Antinociceptive Effects of Morphine Were Different Between Experimental and Genetic Diabetes

This study was designed to investigate the effect of morphine on formalin-induced nociceptive responses in streptozotocin (STZ) induced-diabetic mice, noninsulin-dependent genetically diabetic db/db mice and their respective controls (ddY and +/+). In nondiabetic (ddY and +/+) mice, morphine (1–10 mg/kg, PO) dose dependently attenuated the biphasic nociceptive responses induced by SC injection of formalin to the hindpaw, demonstrating equipotency on both the first and second phases. Para-chlorophenylalanine (800 mg/kg × 2, PO) and pindolol (1 mg/kg, IP) reduced the effect of morphine on the first phase, sulpiride (10 mg/kg, IP) abolished the effect on both phases, while ketanserin (1 mg/kg, IP) had no effect. In STZ (200 mg/kg, IP)-diabetic mice, morphine weakly attenuated the nociception in comparison to control ddY mice, whereas it had comparable effects in both the first and second phases of control +/+ mice and db/db mice. The serotonergic agonist, meta-chlorophenylpiperazine (0.32–3.2 mg/kg, PO), dose dependently attenuated the biphasic nociceptive responses to formalin in both phases of diabetic mice; however, FR64822, a dopaminergic compound (0.1–10 mg/kg, PO), had little effect. We speculate that activation of both dopaminergic (DA)- and serotonergic-mediated mechanisms are potentially responsible for the effect of morphine on the first phase, while the DA-mediated effect is involved in the second phase. The DA-mediated mechanism, but not the serotonin-mediated one, appears to be altered in both STZ-diabetic and db/db mice. These results suggest that the attenuated effects of morphine might be due to a dopaminergic dysfunction in STZ mice, and that there might be other mechanisms compensating for this attenuation of dopaminergic function in db/db mice.     

Testing for skin sensitization according to the notification procedure for new chemicals: the Magnusson and Kligman test

The notification procedure for new chemicals in the European Union (called the Chemicals Act in Germany) requires a skin sensitization test when the amount of a new chemical produced exceeds 100 kg/year. The preferred test is that of Magnusson and Kligman; more than 90% of the tests submitted are performed with it. Though the Magnusson and Kligman test is described in the literature, and in the test guidelines of the European Union and of the OECD, discrepancies do occur in the performance of the test between test laboratories. In this paper, recommendations are given for standardized performance of the Magnusson and Kligman test.     

间餐与中学生脑力工作能力关系研究

为阐明课间加餐对中学生上午学习能力的影响，采用剂量作业试验，通过自身前后对比，分析了间餐与脑力工作能力的关系，结果表明间餐不仅加快了脑力工作速度，控制了末节课的错误率，而且较有效地降低了显著疲劳发生率，经ｌｏｇｉｓｔｉｃ逐步回归分析，显示间餐及高质量早餐均为阻遏疲劳发生之保护因子。     

ACEA-1328, AN NMDA RECEPTOR ANTAGONIST, INCREASES THE POTENCY OF MORPHINE AND U50,488H IN THE TAIL FLICK TEST IN MICE

The effect of 5-nitro-6,7-dimethyl-1,4-dihydro-2,3-quinoxalinedione (ACEA-1328), a competitive and systemically bioavailable NMDA receptor/glycine site antagonist, was examined on opioid-induced antinociception in the tail flick test. Swiss Webster mice were injected with ACEA-1328 either alone or in combination with morphine or (±)-trans-U-50488 methanesulfonate (U50,488H), a μ- and a κ-opioid receptor agonist, respectively, and tested for antinociception. Systemic administration of ACEA-1328 alone increased the tail flick latencies with an ED₅₀of approximately 45 mg kg⁻¹. Concurrent administration of ACEA-1328 with morphine, or U50,488H, at doses that did not affect tail flick latencies, potentiated the antinociceptive effect of the opioid analgesics and vice versa. Naloxone, an opioid receptor antagonist, while not modifying the effect of ACEA-1328, did block the augmentation, suggesting that opioid receptors might be involved in the latter effect. 5-Aza-7-chloro-4-hydroxy-3-(m-phenoxyphenyl)quinoline-2(1H)-one (ACEA-0762), a selective NMDA receptor/glycine site antagonist, also showed enhancement of the antinociceptive effect of morphine and U50,488H. However, concurrent administration of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX), a selective non-NMDA receptor antagonist, with morphine did not alter the antinociceptive potency of the opioid analgesic. Overall, the data suggest that ACEA-1328 may increase the potency of the opioid analgesics by antagonising the glycine site associated with the NMDA receptor.     

Pineal response after pyridoxine test in children

Summary To characterize the pineal response to pyridoxine, plasma melatonin was measured in one hundred and twenty children 3 hours after vitamin B₆ administration. The children, aged between 1.5 and 8 years, were divided in four groups as follows: a) control day group, grouping 27 children sampled at 9:00 and at 12:00; b) control night group, grouping 29 children sampled at 21:00 and at 24:00; c) pyridoxine day group, grouping 30 children sampled at 9:00, then intravenously (i.v.) injected with 3mg/kg of pyridoxine, and sampled at 12:00; and d) pyridoxine night group, grouping 34 children sampled at 21:00, i.v. injected with 3mg/kg of pyridoxine, and sampled at 24:00. Melatonin concentration was measured by radioimmuno assay. The data obtained showed a significant increase in melatonin levels after pyridoxine administration in the pyridoxine night group (39.87 ± 8.02pg/ml basal vs 88.45 ± 9.21 pg/ml after pyridoxine, p < 0.001). The other groups did not showed significant differences in melatonin concentrations. Statistical analysis shows that the administration of pyridoxine during the nocturnal hours represents a stimulating factor to increase the pineal production of melatonin in children.     

Comparison of mathematically determined blood lactate and heart rate “threshold” points and relationship with performance

Summary The purpose of this study was to investigate the relationship between threshold points for heart rate ( ) and blood lactate (Th_1a) as determined by two objective mathematical models. The models used were the mono-segmental exponential (EXP) model of Hughson et al. and the log-log (LOG) model of Beaver et al. Inter-correlations of these threshold points and correlations with performance were also studied. Seventeen elite runners (mean, SD = 27.5, 6.5 years; 1.73, 0.05 m; 63.8, 7.3 kg; and maximum oxygen consumption of 67.8, 3.7 ml · kg^–1 · min^–1) performed two maximal multistage running field tests on a 183.9-m indoor track with inclined turns. The initial speed of 9 km · h^–1 (2.5 m · s^–1) was increased by 0.5 km · h^–1 (0.14 m · s^–1) every lap for thef _c test and by 1 km · h^–1 (0.28 m · s^–1) every 4 min for the la test. After fitting the la or thef _c data to the two mathematical models, the threshold speed was assessed in the LOG model from the intersection of the two linear segments (LOG-1a; LOG-f _c) and in the EXP model from a tangent point (TI-1a; TI-f _c). Th_1a and speeds computed with the two models were significantly different (P<0.001) and poorly correlated (LOG-1a vs LOG-f _c:r=0.36, TI-1a vs TI-f _c:r=0.13). In general, were less well correlated with performance than Th_1a. With two different objective mathematical models, this study has shown significant differences and poor correlations between Th_1a and . Thus thef _c inflection point with Conconi's protocol is a poor indicator of the la breakpoint with a conventional multistage protocol and a weaker indicator of running performance.     

EFFECTS OF ACUTE AND CHRONIC ADMINISTRATION OF TWO ANTIBIOTICS, AZTREONAM AND GENTAMICIN, ALONE OR IN COMBINATION, ON "OPEN-FIELD TEST" IN MICE

A study aimed at investigating the behavioural effects of aztreonam and gentamicin, given separately or in combination, was carried out in mice. Animals were randomly assigned to two test conditions: acute and chronic treatment. Those receiving acute treatment had a single IP injection 60 min before the test. Those receiving chronic treatment had IP injections once daily for 5 successive days prior to the test. Behavioural patterns (ambulation, rearing, grooming and defecation) were assessed using the "open-field" test. The results indicate that, both after single and multiple dosing, aztreonam (10, 40 and 80 mg/kg IP) and/or gentamicin (10 mg/kg IP) do produce changes in the behaviour of animals. A rate increasing effect for certain behaviours (rearing, grooming and defecation) and a reduction in other behaviours (ambulation) seems to occur.     

呼出气氢测定试验对飞行人员乳糖酶缺乏症的研究

对66名汉族飞行人员进行乳糖呼出气氢测定试验,乳糖吸收不良的发生率为83.3％,其中乳糖不耐受者占34.6％;与一般汉族人群无明显差别。对10名确定为中度以上乳糖吸收不良的飞行人员进行250ml鲜牛奶的试验结果,有50％呼出气氢含量在正常范围,并无一例出现胃肠道症状。提示较长期食用牛奶未能使乳糖酶缺乏状态发生改变,但每日食用适量牛奶属合理营养。     

Relationships between Responsiveness of the Bronchi to Acetylcholine and Cyclic AMP Response of Lymphocytes to Beta1- and Beta2-Adrenergic Receptor Stimulation in Patients with Asthma

Decreased response of beta-adrenergic receptor has been considered to he one of the causes of increased responsiveness of the bronchi in asthma. Since beta-adrenergic receptor has two subtypes, beta₁ and beta₂, and the bronchodilating effect of beta stimulants is mediated by beta₂-receptor, responsiveness of the bronchi is expected to correlate to the cyclic AMP response of lymphocytes to a beta₂-stimulant. Responsiveness of the bronchi was expressed as respiratory threshold to acetylcholine (RT-Ach), which was the minimal concentration of acetylcholine solution to cause an initial decrease of FEV₁ of more than 20% of the baseline value. Beta₁ and heta₂-responses were expressed as the increments of cyclic AMP content of 10⁶ lymphocytes incubated with norepinephrine (beta₁-stimulant) and salbutamol (beta₂-stimulant).
RT-Ach showed a significant correlation with the beta₂-cyclic AMP response of lymphocytes, but not with the beta₁ -response among patients with asthma. Sixteen symptomatic patients on continuous beta-stimulants showed lower RT-Ach value and diminished beta₂-receptor activity of lymphocytes compared with 14 patients in remission. These results suggest that selective beta₂-adrenergic blockade may he one of the causes of bronchial hypersensitivity in asthma, though it should be noted that in this study beta-adrenergic responses were examined in lymphocytes and were compared with the responsiveneness of the bronchi. Possible beta-receptor subsensitivity induced by administration of beta-stimulants is discussed.