Shedding of soluble ICAM-1 into the alveolar space in murine models of acute lung injury

Intercellular adhesion molecule-1 (ICAM-1; CD54) is an adhesion molecule constitutively expressed in abundance on the cell surface of type I alveolar epithelial cells (AEC) in the normal lung and is a critical participant in pulmonary innate immunity. At many sites, ICAM-1 is shed from the cell surface as a soluble molecule (sICAM-1). Limited information is available regarding the presence, source, or significance of sICAM-1 in the alveolar lining fluid of normal or injured lungs. We found sICAM-1 in the bronchoalveolar lavage (BAL) fluid of normal mice (386 +/- 50 ng/ml). Additionally, sICAM-1 was spontaneously released by murine AEC in primary culture as type II cells spread and assumed characteristics of type I cells. Shedding of sICAM-1 increased significantly at later points in culture (5-7 days) compared with earlier time points (3-5 days). In contrast, treatment of AEC with inflammatory cytokines had limited effect on sICAM-1 shedding. BAL sICAM-1 was evaluated in in vivo models of acute lung injury. In hyperoxic lung injury, a reversible process with a major component of leak across the alveolar wall, BAL fluid sICAM-1 only increased in parallel with increased alveolar protein. However, in lung injury due to FITC, there were increased levels of sICAM-1 in BAL that were independent of changes in BAL total protein concentration. We speculate that after lung injury, changes in sICAM-1 in BAL fluid are associated with progressive injury and may be a reflection of type I cell differentiation during reepithelialization of the injured lung.     

Generalising the Cinderella Effect to unintentional childhood fatalities

We investigated whether the repeatedly demonstrated increase in risk of child abuse and infanticide associated with living with a step parent generalized to cases of unintentional childhood fatal injury, the most common cause of death in children across the developed world. Reports were drawn from the Australian National Coroners' Information System (NCIS) on all cases of intentionally (n=32) and unintentionally (n=319) produced fatal injury in children aged under 5 years between 2000 and 2003. Even when using the most conservative possible analytic approach, in which all cases in which family type was unclear were classified as being from an ‘intact biological family’, step children under 5 years of age were found to be at significantly increased risk of unintentional fatal injury of any type, and of drowning in particular. Children from single-parented families were generally not found to be at significantly increased risk of intentional or unintentional fatal injury, while children who lived with neither of their biological parents were at greatest risk overall for fatal injury of any type.     

Stem-cell approaches for kidney repair: choosing the right cells

With the increasing rate of end-stage renal failure and limited alternatives for its treatment, stem cell (SC) therapy for kidney injury is urgently needed. Choosing the right SC type is the critical step in realizing the potential of this therapeutic approach. Four possible sources of SCs are envisioned for the development of this type of treatment: (i) bone-marrow-derived SCs (BMSCs), (ii) renal adult SCs, (iii) embryonic SCs and (iv) fetal renal SCs. We suggest that resident SCs recently identified in the Bowman's capsule of adult human kidneys might prospectively be the ideal cell type for treatment of both acute and chronic renal injury because they display the potential to differentiate into multiple types of renal cells. However, BMSCs also represent an attractive alternative, especially for the treatment of patients affected by acute renal failure.     

The role of placenta growth factor in the hyperoxia‐induced acute lung injury in an animal model

Prolonged exposure to hyperoxia leads to acute lung injury. Alveolar type II cells are main target of hyperoxia‐induced lung injury. However, the cellular and molecular mechanisms remain unknown. Here, we aimed to investigate the role of placental growth factor (PLGF) in hyperoxia‐induced lung injury. Using experimental hyperoxia‐induced lung injury model of neonatal rat and mouse lung epithelial type II cells (MLE‐12), we examined the levels of PLGF in bronchoalveolar lavage fluid and in the supernatants of MLE‐12 cells. Our results revealed that exogenous PLGF induced hyperoxia‐induced lung injury. Furthermore, PLGF triggered a shift of vinculin from insoluble to soluble cell fraction, similar to the observation under hyperoxia stimulation. Moreover, we observed significantly reduced phosphorylation of focal adhesion kinase and increased permeability in MLE‐12 cells treated with PLGF. These results suggest that PLGF triggers focal adhesion disassembly in alveolar type II cells via inhibiting the activation of focal adhesion kinase. Our findings reveal a novel role of PLGF in hyperoxia‐induced lung injury and provide a potential target for the management of hyperoxia‐induced acute lung injury. Copyright © 2014 John Wiley & Sons, Ltd.     

新型战伤急救止血剂体内抗菌活性的实验研究

目的:探讨新型战伤急救止血剂对家兔急性感染伤口的抗菌作用。方法:选用兔感染创面模型,分新型战伤止血剂、5A沸石、Quiclot和空白对照组对创面进行治疗,通过组织学观察、组织内细菌计数等方法对各组抗菌性能进行研究。结果:肉眼和组织学观察新型战伤急救止血剂治疗组动物模型伤口,炎症反应均小于其他各组;新型战伤急救止血剂治疗组织内细菌计数为104,比其他3组显著减少(P<0.01)。结论:新型战伤急救止血剂具有良好的体内抗菌性能。     

Association between the Number of Injuries Sustained and 12-Month Disability Outcomes: Evidence from the Injury-VIBES Study

Objective

To determine associations between the number of injuries sustained and three measures of disability 12-months post-injury for hospitalised patients.

Methods

Data from 27,840 adult (18+ years) participants, hospitalised for injury, were extracted for analysis from the Validating and Improving injury Burden Estimates (Injury-VIBES) Study. Modified Poisson and linear regression analyses were used to estimate relative risks and mean differences, respectively, for a range of outcomes (Glasgow Outcome Scale-Extended, GOS-E; EQ-5D and 12-item Short Form health survey physical and mental component summary scores, PCS-12 and MCS-12) according to the number of injuries sustained, adjusted for age, sex and contributing study.

Findings

More than half (54%) of patients had an injury to more than one ICD-10 body region and 62% had sustained more than one Global Burden of Disease injury type. The adjusted relative risk of a poor functional recovery (GOS-E<7) and of reporting problems on each of the items of the EQ-5D increased by 5–10% for each additional injury type, or body region, injured. Adjusted mean PCS-12 and MCS-12 scores worsened with each additional injury type, or body region, injured by 1.3–1.5 points and 0.5 points, respectively.

Conclusions

Consistent and strong relationships exist between the number of injury types and body regions injured and 12-month functional and health status outcomes. Existing composite measures of anatomical injury severity such as the NISS or ISS, which use up to three diagnoses only, may be insufficient for characterising or accounting for multiple injuries in disability studies. Future studies should consider the impact of multiple injuries to avoid under-estimation of injury burden.     

Application of the fourth universal definition of myocardial infarction in clinical practice

Abstract

Purpose: The Fourth Universal Definition of Myocardial Infarction (MI) has highlighted the different pathophysiological mechanisms that may lead to ischaemic and non-ischaemic myocardial injury and has emphasised that the diagnosis of myocardial infarction requires the presence of acute myocardial ischaemia in the setting of acute myocardial injury. This case based review intends to illustrate basic principles on how to apply this new, revised definition in clinical practice.

Methods and Results: The distinction between different types of MIs (type 1 or type 2) and the delineation of MI from acute non-ischaemic myocardial injury may be challenging in individual patients, which is illustrated by presenting and discussing real-life routine cases.

Conclusions: Type 1?MI is a consequence of coronary plaque rupture or erosion with intracoronary thrombus formation that is usually apparent on coronary angiography. Plausible triggering mechanisms causing myocardial oxygen supply/demand mismatch must be identified for the diagnosis of type 2?MI and its treatment should focus initially on management of the underlying disease attributable to acute myocardial ischaemia.     

Membrane attack complex of complement and neutrophils mediate the injury of acid aspiration.

A significant role for the alternative complement pathway in acid aspiration has been demonstrated by the observation that C3 genetic knockout mice are protected from injury. Utilizing C5-deficient mice, we now test the role of the terminal complement components in mediating injury. Lung permeability in C5-deficient mice was 64% less than in wild-type animals and was similar to wild-type mice treated with soluble complement receptor type 1, which gave a 67% protection. Injury was fully restored in C5-deficient mice reconstituted with wild-type serum. The role of neutrophils was established in immunodepleted wild-type animals that showed a 58% protection. Injury was further reduced (90%) with the addition of soluble complement receptor type 1, indicating an additive effect of neutrophils and complement. Similarly, an additional protection was noted in C5-deficient neutropenic mice, indicating that neutrophil-mediated injury does not require C5a. Thus acid aspiration injury is mediated by the membrane attack complex and neutrophils. Neutrophil activity is independent of C5a.     

Amino-terminal and midmolecule parathyroid hormone-related protein,phosphatidylcholine, and type II cell proliferation in silica-injured lung

Acute silica lung injury is marked by alveolar phospholipidosis and type II cell proliferation. Parathyroid hormone-related protein (PTHrP) 1-34 could have a regulatory role in this process because it stimulates phosphatidylcholine secretion and inhibits type II cell growth. Other regions of the PTHrP molecule may have biological activity and can also exert pulmonary effects. This study examined the temporal pattern for expression of several regions of PTHrP after silica lung injury and evaluated the effects of changes in expression on cell proliferation and lung phospholipids. Expression of all PTHrP regions fell at 4 days after injury. Reversing the decline in PTHrP 1-34 or PTHrP 67-86 with one intratracheal dose and four daily subcutaneous doses of PTHrP 1-34 or PTHrP 67-86 stimulated bronchoalveolar lavage disaturated phosphatidylcholine (DSPC) levels. Cell culture studies indicate that the peptides exerted direct effects on DSPC secretion by type II cells. Neither peptide affected type II cell proliferation with this dosing regimen, but addition of an additional intratracheal dose resulted in significant inhibition of growth, consistent with previous effects of PTHrP 1-34 in hyperoxic lung injury. These studies establish a regulatory role for PTHrP 1-34 and PTHrP 67-86 in DSPC metabolism and type II cell proliferation in silica injury. Growth inhibitory effects of PTHrP could interact with phospholipid stimulation by affecting type II cell numbers. Further studies are needed to explore the complex interactions of PTHrP-derived peptides and the type II cell response at various stages of silica lung injury.     

Injuries of the tarsometatarsal joints: treatment and outcome

Between January 2005 and May 2009, a total of 26 patients, 21 males and 5 females, were admitted for treatment of Lisfranc lesion. All patients were radiologically evaluated and classified according to the criteria proposed by Myerson: 5 (19.2%) patients had a type A injury, 2 patients (7.7%) presented with a type B1 injury, 17 (65.4%) sustained the most common type B2 injury and 1 (3.8%) patient suffered from a type C1 and C2 injury. Taking radiological and clinical findings in account, fifteen patients were elected for operative treatment and eleven patients were treated conservatively. According to type of fracture we established three groups; in group I metatarsal fracture was found in fourteen (53.9%) patients, group II with phalangeal fracture in three (11.5%) cases, whereas in group III nine (34.6%) patients sustained combined metatarsal, navicular and, most commonly, a cuneiform fracture. Using the American Orthopedic Foot and Ankle Society (AOFAS) midfoot scoring scale and SF-36 questionnaire, the functional outcome was assessed. The mean value for age distribution was 42.7 +/- 13.2 years and the mean follow up was 27.9 +/- 12.4 months. A p value < 0.005 was regarded as statistically significant for the analysis of the results. We found by means of SF 36 questionnaire a statistically significant difference in the role limitation due to existence of pain (p = 0.04) and poor general health (p = 0.013) in the group of patients that sustained combined foot fracture. The purpose of this study is to assess the treatment of Lisfranc injuries in our patients, according to SF36 and AOFAS criteria, clinical outcome was evaluated. In the group I the mean AOFAS score was 74.0 +/- 9.1 and in the group II it reached 72.0 +/- 5.2 signifying fair outcome! Poor outcome was present in the group III with mean AOFAS score 67.1 +/- 9.0. All unstable injuries require surgery. Clinical outcome is highly dependent on the restoration of normal anatomic alignment.     

棉花耐害补偿临界指标及其应用的探讨

棉花耐害补偿反应可归纳为三种动态类型：1)不足补偿动态反应型;2)完全——不足补偿动态反应型;3)超越——完全——不足补偿动态反应型。其临界指标的建立及其应用可优化棉花病虫害综防决策．以研究害虫防治决策为例,剖析了利用害虫自然种群,人为改变害虫自然种群、人为地接放一定虫量与人工损害模拟等不同测定棉花耐害补偿能力方法的利弊。并探讨改进措施．分析论述了不同量化棉花耐害补偿能力的方法,并就棉花耐害补偿临界指标的建立及其意义作了探讨．棉花耐害补偿临界描标在棉田生态系统有害生物综合治理中可用于指导防治决策或直接用于防治决策,有着十分广阔的应用前景．最后就棉花耐害补偿临界指标及其应用的研究方向及有关问题作了讨论。     

Parathyroid hormone-related protein response to hyperoxic lung injury

Parathyroid hormone-related protein (PTHrP) is a growth inhibitor for alveolar type II cells. Type II cell proliferation after lung injury from 85% oxygen is regulated, in part, by a fall in lung PTHrP. In this study, we investigated lung PTHrP after injury induced by >95% oxygen in rats and rabbits. In adult rats, lung PTHrP rose 10-fold over controls to 6,356 +/- 710 pg/ml (mean +/- SE) at 48 h of hyperoxia. Levels fell to 299 +/- 78 pg/ml, and staining for PTHrP mRNA was greatly reduced at 60 h (P < 0.05), the point of most severe injury and greatest pneumocyte proliferation. In adult rabbits, lung PTHrP peaked at 3,289 +/- 230 pg/ml after 64 h of hyperoxia with 24 h of normoxic recovery and then dropped to 1,629 +/- 153 pg/ml at 48 h of recovery (P < 0.05). Type II cell proliferation peaked shortly after the fall in PTHrP. In newborn rabbits, lavage PTHrP increased by 50% during the first 8 days of hyperoxia, whereas type II cell growth decreased. PTHrP declined at the LD(50), concurrent with increased type II cell division. In summary, lung PTHrP initially rises after injury with >95% hyperoxia and then falls near the peak of injury. Changes in PTHrP are temporally related to type II cell proliferation and may regulate repair of lung injury.     

Diphosphatidylglycerol in experimental acute alveolar injury in the dog

Acute alveolar injury closely resembling that seen in humans was induced in dogs by subcutaneous injection of N-nitroso-N-methylurethane. Necrosis of alveolar epithelial cells was observed during early injury. Proliferation of immature epithelial cells which began during early injury and became massive after peak injury was followed by their differentiation to mature type II cells during recovery. Quantities of diphosphatidylglycerol (DPG) and of phosphatidylglycerol (PG) in alveolar lavage and in post-lavage lung tissue were measured. An increase in tissue DPG coincided with a sharp decrease in tissue and lavage PG during early injury. DPG was not detectable in the lavage. During late recovery, tissue DPG increased threefold over controls. This increase was accompanied by persistence of a 50% decrease in tissue PG and 83% decrease in lavage PG. Biosynthesis of DPG and PG in isolated lung mitochondria demonstrated that DPG was formed from PG in the presence of CDP-diglyceride. These findings suggest that the low level of PG in the surfactant complex during acute alveolar injury is due to increased turnover of PG to DPG in the lung.     

Inhalation injury caused by the products of combustion.

Inhalation injury results from a type of chemical burn (tracheobronchitis) of the respiratory tract. When this injury occurs in patients with serious cutaneous burns the mortality is exceedingly high- 48% to 86%. The injury can be divided into three types according to the level at which the damage occurs; upper airway, major airway and terminal airway. The early signs and symptoms may be complicated by carbon monoxide poisoning. The patient''s condition usually follows a staged progression that is proportional to the extent and severity of the tracheobronchitis. Indirect laryngoscopy, bronchoscopy, scintiscanning of the lung with xenon 133 and serial analysis of arterial blood gases are useful diagnostic techniques. Treatment must be expeditious, and it depends on the severity of the injury. The prophylactic use of antibiotics and steroids is contraindicated.     

Injury recovery of foodborne pathogens in high hydrostatic pressure treated milk during storage

Bacteria are expected to be injured or killed by high hydrostatic pressure (HHP). This depends on pressure levels, species and strain of the microorganism and subsequent storage. Injured bacteria may be repaired which could affect the microbiological quality of foodstuffs with an important safety consideration especially in low acid food products. In this study two Gram-positive (Listeria monocytogenes CA and Staphylococcus aureus 485) and two Gram-negative (Escherichia coli O157:H7 933 and Salmonella enteritidis FDA) relatively pressure resistant strains of foodborne pathogens were pressurized at 350, 450 and 550 MPa in milk (pH 6.65) and stored at 4, 22 and 30 degrees C. The results of shelf life studies indicated two types of injury, I1 and I2, for all the pathogens studied. It is obvious that I2 type injury is a major injury and after its repair (I2 to I1), the cells can form colonies on non-selective but not on selective agar. The formation of colonies on both selective and non-selective agar occurs only after full recovery of injury (I1 to AC). The results presented in this study show that even if injured cells are not detected immediately after HHP treatment, I2 type injury could be potentially present in the food system. Therefore, it is imperative that shelf life studies must be conducted over a period of time for potential repair of I2 type injury either to detectable injury (I1) or to active cells (AC) to ascertain microbiological safety of low acid food products.     

A proposed tolerance criterion for diffuse axonal injury in man.

The head injury criterion (HIC) is currently the government-accepted head injury indicator. The HIC is not injury-specific, does not relate to injury severity, nor does it take into account variations in the brain mass or load direction. This report focuses on one type of inertial brain injury, diffuse axonal injury (DAI), and utilizes animal studies, physical model experiments, and analytical model simulations to determine the kinematics of DAI in the subhuman primate and to scale these results to man. A human injury tolerance for moderate to severe DAI, which includes the influences of rotational loads and brain mass, is proposed.     

Isolated capitellum humeri fractures in adults

From 2003 through 2009 we treated 35 patients who suffered from an isolated capitellum humerus fracture whom we treated with osteosynthesis. Patients who presented with concomitant fractures were not included. Thirty-four patients were categorized as Type I (Hahn-Steinthal) while one patient was Type IV (McKee). We describe the mechanism of injury and compared our results with works available in the literature. The average age of our patients was 38.6 years which was much younger than many articles about this type of injury found in the literature. The ratio of women to men in our study was 20:15. The surgical treatment was performed with various methods including: Kirschner wires, AO screws, Herbert screws and TwinFix screws. We discuss type of injury, days after injury operative treatment is performed, type of osteosynthesis used, the surgical approaches used for our treatment of capitellum humeri fractures, possible complications and our postoperative treatment. Results at the conclusion of treatment were excellent. Range of motion, shown in detail for each patient, was measured preoperatively, 1 month and 3 months postoperatively. We concluded that the major factors in successful treatment are how quickly the surgical treatment is performed after injury and early postoperative rehabilitation.     

Role of diminished epithelial GM-CSF in the pathogenesis of bleomycin-induced pulmonary fibrosis

Evidence derived from human and animal studies strongly supports the notion that dysfunctional alveolar epithelial cells (AECs) play a central role in determining the progression of inflammatory injury to pulmonary fibrosis. We formed the hypothesis that impaired production of the regulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) by injured AECs plays a role in the development of pulmonary fibrosis. To test this hypothesis, we used the well-characterized model of bleomycin-induced pulmonary fibrosis in rats. GM-CSF mRNA is expressed at a constant high level in the lungs of untreated or saline-challenged animals. In contrast, there is a consistent reduction in expression of GM-CSF mRNA in the lung during the first week after bleomycin injury. Bleomycin-treated rats given neutralizing rabbit anti-rat GM-CSF IgG develop increased fibrosis. Type II AECs isolated from rats after bleomycin injury demonstrate diminished expression of GM-CSF mRNA immediately after isolation and in response to stimulation in vitro with endotoxin compared with that in normal type II cells. These data demonstrate a defect in the ability of type II epithelial cells from bleomycin-treated rats to express GM-CSF mRNA and a protective role for GM-CSF in the pathogenesis of bleomycin-induced pulmonary fibrosis.     

The allograft defines the type of rejection (acute versus chronic) in the face of an established effector immune response

Transplanted organs fail due to either acute or chronic rejection. The prevailing view is that the nature or magnitude of the recipient's immune response to donor Ags determines the type of rejection. In variance with this view, we show in this study that the status of the graft itself plays a dominant role in defining the type of rejection even in the face of an established alloimmune response. Using adoptive transfer mouse models in which the graft is exposed to a constant number of effector lymphocytes, we found that newly transplanted heart allografts are rejected acutely, while healed-in allografts undergo chronic rejection. Acute rejection of healed-in allografts was largely recapitulated by subjecting the grafts to ischemia-reperfusion injury similar to that present in newly transplanted organs. Ischemia-Reperfusion injury altered the outcome of rejection by enhancing the accumulation of effector T cells within the graft. The accumulation of effector T cells in the graft was dependent on the presence of both ischemia-reperfusion injury (inflammation) and alloantigens. These findings demonstrate that the graft plays a dominant role in shaping the outcome of rejection by controlling the trafficking of effector T cells.     

新型战伤急救止血剂体内抗菌活性的实验研究

目的：探讨新型战伤急救止血剂对家兔急性感染伤口的抗菌作用。方法：选用兔感染创面模型,分新型战伤止血剂、5A沸石、Quiclot和空白对照组对创面进行治疗,通过组织学观察、组织内细菌计数等方法对各组抗菌性能进行研究。结果：肉眼和组织学观察新型战伤急救止血剂治疗组动物模型伤口,炎症反应均小于其他各组;新型战伤急救止血剂治疗组织内细菌计数为104,比其他3组显著减少（P〈0.01）。结论：新型战伤急救止血剂具有良好的体内抗菌性能。