Homocysteine levels after acute levodopa intake in patients with Parkinson's disease

Levodopa (L ‐dopa) administered with a dopadecarboxylase inhibitor (DDI) increases homocysteine plasma levels. This may support the onset of atherosclerosis‐related disorders and neuropsychiatric complications in patients with Parkinson's disease (PD). This homocysteine elevation is considered as long‐term effect of chronic L ‐dopa/DDI treatment. Little is known about the acute effects of L ‐dopa/DDI intake on homocysteine generation. The objective of this trial was to investigate the relations between L ‐dopa and homocysteine after acute L ‐dopa/DDI administration in PD patients with different L ‐dopa metabolism. Thirty PD patients were divided into groups with superior (I) and less (II) L ‐dopa absorption after standardized intake of 125 mg L ‐dopa/benserazide with determination of L ‐dopa, 3‐O‐methyl‐dopa (3‐OMD) and homocysteine in plasma at baseline, 30, 60, and 90 minutes. There was a homocysteine increase in Group I (F = 5; P = 0.005) and a moderate decrease in Group II (F = 4.27; P = 0.01). A rise of 3‐OMD (F = 10.51; P < 0.0001) appeared in Group I, but not in Group II (F = 0.91; P = 0.44), accordingly L ‐dopa accumulation was better in Group I than in Group II. Thus, in conclusion, L ‐dopa metabolism is an important component for homocysteine elevation after one time L ‐dopa/DDI administration in PD patients. © 2009 Movement Disorder Society     

Relationship between weight, levodopa and dyskinesia: the significance of levodopa dose per kilogram body weight

Purpose:  Levodopa dose per kilogram body weight is reported to be a significant factor for dyskinesia in Parkinson's disease. We have investigated this hypothesis in data from the studies comparing ropinirole versus levodopa as the initial therapy.
Methods:  Data from the ropinirole versus levodopa studies 056 and REAL-PET in early Parkinson's disease were pooled and manipulated to calculate levodopa dose per kilogram body weight. Logistic regression analysis was performed to investigate significant variables for the development of dyskinesia. Only the patients on levodopa monotherapy or with ropinirole were analyzed.
Results:  Analysis of levodopa therapy patients revealed that dyskinetic patients had received significantly higher absolute levodopa dose and levodopa dose per kilogram body weight. Logistic regression revealed that the most significant factor was the higher levodopa dose per kilogram body weight, P  = 0.005, odds ratio 1.078, 95% CI 1.023–1.135; younger age was the second factor – P  = 0.026. Variables of gender, absolute levodopa dose, weight, disease duration and initial motor Unified Parkinson's disease rating score were not significant.
Conclusion:  Higher levodopa dose per kilogram body weight is an independently significant factor for developing dyskinesia. This relationship should be considered in treatment of Parkinson's disease patients aiming to prevent and manage dyskinesia.     

Delay of simple reaction time after levodopa intake.

BACKGROUND: Parkinsonian patients (PP) have deficits in the preparation and execution of movements. It is generally accepted that PP show delayed performance of simple reaction time (SRT) paradigms due to impaired response preprogramming. To date, no trial considered putative effects of dopaminergic substitution on SRT performance in PP. OBJECTIVES: To determine short-term effects of acute levodopa intake and impact of long-term dopaminergic substitution on the results of a SRT task. METHODS: We repeatedly performed a SRT paradigm in previously untreated- and treated PP, taken off medication for at least 12 h, before and after intake of levodopa/benserazide and in PP, who received placebo. RESULTS: Reaction time significantly increased and movement time did not change after levodopa intake. Placebo application showed no effects. CONCLUSIONS: Levodopa delayed cognitive processing and/or behaviour. Sedative effects of levodopa and/or dopamine overflow in prefrontal regions with subsequent cholinergic dysfunction hypothetically caused this phenomenon.     

Investigating the relationship between plasma neuropeptide-S levels and clinical depression

Purpose: Neuropeptide-S (NPS) is a novel 20-amino acid peptide, mainly expressed in the central nervous system and endocrine tissues. NPS has been linked to anxiety and fear-related behaviors. The association of NPS with depression in a human population has not been previously examined. The aim of the current study was to explore the potential association of NPS with clinical depression and comorbid anxiety.

Materials and methods: Seventy-nine patients diagnosed with major depressive disorder and seventy-eight controls were included in the study. The Hamilton Depression Scale (HAM-D) and Hamilton Anxiety Scale (HAM-A) were used to measure depression and anxiety levels, respectively. Venous blood samples were obtained to measure plasma NPS levels.

Results: There were no statistically significant differences between the patients and controls in terms of sex, marital status, and smoking status. Plasma NPS levels were also not significantly different between the patients and controls. In patients with major depressive disorder, HAM-A and HAM-D scores were significantly higher than those of controls. No correlation was found between plasma NPS levels and age, body mass index (BMI), median HAM-A scores, and median HAM-D scores.

Conclusions: Despite a significantly high level of comorbid anxiety among the patient group, we found no relationship between plasma NPS levels and depressive symptomatology.     

The relationship between cholesterol levels and depression in the elderly

OBJECTIVE: This study was undertaken to evaluate the possible association between low levels of serum cholesterol and depression in the elderly. BACKGROUND: The alteration of cholesterol content of synoptosomal membrane in response to low serum cholesterol levels has been shown to decrease the serotonin receptors in depressed patients. Previous studies suggest that low levels of serum cholesterol may be associated with the increased risk of depression in the elderly. SUBJECTS AND METHODS: This was a cross-sectional study where 189 subjects over 65 years old of both sexes were enrolled. Serum total cholesterol, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglycerides were measured. Cognitive functions were evaluated with mini mental state examination survey (MMSES) and depression was assessed with Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). RESULTS: Of the 189 subjects, 42 were affected by depression. Low serum cholesterol level (cut-off < or =160 mg/dl) as well as the levels of HDL-C, LDL-C and triglycerides were not associated with depression in older men or women. CONCLUSIONS: In the present cross sectional study, there was no association between depression and low serum cholesterol levels after adjusted for confounding factors. Further studies are needed to clarify this suggestion with larger number of patients.     

The relationship between sleep patterns and attention levels

Fifty-nine adults slept five nights with an Actigraph and answered two questionnaires related to sleeping quality and morningness/eveningness preferences. Next they performed a computerized attention task (the mathematics continuous performance test (MATH-CPT)) to assess various measures of attention. Results showed significant correlations between six attention variables and two measures of sleep assessed by the Actigraph. Linear regression with sleep variables as independent variables, and measures of the computerized test as dependent variables showed that sleep measures explained 30% of the variance of the score in the “final attention formula” of the test, and 27% of the “rate of response.”     

细胞因子水平与癫痫发作关系的研究进展

癫痫是神经系统常见疾病，发病率为1％，全世界约5000万患者，我国目前约有900万患者。约60％-70％患者通过药物可以控制，30％以上属难治性癫痫，约7％～8％可进行外科治疗，还有大约25％患者目前无有效治疗，因此，从发病机制着手研究探寻新的有效治疗手段仍是当今癫痫研究的重点。癫痫的病因和病理机制非常复杂，近年来越来越多的科学工作者对癫痫的发病机制及治疗研究进一步深入，目前公认癫痫的发病机制的研究方向丰要旬括以下五方面     

Clinical perspectives on the relationship between pain and disability

Physicians involved in the evaluation and management of those with pain as a primary symptom are frequently requested to provide information about the "disability status" of that individual. Such requests arise from third-party payors such as insurance companies, state workers compensation departments, and other systems of disability determination. To effectively manage the individual with pain, the physician needs to have an understanding of the concepts of disability and those systems involved in this process.     

Acute levodopa intake and associated cortisol decrease in patients with Parkinson disease

Levodopa application improves motor symptoms in patients with Parkinson disease (PD). Levodopa induces lower cortisol plasma levels and decreases serotonergic activity in certain brain areas of fish. The objectives of this study were to perform repeat cortisol concentration measurements before and after the administration of soluble levodopa/benserazide (dose, 200 mg) in 32 patients with PD during an interval of 150 minutes. The cortisol concentrations significantly decreased after levodopa intake, particularly in the patients with more advanced stage of PD, but not in the less affected patients. There were significantly lower cortisol levels in the patients at the advanced stage of PD compared with those of the earlier patients with PD, particularly at -30, 0, and 90 minutes before/after levodopa application. Significant inverse relations were found between the cortisol levels and the Unified Parkinson Disease Rating Scale total score, particularly at 60 and 90 minutes after levodopa intake. Neurodegeneration occurs in striatal regions and in the brain stem of patients with PD. The 5-HT-containing neuronal terminals of the brain stem hypothetically mediate the cortisol level decrease after levodopa intake because these cells contain an important fraction of amino acid decarboxylase. Therefore, this compartment may be the site of enzymatic conversion of superfluous, exogenous levodopa to dopamine. Consequently, short-term levodopa administration also leads to levodopa uptake in these 5-HT-metabolizing neurons, which interferes with the 5-HT synthesis and may cause a decrease of 5-HT levels. These lower 5-HT levels reduce the hypothalamic function and, via the corticotropin axis, the subsequent peripheral cortisol release. Thus, levodopa-induced cortisol decrease may be related to PD progression.     

脑血管病患者血浆中同型半胱氨酸的丰度及相关性研究

目的研究血浆中同型半胱氨酸（Hcy）的丰度在脑血管病患者中的分布及变化,观察它与脑血管病发生及其他相关危险因素间的关系。方法收集257例经临床及影像学确诊的脑血管病（包括脑梗死、脑出血、短暂性脑缺血发作）患者的临床资料,对其血浆Hcy水平与脑血管病发生及其他危险因素进行相关性研究,数据用SPSS13.0统计软件分析。结果脑梗死、脑出血、短暂性脑缺血发作（TIA）三组的Hcy水平明显高于正常对照组,高血压病、高脂血症与Hcy水平呈正相关,高Hcy血症与脑血管病发生呈显著正相关。结论高Hcy血症与脑血管病发生有关,是脑血管病的独立危险因素。     

Clinical experience with the novel levodopa formulation entacapone + levodopa + carbidopa (Stalevo)

Levodopa is the main pharmacologic treatment for Parkinson's disease. However, the long-term administration of levodopa is associated with the development of motor complications which can seriously compromise patient function. Increasing evidence indicates that such problems are related to abnormal pulsatile stimulation of striatal dopamine receptors and that treatments providing more continuous stimulation reduce the risk of motor complications. It is possible that administering levodopa with a reversible catechol-O-methyl transferase inhibitor at frequent intervals might reduce the risk of these complications. Stalevo (Orion) combines levodopa, the dopa-decarboxylase inhibitor carbidopa and the catechol-O-methyl transferase inhibitor entacapone in a single tablet. This review provides an overview of the initial clinical experience gained with Stalevo during clinical trials, including several case studies.     

The relationship between haloperidol blood levels and clinical responses

Haloperidol blood levels in patients were determined to elucidate the relationship between blood levels and clinical effects. Determinations of haloperidol serum were performed by radioimmunoassay and the clinical status was estimated using BPRS. The relationship between haloperidol serum levels and BPRS total score was studied in 20 chronic schizophrenics currently receiving haloperidol treatment. The results did not show positive relationship between these two. Another 11 schizophrenic patients were treated with daily doses of average 6 mg of haloperidol. The patients were classified into improved and unchanged group according to the changes of BPRS total score. All 7 cases classified into the improved group had short duration of the illness less than one year. In this group, the levels were lower initially but gradually rised in paralled with the increase of extent of recovery on BPRS. Furthermore, improvement of psychopathology by means of decrease of BPRS total score was still found after haloperidol serum levels reached a plateau. The results did not support the view that high blood concentration of haloperidol might contribute to the clinical effects, but still suggested utility of measuring blood levels in acute or subacute patients being treated with haloperidol medications.     

血浆同型半胱氨酸水平与急性脑梗死关系探讨

目的 探讨血浆同型半胱氨酸(Hcy)水平与急性脑梗死的关系.方法 选择急性脑梗死患者80例为观察组,选取与之年龄、性别相匹配的同期我院健康体检者60例为对照组.所有入选者均清晨空腹抽取静脉血8 mL,分别送检血生化、叶酸(FA)、维生素B12 (VitB12)及血浆Hcy水平.结果 观察组血浆Hcy水平显著高于对照组(P＜0.01).观察组血浆Hcy水平与FA及VitB12水平均呈负相关.条件Logistic回归模型检验发现高Hcy血症的OR值5.268(95％ CI2.405～11.542).结论 高Hcy血症可能是急性脑梗死的独立危险因素.     

The relationship between metal ion levels and biogenic amine levels in epileptic mice

The metabolism of various metal ions and biogenic amines in El mice, an inbred mutant strain susceptible to epilepsy, was investigated as a possible model for seizure mechanism. Serum Na, P, Ca, Mg, Fe and Zn levels in El mice were lower than those in ddY mice, the mother strain of El mice. Conversely, bone Ca, P, Na, Mg and Zn levels in El mice were higher than those in ddY mice. The results obtained by chemical analysis are consistent with radiographic observations. Possible mechanisms for the lower serum metal ion levels seen in El mice include a decrease in availability of these ions from bone. The dopamine (DA) level in El mouse brain was 15% lower than in ddY mice but could be raised by intraventricular administration of CaCl₂. This result was supported a decreased ethanol-induced sleeping time in El as compared to ddy mice, with ‘normalization’ occurring after intraventricular administration of DA or CaCl₂. The biogenic amine levels disorder in El mice is discussed on the basis of our pharmacological observation that biogenic amine synthesis is regulated by divalent cations via a calmodulin-dependent system. Our results suggest that the disorders of metal ion metabolism could be a mechanism for epileptic convulsions in El mice.     

Clinical significance of the interaction between lithium and a neuromuscular blocker

Reports of delayed recovery from anesthesia by patients concurrently receiving lithium carbonate and a neuromuscular blocker have been followed by a recommendation to avoid such a combination and, hence, concurrent treatment with lithium and electroconvulsive therapy (ECT). The authors review the literature and their clinical experience with such a drug combination at one psychiatric hospital. They conclude that the clinical and experimental findings to date are insufficient to warrant proscribing the combination of lithium and ECT on the basis of possible potentiation of neuromuscular blockade by lithium.     

The relationship between testosterone levels and cognitive ability patterns.

The cognitive performance of normal men and women was studied, grouped according to whether the subjects had relatively high or low salivary testosterone (T) concentrations. Men with lower T performed better than other groups on measures of spatial/mathematical ability, tasks at which men normally excel. Women with high T scored higher than low-T women on these same measures. T concentrations did not relate significantly to scores on tests that usually favor women or that do not typically show a sex difference. These results support suggestions of a nonlinear relationship between T concentrations and spatial ability, and demonstrate some task specificity in this respect.     

氯丙咪嗪血药浓度与疗效的相关研究

目的 :探讨氯丙咪嗪治疗抑郁症的口服剂量、血药浓度与临床疗效之间关系 ,及其有效血浓度范围。　方法 :符合 CCMD- 2诊断标准的抑郁症病人 30例 ,汉密尔顿抑郁量表 (HAMD)评分2 1～ 45分 ,平均 (34.87± 6 .5 3)分 ;纽卡斯尔抑郁诊断量表 (NDI)评分 6～ 10分进入研究。以不定剂量氯丙咪嗪口服治疗 ,共治疗 8周。以 HAMD减分率评定疗效。荧光免疫偏振分析仪 (TDx)测第14天稳态血药浓度。　结果 :氯丙咪嗪剂量 2 5～ 10 0 m g/ d时血浓度范围变异很大 [46～ 44 7ng/ ml,平均 (183± 86 ) ng/ m l];口服剂量与血药浓度呈非线性相关 (P<0 .0 5 ) ;血药浓度与临床疗效显著相关(r=- 0 .5 5 2 ,P=0 .0 0 16 ) ,呈指数曲线关系。　结论 :氯丙咪嗪有效血浓度在 12 6～ 40 0 ng/ ml之间 ,临床长期使用应以血药浓度监测手段指导     

The relationship between uric acid levels and Huntington's disease progression

Uric acid (UA) may be associated with the progression of Parkinson's disease and related neurodegenerative conditions; however, its association with Huntington's disease (HD) progression has not been explored. A secondary analysis of 347 subjects from the CARE‐HD clinical trial was performed to examine the relationship between baseline UA levels and the level of functional decline in HD. Outcomes included change in scores at 30 months for the Unified Huntington's Disease Rating Scale components. There was less worsening of total functional capacity over time with increasing baseline UA levels (adjusted mean worsening in scores: 3.17, 2.99, 2.95, 2.28, 2.21, from lowest to highest UA quintile, P = 0.03). These data suggest a possible association between higher UA levels and slower HD progression, particularly as measured by total functional capacity. If confirmed, UA could be an important predictor and potentially modifiable factor affecting the rate of HD progression. © 2009 Movement Disorder Society     

Tapping and peg insertion after levodopa intake in treated and de novo parkinsonian patients

BACKGROUND: Investigators use instrumental tasks for objective assessment of parkinsonian motor disability and its drug response. To date, such studies on treated parkinsonian patients have not addressed acute and long-term effects of dopaminergic drugs. OBJECTIVES: To determine the impact of long-term dopaminergic therapy within a standardized levodopa challenge test design in combination with two repeatedly performed instrumental tasks, peg insertion and tapping, in previously treated and untreated parkinsonian patients. RESULTS: Tapping significantly deteriorated in previously untreated, but not in treated parkinsonian patients after levodopa intake. In contrast, motor symptoms and peg insertion significantly improved in both groups of parkinsonian patients. Results of both tests differed between parkinsonian patients and matched controls. CONCLUSION: Worsening of cognitively less demanding tapping may result from upregulated presynaptic inhibitory feedback regulation, sedative effects of levodopa or dopamine overflow in untreated parkinsonian patients, who are sensitive to these effects in contrast to treated parkinsonian patients. Tapping is a task with autonomic repetitive performance and programming of standardised movements with a low need for cognitive effort. This autonomic functioning of attentional control and selective processing is intact in Parkinson's disease. Peg insertion depends on more complex movements and thus hypothetically on dopamine-associated cognitive processes. Therefore, impairment of peg insertion responded to dopaminergic stimulation in both groups of parkinsonian patients. Future studies on the efficacy of antiparkinsonian drugs, using instrumental tasks for objective assessment, should consider long-term impact of antiparkinsonian drug therapy and associated cognitive efforts.