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Biomedical subjects

A Lerchl

Publications and source records attributed to A Lerchl.

At least 19 recordsLinked to original sources
PubMed2002

Potentiation of antiproliferative effects of tamoxifen and ethanol on mouse hepatoma cells by melatonin: possible involvement of mitogen-activated protein kinase and induction of apoptosis.

Melatonin, the major secretory product of the pineal gland, is in focus of many research areas because of its ability to scavenge free oxygen radicals and thereby protect cells and tissues from radical damage. Some studies suggest melatonin may be a possible therapeutic agent with potential clinical applications against pathological states due to reactive oxygen species. Here, we investigated the effects of melatonin on the mouse hepatoma cell line HEPA 1-6, coincubated with ethanol, and tamoxifen, respectively. Cell proliferation rates were detected by the 3-[4,5 dimethylthiazol-2-y1]-2,5-diphenyltetrazolium bromide (MTT) proliferation assay. A dose-dependent inhibition of the proliferative activity by melatonin was observed from 640 microM to 3 mM, which was significantly higher (P < 0.01) than with the solvent (ethanol) alone. Concentrations of 320 microM and less had no effect on cell proliferation. This antiproliferative effect might be because of the prolonged activation of mitogen-activated protein kinase which was activated by phosphorylation 15 min after the induction with melatonin. Furthermore, apoptosis was found to be enhanced by melatonin (75% more than with the solvent alone, P < 0.001). Finally, we show that the inhibitory effect of tamoxifen (25 microM) is markedly enhanced by the coincubation with melatonin (1.3 mM) up to 75% (P < 0.001). These data show that the antiproliferative effects of tamoxifen and ethanol, respectively, on mouse hepatoma cell line HEPA 1-6 are enhanced by melatonin. Although at the conditions described here the antiproliferative effects of melatonin occur at supraphysiological concentrations, these data may help to support clinical studies where melatonin is given simultaneously with tamoxifen or other standard chemotherapeutica.

Animals↗
PubMed2001

Clearance of melatonin and 6-sulfatoxymelatonin by hemodialysis in patients with end-stage renal disease.

Patients with end-stage renal disease (ESRD) suffer from a number of related disorders. These include endocrine abnormalities, sleep disturbances, and depression. Melatonin is involved in the synchronization of exogenous zeitgebers with the endogenous rhythms, and it has effects on various psychological factors. As the concentrations of melatonin and the effects of dialysis have only occasionally been investigated in ESRD, we performed a study involving 35 patients, measuring the serum concentrations of melatonin, and of its major metabolite 6-sulfatoxymelatonin (aMT6s), before and after hemodialysis. Serum samples taken during morning hours from a control group (n=11) with intact kidneys served as controls. Patients were dialyzed for approximately 4 hr between 07:00 and 13:00 hr (S1), between 13:00 and 20:00 hr (S2), or between 18:30 and 22:30 hr (S3). Mean melatonin concentrations before hemodialysis were highly elevated when compared with the controls (40.6 vs. 6.7 pg/mL; P<0.001). Although melatonin levels were decreased to 20.3 pg/mL after dialysis, they were still well above the control levels. Likewise, aMT6s concentrations before dialysis were highly elevated in ESRD patients before dialysis when compared with controls (39.5 vs. 2.0 pg/mL; P<0.001), and also decreased by dialysis to levels still well above control levels (25.3 pg/mL). Clearance efficacy was better for melatonin (48.9%) than for aMT6s (36.6%; P<0.05). In ESRD patients, a diurnal rhythm for melatonin was observed (S1, 45.1 pg/mL; S2, 31.5 pg/mL; S3, 48.7 pg/mL; P<0.05), indicating that the normal synthesis rhythm is maintained. None of the following secondary disorders were correlated with melatonin concentrations: insomnia, delayed sleep onset, night-time arousals, and restless-leg syndrome. The reason for this observation is probably the melatonin concentrations, which were so high that no sub-classification could be identified. It is concluded that in ESRD patients, hemodialysis is unable to decrease elevated levels of melatonin and aMT6s to normal values. It is speculated that some of the secondary disorders in ESRD are caused by supraphysiological concentrations of melatonin.

Adult↗
PubMed2001

Is inhibin B a pharmacodynamic parameter for FSH in normal men?

OBJECTIVE: This study aims to investigate the pharmacodynamic effect of FSH on inhibin B serum levels in normal men in order to elucidate the physiological regulation of inhibin B secretion in more detail. DESIGN AND METHODS: Injections of 3000 IU recombinant, human FSH (rhFSH) were followed by single-blinded injections of placebo, 1000 and 2000 IU rhFSH spaced by at least 28 days between injections. RESULTS: After injection of 3000 IU rhFSH, inhibin B values were significantly elevated above baseline for 24, 96 and 120 h (maximal increase after 96 h, mean +/- s.e.m. 303+/-18 pg/ml). Injection of 2000 IU rhFSH led to a significant increase in inhibin B (maximum mean +/- s.e.m. 318+/-20 pg/ml) from 24 to 120 h. Injection of 1000 IU rhFSH led to a significant increase in inhibin B after 96 h (maximum mean +/- s.e.m. 300+/-16 pg/ml). The inhibin B areas under the curve after injection of 2000 and 3000 IU rhFSH were significantly higher than those following the placebo and 1000 IU rhFSH. In the 12 fertile men investigated, at baseline a strong diurnal rhythm of inhibin B parallel to that of testosterone was observed. CONCLUSIONS: Serum inhibin B can be considered only a partial pharmacodynamic parameter of FSH in vivo, since the integrity of the spermatogenic process appears to be a second fundamental component in the regulation of its secretion from the testis.

Adult↗
PubMed2000

Direct suppressive effects of weak magnetic fields (50 Hz and 16 2/3 Hz) on melatonin synthesis in the pineal gland of Djungarian hamsters (Phodopus sungorus).

In many investigations performed thus far on rodents, a suppression of melatonin synthesis was observed when animals were exposed to weak magnetic fields. However, among the several issues not yet resolved is the question of whether the observed changes are caused by direct effects on the pineal gland or by indirect effects, e.g., at the level of the eyes. We, therefore, performed a series of experiments in which direct effects of weak magnetic fields were studied in isolated pineal glands of Djungarian hamsters (Phodopus sungorus). After sacrifice of animals during morning hours, pineal glands were removed and placed individually into glass chambers that were perfused with oxygenated buffer. Experiments (n = 8) lasted for 8 hr. Magnetic fields (1,623 or 50 Hz at 86 microTesla) were generated by Helmholtz coils, and were present during the entire period. In each experiment, 12 exposed, and 12 sham-exposed, pineal glands were placed individually in glass chambers, which were surrounded by identical coils. Because of the design of the coils (bifilament), and the experimental setup (black box), the experimentator was not aware which coil was activated until the results were obtained. After 3.25 hr of adaptation, melatonin production was stimulated by isoproterenol (10(-7) M) for 30 min. Eluted fractions were collected, and melatonin concentrations were measured by radioimmunoassay. Maximum melatonin production was achieved after 5-7 hr. In all experiments, maximum melatonin concentrations were lower in the exposed groups compared with the sham-exposed controls. Statistical analyses for each frequency showed significant suppressive effects at 16(2/3) Hz (P < 0.01), and 50 Hz (P < 0.00). It is concluded that the suppressive effects of magnetic fields on the synthesis of melatonin are a result of primary mechanisms at the level of the pineal gland.

Animals↗
PubMed1999

Sex ratios at birth and environmental temperatures.

The relationship between average monthly air temperature and sex ratios at birth (SRB) was analyzed for children born in Germany during the period 1946-1995. Both the absolute temperature and--more markedly--the monthly temperature deviations from the overall mean were significantly positively correlated with the SRB (P < 0.01) when temperatures were time-lagged against the SRB data by -10 or -11 months. It is concluded that the sex of the offspring is partially determined by environmental temperatures prior to conception.

Female↗
PubMed1999

Isolation method of Leydig cells from mature male Djungarian hamsters (Phodopus sungorus) and their steroidogenic activity in vitro.

For studies addressing the functions of Leydig cells, isolated cells are often better suited than intact animals. Here, the isolation procedure of Leydig cells from adult male Djungarian hamsters (Phodopus sungorus) is described. Cells were isolated using a procedure involving enzymatic dissociation and Percoll-gradient centrifugation. For each experiment, approximately 4.4 x 10(6) Leydig cells from six animals were obtained. The cells showed high steroidogenic responsiveness to physiological (ovine luteinizing hormone (oLH) and human chorionic gonadotropin (hCG)) and nonphysiological (forskolin) stimuli in vitro. Approximately 98% of cells were viable as assessed by trypan blue exclusion, and the purity varied from 80 to 95% as tested by 3 beta-hydroxysteroid dehydrogenase activity. Leydig cells were also identified by a bright yellow halo under phase-contrast microscopy. They contained numerous lipid droplets and showed round nuclei and prominent nucleoli. The cells responded to oLH, hCG and forskolin with an increased testosterone production in a dose-dependent manner. Dose-response curves in these studies suggest that Leydig cells of Djungarian hamsters undergo desensitization, probably due to down regulation of their LH/CG receptors.

Animals↗
PubMed1998

Expression of the gene for the retinal protein peripherin in the pineal gland of humans and Djungarian hamsters (Phodopus sungorus).

This study investigated whether the gene for peripherin, a protein previously considered to play only a role in the retina, may also be expressed in the pineal gland of both Djungarian hamsters (Phodopus sungorus) and humans. After extraction of mRNA from pooled pineal glands of hamsters and from one human pineal gland, mRNA was transcribed into cDNA followed by PCR amplification with specific primers. Clear signals were obtained at the expected sizes of the PCR products. An additional experiment in hamsters revealed that the peripherin gene is expressed throughout the entire 24-h period. Since peripherin is an important protein in the retina stabilizing the photoreceptor discs it is speculated that this protein might also play a structural role in the pineal gland.

Animals↗
PubMed1998

The effects of pulsing magnetic fields on pineal melatonin synthesis in a teleost fish (brook trout, Salvelinus fontinalis).

Based on findings in various mammalian species, where exposure to electromagnetic fields decreased the nocturnal synthesis of the pineal secretory product melatonin, we investigated the effects of magnetic field (MF) exposure in a teleost fish, the brook trout (Salvelinus fontinalis). Fields were generated by Helmholtz coils (maximum flux density 40 microT, frequency 1 Hz, 200 ms on, 800 ms off). Melatonin concentrations were estimated by a specific radioimmunoassay. MF exposure significantly increased night-time pineal (P < 0.001) and serum (P < 0.01) melatonin levels, as compared with the controls. It is suggested that either the pineal glands are directly affected, i.e. by an increased Ca2+-influx into pineal photoreceptors, or that the responses are indirect since induced currents, caused by the rapid rise and decay of the generated MF, may have disturbed the sensory system for electric fields.

Animals↗
PubMed1998

Acceleration of mammary tumorigenesis by exposure of 7,12-dimethylbenz[a]anthracene-treated female rats in a 50-Hz, 100-microT magnetic field: replication study.

In view of the methodological problems of epidemiological studies on associations between residential and occupational exposures to 50/60-Hz magnetic fields (MF) and increased incidence of cancers, laboratory studies are necessary to determine if 50/60-Hz MF can affect cancer development or growth. Recently, it was reported that alternating (50-Hz) MF of low flux density (100 microT) increase tumor growth and progression in a model of breast cancer in female rats in which mammary tumors were induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). The objective of the present study was to determine if a replicate experiment carried out in the same laboratory under the same experimental conditions yields a significant increase in tumor development and growth of similar magnitude. For the MF experiment, a group of 99 female Sprague-Dawley rats was exposed to a homogeneous horizontally polarized MF for 24 h/d (minus time for weighing, tumor palpation, cage cleaning, cage rotation), 7 d/wk; another group of 99 rats was sham exposed. DMBA was administered intragastrically at a dose of 5 mg/rat at the first day of exposure and at weekly intervals thereafter up to a total dose of 20 mg/rat. Duration of MF or sham exposure was 91 d. In both MF-exposed and sham-exposed rats, the first tumors could be recorded 6 wk after the initial DMBA application. At 9 wk after DMBA application, the group of MF-exposed rats exhibited significantly more animals with tumors than the sham-exposed group. This significant difference in the rate of tumor development was observed throughout the subsequent period of exposure. After autopsy, the incidence of macroscopically visible mammary tumors was 62% in controls, but 83% in MF-exposed rats, with the 35% difference between groups being statistically significant. Data substantiate that long-term exposure of DMBA-treated female Sprague-Dawley rats in an alternating MF of low flux density promotes the development and growth of mammary tumors, thus indicating that MF exposure exerts tumor-promoting and/or copromoting effects. Furthermore, the data show that the effects of MF exposure in the DMBA breast cancer model are reproducible if the same experiment is repeated in the same laboratory.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Changes in the seasonality of mortality in Germany from 1946 to 1995: the role of temperature.

Based on records from the Federal Bureau for Statistics of Germany, the seasonality of mortality was investigated for the period 1946-1995. Lowest mortality rates were found during summer (August or September) while highest values were found in winter (January through March). Non-linear regression of all monthly mortality data with the average monthly temperatures in Germany revealed a significant negative relationship (r = -0.739; n = 600; P < 0.0001). The fact that the differences between the long-range monthly temperatures and the individual monthly temperatures also showed a distinct relationship to the mortality rates speaks against a mere coincidence of both parameters. The amplitude of this seasonal rhythm declined steadily within the observation period. It is concluded that low temperatures cause an increase in mortality rates and that this effect has become less important during recent decades due to the increased use of central heating and because of improvements in the public health system.

Germany↗
PubMed1998

Seasonality of sex ratio in Germany.

It was investigated whether there is a seasonal variation in sex ratio at birth in Germany. The analysis was based on records from the German Bureau for Statistics, covering the period from 1946 to 1995. A highly significant (P < or = 0.001), albeit low-amplitude rhythm was found with two peaks in May and December, and two nadirs in March and October. No correlations were found between sex ratios and seasonal birth rates during this period.

Female↗
PubMed1998

Urinary 6-sulfatoxymelatonin profiles in male Djungarian hamsters (Phodopus sungorus) responding and not responding to short-day photoperiods: possible role of elevated daytime levels.

The lack of endocrine and physiological responses of some Djungarian hamsters (Phodopus sungorus) to the transition from long to short photoperiods (L:D 16:8 --> L:D 8:16) has been known for a long time but is not yet understood. We investigated the role of melatonin synthesis in this context because melatonin, as part of the circadian system, may play a role in non-responsiveness. In ten responding and ten non-responding male hamsters, the urinary 24 hr 6-sulfatoxymelatonin (aMT6s) profiles under L:D 8:16 and L:D 16:8 were measured. Both short day responding and non-responding hamsters showed diurnal aMT6s excretion rhythms. Whereas responders reacted to the transition L:D 16:8 --> L:D 8:16 with a marked elevation of aMT6s excretion, in non-responders no adjustment of the melatonin rhythm to the change of the photoperiod was seen. Furthermore, under L:D 16:8 the daytime levels of aMT6s were significantly (P<0.001) lower in responders compared to non-responders whereas under L:D 8:16 these levels were higher (P<0.01). It is speculated that high daytime levels of aMT6s under long-day photoperiods in non-responders result in down-regulation of melatonin receptors of the nucleus suprachiasmaticus, the pacemaker for the pineal gland, leading to a lack of response to the transition to short-day photoperiods.

Animals↗
PubMed1998

Exposure of female rats to a 100-microT 50 Hz magnetic field does not induce consistent changes in nocturnal levels of melatonin.

The hypothesis whereby alternating (50 or 60 Hz) magnetic fields such as those produced by electric power reduce the nocturnal production of melatonin in the pineal gland and thereby indirectly enhance development and growth of breast cancer has attracted a great deal of interest. In view of the potential importance of this hypothesis that there is a link between electric power and breast cancer, which is also known as the "melatonin hypothesis", we undertook various experiments in female Sprague-Dawley rats to evaluate whether 100-microT 50 Hz magnetic-field exposure, i.e. a flux density shown recently to exert a tumor (co)promoting effect in the 7,12-dimethylbenz[a]anthracene (DMBA) model of breast cancer in Sprague-Dawley rats, consistently reduces melatonin levels and, if not, which factors may be involved in the inconsistent effects of magnetic-field exposure on production of melatonin. Long-term exposure of female Sprague-Dawley rats to magnetic fields for 13 weeks did not alter the nocturnal levels of melatonin in the pineal gland or serum (determined 5 h after the onset of darkness) significantly, irrespective of whether rats were treated with DMBA or not. In one experiment, when blood was sampled 3, 5 and 6 h after the onset of darkness after 2 weeks of magnetic-field or sham exposure, a significant decrease in melatonin was seen in magnetic-field-exposed rats at 6 h. However, the results could not be reproduced in two subsequent experiments in other groups of rats. Shorter (1 day, 1 week) or longer (4, 8, 13 weeks) exposure periods also did not result in any significant effects of the magnetic field on melatonin levels when blood sampling was performed either 5 or 6 h after onset of the dark phase. Various potential sources of variation in melatonin levels or in magnetic-field effects on melatonin levels were evaluated, but the reason(s) for the inconsistent effect of magnetic-field exposure remains unclear. Thus the present study failed to demonstrate a consistent effect of 100-microT 50 Hz magnetic-field exposure on melatonin levels in Sprague-Dawley rats.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Growth retardation, testicular stimulation, and increased melatonin synthesis by weak magnetic fields (50 Hz) in Djungarian hamsters, Phodopus sungorus.

Male Djungarian hamsters (Phodopus sungorus; 45 animals per group) were either sham-exposed or exposed to a sinusoidal magnetic field for 56 days (Experiment 1: 50 Hz, 450 microTesla peak; max. dB/dt = 140 mTesla s(-1); 24 hrs day(-1)). Except for day 7, no effects were observed with respect to body weights during exposure. However, testicular cell numbers were significantly increased by exposure (tetraploid (4C): p=0.022; diploid (2C): p=0.039). Rectangular magnetic fields (Experiment 2: 360 microTesla; max. dB/dt = 2.5 Tesla s(-1)) caused a significant (p<0.001) but transient suppressing effect on body weights. Significant increases were also observed in testicular cell numbers (4C: p=0.034; haploid (1C): p=0.014) and in serum melatonin (p=0.001). It is concluded that weak magnetic fields may affect reproductive and physiological functions in the mammalian species tested and that the degree of these effects depends upon the fields' gradients.

Animals↗
PubMed1997

Episodic variations of prolactin, thyroid-stimulating hormone, luteinizing hormone, melatonin and cortisol in infertile women with subclinical hypothyroidism.

Preliminary data have suggested that female infertility due to corpus luteum insufficiency may be caused by subclinical hypothyroidism [exaggerated thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH) stimulation]. L-Thyroxine supplementation has been recommended to achieve pregnancies in subclinical hypothyroid women. This controlled study was carried out in order to investigate the biochemical diagnosis of subclinical hypothyroidism as a possible infertility factor. Five infertile patients (aged 25-36 years) with subclinical hypothyroidism (n = 4, stimulated TSH >20 microU/ml) or primary hypothyroidism (n = 1) and five healthy controls (aged 22-39 years) with normal thyroid function (stimulated TSH <15 microU/ml), regular cycles and no history of infertility were studied in the early follicular phase. In the pre-study evaluation, eight of 23 volunteers (34.8%) had to be excluded because of subclinical hypothyroidism with stimulated TSH values (TSHs) >15 microU/ml. Cycle function of patients and controls was compared by the method of LH pulse pattern analysis. Therefore blood samples were drawn every 10 min during a 24 h period. Sleep was recorded from midnight to 7 a.m. Repetition of the TRH tests at the end of the 24 h blood sampling period confirmed the difference in stimulated TSH values of the two study groups. Pulse analysis for luteinizing hormone (LH), TSH and prolactin showed no differences between patients and controls for pulse frequency, amplitude, height, length, area under curve (AUC) and the 24 h mean. Even the hypothyroid patient had a normal LH pulse pattern. Additional measurement of melatonin in pooled sera every 30 min gave the well-documented diurnal profiles during day and night for both groups. Patients had significantly higher melatonin values at seven time points during the night. Peaks for LH, TSH, prolactin and cortisol were correlated with the sleep stages wake, rapid eye movement, 1 + 2 and 3 + 4. We concluded that corpus luteum insufficiency in female infertility cannot be explained by subclinical hypothyroidism and thus should not be treated with L-thyroxine for fertility reasons.

Adult↗