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Todd M. Getz 《Transfusion and apheresis science》2019,58(1):12-15
Platelet transfusions are a life-saving medical intervention used for the treatment of thrombocytopenia or hemorrhage. Extensive research has gone into trying to understand how to store platelets prior to the transfusion event. Much has been learned about storage bag materials, synthetic solutions, and how temperature impacts platelet viability and function. While room temperature storage of platelets preserves 24-hour in vivo platelet recovery and survival there is a greater risk for bacterial growth. Therefore, cold storage of platelets has become attractive due to the reduction in potential bacterial proliferation and the maintenance of platelet function beyond 5 days of storage. Cold stored platelets, however, have their own set of challenges. Cold stored platelets become activated through several mechanisms. The morphological and molecular changes that occur due to cold exposure enhance their ability to participate in the hemostatic process at the cost of rapid clearance from circulation. This review focuses on the underlying mechanisms leading to cold platelet activation and the receptor modifications involved in platelet clearance. 相似文献
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目的 通过观察早产儿不同胎龄Toll样受体9(TLR9)的表达,探讨早产儿免疫功能低下的机制。方法 采集2010年7月至2014年6月在上海市嘉定区妇幼保健院产科出生的活产新生儿的脐血229份,按胎龄分为4组,28~31周组,31~34周组,34~37周组,≥37周组,采用流式细胞术和实时荧光定量PCR方法,分别检测其TLR9的蛋白和mRNA表达情况,了解其与胎龄之间的关系,并分析mRNA和蛋白表达间的相关性。结果 TLR9阳性细胞率在28~31周组,31~34周组,34~37周组,≥37周组分别为(15.93±6.23)%,(11.63±6.70)%,(13.66±6.88)%,(20.51±12.06)%;其在胎龄28~31周较高,至31~34周逐渐下降至最低,两组差异有统计学意义(P<0.05);34~37周后TLR9阳性细胞率表达逐渐升高,至≥37周达最高,两胎龄组比较,差异具有统计学意义(P<0.05)。31~37周间新生儿脐血TLR9阳性细胞率与胎龄呈正相关(r=0.273,P=0.006)。TLR9 mRNA表达在28~31周组,31~34周组,34~37周组,≥37周组分别为(4.95±3.44)%,(8.89±8.49)%,(13.91±10.92)%,(7.19±7.11)%;其在28~36周逐渐升高,与胎龄呈正相关(r=0.355,P< 0.001)。≥37周TLR9 mRNA表达量下降,该值虽高于28~31周,但差异无统计学意义(P>0.05)。相关性分析表明,同胎龄时期同样本新生儿的TLR9 mRNA和TLR9阳性细胞率之间存在负相关(r=-0.227,P=0.011)。结论 TLR9阳性细胞率和TLR9 mRNA表达在不同胎龄组新生儿间有差异,TLR9阳性细胞率表达在31~37周间随着胎龄的增加而增加,TLR9 mRNA在28~36周间随着胎龄的增加而增加。 相似文献
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Michael M Gezalian Luigi Mangiacotti Padmesh Rajput Nicklaus Sparrow Konrad Schlick Shouri Lahiri 《Journal of cerebral blood flow and metabolism》2021,41(4):693
Adrenoceptor and calcium channel modulating medications are widely used in clinical practice for acute neurological and systemic conditions. It is generally assumed that the cerebrovascular effects of these drugs mirror that of their systemic effects – and this is reflected in how these medications are currently used in clinical practice. However, recent research suggests that there are distinct cerebrovascular-specific effects of these medications that are related to the unique characteristics of the cerebrovascular anatomy including the regional heterogeneity in density and distribution of adrenoceptor subtypes and calcium channels along the cerebrovasculature. In this review, we critically evaluate existing basic science and clinical research to discuss known and putative interactions between adrenoceptor and calcium channel modulating pharmacotherapies, the neurovascular unit, and cerebrovascular anatomy. In doing so, we provide a rationale for selecting vasoactive medications based on lesion location and lay a foundation for future investigations that will define neuroprotective paradigms of adrenoceptor and calcium channel modulating therapies to improve neurological outcomes in acute neurological and systemic disorders. 相似文献
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MEMRI and tumors: a method for the evaluation of the contribution of Mn(II) ions in the extracellular compartment
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Eliana Gianolio Francesca Arena Enza Di Gregorio Roberto Pagliarin Martina Delbianco Gabriella Baio Silvio Aime 《NMR in biomedicine》2015,28(9):1104-1110
The purpose of the work was to set‐up a simple method to evaluate the contribution of Mn2+ ions in the intra‐ and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by “silencing” the relaxation enhancement arising from Mn2+ ions in the extracellular space. In vitro relaxometric measurements allowed assessment of the sequestering activity of DO2A (1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid) towards Mn2+ ions, as the addition of Ca‐DO2A to a solution of MnCl2 causes a drop of relaxivity upon the formation of the highly stable and low‐relaxivity Mn‐DO2A. It has been proved that the sequestering ability of DO2A towards Mn2+ ions is also fully effective in the presence of serum albumin. Moreover, it has been shown that Mn‐DO2A does not enter cell membranes, nor does the presence of Ca‐DO2A in the extracellular space prompt migration of Mn ions from the intracellular compartment. On this basis the in vivo, instantaneous, drop in SE% (percent signal enhancement) in T1‐weighted images is taken as evidence of the sequestration of extracellular Mn2+ ions upon addition of Ca‐DO2A. By applying the method to B16F10 tumor bearing mice, T1 decrease is readily detected in the tumor region, whereas a negligible change in SE% is observed in kidneys, liver and muscle. The relaxometric MRI results have been validated by ICP‐MS measurements. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
7.
《中国现代医生》2020,58(14):5-8
目的研究经导管动脉化疗栓塞(TACE)对原发性肝癌患者的疗效及中性粒细胞/淋巴细胞计数比(NLR)、血小板/淋巴细胞计数比(PLR)的影响。方法选择2015年6月~2019年1月我院接诊的原发性肝癌患者80例作为研究对象,采用随机数表法将患者分为两组,每组各40例。对照组予传统肝切除术治疗,观察组采用TACE治疗。对比两组治疗后的临床效果,NLR、PLR、癌胚抗原(CEA)、可溶性B7-H4、可溶性白细胞介素-2受体(sIL-2R)及并发症发生情况。结果治疗后,两组患者的总有效率分别为75.00%和52.50%,观察组高于对照组,差异有统计学意义(P0.05);治疗前,两组患者NLR、PLR水平对比,差异无统计学意义(P0.05);治疗后,患者NLR、PLR水平下降,观察组低于对照组,差异有统计学意义(P0.05);治疗前,两组患者CEA、B7-H4、sIL-2R水平对比,差异无统计学意义(P0.05);治疗后,两组患者CEA、B7-H4、sIL-2R水平下降,观察组低于对照组,差异有统计学意义(P0.05);两组患者并发症发生率分别为17.50%、40.00%,观察组低于对照组,差异有统计学意义(P0.05)。结论在原发性肝癌患者中使用TACE效果显著,可有效改善患者肿瘤标志物水平,减少并发症,值得推广应用。 相似文献
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Se-Jin Lee Adam Lehar Yewei Liu Chi Hai Ly Quynh-Mai Pham Michael Michaud Renata Rydzik Daniel W. Youngstrom Michael M. Shen Vesa Kaartinen Emily L. Germain-Lee Thomas A. Rando 《Proceedings of the National Academy of Sciences of the United States of America》2020,117(49):30907
Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in mice in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.Myostatin (MSTN) is a secreted signaling molecule that normally acts to limit skeletal muscle growth (for review, see ref. 1). Mice lacking MSTN exhibit dramatic increases in muscle mass throughout the body, with individual muscles growing to about twice the normal size (2). MSTN appears to play two distinct roles in regulating muscle size, one to regulate the number of muscle fibers that are formed during development and a second to regulate the growth of those fibers postnatally. The sequence of MSTN has been highly conserved through evolution, with the mature MSTN peptide being identical in species as divergent as humans and turkeys (3). The function of MSTN has also been conserved, and targeted or naturally occurring mutations in MSTN have been shown to cause increased muscling in numerous species, including cattle (3–5), sheep (6), dogs (7), rabbits (8), rats (9), swine (10), goats (11), and humans (12). Numerous pharmaceutical and biotechnology companies have developed biologic agents capable of blocking MSTN activity, and these have been tested in clinical trials for a wide range of indications, including Duchenne and facioscapulohumeral muscular dystrophy, inclusion body myositis, muscle atrophy following falls and hip fracture surgery, age-related sarcopenia, Charcot–Marie–Tooth disease, and cachexia due to chronic obstructive pulmonary disease, end-stage kidney disease, and cancer.The finding that certain inhibitors of MSTN signaling can increase muscle mass even in Mstn−/− mice revealed that the function of MSTN as a negative regulator of muscle mass is partially redundant with at least one other TGF-β family member (13, 14), and subsequent studies have identified activin A as one of these cooperating ligands (15, 16). MSTN and activin A share many key regulatory and signaling components. For example, the activities of both MSTN and activin A can be modulated extracellularly by naturally occurring inhibitory binding proteins, including follistatin (17, 18) and the follistatin-related protein, FSTL-3 or FLRG (19, 20). Moreover, MSTN and activin A also appear to share receptor components. Based on in vitro studies, MSTN is capable of binding initially to the activin type II receptors, ACVR2 and ACVR2B (also called ActRIIA and ActRIIB) (18) followed by engagement of the type I receptors, ALK4 and ALK5 (21). In previous studies, we presented genetic evidence supporting a role for both ACVR2 and ACVR2B in mediating MSTN signaling and regulating muscle mass in vivo. Specifically, we showed that mice expressing a truncated, dominant-negative form of ACVR2B in skeletal muscle (18) or carrying deletion mutations in Acvr2 and/or Acvr2b (13) have significantly increased muscle mass. One limitation of the latter study, however, was that we could not examine the consequence of complete loss of both receptors using the deletion alleles, as double homozygous mutants die early during embryogenesis (22). Moreover, the roles that the two type I receptors, ALK4 and ALK5, play in regulating MSTN and activin A signaling in muscle in vivo have not yet been documented using genetic approaches. Here, we present the results of studies in which we used floxed alleles for each of the type II and type I receptor genes in order to target these receptors alone and in combination in muscle fibers. We show that these receptors are functionally redundant and that signaling through each of these receptors contributes to the overall control of muscle mass. 相似文献
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《Transfusion and apheresis science》2020,59(5):102868
The novel coronavirus disease (COVID-19) has been declared a pandemic by the world health organization and to limit the spread of the disease, many countries in the world, including India, had enforced a lockdown. Despite no restriction over the platelet donation activities, plateletpheresis donors became apprehensive regarding the possible risk of spread of the COVID-19 during the platelet donation and in the hospital premises. Many of them started hesitating for platelet donations. With this, the blood center started having an acute shortage of platelets. Various confidence-building steps were implemented by the blood center to promote voluntary plateletpheresis. The blood center staff and individual donors were educated to prevent the spread of COVID-19. The donor organizations and plateletpheresis donors were informed about the steps to be taken by the blood center during the donation and necessary steps for the prevention of the possible spread of COVID-19. With the help of these measures, the confidence of the individual platelet donors and the donor organizations was restored in the blood center and regular plateletpheresis was continued. These measures may also be useful to other blood centers in the COVID-19 pandemic and this experience may be useful if a similar pandemic lockdown happens in the future. 相似文献