Search NEL Online

Journal Article 2005; 26(4): 423-430 PubMed PMID: 16135997 Citation  Keywords:  Attention Deficit Disorder with Hyperactivity:genetics, Biomarkers, Brain Chemistry:genetics, Genetic Markers, Humans,.   

: ADHD (attention hyperactivity disorder) is a polygenetic disorder with various candidate genes. At this time, more than thirty dopaminergic, noradrenergic, serotonergic and GABA-ergic genes are known. The research of only some candidate genes (DRD4, DAT, DRD5, DBH, 5HTT, HTR1B and SNAP25) brought relatively consistent results confirming the heredity of ADHD syndromes. The results of research of other genes (DRD2, DRD3, MAO, ADR2A, GABA A3, GABA B3) are not clear yet. This paper summarizes the most important genetic data in correlations with biochemical periphery parameters (especially for DBH, HVA, MHPG, serotonin). Hypothetically, certain subgroups of ADHD may be identified by correlation of biochemical characteristics and some candidate genes. The paper discusses some implications for future research. Review....

Read abstract  Full text PDF

Journal Article 2005; 26(4): 293-296 PubMed PMID: 16135994 Citation  Keywords:  Adult, Energy Metabolism:physiology, Female, Humans, Insulin:blood, Intracellular Signaling Peptides and Proteins:blood, Leptin:blood, Middle Aged, Neuropeptide Y:blood, Neuropeptides:blood, Obesity:blood, Orexins, Radioimmunoassay,.   

OBJECTIVE: It has been reported that the peptides such as orexins, neuropeptide Y (NPY) and leptin may play an important role in the regulation of appetite and energy metabolism. The interaction between leptin, orexins and NPY, as well as between peptides and insulin and cortisol in the different nutritional states have been investigated in animals. However, at present this relationship is poorly understood in humans.

RESEARCH METHODS: Material consisted of 36 obese women and 16 lean women. Plasma orexin A, orexin B, neuropeptide Y (NPY), leptin, insulin concentrations were measured with RIA methods.

RESULTS: Plasma orexin A concentrations were significantly lower in obese women as compared with control group. Plasma orexin A was significantly lower in severe obesity (BMI > 40 kg/m2) than that in moderate obesity (BMI < 40 kg/m2). Plasma orexin B concentrations did not change. However, plasma NPY, leptin and insulin levels were markedly higher in obese women, especially in severe obesity.

CONCLUSIONS: Our results confirmed the thesis that orexin A, NPY, leptin play an important role in the regulation of energy metabolism in humans. In obesity the activity of these peptides is disturbed....

Read abstract  Full text PDF

Journal Article 2005; 26(3): 257-260 PubMed PMID: 15990732 Citation  Keywords:  Adult, Aged, Empty Sella Syndrome:blood, Female, Hormones:blood, Humans, Hypoglycemia:blood, Hyponatremia:blood, Hypopituitarism:blood, Hypothyroidism:blood, Middle Aged, Turkey:epidemiology,.   

: Sheehan syndrome (SS) or post-partum pituitary necrosis is a pituitary insufficiency secondary to excessive post-partum blood losses. SS is a very significant cause of maternal morbidity and mortality in developing countries although it is a rarity in developed countries in which obstetrical care has been improved. In this study, we reviewed 20 cases retrospectively who were diagnosed as SS in our clinic. The patients aged 40 to 65 years with a mean age of 51.12 +/- 9.44 years (mean +/- SD). Time to make a definitive diagnosis of the disease ranged between 5 and 25 years with a mean of 16.35 +/- 4.74 years. Three of our patient (15%) had a previous diagnosis of SS. Three patients (15%) were referred to emergency service for hypoglycemia, three patients (15%) for hypothyroidism and one patient (5%) for hyponatremia. Dynamic examination of the pituitary revealed GH, Prolactin, FSH, TSH and ACTH insufficiency in all of the patients. One of our patients had a sufficient LH response to LHRH challenge. All of the patients were imaged with pituitary MRI. Eleven patients had empty sella and 9 patients had partial empty sella. SS is still a common problem in our country, especially in rural areas. Considering the duration of disease, important delays occur in diagnosis and treatment of the disease....

Read abstract  Full text PDF

Journal Article 2005; 26(3): 247-252 PubMed PMID: 15990730 Citation  Keywords:  Animals, Copper:chemistry, Gonadotropin-Releasing Hormone:chemistry, Metals, Heavy:chemistry, Nickel:chemistry, Nuclear Magnetic Resonance, Biomolecular, Protons, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization,.   

: MALDI-TOF mass spectrometry, 1H NMR spectrometry, the continuous variation method and molecular modeling by MM3 calculation confirmed our earlier studies showing that gonadotropin-releasing hormone (GnRH) forms complex with copper(II) ion with the binding ratio 1:1. The copper(II) complex formed at physiological pH has a square planar configuration and GnRH complexes with nickel(II) and cobalt(II) ions are less stable than that of copper(II)....

Read abstract  Full text PDF

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.

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.

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.

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....

Read abstract  Full text PDF

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.

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.

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.

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....

Read abstract  Full text PDF

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.

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).

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.

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....

Read abstract  Full text PDF

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).

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.

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.

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....

Read abstract  Full text PDF