Peripheral expression of key regulatory kinases in Alzheimer's disease and Parkinson's disease.

Alteration of key regulatory kinases may cause aberrant protein phosphorylation and aggregation in Alzheimer's disease (AD) and Parkinson's disease (PD). In this study, we investigated expression and phosphorylation status of glycogen synthase kinase 3 (GSK-3), protein kinase B (Akt) and tau protein in peripheral blood lymphocytes of 20 AD, 25 PD patients and 20 healthy controls. GSK-3 was increased in AD and PD patients. In these latter, GSK-3 levels were positively correlated with daily L-Dopa intake. Phosphorylated Akt expression was augmented in both groups; total Akt levels were increased only in AD patients and were positively correlated with disease duration and severity. Total and phosphorylated tau were increased only in AD, with phospho-tau levels being positively correlated with levels of total tau, Akt, and disease duration. No correlations between protein levels and clinical variables were found in PD patients. Investigation of peripheral changes in the expression of specific kinases may, therefore, lead to the development of innovative biomarkers of neurodegeneration, particularly for AD.

Functional and neurochemical changes of the gastrointestinal tract in a rodent model of Parkinson's disease.

Patients with Parkinson's disease develop motor disturbances often accompanied by peripheral autonomic dysfunctions, including gastrointestinal disorders, such as dysphagia, gastric stasis and constipation. While the mechanisms subserving enteric autonomic dysfunctions are not clearly understood, they may involve the enteric dopaminergic and/or nitrergic systems. In the present study, we demonstrate that rats with unilateral 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons develop a marked inhibition of propulsive activity compared to sham-operated controls, as indicated by a 60% reduction of daily fecal output at the 4th week of observation. Immunohistochemical data revealed that 6-hydroxydopamine treatment did not affect the total number of HuC/D-positive myenteric neurons in both the proximal and distal segments of ileum and colon. Conversely, in the distal ileum and proximal colon the number of nitrergic neurons was significantly reduced. These results suggest that a disturbed distal gut transit, reminiscent of constipation in the clinical setting, may occur as a consequence of a reduced propulsive motility, likely due to an impairment of a nitric oxide-mediated descending inhibition during peristalsis.

Peripheral proteasome and caspase activity in Parkinson disease and Alzheimer disease.

BACKGROUND: Defects of the ubiquitin-proteasome (UP) system, a multicatalytic complex degrading polyubiquitinated proteins, may intervene in the pathogenesis of neurodegenerative disorders characterized by intracellular formation of protein aggregates such as Parkinson disease (PD) and Alzheimer disease (AD) by inducing proapoptotic conditions. METHODS: The authors measured the activity of proteolytic UP core, proteasome 20S, and of proapoptotic caspase-3 and -9 in peripheral blood lymphocytes (PBLs) of PD and AD patients to establish whether changes in these systems are detectable peripherally. RESULTS: Proteasome 20S activity was reduced in PBLs of treated PD patients vs healthy controls (mean +/- SEM: 1.0 +/- 0.1 vs 2.3 +/- 0.2 nmol 7-amino-4-methylcoumarin (AMC)/10(6) cells, p < 0.001), whereas marked increases in caspase-3 activity (1370 +/- 153 vs 586 +/- 104 pmol AMC/10(6) cells, p < 0.001) and caspase-9 activity (873 +/- 86 vs 304 +/- 27 U/10(6) cells, p < 0.001) were found. Increased caspase-9 activity was also detected in PBLs of untreated PD patients (900 +/- 193 U/10(6) cells). PD duration and severity (Unified Parkinson's Disease Rating Scale score) were inversely correlated with proteasome 20S activity and directly correlated with caspase-3 activity. An inverse correlation was also observed in PD patients between caspase-3 activity and proteasome 20S activity. No significant changes in proteasome 20S or caspase activity or correlations between biochemical and clinical variables were found in patients with AD. CONCLUSIONS: A decrease in proteasome activity, possibly related to caspase activation, is detectable in peripheral blood lymphocytes of patients with Parkinson disease but not patients with Alzheimer disease, suggesting that these variables may be considered for the development of peripheral biomarkers of Parkinson disease.

[Ultrasonography assessment of ossification foci of the wrist and pubertal growth spurt]. / Valutazione ecografica dei nuclei di ossificazione del polso e del picco di crescita puberale.

High-resolution ultrasound (US) of the hand and wrist was compared with radiography in 26 young patients (mean age: 11.4 years) to be submitted to orthodontic therapy. US scans were targeted on the ossification centers critical for the growth spurt, namely the pisiform and adductor sesamoid bones of the metacarpophalangeal joint of the thumb and the cartilage of the distal phalanx of the third finger. All images were retrospectively reviewed on a double-blind basis by two independent observers who gave a conspicuity score to each structure of interest. All the scores were submitted to statistical analysis with the Wilcoxon test. US images clearly demonstrated the initial appearance of the ossification centers of the pisiform and sesamoid bones. These structures appeared as hyperechoic spots causing marked acoustic shadowing. The persistence of the phalangeal cartilage was depicted as a thin rim interrupting the hyperechoic cortical profile of the bone. US results were statistically equivalent to radiographic findings in the pisiform [p (op1) = .3105; p (op2) = .8886] and sesamoid bones of the thumb [p (op1) = .1386; p (op2) = .354]. A statistically significant difference between the two techniques was found in the third finger cartilage (p (op1) = .0277; p (op2) = .0759) because its profile was poorly depicted on some US images. To conclude, wrist US is proposed as a simple and valuable radiation-free support examination for the follow-up of skeletal maturation in adolescents to be submitted to orthodontic therapy.