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Historical Article 2012; 33(4): 357-360 PubMed PMID: 22936255 Citation  Keywords:  Chronobiology Discipline:history, Chronobiology Disorders, History, 20th Century, History, 21st Century, Humans, Terminology as Topic,.   

: Chronomedicine may be conceptualized as dealing with the prevention, causation, diagnosis, and treatment of diseases in humans with a particular focus on the role "time" [Greek: chrónos] plays in our physiology, endocrinology, metabolism and behavior at many organizational levels. While it has been used as a term and somewhat pursued as a discipline for decades, it appears that chronomedicine has captured a broader interest as a promising specialty only more recently. This commentary addresses roots of chronomedicine in the 1900s and perspectives for chronomedicine in the 21st century. Classical terms of chronobiology, e.g., Zeitgeber, melatonin and circadian, may be traced back to Aschoff, Lerner, and Halberg, respectively, but who actually coined the term "chronomedicine" and used it first in a publication remains unclear. Importantly, it could be(come) rather straightforward to transfer abundant insights gained from chronobiology to strategies in chronomedicine as animal models have been increasingly developed to understand human health and disease. Perspectively, chronomedicine should comprise "clinical chronomedicine" (individual-based) and "preventive chronomedicine" (population-based). Overall, due to the "maturing" of chronomedicine as a field, the near future might bring a section dedicated to chronomedicine in existing journals, or even a "Journal of Chronomedicine" as vectors of ideas and research....

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Journal Article 2012; 33(4): 446-452 PubMed PMID: 22936253 Citation  Keywords:  Animals, Arachidonic Acids:pharmacology, Behavior, Animal:drug effects, Central Nervous System Sensitization:drug effects, Dopamine Agents:pharmacology, Drug Administration Schedule, Drug Interactions, Male, Mesencephalon:drug effects, Methamphetamine:pha.   

OBJECTIVES: In our previous studies we found that both acute administration of CB1 receptor agonist methanandamide and repeated methanandamide pre-treatment prior to methamphetamine challenge dose elicited increase in the CB1 receptor mRNA expression in the mouse mesencephalon. As a reciprocal cross-talk is reported between the cannabinoid CB1 and dopamine receptors, that are highly co-localized on brain neurones, we targeted possible changes in relative expression of dopamine D1 and D2 receptor mRNA in mesencephalon in mice sensitized by repeated treatments to methamphetamine stimulatory effects and cross-sensitized to methamphetamine by cannabinoid CB1 receptor agonist methanandamide pre-treatment.

METHODS: To confirm development of behavioural sensitization or cross-sensitization, respectively, we observed changes in locomotion using the open field test. Mice were treated repeatedly with either methamphetamine or methamphetamine after repeated pre-treatment with methanandamide. After each measurement of locomotion one third of animals were sacrificed and the brain was stored. RNA was isolated from the midbrain and used for reverse transcription and subsequent real-time PCR.

RESULTS AND CONCLUSION: As in many of our earlier studies with the same dosage regimen we found in the behavioural part both development of sensitization to methamphetamine stimulatory effects after repeated treatment and cross-sensitization to them by pre-treatment with cannabinoid receptor CB1 agonist methanandamide. Real-time PCR analyses showed an increase in D1 receptor mRNA expression after the first dose of methamphetamine (that persisted also after the last dose of methamphetamine) and after the first dose of methanandamide (which also persisted after the methamphetamine challenge dose). In opposite a significant decrease in D2 receptor mRNA expression both after the first dose of methamphetamine and methanandamide (that persisted also after the methamphetamine challenge doses) was registered. Thus, our results suggest that both methamphetmine and methanandamide treatment can provoke changes in dopamine receptor density in mouse mesenpcephalon, the increase in D1 and decrease in D2 receptor subtypes....

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Comparative Study 2012; 33(4): 425-430 PubMed PMID: 22936252 Citation  Keywords:  Adult, Analysis of Variance, Biomarkers:metabolism, Computer Simulation, Female, Humans, Hydrocortisone:metabolism, Male, Maze Learning, Reaction Time, Reference Values, Saliva:metabolism, Self-Assessment, Sex Factors, Spatial Behavior, Stress, Psychologi.   

OBJECTIVES: Spatial learning is shown to be influenced by acute stress in both human and other animals. However, the intricacies of this relationship are unclear. Based on prior findings we hypothesized that compared to a control condition, a social stress condition would not affect spatial learning performance despite elevated biochemical markers of stress.

METHODS: The present study tested the effects of social stress in human males and females on a subsequent spatial learning task. Social stress induction consisted of evaluative stress (the Trier Social Stress Test, TSST) compared to a placebo social stress.

RESULTS: Compared to the placebo condition, the TSST resulted in significantly elevated cortisol and alpha amylase levels at multiple time points following stress induction. In accord, cognitive appraisal measures also showed that participants in the TSST group experienced greater perceived stress compared to the placebo group. However, there were no group differences in performance on a spatial learning task.

CONCLUSION: Our findings suggest that unlike physiological stress, social stress does not result in alterations in spatial learning in humans. It is possible that moderate social evaluative stress in humans works to prevent acute stress-mediated alterations in hippocampal learning processes.....

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Journal Article 2012; 33(3): 347-355 PubMed PMID: 22635096 Citation  Keywords:  Adolescent, Age of Onset, Cognition:physiology, Cognition Disorders:diagnosis, Communication Disorders:diagnosis, Executive Function:physiology, Female, Humans, Language Disorders:diagnosis, Male, Neuropsychological Tests, Phonetics, Schizophrenia:physiop.   

OBJECTIVE: Although formal thought disorder and cognitive impairment are key features of schizophrenia, only a few studies evaluated both in adolescent population.

METHOD: 32 inpatients with early-onset schizophrenia spectrum disorders (SSD) and 32 matched healthy controls were studied with Thought, Language and Communication Scale and battery of neurocognitive tests and SSD subjects were also assessed with Positive and Negative Syndrome Scale and Clinical Global Impression Scale.

RESULTS: Patients presented impairment in both cognitive functioning and formal thought processes. Communication disturbances correlated with executive and verbal fluency dysfunction.

CONCLUSION: Communication disturbances in adolescent SSD patients may have both dysexecutive and dyssemantic origin....

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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.

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.

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).

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.

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.

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).

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): 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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