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Clinical Trial 2003; 24(1-2): 77-82 PubMed PMID: 12743538 Citation  Keywords:  Aged, Area Under Curve, Circadian Rhythm:physiology, Female, Hormones:blood, Humans, Lung Neoplasms:blood, Male, Neurosecretory Systems:physiopathology,.   

BACKGROUND: A number of qualitative and quantitative changes in hormonal secretion pattern have been found in subjects suffering from neoplastic disease. The aim of this study was to evaluate the presence of alterations in neuro-endocrine system function and in the pattern of endocrine secretion in patients with lung cancer.

METHODS: Cortisol, melatonin, growth hormone (GH), insulin-like growth factor I (IGF-I), thyrotropin-releasing hormone (TRH), thyroid-stimulating-hormone (TSH), and free thyroxine (FT4) serum levels were measured on blood samples collected every four hours for 24 hours from ten healthy old subjects aged 65-79 years (mean age +/- s.e. 67.28 +/- 3.11) and from ten subjects suffering from untreated non small cell lung cancer aged 65-78 years (mean age +/- s.e. 68.57 +/- 1.81). Areas under the curve and mean diurnal and nocturnal levels were compared and the presence of circadian rhythmicity was evaluated.

RESULTS: When hormone levels were expressed as area under the curve GH levels were higher (p=0.004) and IGF-I levels were lower (p=0.006) in patients with lung cancer than in normal subjects. The evaluation of melatonin/cortisol ratio in all subjects showed a significant difference between the control group and the group of cancer patients (p<0.05). When we compared mean diurnal levels (mean of 06.00-10.00-14.00h) GH levels were higher (p<0.0001) and IGF I levels were lower (p<0.0001) in cancer patients; when we compared mean nocturnal levels (mean of 18.00-22.00-02.00h) cortisol (p=0.03), TRH (p=0.02), and GH (p=0.001) levels were higher in cancer patients, while melatonin (p=0.04), TSH (p=0.04) and IGF I (p<0.0001) levels were higher in control subjects. A clear circadian rhythm was validated for time related changes of cortisol, melatonin, TRH, TSH and GH in control subjects and for time related changes of melatonin in cancer patients.

CONCLUSION: These data suggest that lung cancer patients show alterations of hormone secretion and neuroendocrine system function....

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Clinical Trial 2003; 24(1-2): 50-53 PubMed PMID: 12743532 Citation  Keywords:  Adult, Apomorphine:pharmacology, Disease Progression, Human Growth Hormone:blood, Humans, Hydrocortisone:blood, Male, Neoplasm Metastasis, Neoplasms:physiopathology, Neurosecretory Systems:drug effects, Prolactin:blood,.   

OBJECTIVES: The clinical approach of the Psychooncology is generally limited to the investigation of the only psychological status of cancer patients, without taking into consideration the well demonstrated cancer progression-related psychoneuroendocrine alterations, namely consisting of a progressive decline in the pineal endocrine function and an anomalous activity of brain opioid system. The endocrine response to apomorphine, a dopaminergic agent, has been proven to reflect the dopaminergic sensitivity, which would be involved at least in part in pleasure-related neurochemical mechanisms. The present study was performed to analyze the endocrine response to apomorphine in metastatic cancer patients, as a preliminary approach to the investigation of pleasure-related neuroendocrine mechanisms in human neoplasms.

MATERIALS & METHODS: The study included 10 metastatic cancer male patients and 6 male volunteers as a control group. Apomorphine was given orally at 0.01 mg/kg body weight in the morning, and venous blood samples were collected before, and at 20, 60 and 120 minutes after apomorphine administration. The endocrine analysis consisted of the measurement of serum levels of GH, PRL and cortisol.

RESULTS: All cancer patients presented alterations involving one or more endocrine responses to apomorphine. GH and cortisol mean levels after apomorphine were significantly higher in controls than in cancer patients, whereas no substantial difference occurred in those of PRL.

CONCLUSIONS: This preliminary study, by showing an altered endocrine response to apomorphine in metastatic cancer patients, would suggest that cancer progression may be associated with an altered dopaminergic sensitivity. Because of the involvement of the dopaminergic system in pleasure-related neurochemical mechanisms, this finding would demonstrated that the decline in the perception of pleasure with cancer progression may depend not only on psychological factors, but also, at least in part, on psychochemical alterations occurring during the clinical course of the neoplastic disease....

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Journal Article 2002; 23(5-6): 447-451 PubMed PMID: 12500170 Citation  Keywords:  Animals, Cell Differentiation:physiology, Gene Expression Regulation:physiology, Humans, Immune System:physiology, Neuroendocrine Tumors:metabolism, Neuronal Plasticity:physiology, Neuropeptides:metabolism, Neurosecretory Systems:cytology,.   

: The term neuroendocrine has been used to define cells that secrete their products in a regulated manner, in response to a specific stimulus. The neuroendocrine system includes neurons and endocrine cells sharing a common phenotypic program characterized by the expression of markers such as neuropeptides, chromogranins, neuropeptide processing enzymes SPC2 and SPC3 (subtilase-like pro-protein convertases) or dense core secretory granules. Various theories such as the APUD (amine precursor uptake decarboxylation) concept, the diffuse neuroendocrine system (DNES) or the paraneuron concept have been put forth to classify neuroendocrine cells as a cohesive group. Neuroendocrine characteristics have been used as evidence of a common embryological origin for normal and neoplastic cells. However, it is now recognized that neuroendocrine characteristics can be observed in various cell types, such as immunocytes, that are not of a common embryological origin with either neurons or endocrine cells. We propose to redefine previous "neuroendocrine" concepts to include the notion that activation of specific genetic switches can lead to the expression of a partial or full neuroendocrine phenotype in a variety of cell types, including immune cells....

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Journal Article 2002; 23(5-6): 443-446 PubMed PMID: 12500169 Citation  Keywords:  Animals, Cell Nucleus:ultrastructure, Cell Size:physiology, Cricetinae, Endoplasmic Reticulum, Rough:ultrastructure, Female, Ganglionectomy, Glycogen, Golgi Apparatus:ultrastructure, Lysosomes:ultrastructure, Mitochondria:ultrastructure, Organelles:ultras.   

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....

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Journal Article 2002; 23(5-6): 405-410 PubMed PMID: 12500161 Citation  Keywords:  Animals, Endoplasmic Reticulum, Rough:ultrastructure, Estradiol:analogs & derivatives, Female, Hormone Replacement Therapy, Microscopy, Electron, Mitochondria:drug effects, Ovariectomy, Pineal Gland:drug effects, Rats, Rats, Wistar, Ribosomes:drug effects.   

OBJECTIVE: The aim of this study was to examine the effects of ovariectomy and ovariectomy followed by estradiol benzoate administration on the ultrastructure of pinealocytes in female rat.

DESIGN: For this purpose 15 female Wistar rats were used. Animals were divided into three groups. Group I and II were designated as sham-ovariectomized (control) and ovariectomized, respectively. Group III was ovariectomized and daily injected with estradiol benzoate for one month. At the end of the experiment, all animals were anesthetized with ketamine for fixation by vascular perfusion. Pineal glands of groups I, II and III were removed. All specimens were examined by electron microscopy.

RESULTS: Ovariectomy caused an increase of lipid droplets, mitochondria and ribosomes. Rough endoplasmic reticulum was extensive in the cytoplasm. Estradiol administration to ovariectomized rats resulted in formation of less extensive lipid droplets, mitochondria and ribosomes compared to pinealocyte ultrastructure of both control and ovariectomized rats. Extensiveness of rough endoplasmic reticulum in the pinealocytes of estradiol-administrated rats was similar to that in controls.

CONCLUSIONS: The results confirm relationship between the pineal gland and gonads in the rat and it has been suggested that estradiol benzoate reverses the ultrastructural changes, which indicate increased cell activation, occurring in the pinealocytes after ovariectomy....

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Clinical Trial 2002; 23(4): 365-368 PubMed PMID: 12195242 Citation  Keywords:  Adolescent, Adult, Aged, Animals, Electric Conductivity, Electroretinography, Humans, Middle Aged, Oligopeptides:administration & dosage, Pineal Gland:drug effects, Rats, Rats, Inbred Strains, Retina:pathology, Retinitis Pigmentosa:drug therapy,.   

: We have studied the effect of tetrapeptide Epitalon (Ala-Glu-Asp-Gly) on the course of congenital pigmented degeneration of the retina. The application of Epitalon in Campbell rats is found to intensify the bioelectric and functional activity of the retina due to the preservation of its morphological structure. Epitalon therapy in patients with degenerative retinal lesions results in a positive clinical effect in 90% of the cases. The analysis of Epitalon effects suggests that the tetrapeptide participates in the mechanisms of transcription common for the epiphysis and retina....

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Journal Article 2002; 23(4): 281-285 PubMed PMID: 12195225 Citation  Keywords:  Anti-Inflammatory Agents, Non-Steroidal:adverse effects, Aspirin:adverse effects, Asthma:chemically induced, Humans, Neurosecretory Systems:pathology,.   

: Available clinical data on aspirin-sensitive asthma (ASA) indicate that ASA patients have certain disturbances in the nervous, endocrine, immune and other body systems. It has been found that such patients have a lower melatonin (MT) production in daytime, a pathology of the platelet membrane-receptor complex, and a pathological response to exogenic MT and acetylsalicylic acid. A hypothesis has been suggested in which ASA is considered as apudopathy caused by dysfunction of MT-producing cells. The decreased MT production and the disturbed cell sensitivity to MT lead to pathological changes in individual organs and functional systems. As a result, there is an enhanced lipid peroxidation, an excessive production of reactive oxygen radicals, and a reduced inhibitory action of MT on the 5-lipoxygenase and NO-synthase activities. The lower MT content also results in an intense aggregation of platelets, activating these cells and increasing the production of leukotrienes and nitric oxide. These changes disturb the pulmonary microcirculation, causing the bronchial obturation syndrome even in patient who do not take aspirin or other nonsteroidal anti-inflammatory drugs. The lower basic production of MT is also responsible for a lower content of its metabolite-endogenic acetylsalicylic acid, thereby increasing the sensitivity of melatonin-producing cells, in particular of platelets, to this acid. So, even minimal aspirin doses inhibit the activity of COX-1, which shunts the already abnormal metabolism of arachidonic acid. This, in turn, leads to a greater production of leukotrienes and, hence, to a severe course of the disease. This hypothesis has become the basis for a new pathogenetic approach to the treatment of ASA patients by correcting the melatonin content with peptide bioregulators--the epiphysis extracts--Epithalamin and Epiphamin....

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Congresses 2002; 23(Suppl 2): 84-87 PubMed PMID: 12163855 Citation  Keywords:  Animals, Humans, Light:adverse effects, Neoplasms:epidemiology, Neurosecretory Systems:physiology, Risk Factors,.   

: The International Symposium "Light, Endocrine Systems and Cancer" was held on May 2-3 at Cologne University, Germany. The symposium was organized by Professor Claus Piekarski and Dr. Thomas C. Erren, Institute and Polyclinic for Occupational and Social Medicine. The main goal of the symposium was to evaluate the epidemiological and experimental data on the effect of the exposure to light-at-night on cancer risk and to indicate the main directions of future research in the field. The symposium covered also the mechanisms and epidemiology of skin cancer which, however, are not included in the present summary....

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