ester accumulation in macrophages. The induction of ABCA1 proteins by beta-cryptoxanthin as well as atRA was abrogated by LE540. In summary, beta-cryptoxanthin appears to be more an efficient provitamin A source than other carotenoids and xanthophylls including beta-carotene, since beta-cryptoxanthin can act not only as a RAR agonist but also a source of vitamin A. Taking into account that the pharmacodynamics difference between beta-cryptoxanthin and atRA, beta-cryptoxanthin appears to exert beneficial effects on atherogenesis through RAR activation in the manner different from atRA.     

Mitral valve replacement in children under 3 years of age

Objective: This study was undertaken to review our experience of mitral valve replacement in children under 3 years of age. Methods: Between January 1990 and May 2004,18 patients under 3 years of age underwent a total of 20 mitral valve replacements using a bileaflet mechanical prosthetic valve. There were 9 males and 11 females. The age at surgery ranged from 3 months to 3 (mean=1.02±0.72) years and body weight varied between 3.4 and 13.2 (mean=7.08±2.74) kg. Results: There were 4 early and 2 late deaths, and these occurred in severe cases aged less than 1 year of age. Re-replacement of mitral valve was required in 3 patients (valve thrombosis in 2 and pannnus formation in 1). Orifice size of the implanted prosthesis (OS) as compared with the predicted normal size of the mitral valve (NS) was well correlated with maximum transprosthetic flow velocity estimated by Doppler echocardiography. In this study, the OS/NS>0.65 was maintained in all patients, and none required re-replacement because of prosthesis-patient mismatch. Conclusion: Patients less than 1 year of age had significant mortality and morbidity. The results were satisfactory in the remainder (1–3 years). During this follow-up period, none required re-replacement due to somatic growth, but it will be an unavoidable problem in the future. The OS/NS, which can be checked with a regular physical examination, may serve as a guide to determine the most appropriate timing for the second surgery.     

The characteristics of coronary artery revascularization in aged patients

This study was undertaken in order to clarify the clinical characteristic features and surgical results of coronary artery bypass grafting (CABG) in patients over 65 years of age (group III, n=43). These patients were compared with 2 other groups of patients, one aged between 50 and 59 years (group I, n=88) and another aged between 60 and 64 years (group II, n=54), with respect to mortality, morbidity and late survival. CABG was performed with the saphenous vein under cold K-Mg-cardioplegia with systemic hypothermia. The hospital mortality was 2.3, 3.7, and 4.7 per cent in groups I, II and III, respectively, although no operative mortality was noted in any group. The number of coronary artery lesions increased with age, however, the left ventricular ejection fraction was relatively better preserved in the aged patient than in the younger ones. The 5-year survival rates were 93.4, 95.1 and 96.9 per cent in groups I, II and III, respectively, with most of the late deaths occurring within a year after CABG in each group. In the aged patients, postoperative functional recovery was delayed in the liver and kidney, and postoperative psychosis was not infrequent. The results of this study, indicating a low operative mortality and satisfactory late survival rate, thus strongly support CABG for the aged. Nevertheless, the prevention of postoperative complications is also extremely important for reducing hospital mortality.     

Transplantation of telencephalic neural progenitors induced from embryonic stem cells into subacute phase of focal cerebral ischemia

Cerebral ischemia causes neuronal death and disruption of neural circuits in the central nervous system. Various neurological disorders caused by cerebral infarction can severely impair quality of life and are potentially fatal. Functional recovery in the chronic stage mainly depends on physical treatment and rehabilitation. We aim to establish cell therapy for cerebral ischemia using embryonic stem (ES) cells, which have self-renewing and pluripotent capacities. We previously reported that the transplanted monkey and mouse ES cell-derived neural progenitors, by stromal cell-derived inducing activity method, could survive and differentiate into various types of neurons and glial cells, and form the neuronal network in basal ganglia. In this report, we induced the differentiation of the neural progenitors from mouse ES cells using the serum-free suspension culture method and confirmed the expression of various basal ganglial neuronal markers and neurotransmitter-related markers both in vitro and in vivo, which was thought to be suitable for replacing damaged striatum after middle cerebral artery occlusion. This is the first report that used selectively induced telencephalic neural progenitors into ischemia model. Furthermore, we purified the progenitors expressing the neural progenitor marker Sox1 by fluorescence-activated cell sorting and Sox1-positive neural progenitors prevented tumor formation in ischemic brain for 2 months. We also analyzed survival and differentiation of transplanted cells and functional recovery from ischemic damage.     

The Complete Nucleotide Sequence of the PanAsia Strain of Foot-and-Mouth Disease Virus Isolated in Japan

The complete nucleotide sequence of the foot-and-mouth disease virus (FMDV) O/JPN/2000 strain, the PanAsia strain, was determined by cycle sequencing and primer walking. The 5 end of the genome upstream from homopolymeric poly(C) tract (S-fragment) was 367 nucleotides in length, and the remainder of the genome (L-fragment), excepting the poly(A) tail, was 7808 nucleotides. The L-fragment contains a single open reading frame of 6996 nucleotides terminating at a UAA codon 96 bases from the 3 poly(A) sequence. Comparison of sequences shows that the length of the structural and non-structural protein coding regions are identical to those in the O1/Kaufbeuren strain, and no striking differences such as deletion or insertion were observed between them.     

Impact of detection of bacterial endotoxin in menstrual effluent on the pregnancy rate in in vitro fertilization and embryo transfer

OBJECTIVE: To examine whether bacterial endotoxin is detectable in menstrual effluent and to analyze a possible association between endotoxin levels and a pregnancy rate after IVF-ET. DESIGN: Prospective observational study. SETTING: University hospital. PATIENT(S): Thirty-eight infertile women undergoing endotoxin assay and IVF-ET. INTERVENTION(S): Endotoxin was assayed by the limulus amoebocyte lysate test. MAIN OUTCOME MEASURE(S): Levels of bacterial endotoxin and a pregnancy rate. RESULT(S): In 38 samples of menstrual effluent taken from 38 women, bacterial endotoxin was detected with a range of 7.1 to >1,000 pg/mL in 37 samples and was not detected in 1 sample. After IVF-ET, pregnancy occurred in 9 of the 38 women. The mean (+/- SD) endotoxin level in these 9 pregnant women was 71.3 +/- 52.5 pg/mL and was significantly lower compared with >236.2 +/- 333.6 pg/mL in the 29 nonpregnant women. All pregnancies occurred in 28 women with an endotoxin level of 200 pg/mL, producing the significantly higher pregnancy rate in the former group than in the latter. CONCLUSION(S): Bacterial endotoxin was detectable in menstrual effluent from infertile women. The pregnancy rate after IVF-ET was significantly higher in women with an endotoxin level of 200.0 pg/mL.