- A descriptive systematic review of salivary TDM in neonates and infants. [Journal Article]
- BJBr J Clin Pharmacol 2018 Feb 14
- CONCLUSIONS: There is significant potential for infantile saliva testing and in particular, for neutral and weakly acidic compounds. Of the properties investigated, pKa was the most influential with both logP and protein binding having little effect on this correlation. To conclude any compound with a pKa within physiological range (pH 6 - 8) should be considered with extra care, with the extraction and analysis method examined and optimized on a case-by-case basis.
- [Essential tremor: state of the art]. [Review]
- NNervenarzt 2018 Feb 05
- Essential tremor (ET) is currently classified as a syndrome rather than a unique disease, primarily involving monosymptomatic action tremor in both hands. Different etiologies are presumed to underli...
Essential tremor (ET) is currently classified as a syndrome rather than a unique disease, primarily involving monosymptomatic action tremor in both hands. Different etiologies are presumed to underlie this condition. Currently only a few monogenetic conditions are known to present with this syndrome. If accompanied by additional symptoms that do not in themselves constitute a new syndrome, such as abnormal tandem gait or postures, the syndrome should be diagnosed as "ET plus". ET is associated with abnormal rhythmic activation of the cerebello-thalamo-cortical tremor circuit. Despite its strong heritability, the genetics of ET have not been elucidated as yet. Age-correlated tremor is one of the presumed subgroups of ET. Late onset is associated with a shortened life expectancy. From a treatment perspective, propranolol and primidone represent the drugs of first choice, followed by topiramate. Deep brain stimulation of the Vim nucleus of the thalamus is a proven treatment option in severely affected patients.
- Patient Evaluation and Selection for Movement Disorders Surgery: The Changing Spectrum of Indications. [Journal Article]
- PNProg Neurol Surg 2018; 33:80-93
- This report summarizes the state-of-the-art and controversies around patient selection for deep brain stimulation (DBS) for various conditions. Parkinson's disease (PD): several class I studies have ...
This report summarizes the state-of-the-art and controversies around patient selection for deep brain stimulation (DBS) for various conditions. Parkinson's disease (PD): several class I studies have shown superiority of DBS over best medical treatment for advanced PD with fluctuations and further inclusion criteria. One class I study suggests that PD patients with early motor complications might gain more quality of life if operated within 3 years after the onset of fluctuations. The subthalamic nucleus (STN) is still the standard target. STN DBS has an impact on impulse control disorders though the exact mechanism is unclear. Tremor: essential tremor (ET) patients found to be eligible for DBS surgery should first be treated with primidone, propranolol, and with a combined therapy preoperatively. Second-line drugs (i.e., topiramate and gabapentin) may be useful. No class I studies exist for DBS treatment of ET. The optimal target of DBS in ET might be the posterior subthalamic area. Dystonia: there is class I evidence for primary generalized and segmental dystonia and for some botulinum-resistant focal dystonias. The impact of age, symptom duration, and DYT-mutation status in primary dystonia on the outcome of DBS surgery clearly demands more studies. DBS has a role in SCGE-mutation positive myoclonus dystonia and tardive dystonia. Finally, neurostimulation in secondary dystonia might be considered in selected patients based on an individual patient's approach.
- Brain circuits and neurochemical systems in essential tremor: insights into current and future pharmacotherapeutic approaches. [Journal Article]
- ERExpert Rev Neurother 2018; 18(2):101-110
- There are few medications that are available for the treatment of essential tremor (ET) and they are only moderately effective. Areas covered: Data were obtained from a PubMed search. Original articl...
There are few medications that are available for the treatment of essential tremor (ET) and they are only moderately effective. Areas covered: Data were obtained from a PubMed search. Original articles, review articles, and clinical guidelines were included. Two disease models for ET have been proposed: 1) the olivary model, which attributes ET to a pathological pacemaker in the inferior olivary nucleus, and 2) the cerebellar degeneration model, which postulates that ET originates in the cerebellum and could be related to deficient or abnormal Purkinje cell (PC) output. Underlying biochemical dysfunction in T-type calcium channels (T-tCaC) may loosely be linked to the first model and deficiency/abnormality in γ-aminobutyric acid (GABA) neurotransmission, to the second. Expert commentary: Human data points robustly to the role of GABA in ET. Numerous medications that target the GABA system have been tried, with variable success. Given the many different types of GABA-ergic neurons, and the multitude of GABAAreceptor subtypes, a given medication could have competing/cancelling effects. It would seem that influencing GABA receptors broadly is not as effective as targeting certain GABAAreceptor subtypes. Future research should seek to identify molecular candidates that have a more targeted effect within the GABA system.
- Warfarin resistance from primidone in patient with essential tremor. [Letter]
- EJEur J Clin Pharmacol 2018; 74(3):377-378
- Monitoring enzymatic degradation of emerging contaminants using a chip-based robotic nano-ESI-MS tool. [Journal Article]
- ABAnal Bioanal Chem 2018; 410(1):27-32
- Up to now, knowledge of enzymes capable of degrading various contaminants of emerging concern (CEC) is limited, which is especially due to the lack of rapid screening methods. Thus, a miniaturized hi...
Up to now, knowledge of enzymes capable of degrading various contaminants of emerging concern (CEC) is limited, which is especially due to the lack of rapid screening methods. Thus, a miniaturized high-throughput setup using a chip-based robotic nanoelectrospray ionization system coupled to mass spectrometry has been developed to rapidly screen enzymatic reactions with environmentally relevant CECs. Three laccases, two tyrosinases, and two peroxidases were studied for their ability to transform ten pharmaceuticals and benzotriazole. Acetaminophen was most susceptible to enzymatic conversion by horseradish peroxidase (HRP), laccase from Trametes versicolor (LccTV), and a tyrosinase from Agaricus bisporus (TyrAB). Diclofenac and mefenamic acid were converted by HRP and LccTV, whereas sotalol was solely amenable to HRP conversion. Benzotriazole, carbamazepine, gabapentin, metoprolol, primidone, sulfamethoxazole, and venlafaxine remained persistent in this study. The results obtained here emphasize that enzymes are highly selective catalysts and more effort is required in the use of fast monitoring technologies to find suitable enzyme systems. Despite the methodological limitations discussed in detail, the automated tool provides a routine on-line screening of various enzymatic reactions to identify potential enzymes that degrade CECs. Graphical abstract A chip-based robotic nano-ESI-MS tool to rapidly monitor enzymatic degradation of environmentally relevant emerging contaminants.
- Botulinum Toxin in Management of Limb Tremor. [Review]
- TToxins (Basel) 2017 Nov 10; 9(11)
- Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the distal or proximal upper extrem...
Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the distal or proximal upper extremity. Quality of life is often affected and one's ability to perform daily tasks becomes impaired. Oral therapies, including propranolol and primidone, can be effective in the management of essential tremor, although adverse effects can limit their use and about 50% of individuals lack response to oral pharmacotherapy. Locally administered botulinum toxin injection has become increasingly useful in the management of essential tremor. Targeting of select muscles with botulinum toxin is an area of active research, and muscle selection has important implications for toxin dosing and functional outcomes. The use of anatomical landmarks with palpation, EMG guidance, electrical stimulation, and ultrasound has been studied as a technique for muscle localization in toxin injection. Earlier studies implemented a standard protocol for the injection of (predominantly) wrist flexors and extensors using palpation and EMG guidance. Targeting of muscles by selection of specific activators of tremor (tailored to each patient) using kinematic analysis might allow for improvement in efficacy, including functional outcomes. It is this individualized muscle selection and toxin dosing (requiring injection within various sites of a single muscle) that has allowed for success in the management of tremors.
- Essential tremor. [Journal Article]
- CMAJCMAJ 2017 11 06; 189(44):E1364
- Biocatalytic degradation of pharmaceuticals, personal care products, industrial chemicals, steroid hormones and pesticides in a membrane distillation-enzymatic bioreactor. [Journal Article]
- BTBioresour Technol 2018; 247:528-536
- Laccase-catalyzed degradation of a broad spectrum of trace organic contaminants (TrOCs) by a membrane distillation (MD)-enzymatic membrane bioreactor (EMBR) was investigated. The MD component effecti...
Laccase-catalyzed degradation of a broad spectrum of trace organic contaminants (TrOCs) by a membrane distillation (MD)-enzymatic membrane bioreactor (EMBR) was investigated. The MD component effectively retained TrOCs (94-99%) in the EMBR, facilitating their continuous biocatalytic degradation. Notably, the extent of TrOC degradation was strongly influenced by their molecular properties. A significant degradation (above 90%) of TrOCs containing strong electron donating functional groups (e.g., hydroxyl and amine groups) was achieved, while a moderate removal was observed for TrOCs containing electron withdrawing functional groups (e.g., amide and halogen groups). Separate addition of two redox-mediators, namely syringaldehyde and violuric acid, further improved TrOC degradation by laccase. However, a mixture of both showed a reduced performance for a few pharmaceuticals such as primidone, carbamazepine and ibuprofen. Mediator addition increased the toxicity of the media in the enzymatic bioreactor, but the membrane permeate (i.e., final effluent) was non-toxic, suggesting an added advantage of coupling MD with EMBR.
New Search Next
- Is essential tremor a single entity? [Review]
- EJEur J Neurol 2018; 25(1):71-82
- Essential tremor (ET) is a frequent movement disorder. The new tremor classification has subdivided ET into the classical form with bilateral action tremor of the hands with or without involvement of...
Essential tremor (ET) is a frequent movement disorder. The new tremor classification has subdivided ET into the classical form with bilateral action tremor of the hands with or without involvement of further tremor locations and without any other explaining signs or symptoms for the tremor and into 'ET plus' which comes additionally with further neurological signs of unknown origin. This will provide a better foundation for subclassifying the condition. The immediate cause of ET is a preformed oscillating network within the central nervous system as revealed with electrophysiological methods. The reason why this network is getting into the tremor mode is unclear. Pathology has so far not convincingly proved neurodegeneration for the condition but possibly adaptive changes of the brain particularly in the cerebellum are likely. Genetics have not yet provided insight into the molecular causes of the condition but several genetic diseases presenting with an ET syndrome have been uncovered. Treatment options cover medication (propranolol, primidone, topiramate) and surgical interventions with deep brain stimulation, gamma-knife surgery and the recently introduced magnetic resonance imaging guided focused ultrasound lesioning. Further progress is awaited from the better integration of large prospective cohort assessment and basic science studies on the possible etiologies. In particular, aging-related tremor may explain a large number of the patients seen in clinical practice. Currently ET is considered a clinically relatively uniform condition with presumably various underlying etiologies.