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Biomedical subjects

B Hesse

Publications and source records attributed to B Hesse.

At least 127 records · Page 7Linked to original sources
PubMed1982

Effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and its nonpromoting analogue 4-O-methyl-TPA on dorsal dermal melanocytes of the Syrian golden hamster (Mesocricetus auratus).

The effect of the tumor promoter TPA and its inactive structural analogue 4-O-methyl-TPA on the induction of dorsal skin melanosis in the normal Syrian golden hamster and on the promotion of melanomas in DMBA-initiated animals was investigated. Both phenomena were observed in TPA-treated hamsters but could not be detected after exposure of animals to 4-O-methyl-TPA. In contrast to results obtained with a variety of other laboratory animals, neither TPA nor 4-O-methyl-TPA were able to induce epidermal hyperplasia of hamster dorsal skin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

7,12-Dimethylbenz[a]anthracene/12-O-tetradecanoyl-phorbol-13-acetate-mediated skin tumor initiation and promotion in male Sprague-Dawley rats.

In contrast to a previous report by Shubik and in accordance with a pilot study from our laboratory with female rats, the 2-stage skin carcinogenesis experiment could be successfully accomplished in male Sprague-Dawley rats. Male animals of this species are better suited for this long-term experiment since, under the conditions used, females are very sensitive to mammary gland tumor formation and show a drastically reduced survival time. A broad spectrum of tumors of epidermal origin could be induced by topical initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetra-decanoyl-phorbol-13-acetate (TPA) as promoter. The tumors were not only localized in the interfollicular epidermis but to a large extent also in the epidermal appendages. More importantly, the DMBA - TPA treatment led to the development of a variety of tumors of the connective tissue and the angiofibrous matrix. The incidence of these tumors was almost comparable to that found for epidermal tumors. In some animals we observed up to 12 histologically different tumors. Compared to the mouse, the tumor incidence in organs other than the skin was definitely lower. Ethyldiazoacetate (EDA), a substance which has been shown to induce skin tumors when administered i.v. to rats, was tested with regard to its initiating capacity. The combination EDA-TPA led to a skin tumor spectrum comparable to that produced by DMBA-TPA. However, the survival time of the EDA-TPA treated animals was significantly higher than those exposed to DMBA-TPA. EDA, therefore, seems to be a suitable alternative to DMBA for systemic initiation of skin tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Tumor initiation by 7,12-dimethylbenz[a]anthracene in dermal melanocytes of hamster: inhibition through 7,8-benzoflavone.

Initiation of dermal melanocytes by 7,12-dimethylbenz[a]-anthracene (DMBA) in the dorsal skin of Syrian golden hamsters was investigated for its sensitivity to inhibition by 7,8-benzoflavone (BF). Initiation was carried out by a single intragastric application of DMBA (50 mg/kg body weight) and melanoma development pursued with or without subsequent promotion through repeated topical administration of 12-O-tetradecanoylphorbol-13-acetate (40 nmol/animal, 3 X weekly). A single intragastric application of BF (200 mg/kg body weight) 2 h prior to DMBA resulted in a suppression of melanoma yields by approximately 70%. Further, there were indications that BF generally causes a decrease of melanoma rates and an increase of survival rates. The study provides a first mechanistic concept for melanoma initiation by DMBA. It shows that metabolic activation of DMBA (i) is prerequisite to initiation and (ii) has a similar molecular basis as in other target cells of DMBA, the essential pathway including the cytochrome P-448-dependent monooxygenase system.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Treatment of diabetic orthostatic hypotension with pindolol.

The hemodynamic variables, plasma noradrenaline and plasma renin concentrations were studied in a 57-year-old female with insulin-dependent diabetes of long-standing and orthostatic hypotension. For 6 months she had been bedridden because of severe orthostatic symptoms. Reflex responses in the heart rate and blood pressure during the Valsalva manoeuvre as well as beat-to-beat variations in heart rate were absent. Plasma noradrenaline concentrations were subnormal both in the supine and upright positions. After treatment with Pindolol 15 mg/day the patient was able to walk around and lead an almost normal life. The orthostatic symptoms recurred after withdrawal of therapy and disappeared on resumption of therapy. Arterial blood pressure measured intra-arterially decreased less in the up-right position during treatment with pindolol compared to that in the untreated condition. The heart rate did not change during treatment with Pindolol. Our findings suggest that Pindolol may be an important drug in the treatment of diabetic orthostatic hypotension.

Autonomic Nervous System Diseases↗
PubMed1981

Lack of adrenergic influence on renin release after furosemide in normal man.

The role of the sympathetic nervous system in furosemide-induced renin release was investigated in six normal subjects. After intravenous administration of furosemide, plasma renin concentrations increased more than two-fold within 15 min. Neither replacement of urinary fluid loss by intravenous infusion of saline nor pharmacological beta-blockade with d,1-propranolol changed the renin response to furosemide. The activity of the sympathetic nervous system, as estimated by measurement of plasma catecholamine concentrations, remained at the reference level after furosemide. It is concluded that the sympathetic nervous system is not involved in renin release after intravenous administration of furosemide.

Adult↗
PubMed1981

Diaplacental initiation of NMRI mice with 7,12-dimethylbenz[a]anthracene during gestation days 6--20 and postnatal treatment of the F1-generation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate: tumor incidence in organs other than the skin.

The tumor spectrum and tumor incidence in organs other than the skin were investigated in the 12-O-tetradecanoylphorbol-13-acetate (TPA) treated F 1-generation of 13 groups of NMRI mice which had been initiated by a single intragastric dose of 7,12-dimethylbenz[a]anthracene during days 6, 8, and 10--20 of pregnancy. Promotion by topical application of TPA to the back skin was carried out twice per week 12 weeks after birth over a period of 26 weeks. The forestomach epithelium represented the only organ in which statistically significant 2-stage carcinogenesis could be demonstrated. A promotion effect could be seen in tumors of the Harderian gland, of the liver of male animals and on the development of both benign and malignant tumors of the lung in both sexes. Promotion treatment therefore led to an activation of initiated tumor cells in those organs in which a very sensitive, more or less narrowly spaced oncogenic determination period exists.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Reduced norepinephrine response to dynamic exercise in human subjects during O2 breathing.

The purpose of this investigation was to study the influence of hyperoxia on catecholamine response to dynamic exercise. While breathing either 21 or 100% O2 seven subjects performed submaximal bicycle exercise. Arterial blood pressure was similar in both exercise experiments. The CO2 output was not influenced by 100% O2 breathing, but increments in plasma lactate concentration were reduced. The increases in plasma norepinephrine and epinephrine concentrations and heart rate were significantly lower during 100% O2 than during 21% O2 breathing. The results suggest that O2 plays an important role in the regulation of sympathetic nervous activity during dynamic exercise in humans.

Adult↗
PubMed1980

Two-stage skin carcinogenesis by systemic initiation of pregnant mice with 7,12-dimethylbenz(a)anthracene during gestation days 6-20 and postnatal promotion of the F 1-generation with the phorbol ester 12-tetradecanoylphorbol-13-acetate.

The DMBA-TPA-mediated two-stage skin carcinogenesis experiment was modified in that pregnant mice were systemically treated once during pregnancy with the carcinogen. Intragastric application times were fetal days 6, 8, and 10-20. A control group of pregnant mice received repeated doses (from days 8-20) of sesame oil, which was used as a solvent for DMBA. At the age of 12 weeks, the offspring of the control group were divided into two groups, one of which was left completely untreated, the other received TPA applications over 26 weeks. The 12-week old F 1-progeny of each transplacentally initiated group was also divided into subgroups, which either received no further treatment (subgroups A) or were promoted with TPA (subgroups B). Neither the F 1-animals of the two control groups nor that of the transplacentally initiated but postnatally not promoted subgroups 6 A-20 A developed skin tumors. The same holds true for the TPA-promoted offsprings of mother animals which had received DMBA at days 6 and 8 of gestation. Skin tumor development after TPA promotion was first observed in animals of subgroup 10 B. Thereafter, tumor rates and tumor yields increased and latency periods decreased progressively in the B-subgroups with the postponement of initiation to later fetal periods. Day 19 of prenatal development proved to be the most sensitive period to transplacental initiation, whereas initiation at day 20 led to a significant decrease in tumor rate and yield. The capability to initiate skin tumors and the extent of initiation can be correlated to both the organogenesis of the epidermis and its proliferative rate in utero.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1980

Tumor inhibition by metallocenes: antitumor activity of titanocene dihalides (C5H5)2TiX2 (X=F, Cl, Br, I, NCS) and their application in buffered solutions as a method for suppressing drug-induced side effects.

The antitumor activity of titanocene dihalides (C5H5)2TiX2 with X=F, Cl, Br, I, NCS is investigated against Ehrlich ascites tumor in CF 1 mice. Varying doses of the compounds are applied as single i.p. injections 24 h p.t.t. both in non-buffered (pH 1.4-3.9) and buffered (pH 4.2-5.9) solutions or suspensions, all of the substances achieving in optimum doses cure rates of 100% on day 120 p.t.t. This corresponds to I.L.S. values of 600-750% referred to the untreated controls. Some drug-induced side effects, especially the appearance of postperitonitic symptoms several weeks after i.p. application of higher doses of titanocene dihalides, are strikingly reduced by pH elevation in the injected drug solutions.

Animals↗
PubMed1980

[Tumor inhibition by metallocenes: effect of titanocene, zirconocene, and hafnocene dichlorides on Ehrlich ascites tumor in mice (author's transl)].

The antitumor activity of the metallocene dichlorides TDC, ZDC, and HDC against Ehrlich ascites tumor in CF1 mice is investigated. A single i.p. injection of TDC in the optimum dose (30-60 mg/kg) 24 h p.t.t. achieves survival of 80-90% of the animals until day 180 p.t.t. without any tumor manifestation. This indicates an increase in the mean survival time of about 900% referred to the untreated animals. In contrast, ZDC and HDC exhibit no recognizable antineoplastic properties under equal experimental conditions. Assuming a similar mechanism of tumor inhibition for both DDP and the antineoplastic active metallocene dichlorides TDC, VDC, and MDC the comparatively increased non bonding Cl...Cl distance ("bite") of ZDC and HDC may be responsible for cancerostatic inactivity of the latter compounds.

Animals↗
PubMed1980

Two-stage carcinogenesis in NMRI mice: intravaginal application of 7,12-dimethylbenz[a]anthracene as initiator followed by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate as promoter.

In this study a new modification of the systemic 2-stage carcinogenesis experiment is described. Tumors were induced in NMRI-mice using a single intravaginal application of the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) (initiator) followed by intravaginal treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) (promotor) as a cocarcinogen over a period of 52 weeks. The substances were applied using small tampons. Development of preneoplastic lesions or neoplasias was not found in the group of untreated control animals (n = 50) and in TPA treated animals (n = 50). However, mice which had been treated with TPA alone showed pronounced hyperplasia. When DMBA was applied without subsequent treatment with TPA (n = 100), formation of preneoplastic lesions was frequently observed. Fibroepitheliomas (papillomas), carcinomas and sarcomas, typically located intravaginally and at the external region of the vagina, were observed after the combined treatment with DMBA and TPA (n = 100). In addition, benign as well as malignant tumors were found, mainly in the forestomach, in DMBA treated animals and more frequently after application of DMBA and TPA. Tumors of the lung and leukemias were identified more frequently in comparison to the normal spontaneous tumor rate in NMRI mice, and were probably in part caused by the promoting substance TPA. On the other hand, no significant tumor formation in the mammary gland and in the ovaries was observed after DMBA/TPA application. The tumors observed in these organs were, however, caused by treatment with the carcinogen DMBA only. This new modification of the 2-stage experiment, i.e. the direct intravaginal application of initiating and promoting substances, has special relevance for the elucidation of the mechanisms involved in the development of carcinomas located at the portio vaginalis uteri in humans.

9,10-Dimethyl-1,2-benzanthracene↗