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.

Alternative products to treat allergic rhinitis and alternative routes for allergy immunotherapy.

BACKGROUND: Some alternative products instead of immunotherapy are used in patients with allergic rhinitis (AR). METHODS: In this paper, alternative products to treat allergic rhinitis and alternative routes for allergy immunotherapy are reviewed. RESULTS: Alternative products and methods used instead of immunotherapy are tea therapy, acupuncture, Nigella sativa, cinnamon bark, Spanish needle, acerola, capsaicin (Capsicum annum), allergen-absorbing ointment, and cellulose powder. N. sativa has been used in AR treatment due to its anti-inflammatory effects. N. sativa oil also inhibits the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism. The beneficial effects of N. sativa seed supplementation on the symptoms of AR may be due to its antihistaminic properties. To improve the efficacy of immunotherapy, some measures are taken regarding known immunotherapy applications and alternative routes of intralymphatic immunotherapy and epicutaneous immunotherapy are used. CONCLUSION: There are alternative routes and products to improve the efficacy of immunotherapy.

Adrenomedullin predicts high risk and culture positivity in children with solid tumors suffering from neutropenic fever.

AIM OF STUDY: Neutropenic fever is a source of morbidity and mortality in children with cancer. It is not possible to detect the causative agent in cultures in most cases; the research for a marker that can show the severity of the disease is ongoing. We evaluated the role of adrenomedullin (ADM) at predicting prognosis on patients with febrile neutropenia, which has been proven to be a good prognostic marker for diseases with high morbidity and mortality, such as heart failure, ischemic ventricular dysfunction, sepsis, and systemic inflammatory response syndrome. MATERIALS AND METHODS: We recorded the 36 febrile episodes of 14 children receiving chemotherapy due to solid tumors. There were 10 events with unknown origin in the low-risk group, while in the high-risk group, there were 17 events with unknown origin, 8 events with microbiological origin and 1 event with clinically proven infection. Cultures were positive only in the high-risk group. However, the changes of ADM levels through time periods (first, second, third, and seventh days) were not significant. RESULTS: The first-day plasma ADM levels significantly predicted the presence of culture positivity (AUC 0.628, 95% CI 0.40-0.85, p = 0.303) and high-risk patients with neutropenic fever (AUC 0.76, 95% CI 0.56-0.97, p = 0.016). CONCLUSION: Our study showed that increased plasma ADM was correlated with high-risk neutropenic fever and culture positivity. The ADM levels in the high-risk group were clearly high at the diagnosis and continued to the end of the treatment.

NFU1 gene mutation and mitochondrial disorders.

Mitochondrial respiratory chains consist of approximately 100 structural proteins. Thirteen of these structural proteins are encoded by mitochondrial DNA (mtDNA), and the others by nuclear DNA (nDNA). Mutation in any of the mitochondrial structural-protein related genes, regardless of whether they are in the nDNA or mtDNA, might cause mitochondrial disorders. In the recent past, new nuclear genes required for assembly, maintenance, and translation of respiratory chain proteins have been found. Mutation in these genes might also cause mitochondrial disorders (MD). NFU1 gene is one of such genes and has a role in the assembly of iron-sulfur cluster (ISC). ISCs are included in a variety of metalloproteins, such as the ferredoxins, as well as in enzymatic reactions and have been first identified in the oxidation-reduction reactions of mitochondrial electron transport. It is important to be aware of NFU1 gene mutations that may cause severe mitochondrial respiratory chain defects, mitochondrial encephalomyopathies and death, early in life.

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.

Comparison of the efficacy of once- and twice-daily colchicine dosage in pediatric patients with familial Mediterranean fever--a randomized controlled noninferiority trial.

BACKGROUND: In this study, we examined the efficacy and safety of a once-daily dosage schema of colchicine compared with a twice-daily dosage schema in pediatric patients with familial Mediterranean fever (FMF). METHODS: In this 24-week, multicenter, randomized controlled noninferiority trial, pediatric patients newly diagnosed with FMF carrying a homozygous or compound heterozygous mutation and not receiving any treatment were included. Patients were randomly assigned using a block randomization method to receive treatment with a once- or twice-daily dosage. Clinical and laboratory characteristics and medication side effects were recorded and compared between groups. The study was carried out in compliance with Good Clinical Practice and the Consolidated Standards for Reporting of Trials (CONSORT) statement. RESULTS: A total of 92 patients were selected, and 79 patients completed the study. There were 42 patients in the once-daily dosage group and 37 in the twice-daily dosage group. The results indicated that the once-daily dosage was not inferior to the twice-daily dosage regarding decrease in attack frequency and duration as well as improvement in clinical findings and Mor severity scores. Alterations in laboratory findings indicating inflammation, such as erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A, were similar in both groups. The rates of drug side effects were similar between the once- and twice-daily dosage groups, implying comparable safety of colchicine, with the exception of diarrhea, which was slightly higher in the once-daily dosage group. CONCLUSIONS: Using colchicine with either a once- or twice-daily dosage provides similar clinical and laboratory improvements. Considering both efficacy and safety, colchicine can be prescribed with a once-daily dosage. TRIAL REGISTRATION ID: ClinicalTrials.gov identifier NCT02602028 . Registered 5 November 2015.

Possible relationship between amino acids, aggression and psychopathy.

OBJECTIVE: Aggressive behaviour is associated with reduced serotonin metabolism in the brain, but there is not enough knowledge on potential changes of the serotonin precursor levels among violent offenders. In this study, we aimed to evaluate the relationships among the tendency of psychopathy, anger and the basic amino acids. METHODS: Fifty-two young adult male patients with antisocial personality disorder (APD) and 30 healthy men included the study. Serum amino acid levels were measured by HPLC method. Aggression questionnaire and Hare Psychopathology Scale were used for all participants. RESULTS: Blood levels of phosphoserine, aspartic acid, glutamic acid, aminoadipic acid and 1-methylhistidine in group of patients with APD were significantly higher than the control group. Blood levels of TRP, asparagine, citrulline, cystine, isoleucine, tyrosine, histidine, hydroxylysine, lysine, ethanolamine and arginine in the group of patients were found lower than the control group. A significant positive correlation between anger scores and histidine, methionine and GABA was found. GABA and methionine showed a significant correlation with the indirect aggression score. CONCLUSION: Our study showed a relationship between serum amino acid levels and the scores of aggression and psychopathy. We think that this is a productive research area for understanding the relationship among biochemical factors, aggression and psychopathy.

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.

Alternative products to treat allergic rhinitis and alternative routes for allergy immunotherapy.

BACKGROUND: Some alternative products instead of immunotherapy are used in patients with allergic rhinitis (AR). METHODS: In this paper, alternative products to treat allergic rhinitis and alternative routes for allergy immunotherapy are reviewed. RESULTS: Alternative products and methods used instead of immunotherapy are tea therapy, acupuncture, Nigella sativa, cinnamon bark, Spanish needle, acerola, capsaicin (Capsicum annum), allergen-absorbing ointment, and cellulose powder. N. sativa has been used in AR treatment due to its anti-inflammatory effects. N. sativa oil also inhibits the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism. The beneficial effects of N. sativa seed supplementation on the symptoms of AR may be due to its antihistaminic properties. To improve the efficacy of immunotherapy, some measures are taken regarding known immunotherapy applications and alternative routes of intralymphatic immunotherapy and epicutaneous immunotherapy are used. CONCLUSION: There are alternative routes and products to improve the efficacy of immunotherapy.

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.