Search NEL Online

Journal Article 2014; 35(8): 746-749 PubMed PMID: 25702305 Citation  Keywords:  Adult, Case-Control Studies, Depressive Disorder, Major:metabolism, Female, Humans, Hydroxyindoleacetic Acid:metabolism, Male, Saliva:chemistry, Time Factors, Young Adult,.   

OBJECTIVES: Central serotonergic dysfunction is reported in major depressive disorder (MDD). Serotonin is primarily metabolized to 5-hydroxyindole acetic acid (5-HIAA) and its plasma, urinary or cerebrospinal fluid concentrations were extensively studied in depression. No data is available on salivary 5-HIAA (s5-HIAA) in MDD to date.

METHODS: The basal, non-stimulated s5-HIAA concentration was studied in this cross-sectional case-control study on 20 non-late-life adult, short-illness-duration first-episode, treatment-naïve MDD patients and in 20 age- and sex-matched healthy controls. Depressed patients showed a score in the Hamilton Rating Scale for Depression (HAMD-17) higher than 20.

RESULTS: No significant difference in s5-HIAA concentration between patients with MDD and controls was observed. In post hoc analysis significantly lower s5-HIAA was seen in non-melancholic MDD (p=0.026) as related to controls whereas no difference was seen between melancholic MDD patients and controls. The concentration of s5-HIAA was not significantly correlated neither with duration nor the severity of depressive symptoms as measured by the total HAMD-17 score.

CONCLUSION: No difference was observed in baseline s5-HIAA concentration between MDD patients and healthy controls. That observation corroborates with previous MDD studies on 5-HIAA concentrations in bodily fluids where unaltered 5-HIAA concentration is seen in the absence of serotonin-related behaviours including impulsivity, suicidality, and anxiety. Salivary 5-HIAA use remains to be determined....

Read abstract  Full text PDF

Journal Article 2014; 35(Suppl 2): 114-122 PubMed PMID: 25638375 Citation  Keywords:  Animals, Aryl Hydrocarbon Hydroxylases:metabolism, Cell Membrane:metabolism, Cytochrome P450 Family 2, Cytochromes b5:metabolism,.   

OBJECTIVES: The mammalian mixed function oxidase (MFO) system participates in hydroxylation of many hydrophobic endogenous compounds as well as xenobiotics such as drugs and carcinogens. This biotransformation system, located in a membrane of endoplasmic reticulum, consists of cytochrome P-450 (P450), NADPH:P450 oxidoreductase and a facultative component, cytochrome b5. The knowledge of the interactions among the individual components of the MFO system is essential to understand the relationships between the structure and function of this system that finally dictate a qualitative and quantitative pattern of produced metabolites (e.g. detoxified xenobiotics and/or activated carcinogens). To elucidate the quantitative aspects of the interactions within the MFO system we acquired the photo-initiated cross-linking approach.

METHODS: The photo-initiated cross-linking employing cytochrome b5 as a protein nanoprobe [an amino acid analogue of methionine (pMet) was incorporated into cytochrome b5 sequence during recombinant expression] was used to quantify its interaction with P450 2B4 in a functional membrane complex. The cross-linking was initiated by UV-irradiation that formed from a pMet photolabile diazirine group highly reactive carbene biradical. This biradical is able to covalently bind amino acids in the close proximity and to form cross-link. The Met 96 of cytochrome b5 is situated in a linker region between its catalytic and membrane domains, while Met 126 and 131 are located in its membrane domain. The combination of several methods (electrophoresis in polyacrylamide gel, isoelectric focusing, Edman N-terminal degradation and amino acid analysis) was employed to characterize the molar ratio of P450 2B4 to cytochrome b5 in formed covalent cross-links to quantify their transient interactions.

RESULTS: The successfully produced cytochrome b5 nanoprobe (with confirmed pMet incorporation by mass spectrometry) stimulates the catalytical activity of P450 2B4 when reconstituted with NADPH:P450 oxidoreductase in vitro in dilauroylphosphatidylcholine (DLPC) vesicles. The cross-linking was carried out in similar reconstituted system without NADPH:P450 oxidoreductase, and at least three products were separated on 1D SDS-PAGE. The molar ratio of P450 to cytochrome b5 in each complex was estimated using the above-mentioned combination of methods as 1:1, 1:2 and 2:1.

CONCLUSIONS: The results demonstrate the utility of cytochrome b5 nanoprobe to study the interactions in MFO system. Using this nanoprobe, heterodimer with P450 2B4 and in addition also heterooligomers were identified, suggesting rather complex interactions of both proteins in this system that suppose the formation of such multimeric structures in the membrane of endoplasmic reticulum.

...

Read abstract  Full text PDF

Journal Article 2014; 35(7): 586-593 PubMed PMID: 25617881 Citation  Keywords:  Aged, Aged, 80 and over, Aging:immunology, Biomarkers:cerebrospinal fluid, Cytokines:cerebrospinal fluid, Dementia:cerebrospinal fluid, Humans, Hydrocephalus, Normal Pressure:cerebrospinal fluid, Postural Balance, Urinary Incontinence:cerebrospinal fluid,.   

OBJECTIVES: Normal pressure hydrocephalus (NPH) is a treatable neurological syndrome developing in the elderly. It is characterized by balance impairment, urinary incontinence and dementia development caused by disorders in the cerebrospinal fluid (CSF) circulation. The diagnosis can be easily mistaken for other neurodegenerative diseases, which are often accompanied by inflammation and the production of cytokines. The aim of our study was to determine and compare selected CSF and plasma cytokines with respect to their informative value for laboratory diagnostics of NPH.

METHODS: The levels of IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40L and TNF-α were measured in the CSF and plasma in age-matched subjects with NPH (n=20) and controls (n=20) by multiplex assay.

RESULTS: CSF IL-1β, IL-6 and IL-10 were significantly increased on the 1st day of lumbar drainage in NPH (p<0.01). No significant changes were observed in the plasma. The CSF cytokines were one to three orders of magnitude higher compared to the plasma.

CONCLUSION: CSF can better show the neurodegenerative changes in the brain. The cytokines IL-1β, IL-6 and IL-10 may be helpful in NPH diagnostics....

Read abstract  Full text PDF

Journal Article 2014; 35(6): 454-462 PubMed PMID: 25433849 Citation  Keywords:  Acetylglucosaminidase:metabolism, Alzheimer Disease:drug therapy, Animals, Antioxidants:pharmacology, CA1 Region, Hippocampal:drug effects, Cognition Disorders:drug therapy, Disease Models, Animal, Indoles:pharmacology, Male, Malondialdehyde:metabolism, M.   

BACKGROUND: The idea of antioxidant therapy attenuating Alzheimer disease (AD) neuropathology starts to be attractive. Animal models are often used in these studies. An AD-like model of trimethyltin (TMT)-induced neurodegeneration, targeting the hippocampus, involves neuronal cell death and cognitive impairment.

OBJECTIVES: Effect of the pyridoindole SMe1EC2 (3×50 mg/kg) and vitamin C (3×50mg/kg) was analyzed in the model of TMT-induced (8 mg/kg) neurodegeneration.

METHODS: The study was focused on the effect of the antioxidants tested on learning performance in the Morris water maze (MWM) on days 21-25 after TMT administration, on biochemical variables - malondyaldehyde (MDA) and lysosomal enzyme NAGA in brain cortex and blood serum, and on pyramidal cell number in the CA1 area of the hippocampus on day 31 after TMT administration in adult male Wistar rats (n=32).

RESULTS: Critical deterioration of learning performance was observed due to the TMT administration in the MWM. Further, apparent reduction of pyramidal cell number to 21% in the CA1 area of the hippocampus, increased MDA and NAGA activity in serum and increased NAGA activity in the cortex were determined contrary to controls. In serum, an increase of MDA level was prevented by both antioxidants tested without any effect on NAGA activity. SMe1EC2 apparently preserved pyramidal cell viability in the CA1 area. Both substances tested failed to ameliorate the detrimental effect of TMT on spatial memory.

CONCLUSION: The biochemical and morphometrical findings suggest that reduction of oxidative stress may play a role in AD-like neurodegeneration. Different doses and timing of SMe1EC2 administration might bring improvement in next learning performance....

Read abstract  Full text PDF

Comparative Study 2014; 35(4): 314-321 PubMed PMID: 25038601 Citation  Keywords:  Adult, Faculty, Female, Firefighters, Humans, Hydrocortisone:biosynthesis, Male, Middle Aged, Occupational Diseases:etiology, Saliva:chemistry, Sex Factors, Stress, Psychological:metabolism,.   

BACKGROUND: It's indicated negative-perceived stress could induce worse health status and change of cortisol secretion.

OBJECTIVES: To assess salivary cortisol levels in two occupations with a high psychosocial workload, but different features, teachers and firefighters.

METHODS: The study population consisted of 142 school teachers and 136 firefighters. Four saliva samples were collected from pedagogical participants during their busiest workday. The cortisol measures used were: morning values, evening values, slope of decline, ratio (evening value divided by morning value), and area under the curve (AUC).

RESULTS: The salivary cortisol measurements in both genders were almost equal regarding morning values, slope, and AUC increase. Evening values were lower and the relative reactivity was higher (lower ratio) for female teachers, compared to male teachers. There was a tendency of a lower total daytime output of cortisol (AUC ground) among female teachers. Firefighters had lower levels of cortisol, lower total daytime output, and higher relative reactivity (lower ratio), but lower absolute reactivity, regarding both slope and AUC increase.

CONCLUSION: Overall, male teachers might be the group most affected by stress in this study, even if some of their cortisol values were almost equal to the female teachers' values. Male teachers also seemed to be more affected by stress, according to salivary cortisol, compared to male firefighters, even if there were some inconsistencies....

Read abstract  Full text PDF

Clinical Trial 2014; 35(2): 123-128 PubMed PMID: 24878976 Citation  Keywords:  Aged, Electromyography, Fatty Acids, Monounsaturated:adverse effects, Female, Fluorobenzenes:adverse effects, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors:adverse effects, Incidence, Indoles:adverse effects, Male, Middle Aged, Muscular Diseases:.   

OBJECTIVES: The goal of this clinical trial was to determine the incidence of undesirable side effects, and to ascertain any occurrence of genetic polymorphisms.

MATERIAL AND METHODS: Clinically, we looked for manifestations of a benign myositis and of serious rhabdomyolysis. We observed a group 198 patients treated with statins, primarially fluvastatin and rosuvastatin. There were 126 (mean age = 58.3 ± 4.1; male 91, mean age = 57.4 ± 5.9; female 35, mean age = 60.5 ± 6.5) patients in a subgroup where we administered rosuvastatin. Undesirable muscular signs and symptoms were present in 32 patients (25.39%). In 11 (8.73% of the total 126) CK level increased maximally to 4 times ULN, in 6 (4.7%) statins were excluded because of very intense subjective suffering. CK levels 2-5 times ULN were present in 9 (7.14%). CK blood levels over 10 times ULN or higher indicated statins exclusion in 2 (1.58%). Increased levels of the further muscular enzyme AST by 5 times ULN were present in 16 (12.69%), up to 10 times ULN in 2 (1.58%), and over 10 times ULN also in 2 (1.58%).

RESULTS: We observed rhabdomyolysis in 6 patients (3.03% of the total 198 patients group) using other types of statins (three of them undergo chronic hemodialysis). In this group we performed molecular-genetic analysis of the following proteins relating to statin myopathy: SLCO1B1(388AA/AG-521TT) - (discovered polymorphism in 1 patient), further cytochroms Cyp 2C9 (in 1 patient), 2C8 (in 1 patient), Cyp SA/4 (non discovered positivity) and finally UGT1A1*2B (discovered in 2 patients).

CONCLUSIONS: In the group of patients treated by rosuvastatin, we discovered not one case of rhabdomyolysis. In each patient with rhabdomyolysis (brown urine discoloration, mal-odorous urine, painful muscle cramps, muscle weakness, fatigue) at least one polymorphism of "statins´ genes" was present....

Read abstract  Full text PDF

Comparative Study 2014; 35(1): 20-27 PubMed PMID: 24625913 Citation  Keywords:  Adult, Antibodies:immunology, Blood Glucose:analysis, Cholesterol:blood, Cholesterol, LDL:blood, Comorbidity, Cytomegalovirus:pathogenicity, Cytomegalovirus Infections:blood, Dehydroepiandrosterone:blood, Female, Humans, Immunoglobulin G:immunology, Male,.   

OBJECTIVES: Toxoplasma gondii, the protozoan parasite infecting about 30% population worldwide, is suspected to be the etiological agent of certain form of schizophrenia disease. Toxoplasma is known to change levels of certain neurotransmitters, cytokines and several hormones in both infected animals and humans. A common feature of toxoplasmosis and schizophrenia is a disorder of immune system.

METHODS: Here we studied the levels of five neuro- and immunomodulatory steroids, selected hormones and lipids in sera of 173 schizophrenia patients.

RESULTS: Toxoplasma infected schizophrenia patients expressed only insignificantly lower concentration of neuro- and immunomodulatory DHEA metabolites. Infected women had higher concentration of glucose while infected men had higher concentration of cholesterol and LDL cholesterol. No significant effect of human cytomegalovirus infection on the concentration of the above parameters was observed. The difference in the concentration of DHEA metabolites faded with the decrease of the concentration of anti-Toxoplasma IgG antibodies (i.e. with the duration of Toxoplasma infection) while the difference in the concentration of cholesterol and LDL-cholesterol increased with the decrease of the concentration of anti-Toxoplasma IgG antibodies. The prevalence of toxoplasmosis in male (53.2%) but not female (29.8%) schizophrenia patients was unusually high in comparison with prevalence of toxoplasmosis in a general population.

CONCLUSION: Our results provided an explanation for seemingly decreasing prevalence of toxoplasmosis in schizophrenia patients observed in current studies (increased concerns about the rights of patients resulting in absence of non-cooperative Toxoplasma-positive patients in the study population) and suggest possible explanation for reported positive correlation between prevalence of toxoplasmosis and incidence of cardiovascular diseases (accelerated atherosclerotic development due to increased level of cholesterol and LDL in Toxoplasma infected humans)....

Read abstract  Full text PDF

Journal Article 2014; 35(1): 58-63 PubMed PMID: 24625912 Citation  Keywords:  Adult, Anxiety:etiology, Biomarkers:blood, Blood-Brain Barrier:metabolism, Cell Membrane Permeability:physiology, Depression:etiology, Humans, Hydrocortisone:blood, Inflammation:etiology, Interleukin-6:blood, Male, Military Personnel, Rest:physiology, S10.   

BACKGROUND: Experimental data suggest stress-related cognitive dysfunction may be associated with increased blood-brain-barrier (BBB) permeability secondary to immune activation.

METHODS: We investigated the relationship between prolonged and intense physical and psychological combat-training stress, immune activation and blood-brain-barrier permeability in 37 healthy male army medical rapid response troops.

RESULTS: Soldiers during intense combat training showed greater self-reported stress, anxiety and depression levels than at rest, as assessed by specific questionnaires. S100B, a marker of BBB permeability, as well as serum cortisol, IL-6 and TNF-α concentrations, were significantly increased in soldiers during combat training compared to rest (all p<0.05). Serum S100B correlated negatively with morning serum cortisol in soldiers during combat training, but not during the rest period (r=-0.387, p<0.05).

CONCLUSION: We conclude that combat training inducing significant levels of stress, depression and anxiety is accompanied by evidence of increased blood-brain barrier permeability and by increases in systemic pro-inflammatory mediators....

Read abstract  Full text PDF