French Institute of Health and Medical Research

About: French Institute of Health and Medical Research is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 109367 authors who have published 174236 publications receiving 8365503 citations.

Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia.

Abstract: Levels of iron, copper, zinc and manganese were measured by inductively coupled plasma spectroscopy in frozen postmortem brain tissue from patients with Parkinson's disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy with strionigral degeneration (MSA), and Huntington's disease (HD) compared with control subjects. Total iron levels were found to be elevated in the areas of basal ganglia showing pathological change in these disorders. In particular, total iron content was increased in substantia nigra in PD, PSP and MSA, but not in HD. Total iron levels in the striatum (putamen and/or caudate nucleus) were increased in PSP, MSA and HD but not in PD. Total iron levels were decreased in the globus pallidus in PD. There were no consistent alterations of manganese levels in basal ganglia structures in any of the diseases studied. Copper levels were decreased in the substantia nigra in PD, and in the cerebellum in PSP, and were elevated in the putamen and possibly substantia nigra in HD. Zinc levels were only increased in PD, in substantia nigra and in caudate nucleus and lateral putamen. Levels of the iron binding protein ferritin were measured in the same patient groups using a radio-immunoassay technique. Increased iron levels in basal ganglia were generally associated with normal or elevated levels of ferritin immunoreactivity, for example, the substantia nigra in PSP and possibly MSA, and in putamen in MSA. The exception was PD where there was a generalized reduction in brain ferritin immunoreactivity, even in the substantia nigra. An increase in total iron content appears to be a response to neurodegeneration in affected basal ganglia regions in a number of movement disorders. However, only in PD was there an increased total iron level, decreased ferritin content, decreased copper content, and an increased zinc concentration in substantia nigra. These findings suggest an alteration of iron handling in the substantia nigra in PD. Depending on the form in which the excess iron load exists in nigra in PD, it may contribute to the neurodegenerative process.

Clinical and Genetic Abnormalities in Patients with Friedreich's Ataxia

Abstract: Background Friedreich's ataxia, the most common inherited ataxia, is associated with a mutation that consists of an unstable expansion of GAA repeats in the first intron of the frataxin gene on chromosome 9, which encodes a protein of unknown function. Methods We studied 187 patients with autosomal recessive ataxia, determined the size of the GAA expansions, and analyzed the clinical manifestations in relation to the number of GAA repeats and the duration of disease. Results One hundred forty of the 187 patients, with ages at onset ranging from 2 to 51 years, were homozygous for a GAA expansion that had 120 to 1700 repeats of the trinucleotides. About one quarter of the patients, despite being homozygous, had atypical Friedreich's ataxia; they were older at presentation and had intact tendon reflexes. Larger GAA expansions correlated with earlier age at onset and shorter times to loss of ambulation. The size of the GAA expansions (and particularly that of the smaller of each pair) was associated with the ...

Cholesterol, inflammation and innate immunity

Abstract: Hypercholesterolaemia leads to cholesterol accumulation in macrophages and other immune cells, which promotes inflammatory responses, including augmentation of Toll-like receptor (TLR) signalling, inflammasome activation, and the production of monocytes and neutrophils in the bone marrow and spleen. On a cellular level, activation of TLR signalling leads to decreased cholesterol efflux, which results in further cholesterol accumulation and the amplification of inflammatory responses. Although cholesterol accumulation through the promotion of inflammatory responses probably has beneficial effects in the response to infections, it worsens diseases that are associated with chronic metabolic inflammation, including atherosclerosis and obesity. Therapeutic interventions such as increased production or infusion of high-density lipoproteins may sever the links between cholesterol accumulation and inflammation, and have beneficial effects in patients with metabolic diseases.

Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis

Abstract: Changes of bone turnover with aging are responsible for bone loss and play a major role in osteoporosis Although an increase of bone turnover has been documented at the time of menopause, the subsequent abnormalities of bone resorption and formation and their potential role in determining bone mass in the elderly have not been investigated To address this issue, we have measured a battery of new sensitive and specific markers of bone turnover in a population-based study of 653 healthy women analyzed cross-sectionally, including 432 women postmenopausal from 1 to 40 years, and the data were correlated with bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at different skeletal sites Bone formation was assessed by serum osteocalcin (OC), serum bone-specific alkaline phosphatase (B-ALP), serum C-propeptide of type I collagen (PICP), and bone resorption by the urinary excretion of two pyridinoline cross-linked peptides (NTX and CTX) Bone turnover increased in perimenopausal women with both irregular menses and elevated serum follicle stimulating hormone (FSH) Menopause induced a 37-52% and 79-97% increase in the bone formation and bone resorption marker levels, respectively (p < 00001 except for PICP) In postmenopausal women, bone formation markers did not decrease with age When resorption markers were corrected by whole body bone mineral content (BMC), the fraction of bone resorbed per day was not correlated with age in postmenopausal women and remained elevated for up to 40 years after menopause In premenopausal women, the bone turnover rate accounted for only 0-10% of the variation in whole body BMC, total hip, distal radius, and lumbar spine BMD With increasing time after menopause, the importance of the bone turnover rate as a determinant of bone mass increased at all sites and accounted for up to 52% of the BMD variance in elderly women Thus, in women 20 years or more postmenopause, bone turnover was higher in those in the lowest quartile than in those in the highest quartile of BMD In elderly women, 20 years since menopause and over, but not in younger ones, serum PTH was negatively correlated with serum 25-hydroxyvitamin D (r = -022, p < 005) and explained only 5-8% of the bone turnover variance (p < 001-0001) These data indicate that the overall rates of both bone formation and bone resorption remain high in elderly women The rate of bone turnover appears to play an increasing role as a determinant of bone mass with increasing time since menopause with a high bone turnover rate being associated with a low bone mass Thus assessing bone marker levels may be useful in the evaluation of osteoporosis risk In elderly women, secondary hyperparathyroidism caused in part by reduced serum 25-hydroxyvitamin D appears to be a marginal determinant of an increased bone turnover rate