A steroid recognition site is functionally coupled to an expressed GABAA-benzodiazepine receptor

Pregnane steroids, particularly 3α-hydroxylated metabolites of progesterone, are known to have rapid and profound effects on brain excitability. Recent evidence suggests that the γ-aminobutyric acid (GABA_A)-benzodiazepine receptor-Cl⁻ ionophore complex may mediate these actions. The data further suggest that these steroids modulate the complex through a novel site independent of other known sites on the complex. The hypothesis that this site is on the GABA_A-benzodiazepine receptor-Cl⁻ ionophore complex is tested in the present study by determining its presence on transiently expressed GABA_A-benzodiazepine receptors.     

The influence of age on the inducibility of rat liver cytochrome P450IA1 (CYPIA10 and P450IA2 (CYPIA2) mRNAs

The levels of the messenger RNAs for the cytochromes P450IA1 (CYPIA1) and P450IA2 (CYPIA2) were determined in liver cytoplasmic RNA of rats of various ages after maximal induction with either 3-methylcholanthrene or isosafrole and in untreated rats. An increase in the CYPIA1 mRNA levels was observed only after treatment with 3-methylcholanthrene, whereas both 3-methylcholanthrene and isosafrole were able to induce the levels of CYPIA2 mRNA. The study presented here shows that the maximal induction of these 2 mRNAs did not change with age when 3-methylcholanthrene was used as the inducing agent. Isosafrole induction did not yield higher CYPIA1 mRNA levels in young rats but reduced the amount of this mRNA in old animals to levels below the detection limit of our assay. After induction with isosafrole the levels of the CYPIA2 mRNAs in the older age groups were lower than those observed in young rats. It is concluded that with age the responsiveness to cytochrome P450 inducers may change. This change is different for the various cytochrome P450 enzymes and depends on which inducer is used.     

Lens hygiene and care system contamination of asymptomatic rigid gas permeable lens wearers

Rigid gas permeable contact lenses are associated with fewer serious adverse reactions and thereby offer an increased margin of safety despite a perceived less strict adherence to sterile care system components. This article presents the lens care habits and frequency of care system contamination found in asymptomatic rigid gas permeable lens wearers. Forty-one asymptomatic rigid lens wearers presented for study. After in-office lens insertion, the lens case and solutions were sent for bacterial, fungal, and acanthamoeba cultures. The lens care habits of the subjects were determined via questionnaire. At least 1 + bacterial growth was found in 34% of cases and 25% of solutions. No fungal or acanthamoeba contamination was found. The date of expiration is a poor predictor of solution sterility. Although most subjects reported washing their hands before handling lenses, 56% used tap water to rinse their lenses immediately before insertion. All stored their lenses wet, with 90% using an appropriate rigid gas permeable soaking solution. The increased margin of safety offered by rigid lenses is not the result of better efficacy of care systems. Rigid lens wearers should be reminded that the use of tap water to rinse lenses after disinfection and before insertion is inappropriate. Furthermore, it should be emphasized that the dates of expiration on solutions should not be used as the time to discard solutions. Data to demonstrate a reduction of care system contamination when tap water is eliminated would provide further evidence that the use of tap water including before disinfection should be discouraged.     

T-cell receptor sequencing reveals hepatocellular carcinoma immune characteristics according to Barcelona Clinic liver cancer stages within liver tissue and peripheral blood

Analysis of T-cell receptor (TCR) repertoires in different stages of hepatocellular carcinoma (HCC) might help to elucidate its pathogenesis and progression. This study aimed to investigate TCR profiles in liver biopsies and peripheral blood mononuclear cells (PBMCs) in different Barcelona Clinic liver cancer (BCLC) stages of HCC. Ten patients in early stage (BCLC_A), 10 patients in middle stage (BCLC_B), and 10 patients in late stage (BCLC_C) cancer were prospectively enrolled. The liver tumor tissues, adjacent tissues, and PBMCs of each patient were collected and examined by TCR β sequencing. Based on the ImMunoGeneTics (IMGT) database, we aligned the V, D, J, and C gene segments and identified the frequency of CDR3 sequences and amino acids sequence. Diversity of TCR in PBMCs was higher than in both tumor tissues and adjacent tissues, regardless of BCLC stage and postoperative recurrence. TCR clonality was increased in T cells from peripheral blood in advanced HCC, compared with the early and middle stages. No statistical differences were observed between different BCLC stages, either in tumors or adjacent tissues. TCR clonality revealed no significant difference between recurrent tumor and non-recurrent tumor, therefore PBMCs was better to be representative of TCR characteristics in different stages of HCC compared to tumor tissues. Clonal expansion of T cells was associated with low risk of recurrence in HCC patients.     

替尼泊苷与尼莫司汀联合方案治疗肺癌脑转移瘤近期疗效分析

背景与目的：脑转移瘤的原发肿瘤以肺癌最为常见，肺癌脑转移瘤患者治疗效果并不理想。本研究应用替尼泊苷（VM-26）和尼莫司汀（ACNU）联合方案治疗肺癌脑转移瘤患者，观察其对肺癌脑转移瘤的临床治疗效果，评价其不良反应。方法：2006年12月至2008年5月，中国抗痛协会神经肿瘤专业委员会组织全国15家单位对经手术或病理活检确诊的肺癌脑转移瘤患者，应用VM-26与ACNU联合方案化疗，观察近期疗效。化疗方案为VM-26，每天80～100mg／m^2，d1-3；6-8周重复一次；ACNU，2-3mg／kg，d1，6-8周重复一次。结果：278例患者资料完整、可行近期疗效评价，上述病例共行897周期化疗，平均3．2个周期。全组无完全缓解（complete response，CR）病例，77例（27．7％）部分缓解（partial response，PR），139例（50％）稳定（stable disease，SD），62例（22.3％）进展（progressive disease，PD）。客观有效率（CR＋PR）为27．7％，疾病控制率（CR＋PR＋SD）为77．7％。化疗的主要剂量限制性毒性为骨髓抑制，Ⅲ、Ⅳ度中性粒细胞减少症发生率分别为23．1％（207／897）；20.1％（180／897），Ⅲ、Ⅳ级血小板减少症发生率分别为19．6％（176／897）、14．5％（130／897）。按既往是否接受化疗，患者可分为既往接受化疗组、未接受化疗组，前者较之后者，Ⅳ度中性粒细胞减少症、Ⅳ度血小板减少症、Ⅲ及Ⅳ度中性粒细胞减少症、Ⅲ度及Ⅳ度血小板减少症发生率均明显升高（P均〈0．05）。结论：VM-26与ACNU联合方案主要毒性为Ⅲ、Ⅳ度骨髓抑制，在既往行化疗患者发生率较高，但可控制。该方案治疗肺癌脑转移瘤，客观有效率与其它常用方案相似、疾病控制率较高。     

顺铂磁性纳米药物的安全性评价

目的:初步评价顺铂磁性纳米药物的安全性。方法:以昆明种小鼠和豚鼠为实验动物,经尾静脉注射顺铂磁性纳米药物进行急性毒性实验和全身过敏性实验,并以顺铂注射液为对照,比较2种制剂的半数致死量(LD50)和过敏反应强度。结果:小鼠顺铂磁性纳米药物及顺铂注射液的LD50分别为15.618、18.087mg·kg-1,但未见前者对豚鼠有致敏作用,后者过敏反应为阳性。结论:顺铂经改性为磁性纳米药物后在一定剂量范围内毒性并没有明显增加,没有致敏作用。