Subthalamic deep brain stimulation for the treatment of Parkinson disease

Background and purposeThe role of subthalamic nucleus deep brain stimulation (STN DBS) in the treatment of Parkinson disease (PD) is well established. The authors present a group of patients diagnosed with PD who were treated with STN DBS.Material and methodsBetween 2008 and 2009, 32 female and 34 male patients with PD were treated with STN DBS. Mean age at implantation was 57 ± 12 years. PD lasted from 6 to 21 years (mean 10 years). Patients were qualified for the surgery according to the CAPSIT-PD criteria. The STN was identified with direct and indirect methods. Macrostimulation and microrecording for STN identification were used in all cases. A unilateral STN DBS system was implanted in two cases and bilateral implantation was performed among rest of the group. Outcome was assessed six months after implantation.ResultsThe mean reduction of UPDRS III score among 51 patients who underwent follow-up was 45% (5-89%). Reduction of levodopa consumption varied from 15 to 100%. Infection forced the authors to remove the DBS system in one case four months after implantation. Skin erosion above the internal pulse generator was noted in four cases.ConclusionsCardinal symptoms of Parkinson's disease can be safely and effectively treated with STN DBS in selected group of patients.     

Sense of coherence mediates the relationship between the religious meaning system and coping styles in Polish older adults

Objectives: The links between religiousness and coping are complex, and previous research indicates that they may be mediated by coherence-related structures. The aim of this study was to examine whether sense of coherence (SOC) is a mediator in the relationships between the religious meaning system and coping styles in Polish older adults.

Method: In this study, 212 older adults (118 women and 94 men) participated. Their ages ranged from 65 to 79 years (M = 71.04; SD = 2.26). The group was a representative sample of Polish older adults in terms of social status, gender, and age. They completed three measures: the Religious Meaning System Questionnaire, the Sense of Coherence Scale (SOC-29), and the Coping Inventory for Stressful Situations.

Results: Findings showed that the religious meaning system had significant relationships with SOC and three coping styles: emotion-oriented coping, avoidance-oriented coping, and social diversion. In addition, SOC mediated the relations between the religious meaning system and three coping styles: the emotion-oriented, avoidance-oriented, and social diversion.

Conclusions: The positive associations between meaning-oriented religiousness, SOC, and coping styles imply that their underlying mechanisms are based on the structures of significance and comprehension. The character of mediational relations (i.e. mediator vs. suppressor) depended on the emotional and social coping strategies used by older adults.     

Redox properties of Met(35) in neurotoxic beta-amyloid peptide. A molecular modeling study

The beta-amyloid peptide (betaAP) is the principal component of plaque associated with the pathology of Alzheimer's disease. Part of its neurotoxicity appears to correlate with the ability of the peptide to reduce Cu(II) and form free radicals. Both processes are dependent on the presence and oxidizability of Met(35) in the C-terminus of the peptide but no mechanistic details on the reactions leading to Met oxidation are known. On the basis of previous studies with model peptides, we hypothesize that a one-electron oxidation of Met(35) in betaAP is facilitated through a neighboring group effect. Complexed to Cu(II) and/or in a lipid-mimicking environment, the solution structure of betaAP includes a large alpha-helical part. The solution NMR structure of betaAP1-40 in aqueous SDS micelles reveals an alpha-helix between residues 27 and 36, containing Met(35). In this helical C-terminus of betaAP, the peptide bond C=O group C-terminal of Ile(31) is located very close to the Met(35) sulfur and could stabilize a Met(35) sulfide radical cation through formation of an (S-O) three-electron bond. In the present paper, we have computationally validated this hypothesis using Langevin dynamics methods to determine the collision frequency of the Met(35) thioether sulfur and the oxygen atoms of several peptide bonds in the betaAP sequence. Nanosecond time scale computations were carried out for four distinct betaAP congeners, betaAP26-40, betaAP26-36, betaAP26-40(Ile(31)Pro), betaAP40-26, and their respective Met(35)-sulfur-centered cation radicals. Here, betaAP26-40, betaAP26-40(Ile(31)Pro) and betaAP40-26 are representative fragments of the full length betaAP1-42 or betaAP42-1 sequence, respectively, whereas betaAP26-36 represents a unique betaAP sequence for which biological data are available. Initial structures of betaAP26-40, betaAP26-40(Ile(31)Pro), and betaAP26-36 were selected to be identical to that of the betaAP26-40 or betaAP26-36 sequence in full-length betaAP1-40. As the structures of betaAP40-26 and betaAP42-1 are not known, various initial conformations such as alpha-helix and antiparallel beta-sheet were selected for betaAP40-26. Our computational results show that betaAP26-40, representative for the same sequence in full-length betaAP1-42, has the highest tendency to form (S-O) bonds between Ile(31)C=O and Met(35)S. We conclude that native betaAP1-42 has a higher tendency to support Met(35) oxidation through (S-O) bond formation, consistent with the experimental observation that betaAP1-42 is more neurotoxic compared to the other investigated sequences.     

An attempt at evaluating borderline conditions of Parkinson's disease and its preclinical stage on the basis of clinical and morphological correlation

The aim of the investigations was to find to what extent neurodegenerative changes develop in the brains of patients with no clinical symptoms of dementia, parkinsonism and other neurodegenerative diseases. It has been found that neurodegenerative pathology, as evaluated using immunohistochemical methods with monoclonal antibodies (Mab) against ubiquitin, tau protein, alpha-synuclein, and beta-amyloid, occurs more frequently than the presence of Lewy bodies. The degenerative changes involved the neurones of cerebral and cerebellar cortex, basal ganglia and medulla oblongata, where neurofibrillary tangles were found. Mab positive materials have been found in the cytoplasm of the cell body and the cell processes (axons) of the neurones and glial cells. Senile plaques, beta-amyloid positive, were frequently noted.