C. Bartsch - Academia.edu (original) (raw)
Papers by C. Bartsch
Die Pharmazie, 1998
Using melatonin (MT) as a circadian synchroniser in humans to treat a variety of rhythm disorders... more Using melatonin (MT) as a circadian synchroniser in humans to treat a variety of rhythm disorders, it is desirable to develop controlled-release dosage forms that deliver MT in accordance with its endogenous secretory pattern as well as preparations that release MT in a pulsatile way. In this paper we describe two oral pulsatile dosage forms containing 10 mg MT each (capsules B and C) and a fast-release form containing 5 mg MT (capsule A) studied in a randomised single-dose, threefold cross-over study in 15 healthy male volunteers. The concentrations of both MT in serum and its main metabolite 6-sulfatoxymelatonin (aMT6s) in urine were analysed by means of specific radioimmunoassays up to 10 h p.a. of the MT preparations. Mean peak concentrations of MT in serum were reached between 0.5 h and 0.75 h (Cmax[1] pmol/ml): 20.7 (A), 16.4 (B), 9.7 (C). The capsules B and C released a second MT pulse after about 3.5 h with Cmax[2] of 13.0 and 17.5 pmol/ml, respectively. Dose proportionality...
Bislang ist nur fur Melatonin eine Wirkung hi nsichtlich der Verminderung eines Jetlags nachgewie... more Bislang ist nur fur Melatonin eine Wirkung hi nsichtlich der Verminderung eines Jetlags nachgewiesen: 1. Nach einer Reise fiber 5 oder mehr Zeitzonen kann die Einnahme von Melatonin 0,5–5 zur Zeit des Schlafengehens am Zielort den Jetlag vermindern. 2. Die Wirkung ist umso besser, je mehr Zeitzonen wahrend des Flugs uberstrichen wurden. 3. Bessere Wirkungen werden bei Fliigen in ostlicher als in westlicher Richtung erzielt, was sich aus der Interaktion zwischen exogenem und dem mit dem Kerntemperaturrhythrnus in tagesperiodischer Phasenbeziehung stehendem endogenem Melatonin erklart. 4. Die Wirkung gilt nach 9 von to kontrollierten Studien als gesichert. Es fehlen jedoch systematische Dosis-Wirkungs-Kurven; unsicher ist des Weiteren die Bioverfugbarkeit der bislang in Deutschland nicht eingefiihrten unterschiedlich galenisch aufbereiteten Praparate. 5.Das Nutzen-Risiko-Profil jeglicher Form der Melatoninanwendung ist unzureichend geldart. Daher wird derzeit von einer Einnahme abgera...
Journal of Neural Transmission, 1988
An in vitro human melanoma cell assay was used to work up the partial purification of (a) low mol... more An in vitro human melanoma cell assay was used to work up the partial purification of (a) low molecular weight (MW) substance(s) from aqueous extracts of ovine pineal tissue shown to contain a growth-inhibiting activity. A combination of paper chromatography, ion-exchange and reverse-phase high performance liquid chromatography with post-column antitumor assay has been developed. This allows a specific identification of an ovine pineal factor (MW less than 500) which inhibits the growth of human melanoma cells in vitro. The substance was partially purified to about 1,000 times as compared to the IC100-value of the starting material (retentate 5). The growth inhibition of human melanoma cells in culture was complete at a dose of 0.1 microgram/ml of purified pineal factor(s). It was demonstrated that the activity of this pineal compound differs from some substances known to be present in the pineal, such as melatonin, serotonin, peridines and beta-carbolines. The activity was not destroyed by treatment with proteolytic enzymes.
Experimental and Toxicologic Pathology, 2000
Nocturnal (23.00-07.00 h) urinary melatonin and total biopterin (tBI; after acidic oxidation of r... more Nocturnal (23.00-07.00 h) urinary melatonin and total biopterin (tBI; after acidic oxidation of reduced biopterins) were analyzed during the growth of two passages of a mammary tumor line in female F344 Fischer rats. In addition, nocturnal (02.00-03.00 h) peak concentrations of pineal melatonin in plasma were analyzed when tumors had reached comparable average tumor volumes of 25-30 cm3. Since tetrahydrobiopterin (BH4) is produced by murine macrophages in response to interferon-gamma released by activated T lymphocytes, measurements of tBI can serve to estimate the state of cellular immunity. At passage 2, a slow-growing localized carcinosarcoma, tBI showed a progressing increase during tumor growth reaching more than 200% (p < 0.05-0.005) of controls by the end of the experiment. Urinary and plasma melatonin were elevated by 30-50% (p < 0.05) and 42% respectively. At passage 12, a fast-growing metastasizing sarcoma, a depression of about 20-30% was found for tBI (p < 0.05) and urinary melatonin (p < 0.025); plasma melatonin was depleted by 70% (p < 0.005). Parallel changes of both parameters at each tumor passage indicate a close link between the pineal hormone melatonin and cellular immunity. The opposite trends observed at the two passages indicate a clear stimulation of the immune system and the pineal gland at early but inhibition at advanced stages of cancer.
Experientia, 1995
The protective function of the pineal hormone melatonin in the etiology of cancer and carcinogeni... more The protective function of the pineal hormone melatonin in the etiology of cancer and carcinogenic activation is increasingly well-established. Low melatonin levels seem to parallel cancer growth. The question arises as to which factors cause the depression of melatonin levels and what the direct effects are. Melatonin is known to be metabolized in the liver by hydroxylation and subsequent conjugation yielding 6-sulfatoxymelatonin as a main product. Nevertheless, the microsomal monoxygenases catalyzing the first step have been poorly investigated. To further characterize these enzymes, typical inducers of three different sub-classes, namely phenobarbital, 7,12-dimethylbenz[a]anthracene, and 17 beta-estradiol, were administered to female Fischer rats. Circadian urinary excretion patterns of melatonin and 6-sulfatoxymelatonin were determined over a 24-hour period on the third (second) day of induction. Liver homogenates were used to monitor the in vitro conversion of melatonin or 6-hydroxymelatonin to 6-sulfatoxymelatonin. Results of both approaches showed the microsomal monoxygenases catalyzing the 6-hydroxylation of melatonin to be strongly inducible by phenobarbital and to a lesser degree by the polyaromatic hydrocarbon 7,12-dimethylbenz[a]anthracene. The dramatic depletion of circulating melatonin as a result of these induction patterns and its possible implications for oncogenesis are discussed.
International Journal of Developmental Biology, 1998
Support or inhibition of DAG-induced head formation: Hydra magnipapillata can be caused to form e... more Support or inhibition of DAG-induced head formation: Hydra magnipapillata can be caused to form ectopic head structures by periodictreatmentwith PKC activators such as diacylglycerol (DAG). This ectopic head formation is supported by an extract from the ovine pineal gland that contains low-molecular-weight compounds. The frequency of ectopic head formation is also increased when DAG is paired with one of several lipophilic hormonal factors: (1) pinoline, a putative pineal hormone derived from tryptophan, (2) 12-S-HETE, a paracrine derivative of arachidonic acid, or (3) 1alpha, 25 dihydroxyvitamine D3, a hormonal factor also known as calcitriol. Dose-response curves were non-monotonic passing a maximum at low dosages. By contrast, DAG lost its capacity to induce ectopic head structures when it was paired with the provitamin D3, cholecalciferol. Patterning the head: one eicosanoid was found which influences patterning without being combined with DAG: 12-R-HETE caused growth-based elon...
Frontiers of Hormone Research, 1997
Journal of Pineal Research, Feb 1, 1990
The aim of this study was to investigate whether the tumor-inhibiting activity present in the rat... more The aim of this study was to investigate whether the tumor-inhibiting activity present in the rat pineal gland undergoes seasonal fluctuations as do other pineal substances. Crude ethanol extracts of rat pineal glands were tested for tumor-inhibiting activity in an in vitro microbioassay using human erythroleukemia cells which could not be inhibited by melatonin. Highest activity was detected in summer and least inhibition and even stimulation were observed in winter. There were no differences in activity between animals of different age, sex, or strain. Therefore, season seems to be the factor that exerts the most important influence on the content of tumor-inhibiting activity in the rat pineal gland. Correlation with seasonality in the occurrence of cancer is discussed.
Neuro Endocrinology Letters, 2004
Detection of the antiestrogenic effect of melatonin on various breast cancer cell lines and its d... more Detection of the antiestrogenic effect of melatonin on various breast cancer cell lines and its dependence of the differential expression of estrogen receptors (ERα and ERβ) and melatonin receptors (mt1 and RZRα). SETTING AND DESIGN: Dose-response curves of estradiol were determined in 6 different breast cancer cell lines using a colorimetric proliferation assay in the absence or presence of various melatonin concentrations. METHODS: In order to detect the minor growth inhibitory effect of melatonin, a simple yet novel approach was employed: instead of incubating cells at single estradiol-concentrations at increasing melatonin levels, breast cancer cells were grown in microwell-plates for 4 days at increasing concentrations of estradiol (10-12 M-10-10 M) in the absence or presence of melatonin (10-9 M-10-8 M). Cell number was determined using Alamar blue and colorimetry. RT-PCR was performed for the expression of ERα, ERβ, RZRα and mt1. RESULTS: Melatonin at concentrations of 10-9 M and 5x10-9 M shifted the dose-response curves of estradiol to higher concentrations. Responsiveness to melatonin depended on expression of ERα but not on ERβ. mRNA of ERβ was not detectable in the breast cancer cell lines used. Only small amounts of mt1 transcripts were detectable in MCF-7 cells of one source. In MCF-7 cells transfected with the mt1 gene and in an ovarian cancer cell line mt1 was expressed at significant levels. RZRα was expressed in all tested cell lines at different amounts. CONCLUSION: The growth of all ERα-positive breast cancer cell lines can be inhibited by melatonin. The effect in most cell lines is weak yet clearly reproducible. RZRα clearly contributes to the growth inhibitory effect of melatonin.
The Pineal Gland and Cancer, 2001
European Journal of Integrative Medicine, 2015
The Pineal Gland and Cancer, 2001
Neuro endocrinology letters
Die Pharmazie, 1998
Using melatonin (MT) as a circadian synchroniser in humans to treat a variety of rhythm disorders... more Using melatonin (MT) as a circadian synchroniser in humans to treat a variety of rhythm disorders, it is desirable to develop controlled-release dosage forms that deliver MT in accordance with its endogenous secretory pattern as well as preparations that release MT in a pulsatile way. In this paper we describe two oral pulsatile dosage forms containing 10 mg MT each (capsules B and C) and a fast-release form containing 5 mg MT (capsule A) studied in a randomised single-dose, threefold cross-over study in 15 healthy male volunteers. The concentrations of both MT in serum and its main metabolite 6-sulfatoxymelatonin (aMT6s) in urine were analysed by means of specific radioimmunoassays up to 10 h p.a. of the MT preparations. Mean peak concentrations of MT in serum were reached between 0.5 h and 0.75 h (Cmax[1] pmol/ml): 20.7 (A), 16.4 (B), 9.7 (C). The capsules B and C released a second MT pulse after about 3.5 h with Cmax[2] of 13.0 and 17.5 pmol/ml, respectively. Dose proportionality...
Bislang ist nur fur Melatonin eine Wirkung hi nsichtlich der Verminderung eines Jetlags nachgewie... more Bislang ist nur fur Melatonin eine Wirkung hi nsichtlich der Verminderung eines Jetlags nachgewiesen: 1. Nach einer Reise fiber 5 oder mehr Zeitzonen kann die Einnahme von Melatonin 0,5–5 zur Zeit des Schlafengehens am Zielort den Jetlag vermindern. 2. Die Wirkung ist umso besser, je mehr Zeitzonen wahrend des Flugs uberstrichen wurden. 3. Bessere Wirkungen werden bei Fliigen in ostlicher als in westlicher Richtung erzielt, was sich aus der Interaktion zwischen exogenem und dem mit dem Kerntemperaturrhythrnus in tagesperiodischer Phasenbeziehung stehendem endogenem Melatonin erklart. 4. Die Wirkung gilt nach 9 von to kontrollierten Studien als gesichert. Es fehlen jedoch systematische Dosis-Wirkungs-Kurven; unsicher ist des Weiteren die Bioverfugbarkeit der bislang in Deutschland nicht eingefiihrten unterschiedlich galenisch aufbereiteten Praparate. 5.Das Nutzen-Risiko-Profil jeglicher Form der Melatoninanwendung ist unzureichend geldart. Daher wird derzeit von einer Einnahme abgera...
Journal of Neural Transmission, 1988
An in vitro human melanoma cell assay was used to work up the partial purification of (a) low mol... more An in vitro human melanoma cell assay was used to work up the partial purification of (a) low molecular weight (MW) substance(s) from aqueous extracts of ovine pineal tissue shown to contain a growth-inhibiting activity. A combination of paper chromatography, ion-exchange and reverse-phase high performance liquid chromatography with post-column antitumor assay has been developed. This allows a specific identification of an ovine pineal factor (MW less than 500) which inhibits the growth of human melanoma cells in vitro. The substance was partially purified to about 1,000 times as compared to the IC100-value of the starting material (retentate 5). The growth inhibition of human melanoma cells in culture was complete at a dose of 0.1 microgram/ml of purified pineal factor(s). It was demonstrated that the activity of this pineal compound differs from some substances known to be present in the pineal, such as melatonin, serotonin, peridines and beta-carbolines. The activity was not destroyed by treatment with proteolytic enzymes.
Experimental and Toxicologic Pathology, 2000
Nocturnal (23.00-07.00 h) urinary melatonin and total biopterin (tBI; after acidic oxidation of r... more Nocturnal (23.00-07.00 h) urinary melatonin and total biopterin (tBI; after acidic oxidation of reduced biopterins) were analyzed during the growth of two passages of a mammary tumor line in female F344 Fischer rats. In addition, nocturnal (02.00-03.00 h) peak concentrations of pineal melatonin in plasma were analyzed when tumors had reached comparable average tumor volumes of 25-30 cm3. Since tetrahydrobiopterin (BH4) is produced by murine macrophages in response to interferon-gamma released by activated T lymphocytes, measurements of tBI can serve to estimate the state of cellular immunity. At passage 2, a slow-growing localized carcinosarcoma, tBI showed a progressing increase during tumor growth reaching more than 200% (p < 0.05-0.005) of controls by the end of the experiment. Urinary and plasma melatonin were elevated by 30-50% (p < 0.05) and 42% respectively. At passage 12, a fast-growing metastasizing sarcoma, a depression of about 20-30% was found for tBI (p < 0.05) and urinary melatonin (p < 0.025); plasma melatonin was depleted by 70% (p < 0.005). Parallel changes of both parameters at each tumor passage indicate a close link between the pineal hormone melatonin and cellular immunity. The opposite trends observed at the two passages indicate a clear stimulation of the immune system and the pineal gland at early but inhibition at advanced stages of cancer.
Experientia, 1995
The protective function of the pineal hormone melatonin in the etiology of cancer and carcinogeni... more The protective function of the pineal hormone melatonin in the etiology of cancer and carcinogenic activation is increasingly well-established. Low melatonin levels seem to parallel cancer growth. The question arises as to which factors cause the depression of melatonin levels and what the direct effects are. Melatonin is known to be metabolized in the liver by hydroxylation and subsequent conjugation yielding 6-sulfatoxymelatonin as a main product. Nevertheless, the microsomal monoxygenases catalyzing the first step have been poorly investigated. To further characterize these enzymes, typical inducers of three different sub-classes, namely phenobarbital, 7,12-dimethylbenz[a]anthracene, and 17 beta-estradiol, were administered to female Fischer rats. Circadian urinary excretion patterns of melatonin and 6-sulfatoxymelatonin were determined over a 24-hour period on the third (second) day of induction. Liver homogenates were used to monitor the in vitro conversion of melatonin or 6-hydroxymelatonin to 6-sulfatoxymelatonin. Results of both approaches showed the microsomal monoxygenases catalyzing the 6-hydroxylation of melatonin to be strongly inducible by phenobarbital and to a lesser degree by the polyaromatic hydrocarbon 7,12-dimethylbenz[a]anthracene. The dramatic depletion of circulating melatonin as a result of these induction patterns and its possible implications for oncogenesis are discussed.
International Journal of Developmental Biology, 1998
Support or inhibition of DAG-induced head formation: Hydra magnipapillata can be caused to form e... more Support or inhibition of DAG-induced head formation: Hydra magnipapillata can be caused to form ectopic head structures by periodictreatmentwith PKC activators such as diacylglycerol (DAG). This ectopic head formation is supported by an extract from the ovine pineal gland that contains low-molecular-weight compounds. The frequency of ectopic head formation is also increased when DAG is paired with one of several lipophilic hormonal factors: (1) pinoline, a putative pineal hormone derived from tryptophan, (2) 12-S-HETE, a paracrine derivative of arachidonic acid, or (3) 1alpha, 25 dihydroxyvitamine D3, a hormonal factor also known as calcitriol. Dose-response curves were non-monotonic passing a maximum at low dosages. By contrast, DAG lost its capacity to induce ectopic head structures when it was paired with the provitamin D3, cholecalciferol. Patterning the head: one eicosanoid was found which influences patterning without being combined with DAG: 12-R-HETE caused growth-based elon...
Frontiers of Hormone Research, 1997
Journal of Pineal Research, Feb 1, 1990
The aim of this study was to investigate whether the tumor-inhibiting activity present in the rat... more The aim of this study was to investigate whether the tumor-inhibiting activity present in the rat pineal gland undergoes seasonal fluctuations as do other pineal substances. Crude ethanol extracts of rat pineal glands were tested for tumor-inhibiting activity in an in vitro microbioassay using human erythroleukemia cells which could not be inhibited by melatonin. Highest activity was detected in summer and least inhibition and even stimulation were observed in winter. There were no differences in activity between animals of different age, sex, or strain. Therefore, season seems to be the factor that exerts the most important influence on the content of tumor-inhibiting activity in the rat pineal gland. Correlation with seasonality in the occurrence of cancer is discussed.
Neuro Endocrinology Letters, 2004
Detection of the antiestrogenic effect of melatonin on various breast cancer cell lines and its d... more Detection of the antiestrogenic effect of melatonin on various breast cancer cell lines and its dependence of the differential expression of estrogen receptors (ERα and ERβ) and melatonin receptors (mt1 and RZRα). SETTING AND DESIGN: Dose-response curves of estradiol were determined in 6 different breast cancer cell lines using a colorimetric proliferation assay in the absence or presence of various melatonin concentrations. METHODS: In order to detect the minor growth inhibitory effect of melatonin, a simple yet novel approach was employed: instead of incubating cells at single estradiol-concentrations at increasing melatonin levels, breast cancer cells were grown in microwell-plates for 4 days at increasing concentrations of estradiol (10-12 M-10-10 M) in the absence or presence of melatonin (10-9 M-10-8 M). Cell number was determined using Alamar blue and colorimetry. RT-PCR was performed for the expression of ERα, ERβ, RZRα and mt1. RESULTS: Melatonin at concentrations of 10-9 M and 5x10-9 M shifted the dose-response curves of estradiol to higher concentrations. Responsiveness to melatonin depended on expression of ERα but not on ERβ. mRNA of ERβ was not detectable in the breast cancer cell lines used. Only small amounts of mt1 transcripts were detectable in MCF-7 cells of one source. In MCF-7 cells transfected with the mt1 gene and in an ovarian cancer cell line mt1 was expressed at significant levels. RZRα was expressed in all tested cell lines at different amounts. CONCLUSION: The growth of all ERα-positive breast cancer cell lines can be inhibited by melatonin. The effect in most cell lines is weak yet clearly reproducible. RZRα clearly contributes to the growth inhibitory effect of melatonin.
The Pineal Gland and Cancer, 2001
European Journal of Integrative Medicine, 2015
The Pineal Gland and Cancer, 2001
Neuro endocrinology letters