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ABSTRACT: To investigate the influence of lactate Ringer solution (RL) versus hydroxyethyl starch 130/0.4 (HES130/0.4) solution on coagulation and fibrinolytic system in the patients with septic shock.
Forty-two consecutive patients with septic shock diagnosed between September 2009 and June 2011 were randomized to two study groups: RL resuscitation group (RL group) with 20 patients, and HES130/0.4 resuscitation group (HES group) with 22 patients. In all of them peripheral blood was collected at four points of time: before resuscitation, 6, 12, 24 hours after resuscitation, and then prothrombin time (PT), activated partial thromboplastin time (APTT) and levels of plasma tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI) were determined. Meanwhile, the patients' outcome and the length of intensive care unit stay (ICU-LOS) were recorded.
ICU-LOS (days) in HES group was significantly shorter than the RL group (12.5 ± 8.8 vs. 17.1 ± 16.6, P < 0.01). Meanwhile, the volume of fluid (L: 2.77 ± 0.59) as well as vasoactive drugs [μg×kg(-1)×min(-1): 0.56 ± 0.15] used in the HES group were significantly lower than RL group (3.46 ± 0.73, 0.81 ± 0.41, both P < 0.01). In RL group, 12 patients died and 8 patients survived, while in HES group, 7 patients died and 15 patients survived, showing no difference between two groups. PT, APTT and the levels of t-PA showed no significant differences between two groups at different time points, but the levels of plasma PAI (μg/L) of the HES group decreased gradually, and was significantly lower than that before resuscitation and RL group at 24 hours after resuscitation (41.76 ± 25.95 vs. 89.11 ± 14.27, 55.08 ± 35.43, both P < 0.05).
Both RL and HES130/0.4 fluid resuscitation did not affect the outcome of the patients with septic shock, but the resuscitation efficiency of HES130/0.4 is much better than RL. Both type of fluids did not show the effect on coagulability of the septic patients, but colloid fluid resuscitation may protect the vascular endothelial cell, reduce the inhibition of fibrinolytic system, and alleviate hypercoagulability state of patients in early stage.
Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 01/2012; 24(1):38-41.
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ABSTRACT: To evaluate the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with severe sepsis and septic shock.
In a prospective study, clinical data of 50 patients with severe sepsis and septic shock were analyzed. Plasma NT-proBNP level was measured at 0, 24, 48 and 72 hours after admission to the intensive care unit (ICU) of a university hospital. Patients were divided into survival group and non-survival group according to 30-day mortality rate. The dynamic variation of plasma NT-proBNP level was observed and the difference of plasma NT-proBNP levels between two groups was compared. The predictive value of NT-proBNP on mortality was evaluated by receiver operating characteristic (ROC) curves. The potential confounding factors on NT-proBNP were assessed with linear regression analysis.
NT-proBNP levels (μg/L)at 0 hour after admission to ICU [20.86(14.28,23.92)] were significantly higher in non-survival group (n=20) compared with survival group [ n=30, 10.02 (5.58, 16.41), P<0.01], and the difference persisted to 72 hours [19.68 (13.90, 24.02) vs. 9.24 (4.30, 11.81), P<0.01], but there was no statistical difference of NT-proBNP levels among four time points. In the ROC curves for NT-proBNP at admission, the area under the curve(AUC) for hospital mortality was 0.842, and 95% confidence interval (CI) was 0.764-0.922, P<0.01. NT-proBNP greater than 13.30 μg/L at admission was an independent indicator of mortality (sensitivity 80.6%, specificity 70.2%). Linear regression analysis revealed that the oxygenation index (PaO(2)/FiO(2), r=-0.839, P=0.003), platelet count (PLT, r=-0.803, P=0.032), and sequential organ failure assessment (SOFA) scores at 0 hour after admission to ICU (r=0.874, P<0.001) had independent effects on NT-proBNP values at admission.
Plasma NT-proBNP level is a valuable prognostic factor for severe sepsis and septic shock patients.
Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 08/2011; 23(8):467-70.
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ABSTRACT: To evaluate the value of B-type natriuretic peptide (BNP) in predicting the outcome of severe sepsis and septic shock patients.
One hundred and two patients with severe sepsis and septic shock were prospectively observed. Plasma BNP level was measured at 24th hour after admission to intensive care unit (ICU) of a university hospital. The data of clinical features, 28-day mortality, acute physiology and chronic health evaluation II (APACHE II) scores and the length of stay (LOS) in ICU were collected. The patients were divided into survival group and non-survival group. The survival group was further divided into BNP elevated group and BNP normal group.
APACHE II scores were significantly higher in non-survivors (39 patients) compared with survivors (63 patients, 28.9+/-5.9 vs. 20.2+/-5.4, P<0.01), but there were no statistical difference of white blood cell count and blood lactic levels between two groups. BNP levels were significantly higher in non-survivors compared with survivors [(1,451.3+/-531.7) ng/L vs. (394.5+/-81.7) ng/L, P<0.01]; BNP greater than 681.4 ng/L at first 24th hour was an independent indicator of mortality (sensitivity 91.4%, specificity 80.3%). In survivals, the LOS in ICU was significantly higher in BNP elevated group (48 patients) than BNP normal group [15 patients, (23.7+/-7.5) days vs. (14.9+/-5.1) days, P<0.05), but APACHE II scores showed no statistical difference between two groups.
Plasma BNP level is a valuable prognostic factor for severe sepsis and septic shock patients.
Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 05/2009; 21(5):293-5.
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ABSTRACT: To determine the diagnostic value of pulmonary function testing in Chinese patients with known pulmonary arterial hypertension (PAH) without history of lung/heart valve diseases.
Pulmonary function testing was performed in 41 PAH patients diagnosed by right heart catheterization and in 17 healthy controls.
Normal pulmonary function testing results were found in 5 PAH patients (12.2%). Total lung capacity, vital capacity and FEV1 were significantly decreased in PAH patients [(80.27 +/- 11.46)% vs. (94.24 +/- 6.82)%; (79.09 +/- 14.89)% vs. (97.35 +/- 9.51)%; (75.40 +/- 16.58)% vs. (95.12 +/- 12.01)%, respectively, all P < 0.001], the ratio of residual volume/total lung capacity was significantly increased [(117.67 +/- 25.73)% vs. (93.39 +/- 10.87)%, P < 0.001]; FEV1/FVC and maximal expiratory flow of 25% to 75% tended to be lower (-6.0% and -19.4%, P = 0.21 and 0.09) while DLCO and DLCO/VA were significantly decreased by 36.6% and 29.8% (P < 0.001) compared with healthy controls.
Increased peripheral airway obstruction and normal lung resistance were found in these PAH patients. Normal pulmonary function testing results could not rule out the diagnosis of PAH.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 01/2008; 36(1):3-6.
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ABSTRACT: Most physicians in China may neglect portal vein thrombosis (PVT) in clinical practice. In fact, portal vein thrombosis is an important cause of non-cirrhotic portal hypertension. As the diversity of its clinical manifestations, misdiagnosis is common if we donot bear PVT in mind during differential diagnosis. Therefore, we systematically reviewed PVT in terms of etiology, pathophysiology, pathology, clinical manifestations, and management.
An English language literature search (from 1980 to 2004) was performed using Medline and Medscape, and articles closely related to PVT were selected.
PVT is the second cause of portal hypertension after liver cirrhosis in western countries. Liver cirrhosis and hepatocellular carcinoma, intra-abdominal infection, thrombophilic disorders including myeloproliferative diseases are strongly associated with the development of PVT. Liver transplantation is an emerging etiological factor of PVT with the development and wide use of this technique. Gastrointestinal bleeding resulted from esophageal varices, abdominal pain, splenomegaly and hypersplenism and ascites are common manifestations of PVT. However there are differences in etiological and clinical presentations between children and adults. Diagnosis of PVT depends on imaging studies including Doppler ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and portography. Endoscopic therapy is recommended for variceal bleeding in PVT. Anticoagulant treatment for acute PVT is widely accepted in western countries.
PVT may be unrecognized as the clinical manifestations are unspecific. Misdiagnosis and delayed treatment can lead to poor prognosis. Systematical collection of epidemiological and clinical data about PVT is necessary in China.
Hepatobiliary & pancreatic diseases international: HBPD INT 12/2005; 4(4):515-8. · 1.08 Impact Factor
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ABSTRACT: To investigate the role and mechanism of endothelium-derived hyperpolarizing factor (EDHF) in shear stress induced vasorelaxation of rat mesenteric artery.
The changes in vessel diameter in response to variable flow (0-300 microL.min(-1)) were continuously examined. The contribution of prostacyclin (PGI2), NO and EDHF to shear stress induced relaxation were analyzed by inhibitory effects of indomethacin, N(G)-nitro-L-arginine (L-NA) and KCl. The nature and hyperpolarizing mechanism of EDHF were examined by the inhibitory effects of inhibitors of cytochrome P450 pathway and of various K+ channels.
The shear stress-induced relaxation were endothelium dependent and the contribution of NO was more prominent in large mesenteric arteries (400-500 microm) than that in resistance arteries (150-250 microm), whereas that of EDHF was noted in both-sized blood vessels. Tetrabutylammonium (a nonselective inhibitor of K channels) almost abolished, whereas the combination of charybdotoxin (an inhibitor of both large and intermediate-conductance Ca2+-activated K channels) and apamin (an inhibitor of small-conductance Ca2+-activated K channels) significantly inhibited the EDHF-mediated component of the shear stress-induced relaxations.
EDHF plays an important role in shear stress-induced endothelium-dependent relaxations, and K channels especially calcium-activated K channels appear to be involved.
Yao xue xue bao = Acta pharmaceutica Sinica 07/2005; 40(6):491-5.
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ABSTRACT: To investigate the effect of iontophoresis on skin permeation of defibrase.
Iontophoresis was carried out in side-by-side chambers, excised rat skin membrane (RSM) or human epidermis membrane (HEM). The effects of electrode polarity, permeation medium pH and ionic strength were evaluated.
Permeation of defibrase caused by anodal iontophoresis was more effective [the apparent permeability coefficient was (1.2 +/- 0.4) x 10(-4) cm x h(-1)] than that of cathodal iontophoresis [(4.3 +/- 1.4) x 10(-5) cm x h(-1)]. The amount of permeated defibrase caused by anodal iontophoresis in pH 7.4 medium was (25 +/- 5) x 10(-14) mol x cm(-2), which was higher than that of in pH 6. 4 permeation medium [(15 +/- 4) x 10(-14) mol x cm(-2)].
Iontophoresis could enhance skin permeation of defibrase. Electroosmotic flow effect played an important role.
Yao xue xue bao = Acta pharmaceutica Sinica 03/2005; 40(2):178-81.
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ABSTRACT: There are many ongoing investigations to improve the oral bioavailability of peptide and protein formulations. Bioadhesive polysaccharide chitosan nanoparticles (CS-NPs) would seem to further enhance intestinal absorption of them. In this study, Insulin-loaded CS-NPs were prepared by ionotropic gelation of CS with tripolyphosphate anions. Its particle size distribution and zeta potential were determined by photon correction spectroscopy and laser Dopper anemometry. The ability of CS-NPs to enhance intestinal absorption of insulin and increase the relative pharmacological bioavailability of insulin was investigated by monitoring the plasma glucose level of alloxan-induced diabetic rats after oral administration of various doses of insulin-loaded CS-NPs. CS-NPs had a particle size in the range of 250-400 nm and its polydispersity index was smaller than 0.1, positively charged, stable. Insulin association was found up to 80% and its in vitro release showed a great initial burst with a pH-sensitivity property. CS-NPs enhanced the intestinal absorption of insulin to a greater extent than the aqueous solution of CS in vivo. Above all, after administration of 21 I.U./kg insulin in the CS-NPs, the hypoglycemia was prolonged over 15 h and the average pharmacological bioavailability relative to SC injection of insulin solution was up to 14.9%.
International Journal of Pharmaceutics 01/2003; 249(1-2):139-47. · 3.35 Impact Factor
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ABSTRACT: To formulate and characterize insulin-loaded adhesive microspheres (MP) and evaluate drug effects of MP with various sizes, 120, 350, and 1000 nm in diameter, in the alloxan-induced diabetic rats.
Insulin-loaded MP were formulated by an ionotropic gelation procedure. Particle size distributions were determined by photon correlation spectroscopy and optical microscopy. The factors that influenced the particle sizes and loading capacity were investigated, and the release properties were assessed in vitro. The hypoglycemic effect was investigated by monitoring the plasma glucose level of the alloxan-induced diabetic rats after oral administration.
All the MPs with three sizes formulated were in the desired size range, and the loading capacity was 15.3 %+/-1.7 % (120 nm), 32.4 %+/-2.4 % (350 nm), and 53.3 %+/-2.7 % (1000 nm) respectively. The particle size also had an influence on the release property of the MPs. Half an hour later, 25 %+/-4 % (120 nm), 18.3 %+/-2.4 % (350 nm), and 8.6 %+/-1.3 % (1000 nm) of insulin were released. MP with different sizes had various degree of hypoglycemic effects after 10 h (P<0.05 vs control insulin solution). The plasma glucose level of 350 nm size particles remarkably decreased 15 h later (P<0.05 vs 120 nm) or 35 h later (P<0.01 vs others). The relative pharmacological availability was 10.2 %+/-0.5 % (120 nm), 14.9 %+/-1.3 % (350 nm), and 7.3 %+/-0.8 % (1000 nm) respectively. Particles of 350 nm showed a comparatively higher availability (P<0.05).
Adhesive CS-MP were helpful in increasing the relative pharmacological bioavailability of insulin, and a distinct advantage of proper particle size helped to increase the drug effects.
Acta Pharmacologica Sinica 12/2002; 23(11):1051-6. · 1.95 Impact Factor
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ABSTRACT: To study the enhancing effect of electroporation and iontophoresis on the permeation of insulin through human cadaver skin in vitro.
Using side by side two-chamber diffusion cells, the flux of insulin achieved with iontophoresis and electrophoration were compared.
The application of high-voltage pulse combined with iontophoresis resulted in higher flux transdermal permeation of insulin than either one technique alone (P < 0.05). Pulsing at a higher voltage increased the flux of insulin more dramatically than pulsing at a lower voltage (P < 0.01). The transdermal transport of insulin by 90 pulse of 500 V (exponential pulse generater, pulse time: 20-24 ms, pulse frequency: 3 pulse.min-1) followed by iontophoresis led to a quick input and a high steady flux.
Electroporation combined with iontophoresis can enhance the permeation of insulin significantly.
Yao xue xue bao = Acta pharmaceutica Sinica 08/2002; 37(8):649-52.
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ABSTRACT: To investigate the possibility of poly(lactic-co-glycolic acid) as a carrier for the delivery of macromolecular.
Insulin-loaded poly (lactic-co-glycolic acid) nanoparticles (INS-PLGA-NPs) was prepared by a double-emulsion solvent evaporation method. The size distribution was examined by photo-correlation spectrometry. The entrapment efficiency was determined by HPLC and important factors that affected the entrapment efficiency were investigated. The loading mechanism of different size nanoparticles was assayed by radioimmunoassay (RIA). INS-PLGA-NPs release behavior in vitro was carried out under sink condition. After oral administration of the nanoparticles to alloxan-induced diabetic rats, its glucose level was determined by glucose oxidize method and the oral pharmacological bioavailability in contrast to s.c. of insulin solution was calculated according to the area over the curve.
The INS-PLGA-NPs was prepared with poloxamer 188 as a emulsifier, the mean diameter was 149.6 nm and the polydispersity index was decreased to 0.09. While the entrapment efficiency was increased to 42.8%. Most of the insulin loaded was adsorbed on the surface of the nanoparticles. The release behavior in vitro showed an initial burst effect followed by a slower rate stage. After oral administration of 10 u.kg-1 INS-PLGA-NPs, the plasma glucose level decreased significantly after 4 h (P < 0.05), 10 h later the glucose level decreased to the lowest (52.4% +/- 10.2%, P < 0.01) and the relative pharmacological bioavailability is (10.3 +/- 0.8)%.
PLGA-NPs might be used as a new oral carrier for protein drug delivery systems in the future.
Yao xue xue bao = Acta pharmaceutica Sinica 06/2002; 37(5):374-7.
