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)

Reactive oxygen/nitrogen species are readily generated in vivo, playing roles in many physiological and pathological conditions, such as Alzheimer's disease and Parkinson's disease, by oxidatively modifying various proteins. Previous studies indicate that large conductance Ca(2+)-activated K(+) channels (BK(Ca) or Slo) are subject to redox regulation. However, conflicting results exist whether oxidation increases or decreases the channel activity. We used chloramine-T, which preferentially oxidizes methionine, to examine the functional consequences of methionine oxidation in the cloned human Slo (hSlo) channel expressed in mammalian cells. In the virtual absence of Ca(2+), the oxidant shifted the steady-state macroscopic conductance to a more negative direction and slowed deactivation. The results obtained suggest that oxidation enhances specific voltage-dependent opening transitions and slows the rate-limiting closing transition. Enhancement of the hSlo activity was partially reversed by the enzyme peptide methionine sulfoxide reductase, suggesting that the upregulation is mediated by methionine oxidation. In contrast, hydrogen peroxide and cysteine-specific reagents, DTNB, MTSEA, and PCMB, decreased the channel activity. Chloramine-T was much less effective when concurrently applied with the K(+) channel blocker TEA, which is consistent with the possibility that the target methionine lies within the channel pore. Regulation of the Slo channel by methionine oxidation may represent an important link between cellular electrical excitability and metabolism.
J Gen Physiol 2001 Mar
PMID:Oxidative regulation of large conductance calcium-activated potassium channels. 1122 29

Dopamine (DA) in combination with iron (Fe(2+)) has been demonstrated to induce apoptosis in neuronal-like PC12 cells by an oxidative stress mechanism. To get a better insight of cell death and protective mechanisms in DA/Fe(2+)-induced toxicity, we investigated the effects of DA/Fe(2+) and the antioxidant action of 17 beta-estradiol (E2) in peripheral blood lymphocytes (PBL). We found that DA/Fe(2+)-induces apoptosis in PBL via a hydrogen peroxide (H(2)O(2))-mediated oxidative mechanism, which in turn triggers a cascade of molecular events requiring RNA and de novo protein synthesis. We have also demonstrated that E2 prevents significantly DA/Fe(2+)-induced apoptosis in PBL by directly inhibiting the intracellular accumulation of peroxides generated by DA/Fe(2+)-reaction. This protective activity is independent of the presence or activation of the estrogen receptors (ERs). These data further support and validate our previous hypothesis that DA/Fe(2+)/H(2)O(2) could be a general mediator of oxidative stress through a common cell death mechanism in both neuronal and nonneuronal cells. These findings may be particularly relevant to the potential approaches to rescue and prolong the survival of neurons by estrogens in patients with Parkinson's disease (PD).
Gen Pharmacol 2000 Jul
PMID:17 beta-estradiol protects lymphocytes against dopamine and iron-induced apoptosis by a genomic-independent mechanism. Implication in Parkinson's disease. 1167 99

The average age of the world's population is increasing rapidly. The "graying of America" presents new opportunities and new challenges for improving the oral health of the elderly, particularly those afflicted with neurocognitive impairments. The dental problems associated with these conditions include but are not limited to a decrease in oral hygiene; difficulty in controlling and retaining dentures; xerostomia, which often is drug-associated, and consequential root caries, recurrent decay, and purposeless chewing. Parkinson's disease and Alzheimer's disease are the most prevalent type of progressive neurocognitive impairing illnesses, affecting millions of elderly Americans. As the adult population increases, a greater number of patients with these diagnoses will require dental care. Dental providers need to be aware of the special problems associated with the treatment of the older healthy subject and the neurocognitively impaired patient.
Gen Dent
PMID:Dental needs of the elderly in the 21st century. 1264 Aug 53

BACKGROUND: Psychoacoustics is a fascinating developing field concerned with the evaluation of the hearing sensation as an outcome of a sound or speech stimulus. Neuroaudiology with electrophysiologic testing, records the electrical activity of the auditory pathways, extending from the 8th cranial nerve up to the cortical auditory centers as a result of external auditory stimuli. Central Auditory Processing Disorders may co-exist with mental disorders and complicate diagnosis and outcome. DESIGN: A MEDLINE search was conducted to search for papers concerning the association between Central Auditory Processing Disorders and mental disorders. The research focused on the diagnostic methods providing the inter-connection of various mental disorders and central auditory deficits. MEASUREMENTS AND MAIN RESULTS: The medline research revealed 564 papers when using the keywords 'auditory deficits' and 'mental disorders'. 79 papers were referring specifically to Central Auditory Processing Disorders in connection with mental disorders. 175 papers were related to Schizophrenia, 126 to learning disabilities, 29 to Parkinson's disease, 88 to dyslexia and 39 to Alzheimer's disease. Assessment of the Central Auditory System is carried out through a great variety of tests that fall into two main categories: psychoacoustic and electrophysiologic testing. Different specialties are involved in the diagnosis and management of Central Auditory Processing Disorders as well as the mental disorders that may co-exist with them. As a result it is essential that they are all aware of the possibilities in diagnostic procedures. CONCLUSIONS: Considerable evidence exists that mental disorders may correlate with CAPD and this correlation could be revealed through psychoacoustics and neuroaudiology. Mental disorders that relate to Central Auditory Processing Disorders are: Schizophrenia, attention deficit disorders, Alzheimer's disease, learning disabilities, dyslexia, depression, auditory hallucinations, Parkinson's disease, alcoholism, anorexia and childhood mental retardation. Clinical awareness should be high in order for doctors of the two specialties, psychiatry and otorhinolaryngology-audiology to collaborate.
Ann Gen Hosp Psychiatry 2003 May 20
PMID:Contribution of psychoacoustics and neuroaudiology in revealing correlation of mental disorders with central auditory processing disorders. 1279 8

There is strong evidence that oxidative stress participates in the etiology of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. In the previous studies we have already shown that a combination of alpha-tocopherol and ascorbic acid protect neurons against tert-butyl hydroperoxide (t-BuOOH) induced neurotoxicity in different brain regions including hippocampus and mid brain. In this work, we examined the neuroprotective effect of low dose of adenosine against protein oxidation (protein carbonyls) in parallel with the level of reduced glutathione (GSH) in hippocampus and mid brain regions of mouse brain. The t-BuOOH was injected intraperitoneally in three concentrations (50, 100, 150 mg/kg b.w.) for 10 days. Results showed dose dependent increase in protein carbonyl (PC) in hippocampus and mid brain region. This increase was accompanied by a significant (p < 0.05) decline in GSH content in both brain regions of t-BuOOH treated mice. Adenosine (1 mg/kg b.w.) protected both hippocampus and mid brain neurons against protein oxidation as evidenced by reduction in protein carbonyl content. The GSH content was significantly (p < 0.05) increased after the treatment of adenosine in both brain regions. These data show that prior treatment with low dose of adenosine attenuates the oxidative protein damage with parallel increase in the GSH level in hippocampus and mid brain of t-BuOOH induced mice.
Gen Physiol Biophys 2003 Mar
PMID:Free radical induced increase in protein carbonyl is attenuated by low dose of adenosine in hippocampus and mid brain: implication in neurodegenerative disorders. 1287 Jun 99

Dental practices will see an increasing number of older patients as our population ages over the next decade. The following article describes a denture repair in a patient with Parkinson's disease. The patient and his caregiver were unable to make multiple trips to the clinic for treatment. The type of repair described in this article minimized the amount of expense and time required to repair the denture.
Gen Dent
PMID:Urgent denture repair in a medically compromised patient. 1577 25

Parkinson disease is the second most frequent neurodegenerative disorder after Alzheimer disease. A subset of genetic forms of Parkinson disease has been attributed to alpha-synuclein, a synaptic protein with remarkable chaperone properties. Synphilin-1 is a cytoplasmic protein that has been identified as a partner of alpha-synuclein (Engelender, S., Kaminsky, Z., Guo, X., Sharp, A. H., Amaravi, R. K., Kleiderlein, J. J., Margolis, R. L., Troncoso, J. C., Lanahan, A. A., Worley, P. F., Dawson, V. L., Dawson, T. M., and Ross, C. A. (1999) Nat. Gen. 22, 110-114), but its function remains totally unknown. We show here for the first time that synphilin-1 displays an antiapoptotic function in the control of cell death. We have established transient and stable transfectants overexpressing wild-type synphilin-1 in human embryonic kidney 293 cells, telecephalon-specific murine 1 neurons, and SH-SY5Y neuroblastoma cells, and we show that both cell systems display lower responsiveness to staurosporine and 6-hydroxydopamine. Thus, synphilin-1 reduces procaspase-3 hydrolysis and thereby caspase-3 activity and decreases poly(ADP-ribose) polymerase cleavage, two main indicators of apoptotic cell death. Furthermore, we establish that synphilin-1 drastically reduces p53 transcriptional activity and expression and lowers p53 promoter transactivation and mRNA levels. Interestingly, we demonstrate that synphilin-1 catabolism is enhanced by staurosporine and blocked by caspase-3 inhibitors. Accordingly, we show by transcription/translation assay that recombinant caspase-3 and, to a lesser extent, caspase-6 but not caspase-7 hydrolyze synphilin-1. Furthermore, we demonstrate that mutated synphilin-1, in which a consensus caspase-3 target sequence has been disrupted, resists proteolysis by cellular and recombinant caspases and displays drastically reduced antiapoptotic phenotype. We further show that the caspase-3-derived C-terminal fragment of synphilin-1 was probably responsible for the antiapoptotic phenotype elicited by the parent wild-type protein. Altogether, our study is the first demonstration that synphilin-1 harbors a protective function that is controlled by the C-terminal fragment generated by its proteolysis by caspase-3.
 ...
PMID:Caspase-3-derived C-terminal product of synphilin-1 displays antiapoptotic function via modulation of the p53-dependent cell death pathway. 1649 29

Delirium, depression and other psychiatric difficulties are commonly encountered by posttransplantation patients, and antipsychotic medicines are frequently used to treat these difficulties. This article reviews previous research data concerning the immunological effects of these medicines, with particular focus on the consequences of prolactin elevation. Unproven but of concern is that these effects may influence graft fate. Older antipsychotic medicines such as haloperidol and chlorpromazine have a high likelihood of elevating prolactin. Prolactin is an immunologically active molecule generally promoting bone marrow function. This may be of benefit post-stem-cell transplant, helping engraftment, but could further rejection of solid-organ transplants. Elevated prolactin is implicated in the facilitation of graft-versus-host disease. Aripiprazole is the antipsychotic medicine least likely to increase prolactin (and may actually decrease prolactin); risperidone, the most likely to increase prolactin. Olanzapine, quetiapine and ziprazadone are antipsychotic medicines with a lower likelihood of elevating prolactin. Older ("neuroleptic") antipsychotics, such as chlorpromazine, droperidol and haloperidol, perphenazine and many others, are likely to elevate serum prolactin. Among antidepressants, most serotonin reuptake inhibitors, with the exception of sertraline, can slightly elevate prolactin. The atypical (i.e., alone in their class) antidepressants bupropion and mirtazapine are prolactin neutral. The immunological consequences of psychiatric medicines should be considered when treating transplant patients for delirium, depression and thought disorders; in addition, if elevation of prolactin is thought to be of immunological importance during psychiatric treatment, then it should be monitored and treated. The dopamine agonists used to treat Parkinson's disease--bromocriptine, pergolide, pramipexole, ropinerole--usually reverse antipsychotic-induced prolactin increases without compromising psychiatric effectiveness.
Gen Hosp Psychiatry
PMID:Review of evidence that posttransplantation psychiatric treatment commonly affects prolactin levels and thereby influences graft fate. 1667 66

An overview of studies on the issue of dementia in Parkinson's disease shows that, over time, there has been an evolution in the perception of the magnitude of the problem and of its nature. Dementia seems today to be part of the disease. This change in the understanding of the disease can be accounted for by various methodological problems and by difficulties, on one hand, in the definition of dementia and its differentiation from other conditions, and, on the other hand, in the diagnosis of the disease itself in individual cases. Optimal therapeutic strategies are also examined, either based on cholinesterase inhibitors or antiparkinsonian drugs and symptomatic measures.
Ann Gen Psychiatry 2006 Aug 08
PMID:Phenomenology and management of cognitive and behavioral disorders in Parkinson's disease. Rise and logic of dementia in Parkinson's disease. 1689 6

This study investigates the prevalence and demographic characteristics of hypersexuality in Parkinson's disease (PD). Impulse control disorders in PD patients have been associated with dopamine agonist therapy. Moreover, hypersexuality and pathological gambling have been associated with males, while females may be inherently thought to be more likely to participate in compulsive shopping and binge-eating behaviors. In this study, a screening mail-in survey was sent to all PD patients at a single Movement Disorders Center. One hundred forty one of 400 (35.3%) research packets were returned completed. Fifteen of 141 patients met initial screening criteria for hypersexual behavior. After detailed interview, only 6/141 (4.3%) of PD patients met criteria for pathologic hypersexual behavior. These behaviors included: compulsive masturbation, prostitution, and paraphilias. Patients with a younger age of PD onset were more likely to exhibit hypersexual behavior. Unlike previous report, no significant association was found between hypersexuality and gender or dopamine agonist use. Rather, this study suggests that physicians should be vigilant for hypersexual behavior in all PD patients, regardless of gender and PD medication regimen. Ultimately, given the innate sensitivity of the topic and survey limitations, it is very likely that hypersexual behavior in our cohort, as it is in the general PD population, has been under-reported.
Int J Gen Med 2009 Jul 30
PMID:Prevalence of hypersexual behavior in Parkinson's disease patients: Not restricted to males and dopamine agonist use. 2036 Aug 87


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