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H Lentzen

Publications and source records attributed to H Lentzen.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cisplatin nephrotoxicity and protection by silibinin.

BACKGROUND: The anticancer drug cisplatin is know to have toxic side-effects on different segments of the nephron. The flavonoid silibinin has previously been shown to be protective in models of hepatotoxicity. The aim of the present study was to evaluate, whether silibinin can also ameliorate alterations in renal glomerular and tubular function and tubular morphology induced by cisplatin. METHODS: In a rat model renal damage was induced by a single injection of cisplatin (5 mg/kg body weight). The protective effects of silibinin were studied in rats that received the flavonoid (200 mg/kg body weight, i.v.) 1 h prior to the administration of cisplatin. Kidney function was monitored by analysing urinary markers of glomerular and tubular function over a period of 11 days. Animals of a second group, with identical treatment, were sacrificed 4 days after drug application for an evaluation of tubular morphology at the light-microscopical level. RESULTS: Administration of cisplatin caused a decline in kidney function within a day following treatment. Symptoms observed were for example decreases in creatinine clearance and increases in proteinuria, in the urinary activity of the proximal tubular enzymes alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase and in renal magnesium wasting. The effects of cisplatin on creatinine clearance and proteinuria were totally prevented by a pretreatment of the animals with silibinin. Impairment of proximal tubular function was ameliorated, that is enzymuria and magnesium wasting was less pronounced. Silibinin alone had no effect on kidney function. Treatment with silibinin distinctly diminished morphological alterations observed in the S3-segment of the proximal tubule 4 days after cisplatin administration. CONCLUSION: The effects of cisplatin on glomerular and proximal tubular function as well as proximal tubular morphology could totally or partly be ameliorated by silibinin. It is concluded the silibinin can act as a nephroprotectant and it is suggested that it could have beneficial effects on the kidney in clinical settings.

Acetylglucosaminidase↗
PubMed1996

Stimulation of cytokine production via a special standardized mistletoe preparation in an in vitro human skin bioassay.

The mistletoe preparation Lektinol is standardized with respect to bioactive mistletoe lectin, the active component of mistletoe. This standardized mistletoe preparation and its active components (mistletoe lectins) were compared in the skin2 bioassay in vitro for their capacity to stimulate interleukin 1 alpha and interleukin 6 release from skin analogue tissue, composed of human cells in their naturally secreted matrix. The standardized mistletoe preparation, its basic ingredient, aqueous mistletoe extract, and pure mistletoe lectins all stimulated IL-1 alpha and IL-6 release from skin2 tissues during 24 h incubation. The amounts of cytokines released from various skin2 tissue lots by mistletoe lectin I (ML I) (0.75-8.0 ng/ml) and by the standardized mistletoe preparation remained relatively constant across a series of different batches. Concentration-response curves to the standardized mistletoe preparation and ML I were similar for IL-1 alpha and IL-6 release. The importance of the concentration of mistletoe lectins for the cytokine-releasing action of the standardized mistletoe preparation was confirmed using a neutralizing anti-mistletoe lectin antiserum. CONCLUSIONS. Using the skin2 method it was shown that reproducible stimulation of cytokine release by a standardized mistletoe preparation from batch to batch is one of the notable features of its pharmaceutical quality. This standardized mistletoe preparation therefore represents a preparation with constant immunobiological effects. Mistletoe lectins of the standardized mistletoe preparation are the active substances in the skin2 bioassay. The skin2 method is a reliable quantitative bioassay for determination of immunopharmacological effects.

Biological Assay↗
PubMed1996

Stimulation of neutropoiesis by a special standardized mistletoe preparation after cyclophosphamide chemotherapy in mice.

Lektinol, is a special mistletoe preparation (SMP) with immunostimulatory activity, standardized with respect to bioactive mistletoe lectin, one of the most active components of mistletoe. In the present study, stimulation of leukopoiesis by SMP was investigated in mice after induction of myelosuppression by the cytostatic agent cyclophosphamide (CP). Under the experimental conditions described, CP induced severe leukopenia followed by a recovery phase where leukopoiesis was distinctly enhanced in mice treated additionally with SMP at daily intravenous doses in a range of 30 to 5000 microliters/kg body weight. This phenomenon was mainly due to a stimulation of granulopoiesis resulting in a stronger increase of metamyelocyte and mature neutrophil counts in the peripheral blood.

Animals↗
PubMed1995

A plant lectin derived from Viscum album induces cytokine gene expression and protein production in cultures of human peripheral blood mononuclear cells.

A plant lectin from Viscum album (ML-I) has been shown to increase the number and cytotoxic activity of natural killer cells and to induce antitumor activity in animal models. However, the mechanisms underlying the effects of ML-I on natural host defenses are unknown. After 24 h incubation of peripheral blood mononuclear cells in the presence of 10 and 1 ng/ml of ML-I, mRNA expression and secretion of a panel of cytokines were evaluated by reverse polymerase chain reaction and by ELISA, respectively. The lectin induced expression of interleukin (IL)-1 alpha, IL-1 beta, IL-6, tumor necrosis factor-alpha, interferon-gamma, granulocyte-monocyte colony-stimulating factor and IL-10 genes but no expression of IL-2 and IL-5 genes could be detected. Regarding cytokine secretion, IL-6 and TNF-alpha production was induced by 10 ng/ml ML-I. On the other hand, IL-10 secretion was only stimulated by 1 ng/ml lectin. No production of IFN-gamma or, as expectable, IL-2 could be detected. In addition, ML-I increased the percentage of HLA-DR+ T lymphocytes in vitro. In tests performed on whole blood, monocytes and granulocytes bound the fluorescence-conjugated ML-I molecules to a higher degree than lymphocytes. Expression of IL-1 beta and IFN-gamma genes could also be observed upon ML-I stimulation of nonadherent cells. These results suggest that lectin-sugar interactions on the cell surface of immunocompetent cells can induce cytokine gene expression and protein synthesis.

Cells, Cultured↗
PubMed1986

Characterization of the enkephalin-degrading aminopeptidase of neuroblastoma (N1E-115) cell membranes.

A membrane-bound enkephalin (ENK) -hydrolyzing amino-peptidase (AP) was partially purified from neuroblastoma (clone N1E-115) cell membranes; enzyme activity was assayed by determination of the leu-enkephalin (LENK) degradation product, tyrosine (Tyr), with HPLC. The enzyme was extracted with Triton X-100, resolved by anion-exchange chromatography and further purified by gel filtration. The overall purification was about 100-fold with a yield of 43%. The apparent Mr value of the AP by gel filtration in the presence of 0.3% Triton X-100 was approx. 400 kDa. In the absence of detergent the apparent Mr value was about 305 kDa. In the elution buffers, where Triton X-100 was omitted, the peptidase activity was lost. The enzyme had a Km of 0.13 mM and a Vmax of 450 nmoles per mg protein per min at 25 degrees C for LENK and exhibited little sensitivity to bestatin (IC50: 200 microM) and puromycin (IC50: 500 microM), but it was strongly inhibited by amastatin (IC50: 8 microM). The enzyme is an amphiphilic membrane protein; the native primary structure is preserved only in the 'detergent form'. It seems to be AP N (EC 3.4.11.2) with an optimum of pH 7.2 to 7.4. We assume that this AP plays the important role in inactivating ENKs on the neuronal level. The ENK-degrading AP, partially purified from primary rat brain astrocyte cell membranes, exhibited a smaller apparent Mr value (130 kDa) and a higher sensitivity to amastatin (IC50: 0.4 microM), bestatin (IC50: 90 nM) and puromycin (IC50: 5 microM) than did the N1E-115 enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Isolation and characterization of internalized glioma cell membranes.

A method for isolating plasma membranes based on the ability of cultured C6-glioma cells to phagocytize inert material such as polystyrene (latex) beads is described. The beads (phi 1.1 micron) were incubated for 16 h or 5 h. After several washings and homogenization of the cells, the beads with the surrounding membranes were isolated by use of a sucrose density gradient. The membranes were analyzed morphologically and biochemically. Morphological studies by means of light- and electron microscopy confirmed the intracellular localization of the beads. Enzymatic studies revealed that the specific activity of acid phosphatase decreased with shorter incubation periods (from 268.00 +/- 38.56 U X mg protein-1 X min-1 after 16 h to 125.12 +/- 9.10 after 5 h), whereas that of Na, K-ATPase showed the opposite trend (3.63 +/- 0.41 and 4.73 +/- 0.78 mumoles phosphate X mg protein-1 X h-1, respectively), indicating a lesser contamination with lysosomes. The main advantages of this procedure for membrane studies lie in purity and definite orientation ("inside-out") of the membranes.

Acid Phosphatase↗
PubMed1984

Enkephalin degradation by enkephalinergic neuroblastoma cells. Involvement of angiotensin-converting-enzyme.

Degradation of tritiated [Leu5]enkephalin was studied in cultures of neuroblastoma cells (clone N1E-115). Incubation of cells in suspension revealed Tyr as the main tritiated metabolite; however, Tyr-Gly-Gly and Tyr-Gly were detectable as well. In a crude membrane preparation of the neuroblastoma cells the level of Tyr is reduced to 13% and that of Tyr-Gly to 10% of the initial value, whereas Tyr-Gly-Gly is increased to about 5 times the initial value. Of the degraded enkephalin, 66% was accounted for by the formation of Tyr, 30% by the formation of Tyr-Gly-Gly and 4% by the formation of Tyr-Gly. The production of Tyr was inhibited by bestatin, an inhibitor of aminopeptidases, and that of Tyr-Gly-Gly by captopril, an inhibitor of angiotensin-converting-enzyme. The results prove the ability of neuroblastoma cells (N1E-115) to degrade enkephalin by aminopeptidase and the membrane-bound angiotensin-converting-enzyme.

Aminopeptidases↗
PubMed1984

Angiotensin-converting enzyme, enkephalinase A and aminopeptidases in the breakdown of enkephalin--studies in cell cultures.

Neuroblastoma cells (N1E-115) and glial cells possess aminopeptidases, dipeptidyl carboxypeptidases and dipeptidyl aminopeptidases, which are located in the plasma membranes. Neuronal cells possess angiotensin-converting enzyme (ACE), which splits the Gly-Phe bond and generates Tyr-Gly-Gly from enkephalin. They have no enkephalinase A. In contrast, glial cells possess enkephalinase A but no ACE. Not only the dipeptidyl carboxypeptidases on neuronal and glial cells are different. These cells have aminopeptidases which have to be distinguished as well. This differentiation is made by using bestatin as an aminopeptidase inhibitor and reveals peptidases of high and poor bestatin-sensitivity.

Aminopeptidases↗
PubMed1983

Localization of the thiorphan-sensitive endopeptidase, termed enkephalinase A, on glial cells.

Degradation of tritiated Leu-enkephalin was studied in cultures of primary astrocytes from rat brain. The incubation experiments with a cell suspension revealed Tyr as the main tritiated metabolite; however, Tyr-Gly-Gly and Tyr-Gly were detectable as well. Using a crude membrane preparation of the astrocytes, we found about equal amounts of Tyr and Tyr-Gly-Gly but only trace quantities of Tyr-Gly. The production of Tyr was completely inhibited by bestatin, an inhibitor of aminopeptidases, that of Tyr-Gly-Gly by thiorphan, a specific inhibitor of enkephalinase A. The results prove the ability of glial cells to degrade enkephalin by aminopeptidase and a membrane-bound enkephalinase A.

Aminopeptidases↗
PubMed1983

No evidence for enkephalinase A on neuronal cells.

It is generally assumed that enkephalinase A, a highly thiorphan-sensitive dipeptidylcarboxypeptidase cleaving the Gly-Phe bond during enkephalin degradation, is bound to the neuronal membrane. To clarify the localization of the enzyme, we used three neuron-like models (neuroblastoma cells N1E-115, bulk prepared neurons and neurons in primary culture) and three glial models (astrocytes from rat brain and from chick embryo brain in primary culture and bulk prepared glial cells). After incubating membranes and cells with (Leu5)-enkephalin, we found that, contrary to the present opinion, the enkephalinase A is located on the glial cells, whereas the neuronal cells possess angiotensin-converting enzyme.

Animals↗
PubMed1981

[Comparative study of serum levels and urinary excretion following oral administration of paromomycin and neomycin (author's transl)].

In a comparative study absorption and elimination characteristics of p.o. administered paromomycin and neomycin were investigated in healthy volunteers and patients with liver cirrhosis and/or portocaval shunt. Serum and urine concentrations were determined by means of the diffusion test. 1. In a cross-over study 6 volunteers were each administered single p.o. doses of 14.28 g paromomycin sulfate (= 10 g free base = 1.6 X 10(-2) mol) and 16 g neomycin sulfate (= 10.65 g free base = 1.7 X 10(-2) mol). Following these virtually equimolar doses AUC values of neomycin were 2.5 times as high as those of paromomycin (p less than 0.01). Paromomycin serum level time courses could be described by an open one-compartment model with a mean half-life of 2.6 h (harmon. mean). Mean computed maximum levels of 3.6 microgram/ml appeared on an average of 1.9 h after administration. After 32 h the mean recovery in urine was 0.2%. 5 volunteers showed a similar behavior with a mean excretion of 0.1%, whereas one person excreted 0.8% in urine. The time course of neomycin was evaluated according to an open two-compartment model with a distribution half-life of 1.5 h and a terminal half-life of 9 h (harmon. means). Mean computed maximum levels of 5.1 microgram/ml appeared on an average of 2.6 h after administration. The mean lag time was 1.3 h. 32 h after administration 0.3% of the dose were detected in urine. 2. Patients with cirrhosis and/or portocaval shunt were treated with 8 capsules/d of either 357.1 mg paromomycin sulfate or 250 mg neomycinsulfate each over a period of 7 days. Despite the lower dose of neomycin comparable serum levels of both aminoglycosides were observed. This result can be explained by a lower elimination rate and a higher extent of accumulation of neomycin. Mean amounts excreted in the urine of the 7th day were 0.1% for paromycin and 0.2% for neomycin.

Adult↗
PubMed1976

Competition of some biogenic amines for uptake into synaptic vesicles of the striatum.

Synaptic vesicles were isolated from the caudate nucleus of the pigs by differential centrifugation and incubated with labelled monoamines in the absence or in the presence of ATP-Mg(2+). Addition of ATP-Mg(2+) enhanced the uptake of (14)C-dopamine into the vesicles. Serotonin competitively inhibited the ATP-Mg(2+)-dependent uptake of (14)C-dopamine without influencing the uptake which took place in the absence of ATP-Mg(2+). Likewise, dopamine caused a dose-dependent inhibition of the ATP-Mg(2+)-dependent uptake of (14)C-serotonin without inhibiting the uptake in the absence of ATP-Mg(2+). Incubation of the vesicles with equal concentrations of(3)-dopamine and (14)C-serotonin revealed that the presence of the one amine competitively inhibited the ATP-Mg(2+)-dependent uptake of the other. Tyranimine competitively inhibited the ATP-Mg(2+)-dependent uptake of (14)C-dine, (14)C-serotonin and (14)C-noradrenaline into the vesicles; the uptake of the amines which took place in the absence of ATP-Mg(2+) was not impairedby tyramine. Analysis of the amine uptake by the ABC test showed that a mutual inhibition exists between dopamine and serotonin for the uptake into the synaptic vesicles. GABA did not influence the uptake of (14)C-dopamine either in the absence, or in the presence of ATP-Mg(2+)...

Adenosine Triphosphate↗