Apolipoprotein B metabolism in normal,type IV,and type V hyperlipoproteinemic subjects

Apolipoprotein B (apoB) metabolism was investigated in four normal, three type IV, and three type V hyperlipoproteinemic subjects. Following injection of autologous radioiodinated very low density lipoprotein (VLDL) the rate of clearance of the apoprotein from this particle and its subsequent appearance in low density lipoprotein (LDL) was measured by frequent apoB specific activity determinations over an 11-day period. The resultant data were analyzed using the SAAM 27 computer program. In the normal subjects, more than 95% of the injected VLDL apoB was rapidly transferred to the LDL density range and accounted for all LDL apoB synthesis in that group. The plasma VLDL apoB concentration in the type IV group was, on average, five times the normal level. This resulted primarily from a doubling of the VLDL apoB synthetic rate associated with a defective or saturated catabolic mechanism. Only 60% of this material subsequently appeared in LDL, while the remainder was catabolized via an LDL-independent pathway. The turnover parameters of LDL apoB were normal in the type IV patients. Type V hyperlipoproteinemic subjects exhibited a 12- to 35-fold increase in plasma VLDL apoB concentration over normal. This again derived from increased VLDL apoB synthesis in the presence of defective removal of the apoprotein; the fractional catabolic rate of VLDL apoB in this group was 14% of the normal value. However, in contrast to the type IV patient data, more than 85% of the apoB in type V VLDL eventually appeared in LDL whose turnover rate was raised as a result of an increase in its catabolism; the fractional catabolic rate of LDL apoB in type V patients was four-fold above normal. The plasma LDL apoB pool size was substantially reduced in these subjects. This study shows that in hyperlipoproteinemic pheno-types IV and V there exist multiple anomalies of apoB metabolism affecting both VLDL and LDL.     

Effects of ossein-hydroxyapatite compound on ewe bone remodeling: Biochemical and histomorphometric study

Summary Ossein-hydroxyapatite compound (OHC) is a protein-mineral complex derived from bovine bone. Its effects on bone remodeling were studied in old ewes which have seasonal variations in bone remodeling. Seven animals received 200 mg OHC/kg b.w./day for 90 days from July to September. The control group consisted of 7 untreated animals followed for the same period of time. OHC was administered through a fistula into the fourth stomach. A significant decrease of bone histomorphometric parameter values was noted in controls at the end of the experiment, due to seasonal variations: the cancellous eroded perimeter decreased by 45%, the osteoblastic perimeter by 60% and the bone formation rate at the cell level by 20%. In contrast, in the treated-group, these parameters tended to increase or did not change. In conclusion, counteracting the significant seasonal reduction of bone remodeling in ewes, OHC seems able to stimulate directly or indirectly bone metabolism, especially when osteoblast activity is reduced and may partly prevent the seasonal reduction of bone turnover.     

The Discovery and Development of Boceprevir: A Novel,First-generation Inhibitor of the Hepatitis C Virus NS3/4A Serine Protease

An estimated 2–3% of the world''s population is infected with hepatitis C virus (HCV), making it a major global health problem. Consequently, over the past 15 years, there has been a concerted effort to understand the pathophysiology of HCV infection and the molecular virology of replication, and to utilize this knowledge for the development of more effective treatments. The virally encoded non-structural serine protease (NS3) is required to process the HCV polyprotein and release the individual proteins that form the viral RNA replication machinery. Given its critical role in the replication of HCV, the NS3 protease has been recognized as a potential drug target for the development of selective HCV therapies. In this review, we describe the key scientific discoveries that led to the approval of boceprevir, a first-generation, selective, small molecule inhibitor of the NS3 protease. We highlight the early studies that reported the crystal structure of the NS3 protease, its role in the processing of the HCV polyprotein, and the structural requirements critical for substrate cleavage. We also consider the novel attributes of the NS3 protease-binding pocket that challenged development of small molecule inhibitors, and the studies that ultimately yielded milligram quantities of this enzyme in a soluble, tractable form suitable for inhibitor screening programs. Finally, we describe the discovery of boceprevir, from the early chemistry studies, through the development of high-throughput assays, to the phase III clinical development program that ultimately provided the basis for approval of this drug. This latest phase in the development of boceprevir represents the culmination of a major global effort to understand the pathophysiology of HCV and develop small molecule inhibitors for the NS3 protease.     

神经性厌食患者血小板 5-羟色胺浓度的对照研究

目的研究5-羟色胺（5-HT）在神经性厌食发病中的作用。方法采用高效液相色谱法,分别测定37例神经性厌食患者和34例正常对照者的血小板5-HT含量。结果神经性厌食患者血小板5-HT水平[（2.2±1.4）nmol/109个血小板]低于正常对照组[（4.4±0.9）nmol/109个血小板],差异有统计学意义（t=-7.845;P〈0.01）;两亚型即约束型[（2.4±1.1）nmol/109个血小板]与暴食/清除型[（2.0±1.6）nmol/109个血小板]神经性厌食患者血小板5-HT浓度比较,差异无统计学意义（P〉0.05）。结论本研究结果支持神经性厌食患者5-HT能低下的假说;并提示约束型与暴食/清除型神经性厌食发病有着相同的5-HT机制。     

“区域化管理”+形成性评价在留学生生物化学教学中的运用

目的 本研究拟从专业课教师角度“解决”留学生学习生物化学过程中,因语言障碍引发的学习困难、被动学习等问题。方法 将80名留学生随机分成2组,试验组主要通过在教学中引入“区域化管理”模式,允许学生用母语或英语对精心设计的问题开展小组讨论,同时在课堂中增加随堂练习及开展阶段性测试,即引入形成性评价来督促学生学习及评估学生的学习效果,对照组则正常教学,最后通过考试卷面成绩及统计问卷调查数据等方式评价研究效果。采用SPSS 25.0进行Kruskal-Wallis H检验和Nemenyi检验。结果 27人（75.00%）的学生认为区域化分组讨论能使问题讨论得更深入;27人（75.00%）的学生不再觉得学习生物化学很难,甚至觉得容易;有近90.00%的学生对形成性评价模式进行了肯定,认为此模式对自己学习态度及行为产生了积极影响;另外,从学生卷面成绩看,试验组班级成绩中位数较同年其他班级（对照组）提高了36.94%。结论 “区域化管理”加形成性评价调动了学生学习的积极性,同时提高了学生的综合成绩,使学生学习行为有了明显的正向改变。     

新医科背景下《生物化学与分子生物学》混合式教学改革与实践

目的 探讨“课前同步小规模限制性在线课程（small private online course,SPOC）+课堂翻转+课后知识拓展”的混合式教学在《生物化学与分子生物学》理论教学中的应用效果。方法 选取齐齐哈尔医学院2020级临床医学、预防医学、药学类专业共951名学生作为教学改革研究组（试验组）,其课程依托自建慕课（massive open online course,MOOC）课程和中国大学MOOC资源,构建混合式教学,采用小班分组、案例驱动和多元化考核等改革方式,开展以案例和知识点交叉融合为主线的理论翻转教学活动;对照组为2019级临床医学、预防医学、药学类专业学生共847名,理论课实施传统教学。课程采取线下考核为主、线上考核为辅的方式进行评价,通过考试成绩、问卷调查、网络投票等方式收集反馈信息。采用SPSS 20.0进行统计学分析,组间比较采用t检验。结果 试验组学生期末总成绩得分高于对照组[（92.12±3.88）vs.（86.73±5.27）],差异有统计学意义（P<0.05）。问卷调查显示,试验组学生对混合式教学改革满意度较高,增加了学生参与、体验与分享等活动。2020级临床医学专业学生认为初步建立了临床思维（263人,92.61%）,熟悉了常见疾病的临床表现及发病机制（262人,92.25%）;2020级预防医学专业学生认为增强了为公众服务的意识（151人,93.21%）,培养了健康宣讲指导健康生活的能力（148人,91.36%）;2020级药学类专业学生认为掌握了疾病治疗药物的作用机制（138人,93.24%）,了解了临床合理用药（135人,91.22%）。结论 混合式教学实现了以学生为中心,激发了学生学习的兴趣和主动性,提高了学生的学习效果,在一定程度上提高了教学质量。     

不同检测方法在药物安全性评价试验中效果比较

目的 比较酶组化法、生化法及病理检测法在低分子量褐藻多糖硫酸酯(LMWF)安评试验中药物毒性反应的敏感性。方法 16只Beagle犬,雌雄各半,按体质量随机分为对照组,LMWF低、中、高［200、800、3000mg/(kg·d)］剂量组,每组4只,灌胃给药13 周。检测第1次给药前及末次给药后的动物血清生化指标。末次给药后,麻醉处死动物取肝脏,在肝脏相同位置取1cm3大小组织,速冻、切片及染色,进行酶组织化学检测。另取肝脏组织用4%中性甲醛溶液固定,石蜡包埋切片,HE染色,光学显微镜检查。结果 给药前和给药结束后,LMWF各给药组动物的血清生化指标与Veh组比较差异无统计学意义(P>0.05);光学显微镜观察,各给药组动物肝脏的组织形态并未发现明显病变;肝脏ATPase和SDH无论是定性观察还是定量分析,LMWF高剂量组给药酶活性下降明显,与对照组比较差异有统计学意义(P<0.05)。结论 酶组化法对毒物的敏感性要高于血清生化法及病理学法。     

磁处理水对培养液中某些生化指标的影响

为探讨不同磁场处理水对淋巴细胞转化率的影响,采用交变磁场和静磁场处理水配制细胞培养液,与蒸馏水配制的细胞培养液进行比较。各种培养液均在相同条件下培养72h后离心并分离淋巴细胞,结果2种磁处理水能显著增强淋巴细胞转化率和提高细胞培养液中K~+、Na~+、Ca~（2+）、Cl~-、MMS、BUN、葡萄糖的含量（P<0.01）,同时也能显著增强培养液中ALT、LDH的活性（P<0.01）。实验表明,磁处理水具有增强机体免疫功能和促进细胞物质能量代谢的作用。     

Glutathione peroxidase activity in rat lens and other tissues in relation to dietary selenium intake

Glutathione peroxidase (E.C. 1.11.1.9: glutathione: H₂O₂ oxidoreductase) activity and selenium concentration were measured in lenses of female rats and their offspring after long-term feeding of either a selenium-supplemented ($\text{0·1 parts}\text{10}{}^6$) or selenium-deficient ($\text{<}\text{0·02 parts}\text{10}{}^6$) diet. Long-term selenium deficiency decreased lens glutathione peroxidase activity in parent rats and their offspring to 15 and 14% respectively of supplemented controls. For comparison to lens, glutathione peroxidase was also measured in liver, heart, lung, erythrocytes, kidney, adrenal, testis, and brain of the offspring. Selenium deficiency caused the enzyme to decrease most dramatically in liver (to 0) and least in brain (to 62% of selenium supplemented controls). Although glutathione peroxidase in lens was lower than that in the other organs assayed, it was among the organs more sensitive to depletion caused by selenium deficiency. A short-term selenium deficiency of 8 weeks in newborn lambs had no effect on lens glutathione peroxidase, but the enzyme in organs such as liver was dramatically decreased. Therefore, an extensive period of selenium deficiency appears necessary to affect lens glutathione peroxidase activity, which probably relates to the relatively slow turnover and slow growth of the lens. The possible role of the seleno-enzyme, glutathione peroxidase, in the prevention of cataracts and the relationship of selenium to vitamin E and sulfur-containing amino acids in this regard are discussed.