Application of ventricular tachyarrhythmia definitions of the updated Lambeth Conventions provides incompatibility with earlier results, masks antifibrillatory activity and reduces inter-observer agreement.

The Lambeth Conventions (LC I), a landmark guidance document for arrhythmia research was updated and arrhythmia definitions were changed in the new Lambeth Conventions II (LC II). This study examined whether the arrhythmia definitions of LC I and LC II yield the same qualitative results and whether LC II improves inter-observer agreement. Two independent investigators performed blinded arrhythmia analysis of the electrocardiograms of isolated, Langendorff rat hearts subjected to regional ischemia and perfused with Class I antiarrhythmics with 3 or 5 mM K+ in the perfusate. Data obtained with arrhythmia definitions of LC I and LC II were compared within and between observers. Applying ventricular fibrillation (VF) definition of LC II significantly increased VF incidence and reduced VF onset time irrespective of treatment by detecting 'de novo' VF episodes not found by LC I. LC II reduced the number of ventricular tachycardia (VT) episodes and simultaneously increased the number of VF episodes as compared with the respective values obtained according to LC I. Using VF definition of LC II masked the significant antifibrillatory effects of flecainide and the high K+ concentration identified with the VF definition of LC I. When VF incidence was tested, a very strong inter-observer agreement was found according to LC I, whereas using VF definition of LC II reduced inter-observer agreement. It is concluded that LC II shifts some tachyarrhythmias from VT to VF class, and thus results obtained by arrhythmia definitions of LC I and LC II are not compatible; VF definition of LC II may change the conclusion of pharmacological, physiological and pathophysiological arrhythmia investigations and may reduce inter-observer agreement. Thus, VT and VF definitions of LC II should be amended in order to increase compatibility and inter-observer agreement.

Hyperventilation assists proarrhythmia development during delayed repolarization in clofilium-treated, anaesthetized, mechanically ventilated rabbits.

Hyperventilation reduces partial pressure of CO2 (PCO2) in the blood, which results in hypokalaemia. Hypokalaemia helps the development of the life-threatening torsades de pointes type ventricular arrhythmia (TdP) evoked by repolarization delaying drugs. This implies that hyperventilation may assist the development of proarrhythmic events. Therefore, this study experimentally investigated the effect of hyperventilation on proarrhythmia development during delayed repolarization. Phenylephrine (an α1-adrenoceptor agonist) and clofilium (as a representative repolarization delaying agent inhibiting the rapid component of the delayed rectifier potassium current, IKr) were administered intravenously to pentobarbital-anaesthetized, mechanically ventilated, open chest rabbits. ECG was recorded, and the onset times and incidences of the arrhythmias were determined. Serum K+, pH and PCO2 were measured in arterial blood samples. Clofilium prolonged the rate corrected QT interval. TdP occurred in 15 animals (TdP+ group), and did not occur in 14 animals (TdP- group). We found a strong, positive, linear correlation between serum K+ and PCO2. There was no relationship between the occurrence of TdP and the baseline K+ and PCO2 values. However, a positive, linear correlation was found between the onset time of the first arrhythmias and the K+ and PCO2 values. The regression lines describing the relationship between PCO2 and onset time of first arrhythmias were parallel in the TdP+ and TdP- groups, but the same PCO2 resulted in earlier arrhythmia onset in the TdP+ group than in the TdP- group. We conclude that hyperventilation and hypocapnia with the resultant hypokalaemia assist the multifactorial process of proarrhythmia development during delayed repolarization. This implies that PCO2 and serum K+ should be controlled tightly during mechanical ventilation in experimental investigations and clinical settings when repolarization-delaying drugs are applied.

Full-genome sequencing of a Hungarian canine G3P[3] Rotavirus A strain reveals high genetic relatedness with a historic Italian human strain.

A canine Rotavirus A strain was identified in the fecal specimen of a young dog during 2012 in Hungary. The strain RVA/Dog-wt/HUN/135/2012/G3P[3] shared complete genotype constellation (G3-P[3]-I3-R3-C3-M3-A15-N2-T3-E3-H6) and high genome sequence similarity (nt, 98.8 %) with a historic human strain, RVA/Human-tc/ITA/PA260-97/1997/G3P[3]. This study provides evidence for the canine origin of the unusual NSP1 genotype, A15, and reinforces the hypothesis of direct interspecies transmission of canine rotaviruses to humans.

Monitoring of group A rotaviruses in wild-living birds in Hungary.

Rotavirus is a common pathogen causing gastroenteritis in humans and domesticated animals. The incidence of rotavirus in wild-living animals, particularly in avian species, has not been systematically investigated. In this study 1220 fecal samples and cloacal swabs collected from wild-living birds during 2008 in Hungary were tested for the presence of group A rotaviruses by a VP6 gene-specific reverse-transcription-polymerase-chain-reaction assay. Of the 1220 samples, 276 and 944 were processed as individual and pooled specimens, respectively. Rotavirus was identified in two pooled pheasant (Phasianus colchicus) samples and two individual reed bunting samples (Emberiza schoeniclus). These data indicated a very low prevalence of group A rotaviruses (0.3%) in our sample set. Nonetheless, the present study, together with existing literature data, implies that rotavirus infections occur in a wide spectrum of feral bird species. These findings are exciting and suggest that pursuing rotavirus monitoring is needed to uncover avian rotavirus strain diversity and understand rotavirus ecology in nature.

Activation and isomerization of n-butane on sulfated zirconia model systems--an integrated study across the materials and pressure gaps.

Butane activation has been studied using three types of sulfated zirconia materials, single crystalline epitaxial films, nanocrystalline films, and powders. A surface phase diagram of zirconia in interaction with SO(3) and water was established by DFT calculations, which was verified by LEED investigations on single-crystalline films and by IR spectroscopy on powders. At high sulfate surface densities a pyrosulfate species is the prevailing structure in the dehydrated state; if such species are absent, the materials are inactive. Theory and experiment show that the pyrosulfate can react with butane to give butene, H(2)O and SO(2), hence butane can be activated via oxidative dehydrogenation. This reaction occurred on all investigated materials; however, isomerization could only be proven for powders. Transient and equilibrium adsorption measurements in a wide pressure and temperature range (isobars measured via UPS on nanocrystalline films, microcalorimetry and temporal analysis of products measurements on powders) show weak and reversible interaction of butane with a majority of sites but reactive interaction with <5 micromol g(-1) sites. Consistently, the catalysts could be poisoned by adding sodium to the surface in a ratio S/Na = 35. Future research will have to clarify what distinguishes these few sites.

Abnormal cell-specific expressions of certain protein kinase C isoenzymes in peripheral mononuclear cells of patients with systemic lupus erythematosus: effect of corticosteroid application.

We have studied the expressions of various protein kinase C (PKC) isoenzymes in T cells and monocytes from patients with systemic lupus erythematosus (SLE), in comparison to those of healthy controls and patients with other immunological disorders. As measured by Western blotting, the levels of PKCbeta, delta, eta, epsilon, theta and zeta (but not of PKCalpha) significantly decreased in T cells of SLE patients. In monocytes, however, we observed marked suppressions only in the expressions of PKCdelta, epsilon and zeta but not in the expressions of other PKC isoforms. In vivo corticosteroid application, as well as in vitro steroid treatment of monocytes, elevated the expressions of most isoforms close to normal values; however, the decreased levels of PKCtheta and zeta were not affected by steroid application. These alterations were characteristic to SLE because we could not detect any changes in the PKC levels in mononuclear cells of primary Sjögren's syndrome and mixed connective tissue disease patients. These results suggest that impaired PKC isoenzyme pattern may exist in the T cells and monocytes of SLE patients. Furthermore, the clinically efficient glucocorticoid application in SLE can increase the expression of some members of PKC system.

Opposite roles of protein kinase C isoforms in proliferation, differentiation, apoptosis, and tumorigenicity of human HaCaT keratinocytes.

We have previously shown that the protein kinase C (PKC) system plays a pivotal role in regulation of proliferation and differentiation of the human keratinocyte line HaCaT which is often used to assess processes of immortalization, transformation, and tumorigenesis in human skin. In this paper, using pharmacological and molecular biology approaches, we investigated the isoform-specific roles of certain PKC isoenzymes (conventional cPKCalpha and beta; novel nPKCdelta and epsilon) in the regulation of various keratinocyte functions. cPKCalpha and nPKCdelta stimulated cellular differentiation and increased susceptibility of cells to actions of inducers of apoptosis, and they markedly inhibited cellular proliferation and tumor growth in immunodeficient mice. In marked contrast, cPKCbeta and nPKCepsilon increased both in vitro and in vivo growth of cells and inhibited differentiation and apoptosis. Our data present clear evidence for the specific, antagonistic roles of certain cPKC and nPKC isoforms in regulating the above processes in human HaCaT keratinocytes.

Presenilin-1 and the amyloid precursor protein are transported bidirectionally in the sciatic nerve of adult rat.

The amyloid precursor protein (APP) and presenilin-1 (PS-1) are not only of importance for the normal functioning of the various neurons, but also play central roles in the pathogenesis of Alzheimer's disease (AD). Through the use of immunohistochemical and Western blot techniques, the bidirectional axonal transport of these proteins has been demonstrated in the sciatic nerve of adult rat. Double-ligation of the sciatic nerve for 6, 12 or 24h was observed to cause a progressive accumulation of the 45kDa presenilin-1 holoprotein and APPs with molecular masses of 116 and 94kDa on both sites of the ligature. It is concluded that the functions of presenilin-1 and APPs are not restricted to the neuronal perikarya: they may carry information in both directions, from the cell body to the axon terminals and vice versa.

Phorbol ester treatment inhibits proliferation and differentiation of cultured human skeletal muscle satellite cells by differentially acting on protein kinase C isoforms.

We have previously shown that cultured human skeletal muscle cells express five protein kinase C (PKC) isoforms (PKCalpha, -gamma, -eta, -theta, and -zeta) and that expression levels of various PKC isozymes differentially change during differentiation. In this study we investigated the effects of the PKC activator phorbol 12-myristate 13-acetate (PMA) on differentiation and on PKC isozymes of human skeletal muscle satellite cells. PMA inhibited the growth and fusion of cultured human myoblasts in a dose-dependent manner. In addition, prolonged treatment of cells with PMA suppressed the expression of the myogenic differentiation marker desmin showing similar dose-response characteristics. Furthermore, PMA also induced the intracellular translocation of PKCgamma, -eta, and -theta, whereas cellular localization of PKCalpha and -zeta were not altered. These changes in subcellular localization patterns were of great importance since only those PKC isoforms were translocated that possessed alterations in their expression levels during differentiation. Our findings, therefore, suggest that the PMA-induced inhibition of differentiation of human skeletal muscle cells is mediated by certain PKC isoforms. Moreover, these data strongly argue for differential and isozyme-specific roles of various PKC isoforms in these processes.

Presenilin-1 and its N-terminal and C-terminal fragments are transported in the sciatic nerve of rat.

The axonal transport of presenilin-1 was investigated in a spinal cord-sciatic nerve-neuromuscular junction model system in the rat. The technique of unilateral sciatic nerve ligation, using double ligatures, was combined with immunohistochemical staining and Western blotting to examine the axonal transport of the protein. Immunohistochemical studies involving the use of polyclonal antibodies for either the N-terminal or the C-terminal domain of presenilin-1 furnished evidence that both fragments may be present not only in the neuronal cell bodies, but also in the motoric and sensory axons and the motoric axon terminals at the neuromuscular junctions. After double ligation of the sciatic nerve for 6, 12 or 24 h, progressive immunostaining of presenilin-1 occurred above the upper ligature and to a lesser extent below the lower ligature. Double staining of the sciatic nerve for presenilin-1 and for amyloid precursor protein revealed overlapping immunoreactivity. Western blotting confirmed the accumulation of the approximately 20-kDa C-terminal and approximately 25-kDa N-terminal fragments and the full-length 45-kDa holoprotein of presenilin-1 both above and below the ligature. It is concluded that besides the larger amounts of C-terminal and N-terminal fragments, a smaller quantity of intact presenilin-1 may be present and conveyed bidirectionally in the sciatic nerve of the rat. These results lend further support to the suggestion that presenilin-1 may leave the trans-Golgi network and be found in the axons and axon terminals of the various neurons.

Effects of chronic metrifonate treatment on cholinergic enzymes and the blood-brain barrier.

After an acute (4 h) treatment with an irreversible cholinesterase inhibitor organophosphate, metrifonate (100 mg/kg i.p.), the activities of both acetyl- and butyrylcholinesterase were inhibited (66.0-70.7% of the control level) in the rat brain cortex and hippocampus. There were no significant changes in the acetyl- and butyrylcholinesterase activities in the olfactory bulb, or in the choline acetyltransferase activity in all three brain areas. After chronic (2 or 5 week) metrifonate treatment (100 mg/kg daily i.p.), the activities of both cholinesterases were substantially inhibited in the rat brain cortex and hippocampus (15.8-31.8% of the control levels), but there was no inhibition of the choline acetyltransferase activity. Moreover, chronic metrifonate treatment did not have any effect on the distribution of the acetylcholinesterase molecular forms. In vitro, metrifonate proved to be a more potent inhibitor of butyryl- than of acetylcholinesterase in both the cortex and the hippocampus. In the hippocampus, the butyrylcholinesterase activity was twice as sensitive to metrifonate inhibition as that in the cortex (IC50 values 0.22 and 0.46 microM, respectively). The effects of chronic (5 week) metrifonate treatment on the blood-brain barrier of the adult rat were examined. The damage to the blood-brain barrier was judged by the extravasation of Evans' blue dye in three brain regions: the cerebral cortex, the hippocampus, and the striatum. No extravasation of Evans' blue dye was found in the brain by fluorometric quantitation. These data indicate that chronic metrifonate treatment may increase the extracellular acetylcholine level via cholinesterase inhibition, but it does not have any effects on the blood-brain barrier. Therefore, it appears reasonable to hypothesize that cholinesterase activities do not play a role in the blood-brain barrier permeability.

Donepezil dose-dependently inhibits acetylcholinesterase activity in various areas and in the presynaptic cholinergic and the postsynaptic cholinoceptive enzyme-positive structures in the human and rat brain.

In the symptomatic treatment of mild to moderately severe dementia associated with Alzheimer's disease, donepezil (E2020) has been introduced for the inhibition of acetylcholinesterase activity in the human brain. However, there is no morphological evidence as to how this chemical agent affects the acetylcholinesterase-positive structures in the various areas of the human and the rat CNS. This study demonstrates by histochemical means that donepezil exerts a dose-dependent inhibitory effect in vitro on acetylcholinesterase activity. The most sensitive areas were the cortex and the hippocampal formation. Within the different layers of the cortex, the cholinoceptive acetylcholinesterase-positive postsynaptic pyramidal cell bodies were more sensitive than the presynaptic cholinergic axonal processes. In the cortex, the cell body staining was already abolished by even 2 x 10(-8)M donepezil, whereas the axonal staining could be eliminated only by at least 5 x 10(-8)M donepezil. In the hippocampus, the axonal acetylcholinesterase reaction end-product was eliminated by 5 x 10(-7)M donepezil. The most resistant region was the putamen, where the staining intensity was moderately reduced by 1 x 10(-6)M donepezil. In the rat brain, the postsynaptic cholinoceptive and presynaptic cholinergic structures were inhibited by nearly the same dose of donepezil as in the human brain. These histochemical results provide the first morphological evidence that, under in vitro circumstances, donepezil is not a general acetylcholinesterase inhibitor in the CNS, but rather selectively affects the different brain areas and, within these, the cholinoceptive and cholinergic structures. The acetylcholinesterase staining in the nerve fibers (innervating the intracerebral blood vessels of the human brain and the extracerebral blood vessels of the rat brain) and at the neuromuscular junction in the diaphragm and gastrocnemius muscle of rat, was also inhibited dose dependently by donepezil. It is concluded that donepezil may be a valuable tool with which to influence both the pre- and the postsynaptic acetylcholinesterase-positive structures in the human and rat central and peripheral nervous systems.

Montmorillonites Modified with Carbonaceous Deposits.

The mechanism of formation of carbonaceous deposits on montmorillonites was studied for systems prepared by sorption of polymers on pillared montmorillonites and subsequent carbonization. Temperature-programmed desorption of ammonia and X-ray photoelectron spectroscopy showed that polymer was attached to Al-OH acidic sites of smectite layers. Pillars were not influenced to a greater extent. Islands of carbonaceous material were formed, but the amount of deposited carbon depended strongly upon carbonization conditions. The hydrophylic and acidic properties of carbon-covered silica aluminas differed strongly from those of the starting material. Copyright 2000 Academic Press.

In vitro effects of metrifonate on neuronal amyloid precursor protein processing and protein kinase C level.

Alteration in the processing of the amyloid precursor protein (APP) is a central event in the formation of amyloid deposits in the brains of individuals with Alzheimer's disease (AD). It has been suggested that acetylcholinesterase (AChE) inhibitors, which promote the cholinergic function and consequently improve the cognitive deficits, may also exert a neuroprotective effect by activating normal APP processing. We now report that an irreversible AChE inhibitor (metrifonate) increase the cell-associated APP level in a basal forebrain neuronal culture and also elevate the amount of APP secreted into the medium. The alterations in APP processing were accompanied by increased protein kinase C (PKC) levels. The results suggest that AChE inhibitors modulate the metabolism of APP, possibly via their stimulatory effects on PKC. Since changes in the activity and level of PKC may be involved in the pathogenesis of AD, it is concluded that the beneficial effect of metrifonate in AD therapy may be due not only to the stimulatory cholinergic function, but also to its activating effect on PKC.

Human amyloid-beta1-42 applied in vivo inhibits the fast axonal transport of proteins in the sciatic nerve of rat.

Human amyloid-beta1-42 has been suggested to be a pathogenetic factor in Alzheimer's disease. The precise mechanism by which this peptide causes the degeneration of neurons in the affected brain is not yet fully understood. By using immunohistochemistry we explored the inhibitory effects of human amyloid-beta1-42 applied in vivo on the fast axonal transport of acetylcholinesterase, the amyloid precursor protein, the vesicular acetylcholine transporter and synaptophysin in the sciatic nerve of rat. Our findings provide evidence for the in vivo neurotoxic effect of human amyloid-beta peptide.

El síndrome de Marcus Gunn. (Mandíbula - parpadeo): presentación de un caso clínico / The Marcus Gunn syndrome. (Jaw winking): report of a clinical case

Poco se ha escrito en la literatura odontológica sobre el conocido síndrome Marcus Gunn llamado también mandíbula parpadeo. Sin embargo es relevante el conocimiento de las características clínicas de esta entidad donde hay una asociación de movimientos involuntarios de elevación del párpado, en sincronismo con la lateralidad de la mandíbula. Se presenta un caso de este síndrome donde se observó una blefaroptosis leve, en una niña de 7 años de edad, la cual fue evidenciado en una consulta odontológica. El conocimiento de la existencia de esta patología reviste gran importancia pues requiere de varios cuidados postoperatorios y su remisión a los especialistas adecuados. Con este artículo se pretende hacer un aporte en el reconocimiento de enfermedades que aunque no están relacionadas directamente con el odontólogo, este debe conocer para su correcto manejo

Hemiatrofia facial progresiva (síndrome de Parry-Romberg). Presentación de dos casos / Progressive facial hemiatrophy (Parry-Romberg syndrome). Report of two cases

Se hace una revisión de la literatura sobre la hemiatrofia facial progresiva (síndrome de Parry-Romberg). La descripción de las características clínicas y la posible asociación con otras patologías permite la comprensión de este síndrome considerado por algunos autores como un trastorno del desarrollo causado por defectos de la vascularidad de la zona, producto de alguna causa infecciosa o traumática. Su etiología no está bien determinada, pero sí su aspecto clínico, el cual se repite en todos los pacientes. El llamativo aspecto asimétrico aue presenta el paciente y su conducta progresiva, sumado a otras condiciones asociadas con la neuralgia del trigémino, permite un rápido reconocimiento de esta enfermedad y su pronta derivación a los especialistas adecuados. Se presentan dos casos de pacientes con estadios diferentes de esta enfermedad que acudieron al Servicio de Cirugía Bucal de la Facultad de Odontología de la UCV que brindan un aporte en el conocimiento de la misma

Síndrome de Apert (Acrocefalosindactilia): presentación de dos casos clínicos / Apert syndrome: report of two clinical cases

Este artículo relativo al reporte de dos casos con síndrome de Apert tiene como objetivo hacer un aporte al conocimiento de algunos síndromes de rara aparición, pero que pueden ser motivo de consulta para el odontólogo. Se hace una revisión de la literatura donde se determina que es una enfermedad con un componente genético importante y se corresponde con algunas otras que presentan deformidades craneofaciales, con las que hay que hacer diagnósticos diferenciales. Las características más importantes de este síndrome radican, en la fusión de algunos huesos del cráneo, manos y pies dándole al paciente aspecto característico. Su tratamiento entra en el orden multidisciplinario ya que son múltiples las deformidades a tratar, por lo que se requiere la participación de médicos, odontólogos, foniatras, sicólogos y trabajadores sociales para encarar esta enfermedad

Vulnerability of small GABAergic neurons to human beta-amyloid pentapeptide.

beta-Amyloid peptide (A beta), the principal component of senile plaques in Alzheimer's disease, has been found to be neurotoxic. The role of A beta in the deficits of the GABAergic system in patients with Alzheimer's disease is unclear. It has been suggested that the cytotoxic activity of A beta is localized to amino acid residues 25-35 of this peptide, which contains a total of 42 amino acid residues. We now report that the short amyloid peptide fragments corresponding to amino acids 31-35 (A beta 31-35) and 34-39 (A beta 34-39) are also toxic in vitro to the small GABAergic neuron population of basal forebrain cultures. Morphological changes were accompanied by an increased number of varicosities localized on the processes of the GABA-immunoreactive neurons and by the appearance of round cells without processes. The neurodegeneration was confirmed by means of scanning electron microscopy. Quantification of the morphological findings by image analysis demonstrated a size-related dependence of the degeneration of GABAergic neurons. The results suggest that fragments of A beta shorter than A beta 25-35 may exert cytotoxic action and demonstrate the toxicity of these A beta fragments in decreasing the number of small GABAergic neurons.