bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural regulation of slow-wave frequency in the murine gastric antrum
Authors: Forrest Abigail S. , Ördög Tamás , Sanders Kenton M.
Published: September 2005

Gastric peristaltic contractions are driven by electrical slow waves modulated by neural and humoral inputs. Excitatory neural input comes primarily from cholinergic motor neurons, but ACh causes depolarization and chronotropic effects that might disrupt the normal proximal-to-distal spread of gastric slow waves. We used intracellular electrical recording techniques to study cholinergic responses in stomach tissues from wild-type and W/W V mice. Electrical field stimulation (5 Hz) enhanced slow-wave frequency. These effects were abolished by atropine and the muscarinic M3-receptor antagonist 4-diphenylacetoxy- N-methylpiperidine methiodide. ACh released from nerves did not depolarize antral muscles. At higher rates of stimulation (10 Hz), chronotropic effects were mediated by ACh and a noncholinergic transmitter and blocked by muscarinic antagonists and neurokinin (NK1 and NK2)-receptor antagonists. Neostigmine enhanced slow-wave frequency, suggesting that the frequency of antral pacemakers is kept low by efficient metabolism of ACh. Neostigmine had no effect on slow-wave frequency in muscles of W/W v mice, which lack intramuscular interstitial cells of Cajal (ICC-IM). These muscles also showed no significant chronotropic response to 5-Hz electrical field stimulation or the cholinergic agonist carbachol. The data suggest that the chronotropic effects of cholinergic nerve stimulation occur via ICC-IM in the murine stomach. The capacity of gastric muscles to metabolize ACh released from enteric motor neurons contributes to the maintenance of the proximal-to-distal slow-wave frequency gradient in the murine stomach. ICC-IM play a critical role in neural regulation of gastric motility, and ICC-IM become the dominant pacemaker cells during sustained cholinergic drive.
Plasma protein and blood volume restitution after hemorrhage in conscious pregnant and ovarian steroid-replaced rats
Authors: Blair Martha L. , Mickelsen Deanne
Published: September 2005

We have previously shown that both plasma protein restitution and plasma volume restitution are significantly enhanced in female rats hemorrhaged during the proestrus phase of the estrous cycle. Estradiol and progesterone levels are markedly elevated during proestrus and also increase during pregnancy. The present studies were therefore designed to determine whether the ability to restore plasma protein and blood volume after hemorrhage is augmented during pregnancy and by chronically elevated estradiol levels. The response to moderate hemorrhage (22–23% blood loss) was evaluated in conscious pregnant rats during early and midgestation and compared with that of virgin female rats studied during metestrus. At 22 h posthemorrhage, plasma volume had increased to greater than basal levels, and blood volume was restored to 93 ± 1% (metestrus), 91 ± 2% (early pregnancy), and 98 ± 2% (midgestation) of control ( P > 0.05). Animals hemorrhaged during metestrus or early pregnancy restored the same amount of protein to the plasma as had been removed, whereas those hemorrhaged during midgestation restored nearly 50% more plasma protein than had been removed ( P < 0.01). In ovariectomized animals with chronic steroid replacement that maintained plasma progesterone at metestrus levels (15 ± 2 ng/ml) but raised plasma estradiol to twofold that of midgestation (22 ± 3 pg/ml), the blood volume and plasma protein restitution responses to hemorrhage did not differ from those of ovariectomized animals with no steroid replacement. In summary, posthemorrhage restoration of plasma protein content is significantly augmented during midgestation, but not during early pregnancy. This augmented response cannot be attributed to chronic elevation of plasma estradiol levels alone.
Adipogenic potential of multiple human adenoviruses in vivo and in vitro in animals
Authors: Whigham Leah D. , Israel Barbara A. , Atkinson Richard L.
Published: September 2005

Human adenovirus-36 (Ad-36) increases adiposity in chickens, mice, and nonhuman primates and is associated with human obesity. Ad-36 paradoxically reduces serum cholesterol and triglycerides in animal models. Ad-36 increases adipocyte differentiation and triglyceride accumulation in 3T3-L1 cells in vitro. This study evaluated whether three other human adenoviruses increase adiposity in chickens and in 3T3-L1 cells in vitro. We inoculated chickens with human Ad-2, Ad-31, Ad-37, or media at age 3 wk. Food intake and weights were recorded for 3.5 wk, and then chickens were killed and visceral fat, body composition, serum lipids, and viral antibody status were determined. Visceral fat and total body fat were significantly elevated ( P < 0.001) in the Ad-37 group compared with all other groups. Final body weights were higher in chickens inoculated with Ad-37 compared with Ad-2, but not significantly higher than in control or Ad-31 groups. Food intake did not differ among groups. Serum cholesterol was elevated in Ad-37 chickens compared with control ( P < 0.01) but was not affected by other viruses. Triglycerides were reduced in Ad-37 chickens ( P < 0.0001) but were not affected by other viruses. In 3T3-L1 cells in vitro, Ad-31, Ad-36, and Ad-37, but not Ad-2, increased adipocyte differentiation and triglycerides accumulation. In summary, Ad-37 is another human adenovirus that increases adiposity and reduces serum triglycerides in an animal model. However, the response of serum cholesterol is opposite that of Ad-36. Evaluation of other human adenoviruses to determine their effects on adiposity and serum lipids is warranted, but in vitro assays may not be definitive for this purpose.
Quantitative characterization of airspace enlargement in emphysema
Authors: Parameswaran Harikrishnan , Majumdar Arnab , Ito Satoru , Alencar Adriano M. , Suki Béla
Published: September 2005

The mean linear intercept ( Lm) can be used to estimate the surface area for gas exchange in the lung. However, in recent years, it is most commonly used as an index for characterizing the enlargement of airspaces in emphysema and the associated severity of structural destruction in the lung. Specifically, an increase in Lm is thought to result from an increase in airspace sizes. In this paper, we examined how accurately Lm measures the linear dimensions of airspaces from histological sections and a variety of computer-generated test images. To this end, we developed an automated method for measuring linear intercepts from digitized images of tissue sections and calculate Lm as their mean. We examined how the shape of airspaces and the variability of their sizes influence Lm as well as the distribution of linear intercepts. We found that, for a relatively homogeneous enlargement of airspaces, Lm was a reliable index for detecting emphysema. However, in the presence of spatial heterogeneities with a large variability of airspace sizes, Lm did not significantly increase and sometimes even decreased compared with its value in normal tissue. We also developed an automated method for measuring the area and computed an equivalent diameter of each individual airspace that is independent of shape. Finally, we introduced new indexes based on the moments of diameter that we found to be more reliable than Lm to characterize airspace enlargement in the presence of heterogeneities.
Calcium-independent phospholipase A2modulates cytosolic oxidant activity and contractile function in murine skeletal muscle cells
Authors: Gong Ming C. , Arbogast Sandrine , Guo Zhenheng , Mathenia Jeremy , Su Wen , Reid Michael B.
Published: September 2005

Phospholipase A2(PLA2) activity supports production of reactive oxygen species (ROS) by mammalian cells. In skeletal muscle, endogenous ROS modulate the force of muscle contraction. We tested the hypothesis that skeletal muscle cells constitutively express the calcium-independent PLA2(iPLA2) isoform and that iPLA2modulates both cytosolic oxidant activity and contractile function. Experiments utilized differentiated C2C12myotubes and a panel of striated muscles isolated from adult mice. Muscle preparations were processed for measurement of mRNA by real-time PCR, protein by immunoblot, cytosolic oxidant activity by the dichlorofluorescein oxidation assay, and contractile function by in vitro testing. We found that iPLA2was constitutively expressed by all muscles tested (myotubes, diaphragm, soleus, extensor digitorum longus, gastrocnemius, heart) and that mRNA and protein levels were generally similar among muscles. Selective iPLA2blockade by use of bromoenol lactone (10 μM) decreased cytosolic oxidant activity in myotubes and intact soleus muscle fibers. iPLA2blockade also inhibited contractile function of unfatigued soleus muscles, shifting the force-frequency relationship rightward and depressing force production during acute fatigue. Each of these changes could be reproduced by selective depletion of superoxide anions using superoxide dismutase (1 kU/ml). These findings suggest that constitutively expressed iPLA2modulates oxidant activity in skeletal muscle fibers by supporting ROS production, thereby influencing contractile properties and fatigue characteristics.
Role of 20-HETE in the pial arteriolar constrictor response to decreased hematocrit after exchange transfusion of cell-free polymeric hemoglobin
Authors: Qin Xinyue , Kwansa Herman , Bucci Enrico , Roman Richard J. , Koehler Raymond C.
Published: September 2005

The cerebrovascular response to decreases in hematocrit and viscosity depends on accompanying changes in arterial O2 content. This study examines whether 1) the arteriolar dilation seen after exchange transfusion with a 5% albumin solution can be reduced by the KATP channel antagonist glibenclamide (known to inhibit hypoxic dilation), and 2) the arteriolar constriction seen after exchange transfusion with a cell-free hemoglobin polymer to improve O2-carrying capacity can be blocked by inhibitors of the synthesis or vasoconstrictor actions of 20-HETE. In anesthetized rats, decreasing hematocrit by one-third with albumin exchange transfusion dilated pial arterioles (14 ± 2%; SD), whereas superfusion of the surface of the brain with 10 μM glibenclamide blocked this response (−10 ± 7%). Exchange transfusion with polymeric hemoglobin decreased the diameter of pial arterioles by 20 ± 3% without altering arterial pressure. This constrictor response was attenuated by superfusing the surface of the brain with a 20-HETE antagonist, WIT-002 (10 μM; −5 ± 1%), and was blocked by two chemically dissimilar selective inhibitors of the synthesis of 20-HETE, DDMS (50 μM; 0 ± 4%) and HET-0016 (1 μM; +6 ± 4%). The constrictor response to hemoglobin transfusion was not blocked by an inhibitor of nitric oxide (NO) synthase, and the inhibition of the constrictor response by DDMS was not altered by coadministration of the NO synthase inhibitor. We conclude 1) that activation of KATP channels contributes to pial arteriolar dilation during anemia, whereas 2) constriction to polymeric hemoglobin transfusion at reduced hematocrit represents a regulatory response that limits increased O2 transport and that is mediated by increased formation of 20-HETE, rather than by NO scavenging.
Hypothalamic Proline-Rich Polypeptide Is a Regulator of Oxidative Burst in Human Neutrophils and Monocytes
Authors: Davtyan Tigran K. , Manukyan Hayk A. , Mkrtchyan Nana R. , Avetisyan Samvel A. , Galoyan Armen A.
Published: September 2005

Objective: The effects of proline-rich polypeptide (PRP) isolated from neurosecretory granules of bovine neurohypophysis produced by nuclei supraopticus and paraventricularis on phagocytosis, bacterial intracellular killing and oxidative burst induction in normal human cells and inflammatory cells from patients with Behçet’s disease (BD), i.e. peripheral blood neutrophils and monocytes, were investigated. Methods: Intracellular killing of Staphylococcus aureus by neutrophils and monocytes of normal controls and BD patients, phagocytic activity as well as spontaneous and N-formyl-Met-Leu-Phe (fMLP)- or phorbol 12-myristate 13-acetate (PMA)-induced activation of their respiratory burst were determined by quantitative flow cytometry using highly specific fluorescence probes. Results: PRP does not affect human peripheral blood neutrophil and monocyte phagocytosis but dramatically enhances spontaneous or fMLP- and PMA-induced oxidative burst as well as the intracellular killing of S. aureus. PRP induced the upregulation of the spontaneous or fMLP- and PMA-induced oxidative burst in normal PMNs and monocytes; the number of inflammatory BD cells did neither increase further nor undergo spontaneous or PMA-stimulated oxidative burst. In BD patients, increased spontaneous production of reactive oxygen intermediates (ROIs) by neutrophils and monocytes is characterized by impaired intracellular protein-kinase-C (PKC)-dependent oxidative burst regulation as well as overregulation of chemotaxis/inflammation-mediated respiratory burst induction. PRP restores rather the impaired intracellular PKC-dependent regulation of ROI production in inflammatory diseased cells than the chemotaxis/induction of the inflammation-mediated respiratory burst. Conclusion: We demonstrated the regulatory role for PRP on oxidative burst in neutrophils and monocytes from normal controls and BD patients. Our results suggest that PRP differentially affects both chemotaxis- and PKC-dependent oxidative burst in normal and inflammatory cells from patients.
Expression of Neutral Glycosphingolipids in the Brain, Lymphoid Organs and Lungs of Mice Lacking β2-Microglobulin
Authors: Markotić Anita , Marušić Ana , Müthing Johannes
Published: September 2005

Objectives and Methods:Previous studies have demonstrated the involvement of glycosphingolipid (GSL) antigens in the pathogenesis of immune-mediated neurological disorders such as peripheral neuropathies and multiple sclerosis, as well as in infections of the central nervous system. We investigated the expression of neutral GSLs in the brain, thymus, spleen, and lungs of mice lacking the gene for the β2-microglobulin (β2M), an important component of the MHC class I molecule. Determination of GSL fractions in the tissues of mice homozygous (β2M–/–) or heterozygous (β2M+/–) for β2M gene knockout was performed by high performance thin layer chromatography, followed by immunostaining with specific antibodies. Results: Immunochemical analyses revealed abundant expression of globotetraosylceramide (Gb4), in the brain of β2M–/– mice, compared with undetectable expression in the control β2M+/– mice. The brain of both groups of animals was negative for Gg3, Gg4 and Gb3 immunostaining. Abundant expression of Gg3, Gg4, and Gb3 was found in the lungs of control β2M+/– mice, whereas β2M–/– mice lacked these structures. Immunostaining of Gb4 in the lungs was similar in both groups of animals. The thymus and spleen neutral GSL profiles did not significantly differ between β2M–/– and control animals. Conclusion: This study provides in vivoevidence that globo- and ganglio-series neutral GSL expression in the brain and lungs may be related to the presence of β2M or functional MHC class I molecule, and implicates different modulation of biosynthesis of globo- and ganglio-series neutral GSLs in these tissues.
Risk Factors for Hospital Readmission in Patients with Chronic Obstructive Pulmonary Disease
Authors: Almagro Pedro , Barreiro Bienvenido , Ochoa de Echagüen Anna , Quintana Salvador , Rodríguez Carballeira Mónica , Heredia José L. , Garau Javier
Published: September 2005

Background: Hospital readmissions for acute exacerbation of chronic obstructive pulmonary disease (COPD) are one of the leading causes of healthcare expenditures worldwide. Objectives: To identify risk factors for hospital readmission in COPD patients. Methods:We prospectively evaluated 129 consecutive patients hospitalized for acute exacerbation of COPD. Clinical, spirometric and arterial blood gas variables were measured during hospitalization. Socioeconomic characteristics, comorbidity, dyspnea, functional dependence, depression, social support and quality of life were also analyzed. Readmission was defined as one or more hospitalizations in the following year. Results:During the follow-up period, 75 (58.5%) patients were readmitted. In bivariate analysis, readmission was associated with previous hospitalization for COPD in the past year, dyspnea scale, PaCO2 at discharge, depression, cor pulmonale, chronic domiciliary oxygen and quality of life measured by the St. George’s Respiratory Questionnaire. In multivariate analysis, the best predictor of readmission was the combination of hospitalization for COPD in the previous year (odds ratio, OR: 4.27; 95% confidence interval, CI: 1.5–12), the total score of the St. George’s Respiratory Questionnaire ≧50 points (OR: 2.36; 95% CI: 1.03–5.04) and PaCO2 at discharge ≧45 mm Hg (OR: 2.18; 95% CI: 0.84–5.06). With this model, the probability of readmission for patients without any of these variables was 7%, while it was 70% for the patients with all three variables present. Conclusion: The combination of quality of life, hospitalization for COPD in the previous year and hypercapnia at discharge are useful predictors of readmission at 1 year.
Use of 3-Dimensional Computed Tomography Reconstruction Studies in the Preoperative Assessment of Patients Undergoing Balloon Dilatation for Tracheobronchial Stenosis
Authors: Rooney Cyril P. , Ferguson J. Scott , Barnhart William , Cook-Granroth Janice , Ross Alan , Hoffman Eric A. , McLennan Geoffrey
Published: September 2005

Background: Balloon dilatation (BD) is a useful method of treating tracheobronchial stenosis (TBS); however, accurate preoperative identification of the lesion is difficult. Three-dimensional computed tomography (3D-CT) is an imaging method that may allow more accurate definition of the lesion(s) preoperatively. Study Objective: It is the aim of this study to present our finding using 3D-CT as a part of the preoperative evaluation of patients with TBS undergoing BD. Methods: We studied a prospective case series of 17 consecutive patients who underwent 29 BDs for TBS from a variety of benign and malignant causes at a tertiary care hospital. All patients had a preoperative spiral CT; these data were processed by a software program, VIDA, which was developed at this institution, and 3D-CT reconstruction images of the TBS were created. This enabled accurate preoperative anatomic definition of the lesion. The patients subsequently underwent BD. Results: All 17 patients had lesions identified with 3D-CT. Six patients had tracheal lesions and 12 patients had main stem lesions. One patient had combined tracheal and main stem lesions and 2 other patients had bilateral main stem lesions. Nine out of 17 patients required only one BD. One patient had a failed BD. The remaining 6 patients required more than one BD for optimal results (up to a maximum of 4). The follow-up period ranged from 1 to 34 months. Conclusions: 3D-CT offers accurate definition of TBS, including anatomic location, number of lesions present and status of airway distal to lesion. In this study, all preoperative lesions were correctly identified prior to BD.
Inspiratory Muscle Training May Increase Peak Inspiratory Flow in Chronic Obstructive Pulmonary Disease
Authors: Weiner Paltiel , Weiner Margalit
Published: September 2005

Background: When choosing a specific inhalation device for a chronic obstructive pulmonary disease (COPD) patient, the internal airflow resistance and the ability of the patient to overcome it and to create an optimal inspiratory flow are essential. Objectives: The purpose of the present study was to investigate: (1) the peak inspiratory flow (PIF) that a patient with COPD can generate while breathing through two dry powder inhalers and (2) whether in patients with low PIF specific inspiratory muscle training (SIMT) will increase the PIF and exceed the minimal PIF that is considered necessary to guarantee optimal lung deposition of the drug. Methods: Inspiratory muscle strength and PIFs were measured in 60 patients with COPD. Then 28 patients with severe COPD and low PIF were randomized to receive SIMT or to a control group. Results: With the Turbuhaler, 12 patients (20%) could not generate the optimal flow of 60 l/min. PIF correlated very well with maximal inspiratory mouth pressure (PImax) for the Diskus and the Turbuhaler, as well as for both males and females (p < 0.001). Following the training period, there was a statistically significant increase in the PImax in the training group. This increase was associated with a significant increase in the PIF. All patients overcame the minimal threshold PIF following the training. Conclusions: Some patients with severe COPD are not able to generate adequate flow to secure optimal lung deposition of the inhalation with the Turbuhaler. SIMT improves inspiratory muscle strength as well as PIF. Following 8 weeks of training, the optimal PIF enabling adequate lung deposition of the drug was attained in all the trained patients.
Left Ventricular Dysfunction in Subjects with Mild Secondary Hyperparathyroidism Detected with Pulsed Wave Tissue Doppler Echocardiography
Authors: Iqbal Amjid , Jorde Rolf , Lunde Per , Sundsfjord Johan , Rasmussen Knut
Published: September 2005

Aims: To assess left ventricular function by conventional and pulsed wave tissue Doppler (PWTD) echocardiography in subjects with mild secondary hyperparathyroidism, and to evaluate whether PWTD would be more sensitive than conventional echocardiography in detecting subtle changes in LV systolic and diastolic function. Methods: In the fifth Tromsø study (2001) serum PTH and calcium were measured in 7,954 subjects. One hundred subjects with secondary hyperparathyroidism (SHPT; serum PTH >6.40 pmol/l and serum calcium <2.40 mmol/l) and 106 control subjects with normal PTH and calcium levels and with no history of cardiovascular disease were examined at the follow-up 6–12 months later. Results: Conventional transthoracic echocardiography and PWTD of mitral annulus were successfully performed in 83 cases and 88 controls. At follow-up mean serum PTH values were 6.0 ± 2.2 versus 3.2 ± 1.3 pmol/l (p < 0.05) and mean calcium 2.28 ± 0.10 versus 2.33 ± 0.08 mmol/l (p < 0.05) in cases and controls, respectively. Unpaired t test and multiple linear regression analyses were used. No significant differences in conventional echocardiographic parameters were found. However, PWTD showed reduced systolic velocity in septal, lateral and anterior mitral annulus (p < 0.05) and also reduced early diastolic velocity in septal and anterior mitral annulus (p < 0.05). Conclusion: Subjects with mild SHPT have impaired left ventricular long axis function as evaluated by PWTD compared to conventional echocardiography. PWTD seems to be a more sensitive tool in detecting minor changes in left ventricular function and the new modality should routinely be included in studies evaluating left ventricular function, especially the long axis function.
Effects of Pharmacological Modulation of the ATP-Sensitive Potassium Channels on the Development of Warm-Up Angina Pectoris
Authors: Lindhardt Tommi Bo , Abedini Sadollah , Olesen Rikke Mørch , Haunsø Stig , Gadsbøll Niels
Published: September 2005

The aim of this study was to examine the effect of pharmacological modulation of the ATP-sensitive potassium channels in the development of warm-up angina pectoris. Thirty-one patients with stable angina pectoris, a positive exercise test and angiographically documented coronary artery disease underwent three exercise tests 90 min after receiving either glibenclamide 10.5 mg (an ATP-sensitive potassium channel blocker), pinacidil 25 mg (an ATP-sensitive potassium channel opener) or placebo in a blinded fashion. There was a 30-min recovery period between the first and the second test and 60 min between the second and the third test. The rate-pressure product at 1-mm ST-segment depression (ischemic threshold) and the maximum ST-segment depression (STD) adjusted to the highest rate-pressure product common to the three tests were analyzed. In the placebo group, there was a significant increase in the ischemic threshold during the second and third test and a significant decrease in the maximum adjusted STD during the second test which was lost during the third test. This apparent adaptation to exercise-induced ischemia was not seen in the glibenclamide-treated patients. In the pinacidil-treated patients, there was a paradoxical decrease in ischemic threshold during the second test with no change in maximum adjusted STD which tended to be lower than in the placebo-treated patients on each exercise test. This study confirms that the warm-up phenomenon can be induced during repeated exercise testing. The blockade of this phenomenon by glibenclamide suggests that the ATP-sensitive potassium channels may be involved in this potential protective mechanism. At the same time, the paradoxical response in the pinacidil-treated patients flags a warning that drugs acting on the sarcolemmal ATP-sensitive potassium channels may have a direct effect on the ST-segment that may interfere with the interpretation of the electrocardiogram.
Severe Encephalopathy Induced by the First but Not the Second Course of High-Dose Methotrexate Mirrored by Plasma Homocysteine Elevations and Preceded by Extreme Differences in Pretreatment Plasma Folate
Authors: Valik Dalibor , Sterba Jaroslav , Bajciova Viera , Demlova Regina
Published: September 2005

Plasma homocysteine has recently been associated with the occurrence of methotrexate-related neurotoxicity. We observed extreme elevations of homocysteine in a 9-year-old boy presenting with leukemia treated with the ALL-BFM 95 protocol. Coma occurred at about the 71st hour from the first methotrexate administration, and lasted for 30 h but MRI and CT studies showed no intracranial pathology. The second course of high-dose methotrexate was administered with no complications. Homocysteine areas under the curve (AUC) were calculated as the sum of areas of rectangles during the 6-hour intervals from T₀ to T72 hours (AUC0–72) and methotrexate AUCs were evaluated using MW/PHARM3.3 software. The AUC of homocysteine during the first, toxic course was 5.2 times higher than AUC during the second administration, whereas AUC of methotrexate also differed by a factor of 5. Plasma concentrations of folate prior to the first and the second courses, respectively, were 4.4 versus 45 µmol/l making this difference the most striking discriminator between the two courses. Mutation analysis showed that the patient was heterozygous for the C677T mutation in the MTHFR gene. We suggest that plasma homocysteine, pretreatment plasma folate and possibly the presence of MTHFR mutations may be biomarkers of methotrexate toxicity and possibly its antifolate effect targeted towards the tumor as well.
Evaluation of Interaction between Intrathecal Adenosine and MK801 or NBQX in a Rat Formalin Pain Model
Authors: Yoon Myung Ha , Bae Hong Beom , Choi Jeong Il , Jeong Seong Wook , Chung Sung Su , Yoo Kyung Yeon , Jeong Chang Young , Kim Seok Jae , Chung Sung Tae , Kim Chang Mo , An Tae Hun
Published: September 2005

Adenosine and excitatory amino acids have been known to be involved in modulating nociceptive transmission at the spinal level. The authors assessed the characteristics of the interaction of the adenosine-excitatory amino acid antagonist combinations in the spinal cord of rats on the formalin-induced nociception. Intrathecal NMDA antagonist ((5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a[,]d]cyclohepten-5,10-imine hydrogen maleate, MK801, 30 µg) and AMPA antagonist (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[F]quinoxaline-7-sulfonamide, NBQX, 3 µg) decreased the total number of flinches during both phases in the formalin test. Intrathecal adenosine (300 µg) had little effect on the phase 1 flinching response, but decreased the phase 2 response. The fixed dose analysis and the isobolographic analysis revealed that adenosine interacts additively with MK801 and NBQX in the spinal cord.
Short-Term Growth after Withdrawal of Exogenous Glucocorticoids
Authors: Wolthers Ole D. , Schou Anders J.
Published: September 2005

Background: The growth-suppressive effect of systemic glucocorticoids in children is well established, however, recovery of growth after withdrawal of short-term treatment in school-age children has not been evaluated. Objective: To assess short-term growth after withdrawal of systemic glucocorticoids. Methods: A post-hoc analysis of data from a double-blind lower leg growth trial which compared 5 mg prednisolone once daily in the evening with placebo was performed. The study consisted of run-in, treatment, wash-out and run-out periods of 1 week duration. In 10 children with asthma (mean age 11 years) lower leg growth measured with the knemometer could be studied up to 3 weeks after withdrawal of prednisolone. Results: Mean (SEM) lower leg growth rates during run-in, prednisolone treatment and the first, second and third weeks after withdrawal of prednisolone were 0.48 (0.15), –0.27 (0.20), 0.53 (0.19), 0.72 (0.16) and 0.66 (0.14) mm/week, p < 0.001. Mean growth rates during run-in and the first, second and third weeks after withdrawal of prednisolone did not vary, p = 0.68. Conclusion: Recovery of suppressed lower leg growth rates occurs within a week after withdrawal of exogenous glucocorticoids.
Use of Long-Term Microdialysis Subcutaneous Glucose Monitoring in the Management of Neonatal Diabetes
Authors: Holzinger Andreas , Bonfig Walter , Kusser Beate , Eggermann Thomas , Müller Herbert , Münch Hans-Georg
Published: September 2005

In neonatal diabetes mellitus (NDM), a rare genetic disorder, insulin therapy is required but the management is difficult. Frequent blood glucose determinations are necessary in most cases. Microdialysis subcutaneous glucose monitoring (MSGM) is feasible in neonates and has been proposed to reduce painful blood sampling and blood loss. We have applied long-term MSGM to a small-for-date female newborn with transient NDM. We found a good correlation of subcutaneous and blood glucose concentration over a wide range of values. MSGM enabled a reduction in blood glucose determinations during optimization of intravenous insulin treatment and initiation of continuous subcutaneous insulin infusion. We conclude that long-term MSGM is feasible and may reduce painful blood sampling and blood loss in NDM. Furthermore, long-term MSGM may hold a potential for avoiding hypoglycemic episodes and earlier discharge.
Statin Protects Endothelial Nitric Oxide Synthase Activity in Hypoxia-Induced Pulmonary Hypertension
Authors: Murata Takahisa , Kinoshita Kazuya , Hori Masatoshi , Kuwahara Masayoshi , Tsubone Hirokazu , Karaki Hideaki , Ozaki Hiroshi
Published: September 2005

Objective—

We investigated the effects of fluvastatin on hypoxia-induced (1 to 3 weeks, 10% O
2
) pulmonary hypertension with focus on endothelial nitric oxide synthase (eNOS) activity.

Methods and Results—

Oral fluvastatin treatment (1 mg/kg daily) prevented the causing and progression of pulmonary hypertension as determined by the right ventricular pressure, right ventricular hypertrophy, and muscularization of pulmonary artery. We also revealed that fluvastatin treatments prevented the hypoxia-induced decrease in cGMP production in the rat lung and restored the endothelium-dependent relaxation in the pulmonary artery. We revealed that this beneficial effect was not dependent on the increase in eNOS mRNA or protein expression, but was dependent on the inhibition of the eNOS-tight coupling with caveolin-1, the eNOS dissociation from heat shock protein 90, and the decrease in eNOS Ser
1177
–phosphorylation induced by hypoxia. Furthermore, in a whole-mount immunostaining the hypoxia-induced eNOS protein condensation with caveolin-1 of pulmonary endothelial cells was restored by the fluvastatin-treatment.

Conclusion—

These results suggest that the fluvastatin exerts beneficial effects on chronic hypoxia-induced pulmonary hypertension by protecting against the eNOS activity at the post-transcriptional level.
Angiotensin-Converting Enzyme Inhibition Increases Basal Vascular Tissue Plasminogen Activator Release in Women But Not in Men
Authors: Pretorius Mias , Luther James M. , Murphey Laine J. , Vaughan Douglas E. , Brown Nancy J.
Published: September 2005

Objective—Angiotensin-converting enzyme inhibition (ACEI) increases vascular tissue plasminogen activator (t-PA) release through endogenous bradykinin (BK). We tested the hypothesis that gender influences the effect of ACEI on t-PA release.

Methods and Results—We measured the effect of intra-arterial enalaprilat (0.33 μg/min per 100 mL forearm volume) on forearm blood flow (FBF) and net t-PA release before and during BK (25 to 400 ng/min) and methacholine (3.2 to 12.8 μg/min) in premenopausal women, postmenopausal women not using hormone replacement, young men, and older men. Baseline net t-PA release was similar among groups. Enalaprilat increased basal t-PA release in premenopausal (from 0.9±1.0 to 5.1±1.7 ng/min per 100 mL,P=0.023) and postmenopausal women (from −3.9±2.2 to 3.9±1.1 ng/min per 100 mL,P=0.010) but not in young or older men (P=0.028 men versus women). Enalaprilat potentiated the effect of exogenous BK on FBF similarly in all groups. However, during enalaprilat, BK-stimulated t-PA release was greatest in premenopausal women (339.9±86.4 ng/min per 100 mL at the 100 ng/min dose,P<0.05 versus any other group), intermediate in postmenopausal women (243.8±51.1 ng/min per 100 mL,P<0.05 versus either male group), and least in young (111.9±19.2 ng/min/100 mL) and older men (103.4±27.6 ng/min/100 mL).

Conclusion—ACEI enhances basal t-PA release in women, independent of menopausal status, but not in men. During ACEI, both gender and menopausal status affect BK stimulated t-PA release.
Apolipoprotein A-V Deficiency Results in Marked Hypertriglyceridemia Attributable to Decreased Lipolysis of Triglyceride-Rich Lipoproteins and Removal of Their Remnants
Authors: Grosskopf Itamar , Baroukh Nadine , Lee Sung-Joon , Kamari Yehuda , Harats Dror , Rubin Edward M. , Pennacchio Len A. , Cooper Allen D.
Published: September 2005

Objective—

ApoAV, a newly discovered apoprotein, affects plasma triglyceride level. To determine how this occurs, we studied triglyceride-rich lipoprotein (TRL) metabolism in mice deficient in apoAV.

Methods and Results—

No significant difference in triglyceride production rate was found between

apoa5
−/−

mice and controls. The presence or absence of apoAV affected TRL catabolism. After the injection of
14
C-palmitate and
3
H-cholesterol labeled chylomicrons and
125
I-labeled chylomicron remnants, the disappearance of
14
C,
3
H, and
125
I was significantly slower in
apoa5
−/−
mice relative to controls. This was because of diminished lipolysis of TRL and the reduced rate of uptake of their remnants in

apoa5
−/−

mice. Observed elevated cholesterol level was caused by increased high-density lipoprotein (HDL) cholesterol in

apoa5
−/−

mice. VLDL from
apoa5
−/−
mice were poor substrate for lipoprotein lipase, and did not bind to the low-density lipoprotein (LDL) receptor as well as normal very-low-density lipoprotein (VLDL). LDL receptor levels were slightly elevated in

apoa5
−/−

mice consistent with lower remnant uptake rates. These alterations may be the result of the lower apoE-to-apoC ratio found in VLDL isolated from
apoa5
−/−
mice.

Conclusions—

These results support the hypothesis that the absence of apoAV slows lipolysis of TRL and the removal of their remnants by regulating their apoproteins content after secretion.
Fast Food, Central Nervous System Insulin Resistance, and Obesity
Authors: Isganaitis Elvira , Lustig Robert H.
Published: September 2005

Rates of obesity and insulin resistance have climbed sharply over the past 30 years. These epidemics are temporally related to a dramatic rise in consumption of fast food; until recently, it was not known whether the fast food was driving the obesity, or vice versa. We review the unique properties of fast food that make it the ideal obesigenic foodstuff, and elucidate the mechanisms by which fast food intake contributes to obesity, emphasizing its effects on energy metabolism and on the central regulation of appetite. After examining the epidemiology of fast food consumption, obesity, and insulin resistance, we review insulin’s role in the central nervous system’s (CNS) regulation of energy balance, and demonstrate the role of CNS insulin resistance as a cause of leptin resistance and in the promotion of the pleasurable or “hedonic” responses to food. Finally, we analyze the characteristics of fast food, including high-energy density, high fat, high fructose, low fiber, and low dairy intake, which favor the development of CNS insulin resistance and obesity.
Importance of Early Ischemic Computed Tomography Changes Using ASPECTS in NINDS rtPA Stroke Study
Authors: Demchuk Andrew M. , Hill Michael D. , Barber Philip A. , Silver Brian , Patel Suresh C. , Levine Steven R.
Published: September 2005

Background and Purpose—

The importance of early ischemic change (EIC) on baseline computed tomography (CT) in the decision to thrombolyze the patient with acute ischemic stroke has been controversial. ASPECTS is a semiquantitative scale that scores the extent of EIC within the middle cerebral artery territory. We examined whether ASPECTS could be a treatment modifier by systematically reviewing the CT scans in the NINDS rtPA Stroke Study.

Methods—

Six hundred eight of the 624 CT scans were available and of sufficient quality. One of 2 teams (n=3 each) of expert ASPECTS readers evaluated each scan for an ASPECTS value using a consensus score approach. Each team was blind to all clinical information except symptom side and blind to follow-up imaging and outcome information. ASPECTS values were stratified before analysis. Multivariable logistic regression was used to determine if an ASPECTS by treatment interaction existed on treatment response, outcome, and intracerebral hemorrhage risk.

Results—

A total of 57.2% (348 of 608) of scans showed EIC with an ASPECTS <10. ASPECTS dichotomized into 8 to 10 and <8 did not have a treatment-modifying effect on good outcome but showed a trend to lower mortality at 90 days with tPA (relative risk 0.67, 95% confidence interval 0.41 to 1.06,
P
=0.10). ASPECTS 8 to 10 were associated with a trend to larger benefit of tPA with a number needed to treat (NNT) of 5 versus ASPECTS 3 to 7 with a NNT of 8.

Conclusion—

There was no evidence of treatment effect modification by the baseline ASPECTS value in the NINDS rtPA Stroke Study. Therefore, exclusion of patients for thrombolysis within 3 hours of symptom onset based on EIC is not supported by our data. There is a trend to reduced mortality and increased benefit to rtPA if the baseline CT scan is favorable (ASPECTS >7).
Effect of Posture on the Perception of Verticality in Neglect Patients
Authors: Saj Arnaud , Honoré Jacques , Davroux Jessy , Coello Yann , Rousseaux Marc
Published: September 2005

Background and Purpose—

The anticlockwise (ACW) deviation of the visual and visuohaptic subjective verticals (SVs), known to occur in patients with right hemisphere lesion, is amplified by spatial neglect (N). These patients have only been assessed when sitting. We investigated the hypothesis that postural changes modulate visuohaptic SV deviation.

Methods—

Eight patients presenting with a right hemisphere lesion and spatial N were compared with 6 matched control subjects (C). In the dark, they had to rotate a luminous rod to put it at the vertical in 4 conditions: (1) sitting with plantar sole support; (2) sitting without plantar sole support; (3) sitting with legs extended on a support; and (4) supine position.

Results—

N patients showed a significant ACW deviation (−4.5°) of the SV compared with C subjects (+0.01°). The effect of body position depended on the group (
P
=0.022) because changes had definite effects in the N but not in the C group. In fact, the former showed a reduction of the ACW deviation, from the first to the fourth condition.

Conclusions—

Although the possible role of plantar and leg somaesthetic inputs remains to be thoroughly investigated, the modulation of gravitational inputs at trunk or vestibular level influences the SV deviation in N patients. This has to be put in relation with the modulation of N signs reported by other authors when passing from the sitting to the supine position.
One-Stage Anterior Approach for Four-Vessel Occlusion in Rat
Authors: Yamaguchi Mitsuo , Calvert John W. , Kusaka Gen , Zhang John H.
Published: September 2005

Background and Purpose—

We report a modified 4-vessel occlusion (4VO) rat model.

Method—

We used a 1-stage anterior approach for making bilateral hemispheric ischemia.

Results—

Modified 4VO method decreased cerebral blood flow to 12% to 14% of baseline levels.

Conclusion—

This modified 4VO method is a minimally invasive, quick, reliable procedure for producing ischemic changes.
Edaravone Reduces Early Accumulation of Oxidative Products and Sequential Inflammatory Responses After Transient Focal Ischemia in Mice Brain
Authors: Zhang Ning , Komine-Kobayashi Miki , Tanaka Ryota , Liu Meizi , Mizuno Yoshikuni , Urabe Takao
Published: September 2005

Background and Purpose—

Oxidative stress contributes to ischemia/reperfusion neuronal damage in a consecutive 2-phase pattern: an immediate direct cytotoxic effect and subsequent redox-mediated inflammatory insult. The present study was designed to assess the neuroprotective mechanisms of edaravone, a novel free radical scavenger, through antioxidative and anti-inflammatory pathways, from the early period to up to 7 days after ischemia/reperfusion in mice.

Methods—

Mice were subjected to 60-minute ischemia followed by reperfusion. They were divided into the edaravone group (n=72; with different schedules for first administration) and the vehicle (control) group (n=36). Infarct volume and neurological deficit scores were evaluated at several time points after ischemia. Immunohistochemical analysis for 4-hydroxy-2-nonenal (HNE), 8-hydroxy-deoxyguanosine (8-OHdG), ionized calcium-binding adapter molecule 1 (Iba-1), inducible NO synthase (iNOS), and nitrotyrosine were performed at 24 hours, 72 hours, or 7 days after reperfusion.

Result—

Edaravone, even when administrated 6 hours after onset of ischemia/reperfusion, significantly reduced the infarct volume (68.10±6.24%;
P
<0.05) and improved the neurological deficit scores (
P
<0.05) at 24 hours after reperfusion. Edaravone markedly suppressed the accumulation of HNE-modified protein and 8-OHdG at the penumbra area during the early period after reperfusion (
P
<0.05) and reduced microglial activation, iNOS expression, and nitrotyrosine formation at the late period.

Conclusion—

Our results indicated that edaravone exerts an early neuroprotective effect through the early free radicals scavenging pathway and a late anti-inflammatory effect and suggested that edaravone is important for expansion of the therapeutic time window in stroke patients.
The Link between Social Cognition and Self-referential Thought in the Medial Prefrontal Cortex
Authors: Mitchell Jason P. , Banaji Mahzarin R. , Macrae C. Neil
Published: September 2005

The medial prefrontal cortex (mPFC) has been implicated in seemingly disparate cognitive functions, such as understanding the minds of other people and processing information about the self. This functional overlap would be expected if humans use their own experiences to infer the mental states of others, a basic postulate of simulation theory. Neural activity was measured while participants attended to either the mental or physical aspects of a series of other people. To permit a test of simulation theory's prediction that inferences based on self-reflection should only be made for similar others, targets were subsequently rated for their degree of similarity to self. Parametric analyses revealed a region of the ventral mPFC—previously implicated in self-referencing tasks—in which activity correlated with perceived self/other similarity, but only for mentalizing trials. These results suggest that self-reflection may be used to infer the mental states of others when they are sufficiently similar to self.
The Tale of Those Who Did Not Travel: Reading Yahyā al-Tāhir 'Abdullah's The Neckband and the Bracelets As Sīrah
Authors: Yaqub Nadia
Published: September 2005

In The Neckband and the Bracelet, Yahyā al-Tāhir 'Abdullah uses allusion, reference, imagery, and narrative techniques borrowed from the popular Arabic sīrah to portray characters who are imprisoned in a harsh world that suppresses their human individuality and molds them into character types. By invoking, imitating, and inverting sīrah time in the modern novel and juxtaposing a complete and unchanging epic world view against a backdrop of historical and social change, 'Abdullah succeeds in telling an eloquent tale about the suppression of human potential.
Women Narrating the Gulf: A Gulf of Their Own
Authors: Driss Hager Ben
Published: September 2005

Starting from the premise that space is a purveyor of discourse, this article attempts to probe the work of three women writers narrating the Gulf. The Kuwaiti Laylā al-'Uthmān, the Saudi Arabian Rajā' 'Ālim and the Iraqi Hadiyya Husayn write the spaces to which they belong within representational modes speci fic to each region. The conservative Kuwaiti society and the holy land of Saudi Arabia generate strategies of camou flage including humor, pardoy, and allegory. The bloody history of Iraq, especially during the second half of the twentieth century, yields a subversive confessional mood and a dominating atmosphere of pain. While diverging in tone and narrative strategies, these three women writers converge in presenting a Gulf of their own: a personalized landscape wherein the physical world overlaps with psychological scenes. These writers also succeed in bridging the gap between the private and public and offer narratives in which the personal is relocated in the political, cultural, and historical.
Investigation of Vertical and Horizontal Momentum Transfer in the Gulf of Mexico Using Empirical Mode Decomposition Method
Authors: Lai Ronald J. , Huang Norden
Published: September 2005

Data from a series of deep mooring stations in the Gulf of Mexico (GOM) have been analyzed with the newly developed empirical mode decomposition and Hilbert spectral analysis method, abbreviated as Hilbert–Huang transformation (HHT). The flows in the GOM near the shelf/slope region are treated as a two-layer system, with the 800-m permanent thermocline as the dividing depth. When the data are treated with HHT, motions of different temporal scales are identified. The top layer (depth less than 800 m) is controlled by inertia flow with episodic Loop Current eddies, while the lower layer (depth greater than 800 m) is controlled primarily by the topographic Rossby waves and small-scale cyclonic and anticyclonic eddies. Using a cross-correlation analysis between the appropriate intrinsic mode components from the data, the wavelength, the phase velocity, and the vertical trapping depth for the topographic Rossby waves were determined. Observations are in general agreement with the modeled results by Oey and Lee.