bluuebunny/crossref_metadata_2025 huggingface dataset:
Gonadectomy prevents endothelial dysfunction in fructose-fed male rats, a factor contributing to the development of hypertension
Authors: Vasudevan Harish , Nagareddy Prabhakara Reddy , McNeill John H.
Published: July 2006

Insulin resistance has been shown to be associated with increased blood pressure (BP). The sex hormones estrogen and testosterone have opposing effects in the development of increased BP. Since testosterone has been implicated in increased BP following insulin resistance, we have tried to dissect out the effects of insulin resistance on endothelium-dependent vasorelaxation in the presence and absence of testosterone. Both gonadectomized and sham-operated male Wistar rats fed with a high-fructose diet developed insulin resistance, but BP increased only in the sham-operated rats. Reintroduction of testosterone in vivo restored the increase in BP, thereby abolishing the protective effects of gonadectomy. Fructose feeding did not affect plasma testosterone levels. Insulin resistance induced endothelial dysfunction in the mesenteric arteries of sham-operated rats, which was prevented by gonadectomy, thus suggesting a key role for testosterone in the pathogenesis of secondary vascular complications. Subsequent to blocking the actions of endothelium-dependent hyperpolarizing factor (EDHF), relaxation to acetylcholine (ACh) was lower in sham-operated fructose-fed rats compared with other groups, suggesting the involvement of nitric oxide (NO) in vasorelaxation. Inhibition of NO synthesis nearly abolished the ACh-evoked relaxation in both fructose-fed groups, thus suggesting a testosterone-independent impairment of EDHF-mediated relaxation. The improvement in endothelial function following gonadectomy could be ascribed to a NO component, although plasma nitrite and nitrate levels were unchanged. In summary, testosterone is essential in vivo for the development of endothelial dysfunction and hypertension secondary to insulin resistance, suggesting a facilitatory role for testosterone in increasing BP in fructose-fed male rats.
Dissociation between alveolar transmigration of neutrophils and lung injury in hyperoxia
Authors: Perkowski Sandra , Scherpereel Arnaud , Murciano Juan-Carlos , Arguiri Evguenia , Solomides Charalambos C. , Albelda Steven M. , Muzykantov Vladimir , Christofidou-Solomidou Melpo
Published: July 2006

The objective of this study was to quantitatively assess changes in cell adhesion molecule (CAM) expression on the pulmonary endothelial surface during hyperoxia and to assess the functional significance of those changes on cellular trafficking and development of oxygen-induced lung injury. Mice were placed in >95% O2for 0–72 h, and pulmonary injury and neutrophil (PMN) sequestration were assessed. Specific pulmonary CAM expression was quantified with a dual-radiolabeled MAb technique. To test the role of CAMs in PMN trafficking during hyperoxia, blocking MAbs to murine P-selectin, ICAM-1, or platelet-endothelial cell adhesion molecule-1 (PECAM-1) were injected in wild-type mice. Mice genetically deficient in these CAMs and PMN-depleted mice were also evaluated. PMN sequestration occurred within 8 h of hyperoxia, although alveolar emigration occurred later (between 48 and 72 h), coincident with rapid escalation of the lung injury. Hyperoxia significantly increased pulmonary uptake of radiolabeled antibodies to P-selectin, ICAM-1, and PECAM-1, reflecting an increase in their level on pulmonary endothelium and possibly sequestered blood cells. Although both anti-PECAM-1 and anti-ICAM-1 antibodies suppressed PMN alveolar influx in wild-type mice, only mice genetically deficient in PECAM-1 showed PMN influx suppression. Neither CAM blockade, nor genetic deficiency, nor PMN depletion attenuated lung injury. We conclude that early pulmonary PMN retention during hyperoxia is not temporally associated with an increase in endothelial CAMs; however, subsequent PMN emigration into the alveolar space may be supported by PECAM-1 and ICAM-1. Blocking PMN recruitment did not prevent lung injury, supporting dissociation between PMN infiltration and lung injury during hyperoxia in mice.
Isoprostane-induced airway hyperresponsiveness is dependent on internal Ca2+ handling and Rho/ROCK signaling
Authors: Liu Caiqiong , Tazzeo Tracy , Janssen Luke J.
Published: July 2006

We previously reported the ability of isoprostanes to induce airway hyperresponsiveness (AHR). In this study, we examined the signaling mechanisms underlying that phenomenon with the standard muscle bath technique. Responses to a threshold concentration of carbachol (CCh, 3 × 10−9 M) were significantly augmented by pretreatment for 20 min with 8-isoprostaglandin E2 (15-E2t-IsoP, 10−6 M): this AHR was obliterated in tissues pretreated with the selective Rho kinase (ROCK) inhibitor Y-27632 added 20 min before isoprostane, but not by cyclopiazonic acid (CPA). Increasing the CCh concentration to 3 × 10−8 M (still considerably less than the half-maximally effective concentration of CCh) evoked larger contractions that were also augmented significantly by 15-E2t-IsoP: this AHR was completely abolished in tissues pretreated with CPA as well as those pretreated with Y-27632. We noted, however, that Y-27632 and CPA profoundly effect baseline tone and the cholinergic response per se, which confounds the interpretation of the data summarized above. We therefore modified the protocol by using combinations of CCh and blocker (CPA, Y-27632, or nifedipine) that were equieffective. In this way, we found that AHR could not be demonstrated under conditions in which Rho/ROCK signaling or Ca2+ release was abolished (by Y-27632 and CPA, respectively). Likewise, other autacoids that act through G protein-coupled receptors via Rho/ROCK and Ca2+ release (serotonin, histamine) mimicked this effect of isoprostane, whereas bradykinin did not. We conclude that isoprostane-induced AHR is mediated in part through an action on Rho/ROCK signaling. This novel finding may contribute to a better understanding of the mechanisms underlying AHR and asthma.
Alveolar fluid reabsorption is increased in rats with compensated heart failure
Authors: Azzam Zaher S. , Adir Yochai , Welch Lynn , Chen Jiwang , Winaver Joseph , Factor Phillip , Krivoy Norberto , Hoffman Aaron , Sznajder Jacob I. , Abassi Zaid
Published: July 2006

Alveolar fluid reabsorption (AFR) is important in keeping the air spaces free of edema. This process is accomplished via active transport of Na+across the alveolo-capillary barrier mostly by apical Na+channels and basolateral Na+-K+-ATPases. Recently, we have reported that acute elevation of left atrial pressures is associated with decreased AFR in isolated rat lungs. However, the effect of chronic elevation of pulmonary capillary pressure, such as seen in patients with congestive heart failure (CHF), on AFR is unknown. CHF was induced by creating an aorto-caval fistula (ACF) in Sprague-Dawley male rats. Seven days after the placement of the fistula, AFR was studied in the isolated perfused rat lung model. AFR in control rats was 0.49 ± 0.02 ml/h (all values are means ± SE) and increased by ∼40% (0.69 ± 0.03 ml/h) in rats with chronic CHF ( P < 0.001). The albumin flux from the pulmonary circulation into the air spaces did not increase in the experimental groups, indicating that lung permeability for large solutes was not increased. Na+-K+-ATPase activity and protein abundance at the plasma membrane of distal alveolar epithelial tissue were significantly increased in CHF rats compared with controls. These changes were associated with increased plasma norepinephrine levels in CHF rats compared with controls. We provide evidence that in a rat model of chronic compensated CHF, AFR is increased, possibly due to increased endogenous norepinephrine upregulating active sodium transport and protecting against alveolar flooding.
Identification of a hydrogen peroxide-induced PP1-JNK1-Sp1 signaling pathway for gene regulation
Authors: Chu Shijian , Ferro Thomas J.
Published: July 2006

Oxidative stress often results in changes in gene expression through the regulation of transcription factors. In this study, we examine how Sp1 phosphorylation is regulated by H2O2 in a human alveolar epithelial cell line (HAE). Treatment of HAE cells with H2O2 increases phosphorylation of Sp1 and activates JNK. To establish a relationship between JNK and Sp1, we show that JNK activator anisomycin increases Sp1 phosphorylation, and JNK inhibitors as well as dominant-negative JNK1 attenuate H2O2-induced Sp1 phosphorylation. Additionally, JNK1 directly phosphorylates Sp1 in vitro, reducing Sp1 binding to DNA. These results demonstrate the role of JNK in H2O2-induced Sp1 phosphorylation. Because H2O2 inhibits Ser/Thr protein phosphatase-1 (PP1), we examined the role of PP1 in the regulation of JNK. Similar to H2O2, inhibition of PP1 induces phosphorylation of Sp1 and activation of JNK in HAE cells. Inhibition of JNK activity using either inhibitors or dominant-negative mutant JNK1 suppresses PP1 inhibition-induced Sp1 phosphorylation. Furthermore, PP1 directly inactivates JNK1 in vitro. These data suggest that 1) H2O2 increases the phosphorylation level of Sp1, 2) Sp1 is a target of the JNK pathway, 3) PP1 regulates JNK activation, and 4) the “PP1-JNK” pathway plays a role in H2O2-induced Sp1 phosphorylation in lung epithelial cells.
Cholecystokinin and Gastrin Receptors
Authors: Dufresne Marlène , Seva Catherine , Fourmy Daniel
Published: June 2006

Cholecystokinin and gastrin receptors (CCK1R and CCK2R) are G protein-coupled receptors that have been the subject of intensive research in the last 10 years with corresponding advances in the understanding of their functioning and physiology. In this review, we first describe general properties of the receptors, such as the different signaling pathways used to exert short- and long-term effects and the structural data that explain their binding properties, activation, and regulation. We then focus on peripheral cholecystokinin receptors by describing their tissue distribution and physiological actions. Finally, pathophysiological peripheral actions of cholecystokinin receptors and their relevance in clinical disorders are reviewed.
Spike Timing-Dependent Plasticity: From Synapse to Perception
Authors: Dan Yang , Poo Mu-Ming
Published: June 2006

Information in the nervous system may be carried by both the rate and timing of neuronal spikes. Recent findings of spike timing-dependent plasticity (STDP) have fueled the interest in the potential roles of spike timing in processing and storage of information in neural circuits. Induction of long-term potentiation (LTP) and long-term depression (LTD) in a variety of in vitro and in vivo systems has been shown to depend on the temporal order of pre- and postsynaptic spiking. Spike timing-dependent modification of neuronal excitability and dendritic integration was also observed. Such STDP at the synaptic and cellular level is likely to play important roles in activity-induced functional changes in neuronal receptive fields and human perception.
CFH Gene Variant, Y402H, and Smoking, Body Mass Index, Environmental Associations with Advanced Age-Related Macular Degeneration
Authors: Seddon Johanna M. , George Sarah , Rosner Bernard , Klein Michael L.
Published: July 2006

Objectives: We tested the hypothesis that modifiable lifestyle factors alter the genetic susceptibility associated with a common coding variant in the complement factor H (CFH) gene, Y402H, for the leading cause of blindness among the elderly, age-related macular degeneration (AMD). Methods: In this case-control association analysis, Caucasian participants in the multicenter Age-Related Eye Disease Study with advanced AMD (n = 574 cases) or no AMD (n = 280 controls) were evaluated. AMD status was determined by grading of fundus photographs. Risk factors including cigarette smoking and body mass index (BMI) were assessed and DNA specimens were genotyped for the variant in the CFH gene. Unconditional logistic regression analyses were performed. Attributable risks and multivariable AMD risk scores were calculated. Results: The number of risk alleles for Y402H was associated with advanced AMD, with odds ratios (OR) of 2.7 (95% confidence interval (CI) 1.8–3.8) for the CT heterozygous genotype and OR 7.4 (4.7–11.8) for the homozygous CC risk genotype, after controlling for demographic and behavioral risk factors. Current cigarette smoking (OR 5.1) and high BMI ≧30 (OR 2.1) were independently related to AMD, controlling for genotype. The association between AMD and BMI varied dependent on genotype (P interaction = 0.006 for the CT vs. TT genotype). The CC genotype plus higher BMI (OR 5.9) or smoking (OR 10.2) conferred the greatest risks. Gene plus environment risk scores provided an area under the receiver operating characteristic (ROC) curve of 0.70–0.75. Conclusions: Genetic and environmental factors are independently related to advanced AMD, and modifiable factors alter genetic susceptibility. The AMD risk score identifies a highly susceptible population.
Oxidative Stress in Vero Cells Infected with Vesicular Stomatitis Virus
Authors: Riva Diego A. , Ríos de Molina María C. , Rocchetta Iara , Gerhardt Elizabeth , Coulombié Félix C. , Mersich Susana E.
Published: July 2006

Viral-induced apoptosis might be mediated by oxidative stress. It has already been described that cell death in vesicular stomatitis virus (VSV)-infected cells occurs by apoptosis. In this study, oxidative stress parameters present in VSV-infected Vero cells were analyzed. Lipid peroxides (LP) were evaluated in cellular extracts and expressed as thiobarbituric acid-reactive substances. LP levels exhibited a rise at different times post infection, according to the multiplicity of infection (MOI), while the presence of cycloheximide determined a reduction on LP. Also, an increase in protein degradation products and a decrease in polyunsaturated fatty acids content was observed, indicating that cellular proteins and lipids began to be susceptible to degradation during VSV infection. In addition, we analyzed cell viability of VSV-infected Vero cells, which were incubated in the presence of butylated hydroxyanisole. This antioxidant was able to protect Vero cells, at least at MOIs assayed in this study, and to reduce viral yield only when VSV infection was done at MOI 0.05. Further, superoxide dismutases, which occupy the first step within the antioxidant enzyme cascade, also exhibit a rise in VSV-infected Vero cells, at different MOI. These results suggest that both an oxidative stress and an antioxidative cell response precede the induction of apoptosis by VSV.
Enhanced Induction of SARS-CoV Nucleocapsid Protein-Specific Immune Response Using DNA Vaccination followed by Adenovirus Boosting in BALB/c Mice
Authors: Chunling Ma , Kun Yao , Jian Xu , Jian Qin , Hua Sun , Minsheng Zhu
Published: July 2006

Objective: To investigate immunogenicity in the induction of humoral and cellular immune responses to genetic vaccines of the recombinant severe acute respiratory syndrome-associated coronavirus (SARS-CoV)-N gene expressing the same protein plasmid, pcDNA3.1-N, and replication-defective adenoviral vector, rAd-N, in a pcDNA3.1-N prime-rAd-N boost regimen and the reverse sequence in a rAd-N prime-pcDNA3.1-N boost regimen. Method: After the mice had been immunized intramuscularly and/or intraperitoneally with pcDNA3.1-N and rAd-N in prime-triple boost immunization, humoral and cellular immune responses were detected. Results: After detection, different levels of anti-N humoral and cellular responses are shown compared to controls. The humoral immune response was induced more effectively by the DNA priming and recombinant adenovirus boosting regimen and the reverse sequence of heterogeneous combinations. There is a significant difference between heterogeneous and homologous vaccinations. However, the cytotoxic T lymphocyte (CTL) response was not significantly altered by the different prime-boost immunizations or the recombinant adenovirus of pcDNA3.1-N prime-rAd-N boost regimen alone, but lymphoproliferation and interferon-γ (IFN-γ) secretion were all enhanced by heterologous combination immunizations compared to homologous combinations. For the reverse sequence immunization regimen, lymphoproliferation, IFN-γ and CTL responses were all significantly weaker compared with pcDNA3.1-N prime-rAd-N boost regimen. Conclusion: Taken together, of all the combinations, the prime-triple boost immunization of pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N/rAd-N can effectively induce SARS-CoV-N-specific and strong humoral and cellular immune responses in mice. The present results suggest that DNA immunization followed by recombinant adenovirus boosting could be used as a potential SARS-CoV vaccine in the induction of an enhanced humoral and cellular immune response.
The Effects of a Mixture of Brown and Black Rice on Lipid Profiles and Antioxidant Status in Rats
Authors: Kim Jung Yun , Do Min Hee , Lee Sang Sun
Published: July 2006

Background: The present study was designed to investigate the influence of natural brown and black rice consumption on serum lipid parameters and hepatic enzyme activities in rats fed different combinations of grains. Methods: 50 male rats were divided into 4 groups and raised for 8 weeks on diets containing white rice (WH), white rice and brown rice (WHBR), white rice and black rice (WHBL), brown rice and black rice (BRBL). Blood samples were collected for lipid measurements, and the oxidant and antioxidant status of liver was evaluated. Results: Plasma triglyceride, total cholesterol and low-density lipoprotein cholesterol in rats fed the WH diet were higher than in other groups. High-density lipoprotein cholesterol was significantly higher in rats fed diets including black rice such as WHBL and BRBL compared with WH and WHBR. The level of thiobarbituric acid reactive substances in liver is shown to be higher in rats in the order of those fed WH, WHBR, WHBL and BRBL. While superoxide dismutase and chloramphenicol acetyltransferase did not differ among the 4 groups, glutathione and glutathione peroxidase in WH were significantly lower than in other groups. Conclusion: This study demonstrates that brown and black rice have cardioprotective effects.
Influence of ALA54THR Polymorphism of Fatty Acid Binding Protein 2 on Lifestyle Modification Response in Obese Subjects
Authors: de Luis D.A. , Aller R. , Izaola O. , Gonzalez Sagrado M. , Conde R.
Published: July 2006

Background/Aim: It has been found that the expression of fatty acid binding protein 2 (FABP2) mRNA is under dietary control. A G-to-A transition at codon 54 of FABP2 results in an amino acid substitution (from Ala 54 to Thr 54). This polymorphism was associated with high insulin resistance and high fasting insulin concentrations. The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 protein on the response to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients. Methods: A population of 69 obese (body mass index >30) nondiabetic outpatients was analyzed in a prospective way. Before and after 3 months of the lifestyle modification program, indirect calorimetry, tetrapolar electrical bioimpedance measurement, blood pressure recording, serial assessment of the nutritional intake (3 days of written food records), and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1,520 kcal; 52% carbohydrates, 25% lipids, and 23% proteins). The exercise program consisted of aerobic exercise for at least three times/week (60 min each). Statistical analysis was performed for combined Ala54/Thr54 and Thr54/Thr54 as a mutant group and wild-type Ala54/Ala54 as second group. Results: The mean age was 45.5 ± 16.7 years, the mean body mass index was 34.1 ± 5.1, and there were 14 males (20.3%) and 55 females (79.7%) with a weight loss of 3.17 ± 3.5 kg (3.5%). Thirty-seven patients (53.6%) had the genotype Ala54/Ala54 (wild-type group) and 32 (46.4%) patients either the genotype Ala54/Thr54 (26 patients, 30.2%) or the genotype Thr54/Thr54 (6 patients, 16.2%). The percentage of responders (weight loss) was similar in both groups (89.2 vs. 90.6%). In the wild-type group, body mass index, weight, fat mass, low-density lipoprotein cholesterol level, and waist circumference decreased, whereas the VO2 (oxygen consumption) increased. In the mutant group, glucose, body mass index, weight, waist circumference, and systolic blood pressure decreased, and VO2 increased. No differences were detected between basal values in both groups. Only the leptin levels showed a significant decrease in the wild-type group (23.85%; p < 0.05), with no statistically significant difference in the mutant group (2.59%; NS). Resistin, tumor necrosis factor alpha, interleukin 6, insulin, and C-reactive protein remained without changes in both groups. Conclusions: Weight loss is associated with different changes, depending on the FABP2 genotype. Carriers of the Thr54 allele have a different response than wild-type obese subjects, with a significant decrease of systolic blood pressure and glucose levels in Thr54 carriers and a significant decrease in fat mass, low-density lipoprotein cholesterol, and leptin in wild-type patients.
Methemoglobinemia Caused by the Ingestion of Courgette Soup Given in Order to Resolve Constipation in Two Formula-Fed Infants
Authors: Savino Francesco , Maccario Stefano , Guidi Carla , Castagno Emanuele , Farinasso Daniela , Cresi Francesco , Silvestro Leandra , Mussa Gian Carlo
Published: July 2006

Methemoglobinemia is not a rare condition arising from the exposure to hemoglobin-oxidizing agents such as nitrates-nitrites present in well water or vegetables. Infants <3 months of age are more susceptible than adults because of lower amounts of a key enzyme, NADH-cytochrome b5 reductase, which converts methemoglobin back to hemoglobin. We report 2 infants, aged respectively 2 and 1 months, suffering from methemoglobinemia, fed with a formula that was reconstituted with a high concentration of courgette soup to resolve constipation. They developed a severe cyanosis with methemoglobinemia (respectively 30.4 and 27%) and were hospitalized and treated with methylene blue at 1%. After 12 h the syndrome was completely resolved. Home-prepared infant foods containing vegetables are potential causes of methemoglobinemia. It is important not to feed infants with vegetables having a high nitrate content (e.g., courgette, spinach, beets and green beans) to resolve constipation since, particularly in the first months of life, they may cause severe methemoglobinemia.
Can Cerebrospinal Fluid Uric Acid Levels Differentiate Intraventricular Hemorrhage from Traumatic Tap?
Authors: Aliefendioğlu Didem , Gürsoy Tuğba , Hayran K. Mutlu , Aslan Ayşe Tana
Published: July 2006

Objective: To measure blood and cerebrospinal fluid (CSF) uric acid (UA) levels of neonates with intraventricular hemorrhage (IVH), and to examine whether or not UA can be used to differentiate traumatic tap from IVH. Material and Methods: The control group (n = 19, group I) consisted of neonates presenting with signs requiring analysis of CSF but whose CSF indices proved to be normal. Traumatic taps (n = 15, group II) were mimicked by adding 2 drops of homologous blood to normal CSF samples. The IVH group (n = 21, group III) consisted of neonates who had been diagnosed by cranial ultrasonography or computed tomography scans. Data are presented as median (range). Results: There was no significant difference between groups with respect to serum UA levels. While no significant difference was observed between CSF UA levels of the control [0.6 (0.1–1.8) mg/dl] and traumatic tap group [0.5 (0.3–1.1) mg/dl], the IVH group [1.6 (0.7–6.9) mg/dl] was found to have significantly higher CSF UA levels than groups I and II. Furthermore, although there were significant correlations between serum and CSF UA levels in the control and traumatic tap groups, no correlation was observed in the IVH group. Conclusion: CSF UA levels are increased in neonates with IVH and they may be used to differentiate a real hemorrhage from a traumatic tap.
Defective Expression of HRK is Associated with Promoter Methylation in Primary Central Nervous System Lymphomas
Authors: Nakamura Mitsutoshi , Ishida Eiwa , Shimada Keiji , Nakase Hiroyuki , Sakaki Toshisuke , Konishi Noboru
Published: July 2006

Objectives: Recently, it has been reported that expression of the HRK gene was significantly reduced by hypermethylation in astrocytic tumors. Our aim is to verify the alterations in the HRK gene in primary central nervous system lymphomas (PCNSLs). Methods: We analyzed the hypermethylation status and expression of the gene and 12q13.1 loss of heterozygosity in 31 PCNSLs. Results: A total of 13 PCNSLs (31%) demonstrated hypermethylation in either the promoter or exon 1; loss of HRK expression was immunohistochemically observed in 9 tumors and was significantly associated with promoter methylation. In addition, higher apoptotic counts were associated with HRK positivity. PCNSLs with HRK methylation also showed methylation of multiple genes, such as p14ARF, p16INK4a, RB1, p27Kip1 and O6-MGMT. Patients with tumors demonstrating concurrent methylation of more than half of their genes demonstrated significantly poorer survival and earlier recurrence. Hypermethylation of the HRK promoter alone was not associated with overall outcome, but relapse-free survival was significantly shorter. Conclusions: Our findings suggest that transcriptional repression of HRK is caused by promoter hypermethylation in PCNSL, and that the loss of HRK associated with the methylation profile of other genes is a potential step in the modulation of cellular death by apoptosis during PCNSL tumorigenesis.
Combined Thiersch’s Procedure and Subanodermal Coagulation for Complete Rectal Prolapse in the Elderly
Authors: Gupta Pravin J.
Published: July 2006

Background: The author describes a modification of Thiersch’s procedure in patients with complete rectal prolapse by inducing fibrosis at the anal verge through circumferential subanodermal coagulation using a radiofrequency device. Materials and Methods: An Ellman radiofrequency generator was used for coagulation. The postoperative events were recorded. The patients were followed over a period of 2 years to assess late outcome. Results: Postoperative complications were observed in 2 patients. One of these developed suppuration in the tract of the encircling wire that needed removal, while the other had a recurrence due to loosening of the wire. At a 2-year follow-up, 3 patients developed recurrence while 1 had a persistent complaint of fecal incontinence. Conclusion: This study shows that a combined procedure of radiofrequency coagulation followed by Thiersch’s circumanal wiring is quick and easy to perform with no formidable morbidity in elderly patients who are otherwise considered at high risk for definitive surgical procedures.
Results of the Combination of Open Transthoracic Esophagectomy with Laparoscopic Gastric Tube Formation for Esophageal Cancer
Authors: Cense H.A. , Busch O.R.C. , Bemelman W.A. , Obertop H. , van Lanschot J.J.B.
Published: July 2006

Background: Postoperative complications after open transthoracic esophagectomy could possibly be reduced if the abdominal phase is performed laparoscopically. The aim of this study was to investigate the feasibility of laparoscopic mobilization of the stomach and gastric tube formation in patients undergoing an open transthoracic esophagectomy for cancer. Methods: Thirteen patients underwent an open transthoracic esophagectomy with extended en bloc lymphadenectomy combined with laparoscopic gastric tube formation. Clinicopathological data were derived from a prospective database and patient files. Results: The median operation time was 484 min (range 347–573) and the median intraoperative blood loss was 1,500 ml (range 250–3,700). In 2 patients the laparoscopic procedure was converted to a laparotomy because of technical difficulties. Median postoperative stay in the ICU was 3 days (range 1–8) and median hospital stay was 29 days (range 12–104). One patient died in the hospital. Postoperatively 3 patients suffered from anastomotic leakage, 5 from pneumonia and 3 from vocal cord palsy. Conclusions: The complication rate was high in this series of patients undergoing an open extended transthoracic esophagectomy with laparoscopic mobilization of the stomach and gastric tube formation. Laparoscopic mobilization of the stomach and gastric tube formation are feasible, but need carefully guided testing before this technique can be applied routinely.
The Hypothalamic Supraoptic and Paraventricular Nuclei of the Echidna and Platypus
Authors: Ashwell Ken W.S. , Lajevardi Shahab-eddin , Cheng Gang , Paxinos George
Published: July 2006

The monotremes are an intriguing group of mammals that have major differences in their reproductive physiology and lactation from therian mammals. Monotreme young hatch from leathery skinned eggs and are nourished by milk secreted onto areolae rather than through nipples. Parturition and lactation are in part controlled through the paraventricular and supraoptic nuclei of the hypothalamus. We have used Nissl staining, enzyme histochemistry, immunohistochemistry for tyrosine hydroxylase, calbindin, oxytocin, neurophysin and non-phosphorylated neurofilament protein, and carbocyanine dye tracing techniques to examine the supraoptic and paraventricular nuclei and the course of the hypothalamo-neurohypophysial tract in two monotremes: the short-beaked echidna (Tachyglossus aculeatus) and the platypus (Ornithorhynchus anatinus). In both monotremes, the supraoptic nucleus consisted of loosely packed neurons, mainly in the retrochiasmatic position. In the echidna, the paraventricular nucleus was quite small, but had similar chemoarchitectural features to therians. In the platypus, the paraventricular nucleus was larger and appeared to be part of a stream of magnocellular neurons extending from the paraventricular nucleus to the retrochiasmatic supraoptic nucleus. Immunohistochemistry for non-phosphorylated neurofilament protein and carbocyanine dye tracing suggested that hypothalamo-neurohypophysial tract neurons in the echidna lie mainly in the retrochiasmatic supraoptic and lateral hypothalamic regions, but most neurophysin and oxytocin immunoreactive neurons in the echidna were found in the paraventricular, lateral hypothalamus and supraoptic nuclei and most oxytocinergic neurons in the platypus were distributed in a band from the paraventricular nucleus to the retrochiasmatic supraoptic nucleus. The small size of the supraoptic nucleus in the two monotremes might reflect functional aspects of monotreme lactation.
Large Brains and Lengthened Life History Periods in Odontocetes
Authors: Lefebvre Louis , Marino Lori , Sol Daniel , Lemieux-Lefebvre Sébastien , Arshad Saima
Published: July 2006

Due to a decimal place error for body weight of S. longirostris in table 1 we discovered subsequent to the on-line appearance of this paper (Brain Behav Evol 2006;68:218–228), we have had to re-analyze our data. Although the body weight value has now been corrected and is accurately listed in table 1, upon re-analysis with the corrected value we havefound our conclusions to change in a way that does not warrant publication at this time. Therefore, we retract this paper. Louis Lefebvre , Montréal, Canada Lori Marino , Atlanta, Ga., USA Daniel Sol , Barcelona, Spain Sébastien Lemieux-Lefebvre , Montréal, Canada Saima Arshad , Atlanta, Ga., USA
Pilot Phase 2 Trial of 4 Months of Maintenance Pegylated Liposomal Doxorubicin in Patients with Advanced Ovarian Cancer after Complete Response to Platinum and Paclitaxel-Based Chemotherapy
Authors: DiSilvestro Paul A. , Fisher Margaret , Pearl Michael L. , Buhl Ann , Chalas Eva , Valea Fidel A.
Published: July 2006

Background/Aims: Stages III and IV ovarian and peritoneal cancer patients are commonly treated with combination chemotherapy after surgical debulking. This phase II trial investigated the use of pegylated liposomal doxorubicin as consolidation chemotherapy for these patients. Methods: Women with stage III or IV ovarian or primary peritoneal carcinoma demonstrating no clinical evidence of disease after primary therapy were eligible for enrollment. Patients received 4 cycles of 40 mg/m2 IV of pegylated liposomal doxorubicin every 28 days. Results: Twelve patients were enrolled. There were 6 stage IIIC and 6 stage IV patients. Ten patients received 4 cycles. Two patients had dose limiting skin toxicity manifest as hand–foot syndrome and received only 3 cycles. Forty-six of a planned 48 cycles were administered. Median disease-free survival from registration is 10 months with a mean of 18 months. Median overall survival has not yet been reached. Four patients are disease-free, two have relapsed and six have died from disease progression. Conclusion: Pegylated liposomal doxorubicin is a well-tolerated choice for consolidation chemotherapy in patients with ovarian or primary peritoneal carcinoma.
Propionyl-L-Carnitine Therapy: Effects on Endothelin-1 and Homocysteine Levels in Patients with Peripheral Arterial Disease and End-Stage Renal Disease
Authors: Signorelli Salvatore Santo , Fatuzzo Pasquale , Rapisarda Francesco , Neri Sergio , Ferrante Margherita , Oliveri Conti Gea , Fallico Roberto , Di Pino Luigi , Pennisi Giuseppe , Celotta Gabriella , Anzaldi Massimiliano
Published: July 2006

Background/Aims: Recent data have addressed the issue of higher levels of homocysteine (Hcy) and endothelin-1 (ET-1) in end-stage renal disease (ESRD) that may be considered an independent predictor for cardiovascular disease. The prevalence of peripheral arterial disease (PAD) in patients with ESRD has been reported to be relevant, highlighting its clinical importance. We aimed to explore the therapeutic role of propionyl-L-carnitine (PLC) in hemodialysis patients with PAD by measuring ankle/brachial index (ABI), ET-1 and Hcy. Design: Randomized, double-blind, placebo-controlled trial. Methods: Sixty-four patients on hemodialysis with chronic renal insufficiency and PAD were assigned to receive either intravenous PLC (600 mg) or placebo 3 times weekly for 12 months. The ABI and plasma levels of ET-1 and Hcy were measured at baseline, 6 and 12 months. Results: In the PLC-treated group, progressive increases in ABI were observed, while in the placebo group the reverse trend was seen. Highly significant and progressive reductions in plasma levels of ET-1 and Hcy, compared to baseline, were also seen in the PLC-treated group. Conclusions: Hemodynamic flow, endothelial profile and Hcy levels were ameliorated by the administration of PLC in hemodialysis patients with ESRD and PAD.
Reduction in Chronic Allograft Nephropathy by Inhibition of p38 Mitogen-Activated Protein Kinase
Authors: Wada Takashi , Azuma Haruhito , Furuichi Kengo , Sakai Norihiko , Kitagawa Kiyoki , Iwata Yasunori , Matsushima Kouji , Takahara Shiro , Yokoyama Hitoshi , Kaneko Shuichi
Published: July 2006

Background: Chronic allograft nephropathy (CAN) is the major cause for late graft loss and is therefore a key target for therapy. Methods: The impact of p38 mitogen-activated kinase (MAPK) on CAN was investigated by administering FR167653 (32 mg/kg/day), a specific inhibitor of p38 MAPK, for 4 weeks in addition to conventional cyclosporine therapy (1.5 mg/kg/day for 5 days) in an established experimental rat transplantation model. Results: Transplanted rats develop glomerulosclerosis, arterial obliteration, interstitial fibrosis and tubular atrophy, all of which are characteristic of CAN, resulting in shortened survival on 32 weeks. However, the inhibition of p38 MAPK by daily subcutaneous treatment with FR167653 resulted in reduced CAN with preserved renal function and prolonged survival. The FR167653-treated rats had fewer phosphorylated p38 MAPK-positive cells in treated kidneys. Concomitantly, the expression of monocyte chemoattractant protein-1/CCL2 and transforming growth factor-β1 was markedly reduced. Conclusion: These results suggest that p38 MAPK phosphorylation is involved in the pathogenesis of CAN and provide evidence that p38 MAPK is a novel, appealing therapeutic target for combating CAN.
Impairment of Dilator Responses of Cerebral Arterioles During Diabetes Mellitus
Authors: Kitayama Jiro , Faraci Frank M. , Gunnett Carol A. , Heistad Donald D.
Published: June 2006

Background and Purpose—During diabetes, expression of inducible nitric oxide synthase (iNOS) plays an important role in the development of endothelial dysfunction in extracranial blood vessels. Progression of vascular dysfunction after the onset of diabetes differs among vascular beds. In this study, the effects of hyperglycemia/diabetes on vasomotor function were examined in cerebral arterioles at 2 different times in control and iNOS-deficient mice and compared with the effects on carotid arteries.

Methods—Streptozotocin (150 mg/kg IP) was given to induce diabetes. The diameter of cerebral arterioles was measured through a cranial window in diabetic and nondiabetic mice in vivo. Vasomotor function of the carotid artery was examined in vitro.

Results—In diabetic mice, responses of the cerebral arterioles to acetylcholine (1 μmol/L) were normal after 3 weeks of diabetes but were significantly impaired after 5 to 6 weeks of diabetes (4±1% [mean±SEM] increase in diameter) compared with control mice (14±1;P=0.0002). Responses to sodium nitroprusside were similar in diabetic and nondiabetic mice at both time points. In contrast, the vasomotor function of the carotid artery was not affected after 5 to 6 weeks of diabetes. In diabetic iNOS-deficient mice, cerebral arteriolar vasomotor function was not impaired, even after 4 months of diabetes.

Conclusions—During diabetes, endothelial dysfunction of cerebral arterioles requires expression of iNOS and develops earlier than in carotid arteries.
Safety and Effectiveness of Radioactive Coil Embolization of Aneurysms
Authors: Raymond Jean , Mounayer Charbel , Salazkin Igor , Metcalfe Annick , Gevry Guylaine , Janicki Christian , Roorda Sjoerd , Leblanc Philippe
Published: June 2006

Background and Purpose—

Recanalization after coil embolization can be prevented by radiation emitted from
32
P coils. We wanted to determine the upper limits of
32
P activities that could be implanted onto coils with respect to the potential injury to nearby nerves, delay in organization of the clot, and effects on neointima formation and recanalization.

Methods—

We studied the effects of various
32
P activities on recanalization and organization of thrombus after coil occlusion of canine arteries and on neointima formation at the neck of canine carotid bifurcation aneurysms. We also tested potential injury to nerves in the vicinity of radioactive or nonradioactive coils in 3 models: the brachial plexus (near proximal vertebral arteries) and the lingual nerve in a lingual artery bifurcation aneurysm model, both models being treated by radioactive or standard coil occlusion. Finally, we wrapped lingual nerves with nonradioactive or high-activity coils and studied their effects on lingual nerves and tongues. Results were assessed with a pathological scoring system and compared with Mann-Whitney and Kruskal-Wallis tests.

Results—

No deleterious effect of radiation on nerves could be detected. Neointima formation was not hampered, scores of aneurysms treated with
32
P-coils being significantly better when compared with treatments with standard coils (
P
=0.002). Arteries treated with high-activity coils (>3.39 μCi) showed absent recanalization but delayed organization of the clot at 3 months compared with low-activity or nonradioactive coils (
P
<0.05).

Conclusions—

β-Radiation can prevent recanalization after coil occlusion. We could not demonstrate any deleterious effects of radioactivity on nervous structure or on neointima formation. Delayed organization of thrombus provides a rational basis to establish an upper limit for
32
P activities to be implanted onto coils.
Pretreatment With Antiplatelet Agents Is Not Independently Associated With Unfavorable Outcome in Intracerebral Hemorrhage
Authors: Foerch Christian , Sitzer Matthias , Steinmetz Helmuth , Neumann-Haefelin Tobias
Published: June 2006

Background and Purpose—

This study investigated the effect of preexisting antiplatelet therapy on mortality and functional outcome in patients with intracerebral hemorrhage (ICH).

Methods—

Our analysis was based on a large, country-wide stroke registry in Germany. All parameters relevant to this analysis, including age, prehospital status (according to the modified Rankin Scale, mRS), International Classification of Diseases–based diagnosis, and pretreatment with antiplatelet agents or oral anticoagulants, were recorded prospectively. Main outcome measures were in-hospital mortality rate and functional status at hospital discharge (mRS).

Results—

Over a 2-year period, 1691 patients with ICH (ICD-10: I61) were documented (48% female; mean age, 72±12 years). At symptom onset, 26% were taking antiplatelet agents, and 12% were taking oral anticoagulants. By univariate logistic regression, pretreatment with antiplatelet drugs or anticoagulants was found to be a significant predictor of in-hospital mortality (odds ratio [OR], 1.42;
P
=0.008; OR, 1.53;
P
<0.001) and of an unfavorable functional outcome (defined as mRS >2 or death; OR, 1.33,
P
=0.039; OR, 1.51;
P
<0.001). However, after adjustment for age and prehospital status, antiplatelet pretreatment was no longer an independent risk factor of in-hospital death (OR, 1.12;
P
=0.490) or unfavorable functional outcome (OR, 0.97;
P
=0.830), whereas the influence of pretreatment with oral anticoagulants remained significant (OR, 1.45;
P
<0.001; OR, 1.42;
P
=0.009).

Conclusions—

In contrast to oral anticoagulants, pretreatment with antiplatelet agents is not an independent risk factor of mortality and unfavorable outcome in patients with ICH.
Serum C-Reactive Protein Concentration and Genotype in Relation to Ischemic Stroke Subtype
Authors: Ladenvall Claes , Jood Katarina , Blomstrand Christian , Nilsson Staffan , Jern Christina , Ladenvall Per
Published: June 2006

Background and Purpose—

C-reactive protein (CRP) has evolved as an inflammatory risk marker of cardiovascular disease. Several single-nucleotide polymorphisms at the CRP locus have been found to be associated with CRP levels. The aim of the present study was to investigate CRP levels and genetic variants in etiological subtypes of ischemic stroke.

Methods—

The Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) comprises 600 consecutive ischemic stroke cases (18 to 69 years) and 600 matched controls from western Sweden. Stroke subtypes were defined by the TOAST classification. Serum CRP levels were determined by a high-sensitivity immunometric assay.

Results—

CRP levels were significantly higher for all ischemic stroke subtypes compared with controls, both in the acute phase and at the 3-month follow-up. After adjustment for traditional risk factors, CRP at follow-up was related to higher odds ratios (ORs) of overall ischemic stroke (OR, 1.25; 95% CI, 1.09 to 1.43) and large-vessel disease (OR, 1.48; 95% CI, 1.09 to 2.00). The CRP −286C>T>A, 1059G>C, and 1444C>T single-nucleotide polymorphisms showed significant associations with CRP levels. However, neither CRP genotypes nor haplotypes showed an association to overall ischemic stroke.

Conclusions—

This is the first large study on CRP in different TOAST subtypes in a young ischemic stroke population. CRP levels differed between etiological subtypes of ischemic stroke both in the acute phase and at the 3-month follow-up. CRP at follow-up was associated with overall ischemic stroke and the large-vessel disease subtype. Genetic variants at the CRP locus were associated with CRP levels, but no association was detected for overall ischemic stroke.
Assessing School Council Contribution to the Enabling Conditions for Instructional Capacity Building
Authors: Talley Wade Kenneth , Keedy John L.
Published: June 2006

This study identified the enabling conditions related to building instructional capacity created by the councils in three high-performance schools in an urban district. The authors collected the data through observation, interview, and document mining. School-level data were sorted inductively into themes through constant comparative analysis. These school-level data then were analyzed cross-case. Four enabling conditions generalized across the three councils:(a) principal facilitation of decision making through sharing power with council members,(b) schoolwide networking facilitating “bottom-up” problem solving with staff and parents,(c) a focus on student achievement through use of assessment data, and (d) promotion of staff collective accountability for student achievement. The authors extended these findings to those of other studies and discussed why other enabling conditions identified in the literature were not found in this study: financial resources, systematic professional development, program coherence, and “constructive” conflict.
The Unintended Consequences of a Standardized Knowledge Base in Advancing Educational Leadership Preparation
Authors: English Fenwick W.
Published: June 2006

Background: The quest for a “knowledge base” in educational administration resulting in the construction of national standards for preparing school leaders has brought with it an unexpected downside.

Purpose: It is argued that instead of raising the bar for preparing educational leaders, the standards have lowered them, first by embracing only a limited set of the actual responsibilities of school leaders, resulting in programmatic reductionism, and permitting the licensing of school leaders at sites outside the purview of the university, by definition a form of deprofessionalization. The standards also assume the existence of a static knowledge base tied to a static social system. Current skill sets contained in the standards are in their essence antichange and antidemocratic. Conclusions: The major assumption that must be questioned is the notion or requirement of a stable knowledge base that is a political necessity in accreditation and licensing practices but the hallmark of a dead field of studies empirically.
Pharmacokinetics and Safety Profile of Ispronicline (TC‐1734), a New Brain Nicotinic Receptor Partial Agonist, in Young Healthy Male Volunteers
Authors: Dunbar G. , Demazières A. , Monreal A. , Cisterni C. , Metzger D. , Kuchibhatla R. , Luthringer R.
Published: June 2006

Recent research suggests that drugs activating nicotine acetylcholine receptors might be promising therapy in cognitive decline seen in the elderly, including Alzheimer's disease. Ispronicline (TC‐1734), a brain‐selective α4β2 nicotine acetylcholine receptor partial agonist, has shown memory‐enhancing properties in rodents and a good tolerability profile. The safety and the full pharmacokinetic profile of TC‐1734 and its N‐desalkylated metabolite, TC‐1784, were investigated in 2 phase I studies, and results are reported in this article. Study A used a double‐blind, placebo‐controlled, crossover design with a rising single‐dose scheme (2–320 mg). Study B used a double‐blind, placebo‐controlled, parallel‐group design with a rising multiple‐dose scheme (doses: 50, 100, and 200 mg, once daily, × 10 days). Cmax of TC‐1734 was reached around 1 to 2 hours postdose, and mean terminal half‐life (t1/2) ranged from 3 to 5.3 hours (single doses) and from 2.7 to 8.8 hours (repeated doses). No accumulation of TC‐1734 was observed after 10 days. Renal clearance appeared to be a minor method of elimination of TC‐1734 and TC‐1784. A high interindividual variability was noted for all parameters. Across the dose ranges explored, TC‐1734 was safe and well tolerated. No changes of clinical significance were seen on laboratory and cardiovascular parameters. Adverse events were generally of mild to moderate intensity, with dizziness and headache being reported most frequently.