Nanotechnologies, what are the issues in the fields of life sciences and health

Nanotechnologies have invaded our personal environment a long time ago but their contribution in the fields of life sciences and health are more recent, less frequent and essentially promises to come. We will see that the miniaturization possibilities offered by these technologies allows very attractive perspectives for in vitro diagnostic or the conception of implantable medical devices with the capacity to monitor our organism or to restore deficient physiological functions. In addition, nanoparticles can be efficiently used to treat therapeutic targets like tumors. If these technologies give rise to justified hopes they also create some concerns for a part of the population. As far as medical application are concerned, these fears are not justified because the products devoted to medical applications are subjected to very strict regulation taking into account the balance between risk and medical benefitsLes nanotechnologies ont depuis longtemps envahi le monde qui nous entoure mais leurs contributions dans les domaines des sciences de la vie et de la santé sont plus récentes, moins nombreuses et encore essentiellement des promesses à venir. Nous verrons que les capacités de « miniaturisation » offertes par ces technologies offrent des perspectives très intéressantes pour le diagnostic in vitro ou la conception d’objets très sophistiqués qui pourront être implantés dans le corps humain pour l’explorer et suppléer des fonctions déficientes. Par ailleurs, des nanoparticules peuvent être utilisées pour traiter plus efficacement des cibles thérapeutiques comme une tumeur. Si ces technologies suscitent de nombreux espoirs, elles ont aussi fait naître des craintes chez une partie du public. Dans le cas des applications destinées à la santé, ces craintes apparaissent peu justifiées. En effet, les produits de santé sont toujours soumis à une évaluation très stricte qui prend en compte le bénéfice apporté au patient en regard des risques encouru

Isolation of a cDNA clone for a catalytic subunit of Torpedo marmorata acetylcholinesterase

AbstractWe have constructed a cDNA library from Torpedo marmorata electric organ poly(A+) RNA in the lambda phage expression vector λgtll. This library has been screened with polyclonal anti-acetylcholinesterase antibodies. One clone, λAChEl, produced a fusion protein which was recognized by the antibodies and which prevented the binding of native acetylcholinesterase in an enzymatic immune assay. These results indicate that λAChEl contains a cDNA insert coding for a part of a catalytic subunit of Torpedo acetylcholinesterase. The 200-base-pair cDNA insert hybridized to three mRNAs (14.5, 10.5 and 5.5 kb) from Torpedo electric organs. These mRNAs were also detected in Torpedo electric lobes

Highly Efficient Prion Transmission by Blood Transfusion

It is now clearly established that the transfusion of blood from variant CJD (v-CJD) infected individuals can transmit the disease. Since the number of asymptomatic infected donors remains unresolved, inter-individual v-CJD transmission through blood and blood derived products is a major public health concern. Current risk assessments for transmission of v-CJD by blood and blood derived products by transfusion rely on infectious titers measured in rodent models of Transmissible Spongiform Encephalopathies (TSE) using intra-cerebral (IC) inoculation of blood components. To address the biological relevance of this approach, we compared the efficiency of TSE transmission by blood and blood components when administrated either through transfusion in sheep or by intra-cerebral inoculation (IC) in transgenic mice (tg338) over-expressing ovine PrP. Transfusion of 200 µL of blood from asymptomatic infected donor sheep transmitted prion disease with 100% efficiency thereby displaying greater virulence than the transfusion of 200 mL of normal blood spiked with brain homogenate material containing 103ID50 as measured by intracerebral inoculation of tg338 mice (ID50 IC in tg338). This was consistent with a whole blood titer greater than 103.6 ID50 IC in tg338 per mL. However, when the same blood samples were assayed by IC inoculation into tg338 the infectious titers were less than 32 ID per mL. Whereas the transfusion of crude plasma to sheep transmitted the disease with limited efficacy, White Blood Cells (WBC) displayed a similar ability to whole blood to infect recipients. Strikingly, fixation of WBC with paraformaldehyde did not affect the infectivity titer as measured in tg338 but dramatically impaired disease transmission by transfusion in sheep. These results demonstrate that TSE transmission by blood transfusion can be highly efficient and that this efficiency is more dependent on the viability of transfused cells than the level of infectivity measured by IC inoculation

Selective and Efficient Immunoprecipitation of the Disease-associated Form of the Prion Protein Can Be Mediated by Nonspecific Interactions between Monoclonal Antibodies and Scrapie-associated Fibrils

Transmissible spongiform encephalopathies are characterized by the accumulation in brain tissues of an abnormal isoform of the prion protein named PrPsc, which is the only direct marker known for transmissible spongiform encephalopathies. Here we show that PrPsc can be specifically immunoprecipitated by using several monoclonal antibodies (mAbs) of various specificities independently of the properties of their binding site (paratope). These results strongly suggest that a significant proportion of mAbs can interact with PrPsc aggregates through nonspecific paratope-independent interactions allowing selective immunoprecipitation of PrPsc when these mAbs are immobilized on a polydisperse solid phase like microbeads

The use of angiotensin receptor blockers in dementia prevention

Abstract Alzheimer’s disease (AD) and dementia are preventable and highly prevalent diseases, as is systemic arterial hypertension. Thus, it is speculated that angiotensin receptor blockers (ARBs) may be neuroprotective against AD. Objective: The aim of this study was to evaluate if the use of ARBs confers a neuroprotective effect on AD, through a systematic review. Methods: Studies published on Embase, LILACS, SciELO, and PubMed were evaluated. The selection of the studies included those that evaluated the use of antihypertensive drugs in individuals with a previous diagnosis of mild cognitive impairment. The data were extracted with the Cochrane Effective Practice and Organization of Care (EPOC) form. The risk of bias was evaluated by the EPOC “Risk of bias tool.” Results: A total of 12 articles were identified, and 3 articles were selected. Two of them analyzed the use of ARB/ACEI versus other antihypertensives and the development of dementia. Conclusion: There is a tendency for ARBs to be superior to other antihypertensives in preventing dementia

Beyond PrPres Type 1/Type 2 Dichotomy in Creutzfeldt-Jakob Disease

Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrPres and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrPSc) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrPres were identified. Despite this, the other two biochemical assays found that PrPSc from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrPSc subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrPres pattern. The identification of four different PrPSc biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability

Anti-PrP antibodies block PrPSc replication in prion-infected cell cultures by accelerating PrPC degradation.

manuscript received October 15, 2003; revised manuscript received December 15, 2003; accepted December 16, 2003. We thanks P. Rondard, O Bischof, J.-L. Laplanche and J.-P. Pin for their fruitful discussions. we are grateful to S. barrère for her assistance in the statistical analysis of the data and H. McMahon for her assistance in reading the manuscript

Diagnostic tests for human and animal prion diseases

The potential existence of clinically silent cases of bovine spongiform encephalopathy (BSE) among cattle, and of humans incubating the new variant Creutzfeldt-Jakob disease (nvCJD) is still a major public health concern. Therefore, the development of screening tests for transmissible subacute spongiform encephalopathies (TSSE) in man and animals remains a priority. In the first part of this paper, we review the main methods used to diagnose generally clinical TSSE, such as brain imaging, electroencephalogram (EEG) analysis, and cerebrospinal fluid (CSF) analysis. In the second part, we present the post-mortem tests used to confirm a TSSE diagnosis, such as inoculation to laboratory animals, histological examination, and identification of abnormal prion protein (PrPres) using biochemical methods. Finally, the third part presents so-called rapid tests (Prionics, Bio-rad, Enfer), validated by the European Commission (EC) for post-slaughter BSE diagnosis in cattle. Now used on a large scale in Europe, these tests have helped assess the extent of the epizooty and eliminate from the food chain animals presenting a risk for human consumption. Since 2002, they have been used for the post-slaughter diagnosis of scrapie in small ruminants. New tests have recently been evaluated by the EC, but it is too soon to predict their role in the field.L'existence potentielle de bovins en phase de latence cliniquement silencieuse d'encéphalopathie spongiforme bovine (ESB) et d'individus en période d'incubation de la nouvelle variante de la maladie de Creutzfeldt-Jakob représente constamment un grand risque pour la santé publique. Par conséquent, le développement de tests de dépistage des encéphalopathies spongiformes subaiguës transmissibles (ESST) humaines et animales constitue toujours une priorité. Dans la première partie de cet article, sont décrites les principales méthodes d'orientation permettant d'aider au diagnostic d'une ESST le plus souvent clinique, comme l'imagerie médicale cérébrale, l'analyse de l'électroencéphalogramme (EEG) et l'examen du liquide céphalo-rachidien. Dans la deuxième partie, sont présentés les tests de confirmation post mortem du diagnostic des ESST, comme l'inoculation à l'animal de laboratoire, l'examen histologique et la recherche de la PrPres par des méthodes biochimiques. La troisième partie est consacrée aux tests dits « rapides » (Prionics, Bio-rad, Enfer), validés en 1999 par la Commission Européenne (CE), pour le diagnostic post mortem de l'ESB à l'abattoir chez les bovins. Utilisés à grande échelle en Europe, ils ont permis de préciser l'étendue réelle de l'épizootie et d'éliminer efficacement de la chaîne alimentaire les animaux présentant un risque pour l'homme. Depuis 2002, ils sont également utilisés pour le diagnostic post mortem des petits ruminants. De nouveaux tests ont été récemment évalués par la CE, mais il est trop tôt pour évaluer la place qu'ils tiendront sur le terrain

Rapid Typing of Transmissible Spongiform Encephalopathy Strains with Differential ELISA

A strain-typing ELISA distinguishes bovine spongiform encephalopathy from other scrapie strains in small ruminants

Sympathoinhibitory effect of statins in chronic heart failure

Contains fulltext : 89087.pdf (publisher's version ) (Closed access)OBJECTIVES: Increased (central) sympathetic activity is a key feature of heart failure and associated with worse prognosis. Animal studies suggest that statin therapy can reduce central sympathetic outflow. This study assessed statin effects on (central) sympathetic activity in human chronic heart failure (CHF) patients. METHODS: Sympathetic activity was measured in eight patients with CHF patients during 8 weeks after discontinuation and 4 weeks after restart of statin therapy by microneurography for direct muscle sympathetic nerve recording (MSNA) and measurement of arterial plasma norepinephrine concentrations. RESULTS: During discontinuation of statin therapy, MSNA was significantly increased (73 +/- 4 vs. 56 +/- 5 and 52 +/- 6 bursts/100 beats, p = 0.01). Burst frequency was significantly higher after statin discontinuation (42 +/- 3 burst/min without statin vs. 32 +/- 3 and 28 +/- 3 burst/min during statin therapy, p = 0.004). Mean normalized burst amplitude and total normalized MSNA were significantly higher after statin discontinuation (mean normalized burst amplitude 0.36 +/- 0.04 without statin vs. 0.29 +/- 0.04 and 0.22 +/- 0.04 during statin, p < 0.05; total normalized MSNA 15.70 +/- 2.78 without statin, vs. 9.28 +/- 1.41 and 6.56 +/- 1.83 during statin, p = 0.009). Arterial plasma norepinephrine levels and blood pressure were unaffected. INTERPRETATION: Statin therapy inhibits central sympathetic outflow in CHF patients, as measured by MSNA.1 april 201