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Michal Karasek

Publications and source records attributed to Michal Karasek.

29 records · Page 2Linked to original sources

Future of melatonin as a therapeutic agent.

Report of the round table conference summarizing the International Symposium on "Melatonin: Clinical Significance and Therapeutic Applications" is presented in this article. Some sleep disorders and circadian rhythm disturbances are the widely accepted indications for melatonin treatment. However, other possibilities for use of melatonin in the therapy should be also taken into account, including a co-treatment in cancer patients and free radical-related diseases. All aspects of the possible therapeutic use of melatonin as well as its safety, dosage, side effects and contraindications are discussed herein based on the round table conference and they are presented in this paper.

Animals↗

Melatonin concentrations in patients with large goiter before and after surgery.

OBJECTIVES: Surgical removal of a very large goiter may traumatize adjacent anatomical structures. The manipulations that involve superior cervical ganglia may alter melatonin secretion. To test this hypothesis we decided to study diurnal serum melatonin profiles in patients with a very large goiter before and after the surgery. MATERIAL AND METHODS:The study was performed on 10 women (mean age-46.5+/-1.6 years; mean+/-SEM; range 39-54 years) with very large non-toxic nodular goiter (mean thyroid volume-125.8+/-25.9 cm (3); mean+/-SEM; range 82.6-326.7 cm(3)). Diurnal serum melatonin profiles were estimated two days before the operation and 10 days after the surgery. Blood samples were collected at 08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00, 06:00 and 08:00 h. Melatonin concentration was measured using RIA kit. RESULTS: Nocturnal serum melatonin concentrations (at 24, 02, and 04 hours) were significantly higher after the surgery than before the operation. CONCLUSIONS: Very large goiter may compress the superior cervical ganglia altering indirectly the melatonin synthesis. It cannot be excluded, however, that the presence of the large goiter in some other way affects melatonin secretion.

Journal Article↗

Testosterone levels and bone mineral density in young healthy men and in young infertile patients.

OBJECTIVES. Although relatively little information exists concerning bone mineral density (BMD) in men, it has been demonstrated that similarly to observations in women, BMD decreases also with age in men, although to a smaller extent, and osteoporosis is increasingly recognized. Most reports concentrate, however, on men of advanced age. Therefore, we decided to investigate BMD in young healthy volunteers and in young patients suffering from infertility, and to compare it with serum tes-tosterone levels. MATERIAL AND METHODS. The study was performed on 80 men divided into two groups. The first group consisted of 39 young healthy men (mean age 22.1+/-0.3 years; range 20-29). The second group consisted of 41 infertile men with oligozoospermia (mean age 28.0+/-0.5 years; range 23-34). Serum testosterone levels and BMD were measured in each subject. RESULTS. Decrease in BMD (T-score below -0.3) was observed in 35.9% of the subjects in the group of young healthy men and in 60.9% of the subjects in the group of infertile patients. Among these numbers -penia (T-score between -1 and -2.5) was found in 4 subjects (10.3%) in the group of young healthy men and in 13 subjects (31.7%) in the group of infertile patients. There was a positive correlation between testosterone concentrations and BMD as well as T-score both in healthy subjects and in infertile patients. CONCLUSION. Results of the present study indicate that attention should be paid to testosterone deficiency in the young age in terms of the potential risk of decreased bone mineral density in the advanced age.

Journal Article↗

Serum melatonin circadian profile in women suffering from the genital tract cancers.

OBJECTIVES: Although there is increasing evidence that the pineal gland may play a role in human malignancy, the studies on melatonin concentrations in different types of malignant tumors brought about controversial results. However, changes in melatonin concentrations have been observed in some types of human malignant tumors. Therefore we decided to study the circadian melatonin rhythm in patients suffering from malignant tumors of the female genital tract, and to compare them with subjects free from neoplastic disease (healthy volunteers and patients with myomatous uterus). MATERIAL AND METHODS: A total of 46 women were analyzed in this study. The subjects were divided into 3 groups. The first group consisted of 23 patients with malignant tumors of the genital tract (mean age 50.3+/-2.2 years; mean+/-SEM, range 32-77 years). The second group consisted of 16 healthy volunteers (mean age 50.9+/-1.8 years; mean+/-SEM, range 42-63) who served as the first control group, whereas the third group consisted of 7 subjects who suffered from myomatous uterus (mean age 45.7+/-2.3 years; mean+/-SEM, range 39-56) and served as the second control group without malignancy. Blood samples were collected at 08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00, 06:00 and 08:00 h. Melatonin concentration was measured using RIA kit. RESULTS: There were no significant differences in circadian melatonin profiles among the three groups studied. Taking into consideration the type of tumor of the genital tract, significantly lower melatonin secretion has been found in patients with endometrial cancer in comparison with tumor-free control groups, whereas no significant differences in melatonin secretion have been observed between tumor-free control groups and patients with invasive ovarian cancer and squamous cervical cancer. However, significant differences have been observed between endometrial cancer and invasive ovarian cancer. CONCLUSION: Its seems probable that melatonin concentrations in human malignancy may, at least partly, depend on hormone dependency of the particular type of tumor.

Journal Article↗

Comparative quantitative ultrastructural study of pinealocytes in eight mammalian species.

OBJECTIVES: The studies related to quantitative ultrastructural features of mammalian pinealocytes, especially in comparative aspects, are relatively rare. Quantitative ultrastructural studies in many mammalian species are lacking. Because of the existence of differences in diurnal melatonin profiles in various species it seemed interesting to compare the ultrastructure of pinealocytes in various mammalian species, both laboratory and domestic animals. MATERIAL AND METHODS: The pineal glands of the following mammalian species have been examined: mouse, rat, Syrian hamster, gerbil, sheep, horse, pig and European bison. For each species 4 adult animals (2 males and 2 females) were used. Cross-sectional areas of the pinealocyte and its nucleus and the relative volumes of the following cytoplasmic organelles were analyzed: mitochondria, lysosomes, Golgi apparatus, granular endoplasmic reticulum, and lipid droplets. The relative volumes of membrane-bound bodies (MBB) in the pig pinealocytes, pigment granules in the horse pinealocytes, and calcareous concretions in the gerbil pineal gland were also analyzed. In addition, numerical density of dense-core vesicles and "synaptic" ribbons was estimated. RESULTS: Ultrastructure of pinealocytes in examined species shows many common features, and existing differences are of quantitative nature only. The observed qualitative differences include MBB in the pig, abundance of pigment granules in the horse, and calcareous concretions in the gerbil. Relative volumes or the numbers of some cell structures (mitochondria, Golgi apparatus, lipid droplets, dense-core vesicles and "synaptic" ribbons) show distinct interspecie differences, whereas those of other cell structures (granular endoplasmic reticulum, lysosomes) are similar in all studied species. CONCLUSIONS: The ultrastructural features of pinealocytes in all examined species confirm earlier suggestions of high activity of these cells. No distinct correlation has been found between the type of melatonin secretion and ultrastructural patterns of pinealocytes. It should be stressed, however, that the ultrastructure of pinealocytes in the present study was studied during the daytime, whereas differences in melatonin secretion are observed at night.

Journal Article↗

Pineal gland, melatonin and cancer. NEL Review.

Studies on the relationship between the pineal gland, melatonin and neoplastic disease have recently become one of the most fascinating aspects of pineal research. The first data suggesting a link between the pineal and cancer were published 70 years ago. However, the real progress in this area of research has been made in the last two decades. The bulk of the experimental evidence indicates the influence of the pineal gland on the malignant tumor formation and/or growth. The majority of reports point toward the oncostatic action of the pineal, exerted most probably by its hormone, melatonin, via different mechanisms, including modulation of endocrine and immune systems and direct antiproliferative action. The mechanisms of the oncostatic action of the pineal seem to be, however, very complex. There is some indication that the pineal gland may also play a role in human malignancy. Alterations in melatonin concentrations have been demonstrated in various tumor types including breast cancer, prostate cancer, colorectal carcinoma, and uterine cancer. Moreover, melatonin has been reported to be helpful in therapy of advanced cancer of various types. However, detailed 24h melatonin profiles must be studied in large numbers of patients with different types of tumors before determining whether melatonin concentrations have any diagnostic and/or prognostic values in cancer patients. Moreover, well designed clinical trials should be performed on the possible therapeutic significance of melatonin in neoplastic disease.

Journal Article↗

Guest Editorial.

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Journal Article↗

Melatonin in humans-where we are 40 years after its discovery.

Although the pineal gland was well known for more than 2000 years and has been documented since Galen (130-200 AD), for many centuries different theories concerning its function were presented. The organ was believed to be a sphincter (ancient Greeks), the point at which the soul preeminently controls the body (Descartes, 1596-1650), a rudimentary organ (up to the 19th century), and a gland having endocrine function. Endocrine function of the pineal was postulated already at the end of 19th century and the beginning of the 20th century with the notion of antigonadotropic pineal influence, and the functional cooperation between the pineal and hypothalamo-hypophysial axis, but no secretory substance responsible for the gland function was known. In 1958 Lerner and coworkers succeeded in isolating from bovine pineal glands the compound termed melatonin because of its blanching effect on melanophores. This discovery constituted the milestone for further pineal research. Since then the knowledge of the structure and function of the pineal gland has tremendously increased, especially during the last two decades. However, it should be stressed that many problems in pineal research still must be solved. In this paper, the recent knowledge on the role of melatonin in humans is briefly presented.

Journal Article↗

Effect of superior cervical ganglionectomy on the ultrastructure of pinealocytes in the Djungarian hamster (Phodopus sungorus): quantitative study.

OBJECTIVES: Superior cervical ganglia are of crucial importance in regulating the secretion of the pineal hormone melatonin. Changes in pineal morphology have been observed in many mammalian species after sympathectomy. Therefore, we decided to investigate the ultrastructure of Djungarian hamster pinealocytes following superior cervical ganglionectomy. MATERIAL AND METHODS: Eight adult female Djungarian hamsters (Phodopus sungorus) were used in this study. The superior cervical ganglia were removed bilaterally in four animals, whereas the other four animals served as sham-operated controls. The pineal glands were removed four weeks after the operation and processed for electron microscopic study. The cross-sectional areas of pinealocyte and its nucleus, and relative volume of mitochondria, Golgi apparatus, lysosomes, granular endoplasmic reticulum, and glycogen particles as well as the numbers of dense-core vesicles and "synaptic" ribbons were estimated using a digital analyzer connected on-line to IBM-PC computer. Statistical analysis of the data was performed using Student's t test and Snedecor F test. RESULTS: Significant reduction in the cross-sectional areas of the pinealocyte and its nucleus as well as in the relative volumes of mitochondria and glycogen particles was observed after superior cervical ganglionectomy in comparison with sham-operated controls. Sympathectomy resulted also in reduction of the number of dense-core vesicles. On the contrary 2,5 fold increase in the number of "synaptic" ribbons was observed in ganglionectomized animals in comparison to sham-operated controls. CONCLUSION: Deprivation of sympathetic innervation leads in Djungarian hamsters not only to suppression of melatonin synthesis and secretions but, as appears from our studies, induces also morphological changes suggesting lower metabolic and secretory activity of pinealocytes.

Animals↗

Etiopathogenesis of Graves' disease.

Graves' disease is an autoimmune disorder, caused by thyroid-stimulating antibodies, which bind to and activate the thyrotropin receptor on thyroid cells, inducing the synthesis and release of thyroid hormones. It is a polygenic and multifactorial disease that develops as a result of complex interaction between genetic susceptibility and environmental and/or endogenous factors. Graves' disease differs from other autoimmune diseases of the thyroid by specific clinical features, including hyperthyroidism, vascular goitre, ophthalmopathy and--less commonly--infiltrative dermopathy. This article discusses current theories, regarding the etiology and pathogenesis of Graves' disease, including possible predisposing factors, autoimmune aspects of Graves' disease, ophthalmopathy, and dermopathy.

Autoimmunity↗

Ultrastructure of pinealocytes in mice implanted with Colon 38 adenocarcinoma.

OBJECTIVES: Relationship between the pineal gland and neoplastic disease has been repeatedly shown in many both experimental and clinical studies. However, morphological studies of the pineal gland in animals with experimentally-induced tumors are rare. Therefore, we decided to investigate the ultrastructure of pinealocytes in mice with implanted Colon 38 adenocarcinoma. MATERIAL AND METHODS: Male adult B6D2F1 mice were used in this study. The animals were divided into two groups. Eight mice were subcutaneously implanted with Colon 38 cell suspension, whereas the other eight intact animals served as controls. Three weeks after tumor implantation four animals from each group were sacrificed by spinal cord dislocation at 12:00 h or 24:00 h. The pineal glands were removed and processed for electron microscopic studies. The cross-sectional areas of the pinealocyte and its nucleus, and relative volume of mitochondria, Golgi apparatus, lysosomes, granular endoplasmic reticulum, and lipid droplets, as well as the number of dense-core vesicles were estimated using a digital analyzer connected on-line to IBM-PC computer. Statistical analysis of the data was performed using Student's t-test and Snedecor F test. RESULTS: In the pineal glands of the tumor-bearing animals killed during the daytime diminished size of pinealocytes and their nuclei, decreased relative volume of granular endoplasmic reticulum, lysosomes, and lipid droplets as well as decreased number of dense-core vesicles were observed. On the contrary, the relative volumes of mitochondria and Golgi apparatus were increased in these animals. In the tumor-bearing animals killed at night, however, increased cross-sectional areas of pinealocytes, and decreased number of dense-core vesicles were observed. CONCLUSIONS: The results of our study suggest that the presence of the malignant tumor influences the morphology of pineal cells in mice. Considering the fact that different patterns of ultrastructural changes were demonstrated in pinealocytes in different tumor types in various species, it seems that the character of the ultrastructural changes observed in tumor-bearing animals depends on the animal species and tumor type.

Adenocarcinoma↗