Modulation of IKKß/NF-κB and TGF-ß1/Smad via Fuzheng Huayu recipe involves in prevention of nutritional steatohepatitis and fibrosis in mice.

OBJECTIVES: Fuzheng Huayu recipe (FZHY) exerts significant protective effects against liver fibrosis by strengthening the body's resistance and removing blood stasis. However, the molecular mechanisms through which FZHY affects liver fibrosis are still unclear. In this study, we examined the expression levels of factors involved in the inhibitor κB kinase-ß (IKK-ß)/nuclear factor-κB (NF-κB) and transforming growth factor beta 1 (TGF-ß1)/Smad signaling pathways to elucidate whether FZHY could attenuate nutritional steatohepatitis and fibrosis in mice. MATERIALS AND METHODS: C57BL/6J mice were fed with methionine-choline deficient (MCD) diet for 8 weeks to induce fibrotic steatohepatitis. FZHY and/or heme oxygenase-1 (HO-1) chemical inducer (hemin) were administered to mice. The effects of FZHY alone and in combination with hemin were assessed by comparing the severity of hepatic injury, activation of hepatic stellate cells (HSCs), and the expression of oxidative stress, inflammation and fibrogenesis related genes. RESULTS: Administration of FZHY, hemin and FZHY plus hemin significantly ameliorated liver injury. Additionally, our analysis indicated that administration of these agents significantly attenuated oxidative stress, downregulated the expression of pro-inflammatory and pro-fibrotic genes, including IKK-ß, NF-κB, monocyte chemoattractant protein-1 (MCP-1), α-smooth muscle actin (α-SMA), TGF-ß1, Smad3 and Smad4, and upregulated the expression of the antifibrogenic gene Smad7 (P< 0.001). CONCLUSION: FZHY-containing therapies prevented nutritional steatohepatitis and fibrosis through modulating the expression of factors associated with the IKKß/NF-κB and TGF-ß1/Smad signaling pathways and oxidative stress related genes.

Serum miR-122 levels are related to coagulation disorders in sepsis patients.

BACKGROUND: Coagulation abnormalities may have a major impact on the outcome of sepsis in patients. This study aimed to explore the relationship between miRNA levels and coagulation disorders during sepsis. METHODS: Blood samples from 123 sepsis patients were collected on the day of admission and another 45 sepsis patients on days 1, 3, 5, 7, 10, and 14 following admission to the intensive care unit. miR-223, miR-15a, miR-16, miR-122, miR-193b*, and miR-483-5p levels were evaluated by quantitative reverse transcription polymerase chain reaction. Based on the International Society on Thrombosis and Haemostasis (ISTH) Disseminated Intravascular Coagulation (DIC) score, sepsis patients were divided into coagulation abnormal (CA) group and coagulation normal (CN) group. RESULTS: Only the levels of miR-122 were significantly higher in CA patients than in CN patients (p<0.001). Serum levels of miR-122 were correlated to the serum activated partial thromboplastin time (APTT) ratios (R=0.426, p=0.008) and the fibrinogen (FIB; R=0.398, p=0.008) and antithrombin III (R=0.913, p<0.001) levels. In addition, Pearson's correlation coefficients for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with miR-122 were 0.663 (p<0.001) and 0.445 (p=0.001), respectively. In the 45 patients, the miR-122 levels were significantly higher on day 1, 3, 7, and 10 in the CA group than in the CN group, and no difference in the ISTH-DIC scores was evident. CONCLUSIONS: Serum levels of miR-122 were correlated to the coagulation disorder in sepsis patients.

Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs.

The goal of the present study was to identify novel protein biomarkers from the target genes of six serum miRNAs that we identified previously in patients with sepsis. The target genes were predicted by bioinformatics analysis; the levels of the respective proteins in the sera of patients with sepsis were detected by ELISA. ACVR2A (activin A receptor, type IIA), FOXO1 (forkhead box O1), IHH (Indian hedgehog), STK4 (serine/threonine kinase 4) and DUSP3 (dual specificity phosphatase 3) were predicted to be the targets of the six miRNAs, and their encoded proteins were used for biomarker identification. Levels of ACVR2A (P<0.01) and FOXO1 (P<0.01) were significantly different among normal controls, patients with sepsis, patients with severe sepsis and patients with septic shock. Furthermore, levels of ACVR2A (P=0.025), FOXO1 (P<0.001), IHH (P=0.001) and STK4 (P=0.001) were differentially expressed in survivors and non-survivors. DUSP3 levels were not significantly different between any groups. Conjoin analysis of the four differentially expressed proteins showed that the area under the curve of the predictive probabilities was 0.875 [95% CI (confidence interval): 0.785-0.965], which was higher than the SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. When the value of predictive probabilities was 0.449, the four proteins yielded a sensitivity of 68% and a specificity of 91%. Dynamic changes in ACVR2A, FOXO1 and IHH levels showed differential expression between survivors and non-survivors at all time points. On the basis of a combined analysis of the four identified proteins, their predictive value of 28-day mortality of patients with sepsis was better than the SOFA or APACHE II scores.

[Assessment of prognostic and influencing factors in elderly patients with multiple organ dysfunction syndrome].

OBJECTIVE: To preliminarily assess the prognosis of patients with multiple organ dysfunction syndrome (MODSE) and analyze their influencing factors. METHODS: The clinical data of 365 MODSE patients admitted into Chinese PLA General Hospital during January 2009 to June 2012 were analyzed retrospectively. According to 28-day outcomes, they were divided into 2 groups (28-day survival and non-survival) while 4 groups according to age. Then these prognosis were evaluated with the current scoring systems ((acute physiology and chronic health evaluation II (APACHEII and III), sample acute physiological score (SAPSII) and multiple organ dysfunction score (MODS)). The predictive powers were compared by receiver operating characteristic (ROC) curve. Finally a binary Logistic regression analysis was performed to evaluate the relevant influencing prognostic factors of MODSE. RESULTS: The mean age was (77.8 ± 9.1) years, mean number of failed organs (3.6 ± 1.2) and a 28-day mortality 45.8%. The ages of non-survival group were older than those of survival group ((78.1 ± 9.1) vs (76.7 ± 11.0) years). The number of organ failures ((4.3 ± 1.1) vs (3.1 ± 1.0)) and scores (APACHEII: (28 ± 7) vs (20 ± 8), APACHE III: (106 ± 27) vs (75 ± 31), SAPSII: (64 ± 16) vs (46 ± 18), MODS: (9 ± 3) vs (6 ± 3)) of non-survivals were significantly higher than that of survivals. The area under ROC curve of these four score systems were 0.790, 0.781, 0.780 and 0.780 respectively. Compared to the above systems, SAPSII had the best performance in sensitivity while APACHEII was more valuable in specificity. All clinical data underwent binary Logistic regression and the results showed that plasma concentration of albumin and mean arterial pressure (MAP) offered beneficial outcomes while age and number of organ failures had unfavorable prognosis. The greater patient age, the higher their mortality. CONCLUSIONS: All four scoring systems have accurate prognostic predictions of MODSE patients. And the predictive power of APACHEII is the best. Plasma concentration of albumin, MAP, age and organ failure number are independent prognostic factors in MODSE patients.

[Study of using an individualized treatment strategy to treat patients with chronic hepatitis C].

OBJECTIVE: To investigate the outcomes of chronic hepatitis C (CHC) patients treated with antiviral regimens of interferon (IFN) plus ribavirin (RBV) using individualized doses and durations. METHODS: This study was designed as an open-label, prospective clinical trial to analyze the virological responses of 169 CHC patients who received individualized dosages of IFNa-2b or pegylated (Peg)IFNa-2a combined with RBV based on their weight ( less than 60 kg or more than or equal to 60 kg), age (less than 65 years or 65-75 years), morbid state (liver cirrhosis or not), and complications (such as heart disease, diabetes, thyroid disorder). Treatment duration was calculated using the time required to induce HCV RNA negativity. The rates of virological response and adverse effects among the different groups were compared. RESULTS: The IFNa-2b treatment was given to 116 patients, and PegIFNa-2a was given to 53 patients. Compared to the IFNa-2b group, the PegIFNa-2a group showed significantly higher rates of complete early virological response (cEVR; 76.7% vs. 92.5%, P less than 0.05) and sustained virological response (SVR; 53.6% vs. 92.3%, P less than 0.05) among the patients who had completed their course of treatment; the rapid virological response (RVR) rate was also higher for the PegIFNa-2a group but the difference did not reach statistical significance (48.7% vs. 60.4%, P more than 0.05). Seventy-eight patients received the routine dose, and 91 patients received the low dose; there were no significant differences between these two groups for RVR (53.8% vs. 58.9%, P more than 0.05), cEVR (78.0% vs. 80.8%, P more than 0.05), or SVR (65.5% vs. 58.3%, P more than 0.05). CONCLUSION: Use of an individualized antiviral treatment strategy designed according to the patient's baseline condition, early viral kinetics, and tolerability to adverse reactions can achieve a high rate of SVR, as well as improve the safety, prognosis, and cost-effectiveness associated with treating CHC patients.

Characterization and Identification of novel serum microRNAs in sepsis patients with different outcomes.

Circulating microRNAs (miRNAs) are an emerging biomarker for sepsis patients. The purpose of this study was to identify novel miRNAs in the sera of sepsis patients and determine their prognostic value. Ninety-four serum samples were collected from sepsis patients within 24 h of intensive care unit admission. Solexa sequencing followed by bioinformatics analysis was used to predict novel miRNAs in survivors (n = 9) and nonsurvivors (n = 9). A total of 650 novel miRNAs were predicted by bioinformatics analysis after Solexa sequencing, and 41 novel miRNAs were validated in 10 survivors, 10 nonsurvivors, and 10 healthy controls by quantitative reverse transcriptase-polymerase chain reaction. Among these 41 miRNAs, 18 were present in both survivors and nonsurvivors, and nine were differentially expressed between the two groups. The expression levels of the nine miRNAs were determined by quantitative reverse transcriptase-polymerase chain reaction in 24 nonsurvivors and 32 survivors, and six were differentially expressed. Conjoint analysis of the six miRNAs and severity scores (Acute Physiology and Chronic Health Evaluation II score and Sequential Organ Failure Assessment score) showed that the area under the receiver operating characteristic curve for the predictive value of the six miRNAs was 0.969 (95% confidence interval, 0.930-1.000). When the cutoff point was set at 0.714, the six miRNAs and severity score provided a sensitivity of 100% and a specificity of 82.6%. In conclusion, 41 novel miRNAs were detectable in the sera of sepsis patients, and six of them might be related to sepsis outcome.

Effects of vitamin b6 therapy for sepsis patients with linezolid-associated cytopenias: a retrospective study.

BACKGROUND: The common adverse effects of linezolid for treating septic patients with gram-positive cocci is anemia and thrombocytopenia, which limit its clinical application. OBJECTIVES: We determined the effects of vitamin B6 adjunctive therapy on linezolid-associated cytopenias, and retrospectively studied 75 septic patients who received at least 7 days of linezolid treatment. METHODS: Patients were divided into a linezolid treatment group (LTG; n = 41) that received linezolid only and a combination treatment group (CTG; n = 34) that received both linezolid and vitamin B6. Each group was further subdivided into those with sepsis and those with severe sepsis. Each patient had red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), and platelet (PLT) measurements at baseline (day 0) and every other day for 2 weeks during treatment; these parameters were compared between the groups and assessed for time-dependent trends. RESULTS: For patients in the LTG, RBC, Hb, and Hct values showed statistically significant reductions over time, and these values were lower compared with the values in the CTG. The CTG also showed downward trends, except on the first day of treatment. The PLT count also decreased in both groups. Patients with severe sepsis had lower PLT counts in both treatment groups compared with the septic patients. CONCLUSIONS: Septic patients who received a combination treatment of linezolid and vitamin B6 might show positive effects for linezolid-associated reductions in some hematologic parameters (RBC, Hb, and Hct). This combined treatment might also slow PLT reduction, which was more evident in patients with severe sepsis. ClinicalTrials.gov identifier: NCT01295801.

Diagnosing ventilator-associated pneumonia in critically ill patients with sepsis.

BACKGROUND: Timely diagnosis and prognostic assessment of ventilator-associated pneumonia remain major challenges in critical care. OBJECTIVE: To explore the value of soluble triggering receptor expressed on myeloid cells 1, procalcitonin, and the Clinical Pulmonary Infection Score in the diagnosis and prognostic assessment of ventilator-associated pneumonia. METHODS: For 92 patients, bronchoalveolar lavage fluid was cultured for detection of microorganisms, serum levels of the receptor and procalcitonin and levels of the receptor in exhaled ventilator condensate were measured, and the Clinical Pulmonary Infection Score was calculated. RESULTS: On the day of diagnosis, patients who had pneumonia had higher serum levels of the receptor, procalcitonin, and C-reactive protein; higher white blood cell counts; and higher pulmonary infection and Sequential Organ Failure Assessment scores than did patients without pneumonia. White blood cell count (odds ratio, 1.118; 95% CI, 1.139-1.204) and serum levels of the receptor (odds ratio, 1.002; 95% CI, 1.000-1.005) may be risk factors for VAP. Serum levels of the receptor plus the pulmonary infection score were the most reliable for diagnosis; the area under the receiver operating characteristic curve was 0.972 (95% CI, 0.945-0.999), sensitivity was 0.875, and specificity was 0.95. For 28-day survival, procalcitonin level combined with pulmonary infection score was the most reliable for prognostic assessment (area under the curve, 0.848; 95% CI, 0.672-1.025). CONCLUSIONS: In patients with ventilator-associated pneumonia, serum levels of the receptor plus the pulmonary infection score are useful for diagnosis, and procalcitonin levels plus the pulmonary infection score are useful for prognostic assessment.

Four serum microRNAs identified as diagnostic biomarkers of sepsis.

BACKGROUND: Serum microRNAs (miRNAs) can be used as biomarkers for many kinds of diseases, and some are even better than current indicators. The aim of this study was to investigate a diagnostic role for serum miRNAs in sepsis patients. METHODS: We recruited 166 patients with sepsis and 24 normal controls. Blood samples for these patients were obtained upon their admission in intensive care units of the Chinese PLA General Hospital. The expression levels of miR-223, miR-15b, miR-483-5p, miR-499-5p, miR-122, and miR-193b* were determined by quantitative reverse transcriptase polymerase chain reaction assays. RESULTS: Expression levels of miR-223 were significantly higher in patients with mild sepsis (p < 0.001) and patients with severe sepsis and septic shock (p < 0.001) than in normal controls, and levels of miR-499-5p, miR-122, and miR-193b* were significantly lower than in normal controls. In addition, only miR-223 (p = 0.035) and miR-499-5p (p < 0.001) were significantly different between patients with mild sepsis and patients with severe sepsis and septic shock. miR-499-5p had the highest area under a receiver operating characteristic curve of 0.686 (95% confidence interval, 0.592-0.779). In addition, Sequential Organ Failure Assessment scores (p < 0.001), Acute Physiology and Chronic Health Evaluation II scores (p < 0.001), and procalcitonin levels (p < 0.001) also could distinguish a mild sepsis group from a severe sepsis and septic shock group. In a binary logistic regression model, only miR-499-5p and Sequential Organ Failure Assessment scores had good diagnostic values to distinguish between mild sepsis and severe sepsis and septic shock. CONCLUSION: Four serum miRNAs were identified as novel biomarkers of sepsis. LEVEL OF EVIDENCE: II, diagnostic study.

Clinical significance of soluble hemoglobin scavenger receptor CD163 (sCD163) in sepsis, a prospective study.

OBJECTIVE: We investigated serum soluble CD163 (sCD163) levels for use in the diagnosis, severity assessment, and prognosis of sepsis in the critical ill patients and compared sCD163 with other infection-related variables. METHODS: During july 2010 and April 2011, serum was obtained from 102 sepsis patients (days 1, 3, 5, 7, and 10 after admission to an ICU) and 30 systemic inflammatory response syndrome (SIRS) patients with no sepsis diagnosed. Serum levels of sCD163, procalcitonon (PCT), and C reactive protein (CRP) were determined respectively. Sequential organ failure assessment (SOFA) scores for sepsis patients were also recorded. Then evaluated their roles in sepsis. RESULTS: The sCD163 levels were 0.88(0.78-1.00) ug/mL for SIRS patients, 1.50(0.92-2.00) ug/mL for moderate sepsis patients, and 2.95(2.18-5.57) ug/mL for severe sepsis patients on day 1. The areas under the ROC curves for sCD163, CRP, and PCT for the diagnosis of sepsis were, respectively, 0.856(95%CI: 0.791-0.921), 0.696(95%CI: 0.595-0.797), and 0.629(95%CI: 0.495-0.763), At the recommended cut-off 1.49 ug/mL for sCD163, the sensitivity is 74.0% with 93.3% specificity. Based on 28-day survivals, sCD163 levels in the surviving group stay constant, while they tended to gradually increase in the non-surviving group.The area under the ROC curve for sCD163 for sepsis prognosis was 0.706(95%CI 0.558-0.804). Levels of sCD163 with cut-off point >2.84 ug/mL have sensitivity of 55.8.0%, specificity 80.4%. Common risk factors for death and sCD163 were included in multivariate logistic regression analysis; the odds ratios (OR) for sCD163 and SOFA scores for sepsis prognosis were 1.173 and 1.396, respectively (P<0.05). Spearman rank correlation analysis showed that sCD163 was weakly, but positively correlated with CRP, PCT, and SOFA scores (0.2< r <0.4, P<0.0001), but not with leukocyte counts (r <0.2, P = 0.450). CONCLUSION: Serum sCD163 is superior to PCT and CRP for the diagnosis of sepsis and differentiate the severity of sepsis. sCD163 levels were more sensitive for dynamic evaluations of sepsis prognosis. Serum sCD163 and SOFA scores are prognostic factors for sepsis. TRIAL REGISTRATION: www.chictr.orgChiCTR-ONC-10000812.

Fuzheng Huayu recipe prevents nutritional fibrosing steatohepatitis in mice.

BACKGROUND: Fuzheng Huayu recipe (FZHY), a compound of Chinese herbal medicine, was reported to improve liver function and fibrosis in patients with hepatitis B virus infection. However, its effect on nutritional fibrosing steatohepatitis is unclear. We aimed to elucidate the role and molecular mechanism of FZHY on this disorder in mice. METHODS: C57BL/6 J mice were fed with methionine-choline deficient (MCD) diet for 8 weeks to induce fibrosing steatohepatitis. FZHY and/or heme oxygenase-1 (HO-1) chemical inducer (hemin) were administered to mice, respectively. The effect of FZHY was assessed by comparing the severity of hepatic injury, levels of hepatic lipid peroxides, activation of hepatic stellate cells (HSCs) and the expression of oxidative stress, inflammatory and fibrogenic related genes. RESULTS: Mice fed with MCD diet for 8 weeks showed severe hepatic injury including hepatic steatosis, necro-inflammation and fibrosis. Administration of FZHY or hemin significantly lowered serum levels of alanine aminotransferase, aspartate aminotransferase, reduced hepatic oxidative stress and ameliorated hepatic inflammation and fibrosis. An additive effect was observed in mice fed MCD supplemented with FZHY or/and hemin. These effects were associated with down-regulation of pro-oxidative stress gene cytochrome P450 2E1, up-regulation of anti-oxidative gene HO-1; suppression of pro-inflammation genes tumor necrosis factor alpha and interleukin-6; and inhibition of pro-fibrotic genes including α-smooth muscle actin, transforming growth factor beta 1, collagen type I (Col-1) and Col-3. CONCLUSIONS: Our study demonstrated the protective role of FZHY in ameliorating nutritional fibrosing steatohepatitis. The effect was mediated through regulating key genes related to oxidative stress, inflammation and fibrogenesis.

Diagnostic value of urine sTREM-1 for sepsis and relevant acute kidney injuries: a prospective study.

INTRODUCTION: We explored the diagnostic value of a urine soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for early sepsis identification, severity and prognosis assessment, and for secondary acute kidney injury (AKI). We compared this with white blood cell (WBC) counts, serum C-reactive protein (CRP), serum procalcitonin (PCT), urine output, creatinine clearance (CCr), serum creatinine (SCr), and blood urea nitrogen (BUN). METHODS: We enrolled 104 subjects admitted to the ICU: 16 cases with systemic inflammatory response syndrome (SIRS); 35 with sepsis and 53 with severe sepsis. Results for urine sTREM-1, WBC, serum CRP and serum PCT were recorded on days 1, 3, 5, 7, 10, and 14. For 17 sepsis cases diagnosed with secondary AKI, comparisons between their urine sTREM-1, urine output, CCr, SCr and BUN at diagnosis and 48 h before diagnosis were made. RESULTS: On the day of admission to the ICU, and compared with the SIRS group, the sepsis group exhibited higher levels of urine sTREM-1 and Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) scores (P < 0.05). Areas under the curve (AUC) shaped by the scores were 0.797 (95% CI 0.711 to 0.884) and 0.722 (95% CI 0.586 to 0.858), respectively. On days 1, 3, 5, 7, 10, and 14, urine sTREM-1, serum PCT and WBC levels registered higher in the severe sepsis group in contrast to the sepsis group (P < 0.05). Urine sTREM-1 and serum PCT levels continuously increased among non-survivors, while WBC and serum CRP levels in both groups declined. For 17 patients with AKI, urine sTREM-1, SCr and BUN levels at 48 h before AKI diagnosis were higher, and CCr level was lower than those for non-AKI subjects (P < 0.05). AUC for urine sTREM-1 was 0.922 (95% CI 0.850 to 0.995), the sensitivity was 0.941, and the specificity was 0.76 (based on a cut-off point of 69.04 pg/ml). Logistic regression analysis showed that urine sTREM-1 and severity were risk factors related to AKI occurrence. CONCLUSIONS: Besides being non-invasive, urine sTREM-1 testing is more sensitive than testing WBC, serum CRP, and serum PCT for the early diagnosis of sepsis, as well as for dynamic assessments of severity and prognosis. It can also provide an early warning of possible secondary AKI in sepsis patients. TRIAL REGISTRATION: ClinicalTrial.gov identifier NCT01333657.

[Clinical analysis of non-invasive positive pressure ventilation in immunocompromised host with acute respiratory failure].

OBJECTIVE: To evaluate the value of non-invasive positive pressure ventilation (NPPV) in immunocompromised host (ICH) complicated by acute respiratory failure (ARF), and to investigate predictive variables of success with NPPV in ICH with ARF. METHODS: A retrospective study of immunocompromised patients with ARF, who were admitted to respiratory intensive care unit (RICU) from March 2008 to March 2011, was performed. Based on clinical data, univariate Logistic regression was done for prediction for independent factors affecting the success of NPPV treatment. Immunization status was assessed according to clinical outcome. RESULTS: NPPV was instituted in all 33 cases with ARF initially. Among these patients, 9 patients (27.3%) received sequential invasive mechanical ventilation (IMV, failure group) and all of them died finally; among 24 cases (72.7%) who only received NPPV (success group), 7 patients died (29.2%). There was significant difference between the two groups in mortality (P<0.01). The simplified acute physiology scoreII (SAPSII) in the success group was lower than that in the failure group (33±9 vs. 43±5, P<0.01). However, other clinical data showed no statistical significance between two groups. Univariate Logistic regression analysis identified SAPSII was the independent factor associated with the success of NPPV treatment [odds ratio (OR) =0.83, 95% confidence interval (95% CI) 0.709-0.964, P<0.05]. And SAPSII≥38 was a risk factor for the failure of NPPV [area under receiver operating characteristic (ROC) curve 0.73]. In addition, the lung injury scores (LIS) in the survival group was significantly lower than that of the death group (1.95±0.48 vs. 2.57±0.52, P<0.01), the difference was statistically significant. CD3(+) and CD8(+) T counts in the survivors were higher than that of non-survivors (CD3(+):0.73±0.16 vs. 0.41±0.20; CD8(+): 0.51±0.18 vs. 0.21±0.15, both P<0.01), and the difference was statistically significant. CONCLUSION: As an early treatment for ICH with pulmonary infections suffering from ARF, NPPV can be effective for the ICH patients suffering from severe pulmonary infection through improving hypoxemia, ameliorating respiratory distress symptoms, and avoiding complications associated with IMV when SAPSIIis less than 38. CD3(+), CD8(+), and the LIS can be used to evaluate the prognosis of those patients.

Tri-phasic modulation of ACh- and NA-maintained calcium plateau by high potassium in isolated mouse submandibular granular convoluted tubular cells.

OBJECTIVES: The fact that submandibular glands secrete a large amount of potassium ion upon nerve stimulation has long been recognized, but a physiological role for such high potassium in the saliva has never been systematically investigated. In the present work, high potassium effect has been investigated in the freshly isolated mouse submandibular granular convoluted tubules. DESIGN: Isolated intact mouse submandibular granular convoluted tubules were loaded with Fura-2, and cytosolic calcium concentration in individual tubular cells was measured by microscopic fluorospectrometry. RESULTS: It was found that high potassium had no effect on basal cytosolic calcium concentration, but had a tri-phasic modulation of the calcium plateau maintained by continued stimulation by acetylcholine (ACh) or noradrenaline (NA): a minor initial transient depression, followed by steady increase, completed by a robust calcium rebound spike upon removal of high potassium. The phase of steady increase was blocked without major effect on the plateau by KB-R 7943, a sodium/calcium exchange (NCX) inhibitor. CONCLUSION: These data together suggest that high potassium in saliva bathing the mouse submandibular granular convoluted tubular cells has a potent feedback effect on ACh and NA stimulation, and sodium/calcium exchange is likely to play a major role in this process. Such positive feedback actions of high potassium may suggest a role for enhancing ACh- or NA-stimulated protein factor secretion from the granulated convoluted tubular cells.

The continuous accumulation of Na+ in detached leaf sections is associated with over-expression of NTHK1 and salt tolerance in poplar plants.

Detached leaf sections (2×2cm2) from transgenic poplar line 18-1 and its wild type (WT) (Populus× euramericana 'Neva') were used to test their salt tolerance and gene expression under controlled environment conditions. The sections from line 18-1 displayed better tolerance to NaCl stress, indicated by high chlorophyll retention and K+ content but low relative electrolyte leakage (REL). Transient overexpression of NTHK1 (Nicotiana tabacum histidine kinase 1) and V-H+-PPase was found in the detached young leaves from line 18-1 after they had been stressed for a few minutes. The activities of vacuolar-type H+-ATPase and H+-PPase in line 18-1 were boosted initially and then decreased to normal level as in unstressed leaves. After sections were stressed for 10 days, the maximal Na+ concentration in line 18-1 was much higher than that in the WT. The higher capacity for Na+ accumulation in line 18-1 may be due to stable Na+ sequestration into the vacuoles. Osmotic stress imposed little effect on REL and chlorophyll content of the sections. The capacity of detached leaf sections in NaCl solution to tolerate stress and to accumulate Na+ may be useful for identifying genotypes with good salt tolerance in poplar and other plants.

[Dynamic changes of groundwater level and vegetation in water table fluctuant belt in lower reaches of Heihe River: coupling simulation].

Based on the 2006 investigation data in lower reaches of Heihe River, and by using logarithmic normal distribution model, the models about the vegetation cover of Populus euphratica and Tamarix ramossima and the groundwater level in study area were built, and the potential plant of the study area was simulated. The results showed that in the lower reaches of Heihe River, the optimal groundwater level and mean groundwater level for P. euphratica were 2.6 m and 3.6 m, and those for T. ramossima were 2.0 m and 3.0 m, respectively. The high cover P. euphratica distribution area was mainly concentrated in the near-banks of Donghe River and Xihe River, while higher cover T. ramossima was distributed in most parts of the study area. From the aspect of current groundwater level, T. ramossima should be the adaptive species in the study area. The similarities between the potential and actual spatial distribution of P. euphratica and T. ramossima were 43. 4% and 55. 6% , respectively, and the main reason for the lower similarity was that there existed a gypsum salt pan in soil, which blocked the vertical movement of soil water.

Cytosolic calcium oscillations in submandibular gland cells.

Calcium oscillations can, by default, encode diverse and specific signals by different modes of modulation. Frequency modulation is illustrated by the activation of calcium/calmodulin-dependent protein kinase II at unit Hz, and of calcineurin at 10 mHz frequencies, respectively. The submandibular gland secretory axis is characterized by both potassium and osmolarity gradients from the luminal side of the secretory cells. Such gradients may play significant physiological roles through the feedback modulation of cholinergic stimulation. High potassium transforms plateau calcium increases induced by cholinergic stimulation of the submandibular acinar cells into oscillatory calcium increases. The ductal cells may have similar mechanisms of feedback modulation both by high potassium and by hypoosmolarity. Such feedback mechanisms could modulate the decision-making process for determining which secretory products are selectively released after nerve stimulation.

Aspiration of dead space in the management of chronic obstructive pulmonary disease patients with respiratory failure.

INTRODUCTION: Carbon dioxide clearance can be improved by reducing respiratory dead space or by increasing the clearance of carbon-dioxide-laden expiratory gas from the dead space. Aspiration of dead space (ASPIDS) improves carbon dioxide clearance by suctioning out (during expiration) the carbon-dioxide-rich expiratory gas while replacing the suctioned-out gas with oxygenated gas. We hypothesized that ASPIDS would allow lower tidal volume and thus reduce exposure to potentially injurious airway pressures. METHODS: With 8 hemodynamically stable, normothermic, ventilated patients suffering severe chronic obstructive pulmonary disease we tested the dead-space-clearance effects of ASPIDS. We compared ASPIDS to phasic tracheal gas insufflation (PTGI) during conventional mechanical ventilation and during permissive hypercapnia, which was induced by decreasing tidal volume by 30%. The mean P(aCO(2)) reductions with PTGI flows of 4.0 and 6.0 L/min and during ASPIDS (at 4.0 L/min) were 32.7%, 51.8%, and 53.5%, respectively. Peak, plateau, and mean airway pressure during permissive hypercapnia were significantly lower than during conventional mechanical ventilation but PTGI increased peak, plateau, and mean airway pressure. However, pressures were decreased during permissive hypercapnia while applying ASPIDS. Intrinsic positive end-expiratory pressure also increased with PTGI, but ASPIDS had no obvious influence on intrinsic positive end-expiratory pressure. ASPIDS had no effect on cardiovascular status. CONCLUSIONS: ASPIDS is a simple adjunct to mechanical ventilation that can decrease P(aCO(2)) during conventional mechanical ventilation and permissive hypercapnia.