Neural substrates and potential treatments for levodopa-induced dyskinesias in Parkinson's disease

Parkinson’s disease (PD) is primarily a motor disorder that involves the gradual loss of motor function. Symptoms are observed initially in the extremities, such as hands and arms, while advanced stages of the disease can effect blinking, swallowing, speaking, and breathing. PD is a neurodegenerative disease, with dopaminergic neuronal loss occurring in the substantia nigra pars compacta, thus disrupting basal ganglia functions. This leads to downstream effects on other neurotransmitter systems such as glutamate, γ-aminobutyric acid, and serotonin. To date, one of the main treatments for PD is levodopa. While it is generally very effective, prolonged treatments lead to levodopa-induced dyskinesia (LID). LID encompasses a family of symptoms ranging from uncontrolled repetitive movements to sustained muscle contractions. In many cases, the symptoms of LID can cause more grief than PD itself. The purpose of this review is to discuss the possible clinical features, cognitive correlates, neural substrates, as well as potential psychopharmacological and surgical (including nondopaminergic and deep brain stimulation) treatments of LID

Motor symptoms in Parkinson's disease: A unified framework

Parkinson’s disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (akinesia and bradykinesia, tremor and rigidity), PD patients show additional motor deficits, including: gait disturbance, impaired handwriting, grip force and speech deficits, among others. Some of these motor symptoms (e.g., deficits of gait, speech, and handwriting) have similar clinical profiles, neural substrates, and respond similarly to dopaminergic medication and deep brain stimulation (DBS). Here, we provide an extensive review of the clinical characteristics and neural substrates of each of these motor symptoms, to highlight precisely how PD and its medical and surgical treatments impact motor symptoms. In conclusion, we offer a unified framework for understanding the range of motor symptoms in PD. We argue that various motor symptoms in PD reflect dysfunction of neural structures responsible for action selection, motor sequencing, and coordination and execution of movement

E-commerce adoption by SMEs in developing countries: evidence from Indonesia

This study aims to provide an overview of e-commerce adoption by SMEs in developing countries and, in particular, the extent of the adoption of e-commerce by Indonesian SMEs. It identifies the e-commerce benefits realized by these SMEs and investigates the relationship between the levels of e-commerce adoption and the benefits thus realized. The study was motivated by the limited studies related to e-commerce adoption by SMEs, especially in developing countries. In addition, it seems that most e-commerce studies are focused more on upstream issues: to see the factors that facilitate, or barriers faced regarding e-commerce adoption, rather than downstream issues: to see post-adoption benefits. This certainly limits our understanding about e-commerce adoption by SMEs in developing countries, as well as the post-adoption benefits of e-commerce. Indonesia was chosen as the place in which to conduct the study. A survey of 292 SMEs shows that the majority of them are still at an early stage in their adoption of e-commerce. Their use of e-commerce is dominated by marketing and purchasing and procurement activities. “Extending market reach”, “increased sales”, “improved external communication”, “improved company image”, “improved speed of processing”, and “increased employee productivity” are reported as the top six e-commerce benefits perceived by these SMEs. This study also shows that SMEs at the higher level of e-commerce adoption experience greater e-commerce benefits than those at other levels of adoption

Motivational modulation of bradykinesia in Parkinson's disease off and on dopaminergic medication.

Motivational influence on bradykinesia in Parkinson's disease may be observed in situations of emotional and physical stress, a phenomenon known as paradoxical kinesis. However, little is known about motivational modulation of movement speed beyond these extreme circumstances. In particular, it is not known if motivational factors affect movement speed by improving movement preparation/initiation or execution (or both) and how this effect relates to the patients' medication state. In the present study, we tested if provision of motivational incentive through monetary reward would speed-up movement initiation and/or execution in Parkinson's disease patients and if this effect depended on dopaminergic medication. We studied the effect of monetary incentive on simple reaction time in 11 Parkinson's disease patients both "off" and "on" dopaminergic medication and in 11 healthy participants. The simple reaction time task was performed across unrewarded and rewarded blocks. The initiation time and movement time were quantified separately. Anticipation errors and long responses were also recorded. The prospect of reward improved initiation times in Parkinson's disease patients both "off" and "on" dopaminergic medication, to a similar extent as in healthy participants. However, for "off" medication, this improvement was associated with increased frequency of anticipation errors, which were eliminated by dopamine replacement. Dopamine replacement had an additional, albeit small effect, on reward-related improvement of movement execution. Motivational strategies are helpful in overcoming bradykinesia in Parkinson's disease. Motivational factors may have a greater effect on bradykinesia when patients are "on" medication, as dopamine appears to be required for overcoming speed-accuracy trade-off and for improvement of movement execution. Thus, medication status should be an important consideration in movement rehabilitation programmes for patients with Parkinson's disease

A Practical Guide to Rodent Islet Isolation and Assessment

Pancreatic islets of Langerhans secrete hormones that are vital to the regulation of blood glucose and are, therefore, a key focus of diabetes research. Purifying viable and functional islets from the pancreas for study is an intricate process. This review highlights the key elements involved with mouse and rat islet isolation, including choices of collagenase, the collagenase digestion process, purification of islets using a density gradient, and islet culture conditions. In addition, this paper reviews commonly used techniques for assessing islet viability and function, including visual assessment, fluorescent markers of cell death, glucose-stimulated insulin secretion, and intracellular calcium measurements. A detailed protocol is also included that describes a common method for rodent islet isolation that our laboratory uses to obtain viable and functional mouse islets for in vitro study of islet function, beta-cell physiology, and in vivo rodent islet transplantation. The purpose of this review is to serve as a resource and foundation for successfully procuring and purifying high-quality islets for research purposes

Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. © 2010 Macmillan Publishers Limited. All rights reserved

Enhanced Fe2+ oxidation by mixed culture originated from hot spring: Application of response surface method

For maximum oxidation efficiency and minimum amount of jarosite, a total of 30 experimental runs were conducted and the experimental data fitted to the experimental quadratic model. The analysis of variance (ANOVA) demonstrated that the model was highly significant. Three dimensional plots were illustrated to depict the interaction between all the factors. The experimental results indicated that, the optimal conditions for the desired objects were 1.3, 7 g/l, 141 rpm and 35°C for the media initial pH, Fe2+ ion concentration, agitation rate and temperature, respectively. Using the regression model, a maximal oxidation efficiency of 55% and minimum jarosite precipitation of 0.34 g/l were achieved with the consideration of the optimal condition for the parameters at the end of 26 days of operation. The experiment was carried out under optimal condition and resulted in efficient oxidation and jarosite amount of 52% and 0.32 g/l, respectively. Similar values were predicted by the model. According to these results, the response surface methodology was not only applied to determine the significance information on the interaction between the factors, but also was conducted at optimal conditions for the desired objectives. It was also concluded that, the mixed culture isolated from the hot spring had the potential to oxidize ferrous to ferric irons.Key words: Biooxidation, response surface method, jarosite,  biodesulfurization, process optimization