Modulation of acetylcholine release by histamine in the nucleus accumbens.
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Biomedical subjects
Publications and source records attributed to H Fischer.
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INTRODUCTION: The relief of postoperative pain remains one of the most important goals for adequate surgical patient care. METHODS: Prospective, randomised, double-blinded study, including 118 patients (67 M;/ 51 F; median age 43 years, min. 18, max. 74). Two groups were formed. In the verum group a wound instillation with ropivacaine was performed, in the control group not. Intensity of pain, demand for analgesics and satisfaction of the patient were evaluated postoperatively. In 10 patients ropivacaine plasma levels were measured. RESULTS: Significant postoperative pain relief and a decrease in analgesic consumption were found on instillation of ropivacaine. Compared to the control group, patients receiving ropivacaine were significantly more satisfied with the postoperative pain management. Potential toxic plasma levels were not found. CONCLUSION: By the presented method, the surgeon actively contributes to a significant reduction in postoperative pain and analgesic consumption. Furthermore, the patient's benefit is reflected by higher satisfaction with the pain management. Complications due to toxic plasma levels are not seen.
OBJECTIVES: The aim of this study was to prove a nondestructive method to evaluate the strength of dental ceramic materials with respect to its potentiality and limitations. METHODS: The Young's moduli of 13 dental ceramic materials were determined by the resonance frequency method. Additionally, the flexural strengths of eight of these materials were evaluated by the four-point bending test. Strength values for the other five ceramic materials were taken from the literature. The Young's moduli were correlated with the strength values by Hook's law, respectively. RESULTS: Young's modulus for ceramics can be determined using a resonance frequency method. Fracture strain values of the ceramic materials tested (with the exception of Empress 2) have fracture strain values between 0.08 and 0.15%. A mean strain can be calculated (0.11%) and used with the value of Young's modulus to estimate fracture strength of ceramics. For the materials evaluated, predicted strength was within 39% of the measured values. SIGNIFICANCE: A non-destructive method to estimate strength of dental ceramic materials is possible, even though the accuracy of the predicted values is not very high. Nevertheless, the method permits new materials proposed for dental ceramic restorations to be screened for probable clinical success. Expensive and time-consuming testing would only need to be done on those materials which pass this initial criterion.
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In view of follow up, survey and development of therapeutic strategies for osteoarthritis where cartilage deterioration plays an important role, a non invasive, reliable and quantitative assessment of the articular cartilage is desirable. The currently available high resolution T(1)-weighted (T1-w) 3D FLASH pulse sequences with frequency selective fat suppression are very time consuming. We have 1) optimized a high resolution T1-w 3D FLASH water excitation (WE) sequence for short acquisition time and cartilage visualization, and 2) validated this sequence for cartilage volume and thickness quantification. The spectral fat presaturation was replaced by selective water excitation. The flip angle of the WE sequence was optimized for the contrast to noise (C/N(cart)) ratio of cartilage. Sagittal datasets (voxel size: 0.31 x 0.31 x 2 mm(3)) of the knees of nine healthy volunteers were acquired both, with the 3D FLASH WE (17.2/6.6/30 degrees ) sequence (WE) and a previously validated 3D FLASH fat saturated (42/11/30 degrees ) sequence (FS). For validation of the WE sequence, cartilage volume, mean and maximal cartilage thickness of the two sequences were compared. Reproducibility was assessed by calculating the coefficient of variation (COV %) of 4 consecutive WE data sets in the volunteers. The acquisition time was reduced from 16'30" (FS) down to 7'14" for the WE sequence. Image contrast and visualization of the cartilage was very similar, but delineation of the basal layer of the cartilage was slightly improved with the WE sequence. A flip angle of 30 degrees provided the best C/N(cart) ratios (WE). Reproducibility (COV) was between 1.9 and 5.9%. Cartilage volume and thickness agreed within 4% between FS and WE sequence. The WE sequence allows for rapid, valid and reproducible quantification of articular cartilage volume and thickness, prerequisites for follow-up examinations. The reduced acquisition time (50% of FS) enables routine clinical application and thus may contribute to a broader assessment of osteoarthritis.
In two-dimensionally separated Toxoplasma gondii lysate, mouse Th1 clone 3Tx15 detects two proteins of apparent molecular weight 40000 and pI of 5.8 and 5.9. Microsequencing of peptide fragments from tryptic digestion of one of these proteins yielded partial sequences of T. gondii lactate dehydrogenase (LDH)1. As shown by Western blot, toxoplasmic LDH co-migrates in two-dimensional gel electrophoresis with both T-cell antigenic proteins. With synthetic peptides spanning the complete primary structure of T. gondii LDH1, the T-cell epitope was mapped to a nine amino acid partial sequence which exhibits a motif for binding to I-E(k), the class II restriction element of antigen recognition by clone 3Tx15. From the two known isoforms of T. gondii LDH, clone 3Tx15 specifically recognises tachyzoite LDH1, but not bradyzoite LDH2, as shown with the corresponding epitope peptides and recombinant proteins. Antigen-presenting cells infected with live bradyzoites stimulate 3Tx15 T cells, while killed bradyzoites provide no antigenic stimulus. This finding implies that a transformation into the tachyzoite stage occurs in cells challenged with bradyzoites. Although LDH1 represents one major constituent of the tachyzoite proteome, the protein does not seem to be immunogenic in T. gondii infection of mice. This is evident from the lack of serum anti-LDH immunoreactivity and the failure of adoptively transferred 3Tx15 T cells to protect against lethal challenge. In conclusion, a T-cell-stimulatory Toxoplasma antigen is identified by means of a novel, high-resolution T-cell blot technique, the clones antigenic fine specificity allowing detection of parasite-stage conversion.
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Rotavirus (RV) is the most common cause of diarrheal illness in children. We report three solid-organ-transplanted patients in whom RV infection caused increased trough levels of the immunosuppressive macrolide tacrolimus (TAC) by mechanisms that are still under investigation. The virus was detected for longer in the feces of these patients than in infants not receiving immunosuppressive therapy. In association with short-term monitoring of blood trough levels of TAC, the dosage should be reduced early if symptoms of an acute gastroenteritis are present.
The combination of tacrolimus (TAC) and mycophenolate mofetil (MMF) is frequently used for immunosuppression after organ transplantation (Tx), but the pharmacokinetics and interactions between the two drugs are poorly elucidated. We describe here the increase of TAC trough levels during MMF-induced diarrhea in a 8-yr-old boy after kidney Tx. Early dose reduction of TAC, together with short-term monitoring of TAC trough levels in the presence of diarrhea, is recommended.
Fimbriae target bacteria to different mucosal surfaces and enhance the inflammatory response at these sites. Inflammation may be triggered by the fimbriae themselves or by fimbriae-dependent delivery of other host activating molecules such as lipopolysaccharide (LPS). Although LPS activates systemic inflammation through the CD14 and Toll-like receptor 4 (TLR4) pathways, mechanisms of epithelial cell activation by LPS are not well understood. These cells lack CD14 receptors and are unresponsive to pure LPS, but fimbriated Escherichia coli overcome this refractoriness and trigger epithelial cytokine responses. We now show that type 1 fimbriae can present an LPS- and TLR4-dependent signal to the CD14-negative epithelial cells. Human uroepithelial cells were shown to express TLR4, and type 1 fimbriated E. coli strains triggered an LPS-dependent response in those cells. A similar LPS- and fimbriae-dependent response was observed in the urinary tract of TLR4-proficient mice, but not in TLR4-defective mice. The moderate inflammatory response in the TLR4-defective mice was fimbriae dependent but LPS independent. The results demonstrate that type 1 fimbriae present LPS to CD14-negative cells and that the TLR4 genotype determines this response despite the absence of CD14 on the target cells. The results illustrate how the host "sees" LPS and other microbial products not as purified molecules but as complexes, and that fimbriae determine the molecular context in which LPS is presented to host cells.
Fimbriae mediate bacterial attachment to host cells and provide a mechanism for tissue attack. They activate a host response by delivery of microbial products such as lipopolysaccharide (LPS) or through direct fimbriae-dependent signalling mechanisms. By coupling to glycosphingolipid (GSL) receptors, P fimbriae trigger cytokine responses in CD14 negative host cells. Here we show that P fimbriae utilize the Toll-like receptor 4 (TLR4)-dependent pathway to trigger mucosal inflammation. Escherichia coli strains expressing P fimbriae as their only virulence factor stimulated chemokine and neutrophil responses in the urinary tract of TLR4 proficient mice, but TLR4 defective mice failed to respond to infection. Mucosal cells were CD14 negative but expressed several TLR species including TLR4, and TLR4 protein was detected. Infection with P fimbriated bacteria stimulated an increase in TLR4 mRNA levels. The activation signal did not involve the LPS-CD14 pathway and was independent of lipid A myristoylation, as shown by mutational inactivation of the msbB gene. Co-staining experiments revealed that TLR4 and the GSL receptors for P fimbriae co-localized in the cell membrane. The results demonstrate that P fimbriae activate epithelial cells by means of a TLR4-dependent signalling pathway, and suggest that GSL receptors for P fimbriae can recruit TLR4 as co-receptors.
This study focused on the contribution of different adrenoreceptor subtypes to the modulation of fictive swimming activity in a relatively simple, yet intact, lower vertebrate system, the immobilized Xenopus laevis tadpole and explored their possible role in mediating the noradrenergic modulation of spinal motor networks. In Xenopus embryos, near the time of hatching, activation of alpha(1) adrenoreceptors increased the duration of episodes of fictive swimming, whilst in larvae, 24 h after hatching, they were decreased. Activation of alpha(2) adrenoreceptors, however, markedly reduced episode duration at both developmental stages. Cycle periods in both stages were increased by the activation of alpha(1) and/or alpha(2) receptor subclasses, whereas beta adrenoreceptors were not apparently involved in the modulation of cycle periods or the duration of swim episodes. However, both beta and alpha(1) receptor activation decreased the intersegmental delay in the head-to-tail propagation of swimming activity, while alpha(2) receptors did not influence these rostro-caudal delays. Activation of neither alpha, nor beta, receptor subclasses had any consistent effect on the duration of ventral motor bursts. Our findings suggest that noradrenergic modulation of the swim-pattern generator in Xenopus tadpoles is mediated through the activation of alpha and beta adrenoreceptors. In addition, activation of particular receptor subclasses might enable the selective modulation of either the segmental rhythm generating networks, the intersegmental coordination of those networks or control at both levels simultaneously.
Collagen is the major component of the interstitial extracellular matrix (ECM). ECM is known to play an active role in numerous biological processes such as cell shape, proliferation, migration, differentiation, apoptosis as well as carcinogenesis. We used mRNA differential display RT-PCR to study differentially expressed genes in tissue samples from 24 colorectal cancers and four normal colon epithelia. Twenty of the 24 tumours showed expression of a gene COL11A1, not expressed in the normal samples. This gene is not normally expressed in adult colon tissue, but was here found to be expressed in 27 out of a total of 34 (79%) colorectal carcinomas. An analysis of other collagens showed that COL5A2 was not expressed in normal colon but was co-expressed with COL11A1 in the tumours. Our results suggest that stromal expression of COL11A1 and COL5A2 is associated with malignancy in colorectal cancer.
Austrian data underline that relying on the number of enterohemorrhagic Escherichia coli (EHEC) O157 strains isolated from clinical specimens does not allow assessment of the actual incidence of EHEC infections. A hospital-based system for identification of hemolytic-uremic syndrome cases based on voluntary cooperation was established in 1995 and provides information needed to monitor trends in the incidence of O157 and non-O157 EHEC infections.
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This study was designed to test the in vivo efficacy of the chemical chaperone trimethylamine oxide (TMAO) in correcting the Cl- transport defect in a mouse model of cystic fibrosis (CF). Rectal potential difference (RPD) measurements were done in matched wild-type and DeltaF508 CF mice. Mice were treated by subcutaneous injections of TMAO. Wild-type mice demonstrated a forskolin-stimulated, Cl--dependent hyperpolarization of -6.4 +/- 0.8 mV (n = 11), which was significantly increased to -13.1 +/- 1.4 mV after treatment with TMAO. DeltaF508 CF mice showed no significant responses to forskolin. Treatment with TMAO recovered a forskolin-activated RPD in DeltaF508 CF mice (-1.1 +/- 0.2 mV; n = 17) but not in CFTR null mice. The effects of TMAO were dose dependent, resulting in a slope of -0.4 +/- 0.1 mV x g(-1) x kg(-1) in DeltaF508 CF mice. The forskolin-stimulated RPD in TMAO-treated DeltaF508 CF mice was partially blocked by glibenclamide and further stimulated by apigenin. The total response to forskolin plus apigenin was -2.5 +/- 0.45 mV (n = 6 mice), corresponding to 39% of the response evoked by forskolin only in wild-type mice.
During walking, the six legs of a stick insect can be coordinated in different temporal sequences or gaits. Leg coordination in each gait is controlled and stabilized by coordinating mechanisms that affect the action of the segmental neuronal networks for walking pattern generation. At present, the motor program for single walking legs in the absence of movement-related coordinating intersegmental influences from the other legs is not known. This knowledge is a prerequisite for the investigation of the segmental neuronal mechanisms that control the movements of a leg and to study the effects of intersegmental coordinating input. A stick insect single middle leg walking preparation has been established that is able to actively perform walking movements on a treadband. The walking pattern showed a clear division into stance and swing phases and, in the absence of ground contact, the leg performed searching movements. We describe the activity patterns of the leg muscles and motoneurons supplying the coxa-trochanteral joint, the femur-tibial joint, and the tarsal leg joints of the middle leg during both walking and searching movements. Furthermore we describe the temporal coordination between them. During walking movements, the coupling between the leg joints was phase-constant; in contrast during searching movements, the coupling between the leg joints was dependent on cycle period. The motor pattern of the single leg generated during walking exhibits similarities with the motor pattern generated during a tripod gait in an intact animal. The generation of walking movements also drives the activity of thoraco-coxal motoneurons of the deafferented and de-efferented thoraco-coxal leg joint in a phase-locked manner, with protractor motoneurons being active during swing and retractor motoneurons being active during stance. These results show that for the single middle leg, a basic walking motor pattern is generated sharing similarities with the tripod gait and that the influence of the motor pattern generated in the distal leg joints is sufficient for driving the activity of coxal motoneurons so an overall motor pattern resembling forward walking is generated.
In the stick insect, Cuniculina impigra, intracellular recordings from mesothoracic motoneurons that control flexion and extension of the tibia and depression and levation of the trochantero-femur were made while the leg performed walking-like movements on a treadband or stereotyped rhythmic searching movements. We were interested in how synaptic input and intrinsic properties contribute to form the activity pattern of motoneurons during rhythmic leg movements without sensory feedback from other legs. During searching and walking, motoneurons expressed a rhythmic bursting pattern that was formed by a depolarizing input followed by a hyperpolarizing input in the inter-burst interval. This basic pattern was similar in all fast, semi-fast, and slow motoneurons that were recorded. Hyperpolarizations were in synchrony with activity in the antagonistic motoneurons. De- and hyperpolarizations were associated with a decrease in input resistance. All motoneurons showed spike frequency adaptation when depolarized by current injection to a membrane potential similar to that observed during walking. In the hyperpolarizing phase of fast flexor motoneurons, the initial maximum hyperpolarization was followed by a sag in potential toward more depolarized values. Consistent with this observation, only fast flexor motoneurons developed a depolarizing sag potential when hyperpolarized by injection of constant negative current.