Risk of Parkinson Disease Among Service Members at Marine Corps Base Camp Lejeune.

Importance: An increased risk of Parkinson disease (PD) has been associated with exposure to the solvent trichloroethylene (TCE), but data are limited. Millions of people in the US and worldwide are exposed to TCE in air, food, and water. Objective: To test whether the risk of PD is higher in veterans who served at Marine Corps Base Camp Lejeune, whose water supply was contaminated with TCE and other volatile organic compounds (VOCs), compared with veterans who did not serve on that base. Design, Setting, and Participants: This population-based cohort study examined the risk for PD among all Marines and Navy personnel who resided at Camp Lejeune, North Carolina (contaminated water) (n = 172 128), or Camp Pendleton, California (uncontaminated water) (n = 168 361), for at least 3 months between 1975 and 1985, with follow-up from January 1, 1997, until February 17, 2021. Veterans Health Administration and Medicare databases were searched for International Classification of Diseases diagnostic codes for PD or other forms of parkinsonism and related medications and for diagnostic codes indicative of prodromal disease. Parkinson disease diagnoses were confirmed by medical record review. Exposures: Water supplies at Camp Lejeune were contaminated with several VOCs. Levels were highest for TCE, with monthly median values greater than 70-fold the permissible amount. Main Outcome and Measures: Risk of PD in former residents of Camp Lejeune relative to residents of Camp Pendleton. In those without PD or another form of parkinsonism, the risk of being diagnosed with features of prodromal PD were assessed individually and cumulatively using likelihood ratio tests. Results: Health data were available for 158 122 veterans (46.4%). Demographic characteristics were similar between Camp Lejeune (5.3% women, 94.7% men; mean [SD] attained age of 59.64 [4.43] years; 29.7% Black, 6.0% Hispanic, 67.6% White; and 2.7% other race and ethnicity) and Camp Pendleton (3.8% women, 96.2% men; mean [SD] age, 59.80 [4.62] years; 23.4% Black, 9.4% Hispanic, 71.1% White, and 5.5% other race and ethnicity). A total of 430 veterans had PD, with 279 from Camp Lejeune (prevalence, 0.33%) and 151 from Camp Pendleton (prevalence, 0.21%). In multivariable models, Camp Lejeune veterans had a 70% higher risk of PD (odds ratio, 1.70; 95% CI, 1.39-2.07; P < .001). No excess risk was found for other forms of neurodegenerative parkinsonism. Camp Lejeune veterans also had a significantly increased risk of prodromal PD diagnoses, including tremor, anxiety, and erectile dysfunction, and higher cumulative prodromal risk scores. Conclusions and Relevance: The study's findings suggest that the risk of PD is higher in persons exposed to TCE and other VOCs in water 4 decades ago. Millions worldwide have been and continue to be exposed to this ubiquitous environmental contaminant.

Induction and Assessment of Levodopa-induced Dyskinesias in a Rat Model of Parkinson's Disease.

Levodopa (L-DOPA) remains the gold-standard therapy used to treat Parkinson's disease (PD) motor symptoms. However, unwanted involuntary movements known as L-DOPA-induced dyskinesias (LIDs) develop with prolonged use of this dopamine precursor. It is estimated that the incidence of LIDs escalates to approximately 90% of individuals with PD within 10-15 years of treatment. Understanding the mechanisms of this malady and developing both novel and effective anti-dyskinesia treatments requires consistent and accurate modeling for pre-clinical testing of therapeutic interventions. A detailed method for reliable induction and comprehensive rating of LIDs following 6-OHDA-induced nigral lesioning in a rat model of PD is presented here. Dependable LID assessment in rats provides a powerful tool that can be readily utilized across laboratories to test emerging therapies focused on reducing or eliminating this common treatment-induced burden for individuals with PD.

Chitosan coated synergistically engineered nanoemulsion of Ropinirole and nigella oil in the management of Parkinson's disease: Formulation perspective and In vitro and In vivo assessment.

The research presented aims at developing Ropinirole hydrochloride (RHCl) nanoemulsion (NE) with nigella oil for Parkinson's disease (PD). In silico study was done to explore interactions of ropinirole and thymoquinone at receptor site (TNF-α and NFK-ß). Ropinirole and Thymoquinone forms a hydrogen bond with residue Arginine 201 and residue Arginine 253 with a bond length of 1.89 Å and 2.30 Å at the NF-κß receptor. NE was optimized using Central Composite Rotatable Design (CCRD). The globule size of chitosan coated NE, Polydispersity index (PDI) and zeta potential were 183.7 ± 5.2 nm, 0.263 ± 0.005, and 24.9 mV respectively. NE exhibited 85.28% transmittance showing the formulation was clear and transparent. TEM showed that NE had spherical globules with no aggregation. The formulation had a stable pH value of 5.8 ± 0.18. In vitro release and permeation studies exhibited 2 folds and 3.4 folds enhancement when compared with the drug suspension. Neurobehavioral activity and biochemical parameters corroborated well with the pharmacokinetic results. Histopathological study and immunohistochemical analysis were performed to get better picture of 6-OHDA induced toxicity and reversal of PD symptoms. Thus, the NE tailored is a promising synergistic approach yielding enticing outcomes for better management of PD related symptoms.

Long-term effects of PM2·5 on neurological disorders in the American Medicare population: a longitudinal cohort study.

BACKGROUND: Accumulating evidence links fine particulate matter (PM2·5) to premature mortality, cardiovascular disease, and respiratory disease. However, less is known about the influence of PM2·5 on neurological disorders. We aimed to investigate the effect of long-term PM2·5 exposure on development of Parkinson's disease or Alzheimer's disease and related dementias. METHODS: We did a longitudinal cohort study in which we constructed a population-based nationwide open cohort including all fee-for-service Medicare beneficiaries (aged ≥65 years) in the contiguous United States (2000-16) with no exclusions. We assigned PM2·5 postal code (ie, ZIP code) concentrations based on mean annual predictions from a high-resolution model. To accommodate our very large dataset, we applied Cox-equivalent Poisson models with parallel computing to estimate hazard ratios (HRs) for first hospital admission for Parkinson's disease or Alzheimer's disease and related dementias, adjusting for potential confounders in the health models. FINDINGS: Between Jan 1, 2000, and Dec 31, 2016, of 63 038 019 individuals who were aged 65 years or older during the study period, we identified 1·0 million cases of Parkinson's disease and 3·4 million cases of Alzheimer's disease and related dementias based on primary and secondary diagnosis billing codes. For each 5 µg/m3 increase in annual PM2·5 concentrations, the HR was 1·13 (95% CI 1·12-1·14) for first hospital admission for Parkinson's disease and 1·13 (1·12-1·14) for first hospital admission for Alzheimer's disease and related dementias. For both outcomes, there was strong evidence of linearity at PM2·5 concentrations less than 16 µg/m3 (95th percentile of the PM2·5 distribution), followed by a plateaued association with increasingly larger confidence bands. INTERPRETATION: We provide evidence that exposure to annual mean PM2·5 in the USA is significantly associated with an increased hazard of first hospital admission with Parkinson's disease and Alzheimer's disease and related dementias. For the ageing American population, improving air quality to reduce PM2·5 concentrations to less than current national standards could yield substantial health benefits by reducing the burden of neurological disorders. FUNDING: The Health Effects Institute, The National Institute of Environmental Health Sciences, The National Institute on Aging, and the HERCULES Center.

Risk factors of Parkinson disease: Simultaneous assessment, interactions, and etiologic subtypes.

OBJECTIVE: To perform a simultaneous evaluation of potential risk/protective factors of Parkinson disease (PD) to identify independent risk/protective factors, to assess interaction among factors, and to determine whether identified risk factors predict etiologic subtypes of PD. METHODS: We designed a large case-control study assessing 31 protective/risk factors of PD, including environmental and lifestyle factors, comorbid conditions, and drugs. The study enrolled 694 patients with PD and 640 healthy controls from 6 neurologic centers. Data were analyzed by logistic regression models, additive interaction models, and cluster analysis. RESULTS: The simultaneous assessment of 31 putative risk/protective factors of PD showed that only coffee consumption (odds ratio [OR] 0.6; 95% confidence interval [CI] 0.4-0.9), smoking (OR 0.7, 95% CI 0.6-0.9), physical activity (OR 0.8, 95% CI 0.7-0.9), family history of PD (OR 3.2, 95% CI 2.2-4.8), dyspepsia (OR 1.8, 95% CI 1.3-2.4), and exposure to pesticides (OR 2.3, 95% CI1.3-4.2), oils (OR 5.6, 95% CI 2.3-13.7), metals (OR 2.8, 95% CI 1.5-5.4), and general anesthesia (OR 6.1, 95% CI 2.9-12.7) were independently associated with PD. There was no evidence of interaction among risk/protective factors, but cluster analysis identified 4 subtypes with different risk factor profiles. In group 1, all patients had a family history of PD, while dyspepsia or exposure to toxic agents was present in 30% of patients. In groups 2 and 3, a family history of PD was lacking, while exposure to toxic agents (group 2) and dyspepsia (group 3) played major roles. Group 4 consisted of patients with no risk factors. CONCLUSIONS: This study demonstrated that 9 factors independently modify PD risk by coexisting in the same patient rather than interacting with others. Our study suggests the need for future preventive strategies aimed at reducing the coexistence of different risk factors within the same participant.

Neurotoxin-Induced Animal Models of Parkinson Disease: Pathogenic Mechanism and Assessment.

Parkinson disease (PD) is the second most common neurodegenerative movement disorder. Pharmacological animal models are invaluable tools to study the pathological mechanisms of PD. Currently, invertebrate and vertebrate animal models have been developed by using several main neurotoxins, such as 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, paraquat, and rotenone. These models achieve to some extent to reproduce the key features of PD, including motor defects, progressive loss of dopaminergic neurons in substantia nigra pars compacta, and the formation of Lewy bodies. In this review, we will highlight the pathogenic mechanisms of those neurotoxins and summarize different neurotoxic animal models with the hope to help researchers choose among them accurately and to promote the development of modeling PD.

PBPK/PD assessment for Parkinson's disease risk posed by airborne pesticide paraquat exposure.

Exposure to several specific pesticides has led to an increase of Parkinson's disease (PD) risk. However, it is difficult to quantify the PD population risk related to certain pesticides in regions where environmental exposure data are scarce. Furthermore, the time trend of the prevalence and incidence of PD embedded in the background relationship between PD risk and pesticide exposures has not been well characterized. It has been convincingly identified that a key pesticide associated significantly with an increased risk trend of PD is paraquat (PQ). Here, we present a novel, probabilistic population-based exposure-response approach to quantify the contribution from PQ exposure to prevalence risk of PD. We found that the largest PQ exposure contributions occurred in its positive trend during 2004-2011, with the PQ contributing nearly 21 and 24%, respectively, to the PD prevalence rates among the age groups of 70-79 and ≥ 80 years in Taiwan. We also employed the present population risk model to predict the PQ-induced PD prevalence based on the projected rates of increase in PQ exposure associated with age-specific population. The predicted outcome can be used as an early warning signal for public health authorities. We suggest that a mechanistic understanding of the contribution of a specific pesticide exposure to PD risk trends is crucial to enhance our insights into the perspective on the impacts of environmental exposure on the neurodegenerative diseases.

Trichloroethylene and Parkinson's Disease: Risk Assessment.

This study was conducted to investigate the mechanism of action and extent of selective dopaminergic neurodegeneration caused by exposure to trichloroethylene (TCE) leading to the endogenous formation of the neurotoxin 1-trichloromethyl-1,2,3,4-tetrahydro-ß-carboline (TaClo) in rodents. Beginning at 3 months of age, male C57BL/6 mice received oral TCE dissolved in vehicle for 8 months. Dopaminergic neuronal loss was assessed by nigral tyrosine hydroxylase (TH) immunoreactivity. Selective dopaminergic neurodegeneration was determined based on histological analysis of non-dopaminergic neurons in the brain. Behavioral assays were evaluated using open field activity and rotarod tests. Mitochondrial complex I activity, oxidative stress markers, and microglial activation were also examined in the substantia nigra. The level of TaClo was detected using HPLC-electrospray ionization tandem mass spectrometry. Dopaminergic neurotoxicity of TaClo was determined in midbrain organotypic cultures from rat pups. Following 8 months of TCE treatment, there was a progressive and selective loss of 50% of the dopaminergic neurons in mouse substantia nigra (SN) and about 50% loss of dopamine and 72% loss of 3,4-dihydroxyphenylacetic acid in the striatum, respectively. In addition, motor deficits, mitochondrial impairment, oxidative stress, and inflammation were measured. TaClo content was quantified in the brain after TCE treatment. In organotypic cultures, TaClo rather than TCE induced dopaminergic neuronal loss, similar to MPP+. TCE exposure may stimulate the endogenous formation of TaClo, which is responsible for dopaminergic neurodegeneration. However, even prolonged administration of TCE was insufficient for producing a greater than 50% loss of nigral dopamine neurons, indicating that additional co-morbid factors would be needed for mimicking the profound loss of dopamine neurons seen in Parkinson's disease.

Diseases Associated With Exposure to Contaminants in the Water Supply at Camp Lejeune. Final rule.

The Department of Veterans Affairs (VA) amends its adjudication regulations regarding presumptive service connection, adding certain diseases associated with contaminants present in the base water supply at U.S. Marine Corps Base Camp Lejeune (Camp Lejeune), North Carolina, from August 1, 1953, to December 31, 1987. This final rule establishes that veterans, former reservists, and former National Guard members, who served at Camp Lejeune for no less than 30 days (consecutive or nonconsecutive) during this period, and who have been diagnosed with any of eight associated diseases, are presumed to have incurred or aggravated the disease in service for purposes of entitlement to VA benefits. In addition, this final rule establishes a presumption that these individuals were disabled during the relevant period of service for purposes of establishing active military service for benefits purposes. Under this presumption, affected former reservists and National Guard members have veteran status for purposes of entitlement to some VA benefits. This amendment implements a decision by the Secretary of Veterans Affairs that service connection on a presumptive basis is warranted for claimants who served at Camp Lejeune during the relevant period and for the requisite amount of time and later develop certain diseases.

Survival and Functional Outcomes after Hip Fracture among Nursing Home Residents.

Following the implementation of a long-term care insurance system for the elderly in Korea, many nursing homes have been established and many more patients than ever before have been living at nursing homes. Despite the fact that this is a high-risk group vulnerable to hip fractures, no study has yet been conducted in Korea on hip fracture incidence rates and prognoses among patients residing at nursing homes. We recently studied 46 cases of hip fracture in nursing homes; more specifically, we investigated the most common conditions under which fractures occur, and examined the degree of recovery of ambulatory ability and the mortality within 1 yr. Among those who had survived after 1 yr, the number of non-functional ambulators increased from 8 hips before hip fracture to 19 hips at final post-fracture follow-up. These individuals showed poor recovery of ambulatory ability, and the number who died within one year was 11 (23.9%), a rate not significantly different from that among community-dwelling individuals. It was evident that hip-joint-fracture nursing home residents survived for similar periods of time as did those dwelling in the community, though under much more uncomfortable conditions. The main highlight of this report is that it is the first from Korea on nursing home residents' ambulatory recovery and one-year mortality after hip fracture. The authors believe that, beginning with the present study, the government should collect and evaluate the number of hips fractured at nursing facilities in order to formulate criteria that will help to enable all patients to select safer and better-quality nursing facilities for themselves or their family members.

Parkinson's disease and pesticide exposure--a new assessment.

Parkinson's disease (PD) is an idiopathic disease and its pathological feature is a loss of pigmented neurons in the substantia nigra. Some commonly used pesticides possess neurotoxicity, and exposure to such compounds may trigger mechanisms similar to those in the development of idiopathic PD. We conducted a systematic review of epidemiological studies, aiming at a critical evaluation of the association between the development of PD and pesticide exposure. Reported effect sizes (ES) in the relevant studies were pooled into the meta-analysis to derive summary ES. The summary ES suggested a significantly positive association between PD and overall pesticide use (non-occupational and/or occupational pesticide use) [1.42; 95% confidence interval (CI) 1.32 to 1.52, the fixed-effects model], as well as between PD and occupational pesticide exposure (1.49 with a 95% CI of 1.34-1.66). Both occupational herbicide and occupational insecticide exposure showed a significant association with PD. The results of the meta-analysis reported in this study suggest the existence of a statistically positive association between PD and pesticide exposure. The majority of the studies that were pooled in the meta-analysis were case-control design with very few cohort studies and most with poor exposure characterization thus, any further case-control studies using similar methodologies are unlikely to have a significant impact or understanding on the currently-reported association between pesticide exposure and the development of idiopathic PD. Therefore, we believe that if further epidemiological studies are going to be conducted in the area, they should be prospective cohort studies that will include accurate exposure assessment.

Obstacles to the development of a neuroprotective therapy for Parkinson's disease.

A neuroprotective or disease-modifying therapy that can slow or stop disease progression and prevent the development of intolerable disability is the major unmet medical need in the treatment of Parkinson's disease (PD). Many putative neuroprotective agents have been identified in the laboratory, but none has been unequivocally demonstrated to provide disease-modifying effects in PD patients, even when clinical trials are positive. Obstacles to defining a neuroprotective therapy in PD include: (1) uncertainty about the cause of PD and precisely what to target, (2) a reliable animal model in which to test putative neuroprotective agents that accurately predicts results in PD patients, (3) insight about which dose to employ in clinical trials and which patient group to study, (4) a clinical trial design that reliably differentiates disease-modifying and symptomatic effects and that is acceptable to regulatory authorities, and (5) the cost and time of the development program. Advances have been made in each of these areas, thereby increasing the prospects of developing a neuroprotective or disease-modifying therapy in the not-too-distant future. These issues are reviewed in the present article.

Assessment of the role of multidrug resistance-associated proteins in MPTP neurotoxicity in mice.

GOALS: The available scientific data indicate that the pathomechanism of Parkinson's disease (PD) involves the accumulation of endogenous and exogenous toxic substances. The disruption of the proper functioning of certain transporters in the blood-brain barrier and in the blood-cerebrospinal fluid barrier in PD would accompany to that accumulation. Although there is an emerging role of the dysfunction of multidrug resistance-associated proteins (MRPs), members of ATP-b nding cassette (ABC) transporter superfamily, in neurodegenerative disorders, there is only a few available data as regards PD. So the aim of our study was the assessment of the role of certain MRPs (1 ,2, 4 and 5) in neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine METHODS: Following the intraperitoneal administration of silymarin (with MRP1, 2, 4 and 5 inhibitory effects), naringenin (with MRP1, 2 and 4 stimulatory effects), sulfinpyrazone (with MRP1, 4 and 5 inhibitory and MRP2 stimulatory effects) and allopurinol (with MRP4 stimulatory effect in doses of 100 mg/kg, 100 mg/kg, 100 mg/kg and 60 mg/kg, respectively, for one week before and after the administration of MPTP in C57B/6 mice in acute dosing regimen the striatal concentrations of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid has been measured using high-performance liquid chromatography. RESULTS: Although the results of these experiments showed that neither of these substances exerted significant influence on MPTP-induced striatal depletion of dopamine and its metabolites, naringenin exerted a slight prevention of dopamine decrease, while allopurinol considerably enhanced the MPTP-induced lethality in mice. The explanation of these findings would be that the stimulation of MRP1- and MRP2-mediated transport of glutathione conjugates of toxic substances may have slight beneficial effects, while stimulation of MRP4-mediated efflux of brain urate, which has an important antioxidant potency, may worsen the effects of oxidative stress.

Retrospective assessment of occupational exposure to whole-body vibration for a case-control study.

Occupational whole-body vibration is often studied as a risk factor for conditions that may arise soon after exposure, but only rarely have studies examined associations with conditions arising long after occupational exposure has ceased. We aimed to develop a method of constructing previous occupational whole-body vibration exposure metrics from self-reported data collected for a case-control study of Parkinson's disease. A detailed job history and exposure interview was administered to 808 residents of British Columbia, Canada (403 people with Parkinson's disease and 405 healthy controls). Participants were prompted to report exposure to whole-body vibrating equipment. We limited the data to exposure reports deemed to be above background exposures and used the whole-body vibration literature (typically reporting on seated vector sum measurements) to assign intensity (acceleration) values to each type of equipment reported. We created four metrics of exposure (duration of exposure, most intense equipment exposure, and two dose metrics combining duration and intensity) and examined their distributions and correlations. We tested the role of age and gender in predicting whole-body vibration exposure. Thirty-six percent of participants had at least one previous occupational exposure to whole-body vibrating equipment. Because less than half of participants reported exposure, all continuous metrics exhibited positively skewed distributions, although the distribution of most intense equipment exposure was more symmetrically distributed among the exposed. The arithmetic mean of duration of exposure among those exposed was 14.0 (standard deviation, SD: 14.2) work years, while the geometric mean was 6.8 (geometric SD, GSD: 4.5). The intensity of the most intense equipment exposure (among the exposed) had an arithmetic mean of 0.9 (SD: 0.3) m·s(-2) and a geometric mean of 0.8 (GSD: 1.4). Male gender and older age were both associated with exposure, although the effect of age was attenuated after adjustment for gender. The methods developed allowed us to create continuous metrics of whole-body vibration retrospectively, displaying useful variance for epidemiologic studies.

Geographic and ethnic variation in Parkinson disease: a population-based study of US Medicare beneficiaries.

BACKGROUND: Parkinson disease is a common neurodegenerative disease. The racial, sex, age, and geographic distributions of Parkinson disease in the US are unknown. METHODS: We performed a serial cross-sectional study of US Medicare beneficiaries aged 65 and older from the years 1995, and 2000-2005. Using over 450,000 Parkinson disease cases per year, we calculated Parkinson disease prevalence and annual incidence by race, age, sex, and county. Spatial analysis investigated the geographic distribution of Parkinson disease. RESULTS: Age-standardized Parkinson disease prevalence (per 100,000) was 2,168.18 (+/-95.64) in White men, but 1,036.41 (+/-86.01) in Blacks, and 1,138.56 (+/-46.47) in Asians. The incidence ratio in Blacks as compared to Whites (0.74; 95% CI = 0.732-0.748) was higher than the prevalence ratio (0.58; 95% CI = 0.575-0.581), whereas the incidence ratio for Asians (0.69; 95% CI = 0.657-0.723) was similar to the prevalence ratio (0.62; 95% CI = 0.617-0.631). Bayesian mapping of Parkinson disease revealed a concentration in the Midwest and Northeast regions. Mean county incidence by quartile ranged from 279 to 3,111, and prevalence from 1,175 to 13,800 (per 100,000). Prevalence and incidence in urban counties were greater than in rural ones (p < 0.01). Cluster analysis supported a nonrandom distribution of both incident and prevalent Parkinson disease cases (p < 0.001). CONCLUSIONS: Parkinson disease is substantially more common in Whites, and is nonrandomly distributed in the Midwest and Northeastern US.

Spatial distribution of Parkinson's disease mortality in Spain, 1989-1998, as a guide for focused aetiological research or health-care intervention.

BACKGROUND: Aetiologically, genetic and environmental factors having an uneven spatial distribution may underlie Parkinson's disease (PD). Undiagnosis of PD in selected regions might have limited access to treatment with levodopa and simultaneously, if present at death, determined PD underreporting at the death record. The purpose of this study was to describe and analyse municipal mortality due to PD in Spain in aetiological and interventional perspective. METHODS: PD mortality at a municipal level was modelled using the Besag-York- Molliè autoregressive spatial model, combining demographic information with cause-of-death diagnostic data (International Classification of Diseases 9th Revision (ICD-9) code 332.0). Municipal relative risks (RRs) were independently estimated for women, men and both sexes, and plotted on maps depicting smoothed RR estimates and the distribution of the posterior probability of RR>1. RESULTS: A south-north gradient, with large geographical areas suggesting clustered towns with high mortality, was seen in Asturias, the Basque Country, Balearic Islands and, particularly, in the Lower Ebro valley around Tarragona. Similarly, there was a suggestion that lowest mortality was clustered in the south-east and south-west. We identified some isolated or clustered municipalities with high mortality that were situated near industrial plants reported to be associated with environmental xenobiotic emissions. However, the same pattern was also observed for some cities with low mortality. CONCLUSION: Municipal PD mortality in Spain was unevenly distributed. Patterns were roughly similar to reported provincial PD mortality and use of levodopa. While the overall pattern appears to result from spatially selective PD undiagnosis, and can not be ascribed to industrial emissions, it can not be excluded that selected "hot spots" reflect genetic factors and/or environmental exposures inducing parkinsonism. A few municipal populations, located in low-mortality-risk areas in the vicinity of polluting plants or registering high excess PD mortality, might constitute a priority for conducting direct etiological studies. Additionally, interventions aimed to reduce potential PD undiagnosis might be most appropriate in the South.

Assessment of symptomatic and neuroprotective efficacy of Mucuna pruriens seed extract in rodent model of Parkinson's disease.

Mucuna pruriens (MP) has long been used in Indian traditional medicine as support in the treatment of Parkinson's disease. However, no systematic preclinical studies that aimed at evaluating the efficacy of this substance are available to date. This study undertook an extensive evaluation of the antiparkinsonian effects of an extract of MP seeds known to contain, among other components, 12.5% L: -dihydroxyphenylalanine (L: -DOPA), as compared to equivalent doses of L: -DOPA. Moreover, the neuroprotective efficacy of MP and its potential rewarding effects were evaluated. The results obtained reveal how an acute administration of MP extract at a dose of 16 mg/kg (containing 2 mg/kg of L: -DOPA) consistently antagonized the deficit in latency of step initiation and adjusting step induced by a unilateral 6-hydroxydopamine lesion, whereas L: -DOPA was equally effective only at the doses of 6 mg/kg. At the same dosage, MP significantly improved the placement of the forelimb in vibrissae-evoked forelimb placing, suggesting a significant antagonistic activity on both motor and sensory-motor deficits. The effects of MP extract were moreover investigated by means of the turning behavior test and in the induction of abnormal involuntary movements (AIMs) after either acute or subchronic administration. MP extract acutely induced a significantly higher contralateral turning behavior than L: -DOPA (6 mg/kg) when administered at a dose of 48 mg/kg containing 6 mg/kg of L: -DOPA. On subchronic administration, both MP extract (48 mg/kg) and L: -DOPA (6 mg/kg) induced sensitization of contralateral turning behavior; however, L: -DOPA alone induced a concomitant sensitization in AIMs suggesting that the dyskinetic potential of MP is lower than that of L: -DOPA. MP (48 mg/kg) was also effective in antagonizing tremulous jaw movements induced by tacrine, a validated test reproducing parkinsonian tremor. Furthermore, MP induced no compartment preference in the place preference test, indicating the lack of components characterized by rewarding effects in the extract. Finally, in a subchronic mice model of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine hydrochloride (MPTP)-induced dopamine neuron degeneration, MP extract did not prove capable of preventing either tyrosine hydroxylase decrease induced by MPTP or astroglial or microglial activation as assessed by means of GFAP and CD11b immunohistochemistry, supporting the absence of neuroprotective effects by MP. Characterization MP extract strongly supports its antiparkinsonian activity.

The incidence and risk factors associated with postoperative delirium in geriatric patients undergoing surgery for suspected gynecologic malignancies.

BACKGROUND: The incidence of postoperative delirium (PD) in the elderly ranges between 3-60% but has never been examined in gynecologic oncology. Our goal was to identify pre, intra, and postoperative risk factors associated with the development of PD. METHODS: English speaking women of 60 years and above undergoing major surgery for suspected gynecologic malignancies were invited to participate. Enrolled patients were administered a pre and postoperative Mini-Mental State Exam (MMSE), and the postoperative Confusion Assessment Method was used to diagnosis PD. Pre, intra, and postoperative clinicopathology parameters were collected. Statistics included the Pearson chi-squared tests and multivariate logistic regression. RESULTS: Eighteen of a total of 103 patients (17.5%) developed PD. Univariate analysis revealed significant associations (p<0.05) between the development of delirium and age, albumin level, Charlson comorbidity index, performance status, dementia, level of education, number of pre and postoperative medications, prolonged oxygen or Foley catheter usage (>2 d), increased narcotic use (above standard regimens), postoperative transfusion, bed restriction and change in MMSE scores (pre vs. post). Using multivariate logistic regression analysis, older patients (p=0.0002), on multiple medications (p=0.008), given additional narcotic doses (p<0.0001) were at highest risk for the development of delirium. Intraoperative parameters were not correlated with outcome. CONCLUSIONS: PD is a common complication in older women undergoing major gynecologic surgery. Increased narcotics, age, and preoperative medications were strongly associated with this adverse event. Prevention needs to focus on i) identifying patients at higher risk for PD based on preoperative parameters, and ii) eliminating known postoperative risk factors.

On the use of low-cost computer peripherals for the assessment of motor dysfunction in Parkinson's disease--quantification of bradykinesia using target tracking tasks.

The potential of computer games peripherals to measure the motor dysfunction in Parkinson's diseases is assessed. Of particular interest is the quantification of bradykinesia. Previous studies used modified or custom haptic interfaces, here an unmodified force feedback joystick and steering wheel are used with a laptop. During testing an on screen cursor moves in response to movements of the peripheral, the user has to track a continuously moving target (pursuit tracking), or move to a predetermined target (step tracking). All tasks use movement in the horizontal axis, allowing use of joystick or steering wheel. Two pursuit tracking tasks are evaluated, pseudo random movement, and a swept frequency task. Two step tracking tasks are evaluated, movement between two or between two of five fixed targets. Thirteen patients and five controls took part on a weekly basis. Patients were assessed for bradykinesia at each session using standard clinical measures. A range of quantitative measures was developed to allow comparison between and within patients and controls using analysis of variance (ANOVA). Both peripherals are capable of discriminating between controls and patients, and between patients with different levels of bradykinesia. Recommendations for test procedures and peripherals are given.