Brain death (BD) is an important multifactorial variable contributing to donor-specific liver damage. Our study aimed at assessing the specific effects of hemodynamic instability on systemic and ...hepatic parameters of perfusion, bowel ischemia, and oxidative stress in a porcine model of BD.
BD was induced in 16 pigs (German Landrace, 18-28 kg) in two groups (hypotension-BD HYPO-BD, n=8; normotension-BD NORM-BD, n=8), which were compared with control animals/living donors (n=6) for a period of 2 hr. We analyzed systemic hemodynamic parameters, bowel ischemia (intramucosal pH in the stomach and colon, plasma endotoxin levels, and endotoxin-neutralizing capacity ENC), and oxidative stress (total glutathione levels in erythrocytes) and compared the findings with hepatic parameters of perfusion (hepatic arterial flow, portal venous flow, and microperfusion) and liver oxidative stress (reduced glutathione and oxidized glutathione levels in the liver).
Independent of the hemodynamic stability, liver macrocirculation and microcirculation decreased (HYPO-BD, 79+/-6 to 69+/-10 mL/100 g/min; NORM-BD, 81+/-10 to 73+/-7 mL/100 g/min; P<0.05). Hepatocellular damage (aspartate aminotransferase: NORM-BD, 49+/-20 units/L; HYPO-BD, 170+/-140 units/L; P<0.01) and hepatic oxidative stress (reduced glutathione in the liver/oxidized glutathione in the liver: NORM-BD, 29.4+/-2.3 to 13.0+/-1.3; HYPO-BD, 29.4+/-2.3 to 9.05+/-0.81; P<0.001) increased in both BD groups. With dependence on systemic hemodynamic parameters, bowel ischemia increased (intramucosal pH in the colon, 7.22+/-0.01, P<0.01; ENC, 75+/-14 endotoxin-neutralizing units/mL, P<0.01; endotoxin levels, 7+/-2 to 43+/-10 pg/mL, P<0.01) in the HYPO-BD group but not in the NORM-BD group or the living donor group. Furthermore, systemic oxidative stress was increased in the HYPO-BD group only (total glutathione levels in erythrocytes, 2.65+/-0.25 to 0.15+/-0.25 mM; P<0.01).
During BD, liver-specific parameters (portal venous flow, microperfusion, aspartate aminotransferase activity, ENC, and hepatic oxidative stress) were compromised, independent of the hemodynamic status. Therefore, the systemic hemodynamic status does not reflect the functional status of the liver during BD.
Total alpha-fetoprotein (AFP) concentrations and proportions of AFP non-reactive with the lectin concanavalin A (Con A) were studied in extracellular fluid of 22 first-trimester fetuses. Total AFP ...concentrations were significantly lower in fetuses with Down's syndrome than in those with Mendelian-inherited diseases and normal karyotypes. The proportion of non-Con-A-reactive AFP was low in the fetal compartment (< or = 3.5%) irrespective of the fetal karyotype. So the AFP production in the fetal liver as well as in the yolk sac seems to be reduced in Down's syndrome. The fetus itself contributes only marginally to the non-Con-A-reactive AFP pool of amniotic fluid, which is therefore almost entirely of yolk sac origin. This pool is preserved well into the second trimester of pregnancy, despite cessation of yolk sac AFP production at the end of the first trimester, indicating a very slow rate of disappearance of proteins out of amniotic fluid.
Elevated zinc serum concentrations have been shown to restore impaired immune response. Therefore, pharmacologic zinc supplementation has been used to improve immune function, particularly in ...intensive care patients. In these patients, Gramnegative sepsis, the symptoms of which are predominantly caused by LPS-induced release of monokines, represents a serious problem. We have recently shown that zinc enhances induction of TNF-alpha and IL-1 beta in cultures of PBMC by LPS. By fluorescence polarization and infrared spectroscopic measurements we found that zinc addition leads to decreased fluidity of the hydrocarbon chains of LPS. Experiments at different temperatures showed that the less fluid gel (beta) phase of LPS is more effective in cytokine induction than the more fluid liquid-crystalline (alpha) phase. Our studies suggest that the synergistic effect of zinc on monokine induction by LPS is caused by direct interaction of zinc with LPS altering the fluidity of the hydrocarbon chains. Although this effect is zinc specific, other divalent ions, like cobalt and nickel, with a complex structure and size comparable to those of zinc also enhance LPS-induced monokine secretion but to a much lesser extent. Our data indicate that the zinc level represents a relevant clinical parameter in the treatment of Gram-negative infection. This reveals potential risks in the therapeutic application of zinc.
To determine the effect of atracurium or pancuronium on onset and duration of fetal paralysis, movements and heart rate parameters directly after transfusion, using computer analyzed fetal heart rate ...recording (c-FHR).
Double blind randomized study of 23 RhD alloimmunized pregnant women requiring an intravascular intrauterine fetal blood transfusion (IUT) between 24 and 36 weeks. Atracurium was injected in 11 fetuses at 17 IUT's and pancuronium in 12 fetuses at 19 IUT's. For statistical analysis the Mann-Whitney test was used.
No statistical differences were found in fetal heart rate and movements between both groups before transfusion. The fetal movements returned more rapidly in the atracurium group when compared to the pancuronium-group (median 24 vs. 57 min, range 6-55 vs. 4-220; (p<0.02). Fetal movements did not hamper the procedure in any case. The atracurium group showed significantly more fetal movements (p<0.01), more accelerations (0<0.05) but no significant reduction of fetal heart rate variability directly after transfusion which was in direct contrast to the pancuronium group.
Neuromuscular blockade with atracurium produces sufficient paralysis for intrauterine transfusion with minimal disturbance of the parameters used to monitor fetal wellbeing after the procedure. Although the routine use of fetal paralysis during IUT may be questionable, we believe that when it is necessary the use of atracurium is the better choice.
In this paper we present a prototype of a mobile terminal which features the scalable extension of H.264/AVC namely SVC. Due to the fact that SVC uses most of the basic algorithms which can be found ...in H.264/AVC, we've analyzed how an existing H.264/AVC decoder can be used for SVC to build a complete terminal. This terminal will be used for an upcoming LTE field trial in Berlin / Germany promoting SVC as a video coding standard in a broadcast scenario.
Use of antiepileptic drugs (AEDs) during pregnancy is associated with an increased risk of congenital malformations. Spina bifida aperta has been linked specifically to valproic acid (VPA) (estimated ...risk, 1 to 2%). The actual risk, the exclusive association of VPA with spina bifida and not anencephaly, and the precise causative relation remain matters of discussion. A prospective cohort study of pregnant women with epilepsy receiving AEDs and referred for prenatal diagnosis before week 22 of gestation was conducted, with follow-up to 3 months after birth. Pregnancies (291 singleton and 6 twin) in 261 women were evaluated. The prevalence of anomalies after exposure to any AED was 6.9%. For fetuses exposed to VPA, the prevalence was 9.4%, including six cases of spina bifida, two of which were in monozygotic twins (giving a prevalence rate of 6.3%, or 5.4%, if twins counted as one). Spina bifida was associated with a significantly higher average daily dose of VPA as compared with pregnancies with normal outcome (1.640 +/- 136 mg/d vs 941 +/- 48 mg/d, p = 0.0001). No relation was observed between the occurrence of spina bifida and type of maternal seizure or epilepsy, family history of epilepsy or neural-tube defects, or medical history. From these results we suggest that when the use of VPA during pregnancy cannot be avoided, the teratogenic risk might be diminished by reduction of the daily dose.
Certain thyronine-insulin analogues, which form non-covalent complexes with plasma proteins, have been shown to act preferentially in the liver. We hypothesized that this property may be dependent on ...the ability of the analogue to bind to the insulin receptor without prior dissociation from the binding protein. NaB1-L-thyroxyl-insulin, NaB1-3,3',5'-triiodothyronine-insulin, NaB1-D-thyroxyl-insulin and NaB1-L-thyroxyl-aminolauroyl-insulin were compared with insulin for their capacity to inhibit the binding of 125ITyrA14-insulin to rat liver plasma membrane in albumin-free buffer. Effective doses at 50% maximum inhibition of binding (ED50) were calculated with and without addition of the thyroid hormone binding proteins transthyretin, thyroxine binding globulin and human serum albumin. The binding of thyronine-insulin analogues to insulin receptors was inhibited in a dose-dependent manner by the addition of thyroid hormone binding proteins at concentrations in the physiological range. Complexes of thyronine-insulin analogues with thyroid hormone binding proteins exhibit impaired insulin receptor binding affinities compared with those of the analogues in their free form. Hepatoselectivity in vivo may not depend on binding of the intact complexes to hepatocytes. These results have implications for the physiological role of hormone binding proteins and the in vivo properties of other insulin analogues which bind to plasma proteins.
The interaction of bacterial endotoxins lipopolysaccharide (LPS) and the ‘endotoxic principle’ lipid A, with high‐density lipoprotein (HDL) from serum was investigated with a variety of physical ...techniques and biological assays. HDL exhibited an increase in the gel to liquid crystalline phase transition temperature Tc and a rigidification of the acyl chains of the endotoxins as measured by Fourier‐transform infrared spectroscopy and differential scanning calorimetry. The functional groups of the endotoxins interacting with HDL are the phosphates and the diglucosamine backbone. The finding of phosphates as target groups is in accordance to measurements of the electrophoretic mobility showing that the zeta potential decreases from −50 to −60 mV to −20 mV at binding saturation. The importance of the sugar backbone as further target structure is in accordance with the remaining negative potential and competition experiments with polymyxin B (PMB) and phase transition data of the system PMB/dephosphorylated LPS. Furthermore, endotoxin binding to HDL influences the secondary structure of the latter manifesting in a change from a mixed α‐helical/β‐sheet structure to a predominantly α‐helical structure. The aggregate structure of the lipid A moiety of the endotoxins as determined by small‐angle X‐ray scattering shows a change of a unilamellar/inverted cubic into a multilamellar structure in the presence of HDL. Fluorescence resonance energy transfer data indicate an intercalation of pure HDL, and of LPS–HDL complexes into phospholipid liposomes. Furthermore, HDL may enhance the lipopolysaccharide‐binding protein‐induced intercalation of LPS into phospholipid liposomes. Parallel to these observations, the LPS‐induced cytokine production of human mononuclear cells and the reactivity in the Limulus test are strongly reduced by the addition of HDL. These data allow to develop a model of the endotoxin/HDL interaction.
A small-angle large-acceptance detection system for hadrons Kalantar-Nayestanaki, N.; Bacelar, J.C.S.; Brandenburg, S. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2000, Letnik:
444, Številka:
3
Journal Article
Recenzirano
The performance of a segmented large-acceptance detector, capable of measuring particles at small forward angles, is presented. The Small-Angle Large-Acceptance Detector (SALAD), was built to handle ...very high rates of particles impinging on the detector. Particles down to a few MeV can be detected with it. The position of charged particles is measured by two Multi-Wire Proportional Chambers while scintillator blocks are used to measure the energy of the detected particle. A stack of thin scintillators placed behind the energy detectors allows for a hardware rejection (veto) of high-energy particles going through the scintillator blocks.
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