大鼠肺泡巨噬细胞吞噬煤尘颗粒的实验研究

本实验用相差显微电影、溶酶体荧光定位和透射电镜等方法,研究了大鼠离体肺泡巨噬细胞吞噬煤尘的作用,并用二氧化矽和酵母菌作实验对照。结果表明,煤尘颗粒同二氧化矽类似,经过附着,迅速以吞噬体形式被摄入胞浆,而酵母菌呈典型的伪足包围和缓幔吞噬过程。实验证明,用吖啶橙作活细胞溶酶体定位是有效的。被标记的溶酶体发出强橙色荧光。当煤粒吞噬体进入胞浆后,常被多个溶酶体接触包围,形成次级溶酶体。电镜观察提示,煤尘可引起次级溶酶体膜的损害。     

人TH基因重组腺病毒的构建及生物学活性研究

将人酪氨酸羟化酶cDNA表达盒克隆于质粒型腺病毒载体p△Elsp1A，得到重组质粒pAd－TH。随后用脂质体法将重组质粒pAd－TH和拯救型腺病毒质粒pBHG11一起共转染293细胞，通过体内同源重组生成重组腺病毒AdCMVth，THcDNA重组进入腺病毒E1区并受CMV启动子控制。采用形态学、病毒核酸酶切和PCR／RT－PCR等方法进行鉴定正确。重组腺病毒滴度达到1010pfu／ml。初步结果表明，该重组腺病毒感染MN9D细胞后可使细胞内多巴胺水平增加1倍，显示出明显的TH生物学活性。提示TH重组腺病毒AdCMVth可作为高效的基因转移载体用于帕金森氏病基因治疗。     

Ⅱ期高血压病高胰岛素血症对血液粘度及血脂的影响

以２１例Ⅱ期高血压患者、２１例Ⅱ期高血压病高胰岛素血症患者及２０例正常人为研究对象，以全血比粘度、全血还原比粘度、血浆比粘度、红细胞压积及血浆甘油三酯、总胆固醇、高密度脂蛋白为指标；结果表明Ⅱ期高血压病患者全血比粘度、全血还原比粘度较正常人高，Ⅱ期高血压病高胰岛素血症患者亦较单纯高血压病患者进一步增高，同时其血浆甘油三酯较单纯高血压病患者增高，高密度脂蛋白降低．而血浆比粘度、红细胞压积、总胆固醇三组间无显著性差异。单纯高血压病患者与正常人组比较血脂无差异。因而认为高血压病患者的高胰岛素血症可使高血压病患者增高的血粘度进一步增高，且血粘度的增高主要是红细胞机能、代谢的改变所致。单纯高血压病患者血脂改变不明显，高血压病患者血脂的改变主要是由高胰岛素血症所致。     

Pentasomy 8q in therapy-related myelodysplastic syndrome due to cyclophosphamide therapy for fibrosing alveolitis

Trisomy 8/8q is a common cytogenetic event in myelocytic malignancies, ranging from myelodysplastic syndrome (MDS) to acute myelocytic leukemia (AML) to blastic transformation of chronic myelocytic leukemia. Isochromosome 8q results in the same gene dosage effect. Duplication of i(8q), resulting in pentasomy 8q, has been reported only in two cases of AML. A patient with fibrosing alveolitis on prolonged cyclophosphamide treatment developed therapy-related MDS. Karyotyping, FISH, and CGH analysis showed a duplicated i(8q) among other complex abnormalities. The clinical features of 11 cases of myelocytic leukemia with pentasomy and hexasomy 8/8q were summarized. Compared with trisomy and tetrasomy 8, significant features included reduced median survival (90 days), treatment refractoriness (even with transplantation), monocytic differentiation, trilineage dysplasia, and radiation or toxin exposure. Increasing copy numbers of chromosome 8/8q may therefore be a marker of advanced leukemic evolution, exposure to toxins, underlying myelodysplasia, and an overall poor prognosis.     

Novel multi-component nanopharmaceuticals derived from poly(ethylene) glycol, retro-inverso-Tat nonapeptide and saquinavir demonstrate combined anti-HIV effects

Background  

Current anti-AIDS therapeutic agents and treatment regimens can provide a dramatically improved quality of life for HIV-positive people, many of whom have no detectable viral load for prolonged periods of time. Despite this, curing AIDS remains an elusive goal, partially due to the occurrence of drug resistance. Since the development of resistance is linked to, among other things, fluctuating drug levels, our long-term goal has been to develop nanotechnology-based drug delivery systems that can improve therapy by more precisely controlling drug concentrations in target cells. The theme of the current study is to investigate the value of combining AIDS drugs and modifiers of cellular uptake into macromolecular conjugates having novel pharmacological properties.     

The role of mPer1 in morphine dependence in mice

Investigations using Drosophila melanogaster have shown that the circadian clock gene period can influence behavioral responses to cocaine, and the mouse homologues, mPer1 and mPer2, modulate cocaine sensitization and reward. In the present study, we applied DNAzyme targeting mPer1 to interfere the expression of mPer1 in CNS in mice and studied the role of mPer1 on morphine dependence. We found that the DNAzyme could attenuate the expression of mPer1 in CNS in mice. Mice treated with DNAzyme and morphine synchronously did not show preference to the morphine-trained side, whereas the control group did. In contrast, mice treated with DNAzyme after morphine showed preference to the morphine-trained side as well as the control group did. These results indicate that drug dependence seems to be influenced at least partially by mPer1, but mPer1 cannot affect morphine dependence that has been formed.     

Influence of Imidazole-Dipeptides on Cognitive Status and Preservation in Elders: A Narrative Review

The worldwide increase in the number of patients with dementia is becoming a growing problem, while Alzheimer’s disease (AD), a primary neurodegenerative disorder, accounts for more than 70% of all dementia cases. Research on the prevention or reduction of AD occurrence through food ingredients has been widely conducted. In particular, histidine-containing dipeptides, also known as imidazole dipeptides derived from meat, have received much attention. Imidazole dipeptides are abundant in meats such as poultry, fish, and pork. As evidenced by data from recent human intervention trials conducted worldwide, daily supplementation of carnosine and anserine, which are both imidazole dipeptides, can improve memory loss in the elderly and reduce the risk of developing AD. This article also summarizes the latest researches on the biochemical properties of imidazole dipeptides and their effects on animal models associated with age-related cognitive decline. In this review, we focus on the results of human intervention studies using supplements of poultry-derived imidazole dipeptides, including anserine and carnosine, affecting the preservation of cognitive function in the elderly, and discuss how imidazole dipeptides act in the brain to prevent age-related cognitive decline and the onset of dementia.     

A Multidisciplinary,Community-Based Program to Reduce Unplanned Hospital Admissions

ObjectivesTo evaluate the effect of Hospital Admission Risk Program (HARP) on unplanned hospitalization, bed days, and mortality of enrolled individuals and to evaluate the cost-effectiveness of HARP.DesignA retrospective longitudinal analysis of hospital administrative data.InterventionIndividuals at risk of hospitalization were provided with multidisciplinary, community-based care support managed by care coordinators including integrated care planning, education, monitoring, service linkages, and general practitioner liaison over 6-9 months.Setting and ParticipantsIndividuals who were enrolled into 1 of 8 HARP chronic disease management programs between July 1, 2017, and June 30, 2018, at the Royal Melbourne Hospital, Australia.MethodsHospital admissions between 18 months before and 18 months after HARP enrollment were analyzed. Total hospital costs were compared between 18 months before and 12 months after HARP enrollment.ResultsA total of 1553 individuals with a median age of 71 years (interquartile range 60-81), 63.4% males, were admitted to HARP. Both unplanned hospitalizations and bed days were reduced during the HARP intervention compared to within 3 months before enrollment in each of the HARP management programs. After the HARP intervention, cardiac coach, cardiac heart failure, chronic respiratory, diabetes comanagement, and medication management programs had higher hospitalizations and bed days than individuals’ baseline of at least 3 months before HARP enrollment. Individuals in cardiac heart failure and chronic respiratory management programs had a higher mortality rate than other HARP chronic disease management programs. Individuals in cardiac coach, diabetes comanagement, and medication management programs had lower hospital costs during the HARP intervention compared to within 3 months before HARP enrollment.Conclusions and ImplicationsHARP reduced unplanned hospitalization and bed days but did not return individuals’ hospital use to baseline before the intervention. The variations in mortality between HARP chronic disease management programs implies that condition-specific goals between programs is preferable.     

Waning Antibody Responses in Asymptomatic and Symptomatic SARS-CoV-2 Infection

We investigated the kinetics of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in 7 asymptomatic persons and 11 patients with pneumonia. The geometric mean titer of neutralizing antibodies declined from 219.4 at 2 months to 143.7 at 5 months after infection, indicating a waning antibody response.