Factors affecting treatment adherence to atomoxetine in ADHD: a systematic review.

The purpose of this paper was to systematically review the literature related to research about the factors affecting treatment adherence and discontinuation of atomoxetine in pediatric, adolescent, and adult patients with attention-deficit/hyperactivity disorder (ADHD). Medline was systematically searched using the following prespecified terms: "ADHD", "Adherence", "Compliance", "Discontinuation", and "Atomoxetine". We identified 31 articles that met all inclusion and exclusion criteria. The findings from this review indicate that persistence and adherence to atomoxetine treatment were generally high. Factors found to influence adherence and nonadherence to atomoxetine treatment in ADHD in this review include age, sex, the definition of response used, length of treatment, initial dose of treatment, comorbid conditions, and reimbursement. Tolerability was cited as an important reason for treatment discontinuation. More research is needed to understand those factors that can help to identify patients at risk for poor adherence and interventions that could improve treatment adherence early in the stage of this illness to secure a better long-term prognosis.

Patient characteristics associated with treatment initiation among paediatric patients with Attention-Deficit/Hyperactivity Disorder symptoms in a naturalistic setting in Central Europe and East Asia.

BACKGROUND: Cultural views of Attention-Deficit/Hyperactivity Disorder (ADHD), differing healthcare systems and funding mechanisms, and the availability of mental health services can greatly influence the perceptions, diagnosis, and treatment of ADHD. There is, however, lack of information about treatment practice and the treatment decision-making process for ADHD, particularly in non-Western countries. Our study compared characteristics of paediatric patients newly diagnosed with ADHD symptoms who did and who did not initiate treatment, and also examined whether any differences varied by region in Central Europe and East Asia. METHODS: Data were taken from a 1-year prospective, observational study that included 1,068 paediatric patients newly diagnosed with ADHD symptoms. Clinical severity was measured using the Clinical Global Impression-ADHD-Severity (CGI-ADHD-S) scale and the Child Symptom Inventory-4 (CSI-4) checklist. Logistic regression was used to explore patient characteristics associated with treatment initiation (pharmacotherapy and/or psychotherapy) at baseline for each region. RESULTS: A total of 74.3% of patients initiated treatment at baseline (78.3% in Central Europe and 69.9% in East Asia). Of these, 48.8% started with both pharmacotherapy and psychotherapy in Central Europe, and only 17.1% did so in East Asia. The level of clinical severity was highest in the combination treatment group in Central Europe, but was highest in the psychotherapy only group in East Asia. In East Asia, treatment initiation was associated with being older, being male, and having a higher CGI-ADHD-S score. In Central Europe, treatment initiation was associated with parental psychological distress, having a higher CSI-4 score, and not being involved in bullying. CONCLUSIONS: Although factors associated with treatment initiation differed to some extent between Central Europe and East Asia, clinical severity appeared to be one of the most important determinants of treatment initiation in both regions. However, the choice between pharmacotherapy and psychotherapy, either alone or in combination, varied substantially across the regions.

Predictors and consequences of adherence to the treatment of pediatric patients with attention-deficit/hyperactivity disorder in Central Europe and East Asia.

PURPOSE: To assess baseline predictors and consequences of medication non-adherence in the treatment of pediatric patients with attention-deficit/hyperactivity disorder (ADHD) from Central Europe and East Asia. PATIENTS AND METHODS: Data for this post-hoc analysis were taken from a 1-year prospective, observational study that included a total of 1,068 newly-diagnosed pediatric patients with ADHD symptoms from Central Europe and East Asia. Medication adherence during the week prior to each visit was assessed by treating physicians using a 5-point Likert scale, and then dichotomized into either adherent or non-adherent. Clinical severity was measured by the Clinical Global Impressions-ADHD-Severity (CGI-ADHD) scale and the Child Symptom Inventory-4 (CSI-4) Checklist. Health-Related Quality of Life (HRQoL) was measured using the Child Health and Illness Profile-Child Edition (CHIP-CE). Regression analyses were used to assess baseline predictors of overall adherence during follow-up, and the impact of time-varying adherence on subsequent outcomes: response (defined as a decrease of at least 1 point in CGI), changes in CGI-ADHD, CSI-4, and the five dimensions of CHIP-CE. RESULTS: Of the 860 patients analyzed, 64.5% (71.6% in Central Europe and 55.5% in East Asia) were rated as adherent and 35.5% as non-adherent during follow-up. Being from East Asia was found to be a strong predictor of non-adherence. In East Asia, a family history of ADHD and parental emotional distress were associated with non-adherence, while having no other children living at home was associated with non-adherence in Central Europe as well as in the overall sample. Non-adherence was associated with poorer response and less improvement on CGI-ADHD and CSI-4, but not on CHIP-CE. CONCLUSION: Non-adherence to medication is common in the treatment of ADHD, particularly in East Asia. Non-adherence was associated with poorer response and less improvement in clinical severity. A limitation of this study is that medication adherence was assessed by the treating clinician using a single item question.

A systematic review of combination therapy with stimulants and atomoxetine for attention-deficit/hyperactivity disorder, including patient characteristics, treatment strategies, effectiveness, and tolerability.

OBJECTIVE: The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD) given combination therapy, 2) treatment strategies used, 3) efficacy and effectiveness, and 4) safety and tolerability. METHODS: Literature databases (MEDLINE(®), EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, and SciVerse Scopus) were systematically searched using prespecified criteria. Publications describing stimulant and atomoxetine combination therapy in patients with ADHD or healthy volunteers were selected for review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy, or other psychiatric/neurologic diseases that could confound ADHD symptom assessment, or other concomitant medication(s) to treat ADHD symptoms. RESULTS: Of the 16 publications included for review, 14 reported findings from 3 prospective studies (4 publications), 7 retrospective studies, and 3 narrative reviews/medication algorithms of patients with ADHD. The other two publications reported findings from two prospective studies of healthy volunteers. The main reason for prescribing combination therapy was inadequate response to previous treatment. In the studies of patients with ADHD, if reported, 1) most patients were children/adolescents and male, and had a combined ADHD subtype; 2) methylphenidate was most often used in combination with atomoxetine for treatment augmentation or switch; 3) ADHD symptom control was improved in some, but not all, patients; and 4) there were no serious adverse events. CONCLUSIONS: Published evidence of the off-label use of stimulant and atomoxetine combination therapy is limited because of the small number of publications, heterogeneous study designs (there was only one prospective, randomized controlled trial), small sample sizes, and geographic bias. Existing evidence suggests, but does not confirm, that this drug combination may benefit some, but not all, patients who have tried several ADHD medications without success.

Habitual snoring in school-aged children: environmental and biological predictors.

BACKGROUND: Habitual snoring, a prominent symptom of sleep-disordered breathing, is an important indicator for a number of health problems in children. Compared to adults, large epidemiological studies on childhood habitual snoring and associated predisposing factors are extremely scarce. The present study aimed to assess the prevalence and associated factors of habitual snoring among Chinese school-aged children. METHODS: A random sample of 20,152 children aged 5.08 to 11.99 years old participated in a cross-sectional survey, which was conducted in eight cities of China. Parent-administrated questionnaires were used to collect information on children's snoring frequency and the possible correlates. RESULTS: The prevalence of habitual snoring was 12.0% (14.5% for boys vs. 9.5% for girls) in our sampled children. Following factors were associated with an increased risk for habitual snoring: lower family income (adjusted odds ratio [OR] = 1.46), lower father's education (OR = 1.38 and 1.14 for middle school or under and high school of educational level, respectively), breastfeeding duration < 6 months (OR = 1.17), pregnancy maternal smoking (OR = 1.51), obesity (OR = 1.50), overweight (OR = 1.35), several respiratory problems associated with atopy and infection, such as chronic/allergic rhinitis (OR = 1.94), asthma (OR = 1.43), adenotonsillar hypertrophy (OR = 2.17), and chronic otitis media (OR = 1.31), and family history of habitual snoring (OR = 1.70). CONCLUSION: The prevalence of habitual snoring in Chinese children was similar to that observed in other countries. The potential predisposing factors covered socioeconomic characteristics, environmental exposures, chronic health problems, and family susceptibility. Compared to socioeconomic status and family susceptibility, environmental exposures and chronic health problems had greater impact, indicating childhood habitual snoring could be partly prevented by health promotion and environmental intervention.

Risk factors associated with short sleep duration among Chinese school-aged children.

OBJECTIVES: To examine risk factors regarding short sleep duration among Chinese school-aged children. METHODS: A random sample of 20,778 children aged around 5-11years participated in a cross-sectional survey, which was conducted in eight cities of China in 2005. A parent-administered questionnaire was used to collect information on children's sleep duration and possible related factors from eight domains. Short sleep duration was defined as total sleep duration <9h per day. RESULTS: In all, 28.3% of the sampled children slept <9h per day. The multivariate logistic regression identified, after adjusting for demographic and socioeconomic variables, factors associated with short sleep duration: more television viewing during weekdays (OR=1.21, p=0.004), more frequent computer/internet using (OR=1.17, p=0.006), earlier school starting time (OR=1.10, p=0.020), more time on homework during weekdays (OR=1.66, p<0.001) and weekends (OR=1.14, p=0.001), poor bedtime hygiene (e.g., having drinks with caffeine after 6:00PM [OR=1.22, p<0.001], doing exciting activities during bedtime [OR=1.16, p<0.001], and irregular bedtime [OR=1.55, p<0.001]), and shorter sleep duration of parents (mother: OR=1.31, p<0.001 for sleep duration <6h and OR=1.24, p=0.006 for 6-8h; father: OR=1.52, p<0.001 for <6h and OR=1.19, p<0.001 for 6-8h). CONCLUSIONS: Factors associated with sleep duration covered multidimensional domains among school-aged children. Compared to sleep environments and chronic health problems, school schedules, lifestyle patterns, and parents' sleep habits had greater impact on children's sleep duration, indicating the existing chronic sleep loss in school children could be, at least partly, intervened by reducing the use of visual technologies, by changing the school schedules, by improving the sleep hygiene routine, and by regulating parents' sleep habits.

[Effects of chelation therapy with succimer in young rabbits of moderate lead poisoning].

OBJECTIVE: To explore the effect of chelation therapy with succimer (DMSA) in male rabbits of moderate lead poisoning during juvenile stage. METHODS: Twenty-four 45-day-old male New Zealand rabbits were randomly divided into three groups (therapy group, TG; positive control group, PG and negative control group, NG, n=8). The TG and PG were orally exposed to lead acetate (5 mg x kg(-1) x d(-1)) for 6 weeks. Rabbits in TG were orally supplied DMSA 1050 mg/m2 in the first week and 700 mg/m2 in the next two weeks, while the other two groups wren't blood and urinary samples of all rabbits were collected per week. The tissues and organs of all rabbits were collected after 12 weeks. The blood lead levels (BLLs) were determined by atomic absorption spectrometer. The urine lead levels and the lead contents of tissue and organ were determined by inductively coupled plasma-mass spectrometry. Histopathology of tissue and organ was observed by light microscope. RESULTS: Compared with PG, the lead level in the morning urine of TG with DMSA chelating was increased significantly. The level was peaked at (1246.96 +/- 157.91) microg/L on the first day after chelating. While the base line was (40.97 +/- 1.77) microg/L before chelating. Meanwhile, the BLLs were sharply declined from (429.63 +/- 10.82) microg/L to (238.50 +/- 11.82) microg/L. The urine lead levels of TG decreased through the 3-week chelating and 3-week discontinuation. The urine lead levels of these two groups were significantly different (F=2934.35, P<0.01). Compared to each two groups in these three groups, there were significant difference (P<0.01). The authors found the reversion of BLLs in first week after stop chelating. The BLLs of PG presented the slow course of declining in the same time, were (135.50 +/- 7.09) microg/L, very close to the level of TG for (149.88 +/- 11.39) microg/L. Compared with treatment discontinuation for 3 weeks, the urine lead levels and the body weight gain of the therapy group increased more than that of PG, and the BLLs and the lead concentrations in tissues and organs decreased more than that of PG, and histopathology in the liver tissues and testicle tissues were improved. CONCLUSION: DMSA chelating for the rodent models of moderate lead poisoning might reduce the BLLs and soft tissue lead contents quickly and effectively, decrease toxic effects of lead in a short period of time, thus alleviate the impairment of lead poisoning on tissues and organs by decreasing lead burden, and bring out improvement on the growth retardation caused by lead poisoning.

Sleep problems in chinese school-aged children with a parent-reported history of ADHD.

OBJECTIVE: The objective was to survey the prevalence of parent-reported ADHD diagnosis and to assess its associations with sleep problems among urban school-aged children in China. METHOD: A random sample of 20,152 school-aged children participated in a cross-sectional survey in eight cities of China. A parent-administered questionnaire and the Children's Sleep Habits Questionnaire were completed to quantify history of ADHD diagnosis and sleep problems, respectively. RESULTS: Slightly more than 4% of Chinese school-aged children were reported to have a history of ADHD diagnosis. The multivariate regression models revealed that, after controlling for some confounders-such as gender, parents' educational level, family income, family structure, and stimulant medication-there was a higher prevalence of sleep problems, especially parasomnias, sleep-disordered breathing, and daytime sleepiness, in children with a history of ADHD diagnosis. CONCLUSION: The results emphasized the importance of incorporating screens of sleep problems into the evaluation of ADHD.

[Sleep habits and sleep disturbance in school-age children of China].

OBJECTIVE: To survey the sleep habits (bedtime, wake time), sleep duration, and sleep problems in school-age children of China. METHOD: From November to December, 2005, a total of 19,299 school-age children from 55 elementary schools of 9 cities entered the study by a cross-sectional survey. A parent-administered questionnaire and the Chinese version of the Children's Sleep Habits Questionnaire were applied to investigate children's sociodemographic characteristics and sleep behaviors, respectively. RESULTS: The mean sleep duration was 9 hours and 10 minutes (9:10, SD:48 min) during the weekdays and 9:48 (SD: 63 min) during the weekends. In about 71.4% and 41.8% school-aged children the sleep duration per day did not reach the lowest criterion of 10 hours recommended by the Ministry of Education of China during weekdays and weekends, respectively. Sleep problems were common with prevalence ranging from 14.5% for sleep-disordered breathing to 75.3% for daytime sleepiness. Parasomnia (chi(2) = 13.76, P < 0.01) and sleep-disordered breathing (chi(2) = 119.83, P < 0.01) were more prevalent in boys than in girls; however, sleep anxiety was more prevalent in girls than in boys (chi(2) = 19.42, P < 0.01). Except for night waking, other types of sleep problems were significantly associated with age. CONCLUSIONS: Inadequate sleep duration and sleep problems prevail among school-age children, which indicates that children's sleep health may be a major public health concern in China.

[Effects of moderate lead poisoning on the hippocampus tissue of rabbits in juvenile stage].

OBJECTIVE: To understand the effects of moderate lead poisoning on the hippocampus tissue of rabbits in juvenile stage. METHODS: Sixteen 45-day-old male New Zealand rabbits were randomly divided into blank group and lead-exposed group,8 for each group. Rabbits in the lead-exposed group were treated with 5 mg x kg(-1) x d(-1) lead acetate in their forage for 6 weeks to establish a moderate lead poisoning animal model. The blood lead levels and the lead contents in the hippocampus were determined by atomic absorption spectrometer and inductively coupled plasma-mass spectrometry respectively. Histopathology and ultra-microstructure in the hippocampus tissue were observed by light microscope and electron microscope. The NR1, NR2A and NR2B protein expressions in the CA1 hippocampal region were analyzed through immunohistochemical method. RESULTS: Compared with those of blank group, the blood lead levels of lead-exposed group were significant increased, (428.63 +/- 9.46) vs (66.38+/-3.93) microg/L (t = 100.08, P<0.01); and lead contents of hippocampus was significantly increased, (44.57+/-2.03) vs (21.20+/-1.53) ng/g, (t = 26.05, P<0.01); the hippocampus wet weight were significant decreased, (0.735 +/-0.012) vs (0.808+/-0.010), (t =12.97, P<0.01); the coefficient of hippocampus wet weight, was (0.458 +/-0.004) vs (0.476+/-0.005), (t =7.87, P<0.01). The significant declines in both the positive rate of NR1 and NR2A in the CA1 hippocampal region for NR1: (37.44 +/- 2.05)% vs (41.81+/-2.50)% (t = 3.82, P<0.01) and for NR2A: 21.97+/-1.08 vs 25.48+/-1.30 (t =5.89, P<0.01) were also observed. With light microscope and electron microscope, the histopathology and ultra-microstructure of neuron and glial cell in the hippocampus tissue were changed. CONCLUSION: The impairment of hippocampus of rabbits in juvenile stage with chronic moderate lead poisoning were observed, and the histopathology and N-methyl-D-aspartate receptor protein expressions in the hippocampus tissue were changed.

Bed- and room-sharing in Chinese school-aged children: prevalence and association with sleep behaviors.

OBJECTIVE: To survey the prevalence of bed- and room-sharing and assess associations with sleep/wake patterns, duration of sleep, and sleep problems among urban school-aged children in China. METHODS: Students representing eight Chinese cities were studied during November and December, 2005. A total of 19,299 elementary-school children (49.7% boys and 50.3% girls with a mean age of 9.00 years) participated in the survey. A parent-administered questionnaire and the Chinese version of the Children's Sleep Habits Questionnaire were completed to quantify children's sleep arrangements and to characterize sleep behaviors. RESULTS: Co-sleeping was a common practice, with a prevalence of 37.6% (routine bed-sharing: 23.0%; room-sharing: 14.6%) in Chinese school-aged children. Bed- and room-sharing did not show significant gender difference but gradually decreased with increasing age. Compared to room-sharing and sleeping alone, bed-sharing was correlated with later bedtimes, later awakening times, and a shorter duration of sleep. However, the small difference was unlikely to have clinical significance. Bed- and room-sharing tended to be associated with the increased probability of six types of sleep problems: bedtime resistance, sleep anxiety, night waking, parasomnia, sleep-disordered breathing, and daytime sleepiness. Compared to bed-sharing, room-sharing had a lower odds ratio. Among six sleep problems, bedtime resistance and sleep anxiety had the strongest association with bed-sharing. CONCLUSIONS: Sleep problems were common in Chinese school-aged children. Co-sleeping was highly prevalent and may be potentially associated with negative effects on sleep hygiene and sleep quality, although the context of the co-sleeping must be taken into consideration.

Epidemiological study of sleep characteristics in Chinese children 1-23 months of age.

BACKGROUND: Sleep plays a critical role in normal development and the effects of culture upon sleep are especially important in young children. The purpose of the present paper was to determine the sleep times and the prevalence of sleep problems and co-sleeping in children from Shanghai. METHODS: A cross-sectional design incorporating parental self-report was used to investigate the sleep-related habits of 1129 children, 1-23 months of age, randomly selected from the five districts of Shanghai, China. RESULTS: The total sleep time (TST) of Chinese young children was less than that reported in Western populations, and the prevalence of sleep problems (65.97%) was higher than that for Western children. The sleep problems of children were significantly related to perinatal factors and certain behavior problems. The rate of bed sharing did not differ between boys and girls but significantly increased with age from 44.07% in 1-month-olds to 71.51% in 23-month-olds. CONCLUSIONS: Sleep problems that cross cultures result from a variety of behavioral and health problems. Nevertheless, it is speculated that reduced TST in Chinese children may be related to factors unique to China, such as co-sleeping and child-rearing practices.

[Development and psychometric properties of the Chinese version of Children's Sleep Habits Questionnaire].

OBJECTIVE: To develop the Chinese version of Children's Sleep Habits Questionnaire (CSHQ) by translating and retranslating the English version of CSHQ and to examine the reliability, content validity, construct validity of the Chinese version in a general population of school-age children. METHODS: During November and December 2005, a total of 20 457 school-age children from 55 primary schools of 9 cities were recruited through cluster-stratified selection, using geographic location, economic standard, and population density as criteria. A parent-administered questionnaire and the Chinese version of CSHQ were completed to quantify sociodemographic characteristics and to characterize sleep patterns and sleep disturbances, respectively. RESULTS: The internal consistency of overall questionnaire and the eight subscales of the Chinese version of CSHQ was good (Cronbach's alpha coefficient was 0.73 and ranged from 0.42 to 0.69, respectively). The consistency between mother and father was ICCs = 0.89 for overall questionnaire and ranged from ICCs = 0.83 to ICCs = 0.92 for subscales. The test-retest reliability was ICCs = 0.85 for overall questionnaire and range from ICCs = 0.60 to ICCs = 0.88 for subscales. Factor analysis revealed a three-factor structure, which could represent bedtime behavior problems, sleep disturbance, sleep duration and daytime sleepiness, respectively, and the three factors could be used to explain 58.63% of the total variance. The factor loading was above 0.5 for the corresponding subscale. CONCLUSIONS: Reliability, content validity and construct validity of the Chinese version of CSHQ in a general population of school-age children are good. It appears to be a suitable instrument for measuring sleep patterns and screening for sleep problems in school-aged children.

The impact of media use on sleep patterns and sleep disorders among school-aged children in China.

STUDY OBJECTIVES: To determine the amount of television viewing and computer use in urban school-aged Chinese children, and to examine their associations with sleep/wake patterns, duration of sleep, and sleep disorders. DESIGN AND SETTING: Students representing 8 Chinese cities were studied during November and December 2005. PARTICIPANTS: A total of 19,299 elementary-school children, 49.7% boys and 50.3% girls, with a mean age of 9.00 years, participated in the survey. MEASUREMENTS: A parent-administered questionnaire and the Chinese version of the Children's Sleep Habits Questionnaire were completed to quantify media use and to characterize sleep patterns and sleep disturbances. RESULTS: A television or computer was present in the bedroom of 18.5% and 18.3% of Chinese school-aged children, respectively. Media presence in the bedroom and media use were positively correlated with later bedtimes, later awakening times, and a shorter duration of sleep during weekdays and weekends. They were also significantly associated with at least 2 types of sleep disturbances. Overall, the most affected sleep behaviors were bedtime and awakening time on the weekends, the duration of sleep during the weekdays, and sleep disorders of bedtime resistance and sleep anxiety. Television viewing > or = 2 hours/day on weekends, with a prevalence of 48.8%, was the predominant risk factor for all sleep disorders with the exception of the sleep duration disorder. Computer use, however, had no correlation with any sleep disorder. CONCLUSION: The presence of media in a child's bedroom and media use had a negative effect on children's sleep/wake patterns, duration of sleep, and sleep disorders.

Protective effects of insulin on polychlorinated biphenyls-induced disruption of actin cytoskeleton in hippocampal neurons.

Insulin receptors are widely distributed in the brain, and insulin improves learning and memory in some brain injury. Insulin elevates LIM kinase 1 (LIMK-1) activity and induces actin polymerization in some cells, while actin cytoskeleton dynamics mediated via LIMK-1/cofilin signal pathway is considered important to learning and memory formation. Our previous studies have shown that polychlorinated biphenyls (PCBs) disrupt the actin cytoskeleton by inhibiting LIMK-1/cofilin signaling pathway in the cultured hippocampal neurons. To determine potential neuronal protective effects by insulin, we administered insulin to the cultured hippocampal neurons after exposure to PCBs mixture Aroclor 1254 (A 1254). We found that insulin antagonized a loss of filamentous actin and the cytotoxicity induced by A 1254. Similarly, insulin restored the decrease of LIMK-1 and cofilin phosphorylation induced by A 1254. We concluded that insulin could protect neurons, probably partly by ameliorating filamentous actin cytoskeleton disruption mediated via the activation of LIMK-1/cofilin signal pathway in cultured hippocampal neurons after exposure to A 1254. The above protective effects in hippocampal neuron may have important implications in the treatment of PCBs-induced neurotoxicity and the mechanism by which insulin improves learning and memory. (c) 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 152-158, 2007.

Developmental lead exposure alters gene expression of metabotropic glutamate receptors in rat hippocampal neurons.

Exposure to lead in utero and in infancy is associated with a risk of impaired cognitive development. Increasing evidence suggests that the family of metabotropic glutamate receptors (mGluRs) plays an important role in synaptic plasticity and memory formation. We determined whether mGluRs subtypes 1, 3, and 7 (mGluR1, mGluR3, and mGluR7) were involved in developmental neurotoxicity due to lead. Embryonic rat hippocampal neurons were cultured for 21 days and exposed to lead chloride beginning on the fourth day of incubation. We investigated levels of mGluR1, mGluR3, and mGluR7 mRNA expression by using quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) with lead exposure at 10 nM, 1 microM, and 100 microM. Lead exposure in vitro downregulated the expression of mGluR1 mRNA and upregulated the expression of mGluR3 and mGluR7 mRNA in a dose-dependent manner. We speculate that mGluRs may be involved in lead neurotoxicity. Pathways that likely contribute to lead neurotoxicity by means of mGluRs are impairment of long-term potentiation, effects on N-methyl-D-aspartate (NMDA) receptor functions, and depotentiation.

Polychlorinated biphenyls disrupt the actin cytoskeleton in hippocampal neurons.

It is well known that developmental exposure to polychlorinated biphenyls (PCBs) could cause learning and memory deficits, but the underlying mechanisms are not clear. Actin cytoskeleton is directly involved in synaptic plasticity which is considered critical to learning and memory formation by LIM kinase 1 (LIMK-1)/cofilin pathway. To determine whether PCBs could alter actin cytoskeleton, we exposed the cultured hippocampal neurons to PCBs mixture Aroclor 1254 (A 1254). By biochemical measurement, fluorimetric assay and fluorescence microscopy, we found that A 1254 elicited a loss of filamentous actin, which preceded cytotoxicity. Western blots showed that a concentration-dependent decrease in the phosphorylation of cofilin and a decrease in LIMK-1 were induced by A 1254. We concluded that PCBs induced actin depolymerization in hippocampal neurons, probably by inhibiting the LIMK-1/cofilin signaling pathway. The above findings offer new perspectives for the understanding of PCBs-induced learning and memory deficits.

[Effects of perinatal exposure to methylmercury on the structure of hippocampus and cerebellum in young rats].

OBJECTIVE: To evaluate the effects of perinatal exposure to methylmercury on the structure of hippocampus and cerebellum in young pups. METHODS: Divided the 9 pregnant SD rats into three groups randomly: group I, II and III After exposing the rats of the three groups from day 7 in pregnancy through lactation with methylmercury (the dose were 0, 0.1 and 1mg/(kg x d) respectively), examined the early physiology development and the structure of hippocampus and cerebellum of day-21-offspring rats. RESULTS: Except for changes in body weight on 21 day, the offspring showed no apparent changes in appearance and physiology. Pyknosis in several neurons and disturbance arrangement of pyramidal cells in CA3 and CA4 region of the hippocampus were observed in hippocampus and cerebellum of the rats in group III under the microscope, while no pathological changes were observed in group II. Testing the positive expression of immunohistochemistry, we found out that the NF expression of hippocampus in II and III groups were lower than group I (F = 7.94, P < 0.01), while that of GFAP were increased significantly (F = 10.10, P < 0.01). NF expression of cerebellum in group III was lower than group II and group I (F = 6.85, P < 0.05). while that of GFAP was higher than the other two groups (F = 6.85, P < 0.05). The ultrastructure changes happened in both II and III groups examined through electron microscope, including irregular form in nucleus of neurons, pyknosis of soma, degeneration of mitochondria, lysis of dendrite and axon, et al. CONCLUSION: Perinatal low-level methylmercury exposure affected the ultrastructure and expressions of the neural cells in cerebellum and hippocampus of the young rats.

[Association between vitamin D receptor gene polymorphism and vitamin D deficiency rickets].

OBJECTIVE: To explore the genetic susceptibility of children to vitamin D deficiency rickets through studying the association between Vitamin D receptor (VDR) gene polymorphism and vitamin D deficiency rickets. METHODS: One hundred and fifty-nine children (100 boys and 59 girls, aged 0 to 2 years), with new-onset vitamin D deficiency rickets were enrolled. The patients sampled from a community of Jiamusi City, Heilongjiang Province. Seventy-eight healthy age-matched children (46 boys and 32 girls) were used as the controls. VDR gene polymorphism (cleaved by restriction endonuclease Fok I) was analyzed by polymerase chase reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of the VDR genotype and allele were compared between the two groups. RESULTS: The frequencies of FF, Ff and ff genotypes were 37%, 51% and 12% in the Rickets group, and 18%, 55% and 27% in the Control group. A significant difference was found in the frequency distribution of the VDR genotype between the two groups (chi(2)(0.01(2))=9.210, chi(2)=13.3880, P < 0.01). In the Rickets group, f allele frequency was lower (37% vs 54%), while the F allele was more common than the Control group (63% vs 46%). CONCLUSIONS: There is an association between the VDR gene Fok I polymorphism and vitamin D deficiency rickets. The individuals with the F allele are more susceptible to vitamin D deficiency rickets.