Biomedical subjects

S Uhlig

Publications and source records attributed to S Uhlig.

62 records · Page 4Linked to original sources

PubMed1992

Granulocyte colony-stimulating factor treatment protects rodents against lipopolysaccharide-induced toxicity via suppression of systemic tumor necrosis factor-alpha.

Pretreatment with recombinant human granulocyte CSF (G-CSF) protected mice in two different models of septic shock. Intravenous injection of 250 micrograms/kg G-CSF to mice prevented lethality induced by 5 mg/kg LPS. Injection of 50 micrograms/kg G-CSF protected galactosamine-sensitized mice against LPS-induced hepatitis. In either case, this protection was accompanied by a suppression of LPS-induced serum TNF activity. In contrast, when galactosamine-sensitized mice were pretreated with 50 micrograms/kg murine recombinant granulocyte/macrophage CSF instead of G-CSF and subsequently challenged with LPS, serum TNF activity was significantly enhanced and mortality was increased. The suppressive effect of G-CSF on LPS-induced TNF production was also demonstrated in rats. In vivo, no TNF was detectable in the blood of LPS-treated rats, which had been pretreated with G-CSF. Ex vivo, alveolar macrophages, bone marrow macrophages, Kupffer cells, or peritoneal macrophages prepared from G-CSF-treated rats produced significantly less TNF upon stimulation with LPS than corresponding populations from control rats. However, when these macrophage populations were incubated with G-CSF in vitro, LPS-induced TNF production was unaffected. These data suggest that the G-CSF-mediated suppression of TNF production is not a direct effect of G-CSF on macrophages. To examine whether, independent of the protection against LPS, G-CSF treatment still activated neutrophils, it was demonstrated that granulocytes from G-CSF-treated rats were primed for PMA-induced oxidative burst and for ionophore/arachidonic acid-stimulated lipoxygenase product formation. The experiments of this study support the notion that G-CSF is a negative feedback signal for macrophage-derived TNF-alpha production during Gram-negative sepsis.

Animals↗

PubMed1992

The physiological consequences of glutathione variations.

The major low molecular weight thiol inside cells, the tripeptide glutathione (GSH), is of importance for protection of the cell against oxidative challenge, for thiol homeostasis required to guarantee basic functions, and for defence mechanisms against xenobiotics. Since the pathophysiological significance of a perturbed GSH status in human disease is less clear, this review evaluates the consequences of in vivo variations of GSH. Owing to intracellular GSH concentrations above 2 mM depletion of GSH as such has little metabolic consequences unless an additional stress is superimposed. The kinetic properties of GSH-dependent enzymes imply that loss of up to 90% of intracellular GSH may still be compatible with cellular integrity. Mitochondrial GSH, which accounts for about 10% of total cellular GSH, may define the threshold beyond that toxicity commences. Thus, in cases of severe GSH-depletion a substitution of GSH as a therapeutic measure seems justified. Such a severe depletion of GSH has been described for some diseases such as liver dysfunction, AIDS or pulmonary fibrosis.

Animals↗

PubMed1991

Participation of interneurons in penicillin-induced epileptic discharges.

Interneurons of rat motor cortex in vivo and of rat hippocampal slices were studied during penicillin-induced epileptic discharges. Synchronous with pyramidal cells, they showed transient depolarizations similar to paroxysmal depolarization shifts in pyramidal cells. The transient depolarizations were followed by hyperpolarizing or depolarizing afterpotentials lasting 600 to 1200 ms. During the transient depolarizations and the afterdepolarizations the interneurons discharged with increased frequency. This may contribute to the enlarged and prolonged synaptic inhibitions following interictal discharges in pyramidal cells.

Animals↗

PubMed1990

Glutathione enhancement in various mouse organs and protection by glutathione isopropyl ester against liver injury.

Intraperitoneal administration of glutathione isopropyl ester to fasted, male NMRI mice dose dependently increased the glutathione concentration in various organs. Administration of 1 g/kg glutathione isopropyl ester led to the following increases: liver 166%; lung 164%; heart 121% after 4 hr; and brain 133% after 6 hr. Spleen, kidney, muscle, serum and blood cell glutathione were not affected by the treatment. Pretreatment with glutathione isopropyl ester was found to protect against paracetamol- or allyl alcohol-induced liver damage. Following treatment with the ester a significant correlation between protection against liver damage and enhancement of liver glutathione content was obtained. The dose dependence of this protection was studied.

1-Propanol↗

PubMed1989

Separation of different types of afterpotentials following penicillin-induced paroxysmal depolarization shifts of neurons in the motor cortex of the rat.

Afterpotentials of penicillin-induced paroxysmal depolarization shifts (PDS) of neurones in the motor cortex of the rat in vivo were investigated with intracellular recordings. Following the PDS, 4 different types of afterpotentials were observed: fast afterhyperpolarizations with an average duration of 600 ms, fast afterdepolarizations with an average duration of 700 ms, slow afterhyperpolarizations with an average duration of 1.9 s and slow afterdepolarizations with an average duration of 1.8 s. The fast and slow afterpotentials could occur in various combinations with the exception of a fast afterhyperpolarization followed by a slow afterdepolarization. Neurones displaying afterdepolarizations had higher resting membrane potentials than those displaying afterhyperolarizations, i.e. the polarity of the afterpotential depended on membrane potential. Experiments with intracellular Cl- injection indicated that the fast but not the slow afterpotentials are associated with an increase in membrane Cl- conductance. The slow afterhyperpolarizations are suggested to result from a calcium-dependent or a synaptically generated potassium current.

Animals↗

PubMed1988

Miniature endplate potentials as a tool in neurotoxicology.

The toxic effect of thallium added to the bath solution was studied with intra- and extracellular recordings from mammalian nerve-muscle preparations. To elucidate the target region, 3 different functional parameters were studied: (1) Post-synaptic endplate potentials (EPPs) resulting from evoked transmitter release; (2) Post-synaptic miniature endplate potentials (MEPPSs) resulting from spontaneous transmitter release; and (3) Presynaptic ion currents at the nerve terminal. At a concentration of 0.5 mM/l thallium acetate, EPP amplitudes were irreversibly decreased while MEPP amplitudes remained unaffected. MEPP frequencies were reversibly increased, indicating a presynaptic rather than a post-synaptic target site of thallium toxicity. The subpopulation of small MEPPs (sub-MEPPs) behaved like the MEPP population, except that upon addition of 4-AP, the sub-MEPP population was augmented at the cost of the MEPP population. In view of the slow time course of the toxic effects (30 min for a 10-fold increase of MEPP frequency, 100-180 min for a 50% reduction of EPP amplitudes), it is concluded that thallium needs to be transported across the cell membrane before it finally interferes with release mechanisms. It is hypothesised that thallium reduces the number of active sites recruited by one action potential (reduced EPP amplitude), while at the same time the probability of transmitter liberation is enhanced (increased MEPP frequency). The rather indirect mode of action of thallium was also found when presynaptic ion currents were recorded using extracellular electrodes. In proportion to the decrease of the EPP amplitudes, a reduction of all inward and outward currents was observed. This effect was also irreversible. It is concluded that in spite of some similarities, thallium behaves quite differently from bivalent heavy metals like cobalt and cadmium, which act as competitive calcium antagonists at the presynaptic nerve terminal. In these toxic substances, the time course of intoxication is much faster, the required concentration is much lower, and the inhibition of the slow calcium current is reversible.

4-Aminopyridine↗

PubMed1980

[Autoantibodies in malignant tumors].

Autoimmune phenomena are to be referred to the possible immune reactions of the host organism in malignant tumours. By means of the indirect immune fluorescence method in 95 sera of patients with tumours and a control group 0f 30 blood donors was sought for autoantibodies against mitochondria, nuclear factors, smooth musculature, myocardium, delomorphous cells. In the blood donors in one case autoantibodies against the myocardium could be proved, the tumor group, however, revealed positive findings of autoantibodies in 25 patients, which are statistically significant (p < 0.05). In the individual groups of diagnosis the acute myeloic leukaemia, the IgG-plasmocytoma and the cervical carcinoma showed a highly significant positive proof reaction compared with the control. The titres lie in their highest values at 1 : 64, in most cases at 1 : 16 and 1 : 32 and speak for an accompanying reaction are epiphenomenon. Autoantibodies against mitochondria were in no case found against smooth musculature in all positive groups. Apart from the absence of antibodies against delomorphous cells in gynaecological tumours the differentiation of types of autoantibodies do not show a reference to kind of tumour and localisation. The proof of autoantibodies in malignant tumours should be used for the judgment of the immune state

Antibodies, Neoplasm↗

PubMedDate not supplied

The action of cobalt, cadmium and thallium on presynaptic currents in mouse motor nerve endings.

The action of cobalt, cadmium and thallium on presynaptic currents was investigated by recording extracellular potentials from mouse motor nerve terminals. Recorded waveforms consisted of two negative deflections preceded by a small positivity. The second negative deflection could be blocked by the potassium channel blockers tetraethylammonium (TEA) and 3,4-diaminopyridine (3,4-DAP). Application of either divalent cations (cobalt, cadmium) or monovalent thallous ions to the bath, even in mM concentrations, did not change these waveforms significantly. After application of high TEA and 3,4-DAP concentrations (10 mM and 250 microM, respectively), a prolonged positive-going wave arose, which could be blocked reversibly by bath application of cobalt and cadmium, but not thallium. The concentration-inhibition curve for cadmium suggested two apparent dissociation constants, whereas cobalt seemed to have only one apparent dissociation constant. It was concluded that the long-lasting positive wave is driven by calcium influx, since it was competitively antagonized by the application of cobalt and cadmium. A different, short-lasting positive wave arose using lower concentrations of potassium channel blockers, and this wave could not be blocked by cobalt, cadmium, or thallium.

4-Aminopyridine↗