The Effect of Immunosuppression by Total-Body Irradiation on the Pharmacodynamics of Centrally Active Drugs in Rats

The aim of this investigation was to assess whether immunosuppression induced by total-body irradiation (TBI) affects the pharmacodynamics of centrally acting drugs. Female Sabra rats were exposed to a single dose of gamma irradiation (5.3 Gy). Four days later, when both the cellular and the humoral immune responses were impaired, they received an i.v. infusion of either phenobarbital (0.8 mg/min), ethanol (16.3 mg/min), pentylenetetrazol (PTZ; 0.618 mg/min), or theophylline (as aminophylline; 2 mg/min). The infusion was stopped at the onset of the pharmacologic end point—loss of righting reflex for the depressant agents or maximal seizures for the stimulant drugs—and the concentrations of the neuroactive drugs at that point were determined. In the ethanol experiment, blood samples were also taken upon awakening. The radiation-induced immunosuppression significantly decreased the CNS sensitivity to the depressant action of both phenobarbital and ethanol as indicated by the higher CSF phenobarbital concentrations required to induce sleep in the irradiated rats versus controls (156±4 vs 133 ±5 mg/L, respectively; P < 0.05), and the higher serum ethanol concentrations at the onset and offset of sleep in the immunosuppressed group versus control values (4.6±0.2 and 1.68±0.01 vs 3.79±0.17 and 1.32±0.9 mg/mL, respectively; P < 0.04). Exposure to TBI did not alter the pharmacodynamics of the two convulsant drugs (theophylline andPTZ).     

Expired-breath ethanol measurement in chronic obstructive pulmonary disease: implications for transurethral surgery

If ethanol is added to the irrigant used during transurethral prostatic resection, the absorption of fluid can immediately be detected by measuring the ethanol concentration in the expired breath. To evaluate this method further, we studied the influence of chronic obstructive pulmonary disease (COPD) on the agreement between expired-breath and blood-ethanol concentrations. In 14 men with a mean age of 62 years (range 55-68), the concentrations of ethanol in whole blood and end-expired breath were measured at 12 exactly timed intervals before, during, and after an intravenous infusion of 0.6 g.kg-1 ethanol for 60 min. The pulmonary function was normal in seven of the subjects (control group) whereas the other seven suffered from severe COPD (study group). The results show that the accuracy and precision of breath-alcohol analysis to predict the blood-ethanol level were poorer during the infusion of ethanol than afterwards. However, at all times of sampling the estimation of blood-ethanol concentration indirectly by analysis of breath was not significantly different for COPD patients and the control group. We conclude that ethanol monitoring of irrigant absorption can be used successfully in patients with COPD.     

Ethanol Reduces Myoglobin Release during Isokinetic Muscle Exercise

ABSTRACT. Changes in serum myoglobin concentrations were studied in 12 healthy males performing a standardized isokinetic 2-min exercise test. The test was performed on three separate occasions: in the habitual state, during moderate ethanol intoxication and one day after ethanol intake. Although the performed muscle work, maximal heart rate, and blood lactate levels did not differ between the three test occasions, the serum myoglobin increments after exercise were significantly reduced (p < 0.05) in the ethanol-intoxicated state and also 10–15 hours after ethanol intake. The reduction of the exercise-induced myoglobin increment was not explained by increased elimination of the protein. The mechanism, therefore, is likely to be a reduction of myoglobin release from skeletal muscle due to an ethanol-induced alteration of the muscle cell membrane, possibly by means of adenylate cyclase activation.     

d-儿茶精对乙醇中毒小鼠肝线粒体急性损伤的影响

本文探讨d-儿茶精对乙醇诱导鼠肝线粒体急性损伤的修复作用。结果证实:该化合物降低模型动物肝线粒体膜脂质膜流动性,增加肝线粒体GSH含量,减少Ca~(2+)的摄取和脂质过氧化物生成。通过对抗乙醇的毒素作用缓解了肝线粒体膜结构的急性损伤。     

毛细管气相色谱法测定萘哌地尔中的残留溶剂

目的:建立气相色谱法分离测定萘哌地尔中的残留溶剂:乙醇、乙酸乙酯、氯仿、正丁醇、环氧氯丙烷。方法:以RX-5弹性石英毛细管柱为色谱柱(25m×0.32 mm),载气为氮气,采用氢离子火焰检测器,进样口温度为220℃,检测器为280℃,柱温采用程序升温,(60℃,保持4min,以10℃·min~(-1)升至100℃,并保持1min,再以25℃·min~(-1)升至220℃保持6 min),以二甲基亚砜为溶剂,进样量1μL。结果:乙醇、乙酸乙酯、氯仿、正丁醇、环氧氯丙烷的的进样量分别在25～400ng,其峰面积与浓度呈良好的线性关系,加样回收率(n=5)分别为99.47％(RSD<0.76％),99.03％(RSD<1.4%),97.91%(RSD<1.4%),97.90%(RSD<1.4%),98.02(RSD<1.4%),精密度良好。结论:本文气相色谱条件可用于同时测定萘哌地尔中乙醇、乙酸乙酯、氯仿、正丁醇、环氧氯丙烷的含量,方法简单准确。     

In vivo monitoring of hepatic oxygenation changes in chronically ethanol-treated rats by functional magnetic resonance imaging.

In this study, functional magnetic resonance imaging (fMRI) was used to evaluate in vivo hepatic oxygenation changes in chronically ethanol (CE)-treated and pair-fed (PF) control rats. Male Wistar rats were pair-fed an all-liquid diet containing 36% of total calories as either ethanol or dextrin-maltose for 8 weeks. The rats were initially examined under normoxic conditions, and then subjected to 100% oxygen (hyperoxia), 10% oxygen (hypoxia), 5% carbon dioxide (hypercapnia), or an acute dose of ethanol (1.4 g/kg bw intraperitoneally). A T(2)-weighted spin-echo sequence, which may be more selective for sinusoidal (capillary bed) changes, was performed before, during, and after the four challenges. During hyperoxia, both the CE and PF rats showed a statistically significant increase in signal intensity (22% +/- 5% and 48% +/- 6%, respectively, P < 0.05) relative to normoxia, while hypoxic challenge decreased the signal intensity (9% +/- 4%, p>0.05 and 15% +/- 3%, P < 0.05, respectively). The hypercapnic challenge, which causes vasodilation, resulted in a small increase in signal intensity in CE-fed rats (5% +/- 3%, P > 0.05) and a significant increase in the PF rats (15% +/- 4%, P < 0.05), again consistent with expected changes in deoxyhemoglobin. With all three physiological challenges, the degree of change was less in CE rats compared to PF controls. An acute dose of ethanol that causes vasodilation also increased signal intensity, with no significant difference between the two groups. The signal intensity changes seen with fMRI were highly correlated with pulse oximeter readings (r(2) = 0.95; P < 0.05). In conclusion, fMRI was shown to be a good noninvasive indicator of tissue deoxyhemoglobin changes in the liver. In addition, fMRI was able to detect subtle, early effects of CE administration (manifested as an impaired ability of the liver to respond adequately to oxygenation challenges), consistent with microvascular dysfunction.     

TACE、PEI、PVC三介入联合治疗中晚期肝癌

目的 分析TACE、PEI、PVC三介入联合治疗中晚期原发性肝癌的临床疗效. 方法 将晚期原发性肝癌60例,分为两组进行治疗:经导管肝动脉栓塞化疗(TACE)组30例(对照组);TACE联合CT引导下无水酒精注射及/或门静脉化疗,即三介入联合治疗组30例(联合治疗组).观察两组间的生存率及门脉癌栓的消失率. 结果 对照组6、12、18、24个月生存率分别为56.7%(17/30)、40%(12/30)、20%(6/30)、6.7%(2/30),门脉癌栓消失率43.75%(7/16).而治疗组6、12、18、24个月生存率分别为76.7%(23/30)、56.7%(17/30)、36.7%(11/30)、16.7%(5/30),门脉癌栓消失率为64.7%(11/17).两组间生存率及门脉癌栓消失率均有统计学意义(P＜0.05). 结论 三介入联合治疗优于单纯栓塞化疗.     

The effect of cannabinoid CB(1) receptor antagonist rimonabant (SR-141716) on ethanol drinking in high-preferring rats.

The present study investigated the effect of the cannabinoid CB(1) receptor antagonist, rimonabant (SR-141716) on ethanol intake in selectively bred alcohol-preferring Warsaw High-Preferring rats. Ethanol (10% vol/vol) and food were available in daily 4-h limited access period while water was available ad libitum. The administration (i.p.) of single 2.5 and 5.0-mg/kg doses of rimonabant preferentially reduced ethanol intake, whereas a 10mg/kg dose of rimonabant similarly reduced both ethanol and food intake. Our result extends the suppressive effect of cannabinoid CB(1) receptor antagonist to the ethanol drinking behavior in Warsaw High-Preferring line of rats. The result also supports a growing body of literature indicating that the cannabinoid CB(1) receptor is involved in motivational and appetitive properties of ethanol.     

Ethanol modulates the ionic permeability of sodium channels in rat sensory neurons

The effects of ethanol on tetrodotoxin-sensitive (TTX_s) and tetrodotoxin-resistant (TTX_r) sodium channels in rat spinal ganglia were studied using a patch-clamp method. Application of ethanol (10 and 100 mM) to both sides of membranes resulted in decreases in the reversion potentials of both types of sodium channels. In the case of TTX_r channels, ethanol decreased their selectivity in relation to Na ions and altered the sequence of ion selectivity of these channels for different cations from row X to row XI of the Eisenman selectivity classification. It is suggested that this change in ion selectivity is associated with ethanol-induced disruption of hydrogen bonds which stabilize the spatial structure of ion channel macromolecules, whith may lead to changes in the steric parameters of the pores formed by these channels. Translated from Rossiskii Fiziologisheskii Zhurnal imeni I. M. Sechenova, Vol. 85, No. 1, pp. 110–118, January, 1999.