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Journal Article 2001; 22(1): 53-73 PubMed PMID: 11393163 Citation  Keywords:  Adrenal Glands:physiology, Animals, Biological Clocks, Blood Pressure:physiology, Chronobiology Disorders:physiopathology, Chronobiology Phenomena, Chronotherapy, Circadian Rhythm:physiology, Drug Administration Schedule, Genomics, Homeostasis, Humans, Pi.   

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Journal Article 2001; 22(1): 53-73 PubMed PMID: 11393163 Citation  Keywords:  Adrenal Glands:physiology, Animals, Biological Clocks, Blood Pressure:physiology, Chronobiology Disorders:physiopathology, Chronobiology Phenomena, Chronotherapy, Circadian Rhythm:physiology, Drug Administration Schedule, Genomics, Homeostasis, Humans, Pi.   

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Journal Article 2008; 29(6): 1015-120 PubMed PMID: 19112418 Citation  Keywords:  Adaptation, Physiological, Adrenal Medulla:enzymology, Analysis of Variance, Animals, Catecholamines:biosynthesis, Dopamine beta-Hydroxylase:genetics, Gene Expression Regulation:physiology, Immobilization, Male, Phenylethanolamine N-Methyltransferase:gene.   

OBJECTIVE: Isolation of adult animals represents a form of psychsocial stress that produces sympatho-adrenomedullar activation. The aim of this work was to investigate the changes in gene expression and protein levels of catecholamine biosynthetic enzymes: tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in the adrenal medulla of naive control and chronically (12 weeks) socially isolated adult Wistar rat males and the response of these animals to additional immobilization stress (2 h).

METHODS: TH, DBH and PNMT mRNA levels were quantified by quantitative real-time RT-PCR (qRT-PCR). TH, DBH and PNMT immunoproteins were assayed by Western Blot.

RESULTS: In chronically isolated rats, gene expression levels of catecholamine biosynthetic enzymes in the adrenal medulla were decreased, but only TH mRNA was significantly decreased. However, protein levels of TH, DBH and PNMT of these animals were elevated by 55%, 20% and 18%, respectively, in relation to the corresponding control. Naive control and chronically socially isolated rats exposed to additional 2-h-immobilization showed increased gene expression of the examined enzymes, the increase being greater in socially isolated rats as compared to the controls. Additional immobilization of naive controls did not affect TH, DBH and PNMT protein levels. In contrast, this stress produced increased TH, DBH and PNMT protein levels in long-term socially isolated rats.

CONCLUSION: We can conclude that psychosocial stress expressed a differential influence on gene expression and protein levels of catecholamine biosynthetic enzymes in the adrenal medulla of adult rats. The results indicate a possible adaptation of catecholamine-synthesizing system at the level of TH gene expression in adrenal medulla of chronically isolated animals....

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Case Reports 2008; 29(6): 857-866 PubMed PMID: 19112416 Citation  Keywords:  Antineoplastic Combined Chemotherapy Protocols:therapeutic use, Biological Therapy:methods, Breast Neoplasms:therapy, Carcinoma, Ductal, Breast:therapy, Complementary Therapies, Female, Hormone Antagonists:administration & dosage, Humans, Middle Aged, Neo.   

: In this case presentation, a woman with breast carcinoma who chose to try Prof. L. DiBella's biological therapy (MDB), was found, after seven months, to have a 50% reduction in objective measures of her carcinoma and was totally cured after 14 months. The patient's recovery extended to bilateral axillary adenopathies, and took place without the toxicity normally associated with cancer treatment. MDB entails the use of anti-proliferative molecules such as somatostatine, prolactin, and estrogen inhibitors, along with differentiating and apoptotic molecules such as melatonin, retinoids, vitamins C, D3, and E, calcium, and amino-sugars, combined with minimal doses of chemotherapy. The hemato-chemical exams showed no damage, with a progressive reduction of prolactin, estradiol, IGF1, and maintenance of low levels of GH. The achievement of objective results, without toxicity, in this case, proves the effectiveness of this therapy and confirms the positive results already published on the use of MDB for Low-Grade NHL, and pulmonary carcinomas in the 3rd and 4th stages. MDB, without the need for either hospitalization or day hospitalization, without toxicity, and without even minimally reducing the patient's daily work routine, allowed the patient to avoid surgical trauma and the significant collateral effects of chemo- and radiotherapy. Timely use of MDB as the first line therapy, in a patient which had not been debilitated by the mutagenic, toxic, and immuno-depressive effects of chemo- and radiotherapy, contributed greatly to the final outcome. We feel it is useful to highlight this case in an effort to stimulate interest and further study into the oncological potential of MDB biological and receptor therapy....

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Case Reports 2008; 29(6): 867-870 PubMed PMID: 19112415 Citation  Keywords:  Adult, Brain Neoplasms:complications, Central Nervous System Neoplasms:complications, Humans, Lymphoma, B-Cell:complications, Magnetic Resonance Imaging, Male, Multiple Sclerosis, Relapsing-Remitting:complications,.   

: We present the patient with the diagnosis of multiple sclerosis (MS), relapsing-remitting form with long lasting remission. Unexpectedly, this patient presented dramatical clinical deterioration and revealed clinical symptoms such as bradypsychia, cognitive symptoms, central vestibulare syndrome, spastic quadruparesis. Clinical findings suggested secondary progressive MS, but MRI called in question this diagnosis. The MRI appearance suggested, that MS had been complicated by a different brain pathological lesion, and the brain biopsy was indicated. A histological examination confirmed primary CNS lymphoma (PCNSL). This case exemplifies important aspects of clinical neurology. A re-evaluation of the diagnosis of MS should always be performed in a patient when new symptoms are presented that are unusual or could be due to other pathological processes. MRI offers the highly sensitive way to detect the coexistence of MS and other brain disease. Primary goal of imaging modalities is differential diagnosis between demyelinating diseases, such as MS and other brain lesions. Advanced focus demand contrast- enhancing and mass- effect lesions. It is important to realize, that contrast-enhancement and brain edema may be mitigated by treatment with corticosteroids. In some cases a brain biopsy is needed....

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Journal Article 2008; 29(6): 958-964 PubMed PMID: 19112413 Citation  Keywords:  Analysis of Variance, Animals, Estrous Cycle:metabolism, Female, Follicle Stimulating Hormone, beta Subunit:analysis, Follistatin:analysis, Gene Expression Regulation:physiology, Gonadotropin-Releasing Hormone:antagonists & inhibitors, Hormone Antagonists.   

OBJECTIVES: Neural control of the anterior pituitary function consists of the interplay of neuropeptides action, gonadal steroid hormones and many other factors. The physiological effect of this regulatory action is the release and synthesis of protein hormones in the precise time and quantity. The main factor responsible for the gonadotropins release and synthesis is the gonadotropin-releasing hormone (GnRH). We must still study the modulation of the synthesis of the gonadotropins subunits - LHbeta, FSHbeta and alpha subunit by different forms of GnRH and by its analogs, in order to better understand the regulation of gonadotropin release and synthesis. THE AIM of this study was to develop real-time PCR assays of five candidate reference genes for normalization purposes in order to quantify target transcripts in anterior pituitary cells during the preovulatory period. Moreover, we focused on the influence of GnRH receptor antagonist (antide) treatment on mRNA expression levels of GPalpha, LHbeta, FSHbeta, FST(follistatin) and PRL(prolactin) genes in these cells.

MATERIAL AND METHODS: Anterior pituitary cells were obtained from pituitary glands of four mature pigs at the preovulatory phase. Cells were incubated with or without antide and relative mRNA level of target genes was measured using the Applied Biosystems 7500 Real Time System. For an exact comparison of mRNA quantity, the stability of five reference genes, ACTB, B2M, GAPDH, RPL1, and TOP2B was evaluated to choose the most appropriate reference gene for qRT-PCR normalization in the pituitary cells. Expression stability of reference genes was calculated using the geNorm application. The developed method of PCR assay was applied to study gene expression in pig pituitary cells in short culture.

RESULTS: The most stably expressed genes in the pituitary cells were GAPDH and TOP2B. The expression of ACTB, B2M and RPL1 appeared to be highly unstable. After normalization to the GAPDH/TOP2B, results showed that the mRNA expression of the FSHbeta gene was highest in comparison with LHbeta, GPalpha, FST and PRL genes (p<0.005). Pre-treatment of cells by the antide resulted in lower mRNA expression of these genes, while FSHbeta mRNA had a significantly lower expression (p<0.05) in comparison with control.

CONCLUSIONS: Real-time PCR analysis of the expression of LHbeta, FSHbeta, alpha subunit, follistatin and prolactin genes in porcine anterior pituitary cells during the preovulatory period is suitable for the study of modulatory action of metal complexes with GnRH on the expression of these genes....

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Comparative Study 2008; 29(6): 917-923 PubMed PMID: 19112412 Citation  Keywords:  Animals, Behavior, Animal:drug effects, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Interactions, Exploratory Behavior:drug effects, Male, Motor Activity:drug effects, Neuropeptides:administration & dosage, Neuroprotective Agents:.   

OBJECTIVES: On the animal model of trimethyltin (TMT) induced behavioral deficits the effect of chronic treatment with spirocyclic dipeptide cyclo/alanyl-l-amino-l-cyclopentane-carbonyl (alaptide, AL) was evaluated in adult male rats.

METHODS: Changes in the spontaneous behavioral repertoire were investigated in the open-field test on Day 21 (Session 1) and Day 28 (Session 2) after a single oral TMT administration.

RESULTS: In Experiment 1, rats given the highest TMT dose (7.5 mg/kg) exhibited significantly increased total number of behavioral patterns, the floor sniffing being the most frequent pattern. While the medium TMT dose (5 mg/kg) had a similar effect only in Session 1, the lowest TMT dose (2.5 mg/kg) was entirely ineffective. In Experiment 2, an explicit beneficial influence of both AL doses (5 and 10 mg/kg) given for 10 days before and 10 days after TMT (7.5 mg/kg) on the spontaneous behavior repertoire was observed in both Session 1 and Session 2. The total number of patterns and the time spent in individual patterns of AL+TMT treated animals did not differ from the controls and those given AL alone.

CONCLUSION: We conclude that sufficiently long AL treatment interfered with deleterious effects of TMT and forestalled changes in the structure and timing of spontaneous behavioral patterns. Thus, AL can be designated as a substance having "neuroprotective" effects....

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Comparative Study 2008; 29(6): 990-994 PubMed PMID: 19112411 Citation  Keywords:  Adult, Antipsychotic Agents:administration & dosage, Chi-Square Distribution, Early Diagnosis, Female, Humans, Longitudinal Studies, Male, Middle Aged, Outcome Assessment (Health Care), Prognosis, Psychotic Disorders:complications, Retrospective Studies, .   

OBJECTIVES: A long duration of untreated psychosis (DUP) is known to be associated with a poorer prognosis and with worse symptomatic and functional outcome. The aim of the study was to test the hypothesis that early detection and treatment with antipsychotics in the prodromal phase of the illness improves the outcome; to compare short and long-term outcome in patients with DUP longer than 1 year (group 1) with patients that were treated already in the prodromal phase of the disease (group 0).

DESIGN AND SETTING: Eighty-seven patients with schizophrenia were included to the retrospective study, 37 patients to group 0 and 50 patients to group 1. The course and outcome of the disease was studied in the two groups. The severity of schizophrenia was evaluated by measuring several outcome parameters. The symptom severity was evaluated using a check list developed from CAARMS inventory; the average daily dose of antipsychotics was calculated as well as the number and duration of hospital admissions. Groups were compared during the acute psychosis of first episode (t1) and at the conclusion of the study (t2).

RESULTS: More symptoms of greater intensity were present during the first and second evaluations in group 1 as compared to group 0 patients. The patients in group 0 needed lower dosages of antipsychotics even several years after treatment had been initiated. This effect persisted until the final evaluation; 11% were without antipsychotics at the conclusion of the study. Patients in group 1 were hospitalized more frequently; they needed more hospitalizations and these were of longer duration. Only 38% of patients in group 0 were treated in the hospital, 27% were hospitalized only once.

CONCLUSIONS: Better outcome can be achieved with early antipsychotic treatment. Patients with long DUP differ from patients who were treated already in the prodromal phase in several outcome measures....

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