Increase of striatal dopamine turnover by stress in MPTP-treated mice

The characteristics of motor function and brain dopamine (DA) metabolism in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice after immersion immobilization stress were investigated. There was no significant difference in locomotor activities between MPTP-treated and saline-treated mice, but locomotor activities of MPTP-treated mice after stress decreased more remarkably than those of saline-treated mice. Immediately after stress, striatal DA concentrations of MPTP-treated mice were significantly lower than those of saline-treated mice. Striatal DA levels improved when 24 h passed after stress. The striatal and cortical (DOPAC + HVA)/DA ratios of MPTP-and stress-treated mice was significantly higher than that of saline-and stress-treated mice. It is due to the decreased DA level and the enhancement of DA turnover that MPTP-treated mice became remarkably akinetic after stress, and that L-DOPA therapy is not effective when the symptoms in patients with Parkinson's disease worsen due to stress.     

Metabolism of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in blood--mainly in vitro]

Metabolism of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in blood was studied mainly in vitro. When 99mTc-ECD was mixed with blood taken from 12 subjects, the octanol extraction ratio of ECD (y) decreased rapidly and the octanol extraction ratio-time profile well fitted a monoexponential curve (y = Ae-kt/1000, A, k: constant, t: time after mixing). The k value and hematocrit (Ht) were significantly correlated (k = 0.376Ht-3.27, r = 0.897, p less than 0.001), therefore, it was suggested that the majority of the enzyme which dissolves ECD exists in red blood cells. When ECD was mixed with blood, there were more hydrophilic products of ECD in plasma than those generated by the enzyme in plasma. In vivo input function of 99mTc-ECD was calculated by arterial blood sampling and octanol extraction. The duration of effective input was relatively short, which was attributed to rapid decrease of octanol extraction ratio in vivo.     

Attenuated sympathetic tone augments nitrous oxide-induced myocardial depression during high-dose fentanyl anaesthesia in dogs

The purpose of this study was to determine whether centrally mediated sympathetic tone exerts compensatory effects on nitrous oxide-induced myocardial depression during high-dose fentanyl anaesthesia. The cardiovascular responses to 60 minutes of nitrous oxide administration after fentanyl, 100 micrograms.kg-1, were examined in 18 dogs with or without autonomic blockade induced by hexamethonium. Decreases of cardiac output and left ventricular stroke work were significantly greater in dogs with autonomic blockade (n = 9) by about 20 per cent of baseline values than in dogs without autonomic blockade (n = 9) at 30, 45, and 60 min. Similarly, left ventricular dP/dt was reduced more in dogs with autonomic blockade than in dogs without autonomic blockade, but this difference was only significant at the 60-min period. It is concluded that the sympathetic nervous system provides partial compensation for myocardial depression induced by nitrous oxide in the presence of high-dose fentanyl, suggesting that large doses of fentanyl do not ablate the centrally mediated sympathomimetic effects of nitrous oxide.     

Reduction of osteoclasts in a critical embryonic period is essential for inhibition of mouse tooth eruption.

Alveolar bone resorption by osteoclasts is essential for tooth eruption. Osteoclast-deficient Csfm(op) homozygous (op/op) mice, which lack functional macrophage colony-stimulating factor (M-CSF), suffer from osteopetrosis and completely lack tooth eruption. Although osteoclasts appear, and osteopetrosis is cured with age in op/op mice, tooth eruption is never seen. This fact suggests that there is a critical period when osteoclasts are required for tooth eruption. In this study, to detect the critical period, we administered an antagonistic antibody directed against c-Fms, a receptor for M-CSF, to inbred C57BL/6 mice for various periods. Administration of this antibody decreased tartrate-resistant acid phosphatase-positive (TRAP) osteoclasts, and incisor eruption was completely inhibited by continual administration of this antibody from embryonic day 15.5 (E15.5) until postnatal day 12.5 (D12.5). A 1-day delay of this administration abolished the inhibition of incisor eruption. The number of TRAP-positive osteoclasts was significantly reduced between E16.5 and E18.5 in the mice treated with antibody from E15.5 compared with those treated from E16.5. These results indicate that this period, during which the number of osteoclasts decreases significantly, is critical for inhibiting incisor eruption in C57BL/6 mice.     

Treatment of tardive dyskinesia with ceruletide

1. Seven patients with TD were treated with a single dose of ceruletide 0.8 microgram/kg i.m. 2. EMG and MV were recorded, and the average power spectrum was computed. 3. Effect of ceruletide on TD within 2 hr after injection was varied (3 cases: inhibitory, 2 cases: facilitatory, 2 cases: no effect). 4. Two patients with severe TD, who showed improvement after a single administration, received repeated administration of ceruletide (0.6 microgram/kg i.m.) and their TD symptoms were recorded on videotape for blind consensus ratings. In both patients ceruletide caused a marked decrease in severity of TD, and the effects lasted for several weeks. 5. The present findings might contribute to further understanding of the role of CCK in the brain and to the treatment of TD.     

Lack of modifying effects of atrazine and/or tamoxifen on thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN)

The modifying effects of atrazine, and/or tamoxifen, on thyroid carcinogenesis were investigated in a rat two-stage carcinogenesis model following N-bis(2-hydroxypropyl)nitrosamine (DHPN) initiation. Five-week-old male F344 rats were given a single subcutaneous injection of DHPN (2800 mg/kg, body weight) or vehicle alone. Starting 1 week later, the animals were fed a diet supplemented with 0, 5, 50 or 500 ppm of atrazine, 500 ppm atrazine plus 5 ppm tamoxifen, or 5 ppm tamoxifen in the DHPN-treated groups, and 0 or 500 ppm of atrazine in the DHPN-untreated groups for 24 weeks. At autopsy major organs, including the thyroid, pituitary, liver, kidney, testis, epididymis, and brain, were collected and histopathologically examined. Body weights were significantly (P<0.05) decreased by the high doses of atrazine or tamoxifen, the effect being enhanced in combination. Relative thyroid weights were significantly increased (P<0.05) only in the tamoxifen-treated group and pituitary weights were elevated with 500 ppm atrazine plus tamoxifen (P<0.05). Relative liver weights were increased by the high dose of atrazine. However, the atrazine and/or tamoxifen treatments did not induce significant histopathological changes in the major organs, including the thyroid, nor cause significant changes in serum TSH levels. These results suggest that neither atrazine nor tamoxifen may promote thyroid carcinogenesis, alone as well as in combination.     

Evaluating clinical educators: an employer's perspective

An Australian school of nursing's attempt to introduce an evaluation process required by management for clinical educators involved in undergraduate preregistration education is discussed Reliance on student feedback and clinical agencies' perceptions of the quality of teaching were seen as inadequate mechanisms for evaluation The evaluation process adopted incorporated observation of the educators together with self-reflection on their performance We conclude that post-briefings were poorly used and generally not reflective Educators relied heavily on their clinical skills and used a limited range of teaching strategies Whilst evaluation of clinical educators was time consuming and therefore costly, it is argued that it is essential to the integrity of the course The evaluation process has provided direction for support and development of clinical educators within the context of the curriculum     

Detection of beta-lactamase-producing strains isolated from urinary tract and their drug susceptibility

A total of 518 bacterial strains isolated from the urine of patients with various urological diseases in our Urological Department between November, 1987 and February, 1989 were studied for their beta-lactamase production and susceptibility to various antimicrobial agents was determined. beta-lactamase activity was determined by the acidometry disc method. There were 241 gram-positive cocci, 276 of gram-negative rods and 1 Neisseria gonorrhoeae. Thirty-four percent of the gram positive and 76.3% of gram negative rods produced beta-lactamase. S. aureus (81.3%), S. epidermidis (65.1%) in gram-positive cocci, E. cloacae (100%), S. marcescens (100%), C. freundii (100%), P. aeruginosa (97.2%), P. Rettgeri (88.9%), E. gergoviae (85.7%), K. oxytoca (84.6%), M. morganii (81.8%) and E. coli (69.0%) in gram-negative rods produced beta-lactamase at a higher rate. beta-lactamase produced by gram-positive cocci was entirely penicillinase, and that produced by gram-negative rods only penicillinase in 4.0%, only cephalosporinase in 44.2% and both in 25.4%. In S. aureus and S. epidermidis, the isolated rate of strains resistant to ampicillin (p less than 0.01) and piperacillin (p less than 0.05) in the beta-lactamase producing strains was significantly higher than that in the beta-lactamase non-producing strains. In E. coli, the isolation rate of strains resistant to ampicillin and piperacillin in the penicillinase-producing strains was significantly higher than in the penicillinase non-producing strains (p less than 0.01). But both cephalosporinase-producing strains and beta-lactamase non-producing strains showed high susceptibility to cephalothin. These results suggest that the penicillinase might present a clinical problem in the treatment of urinary tract infections by S. aureus, S. epidermidis and E. coli.