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Journal Article 2005; 26(3): 242-246 PubMed PMID: 15990729 Citation  Keywords:  Adolescent, Biomarkers:blood, C-Reactive Protein:metabolism, Child, Endothelium, Vascular:immunology, Female, Humans, Hypertension:etiology, Intercellular Adhesion Molecule-1:blood, Interleukin-1:blood, Interleukin-6:blood, Lipids:blood, Male, Obesity:com.   

OBJECTIVES: It has been suggested that a rise in blood pressure (BP) causes low-grade inflammation of the endothelium which, in turn, may be responsible for further damage of endothelium and worsening of BP control. The aim of the study was to evaluate serum levels of inflammation and endothelial activation markers in children with obesity-related hypertension and normotensive controls in relation to other traditional risk factors of arterial hypertension.r />r /> METHODS: Plasma insulin, glucose, C-reactive protein (CRP), fibrinogen (FB) interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and lipids levels were determined in 50 children with obesity-related hypertension and 143 obese children with normal BP. Insulin resistance was assessed by the homeostasis model.r />r /> RESULTS: Children with hypertension had significantly higher levels of all inflammatory markers as well as endothelial activation indices compared with normotensive subjects. In the stepwise regression model significant independent correlates for systolic BP were CRP, FB, VCAM-1, HOMA IR, LDL cholesterol and fat mass, whereas CRP, IL-6, ICAM-1, FB, LDL and HDL cholesterol were the determinants of diastolic BP in children with obesity-related hypertension.r />r /> CONCLUSION: These results indicate that low-grade inflammation and endothelial dysfunction are closely involved in the pathogenesis of obesity-related hypertension relatively early in life....

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Journal Article 2005; 26(3): 237-241 PubMed PMID: 15990728 Citation  Keywords:  Animals, DNA:chemistry, Entropy, Evolution, Molecular, Humans, Models, Chemical, Nucleic Acid Conformation, Peptides:chemistry, Promoter Regions, Genetic, Protein Binding, Protein Conformation, Transcription Factors:chemistry,.   

PROBLEM: Gerontology observations show that ageing of organism is accompanied by the decrease of the chromatin activity and slowing down of the protein synthesis. Natural regulatory oligopeptides and their synthetic analogues take part in the activation of chromatin and normalise rate of the protein synthesis in cultured tissues. Regulatory peptides significantly enhance longevity.r />r /> OBJECTIVES: The objective of this work is to find a possible molecular mechanism by which the regulatory peptides influence the part of genetic system is responsible for initiation of protein synthesis in higher organisms.r />r /> METHODS: An interdisciplinary approach was used to address the problem. The work involved not only medical scientists and biologists, but also specialists in biopolymer chemistry, and mathematicians for statistical analysis of information interaction of amino acid and nucleotide sequences.r />r /> CONCLUSIONS: The structures and metrics of peptides and the DNA double-helix cause the recognition and complementary binding of a regulatory peptide with DNA functional groups at the interface of the major groove. We have used complementary binding model to find a possible base pair sequence ATTTTC for specific binding of synthetic tetrapeptide epitalon. This base pair block and its reverse complement were found repeatedly in the promoter region of telomerase. A comparison of statistical information content of peptides and oligonucleotide sequences shows that these two classes of biopolymers are information carriers and. exchange the information to initiate the gene transcription....

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Journal Article 2005; 26(3): 231-236 PubMed PMID: 15990727 Citation  Keywords:  Animals, Brain Chemistry:immunology, Cell Extracts:chemistry, Cytokines:analysis, Detergents, Enzyme-Linked Immunosorbent Assay:methods, Interferon-gamma:analysis, Interleukin-10:analysis, Kidney:chemistry, Lipopolysaccharides:pharmacology, Liver:chemistr.   

OBJECTIVES: Determination of protein cytokines in local tissues would help to evaluate their local role in health, sickness behavior and immune-mediated diseases. Therefore, developing a simple quantitative method of protein cytokines in tissues/organs is highly important.r />r /> METHODS: Mouse tissues were collected following intraperitoneal administration of endotoxin-free PBS or lipopolysaccharide. A mild detergent, 0.1% Igepal, was added in a buffer to enhance cytokines extraction. The tissues were then disrupted, homogenized, centrifuged and the supernatants were collected and assayed using solid-phase immunoassays.r />r /> RESULTS: The presence of 0.1% Igepal extracted significantly more TNF-alpha from liver (322%: p<0.01), brain (358%: p<0.05), lungs (1600%: p<0.01), and more IL-10 from liver (220%: p<0.001), brain (4650%: p<0.001) than PBS alone. On the other hand, using 0.1% Igepal did not increase IFN-gamma extraction from liver, spleen, brain, lungs, skin and kidneys more than PBS alone. Furthermore, i.p. administration of LPS induced a differential milieu of cytokines. LPS increased significantly the production of TNF-alpha, IFN-gamma, and IL-10 from liver (521%, 123%, 72%: p<0.01, 0.04, 0.04), brain (470%, 122%, 280%: p< 0.01, 0.03, 0.01), peritoneal lavage (p<0.001) and blood (p<0.001). However, the pattern of increase was different for the above cytokines in spleen, skin, lungs and kidneys.r />r /> CONCLUSIONS: The extraction of protein cytokines from tissues was superior with addition of mild detergent. Furthermore, our results showed a differential cytokines response to LPS with respect to tissue and cytokine type. This method should provide an important tool for studying local protein cytokines in behavioral pattern, sickness behavior, and immune-mediated diseases as well as to determine local therapeutic efficacy of immunomodulatory drugs....

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Journal Article 2005; 26(3): 225-230 PubMed PMID: 15990726 Citation  Keywords:  Animals, Blood Glucose:drug effects, Cholinesterase Inhibitors:pharmacology, Denervation, Entorhinal Cortex:cytology, Excitatory Amino Acid Agonists, Hippocampus:cytology, Ibotenic Acid, Male, Microinjections, Neostigmine:pharmacology, Neural Pathways, Ra.   

OBJECTIVE: Microinjectin of neostigmine, an inhibitor of acetylcholine esterase, into the rat hippocampus elicited stress-like responses reflected by the release of adrenocorticotropic hormone (ACTH) and blood glucose elevations. The entorhinal cortex is regarded as an interface between the hippocampus and neocortex. The current study was designed to examine the role of the entorhinal cortex in regulation of blood glucose elevation induced by hippocampal neostigmine injection.r />r /> MATERIAL AND METHODS: We produced the entorhinal cortex lesions in 9 week-old male Wistar rats by the bilateral injections of the cell-selective neurotoxin, ibotenic acid (15microg/microl). Two weeks after the injections, neostigmine methylsulfate (sigma, 5x10(-8) mol) was microinjected into the rat hippocampus in a volume of 1microl for 1min using a CMA/100 microinjection pump. Plasma ACTH levels were measured by radioimmunoassay. Plasma glucose concentrations were determined by the immobilized enzyme membrane/H2O2 method with a compact glucose analyzer Antsense II (Bayer Medical Co.Ltd,Tokyo, Japan).r />r /> RESULTS: Compared with sham-operated control rats, the entorhinal lesions produced by ibotenic acid significantly attenuated the elevations of blood glucose evoked by the microinjection of neostigmine into the hippocampus. However, no significant difference of plasma ACTH in response to the injection was observed between the entorhinal-lesioned rats and controls.r />r /> CONCLUSION: The results of the present study indicate that the entorhinal cortex plays a role in the central nervous systems regulation of blood glucose and may be involved in a stress response presumably via an alternative pathway....

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Journal Article 2005; 26(3): 219-224 PubMed PMID: 15990725 Citation  Keywords:  Adolescent, Adult, Cerebral Cortex, Cerebral Ventricles, Choristoma, Electroencephalography, Epilepsy:epidemiology, Evoked Potentials, Somatosensory, Female, Humans, Hydrocephalus:epidemiology, Incidence, Magnetic Resonance Imaging, Median Nerve:physiolog.   

OBJECTIVES: Developmental cerebral dysplasias are frequent causes of epilepsy. The early stage of gestation, mainly the period of neural crest separation and neuroblast migration (disturbance of midline structures, heterotopias, cortical dysplasias and disturbance of the ventricular and vascular formation), may be considered as a cause of serious cerebral dysplasia. The aim of the study was focused on frequent simultaneous occurrences of epileptic seizures and the defect or abnormality of the ventricular system - cavum septi pellucidi (CSP).r />r /> MATERIAL AND METHOD: In our study the clinical symptoms, EEG and somatosensory evoked potentials (SEP's) following median nerve stimulation and MRI pictures in the group of patients with CSP (n= 35), were analyzed. In the SEP analysis, a control group of normal, healthy volunteers (n = 40) and a group of age matched patients with epileptic seizures of different origin, without structural lesions evident on MRI (n=21), were used.r />r /> RESULTS: Analysis of the patient population with CSP (CSP was confirmed by MRI) showed that approximately in 2/3 cases, different types of cranio-cerebral dysplasias were evident on MRI. More than 2/3 of the patients with CSP showed epilepsy and an abnormal EEG record, however, focal EEG changes were seen more frequently in the group of patients with epilepsy without CSP, than in patients with CSP. The SEP's in patients with CSP showed a statistically significant prolongation of latency of thalamic P15 waves, however these changes were not present in the group of patients with epilepsy of a different origin.r />r /> CONCLUSIONS: In a group of patients with CSP, dysplastic MRI changes, together with the prolongation of thalamic wave latencies according SEP, were examined. These clinical symptoms may be considered the result of disturbances of early gestation and of lesions of midline structures. CSP became an interesting model opportunity for us, and allowed for the clinical, MRI and electrophysiological examination of developmental cerebral dysplasias. We believe that there is an important role for septal and diencephalic midline structures in cerebral electrogenesis, and possibly in the origin of epileptic seizures too....

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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.r />r /> OBJECTIVES: The aim of our study was to determine the survivin expression in different types of pituitary adenomas.r />r /> 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.r />r /> 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.r />r /> 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): 205-208 PubMed PMID: 15990722 Citation  Keywords:  Animals, Antipsychotic Agents:pharmacology, Dibenzothiazepines:pharmacology, Glucose:pharmacology, Insulin:metabolism, Islets of Langerhans:drug effects, Male, Organ Culture Techniques, Piperazines:pharmacology, Quetiapine Fumarate, Rats, Rats, Wistar, Ri.   

OBJECTIVE: In the light of the recent finding that the atypical antipsychotics clozapine and olanzapine have a stimulatory effect on basal insulin release in vitro, the influence on insulin release of three other atypical agents; quetiapine, risperidone and ziprasidone, was examined.r />r /> METHODS: The effect of each atypical antipsychotic in a concentration of 10(-6) M was investigated on both basal and glucose-stimulated insulin release from isolated rat pancreatic islets.r />r /> RESULTS: No difference in effect on insulin release was found for any of the three atypical antipsychotic substances compared to controls without antipsychotics, either in basal or in glucose-stimulated insulin release.r />r /> CONCLUSION: This study demonstrates that the main compounds of quetiapine, risperidone and ziprasidone do not increase insulin release from isolated pancreatic islets, which stands in clear contrast to what has been found previously for clozapine and olanzapine. Thus, atypical antipsychotics seem to differ in their effect on insulin release in vitro....

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