特发性肺纤维化患者嗜酸粒细胞与肺功能相关性的研究

特发性肺纤维化(IPF)发病机制至今尚未完全清楚。大量研究结果表明,肺泡巨噬细胞、淋巴细胞和中性粒细胞等免疫细胞及其分泌的炎症介质在IPF的发病、进展方面起重要作用;临床上将IPF归为中性粒细胞型肺泡炎,强调了中性粒细胞在IPF中的作用。但是,近年来嗜酸粒细胞在间质性肺疾病(ILD)发病中所起的作用日益受到关注。一些研究发现嗜酸粒细胞的激活及其释放的嗜酸粒细胞阳离子蛋白(ECP)是引起肺间质纤维化的重要因素[1,2]。我们对32例IPF患者支气管肺泡灌洗液(BALF)中白细胞和肺通气功能、弥散功能[单次呼吸法一氧化碳弥散(DLCO)]…     

中性粒细胞在急性缺血性卒中病程中的作用及研究进展

炎性反应在急性缺血性卒中(AIS)的发生发展过程中起重要作用。中性粒细胞作为炎性反应的重要标志物之一,其在AIS发生后最先从外周血迁移入脑组织,并聚集在缺血区周围,通过细胞计数增加及释放细胞因子等方式参与炎性损伤及修复过程。该文从中性粒细胞的表型、所分泌细胞因子以及其与其他免疫细胞的相互关系等方面,对外周免疫细胞参与AIS的进展及其对静脉溶栓治疗的影响等进行了综述。     

粒细胞集落刺激因子与心血管疾病

近年来大量的研究表明骨髓干细胞能够促进心肌梗死后侧支循环的形成,加快血管损伤后内皮的修复.粒细胞集落刺激因子是一类血液生长因子,近来研究发现它可以动员骨髓干细胞,使它们归巢到梗死区域,复制、分化并促进心肌的修复.本文就粒细胞集落刺激因子在心血管疾病,包括心肌梗死、血管损伤后再狭窄和心力衰竭中的作用机制及应用进行综述.     

急性肾损伤肾小管上皮细胞修复的分子机制

近端小管上皮细胞凋亡或坏死是急性肾损伤(AKI)最常见的原因。各种损伤可诱导激活上皮细胞关键转录因子和上皮内再生因子,促进肾小管上皮细胞-间充质转化。肾小管上皮细胞与免疫细胞、间质细胞和内皮细胞之间复杂的分子交互作用可调节肾脏的修复。与公认的促炎、促纤维化机制不同,越来越多的研究表明存在促进损伤后肾脏修复的巨噬细胞、T细胞、B细胞亚群。在轻中度急性肾单位损伤区域,受损的肾小管上皮细胞可完全再生修复。重度损伤区域,再生过程受损失调,引起广泛的组织重塑和纤维化。     

粒细胞集落刺激因子动员骨髓内皮祖细胞促进损伤血管内皮修复

目的探讨大鼠颈动脉球囊损伤后粒细胞集落刺激因子动员对损伤血管内膜增殖和内皮修复的影响及其相关机制。方法36只雄性Wistar大鼠随机分为假手术组(n=12)、损伤 细胞因子组(n=12)和损伤 安慰剂组(n=12)。损伤 细胞因子组在球囊损伤后即刻腹腔注射粒细胞集落刺激因子[100μg/(kg.d)]直至术后2周,损伤 安慰剂组给予等量生理盐水注射,术后2周取血管段HE染色计算内膜/中膜面积比,免疫组织化学观察并计算增殖细胞核抗原阳性细胞比例,通过伊文氏蓝染色计算内皮修复率,血管匀浆检测一氧化氮释放量,用流式细胞术检测外周血CD34 VEGFR-2 双阳性细胞比例。结果与假手术组比较,损伤 安慰剂组血管内膜增殖明显,有较多增殖细胞核抗原阳性细胞,内皮修复不全,血管匀浆中一氧化氮释放量减少;与损伤 安慰剂组相比,损伤 细胞因子组内膜/中膜面积比和增殖细胞核抗原阳性细胞比例降低(分别为1.04±0.05比1.67±0.07和21.3%±5.1%比34.4%±6.1%,P<0.05),内皮修复率和一氧化氮释放量增加(分别为70.1%±4.6%比53.2%±3.8%和71.3±12.9μmol/L比56.7±10.8μmol/L,P<0.05);损伤 细胞因子组外周血CD34 VEGFR-2 双阳性细胞比例较损伤 安慰剂组明显上升(0.954%±0.076%比0.379%±0.052%,P<0.05)。结论粒细胞集落刺激因子明显增强血管损伤后内皮修复并减轻新生内膜增生,其机制可能涉及骨髓动员增加外周血内皮祖细胞比例。     

特发性嗜酸性粒细胞增多症伴多器官损害1例

<正>特发性嗜酸性粒细胞增多症(idiopathic hypereosinophilic syndrome,IHES)是一组病因不明的骨髓增生性疾病,其特征是持续且显著的外周血嗜酸性粒细胞增多和由于嗜酸性粒细胞浸润而对多个器官的炎性损伤,包括心脏、肺、皮肤、中枢神经系统和胃肠道,也有报道可出现静脉血栓栓塞症~([1-2])、膜性肾病~([3])、眼部表现及斜颈~([4-5])。临床表现复杂多样,取决于疾病的严重程度和终末器官受累的模式。在排     

中性粒细胞防御素与肺部疾病的研究进展

人中性粒细胞肽(human neutrophil peptides,HNPs)主要是由活化的中性粒细胞释放的阳离子多肽,因具有多种生物学特性而受到广泛关注.越来越多的研究证明,HNPs与中性粒细胞在中性粒细胞气道炎症中共同参与肺组织的损伤与修复.本文就HNPs的结构特点、生物学特性及功能、与中性粒细胞的相互关系、对肺上皮细胞的影响及其在中性粒细胞相关的炎症性肺疾病中的表达情况进行了综述,为临床研究提供新的方向.     

T细胞参与心肌I/R损伤的研究进展

心肌I/R损伤（MI/RI）是治疗心肌梗死过程中的并发症之一,中性粒细胞、巨噬细胞等固有免疫细胞引起的炎性反应是导致MI/RI的重要原因。众多免疫细胞如何在MI/RI中发挥作用是目前研究的热点问题。近年来,越来越多的研究表明T细胞在MI/RI中发挥重要作用。本文将阐述T细胞在MI/RI中的作用及机制的研究进展,并分析目前存在的问题及发展方向。     

T细胞参与心肌缺血/再灌注损伤的研究进展

心肌缺血/再灌注损伤(MI/RI)是治疗心肌梗死过程中的并发症之一,中性粒细胞、巨噬细胞等固有免疫细胞引起的炎性反应是导致MI/RI的重要原因。众多免疫细胞如何在MI/RI中发挥作用是目前研究的热点问题。近年来,越来越多的研究表明T细胞在MI/RI中发挥重要作用。本文将阐述T细胞在MI/RI中的作用及机制的研究进展,并分析目前存在的问题及发展方向。     

特发性嗜酸粒细胞增多综合征研究进展

特发性嗜酸粒细胞增多综合征是一种以嗜酸粒细胞增多伴靶器官损害为特征的异源性疾病,既往以排除性诊断和防治靶器官损害为主,新近研究显示酪氨酸激酶抑制剂伊马替尼可使部分患者获得完拿血液学缓解,并由此发现一由染色体缺失形成的融合基因FIPILI—PDGFRα。现将已有对特发性嗜酸粒细胞增多综合征的认识及FIPILI—PDGFRα对特发性嗜酸粒细胞增多综合,正诊断分类及治疗的意义作一综述。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

MUTATION FREQUENCY IN NURSES AND PHARMACISTS WORKING WITH CYTOTOXIC DRUGS

Individuals occupationally exposed to cytotoxic drugs may be at risk owing to the effects of these agents on DNA. As an index of DNA damage, in vivo mutations were measured in lymphocytes from 24 oncology nurses or pharmacists and 24 matched controls. Mutation frequency was significantly increased in exposed individuals and appeared to be related to duration of exposure. However, the overall magnitude of the increase was small and its biological significance remains to be determined.     

A single injection of adrenergic agonists enhances pineal melatonin production in Turkish hamsters

Abstract: The purpose of this study was to determine whether the pineal gland of Turkish hamsters (Mesocricetus brandti) responds to adrenergic agonists with an increase in melatonin production, and, if it does, whether the sensitivity of the pineal gland to agonists would differ throughout the dark phase. Adult Turkish hamsters weighing 110–210 g received a subcutaneous injection of isoproterenol (ISO, 1 mg/kg B.W.) or norepinephrine (NE, 1 mg/kg B.W.) at different times of night. Animals exposed to LD 16:8 responded to ISO or NE with increased pineal melatonin content only when injected at dawn, when endogenous melatonin is at basal or near-basal levels. When the 8 hr scotophase was entirely replaced with light, the responsiveness to ISO injections at dawn disappeared. In animals exposed to light from 30 min prior to injection to the time of sacrifice, ISO injections increased pineal melatonin content (P < 0.005, three-way ANOVA), which varied, depending on the specific time of injection (effect of time of night, P < 0.05, three-way ANOVA). These results demonstrate that (1) adrenergic agonists enhance the production of pineal melatonin in Turkish hamsters, (2) this stimulatory effect takes place late, but not early in the 8 hr scotophase, and (3) the adrenergic induction of pineal melatonin production in Turkish hamsters requires priming by darkness during the appropriate circadian phase.     

Immune effector mechanisms in malaria: An update focusing on human immunity

The past decade has witnessed dramatic decreases in malaria‐associated mortality and morbidity around the world. This progress has largely been due to intensified malaria control measures, implementation of rapid diagnostics and establishing a network to anticipate and mitigate antimalarial drug resistance. However, the ultimate tool for malaria prevention is the development and implementation of an effective vaccine. To date, malaria vaccine efforts have focused on determining which of the thousands of antigens expressed by Plasmodium falciparum are instrumental targets of protective immunity. The antigenic variation and antigenic polymorphisms arising in parasite genes under immune selection present a daunting challenge for target antigen selection and prioritization, and is a given caveat when interpreting immune recall responses or results from monovalent vaccine trials. Other immune evasion strategies executed by the parasite highlight the myriad of ways in which it can become a recurrent infection. This review provides an update on immune effector mechanisms in malaria and focuses on our improved ability to interrogate the complexity of human immune system, accelerated by recent methodological advances. Appreciating how the human immune landscape influences the effectiveness and longevity of antimalarial immunity will help explain which conditions are necessary for immune effector mechanisms to prevail.     

Secondary aortoduodenal fistula

Aorto-duodenal fistulae （ADF） are the most frequent aorto-enteric fistulae （80%）, presenting with upper gastrointestinal bleeding. We report the first case of a man with a secondary aorto-duodenal fistula presenting with a history of persistent occlusive syndrome. A 59-year old man who underwent an aortic-bi-femoral bypass 5 years ago, presented with dyspepsia and biliary vomiting. Computed tomography scan showed in the third duodenal segment the presence of inflammatory tissue with air bubbles between the duodenum and prosthesis, adherent to the duodenum. The patient was submitted to surgery, during which the prosthesis was detached from the duodenum, the intestine failed to close and a gastro-jejunal anastomosis was performed. The post-operative course was simple, secondary ADF was a complication （0.3%-2%） of aortic surgery. Mechanical erosion of the prosthetic material into the bowel was due to the lack of interposed retroperitoneal tissue or the excessive pulsation of redundantly placed grafts or septic procedures. The third or fourth duodenal segment was most frequently involved. Diagnosis of ADF was difficult. Surgical treatment is always recommended by explorative laparotomy. ADF must be suspected whenever a patient with aortic prosthesis has digestive bleeding or unexplained obstructive syndrome. Rarely the clinical picture of ADF is subtle presenting as an obstructive syndrome and in these cases the principal goal is to effectively relieve the mechanical bowel obstruction.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Married to M. tuberculosis: risk of infection and disease in spouses of smear-positive tuberculosis patients

Objectives To quantify the risk of infection and disease in spouses of tuberculosis patients and the extent to which intervention could reduce the risk in this highly exposed group. Methods We compared HIV prevalence, TB prevalence and incidence and tuberculin skin test (TST) results in spouses of TB patients and community controls. HIV‐positive spouses were offered isoniazid preventive therapy (IPT), and TST was repeated at 6, 12 and 24 months. Results We recruited 148 spouses of smear‐positive patients ascertained prospectively and 3% had active TB. We identified 203 spouses of previously diagnosed smear‐positive patients, 11 had already had TB, and the rate of TB was 2.4 per 100 person years(py) over 2 years (95% CI 1.15–5.09). 116 were found alive and recruited. HIV prevalence was 37% and 39% in the prospective and retrospective spouse groups and 17% in controls. TST was ≥10 mm in 80% of HIV negative and in 57% of HIV‐positive spouses ascertained retrospectively; 74% HIV negative and 62% HIV‐positive spouses ascertained prospectively, and 48% HIV negative and 26% HIV‐positive community controls. Of 54 HIV‐positive spouses, 18 completed 6‐month IPT. At 2 year follow‐up, 87% of surviving spouses had TST ≥10 mm and the rate of TB was 1.1 per 100 py (95% CI 0.34–3.29). Conclusions Spouses are a high‐risk group who should be screened for HIV and active TB. TST prevalence was already high by the time the spouses were approached but further infections were seen to occur. Uptake and adherence to IPT was disappointing, lessening the impact of short‐duration therapy.