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Biomedical subjects

D Arndt

Publications and source records attributed to D Arndt.

At least 37 records · Page 2Linked to original sources
PubMed1993

Antineoplastic activity in vitro of free and liposomal alkylphosphocholines.

We investigated the liposome forming properties of three homologues of alkylphosphocholines: hexadecylphosphocholine (HPC), octadecylphosphocholine (OPC) and eicosanylphosphocholine (EPC). In the presence of cholesterol and dicetylphosphate, alkylphosphocholines form liposomes with slow permeability for entrapped carboxyfluorescein. We studied the direct cytotoxicity of alkylphosphocholine vesicles and their ability to attack MethA sarcoma cells, human skin and muscle fibroblasts (M22, GUS, Moscow), and human mouth epidermoid carcinoma cells (KB, ATCC, CCL 17). All alkylphosphocholines show cytotoxic activity against the investigated cells, the degree of which depends on the number of carbon atoms in the alkyl chain, concentration and incubation time. Whereas the etherlipid liposomes are less toxic to MethA cells than the free compounds, the liposomal alkylphosphocholines are more toxic toward KB and M22 cells than the corresponding free lipids.

Animals↗
PubMed1991

Antitumor effects of alkylphosphocholines in different murine tumor models: use of liposomal preparations.

Hexadecylphosphocholine (HPC) and its analogs with a longer alkyl chain (C18 and C20) were examined for antineoplastic activity in the murine tumor models P388 leukemia, B 16 melanoma, the mammary carcinoma C3H and Ca 755, and the human MT-1 mammary tumor in nude mice. The maximum tolerated doses were determined and found to be higher in mice than in rats. The toxicity of the alkylphosphocholines increases with chain length. The murine mammary carcinoma C3H and the human MT-1 mammary carcinoma showed response to HPC whereas the classical screening models did not respond to the synthetic lipids. Furthermore, HPC showed activity in a mitoxantrone-resistant P388 leukemia. Treated/control values between 120 and 160% in survival time could be obtained following a daily application of the lipid. Examination of the activity of possible cleavage products of HPC gave no information about the mechanism of action of the used etherlipids. Liposomes with encapsulated mitoxantrone, formed from alkylphosphocholines, cholesterol and dicetylphosphate had the same activity against P388 mouse leukemia as the free drug. The hemolytic activity of the three lipids tested in vivo was assumed to be related to toxic deaths of single animals; hemolytic activity was observed to be sometimes independent of schedule and dose.

Animals↗
PubMed1991

Pharmacokinetic behavior of [57Co]bleomycin liposomes in mice: comparison with the unencapsulated substance.

The distribution and excretion of [57Co]Bleomycin, dissolved in saline or encapsulated in liposomes, was studied in normal or tumor-bearing [P388 leukemia, reticulum cell sarcoma (RS)] mice. The free substance is cleared relatively quickly from the organism both after intravenous and intraperitoneal administration (t1/2 0.17 and 2.41 h, respectively), and is excreted predominantly via the urinary tract. In contrast, following entrapment in small unilamellar vesicles (SUV) or multilamellar vesicles (MLV), the 57Co radioactivity remains 7- to 30-fold longer in the blood stream and is detectable in considerable amounts in liver, spleen, lung and tumor of the RS model even after 48 h. Concomitantly, the renal excretion is diminished to about 50% of the free drug and the feces excretion is slightly increased, possibly due to the higher concentrations in the liver. Whereas the renal levels of radioactivity were similar with all application forms of [57Co]Bleomycin, there were marked differences in all the other tissues studied. After administration of SUV there was a higher activity in liver, brain and tumor, whereas MLV were more concentrated in spleen and lung. Therapeutic experiments confirmed the favorable results obtained with liposomes. While the free Bleomycin in the P388 leukemia had only a moderate influence on the lifetime of the animals with a treated/control value of 111%, encapsulation of the drug in SUV or MLV improved the results to 194 and 167%, respectively. In the intramuscular transplanted RS model, the SUV in a day 1 schedule had the same effect on tumor growth as the free drug in a day 1-4 schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Automated percutaneous lumbar discectomy with and without chymopapain pretreatment versus non-automated discoscopy-monitored percutaneous lumbar discectomy. An experimental study in human cadaver spines.

Percutaneous lumbar discectomy has gained growing interest during recent years as an alternative to open surgery for protrusions and non-sequestrated subligamentous intervertebral disc herniations. As a less invasive method it competes with chemonucleolysis. At least two modifications are known to date: automated percutaneous lumbar discectomy (APLD) with a 2-mm suction probe and non-automated, discoscopy-monitored percutaneous lumbar discectomy with a suction rongeur and a motor-driven shaver (NAPLD). In this study these two methods are compared for the amount of material extracted, dependence upon the degree of degeneration of the disc and intrinsic technical problems, using 20 human cadaver lumbar specimens for experimental testing. Total nucleotomy was not possible with either method. APLD yielded significantly less material and proved to be less effective in severely degenerated intervertebral discs than the NAPLD procedure, as preexisting gaps within the degenerated nucleus pulposus allowed the tissue to shift away from the tip of the 2-mm probe and facilitated displacement of the probe within the anulus fibrosus. By contrast, the rongeur, which first cuts the material to be removed and then carries it away by suction, was much more effective. Further data to support the advantages of non-automated percutaneous nucleotomy are discussed. Pretreatment of the disc with chymopapain did not result in a higher yield of nucleus material when combined with APLD.

Chymopapain↗
PubMed1990

Assessment of histogenesis and proliferative potential in cytologic specimens of human brain tumors. Value of immunocytochemistry and nucleolar organizer regions.

The value of immunocytochemistry and nucleolar organizer regions (NORs) for the histogenetic identification and the estimation of the proliferative potential of brain tumors was assessed by the investigation of imprint smears of 51 neurosurgical tumor specimens. A panel of five monoclonal antibodies was used to cover a broad range of immunohistochemical markers. For the assessment of NORs, a silver staining technique (AgNOR) was used. NORs were enumerated and measured by means of an interactive image analysis system. The immunocytochemical results were similar for the smears and paraffin-embedded sections for 95.6% of the investigations performed and for 76.2% of the cases. Glial fibrillary acidic protein (GFAP) was positive in 9 of 17 tumors of glial origin, but was negative in 9 metastatic tumors. Vimentin was positive in 10 of 10 and fibronectin in 9 of 10 meningiomas investigated. The number of NORs increased steadily with the increasing grade of malignancy. Especially in glioblastomas, the number of NORs per cell exhibited a wide range, which might reflect the heterogeneity of these neoplasms. Metastases revealed a higher number of NORs per cell than did glioblastomas. In the cytologic differential diagnosis of these tumors, an absence of GFAP expression combined with a high NOR count is suggestive of a metastatic tumor.

Adult↗
PubMed1990

Studies on sucrose-palmitate-stearate-containing vesicles encapsulating the cytostatic drug methylglyoxal-bis-guanyl-hydrazone.

Vesicles prepared from sucrose-palmitate-stearate and cholesterol encapsulating the anticancer drug methylglyoxal-bis-guanylhydrazone, were investigated. Treatment with drug-loaded vesicles of this composition in a q.d. 1-4 schedule resulted for murine leukemias P388 in nearly the same increase in life span as the corresponding dose of the free drug. Even very high dosages of sucrose-palmitase-stearate (up to 480 mg.kg-1.d-1) were tolerated by mice.

Animals↗
PubMed1990

[The concept of injury in radiotherapy from the point of view of the expert].

Starting from different definitions of the term "radiation injuries" published in literature considerations are made to term of injury in medicine generally and in radiotherapy particularly. It is suggested to use the term "radiogenic injury of health" instead of the term "radiation injury" and to speak of "complications in connection with medical application of rays" before causal explanation of the state of affairs.

Humans↗
PubMed1990

[Avoidable radiogenic damage to health as a result of radiotherapeutic measures].

Resulting from statements recorded in law directions of the GDR to the duty in profession of a physician and to restitution in injuries of health in consequence of breach of these duties experiences are reported that were collected with the report of complications in connection with medical use of radiation in almost 20 years. As a conclusion it is referred to data and discharge material that is necessary to reconstruct the irradiation. Report and quality criteria are specified exemplarily, that belong to a commentary to directives for reports num. 11 and, partly deduced from it, to directives for radiotherapy, came into force in 1986. Some casuistic contributions complete the representations.

Adult↗
PubMed1990

[Principles of selective decontamination from the radiobiological point of view].

Presented is the method of selective decontamination by van der Waaj. It is based on the conception of colonisation resistance deduced from animal experiments. So it means the concurrence of defense mechanisms which prevent the settlement of pathogenic germs and stabilize the normal microflora. First clinical and experimental results are reported.

Animals↗
PubMed1989

Cystic meningioma with unusual histopathological features.

A parasagittal meningioma of an eighty year old female patient showed by light and electron microscopy cystic architecture (forme humide) as well as nuclear vacuoles (indentations) and cytoplasmic inclusions. The latter are the known pseudopsammoma bodies or hyaline inclusions as demonstrated by light and electron microscopy. Light microcopy on paraffin sections and cytological smear preparations revealed, in addition to the cells of endotheliomatous meningioma and those containing the inclusions a third type with small granular cytoplasmic content. Electron microscopy showed characteristic features of meningioma such as folded double membranes, desmosomes and filaments and thus gave evidence of the meningiomatous nature of the tumor. By immunohistochemistry tumor cells in slightly focal distribution contained vimentin, whereas small clusters of cells with hyaline inclusions were strongly positive for cytokeratin. The dispersed cells of granular cytoplasmic content were positive for fibronectin. These findings, especially of the inclusion containing cytokeratin positive cell clusters may shed new light upon the concept of histogenesis and classification.

Aged↗
PubMed1989

[The state of and perspectives on liposome research].

Liposomes have been used for about 20 years in different fields of biological, medical and biophysical research, especially extensive for the encapsulation of pharmacologically active substances. In comparison with other drug carriers liposomes have some advantages, like variable productibility, biological degradability and relative toxicological and immunological safety. Despite these obvious advantages liposomes are not established pharmaceutical formulations, clinical trials are in the very beginning. In the submitted paper the up-to-date knowledge of liposome research with special emphasis of oncology is examined and future trends are derived.

Capsules↗
PubMed1987

Cytostatic activity of synthetic O-alkylglycerolipids.

A series of halogen-containing alkylglycerolipid analogs has been checked for their cytostatic activity both in vitro and in vivo. The compounds included alkyldeoxyhaloglycerols (I), alkyldeoxyhaloglycerophosphocholines (II), and alkyldeoxyhaloglycerophosphoric acids and alkyl esters (III). While compounds I and III were moderately active, compounds II were found to have a strong inhibitory effect on the proliferation of Ehrlich ascites tumor cells in vitro. Cell growth inhibition of 50% or more was found mainly in the late S- or G2-phase of the cell cycle as revealed by flow cytometry. Alkyl lysophospholipid analogs II and cholesterol form liposomes with high encapsulation efficiency and low permeability for entrapped substances. Compounds II were active against Lewis lung carcinoma in mice when applied in free form or as liposomes.

Animals↗
PubMed1987

Liposomes as carrier of methyl-GAG. Increased antitumor activity and reduced hypoglycemia in mice.

The encapsulation efficiency and the leakage on storage of various types of liposomes prepared from different lipid compositions containing the anticancer drug methyl-GAG (methylglyoxal-bis-guanylhydrazone) were investigated. Treatment with methyl-GAG in a q.d. 1-4 schedule resulted in the murine leukemias P 388 and L 1210 (i.v.) in nearly the same increase in life span as the corresponding dose in liposomes. In a q.d. 1, 3 schedule methyl-GAG containing liposomes revealed comparable effects as the 4-day treatment with the free drug. The hypoglycemic effect of 80 mg/kg methyl-GAG, q.d. 1-4, could be normalized when the drug was administered in reverse-phase evaporation vesicles. We conclude that the liposomal encapsulation of methyl-GAG leads to a depot effect with a slight relief of toxicity.

Animals↗
PubMed1987

Characterization of a new tumor in NMRI-mice suitable for chemotherapeutic experiments.

The tumor was found in the peritoneum of a 6-months old female NMRI-mouse. Histologically it can probably be classified as a less-differentiated reticulum-cell sarcoma (histiocytic sarcoma). Following ip. or sc. transplantation metastases were only in some cases found. After im. inoculation of tumor brei lungs, livers, kidneys, spleens and lymph nodes were free of metastases, as a bioassay revealed. The im. transplantation was the most suitable technique for chemotherapeutic experiments: It resulted in a 100% take rate and a relatively narrow and well reproducible death range; tumor size and life span of the animals could be used as therapeutic parameters. The tumor was highly sensible against the cytostatic drugs Cyclophosphamide, Doxorubicin and Vincristine. A moderate activity showed CCNU, Cis-DDP and Bleomycin, while DTIC and a novel Benzochinonguanylhydrazon-derivative only reversibly influenced the tumor growth and not the life time of the animals. Liposomally encapsulated Daunorubicin and Bleomycin had in general similar effectiveness as the drugs in its free form. Because of its high sensitivity against a lot of cytostatics with different mechanisms of action the tumor can be recommended for the screening of novel antineoplastic substances.

Animals↗
PubMed1986

[Combined therapy of tumors in adults].

A significant amelioration of treatment results is achieved by sequential chemotherapy and radiotherapy in patients with lymphogranulomatosis of stage IIb to IVb and in patients with non-Hodgkin's lymphomas in corresponding stages. Similar results will probably be obtained in patients with small cell bronchial carcinomas in a limited stage. Patients suffering from an initially inoperable ovarian cancer often reach an operable condition by sequential chemotherapy and radiotherapy. In the stages Dukes B2 and C of the rectum carcinoma, preoperative and/or postoperative irradiation significantly reduces the recurrence rates and increases the survival times. A considerable reduction of recurrence rates is obtained by postoperative radiotherapy in soft tissue sarcomas of the stages T1 to T3. Another improvement is anticipated by a neutron or neutron boost irradiation for stage T3 and by adjuvant chemotherapy for G3 tumors. In the osteosarcoma of adult persons, the results of the limb-sparing sequential therapy will not be worse than the results achieved by amputation. Retrospective analyses of the long-term results of radical mastectomy and conservative operation with postoperative irradiation in case of mammary carcinoma did not show any difference for the stages T1 to T3, N0 to N1.

Adult↗
PubMed1986

Effects of nifedipine on cell resistance and cardiac toxicity--in vitro and in vivo experiments.

Nifedipine can enhance the cytotoxicity of antineoplastic drugs. The present paper describes characteristics of sensitive and acquired resistant cells prior to and after transplantation into nude mice and experiments to reverse the acquired resistance to Daunorubicin (DR) by Nifedipine. Resistant cells (HT/DR+) are characterized by prolonged doubling time and diminished drug sensitivity and drug uptake. HT/DR+ cells show a slightly increased number of polyploid cells. These characteristics are not changed after nude mouse transplantation. Nifedipine enhances the intracellular level of Daunorubicin and cytotoxicity in vitro and in vivo in case of HT/DR+ cells. But Nifedipine acts both in vitro and in vivo also on sensitive cells (HT). This could support the hypothesis that Nifedipine increases the toxicity, which could be confirmed by experiments on mice (B6D2F1 strain). But probably the increased incidence of toxic deaths is not due to increased cardiac toxicity. This increase of toxicity could limit the clinical usefulness of the combination of antineoplastic drugs with calcium channel blockers.

Animals↗