Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Women undergoing chemotherapy for breast cancer are often administered dopamine antagonist adjuvant medications that may increase levels of prolactin potentially increasing the risk of cancer. Using nationwide computerized registers of death data for the years 1991 through 1996 we examined 12,430,473 deaths of persons over 40 years of age and extracted 144,364 cases with Parkinson's disease (PD), a dopamine deficient population. Patients with PD had lower rates of breast and other types of malignancies, even in the presence of depression and suicide.
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PMID:Are dopamine antagonists a risk factor for breast cancer? An answer from Parkinson's disease. 1465 14

Mapping of the human and other eukaryotic genomes has provided the pharmacological industry with excellent models for drug discovery. Control of cell proliferation, differentiation, activation and cell removal is crucial for the development and existence of multicellular organisms. Each cell cycle progression, with sequences of DNA replication, mitosis, and cell division, is a tightly controlled and complicated process that, when deregulated, may become dangerous not only to a single cell, but also to the whole organism. Regulation and the proper control of the cell cycle and of programmed cell death (apoptosis) is therefore essential for mammalian development and the homeostasis of the immune system. The molecular networks that regulate these processes are critical targets for drug development, gene therapy, and metabolic engineering. In addition to the primary, intracellular apoptotic suicide machinery, components of the immune system can detect and remove cells and tissue fragments that no longer serve their defined functions. In this review we will focus on apoptotic pathways converging on caspase family proteases, summarizing pharmacological attempts that target genes, proteins, and intermolecular interactions capable of modulating apoptosis and the inflammatory response. The upcoming pharmacological development for treatment of acute pathologies, such as sepsis, SIRS, stroke, traumatic brain injury, myocardial infarction, spinal cord injury, acute liver failure, as well as chronic disorders such as Huntington's disease, Parkinson's disease, ALS, and rheumatoid arthritis, will be discussed in details. We also suggest new potential molecular targets that may prove to be effective in controlling apoptosis and the immune response in vivo.
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PMID:Stroke, myocardial infarction, acute and chronic inflammatory diseases: caspases and other apoptotic molecules as targets for drug development. 1524 81

Clozapine was one of the major advances in the treatment of schizophrenia since the introduction of the classic antipsychotic agent chlorpromazine in the 1950s. Over the past 10 years, clozapine has become the reference compound for the development of new antipsychotics, and new drugs have been developed which have also claimed atypical status. The indications of clozapine were recently extended to Psychosis in Parkinson's disease and harmonized in the European Union. This provides the opportunity to update the data on clozapine in the treatment of schizophrenia. In this article we review current clinical evidence in schizophrenia to address the following issues: 1) Efficacy in refractory/positive symptoms: a systematic and critical analysis of 14 double-blind clinical trials in comparison with both standard and novel antipsychotics show consistent findings in favour of clozapine, with all but three of the reports demonstrating superiority. The review of studies allow us to say little about the predictors of treatment response, time to clozapine response and about the impact of clozapine on the quality of patients'life and longer-term outcome. Treatment options for clozapine non-responders are reviewed. 2) Risk of EPS: clozapine is considered to have a minimal risk of EPS and in all studies where a valid methodology was used, a clear superiority over the other neuroleptics is demonstrated. It is pointed out that, if the prevalence and incidence of EPS with clozapine is low, it is not zero. All the studies assessing clozapine treatment for TD have major methodological limitations, so no final conclusion can be drawn. 3) Efficacy for primary and secondary negative symptoms and neurocognitive effects: the data of clinical studies where negative symptoms scales were used favour clozapine in terms of improvement. However most of the studies were carried out in populations with predominantly positive symptoms. With regard to the need to distinguish primary and secondary symptoms, data are conflicting regarding the benefit of clozapine. Due to the lack of studies with a valid methodology, no definitive conclusion can be drawn about the efficacy on clozapine on the deficit syndrome and on neurocognitive disorders. 4) Impact on suicide risk: 4 out of 6 retrospective studies provide evidence for the ability of clozapine therapy to reduce suicidal behaviour. The results of a recent randomized, parallel-group study designed to compare clozapine versus olanzapine in preventing suicide attempts seems to confirm this hypothesis. We also address the tolerability and safety data, especially haematologic, comitial, cardiovascular and metabolic side-effects. The effectiveness of blood monitoring for the management of neutropenia and agranulocytosis demands that the recommendations are strictly followed. The use of clozapine at doses higher than 600 mg daily should follow published recommendations, in order to minimize the risk of seizures; these include anticonvulsant regimens based on blood levels. With regard to the cardiovascular mortality, if clozapine therapy has negligible effects on QT interval, its association with potential fatal myocarditis cannot be excluded in young patients who should be investigated if they develop cardiac symptoms in the first weeks of treatment. Available data support the notion that the frequency of bodyweight gain is high with several new antipsychotics, including clozapine. Potential long term effects of bodyweight gain on mortality and morbidity have to be taken into consideration. The pharmacological mechanisms underlying the "unique clozapine profile" is discussed. Clozapine remains the only antipsychotic with efficacy at relatively low D2 receptor occupancy. The pharmacogenetic and pharmacokinetic aspects are also reviewed. Finally, the place of clozapine in the current treatment of schizophrenia is highlighted to inform the development of guidelines for clinical management.
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PMID:[Leponex, 10 years after -- a clinical review]. 1562 52

For the last nine years of his life Adolf Hitler, a lifelong hypochondriac had as his physician Dr Theodor Morell. Hitler's mood swings, Parkinson's disease, gastro-intestinal symptoms, skin problems and steady decline until his suicide in 1945 are documented by reliable observers and historians, and in Morell's diaries. The bizarre and unorthodox medications given to Hitler, often for undisclosed reasons, include topical cocaine, injected amphetamines, glucose, testosterone, estradiol, and corticosteroids. In addition, he was given a preparation made from a gun cleaner, a compound of strychnine and atropine, an extract of seminal vesicles, and numerous vitamins and 'tonics'. It seems possible that some of Hitler's behaviour, illnesses and suffering can be attributed to his medical care. Whether he blindly accepted such unorthodox medications or demanded them is unclear.
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PMID:Adolf Hitler's medical care. 1582 45

Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease trigger neuronal cell death through endogenous suicide pathways. Surprisingly, although the cell death itself may occur relatively late in the course of the degenerative process, the mediators of the underlying cell-death pathways have shown promise as potential therapeutic targets.
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PMID:Cell death in the nervous system. 1705 Dec 6

Patients with advanced Parkinson's disease (PD) experience worsening motor fluctuations and dyskinesia. Management options include deep brain stimulation of the subthalamic nucleus (STN-DBS), subcutaneous apomorphine (in combination with oral levodopa) or continuous duodenal levodopa administration. We have used all three therapies at our clinic in Milan and report our experience. Apomorphine infusion reduced daily off time but did not improve dyskinesia; long-term treatment was associated with impulse control disorders. STN-DBS provided motor benefit, but was associated with behavioural changes including attempted suicide. Duodenal levodopa produced significant clinical benefit without behavioural changes and allowed patients to discontinue all other PD medications. Duodenal levodopa should be considered in PD patients with advanced disease.
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PMID:Continuous dopaminergic stimulation--from theory to clinical practice. 1770 32

Deep brain stimulation (DBS) has been approved by the FDA for use in the treatment of Parkinson's disease, essential tremor, and dystonia. Case reports and case series have reported significant psychiatric side effects in some individuals. The goal of this meta-analysis is to characterize the risks and benefits of DBS and to assess its possible use within the psychiatric setting. A search was conducted on PubMed, EBSCO, and PsycInfo in January 2006 that covered the time period 1 Jan 1996-30 Dec 2005. All identified articles were reviewed and those describing adverse events were further examined with a structured instrument. The initial searches yielded 2667 citations; 808 articles met inclusion criteria for the meta-analysis; 98.2% of studies that specifically assessed motor function reported some level of improvement. Most reported side effects were device or procedure related (e.g., infection and lead fracture). The prevalence of depression was 2-4%, mania 0.9-1.7%, emotional changes 0.1-0.2%, and the prevalence of suicidal ideation/suicide attempt was 0.3-0.7%. The completed suicide rate was 0.16-0.32%. In conclusion, DBS is an effective treatment for Parkinson's disease, dystonia, and essential tremor, and case reports suggest that major depression and OCD may also respond to DBS. Reported rates of depression, cognitive impairment, mania, and behavior change are low, but there is a high rate of suicide in patients treated with DBS, particularly with thalamic and GPi stimulation. Because of the high suicide rate, patients should be prescreened for suicide risk prior to DBS surgery. Additionally, patients should be monitored closely for suicidal behavior post-operatively.
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PMID:Psychiatric and neuropsychiatric adverse events associated with deep brain stimulation: A meta-analysis of ten years' experience. 1858 79

Akathisia is a neurological side effect of antipsychotic medications, which are used to treat various psychiatric disorders, and is characterized by physical restlessness and a subjective urge to move. Although side effects, such as akathisia, dystonia, and dyskinesia, are common for conventional medications, these effects occur in reduced frequency with the use of new-generation antipsychotics. Despite a lowered incidence profile, akathisia and similar conditions continue to affect patients. Neuroleptic-induced akathisia can present as fidgety movements while seated, rocking in place while standing, pacing, or the inability to sit or stand still for an extended period of time as well as the overwhelming urge to move, which can cause severe distress and an increased risk of suicide for affected patients. First-line treatment of akathisia includes benzodiazepines or beta-blockers for patients who do not have symptoms of Parkinson's disease and anticholinergics for patients with Parkinson's symptoms. Clinicians should ensure that an accurate diagnosis of akathisia is made and target symptoms are decreasing due to treatment, which does not negatively affect the mental health of the patient. This expert roundtable supplement will address the diagnosis, pathophysiology, phenomenology, classification, and history of akathisia as well as provide screening tools and treatment options for the condition.
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PMID:Akathisia: problem of history or concern of today. 1780 18

Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative diseases that affect different parts of the central nervous system. However, a review of the literature indicates that certain biochemical reactions involved in neurodegeneration in these three diseases are quite similar and could be partly identical. This article critically examines the similarities and, based on data from our own and other laboratories, proposes a novel explanation for neurodegeneration in these three diseases. We identified about 20 commonalities that exist in the neurodegenerative process of each disease. We hypothesize that there are two enzyme-catalyzed pathways that operate in affected neurons: an oxidative pathway leading to destruction of various neuronal proteins and lipids, and an apoptotic pathway which the body normally uses to remove unwanted and dysfunctional cells. Data from many laboratories indicate that oxidative reactions are primarily responsible for neurodegeneration, whereas apoptosis may well be a secondary response to the presence of neurons that have already been severely damaged by oxidative reactions. Attempts to inhibit apoptosis for the purpose of attenuating progression of these diseases may therefore be only of marginal benefit. Specific oxidative reactions within affected neurons led us to propose that one or more heme peroxidases may be the catalyst(s) involved in oxidation of proteins and lipids. Support for this proposal is provided by the recent finding that amyloi-beta peptide may act as a peroxidase in AD. Possible participation of the peroxidase activity of cytochrome c, herein designated as cytochrome c(px) to distinguish it from yeast cytochrome c peroxidase, is discussed. Of special interest is our recent finding that many compounds that cause attenuation of neurodegeneration are inhibitors of the peroxidase activity of cytochrome c. Several inhibitors were subsequently identified as suicide substrates. Such inhibitors could be ideally suited for targeted clinical approaches aimed at arresting progression of neurodegeneration. Finally, it is possible that immobilized yet still active peroxidase(s) may be present in protein aggregates in AD, PD, and ALS. This activity could be the catalyst for the slow, self-perpetuating and irreversible degeneration of affected neurons that occurs over long periods of time in these neurodegenerative diseases.
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PMID:Neurodegeneration and peroxidases. 1805 17

The validity, sensitivity, and specificity of depressive symptoms for the diagnosis of major depression, minor depression, dysthymic disorder, and subsyndromal depression in Parkinson's disease (PD) were examined. A consecutive series of 173 patients with PD attending a Movement Disorders Clinic underwent a comprehensive psychiatric and neurological assessment. The symptoms of loss of interest/pleasure, changes in appetite or weight, changes in sleep, low energy, worthlessness or inappropriate guilt, psychomotor retardation/agitation, concentration deficits, and suicide ideation were all significantly associated with the presence of the DSM-IV depressed mood criterion for major depression. The symptoms of changes in appetite, changes in sleep, low energy, low self-esteem, poor concentration, and hopelessness were all significantly associated with the presence of the DSM-IV criterion of sad mood for dysthymic disorder. Thirty percent of our sample met DSM-IV diagnostic criteria for major depression, 20% met diagnostic criteria for dysthymic disorder, 10% met diagnostic criteria for minor depression, and 8% met clinical criteria for subsyndromal depression. Patients with either major or minor depression had significantly more severe deficits in activities of daily living, more severe cognitive impairments, and more severe Parkinsonism than patients with either dysthymic disorder or no depression. This study provides validation to the DSM-IV diagnostic criteria for major depression and dysthymic disorder for use in PD. The categories of minor and subsyndromal depression may need further validation.
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PMID:A validation study of depressive syndromes in Parkinson's disease. 1807 76


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