Gastrointestinal (GI) dysfunction is the most common non-motor symptom of Parkinson's disease (PD). Symptoms of GI dysmotility include early satiety and nausea from delayed gastric emptying, bloating from poor small bowel coordination, and constipation and defecatory dysfunction from impaired colonic transit. Understanding the pathophysiology and treatment of these symptoms in PD patients has been hampered by the lack of investigation into GI symptoms and pathology in PD animal models. We report that the prototypical parkinsonian neurotoxin, MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine), is a selective dopamine neuron toxin in the enteric nervous system (ENS). When examined 10 days after treatment, there was a 40% reduction of dopamine neurons in the ENS of C57Bl/6 mice administered MPTP (60 mg/kg). There were no differences in the density of cholinergic or nitric oxide neurons. Electrophysiological recording of neural-mediated muscle contraction in isolated colon from MPTP-treated animals confirmed a relaxation defect associated with dopaminergic degeneration. Behaviorally, MPTP induced a transient increase in colon motility, but no changes in gastric emptying or small intestine transit. These results provide the first comprehensive assessment of gastrointestinal pathophysiology in an animal model of PD. They provide insight into the impact of dopaminergic dysfunction on gastrointestinal motility and a benchmark for assessment of other PD model systems.

Elevated blood pressure (BP) variability has been linked to an increased risk of adverse cardiovascular events, but the biological factors which promote elevated BP variability are not entirely understood. We conducted a cross-sectional study to examine whether inflammatory factors might be associated with elevated BP variability during 24-hour ambulatory BP monitoring. Subjects were 140 healthy, normotensive adults. Inflammatory markers included C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α). Blood pressure variability was calculated as the within-subject standard deviation of BP values obtained during the daytime, nighttime, and 24-hour periods. In linear regression models that were adjusted for mean BP and other factors, CRP quartiles were positively associated with daytime systolic BP variability; for subjects in the lowest to highest CRP quartiles, the mean within-subject standard deviations of daytime systolic BP were 9.31, 9.62, 10.55, and 11.17, respectively (p for linear trend = .001). C-reactive protein showed similar positive associations with nighttime and 24-hour systolic BP variability. In contrast, TNF-α was not independently associated with systolic BP variability during any of the time periods. With respect to diastolic BP variability, we found significant positive associations between CRP and diastolic BP variability during all time periods, and between TNF-α and daytime diastolic BP variability. In conclusion, there are positive associations between markers of inflammation and BP variability in healthy, normotensive adults, suggesting that inflammation may be one of the factors that promotes increased BP variability.Keywords blood pressure; blood pressure monitoring; blood pressure variability; inflammation; C-reactive protein; tumor necrosis factor-alpha Elevated blood pressure (BP) variability during 24-hour ambulatory BP monitoring is associated with an increased risk of target organ damage, 1,2 early atherosclerosis, 3 and cardiovascular events. 3-5 The causes of increased BP variability, however, are not entirely understood. Inflammatory factors, by promoting vasoconstriction 6-10 and facilitating acute NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript blood pressure increases, 11 might play a role in increased BP variability. Yet data on the association between inflammatory markers and BP variability in humans are sparse. The present study examined whether two markers of inflammation, C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α), were positively associated with BP variability during 24-hour ambulatory BP monitoring in healthy men and women.The study design was cross-sectional. The study population was a sample of male and female subjects drawn from the Atlanta, Georgia metropolitan area. Subjects were eligible to participate in the study if they: (1) were 30 to 60 years of age; (2) had no history of hypertension and were not using antihypertensive medications; (3) had no history of cardiovascular disease (coronary disease...

No abstract

Our study suggests that after mitral valve surgery, there is significant improvement in New York Heart Association functional class and health status, especially in patients undergoing mitral valve repair.

No abstract