Paliperidone regulates intracellular redox system in rat brain: Role of purine mechanism.

OBJECTIVE: The treatment of schizophrenia is multifactorial, with antipsychotic medications comprising a major part of treatment. Paliperidone is a newly commercialized antipsychotic whose formulation includes the principal active metabolite risperidone, 9-hydroxyrisperidone. Ever since the relationship between schizophrenia and oxidative stress was first demonstrated, many studies have been conducted in order to probe the potential protective effects of antipsychotic drugs on the oxidant-antioxidant system and lipid peroxidation. The basic aim of this study is to determine the effects of the newly marketed drug paliperidone on the activities of the enzymes adenosine deaminase (ADA), xanthine oxidase (XO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) as well as on malondialdehyde (MDA) and nitric oxide (NO) levels in rat brain tissues. METHODS: Twenty male Sprague-Dawley rats were used for the study, which were divided into two equal groups. The first was the control group (n = 10) and the second was the paliperidone group (n = 10). Saline was administered once daily for 14 days in the control group. In the paliperidone group, paliperidone was administered once daily with a dose of 1 mg/kg for 14 days. All rats were sacrificed at the end of the fourteenth day. Brain samples were collected and then analyzed. RESULTS: Our results demonstrated that paliperidone significantly decreased the activities of ADA (P = 0.015), XO (P = 0.0001), and CAT (P = 0.004) while insignificantly increasing the activity of SOD (P = 0.49), MDA (P = 0.71), and NO (P = 0.26) levels in rat brain tissues. In addition, paliperidone insignificantly decreased the activity of GSH-Px (P = 0.30) compared to the control group in rat brain tissues. DISCUSSION: In conclusion, the data obtained in this study suggest that paliperidone can positively alter antioxidant status and, accordingly, can offer positive outcomes in the treatment of schizophrenia by reducing activity in the enzymes ADA and XO, which are associated with purine metabolism. We believe that such a comprehensive approach used with other antipsychotic drugs warrants further study.

Late-life Onset Mania After Varenicline Use: A Case Report.

Late-life onset manic attacks generally occur secondary to general medical conditions or drug use. Varenicline is an α4ß2 nicotinic acetylcholine receptor partial agonist, used for the cessation of smoking. In this case report, we present a 67-year-old male patient with a new-onset manic episode following varenicline treatment. The patient's manic symptoms started on the seventh day of varenicline treatment. His symptoms started on the 7th day of treatment. He was admitted to the psychiatric outpatient clinic since his symptoms did not improve despite discontinuing varenicline treatment. In the initial mental status examination, he scored 35/60 on the Young Mania Rating Scale (YMRS). On the twenty-fifth day of the hospitalization, the patient was discharged since his YMRS score improved (5/60). Varenicline may cause manic episodes in patients with bipolar disorder and in healthy individuals. An increasing number of serious psychiatric disorders are being reported due to varenicline treatment. Mental state examination before and during varenicline treatment seems necessary.

Acamprosate modulates alcohol-induced hippocampal NMDA receptors and brain microsomal Ca2+-ATPase but induces oxidative stress in rat.

We investigated the effects of acamprosate on alcohol-induced oxidative toxicity, microsomal membrane Ca(2+)-ATPase (MMCA) activity and N-methyl-D: -aspartate receptor (NMDAR) subunits in rat brain. Forty male rats were equally divided into four groups. The first group was used as control, and the second group received ethanol. Acamprosate and acamprosate plus ethanol each day were administered to rats constituting the third and fourth groups for 21 days, respectively. Brain cortical and hippocampal samples were taken from the four groups after 21 days. Brain cortical lipid peroxidation (LP) levels and MMCA activity were higher in the alcohol group than in control, although glutathione peroxidase (GSH-Px), vitamin C, vitamin E and ß-carotene values were lower in the alcohol group than in control. LP levels were further increased in the acamprosate and alcohol + acamprosate groups compared with the alcohol group. GSH-Px, vitamin A, vitamin C, vitamin E and ß-carotene in the acamprosate and alcohol + acamprosate groups were further decreased compared with the alcohol group. Hippocampal NMDAR 2A and 2B subunit concentrations were lower in the alcohol group than in control, although they were increased by acamprosate and alcohol + acamprosate. Brain cortical MMCA activity was higher in the acamprosate group than in the alcohol-treated rats, although its activity was lower in the alcohol + acamprosate group than in the acamprosate group. Brain cortical reduced glutathione levels were not found to be statistically different in any of the groups. Oxidative stress has been proposed to explain the biological side effects of experimental alcohol intake. Acamprosate and alcohol-induced oxidative stress decreased brain antioxidant vitamins in the alcoholic rats.

Fish oil and antipsychotic drug risperidone modulate oxidative stress in PC12 cell membranes through regulation of cytosolic calcium ion release and antioxidant system.

Oxidative stress is a critical route of damage in various psychological disorders such as schizophrenia, although fish oil and risperidone (RISP) induce antioxidant effects in the human body. However, the mechanisms behind these effects remain elusive. We investigated the effects of fish oil and RISP in the PC12 cell line by evaluating Ca(2+) mobilization, lipid peroxidation (LP) and antioxidant levels. PC12 cells were divided into eight flasks: control, fish oil, RISP, H(2)O(2), fish oil + H(2)O(2), RISP + H(2)O(2), fish oil + RISP and fish oil + RISP + H(2)O(2). Cells were incubated with fish oil and RISP for 24 and 48 h, respectively. Then, cells were exposed to H(2)O(2) for 15 min before analysis. Ca(2+) release and LP levels were higher in the H(2)O(2) group than in the control, RISP and fish oil groups, although their levels were decreased by incubation of cells in fish oil and RISP. Glutathione peroxidase activity, reduced glutathione and vitamin C levels in the cells were lower in the H(2)O(2) group than in the control, RISP and fish oil groups, although levels were higher in cells incubated with fish oil and RISP than in those in the H(2)O(2) groups. In conclusion, these results indicate that RISP and fish oil induced protective effects on oxidative stress in PC12 cells by modulating cytosolic Ca(2+) release and antioxidant levels.

[Relationship between blood glucose control and psychiatric disorders in type II diabetic patients]. / Tip II diabetik hastalarda kan sekeri kontrolü ile psikiyatrik bozukluklarin iliskisi.

OBJECTIVE: To explore specific psychiatric comorbidity among type II DM patients with poor and good glycemic control. METHOD: One hundred four patients with type II DM attending outpatient department of the Endocrinology Unit of Süleyman Demirel University Medical Faculty were included in this study. Patients were divided into two groups according to HbA1c level: >7% defined group 1 with poor glycemic control (n=40), and <7% defined group 2 with good glycemic control (n=64). All patients were assessed using a semi structured sociodemographic data form, the Structured Clinical Interview for DSM-IV-Clinical Version (SCID-I/CV), Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS) and the Minimental State Examination Scale. RESULTS: The prevalence rate of psychiatric disorders were as follows: major depressive disorder 67.5%, dysthymic disorder 10.0%, generalized anxiety disorder 7.5%, obsessive compulsive disorder 5%, social phobia 2.5% and nicotine dependence 5% in group 1 patients; and major depressive disorder 43.8%, dysthymic disorder 10.9%, paranoid disorder 3.1%, obsessive compulsive disorder 6.3%, social phobia 4.7%, generalized anxiety disorder 6.3%, nicotine dependence 9.4% and alcohol dependence 3.1% in group 2 patients. Major depressive disorder frequency was significantly higher in group1 patients than group 2 patients. HDRS and HARS scores were significantly higher in group 1 patients than in group 2 patients. Significant positive correlations were found between HDRS, HARS scores, number of depressive episodes and the level of HbA1c in the diabetic patients. CONCLUSION: Major depressive disorder was more frequent in diabetic patients with poor glycemic control than in those with good glycemic control. There was a strong association between level of HbA1c and depression and anxiety symptom level.

Effect of cigarette smoke on lipid peroxidation, antioxidant enzymes and NMDA receptor subunits 2A and 2B concentration in rat hippocampus.

The effect of cigarette smoke on lipid peroxidation and antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and on the concentration of N-methyl-d-aspartate receptor (NMDAR) subunits 2A and 2B in the hippocampus of Sprague-Dawley rats exposed to cigarette smoke for 2h/day for a period of 4 weeks was determined. It was observed that NMDAR 2A and 2B concentrations in the hippocampus were enhanced in the case of animals exposed to cigarette smoke, whereas lipid peroxidation and antioxidant enzyme activities did not show any change as compared to control animals. The results of our study suggest that cigarette smoke induces NMDAR 2A and 2B expression in the hippocampus, and that this is not due to an increased lipid peroxidation, because cigarette smoke has no effect on lipid peroxidation and antioxidant enzyme activities in the hippocampus.

Psychological symptoms are greater in caregivers of patients on hemodialysis than those of peritoneal dialysis.

BACKGROUND: The purpose of this study was to evaluate and compare psychosocial characteristics in caregiving relatives (caregivers) of hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: Thirty-three caregivers (17 women, 16 men) of HD patients, 27 caregivers (11 women, 16 men) of PD patients, and a control group of 49 subjects who do not care for family members with chronic illness (23 women, 26 men) are included in this study. The brief symptom inventory (BSI), social disability schedule (SDS), and brief disability questionnaire (BDQ) were used for the psychosocial evaluation. RESULTS: The mean age, men-to-women ratios, duration of education, and distribution of marital status did not differ significantly among the three groups. In addition, dialysis duration and distribution of caregiver type were not different between the HD and PD groups. Although the mean global severity index scores of the three groups were similar, somatization and depression scores from BSI subitems were greater in the HD group than the scores of the PD and control groups. Although the mean SDS and BDQ scores were higher in the HD group, the differences did not achieve statistical significance. BSI subitems such as somatization, obsession-compulsion, interpersonal sensitivity, depression, and anxiety were positively correlated among themselves. Hostility and somatization were negatively correlated with age and education, respectively. Nevertheless, somatization was positively correlated with age. Social disability was negatively correlated with duration of education. CONCLUSION: Somatization and depression are greater in the caregivers of center HD patients compared to PD and control groups. According to the findings of this study, we suggest that caregiving family members of dialysis patients especially on HD also should be evaluated for psychosocial problems and supported as needed. Further studies are needed to explore whether psychosocial parameters of caregivers predict outcomes for caregivers and patients.

Clinical importance of erythrocyte malondialdehyde levels as a marker for cognitive deterioration in patients with dementia of Alzheimer type: a repeated study in 5-year interval.

OBJECTIVES: The aim of the present study was to determine the effects of aging and dementia of the Alzheimer type (DAT) on lipid peroxidation and antioxidant enzyme activities. DESIGN AND METHODS: Twenty-six patients with DAT were included in the present study. Group I: 26 patients diagnosed as DAT and studied 5 yr ago. Group II: This group consisted of the same patients as Group I at the present time. Activities of CuZn superoxide dismutase (CuZn SOD) and glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) concentrations of these 26 subjects were measured and mini mental state examination (MMSE), brief psychiatric rating scale (BPRS), Hamilton depression rating scale (HDRS) were applied. RESULTS: The results revealed that 26 dementia patients had worsened cognitive symptoms and significantly increased CuZn SOD and MDA levels and decreased GSH-Px levels after 5 yr. Significant correlation was found between age and CuZn SOD (r: +0.406, p: 0.034), and between MMSE and MDA (r: -0.411, p: 0.032). CONCLUSIONS: We can conclude that MDA, CuZn SOD, and GSH-Px were significantly affected in the patients with Alzheimer disease. The most striking finding of this study is the significant correlation between MMSE and MDA in patients with DAT.

Malondialdehyde, superoxide dismutase, melatonin, iron, copper, and zinc blood concentrations in patients with Alzheimer disease: cross-sectional study.

AIM: To investigate the oxidative stress hypothesis in patients with Alzheimer type dementia. METHOD: Serum melatonin, Zn, Cu, Fe, and malondialdehyde (MDA) concentrations and erythrocyte superoxide dismutase (SOD) activity were measured in patients with Alzheimer disease. Mini-Mental State Examination (MMSE) scores were obtained for the patients and their age- and sex-matched healthy controls. RESULTS: MMSE score was 16.81.3 in patients with Alzheimer disease, and 28.22.4 in control group. Melatonin levels were lower in the Alzheimer disease group (170.55.2 pg/mL) than in the control group (205.25.8 pg/mL) (p<0.001). Fe, SOD, and MDA levels were higher in Alzheimer disease group (131.74.8 microg/dL, 1,51090 U/g Hb, and 38.14.7 nmol/mL; respectively) than in the control group (97.14.1 microg/dL, 1,12050 U/g Hb, and 17.21.6 nmol/mL; respectively) (p<0.001 for all comparisons). A statistically significant negative correlation between melatonin and SOD (r=-0.421, p=0.014) and a positive correlation between age and Fe (r=0.325, p=0.049) were found only in the Alzheimer disease group. Correlation between age and melatonin was positive (r=0.481, p=0.006) in Alzheimer disease group and negative (r=-0.472, p=0.009) in the control group. CONCLUSION: Melatonin blood concentration was significantly decreased, and Fe and MDA levels were increased in the patients with Alzheimer disease. We believe that low level of melatonin, especially if there is a simultaneous increase in Fe level, is associated with the development of Alzheimer disease.