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1.
2.

Objective

Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.

Methods

Heart transplants were performed after 6 hours of cold ischemic storage. Recipient pigs were randomized to treatment with or without HTS (7.5% NaCl) before cardiopulmonary bypass (CPB). Using a myograft apparatus, coronary artery endothelial-dependent (Edep) and -independent (Eind) relaxation was assessed. LV performance was determined using pressure-volume loop analysis. Pulmonary interleukin (IL)-2, IL-6, and tumor necrosis factor (TNF)-α expression was measured.

Results

Weaning from CPB and LV performance after transplantation were improved in HTS-treated animals. Successful weaning from CPB was greater in the HTS-treated hearts (8 of 8 vs 2 of 8; P < .05). Mean LV functional recovery was improved in the HTS-treated animals, as assessed by preload recruitable stroke work (65 ± 10% vs 27 ± 10%; P < .001) and end-systolic elastance (55 ± 7% vs 37 ± 4%; P < .001). Treatment with HTS resulted in improved Edep (mean maximum elastance [Emax], 56 ± 5% vs 37 ± 7%; P < .001) and Eind (mean Emax%, 77 ± 6% vs 52 ± 4%; P < .001) vasorelaxation compared with control. Pulmonary expression of IL-2, IL-6, and TNF-α increased following transplantation, whereas HTS therapy attenuated IL production (P < .001). Transplantation increased plasma TNF-α levels and LV TNF-α expression, whereas HTS prevented this up-regulation (P < .001).

Conclusions

Recipient HTS pretreatment preserves allograft vasomotor and LV function, and HTS therapy limits CPB-induced injury. HTS may be a novel recipient intervention to prevent graft dysfunction.  相似文献   
3.

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Methods

In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).

Results

After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).

Conclusions

This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.  相似文献   
4.
In the marine environment, sulfate ions and chloride ions are abundant. Therefore, sulfate attack and chloride ion attack are common failure forms of marine concrete. Mg–Al hydrotalcite is a layered bimetallic hydroxide, which can be used as guest molecular adsorbent. In this experiment, we synthesized Mg–Al hydrotalcite, and the crystal state, surface morphology, and composition of this adsorbent were investigated by modern micro-analysis technology. Mg–Al hydrotalcite was added into the prepared target ion solution, to explore the influence of various factors on the adsorption performance of Mg–Al hydrotalcite, and then calcined Mg–Al hydrotalcite was added into cement paste, to study the mechanical properties and durability of the paste samples. The experimental results show that the optimum conditions for adsorption of chloride ions by calcined Mg–Al hydrotalcite are an adsorption time of 4 h, temperature of 35 °C, LDO (calcined Mg-Al hydrotalcite) dosage of 3.5 g/L, and a pH of 8. The adsorption effect of sulfate ion is best when the adsorption time is 6 h, the temperature is 35 °C, the dosage of LDO is 4 g/L, and the pH = 8. The optimal adsorption conditions of calcined Mg–Al hydrotalcite for chloride ion and sulfate ion are not completely the same, and the adsorption of these two ions in mixed solution shows competitive adsorption. Compared with the common paste specimens without Mg–Al hydrotalcite, the mechanical properties and deformation properties of cement specimens can be significantly improved by adding Mg–Al hydrotalcite.  相似文献   
5.
A high salt diet (HSD) is among the most important risk factors for many diseases. One mechanism by which HSD aggravates cerebral ischemic injury is independent of blood pressure changes. The direct role of HSD in inflammation after cerebral ischemia is unclear. In this research, after twenty-one days of being fed a high salt diet, permanent focal ischemia was induced in mice via operation. At 12 h and 1, 3 and 5 days postischemia, the effects of HSD on the lesion volume, microglia polarization, aldose reductase (AR) expression, and inflammatory processes were analyzed. We report that in mice, surplus dietary salt promotes inflammation and increases the activation of classical lipopolysaccharide (LPS)-induced microglia/macrophages (M1). This effect depends on the expression of the AR protein in activated microglia after permanent middle cerebral artery ligation (pMCAL) in HSD mice. The administration of either the AR inhibitor Epalrestat or a p38-neutralizing antibody blocked the polarization of microglia and alleviated stroke injury.In conclusion, HSD promotes polarization in pro-inflammatory M1 microglia by upregulating the expression of the AR protein via p38/MAPK, thereby exacerbating the development of ischemia stroke.  相似文献   
6.
7.

Background

Various trajectories for lung function and bronchial hyper-reactivity (BHR) from early childhood to adulthood are described, including puberty as a period with excessive lung growth. Bronchiolitis in infancy may be associated with increased risk of developing chronic obstructive pulmonary disease, but the development of respiratory patterns during puberty is poorly characterized for these children. We aimed to study the development and trajectories of lung function and BHR from 11 to 18 years of age in children hospitalized for bronchiolitis in infancy.

Methods

Infants hospitalized for bronchiolitis at the University Hospitals in Stavanger and Bergen, Norway, during 1997-1998, and an age-matched control group, were included in a longitudinal follow-up study and examined at 11 and 18 years of age with spirometry and methacholine provocation test (MPT). The MPT data were managed as dose-response slope (DRS) in the statistical analyses. Changes in lung function and DRS from 11 to 18 years of age were analyzed by generalized estimating equations, including interaction terms.

Results

z-scores for forced vital capacity (FVC), forced expiratory volume in first second (FEV1), FEV1/FVC ratio, and DRS were not different from 11 to 18 years of age in both the post-bronchiolitis and the control group. The trajectories from 11 to 18 years did not differ between the two groups. BHR at age 11 was independently associated with asthma at age 18.

Conclusion

Children hospitalized for bronchiolitis had stable predicted lung function and BHR from 11 to 18 years of age. The lung function trajectories were not different from controls.
  相似文献   
8.
PurposeTo experimentally characterize a microwave (MW) ablation applicator designed to produce directional ablation zones.Materials and MethodsUsing a 14-gauge, 2.45-GHz side-firing MW ablation applicator, 36 ex vivo bovine liver ablations were performed. Ablations were performed at 60 W, 80 W, and 100 W for 3, 5, and 10 minutes (n = 4 per combination). Ablation zone forward and backward depth and width were measured and directivity was calculated as the ratio of forward to backward depth. Thirteen in vivo ablations were performed in 2 domestic swine with the applicator either inserted into the liver (80 W, 5 min, n = 3; 100 W, 5 min, n = 3; 100 W, 10 min, n = 2) or placed on the surface of the liver with a nontarget tissue placed on the back side of the applicator (80 W, 5 min, n = 5). The animals were immediately euthanized after the procedure; the livers were harvested and sectioned perpendicular to the axis of the applicator. In vivo ablation zones were measured following viability staining and assessed on histopathology.ResultsMean ex vivo ablation forward depth was 8.3–15.5 mm. No backward heating was observed at 60 W, 3–5 minutes; directivity was 4.7–11.0 for the other power and time combinations. In vivo ablation forward depth was 10.3–11.5 mm, and directivity was 11.5–16.1. No visible or microscopic thermal damage to nontarget tissues in direct contact with the back side of the applicator was observed.ConclusionsThe side-firing MW ablation applicator can create directional ablation zones in ex vivo and in vivo tissues.  相似文献   
9.
目的 建立稳定的小鼠大脑中动脉远端氯化铁血栓模型,评价其造成的脑损伤及神经功能损伤程 度。 方法 C57BL6/J雄性小鼠随机分为脑缺血组和假手术组。脑缺血组用10%氯化铁(ferric chloride, FeCl3)溶液诱导右侧大脑中动脉远端形成血栓。在术前、术后10 mi n、术后1 d和7 d观测术侧脑血流 和手术动脉血流量的变化。术后1 d观察脑组织梗死率。术后1 d、3 d、5 d、7 d用3种神经学评分[改良 加西亚评分(modified Garcia score,mGS)、改良神经损伤严重程度评分(modified neurological severity scores,mNSS)和15分神经学评估表(15-point neurological evaluation scale,NES)]和胶黏纸测试评价小 鼠神经功能。术后7 d免疫荧光染色标记神经细胞核观察脑组织损伤,标记CD16/32、CD206和Iba1观 察胶质细胞表达。 结果 与假手术组相比,脑缺血组术后10 mi n、1 d、7 d脑表面血流和手术动脉血流下降,术后1 d脑 皮层梗死明显,术后7 d仍有明显脑组织损伤;脑缺血组术后1 d、3 d、5 d和7 d时3种神经学评分及胶 黏纸测试均提示小鼠神经功能不同程度损伤。术后7 d脑缺血组梗死周围皮层M1和M2型胶质细胞表 达增加。 结论 FeCl3溶液可诱导形成稳定的小鼠脑缺血模型,该模型可造成手术侧大脑中动脉远端及脑表 面血流量降低,皮层脑梗死,小鼠神经功能受损,梗死周围胶质细胞表达上调。本研究建立了稳定 氯化铁诱导血栓形成的小鼠脑缺血模型,为脑血栓形成和抗栓药物治疗提供了一种可靠的研究工 具。  相似文献   
10.
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