Potential effects of zinc on information processing in boys with attention deficit hyperactivity disorder

PURPOSE: The aims of the present study were to investigate the relationship between plasma zinc levels and amplitudes and latencies of P1, N2, and P3 in parietal and frontal areas in children with ADHD, and to compare these zinc levels and event-related potentials (ERPs) indices with controls. METHODS: 28 boys with ADHD were divided into two groups according to plasma zinc levels: low zinc group (N=13, zinc level <80 microg/dL) and zinc non-deficient group (N=15, zinc level >or=80 microg/dL). ERP indices from parietal and frontal brain regions were recorded in children with ADHD and in 24 normal boys by using an auditory oddball paradigm. Plasma zinc levels were measured by an atomic absorption spectrophotometer. RESULTS: The plasma zinc levels were significantly lower in both ADHD groups (means are 65.8 microg/dL in low zinc group and 89.5 microg/dL in zinc non-deficient group) than controls (mean: 107.8 microg/dL; both p values <0.017). In ADHD compared to controls, the amplitudes of P3 in frontal and parietal regions were significantly lower, and the latency of P3 in parietal region was significantly longer (all p values <0.017). In low zinc ADHD group compared to zinc non-deficient ADHD group, the latencies of N2 in frontal and parietal region were significantly shorter (all p values <0.017). In addition, there was a medium but significant positive correlation between plasma zinc levels and amplitude and latency of frontal N2 wave in ADHD. CONCLUSIONS: These results can suggest that plasma zinc levels might have an effect on information processing in ADHD children, and lower zinc levels seem to affect N2 wave. Since N2 wave changes may reflect a different inhibition process, further studies are warranted to investigate the effect of zinc on inhibitory process in children with ADHD, and in low zinc and non-deficient ADHD groups.     

Effects of vitamin D administration on nociception and spinal cord pro-oxidant and antioxidant markers in a rat model of neuropathic pain

Reactive oxygen species (ROS) are involved in neuropathic pain, a complicated condition after nerve tissue lesion. Vitamin D appears to improve symptoms of pain and exhibits antioxidant properties. We investigated the effects of oral administration of vitamin D₃, the active form of vitamin D, on nociception, the sciatic functional index (SFI), and spinal cord pro-oxidant and antioxidant markers in rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. Vitamin D₃ (500 IU/kg per day) attenuated the CCI-induced decrease in mechanical withdrawal threshold and thermal withdrawal latency (indicators of antinociception) and SFI. The vitamin prevented increased lipid hydroperoxide levels in injured sciatic nerve without change to total antioxidant capacity (TAC). Vitamin D₃ prevented increased lipid hydroperoxide, superoxide anion generation (SAG), and hydrogen peroxide (H₂O₂) levels in the spinal cord, which were found in rats without treatment at 7 and 28 days post-CCI. A significant negative correlation was found between mechanical threshold and SAG and between mechanical threshold and H₂O₂ at day 7. Vitamin D₃ also prevented decreased spinal cord total thiols content. There was an increase in TAC in the spinal cord of vitamin-treated CCI rats, compared to CCI rats without treatment only at 28 days. No significant changes were found in body weight and blood parameters of hepatic and renal function. These findings demonstrated, for first time, that vitamin D modulated pro-oxidant and antioxidant markers in the spinal cord. Since antinociception occurred in parallel with oxidative changes in the spinal cord, the oxidative changes may have contributed to vitamin D-induced antinociception.     

Retrieving of Pups by Neonatally Stressed Mothers

Abstract

In the rat, perinatal food and maternal deprivation provoke long-lasting effects upon the retrieving responses of dams to displaced pups. In the current study, the retrieving latency and the disruption in the body area of pups chosen by the mother to transport them to a new location was investigated on days 4, 8 and 12 postpartum in lactating Wistar rats. Rats, neonatally underfed by daily (12 h) mother-litter separation in an incubator from days 1 to 23 postpartum, exhibited prolonged retrieving latencies and disruption in the body area of young ones chosen by the dam to transport them to the nest. Furthermore, neonatally underfed dams frequently transported pups in a rude manner eliciting sonic distress cries from them compared to control mothers. These findings are possibly relevant to understand the impact of epigenetic influences on offspring brain and physiological maturation partly mediated through maternal care.     

Pathogenesis of equine herpesvirus‐1 infection in the mouse model

Equine herpesvirus‐1 (EHV‐1) is a major equine pathogen causing respiratory diseases, abortions and severe neurological disorders. The basis of neurological disturbances is, as in other organs, infection of endothelial cells, followed by vasculitis, thrombosis and ischaemic damage of the parenchyma. Here, a murine model was used to explore the mechanism of entry to, and spread within the brain, the cell affinity of the agent and the modulating role of the immune defence, which are all factors governing the pathogenesis of the neurological disease. Because controversial views exist about these mechanisms, we undertook a neuropathological study with intranasally infected adult mice. EHV‐1 entered the brain through the olfactory neuroepithelium and along the olfactory nerves, and spread transsynaptically in rostro‐caudal direction, using olfactory and limbic neuronal networks. Exclusively neurons were infected. The cellular immune reaction exerted a restraining effect on virus dissemination. Following nasal infection, the olfactory route was the major pathway for virus entry and dissemination, involvement of the trigeminal nerve in virus spread seems much less probable. In the adult mouse brain EHV‐1 behaves as a typical neurotropic agent, using, similarly to other herpesviruses, the neuronal networks for dissemination. Vasculitis, the predominant type of lesion in natural infection, and endothelial cell positivity for EHV‐1 were detectable only in the lung. Thus, this agent exhibits in the mouse a dual affinity: it is neurotropic in the brain, and endotheliotropic in visceral organs. Consideration of pathogenetic aspects of equine and experimental murine EHV‐1 infections also helps a better understanding of human herpetic brain disease.     

Nociceptive responses to chronic stress of restraint and noxious stimuli in sucrose fed rats

Stress produces analgesia and sucrose ingestion immediately relieves the stress in both the rat and human models, however the effect of sucrose feeding on chronic stress of repeated varying pain is not known. Adult male rats were subjected to a stress regimen of restraint and various degrees of noxious stimuli given repeatedly during 58 h in six sessions with a rest of 32 h. In a 4‐h session, the rats were subjected to the stress of thermal noxious stimulation, pin prick and electrical stimulation of nociceptive afferents (six, one and nine times at intervals of 5 min) in addition to the restraint stress. The effect of this stress on their nociceptive responses was noted as hind paw lick latency, HPL; tail flick latency, TFL; threshold of tail flick, TF; vocalization during stimulus, SV and vocalization after discharge, VA. On the fourth day, the rats received sucrose solution (20 percent orally) ad libitum, which was withdrawn after session IV. During session II–IV in pre‐sucrose fed state, the TFL remained unaffected as compared to session I, while the HPL decreased (18.53 ± 4.96 s, 12.01 ± 4.64 s in sessions I, VI respectively); and the thresholds for TF, SV and VA (0.34 ± 0.16 and 0.71 ± 0.32 mA in session I, VI respectively) progressively increased. After sucrose ingestion during sessions II–IV, the above‐mentioned decrease in HPL and increase in thresholds was not observed. However, they appeared after discontinuation of sucrose during sessions V and VI. The results of our experiment suggest that exposure to our novel model of chronic (58 h) albeit intermittent stress of noxious stimuli and restraint produced an analgesic response in the threshold of TF, SV and VA, an hyperalgesic response in HPL and no effect in TFL; which were attenuated by ingesting a palatable sucrose solution ad libitum. Copyright © 2001 John Wiley & Sons, Ltd.     

Effects of Chlorine and Its Cresylate Byproducts on Brain and Lung Performance

Chlorine and potassium cresylate spilled from a train wreck forced evacuation of nearly 1,000 people in and near the town of Alberton, Montana, in 1996. Because respiratory and other symptoms persisted in this population, neurobehavioral and pulmonary functions were evaluated in a cohort of exposed vs. unexposed individuals. Ninety-seven subjects were tested 7 wk after exposure. Three years later, 36 of the original subjects were retested, along with 21 new patients exposed in the same incident. These 57 were compared with 22 unexposed individuals. Twenty-six neurobehavioral functions were tested, and spirometry was performed on each subject. At 7 wk postexposure, patients showed significant differences in 5 neurobehavioral functions (i.e., balance, simple reaction time, abnormal visual quadrants, vocabulary, and information), compared with the unexposed individuals recruited in 1999. Patients' Profile of Mood States scores and frequencies of 35 symptoms were also elevated, compared with the unexposed group. At 3 yr postexposure, patients exhibited differences in 7 additional neurobehavioral functions (i.e., choice reaction time, balance with eyes open, color errors, visual fields, Culture Fair, and verbal recall). Respiratory symptoms were increased, but pulmonary functions did not change. Exposure to chlorine and potassium cresylate produced neurobehavioral impairments that have been observed to increase across 3 yr. Spills in heavily populated areas could injure thousands, overwhelming medical facilities.     

Single-trial P3 amplitude and latency informed event-related fMRI models yield different BOLD response patterns to a target detection task

Using single-trial parameters as a regressor in the General Linear Model (GLM) is becoming an increasingly popular method for informing fMRI analysis. However, the parameter used to characterise or to differentiate brain regions involved in the response to a particular task varies across studies (e.g. ERP amplitude, ERP latency, reaction time). Furthermore, the way in which the single-trial information is used in the fMRI analysis is also important. For example, the single-trial parameters can be used as regressors in the GLM or to modify the duration of the events modelled in the GLM. The aim of this study was to investigate the BOLD response to a target detection task when including P3 amplitude, P3 latency and reaction time parameters in the GLM. Simultaneous EEG-fMRI was recorded from fifteen subjects in response to a visual choice reaction time task. Including P3 amplitude as a regressor in the GLM yielded activation in left central opercular cortex, left postcentral gyrus, left insula, left middle frontal gyrus, left insula and left parietal operculum. Using P3 latency and reaction time as an additional regressor yielded no additional activation in comparison with the conventional fMRI analysis. However, when P3 latency or reaction time was used to determine the duration of events at a single-trial level, additional activation was observed in the left postcentral gyrus, left precentral gyrus, anterior cingulate cortex and supramarginal gyrus. Our findings suggest that ERP amplitudes and latencies can yield different activation patterns when used to modify relevant aspects of the GLM.     

The partial positive allosteric GABAA receptor modulator EVT 201 is efficacious and safe in the treatment of adult primary insomnia patients

Objective: To evaluate polysomnographic (PSG) and self-reported measures of the efficacy and safety of EVT 201 in patients with primary insomnia.Patients and methods: Following clinical and PSG screening, 75 patients (mean age: 45.1 ± 11.2y; 50f, 25m) meeting DSM-IV criteria for primary insomnia entered this crossover study and were randomly assigned to double-blind treatment sequences of 1.5 mg or 2.5 mg EVT 201, or placebo using a balanced Latin square design. For each study condition study medication was administered on two consecutive nights and PSG and self-reported data were collected. Safety assessments included physical examination, clinical laboratory measures, electrocardiogram, documentation of adverse events, and the digit symbol substitution test (DSST) and self-reported sleepiness/alertness ratings to detect residual sedation. Data were collected at five US sleep laboratories. Efficacy analyses were performed for the 67 patients completing the study. Safety analyses included all 75 randomized patients.Results: On PSG measures compared to placebo, EVT 201 1.5 mg and 2.5 mg increased total sleep time (TST; 33.1, 45.0 min; both p < 0.0001), reduced wake after sleep onset (WASO; −16.7, −25.7 min; both p < 0.0001), reduced latency to persistent sleep (LPS; −17.0, −20.7 min; both p < 0.0001), and reduced the number of awakenings (−1.2, −2.6; both p < 0.0001). Significant reduction of wake time was seen with 1.5 mg during each of the first three quarters of the night (p < 0.0001–0.002), and with 2.5 mg in all four quarters (p < 0.0001–0.0005). Both doses also improved all key self-reported measures of sleep including total sleep time (rTST; 51.9, 51.1 min; both p < 0.0001), wake after sleep onset (rWASO; −29.3, −29.6 min; both p < 0.0001), sleep latency (rSL; −24.0 min, p < 0.004; −25.1 min, p < 0.0002), and number of awakenings (rNAW; −1.1, −1.2; both p < 0.0001). Sleep quality was also improved by both doses. Self-rated sleepiness in the morning did not differ from placebo for either dose; however, there was a small negative effect on the DSST for both doses. Both doses had similar effects on sleep architecture including an increase in Stage 2 sleep and REM latency and a small, but significant decrease in REM (REM −5.7, −8.3 min; p = 0.0175, p = 0.0006). No effect on other sleep architecture parameters, including SWS, was seen. EVT 201 was well tolerated. No serious or unexpected adverse events were reported.Conclusion: This first study of EVT 201 in adult patients with primary insomnia demonstrated improved measures of sleep onset and sleep maintenance, including during the third and fourth quarters of the night. Adverse events were infrequent and all were mild to moderate in severity.     

弱视儿童治疗前后图型视诱发电位的改变

对14例28只眼功能性弱视儿童治疗前后图型视诱发电位进行了观察。治疗前28只眼的视诱发电位与视力正常儿童的视诱发电位比较,前者有N_1、P_2、N_2各波潜伏期延迟、波幅降低,治疗后潜伏期无明显变化,波幅明显增高(P<0.05),有统计学意义。     

Clinical usefulness of cognitive evoked potentials to assess cognitive deficits in cerebrovascular diseases

Background: The aim of the present study is to evaluate the clinical applicability and usefulness of cognitive evoked potentials (CEP) to identify a cognitive deficit in patients with cerebrovascular diseases (CVD). Methods: The P3 latencies, amplitudes and latency to amplitude ratios (LAR) of CEP were measured in 25 healthy control subjects and 35 inpatients with CVD. The association of CEP with variables including age, sex, mini‐mental state examination (MMSE) score, CVD types, loci of hemiplegic limbs, duration, education, brief psychiatric rating scale (BPRS), instrumental activities of daily living (IADL) and daily living function assessment (DLFA) was also analyzed. Results: (i) The P3 latencies (447.87 ± 113.06 msec) and LAR (65.83 ± 43.25) were prolonged in CVD (P < 0.05), while the amplitudes (8.18 ± 2.51 µV ) were not changed; (ii) the P3 latencies (537.31 ± 101.14msec) and LAR (94.89 ± 46.44 in CVD with a MMSE score <24 were prolonged, and the amplitudes (6.45 ± 1.98 µV ) were reduced (P < 0.05, respectively); (iii) the BPRS, IADL and DLFA in CVD with a MMSE score <24 were different from MMSE ≥24 (P < 0.05); (iv) there was no difference in CEP between CVD caused by infaction and hemorrhage; (v) the P3 latencies were correlated positively with age, BPRS and IADL, while negatively with MMSE and DLFA. The amplitudes were correlated positively with MMSE and DLFA, while negatively with age, BPRS and IADL. The LAR were correlated positively with age, BPRS and IADL, while negatively with MMSE and DLFA; and (vi) on analyzing association of CEP with variables in CVD with MMSE <24, the P3 latencies were correlated positively with BPRS and DLFA, while negatively with MMSE and DLFA. The amplitudes were positively correlated with age. The LAR were positively correlated with IADL. Conclusions: The P3 latencies and LAR of CEP seemed to be useful clinical measures to assess cognitive disorders in CVD as well as in vascular dementia.