Comparison of human skeletal myoblasts and bone marrow-derived CD133+ progenitors for the repair of infarcted myocardium

OBJECTIVES: The present study was designed as a face-to-face functional comparison of human skeletal myoblasts (SMs) and CD133(+) bone marrow-derived hematopoietic progenitors in an animal model of semichronic myocardial infarction. BACKGROUND: Compared with SMs, bone marrow-derived cells have the advantage of plasticity and might more effectively regenerate ischemic cardiac tissue. However, few data exist on the comparative efficacy of these two cell types in semichronic infarcts. METHODS: A myocardial infarction was created by coronary ligation in 32 nude rats. Ten days later, rats received in-scar injections of human SMs, CD133(+) progenitors, or culture medium. Left ventricular function was assessed before and one month after transplantation by echocardiography and pressure-volume loops. Immunofluorescence, polymerase chain reaction, and in situ hybridization were used to detect cells grafted in the hearts. RESULTS: One month after transplantation, left ventricular ejection fraction decreased by 8 +/- 4% in controls, whereas it increased by 7 +/- 3% in CD133(+)-grafted hearts (p = 0.0015 vs. controls) and further by 15 +/- 5% in SM-treated hearts (p = 0.008 vs. controls). Systolic indices yielded by pressure-volume loops paralleled these data. Engrafted myotubes were identified in all SM-treated hearts by immunofluorescence, whereas in CD133(+)-grafted hearts, few human cells were only detected by polymerase chain reaction. CONCLUSIONS: In the setting of postinfarction scars, the transplantation of bone marrow-derived CD133(+) progenitors improves cardiac function, but this benefit is not superior to that afforded by myogenic cells.     

Post-partum sacral fracture associated with heparin treatment

We report the case of a 19-year-old woman who consulted for low-back pain 3 weeks after her first delivery. This young woman had a personal history of protein C deficiency and was treated daily during her pregnancy with low-molecular-weight heparin. Her body mass index was 34 and she only gained 10 kg during her pregnancy. Since the delivery - which occurred without any complication - she had suffered from a gradually increasing right-buttock pain and limp. Magnetic resonance imaging (MRI) revealed a fracture of the right sacral ala. After analgesia and 1 month of home relative bed rest, the patient recovered her functional capacities. Regarding our patient, who had no potential clinical risk factors for osteoporosis, the causal effect of heparin is thus possible but not certain. This case report illustrates the fact that clinicians should have a high suspicion of pelvic fracture in post-partum women, even in very young ones, presenting sudden onset of low back and pelvic pain, especially when they have received heparin during pregnancy. MRI seems to be the key exam because it is able to detect and stage fractures or microfractures.     

Treatment responses in Asians and Caucasians with chronic hepatitis C infection

AIM：To conduct a multicentre retrospective review of virological response rates in Asians infected with genotype 1 chronic hepatitis C（CHC） treated with combination interferon and ribavirin and then to compare their responses to that among Caucasians.
METHODS：Asian patients infected with genotype 1 CHC treated at 4 Australian centres between 2001 to 2005 were identified through hospital databases.Baseline demographic characteristics,biochemical,virological and histological data and details of treatment were collected.Sustained virological responses（SVR） in this cohort were then compared to that in Caucasian subjects,matched by genotype,age,gender and the stage of hepatic fibrosis.
RESULTS：A total of 108 Asians with genotype 1 CHC were identified.The end of treatment response（ETR） for the cohort was 79% while the SVR was 67%.Due to the relatively advanced age of the Asian cohort,only sixty-four subjects could be matched with Caucasians.The ETR among matched Asians and Caucasians was 81% and 56% respectively（P=0.003）,while the SVR rates were 73% and 36%（P 〈0.001） respectively.This difference remained significant after adjusting for other predictive variables.
CONCLUSION： Genotype 1 CHC in Asian subjects is associated with higher rates of virological response compared to that in Caucasians.     

Aging and probabilistic learning in single- and multiple-cue tasks

The objective of the study was to examine some of the conditions under which elderly people are able to learn probabilistic inverse relationships and when this type of learning is no longer possible. Two kind of tasks were used: (a) two single-cue learning tasks with either direct or inverse relationships (the Single-Cue Probability Learning paradigm), and (b) three two-cue learning tasks, one with two direct relationships, one with a combination of direct and inverse relationships, and one with two inverse relationships (the Multiple-Cue Probability Learning paradigm). Four groups of participants were included in the study: young adults (18- to 25-year-olds), adults (40- to 50-year-olds), elderly people (65- to 74-year-olds), and very elderly people (75- to 90-year-olds). It was shown that (a) older adults are able to reject the direct relationship "default" hypothesis and select the inverse relationship hypothesis when outcome feedback contradicting the default hypothesis is given, and provided that the learning setting be a very simple one, involving only one cue; (b) some older adults are able to select the inverse relationship hypothesis provided that the learning setting be a simple one,involving only two inverse relationship cues; and (c) very few older adults are able to select the inverse relationship hypothesis when the learning setting is a complex one, involving two cues with both direct and inverse relationships with the criterion. These results led to the revision of the "gradual decrease of cognitive flexibility in older adults" hypothesis proposed by Chasseigne, Mullet, and Stewart (Acta Psychologicgrave;a, 103, 229-238, 1997).     

New thioredoxin targets in the unicellular photosynthetic eukaryote Chlamydomonas reinhardtii

Proteomics were used to identify the proteins from the eukaryotic unicellular green alga Chlamydomonas reinhardtii that can be reduced by thioredoxin. These proteins were retained specifically on a thioredoxin affinity column made of a monocysteinic thioredoxin mutant able to form mixed disulfides with its targets. Of a total of 55 identified targets, 29 had been found previously in higher plants or Synechocystis, but 26 were new targets. Biochemical tests were performed on three of them, showing a thioredoxin-dependent activation of isocitrate lyase and isopropylmalate dehydrogenase and a thioredoxin-dependent deactivation of catalase that is redox insensitive in Arabidopsis. In addition, we identified a Ran protein, a previously uncharacterized nuclear target in a photosynthetic organism. The metabolic and evolutionary implications of these findings are discussed.     

Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses

Mesenchymal stem cells (MSCs) suppress alloantigen-induced T-cell functions in vitro and infusion of third-party MSCs seems to be a promising therapy for graft-versus-host disease (GVHD). Little is known about the specificity of immunosuppression by MSCs, in particular the effect on immunity to pathogens. We have studied how MSCs affect T-cell responses specific to Epstein-Barr virus (EBV) and cytomegalovirus (CMV). We found that EBV- and CMV-induced proliferation and interferon- (IFN-) production from peripheral blood mononuclear cells (PBMCs) was less affected by third-party MSCs than the response to alloantigen and that MSCs had no effect on expansion of EBV and CMV pentamer-specific T cells. Established EBV-specific cytotoxic T cells (CTL) or CMV-CTL cultured with MSCs retained the ability to proliferate and produce IFN- in response to their cognate antigen and to kill virally infected targets. Finally, PBMCs from 2 patients who received MSCs for acute GVHD showed persistence of CMV-specific T cells and retained IFN- response to CMV after MSC infusion. In summary, MSCs have little effect on T-cell responses to EBV and CMV, which contrasts to their strong immunosuppressive effects on alloreactive T cells. These data have major implications for immunotherapy of GVHD with MSCs and suggest that the effector functions of virus-specific T cells may be retained after MSC infusion.     

Outcomes and risks of granulocyte colony-stimulating factor in patients with coronary artery disease.

OBJECTIVES: Cytokine mobilization of progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia. BACKGROUND: Patients with coronary artery disease (CAD) have low numbers of endothelial progenitor cells compared with healthy subjects. METHODS: Granulocyte colony-stimulating factor (G-CSF), 10 microg/kg/day for five days, was administered to 16 CAD patients. Progenitor cells were measured by flow cytometry; ischemia was assessed by exercise stress testing and by dobutamine stress cardiac magnetic resonance imaging. RESULTS: Granulocyte colony-stimulating factor increased CD34+/CD133+ cells in the circulation from 1.5 +/- 0.2 microl to 52.4 +/- 10.4 microl (p < 0.001), similar to the response observed in 15 healthy subjects (75.1 +/- 12.6 microl, p = 0.173). Indices of platelet and coagulation activation were not changed by treatment, but C-reactive protein increased from 4.5 +/- 1.3 mg/l to 8.6 +/- 1.3 mg/l (p = 0.017). Two patients experienced serious adverse events: 1) non-ST-segment elevation myocardial infarction (MI) 8 h after the fifth G-CSF dose, and 2) MI and death 17 days after treatment. At 1 month after treatment, there was no improvement from baseline values (i.e., reduction) in wall motion score (from 25.7 +/- 2.1 to 28.3 +/- 1.9, p = 0.196) or segments with abnormal perfusion (7.6 +/- 1.1 to 7.7 +/- 1.1, p = 0.916) and a trend towards a greater number of ischemic segments (from 4.5 +/- 0.6 to 6.1 +/- 1.0, p = 0.068). There was no improvement in exercise duration at 1 month (p = 0.37) or at 3 months (p = 0.98) versus baseline. CONCLUSIONS: Granulocyte colony-stimulating factor administration to CAD patients mobilizes cells with endothelial progenitor potential from bone marrow, but without objective evidence of cardiac benefit and with the potential for adverse outcomes in some patients.     

静脉麻醉在老年患者胃肠镜检查中的应用

胃肠镜检查时易引起恶心、呕吐、腹痛,使患者产生畏惧心理,而对伴有心肺脑血管疾病的老年患者,还可引起心律失常或心肌梗死.合理的麻醉能消除患者的恐惧心理,抑制恶心、呕吐、疼痛反应,从而稳定呼吸循环功能,预防相关并发症的发生,但老年患者对麻醉药物耐受性差,且多伴有心肺脑血管疾病,故麻醉胃肠镜检查存在一定风险.