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Case Reports 2013; 34(5): 343-346 PubMed PMID: 23922039 Citation  Keywords:  Aged, Anticoagulants:adverse effects, Cerebral Amyloid Angiopathy:complications, Cerebral Hemorrhage:chemically induced, Hematoma:complications, Humans, Male,.   

: The incidence of anticoagulant treatment (AT)-related intracerebral hemorrhage (AT-ICH) is increasing in consequence of the increased incidence of ischemic stroke due to an aging population. AT-ICH is associated with a risk of ongoing bleeding, death, or disability. Cerebral amyloid angiopathy (CAA), a common pathological finding among the elderly that is associated with macro- and microscopic hematoma development, might increase the risk of ICH. We report a rare case of contralateral delayed hematoma in the context of CAA secondary to acute ICH after AT for intracerebral ischemic stroke....

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Journal Article 2013; 34(5): 347-358 PubMed PMID: 23922038 Citation  Keywords:  Amygdala:drug effects, Animals, Association Learning:drug effects, Behavior, Animal:drug effects, Conditioning (Psychology):drug effects, Estrogen Receptor alpha:metabolism, Fear:drug effects, MAP Kinase Signaling System:drug effects, Male, Methyl-CpG-Bin.   

OBJECTIVES: Benzyl Butyl Phthalate (BBP) is an industrial plasticizer that has an unknown action in the central nervous system. Phthalates have recently been associated with behavioral actions that are linked to their endocrine disrupting properties. The purpose of this study was to investigate the behavioral and molecular effects of BBP treatment in male rats.

DESIGN: Male rats were chronically exposed to BBP in the drinking water (5.0 ppm and 10.0 ppm) throughout adolescence and into the adult phase of life. Their behavior was then assessed in a learning and memory task (fear conditioning), open field exploration and a test of sociability.

RESULTS: BBP treated rats showed decreased freezing in fear conditioning, no changes in open field exploration, and increased aberrant social behavior. Rats were sacrificed at post natal day 140 and blood and brains were harvested and processed. We found increased hormonally active estrogen, 17-β estradiol, in the serum of BBP treated rats. BBP treatment also induced changes in amygdalar proteins related to synaptic plasticity including decreased MeCP2 levels that correlated with tests of sociability with no changes in stress related proteins such as nuclear factor kappa B (NFkB). We also found alterations in physiological responses as measured by body weight without changes in food consumption suggesting disruption of metabolism and body homeostasis.

CONCLUSIONS: We suggest that BBP administration disrupts normal learning and social behavior, and that these effects could be related to alterations of amygdala function....

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Journal Article 2013; 34(5): 395-401 PubMed PMID: 23922037 Citation  Keywords:  Aging:metabolism, Animals, Cerebral Cortex:cytology, DNA Topoisomerases, Type II:genetics, DNA-Binding Proteins:genetics, Neurons:cytology, Neuroprotective Agents:pharmacology, Sheep, Testosterone:pharmacology, Tyrosine:analogs & derivatives, Up-Regulatio.   

OBJECTIVE: This research reports the expression of topoisomerase βII in fetal sheep neuronal cells. The β isoform of DNA topoisomerase II plays a role in DNA repair process in non proliferating cells as neurons and its expression tends to be downregulated with senescence.

METHODS: Cortical neurons from 60-day-old sheep embryos underwent two protocols: the former based on rising time of culture (10, 20 and 30 days); the latter based on the 72hrs exposure to 3-nitro-L-tyrosine (oxidative/nitrosative stressor) and/or testosterone.

RESULTS: Our results showed an increase in β-galactosidase activity and, in contrast, a reduction in topoisomerase βII expression with time (first protocol). The exposure of sheep primary neurons to 3-nitro-L-tyrosine led to an upregulation of βII topoisomerase expression to be likely seen as a reaction to nitrosative stress. Testosterone addition to 3-nitro-L-tyrosine-exposed cells results in topoisomerase βII decrease possibly due to the neuroprotective properties of testosterone (second protocol). No significant variations in the marker of aging β-galactosidase were observed in the cells exposed to 3-nitro-L-tyrosine and testosterone.

CONCLUSION: The protocol based on time could be of some interest as a model of neuronal senescence in vitro. Topoisomerase βII decrease with aging likely indicates a reduced ability to repair DNA during neuronal senescence. In contrast, the second protocol may not be seen as a reliable model of aging since 3-nitro-L-tyrosine does not lead to a topoisomerase βII decrease. Testosterone was able to cope with oxidative/nitrosative damage, allowing cells to reduce their needs in DNA repair which in turn leads to a downregulation of topoisomerase IIβ expression....

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Journal Article 2013; 34(5): 359-365 PubMed PMID: 23922036 Citation  Keywords:  Animals, Apoptosis:drug effects, Caspase 3:metabolism, Cell Survival:drug effects, HSP27 Heat-Shock Proteins:metabolism, Neurons:drug effects, Neuroprotective Agents:pharmacology, PC12 Cells, Phosphorylation:drug effects, Phthalimides:pharmacology, Proto-.   

OBJECTIVE: The aim of this study was to reveal the effects of 4,5-dianilinophthalimide (DAPH), which inhibits amyloid β fibrillization, against serum deprivation (SD)-induced apoptosis and the possible mechanisms in differentiated PC12 neuron cells.

METHODS: Firstly, we evaluated whether DAPH protects cell viability exposed to SD by MTT assay. Next, we examined the changes of phospho-p38 MAPK (Thr180/Tyr182), phospho-HSP27 (Ser82), phospho-c-JUN (Ser73) and cleaved-CASP3 (Asp175) profiles by immunoblotting, in PC12 cells exposed to SD. Intracellular reactive oxygen species (ROS) level was also measured.

RESULTS: SD induced apoptosis accompanied by up-regulation of phospho-p38 MAPK (Thr180/Tyr182), phospho-HSP27 (Ser82), phospho-c-JUN (Ser73), cleaved-CASP3 (Asp175) and intracellular ROS content. Co-treatment with non-toxic doses of DAPH prevented apoptosis by the attenuation of activated proteins and reduction of ROS level. These results suggest that serum deprivation-induced apoptosis inhibited by DAPH administration.

CONCLUSION: We have provided for the first evidence that DAPH has a neuroprotective effect on SD-caused stress, probably via contributing the re-establishment of redox homeostasis....

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Journal Article 2013; 34(4): 302-308 PubMed PMID: 23803874 Citation  Keywords:  Animals, Cells, Cultured, Chromatography, Ion Exchange, Female, GABA Agents:pharmacology, Gonadotrophs:drug effects, Gonadotropin-Releasing Hormone:pharmacology, Inositol 1,4,5-Trisphosphate:biosynthesis, Luteinizing Hormone:drug effects, Pituitary Gland,.   

OBJECTIVE: Mechanism(s) responsible for VPA-induced effects on reproductive axis activity are not fully recognized. Previously we reported that VPA suppressed only GnRH-stimulated but not the basal LH release from rat anterior pituitary (AP) cells in vitro. Since the inhibitory effect of VPA was exerted only in GnRH-activated cells, potential VPA impact on GnRH-R-coupled IP3/PKC signaling could not be excluded. In this study the effect of VPA on IPs synthesis in non-stimulated and GnRH-treated rat AP cells was examined.

MATERIAL AND METHODS: In the first experiment 5 × 105 cells/ml were incubated for 3h with VPA (10 nM-10 μM), PMA (100 nM), GnRH (100 nM), PMA (100 nM) + VPA (10 nM-10 μM), GnRH (100 nM) + VPA (10 nM-10 μM). In the second experiment cells were preincubated for 24h with 1μCi myo-[23 H]-inositol, then for 30 min with 10 mM LiCl and finally for 3hr with GnRH (100 nM) VPA (1 μM, 10 μM), GnRH (100 nM) + VPA (1 μM, 10 μM). LH concentration was measured by RIA and intracellular IPs accumulation by ion-exchange chromatography analysis.

RESULTS: VPA diminished GnRH-stimulated LH release without affecting PMA-induced LH release at any dose tested. Moreover, VPA-induced increase of IPs accumulation occurred in both non-stimulated and GnRH-treated cells and intensity of cellular response was similar in both groups.

CONCLUSION: VPA affects IP3/PKC pathway activity through its up-regulatory effect on IPs synthesis in AP cells. VPA-induced inhibition of GnRH-stimulated LH release from gonadotrope cells appears to be the result of still unrecognized cellular mechanism....

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Journal Article 2013; 34(4): 282-286 PubMed PMID: 23803873 Citation  Keywords:  Causality, Chronobiology Disorders:epidemiology, Epidemiologic Methods, Humans, Neoplasms:epidemiology, Work Schedule Tolerance:physiology,.   

: With their 2007 classification - shift work involving "circadian disruption" is probably carcinogenic to humans (Group 2A) - the International Agency for Research on Cancer [IARC] provided a riddle for scientists and the public alike. Thereafter, eighteen epidemiological investigations into shift work and a host of malignant endpoints (including cancers of the breast, prostate, lung, colon, rectum, pancreas, bladder, skin and non-Hodgkin lymphoma [NHL]) as well as mortality were published. Although IARC experts identified "circadian disruption" as the critical link in the "probable" chains of cancer causation, almost none of the post-IARC studies specifically considered a disturbed temporal organization of biology. This implies that epidemiological research to-date is less focused than it should be. To illustrate a potential chronobiological fallacy of past studies, we offer a thought experiment. In addition, we consider first empirical evidence from recent research which avoided such bias. Methodological perspectives for future chronobiology-driven epidemiological research are outlined....

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Journal Article 2013; 34(4): 265-272 PubMed PMID: 23803872 Citation  Keywords:  Bipolar Disorder:psychology, Expressed Emotion, Humans, Prejudice, Self Concept, Social Stigma, Stereotyping,.   

BACKGROUND: Prejudicial beliefs, emotions, and behaviours cause discrimination against people labeled as mentally ill. This stigmatization is sometimes internalized by the patients, leading to self-stigmatization. Specific features and impacts of stigmatization and self-stigmatization in patients with bipolar illness are the subjects of this review.

METHOD: Studies were identified through PUBMED, Web of Science and Scopus databases as well as existing reviews. The search terms included "bipolar disorder", "stigma", "self-stigma" psychoeducation", "psychotherapy", "psychosocial treatment". Key articles listed in reference lists were searched.

RESULTS: Considerable recent evidence indicates that bipolar patients and their families are stigmatized, and that this stigmatization affects their quality of life as well as social functioning. The severity of stigmatization in bipolar disorder is greater than that in people with depression. There is also evidence of self-stigmatization which further decreases the quality of life. Stigmatization and self-stigmatization were shown to be one of the barriers that delay or prevent effective treatment, and thus exert adverse effects on the outcomes of bipolar disorder.

CONCLUSION: Stigma affects the experience of illness as well as social functioning in patients with bipolar disorder. The impact of stigma on the lives and treatment outcomes of patients with bipolar disorder mandates intensive effort of mental health research and policy to address this problem. Much has been done against the stigmatization of the mentally ill. But the fight against stigma remains a fundamental objective of health programs for mental health....

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Journal Article 2013; 34(4): 287-293 PubMed PMID: 23803871 Citation  Keywords:  Adult, Antidepressive Agents:therapeutic use, Cross-Over Studies, Depressive Disorder, Major:drug therapy, Double-Blind Method, Female, Hallucinogens:therapeutic use, Humans, Infusions, Intravenous, Ketamine:therapeutic use, Male, Middle Aged, Receptors, .   

OBJECTIVES: Ketamine and other NMDA (N-methyl-D-aspartate) antagonists produce fast-acting antidepressant-like effects, although the underlying mechanism is unclear. Furthermore, high affinity NMDA antagonists such as ketamine are associated with psychotomimetic effects. To date the link between the antidepressant and psychotomimetic effects of ketamine has not been explored. We examined the relationship between the antidepressant and psychotomimetic effects of a single ketamine infusion in subjects diagnosed with major depressive disorder.

METHODS: In a double-blind, cross-over, placebo-controlled, two weeks clinical trial we studied the effects of ketamine (0.54 mg/kg within 30 min) in a group of 27 hospitalized depressive patients.

RESULTS: Higher intensity of psychotomimetic symptoms, measured using BPRS, during ketamine administration correlated with alleviation in mood ratings during the following week with maximum on day seven. Ketamine was superior to placebo in all visits (day 1, 4, and 7) assessed by MADRS with effect size (Cohen´s d) of 0.62, 0.57, and 0.44 respectively. There was no significant correlation between ketamine and nor-ketamine plasma levels and MADRS score change at any study time point.

CONCLUSION: The substantial relationship between ketamine's antidepressant and psychotomimetic effects was found. This relationship could be mediated by the initial steps of ketamine's action, trough NMDA receptors, shared by both ketamine's clinical effects....

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