Tumor necrosis factor-alpha (TNF-alpha) potently enhances in vitro macrophage production from primitive murine hematopoietic progenitor cells in combination with stem cell factor and interleukin-7: novel stimulatory role of p55 TNF receptors

Tumor necrosis factor-alpha (TNF-alpha) is a bifunctional regulator of hematopoiesis, and its cellular responses are mediated by two distinct cell surface receptors. TNF-alpha generally inhibits the growth of primitive murine hematopoietic progenitor cells (Lin-Scal+) in response to multiple cytokine combinations, and the p75 TNF receptor is essential in signaling such inhibition. In the present study we show the reverse phenomenon in that TNF-alpha on the same progenitor cell population in combination with stem cell factor (SCF) and interleukin-7 (IL-7) through the p55 TNF receptor can recruit additional progenitors to proliferate. In contrast, TGF-beta 1, another bifunctional regulator of hematopoietic progenitor cell growth, completely blocked SCF plus IL- 7-induced proliferation. TNF-alpha increased the number of responding progenitors, as well as the size of the colonies formed. The synergistic effects of TNF-alpha were seen at the single cell level, suggesting that its effects are directly mediated. Finally, whereas SCF plus IL-7 promoted primarily granulopoiesis, the addition of TNF-alpha switched the differentiation toward the production of almost exclusively macrophages.     

Echocardiography detection of fetal ventricular aneurysm: A report of three cases

From March 2007 to September 2009, we have screened with echocardiography a total of 6,502 pregnant women for fetal heart disease. We found three cases of fetal ventricular aneurysm. The relatively large size of the aneurysm in these three cases was clearly visible under standard four‐chamber view. Two were right ventricular aneurysms arisen from the ventricular free wall, and both showed characteristics of true aneurysm with a thin wall and a large communication with the ventricular chamber. Color Doppler showed passive movement of aneurysm during right ventricle contraction. The third case was a large left ventricular aneurysm outpouching from a small opening of the left ventricular wall close to the apical region. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43 :257–261, 2015     

Genetic testing for familial hypercholesterolaemia: practical and ethical issues

Coronary artery disease (CAD) has a strong genetic component, but is also greatly influenced by environmental factors such as diet and smoking, and disorders such as diabetes mellitus and hypertension. This interaction makes prediction of CAD risk generally difficult. However, in familial hypercholesterolaemia (FH), risk of early CAD is considerably increased by the mutation of a single gene, and genetic testing may be appropriate. We summarize current knowledge concerning DNA-based tests in the identification and management of FH, and propose specific recommendations for genetic testing and further research. The major value of DNA tests for FH is in genetic tracing programs to identify and treat affected individuals. DNA testing is appropriate for: (a) diagnosis of FH when physical signs or family history are equivocal or absent (important given the increased risk of CAD associated with FH compared to other hypercholesterolaemias); (b) detection of a mutation causing FH in immediate family members (particularly children) where there is a family history of premature CAD. A positive DNA-based test for a mutation is especially useful in children, in whom plasma lipid levels may not be diagnostic. Current clinical practice is to test relatives for raised cholesterol. Testing for mutation carriers in distant relatives, although feasible, is not currently recommended. Research projects should now be started to address two issues: (i) whether genetic tests for FH better predict clinical outcome than does measurement of plasma lipid levels; (ii) whether genetic testing for FH confers overall benefit both to the patient and their relatives, and to the NHS. Answers to these questions will guide the subsequent development and implementation of genetic tests for CAD risk in general, if and when the considerably more complex genetic causes of CAD are identified.      

Prestorage white cell reduction in saline-adenine-glucose-mannitol red cells by use of an integral filter: evaluation of storage values and invivo recovery

BACKGROUND : Prestorage white cell (WBC) reduction in blood components may decrease the incidence of adverse reactions and improve component quality. A bottom-and-top system with an integral third-generation WBC- reduction filter has been studied. STUDY DESIGN AND METHODS : Whole blood was collected from 30 healthy donors: from 20 by using a blood container system with an integral filter and from 10 controls by using a standard blood container system. Ten test units were buffy coat- depleted, stored for 72 hours at 4 degrees C, and then filtered, while an additional 10 test units were buffy coat-depleted and filtered at room temperature within 8 hours of collection. All units were stored at 4 degrees C for 42 days and sampled weekly. RESULTS : The mean WBC content of the 72-hour, 4 degrees C units was 0.33 × 10(6), that of the room-temperature units was 2.6 × 10(6), and that of the buffy coat- depleted controls was 460 × 10(6) (p < 0.0005). No significant differences were found among lactate, glucose, sodium, potassium, and plasma hemoglobin levels in the three groups. ATP and 2,3 DPG levels were significantly better preserved in control units than in 72-hour, 4 degrees C units (p = 0.016 and p = 0.032, respectively), but not better than in the room-temperature units. Significant differences were observed between pH values in filtered units and both groups of test units (p = 0.016). In biologic terms however, these differences were small. Red cells from an additional eight healthy volunteer donors were processed by an 8-hour room-temperature method and stored for 35 days. Studies in vivo 24-hour recovery of autologous red cells were performed by transfusing a radiolabeled (51Cr plus 131I-albumin) aliquot after 35 days' storage. Good recovery (mean > 80%) was found by both the single- and double-isotope-label methods. Recovery was significantly greater when calculated by the single-isotope method (p = 0.02). CONCLUSION : The combination of buffy coat removal and filtration in the blood container system with an integral filter achieved effective WBC reduction (> or = 3 log10 reduction from whole blood) without biologically significant detriment to in vitro or in vivo storage values.     

脐血间充质干细胞体外培养方法的改良及其成骨分化能力

目的:采用两种改良方法体外分离培养脐血间充质干细胞,并观察其成骨分化能力。方法:实验于2006-05/09在上海交通大学医学院附属第九人民医院骨与关节中心细胞实验室完成。①所用28份脐血标本由复旦大学医学院附属妇产科医院提供,取自足月健康顺产新生儿,产妇和家属均书面同意,实验经医学伦理委员会批准。②采集28份脐血标本,50～90mL/份,枸橼酸抗凝。采集后12h内密度梯度离心法分离出单个核细胞,接种于100mm×20mm培养皿中,细胞浓度为1×1010L-1,置于含体积分数为0.1胎牛血清的α-MEM培养液中原代培养,5～7d后半量换液,后每隔3～4d全量换液一次。③细胞贴壁后,分两组予以改良培养。改良1组10份,当培养皿底圆形巨核细胞融合、梭形成纤维样细胞脱落时将细胞悬液移入新的培养皿中培养;改良2组18份,待培养皿底圆形巨核细胞渐渐占据优势时,将培养基更换为含体积分数为0.15小牛血清的α-MEM,当圆形巨核细胞大部脱落后换回含体积分数为0.1胎牛血清的α-MEM培养基。成纤维样细胞融合至80%～90%时胰酶消化,按1∶2或1∶3传代培养。④显微镜下观察脐血间充质干细胞的形态。取第5代脐血间充质干细胞,采用流式细胞仪测定细胞免疫表型,以碱性磷酸酶法检测成骨分化能力。结果:①28份脐血间充质干细胞中,共20份原代培养中出现贴壁细胞(改良1组6份,改良2组14份),其中13份培养出能融合且可稳定传代的成纤维样细胞(改良1组4份,改良2组9份),成功率46.4%。②原代培养5～7d后贴壁细胞呈梭形成纤维样细胞和圆形巨核细胞。改良1组与2组于原代培养5周可见成纤维样细胞集落,细胞形态与骨髓间充质干细胞相似,呈较均一的长梭形,传至22代形态无明显变化。③可强烈表达CD29、CD105等间充质干细胞表面标志,而不表达CD34、CD45和CD106等造血干细胞和内皮细胞标志。④成骨诱导1周,脐血间充质干细胞可分化为成骨细胞,碱性磷酸酶染色呈阳性。结论:脐血中存在的单个核细胞经过改良培养后,可提高脐血间充质干细胞的培养成功率。脐血间充质干细胞具有与其他来源的单个核细胞类似的表型及成骨分化潜能,且易于体外扩增、传代稳定。     

循环抗阻训练干预12周后中老年绝经后妇女体质指标及血糖和血脂的变化

目的:观察循环抗阻训练对绝经后妇女体质的影响。方法:调查于2005-03/12在邵阳学院运动康复中心进行。年龄50～65岁,自然绝经1年以上的绝经后妇女。未经激素替代治疗,身体基本健康,不吸烟,无心脑血管疾病、糖尿病,所有受试者试验前进行常规体检及辅助检查,未见异常。血总胆固醇在6.50mmol/L以下,三酰甘油在2.50mmol/L以下,体脂率在35%以下。所有受试者保持平时的饮食习惯及一般的体力活动。不重复随机数法分为抗阻训练组和对照组两组,每组12人。两组实验前的各指标比较无明显差异。抗阻训练组应用器械和在训练机上进行躯干及上下肢大肌群的练习。每次运动包括3个循环,每1循环包括12节运动,每节运动包括在30～45s内做8次收缩,各节运动间休息15～30s,每个循环间休息2min。训练强度:为1次收缩最大负荷的80%。每周二、四、六训练,3次/周。每4周测1次最大收缩力,以监测训练进程和确定新的运动负荷。实验期间严格进行医务监督并遵循循序渐进原则。12周的抗阻训练后测定身高、体质量、心率、血压、腰围、臀围、体脂率、最大吸氧量、血糖、血脂。结果:24名绝经后妇女均进入结果分析。①抗阻训练组训练后的腰围、臀围、体脂率、安静收缩压与训练前及对照组比较,均显著降低或减少[训练后:(74.4±5.5)cm,(92.0±5.0)cm,(25.7±3.4)%,(105.4±17.0)mmHg;训练前:(76.8±5.2)cm,(94.1±5.1)cm,(27.4±3.5)%,(112.7±14.0)mmHg;对照组:(76.1±4.6)cm,(93.0±5.2)cm,(27.1±3.7)%,(114.0±15.1)mmHg,P<0.01,P<0.05]。握力和背肌力较训练前及对照组明显增加[训练后:(27.9±2.5),(64.7±3.6)kg;训练前:(23.6±2.5),(61.6±4.2)kg;对照组:(23.9±1.6),(59.2±3.3)kg,P<0.01]。②抗阻训练组训练后三酰甘油较训练前及对照组下降[(1.42±0.13),(1.63±0.14),(1.63±0.19)mmol/L,P<0.01,P<0.05],低密度脂蛋白胆固醇较训练前降低[(3.14±0.44),(3.26±0.56),(3.10±0.47)mmol/L,P<0.05],高密度脂蛋白胆固醇较训练前及对照组显著升高[(1.44±0.24),(1.26±0.25),(1.23±0.23)mmol/L,P<0.01,P<0.05]。结论:循环抗阻训练可安全有效地改善绝经后妇女的体质,是预防和治疗冠心病的有效措施。     

Effect of radiotherapy and hyperthermia on the tumor accumulation of HPMA copolymer-based drug delivery systems.

Copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) are prototypic and well-characterized polymeric drug carriers that have been broadly implemented in the delivery of anticancer therapeutics. In an attempt to improve the tumor accumulation of HPMA copolymer-based drug delivery systems, their in vivo application was combined with radiotherapy and hyperthermia. As the effects of radiotherapy and hyperthermia were considered to depend significantly on the tumor model used, we first analyzed the accumulation of two differently sized HPMA copolymers in three different types of tumors, based on the syngeneic Dunning rat prostate carcinoma model. Subsequently, in these three models, the effects of different doses of radiotherapy and hyperthermia on the tumor accumulation of 31 kDa poly(HPMA), 65 kDa poly(HPMA) and 28 kDa poly(HPMA)-GFLG-doxorubicin were evaluated. It was found that the polymeric drug delivery systems accumulated effectively in all three tumor models. In addition, as opposed to hyperthermia, radiotherapy was found to improve the concentrations of the copolymers independent of the tumor model used. Based on these findings, we conclude that radiotherapy is an effective means for increasing the tumor accumulation of (polymeric) drug delivery systems, and we propose that the combination of carrier-based chemotherapy with radiotherapy holds significant potential for improving the treatment of advanced solid malignancies.     

Sustained efficacy and tolerability with vardenafil over 2 years of treatment in men with erectile dysfunction

This randomised, double-blind study assessed the long-term efficacy and tolerability of vardenafil 10 and 20 mg in men with erectile dysfunction (ED). A total of 566 men who completed an initial 12-month treatment period entered a 12-month extension. In these men, both doses of vardenafil produced improvement in scores for the 'erectile function' Domain of the International Index of Erectile Function, evident from week 4 and maintained through 2 years. Sexual Encounter Profile diary responses indicated that following treatment, penetration was achieved on 92-94% of attempts and erections that lasted long enough for successful intercourse were achieved on 87-89% of attempts. In response to the General Assessment Question, 90-92% of patients reported improved erections with vardenafil. Most treatment-emergent events were mild and transient with no cardiovascular safety concerns. These results support the long-term efficacy, reliability and tolerability of vardenafil 10 and 20 mg in men with ED.     

Optimierung der Risiko- und Krisenkommunikation von Regierungen,Behörden und Organisationen der Gesundheitssicherung – Herausforderungen in lang anhaltenden Krisen am Beispiel der COVID-19-Pandemie

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Die COVID-19-Pandemie illustriert die besondere Bedeutung von Risiko- und Krisenkommunikation. Behörden und Politik stehen...     

Oral type II collagen treatment in early rheumatoid arthritis. A double-blind,placebo-controlled,randomized trial

Objective. To investigate the efficacy of oral type II collagen in the treatment of early rheumatoid arthritis (RA). Methods. Ninety patients with RA (disease duration ⩽3 years) were treated for 12 weeks with oral bovine type II collagen at 1 mg/day (n = 30) or 10 mg/day (n = 30) or with placebo (n = 30), in a double-blind randomized study. Results. There was no significant difference between the 3 groups in terms of response to treatment. However, we observed a higher prevalence of responders in the type II collagen-treated groups: 7 responders in the 10-mg type II collagen group and 6 in the 1-mg group, versus 4 in the placebo group. Furthermore, 3 patients in the 10-mg type II collagen group and 1 patient in the 1-mg type II collagen group, but no patients in the placebo group, had very good response. A total of 14 patients had to be withdrawn from the study: 2 because of side effects (nausea) and 12 because of lack of efficacy. Conclusion. Only a minority of patients responded to treatment with oral type II collagen. These results justify further efforts to identify which patients will have a good response to such therapy.