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Journal Article 2012; 33(3): 340-346 PubMed PMID: 22635095 Citation  Keywords:  Adult, Aged, Bromocriptine:administration & dosage, Dopamine Agonists:administration & dosage, Dose-Response Relationship, Drug, Ergolines:administration & dosage, Female, Heart Valve Diseases:chemically induced, Humans, Male, Middle Aged, Pituitary Neopl.   

OBJECTIVES: Prolactinoma is the most common pituitary adenoma, and dopamine agonists( BRC, and CAB) is the primary therapy. Recently, the increased prevalance of cardiac valvular disease in patients treated with DAs for Parkinson's disease has raised concerns about the safety of this drug in patients with prolactinoma. CAB and pergolide are frequently reported to cause valvulopathy, there are very few studies showing this side effect in BRC administiration which has less potent agonism of 5-HT2B receptors. Male patients who are known to have higher prevalance of macroadenomas compared to women. The dosage of DAs administered were rarely evaluated.r />r /> METHODS: We performed a retrospective chart to evaluate the medical management and treatment outcomes of male patients with macro/giant prolactinomas. We evaluated 22 patients with prolactinoma managed with DAs therapy alone for at least 1 year. All patients were followed for a mean of 61 months. Pretreatment echocardiographic examination were not available at that time.r />r /> RESULTS: None of them had any resistance or intolerance to DAs. The mean tumor shrinkage was 62%. In three patients the macroprolactinoma disappeared, in two patients the tumor shrinkage was 93% and 70%. The DAs therapy was discontinued in these patient. After a follow up neither MRI showed a recurrence or enlargement of the adenoma, nor prolactin levels showed any elevation. The echocardiography were performed at the last visit of each patient and no valvulopathy in any of the patients on DAs therapy were detected.r />r /> CONCLUSIONS: DAs are effective, and safe for valve morphology with mean cumulative doses of 155 mg CAB, and 7 301 mg BRC in patients with macroprolactinoma....

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Journal Article 2012; 33(3): 331-339 PubMed PMID: 22635094 Citation  Keywords:  Adolescent, Body Height:physiology, Body Mass Index, Child, Child, Preschool, Female, Ghrelin:blood, Growth Disorders:metabolism, Human Growth Hormone:deficiency, Humans, Male, Neurosecretory Systems:metabolism,.   

BACKGROUND: The role of endogenous ghrelin in the growth process of children is unclear. The aim of the present study was to assess ghrelin concentrations in children with growth hormone deficiency (GHD), neurosecretory dysfunction (NSD) and idiopathic short stature (ISS) in comparison to healthy controls.r />r /> MATERIAL: One hundred and forty seven children (61 girls and 86 boys), aged 3.7-16.8 years (mean±SD: 10.7±3.44 years) with short stature (below -2.0 SD) were qualified into the study. In each child, fasting ghrelin and insulin-like growth factor type I (IGF-I) concentrations were measured and growth hormone (GH) secretion was assessed after falling asleep and during two GH-stimulating tests. According to maximal GH concentrations, children were qualified into GHD, NSD and ISS group. Additionally, depending on biological development, the children were divided on younger and older subgroups. The control group consisted of 19 healthy children with normal height and body mass.r />r /> RESULTS: Ghrelin concentrations in GHD (1847.5±1444.3 pg/mL) and NSD (1809.3±983.5 pg/mL) were significantly higher than in ISS (1218.1±646.8 pg/mL) and in Controls (924.9±318.4 pg/mL). A comparison of ghrelin concentrations in older and younger children within the same diagnostic group, showed statistically higher ghrelin levels in younger than in older children (except of NSD group, in which the difference reached the border of statistical significance).r />r /> CONCLUSIONS: Ghrelin concentration is elevated in GHD and NSD children. Independently of GH and IGF-I secretion disorders type, ghrelin concentrations decrease with the children' age. The higher concentration of ghrelin in ISS than in Controls suggests the presence of GH-independent factors increasing ghrelin secretion by X/A cells in the gastric oxyntic mucosa....

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Journal Article 2012; 33(3): 321-330 PubMed PMID: 22635093 Citation  Keywords:  Adult, Case-Control Studies, Databases, Genetic, Female, Genetic Predisposition to Disease:genetics, Genotype, Humans, Insulin Receptor Substrate Proteins:genetics, Male, Middle Aged, Polymorphism, Single Nucleotide:genetics, Schizophrenia:genetics,.   

OBJECTIVES: Since there are clear indications that schizophrenia is a systemic disorder, we sought for a common molecular basis for schizophrenia abnormalities in brain and body. Our hypothesis was that an impaired insulin and insulin-like growth factor signalling in cells might underlie changes in both brain and body in schizophrenia. In this regard, the insulin receptor substrates 1-4, linking both the insulin and insulin-like growth factor-1 receptors with intracellular pathways, might be of interest to study genetically. In the present study, we chose to study the insulin receptor substrate-3 (IRS-3) gene as a candidate gene in schizophrenia.r />r /> METHODS: The IRS-3 gene of 93 patients with the diagnosis of schizophrenia according to DSM-IV criteria and 57 healthy control subjects was screened for DNA sequence variations, followed by case-control analyses of total 10 detected polymorphisms.r />r /> RESULTS: The A/G genotype of the single nucleotide polymorphism (SNP) rs117078492 in the IRS-3 gene occurred in 5.3% of the control subjects compared with in 0% of the patients (p=0.05). Similarly, the haplotypes 5 and 3X, constructed from polymorphisms in the IRS-3 gene and including the A allele of this A/G SNP, occurred only in the control subjects and not in the patients (5.3% vs 0%, p=0.05).r />r /> CONCLUSION: Our findings suggest that individuals carrying the A allele of this A/G SNP in the IRS-3 gene as well as the estimated haplotypes 5 or 3X including this A allele, have a protection against schizophrenia development....

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Journal Article 2012; 33(3): 318-320 PubMed PMID: 22635092 Citation  Keywords:  Animals, Chronobiology Phenomena:physiology, Circadian Rhythm:physiology, Light, Melatonin:physiology, Models, Animal, Photoperiod, Translational Medical Research:methods,.   

: That light and melatonin rhythms provide both clock and calendar information in humans and numerous other species is beyond dispute; this holds true for all stages of life, including the very early ones. Experimental evidence elucidates that exposure to light and melatonin titres are keys for the very development of circadian and seasonal rhythms. As evinced by a 2011 publication in Nature Neuroscience such awareness could impact considerably on the design and conduct of experimental studies as well as their subsequent analyses, interpretations and comparisons. Therefore "when and how experimental animals were bred, developed and raised" may be critical when experimenting with animals generally, and not just rodents. As long as the suggested imprinting of circadian system stability via light cues is not falsified, the perinatal season or perinatal experimental light:dark [L:D] conditions that an animal was kept under should be routinely recorded, published and considered in analysing and interpreting study data....

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Journal Article 2012; 33(3): 314-317 PubMed PMID: 22635091 Citation  Keywords:  Adult, Child, Child Development, Circadian Rhythm, Humans, Infant, Infant, Newborn, Light, Mood Disorders:epidemiology, Neoplasms:epidemiology, Photoperiod, Seasons,.   

: Thought-provoking experimental evidence suggests that perinatal light exposure may imprint circadian clocks with lasting effects on the alignment and the stability of circadian rhythms later in life. Assuming that exposure to light early in life could determine the stability of an individual's circadian system later in life, the present hypothesis proposes that time of year and location of birth (i.e., season and latitude) and thus differential Zeitgeber strengths may be key contributors to a person's susceptibility of developing mood disorders like seasonal affective disorder (SAD) and common internal cancers such as those of breast and prostate. Consequently, when and where people are born might critically predispose them to both mood disorders and internal cancers, and may affect the onset and course of such illnesses. This paper develops a causal framework and presents suggestions for rigorous tests of the associated corollary and predictions. It does not escape our attention that links between the perinatal Zeitgeber strength of light and its effects on the stability of circadian systems later in life could have a role to play in affecting long-term health beyond cancer and mood disorders - mostly in adults but also in children....

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Historical Article 2012; 33(3): 304-313 PubMed PMID: 22635090 Citation  Keywords:  Animals, Congenital Abnormalities:history, History, 19th Century, History, 20th Century, History, Ancient, Humans, Neuroendocrinology:history, Teratology:history,.   

: Teratology is the science of congenital developmental disorders (CDDs), overt or latent defects of the organism resulting from the effect of internal and external factors on developmental processes. In this article the significance and position of present-day teratology is discussed in the context of development of this branch of science and related disciplines. The authors present an updated overview of the most important milestones and stages of the development of teratology. Based on the analysis of the historical development of theses and theories that represent a decisive contribution to this field, we present a survey of the fundamental principles of experimental and clinical teratology. The aim of observing these principles is to get insight into developmental relations and to understand mechanisms of action on the level of cell populations (elementary morphogenetic processes), tissues and organs. It is important to realize that any negative intervention into the normal course of these processes, either on genetic or non-genetic basis, inevitably leads to a sequence of subsequent changes resulting in the development of congenital developmental disorders. Despite modern approaches of molecular biology and genetics, along with top diagnostic techniques, we are still not able to identify the actual cause in more than 50% of all congenital defects. One-half of the unidentified cases are referred to as "multifactorial", a term that is rather ambiguous. It either means that some of the basic principles of teratogenesis still escape our attention, or the interpretation of some of the well known principles might be misleading. A third possibility is rather pessimistic. The development of the individual is so sophisticated and dependent on a delicate network of a multitude of factors mutually affecting each other that it is extremely prone to give rise to a plethora of spontaneous errors which are unpredictable and impossible to prevent. Nevertheless, the long and complicated history of scientific endeavour has yielded considerable present-day knowledge on causes and mechanisms of CDDs, a history whose beginnings date back to antiquity....

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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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