Hepatic damage during acute pancreatitis in the rat

We studied the alterations in the metabolism of liver mitochondria in rats with acute pancreatitis. Male Wistar rats were allocated to a control group (group I) and to five other groups corresponding to 2, 4, 12, 24 and 48 h after the induction of acute pancreatitis by the injection of 5% sodium taurocholate into the pancreatic duct. Sham-operated animals were submitted to the same surgical steps except for the induction of acute pancreatitis. Mitochondrial oxidation and phosphorylation were measured polarographically by determining oxygen consumption without ADP (basal respiration, state 4) and in the presence of ADP (activated respiration, state 3). Serum amylase, transaminases (ALT and AST) and protein were also determined. Ascitic fluid, contents of amylase, trypsin and total protein were also determined and arterial blood pressure was measured in all groups. In ascitic fluid, trypsin and amylase increased reaching a maximum at 2 and 4 h, respectively. Serum amylase increased at 2 h reaching a maximum at 4 h. Serum transaminase levels increased at 12 and 24 h. After 2 h (and also 4 h) there was an increase in state 4 respiration (45.65 ± 1.79 vs 28.96 ± 1.50) and a decrease in respiration control rate (3.53 ± 0.09 vs 4.45 ± 0.08) and in the ADP/O ratio (1.77 ± 0.02 vs 1.91 ± 0.01) compared to controls (P<0.05). These results indicate a disruption of mitochondrial function, which recovered after 12 h. In the 48-h groups there was mitochondrial damage similar to that occurring in ischemic lesion. Beat-to-beat analysis (30 min) showed that arterial blood pressure remained normal up to 24 h (111 ± 3 mmHg) while a significant decrease occurred in the 48-h group (91 ± 4 mmHg). These data suggest biphasic damage in mitochondrial function in acute pancreatitis: an initial uncoupled phase, possibly secondary to enzyme activity, followed by a temporary recovery and then a late and final dysfunction, associated with arterial hypotension, possibly related to ischemic damage.

Testing FCM technique for the wind energy scenarios in Finland

In the latter days, human activities constantly increase greenhouse gases emissions in the atmosphere, which has a direct impact on a global climate warming. Finland as European Union member, developed national structural plan to promote renewable energy generation, pursuing the aspects of Directive 2009/28/EC and put it on the sharepoint. Finland is on a way of enhancing national security of energy supply, increasing diversity of the energy mix. There are plenty significant objectives to develop onshore and offshore wind energy generation in country for a next few decades, as well as another renewable energy sources. To predict the future changes, there are a lot of scenario methods developed and adapted to energy industry. The Master’s thesis explored “Fuzzy cognitive maps” approach in scenarios developing, which captures expert’s knowledge in a graphical manner and using these captures for a raw scenarios testing and refinement. There were prospects of Finnish wind energy development for the year of 2030 considered, with aid of FCM technique. Five positive raw scenarios were developed and three of them tested against integrated expert’s map of knowledge, using graphical simulation. The study provides robust scenarios out of the preliminary defined, as outcome, assuming the impact of results, taken after simulation. The thesis was conducted in such way, that there will be possibilities to use existing knowledge captures from expert panel, to test and deploy different sets of scenarios regarding to Finnish wind energy development.

Interrelationship between adipocytes and fibroblasts during acute damage to the subcutaneous adipose tissue of rats: an ultrastructural study

Ultrastructural phenotypic transitional features were noted between adult adipocytes and fibroblasts in the subcutaneous adipose tissue of the dorsal pad of normal adult Wistar rats of both sexes, weighing 180-260 g, after acute injury either by the implantation of small (1.8 x 1 x 0.4 cm) perforated plastic boxes or by local heat application. Soon after the inflicted damage, fat-containing cells presented variable shapes. Early after damage, some of these cells were round, adipocyte-like, with numerous and large cytoplasmic fat droplets. A few days later, fat-containing cells became elongated, with the fat droplets in their cytoplasm becoming smaller and less numerous. The cells also showed a prominent active rough endoplasmic reticulum and newly formed collagenous matrix accumulated in the interstices. Although current views consider adult adipocytes to be terminal cells, the present findings, in their time sequence, strongly suggest the transformation of adipocytes into fibroblasts after acute injury to adipose tissue.

Liquid cooling solutions for rotating permanent magnet synchronous machines

In the design of electrical machines, efficiency improvements have become very important. However, there are at least two significant cases in which the compactness of electrical machines is critical and the tolerance of extremely high losses is valued: vehicle traction, where very high torque density is desired at least temporarily; and direct-drive wind turbine generators, whose mass should be acceptably low. As ever higher torque density and ever more compact electrical machines are developed for these purposes, thermal issues, i.e. avoidance of over-temperatures and damage in conditions of high heat losses, are becoming of utmost importance. The excessive temperatures of critical machine components, such as insulation and permanent magnets, easily cause failures of the whole electrical equipment. In electrical machines with excitation systems based on permanent magnets, special attention must be paid to the rotor temperature because of the temperature-sensitive properties of permanent magnets. The allowable temperature of NdFeB magnets is usually significantly less than 150 ˚C. The practical problem is that the part of the machine where the permanent magnets are located should stay cooler than the copper windings, which can easily tolerate temperatures of 155 ˚C or 180 ˚C. Therefore, new cooling solutions should be developed in order to cool permanent magnet electrical machines with high torque density and because of it with high concentrated losses in stators. In this doctoral dissertation, direct and indirect liquid cooling techniques for permanent magnet synchronous electrical machines (PMSM) with high torque density are presented and discussed. The aim of this research is to analyse thermal behaviours of the machines using the most applicable and accurate thermal analysis methods and to propose new, practical machine designs based on these analyses. The Computational Fluid Dynamics (CFD) thermal simulations of the heat transfer inside the machines and lumped parameter thermal network (LPTN) simulations both presented herein are used for the analyses. Detailed descriptions of the simulated thermal models are also presented. Most of the theoretical considerations and simulations have been verified via experimental measurements on a copper tooth-coil (motorette) and on various prototypes of electrical machines. The indirect liquid cooling systems of a 100 kW axial flux (AF) PMSM and a 110 kW radial flux (RF) PMSM are analysed here by means of simplified 3D CFD conjugate thermal models of the parts of both machines. In terms of results, a significant temperature drop of 40 ̊C in the stator winding and 28 ̊C in the rotor of the AF PMSM was achieved with the addition of highly thermally conductive materials into the machine: copper bars inserted in the teeth, and potting material around the end windings. In the RF PMSM, the potting material resulted in a temperature decrease of 6 ̊C in the stator winding, and in a decrease of 10 ̊C in the rotor embedded-permanentmagnets. Two types of unique direct liquid cooling systems for low power machines are analysed herein to demonstrate the effectiveness of the cooling systems in conditions of highly concentrated heat losses. LPTN analysis and CFD thermal analysis (the latter being particularly useful for unique design) were applied to simulate the temperature distribution within the machine models. Oil-immersion cooling provided good cooling capability for a 26.6 kW PMSM of a hybrid vehicle. A direct liquid cooling system for the copper winding with inner stainless steel tubes was designed for an 8 MW directdrive PM synchronous generator. The design principles of this cooling solution are described in detail in this thesis. The thermal analyses demonstrate that the stator winding and the rotor magnet temperatures are kept significantly below their critical temperatures with demineralized water flow. A comparison study of the coolant agents indicates that propylene glycol is more effective than ethylene glycol in arctic conditions.

Photodynamic DNA damage induced by phycocyanin and its repair in Saccharomyces cerevisiae

In the present study, we analyzed DNA damage induced by phycocyanin (PHY) in the presence of visible light (VL) using a set of repair endonucleases purified from Escherichia coli. We demonstrated that the profile of DNA damage induced by PHY is clearly different from that induced by molecules that exert deleterious effects on DNA involving solely singlet oxygen as reactive species. Most of PHY-induced lesions are single strand breaks and, to a lesser extent, base oxidized sites, which are recognized by Nth, Nfo and Fpg enzymes. High pressure liquid chromatography coupled to electrochemical detection revealed that PHY photosensitization did not induce 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) at detectable levels. DNA repair after PHY photosensitization was also investigated. Plasmid DNA damaged by PHY photosensitization was used to transform a series of Saccharomyces cerevisiae DNA repair mutants. The results revealed that plasmid survival was greatly reduced in rad14 mutants, while the ogg1 mutation did not modify the plasmid survival when compared to that in the wild type. Furthermore, plasmid survival in the ogg1 rad14 double mutant was not different from that in the rad14 single mutant. The results reported here indicate that lethal lesions induced by PHY plus VL are repaired differently by prokaryotic and eukaryotic cells. Morever, nucleotide excision repair seems to play a major role in the recognition and repair of these lesions in Saccharomyces cerevisiae.

Vibrations in Rotating Machinery Arising from Minor Imperfections in Component Geometries

Vibrations in machines can cause noise, decrease the performance, or even damage the machine. Vibrations appear if there is a source of vibration that excites the system. In the worst case scenario, the excitation frequency coincides with the natural frequency of the machine causing resonance. Rotating machines are a machine type, where the excitation arises from the machine itself. The excitation originates from the mass imbalance in the rotating shaft, which always exists in machines that are manufactured using conventional methods. The excitation has a frequency that is dependent on the rotational speed of the machine. The rotating machines in industrial use are usually designed to rotate at a constant rotational speed, the case where the resonances can be easily avoided. However, the machines that have a varying operational speed are more problematic due to a wider range of frequencies that have to be avoided. Vibrations, which frequencies equal to rotational speed frequency of the machine are widely studied and considered in the typical machine design process. This study concentrates on vibrations, which arise from the excitations having frequencies that are multiples of the rotational speed frequency. These vibrations take place when there are two or more excitation components in a revolution of a rotating shaft. The dissertation introduces four studies where three kinds of machines are experiencing vibrations caused by different excitations. The first studied case is a directly driven permanent magnet generator used in a wind power plant. The electromagnetic properties of the generator cause harmonic excitations in the system. The dynamic responses of the generator are studied using the multibody dynamics formulation. In another study, the finite element method is used to study the vibrations of a magnetic gear due to excitations, which frequencies equal to the rotational speed frequency. The objective is to study the effects of manufacturing and assembling inaccuracies. Particularly, the eccentricity of the rotating part with respect to non-rotating part is studied since the eccentric operation causes a force component in the direction of the shortest air gap. The third machine type is a tube roll of a paper machine, which is studied while the tube roll is supported using two different structures. These cases are studied using different formulations. In the first case, the tube roll is supported by spherical roller bearings, which have some wavinesses on the rolling surfaces. Wavinesses cause excitations to the tube roll, which starts to resonate at the frequency that is a half of the first natural frequency. The frequency is in the range where the machine normally operates. The tube roll is modeled using the finite element method and the bearings are modeled as nonlinear forces between the tube roll and the pedestals. In the second case studied, the tube roll is supported by freely rotating discs, which wavinesses are also measured. The above described phenomenon is captured as well in this case, but the simulation methodology is based on the flexible multibody dynamics formulation. The simulation models that are used in both of the last two cases studied are verified by measuring the actual devices and comparing the simulated and measured results. The results show good agreement.

Magnesium chloride alone or in combination with diazepam fails to prevent hippocampal damage following transient forebrain ischemia

In the central nervous system, magnesium ion (Mg2+) acts as an endogenous modulator of N-methyl-D-aspartate (NMDA)-coupled calcium channels, and may play a major role in the pathomechanisms of ischemic brain damage. In the present study, we investigated the effects of magnesium chloride (MgCl2, 2.5, 5.0 or 7.5 mmol/kg), either alone or in combination with diazepam (DZ), on ischemia-induced hippocampal cell death. Male Wistar rats (250-300 g) were subjected to transient forebrain ischemia for 15 min using the 4-vessel occlusion model. MgCl2 was applied systemically (sc) in single (1x, 2 h post-ischemia) or multiple doses (4x, 1, 2, 24 and 48 h post-ischemia). DZ was always given twice, at 1 and 2 h post-ischemia. Thus, ischemia-subjected rats were assigned to one of the following treatments: vehicle (0.1 ml/kg, N = 34), DZ (10 mg/kg, N = 24), MgCl2 (2.5 mmol/kg, N = 10), MgCl2 (5.0 mmol/kg, N = 17), MgCl2 (7.5 mmol/kg, N = 9) or MgCl2 (5 mmol/kg) + DZ (10 mg/kg, N = 14). Seven days after ischemia the brains were analyzed histologically. Fifteen minutes of ischemia caused massive pyramidal cell loss in the subiculum (90.3%) and CA1 (88.4%) sectors of the hippocampus (P<0.0001, vehicle vs sham). Compared to the vehicle-treated group, all pharmacological treatments failed to attenuate the ischemia-induced death of both subiculum (lesion: 86.7-93.4%) and CA1 (lesion: 85.5-91.2%) pyramidal cells (P>0.05). Both DZ alone and DZ + MgCl2 reduced rectal temperature significantly (P<0.05). No animal death was observed after drug treatment. These data indicate that exogenous magnesium, when administered systemically post-ischemia even in different multiple dose schedules, alone or with diazepam, is not useful against the histopathological effects of transient global cerebral ischemia in rats.

Ischemic preconditioning reduces peripheral oxidative damage associated with brain ischemia in rats

Brain ischemia followed by reperfusion causes neuronal death related to oxidative damage. Furthermore, it has been reported that subjects suffering from ischemic cerebrovascular disorders exhibit changes in circulating platelet aggregation, a characteristic that might be important for their clinical outcome. In the present investigation we studied tert-butyl hydroperoxide-initiated plasma chemiluminescence and thiol content as measures of peripheral oxidative damage in naive and preconditioned rats submitted to forebrain ischemia produced by the 4-vessel occlusion method. Rats were submitted to 2 or 10 min of global transient forebrain ischemia followed by 60 min or 1, 2, 5, 10 or 30 days of reperfusion. Preconditioned rats were submitted to a 10-min ischemic episode 1 day after a 2-min ischemic event (2 + 10 min), followed by 60 min or 1 or 2 days of reperfusion. It has been demonstrated that such preconditioning protects against neuronal death in rats and gerbils submitted to a lethal (10 min) ischemic episode. The results show that both 2 and 10 min of ischemia cause an increase of plasma chemiluminescence when compared to control and sham rats. In the 2-min ischemic group, the effect was not present after reperfusion. In the 10-min ischemic group, the increase was present up to 1 day after recirculation and values returned to control levels after 2 days. However, rats preconditioned to ischemia (2 + 10 min) and reperfusion showed no differences in plasma chemiluminescence when compared to controls. We also analyzed plasma thiol content since it has been described that sulfhydryl (SH) groups significantly contribute to the antioxidant capacity of plasma. There was a significant decrease of plasma thiol content after 2, 10 and 2 + 10 min of ischemia followed by reperfusion when compared to controls. We conclude that ischemia may cause, along with brain oxidative damage and cell death, a peripheral oxidative damage that is reduced by the preconditioning phenomenon.

Ghost protein damage by peroxynitrite and its protection by melatonin

We have studied the effect of peroxynitrite (ONOO-) on the membrane cytoskeleton of red blood cells and its protection by melatonin. Analysis of the protein fraction of the preparation by SDS-PAGE revealed a dose-dependent (0-600 µM ONOO-) disappearance at pH 7.4 of the main proteins: spectrin, band 3, and actin, with the concomitant formation of high-molecular weight aggregates resistant to reduction by ß-mercaptoethanol (2%) at room temperature for 20 min. These aggregates were not solubilized by 8 M urea. Incubation of the membrane cytoskeleton with ONOO- was characterized by a marked depletion of free sulfhydryl groups (50% at 250 µM ONOO-). However, a lack of effect of ß-mercaptoethanol suggests that, under our conditions, aggregate formation is not mediated only by sulfhydryl oxidation. The lack of a protective effect of the metal chelator diethylenetriaminepentaacetic acid confirmed that ONOO--induced oxidative damage does not occur only by a transition metal-dependent mechanism. However, we demonstrated a strong protection against cytoskeletal alterations by desferrioxamine, which has been described as a direct scavenger of the protonated form of peroxynitrite. Desferrioxamine (0.5 mM) also inhibited the loss of tryptophan fluorescence observed when the ghosts were treated with ONOO-. Glutathione, cysteine, and Trolox® (1 mM), but not mannitol (100 mM), were able to protect the proteins against the effect of ONOO- in a dose-dependent manner. Melatonin (0-1 mM) was especially efficient in reducing the loss of spectrin proteins when treated with ONOO- (90% at 500 µM melatonin). Our findings show that the cytoskeleton, and in particular spectrin, is a sensitive target for ONOO-. Specific antioxidants can protect against such alterations, which could seriously impair cell dynamics and generate morphological changes.

Simulation of wind powered hydraulic heating system

The objective of this master’s thesis was to design and simulate a wind powered hydraulic heating system that can operate independently in remote places where the use of electricity is not possible. Components for the system were to be selected in such a way that the conditions for manufacture, use and economic viability are the as good as possible. Savonius rotor was chosen for wind turbine, due to its low cut in speed and robust design. Savonius rotor produces kinetic energy in wide wind speed range and it can withstand high wind gusts. Radial piston pump was chosen for the flow source of the hydraulic heater. Pump type was selected due to its characteristics in low rotation speeds and high efficiency. Volume flow from the pump is passed through the throttle orifice. Pressure drop over the orifice causes the hydraulic oil to heat up and, thus, creating thermal energy. Thermal energy in the oil is led to radiator where it conducts heat to the environment. The hydraulic heating system was simulated. For this purpose a mathematical models of chosen components were created. In simulation wind data gathered by Finnish meteorological institute for 167 hours was used as input. The highest produced power was achieved by changing the orifice diameter so that the rotor tip speed ratio follows the power curve. This is not possible to achieve without using electricity. Thus, for the orifice diameter only one, the optimal value was defined. Results from the simulation were compared with investment calculations. Different parameters effecting the investment profitability were altered in sensitivity analyses in order to define the points of investment profitability. Investment was found to be profitable only with high average wind speeds.

Evaluation of radioinduced damage and repair capacity in blood lymphocytes of breast cancer patients

Genetic damage caused by ionizing radiation and repair capacity of blood lymphocytes from 3 breast cancer patients and 3 healthy donors were investigated using the comet assay. The comets were analyzed by two parameters: comet tail length and visual classification. Blood samples from the donors were irradiated in vitro with a 60Co source at a dose rate of 0.722 Gy/min, with a dose range of 0.2 to 4.0 Gy and analyzed immediately after the procedure and 3 and 24 h later. The basal level of damage and the radioinduced damage were higher in lymphocytes from breast cancer patients than in lymphocytes from healthy donors. The radioinduced damage showed that the two groups had a similar response when analyzed immediately after the irradiations. Therefore, while the healthy donors presented a considerable reduction of damage after 3 h, the patients had a higher residual damage even 24 h after exposure. The repair capacity of blood lymphocytes from the patients was slower than that of lymphocytes from healthy donors. The possible influence of age, disease stage and mutations in the BRCA1 and BRCA2 genes are discussed. Both parameters adopted proved to be sensitive and reproducible: the dose-response curves for DNA migration can be used not only for the analysis of cellular response but also for monitoring therapeutic interventions. Lymphocytes from the breast cancer patients presented an initial radiosensitivity similar to that of healthy subjects but a deficient repair mechanism made them more vulnerable to the genotoxic action of ionizing radiation. However, since lymphocytes from only 3 patients and 3 normal subjects were analyzed in the present paper, additional donors will be necessary for a more accurate evaluation.

The decrease in uroporphyrinogen decarboxylase activity induced by ethanol predisposes rats to the development of porphyria and accelerates xenobiotic-triggered porphyria, regardless of hepatic damage

We evaluated the porphyrinogenic ability of ethanol (20% in drinking water) per se, its effect on the development of sporadic porphyria cutanea tarda induced by hexachlorobenzene in female Wistar rats (170-190 g, N = 8/group), and the relationship with hepatic damage. Twenty-five percent of the animals receiving ethanol increased up to 14-, 25-, and 4.5-fold the urinary excretion of delta-aminolevulinate, porphobilinogen, and porphyrins, respectively. Ethanol exacerbated the precursor excretions elicited by hexachlorobenzene. Hepatic porphyrin levels increased by hexachlorobenzene treatment, while this parameter only increased (up to 90-fold) in some of the animals that received ethanol alone. Ethanol reduced the activities of uroporphyrinogen decarboxylase, delta-aminolevulinate dehydrase and ferrochelatase. In the ethanol group, many of the animals showed a 30% decrease in uroporphyrinogen activity; in the ethanol + hexachlorobenzene group, this decrease occurred before the one caused by hexachlorobenzene alone. Ethanol exacerbated the effects of hexachlorobenzene, among others, on the rate-limiting enzyme delta-aminolevulinate synthetase. The plasma activities of enzymes that are markers of hepatic damage were similar in all drug-treated groups. These results indicate that 1) ethanol exacerbates the biochemical manifestation of sporadic hexachlorobenzene-induced porphyria cutanea tarda; 2) ethanol per se affects several enzymatic and excretion parameters of the heme metabolic pathway; 3) since not all the animals were affected to the same extent, ethanol seems to be a porphyrinogenic agent only when there is a predisposition, and 4) hepatic damage showed no correlation with the development of porphyria cutanea tarda.

Large-eddy simulation of wind flows over complex terrains for wind energy applications

Wind energy has obtained outstanding expectations due to risks of global warming and nuclear energy production plant accidents. Nowadays, wind farms are often constructed in areas of complex terrain. A potential wind farm location must have the site thoroughly surveyed and the wind climatology analyzed before installing any hardware. Therefore, modeling of Atmospheric Boundary Layer (ABL) flows over complex terrains containing, e.g. hills, forest, and lakes is of great interest in wind energy applications, as it can help in locating and optimizing the wind farms. Numerical modeling of wind flows using Computational Fluid Dynamics (CFD) has become a popular technique during the last few decades. Due to the inherent flow variability and large-scale unsteadiness typical in ABL flows in general and especially over complex terrains, the flow can be difficult to be predicted accurately enough by using the Reynolds-Averaged Navier-Stokes equations (RANS). Large- Eddy Simulation (LES) resolves the largest and thus most important turbulent eddies and models only the small-scale motions which are more universal than the large eddies and thus easier to model. Therefore, LES is expected to be more suitable for this kind of simulations although it is computationally more expensive than the RANS approach. With the fast development of computers and open-source CFD software during the recent years, the application of LES toward atmospheric flow is becoming increasingly common nowadays. The aim of the work is to simulate atmospheric flows over realistic and complex terrains by means of LES. Evaluation of potential in-land wind park locations will be the main application for these simulations. Development of the LES methodology to simulate the atmospheric flows over realistic terrains is reported in the thesis. The work also aims at validating the LES methodology at a real scale. In the thesis, LES are carried out for flow problems ranging from basic channel flows to real atmospheric flows over one of the most recent real-life complex terrain problems, the Bolund hill. All the simulations reported in the thesis are carried out using a new OpenFOAM® -based LES solver. The solver uses the 4th order time-accurate Runge-Kutta scheme and a fractional step method. Moreover, development of the LES methodology includes special attention to two boundary conditions: the upstream (inflow) and wall boundary conditions. The upstream boundary condition is generated by using the so-called recycling technique, in which the instantaneous flow properties are sampled on aplane downstream of the inlet and mapped back to the inlet at each time step. This technique develops the upstream boundary-layer flow together with the inflow turbulence without using any precursor simulation and thus within a single computational domain. The roughness of the terrain surface is modeled by implementing a new wall function into OpenFOAM® during the thesis work. Both, the recycling method and the newly implemented wall function, are validated for the channel flows at relatively high Reynolds number before applying them to the atmospheric flow applications. After validating the LES model over simple flows, the simulations are carried out for atmospheric boundary-layer flows over two types of hills: first, two-dimensional wind-tunnel hill profiles and second, the Bolund hill located in Roskilde Fjord, Denmark. For the twodimensional wind-tunnel hills, the study focuses on the overall flow behavior as a function of the hill slope. Moreover, the simulations are repeated using another wall function suitable for smooth surfaces, which already existed in OpenFOAM® , in order to study the sensitivity of the flow to the surface roughness in ABL flows. The simulated results obtained using the two wall functions are compared against the wind-tunnel measurements. It is shown that LES using the implemented wall function produces overall satisfactory results on the turbulent flow over the two-dimensional hills. The prediction of the flow separation and reattachment-length for the steeper hill is closer to the measurements than the other numerical studies reported in the past for the same hill geometry. The field measurement campaign performed over the Bolund hill provides the most recent field-experiment dataset for the mean flow and the turbulence properties. A number of research groups have simulated the wind flows over the Bolund hill. Due to the challenging features of the hill such as the almost vertical hill slope, it is considered as an ideal experimental test case for validating micro-scale CFD models for wind energy applications. In this work, the simulated results obtained for two wind directions are compared against the field measurements. It is shown that the present LES can reproduce the complex turbulent wind flow structures over a complicated terrain such as the Bolund hill. Especially, the present LES results show the best prediction of the turbulent kinetic energy with an average error of 24.1%, which is a 43% smaller than any other model results reported in the past for the Bolund case. Finally, the validated LES methodology is demonstrated to simulate the wind flow over the existing Muukko wind farm located in South-Eastern Finland. The simulation is carried out only for one wind direction and the results on the instantaneous and time-averaged wind speeds are briefly reported. The demonstration case is followed by discussions on the practical aspects of LES for the wind resource assessment over a realistic inland wind farm.

Tacrolimus (FK506) reduces ischemia-induced hippocampal damage in rats: a 7- and 30-day study

The neuroprotective effect of the immunosuppressant agent FK506 was evaluated in rats after brain ischemia induced for 15 min in the 4-vessel occlusion model. In the first experimental series, single doses of 1.0, 3.0 or 6.0 mg FK506/kg were given intravenously (iv) immediately after ischemia. In the second series, FK506 (1.0 mg/kg) was given iv at the beginning of reperfusion, followed by doses applied intraperitoneally (ip) 6, 24, 48, and 72 h post-ischemia. The same protocol was used in the third series except that all 5 doses were given iv. Damage to the hippocampal field CA1 was assessed 7 or 30 days post-ischemia on three different stereotaxic planes along the septotemporal axis of the hippocampus. Ischemia caused marked neurodegeneration on all planes (P<0.001). FK506 failed to provide neuroprotection to CA1 both when applied iv as a single dose of 1.0, 3.0 or 6.0 mg/kg (experiment 1), and after five iv injections of 1.0 mg/kg (experiment 3). In contrast, the repeated administration of FK506 combining iv plus ip administration reduced CA1 cell death on all stereotaxic planes both 7 and 30 days post-ischemia (experiment 2; P<=0.01). Compared to vehicle alone, FK506 reduced rectal temperature in a dose-dependent manner (P<=0.05); however, this effect did not alter normothermia (37ºC). FK506 reduced ischemic brain damage, an effect sustained over time and apparently dependent on repeated doses and on delivery route. The present data extend previous findings on the rat 4-vessel occlusion model, further supporting the possible use of FK506 in the treatment of ischemic brain damage.

Decreased gastric tone and delayed gastric emptying precede neutrophil infiltration and mucosal lesion formation in indomethacin-induced gastric damage in rats

Gastric antral dysmotility has been implicated in the pathogenesis of indomethacin-induced gastric damage, but the relationship between gastric motor abnormalities and mucosal lesions has not been extensively studied. We investigated whether changes in gastric tone and gastric retention correlate with mucosal lesions and neutrophil migration in indomethacin-induced gastric damage in rats. Indomethacin, either 5 or 20 mg/kg (INDO-5 and INDO-20), was instilled into the stomach, and then gastric damage, neutrophil migration, gastric tone and gastric retention were assessed 1 or 3 h later. Gastric damage was calculated as the sum of the lengths of all mucosal lesions, and neutrophil migration was measured by assaying myeloperoxidase activity. Gastric tone was determined by a plethysmometric method, and gastric retention of either saline or Sustacal® was evaluated by a scintigraphic method. Gastric damage was detectable 3 h after either INDO-5 or INDO-20, but not after 1 h. Neutrophil migration was significantly higher 3 h after INDO-20 as compared with INDO-5 or control group, but not after 1 h. Values of gastric tone 1 and 3 h after either INDO-5 (1 h = 1.73 ± 0.07 ml; 3 h = 1.87 ± 0.03 ml) or INDO-20 (1 h = 1.70 ± 0.02 ml; 3 h = 1.79 ± 0.03 ml) were significantly lower than in controls (1 h = 1.48 ± 0.05 ml; 3 h = 1.60 ± 0.06 ml). Gastric retention of saline was higher 1 h after INDO-5 (58.9 ± 3.3%) or INDO-20 (56.1 ± 3.1%) compared to control (45.5 ± 1.7%), but not after 3 h. There were no differences concerning gastric retention of Sustacal® between the various groups. Indomethacin induced decreased gastric tone and delayed gastric emptying, which precede mucosal lesion and neutrophil infiltration. These results indicate that there is no relationship between these gastric motor abnormalities and mucosal lesion in indomethacin-induced gastropathy.