Cytoprotective effect of chlorogenic acid against α-synuclein-related toxicity in catecholaminergic PC12 cells

Parkinson's disease is a major neurodegenerative disease involving the selective degeneration of dopaminergic neurons and α-synuclein containing Lewy bodies formation in the substantia nigra. Although α-synuclein is a key molecule for both dopaminergic neuron death and the formation of inclusion bodies, the mechanism of α-synuclein induction of Parkinson's disease-related pathogenesis is not understood. In the present study, we found that the interaction between dopamine and α-synuclein requires the oxidation of dopamine. Furthermore, we examined the protective effect of chlorogenic acid, a major polyphenol contained in coffee, against α-syn and dopamine-related toxicity. Chlorogenic acid inhibits several DA/α-synuclein-related phenomenon, including the oxidation of dopamine, the interaction of oxidized dopamine with α-synuclein, and the oligomerization of α-synuclein under dopamine existing conditions in vitro. Finally, we showed that the cytoprotective effect against α-synuclein-related toxicity in PC12 cells that can be controlled by the Tet-Off system. Although the induction of α-synuclein in catecholaminergic PC12 cells causes a decrease in cell viability, chlorogenic acid rescued this cytotoxicity significantly in a dose dependent manner. These results suggest that the interaction of oxidized DA with α-synuclein may be a novel therapeutic target for Parkinson's disease, and polyphenols, including chlorogenic acid, are candidates as protective and preventive agents for Parkinson's disease onset.     

Psychological states and coping strategies after bereavement among spouses of cancer patients: a quantitative study in Japan

Purpose

The purposes of this study were (1) to characterize psychological states and coping strategies after bereavement among spouses of cancer patients in Japan and (2) to explore the factors associated with psychological states in oncology settings.

Methods

In March 2009, questionnaires to assess spouses’ psychological states, coping strategies, and mental health states (GHQ-28) were sent after patients died at the National Cancer Center of Japan. To address the first purpose, exploratory factor analysis, gender comparison, and calculation of correlation with age, time since bereavement, and mental health states were conducted. Hierarchical regression analysis was conducted to address the second purpose.

Results

A total of 821 spouses experiencing bereavement for 7?months to 7?years participated in the study. Psychological states revealed three factor structures: “Anxiety/Depression/Anger”, “Yearning”, and “Acceptance/Future-Oriented Feelings”. Coping strategies also revealed three factor structures: “Distraction”, “Continuing Bonds”, and “Social Sharing/Reconstruction”. Coping strategies represented 18?% to 34?% of each factor associated with psychological states, whereas the characteristics of bereaved spouses and deceased patients represented 6?% and less than 6?%, respectively. More “Distraction and Social Sharing/Reconstruction” and less “Continuing Bonds” were significantly associated coping strategies for achieving “Acceptance/Future-Oriented Feelings” (p?<?0.01).

Conclusions

Both psychological states and coping strategies after bereavement revealed three factor structures. Coping strategies was the primary, bereaved spouses’ characteristics was the secondary, and deceased patients’ characteristics was the tertiary factor associated with psychological states. Enhancing “Distraction” and “Social Sharing/Reconstruction”, and reducing “Continuing Bonds” might be promising strategies for achieving positive psychological states of the bereaved.     

The importance of pharmacokinetic consultation of cefepime treatment for <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> bacteremia: a case report of severe thermal burn injury

The patient is a 54-year-old man with severe thermal burn injury involving 45.5% of the total body-surface area, complicated with bacteremia caused by Pseudomonas aeruginosa with a cefepime MIC of 8 μg/ml. The plasma concentrations of cefepime 1 g every 6 h measured by validated high performance liquid chromatography were 25.8 μg/ml at 1 h and 6.28 μg/ml at 5 h after infusion, and 3.9 μg/ml before the infusion, when creatinine clearance was increased to 136 ml/min by vigorous fluid replacement. The pharmacokinetic–pharmacodynamic analyses in the one-compartment model with use of the Sawchuk–Zaske method revealed marked increase in the volume of distribution (28.9 l), total clearance (10.7 l/h), and shortening of plasma half- life (1.79 h) of cefepime, with time >MIC and 24-h area under the concentration–time-curve being 58% and 358, respectively. These pharmacokinetic parameters of cefepime quantified in the patient estimated a time >MIC of 87% if administered every 4 h. P. aeruginosa, however, was successfully eradicated without revision of the dosing regimen of cefepime. Decrease in creatinine clearance by correction of the fluid imbalance and wound closure by skin graft surgery likely contributed to the restoration of fluid shift, resulting in normal disposition of cefepime and favorable clinical outcome of the patient.