Toksiline parkinsonism psühhostimulanti süstivatel noortel narkomaanidel

Ülevaates on kirjeldatud toksilist parkinsonistlikku sündroomi patsientidel, kes süstivad Sudafedist (pseudoefedriinist) valmistatud lahust, mis lisaks psühhostimulant efedroonile (metkatinoon) sisaldab kõrvalproduktina suures hulgas mangaani. Peamisteks sümptomiteks on tasakaalu-, kõnnaku- ja kõnehäired, jäsemete düstooniad ning bradükineesia. Toksilise ekstrapüramidaalse sündroomi kliiniline pilt sarnaneb manganismiga, mida on varem kirjeldatud mangaani kroonilise inhalatsiooni tagajärjel tööstustöölistel. Efedrooni sisaldava isevalmistatud segu tarvitamine on oluline parkinsonistliku sündroomi tekkepõhjus noortel narkomaanidel. Eesti Arst 2013; 92(6):320–32

Manganese-Induced Parkinsonism due to Ephedrone Abuse

During recent years, a syndrome of hypokinesia, dysarthria, dystonia, and postural impairment, related to intravenous use of a “designer” psychostimulant derived from pseudoephedrine using potassium permanganate as the oxidant, has been observed in drug addicts in several countries in Eastern Europe with some cases also in Western countries. A levodopa unresponsive Parkinsonian syndrome occurs within a few months of abusing the homemade drug mixture containing ephedrone (methcathinone) and manganese. The development of this neurological syndrome has been attributed to toxic effects of manganese, but the role of the psychostimulant ephedrone is unclear. This paper describes the clinical syndrome, results of neuroimaging, and therapeutic attempts

Peripheral Blood RNA Expression Profiling in Illicit Methcathinone Users Reveals Effect on Immune System

Methcathinone (ephedrone) is relatively easily accessible for abuse. Its users develop an extrapyramidal syndrome and it is not known if this is caused by methcathinone itself, by side-ingredients (manganese), or both. In the present study we aimed to clarify molecular mechanisms underlying this condition. We used microarrays to analyze whole-genome gene expression patterns of peripheral blood from 20 methcathinone users and 20 matched controls. Gene expression profile data were analyzed by Bayesian modeling and functional annotation. Of 28,869 genes on the microarrays, 326 showed statistically significant differential expression with FDR adjusted p-values below 0.05. Quantitative real-time PCR confirmed differential expression for the most of the genes selected for validation. Functional annotation and network analysis indicated activation of a gene network that included immunological disease, cellular movement, and cardiovascular disease functions (enrichment score 42). As HIV and HCV infections were confounding factors, we performed additional stratification of subjects. A similar functional activation of the “immunological disease” category was evident when we compared subjects according to injection status (past versus current users, balanced for HIV and HCV infection). However, this difference was not large therefore the major effect was related to the HIV status of the subjects. Mn–methcathinone abusers have blood RNA expression patterns that mostly reflect their HIV and HCV infections

Development of new levodopa treatment strategies in Parkinson’s disease—from bedside to bench to bedside

<p>This review will illustrate the process of moving from an idea through preclinical research and Galenic developments into clinical investigations and finally to approval by regulatory agencies within the European Union. The two new treatment strategies described, levodopa/carbidopa intestinal gel and levodopa/carbidopa microtablets, for advanced Parkinson’s disease, have been developed in collaborative research within departments at Uppsala University. With this historical approach, reference priority is given to reports considered to be of special importance for this more than two decades long process ‘from bedside to bench to bedside’.</p

Focused proteomics in post-mortem human spinal cord.

With a highly sensitive electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS) system, proteins were identified in minimal amounts of spinal cord from patients with the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and compared to proteins in spinal cord from control subjects. The results show 18 versus 16 significantly identified (

Levodopa/carbidopa microtablets in Parkinson disease : pharmacokinetics and blinded motor assessment

The aim of this study was to characterize the levodopa and carbidopa plasma concentration in relation to blinded motor function ratings. This is a part of a study where a Multimodal motor Symptoms Quantification (MuSyQ) platform consisting of three different types of sensors were tested while evoking motor fluctuations with levodopa/carbidopa(LD/CD) microtablets in fluctuating Parkinson’s disease (PD) patients. Today, dose titration and chronic treatment largely relies on the patient’s subjective assessment of symptoms and clinicians’ assessment of patient status during a visit at the clinic. This was a single-center, open-label, single dose study in patients experiencing motor fluctuations. Patients were given 150% of their individual levodopa equivalent morning dose. Blood sampling and motor function testing were conducted for up to 6.5 hours at prespecified time points. The patients performed standardized motor activities for clinical rating in accordance with parts of the Unified Parkinson’s disease Rating Scale (UPDRS) and Unified Dyskinesia RatingScale (UDysRS). Each test cycle was video recorded, and the video sequences were presented to three movement disorder specialists in a randomized order for blinded rating of UPDRS items and the treatment response scale (TRS). Concentration versus time profiles and the pharmacokinetics were compared with a study previously conducted in healthy subjects. Nineteen patients, 14 male and 5 female, were included in the study. The individual LD/CD doses ranged between 110/27.5mg to 410/102.5 mg. The concentration time profiles are similar to the LD/CD microtablet profiles reported in healthy subjects. The blinded video ratings managed to capture the most distinctive movements. This is the first pharmacokinetic study where patients received LD/CD microtablets. For patients fluctuating from 'off' to dyskinetic, the relationship between the plasma concentration and motor function was clearer compared to the patients that fluctuated to a lesser extent

Levodopa/carbidopa microtablets in Parkinson disease : pharmacokinetics and blinded motor assessment

The aim of this study was to characterize the levodopa and carbidopa plasma concentration in relation to blinded motor function ratings. This is a part of a study where a Multimodal motor Symptoms Quantification (MuSyQ) platform consisting of three different types of sensors were tested while evoking motor fluctuations with levodopa/carbidopa(LD/CD) microtablets in fluctuating Parkinson’s disease (PD) patients. Today, dose titration and chronic treatment largely relies on the patient’s subjective assessment of symptoms and clinicians’ assessment of patient status during a visit at the clinic. This was a single-center, open-label, single dose study in patients experiencing motor fluctuations. Patients were given 150% of their individual levodopa equivalent morning dose. Blood sampling and motor function testing were conducted for up to 6.5 hours at prespecified time points. The patients performed standardized motor activities for clinical rating in accordance with parts of the Unified Parkinson’s disease Rating Scale (UPDRS) and Unified Dyskinesia RatingScale (UDysRS). Each test cycle was video recorded, and the video sequences were presented to three movement disorder specialists in a randomized order for blinded rating of UPDRS items and the treatment response scale (TRS). Concentration versus time profiles and the pharmacokinetics were compared with a study previously conducted in healthy subjects. Nineteen patients, 14 male and 5 female, were included in the study. The individual LD/CD doses ranged between 110/27.5mg to 410/102.5 mg. The concentration time profiles are similar to the LD/CD microtablet profiles reported in healthy subjects. The blinded video ratings managed to capture the most distinctive movements. This is the first pharmacokinetic study where patients received LD/CD microtablets. For patients fluctuating from 'off' to dyskinetic, the relationship between the plasma concentration and motor function was clearer compared to the patients that fluctuated to a lesser extent