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11.
Philipp Schlatter Heike Gutmann Juergen Drewe 《European journal of pharmaceutical sciences》2006,28(1-2):141-154
BACKGROUND: Kidney proximal tubular cells play a major role in the transport of endogenous and exogenous compounds. A multitude of different transporters are expressed starting with multidrug ABC transporters (e.g. abcb1, abcc1-6), slc22a6-8 (organic anion transporters) and slc22a1-3 (organic cation transporters). For transport studies of renal drug transport, cell lines like MDCK and LLC-PK1 are often used to overexpress and study one or two transporters, such as abcb1 or abcc1-6. However, the use is limited since under physiological conditions xenobiotics are transported through different transporters at the same time. Therefore, a primary in vitro model expressing functionally different transporters simultaneously, as it is the case in vivo, would be of great benefit. METHODS: Primary proximal tubular cells were isolated from porcine kidney. Cells were cultured under selective culturing conditions leading to specific growth of primary proximal tubular cells. Expression of important proximal transporters was checked at mRNA level with RT-PCR, at protein level with immunocytochemistry and functionally by transport and uptake assays. RESULTS: A model of primary proximal tubular cells was established expressing the most important transporters: abcb1, abcc1, abcc2, slc22a8, slco1a2, slc15a1, slc5a2 and slc4a4. In freshly isolated cells, slc22a1 and slc22a6 were expressed, but were down-regulated in culture. Abcb1, abcc1, abcc2 and slc4a4 were detected at protein level with immunostaining. Functional activity was confirmed for abcb1, abcc1/2, slc22a8, slc15a1/2 and slc5a1/2. The tightness of the monolayers of this model was better than in previously established in vitro models. CONCLUSION: This primary cell culture model might be an interesting tool to investigate proximal tubular transport and to predict toxicity and drug interactions since it expresses functionally several transporters simultaneously. 相似文献
12.
13.
S Schlegel W Maier M Philipp J B Aldenhoff I Heuser K Kretzschmar O Benkert 《Psychiatry research》1989,29(2):221-230
The relationship between psychopathology and brain alterations, measured by computed tomography (CT), was investigated in 44 depressed patients. Comparisons of ventricle-brain ratio (VBR) between "endogenous" vs. "nonendogenous" subgroups, classified by six distinct diagnostic systems, revealed no significant differences. The VBR and the width of the third ventricle correlated significantly with scores on the Brief Psychiatric Rating Scale, the Global Assessment Scale, the Bech-Rafaelsen Melancholia Scale, the Rating for Emotional Blunting, and the Scale for the Assessment of Negative Symptoms, but not with scores on the Hamilton Rating Scale for Depression and the Hamilton Rating Scale for Anxiety. Item analyses of the Bech-Rafaelsen Melancholia Scale revealed that retardation-related items were most significantly correlated with ventricular size. The wider diameter of the third ventricle in psychotic patients was associated with higher scores on retardation in the psychotic subgroup, whereas the greater distances of both Sylvian fissures showed no relationship to psychomotor retardation. No significant correlations were found between CT values and anxiety, suicidal impulses, somatic complaints, and sleep disturbances. 相似文献
14.
Mario T. Philipp Gary P. Wormser Adriana R. Marques Susan Bittker Dale S. Martin John Nowakowski Leonard G. Dally 《Clinical and Vaccine Immunology : CVI》2005,12(9):1069-1074
C6, a Borrelia burgdorferi-derived peptide, is used as the antigen in the C6-Lyme disease diagnostic test. We assessed retrospectively whether a fourfold decrease or a decrease to a negative value in anti-C6 antibody titer is positively correlated with a positive response to treatment in a sample of culture-confirmed patients with either early localized (single erythema migrans [EM]; n = 93) or early disseminated (multiple EM; n = 27) disease. All of these patients had been treated with antibiotics and were free of disease within 6 to 12 months of follow-up. Results show that a serum specimen taken at this time was either C6 negative or had a ≥4-fold decrease in C6 antibody titer with respect to a specimen taken at baseline (or during the early convalescent period if the baseline specimen was C6 negative) for all of the multiple-EM patients (P < 0.0001) and in 89% of the single-EM patients (P < 0.0001). These results indicate that a decline in anti-C6 antibody titer coincides with effective antimicrobial therapy in patients with early localized or early disseminated Lyme borreliosis. 相似文献
15.
16.
Dr. U. Cordes B. Braun M. Georgi F. Kümmerle V. Lenner E. Magin T. Philipp J. Beyer 《Journal of molecular medicine (Berlin, Germany)》1979,57(22):1209-1215
Zusammenfassung Bei sechs Patienten mit adrenalem Phäochromocytom erfolgte die Lokalisationsdiagnostik durch Ultraschalluntersuchung, Phlebographie der Nebennieren und selektiver Katecholaminbestimmung im Blut der Vena cava sowie der Nebennierenvenen. Durch die selektive Katecholaminbestimmung konnten alle Phäochromocytome lokalisiert werden, durch die Ultraschalluntersuchung fünf, durch die Phlebographie vier. Ein Phäochromocytom von 1,5 g Gewicht, das nur durch die selektive Katecholaminbe-stimmung, nicht aber durch Ultraschall oder Phlebographie lokalisiert wurde, konnte computertomographisch dargestellt werden.Um Fehldiagnosen bei der selektiven Katecholaminbestimmung zu vermeiden, darf vor der Blutentnahme aus den Nebennierenvenen kein Röntgenkontrastmittel injiziert werden, da dies zu einer erheblichen Adrenalin- oder Noradrenalinfreisetzung aus dem Nebennierenmark führen kann. 相似文献
17.
Cation channels,cell volume and the death of an erythrocyte 总被引:8,自引:0,他引:8
Lang F Lang KS Wieder T Myssina S Birka C Lang PA Kaiser S Kempe D Duranton C Huber SM 《Pflügers Archiv : European journal of physiology》2003,447(2):121-125
Similar to a variety of nucleated cells, human erythrocytes activate a non-selective cation channel upon osmotic cell shrinkage. Further stimuli of channel activation include oxidative stress, energy depletion and extracellular removal of Cl–. The channel is permeable to Ca2+ and opening of the channel increases cytosolic [Ca2+]. Intriguing evidence points to a role of this channel in the elimination of erythrocytes by apoptosis. Ca2+ entering through the cation channel stimulates a scramblase, leading to breakdown of cell membrane phosphatidylserine asymmetry, and stimulates Ca2+-sensitive K+ channels, thus leading to KCl loss and (further) cell shrinkage. The breakdown of phosphatidylserine asymmetry is evidenced by annexin binding, a typical feature of apoptotic cells. The effects of osmotic shock, oxidative stress and energy depletion on annexin binding are mimicked by the Ca2+ ionophore ionomycin (1 µM) and blunted in the nominal absence of extracellular Ca2+. Nevertheless, the residual annexin binding points to additional mechanisms involved in the triggering of the scramblase. The exposure of phosphatidylserine at the extracellular face of the cell membrane stimulates phagocytes to engulf the apoptotic erythrocytes. Thus, sustained activation of the cation channels eventually leads to clearance of affected erythrocytes from peripheral blood. Susceptibility to annexin binding is enhanced in several genetic disorders affecting erythrocyte function, such as thalassaemia, sickle-cell disease and glucose-6-phosphate dehydrogenase deficiency. The enhanced vulnerability presumably contributes to the shortened life span of the affected erythrocytes. Beyond their role in the limitation of erythrocyte survival, cation channels may contribute to the triggering of apoptosis in nucleated cells exposed to osmotic shock and/or oxidative stress. 相似文献
18.
Joachim Ktz Mathias Hahn Burkart Philipp Esen A. Bekturov Sarkyt E. Kudaibergenov 《Macromolecular chemistry and physics.》1993,194(2):397-410
Employing polyampholytes (inclusively polybetaines) of different chemical structure containing carboxylic groups and various basic nitrogen functions, homosymplex formation, as well as the competition between homo- and heterosymplex formation on addition of an appropriate polyelectrolyte, was investigated in dependence of pH and ionic strength by means of viscometry and turbidimetry. With most, but not with all, of the polyampholytes, the expected viscosity minimum at the isoelectric point, with its steepness depending on polyampholyte structure, was observed. Competition of homo- and heterosymplex formation at and near the isoelectric point is mainly governed by the pK values of the species involved, the level of zwitter-ion formation of the polyampholyte and the effect of non-Coulombic interactions, for example, via hydrogen bonds. 相似文献
19.
13C NMR spectroscopic studies on polyanion-polycation complexes and their component polyelectrolytes
Joachim Ktz Andreas Ebert Jürgen Kunze Burkart Philipp Johan Lindberg Kari Soljamo 《Macromolecular chemistry and physics.》1990,191(3):651-658
Position and intensities of the 13C NMR signals and relaxation times T1 of several anionic and cationic polyelectrolytes in the solid state were compared with those of the appropriate polyanion-polycation complexes. At a high charge density of the components, the most significant changes of the parameters in question due to complex formation are observed for the C atoms adjacent to the charge centers, indicating a strong Coulombic interaction. At lower charge density, conformational changes of the polymer chains have also to be taken into consideration. 相似文献
20.
C. de Wit Christian Schäfer Philipp von Bismarck Steffen-Sebastian Bolz Ulrich Pohl 《Pflügers Archiv : European journal of physiology》1997,434(4):354-361
We studied whether a flow-independent increase of luminal wall shear stress (WSS) could dilate hamster arterioles in vivo
and which endothelial mediators are potentially involved. To this end the plasma viscosity was elevated by exchanging blood
for dextran-erythrocyte solution thereby augmenting WSS. Diameters of small and large arterioles as well as red blood cell
velocities were measured before and after exchange of blood for solutions of identical haematocrit containing either high-
(HMWD) or low-molecular weight dextran (LMWD). The potential role of endothelial autacoids was investigated by local application
of the NO-synthase inhibitor N
G-nitro-L-arginine (L-NNA), the inhibitor of cyclooxygenase, indomethacin (3 μM), or the K+-channel blocker, tetrabutylammonium (TBA, 0.1 mM) to assess the potential effects of EDHF. HMWD (n = 11 animals) increased plasma viscosity by 64 ± 3% and dilated arterioles of all branching orders (A1–A4) significantly
[by 24 ± 3% (A1–A2) and 32 ± 3% (A3–A4)]. This dilation compensated fully for the calculated initial increase of WSS. LMWD
(n = 6) did not affect plasma viscosity or arteriolar diameters. Tissue treatment with L-NNA (30–300 μM, n = 12) substantially diminished the HMWD-induced dilation in small arterioles (A3–A4; to 13 ± 3%; P<0.05) and virtually abolished it in large ones (A1–A2). Consequently, the calculated WSS increased significantly in these
arterioles (by 31 ± 5%). TBA combined with L-NNA (n = 4) did not reduce further the remaining dilation. Indomethacin (n = 6) had no effect on HMWD-induced dilation. We conclude that an increase of WSS induces a mainly NO-mediated arteriolar
dilation. This dilation occurs in all arteriolar branching orders and is of sufficient magnitude to compensate for the initial
WSS-increase. Thus, any elevations of WSS fulfil the requirement for a signal to change diameter along the arteriolar tree
in a coordinated manner. The fully compensating dilation which we observed indicates that WSS is a controlled variable. It
does, however, raise questions as to its role as a continuous endothelial stimulus.
Received: 2 August 1996 / Received after revision: 24 February 1997 / Accepted: 14 April 1997 相似文献