Pain management of nalbuphine and sufentanil in patients admitted intensive care unit of different ages.

BACKGROUND: Pain relief for patients in the intensive care unit (ICU) can improve treatment outcomes and reduce the burden on doctors and nurses. This study aims to report the clinical analgesic and sedative effects of nalbuphine and sufentanil on ICU patients. METHODS: This study retrospectively analyzed the medical records of 87 critically ill patients who received nalbuphine or sufentanil infusion in the ICU, including demographic data, diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II, Critical Care Pain Observation Tool (CPOT), Richmond Agitation-Sedation Scale (RASS), systolic and diastolic blood pressure, heart rate and blood oxygen saturation (SpO2). The primary outcomes of this study were CPOT and RASS scores. The secondary outcomes were hemodynamic changes, including systolic blood pressure, diastolic blood pressure, heart rate, and SpO2. The adverse events recorded during pain management, such as hypoxemia, respiration depression and bradycardia, were also collected and analyzed. RESULTS: None of the patients in both groups experienced episode of hypoxemia, respiration depression and bradycardia. However, age-stratified analyses showed that nalbuphine has a better analgesic effect than sufentanil for patients aged ≤ 60 (P < 0.05). In contrast, sufentanil showed a better analgesic effect than nalbuphine for patients aged > 60 ( P < 0.05). Furthermore, nalbuphine has a significantly better sedative effect than sufentanil for patients aged ≤ 60 (P < 0.05). CONCLUSION: ICU patients of different age groups may be suitable for different analgesics. For patients under the age of 60, nalbuphine has better analgesia and sedation than sufentanil, and does not cause respiratory depression and drastic hemodynamic changes.

NFAT Overexpression Correlates with CA72-4 and Poor Prognosis of Ovarian Clear-Cell Carcinoma Subtype.

Current biomarkers did not overcome the limitations of clinical application due to the heterogeneity of ovarian tumors. The role of nuclear factor of activated T cells (NFAT) in the prognosis of different histological subtypes of ovarian cancer remains unclear. NFAT expression was analyzed in 302 ovarian tumors from The Cancer Genome Atlas (TCGA) dataset and was further confirmed by 88 ovarian tumor specimens, including 30 clear-cell carcinoma, 34 serous carcinoma, and 24 papillary serous cystadenocarcinoma. The correlations between NFAT expression, cancer biomarkers, and clinical characteristics in different subtypes of ovarian tumors were analyzed. ALGGEN PROMO, reporter assay, and NFAT overexpression and knockdown were used to identify chondroadherin (CHAD) as the downstream target of NFAT. NFAT was significantly upregulated only in late-stage clear-cell carcinoma, but not in other two subtypes. NFAT levels were correlated with CA72-4 levels and poor overall survival and disease-free survival (P < 0.05), suggesting that NFAT together with CA72-4 were specific prognostic markers for clear-cell carcinoma. Pathological stage and lymph node metastasis were the prognostic factors affecting serous carcinoma (P < 0.05), while CA-125 was the prognostic factor affecting papillary serous cystadenocarcinoma (P < 0.05). PROMO and reporter assay indicated that CHAD was the downstream target of NFAT. In addition, NFAT overexpression and silencing increased and reduced CHAD expression, respectively. NFAT together with CA72-4 were specific tumor markers for risk assessment of unique clear-cell subtype of ovarian tumors. CHAD was identified as the downstream target gene of NAFT and was associated with poor survival of ovarian cancer.

Higher expression of calcineurin predicts poor prognosis in unique subtype of ovarian cancer.

BACKGROUND: The role of calcineurin/NFAT signaling in ovarian cancer has been unknown. NFAT was significantly overexpressed in ovarian cancer tissues and that overexpression of NFAT was significantly associated with metastasis and poor prognosis on clinical tissue level. To investigate whether NFAT upstream protein, calcineurin (CN), affects the prognosis in various histological subtype of ovarian cancer (OC). METHODS: The association between CN and clinical features was analyzed in 50 OC patients treated from 2007 to 2012. CN expression was examined using immunohistochemistry. We observed the association of CN expression with the prognosis in these patients. RESULTS: CN expression was significantly increased in later-stage tumor tissue of serous carcinoma compared with those with early-stage. The expression of CN positively correlated with the serum cancer antigen 125 (CA125) level in ovarian clear-cell carcinoma and the serum alpha-fetoprotein (AFP) level in papillary serous cystadenocarcinoma. Particularly, higher CN expression in tumor tissues significantly correlated with reduced overall survival among patients with serous carcinoma. In addition, the serum cancer antigen 72-4 (CA72-4) level, serum carcinoembryonic antigen (CEA) levels, pathological stage, lymph node metastasis, and chemotherapeutic resistance were identified as significant prognostic factors in ovarian clear-cell carcinoma, serous carcinoma, or papillary serous cystadenocarcinoma. CONCLUSIONS: CN is upregulated in ovarian cancer tissues with later-stage and that the expression of CN, CA72-4, and CEA was remarkably associated with poor prognosis in unique subtype of ovarian cancer. CN levels may be investigated for use as a prognostic biomarker for risk assessment in unique subtype of OC patients.

Autophagy Enhancing Contributes to the Organ Protective Effect of Alpha-Lipoic Acid in Septic Rats.

Alpha-lipoic acid (ALA) reportedly has protective effects against sepsis, which is a leading cause of mortality worldwide and is associated with multiple organ dysfunction. The present study aimed to investigate further the possible action mechanisms of ALA. Male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP) in order to establish a sepsis model. The rats received an oral gavage of 200 mg/kg ALA or saline immediately after surgery. The heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and maximum rising and lowering rates of left ventricular pressure (±dp/dt) were examined for assessing the cardiac function. Blood urea nitrogen (BUN) and serum creatinine levels were assessed for evaluating renal function. Neutrophil gelatinase-associated lipocalin (NAGL) was examined for reflecting acute renal injury. Histopathological alterations of the small intestine were examined by hematoxylin-eosin staining. The ultrastructure of the small intestine and kidney was observed under electron microscopy. The levels of autophagy- and inflammation-associated proteins were determined via western blot analysis. The binding of nuclear factor-kappa B (NF-κB) to DNA was tested via an electrophoretic mobility shift assay. Cell apoptosis was examined using TUNEL staining. ALA treatment improved the survival rate, restored the loss of body weight and pro-inflammatory cytokines production in the serum of CLP-induced septic rats. ALA improved the cardiac and renal functions, downregulated the expression levels of interleukin-1ß, tumor necrosis factor-α, and inducible nitric oxide synthase in the myocardium and small intestine of septic rats. ALA treatment also inactivated the NF-κB signaling pathway in the small intestine. An examination of autophagy showed that ALA increased the LC3II/I ratio, upregulated Atg5, Atg7, and beclin-1 and downregulated p62 protein levels in the myocardium, kidney, and small intestine of septic rats, and further promoted autophagosome accumulation in the kidney and small intestine. In addition, ALA could also reduce cell apoptosis in myocardium, kidney and small intestine tissues. These effects can be completely or party inhibited by 3-MA. Our findings suggest that autophagy enhancing may contribute to the organ protective effect of ALA in septic rats.

microRNA-542-5p protects against acute lung injury in mice with severe acute pancreatitis by suppressing the mitogen-activated protein kinase signaling pathway through the negative regulation of P21-activated kinase 1.

Severe acute pancreatitis (SAP) is a condition associated with high rates of mortality and lengthy hospital stays. In the current study, SAP mouse models were established in BALB/c wild-type and P21-activated kinase 1 (PAK1) knockdown mice with the objective of determining the expression of microRNA-542-5p (miR-542-5p) and the subsequent elucidation of the mechanism by which it influences acute lung injury (ALI) by mediating mitogen-activated protein kinase (MAPK) signaling and binding to PAK1. The targeting relationship between miR-542-5p and PAK1 was verified using the bioinformatics prediction website and by the means of a dual-luciferase reporter assay. Following the SAP model establishment, the mice were assigned into various groups with the introduction of different mimic and inhibitors in an attempt to investigate the effects involved with miR-542-5p on inflammatory reactions among mice with SAP-associated ALI. Our results indicated that PAK1 was targeted and negatively mediated by miR-542-5p. Mice with SAP-associated ALI exhibited an increased wet-to-dry weight ratio, myeloperoxidase activity, serum amylase activity, TNF-α, interleukin-1 beta (IL-1ß), and intercellular adhesion molecule-1 (ICAM-1) contents, p-p38MAPK, p-ERK1/2, and p-JNK protein levels as well as PAK1 positive expression, while decreased miR-542-5p levels were observed. Functionally, overexpression of miR-542-5p improves ALI in mice with SAP via inhibition of the MAPK signaling pathway by binding to PAK1.Based on the evidence from experimental models, miR-542-5p was shown to improve ALI among mice with SAP, while suggesting that the effect may be related to the inactivation of the MAPK signaling pathway and downregulation of PAK1 gene. Thus, miR-542-5p could serve as a promising target for ALI treatment.

MIP-1α induces inflammatory responses by upregulating chemokine receptor 1/chemokine receptor 5 and activating c-Jun N-terminal kinase and mitogen-activated protein kinase signaling pathways in acute pancreatitis.

OBJECTIVE: We aimed to investigate the association of macrophage inflammatory protein (MIP)-1α (CCL3) expression with the severity of acute pancreatitis (AP). METHODS: The patients with AP were selected and divided into mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP) groups according to the severity of AP. The pancreatic acinar cell line Ar42 j was treated with cerulein to induce in vitro cell AP model. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the activation of the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) signaling pathway in stimulated or transfected Ar42 j cells were detected. RESULTS: We detected that the upregulation of MIP-1α was associated with the severity of AP. Patients with SAP showed the highest MIP-1α contents, followed by MSAP, and, lastly, MAP. In cerulein-stimulated Ar42 j cells, the upregulation of MIP-1α, CCR5, TNF-α, and IL-6 was time dependent. In addition, in human recombinant MIP-1α treated Ar42 j cells, the upregulation of TNF-α and IL-6 was MIP-1α-dose-dependent. In contrast, we detected the inhibition of TNF-α and IL-6 in MIP-1α small interfering RNA (siRNA)-treated cells. Also, the activation of the JNK/p38 MAPK signaling pathway was induced and inhibited by human recombinant MIP-1α and MIP-1α siRNA, respectively. CONCLUSION: These results suggested that MIP-1α might be used as a biomarker for the prognosis of AP severity. The MIP-1α-induced inflammatory responses in AP were mediated by TNF-α and IL-6, which were associated with the activation of the JNK/p38 MAPK signaling pathway.

MicroRNA-339-3p alleviates inflammation and edema and suppresses pulmonary microvascular endothelial cell apoptosis in mice with severe acute pancreatitis-associated acute lung injury by regulating Anxa3 via the Akt/mTOR signaling pathway.

Severe acute pancreatitis (SAP) is a disease with a high mortality. Patients with SAP may also be complicated with acute lung injury (ALI). So far the therapy for SAP-ALI is still limited. Emerging evidences demonstrate that microRNAs (miRs) could play a role in SAP-ALI. This study aims to define the role of miR-339-3p in SAP-ALI via Anxa3 through the Akt/mTOR signaling pathway. Ten mice were selected as sham group and 36 mice as model group which further assigned into different groups. Relationship between miR-339-3p and Anxa3 was detected by dual luciferase reporter gene assay. Levels of TNF-α, IL-6, and serum amylase (AMS) and myeloperoxidase (MPO) in lung tissues were determined by ELISA. Expression of related genes in pulmonary vascular endothelial cells (PMVECs) and lungs tissues was determined by Western blot analysis and RT-qPCR. Cell apoptosis was detected by flow cytometry and TUNEL. SAP-ALI mice had decreased survival rate, increased levels of TNF-α, IL-6, AMS, MPO, and Schmidt scores. miR-339-3p was poorly expressed in lung tissue of SAP-ALI mice while Anxa3 was reciprocal. Anxa3 was targeted by miR-339-3p. miR-339-3p inhibited the relative expression of the Akt/mTOR signaling pathway-related proteins, alleviated inflammation and edema of SAP-ALI mice, and suppressed apoptosis of PMVECs; Anxa3 exhibited opposite trends. In conclusion, overexpressed miR-339-3p could suppress Anxa3 to inhibit the Akt/mTOR signaling pathway, so as to decrease tissue edema, inflammation, and PMVEC apoptosis in SAP-ALI mice.

[Effect of vitamin D3 on the severity and prognosis of patients with sepsis: a prospective randomized double-blind placebo study].

OBJECTIVE: To observe the relationship between vitamin D3 and the severity as well as prognosis in patients with sepsis, and to explore whether exogenous vitamin D3 can improve the prognosis in patients with sepsis. METHODS: A prospective randomized double-blind placebo study was conducted. Fifty-seven patients with sepsis admitted to intensive care unit (ICU) of Shengjing Hospital Affiliated to China Medical University from March to November in 2015 were enrolled. Twenty patients with systemic inflammatory response syndrome (SIRS) and 20 healthy volunteers with normal physical examination as control were enrolled during the same time. Patients with sepsis were divided into general sepsis group and severe sepsis group (including septic shock) according to the criteria for the diagnosis of severe sepsis and septic shock in 2012. According to the diagnostic criteria established by the American Endocrine Society, and on the basis of 25-hydroxy vitamin D3 [25(OH)D3], the sepsis patients with deficiency [25(OH)D3 20-30 µg/L] or insufficiency [25(OH)D3 < 20 µg/L] of vitamin D were divided into D3 treatment group (supplemented 300 kU vitamin D3) and placebo group (injected 1 mL physiological saline). 28th day was set as the end point, and the patients with sepsis were divided into survival group and death group. The levels of serum 25(OH)D3 in each group were measured by electrochemical luminescence method, and the difference in 25(OH)D3 levels among patients with different severity, gender, and age were recorded. Procalcitonin (PCT), C-reactive protein (CRP), blood routine, liver and kidney function, electrolytes and arterial blood gas analysis, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure score (SOFA), duration of mechanical ventilation, and length of ICU stay of patients with sepsis were observed. Multivariate Cox proportional hazard regression analysis was used to analyze the risk factors of prognosis in patients with sepsis. RESULTS: (1) In 57 patients with sepsis, there were 15 patients in general sepsis group, and 42 in severe sepsis group; 29 in D3 treatment group, and 28 in the placebo group; 8 patients died within 28 days with mortality rate of 14.04%. (2) The levels of serum 25(OH)D3 in sepsis group and SIRS group were significantly lower than those in healthy control group [µg/L: 3.92 (< 3.00, 11.22), 6.99 (3.51, 9.77) vs. 17.25 (13.48, 22.50), both P < 0.01], but there was no significant difference in the serum 25(OH)D3 level between sepsis group and SIRS group as well as patients with different degrees of sepsis. The serum 25(OH)D3 level in female patients with sepsis (n = 24) was significantly lower than that in male (n = 33), and the difference was statistically significant [µg/L: <3.00 (<3.00, 3.87) vs. 11.96 (5.14, 17.29), Z = -4.020, P = 0.000]. There was no significant difference in serum 25(OH)D3 level between the young (age <60 years old, n = 30) and the old (age ≥ 60 years old, n = 27) patients with sepsis [µg/L: 4.54 (<3.00, 9.88) vs. 3.00 (<3.00, 15.08), Z = -0.601, P = 0.548]. (3) In patients with sepsis, there was no significant difference in the duration of mechanical ventilation [hours: 41.00 (7.50, 82.50) vs. 67.00 (4.75, 127.75)], length of ICU stay (days: 5.48±4.08 vs. 6.68±4.87) and 28-day mortality (10.34% vs. 17.86%) between D3 treatment group and placebo group (all P > 0.05). It was shown by Kaplan-Meier survival curve analysis that there was no significance in 28-day accumulated survived rate between the two groups [log-rank test: χ 2 = 0.222, P = 0.638]. It was shown by multivariate Cox regression analysis that APACHE II score [relative risk (RR) = 8.487, 95% confidence interval (95%CI) = 1.506-47.835, P = 0.015] and 25(OH)D3 < 20 µg/L (RR = 0.088, 95%CI = 0.013-0.592, P = 0.012) were the risk factors of prognosis in patients with sepsis. CONCLUSIONS: The serum 25(OH)D3 level in ICU patients with sepsis was lower than that in healthy people, but there was no significant difference between patients with sepsis and SIRS. The serum 25(OH)D3 level in sepsis patients was related with gender, and the level of the female was lower than that of the male, but was not related with age. Exogenous vitamin D3 supplementation cannot improve the prognosis of ICU patients with sepsis. APACHE II score and 25(OH)D3 < 20 µg/L were risk factors for the prognosis in ICU patients with sepsis.

The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats.

Sepsis-induced acute kidney injury (AKI) represents a major cause of mortality in intensive care units. Sivelestat, a selective inhibitor of neutrophil elastase (NE), can attenuate sepsis-related acute lung injury. However, whether sivelestat can preserve kidney function during sepsis remains unclear. In this study, we thus examined the effects of sivelestat on sepsis-related AKI. Cecal ligation and puncture (CLP) was performed to induce multiple bacterial infection in male Sprague-Dawley rats, and subsequently, 50 or 100 mg/kg sivelestat were administered by intraperitoneal injection immediately after the surgical procedure. In the untreated rats with sepsis, the mean arterial pressure (MAP) and glomerular filtration rate (GFR) were decreased, whereas serum blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) levels were increased. We found that sivelestat promoted the survival of the rats with sepsis, restored the impairment of MAP and GFR, and inhibited the increased BUN and NGAL levels; specifically, the higher dose was more effective. In addition, sivelestat suppressed the CLP-induced macrophage infiltration, the overproduction of pro-inflammatory mediators (tumor necrosis factor­α, interleukin-1ß, high-mobility group box 1 and inducible nitric oxide synthase) and serine/threonine kinase (Akt) pathway activation in the rats. Collectively, our data suggest that the inhibition of NE activity with the inhibitor, sivelestat, is beneficial in ameliorating sepsis-related kidney injury.

Rosiglitazone attenuates renal injury caused by hyperlipidemic pancreatitis.

Hyperlipidemic pancreatitis (HP) is a serious inflammatory disease with very high mortality and multiple organ injuries including renal injury. Rosiglitazone (Ros), an agonist of peroxisome proliferator activated receptor-γ (PPAR-γ), was reported to show a protective role against pancreatitis. However, whether Ros has an effect on renal injury caused by HP is not yet clear. In the present study, the function of Ros was explored using ELISA, RT-PCR, western blot, PAS staining and immunohistochemistry. Results of this study showed that Ros could inhibit the activation of NF-κB and MAPK P38 signaling pathways, relieve inflammatory response and inhibit cell apoptosis, thus attenuating renal injury caused by HP. This study suggested that Ros might be a promising drug for the treatment of renal injury caused by HP and also laid theoretical foundation for the development of renal injury treatment.

When to initialize enteral nutrition in patients with severe acute pancreatitis? A retrospective review in a single institution experience (2003-2013).

OBJECTIVE: The present retrospective study aimed to analyze the optimal time to initiate enteral nutrition (EN) in patients with severe acute pancreatitis at a single Chinese institution (China Medical University Hospital). METHODS: A total of 1196 patients with severe acute pancreatitis were admitted in the intensive care unit between November 2003 and June 2013; 1092 patients were selected and were divided into the early and delayed EN groups, according to their initial timing of EN. RESULTS: Five hundred sixty-six patients were administered with the delayed EN, and 526 with the early EN. Both groups had similar severity of pancreatic necrosis, but organ failure developed in 81% patients of the delayed EN group and 21% in the early EN group (P < 0.01). The numbers of septic necrosis and morbidity were significantly higher in the delayed EN group than in the early EN (P < 0.01). CONCLUSIONS: The early EN had significant benefits over the delayed EN in the decrease of organ failure and mortality; our findings suggested that the first 48 hours of administration in the intensive care unit was the optimal time to start EN.

Alpha-lipoic acid exerts anti-inflammatory effects on lipopolysaccharide-stimulated rat mesangial cells via inhibition of nuclear factor kappa B (NF-κB) signaling pathway.

Sepsis is often initiated by invasive infection, characterized by overwhelming induction of pro-inflammatory cytokines. The incidence and mortality of sepsis and the associated development of acute kidney injury (AKI) remain high, and lines of research into potential treatments are needed. This study was conducted to investigate effects of alpha-lipoic acid (ALA) on septic AKI in vitro. ALA of 200 or 400 µM was used to pretreat rat HBZY-1 mesangial cells before commencement of 1 µg/mL lipopolysaccharide (LPS). Our data indicated that ALA pretreatment reduced LPS-stimulated release of inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1 beta (IL-1ß), as well as IL-6, in HBZY-1 cell supernatant. Moreover, LPS-induced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was inhibited by ALA pretreatment, and consequently, the secretion levels of their respective enzymatic products prostaglandin E2 (PGE2) and nitric oxide (NO) were significantly decreased. LPS-enhanced phosphorylation of nuclear factor kappa B (NF-κB) inhibitor alpha (IκBα) and IκB kinase alpha/beta (IKKα/ß) and nuclear translocation of NF-κB subunit p65 in HBZY-1 cells were inhibited by ALA pretreatment. Additionally, the NF-κB inhibitor N-acetylcysteine (NAC) exerted similar inhibitory effects as ALA on COX-2 and iNOS expression. In summary, our study demonstrates that ALA mitigates LPS-induced inflammatory responses in rat mesangial cells probably via inhibition of NF-κB signaling pathway, suggesting a therapeutic potential of ALA in AKI related to sepsis.

[The effects of preconditioning and postconditioning with isoflurane on focal cerebral ischemi/reperfusion injury in rats].

OBJECTIVE: To investigate the effects of preconditioning and postconditioning with isoflurane on pro-inflammatory cytokines and lipid peroxidation in focal cerebral ischemic/reperfusion (I/R) injury in rats. METHODS: Thirty-two Sprague-Dawley (SD) rats were randomly divided into four groups: control group, model group, isoflurane preconditioning group and isoflurane postconditioning group, with 8 rats in each group. Rats in control group did not receive any challenge. In rats of model group right middle cerebral artery occlusion (MCAO) was conducted for 90 minutes. Rats in isoflurane preconditioning group received 2% isoflurane exposure for 30 minutes 24 hours before MCAO for 90 minutes. Rats in isoflurane postconditioning group were given 60-minute 2% isoflurane exposure after reperfusion of right MCAO. Twenty-four hours after the procedure, all rats were anesthetized with isoflurane, and blood sample taken from the heart was centrifuged, and the pro-inflammatory cytokines, including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), and lipid peroxidation products such as malonaldehyde (MDA) and superoxide dismutase (SOD) were determined. The mRNA and protein expression levels of matrix metalloproteinase (MMP-2, MMP-9), tight junction protein Calaudin-5 and Occludin were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot. RESULTS: Compared with control group, serum levels of IL-1ß, TNF-α and MDA were elevated and activity of SOD decreased in rats of model group (IL-1ß: 76.81±11.14 ng/L vs. 52.43 ± 8.86 ng/L, TNF-α: 64.93 ± 10.81 ng/L vs. 33.64 ± 7.94 ng/L, MDA: 8.63 ± 1.42 µmol/L vs. 4.14 ± 0.98 µmol/L, SOD: 0.95 ± 0.21 U/L vs. 2.36 ± 0.80 U/L, all P<0.05). After isoflurane preconditioning and postconditioning, compared with model group, the levels of IL-1ß, TNF-α and MDA were lowered, while activity of SOD was increased (IL-1ß: 54.37 ± 9.06 ng/L, 56.82 ± 8.67 ng/L vs. 76.81 ± 11.14 ng/L, TNF-α: 43.72 ± 6.16 ng/L, 39.49 ± 9.34 ng/L vs. 64.93 ± 10.81 ng/L, MDA: 5.65 ± 0.83 µmol/L, 5.82 ± 0.78 µmol/L vs. 8.63 ± 1.42 µmol/L, SOD: 1.64 ± 0.47 U/L, 1.71 ± 0.52 U/L vs. 0.95 ± 0.21 U/L, all P<0.05). Focal cerebral I/R injury could lead to an increased expression of MMP accompanied with a decreased expression of tight junction protein. Compared with model group, after isoflurane preconditioning and postconditioning, it was found that there were decreased mRNA and protein expression of MMP-2 and MMP-9 (MMP-2 mRNA: 1.25 ± 0.08, 1.32 ± 0.12 vs. 2.48 ± 0.26, MMP-2 protein: 1.56 ± 0.09, 1.50 ± 0.08 vs. 2.12 ± 0.11; MMP-9 mRNA: 1.26 ± 0.13, 1.20 ± 0.12 vs. 2.74 ± 0.28, MMP-9 protein: 1.53 ± 0.04, 1.51 ± 0.05 vs. 2.23 ± 0.09, all P<0.05) and increased levels of Calaudin-5 and Occludin (Claudin-5 mRNA: 0.40 ± 0.08, 0.38 ± 0.06 vs. 0.28 ± 0.03, Claudin-5 protein: 0.80 ± 0.06, 0.81 ± 0.07 vs. 0.39 ± 0.02; Occludin mRNA: 0.54 ± 0.07, 0.50 ± 0.08 vs. 0.26 ± 0.06, Occludin protein: 0.64 ± 0.06, 0.69 ± 0.05 vs. 0.49 ± 0.02, all P<0.05). CONCLUSIONS: Preconditioning and postconditioning with isoflurane can lower the levels of pro-inflammatory cytokines and the degree of lipid peroxidation, and lower the hydrolytic activity of MMP to the tight junction protein in cerebral tissue, thereby decrease the loss of tight junction protein and alleviate I/R injury.

Integrin alphavbeta6 is involved in measles protein-induced airway immune suppression.

BACKGROUND AND AIMS: Measles infection causes immune suppression that contributes to morbidity and mortality of the patients; the mechanism is poorly understood. Regulatory T cells (Treg) play a critical role in immune suppression. Integrin alphavbeta6 (avb6) is associated with Treg's function. This study aims to investigate into the mechanism by which measles C protein (MVP)-induced avb6 contributes the generation of Tregs in the lung. METHOD: MVP was introduced to mouse lung by nasal drops. The expression of avb6 by lung tissue was examined by reverse transcription polymerase chain reaction and Western blotting. The development of tolerogenic dendritic cells (DC) and Tregs in the lung and their functions was examined by flow cytometry. The suppressor function of MVP-induced Tregs was examined by cell culture models. RESULTS: The exposure to MVP markedly increased the expression of avb6 in the lung epithelial cells. Administration of MVP significantly suppressed the levels of IL-4 and IFNγ as well as increases in Tregs in lung tissue. DCs captured the MVP in the lung and differentiate into tolerogenic DCs; the latter has the ability to induce Treg development in the lung. Activation of MVP-induced Tregs powerfully suppressed polarized CD4(+) T cells. CONCLUSIONS: Exposure to MVP can induce Treg development in the lung that plays an important role in the suppression of CD4(+) T cell function.

Total enteral nutrition in prevention of pancreatic necrotic infection in severe acute pancreatitis.

OBJECTIVE: This study was designed to evaluate the effects of total enteral nutrition and total parenteral nutrition in prevention of pancreatic necrotic infection in severe acute pancreatitis. METHODS: One hundred seven patients were enrolled in the study between 2003 and 2007. In the first week of hospitalization, they were randomized to feeding by either total parenteral nutrition (54 patients) or total enteral nutrition (53 patients). All patients were concomitantly administered with sufficient prophylactic antibiotics. Computed tomographic scan and C-reactive protein level indicated a similar clinical severity in both groups. RESULTS: Eighty percent of the patients developed organ failure in the group with total parenteral nutrition, which was higher than that in the group with total enteral nutrition (21%). Eighty percent and 22% (P < 0.05) of the patients in the total parenteral nutrition and total enteral nutrition groups, respectively, underwent surgical intervention. The incidence of pancreatic septic necroses in the group with total enteral nutrition (23%) was lower than that in the group with total parenteral nutrition (72%, P < 0.05). Mortality in the total parenteral nutrition group (43%) was higher than in the total enteral nutrition group (11%, P < 0.05). CONCLUSION: Total enteral nutrition is better than total parenteral nutrition in the prevention of pancreatic necrotic infection in severe acute pancreatitis.

Increased superoxide radical with a decrease in vascular endothelial growth factor and inducible nitric oxide synthase level leads to the progression of left ventricular hypertrophy in a pressure-overload rat heart model.

PURPOSE: This study was designed to evaluate the relationship among free radicals and vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) during the progression of left ventricular hypertrophy (LVH) in pressure-overload rat heart. METHODS: Hypertrophied rat heart created by abdominal aortic banding at the age of 4 weeks was studied at the ages of 14, 15, 18, 21, 26, and 30 weeks (n=5 in each group). Free radicals were detected by an electron spin resonance (ESR) method using LV tissue. The levels of messenger ribonucleic acid (mRNA) for VEGF, superoxide dismutase (SOD), and iNOS in myocardium were analyzed by reverse transcription (RT)-polymerase chain reaction (PCR). RESULTS: Free radicals consisting of superoxide families increased over time after aortic banding and were highest in the 30-week group. The SOD mRNA level decreased with the progression of hypertrophy and was inversely proportional to the free radicals level. As compared to the control, the level of mRNA for VEGF and iNOS was significantly increased in 18-and 21-week hypertrophied hearts, but significantly decreased in 26-and 30-week hearts. CONCLUSION: The increased level of free radicals with the decrease of VEGF and iNOS levels may contribute to the progression of the pressure-overload hypertrophied heart to the failing heart.

Platelet preservation with a glycoprotein IIb/IIIa inhibitor in a porcine cardiopulmonary bypass model.

BACKGROUND: We tested whether administration of FK633, a short-acting glycoprotein IIb/IIIa inhibitor, before median sternotomy and cardiopulmonary bypass was able to interrupt the platelet activation loop and thereby preserve platelet number and function. METHODS: This study investigated 16 pigs that underwent median sternotomy and 120 minutes of normothermic cardiopulmonary bypass (100 mL/kg) adding pericardial blood to the perfusate. FK633 was administered with heparin to one group (group F, n = 8), whereas only heparin was administered to the control group (group C, n = 8). Blood samples were obtained at several times, and complete blood count, platelet aggregation to adenosine diphosphate, thrombin-antithrombin complex, and bradykinin were evaluated. P-selectin expression and fibrinogen binding on platelet surfaces were measured by flow cytometry. Template bleeding times were measured before and after cardiopulmonary bypass. Chest tube drainage and hematocrit were determined at 2 and 6 hours after cardiopulmonary bypass. RESULTS: In group F, platelet counts were preserved from 90 minutes of cardiopulmonary bypass. Platelet aggregation was inhibited at the beginning of cardiopulmonary bypass and showed no change at wound closure, and bleeding times were shortened at 2 hours after cardiopulmonary bypass. There were significant reductions in hematocrit of drainage. Flow cytometry showed no changes in P-selectin expression and fibrinogen binding in group F, whereas P-selectin expression and fibrinogen binding were elevated in group C. CONCLUSIONS: Platelet inhibition with FK633 before invasive surgical procedure preserved platelet counts during and after cardiopulmonary bypass, and produced normal or near-normal bleeding times in the immediate postoperative period.

Surgical repair for chronic traumatic thoracic aneurysm after 12-year follow-up.

A 39-year-old man underwent surgical repair of chronic traumatic thoracic aneurysm after 12-year follow-up at our hospital. Eighteen years prior to surgery, he had been involved in a traffic accident, suffering a left hemopneumothorax. Chronic traumatic thoracic aneurysm is extremely rare that few guidelines for surgical intervention exist for this disorder. However, it has been observed that all patients with new symptoms should be operated promptly, and that asymptomatic aneurysm detected over 2 years after the initial trauma can be monitored by careful follow-up pending symptomatic or radiologic change. The present case provides additional support for these strategies.