No association of C-1019G promoter polymorphism of 5-HT1A receptor gene with migraine

It is well known that migraine has a strong genetic component, although the type and number of genes involved remains unclear. There is evidence to suggest that serotonin-related genes may be involved in the pathogenesis of migraine. To investigate whether the 5-HT1A receptor gene contributes to the risk of migraine we performed an association study of C-1019G promoter polymorphism of the gene in 102 migraineurs and 93 controls. Subjects were of Han Chinese origin. No significant differences in allele (P=0.82) or genotype frequencies (P=0.71) were seen in migraineurs compared with the controls. When migraine with aura, without aura, with family history, without family history were analyzed separately, the frequencies did not vary significantly. Our results suggest that C-1019G in 5-HT1A is not a major genetic risk factor for migraine.     

SPM5软件分析癫痫患者脑PET图像的应用研究

Objective To investigate the value of statistical parametric mapping 5 (SPM5) and its parameter settings in analysis of PET imaging for epilepsy patients. Methods Seventeen epilepsy patients and seventeen controls were scanned with PET. The datns were analyzed using PET and SPM5 with qualitative and semiquantitative analysis, statistical analysis of the percentage (numbers of agent distribution decreasing in focus to brain) for different parameters combinations, which were value adjustment to contral-p and voxels-k. Results There was decreasing of agent distribution at temporal lobe in epilepsy patients detecting with PET; the T/NT of focus to cerebellum was 1.07±0.24, the T/NT of normal tissue in opposite side to cerebellum was 1.27±0.18, there was a significant difference (t=1.87, P<0.05). Dealing with SPM5, there was more significant decreasing of agent in regions 19, 21, 39 of temporal lobe, regions 7, 19, 31, 40, 47 of parietal lobe and occipital lobe in epilepsy patients. With different value of k, the percentage was (27±22)%, (29±24)%, (32±23)%, (35±27)%, (39±31)%respectively, there was not significant difference (F=0.59, P>0.05) ; for different value of p, the percentage was (42±30) %, (29±25) %, (26±21) % respectively, with a significant difference (F=3.60, P<0.05); there was linear regression in value adjustment to contral-p and the percentage(b=-18.24, t=2.57, P<0.05). Conclusions Semiquantitative analysis by SPM5, the setting of value adjustment to contral-p would affect the results, the smaller of value adjustment to contral-p, the better of the result. SPM5 would be more objective and accurate to locate the focuses.     

A prospective study of the association of cerebrospinal fluid monoamine metabolite levels with lethality of suicide attempts in patients with bipolar disorder

Objectives:  Bipolar disorder is a severe illness that is associated with suicidal behavior. A biological predictor of highly lethal suicide attempts in patients with bipolar disorder would be valuable. We hypothesized that cerebrospinal fluid (CSF) monoamine metabolite levels are related to lethality of suicide attempts in bipolar patients and examined the relation between CSF 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and maximum lethality of suicide attempts at baseline and during a 2-year follow up.
Methods:  Twenty-seven bipolar depressed patients participated in the study. Demographic and clinical parameters were examined and recorded. Lumbar punctures were performed and CSF 5-HIAA, HVA, and MHPG were assayed by high-performance liquid chromatography with electrochemical detection. Following discharge, patients were evaluated after 3 months, 1 year, and 2 years. Each follow-up interview included an in-depth assessment of suicidal behavior during the intervening time period.
Results:  Six subjects made suicide attempts during the 2-year follow-up. Bipolar patients who attempted suicide during the follow-up period had higher aggression and hostility scale scores compared to bipolar subjects who did not make a suicide attempt during the follow-up period. CSF 5-HIAA, HVA, and MHPG levels were negatively correlated with the maximum lethality of suicide attempts during the 2-year follow-up period.
Conclusions:  Our finding is the first observation that CSF monoamine metabolite levels may be predictors of lethality of suicide attempts in patients with bipolar disorder. Further studies are necessary to answer the question whether CSF monoamine metabolite levels are clinically useful biochemical predictors of highly lethal suicide attempts or completed suicides.     

Mutational specificity of the syn 1,2-dihydrodiol 3,4-epoxide of 5-methylchrysene

The mutational specificity of the syn dihydrodiol epoxide of 5-methylchrysene in the supF gene of the pSP189 vector was examined. Transversion mutations at GC pairs predominated with G → T and G → C changes accounting for 42 and 21% of total base change mutations. The types of mutations found reflect the previously determined chemical preference of this reactive species for reaction with deoxyguanosine residues in DNA.     

薄层扫描法测定复脉定冲剂中远志有效成分的含量

采用薄层扫描法对复脉定冲剂中远志有效成分３，４，５－三甲氧基反式肉桂酸乙酯的含量进行测定。方法简单、快速，结果可靠，可作为该制剂的质控标准。     

About the centrality of mood lowering in mood disorders : Plenary Lecture ECNP Congress, Monte Carlo, October 1991

5-HT disturbances in depression (as exemplified by lowered CSF 5-HIAA) are not syndrome specific but related to components of the depressive syndrome, specifically to increased anxiety and aggression. These 5-HT disturbances are probably core pathogenetic processes not derivative features. I hypothesized that in this subtype of depression, i.e. in “5-HT related depression”, the key psychopathological disturbances are dysregulation of anxiety and aggression, while mood lowering is a “by-product”. Based on this hypothesis it was predicted that agents which ameliorate anxiety and/or aggression via harmonization of 5-HTergic transmission will, in addition, exert overall antidepressant effect in “5-HT related depression”. The study of the relative “weight” of the various psychopathological components of depression is a basic exercise in understanding the nature of that condition and could, as such, greatly facilitate the goal-directed search for new and innovative antidepressants.     

Effect of the 5-HT1 agonist sumatriptan on oesophageal motor pattern in patients with ineffective oesophageal motility

The 5-HT1 agonist sumatriptan (SUM) elicits an increase in amplitude of oesophageal motor waves and of lower oesophageal sphincter (LOS) tone in healthy subjects. The aim of the study was to evaluate whether such an effect occurs also in patients with ineffective oesophageal motility (IOM). 16 patients (nine males and seven females, age range 34-55 years) with chest pain and mild to moderate dysphagia were studied; all had undergone previous cardiologic, radiologic and upper gastrointestinal endoscopic exams that were normal. An oesophageal manometry was performed using an electronic probe to record swallows, oesophageal, LOS and gastric motility. The patients whose motor pattern were compatible with IOM (>30% of motor waves with amplitude <30 mmHg and/or non-transmitted) received SUM or placebo 6 mg s.c., injected in the morning and in the afternoon in a random order. The data analysis was limited to 1 h before and 1 h after the drug injections. Ten out of the 16 patients showed an IOM motor pattern. The administration of SUM caused a significant increase in the number of swallows (SUM 99.5 +/- 15.4 vs 78.6 +/- 16.1 basal, P = 0.03) and of primary oesophageal motor waves (SUM 89.6 +/- 13.4 vs 67.2 +/- 12.9 basal, P = 0.04) with no significant changes in the percentage of swallows associated with propagation. Placebo was not associated with increase in the number of swallows (80.3 +/- 14.6, P = 0.9) or of primary oesophageal motor waves (70.1 +/- 12.3, P = 0.7). The amplitude and the percentage of propagated oesophageal motor waves as well as the mean basal LOS tone were unaltered by SUM. There was no change in the symptoms reported after SUM. Although effective in healthy subjects, SUM 6 mg s.c. improves only the numbers but not the amplitude or propagation of oesophageal motility of patients with IOM. The 5-HT1 pathway and its acute stimulation seem to play only a minor role in the pathogenesis of such a disease.     

抗棘球蚴药物研究:3-取代苯基-5-取代-1,2,4-噁二唑的合成

合成了3-取代苯基-5-取代-1,2,4-(口恶)二唑类化合物50个,经感染棘球蚴的小鼠初筛,部分化合物对棘球蚴有不同程度的作用,化合物13、28和30对棘球蚴的囊重抑制率分别为70、75.6和71.6%,其中化合物13对棘球蚴的生发层有损害作用。     

Heparin–coated circuit during cardiopulmonary bypass

A prospective randomized study was performed to investigate the effect of surface coating with covalently endpoint–attached heparin (Carmeda Bio Active Surface) and reduced general heparinization on haematological indices and complement C5 activation. Care was taken to optimize the rheological design of the system using centrifugal pump and a closed system without venting or machine suction. Twenty patients scheduled for aortocoronary bypass grafting (EF > 0.5) participated in the study. Ten patients were randomized to be treated with heparin–coated equipment (CBAS) and reduced i.v. heparin (1.5 mg kg^-1) while 10 patients treated with identical but noncoated equipment and full heparinization (3 mg–kg^-1) served in a Control group. A vacuum suction was used to collect the blood from the operating field and it was autotransfused at weaning from extracorporeal circulation (ECC). Blood samples were obtained from the venous (precircuit) and arterial (postcircuit) side. We used a new and very specific method for detection of C5a based on monoclonal antibodies. The concentration of C5a was low in both groups during the operation but a significant increase was seen on days 1 and 2. In the Control group there was an increase from 10.2 ngml^-1±1.2 to 27.5 ng ml^-1 ± 4.8 on day 2 and in the CBAS group from 10.7 ng ml^-1 ± 1.2 to 35.6 ng ml^-1 ± 11.6 on day 2 (NS between groups). The granulocytes and total leukocyte count increased at the end of ECC and was maintained at the elevated level throughout the study period. The amount of free haemoglobin was high in the autotransfused blood in both groups. The present results confirm the feasibility of reducing general heparin when using heparin–coated systems but the study does not support the superiority of such coating with regard to biocompatibility in short procedures with a Theologically optimized circuit. The potential benefit from reduced heparin and protamine has not been fully evaluated.     

Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants

This study demonstrated that distinct patterns of active behaviors are produced by antidepressants that selectively inhibit norepinephrine (NE) or serotonin (5-HT) uptake in the rat forced swimming test (FST). A behavior sampling technique was developed to score the active behaviors swimming, climbing and diving, as well as immobility. The rat's behavior was recorded at the end of each 5-s period during the test session. The sampling technique was both reliable, as demonstrated by test-retest reliability and inter-rater reliability, and valid, as shown by comparison to the timing of behavior durations. Five different antidepressant drugs which block monoamine uptake and two 5-HT_1A receptor agonists were shown to decrease immobility in the FST; however, they produced distinct patterns of active behaviors. The selective NE uptake inhibitors desipramine and maprotiline selectively increased climbing, whereas the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline and paroxetine selectively increased swimming. The 5-HT_1A receptor agonists 8-OH-DPAT and gepirone also selectively increased swimming. These results show that:1) SSRIs are not false negatives in the FST; 2) at least two behaviorally distinct processes occur in the FST; and 3) enhancement of NE neurotransmission may mediate climbing in the FST, whereas enhancement of 5-HT neurotransmission may mediate swimming.