Fordson - produktivare jordbruk fördelaktigare transport

kuv., 24 x 12 cm

Transport-küsimuse lahendus

kuv., 14 x 22 cm

1936 Ford V-8 alltid redo till ekonomisk transport

kuv., 17 x 23 cm

JNK, a versatile regulator of kinesin-1 transport and cytoskeleton dynamics

C-Jun N-terminal kinase (JNK) is traditionally recognized as a crucial factor in stress response and inducer of apoptosis upon various stimulations. Three isoforms build the JNK subfamily of MAPK; generally expressed JNK1 and JNK2 and brain specific JNK3. Degenerative potency placed JNK in the spotlight as potential pharmacological option for intervention. Unfortunately, adverse effects of potential drugs and observation that expression of only JNK2 and JNK3 are induced upon stress, restrained initial enthusiasm. Notably, JNK1 demonstrated atypical high constitutive activity in neurons that is not responsive to cellular stresses and indicated existence of physiological activity. This thesis aimed at revealing the physiological functions of JNK1 in actin homeostasis through novel effector MARCKS-Like 1 (MARCKSL1) protein, neuronal trafficking mediated by major kinesin-1 motor protein and microtubule (MT) dynamics via STMN2/SCG10. The screen for novel physiological JNK substrates revealed specific phosphorylation of C-terminal end of MARCKSL1 at S120, T148 and T183 both ex vivo and in vitro. By utilizing site-specific mutagenesis, various actin dynamics and migrations assays we were able to demonstrate that JNK1 phosphorylation specifically facilitates F-actin bundling and thus filament stabilisation. Consecutively, this molecular mechanism was proved to enhance formation of filopodia; cell surface projections that allow cell sensing surrounding environment and migrate efficiently. Our results visualize JNK dependent and MARCKSL1 executed induction of filopodia in neurons and fibroblast indicating general mechanism. Subsequently, inactivation of JNK action on MARCKSL1 shifts cellular actin machinery into lamellipodial dynamic arrangement. Tuning of actin cytoskeleton inevitably melds with cell migration. We observed that both active JNK and JNK pseudo-phosphorylated form of MARCKSL1 reduce actin turnover in intact cells leading to overall diminished cell motility. We demonstrate that tumour transformed cells from breast, prostate, lung and muscle-derived cancers upregulate MARCKSL1. We showed on the example of prostate cancer PC-3 cell line that JNK phosphorylation negatively controls MARCKSL1 ability to induce migration, which precedes cancer cell metastasis. The second round of identification of JNK physiological substrates resulted in detection of predominant motor protein kinesin-1 (Kif5). Mass spectrometry detailed analysis showed evident endogenous phosphorylation of kinesin-1 on S176 within motor domain that interacts with MT. In vitro phosphorylation of bacterially expressed kinesin heavy chain by JNK isoforms displayed higher specificity of JNK1 when compared to JNK3. Since, JNK1 is constitutively active in neurons it signified physiological aspect of kinesin-1 regulation. Subsequent biochemical examination revealed that kinesin-1, when not phosphorylated on JNK site, exhibits much higher affinity toward MTs. Expression of the JNK non-phosphorable kinesin-1 mutant in intact cells as well as in vitro single molecule imaging using total internal reflection fluorescence microscopy indicated that the mutant loses normal speed and is not able to move processively into proper cellular compartments. We identify novel kinesin-1 cargo protein STMN2/SCG10, which along with known kinesin-1 cargo BDNF is showing impaired trafficking when JNK activity is inhibited. Our data postulates that constitutive JNK activity in neurons is crucial for unperturbed physiologically relevant transport of kinesin-1 dependant cargo. Additionally, my work helps to validate another novel physiological JNK1 effector STMN2/SCG10 as determinant of axodendritic neurites dynamics in the developing brain through regulation of MT turnover. We show successively that this increased MT dynamics is crucial during developmental radial migration when brain layering occurs. Successively, we are able to show that introduction of JNK phosphorylation mimicking STMN2/SCG10 S62/73D mutant rescues completely JNK1 genetic deletion migration phenotype. We prove that STMN2/SCG10 is predominant JNK effector responsible for MT depolymerising activity and neurite length during brain development. Summarizing, this work describes identification of three novel JNK substrates MARCKSL1, kinesin-1 and STMN2/SCG10 and investigation of their roles in cytoskeleton dynamics and cargo transport. This data is of high importance to understand physiological meaning of JNK activity, which might have an adverse effect during pharmaceutical intervention aiming at blocking pathological JNK action.

A global transport packaging guideline for selected business areas

In this Master’s Thesis a global transport packaging guideline for selected business areas was compiled for the Fiskars the company, which provides branded consumer goods for home, garden and outdoor use. The business areas included were Home and Garden business areas. The aim of the guideline was to be a comprehensive guide for the suppliers, product development, operations and external vendors of the company. The guideline consists of written instructions, tables and illustrations that provide useful information for players working with transport packages from sourcing through to shipments. As the role of corporate responsibility and sustainability has grown, a part of responsible manufacturing strategy includes using materials that are re-usable, recyclable or recoverable as energy or through composting. Hence packaging waste management implementations of different regions were also inspected. The resulting guide covers a range of topics concerning packaging and its transport. The topics include legal requirements, restricted materials and substances, preferred materials, markings, labeling of boxes, logistics and distribution center requirements, physical testing and an inspection checklist.

Deregulation’s Impact on the Railway Freight Transport Sector’s Future in the Baltic Sea Region

The European transport market has confronted several changes during the last decade. Due to European Union legislative mandates, the railway freight market was deregulated in 2007. The market followed the trend started by other transport modes as well as other previously regulated industries such as banking, telecommunications and energy. Globally, the first country to deregulate the railway freight market was the United States, with the introduction of the Staggers Rail Act in 1980. Some European countries decided to follow suit already before regulation was mandated; among the forerunners were the United Kingdom, Sweden and Germany. The previous research has concentrated only on these countries, which has provided an interesting research gap for this thesis. The Baltic Sea Region consists of countries with different kinds of liberalization paths, including Sweden and Germany, which have been on the frontline, whereas Lithuania and Finland have only one active railway undertaking, the incumbent. The transport market of the European Union is facing further challenges in the near future, due to the Sulphur Directive, oil dependency and the changing structure of European rail networks. In order to improve the accessibility of this peripheral area, further action is required. This research focuses on topics such as the progression of deregulation, barriers to entry, country-specific features, cooperation and internationalization. Based on the research results, it can be stated that the Baltic Sea Region’s railway freight market is expected to change in the future. Further private railway undertakings are anticipated, and these would change the market structure. The realization of European Union’s plans to increase the improved rail network to cover the Baltic States is strongly hoped for, and railway freight market counterparts inside and among countries are starting to enhance their level of cooperation. The Baltic Sea Region countries have several special national characteristics which influence the market and should be taken into account when companies evaluate possible market entry actions. According to thesis interviews, the Swedish market has a strong level of cooperation in the form of an old-boy network, and is supported by a positive attitude of the incumbent towards the private railway undertakings. This has facilitated the entry process of newcomers, and currently the market has numerous operating railway undertakings. A contrary example was found from Poland, where the incumbent sent old rolling stock to the scrap yard rather than sell it to private railway undertakings. The importance of personal relations is highlighted in Russia, followed by the railway market’s strong political bond with politics. Nonetheless, some barriers to entry are shared by the Baltic Sea Region, the main ones being acquisition of rolling stock, bureaucracy and needed investments. The railway freight market is internationalizing, which is perceived via several alliances as well as the increased number of mergers and acquisitions. After deregulation, markets seem to increase the number of railway undertakings at a rather fast pace, but with the passage of time, the larger operators tend to acquire smaller ones. Therefore, it is expected that in a decade’s time, the number of railway undertakings will start to decrease in the deregulation pioneer countries, while the ones coming from behind might still experience an increase. The Russian market is expected to be totally liberalized, and further alliances between the Russian Railways and European railway undertakings are expected to occur. The Baltic Sea Region’s railway freight market is anticipated to improve, and, based on the interviewees’ comments, attract more cargoes from road to rail.

Towards optimal fractionation of lignocellulosic biomass using switchable ionic liquids

En ny familj av reversibla (switchable) joniska vätskor (SIL) innehållande 1,8-diazobicyklo-[5.4.0]-undek-7-en (DBU), en molekyl innehållande en eller flera hydroxyl- grupper (t.ex. glycerol) och en sur gas (CO2, SO2) syntetiserades via en enkel procedur samt karakteriserades. [DBU][karbonat] eller [sulfonat] bildades ur en respektive icke-jonisk blandning av en molekylär, organisk polyol (eller ennan molekyl innehållande en OH-grupp) och en amidinbas under bubblandet av en sur gas. Därtill kunde den joniska vätskan omvandlas tillbaka till sina beståndsdelar med hjälp av att upphetta och/eller bubbla en inert gas såsom kväve genom vätskan. SIL- strukturerna kartlades med bl.a. NMR- och FTIR- spektroskopi. Omvandlingen från lågpolära (molekylära) vätskor till högpolära joniska vätskor (SIL) bekräftades även genom att observera förändringar i deras fysikaliska egenskaper, såsom viskositet och färg. Nedbrytningstemperaturerna hos SILs bestämdes med hjälp av termogravimetrisk analys (TGA) som antydde att nedbrytningstemperaturen hos de syntetiserade föreningarna log mellan 50 och 200oC. De nya joniska vätskorna uppvisade högre nedbrytningstemperaturer jämfört med i litteraturen tidigare förekommande exempel och kunde därför tillämpas på flera ändamål. Därtill, reversibla (switchable) joniska vätskor uppbyggda av bl.a. alkoholer, antingen hexanol eller butanol, och CO2 samt en amidin (DBU) användes vid upplösning och fraktionering av ved. Joniska vätskor syntetiserade ur glycerol och sura gaser tillsammans med amidiner användes även för fraktionering av andra lignocellulosor såsom färsk björk (Betula pendula). Björkflis utsattes för behandling, för en period på en till fem dagar vid 100oC och under atmosfäriskt tryck. Alla syntetiserade joniska vätskor visade sig vara relativt neutrala i avseende på upplösning och avlägsnandet av lignin. Slutligen, optimala fraktioneringprocessbetingelser för ved med reversibla joniska vätskor kartlades. Fraktionering av vedbiomassa med dessa joniska vätskor uppvisade sig att vara en selektiv och effektiv metod för extraktion av olika komponenter från lignocellulosa. Den olösta fraktionen hos en vedflis, närmast cellulosa, fibrillerades. -------------------------------------------------------------------------------------------------------------------- Tässä työssä kehitettiin perhe uuden tyyppisiä, reversiibeleitä (switchable) ioninesteitä ( SIL ) joka koostuvat orgaanisesta super-emäksestä kuten 1,8- diatsabisyklo [ 5.4.0] undek- 7-eeni (DBU ) ja yhden tai useampia hydroksyyliryhmiä sisältältävästä molekyylistä (esim. glyseroli) ja happamasta kaasusta (CO2 , SO2) yksinkertaisen menetelmän avulla. [DBU] [ karbonaatti] tai [sulfonaatti] syntetisoitiin kunkin lähtöaineen seoksista kuplittamalla seosta happamalla kaasulla jolloin eksoterminen reaktio tapahtui ja ioninen neste syntyi. Ioniset nesteet voitiin palauttaa takaisin lähtöaineseokseksi kuumentamalla ja/tai kuplittamalla neutraalia kaasua (esim. typpi) seoksen läpi. SIL rakenteet määritettiin ja niiden ominaisuudet kartoitettiin eri menetelmillä, mukaan lukien NMR- ja FTIR -spektroskopia. Ionisen, korkeapoläärisen nesteen syntyminen todennettiin myös viskositeettimittauksilla ja värinmuutoksilla käyttäen hyväksi polariteetti-indikaattoria (Nile red). Myös hajoamislämpötilat määritettiin termogravimetrisellä analyysillä (TGA) ja todettiin että syntetisoitujen yhdisteiden hajoamislämpötila oli välillä 50 ja 200oC . Näiden uusien reversiibeleiden ioninesteiden hajoamisämpötilat olivat korkeammat verrattuna kirjallisuudessa aikaisemmin mainittuihin esimerkkeihin joten niitä voidaan soveltaa useisiin tarkoituksiin. Myös ioninesteitä jotka sisälsivät primäärejä alkoholeja rakennusaineina syntetisoitiin ja hyödynnettiin puun fraktioinnissa. Männyn ja kuusen lisäksi tuoreita koivulastuja onnistuttiin fraktioimaan miedoissa olosuhteissa. Kaikkien syntetisoitujen ioninesteiden todettiin olevan suhteellisen neutraaleja ligniinin liuotuksen suhteen. Vielä, optimaaliset fraktiointiolosuhteet määritettiin ryhmälle reversiibeleitä ioninesteitä ja näiden uudenlaisten ioninesteiden todettiin olevan tehokkaita puun ja muiden lignoselluloosien eri fraktioiden liuotuksessa. Liukenematon osa puulastua joka oli lähinnä selluloosaa fibrilloitui.

State of logistics and transport in the Baltic Sea region in 2025

The world’s pace of change is accelerating and new innovations, inventions and technologies come about every day. Change is unavoidable. It is difficult to keep up and even more difficult to prepare for the future. Even though it is not possible to know exactly what will happen in the future, by studying futures people can better anticipate what might lie ahead. By making decisions and realizing the consequences of their choices today, people and governments are able to actively decide how they will act in the future. Both opportunities and pitfalls lie ahead, which encourages actors to make more farsighted decisions. The Baltic Sea region is an interesting area for futures studies. It comprises 11 nations and more than 100 million inhabitants and entails countries with advanced, high-income economies, like Finland, Germany and Denmark, and developing economies, like Russia, Latvia and Lithuania. The western, eastern, northern and southern parts of the region are separated by the Baltic Sea, which at the same time represents a barrier and a facility for trade and travel between the countries belonging to the region The purpose of this study was to uncover the most probable future of transport and logistics in the Baltic Sea region in 2025 by using the Delphi method. Altogether 109 responses were collected in two separate instances from experts in all the Baltic Sea region countries, 56 of whom were defined as academic respondents and 53 of whom business respondents. Only minor differences in the opinions of academic and business experts were discovered, and the larger differences lie between eastern and western response groups. The Baltic Sea region is a very heterogeneous region and the division is clearest between East and West, which differ in political, economic, social, technological and environmental aspects. The probable future of the Baltic Sea region presented in this study is coherent with previous studies on the same subject. The future of the Baltic Sea region in terms of logistics and transport looks quite bright according to the experts who participated in the study. Trade volumes will grow and the importance of logistics and transport to the competitiveness of the region will increase. Respondents from eastern countries seemed to be more optimistic about the future in general. Most differences between opinions could be explained by the gap in technological and infrastructural development between the East and West. As eastern countries are less-developed in some parts of their economies, it is easier for them to improve the technical condition of infrastructure by merely catching up with the western countries.

Ionic liquid mediated biomass deconstruction: from analysis challenges to fermentable sugars

Ionic liquids, ILs, have recently been studied with accelerating interest to be used for a deconstruction/fractionation, dissolution or pretreatment processing method of lignocellulosic biomass. ILs are usually utilized combined with heat. Regarding lignocellulosic recalcitrance toward fractionation and IL utilization, most of the studies concern IL utilization in the biomass fermentation process prior to the enzymatic hydrolysis step. It has been demonstrated that IL-pretreatment gives more efficient hydrolysis of the biomass polysaccharides than enzymatic hydrolysis alone. Both cellulose (especially cellulose) and lignin are very resistant towards fractionation and even dissolution methods. As an example, it can be mentioned that softwood, hardwood and grass-type plant species have different types of lignin structures leading to the fact that softwood lignin (guaiacyl lignin dominates) is the most difficult to solubilize or chemically disrupt. In addition to the known conventional biomass processing methods, several ILs have also been found to efficiently dissolve either cellulose and/or wood samples – different ILs are suitable for different purposes. An IL treatment of wood usually results in non-fibrous pulp, where lignin is not efficiently separated and wood components are selectively precipitated, as cellulose is not soluble or degradable in ionic liquids under mild conditions. Nevertheless, new ILs capable of rather good fractionation performance have recently emerged. The capability of the IL to dissolve or deconstruct wood or cellulose depends on several factors, (e.g. sample origin, the particle size of the biomass, mechanical treatments as pulverization, initial biomassto-IL ratio, water content of the biomass, possible impurities of IL, reaction conditions, temperature etc). The aim of this study was to obtain (fermentable) saccharides and other valuable chemicals from wood by a combined heat and IL-treatment. Thermal treatments alone contribute to the degradation of polysaccharides (e.g. 150 °C alone is said to cause the degradation of polysaccharides), thus temperatures below that should be used, if the research interest lies on the IL effectiveness. On the other hand, the efficiency of the IL-treatment can also be enhanced to combine other treatment methods, (e.g. microwave heating). The samples of spruce, pine and birch sawdust were treated with either 1-Ethyl-3-methylimidazolium chloride, Emim Cl, or 1-Ethyl-3-methylimidazolium acetate, Emim Ac, (or with ionized water for comparison) at various temperatures (where focus was between 80 and 120 °C). The samples were withdrawn at fixed time intervals (the main interest treatment time area lied between 0 and 100 hours). Double experiments were executed. The selected mono- and disaccharides, as well as their known degradation products, 5-hydroxymethylfurfural, 5-HMF, and furfural were analyzed with capillary electrophoresis, CE, and high-performance liquid chromatography, HPLC. Initially, even GC and GC-MS were utilized. Galactose, glucose, mannose and xylose were the main monosaccharides that were present in the wood samples exposed to ILs at elevated temperatures; in addition, furfural and 5-HMF were detected; moreover, the quantitative amount of the two latter ones were naturally increasing in line with the heating time or the IL:wood ratio.

Catalytic upgrading of biomass extractives to fine chemicals over supported ionic liquid catalysts (SILCAs)

Behovet av förnyelsebar energi ökar ständigt eftersom det finns en strävan att minska beroendet av fossila bränslen. Dessutom är tillgångar av fossila bränslen begränsade. Miljövänliga processer för bioraffinaderier erbjuder en stor möjlighet för produktion av energi, bränslen och kemikalier. Den finska och svenska skogsindustrin har en lång tradition i utnyttjandet av skogsbiomassor. Bioraffinaderier som integreras med pappers- och cellulosaindustrin kan frambringa både ekonomiska och ekologiska fördelar i framställning av traditionella och biobaserade produkter. I doktorsarbetet studerades omvandling av extraktivämnen till finkemikalier som kan användas t.ex. av läkemedelsindustrin. Extraktivämnen fås ur biomassa. I forskningsarbetet framställdes biobaserade finkemikalier med hjälp av katalysatorer som baserar sig på joniska vätskor. Biomassan består av cellulosa, hemicellulosa, lignin och extraktivämnen, vilka huvudsakligen är terpener, vaxer och fettsyror. Extraktivämen är vedens komponenter, som kan separeras ur vedmaterialet med hjälp av neutrala lösningsmedel. Joniska vätskekatalysatorer som var immobiliserade på fasta bärare utnyttjades för isomerisering av α,β-pinenoxider samt hydrogenering citral. Inverkan av joniska vätskor på katalysatorns aktivitet och reaktionernas produktfördelning undersöktes under varierande reaktionsbetingelser. Kinetiska modeller för pinenoxidens isomeriseringsreaktioner beskrev väl experimentellt upptäckta skillnader mellan olika katalysatorer. --------------------------------------------------- Uusiutuvan energian tarve on kasvussa, koska riippuvuutta fossiilisista polttoaineista pyritään vähentämään. Tämän lisäksi fossiilisten polttoaineiden varannot ovat rajalliset. Ympäristöystävälliset biojalostusprosessit ovat näin ollen suuri mahdollisuus energian, polttoaineiden ja kemikaalien tuotannossa. Suomen ja Ruotsin metsäteollisuudella on pitkät perinteet metsäbiomassojen hyödyntämisessä. Paperi- ja selluteollisuuden yhteyteen integroiduilla biojalostamoilla voidaan luoda taloudellisia ja ympäristöllisiä etuja sekä perinteisten että biopohjaisten tuotteiden valmistuksessa. Väitöstyössä on tutkittu biomassan uuteaineiden kemiallista muuntamista hienokemikaaleiksi, joita voidaan käyttää esimerkiksi lääkeaineteollisuudessa. Biopohjaisia hienokemikaaleja on valmistettu biomassan uuteaineista ionisiin nesteisiin perustuvilla katalyyteillä. Biomassa koostuu selluloosasta, hemiselluloosasta, ligniinistä sekä uuteaineista, jotka ovat pääosin terpeenejä, vahoja tai rasvahappoja. Uuteaineet ovat puun komponentteja, jotka voidaan erottaa puusta neutraalien liuottimien avulla. Kiinteän kantajan päälle immobilisoituja ionisia nestekatalyyttejä (Supported Ionic Liquid Catalyst) hyödynnettiin α,β-pineenioksidien isomerisointireaktioissa sekä sitraalin vedytysreaktioissa. Ionisten nesteiden vaikutusta katalyyttien aktiivisuuteen sekä reaktioiden tuotejakaumaan tutkittiin erilaisissa reaktio-olosuhteissa. Pineenioksidien isomerisointireaktioiden kineettiset mallit kuvasivat hyvin kokeellisesti todettuja katalyyttien eroavaisuuksia.

Effect of collection, transport, processing and storage of blood specimens on the activity of lysosomal enzymes in plasma and leukocytes

This study was designed to evaluate the effect of different conditions of collection, transport and storage on the quality of blood samples from normal individuals in terms of the activity of the enzymes ß-glucuronidase, total hexosaminidase, hexosaminidase A, arylsulfatase A and ß-galactosidase. The enzyme activities were not affected by the different materials used for collection (plastic syringes or vacuum glass tubes). In the evaluation of different heparin concentrations (10% heparin, 5% heparin, and heparinized syringe) in the syringes, it was observed that higher doses resulted in an increase of at least 1-fold in the activities of ß-galactosidase, total hexosaminidase and hexosaminidase A in leukocytes, and ß-glucuronidase in plasma. When the effects of time and means of transportation were studied, samples that had been kept at room temperature showed higher deterioration with time (72 and 96 h) before processing, and in this case it was impossible to isolate leukocytes from most samples. Comparison of heparin and acid citrate-dextrose (ACD) as anticoagulants revealed that ß-glucuronidase and hexosaminidase activities in plasma reached levels near the lower normal limits when ACD was used. In conclusion, we observed that heparin should be used as the preferable anticoagulant when measuring these lysosomal enzyme activities, and we recommend that, when transport time is more than 24 h, samples should be shipped by air in a styrofoam box containing wet ice.

Skin secretion of Siphonops paulensis (Gymnophiona, Amphibia) forms voltage-dependent ionic channels in lipid membranes

The effect of the skin secretion of the amphibian Siphonops paulensis was investigated by monitoring the changes in conductance of an artificial planar lipid bilayer. Skin secretion was obtained by exposure of the animals to ether-saturated air, and then rinsing the animals with distilled water. Artificial lipid bilayers were obtained by spreading a solution of azolectin over an aperture of a Delrin cup inserted into a cut-away polyvinyl chloride block. In 9 of 12 experiments, the addition of the skin secretion to lipid bilayers displayed voltage-dependent channels with average unitary conductance of 258 ± 41.67 pS, rather than nonspecific changes in bilayer conductance. These channels were not sensitive to 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid or tetraethylammonium ion, but the experimental protocol used does not permit us to specify their characteristics.

Ionic radiocontrast inhibits endothelium-dependent vasodilation of the canine renal artery in vitro: possible mechanism of renal failure following contrast medium infusion

To determine if radiocontrast impairs vascular relaxation of the renal artery, segments (4-5 mm in length) of canine renal artery were suspended in vitro in organ chambers to measure isometric force (95% O2/5% CO2, at 37ºC). Arterial segments with and without endothelium were placed at the optimal point of their length-tension relation and incubated with 10 µM indomethacin to prevent synthesis of endogenous prostanoids. The presence of nonionic radiocontrast (iohexol, Omnipaque 350, 1 ml in 25 ml control solution, 4% (v/v)) did not alter endothelium-dependent relaxation to acetylcholine in rings precontracted with both norepinephrine and prostaglandin F2alpha (N = 6). When the rings were precontracted with prostaglandin F2alpha, the presence of ionic contrast did not inhibit the relaxation of the arteries. However, in canine renal arteries contracted with norepinephrine, the presence of ionic radiocontrast (diatrizoate meglumine and diatrizoate sodium, MD-76, 1 ml in 25 ml control solution, 4% (v/v)) inhibited relaxation in response to acetylcholine, sodium nitroprusside (N = 6 in each group), and isoproterenol (N = 5; P < 0.05). Rings were relaxed less than 50% of norepinephrine contraction. Following removal of the contrast, vascular relaxation in response to the agonists returned to normal. These results indicate that ionic radiocontrast nonspecifically inhibits vasodilation (both cAMP-mediated and cGMP-mediated) of canine renal arteries contracted with norepinephrine. This reversible impairment of vasodilation could inhibit normal renal perfusion and act as a mechanism of renal failure following radiocontrast infusion. In the adopted experimental protocol the isoproterenol-induced relaxation of renal arteries precontracted with norepinephrine was more affected, suggesting a pivotal role of the cAMP system.

Mitochondrial K+ transport and cardiac protection during ischemia/reperfusion

Mitochondrial ion transport, oxidative phosphorylation, redox balance, and physical integrity are key factors in tissue survival following potentially damaging conditions such as ischemia/reperfusion. Recent research has demonstrated that pharmacologically activated inner mitochondrial membrane ATP-sensitive K+ channels (mitoK ATP) are strongly cardioprotective under these conditions. Furthermore, mitoK ATP are physiologically activated during ischemic preconditioning, a procedure which protects against ischemic damage. In this review, we discuss mechanisms by which mitoK ATP may be activated during preconditioning and the mitochondrial and cellular consequences of this activation, focusing on end-effects which may promote ischemic protection. These effects include decreased loss of tissue ATP through reverse activity of ATP synthase due to increased mitochondrial matrix volumes and lower transport of adenine nucleotides into the matrix. MitoK ATP also decreases the release of mitochondrial reactive oxygen species by promoting mild uncoupling in concert with K+/H+ exchange. Finally, mitoK ATP activity may inhibit mitochondrial Ca2+ uptake during ischemia, which, together with decreased reactive oxygen release, can prevent mitochondrial permeability transition, loss of organelle function, and loss of physical integrity. We discuss how mitochondrial redox status, K+ transport, Ca2+ transport, and permeability transitions are interrelated during ischemia/reperfusion and are determinant factors regarding the extent of tissue damage.