The attenuation by Δ 9-Tetrahydrocannabinol and morphine of the quasi-morphine withdrawal syndrome in rats

The effect of ⁹-tetrahydrocannabinol (THC), morphine, haloperidol and chlordiazepoxide on the exhibition of the signs of the quasi-morphine withdrawal syndrome was studied in rats. In preliminary studies approximately equi-sedative doses of these drugs were chosen. Morphine and THC produced a very similar degree of suppression of the signs of the quasi-morphine withdrawal, but unlike morphine, the effects of THC were not reversed by the narcotic antagonist, naloxone. The dopamine receptor antagonist, haloperidol, produced a moderate suppression of the withdrawal syndrome and chlordiazepoxide was without significant effect. It is concluded that THC is of very similar potency to morphine in suppressing the quasi-morphine withdrawal syndrome, but its activity in this regard does not appear to be dependent upon the availability of opiate or dopamine receptors, nor is it due to sedation alone.To whom offprint requests should be sent     

Is sleep-disordered breathing an independent risk factor for hypertension in the general population (13,057 subjects)?

Objective: Sleep-disordered breathing has been hypothesized to have a close relationship with hypertension but previous studies have reported mixed results. This is an important health issue that requires further clarification because of the potential impact on the prevention and control of hypertension.Methods: The relationship between hypertension and three forms of sleep-disordered breathing (chronic snoring, breathing pauses and obstructive sleep apnea syndrome (OSAS)) was assessed using representative samples of the non-institutionalized population of the UK, Germany and Italy (159 million inhabitants). The samples were comprised of 13,057 individuals aged 15–100 years who were interviewed about their sleeping habits and their sleep symptoms over the telephone using the Sleep-EVAL system.Results: OSAS was found in 1.9% (95% CI: 1.2% to 2.3%) of the UK sample, 1.8% (95% CI: 1.4% to 2.2%) of the German sample and 1.1% (95% CI: 0.8% to 1.4%) of the Italian sample. OSAS was an independent risk factor (odds ratio (OR): 9.7) for hypertension after controlling for possible confounding effects of age, gender, obesity, smoking, alcohol consumption, life stress, and, heart and renal disease.Conclusions: Results from three of the most populated countries in Western Europe indicate that OSAS is an independent risk factor for hypertension. Snoring and breathing pauses during sleep appeared to be non-significant predictive factors.     

Stage of specification of the spinal cord and tectal projections from cortical grafts

In order to determine the embryonic age at which the hodological phenotype developed by neocortical cells is specified, we have examined the spinal or tectal projections developed by embryonic (E) grafts of presumptive frontal or occipital neocortex placed into the frontal or occipital neocortex of newborn host rats. Grafts of E13, E14 and E16 cells of the frontal cortex transplanted into the occipital cortex of newborns are capable of developing and maintaining in adulthood a spinal cord axon. Grafts of E12 cells do not project to the spinal cord but send fibres to the superficial layers of the tectum. In addition, following transplantation into the frontal cortex, early embryonic (E12) cells from the presumptive occipital cortex are capable of differentiating into neurons with spinal cord projection but are practically incapable of developing a tectal projection. When grafted at E14 into the frontal cortex, occipital cells lose the capacity to project to the spinal cord but become able to send fibres to the tectum. Taken together, these findings indicate that young (E12) embryonic frontal and occipital cortical cells are competent to subsequently differentiate into neurons projecting to the spinal cord or tectum according to instructive signals available in the cortical territory where they complete their development. By E13/E14, some cortical cells are specified and their capacity to contact targets that are not appropriate to their embryonic origin is much reduced. These findings are consistent with the notion that cortical specification involves progressive restriction in cell multipotentiality and fate specification toward region-specific phenotypes.     

Reversible protein kinase C activation in PC12 cells: effect of NGF treatment

Although protein kinase C (PKC) is a key enzyme in the signal transduction process, there is little information on the mechanism leading to PKC activation in living cells. Using a new fluorescence imaging method, we studied this mechanism and correlated PKC conformational changes with intracellular Ca2+ concentration. PC12 cells were simultaneously loaded with Fura-2-AM and Fim-1, two fluorescent probes, which recognize Ca2+ and PKC, respectively. KCl and carbachol (an agonist to muscarinic receptors) applications induced dose-dependent increases of fluorescence for both probes. Both Ca2+ and PKC responses were observed within seconds following KCl or carbachol application, and were reversible upon stimulus withdrawal. PKC activation kinetics was slightly more rapid than the Ca2+ response after KCl application. After nerve growth factor (NGF) treatment of the cells, the amplitude of the KCl-induced PKC responses was larger indicating an increase in the activated PKC-pool in these cells. This difference between control and NGF-treated cells was not observed following carbachol application, suggesting the involvement of different PKC pools. While the Ca2+ response uniformly occurred in the cytosol, the PKC response displayed a patch pattern with higher intensities in the peripheral zone near the plasma membrane. This heterogeneous distribution of PKC activation sites was similar to the immunocytological localization of Ca2+-dependent and independent PKC isoforms, which suggested that at least several PKC isoforms interacted with intracellular elements. Upon repeated stimulation, the PKC response rapidly desensitized.     

Impaired cholinergic function in cell lines derived from the cerebral cortex of normal and trisomy 16 mice

Murine trisomy 16 is an animal model of human Down's syndrome. We have successfully established permanently growing cell lines from the cerebral cortex of normal and trisomy 16 foetal mice using an original procedure. These lines, named CNh (derived from a normal animal) and CTb (derived from a trisomic foetus), express neuronal markers. Considering that Down's syndrome exhibits cholinergic deficits, we examined cholinergic function in these lines, using incorporation of [3H]-choline and fractional release studies. After 1, 3 and 5 min of [3H]-choline incubation, CTb cell uptake was lower by approximately 50% compared to controls. Hemicholinium-3 significantly reduced the incorporation of [3H]-choline in both CNh and CTb cells at high concentration (10 microM), suggesting high-affinity choline transport. However, CTb cells exhibited greater sensitivity to the blocker. For fractional release experiments, the cells were stimulated by K+ depolarization, glutamate or nicotine. When depolarized, CTb cells showed a 68% reduction in fractional release of [3H]-acetylcholine compared to CNh cell line, and a 45% reduction when stimulated by nicotine. Interestingly, glutamate induced similar levels of release in both cell types. The results indicate the existence of cholinergic dysfunction in CTb cells when compared to CNh, similar to that reported for primary cultures of trisomy 16 brain tissue (Fiedler et al. 1994, Brain Res., 658, 27-32). Thus, the CTb cell line may serve as a model for the study of Down's syndrome pathophysiology.     

Esophageal pressure and apnea hypopnea index in sleep-disordered breathing

Severity of negative esophageal pressure (Pes) and apnea hypopnea index (AHI) were investigated in six cases of upper airway resistance syndrome (UARS) and 11 cases of obstructive sleep apnea syndrome (OSAS). The severity of negative Pes was represented by the highest peak (Pes Max) and the number of increased episodes (more than 13.5 cmH2O) per h (NPesI13.5). There was no significant correlation between Pes indices and AHI. Pes Max and NPesI13.5 were not different among severe OSAS (AHI > 30), mild OSAS (AHI < 30) and UARS. Apnea hypopnea index failed to represent the severity of negative Pes, which is an important aspect of the pathophysiology of sleep-disordered breathing.     

Effect of 3 mg melatonin on jet lag syndrome in an 8-h eastward flight

In order to assess the effect of melatonin on jet lag a field study was undertaken. The process of re-entrainment of circadian melatonin rhythm was investigated in six subjects. Except during 24-h blood sampling, the subjects were exposed to natural zeitgeber (time giver) outdoors and given 3 mg melatonin at 23:00 h. The subjects were exposed to bright sunlight from 3000 to 12000 lx. All of them showed orthodromic re-entrainment with taking melatonin, while two out of the six did not show orthodromic re-entrainment without taking melatonin. Melatonin accelerated the rate of the re-entrainment of the circadian melatonin rhythm. Melatonin was useful to jet travel from Tokyo to Los Angeles.     

氟伐他汀治疗肾病综合征高脂血症的量效观察

目的　观察氟伐他汀对肾病综合征高脂血症剂量与疗效的关系。方法　在常规治疗的基础上 ,6 4例肾病综合征高脂血症患者分为 2组 ,A组 33例口服氟伐他汀 80mg/d ,B组 31例口服氟伐他汀 2 0mg/d ,观察疗效和安全性。结果　A组服药 2周后 ,血清TC ,TG ,LDL -C水平与治疗前比较分别降低 2 4 .6 5 % ,2 5 .0 8% ,32 .0 3% (P <0 .0 0 1) ;B组分别降低4 .83% ,0 .33% ,5 .87% (P >0 .0 5 )。以上结果的组间比较均有统计学差别。A组服用 2周时降低TC ,TG ,LDL -C的显效率及降低TC总有效率均明显高于B组。两组治疗期间均未发现明显的不良反应。结论　氟伐他汀治疗肾病综合征高脂血症时 ,治疗效果与剂量存在明显的正相关 ,对肾病综合征高脂血症患者应采用大剂量氟伐他汀方法 ,对及时纠正高脂血症、改善病情有利     

辨证分期治疗慢性盆腔炎合并免疫性不孕症18例疗效观察

目的：探讨辨证分期治疗慢性盆腔炎合并免疫性不孕症的临床疗效。方法：选择慢性盆腔炎合并免疫性不孕症(血清抗精子抗体阳性)患者18例，采用辨证分期治疗。月经干净后，治以活血化瘀、理气祛湿为主；在(或相当于)排卵期或排卵后，治以补肾养血，活血化瘀为主；在经前期，治以理气活血调经为主；在月经干净后至经前期，加用小剂量阿司匹林。结果：盆腔炎临床症状及体征痊愈7例，显效6例，有效5例；全部患者获得妊娠，宫内妊娠者17例(观察至妊娠3月，均正常)，输卵管妊娠1例；结论：中医辨病辨证结合的周期疗法加小剂量阿司匹林治疗慢性盆腔灸合并免疫性不孕症有一定的疗效。     

视疲劳综合征的研究概况

视疲劳综合征是以眼部各种不适症状为突出表现的一组症侯群。作者综述了目前对视疲劳的定义、分类、诊断和治疗方面的研究进展。