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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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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....

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Journal Article 2003; 24(3-4): 170-172 PubMed PMID: 14523352 Citation  Keywords:  Animals, Antioxidants:therapeutic use, Male, Malondialdehyde:blood, Melatonin:therapeutic use, Rats, Rats, Sprague-Dawley, Reperfusion Injury:pathology, Spermatic Cord Torsion:pathology, Testicular Diseases:pathology, Testis:metabolism,.   

AIM: Torsion of testis, which is a urologic emergency case, is generally treated by surgical detorsion procedure. However, the resulting reperfusion and both ipsilateral and contralateral testis damage caused thereby are important problems. This study aims at investigating the administration of prophylactic melatonin in order to reduce free radical damage that is caused due to reperfusion after experimental testis torsion-detorsion procedure.

MATERIAL AND METHOD: The rats used in the study were allocated to four groups, each containing 10 rats. Rats in Group I had six hours of torsion (ischemia) followed by orchiectomy. Rats in Group II had six hours of torsion, then received melatonin (10 mg/kg/IM) and after that had detorsion (reperfusion). Rats in Group III had detorsion after six hours of torsion and serum physiologic administration (the same volume as melatonin). Torsion and/or detorsion procedures were not applied in Group IV (control). Ipsilateral, contralateral testis and plasma Malondialdehyde (MDA) levels were determined in all groups.

RESULTS: Tissue and plasma MDA levels in the group which had detorsion were found to be significantly higher than those in the group that had orchiectomy only (p<0.02). Ipsilateral and contralateral testis MDA levels were identified to be significantly lower in the group receiving prophylactic melatonin in comparison to the group receiving serum physiologic (p<0.02). Plasma and contralateral MDA levels correlated positively with MDA levels identified in ipsilateral testis in all groups (rs=+0.89, n=40, p=0.000).

CONCLUSION: In cases where testis torsion is identified, administration of melatonin just before torsion may reduce local and systemic free radical damage....

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Journal Article 2003; 24(1-2): 86-90 PubMed PMID: 12743540 Citation  Keywords:  Animals, Antioxidants:metabolism, Glutathione Peroxidase:metabolism, Male, Malondialdehyde:metabolism, Melatonin:pharmacology, Nitric Oxide:metabolism, Rats, Rats, Wistar, Superoxide Dismutase:metabolism, Testis:drug effects, Varicocele:metabolism,.   

OBJECTIVES: The pathophysiology of the testicular damage in varicocele have not been completely understood. There are several studies concerning the effects of increased seminal reactive oxygen species (ROS) and the role of nitric oxide (NO) in infertile patients with varicocele and antioxidants have been used successfully to decrease oxidative stress in testis. In this study, we determined the effects of melatonin on testicular NO and antioxidant enzyme levels and investigated whether melatonin can prevent or diminish testicular damage in adult rats with experimentally induced unilateral varicocele.

METHODS: Thirty adult male Wistar rats were randomly divided into three groups. In group I, using midline incision left renal vein was exposed but not tied. In group II, left renal vein was partially ligated to create varicocele. In group III, after creation of varicocele, daily and fresh-prepared melatonin was administered intraperitoneally for 4 weeks. Histopathological examination was performed and tissue malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and tissue NO levels were determined.

RESULTS: In group II, there were severe degenerative changes of the germinal epithelium and atrophy of the seminiferous tubules in left testis. In group III, in which rats received melatonin intraperitoneally, there were focal areas showing decrease in spermatogenesis and some degenerative changes. Similarly, the levels of ROS and NO were significantly increased in testicular tissue of rats in group II, whereas group III rat testes in which melatonin was administered, showed increased antioxidant enzyme activity and decreased NO levels.

CONCLUSION: Infertility related to varicocele has multiple pathophysiological mechanisms and the effect of ROS, NO and antioxidant defense system are contributing factors in the disease state. Melatonin, a potent free radical scavenger, administration might be helpful in the prevention or at least, in the delay of the severe effects of varicocele on testicular tissue....

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Journal Article 2003; 24(1-2): 68-72 PubMed PMID: 12743536 Citation  Keywords:  Animals, Bivalvia:metabolism, Cold Temperature:adverse effects, Down-Regulation, Ganglia, Invertebrate:metabolism, Nitric Oxide:biosynthesis, RNA:analysis, Receptors, Opioid, mu:biosynthesis, Reverse Transcriptase Polymerase Chain Reaction, Stress, Physio.   

OBJECTIVES: Subjecting the marine bivalve Mytilus edulis to an immediate temperature change has been shown to rapidly alter the animals' ganglionic monoamine levels, as well as its ciliary activity. Recently, we extended this observation to include the organism's ganglionic mu opiate receptor and morphine levels. In the past, we demonstrated that M. edulis ganglionic mu receptors exposed to morphine was coupled to the immediate release nitric oxide (NO). In this study, we measured morphine-induced NO release in M. edulis subjected to acute cold stress.

METHODS: NO release was monitored with an NO-selective microprobe. Temporal changes in mu opiate receptor expression were also examined over 24 hours.

RESULTS: In this study, we demonstrate that after 12h cold exposure (4 degrees C from 24 degrees C), the estimated relative mu opiate receptor (MOR) gene expression in M. edulis pedal ganglia, measured by real-time PCR, did not differ significantly from the control group (1.23+/-0.25, p>0.05). However, the measured M. edulis pedal ganglia MOR expression demonstrated that ganglia significantly (0.77+/-0.05, p<0.001) down regulated their mu opiate receptor mRNA expression after 24h exposure to the cold water. The mean value for control animal (24 degrees C, n=14) morphine-stimulated NO release was 36.7 +/- 9.8 nM. Morphine additions to cold-treated tissues (4 degrees C, n=7) produced an average of 6.7 +/- 4.9 nM NO, which was a statistically significant difference between 25 degrees C and 4 degrees C animals (p=0.025).

CONCLUSION: The study further demonstrates that mu opiate receptor expression is coupled to NO release....

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Journal Article 2002; 23(5-6): 459-482 PubMed PMID: 12500173 Citation  Keywords:  Adult, Aged, Aged, 80 and over, Antioxidants:therapeutic use, Causality, Chronic Disease, Cognition Disorders:epidemiology, Comorbidity, Dental Amalgam:adverse effects, Dental Restoration, Permanent:adverse effects, Dentistry, Operative, Depression:epidem.   

OBJECTIVES: The purpose of this study was to evaluate treatment of patients suffering from chronic ill health with a multitude of symptoms associated with metal exposure from dental amalgam and other metal alloys.

SETTING AND DESIGN: We included 796 patients in a retrospective study using a questionnaire about symptom changes, changes in quality of life as a consequence of treatment and assessment of care taking.

METHODS: Treatment of the patients by removal of offending dental metals and concomitant antioxidant therapy was implemented according to the Uppsala model based on a close co-operation between physicians and dentists.

RESULTS: More than 70% of the responders, remaining after exclusion of those who had not begun or completed removal, reported substantial recovery and increased quality of life. Comparison with similar studies showed accordance of the main results. Plasma concentrations of mercury before and after treatment supported the metal exposure to be causative for the ill health.

MAIN FINDINGS: Treatment according to the Uppsala model proved to be adequate for more than 70% of the patients. Patients with a high probability to respond successfully to current therapy might be detected by symptom profiles before treatment.

CONCLUSIONS: The hypothesis that metal exposure from dental amalgam can cause ill health in a susceptible part of the exposed population was supported. Further research is warranted to develop laboratory tests to support identification of the group of patients responding to current therapy as well as to find out causes of problems in the group with no or negative results....

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Case Reports 2002; 23(5-6): 387-390 PubMed PMID: 12500158 Citation  Keywords:  Analgesics, Non-Narcotic:therapeutic use, Anti-Anxiety Agents:therapeutic use, Anticonvulsants:therapeutic use, Antioxidants:therapeutic use, Benzodiazepines, Child, Preschool, Consanguinity, Disease Progression, Dronabinol:therapeutic use, Electroencepha.   

GOAL: The casuistic of a child suffering from late infantile neuronal ceroid lipofuscinosis (NCL) of the type Jansky-Bielschowsky aims to provide a description of possible therapeutic options for the severe spastic and the debilitating myocloni that occur within the context of this disorder. Moreover, it also should include a discussion of potential indications for the application of delta 9-Tetrahydrocannabinol (THC) (Dronabinol, Marinol) in childhood....

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Comparative Study 2002; 23(4): 345-350 PubMed PMID: 12195239 Citation  Keywords:  Aging:metabolism, Animals, Antioxidants:metabolism, Darkness, Hippocampus:enzymology, Lighting, Lipid Peroxidation:physiology, Male, Pineal Gland:physiology, Rats, Rats, Wistar, Receptors, N-Methyl-D-Aspartate:metabolism, Superoxide Dismutase:metabolism,.   

OBJECTIVES: To investigate the effects of pinealectomy on lipid peroxidation, antioxidant status and NMDA receptor subunits 2A and 2B concentrations in hippocampus.

DESIGN: Forty-eight male Wistar-albino rats were used.

SETTINGS: Animals were divided into three groups: 24 h dark throughout the study (highest melatonin release), 24 h light exposure (light-induced functional pinealectomy) and 12 h light/12 h dark exposure (control group). Thereafter, each group was divided into two groups as young and old animals.

RESULTS: There was an increase in NR2A and NR2B concentration in DY group compared to all other treatments. CuZn and Mn SOD activities were found to be increased in CO compared to CY group. Continual light exposure for 4 weeks did not change neural CuZn and Mn SOD activities. In old rats, light exposure reduced the activities of both CuZn and Mn SOD relative to those in the young animals. In addition, CuZn and Mn SOD activities were higher in dark exposed rats than in those in the continual light exposed or LD 12:12 rats. GSH-Px activity was found elevated in the DY rats compared to the CY groups. MDA levels were significantly higher in the CO than in the CY group.

CONCLUSIONS: NR2A and NR2B receptor concentrations in hippocampus of the rats maintained in dark showed significant increases compared to the control and functional pinealectomy groups but there was no significant increase in lipid peroxidation....

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