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Biomedical subjects

K Tempel

Publications and source records attributed to K Tempel.

At least 19 recordsLinked to original sources
PubMed2001

A new class of drugs for BNCT? Borylated derivatives of ferrocenium compounds in animal experiments.

A new class of drugs, borylated derivatives of ferrocenium compounds, which show a comparatively facile synthesis is investigated on their boron neutron capture accumulation. Investigations focused on the fast and effective testing of 12 ferrocene derivatives with tetracoordinated boron atoms, which should accumulate in rodent tumors. The macroscopic studies on time-dependent boron distributions and boron concentrations in mice were carried out by inductively coupled plasma-atomic emission spectrometry, inductively coupled plasma-mass spectrometry, and quantitative neutron capture radiography. The determination of boron concentrations after injection of 2b showed high boron contents in spleen, liver, kidneys, less in lung and muscle, and poor in integral blood, blood plasma, tumor, and brain. It is interesting to note that 2b penetrates the blood-brain barrier which may be advantageous in the treatment of astrocytomas and glioblastomas.

Animals↗
PubMed1999

Mechanisms of bradykinin-induced catecholamine release in pithed spontaneously hypertensive rats.

Kinins have the potential to modulate the sympathetic system. However, the kinin receptor subtypes and secondary mediators involved in vivo are not fully characterized. Earlier studies failed to show complete inhibition by B1- or B2-antagonists of bradykinin-induced catecholamine release, and were impeded by direct stimulatory actions of those substances. Such effects may arise from the involvement of histamine, the release of which is known to be stimulated by bradykinin and kinin-receptor antagonists. The present study was designed to evaluate the significance of B2-receptors and histamine in the bradykinin-induced enhancement of plasma catecholamines in pithed spontaneously hypertensive rats. The effects of bradykinin, the B2-receptor antagonist HOE 140, histamine and the H1-receptor antagonist mepyramine were tested. Administration of histamine dose-dependently increased catecholamine release whereby a marked preference for adrenaline over noradrenaline was seen. The H1-receptor antagonist mepyramine (0.3 mg/kg) prevented this effect. Bradykinin (7.2 microg/kg) enhanced plasma adrenaline and noradrenaline. In doses > or = 10 microg/kg, HOE 140 completely suppressed the bradykinin-induced increase in plasma noradrenaline, while a slight stimulation of adrenaline that even persisted after a high dose of HOE 140 (100 microg/kg), was only abolished by additional administration of mepyramine (0.3 mg/kg). The H1-receptor antagonist at this dose did not influence the effectivity of bradykinin. It is concluded that the bradykinin-induced enhancement of catecholamine release during electrical stimulation is completely (noradrenaline) or predominantly (adrenaline) mediated by B2-receptors. A minor stimulating effect of bradykinin on plasma adrenaline is provoked independently of B2-receptors via histamine acting on H1-receptors.

Adrenergic beta-Antagonists↗
PubMed1999

New drugs for BNCT: an experimental approach.

New kinds of boron-containing drugs were developed and tested in several murine tumor models. The boron-containing ether lipid B-Et-11-OMe was injected in mammary carcinoma (AT17) and osteosarcoma (OTS-64) bearing mice. Furthermore boron-substituted ferrocenium derivatives were tested. Two were excessively toxic; the third could be investigated. Boron accumulation and time-dependent biodistribution were determined using alpha-particle sensitive films and inductively coupled plasma-atomic emission pectrometry (ICP-AES) and -mass spectrometry (ICP-MS) of tumors, organs and tissues. Additionally, a new method of boron detection by NMR is in preparation.

Animals↗
PubMed1999

Bleomycin-induced DNA damage and DNA repair in chicken embryo cells as compared to X-irradiation.

Following in vitro- and in ovo-exposure of chicken embryo cells, the level of bleomycin (BM)-induced damage was evaluated by using DNA synthesis, nucleoid sedimentation (SED), and viscometry of alkaline cell lysates (VISC). This damage was compared to X-irradiation, using 5.9-378 nM BM in vitro, 1.5-116 micrograms BM/egg in ovo, and 2-32 Gy, respectively, in vitro as well as in ovo. With respect to BM, the most notable result is the increase in DNA synthesis and VISC at the lowest concentrations of the drug. A decrease in both parameters was observed at high BM concentrations and following exposure to X-rays, concomitantly with an increase in SED. Regarding the radiomimetic drug BM and X-rays, different modes of DNA damage and DNA repair are suggested by previous investigations and the present results. Therefore, further evidence is presented, that the chicken embryo can act as a simple, rapid and inexpensive test system to characterize the biological effects of many nucleo- and/or cytotoxic agents.

Animals↗
PubMed1998

Interactions between the renin-angiotensin system (RAS) and the sympathetic system.

Angiotensin II is able to modulate both the presynaptic sympathetic system and the adrenal medulla resulting in an enhanced release of noradrenaline and adrenaline. Consequently, the inhibition of the converting enzyme by ACE inhibitors resulting in a lower concentration of angiotensin II or blockade of the specific AT1 receptors by AT1 receptor blocking agents should lead to a decrease in both noradrenaline and adrenaline release. It has been demonstrated that ACE inhibition did not influence the net catecholamine overflow during stimulation of the sympathetic nerves in contrast to AT1 antagonists which can specifically and dose dependently diminish noradrenaline and adrenaline release, an effect that could be explained by a compensating mechanism of bradykinin. Bradykinin may accumulate during ACE inhibition and is able to stimulate catecholamine release via B2 receptors. To verify the class effect of AT1 antagonists on presynaptic AT1 receptors, the AT1 antagonist candesartan was investigated regarding its presynaptic effect in pithed spontaneously hypertensive rats. As could be demonstrated with losartan and HR 720, candesartan lowered AT1 receptor mediated angiotensin II-induced noradrenaline release in a dose-dependent manner. It is concluded that AT1 antagonists inhibit angiotensin II mediated catecholamine release on presynaptic sympathetic nerves and the adrenal medulla at the specific AT1 receptor site. The effect can be described as a class effect of these imidazole derivatives.

Angiotensin II↗
PubMed1998

Transplacental transfer of radionuclides. A review.

Transplacental transfer of tritium (H), cesium (Cs), iodine (I), strontium (Sr) and plutonium (Pu) has been observed in all examined species with an active transfer mechanism for iodine, strontium and plutonium. Cesium and tritiated water freely cross the placenta and are distributed approximately uniformly in maternal as well as in fetal tissue. In pregnant mice, 137Cs concentrations in maternal organs were 4-6 times higher than in the foetus. With increasing weight, Cs amounts rise in the foetus. 131I distribution in the foetus before and after the beginning of thyroid function is totally different. In an 8-week-old human foetus, there was almost no accumulation of 131I in the thyroid gland, while on week 14 of gestation more than 40% of the fetal iodine was accumulated in the thyroid gland. Radioiodine given only once results in distinctly higher fetal-maternal ratios than after long-term exposure. Experiments performed to evaluate the extent of placental barrier of Sr in comparison to Ca showed a maximum of Sr/Ca discrimination early in pregnancy while at the end of pregnancy Sr and Ca are transported to almost equal proportions across the placenta. A well-known phenomenon is the accumulation of Pu in the yolk-sack of rats such that 80% of the total activity is contained in the feto-placental unit. For the extrapolation of results from animals to man, experiments should not be confined to laboratory animals but include primates. Furthermore, computer softwares like MIRDOSE could be used to simulate transplacental distribution.

Americium↗
PubMed1998

[Radiotherapy in veterinary medicine (review)].

A review of the latest literature concerning the present level of radiation therapy in veterinary medicine is given. In a general section physico-technical as well as biological fundamentals are discussed. In the special part of the paper indications for a radiation therapy of dogs, cats and horses are stated. In this respect the basis for a decision is the TNM-classification into different clinical stages according to the directions of the WHO. Tumors of the hemolymphatic system are very responsive to radiation therapy. While epithelial tumors are sensitive, tumors arising from the mesenchymal tissues react less sensitive. Melanoma and osteosarcoma seem to be resistant to radiation therapy. Besides this, radiation therapy is often questioned by the tolerance of the normal tissue.

Animals↗
PubMed1997

Oxygen tensions in rodent tumors after irradiation with neutrons.

We started investigations on intratumoral oxygen tension after irradiations with reactor fission neutrons using the Eppendorf-pO2 Histograph. Isotransplanted AT17-mammary carcinomas on C3H-mice and osteosarcomas OTS-64 on balb C-mice received 2 or 6 Gy neutrons single dose. Before and at certain points of time after treatment the pO2 values were evaluated. Some tumors with initially low median pO2 values showed a short-lasting increase between 2 and 24 h after irradiation. In those tumors with relatively high pretherapeutic pO2 values the pO2 decreased to the range of hypoxia. A third group of tumors showed no marked changes after irradiation. No tumor stopped growth during the observation period.

Animals↗
PubMed1997

[Chernobyl and its consequences--some veterinary medical points of view].

Summing up some recent publications, the author provides a survey about what happened, today's situation in Germany, the relation between food contamination and exposure, recommended generic intervention levels for foodstuffs, and possibilities to reduce contamination in food. Some agricultural counter-measures in the management of a post-accidental situation are especially taken into consideration. It follows that the veterinarian plays an important role in reducing population exposure by radioactive fall out.

Animal Feed↗
PubMed1997

[Influence of species of animal on radionuclide metabolism (review)].

With special regard to radiojodine, radiocesium and radiostrontium a review is given on comparative metabolism of some nuclides in various species. From data regarding exposure, absorption, distribution, retention and excretion of radionuclides species specific peculiarities are suggested which, in a fundamental manner, concern the toxicological evaluation of radionuclides as well as the possibilities of inter-specific extrapolation and the estimation of the transfer of radionuclides through the food chain.

Animals↗
PubMed1996

Oxygen tension in mouse mammary carcinomas and osteosarcomas after irradiation with reactor fission neutrons.

Investigations were made on intratumoral oxygen tension after irradiations with reactor fission neutrons using the Eppendorf-pO2-Histograph. Isotransplanted AT17-mammary carcinomas on C3H-mice and osteosarcomas OTS-64 on Balb c-mice received 2 or 6 Gy neutrons single dose. Before and at certain points of time after treatment the pO2-values were evaluated. Some tumors with initially low median pO2-values showed a short-lasting increase between 2 and 24 hours after irradiation. In the tumors with relatively high median pO2-values before irradiation the pO2 decreased to hypoxic range. A third group of tumors showed no significant changes after irradiation. None of the tumors stopped growth during the observation period.

Adenocarcinoma↗
PubMed1996

Formation and persistence of N7- and O6-methyl-guanine in DNA of chick embryo brain cells in ovo following administration of N-nitroso-N-methylurea.

Previously, O6-methyl-guanine-DNA alkyltransferase (AT) of the chicken embryo has been investigated in vitro. In the present studies, the effect of in vivo (in ovo) treatment with methylnitrosourea (MNU) was examined at a developmental stage of 15 days and doses of 1.25-20 mg/egg, yielding about 1-16 mmol MNU/kg embryo weight. At intervals of 1-24 h, DNA of the brain was prepared. N7-methylguanine and O6-methylguanine were quantified by combining a rapid method of DNA isolation, high-pressure-liquid-chromatography (HPLC) and electrochemical detection of the guanine-alkyl adducts. In parallel, the AT activity of brain homogenates was determined. Within the range of the detection limits (N7-methylguanine: 16 nM, O6-methylguanine: 2.5 nM), no repair of the guanine adducts, being about 500 nmol O6-methyl- and 1800 nmol N7-methyl-adducts per mmol guanine 1 h following administration of 10 mg MNU/egg, was evident. The rather low acute toxicity of MNU in the chicken embryo at the 15th day of development DL50/24 h being > 4 mg MNU/embryo, argues, therefore, for an additional repair mechanism, e.g. cell replacement repair.

Animals↗
PubMed1996

O6-alkylguanine-DNA alkyltransferase, DNase I, nucleic acid synthesis and nucleoids in vitro under the influence of pentosan polysulfate.

The in vitro influence of pentosan polysulfate (CAS 116001-96-8, PPS) on DNase I activity as well as on O6-alkylguanine-DNA alkyltransferase (AT), nucleic acid synthesis, nucleoid sedimentation and viscosity of alkaline lysates of chicken embryo brain cells was studied. PPS inhibited the activities of AT and DNase I in a dose-dependent manner, with ED50 values being about 13 and 380 micrograms/ml. Scheduled DNA synthesis was depleted by PPS. The ED50 values ranged between 45 and 55 micrograms PPS/ml. A slight increase in RNA synthesis could be observed at polyanion concentrations of 28-112 micrograms/ml. Nucleoid sedimentation and viscosity of alkaline cell lysates reflected a decrease in chromatin compactness at lower (7-25 micrograms/ml) and an increase in chromatin compactness at higher (> or approximately = 112 micrograms/ml) PPS concentrations. From the present results it is concluded that PPS, at clinically relevant concentrations, is able to interact in vitro with enzyme systems being critical to important nuclear functions. The remarkably high sensitivity of the nuclear enzyme AT deserves further investigations with regard to a possible synergism of polyanions and chemotherapeutically used alkylating agents.

Animals↗
PubMed1995

Adaptive response of the chicken embryo to low doses of x-irradiation.

Chicken embryos were x-irradiated in ovo with 5-30 cGy (=priming dose) at the 13th-15th day of development. After 3-48 h, brain- and liver-cell suspensions were x-irradiated in vitro with (challenge) doses of 4-32 Gy. Significantly less radiation damage was observed when the radiation response was measured by scheduled DNA synthesis, nucleoid sedimentation and viscosity of alkaline cell lysates 12-36 h after the priming exposure. In vivo, pre-irradiation with 10 cGy enhanced regeneration as evidenced by the DNA content of chicken embryo brain and liver 24 h following a challenge dose of 4 Gy. From nucleoid sedimentation analyses in brain and liver cells immediately after irradiation with 16 Gy and after a 30-min repair period in the presence of aphidicolin, dideoxythymidine and 3-aminobenzamide or in the absence of these DNA repair inhibitors, it is concluded that a reduction of the initial radiation damage is the dominant mechanism of the "radio-adaptive" response of the chicken embryo. Sedimentation of nucleoids from ethidium bromide (EB) (0.75-400 micrograms/ml)-treated cells suggests a higher tendency of "radio-adapted" cells to undergo positive DNA supercoiling in the presence of high EB concentrations.

Animals↗
PubMed1995

Radiation biochemistry of the chicken embryo: DNA synthesis and DNA degradation following X-irradiation.

Chicken embryos were X-irradiated with a dose of 8 Gy. At a developmental stage of 15 days, desoxyribonucleic acid (DNA) synthesis, nucleoid sedimentation, viscosity of the alkaline cell lysates and DNA fragmentation were examined in brain and/or liver cells. Further studies aimed at the appearance of acid-soluble nucleic acid metabolites in the allantoic fluid. Complementary investigations comprised the in vitro activities of a DNase I and a DNase II of liver and brain cells as well as of the allantoic fluid of X-irradiated embryos. It could be shown for the first time that, following acute X-irradiation of the chicken embryo, the inhibition of DNA synthesis is accompanied by at least two enzymatic DNA degradation phases. The early phase comprises a period of 6 (-12) h, whereas the second phase lasts, with organ-specific peculiarities, > or = 24 h. During the early period, some apoptotic phenomena are seen, whereas at the later stages of radiation response signs of necrolysis become evident. The excretion of DNA metabolites, probably oligonucleotides, in the allantoic fluid is enhanced following X-irradiation > 2 Gy and may be used as an additional parameter of the overall radiation damage. Therefore, the chicken embryo may be regarded as a radiobiological and possibly toxicological alternative to laboratory animals with respect to the nucleic acid metabolism.

Allantois↗
PubMed1994

The in vitro influence of sulfated bis-lactobionic acid amides on O6-alkylguanine-DNA alkyltransferase, DNase I, nucleic acid synthesis and chromatin structure.

The influence of four sulfated bis-lactobionic acid amides (BLAA) of molecular weights between 2388 and 2514 on O6-alkylguanine-DNA alkyltransferase (AT), DNase I and nucleic acid synthesis as well as on nucleoid sedimentation and the viscosity of alkaline lysates of chicken embryo cells was studied in vitro. The activities of AT and DNase I were inhibited by BLAA in a dose-dependent manner. Depending on the polyanion used, concentrations depleting AT activity by 50% ranged between 3.5 and 7.0 microM, whereas BLAA concentrations of almost 250-320 microM were needed to halve DNase I activity. At concentrations above 8 microM, BLAA decreased scheduled DNA synthesis in a dose-dependent fashion whereas RNA synthesis remained unchanged even at the highest BLAA concentrations used (2 mM). In chicken embryo brain cells BLAA exerted a biphasic effect on the nucleoid sedimentation and the viscosity of alkaline cell lysates reflecting a decrease in chromatin compactness at lower BLAA concentrations (10-100 microM) and an increase in chromatin compactness at higher polyanion concentrations (> or = 200 microM). The remarkably high sensitivity of the nuclear enzyme AT deserves further investigation in regard to the fate of the polyanions within cells and tissues.

Animals↗