合欢皮中新皂甙的结构鉴定

从合欢皮(Albizziae cortex)的95%乙醇提取物的正丁醇萃取部分中分离得到3个新的三萜皂甙,用化学方法及¹H-和¹³C-NMR,DEPT,COSY,TOCSY,HMQC-COSY,HMQC-TOCSY,HMBC,NOESY等波谱方法鉴定其结构为:I(1个三萜,9个糖,2个单萜),命名为合欢皂甙(julibroside)J₁;II(1个三萜,8个糖,2个单萜),命名为合欢皂甙J_{2;II(1个三萜,9个糖,2个单萜),命名为合欢皂甙J3。}     

柴胡皂甙q及其甙元的结构鉴定

从小叶黑柴胡(Bupleurum smithii Wolffvar;parvifolium ShanetY.Li)的根中得到3个化合物,柴胡皂甙元A和Q及柴胡皂甙q。柴胡皂甙元Q和柴胡皂甙q为新化合物,根据理化性质和波谱分析,确定其结构分别为齐墩果烷-11,13(18)-二烯-3β,16β,23,28,30-五醇和3β,16β,23,28,3O-五羟基齐墩果烷-11,13(18)-二烯-3-O-β-D-吡喃葡萄糖基(1→6)-[α-L-吡喃鼠李糖基(1→4)]-β-D-吡喃葡萄糖甙。     

The economics of primary prevention of cardiovascular disease – a systematic review of economic evaluations

Background

Global resource needs estimation is a critical part of addressing the HIV/AIDS epidemic. To generate these estimates knowledge of costs and cost structures is required. The evidence base for costs of HIV prevention programmes is limited. Even less is known about the existence of economies scale and whether, as economic theory suggests, average costs form a 'u'-shaped curve as scale increases. Using an econometric analysis, this paper addresses this question by estimating marginal costs and economies of scale for HIV prevention programmes for vulnerable groups in Southern India with different levels of coverage.

Methods

Two hybrid translog-cost functions were estimated. First, expenditure data from 78 state-funded HIV prevention projects in Andhra Pradesh were used to explore the impact of scale, institutional history and price on costs; second, economic cost data from 16 commercial sex worker projects across Tamil Nadu and Andhra Pradesh were analysed to additionally assess the impact of the value of inputs not reported in expenditure data and location. Coefficient estimates were used to calculate marginal costs and economies of scale.

Results

The econometric model yielded a good fit (R² = 0.46, p < 0.001 and R² = 0.79, p < 0.001, for the expenditure and economic cost datasets, respectively). The economies of scale index was greater than 1 for both datasets and fell as coverage increased. Analysis of the expenditure data found economies of scale were not exhausted, with a 0.002% change in total cost for each extra person reached and an 11% difference in total cost between target group categories. Estimation using the economic cost data suggests a point of minimum efficient scale at around 1750–2000 people reached, a 0.03% change in total cost for each extra person reached, and 28% lower costs in Tamil Nadu than Andhra Pradesh.

Conclusion

Econometric analysis of these standardized datasets provides insights into how costs change with coverage, the impact of project location and nature of the project target group. The results demonstrate the importance of understanding the nature of the cost function when designing, budgeting and estimating resource requirements for scaling up coverage of HIV prevention projects.     

Integrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis

The aorta is the largest artery in the body, yet processes underlying aortic pathology are poorly understood. The arterial media consists of circumferential layers of elastic lamellae and smooth muscle cells (SMCs), and many arterial diseases are characterized by defective lamellae and excess SMCs; however, a mechanism linking these pathological features is lacking. In this study, we use lineage and genetic analysis, pharmacological inhibition, explant cultures, and induced pluripotent stem cells (iPSCs) to investigate supravalvular aortic stenosis (SVAS) patients and/or elastin mutant mice that model SVAS. These experiments demonstrate that multiple preexisting SMCs give rise to excess aortic SMCs in elastin mutants, and these SMCs are hyperproliferative and dedifferentiated. In addition, SVAS iPSC-derived SMCs and the aortic media of elastin mutant mice and SVAS patients have enhanced integrin β3 levels, activation, and downstream signaling, resulting in SMC misalignment and hyperproliferation. Reduced β3 gene dosage in elastin-null mice mitigates pathological aortic muscularization, SMC misorientation, and lumen loss and extends survival, which is unprecedented. Finally, pharmacological β3 inhibition in elastin mutant mice and explants attenuates aortic hypermuscularization and stenosis. Thus, integrin β3–mediated signaling in SMCs links elastin deficiency and pathological stenosis, and inhibiting this pathway is an attractive therapeutic strategy for SVAS.The normal arterial wall is histologically divided into three layers: (1) an inner single layer of endothelial cells (ECs), (2) the media with alternating circumferential layers of smooth muscle and elastic lamellae, and (3) an outer adventitial layer, which includes fibroblasts and connective tissue. A critical component of the massive burden of cardiovascular disease on human health is an excessive and ectopic accumulation of arterial smooth muscle cells (SMCs). Unfortunately, therapeutic options for cardiovascular pathologies are hindered by our limited understanding of mechanisms underlying this vascular hypermuscularization (Owens et al., 2004; Seidelmann et al., 2014).In diverse arterial diseases, such as atherosclerosis, restenosis, pulmonary hypertension, and supravalvular aortic stenosis (SVAS), excess SMCs are accompanied by defective elastic lamellae (Sandberg et al., 1981; Raines and Ross, 1993; Karnik et al., 2003). Elastin is a critical component of elastic lamellae, and heterozygous loss of function in the elastin gene (ELN) results in SVAS, a devastating human disease of excessively muscularized arteries (including the ascending and descending aorta; Curran et al., 1993; Li et al., 1998b; Pober et al., 2008). Major surgery is the only therapy for vessel obstruction in elastin arteriopathy. SVAS occurs as an isolated entity or more commonly as the major cause of morbidity in Williams-Beuren syndrome (WBS), which is caused by consecutive deletion of ∼26–28 genes, including ELN, on chromosome 7 (Pober et al., 2008). A mechanism linking elastin defects and hypermuscularization in SVAS or, for that matter, in any vascular disease is not delineated. Integrins are transmembrane receptors that link the extracellular matrix to the actin cytoskeleton and thus are candidates for mediating the effects of defective elastic lamellae on vascular smooth muscle; however, their role in elastin mutant arteriopathy has not been studied.Here, we demonstrate that excess SMCs in elastin mutant mice derive from multiple preexisting SMCs that proliferate, dedifferentiate, and migrate. Integrin β3 expression, activation, and signaling are up-regulated in the aortic media of these mice and SVAS patients and in SVAS induced pluripotent stem cell (iPSC)–derived SMCs. Additionally, our results indicate that enhanced β3-mediated signaling is crucial for SMC misalignment and hyperproliferation in elastin mutants, and genetic or pharmacological inhibition of β3 in elastin mutant mice attenuates aortic hypermuscularization and stenosis. Furthermore, reducing the dosage of Itgb3 (encoding β3) extends elastin-null survival; no prior interventions have increased the viability of elastin mutant mice. Hence, inhibiting integrin β3–mediated signaling in smooth muscle is an attractive pharmacological strategy for SVAS.     

Pediatric peripheral blood progenitor cell collection: haemonetics MCS 3P versus COBE Spectra versus Fresenius AS104

BACKGROUND: An increasing number of apheresis machines are becoming available for peripheral blood progenitor cell (PBPC) collection in children. STUDY DESIGN AND METHODS: At the Children's Hospital of Florence (Italy), three apheresis machines were evaluated: MCS 3P (Haemonetics) (10 procedures in 4 patients, aged 10–12 years, weight 23.5-64 kg), Spectra, (COBE) (8 procedures in 3 patients, aged 4–17 years, weight 19–59 kg), and AS104 (Fresenius) (24 procedures in 9 patients, aged 2–16 years, weight 13.6-60 kg). For PBPC quantitative analysis, CD34 cytofluorimetry was employed. Relevant variables analyzed included efficiency of CD34+ cell extraction and enrichment, mononuclear cell purity and red cell contamination of the apheresis components, and platelet count decreases after leukapheresis. RESULTS: No significant differences in CD34+ cell-extraction abilities were found. However, the AS104 provided consistently purer leukapheresis components in terms of mononuclear cell and CD34+ cell enrichment (441 +/− 59%, vs. 240 +/− 35% and 290 +/− 42% for MCS 3P and Spectra, respectively). Postapheresis platelet counts dropped the least with the AS104. The smallest patient who underwent apheresis with MCS 3P (the only machine working on discontinuous flow and hence with greater volume shifts) weighed 23.5 kg and tolerated the procedure well, with no signs of hemodynamic instability. No significant complications were observed. CONCLUSION: All machines seem to have comparable PBPC extraction efficiency, but the AS104 seems to give the component with the greatest PBPC enrichment. This feature might be relevant for further ex vivo cell processing (CD34+ cell selection, expansion, and so on).     

Recombinant human interleukin-3 stimulation of hematopoiesis in humans: loss of responsiveness with differentiation in the neutrophilic myeloid series

Recombinant human (rh) interleukin-3 (IL-3) stimulated the proliferation and differentiation of erythroid, granulocyte, macrophage, eosinophil (Eo), and mixed colonies as well as megakaryocytes from human bone marrow cells. rh IL-3 was a weaker stimulus than rh granulocyte-macrophage colony-stimulating factor (GM- CSF) for day 14 myeloid cell colonies. At day 7 of incubation, rh IL-3 stimulated a few G, M, and Eo clusters but no colonies. This loss of responsiveness of myeloid cells to rh IL-3 was accentuated with further differentiation of the cells. rh IL-3 stimulated very few or no clones after five-day incubation with enriched promyelocytes and myelocytes, whereas rh GM-CSF was an efficient stimulus. Responsiveness to rh IL-3 was completely lost in postmitotic mature neutrophils. Incubation of these cells with rh IL-3 did not result in enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) of tumor cells or superoxide anion production after stimulation with formyl-methyl-leucyl-phenylalanine (FMLP), although they could be stimulated by rh GM-CSF. In addition, preincubation of neutrophils with different concentrations of rh IL-3 failed to increase or decrease their response to rh GM-CSF. In contrast to neutrophils, mature Eos could be stimulated by rh IL-3 to kill antibody-coated tumor cells. These results show that cells of the neutrophilic myeloid series lose their responsiveness to h IL-3 as they differentiate and suggest that although h IL-3 may be an important therapeutic agent to use for hematopoietic regeneration in vivo, the lack of stimulation of mature neutrophil function makes it an unlikely sole candidate as adjunct therapy for treatment of infectious diseases.     

Preliminary results from the third flight of the Millimeter Anisotropy Experiment (MAX)

Preliminary results from the June 1991 flight of MAX are presented. Simultaneous observations were made in bands centered at 6, 9, and 12 cm-1 with a bolometric receiver operating at 300 mK. The experimental sensitivities are the highest reported at angular scales of 0.3 degrees to 1.0 degrees. Interstellar dust is observed to have an emissivity [symbol, see text] nu 1.4+/-0.3 and to correlate with the Infrared Astronomical Satellite (IRAS) 100- map. After removal of emission from interstellar dust, 1.3 hr of integration on a 6 degrees scan yields an upper limit of temperature difference Delta T/T < 2.6 x 10(-5) at a Gaussian autocorrelation function centered at 0.5 degrees. The experiment and data analysis are described.     

Massive hemoptysis: control by embolization of the thyrocervical trunk

A case of recurrent hemoptysis following bronchial artery embolization is presented. The bleeding was successfully controlled by embolization of the thyrocervical trunk.     

Incidence of complications following laparoscopic hernioplasty

Smaller individual series on the outcome of laparoscopic hernioplasty techniques have been reported. This study reports on the complications of 3,229 laparoscopic hernia repairs performed by the authors in 2,559 patients. The TAPP (transabdominal preperitoneal) technique was the most frequently performed: 1,944 (60%). The totally preperitoneal technique was performed 578 (18%) times. The IPOM (intraperitoneal onlay mesh) repair was performed 345 (11%) times. The plug-and-patch technique was used 286 (9%) times and simple closure of the hernia defect without mesh was used in 76 (2%) repairs. Overall, there were 336 (10%) complications: 17 (0.5%) major and 265 (8%) minor. There were 54 (1.6%) recurrences, with a mean follow-up of 22 months. The TAPP technique had 19 (1%) recurrences and 141 (7%) complications. There were four bowel obstructions in this subgroup from herniation of small bowel through the peritoneal closure and trocar sites. The totally preperitoneal technique had no recurrence and 60 (10%) complications. The IPOM group had 7 (2%) recurrences and 47 (14%) complications. The plug-and-patch technique had 26 (9%) recurrences and 24 (8%) complications. The simple closure of the internal ring had 2 (3%) recurrences and 10 (13%) complications. Laparoscopic hernioplasty is not without complications. Training, experience, and attention to technique will prevent some of these complications.Presented at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), Nashville, Tennessee, USA, 18–19 April 1994