Effect of short-term administration of lead to pregnant rats.

Lead was administred to adult female rats in drinking water (0;0.1:1 and 10 ppm) for 3 weeks before mating, during pregnancy and during 3 weeks after delivery. On day 21 after delivery the mothers and their newborns were sacrified and various parameters of blood -- lead concentration on (Pb-B), hematocrit (Htc), hemoglobin (Hb), free erythrocyte porphyrins (FEP), delta0aminolevulinate dehydratase (ALAD) -- and tissue -- ALAD, free tissue porphyrins (FTP), lead concentration (Pb-T) -- were determined. In mothers a significant increase in Pb-B and Pb concentration in kidney was found in the 10 ppm group, but this increase in lead concentration was not associated with any statistically significant modification of the biochemical parameters. In newborns, lead concentration in blood and in kidney was also significantly increased in the 10 ppm group and this lead exposure was associated with a decrease of the ALAD activity in blood and an increase of FTP in kidney. On the basis of the biochemical parameters investigated one can therefore conclude that the developing organism is more susceptible to the biological action of lead than the organism of adult animals and that the "no-effect" level of lead administered during pregnancy and in the neonatal period is around 1 ppm.     

Disassociation of carbon disulfide-induced depression of flash-evoked potential peak N166 amplitude and norepinephrine levels.

Exposure to organic solvents frequently causes functional impairment of the central nervous system (CNS). One method to examine the effects of solvent exposure on visual function is flash-evoked potentials (FEPs). Greater knowledge of the role of various neurotransmitters in generating FEP peaks would be beneficial for understanding the basis of neurotoxicant-induced changes. FEP peak N166 is influenced by the psychological construct of arousal, which in turn is believed to be influenced by the function of neurons containing norepinephrine (NE). Because of its known effects on both NE and FEPs, we utilized carbon disulfide (CS2) as a means to examine the possible role of NE in modulating the amplitude of FEP peaks N36 and N166. Our hypothesis was that CS2-induced alterations in cortical NE levels would be correlated with changes in FEP peak N36 and N166 amplitudes. Adult male Long-Evans rats were implanted with electrodes over their visual cortex and allowed to recover. To develop peak N166, FEPs were recorded for two days prior to dosing. On the third day, FEPs were recorded prior to dosing, and one group of animals was sacrificed to serve as pretreatment controls. The remaining animals were dosed ip with 0 (corn oil vehicle; 2 ml/kg), 100, 200, or 400 mg/kg CS2. The treated animals were retested at 1, 4, 8, or 24 h after dosing, immediately sacrificed, and samples of the cortex, cerebellum, striatum, and brain stem were frozen for high performance liquid chromatography (HPLC) analysis of monoamine levels. Treatment with CS2 decreased peak N166 amplitude at 1 h, and peak N36 amplitude was depressed at 4 h, relative to the subject's pretreatment values. Peak latencies were increased, and colonic temperature was decreased by treatment with CS2. Exposure to CS2 depressed NE levels in the cortex, brain stem, and cerebellum 4 h after treatment. Conversely, at 4 h, levels of dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid were increased in the brain stem and cerebellum, and levels of the DA metabolite homovanillic acid were increased in the brain stem. Levels of serotonin were unaffected by CS2 treatment. There was a slight increase in striatal levels of the serotonin metabolite 5-hydroxyindole acetic acid at all times after treatment with CS2. There was no apparent association between the decreases in NE levels and the reductions in amplitudes for peaks N36 and N166. The neurochemical mechanism for CS2-induced reductions in FEP peak amplitudes remains to be determined.     

A Study in First-Episode Psychosis Patients: Does Angiotensin I-Converting Enzyme Activity Associated With Genotype Predict Symptom Severity Reductions After Treatment With Atypical Antipsychotic Risperidone?

BackgroundOur previous studies showed increased angiotensin I-converting enzyme (ACE) activity in chronic schizophrenia patients compared with healthy control (HC) volunteers, and the relevance of combining ACE genotype and activity for predicting schizophrenia was suggested.MethodsACE activity was measured in plasma of ACE insertion/deletion (I/D) genotyped HC volunteers (n = 53) and antipsychotic-naïve first-episode psychosis (FEP) patients (n = 45) assessed at baseline (FEB-B) and also after 2 months (FEP-2M) of treatment with the atypical antipsychotic risperidone.ResultsACE activity measurements showed significant differences among HC, FEP-B, and FEP-2M groups (F = 5.356, df = 2, P = .005) as well as between HC and FEP-2M (post-hoc Tukey’s multiple comparisons test, P = .004). No correlation was observed for ACE activity increases and symptom severity reductions in FEP as assessed by total Positive and Negative Syndrome Scale (r = −0.131, P = .434). FEP subgrouped by ACE I/D genotype showed significant ACE activity increases, mainly in the DD genotype subgroup. No correlation between ACE activity and age was observed in FEP or HC groups separately (r = 0.210, P = .392), but ACE activity level differences observed between these groups were influenced by age.ConclusionsThe importance of measuring the ACE activity in blood plasma, associated with ACE I/D genotyping to support the follow-up of FEP patients, did not show correlation with general symptom amelioration in the present study. However, new insights into the influence of age and I/D genotype for ACE activity changes in FEP individuals upon treatment was demonstrated.     

胰腺癌放射治疗辅助高能聚焦超声的临床观察

目的探讨不能手术切除的晚期胰腺癌放射治疗辅助高能聚焦超声治疗的疗效及价值。方法2001年3月～2006年12月我科共收治16例不能切除的晚期胰腺癌患者行放射治疗并辅助高能聚焦超声治疗。按TNM分期，Ⅱ期5例，Ⅲ期6例，Ⅳ期5例。KPS评分30～70分。采用常规分割（1．8～2．0Gy／次，每周5次），放射治疗剂量70～72Gy，所有患者都行6次高能聚焦超声治疗。结果放疗止痛有效率85、7％，全组中位生存期9．2个月（3～30个月），1年生存率31．25％。KPS评分及TNM分期影响生存，KPS60～70分组生存期明显长于KPS30～50分组（P〈0．01），Ⅱ、Ⅲ期患者生存期明显长于Ⅳ期（P〈0．01）。结论对不能切除的局部晚期胰腺癌采用放射治疗并辅助高能聚焦超声可有效缓解症状，改善生存质量，适当延长生存期。     

红细胞游离原卟啉与锌卟啉对铅中毒临床诊断价值的研究

对72例轻度铅中毒、44例铅吸收及7例接触铅无铅中毒住院患者测定了PbB，CPbU(驱铅治疗第一日的尿排铅量)、ALAU、FEP，ZPP。微机分析结果指出不同病情的3组病例之间，5项指标都有极显著的差异，并高度相关，可以相互换算。相关分析表明曲线回归优于直线回归。FEP的升高程度大于ZPP。FEP与ZPP的优点是在慢性铅中毒很少出现假阴性，测定结果的稳定性较好，简便迅速而易于操作。缺点是接触铅后并不迅速升高，临床治愈后并不迅速恢复，测定结果与病情不平行，特异性也不够，评价时应注意这些不足之处。     

Diagnostic specificity of the insular cortex abnormalities in first-episode psychotic disorders

Volume reductions of the insular cortex have been described in schizophrenia, but it remains unclear whether other psychotic disorders such as affective psychosis also exhibit insular cortex abnormalities. In this study, we used magnetic resonance imaging to investigate the gray matter volume of the anterior (short) and posterior (long) insular cortices in 162 first-episode patients with various psychotic disorders (46 schizophrenia, 57 schizophreniform disorder, 34 affective psychosis, and 25 other psychoses) and 62 age- and gender-matched healthy comparison subjects. Patients with schizophrenia showed bilateral volume reduction of the anterior and posterior insular cortices compared with controls, but the remaining first-episode psychosis subgroups had normal insular volumes. The volumes of these insular subregions were significantly smaller in schizophrenia patients than in patients with schizophreniform disorder or affective psychoses. There was no association between the insular cortex volume and daily dosage or type of antipsychotic medication in any patient group. These findings suggest that the widespread volume reduction of the insular cortex is specific to established schizophrenia, implicating its role in the neurobiology of clinical characteristics associated with schizophrenia.     

Alterations in flash evoked potentials (FEPs) in rats produced by 3,3′-iminodipropionitrile (IDPN)

3,3′-Iminodipropionitrile (IDPN) is a neurotoxicant that produces changes in flash evoked potentials (FEPs) 18 weeks after treatment. We examined dose- and time-related effects of IDPN on FEPs at earlier time points than previously studied (52). Adult male Long-Evans rats were given IDPN (0, 100, 200, or 400 mg/kg/day × 3 days, IP) and FEPs were recorded 14 days later. IDPN (400 mg/kg/day) decreased the amplitudes of some of the “early” and “middle” FEP peaks (N₃₀ and N₅₆), and increased the latencies of some early peaks (P₂₁ and P₄₆). A separate group of rats was treated with IDPN (0 or 400 mg/kg/day × 3 days, IP) and FEPs were recorded 1, 3, 7, 14, and 35 days later. The latencies of all portions of FEPs were increased by IDPN, with maximal changes occurring at 7 and/or 14 days. The amplitude of the middle portions of FEPs (peaks N₅₆, P₆₃, N₇₀, P₉₀) were altered as early as day 3, and some changes were observed up to day 14. In contrast, the “late” portion of FEPs (peak N₁₆₀) was affected at later times (days 14 and 35). Corneal opacities were noted on days 3 and 7, but were largely reversible by day 14. In the time-course study, IDPN decreased colonic temperature on days 1, 3, 7, and 14. The present results suggest that IDPN alters both the early FEP peaks related to the initial afferent sensory volley, and cortical processing associated with the middle and later portions of FEPs.     

The influence of dietary fat on the toxicity of orally ingested lead in rats

The influence of dietary fat on the toxicity of orally ingested lead was investigated. Groups of ten male weanling Wistar rats were maintained on diets providing 11.5, 20, 40 or 60% of energy from fat for 8 wk. All diets were supplemented with a low level of lead--1.25 mg Pb (as lead acetate) per 1000 kJ energy in the diet. Groups receiving 11.5 and 20% of energy as fat had similar lead levels for each tissue studied. Raising the fat level to 40 or 60% of energy resulted in significant increases in tissue-lead concentrations with each increment in dietary fat. The groups receiving 60% of energy as fat had more than twice the level of lead in the femur, kidney, liver and brain than the control rats maintained on the diet containing 11.5% energy as fat, even though the amount of lead ingested was the same for all groups. δ-Aminolaevulinic acid dehydratase activity was not affected when dietary fat was increased from 11.5 to 20%. There was a significant reduction in activity when fat was increased to 40 or 60% of energy. Free erythrocyte protoporphyrin was not affected by the level of dietary fat. This work demonstrates that increasing the level of dietary fat significantly increases lead toxicity and indicates the need for further research on the interaction between dietary factors and lead toxicity.     

Chlordimeform produces profound, selective, and transient changes in visual evoked potentials of hooded rats

Rat visual function was tested after acute exposure to chlordimeform (CDM), a formamidine insecticide/acaricide. Adult male Long-Evans rats were surgically implanted with epidural recording electrodes overlying visual cortex and tested 1 week later. Pattern reversal-evoked potentials (PREPs), flash-evoked potentials (FEPs), and FEP recovery ratios were measured after acute CDM administration. Averaged recordings obtained during 200 reversals of a black-and-white square wave grating comprised the PREPs, and those obtained during 128 paired strobe lamp flashes comprised the FEPs. In the first study, which examined dose-response relationships, i.p. injections of 0 (saline), 5, 15, or 40 mg/kg CDM-HCl were administered 30 min prior to testing. The PREP amplitudes showed large dose-related changes in the CDM-treated rats. PREP N1P1 and P1N3 peak-to-peak amplitudes increased more than 200% in the 40 mg/kg group. In contrast, FEP amplitudes and FEP recovery ratios were unchanged by CDM. Both PREP and FEP peak latencies were increased by CDM in dose-related fashions. In the second study, which examined the time course of CDM action, PREPs and paired-pulse FEPs were recorded 3, 6, and 24 h after dosage with either 0 or 40 mg/kg CDM. All evoked potential changes were large at 3 and 6 h, but had returned to control values by 24 h. In summary, acute exposure to CDM temporarily increased both the amplitude and latency of PREPs, but only the latency of FEPs.     

Neurological soft signs in obsessive-compulsive disorder: The effect of co-morbid psychosis and evidence for familiality

Patients with obsessive-compulsive disorder (OCD) have increased rates of neurological soft signs (NSS) when compared to healthy controls. However, previous findings have been confounded by the presence of co-morbidity with disorders themselves associated with increased NSS, such as schizophrenia. Moreover, it remains unclear whether NSS in OCD reflect a vulnerability to this disorder. This study aimed to examine: 1) the severity of NSS in patients with OCD alone, in patients with OCD and co-morbid psychosis (schizophrenia or bipolar disorders), and in healthy controls; and b) whether unaffected first-degree relatives of patients with OCD also demonstrate a higher prevalence rate of NSS than healthy controls. NSS were assessed with the Cambridge Neurological Inventory (CNI) in 100 patients with OCD, 38 patients with OCD and psychosis (22 with bipolar disorders and 16 with schizophrenia), and 101 healthy controls. Forty-seven unaffected first-degree relatives of patients with OCD only were also administered the CNI. Patients with OCD showed significantly higher scores in motor coordination and total NSS than controls, and patients with OCD co-morbid with psychosis also showed significantly higher scores in motor coordination and total NSS than controls. Although there were no differences in NSS between patients with OCD only and OCD and psychosis as a whole, patients with OCD co-morbid with schizophrenia showed significantly higher scores in motor coordination than patients with OCD, patients with OCD and bipolar disorder, and healthy controls. Unaffected first-degree relatives only showed a higher prevalence rate than healthy controls in specific motor coordination signs, such as Opposition and Extinction. These findings suggest that patients with OCD exhibit more NSS than healthy controls, and that motor coordination signs may be even more extensive when OCD is co-morbid with psychosis. Some of these abnormalities may be indicative of a vulnerability to these disorders, as indicated by their presence in un-affected first-degree relatives.