Katsaus lisäävän valmistuksen (aka 3D-tulostus) mahdollisuuksiin ja kustannuksiin metallisten tuotteiden valmistuksessa: Case jauhepetitekniikka

Suurelle yleisölle lisäävä valmistustekniikka eli ns. 3D-tulostustekniikka näyttäytyy lehtien otsikoissa ja artikkeleissa esiin pulpahtavana ”muotiaiheena”, mutta sekä muovien 3D-tulostustekniikka että metallienkin vastaava valmistustekniikka on ollut olemassa maailmalla ja Suomessa 80-luvun puolivälistä alkaen. Yhdysvalloissa ja Saksassa tekniikkaa käytetään valmistavassa teollisuudessa toiminnallisten osien tuotannossa. Esimerkiksi lentokoneen suihkumoottorien osia ja lääketieteellisiä välineitä tehdään metallijauheesta lisäävän valmistuksen avulla. Itse asiassa eräs menetelmä metalliesineiden valmistamiseksi lasersäteen avulla keksittiin Suomessa ja sitä myös kehiteltiin täällä, mutta teollisuudenala lähti aikanaan nousuun Saksassa. Lisäävä valmistus on tällä hetkellä maailmanlaajuisesti eräs kiinnostavista tuotantotekniikoista, jonka uskotaan muuttavan monia asioita tuotteiden suunnittelussa, toiminnoissa ja valmistuksessa. Tämä tekniikka ei kiinnosta pelkästään valmistavaa teollisuutta, vaan tietotekniikan, lääketieteen, koruvalmistuksen ja muotoilun osaajat sekä uusien liiketoimintamallien kehittäjät ja logistiikka operaattorit ovat teknologiasta kiinnostuneita. Suomelle 3D-tulostustekniikka on suuri mahdollisuus, sillä maassamme on vahva teollinen tieto- ja viestintätekniikkaosaaminen sekä lisäksi olemme maassamme erikoistuneet varsin vaativien teollisiin laitteiden valmistukseen. Eräät suurimmista mahdollisuuksista tällä tekniikalla ovat toimitusketjuihin liittyvät muutokset. Uutta on, että pienetkin yritykset ja organisaatiot voivat soveltaa tätä tekniikkaa valmistuksessa ja jopa kehitellä täysin uusia tuotteita. On myös arvioitu, että lisäävän valmistuksen merkitys valmistustapoihin ja toimitusketjuihin voi olla suurempi kuin koskaan aikaisemmin minkään teknologisen uudistuksen kohdalla. Lisäävästä valmistuksesta usein puhutaankin kolmantena teollisena vallankumouksena juuri tämän takia. 3D-tulostuksen kustannuksia tarkasteltaessa on tärkeätä huomata että vain sulatetun jauheen määrä ratkaisee, ei käytettävän geometrian monimutkaisuus. Tämä erottaa perinteisen ja lisäävän valmistuksen toisistaan. Perinteisesti kappaleen keventäminen on maksanut ”ylimääräistä”, kun taas lisäävässä valmistuksessa kappaleen keveys on jopa kustannusta alentava tekijä. Valmistettavan kappaleen korkeus on yksi kriittisimpiä kustannuksiin vaikuttavia tekijöitä. Tämän vuoksi useamman kappaleen valmistus yhdellä kertaa parantaa kannattavuutta huomattavasti. Samalla kertaa voi ja itse asiassa kannattaakin valmistaa keskenään erilaisia kappaleita. Perinteiset valmistustavat sen sijaan ovat nykyajan vaatimuksille liian hitaita; ne joustavat huonosti, kun kyseessä on pienet, asiakaslähtöiset erät. Trendi on globaalisti kohden yksilöllisiä asiakaslähtöisiä tuotteita, jolloin myös valmistustekniikoiden on oltava joustavia pysyäkseen näiden vaatimusten perässä. Lisäävä valmistus sopii erityisesti hyvin piensarjatuotantoon. Suuremmissa valmistuserissä kuitenkin perinteiset tekniikat ovat kustannustehokkaampia.

A direct contact between astrocyte and vitreous body is possible in the rabbit eye due to discontinuities in the basement membrane of the retinal inner limiting membrane

Different from most mammalian species, the optic nerve of the rabbit eye is initially formed inside the retina where myelination of the axons of the ganglion cells starts and vascularization occurs. Astrocytes are confined to these regions. The aforementioned nerve fibers known as medullated nerve fibers form two bundles that may be identified with the naked eye. The blood vessels run on the inner surface of these nerve fiber bundles (epivascularization) and, accordingly, the accompanying astrocytes lie mostly facing the vitreous body from which they are separated only by the inner limiting membrane of the retina. The arrangement of the astrocytes around blood vessels leads to the formation of structures known as glial tufts. Fragments (N = 3) or whole pieces (N = 3) of the medullated nerve fiber region of three-month-old male rabbits (Orictolagus cuniculus) were fixed in glutaraldehyde followed by osmium tetroxide, and their thin sections were examined with a transmission electron microscope. Randomly located discontinuities (up to a few micrometers long) of the basement membrane of the inner limiting membrane of the retina were observed in the glial tufts. As a consequence, a direct contact between the astrocyte plasma membrane and vitreous elements was demonstrated, making possible functional interactions such as macromolecular exchanges between this glial cell type and the components of the vitreous body.

Fabrication additive ou Impression 3D. Aperçus sur une variation terminographique

Materiaalia lisäävä valmistus eli 3D-tulostus on valmistusmenetelmä, jossa kappale tehdään 3D-mallin pohjalta materiaalikerroksia lisäämällä, käyttäen useita tekniikoita ja materiaaleja. Menetelmää sovelletaan useilla teollisuuden aloilla. Lisääviä valmistustekniikoita on kehitetty 1990-luvun alkupuolelta lähtien, ja ne monipuolistuvat jatkuvasti. Tässä pro gradu -tutkielmassa tutkitaan sovellusalan terminologian kehitystä vertailevilla menetelmillä ja luodaan kolmikielinen sanasto alan asiantuntijoille, joita edustaa Suomessa FIRPA ry. Sanaston kielet ovat englanti, ranska ja suomi. Terminologian tutkimus on perinteisesti keskittynyt sanastotyöhön ja käsiteanalyysiin, sen sijaan termihistorian tutkimus on ollut vähäisempää. Tässä työssä on tehty vertailevaa termitutkimusta sekä sanastotyön että termihistorian näkökulmista. Vertailutasoja ovat termien merkityksen muuttuminen, vertailu pivot-kielen suhteen ja kielikohtaisten ominaisuuksien tarkastelu termien muotoutumisessa. Tutkittavia asioita ovat sanastokäsitteiden väliset suhteet, synonyymien, varianttien ja uudissanojen moninaisuus, ja termien yleiskielistyminen. Samalla pohditaan muita termien muuttumiseen vaikuttavia syita. Tärkeimpänä lähteenä käytetään Wohlersin vuosiraportteja, jotka kuvaavat kattavasti koko teollisuudenalaa. Koska englannin pivot-vaikutus on voimakasta teknisillä aloilla, omankielisen terminologian kehittyminen vaatii tietoista terminologiatyötä ja aktiivista omankielisten termien käyttöä. Terminologian vakiintumista voidaan arvioida termivarianttien ja uudissanojen määristä, sekä termien yleiskielistymisestä. Terminologia muuttuu jatkuvasti toimialan kehittyessä ja vaatii säännöllistä päivittämistä. Termihistorian tunteminen tukee sanastotyön termivalintoja. Alan asiantuntijat ovat vastuussa omasta terminologiastaan, ja heidän aktiivisuutensa on tärkeää sen kehittämisessä. Toteutettu sanasto on tämän pro gradu -tutkielman liitteenä ja se julkaistaan myös FIRPA ry:n Internet-sivustolla. Suomenkielinen osio sanastosta on ensimmäinen laaja suomeksi julkaistu materiaalia lisäävän valmistuksen sanasto.

Lightweight, liquid-cooled, direct-drive generator for highpower wind turbines: motivation, concept, and performance

Thesis: A liquid-cooled, direct-drive, permanent-magnet, synchronous generator with helical, double-layer, non-overlapping windings formed from a copper conductor with a coaxial internal coolant conduit offers an excellent combination of attributes to reliably provide economic wind power for the coming generation of wind turbines with power ratings between 5 and 20MW. A generator based on the liquid-cooled architecture proposed here will be reliable and cost effective. Its smaller size and mass will reduce build, transport, and installation costs. Summary: Converting wind energy into electricity and transmitting it to an electrical power grid to supply consumers is a relatively new and rapidly developing method of electricity generation. In the most recent decade, the increase in wind energy’s share of overall energy production has been remarkable. Thousands of land-based and offshore wind turbines have been commissioned around the globe, and thousands more are being planned. The technologies have evolved rapidly and are continuing to evolve, and wind turbine sizes and power ratings are continually increasing. Many of the newer wind turbine designs feature drivetrains based on Direct-Drive, Permanent-Magnet, Synchronous Generators (DD-PMSGs). Being low-speed high-torque machines, the diameters of air-cooled DD-PMSGs become very large to generate higher levels of power. The largest direct-drive wind turbine generator in operation today, rated just below 8MW, is 12m in diameter and approximately 220 tonne. To generate higher powers, traditional DD-PMSGs would need to become extraordinarily large. A 15MW air-cooled direct-drive generator would be of colossal size and tremendous mass and no longer economically viable. One alternative to increasing diameter is instead to increase torque density. In a permanent magnet machine, this is best done by increasing the linear current density of the stator windings. However, greater linear current density results in more Joule heating, and the additional heat cannot be removed practically using a traditional air-cooling approach. Direct liquid cooling is more effective, and when applied directly to the stator windings, higher linear current densities can be sustained leading to substantial increases in torque density. The higher torque density, in turn, makes possible significant reductions in DD-PMSG size. Over the past five years, a multidisciplinary team of researchers has applied a holistic approach to explore the application of liquid cooling to permanent-magnet wind turbine generator design. The approach has considered wind energy markets and the economics of wind power, system reliability, electromagnetic behaviors and design, thermal design and performance, mechanical architecture and behaviors, and the performance modeling of installed wind turbines. This dissertation is based on seven publications that chronicle the work. The primary outcomes are the proposal of a novel generator architecture, a multidisciplinary set of analyses to predict the behaviors, and experimentation to demonstrate some of the key principles and validate the analyses. The proposed generator concept is a direct-drive, surface-magnet, synchronous generator with fractional-slot, duplex-helical, double-layer, non-overlapping windings formed from a copper conductor with a coaxial internal coolant conduit to accommodate liquid coolant flow. The novel liquid-cooling architecture is referred to as LC DD-PMSG. The first of the seven publications summarized in this dissertation discusses the technological and economic benefits and limitations of DD-PMSGs as applied to wind energy. The second publication addresses the long-term reliability of the proposed LC DD-PMSG design. Publication 3 examines the machine’s electromagnetic design, and Publication 4 introduces an optimization tool developed to quickly define basic machine parameters. The static and harmonic behaviors of the stator and rotor wheel structures are the subject of Publication 5. And finally, Publications 6 and 7 examine steady-state and transient thermal behaviors. There have been a number of ancillary concrete outcomes associated with the work including the following. X Intellectual Property (IP) for direct liquid cooling of stator windings via an embedded coaxial coolant conduit, IP for a lightweight wheel structure for lowspeed, high-torque electrical machinery, and IP for numerous other details of the LC DD-PMSG design X Analytical demonstrations of the equivalent reliability of the LC DD-PMSG; validated electromagnetic, thermal, structural, and dynamic prediction models; and an analytical demonstration of the superior partial load efficiency and annual energy output of an LC DD-PMSG design X A set of LC DD-PMSG design guidelines and an analytical tool to establish optimal geometries quickly and early on X Proposed 8 MW LC DD-PMSG concepts for both inner and outer rotor configurations Furthermore, three technologies introduced could be relevant across a broader spectrum of applications. 1) The cost optimization methodology developed as part of this work could be further improved to produce a simple tool to establish base geometries for various electromagnetic machine types. 2) The layered sheet-steel element construction technology used for the LC DD-PMSG stator and rotor wheel structures has potential for a wide range of applications. And finally, 3) the direct liquid-cooling technology could be beneficial in higher speed electromotive applications such as vehicular electric drives.

Foreign Direct Investment and Shareholder Wealth Gains: Evidence from Finnish FDI in China

In Finnish discourse, “The China Effect” refers to the surge of offshoring activities by Western companies to China during the past couple of decades. Inspired by event studies concerning announcements of foreign direct investment, this thesis investigates the market’s reaction to Finnish companies’ announcement of FDI targeting the People’s Republic of China. Standard event study methodology is applied to 135 announcements related to subsidiaries, joint ventures and acquisitions between 1997 and 2014. The data is checked for contamination by unrelated coinciding events and outliers. A positive average abnormal return is found to take place on the date of the announcement. Additionally, the abnormal returns are found to exist only for projects announced before 2008, and only when the investment project is new, as opposed to investments made to extend previously established projects. Ownership arrangement and the novelty of facilities do not influence the market’s reaction towards the investment announcement.

3D-tulostustekniikan hyödyntäminen diagnostisten pikatestien tuotekehityksessä

Pikamallinnustekniikat ovat kehittyneet viime vuosina nopeasti. Tämä antaa jo lähes rajat-tomat mahdollisuudet tuottaa 3D-tulostamalla erilaisia tuotteita. 3D-tulostuksen hyödyntä-minen on yleistynyt erityisesti teollisuuden ja teknologian aloilla. Tässä työssä tutkittiin miten 3D-tulostamista voidaan hyödyntää diagnostisten pikatestien tuotekehityksessä. Immunologinen lateral flow-testi on vasta-aineisiin perustuva, nopea ja helppokäyttöinen mittausmenetelmä pienten ainemäärien havaitsemiseen. Tässä työssä kehitettiin lateral flow-testikotelo, jonka suunnitteluun ja rakenteen mallintamiseen käytettiin 3D-tulostustekniikkaa. Testikotelon toimivuus lateral flow- testissä varmistettiin kehittämällä testikoteloon sopiva pikatesti, jonka suorituskykyä analysoitiin sekä visuaalisesti että Actim 1ngeni-lukulaitteella. Työ aloitettiin tutkimalla eri pikavalmistustekniikoita, joista testikotelon tulostamiseen valittiin SLA-tekniikka sen tulostustarkkuuden ja tuotteen pinnan laadun perusteella. Testikotelon suunnittelu aloitettiin määrittämällä millaisia ominaisuuksia testikotelolta haluttiin. Näitä ominaisuuksia olivat lateral flow-testin suojaaminen sekä testissä kulkevan näytteen virtauksen varmistamien. Lateral flow- testin kehityksessä hyödynnettiin osin aiemmin kehitetystä pikatestistä saatuja tietoja. Lateral flow- kasettitestin valmistusprosessi koostui seitsemästä eri prosessivaiheesta jotka olivat: Vasta-aineen/kontrollireagenssin konjugointi, näytetyynyn käsittely, konjugointityynyn käsittely, konjugointityynylle annostelu, membraanille annostelu, tikkujen laminointi ja leikkaus sekä kasettitestin kokoonpano. Kehitetyn lateral flow- kasettitestin toimivuus varmistettiin tutkimalla testin reaktiokinetiikkaa ja analyyttistä herkkyyttä sekä visuaalisesti että lukulaitteen avulla. Tutkimustulosten perusteella 3D-tulostus on erittäin hyödyllinen menetelmä pikatestien tuotekehityksessä suunniteltaessa testikotelorakenteita, näytteen annosteluvälineitä ja näiden yhdistelmiä.

Direct-Driven Interior Magnet Permanent Magnet Synchronous Motors for a Full Electric Sports Car

The design process of direct-driven permanent magnet synchronous machines (PMSMs) for a full electric 4 ´ 4 sports car is presented. The rotor structure of the machine consists of two permanent magnet layers embedded inside the rotor laminations thus resulting in some inverse saliency, where the q-axis inductance is larger than the d-axis one. An integer slot stator winding was selected to fully take advantage of the additional reluctance torque. The performance characteristics of the designed PMSMs were calculated by applying a twodimensional finite element method. Cross-saturation between the d- and q-axes was taken into account in the calculation of the synchronous inductances. The calculation results are validated by measurements.

Design and Drive-Cycle Based Analysis of Direct-Driven Permanent Magnet Synchronous Machine for a Small Urban Use Electric Vehicle

A direct-driven permanent magnet synchronous machine for a small urban use electric vehicle is presented. The measured performance of the machine at the test bench as well as the performance over the modified New European Drive Cycle will be given. The effect of optimal current components, maximizing the efficiency and taking into account the iron loss, is compared with the simple id=0 – control. The machine currents and losses during the drive cycle are calculated and compared with each other.

Foreign Direct Investment, Clean Development Mechanism, and Environmental Management: A case of Sub-Saharan Africa

This doctoral dissertation explores the contribution of environmental management practices, the so-called clean development mechanism (CDM) projects, and foreign direct investment (FDI) in achieving sustainable development in developing countries, particularly in Sub- Saharan Africa. Because the climate change caused by greenhouse gas emissions is one of the most serious global environmental challenges, the main focus is on the causal links between carbon dioxide (CO2) emissions, energy consumption, and economic development in Sub-Saharan Africa. In addition, the dissertation investigates the factors that have affected the distribution of CDM projects in developing countries and the relationships between FDI and other macroeconomic variables of interest. The main contribution of the dissertation is empirical. One of the publications uses crosssectional data and Tobit and Poisson regressions. Three of the studies use time-series data and vector autoregressive and vector error correction models, while two publications use panel data and panel data estimation methods. One of the publications uses thus both timeseries and panel data. The concept of Granger causality is utilized in four of the publications. The results indicate that there are significant differences in the Granger causality relationships between CO2 emissions, energy consumption, economic growth, and FDI in different countries. It appears also that the causality relationships change over time. Furthermore, the results support the environmental Kuznets curve hypothesis but only for some of the countries. As to CDM activities, past emission levels, institutional quality, and the size of the host country appear to be among the significant determinants of the distribution of CDM projects. FDI and exports are also found to be significant determinants of economic growth.

Direct costs of asthma in Brazil: a comparison between controlled and uncontrolled asthmatic patients

Asthma is a common chronic illness that imposes a heavy burden on all aspects of the patient's life, including personal and health care cost expenditures. To analyze the direct cost associated to uncontrolled asthma patients, a cross-sectional study was conducted to determine costs related to patients with uncontrolled and controlled asthma. Uncontrolled patient was defined by daytime symptoms more than twice a week or nocturnal symptoms during two consecutive nights or any limitations of activities, or need for relief rescue medication more than twice a week, and an ACQ score less than 2 points. A questionnaire about direct cost stratification in health services, including emergency room visits, hospitalization, ambulatory visits, and asthma medications prescribed, was applied. Ninety asthma patients were enrolled (45 uncontrolled/45 controlled). Uncontrolled asthmatics accounted for higher health care expenditures than controlled patients, US$125.45 and US$15.58, respectively [emergency room visits (US$39.15 vs US$2.70) and hospitalization (US$86.30 vs US$12.88)], per patient over 6 months. The costs with medications in the last month for patients with mild, moderate and severe asthma were US$1.60, 9.60, and 25.00 in the uncontrolled patients, respectively, and US$6.50, 19.00 and 49.00 in the controlled patients. In view of the small proportion of uncontrolled subjects receiving regular maintenance medication (22.2%) and their lack of resources, providing free medication for uncontrolled patients might be a cost-effective strategy for the public health system.

Sulautetun ohjausjärjestelmän kehittäminen 3D-tulostimelle

Kandidaatintyössä tutkittiin Adam Klodowskin tutkimuksessa käytetyn menetelmän soveltuvuutta 3D-tulostimen mekanismiin. Tutkimustyö liittyy RepRap-projektiin, jonka tavoitteena on valmistaa 3D-tulostin 3D-tulostetuista osista. Mekaniikasta oli luotu matemaattinen malli, jota tutkittiin simuloinnin avulla. Työssä toteutettiin täysin yksilöity sulautettu ohjausjärjestelmä kyseiselle mekanismille ja tutkittiin järjestelmän soveltuvuutta käytäntöön. Tavoitteena oli vähentää komponenttien lukumäärää ja pienentää laitteiston vaatimaa tilaa.

Molecular analysis of the bovine coronavirus S1 gene by direct sequencing of diarrheic fecal specimens

Bovine coronavirus (BCoV) causes severe diarrhea in newborn calves, is associated with winter dysentery in adult cattle and respiratory infections in calves and feedlot cattle. The BCoV S protein plays a fundamental role in viral attachment and entry into the host cell, and is cleaved into two subunits termed S1 (amino terminal) and S2 (carboxy terminal). The present study describes a strategy for the sequencing of the BCoV S1 gene directly from fecal diarrheic specimens that were previously identified as BCoV positive by RT-PCR assay for N gene detection. A consensus sequence of 2681 nucleotides was obtained through direct sequencing of seven overlapping PCR fragments of the S gene. The samples did not undergo cell culture passage prior to PCR amplification and sequencing. The structural analysis was based on the genomic differences between Brazilian strains and other known BCoV from different geographical regions. The phylogenetic analysis of the entire S1 gene showed that the BCoV Brazilian strains were more distant from the Mebus strain (97.8% identity for nucleotides and 96.8% identity for amino acids) and more similar to the BCoV-ENT strain (98.7% for nucleotides and 98.7% for amino acids). Based on the phylogenetic analysis of the hypervariable region of the S1 subunit, these strains clustered with the American (BCoV-ENT, 182NS) and Canadian (BCQ20, BCQ2070, BCQ9, BCQ571, BCQ1523) calf diarrhea and the Canadian winter dysentery (BCQ7373, BCQ2590) strains, but clustered on a separate branch of the Korean and respiratory BCoV strains. The BCoV strains of the present study were not clustered in the same branch of previously published Brazilian strains (AY606193, AY606194). These data agree with the genealogical construction and suggest that at least two different BCoV strains are circulating in Brazil.

Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation

Lopap, found in the bristles of Lonomia obliqua caterpillar, is the first exogenous prothrombin activator that shows serine protease-like activity, independent of prothrombinase components and unique lipocalin reported to interfere with hemostasis mechanisms. To assess the action of an exogenous prothrombin activator reversing the anticoagulant and antihemostatic effect induced by low molecular weight heparin (LMWH), male New Zealand rabbits (N = 20, weighing 3.8-4.0 kg) allocated to 4 groups were anticoagulated with 1800 IU/kg LMWH (iv) over 2 min, followed by iv administration of saline (SG) or recombinant Lopap (rLopap) at 1 µg/kg (LG1) or 10 µg/kg (LG10), 10 min after the injection of LMWH, in a blind manner. Control animals (CG) were treated only with saline. The action of rLopap was assessed in terms of activated partial thromboplastin time (aPTT), prothrombin fragment F1+2, fibrinogen, and ear puncture bleeding time (BT) at 5, 10, 15, 17, 20, 30, 40, 60, and 90 min after initiation of LMWH infusion. LG10 animals showed a decrease of aPTT in more than 50% and BT near to normal baseline. The level of prothrombin fragment F1+2 measured by ELISA had a 6-fold increase with rLopap treatment (10 µg/kg) and was inversely proportional to BT in LMWH-treated animals. Thus, Lopap, obtained in recombinant form using E. coli expression system, was useful in antagonizing the effect of LMWH through direct prothrombin activation, which can be a possible strategy for the reversal of bleeding and anticoagulant events.

Transcranial direct current stimulation and repetitive transcranial magnetic stimulation in consultation-liaison psychiatry

Patients with clinical diseases often present psychiatric conditions whose pharmacological treatment is hampered due to hazardous interactions with the clinical treatment and/or disease. This is particularly relevant for major depressive disorder, the most common psychiatric disorder in the general hospital. In this context, nonpharmacological interventions could be useful therapies; and, among those, noninvasive brain stimulation (NIBS) might be an interesting option. The main methods of NIBS are repetitive transcranial magnetic stimulation (rTMS), which was recently approved as a nonresearch treatment for some psychiatric conditions, and transcranial direct current stimulation (tDCS), a technique that is currently limited to research scenarios but has shown promising results. Therefore, our aim was to review the main medical conditions associated with high depression rates, the main obstacles for depression treatment, and whether these therapies could be a useful intervention for such conditions. We found that depression is an important and prevalent comorbidity in a variety of diseases such as epilepsy, stroke, Parkinson's disease, myocardial infarction, cancer, and in other conditions such as pregnancy and in patients without enteral access. We found that treatment of depression is often suboptimal within the above contexts and that rTMS and tDCS therapies have been insufficiently appraised. We discuss whether rTMS and tDCS could have a significant impact in treating depression that develops within a clinical context, considering its unique characteristics such as the absence of pharmacological interactions, the use of a nonenteral route, and as an augmentation therapy for antidepressants.

Estragole blocks neuronal excitability by direct inhibition of Na+ channels

Estragole is a volatile terpenoid, which occurs naturally as a constituent of the essential oils of many plants. It has several pharmacological and biological activities. The objective of the present study was to investigate the mechanism of action of estragole on neuronal excitability. Intact and dissociated dorsal root ganglion neurons of rats were used to record action potential and Na+ currents with intracellular and patch-clamp techniques, respectively. Estragole blocked the generation of action potentials in cells with or without inflexions on their descendant (repolarization) phase (Ninf and N0 neurons, respectively) in a concentration-dependent manner. The resting potentials and input resistances of Ninf and N0 cells were not altered by estragole (2, 4, and 6 mM). Estragole also inhibited total Na+ current and tetrodotoxin-resistant Na+ current in a concentration-dependent manner (IC50 of 3.2 and 3.6 mM, respectively). Kinetic analysis of Na+ current in the presence of 4 mM estragole showed a statistically significant reduction of fast and slow inactivation time constants, indicating an acceleration of the inactivation process. These data demonstrate that estragole blocks neuronal excitability by direct inhibition of Na+ channel conductance activation. This action of estragole is likely to be relevant to the understanding of the mechanisms of several pharmacological effects of this substance.