Poor metabolization of n-hexane in Parkinson's disease

Although genomic screening studies have identified several genes associated with Parkinson's disease (PD), there is evidence that environmental factors are also involved in the pathogenesis of the disease and that hydrocarbon-solvents may be one of them. The genetic component is less evident in late-onset PD. To assess whether age and PD may affect the catabolism of the hydrocarbon n-hexane, a two-part study was performed. In the first part the urinary levels of its main metabolites, 2,5-hexanedione and 2,5-dimethylpyrroles, were measured in 108 patients and 108 healthy controls, matched by age and sex. Metabolite urinary excretion was significantly reduced in PD patients as compared with controls and was inversely related to age in both groups. In the second part the same comparison was made between 24 non-smoking and 10 smoking patients, matched to controls, after smoking of a hydrocarbon-rich cigarette. In these subjects also n-hexane and 2,5-hexanedione blood levels were measured. There was no appreciable difference in n-hexane blood levels between patients and controls in non-smokers, whereas there was a significant increase in patients over controls in smokers (p < 0.01). 2,5-hexanedione blood levels were significantly lower in patients than in healthy controls, both in non-smokers and in smokers, but the reduction was more pronounced in smokers (−46.3 % versus −10.7 %). The same was true for 2,5-hexanedione and 2,5-dimethylpyrrole urinary levels. This study suggests that aging and PD may be associated with a reduction in the capacity to eliminate the hydrocarbon n-hexane. This metabolic alteration may play a role in the pathogenesis of PD. Received: 18 March 2002, Received in revised form: 9 October 2002, Accepted: 29 November 2002 Funding: Fondazione Grigioni per il Morbo di Parkinson Associazione Italiana Parkinsoniani. Correspondence to Gianni Pezzoli     

Insulin-like effect of zinc in mytilus digestive gland cells: modulation of tyrosine kinase-mediated cell signaling

The possible effects of zinc in the modulation of the activity of glycolytic enzymes phosphofructokinase and pyruvate kinase through tyrosine kinase-mediated signal transduction in isolated digestive gland cells from mussels (Mytilus galloprovincialis Lam.) were investigated. Addition of micromolar concentrations of zinc resulted in both time- and concentration-dependent stimulation of glycolytic enzyme activities similar to those previously observed with insulin; however, zinc pretreatment prevented the glycolytic effect of insulin in mussel cells. The insulin-like effect of zinc was mediated by increased tyrosine phosphorylation of multiple proteins, as demonstrated by Western blotting with antiphosphotyrosine antibodies. The pattern of zinc-induced phosphorylation resembled that induced by insulin. Moreover, both zinc and insulin induced activation of mitogen activated protein kinases (MAPKs); however, whereas zinc gave a clear effect on the stress-activated p-38 MAPK, insulin activated extracellular-activated MAPK (ERK2) and inhibited p-38. The results demonstrate that zinc can act as a physiological regulator of tyrosine kinase-mediated cell signaling in mussel digestive gland cells, in particular at the level of MAPK activation. Activation of p-38 by zinc may be a key step in prevention of the glycolytic effect of insulin in mussel cells. These data underline the importance of cross talk between different MAPKs in determination of the response to extracellular stimuli in marine invertebrate cells.     

Proinflammatory lipoxygenase products from peripheral mononuclear cells in patients with rheumatoid arthritis

The formation of 5-lipoxygenase products (5-hydroxyeicosatetraenoic acid [5-HETE], leukotriene B4 [LTB4], and leukotriene C4 [LTC4]) by polymorphonuclear and mononuclear leukocytes isolated from peripheral blood of patients with rheumatoid arthritis was evaluated and compared with the data obtained from a group of control subjects. Although the levels of arachidonic acid metabolites via 5-lipoxygenase pathway by stimulated polymorphonuclear cells were comparable between patients and controls, mononuclear leukocytes from patients synthesized, when stimulated, significantly greater amounts of 5-HETE, LTB4, and LTC4 than did cells isolated from normal subjects. In addition, the release of superoxide anion, stimulated by either a particulate or a soluble stimulus, was increased in mononuclear cells from patients. The enhanced capacity of peripheral mononuclear leukocytes isolated from patients with rheumatoid arthritis to generate proinflammatory metabolites of arachidonic acid and oxygenated species with bactericidal and tissue-damaging properties may contribute to the pathogenesis of this complex disease.     

Analysis of ferritin genes in Parkinson disease.

BACKGROUND: Genes that regulate iron metabolism may be involved in increasing brain iron content in Parkinson disease (PD). The ferritin L-chain is one of these genes, but the rare insertional mutations that cause neuroferritinopathy with basal ganglia degeneration have not yet been identified in PD. METHODS: We used denaturing HPLC (DHPLC) to investigate 124 PD patients and 180 controls for variations in the coding and in the 5' untranslated regions of the H- and L-ferritin genes. RESULTS: In the H-ferritin gene, we found one new and rather common intronic polymorphism and the K54R substitution in two controls. The L-ferritin gene showed a very common L55L polymorphism and four other types of DNA variations, three of which were in the patient cohort. A mutation of the conserved His133 to Pro was found in a PD patient and in his daughter. The patient did not show signs of neuroferritinopathy, but the mutation was associated with low L-ferritin levels and with mild chronic anemia. CONCLUSIONS: The results support the hypothesis that DNA variations in the ferritin genes are not a common cause for PD.     

Correction to: Caregiver burden and its related factors in advanced Parkinson’s disease: data from the PREDICT study

Journal of Neurology - The original version of this article unfortunately contained a mistake. In the Figure     

Parkin analysis in early onset Parkinson's disease

We analysed the parkin gene in a large consecutive series (146) of unrelated early onset Parkinson's disease (onset ⩽40 years of age) patients. Twelve cases (8.2%) had homozygous or compound heterozygous point mutations and/or exon rearrangements, while a single mutation was found in four subjects (2.7%). We identified eight exon rearrangements and nine point mutations, two of which were novel: c.735delT (p.C212/X224) and c.815C>G (p.C238W). Genotype–phenotype correlation revealed that parkin carriers had features similar to those of non-carrier early onset Parkinson disease patients.     

Early abnormalities of vascular and cardiac autonomic control in Parkinson's disease without orthostatic hypotension

Cardiac autonomic abnormalities have been described in Parkinson's disease. Little is known about possible alterations of vascular sympathetic regulatory activity in patients without orthostatic hypotension or symptoms of orthostatic intolerance. Nineteen patients with Parkinson's disease without orthostatic hypotension (PD), 21 with orthostatic hypotension (PDOH), and 20 healthy controls underwent ECG, beat-to-beat arterial pressure, and respiration recordings while recumbent and during a 75 degrees head-up tilt. Spectrum analysis of RR interval and systolic arterial pressure (SAP) variability provided indices of cardiac sympathovagal interaction (low frequency [LF]/high frequency [HF]) to the sinoatrial node and sympathetic vasomotor control (LF(SAP)). Arterial baroreceptor mechanisms were assessed by the spontaneous sequences technique and bivariate spectrum analysis (alpha index). Plasma catecholamines provided the neurohormonal profile. At rest, hemodynamics and spectral markers of autonomic function were similar in PD and control subjects. Norepinephrine was lower in PD and PDOH than in control subjects. In PDOH, SAP was higher, whereas LF/HF ratio and LF(SAP) were lower compared with control subjects. During tilt, SAP was unchanged in PD; however, similar to PDOH, the increase of heart rate, LF/HF ratio, and LF(SAP) was blunted compared with control subjects. Baroreflex indices were unmodified in PD and PDOH compared with control subjects. Initial alterations in both cardiac and vascular sympathetic modulatory activity were found in PD and revealed by a gravitational stimulus. Prompt recognition of sympathetic abnormalities might result in earlier therapeutic intervention, reduced orthostatic intolerance, and increased quality of life.