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1.
Anaesthesist ; 69(9): 685-698, 2020 09.
Artigo em Alemão | MEDLINE | ID: mdl-32757033

RESUMO

The term anaphylaxis describes a severe, potentially life-threatening allergic reaction. It is caused by an acute, systemic immune response to substances against which in most cases a previous sensitization has taken place. An anaphylactic reaction can affect every organ system of the human body. The first signs of an allergic shock are symptoms such as hypotension, tachycardia, exanthema and dyspnea. The complete expression of anaphylactic shock can occur very quickly. A perioperative anaphylaxis, in particular, is not always easy to recognize. Therefore, it is important to know the possible perioperative triggers of anaphylaxis, for instance neuromuscular blocking agents and antibiotics. The treatment has to be initiated quickly to save the life of the patient. The rapid injection of epinephrine and intravenous fluid administration are most important.


Assuntos
Anafilaxia/fisiopatologia , Anafilaxia/terapia , Idoso , Anafilaxia/diagnóstico , Anafilaxia/tratamento farmacológico , Humanos , Masculino
2.
Clin Infect Dis ; 69(2): 268-277, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-30329017

RESUMO

BACKGROUND: Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS. METHODS: In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics. RESULTS: We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease. CONCLUSIONS: Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations.


Assuntos
Disbiose/complicações , Microbioma Gastrointestinal , Recém-Nascido Prematuro , Metaboloma , Sepse Neonatal/patologia , Anaerobiose , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Fezes/química , Fezes/microbiologia , Humanos , Lactente , Recém-Nascido , Masculino , Metabolômica , Metagenômica , Filogenia , Estudos Prospectivos , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
3.
Poult Sci ; 97(3): 920-929, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29300969

RESUMO

The objective of this study was to investigate the effects of supplementation with free myo-inositol (MI) or graded levels of phytase on inositol phosphate (InsP) degradation, concentrations of MI in the digestive tract and blood, bone mineralization, and prececal digestibility of amino acids (AA). Ross 308 broiler hatchlings were allocated to 40 pens with 11 birds each and assigned to one of 5 treatments. The birds were fed a starter diet until d 11 and a grower diet from d 11 to d 22. All diets were based on wheat, soybean meal, and corn. Birds were fed a control diet, calculated to contain adequate levels of all nutrients without (C) or with MI supplementation (C+MI), or one of 3 experimental diets that differed in phytase level (modified E. coli-derived 6-phytase; Phy500, Phy1500, or Phy3000 FTU/kg), with P and Ca levels adapted to the recommendations of the phytase supplier for a phytase level of 500 FTU/kg. The gain:feed ratio (G:F) was increased by MI or phytase in the starter+grower phase by 0.02 g/g. Prececal P and Ca digestibility, P and Ca concentration in blood serum, and tibia ash weight did not differ among treatments (P > 0.05). MI supplementation led to the highest MI concentration in the crop, ileum, and blood plasma across treatments. Phytase supplementation increased MI concentrations in the crop and ileum digesta in a dose-dependent manner and in plasma without any dose effect (P > 0.05). Prececal digestibility of some AA was increased by phytase. These outcomes indicate that MI might have been a relevant cause for the increase in G:F. Therefore, it is likely that the release of MI after complete dephosphorylation of phytate is one of the beneficial effects of phytase, along with the release of P and improvement in digestibility of other nutrients. Simultaneously, MI seems to have no diminishing effects on InsP degradation.


Assuntos
6-Fitase/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Galinhas/fisiologia , Digestão/efeitos dos fármacos , Fosfatos de Inositol/fisiologia , Inositol/metabolismo , 6-Fitase/administração & dosagem , Aminoácidos/fisiologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Cálcio/fisiologia , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Trato Gastrointestinal/fisiologia , Inositol/administração & dosagem , Inositol/sangue , Fósforo/fisiologia , Distribuição Aleatória
4.
Phys Rev E ; 94(2-1): 023203, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27627403

RESUMO

The collisional (or free-free) absorption of soft x rays in warm dense aluminium remains an unsolved problem. Competing descriptions of the process exist, two of which we compare to our experimental data here. One of these is based on a weak scattering model, another uses a corrected classical approach. These two models show distinctly different behaviors with temperature. Here we describe experimental evidence for the absorption of 26-eV photons in solid density warm aluminium (T_{e}≈1 eV). Radiative x-ray heating from palladium-coated CH foils was used to create the warm dense aluminium samples and a laser-driven high-harmonic beam from an argon gas jet provided the probe. The results indicate little or no change in absorption upon heating. This behavior is in agreement with the prediction of the corrected classical approach, although there is not agreement in absolute absorption value. Verifying the correct absorption mechanism is decisive in providing a better understanding of the complex behavior of the warm dense state.

5.
Opt Lett ; 40(13): 3205-8, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-26125403

RESUMO

We demonstrate a method of using a Fourier holographic technique to utilize attosecond soft x-ray pulses to image nanometer-scale objects. A discrete frequency comb of laser-generated high-order harmonics, yielding a train of attosecond pulses, has been used to record spatially and spectrally resolved images. The individual wavelengths were also combined to form a single image, albeit with lower spatial resolution, demonstrating the applicability of the method to using isolated attosecond pulses with continuous bandwidths.

6.
Appl Opt ; 54(15): 4745-9, 2015 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-26192510

RESUMO

We report on the shot-to-shot stability of intensity and spatial phase of high-harmonic generation (HHG). The intensity stability is measured for each high-harmonic (HH) order with a spectrometer. Additionally, the spatial phase is measured with an XUV wavefront sensor for a single HH order measured in a single shot, which according to our knowledge was not reported before with a Hartmann wavefront sensor. Furthermore, we compare the single-shot measurement of the spatial phase with time-integrated measurements and we show that the XUV wavefront sensor is a useful tool to simultaneously optimize the spatial phase and intensity of HHG within the available HHG parameter range used in this study.

7.
J Enzyme Inhib ; 16(3): 241-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11697044

RESUMO

Several new analogs of the known thrombin inhibitor NAPAP were synthesized, in which the P2 glycine residue was substituted by natural and unnatural amino acids. The thrombin inhibitory potency was comparable to that of NAPAP. Several of the compounds had inhibition constants lower than 10 nM and a very high selectivity compared to trypsin, factor Xa and plasmin. In addition, analogs were prepared by alkylation of the N alpha-atom of the 4-amidinophenylalanine in P1 position, which showed a more than 10-fold lower thrombin inhibition. Furthermore, azaglycine was introduced instead of P2 glycine. For most of the inhibitors similar fast elimination rates were seen in rats after intravenous dosing, as found previously for NAPAP. Only some compounds, which contained a second basic group showed a slightly decreased cumulative biliary clearance.


Assuntos
Antitrombinas/síntese química , Antitrombinas/metabolismo , Dipeptídeos/síntese química , Dipeptídeos/metabolismo , Piperidinas/síntese química , Piperidinas/metabolismo , Animais , Antitrombinas/química , Antitrombinas/isolamento & purificação , Antitrombinas/farmacocinética , Bile/química , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Dipeptídeos/farmacocinética , Feminino , Glicina/química , Glicina/metabolismo , Estrutura Molecular , Piperidinas/química , Piperidinas/isolamento & purificação , Piperidinas/farmacocinética , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Trombina/metabolismo , Fatores de Tempo
8.
Eur J Biochem ; 265(2): 598-605, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10504391

RESUMO

Two bivalent thrombin inhibitors were synthesized, which consist of a benzamidine-based active-site-blocking segment, a fibrinogen recognition exosite inhibitor and a peptidic linker connecting these fragments. BZA-1 hirulog contains an Nalpha-(2-naphthylsulfonyl)-S-3-amidinophenylalanyl-is onipecotic acid residue connected via the carboxyl group to the linker segment. The active-site-directed moiety of BZA-2 hirulog [Nalpha-(2-naphthylsulfonyl-glutamyl)-R-4-amidinophenylal anyl-piperid ide] was coupled to the linker via the side chain of the glutamic acid. Both BZA-hirulogs contain almost identical linker-exo site inhibitor parts, except for the substitution of a glycine as the first linker residue in BZA-1 hirulog by a gamma-amino butyric acid in BZA-2 hirulog, thus increasing flexibility and linker length by two additional atoms. BZA-1 hirulog showed moderate potency (Ki = 0. 50 +/- 0.14 nM), while BZA-2 hirulog was characterized as a slow, tight binding inhibitor of thrombin (Ki = 0.29 +/- 0.08 pM). The stability in human plasma of both analogs was strongly improved compared with hirulog-1. For BZA-2 hirulog a significantly reduced plasma clearance was observed after intravenous injection in rats compared with BZA-1 hirulog and hirulog-1. The X-ray structure of the BZA-2 hirulog in complex with human alpha-thrombin was solved and confirmed the expected bivalent binding mode.


Assuntos
Antitrombinas/química , Benzamidinas/química , Inibidores Enzimáticos/química , Guanidinas/química , Fenilalanina/análogos & derivados , Sequência de Aminoácidos , Animais , Sítios de Ligação , Cristalografia por Raios X , Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Cinética , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Molecular , Peptídeos/síntese química , Ratos
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