Movement-related potential measures of different modes of movement selection in Parkinson's disease

Movement-related potentials were recorded preceding self-paced voluntary movements in patients with Parkinson's disease and in healthy subjects of the same age group. We compared the Readiness Potential preceding joystick movements in a fixed direction and preceding joystick movements in freely selected directions. In normal subjects the Readiness Potential amplitude was higher preceding freely selected movements than preceding movements in a fixed direction. The Readiness Potential in Parkinson patients failed to be modified by the different modes of movement selection. The modulation of the Readiness Potential by different ways of preparing for movement might be due to the supplementary motor area (SMA) being more strongly engaged by tasks requiring internal control of movements than by tasks that are externally structured. The results suggest that this task-dependent variation of SMA activity is reduced in Parkinson's disease. A failing capacity to adapt SMA activity to different task demands has previously been suggested by evidence from positron emission tomography studies using similar tasks.     

Clinical efficacy of Sinemet CR 50/200 versus Sinemet 25/100 in patients with fluctuating Parkinson's disease. An open, and a double-blind, double-dummy, multicenter treatment evaluation. The Dutch Sinemet CR Study Group.

In a multicenter study we selected 84 patients with fluctuating Parkinson's disease in order to evaluate the effects of controlled-release Sinemet 50/200 (=CR) versus standard Sinemet 25/100 (=STD) in an open-label 8-week titration period, followed by a double-blind, double-dummy 24-week treatment period. In contrast with previous double-blind studies, the efficacy of Sinemet CR proved to be significantly superior to that of Sinemet-STD according to NYUPDS and NUDS rating scales. This higher efficacy of Sinemet CR was not achieved at the expense of safety and/or tolerability. Actual total daily levodopa dosage in patients treated with Sinemet CR was increased by 33%; however, the plasma level of this dosage is calculated to be similar to that of the previous dosage of Sinemet-STD (bio-availability of Sinemet CR is 71%). Mean numbers of daily doses, off-hours, and off-periods were decreased significantly during Sinemet CR treatment. Although all other variables suggest that the number of on-hours had to be increased, statistical significance could not be reached in this respect.     

硫酸多糖对体外人脐静脉内皮细胞损伤的保护作用

研究表明,硫酸多糖体外对多聚阳离子和氧自由基损伤的人脐静脉内皮细胞有保护作用。肝素、硫酸软骨素A抗多聚阳离子损伤作用比同浓度低分子肝素和甘糖酯强。肝素、硫酸软骨素A、甘糖酯抗氧自由基损伤作用优于同浓度低分子肝素。结果显示硫酸多糖有保护血管内皮的作用,其作用可能与所带阴离子基团有关。     

Movement-related potentials preceding voluntary movement are modulated by the mode of movement selection

In two experiments movement-related cortical potentials preceding voluntary movement were recorded. In experiment 1, subjects performed four motor tasks involving joystick movements. The four tasks differed in complexity (single vs sequential movements) and in the mode of movement selection, i.e., whether a movement or movement sequence was made in fixed or in self-determined directions. The choice of these tasks was based, firstly, on previous electrophysiological studies suggesting an effect of task-complexity on the amplitude of the readiness potential (RP) and, secondly, on previous positron emission tomography (PET) studies showing that activity of the supplementary motor area (SMA) is influenced by the mode of movement selection. The results show that, for single movements, RP amplitude is higher preceding freely selected movements than preceding movements in a fixed direction. In experiment 2 this effect was replicated using button presses instead of joystick movements. The results converge with PET evidence obtained in similar tasks and establish that the RP is modulated by the mode of movement selection. This modulation is probably related to differential involvement of the SMA.     

Protective cytotoxic T lymphocyte responses against paramyxoviruses induced by epitope-based DNA vaccines: involvement of IFN-gamma

Plasmid DNA vectors have been constructed with minigenes encoding a single cytotoxic T lymphocyte (CTL) epitope from either the M2 protein of respiratory syncytial virus (RSV) or from the nucleoprotein of measles virus (MV) with or without a signal sequence (also called secretory or leader sequence). Following intradermal immunization, plasmids in which the CTL epitopes were expressed in-frame with the signal sequence were more effective at inducing peptide- and virus- specific CTL responses than plasmids expressing CTL epitopes without the signal sequence. This immunization resulted in protection against MV-induced encephalitis and a significant reduction in viral load following RSV challenge. The reduction of viral load following RSV challenge was abrogated by prior injection with anti-IFN-gamma antibodies. These results highlight the ability of epitope-based DNA immunization to induce protective immune responses to well-defined epitopes and indicate the potential of this approach for the development of vaccines against infectious diseases.      

Relationship between memory strategies and motor symptoms in Parkinson's disease

Patients with Parkinson's disease(PD) show a serious decrease in performance on tasks which lack explicit guidelines and which necessitate the subject to develop his or her own strategy. Using the California Verbal Learning Task(CVLT) we have found evidence that this phenomenon becomes also manifest in learning and memory. The goal of the present study on PD was to investigate whether or not there is an intrinsic relationship between PD-specific deviant learning characteristics and the severity of motor symptomatology. The results show, as expected, a significant correlation between the severity of bradykinetic/hypokinetic symptoms and the serial clustering gradient of the CVLT: the more bradykinetic PD patients (n = 48) were, the more they were dependent on the externally guided serial learning strategy. The findings are discussed in the context of our hypothesis that the actual deficit in patients with PD is a deficient processing of ambiguous internal cues.     

Decreased striatal dopamine-receptor binding in sporadic ALS: glutamate hyperactivity?

The pathogenesis of ALS may be related to increased glutamatergic excitotoxicity. The striatum receives massive glutamatergic input. Animal studies suggest that glutamate decreases striatal D2-receptor synthesis. In drug-naive, sporadic ALS patients we demonstrated decreased striatal D2-receptor binding in vivo that could be partially reversed by the glutamatergic transmission blocker riluzole. Our findings support the glutamatergic excitotoxicity hypothesis in sporadic ALS.     

Effects of female sex steroids on Parkinson's disease in postmenopausal women

There are conflicting reports about estrogen modulating the activity of nigrostriatal dopaminergic neurons. Furthermore, modulation may be influenced by progesterone levels. Therefore, the clinical effects of sex steroids on parkinsonian symptoms in postmenopausal women with Parkinson's disease (PD) were analyzed in the present study. Patients (n = 12) were under the age of 80, able to perform the motor function tests, and showed no contraindications for estrogen suppletion. Motor function was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and a patient interview on subjective changes. In a placebo-controlled, randomized, double-blind trial lasting 8 weeks, no significant dopaminergic effect of estradiol (E2) could be demonstrated, whereas in an open trial phase lasting 2 weeks, progesterone seemed to have an antidopaminergic effect. Several mechanisms are discussed that can account for the fact that we found no effect of E2 on motor functioning in our patients with PD.     

Decreased striatal dopamine D2 receptor binding in amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA): D2 receptor down-regulation versus striatal cell degeneration

Recently, decreased striatal dopamine D2-receptor binding was demonstrated in vivo in amyotrophic lateral sclerosis (ALS). To further elucidate the pathogenetic mechanism underlying this D2-receptor deficit, a multi-level comparison was made between 30 sporadic ALS subjects and 24 patients with multiple system atrophy (MSA), a disorder clinically characterized by bradykinesia, neuroradiologically by severe D2-receptor loss, and neuropathologically by degenerating striatal cells. The extent of D2-deficit in ALS and MSA were within the same range, but extrapyramidal signs and symptoms were virtually absent in our ALS patients. Striatal cell loss in general or competitive D2-receptor occupancy could be considered unlikely in ALS. The striatum receives massive glutamatergic input and the pathogenesis of ALS may be related to increased glutamatergic excitotoxicity. As other mechanisms (cell loss, receptor occupancy) could be ruled out, and as animal studies suggest that (excess of) glutamate decreases striatal D2-receptor synthesis, the striatal D2-receptor deficit in ALS is most likely to be caused by a receptor down-regulation.     

Human ovarian granulosa cells and follicular fluid indices: the relationship to oocyte maturity and fertilization in vitro

The study investigates the correlation between oocyte maturity and fertilization and a variety of hormonal parameters in follicular fluid and ovarian granulosa cells. A methodology for purification of granulosa cells from contaminating blood cells is also established. A total of 63 follicular aspirates were collected at oocyte retrieval from 30 women superovulated using the long luteinizing hormone- releasing hormone (LHRH analogue)/human menopausal gonadotrophin regimen. Oestradiol, progesterone, testosterone and human chorionic gonadotrophin (HCG) were quantified in follicular fluid and granulosa cells were immunostained for human chorionic gonadotrophin. Immunopurification of granulosa cells from contaminating blood cells was performed. HCG in follicular fluid was significantly high in follicles yielding immature (grade 3) oocytes (P=0.002); there was no correlation with fertilization. Aspirates from follicles containing mature (grade 1) oocytes and oocytes that subsequently fertilized had significantly more granulosa cells immunobound to HCG (P < 0.001, P=0.02). Moreover, the immunomagnetic purification technique provided >98% pure population of granulosa cells. The data demonstrate that HCG in follicular fluid and on granulosa cells may help to predict oocyte maturity and fertilization. Furthermore, immunomagnetic beads provide a reliable procedure for the purification of ovarian granulosa cells.