bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac cholinergic NO-cGMP signaling following acute myocardial infarction and nNOS gene transfer
Authors: Dawson T. A. , Li D. , Woodward T. , Barber Z. , Wang L. , Paterson D. J.
Published: July 2008

Myocardial infarction (MI) is associated with oxidative stress, which may cause cardiac autonomic impairment. We tested the hypothesis that acute MI disrupts cardiac cholinergic signaling by impairing nitric oxide (NO)-cGMP modulation of acetylcholine (ACh) release and whether the restoration of this pathway following cardiac neuronal NO synthase (nNOS) gene transfer had any bearing on the neural phenotype. Guinea pigs underwent four ligature coronary artery surgery ( n = 50) under general anesthesia to induce MI or sham surgery ( n = 32). In a separate group, at the time of MI surgery, adenovirus encoding nNOS ( n = 29) or enhanced green fluorescent protein (eGFP; n = 30) was injected directly into the right atria, where the postganglionic cholinergic neurons reside. In vitro-evoked right atrial [3H]ACh release, right atrial NOS activity, and cGMP levels were measured at 3 days. Post-MI 24% of guinea pigs died compared with 9% in the sham-operated group. Evoked right atrial [3H]ACh release was significantly ( P < 0.05) decreased in the MI group as was NOS activity and cGMP levels. Tetrahydrobiopterin levels were not significantly different between the sham and MI groups. Infarct sizes between gene-transferred groups were not significantly different. The nNOS transduced group had significantly increased right atrial [3H]ACh release, right atrial NOS activity, cGMP levels, and decreased cAMP levels. Fourteen percent of the nNOS transduced animals died compared with 31% mortality in the MI + eGFP group at 3 days. In conclusion, cardiac nNOS gene transfer partially restores the defective NO-cGMP cholinergic pathway post-MI, which was associated with a trend of improved survival at 3 days.
Conditioning the heart induces formation of signalosomes that interact with mitochondria to open mitoKATPchannels
Authors: Quinlan Casey L. , Costa Alexandre D. T. , Costa Cinthia L. , Pierre Sandrine V. , Dos Santos Pierre , Garlid Keith D.
Published: July 2008

Perfusion of the heart with bradykinin triggers cellular signaling events that ultimately cause opening of mitochondrial ATP-sensitive K+(mitoKATP) channels, increased H2O2production, inhibition of the mitochondrial permeability transition (MPT), and cardioprotection. We hypothesized that the interaction of bradykinin with its receptor induces the assembly of a caveolar signaling platform (signalosome) that contains the enzymes of the signaling pathway and that migrates to mitochondria to induce mitoKATPchannel opening. We developed a novel method for isolating and purifying signalosomes from Langendorff-perfused rat hearts treated with bradykinin. Fractions containing the signalosomes were found to open mitoKATPchannels in mitochondria isolated from untreated hearts via the activation of mitochondrial PKC-ε. mitoKATPchannel opening required signalosome-dependent phosphorylation of an outer membrane protein. Immunodetection analysis revealed the presence of the bradykinin B2receptor only in the fraction isolated from bradykinin-treated hearts. Immunodetection and immunogold labeling of caveolin-3, as well as sensitivity to cholesterol depletion and resistance to Triton X-100, attested to the caveolar nature of the signalosomes. Ischemic preconditioning, ischemic postconditioning, and perfusion with ouabain also led to active signalosome fractions that opened mitoKATPchannels in mitochondria from untreated hearts. These results provide initial support for a novel mechanism for signal transmission from a plasma membrane receptor to mitoKATPchannels.
Strain distribution over plaques in human coronary arteries relates to shear stress
Authors: Gijsen Frank J. H. , Wentzel Jolanda J. , Thury Attila , Mastik Frits , Schaar Johannes A. , Schuurbiers Johan C. H. , Slager Cornelis J. , van der Giessen Wim J. , de Feyter Pim J. , van der Steen Anton F. W. , Serruys Patrick W.
Published: July 2008

Once plaques intrude into the lumen, the shear stress they are exposed to alters with hitherto unknown consequences for plaque composition. We investigated the relationship between shear stress and strain, a marker for plaque composition, in human coronary arteries. We imaged 31 plaques in coronary arteries with angiography and intravascular ultrasound. Computational fluid dynamics was used to obtain shear stress. Palpography was applied to measure strain. Each plaque was divided into four regions: upstream, throat, shoulder, and downstream. Average shear stress and strain were determined in each region. Shear stress in the upstream, shoulder, throat, and downstream region was 2.55 ± 0.89, 2.07 ± 0.98, 2.32 ± 1.11, and 0.67 ± 0.35 Pa, respectively. Shear stress in the downstream region was significantly lower. Strain in the downstream region was also significantly lower than the values in the other regions (0.23 ± 0.08% vs. 0.48 ± 0.15%, 0.43 ± 0.17%, and 0.47 ± 0.12%, for the upstream, shoulder, and throat regions, respectively). Pooling all regions, dividing shear stress per plaque into tertiles, and computing average strain showed a positive correlation; for low, medium, and high shear stress, strain was 0.23 ± 0.10%, 0.40 ± 0.15%, and 0.60 ± 0.18%, respectively. Low strain colocalizes with low shear stress downstream of plaques. Higher strain can be found in all other plaque regions, with the highest strain found in regions exposed to the highest shear stresses. This indicates that high shear stress might destabilize plaques, which could lead to plaque rupture.
Toward a noninvasive subject-specific estimation of abdominal aortic pressure
Authors: Thore Carl-Johan , Stålhand Jonas , Karlsson Matts
Published: July 2008

A method for estimation of central arterial pressure based on linear one-dimensional wave propagation theory is presented in this paper. The equations are applied to a distributed model of the arterial tree, truncated by three-element windkessels. To reflect individual differences in the properties of the arterial trees, we pose a minimization problem from which individual parameters are identified. The idea is to take a measured waveform in a peripheral artery and use it as input to the model. The model subsequently predicts the corresponding waveform in another peripheral artery in which a measurement has also been made, and the arterial tree model is then calibrated in such a way that the computed waveform matches its measured counterpart. For the purpose of validation, invasively recorded abdominal aortic, brachial, and femoral pressures in nine healthy subjects are used. The results show that the proposed method estimates the abdominal aortic pressure wave with good accuracy. The root mean square error (RMSE) of the estimated waveforms was 1.61 ± 0.73 mmHg, whereas the errors in systolic and pulse pressure were 2.32 ± 1.74 and 3.73 ± 2.04 mmHg, respectively. These results are compared with another recently proposed method based on a signal processing technique, and it is shown that our method yields a significantly ( P < 0.01) lower RMSE. With more extensive validation, the method may eventually be used in clinical practice to provide detailed, almost individual, specific information as a valuable basis for decision making.
Animal models of acute lung injury
Authors: Matute-Bello Gustavo , Frevert Charles W. , Martin Thomas R.
Published: July 2008

Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.
Phospholipase D signaling in serotonin-induced mitogenesis of pulmonary artery smooth muscle cells
Authors: Liu Y. , Fanburg B. L.
Published: July 2008

We have previously reported the participation of mitogen-activated protein, Rho, and phosphoinositide-3 (PI3) kinases in separate pathways in serotonin (5-HT)-induced proliferation of pulmonary artery smooth muscle cells (SMCs). In this study, we investigated the possible participation of phospholipase D (PLD) and phosphatidic acid (PA) in this growth process. 5-HT stimulated a time-dependent increase in [3H]phosphatidylbutanol and PA generation. Exposure of SMCs to 1-butanol or overexpression of an inactive mutant of human PLD1R898R blocked 5-HT-induced proliferation. Furthermore, 1-butanol inhibited 5-HT activation of S6K1 and S6 protein, downstream effectors of mammalian target of rapamycin (mTOR), by 80 and 72%, respectively, and partially blocked activation of extracellular signal-regulated kinase (ERK) by 30% but had no effect on other associated signaling pathways. Exogenous PA caused cellular proliferation and revitalized cyclin D1 expression by 5-HT of the 1-butanol-treated cells. PA also reproduced activations by 5-HT of mTOR, S6K1, and ERK. Transfection with inactive human PLD1 reduced 5-HT-induced activation of S6K1 by ∼50%. Inhibition of 5-HT receptor 2A (R 2A) with ketaserin blocked PLD activation by 5-HT. Inhibition with PI3-kinase inhibitor failed to block either activation of PLD by 5-HT or PA-dependent S6K1 phosphorylation. Taken together, these results indicate that ligation of the 5-HTR 2A by 5-HT initiates PLD activation in SMCs, and that its product, PA, is an early signaling molecule in 5-HT-induced pulmonary artery SMC proliferation. Signaling by PA produces its downstream effects primarily through the mTOR/S6K1 pathway and to a lesser extent through the ERK pathway. Hydrolysis of cell membrane lipid may be important in vascular effects of 5-HT.
Innate immune responses in murine pleural mesothelial cells: Toll-like receptor-2 dependent induction of β-defensin-2 by staphylococcal peptidoglycan
Authors: Hussain Tajamul , Nasreen Najmunnisa , Lai Yimu , Bellew Brendan F. , Antony Veena B. , Mohammed Kamal A.
Published: July 2008

The innate immune response is mediated in part by pattern recognition receptors including Toll-like receptors (TLRs). The pleural mesothelial cells (PMCs) that line the pleural surface are in direct contact with pleural fluid and accordingly carry the risk of exposure to infiltrating microorganisms or their components in an event of a complicated parapneumonic effusion. Here we show that murine primary PMCs constitutively express TLR-1 through TLR-9 and, upon activation with peptidoglycan (PGN), mouse PMC produce antimicrobial peptide β-defensin-2 (mBD-2). Treatment of PMCs with staphylococcal PGN, a gram-positive bacterial cell wall component and a TLR-2 agonist, resulted in a significant increase in TLR-2 and mBD-2 expression. Silencing of TLR-2 expression by small interfering RNA led to the downregulation of PGN-induced mBD-2 expression, thereby establishing causal relationship between the activation of TLR-2 receptor and mBD-2 production. PMCs exposed to PGN showed increased p38 MAPK activity. In addition, PGN-induced mBD-2 expression was attenuated by SB203580, a p38 MAPK inhibitor, underlining the importance of p38 MAPK in mBD-2 induction. Inhibition of erk1/erk2 or phosphatidylinositol 3-kinase did not block PGN-induced mBD-2 expression in PMC. PGN-activated PMC-derived mBD-2 significantly killed Staphylococcus aureus, and mBD-2-neutralizing antibodies blunted this antimicrobial activity. Taken together, these data indicate that PMCs may contribute to host innate immune defense upon exposure to gram-positive bacteria or their products within the pleural space by upregulating TLR-2 and mBD-2 expression.
Alveolar epithelial cell injury with Epstein-Barr virus upregulates TGFβ1 expression
Authors: Malizia Andrea P. , Keating Dominic T. , Smith Sinead M. , Walls Dermot , Doran Peter P. , Egan Jim J.
Published: July 2008

Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation, and ECM protein deposition. Epstein-Barr virus (EBV) has previously been localized to alveolar epithelial cells of IPF patients and is associated with a poor prognosis. In this study, we utilized a microarray-based differential gene expression analysis strategy to identify molecular drivers of EBV-associated lung fibrosis. Two cell lines, primary human alveolar epithelial cells type 2 and A549 cells, were infected with EBV. EBV lytic phase induction increased active and total transforming growth factor-β1 (TGFβ1) transcript expression in association with reduced cell proliferation and increased caspase 3/7 activity. Exposing EBV-infected cells to ganciclovir resulted in TGFβ1 deregulation and reduced expression of EBV early response genes, BRLF1 and BZLF1. We targeted the BRLF1 and BZLF1 gene products, Rta and Zta, by silencing RNA, and this resulted in the normalization of TGFβ1 transcript and cell proliferation levels. Our study using a viral cell line model complements existing human and animal model data and further provides evidence to suggest that viral epithelial cell injury may play a role in IPF.
Cytokine-induced arginase activity in pulmonary endothelial cells is dependent on Src family tyrosine kinase activity
Authors: Chang Rossana , Chicoine Louis G. , Cui Hongmei , Kanagy Nancy L. , Walker Benjimen R. , Liu Yusen , English B. Keith , Nelin Leif D.
Published: July 2008

We hypothesized that the Src family tyrosine kinases (STKs) are involved in the upregulation of arginase and inducible nitric oxide synthase (iNOS) expression in response to inflammatory stimuli in pulmonary endothelial cells. Treatment of bovine pulmonary arterial endothelial cells (bPAEC) with lipopolysaccharide and tumor necrosis factor-α (L/T) resulted in increased urea and nitric oxide (NO) production, and this increase in urea and NO production was inhibited by the STK inhibitor PP1 (10 μM). The STK inhibitors PP2 (10 μM) and herbimycin A (10 μM) also prevented the L/T-induced expression of both arginase II and iNOS mRNA in bPAEC. Together, the data demonstrate a central role of STK in the upregulation of both arginase II and iNOS in bPAEC in response to L/T treatment. To identify the specific kinase(s) required for the induction of urea and NO production, we studied human pulmonary microvascular endothelial cells (hPMVEC) so that short interfering RNA (siRNA) techniques could be employed. We found that hPMVEC express Fyn, Yes, c-Src, Lyn, and Blk and that the protein expression of Fyn, Yes, c-Src, and Lyn could be inhibited with specific siRNA. The siRNA targeting Fyn prevented the cytokine-induced increase in urea and NO production, whereas siRNAs specifically targeting Yes, c-Src, and Lyn had no appreciable effect on cytokine-induced urea and NO production. These findings support our hypothesis that inflammatory stimuli lead to increased urea and NO production through a STK-mediated pathway. Furthermore, these results indicate that the STK Fyn plays a critical role in this process.
Chronic intrauterine pulmonary hypertension increases endothelial cell Rho kinase activity and impairs angiogenesis in vitro
Authors: Gien Jason , Seedorf Gregory J. , Balasubramaniam Vivek , Tseng Nancy , Markham Neil , Abman Steven H.
Published: July 2008

Persistent pulmonary hypertension of the newborn (PPHN) is characterized by endothelial dysfunction and decreased vascular growth. The role of Rho kinase activity in modulating endothelial function and regulating angiogenesis during normal lung development and in PPHN is unknown. We hypothesized that PPHN increases Rho kinase activity in fetal pulmonary artery endothelial cells (PAECs) and impairs angiogenesis in vitro. Proximal PAECs were harvested from fetal sheep with partial ligation of the ductus arteriosus in utero (PPHN) and age-matched controls. Rho kinase activity was measured by RhoA, Rho GTP, and phosphorylated MYPT-1 protein content. The effects of Rho kinase activity on angiogenesis, endothelial nitric oxide (NO) synthase (eNOS) protein expression, and NO production were determined in normal and PPHN PAECs. Angiogenesis was assessed by tube formation in vitro with/without Y-27632 (a Rho kinase inhibitor) and calpeptin (a Rho kinase activator) in the presence/absence of N-nitro-l-arginine (l-NA, an NOS inhibitor). RhoA, Rho GTP, and phosphorylated MYPT-1 protein were increased in PPHN PAECs. Tube formation was reduced 29% in PPHN PAECs ( P < 0.001) and increased with Y-27632 treatment in normal and PPHN PAECs, with PPHN PAECs achieving levels similar to those of normal PAECs. l-NA inhibited the Y-27632-induced increase in tube formation in normal, but not PPHN, PAECs. Calpeptin reduced tube formation in normal and PPHN PAECs. eNOS expression was reduced 42% in PPHN PAECs ( P < 0.01). Y-27632 increased eNOS protein and NO production in normal and PPHN PAECs. Calpeptin decreased eNOS protein only in normal PAECs but reduced NO production in normal and PPHN PAECs. We conclude that Rho kinase activity is increased in PPHN PAECs and impairs angiogenesis and downregulates eNOS protein and NO production in vitro.
Genesis and Regulation of the Heart Automaticity
Authors: Mangoni Matteo E. , Nargeot Joël
Published: July 2008

The heart automaticity is a fundamental physiological function in higher organisms. The spontaneous activity is initiated by specialized populations of cardiac cells generating periodical electrical oscillations. The exact cascade of steps initiating the pacemaker cycle in automatic cells has not yet been entirely elucidated. Nevertheless, ion channels and intracellular Ca2+signaling are necessary for the proper setting of the pacemaker mechanism. Here, we review the current knowledge on the cellular mechanisms underlying the generation and regulation of cardiac automaticity. We discuss evidence on the functional role of different families of ion channels in cardiac pacemaking and review recent results obtained on genetically engineered mouse strains displaying dysfunction in heart automaticity. Beside ion channels, intracellular Ca2+release has been indicated as an important mechanism for promoting automaticity at rest as well as for acceleration of the heart rate under sympathetic nerve input. The potential links between the activity of ion channels and Ca2+release will be discussed with the aim to propose an integrated framework of the mechanism of automaticity.
Intracellular Transport and Kinesin Superfamily Proteins, KIFs: Structure, Function, and Dynamics
Authors: Hirokawa Nobutaka , Noda Yasuko
Published: July 2008

Various molecular cell biology and molecular genetic approaches have indicated significant roles for kinesin superfamily proteins (KIFs) in intracellular transport and have shown that they are critical for cellular morphogenesis, functioning, and survival. KIFs not only transport various membrane organelles, protein complexes, and mRNAs for the maintenance of basic cellular activity, but also play significant roles for various mechanisms fundamental for life, such as brain wiring, higher brain functions such as memory and learning and activity-dependent neuronal survival during brain development, and for the determination of important developmental processes such as left-right asymmetry formation and suppression of tumorigenesis. Accumulating data have revealed a molecular mechanism of cargo recognition involving scaffolding or adaptor protein complexes. Intramolecular folding and phosphorylation also regulate the binding activity of motor proteins. New techniques using molecular biophysics, cryoelectron microscopy, and X-ray crystallography have detected structural changes in motor proteins, synchronized with ATP hydrolysis cycles, leading to the development of independent models of monomer and dimer motors for processive movement along microtubules.
Evolution and Function of the ADP Ribosyl Cyclase/CD38 Gene Family in Physiology and Pathology
Authors: Malavasi Fabio , Deaglio Silvia , Funaro Ada , Ferrero Enza , Horenstein Alberto L. , Ortolan Erika , Vaisitti Tiziana , Aydin Semra
Published: July 2008

The membrane proteins CD38 and CD157 belong to an evolutionarily conserved family of enzymes that play crucial roles in human physiology. Expressed in distinct patterns in most tissues, CD38 (and CD157) cleaves NAD+and NADP+, generating cyclic ADP ribose (cADPR), NAADP, and ADPR. These reaction products are essential for the regulation of intracellular Ca2+, the most ancient and universal cell signaling system. The entire family of enzymes controls complex processes, including egg fertilization, cell activation and proliferation, muscle contraction, hormone secretion, and immune responses. Over the course of evolution, the molecules have developed the ability to interact laterally and frontally with other surface proteins and have acquired receptor-like features. As detailed in this review, the loss of CD38 function is associated with impaired immune responses, metabolic disturbances, and behavioral modifications in mice. CD38 is a powerful disease marker for human leukemias and myelomas, is directly involved in the pathogenesis and outcome of human immunodeficiency virus infection and chronic lymphocytic leukemia, and controls insulin release and the development of diabetes. Here, the data concerning diseases are examined in view of potential clinical applications in diagnosis, prognosis, and therapy. The concluding remarks try to frame all of the currently available information within a unified working model that takes into account both the enzymatic and receptorial functions of the molecules.
Activity-Dependent Structural and Functional Plasticity of Astrocyte-Neuron Interactions
Authors: Theodosis Dionysia T. , Poulain Dominique A. , Oliet Stéphane H. R.
Published: July 2008

Observations from different brain areas have established that the adult nervous system can undergo significant experience-related structural changes throughout life. Less familiar is the notion that morphological plasticity affects not only neurons but glial cells as well. Yet there is abundant evidence showing that astrocytes, the most numerous cells in the mammalian brain, are highly mobile. Under physiological conditions as different as reproduction, sensory stimulation, and learning, they display a remarkable structural plasticity, particularly conspicuous at the level of their lamellate distal processes that normally ensheath all portions of neurons. Distal astrocytic processes can undergo morphological changes in a matter of minutes, a remodeling that modifies the geometry and diffusion properties of the extracellular space and relationships with adjacent neuronal elements, especially synapses. Astrocytes respond to neuronal activity via ion channels, neurotransmitter receptors, and transporters on their processes; they transmit information via release of neuroactive substances. Where astrocytic processes are mobile then, astrocytic-neuronal interactions become highly dynamic, a plasticity that has important functional consequences since it modifies extracellular ionic homeostasis, neurotransmission, gliotransmission, and ultimately neuronal function at the cellular and system levels. Although a complete picture of intervening cellular mechanisms is lacking, some have been identified, notably certain permissive molecular factors common to systems capable of remodeling (cell surface and extracellular matrix adhesion molecules, cytoskeletal proteins) and molecules that appear specific to each system (neuropeptides, neurotransmitters, steroids, growth factors) that trigger or reverse the morphological changes.
Histamine in the Nervous System
Authors: Haas Helmut L. , Sergeeva Olga A. , Selbach Oliver
Published: July 2008

Histamine is a transmitter in the nervous system and a signaling molecule in the gut, the skin, and the immune system. Histaminergic neurons in mammalian brain are located exclusively in the tuberomamillary nucleus of the posterior hypothalamus and send their axons all over the central nervous system. Active solely during waking, they maintain wakefulness and attention. Three of the four known histamine receptors and binding to glutamate NMDA receptors serve multiple functions in the brain, particularly control of excitability and plasticity. H1 and H2 receptor-mediated actions are mostly excitatory; H3 receptors act as inhibitory auto- and heteroreceptors. Mutual interactions with other transmitter systems form a network that links basic homeostatic and higher brain functions, including sleep-wake regulation, circadian and feeding rhythms, immunity, learning, and memory in health and disease.
The Impact of Vaccines in Low- and High-Income Countries
Authors: Gothefors Leif
Published: July 2008

Vaccination has become the most effective public health measure for the control of infectious diseases after the provision of clean drinking water. The history of vaccination is marked with great hopes and some disappointments. In particular, the second half of the 20th century witnessed the development of remarkable vaccination projects. There is a possibility that polio and measles may be eradicated within a few years, but almost 3 million people – usually children <5 years of age – die each year from diseases that are preventable by vaccines. Developing countries are struggling to get the vaccines to children who desperately need them. However, in Europe and North America, people have become complacent about vaccines: ‘these diseases are no longer a threat and the vaccine is more dangerous than the disease’. Those misconceptions have caused outbreaks of measles, diphtheria and pertussis. The international community must continue to devote the necessary resources, money and manpower to fully exploit the promise that vaccines hold for the relief of human misery.
Determinants of Responses to Oral Vaccines in Developing Countries
Authors: Sack David A. , Qadri Firdausi , Svennerholm Ann-Mari
Published: July 2008

Oral vaccines which are intended for global use do not necessarily induce the same immune responses in all children worldwide. In fact, several vaccines often induce less frequent and lower mean antibody responses in children in developing countries, suggesting that the vaccines may be less protective among children in these areas. Though the reasons for this less vigorous response are not completely understood, it appears that nutrition-related factors, including both protein-calorie and micronutrient malnutrition, are important aspects in understanding the hyporesponsiveness seen in these children. Related issues including breastfeeding, interference from maternal placental antibodies, intestinal parasitic infections, intestinal mucosal damage and possibly maternal malnutrition during pregnancy also appear to be important. Vaccines designed for oral administration will need to be adjusted to these potential problems in order to maximize benefits for all children. Oral vaccines, when given to children in developing countries, may require higher doses of vaccine, booster doses, calorie, micronutrient and vitamin supplements, withdrawal of breast milk before vaccine administration, deworming medications or other measures to realize their full benefit.
Effects of Diameter, Number and Tightness of Sutures on Pancreatic Injury Response
Authors: Lämsä Teemu , Jin Hai-Tao , Nordback Panu H. , Sand Juhani , Nordback Isto
Published: July 2008

Background: We have experimental data indicating that the pancreas is easily damaged by any intervention. The present study compared the effects of suture diameter, number of needle passes and suture tightness on rat pancreas. Methods: Under anesthesia, rat pancreas was sutured either with one loose stitch of 6-0 polydioxanone (PDS II) or 3-0 PDS II, with 5 passes of loose running 6-0 PDS II, or with 6-0 PDS II loop tightened to 0.6 or 1.2 N. Amylase activity and pancreatic tissue histology at the suturing site and farther away, were evaluated 1, 3, 7 and 21 days postoperatively. Results: Each suturing exposure and the sham-operation induced temporary amylase activity elevation on day 1 when compared with the baseline. In histology, 3-0 suture, 5 needle passes and 1.2-newton loop induced more damage than 6-0 suture, single needle pass and 0.6-newton loop, respectively. Similar but milder changes were observed in samples from the remote site. Conclusions: The pancreas reacts to suturing with widespread injury response resembling that of acute pancreatitis. In attempting to reduce suturing-induced widespread injury, as few and thin sutures and as loose suture tightness as possible should be used. Although these findings may seem obvious, they have not previously been proven in terms of histology.
Encephalitis Lethargica in the Soviet Union
Authors: Vilensky Joel A. , Mukhamedzyanov Ravil Z. , Gilman Sid
Published: July 2008

Although encephalitis lethargica (EL) appeared in epidemic form in the Soviet Union during the 1920s as it did in most of the world, the Western literature, particularly English, contains little information about the manifestations of the disease there. Here we summarize articles by prominent Russian neurologists who wrote about the disease as they viewed it during the epidemic period. As in the West, Russian clinicians found EL to be remarkably polymorphic, although some signs and symptoms, especially those pertaining to the psychological aspects of the disease, seemed to be more prevalent or were described better and perhaps more frequently by these clinicians. Some Russian clinicians emphasized an increased prevalence of EL among Jews and a relationship with illness and trauma, whereas others found strong evidence for contagion, especially in rural areas.
Stenting of Symptomatic Basilar and Vertebral Artery Stenosis in Patients Resistant to Optimal Medical Prevention: The Lyon Stroke Unit Experience
Authors: Ralea Ionela-Camelia , Nighoghossian Norbert , Tahon Florence , Derex Laurent , Cakmak Serkan , Trouillas Paul , Turjman Francis
Published: July 2008

Intracranial angioplasty stenting may be an efficient therapy in patients with intracranial atherosclerotic symptomatic vertebrobasilar artery stenosis unresponsive to optimal medical therapy. We present our experience in this setting. Results: The study included 12 cases (8 men, 4 women), with an age range of 43–78 years (mean 62.6 years). Intracranial stenosis that resulted in qualifying stroke or transient ischemic attack involved the vertebral artery (n = 4), lower basilar artery (n = 1) and mid basilar artery (n = 5). Tandem stenosis included the intracranial vertebral artery and basilar artery (n = 1) and both intracranial vertebral arteries (n = 1). The degree of stenosis ranged between 70 and 90% in the basilar and vertebral arteries. Angioplasty + stenting was performed in all lesions. A successful procedure resulting in 30% of residual stenosis was found in 14 vessels. A periprocedural adverse event occurred in 1 case and was related to a brain hemorrhage. The mean patient follow-up was 15 ± 3 months; 10 patients remained symptom free. All patients underwent a percutaneous endovascular balloon angioplasty and stent placement. Conclusions:This study supports the safety and the potential efficiency of stent-assisted angioplasty in patients resistant to optimal prevention. Randomized larger prospective trials are needed to confirm the benefit of this approach.
Neurological and MRI Findings as Predictors of Progressive-Type Lacunar Infarction
Authors: Nagakane Yoshinari , Naritomi Hiroaki , Oe Hiroshi , Nagatsuka Kazuyuki , Yamawaki Takemori
Published: July 2008

Aims: To find neurological or neuroimaging signs to predict neurological deterioration in acute lacunar infarctions. Methods: Sixty-one consecutive patients with a supratentorial lacunar infarct, who were admitted within 48 h, were studied retrospectively. Progressive-type stroke (PS) was defined as progressive motor deficits that arose within 7 days after onset, by using the motor ratings of the National Institutes of Health Stroke Scale. Results: Sixteen patients (26%) were classified into the PS group. In the PS group, fluctuating or progressing onset (81 vs. 42%, p = 0.009), leg-predominant motor deficits on admission (63 vs. 16%, p = 0.001) and corona radiata lesion on diffusion-weighted MRI (100 vs. 69%, p = 0.013) were all more frequent than in the non-PS group. Conclusion: Bedside neurological assessment and MRI findings may allow us to predict PS and start early intensive treatment for preventing further neurological deterioration.
Cognitive Impairment in Late-Onset Depression
Authors: Delaloye C. , Baudois S. , de Bilbao F. , Dubois Remund C. , Hofer F. , Lamon M. , Ragno Paquier C. , Weber K. , Herrmann F.R. , Giardini U. , Giannakopoulos P.
Published: July 2008

Background: While cognitive dysfunction in late-onset depression (LOD) is common, the nature and determinants of this impairment are heterogeneous. It has been suggested that neuropsychological decrements in LOD patients might result from a deficit in processing resources. In order to address this issue, we analyzed processing resources in LOD to see if their decrease explains higher-level cognition (episodic memory and naming capacity) deficits. Methods: Measures of processing speed, working memory, inhibition, episodic memory and naming capacity were administered to 14 LOD inpatients and 14 controls. Results: The LOD patients performed significantly worse than the controls in all domains except for inhibition. Hierarchical regression analyses showed that naming capacity impairment was totally mediated by processing speed and working memory, whereas episodic memory dysfunction was only partially mediated by working memory. Conclusion: The reduction in certain processing resources (working memory, processing speed) in late-onset depressed patients appears to mediate impairments in episodic memory and naming capacity. However, episodic memory impairment cannot only be explained by processing resource decrement in LOD patients, suggesting that a primary episodic memory dysfunction is present in this condition.
Biliary Tract Complications after Liver Transplantation: A Review
Authors: Wojcicki Maciej , Milkiewicz Piotr , Silva Michael
Published: July 2008

Biliary complications continue to be a major cause of morbidity in liver transplant recipients with an incidence of 10–30% following whole-organ transplantation and a mortality rate of up to 10%. Biliary leaks and strictures are most common but sphincter of Oddi dysfunction, hemobilia, and biliary obstruction are also observed. Biliary complications may be related to various factors such as hepatic artery patency, preservation injury, cytomegalovirus infection, chronic ductopenic rejection, ABO incompatibility, and technical reasons. The latter include imperfect anastomosis, T-tube-related complications and the use of partial liver grafts when cut surface biliary leaks or inadvertent bile duct injuries may occur during parenchymal division. The usage of a T-tube for duct-to-duct anastomosis in whole-organ liver transplantation remains controversial, mainly because of the high rates of T-tube-related complications observed in many series. In this article we review the etiology, as well as the main types of biliary complications according to the technique of biliary reconstruction and liver transplant procedure performed. Their management is also discussed with interventional radiology and endoscopic techniques emerging as the preferred treatment option, obviating the need for surgery in a selected majority of patients.
Initiation of Oral Anticoagulation after Acute Ischaemic Stroke or Transient Ischaemic Attack: Timing and Complications of Overlapping Heparin or Conventional Treatment
Authors: Audebert Heinrich J. , Schenk Berit , Tietz Viola , Schenkel Johannes , Heuschmann Peter U.
Published: July 2008

Background: Oral anticoagulation is highly effective for secondary prevention of cardioembolic strokes in patients with atrial fibrillation (AF). There are no studies investigating timing and complications of different strategies for initiation of oral anticoagulation after acute stroke or transient ischaemic attack (TIA). Methods: Patients of ten community hospitals participating in the prospective evaluation of medical effects of the Telemedical Project for Integrative Stroke Care (TEMPiS) were included. This observational evaluation was restricted to ischaemic stroke or TIA patients with AF who were started on Phenprocoumon treatment during in-hospital stay. Antithrombotic co-medication was dichotomized in heparin bridging (weight or partial thromboplastin time-adjusted heparin) or conventional treatment (antiplatelets and/or low-dose heparin or nil). Besides treatment-relevant extracranial bleeding, major complications were documented according to the European Atrial Fibrillation Trial definitions including vascular death, ischaemic or haemorrhagic stroke, systemic embolism, and myocardial infarction. Results: Between July 2003 and March 2005, 4,082 ischaemic stroke or TIA patients were admitted. AF was recorded in 961 patients (23.5%), of whom 376 (39.1%) received oral anticoagulation. In 229 of these patients oral anticoagulation was started in hospital, 150 (65.5%) with heparin bridging and 79 (34.5%) with conventional treatment. Patients with heparin bridging were younger, and had a longer in-hospital stay after adjustment for potential confounders (p = 0.01). Major complications were infrequent in both groups (2.0 vs. 2.5%; p = 1.0) as well as extracranial bleeding (3.3 vs. 1.2%; p = 0.43). Conclusions: Initiation of oral anticoagulation after acute ischaemic stroke yielded low complication rates independent of antithrombotic co-medication. Heparin bridging was associated with a longer stay in acute care hospitals.
The Clinical Syndrome and Etiological Mechanism of Infarction Involving the Nucleus Prepositus Hypoglossi
Authors: Cho Hyun-Ji , Choi Hye-Yeon , Kim Young Dae , Seo Sang Won , Heo Ji Hoe
Published: July 2008

Background: The human nucleus prepositus hypoglossi (NPH), which is known to be a neural integrator of horizontal eye movement, may also serve vestibular function. The present study investigated the clinical spectrum and etiological mechanism of isolated, small infarctions involving the NPH area demonstrated on MRI. Methods: The subjects of this study were 18 consecutive patients with a small infarction involving the NPH that was demonstrated by diffusion-weighted MRI. We assessed their clinical features according to the level involved (pons or medulla oblongata) and determined etiological mechanisms that may cause infarction in this region. Results: Vertigo and nausea/vomiting were the presenting symptoms in all patients. Sixteen patients showed truncal ataxia (contralateral falls in 11 patients and bilateral falls in 3). Gaze-evoked nystagmus was observed in 13 patients. In addition to those NPH-related symptoms, ipsi- lateral peripheral facial palsy and horizontal gaze palsies, including internuclear ophthalmoplegia and horizontal conjugate gaze palsy, were commonly associated with pontine lesions, and dysphagia was common in medullary lesions. Ten out of 18 patents showed significant stenosis (≧50%) of the relevant vertebral artery. Two patients had aortic atheroma >4 mm, and 1 patient had atrial fibrillation. Conclusions: Clinical features of vertigo, contralateral falls and gaze-evoked nystagmus are suggestive of an NPH lesion. Accompanying signs of ipsilateral facial palsy of the peripheral type and/or horizontal gaze palsies are highly specific for a pontine NPH lesion. Large-artery atherosclerosis was the most common causative mechanism of infarctions involving the NPH area.
Intra-Arterial Thrombolytic Therapy for Hyperacute Ischemic Stroke Caused by Tandem Occlusion
Authors: Kim Dong Joon , Kim Dong Ik , Byun Joon Soo , Jung Jin Young , Suh Sang Hyun , Kim Eung Yeop , Heo Ji Hoe
Published: July 2008

Background: Tandem occlusion of the arteries at the extracranial and intracranial segments is a unique cause of ischemic stroke and is often associated with a poor prognosis. Although tandem occlusion is occasionally found during intra-arterial thrombolysis (IAT), as of yet no clear therapeutic strategy has been elucidated. Methods: After identifying distal intradural (DIL) and proximal extradural lesions (PEL) as well as the collateral state and clot burden, IAT was performed primarily targeting DIL by navigation of the microcatheter through the PEL or a collateral pathway. Results: Among 147 consecutive patients who were treated with IAT for hyperacute ischemic stroke, 13 (11.4%) were identified to have tandem occlusion as the cause of stroke. Navigation of a microcatheter through occluded PEL (internal carotid artery/vertebral artery) or a collateral pathway (anterior communicating artery) to the DIL was successful in 9 patients. Of them, recanalization of the DIL could be achieved in 8 (89%). The overall recanalization rate among all patients with tandem occlusion was (62%, 8/13). A good functional outcome (modified Rankin score ≤2) at 3 months was noted in 6 patients (46.2%). Conclusions: Tandem occlusion may be successfully managed by strategic thrombolysis of the DIL as the primary therapeutic target for IAT. By this strategy, the ischemic brain could be effectively and rapidly perfused.
The Positive Effect of Integrated Care on Depressive Symptoms in Stroke Survivors
Authors: Joubert Jacques , Joubert Lynette , Reid Chris , Barton David , Cumming Toby , Mitchell Peter , House Molly , Heng Robert , Meadows Graham , Walterfang Mark , Pantelis Christos , Ames David , Davis Stephen
Published: July 2008

Background: Depressive symptoms occur in approximately one-third of stroke patients. We sought to evaluate whether an integrated model of stroke care and secondary prevention reduced depressive symptomatology in stroke survivors. Methods: The integrated care (IC) model is a multifaceted program that provides ongoing collaboration between a specialist stroke service and primary care physicians, using telephone tracking, a bi-directional information feedback loop, management of vascular risk factors, and regular screening for depressive symptoms. Results: Patients exposed to the IC model exhibited significantly fewer depressive symptoms than controls at 12 months post stroke (as measured by the PHQ-9 screening tool; p = 0.006). At 12 months, 30/91 (33%) of the treatment group had depressive symptoms, compared to 52/95 (55%) of the control group (p = 0.003). With other variables adjusted for, the major associates of being depressed at 12 months were group allocation and physical disability. Conclusion: The integrated care approach provides a framework for detecting and monitoring depressive symptoms, and appears to be protective against post-stroke depression.
Corneal Hysteresis and Corneal Resistance Factor in Keratoectasia: Findings Using the Reichert Ocular Response Analyzer
Authors: Kirwan Caitriona , O’Malley Donal , O’Keefe Michael
Published: July 2008

Aim: To examine corneal hysteresis (CH) and corneal resistance factor (CRF) in normal and ectatic corneas. Methods: CH and CRF were measured using the Reichert Ocular Response Analyzer in patients with clinically diagnosed keratoconus (KC), forme fruste KC (FFKC) and normal eyes. Results: 21 eyes (13 patients) with clinically diagnosed KC and 30 eyes (18 patients) with FFKC were included in the study. Mean CH and CRF in FFKC did not differ from that in pachymetry-matched normal eyes. KC eyes had significantly lower CH and CRF than normal and FFKC eyes. Conclusion: A significant overlap in CH and CRF values among the 3 groups was evident. Our findings do not indicate a role for CH and CRF measurement as a single test to aid in the detection of early ectasia. It may be of use when used in conjunction with other parameters such as aberrometry. CH and CRF values may prove to be useful in monitoring ectasia progression.
Rat RFRP-3 Alters Hypothalamic GHRH Expression and Growth Hormone Secretion but Does Not Affect KiSS-1 Gene Expression or the Onset of Puberty in Male Rats
Authors: Johnson Marlie A. , Fraley Gregory S.
Published: July 2008

Background/Aims: RFRP-3 is a recently described neuropeptide that influences a variety of physiologic factors, including the inhibition of gonadotropin secretion and reproductive behaviors. We hypothesized that endogenous RFRP-3 could function to inhibit the onset of puberty in young male rats. Methods: To test this hypothesis, we first placed cannulas into the third ventricle of 24-day-old male rat pups. The cannulas were attached to osmotic minipumps that infused antisense oligonucleotides (ODNs) against RFRP-3. Second, cannulas were placed in the ventricle of 35-day-old pups and infused with RFRP-3, NPFF (putatively, an alternative transcript of the RFRP gene), or vehicle. Results: No treatment altered the onset of puberty compared to controls. RFRP-3 ODN rats had significantly larger testes compared to control rats. Similarly, the RFRP-3 ODN-treated rats had a significant increase in plasma LH, but not FSH, compared to control rats. Rats infused with RFRP-3 exhibited significantly smaller testes compared to control rats. RFRP-3 rats also had a significant decrease in plasma LH levels. RFRP-3 infusion elicited a significant increase in growth hormone-releasing hormone mRNA and plasma growth hormone levels compared to control rats. Neither peptide had an effect on KiSS-1 mRNA expression. Conclusion: These data suggest that endogenous rat RFRP-3 does not affect the timing of puberty in male rats but may be associated with peripubertal rise in growth hormone secretion.
The Influence of the Elderly on School Spending in a Median Voter Framework
Authors: Fletcher Deborah , Kenny Lawrence W.
Published: July 2008

How do the elderly influence school spending if they are a minority of the population? We estimate the determinants of school spending in a median voter model, comparing four assumptions about how the elderly influence the identity of the median voter. Using a county-level panel, we find that elderly preferences are best characterized by assuming all elderly or all elderly migrants vote with the poor. Having more elderly results in a median voter who is further down the community's income distribution. This median voter is poorer, which lowers preferred school spending, and faces a lower tax price, which raises preferred school spending. The evidence suggests that the income effect is slightly larger than the price effect, so the elderly on net cause a very small drop in spending. Thus the widespread concern about the negative impact of population aging on school funding seems to be misplaced.