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Journal Article 2010; 31(2): 187-192 PubMed PMID: 20424582 Citation  Keywords:  Adult, Age of Onset, Czech Republic, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Male, Middle Aged, Mutation, Parkinson Disease:genetics, Phenotype, Polymerase Chain Reaction, Polymorphism, Genetic, Ubiquitin-Protein Ligases:genetics,.   

OBJECTIVES: Mutations in several genes such as parkin can be detected in up to 20% of patients with early-onset Parkinson's disease (EOPD). The aim of our study was to determine the frequency of parkin alterations and phenotypic characteristics in Czech EOPD patients.

METHODS: A total of 45 EOPD individuals (age at onset <45 years) were phenotyped and screened for parkin mutations.

RESULTS: In total, 19 patients (42.2%) were carriers of previously described heterozygous genetic alterations. Parkin mutations (Ex2del, R402C) were identified in two (4.4%) cases, non-pathogenic variant A82E plus polymorphism D394N occurred in one (2.2%) patient and parkin polymorphisms (3x S167N, 1x R334C, 7x V380L, 4x D394N) were found in 15 (34.9%) individuals. Furthermore, the G2019S mutation in the LRRK2 gene was found in one (2.2%) subject.

CONCLUSION: The clinical characteristics of our patients correspond to previous descriptions of EOPD phenotype. This is the first report on EOPD-associated genetic alterations among Czech patients. Our results support the hypothesis that single heterozygous parkin variants may act as risk factors for EOPD....

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Journal Article 2010; 31(2): 265-269 PubMed PMID: 20424578 Citation  Keywords:  Acromegaly:complications, Adult, Arthralgia:drug therapy, Cognition:drug effects, Female, Follow-Up Studies, Growth Hormone:antagonists & inhibitors, Headache:drug therapy, Humans, Interpersonal Relations, Male, Middle Aged, Motor Activity:drug effects, O.   

OBJECTIVES: Acromegaly is a chronic disease caused by excessive growth hormone secretion resulting in bone and soft tissue overgrowth. Body image changes as well as systemic complications may considerably influence patients' psychological health and disturb everyday activities. The aim of this study was to determine the effect of octreotide treatment on somatic and psychological symptoms of acromegaly, and thus on patients' quality of life.

MATERIALS AND METHODS: The study was conducted on 15 patients with acromegaly. The average duration of octreotide therapy was 5.6 years (1-10 years). The respondents created a list of subjective signs and symptoms of acromegaly before treatment and reported changes observed during therapy. The psychological examination was performed with appropriate test scales assessed patients' self-efficacy, emotional control, psychological gender and their life satisfaction.

RESULTS: The most important changes observed during octreotide therapy were associated with head and joint pain relief and reduction of physical limitations. The patients also noticed the improvement of cognitive functions and interpersonal relations. The study revealed average life satisfaction in the group. The patients on the one hand demonstrated high self-efficacy and on the other hand - intensive repression of emotions. The undifferentiated sex-role schema dominated in group.

CONCLUSIONS: The study proved a significance of octreotide therapy in acromegalic patients' life. In spite of chronic disease, all the respondents reported good quality of life (average life satisfaction). Additionally, their high self-efficacy helps to cope with the disease. Nevertheless, undifferentiated sex role schema in the study group suggests lack of behavioral flexibility and high emotional repression predicts negative somatic consequences....

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Journal Article 2010; 31(2): 256-260 PubMed PMID: 20424577 Citation  Keywords:  Acromegaly:blood, Adult, Cathepsin B:blood, Cysteine Proteinase Inhibitors:blood, Female, Human Growth Hormone:blood, Humans, Insulin-Like Growth Factor I:metabolism, Male, Middle Aged,.   

OBJECTIVE: Acromegaly is a rare disease due to growth hormone (GH) excess. Patients must be carefully follow up because of mortality and co-morbidity increased risks. Since routinely used GH and insulin-like growth factor-1(IGF-1) estimations are not always sufficient, patients require assessment of organ- or tissue-specific tests. Cysteine proteases (CP), including cathepsin B, have been tested in a number of pathologies in respect of a role in pathogenesis and potential utility in the disease activity and prognosis assessment. There is lack of data on CP activity in acromegaly.

MATERIALS AND METHODS: In present study cathepsin B-like and cysteine peptidase inhibitor (CPI) activities have been tested in 29 acromegaly patients and in 15 healthy controls. Cathepsin B activity was assayed with N-bansoyl-DL-arginine-beta-naphthylamide (BANA) as substrate by the Barrett method. CPI activity was determined by measuring the inhibition of papain.

RESULTS: Serum cathepsin B activity (median: 1.38 U/ml) and CPI activity (median: 93.08 U/ml) were higher in acromegaly then in controls (0.93 U/ml and 82.55 U/ml, p=0.000017 and 0.00285, respectively). Neither cathepsin B nor CPI activity was correlated with GH or IGF-1 level. No correlation was recorded between cathepsin B and CPI activity.

CONCLUSION: It was shown for the first time that cathepsin B and CPI activities are increased in acromegaly. These findings suggest to study cathepsin system as an adjuvant parameter in the assessment of the overall acromegaly complications. Moreover, CP may be involved in pathomechanism of organ complications in acromegaly and may interfere with IGF-1 action....

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Journal Article 2010; 31(2): 261-264 PubMed PMID: 20424576 Citation  Keywords:  Adult, Aged, Catalase:blood, Diabetes Mellitus, Type 2:blood, Diabetic Neuropathies:blood, Endothelin-1:blood, Endothelium:physiopathology, Female, Glutathione:blood, Humans, Male, Middle Aged, Neuralgia:blood, Nitric Oxide:blood, Oxidative Stress, Survey.   

OBJECTIVE: The roles of endothelin-1 (ET-1) and oxidative stress causing vascular injury in the pathogenesis of diabetic neuropathy are debatable. The present study was undertaken to clarify the possible effects of oxidative stress and ET-1 in diabetic patients with and without peripheric neuropathy.

METHODS: We studied plasma ET-1, nitric oxide (NO), catalase, glutathione (GSH) levels of fifty (22 females, 28 males) patients with Type 2 diabetes in order to evaluate endothelial dysfunction and oxidative stress. The neuropathy types (motor, sensorial and sensorimotor), comorbid diseases, antidiabetic treatments, smoking, diabetes duration were also considered. Short McGill Pain Questionnaire (SF-MPQ) was also performed for patients with neuropathy.

RESULTS: There were no significant differences between patients with (n=23) and without (n=27) neuropathy with regards to demographic features except diabetic disease duration. The statistical analysis was done considering this difference. Although NO and ET-1 levels were higher, and catalase and GSH levels were decreased in neuropathic patients, no statistical significancy was found. We also couldn't find any correlations between the parameters and SF-MPQ scores.

CONCLUSIONS: Although there were no relationships between neuropathy and the studied parameters, we found lower levels of catalase and GSH as intracelluler antioxidants and higher NO and ET-1 as markers of endothelial injury in patients with neuropathy. Our data suggest that there is a need of further studies with larger study groups in order to clear out the role of endothelial injury and oxidative status in the pathogenesis of diabetic neuropathy....

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Journal Article 2010; 31(1): 73-86 PubMed PMID: 20150883 Citation  Keywords:  Adult, Brain Mapping, Cerebral Cortex:physiopathology, Dystonic Disorders:therapy, Female, Handwriting, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Models, Biological, Pilot Projects, Placebos, Radiation, Somatosensory Cortex:physiopathology, T.   

: Since the somatosensory system is believed to be affected in focal dystonia, we focused on the modulation of the primary somatosensory cortex (SI) induced by repetitive transcranial magnetic stimulation (rTMS) in order to improve symptoms of writer's cramp. Patients with writer's cramp (N=9 in the pilot study and N=11 in the advanced study) were treated with 30-minute 1 Hz real- or sham-rTMS of the SI cortex every day for 5 days. Before and after rTMS, 1.5 T fMRI was examined during simple hand movements. While in the pilot study the rTMS coil was navigated over the SI cortex with a maximum of blood oxygenation-level dependent (BOLD) signal induced by passive movement, patients in the advanced study had the coil above the postcentral sulcus. After real-rTMS, 4 pilot study patients and 10 advanced study patients experienced subjective and objective improvement in writing, while only minimal changes were observed after sham-rTMS. Patients involved in the active movement task exhibited a rTMS-induced BOLD signal increase bilaterally in the SI cortex, posterior parietal cortex and in the supplementary motor area (P<0.001 corrected). After sham-rTMS, no BOLD signal changes were observed. In conclusion, 1 Hz rTMS of the SI cortex can improve writer's cramp while increasing the cortical activity in both hemispheres. Handwriting improved in most patients, as well as the subjective benefit, and lasted for 2-3 weeks. The beneficial effects of rTMS paralleled the functional reorganization in the SI cortex and connected areas, reflecting the impact of somatosensory system on active motion control....

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Comparative Study 2010; 31(1): 147-154 PubMed PMID: 20150876 Citation  Keywords:  Acromegaly:etiology, Adenoma:complications, Adult, Female, GTP-Binding Protein alpha Subunits:genetics, Ghrelin:genetics, Growth Hormone-Secreting Pituitary Adenoma:complications, Humans, Male, Middle Aged, Mutation, RNA, Messenger:metabolism, Receptors, .   

OBJECTIVE: The purpose of this study was to investigate the relationship between the ghrelin or GHSR-1a mRNA levels and clinical characteristics and to confirm the effect of gsp mutations on ghrelin/GHSR-1a system in human GH-secreting pituitary adenomas.

METHODS: The expression levels of ghrelin, GHSR-1a mRNA were determined by SYBR green real-time fluorescent quantitative PCR. The gsp mutations in 43 cases of human GH-secreting pituitary adenomas were detected using PCR-DNA direct sequencing analysis. Clinical data were obtained from the medical records of 43 acromegalic patients who had GH and IGF-1 assays in the same laboratory.

RESULTS: The expression of GHSR-1a correlated positvely with tumor size (R=0.411, p=0.006) and invasiveness (p<0.05). In contrast, ghrelin mRNA levels correlated positively only with tumor size (R=0.331, p=0.030) but not with tumor invasiveness (p>0.05). The expression level of GHSR-1a mRNA was significantly higher in gsp positive adenomas than in negative adenomas (p<0.05). Whereas, there was no significant difference in the expression of ghrelin mRNA between gsp mutation-positive and -negative adenomas (p>0.05). Additionally there was a significant positve correlation between the ghrelin and GHSR-1a mRNA expression levels in gsp-positive (R=0.553, p=0.040) or -negative adenomas (R=0.489, p=0.007).

CONCLUSIONS: GHSR-1a correlated positively with tumor size and invasiveness, while ghrelin correlated positively only with tumor size. Gsp mutations may upregulate the expression of GHSR-1a mRNA and have no effect on ghrelin mRNA levels in human GH-secreting pituitary adenomas....

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Evaluation Studies 2010; 31(1): 113-116 PubMed PMID: 20150872 Citation  Keywords:  Adult, Aged, Biomarkers, Tumor:blood, Carcinoma:blood, Carcinoma, Non-Small-Cell Lung:blood, Humans, Lung Neoplasms:blood, Male, Middle Aged, Neoplasm Staging:methods, Neopterin:blood, Predictive Value of Tests, Prognosis, Prostatic Neoplasms:blood, alpha.   

OBJECTIVE: Increased serum levels of alpha-1 antitrypsin (alpha1-AT) and neopterin were observed in many diseases including different types of cancer. The aim of this work is to determine alpha1-AT and neopterin serum levels in newly diagnosed untreated non-small cell lung and prostate cancer patients and to test their relation to cancer staging.

METHODS: Radial Immunodiffusion and ELISA methods were used to determine alpha1-AT and neopterin serum levels, consequently.

RESULTS: alpha1-AT and neopterin mean serum levels were found to be elevated in non-small-cell lung and prostate cancer patients. In non-small cell lung cancer patients alpha1-AT was 454.5+/-129.2 mg/dL (p<0.0005) and neopterin was 7.9+/-4.2 ng/mL (p<0.0005). In prostate cancer patients alpha1-AT was 462.7+/-116.9 mg/dL (p<0.0005) and neopterin was 8.1+/-3.1 ng/mL (p<0.0005). These elevated levels were significantly correlated with the stage of cancer. The mean serum level of alpha1-AT in stages I, II, III, and IV among non-small cell lung cancer patients were 305.1, 453.6, 490.3 and 616.0 mg/dL respectively, and the mean serum levels for neopterin were 4.0, 7.0, 8.1 and 14.9 ng/mL, correspondingly. The mean serum level of alpha1-AT in stages A, B, C, and D among prostate cancer patients were 342.9, 418.5, 467.8 and 593.5 mg/dL respectively and the mean serum levels for neopterin were 4.9, 6.6, 8.7 and 11.6 ng/mL, correspondingly.

CONCLUSIONS: Based on the above mentioned findings alpha1-AT and neopterin serum levels should be considered in the follow up as well as in the prognosis of cancer patients....

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Journal Article 2010; 31(1): 155-160 PubMed PMID: 20150868 Citation  Keywords:  Aged, Aged, 80 and over, Biomarkers:analysis, Body Mass Index, Bone Density, Bone Remodeling:physiology, Bone and Bones:metabolism, Calcium:analysis, Female, Humans, Leptin:blood, Male, Middle Aged, Osteoporosis:blood,.   

OBJECTIVE: Clinical data have suggested that obesity protects against osteoporosis. Leptin, mainly secreted by white adipose tissue, might be involved by mediating an effect on bone metabolism. This study was conducted to investigate a possible relationship of leptin and bone turn-over in postmenopausal women with osteoporosis.

METHODS: We measured bone mineral density (BMD), serum leptin levels and markers of bone metabolism, including osteocalcin and cross-laps in 44 patients with osteoporosis. The main group consisted of 32 postmenopausal women.

RESULTS: Mean serum leptin was 13.1 microg/L and showed no statistically significant difference to the levels measured in a collective of normal persons adjusted for age and BMI. When related to serum cross-laps as markers of bone resorption, a positive correlation (p<0.05) was observed, whereas no correlation with osteocalcin could be seen.

CONCLUSIONS: A dual control of bone formation by leptin is assumed: This involves local mechanisms acting on osteoblasts and a central inhibitory effect on bone metabolism via a hypothalamic relay. Our data indicate that the net effect of circulating leptin may cause bone loss and is significantly related to high-turnover serum bone markers, at least in postmenopausal women with osteoporosis....

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