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Biomedical subjects

J Pohl

Publications and source records attributed to J Pohl.

At least 181 records · Page 10Linked to original sources
PubMed1982

Studies on the urotoxicity of oxazaphosphorine cytostatics and its prevention--III. Profile of action of sodium 2-mercaptoethane sulfonate (mesna).

Mesna is a pharmacologically unremarkable, physiologically largely inert and almost totally non-toxic thio compound. It is rapidly eliminated renally and only slightly permeates into tissues. It has been shown experimentally that the bladder damage inducible in the rat by administration of oxazaphosphorine cytostatics can be successfully prevented by quite small doses of mesna. The detoxifying action of mesna is limited to the kidneys and the efferent urinary tract. The systemic effects of the oxazaphosphorines, however, remain unaffected. This applies particularly to the curative oncocidal efficacy of these compounds. It has also been shown experimentally that mesna does not affect the curative effects of other cytostatic drugs (doxorubicin, BCNU, methotrexate, vincristine). The efficacy of the cardiac glycoside proscillaridin is also not impaired by mesna.

Animals↗
PubMed1981

Growth regulation of fibroblasts by thrombin, factor XIII and fibronectin.

The stimulation of fibroblast proliferation by thrombin and factor XIII is accompanied by an intracellular increase of cGMP. In contrast fibronectin inhibits the 3H-thymidine uptake of fibroblasts. Pre-treatment of fibroblasts with neuraminidase eliminates the stimulating effect of thrombin completely and induces a shift of the optimum stimulating effect of factor XIII to higher concentrations. It is discussed that thrombin and factor XIII stimulate the proliferation of fibroblasts as growth hormones and regulate in combination with the inhibiting fibronectin the growth of fibroblasts in thrombus organization, wound healing and in the arteriosclerotic vessel wall process.

Animals↗
PubMed1981

Detoxification of urotoxic oxazaphosphorines by sulfhydryl compounds.

Urotoxic side effects, especially hemorrhagic cystitis, have so far been a limiting factor in the therapeutic use of cyclophosphamide (Endoxan), ifosfamide (Holoxan), and trofosfamide (Ixoten). The uroprotective agent mesna (Uromitexan) allows regional detoxification in the kidney and the urinary tract, and thus clinical prevention of the urotoxic side effects of the above cytostatics. The uroprotective mechanism of mesna is based on the formation of nontoxic additive compounds with acrolein and 4-hydroxy-metabolites. In the body, mesna is rapidly transformed into its biologically inert disulfide. After glomerular filtration mesna disulfide is rapidly reduced by reacting with the glutathion system and elimination in the urine as a free thiol compound, further detoxifying the aggressive oxazaphosphorine metabolites.

Animals↗
PubMed1981

[Absolute emission spectra of commonly used UV-tubes].

In this study the problem of absolute energy spectra of commercially available UV light sources was investigated. The absolute intensity of emitted light produced by two UV lamps (Waldmann and Wolff) was determined by means of narrow band UV light interference filters in combination with a research photometer calibrated according to a tungsten band lamp. The intensity of UV-A emitted by Waldmann lamps in a PUVA 4000 irradiation box was 5.5 mW/cm2. The emission of UV-B (280-320 nm) was 0.6% of the total energy. In contrast, the UV lamps provided by Wolff emitted 2.1% UV-B. The importance of exact determination of UV-B light emitted by commercial UV light sources is emphasized.

PUVA Therapy↗
PubMed1980

Photoinactivation and recovery in skin fibroblasts after formation of mono- and bifunctional adducts by furocoumarins-plus-UVA.

Cultured skin fibroblasts from young male guinea pigs were irradiated with UVA light in the presence of 8-methoxypsoralen (8-MOP) or angelicin. As compared to 8-MOP 30 times higher concentrations of angelicin were needed to obtain comparative inhibition rates of DNA-synthesis. Complete cellular recovery could be observed when the cell cultures were treated with angelicin-plus-UVA (320-400 nm) or 8-MOP-plus-395 nm. Both treatment schedules are known to cause monofunctional photoreactions. In contrast to this, bifunctional photoreactions caused by 8-MOP-plus-365 nm produced an inhibition of DNA synthesis which lasted more than four days. Also, UVA (320-400 nm) applied to cells treated with 3H-labeled 8-MOP resulted in a dose-dependent binding of 8-MOP molecules again lasting several days. Application of 8-MOP-plus-UVA (320-400 nm) to cells growing in log-phase showed a characteristic change in morphology. An increasing number of polynuclear and hyperchromatic cells appeared with time after treatment. In this subpopulation of cells DNA synthesis continued without division as revealed by DNA measurements and autoradiography. It is concluded that monofunctional adducts caused by angelicin-plus-UVA as well as 8-MOP-plus-395 nm permit cellular recovery whereas bifunctional photoadducts remained without recovery. In the latter case semiconservative DNA synthesis continued leading to hyperchromatic cells which could serve as a parameter for the presence of cross-linked nuclear DNA strands.

Animals↗
PubMed1979

Thrombin and fibrin-induced growth of fibroblasts: role in wound repair and thrombus organization.

Skin fibroblast cultures were treated with various components of the blood clotting system (thrombin, fibrinogen and fibrin) during the logarithmic growth phase. Fibrin as well as thrombin showed dose-dependent growth promoting activities as revealed by cell counting and 3H-thymidine uptake. No effect was seen with fibrinogen. After entrapping in polymerizing fibrin enriched by complete culture medium the cells elongated, multiplied and formed net-like interconnecting cell strands throughout the clots. Nutritional deprivation appeared as a limiting factor for eventual growth cessation. The results demonstrate active growth of fibroblasts in fibrin clots such as present in healing wounds and thrombi. The production of thrombin by the coagulation cascade does not only result in the conversion of fibrinogen to fibrin but has also a long-lasting hormone-like effect on fibroblast proliferation which is of essential importance in wound healing, thrombus organization and progression of chronic atherosclerotic lesions.

Animals↗
PubMed1979

Dose-effects of 8-methoxypsoralen and long wave UV-light in 3T3 cells: evaluation of phototoxic index.

3T3 cells were cultured until confluency and treated with various doses of 8-methoxypsoralen followed by long wave UV light irradiation. The inhibition of 3H-thymidine incorporation was dose-dependent for both, psoralen and light. A phototoxic index (PTI) was established demonstrating that a constant correlation between psoralen and UVA light exists for the photoinactivation in living cells.

Animals↗
PubMed1979

Growth characteristics of skin fibroblasts and 3T3 cells entrapped by polymerizing fibrin.

Skin fibroblasts as well as 3T3 cells were cultured after entrapping freshly prepared cells in medium containing polymerizing fibrin. In contrast to cells grown on plastic substratum, fibrin-clot-cultured cells became highly elongated forming strands of cells. The strands interconnected by lateral cellular protrusions so that horizontal networks of cells were present throughout the clots. Cell growth as well as stretching were dependent upon the concentrations of fibrin. Highest growth rates were obtained with low fibrin concentrations (0.3 mg fibrinogen per ml). As shown by deprivation experiments nutritional limitations appear to be responsible for differences in growth rates observed in fibrin clots of higher density. In this system the fibrin meshwork serves as substratum for adhesion, elongation and multiplication of fibroblasts. The method makes it possible to study single cells in culture and the effects of persistent microenvironmental influences.

Animals↗
PubMed1979

Photoinactivation of skin fibroblasts by fractionated treatment with 8-methoxypsoralen and UVA.

Guinea pig skin fibroblasts treated with low doses of 8-methoxypsoralen (8-MOP) and long-wave ultraviolet light (UVA) showed a dose-dependent inhibition of 3H-Thymidine incorporation as determined by liquid scintillation counting. The minimum incubation time necessary to obtain constant inhibition rates was 60 min. By washing the drug was removed from the reactive sites within 30 min. Repeated light exposure at a constant concentration of 8-MOP caused a cumulative inhibition of DNA synthesis. Irradiation of 8-MOP-plus-UVA treated cells, from which the drug was removed, produced a small increase in photoinhibition. Split dose treatment at various time intervals (ranging from 1--48 hr) revealed inhibitory rates, which correspond to the total amount of UVA applied. No recovery effects were seen in cultures treated by single or multiple applications of 8-MOP-plus-UVA.

Animals↗
PubMed1979

The clinic as an interpersonal field of dynamic psychiatric treatment of psychosomatic diseases.

In Günther Ammon's structural personality model, psychosomatic illnesses are understood to be the expression of a structural ego-defect--especially in the central ego-function of the body-ego, of identity and of constructive aggression--which owes its origin to an insufficient mother-child symbiosis. The dynamic psychiatric clinic realises an interpersonal field, into which the defects are externalised and remedied by the process of a late ego development. The clinic offers various therapeutical levels: the clinic as a whole, the analytical milieu, group and individual therapy, whereby working-through of the interdependence of patient and staff dynamics has a main integrating function.

Aggression↗
PubMed1979

Acrolein, the causative factor of urotoxic side-effects of cyclophosphamide, ifosfamide, trofosfamide and sufosfamide.

The urotoxicity of oxazaphosphorine cytostatics is not based on their alkylating activity but on the presence of acrolein, which is spontaneously formed in the urine from the primary metabolites eliminated via the kidneys. Thus, acrolein proved to be the causative factor in the urotoxicity of oxazaphosphorines. The mechanism of action of the uroprotector sodium 2-mercaptoethane-sulfonate (mesnum, Mitexan) is mainly based on the formation of a non-toxic additive compound with acrolein.

Acrolein↗
PubMed1978

Photoinactivation of cultured skin fibroblasts by sublethal doses of 8-methoxypsoralen and long wave ultraviolet light.

Cultured guinea pig skin fibroblasts were treated with 8-methoxypsoralen (8-MOP) and UVA light. Determination of 3H-TdR-uptake as well as counting of the number of adherent cells was carried out 24 hr later. Incubation of fibroblasts with varying concentrations of 8-MOP (10(-4) to 10 microgram/ml) or 1 to 5 J/cm2 UVA alone showed no effect. When 8-MOP-photosensitization was followed by UVA a dose response was observed. This ranged over 3 orders of magnitude of the concentration of 8-MOP. Changes in irradiation energy produced a higher inhibition of 3H-TdR incorporation as compared to changes in 8-MOP concentrations. Using the same energy of UVA changes in which 3H-TdR uptake was inhibited by 50% showed no loss of plating activity. A fraction of these cells underwent DNA synthesis and division after reseeding. The results indicate that under the dose regimens currently used for the treatment of various skin disorders a proportion of the cells may become sublethally photoinactivated to undergo division. When reseeded these cells still are able to perform cellular functions such as spreading and attachment.

Animals↗