Marinobufagenin levels in preeclamptic patients: a preliminary report

Preeclampsia is a disorder resulting in significant fetomaternal complications with no definitive pharmacological intervention. A bufadienolide, marinobufagenin, has been implicated in the etiology of preeclampsia. We investigated both the blood and urine levels of marinobufagenin in preeclamptic and control subjects. Preeclamptic and normotensive pregnant women were recruited at various gestational age periods. Blood and urine specimens were obtained and analyzed for marinobufagenin levels and creatinine. The former determination was performed utilizing a new, novel chemifluorescent enzyme-linked immunosorbent assay. The marinobufagenin levels were higher in preeclamptics than in the controls in both serum and urine at various gestational age periods. Additionally, the mean level of marinobufagenin in the preeclamptic group was significantly greater than in controls in both blood and urine specimens ( P?相似文献   

Role of primate basal ganglia and frontal cortex in the internal generation of movements

In order to more comprehensively assess the role of the basal ganglia in the internal generation of movements, we studied the activity of neurons in the head of the caudate and in the rostral putamen in relation to the execution of movements. Monkeys performed self-initiated and stimulus-triggered arm reaching movements in separate blocks of trials. With stimulus-triggered movements, 217 striatal neurons increased their activity after the trigger stimulus (127 in caudate, 90 in putamen). Of these, 68 neurons showed time-locked responses to the trigger stimulus, with a median latency of 60 ms, that were independent of visual or auditory stimulus modalities. Three quarters of responses were conditional on a movement being performed. These responses may participate in neuronal processes through which the reception of a stimulus is translated into the execution of a behavioral reaction. Further, 44 neurons increased their activity before the earliest muscle activity without being clearly time-locked to the stimulus (148-324 ms before movement onset), 55 neurons were activated later before the movement, and 50 neurons were activated after movement onset. With self-initiated movements, 106 striatal neurons showed movement-related activity beginning up to 460 ms before movement onset (52 in caudate, 54 in putamen). Comparisons between the two types of movement were made on 53 neurons with premovement activity beginning more than 500 ms before self-initiated movements. Only one fifth of them also showed movement-related activity with stimulus-triggered movements, including trigger responses. Comparisons among 39 neurons with movement-related activity during self-initiated arm movements showed that about half of them also showed movement-related activity with stimulus-triggered movements. These data demonstrate a considerably segregated population of striatal neurons engaged in the internal generation of movements, whereas processes underlying the execution of movements appear to involve overlapping neuronal populations.     

Responses of nigrostriatal dopamine neurons to high-intensity somatosensory stimulation in the anesthetized monkey

Nigrostriatal dopamine (DA) neurons of the mammalian midbrain play an important role in behavioral reactions. Their destruction in Parkinsonian patients and experimentally lesioned animals leads to a reduction and slowing of movements as well as other motor, cognitive, and motivational deficits. We tested the responses of DA neurons to somatosensory stimulation to gain insight into the nature of peripheral information reaching these neurons. Experiments were performed as repeated sessions in two anesthetized monkeys having chronically implanted recording chambers, thereby reducing the number of primates required for experimentation. Midbrain DA neurons were characterized by their histological location, by the form, duration, and frequency of extracellularly recorded, spontaneously occurring impulses, by antidromic activation from caudate and putamen, and by the reduction of impulse rate following systemic administration of low doses of the DA autoreceptor agonist apomorphine. Half of the midbrain DA neurons (65 of 145 neurons, 45%) were antidromically activated from chronically implanted stimulating electrodes in caudate (35 neurons), putamen (47 neurons), or both structures (17 of them). Conduction velocities ranged from 0.7 to 2.5 m/s, with medians of 1.2 and 1.5 m/s for neurons projecting to caudate and putamen, respectively. Half of the midbrain DA neurons were depressed (72 of 140 neurons, 51%) and less than a quarter activated (24 of 140 neurons, 17%) by intense noxious pinch stimulation to the body surface. Innocuous, even intense, surface or deep somatosensory stimuli were ineffective. Pinch responses continued during the whole stimulating period of several seconds in most DA neurons. There was no response habituation during repeated stimulation. Convergence between spinal and trigeminal input and from both body sides was seen for virtually all noxious pinch responses. Thus DA neurons typically responded in the same direction to pinch stimulation of hand, foot, face, tail, and dorsum of both sides. Systemic administration of the DA receptor antagonist haloperidol (0.33 or 0.50 mg/kg) strongly reduced pinch responses in all seven DA neurons tested. This provides evidence for an involvement of DAergic neurotransmission in the representation of exteroceptive input in the brain. The results show that midbrain DA neurons projecting to the striatum respond to noxious somatosensory input in the anesthetized monkey. The bilateral nontopographic nature of the responses does not support a role in precise stimulus recognition, rather it suggests a mechanism involved in basic neuronal processes underlying behavioral responsiveness.     

The Helsinki Heart Study: central findings and clinical implications

This paper describes the central findings and discusses the clinical implications of the Helsinki Heart Study. This was a controlled primary prevention trial to test the hypothesis that using gemfibrozil to lower the concentrations of serum low density lipoprotein (LDL) and very low density lipoprotein (VLDL) and to raise that of high density lipoprotein (HDL) protects subjects against coronary heart disease.     

Guided coronary atherectomy: preliminary results]

Coronary atherectomy implies removing atheromatous material from the diseased coronary arterial wall. This technique has emerged as an attractive alternative to conventional percutaneous transluminal coronary angioplasty procedures, in an attempt to diminish both initial procedural failure and restenosis rate. Among different technologies, the Simpson's atherotome provides a means of performing directional (i.e. selective) coronary atherectomy (DCA). This device implements a coaxial catheter which is advanced into the lesion over a steerable guidewire. Its distal tip includes a hollow metallic cylinder with a lateral window. Removal of the material is accomplished by a rotating cutter which can be moved distally, once the device's window has been orientated facing the lesion. We have performed 14 DCA in 14 patients. Mean age was 58 years and 12 patients were male. The technique was indicated for unstable angina (7 patients), stable angina (4 patients) and silent myocardial ischemia (3 patients). Fifteen lesions were attempted (13 original and two with restenosis), located as follows: nine in the left anterior descending coronary artery, three in the right coronary artery and three in the left circumflex artery. Eleven lesions were proximal and four were located in mid coronary segments. Twelve lesions (80%) were eccentric, and five (33%) were irregular. Initial angiographic success (residual stenosis less than 50%) was obtained in all 15 lesions (100%). Pre-DCA stenosis was 84 +/- 5% and post-DCA stenosis was 16 +/- 6%. There was no need for urgent coronary artery by-pass surgery and no patient developed an acute myocardial infarction in relation to the procedure. A 82-year-old woman died after the procedure in cardiogenic shock.(ABSTRACT TRUNCATED AT 250 WORDS)     

Deficits in reaction times and movement times as correlates of hypokinesia in monkeys with MPTP-induced striatal dopamine depletion

1. We quantitatively assessed deficits in the initiation and execution of arm movements occurring after destruction of nigrostriatal dopamine neurons by systemic administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) (Sigma). Three monkeys performed a reaction time task in which they reached toward a single and constant target for food reward. 2. After administration of MPTP, all three monkeys showed hypokinesia necessitating dopamine precursor or receptor agonist treatment. The partial recovery of one animal from initial akinesia after 19 days permitted discontinuation of dopaminergic drug therapy, although marked hypokinesia remained present. The two other animals displayed additional, intermittent phases of rigidity and activation tremor and needed continuous dopaminergic drug therapy for most of the postlesion period. 3. Administration of MPTP significantly prolonged EMG reaction time in prime mover muscles and arm movement reaction time by 47-225% and 18-129%, respectively, on the six sides of the three animals, compared with control measurements before the lesion. EMG and arm movement reaction time increased over consecutive trials in most sessions comprising 110-130 movements, the first 20 movements showing almost normal values. The delay time between onsets of EMG and arm movement showed unsystematic changes. These deficits in movement initiation were observed both with and without dopamine precursor therapy. They lasted during the whole testing period of several months. 4. Linear correlations between arm movement onset and EMG onset in the two prime mover muscles, the extensor digitorum communis and the biceps, showed coefficients of mostly 0.7-0.9, both before and after MPTP. These data suggest that the temporal relationship between onsets of arm movement and EMG were not substantially affected by MPTP. 5. Arm movement time was divided into two phases. The duration of movement between the resting key and the target, a small food-containing box located ahead of the animal, was denoted as reaching movement time. The following hand manipulation inside the food box was measured as box movement time. After MPTP, both measures were significantly prolonged by 10-103% and 12-251%, respectively, on the six sides of the three monkeys. These deficits in movement execution were observed both with and without dopaminergic drug therapy and during the whole testing period. 6. Task performance after MPTP treatment was studied in one monkey in the absence of dopaminergic drug therapy. EMG and arm movement reaction times recovered partially over several weeks, while the prolongations in reaching and box movement times remained unchanged.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prolonged changes in dopaminergic terminal excitability and short changes in dopaminergic neuron discharge rate after short peripheral stimulation in monkey

Time-courses of responses to peripheral somatosensory stimulation were studied in the nigrostriatal dopamine (DA) system by comparing rates of neuronal discharges with changes in nerve terminal excitability, an indicator of DA release. The excitability of DA nerve terminals in the putamen was assessed as probability for evoking an antidromic response in substantia nigra DA cells with electrical stimulation in an anesthetized monkey. At about 30-60% decrease of excitability was seen during and about 15 min beyond pain pinch stimulation (PPS) in 12 of 17 tested DA neurons, while 4 neurons showed a 40% increase. Discharge rates were decreased in 7 and increased in 5 of the 17 DA neurons during, but not after PPS. It is concluded that the release of DA in the striatum may be controlled in two ways: rapid reactions would be mediated by changes in discharge rate, while slower, prolonged responses could be due to presynaptic interactions with other striatal afferents.