Functional lung imaging with synchrotron radiation: Methods and preclinical applications

Many lung disease processes are characterized by structural and functional heterogeneity that is not directly appreciable with traditional physiological measurements. Experimental methods and lung function modeling to study regional lung function are crucial for better understanding of disease mechanisms and for targeting treatment. Synchrotron radiation offers useful properties to this end: coherence, utilized in phase-contrast imaging, and high flux and a wide energy spectrum which allow the selection of very narrow energy bands of radiation, thus allowing imaging at very specific energies. K-edge subtraction imaging (KES) has thus been developed at synchrotrons for both human and small animal imaging. The unique properties of synchrotron radiation extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and also to map regional lung ventilation, perfusion, inflammation and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. This review summarizes synchrotron radiation imaging methods and overviews examples of its application in the study of disease mechanisms in preclinical animal models, as well as the potential for clinical translation both through the knowledge gained using these techniques and transfer of imaging technology to laboratory X-ray sources.     

Threat calls in alliance formation by members of a captive group of Japanese monkeys

The vocal behavior of threat calls was investigated in a captive group of Japanese monkeys (Macaca fuscata fuscata). The vocalizations were heard most often when they undertook winner-support during triadic agonistic interactions. The likelihood of call emission in support of the winner was affected by the attributes of the participants, and not by the types of agonistic behavior. The calls were emitted by intermediate ranking animals frequently in support of high ranking animals and in support of females. The calling behavior of winner-supporters appears to advertise the partner and distant group members of their support for reciprocation in the near future.     

Latency of cathepsin B secreted by human colon carcinoma cells is not linked to secretion of cystacin C and is relieved by neutrophil elastase

The lysosomal cystein proteinase cathepsin B is shown to be secreted by ten human colon carcinoma cell lines and to accumulate in culture media as a latent enzyme. The cell lines also secrete a physiological inhibitor of cathepsin B, cystatin C. A significant correlation was found between secretion of the latent enzyme and the inhibitor (r = 0.755, P < 0.01). The aim of the present study was to modulate the respective secretion of the two antagonists to test whether or not latency of cathepsin B was due to the concomitant secretion of the inhibitor. SW480 colon carcinoma cells were treated with the acidotropic agent ammonium chloride, phorbol 12-myristate 13-acetate, and the inflammatory cytokines TGF-β, TNF-α, and IL-1β. Ammonium chloride significantly increased latent cathepsin B levels without affecting the constitutive secretion of cystatin C. Phorbol 12-myristate 13-acetate induced a 4- to 5-fold increase in secreted latent cathepsin B, but did not alter significantly the accumulation of cystatin C in media. The cytokines, TGF-β, TNF-α, and IL-1β, had no major effect on the expression of these two antagonists. Latent cathepsin B released from human carcinoma cells could be efficiently activated by neutrophil elastate at neutral pH. It is concluded that latent cathepsin B is a true proenzyme rather than an enzyme-inhibitor comples. In addition, our data from neutrophil elastate activation experiments indicate that a proteolytic system for activation of the tumor cell-secreted latent enzyme may exist in vivo.     

Bioacoustic analysis of frog calls from northeast India

Mating calls of three frog species abundant in northeast IndiaRana tigerina,Rana cyanophlyctis andRana limnocharis were recorded in the fields of Assam and Meghalaya during their breeding season (July-August, 1991). The calls were analysed for their temporal and spectral characters. They were species specific, with distinct call duration and call period, number of pulses per call and interpulse interval, and dominant frequency and frequency domain. A comparison of the mating calls ofRana cyanophlyctis with those of the siblingRana ehrenbergi from Yemen showed differences in their temporal and spectral characters, supporting the suggestion that these two species are distinct species, rather than subspecies of the same species. Differences in the temporal and spectral pattern were found in the mating calls of morphologically alike specimens ofRana limnocharis, indicating that the present morphotypeRana limnocharis in northeast India is composed of several species.     

Temporal Association Between Pulmonary Inflammation and Antioxidant Induction Following Hyperoxic Exposure of the Preterm Guinea Pig

The time course and nature of the pulmonary inflammatory and antioxidant responses, both during and after hyperoxic-induced acute lung injury were studied in the preterm guinea pig. Three-day preterm (65 days gestation) guinea pigs were randomly exposed to either 21% O₂ (control) or 95% O₂ (hyperoxia) for 72 hours. All pups were then maintained in ambient conditions for up to a further 11 days, during which time lung damage was monitored. In animals exposed to hyperoxia, evidence of acute lung injury and inflammation was characterized by a marked increase in microvascular permeability and elevated numbers of neutrophils in bronchoalveolar lavage fluid. Protein concentration, elastase-like activity and elastase-inhibitory capacity in lavage fluid were at a maximum at the end of the 72 hours hyperoxic exposure. Four days later, all values had returned to control levels. In contrast, increased numbers of neutrophils, macrophages and lymphocytes were recovered in the lavage fluid during this early recovery period. Coinciding with the influx of inflammatory cells, there was a significant increase in glutathione peroxidase, manganese superoxide dismutase and catalase activities in immature lung. Lung copper/zinc superoxide dismutase activity remained unchanged during both experimental periods. The strong temporal relationship between the influx of inflammatory cells to the lung and the induction of pulmonary antioxidant enzyme defences suggests that a common mechanism underlies both responses. These findings have led us to regard inflammation in the hyperoxic-injured immature lung as a beneficial event and not, as previously suggested, as part of the injurious process.     

Differences in preference for species-specific female calls between acoustically experienced and acoustically naive maleRibautodelphax planthoppers (Homoptera: Delphacidae)

Males of the planthopper Ribautodelphax imitanswere exposed to playbacks of either conspecific or heterospecific (R. imitantoides)female calls during their development from egg to adult, and thereafter these, as well as naive males,were offered a two- way choice between these calls. Males of all treatments approached the conspecific call significantly more often. However, males primed by the conspecific call chose the heterospecific call almost four times less often than did males primed by heterospecific calls or naive males, thus showing that the preference for conspecific calls can be partly learned. Males primed by heterospecific calls performed very similarly to completely naive males, suggesting that the signal recognition mechanism is much less sensitive to heterospecific calls than to conspecific calls. Males with experience of the conspecific female call tended to take more time to reach the call source in the trials than both other types of males. The evolutionary implications of these findings are discussed.     

Current status and prospects of basic research and clinical application of mesenchymal stem cells in acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a common and clinically devastating disease that causes respiratory failure. Morbidity and mortality of patients in intensive care units are stubbornly high, and various complications severely affect the quality of life of survivors. The pathophysiology of ARDS includes increased alveolar–capillary membrane permeability, an influx of protein-rich pulmonary edema fluid, and surfactant dysfunction leading to severe hypoxemia. At present, the main treatment for ARDS is mechanical treatment combined with diuretics to reduce pulmonary edema, which primarily improves symptoms, but the prognosis of patients with ARDS is still very poor. Mesenchymal stem cells (MSCs) are stromal cells that possess the capacity to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as the umbilical cord, endometrial polyps, menstrual blood, bone marrow, and adipose tissues. Studies have confirmed the critical healing and immunomodulatory properties of MSCs in the treatment of a variety of diseases. Recently, the potential of stem cells in treating ARDS has been explored via basic research and clinical trials. The efficacy of MSCs has been shown in a variety of in vivo models of ARDS, reducing bacterial pneumonia and ischemia-reperfusion injury while promoting the repair of ventilator-induced lung injury. This article reviews the current basic research findings and clinical applications of MSCs in the treatment of ARDS in order to emphasize the clinical prospects of MSCs.     

不同病情急性呼吸窘迫综合征患者血清铁蛋白、血管生成素样蛋白4、降钙素原与白蛋白比值的变化及对预后的评估价值

摘要 目的：探讨不同病情急性呼吸窘迫综合征（ARDS）患者血清铁蛋白、血管生成素样蛋白4（ANGPTL4）、降钙素原与白蛋白比值（PAR）的变化及对预后的评估价值。方法：选取2019年3月至2022年6月四川大学华西第四医院重症医学科收治的109例ARDS患者,根据氧合指数（PaO₂/FiO₂）将患者分为轻度组（200 mmHg＜PaO₂/FiO₂≤300 mmHg,38例）、中度组（100 mmHg＜PaO₂/FiO₂≤200 mmHg,42例）、重度组（≤100 mmHg,29例）。检测所有ARDS患者血清铁蛋白、ANGPTL4水平及PAR,根据患者入院后28 d内生存状况将其分为存活组（69例）、死亡组（40例）。多因素Logistic回归分析ARDS患者入院后28 d内死亡的危险因素。受试者工作特征（ROC）曲线分析血清铁蛋白、ANGPTL4、PAR评估ARDS患者预后的预测价值。结果：重度组血清铁蛋白、ANGPTL4、降钙素原及PAR高于中度组和轻度组（P＜0.05）,血清白蛋白水平低于中度组和轻度组（P＜0.05）。死亡组血清铁蛋白、ANGPTL4、降钙素原及PAR高于存活组（P＜0.05）,血清白蛋白水平低于存活组（P＜0.05）。高SOFA评分、高PAR及血清铁蛋白、ANGPTL4水平升高是 ARDS患者入院28 d内死亡的危险因素（P＜0.05）。联合血清铁蛋白、ANGPTL4、PAR三项指标预测ARDS患者预后的曲线下面积为0.867,高于单独指标预测的0.775、0.727、0.776。结论：ARDS患者血清铁蛋白、ANGPTL4水平及PAR增高与病情加重以及预后不良有关,联合检测三项指标在ARDS患者预后评估中具有较高价值。     

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ABSTRACT

In most mammals, adults produce relatively low frequency vocalizations compared to those of juveniles. This rule is not maintained however at least in four species of ground squirrels, whose juveniles call at the adult's fundamental frequency. These findings have been obtained however with separate sets of juveniles and adults and no data is available concerning the ontogeny linked to these differences. Here we analyze the acoustic structure of alarm calls of the same Yellow Spermophilus fulvus and Speckled S. suslicus ground squirrel individuals, recorded as pups and as adults after hibernation. We found the fundamental frequencies of adults within the same frequency ranges as those of pups, in spite of the significant difference in body mass. In ground squirrels, severing the relationship between body size and call frequency removes some vocal cues to age. We discuss some functional hypotheses advanced to explain manipulations with fundamental frequencies in ground squirrels and other animals, and suggest the lack of data for discussing the mechanisms of such vocal tuning.     

合并慢性气道疾病的ARDS临床特征及预后影响因素研究

目的:探讨急性呼吸窘迫综合征(ARDS)合并慢性气道疾病患者的临床特征及影响预后的因素。方法:167例ARDS患者根据并发症发生情况分为对照组(单纯性ARDS组,A组,n=39)及观察组(ARDS合并慢性气道疾,B组,n=49,C组,n=41,D组,n=38),比较各组患者一般情况、临床特征、生化指标、治疗方式及预后状况,通过logistic回归分析ARDS合并慢性气道疾病患者预后的影响因素。结果:观察组(B、C、D组)年龄、中性粒细胞、IL-6、IL-8、TNF-α、白蛋白、pro-BNP、乳酸、氧合指数、住院时间、住院费用与对照组(A组)比较差异有统计学意义,P0.05;128例ARDS合并慢性气道疾病患者中死亡76例,好转52例,病死率59.38%;单因素分析结果显示,观察组(B、C、D组)患者中临床结局好转患者与死亡患者比较,白细胞、淋巴细胞、CRP、TNF-α、IL-8、降钙素、肌酐、pro-BNP、氧合指数、住院费用、机械通气时间、抗生素数量差异有统计学意义,P0.05;通过多因素logistic回归分析发现肌酐是影响ARDS合并慢性气道疾病的潜在危险因素,氧合指数为保护因素,P0.05。结论:ARDS合并慢性气道疾病的能量代谢紊乱程度可能较单纯ARDS加重,且两者炎性特征不同。肌酐、氧合指数是影响ARDS合并慢性气道疾病的重要影响因素。