G1 cell cycle arrest signaling in hepatic injury after intraperitoneal sepsis in rats.

OBJECTIVE AND DESIGN: Hepatocytes emerge from a quiescent state into a proliferative state to recover from septic injury. We hypothesize that hepatocyte cell cycle regulation after sepsis potentially contributes to the recovery of liver function. METHODS: An animal model of sepsis was induced by cecal ligation and puncture (CLP) in rats. At serial time points after CLP, hepatocyte expression of p21, P53, cyclin D1, cyclin E, CDK2, CDK4 and PCNA was determined by immunoblot analysis, and the DNA content of isolated hepatocytes was analyzed using flow cytometry. RESULTS: Sepsis-induced liver injury of rats was associated with G1 cell cycle arrest. Recovery of liver function was related to cell cycle progression 48 h after CLP. The upregulation of p53 and p21 correlated with G1 cell arrest 48 h after CLP. The upregulation of cyclin D1/CDK4 and cyclin E/CDK2 also correlated with the G1/S transition 48 h after CLP, resulting in PCNA expression. CONCLUSIONS: The data suggests that G1 cell cycle arrest and p53, p21, CDKs, cyclins and PCNA expression may be involved in the injury/recovery of liver function after intraperitoneal sepsis.

[The clinical significance of Aspergillus isolation from airway samples in critically ill patients].

OBJECTIVE: To analyze the risk factors and clinical significance of Aspergillus isolation from airway samples of critically ill patients. METHODS: The study was conducted in an ICU between January 2007 and December 2007. The data of patients receiving mechanical ventilation with suspected invasive pulmonary fungal infection were analyzed. Tracheal aspirates were collected and cultured 3 times weekly. The cases were classified into groups of Aspergillus spp, Candida spp, and non-fungus spp according to the microbiological results. Isolation of Aspergillus spp. was subgrouped to proved-IPA (invasive pulmonary aspergillosis), probable-IPA or colonization. The risk factors for airway isolation of Aspergillus and infection were assessed. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) for Windows (version 12.0) and quantitative variables were expressed as mean +/- standard deviation. The Student' s t-test or the Mann-Whitney U-test was used for the comparison of categorical and normally distributed and non normally distributed variables, respectively. The chi2 test or the Fisher's exact test was used in the comparison of categorical variables. Logistic regression analysis was conducted to evaluate risk factors for the isolation of Aspergillus spp. RESULTS: The study population included 160 patients (82 men) with a mean age of (64.5 +/- 17.2) years. Aspergillus spp was isolated in 45, Candida spp in 63, and non-fungus spp in 52. The ICU mortality in the 3 groups was 48.9% (22/45 cases), 23.8% (15/63 cases), 7.7% (4/52 cases), respectively. The ICU mortality in patients with Aspergillus spp. isolation was higher than those with Candida spp and non-fungus spp. In 28 patients isolation of Aspergillus spp. was interpreted as invasive aspergillosis (2 patients were proven, 26 patients were probable). The predictive value of isolating Aspergillus from airway samples was 62% (28/45 cases). On multivariate analysis, the following factors were independently associated with Aspergillus spp. isolation: connective tissue diseases (OR 3.3, 95% CI 1.7 - 12.2, chi2 = 4.82, P<0.01), hepatic dysfunction (OR 8.1, 95% CI 1.7 - 15.2, chi2 = 19.2, P<0.01), corticosteroid use (OR 4.6, 95% CI 2.6 - 13.7, chi2 = 8.92, P<0.01) and continuous renal replacement therapy (CRRT) (OR 5.1, 95% CI 2.6 - 11.5, chi2 = 11.4, P<0.01). Higher APACHE II score (25 +/- 6, 14 +/- 8, t = 2.75, P<0.01), septic shock (57%, 27%, chi2 = 3.56, P<0.01), and prolonged use of broad-spectrum antibiotics (15.9 d, 9.2 d, t = 2.49, P<0.01) were significantly associated with Aspergillus infection as compared to colonization. CONCLUSION: Critically ill patients with Aspergillus from airway samples had a higher mortality. Connective tissue diseases, hepatic dysfunction, corticosteroid use and CRRT were significantly associated with Aspergillus spp. isolation in critically ill patients. In severely ill patients, the isolation of Aspergillus is highly indicative of infection rather than colonization.

Acute renal failure during sepsis: potential role of cell cycle regulation.

OBJECTIVES: This study aimed to evaluate cell cycle regulation in acute kidney injury after intraperitoneal sepsis in rats. METHODS: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in rats. At 0, 6, 12, 24, 48, and 72 h after CLP, serum creatinine was evaluated. DNA content of isolated kidney cells was analyzed using flow cytometer. Furthermore, the expression of p21, p53, cyclin D1, cyclin E, CDK2, CDK4 and P-pRb was also measured by western blot. RESULTS: After sepsis-induced by CLP, kidney injury of rat was associated with G1 cell cycle arrest, however, recovery of renal function related to cell cycle progression 48h after CLP. Results also showed that the upregulation of p53 and p21 was correlated with G1 cell arrest in 48h after CLP. Nevertheless, upregulation of cyclin D1/CDK4 and cyclin E/CDK2 induced pRb phosphorylation, which resulted in the G1/S transition 48 h after CLP. CONCLUSION: The data suggest that G1 cell cycle arrest may play a role in the initiation of kidney injury, whereas, through regulating cell cycle, p53, p21, CDKs, cyclins and P-pRb may be involved in the injury or recovery of renal function after intraperitoneal sepsis.

[Preparation and characterization of poly-Si films on different topography substrates by AIC].

Polycrystalline silicon (poly-Si) thin-films were made on planar and textured glass substrates by aluminum-induced crystallization (AIC) of in situ amorphous silicon (a-Si) deposited by DC-magnetron. The poly-Si films were characterized by Raman spectroscopy, X-ray diffraction (XRD) and atomic force microscopy (AFM). A narrow and symmetrical Ranman peak at the wave number of about 521 cm(-1) was observed for all samples, indicating that the films were fully crystallized. XRD results show that the crystallites in the authors' AIC poly-Si films were preferably (111) oriented. The measurement of full width at half maximum (FWHW) of (111) XRD peaks showed that the quality of the films was affected by the a-Si deposition temperature and the surface morphology of the glass substrates. It is likely that an a-Si deposition temperature of 200 degrees C seems to be ideal for the preparation of poly-Si films by AIC.

[Early changes in function of hypothalamic-pituitary-target gland axis in patients with severe sepsis and septic shock].

OBJECTIVE: To investigate the early changes in function of hypothalamic-pituitary-target gland (HPTG) axis in patients with severe sepsis and septic shock, in order to clarify its relationship with severity and prognosis of the patients. METHODS: The serum contents of cortisol (F), triiodothyronine (T(3)), thyroxine (T(4)), thyrotropic-stimulating hormone (TSH), growth hormone (GH), follicle-stimulating hormone (FSH), luteotropic hormone (LH), prolactin (PRL) and plasma concentration of adrenocorticotrophic hormone (ACTH) in 10 severe sepsis and 12 septic shock patients on day 1, 3, 5 after diagnosis was made, and 12 patients with no infection or septic shock served as controls. The hypothalamic-pituitary adrenal gland axis (HPAA) function of the patients with severe sepsis and septic shock were evaluated with 1 microgram ACTH stimulation test given 1 day after the concentrations of the above hormones were determined. RESULTS: Compared with the control patients, ACTH, T(3), T(4), GH, FSH, LH and PRL levels were significantly changed in patients with severe sepsis and septic shock (P<0.05 or P<0.01). The numbers of patients with reaction to 1 microgram ACTH stimulation test were similar between patients with severe sepsis (6 cases non-reaction and 3 cases reaction) and patients with septic shock (9 cases non reaction and 2 cases reaction, P>0.05). According to the acute physiology and chronic health evaluation II (APACHE II) and sepsis-related organ failure assessment (SOFA) score, changes in ACTH, T(3), T(4), GH and PRL levels were closely related to the severity of illness (P<0.05 or P<0.01). Significant differences were found in ACTH, T(3), T(4) levels between survivors and non-survivors (P<0.05 or P<0.01). ACTH, T(4) levels and SOFA score were independent predictors of the 28-day hospital mortality (P<0.05 or P<0.01). CONCLUSION: The early changes in HPTG axis are closely related with the severity and hospital mortality in patients with severe sepsis and septic shock.

[The application of individualized ventilation strategies in acute respiratory distress syndrome].

OBJECTIVE: To explore better ventilation strategies above lower-tidal-volume (LTV) strategy to protect lung function and improve outcome in acute respiratory distress syndrome (ARDS). METHODS: Thirty ARDS patients were enrolled in Department of Critical Care Medicine of Peking Union Medical College Hospital from July, 2004 to June, 2005. They were randomly allocated into two groups, LTV group and individual ventilation (IV) group. Patients received 6 ml/kg tidal volume (V(T)) and high positive end-expiratory pressure (PEEP) in LTV group. In IV group, static pressure-volume (P-V) curve was measured daily, and PEEP and V(T) were set based on P-V variation, and the open-lung potential was evaluated before recruitment maneuvers. The clinical effect, the degree of lung injury and other outcome indicators in two groups were assessed. RESULTS: The mortality rate in 28 days of IV group (35.7%) was lower than that of LVT group (57.2%, chi(2) = 1.265, P > 0.05). The serum surfactant-associated protein D (SP-D) expression in the third and the seventh day of IV group [154 (91 - 217), 149 (91 - 206) mg/L] were higher than those before enrollment [140 (80 - 200) mg/L]; and the IL-8 expression in the third and the seventh day of IV group [179 (122 - 236), 210 (100 - 321) ng/L] were higher than those before enrollment [210 (132 - 289) ng/L]; but all showed no significant difference [chi(2) = 1.265, Z = 1.079, 1.741, -0.879, 0.471, respectively, all P > 0.05]. The free-ICU days in 28 days and free-organ-dysfunction days of IV group [11 (5 - 16) d, 13 (6 - 18) d] were significantly higher than that of LTV group [3 (0 - 8) d, 3 (0 - 7) d, Z = -2.277, -2.372 respectively, all P < 0.05]. The PEEP, V(T), partial pressure of carbon dioxide in arterial blood (PaCO2), the plateau pressure (Pplat) of initial 3 days after enrollment in IV group [(11 +/- 2) cm H2O (1 cm H2O = 0.098 kPa), (511 +/- 66) ml, (37 +/- 5) mm Hg (1 mm Hg = 0.133 kPa), (21 +/- 5) cm H2O] were significant different with those of LTV group [(16 +/- 3) cm H2O, (407 +/- 58) ml, (47 +/- 8) mm Hg, (26 +/- 4) cm H2O, t = -8.019, 6.501, -4.311, -4.823, all P < 0.01]. CONCLUSIONS: Compared with LTV and high PEEP therapy, IV strategies are feasible for decreasing PEEP and Pplat, increasing tidal compliance and V(T), and avoiding CO2 retention. It also increased free-ICU days and free-organ-dysfunction days.

[Evaluation of the characteristic of alveolar recruitment and derecruitment with the static pressure-volume curve in rabbits with acute respiratory distress syndrome].

OBJECTIVE: To evaluate the value of static pressure-volume (P-V) curve during alveolar recruitment and derecruitment in mechanical ventilated rabbits with acute respiratory distress syndrome (ARDS), and to explore the lung protective ventilation strategies. METHODS: The ARDS rabbit model was duplicated by warm-saline alveolar lavage. Dynamic CT scan was implemented to monitor the intrapulmonary gas volume and distribution during alveolar recruitment and derecruitment gradually. Static P-V curve was measured to reflect the features of alveolar recruitment and derecruitment. RESULTS: Four aeration regions including nonaeration, insufficient aeration, normal aeration and overinflation regions, varied following airway pressure variation (t = 2.477 - 9.794, all P < 0.05). Recruitment of insufficient aeration region was found. Alveolar recruitment was divided two parts, alveolar open at nonaeration region and recruitment at insufficient aeration region. And alveolar derecruitment was divided two parts, alveolar close at nonaeration region and derecruitment at insufficient aeration region. Distribution frequency of alveolar open was different from inspiratory (r = 0.219, P = 0.220). And distribution frequency of alveolar close was different from expiratory (r = 0.094, P = 0.593). The compliance of P-V curve was only positively correlated with the volume of insufficient aeration region (inspiration r = 0.827, P = 0.006; expiration r = 0.792, P = 0.011). The airway pressure with the maximal compliance at inspiratory P-V curve [(16.2 +/- 3.5) cm H2O, 1 cm H2O = 0.098 kPa] was positively correlated with the alveolar opening pressure [(16.4 +/- 3.4) cm H2O, r = 0.900, P = 0.002], and the airway pressure with the maximal compliance at expiratory P-V curve [(11.9 +/- 2.4) cm H2O] was positively correlated with the alveolar closing pressure [(11.3 +/- 2.5) cm H2O, r = 0.887, P = 0.003]. CONCLUSIONS: During inspiration, alveolar recruitment takes place with alveolar overinflation. The compliance of P-V curve is correlated with insufficient region volume, and reflects the potential of lung recruitment, and can predict the alveolar opening pressure and closing pressure.