小儿脓毒血症血清NT-proBNP、CRP、IL-10及TNF-α水平变化及其与预后的关系

［摘要］ 目的分析小儿脓毒血症血清氨基末端脑钠肽前体（N-terminal pro-brain natriuretic peptide,NT-proBNP）、C反应蛋白（C-reactive protein,CRP）、白细胞介素10（interleukin-10,IL-10）及肿瘤坏死因子α（tumor necrosis factor-α,TNF-α）水平变化及其与预后的关系。 方法选取脓毒症患儿80例（观察组）及同期健康体检儿童30例（对照组）,比较2组入院5 d内血清NT-proBNP、CRP、IL-10及TNF-α水平,分析不同病情脓毒症患儿上述指标,依据脓毒症患儿28 d预后情况将其分为预后良好组、预后不良组,对比其入院5 d内平均血清NT-proBNP、CRP、IL-10及TNF-α水平,分析NT-proBNP、CRP、IL-10及TNF-α水平对小儿脓毒症死亡的预测价值。 结果观察组入院第1 天至第5 天血清NT-proBNP、CRP及TNF-α水平呈先升高后降低趋势,而IL-10呈先降低后升高趋势,且观察组第1 d血清NT-proBNP、CRP及TNF-α水平高于对照组,而IL-10水平低于对照组（P＜0.05）;脓毒症休克患儿入院5 d内平均NT-proBNP、CRP及TNF-α高于一般脓毒症、严重脓毒症患儿,而IL-10低于一般脓毒症、严重脓毒症患儿（P＜0.05）;预后良好组入院5 d内平均NT-proBNP、CRP及TNF-α水平低于预后不良组,而IL-10高于预后不良组（P＜0.05）;NT-proBNP预测脓毒症患儿死亡的ROC曲线下面积为0868,大于CRP、IL-10及TNF-α。 结论脓毒症患儿入院5 d内NT-proBNP、CRP、IL-10及TNF-α水平发生明显变化,且与预后有密切关系,应加以监测。     

血管活性肠肽在慢性阻塞性肺病相关肺动脉高压中的研究进展

血管活性肠肽（VIP）是心肺系统最丰富的肽类物质之一,具有强大的抗炎、肺血管与气道舒张作用,以及免疫调节、调节气道分泌等广泛的生物学作用,可减缓COPD相关肺动脉高压（PH）的进展。然而,由于其血浆半衰期较短,给药途径困难,故临床有待进一步研究。本文就现阶段VIP对COPD相关PH治疗的研究进展作一综述。     

Significance of platelet and monocyte activation for therapeutic immunoglobulin-induced thromboembolism

Objectives

Thromboembolic events (TEE) in patients receiving infusions of intravenous immunoglobulin (IVIG) products have recently been associated with contaminating factor XIa. We studied whether platelet and monocyte activation could also be involved.

Methods

Twenty IVIG samples from five manufacturers were tested for the induction of visible whole blood clot formation. A selection of TEE-associated and not associated lots was further analyzed for effects on thromboelastometry, platelet activation and adhesion, as well as monocyte tissue factor surface expression. Pure factor XIa was included for comparison. Western blotting was applied to analyze anti-CD154-reactive proteins in IVIG.

Results

In whole blood, IVIG enhanced macroscopic clotting additively with factor XIa. In monocytes, all IVIG products induced the FcγRII-dependent tissue factor expression to a similar extent, which was not affected by addition of factor XIa. Testing platelet aggregation, IVIG strengthened the ADP and TRAP-6-elicited response. Furthermore, IVIG increased platelet-monocyte adhesion and annexin V binding to platelet microvesicles, and promoted platelet adhesion to IVIG-coated surfaces. The strongest effects were observed with TEE-associated lots. CD154-related proteins were detected in all IVIG products. CD154-related high molecular weight complexes were particularly found in the TEE-associated IVIG. In platelet aggregation, recombinant soluble CD154 enhanced aggregate formation and stability.

Conclusion

Our data demonstrate that IVIG modulate platelet and monocyte activation and can thereby affect the hemostatic balance. These effects are either additive to or independent from factor XIa. CD154-related proteins are assumed to be involved in these interactions, the mechanism of which needs to be elucidated in further studies.     

The role of hypothalamic estrogen receptors in metabolic regulation

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two ‘classical’ estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1^−/−); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism.     

The lowest VE/VCO2 ratio best identifies chronic thromboembolic pulmonary hypertension

Introduction

The natural history of acute pulmonary embolism (PE) under treatment is about a gradual resolution of the thrombi, and uncommonly, the development of chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that ventilatory efficiency parameters during cardiopulmonary exercise testing (CPET) may be able to monitor the process and predict CTEPH.

Methods

15 patients rehabilitated from acute PE (total resolution of thrombi), 44 patients with chronic PE (with residual thrombi), 66 patients with CTEPH, and 36 sedentary healthy controls performed incremental CPET.

Results

The lowest VE/VCO₂ was higher in CTEPH patients than that in chronic PE and rehabilitated patients (43.4 L/min vs 29.9 L/min vs 27.1 L/min, p < 0.005). The VE/VCO₂ slope (48.4 L/min/L/min vs 29.9 L/min/L/min vs 28.0 L/min/L/min, p < 0.005) and oxygen uptake efficiency plateau (OUEP) (37.1 L/min vs 27.0 L/min vs 25.2 L/min, p < 0.005) had the similar changes. In logistic regression analysis, the lowest VE/VCO₂ ≥ 34.35 L/min was the best predictor of CTEPH (OR 159.0, 95% CI 36.0-702.3, p < 0.001). The lowest VE/VCO₂ was higher in chronic PE patients compared with the controls (29.9 L/min vs 26.5 L/min, p < 0.05), but there was no difference between the rehabilitated patients and the controls. In multiple linear regression analysis, the percentage of vascular obstruction by ventilation-perfusion lung scanning (PVO) was the most significant independent predictor for indices of ventilatory efficiency in chronic PE and rehabilitated patients.

Conclusions

CTEPH is associated with weakened ventilatory efficiency. The lowest VE/VCO2 ratio has the best capability to predict CTEPH. Ventilatory inefficiency improves along with recovery of acute PE.     

Sex differences in circadian timing systems: Implications for disease

Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic–pituitary–gonadal axis (HPG), the hypothalamic–adrenal–pituitary (HPA) axis, and sleep–arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions.     

Atrial fibrillation in a tertiary care institute – A prospective study

ObjectiveAtrial fibrillation is the commonest sustained arrhythmia. In western countries the common causes of atrial fibrillation are hypertensive heart disease, dilated cardiomyopathy, and coronary heart disease. Rheumatic heart disease being still common in India, we studied its contribution to atrial fibrillation.Material and methods137 consecutive patients of atrial fibrillation coming to our hospital were subjected to echocardiography to determine the cause.ResultsOut of 137 patients with atrial fibrillation, 76 were female (55.47%) and 61 were male (44.43%). Mean age was 51.24 ± 15.36 years. Commonest cause of AF was rheumatic heart disease found in 84 (61.31%) patients. Next common causes were hypertensive heart disease in 14 (10.2%) patients and chronic obstructive pulmonary disease (COPD) in 14 (10.2%) patients. Mean left atrial size was 47.8 ± 12.25 mm.ConclusionIn our study of patients coming from a rural back ground of North India, more than 60% patients of AF are due to RHD. Hypertensive heart disease and COPD are the next common causes.     

Time dependent history improves QT interval estimation in atrial fibrillation

Purpose

It is not recommended to perform QTc estimation in patients with atrial fibrillation (AF). We evaluated multiple QT interval correction formulas, including a novel time-dependent history approach, in an effort to identify the best method for correcting the QT interval in patients with AF. The ideal correction results in independence between the QTc estimate and HR.

Methods

Per-beat characteristics were derived using SuperECG (Mortara Instrument). Offline beat-to-beat QTc interval estimates were constructed using standard formulae and averaged (2–10) groups constructed.

Results

Seventy-one patients were included, age 67±10 years, 69% men. Mean-mean QTc intervals varied by correction (range 394–459 ms). Averaging resulted in the same mean-mean QTc estimate, but significantly reduced variability by up to 55%. Time-dependent RR interval history reduced variability the most (Δ80%), increased QT/RR dynamics (m=.03 vs .17), and was independent with HR (m = 0.0008).

Conclusions

Our data suggests that QTc interval estimation in patients with AF can be performed reliably using time-dependent history (RRc) outperforming other correction methods.     

Targeting protein-trafficking pathways alters melanoma treatment sensitivity

Protein-trafficking pathways are targeted here in human melanoma cells using methods independent of oncogene mutational status, and the ability to up-regulate and down-regulate tumor treatment sensitivity is demonstrated. Sensitivity of melanoma cells to cis-diaminedichloroplatinum II (cDDP, cis-platin), carboplatin, dacarbazine, or temozolomide together with velaparib, an inhibitor of poly (ADP ribose) polymerase 1, is increased by up to 10-fold by targeting genes that regulate both protein trafficking and the formation of melanosomes, intracellular organelles unique to melanocytes and melanoma cells. Melanoma cells depleted of either of the protein-trafficking regulators vacuolar protein sorting 33A protein (VPS33A) or cappuccino protein (CNO) have increased nuclear localization of cDDP, increased nuclear DNA damage by platination, and increased apoptosis, resulting in increased treatment sensitivity. Depleted cells also exhibit a decreased proportion of intracellular, mature melanosomes compared with undepleted cells. Modulation of protein trafficking via cell-surface signaling by binding the melanocortin 1 receptor with the antagonist agouti-signaling protein decreased the proportion of mature melanosomes formed and increased cDDP sensitivity, whereas receptor binding with the agonist melanocyte-stimulating hormone resulted in an increased proportion of mature melanosomes formed and in decreased sensitivity (i.e., increased resistance) to cDDP. Mutation of the protein-trafficking gene Hps6, known to impair the formation of mature melanosomes, also increased cDDP sensitivity. Together, these results indicate that targeting protein-trafficking molecules markedly increases melanoma treatment sensitivity and influences the degree of melanosomes available for sequestration of therapeutic agents.