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Case Reports 2002; 23(4): 370-372 PubMed PMID: 12195243 Citation  Keywords:  Aged, Aged, 80 and over, Female, Fluorescein Angiography, Humans, Macular Degeneration:diagnosis, Photochemotherapy, Photosensitizing Agents:administration & dosage, Porphyrins:administration & dosage,.   

: Our controlled case describes the drug possibility to stabilize the exudative form of Age-related Macular Degeneration. The new approach of selective destruction of choroidal neovascularization (CNV) can be applied in patients with subfoveal lesions. Photodynamic therapy (PDT) is based on the reaction of photoactivable drug with the light of low-energy laser beam. So far only verteporfin [Visudyne, Novartis] as sensitizer is marketed and laser with wavelength of 689 nm is used. But it is questionable whether to apply this very costly treatment to extremely old people. An example of treatment of 90-year old woman with AMD with classic form of CNV is presented. Her BCVA was 0.05 OD. She underwent four session of PDT. At the last visit (eighteen months after initial and ten months after last session of PDT) the BCVA remained 0.05 OD. The patient is using a special magnifying lens for reading achieving near vision of 0.32. The presented example indicates the necessity of detailed study of every case to promote the therapeutic decisions for the benefit of progress in the field....

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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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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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Clinical Trial 2002; 23(4): 341-344 PubMed PMID: 12195238 Citation  Keywords:  Adjuvants, Immunologic:administration & dosage, Aged, Antineoplastic Agents:administration & dosage, Carcinoma, Neuroendocrine:drug therapy, Carcinoma, Renal Cell:drug therapy, Digestive System Neoplasms:drug therapy, Female, Humans, Injections, Subcutane.   

OBJECTIVES: The preliminary applications of the psychoneuroimmunological knowledges to the treatment of human diseases have confirmed the possibility to amplify IL-2-dependent anticancer immunity by the pineal hormone melatonin (MLT) or by opioid antagonist, such as naltrexone (NTX), which act by activating TH1 lymphocytes or suppressing TH2 lymphocytes, respectively. At present, however, there are no data about the immunobiological effects of a concomitant administration of both MLT and NTX on IL-2-induced anticancer immunity. This preliminary study was carried out to evaluate whether the association of NTX may further enhance the lymphocytosis induced by the neuroimmunotherapy with IL-2 plus MLT.

MATERIALS & METHODS: The study included 14 consecutive untreatable metastatic solid tumor patients. According to a cross-over randomized study, the patients were treated during two consecutive immunotherapeutic cycles at 21-day intervals with IL-2 plus MLT alone or with IL-2 plus MLT plus NTX. IL-2 was injected subcutaneously at 3 MIU/day for 6 days/week for 4 weeks, MLT was given orally at 20 mg /day in the evening every day, and NTX was given orally at 100 mg in the morning every next day. For the immune evaluation, venous blood samples were drawn before the onset of treatment and at weekly intervals.

RESULTS: Lymphocyte mean number significantly increased after both IL-2 plus MLT and IL-2 plus MLT plus NTX. However, the concomitant administration of NTX induced a significantly higher increase in lymphocyte mean number with respect to that achieved with IL-2 plus MLT alone. In contrast, the increase in eosinophil mean number was significantly higher on IL-2 plus MLT alone.

CONCLUSIONS: This preliminary study shows that the association of NTX further amplifies the lymphocytosis obtained by IL-2 plus MLT. Since the lymphocytosis represents the most important favourable prognostic variable predicting the anticancer efficacy of IL-2 immunotherapy, it is probable that a cancer neuroimmunotherapy with IL-2 plus both MLT and NTX to activate TH1 and suppress TH2 cells respectively, may deserve more promising results in the treatment of human neoplasms according to the psychoneuroimnunological knowledge....

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Journal Article 2002; 23(4): 335-340 PubMed PMID: 12195237 Citation  Keywords:  Animals, Anticonvulsants:pharmacology, Cell Division:drug effects, DNA:biosynthesis, Drug Interactions, Hepatocytes:drug effects, Male, Melatonin:pharmacology, Mutagens:pharmacology, Necrosis, Nitroparaffins:pharmacology, Propane:analogs & derivatives, Ra.   

OBJECTIVES: 2-Nitropropane (2-NP) is mutagenic in a number of short-term mutagenicity assays in vitro and in vivo, and is a potent hepatocarcinogen in rats. Many studies have determined that differences in the metabolism and disposition of the chemicals that produce mutagenicity were not responsible for their observed carcinogenic differences, but that carcinogenicity correlated with the ability of the respective isomer to induce cell proliferation in the target organ.

METHODS: Three groups of male rats (control, 2-NP-treated [4 mmol/kg] and 2-NP + melatonin [10 mg/kg]) were used in the current study. Cell proliferation was quantitated by incorporation of 3H-thymidine, detected by autoradiography, into newly synthesized DNA. Histopatholgical study was carried out to investigate the morphological changes.

RESULTS: Twenty four hours after 2-NP administration, there was an increase in the labelling index (LI) and grain count per labelled nucleus (GC/N) in the hepatocytes of 2-NP-injected rats versus those of control animals. The increase was 69.5% in LI and 29.4% in GC/N. Melatonin treatment, 30 minutes preceding 2-NP, reduced the increase in LI (44.4%) and GC/N (20.7%) when compared with 2-NP-treated rats. Histopathology revealed multiple focal areas of necrosis in the liver following 2-NP injection. In the lung, there was a mucinous degeneration of the bronchial epithelium. Melatonin treatment restored the histopathological changes in both the liver and lung and they are more or less normal.

CONCLUSION: Overall, these results seem to indicate that the stimulatory effect of 2-NP on the cellular proliferation and the rate of DNA synthesis in the liver may be one of mechanisms by which the carcinogen induces its carcinogenic action. Also, melatonin treatment strongly protects the studied organs against the toxic effect of 2-NP....

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Journal Article 2002; 23(4): 329-334 PubMed PMID: 12195236 Citation  Keywords:  Alkaloids:analysis, Animals, Bivalvia:chemistry, Chromatography, High Pressure Liquid, Ganglia, Invertebrate:chemistry, Isoquinolines:analysis, Mass Spectrometry,.   

UNLABELLED: Tetrahydropapaveroline and reticuline, isoquinoline alkaloids, were purified and identified in the pedal ganglia of the marine mollusk Mytilus edulis.

OBJECTIVES: To determine the presence of tetrahydropapaveroline and reticuline, isoquinoline alkaloids, in animal tissues previously shown to express opiate receptors.

METHODS AND RESULTS: This was achieved by high performance liquid chromatography coupled with electrochemical detection and finally identified by electro-spray ionization quadrupole time of flight mass spectrometry (Q-TOF). The expression of these two terahydroisoquinoline alkaloids in the animals neural tissue is at the level of 2.5+/-0.64 ng/ganglion and 1.8+/-0.52 ng/ganglion, respectively.

CONCLUSION: This finding suggests that morphine biosynthesis may occur in Mytilus neural tissues, and that the biosynthesis pathway may be similar to that reported in the poppy plant....

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Journal Article 2002; 23(4): 325-328 PubMed PMID: 12195235 Citation  Keywords:  Animals, Antineoplastic Agents:pharmacology, Astrocytes:cytology, Cerebral Cortex:cytology, DNA-Binding Proteins:metabolism, Gene Expression:drug effects, Glioma, Growth Inhibitors:pharmacology, Interferon-gamma:pharmacology, Interleukin-6:pharmacology, L.   

OBJECTIVES: The purpose of this study was to compare the effects of neurotrophic cytokines on the JAK/STAT transcription factors and the immediate early gene, c-fos, in C6 glioma cells and in primary astrocyte cultures.

METHODS: In this study we compared the effects of interleukin 6, leukemia inhibitory factor and interferon gamma on C6 glioma cells and on primary astrocyte cultures using electrophoretic mobility shift assay and quantitative solution hybridization/Northern Blot analysis.

RESULTS: We show that interleukin 6, leukemia inhibitory factor and interferon gamma treatment induce the nuclear STAT3 and STAT1 proteins to bind to the sis inducible element of c-fos in both C6 glioma cells and primary cortical astrocytes. Furthermore, quantitative solution hybridization and Northern blot analysis show the differential regulation of c-fos mRNA levels by interleukin-6 (8.1 and 4.0 folds) and leukemia inhibitory factor (5.4 and 3.2 folds) in C6 and astrocyte cultures (respectively). However, interferon gamma increases in c-fos mRNA levels (2.9 fold in both C6 and astrocyte cultures) were not significant in a one way ANOVA.

CONCLUSION: This study suggests that two initial cytokine signaling pathways are present and functional in C6 glioma cells and in primary astrocyte cultures....

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Journal Article 2002; 23(4): 321-324 PubMed PMID: 12195234 Citation  Keywords:  Adjuvants, Immunologic:pharmacology, Animals, Carcinogenicity Tests, Dehydroepiandrosterone:pharmacology, Estradiol:pharmacology, Female, Galanin:genetics, Gene Expression:drug effects, Pituitary Gland, Anterior:drug effects, Prolactin:blood, RNA, Messeng.   

OBJECTIVES: The effects of dehydroepiandrosterone (DHEA) on galanin (GAL) and prolactin (PRL) mRNA expression in the anterior pituitary of Fischer 344 rats were studied, taking in consideration that: (1) DHEA is an androgen with estrogenic activity on pituitary lactotrophs; (2) estrogens induce prolactinomas in Fischer 344 rats; and (3) GAL has been considered the main mediator of estrogen-induced lactotroph proliferation.

DESIGN: Female rats were ovariectomized and used as controls or treated during 2 weeks with DHEA (500 mg/kg/day or 5 mg/kg/day or 50 mg/kg/day) or estradiol (E2, 50 microg/kg/day), as a positive control for pituitary growth and GAL induction. GAL and PRL mRNA expression were studied by in situ hybridization.

RESULTS: Both DHEA and E2 induced PRL mRNA synthesis. However, DHEA neither produced pituitary enlargement nor GAL induction, in contrast to E2.

CONCLUSIONS: Our results shows that GAL is not involved in the estrogenic activity of DHEA on pituitary lactotrophs, and suggest that DHEA effects are exerted directly on the PRL gene or through another mechanism(s) not related to GAL....

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