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Case Reports 2005; 26(3): 213-218 PubMed PMID: 15990724 Citation  Keywords:  Adolescent, Adult, Basal Ganglia:pathology, Calcinosis:genetics, Child, Child, Preschool, Czech Republic, Diagnosis, Differential, Dyskinesias:genetics, Family Health, Female, Humans, Magnetic Resonance Imaging, Male, Mutation, Pantothenate Kinase-Associa.   

: Hallervorden-Spatz disease (HSD) was and is known as a rare disorder primarily characterized by progressive extrapyramidal dysfunction and dementia alongside optic nerve atrophy or retinal degeneration and pyramidal signs. The rate of occurence of HSD is thus far unknown. Progress in DNA diagnostics stirred up a nomenclature and from HSD, or, perhaps better put, the Hallervorden-Spatz syndrome, crystallized the pantothenate kinase-associated neurodegeneration (PKAN) as a clearly defined entity on the level of DNA. In this paper, we present our first results and experience in the diagnosis of PKAN in the Czech Republic and discuss questions related to differential diagnosis....

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Journal Article 2005; 26(3): 209-212 PubMed PMID: 15990723 Citation  Keywords:  Acromegaly:genetics, Adenoma:genetics, Adult, Aged, Biomarkers, Tumor:genetics, Female, Gene Expression Regulation, Neoplastic, HeLa Cells, Humans, Inhibitor of Apoptosis Proteins, Male, Microtubule-Associated Proteins:genetics, Middle Aged, Neoplasm Prot.   

UNLABELLED: Survivin has received great attention due to its expression in many human tumours and its potential as a therapeutic target in cancer. Its expression is developmentally regulated: present during fetal development, it is undetectable in terminally differentiated normal adult tissue. Survivin expression has been described to be cell cycle-dependent and restricted to the G2-M checkpoint, where it inhibits apoptosis in proliferating cells.

OBJECTIVES: The aim of our study was to determine the survivin expression in different types of pituitary adenomas.

METHODS: Tissue samples were obtained during surgical removal of the tumour from 12 patients with diagnosed: acromegaly in seven cases, non-functioning pituitary tumours in four cases and prolactinoma in one case. Six patients with acromegaly received long-acting somatostatin analogues before tumour resection. After RNA extraction and cDNA synthesis, the amplification of specific survivin's gene fragment was performed.

RESULTS: In agreement with the current view that survivin is a tumor-associated antigen, highly expressed in various tumours, we found the presence of survivin expression as a characteristic feature of human pituitary adenomas. The findings of our study demonstrated the presence of an active survivin gene in all twelve analysed pituitary tumours.

CONCLUSIONS: Based on these findings, we conclude that the estimation of survivin expression in human pituitary tumours may help predict tumour growth and prognosis....

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Journal Article 2005; 26(3): 197-203 PubMed PMID: 15990721 Citation  Keywords:  Aging:physiology, Animals, Antibodies, Blood Pressure:physiology, Body Temperature:physiology, Caloric Restriction, Cell Survival:physiology, Estrogen Receptor alpha:immunology, Female, Immunohistochemistry, Luteinizing Hormone:metabolism, Mice, Mice, Inb.   

: Life-long calorie restriction (CR) remains the most robust and reliable means of extending life span in mammals. Among the several theories to explain CR actions, one variant of the neuroendocrine theories of aging postulates that changing hypothalamic sensitivity to endocrine feedback is the clock that times phenotypic change over the life span. If the feedback sensitivity hypothesis is correct, CR animals should display a significantly different pattern of hormone-sensitive cell density and distribution in the hypothalamus. Of the many endocrine signal receptors that may be involved in maintaining hypothalamic feedback sensitivity, our study has selected to begin mapping those for estrogen (E). Altered hypothalamic sensitivity to E is known to schedule reproductive maturation and influence reproductive senescence. Taking estrogen receptor-alpha (ERalpha) immunoreactivity as an index of sensitivity to E, we counted ERalpha immunoreactive and non-immunoreactive cells in the pre-optic hypothalamus of young (6 weeks), ad-libitum (Old-AL) fed old (22 months), and calorie restricted (Old-CR) old (22 months) female B6D2F1 mice. An automated imaging microscopy system (AIMS) was used to generate cell counts for each sampled section of pre-optic hypothalamus. Results show a 38% reduction in ERalpha immunoreactive cells and an 18% reduction in total cell numbers in AL-old mice in comparison to young mice. However, CR mice only show a 19% reduction in ERalpha immunoreactive cells and a 13% reduction in total cell numbers in comparison to young mice. This indicates CR prevents age-related cell loss and maintains estrogen sensitivity in the pre-optic hypothalamus of old female B6D2F1 mice....

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Editorial 2005; 26(3): 167-171 PubMed PMID: 15990717 Citation  Keywords:  Data Interpretation, Statistical, Neuroendocrinology, Statistics as Topic:methods,.   

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Comparative Study 2005; 26(2): 152-159 PubMed PMID: 15855888 Citation  Keywords:  Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Pituitary Neoplasms:mortality, Prolactinoma:mortality, Retrospective Studies, Sex Characteristics, Treatment Outcome,.   

BACKGROUND/AIMS: Prolactinomas are the most common tumors of the pituitary gland. Only few studies have documented gender-related differences in the growth and presentation of these tumors, but nothing is known about their effects on their subsequent surgical outcome and prognosis.

PATIENTS & METHODS: Twenty-six patients with prolactinomas, that met strict immunohistochemical and electron microscopic criteria and were surgically treated between January 1990 and June 1997, were retrospectively reviewed. The patient charts, as well as histological (mitotic index) immunohistological (MIB-1 labeling-index) and electronic microscopical staining were analyzed.

RESULTS: Nineteen patients were women, and seven were men; the female-to-male-ratio was 2.7:1. Men were significantly older, both at diagnosis and surgery. Menstrual abnormalities were the most common presenting symptom in women, whereas impotence predominated in men. Psychological symptoms were significantly more common in men than in women. Men had a significantly shorter preoperative duration of symptoms and higher preoperative serum prolactin levels than women. The preoperative prolactin levels and proliferative activities (mitotic index, MIB-1 labeling index) were lower in women compared to men and showed a direct correlation to postoperative outcome. The overall outcome was significantly better in women than in men. In women, age less than 35 years was a beneficial prognostic factor, and preoperative bromocriptine treatment was associated with a significantly worse long-term-outcome.

CONCLUSION: The biology and the clinical course of prolactinomas seem to differ in women and men. In men, the preoperative durations of symptoms is shorter, the tumors are larger and more invasive at surgery, and the outcome is worse than in women. Based on proliferative activities (mitotic index, MIB-1 labeling index), the predominance of marcoadenomas in men is due to a high frequency of rapidly growing tumors, which are often invasive and frequently correlated with a worse outcome. Our findings may justify a more aggressive therapeutic approach to prolactinomas in men than in women....

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Clinical Trial 2005; 26(2): 131-135 PubMed PMID: 15855884 Citation  Keywords:  Adolescent, Adult, Autoantibodies:analysis, Drug Combinations, Estradiol:therapeutic use, Estriol:therapeutic use, Female, Germ Cells:immunology, Hormone Replacement Therapy, Humans, Medroxyprogesterone Acetate:therapeutic use, Menstruation Disturbances:c.   

INTRODUCTION: To investigate levels of antiovarian autoantibodies in girls and young women with disturbances of menstrual cycle before and during treatment with hormonal therapy. To explain morphological changes in ovarian structure in these patients.

MATERIAL AND METHODS: Studied group included 39 patients. 18 patients were treated for primary amenorrhoea, 21 for menstrual cycle disorders. Patients included in the study were repeatedly examined at the beginning of the study and after six months during which they were treated by estrogen and gestagen. In all patients we have tested FSH, LH and FSH/LH ratio, presence of antiovarian antibodies. Results were compared with those obtained in control women. 21 antiovarian antibodies positive patients were indicated for laparoscopic biopsy. Bioptic sample was examined using light and electron microscopy.

RESULTS: Our treatment with hormonal therapy lead to the reduction of ovarian antigens. In 85% of the cases marked decrease of antiovarian autoantibodies levels was observed, while in 28% of the cases the levels were undetectable. From morphological changes of the bioptic sample enhanced atresia of follicules at different developmental stages was frequently observed. It evoked marked reduction of follicular apparatus up to its complete disappearing.

CONCLUSION: The results of our study and mapping of the antiovarian antibodies positivity support our hypothesis that the antiovarian antibodies positivity corresponds with the clinical symptoms. Appropriate treatment with hormonal replacement therapy minimizes ovarian destruction, preserves ovarian hormonal functions and saves healthy ovarian tissue necessary for future fertility....

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Comparative Study 2005; 26(2): 125-130 PubMed PMID: 15855883 Citation  Keywords:  Action Potentials:physiology, Animals, DNA-Binding Proteins:metabolism, Electrophysiology, Hypothalamus:cytology, In Vitro Techniques, Male, Milk Proteins:metabolism, Neurons:metabolism, Prolactin:physiology, Rats, Rats, Wistar, Receptors, Prolactin:metab.   

OBJECTIVES: The study investigated the role of prolactin (PRL) in modulating STAT5 and electrical activity of magnocellular neurones in the supraoptic (SO) nucleus of male rats.

METHODS: Evidence of expression of STAT5 in the SO nucleus was investigated by immunocytochemical methods. Effect of blocking prolactin receptors on STAT 5 expression was investigated by Western blotting following transfection of SO neurones with a dominant negative mutant form of the PRL receptor. Prolactin-induced changes in electrical activity were investigated by extracellular recording in hypothalamic slices.

RESULTS: A high proportion of SO neurones in male rats expressed immunoreactive STAT5. Levels of activated STAT5 within the SO nucleus of PRL-treated rats was reduced following transfection with a dominant negative mutant form of the PRL receptor, as compared to rats transfected with wild type PRL receptor. Electrophysiological recordings from the SO nucleus in horizontal brain slices showed that approximately 25% of neurones were responsive to PRL, with both inhibitory and excitatory effects being observed. Cells displaying PRL responses included pharmacologically-identified oxytocinergic neurones.

CONCLUSIONS: Collectively, the results suggest that central PRL targets neurones of the SO nucleus, influencing both activation of the JAK-STAT signalling pathway and neuronal excitability. Whilst the functional significance of this interaction remains to be established, it might be important in co-ordinating oxytocin secretion with physiological events associated with changes in plasma PRL, or in mediating a feedback loop in the oxytocinergic regulation of lactotrophs....

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Comparative Study 2005; 26(2): 121-124 PubMed PMID: 15855882 Citation  Keywords:  Animals, Exploratory Behavior:drug effects, Female, Habituation, Psychophysiologic:drug effects, Male, Motor Activity:drug effects, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Sex Factors, Testosterone:pharmacology, Vocalization, Animal:drug effec.   

OBJECTIVES: The purpose of the present study was to characterize the influence of testosterone administered to pregnant females on offsprings postnatal behavioral strategies in the open field.

METHODS: The influence of maternal testosterone on behaviour of 23 day old male and female offsprings was studied in a 20-minute open field test. A total of 9 behavioural events were compared between a control (male n=12, female n=8) and a testosterone group (male n=9, female n=9). Dynamics and patterns of association of these behavioural events were analyzed. The testosterone group was prenatally exposed to testosterone (a single intramuscular injection of 2.5 mg testosteroni isobutyras on gestation day 14).

RESULTS: Male offsprings exposed prenatally to testosterone displayed significantly high levels of ambulation (P<0.05), sniffing (P<0.01), sniffing the air (P<0.05), urination (P<0.05) and significantly lower level of vocalization (P<0.05) than control. Female offsprings exposed prenatally to testosterone displayed significantly higher level of sniffing the air (P<0.05) than control. Significant differences in the dynamics of habituation process were registered only in the group of male. They were from 5 to 10 min in ambulation (P<0.05), from 10 to 15 min in sniffing (P<0.05) and vocalization (P<0.05), from 10 to 15 min and from 15 to 20 min in sniffing the air (P<0.05) and from 0 to 5 min in defecation (P<0.05) and urination (P<0.01).

CONCLUSION: Our results suggest that maternal testosterone may influence especially male postnatal open field strategies....

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