Oxidatively-induced DNA base damage and base excision repair abnormalities in siblings of individuals with bipolar disorder DNA damage and repair in bipolar disorder.

Previous evidence suggests elevated levels of oxidatively-induced DNA damage, particularly 8-hydroxy-2'-deoxyguanosine (8-OH-dG), and abnormalities in the repair of 8-OH-dG by the base excision repair (BER) in bipolar disorder (BD). However, the genetic disposition of these abnormalities remains unknown. In this study, we aimed to investigate the levels of oxidatively-induced DNA damage and BER mechanisms in individuals with BD and their siblings, as compared to healthy controls (HCs). 46 individuals with BD, 41 siblings of individuals with BD, and 51 HCs were included in the study. Liquid chromatography-tandem mass spectrometry was employed to evaluate the levels of 8-OH-dG in urine, which were then normalized based on urine creatinine levels. The real-time-polymerase chain reaction was used to measure the expression levels of 8-oxoguanine DNA glycosylase 1 (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), poly ADP-ribose polymerase 1 (PARP1), and DNA polymerase beta (POLß). The levels of 8-OH-dG were found to be elevated in both individuals with BD and their siblings when compared to the HCs. The OGG1 and APE1 expressions were downregulated, while POLß expressions were upregulated in both the patient and sibling groups compared to the HCs. Age, smoking status, and the number of depressive episodes had an impact on APE1 expression levels in the patient group while body mass index, smoking status, and past psychiatric history had an impact on 8-OH-dG levels in siblings. Both individuals with BD and unaffected siblings presented similar abnormalities regarding oxidatively-induced DNA damage and BER, suggesting a link between abnormalities in DNA damage/BER mechanisms and familial susceptibility to BD. Our findings suggest that targeting the oxidatively-induced DNA damage and BER pathway could offer promising therapeutic strategies for reducing the risk of age-related diseases and comorbidities in individuals with a genetic predisposition to BD.

Effects of Repeated Doses of the Vero Cell Vaccine (SARS-Cov-2 Inactivated Vaccine) on Renal Functions in Balb/C Albino Mice.

Objective: Many of the vaccines developed for COVID-19 have been approved for clinical emergency use before their safety and preclinical studies have been completed. The main aim of this study was to investigate the effects of an inactivated SARS-CoV-2 virus vaccine (Vero cells) on renal function in Balb/C Albino mice. Methods: 21 healthy, 6-8 week old BALB/c male mice were divided into three equal groups, and 0.10 mL of intramuscular saline equal to the vaccine dose volume was administered to the first group. To the second group, a single dose of 0.10 mL 120 U of Vero cell inactive SARS COV-2 vaccine was administered intramuscularly. Group 3 received two consecutive doses of 0.10 mL 120 U intramuscular Vero cell inactive SARS COV-2 vaccine, 14 days apart. After administration, the clinical status, fecal and urine status, nutritional status and kidney histopathology of the mice were evaluated. Results: It was determined that no acute toxic symptoms were observed in the mice administered the vaccine, they were in good condition, and there was no significant stimulatory reaction related to the vaccine in the tissues of the injected local area. There was no difference in feed consumption, water consumption, and body weight gains between the control group, the groups that received a single dose of vaccine, and the groups that received two doses of vaccine (p>0.05). No difference was found between the groups when urine and feces amounts were compared (p>0.05). No difference was found between the groups when urinary urea, creatinine, and serum BUN, creatinine levels were compared (p>0.05). No difference was found in the histopathological evaluation of the kidneys between the groups (p>0.05). Conclusion: In conclusion, single or repeated injections of the SARS-CoV-2 vaccine (Vero cells) into mice were found to have no adverse effects on the animals' overall clinical health, performance abilities and kidneys.

Effects of nicorandil on QT prolongation and myocardial damage caused by citalopram in rats.

Citalopram is a selective serotonin re-uptake inhibitor (SSRI) antidepressant; it exhibits the greatest cardiotoxic effect among SSRIs. Citalopram can cause drug-induced long QT syndrome (LQTS) and ventricular arrhythmias. We investigated the protective effect of nicorandil, a selective mitochondrial KATP (mito-KATP) channel opener, on LQTS and myocardial damage caused by citalopram in male rats. In a preliminary study, we determined that the minimum citalopram dose that prolonged the QT interval was 102 mg/kg injected intraperitoneally. For the main study, rats were divided randomly into five experimental groups: untreated control, normal saline + citalopram, nicorandil + citalopram, 5-hydroxydecanoate (5-HD) + citalopram, 5-HD + nicorandil + citalopram. Biochemical and histologic data from blood and heart tissue samples from six untreated control rats were evaluated. Electrocardiographic parameters including QRS duration, QT interval, corrected QT interval (QTc) and heart rate (HR) were assessed, and biochemical parameters including malondialdehyde, reduced glutathione, glutathione peroxidase, superoxide dismutase were measured. We also performed histomorphologic and immunohistochemical examination of heart tissue. Citalopram prolonged QT-QTc intervals significantly and increased significantly the histomorphologic score and proportion of apoptotic cells, but produced no differences in the oxidant and antioxidant parameters. Nicorandil did not prevent citalopram induced QT-QTc interval prolongation and produced no significant changes in oxidant and antioxidant parameters; however, it did reduce histologic damage and apoptosis caused by citalopram.

Effect of the selective mitochondrial KATP channel opener nicorandil on the QT prolongation and myocardial damage induced by amitriptyline in rats.

OBJECTIVES: The aim of this study is to evaluate the protective effect of nicorandil, a selective mitochondrial KATP channel opener, on QT prolongation and myocardial damage induced by amitriptyline. METHODS: The dose of amitriptyline (intraperitoneal, i.p.) that prolong the QT interval was found 75 mg/kg. Rats were randomized into five groups the control group, amitriptyline group, nicorandil (selective mitochondrial KATP channel opener, 3 mg/kg i.p.) + amitriptyline group, 5-hdyroxydecanoate (5-HD, selective mitochondrial KATP channel blocker, 10 mg/kg i.p.) + amitriptyline group and 5-HD + nicorandil + amitriptyline group. Cardiac parameters, biochemical and histomorphological/immunohistochemical examinations were evaluated. p < 0.05 was accepted as statistically significant. KEY FINDINGS: Amitriptyline caused statistically significant prolongation of QRS duration, QT interval and QTc interval (p < 0.05). It also caused changes in tissue oxidant (increase in malondialdehyde)/anti-oxidant (decrease in glutathione peroxidase) parameters (p < 0.05), myocardial damage and apoptosis (p < 0.01 and p < 0.001). While nicorandil administration prevented amitriptyline-induced QRS, QT, QTc prolongation (p < 0.05), myocardial damage and apoptosis (p < 0.05), it did not affect the changes in oxidative parameters (p > 0.05). CONCLUSIONS: Our results suggest that nicorandil, a selective mitochondrial KATP channel opener, plays a protective role in amitriptyline-induced QT prolongation and myocardial damage. Mitochondrial KATP channel opening and anti-apoptotic effects may play a role in the cardioprotective effect of nicorandil.

Association between thyroid autoimmunity and antidepressant treatment-emergent mania in pediatric mood disorders.

Risk factors associated with antidepressant treatment-emergent mania(ATEM) are poorly characterized in child and adolescent populations. To identify better biomarkers, we aimed to explore whether thyroid autoimmunity is associated with ATEM in pediatric mood disorders. We enrolled two groups of pediatric mood disorders, those with ATEM+ (n = 29) and those with ATEM- controls (n = 31). All diagnoses were made according to structured interviews by the clinicians. Autoimmune thyroiditis (anti-thyroid peroxidase antibodies [TPO-abs] and thyroid function (thyroid-stimulating hormone [TSH] and free thyroxin [FT4]) were assessed. Logistic regression was used to explore the relationship between TPO-abs seroprevalence and ATEM+ while controlling for covariates. Group comparisons showed that the patient with ATEM+ had significantly higher seroprevalence and titer of TPO-abs compared to ATEM- controls. In logistic regression analysis adjusting for age, gender, Tanner stage, body mass index, antipsychotic treatments, smoking status and family history of thyroid disorder, the seroprevalence of TPO-abs (>60 U/mL) was significantly associated with ATEM+ (OR = 3.67, 95% confidence interval [CI] = 1.2-11.1, p = 0.022). Our findings demonstrated that seroprevalence and titer of TPO-abs in pediatric mood disorders are associated with ATEM+ status. TPO-abs could potentially serve as a biomarker when assessing the risk of ATEM in the child and adolescent population.

Protective effects of wheat germ oil against erectile and endothelial dysfunction in streptozotocin-induced diabetic rats.

Our aim was to investigate the protective effect of wheat germ oil (WGO) at different doses on diabetes mellitus (DM)-induced erectile and endothelial dysfunction. Twenty-four male Wistar rats weighing 250-300 g were divided into four groups as; control group treated with saline, DM group, DM group treated with 3 ml/kg WGO (DM + 3WGO group), DM group treated with 6 ml/kg WGO. Type 1 DM was induced by intraperitoneal injection of 60 mg/kg streptozotocin (STZ). STZ-induced diabetic rats received saline, 3 ml/kg WGO, and 6 ml/kg WGO via oral gavage daily for 5 weeks. The density of WGO used was 0.92 g/ml. The protective effect of WGO was evaluated by (i) in vitro vascular function, (ii) in vivo erectile function, and (iii) oxidative stress parameters in both aorta and penile tissue. Acetylcholine-mediated relaxation in the aorta and erectile functions decreased significantly in the DM group (p = 0.018 and p = 0.005). WGO (3 and 6 ml/kg) improved vascular functions in the DM groups (p = 0.001 and p = 0.014). The beneficial effect of WGO on erectile function appeared at higher doses of WGO. However, a higher dose of WGO substantially increased the oxidative stress parameters in both aorta and penile tissue. These findings suggest that the improvement in vascular or erectile function by WGO was not related to antioxidant effects, and new studies are needed to clarify the mechanism.

Brain-derived neurotrophic factor in bipolar disorder: Associations with age at onset and illness duration.

Bipolar disorder (BD) is a heterogeneous disorder that contains neurodevelopmental differences. Defining homogeneous subgroups of BD patients by using age at onset (AAO) as a specifier may promote the classification of biomarkers. This study compares peripheral BDNF levels between pediatric and adult BD patients to investigate the associations between BDNF levels, AAO, and illness duration. We enrolled two groups of euthymic patients, those with pediatric BD (n = 39) and those with adult BD (n = 31), as well as a group of healthy controls (HCs) (n = 90). Participants were assessed using clinical measures and BDNF serum levels were obtained using ELISA. We observed that BDNF levels were comparable between adult BD and HCs, but were clearly lower in pediatric BD than in HCs. In adult BD with AAO ≥30 years, BDNF levels were significantly higher than in adult BD with AAO <30 years. In pediatric BD, patients with prepubertal-onset had higher BDNF levels than those with pubertal-onset. BDNF levels demonstrated the accuracy of being able to distinguish pediatric BD from healthy controls in a receiver operating characteristic (ROC) curve analysis (area under the curve [AUC] = 0.792). In adult BD, higher BDNF levels were associated with later disease onset, but this was not the case in pediatric BD. Finally, reduced BDNF levels were associated with illness duration in adult BD. The findings indicate that BDNF levels in BD patients are associated with AAO. BDNF may, therefore, potentially serve as a developmental marker in BD, when AAO is taken into account.

Alterations in levels of 8-Oxo-2'-deoxyguanosine and 8-Oxoguanine DNA glycosylase 1 during a current episode and after remission in unipolar and bipolar depression.

INTRODUCTION: Previous studies showed significant increases in DNA base damage markers and significant alterations in base excision repair enzymes in patients with unipolar and bipolar depression. We aimed to investigate changes in urine 8-Oxo-2'-deoxyguanosine (8-oxo-dG) and gene expression levels of 8-Oxoguanine DNA glycosylase 1 (OGG1) during a current depressive episode and after remission in bipolar and unipolar disorders. METHODS: Twenty-four acutely depressed bipolar (BD), 33 unipolar depression (UD) patients and 61 healthy controls were included in the study. Clinical evaluations, blood and urine sampling were completed at baseline and at remission after eight weeks. The urine 8-oxo-dG levels were assessed by liquid chromatography tandem mass spectrometry and adjusted for urine creatinine levels. The gene expression levels of OGG1 were determined from cDNA extracted from blood samples, using real time-polymerase chain reaction. RESULTS: At baseline, patients presented significantly higher levels of 8-oxo-dG (p = 0.008), and lower gene expression of OGG1 (p = 0.024) compared to controls. Levels of either 8-oxo-dG or OGG1 expression did not differ between BD and UD. In patients who remitted by the 8th week (n = 30), 8-oxo-dG decreased significantly (p = 0.001), and gene expression levels of OGG1 increased by 2.95 times compared to baseline levels (p = 0.001). All comparisons were adjusted for age, sex, smoking status and body mass index. CONCLUSION: Our results suggest that patients with bipolar and unipolar mood disorders present increased 8-oxo-dG and decreased gene expression levels of OGG1 in current depressive episodes, and that these changes might be reversed by the resolution of depressive symptoms. The causal relationship between DNA damage and repair requires further exploration.

Do serum BDNF levels vary in self-harm behavior among adolescents and are they correlated with traumatic experiences?

The aim of this study was to compare serum brain-derived neurotrophic factor (BDNF) levels between adolescents that harm themselves, those that receive psychiatric treatment but do not harm themselves, healthy adolescents, and childhood traumas and to investigate the relationship between traumatic experiences and serum BDNF levels. The cases were divided into two groups of 40 adolescents exhibiting self-harm behavior (self-harm/diagnosed group) and 30 adolescents receiving psychiatric treatment but not exhibiting self-harm behaviors (non self-harm/diagnosed group). The control group (healthy control group) consisted of 35 healthy adolescents with no psychiatric disorders or self-harm behaviors. The adolescents were asked to fill in the Inventory of Statements About Self Injury (ISAS) and Childhood Trauma Questionnaire (CTQ). For BDNF measurement, blood samples were taken from the cases and controls. The serum BDNF level of self-harming adolescents who used the self-cutting method was significantly lower than that of other groups, and serum BDNF levels decreased with the increase in the emotional neglect and abuse severity of self-harming adolescents during childhood. In our study, serum BDNF levels decreased with the increase in emotional abuse in self-harming adolescents. This finding may indicate that neuroplasticity can be affected by a negative emotional environment during the early period.

Comparison of macular pigment optical density in patients with dry and wet age-related macular degeneration.

AIM: The aim of the study was to evaluate the macular pigment optical density (MPOD) levels in patients with wet age-related macular degeneration (AMD), dry AMD, and also in healthy controls. SETTINGS AND DESIGN: This study was conducted at Department of Ophthalmology, and the study design was a prospective study. PATIENTS AND METHODS: Forty-eight patients with wet AMD, 51 patients with dry AMD, and 50 controls were included in the study. All patients were naive to both previous lutein or zeaxanthin administration and any previous intravitreal injections. Fundus reflectance (VISUCAM 500, reflectance of a single 460 nm wavelength) was used to measure the MPOD levels. Three groups were compared regarding age, gender, serum lutein, and zeaxanthin concentrations as well as MPOD levels. RESULTS: Serum lutein and zeaxanthin levels were significantly higher in control group when compared with wet AMD (Group 1) and dry AMD (Group 2) (P = 0.001 and P< 0.001, respectively). Mean MPOD was found to be similar in all of the three study subgroups (P = 0.630). However, maximum MPOD was significantly higher in control group when compared with Group 1 and 2 (P = 0.003). There was no correlation between serum lutein or zeaxanthin concentrations and mean MPOD levels (P = 0.815, r = 0.014 and P = 0.461, r = 0.043, respectively), but there was a weak correlation between serum zeaxanthin concentration and maximum MPOD level (P = 0.042, r = 0.124). Maximum MPOD level was found to be correlated with the level of AMD (Group 1, 2, and 3; r = 0.184, P = 0.041). CONCLUSION: Maximum MPOD level was found to be lower in patients with AMD when compared with control cases. Mean MPOD and maximum MPOD levels were similar in wet and dry AMD Groups. These results can be applied clinically keeping in mind that MPOD measurements with one wavelength reflectometry may not be completely reliable.

Effect of Day and Night Desflurane Anaesthesia on Melatonin Levels in Rats.

OBJECTIVE: The aim of this study is to investigate the effect of day and night administration of desflurane anaesthesia on melatonin levels in rats. METHODS: Twenty-four 15-day-old rats were included in the study and were divided into four groups. The rats were anaesthetised between 19:00-01:00 (night group) and 07:00-13:00 (day group) with 5.7% desflurane concentration in 6 L min-1 100% oxygen. 6 L min-1 oxygen was administered to the control groups. At the end of 6 h of anaesthesia, blood samples were taken, and rats were sacrificed. Blood samples were centrifuged and melatonin levels from plasma samples were measured with radioimmunoassay. RESULTS: There was a statistically significant difference between the groups (p=0.007). Between group day control and group night control there was a statistically significant difference (p=0.042). Further, there was a significant difference between group day control and night desfluran as well (p=0.024). We could not find any difference between other groups. CONCLUSION: This study showed that 6 hours of 5.7% desflurane anaesthesia during day and night hours did not significantly change melatonin levels.

Effect of day/night administration of three different inhalational anesthetics on melatonin levels in rats.

The nocturnal peak of melatonin can be altered after anesthesia and surgery. We aimed to examine the melatonin levels during the day and night after anesthesia with three commonly used inhalational anesthetics. Forty-eight male Wistar albino rats were randomized into eight groups. Rats were administered anesthesia between 7:00 am and 1:00 pm (day groups) or 7:00 pm and 1:00 am (night groups) for 6 hours. At the end of the anesthesia, blood samples were collected for assessing melatonin levels. Mean values of melatonin levels after 6 hours of anesthesia during daytime were 43.17±12.95 for control, 59.79±27.83 for isoflurane, 50.75±34.28 for sevoflurane and 212.20±49.56 pg/mL for desflurane groups. The night groups' mean melatonin levels were 136.12±33.20 for control, 139.85±56.29 for isoflurane, 117.48±82.39 for sevoflurane and 128.70±44.63 pg/mL for desflurane groups. Desflurane anesthesia between 7:00 am and 1:00 pm significantly increased melatonin levels (p<0.001). Sevoflurane and desflurane anesthesia between 7:00 pm and 1:00 am decreased the melatonin levels but there were no significant differences (p=0.904 and p>0.99, respectively). Isoflurane anesthesia did not significantly change melatonin levels during day or night (p=0.718 and p>0.99, respectively). Our results demonstrate that during daytime desflurane anesthesia can alter melatonin levels. Altered melatonin rhythm following inhalational anesthesia can be related to sleep disorders observed after anesthesia.

Artificial Neural Network Approach in Laboratory Test Reporting: Learning Algorithms.

OBJECTIVES: In the field of laboratory medicine, minimizing errors and establishing standardization is only possible by predefined processes. The aim of this study was to build an experimental decision algorithm model open to improvement that would efficiently and rapidly evaluate the results of biochemical tests with critical values by evaluating multiple factors concurrently. METHODS: The experimental model was built by Weka software (Weka, Waikato, New Zealand) based on the artificial neural network method. Data were received from Dokuz Eylül University Central Laboratory. "Training sets" were developed for our experimental model to teach the evaluation criteria. After training the system, "test sets" developed for different conditions were used to statistically assess the validity of the model. RESULTS: After developing the decision algorithm with three iterations of training, no result was verified that was refused by the laboratory specialist. The sensitivity of the model was 91% and specificity was 100%. The estimated κ score was 0.950. CONCLUSIONS: This is the first study based on an artificial neural network to build an experimental assessment and decision algorithm model. By integrating our trained algorithm model into a laboratory information system, it may be possible to reduce employees' workload without compromising patient safety.

Amyloid Beta Peptides Affect Pregnenolone and Pregnenolone Sulfate Levels in PC-12 and SH-SY5Y Cells Depending on Cholesterol.

Increased amyloid beta (AB) peptide concentration is one of the initiating factors in the neurodegeneration process. It has been suggested that cholesterol induces the synthesis of AB peptide from amyloid precursor protein or facilitates the formation of amyloid plaque by lowering the aggregation threshold of the peptide. It is also shown that AB peptides may affect cholesterol metabolism and the synthesis of steroid hormones such as progesterone and estradiol. Pregnenolone (P) and pregnenolone sulfate (PS) are the major steroids produced from cholesterol in neural tissue. In toxicity conditions, the effect of AB peptides on P and PS levels has not yet been determined. Furthermore, it has not been clearly defined how changes in cellular P and PS levels affect neuronal cell survival. The aim of this study was to determine the effects of AB peptides on cellular changes in P and PS levels depending on the level of their main precursor, cholesterol. Cholesterol and toxic concentrations of AB fragments (AB 25-35, AB 1-40 and AB 1-42) were applied to PC-12 and SH-SY5Y cells. Changes in cellular cholesterol, P and PS levels were determined simultaneously in a dose-and time-dependent manner. The cell viability and cell death types were also evaluated. AB peptides affected both cell viability and P/PS levels. Steroid levels were altered depending on AB fragment type and the cholesterol content of the cells. Treatment with each of the AB fragments alone increased P levels by twofold. However, combined treatment with AB peptides and cholesterol increased P levels by approximately sixfold, while PS levels were increased only about 2.5 fold in both cell lines. P levels in the groups treated with AB 25-35 were higher than those in AB 1-40 and AB 1-42 groups. The cell viabilities were significantly low in the group treated by AB and cholesterol (9 mM). The effect of AB peptides on P levels might be a result of cellular self-defense. On the other hand, the rate of P increase might be playing a key role in the cell death mechanism of AB toxicity depending on cellular cholesterol levels.

A multicenter nationwide reference intervals study for common biochemical analytes in Turkey using Abbott analyzers.

BACKGROUND: A nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality. METHODS: Blood samples were collected nationwide in 28 laboratories from the seven regions (≥400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA). RESULTS: By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and γ-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/m2. Ranges of RIs by non-parametric method were wider than those by parametric method especially for those analytes affected by BMI. CONCLUSIONS: With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population.

Alterations in BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) serum levels in bipolar disorder: The role of lithium.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) has been consistently reported to be decreased in mania or depression in bipolar disorders. Evidence suggests that Glial cell line-derived neurotrophic factor (GDNF) has a role in the pathogenesis of mood disorders. Whether GDNF and BDNF act in the same way across different episodes in bipolar disorders is unclear. METHOD: BDNF and GDNF serum levels were measured simultaneously by enzyme-linked immunosorbent assay (ELISA) method in 96 patients diagnosed with bipolar disorder according to DSM-IV (37 euthymic, 33 manic, 26 depressed) in comparison to 61 healthy volunteers. SCID- I and SCID-non patient version were used for clinical evaluation of the patients and healthy volunteers respectively. Correlations between the two trophic factor levels, and medication dose, duration and serum levels of lithium or valproate were studied across different episodes of illness. RESULTS: Patients had significantly lower BDNF levels during mania and depression compared to euthymic patients and healthy controls. GDNF levels were not distinctive. However GDNF/BDNF ratio was higher in manic state compared to euthymia and healthy controls. Significant negative correlation was observed between BDNF and GDNF levels in euthymic patients. While BDNF levels correlated positively, GDNF levels correlated negatively with lithium levels. Regression analysis confirmed that lithium levels predicted only GDNF levels positively in mania, and negatively in euthymia. LIMITATIONS: Small sample size in different episodes and drug-free patients was the limitation of thestudy. CONCLUSION: Current data suggests that lithium exerts its therapeutic action by an inverse effect on BDNF and GDNF levels, possibly by up-regulating BDNF and down-regulating GDNF to achieve euthymia.

The effect of malnutrition on protein glycosylation in children.

OBJECTIVE: The goal of this study was to evaluate the effect of protein energy malnutrition on protein glycosylation by investigating transferrin isoform pattern and its relationship to the degree of malnutrition and the biochemical markers of nutritional status in children. METHODS: Forty one children with mild (n=23) and severely/moderately (n=18) acute malnutrition and 29 controls were enrolled in the study. Serum transferrin isoforms were determined by isoelectric focusing electrophoresis. Transferrin, prealbumin, zinc, iron and insulin-like growth factor-1 (IGF-1) were measured using automated analyzers. Findings : Asialotransferrin and disialotransferrin were significantly higher in severely/moderately malnourished patients compared to controls (P=0.04 and P=0.04, respectively). Other transferrin isoform patterns were not different among three groups. Serum IGF-1, transferrin and iron levels of severely/ moderately malnourished group were significantly lower than tose of controls (P=0.001, 0.02 and 0.03, respectively). Serum prealbumin and zinc levels were similar in all three groups. Serum IGF-1, transferrin and iron levels, and all transferrin isoform patterns were not significantly different in mildly malnutrition group from other two groups. CONCLUSION: The changes in transferrin isoform pattern observed in malnourished patients may indicate that malnutrition is a catabolic state which has effects on glycosylation.

New generation IQ-200 automated urine microscopy analyzer compared with KOVA cell chamber.

OBJECTIVE: The examination of the urine remains to be one of the most commonly performed tests in laboratory practice. Currently, laboratories also need to accredit their urine diagnostics by comparing their measurement methods to acceptable references. In this study we compared particle counts obtained by new generation automated technique, image capture analysis (IQ-200) with those of a standardized chamber counts. DESIGN AND METHODS: The same 258 urine samples from different departments of a hospital assayed by IQ-200 were analyzed in parallel with the KOVA cell chamber system. Clinically significant discrepancy results (positive vs. negative) for red blood cell (RBC) and white blood cell (WBC) were also compared with those obtained by dipstick testing. RESULTS: There was a good agreement between the automated system and sediment microscopy for RBCs, WBCs, and squamous epithelial cells (SCs) (r=0.90; r=0.80; r=0.72, respectively: P<0.001). The IQ-200 was more sensitive for determining RBCs, WBCs, and SCs than other formed elements. CONCLUSIONS: IQ-200 can perform accurate quantification of microscopic element in urine. However, automated techniques are not completely free of error. Therefore, by adopting an appropriate algorithm and combining the results with stript analysis and other laboratory tests allows further reduction of clinically important errors.

Pregnenolone protects the PC-12 cell line against amyloid beta peptide toxicity but its sulfate ester does not.

Pregnenolone (P), the main precursor of the steroids, and its sulfate ester, pregnenolone sulfate (PS), are the major neurosteroids produced in the neural tissue. Many neuroendocrinological studies stressed the neuroprotective role of neurosteroids although it has been suggested that the inhibition of P and PS synthesis can delay neuronal cell death. The potential roles of P and PS in vital neuronal functions and in amyloid beta peptide (Abeta) toxicity are not clearly identified. This work aims to investigate the effects of P and PS on cell viability and Abeta peptide toxicity in a concentration and exposure time-dependent manner in rat PC-12 cells. The cells were treated with 20muM Abeta peptide 25-35 and variable concentrations of P and PS ranging from 0.5muM to 100muM. To examine the effects of steroid treatment on Abeta peptide toxicity, 0.5muM (low) and 50muM (high) neurosteroids were used. The cell viability and lactate dehydrogenase release of cells were evaluated after 24, 48 and 72h. Morphological changes of cells were also examined. The treatment with higher than 1muM concentrations of P and PS significantly decreased the cell viability comparing to untreated cells. At lower concentrations, P and PS had no toxic actions until 72h. The Abeta treatment resulted in a significant decrease in cell viability comparing to untreated cells. P showed a dose-dependent protective effect against Abeta peptide in PC-12 cells. But its sulfate ester did not have the same effect on Abeta peptide toxicity, even it significantly decreased cell viability in Abeta-treated cells. Consequently, the discrepant effects of P and PS on Abeta peptide toxicity may provide insight on the pathogenesis of Alzheimer's disease.