bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of angiotensin‐converting enzyme inhibition on functional class in patients with left ventricular systolic dysfunction—a meta‐analysis
Authors: Abdulla Jawdat , Pogue Janice , Abildstrøm Steen Z. , Køber Lars , Christensen Erik , Pfeffer Marc A. , Yusuf Salim , Torp‐Pedersen Christian 
Published: July 2005

AbstractBackground:The effect of angiotensin converting enzyme (ACE) inhibitors on symptoms in patients with left ventricular systolic dysfunction (LVSD) is controversial.Aims:To perform a meta‐analysis of studies evaluating effect of ACE inhibitors on New York Heart Association (NYHA) class in patients with LVSD.Methods:Individual data from 10389 patients in NYHA classes I–IV from four large long‐term studies (2–4‐year follow‐up) and summary data from 2302 patients in NYHA classes II–IV from 16 short‐term studies (3 months follow‐up) were meta‐analysed to assess changes in NYHA class.Results:The large long‐term studies showed a significant improvement in the worst NYHA classes (classes II–IV compared to class I) in the ACE inhibitor arm versus placebo, odds ratio (OR)=0.875 (0.811–0.943) p=0.0005. This effect was only present in studies which included patients with chronic heart failure and was particularly pronounced on deterioration to the worst NYHA class IV, OR=0.66 (0.52–0.84) p=0.001. There was no effect in the studies which included patients after myocardial infarction. The short‐term chronic heart failure studies showed a significant improvement in NYHA class; OR for improvement of at least one NYHA class was 2.11 (1.48–2.98, 95% CI) p<0.0001.Conclusion:ACE inhibition significantly improves symptomatic status measured as NYHA classification in patients with chronic heart failure.
Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure
Authors: Tousoulis Dimitris , Antoniades Charalambos , Vassiliadou Carmen , Toutouza Marina , Pitsavos Christos , Tentolouris Costas , Trikas Athanasios , Stefanadis Christodoulos 
Published: July 2005

AbstractBackground:Heart failure has been associated with impaired endothelial function, increased inflammatory process and elevated oxidative stress status. Both statins and vitamin E separately improve endothelial function in patients with hypercholesterolemia and/or advanced atherosclerosis.Aim:To evaluate the effect of atorvastatin alone or in combination with vitamin E on endothelial function and serum levels of interleukin‐6 (IL‐6), tumor necrosis factor alpha (TNF‐α) and vascular cells adhesion molecule (sVCAM‐1) in patients with ischemic heart failure.Methods:Thirty‐eight male patients with ischemic cardiomyopathy were randomly divided into three groups and received either atorvastatin 10 mg/day (n=14), a combination of atorvastatin 10 mg/day plus vitamin E 400 IU/day (n=12), or no statin or antioxidant treatment (n=12), controls) for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain‐gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was defined as the percent change of FBF from rest to the maximum flow during reactive hyperemia or after nitrate administration, respectively.Results:RH% was significantly improved in both the atorvastatin‐treated (p<0.01) and atorvastatin plus vitamin E groups (p<0.05), but the increase was significantly higher in the atorvastatin‐treated group (p<0.05). Serum levels of IL‐6, TNF‐α and sVCAM‐1 were decreased in the atorvastatin‐treated group (p<0.05 for all), but remained unaffected in the other two groups (p=NS for all).Conclusions:Low dose atorvastatin treatment improves endothelial function and reduces the expression of proinflammatory cytokines and adhesion molecules in patients with ischemic heart failure, an effect partly depressed by vitamin E.
Clinical trials update from the European Society of Cardiology Heart Failure meeting and the American College of Cardiology: Darbepoetin alfa study, ECHOS, and ASCOT‐BPLA
Authors: Cleland John G.F. , Coletta Alison P. , Clark Andrew L. , Velavan Periaswamy , Ingle Lee 
Published: July 2005

AbstractThis article provides information and a commentary on landmark trials presented at the European Society of Cardiology Heart Failure meeting held in June 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. The erythropoiesis stimulating protein, darbepoetin alfa, increased haemoglobin levels, improved quality of life and showed a trend for improved exercise duration in anaemic patients with symptomatic chronic heart failure. In the ECHOS study, the selective dopamine agonist nolomirole (CHF1035) showed no benefit in heart failure patients. Preliminary results of the ASCOT‐BPLA study, which were reported at the American College of Cardiology meeting in March 2005, showed that in hypertensive patients, treatment with a calcium antagonist plus an ACE inhibitor was more effective at reducing cardiovascular outcomes than atenolol plus a diuretic.
Reliability and validity of a modified Brief Pain Inventory short form in patients with osteoarthritis
Authors: Mendoza Tito , Mayne Tracy , Rublee Dale , Cleeland Charles 
Published: July 2005

AbstractThe Brief Pain Inventory short form (BPI‐sf) is a validated, widely used, self‐administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions. A modified version was used daily in randomised control trials of patients with arthritis undergoing treatment with cyclooxygenase‐2 specific inhibitors and non‐steroidal anti‐inflammatory drugs. Results indicate that the modified BPI‐sf, much like the original scale, was internally reliable, consistent over time, and had good construct, as well as convergent and predictive validity in assessment of patients suffering from conditions of chronic pain. Each scale and individual pain intensity item refers to changes in osteoarthritis pain associated with medication use. The modified BPI‐sf, like the parent scale, is a valid and reliable tool for situations in which pain is assessed daily and minimises the burden placed on patients to record information necessary for scientific investigations.
Medical vs. surgical evacuation of first‐trimester spontaneous abortion
Authors: Moodliar S. , Bagratee J.S. , Moodley J. 
Published: July 2005

AbstractObjective: To determine whether management of incomplete first‐trimester abortion with vaginal misoprostol in an under‐resourced setting is a viable treatment option. Methods: A total of 94 women were randomized to 600 μg of misoprostol intravaginally or to surgical curettage. The women receiving misoprostol were administered a second dose if the abortion was incomplete; and if still not complete after a week, evacuation of retained products of conception was performed. All women had a follow‐up visit 2 weeks following complete abortion. Results: The overall success rate of medical management was 91.5%, with 15 of 47 successful cases after 1 dose of misoprostol; 8.5% of the 47 women required evacuation of retained products of conception after 1 week because of treatment failure. The success rate in the surgical arm was 100%. Patients in the medical arm had a longer duration of bleeding and a greater need for analgesia. There were no differences in hemoglobin levels, white blood cell count, adverse effects, pain score, and satisfaction with treatment at the follow‐up visit. However, more women who received the medical treatment would recommend it or choose it in the future. Conclusion: Medical management using 600 μg of misoprostol in 2 doses is effective to treat incomplete first‐trimester abortions in an under‐resourced setting when there is no evidence of uterine sepsis.
A direct interview family study of obsessive–compulsive disorder. II. Contribution of proband informant information
Authors: LIPSITZ JOSHUA D. , MANNUZZA SALVATORE , CHAPMAN TIMOTHY F , FOA EDNA B. , FRANKLIN MARTIN E. , GOODWIN RENEE D. , FYER ABBY J. 
Published: July 2005

Background. Overall findings of our first direct interview family study of obsessive–compulsive disorder (OCD) indicated that OCD is familial. In this replication study, we carefully examined the role of informant data in ascertaining OCD in relatives.Method. We interviewed 112 relatives of 57 OCD patients and 115 relatives of 41 not ill controls predominantly by telephone. Additional analyses included a combined sample of relatives about whom any diagnostic information was available (228 OCD and 239 controls). To examine the contribution of proband information about relatives, we considered two sets of best-estimate diagnoses. First, we ascertained best-estimate diagnoses for relatives using information from direct interviews and from all informants except the proband. Then, we re-diagnosed relatives based on all available information, including reports from the proband about their relatives.Results. When relative diagnoses were derived without the benefit of proband informant reports, no evidence of familial OCD transmission was found. When diagnoses were made including information from the proband about the relative, evidence of familial OCD was found, but only when the diagnostic threshold was lowered to include cases with probable OCD or OCD symptoms. Other diagnoses (generalized anxiety disorder, social phobia, drug use disorder) were also higher among OCD relatives.Conclusions. This second study provides less robust support for familial transmission of OCD. Evidence for familial transmission of OCD was found only when diagnoses were made using information from the affected proband about their relatives. Taken in context of past findings, our own inconsistent results suggest that OCD may be heterogeneous with regard to familial transmission. Also, more careful attention should be paid to the contribution of informant reports, especially from relatives affected by the same disorder.
Normal levels of prepulse inhibition in the euthymic phase of bipolar disorder
Authors: BARRETT SUZANNE LUCIA , KELLY CHRISTOPHER , WATSON DAVID ROBERT , BELL ROBERT , KING DAVID JOHN 
Published: July 2005

Background. Deficits in prepulse inhibition (PPI) of the acoustic startle response have been suggested as a potentially useful endophenotype for schizophrenia spectrum disorders and may explain certain symptoms and cognitive deficits observed in the psychoses. PPI deficits have also been found in mania, but it remains to be confirmed whether this dysfunction is present in the euthymic phase of bipolar disorder.Method. Twenty-three adult patients with DSM-IV bipolar disorder were compared to 20 controls on tests of acoustic startle reactivity and PPI of the startle response. Sociodemographic and treatment variables were recorded and symptom scores assessed using the Hamilton Depression Inventory and the Young Mania Rating Scale.Results. Overall, the patient and control groups demonstrated similar levels of startle reactivity and PPI, although there was a trend for the inter-stimulus interval to differentially affect levels of PPI in the two groups.Conclusions. In contrast to bipolar patients experiencing a manic episode, general levels of PPI were normal in this euthymic sample. Further studies are required to confirm this finding and to determine the mechanisms by which this potential disruption/normalization occurs. It is suggested that an examination of PPI in a high-risk group is required to fully discount dysfunctional PPI as a potentially useful endophenotype for bipolar disorder.
Saccadic distractibility is elevated in schizophrenia patients, but not in their unaffected relatives
Authors: MacCABE JAMES H. , SIMON HELEN , ZANELLI JOLANTA W. , WALWYN REBECCA , McDONALD COLM D. , MURRAY ROBIN M. 
Published: July 2005

Background. Saccadic distractibility, as measured by the antisaccade task, has attracted attention as a putative endophenotypic marker for schizophrenia. Some studies have suggested that this measure is elevated in the unaffected relatives of schizophrenia patients. However, recent studies have called this into question and the topic remains controversial.Method. Saccadic distractibility was measured in 53 patients with DSM-IV schizophrenia, 80 unaffected first-degree relatives and 41 unaffected controls.Results. Schizophrenia patients performed worse than relatives and controls combined (p<0·00001), but relatives did not differ significantly from controls. Performance in multiply affected families was no worse than that in singly affected families. Relatives with a high presumed genetic risk for schizophrenia performed no worse than other relatives. The performance of the patients did not predict that of their relatives.Conclusions. These results demonstrate that saccadic distractibility is strongly associated with disease status but not with genetic loading for schizophrenia. We conclude that saccadic distractibility is unlikely to be useful as an endophenotypic marker in schizophrenia.
Molecular constituents of the postsynaptic density fraction revealed by proteomic analysis using multidimensional liquid chromatography‐tandem mass spectrometry
Authors: Yoshimura Yoshiyuki , Yamauchi Yoshio , Shinkawa Takashi , Taoka Masato , Donai Hitomi , Takahashi Nobuhiro , Isobe Toshiaki , Yamauchi Takashi 
Published: July 2005

AbstractProtein constituents of the postsynaptic density (PSD) fraction were analysed using an integrated liquid chromatography (LC)‐based protein identification system, which was constructed by coupling microscale two‐dimensional liquid chromatography (2DLC) with electrospray ionization (ESI) tandem mass spectrometry (MS/MS) and an automated data analysis system. The PSD fraction prepared from rat forebrain was solubilized in 6 m guanidium hydrochloride, and the proteins were digested with trypsin after S‐carbamoylmethylation under reducing conditions. The tryptic peptide mixture was then analysed with the 2DLC‐MS/MS system in a data‐dependent mode, and the resultant spectral data were automatically processed to search a genome sequence database for protein identification. In triplicate analyses, the system allowed assignments of 5264 peptides, which could finally be attributed to 492 proteins. The PSD contained various proteins involved in signalling transduction, including receptors, ion channel proteins, protein kinases and phosphatases, G‐protein and related proteins, scaffold proteins, and adaptor proteins. Structural proteins, including membrane proteins involved in cell adhesion and cell–cell interaction, proteins involved in endocytosis, motor proteins, and cytoskeletal proteins were also abundant. These results provide basic data on a major protein set associated with the PSD and a basis for future functional studies of this important neural machinery.
Proteasome inhibition and aggregation in Parkinson's disease: a comparative study in untransfected and transfected cells
Authors: Biasini Emiliano , Fioriti Luana , Ceglia Ilaria , Invernizzi Roberto , Bertoli Alessandro , Chiesa Roberto , Forloni Gianluigi 
Published: July 2005

AbstractDysfunction of the ubiquitin‐proteasome system (UPS) has been implicated in Parkinson's disease (PD) and other neurodegenerative disorders. We have investigated the effect of UPS inhibition on the metabolism of α‐synuclein (SYN) and parkin, two proteins genetically and histopathologically associated to PD. Pharmacological inhibition of proteasome induced accumulation of both parkin and SYN in transfected PC12 cells. We found that this effect was caused by increased protein synthesis rather than impairment of protein degradation, suggesting that inhibition of the UPS might lead to non‐specific up‐regulation of cytomegalovirus (CMV)‐driven transcription. To investigate whether endogenous parkin and SYN can be substrate of the UPS, untransfected PC12 cells and primary mesencephalic neurones were exposed to proteasome inhibitors, and parkin and SYN expression was evaluated at both protein and mRNA level. Under these conditions, we found that proteasome inhibitors did not affect the level of endogenous parkin and SYN. However, we confirmed that dopaminergic neurones were selectively vulnerable to the toxicity of proteasome inhibitors. Our results indicate that studies involving the use of proteasome inhibitors, particularly those in which proteins are expressed from a heterologous promoter, are subjected to potential artefacts that need to be considered for the interpretation of the role of UPS in PD pathogenesis.
Up‐regulation of NMDAR1 subunit gene expression in cortical neurons via a PKA‐dependent pathway
Authors: Lau Garrick C. , Saha Shamol , Faris Ramona , Russek Shelley J. 
Published: July 2005

AbstractTranscription mediated by protein kinase A and the cAMP response element binding protein (CREB) has been linked to the establishment of long‐term memory and cell survival. However, all of the major targets for activated CREB have yet to be identified. Given the fact that CREB‐mediated transcription is intimately involved in cellular processes of learning and memory and that CREB activity can be regulated by synaptic N‐methyl‐d‐aspartate receptors (NMDARs) and metabotropic GABA receptors, we have studied the role of the cAMP‐dependent signaling pathway in the regulation of the NMDA receptor subunit 1 (NMDAR1), a subunit required for functional receptor formation. We now report that levels of NMDAR1 subunit protein in primary neocortical cultures are increased 66% in response to forskolin, an activator of adenylyl cyclase. Up‐regulation of NMDAR1 is paralleled by a twofold increase in mRNA levels and an 83% increase in NMDAR1 promoter/luciferase reporter activity that is dependent on protein kinase A. Three cAMP regulatory elements (CREs) in the rat NMDAR1 promoter (− 228, − 67, and − 39) bind CREB in vitro and forskolin increases binding to two of the sites (− 228 and – 67). Chromatin immunoprecipitation of neuronal rat genomic DNA reveals that CREB is bound in vivo to the endogenous NMDAR1 gene. Increased presence of the activated Ser133 phosphorylated form is dependent on the length of exposure to forskolin. Taken together with the results of mutational analysis, the findings strongly suggest that transcription of NMDAR1 is regulated by the c‐AMP signaling pathway, most likely through the binding of CREB and its activation by signal‐dependent phosphorylation.
Reduced contribution from Na+/H+ exchange to acid extrusion during anoxia in adult rat hippocampal CA1 neurons
Authors: Sheldon Claire , Church John 
Published: July 2005

AbstractThe effect of anoxia on Na+/H+ exchange activity was examined in acutely isolated adult rat hippocampal CA1 neurons loaded with the H+‐sensitive fluorophore, BCECF. Five‐minute anoxia imposed under nominally HCO3–/CO2‐free conditions induced a fall in pHi, the magnitude of which was smaller following prolonged exposure to medium in which N‐methyl‐d‐glucamine (NMDG+) was employed as an extracellular Na+ (Na+o) substitute. Also consistent with the possibility that Na+/H+ exchange becomes inhibited soon after the induction of anoxia, rates of Na+o‐dependent pHi recovery from internal acid loads imposed during anoxia were slowed, compared to rates of Na+o‐dependent pHi recovery observed prior to anoxia. At the time at which rates of pHi recovery were reduced during anoxia, cellular adenosine triphosphate (ATP) levels had fallen to 35% of preanoxic levels, suggesting that ATP depletion might contribute to the observed inhibition of Na+/H+ exchange. In support, incubation of neurons with 2‐deoxyglucose and antimycin A under normoxic conditions induced a fall in cellular ATP levels that was also associated with reduced Na+o‐dependent rates of pHi recovery from imposed acid loads; conversely, pre‐treatment with 10 mm creatine attenuated the effects of anoxia to reduce both ATP levels and Na+o‐dependent rates of pHi recovery from internal acid loads. Taken together, the results are consistent with the possibility that functional Na+/H+ exchange activity in adult rat CA1 neurons declines soon after the onset of anoxia, possibly as a result of anoxia‐induced falls in intracellular ATP.
Secretion of locally synthesized neurohormone from neurites of peptidergic neurons
Authors: Lee Wenjau , Wayne Nancy L. 
Published: July 2005

AbstractLocal protein synthesis in neuronal processes is a common phenomenon and may play an important role in synaptic plasticity and hormonal regulation. We have used neuroendocrine bag cells of Aplysia californica as a model system to study local protein synthesis. In our previous work we found that bag cell neurites are capable of synthesizing and processing the prohormone of egg‐laying hormone (pro‐ELH). In the present study, we found that bag cell neurites are also capable of releasing locally synthesized pro‐ELH and ELH‐related products via both constitutive and regulated pathways. However, an electrical afterdischarge did not enhance local pro‐ELH synthesis, as it does in the bag cell soma. This is the first evidence that isolated neurites are capable of secreting locally synthesized proteins.
Endogenous mitochondrial oxidative stress: neurodegeneration, proteomic analysis, specific respiratory chain defects, and efficacious antioxidant therapy in superoxide dismutase 2 null mice
Authors: Hinerfeld Douglas , Traini Mathew D. , Weinberger Ron P. , Cochran Bruce , Doctrow Susan R. , Harry Jenny , Melov Simon 
Published: July 2005

AbstractOxidative stress and mitochondrial dysfunction have been linked to neurodegenerative disorders such as Parkinson's and Alzheimer's disease. However, it is not yet understood how endogenous mitochondrial oxidative stress may result in mitochondrial dysfunction. Most prior studies have tested oxidative stress paradigms in mitochondria through either chemical inhibition of specific components of the respiratory chain, or adding an exogenous insult such as hydrogen peroxide or paraquat to directly damage mitochondria. In contrast, mice that lack mitochondrial superoxide dismutase (SOD2 null mice) represent a model of endogenous oxidative stress. SOD2 null mice develop a severe neurological phenotype that includes behavioral defects, a severe spongiform encephalopathy, and a decrease in mitochondrial aconitase activity. We tested the hypothesis that specific components of the respiratory chain in the brain were differentially sensitive to mitochondrial oxidative stress, and whether such sensitivity would lead to neuronal cell death. We carried out proteomic differential display and examined the activities of respiratory chain complexes I, II, III, IV, V, and the tricarboxylic acid cycle enzymes alpha‐ketoglutarate dehydrogenase and citrate synthase in SOD2 null mice in conjunction with efficacious antioxidant treatment and observed differential sensitivities of mitochondrial proteins to oxidative stress. In addition, we observed a striking pattern of neuronal cell death as a result of mitochondrial oxidative stress, and were able to significantly reduce the loss of neurons via antioxidant treatment.