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Journal Article 2003; 24(5): 314-320 PubMed PMID: 14647003 Citation  Keywords:  Animals, Bone Density, Female, Mandible:diagnostic imaging, Rats, Rats, Wistar, Superior Cervical Ganglion:surgery, Sympathectomy, Tomography, X-Ray Computed, Tooth Eruption:physiology,.   

OBJECTIVE: To assess the effect of local sympathectomy on mandibular bone during tooth eruption in rats.r />r /> METHODS: The effect of a unilateral superior cervical ganglionectomy (Gx) on morphometry of ipsi- and contralateral mandible and volumetric bone density (as assessed by peripheral computed tomography) was examined 30 days after surgery.r />r /> RESULTS: Only a few mandibular morphometric parameters decreased significantly after denervation in rats subjected to a unilateral Gx and a contralateral sham-operation. Mandibular volumetric bone density decreased significantly after sympathetic denervation. In a second experiment, carried out under conditions of unilateral unimpeded eruption of incisors performed ipsilaterally or contralaterally to a unilateral Gx, a significant interaction "denervation x type of eruption" was found for most morphometric parameters. Further analysis indicated higher morphometric indexes in denervated mandibles than in the innervated ones under impeded incisor eruption conditions, and lower morphometric indexes in denervated mandibles than in the innervated ones under unimpeded incisor eruption conditions. Unimpeded eruption augmented total volumetric bone density providing the innervation was intact and caused opposite effects on cortical volumetric bone density in the presence of innervation (increase) or absence of innervation (decrease). Trabecular volumetric bone density decreased significantly after sympathetic denervation.r />r /> CONCLUSION: The results support a role of the sympathetic nervous system in the regulation of bone remodeling....

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Journal Article 2003; 24(5): 310-313 PubMed PMID: 14647002 Citation  Keywords:  Animals, Antioxidants:pharmacology, Circadian Rhythm, Cyclin-Dependent Kinase Inhibitor p21, Cyclins:metabolism, Male, Melatonin:pharmacology, Rats, Rats, Wistar, Thyroid Gland:cytology,.   

OBJECTIVES: The cell-cycle (cc) is, in part, controlled by cyclin-dependent kinases (CDKs), which are activated after binding cyclins (positive regulators of cc). CDK inhibitors (CDKIs), such as p15, p16, p21, and p27, inhibit cyclin-CDK complex activity, and function as negative cell cycle regulators, blocking cell-cycle progression. The aim of our study was to examine the influence of late-afternoon (1600-1800) subcutaneous (s.c.) melatonin (Mel) injections, administered for 2 weeks, on the p21 expression in male Wistar rat thyroid follicular cells (TFC).r />r /> METHODS: In order to detect the anti-p21 antibodies, the DAKO LSAB2 Rat Kit/HRP (DAKO, USA) and DAKO Liquid DAB Substrate-Chromogen System (DAKO, USA) were employed.r />r /> RESULTS: No statistically significant changes of p21(LI) (p21 labelling index) values were observed in particular groups of the rats receiving Mel injections, in comparison to the controls. The statistical difference of p21(LI) values (p<0.03) was only observed between groups of rats, receiving Mel injections in the dose of 25 microg/daily and 100 microg/daily.r />r /> CONCLUSION: Melatonin - in the applied doses and in the experimental conditions without any factors revealing anti-DNA activity - did not change, in any statistical way, p21 expression in rat thyroid follicular cells, as compared to the control group....

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Journal Article 2003; 24(5): 304-309 PubMed PMID: 14647001 Citation  Keywords:  Analgesics:pharmacology, Analgesics, Opioid:pharmacology, Animals, Antioxidants:pharmacology, Ascorbic Acid:pharmacology, Aspirin:pharmacology, Drug Therapy, Combination, Free Radicals:metabolism, Lipid Peroxidation:drug effects, Male, Morphine:pharmacolo.   

OBJECTIVES: To study the balance between the pro-oxidative and antioxidative defence system after repeated painful stimulation in rats and the efficacy of the administration of different antioxidants (vitamins C, E, A, and selenium), analgesics (acetylsalicylic acid, morphine), and their combinations.r />r /> METHODS: Mechanical clamping of both hind limbs was applied for 10 min for 5 consecutive days in adult male Wistar rats. The tail-flick latency was measured before and after a 5-day nociceptive stimulation with or without the substance application. The reactive oxygen species (ROS) were determined in the sensorimotor cortex.r />r /> RESULTS: Painful stimulation increased lipoperoxidation which persisted for up to 15 days after it had been discontinued. A simultaneous injection of antioxidants decreased the levels of TBARS, SOD and GSHPx; however, antioxidants applied one week prior to the painful stimulation were ineffective. A simultaneous injection of analgesics reduced stress-induced analgesia caused by the nociceptive stimulation, but did not affect lipoperoxidation.r />r /> CONCLUSIONS: A combination of antioxidants with analgesics normalized both the oxidative stress and functional (the tail-flick latency) indicators. These results suggest that the administration of antioxidants in pain treatment may be employed to decrease the doses of analgesics and to prevent the negative impact of reactive oxygen species on nociception....

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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....

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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.r />r /> 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.r />r /> 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.r />r /> 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....

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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.r />r /> 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.r />r /> 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.r />r /> 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....

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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.r />r /> 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.r />r /> 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.r />r /> 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....

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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.r />r /> 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.r />r /> 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).r />r /> 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....

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