bluuebunny/crossref_metadata_2025 huggingface dataset:
Active Control of Ionized Boundary Layers
Authors: Mendes R. Vilela
Published: September 2003

The challenging problems, in the field of control of chaos or of transition to chaos, lie in the domain of infinite-dimensional systems. Access to all variables being impossible in this case and the controlling action being limited to a few collective variables, it will not in general be possible to drive the whole system to the desired behavior. A paradigmatic problem of this type is the control of the transition to turbulence in the boundary layer of fluid motion. By analyzing a boundary layer flow for an ionized fluid near an airfoil, one concludes that active control of the transition amounts to the resolution of an generalized integro-differential eigenvalue problem. To cope with the required response times and phase accuracy, electromagnetic control, whenever possible, seems more appropriate than mechanical control by microactuators.
Learning Control of Time-Delay Chaotic Systems and its Applications
Authors: Konishi Keiji , Kokame Hideki
Published: September 2003

The present paper proposes a learning control system that automatically stabilizes one-dimensional time-delayed chaotic systems. We give a systematic procedure to design the control system using a few pieces of uncertain information on the chaotic system. Furthermore, this control system can be applied to a technique that moves a stable orbit of nonchaotic systems to coexistent unstable points and stabilizes the moving orbit onto these unstable points. To check the theoretical results, we demonstrate some numerical experiments.
Chaotic Oscillations in a Chloroplast System Under Constant Illumination
Authors: Smrčinová Miroslava , Sørensen Preben Graae , Krempasky Július , Ballo Peter
Published: September 2003

We show that nonlinear, aperiodic oscillatory behavior can be observed in a chloroplast system by measuring the absorption of light. This behavior depends on illumination of the system with light which is absorbed by chlorophyll. The oscillations can be stopped by addition of acetone indicating that chemical reactions are involved. These observations confirm the role of photosynthesis. The effect of stirring and the statistics of the oscillating part of the spectrum suggest that the buoyancy of oxygen bubbles formed during photosynthesis is an important art of the mechanism.
Influences of Strain-Rate and Stress-State on Dynamic Response of Cement Mortar
Authors: Wang L.-L. , Shi S.-Q. , Chen J.-Y. , Huang D.-J. , Shen L.-J.
Published: September 2003

At high strain rates, the dynamic response of cement mortar, a heterogeneous material with damage, was experimentally studied under three different stress states: (1) one-dimensional stress state by using the SHPB technique, (2) one-dimensional strain state at high pressures from 1 to 5 GPa by using a one-stage gas gun, and (3) quasi one-dimensional strain state by using an improved passive confining SHPB technique. The experimental results indicate that cement mortar is a kind of nonlinear rate-dependent material with internal damage evolution, and that the confining pressure greatly influences its ductility and strength. The main results are given and discussed.
Dynamic Instability of Stiffened Plates with Cutout Subjected to In-Plane Uniform Edge Loadings
Authors: Srivastava A. K. L. , Datta P. K. , Sheikh A. H.
Published: September 2003

This paper is concerned with the dynamic stability of stiffened plates with cutout subjected to harmonic in-plane edge loadings. The plate is modelled using the Mindlin–Reissner plate theory and the method of Hill's infinite determinants is applied to analyze the dynamic instability regions. Stiffened plates with cutout possessing different boundary conditions, aspect ratios, and cutout sizes considering and neglecting in-plane displacements have been analyzed for dynamic instability. The boundaries of the instability regions, including those of the principal one, are computed and presented graphically. These results are given in a non-dimensional form and illustrated by means of numerical examples.
Learning, Public Involvement and Environmental Assessment: A Canadian Case Study
Authors: Diduck Alan , Mitchell Bruce
Published: September 2003

Policy makers and scholars have shown increased interest in the learning outcomes of resource and environmental management initiatives. This applies to environmental assessment (EA) as well as to processes that more explicitly incorporate learning-related objectives, such as adaptive management. Using a transformative framework and a qualitative methodology, in this paper we investigate learning outcomes from involvement in an EA of a major hog processing facility in Brandon, Canada. We also examine implications for EA process design, and the pursuit of key social objectives of sustainability. The extent to which the EA in this case facilitated emancipatory learning was quite limited, that is, the process deviated substantially from the ideal conditions of learning. As well, the EA was at best legitimating, and was by no means participatory, empowering, or equitable. The emancipatory potential of involvement in EA, and opportunities for mutual learning, could be increased with earlier involvement, higher degrees of participation, and more open decision-making.
Blood Withdrawal and Infusion via Umbilical Catheters: Effect on Cerebral Perfusion and Influence of Ibuprofen
Authors: Bray Milena , Stucchi Ilaria , Fumagalli Monica , Pugni Lorenza , Ramenghi Luca , Agosti Massimo , Mosca Fabio
Published: September 2003

Withdrawal and infusion of blood via umbilical catheters can affect cerebral blood flow in preterm infants. We compared the effects on cerebral perfusion of 3 ml/kg blood withdrawal and infusion via umbilical arterial (UAC) and venous (UVC) catheters in 16 infants ≤32 weeks gestation, age <24 h, on mechanical ventilation. Near infrared spectroscopy was used to monitor changes in cerebral oxy- and deoxyhemoglobin, total cerebral hemoglobin (an index of cerebral blood volume; CBV) and HbD (an index of cerebral intravascular oxygenation). In 10 infants the study was repeated 1 h after intravenous administration of 10 mg/kg ibuprofen as prophylaxis against PDA. Withdrawal and infusion via the UVC caused significant MABP and concordant HbD and CBV changes. Smaller modifications were seen following blood withdrawal and infusion via the UAC. Ibuprofen attenuated cerebral hemodynamic changes associated with withdrawal, but not infusion, from UAC and UVC.
Intracranial Pressure during Procedural Pain
Authors: Bellieni Carlo Valerio , Burroni Alessandro , Perrone Serafina , Cordelli Duccio Maria , Nenci Anna , Lunghi Antonietta , Buonocore Giuseppe
Published: September 2003

Physiological changes provoked by pain may threaten the integrity of the CNS. In particular, intracranial pressure (ICP) regulates brain perfusion, and its sudden increase may trigger brain haemorrhage. We measured ICP in 51 healthy newborns (gestational age: 35–41 weeks) during blood sampling, by means of a tonometer applied to the anterior fontanelle. Peak ICP values were compared during 3 different types of blood sampling: from the external jugular vein (JV), by heel prick and by heel prick with sensorial saturation. Sensorial saturation consists in giving sensorial stimuli during pain to arrest the transmission of pain to the cerebral cortex. ICP peak values during heel prick were higher than during JV sampling (mean = 26.22 vs. 21.036 mm Hg; p < 0.0001), though babies who underwent the latter procedure had high ICP values before sampling due to the body position required. Heel prick with sensorial saturation was associated with a lower ICP peak (mean = 11.75 mm Hg) than sampling from JV (p < 0.0001). We concluded that heel prick caused a greater rise in ICP than sampling from JV and that sensorial saturation moderated the rise associated with heel prick.
Impact of Maternal Food Restriction on Cold-Induced Thermogenesis in the Offspring
Authors: Luz J. , Griggio M.A. , Vieira L.V.
Published: September 2003

Food restriction imposed during pregnancy usually leads to many alterations in the development of the conceptus. Some of these alterations can be reverted after birth by adequate nutritional rehabilitation, while there are others which are permanent. The aim of this article is to study the influence of maternal food restriction on offspring thermoregulation. Offspring of dams with food restriction during pregnancy (50%) were fed ad libitum after weaning. Rectal temperature was measured every 15 days from weaning to the 90th day of life. From the 60th to the 90th day the animals were either acclimated at 25 or 5°C. On the 90th day the animals were killed and their carcasses were processed for energy balance analysis and body composition determination. The results showed that animals from food-restricted mothers were not able to maintain body temperature for a longer period of time than the pups from control dams. Energy balance parameters and body composition did not show significant differences between rats from control and food-restriction mothers at the same environmental temperature. Thus, the results suggest that intrauterine food restriction may delay the development of the hypothalamus-thyroid axis which, in turn, may affect brown adipose tissue development leading to inefficient thermoregulation during neonatal life.
Elevated Serum CA 125 Levels in Mitral Stenotic Patients with Heart Failure
Authors: Duman Can , Ercan Ertugrul , Tengiz Istemihan , Bozdemir Huseyin , Ercan H. Ekin , Nalbantgil Istemi
Published: September 2003

Background: Elevated tumor marker levels have been reported in heart failure patients with left ventricular (LV) systolic dysfunction and enlargement. The levels of several tumor markers, including CA 125, CA 19-9, CA 15-3 and CEA, in rheumatic mitral stenotic patients were compared to the control group. Materials and Methods: Tumor markers were measured in 60 mitral stenotic patients and in 30 normal subjects who served as the control group. Mitral stenotic patients were classified into two categories of cardiac dysfunction based on the classification of the New York Heart Association (NYHA). Group I consisted of 31 patients in NYHA class 3–4 and group II of 29 patients in NYHA class 1–2. Echocardiographic examinations and invasive hemodynamic monitoring were performed in all patients. Results: Group I patients had decreased mitral valve area (p = 0.004) and higher left atrial diameter (p = 0.003) than group II patients. Right atrial, mean pulmonary artery and pulmonary capillary wedge pressures and transmitral gradient were higher in group I than in group II (p = 0.010, 0.0001, 0.0001 and 0.0001, respectively). CA 125 levels were statistically higher in mitral stenotic patient groups than in the control group (p < 0.0001). No statistically significant differences were shown for the other tumor markers. Group I patients had higher CA 125 levels compared to group II (p < 0.0001). Conclusion: Elevated CA 125 levels may be due to venous congestion and activation of peritoneal mesothelium or increased signal peptides.
Catecholaminergic Activation in Acute Myocardial Infarction: Time Course and Relation to Left Ventricular Performance
Authors: Petersen Claus Leth , Nielsen Jens Rokkedal , Petersen Bodil Laub , Kjær Andreas
Published: September 2003

Aim: The study was designed to assess (1) the time course of catecholaminergic activation in acute myocardial infarction (AMI) as estimated by adrenaline (ADR) and noradrenaline (NOR) concentrations, and (2) to relate activation of these hormones to predict the outcome of cardiac performance. Patients and Methods: Eighteen patients with first AMI were studied. Blood samples were drawn within the first 4–18 h, after 18–24 h, on day 2, day 3 and on day 6 as well as after 1 year. Radionuclide ventriculography was performed on the day of discharge and after 1 year to determine left-ventricular ejection fraction (LVEF). Results: In the study group as a whole, the concentrations of ADR decreased from (mean ± SEM) 0.80 ± 0.12 nmol/l on admission to 0.33 ± 0.03 nmol/l at discharge (p < 0.05). NOR decreased from 4.19 ± 0.78 to 2.44 ± 0.33 nmol/l (p < 0.05). Initial peak concentrations of both ADR and NOR on admission were correlated to LVEF at discharge (r = –0.56, p < 0.05 and r = –0.72, p < 0.05, respectively). If NOR was normal (<3 nmol/l) at admission, the LVEF was normal or almost normal (= 0.46) at discharge. The mean plasma level of ADR and NOR after 1 year follow-up was 0.34 ± 0.04 and 1.95 ± 0.25 nmol/l, respectively. The values after 1 year were unchanged compared to values at discharge, at day 6 (n.s.). Mean LVEF was 0.50 ± 0.03 (range: 0.23–0.69) at discharge and unchanged 0.46 ± 0.05 (range: 0.18–0.72) at 1 year follow-up (n.s.). During hospitalisation, the group with LVEF <0.50 had an 86% higher initial ADR and an 82% higher initial NOR concentration compared to values in patients with LVEF >0.50 (p < 0.05). Conclusion: (1) Catecholaminergic activation, as measured by plasma ADR and NOR in AMI, is acute and restricted to the first 5 days. Thereafter, the hormone levels are normal and stable. (2) The magnitude of the early catecholaminergic activation correlates with left ventricular systolic performance. (3) Normal NOR values at admittance predicts normal or almost normal LVEF at discharge.
Comparison between Second and Third Generation Troponin T Assay in Patients with Symptoms Suggestive of an Acute Coronary Syndrome but without ST Segment Elevation
Authors: Jernberg Tomas , Venge Per , Lindahl Bertil
Published: September 2003

Cardiac troponin T (cTnT) is a useful tool when assessing patients with chest pain and no persistent ST elevation. We compared the 2nd generation with the new, 3rd generation cTnT assay in 750 patients admitted to our coronary care unit because of chest pain. When focusing on patients with cTnT of 0.01–0.20 µg/l, there was a moderate agreement between the methods. According to recent definitions, 35% more patients were classified as having acute myocardial infarction on admission with the 3rd generation assay. The 3rd generation assay also identified a 10% larger low-risk group and was better able to identify patients with signs of very minor myocardial necrosis (cTnT >0.01–0.02 µg/l) and thereby an increased risk of future events. We conclude that the improved precision of the 3rd generation assay does have some clinical implications in terms of improved accuracy of triage and improved prognostic value.
Iron Deficiency Anemia in the Elderly: Prevalence and Endoscopic Evaluation of the Gastrointestinal Tract in Outpatients
Authors: Çoban Erkan , Timuragaoglu Ayşen , Meriç Mehmet
Published: September 2003

Iron deficiency anemia (IDA), mostly due to chronic occult bleeding from the gastrointestinal tract, is a common problem in the elderly. This study aimed to determine the prevalence of IDA in the elderly and to investigate the gastrointestinal tract in elderly patients with IDA. 1,388 patients over 65 years were prospectively evaluated for IDA in our outpatient clinic. IDA was defined if decreased hemoglobin concentrations (<13 g/dl for men and <12 g/dl for women) were associated with low serum ferritin levels (<15 ng/ml in men and <9 ng/ml in women). We evaluated the gastrointestinal system of all patients with IDA by upper gastrointestinal endoscopy and colonoscopy regardless of fecal occult blood loss. The prevalence of anemia was found to be 25% (n = 347) in our study population, and 30.5% (n = 106) of these patients with anemia had iron deficiency. Upper gastrointestinal endoscopy and colonoscopy were performed in 96 patients with IDA. Fifty-eight upper gastrointestinal system lesions (55 patients, 57.3%) and 27 colonic lesions (26 patients, 27.1%) were detected. We diagnosed gastrointestinal malignancy in 15 (15.6%) elderly patients with IDA (8 colon, 1 esophageal and 6 gastric cancers). IDA is a common problem in elderly patients; consequently, before iron replacement therapy, patients should be thoroughly investigated regarding a possible association with gastrointestinal malignancy.
Idiopathic Thrombocytopenic Purpura and Mononeuropathy multiplex
Authors: Ijichi Toshiharu , Muranishi Manabu , Shimura Kazuo , Inaba Toru , Fujita Naohisa , Oka Nobuyuki , Nakagawa Masanori
Published: September 2003

Peripheral neuropathy is an uncommon complication of idiopathic thrombocytopenic purpura (ITP). We report a 61-year-old man with ITP who developed acute-onset mononeuropathy multiplex. An electrophysiologic study revealed active axonal degenerative alteration, and a sural nerve biopsy showed axonal degeneration. Intraneural hemorrhage was suggested to be the most likely cause.
Cyclosporine A in the Treatment of a Patient with Immune Thrombocytopenia Accompanied by Myelodysplastic Syndrome and Nephrotic Syndrome
Authors: Park Soo-Jeong , Han Chi-Wha , Lee Je-Hoon , Eom Hyeon-Seok , Lee Seung-Hun , Jeong Dae-Chul , Lim Ji-Hyang
Published: September 2003

We describe a complete remission with cyclosporine A in a myelodysplastic syndrome (MDS) patient who had a 9-year history of nephrotic syndrome (NS) due to autoimmune nephritis. A 72-year-old woman with MDS and NS rapidly developed thrombocytopenia with multiple spontaneous bleeding episodes and profound proteinuria. She showed persistent platelet refractoriness to platelet transfusions. A flow cytometry examination strongly detected antiplatelet autoantibodies on the surface of her platelets. The treatment with high-dose corticosteroids and intravenous immunoglobulin did not lead to complete improvement in the platelet count, bleedings and proteinuria. However, a low dose of cyclosporine A resulted in a sustained normal range of blood platelet count and negative proteinuria. This finding suggests that, in selected cases, cyclosporine A can be an attractive alternative for MDS patients who also have immune-mediated diseases.
Clarithromycin Inhibits the Development of Dermatitis in NC/Nga Mice
Authors: Hashimoto Yuki , Kaneda Yoshie , Takahashi Nobutaka , Akashi Satoshi , Arai Iwao , Nakaike Shiro
Published: September 2003

Background: Colonization of Staphylococcus aureus on the skin is one of the exacerbating factors of atopic dermatitis (AD). Reduction of bacterial colonization in these lesions was reported to be effective for the treatment of subjects with AD. Clinical trials have demonstrated the efficacy of FK-506 (an immunosuppressive macrolide) ointment for AD, and many case reports have been published regarding its positive effects for other inflammatory skin diseases. Clarithromycin (CAM) is a macrolide antibiotic with immunological effects. One patient with AD was treated effectively with oral CAM for Helicobacter pylori infection. NC/Nga (NC) mice have recently been recognized to be a model of AD. Methods: We examined the effects of CAM on the development of dermatitis, infiltration of mast cells and MHC class II-positive cells in the skin and the colonization of S. aureus on the skin of NC mice. CAM was compared with cefaclor, an antibiotic with no immunological effects. Results: CAM suppressed the development of dermatitis at 5 and 6 weeks to a statistically significant degree, and these effects gradually weakened, but the severity of the dermis of CAM-treated mice was milder than in control mice. Dexamethasone was effective in the case of development of dermatitis at 5 weeks. These effects gradually weakened, and the difference between dexamethasone-treated mice and control mice disappeared. The severity of the skin lesions in CAM-treated mice was the lowest of the three groups at 9 weeks of observation. Histological analyses revealed that infiltration of inflammatory cells, especially degranulated mast cells and MHC class II-positive cells, was significantly reduced. Thickening of the epidermis and hyperkeratosis in CAM-treated mice were less than in control mice. CAM and cefaclor completely inhibited S. aureus on the skin of NC mice, for all experimental periods. Dexamethasone provided inhibition at 5 weeks, but eventually the difference between dexamethasone-treated mice and control mice disappeared. Conclusions: CAM inhibited the development of dermatitis for the first half of the experimental period in NC mice as a result of antibacterial and immunological effects. Our data show that CAM can be an effective antibiotic for AD with respect to delaying the development of dermatitis.
Effect of Antibiotics on Cell Surface Hydrophobicity of Bacteria Causing Orthopedic Wound Infections
Authors: Kustos Tamás , Kustos Ildikó , Kilár Ferenc , Rappai Gábor , Kocsis Béla
Published: September 2003

Background: Despite antibiotic prophylaxis and treatment, the incidence of wound infections in orthopedic surgery is significant. Postoperative wound infection is a multifactorial process, which can be modified by several bacterial factors. Cell surface hydrophobicity of bacteria is a very important physicochemical feature, which has a great influence on the ability of bacteria to adhere to the surface of host cells or medical implants. Methods: In this study, the hydrophobic properties of thirteen bacterial strains (coagulase-negative staphylococci, Staphylococcus aureus and Pseudomonas aeruginosa) isolated from patients with postoperative deep wound infections following orthopedic procedures were determined by the salt aggregation test. Results were compared to the hydrophobicity of three Hungarian standard bacterial strains. The modifying effect of four antibiotics (cefuroxime, cefotaxime, amoxicillin combined with clavulanic acid and amikacin) – applied most often in our Department for prophylaxis and treatment of patients – were analyzed. Results: The cell surface hydrophobicity of certain strains showed considerable changes after antibiotic treatment. These alterations indicated the decrease in hydrophobicity. Supra-inhibitory concentrations (2× minimum inhibitory concentrations, MIC) of the antibiotics were able to induce more frequent alterations in hydrophobicity than sub-inhibitory (0.5× MIC) levels. Conclusions: Alterations in cell surface hydrophobicity caused by antibiotics can modify the adhesion process and thus the pathogenicity of bacterial strains. These changes should be taken into consideration in the management of proper antibiotic prophylaxis and in the treatment of orthopedic patients.
In vitro Activity of Sertaconazole against Dermatophyte Isolates with Reduced Fluconazole Susceptibility
Authors: Carrillo-Muñoz A.J. , Fernández-Torres B. , Cárdenes D.C. , Guarro J.
Published: September 2003

We have studied the in vitro antifungal activity of sertaconazole against 114 dermatophytes with low susceptibility to fluconazole following the National Committee for Clinical Laboratory Standards for filamentous fungi (M38-P). However, several important factors such as the temperature (28 vs. 35°C) and time of incubation (4–10 days vs. 21–74 h), have been found to affect dermatophytes. Isolates were recently recovered from human samples. Sertaconazole was active against 114 isolates of 12 fungal dermatophyte species, showing an overall geometric mean of 0.41 µg/ml with a minimum inhibitory concentration (MIC) range of 0.01–2 µg/ml against these isolates with reduced fluconazole susceptibility. Differences between both antifungals were significant (p < 0.05). MIC50 and MIC90 of sertaconazole were of 0.5 and 1 µg/ml, respectively, while the MIC of fluconazole was ≧16 µg/ml. None of the isolates was resistant to sertaconazole during the study while for four isolates the MIC of fluconazole was ≧64 µg/ml. No evidence of cross-resistance between both antifungals was found.
Topoisomerase I Inactivation by Reticulol and Its in vivo Cytotoxicity against B16F10 Melanoma
Authors: Lim Dae-Seog , Kwak Yi-Sub , Lee Kyung-Ho , Ko Si-Hwan , Yoon Won-Ho , Lee Won-Young , Kim Chang-Han
Published: September 2003

To investigate the enzyme-inhibitory efficacy and the cytotoxicity of reticulol produced from a strain of Streptoverticillium, we conducted a DNA topoisomerase (Topo) cleavage assay and an in vivo assay using B16F10 melanoma. From the inhibition assay of reticulol for Topo I, which is involved in melanoma metastasis, it was seen that Topo I treated with 45 µM reticulol did not replicate or transcribe DNA by forming supercoiled DNA. In the annexin V/propidium iodide staining assay to investigate the death pattern of B16F10 cells treated with 200 µM reticulol, proliferation of B16F10 cells was inhibited due to necrosis. Furthermore, from the in vivo assay, reticulol combined with Adriamycin (a mixture with retinolol 5 mg/kg and Adriamycin 1 mg/kg) further retarded the tumor growth compared to that in mice treated with Adriamycin alone (1 mg/kg). The survival rate of tumor-bearing mice treated with the mixture was closely associated with its cytotoxicity. Taken together, these results suggested that reticulol inactivates Topo I, which is involved in tumor metastasis, and exhibits excellent cytotoxic efficacy against B16F10 melanoma, when combined with Adriamycin, in a mouse model.
Real-Time PCR Quantification of AT1 and AT2 Angiotensin Receptor mRNA Expression in the Developing Rat Kidney
Authors: García-Villalba Pilar , Denkers Nathaniel D. , Wittwer Carl T. , Hoff Charles , Nelson Raoul D. , Mauch Teri Jo
Published: September 2003

Background/Aims: Angiotensin II (Ang II) is an important growth factor in the fetal kidney. Molecular cloning and pharmacological studies have defined two major classes of Ang II receptors designated AT1 and AT2. Two AT1 isoforms, AT1A and AT1B, exist in rodents. AT1 promotes growth and proliferation and mediates many of the known physiological actions of Ang II. AT2 appears to antagonize AT1. Our goal was to measure their relative contributions to Ang II signaling in the developing kidney. Methods: We used real-time RT-PCR to quantify AT1A, AT1B, AT2 and the housekeeping gene EF1α mRNA in kidneys from embryonic (E) day 14–20 and postnatal (P) day 1–14 rats. Results: AT2 mRNA declined from 1.4 × 104 copies/106 copies EF1α on E14 to 4.2 × 103 copies/106 copies EF1α on P14. In contrast, total AT1 mRNA increased gradually from 2.0 × 103 copies/106 copies EF1α on E14 to 2.0 × 104 copies/106 copies EF1α on P14, with AT1A accounting for about 90% of total AT1 mRNA throughout nephrogenesis. Moreover, the ratio of AT2/(AT1A + AT1B) decreased in a log-linear fashion during maturation, from 6.7 on E14 to 0.2 on P14. Conclusion: The ratio of AT2 to AT1 gene expression modulates Ang II action in the developing kidney.
Effects of ‘Non-Calcaemic’ Vitamin D Analogues on 24-Hydroxylase Expression in MG-63 Osteoblast-Like Cells
Authors: Schroeder Neil J. , Burrin Jacky M. , Noonan Kate , Makin Hugh L.J. , Cunningham John
Published: September 2003

Background: New ‘non-calcaemic’ analogues of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) are entering the clinical arena and some of them have been shown to have differential effects in bone. This may have a bearing on the evolution of bone lesions in uraemic patients receiving vitamin D therapies. A potential mechanism for differential effects of analogues lies in their target cell inactivation. Methods: Using a human osteoblastic cell line, MG-63, three analogues, 22-oxacalcitriol (OCT), 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol) and 1α,25-dihydroxydihydrotachysterol2 (1,25(OH)2DHT2), were compared with 1,25(OH)2D3 for (1) their affinity for the vitamin D receptor (VDR) by competitive displacement of tritiated 1,25(OH)2D3 from calf thymus VDR; (2) effects on 24-hydroxylase mRNA expression using comparative RT-PCR, and (3) rates of metabolism, using high performance liquid chromatography, over a 24-hour time course. Results: Relative VDR-binding affinities (IC50) were 1,25(OH)2D3 (100%), OCT (25%), paricalcitol (14%) and 1,25(OH)2DHT2 (0.3%). A ≧3-fold increase in 24-hydroxylase mRNA expression was observed for all compounds at 2 h peaking at 7- to 8-fold above control levels by 12 h, with no significant difference between the analogues and 1,25(OH)2D3. Differences in their rates of metabolism were observed [calculated t½ values = OCT (1.2 h) > paricalcitol (2.3 h) > 1,25(OH)2D3 (2.6 h) > 1,25(OH)2DHT2 (3.4 h)], with OCT having a significantly shorter half-life. Conclusion: In MG-63 cells these analogues up-regulate 24-hydroxylase mRNA expression with similar potency, in each case accelerating ligand inactivation, despite significant differences in VDR affinity. VDR affinity did not correspond to either 24-hydroxylase mRNA expression or the rates of ligand disappearance, suggesting cellular metabolism is one of several factors that determine the analogue specificity of these agents in bone.
The Low Molecular Weight Heparin Enoxaparin Reduces Infarct Size in a Rat Model of Temporary Focal Ischemia
Authors: Quartermain David , Li Yong Sheng , Jonas Saran
Published: September 2003

Low molecular weight heparins (LMWHs) have significantly reduced infarct size in animal studies but they have not been effective in clinical trials, probably because they were administered after ischemic injury had become irreversible. The present study was designed to explore the temporal characteristics of the LMWH enoxaparin with the objective of determining the duration of the treatment window in a rat model of temporary focal ischemia. Focal cerebral ischemia was induced by the intraluminal suture, middle cerebral artery occlusion (MCAO) method. Enoxaparin (10 mg/kg) was administered subcutaneously twice; the first dose was administered to different groups of animals either 1 h before or 1.5, 3, or 5 h after MCAO, and the second 4, 6, 9, or 25 h after the first dose. At 48 h animals were tested for motor coordination and brains were removed for determination of infarct size. Results showed that infarct size and degree of motor impairment were a function of time of the first and the second treatments. If the first treatment was given 1 h prior to MCAO, significant reductions in infarct size were obtained when the second treatment was given up to 6 h after the first (5 h after MCAO), but not when the second dose was given at longer intervals. If the first treatment was given 1.5 h after stroke onset, reduced infarct size was observed only in the group treated for the second time 4 h after the first injection. If the first treatment was given 3 h after MCAO, infarct size was not reduced in any group. However, if enoxaparin was administered intravenously rather than subcutaneously, significant reductions in infarct size were obtained when the first dose was given as long as 5 h after MCAO. These findings indicate that enoxaparin can reduce infarct size in rats when administered prior to stroke onset and suggest that the drug might be considered for prophylactic treatment in a phase 3 clinical trial.
Independent Association of Fibrinogen with Carotid Intima-Media Thickness in Asymptomatic Subjects
Authors: Martínez-Vila Eduardo , Páramo José A. , Beloqui Oscar , Orbe Josune , Irimia Pablo , Colina Inmaculada , Monreal Ignacio , Benito Alberto , Barba Joaquin , Zubieta José L. , Diez Javier
Published: September 2003

Background: Fibrinogen has been found to be an independent risk factor for cardiovascular disease. Both genetic and environmental factors contribute to its variability in plasma. However, whether the relation between fibrinogen and carotid intima-media thickness (IMT) is independent of those factors has not been established. Therefore, the aim of this study was to investigate the relations of plasma fibrinogens and the –455 G/A Bβ-fibrinogen polymorphism with the carotid IMT in a series of asymptomatic subjects. Methods: Markers of inflammation, C-reactive protein (CRP) and leukocytes, and endothelial perturbation (von Willebrand factor, vWF) were measured in 135 subjects. All individuals underwent a complete clinical examination and lipid measurements (cholesterol and its fractions HDL and LDL and triglycerides). The carotid IMT was measured by B-mode ultrasound in the common carotid artery. Results: Patients in the highest fibrinogen tertile had a significantly higher BMI (p < 0.01), LDL-cholesterol (p < 0.01), leukocyte count, CRP and vWF (p < 0.001). In the univariate model a strong positive relationship was found between plasma fibrinogen and carotid IMT (p < 0.01). Fibrinogen also correlated positively with age, BMI, arterial systolic pressure, cholesterol, cholesterol-LDL, smoking, CRP and vWF (p < 0.01). In the multivariate analysis, the association of fibrinogen with carotid IMT remained significant (p < 0.01) after adjustment for all the parameters analyzed. Conclusion: In a population sample of adults without clinically overt atherosclerotic disease, elevated fibrinogen was related to carotid IMT independent of a wide range of important confounding variables.
Polymorphisms of the NADPH Oxidase p22phox Gene in a Caucasian Population with Intracranial Aneurysms
Authors: Krex Dietmar , Ziegler Andreas , König Inke R. , Schackert Hans K. , Schackert Gabriele
Published: September 2003

Background: Vascular remodeling generated by reactive oxygen species contributes to aneurysm formation. The NADPH oxidase system is a major source of superoxide anion not only in phagocytes, but also in endothelial and vascular smooth muscle cells. Polymorphisms of p22phox, an essential component of the NADPH oxidase system, are found to be associated with atherosclerosis, while a recent study found a significant association between the 214C>T polymorphism and the occurrence of ischemic cerebrovascular disease. We conducted a case-control study to investigate the relationship of five polymorphisms of the p22phox gene and the occurrence of cerebral aneurysms. Methods: The study population consisted of 113 patients with intracranial aneurysms and 53 control subjects. The 214C>T polymorphism was investigated by restriction fragment length polymorphism analysis, while polymorphisms 381T>C, 480G>A, 521C>T, and *24A>G were analyzed by direct sequencing of exon 6 and adjacent intronic sequences. Results: The analysis of a primary study sample comprising 35 cases and 28 controls failed to show a significant association between any of the five polymorphisms and the occurrence of intracranial aneurysms using both allele frequencies and genotypes (all nominal p > 0.05). Although there was a deviation from Hardy-Weinberg equilibrium in cases at the 521C>T locus (nominal p < 0.05), this could not be confirmed in a second study sample of 78 patients. Haplotypes were constructed regarding three frequent polymorphisms (214C>T, 521C>T, and *24A>G); haplotype frequencies in cases and controls were not significantly different. Conclusion: Although polymorphisms of the p22phox gene located in the coding region and the 3′-untranslated region were reported to be associated with atherosclerosis and cerebrovascular disease, our data provide evidence that there is no association between these polymorphisms and the occurrence of cerebral aneurysms in Caucasians.
Site of Carotid Plaque Ulceration in Relation to Direction of Blood Flow: An Angiographic and Pathological Study
Authors: Lovett Joanna K. , Rothwell Peter M.
Published: September 2003

Background: Rupture of atherosclerotic plaque is the main cause of acute coronary syndromes and carotid territory ischaemic stroke. Haemodynamic stress is important in early plaque formation and may affect the stability of mature plaques. There is some evidence that macrophage infiltration and plaque rupture tend to localise to the proximal (upstream) part of the plaque where shear stress is highest. However, previous studies have been too small to assess this reliably. We studied the site of ulceration in a large number of carotid plaques. Methods: We studied angiograms of 3,007 symptomatic carotid stenoses, and the pathological appearance of 119 carotid plaques (77 asymptomatic), to identify the presence and position of plaque ulceration. Results: Angiographic ulceration, which was present in 421 patients (14%), was more likely to be proximal than distal to the point of maximum stenosis (OR = 16.6, 95% CI = 11.6–26.9, p < 0.001). This trend increased with severity of stenosis (p = 0.002). Pathological examination of the 119 carotid plaques also showed that ulceration was more likely to occur proximal to the point of maximum stenosis (OR = 6.1, 95% CI = 2.8–13.6, p < 0.001). Conclusions: Ulceration of carotid plaques, visible on angiography or on pathological examination, is seen most often in the proximal (upstream) part where shear stress is highest.
Serial Measurement of Surface Expressions of CD63, P-Selectin and CD40 Ligand on Platelets in Atherosclerotic Ischemic Stroke
Authors: Cha Jae-Kwan , Jeong Min-Ho , Jang Ji-Yeon , Bae Hae-Rahn , Lim Yeong-Jin , Kim Jung Sun , Kim Sang-Ho , Kim Jae Woo
Published: September 2003

Background: Platelet activation is a key step in the progression of atherosclerosis. The CD40 ligand (CD40L) on platelets may be a critical factor to develop the acute vascular events from atheroma. Methods: To determine the role of CD40L on platelets in atherosclerotic ischemic stroke, we serially measured the expressions of CD63, P-selectin and CD40L on platelets in patients with atherosclerotic ischemic stroke (n = 25) and compared them with those in patients with asymptomatic carotid stenosis (n = 20) and in normal subjects (n = 24). Results: The expressions of CD63 and P-selectin on platelets were significantly higher in patients with atherosclerotic ischemic stroke (n = 25) than in normal subjects (n = 24). The extents of surface expressions of CD63 and P-selectin on platelets showed no significant differences between atherosclerotic ischemic stroke and asymptomatic carotid stenosis. However, the CD40L expression on platelets was significantly higher in atherosclerotic ischemic stroke when compared to that in asymptomatic carotid stenosis. Conclusions: In our data, among the population with large artery atherosclerosis, the patients with symptomatic ischemic events showed a significantly elevated expression of CD40L on platelets compared to those without ischemic events. Therefore, the upregulation of CD40L on platelets may be a specific marker of platelet activation to provoke ischemic stroke from large artery atherosclerosis.
Mechanisms Underlying Phase Lag between Systemic Arterial Blood Pressure and Cerebral Blood Flow Velocity
Authors: Kuo Terry B.J. , Chern Chang-Ming , Yang Cheryl C.H. , Hsu Hung-Yi , Wong Wen-Jang , Sheng Wen-Yung , Hu Han-Hwa
Published: September 2003

To explore the mechanisms underlying the phase lag between oscillations in arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV), ABP and CBFV signals were recorded noninvasively from normal volunteers who lay quietly in a supine position. Mean ABP (MAP) and CBFV (MFV) were calculated beat-to-beat by means of integration. Cerebral vascular resistance (CVR) was calculated by dividing MAP with MFV. Frequency domain analysis of MAP, MFV and CVR signals revealed very-low frequency (VLF, 0.016–0.04 Hz), low-frequency (LF, 0.04–0.15 Hz), and high-frequency (HF, 0.15–0.4 Hz) components. The transfer phase of MAP–CVR coupling in the LF and HF range was frequency-dependent, which is equivalent to a time delay of 2 s. However, the transfer phase differed in the CVR–MFV coupling in that the phase was distributed around 180° across the LF and HF ranges. Cross-correlation analysis revealed a positive relationship between MAP–CVR coupling, with MAP leading by 2 s, and a negative relationship between CVR–MFV coupling, with CVR leading by 0.3 s. We concluded that the phase lag between oscillations in ABP and CBFV was chiefly contributed to by the starting latency of cerebral autoregulation (i.e. cerebral vasomotion, revealed by MAP–CVR coupling). Moreover, the negative correlation of the CVR–MFV coupling could offer a different explanation for the physiologic significance of the phase lead of CBFV–ABP oscillations.
Regional Trends in Cerebrovascular Mortality in Germany after Unification (1990–1999)
Authors: Rossnagel Karin , Müller-Nordhorn Jacqueline , Kulig Michael , Willich Stefan N.
Published: September 2003

Background and Purpose: After the unification in 1990 two different health and political systems merged in Germany. Our aim was to analyze trends in mortality from cerebrovascular diseases in the formerly divided western and eastern parts of Germany since the unification. Methods: Trends in mortality were determined by analyzing age-adjusted vital statistics data obtained from the Federal Statistics Office. ICD-9 was used from 1990 to 1997 and ICD-10 in 1998 and 1999. Results: Cerebrovascular mortality declined in Germany between 1991 and 1999 from 104.4 to 72.3 per 100,000 men and from 82.2 to 55.5 per 100,000 women. Mortality rates from cerebrovascular diseases in East Germany were continuously above West German rates: in 1991 the overall rate ratio in East compared to West Germany was 1.6 and in 1999 it was 1.5 in both men and women. This regional variation is mainly due to a higher rate of cerebrovascular diseases being defined as ‘Other’ (ICD-9 437, now ICD-10 I67) in East compared to West Germany. Conclusion: Nearly 10 years after the unification, cerebrovascular mortality is still markedly higher in East compared to the West Germany. Further investigation is needed to determine the causes for the regional variation in cerebrovascular mortality and to improve preventive strategies.
Delayed Cerebrovascular Autoregulatory Response to Ergometer Exercise in Normotensive Elderly Humans
Authors: Heckmann Josef G. , Brown Clive M. , Cheregi Michaela , Hilz Max J. , Neundörfer Bernhard
Published: September 2003

Background: Relatively little is known about physiological cerebrovascular haemodynamics during physical stress in elderly healthy individuals. The aim of this study was to determine the effect of ergometer stress on cerebrovascular haemodynamics in elderly healthy individuals in comparison with young healthy individuals, using non-invasive methods. Methods: Continuous middle cerebral artery blood flow velocity (CBFV; transcranial Doppler ultrasound), beat-to-beat blood pressure, heart rate and transcutaneous pCO2 were measured in response to 3 min ergometer exercise stress in 18 elderly healthy subjects (mean age ± SD 66.5 ± 5.8 years) and 18 healthy young subjects (mean age ± SD 29.4 ± 4.7 years). Pulsatility index (PI) was used as a parameter for cerebrovascular resistance. The subjects were in a supine position with an elevated trunk and performed exercise by pedalling on an ergometer, generating 75–100 W. Statistical analysis was carried out using MANOVA, a general linear model with repeated measures. Results: In both groups, blood pressure increased significantly (p < 0.001) with time during exercise, with no significant differences between the groups or regarding interaction (time sequence/group factor). Heart rate increased significantly with time during exercise (p < 0.001) and was significantly more prominent (p = 0.002) and prolonged (p < 0.001) in the young group. pCO2 did not differ with time or between the groups and with regard to interaction. Mean CBFV (MFV) increased significantly during time (p < 0.001). Between the groups, there was no significant difference (p = 0.836), but with regard to interaction (time sequence/group factor), there was a significant delay in MFV increase in the group of young subjects (p = 0.002). The PI, a measure of cerebrovascular resistance, increased significantly with time without significant differences between the groups (p = 0.061), but was significantly delayed in the elderly regarding the interaction time sequence/group factor (p < 0.001). Conclusion: The cerebrovascular changes during ergometer exercise may reflect the combined activation of the cerebrovascular autoregulative mechanisms (predominantly neurogenic and myogenic). In healthy normotensive elderly subjects, cerebral autoregulatory capacity is retained but delayed in response to ergometer stress compared with young healthy subjects. We speculate that these findings may contribute to a higher risk of cerebral hypoperfusion in the elderly.
Inhibition of Spinal Reflexes by Acetylsalicylate and Metamizol (Dipyrone) in Rats
Authors: Genç O. , Turgut S. , Turgut G. , Kortunay S.
Published: September 2003

The effects of acetylsalicylate and metamizol on spinal monosynaptic reflexes were tested in spinal rats. Adult rats were anesthetized with ketamine, artificially ventilated, and spinalized at the C1 level. A laminectomy was performed in the lumbosacral region. Following electrical stimulation of the sciatic nerve by single pulses, the reflex potentials were recorded from the ipsilateral L5 ventral root. Acetylsalicylate was administered orally via nasogastric tube and metamizol intramuscularly. Acetylsalicylate (50 and 100 mg/kg) and metamizol (15 mg/kg) significantly decreased the amplitude of the reflex response (p < 0.05). But the 10-mg/kg metamizol dose did not significantly decrease the amplitude of the reflex response. The cyclooxygenase products of arachidonic acid may play an important role in regulating the reflex potential.
A Forskolin Derivative, Colforsin Daropate Hydrochloride, Inhibits Rat Mesangial Cell Mitogenesis via the Cyclic AMP Pathway
Authors: Ogata Junichi , Minami Kouichiro , Segawa Kayoko , Yamamoto Chieko , Kim Sung-Teh , Shigematsu Akio
Published: September 2003

A forskolin derivative, colforsin daropate hydrochloride (CDH), has been introduced as an inotropic agent that acts directly on adenylate cyclase to increase intracellular cyclic AMP (cAMP) levels and ventricular contractility, resulting in positive inotropic activity. We investigated the effects of CDH on rat mesangial cell (MC) proliferation. CDH (10–7–10–5 mol/l) inhibited [3H]thymidine incorporation into cultured rat MCs in a concentration-dependent manner. CDH (10–7–10–5 mol/l) also decreased cell numbers in a similar manner, and stimulated cAMP accumulation in MCs in a concentration-dependent manner. A protein kinase A inhibitor, H-89, abolished the inhibitory effects of CDH on MC mitogenesis. These findings suggest that CDH would inhibit the proliferation of rat MCs via the cAMP pathway.
Pharmacokinetics of Isoflurane: Uptake in the Body
Authors: Lu Chih-Cherng , Ho Shung-Tai , Wong Chih-Shung , Wang Jhi-Joung , Tsai Chien-Song , Hu Oliver Yao-Pu , Chang Sun-Yran , Lin Chung-Yuan
Published: September 2003

We investigated the effect of the inspired isoflurane concentration (CIiso) on body uptake by comparing the isoflurane concentration in the pulmonary artery blood (PAiso) and that in the arterial blood (Aiso) in 16 patients undergoing coronary artery bypass grafting surgery during the 1st, hour of isoflurane anesthesia. The patients received standardized anesthetics consisting of fentanyl and thiopental and were then allocated to receive either 1% or 2% CIiso (n = 8 in each group). CIiso and end-tidal isoflurane concentration (CEiso) were measured by infrared analysis, and Aiso and PAiso were analyzed by gas chromatography. The cardiac output was measured by thermodilution by use of a pulmonary artery catheter. The body tissue could be represented by the gradient CIiso–CEiso or Aiso–PAiso over time, respectively. The 2% inspired isoflurane group had twice the gradients (either CIiso–CEiso or Aiso-PAiso) than the 1% inspired isoflurance group. Additionally, both CIiso–CEiso and Aiso–PAiso were nearly constant over the hour of the study. The inspired concentration-dependent and near- constant uptake of isoflurane over time has important implications which enable us to apply the uptake pattern of isoflurane to clinical practice.