Phencyclidine (PCP): Some human studies

Studies on the effects of PCP have been conducted in volunteers in the Army Laboratories and elsewhere and in illicit users. The present review has summarized the observations of many investigators which showed that the acute effects of PCP following several routes of administration were shown to be dose-related. High doses of PCP produce disturbing manifestations including psychosis, numbness, light-headedness, vertigo, ataxia, and nystagmus due to acute intoxication. Furthermore, some subjects became irritable, argumentative or negative under the conditions of social stress and demanding tasks. In addition to a variety of central action, PCP has also been shown to affect cardiovascular function, heat storage, and exercise performance. PCP can also induce, although rarely, prolonged toxic psychosis in chronic abusers and precipitate psychotic episodes in psychotic and prepsychotic personalities. Tolerance, but not physical dependence, develops to the effects of PCP. Psychologic dependence as indicated by craving for the drug has however been reported.     

Properties of the phencyclidine (PCP) receptors

1. 1. [³H]Phencyclidine (PCP, Angel Dust) receptors have been characterized using a rat brain binding section technique.

2. 2. [³H]PCP labels a single class of site in rat brain (k_d = 46 nM; B_max = 10.5 fold/slice). Ligand selectivity pattern strongly suggests that [³h]pcp binds to sites relevant for its pharmacological actions.

3. 3. Chronic PCP treatment (10 mg/kg/day for 14 days) decreases the number of sites (B_max) for [³H]PCP and [³H]spiperone binding but not for [³H]dihydromorphine. These modifications could be related to the development of tolerance and dependence to PCP.

4. 4. Visualization of [³H]PCP binding sites shows high densities of receptors in cortical areas and hyppocampus. Lower densities are observed in caudate-putamen, nucleus accumbens, and amygdala. Negligible quantities of receptors are seen in brain stem and over white matter.

5. 5. The presence of specific [³h]pcp binding sites in rat brain suggests the possible existence of an endogenous ligand for this unique receptor.

Gestational exposure to phencyclidine (PCP) in rats decreases PCP binding sites in term fetal brain

Pregnant Sprague-Dawley rats were treated with 5 mg/kg body weight of phencyclidine (PCP) injected at 1 ml/kg subcutaneously on three consecutive days at four different stages of gestation. Within 10–30 min after treatment, dams showed some lack of motor coordination and became lethargic. On gestational day 21, all rats were killed by decapitation and brains were dissected and stored from mother and fetus for neurochemical analysis. PCP, dopamine and muscarinic cholinergic receptor binding was measured in membranes prepared from maternal and fetal whole brain. Neurotransmitter concentrations were also measured in the fetal brain homogenates. There was a significant decrease in PCP binding sites in fetal but not maternal brains after maternal PCP injection at gestational days 12–14, 15–17 and 18–20, but not at 9–11 days. Dopamine and muscarinic cholinergic receptor binding was not significantly altered in fetal or maternal brain when compared with vehicle control animals. The whole brain dopamine, 3,4-dihydroxyphenylacetic acid, serotonin, and 5-hydroxyindoleacetic acid concentrations did not show significant change in any group studied. These data indicate that gestational exposure to PCP decreases high affinity binding of PCP in term fetal brain at doses which do not alter maternal PCP receptor binding.     

Effect of psychotomimetics and some putative anxiolytics on stress-induced hyperthermia

Summary Stress-induced hyperthermia (SIH), which is seen in the last mice removed from the cage, is a novel animal model sensitive to anxiolytic drugs. SIH is antagonized by CL 218872 (25 and 50 mg/kg, os), by tracazolate (5 and 7.5 mg/kg, ip) and by 2-AP-5 (50 and 100 mg/kg, ip). At higher dose, CL 218872 (100 mg/kg, os) and tracazolate (12.5 mg/kg, ip) lose their activity.PK 9084 (5–40 mg/kg, ip) and CGS 9896 (2–20 mg/kg, both ip and os) were also ineffective in preventing SIH. The anti-hyperthermic effect of CL 218872 (25 mg/kg) and tracazolate (7.5 mg/kg) was blocked by the benzodiazepine antagonist Ro 15–1788 (15 mg/kg). CGS 9896 (10 mg/kg, os) also reversed the effect of CL 218872 (25 mg/kg) on SIH.Differently from anxiolytics, MK-801 (0.5–1 mg/kg, os), PCP (2.5 mg/kg, ip) and d-amphetamine (10 mg/kg, ip) evoked hyperthermia in the first set of mice and prevented a further stress-induced rise of body temperature in the last set of mice.     

Diagnosis of pneumocystis pneumonia using serum (1-3)-β-D-Glucan: a bivariate meta-analysis and systematic review

Background

The (1-3)-β-D-Glucan (BG) assay has been approved for making a diagnosis of invasive fungal disease. However, the role of serum-BG assay for the diagnosis of pneumocystis pneumonia (PCP) is controversial, especially between patients with human immunodeficiency virus (HIV) and non-HIV. We conducted a meta-analysis to determine the difference of the overall accuracy of serum-BG assay for the diagnosis of PCP in immunocompromised patients with and without HIV.

Methods

After a systematic review of English-language studies and manual researching, sensitivity (Se), specificity (Sp), and other measures of accuracy of serum-BG for the diagnosis of PCP were pooled using random-effects models for bivariate meta-analysis. Summary receiver operating characteristic (SROC) curve was used to summarize overall test performance. Subgroup analyses were performed to explore the heterogeneity in Se and Sp.

Results

Thirteen studies met our inclusion criteria. The summary estimates for serum-BG assay for definite PCP were as follows: Se, 0.91 [95% confidence interval (CI), 0.88–0.93]; Sp, 0.75 (95% CI, 0.68–0.81). As for the patients with and without HIV, the Se and Sp were 0.92 and 0.78, 0.85 and 0.73, respectively. Significant heterogeneity between Se was presented (P=0.04).

Conclusions

Contrary to the results of the previous meta-analysis, a negative result of serum-BG determination is sufficient for ruling out PCP only in HIV cases. For non-HIV patients, the results should be interpreted in parallel with clinical and radiological findings. Besides, further prospective studies with larger sample size are needed to confirm the diagnosis strategy of BG detection.     

A Nationwide Survey of the Management of Unintentional—Low Dose Tricyclic Antidepressant Ingestions Involving Asymptomatic Children: Implications for the Development Of an Evidence-Based Clinical Guideline

Background: The triage of unintentional tricyclic and cyclic antidepressant ingestions involving children <6 years seems based on single cases or small studies. Walsh, in describing 2 cases involving 15–20 mg/kg ingestions, recommended hospitalizing all children ingesting tricyclic and cyclic antidepressants. Objective: To evaluate the patterns of triage for pediatric tricyclic and cyclic antidepressants practiced by regional poison control centers nationwide, and to determine the amount ingested (mg/kg) that resulted in referral to the emergency department, including the recommended duration of observation time for asymptomatic children. Second, to analyze the cost implications, as well as the need for a practice guideline based on severity stratification. Methods: We sent a survey to 44 major regional poison control centers. We reviewed Health Care Financing Administration's tricyclic and cyclic antidepressants management related costs. Results: Thirty centers responded (68%). Eighty-seven percent of all centers send children, regardless of dose ingested, to the emergency department. Four out of the 30 recommended observation based on dose in mg/kg ingested (range >1.5–5). Recommended observation times in the emergency department varied between 6–24 hours. Twenty-seven (90%) Poison Control Centers recommended 6 hours (although one recommended doing so only after administering activated charcoal). One recommended 6–12 hours of observation and 2 Poison Control Centers recommended 24-hour observation. Only 1 center recommended obtaining tricyclic and cyclic antidepressant plasma levels. Discussion: In our review of the literature, the lowest toxic dose reported was 6.7 mg/kg. This is consistent with our Poison Control Center data over the past 5 years where no child was toxic at doses <5 mg/kg. While only 13% of the centers surveyed utilize a stratification strategy to triage pediatric tricyclic and cyclic antidepressant ingestions, the current referral patterns support evaluation based on pharmacokinetics, not worst case incidents. Conclusion: This survey demonstrates that most children with tricyclic and cyclic antidepressant ingestions will be sent to the emergency department, regardless of the amount ingested. A prospective study is needed to determine the probable dose of tricyclic and cyclic antidepressant ingestions that requires observation at a health care facility.     

肺孢子菌肺炎大鼠肺泡巨噬细胞吞噬功能及TNF-αIL-6的变化

目的观察肺孢子菌肺炎（PCP）大鼠肺泡巨噬细胞（AM）吞噬功能及支气管肺泡灌洗液（BALF）、AM培养上清TNF-α、IL-6的变化。方法 Wistar大鼠连续肌肉注射地塞米松建立免疫抑制PCP模型,检测大鼠AM吞噬功能及BALF、AM培养上清TNF-α、IL？6水平,同时设正常对照组。结果 PCP模型组大鼠AM吞噬鸡红细胞百分率为（20.61±2.04）%,吞噬指数为0.25±0.21,均明显低于对照组的（25.45±3.1）%和0.31±0.16（P均〈0.05）。BALF中TNF？α为（16.84±0.86）pg/ml,IL？6为（1.05±0.19）pg/ml,均明显高于对照组的（12.48±0.84）pg/ml和（0.86±0.11）pg/ml（P均〈0.05）;AM培养上清中TNF？α、IL？6差异均无统计学意义（P均〉0.05）。结论使用糖皮质激素造成大鼠免疫抑制诱发PCP后,大鼠AM吞噬功能降低,BALF中TNF-α、IL-6水平升高。     

Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects

The planar cell polarity (PCP) pathway controls the process of convergent extension (CE) during gastrulation and neural tube closure, and has been implicated in the pathogenesis of neural tube defects (NTDs) in animal models and human cohorts. In this study, we analyzed the role of one core PCP gene PRICKLE1 in these malformations. We screened this gene in 810 unrelated NTD patients and identified seven rare missense heterozygous mutations that were absent in all controls analyzed and predicted to be functionally deleterious using bioinformatics. Functional validation of five PRICKLE1 variants in a zebrafish model demonstrated that one variant, p.Arg682Cys, antagonized the CE phenotype induced by the wild-type zebrafish prickle1a (zpk1a) in a dominant fashion. Our study demonstrates that PRICKLE1 could act as a predisposing factor to human NTDs and further expands our knowledge of the role of PCP genes in the pathogenesis of these malformations.     

论BIPAP呼吸机治疗高龄COPD合并PCP患者的护理研究

目的 探讨BIPAP呼吸机治疗高龄慢性阻塞性肺炎(COPD)合并卡氏肺囊虫肺炎PCP患者的护理方法及其效果.方法 回顾性分析了2007年01月至2011年01月入住我院的4例高龄COPD合并PCP患者的临床资料,对其实施常规吸氧、解痉平喘等处理,应用激素与抗感染等治疗手段,同时给予其鼻(面)罩BIPAP机械通气治疗.主要对治疗前后患者尿液中的IgA、IgG、IgM、动脉血气变化、心率、呼吸频率及血压等进行比较分析,数据用卡方检验(检验)的方法进行检验,组间差异以P＜0.05表示具有统计学意义.结果 (1)本组患者在治疗前尿液中的IgA、IgG、IgM含量分别为(1.4±0.5)mg/L、(0.8 ±0.3)mg/L、(0.1±0.02)mg/L,治疗后上述三个指标值分别为(0.7±0.3)mg/L、(0.3±0.2) mg/L、(0.02±0.01) mg/L,前后存在显著的统计学差异(P＜0.01);(2)治疗前患者PO2、PCO2及SO2(％)分别为(7.56±1.62) kPa、(9.69±1.52) kPa、(83.2±5.2),治疗后上述各值分别为(9.38±1.57) kPa、(8.13±1.29) kPa、(95.7±3.28),上述各个指标在治疗前后存在统计学差异(P＜0.05);(3)治疗前患者呼吸频率(R,次/分)、心率(次/分)、SBP(次/分)、DBP(次/分)分别为(29.3±5.6)、(119.3±13.2)、(143.9±11.2)、(79.3±7.4),治疗后患者上述指标值分别为(17.1±3.2)、(83.3±8.2)、(139.5±10.8)、(78.9±7.2),上述各指标中,治疗前后存在统计学差异的为呼吸频率、心率(P＜0.05),后两者在治疗前后不存在统计学差异(P＞0.05).结论 运用BIPAP呼吸机治疗及护理观察高龄COPD合并PCP患者,疗效显著且安全,应该在临床上加以推广并应用.