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Journal Article 2012; 33(3): 301-303 PubMed PMID: 22635089 Citation  Keywords:  Adult, Age of Onset, Brain Injuries:complications, Disease Progression, Growth Disorders:etiology, Human Growth Hormone:deficiency, Humans, Male, Polyendocrinopathies, Autoimmune:complications,.   

: Both adult-onset growth hormone deficiency and autoimmune polyglandular syndrome are more frequent clinical entities than previously thought. In light of research carried out in recent years, it seems that growth hormone deficiency may be associated with proinflammatory state. This study describes a unique case of adult-onset growth hormone deficiency secondary to a traumatic brain injury in a young man, which was followed by the development of autoimmune polyglandular syndrome type 3. We discuss diagnostic and treatment dilemmas associated with discovering and management of both disorders in this patient. We conclude that in predisposed individuals growth hormone deficiency may lead to the development of autoimmune disorders of endocrine glands and/or exacerbate their clinical course....

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Case Reports 2012; 33(3): 298-300 PubMed PMID: 22635088 Citation  Keywords:  Aminoquinolines:administration & dosage, Disease Progression, Dopamine Agonists:administration & dosage, Female, Humans, Hyperprolactinemia:complications, Prolactin:blood, Thyroiditis, Autoimmune:complications, Young Adult, Zona Glomerulosa:immunology,.   

: Prolactin is a hormone with a multidirectional proinflammatory action. It has an anti-apoptotic effect, enhances proliferative response to antigens and mitogens, as well as enhances the production of immunoglobulins and autoantibodies. Increased prolactin levels are commonly observed in various organ and multi-organ specific autoimmune diseases. In our article, we report a case of a woman who developed progression of autoimmune thyroid disorder and developed insufficiency of the zona glomerulosa when her prolactin levels were increased. A normalization of plasma prolactin levels by quinagolide and replacement of risperidone with aripiprazole improved her clinical condition. Our study suggests that, in some patients, hyperprolactinemia may predispose to the development and progression of autoimmune disorders of endocrine glands....

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Case Reports 2012; 33(3): 257-259 PubMed PMID: 22635079 Citation  Keywords:  Androgens:metabolism, Female, Humans, Immunohistochemistry, Middle Aged, Ovarian Neoplasms:complications, Ovary:pathology, Sertoli-Leydig Cell Tumor:complications, Testosterone:metabolism, Virilism:etiology,.   

: Sertoli-Leydig cell tumor is a rare and usually unilateral tumor of the ovary occurring in women's reproductive age. Only about 10% of these patients are over 50 years of age. One third of these patients are suffering from signs of virilisation. This work summarizes the morphological and immunohistochemical characteristics of this tumor in a 56-year old woman with clinical signs of virilisation....

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Journal Article 2012; 33(2): 138-148 PubMed PMID: 22592194 Citation  Keywords:  Animals, Body Weight:drug effects, Estradiol:blood, Female, Follicle Stimulating Hormone:blood, Gonadotrophs:drug effects, Gonadotropin-Releasing Hormone:blood, Growth Hormone:blood, Hypothalamus:drug effects, Insulin-Like Growth Factor I:metabolism, Lept.   

OBJECTIVE: Available data suggest that estrogens and leptin play a role in the control of the pubertal process. In humans and some mammal species the increase of the activity of gonadotropic axis accompanies the decrease in the rate of growth at puberty. The effect of 17β-estradiol and/or leptin administration on the somatotropic and gonadotropic axes was studied using prepubertal female rats as an animal model.

MATERIAL AND METHODS: Prepubertal female rats received estradiol/saline, estradiol/leptin, oil/leptin or oil/saline (vehicles) respectively. The changes of growth rate, and serum 17β-estradiol, leptin, GH, IGF-I and gonadotropins levels as well as LHRH and estrogen receptor (ER) concentrations in the medial basal hypothalamus (MBH) and the pituitary were determined. All hormones concentrations were measured by radioimmunoassay and ER by radioligand methods .

RESULTS: In estradiol and/or leptin treated animals noticeable reduction of rate of growth was found. The decrease of growth in response to estradiol treatment accompanied the increase GH level and the decrease of IGF-I concentration in the circulation. Both hormones operating together activated reproductive axis, what was manifested by a significant increase of LHRH abundant in the hypothalamus as well as elevated LH and FSH levels in the circulation. In these rats a significant decrease of the estrogen receptor concentrations in the pituitary was observed.

CONCLUSION: The role of estradiol and leptin in the control of growth and reproduction seems to overlap only partially. Estradiol plays a significant role in the activation of the reproductive axis, and leptin takes part as a permissive factor in pubertal process....

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Journal Article 2012; 33(1): 90-97 PubMed PMID: 22467118 Citation  Keywords:  Double-Blind Method, Humans, Memory, Short-Term, Prefrontal Cortex, Schizophrenia:diagnosis, Transcranial Magnetic Stimulation,.   

OBJECTIVE: The objective of the study was to find out whether, under the conditions of a double-blind, placebo coil controlled study, high-frequency repetitive transcranial magnetic stimulation (TMS) over the left prefrontal cortex will show positive effects on working memory with simultaneous assessment of respective changes in neuronal activation.

RESULTS: Stimulation treatment led to a reduction of seriousness of negative schizophrenia symptoms in both comparative groups. However, mutual comparison of real (n=19) and sham (n=11) rTMS, respectively, has shown that the effect of real rTMS was statistically significantly higher compared with placebo stimulation. During stimulation treatment an improvement in working memory performance was also found. No statistically significant difference between the real and placebo sham rTMS, respectively, was established. The rate of neuronal activation did not change at all during rTMS treatment.

CONCLUSIONS: From clinical point of view rTMS seems to be a well-tolerated neurostimulation method for treatment of negative schizophrenia symptoms with favourable of impact on cognitive functions....

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Journal Article 2012; 33(1): 76-80 PubMed PMID: 22467116 Citation  Keywords:  Abortion, Habitual:epidemiology, Factor V, Female, Heterozygote, Humans, Methylenetetrahydrofolate Reductase (NADPH2):genetics, Mutation, Pregnancy, Prothrombin, Thrombophilia,.   

OBJECTIVE: The aim of the study was to evaluate the importance of screening for thrombophilic mutations after the first early pregnancy loss.

SETTING: Thrombophilic mutations were examined in a sample of 100 women with at least one miscarriage. DNA was isolated from venous blood sample. We used methods of microarray, fragmentation analysis, High Resolution Melting and PCR-ARMS with following gel electrophoresis and visualisation. Chi-square test and in cases of low expected frequencies Yates correction were used to compare relative frequencies of individual mutations. The comparison of averages was performed by t-test.

RESULTS: We detected prevalence of factor V and II mutation of 9% and 3%, respectively. Single MTHFR mutation was found in 59% and double heterozygous MTHFR mutation in 23% of cases. No mutation was present in only 6% of the study group. Heterozygous mutations of factor V occurred 1.8 times more frequently in our study group compared to the general Czech women population. Also, the frequency of factor II mutation was 1.5-3 times higher. No carrier of these mutations had overt coagulation disorder, history of thromboembolic disease or that of habitual abortions.

CONCLUSIONS: The frequency of thrombophilic mutations in the group of women with early pregnancy loss is 1.5-3 times higher than in the general population....

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Journal Article 2012; 33(1): 67-75 PubMed PMID: 22467115 Citation  Keywords:  Anisotropy, Diffusion Tensor Imaging, Humans, Multiple Sclerosis, Physical Therapy Modalities, Pilot Projects,.   

OBJECTIVES: The aim of this study was to confirm the immunoregulatory and anti-inflammatory changes in the immunologic profile after two months of the facilitation physiotherapy in patients with multiple sclerosis; and to determine whether the changes in the immunologic profile correlate with the changes in dehydroepiandrosterone, the brain microstructure and clinical functions.

DESIGN & SETTING: A group of 12 patients with multiple sclerosis was examined twice: at the beginning and 2 months later after the patients had undergone the facilitation therapy. Standardized tests evaluating chosen clinical functions (balance, righting, equilibrium and protective reactions, tremor, dysdiadochokinesis, dysmetry, fine hand function and walking), immune parameters (parameters of the humoral and cellular immunity), dehydroepiandrosterone and diffusion tensor imaging (the fractional anisotropy, mean diffusivity) were measured. The patients underwent the facilitation physiotherapy in two sessions lasting two hours each week for two months.

RESULTS: All clinical and diffusion tensor imaging parameters significantly improved following the therapy. Without the correction for multiple comparisons, there were significant changes in the IgG, IgG1 subclasses, in the numbers of Neutrophils and Lymphocytes, the T cells (CD3+) absolute number, the T cytotoxic subpopulation (CD3+CD8+) absolute number, B cells (CD19+) and the Natural killer cells. In addition, there was a significant correlation between the changes in the clinical functions and the changes in IgG1 (r=0.67), and between the changes in the mean diffusivity and the changes in CD3+CD8+ absolute (r=-0.61). The changes in the immune parameters and the mentioned correlations were not significant in view of the number of comparisons and thus necessitate further validation. No changes in the dehydroepiandrosterone concentration after the therapy were confirmed.

CONCLUSION: The study suggests new possibilities of physiotherapy to influence the psycho-neuro-endocrine-immune response in patients with multiple sclerosis....

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Journal Article 2012; 33(1): 26-33 PubMed PMID: 22467108 Citation  Keywords:  Adenomatous Polyposis Coli, Animals, Disease Models, Animal, Genes, APC, Germ-Line Mutation, Mice, Mutation, Phenotype,.   

OBJECTIVES: Familial adenomatous polyposis (FAP) is an autosomal dominant disease characterized by the presence of hundreds to thousands of benign polyps in the colon. If not removed prophylactically they represent a risk of developing malignant cancer with an almost 100% penentrance. FAP is induced by germline mutation in the APC gene. Tumorigenesis launched a second somatic mutation of APC gene allele, leading to synthesis of non-functional APC protein. One of the possibilities of cancer prevention could be an alternative gene therapy using bacteria as vectors for delivery of therapeutic protein molecules.

MATERIAL AND METHODS: For this purpose mice model APC+/APC1638N with mutation in one allele murine homolog of the APC gene were used. Mice were fed orally commercial nutrition enriched with 0.5 ml PBS buffer with 5% milk containing 5×108 recombinant bacterial cells DE3plys6 bearing plasmid with cloned APC gene twice a week during 42 weeks. Afterwords mice were killed by thiopental, gastrointestinal tracts were removed, microscopically, macroscopically inspected for polyps/neoplastic lesions and immunohistochemically investigated with polyclonal rabbit antibody against APC protein.

RESULTS: We have cloned full-lenght APC gene into vector for expression in bacterial cells Escherichia coli BL21(DE3) and BL21(DE3) pLysS. Expression of the APC protein, induced by IPTG, was detected in protein extracts of three bacterial clones: DE3104-11, DE3pLys5, DE3pLys6. APC protein was identified by Western blot analysis using monoclonal and polyclonal antibodies against the APC protein. Bacteria of clone DE3pLys6 were orally administered to APC+/APC1638N mice with mutations in the APC gene. All transgenic mice without therapy developed adenomatous polyps in the gastrointestinal tract. Transgenic mice treated by oral administration of bacteria expressing functional APC protein developed polyps in 33.3%. The remaining four mice 66.7% were without polyps development.

CONCLUSION: Administration of APC gene expressing by bacteria to transgenic mice with mutation in APC gene leads to reduction in the number of mice developing polyps in the gastrointestinal tract. The effect of bacterially expressed APC protein in elimination of intestinal polyps or tumors has been monitored. These are our preliminary results and for possible confirmation of our hypotheses still more research is needed....

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