The Relationship between the Number of Manic Episodes and Oxidative Stress Indicators in Bipolar Disorder.

OBJECTIVE: Bipolar disorder (BD) is a chronic mood disorder characterized by recurrent episodes that has a lifetime prevalence of 0.4- 5.5%. The neurochemical mechanism of BD is not fully understood. Oxidative stress in neurons causes lipid peroxidation in proteins associated with neuronal membranes and intracellular enzymes and it may lead to dysfunction in neurotransmitter reuptake and enzyme activities. These pathological processes are thought to occur in brain regions associated with affective functions and emotions in BD. The relationship between the number of manic episodes and total oxidant-antioxidant capacity was investigated in this study. METHODS: Eighty-two BD patients hospitalized due to manic symptoms and with no episodes of depression were enrolled in the study. Thirty of the 82 patients had had their first episode of mania, and the other 52 patients had had two or more manic episodes. The control group included 45 socio-demographically matched healthy individuals. Serum total antioxidant capacity (TAC) and total oxidant capacity (TOC) measurements of the participants were performed. The oxidative stress index (OSI) was calculated by TOC/TAC. RESULTS: There were no significant differences in OSI scores between BD patients with first-episode mania and BD patients with more than one manic episode. However, OSI scores in both groups were significantly higher than in the control group. TOC levels of BD patients with first-episode mania were found to be significantly higher than TOC levels of BD patients with more than one manic episode and healthy controls. There were no significant differences in TAC levels between BD patients with first-episode mania and BD patients with more than one manic episode. TAC levels in both groups were significantly higher than in the control group. CONCLUSION: Significant changes in oxidative stress indicators were observed in this study, confirming previous studies. Increased levels of oxidants were shown with increased disease severity rather than with the number of manic episodes. Systematic studies, including of each period of the disorder, are needed for using the findings indicating deterioration of oxidative parameters.

Polycystic Ovary Syndrome and Increased Soluble Tumor Necrosis Factor Like Weak Inducer of Apoptosis Levels Are Independent Predictors of Dyslipidemia in Youth.

BACKGROUND/AIMS: Dyslipidemia is common in women with polycystic ovary syndrome (PCOS) irrespective of age. Our aim was to investigate soluble tumor necrosis factor like weak inducer of apoptosis (sTWEAK), a cardiovascular risk marker in PCOS, and to determine if it is associated with dyslipidemia in youth. METHODS: A prospective-observational study was carried out including 35 PCOS patients and 35 healthy controls. Serum sTWEAK levels were measured using commercially available kits. Multiple logistic regression analysis was then performed to verify the statistically significant differences in the possible predictors of dyslipidemia. RESULTS: Serum sTWEAK levels and the percentage of women with dyslipidemia were significantly higher in the PCOS group (p = 0.024 and p < 0.001, respectively). Participants were further divided into 2 subgroups based on the presence of dyslipidemia. The percentage of women with PCOS was significantly higher in the dyslipidemic group when compared with controls; 70.7 vs. 20.7%, respectively (p < 0.001). Multiple logistic regression analysis revealed that both the presence of PCOS (OR 7.924, 95% CI 2.117-29.657, p = 0.002) and increased levels of sTWEAK (>693 pg/ml; OR 3.810, 95% CI 1.075-13.501, p = 0.038) were independently associated with dyslipidemia. CONCLUSIONS: Increased levels of both sTWEAK and PCOS were found to be independently associated with dyslipidemia in youth.

Evaluation of Etanercept Treatment in Newborn Rat Model with Hyperoxic Lung Injury.

BACKGROUND: Many factors contribute to the development of BPD basically by increasing inflammation in preterm lungs. However, premature neonates have insufficient anti-inflammatory capacity. We aimed to evaluate the effect of etanercept, an anti-TNF agent, on BPD development in newborn rat model with hyperoxia-induced lung injury. METHODS: Thirty-two newborn rats were divided into 3 groups as control group (Group 1, n = 11), hyperoxia + placebo group (Group 2, n = 10), and hyperoxia + etanercept group (Group 3, n = 11). Histopathological and biochemical analysis were performed in order to assess inflammation and oxidative stress. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, and malondialdehyde (MDA) levels were studied, histopathological scoring and radial alveolar count were applied in lung tissue. Lamellar body membrane protein, vascular endothelial growth factor (VEGF), nuclear factor-kappaB (NF-κB) gene expressions were studied in immunohistochemical evaluation of tissue samples. All three groups were compared with each other in terms of all parameters. RESULTS: SOD and GSH-Px activities were significantly higher, whereas MDA levels were lower in group 3, compared to group 2 (p < 0.001). Histopathological scores were lower, lamellar body membrane protein expression and radial alveolar count were higher in group 3 (p < 0.05). NF-κB expression was higher in group 2, but lower in group 3 in comparison with group 1. Expression of VEGF was decreased in group 2 but came close to group 1 with etanercept treatment in group 3. CONCLUSIONS: We found etanercept treatment to be protective in newborn rats with hyperoxia-induced lung damage.

Myostatin as a Marker for Doxorubicin Induced Cardiac Damage.

PURPOSE: Doxorubicin (DXR) is an effective chemotherapeutic agent but causes severe cardiac failure over known doses. Thus, early detection and prevention of cardiac damage is important. Various markers have been tested for early detection of cardiac damage. Myostatin is a protein produced in skeletal muscle cells inhibits muscle differentiation and growth during myogenesis. METHODS: We evaluated the role of myostatin as a marker for showing DXR induced cardiac damage and compared with well known cardiac markers like NT-proBNP, hs-TnT and CK in a rat model of chronic DXR cardiotoxicity. RESULTS: Myostatin, NT-proBNP, and hs-TnT but not CK rose significantly during DXR treatment. CONCLUSION: Myostatin can be used as an early marker of DXR induced cardiotoxicity.

How important is the butyrylcholinesterase level for cesarean section?

OBJECTIVES: Butyrylcholinesterase (BChE), commonly known as pseudocholinesterase or non-neural cholinesterase, hydrolyzes neuromuscular blocker agents containing choline esters such as succinylcholine that is widely used in rapid sequence induction (RSI) for general anesthesia. The aim of this study is to compare plasma BChE levels and investigate the affects and relationship of succinylcholine on BChE levels in preeclamptic, gestational diabetic and healthy pregnants. STUDY DESIGN: We designed a prospective, controlled, pilot single-center study. Thirty (n=30) pregnant women who were scheduled for cesarean section under general anesthesia (refusal of regional anesthesia) with RSI involved. Group 1 included ten (n=10) preeclamptic pregnancies, Group 2 included ten (n=10) gestational diabetic (GD) pregnancies and Group 3 included ten (n=10) healthy pregnancies. MAIN OUTCOME MEASURES: BChE levels of all patients were measured prior to the initiation of cesarean section. Train-of-four recovery of 90% (TOF T1) was used to monitor the degree of neuromuscular block beginning from the administration of succinylcholine. RESULTS: No statistically significant difference was found between the groups comparing BChE levels and the duration between tracheal intubation and formation of TOF T1 (p>0.05). CONCLUSIONS: As similar results were gathered from normal and high-risk pregnancies (preeclamptic pregnancy or gestational diabetic pregnancy) who underwent cesarean section under general anesthesia, we believe that succinylcholine is still neuromuscular agent of choice in cesarean section.

Adult polyglucosan body disease presenting as a unilateral progressive plexopathy.

INTRODUCTION: Adult polyglucosan body disease (APBD) usually presents with progressive spastic paraparesis, neurogenic bladder, and distal lower limb sensory abnormalities. It is caused by mutations in the glycogen branching enzyme gene (GBE1). METHODS: We describe a woman with an unusual phenotype manifesting as progressive left brachial more than lumbosacral plexopathies, with central sensory and corticospinal tract involvement. RESULTS: Magnetic resonance imaging of the brain and cervical spine showed abnormal T2 signal within the ventral pons and medulla bilaterally, involving the pyramidal tracts and the medial leminisci. There was also medullary and cervical spine atrophy. On nerve biopsy, large polyglucosan bodies were noted in the endoneurium. The patient was found to be compound heterozygous for 2 novel mutations in GBE1. Peripheral blood leukocyte GBE activity was markedly reduced to 7% of normal, confirming the diagnosis of APBD. CONCLUSIONS: In this report we describe a new phenotype of APBD associated with 2 novel mutations. Muscle Nerve 53: 976-981, 2016.

A De Novo Mutation in MTND6 Causes Generalized Dystonia in 2 Unrelated Children.

Dystonia is often associated with the symmetrical basal ganglia lesions of Leigh syndrome. However, it has also been associated with mitochondrial ND mutations, with or without Leber hereditary optic neuropathy. The m.14459G>A mutation in ND6 causes dystonia with or without familial Leber hereditary optic neuropathy. We report heteroplasmic 14459G>A mutations in 2 unrelated children with nonmaternally inherited generalized dystonia and showing bilateral magnetic resonance imaging lesions in nucleus pallidus and putamen. Both children have reached their teenage years, and they are intellectually active, despite their motor problems.

A novel mouse model that recapitulates adult-onset glycogenosis type 4.

Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder caused by deficiency of the glycogen-branching enzyme (GBE). The diagnostic hallmark of the disease is the accumulation of a poorly branched form of glycogen known as polyglucosan (PG). The disease is clinically heterogeneous, with variable tissue involvement and age at onset. Complete loss of enzyme activity is lethal in utero or in infancy and affects primarily the muscle and the liver. However, residual enzyme activity as low as 5-20% leads to juvenile or adult onset of a disorder that primarily affects the central and peripheral nervous system and muscles and in the latter is termed adult polyglucosan body disease (APBD). Here, we describe a mouse model of GSD IV that reflects this spectrum of disease. Homologous recombination was used to knock in the most common GBE1 mutation p.Y329S c.986A > C found in APBD patients of Ashkenazi Jewish decent. Mice homozygous for this allele (Gbe1(ys/ys)) exhibit a phenotype similar to APBD, with widespread accumulation of PG. Adult mice exhibit progressive neuromuscular dysfunction and die prematurely. While the onset of symptoms is limited to adult mice, PG accumulates in tissues of newborn mice but is initially absent from the cerebral cortex and heart muscle. Thus, PG is well tolerated in most tissues, but the eventual accumulation in neurons and their axons causes neuropathy that leads to hind limb spasticity and premature death. This mouse model mimics the pathology and pathophysiologic features of human adult-onset branching enzyme deficiency.

Preservative solution for skeletal muscle biopsy samples.

CONTEXT: Muscle biopsy samples must be frozen with liquid nitrogen immediately after excision and maintained at -80°C until analysis. Because of this requirement for tissue processing, patients with neuromuscular diseases often have to travel to centers with on-site muscle pathology laboratories for muscle biopsy sample excision to ensure that samples are properly preserved. AIM: Here, we developed a preservative solution and examined its protectiveness on striated muscle tissues for a minimum of the length of time that would be required to reach a specific muscle pathology laboratory. MATERIALS AND METHODS: A preservative solution called Kurt-Ozcan (KO) solution was prepared. Eight healthy Sprague-Dawley rats were sacrificed; striated muscle tissue samples were collected and divided into six different groups. Muscle tissue samples were separated into groups for morphological, enzyme histochemical, molecular, and biochemical analysis. STATISTICAL METHOD USED: Chi-square and Kruskal Wallis tests. RESULTS: Samples kept in the KO and University of Wisconsin (UW) solutions exhibited very good morphological scores at 3, 6, and 18 hours, but artificial changes were observed at 24 hours. Similar findings were observed for the evaluated enzyme activities. There were no differences between the control group and the samples kept in the KO or UW solution at 3, 6, and 18 hours for morphological, enzyme histochemical, and biochemical features. The messenger ribonucleic acid (mRNA) of ß-actin gene was protected up to 6 hours in the KO and UW solutions. CONCLUSION: The KO solution protects the morphological, enzyme histochemical, and biochemical features of striated muscle tissue of healthy rats for 18 hours and preserves the mRNA for 6 hours.

Metabolic and Histopathological Effects of Fructose Intake During Pregestation, Gestation and Lactation in Rats and their Offspring.

OBJECTIVE: Studies have demonstrated a significant relationship between maternal fructose intake and metabolic outcome in their offspring. However, there is a paucity of data about the long-term effects of fructose intake on the offspring of fructose-fed dams. Therefore, we planned a study to evaluate the long-term effects of fructose intake on the offspring of dam rats fed a high-fructose diet. METHODS: Sixteen virgin female Sprague-Dawley rats were divided into two groups. Group 1 received a regular diet and Group 2 a high-fructose diet. Both groups received their experimental diets for 8 weeks before conception. They were mated and continued to feed with their experimental diet during mating and during their pregnancy and lactation periods. After weaning, the offspring from each group were divided into two groups. Group 1A received a regular diet, Group 1B - a fructose diet, Group 2A - a regular diet and Group 2B received a fructose diet. After weaning, the offspring were anesthetized and blood samples were collected for biochemical analysis. Liver, kidney and retroperitoneal adipose tissue were harvested for histopathological examination. Primary antibodies against inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined as early inflammation markers. RESULTS: After weaning, while daily water consumption was found to be significantly higher in Groups 2B and 1B (p<0.01), daily laboratory chow consumption was significantly lower in Groups 1A and 2A (p<0.01). Body weight was significantly higher in Groups 1B and 2B (p<0.01). Serum glucose, triglyceride, low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol levels were found to be increased and high-density lipoprotein cholesterol levels decreased in Group 2B (p<0.05). The intensities of iNOS staining in the retroperitoneal adipose tissue, COX-2 staining in the liver and both iNOS and COX-2 staining in the kidney were higher in Group 2B (p<0.05). CONCLUSION: Based on our findings, we believe that the offspring of dams which received a high fructose intake during their pregestation, gestation and lactation periods are at risk of developing metabolic syndrome in their later life only if they continue to receive a high intake of fructose. We therefore propose that the risk of developing metabolic syndrome can probably be reduced by modifying the diet of the offspring after weaning.