Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Studies have shown that parkinsonian signs are related to cognitive function in aging. What remains unclear is whether this association is stronger for some cognitive domains than it is for others, and precisely how much variability in global and specific cognitive functions is explained by the motor signs. We examined the associations between four parkinsonian signs (gait, rigidity, bradykinesia, tremor) and five cognitive domains (episodic memory, semantic memory, working memory, perceptual speed, visuospatial ability) in a large cohort of older persons who were free of Parkinson's disease and dementia and were participating in the Rush Memory and Aging Project. In a series of regression equations that controlled for age, sex, and education, higher levels of three signs (gait, rigidity, and bradykinesia) were related to lower levels of cognitive function, but they accounted for less than 5% of the variance in most measures. The results did not change when the presence of depressive symptoms, diabetes, and hypertension were added to the models. The cross-sectional association between parkinsonian signs and cognitive function did not vary substantially across specific cognitive domains or specific cognitive tests. The results suggest that parkinsonian signs have a modest, but statistically reliable, association with level of cognitive function in old age.
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PMID:Parkinsonian signs and cognitive function in old age. 1621 86

Patients with Parkinson disease often have orthostatic hypotension. Neurocirculatory abnormalities underlying orthostatic hypotension might reflect levodopa treatment. Sixty-six Parkinson disease patients (36 with orthostatic hypotension, 15 off and 21 on levodopa; 30 without orthostatic hypotension) had tests of reflexive cardiovagal gain (decrease in interbeat interval per unit decrease in systolic pressure during the Valsalva maneuver; orthostatic increase in heart rate per unit decrease in pressure); reflexive sympathoneural function (decrease in pressure during the Valsalva maneuver; orthostatic increment in plasma norepinephrine); and cardiac and extracardiac noradrenergic innervation (septal myocardial 6-[18F]fluorodopamine-derived radioactivity; supine plasma norepinephrine). Severity of orthostatic hypotension did not differ between the levodopa-untreated and levodopa-treated groups with Parkinson disease and orthostatic hypotension (-52+/-6 [SEM] versus -49+/-5 mm Hg systolic). The 2 groups had similarly low reflexive cardiovagal gain (0.84+/-0.23 versus 1.33+/-0.35 ms/mm Hg during Valsalva; 0.43+/-0.09 versus 0.27+/-0.06 bpm/mm Hg during orthostasis); and had similarly attenuated reflexive sympathoneural responses (97+/-29 versus 71+/-23 pg/mL during orthostasis; -82+/-10 versus -73+/-8 mm Hg during Valsalva). In patients off levodopa, plasma norepinephrine was lower in those with (193+/-19 pg/mL) than without (348+/-46 pg/mL) orthostatic hypotension. Low values for reflexive cardiovagal gain, sympathoneural responses, and noradrenergic innervation were strongly related to orthostatic hypotension. Parkinson disease with orthostatic hypotension features reflexive cardiovagal and sympathoneural failure and cardiac and partial extracardiac sympathetic denervation, independent of levodopa treatment.
Hypertension 2005 Dec
PMID:Neurocirculatory abnormalities in Parkinson disease with orthostatic hypotension: independence from levodopa treatment. 1621 82

The serotonin (5-hydroxytryptamine) 5-HT2 receptor subfamily consists of three members, 5-HT2A, 5-HT2B, and 5-HT2C. These receptors share high homology in their amino acid sequence, have similar signaling pathways, and have been indicated to play important roles in feeding, anxiety, aggression, sexual behavior, mood, and pain. Subtype-selective agonists and antagonists have been explored as drugs for hypertension, Parkinson's disease, sleep disorders, anxiety, depression, schizophrenia, and obesity. In this study, we report the development of homogeneous agonist binding assays in a scintillation proximity assay (SPA) format to determine the high-affinity binding state of agonist compounds for the human 5-HT2C, 5-HT2A, and 5-HT2B receptors. The 5-HT2 agonist 1-(4- [125I]iodo-2,5-dimethoxyphenyl)-2-aminopropane ([125I]DOI) was used to label the high-affinity sites for the 5-HT2A and 5-HT2C receptors. The high-affinity sites for the 5-HT2B receptor were labeled with [3H]lysergic acid diethylamide. Total receptor expression was determined with the 5-HT2 antagonist [3H]mesulergine for the 5-HT2B and 5-HT2C receptors, and [3H]ketanserin for the 5-HT2A receptor. The agonist high-affinity binding sites accounted for 2.3% (5-HT(2C) receptor), 4.0% (5-HT2A receptor), and 22% (5-HT2B receptor) of the total receptor population. Competition binding studies using known agonists indicated high Z' values of the agonist binding assays in SPA format (Z' > 0.70). The Ki values of 5-HT, (R)(-)DOI, and VER-3323 for the 5-HT2A, 5-HT2B, and 5-HT2C receptors by SPA format were equivalent to published data determined by filtration binding assays. These results indicate that agonist binding assays in SPA format can be easily adapted to a high throughput assay to screen for selective 5-HT2C receptor agonists, as well as for selectivity profiling of the compounds.
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PMID:Development of homogeneous high-affinity agonist binding assays for 5-HT2 receptor subtypes. 1643 60

Coffee is a complex mixture of chemicals that provides significant amounts of chlorogenic acid and caffeine. Unfiltered coffee is a significant source of cafestol and kahweol, which are diterpenes that have been implicated in the cholesterol-raising effects of coffee. The results of epidemiological research suggest that coffee consumption may help prevent several chronic diseases, including type 2 diabetes mellitus, Parkinson's disease and liver disease (cirrhosis and hepatocellular carcinoma). Most prospective cohort studies have not found coffee consumption to be associated with significantly increased cardiovascular disease risk. However, coffee consumption is associated with increases in several cardiovascular disease risk factors, including blood pressure and plasma homocysteine. At present, there is little evidence that coffee consumption increases the risk of cancer. For adults consuming moderate amounts of coffee (3-4 cups/d providing 300-400 mg/d of caffeine), there is little evidence of health risks and some evidence of health benefits. However, some groups, including people with hypertension, children, adolescents, and the elderly, may be more vulnerable to the adverse effects of caffeine. In addition, currently available evidence suggests that it may be prudent for pregnant women to limit coffee consumption to 3 cups/d providing no more than 300 mg/d of caffeine to exclude any increased probability of spontaneous abortion or impaired fetal growth.
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PMID:Coffee and health: a review of recent human research. 1650 75

Voluntary physical activity and exercise training can favorably influence brain plasticity by facilitating neurogenerative, neuroadaptive, and neuroprotective processes. At least some of the processes are mediated by neurotrophic factors. Motor skill training and regular exercise enhance executive functions of cognition and some types of learning, including motor learning in the spinal cord. These adaptations in the central nervous system have implications for the prevention and treatment of obesity, cancer, depression, the decline in cognition associated with aging, and neurological disorders such as Parkinson's disease, Alzheimer's dementia, ischemic stroke, and head and spinal cord injury. Chronic voluntary physical activity also attenuates neural responses to stress in brain circuits responsible for regulating peripheral sympathetic activity, suggesting constraint on sympathetic responses to stress that could plausibly contribute to reductions in clinical disorders such as hypertension, heart failure, oxidative stress, and suppression of immunity. Mechanisms explaining these adaptations are not as yet known, but metabolic and neurochemical pathways among skeletal muscle, the spinal cord, and the brain offer plausible, testable mechanisms that might help explain effects of physical activity and exercise on the central nervous system.
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PMID:Neurobiology of exercise. 1664 3

Treatment of migraine presents special problems in the elderly. Co-morbid diseases may prohibit the use of some medications. Moreover, even when these contraindications do not exist, older patients are more likely than younger ones to develop adverse events. Managing older migraine patients, therefore, necessitates particular caution, including taking into account possible pharmacological interactions associated with the greater use of drugs for concomitant diseases in the elderly. Paracetamol (acetaminophen) is the safest drug for symptomatic treatment of migraine in the elderly. Use of selective serotonin 5-HT(1B/1D) receptor agonists ('triptans') is not recommended, even in the absence of cardiovascular or cerebrovascular risk, and NSAID use should be limited because of potential gastrointestinal adverse effects. Prophylactic treatments include antidepressants, beta-adrenoceptor antagonists, calcium channel antagonists and antiepileptics. Selection of a drug from one of these classes should be dictated by the patient's co-morbidities. Beta-adrenoceptor antagonists are appropriate in patients with hypertension but are contraindicated in those with chronic obstructive pulmonary disease, diabetes mellitus, heart failure and peripheral vascular disease. Use of antidepressants in low doses is, in general, well tolerated by elderly people and as effective, overall, as in young adults. This approach is preferred in patients with concomitant mood disorders. However, prostatism, glaucoma and heart disease make the use of tricyclic antidepressants more difficult. Fewer efficacy data in the elderly are available for selective serotonin reuptake inhibitors, which can be tried in particular cases because of their good tolerability profile. Calcium channel antagonists are contraindicated in patients with hypotension, heart failure, atrioventricular block, Parkinson's disease or depression (flunarizine), and in those taking beta-adrenoceptor antagonists and monoamine oxidase inhibitors (verapamil). Antiepileptic drug use should be limited to migraine with high frequency of attacks and refractoriness to other treatments. Promising additional strategies include ACE inhibitors and angiotensin II type 1 receptor antagonists because of their effectiveness and good tolerability in patients with migraine, particularly in those with hypertension. Because of its favourable compliance and safety profile, botulinum toxin type A can be considered an alternative treatment in elderly migraine patients who have not responded to other currently available migraine prophylactic agents. Pharmacological treatment of migraine poses special problems in regard to both symptomatic and prophylactic treatment. Contraindications to triptan use, adverse effects of NSAIDs, and unwanted reactions to some antiemetics reduce the list of drugs available for the treatment of migraine attacks in elderly patients. The choice of prophylactic treatment (beta-adrenoceptor antagonists, calcium channel antagonists, antiepileptics, and more recently, some antihypertensive drugs) is influenced by co-morbidities and should be directed at those drugs that are believed to have fewer adverse effects and a better safety profile. Unfortunately, for most of these drugs, efficacy studies are lacking in the elderly.
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PMID:Practical considerations for the treatment of elderly patients with migraine. 1687 31

Blood pressure disorders are highly prevalent in the course of Parkinson's disease (PD). They relate to autonomic failure and are frequently associated with orthostatic hypotension, postprandial hypotension and supine hypertension. Supine hypertension, which may concern up to 50% of patients with PD and autonomic failure, is driven by residual sympathetic activity and changes in sensitivity of vascular adrenergic receptors. It can also be induced or worsened by antihypotensive drugs. Even if little data is available, a set of arguments suggests that supine hypertension sometimes requires treatment. This review will focus on recent data on the pathophysiology and the management of supine hypertension in the context of its association with orthostatic hypotension.
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PMID:Blood pressure disorders during Parkinson's disease: epidemiology, pathophysiology and management. 1689 45

Reactive oxygen species (ROS) and reactive nitrogen species (RNS, e.g. nitric oxide, NO(*)) are well recognised for playing a dual role as both deleterious and beneficial species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. Overproduction of ROS (arising either from mitochondrial electron-transport chain or excessive stimulation of NAD(P)H) results in oxidative stress, a deleterious process that can be an important mediator of damage to cell structures, including lipids and membranes, proteins, and DNA. In contrast, beneficial effects of ROS/RNS (e.g. superoxide radical and nitric oxide) occur at low/moderate concentrations and involve physiological roles in cellular responses to noxia, as for example in defence against infectious agents, in the function of a number of cellular signalling pathways, and the induction of a mitogenic response. Ironically, various ROS-mediated actions in fact protect cells against ROS-induced oxidative stress and re-establish or maintain "redox balance" termed also "redox homeostasis". The "two-faced" character of ROS is clearly substantiated. For example, a growing body of evidence shows that ROS within cells act as secondary messengers in intracellular signalling cascades which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. This review will describe the: (i) chemistry and biochemistry of ROS/RNS and sources of free radical generation; (ii) damage to DNA, to proteins, and to lipids by free radicals; (iii) role of antioxidants (e.g. glutathione) in the maintenance of cellular "redox homeostasis"; (iv) overview of ROS-induced signaling pathways; (v) role of ROS in redox regulation of normal physiological functions, as well as (vi) role of ROS in pathophysiological implications of altered redox regulation (human diseases and ageing). Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing. Topics of current debate are also reviewed such as the question whether excessive formation of free radicals is a primary cause or a downstream consequence of tissue injury.
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PMID:Free radicals and antioxidants in normal physiological functions and human disease. 1697 5

It is projected that, in the 21st century, the majority of the world's older people will be living in Asia. After Japan, Singapore is the most rapidly aging country in Asia. With an increasing life expectancy, many older persons will require health and instrumental care during later life stages. In Singapore, close to 95% of older people co-reside with family members, highlighting the importance of community support for family caregivers. Using a study of 61 principal family caregivers in Singapore, this article highlights the nature of and relationship between caregivers' stress and gender, patients' activities of daily living (ADL) and instrumental ADL dependency, and caregivers' attitudes. Findings from the study suggest that female caregivers tended to be more stressed than male caregivers. Results also showed a significant inverse relationship between the level of stress experienced by caregivers and the ADL and instrumental ADL dependency of patients. Caregivers looking after patients suffering from dementia, Parkinson's disease, and hypertension were more likely to be stressed than those caring for persons with stroke, depression, and other illnesses. This article concludes by describing some implications of this research for social worker practice and for informal as well as formal support programs for family caregivers.
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PMID:Stress among family caregivers of older persons in Singapore. 1702 77

Cardiac autonomic abnormalities have been described in Parkinson's disease. Little is known about possible alterations of vascular sympathetic regulatory activity in patients without orthostatic hypotension or symptoms of orthostatic intolerance. Nineteen patients with Parkinson's disease without orthostatic hypotension (PD), 21 with orthostatic hypotension (PDOH), and 20 healthy controls underwent ECG, beat-to-beat arterial pressure, and respiration recordings while recumbent and during a 75 degrees head-up tilt. Spectrum analysis of RR interval and systolic arterial pressure (SAP) variability provided indices of cardiac sympathovagal interaction (low frequency [LF]/high frequency [HF]) to the sinoatrial node and sympathetic vasomotor control (LF(SAP)). Arterial baroreceptor mechanisms were assessed by the spontaneous sequences technique and bivariate spectrum analysis (alpha index). Plasma catecholamines provided the neurohormonal profile. At rest, hemodynamics and spectral markers of autonomic function were similar in PD and control subjects. Norepinephrine was lower in PD and PDOH than in control subjects. In PDOH, SAP was higher, whereas LF/HF ratio and LF(SAP) were lower compared with control subjects. During tilt, SAP was unchanged in PD; however, similar to PDOH, the increase of heart rate, LF/HF ratio, and LF(SAP) was blunted compared with control subjects. Baroreflex indices were unmodified in PD and PDOH compared with control subjects. Initial alterations in both cardiac and vascular sympathetic modulatory activity were found in PD and revealed by a gravitational stimulus. Prompt recognition of sympathetic abnormalities might result in earlier therapeutic intervention, reduced orthostatic intolerance, and increased quality of life.
Hypertension 2007 Jan
PMID:Early abnormalities of vascular and cardiac autonomic control in Parkinson's disease without orthostatic hypotension. 1710 46


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