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Welcome to Our Parkinson's Place


I copy news articles pertaining to research, news and information for Parkinson's disease, Dementia, the Brain, Depression and Parkinson's with Dystonia. I also post about Fundraising for Parkinson's disease and events. I try to be up-to-date as possible. I have Parkinson's
diseases as well and thought it would be nice to have a place where
updated news is in one place. That is why I began this blog.
I am not responsible for it's contents, I am just a copier of information searched on the computer. Please understand the copies are just that, copies and at times, I am unable to enlarge the wording or keep it uniformed as I wish. This is for you to read and to always keep an open mind.
Please discuss this with your doctor, should you have any questions, or concerns. Never do anything without talking to your doctor. I do not make any money from this website. I volunteer my time to help all of us to be informed. Please no advertisers. This is a free site for all.
Thank you.


Saturday, October 17, 2015

HOW TO USE PARKINSON’S LAW TO YOUR ADVANTAGE


POSTED BY:  | OCTOBER 16, 2015
Work expands to fill the time available for its completion. 
If you’re into productivity, you’ll know this proverb as Parkinson’s Law. This interesting statement was made by Cyril Northcote Parkinson, the famous British historian and author, in 1955 – first appearing as the opening line in an article for The Economist and later becoming the focus of one of Parkinson’s books, Parkinson’s Law: The Pursuit of Progress.
Parkinson was qualified to make such a statement, having worked in the British Civil Service, seeing first hand how bureaucracy ticks. Bureaucracy itself is a by-product of our culture, thanks to the limiting belief that working harder is somehow better than working smarter and faster.
Parkinson’s Law – work expands to fill the time available for its completion – means that if you give yourself a week to complete a two hour task, then (psychologically speaking) the task will increase in complexity and become more daunting so as to fill that week. It may not even fill the extra time with more work, but just stress and tension about having to get it done. By assigning the right amount of time to a task, we gain back more time and the task will reduce in complexity to its natural state.
I once read a response to Parkinson’s Law insinuating that if it were an accurate observation, one would be able to assign a time limit of one minute to a task and the task would become simple enough to complete within that minute. But Parkinson’s Law is exactly that – an observation, not some voodoo magic. It works because people give tasks longer than they really need, sometimes because they want some ‘leg room’ or buffer, but usually because they have an inflated idea of how long the task takes to complete. People don’t become fully aware of how quickly some tasks can be completed until they test this principle.
Most employees who defy the unwritten rule of “work harder, not smarter” know that, despite the greater return on investment for the company, it’s not always appreciated. That’s related to the idea that the longer something takes to complete, the better quality it must inherently be. Thankfully, the increasing trend of telecommuted employment is changing this for those lucky early adopters, but only because employers have no idea what you’re doing with all that spare time!
Let’s look at a few ways you can apply Parkinson’s Law to your life, get your to-do list checked off quicker and spend less of the work day filling in time just to look busy. This is relevant whether you work in an office or at home, since “work harder, not smarter” is a cultural idea that many individuals fall prey to even when nobody’s supervising their work.

Running Against the Clock

Make a list of your tasks, and divide them up by the amount of time it takes to complete them. Then give yourself half that time to complete each task. You have to see making the time limit as crucial. Treat it like any other deadline. Part of reversing what we’ve been indoctrinated with (work harder, not smarter) is to see the deadlines you set for yourself as unbreakable – just like the deadlines your boss or clients set.
Use that human, instinctual longing for competition that fuels such industries as sports and gaming to make this work for you. You have to win against the clock; strive to beat it as if it were your opponent, without taking shortcuts and producing low-quality output. This is particularly helpful if you’re having trouble taking your own deadlines seriously.
At first, this will be partially an exercise in determining how accurate your time projections for tasks are. Some may be spot on to begin with, and some may be inflated. Those that are spot on may be the ones that you are unable to beat the clock with when you halve the time allotment, so experiment with longer times. Don’t jump straight back to the original time allotment because there may be an optimum period in between.
If you work at a computer, a digital timer is going to be very useful when you start doing this. It’ll also save you a bit of time, because a timer allows you to see at a glance how much longer you have. Using your clock involves some addition and subtraction! There are free utilities available for OS XLinux, and Windows.

Crush the Cockroaches of the Productivity World

Look for those little time-fillers, like email and feed reading, that you might usually think take ten or twenty (or even, god forbid, thirty!) minutes. These are the “cockroaches” of the productivity world – little pests that do nothing but make your life a pain in the backside, pains that you can’t seem to get rid no matter how much you run around the house with a shoe or bug spray.
Instead of doing the leisurely 20-30 minute morning email check, give yourself five minutes. If you’re up for a challenge, go one better and give yourself two minutes. Don’t give these tasks any more attention until you’ve completed everything on your to-do list that day, at which point you can indulge in some email reading, social networking and feed reading to your heart’s content. Not that I recommend you spend all your spare time that way!
These are tasks where 10% of what you do is important and 90% is absolutely useless. This forces you to tend to the important tasks – feeds you need to read in order to improve in your work (for instance, if you’re a web designer who needs to be read up on new practices), and emails that are actually high-priority. Experiment with how far you can take this. Make your criteria for what makes an email important, really strict and the penalties harsh! That means using the Delete button, by the way – I’m not advocating violence against your colleagues.
and squashing your deadlines down to the bare minimum in many areas of your life. Just be conscious of the line between ‘bare minimum’ and ‘not enough time’ – what you’re aiming for is a job well done in less time, not a disaster that’s going to lose you employment or clients.

http://healthpassion.info/how-to-use-parkinsons-law-to-your-advantage/

3 Myths About Parkinson’s Disease


One of the highest-achieving athletes of the 20th century is boxing champion Muhammad Ali, but to Maryum Ali, he’s just dad.
As she has watched her father become one of the most famous faces of Parkinson’s disease since his diagnosis nearly 30 years ago, she has learned much about the realities of Parkinson’s, said Maryum. who is known to her family as May May.
Currently, about 1 million people in the U.S. have Parkinson’s, which results from a loss of the brain cells that produce the chemical dopamine. The condition causes tremors, rigid muscles and impaired balance.
In the early days of her father’s diagnosis, information about the condition was scarce. “Even doctors didn’t understand it,” she told MyHealthNewsDaily.
But still today, myths about Parkinson’s persist.
“People think that it’s a disease of older people,” she said. While it’s true that the majority of people with Parkinson’s develop the condition around the age of 60, it is increasingly being diagnosed in younger people, she said.
About 10 percent of people with Parkinson’s are diagnosed before age 40, according to the National Parkinson Foundation.Another myth, Ali said, is that there is not much that can be done to help a person with Parkinson’s. “There’s this, ‘it is what it is’ mindset out there,” she said.
People should know that there are effective ways to deal with the symptoms of Parkinson’s, she said. Exercise enormously helped her father, she said.
In fact, a study published this month in the journal Geriatrics and Gerontology International found that of Parkinson’s patients who participated in weekly, one-hour exercise sessions reported improvements in their daily activities compared with a control group who didn’t exercise.
Brain stimulation treatments also help, Ali said. It’s important to find a specialist who is familiar with all available options, she said. “You can do lots of different things; it’s not like there’s no hope.”
A third myth about the condition is that it’s highly genetic, Ali said. “Lots of people think this, but only 5 percent of people who get it have a genetic tie,” she said.
Scientists don’t know exactly what causes Parkinson’s disease. While genetics play a role, most researchers believe that chemicals in the environment increase a person’s risk of the condition, according to the National Institutes of Health.
Viruses and inflammation in the body have also been linked with the condition, the NIH says.
Pass it on: Parkinson’s disease can strike younger people, but for all patients, exercise and other treatment may help with symptoms.
http://healthcaresolutionsplus.org/3-myths-about-parkinsons-disease/

The Victory Summit® Parkinson's Event Will Energize, Inform and Change Lives

Davis Phinney Foundation's National Symposium Comes to San Antonio


SAN ANTONIOOct. 14, 2015
The Davis Phinney Foundation is bringing nationally and locally recognized movement disorder specialists to San Antonio to share research, treatments and practical tools for living well today with Parkinson's disease. The Victory Summit® symposium on November 14, 2015 is a free event, open to the public. Registration at www.davisphinneyfoundation.org/VSSanAntoniois strongly encouraged.
People living with Parkinson's, their care partners and family members can anticipate a unique, energizing event that will educate and motivate attendees to take action to create a better quality of life.
An attendee of a past event remarked, "I wasn't feeling great that morning, which made it harder to get there, but it was worth it. The Victory Summit changed my life. My hesitation subsided with the genuine camaraderie and support from others and knowledge of how to improve the way that I'm living with the disease."
"Come join us for an uplifting day filled with movement and informative speakers. You'll leave with a wealth of practical information for living well and connect with invaluable resources close to home," said founder, Olympic medalist and American cycling legend turned Parkinson's advocate, Davis Phinney.
The symposium runs from 10:00am to 3:45pm at the Hyatt Regency Hill Country. Details can be found on the website: www.davisphinneyfoundation.org/VSSanAntonio
Topics for the event include cognitive and non-motor symptoms; the importance of social capital; Dance for PD®; keynote address by Davis Phinney. Breakout sessions include Parkinson's 101, deep brain stimulation, care partner strategies, sleep disturbances, pain management, depression and medication management. 
Parkinson's Disease
Parkinson's disease is a progressive disorder of the nervous system that affects movement and causes non-motor symptoms. More than 1.5 million Americans live with it. Its incidence is higher in the over-60 age group, although diagnosis at younger ages is increasingly common. 

Davis Phinney Foundation
The Davis Phinney Foundation was created in 2004 to help people with Parkinson's disease live well today. Its major initiatives include: the Every Victory Counts® manual; The Victory Summit® symposia series; the Living Well Challenge™ educational webinar series; the "Parkinson's Exercise Essentials" video and the funding of research focused on quality of life therapies. 
Visit the website: www.davisphinneyfoundation.org.

Contact: Robin Andrews
910-617-2697
randrews@davisphinneyfoundation.org


http://health.einnews.com/article/291577445/8q1bmth9TbvDIHrA

Friday, October 16, 2015

Hepatitis C Virus Infection: A Risk Factor for Parkinson's Disease

October 16, 2015                            Very Important:


Hepatitis C Virus Infection: A Risk Factor for Parkinson's Disease

W. Y.-Y. Wu; K.-H. Kang; S. L.-S. Chen; S. Y.-H. Chiu; A. M.-F. Yen; J. C.-Y. Fann; C.-W. Su; H.-C. Liu; C.-Z. Lee; W.-M. Fu; H.-H. Chen; H.-H. Liou

Disclosures
J Viral Hepat. 2015;22(10):784-791. 

      Abstract

      Recent studies found that hepatitis C virus (HCV) may invade the central nervous system, and both HCV and Parkinson's disease (PD) have in common the overexpression of inflammatory biomarkers. We analysed data from a community-based integrated screening programme based on a total of 62 276 subjects. We used logistic regression models to investigate association between HCV infection and PD. The neurotoxicity of HCV was evaluated in the midbrain neuron–glia coculture system in rats. The cytokine/chemokine array was performed to measure the differences of amounts of cytokines released from midbrain in the presence and absence of HCV. The crude odds ratios (ORs) for having PD were 0.62 [95% confidence interval (CI), 0.48–0.81] and 1.91 (95% CI, 1.48–2.47) for hepatitis B virus (HBV) and HCV. After controlling for potential confounders, the association between HCV and PD remained statistically significant (adjusted OR = 1.39; 95% CI, 1.07–1.80), but not significantly different between HBV and PD. The HCV induced 60% dopaminergic neuron death in the midbrain neuron–glia coculture system in rats, similar to that of 1-methyl-4-phenylpyridinium (MPP+) but not caused by HBV. This link was further supported by the finding that HCV infection may release the inflammatory cytokines, which may play a role in the pathogenesis of PD. In conclusion, our study demonstrated a significantly positive epidemiological association between HCV infection and PD and corroborated the dopaminergic toxicity of HCV similar to that of MPP+.

      Introduction

      Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra, accompanied by the accumulation of α-synuclein aggregates in Lewy bodies.[1]Although the cause of PD remains unclear, it has been shown that numerous viruses are associated with both acute and chronic parkinsonism including influenza, Coxsackie, Japanese encephalitis (JE), western equine encephalitis, herpes and acquired immunodeficiency disorder (HIV). These viruses are neurotropic and they may induce a number of encephalopathies that lead to parkinsonism.[2] Hepatitis C virus (HCV) belongs to the flaviviridae family, which includes well-known neurotropic viruses, such as JE, yellow fever, dengue and tick-borne encephalitis viruses.[3] Recent studies suggest that HCV may invade the central nervous system (CNS). Such neuroinvasive harm shows sign of evidence that patients with mild chronic HCV infection had elevated choline/creatine ratios, a biomarker indicating inflammatory and infective conditions, in the basal ganglia and white matter.[4] Moreover, a viral replicative intermediate of HCV RNA has been found in autopsy brain tissue and activation of macrophages/microglial cells has been found in HCV-positive patients.[5,6] In addition, alteration of striatal dopaminergic neurotransmission has been reported in HCV-infected patients.[7] The evidence that HCV can replicate in the CNS suggests a possible link between PD and HCV.
      The association between HCV infection and the pathogenesis of PD is also supported by both HCV infection and PD having in common the overexpression of inflammatory biomarkers that are related to rising concentrations of cytokines in neuronal generation processes, such as abnormal protein handling, oxidative stress, mitochondrial dysfunction, excitotoxicity and apoptotic processes.[6]
      Despite this speculation, it is rare and difficult to have available information on HCV infection and PD simultaneously in a population- and community-based epidemiological study to assess this hypothesis. Thus, at population and epidemiology level, we attempted to assess whether HCV infection was associated with PD using data from the Keelung community-based integrated screening (KCIS) programme with information on HCV infection, diagnosis of PD and other confounding factors available.[8] At the molecular level, we investigated the dopaminergic toxicity of HCV and compared that of 1-methyl-4-phenylpyridinium (MPP+), the pathognomonic chemical in experimental parkinsonism study. Furthermore, the differences in the relative amounts of cytokines released from midbrain in the presence and absence of virus were measured by cytokine/chemokine array to investigate the pathogenesis of PD.
      Materials and Methods
      Study Population and Community-based Model for Ascertained PD
      The study population was derived from a community-based integrated screening programme in Keelung (KCIS), the northernmost area in Taiwan.[8] A total of 63 163 subjects aged 40 or older were enrolled between 2000 and 2004. The ascertainment of PD was either through active community-based survey or hospital-based clinical series cases. The medical record consisted of information on medical visits, such as ICD codes, date of visit and prescriptions. The three major diagnostic codes were kept for financial reimbursement for all treatments, therapies and prescriptions. The major diagnostic code 332.0 was used to identify patients with PD and excluded parkinsonism caused by other reasons, such as vascular disease-related parkinsonism, drug-induced parkinsonism, multiple system atrophy and parkinsonism secondary to brain insults. Finally, 887 PD cases were found.
      Serum Viral Markers and Biochemical Variables
      In the KCIS programme, HBsAg was detected using radioimmunoassay kits (Abbott Laboratories, Chicago, IL, USA), and anti-HCV was detected using a third-generation enzyme immunoassay (Abbott Laboratories). Venous blood samples were taken after the subjects had fasted at least 12 h for the measurement of plasma glucose, triacylglycerol, total cholesterol, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. The definition of metabolic syndrome was based on the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, that is when ≥3 of the following criteria were satisfied: (i) central obesity (waist circumference ≥90 cm for men and ≥80 cm for women), (ii) hypertriacylglycerolemia (≥150 mg/dL), (iii) an abnormally low HDL-cholesterol concentration (<40 mg/dL for men and <50 mg/dL for women), (iv) raised blood pressure (≥130 mmHg systolic or ≥85 mmHg diastolic) or (v) a raised fasting glucose concentration (≥100 mg/dL).
      Harvest of HCV or HBV Viral Particles From Serum
      To prepare the HCV or hepatitis B virus (HBV) viral particles, 1 mL of serum from the chronic hepatitis B or C patients, and 0.5 mL of 30% polyethylene glycol 6000 in 1.5 m NaCl was added and left overnight at 4 °C. The sample was then centrifuged for 30 min at 3300 g, and the pellet was resuspended in culture medium for the coculture experiments. The viral titre of the medium was quantified by real-time PCR using an ABI 5700 sequence detection system (PE Applied Biosystems, Warrington, UK).
      Midbrain Neuron–Glia Coculture
      Neuron–glia cocultures from E-14 Wistar embryonic rat midbrain were obtained. Midbrain neuro-glia coculture has been used to study neuroinflammation in vitro, such as the potential neuroprotective effect of anti-inflammatory compounds. For the details of the test refer to Hung's paper.[9] The cells were seeded in Dulbecco's Modified Eagle's Medium (DMEM) with 10% foetal bovine serum at 5 × 105 in 24-well plates previously coated with poly-D-lysine. The culture was kept in a humidified chamber at 37 °C in a 5% CO2 atmosphere. Twenty-four hours after plating, the culture was changed to Minimum Essential Medium (MEM) with 2% FBS and 2% horse serum. After 1 week, the primary midbrain neuron–glia cocultures were treated with 100 nm MPP+ in the presence or absence of testing compounds for 48 h. Dopaminergic neurons were characterized by immunostaining with a rabbit antityrosine hydroxylase (anti-TH) antibody (1:5000; Calbiochem, Darmstadt, Germany). A biotinylated goat anti-rabbit IgG was used for staining revealed by the ABC method (Vector Laboratories, Burlingame, CA, USA) and developed using 0.04% (w/v) diaminobenzidine to produce a brown reaction product. The number of TH (+) cell was counted under a microscope.
      Cytokine/Chemokine Arrays
      Commercially available cytokine antibody arrays from R&D Systems (Minneapolis, MN, USA, Proteome Profiler Rat Cytokine Array Panel A; ARY008) were used to measure differences in the relative amounts of cytokines released from midbrain in the presence and absence of virus. The array consists of a nitrocellulose membrane dotted with antibodies that recognize 29 distinct cytokines, chemokines and growth factors. Following a 48 h incubation of midbrain cultures with or without HBV or HCV, the culture media were collected for analysis. A detection antibody cocktail consisting of 29 biotinylated antibodies, each targeted to a specific cytokine, was added to the treated media samples. The media were then incubated overnight at 4 °C with the cytokine antibody arrays. Following this, the media was washed from the array and a Streptavidin–HRP solution was added to the membrane for 30 min at room temperature. The cytokine array was again washed, and a chemiluminescent HRP substrate (EMD Millipore, Darmstadt, Germany) was added to the membrane. The membranes were then exposed to X-ray film for 1–5 min, and the relative pixel density of each spot on the array was quantified using Image J (National Institutes of Health, Bethesda, MD, USA) software.
      Statistical Analysis
      The relationships between hepatitis virus infection status, demographic factors, smoking habits, metabolic syndrome and PD were expressed as odds ratios (OR) and 95% confidence intervals (CI) using a univariate logistic regression model. Interactions between all pairs of factors were tested in the model. Afterwards, the adjusted ORs of hepatitis virus, smoking and metabolic syndrome were estimated after controlling for age, gender, education level and also possible interactions between the two variables. To compute adjusted odds ratios for the association between HCV and PD, smoking and metabolic syndrome together with age, gender and education levels were retained in the final model.


      Results
      Table 1 shows the frequencies of different characteristics in the study population. Of 61 363 participants, subjects aged over 60 years accounted for 57%. In total, 7137 (11.71%) individuals were HBsAg(+) and 2729 (4.48%) were anti-HCV(+). The carrier rate of HBsAg in males was higher than in females (13.21% vs 10.73%), but the carrier rate of anti-HCV was lower in males than females (3.59% vs 5.06%). The prevalence of metabolic syndrome was 32.21% and 30.10% in males and females, respectively.
      The crude ORs for having PD were 1.11 (95% CI, 1.11–1.12) and 1.43 (95% CI, 1.25–1.64) for age and gender, respectively. The risk of PD was lower among high (more than 13 years of education) or intermediate education levels (10–12 years) (OR = 0.29; 95% CI, 0.23–0.37, and OR = 0.35; 95% CI, 0.26–0.47, respectively) as compared with those with low education level (<10 years). After testing for the interaction between each two independent variables of interest, only the interaction between gender and levels of education was statistically significant.
      In the univariate analysis, the crude ORs for having PD for HBV and HCV infection were 0.62 (95% CI, 0.48–0.81) and 1.91 (95% CI, 1.48–2.47) (Table 2). After controlling for age, gender, education level and the interaction between gender and education level, the association between HCV and PD still remained statistically significant (adjusted OR = 1.39; 95% CI, 1.07–1.80). However, the association between HBV infection and PD was not statistically significant in the multivariable regression analysis (adjusted OR = 1.01; 95% CI, 0.77–1.32). The interactions between gender and hepatitis virus infection were not significant. Furthermore, the positive association still remained between HCV and PD (adjusted OR = 1.40; 95% CI, 1.08–1.82) after adjusting for age, gender, education level, the interaction between gender and education level, smoking and metabolic syndrome.
      MPP+and HCV-induced Dopaminergic Neuronal Death in Neuron–Glia Cocultures
      MPP+ (100 nm) induced loss of TH (+) neurons by 29.5 ± 2.8% in midbrain neuron–glia cocultures (Fig. 1b). In the presence of HCV but not HBV, the toxic effect of MPP+ was significantly increased in a dose-dependent manner (Fig. 1g). The toxicity of MPP+ was increased up to 50% by co-incubation with 104 HCV viral particles/mL. Application of HCV (105 viral particles/mL) induced neurotoxicity in TH+ neurons directly by 26.1 ± 3.2% in midbrain neuron–glia cocultures (Fig. 1f) which was similar to that of MPP+ (100 nm) (P < 0.05), whereas HBV (105 viral particles/mL) did not cause neurotoxicity in TH (+) neurons in the midbrain neuron–glia cocultures (Fig. 1e).


      The toxicity in vitro of HBV, hepatitis C virus (HCV) and MPP+. Midbrain neuron–glia cocultures were obtained from E14 Wistar rats. (a) Midbrain cells of the control group. (b–d) The MPP+ (100 nm) induced loss of TH+ neurons in midbrain neuron–glia cocultures and that with MPP+ combined with HBV (105 viral particles/mL) or MPP+ combined with HCV (105 viral particles/mL). (e) Failure of HBV (105 viral particles/mL) to cause neurotoxicity of TH+ neurons. (f) HCV induced (105 viral particles/mL) loss of TH+ neurons similar to that of MPP+ (100 nm). (g) Quantitative analysis of survival of TH+ neurons in midbrain neuron–glia cocultures at 48 h. The MPP+ (100 nm) induced loss of TH+ neurons by 29.5 ± 2.8%, similar to that of HCV (26.1 ± 3.2%). *P < 0.05 compared with control. # P < 0.05 compared with HCV (103 viral particles/mL). Bar represents 150 μm.

      Figure 2 shows the released cytokines from midbrain with HCV or HBV infection or control. Of the 29 distinct cytokine, chemokines and growth factors detected by the array (Fig. 2a), the soluble intercellular adhesion molecule-1 (sICAM-1), LPS–induced CXC chemokine (LIX), regulated on activation normal, T cell expressed and secreted (RANTES) increased in the HCV- and HBV-infected samples (Fig. 2b). Moreover, the levels of cytokines in the HCV-infected samples were higher compared with those of HBV-infected samples (Fig. 2c). The most prominent increase was found in the level of LIX (eight fold). Interestingly, the down-regulation of the tissue inhibitors of metalloproteinases-1 (TIMP-1) was only obvious in the HCV-infected samples.


      The cytokine/chemokine results in the presence and absence of viruses. (a) The positions of cytokines on the membrane are shown in the array map provided by the manufacturer (Proteome Profiler Rat Cytokine Array Panel A; ARY008). (b) Medium collected from rat midbrain neuron–glia coculture exposed to Control, HBV or hepatitis C virus (HCV) (105 viruses/mL) for 48 h. The levels of several chemokines in medium from midbrain culture were affected by HBV or HCV including RANTES, TIMP-1, LIX and sICAM-1. (c) Bar graph illustrates the relative expression levels of cytokines/chemokines based on densitometry of signal intensities. *P < 0.05 compared with control. # P < 0.05 compared with HBV.

      Discussion

      Epidemiologically, we found that anti-HCV(+) patients had statistically significant increased risk of developing PD in the population-based study. This finding was further supported by HCV-induced dopaminergic neuronal toxicity in vitro. The dopaminergic neuronal toxicity induced by HCV was similar to that of MPP+. The levels of chemokines such as sICAM-1, LIX and RANTES were increased, and TIMP-1 was down-regulated in the HCV-infected midbrain culture.
      Hepatitis C virus is a positive-strand RNA virus of the flaviviridae family that primarily infects hepatocytes, causing acute and chronic liver disease, but it is also associated with a variety of CNS abnormalities, such as cognitive dysfunction, fatigue and depression.[10,11] Although the evidence for extrahepatic HCV replication is still controversial,[12] a recent study showed that the essential HCV receptors (including CD81, claudin-1, occluding, LDLR and scavenger receptor-B1) are expressed on brain microvascular endothelial cells, a major component of the blood–brain barrier (BBB), that may provide a gate for HCV to infect the CNS.[13] This is supported by the detection of negative-strand HCV RNA in postmortem brain tissue.[5]
      Hepatitis C virus-infected patients have been demonstrated to have impairment of midbrain dopaminergic function.[7] Our study found that HCV can induce dopaminergic neuronal toxicity similar to that of MPP+. Viruses may directly injure neurons by viral replication or through activation of both innate and adaptive immune responses resulting in neuronal damage through inflammation.[1] The emerging evidence has shown that inflammation makes a significant contribution to neuronal death in PD.[6] Levels of proinflammatory mediators, including TNF-α, IL-6 and IL-1β, are elevated in the brains and peripheral blood mononuclear cells of patients with PD.[14] HCV infection also stimulates macrophages or monocytes to release proinflammatory mediators.[15,16] In our study, we found that sICAM-1 and RANTES were significantly up-regulated by HCV in rat midbrain neuron–glia coculture. Serum levels of circulating ICAM-1 rise in inflammatory diseases of the CNS.[17] In autopsy brains of PD, the activated microglia with overexpression of ICAM-1 were up-regulated in the SN and putamen.[18] ICAM-1-positive reactive astrocytes in PD are indicative of a sustained inflammatory process.[19] Astrocytes can be induced to produce sICAM-1, which can induce a TNF-α-dependent inflammation and damage the dopaminergic neurons in PD.[20]
      RANTES signalling upstream of caspase activation plays a key role in neuronal apoptosis.[21] Human microglia synthesize RANTES in response to pro-inflammatory stimuli, and anti-inflammatory cytokines regulate the production of RANTES by activated microglia.[22,23] CD4+ T cells have a pivotal role in accelerating CNS inflammation and demyelination within infected mice, by regulating RANTES expression, which in turn coordinates the trafficking of macrophages into the CNS, leading to myelin destruction.[24] The overexpression of sICAM-1 and RANTES might result in neuroinflammation and facilitation of PD progression.
      It has been reported that LIX was up-regulated in primary astrocytes after exposing to neurotoxin.[25]More recently, using a cerebellar slice culture system, it has been reported that lysolecithin promoted the release of LIX, which results in demyelination.[26] We found that LIX was significantly up-regulated by HCV in the midbrain culture and may indicate the potential dopaminergic neuronal damage.
      In addition, we found that TIMP-1 was down-regulated by HCV. TIMP-1 is an important marker for neuroinflammatory and neurodegenerative diseases.[27] TIMP-1 is known to aid cell survival. The TIMP family inhibits the activity of matrix metalloproteinases (MMPs), a large family of zinc-dependent proteases.[28] TIMP-1 is currently studied with particular interest in CNS disease progression because of its robust overexpression in response to inflammatory myelin injury.[29] TIMP-1 is predominantly expressed in astrocytes and likely acts as an endogenous factor to rescue cells from the toxic effects of MMP activities during neuroinflammation.[30] Cerebrospinal fluid (CSF) and brain tissue samples from HIV-1-associated patients with dementia showed reduced TIMP-1 levels compared to control patients.[31]Furthermore, TIMP-1/MMP expression in neuroinflammation can impact neuronal function and survival in disease conditions. A recent study also shows the direct role of TIMP-1 in neuroprotection, indicating that its expression serves as a neuroprotective response of astrocytes.[32] Here, we found that TIMP-1 was down-regulated by HCV, suggesting that one of the neuroprotectants derived from astrocytes was inhibited by HCV infection.
      Chronic infection with HCV induces insulin resistance, leading to metabolic syndrome and the underlying pathway through the expression of cytokines, such as TNF-α and IL-6.[14] Thus, the influence of HCV infection on PD may be confounded by metabolic syndrome. However, after adjustment for metabolic syndrome, the positive association between HCV and PD still remained. This result also supported the fact that HCV can pass through the blood–brain barrier to induce neuroinflammation and lead to PD.
      We failed to find a significant association between HBV infection and PD in the community-based integrated screening programme. The lack of association between HBV infection and PD was also consistent with Forton et al.'s[4] findings that an elevated choline/creatine ratio was not seen in patients with HBV infection. In addition, our results revealed that HBV does not induce dopaminergic neuronal toxicity. Furthermore, there is no neuroinvasive evidence of HBV, neither of the Hepadnaviridae family in general, to which HBV belongs.
      The positive association between HCV infection and PD has clinical implications for high endemic HCV areas. The WHO has estimated that the prevalence of HCV infection is 2.2–3% worldwide, representing 130–170 million people.[33–35] Taiwan is an endemic area for hepatitis viruses and chronic liver disease.[36] The seroprevalence of anti-HCV in Taiwan reaches 4.4% in the general population.[37] As therapy for chronic hepatitis or liver disease has improved, older-onset diseases, such as PD, have been gradually noticed more often.[38] Because of the positive association between HCV and PD which is independent of metabolic syndrome, neurological tests may be considered in anti-HCV(+) groups to detect the earlier stages of PD.
      In summary, our study not only demonstrated a significantly positive association between HCV infection and PD from a large population-based epidemiological study but also proved the dopaminergic neuronal toxicity by HCV in vitro at the molecular level through an increase in cytokines induced by HCV.
      http://www.medscape.com/viewarticle/852066

      PDF-Funded Research Paves the Way to Phase III Drug Trial


      PDF Research Advocates Advising Trial into Nutritional Supplement Inosine

      The Parkinson’s Disease Foundation (PDF) is pleased to announce that research initially launched with PDF funding will be tested in a phase III clinical trial opening in 2016. The study, which two of PDF’s volunteer Research Advocates are helping to oversee, is assessing the potential of the nutritional supplement inosine for the treatment of Parkinson’s disease.
      Several studies, including early research funded by PDF in 2007 through its grant to the Parkinson Study Group, have shown that high levels of urate (a naturally occurring salt in the body) are associated with slower rate of progression in Parkinson’s disease. The PDF-funded retrospective study entitled, "Predicting PD Progression Subtypes by CSF Urate Pathways,” led by Michael Schwarzschild, M.D., Ph.D., of MassGeneral Institute of Neurodegenerative Disease, looked at urate levels in thousands of people with PD who had participated in clinical trials.
      This early research paved the way for Dr. Schwarzschild to study a nutritional supplement called inosine, which the body converts to urate, for its potential as a treatment for Parkinson’s disease. This research has now progressed to a phase III clinical trial called SURE-PD3 (Study of URate Elevation in Parkinson’s Disease) — the final stage of research before a new treatment can be approved by the US Food and Drug Administration (FDA) for use by the public.
      PDF is pleased that two of its Research Advocates have active roles on the clinical trial — representing the Parkinson’s community and ensuring that the patient perspective is central.
      Becky Houde, J.D. of Boston, MA: is a member of the SURE-PD3 steering committee, the group that oversees and supervises the trial.
      Joel Grace, Ph.D., of Big Flats, NY: is a member of the SURE-PD3 Data Safety and Monitoring Board, the group that monitors the safety of all trial participants.
      Enrollment for the double-blinded placebo-controlled trial will begin in 2016, and will seek 270 people living with early-stage Parkinson’s to investigate whether moderate urate elevation resulting from two years of inosine treatment slows PD progression. It will be conducted at 60 Parkinson Study Group sites across the US and is supported by the National Institute of Neurological Disorders and Stroke.
      For further information on this research or the role of patient advocates, contact the PDF HelpLine at info@pdf.org or (800) 457-6676. Enrollment is not yet open but information will be available next year. 
      https://www.blogger.com/blogger.g?blogID=4282591254614897626#editor/target=post;postID=8580902676956430748

      Thursday, October 15, 2015

      MOUSE MODEL EXPLAINS SIDE-EFFECTS OF DRUGS USED FOR PARKINSON’S DISEASE

      POSTED BY:  | OCTOBER 13, 2015




      The most effective treatment for Parkinson’s disease is the long-term use of a medication called L-DOPA or levodopa. Unfortunately, a common side effect of the drug is a movement problem called dyskinesia. Often, this side-effect is as debilitating as Parkinson’s disease itself.
      In a new study, researchers have now discovered why long-term use of L-DOPA (levodopa), leads to dyskinesia.
      Using a new method for manipulating neurons in a mouse model of Parkinson’s, a Columbia University Medical Center (CUMC) research team found that dyskinesia arises when particular nerve cells (striatonigral) become less responsive to GABA, an inhibitory neurotransmitter.
      Experts believe this finding suggests that it may be possible to modulate the activity of these neurons to prevent or delay this disabling side effect.
      A paper explaining the finding was published recently in the online edition of the journal Neuron.
      Parkinson’s disease is a progressive neurodegenerative disorder. Brain cells die in various parts of the brain, especially in a region called the substantia nigra.
      It is in the substantia nigra that a neurotransmitter called dopamine is formed — a substance that helps nerve cells work normally. When dopamine is insufficient or lacking, neurons fire abnormally, impairing one’s ability to control movement.
      “While Parkinson’s is not curable, it is treatable with L-DOPA, which is converted into dopamine in the brain,” said study leader David L. Sulzer, Ph.D.

      However, while taking L-DOPA helps patients move normally, in many individuals it eventually triggers uncontrolled excessive movements.” Parkinson’s is estimated to affect about one million people in the U.S. and up to 10 million worldwide.
      Most studies into the cause of dyskinesia in Parkinson’s have focused on the dopamine receptors that remain in the brain, which over time become over-reactive to L-DOPA therapy. However, the CUMC team decided to look at how neurons of the basal ganglia regulates movement in the absence of dopamine.
      “Dopamine neurons modulate the basal ganglia,” explained lead author Anders Borgkvist, Ph.D., a postdoctoral fellow in Dr. Sulzer’s laboratory. “And because that circuit is still running in patients with Parkinson’s, it’s long been suspected that other parts of the circuit behave abnormally in this disease.”
      However, scientists lacked a way to stimulate selective parts of the basal ganglia to evaluate what was happening when dopamine is no longer available. The CUMC team employed a novel form of optogenetics, a technique that uses light to control neurons that have been genetically sensitized to light, and found that after long-term dopamine loss, striatonigral neurons lose their ability to respond to the neurotransmitter GABA (gamma-aminobutyric acid). This effect was not found with short-term dopamine loss.
      “When striatonigral neurons are working normally, they act as a brake on the basal ganglia, in effect shutting down unwanted movement,” said Dr. Sulzer.
      “But when there is dopamine loss, as in Parkinson’s, striatonigral neurons try to compensate, and eventually lose their responsiveness to GABA. Our hypothesis is that when L-DOPA is added into the system, you lose the ability to filter, or turn off, unwanted movement.”
      “Our findings suggest that GABA and GABA receptors are still present in the striatonigral neurons,” said Dr. Borgkvist.
      “So then the question becomes, why they aren’t functional? I think that we, or another lab, will eventually find the answer. In any case, the implication is that this defect is correctable, and that would mean that we could prevent or at least delay dyskinesia, so that patients could continue to use L-DOPA.”
      “Patients do not develop dyskinesias in the early stages of Parkinson’s, but only after several years of the disease,” said Stanley Fahn, MD.A major reason why these patients want to delay the initiation of L-DOPA therapy is to avoid these dyskinesias for as long as possible. These new findings open up possible ways to treat or prevent the dyskinesias. If such treatments were found, patients would probably seek to be treated early and improve their quality of life sooner.”

      http://healthpassion.info/mouse-model-explains-side-effects-of-drugs-used-for-parkinsons-disease/