Search NEL Online

Journal Article 2003; 24(5): 329-333 PubMed PMID: 14647006 Citation  Keywords:  Aged, Aging:physiology, Cells, Cultured, Euchromatin:drug effects, Heterochromatin:drug effects, Hot Temperature, Humans, Lymphocytes:cytology, Oligopeptides:pharmacology, Protein Denaturation, Ribosomal Proteins:genetics, Transcriptional Activation:drug .   

UNLABELLED: OBJECTIVES and design. We have studied the effect of synthetic peptide Epitalon on the activity of ribosomal genes, denaturation parameters of total heterochromatin, polymorphism of structural C-heterochromatin and the variability of facultative heterochromatin in cultured lymphocytes of persons aged 76-80 years.

RESULTS: The obtained data demonstrate that Epitalon induces the activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin and the release of genes repressed due to the age-related condensation of euchromatic chromosome regions.

CONCLUSIONS: Epitalon has shown its ability to activate chromatin by modifying heterochromatin and heterochromatinized chromosome regions in the cells of older persons....

Read abstract

Journal Article 2003; 24(5): 325-328 PubMed PMID: 14647005 Citation  Keywords:  Aldosterone:urine, Blood Pressure:genetics, Genetic Markers, Humans, Hypertension, Renal:genetics, Insulin:genetics, Middle Aged, Minisatellite Repeats, Phenotype, Pilot Projects, Polymorphism, Restriction Fragment Length, Potassium:urine, Quantitative Tr.   

BACKGROUND: Blood pressure regulation is a complex process influenced by numerous environmental and genetic factors. Consequently, there's no cookie-cutter approach for the elucidation of of the genetic mechanism involved. One of the goals of molecular geneticists in the field of hypertension is to unravel the genetic architecture of blood pressure regulation.

METHODS: With the aim of identifying quantitative trait loci participating in the control of blood pressure, we carried out a pilot study on a sample population of middle-aged, U.S. Caucasians (44 subjects). The design of the study was to search for associations between clinical variables of blood pressure regulation pertaining to the renin-angiotensin-aldosterone system (systolic and diastolic blood pressures, urinary excretion of sodium, potassium and aldosterone, plasma renin activity) and a genetic marker at a candidate gene locus - the human insulin gene (INS) RESULTS: We observed significant associations between a variable number of tandem repeats (VNTR) marker (visualized as a biallelic, class I/class III marker system) localized at the 5' end of the human INS gene, and plasma renin activity and urinary sodium, potassium and aldosterone.

CONCLUSION: Our results indicate that between 6 and 10 QTLs with comparable effects could be involved in blood pressure regulation via the rennin angiotensin system....

Read abstract

Journal Article 2003; 24(5): 293-303 PubMed PMID: 14647000 Citation  Keywords:  Animals, Humans, Oxidative Stress:physiology, Pineal Gland:physiology, Thyroid Diseases:metabolism, Thyroid Gland:metabolism,.   

: Reactive oxygen species (ROS) play an important role in physiological processes, but - when being in excess - ROS cause oxidative damage to molecules. Under physiological conditions, the production and detoxification of ROS are more-or-less balanced. Also in the thyroid, ROS and free radicals participate in physiological and pathological processes in the gland. For example, hydrogen peroxide (H2O2) is crucial for thyroid hormone biosynthesis, acting at different steps of the process. Additionally, H2O2 is believed to participate in the Wolff-Chaikoff's effect, undergoing in conditions of iodide excess in the thyroid. Much evidence has been accumulated indicating that oxidative stress is involved in pathomechanism of thyroid disease, e.g., Graves' disease, goiter formation or thyroid cancer. Melatonin (N-acetyl-5-methoxytryptamine) - the main secretory product of the pineal gland - is a well-known antioxidant and free radical scavenger, widely distributed in the organism. Mutual relationships between the pineal gland and the thyroid have - for a long time - been a subject of intensive research. The abundant to-date's evidence relates mostly to the inhibitory action of melatonin on the thyroid growth and function and - to a lesser extent - to the stimulatory effects of thyroid hormones on the pineal gland. It is highly probable that under physiological conditions melatonin and, possibly, other antioxidants regulate ROS generation for thyroid hormone synthesis. We believe that melatonin may protect against extensive oxidative damage in the course of certain thyroid disorders or in case of a harmful action of some external factors on the thyroid. Thus, oxidative damage and the protective action of antioxidants, melatonin included, may occur during both physiological and pathological processes in the thyroid, however, this assumption, requires further studies....

Read abstract

Journal Article 2003; 24(5): 283-292 PubMed PMID: 14646999 Citation  Keywords:  Cytokines:physiology, Humans, Neuroimmunomodulation:physiology, Neurosecretory Systems:immunology, Stress, Psychological:immunology, Time Factors,.   

OBJECTIVES: Previously, a large number of studies reported that psychological stress and psychiatric illness reduces immune responsiveness. However, it turned out that stress reduces immune responsiveness is an oversimplified statement because the interactions between central nervous system, endocrine system and the immune system are undoubtedly complex. Therefore, this study aims in reviewing mental stress models (e.g. brief and written examination stress as subacute and acute type of stressor) that have been utilized to understand the effect of stress on the neuroendocrine and immune systems.

METHODS: The published findings from human mental stress models on catecholamines, cortisol, prolactin levels and on T helper (Th) 1 and 2-induced cytokines are presented and discussed with respect to the in vitro and in vivo effects of glucocorticoids, catecholamines, and prolactin on the induction of cytokines.

RESULTS: This review shows evidence that short-time (minutes) or preparation to a written examination, in those students who are stressed, induces the production of proinflammatory cytokines which may be related to Th1 response. However, longer mental stress (days) causes dysregulation in the immune function by shifting the cytokine response to Th2 response.

CONCLUSIONS: The outcome from neuroendocrine and immune function prior to, following and after mental stress depends on multiple variables most importantly on the amount of stress, exposure time, coping behavior and adjustment of the individual. A few minutes of stress may improve immune performance but longer times of mental stress have detrimental effects that may lead to loss of immune integrity. Furthermore, studies on stress and common heath problems are necessary to increase our knowledge and understanding of the mechanisms responsible for producing neuroendocrine-induced immune changes in health and common diseases....

Read abstract  Full text PDF

Journal Article 2003; 24(3-4): 269-273 PubMed PMID: 14523369 Citation  Keywords:  Adenocarcinoma:pathology, Animals, Cell Nucleus:ultrastructure, Circadian Rhythm:physiology, Colonic Neoplasms:pathology, Male, Mice, Mice, Inbred Strains, Neoplasm Transplantation, Organelles:ultrastructure, Pineal Gland:cytology,.   

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....

Read abstract

Journal Article 2003; 24(3-4): 263-268 PubMed PMID: 14523368 Citation  Keywords:  Aging, Biogenic Amines:metabolism, CD4-Positive T-Lymphocytes:metabolism, CD8-Positive T-Lymphocytes:metabolism, Cell Division, Child, Preschool, Humans, Image Interpretation, Computer-Assisted, Immunohistochemistry, Infant, Peptide Hormones:biosynthesis,.   

OBJECTIVES: The immunocytochemical study of the localization of hormones in thymic cells has been performed to clarify possible correlations of their expression with proliferative activity of thymocytes.

METHODS: We used commercial antibodies to serotonin, melatonin, somatostatin, glucagon, gastrin, beta-endorphin and histamine, and ABP or BSP kits for visualization of reaction. Computer image analysis was used to find correlations between hormone production and proliferative activity of thymocytes.

RESULTS: Different subpopulations of thymocytes are able to produce hormones: precursors of T-lymphocytes (CD4-CD8-) contain serotonin and melatonin, immature cortical cells (CD4+CD8+) produce only serotonin, mature medullar cells (CD4+CD8-) show immunoreactivity to serotonin, melatonin, beta-endorphin and histamine. The expression of serotonin, somatostatin and gastrin is localized in thymic epithelial cells, formatting Gassal's bodies. Proliferative activity of thymocytes depends from the expression of serotonin and somatostatin in thymic cells.

CONCLUSION: The data received testify the expression of different hormones in human thymic cells and showing by this fact high endocrine activity of thymus. The presence of correlations between hormonal expression and cell proliferative activity could be considered as the bright illustration of important role of neuroimmunoendocrine mechanisms in the regulation of local thymic homeostasis....

Read abstract

Clinical Trial 2003; 24(3-4): 259-262 PubMed PMID: 14523367 Citation  Keywords:  5-Methoxytryptamine:administration & dosage, Aged, Aged, 80 and over, Antineoplastic Agents:therapeutic use, Antioxidants:administration & dosage, Disease Progression, Female, Humans, Hydroxyindoleacetic Acid:administration & dosage, Indoles:administratio.   

OBJECTIVES: It is known since many years that the pineal gland plays an anticancer role, and melatonin (MLT), the most investigated pineal hormone, has been proven to exert antitumor activity. However, MLT would not be the only hormone responsible for the antitumor action of the pineal gland. In fact, recent advances in the pineal investigations have shown that pineal indoles other than MLT may also exert anticancer activity, namely the three main indoles, consisting of 5-methoxytriptamine (5-MTT), 5-methoxytryptophol (5-MTP) and 5-methoxy-indole acetic acid (5-MIA). Cancer progression has appeared to be associated with a concomitant decline in the pineal endocrine function. Therefore, the replacement of a complete pineal function in the advanced cancer patients would require the exogenous administration of the overall four pineal indoles. Several clinical studies have shown that MLT alone at pharmacological doses may induce a control of the neoplastic progression in about 30% of untreatable metastatic solid tumor patients. The present study was performed in an attempt to evaluate the therapeutic of a total pineal endocrine substitution therapy with its four indole hormones in cancer patients, for whom no other conventional therapy was available.

METHODS: The study included 14 metastatic solid tumor patients, who had failed to respond to the conventional anticancer therapies. The pineal indoles were given orally according to a schedule elaborated in an attempt to reproduce their physiological circadian secretion during the daily photoperiod. MLT was given at 20 mg/day during the night, whereas the other indoles were given at 1 mg/day, by administering 5-MIA in the morning, 5-MTP at noon and 5-MTT in the afternoon.

RESULTS: A disease-control was achieved in 9/14 (64%) patients, consisting of partial response (PR) in one patient and stable disease (SD) in the other 8 patients. The median time of disease-control (PR + SD) was 6 months (range: 4-10).

CONCLUSIONS: This preliminary study shows that a total pineal endocrine replacement therapy by an exogenous administration of the overall four pineal indoles may induce a disease-control in about 60% of untreatable metastatic solid tumor patients. Then, these results would be clearly superior with respect to those described with MLT alone, by confirming in humans that MLT is not the only hormone responsible for the anticancer property of the pineal gland. Since Cartesius was the first author who suggested the fundamental role of the pineal in the connection between consciousness and biological life, this therapy could be defined as a Cartesian therapy....

Read abstract

Clinical Trial 2003; 24(3-4): 255-258 PubMed PMID: 14523366 Citation  Keywords:  Adult, Cross-Sectional Studies, Female, Gastric Emptying:physiology, Graves Disease:physiopathology, Half-Life, Humans, Hyperthyroidism:physiopathology, Kinetics, Male, Radionuclide Imaging, Radiopharmaceuticals, Stomach:diagnostic imaging, Technetium Tc .   

INTRODUCTION AND AIM: About 15% of hyperthyroid patients suffer from gastrointestinal symptoms such as diarrhea, constipation, nausea and early satiety the problem. Published reports on the topic of gastric emptying in hyperthyroidism are rare and discrepant in their results.

PATIENTS AND METHODS: Thirteen patients (8 women, 5 male; aged 41.92+/-1.491 SE yr) with a recently established diagnosis of subclinical hyperthyroidism due to Graves-Basedow disease and as control group 10 age-matched healthy subject (7 women, 3 male; 39.6+/-2.918 SE yrs) participated in this study. Scintigraphic method (food labeled with 99mTc sulfur colloid) was used for measurement of gastric emptying.

RESULTS: Gastric emptying time was similar in both subclinical hyperthyroid and control groups (p=0.413).

DISCUSSION: There are few studies on the subject of gastric emptying in hyperthyroidism with either delayed emptying or with emptying time similar to controls. In the only one study in subclinical hyperthyroidism, gastric emptying was found to be delayed. We also found that gastric emptying was delayed in subclinical hyperthyroidism. On the basis of this and other studies, we may suggest that in subclinical hyperthyroidism, gastric emptying of solids were similar to that in age-matched healthy control subjects and gastrointestinal dysfunction is dependent on severity of the hyperthyroid state and might be a result of impaired neuro-hormonal regulation. Yet the data must be supported on larger groups....

Read abstract