G试验水平对艾滋病合并肺孢子菌肺炎机械通气患者脱机结局的预测价值

目的 探讨G试验能否预测艾滋病合并肺孢子菌肺炎(PCP)机械通气患者的撤机.方法 回顾性分析北京佑安医院感染科监护病房2010年5月至2017年5月收治的艾滋病合并重症PCP且行机械通气治疗患者的临床资料,根据患者脱机成功与否将患者分为两组,比较两组患者G试验水平.结果 共入选49例患者,脱机成功组9例,失败组40例.两组患者基线资料比较结果显示,白蛋白、CD4计数、G试验水平差异均有统计学意义(P均＜0.05).成功组G试验水平显著低于失败组,分别为331.0 ng/L(299.0～488.7 ng/L)和267.0 ng/L(236.0～294.5 ng/L).多因素分析结果显示,血清G试验水平是影响艾滋病合并重度PCP患者能够脱机与否的独立危险因素(0R=0.978,95％CI:0.959～0.998,P=0.032).结论 G试验可以作为一项脱机结局预测指标,用来预测艾滋病合并PCP患者撤机预后.     

The use of intravenous pentamidine for the prophylaxis of Pneumocystis pneumonia in pediatric patients

Pneumocystis jiroveci pneumonia was common in the immunocompromised host before the widespread use of prophylaxis. When trimethoprim–sulfamethoxazole is not tolerated, prophylaxis with intravenous pentamidine (IVP) may be initiated. We performed a retrospective analysis of all pediatric patients who received IVP regarding efficacy, safety, and reason for initiation. Of 106 patients included in our analysis, one patient tested positive for Pneumocystis DNA. Adverse events were reported in 18% of IVP courses, and main reason for initiation was cytopenia (59%). We found IVP to be effective and safe, and recommend the use of IVP in pediatric patients in whom first‐line prophylaxis is contraindicated.     

The mGlu2 but not the mGlu3 receptor mediates the actions of the mGluR2/3 agonist, LY379268, in mouse models predictive of antipsychotic activity

Rationale Group II metabotropic glutamate receptors (mGluRs) comprise the mGluR2 and mGluR3 subtypes, the activation and modulation of which has been suggested to be beneficial for treating schizophrenia. Genetic association studies suggest limited association between mGluR2 and schizophrenia but some association between mGluR3 and schizophrenia. Conversely, pre-clinical studies suggest that mGluR2 may be responsible for mediating the antipsychotic activity of mGluR2/3 agonists, although to date, the role of mGluR3 has not been specifically assessed. Objectives The aim of this study is to use recently generated mGluR3 and mGluR2 knockout mice to investigate which of the group II mGluRs mediates the actions of the mGluR2/3 agonist, LY379268, in two mouse models predictive of antipsychotic activity. Materials and methods LY379268 (0.3–10 mg/kg SC), phencyclidine (PCP; 1–5 mg/kg IP), and amphetamine 1–10 mg/kg IP) were assessed on locomotor activity and behaviour in C57Bl/6J and transgenic mice. LY379268 was then assessed on PCP (5 mg/kg IP)- and amphetamine (2.5 mg/kg IP)-induced hyperactivity and behaviour in C57Bl/6J and transgenic mice. Results PCP (5 mg/kg)-evoked hyperactivity and behavioural alterations, i.e. circling, falling, stereotypy and ataxia, as well as amphetamine (2.5 mg/kg)-evoked hyperactivity, were dose-dependently attenuated by LY379268 (0.3–3 mg/kg) in C57Bl/6J mice. One milligram per kilogram of LY379268 reversed PCP-evoked hyperactivity and behavioural alterations in wild-type (WT) and mGluR3 knockout mice but not in mice lacking mGluR2. Similarly, 3 mg/kg LY379268 reversed amphetamine-evoked hyperactivity in WT and mGluR3 knockout mice but not in mice lacking mGluR2. Conclusion The mGlu2 but not the mGlu3 receptor subtype mediates the actions of the mGluR2/3 agonist, LY379268, in mouse models predictive of antipsychotic activity.     

Effect of chronic administration of NMDA antagonists on synaptic development

The current research assessed the role of the N-methyl-D-aspartate (NMDA) receptor in developmental synaptic plasticity. This was accomplished by quantitative analysis of synaptic number and morphology following pharmacological manipulation of NMDA receptor activity using either the competitive antagonist 2-amino-5-phosphonovaleric acid (APV) or the noncompetitive antagonist phencyclidine (PCP). In the first group, 15-day-old male Long-Evans rats were implanted with osmotic minipumps, which administered 50 mM APV or vehicle at a rate of 0.5 μl per h into the subjects' occipital cortex for 14 days. At age 30 days (P30), the rats were sacrificed and their occipital neocortices were examined. A second group of rats was given subcutaneous injections of 10 mg/kg PCP or vehicle once daily beginning on P5 for a period of 15 days, and was sacrificed on P20. To determine the effects following withdrawal from long-term NMDA antagonism, a third group of animals was given the same PCP injection routine until P20, but was sacrificed on P21, P26, P36, and P56. Developmental administration of APV was associated with a decreased molecular layer depth and estimated total number of synapses. Similarly, PCP induced a reduction in brain weight, molecular layer depth, and estimated total number of synapses. Withdrawal from NMDA antagonism was initially associated with similar results, i.e., reduced brain weight, cortex depth, synaptic density, and estimated total number of synapses, along with an increase in synaptic length. By P36, however, there was a transitory rebound associated with increased molecular layer depth and estimated total number of synapses. These results support the suggestion that NMDA receptor activation is integral to naturally occurring developmental synaptogenesis, and underscore the importance of NMDA receptor involvement in the process of synaptic plasticity. Synapse 26:104–113, 1997. © 1997 Wiley-Liss, Inc.     

中西医结合治疗艾滋病卡氏肺孢子虫肺炎38例

目的：观察中西医结合治疗艾滋病卡氏肺孢子虫肺炎的疗效。方法：采用西药配合真武汤合葶苈大枣泻肺汤每日1剂,21d为1疗程,治疗38例。结果：38例中,显效28例,有效7例,无效3例,有效率92.20%。结论：该治疗方案可明显减轻和改善患者的症状与体征。     

Inhibition of soluble epoxide hydrolase contributes to the anti-inflammatory effect of antimicrobial triclocarban in a murine model

The increasing use of the antimicrobial triclocarban (TCC) in personal care products (PCPs) has resulted in concern regarding environmental pollution. TCC is a potent inhibitor of soluble epoxide hydrolase (sEH). Inhibitors of sEH (sEHIs) are anti-inflammatory, anti-hypertensive and cardio-protective in multiple animal models. However, the in vivo effects anticipated from a sEHI have not been reported for TCC. Here we demonstrated the anti-inflammatory effects in vivo of TCC in a murine model. TCC was employed in a lipopolysaccharide (LPS)-challenged murine model. Systolic blood pressure, plasma levels of several inflammatory cytokines and chemokine, and metabolomic profile of plasma oxylipins were determined. TCC significantly reversed LPS-induced morbid hypotension in a time-dependent manner. TCC significantly repressed the increased release of inflammatory cytokines and chemokine caused by LPS. Furthermore, TCC significantly shifted the oxylipin profile in vivo in a time-dependent manner towards resolution of inflammation as expected from a sEHI. These results demonstrated that at the doses used TCC is anti-inflammatory in the murine model. This study suggests that TCC may provide some benefits in humans in addition to its antimicrobial activities due to its potent inhibition of sEH. It may be a promising starting point for developing new low volume high value applications of TCC. However these biological effects also caution against the general over use of TCC in PCPs.     

艾滋病合并卡氏肺孢子菌肺炎20例疗效观察

目的：探讨艾滋病合并卡氏肺孢子菌肺炎（PCP）的临床特征和治疗方法。方法：回顾性分析20例艾滋病合并PCP患者的临床表现、影像特征及治疗效果等临床资料。结果：该病以发热伴进行性呼吸困难、紫绀等为临床表现,缺乏特异性症状和特征,而影像学改变呈双肺弥漫渗出性病变、肺门、纵隔淋巴结肿大为主还可见局限性渗出性病变、胸腔积液等。结论：结合HIV感染病史,加强对本病的临床表现和影像学知识的认识、及时的诊断性治疗是正确诊断的主要措施。复方新诺明是治疗艾滋病合并卡氏肺孢子菌肺炎安全有效的药物。     

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.     

Pneumocystis jirovecii pneumonia is rare in renal transplant recipients receiving only one month of prophylaxis

Prophylaxis against Pneumocystis jirovecii pneumonia (PCP) is recommended for at least 4–12 months after solid organ transplant. In our center, renal transplant recipients receive only 1 month of post‐transplant trimethoprim–sulfamethoxazole, which also may provide limited protection against Nocardia. We identified only 4 PCP cases and 4 Nocardia cases in 1352 patients receiving renal and renal‐pancreas transplant from 2003 to 2009 at the University of Michigan Health System. Two PCP cases were identified <1 year after transplant, and 2 PCP cases were identified >1 year after transplant (gross attack rate 4/1352, 0.3%). Two Nocardia cases were identified <1 year after transplant, and 2 cases were identified >1 year after transplant. All identified cases received induction therapy (7 of 8 with anti‐thymocyte globulin), whereas about one‐half of all renal transplant patients received induction therapy at our institution. No patient was treated for rejection within 6 months of PCP; 2 of 4 patients with PCP had recent cytomegalovirus infection. All patients with PCP and 3 of 4 patients with Nocardia survived. The benefits of prolonged PCP prophylaxis should be weighed against the adverse events associated with prolonged use of antimicrobials.