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How patients with dementia show improvement with music therapy
Sunday, September 05, 2010
It’s been said that, “Music is a universal language”, and recent research with Dementia patients is proving that to be true; music can actually calm many patients and help to improve their memory! Dementia causes many changes in the brain that can, in a sense, short-circuit the brain. Alzheimer’s and Dementia patients may begin to get lost in familiar surroundings, repeat questions, become fearful of their surroundings, suspicious of family members that they may not recognize. They may have trouble following directions and doing the simplest daily tasks. They can become disoriented about time, places and people around them. Simply bathing, brushing their teeth, using a fork or spoon or even swallowing are typically forgotten and patients will end up being fed, strictly with liquids through tubes. Eventually, daily care can require up to six or more caregivers per patient, which is why so many end up in nursing facilities, but life doesn’t have to be all misery for them. With studies conducted in Belgium, Canada and the US, the findings are amazingly hopeful. We human beings seem to remember things that have emotional components. The parts of the brain, the Amygdala and our neurotransmitters, work together to help us recall the more emotional times that occur throughout our lives.
Petr Janata, a University of California, Associate Professor of Psychology, conducted brain activity experiments on a group of people who listened to music and found that the medial prefrontal cortex area of the brain stays healthier in Alzheimer’s patients longer than the other brain parts and has the capacity for emotions and other sensations. According to, Concetta Tomaino, at the Institute for Music and Neurologic Function, at the Beth Abraham Health Services, in New York; we can recall audio very easily and the audio functions are often one of the last abilities that we lose. This seems to allow Alzheimer’s and Dementia patients to still have the capacity to sing songs of their youth, despite losing the capacity to recall many words, phrases and names. Documented research has shown that it can even extend to the more advanced cases of the disease. Patients will often sing, hum and some even will begin to dance, despite the fact that minutes before they weren’t even speaking. Revisiting the music of earlier years can actually get these patients up and enjoying their day while even allowing them to have their memories stimulated; some patients recall the words to the songs even when they can’t recall their own family members’ names and faces. They were able to recall words and lyrics to many songs when hearing an audio recording than when they heard the lyrics spoken. The music therapy often consists of CD’s being played, appropriate to the age range of the individuals or groups. Usually, the music that they either enjoyed as children, teens or young adults; sometimes, a discussion of many of the individual pieces and their association with movies or other shows can stimulate memories associated with better times or time spent with loved ones. You can find CD’s, DVD’s and more at the local library that contain music familiar to the patients for whom you are caring. Familiar musicals, operas or Broadway show tunes can spark and open those mental trunks of long sealed away memories, giving many patients a memory boost and pleasure during their days. Classical music has been proven, time and time again, to be soothing, so if you can play music for about an hour during the daytime or evening for those you care for, it will help to keep them calm and relaxed. Studies have shown that more than an hour can sometimes create agitation or irritability. Playing an instrument, having a family sing-a-long can, as well and it allows some quality time with the family and friends that these patients wouldn’t otherwise be able to really enjoy. These and other amazing studies are allowing many patients to stay calm, less agitated; it reduces anxiety and decreases wandering, may allow patients to improve some memory functions while enjoying their sing-a-long time reminiscing about the music that they grew up with. It can increase their socialization and decrease some depression which is of immense help to caregivers. Perhaps someday, music will help researchers to unlock the secrets to aiding these patients and their caregivers in having a more fulfilling life despite their disease. by M. L. Kiser.
Dangers of Using Cheap or Counterfeit Medicines for PD
Friday, August 20, 2010
Dr. Chris
Parkinson's Disease Guide - Parkinson’s disease medicines can be expensive and the financial impact can be devastating in the long term, especially if health insurance is an issue. It is not uncommon for any chronic disease sufferer to seek alternate sources, especially if the more expensive branded medicine may be available at a cheaper rate.
However, the possibility should be kept in mind that the drug obtained from such sources is cheaper because it is a counterfeit or fake. This could mean that it may not have all the necessary ingredients, the proportions may be wrong, or it may contain harmful substances. In spite of taking the drugs as prescribed by the doctor, the patient may have slow or no improvement at all or may even deteriorate drastically.
Counterfeit and Cheap Parkinson’s Medicines
•Buying drugs from foreign sources may be cheaper but you can never be sure about the quality or efficacy of such drugs. Local government regulations may be significantly different from your country of origin and counterfeit drugs are not monitored for quality control.
•Cheaper drugs may actually be counterfeit, fake, or adulterated drugs, where useless or toxic substances could be substituted for the actual ingredients. Rather speak to your doctor about generics if you cannot afford your current drug regimen.
•Parkinson’s disease patients are heavily dependent upon their medicines to control their symptoms. Even a slight amount of dose alteration can produce severe fluctuations in their symptoms. With counterfeit medicines, you can never be sure about the exact composition of the drug, which can play havoc with the patient’s system. Either too little or too much of the active ingredient can be equally harmful.
•With tampering of the drug, unknown substances may be present in the drug, the effects of which can be dangerous. This can cause drug interactions with your regular PD medicines or other medication.
•There may be no improvement in a patient’s symptoms where previously there was good control of symptoms. Side effects and even an overdose is a possibility.
•New complications may arise which were not present earlier.
•Foreign drugs may contain substances which have not been approved as being safe or effective within your country of residence.
•It is illegal to bring in such drugs into the country and in case of any problem arising from the use of such drugs you will not have recourse to any corrective action.
•In the event that these drugs contain illicit substances, you may be convicted for the possession of narcotic substances.
Buying Cheap or Counterfeit PD Drugs
You may inadvertently acquire counterfeit drugs by :
•Ordering drugs from an online agency/pharmacy (over the internet).
•Buying drugs while holidaying overseas.
•Acquiring drugs from the local “black market”.
•Genuine but stolen drugs which are altered and then sold back into the distribution system.
•Genuine but expired drugs which are sold after re-packaging and changing the expiry date.
•Genuine drugs acquired from patients have got them free and sold them for a minimum price.
•Pharmacies may unknowingly keep counterfeit drugs supplied by dishonest wholesalers.
How to Avoid Using Counterfeit Drugs
While it may seem obvious, many consumers buy fake drugs unknowingly. These are some of the measures to ensure that you are only using genuine PD drugs as prescribed by your doctor.
•Avoiding buying medicines from doubtful online agencies.
•Buy medicines from reputable pharmacies.
•Be alert while buying medicines, taking care to look at the packaging and expiry dates.
•Being aware about the shape, color, size or other characteristics of medicines which are taken regularly.
•Avoiding buying medicines from foreign sources. Carry extra medicines while holidaying abroad and in the event that you need to acquire more medication, visit a reputable pharmacy in the area.
UC Parkinson's treatment shows promise
Tuesday, August 10, 2010
BY PEGGY O'FARRELL
Every morning, from about 8:30 to 10, Dan Truesdale froze up.
His muscles grew rigid, locked in place because of Parkinson's disease,until the medication finally kicked in, allowing to him get up, move around, live his life.
That changed last year when Truesdale, 47,became the first patient in Ohio to receive an experimental drug delivery system that gives his body a continual dose of the medication that lets him control his muscle movements.
His "frozen" muscles have thawed, Truesdale said.
"It's the best thing that's happened to me since I discovered I had Parkinson's," he said.
Researchers at the University of Cincinnati's Neuroscience Institute at University Hospital are recruiting more patients like Truesdale to test the system as part of a national phase 3 clinical trial.
Phase 3 trials are large-scale tests of new drugs or devices and the final step before federal health regulators decide to allow manufacturers to put new therapies on the market. Earlier phases test safety and effectiveness of new therapies on smaller scales.
Parkinson's disease is a chronic brain disorder in which brain cells that make the chemical dopamine die off. It usually strikes people over 50, and men are about50 percent more likely to get it than women.
Without dopamine,adults lose control of muscle movements and balance. Symptoms get worse over time, said Alberto Espay, the neurologist heading up UC's arm of the trial, and Parkinson's patients may eventually lose the ability to speak, feed themselves, swallow or chew.
Replacing the lost dopamine helps patients regain muscle control, but standard treatmentsgive dopamine in oral medications taken in several doses throughout the day.
That means the brain gets the dopamine it needs in interrupted allotments, so patients have periods throughout the day where they either can't move at all or they can't stop their bodies from moving involuntarily.
The drug delivery system Espay is testing aims to change that.
Abbott Pharmaceuticals' Levodopa-Carbidopa Intestinal Gel treatment system feeds the medication levodopa, which in the body becomes dopamine, into the upper intestine via a small tube surgically placed directly into the duodenum, or the very tip of the small intestine. The drug is fed through the tube from a cassette worn on the patient's body. A programmable pump lets the patient or doctor adjust the rate at which the medication is delivered.
"With this system, we're basically bathing the patient in dopamine at all times," Espay said.
Truesdale of Maineville used to be able to set his watch by his symptoms. The pump has changed all that. "I don't notice the passing of the hours because my symptoms have been reduced so drastically," he said.
He was diagnosed with Parkinson's in 2000, and has been on disability for the last four years. He recently began studying to become a minister.
The pump system is designed for patients like Truesdale with severe symptoms that are no longer controlled by standard medications, Espay said.
"People who've withdrawn from social and intellectual activities, they can resume them. We've seen people take up new activities after they've gone on the pump," he said.
Parkinson's Disease Placebo Response Increases with Expectations
Wednesday, August 04, 2010
Individuals with Parkinson's disease were more likely to have a neurochemical response to a placebo medication if they were told they had higher odds of receiving an active drug.
Chicago, IL - infoZine - "The promise of symptom improvement that is elicited by a placebo is a powerful modulator of brain neurochemistry," the authors write as background information to a report in the August issue of Archives of General Psychiatry, one of the JAMA/Archives journals. "Understanding the factors that modify the strength of the placebo effect is of major clinical as well as fundamental scientific significance." In patients with Parkinson's disease, the expectation of symptom improvement is associated with the release of the neurotransmitter dopamine, and the manipulation of this expectation has been shown to affect the motor performance of patients with the condition.
Sarah C. Lidstone, Ph.D., of Pacific Parkinson's Research Centre at Vancouver Coastal Health and the University of British Columbia, Vancouver, Canada, and colleagues studied 35 patients with mild to moderate Parkinson's disease undergoing treatment with the medication levodopa. On the first day of the study, a baseline positron emission tomographic (PET) scan was performed, participants were given levodopa and a second scan was performed one hour later to assess dopamine response. On the second day, patients were randomly assigned to one of four groups, during which they were told they had either a 25-percent, 50-percent, 75-percent or 100-percent chance of receiving active medication before the third scan; however, all patients were given placebo.
Patients who were told they had a 75-percent chance of receiving active medication demonstrated a significant release of dopamine in response to the placebo, whereas those in the other groups did not.
Patients' reactions to the active medication before the first scan was also correlated with their response to placebo. "Importantly, whereas prior medication experience (i.e., the dopaminergic response to levodopa) was the major determinant of dopamine release in the dorsal striatum, expectation of clinical improvement (i.e., the probability determined by group allocation) was additionally required to drive dopamine release in the ventral striatum," the authors write. Both areas have been shown to be involved with reward processing; in patients with a chronic debilitating illness who have responded to therapy in the past, expectation of therapeutic benefit in response to placebo has been likened to the expectation of receiving a reward.
"Our findings may have important implications for the design of clinical trials, as we have shown that both the probability of receiving active treatment—which varies in clinical trials depending on the study design and the information provided to the patient—as well as the treatment history of the patient influence dopamine system activity and consequently clinical outcome," the authors conclude. "While our finding of a biochemical placebo response restricted to a 75 percent likelihood of receiving active treatment may not generalize to diseases other than Parkinson's disease, it is extremely likely that both probability and prior experience have similarly profound effects in those conditions."
This study was funded by the Michael Smith Foundation for Health Research, the Canadian Institutes for Health Research and a TRIUMF Life Sciences Grant. Dr. Stoessl is supported by the Canada Research Chairs Program.
UCSF Gene Therapy Method Allays Parkinson’s Symptoms
Saturday, July 24, 2010
by Lauren HammitA novel technique created at UCSF to deliver a growth factor directly to brain cells has shown promising results in treating Parkinson’s symptoms and could enter human clinical trials as early as next year. The technique is part of an experimental treatment called gene therapy, which is considered a hopeful medical advance for neurodegenerative diseases such as Parkinson’s. Gene therapy involves introducing genetic material into a cell to cause the expression of a particular protein that can replace a missing or defective protein responsible for disease. The UCSF team demonstrated for the first time that the infusion system they designed successfully spread a targeted protein to critical regions in the primate brain. This resulted, on average, in a 50 percent improvement of symptoms that continued out to two years. “The approach is among the first shown to be beneficial to animals after they have already developed signs of Parkinson’s,” said Krystof Bankiewicz, MD, PhD, Kinetics Foundation Chair in Translational Research and professor of Neurological Surgery at UCSF. “Our ultimate goal is to reverse this disease in patients, and we hope this method will enable doctors to do exactly that.” Findings are published online and in the July 14, 2010, issue of the Journal of Neuroscience. In addition to an improvement in Parkinson’s symptoms, the treated animals also maintained a higher density of neurons that produce the brain chemical dopamine – the same neurons that disappear in Parkinson’s disease. Live imaging of the brain by positron emission tomography (PET) scanning, which has been used to gauge treatment effects in clinical studies of Parkinson’s, showed that those neurons remained active. “The scans enabled us to see where the protein went – and just as hoped, it had been taken up by neurons and transported along nerve fibers to where it was needed, the substantia nigra.” Bankiewicz said. Parkinson’s disease attacks thesubstantia nigra, which is a part of the brain that controls movement. A clinical trial is planned to test the safety of the method, according to the National Institutes of Neurological Disorders and Stroke, which funded this research. In a workup for the trial, the National Institutes of Health Rapid Access to Interventional Development (NIH RAID) program is supporting additional toxicity studies, as well as the production of clinical grade virus.
Top Ten Things to Know About Stem Cell Treatments
Saturday, July 10, 2010
There are different types of stem cellseach with their own purpose. |
| There are many different types of stem cells that come from different places in the body or are formed at different times in our lives. These include embryonic stem cells that exist only at the earliest stages of development and various types of tissue-specific or adult stem cells that appear during fetal development and remain in our bodies throughout life.
Our bodies use different types of tissue-specific stem cells to fit a particular purpose. Tissue-specific stem cells are limited in their potential and largely make the cell types found in the tissue from
which they are derived. For example, the blood-forming stem cells (or hematopoietic stem cells) in the bone marrow regenerate the blood, while neural stem cells in the brain make brain cells. A neural stem cell wont spontaneously make a blood cell and likewise a hematopoietic stem cell wont spontaneously make a brain cell. Thus, it is unlikely that a single cell type could be used to treat a multitude of unrelated diseases that involve different tissues or organs. Be wary of clinics that offer treatments with stem cells that originate from a part of the body that is different from the part being treated. |
2. A single stem cell treatment will not work on a multitude of unrelated diseases or conditions. |
| As described above, each type of stem cell fulfills a specific function in the body and cannot be expected to make cell types from other tissues. Thus, it is unlikely that a single type of stem cell treatment can treat multiple unrelated conditions, such as diabetes and Parkinsons disease. The underlying causes are very different and different cell types would need to be replaced to treat each condition. It is critical that the cell type used as a treatment be appropriate to the specific disease or condition.
Embryonic stem cells may one day be used to generate treatments for a range of human diseases. However, embryonic stem cells themselves cannot directly be used for therapies as they would likely cause tumors and are unlikely to become the cells needed to regenerate a tissue on their own. They would first need to be coaxed to develop into specialized cell types before transplantation. A major warning sign that a clinic may not be credible is when treatments are offered for a wide variety of conditions but rely on a single cell type. |
3. Currently, there are very few widely accepted stem cell therapies. |
| The range of diseases where stem cell treatments have been shown to be beneficial in responsibly conducted clinical trials is still extremely restricted. The best defined and most extensively used is blood stem cell transplantation to treat diseases and conditions of the blood and immune system, or to restore the blood system after treatments for specific cancers. Some bone, skin and corneal diseases or injuries can be treated with grafting of tissue that depends upon stem cells from these organs. These therapies are also generally accepted as safe and effective by the medical community. |
4. Just because people say stem cells helped them doesnt mean they did. |
| There are three main reasons why a person might feel better that are unrelated to the actual stem cell treatment: the placebo effect, accompanying treatments, and natural fluctuations of the disease or condition. The intense desire or belief that a treatment will work can cause a person to feel like it has and to even experience positive physical changes, such as improved movement or less pain. This phenomenon is called the placebo effect. Even having a positive conversation with a doctor can cause a person to feel improvement. Likewise, other techniques offered along with stem cell treatmentsuch as changes to diet, relaxation, physical therapy, medication, etc.may make a person feel better in a way that is unrelated to the stem cells. Also, the severity of symptoms of many conditions can change over time, resulting in either temporary improvement or decline, which can complicate the interpretation of the effectiveness of treatments. These factors are so widespread that without testing in a controlled clinical study, where a group that receives a treatment is carefully compared against a group that does not receive this treatment, it is very difficult to determine the real effect of any therapy. Be wary of clinics that measure or advertise their results primarily through patient testimonials. |
5. A large part of why it takes time to develop new therapies is that science itself is a long and difficult process. |
| Science, in general, is a long and involved process. Understanding what goes wrong in disease or injury and how to fix it takes time. New ideas have to be tested first in a research laboratory, and many times the new ideas dont work. Even once the basic science has been established, translating it into an effective medical treatment is a long and difficult process. Something that looks promising in cultured cells may fail as a therapy in an animal model and something that works in an animal model may fail when it is tried on humans. Once therapies are tested in humans, ensuring patient safety becomes a critical issue and this means starting with very few people until the safety and side effects are better understood. |
6. To be used in treatments, stem cells will have to be instructed to behave in specific ways. |
| Bone marrow transplantation is typically successful because we are asking the cells to do exactly what they were designed to do, make more blood. For other conditions, we may want the cells to behave in ways that are different from how they would ordinarily work in the body. One of the greatest barriers to the development of successful stem cell therapies is to get the cells to behave in the desired way. Also, once transplanted inside the body the cells need to integrate and function in concert with the bodys other cells. For example, to treat many neurological conditions the cells we implant will need to grow into specific types of neurons, and to work they will also have to know which other neurons to make connections with and how to make these connections. We are still learning about how to direct stem cells to become the right cell type, to grow only as much as we need them to, and the best ways to transplant them. Discovering how to do all this will take time. Be wary of claims that stem cells will somehow just know where to go and what to do to treat a specific condition. |
7. Just because stem cells came from your body doesnt mean they are safe. |
| Every medical procedure has risks. While you are unlikely to have an immune response to your own cells, the procedures used to acquire, grow and deliver them are potentially risky. As soon as the cells leave your body they may be subjected to a number of manipulations that could change the characteristics of the cells. If they are grown in culture (a process called expansion), the cells may lose the normal mechanisms that control growth or may lose the ability to specialize into the cell types you need. The cells may become contaminated with bacteria, viruses or other pathogens that could cause disease. The procedure to either remove or inject the cells also carries risk, from introducing an infection to damaging the tissue into which they are injected. |
8. There is something to lose by trying an unproven treatment. |
| Some of the conditions that clinics claim are treatable with stem cells are considered incurable by other means. It is easy to understand why people might feel they have nothing to lose from trying something even if it is unproven. However, there are very real risks of developing complications, both immediate and long-term, while the chance of experiencing a benefit is likely very low. In one publicized case, a young boy developed brain tumors as a result of a stem cell treatment. Participating in an unproven treatment may make a person ineligible to participate in upcoming clinical trials (see also number 9). Where cost is high, there may be long-term financial implications for patients, their families and communities. If travel is involved there are additional considerations, not the least of which is being away from family and friends. |
9. An experimental treatment offered for sale is not the same as a clinical trial. |
| The fact that a procedure is experimental does not automatically mean that it is part of a research study or clinical trial. A responsible clinical trial can be characterized by a number of key features. There is preclinical data supporting that the treatment being tested is likely to be safe and effective. Before starting, there is oversight by an independent group such as an Institutional Review Board or medical ethics committee that protect patients rights, and in many countries the trial is assessed and approved by a national regulatory agency, such as the European Medicines Agency (EMA) or the U.S. Food and Drug Administration (FDA). The study itself is designed to answer specific questions about a new treatment or a new way of using current treatments, often with a control group to which the group of people receiving the new treatment is compared. Typically, the cost of the new treatment and trial monitoring is defrayed by the company developing the treatment or by local or national government funding.Beware of expensive treatments that have not passed successfully through clinical trials.
Responsibly-conducted clinical trials are critical to the development of new treatments as they allow us to learn whether these treatments are safe and effective. The ISSCR supports participation in responsible clinical trials after careful consideration of the issues highlighted on this site and in discussion with a trusted physician.
For more information on clinical trials work click here |
10. Stem cell science is constantly moving forward. |
| Stem cell science is extraordinarily promising. There have been great advances in treating diseases and conditions of the blood system using blood-forming stem cells, and these show us just how powerful stem cell therapies can be. Scientists all over the world are researching ways to harness stem cells and use them to learn more about, to diagnose, and to treat various diseases and conditions. Every day scientists are working on new ways to shape and control different types of stem cells in ways that are bringing us closer to developing new treatments. Many potential treatments are currently being tested in animal models and some have already been brought to clinical trials. In February 2010 the British company ReNeuron announced it had been approved to conduct a Phase I clinical trial of a neural stem cell treatment for stroke. The first embryonic stem cell-based treatment for acute spinal cord injury is currently under review by the U.S. Food and Drug Administration (FDA) and will hopefully move into clinical trials soon. Although it is sometimes hard to see, stem cell science is moving forward. We are tremendously optimistic that stem cell therapies will someday be available to treat a wide range of human diseases and conditions. |
Spine Stimulation May Benefit Parkinson’s Disease Patients
Wednesday, June 23, 2010
By Steven Marsh
Patients who have been diagnosed with Parkinsons disease (PD) may have relief from symptoms associated with the condition in the near future, according to a study presented at the 2010 American Society for Stereotactical and Functional Neurosurgery.
In an effort to find potential treatments for individuals with the nervous system disorder, a team of researchers at Rhode Island Hospital conducted a series of exercises that stimulated the spinal cord on an animal model, which showed signs of PD. Because the findings displayed better motor function in the animal, the investigators tested the treatment with spinal cord simulation on a male patient aged 82 years.
While the individual wasn't receiving any form of medication as treatment for the disorder, researchers used different frequencies of stimulation to determine if a human would experience similar results compared to the animal model.
The researchers discovered that high stimulation frequencies made it easier for the patient to walk, while low frequencies worsened PD side effects.
While the results of thes tudy did give investigators some insight as to how to treat PD patients, clinical trials with a larger group of patients would be more beneficial to developing treatment.
Finding therapies for this disorder is growing in interest throughout the medical world, as QR Pharma and Massachusetts General Hospital have launched research to determine a way to block a protein associated the development of PD.ADNFCR-1960-ID-19845071-ADNFCR
The Pharmacist's Perspective on Treatment of Early-Stage Parkinson's Disease
Thursday, June 10, 2010
Jack J. Chen, PharmD, BCPS, CGP
The management of Parkinson'sdisease (PD) is complex and involves nonpharmacologic and pharmacologicinterventions for motor and nonmotor symptoms (see accompanying articleby Dr. Simuni). The aim of this article is to provide a greaterunderstanding of PD, treatment risks and benefits, and new developmentsin treatment approach that will allow clinicians, pharmacists, andallied healthcare personnel to better educate and care for patients withPD.
As PD progresses from early to advanced stages, medicationadjustments and increased numbers of medications should be expected.This article will focus on pharmacotherapy interventions for early-stagePD with an emphasis on safety and drug interactions. A discussion aboutearly interventions in PD, outcomes, and healthcare costs is availableelsewhere.[1] Discussions regarding advanced stage PD, management ofmotor complications, and pharmacotherapies for nonmotor symptoms of PDare beyond the scope of this article and are also availableelsewhere.[2]
The Patient With Early-Stage PD
An individualwith early-stage PD who has been recently diagnosed may present withmotor symptoms and absence of functional impairment or mild functionalimpairment (eg, clumsiness of the hands, mild deterioration inperformance of sports activities, a bothersome tremor, worsening ofhandwriting). An untreated patient with early-stage PD will have aUnified Parkinson's Disease Rating Scale (UPDRS) score of 20 to 30.
Thecurrent pharmacologic management paradigm for early-stage PD consistsof initiating 1 drug (ie, monotherapy) to provide symptomatic benefit.Drug therapy is typically initiated to address functional impairment.However, with the publication of the Attenuation of Disease progressionwith Azilect Given Once-daily (ADAGIO) study data, initiation ofrasagiline in recently diagnosed patients with early PD presentingwithout functional impairment is a plausible approach.
Inearly-stage PD, monoamine oxidase type B (MAO-B) inhibitors, dopamineagonists, and levodopa (with a decarboxylase inhibitor such ascarbidopa) all provide a sufficient magnitude of therapeutic effect. Inaddition to providing relief of tremor, rigidity, and/or slowness ofmovement, pharmacotherapy can also improve nonmotor symptoms such asfatigue in early PD and can improve experiences of daily living. Ifother symptoms such as constipation, depression, sexual dysfunction, andsleep disorders are present, adjunctive therapies that specificallytarget the symptom should also be considered.
Pharmacotherapy forEarly-Stage PD: Safety, Side Effects, Drug Interactions
Drugsafety and treatment-emergent side effects play a major role in guidingthe selection and adjustment of pharmacotherapy in PD. Healthcareprofessionals involved in the pharmacotherapy management anddistribution spectrum of PD should be concerned about the overall safetyof the medications in this population, the safety of polypharmacyregimens and their necessity (or lack thereof), drug interactions, andeducation of the patient and family about benefits and risks of themedication regimen. Pharmacists, in particular, are traditionally morefocused on drug safety and interactions as well as on providinginstructions on proper use of medications.
Levodopa
Levodopaprovides a robust magnitude of symptom relief effects. In patients withearly PD, common side effects of levodopa include nausea andsomnolence. Of note, hallucinations and psychosis are more common inpatients with advanced stage PD. There is concern about the gradualemergence of motor complications (such as dyskinesias and fluctuations)associated with dose escalation and treatment duration. Motorcomplications can arise quickly (within a few months) or slowly (after ayear or more). Although there are risk factors (eg, levodopa dose andtreatment duration, younger age), no method has been found to predictwhich patients will experience motor complications.
Thedevelopment of levodopa-associated motor complications has a significantimpact on clinicians, patients, and healthcare resources. Motorcomplications can be a challenge for clinicians to manage, can impairpatient health-related quality of life, and can increase direct healthcosts. Independent researchers and pharmaceutical manufacturers havedevoted time and resources toward understanding the pathophysiology ofmotor complications and developing interventions that have specificefficacy for motor complications (eg, apomorphine, entacapone,rasagiline, selegiline oral disintegrating tablets, and deep brainstimulation). Eventually all patients with PD will be prescribedlevodopa; however, in patients with early PD, other medications areavailable to provide adequate symptom relief without the risk for motorcomplications.
Pramipexole, ropinirole, and rasagiline are alsoindicated as monotherapy for PD. Clinicians and patients should engagein discussions about the relative risks and benefits of levodopatherapy, and patients should be allowed to make informed decisions.
DopamineAgonists
The dopamine agonists (pramipexole, ropinirole) providesufficient symptomatic effects for patients with early-stage PD and areless likely to cause motor complications. Side effects that areencountered by patients with early PD include nausea, somnolence, edemaof the extremities, orthostatic hypotension, and impulse controldisorders (ICDs). Of note, hallucinations may occur in patients withearly PD, but are more common in advanced stage PD or patients withcognitive impairment.
Postmarketing recognition of the potentialfor dopamine agonist-induced ICDs has attracted much concern amongclinicians who treat PD. ICDs can be a source of financial and familialstrain for the patient. Common examples include excessive gambling,preoccupation with pornography, overindulgence in purchasing unnecessaryitems, excessive hobbyism, and preoccupation with Internet activities.The prospect of this potentially disruptive side effect should becommunicated to the patient and family. Dopamine agonist-associated ICDsare not dose related and can also develop in patients receiving lowdaily doses for restless legs syndrome.
MAO-B Inhibitors
TheMAO-B inhibitors (rasagiline, selegiline) provide modest symptomaticrelief in patients with early PD. Of the available MAO-B inhibitors,rasagiline is the only one with labeling approved by the US Food andDrug Administration for monotherapy in PD. In addition, data from theADAGIO study (a large, randomized, controlled trial) suggest that earlyinitiation of rasagiline in patients with PD and the absence offunctional impairment confer more benefit than delaying therapy.
Rasagilineis well tolerated in patients with early PD. Treatment-emergent sideeffects are nonspecific and include flulike weakness and asthenia.Overall, rasagiline is notable for its lack of dopaminergic side effects(eg, nausea, orthostasis, somnolence). Postmarketing data indicate thatrasagiline can be safely administered without regard to meal content oftyramine (eg, in foods such as aged cheeses, red wine, sauerkraut).Based on clinical pharmacology studies, tyramine restriction is nolonger required or advocated by the FDA when rasagiline is initiated.Likewise, sympathomimetic amines (eg, ephedrine, phenylephrine,phenylpropanolamine, pseudoephedrine) and local anesthesia withsympathomimetic vasoconstrictors can be administered concomitantly.Although the concurrent use of antidepressants (with serotonergicactivity) is not contraindicated, benefits should be weighed against thepotential for serotonin syndrome. The STACCATO study is underway tobetter define the potential occurrence of serotonin syndrome withrasagiline and antidepressants.[3]
Patient and Family Education
Patientand family education is critical for the safe and successful use ofmedications in patients with PD. The patient/family should be counseledabout the adverse effects that are most likely to occur and when toreport them to the prescriber. For example, ICDs such as Internetgambling could go undetected by family and unreported by patients andresult in serious financial complications. Nausea, common with levodopaand dopamine agonists, is uncomfortable for patients, and in somecircumstances, may cause discontinuation of therapy prematurely ifpatients are not informed in advance about how to manage the effect. Thesame is true for other adverse effects such as somnolence andorthostatic hypotension. Educating patients and family members aboutpotential treatment-emergent side effects and the importance of seekingassistance can mitigate premature abandonment of the therapy and preventthe side effect from becoming more severe.
Patients and familiesshould be counseled about the drug's expected time to onset andresponse. Levodopa symptomatic benefit will be noted almost immediately(within a few doses or days). Dopamine agonists require initiation at alow (subtherapeutic) dose with gradual titration to a maintenance dose.This is done to minimize side effects. Thus, onset of a noticeableimprovement usually takes more than 2 weeks. The onset of noticeableimprovement with rasagiline may take several weeks, and the full effectmay not be seen for up to 8 to 12 weeks.
Lack of awarenessregarding a realistic onset of effect can lead to medication abandonment(because of the belief that the drug is ineffective) and polypharmacy(if other agents are prescribed to treat symptoms that have not yetresponded to the initial agent).
Patients and families should becounseled about the risks of self-discontinuing a drug for PD. Aworsening of motor symptoms would occur, and in some cases,discontinuation effects such as agitation, anxiety, diaphoresis,dysphoria, insomnia, or neuroleptic malignant syndrome may occur.
Parkinson'sdisease is a lifelong neurologic disorder. Patients will be onpharmacotherapy for the rest of their lives and will have manyencounters with professionals in healthcare. Early-stage, mildlyimpairing PD will progress over time to advanced stages, with severemotor impairment and nonmotor deficits. For patients with early-stage PDand their families, dealing with the diagnosis, learning about PD andits prognosis, and accepting the need for lifelong therapy can beoverwhelming. Clinicians, pharmacists, and allied healthcare personnelcan help patients and families dealing with PD by ensuring that theyreceive adequate medication information at the time a new prescriptionis written and again when it is dispensed. Patients should be assessedfor side effects, and the need for ongoing monitoring of medicationefficacy and potential side effects should be discussed with the family.
Summary
Patientswith early-stage PD will have many encounters with healthcareprofessionals during their lifetime. A better understanding of the motorand nonmotor symptoms of PD, risks and benefits of PD medications(Table), and drug-related complications will allow clinicians,pharmacists, and allied health professionals to better educate andmanage patients. Thoughtful consideration about the initiation ofpharmacotherapy for early-stage PD and information on realisticexpectations of efficacy and side effects can help prevent therapyabandonment and improve clinician-patient management of PD.
Supportedby an independent educational grant from Teva Neuroscience.
Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomi
Wednesday, June 02, 2010
Bxarone P, Poewe W, Albrecht S, Debieuvre C, Massey D, Rascol O, TolosaE, Weintraub D.
Department of Neurological Sciences, Universityof Naples Federico II and IDC Hermitage Capodimonte, Naples, Italy.barone@unina.it
Abstract
BACKGROUND: Depression is commonin patients with Parkinson's disease, but evidence on the efficacy ofantidepressants in this population is lacking. Because depression inpatients with Parkinson's disease might be related to dopaminergicdysfunction, we aimed to assess the efficacy of the dopamine agonistpramipexole for treatment of depressive symptoms in patients withParkinson's disease. METHODS: We did a 12-week randomised, double-blind,placebo-controlled (1:1 ratio) trial of pramipexole (0.125-1.0 mg threetimes per day) compared with placebo in patients with mild-to-moderateParkinson's disease. Patients from 76 centres in 12 European countriesand South Africa were included if they were on stable antiparkinsoniantherapy without motor fluctuations and had depressive symptoms (15-itemgeriatric depression scale score > or =5 and unified Parkinson'sdisease rating scale [UPDRS] part 1 depression item score > or =2).Patients were randomly assigned by centre in blocks of four by use of arandomisation number generating system. Clinical monitors, the principalinvestigator, and patients were masked to treatment allocation. Theprimary endpoint was change in Beck depression inventory (BDI) score andall treated patients who had at least one post-baseline efficacyassessment were included in the primary analysis. We also did apre-specified path analysis with regression models to assess therelation between BDI and UPDRS part 3 (motor score) changes. This trialis registered with ClinicalTrials.gov, number NCT00297778, and EudraCT,number 2005-003788-22. FINDINGS: Between March, 2006, and February,2008, we enrolled 323 patients. Of 296 patients randomly assigned topramipexole or placebo, 287 were included in the primary analysis: 139in the pramipexole group and 148 in the placebo group. BDI scoresdecreased by an adjusted mean 5.9 (SE 0.5) points in the pramipexolegroup and 4.0 (0.5) points in the placebo group (difference 1.9, 95% CI0.5-3.4; p=0.01, ANCOVA). The UPDRS motor score decreased by an adjustedmean 4.4 (0.6) points in the pramipexole group and 2.2 (0.5) points inthe placebo group (difference 2.2, 95% CI 0.7-3.7; p=0.003, ANCOVA).Path analysis showed the direct effect of pramipexole on depressivesymptoms accounted for 80% of total treatment effect (p=0.04). Adverseevents were reported in 105 of 144 patients in the pramipexole group and101 of 152 in the placebo group. Adverse events in the pramipexolegroup were consistent with the known safety profile of the drug.INTERPRETATION: Pramipexole improved depressive symptoms in patientswith Parkinson's disease, mainly through a direct antidepressant effect.This effect should be considered in the clinical management of patientswith Parkinson's disease. Copyright 2010 Elsevier Ltd. All rightsreserved.
Surgery as a Treatment Option
Monday, May 24, 2010
Surgery may include thalamotomy, pallidotomy or the placement of deep brain stimulation (DBS) devices. The DBS system maybe located in the thalamus, pallidum, or subthalamic nucleus. It is crucial that only appropriate patients be selected for surgery since all patients with Parkinson's disease are not suitable to undergo these procedures.
Choosing the Correct Medications
Monday, May 17, 2010
Once the diagnosis of Parkinson's Disease has been made, the nextdecision is whether a patient should receive anti-parkinsonianmedication, which depends on: - The degree of functional impairment
- The degree of cognitive impairment
- Ability to tolerate medication
- The advice of the attending physician
No two patients react the same way to a given drug; therefore, ittakes time and patience to find an appropriate medication and dosage toalleviate symptoms. Many approaches are available for achieving the proper balance ofanti-parkinson medication-treating symptoms effectively while minimizingunpleasant side effects. Many issues must be considered when makingmedication decisions. For various reasons, many people prefer to take as little medicationas possible, as late in the disease as possible, and most doctors preferto prescribe the least amount of medication necessary. Every personwith Parkinson's disease needs to follow a program of drug therapyspecifically designed for that individual. There are many reasons why a standard regimen of medications cannotbe applied across the board to everyone with Parkinson's disease. Thisis another reason why your physician should be experienced in thetreatment and management of Parkinson's disease.
Maryland Parkinson's Disease and Movement Disorders Center
Tuesday, May 11, 2010
Only in the last 30 years have dramatic breakthroughs been made inthe management of Parkinson's disease. Current treatment can significantly relieve people's symptoms and markedly improve their quality of life. Treatment OptionsTreatment for Parkinson's disease may include any or all of the following: The first stage of treatment for Parkinson's is an accurate diagnosis.This is tricky, as we have noted, particularly early in the disorder when distinguishing Parkinson's disease from other diseases with similar symptoms is particularly difficult. It may be helpful to see a neurologist who is experienced with what are called movement disorders. A movement disorder specialist has expertise in diagnosing and treating Parkinson's disease and related disorders. A visit to a movement disorder center may also be useful. Most such centers are connected with a department of neurology at a medical school, although some are freestanding clinics.
Singapore scientists develop zebrafish model for studying Parkinson's Disease
Tuesday, May 04, 2010
Singapore scientists develop zebra fish model for studying Parkinson's Disease
Scientists at the Genome Institute of Singapore (GIS), a biomedical research institute of the Agency for Science, Technology and Research (A*STAR), have recently developed a zebra fish model for Parkinson's disease that can be used for understanding the mechanism underlying its development. The knowledge gained will be helpful for future screening of new drugs to treat Parkinson's disease (PD).
This study describes the first zebra fish model for LRRK2 mutation-related PD. It is able to overcome some limitations of other animal models ofLRRK2 and demonstrates that zebra fish, a tropical freshwater fish that can often be found in aquariums, can be used to study the development of human diseases. Led by GIS Group Leader Dr Liu Jianjun, the finding was published in PLoS Genetics on April 22, 2010.
To explore the biological functions of LRRK2, the scientists studied this gene in zebra fish by blocking its normal function. This resulted in Parkinsonism-like phenotypes in zebra fish, including locomotive defects and loss of neurons, similar to those of PD patients. It was found from the study that the defects of the fish can be rescued by expressing the normal protein of LRRK2. Significantly, the administration of Levo-dopa(L-dopa), a compound that is widely used to treat PD, can also rescue the locomotive defects caused by the modification of the zebra fish LRRK2protein.
Parkinson's disease (PD) is a degenerative disease of the brain that often impairs motor skills, speech and other functions.The discovery of several gene mutations in affected patients clearly demonstrated the involvement of genetic factors in the development of PD. LRRK2 was discovered from previous studies by the same team of researchers to be one of the most important genetic causes of PD in the Asian population.
"This work shows how the use of a simple model system in fish can help decipher the root causes of a serious human disorder like Parkinson's disease, " said Professor Edison Liu,Executive Director of the GIS.
Dr Lim Kah Leong, Associate Professor of the National Neuroscience Institute and Duke-NUS Graduate Medical School, added "This novel and elegant study has illuminated the role of an otherwise poorly understood but important domain of LRRK2that is associated with an increased risk for Parkinson's disease amongst Asian populations. The use of zebra fish as a disease model is aclever approach. I am definitely pleased to note that our arsenal of experimental organisms for drug screening has expanded with this study."
The zebra fish model derived from this study serves as a vertebrate model suitable for large-scale drug screening and provides a good disease model for PD. Using a novel technology known as the Zinc-finger nucleases (ZFNs), further research is being carried out to generate additional mutations of zebra fish LRRK2 gene. Such mutated zebra fishes can be used for advancing investigation for the biological mechanism of PD and screening of new drugs for PD treatment.
More information:The research findings can be found in the April 22, 2010 print issue of PLoS GENETICS under the title "Deletion of the WD40 Domain of LRRK2 in Zebra fish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect".
Provided by Agency for Science, Technology and Research(A*STAR)
A Yeast Contribution For The Treatment Of Parkinson’s Disease
Wednesday, January 20, 2010
Scientists have just identified several molecules capable of reversingthe brain abnormalities of Parkinsons disease (PD), while alsouncovering new clues for its origin in a study just published in thejournal Disease Models and Mechanisms (1). PD is characterised byabnormal deposits of a brain protein called alpha-synuclein throughoutthe damaged brain regions, but exactly what they do there is not clear.The fact that their numbers and spreading are associated diseaseprogression has made them, however, a major point of interest in PDresearch. The work now published suggests that these deposits areactually a normal physiological process to purge unwanted proteins but,when overloaded, they can also cause of the cellular abnormalitiesseen in PD neurons and, ultimately, neural death. This would explainwhy the disease tends to appear later in life when the whole metabolism(including this mechanism) becomes less efficient, and also why neuronsare particularly susceptible as they are one of the few cells of thebody that are not replaced when old and less capable. The study uses ayeast model of PD showing once again the power of simple organismmodels in the understanding of extremely complex human diseases.
PDis neurodegenerative disease characterised by increasing motor problems- tremors, rigidity and balance and coordination problems - that canleave the patient incapable of perform the simplest of everyday task.Many patients also suffer from non-motor symptoms, including dementia.There is also widespread death of dopamine-producing (dopaminergic)neurons in a part of the brain called the substantia nigra. Sincedopamine acts as messenger between this region (the control centre) andother neurons around the body to ensure proper regulation of the bodysmovement, these deaths are believed to cause PD motor disability.
Althoughthe symptoms can be treated with dopamine replacement therapies, as thedisease progresses, they stop working and, more importantly, PD is,ultimately, incurable. With the spread of the disease throughout anincreasing aging human population bringing dramatic financial andsocial costs (who will take care of these millions of patients?), newtreatments and/or a cure are now being exhaustively researched.
Amajor focus of the research has been a brain protein of unknownfunction called alpha-synuclein. In fact, deposits of abnormally foldedalpha-synuclein (a certain folding is associated to the properfunctioning of each protein) are found in inclusions dispersed all overthe damaged brain areas of PD patients. The role of these inclusions indisease is not known with hypotheses ranging from having no importance,to contribute to neural death or even serve to avoid death by renderingharmless toxic misfolded proteins. What is known, however, is thatthese alpha-synuclein inclusions are excellent markers of diseaseprogression they accompany the brain degeneration.
In 2003Tiago Outeiro - a Portuguese scientist and one of the first authors ofthe new study - and Susan Lindquist the team leader in both studies created a yeast model of PD by inserting the alpha-synuclein gene inyeast, an organism that normally does not have the protein. Remarkably,this created in yeast some of the cellular abnormalities seen in PDaffected neurons. And as alpha-synuclein quantities increased, also thenumbers of inclusions containing the protein, in such a way that ledthe researchers to suggest that these were, in fact, a physiologicalprocess for getting rid of unwanted proteins. And that maybe PDappeared when the capacity of the system was exceed. This hypothesiswas supported by the fact that multiplications of the normalalpha-synuclein gene (leading to protein overproduction) were known tocause some forms of human PD, and also by the disease tendency for alate onset, probably due to an aging and less metabolically capablebody.
To test this possibility in the study now published,Linhui Julie Su, Pavan K. Auluck, Tiago Fleming Outeiro and SusanLindquist, working at the Whitehead Institute for Biomedical Research,Cambridge USA, created yet another yeast PD model this time with evenhigher levels of alpha-synuclein (High-syn) by inserting extra copiesof the gene in the yeast genome. This PD model was then compared withyeast producing none or intermediate levels of alpha-synuclein(Int-syn) (this last organism was the one used in the 2003 study)
Remarkably,the new High-syn yeast suffered from several more of the cellularabnormalities characteristic of PD than the Int-syn yeast. The newabnormalities included problems with mitochondria (the energy producingfactories of the cell) as well as accumulation of toxic free radicals,in addition to the abnormalities in lipid transport mechanisms alreadydetected in Int-syn yeast. Problems in mitochondria and accumulation offree radicals are particularly interesting as, although seen in many PDpatients, until now they had been impossible to link toalpha-synuclein.
Next, to exploit the fact that the new(High-syn ) yeast PD model shared so many cellular features with itshuman counterpart the researchers tried to look for possible therapies.For that Su, Auluck and Outeiro tested 115,000 bioactive (so known toaffect live cells) compounds and found several able to correct one ormore of the cellular abnormalities induced by the high levels ofalpha-synuclein. Not only that, but these molecules were also effectivetreating worm and mammals (rat) models of PD. Even more remarkably,they were capable of rescuing human dopaminergic neurons in a third PDmodel raising the possibility that they could be used to treat human PD.
Interestinglyseveral of these new potentially therapeutic molecules looked verysimilar, what led Su and colleagues to test them against each other tofind that, in fact, they acted on the same targets across the differentspecies tested. This was particularly important because it shows thatthe biological mechanisms affected by the over-accumulation ofalpha-synuclein are conserved throughout millions of years of evolution- from yeast to humans further supporting the hypothesis that PDresults from a dysfunction of basic cellular mechanisms.
Inconclusion Su, Auluck and Outeiros work supports the idea thataccumulation of alpha-synuclein in vesicles inside brain cells, sotypical of PD, is a normal physiological mechanism, most probably toget rid of abnormal proteins. Overload of this mechanism seems enoughto cause PD-like symptoms (after all in these yeast models the proteinis perfectly normal). Neurons are particularly susceptible not onlybecause they are not renewed throughout the organisms life, but alsobecause they have higher than normal requirements for both mitochondriaand lipid metabolism due to their highly energetic functions.
Thenew studys major breakthrough, however, is the identification ofseveral new compounds apparently capable of reversing the cellularabnormalities associated with PD and, as such, with potential to beused in treatments against the brain degeneration of PD.
Infact, at the moment the disease is believed to already affect astriking 3% of the population above 65 years old (more than 1 millionin the US, 1,2 millions in Europe) and in a world where life expectancyis steadily increasing, pushing PD numbers (by the age of 80 more than2 out of 100 people will have signs of the condition), any clues intothe disease mechanisms and possible treatments are crucial.
Still,much more work is needed before therapies can be developed The nextstep - says Tiago Outeiro - is to confirm these results in other PDmodels, even more similar to the human disease, to understand betterthe mechanisms and identify the molecules targets so they can, ifproven secure, be eventually tested in humans
Acid associated with gout 'could help Parkinson's sufferers'
Monday, January 11, 2010
By Kate Devlin,
Parkinsons disease progresses more slowly inpatients with naturally high levels of the acid which triggers gout,suggesting a possible new treatment for the disease.
Patientswith high levels of uric acid were a third less likely to needtreatment over the course of two years than those with low levels, theresults of a new study show.
Researchers are now testing whether increasing Parkinsons patients uric acid levels safely can help their condition.
An antioxidant, the acid is created naturally as we digest food.
But too much uric acid, or urate, can cause bouts of gout, an extremely painful joint condition, and kidney stones.
Dietsrich in liver, seafood and dried beans have been linked to high uricacid levels but researchers warn that because of the side effectspatients should not try to increase their urate levels themselves.
Asmaller study published last year also suggested that high uric acidlevels could slow the progression of Parkinsons Disease.
DrAlberto Ascherio, from the Harvard School of Public Health, who led thestudy, said: Only now we can be reasonably sure that the slower rateof progression in patients with higher concentrations of urate is realand not a chance occurrence."
However, the researchers stressthat they do not yet know if it is the acid itself which carries theprotective benefit or some other process of the body which producesuric acid as a by-product.
The latest research looked at 800 sufferers of the condition.
Thelink between high uric acid levels and a slower development of thedisease was less clear in women then men, the study found, however thismay be because women tend to have higher natural levels of the acid.
Theresearchers are now conducting a trial to give 90 patients a drug,inosine, which can elevate uric acid levels, to test whether they canbe safely raised and if this slows the speed of the disease.
"Becauseelevated urate levels have known health risks, including gout andkidney stones urate elevation should only be attempted in the contextof a closely monitored clinical trial in which potential benefits andrisks are carefully balanced," Dr Schwarzschild said.
Effects of chronic low dose rotenone treatment on human microglial cells
Monday, January 04, 2010
Author: Shamim ShaikhLouise Nicholson
Exposure to toxins /chemicals is considered to be a significant risk factor in thepathogenesis of Parkinson's disease (PD); one putative chemical is thenaturally occurring herbicide rotenone that is now used widely inestablishing PD models. We, and others, have shown that chronic lowdose rotenone treatment induces excessive accumulation of ReactiveOxygen Species (ROS), inclusion body formation and apoptosis indopaminergic neurons of animal and human origin.
Some studieshave also suggested that microglia enhance the rotenone inducedneurotoxicity. While the effects of rotenone on neurons are wellestablished, there is little or no information available on the effectof rotenone on microglial cells, and especially cells of human origin.
Theaim of the present study was to investigate the effects of chronic lowdose rotenone treatment on human microglial CHME-5 cells.
Methods:We have shown previously that rotenone induced inclusion body formationin human dopaminergic SH-SY5Y cells and therefore used these cells as acontrol for inclusion body formation in this study. SH-SY5Y and CHME-5cells were treated with 5nM rotenone for four weeks.
At the endof week 4, both cell types were analysed for the presence of inclusionbodies, superoxide dismutases and cell activation (only in CHME-5cells) using Haematoxylin and Eosin staining, immunocytochemical andwestern blotting methods. Levels of active caspases and ROS (both extraand intra cellular) were measured using biochemical methods.
Conclusion:The results suggest that chronic low dose rotenone treatment activateshuman microglia (cell line) in a manner similar to microglia of animalorigin as shown by others.
However human microglia releaseexcessive amounts of ROS extracellularly, do not show excessive amountsof intracellular ROS and active caspases and most importantly do notshow any protein aggregation or inclusion body formation. Humanmicroglia appear to be resistant to rotenone (chronic, low dose)induced damage.
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