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1.
Nature ; 618(7964): 270-275, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37225995

RESUMO

The gravitational pressure in many astrophysical objects exceeds one gigabar (one billion atmospheres)1-3, creating extreme conditions where the distance between nuclei approaches the size of the K shell. This close proximity modifies these tightly bound states and, above a certain pressure, drives them into a delocalized state4. Both processes substantially affect the equation of state and radiation transport and, therefore, the structure and evolution of these objects. Still, our understanding of this transition is far from satisfactory and experimental data are sparse. Here we report on experiments that create and diagnose matter at pressures exceeding three gigabars at the National Ignition Facility5 where 184 laser beams imploded a beryllium shell. Bright X-ray flashes enable precision radiography and X-ray Thomson scattering that reveal both the macroscopic conditions and the microscopic states. The data show clear signs of quantum-degenerate electrons in states reaching 30 times compression, and a temperature of around two million kelvins. At the most extreme conditions, we observe strongly reduced elastic scattering, which mainly originates from K-shell electrons. We attribute this reduction to the onset of delocalization of the remaining K-shell electron. With this interpretation, the ion charge inferred from the scattering data agrees well with ab initio simulations, but it is significantly higher than widely used analytical models predict6.

2.
Klin Monbl Augenheilkd ; 231(9): 909-14, 2014 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-24788606

RESUMO

BACKGROUND: The introduction and approval of Ocriplasmin as an intravitreally applicable drug in the pharmocological treatment of vitreomacular traction represents a new therapeutic approach possibly avoiding vitreoretinal surgery. With our article we report our first experience wih Ocriplasmin in clinical practice. METHODS: The indication for intravitreal therapy with Ocriplasmin was provided for symptomatic VMT or macular hole with VMT in 20 patients since March 2013. Surgery was planned in cases with remaining symptoms. Before IVI we performed SD-OCT. Best visual acuity (BCVA) was evaluated preoperatively, 7 and 28 days after treatment and finally every month in 14 treated eyes. SD-OCT images were analysed before treatment and later on with every follow-up examination. In addition to functional and morphological changes we analysed all side effects. RESULTS: The mean BCVA at the beginning of treatment was 0.3 and 0.4 before injection. The indications for treatment were as follows: symptomatic VMT in 10 patients and 4 patients suffering from full thickness macular hole stage 2. In 3 patients spontaneous regression of VMT could be observed with increasing of vision from 0.3 to 0.5. In one patient his macular hole was closed and BCVA increased from 0.2 to 0.6 within 7 days. Two patients showed significant enlargement of their macular holes after 7 days and finally underwent surgery. A massive cystoid macular oedema occurred in one patient. No change in the SD-OCT image could be observed 28 days after treatment. The mean visual acuity improved to 0.6 during a follow-up period of 90 days. Photopsia and disturbing vitreous opacities up to 28 days post injection could be regarded as minor side effects. CONCLUSION: Our first clinical experience with intravitreous injection of Ocriplasmin were performed to confirm the presumed therapeutic effect in patients suffering from VMT. Small macular holes could frequently be closed. The possibility of special side effects must be taken in consideration just as the possibility of spanteous improvement before performing IVI with Ocriplasmin. Further prospective studies must be recommended to be right about Ocriplasmin injections.


Assuntos
Fibrinolisina/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Perfurações Retinianas/tratamento farmacológico , Perfurações Retinianas/patologia , Descolamento do Vítreo/tratamento farmacológico , Descolamento do Vítreo/patologia , Fibrinolíticos/administração & dosagem , Humanos , Injeções Intravítreas , Projetos Piloto , Perfurações Retinianas/complicações , Aderências Teciduais/complicações , Aderências Teciduais/tratamento farmacológico , Aderências Teciduais/patologia , Resultado do Tratamento , Descolamento do Vítreo/complicações
3.
PLoS One ; 19(6): e0301002, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38848328

RESUMO

The known diversity of European middle and late Miocene hominids has increased significantly during the last decades. Most of these great apes were frugivores in the broadest sense, ranging from soft fruit frugivores most like chimpanzees to hard/tough object feeders like orangutans, varying in size from larger than siamangs (over 17 kg) to larger than most chimpanzees (~60-70 kg). In contrast to the frequent sympatry of hominoids in the early-to-middle Miocene of Africa, in no European Miocene locality more than one hominid taxon has been identified. Here we describe the first case of hominid sympatry in Europe from the 11.62 Ma old Hammerschmiede HAM 5 level, best known from its excellent record of Danuvius guggenmosi. The new fossils are consistent in size with larger pliopithecoids but differ morphologically from any pliopithecoid and from Danuvius. They are also distinguished from early and middle Miocene apes, share affinities with late Miocene apes, and represent a small hitherto unknown late Miocene ape Buronius manfredschmidi. With an estimated body mass of about 10 kg it represents the smallest known hominid taxon. The relative enamel thickness of Buronius is thin and contrasts with Danuvius, whose enamel is twice as thick. The differences between Buronius and Danuvius in tooth and patellar morphology, enamel thickness and body mass are indicative of differing adaptations in each, permitting resource partitioning, in which Buronius was a more folivorous climber.


Assuntos
Fósseis , Hominidae , Animais , Fósseis/anatomia & histologia , Hominidae/anatomia & histologia , Alemanha
4.
Sci Rep ; 14(1): 14377, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909077

RESUMO

We present a formally exact and simulation-free approach for the normalization of X-ray Thomson scattering (XRTS) spectra based on the f-sum rule of the imaginary-time correlation function (ITCF). Our method works for any degree of collectivity, over a broad range of temperatures, and is applicable even in nonequilibrium situations. In addition to giving us model-free access to electronic correlations, this new approach opens up the intriguing possibility to extract a plethora of physical properties from the ITCF based on XRTS experiments.

5.
J Hum Evol ; 62(1): 138-45, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22153571

RESUMO

A hominid upper premolar was discovered in the Azmaka quarry, near Chirpan (Bulgaria). The associated fauna, especially the co-occurrence of Choerolophodon and Anancus among the proboscideans, and Cremohipparion matthewi and Hippotherium brachypus among the hipparions, constrains the age of the locality to the second half of the middle Turolian (ca. 7 Ma), making it the latest pre-human hominid of continental Europe and Asia Minor. The available morphological and metric data are more similar to those of Ouranopithecus from the Vallesian of Greece than to those of the early to middle Turolian hominids of Turkey and Georgia, but the time gap speaks against a direct phyletic link, and Turolian migration from the east cannot be rejected.


Assuntos
Dente Pré-Molar/anatomia & histologia , Hominidae/anatomia & histologia , Animais , Evolução Biológica , Europa (Continente) , Fósseis , Hominidae/genética
6.
J Fish Biol ; 81(7): 2235-54, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23252737

RESUMO

This study compares electrocommunication behaviour in groups of freely swimming weakly electric fishes of two species, Marcusenius altisambesi and Mormyrus rume. Animals emitted variable temporal sequences of stereotyped electric organ discharges (EOD) that served as communication signals. While the waveform of individual signals remained constant, the inter-discharge interval (IDI) patterns conveyed situation-specific information. Both species showed different types of group behaviour, e.g. they engaged in collective (group) foraging. The results show that in each species, during different behavioural conditions (resting, foraging and agonistic encounters), certain situation-specific IDI patterns occurred. In both species, neighbouring fishes swimming closely together interacted electrically by going in and out of synchronization episodes, i.e. periods of temporally correlated EOD production. These often resulted in echo responses between neighbours. During group foraging, fishes often signalled in a repetitive fixed order (fixed-order signalling). During foraging, EOD emission rates of M. altisambesi were higher and more regular than those of M. rume. The two species also differed in the quantity of group behaviours with M. altisambesi being more social than M. rume, which was reflected in the lack of specific agonistic IDI patterns, more fixed-order signalling and more communal resting behaviour in M. altisambesi.


Assuntos
Comunicação Animal , Peixe Elétrico/fisiologia , Eletricidade , Comportamento Social , Comportamento Agonístico/fisiologia , Animais , Comportamento Animal/fisiologia , Especificidade da Espécie
7.
Gene ; 394(1-2): 69-77, 2007 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-17391869

RESUMO

For the first time the complete mitochondrial genome was sequenced for a member of Lacertidae. Lacerta viridis viridis was sequenced in order to compare the phylogenetic relationships of this family to other reptilian lineages. Using the long-polymerase chain reaction (long PCR) we characterized a mitochondrial genome, 17,156 bp long showing a typical vertebrate pattern with 13 protein coding genes, 22 transfer RNAs (tRNA), two ribosomal RNAs (rRNA) and one major noncoding region. The noncoding region of L. v. viridis was characterized by a conspicuous 35 bp tandem repeat at its 5' terminus. A phylogenetic study including all currently available squamate mitochondrial sequences demonstrates the position of Lacertidae within a monophyletic squamate group. We obtained a narrow relationship of Lacertidae to Scincidae, Iguanidae, Varanidae, Anguidae, and Cordylidae. Although, the internal relationships within this group yielded only a weak resolution and low bootstrap support, the revealed relationships were more congruent with morphological studies than with recent molecular analyses.


Assuntos
Genes Mitocondriais , Lagartos/classificação , Lagartos/genética , Animais , Composição de Bases , Sequência de Bases , DNA Mitocondrial/química , DNA Mitocondrial/genética , Genoma , Filogenia , RNA Ribossômico/genética , RNA de Transferência/genética , Répteis/classificação , Répteis/genética
8.
Urologe A ; 56(6): 773-778, 2017 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-28451747

RESUMO

BACKGROUND: Published studies on community-acquired urinary tract infections (UTI) often do not link microbiological findings with clinical risk factors and patient data. MATERIALS AND METHODS: We retrospectively correlated clinical findings of all patients with UTI of a urological outpatient clinic with the respective microbiological analysis of their urine samples over 2 periods of time: (A: 2005-2006 and B: 2011-2012). Patients were stratified to the following risk groups: uncomplicated cystitis, diabetes mellitus type 2, nursing home resident, prostatitis/epidydimitis, permanent catheter. RESULTS: The incidence of Escherichia coli (p < 0.001) and proteus (p < 0.001) significantly decreased from period A to B, while enterococci (p = 0.003) and staphylococci (p < 0.001) significantly increased. Antibiotic sensitivity to fosfomycin (p < 0.001), doxycycline (p < 0.001), nitrofurantoin (p < 0.001), and nitroxoline increased (p < 0. 001) and sensitivity to amoxicillin (p < 0.001) and gentamicin decreased (p < 0.001). Patients with a permanent catheter had significantly poorer sensitivity rates (50% and less) for almost all antibiotics tested compared to the overall group. The risk of a UTI with 3MRGN or MRSA bacteria was significantly higher for catheter carriers and nursing home residents. CONCLUSIONS: Empiric antibiotic first-line therapy with nitrofurantoin and fosfomycin for uncomplicated community acquired UTIs are well indicated in conformity with guidelines. The accumulation of multiresistant pathogens in patients with a permanent bladder catheter requires restrictive use of any permanent catheter drainage.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/microbiologia , Infecções Comunitárias Adquiridas/epidemiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Infecções Bacterianas/microbiologia , Infecções Comunitárias Adquiridas/microbiologia , Resistência Microbiana a Medicamentos , Humanos , Prevalência , Fatores de Risco , Cateterismo Urinário/estatística & dados numéricos
9.
Cardiovasc Res ; 37(3): 756-64, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9659460

RESUMO

OBJECTIVES: L-arginine exerts anti-atherosclerotic effects in hypercholesterolaemic rabbits via modulating endogenous NO production. We investigated whether L-arginine inhibits thromboxane formation in vivo and platelet aggregation ex vivo in this animal model. METHODS: The urinary excretion rates of 2,3-dinor-6-keto-PGF1 alpha (major urinary metabolite of PGI2) and 2,3-dinor-TXB2 (major urinary metabolite of thromboxane A2) were used as indicators of platelet-endothelial cell interactions in vivo. Rabbits were fed 1% cholesterol (Cholesterol group, N = 8), 1% cholesterol plus 2.25% L-arginine (Cholesterol + L-arginine, N = 8), or normal rabbit chow (Control, N = 4) for 12 weeks. Urine samples were collected in weekly intervals. At the end of the study period platelet aggregation ex vivo and endothelium-dependent and -independent vascular function of isolated aortic rings in vitro was assessed. RESULTS: Urinary 2,3-dinor-TXB2 excretion significantly increased in the cholesterol group (p < 0.05), and endogenous NO formation (measured as urinary nitrate excretion) decreased (p < 0.05). Both parameters were significantly correlated with each other (R = 0.48, p < 0.01). L-arginine partly restored urinary nitrate excretion and significantly reduced TXA2 production to values even below those in the control group (p < 0.001). Urinary 2,3-dinor-6-keto-PGF1 alpha excretion increased in early hypercholesterolaemia and returned to control values in the second half of the study period. The early increase in urinary 2,3-dinor-6-keto-PGF1 alpha excretion was attenuated by L-arginine. Platelet aggregation was significantly enhanced in cholesterol-fed rabbits and attenuated by dietary L-arginine. L-arginine also improved the impaired endothelium-dependent relaxations to ADP, and normalized the vasoconstrictor effects of 5-HT in isolated aortic rings. CONCLUSIONS: Cholesterol-feeding enhances platelet aggregation and TXA2 formation, and stimulates platelet-endothelial cell interaction in rabbits. These effects are probably due to impaired NO elaboration, as indicated by decreased urinary nitrate excretion. Chronic dietary supplementation with L-arginine elevates systemic NO elaboration and significantly increases the PGI2/TXA2 ratio. It thus beneficially influences the homeostasis between vasodilator and vasoconstrictor prostanoids in vivo.


Assuntos
Arginina/administração & dosagem , Dieta , Hipercolesterolemia/metabolismo , Agregação Plaquetária , Tromboxano A2/biossíntese , Difosfato de Adenosina/farmacologia , Animais , Aorta , Arginina/sangue , Biomarcadores/urina , Creatinina/urina , Endotélio Vascular/efeitos dos fármacos , Epoprostenol/urina , Cromatografia Gasosa-Espectrometria de Massas , Hipercolesterolemia/sangue , Técnicas In Vitro , Masculino , Nitratos/urina , Nitroprussiato/farmacologia , Coelhos , Tromboxano B2/análogos & derivados , Tromboxano B2/urina , Vasodilatadores/farmacologia
10.
FEBS Lett ; 333(1-2): 193-6, 1993 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-8224162

RESUMO

The distinct ATP-dependent transporters for taurocholate, leukotriene C4, and daunorubicin, studied in rat liver canalicular membrane vesicles, are sensitive to inhibition by cyclosporin A and its non-immunosuppressive analog PSC 833. Ki values for cyclosporin A were 0.2, 3.4 and 1.5 microM for the transport of taurocholate, leukotriene C4, and daunorubicin, respectively. The corresponding Ki values for PSC 833 were 0.6, 29, and 0.3 microM. Both inhibitors were competitive with respect to the three substrates. The cyclosporins serve as new and potent tools to interfere with different potency with the distinct ATP-dependent export carriers in the hepatocyte canalicular membrane.


Assuntos
Canalículos Biliares/metabolismo , Transporte Biológico Ativo/efeitos dos fármacos , Proteínas de Transporte/antagonistas & inibidores , Ciclosporinas/farmacologia , Trifosfato de Adenosina/fisiologia , Animais , Proteínas de Transporte/metabolismo , Membrana Celular/metabolismo , Daunorrubicina/metabolismo , Técnicas In Vitro , Leucotrieno C4/metabolismo , Masculino , Ratos , Ratos Wistar , Ácido Taurocólico/metabolismo
11.
Atherosclerosis ; 141(1): 31-43, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9863536

RESUMO

Vascular oxidative stress brought about by superoxide radicals and oxidized low-density lipoproteins (oxLDL) is a major factor contributing to decreased NO-dependent vasodilator function in hypercholesterolemia and atherosclerosis. We investigated whether chronic administration of L-arginine (2% in drinking water) or of alpha-tocopherol (300 mg/day) improves endothelium-dependent vasodilator function and systemic NO production, reduces vascular oxidative stress, and reduces the progression of atherosclerosis in cholesterol-fed rabbits with pre-existing hypercholesterolemia. Systemic NO production was assessed as urinary nitrate excretion; oxidative stress was measured by urinary 8-iso-PGF2alpha excretion in vivo, by lucigenin-enhanced chemiluminescence of isolated aortic rings ex vivo, and by copper-mediated LDL oxidation in vitro. Endothelium-dependent relaxation was almost completely abrogated in cholesterol-fed rabbits. Urinary nitrate excretion was reduced by 46+/-10%, and 8-iso-PGF2alpha excretion was increased by 61+/-18% as compared to controls (each P <0.05). Vascular superoxide radical release stimulated by PMA ex vivo was increased by 273+/-93% in this group, and the lag time of LDL oxidation was reduced by 35+/-6% (each P <0.05). Treatment with L-arginine and alpha-tocopherol reduced intimal lesion formation (by 68+/-6 and 4+/-11%, respectively; P <0.05) and improved endothelium-dependent relaxation. Both treatments also normalized urinary 8-iso-PGF2alpha excretion. L-Arginine increased urinary nitrate excretion by 43+/-13% (P <0.05) and reduced superoxide radical release by isolated aortic rings to control levels, which was unaffected by vitamin E treatment. By contrast, vitamin E dramatically increased the resistance of isolated LDL to copper-mediated oxidation in vitro by 178+/-7% (P <0.05), which was only marginally prolonged by L-arginine. Intimal thickening was reduced by both treatments. We conclude that both L-arginine and alpha-tocopherol reduce the progression of atherosclerotic plaques in cholesterol-fed rabbits. However, while L-arginine increases NO formation and reduces superoxide release, alpha-tocopherol antagonizes mainly oxLDL-related events in atherogenesis. Thus, both treatments reduce urinary isoprostane excretion and improve endothelium-dependent vasodilation via different mechanisms.


Assuntos
Aorta/fisiopatologia , Arginina/farmacologia , Endotélio Vascular/fisiopatologia , Hipercolesterolemia/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Aorta/metabolismo , Aorta/patologia , Arginina/administração & dosagem , Artérias Carótidas/patologia , Dieta , Dinoprosta/análogos & derivados , Dinoprosta/urina , F2-Isoprostanos , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Técnicas In Vitro , Lipoproteínas LDL/metabolismo , Medições Luminescentes , Masculino , Nitratos/urina , Óxido Nítrico/biossíntese , Oxirredução , Coelhos , Superóxidos/metabolismo , Vasodilatação , Vitamina E/administração & dosagem
12.
Biochem Pharmacol ; 48(6): 1113-20, 1994 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-7945404

RESUMO

Amphiphilic carboxylates acting as peroxisome proliferators and hypolipidemic drugs induce enzymes of peroxisomal lipid beta-oxidation, certain drug-metabolizing enzymes in the liver, and a number of additional proteins. The peroxisome proliferators represent a well-established class of non-genotoxic hepatocarcinogens. In this study we characterized the hepatic elimination of the peroxisome proliferator nafenopin. In the rat in vivo, 1 hr after intravenous administration of [3H]nafenopin, approx. 40% of injected radioactivity was recovered in bile. HPLC analysis of bile samples revealed that only about 10% of the radioactivity recovered in bile was associated with non-metabolized nafenopin and approx. 90% with more polar metabolites. One of the main metabolites formed in the liver and excreted into bile was identified as nafenopin glucuronide by beta-glucuronidase-catalysed reconversion to nafenopin. In mutant rats deficient in the canalicular transport of leukotriene C4 and related amphiphilic anion conjugates, recovery of [3H]nafenopin-derived radioactivity in bile was reduced to 4% of the injected dose. Although nafenopin glucuronide could not be detected in bile, it was a major metabolite in the liver from these mutant rats. Using membrane vesicles enriched in bile canalicular membranes from normal rats, transport of nafenopin glucuronide was shown to be a primary-active ATP-dependent process which was inhibited by leukotriene C4 and S-dinitrophenyl glutathione with IC50 values of 0.2 and 12 microM, respectively. ATP-dependent transport was not detectable for non-conjugated nafenopin. In canalicular membrane vesicles prepared from the mutant rats, the rate of ATP-dependent transport of nafenopin glucuronide was less than 10% of the transport observed in vesicles from normal rats. These data indicate that conjugation and subsequent transport by the ATP-dependent export carrier for leukotriene C4 and related conjugates is a major pathway for the elimination of nafenopin and structurally-related peroxisome proliferators.


Assuntos
Canalículos Biliares/metabolismo , Fígado/metabolismo , Nafenopina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Bile/metabolismo , Canalículos Biliares/ultraestrutura , Transporte Biológico , Glucuronatos/metabolismo , Masculino , Mutação , Ratos , Ratos Wistar , Trítio
13.
Microsc Res Tech ; 63(4): 220-43, 2004 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-14988920

RESUMO

The field of quantitative analysis and subsequent mapping of the cerebral cortex has developed rapidly. New powerful tools have been applied to investigate large regions of complex folded gyrencephalic cortices in order to detect structural transition regions that might partition different cortical fields of disjunct neuronal functions. We have developed a new mapping approach based on axoarchitectonics, a method of cortical visualization that previously has been used only indirectly with regard to myeloarchitectonics. Myeloarchitectonic visualization has the disadvantage of producing strong agglomerative effects of closely neighbored nerve fibers. Therefore, single and neurofunctional-relevant parameters such as axonal branchings, axon areas, and axon numbers have not been determinable with satisfying precision. As a result, different staining techniques had to be explored in order to achieve a suitable histologic staining for axon visualization. The best results were obtained after modifying the Naoumenko-Feigin staining for axons. From these contrast-rich stained histologic sections, videomicroscopic digital image tiles were generated and analyzed using a new fiber analysis framework. Finally, the analysis of histologic images provided topologic ordered parameters of axons that were transferred into parameter maps. The axon parameter maps were analyzed further via a recently developed traverse generating algorithm that calculated test lines oriented perpendicular to the cortical surface and white matter border. The gray value coded parameters of the parameter maps were then transferred into profile arrays. These profile arrays were statistically analyzed by a reliable excess mass approach we recently developed. We found that specific axonal parameters are preferentially distributed throughout granular and agranular types of cortex. Furthermore, our new procedure detected transition regions originally defined by changes of cytoarchitectonic layering. Statistically significant inhomogeneities of the distribution of certain axon quantities were shown to indicate a subparcellation of areas 4 and 6. The quantification techniques established here for the analysis of spatial axon distributions within larger regions of the cerebral cortex are suitable to detect inhomogeneities of laminar axon patterns. Hence, these techniques can be recommended for systematic and observer-supported cortical area mapping and parcellation studies.


Assuntos
Encéfalo/anatomia & histologia , Fibras Nervosas/ultraestrutura , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Humanos , Processamento de Imagem Assistida por Computador
14.
Adv Enzyme Regul ; 34: 371-80, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7942282

RESUMO

Cyclosporins are potent tools to inhibit several primary-active, ATP-dependent export carriers. This has been demonstrated in membrane vesicle transport assays for CsA and for its non-immunosuppressive analog PSC 833. Inhibition in the low micromolar and in the nanomolar concentration range is shown for the three distinct ATP-dependent export carriers in the liver canalicular membrane mediating the secretion into bile of leukotrienes (LTC4, other cysteinyl leukotrienes, and related conjugates), bile salts (taurocholate), and amphiphilic, mostly cationic substances (daunorubicin and other P-glycoprotein substrates). Competitive inhibition by cyclosporins is most potent for ATP-dependent taurocholate transport with Ki values of 0.2 and 0.6 microM for CsA and PSC 833, respectively. This inhibition is in agreement with in vivo studies in the rat demonstrating a block at the canalicular membrane in the hepatobiliary elimination of labeled taurocholate. The data suggest that cholestasis, as a side effect during CsA therapy, is largely due to inhibition of the ATP-dependent bile salt export carrier in the canalicular membrane. Inhibition by cyclosporins is less effective with respect to ATP-dependent leukotriene transport, both during biosynthetic release from mastocytoma cells and during hepatobiliary excretion. The Ki values for the former were 4.5 and 30 microM, and the Km/Ki ratios only 0.015 and 0.002 for CsA and PSC 833, respectively. Distinct transporters are inhibited by the cyclosporins with different potency and structurally modified cyclosporins may serve to induce preferential inhibition of a selected transporter. This is illustrated by the inhibition of the multidrug export carrier with daunorubicin as substrate using PSC 833 as inhibitor with a Ki value of 0.3 microM in an in vitro membrane transport system.


Assuntos
Trifosfato de Adenosina/metabolismo , Canalículos Biliares/metabolismo , Proteínas de Transporte/metabolismo , Membrana Celular/metabolismo , Ciclosporinas/farmacologia , Animais , Bile/metabolismo , Canalículos Biliares/citologia , Transporte Biológico Ativo/efeitos dos fármacos , Proteínas de Transporte/efeitos dos fármacos , Ciclosporina/farmacologia , Ciclosporinas/uso terapêutico , Daunorrubicina/metabolismo , Resistência a Múltiplos Medicamentos/fisiologia , Terapia de Imunossupressão/efeitos adversos , Leucotrieno C4/metabolismo , Masculino , Ratos , Ratos Wistar , Ácido Taurocólico/metabolismo
15.
J Chromatogr A ; 885(1-2): 351-9, 2000 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-10941682

RESUMO

Whole body synthesis of thromboxane A2 is best assessed by quantifying non-invasively its major urinary metabolite, i.e., 2,3-dinor-thromboxane B2 (2,3-dn-TxB2), by gas chromatography-mass spectrometry (GC-MS) or GC-tandem MS. Methods based on these techniques usually require a series of extraction and purification procedures including solid-phase extraction (SPE) and thin-layer chromatography (TLC) or liquid chromatographic separation of authentic or derivatized 2,3-dn-TxB2. Taking advantage of the inherent accuracy of GC-tandem MS and the high selectivity of the extraction of methoximated 2,3-dn-TxB2 on phenylboronic acid SPE cartridges we developed a method that involves only SPE steps prior to quantification by GC-tandem MS. The method was validated by performing in parallel an additional TLC step. Method mean accuracy and precision were of the order of 103% and 95%, respectively. The method allows furthermore co-processing of the same urine sample to quantify accurately and rapidly the major urinary metabolite of prostacyclin, i.e., 2,3-dn-6-oxo-prostaglandin (PG) F1 alpha, by GC-tandem MS. The limit of detection of the method was below each 5 pg of 2,3-dn-TxB2 and 2,3-dn-6-oxo-PGF1 alpha per 5 ml of urine. Our study suggests that dinor metabolites of isothromboxanes and isoprostacyclins are not abundantly present in human urine.


Assuntos
6-Cetoprostaglandina F1 alfa/análogos & derivados , Cromatografia em Camada Fina/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Tromboxano B2/análogos & derivados , 6-Cetoprostaglandina F1 alfa/urina , Humanos , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tromboxano B2/urina
16.
Lakartidningen ; 95(48): 5507-10, 5512-4, 1998 Nov 25.
Artigo em Sueco | MEDLINE | ID: mdl-9854378

RESUMO

The past twenty years have witnessed an increasing incidence of atopic dermatitis in Western Europe. The article consists in a discussion of the pathogenesis, clinical signs and treatment of this common skin disease. Both an IgE-mediated reaction on epidermal Langerhans cells, and a physiological/biochemical defect of the skin barrier structure may be crucial factors of the multifactorial pathogenesis. Local treatment with corticosteroids and moisturisers remains the basic approach, though the development of new more specific treatments is under way. Although much remains to be learned about atopic dermatitis, today all patients can be offered effective treatment resulting in improved quality of life.


Assuntos
Dermatite Atópica/epidemiologia , Adulto , Alérgenos/efeitos adversos , Criança , Dermatite Atópica/diagnóstico , Dermatite Atópica/etiologia , Dermatite Atópica/terapia , Feminino , Humanos , Lactente , Masculino , Educação de Pacientes como Assunto , Pele/patologia , Suécia/epidemiologia
17.
Eur J Clin Nutr ; 65(1): 77-80, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20823899

RESUMO

BACKGROUND: Studies suggest that honey has less influence on serum glucose concentrations than monosaccharides and disaccharides. Previous studies, however, have only analysed glucose metabolism. METHODS: This study investigated the influence of two types of honey (rapeseed and acacia) on the serum levels of glucose, fructose, insulin and C-peptide values in healthy subjects. The results were compared with honey-comparable glucose-fructose solutions. All solutions contained 75 g of glucose and/or fructose. RESULTS: We found significantly higher fructose serum levels with rapeseed honey after 2 h but no such differences for acacia honey. C-peptide levels were significantly higher after administration of both honeys after 1 and 2 h. CONCLUSIONS: For the first time it has been found out that honey ingestion leads to a rise of blood fructose concentration: in one case, this rise was lower than that achieved after fructose/glucose controls, in the other cases it was same as after the controls. Fructose metabolism may be inhibited by unidentified substances present in the rapeseed honey. Further study to elucidate underlying mechanisms may be worthwhile, as usually there is no differentiation between the different types of honey.


Assuntos
Glicemia/análise , Brassica rapa/química , Frutose/sangue , Mel , Acacia/química , Adulto , Peptídeo C/sangue , Carboidratos da Dieta , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Masculino , Adulto Jovem
19.
Neuroimage ; 16(4): 1103-19, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12202097

RESUMO

Quantitative analysis of the cerebral cortex has become more important since neuroimaging methods have revealed many subfunctions of cortical regions that were thought to be typical for only one specific function. Furthermore, it is often unknown if a certain area may be subdivided observer independently into subareas. These questions lead to an analytical problem. How can we analyze the cytoarchitecture of the human cerebral cortex in a quantitative manner in order to confirm classical transition regions between distinct areas and to detect new ones. Scanning the cerebral cortex is difficult because it presents a richly curved course and sectioning always leads to partially nonperpendicular sectioned regions of the tissue. Therefore, different methods were tested to determine which of them are most reliable with respect to generating perpendicular testlines in the cerebral cortex. We introduce a new technique based on electrical field theory. The results of this technique are compared with those of conventional techniques. It was found that straight traverses generated by the electrodynamic model present significantly smaller intertraversal differences than the conventional approaches.


Assuntos
Córtex Cerebral/citologia , Idoso , Algoritmos , Mapeamento Encefálico , Córtex Cerebral/fisiologia , Eletrofisiologia , Humanos , Masculino , Modelos Neurológicos
20.
Zentralbl Gynakol ; 111(18): 1205-14, 1989.
Artigo em Alemão | MEDLINE | ID: mdl-2531519

RESUMO

The T cell subpopulations in normal human endometrium were investigated by the immunoperoxidase technique with monoclonal antibodies. The total number of 100 endometrial biopsies from different phases of menstrual cycle were analyzed. It could be established, that the number of T cells shows typical variations during the cycle. The T suppressor cells increase in the ovulation and late luteal phase and decrease in the early luteal phase. The T helper cells were rare and without typical changes. It is assumed, that the regulation of T cells in the endometrium is connected with the formation of an optimal environment for the immigration of sperms and the implantation of the blastocyst.


Assuntos
Endométrio/imunologia , Linfócitos T/imunologia , Adulto , Anticorpos Monoclonais , Feminino , Humanos , Técnicas Imunoenzimáticas , Contagem de Leucócitos , Ciclo Menstrual , Pessoa de Meia-Idade , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia
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