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Journal Article 2002; 23(1): 49-53 PubMed PMID: 11880862 Citation  Keywords:  Aging:physiology, Animals, Circadian Rhythm, Freund's Adjuvant:administration & dosage, Hydroxyindoleacetic Acid:metabolism, Injections, Subcutaneous, Male, Melatonin:metabolism, Norepinephrine:metabolism, Pineal Gland:metabolism, Rats, Rats, Wistar, Sero.   

OBJECTIVES: This study was performed to search for changes in rat pineal function attributed to age and immunization with Freund's adjuvant.

METHODS: Young (2 months) and old (18-20 months) Wistar rats were injected s.c. with Freund's adjuvant or its vehicle. Eighteen days later, at the acute phase of arthritis, pineal concentration of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE) and melatonin was measured by high pressure liquid chromatography at 4 different time intervals throughout the nocturnal activity span.

RESULTS: Old rats had the lowest pineal 5-HT and 5-HIAA content, the decrease in 5-HIAA exceeding that of 5-HT; consequently, old rats had the lowest 5-HIAA/5-HT ratio, an index of pineal 5-HT turnover. Although immunization did not affect globally pineal 5-HT or 5-HIAA levels, significant interactions "immunization x age" and "immunization x time" were found, i.e., immunization augmented pineal 5-HT content at the beginning of the activity span in young rats and at second half of the activity span in young and old rats, and increased pineal 5-HIAA concentration in young rats at the second part of the activity span only. Freund's adjuvant treatment increased pineal 5-HT turnover exclusively in old rats, an effect mainly seen during the second part of the activity span. Old rats exhibited the lowest pineal NE and melatonin levels, immunization further depressing them.

CONCLUSION: The effect of immunization with Freund's adjuvant on a number of pineal pre- and postsynaptic parameters are age-dependent....

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Journal Article 2002; 23(Suppl 3): 11-144 PubMed PMID: 12374906 Citation  Keywords:  Aging:drug effects, Animals, Humans, Oligopeptides:pharmacology, Peptide Hormones:physiology, Peptides:physiology, Pineal Gland:physiology,.   

: A technology has been developed for manufacturing of biologically active complex peptide preparations from extracts of different tissues. In particular, the pineal preparation (Epithalamin) augments the in vitro outgrowth of explants from the pineal gland but not from other tissues, the latter being stimulated by peptide preparations from respective tissues. Epithalamin increases melatonin production by the pineal gland of rats, improves immunological parameters in rats and mice, produces anticarcinogenic effects in different experimental models, stimulates antioxidant defenses, and restores the reproductive function in old rats. These effects are combined in the ability of Epithalamin to increase the lifespan in rats, mice, and fruit flies. Many of these effects are reproduced in clinical trials, which have demonstrated the geroprotector activity of Epithalamin in humans. Among the effects of the thymic preparation Thymalin, those related to its ability to stimulate immunity are the most prominent. This ability is associated with anticarcinogenic and geroprotector activities. Clinical trials of the peptide preparations obtained from other organs including the prostate, the cerebral cortex, and the eye retina, have demonstrated beneficial effects reflected by the improvement of the conditions of respective organs. Based on the data about the amino acid compositions of the peptide preparations, novel principles of the design of biologically active short peptides possessing tissue-specific activities has been developed. Dipeptides specific for the thymus and tetrapeptides specific for the heart, liver, brain cortex, and pineal glands stimulate the in vitro outgrowth of explants of respective organs. Interestingly, for eye retina and the pineal gland, a common tetrapeptide Ala-Glu-Asp-Gly (Epitalon) has been designed, probably reflecting the common embryonal origin of these two organs. Epitalon reproduces the effects of Epithalamin including those related to its geroprotector activity. In particular, Epitalon increases the lifespan of mice and fruit flies and restores the circadian rhythms of melatonin and cortisol production in old rhesus monkeys. At the same time, Epitalon prolongs the functional integrity of the eye retina in Campbell rats with hereditary Retinitis Pigmentosa and improves the visual functions in patients with pigmental retinal degeneration. Changes in gene expression were observed to be produced by the short peptide preparations. Therefore, the effects of Epitalon are suggested to be mediated by transcriptional machinery common for the pineal gland and the retina and, probably, for regulation of melatonin production in fruit flies. Based on three decades of studies of the peptide preparations, the peptide theory of ageing has been put forward. According this theory, ageing is an evolutionary determined biological process of changes in gene expression resulting in impaired synthesis of regulatory and tissue-specific peptides in organs and tissues, which provokes their structural and functional changes and the development of diseases. Correspondingly, correction of such disorders by means of stimulation of peptide production in the organism or through their delivery can promote the normalisation of disturbed body functions....

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Journal Article 2001; 22(5): 337-341 PubMed PMID: 11600875 Citation  Keywords:  Aging, Animals, Apoptosis, Cell Count, Cell Division, Duodenum, Epithelial Cells, Gastric Mucosa:cytology, Histocytochemistry, Immunohistochemistry, Intestinal Mucosa:cytology, Male, Melatonin:biosynthesis, Mice, Mice, Inbred BALB C, Mice, Nude, Neurosecr.   

OBJECTIVES: Diffuse neuroendocrine system (DNES) cells regulate homeostasis via neurocrine, endocrine and paracrine mechanisms. Extensive effects of peptide hormones and biogenic amines necessitate studying of DNES cell biology in aging. In this connection, the functional morphology of gut neuroendocrine cells (NEC), proliferative activity and apoptosis of mucous epithelial cells in aging have been studied.

MATERIAL AND METHODS: The study was performed on BALB/c-nu mice of 4, 21 and 34 months of age. NEC, proliferative activity and apoptosis of mucous epitheliocytes in stomach and duodenum have been studied by histochemical, immunohistochemical and morphometrical methods.

RESULTS: The total number of NEC shows an increasing trend with advancing age. However, the different types of NEC elicit differential patterns. The total number of epithelial cell nuclei does not show any statistically significant difference during aging. The proliferative activity of mucous epitheliocytes also shows no difference among the three animal groups studied. On the contrary, the apoptotic index increases with advancing age.

CONCLUSIONS: The results demonstrate that various gut NEC show differential behavior with age and their time-courses are dependent on the site of location (stomach or duodenum). The picture seems quite complex to allow a comprehensive interpretation, nonetheless it gives us some useful indications for further investigation. In fact, since the gut does not show evident gross age-related physiological changes, modifications with age in specific biological parameters can suggest the key mechanisms of compensative regulatory processes possibly acting during aging....

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Case Reports 2001; 22(4): 263-269 PubMed PMID: 11524634 Citation  Keywords:  Adolescent, Adult, Child, Choristoma:diagnostic imaging, Female, Hormones:therapeutic use, Humans, Hyoid Bone, Mandibular Diseases:drug therapy, Middle Aged, Thyroid Gland, Tomography, X-Ray Computed, Tongue Diseases:diagnostic imaging,.   

OBJECTIVES: The authors describe the classification of heterotopic thyroid tissue. A survey of more than 600 literature cases is provided. Different therapy approaches for these anomalies are discussed. Data from seven subsequent cases have been added to the existing literature data. The authors present an alternative approach to the therapy of heterotopic thyroid tissue.

MATERIALS AND METHODS: The records of seven patients treated for a heterotopy of the thyroid tissue as the Department of ENT and Head and Neck Surgery of First Medical school of the Charles University of Prague since 1.1.1991 to 1.1.2001 have been analyzed.

RESULTS: The first group: No surgery. This approach was used for children. In these patients the heterotopic thyroid tissue is the only thyroid tissue they have, but its function is not damaged and there are no mechanical symptoms (no airway obstruction and dysphagia). TSH substitution-suppression therapy is necessary for this group. Cooperation and follow up by the endocrinology, otolaryngology and pediatric departments is necessary. At a later age these patients can be treated as in the second group. The second group: Surgery. All patients in this group had heterotopic thyroid tissue. The total removal of thyroid tissue has been preferred. Carcinomatous change or the development of mechanical syndrome, dysphagia or airway obstruction is possible. Total removal is the best surgical approach. Various surgical methods are described in the literature (CO2 laser, intraoral, mandibulotomy, middle hyotomy etc.). These patients are treated as after total thyroidectomy and substitution therapy with synthetic thyroid hormones is necessary. The authors describe and add seven cases to the literature data. The authors describe radical removal of aberrant and accessory tissue [corrected]....

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Journal Article 2001; 22(4): 251-254 PubMed PMID: 11524632 Citation  Keywords:  Aging:physiology, Animals, Circadian Rhythm, Endocrine System Diseases:drug therapy, Female, Macaca mulatta, Melatonin:blood, Nervous System Diseases:drug therapy, Oligopeptides:therapeutic use, Osmolar Concentration,.   

UNLABELLED: The OBJECTIVE of this research was to investigate the regulatory effect of Epitalon on the production of melatonin and cortisol in senescent monkeys.

MATERIAL AND METHODS: We investigated the character of melatonin and cortisol secretion by immunoferment assay in Epitalon-administered female Macaca mulatta in different age periods.

RESULTS: Epitalon was proven to significantly stimulate melatonin synthesis in senescent monkeys in the evening, thereby normalising the circadian rhythm of cortisol secretion....

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Journal Article 2001; 22(3): 163-168 PubMed PMID: 11449190 Citation  Keywords:  Aged, Aged, 80 and over, Aging, Alzheimer Disease:blood, Case-Control Studies, Cross-Sectional Studies, Female, Humans, Linear Models, Male, Memory, Middle Aged, Reference Values, Testosterone:blood,.   

OBJECTIVES: The purpose of this study was to determine whether the level of serum total testosterone (TT) was different in cases of Dementia of the Alzheimer's Type (DAT) than in controls.

SETTING AND DESIGN: We included 83 referred DAT cases and 103 cognitively screened volunteers (aged 75+/-9 years) from the Oxford Project To Investigate Memory and Ageing.

METHODS: Information was obtained about potential confounds in the relation of DAT with testosterone, including age, gender, education, body mass index, smoking, (ab)use of alcohol, diabetes mellitus, endocrine therapy, and having undergone hysterectomy. TT was measured in non-fasting serum obtained between 10 and 12 a.m. using a competitive enzyme immunoassay.

RESULTS: Men with DAT (n=39) had lower levels (p =0.005) of total serum testosterone (TT=14+/-5 nmol/L) than controls (n=41, TT=18+/-6 nmol/L). Lower TT was more likely in men with DAT, independent of potential confounds (Odds Ratio=0.78, 95% C.I.=0.68 to 0.91). In women there was no difference in TT levels between cases (n=44) and controls (n=62).

MAIN FINDINGS: Our results suggested that low TT may be a co-morbid feature of DAT in men. However, low TT levels could also exacerbate the disease.

CONCLUSIONS: Prospective longitudinal studies should investigate whether low TT levels precede or follow the onset of DAT (209 words)....

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Journal Article 2001; 22(1): 9-18 PubMed PMID: 11335874 Citation  Keywords:  Adult, Aged, Aged, 80 and over, Aging:drug effects, Animals, Antioxidants:metabolism, Catalase:drug effects, Drosophila melanogaster, Free Radicals:metabolism, Humans, Lipid Peroxidation:drug effects, Melatonin:metabolism, Middle Aged, Oxidation-Reduction.   

OBJECTIVES: The review on our own data on the effect of the pineal peptide preparation Epithalamin on free radical processes in rodents and humans is presented in this paper.

RESULTS: The activity of Cu, Zn-superoxide dismutase (SOD) was found decreased in the brain of aged rats (30 months old) by 46.8% as compared to young animals. Concentration of Schiff's bases in the brain also went down with age (by 13.6%), while the level of dien conjugates (DC) and protein peroxidation (PPO) remained unchanged. General antioxidation activity (AOA) in the brain also remained stable with age. The liver of aged rats showed significant increase of Schiff's bases (by 27.1%) and PPO products (by 109.2%) and considerable decrease of SOD activity. The level of DC and general AOA in the liver remained unchanged with age. Considerable elevation of protein and lipid peroxidation products contents was registered in the blood serum of aged rats. At the same time, general AOA and SOD activity remarkably decreased. The results obtained evidence from both significant age-related alterations in the activity of free radical processes in animal organism and organic peculiarities of their dynamics. Application of peptide drug epithalamin suppressed significantly the intensity of peroxide chemoluminescence in the blood serum (2.8-fold) and lipid peroxide oxidation (LPO) expressed in the considerably decreased DC contents (4,1-fold). The contents of Schiff's bases showed only a tendency towards decrease (by 14.4%, p > 0.05) and PPO level remained unchanged. Epithalamin administration was followed by considerable (by 36.6%, p < 0.01) increase of general AOA and increased SOD activity (by 19.7%) in males. Epithalamin decreased significantly the contents of conjugated hydroperoxides and ketodienes in tissues of D.melanogaster females, increased catalase activity in drosophila males and females, and increased SOD activity in males of D.melanogaster by 41%. Humans reveal significant age-related decrease of antioxidation defence indices.

CONCLUSION: Epithalamin administration to patients with age-related pathology eliminates imbalance in prooxidation and antioxidation systems....

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Case Reports 2018; 39(3): 149-155 PubMed PMID: 30431740 Citation  Keywords:  Adenocarcinoma:diagnostic imaging, Carcinoma, Non-Small-Cell Lung:diagnostic imaging, Duodenal Neoplasms:diagnostic imaging, Gastrointestinal Stromal Tumors:diagnostic imaging, Humans, Lung Neoplasms:diagnostic imaging, Male, Middle Aged, Neoplasms, Multi.   

: Neurofibromatosis type 1 (NF1, von Recklinghausen disease) is inherited in autosomal dominant way genetic disorder, with an incidence at birth 1:3000. It is one of the most common congenital disorders. It is characterized by café-au-lait spots, neurofibromas, and less common MPTST and gliomas of the optic nerve. It is caused by germline mutations of the NF1 gene, which acts as tumor suppressor. Inactivation of the gene leads to increased activation of the kinase pathways, and in consequence, uncontrolled proliferation of cells. The disease predisposes to the development of both benign and malignant tumors. Malignant tumors, but not related to the nervous system occur in neurofibromatosis quite rare. The aim of the study is a literature review of NF1, with presentation of a patient with NF1 and coexisting numerous tumors: synchronous somatostatinoma and gastrointestinal stromal tumor with metachronous prostate adenocarcinoma and non-small cell lung carcinoma. And attempt to answer the question if there is a common pathway for oncogenesis of these four tumors....

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