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Comparative Study 2010; 31(3): 336-342 PubMed PMID: 20588251 Citation  Keywords:  Animals, Antidepressive Agents:pharmacology, Antipsychotic Agents:pharmacology, Benzodiazepines:pharmacology, Cerebral Cortex:drug effects, Citrate (si)-Synthase:metabolism, Electron Transport:drug effects, Electron Transport Complex I:metabolism, Electro.   

OBJECTIVE: Mitochondrial dysfunctions, impaired bioenergetics and dysfunction of neurotrophins are included in many neurodegenerative and psychiatric diseases. We investigated in vitro effects of pharmacologically different antidepressants and mood stabilizers on mitochondrial enzymes to discover, which mitochondrial functions could be involved in pathophysiology of mood disorders.

METHODS: In vitro effects of eight pharmacologically different antidepressants (desipramine, amitriptyline, imipramine, citalopram, venlafaxine, mirtazapine, tianeptine, and moclobemide) and three mood stabilizers (lithium, valproate, and olanzapine) on the activities of mitochondrial enzymes (citrate synthase and enzymes in electron transport chain, i.e. complexes I, II, IV) were measured in crude mitochondrial fraction isolated from pig brain.

RESULTS: Most of the antidepressants and mood stabilizers inhibited the activities of respiratory electron transport chain complexes, complexes I and IV were the most affected. Statistically significant decrease of the complex I activity was caused by desipramine, amitriptyline, imipramine, citalopram, mirtazapine, valproate and olanzapine. Complex II was significantly inhibited only by amitriptyline, imipramine, citalopram and venlafaxine. Complex IV was significantly inhibited by all tested drugs except for citalopram and moclobemide. Unchanged or slightly increased citrate synthase activity was observed; significant activation of the enzyme was observed after citalopram, tianeptine and olanzapine.

CONCLUSIONS: Our results indicate that antidepressants may act generally as inhibitors of complex I and complex IV of the electron transport chain. These mitochondrial enzymes are suggested as proper candidates in searching of new biological markers of mood disorders, targets of new antidepressants or predictors of response to pharmacotherapy....

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Journal Article 2010; 31(3): 313-318 PubMed PMID: 20588243 Citation  Keywords:  Animals, Antioxidants:pharmacology, Blood Glucose:drug effects, Body Weight:drug effects, Carbolines:pharmacology, Diabetes Mellitus, Experimental:drug therapy, Glycosylation End Products, Advanced:metabolism, Kidney:drug effects, Male, Oxidative Stress:d.   

OBJECTIVES: Recent basic research and clinical data have provided new insights into the role of glycoxidative and nitrosative stresses (both oxidative stress) in diabetic complications, such as diabetic nephropathy, suggesting a different and innovative approach to antioxidant therapy. In streptozotocin-induced diabetic rat kidney, the present study investigated the effects of the synthetic pyridoindole antioxidant stobadine (STB) on renal total antioxidant potential (AOP) and protein oxidation parameters such as protein carbonyl content (PCC), advanced oxidation protein products (AOPPs) and nitrotyrosine (NT), a marker specific for protein modification by peroxynitrite.

MATERIALS AND METHODS: Wistar Albino rats were divided into two groups: normal and streptozotocin-induced diabetic rats. Each group of the animals was further divided into two groups: untreated and treated with stobadine (24.7 mg/kg) during 16 weeks daily by oral gavage.

RESULTS: The renal tissue AOP and the levels of AOPPs, PCC and NT were increased in diabetic rats compared with the untreated control animals. Furthermore, stobadine treatment significantly decreased protein carbonylation and AOPPs but not NT.

CONCLUSIONS: These findings indicate that STB is an antioxidant factor which can improve glycoxidative stress markers in kidney, while it has no effect on protein nitrosylation....

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Journal Article 2010; 31(3): 418-422 PubMed PMID: 20588242 Citation  Keywords:  Adrenal Gland Neoplasms:complications, Adult, Aged, Aged, 80 and over, Body Mass Index, Dehydroepiandrosterone Sulfate:blood, Female, Humans, Hydrocortisone:blood, Incidental Findings, Metanephrine:urine, Middle Aged, Normetanephrine:urine, Obesity:compli.   

OBJECTIVE: The influence of obesity on cancer development has been proven for numerous tumours. In contrast, the association between obesity and non-secreting adrenal incidentaloma has never been proven. Therefore, the aim of this study was to investigate this relationship in a large sample of patients.

METHODS: 143 patients with benign non-secreting adrenal incidentalomas treated in the Department of Endocrinology at the Poznan University of Medical Sciences between the years 2000-2007 were examined. To rule out subclinical hyperfunctioning lesions, serum dehydroepiandrosterone sulphate, cortisol (8 am, 6 pm, and after 1 mg dexamethasone suppression), sodium and potassium, along with concentrations of sodium, potassium, vanillylmandelic acid, metanephrine and normetanephrine in 24-hour urine collection were determined. Radiological evaluation included computed tomography and/or magnetic resonance imaging. Only non-secreting lesions and those of benign radiologic appearance were considered. The patients body mass index was compared to that of the general population of Poland and the Western Poland Region of Wielkopolska.

RESULTS: The average body mass index of our patients was 28.77 kg/m2 (SD=4.71), with a 40% prevalence of obesity in the study group. One-proportion z-test showed a statistically significantly higher prevalence of obesity as compared to the general population of Poland and Wielkopolska (40% vs 12.5%, p<0.005); the results were similar for the whole cohort, and for each gender separately.

CONCLUSIONS: This clinical research study demonstrates a strong association between obesity and incidentally discovered non-functioning adrenal tumours....

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Journal Article 2010; 31(3): 348-352 PubMed PMID: 20588238 Citation  Keywords:  Action Potentials:drug effects, Animals, Antioxidants:therapeutic use, Brain Ischemia:prevention & control, Female, Hippocampus:drug effects, In Vitro Techniques, Indoles:therapeutic use, Lactation, Pregnancy, Pregnancy Complications, Cardiovascular:drug .   

OBJECTIVE: Damage to the developing brain may be caused by maternal environment, nutritional deficiencies, failure of protective mechanisms, etc. Further, the developing brain may be damaged by intrauterine ischemia or by ischemia in newborns complicated by perinatal asphyxia. There is an effort to find agents with neuroprotective effect on the developing brain. The aim was to study the effect of the new pyridoindole antioxidant SMe1EC2 on the resistance of offspring hippocampus exposed to ischemia in vitro after treatment of mothers.

MATERIALS AND METHODS: The electrically evoked responses were determined by extracellular recording from offspring hippocampal slices. The effect of oral treatment of rats with SMe1EC2 over 18 consecutive days, from day 15 of gestation to day 10 post partum (PP) was analyzed in the model of ischemia in vitro measured on the hippocampus of 21-day-old pups, with focus on neuronal function recovery in reoxygenation.

RESULTS: Increased recovery of neuronal response was found at the end of 20-min reoxygenation in offspring hippocampal slices exposed to 10-min hypoxia/hypoglycemia from rats whose mothers were treated with the dose of 50 and 250 mg/kg of SMe1EC2, compared to control offspring slices (mothers received vehicle over the same time).

CONCLUSIONS: The increased offspring hippocampus resistance to hypoxia/hypoglycemia due to 18-day maternal treatment with SMe1EC2 might have been obtained via the transplacental way as well as in the neonatal period via breast milk, skin and saliva. The manifested neuroprotective effect of SMe1EC2 on the developing brain might find exploitation during risk pregnancy and delivery....

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Comparative Study 2010; 31(3): 363-369 PubMed PMID: 20588237 Citation  Keywords:  Animals, Antioxidants:pharmacology, Bromates:adverse effects, Dose-Response Relationship, Drug, In Vitro Techniques, Indoles:pharmacology, Kidney:drug effects, Lipid Peroxidation:drug effects, Liver:drug effects, Lung:drug effects, Melatonin:pharmacology,.   

OBJECTIVE: Potassium bromate (KBrO3) is a prooxidant and carcinogen. Melatonin is a highly effective antioxidant. Indole-3-propionic acid (IPA; indole substance) and propylothiouracil (PTU; antithyroid drug) reveal some antioxidative effects. The aim of the study was to evaluate KBrO3-induced lipid peroxidation (LPO) in vitro in tissues collected from control or melatonin-treated rats, and to compare potential preventive effects of melatonin, IPA and PTU.

MATERIALS AND METHODS: Kidney, liver and lung homogenates from either control or melatonin-pretreated rats (0.0645 mmol/kg b.w., i.p., twice daily, 10 days) were incubated in the presence of KBrO3 (0.1, 0.5, 1.0, 2.5, 5.0, 10.0 mM). Then, control lung homogenates were incubated with KBrO3 (10.0 mM) together with melatonin (0.01, 0.1, 0.5, 1.0, 5.0, 7.5 mM), or with IPA or with PTU. LPO products (malondialdehyde+4-hydroxyalkenals) were measured spectrophotometrically.

RESULTS: Melatonin injections prevented KBrO3-induced LPO in lung homogenates. Melatonin, IPA and PTU, used in vitro, reduced KBrO3-induced LPO in control lungs. Unexpectedly, KBrO3 caused a concentration-dependent decrease in LPO in liver and kidney homogenates from control but not from melatonin-treated rats.

CONCLUSIONS: Potassium bromate-induced LPO in the rat lung homogenates suggests that the lung may be the target for this carcinogen. An exposure of organisms to melatonin decreases tissue sensitivity to KBrO3-induced damage, possibly by restoring the oxidative balance....

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Journal Article 2010; 31(3): 319-324 PubMed PMID: 20588236 Citation  Keywords:  Adult, Antioxidants:metabolism, Circadian Rhythm, Female, Fetal Blood:metabolism, Gestational Age, Humans, Hydroxyl Radical:blood, Infant, Newborn, Male, Oxidative Stress:physiology, Parturition:blood, Placenta:physiology, Pregnancy,.   

BACKGROUND: Reactive oxygen species (ROS) may cause peroxydation of lipids, proteins and deoxyribonucleic acids with subsequent cell damage. The hydroxyl radical (OH*) represents a measure of global oxidative stress. Hydroxyl radicals are short-lived; they form an important part of radical chemistry nonetheless. The measure of total antioxidant system (TAS) can give useful information about the extent of defence capable of counteracting the oxidative damage. Pregnancy is an important condition that favors oxidative stress in the fetus. Clinical studies indicate a protective mechanism against O2 toxicity in the human feto-placental unit.

AIM: This study reports the OH* and TAS concentrations in mother and fetus at birth to evaluate the role of the placenta against fetal oxidative stress.

METHODS: Blood samples were collected at delivery from 45 healthy women at term and from their newborns. The maternal and neonatal OH* and TAS concentrations were compared by paired Student t-test.

RESULTS: OH* was higher in maternal blood than in cord blood (573.75+/- 170.0 UCarr/l vs 40.08+/-33.37 UCarr/l) (p<0.01); TAS concentrations did not differ between the two groups (1.11+/-0.09 mmol/l vs 1.17+/-0.12 mmol/l). Multiple regression analyses: maternal and neonatal OH* decreases with maternal age; only maternal TAS and OH* are related to gestational age in a nonlinear fashion. Female infants showed higher values of maternal and neonatal TAS as compared to male infants.

CONCLUSION: TA protective role of the placenta against oxidative damage is in keeping with a large enough gradient of ROS (between mother and fetus) and the passage of TAS from mother to fetus....

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Journal Article 2010; 31(3): 359-362 PubMed PMID: 20588235 Citation  Keywords:  Adult, Dopamine:physiology, Female, Genetic Predisposition to Disease, Haloperidol:pharmacology, Humans, Huntingtin Protein, Huntington Disease:blood, Hypothalamo-Hypophyseal System:drug effects, Male, Middle Aged, Nerve Tissue Proteins:genetics, Nuclear .   

OBJECTIVES: In addition to neuronal loss in striatum and cerebral cortex that characterizes Huntington's disease (HD), hypothalamic atrophy has also been found only in certain areas, probably not including dopaminergic functions.

METHODS: We assessed the reactivity of the hypothalamus-pituitary dopaminergic system by measuring the acute prolactin (PRL) responses to 5 mg i.m. haloperidol in male and female HD patients and in female subjects with expanded CAG repeats in the Huntington gene before disease onset, as well as in a group of healthy males.

RESULTS: The responses of the male patients were similar to those of a group of male healthy volunteers. Females gave higher PRL responses, with no differences in the response patterns of female patients and females at risk for HD. PRL elevations were not related to severity of illness, or to presence of dementia, depression, or psychotic features.

CONCLUSIONS: The results implicate a normal dopaminergic input from hypothalamus to pituitary and preserved pituitary dopamine receptors, indicating that hypothalamic atrophy in HD does not affect mechanisms involved in PRL secretion by haloperidol....

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Case Reports 2010; 31(3): 297-300 PubMed PMID: 20588234 Citation  Keywords:  Antihypertensive Agents:therapeutic use, Child, Female, Humans, Magnetic Resonance Imaging, Nephrotic Syndrome:complications, Posterior Leukoencephalopathy Syndrome:complications,.   

OBJECTIVE: Posterior Reversible Encephalopathy Syndrome (PRES) is a rare complication of nephrotic syndrome in children. This clinical condition is caused by localized brain angioedema mostly in parieto-occipital region and results in dramatic and acute features as sudden loss of consciousness, epileptic paroxysms, strong headache or visual disturbances. Uncontrolled hypertension often participates in PRES development.

CASE: We present the case of a 5-year-old girl treated for relapse of nephrotic syndrome.

RESULTS: At the time of edema regression and weight reduction, a sudden loss of consciousness and worsening of hypertension occurred. Brain MRI demonstrated extended multifocal changes strongly suspicious of encephalitis. After exclusion of herpetic encephalitis, the clinical picture was classified as PRES. Successful antihypertensive treatment led to general improvement of the girl's health within 48 hours and resolution of MRI brain hyperintensities occurred within the next three months.

CONCLUSIONS: The aim of our case report is to us remind of possible development of PRES at the time of edema regression in nephrotic syndrome....

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