Search PubMed⌕ Search

Biomedical subjects

C Unger

Publications and source records attributed to C Unger.

At least 145 records · Page 8Linked to original sources
PubMed1985

[Blood-brain barrier and the penetration of cytostatic drugs].

The penetration of 12 commonly used anticancer agents through the blood-brain barrier (BBB) was measured in a rat model using a single-injection tissue-sampling technique. Two of the tested drugs penetrated the barrier, but only to a limited extent. Entry of the drugs into the brain tissue critically depends on molecular weight and lipophilia of the respective test compound. For drugs with a molecular weight of less than 500, BBB simply behaves like an oil/water interphase, whereas drugs with a molecular weight greater than 500 are practically excluded from transport through the BBB even if they show a favourable oil/water partition coefficient. However, permeability of cytostatics was strongly increased if short chain alkylglycerols, up to final concentrations of about 0.3 mol/l were added to the injected solution. Under these conditions the Brain-Uptake-Index (BUI) reached values up to about 50% (cyclophosphamide), depending on lipid solubility and molecular dimension of the respective test compound and the alkyl chain length of the glycerol derivative.

Animals↗
PubMed1985

New assay for the O-alkyl cleavage enzyme with alkyl-lysophospholipids as substrates.

The O-alkyl cleavage enzyme is important for the metabolism of cytotoxic alkyl-lysophospholipids. We have developed a simple new method for the determination of the enzyme activity which is based on the formation of water-soluble phosphate during the enzyme reaction. This is the first assay which avoids the use of radiolabeled substrates.

Animals↗
PubMed1982

Absence of a direct role of phospholipid methylation in stimulus-secretion coupling and control of adenylate cyclase in guinea-pig and rat parotid gland.

The present study was undertaken to investigate a possible involvement of phospholipid methyltransferases in the coupling of receptor-mediated stimulation to secretion. Phospholipid methyltransferases were assayed in isolated parotid acini in the presence of carbamoylcholine or isoprenaline. Carbamoylcholine reduced the incorporation of methyl groups into phospholipids, whereas isoprenaline showed no effect. Amylase secretion stimulated either by carbamoylcholine or by isoprenaline could not be affected by inhibitors of methyltransferases (3-deaza-adenosine alone or plus homocysteine thiolactone) under conditions where phospholipid methylation was strongly inhibited. The activity of adenylate cyclase in isolated parotid microsomal membranes was not inhibited or stimulated by S-adenosyl-homocysteine or -methionine respectively. These results indicate that phospholipid methylation does not play an essential role in stimulus-secretion coupling in the parotid gland.

Adenylyl Cyclases↗
PubMed1980

Specific protein phosphorylation during stimulation of amylase secretion by beta-agonists or dibutyryl adenosine 3',5'-monophosphate in the rat parotid gland.

The present study was undertaken in order to examine the possible involvement of protein phosphorylation during beta-adrenergic stimulation in the rat parotid gland. Isolated parotid gland slices were stimulated by either isoproterenol or dibutyryl adenosine 3',5'-monophosphate (Bt2cAMP) in the presence or absence of propranolol. Amylase output was measured as a parameter for the degree of stimulation of secretion. Stimulation of secretion by either isoproterenol or Bt2AMP was associated with phosphorylation of three protein bands as revealed by sodium dodecylsulfate/polyacrylamide gel electrophoresis and autoradiography. The apparent molecular weights of the three proteins were 35,100 (protein I), 25,700 (protein II) and 20,400 (protein III). After cell fractionation by differential and gradient centrifugation, protein I was enriched in a light membrane fraction most likely corresponding to the plasma membrane as revealed by marker enzyme analysis. Proteins II and III were recovered in a denser fraction containing mainly mitochondria and rough microsomes. The effect of isoproterenol but not that of Bt2cAMP on phosphorylation of all three protein bands was completely abolished by propranolol. The different time course in the stimulation of amylase secretion by isoproterenol and Bt2cAMP respectively was reflected by corresponding differences in the time course of protein phosphorylation.

Amylases↗
PubMedDate not supplied

Angiogenesis as a target for tumor treatment.

Angiogenesis is a key step in tumor growth, invasion and metastasis. Thus, antiangiogenic therapy was postulated to be an attractive approach for antitumor treatment. Based on today's knowledge, at least three strategies for inhibition of angiogenesis are feasible: (1) inhibition of release of angiogenic factors from tumor cells and/or neutralization of angiogenic molecules that have already been released: (2) inhibition of vascular endothelial cell proliferation and migration, and (3) inhibition of the synthesis and turnover of vessel basement membrane. To date, a number of antiangiogenic agents have been identified. In animal models, treatment with angiogenesis inhibitors has proven antitumor effects. Early clinical experience with angiogenic inhibitors indicates that optimal antiangiogenic therapy in the future is likely to be based on the long-term administration to cancer patients in adjunct to surgery, radiotherapy and conventional chemotherapy.

Animals↗
PubMedDate not supplied

Antitumor activity and induction of apoptosis by water-soluble derivatives of 7 beta-hydroxycholesterol in human colon carcinoma cell lines.

At present, cancer therapy of solid tumors, such as lung and colorectal cancer, is unsatisfactory. Recently, oxygenated sterols have shown selective cytotoxicity against tumor cells. In this study, the cytotoxicity of 7 beta-hydroxycholesterol (7 beta HC) and two water-soluble derivatives of 7 beta HC, i.e. 7 beta HC-bis-hemisuccinate [disodium salt] (7 beta HC-HS) and 7 beta HC-bis-hemisuccinate-diethanolaminoate (7 beta HC-EA), was determined in DLD-1, KM20L2, HCT-116, HT-29 and SW620 colon carcinoma cell lines using a cell count assay. IC50 values of the two water-soluble derivatives were, on the whole, comparable to 7 beta HC lying in the range of 3-10 microM. In addition, the water-soluble derivatives were able to induce apoptosis in the examined DLD-1 and KM20L2 colon carcinoma cell lines in contrast to the parent compound 7 beta HC, as shown by DNA fragmentation, by the cleavage of DNA repair enzyme poly(ADP) ribose polymerase (PARP), and by the proteolytic cleavage of caspase-3 (CPP32). Due to the improved water-solubility of 7 beta HC-HS and 7 beta HC-EA and their promising antitumor activity in vitro, animal studies in suitable tumor models are warranted.

Antineoplastic Agents↗
PubMedDate not supplied

Stimulation of human hematopoietic progenitor cells by the alkylphosphocholines hexadecylphosphocholine and hexadecyl-N,N,N-trimethyl-hexanolamine.

Hexadecylphosphocholine (HePC) represents a new class of membrane-active antitumoral compounds, the alkylphosphocholines. In vivo studies of HePC showed an increase in the total white blood count (WBC) in the highest dosage group in DMBA-induced breast carcinoma in the rat. In phase II studies most of 70 patients treated orally with HePC likewise showed a significant increase in WBC and a rise in platelet count. The present investigation on human bone marrow progenitor cells from 42 patients shows a dose-dependent and selective co-stimulatory effect of HePC on the G-CSF-dependent growth of bone marrow progenitor cells in progenitor cells from 22 patients. Hexadecyl-N,N,N-trimethyl-hexanolamine(HePC6), which has no, or only marginal antitumoral activity but comparable physicochemical properties to HePC, also stimulates the G-CSF-dependent colony formation in a dose-dependent manner. The molecular mode of action of the stimulating effect of HePC on G-CSF-dependent colony formation is not entirely understood. An inhibitory effect of HePC and ether lipids on protein kinase C (PKC) has been described. However, there also is evidence that etherlipids can stimulate PKC, which plays a crucial role in proliferation and survival of hematopoietic cells, under more physiological conditions. Therefore, the most likely explanation for the stimulating effect of HePC on G-CSF-dependent colony formation might be interference with signal transduction pathways.

Adult↗
PubMedDate not supplied

Hexadecylphosphocholine: determination of serum concentrations in rats.

A sensitive and quantitative determination of the concentration of hexadecylphosphocholine in serum is described. After HPLC separation, the concentration of hexadecylphosphocholine is determined by phosphate analysis. According to this method, the half-life of hexadecylphosphocholine in serum rats is about 96 h. A steady-state serum concentration of 110 microM is reached after 2 weeks of daily treatment with 10 mg/kg hexadecylphosphocholine. The described method has general application for other compounds with similar structures. For instance, serum levels of alkyllysophosphocholines such as 1-0-octadecyl-2-0-methyl- racglycero-3-phosphocholine can be determined using this method.

Animals↗
PubMedDate not supplied

[Sodium concentration and pre-eclampsia: is salt restriction of value?].

UNLABELLED: The significance of sodium metabolism with respect to preeclampsia is discussed in the literature with a wide range of diverging opinions. The presented work analyses the influence of a low salt diet on the symptoms of preeclampsia and the consequences for the newborn. MATERIAL AND METHODS: 160 patients with preeclampsia between 1989 and 1993 were retrospectively studied. Serum sodium values (at hospital admission, lowest prepartal level, immediate and 3-8 days postpartum) were compared with the corresponding gestosis symptoms. RESULTS: The mean sodium serum concentration at admission was 135.6 mmol/l (lower norm: 136 mmol/l). This was significantly different from the mean lowest prepartal value of 134.9 mmol/l (p < 0.0001). Postpartum the mean fell again significantly to 134.0 mmol/l (p < 0.0001). None of the parameters for gestosis symptoms, which were investigated (diastolic blood pressure, edema, proteinuria, serum protein levels and hyperreflexia) showed any statistically significant association with the serum sodium concentration. Five patients had very low serum natrium values, 130 mmol/l, either at admission or during hospitalisation. Three of the five infants of these patients had hyponatremia; two needed sodium supplementation. CONCLUSION: There seems to be no reason supporting a low salt diet as therapy for preeclampsia, since it does not affect the symptoms and might lead to hyponatremia in the newborn.

Adult↗