Cieľom štúdie bolo poukázať na prínos nových invazívnych terapeutických postupov v liečbe pokročilých štádií Parkinsonovej choroby (PCh) v porovnaní s klasickou perorálnou farmakoterapiou. Výsledky boli získané zo súboru 43 pacientov s PCh, z ktorých 39 % podstúpilo klasickú terapiu pozostávajúcu z perorálnych antiparkinsoník, 23 % pacientov užívalo intestinálny gél obsahujúci levodopou (Duodopa), 19 % pacientov malo indikovanú apomorfínovú subkutánnu pumpu a 19 % pacientov podstúpilo hĺbkovú mozgovú stimuláciu (DBS). Väčšina pacientov mala pokročilejšie štádiá PCh, štádium 4 podľa Hoehnovej a Yahra (1967). Výsledky práce ukazujú zlepšenie stavu po nasadení nového terapeutického postupu u väčšiny pacientov v porovnaní s klasickou terapiou. Pozitívny vplyv bol zaznamenaný aj v zníženej potrebe užívania liekov per os, kde bol zaznamenaný signifikantný pokles pri všetkých nových terapeutických postupoch. Taktiež bol zaznamenaný pozitívny účinok v redukcii off stavov u pacientov. V prípade Duodopy a DBS došlo k skráteniu off periódy o 50 % a pri apomorfínovej pumpe o 40 %. Pacienti tiež hlásili zlepšenie niektorých symptómov ochorenia ako tremor či rigidita, zatiaľ čo dyskinézy naďalej predstavujú výzvu. Na základe získaných výsledkov sa môže konštatovať, že nové terapeutické postupy pri PCh umožnia zvládnuť symptómy typické pre pokročilé štádia ochorenia, ktoré by bez týchto postupov viedli k invalidite, čo je hlavným dôvodom ich indikácie. U pacientov s pomalšou progresiou ochorenia v skorých štádiách je klasická forma terapie perorálnymi antiparkinsonikami stále zlatým štandardom. Dôvodom je nielen ich relatívna účinnosť, ale aj lepšia ekonomická dostupnosť, nakoľko nové postupy sú spojené s vysokými finančnými nákladmi a v rámci verejného zdravotného poistenia môžu byť v Slovenskej republike použité len na základe rozhodnutia revízneho lekára.
The aim of the study was to point out the contribution of new invasive therapeutic procedures in the treatment of advanced stages of Parkinson’s disease (PD) in comparison with classical oral pharmacotherapy. Data originated from a group of 43 patients with PD, 39% (17) with classic treatment, 23% (10) with intestinal gel of methyl ester levodopa (Duodopa), 19% (8) of patients were using subcutaneous delivery of apomorphine (APO) and the same quantity of patients had undergone deep brain stimulation (DBS). Majority of patients had advanced stages of PD, stage 4, by standards of Hoehn and Yahr scale (Hoehn and Yahr, 1967). Research observed improvement in majority of patients with novel treatments. A positive effect was also noted in the reduced need for oral therapy, where there was a significant decrease in all new therapies. Benefits were observed in the amount of antiparkinsonic drugs taken per os, where we observed reduction in all new therapies. A positive effect of the new therapeutic approaches in reducing “off” periods in patients has also been noted. In the case of Duodopa and DBS, the ”off” period was shortened up to 50% and in the apomorphine pump up to 40%. Patients also reported reduction of some symptoms like rigidity, tremor and bradykinesis while dyskinesis still remains suba challenge. On the basis of the obtained results, it can be concluded that new therapeutic procedures for PCh will make it possible to manage symptoms typical of advanced stages of the disease, which without these procedures would lead to disability, which is the main reason for their indication. However, in early stages, well responding patients or in slow progressing disease oral antiparkinsonics are remaining as golden standard of treatment. This is not just due to good response but also because these classic drug formulations are significantly less expensive. In Slovakia, novel treatments are accessible through healthcare insurance only after secondary revision by insurance company doctors.
- Klíčová slova
- Duodopa, apomorfínová pumpa,
- MeSH
- apomorfin aplikace a dávkování terapeutické užití MeSH
- fixní kombinace léků MeSH
- hluboká mozková stimulace metody MeSH
- implantabilní infuzní pumpy MeSH
- karbidopa farmakologie terapeutické užití MeSH
- klinická studie jako téma MeSH
- levodopa farmakologie terapeutické užití MeSH
- lidé MeSH
- Parkinsonova nemoc * terapie MeSH
- Check Tag
- lidé MeSH
In the rat model, 6-hydroxydopamine (6-OHDA) known as a selective catecholaminergic neurotoxin used chiefly in modeling Parkinson's disease (PD). Continuous aerobic exercise and curcumin supplementations could play a vital role in neuroprotection. This study aimed to explore the neuroprotective roles of regular aerobic exercise and curcumin during PD. For this, rats were treated as follows for 8 consecutive weeks (5 d in a week): For this, animals were orally treated with curcumin (50 ml/kg) alone or in combination with aerobic exercise. Compared with a control group, induction of PD by 6-OHDA increased the amount of alpha-synuclein protein and malondialdehyde levels and decreased the number of substantia nigra neurons, total antioxidant capacity, and glutathione peroxidase activity in brain tissue. All these changes were abolished by the administration of curcumin with aerobic exercise treatments. Activity behavioral tests also confirmed the above-mentioned results by increasing the rod test time and the number of rotations due to apomorphine injection. Histopathology assays mimic the antioxidant activity and behavioral observations. Combined curcumin with aerobic exercise treatments is potentially an effective strategy for modifying the dopaminergic neuron dysfunction in 6-OHDA-induced rats modeling PD via dual inhibiting oxidative stress indices and regulating behavioral tasks.
- MeSH
- alfa-synuklein metabolismus MeSH
- antioxidancia metabolismus farmakologie MeSH
- apomorfin metabolismus farmakologie MeSH
- glutathionperoxidasa metabolismus MeSH
- krysa rodu rattus MeSH
- kurkumin * metabolismus farmakologie MeSH
- malondialdehyd MeSH
- modely nemocí na zvířatech MeSH
- neuroprotektivní látky * farmakologie MeSH
- neurotoxické syndromy * MeSH
- neurotoxiny metabolismus farmakologie MeSH
- oxidopamin toxicita MeSH
- Parkinsonova nemoc * farmakoterapie metabolismus MeSH
- substantia nigra MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND PURPOSE: This update of the treatment guidelines was commissioned by the European Academy of Neurology and the European section of the Movement Disorder Society. Although these treatments are initiated usually in specialized centers, the general neurologist and general practitioners taking care of PD patients should know the therapies and their place in the treatment pathway. METHODS: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the spectrum of approved interventions including deep brain stimulation (DBS) or brain lesioning with different techniques (radiofrequency thermocoagulation, radiosurgery, magnetic resonance imaging-guided focused ultrasound surgery [MRgFUS] of the following targets: subthalamic nucleus [STN], ventrolateral thalamus, and pallidum internum [GPi]). Continuous delivery of medication subcutaneously (apomorphine pump) or through percutaneous ileostomy (intrajejunal levodopa/carbidopa pump [LCIG]) was also included. Changes in motor features, health-related quality of life (QoL), adverse effects, and further outcome parameters were evaluated. Recommendations were based on high-class evidence and graded in three gradations. If only lower class evidence was available but the topic was felt to be of high importance, clinical consensus of the guideline task force was gathered. RESULTS: Two research questions have been answered with eight recommendations and five clinical consensus statements. Invasive therapies are reserved for specific patient groups and clinical situations mostly in the advanced stage of Parkinson's disease (PD). Interventions may be considered only for special patient profiles, which are mentioned in the text. Therapy effects are reported as change compared with current medical treatment. STN-DBS is the best-studied intervention for advanced PD with fluctuations not satisfactorily controlled with oral medications; it improves motor symptoms and QoL, and treatment should be offered to eligible patients. GPi-DBS can also be offered. For early PD with early fluctuations, STN-DBS is likely to improve motor symptoms, and QoL and can be offered. DBS should not be offered to people with early PD without fluctuations. LCIG and an apomorphine pump can be considered for advanced PD with fluctuations not sufficiently managed with oral treatments. Unilateral MRgFUS of the STN can be considered for distinctly unilateral PD within registries. Clinical consensus was reached for the following statements: Radiosurgery with gamma radiation cannot be recommended, unilateral radiofrequency thermocoagulation of the pallidum for advanced PD with treatment-resistant fluctuations and unilateral radiofrequency thermocoagulation of the thalamus for resistant tremor can be recommended if other options are not available, unilateral MRgFUS of the thalamus for medication-resistant tremor of PD can be considered only within registries, and unilateral MRgFUS of the pallidum is not recommended. CONCLUSIONS: Evidence for invasive therapies in PD is heterogeneous. Only some of these therapies have a strong scientific basis. They differ in their profile of effects and have been tested only for specific patient groups.
- MeSH
- apomorfin terapeutické užití MeSH
- hluboká mozková stimulace * metody MeSH
- kvalita života MeSH
- lidé MeSH
- neurologie * MeSH
- Parkinsonova nemoc * farmakoterapie MeSH
- tremor MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND PURPOSE: This update of the treatment guidelines was commissioned by the European Academy of Neurology and the European section of the Movement Disorder Society. Although these treatments are initiated usually in specialized centers, the general neurologist should know the therapies and their place in the treatment pathway. METHODS: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the spectrum of approved interventions including deep brain stimulation (DBS) or brain lesioning with different techniques (radiofrequency thermocoagulation, radiosurgery, magnetic resonance imaging-guided focused ultrasound surgery [MRgFUS] of the following targets: subthalamic nucleus [STN], ventrolateral thalamus, and pallidum internum [GPi]). Continuous delivery of medication subcutaneously (apomorphine pump) or through percutaneous ileostomy (intrajejunal levodopa/carbidopa pump [LCIG]) was also included. Changes in motor features, health-related quality of life (QoL), adverse effects, and further outcome parameters were evaluated. Recommendations were based on high-class evidence and graded in three gradations. If only lower class evidence was available but the topic was felt to be of high importance, clinical consensus of the guideline task force was gathered. RESULTS: Two research questions have been answered with eight recommendations and five clinical consensus statements. Invasive therapies are reserved for specific patient groups and clinical situations mostly in the advanced stage of Parkinson's disease (PD). Interventions may be considered only for special patient profiles, which are mentioned in the text. Therapy effects are reported as change compared with current medical treatment. STN-DBS is the best-studied intervention for advanced PD with fluctuations not satisfactorily controlled with oral medications; it improves motor symptoms and QoL, and treatment should be offered to eligible patients. GPi-DBS can also be offered. For early PD with early fluctuations, STN-DBS is likely to improve motor symptoms, and QoL and can be offered. DBS should not be offered to people with early PD without fluctuations. LCIG and an apomorphine pump can be considered for advanced PD with fluctuations not sufficiently managed with oral treatments. Unilateral MRgFUS of the STN can be considered for distinctly unilateral PD within registries. Clinical consensus was reached for the following statements: Radiosurgery with gamma radiation cannot be recommended, unilateral radiofrequency thermocoagulation of the pallidum for advanced PD with treatment-resistant fluctuations and unilateral radiofrequency thermocoagulation of the thalamus for resistant tremor can be recommended if other options are not available, unilateral MRgFUS of the thalamus for medication-resistant tremor of PD can be considered only within registries, and unilateral MRgFUS of the pallidum is not recommended. CONCLUSIONS: Evidence for invasive therapies in PD is heterogeneous. Only some of these therapies have a strong scientific basis. They differ in their profile of effects and have been tested only for specific patient groups. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Farmakoterapie extrapyramidových onemocnění zažívala svůj boom v průběhu devadesátých let minulého století, spíše v jeho druhé polovině, kdy většina klinických hodnocení v neurologických indikacích zkoumala efekt různých molekul na Parkinsonovu nemoc (PN) a další extrapyramidová onemocnění. Další dekáda byla v této oblasti ve znamení pozvolného útlumu velkých klinických hodnocení a na významu nabývalo zavádění nákladných forem léčby pokročilého stadia Parkinsonovy nemoci, spolu s rozšiřováním indikací léčby botulotoxinem (BoNT). Následná globální ekonomická krize zde v podstatě ukončila aktivity farmaceutického průmyslu a korporátní výzkum se soustředil na jiná odvětví medicíny či na jiné oblasti neurologie. Prakticky až posledních 5-7 let lze pozorovat jisté oživení farmakologického výzkumu, akademického i korporátního, na poli extrapyramidových onemocnění. Jsou zkoumány nové lékové formy L-DOPA, jsou zkoušeny nové molekuly ovlivňující u Parkinsonovy nemoci jiné systémy než dopaminergní; pozornost je věnována i non-motorické symptomatice nemoci, probíhá i intenzivní translační výzkum. Jsou zkoušeny nadějné molekuly v terapii neurodegenerativního atypického parkinsonismu. Léčba extrapyramidových dyskinezí (či "hyperkinezí") se spíše pozvolna zbavuje starších, "folklórních" stereotypů a standardizuje postupy na bázi "evidence-based medicine" (EBM). Velký rozvoj zaznamenávají nové postupy v léčbě dyskinezí botulotoxinem, ať už se jedná o distribuci lokální terapie, inovaci dávkovacích schémat nebo cílenou implikaci centrálního efektu léčby. Jakkoliv nelze oblast extrapyramidových onemocnění nazvat jedním z nejdynamičtěji se rozvíjejících odvětví neurologické terapie, je situace mnohem méně stacionární, než byla před deseti lety.
The pharmacotherapy for extrapyramidal diseases experienced a boom during the 1990s, particularly in the second half of the decade, when most clinical trials in neurological indications investigated the effect of various molecules on Parkinson's disease and other extrapyramidal diseases. The following decade witnessed a slow decline in large clinical trials, and an issue of growing importance was the introduction of costly forms of treatment of advanced-stage Parkinson's disease as well as expansion of indications for the treatment with botulinum toxin. The subsequent global economic crisis essentially ended the activities of the pharmaceutical industry in this area, and corporate research focused on other branches of medicine or on other fields of neurology. Only in the last five to seven years, there has been some revival of pharmacological research, both academic and corporate, into the field of extrapyramidal diseases. Novel L-DOPA dosage forms are being investigated and new molecules targeting other than dopaminergic systems in Parkinson's disease are being tested; attention is being paid to non-motor symptomatology of the disease and intensive translational research is underway. Promising molecules are being tested in the treatment of neurodegenerative atypical parkinsonism. The treatment of extrapyramidal dyskinesias (or hyperkinesias) rather slowly abandons old, traditional stereotypes and standardizes evidence-based medicine strategies. There is a major development in novel strategies in treating dyskinesia with botulinum toxin, whether it be distribution of local therapy, innovation in dosing schedules, or targeted implication of central treatment effect. Even though the field of extrapyramidal diseases is not one of the most dynamically developing areas of neurological treatment, the situation is much less stationary than it was ten years ago.
- MeSH
- antiparkinsonika terapeutické užití MeSH
- apomorfin terapeutické užití MeSH
- botulotoxiny terapeutické užití MeSH
- chorea farmakoterapie MeSH
- dystonie farmakoterapie MeSH
- gely terapeutické užití MeSH
- hluboká mozková stimulace MeSH
- léčivé přípravky MeSH
- levodopa terapeutické užití MeSH
- lidé MeSH
- myoklonus farmakoterapie MeSH
- nemoci bazálních ganglií * diagnóza farmakoterapie MeSH
- neurodegenerativní nemoci farmakoterapie MeSH
- parkinsonské poruchy diagnóza farmakoterapie MeSH
- tiky farmakoterapie MeSH
- tremor farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- porucha kontroly impulzů, dopamin-dysregulační syndrmom,
- MeSH
- agonisté dopaminu aplikace a dávkování MeSH
- antiparkinsonika aplikace a dávkování klasifikace MeSH
- antipsychotika aplikace a dávkování klasifikace MeSH
- apomorfin aplikace a dávkování MeSH
- delirium etiologie terapie MeSH
- diferenciální diagnóza MeSH
- hluboká mozková stimulace MeSH
- kombinovaná farmakoterapie metody MeSH
- kontraindikace MeSH
- levodopa aplikace a dávkování MeSH
- lidé MeSH
- Parkinsonova nemoc * diagnóza farmakoterapie genetika komplikace patofyziologie rehabilitace terapie MeSH
- riziko MeSH
- stupeň závažnosti nemoci MeSH
- úzkost etiologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- agonisté dopaminu aplikace a dávkování farmakologie MeSH
- apomorfin aplikace a dávkování farmakologie MeSH
- hodnocení výsledků zdravotní péče MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- Parkinsonova nemoc komplikace farmakoterapie MeSH
- senioři MeSH
- spinální svalová atrofie farmakoterapie etiologie MeSH
- subkutánní infuze MeSH
- zakřivení páteře farmakoterapie etiologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
- MeSH
- agonisté dopaminu MeSH
- apomorfin škodlivé účinky terapeutické užití MeSH
- infuzní pumpy MeSH
- lidé MeSH
- Parkinsonova nemoc * farmakoterapie komplikace patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are two enzymes sensitive to various chemical compounds having ability to bind to crucial parts of these enzymes. Boldine is a natural alkaloid and it was mentioned in some older works that it can inhibit some kinds of AChE. We reinvestigated this effect on AChE and also on BChE using acetyl (butyryl) thiocholine and Ellman's reagents as standard substances for spectrophotometric assay. We found out IC50 of AChE equal to 372 μmol/l and a similar level to BChE, 321 μmol/l. We conclude our experiment by a finding that boldine is cholinesterase inhibitor; however we report significantly weaker inhibition than that suggested in literature. Likewise, we tried to investigate the mechanism of inhibition and completed it with in silico study. Potential toxic effect on cholinesterases in real conditions is also discussed.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- aporfiny chemie farmakologie MeSH
- butyrylcholinesterasa chemie metabolismus MeSH
- cholinesterasové inhibitory chemie farmakologie MeSH
- HEK293 buňky MeSH
- lidé MeSH
- molekulární modely MeSH
- sekundární metabolismus * MeSH
- substrátová specifita účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Pokročilé štádiá Parkinsonovej choroby sú sprevádzané širokou škálou motorických i nemotorických komplikácií, ktoré závažnou mierou negatívne vplývajú na kvalitu života pacientov. Terapeutické ovplyvnenie týchto komplikácii, ktoré nielen vyplývajú z neurodegeneratívnej povahy základného ochorenia, ale sú podmienené i dlhodobým užívaním dopaminergnej liečby, predstavuje v klinickej praxi závažný problém. Liečebná stratégia sa v poslednom období upriamuje na zabezpečenie kontinuálnej dopaminergnej stimulácie, cieľom ktorej je dosiahnuť vyrovnanú kontrolu symptómov. S progresiou ochorenia a liekmi indukovaných komplikácií konvenčné farmakologické postupy často v tomto smere zlyhávajú. Do popredia terapeutického záujmu sa dostávajú iné, alternatívne spôsoby liečby, ktoré zohrávajú dôležitú úlohu pri liečbe prejavov Parkinsonovej choroby u pacientov v pokročilých štádiách ochorenia. Medzi tieto postupy patrí hĺbková mozgová stimulácia, subkutánne kontinuálne podávanie apomorfínu a liečba intestinálnym gélom levodopa/carbidopa. Správna selekcia pacientov, zohľadnenie prítomnosti špecifických nemotorických symptómov a potenciálnych rizík sprevádzajúcich jednotlivé liečebné modality sa významnou mieru podieľa na výbere najvhodnejšieho postupu.
Advanced stages of Parkinson‘s disease are accompanied by a broad scale of motor and non-motor complications which negatively impact patients' quality of life. The therapeutic influence of these complications resulting from the neurodegenerative nature of the underlying disease and are additionally caused by long-term use of dopaminergic treatment, represents a serious clinical problem. Recently, the therapeutic strategy has been focused on continuous dopaminergic stimulation to achieve the balanced control of symptoms. With disease progression and drug-induced complications conventional pharmacological procedures often fail to control clinical symptoms. Alternative methods rise to the forefront of therapeutic interest as they play an important role in the treatment of advanced Parkinson‘s disease. These options include: deep brain stimulation, subcutaneous application of apomorphine and levodopa/carbidopa intestinal gel therapy. Correct patient selection, consideration of specific non-motor symptoms and potential risks accompanying individual treatment modalities, significantly contribute to the selection of most appropriate procedure.
- MeSH
- apomorfin farmakologie terapeutické užití MeSH
- hluboká mozková stimulace metody využití MeSH
- karbidopa farmakologie terapeutické užití MeSH
- levodopa farmakologie terapeutické užití MeSH
- lidé MeSH
- motorické poruchy MeSH
- parenterální infuze metody MeSH
- Parkinsonova nemoc * komplikace terapie MeSH
- podkožní absorpce MeSH
- Check Tag
- lidé MeSH
