Contribution of different somatosensory afferent input to subcortical somatosensory evoked potentials in humans

ObjectivesTo investigate the subcortical somatosensory evoked potentials (SEPs) to electrical stimulation of either muscle or cutaneous afferents.MethodsSEPs were recorded in 6 patients suffering from Parkinson’s disease (PD) who underwent electrode implantation in the pedunculopontine (PPTg) nucleus area. We compared SEPs recorded from the scalp and from the intracranial electrode contacts to electrical stimuli applied to: 1) median nerve at the wrist, 2) abductor pollicis brevis motor point, and 3) distal phalanx of the thumb. Also the high-frequency oscillations (HFOs) were analysed.ResultsAfter median nerve and pure cutaneous (distant phalanx of the thumb) stimulation, a P1-N1 complex was recorded by the intracranial lead, while the scalp electrodes recorded the short-latency far-field responses (P14 and N18). On the contrary, motor point stimulation did not evoke any low-frequency component in the PPTg traces, nor the N18 potential on the scalp. HFOs were recorded to stimulation of all modalities by the PPTg electrode contacts.ConclusionsStimulus processing within the cuneate nucleus depends on modality, since only the cutaneous input activates the complex intranuclear network possibly generating the scalp N18 potential.SignificanceOur results shed light on the subcortical processing of the somatosensory input of different modalities.     

Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver.The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world.We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV.The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1.     

Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

老年高血压患者脉压与急性心肌梗塞的关系

目的探讨老年原发性高血压（ET）患者脉压与急性心肌梗塞（AMI）的关系。方法观测45例老年高血压病合并急性心肌梗塞患者的收缩压（SBP）、舒张压（DBP）及脉压（PP），以31例老年单纯高血压患者（冠脉造影排除冠心病）作对照组，进行比较。结果并发急性心肌梗塞组，其脉压较单纯高血压组明显增高。结论脉压与老年人急性心肌梗塞密切相关，对老年人高血压的治疗更要注重控制脉压。     

人血清胰岛素抗体、猪胰岛素原抗体和胰多肽抗体的放射免疫检测法

作者用自制的[~(125)I]标记激素,参考国外经验,建立了人血清胰岛素抗体、猪胰岛素原抗体和胰多肽抗体等三种放射免疫检测法,并对方法的主要实验条件进行了优选,对方法的质量控制参数作了验证。结果发现:在使用国产胰岛素的糖尿病人血清中,三种抗体的检出率分别为90.8％、48.3％和36.5％;抗体特异性结合值分别为21.2±17.4％、41.8±27.4％和25.6±28.4;而正常人和糖尿病人未用胰岛素者全部为阴性,显示国产胰岛素具有明显的免疫原性。     

白细胞介素-18基因修饰的胎肝细胞经脾移植对小鼠免疫功能的影响

目的：观察表达mIL-18的重组腺病毒基因修饰的胎肝细胞（AdmIL-18/BNL.CL2)经脾移植对正常小鼠免疫功能的影响。方法：实验组小鼠经脾移植AdmIL-18/BNL.CL2，同时设LacZ病毒对照组（Ad-LacZ/BNL.CL2),BNL.CL2细胞对照组及空白对照组。2周后处死，留取血清，制备腹腔巨噬细胞、脾淋巴细胞、肝组织匀浆液，提取肝组织总RNA。采用ELISA法检测各组小鼠血清、腹腔Mφ和脾细胞培养上清、肝匀浆中细胞因子的含量；采用半定量RT－PCR法，检测肝组织细胞因子mRNA相对表达量；以LDH释放法测定腹腔Mφ杀伤活性和脾NK细胞活性，用MTT还原比色法测定脾淋巴细胞的增殖活性。结果：实验组小鼠血清、细胞培养上清及肝匀浆中，IL－18、IL－2、IFN－γ、TNF-α稔均高于其它对照组，而IL－4、IL－10水平则低于对照组；半定量RT－PCR结果与ELISA检测结果一致；同时，实验组腹腔Mφ的杀伤活性和脾NK细胞活性，及脾淋巴细胞增殖活性也明显高于对照组。结论：AdmIL-18能有效转染至胎肝细胞并稳定表达mIL-18;AdmIL-18基因修饰的胎肝细胞经脾移植后，可显著提高肝脏、脾脏免疫细胞活性，活化腹腔Mφ，促进Th1类细胞因子表达，抑制Th2类细胞因子的分泌。     

老年冠心病患者实施健康教育的远期效果分析

目的：探讨老年冠心病患者实施健康教育的远期效果。方法：110例老年冠心病患者被随机分为健康教育组（教育组）及对照组，每组各55例。在常规治疗的基础上教育组在住院期间及出院后4年内给予健康教育处方结合口头卫生宣教及科普板报知识等经常性的健康教育活动，而对照组不予健康教育。结果：教育组患者对冠心病知识的了解情况、饮食控制情况、规律服药治疗情况比对照组好（P＜0．01），出院后再次住院次数比对照组少（P＜0．01）。而情绪及吸烟量控制两组无显著性差异（P＞0．05）。结论：对老年冠心病患者实施经常性的健康教育是控制疾病恶化的重要措施。     

18氟-氟化脱氧葡萄糖在下咽部肿瘤诊断中的作用

目的：研究^18氟—氟化脱氧葡萄糖(^18F-FDG)在下咽部肿瘤诊断中的作用。方法：20例下咽部肿瘤患者均接受^18F-FDG检查及CT、全组内镜(食管、咽喉、气管镜)检查。结果：20例下咽部肿瘤患者^18F-FDG检查结果显示：2例阴性；18例肿瘤原发部位有同位素浓集，其中5例伴异位同位素浓集。对此5例患者进一步临床、病理检查证实：1例食管部占位，2例肺部病变，2例为良性改变。^18F-FDG检查结果显示的病变范围与CT、内镜检查相符。结论：^18F-FDG检查可以提高下咽部肿瘤、尤其是隐匿的并发肿瘤诊断的准确性，明确病变范围，为临床治疗提供依据；同时又是一个简单、易行的下咽部肿瘤的随访检查手段。