bluuebunny/crossref_metadata_2025 huggingface dataset:
EMBEDDED MOVING SADDLE POINT AND ITS RELATION TO TURBULENCE IN FLUIDS AND PLASMAS
Authors: HE KAIFEN
Published: July 2004

Hysteresis is a common phenomenon in a type of nonlinear waves. Corresponding to the negative tangential branch of a hysteretic curve the steady wave solutions are unstable due to saddle instability; such a saddle steady wave (SSW) is a moving saddle point in the system. In a model system based on a nonintegrable equation derived in fluid and plasma physics, a clear connection is found between turbulent solutions and the appearance of hystereses. A physical cause underlying this phenomenon is the embedded saddle point. In this review paper we focus on a senario of strong turbulent motion that is related to the saddle point. It is shown that in the reference frame moving with the SSW the nonlinear wave can be transformed into a set of coupled oscillators for which the SSW provides a potential; when the orbit of the oscillators collides with the saddle point a crisis onsets; subsequently occurs another critical event during which the master oscillator gets free from the trapping of the potential, inducing a transition to spatiotemporal chaos. The turbulent state after the transition is actually a special kind of self-organized motion characteristic by on-off imperfect phase synchronization among these oscillators.
Metalloprotease disintegrin-mediated ectodomain shedding of EGFR ligands promotes intestinal epithelial restitution
Authors: Myhre Gennett M. , Toruner Murat , Abraham Susan , Egan Laurence J.
Published: July 2004

EGF receptor (EGFR) promotes intestinal epithelial restitution, an important early process in the reepithelialization of ulcers. During epithelial restitution, the mechanism of EGFR activation is not known. We evaluated the role of TNF-converting enzyme (TACE), a metalloprotease disintegrin that proteolytically processes plasma membrane-anchored EGFR ligand precursors into their mature active forms, in wound-induced EGFR activation and epithelial restitution. With the use of scrape-wounded rat intestinal epithelial-1 (RIE-1) cell monolayers to model epithelial ulceration and restitution, we observed the rapid wound-dependent release of EGFR ligands into culture medium. RIE-1 cells express TACE, and treatment with phorbol ester, an established TACE stimulus, triggered the extracellular release of an EGFR ligand, transforming growth factor-α. Blockade of TACE using TNF processing inhibitor (TAPI-1), a specific hydroxamate inhibitor of metalloprotease disintegrins, prevented release of EGFR ligands from wounded RIE-1 cell monolayers. The restitution of wounded RIE-1 cell monolayers was also dose-dependently inhibited by TAPI-1, establishing the role of metalloprotease disintegrins in this process. These results have established a mechanism of EGFR activation in wounded intestinal epithelium and show an important functional role for metalloprotease disintegrin-mediated ectodomain shedding during intestinal epithelial restitution. Therefore, activation of the TACE-EGFR system might promote the healing of intestinal tract ulcers in patients.
Central Tempol alters basal sympathetic nerve discharge and attenuates sympathetic excitation to central ANG II
Authors: Lu Ning , Helwig Bryan G. , Fels Richard J. , Parimi Sujatha , Kenney Michael J.
Published: July 2004

In the present study, we established dose-response relationships between central administration of 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol, a superoxide dismutase mimetic) and the level of renal sympathetic nerve discharge (SND) and tested the hypothesis that intracerebroventricular (icv) Tempol pretreatment would attenuate centrally mediated changes in SND produced by icv ANG II administration. Urethane-chloralose-anesthetized, baroreceptor-denervated, normotensive rats were used. We found that icv Tempol administration produced dose-dependent sympathoinhibitory, hypotensive, and bradycardic responses. Mean arterial pressure and SND values were significantly increased after icv ANG II (150 ng/kg) administration, and these responses were abrogated after icv pretreatment with Tempol (75 μmol/kg) or losartan. Brain superoxide levels tended to be higher in ANG II-treated rats compared with rats treated with Tempol and ANG II. Tempol pretreatment did not prevent increases in SND level that were produced by acute heat stress, which indicates specificity in the effect of Tempol in reducing sympathoexcitation. These results demonstrate that icv Tempol administration influences central sympathetic neural circuits in a dose-dependent manner and attenuates SND responses to central ANG II infusion.
Effects of nitric oxide synthase inhibitor on decrease in peripheral arterial stiffness with acute low-intensity aerobic exercise
Authors: Sugawara Jun , Maeda Seiji , Otsuki Takeshi , Tanabe Takumi , Ajisaka Ryuichi , Matsuda Mitsuo
Published: July 2004

We previously reported that even low-intensity, short-duration acute aerobic exercise decreases arterial stiffness. We aimed to test the hypothesis that the exercise-induced decrease in arterial stiffness is caused by the increased production of NO in vascular endothelium with exercise. Nine healthy men (age: ∼22–28 yr) performed a 5-min single-leg cycling exercise (30 W) in the supine position under an intravenous infusion of NG-monomethyl-l-arginine (l-NMMA; 3 mg/kg during the initial 5 min and subsequent continuous infusion of 50 μg·kg−1·min−1 in saline) or vehicle (saline) in random order on separate days. The pulse wave velocity (PWV) from the femoral to posterior tibial artery was measured on both legs before and after the infusion at rest and 2 min after exercise. Under the control condition, exercised leg PWV significantly decreased after exercise ( P < 0.05), whereas nonexercised leg PWV did not show a significant change throughout the experiment. Under l-NMMA administration, exercised leg PWV was increased significantly by the infusion ( P < 0.05) but decreased significantly after the exercise ( P < 0.05). Nonexercised leg PWV increased with l-NMMA administration and maintained a significantly higher level during the administration compared with baseline (before the infusion, all P < 0.05). The NO synthase blockade × time interaction on exercised leg PWV was not significant ( P = 0.706). These results suggest that increased production of NO is not a major factor in the decrease of regional arterial stiffness with low-intensity, short-duration aerobic exercise.
Control of myocardial oxygen consumption in transgenic mice overexpressing vascular eNOS
Authors: Walsh E. K. , Huang H. , Wang Z. , Williams J. , de Crom R. , van Haperen R. , Thompson C. I. , Lefer D. J. , Hintze T. H.
Published: July 2004

Our objective was to investigate the potential role of selective endothelial nitric oxide (NO) synthase (eNOS) overexpression in coronary blood vessels in the control of myocardial oxygen consumption (MVo2). Transgenic (Tg) eNOS-overexpressing mice (eNOS Tg) ( n = 22) and wild-type (WT) mice ( n = 24) were studied. Western blot analysis indicated greater than sixfold increase of eNOS in cardiac tissue. Echocardiography in awake mice indicated no difference in cardiac function between WT and eNOS Tg; however, systolic pressure in eNOS Tg mice decreased significantly (126 ± 2.3 to 109 ± 2.3 mmHg; P < 0.05), whereas heart rate (HR) was not different. Total peripheral resistance (TPR) was also decreased (9.8 ± 0.8 to 7.6 ± 0.4 4 mmHg·ml−1·min; P < 0.05) in eNOS Tg. Furthermore, female eNOS Tg mice showed even lower TPR (7.2 ± 0.4 mmHg·ml−1·min) compared with male eNOS mice (8.6 ± 0.5, mmHg·ml·min−1; P < 0.05). Left ventricular slices were isolated from WT and eNOS Tg mice. With the use of a Clark-type oxygen electrode in an airtight bath, MVo2was determined as the percent decrease during increasing doses (10−10to 10−4mol/l) of bradykinin (BK), carbachol (CCh), forskolin (10−12to 10−6mol/l), or S-nitroso- N-acetyl penicillamine (SNAP; 10−7to 10−4mol/l). Baseline MVo2was not different between WT (181 ± 13 nmol·g−1·min−1) and eNOS Tg (188 ± 14 nmol·g−1·min−1). BK decreased MVo2(10−4mol/l) in WT by 17% ± 1.1 and 33% ± 2.7 in eNOS Tg ( P < 0.05). CCh also decreased MVo2, 10−4mol/l, in WT by 20% ± 1.7 and 31% ± 2.0 in eNOS Tg ( P < 0.05). Forskolin (10−6mol/l) or SNAP (10−4mol/l) also decreased MVo2in WT by 24% ± 2.8 and 36% ± 1.8 versus eNOS 31% ± 1.8 and 37% ± 3.5, respectively. N-nitro-l-arginine methyl ester (10−3mol/l) inhibited the MVo2reduction to BK, CCh, and forskolin by a similar degree ( P < 0.05), but not to SNAP. Thus selective overexpression of eNOS in cardiac blood vessels in mice enhances the control of MVo2by eNOS-derived NO.
Feasibility of cardiac microimpedance measurement using multisite interstitial stimulation
Authors: Pollard Andrew E. , Smith William M. , Barr Roger C.
Published: July 2004

This study was designed to test the hypothesis that analyses of central interstitial potential differences recorded during multisite stimulation with a set of interstitial electrodes provide sufficient data for accurate measurement of cardiac microimpedances. On theoretical grounds, interstitial current injected and removed using electrodes in close proximity does not cross the membrane, whereas equilibration of intracellular and interstitial potentials occurs distant from electrodes widely separated. Multisite interstitial stimulation should therefore give rise to interstitial potential differences recorded centrally that depend on intracellular and interstitial microimpedances, allowing independent measurement. Simulations of multisite stimulation with fine (25 μm) and wide (400 μm) spacing in one-dimensional models that included Luo-Rudy dynamic membrane equations were performed. Constant interstitial and intracellular microimpedances were prescribed for initial analyses. Discrete myoplasmic and gap-junctional components were prescribed intracellularly in later simulations. With constant microimpedances, multisite stimulation using 29 total electrode combinations allowed interstitial and intracellular microimpedance measurements at errors of 0.30% and 0.34%, respectively, with errors of 0.05% and 0.40% achieved using 6 combinations and 10 total electrodes. With discrete myoplasmic and junctional components, comparable accuracy was maintained following adjustments to the junctions to reflect uncoupling. This allowed uncoupling to be quantified as relative increases in total junctional resistance. Our findings suggest development of microfabricated devices to implement the procedure would facilitate routine measurement as a component of cardiac electrophysiological study.
Coupled pacing improves cardiac efficiency during acute atrial fibrillation with or without cardiac dysfunction
Authors: Yamada Hirotsugu , Mowrey Kent A. , Popović Zoran B. , Kowalewski William J. , Martin David O. , Thomas James D. , Wallick Don W.
Published: July 2004

Coupled pacing (CP), a method for controlling ventricular rate during atrial fibrillation (AF), consists of a single electrical stimulation applied to the ventricles after each spontaneous activation. CP results in a mechanical contraction rate approximately one-half the rate during AF. Paired stimulation in which two electrical stimuli are delivered to the ventricles has also been proposed as a therapy for heart failure. Although paired stimulation enhances contractility, it greatly increases energy consumption. The primary hypothesis of the present study is that CP improves cardiac function during acute AF without a similar increase in energy consumption because of the reduced rate of ventricular contractions. In a canine model, CP was applied during four stages: sinus rhythm (SR), acute AF, cardiac dysfunction (CD), and AF in the presence of cardiac dysfunction. The rate of ventricular contraction decreased in all four stages as the result of CP. In addition, we determined the changes in external cardiac work, myocardial oxygen consumption, and myocardial efficiency in the each of four stages. CP partially reversed the effects of AF and CD on external cardiac work, whereas myocardial oxygen consumption increased only moderately. In all stages but SR, CP increased myocardial efficiency because of the marked increases in cardiac work compared with the moderate increases in total energy consumed. Thus this pacing therapy may be a viable therapy for patients with concurrent atrial fibrillation and heart failure.
Brief episode of STZ-induced hyperglycemia produces cardiac abnormalities in rats fed a diet rich in n-6 PUFA
Authors: Ghosh Sanjoy , Qi Dake , An Ding , Pulinilkunnil Thomas , Abrahani Ashraf , Kuo Kuo-Hsing , Wambolt Richard B. , Allard Michael , Innis Sheila M. , Rodrigues Brian
Published: July 2004

Diabetic patients are particularly susceptible to cardiomyopathy independent of vascular disease, and recent evidence implicates cell death as a contributing factor. Given its protective role against apoptosis, we hypothesized that dietary n-6 polyunsaturated fatty acid (PUFA) may well decrease the incidence of this mode of cardiac cell death after diabetes. Male Wistar rats were first fed a diet rich in n-6 PUFA [20% (wt/wt) sunflower oil] for 4 wk followed by streptozotocin (STZ, 55 mg/kg) to induce diabetes. After a brief period of hyperglycemia (4 days), hearts were excised for functional, morphological, and biochemical analysis. In diabetic rats, n-6 PUFA decreased caspase-3 activity, crucial for myocardial apoptosis. However, cardiac necrosis, an alternative mode of cell death, increased. In these hearts, a rise in linoleic acid and depleted cardiac glutathione could explain this “switch” to necrotic cell death. Additionally, mitochondrial abnormalities, impaired substrate utilization, and enhanced triglyceride accumulation could have also contributed to a decline in cardiac function in these animals. Our study provides evidence that, in contrast to other models of diabetic cardiomyopathy that exhibit cardiac dysfunction only after chronic hyperglycemia, n-6 PUFA feeding coupled with only 4 days of diabetes precipitated metabolic and contractile abnormalities in the heart. Thus, although promoted as being beneficial, excess n-6 PUFA, with its predisposition to induce obesity, insulin resistance, and ultimately diabetes, could accelerate myocardial abnormalities in diabetic patients.
Effect of soluble epoxide hydrolase inhibition on epoxyeicosatrienoic acid metabolism in human blood vessels
Authors: Fang Xiang , Weintraub Neal L. , McCaw Ryan B. , Hu Shanming , Harmon Shawn D. , Rice James B. , Hammock Bruce D. , Spector Arthur A.
Published: July 2004

We investigated the effects of soluble epoxide hydrolase (sEH) inhibition on epoxyeicosatrienoic acid (EET) metabolism in intact human blood vessels, including the human saphenous vein (HSV), coronary artery (HCA), and aorta (HA). When HSV segments were perfused with 2 μmol/l 14,15-[3H]EET for 4 h, >60% of radioactivity in the perfusion medium was converted to 14,15-dihydroxyeicosatrienoic acid (DHET). Similar results were obtained with endothelium-denuded vessels. 14,15-DHET was released from both the luminal and adventitial surfaces of the HSV. When HSVs were incubated with 14,15-[3H]EET under static (no flow) conditions, formation of 14,15-DHET was detected within 15 min and was inhibited by the selective sEH inhibitors N, N′-dicyclohexyl urea and N-cyclohexyl- N′-dodecanoic acid urea (CUDA). Similarly, CUDA inhibited the conversion of 11,12-[3H]EET to 11,12-DHET by the HSV. sEH inhibition enhanced the uptake of 14,15-[3H]EET and facilitated the formation of 10,11-epoxy-16:2, a β-oxidation product. The HCA and HA converted 14,15-[3H]EET to DHET, and this also was inhibited by CUDA. These findings in intact human blood vessels indicate that conversion to DHET is the predominant pathway for 11,12- and 14,15-EET metabolism and that sEH inhibition can modulate EET metabolism in vascular tissue.
Graded alterations of RBC aggregation influence in vivo blood flow resistance
Authors: Yalcin Ozlem , Uyuklu Murat , Armstrong Jonathan K. , Meiselman Herbert J. , Baskurt Oguz K.
Published: July 2004

Although the effects of red blood cell (RBC) aggregation on low-shear rate blood viscosity are well known, the effects on in vivo flow resistance are still not fully resolved. The present study was designed to explore the in vivo effects of RBC aggregation on flow resistance using a novel technique to enhance aggregation: cells are covalently coated with a block copolymer (Pluronic F-98) and then suspended in unaltered plasma. RBC aggregation was increased in graded steps by varying the Pluronic concentration during cell coating and was verified by microscopy and erythrocyte sedimentation rate (ESR), which increased by 200% at the highest Pluronic level. RBC suspensions were perfused through an isolated in situ guinea pig hindlimb preparation while the arterial perfusion pressure was held constant at 100 mmHg via a pressure servo-controlled pump. No significant effects of enhanced RBC aggregation were observed when studies were conducted in preparations with intact vascular control mechanisms. However, after inhibition of smooth muscle tone (using 10−4M papaverin), a significant change in flow resistance was observed in a RBC suspension with a 97% increase of ESR. Additional enhancements of RBC aggregation (i.e., 136 and 162% increases of ESR) decreased flow resistance almost to control values. This was followed by another significant increase in flow resistance during perfusion with RBC suspensions with a 200% increase of ESR. This triphasic effect of graded increases of RBC aggregation is most likely explained by an interplay of several hemodynamic mechanisms that are triggered by enhanced RBC aggregation.
Ionic mechanisms mediating the myogenic response in newborn porcine cerebral arteries
Authors: Ahmed Abu , Waters Christopher M. , Leffler Charles W. , Jaggar Jonathan H.
Published: July 2004

Mechanisms that underlie autoregulation in the newborn vasculature are unclear. Here we tested the hypothesis that in newborn porcine cerebral arteries intravascular pressure elevates wall tension, leading to an increase in intracellular calcium concentration ([Ca2+]i) and a constriction that is opposed by pressure-induced K+channel activation. Incremental step (20 mmHg) elevations in intravascular pressure between 10 and 90 mmHg induced an immediate transient elevation in arterial wall [Ca2+]iand a short-lived constriction that was followed by a smaller steady-state [Ca2+]ielevation and sustained constriction. Pressures between 10 and 90 mmHg increased steady-state arterial wall [Ca2+]ibetween ∼142 and 299 nM and myogenic (defined as passive-active) tension between 25 and 437 dyn/cm. The relationship between pressure and myogenic tension was strongly Ca2+dependent until forced dilation. At low pressure, 60 mM K+induced a steady-state elevation in arterial wall [Ca2+]iand a constriction. Nimodipine, a voltage-dependent Ca2+channel blocker, and removal of extracellular Ca2+similarly dilated arteries at low or high pressures. 4-Aminopyridine, a voltage-dependent K+(Kv) channel blocker, induced significantly larger constrictions at high pressure, when compared with those at low pressure. Although selective Ca2+-activated K+(KCa) channel blockers and intracellular Ca2+release inhibitors induced only small constrictions at low and high pressures, a low concentration of caffeine (1 μM), a ryanodine-sensitive Ca2+release (RyR) channel activator, increased KCachannel activity and induced dilation. These data suggest that in newborn cerebral arteries, intravascular pressure elevates wall tension, leading to voltage-dependent Ca2+channel activation, an increase in wall [Ca2+]iand Ca2+-dependent constriction. In addition, pressure strongly activates Kvchannels that opposes constriction but only weakly activates KCachannels.
Effects of aging on cardiac and skeletal muscle AMPK activity: basal activity, allosteric activation, and response to in vivo hypoxemia in mice
Authors: Gonzalez Asensio A. , Kumar Reetu , Mulligan Jacob D. , Davis Ashley J. , Saupe Kurt W.
Published: July 2004

Although a diminished ability of tissues and organisms to tolerate stress is a clinically important hallmark of normal aging, little is known regarding its biochemical basis. Our goal was to determine whether age-associated changes in AMP-activated protein kinase (AMPK), a key regulator of cellular metabolism during the stress response, might contribute to the poor stress tolerance of aged cardiac and skeletal muscle. Basal AMPK activity and the degree of activation of AMPK by AMP and by in vivo hypoxemia (arterial Po2 of 39 mmHg) were measured in cardiac and skeletal muscle (gastrocnemius) from 5- and 24-mo-old C57Bl/6 mice. In the heart, neither basal AMPK activity nor its allosteric activation by AMP was affected by age. However, after 10 min of hypoxemia, the activity of α2-AMPK, but not α1-AMPK, was significantly higher in the hearts from old than from young mice ( P < 0.005), this difference being due to differences in phosphorylation of α2-AMPK. Significant activation of AMPK in the young hearts did not occur until 30 min of hypoxemia ( P < 0.01), stress that was poorly tolerated by the old mice (mortality = 67%). In contrast, AMPK activity in gastrocnemius muscle was unaffected by age or hypoxemia. We conclude that the age-associated decline in hypoxic tolerance in cardiac and skeletal muscle is not caused by changes in basal AMPK activity or a blunted AMPK response to hypoxia. Activation of AMPK by in vivo hypoxia is slower and more modest than might be predicted from in vitro and ex vivo experiments.
Time course of air hunger mirrors the biphasic ventilatory response to hypoxia
Authors: Moosavi S. H. , Banzett R. B. , Butler J. P.
Published: July 2004

Determining response dynamics of hypoxic air hunger may provide information of use in clinical practice and will improve understanding of basic dyspnea mechanisms. It is hypothesized that air hunger arises from projection of reflex brain stem ventilatory drive (“corollary discharge”) to forebrain centers. If perceptual response dynamics are unmodified by events between brain stem and cortical awareness, this hypothesis predicts that air hunger will exactly track ventilatory response. Thus, during sustained hypoxia, initial increase in air hunger would be followed by a progressive decline reflecting biphasic reflex ventilatory drive. To test this prediction, we applied a sharp-onset 20-min step of normocapnic hypoxia and compared dynamic response characteristics of air hunger with that of ventilation in 10 healthy subjects. Air hunger was measured during mechanical ventilation (minute ventilation = 9 ± 1.4 l/min; end-tidal Pco2 = 37 ± 2 Torr; end-tidal Po2 = 45 ± 7 Torr); ventilatory response was measured during separate free-breathing trials in the same subjects. Discomfort caused by “urge to breathe” was rated every 30 s on a visual analog scale. Both ventilatory and air hunger responses were modeled as delayed double exponentials corresponding to a simple linear first-order response but with a separate first-order adaptation. These models provided adequate fits to both ventilatory and air hunger data ( r2 = 0.88 and 0.66). Mean time constant and time-to-peak response for the average perceptual response (0.36 min−1 and 3.3 min, respectively) closely matched corresponding values for the average ventilatory response (0.39 min−1 and 3.1 min). Air hunger response to sustained hypoxia tracked ventilatory drive with a delay of ∼30 s. Our data provide further support for the corollary discharge hypothesis for air hunger.
Regulation of fuel metabolism by preexercise muscle glycogen content and exercise intensity
Authors: Arkinstall Melissa J. , Bruce Clinton R. , Clark Sally A. , Rickards Caroline A. , Burke Louise M. , Hawley John A.
Published: July 2004

To date, the results of studies that have examined the effects of altering preexercise muscle glycogen content and exercise intensity on endogenous carbohydrate oxidation are equivocal. Differences in the training status of subjects between investigations may, in part, explain these inconsistent findings. Accordingly, we determined the relative effects of exercise intensity and carbohydrate availability on patterns of fuel utilization in the same subjects who performed a random order of four 60-min rides, two at 45% and two at 70% of peak O2 uptake (V̇o2 peak), after exercise-diet intervention to manipulate muscle glycogen content. Preexercise muscle glycogen content was 596 ± 43 and 202 ± 21 mmol/kg dry mass ( P < 0.001) for high-glycogen (HG) and low-glycogen (LG) conditions, respectively. Respiratory exchange ratio was higher for HG than LG during exercise at both 45% (0.85 ± 0.01 vs. 0.74 ± 0.01; P < 0.001) and 70% (0.90 ± 0.01 vs. 0.79 ± 0.01; P < 0.001) of V̇o2 peak. The contribution of whole body muscle glycogen oxidation to energy expenditure differed between LG and HG for exercise at both 45% (5 ± 2 vs. 45 ± 5%; P < 0.001) and 70% (25 ± 3 vs. 60 ± 3%; P < 0.001) of V̇o2 peak. Yet, despite marked differences in preexercise muscle glycogen content and its subsequent utilization, rates of plasma glucose disappearance were similar under all conditions. We conclude that, in moderately trained individuals, muscle glycogen availability (low vs. high) does not influence rates of plasma glucose disposal during either low- or moderate-intensity exercise.
Urine of Patients with Nephrotic Syndrome Contains the Plasma Type of PAF-Acetylhydrolase Associated with Lipoproteins
Authors: Balafa Olga C. , Karabina Sonia-Athena P. , Pappas Charalambos A. , Elisaf Moses , Tselepis Alexandros D. , Siamopoulos Kostas C.
Published: July 2004

Background: Platelet-activating factor (PAF) is a proinflammatory phospholipid mediator involved in the pathogenesis of glomerulonephritis (GN). In plasma, PAF is hydrolyzed and inactivated by PAF-acetylhydrolase (PAF-AH), an enzyme associated with lipoproteins, mainly with the low-density lipoprotein. PAF-AH activity has been found in urine of patients with primary GN, however the source and type of urinary PAF-AH remain unknown. We characterized the type of PAF-AH excreted in the urine of patients with primary GN and studied the possible relationship of this enzyme with the lipiduria and proteinuria observed in these patients. Methods: Eighteen patients with primary GN (8 with nephrotic syndrome (NS) and 10 with non-nephrotic range proteinuria (NNRP)) and 20 normolipidemic age- and sex-matched controls participated in the study. PAF-AH activity in plasma, in urine and in individual lipoprotein particles was determined by the trichloroacetic acid precipitation procedure, whereas the PAF-AH protein was detected by Western blotting analysis. Plasma and urine lipoproteins were fractionated by gradient ultracentrifugation and characterized by Western blotting analysis. Results: Plasma PAF-AH activity was higher in NS patients compared with NNRP patients and controls, whereas the enzyme activity associated with high-density lipoprotein was significantly lower in both patient groups compared with controls. PAF-AH was detected only in the urine of NS patients. It was the plasma type of PAF-AH and was associated with lipoprotein particles. Enzyme activity was also positively correlated with urine cholesterol levels. Conclusion: Urine of NS patients contains the plasma type of PAF-AH, which is related to the extent of lipiduria and is associated with urine lipoproteins.
A Community-Based Epidemiologic Study on Gallstone Disease among Type 2 Diabetics in Kinmen, Taiwan
Authors: Liu Chi-Ming , Tung Tao-Hsin , Liu Jorn-Hon , Lee Wen-Ling , Chou Pesus
Published: July 2004

Background: This study was conducted to assess the prevalence and associated risk factors of gallstone disease (GSD) among type 2 diabetics in Kinmen, Taiwan. Methods: Based on a total of 858 type 2 diabetics ascertained in 1991–1993, an ultrasound sonography screening was performed by a panel of specialists in 2001. A total of 440 (51.3%) subjects were examined. Results: Sixty-three out of 440 type 2 diabetics were diagnosed with GSD. The overall prevalence of GSD was 14.4%, including single stone 8.0% (n = 35), multiple stones 3.2% (n = 14), and cholecystectomy 3.2% (n = 14). The significant risk factors of GSD based on multiple logistic regression analysis were age (OR = 1.06, 95% CI: 1.02–1.10) and BMI (OR = 1.11, 95% CI: 1.01–1.22). Conclusions: Our results found that older age and higher BMI may increase the risk of developing GSD in type 2 diabetics.
Language Acquisition in Relation to Cumulative Posttraumatic Stress Disorder Symptom Load over Time in a Sample of Resettled Refugees
Authors: Söndergaard Hans Peter , Theorell Töres
Published: July 2004

Objective: To study the effects of symptoms of posttraumatic stress disorder (PTSD), depression and dissociation as well as cumulative symptom load on language learning during the introduction phase in resettled refugees. Method: Participants were resettled refugees of Iraqi origin. They were assessed by means of a structured interview for PTSD at baseline as well as self-rating questionnaires. Language acquisition was studied by means of register data from the school system. Five levels of language proficiency were recorded. Self-reported symptom scores for PTSD, depression and dissociation (Impact of Events Scale-22, Hopkins Symptom Checklist-25, Dissociative Experiences Scale) were measured at four time points during 9 months immediately after resettlement. In 49 participants in a longitudinal study, data regarding progress in language studies were accessible. Results: The results of the study indicate that the speed of language acquisition – the number of levels taken during the study, adjusted to hours of school presence – is related to the cumulative PTSD symptom load over time (Events Scale-22), but is not related neither to the symptom load of depression and dissociation, nor to the number of previous school years. Conclusion: The study shows that the symptom load of PTSD during the follow-up period is significantly inversely related to the speed of language acquisition in refugees. This implies that treatment as well as preventive measures against worsening of PTSD symptoms are important in order to minimise harmful post-migration stress for the facilitation of integration.
Organ Procurement in Experimental Pancreas Transplantation with Minimal Microcirculatory Impairment
Authors: Drognitz O. , von Dobschuetz E. , Kissler H. , Liu X. , Obermaier R. , Neeff H. , Hopt U.T. , Benz S.
Published: July 2004

Background: Ischemia-reperfusion injury has been shown to deteriorate microcirculation in experimental pancreas transplantation. However, minor concern was taken on the impact of organ procurement in this condition. We examined the impact of a standardized technique of organ procurement on microcirculation and apoptosis in experimental pancreas transplantation. Methods: Male Lewis rats were divided into three groups: sham-operated animals without dissection of the pancreas served as controls (n = 5); animals undergoing nearly total process of organ procurement with the pancreas pedunculated on the aorta and the hepatoduodenal ligament (n = 7), and animals receiving pancreaticoduodenal transplantation. Pancreatic grafts were preserved for 6 h in cold University of Wisconsin solution (n = 7). At 1 and 2 h reperfusion and in time-matched controls, microcirculation was assessed by means of intravital fluorescence microscopy. Tissue samples were obtained after 2 h measurement and DNA breaks of acinar cells were detected by in situ nick end-labeling (TUNEL assay). The apoptotic index (apoptotic cells per high- power fields; hpf) was quantified by microscopic counting of at least 50 hpf. Results: Assessment of functional capillary density (FCD) in animals undergoing subtotal process of organ procurement revealed a slight non-significant decrease at 1 and 2 h compared with controls. In addition, leukocyte sticking to postcapillary venules (LAV) as well as the apoptotic index were found slightly increased after organ procurement compared with controls (p > 0.05). However, after pancreas transplantation the apoptotic index and the LAV were significantly increased and the FCD significantly decreased compared with both groups of non-transplanted animals (p < 0.01). Conclusions: Our validated technique of organ procurement does not negatively impact microcirculation and apoptosis in experimental pancreas transplantation.
Indocyanine Green Fluorescence Measurement of Intestinal Transit and Gut Perfusion after Intestinal Manipulation
Authors: Behrendt F.F. , Tolba R.H. , Overhaus M. , Hirner A. , Minor T. , Kalff J.C.
Published: July 2004

Background and Aims: Postoperative ileus is a common and poorly understood problem of abdominal surgery. The aim of this study was to measure postoperative intestinal transit and to evaluate bowel wall perfusion by a novel in vivo indocyanine green (ICG)-fluorescence measurement following intestinal manipulation (IM). Methods: Rats underwent a simple intestinal manipulation. Myeloperoxidase-positive cells in the muscularis were stained with the Hanker-Yates reaction and quantified histochemically. Bowel wall perfusion was determined directly and 24 h postoperatively using a laser-fluorescence detection unit. Intestinal transit was visualized 24 h after IM. Results: IM resulted in a massive infiltration (155-fold) of neutrophils into the intestinal muscularis 24 h postoperatively. Bowel wall perfusion significantly decreased directly and 24 h following surgery (29 and 59%, respectively). Gastrointestinal transit was similarly impaired and showed a reduction to 40% of the control values 24 h after IM. Conclusion: IM of the rat small intestine caused an impairment in bowel wall perfusion and microcirculation and a significant decrease in gastrointestinal transit. The ICG fluorescence measurement using the described system proved to be a simple and reliable method to evaluate intestinal transit and bowel wall microcirculation in vivo.
Consensus on the Use of Substituted Benzamides in Psychiatric Patients
Authors: Racagni Giorgio , Canonico Pier Luigi , Ravizza Luigi , Pani Luca , Amore Mario
Published: July 2004

The class of substituted benzamides includes compounds able to modulate dopaminergic neurons selectively and specifically. The first synthetic substituted benzamide was sulpiride, which has been replaced in the clinic by the more modern amisulpride. The compound is very selective for mesolimbic D2 and D3 receptors and, therefore, has a dual mechanism of action, which is associated with two different indications. At low doses (50 mg), amisulpride preferentially blocks presynaptic autoreceptors, producing an increase in dopamine release, and therefore acting as a dopaminergic compound able to resolve the dopaminergic hypoactivity that characterizes depression. At higher doses (400–1,200 mg), the drug exerts its activity on postsynaptic D3/D2 receptors located in the limbic region and prefrontal areas, producing selective dopaminergic inhibition, eliciting antipsychotic effects. In the present review, the clinical use of amisulpride in depressive syndromes is discussed, in particular in dysthymia and in schizophrenia. Based on experimental data, amisulpride is a treatment of choice for dopaminergic transmission disorders, both in depression and in schizophrenia.
P300 Event-Related Potential Amplitude and Impulsivity in Cocaine-Dependent Subjects
Authors: Moeller F. Gerard , Barratt Ernest S. , Fischer Christian J. , Dougherty Donald M. , Reilly Edward L. , Mathias Charles W. , Swann Alan C.
Published: July 2004

Previous studies report reduced amplitude of the P300 event-related potential in cocaine-dependent individuals. Cocaine dependence is also associated with increased impulsivity, possibly due to deficits in cognitive function that are associated with reduced P300 amplitude. In the current study, the relationship between cocaine dependence, impulsivity, and P300 amplitude were examined. An auditory oddball event-related potential task along with self-report (Barratt Impulsiveness Scale version 11) and behavioral laboratory (Immediate and Delayed Memory Task) measures of impulsivity were assessed in healthy controls (n = 14) and subjects who met DSM-IV criteria for current cocaine dependence (n = 17). P300 amplitude was reduced and self-reported and behavioral laboratory impulsivity scores were elevated among the cocaine-dependent group compared to controls. There was a positive correlation between the questionnaire and behavioral laboratory measures of impulsivity, and a negative correlation between impulsivity measures and P300 amplitude. The correlation between self-reported impulsivity scores and P300 amplitude remained after taking into account the number of childhood conduct disorder symptoms. This study supports the hypothesis that the basic neurophysiology responsible for the P300 amplitude in cocaine-dependent individuals is associated with impulsivity independent of a history of childhood conduct disorder symptoms.
Impaired Neuroendocrine Response to Stress following a Short-Term Fat-Enriched Diet
Authors: Kitraki Efthimia , Soulis George , Gerozissis Kyriaki
Published: July 2004

Unbalanced diets and stressful situations disrupt energy homeostasis and are implicated in the development of severe pathologies. The present study investigated the effects of a 7-day diet, enriched in corn oil (20%) and proportionally lower in protein and carbohydrate, on the major regulators of energy expenditure and stress response of adult male Wistar rats exposed to acute swimming stress at the end of the dietary treatment. Food intake and body weight gain were lower in diet-fed as compared with normal-chow-fed controls. The circulating leptin levels were elevated in both nonstressed and stressed diet-fed rats, while the glucose levels were significantly increased only in the diet-fed group subjected to stress. The plasma insulin levels were not affected by the diet, but were significantly reduced in acutely stressed rats. Acute swimming increased corticosterone levels both in chow-fed and diet-fed rats. No significant effect of diet was observed on corticosterone levels. Northern blot analysis showed increased glucocorticoid receptor mRNA levels in the hypothalamus of normally fed rats subjected to stress. This increase was not observed in the diet-fed stressed group, which on the contrary showed reduced glucocorticoid receptor mRNA levels following stress. The data presented indicate that even a moderately unbalanced, fat-enriched diet can within a short time disrupt the metabolic neuroendocrine balance and the stress response, rendering the organism more vulnerable to potential stressful insults.
Does a Nephron Deficit in Rats Predispose to Salt-Sensitive Hypertension?
Authors: Zimanyi Monika A. , Bertram John F. , Black M. Jane
Published: July 2004

Aim: This study tested the hypothesis that a nephron deficit predisposes rats to salt-sensitive hypertension in adulthood. Methods: Female Wistar-Kyoto rats were fed a low (9%) or a normal (20%) protein diet during pregnancy and lactation. Male, birth-weight-matched offspring were paired. One rat from each pair was perfusion fixed at 4 weeks of age and the other rat at 40 weeks of age. Kidneys were removed and nephron number and total renal filtration surface area (FSA) determined using unbiased stereological techniques. The rats that were allowed to grow to adulthood had tail-cuff systolic blood pressure and body weight determined twice weekly. Between 30 and 40 weeks of age, a normal or a high-salt diet was fed to the rats. Results: The offspring of rats fed the low-protein diet were significantly smaller at birth, and at 4 weeks of age they had a significant reduction in kidney volume, nephron number, and total renal FSA when compared to controls. Tail-cuff systolic blood pressure in the offspring from 4 to 29 weeks of age did not significantly differ between the two groups. Administration of a high-salt diet from 30 to 40 weeks of age led to a significant increase in blood pressure in both dietary treatment groups; however, it was not exacerbated in the rats exposed to the low-protein diet in utero. Conclusions: Maternal protein restriction in rats did not lead to salt-sensitive hypertension. Nephron endowment and FSA did not correlate with blood pressure in adulthood.
Combination Therapy with Angiotensin-Converting Enzyme Inhibitor and Oral Adsorbent of Uremic Toxins Can Delay the Appearance of Glomerular Sclerosis and Interstitial Fibrosis in Established Renal Failure
Authors: Okada Kazuyoshi , Okawa Erina , Shibahara Hiroshi , Maruyama Takashi , Maruyama Noriaki , Matsumoto Koichi , Takahashi Susumu
Published: July 2004

Background/Aim: Angiotensin II plays a central role in the progression of chronic renal failure (CRF), and administration of angiotensin-converting enzyme inhibitor (ACEI) in rats delays the progression of CRF. However, ACEI has little effect on CRF progression in rats with established CRF. We therefore examined whether combination therapy with ACEI and oral adsorbent for uremic toxins in the gastrointestinal tract has the desired effect. Methods: Rats subjected to subtotal nephrectomy were given enalapril at 20 mg/kg (n = 10, group E), AST-120 at 5 g (n = 10, group A), enalapril and AST-120 together at the same doses (n = 10, group EA), or no treatment (n = 10, group C) 8 weeks after the operation. The substances were administered in 100 g rat chow. All animals were pair-fed, and all were killed after 8 weeks of pair-feeding. Results: Body weight did not differ between groups during the study. Blood pressure at week 8 was significantly lower in groups E and EA than in groups C and A (p < 0.05). Urinary protein excretion level and renal plasma flow rate at week 8 were significantly less in groups E and EA than in group C (p < 0.05, p < 0.01). The glomerular filtration rate at week 8 was significantly higher in group EA than in group C (p < 0.05). The glomerular sclerosis index and interstitial fibrosis area at week 8 were significantly less in group EA than in group C (p < 0.01). Conclusion: ACEI and AST-120 in combination can delay progression of established CRF in rats by inhibiting the appearance of glomerular sclerosis and interstitial fibrosis.
Acute Effects of Nonlethal in utero Hypoxia on Fetal Guinea Pig Heart and Lack of Persistent Cardiac or Cerebral Effects in the Neonate
Authors: Powell Saul R. , Mantell Lin L. , Garramone Valerie , Drexler Steven , Teichberg Saul
Published: July 2004

This study assesses the vulnerability of fetal guinea pig heart to metabolic changes during acute nonlethal in utero hypoxia. Guinea pigs (50–55 days gestation) were exposed to 7% O2 for 2 h and room air for 4 h. Fetal hearts were harvested before hypoxia, at the end of hypoxia, and 4 h after hypoxia, and analyzed for: apoptosis (TUNEL), histology, lipid peroxidation and ATP. A group of posthypoxic dams was taken to gestation. Within 48 h postpartum, the function of neonatal hearts was tested and cerebral histology examined. Fetal heart ATP was decreased by 27% at the end of hypoxia and by 32% 4 h after hypoxia. The lipid peroxides, 4-hydroxynonenal and malondialdehyde, were decreased by 37 and 46%, respectively, by 4 h after hypoxia. The apoptotic index increased from 2% in prehypoxic hearts to 8.4% by 4 h after hypoxia. Fetal heart morphology was unremarkable. Postpartum neonatal cardiac function was not affected and cerebral histology was unremarkable. These results support the conclusion that nonlethal in utero hypoxia has acute effects on the fetal heart but no persistent cardiac or cerebral effects in the postpartum neonate.
Blink Reflex Abnormalities in Chronic Alcoholics
Authors: Nazlıel B. , Arıkan Z. , İrkeç C. , Karakılıç H.
Published: July 2004

Purpose: The aim of the present study was to evaluate the efficacy of blink reflex as a method for obtaining early diagnosis of cranial nerve involvement in alcoholic patients. Materials and Methods: The study was conducted on 30 male alcoholics with a mean age of 43 years. They had histories of alcohol abuse for at least 6 years (mean: 25). At the time of recording, they had undergone detoxification treatment for a mean of 27 days. Results: R1 (early response), R2Y (second ipsilateral response), and R2C (second contralateral response) latencies in alcoholics were prolonged relative to controls and the differences were statistically significant (p < 0.02, p < 0.001, p < 0.001, respectively). According to the defined criteria, 40% of the patients had abnormal responses, and the most common abnormality was the unilateral prolongation of R1 (13%). Conclusion: Finding abnormal blink reflex responses in alcoholic patients has suggested that blink reflex testing is a useful method for the evaluation of subclinical cranial nerve involvement in alcoholic patients. Blink reflex testing may be useful in detecting early changes and in the follow-up of alcoholic disorder.
First-Year Results of the Third Stroke Registry in Tartu, Estonia
Authors: Vibo Riina , Kõrv Janika , Haldre Sulev , Roose Mai
Published: July 2004

Background: The main goal of the Third Stroke Registry in Tartu was to determine the incidence and 28-day case-fatality rates for first-ever stroke in an Estonian population. Methods: The data collection started on 01.12.2001. All patients with first-ever stroke living in Tartu were registered. Results: During the first year, 234 first-ever stroke cases were registered. The incidence rate of first-ever stroke age-standardised to the European population was 195/100,000, 214 (95% CI, 185–243) for men and 181 (95% CI, 155–208) per 100,000 for women. Sixty-eight patients (29%) died within 28 days of stroke onset. Conclusions: The incidence and 28-day case-fatality rate of stroke in Estonia are high compared to other countries. It might be related to higher risk factor prevalence, stress and socioeconomic status.
The Evaluation of Wallerian Degeneration in Chronic Paediatric Middle Cerebral Artery Infarction Using Diffusion Tensor MR Imaging
Authors: Khong Pek-Lan , Zhou Lin-Jiang , Ooi Gaik-Cheng , Chung Brian H.Y. , Cheung Raymond T.F. , Wong Virginia C.N.
Published: July 2004

Background: The long-term neuromotor outcome in paediatric strokes ranges from normal to varying degrees of hemiplegia. We evaluated the indices of diffusion tensor magnetic resonance imaging (DTI), fractional anisotropy and mean diffusivity to determine if these indices can identify and quantify the presence of Wallerian degeneration in paediatric patients with chronic middle cerebral artery infarction, and to determine if these quantitative parameters correlate with the neuromotor outcome. Methods: Eleven children (mean age 8.1 years) with evidence of unilateral middle cerebral artery stroke on magnetic resonance imaging and 10 control subjects (mean age 8.7 years) were studied. Neuromotor outcome was based on functions of the affected hand: mild (n = 3), moderate (n = 6), and severe (n = 2) hemiparesis. Fractional anisotropy and mean diffusivity of the ipsilateral corticospinal tract were compared with matched contralateral regions using the Mann-Whitney U test. Spearman’s test was performed to study the relationship between neuromotor outcome and the following: ipsilateral-to-contralateral ratio of fractional anisotropy, mean diffusivity and cerebral peduncle area, and the largest infarction size. Results: For control subjects, there were no significant differences in fractional anisotropy and mean diffusivity of the corticospinal tract between the right and left side. For patients, fractional anisotropy decreased by 18% and mean diffusivity increased by 8% in the ipsilateral compared to the contralateral corticospinal tract. Neuromotor outcome correlated with the ipsilateral-to-contralateral ratio of fractional anisotropy (r = –0.638, p = 0.035) but not with the mean diffusivity ratio, cerebral peduncle area ratio and largest infarction size. Conclusion: DTI can be used to detect and quantify Wallerian degeneration in chronic paediatric middle cerebral artery infarction. Our preliminary data show that loss of anisotropy in the corticospinal tract correlates with neuromotor outcome.