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F H Kemper

Publications and source records attributed to F H Kemper.

At least 19 recordsLinked to original sources

[Planning, realization and evaluation of post-marketing surveillance studies. Recommendations of the Society for Phytotherapy].

Post-marketing-surveillance studies with herbal drugs usually are prospective prescription-epidemiological studies, which should allow statements on quality, efficacy and safety. Until now neither laws nor concrete normative guidelines for the methodology and the evaluation of post-marketing-surveillance studies are existing which could be used for pharmacovigilance. In the present paper guidelines for planning, realisation and evaluation are presented which should allow studies of high quality. The essential components required for the investigational plan are focussed. Also recommendations on the obligatory, optional and special components of the study protocols are made. Additionally statistical methods which allow the evaluation of the therapeutic efficacy are presented.

Humans↗

Analysis of the components of Lycopus europaeus L. in body fluids during metabolism studies. Comparison of capillary electrophoresis and high-performance liquid chromatography.

During pharmacokinetic studies with extracts obtained from medicinally used plants, analysis in body fluids is mainly performed by HPLC, an established separation method. In this paper high-performance capillary electrophoresis (HPCE) is investigated for its ability to separate such complex extracts. Crude extracts of Lycopus europaeus L. (Lamiaceae) are traditionally used against mild forms of hyperthyroidism. The metabolism of a 70% ethanolic extract with respect to some of its individual main components (rosmarinic and caffeic acid, luteolin-7-glucoside) and a mixture of the pure compounds were investigated using isolated perfused rat liver. After solid-phase extraction metabolites were determined using HPCE and HPLC separation techniques. A buffer solution composed of 0.05 mol l-1 Na2HPO4 at pH 7.0 with 30% acetonitrile was found to be the most suitable electrolyte for HPCE separation. The best mobile phase for isocratic HPLC was 0.03% TFA-acetonitrile (82:18, v/v). Data obtained with HPCE are in good accordance with those from HPLC; HPCE, however, is clearly more rapid and simple to perform.

Animals↗

The effect of Chelidonium majus herb extract on choleresis in the isolated perfused rat liver.

The total ethanolic extract, the phenolic and the alkaloidal fraction of the herb of Chelidonium majus L. (Papaveraceae) were tested for their choleretic activity using the isolated perfused rat liver. The total extract significantly caused chloresis by increasing the bile acid independent flow (BAIF); the observed weak activity of both fractions, tested each and as combination, however, was not significant.

Animals↗

Endocrine effects of Lycopus europaeus L. following oral application.

Lycopus extracts are used in folk medicine for the treatment of hyperthyroid symptoms. Diverse effects on the pituitary thyroidal system as well as on the pituitary gonadal system could be confirmed in experimental studies. But till now endocrine effects of Lycopus extracts in experimental animals were observed after parenteral application only. Therefore in this investigation an ethanolic extract of Lycopus europaeus was applied orally to rats, diverse endocrine parameters were measured between 3 and 24 h later and the effects compared to an i.p. treated group. The plant extract given p.o. caused a long lasting (for a period of more than 24 h) decrease of T3 levels, presumably as a consequence of a reduced peripheral T4 deiodination. A pronounced reduction of T4 and thyroid stimulating hormone (TSH) concentrations was observed 24 h after application of the test solution by gavage. The luteinizing hormone (LH) decrease as well as the TSH decrease, which was pronounced in spite of reduced T4 and T3 levels indicate a central point of attack of the plant extract. Differences in the biological activity in dependence on the route of application may be explained e.g. by differences in absorption of plant constituents.

Animals↗

Human organ specimen banking--15 years of experience.

As a reaction to the lack of information concerning ranges of a 'normal xenobiotic burden' within the population and also the aquatic, terrestrial and atmospheric environments, the sampling and storage of environmental materials in Germany in 1974 as a possible tool for environmental observation and early recognizing of hazards was proposed. During subsequent years the collection of human specimens was undertaken in Münster. In a pilot phase (1978-1983) conditions of optimized storage were investigated, including reliable storage temperature and container materials. Since 1985 the Environmental Specimen Bank for Human Tissue in Münster has been institutionalized under the auspices of the Federal Ministry of Environment, Nature Protection and Nuclear Safety as well as the Federal Environmental Agency in Berlin. Up to 1991 about 300,000 samples had been collected and stored at -85 degrees C in a walk-in deep-freezer of 34 m3 comprising autopsy material as well as 'available' organs form living persons (e.g. blood, urine, hair, human milk, saliva, seminal plasma, sweat). Having fulfilled the tasks within the scope of environmental banking the Münster institution has proved to be an adequate scientific tool. It has been integrated into the logistic system of the Environmental Specimen Bank in Germany having the following main tasks (a) the development of Standard Operation Procedures (SOP) for sampling and sample handling, (b) evaluation of reliable analytical methods for inorganic and organic sample characterization, (c) collection of a sufficient data pool for reference ranges of xenobiotics, which are essential for environmental risk assessment, and (d) the evaluation of the efficacy of legislative xenobiotic restrictions: this could be proved for lead and some organochlorine pesticides.

Adipose Tissue↗

Environmental specimen banking and poisons control--a new challenge.

Today clinical toxicology and poisons control are widely lacking objective criteria, e.g., analytical data, figures of kinetics and metabolism in acute and chronic poisoning. Co-operation between clinical toxicology and an environmental specimen bank for human tissue will help to overcome many difficulties and complement one another. The possible power of such a co-operation is demonstrated by the example of the institutions in Münster, Germany. The successful strategies used for setting-up an environmental specimen bank for human tissue may also be applied in clinical toxicology and experimental toxicology. The frame of a university medical clinic seems to be the ideal basis of an effective co-operation of an Environmental Specimen Bank for Human Tissue, a Poisons Control Centre and clinical toxicology. In general a co-operation of an environmental specimen bank for human tissue and a poisons control centre will be cost-saving and beneficial to both and an environmental specimen bank for human tissue will gain the status of a unique tool for risk assessment of xenobiotics.

Animals↗

Influence of 3,5-dimethyl-3'-isopropyl-L-thyronine on thyroid state and gestational outcome in the Wistar rat.

3,5-Dimethyl-3'-isopropyl-L-thyronine (DIMIT, CAS 26384-44-1), a non-halogenated, artificial analogue of the thyroid hormone T3, was administered once daily by intragastric gavage to pregnant Wistar rats on days 17-20 of gestation to elucidate the effects of DIMIT on maternal and foetal thyroid state and gestational outcome under the influence of low iodine or iodine excess nutrition. Doses of 20 micrograms.kg-1.d-1 and 150 micrograms.kg-1.d-1 DIMIT were applied. Throughout pregnancy the animals were kept on low iodine diet and either on iodine free drinking water or iodine excess. There was no statistically significant effect on maternal body weight, weight of living foetus, the rate of intra-uterine death before day 16 of gestation, water and food consumption, and no hint of maternal thyrotoxicosis. The vital off-spring did not reveal any signs of gross malformation. DIMIT decreased serum TSH both in dams and foetus, and diminished the TSH stock of the pituitary gland of the dams. T3-levels were also lowered in maternal serum by DIMIT. These DIMIT induced effects were observed irrespective of iodine deficiency or excess. There was no difference in foetal mortality before onset of DIMIT-treatment, but the gestational death rate increased in a dose-related manner by the administration of DIMIT. This serious adverse effect became apparent at a DIMIT-dose that is not sufficient for a complete compensation of foetal hypothyroidism in utero. The higher prenatal mortality was accompanied by a decreased placental weight, but not by a reduced body weight of surviving foetus.

Animals↗

Embryotoxicity study of propenoic acid, 3-(4-methoxyphenyl)-3-methylbutylester in the Wistar rat.

3-(4-methoxyphenyl)-3-methylbutylester, propenoic acid (MPMBE; CAS no. 71617-10-2), a UVB-light filter used for sun protection of the skin, was administered once daily by intragastric gavage to pregnant Wistar rats on days 6-15 of gestation. Doses of 0.25 ml/kg/day (study group: D0.25), 0.75 ml/kg/day (D0.75) and 2.25 ml MPMBE/kg/day (D2.25) were applied. A positive control group (Pos) received 15 mg (all trans) retinoic acid/kg/day. MPMBE revealed some toxic effects in the dams of the group receiving the highest dose (D2.25): marked loss of body weight, polydipsia, reduced food consumption and intensified loss and thinning of hair. Only thinning or partial loss of hair without any other harmful effects was seen in the dams of group D0.75. An increase in embryonic deaths was striking in group D2.25; the living foetuses revealed signs of retarded development, but no major external or internal anomalies as signs of teratogenicity. This study was not able to present any teratogenic effects induced by MPMBE in the offspring, even at very high oral doses (> 2 g/kg/day) that caused substantial toxicity in the dams. In conclusion, concerning embryotoxicity an oral dose of 250 mg/kg/day MPMBE is regarded as a safe no-observed-effect level, whereas even 750 mg/kg/day MPMBE--following acknowledged rules--can be judged as a borderline no-observed-adverse-effect level.

Alopecia↗

Metabolism of garlic constituents in the isolated perfused rat liver.

The metabolic and kinetic behaviour of different garlic (Allium sativum L., Alliaceae) constituents were investigated in the isolated perfused rat liver, using aqueous extracts of garlic powder as well as isolated allicin, the main product of the enzymatic degradation of alliin. Allicin (allyl thiosulfinate) showed a remarkable first pass effect and passed the liver unmetabolized only at high concentrations which caused considerable cell injuries. Diallyl disulfide and allyl mercaptan were identified as metabolites of allicin, whereby diallyl disulfide probably is the metabolic precursor of allyl mercaptan as shown by perfusion with diallyl disulfide alone. The metabolites diallyl disulfide and allyl mercaptan could be determined in the perfusion medium as well as in the bile and the liver tissue. Other degradation products of garlic were also investigated in this model. Ajoenes and vinyldithiins were detected in perfusion medium after liver passage but no metabolites of them could be identified up to now.

Animals↗

Structures of compounds with antigonadotropic activity obtained by in vitro oxidation of caffeic acid.

Two new cyclolignan derivatives were isolated by HPLC from the mixture of substances obtained after oxidation of caffeic acid with KMnO4. Their structures were elucidated by spectroscopic methods as 2,3-dicarboxy-6,7-dihydroxy-1-(3', 4'-dihydroxy)-phenyl-1, 2-dihydronaphthalene (1) and 3-carboxy-6,7-dihydroxy-1-(3', 4'-dihydroxy)-phenylnaphthalene (2). Compounds 1 and 2 exhibit antigonadotropic activity as do the extracts of crude drugs of Lycopus europaeus and Lithospermum officinale after oxidation by plant enzymes.

Animals↗

Hexachlorobenzene content in human whole blood and adipose tissue: experiences in environmental specimen banking.

By making use of material held in the Environmental Specimen Bank for Human Tissue Muenster (University of Münster, FRG), up to 11 organochlorine pesticides were analysed in organs (whole blood and adipose tissue) of living people, using real-time monitoring, and in autopsy material (up to 35 organs). The hexachlorobenzene (HCB) contents in whole blood samples of two comparable 'normal' populations (age 20-30 years, n = 118 and 125) were: median 2.30 micrograms/l, range 0.05-13.5 micrograms/l in 1977 and median 3.55 micrograms/l, range 0.94-16.3 micrograms/l in 1982. Females showed a slightly higher range than males. A pesticide-exposed group of wine growers (n = 122) showed a range of 0.86-29.6 micrograms/l with a median of 7.34 micrograms/l. In autopsy material, age-dependent HCB concentrations were found in adipose tissue, increasing with age (total range 0.14-45.4 micrograms/g extractable lipids, n = 80). No age dependence was evident in other organs. In starving people there seems to be only a slight elimination, if any, of the stored organochlorinated compounds. Persistent pesticides remain in a smaller portion of lipids and simulate higher values. Investigations of long-term storage of liver, fatty tissue and whole blood in the Environmental Specimen Bank (-85 degrees C and -170 degrees C) showed sufficient stability of HCB and other xenobiotics.

Adipose Tissue↗

Antihormonal effects of plant extracts. Pharmacodynamic effects of lithospermum officinale on the thyroid gland of rats; comparison with the effects of iodide.

The antithyrotropic activity of freeze-dried-extracts from Lithospermum officinale (Lith. off. FDE) was investigated in the rat. When administered together with TSH, Lith. off. FDE blocked the TSH-induced increase in endocytotic activity of the thyroid glands followed by a strong decline of thyroid hormone levels. Furthermore, when Lith. off. FDE was injected alone it caused a decline in endogenous TSH-levels as well as in thyroidal secretion and thyroid hormone levels. The efficacy of the extract in blocking thyroid secretion was compared to that of potassium iodide and it was found that the effect of Lith. off. FDE was of more rapid onset and of longer duration, suggesting that the FDE may have a different mode of action from that of KJ. A specific interaction between TSH and the active constituents of the plant extract is discussed. Experiments on thyroidectomized and T4 substituted rats have demonstrated as an additional pharmacodynamic effect of Lith. off. FDE an inhibition of peripheral T4-deiodination.

Animals↗

Formation of compounds with antigonadotropic activity from inactive phenolic precursors.

The antigonadotropic activity of Lithospermum and Lycopus species can be attributed to their phenolic components. These compounds represent precursors of biologically active products which are formed by an oxidation step. Complexity and instability of these products aggravates the elucidation of detailed structural properties. Therefore, the type of reaction involved had to be clarified. Among the oxidation products of phenolic substances, the corresponding quinones are found. It can be demonstrated that the reaction between quinones and unoxidized diphenols yields products with strong antigonadotropic activity. This type of reaction - the formation of quinhydrones - is proposed to be engaged in the formation of various products with antigonadotropic activity.

Animals↗

Toxicity of organotin compounds in chicken and rats.

Di-methyltin-dichloride (DMTC), di-butyltin-dichloride (DBTC), di-octyltin-dichloride (DOTC) and two commercial products (CP 1, CP 2) used as stabilizers in plastics induce a dose-related decrease of the thymus weight in young rats when given by gastric intubation for 10 or 14 days; in the chicken a decrease of the bursa Fabricii weight can also be observed. It is of interest, that there are distinct differences in response between the animal species. The sensitivity in acute toxicity tests does not correspond with the sensitivity of thymus and bursa Fabricii. The response is also dependent on the vehicle in which the agent is given.

Animals↗