Preventive effect of magnesium supplement on noise-induced hearing loss in the guinea pig

The effect of magnesium (Mg) on noise-induced hearing loss was investigated in two groups of adult pigmented guinea pigs maintained either on optimal or suboptimal (physiologically high or low) Mg produced by different diets. The total Mg concentrations of the perilymph (PL), cerebrospinal fluid, blood plasma and red blood cells were measured by atomic absorption spectrometry and were found to differ significantly between the two groups (P < 0.01). One ear of each animal was exposed to either a single shooting impulse at a peak pressure level of 187 dB or two impulse noise series at a rate of 1/s and peak pressure levels of 150 dB (1,000 impulses) and 167 dB (2,280 impulses), respectively. Temporary (TTS) and permanent (PTS) hearing threshold shifts in anesthetized animals were measured 2 h and 1 week after the noise exposure, using auditory brain stem response (ABR) audiometry at a frequency range from 3.75 to 30 kHz. Exposure to the single noise impulse resulted in a mean TTS that was significantly lower in the high Mg group than that in the low Mg group (P < 0.05), although no substantial PTS was observed in either group. In the animals exposed to 150 dB noise, the TTS showed a tendency towards an Mg-related reduction at the higher frequencies. A small difference in PTS was found between the low Mg and high Mg groups, but was not significant. Exposure to the 167-dB noise series caused a considerable TTS, which was significantly lower in the high Mg group at 7.5 and 15 kHz than in the low Mg group (P < 0.05). The mean PTS showed a significant difference between the two Mg groups over the whole frequency range (P < 0.05) and was found to correlate negatively with the total Mg concentrations of both PL and plasma (P < 0.05). Moreover, the high Mg group showed a faster recovery from the hearing threshold shift than the low Mg group. The present findings show that preventive oral Mg supplements can significantly reduce the rate of acoustic trauma caused by high-level impulse noise exposure in the guinea pig. Received: 23 March 1999 / Accepted: 15 April 1999     

后半规管阻塞前后豚鼠前庭及耳蜗功能的动态变化

目的 探讨机械性后半规管阻塞前后豚鼠前庭和耳蜗功能的动态变化。方法 采用２０只豚鼠建立单侧后半规管阻塞的动物模型,观察手术前后眼震电图,听性脑干反应,耳声发射等变化。结果 术后第１天,第３天豚鼠正弦摆动刺激术侧眼震反应,明显减术,术后第５天起双侧眼震恢复正常。术后早期ＡＢＲ阈值一度升高,第５天达高峰,ＡＢＲ阈值平均升高４．５ｄＢ。ＤＰＯＡＥ反应幅度无明显改变。结论 后半规管阻塞能选择性地消除后半规     

袖套法豚鼠至大鼠异种全胰十二指肠移植模型的建立

目的为研究超急性排斥反应及对策,建立异种胰腺移植模型。方法以豚鼠和大鼠为供受者,用袖套法吻合静脉建立异种全胰十二指肠移植模型。结果共行 ４２次手术,成功 ３８例,均有内分泌功能,移植有效率为 １００％。结论本模型具有操作简单,冷缺血及腹主动脉阻断时间短,不易形成血栓及吻合口漏等优点,为一较实用的研究异种胰腺移植模型。     

侧柏叶乙酸乙酯提取物对豚鼠离体气管平滑肌的作用

用离体豚鼠气管条,探讨侧柏叶乙酸乙酯提取物对气管平滑肌作用。结果表明,侧柏叶乙酸乙酯提取物能抑制乙酰胆碱,氯化钾所致气管平滑肌收缩,而且能使乙酰胆碱收缩气管平没肌的量效曲线右移,并抑制最大效应,其作用为剂量依赖性心肌肥厚提示侧柏叶乙酸乙酯提取物松驰气管平滑肌作用机制可能与影响Ｃａ＾２＋的跨膜转运有关。     

Preservation of the non-rectangular cuticular plate/cell axis angle of outer hair cells

Motile properties of outer hair cells (OHCs) may contribute to sharp tuning and amplification in the mammalian cochlea. Shape changes of isolated OHCs in response to various physical and chemical influences have been investigated intensively. However, determinations of shape may have been influenced by unanticipated effects of preparation and preservation of the OHCs investigated. Thus, in a first step, lengths of freshly isolated OHCs from the guinea pig cochlea were determined using a video-enhancing magnification system. The cuticular plate/cell axis angle (CP/CA angle) was then measured in native cells and under the influence of potassium chloride and potassium gluconate incubation. To show the influence of glutaraldehyde (GA) fixation on the isolated OHCs, fixative dependent changes on cell length and CP/CA angle were recorded in native and preincubated OHCs. In these experiments, the cell length of vital isolated OHCs was between 41.5 m, in the basal turn, and 103.7 m, in the apical turn. The average CP/CA angle was 106° ± 4.2° (n = 324 cells, turns 1–4) with no statistically significant differences for the four turns. Under the influence of potassium chloride, cell length was reduced by 8.1%. Potassium gluconate incubation led to a shortening of cell length, followed by a 5.3% increase after 5 min. The CP/CA angle under potassium chloride was decreased (97.0°) and was then increased under the influence of potassium gluconate (110.7°) as a result of cuticular plate tilting. Cell shrinkage after fixation depended on the fixative's osmolarity and on the GA concentration. Increased GA levels amplified cell shrinkage from 34% for hypo-osmolar solutions to 15% in iso-osmolar and 29% in hyperosmolar solutions. The CP/CA angle of native and incubated OHCs was not different from those fixed with GA. The present data provide a rational basis for isolated OHC shape parameters. Moreover, functionally induced changes can be better interpreted when OHCs are influenced by fixatives, as shown in the GA experiments.     

Effect of the phosphodiesterase inhibitor 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (ZK 62711) on gastric secretion and gastric mucosal cyclic AMP

Summary The effect of the phosphodiesterase inhibitor 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (ZK 62711) on gastric secretion and the cyclic AMP system of the gastric mucosa was studied in rats and guinea pigs. In rats, 0.03–0.3 moles/kg ZK 62711 i.v. stimulated acid and pepsin secretion in a dose-dependent manner and 0.03 moles/kg i.v. enhanced the effect of histamine. In guinea pigs no reproducible stimulation was found after intravenous injections of ZK 62711. The stimulation of gastric secretion in the rat by 0.3 moles/kg ZK 62711 i.v. was not affected by vagotomy but was totally inhibited by 10 moles/kg cimetidine i.v. The structurally related phosphodiesterase inhibitor, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidine (Ro 20-1724), at the dose of 3.3 moles/kg i.v. stimulated gastric secretion in anaesthetised rats to a similar extent as 0.3 moles/kg ZK 62711 i.v. The content of cyclic AMP in the rat gastric mucosa in vivo was slightly increased by 10 moles/kg ZK 62711 i.v, whereas lower doses did not change it. Accumulation of cyclic AMP in the rat gastric mucosa by 50 moles/kg histamine i.v. was enhanced by simultaneous injections of 3.3 moles/kg ZK 62711 i.v. In rat gastric tissue slices in vitro 1–50 M ZK 62711 increased the level of cyclic AMP but 100 M histamine had no effect in the absence or presence of ZK 62711. In gastric mucosal slices of the guinea pig 10 and 50 M ZK 62711 increased the cyclic AMP content which effect was inhibited by 100 M cimetidine and enhanced the stimulatory effect of 100 M histamine on cyclic AMP. The activity of soluble cyclic AMP phosphodiesterase was inhibited by ZK 62711 in the rat (IC₅₀=18 M) and guinea pig gastric mucosa (IC₅₀=1.5 M). Adenylate cyclase was not affected in the homogenate of the guinea pig gastric mucosa. The results indicate that the phosphodiesterase inhibitor ZK 62711 which increases cyclic AMP levels in the gastric mucosa in vivo and in vitro, is a potent stimulator of gastric acid secretion.     

Hybrid information provided by the 14C-aminopyrine breath test studies with 14C-monomethylaminoantipyrine in the guinea pig

Summary N-Demethylation of ¹⁴C-aminopyrine (¹⁴C-AP), labelled at the methyl groups of the tertiary amino group, yields H¹⁴CHO and ¹⁴C-monomethylaminoantipyrine (¹⁴C-MMAAP) which also undergoes N-demethylation, however, at a slower rate as measured in hepatic microsomes. As after intraperitoneal application to male guinea pigs of ¹⁴C-AP (75 mg/kg; 50 Ci/kg), exhalation rate of ¹⁴CO₂ declines in a biphasic manner, the hypothesis was tested whether the terminal part might reflect N-demethylation of MMAAP. The application of ¹⁴C-MMAAP (70 mg/kg; 10 Ci/kg), resulted in monophasic curves of ¹⁴CO₂ exhalation rate. Their half lives were, however, longer than terminal half lives obtained after ¹⁴C-AP. Obviously, this terminal phase does not represent ¹⁴CO₂ formation from the metabolite MMAAP only, but ¹⁴C-AP might still contribute to ¹⁴CO₂ production. Confirmation was obtained by HPLC determination of AP and MMAAP in serum after injection of AP. Shortly after injection, high concentrations of AP and low ones of MMAAP were found in blood from the portal vein and systemic circulation. Thus, initial parts of ¹⁴CO₂-exhalation rate curves reflect predominantly AP metabolism whereas later phases provide hybrid information.     

Allergen tachyphylaxis of guinea pigs in vivo: A prostaglandin E mediated phenomenon?

Ovalbumin (OA) sensitized guinea pigs were repeatedly challenged with 1% OA in saline nebulized ultrasonically at the 0, 10, 20, 60 and 70th min. The intensity of bronchial obstruction was measured by body plethysmography. The first three challenges (0, 10, 20 min) caused strong asthmatic reactions in all animals, the last two (60, 70 min) only mild ones in 10 out of 15 animals. The development of this tachyphylaxis was markedly reduced by pretreatment of the animals with cyclooxygenase inhibitors (indomethacin 10 mg/kg intraperitoneally resp. acetylsalicylic acid 10 mg/kg orally 2h before test). The effect of both inhibitors (i.e. inhibition of tachyphylaxis) was abolished by supplementing prostaglandin E₂ as aerosol simultaneously to the allergen (100–200 ng per inhalation). The results suggest that allergen tachyphylaxis we have observed in vivo might be due to synthesis of cyclooxygenase products, e.g. prostaglandin E.Supported by Deutsche Forschungsgemeinschaft (grant Do 240) in part presented at the 17th workshop on pediatric research [Göttingen 1981, Eur. J. Pediatr. 135: 336 (1981)]     

pD2-, pA2- and pD2'-values of a series of compounds in a histaminic and a cholinergic system.

(1) Affinity and intrinsic activity values of 75 compounds for a histaminergic and a cholinergic system are presented. The quantitative correlations between the affinity values of 35 compounds and some physicochemical constants (Van der Waals volume, lipophilicity, number of hydrogen atoms on the protonated amine) are discussed. (2) Absence of systematic differences between pD2 and pA2 of partial agonists supports the assumption that these values are equivalent expressions of the same affinity. (3) The "mimetic moiety" in a number of the antihistaminic test compounds hardly contributes to their affinity. The affinity mainly depends on an interaction tendency with additional receptor areas. (4) The correlation between pA2 and pD2' of the whole series of compounds in the histaminergic system is artificial. The method only allows determination of both values if their ratio lies between certain limits. (5) The correlation between pA2 and pD2' for 16 closely related compounds in the guinea pig ileum and for nearly all compounds in the rat intestine has to be explained by an influence of the structural differences on drug transference and/or the less specific binding forces. (6) The metactoid receptors in the two systems are different structures. (7) Possible molecular modifications to maximize the separation of antihistaminic form cholinergic affinity are suggested.