Evaluation of the Regulatory Role of Circadian Rhythm Related Long Non-Coding RNAs in ADHD Etiogenesis.

OBJECTIVE: ADHD is associated with increased sleep problems and circadian rhythm disturbances. This study aimed to examine ADHD patients and healthy controls in terms of chronotypic features and expression levels of CLOCK, PER1, lncRNA HULC, lncRNA UCA1. METHOD: Eighty-three children were included (43 ADHD). Conner's Parent Rating Scale-Revised Short Form, Childhood Chronotype Questionnaire, Children's Sleep Disorders Scale were administered. Gene expression levels were studied from peripheral blood. RESULTS: Evening chronotype, sleep initiation/maintenance disorder, sleep-wake transition disorder, excessive sleepiness disorder were higher in the ADHD group compared to the controls in the scales reported by the parents. Expression levels of all examined genes were statistically significantly higher in the ADHD group. There was no significant relationship between genes and sleep parameters in the ADHD group. CONCLUSION: Our study provides the first evidence that lncRNA HULC and lncRNA UCA1 might have a role in the etiology of ADHD.

Anthropometric Analysis of the Orbital Region in Children With Autism Spectrum Disorder and Healthy Controls.

ABSTRACT: It was aimed to examine the orbital region in children with autism spectrum disorder and comparison with the healthy controls in the present study. A total of 195 children and adolescents (101 of them were in the autism group, 94 of them were in healthy group) were evaluated. Anterior view photographs were taken, and endocanthion (en), exocanthion (ex), and pupil were determined bilaterally on the photographs. Outer canthal (ex-ex), intercanthal (ex-en), inner canthal (en-en) and interpupillary distances were measured and intercanthal index [(en-en / ex-ex) × 100] was calculated. There was a statistically significant difference between the groups for males for all parameters, while a statistically significant difference was not observed for females. All orbital region distances were higher in male autistic children. Although minor physical anomalies in children and adolescents with autism have been reported before, anthropometric measurements in individuals with autism may differ between genders. Further studies are needed to investigate the differences between genders in autism spectrum disorder.

Evaluation of peripheral inflammatory markers, serum B12, folate, ferritin levels and clinical correlations in children with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).

AIM: The aim of the current study is to compare serum B12, folate, and ferritin levels and peripheral inflammatory indicators between children with Autism Spectrum Disorders (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and healthy controls (HC) and to evaluate the correlation of those with symptoms. MATERIALS AND METHODS: A total of 203 children were evaluated (ASD = 72; ADHD = 61; HC = 70). Diagnoses of ASD and ADHD were ascertained according to Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL). Control group was chosen among the healthy children who applied to general pediatrics outpatient clinic. Gilliam Autism Rating Scale-2 is used to assess autistic symptoms and Atilla Turgay DSM-IV Based Child and Adolescent Behavior Disorders Screening and Rating Scale is used for ADHD symptoms. RESULTS: Neutrophil levels (p = 0.014) and neutrophil/lymphocyte ratio (NLR) (p = 0.016) were higher in the ADHD and ASD groups compared to HC. Neutrophil values explained 70.1% of the variance across groups while NLR explained a further 29.9% of the variance. NLR significantly correlated with social interaction problems in ASD (r = 0.26, p = 0.04). There were no significant differences between groups in terms of vitamin B12, folate and ferritin levels. CONCLUSION: Our results may support involvement of inflammation in the underlying pathophysiology of neurodevelopmental disorders. However, these parameters should be analyzed in a wider population to clarify the effect on the etiology and symptomatology of neurodevelopmental disorders.

The Plasmodium falciparum-induced anion channel of human erythrocytes is an ATP-release pathway.

Infection with the malaria parasite Plasmodium falciparum induces osmolyte and anion channels in the host erythrocyte membrane involving ATP release and autocrine purinergic signaling. P. falciparum-parasitized but not unstimulated uninfected erythrocytes released ATP in a 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB; 7 microM)-sensitive and serum album (SA; 0.5% w/v)-stimulated manner. Since Plasmodium infection of human erythrocytes induces SA-dependent outwardly (OR) and SA-independent inwardly rectifying (IR) anion conductances, we tested whether the infection-induced OR channels directly generate an ATP release pathway. P. falciparum-parasitized erythrocytes were recorded in whole-cell mode with either Cl(-) or ATP as the only anion in the bath or pipette. In parasitized cells with predominant OR activity, replacement of bath NaCl by Na-ATP (NMDG-Cl pipette solution) shifted the current reversal potential (V (rev)) from -2 +/- 1 to +51 +/- 3 mV (n = 15). In cells with predominant IR activity, in contrast, the same maneuver induced a shift of V (rev) to significantly larger (p < or = 0.05, two-tailed t test) values (from -3 +/- 1 to +66 +/- 8 mV; n = 5) and an almost complete inhibition of outward current. The anion channel blocker NPPB reversibly decreased the ATP-generated OR currents from 1.1 +/- 0.1 nS to 0.2 +/- 0.05 nS and further shifted V (rev) to +87 +/- 7 mV (n = 12). The NPPB-sensitive fraction of the OR reversed at +48 +/- 4 mV suggesting a relative permeability of P (ATP)/P (Cl) approximately 0.01. Together, these data raise the possibility that the OR might be the electrophysiological correlate of an erythrocyte ATP release pathway.

Purinoceptors are involved in the induction of an osmolyte permeability in malaria-infected and oxidized human erythrocytes.

In human erythrocytes, infection by the malaria parasite Plasmodium falciparum or oxidative stress induces a new organic osmolyte and anion permeability. To examine a role for autocrine purinoceptor signaling during this induction process, erythrocytic purinoceptor expression, and ATP release were determined. Furthermore, using pharmacological and genetic approaches the dependence on purinoceptor signaling of osmolyte permeability and Plasmodium development, both in vitro and in vivo, were assessed. Extracellular ATP did not induce an osmolyte permeability in non-infected or non-oxidized erythrocytes. ATP and other purinoceptor agonists increased the induction of osmolyte permeability during infection or oxidation as measured by isosmotic hemolysis and patch-clamp recording. Purinoceptor antagonists and apyrase decreased the induced permeability. The observed pharmacology suggested the involvement of P2Y purinoceptors. Accordingly, human erythrocytes expressed P2Y1 protein. Moreover, P2Y1-deficient mouse erythrocytes exhibited a delayed appearance of the osmolyte permeability during P. berghei infection- or oxidation compared with wild-type erythrocytes. Furthermore, the nonspecific purinoceptor antagonist suramin decreased in vitro growth and DNA/RNA amplification of P. falciparum in human erythrocytes and decreased in vivo growth of P. berghei. P. berghei developed slower in P2Y1-deficient mice in vivo compared with wild-type animals. In conclusion, induction of the osmolyte permeability in Plasmodium-infected erythrocytes involves autocrine purinoceptor signaling.

Permselectivity and pH-dependence of Plasmodium falciparum-induced anion currents in human erythrocytes.

Intraerythrocytic survival of the malaria pathogen Plasmodium falciparum requires delivery of nutrients and disposal of waste products across the host erythrocyte membrane. Recent patch-clamp experiments have demonstrated inwardly and outwardly rectifying anion conductances in infected but not in control erythrocytes. A ClC-2-generated fraction of the inwardly rectifying current is activated by cell swelling and presumably subserves host cell volume regulation. In contrast, the outwardly rectifying current is insensitive to cell volume but allows the passage of lactate and is involved in the transport of nutrients. The present study was performed to characterize the permselectivity and pH sensitivity of the anion conductances using whole-cell recording. The outwardly rectifying and the inwardly rectifying currents exhibited permselectivities of Cl- > or = Br- approximately I- > SCN- and SCN- > I- > Br- > Cl-, respectively, as evident from the reversal potentials recorded under biionic conditions. While the inwardly rectifying current was not affected significantly by alterations of pH between 6.0 and 8.4, the outward rectifier was inhibited strongly by alkalinization to pH > or = 7.8. Fluxes of 14C-lactate and parasite growth were decreased markedly by the increase of bath pH, an effect that may at least in part be due to inhibition of the outward rectifier and subsequently impaired transport across the erythrocyte membrane.

Artemisinin inhibits cation currents in malaria-infected human erythrocytes.

BACKGROUND: Previous patch-clamp studies have demonstrated inwardly and outwardly rectifying anion currents, ClC-2 Cl- currents, and nonselective Ca(++)-permeable cation currents in Plasmodium falciparum-infected human erythrocytes. METHODS: The current work studied the effect of the potent antimalarial drug artemisinin on the P falciparum infection-induced whole cell currents in human erythrocyte. RESULTS: Artemisinin had no significant effect on the outwardly rectifying anion currents but inhibited the cation-selective currents with an apparent half-maximal inhibitory concentration of < or =10 micromol/L. CONCLUSION: Because artemisinin reportedly inhibits the asexual parasite amplification with much higher potency, the antimalarial action of the drug cannot be attributed to the artemisinin effect on the cation currents. However, artemisinin may be used as a pharmacologic tool to dissect different current fractions in P falciparum-infected erythrocytes.

Organic osmolyte permeabilities of the malaria-induced anion conductances in human erythrocytes.

Infection of human erythrocytes with the malaria parasite Plasmodium falciparum induces new permeability pathways (NPPs) in the host cell membrane. Isotopic flux measurements demonstrated that the NPP are permeable to a wide variety of molecules, thus allowing uptake of nutrients and release of waste products. Recent patch-clamp recordings demonstrated the infection-induced up-regulation of an inwardly and an outwardly rectifying Cl(-) conductance. The present experiments have been performed to explore the sensitivity to cell volume and the organic osmolyte permeability of the two conductances. It is shown that the outward rectifier has a high relative lactate permeability (P(lactate)/P(Cl) = 0.4). Sucrose inhibited the outward-rectifier and abolished the infection-induced hemolysis in isosmotic sorbitol solution but had no or little effect on the inward-rectifier. Furosemide and NPPB blocked the outward-rectifying lactate current and the sorbitol hemolysis with IC(50)s in the range of 0.1 and 1 microM, respectively. In contrast, the IC(50)s of NPPB and furosemide for the inward-rectifying current were >10 microM. Osmotic cell-shrinkage inhibited the inwardly but not the outwardly rectifying conductance. In conclusion, the parasite-induced outwardly-rectifying anion conductance allows permeation of lactate and neutral carbohydrates, whereas the inward rectifier seems largely impermeable to organic solutes. All together, these data should help to resolve ongoing controversy regarding the number of unique channels that exist in P. falciparum-infected erythrocytes.