Clinical features and subjective/physiological responses to emotional stimuli in the presence of emotion dysregulation in attention-deficit hyperactivity disorder.

INTRODUCTION: Emotion dysregulation (ED) has long been recognized in clinical descriptions of attention-deficit hyperactivity disorder (ADHD), but a renewed interest in ED has advanced research on the overlap between the two entities. Autonomic reactivity (AR) is a neurobiological correlate of emotion regulation; however, the association between ADHD and AR remains unclear. Our aim was to explore the clinical differences, AR, and subjective emotional responses to visual emotional stimuli in ADHD children with and without ED. METHOD: School-aged ADHD children with (n = 28) and without (n = 20) ED, according to the definition of deficiency in emotional self-regulation (DESR), and healthy controls (n = 22) were interviewed by using the Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime version (K-SADS-PL) to screen frequent psychopathologies for these ages. All subjects were evaluated with Child Behavior Checklist 6-18 (CBCL), the Strengths and Difficulties Questionnaire (SDQ), the McMaster Family Assessment Device (FAD), the School-Age Temperament Inventory (SATI), and Conners' Parent Rating Scale (CPRS-48), which were completed by parents. To evaluate emotional responses, the International Affective Picture System (IAPS) and the subjective and physiological responses (electrodermal activity and heart rate reactivity) to selected pictures were examined. RESULTS: Regarding clinically distinctive features, the ADHD+ED group differed from the ADHD-ED and the control groups in terms of having higher temperamental negative reactivity, more oppositional/conduct problems, and lower prosocial behaviors. In the AR measures, children in the ADHD+ED group rated unpleasant stimuli as more negative, but they still had lower heart rate reactivity (HRR) than the ADHD-ED and control groups; moreover, unlike the two other groups, the ADHD+ED group showed no differences in HRR between different emotional stimuli. CONCLUSION: The presented findings are unique in terms of their ability to clinically and physiologically differentiate between ADHD children with and without ED.

Does hypercholesterolemia affect the relaxation of the detrusor smooth muscle in rats? In vitro and in vivo studies.

To evaluate the effects of hypercholesterolemia on the relaxation function of the urinary bladder, we examined the physiological mechanisms involved in the isoproterenol-induced relaxation in isolated detrusor strips in vitro and voiding behavior in vivo in rats. Adult male Sprague-Dawley rats were fed standard (control, N = 16) or 4 % cholesterol diet (hypercholesterolemia, N = 17) for 4 weeks. Concentration-response curves for isoproterenol-induced relaxations in carbachol-precontracted detrusor muscle strips were recorded. The contributions of ß2- and ß3-adrenoceptors and ATP-dependent and Ca(2+)-dependent potassium channels to the relaxation response were investigated by using selective adrenergic agonists salbutamol and BRL 37344 and specific potassium channel inhibitors glibenclamide and charybdotoxin, respectively. Cystometrography was performed to assess bladder function. Hypercholesterolemic rats had higher serum cholesterol and low- and high-density lipoprotein levels than the controls with no sign of atherosclerosis. Isoproterenol-induced relaxation was significantly enhanced in the hypercholesterolemia group. Preincubation with the M2 receptor antagonist attenuated the relaxation response in both groups. The relaxation responses to isoproterenol and salbutamol were similar in both groups, while BRL 37344 appeared to produce a greater relaxant effect in the hypercholesterolemic rats. Also, the inhibitory effects of potassium channel inhibitors on relaxation responses were comparable among the groups. The cystometric findings revealed that threshold and basal pressure values were higher in the hypercholesterolemia group compared with controls. We showed that hypercholesterolemia leads to greater relaxation responses to isoproterenol, appears to impair the braking function of M2 cholinergic receptors on adrenoceptor-induced relaxations in the isolated detrusor muscle, and affects the voiding function in rats.

Effect of transient maternal hypotension on apoptotic cell death in foetal rat brain.

BACKGROUND: Intrauterine perfusion insufficiency induced by transient maternal hypotension has been reported to be associated with foetal brain malformations. However, the effects of maternal hypotension on apoptotic processes in the foetal brain have not been investigated experimentally during the intrauterine period. AIMS: The aim of this study was to investigate the effects of transient maternal hypotension on apoptotic cell death in the intrauterine foetal brain. STUDY DESIGN: Animal experimentation. METHODS: Three-month-old female Wistar albino rats were allocated into four groups (n=5 each). The impact of hypoxic/ischemic injury induced by transient maternal hypotension on the 15th day of pregnancy (late gestation) in rats was investigated at 48 (H17 group) or 96 hours (H19 group) after the insult. Control groups underwent the same procedure except for induction of hypotension (C17 and H17 groups). Brain sections of one randomly selected foetus from each pregnant rat were histopathologically evaluated for hypoxic/ischemic injury in the metencephalon, diencephalon, and telencephalon by terminal transferase-mediated dUTP nick end labelling and active cysteine-dependent aspartate-directed protease-3 (caspase-3) positivity for cell death. RESULTS: The number of terminal transferase-mediated dUTP nick end labelling (+) cells in all the areas examined was comparable in both hypotension and control groups. The H17 group had active caspase-3 (+) cells in the metencephalon and telencephalon, sparing diencephalon, whereas the C19 and H19 groups had active caspase-3 (+) cells in all three regions. The number of active caspase-3 (+) cells in the telencephalon in the H19 group was higher compared with the metencephalon and diencephalon and compared with H17 group (p<0.05). CONCLUSION: Our results suggest that prenatal hypoxic/ischemic injury triggers apoptotic mechanisms. Therefore, blockade of apoptotic pathways, considering the time pattern of the insult, may constitute a potential neuroprotective approach for the detrimental effects of prenatal hypoperfusion.

Evaluation of apoptotic cell death following transient maternal hypotension in fetal rat brain: temporal pattern within the first 24 h after procedure.

BACKGROUND/AIM: To explore the effects of maternal transient systemic hypotension on apoptotic neuronal death in an intrauterine fetal rat brain during the first 24 h after induction of hypotension. MATERIALS AND METHODS: A total of 40 pregnant Sprague-Dawley rats were subjected to either transient systemic hypotension produced for 30 min by blood withdrawal via femoral artery catheterization (hypotension group) or sham operation (control group) on day 15. Two randomly selected fetuses were taken from each rat at 0, 6, 12, and 24 h after the procedure. Apoptosis was evaluated in sections from the whole fetal brain by TUNEL and caspase-3 staining. RESULTS: TUNEL (+) and caspase (+) cells were detected only on the walls of the ventricles of both groups and more abundantly in the hypotension groups than in the control groups at all time points (P <0.05). The increase in TUNEL (+) and caspase (+) cells was highest at 12 h (P < 0.05) following hypotension compared to the other hypotension groups. CONCLUSION: Maternal transient systemic hypotension caused the hypoxia-ischemia (HI)-induced death of immature neurons by apoptosis, and this is especially prominent at 12 h after the insult. Determination of the susceptibility of a developing brain to HI at a certain time may have potential significance on the timing of neuroprotective measures.

The effect of hypercholesterolemia on carbachol-induced contractions of the detrusor smooth muscle in rats: increased role of L-type Ca2+ channels.

To investigate a possible relation between hypercholesterolemia and detrusor smooth muscle function, we studied the contractile response to potassium challenge, carbachol (CCh), and the components of CCh-induced contractile mechanism in high-cholesterol diet-fed rats. Adult male Sprague-Dawley rats were fed with standard (control group, N = 17) or 4 % cholesterol diet (hypercholesterolemia group (HC), N = 16) for 4 weeks. Spontaneous contractions of detrusor muscle strips and their responses to potassium chloride (KCl) or cumulative dose-contraction curves to CCh were recorded. The effects of muscarinic receptor antagonists (methoctramin and/or 4-diphenylacetoxy-N-methylpiperidine), L-type Ca(+2) channel blocker (nifedipine), and/or rho-kinase inhibitor Y-27632 were investigated. Blood cholesterol level was increased in the HC group with no sign of atherosclerosis. The KCl-induced detrusor smooth muscle contractions were higher in HC, whereas spontaneous and CCh-induced responses were similar in both groups. Preincubation with receptor antagonist for M(3) but not for M(2) attenuated contraction significantly, shifting the dose-response curve to the right. This response was similar in both groups. Among two effector mechanisms of M(3)-mediated detrusor smooth muscle contraction, rho-kinase pathway was not affected by hypercholesterolemia, whereas blockade of L-type Ca(+2) channels potently reduced contractions. The results of this study point out a relation between hypercholesterolemia and contractile mechanism of detrusor smooth muscle likely to change urinary bladder function, via altering L-type Ca(+2) channels. Taken together with escalating incidence of hypercholesterolemia and lower urinary tract symptoms, it is a field which deserves to be investigated further.

Effect of gender and menstrual cycle on immune system response to acute mental stress: apoptosis as a mediator.

BACKGROUND/AIMS: We aimed to explore the immunological outcomes of short-term mental stress in apoptosis in peripheral lymphocytes and variations by gender and hormonal status of the individuals together with possible mediators of this interaction. METHODS: Acute mental stress (computerized Stroop color-word interference and cold pressor tests) was applied to men (n = 17) and women (n = 16, in both follicular and luteal phases). Heart rate and blood pressure were monitored throughout the test and after the test until baseline values were recorded. Blood samples were drawn for measuring cortisol and nitric oxide (NO) levels and flow-cytometric cell counting before and after the test. RESULTS: Activation of the stress system was ascertained by increased heart rate, blood pressure and serum cortisol levels after the test. Relative to baseline values, acute mental stress altered the distribution of T and natural killer cells. There was a significant decrease in T helper/T cytotoxic-suppressor cell ratio and an increase in apoptotic T helper cell percentage irrespective of gender or menstrual cycle phase. An increased number of natural killer cells was detected in women, whereas it was decreased in men. After stress induction, serum NO levels remained the same in women and increased in men. Although a correlation was not found between immune system changes and NO levels, glucocorticoids seem to have a role in the observed differences. CONCLUSION: Acute mental stress triggers apoptotic T helper cell loss which was associated with stress system activation, and sex steroids affect the pattern of stress-related immune cell distribution.

Microscopic hematuria as a marker of blunt abdominal trauma in rats: description of an experimental model.

BACKGROUND: Microscopic hematuria is an extremely important sign in blunt abdominal trauma (BAT) patients. Controversies still exist in the literature on whether microscopic hematuria is a sign of intra-abdominal extrarenal organ injury and is an indication for radiographic assessment of BAT patients. In this study, a new BAT rat model was developed, and we tried to determine the relationships between microscopic hematuria and extrarenal intra-abdominal organ injury. METHODS: After verifying our model, lethal and maximal sublethal intensity of impact energy determined in the rats. Animals allocated into six sublethal impact energy groups. BAT was induced by dropping a standard mass from variable heights. After 2 hours of examining period, macroscopic laparotomy findings, histopathological liver, spleen and renal injury grades, and microscopic hematuria levels were recorded in these six groups. RESULTS: According to our results, while the trauma intensity increase severity of the histopathological injury increases for all organs. Although there was a significant correlation between microscopic hematuria and trauma intensity, we could not show same relationship between microscopic hematuria and histopathological organ injury. On the other hand, microscopic hematuria was correlated with the macroscopic laparotomy findings. CONCLUSIONS: Microscopic hematuria could serve as a predictor of the severity of trauma and intra-abdominal organ injury. This study would support the use of abdominal imaging and attentive assessment for intra-abdominal organ injury in stable BAT patients with hematuria. The laparotomy threshold may be lowered for unstable BAT patients with hematuria.

The effects of transient systemic hypotension on renal oxidative status, morphology and plasma nitric oxide levels in pregnant rats.

OBJECTIVE: Transient hypotension attacks, frequently experienced during pregnancy, have detrimental effects on maternal and fetal physiology. Despite the strong autoregulatory mechanisms, kidneys are remarkably sensitive to hypoperfusion. Transient hypotension together with high metabolic demand and increased oxygen requirement during pregnancy may disturb the oxidant status and natural course of nitric oxide (NO) metabolism. Therefore, we investigated in this study the effects of systemic hypotension during pregnancy on kidney oxidant status and morphology and plasma NO levels in an experimental hypotension model in rats. METHODS: Twenty-four rats were allocated into four groups as non-pregnant control (NPC), non-pregnant hypotensive (NPH), pregnant control (PC) and pregnant-hypotensive (PH). Blood pressure was monitored only (NPC, PC) or systemic hypotension by blood withdrawal (NPH, PH) was produced for 30 min following catheterisation on the 15th day of pregnancy or at a corresponding time in the control animals. Animals were sacrificed after 48 h of reperfusion. Malonyldialdehyde (MDA) and reduced glutathione (GSH) levels, superoxide dismutase and catalase activities in the kidneys and plasma NO levels were measured. Tissues were evaluated, histologically. RESULTS: Hypotension and/or pregnancy elevated MDA levels, which was significant in the NPH and PH groups (p < 0.05). GSH levels were lower in all groups compared with the NPC group (p < 0.05). Pregnancy itself increased NO only in the control animals (p < 0.05), not in the hypotensive pregnant rats. Transient hypotension resulted in kidney damage in both hypotension groups, and damage was more prominent in renal cortical regions. The most severe effects were seen in the PH group (p < 0.05). CONCLUSIONS: The findings of this study show that transient hypotension induces a kidney injury in pregnant rats. MDA and GSH in kidneys seem to play a role in the pathophysiology of this injury. However, the roles of antioxidant enzymes and NO and the other underlying mechanisms deserve and necessitate further investigation regarding the long-term health of the mother and fetus.

Vitamin E protects against lipid peroxidation due to cold-SO2 coexposure in mouse lung.

Exposure to sulfur dioxide (SO2) and cold increases especially in the winter. SO2 or cold exposure destroys the oxidant/antioxidant balance and increases lipid peroxidation. However, the effect of coexistence of both factors has not been studied yet. Therefore, we investigated the effect of SO2 and/or repeated short-term cold exposure on the oxidant-antioxidant status and the possible protective role of vitamin E in the cardiopulmonary tissues of mice. Swiss albino mice of both sexes were assigned to eight groups. Four groups were kept at room temperature, injected either with saline or vitamin E (100 mg/kg) in the presence or absence of SO2 exposure (10 ppm, 1 h/day, 30 days). The remaining four groups received the same protocol but were exposed to cold (4 +/- 1 degrees C, 1 h/days, 30 days) instead of room temperature. On day 30, the lung and heart tissues were removed for biochemical analysis. SO2 and cold coexposure increased lactate level in the lung, and elevated thiobarbituric acid-reactive substance (TBARS) and reduced glutathione levels in both tissues, while vitamin E treatment reversed TBARS increment predominantly in the lung. In conclusion, cold and SO2 coexposure exerts more deleterious effects in the cardiopulmonary tissues, while vitamin E treatment seems to be protective, particularly in the lung.