脑脊液神经元特异性烯醇化酶与急性白血病

目的探讨神经元特异性烯醇化酶(NSE)对中枢神经系统白血病早期诊断的临床意义和和三联药物鞘注(甲氨喋呤、阿糖胞苷、地塞米松)对中枢神经系统的损伤作用.方法2004～2006年在我院收治的急性非淋巴细胞白血病10例、急性淋巴细胞白血病23例和中枢神经系统白血病5例,用电化学发光法测定脑脊液中神经元特异性烯醇化酶浓度,同时用放射免疫法测定脑脊液中β2微球蛋白浓度.结果中枢神经系统白血病患者脑脊液神经元特异性烯醇化酶浓度(11.56±4.52ng/m1)与急性白血病组(9.59±3.42ng/ml)比较无统计学差异,三联药物鞘注后10d(11.15±3.49ng/ml)、20d(12.32±3.55 ng/ml)、56d(10.76±2.76 ng/ml)与鞘注前(9.96±3.37 ng/ml)比较无统计学差异.中枢神经系统白血病患者脑脊液β2微球蛋白(5.42±1.1mg/l)明显高于急性白血病组(1.67±0.21mg/l).结论脑脊液神经元特异性烯醇化酶作为中枢神经系统白血病诊断指标有待于探讨:三联药物鞘注近期内对中枢神经系统无损伤作用,是安全有效的;脑脊液中β2微球蛋白对中枢神经系统白血病的诊断有重要意义.     

The ontogenetic development of concentration differences for protein and ions between plasma and cerebrospinal fluid in rabbits and rats

1. The purpose of this study was to study in rats and rabbits the ontogenetic development of the blood-brain barrier to macromolecules and the ontogenetic development of concentration differences between plasma and cerebrospinal fluid for ions which are known to be transported actively across the choroid plexus and the blood-brain barrier.2. By comparing the development of concentration differences for ions with the development of the blood-brain barrier to macromolecules we wanted to evaluate an eventual relationship between the development of these two functions of the blood-brain barrier.3. The concentration of protein in cerebrospinal fluid and plasma was measured in foetal, juvenile and adult rabbits and in new-born, juvenile and adult rats. The concentration of protein was similar in rabbit foetuses at 23 days of gestational age (term at 31 days) and in new-born rats, and the ratio decreases at approximately the same rate in the two species.4. The high concentration of proteins in cerebrospinal fluid might reflect either a high rate of entry of protein into the brain or a low production rate of cerebrospinal fluid. Injection of Diamox(R) (100 mg/kg) 2 hr before sampling of cerebrospinal fluid did not change the concentration of protein in cerebrospinal fluid in new-born rats whereas it increased the concentration in older rats. This finding suggests that new-born rat produces little (if any) cerebrospinal fluid suggesting that the high concentration of protein in cerebrospinal fluid in new-born rats reflect a low rate of turnover of cerebrospinal fluid.5. The concentration of sodium, potassium, chloride and magnesium in plasma and cisternal cerebrospinal fluid was measured in rabbits of different age, from 23 days of gestation until adulthood, and in rats of different ages from birth until adulthood.6. Concentration differences between plasma and cerebrospinal fluid for these were established in the youngest animals examined, indicating that the active transport mechanisms for these ions were functioning at an age where the concentration of protein in cerebrospinal fluid was very high.7. The maintenance of concentration differences for ions at a time where the concentration of proteins in cerebrospinal fluid is high, is difficult to explain if the high concentration of proteins in cerebrospinal fluid is due to a leakiness of the intercellular junctions between cerebral endothelial cells. However, the findings might be explained either by a low rate of production of cerebrospinal fluid in the youngest animals and/or by a pinocytotic transfer of proteins across the blood-brain barrier in these animals.8. In rats concentration gradients for ions are established at an age (new-borns) with a low or absent bulk formation of cerebrospinal fluid and at an age where the capillaries are still not enveloped by astrocytic foot processes. These facts suggest that the active transport mechanisms for the ions must be located in the cerebral endothelial cells.     

Plasma and cerebrospinal fluid vasopressin and osmolality in relation to thirst

Conscious dogs chronically implanted with a device for cerebrospinal fluid (CSF) sampling from the anterior 3rd ventricle were submitted to 24 h dehydration. During rehydration by drinking the total water intake (TWI) after 16 min was determined in 8 and after 90 min in 14 experiments. Samples were simultaneously drawn to determine the osmolalities (P_osm, CSF_osm) and AVP concentrations (P_VVP, CSF_AVP) of plasma and CSF. After 24 h dehydration all of these parameters were significantly elevated in comparison to euhydrated dogs investigated on 19 occasions. In 8 experiments 60% of the final TWI had been ingested within the first 16 min with no changes of P_osm, CSF_osm and CSF_AVP, but a significant decrease of P_AVP at this time. TWI per kg body weight (TWI·kg^–1) after 90 min was significantly correlated with the osmolalities and AVP levels in plasma and CSF prior to rehydration. The decreases of P_osm, CSF_osm and P_AVP, but not of CSF_AVP, were significantly correlated with TWI·kg^–1. The results indicate that P_AVP and CSF_AVP are subject to long term control by body fluid tonicity exhibiting a feedback relationship to water intake. In addition, P_AVP but not CSF_AVP seems to be under short term, possibly nonosmotic, control during water intake.Supported by the Alexander von Humboldt-Foundation     

Regulation of angiotensinogen in cerebrospinal fluid and plasma of rats

The origin and regulation of angiotensinogen in cerebrospinal fluid (CSF) was investigated in rats by measuring renin substrate in plasma and CSF under different experimental conditions. Nephrectomy (NX) increased the circulating and the central angiotensinogen levels. There was no correlation between the individual values of plasma and CSF. Adrenalectomy (ADX) diminished and hydrocortisone treatment augmented the angiotensinogen levels in plasma and CSF. The combination of ADX and NX caused a dissociation between peripheral and central angiotensinogen, since the values were elevated in plasma but unchanged in CSF. After the application of the converting-enzyme inhibitor captopril a significant decrease of angiotensinogen was observed in plasma only. A specific radioimmunoassay for renin substrate of rat plasma also recognized CSF angiotensinogen. There was a linear correlation between the CSF substrate levels obtained by direct and indirect measurement. In conclusion, CSF angiotensinogen appears to be immunologically similar to the plasma molecule. The angiotensinogen levels in CSF and plasma may be affected in parallel but can nevertheless be dissociated from each other.     

Relationship between the occurrence of virus in plasma and cerebrospinal fluid of HIV-1 infected individuals

Attempts to isolate human immunodeficiency virus type 1 (HIV-1) were carried out on cerebrospinal fluid (CSF) and blood plasma samples from 111 HIV-1 infected subjects in various stages of infection. HIV-1 was recovered at a low rate from CSF of persons with normal immunological parameters but frequently from patients with abnormal values, in all stages of immune system involvement. Isolation from plasma was positive in the majority of the patients, in all stages of infection, with a frequency that was related to the degree of immunodeficiency. HIV-1 could be recovered from the CSF of most patients (74%) with viremia when 85 paired specimens of 58 patients were analyzed. By contrast, HIV-1 was isolated from CSF, but not from plasma, in one case only. HIV-1 p24 antigen measured by an enzyme-linked immunosorbent assay (ELISA) was detectable in only four CSF samples compared with 15 serum samples in paired specimens. These findings indicate that most patients with HIV-1 infection have circulating cell-free infectious virus in the blood and simultaneously demonstrable HIV-1 in the CSF. Replication of HIV-1 exclusively in the central nervous system (CNS) appears to be a rare event.     

Interrelations between cerebrospinal fluid and plasma inorganic ions and glucose in patients with chronic renal failure.

The concentrations of inorganic ions and glucose in the plasma and CSF of 11 patients with "steady-state" chronic renal failure have been measured and their CSF: plasma interrelations studied. The results have been compared with the corresponding data from 34 control subjects. In the patients with renal failure, there was a positive correlation between raised CSF and plasma potassium concentrations. In contrast to the impaired potassium homeostasis, normal CSF magnesium and calcium concentrations were observed despite wide variations in the plasma concentrations of these ions.     

The relationship of cerebrospinal fluid and plasma theophylline concentrations in children and adolescents taking theophylline

Ten ambulatory subjects with asthma experienced a seizure while they were receiving oral theophylline preparations and were evaluated prospectively according to a set protocol. The protocol included a lumbar puncture that permitted the simultaneous determination of plasma and cerebrospinal fluid (CSF) theophylline concentrations. A constant relationship was observed between the plasma theophylline concentration and that of the CSF. It was found that the theophylline concentrations in these two biologic fluids could be characterized by the regression equation y = 0.41 X + 0.7 where y is the CSF theophylline concentration and X is the plasma theophylline concentration. Two infants with hydrocephalus treated by ventriculoperitoneal shunt were also simultaneously evaluated for plasma and CSF theophylline concentrations. These infants demonstrated greater than expected entry of theophylline into the CSF. Some central nervous system abnormalities may be characterized by increased theophylline entry into the CSF.