Evaluation of Toll-like,chemokine, and integrin receptors on monocytes and neutrophils from peripheral blood of septic patients and their correlation with clinical outcomes

Recognition of pathogens is performed by specific receptors in cells of the innate immune system, which may undergo modulation during the continuum of clinical manifestations of sepsis. Monocytes and neutrophils play a key role in host defense by sensing and destroying microorganisms. This study aimed to evaluate the expression of CD14 receptors on monocytes; CD66b and CXCR2 receptors on neutrophils; and TLR2, TLR4, TLR5, TLR9, and CD11b receptors on both cell types of septic patients. Seventy-seven septic patients (SP) and 40 healthy volunteers (HV) were included in the study, and blood samples were collected on day zero (D0) and after 7 days of therapy (D7). Evaluation of the cellular receptors was carried out by flow cytometry. Expression of CD14 on monocytes and of CD11b and CXCR2 on neutrophils from SP was lower than that from HV. Conversely, expression of TLR5 on monocytes and neutrophils was higher in SP compared with HV. Expression of TLR2 on the surface of neutrophils and that of TLR5 on monocytes and neutrophils of SP was lower at D7 than at D0. In addition, SP who survived showed reduced expression of TLR2 and TLR4 on the surface of neutrophils at D7 compared to D0. Expression of CXCR2 for surviving patients was higher at follow-up compared to baseline. We conclude that expression of recognition and cell signaling receptors is differentially regulated between SP and HV depending on the receptor being evaluated.     

Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13^BN rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure.     

Effects of Polysaccharides from Gynostemma Pentaphyllum (Thunb.), Makino on Physical Fatigue

Background

Gynostemma pentaphyllum (Thunb.) Makino has been reported to have a wide range of health benefits in Chinese herbal medicines. Polysaccharides from Gynostemma pentaphyllum (PGP), has been identified as one of the active ingredients responsible for its biological activities. Although many pharmacological activities of PGP have received a great deal of attention, there is limited evidence for the anti-fatigue effects of PGP. The purpose of this study was to investigate the effects of polysaccharides from PGP on physical fatigue.

Materials and method

The rats were divided into four groups, with 10 animals per group: control (C), group, low-treated (LT), group, medium-treated (MT), group, and high-treated (HT), group. The C group received distilled water, while LT, MT and HT groups were given various doses of PGP (100, 200, 400 mg/kg· d). After 30 days, forced swimming test was carried out in an acrylic plastic pool, then the exhaustive swimming time of rats and some biochemical parameters related to fatigue were measured. The data obtained showed that PGP could extend the exhaustive swimming time of the rats, as well as decrease the blood lactic acid (BLA), and blood urea nitrogen (BUN), concentrations, and increase the hemoglobin, liver glycogen and muscle glycogen concentrations.

Result

The data obtained showed that different doses of PGP could extend the exhaustive swimming time of the rats, as well as decrease the BLA and BUN concentrations, and increase the hemoglobin, liver glycogen and muscle glycogen concentrations, which suggests that PGP had significant anti-fatigue effects on rats.

Conclusion

PGP may be of use as a potential anti-fatigue agent, but there is a need for further research on long-term use in order to show its positive effects on physical fatigue.     

Biphasic intra-thoracic pressure regulation augments cardiac index during porcine peritonitis: a feasibility study

Preservation of cardiac output (CO) and pulmonary artery pressure (PAP) is vital to maintaining tissue oxygenation in sepsis. This feasibility study tested the hypothesis that therapeutic intra-thoracic pressure regulation (tIPR), delivered with a novel device, was designed to non-invasively enhance venous return by creating sub-atmospheric intra-thoracic pressure during the expiratory phase of mechanical ventilation, improves CO without fluid resuscitation in a porcine E. coli peritonitis model of sepsis. Seven pigs were intubated, anaesthetized and instrumented with a Swan-Ganz and femoral artery catheter. After a 30?min basal period, a fibrin clot containing 4–5?×?10⁹ cfu kg^?1 E. coli O111.B4 was implanted in the peritoneum. One hour after clot implantation, tIPR was utilized for 30?min and then removed from the ventilator circuit for 30?min. This tIPR cycle was repeated 4-times. Changes in haemodynamic parameters were calculated by comparing pre-tIPR values to peak values during tIPR administration. Following peritonitis, tIPR significantly increased the peak cardiac index (mean?±?SEM) (14.8?±?2.6 vs 7.9?±?2.3?ml kg^?1) and mean arterial pressure (10.2?±?1.5 vs 4.9?±?1.1?mmHg) and simultaneously decreased PAP (?7.7?±?1.5 vs ?2.7?±?0.8?mmHg). These results support the feasibility of the concept that therapeutic application of negative expiratory pressure may provide a non-invasive and complementary approach to increase cardiac output and organ perfusion in the setting of septic shock.     

多巴胺受体2减轻离体大鼠心肌缺血/再灌注损伤

目的 观察多巴胺受体2(DR2)对离体大鼠心肌缺血/再灌注(I/R)损伤的影响及其可能机制.方法 将大鼠40只,每组n=10,随机分成对照组(control)、I/R组、10 pmol/L Bromocriptine(DR2激动剂)组(Bro),10 μmol/L Haloper-idol(DR2抑制剂)组(Hal).用Langendorff离体灌流装置,复制大鼠心肌I/R损伤模型.Powerlab生理记录仪记录心功能;比色法测定冠脉流出液LDH、CK活性和心肌组织匀浆SOD活性以及MDA含量;TUNEL染色检测心肌细胞凋亡;Western blot检测DR2、Bcl-2、caspase-3和caspase-9蛋白的表达.结果 与对照组比较,I/R组DR2、Bcl-2、caspase-3和cmpase-9蛋白表达、LDH和CK活性、MDA含量和细胞凋亡率均增加(P＜0.01),唯有SOD活性降低,心功能减弱(P＜0.01).与I/R组比较,Bro降低LDH和CK活性、MDA含量、细胞凋亡率、caspase-3和caspase-9的表达,升高SOD活性,改善心功能和进一步增加Bcl-2的表达(P ＜0.01);Hal对上述指标影响不显著.结论 DR2可减轻心肌I/R损伤,其机制与抗氧化、清除自由基、上调Bcl-2表达以及下调caspase-3和caspase-9的表达有关.     

Urinary 1H-NMR and GC-MS metabolomics predicts early and late onset neonatal sepsis

The purpose of this article is to study one of the most significant causes of neonatal morbidity and mortality: neonatal sepsis. This pathology is due to a bacterial or fungal infection acquired during the perinatal period. Neonatal sepsis has been categorized into two groups: early onset if it occurs within 3–6 days and late onset after 4–7 days. Due to the not-specific clinical signs, along with the inaccuracy of available biomarkers, the diagnosis is still a major challenge. In this regard, the use of a combined approach based on both nuclear magnetic resonance (¹H-NMR) and gas-chromatography-mass spectrometry (GC-MS) techniques, coupled with a multivariate statistical analysis, may help to uncover features of the disease that are still hidden. The objective of our study was to evaluate the capability of the metabolomics approach to identify a potential metabolic profile related to the neonatal septic condition. The study population included 25 neonates (15 males and 10 females): 9 (6 males and 3 females) patients had a diagnosis of sepsis and 16 were healthy controls (9 males and 7 females). This study showed a unique metabolic profile of the patients affected by sepsis compared to non-affected ones with a statistically significant difference between the two groups (p = 0.05).     

小儿脓毒症CD62p、CD63及CD64分子变化及临床意义探讨

目的探讨脓毒症患儿血小板仅颗粒膜糖蛋白（CD62p）、溶酶体膜蛋白（CD63）及中性粒细胞表面膜糖蛋白（CD64）的变化及意义。方法2010年3月至2013年3月哈尔滨市儿童医院感染内科收治的脓毒症患儿56例,其中严重脓毒症16例,一般脓毒症40例,另设健康对照组34例。应用流式细胞术检测儿童外周血的血小板表面活性标记糖蛋白CD62p、CD63及中性粒细胞CD64表达,并进行比较。结果严重脓毒症组患儿外周血的CD62p、CD63及CD64水平明显高于一般脓毒症组,差异有统计学意义（P〈0．01）;一般脓毒症组患儿CD62p、CD63及CD64水平明显高于健康对照组,差异有统计学意义（P〈0．01）。相关性分析显示,脓毒症患儿的CD62p、CD63与CD64水平呈正相关（r=0．817、0．796,P均〈0．001）,CD62p、CD63、CD64水平与小儿危重病例评分呈正相关（CD62p：r=0．883,P〈0．001;CD63：r=0．862,P〈0．001;CD64：r=0．805,P〈0．001）。结论CD62p、CD63、CD64与感染和炎症严重程度密切相关,可作为评价疾病严重程度及预后的指标。     

危重症患儿血清上皮来源中性粒细胞活化肽-78的变化及意义

目的 探讨危重症患儿血清上皮来源中性粒细胞活化肽-78(ENA-78)的变化,及其与儿童危重症病情严重程度和预后的关系.方法 采用前瞻性病例对照研究,选取2013年9月至11月上海交通大学附属儿童医院重症医学科收治的42例危重症患儿(危重症组),入院后24h内(急性期)和第7天(恢复期)留取血标本;选取本院同期42例儿童体检残血样本作为对照.采用儿童危重病例评分标准(PCIS)和儿童死亡危险因素评分(PRISMⅢ)评估病情的危重程度;双抗体夹心酶联免疫法测定血清中ENA-78水平.结果 1.对照组血液ENA-78水平为(0.44 ±0.28) ng/L;危重症组急性期ENA-78为(2.85±0.89) ng/L,恢复期为(1.00±0.64) ng/L,危重症组与对照组、急性期与恢复期ENA-78水平比较差异均有统计学意义(P均=0.000).2.ENA-78水平与PCIS评分呈负相关(r=-0.724,P=0.000);PRISMⅢ≥10分组血清ENA-78水平明显高于PRISMⅢ＜10分组(P =0.000).危重症患儿中,存活组ENA-78水平与死亡组比较差异有统计学意义(P=0.000).3.严重感染患儿血清ENA-78水平与非感染性疾病组比较差异有统计学意义(P =0.000).4.随着器官功能障碍损伤范围扩大ENA-78水平相应上升,差异有统计学意义(P =0.000).结论 危重症患儿存在血液ENA-78水平的变化,测定血液中ENA-78水平,能对评估疾病严重程度及判断预后提供参考.