Clinical Indicators of Bone Deterioration in Alcoholic Liver Cirrhosis and Chronic Alcohol Abuse: Looking beyond Bone Fracture Occurrence.

Although previous studies indicated that chronic alcohol abuse (CAA) and alcoholic liver cirrhosis (ALC) are associated with increased bone fragility, understanding bone fragility determinants is still modest in these individuals. We used a comprehensive individualized clinical fracture risk assessment approach (vertebral osteodensitometry, femoral osteodensitometry and geometry, and serum bone turnover biomarkers) to compare adult male patients with ALC who have not previously had femoral or vertebral fractures (n = 39), patients with CAA (without liver cirrhosis, n = 78) who have not previously had femoral or vertebral fractures and healthy age- and sex-matched controls (n = 43). Our data suggested that intertrochanteric bone mineral density was significantly lower in ALC and CAA patients than in controls. Also, the trabecular bone score was considerably lower in ALC patients compared with CAA and control individuals. The most significant inter-group differences in femoral geometry were noted on the femoral shaft. Patients with ALC and CAA have a higher 10-year risk of major osteoporotic fractures compared to the controls. Analysis of bone turnover biomarkers showed increased osteoprotegerin and beta-C-terminal telopeptide serum concentrations and decreased insulin growth factor-1 concentrations in patients with ALC compared to CAA and control groups. Our data revealed that bone alterations are present in patients with ALC and CAA even if they did not sustain a nontraumatic bone fracture, but it is also indicative that current bone-assessing clinical methods are not entirely reliable. Thus, future studies should focus on developing a reliable integrative clinical tool that can be used to accurately predict and prevent bone fracture occurrences in patients with ALC and CAA.

Decreased Plasma Levels of Kynurenine and Kynurenic Acid in Previously Treated and First-Episode Antipsychotic-Naive Schizophrenia Patients.

Tryptophan (TRP) catabolites exert neuroactive effects, with the plethora of evidence suggesting that kynurenic acid (KYNA), a catabolite of the kynurenine pathway (KP), acts as the regulator of glutamate and acetylcholine in the brain, contributing to the schizophrenia pathophysiology. Newer evidence regarding measures of KP metabolites in the blood of schizophrenia patients and from the central nervous system suggest that blood levels of these metabolites by no means could reflect pathological changes of TRP degradation in the brain. The aim of this study was to investigate plasma concentrations of TRP, kynurenine (KYN) and KYNA at the acute phase and remission of schizophrenia in a prospective, case-control study of highly selected and matched schizophrenia patients and healthy individuals. Our study revealed significantly decreased KYN and KYNA in schizophrenia patients (p < 0.001), irrespective of illness state, type of antipsychotic treatment, number of episodes or illness duration and no differences in the KYN/TRP ratio between schizophrenia patients and healthy individuals. These findings could be interpreted as indices that kynurenine pathway might not be dysregulated in the periphery and that other factors contribute to observed disturbances in concentrations, but as our study had certain limitations, we cannot draw definite conclusions. Further studies, especially those exploring other body compartments that participate in kynurenine pathway, are needed.

Effects of Maternal Deprivation on the Prefrontal Cortex of Male Rats: Cellular, Neurochemical, and Behavioral Outcomes.

Stressful events experienced during early life are associated with increased vulnerability of developing psychopathology in adulthood. In the present study, we exposed 9-day-old Wistar rats to 24 h maternal deprivation (MD) with the aim to investigate the impact of early life stress (ELS) on morphological, biochemical, and functional aspects of the prefrontal cortex (PFC), a brain region particularly sensitive to stress. We found that in the superficial medial orbital cortex (MO), young adult male rats had reduced density of GAD67 and CCK immunopositive cells, while the rostral part of the ventral lateral orbital cortex (roVLO) showed a decrease in the density of GAD67 immunopositive cells in both superficial and deep layers. In addition, the superficial rostral part of area 1 of the cingulate cortex (roCg1) and deep prelimbic cortex (PrL) was also affected by MD indicated by the reduction in PV immunopositive cellular density. Furthermore, MD induced upregulation of brain-derived neurotrophic factor (BDNF), while it did not affect the overall expression of Iba1 in neonatal or young adult PFC as measured by Western blot, however, microglial activation in young adult MD rats was detected immunohistochemically in deep layers of MO and infralimbic cortex (IL). Interestingly, when young adult male rats were subjected to a behavioral flexibility test in a T-maze, MD rats showed a subtle impairment in T-maze reversal learning indicating a mildly affected PFC function. Taken together, our findings demonstrated that MD reduced the density of interneurons and induced microglial activation, in particular, PFC areas at young adulthood, and could alter synaptic plasticity accompanied by PFC dysfunction.

Effects of Vitamin D3 on the NADPH Oxidase and Matrix Metalloproteinase 9 in an Animal Model of Global Cerebral Ischemia.

Decreased blood flow in the brain leads to a rapid increase in reactive oxygen species (ROS). NADPH oxidase (NOX) is an enzyme family that has the physiological function to produce ROS. NOX2 and NOX4 overexpression is associated with aggravated ischemic injury, while NOX2/4-deficient mice had reduced stroke size. Dysregulation of matrix metalloproteinases (MMPs) contributes to tissue damage. The active form of vitamin D3 expresses neuroprotective, immunomodulatory, and anti-inflammatory effects in the CNS. The present study examines the effects of the vitamin D3 pretreatment on the oxidative stress parameters and the expression of NOX subunits, MMP9, microglial marker Iba1, and vitamin D receptor (VDR), in the cortex and hippocampus of Mongolian gerbils subjected to ten minutes of global cerebral ischemia, followed by 24 hours of reperfusion. The ischemia/reperfusion procedure has induced oxidative stress, changes in the expression of NOX2 subunits and MMP9 in the brain, and increased MMP9 activity in the serum of experimental animals. Pretreatment with vitamin D3 was especially effective on NOX2 subunits, MMP9, and the level of malondialdehyde and superoxide anion. These results outline the significance of the NOX and MMP9 investigation in brain ischemia and the importance of adequate vitamin D supplementation in ameliorating the injury caused by I/R.

The influence of ageing on the extrapineal melatonin synthetic pathway.

Ageing affects various physiological and metabolic processes in a body and a progressive accumulation of oxidative damage stands out as often used explanation. One of the most powerful scavenger of reactive oxygen species (ROS) in all organs is melatonin. A majority of melatonin supplied to the body via blood originates from the pineal gland. However, we have been interested in a locally produced melatonin. We have used 2.5- and 36-months-old Wistar rats. Tissues were collected and gene expression of AA-NAT and ASMT, the two key enzymes in a synthesis of melatonin, was determined in brain, liver, kidney, heart, skin, and intestine. Since melatonin can influence antioxidant enzymes, the activity of superoxide dismutase (SOD) and catalase (CAT), and the level of GSH were measured in liver. In addition, Copper (Cu), Zinc (Zn), and Manganese (Mn) were also determined in liver since these microelements might affect the activity of antioxidant enzymes. The expression of AA-NAT and ASMT was increased in liver and skin of old animals. A positive correlation in AA-NAT and ASMT expression was observed in liver, intestine and kidney. Moreover, the activity of CAT enzyme in liver was increased while SOD activity was decreased. SOD and CAT were probably affected by the observed decreased amount of Cu, Zn, and Mn in liver of old animals. In our model, extrapineal melatonin pathway in ageing consisted of complex interplay of locally produced melatonin, activities of SOD and CAT, and adequate presence of Cu, Zn and Mn microelements in order to defend organs against oxidative damage.

NADPH oxidase and redox status in amygdala, hippocampus and cortex of male Wistar rats in an animal model of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a highly prevalent and impairing disorder. Oxidative stress is implicated in its pathogenesis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of free radicals. The aim of the study was to assess oxidative stress parameters, activities of respiratory chain enzymes, and the expression of NADPH oxidase subunits (gp91phox, p22phox, and p67phox) in the single prolonged stress (SPS) animal model of PTSD. Twenty-four (12 controls; 12 subjected to SPS), 9-week-old, male Wistar rats were used. SPS included physical restraint, forced swimming, and ether exposure. The rats were euthanized seven days later. Cortex, hippocampus, amygdala, and thalamus were dissected. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), Complex I, and cytochrome C oxidase were measured using spectrophotometric methods, while the expression of NADPH oxidase subunits was determined by Western blot. Increased MDA and decreased GSH concentrations were found in the amygdala and hippocampus of the SPS rats. SOD activity was decreased in amygdala and GPx was decreased in hippocampus. Increased expression of the NADPH oxidase subunits was seen in amygdala, while mitochondrial respiratory chain enzyme expression was unchanged both in amygdala and hippocampus. In the cortex concentrations of MDA and GSH were unchanged despite increased Complex I and decreased GPx, while in the thalamus no change of any parameter was noticed. We conclude that oxidative stress is present in hippocampus and amygdala seven days after the SPS procedure. NADPH oxidase seems to be a main source of free radicals in the amygdala.

Haloperidol affects bones while clozapine alters metabolic parameters - sex specific effects in rats perinatally treated with phencyclidine.

BACKGROUND: The presentation of schizophrenia (SCH) symptoms differs between the sexes. Long-term treatment with antipsychotics is frequently associated with decreased bone mineral density, increased fracture risk and metabolic side effects. Perinatal phencyclidine (PCP) administration to rodents represents an animal model of SCH. The aim of this study was to assess the effects of chronic haloperidol and clozapine treatment on bone mass, body composition, corticosterone, IL-6 and TNF-α concentrations and metabolic parameters in male and female rats perinatally treated with PCP. METHODS: Six groups of male and six groups of female rats (n = 6-12 per group) were subcutaneously treated on 2nd, 6th, 9th and 12th postnatal day (PN), with either PCP (10 mg/kg) or saline. At PN35, one NaCl and PCP group (NaCl-H and PCP-H) started receiving haloperidol (1 mg/kg/day) and one NaCl and PCP group (NaCl-C and PCP-C) started receiving clozapine (20 mg/kg/day) dissolved in drinking water. The remaining NaCl and PCP groups received water. Dual X-ray absorptiometry measurements were performed on PN60 and PN98. Animals were sacrificed on PN100. Femur was analysed by light microscopy. Concentrations of corticosterone, TNF-α and IL-6 were measured in serum samples using enzyme-linked immunosorbent assay (ELISA) commercially available kits. Glucose, cholesterol and triacylglycerol concentrations were measured in serum spectrophotometrically. RESULTS: Our results showed that perinatal PCP administration causes a significant decrease in bone mass and deterioration in bone quality in male and female rats. Haloperidol had deleterious, while clozapine had protective effect on bones. The effects of haloperidol on bones were more pronounced in male rats. It seems that the observed changes are not the consequence of the alterations of corticosterone, IL-6 and TNF-α concentration since no change of these factors was observed. Clozapine induced increase of body weight and retroperitoneal fat in male rats regardless of perinatal treatment. Furthermore, clozapine treatment caused sex specific increase in pro-inflammatory cytokines. CONCLUSION: Taken together our findings confirm that antipsychotics have complex influence on bone and metabolism. Evaluation of potential markers for individual risk of antipsychotics induced adverse effects could be valuable for improvement of therapy of this life-long lasting disease.

Long-Term Effects of Maternal Deprivation on Redox Regulation in Rat Brain: Involvement of NADPH Oxidase.

Maternal deprivation (MD) causes perinatal stress, with subsequent behavioral changes which resemble the symptoms of schizophrenia. The NADPH oxidase is one of the major generators of reactive oxygen species, known to play a role in stress response in different tissues. The aim of this study was to elucidate the long-term effects of MD on the expression of NADPH oxidase subunits (gp91phox, p22phox, p67phox, p47phox, and p40phox). Activities of cytochrome C oxidase and respiratory chain Complex I, as well as the oxidative stress parameters using appropriate spectrophotometric techniques were analyzed. Nine-day-old Wistar rats were exposed to a 24 h maternal deprivation and sacrificed at young adult age. The structures affected by perinatal stress, cortex, hippocampus, thalamus, and caudate nuclei were investigated. The most prominent findings were increased expressions of gp91phox in the cortex and hippocampus, increased expression of p22phox and p40phox, and decreased expression of gp91phox, p22phox, and p47phox in the caudate nuclei. Complex I activity was increased in all structures except cortex. Content of reduced glutathione was decreased in all sections while region-specific changes of other oxidative stress parameters were found. Our results indicate the presence of long-term redox alterations in MD rats.

Anxiety-related behavior in hyperhomocysteinemia induced by methionine nutritional overload in rats: role of the brain oxidative stress.

The aim of this study was to examine the effects of a methionine-enriched diet on anxiety-related behavior in rats and to determine the role of the brain oxidative status in these alterations. Adult male Wistar rats were fed from the 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing with standard diet: 7.7 g/kg). Rats were tested in open field and light-dark tests and afterwards oxidative status in the different brain regions were determined. Hyperhomocysteinemia induced by methionine-enriched diet in this study decreased the number of rearings, as well as the time that these animals spent in the center of the open field, but increased index of thigmotaxy. Oxidative status was selectively altered in the examined regions. Lipid peroxidation was significantly increased in the cortex and nc. caudatus of rats developing hyperhomocysteinemia, but unaltered in the hippocampus and thalamus. Based on the results of this research, it could be concluded that hyperhomocysteinemia induced by methionine nutritional overload increased anxiety-related behavior in rats. These proanxiogenic effects could be, at least in part, a consequence of oxidative stress in the rat brain.

Effects of IL-33/ST2 pathway in acute inflammation on tissue damage, antioxidative parameters, magnesium concentration and cytokines profile.

AIM: The aim of this study was to examine the role of IL-33/ST2 pathway in a pathogenesis of acute inflammation and its effects on tissue damage, antioxidative capacity, magnesium concentration and cytokine profile in acutely inflamed tissue. MATERIAL AND METHODS: Male mice were randomly divided in four groups: wild-type control group (WT-C), ST2 knockout control group (KO-C), wild-type inflammatory group (WT-I), and ST2 knockout inflammatory group (KO-I). Acute inflammation was induced in WT-I and KO-I by intramuscular injection of turpentine oil, while mice in WT-C and KO-C were treated with saline. After 12h, animals were euthanized, and blood was collected for determination of creatine kinase (CK) and aspartate transaminase (AST) activity. The treated tissue was used for histopathological analysis, determination of volume density of inflammatory infiltrate (Vdii) and necrotic fiber (Vdnf), gene expression of interleukin (IL)-33, ST2, tumor necrosis factor alpha (TNF-alpha), IL-6, IL-12p35, and transforming growth factor beta (TGF-beta), concentration of magnesium (Mg), copper (Cu), selenium (Se), manganese (Mn) and reduced glutathione (GSH), and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. RESULTS: Presence of inflammatory infiltration and necrosis in the treated tissue was histopathologically confirmed in WT-I and KO-I. Vdii was significantly higher in WT-I when compared to KO-I, whereas Vdnf did not significantly differ between WT-I and KO-I. CK and AST significantly increased in both inflammatory groups when compared to corresponding control groups. However, the values of CK and AST were significantly higher in WT-I than in KO-I. Mg in the treated tissue was significantly lower in WT-I in comparison to WT-C and KO-I, while there was no significant difference between KO-C and KO-I. There was no significant difference in Cu, Se, and Mn in the treated tissue between WT-C, KO-C, WT-I and KO-I. Gene expression of IL-33 in the treated tissue increased in both inflammatory groups when compared to the corresponding control groups, but it was significantly higher in KO-I than in WT-I. Gene expression of ST2 in the treated tissue was significantly higher in WT-I than in WT-C. Gene expression of TNF-alpha, IL-6, and IL-12p35 in the treated tissue was significantly higher in WT-I and KO-I than in the corresponding control groups, and IL-6 was significantly higher in KO-C than in WT-C. TGF-beta gene expression in the treated tissue was significantly higher in KO-I when compared to WT-I, while there was no difference between WT-C and KO-C. SOD activity decreased at the site of acute inflammation in both inflammatory groups, while the GPx activity increased. GSH in the treated tissue was significantly higher in KO-I than in KO-C or WT-I. CONCLUSION: The results of our study have indicated, to our knowledge for the first time, that IL-33/ST2 pathway plays a role in enhancing inflammation and tissue damage at the site of acute inflammation by affecting the concentration of magnesium and GSH, important for antioxidative capacity, as well as gene expression of anti-inflammatory cytokine TGF-beta.

Mitochondrial impairment, apoptosis and autophagy in a rat brain as immediate and long-term effects of perinatal phencyclidine treatment - influence of restraint stress.

Phencyclidine (PCP) acts as a non-competitive antagonist of glutamatergic N-methyl-d-aspartate receptor. Its perinatal administration to rats causes pathophysiological changes that mimick some pathological features of schizophrenia (SCH). Numerous data indicate that abnormalities in mitochondrial structure and function could be associated with the development of SCH. Mitochondrial dysfunction could result in the activation of apoptosis and/or autophagy. The aim of this study was to assess immediate and long-term effects of perinatal PCP administration and acute restraint stress on the activity of respiratory chain enzymes, expression of apoptosis and autophagy markers and ultrastructural changes in the cortex and hippocampus of the rat brain. Six groups of rats were subcutaneously treated on 2nd, 6th, 9th and 12th postnatal days (P), with either PCP (10mg/kg) or saline (0.9% NaCl). One NaCl and one PCP group were sacrificed on P13, while other two NaCl and PCP groups were sacrificed on P70. The remaining two NaCl and PCP groups were subjected to 1h restraint stress prior sacrifice on P70. Activities of respiratory chain enzymes were assessed spectrophotometrically. Expression of caspase 3 and AIF as markers of apoptosis and Beclin 1, p62 and LC3, as autophagy markers, was assessed by Western blot. Morphological changes of cortical and hippocampal ultrastructure were determined by transmission electron microscopy. Immediate effects of perinatal PCP administration at P13 were increased activities of complex I in the hippocampus and cytochrome c oxidase (COX) in the cortex and hippocampus implying mitochondrial dysfunction. These changes were followed by increased expression of apoptotic markers. However the measurement of autophagy markers at this time point has revealed decrease of this process in cortex and the absence of changes in hippocampus. At P70 the activity of complex I was unchanged while COX activity was significantly decreased in cortex and increased in the hippocampus. Expressions of apoptotic markers were still significantly higher in PCP perinatally treated rats in all investigated structures, but the changes of autophagy markers have indicated increased level of autophagy also in both structures. Restraint stress on P70 has caused increase of COX activity both in NaCl and PCP perinatally treated rats, but this increase was lower in PCP group. Also, restraint stress resulted in decrease of apoptotic and increase of autophagy processes especially in the hippocampus of PCP perinatally treated group. The presence of apoptosis and autophagy in the brain was confirmed by transmission electron microscopy. In this study we have demonstrated for the first time the presence of autophagy in PCP model of SCH. Also, we have shown increased sensitivity of PCP perinatally treated rats to restraint stress, manifested in alterations of apoptotic and autophagy markers. The future studies are necessary to elucidate the role of mitochondria in the pathophysiology of SCH and putative significance for development of novel therapeutic strategies.

Finasteride Has Regionally Different Effects on Brain Oxidative Stress and Acetylcholinesterase Activity in Acute Thioacetamide-Induced Hepatic Encephalopathy in Rats.

Finasteride (FIN) inhibits neurosteroid synthesis and potentially improves the course of hepatic encephalopathy (HE). This study aimed to investigate the effects of FIN on brain oxidative stress and acetylcholinesterase (AchE) activity in acute thioacetamide-induced HE in rats. Male Wistar rats were divided into groups: 1. control; 2. thioacetamide-treated group (TAA; 900 mg/kg); 3. finasteride-treated group (FIN; 150 mg/kg); 4. group treated with FIN and TAA (FIN+TAA). Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered intraperitoneally during three days and in FIN+TAA group FIN was administered 2h before every dose of TAA. FIN pretreatment prevented TAA-induced rise in malondialdehyde level in the cortex due to restoration of catalase activity and increased expression of superoxide dismutase 1 (SOD1) and induced an increase in malondialdehyde level in the thalamus due to reduction of glutathione peroxidase (GPx) and glutathione reductase (GR) activity. Although FIN pretreatment did not affect malondialdehyde level in hippocampus and caudate nucleus, hippocampal SOD1 expression was higher (p<0.05) and GR activity lower in FIN+TAA vs. TAA group (p<0.05). GPx activity was lower in caudate nucleus in FIN+TAA vs. TAA group (p<0.01). FIN pretreatment prevented TAA-induced rise in AchE activity in the thalamus and caudate nucleus and AchE activity correlates inversely in the thalamus (p<0.05) and positively in caudate nucleus (p<0.01) with malondialdehyde level. FIN has regionally selective effects on oxidative stress and AchE activity in the brain in acute TAA-induced HE in rats. The prooxidant role of FIN in the thalamus may be causally linked with inhibition of AchE.

Medical students' health-related quality of life--a comparative study.

BACKGROUND/AIM: Previous studies on medical students' subjective perception of health and health-related quality of life (HRQoL) showed inconclusive results. Moreover, there are no published studies to compare HRQoL of medical students to non-medical university students. The aim of the study was to assess subjective perception of health-related quality of life (HRQoL) in medical students' sample, to compare it with non-medical university students and to ascertain predictors of better perception of HRQoL in medical students. METHODS: Scores of all domains on the Mental and Physical Component Summary subscales and total score of the Short Form Health Survey (SF-36), used for assessment of HRQoL in samples of 561 medical and 332 non-medical university students were assessed and compared. In addition, linear regression to identify predictors of better perception of mental and physical components of HRQoL and overall HRQoL in the sample of medical students was used. The dependant variables were subscores and total score with the SF-36, and independent variables were certain sociodemographic and academic characteristics of the students. RESULTS: Medical students had statistically significantly higher scores on the Mental Component Summary and total SF-36 score compared to non-medical students. Linear regression analysis demonstrated that higher scores of Physical Component Summary were associated with age, male sex and the year of studies. The Mental Component Summary were associated with age, male sex, the year of studies and marital status. The total SF-36 score was associated with age, male sex and the year of studies. CONCLUSION: Medical students perceive their health much better than other university students do, but female, older and second grade medical students have worse perception of their HRQoL. Those points should be potential target areas for specific prevention and treatment in order to achieve better HRQoL.

Hyperhomocysteinemia induced by methionine dietary nutritional overload modulates acetylcholinesterase activity in the rat brain.

Methionine is the only endogenous precursor of homocysteine, sulfur-containing amino acid and well known as risk factor for various brain disorders. Acetylcholinesterase is a serine protease that rapidly hydrolyzes neurotransmitter acetylcholine. It is widely distributed in different brain regions. The aim of this study was to elucidate the effects of methionine nutritional overload on acetylcholinesterase activity in the rat brain. Males of Wistar rats were randomly divided into control and experimental group, fed from 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing to standard, 7.7 g/kg), respectively. On the 61st postnatal day, total homocysteine concentration was determined and showed that animals fed with methionine-enriched diet had significantly higher serum total homocysteine concentrations comparing to control rats (p < 0.01). Acetylcholinesterase activity has been determined spectrophotometrically in homogenates of the cerebral cortex, hippocampus, thalamus, and nc. caudatus. Acetylcholinesterase activity showed tendency to decrease in all examined brain structures in experimental comparing to control rats, while statistical significance of this reduction was achieved in the cerebral cortex (p < 0.05). Brain slices were stained with haematoxylin and eosin (H&E) and observed under light microscopy. Histological analysis of H&E-stained brain slices showed that there were no changes in the brain tissue of rats which were on methionine-enriched diet compared to control rats. Results of this study showed selective vulnerability of different brain regions on reduction of acetylcholinesterase activity induced by methionine-enriched diet and consecutive hyperhomocysteinemia.

[How do we treat generalized anxiety disorder?].

INTRODUCTION: In addition to significant prevalence of generalized anxiety disorder (GAD) and related consequences, it seems that this disorder has not been studied sufficiently in Serbia. OBJECTIVE: The aim of this study was to investigate the understanding of psychopathology and the adequate treatment of patients with GAD by psychiatrists in Serbia. METHODS: The study comprised 84 doctors - psychiatrists and neuropsychiatrists who were engaged in treatment of patients with GAD. Anonymous survey was used as the basic instrument, which collected information about the socio-demographic and professional data, experience in treating GAD and understanding psychopathology of GAD, as well as the first and the second choice therapy for patients with GAD. RESULTS: The majority of psychiatrists (62.2%) indicated the symptoms of distress/tension and slightly lower percent (36.6%) designated the symptoms of worry/anxiety as the key symptoms of GAD when it was diagnosed.The results showed that almost all patients (96.5%) had been treated with benzodiazepines before coming to psychiatrists. Most psychiatrists preferred the use of SSRI/SNRI antidepressants (76.2%), usually in combination with benzodiazepines (71.4%) for the treatment of patients with GAD; however, if these doctors got GAD, the preference of benzodiazepine use would be significantly lesser (45.2%) than for the treatment of their patients. Preference for the use of SSRI/SNRI antidepressants was significantly more frequent in physicians with completed residency. CONCLUSION: The understanding of psychopathology and treatment practice for patients with GAD in this sample of psychiatrists in Serbia is mostly consistent with the current trends for GAD treatment.

Oxidative stress precedes mitochondrial dysfunction in gerbil brain after aluminum ingestion.

Several studies suggest that aluminum (Al) intake might increase an individual's risk of developing Alzheimer disease. The dynamic of changes in acetylcholinesterase (AChE), cytochrome c oxidase (COX), Complex I, superoxide dismutase (SOD) and catalase (CAT) activities, and the lipid peroxide (MDA), superoxide anion (O2(-)) and thiol (SH) group levels in gerbil's brain after aluminum ingestion were analyzed. Gerbils that orally received aluminum chloride (LD25 or LD50) were sacrificed 2, 6 or 24 h later. Another group was subacutely treated (21 days; LD10). Controls received saline. Biochemical parameters were measured in cortex, hippocampus, thalamus and nucleus caudatus. Two hours after acute Al exposure AChE activity and SH group content were decreased and MDA and O2(-) levels were elevated in all investigated brain structures. The changes of COX and CAT were structure specific. SOD was increased after 6 h. Changes of investigated parameters were also seen after subacute Al treatment. These results might suggest the presence of additional source of free radicals in early phase of Al poisoning.

Risperidone reverses phencyclidine induced decrease in glutathione levels and alterations of antioxidant defense in rat brain.

Perinatal phencyclidine (PCP) administration to rats represents one of the actual animal models of schizophrenia. Numerous data suggest redox dysregulation in this disease. We have previously demonstrated decreased content of the reduced glutathione (GSH) and complex disbalance of antioxidant enzymes in the brain of rats perinatally treated with PCP. The aim of this study was to elucidate whether chronic risperidone treatment can reverse these changes. The Wistar rats were perinatally treated with either PCP (10mg/kg; PCP, two groups) or saline (0.9% NaCl, two groups). At postnatal day (PN) 35, two groups of rats one NaCl and one PCP have started to receive risperidone in drinking water for nine weeks (NaCl-RSP and PCP-RSP groups). Animals were sacrificed on PN100 and the levels of GSH, the activities of γ-glutamate cysteine ligase (GCL), glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase (SOD), as well as, the concentration of lipid peroxides were determined in the different brain structures. Risperidone restored decreased GSH levels, as well as decreased γ-GCL activity in cortex and hippocampus of animals perinatally treated with PCP. Alterations in GPx and GR activities caused by perinatal PCP treatment were also reversed by risperidone in most investigated brain structures. Furthermore, chronic risperidone treatment caused the decrease in SOD activity both in control and in PCP perinatally treated groups. Increased levels of lipid peroxides noticed in hippocampus and thalamus were reversed after chronic risperidone treatment. The results of the present study demonstrate that risperidone treatment restores GSH levels and to great measure reverses antioxidant defense alterations in the brain of perinatally PCP treated rats. Further studies are necessary in order to clarify the significance of risperidone influence on oxidative stress parameters in schizophrenia.

Psychiatrists' psychotropic drug prescription preferences for themselves or their family members.

BACKGROUND: Psychiatrists' preference for certain medications is not only determined by their efficacy and side effect profile but may also depend on the psychiatrists' beliefs about specific therapeutic effects based on their own observation and experience. We aimed to evaluate which antipsychotic or antidepressant drugs psychiatrists would prefer for themselves, their partners and children in case of a mental illness. SUBJECTS AND METHODS: The study was conducted among psychiatrists in Serbia. The sample consisted of 90 psychiatrists who were asked to complete the questionnaire about their drug selection in hypothetical situations of becoming ill with schizophrenia or depression or these conditions occurring in their partners and children. RESULTS: In case of schizophrenia, risperidone was the first choice made by most psychiatrists for themselves, their partners or children, followed by clozapine, haloperidol and olanzapine. In case of depression, SSRIs and SNRIs were generally favored, with sertraline and escitalopram being the preferred medications for psychiatrists, partners and their children. With regards to depression, 82.3% of participants would opt for an antidepressant as monotherapy or in combination, but 13.3% would opt for anxiolytic monotherapy. The preferred doses were slightly lower than the recommended ones, especially for antipsychotic agents. CONCLUSIONS: Most psychiatrists would take or administer atypical antipsychotics or SSRIs as the first choice for themselves, their partners or children. These preferences are mostly in accordance with current treatment guidelines, but there is still room to narrow the gap between guideline recommendations and psychiatrists' medication choices in personally meaningful situations.