bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic Resonance Investigation of the Upper Spinal Cord in Pure and Complicated Hereditary Spastic Paraparesis
Authors: Sperfeld Anne-Dorte , Baumgartner Annette , Kassubek Jan
Published: February 2006

Neuropathological studies of hereditary spastic paraparesis (HSP) have described axonal loss involving corticospinal and somatosensory tracts in the spinal cord. This MRI-based study was intended to investigate in vivo diameter alterations of the spinal cord in HSP, including both pure HSP (p-HSP, n = 20) and complicated HSP (c-HSP, n = 10). Standard MRI examinations of the cervical and thoracic spinal cord in HSP patients and a control group (n = 54) were analyzed by standardized spinal cord planimetry. In HSP patients, significant atrophy of the upper spinal cord compared to controls was observed at p<0.001 both at the cervical and at the thoracic level. Myelon diameters at both levels were also significantly reduced in the two HSP subgroups in an additional comparison with age-matched subgroups of controls each, but p-HSP and c-HSP groups themselves did not differ. Marked atrophy of the upper spinal cord seems to be associated with HSP, assumedly due to the central-distal axonopathy. However, the differences between p-HSP and c-HSP could not be visualized by structural MRI at spinal cord level.
Changes in Hemodynamics and Acid-Base Balance during Cross-Clamping of the Descending Thoracic Aorta
Authors: Eide T.O. , Aasland J. , Romundstad P. , Stenseth R. , Sæther O.D. , Aadahl P. , Myhre H.O.
Published: February 2006

Aim of the Study: In the clinical situation there is discrepancy between various investigations regarding the cardiac response of thoracic aortic cross-clamping. The aim was therefore to investigate the hemodynamic response and blood gases during proximal aortic cross-clamping (XC) in patients operated for descending thoracic and thoracoabdominal aortic aneurysm without circulatory support. Patients and Methods: Altogether 51 patients operated on for thoracoabdominal (n = 31) or descending thoracic aortic aneurysm (n = 20) were included in the investigation. All patients were operated with aortic XC, but no circulatory support was applied. Hemodynamic variables and blood gases were recorded before and during XC. Results: A significant increase in cardiac output during XC from 4.7 to 6.0 liters/min was observed (p < 0.01). There was a similar percentual increase in heart rate and also the proximal systolic blood pressure increased. A metabolic acidosis occurred during XC. Conclusion: Cardiac output was significantly increased during XC in patients operated on for thoracoabdominal or descending thoracic aneurysm using direct aortic XC without circulatory support. Simultaneously, the heart rate was increased and there was a hyperdynamic circulatory state proximal to the aortic clamp. Redistribution of the blood volume in addition to catecholamine release may be responsible for the observed changes. These observations may influence the selection of operative strategy for some of these patients.
Hyperperfusion Syndrome in Small-for-Size Livers
Authors: Glanemann M. , Eipel C. , Nussler A.K. , Vollmar B. , Neuhaus P.
Published: February 2006

Background: Portal hyperperfusion in small-for-size livers might seriously impair postoperative liver regeneration. Using an experimental model, we investigated splenectomy as a measure to reduce portal blood flow and its impact on postoperative recovery following extended liver resection. Method: Wistar rats underwent partial (90%) hepatectomy with or without splenectomy under temporary inflow occlusion (30 min). In addition to 10-day survival rate, laser Doppler flowmetry of hepatic blood flow and fluorescence microscopic analysis of hepatic microcirculation were performed to assess the effect of splenectomy on initial microvascular reperfusion of liver remnants. Results: While postischemic perfusion failure was comparable between both groups, portal blood flow was significantly reduced after simultaneous splenectomy (3.5 ± 0.4 vs. 5.4 ± 0.4 ml/min). Moreover, red blood cell velocity and volumetric blood flow were reduced in splenectomized animals. These animals experienced lower AST levels (421 ± 36 vs. 574 ± 73 U/l) and a significantly increased survival rate, reaching 6.6 ± 1.3 vs 2.6 ± 0.8 days. Conclusion: Simultaneous splenectomy significantly reduced the risk for postoperative hyperperfusion syndrome in small-for-size livers. Shear-stress-induced liver injury was diminished due to a significant reduction of portal venous blood flow, which positively influenced postoperative regeneration resulting in significantly higher survival.
Glutamine Improves Intestinal Barrier Function in Experimental Biliary Obstruction
Authors: White J.S. , Hoper M. , Parks R.W. , Clements W.D.B. , Diamond T.
Published: February 2006

Objective: To determine the effects of enteral administration of glutamine on intestinal barrier function in experimental biliary obstruction. Background: Extrahepatic biliary obstruction is associated with the failure of intestinal barrier function, allowing bacteria and other substances from the intestine to enter the circulation and initiate a systemic inflammatory response, causing impairment of multiple organs. The amino acid glutamine has been shown to improve intestinal barrier function in other conditions, but its effects in biliary obstruction have not been fully examined. Methods: This study examined the effects of enteral administration of glutamine on intestinal permeability and on bacterial translocation from the intestine in a rodent model of biliary obstruction. Results: Glutamine was shown to reduce intestinal permeability measured as percentage excretion of 14C 7 days after biliary obstruction (0.35 ± 0.03 vs. 0.56 ± 0.085% in controls, p = 0.028), and glutamine administration was also associated with a decreased incidence of bacterial translocation to extra-intestinal sites (p = 0.03). Radiolabelled bacterial studies also demonstrated reduced translocation of bacterial fragments to extra-intestinal sites in glutamine-treated animals (p = 0.01). There was also some evidence of decreased exposure to endotoxin, reduced systemic inflammation and increased bacterial killing by the immune system in glutamine-treated animals. Conclusions: Glutamine modulates intestinal permeability and reduces bacterial translocation in an animal model of experimental biliary obstruction and may increase bacterial killing by the immune system.
Ghrelin and Leptin Elevation in Postoperative Intra-Abdominal Sepsis
Authors: Maruna P. , Gürlich R. , Frasko R. , Rosicka Martina
Published: February 2006

Background: Both ghrelin and leptin are important signals in the regulation of food intake and energy balance. Leptin concentrations are elevated in the majority of obese individuals, and its levels usually correlate with adiposity and body mass index. Ghrelin as a new growth hormone (GH)-releasing peptide was discovered in 1999. Ghrelin stimulates food intake and exhibits gastroprotective properties. Many other regulatory effects of both ghrelin and leptin involving cardiovascular, gastrointestinal, renal, and endocrine systems were revealed. New experimental studies show both hormones as new acute phase reactants in animal models of inflammatory reaction. The aim of this study was to characterize the levels of circulating ghrelin and leptin in relation to systemic inflammatory response. We used a postoperative bacterial sepsis after large abdominal surgery as a model of cytokine network hyperstimulation. Patients and Methods:The prospective study was performed on 25 surgical patients with proven postoperative intra-abdominal sepsis after large abdominal surgery. Plasma levels of ghrelin (RIA), leptin, TNF-α, IL-1β, sIL-2R, IL-6 (ELISA analysis), CRP and α1-antitrypsin (nephelometric analysis) were analyzed. Results: Authors demonstrate statistically significant elevation of plasma ghrelin (492.3 ± 70.6 ng/l) and leptin (31.6 ± 12.2 µg/l) compared with the control group (336.5 ± 46,1, p < 0.01 for ghrelin, 3.5 ± 1.2 µg/l, p < 0.001 for leptin). The regression coefficient was the highest for ghrelin and IL-6 (r = 0,44, p < 0.05), and for ghrelin and TNF (r = 0.43, p < 0.05) in the sepsis group. In regard to leptin, the regression coefficient was the highest for IL-6 and leptin (r = 0.53, p < 0.05) and for leptin and CRP (r = 0.51, p < 0.05). There was no significant correlation between ghrelin and IL-1β, ghrelin and sIL-2R, and leptin and IL-1β. Conclusions: During postoperative intra-abdominal sepsis, both ghrelin and leptin plasma levels are elevated and positively correlate with both inflammatory cytokines (TNF-α, IL-6) and main APP member (CRP). It supports experimental finding that TNF-α and IL-6 can be important regulatory factors of their synthesis. This hormonal reaction is not specific to sepsis – the significant increase of both ghrelin and leptin occurs during an uncomplicated postoperative response, although in a lesser extent than was shown in sepsis.
HMG-CoA Reductase Inhibitors Reduce Matrix Metalloproteinase-9 Activity in Human Varicose Veins
Authors: Nomura S. , Yoshimura K. , Akiyama N. , Mikamo A. , Furutani A. , Aoki H. , Matsuzaki M. , Hamano K.
Published: February 2006

Matrix metalloproteinases (MMPs) have been implicated in tissue degradation in varicose veins. The aim of this study was to investigate the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) on the activity of MMPs in varicose veins. MMP-9 was present at significantly higher levels in varicose veins than in controls and was localized mainly in smooth muscle cells at the tunica media, where marked degradation of the extracellular matrix was observed. Both simvastatin and pravastatin strikingly suppressed MMP-9 activity in ex vivo culture of varicose veins. Simvastatin suppressed MMP-9 at both the mRNA and protein levels as well as at the urokinase-type plasminogen activator protein level, resulting in the dramatic suppression of MMP-9 activity induced by tumor necrosis factor-α. Therefore, statins suppress MMP-9 activity by multiple mechanisms in varicose veins, suggesting they may have clinical potential for the treatment of this disease.
Survival Analysis of Children with Primary Malignant Brain Tumors in England and Wales: A Population-Based Study
Authors: Tseng Jen-Ho , Tseng Ming-Yuan
Published: February 2006

Primary malignant brain tumor is the second most common cancer in children. To investigate factors affecting children’s survival at a population level, data of 3,169 patients (age <15 years) from the Cancer Registry in England and Wales were used. They were diagnosed during 1971–1990 and followed up until 1995. Variables including age, gender, morphology, WHO grade, tumor site, socioeconomic status, geographical region, and period of diagnosis were available for analysis using the Kaplan-Meier method and the Cox hazards ratio (HR) regression. Results showed that the median survival and the 1-, 5-, and 10-year crude survival rate for this population were 8.7 years, 72.4, 54.0, and 49.2% respectively. Survival was influenced by age (HR 0.88/5 years), morphology (ependymoma HR 2.43), WHO grades (HR 1.42/grade), tumor sites (brain stem HR 2.11), and periods of diagnosis (HR 0.88/5 years). Gender, socioeconomic status, and geographical region did not affect their survival. Results from this population-based data are very helpful for comparison with other hospital-based studies and for public health purposes.
Stereotactic Radiation Therapy with Chemotherapy in the Management of Recurrent Medulloblastomas
Authors: Abe Masamitsu , Tokumaru Sunao , Tabuchi Kazuo , Kida Yoshihisa , Takagi Masashi , Imamura Junichi
Published: February 2006

Medulloblastomas are highly lethal tumors when they recur. Very few patients survive with conventional treatment. This report documents the preliminary study results of a treatment for recurrent medulloblastomas consisting of stereotactic radiation therapy (SRT) with chemotherapy. Four patients had local recurrence without apparent metastases and 8 patients had metastases with or without local recurrence. Twelve patients with 18 lesions underwent SRT as a single session (n = 8) or in a hypofractionated manner (n = 10) using a gamma knife or modified linear accelerator. All patients then received systemic chemotherapy. Five patients were treated with one to two sequential courses of high-dose chemotherapy with peripheral blood stem cell transplantation. The reduction in tumor size after SRT was often remarkable. Fourteen of 18 lesions treated disappeared 1–6 months after SRT. Two of 4 patients who had local recurrences without apparent metastasis at the time of SRT are alive without evidence of disease 70 and 72 months after SRT, respectively. In contrast, all 8 patients with metastasis had new lesions either in the spinal canal or on the surface of the brain outside the target area of SRT. Median progression-free survival and overall survival from the time of SRT were 9 and 19 months, respectively. The Kaplan-Meier estimates of PFS and overall survival at 3 years were 17 and 25%, respectively. One patient had brainstem edema after SRT causing bulbar palsy and quadriparesis. One patient died of toxicity of chemotherapy. Our experience suggests that local recurrence can be controlled by SRT with chemotherapy but survival of patients with metastases can not be improved effectively by SRT in conjunction with aggressive chemotherapy.
Central Nervous System Tumors in Patients under Three Years of Age: Treatment Results of a Single Institute
Authors: Varan Ali , Akalan Nejat , Söylemezoğlu Figen , Zorlu Faruk , Yalçın Bilgehan , Akyüz Canan , Kutluk Tezer , Büyükpamukçu Münevver
Published: February 2006

Eighty-six patients under 3 years of age with central nervous system tumors were retrospectively analyzed between 1972 and 2003. Surgical resection was done in all patients except for those with optic glioma, pons glioma and pineal tumor. Three different chemotherapy regimens were used in different time periods. In 48 patients, the tumor was located in the posterior fossa, and 29 patients had a supratentorial tumor. We had 32 (37.2%) patients with embryonic tumors (21 medulloblastoma, 4 ependymoblastoma, 5 with atypical teratoid rhabdoid and 2 with supratentorial primitive neuroectodermal tumors), 21 (24.4%) with ependymoma, 14 (16.3%) with optic glioma, 10 (11.6%) with astrocytoma, 3 (3.5%) with pons glioma and 6 (7.0%) with others. Overall (OS) and event-free survival rates were 49.5 and 40.9%. OS rates according to the tumor localizations were 40.9 and 68.1% in the posterior fossa and supratentorial localizations, respectively (p = 0.001). OS rates were 33.7, 41.3 and 88.8% for the medulloblastoma + primitive neuroectodermal tumor groups, ependymoma and astrocytoma, respectively (p = 0.0001). Most of the patients had primitive embryonic tumors (37.2%). The best prognostic factors were tumor localization and histology.
Infant with Unusually Large Choroid Plexus Papilloma Undergoing Emergency Surgery
Authors: Picht T. , Jansons J. , van Baalen A. , Harder A. , Pietilae T.A.
Published: February 2006

Choroid plexus papillomas are one of the most common tumors of the nervous system in infants. The most frequent early symptoms, megalocephalia and vomiting, caused by elevated intracranial pressure often lead to a diagnosis only at a critical clinical stage. This study describes a case of a 3-month-old infant with a choroid plexus papilloma measuring 7 × 8 × 6 cm originating in the right lateral ventricle. The infant underwent emergency surgery in an acutely deteriorated state, i.e., acute herniation symptoms with fixed and dilated pupils. Despite of the size of the tumor, the proximity to eloquent cortex, and clinically deteriorated state, the infant recovered completely.
Pott’s Puffy Tumor: A Rare Complication of Mastoiditis
Authors: Khan M. Akram
Published: February 2006

Pott’s puffy tumor is rarely seen in the modern era of antibiotics. It is usually seen as intracranial complication following inappropriately treated frontal sinusitis. Up until 2001 there have been only 21 pediatric cases reported in the literature and most have been secondary to frontal sinusitis. Only 1 case has been reported following a latent mastoiditis and that has been in an adult [1]. We report a case in a child who developed Pott’s puffy tumor following mastoiditis.
What Is the Significance of a Significant TDT?
Authors: Ewens Warren J. , Spielman Richard S.
Published: February 2006

This note summarizes the development of the transmission/disequilibrium test (TDT). The initial purpose of the TDT procedure was to test for linkage between a genetic marker and a disease susceptibility locus when an association had been found between the two. An association between disease and marker had sometimes been taken to imply linkage. An association could, however, be due to population stratification even in the absence of linkage. In contrast, the outcome of the TDT is not affected by such stratification. Furthermore, when linkage is not in doubt, the TDT can, in some cases, also provide a test of association between marker and disease. We discuss these various matters in this paper.
Phenotypical Characterisation of the Isolated Norfolk Island Population Focusing on Epidemiological Indicators of Cardiovascular Disease
Authors: Bellis Claire , Hughes Roger M. , Begley Kimberly N. , Quinlan Sharon , Lea Rod A. , Heath Simon C. , Blangero John , Griffiths Lyn R.
Published: February 2006

Objectives: Only 193 people from Pitcairn Island, all descended from 9 ‘Bounty’ mutineers and 12 Tahitian women, moved to the uninhabited Norfolk Island in 1856. Our objective was to assess the population of Norfolk Island, several thousand km off the eastern coast of Australia, as a genetic isolate of potential use for cardiovascular disease (CVD) gene mapping. Methods: A total of 602 participants, approximately two thirds of the island’s present adult population, were characterized for a panel of CVD risk factors. Statistical power and heritability were calculated. Results: Norfolk Islander’s possess an increased prevalence of hypertension, obesity and multiple CVD risk factors when compared to outbred Caucasian populations. 64% of the study participants were descendents of the island’s original founder population. Triglycerides, cholesterol, and blood pressures all had heritabilities above 0.2. Conclusions: The Norfolk Island population is a potentially useful genetic isolate for gene mapping studies aimed at identifying CVD risk factor quantitative trait loci (QTL).
Evidence for Linkage on Chromosome 3q25–27 in a Large Autism Extended Pedigree
Authors: Coon Hilary , Matsunami Nori , Stevens Jeff , Miller Judith , Pingree Carmen , Camp Nicola J. , Thomas Alun , Krasny Lori , Lainhart Janet , Leppert Mark F. , McMahon William
Published: February 2006

Though autism shows strong evidence for genetic etiology, specific genes have not yet been found. We tested for linkage in a candidate region on chromosome 3q25–27 first identified in Finnish autism families [1]. The peak in this previous study was at D3S3037 (183.9 cM). We tested this region in seven affected family members and 24 of their relatives from a single large extended Utah pedigree of Northern European ancestry. A total of 70 single nucleotide polymorphisms (SNPs) were analyzed from 165 to 204 cM. The maximum NPL-all nonparametric score using SimWalk2snp was 3.53 (empirical p val ue = 0.0003) at 185.2 cM (SNP rs1402229), close to the Finnish peak. A secondary analysis using MCLINK supported this result, with a maximum of 3.92 at 184.6 cM (SNP rs1362645). We tested for alterations in a candidate gene in this region, the fragile X autosomal homolog, FXR1. No variants likely to contribute to autism were found in the coding sequence, exon-intron boundaries, or the promoter region of this gene.
Atrophic Remodeling of the Transplanted Rat Heart
Authors: Sharma Saumya , Ying Jun , Razeghi Peter , Stepkowski Stanislaw , Taegtmeyer Heinrich
Published: February 2006

We have previously shown that the common feature of both pressure overload-induced hypertrophy and atrophy is a reactivation of the fetal gene program. Although gene expression profiles and signal transduction pathways in pressure overload hypertrophy have been well studied, little is known about the mechanisms underlying atrophic remodeling of the unloaded heart. Here, we induced atrophic remodeling by heterotopic transplantation of the rat heart. The activity parameters of three signal transduction pathways important in hypertrophy, i.e. mitogen-activated protein (MAP) kinase, mammalian target of rapamycin (mTOR), and Janus kinase/signal transducers and activators of transcription (JAK/STAT), were interrogated. Gene expression of upstream stimuli – insulin-like growth factor 1 (IGF-1) and fibroblast growth factor 2 (FGF-2) – and metabolic correlates, i.e. peroxisome proliferator-activated receptor-α (PPARα) and PPARα-regulated genes, of these pathways were also measured. In addition, we measured transcript levels of genes known to regulate skeletal muscle atrophy, all of which are negatively regulated by IGF-1 (Mafbx/Atrogin-1, MuRF-1). Atrophic remodeling of the heart was associated with increased expression of IGF-1 and FGF-2. Transcript levels of the nuclear receptor PPARα were decreased, as were the levels of PPARα-regulated genes. Furthermore, there was phosphorylation of ERK1, STAT3, and p70S6K with unloading. Consistent with the increase in IGF-1, we found a decrease in Mafbx/Atrogin-1 and MuRF-1 transcript levels. Rapamycin administration at 0.8 mg/kg/day for 7 days resulted in enhanced atrophy and attenuated the phosphorylation of ERK1, STAT3, and p70S6K without altering gene expression. We conclude that there is significant crosstalk between the mTOR, MAP kinase, and JAK/STAT signaling cascades. Furthermore, ubiquitin ligases, known to be essential for skeletal muscle atrophy, decrease in unloading-induced cardiac atrophy.
Aggressiveness, Anger and Eating Disorders: A Review
Authors: Truglia Elisabetta , Mannucci Edoardo , Lassi Stefano , Rotella Carlo Maria , Faravelli Carlo , Ricca Valdo
Published: February 2006

Anger and aggressive behaviours, especially those self-directed, are frequent in subjects suffering from anorexia nervosa and bulimia nervosa. They increase the complexity of the clinical features, change the prognosis and cause a more difficult management of these disorders. In order to elucidate the complex relationships between eating disorders, anger and aggressiveness, the history of traumatic experiences, the prevalence of dissociative, obsessive, impulsive and compulsive symptoms, as well as the role of severe personality disorders in subjects suffering from anorexia nervosa, bulimia nervosa and self-injurious behaviours are considered. In the final section of this paper, a model exploring such a relationship in the light of the undefined sense of self is described.
Circadian Cholinergic Rhythms: Implications for Cholinesterase Inhibitor Therapy
Authors: Davis Bonnie , Sadik Kay
Published: February 2006

Therapies for Alzheimer’s disease (AD) at present augment the deteriorating cholinergic system, are reasonably well tolerated, and are convenient, given once or twice a day. They may, however, support or oppose endogenous circadian cholinergic rhythms. Drugs with a duration of action longer than a day are at odds with the physiology of the cholinergic system, which is active during the day and quiescent at night. Sleep and the consolidation of daytime experience into memory may be disturbed. Tolerance commonly develops, substantial counterregulatory increases in acetylcholinesterase (AChE) have been measured, and brain AChE inhibition is lower than predicted. Therefore, the duration of action and timing of administration, as they relate to natural cholinergic rhythms, are factors to be considered in optimizing cholinergic AD therapeutics.
CSF Biomarkers for Alzheimer’s Disease: Levels of β-Amyloid, Tau, Phosphorylated Tau Relate to Clinical Symptoms and Survival
Authors: Wallin Å.K. , Blennow K. , Andreasen N. , Minthon L.
Published: February 2006

Cerebrospinal fluid (CSF) samples from 21 patients with a clinical diagnosis of Alzheimer’s disease (AD) participating in a 5-year treatment study with the choline esterase inhibitor tacrin were retrospectively analyzed for the contents of β-amyloid (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau). A significant positive correlation between the level of P-tau and the number of symptoms according to the DSM-IV criteria (p = 0.041) and the NINCDS-ADRDA (p = 0.029) was observed (i.e. higher levels were found in cases with more symptoms). A significant positive correlation between T-tau, P-tau and ADAS-cog score was identified (i.e. higher levels were found with more severe cognitive dysfunction). Patients who died during the 5-year follow-up had significantly lower levels of Aβ42 (p = 0.011) than those who were still alive. Patients who had died in a 6-year follow-up had significantly lower levels of Aβ42 (p = 0.034) and higher levels of T-tau (p = 0.041) than patients still alive. Conclusion: CSF biomarkers do aid the clinical diagnosis of AD. Increased levels of P-tau and T-tau are possible markers for severity and abundance of symptoms in AD. Low levels of Aβ42 may indicate a higher risk of early death in AD.
Decrease in NADPH-Cytochrome P450 Reductase Activity of the Human Heart, Liver and Lungs in the Presence of Alpha-Lipoic Acid
Authors: Dudka Jaroslaw
Published: February 2006

Background: NADPH-cytochrome P450 reductase (CPR) is the electron donor protein for several oxygenase enzymes located in the endoplasmic reticulum. These oxygenases include P450 family enzymes involved in the metabolism of endogenous and exogenous substances. The enzyme is involved in adriamycin (anticancer drug) and paraquat (herbicide) toxicity. CPR is a flavoprotein containing both flavine-adenine dinucleotide and flavine mononucleotide. A structural study showed the presence of several sulfhydryl (SH) groups in the CPR molecule. Some of them play a key role in catalytic activity. As α-lipoic acid contains a disulfide bond, it may react with the SH group of CPR. The aim of the study was to evaluate the effect of α-lipoic acid on human P450 reductase activity. Methods: The activity of the enzyme was determined by measuring the rate of cytochrome c reduction at 550 nm, in vitro, using heart, liver and lung microsomes. Results: The activity of CPR was decreased in all organs after addition of α-lipoic acid to the reaction mixture at concentrations of 0.01, 0.10 and 1.00 mM. The decreases in CPR activity were concentration-dependent and the sequence of relative inhibition was as follows: heart >lung >liver. However, the statistical significance of CPR activity vs. control was observed in the heart in the presence of 1.00 mM α-lipoic acid and in the lung at 0.10 and 1.00 mM α-lipoic acid. Conclusion: α-Lipoic acid decreased NADPH-CPR activity in the lung and heart. The present results are promising for future studies to obtain the most effective antidote for adriamycin and paraquat toxicity.
Methionine-Induced Elevation of Plasma Homocysteine Concentration Is Associated with an Increase of Plasma Cholesterol in Adult Rats
Authors: Hirche Frank , Schröder Arlette , Knoth Berit , Stangl Gabriele I. , Eder Klaus
Published: February 2006

Background and Aims: Dietary methionine affects cholesterol metabolism in growing rats. Methionine effects on adult rats and mechanisms by which methionine alters the lipid metabolism are not fully elucidated. We investigated possible mechanisms by which dietary methionine acts on lipid metabolism of adult rats. Methods: Male adult rats were divided into three groups (n = 10) and were fed casein-based diets differing in methionine concentration (low-methionine diet: 0.96 g/kg; adequate-methionine diet: 2.22 g/kg, high-methionine diet: 6.82 g/kg) for 4 weeks. Concentrations of triacylglycerols and cholesterol in plasma and lipoproteins, concentration of homocysteine in plasma, concentration of cholesterol in liver, fecal lipid excretion, expression of hepatic HMG-CoA reductase, phosphatidylethanolamine N-methyltransferase 2 (PEMT-2) and of LDL receptor were measured. Results: Rats fed the high-methionine diet had higher plasma homocysteine concentrations than rats fed the low-methionine diet (p < 0.05). Although concentrations of cholesterol in plasma and lipoproteins were not different between the groups, there was a distinct positive correlation between circulating plasma homocysteine and plasma cholesterol (R2 = 0.55, p < 0.001). The fecal excretion of cholesterol and bile acids was not altered by dietary methionine. The relative mRNA concentration of HMG-CoA reductase and of LDL receptor remained unaffected by dietary methionine. Gene expression of PEMT-2 was higher in rats fed the high-methionine diet than in rats fed the other diets (p < 0.05). Conclusion: The results demonstrate that dietary methionine contributes to a rise in circulating homocysteine concentration which positively correlates with the concentration of plasma cholesterol. However, the effects of methionine on cholesterol metabolism of adult rats were relatively weak.
Is Helicobacter pylori a Pathogenic Agent of the Cervix Uteri?
Authors: Yildirim Basak , Acikbas İbrahim , Şengül Mustafa , Akbulut Metin , Kaleli Ilknue , Bagci Huseyin
Published: February 2006

Background:Helicobacter pylori is a gram-negative, microaerophilic rod-shaped bacterium that lives beneath the gastric mucosal layers, on the surface of epithelial cells. Gastric infection with this organism causes inflammation of the gastric mucosa, which can lead to gastritis, duodenal or gastric ulcers and even in rare cases to gastric carcinoma or MALT lymphoma. Approximately 50% of the population of the entire world is believed to be infected with H. pylori, but the exact route of transmission is still uncertain. It has been speculated that the cervix, with its endocervical columnar epithelium and acidic mucous layer, might provide a suitable environment for H. pylori. H. pylori might be a pathogenic agent for cervical infection. In order to address this issue we studied H. pylori in the endocervical tissue. Methods: To investigate our hypothesis, we examined cervical tissue using PCR, culture, and Gramstain. Thirty-three cervices from women who underwent total hysterectomy for noninvasive noncervical benign uterine diseases were analyzed in this study. Twenty-one patients had cervicitis and 12 patients were included as controls. Results: Of the 29 patients studied, none showed evidence of H. pylori infection. H. pylori was not detected by PCR, histology, or culture. Conclusions: We could not detect H. pylori in the cervix of patients with cervicitis. H. pylori-infected patients’ cervices remain to be investigated, and a larger study is needed to draw firm conclusions.
Reduction in Plasma Glucose after Lipid Changes in Mice Fed Fish Oil, Docosahexaenoic Acid, and Eicosapentaenoic Acid Diets
Authors: Higuchi Tomoyuki , Shirai Nobuya , Suzuki Hiramitsu
Published: February 2006

Background/Aim: Effects of the dietary docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and fish oil on weekly changes in plasma glucose, total cholesterol, triacylglycerol, and phospholipid concentrations of male Crlj:CD-1 mice were investigated. Method: Animals were fed five different experimental diets which contained 6.0% lard (lard diet), 6.0% fish oil (fish oil diet), 1.5% DHA-ethyl ester + 4.5% lard (DHA diet), 0.4% EPA-ethyl ester + 5.6% lard (EPA diet), and 1.5% DHA-ethyl ester + 0.4% EPA ethyl ester + 4.1% lard (DHA+EPA diet) for 17 weeks. Glucose and lipid concentrations in plasma collected at weeks 0, 1, 2, 4, 6, 8, 12, and 16 were measured. Results: Plasma phospholipid concentrations were significantly lower in mice fed the fish oil and DHA+EPA diets than in those fed the lard diet at week 2. Plasma total cholesterol and glucose concentrations were significantly lower in the fish oil diet group than in the lard diet group at weeks 6 and 8, respectively. Conclusion: These results indicate that the decreases in plasma glucose concentrations in response to intakes of DHA and EPA in mice take place over a longer period of time than similar decreases in the plasma lipid concentrations.
Effect of Berberine on Interleukin 8 and Monocyte Chemotactic Protein 1 Expression in a Human Retinal Pigment Epithelial Cell Line
Authors: Cui Hu-Shan , Hayasaka Seiji , Zhang Xue-Yun , Hayasaka Yoriko , Chi Zai-Long , Zheng Lian-Shun
Published: February 2006

Purpose: The aims of this study were to examine the effects of berberine, an alkaloid isolated from some medicinal herbs, on interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) expression in a human retinal pigment epithelial cell line (ARPE-19) stimulated with interleukin 1β (IL-1β) or tumor necrosis factor α (TNF-α). Methods: ARPE-19 cells were cultured to confluence. Berberine and IL-1β or TNF-α were added to the medium. IL-8 mRNA and MCP-1 mRNA were measured by semiquantitative reverse-transcription polymerase chain reaction and real-time polymerase chain reaction. IL-8 and MCP-1 protein concentrations in the media were measured using enzyme-linked immunosorbent assay. Results: Berberine dose-dependently inhibited IL-8 mRNA and MCP-1 mRNA expression of the cells and protein levels in the media stimulated with IL-1β or TNF-α. Conclusion: These findings indicate that berberine dose-dependently inhibited the expression of IL-8 and MCP-1 induced by IL-1β or TNF-α.
The Brain-Derived Neurotrophic Factor Gene as a Possible Susceptibility Candidate for Alzheimer’s Disease in a Chinese Population
Authors: Tsai Shih-Jen , Hong Chen-Jee , Liu Hsiu-Chih , Liu Tsung-Yun , Liou Ying-Jay
Published: February 2006

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may represent a candidate gene conferring susceptibility to Alzheimer’s disease (AD). This is because it has an important role in neuronal survival, and a decreased central level of BDNF is observed in AD. Some previous studies, though not all, have demonstrated that BDNF C270T polymorphisms might be associated with AD susceptibility. We examined the association of the C270T polymorphisms with sporadic AD in a Chinese cohort of 175 AD patients and 189 controls. We also tested BDNF Val66Met-C270T haplotypes for an interaction with the apolipoprotein E υ4 (APOE4) allele in AD. The results showed that the frequency of the 66Val allele was significantly lower in AD than controls (p = 0.031), but no significant difference in C270T allele or genotype frequencies was observed between AD cases and controls. Global case-control haplotype analysis showed that there is significant difference in haplotype distribution between both groups (p = 0.033). Stratification of the data according to the APOE status showed that in APOE4 allele bearers there was no significant difference in the frequency of haplotype 66Val-270C between AD and controls (p = 0.125), although there was a significant difference between the two groups in non-APOE4 carriers (p = 0.002). These results suggest that BDNF genetic variation may possibly affect the risk for AD, particularly in subjects who are negative for APOE4.
Neuropathologic Correlates of Apathy in Alzheimer’s Disease
Authors: Marshall Gad A. , Fairbanks Lynn A. , Tekin Sibel , Vinters Harry V. , Cummings Jeffrey L.
Published: February 2006

Apathy is the most commonly observed behavioral disturbance in Alzheimer’s disease (AD) and has been suggested to be frontally mediated. Neuritic plaque (NP) and neurofibrillary tangle (NFT) counts were performed for 8 brain regions in 29 subjects with definite AD. Neuropsychiatric Inventory (NPI) for autopsied subjects was obtained from questioning of caregivers of subjects included in the study. Chronic apathy and total NPI composite scores correlated with anterior cingulate NFT counts (r = 0.518, p = 0.01, and r = 0.438, p = 0.032). This analysis suggests that chronic apathy in AD correlates with a greater anterior cingulate NFT burden and that chronic behavioral changes are more reflective than acute changes of disease pathology.
Etiology of Balkan Endemic Nephropathy and Associated Urothelial Cancer
Authors: Stefanovic Vladisav , Toncheva Draga , Atanasova Srebrena , Polenakovic Momir
Published: February 2006

Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression to terminal renal failure. Evidence has accumulated that BEN is an environmentally induced disease. There are three actual theories attempting to explain the environmental cause of this disease: (1) the aristolochic acid hypothesis, which considers that the disease is produced by chronic intoxication with Aristolochia, (2) the mycotoxin hypothesis, which considers that BEN is produced by ochratoxin A, and (3) the Pliocene lignite hypothesis, which proposes that the disease is caused by long-term exposure to polycyclic aromatic hydrocarbons and other toxic organic compounds leaching into the well drinking water from low-rank coals in the vicinity to the endemic settlements. Moreover, it was suggested that BEN risk is influenced by inherited susceptibility. Therefore, it has been expected that molecular biological investigations will discover genetic markers of BEN and associated urothelial cancer, permitting early identification of susceptible individuals who may be at risk of exposure to the environmental agents. Since kidney pathophysiology is complex, gene expression analysis and highly throughput proteomic technology can identify candidate genes, proteins and molecule networks that eventually could play a role in BEN development. Investigation of gene-gene and gene-environment interactions could be the content of further studies determining the precise risk for BEN.
Effect of Corticosteroids or Diuretics in Low-Tone Sensorineural Hearing Loss
Authors: Suzuki Mitsuya , Otake Rika , Kashio Akinori
Published: February 2006

Objectives: We retrospectively analyzed 225 patients with acute low-tone sensorineural hearing loss (ALSHL), comparing the effectiveness of corticosteroid and diuretic therapy, and also determining the factors affecting hearing recovery. Design: Retrospective clinical record review. Methods: Multivariate logistic regression analysis. Results: Analyses identified unfavorable factors such as aging, late initiation of treatment, and pretreatment pure-tone hearing thresholds at three lower frequencies adding up to 95 dB and more. Multivariate logistic regression analysis indicated a significantly greater improvement in hearing in patients treated with corticosteroids at high initial and total doses than in those treated with vitamin B12 and ATP without adding corticosteroids. In 145 patients treated with corticosteroids, multivariate logistic regression analysis showed a trend toward greater improvement with high initial and total doses than with low doses. Conclusion: Corticosteroids should be changed from low to high doses within 7 days after onset of ALSHL, if low doses are failing.
Evaluation of Inspiratory Muscle Function in a Healthy Austrian Population – Practical Aspects
Authors: Reiter M. , Totzauer A. , Werner I. , Koessler W. , Zwick H. , Wanke T.
Published: February 2006

Background: There is no clear evidence whether inspiratory muscle strength (Pimax) is closely linked to inspiratory muscle endurance (Tlim). Moreover, normal values of Tlim, measured by flow-resistive loads, have not been established. Objectives: We tried to find answers to the following questions: Is it possible to establish normative values of Tlim when using flow-dependent, resistive loads? Are Pimax and Borg scale values predictors of Tlim? Are anthropometric and spirometric data closely related to Tlim? Is it really necessary to measure Tlim in addition to Pimax when evaluating inspiratory muscle function? Methods: Sixty-eight healthy Austrian volunteers between 17 and 75 years of age and with a sedentary lifestyle participated in our study. Pimax was defined as the maximal inspiratory mouth pressure, measured with a differential pressure transducer. Tlim was determined as the time span until exhaustion, while breathing against a resistive loading device. Results: Pimax values showed a low intra- and high interindividual variability for both sexes and were significantly age, weight and height dependent. For male subjects, Pimax was also significantly related to spirometric parameters. Tlim values showed a very high interindividual variability, but a low intraindividual variability. Interestingly, no correlation was found between Tlim and Pimax, nor lung function parameters and age. Conclusions: The results indicate that both Pimax and Tlim have to be determined when inspiratory muscle function is measured. Normal values for Tlim, evaluated by flow-resistive loads, cannot be satisfactorily established due to the high interindividual variability.
β2-Adrenoceptor Genotype and Function Affect Hemodynamic Profile Heterogeneity in Postural Tachycardia Syndrome
Authors: Jacob Giris , Garland Emily M. , Costa Fernando , Stein C. Michael , Xie Hong-Guang , Robertson Rose Marie , Biaggioni Italo , Robertson David
Published: February 2006

Previous studies suggest that the β2-adrenoceptor functions abnormally in patients with postural tachycardia syndrome (POTS) and may contribute to their altered hemodynamic profile. To test the hypothesis that the β2-adrenoceptor response is decreased in POTS, we studied: (1) the arterial vasodilation response to the β agonist, isoproterenol, and (2) the distribution of common polymorphisms (codons 16 and 27) of the gene coding the receptor (β
2
-AR) in a large population with POTS. We measured plasma catecholamines and monitored hemodynamics and changes in forearm and leg blood flow to incremental doses of intraarterial isoproterenol in 9 patients with POTS compared with 8 healthy subjects. For polymorphism assessment we collected DNA from 57 patients with POTS and compared with 67 age-sex matched healthy subjects. Circulating catecholamines were significantly higher in POTS subjects compared with controls. Intrabrachial and intrafemoral isoproterenol infusion elicited a dose-dependent increase in blood flow. In healthy subjects, blood flow increased (mean±SEM) 400±70% in the forearm and 170±40% in the leg, but only 280±60% in forearms and 120±20% in legs of patients with POTS (ANOVA for both P<0.001). The genotype and allele distributions for codons 16 and 27 β
2
-AR variants were not different in the 2 groups. However, the blood pressure and plasma norepinephrine levels diverged in patients according to their genotype. Patients with
Gly16Gly
and patients with
Glu27Glu
had lower plasma catecholamines and higher supine and upright blood pressure, compared with other genotypes. Therefore, both decreased β2-adrenoceptor-related vasodilation and β
2
-AR polymorphisms may contribute to the hemodynamic diversity of patients with POTS.
Changing Incidence and Survival for Heart Failure in a Well-Defined Older Population, 1970–1974 and 1990–1994
Authors: Barker William H. , Mullooly John P. , Getchell William
Published: February 2006

Background—

An epidemic increase in heart failure (HF) mortality, hospitalization, and prevalence rates has been observed among older persons in recent years. It is unclear whether this reflects an increase in incidence or survival.

Methods and Results—

We conducted a retrospective cohort study comparing HF in 1970 to 1974 and 1990 to 1994 among persons ≥65 years old belonging to a large, well-defined population with complete medical records available for research. Using Framingham clinical criteria, we identified incident cases of HF in the respective periods. Age-specific and age-adjusted incidence, mortality, and survival rates were compared. Cox proportional-hazards models were used to assess association of comorbidities and medications with survival. During 38 800 and 127 419 person-years for 1970 to 1974 and 1990 to 1994, respectively, 387 and 1555 confirmed incident cases were identified. When adjusted for age, incidence increased by 14% (95% CI 2% to 28%). Increased incidence tended to be greater for older persons and for men. Based on 5-year follow-up and adjustment for age and comorbidities, the mortality hazards decreased 33% (95% CI 14% to 48%) among men and 24% (95% CI −1% to 43%) among women.

Conclusions—

The epidemic increase in HF among the older population between the 1970s and 1990s is associated with increased incidence and improved survival, with both of these effects being greater in men.
Characterization of Acute and Chronic Myocardial Infarcts by Multidetector Computed Tomography
Authors: Gerber Bernhard L. , Belge Bénédicte , Legros Gabin J. , Lim Pascal , Poncelet Alain , Pasquet Agnès , Gisellu Giovanna , Coche Emmanuel , Vanoverschelde Jean-Louis J.
Published: February 2006

Background—

We evaluated whether contrast-enhanced multidetector computed tomography (CE-MDCT) might characterize myocardial infarct (MI) with patterns similar to those obtained by contrast-enhanced magnetic resonance (CE-MR) and studied the underlying mechanisms.

Methods and Results—

In vivo infarct characterization by CE-MDCT was shown to be feasible between 4 and 20 minutes after contrast injection in 7 pigs with MI. Subsequently, in 16 patients with acute MI and 21 patients with chronic MI, contrast patterns by CE-MDCT were related to CE-MR. Eighteen patients had hypoenhanced regions on early CE-MDCT images at the time of coronary imaging, and 34 patients had hyperenhanced regions on images acquired 10 minutes later. On a segmental basis, there was moderately good concordance of early hypoenhanced regions (92%, κ=0.54,
P
<0.001) and late hyperenhanced regions (82%, κ=0.61,
P
<0.001) between CE-MDCT and CE-MR. Absolute sizes of early hypoenhanced (6±16 versus 7±16 g,
P
=0.25) and late hyperenhanced (36±34 versus 31±40 g,
P
=0.14) regions were similar on CE-MDCT and CE-MR and were highly correlated (
r
=0.93,
P
<0.001 and
r
=0.89,
P
<0.001 respectively). In 8 retrogradely perfused infarcted rabbit hearts, contrast kinetics of iomeprol were similar to gadodiamide, ie, slow wash in (8.7±6.7 versus 1.2±0.3 minutes,
P
<0.001) in infarct core and slow washout (20±12 versus 2.5±0.5 minutes,
P
<0.001) in both infarct core and rim compared with the remote region.

Conclusions—

Because iodated contrast agents have similar kinetics in infarcted and noninfarcted myocardium as gadolinium DPTA, CE-MDCT can characterize acute and chronic MI with contrast patterns similar to CE-MR. CE-MDCT may thus provide important information on infarct size and viability at the time of noninvasive coronary imaging.