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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.r />r /> 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.r />r /> 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.r />r /> 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.r />r /> 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.r />r /> 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.r />r /> 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.r />r /> 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.r />r /> 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.r />r /> 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.r />r /> 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.r />r /> 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.r />r /> 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.r />r /> 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.r />r /> 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.r />r /> 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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Case Reports 2013; 34(4): 273-274 PubMed PMID: 23803870 Citation  Keywords:  Diagnosis, Differential, Female, Humans, Middle Aged, Neoplasm Recurrence, Local:diagnostic imaging, Neuroendocrine Tumors:diagnostic imaging, Organometallic Compounds, Pancreatic Neoplasms:diagnostic imaging, Positron-Emission Tomography, Radiopharmaceut.   

: 56-year old woman was operated of a pancreatic NET in May 2011. Abdominal pain had led to imaging and consecutively the finding of cholecystolithiasis and the tumor. The gall bladder, left hemi-pancreas, regional lymph nodes and the (unintentional injured) spleen were resected. At routine control examination in October 2012 CT presented three contract enhancing intra-abdominal lesions with a diameter of 2-3.5 cm. Consecutively 68Ga-DOTA-NOC PET-CT showed high tracer uptake (SUV 10-12) at these lesions. Therefore a relapse of the neuro-endocrine tumor was suspected. After reoperation in December 2012 histology did not reveal any sign of neuroendocrine tumor but identified spleen tissue most probably caused by splenosis accidentally seeded at the first operation. Physiologically the spleen is highly avid at 68Ga-DOTATOC PET, but splenosis presents with less standard uptake value. In our case the described lesions presented with an SUV quite comparable to that of neuroendocrine tumor tissue....

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Journal Article 2013; 34(4): 309-313 PubMed PMID: 23803869 Citation  Keywords:  Electrophoresis, Polyacrylamide Gel:instrumentation, Female, Humans, Hyperlipoproteinemias:diagnosis, Lipoprotein(a):analysis, Lipoproteins:analysis, Male, Middle Aged, Nephelometry and Turbidimetry,.   

OBJECTIVE: Identification of lipoprotein subfractions in lipoprotein profile by Lipoprint LDL system, where a lipoprotein(a), an independent risk factor for the development of cardiovascular disease, migrates with. The concentration of lipoprotein(a) in serum over 0.3 g/l increases the risk of athero-thrombosis and a brain stroke. The persons with increased levels of lipoprotein(a) and contemporarily increased cholesterol level in serum, are at increased risk of the inception of cardiovascular or cerebrovascular event even 3-times.r />r /> PATIENTS AND METHODS: In a general group of subjects with increased serum concentration of lipoprotein(a) a lipoprotein profile analysis was performed. The general group of subjects was divided into two groups: subgroup with the lipoprotein(a) concentration in the range between 0.3-0.8 g/l and a subgroup with the lipoprotein(a) concentration over 0.8 g/l, to learn if the lipoprotein(a) particles of different serum concentration and different size do not migrate in different positions of the lipoprotein spectrum. For the analysis of serum lipoproteins an innovated electrophoresis method on polyacrylamide gel (PAG) - Lipoprint LDL system USA, was used. Lipids: a total cholesterol and triglycerides in serum were analysed by an enzymatic method CHOD PAP (Roche Diagnostics, FRG), lipoprotein(a) was analysed by an immuno-nephelometric method (Roche Diagnostics, FRG).r />r /> RESULTS: In the Lipoprint LDL system using a polyacrylamide gel (PAG) for the lipoprotein separation, lipoprotein(a) migrates in the position IDL2-IDL3. In the band of IDL2 a high Lp(a) values can be identified, when the increment of IDL2 subfraction is over the value of 0.015 g/l, i.e. 15 mg/dl (reference range for IDL2) and when the increment of IDL3 subfraction is over the value of 25 mg/dl, i.e. 0.025 g/l (reference range for IDL3).r />r /> CONCLUSIONS: A clear contribution of new method is: identification of the lipoprotein subpopulations where the lipoprotein(a) migrates with different migration position for the mild increased lipoprotein(a) concentration and high lipoprotein(a) concentration in serum was not confirmed....

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