ABSTRACT
Objective:To evaluate the effects of different doses of ulinastatin on lung function in patients undergoing total aortic arch replacement.Methods:One hundred and thirty five patients with acute Stanford type A aortic dissection of both sexes, aged 20-70 yr, with body mass index of 16.2-33.3 kg/m 2, of American Society of Anesthesiologist physical status Ⅳ, were divided into 3 groups ( n=45 each) using a random number table method: high-dose ulinastatin group (group H with total dose of 30 000 U/kg), low-dose ulinastatin group (group L with total dose of 20 000 U/kg) and control group (group C). In group H and group L, half of the total dose of ulinastatin was given after induction of anesthesia, the rest of the total dose was primed after being added to cardiopulmonary bypass (CPB) circuit, while normal saline 100 ml was given at the same time point in group C. After induction of anesthesia (T 0), and at 3, 6, 12, 24 and 48 h after the beginning of CPB (T 1-5), blood samples from the central vein were collected for determination of plasma concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The oxygenation index (OI) and alveolar-arterial partial pressure of oxygen difference (P A-aO 2) at T 0 and T 2-T 5, intraoperative blood loss and blood transfusion, postoperative mechanical ventilation time, length of intensive care unit (ICU) stay and the incidence of complications within 30 days after surgery were collected. Results:Compared with group C, the plasma concentrations of TNF-α and IL-6 were significantly at T 1-T 5, OI was increased, and P A-aO 2 was decreased at T 2, 3 in H and L groups ( P<0.05). There was no significant difference in the mechanical ventilation time, length of ICU stay and incidence of complications within 30 days after surgery among the 3 groups ( P>0.05). Conclusion:Ulinastatin can inhibit inflammatory responses and improve lung function in patients undergoing total aortic arch replacement, but it has no value for clinical outcomes.
ABSTRACT
Objective:To evaluate the effect of ulinastatin on hyperoxia-induced acute lung injury (ALI) and its relationship with Wnt/β-catenin signaling pathway in infantile rats.Methods:A total of 36 clean-grade Sprague-Dawley rats, aged 14 days, weighing 40-50 g, were divided into 3 groups ( n=12 each): control group (C group), hyperoxia-induced ALI group (ALI group) and ulinastatin group (UTI group). Hyperoxia-induced ALI was induced by inhaling oxygen at concentration greater than 90% for 72 h. At 1 day after the model was established successfully, ulinastatin 50 000 U/kg was injected intraperitoneally daily at the same time for 3 consecutive days in group UTI, while the equal volume of normal saline was injected intraperitoneally at the same time point in C and ALI groups.The animals were sacrificed at 4 days after the model was established successfully, the lung tissues were taken for determination of the wet/dry weight ratio (W/D ratio), for microscopic examination of the pathological changes which were scored, for measurement of interleukin-6 (IL-6) IL-1β and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay) and for detection of the expression of phosphorylated glycogen synthase kinase (p-GSK-3β), Wnt3a and β-catenin by Western blot, and ultrastructure was examined with with an electron microscope. Results:Compared with C group, W/D ratio and lung injury score were significantly increased, the contents of IL-6, IL-1β and TNF-α were increased, and the expression of p-GSK-3β, Wnt3a and β-catenin were up-regulated in lung tissues in group ALI ( P<0.05). Compared with group ALI, W/D ratio and lung injury score were significantly decreased, the contents of IL-6, IL-1β and TNF-α were decreased, and the expression of p-GSK-3β, Wnt3a and β-catenin were down-regulated in lung tissues in group UTI ( P<0.05). The ultrastructure injury in group UTI was reduced as compared with group ALI. Conclusion:The mechanism by which ulinastatin can alleviate hyperoxia-induced ALI is related to inhibiting the activation of Wnt/β-catenin signaling pathway and decreasing inflammatory response in infantile rats.
ABSTRACT
Objective To evaluate the effect of ulinastatin on programmed necrosis in hippocampal neurons in a rat model of global cerebral ischemia-reperfusion (I/R).Methods Forty-eight clean-grade healthy adult male Sprague-Dawley rats,aged 8 weeks,weighing 280-320 g,were divided into 3 groups (n=16 each) using a random number table method:sham operation group (Sham group),global cerebral I/R group (I/R group) and ulinastatin group (UT group).Global cerebral I/R was produced by 4-vessel occlusion method in chloral hydrate-anesthetized rats in I/R and UT groups.Ulinastatin 100 000 U/kg was injected via the tail vein at the onset of ischemia in group UT,and the equal volume of normal saline was given instead in Sham and I/R groups.Neurological deficit score (NDS) was estimated at 6,12 and 24 h of reperfusion.Animals were sacrificed at 24 h of reperfusion,brains were removed and the hippocampi were obtained for examination of pathological changes (with a light microscope) and for determination of the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity (by spectrophotometry),and expression of receptor-interacting protein kinase 1 (RIPK1),RIPK3,and mixed lineage kinase domain-like protein (MLKL) in hippocampal tissues (by Western blot).Results Compared with Sham group,the NDS was significantly increased at each time point,the MDA content was increased,the SOD activity was decreased,and the expression of RIPK1,RIPK3 and MLKL was up-regulated in I/R and UT groups (P＜ 0.05).Compared with I/R group,the NDS was significantly decreased at each time point,the MDA content was decreased,the SOD activity was increased,and the expression of RIPK1,RIPK3 and MLKL was down-regulated in UT group (P＜0.05).The pathological changes of hippocampi were significantly attenuated in UT group when compared with I/R group.Conclusion The mechanism by which ulinastatin ameliorates global cerebral I/R injury is related to inhibiting programmed necrosis in hippocampal neurons of rats.
ABSTRACT
Five Zea mays cultivars (BRS Caatingueiro, BRS Gorutuba, BRS Sertanejo, BRS Asa Branca and BR 106) were evaluated considering their effect on the nutrition of the maize weevil Sitophilus zeamais, by analysis of total protein in adult fed with these cultivars and for the presence of lectins and trypsin inhibitors in grains. In addition, free-choice and no-choice assays were performed to investigate the resistance of grains of the Z. mays cultivars to an attack by S. zeamais. The BR 106 cultivar showed the lowest susceptibility index, followed by BRS Caatingueiro, BRS Asa Branca, BRS Sertanejo and BRS Gorutuba. The number of emerged adults in the Z. mays cultivars ranged from 213.17 to 74.0, and the lowest number of insects was recorded for the BR 106 cultivar. The insects were able to feed on grains of all cultivars, but the BR 106 cultivar showed the least reduction in dried biomass. Lectins were detected in extracts from BR 106, BRS Asa Branca, BRS Sertanejo and BRS Gorutuba, and the highest activity was shown by BR 106. The lowest protein assimilation was detected in the insects from treatments with BRS Asa Branca. The extracts from all cultivars were able to inhibit the activity of bovine trypsin, but this effect was not related to the resistance degree of Z. mays cultivars. The results suggest the resistance of BR 160 to the attack of S. zeamais, as well as indicating that the presence of lectin in the grains is the cause of this resistance.(AU)
Foram avaliadas cinco cultivares de Zea mays (BRS Caatingueiro, BRS Gorutuba, BRS Sertanejo, BRS Asa Branca e BR 106) e seu efeito na nutrição do gorgulho-do-milho Sitophilus zeamais, por meio da análise de proteína total em adultos alimentados com esses cultivares e a presença de lectinas e inibidores da tripsina nos grãos. Além disso, foram realizados ensaios com e sem chance de escolha para investigar a resistência dos cultivares de Z. mays ao ataque de S. zeamais. O cultivar BR 106 apresentou o menor índice de susceptibilidade, seguido por BRS Caatingueiro, BRS Asa Branca, BRS Sertanejo e BRS Gorutuba. O número de adultos emergidos nos cultivares de Z. mays variou de 213,17 a 74,0, e o menor número de insetos foi registrado para o cultivar BR 106. Os insetos foram capazes de se alimentar de todos os cultivares, no entanto, o BR 106 mostrou a menor redução na biomassa seca. As lectinas foram detectadas em extratos de BR 106, BRS Asa Branca, BRS Sertanejo e BRS Gorutuba, e a maior atividade foi demonstrada pela BR 106. A menor assimilação de proteína foi detectada nos insetos que se alimentaram com BRS Asa Branca. Os extratos de todos os cultivares foram capazes de inibir a atividade da tripsina bovina, mas esse efeito não está correlacionado ao grau de resistência dos cultivares de Z. mays. Os resultados sugerem a resistência da BR 160 ao ataque de S. zeamais, além de indicar que a presença de lectina nos grãos é a causa dessa resistência.(AU)
Subject(s)
Zea mays , Weevils , Coleoptera , Insecta , LectinsABSTRACT
Objective To investigate the effects of ulinastatin preconditioning combined with postconditioning on kidney injury of pediatric patients undergoing living donor liver transplantation (LDLT) and the underlying mechanism.Methods Forty pediatric patients with biliary atresia,scheduled for LDLT,were randomly divided into two groups (n =20 each):the ulinastatin group and the control group using a random number table.Ulinastatin (20 000 U/kg) was diluted into 10 000 U/mL with normal saline,and it was then injected intravenously in 2 parts (1/2 was given before skin incision;1/2 at 5 min before portal vein declamping) in the ulinastatin group.In the control group,the equal volume of normal saline was given instead of ulinastatin.Blood samples and urine specimens were taken from the central vein immediately before skin incision (T0,baseline),at 30 min of anhepatic period (T1),at 1 h of neohepatic period (T2),at the end of surgery (T3),and 24 h after surgery (T4) for the determination.The concentrations of serum and urine β2-microglobulin (β2-MG) were measured using an immunonephelometric method.The levels of serum TNF-α,IL-6 and IL-18 were measured using an ELISA method.The serum concentrations of creatinine (Cr) and blood urea nitrogen (BUN) were measured using a colorimetry method.Results The serum Cr,BUN,β2-MG and urine β2-MG concentrations were higher at T2-4 than at T0 in the two groups (P＜0.05 or 0.01).As compared with the control group,the serum Cr,BUN,β2-MG and urine β2-MG concentrations were significantly decreased in the ulinastatin group (P＜0.05 or 0.01).The serum levels of TNF-α,IL-6 and IL-18 were higher at T2 4 than at T0 in the two groups (P＜0.05 or 0.01).As compared with the control group,the serum levels of TNF-α,IL-6,and IL-18 were significantly decreased in the ulinastatin group (P＜0.05 or 0.01).Conclusion Ulinastatin preconditioning combined with postconditioning can alleviate kidney injury in pediatric patients undergoing LDLT to some extent,which may be related to inhibiting the excessive release of inflammatory factors.
ABSTRACT
Objective To evaluate the effect of ulinastatin on the activity of Janus kinase 2/signaling transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway during focal cerebral ischemia-reperfusion (I/R) in rats.Methods Forty-eight clean-grade healthy adult male Sprague-Dawley rats,aged 6-8 weeks,weighing 230-280 g,were divided into 3 groups (n=16 each) using a random number table:sham operation group (S group),cerebral I/R group (I/R group) and ulinastatin group (U group).Focal cerebral I/R was induced by occlusion of the middle cerebral artery for 2 h followed by reperfusion.Ulinastatin 100 000 U/kg was injected via the femoral vein immediately after beginning of cerebral ischemia in group U.Neurologic deficit was evaluated and scored (NDS) at 24 h of reperfusion.The rats were then sacrificed and brains were removed for measurement of the cerebral infarct size (by TTC staining) and for determination of the expression of total JAK2,total STAT3 and phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) in the cerebral cortex.Results Compared with S group,NDS and cerebral infarct size were significantly increased,and the expression of p-STAT3 and p-JAK2 in the cerebral cortex was up-regulated in I/R group and U group (P＜0.05).Compared with I/R group,NDS and cerebral infarct size were significantly decreased,and the expression of p-STAT3 and p-JAK2 in the cerebral cortex was down-regulated in U group (P＜0.05).There was no significant difference in the expression of total JAK2 and total STAT3 in the cerebral cortex between three groups (P＞0.05).Conclusion Ulinastatin can inhibit the activity of JAK2/STAT3 signaling pathway during cerebral I/R,which may be involved in the brain protective mechanism of ulinastatin in rats.
ABSTRACT
Objective To evaluate the effect of ulinastatin on postoperative cognitive dysfunction in preoperative sleep deprived aged rats.Methods Sixty clean healthy male Sprague-Dawley rats,aged 18 months,weighing 350-500 g,were divided into 3 groups (n=20 each) using a random number table:control group (group C),sleep deprivation group (group D) and ulinastatin group (group U).Sleep deprivation was induced by using modified multiple platform method in D and U groups,and then splenectomy was performed in three groups.Ulinastatin 100 U/g was intraperitoneally injected before sleep deprivation and immediately after operation in group U.Ten rats were randomly selected at 3 days after operation and sacrificed,and hippocampi were removed for determination of the contents of interleukin-1β (IL-1β),IL-6 and tumor necrosis factor-α (TNF-α) by enzyme-linked immunosorbent assay.Morris water maze test was performed at 3-7 days after operation in the rest ten rats in each group,and the escape latency and time of staying at the original platform were recorded.Results Compared with group C,the escape latency was significantly prolonged at 4-6 days after operation,the time of staying at the original platform was shortened,and the contents of IL-1β,IL-6 and TNF-α were increased at 3 days after operation in D and U groups (P＜0.05).Compared with group D,the escape latency was significantly shortened at 4-6 days after operation,the time spent in the original platform was prolonged,and the contents of IL-1β,IL-6 and TNF-α were decreased at 3 days after operation in group U (P＜0.05).Conclusion Ulinastatin can mitigate postoperative cognitive dysfunction in preoperative sleep deprived aged rats,which is related to inhibiting inflammatory responses.
ABSTRACT
Objective To evaluate the effect of ulinastatin (UT1) on the expression of aquaporin 1 (AQP1) and AQP5 in rats with acute lung injury induced by cardiopulmonary bypass (CPB).Methods Forty-eight clean-grade healthy adult male Sprague-Dawley rats,weighing 200-250 g,were divided into 3 groups (n=16 each) using a random number table method:sham operation group (Sham group),CPB group and UTI group.UTI 200 000 U/kg was injected intravenously at 10 min prior to CPB in UTI group.The model of CPB was established in CPB and UTI groups.The equal volume of normal saline was intravenously injected at 10 min prior to puncture or at 10 min prior to CPB in Sham and CPB groups.Rats were sacrificed,and lung tissues were excised for determination of weight to dry weight ratio (W/D ratio),expression of AQP1 and AQP5 (by immunohistochemistry),expression of AQP1 and AQP5 protein and mRNA (by real-time polymerase chain reaction or Western blot) and for examination of morphological structure (with a light microscope) and ultrastructure of lung tissues (with an electron microscope).Injured alveolar rate (IAR) and rates of AQP1 and AQP5 positive cells were calculated.Results Compared with Sham group,W/D ratio and IAR were significantly increased,rates of AQP1 and AQP5 positive ceils were decreased,and the expression of AQP1 and AQP5 protein and mRNA was down-regulated in CPB and UTI groups (P＜0.05).Compared with CPB group,W/D ratio and IAR were significantly decreased,rates of AQP1 and AQP5 positive cells were increased,and the expression of AQP1 and AQP5 protein and mRNA was up-regulated in UTI group (P＜0.05).The injury to morphological structure and ultrastructure was significantly attenuated in UTI group when compared with CPB group.Conclusion The mechanism by which UTI pretreatment reduces CPB-induced acute lung injury is related to up-regulating the expression of AQP1 and AQP5 in rats.
ABSTRACT
Objective To evaluate the effect of ulinastatin on neuronal apoptosis in spinal cord af-ter peripheral nerve injury in mice. Methods A total of 225 healthy male SPF C57BL∕6J mice, aged 6-8 weeks, weighing 18-22 g, were divided into 3 groups ( n=75 each) using a random number table method:sham operation group ( group Sham), peripheral nerve injury group ( group PNI) and ulinastatin group ( group UTI) . The model of unilateral sciatic nerve transection was established in PNI and UTI groups. Uli-nastatin 10000 U∕kg was injected intraperitoneally once a day for 3 consecutive days in group UTI, while the equal volume of normal saline was given instead in Sham and PNI groups. The mice were sacrificed at 1, 3, 7, 14 and 28 days after administration ( T0-4 ) , and the L4-6 segments of the spinal cord were re-moved for examination of the pathological changes ( under the light microscope ) and for determination of neuronal apoptosis (by TUNEL) and expression of caspase-12, Bcl-2, Bax and activated caspase-3 (by Western blot) and expression of caspase-12 mRNA ( by real-time polymerase chain reaction) . Apoptosis in-dex ( AI) and Bcl-2∕Bax ratio were calculated. Results Compared with group Sham, AI was significantly increased, the expression of Bcl-2 was down-regulated, the expression of caspase-12, activated caspase-3 and Bax was up-regulated, and Bcl-2∕Bax ratio was decreased in PNI and UTI groups (P<0. 05). Com-pared with group PNI, AI was significantly decreased, the expression of Bcl-2 was up-regulated, the ex-pression of caspase-12, activated caspase-3 and Bax was down-regulated, and Bcl-2∕Bax ratio was in-creased in group UTI ( P<0. 05) . The pathological changes of the spinal cord were significantly attenuatedin group UTI than in group PNI. Conclusion Ulinastatin can inhibit neuronal apoptosis in the spinal cord after peripheral nerve injury in mice.
ABSTRACT
Objective To evaluate the effect of ulinastatin on postoperative outcomes in elderly patients undergoing thoracoscopic radical operation for lung cancer.Methods Sixty patients of both sexes,aged 65-80 yr,weighing 40-85 kg,of American Society Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for thoracoscopic radical operation for lung cancer,were divided into 2 groups (n =30 each) using a random number table method:ulinastatin group (group UTI) and normal saline group (group NS).Ulinastatin 0.5× 104 U/kg was intravenously infused within 1 h before skin incision in group UTI,while the equal volume of normal saline was given instead in group NS.Central venous blood samples were collected at 30 min before skin incision (T0),30 min after start of surgery (T1),and 1 h and 1,3 and 5 days after surgery (T2-5) for determination of the expression of CD42a+,HLADR+ and CD14+ in monocytes (using the flow cytometry),plasma concentrations of interleukin-6 (IL-6),IL-8 and tumor necrosis factoralpha (TNF-α) (by enzyme-linked immunosorbent assay),and the plasma C-reactive protein (CRP) concentration (by immunoturbidimetry).The ratios of monocyte-platelet adhesion (CD42a+/CD14+) and monocyte activation function (HLADR+/CD14+) were calculated.Cognitive function was assessed and scored on day 1 before operation and day 7 after operation,and the incidence of postoperative cognitive dysfunction (POCD) was calculated using Z score.Results Compared with group NS,the CD42a+/CD14+ ratio was significantly decreased at T1-3,the HLADR+/CD14+ ratio was increased at T3,4,the concentrations of plasma IL-6,IL-8,TNF-α and CRP were decreased at T1-5,and the incidence of POCD was decreased in group UTI (P＜0.05).Compared with the baseline value at T0,the HLADR+/CD14+ ratio was significantly decreased at T2-4 in group UTI,the HLADR+/CD14+ ratio was decreased at T2-5,and the CD42a+/CD14+ ratio was increased at T1,2 and T4,5 in group NS,and the concentrations of plasma IL-6,IL-8,TNF-α and CRP were increased at T1-5 in the two groups (P＜0.05).Conclusion Ulinastatin can promote postoperative outcomes in the elderly patients undergoing thoracoscopic radical operation for lung cancer.
ABSTRACT
Este estudio se realizó para determinar la composición química e indicadores de calidad del frijol de soya (Glycine max) integral (FSI) procesado con vapor en un autoclave bajo condiciones estándares de trabajo a 2,30 bar de presión a 103°C/30 min. Se tomaron seis muestras después del procesamiento de cada uno de tres lotes de soya provenientes de Estados Unidos. Se obtuvo la media por lote y general para cada variable con el error estándar (± EE). Las medias generales de materia seca, proteína, grasa, fibra, ceniza, Ca y P (g/100 g) y energía bruta (kcal/kg) fueron 91,40±0,40; 36,82±0,18; 20,88±0,49; 6,69±0,21; 4,80±0,05; 0,30±0,06; 0,53±0,006 y 5732±44,14, respectivamente. Hubo variaciones entre lotes para materia seca, P (P<0,01), fibra, ceniza y energía bruta (P≤0,05). Se observó predominio de lisina, arginina y leucina cuyas medias generales fueron 2,26±0,01; 2,70±0,01 y 2,81±0,01, respectivamente. Los ácidos grasos predominantes fueron oleico y linoleico con medias generales (g/100g) de 21,65±0,12 y 51,07±0,13, respectivamente. Se observaron variaciones (P≤0,01) entre lotes en la acidez y en los índices de saponificación, yodo y acidez. Las medias generales para inhibidores de tripsina, solubilidad de la proteína en KOH, actividad de ureasa y lisina reactiva fueron 3,04 ± 0,36 mg/g de muestra; 80,29 ± 1,09%; 0,05 ± 0,01% y 1,87±0,06%, respectivamente. Aunque hubo variaciones entre lotes para algunos componentes e indicadores de calidad, el FSI procesado con vapor es una fuente proteica de buena calidad, con buen contenido de lisina, grasa, energía bruta y ácidos grasos esenciales para la alimentación de aves y cerdos(AU)
This study was conducted to determine the chemical composition and quality indicators of full-fat soybean (Glycine max) (FFSB) steam processed in an autoclave under standard contitions of work of 2.30 bar of pressure and 103°C/30 min. Six samples were taken after the processing of each of three soybean batches from the United States. The average was obtained by batch and overall for each variable with the standard error of the mean (± SEM). The total averages of dry matter, protein, fat, fiber, ash, Ca and P (g/100g) and gross energy (kcal/kg) were 91.40±0.40, 36.82 ± 0.18; 20.88±0.49, 6.69 ± 0.21, 4.80±0,05, 0.30±0.06, 0.53±0.006, and 5732±44.14, respectively. There were variations among batches for dry matter, P (P<0.01), fiber, ash and gross energy (P≤0.05). There was a predominance of lysine, arginine and leucine (g/100 g) with average of 2.26±0.01, 2.70±0.01 and 2.81±0.01, respectively. The predominant fatty acids (g/100 g) were oleic and linoleic with general averages of 21.65 ± 0.12 and 51.07 ± 0.13, respectively. There were variations (P≤0.01) among batches in acidity and saponification, iodine and acidity index. The average for trypsin inhibitors, protein solubility in KOH, urease activity and reactive lysine were 3.04 ± 0.36 mg/g of sample; 80.29 ± 1.09%, 0.05 ± 0.01% y 1.87±0.06%, respectively. Although there were variations among batches for some components and quaility indicators, the FFSB steam processed is a protein source of good quality with good content of lysine, fat, gross energy and essential fatty acids for feeding poultry and swine(AU)
Subject(s)
Food Composition , Food Technology , Fabaceae , Whole Foods , Amino Acids, Peptides, and ProteinsABSTRACT
Objective To evaluate the effect of ulinastatin pretreatment on endoplasmic reticulum stress during myocardial injury in the patients undergoing mitral valve replacement (MVR) with cardiopulmonary bypass (CPB).Methods One hundred patients of both sexes,aged 35-64 yr,weighing 40-80 kg,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ (New York Heart Association Ⅱ or Ⅲ),scheduled for elective MVR with CPB,were divided into ulinastatin pretreatment group (UP group,n=50) and normal saline control group (NS group,n =50) using a random number table.Ulinastatin 0.5× 104 U/kg was intravenously infused over 1 h before skin incision,and administration was repeated every 4 h until the end of operation in group UP,while the equal volume of normal saline was given instead in group NS.Immediately after opening the right atrium (T0),at 30 min after aortic clamping (T1) and while suturing the right atrium (T2),blood samples were collected from the radial artery for measurement of the concentrations of plasma creatine kinase-MB and cardiac troponin T by enzyme-linked immunosorbent assay.Right auricle specimens were obtained after blood sampling at each time point for determination of the expression of glucose-regulated protein 78,CCAAT/enhancer-binding protein homologous protein and c-Jun N-terminal kinase protein and mRNA (by real-time polymerase chain reaction and Western blot,respectively) and apoptosis in cardiomyocytes (by TUNEL).The apoptosis rate was calculated.Results Compared with group NS,the plasma concentrations of creatine kinase-MB and cardiac troponin T at T1 and T2 and apoptosis rate at T2 were significantly decreased,and the expression of glucose-regulated protein 78,CCAAT/enhancer-binding protein homologous protein and c-Jun N-terminal kinase protein and mRNA was down-regulated at T1 and T2 in group UP (P＜0.05).Conclusion The mechanism by which ulinastatin pretreatment inhibits apoptosis in cardiomyocytes and attenuates myocardial injury is related to decrease in endoplasmic reticulum stress in the patients undergoing MVR with CPB.
ABSTRACT
Objective To evaluate the effect of ulinastatin on acute kidney injury in the pediatric patients undergoing living-donor liver transplantation (LDLT).Methods Forty pediatric patients with congenital biliary atresia,aged 5-14 months,weighing 5.5-10.0 kg,of American Society of Anesthesiologists physical status Ⅲ or Ⅳ,scheduled for elective LDLT,were divided into either control group (group C,n=20) or ulinastatin group (group U,n=20) using a random number table.Ulinastatin 20 000 U/kg was diluted to 10 000 U/ml in normal saline and then intravenously infused in 2 parts (1/2 was given immediately before skin incision;1/2 at 5 min before portal vein declamping) in group U.The equal volume of normal saline was given instead of ulinastatin at the same time points in group C.Immediately before skin incision (To,baseline),at 30 min of anhepatic period (T1),at 1 h of neohepatic period (T2),at the end of surgery (T3) and at 24 h after surgery (T4),blood samples from the central vein and urine specimens were collected for determination of creatinine (Cr) and blood urea nitrogen (BUN) concentrations in serum (by colorimetric assay) and β2-microglobulin (β2-MG) concentrations in serum and urine (using immunoturbidimetric method).The urine volume,requirement for dopamine and diuretics and occurrence of adverse cardiovascular events (hypotension,myocardial ischemia,ventricular premature beat)were recorded during surgery.The changing rates of Cr,BUN and β2-MG concentrations in serum and β2-MG concentrations in urine were calculated at T1-4.Results Compared with group C,the urine volume was significantly increased,Cr and β2-MG concentrations in serum,β2-MG concentrations in urine and the changing rates were decreased at T2-4,serum BUN concentrations and the changing rates were decreased at T3,4 (P＜0.05 or 0.01),and no significant changes were found in the incidence of adverse cardiovascular events or requirement for dopamine and diureitcs in group C (P＞0.05).Conclusion Ulinastatin can attenuate acute kidney injury in the pediatric patients undergoing LDLT.
ABSTRACT
Objective To evaluate the role of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in ulinastatin-induced reduction of oxidative stress injury to cardiomyocytes of rats.Methods H9c2 cells were inoculated in 96-well plates at a density of 104 cells/well.The cells were divided into 5 groups using a random nomber table:control group (group C,n =12),H2O2 group (n=12),H2O2 plus ulinastatin group (group HU,n=12),H2O2 plus ulinastatin plus LY294002 group (group HUL,n=9) and H2O2 plus LY294002 group (group HL,n=9).In group H2O2,H2O2 (final concentration 200 μ mol/L) was added,and the cells were incubated for 12 h in the incubator.In HU,HL and HUL groups,ulinastatin (final concentration 50 U/ml),LY294002 (final concentration 10 μmol/L),and ulinastatin (final concentration 50 U/ml) plus LY294002 (final concentration 10 μmol/L)were added,respectively,the cells were incubated for 2 h,H2O2 (final concentration 200 μmol/L) was then added,and the cells were incubated for 12 h in the incubator.The cell survival rate was measured by methyl thiazolyl tetrazolium assay.The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined by using water soluble tetrazolium-1 and thiobarbituric acid colorimetric assays.Cell apoptosis was measured by flow cytometry,and apoptosis rate (AR) was calculated.The expression of Akt,phosphorylated Akt (p-Akt),mTOR,phosphorylated mTOR (p-mTOR),activated caspase-3 and activated poty-ADP-ribose polymerase (PARP) was detected by Western blot.The p-Akt/AKT and pmTOR/mTOR ratios were calculated.Results Compared with group C,the cell survival rate was significantly decreased,AR was increased,the SOD activity was decreased,the MDA content was increased,the expression of activated caspase-3 and PARP was up-regulated (P＜0.05),and no significant change was found in p-Akt/AKT ratio or p-mTOR/mTOR ratio in group H2O2 (P＞0.05).Compared with group H2O2,the cell survival rate was significantly increased,AR was decreased,the SOD activity was increased,the MDA content was decreased,the p-Akt/AKT and p-mTOR/oTOR ratios were increased,and the expression of activated caspase-3 and PARP was down-regulated in group HU (P＜0.05).Compared with group HU,the cell survival rate was significantly decreased,AR was increased,and the expression of activated caspase-3 and PARP was up-regulated in group HUL (P＜0.05).Conclusion The mechanism by which ulinastatin reduces oxidative stress injury to cardiomyocytes is related to activation of Akt/mTOR signaling pathway in rats.
ABSTRACT
Objective To evaluate the effect of ulinastatin on endoplasmic reticulum stress in car-diomyocytes of patients undergoing beating heart mitral valve replacement(MVR). Methods A total of 80 patients of both sexes with rheumatic heart disease complicated with mitral valve stenosis, aged 38-59 yr, weighing 43-73 kg, with American Society of Anesthesiology physical statusⅡorⅢ, scheduled for elective MVR, were divided into ulinastatin group(UTI group, n=40)and normal saline group(NS group, n=40) using a random number table. Immediately after opening the right atrium(T0), at 30 min of cardiopulmonary bypass(T1)and while suturing the right atrium(T2), blood samples from the radial artery were collected to determine the concentrations of plasma creatine kinase-MB and cardiac troponin T by enzyme-linked immu-nosorbent assay, and the right auricle specimens were collected for determination of the expression of glucose-regulated protein 78, CCAAT∕enhancer-binding protein homologous protein, c-Jun amino-terminal kinase (JNK)protein and mRNA(by real-time polymerase chain reaction or Western blot)and phosphorylated JNK (p-JNK)expression(by Western blot). The apoptosis in cardiomyocytes was detected by TUNEL at T0,2, and the apoptosis rate was calculated. Results Compared with group NS, the concentrations of plasma crea-tine kinase-MB and cardiac troponin T at T1,2and the apoptosis rate of cardiomyocytes were significantly de-creased at T2, and the expression of glucose-regulated protein 78, CCAAT∕enhancer-binding protein homolo-gous protein and JNK protein and mRNA and p-JNK was down-regulated at T1,2in group UTI(P<0.05). Conclusion The mechanism by which ulinastatin reduces myocardial damage is related to inhibiting endo-plasmic reticulum stress in cardiomyocytes of patients undergoing beating heart MVR.
ABSTRACT
Objective To evaluate the effect of ulinastatin on hepatic ischemia-reperfusion injury in patients with hepatic alveolar echinococcosis in plateau region.Methods Sixty patients with hepatic alveolar echinococcosis in plateau region,weighing 45-75 kg,aged 30-55 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective partial hepatectomy,were divided into control group (C group) and ulinastatin group (U group) using a random number table,with 30 patients in each group.Ulinastatin 12 000 U/kg (in 100 ml of normal saline) was infused intravenously at 20 min before occlusion of hepatic portal in group U,and normal saline 100 ml was given instead in group C.Before operation,at 10 min after occlusion of hepatic portal,at 20 min and 1 h after unclamping hepatic portal and at 12 h after operation,blood samples were collected from the right internal jugular vein for determination of the levels of serum alanine aminotransferase,aspartate aminotransferase and malondialdehyde.Results Compared with group C,the levels of serum alanine aminotransferase,aspartate aminotransferase and malondialdehyde were significantly decreased at 20 min and 1 h after unclamping hepatic portal and 12 h after operation in group U (P＜0.05).Conclusion Ulinastatin can attenuate hepatic ischemia-reperfusion injury in patients with hepatic alveolar echinococcosis in plateau region.
ABSTRACT
Objective To investigate the effect of ulinastatin on brain injury in the pediatric patients undergoing living-related liver transplantation (LRLT).Methods Sixty pediatric patients with congenital biliary atresia,of both sexes,aged 6-10 months,weighing 6.5-9.5 kg,of American Society of Anesthesiologists physical status Ⅲ or Ⅳ,scheduled for elective LRLT,were randomly divided into either control group (group C,n =30) or ulinastatin group (group U,n =30) using a random number table.Starting from the end of anesthesia induction to the end of surgery,ulinastatin 10 000 U/kg was infused intravenously in group U,while the equal volume of normal saline was infused intravenously in group C.Before operation,at 30 min of anhepatic phase,and at 3 and 24 h of neohepatic phase,blood samples were drawn from the central vein for determination of the concentrations of S-100β protein and neuron-specific enzyme in serum (by enzyme-linked immunosorbent assay) and concentrations of interleukin-6 (IL-6),IL-10 and IL-18 in serum (by radio-immunity method).Results Compared with group C,the serum concentrations of S-100β protein,neuron-specific enzyme,IL-6 and IL-18 were significantly decreased,and the serum concentration of IL-10 was significantly increased at 30 min of anhepatic phase and 3 and 24 h of neohepatic phase in group U (P＜0.05).Conclusion Ulinastatin 10 000 U/kg infused intravenously during operation can reduce brain injury in the pediatric patients undergoing LRLT.
ABSTRACT
Protein kinase C (PKC) is a group of phospholipid-dependent serine/threonine protein kinases, which togeth-er with protein kinase A (PKA) and protein kinase G (PKG) constitute a superfamily of serine/threonine protein kinase AGC. PKC includes classic PKC, novel PKC, atypical PKC and some members of kinase associated with PKC (PRK). PKC is wide-ly distributed in mammalian tissues and cells, which plays an important biological role in growth and metabolism, prolifera-tion and differentiation of cells. A series of studies have demonstrated that variations of multiple cells, occurrence and devel-opment of diseases are related to the abnormal expression of PKC. Therefore, designing and searching for efficient PKC inhib-itors have very important implications for synthesis of many kinds of effective drugs and treatment of a variety of clinical dis-eases including cancer, cardiovascular, and hypertension, et al. In recent years, the research on PKC inhibitors has become the focus of domestic and foreign research. A large number of literatures have reported many kinds of effective PKC inhibi-tors, and analyzed their function site, mechanism, clinical trial data and so on. The discovery of these PKC inhibitors has im-portant implications for structural analysis of PKC and the treatment of diseases. So in this paper, the efficient PKC inhibi-tors are summarized.
ABSTRACT
Objective To evaluate the effects of penehyclidine hydrochloride combined with ulinastatin on brain injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Forty-eight patients of both sexes,aged 20-64 yr,weighing 40-66 kg,of ASA physical status Ⅱ (NYHA Ⅱ),scheduled for elective cardiac valve replacement with CPB,were randomly divided into 4 groups (n =12 each) using a random number table:control group (group C),penehyclidine hydrochloride group (group P),ulinastatin group (group U),and penehyclidine hydrochloride and ulinastatin group (group PU).Penehyclidine hydrochloride 0.02 mg/kg was injected via the right internal jugular vein at 15 min before induction of anesthesia in group P.In group U,the total amount of ulinastatin was 2× 104 U/kg,30％ of the total amount was given via the right internal jugular vein after induction and before surgery,40％ was added to the priming solution,and the remaining 30％ was injected via the right internal jugular vein while the aorta was opened.In group PU,penehyclidine hydrochloride or ulinastatin was given according to the method previously described in group P or U.The equal volume of normal saline was given instead in group C.After induction and before surgery (T1),at 30 min of CPB (T2),and at 30 min and 6 h after termination of CPB (T3,4),blood samples were taken from the left internal jugular bulb and radial artery for blood gas analysis and determination of jugular venous oxygen saturation,jugular venous O2 content,arterial O2 content,and plasma concentrations of S-100β protein and neuron-specific enolase (NSE) (by ELISA).Arteriovenous oxygen content difference (Ca-jrO2) and cerebral O2 extraction rate (CERO2) were calculated.Results Compared with group C,SjvO2 was significantly increased,and CERO2 was decreased at T2.3 in P and U groups and at T2.4 in group PU,and Ca-jvO2 and plasma concentrations of S-100β protein and NSE were decreased at T2,3 in P,U and PU groups.The plasma concentrations of S-100β protein and NSE were significantly lower at T2,3 in group PU than in P and U groups.Conclusion The combination of penehyclidine hydrochloride and ulinastatin produces better efficacy than either alone in attenuating brain injury in patients undergoing cardiac valve replacement with CPB.
ABSTRACT
Objective To evaluate the effects of ulinastatin on hemorrhagic shock and resuscitation ( HS∕R)?induced acute lung injury in rats. Methods Fifteen SPF adult Sprague?Dawley rats, aged 2-3 months, weighing 300-400 g, were divided into 3 groups ( n=5 each) using a random number table:sham operation group ( group S ) , HS∕R group and ulinastatin group ( group U ) . Carotid arteries were cannulated for blood pressure monitoring and blood?letting. HS∕R was induced by blood?letting and maintained for 1 h, followed by resuscitation with autologous blood transfusion and infusion of normal saline. After cannulation of carotid arteries ( T0 ) , at 5 min after hemorrhagic shock ( T1 ) , before resuscitation ( T2 ) , at 5 min after the expected blood pressure was achieved following resuscitation ( T3 ) , and at 30 min, 1?5 h and 2?5 h after resuscitation ( T4?6 ) , arterial blood samples were collected for determination of interleukin?6 ( IL?6 ) and tumor necrosis factor?α ( TNF?α) concentrations ( by enzyme?linked immunosorbent assay) . Arterial blood samples were collected at T0 , T2 and T6 for blood gas analysis. The pH value, partial pressure of arterial carbon dioxide ( PaCO2 ) , HCO-3 and base excess ( BE) value were recorded, and oxygenation index ( PaO2∕FiO2 ) was calculated. Lungs were removed at T6 , and pulmonary specimens were obtained for examination of pathological changes which were scored, and nucleus was extracted for determination of nuclear factor?kappa B ( NF?κB ) p65 expression by enzyme?linked immunosorbent assay. Results Compared with group S, the pH values, HCO-3 , BE values and OI were significantly decreased, and PaCO2 , plasma IL?6 and TNF?α concentrations, expression of NF?κB p65 in lung tissues, and pathological scores were increased in U and HS∕R groups. Compared with group HS∕R, the plasma concentrations of IL?6 and TNF?α, expression of NF?κB p65 in lung tissues, and pathological scores were significantly decreased, and no significant changes were found in parameters of blood gas analysis in group U. Conclusion Although ulinastatin can alleviate HS∕R?induced acute lung injury, it is insufficient to improve lung oxygenation in rats.