Release of tumour necrosis factor alpha into bronchial alveolar lavage fluid following antigen challenge in passively sensitized guinea-pigs

Five groups of ten female guinea-pigs were passively sensitized against ovalbumin (OA) (n = 9) or control guinea-pig serum (n = 1). 24 h later, they received mepyramine (0.5 mg/kg, i.p.) and 30 min later inhaled aerosols of: (A) OA (2 in 0.9% saline, 8 min, n = 4/9); (B) saline (40 min, n = 4/9); (C) LPS (40 min, Escherichia coli 0111:B4, 150 ng/kg in PBS, n = 1/9); and (D) the control animal was treated as in (C) (n = 1). Their tracheas were cannulated under pentobarbital anaesthesia and bronchial alveolar lavage (BAL) was performed with 2 x 5 ml PBS containing BSA (1%) (n = 1 group), or BSA (1%) and aprotinin (1000 KIU/ml) (n = 4 groups), at 30, 60, 90 or 120 min post-inhalations. BAL fluids recovered were centrifuged, the supernatants recovered and frozen until assayed for tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6). No TNF-alpha could be detected unless aprotinin was present in the lavaging solution. BAL fluid from OA-sensitized and control animals that had inhaled LPS contained high levels of TNF-alpha that peaked at 90 min. BAL fluid from OA sensitized animals that inhaled OA aerosols contained no detectable TNF-alpha at 30 min, but it was found in increasing amounts at 60, 90 and 120 min; TNF-alpha was not detected in fluid from any of the animals that inhaled saline. As BAL fluids were toxic to the cells used in the assays, neither IL-1 nor IL-6 could be measured. We conclude that the monokine TNF-alpha is released into BAL fluid following anaphylactic challenge of passively sensitized guinea-pigs. The presence of the antiprotease, aprotinin, in the lavaging solution is essential for the detection and measurement of TNF-alpha in BAL fluid.     

Protective effects of intraperitoneal vitamin C, aprotinin and melatonin administration on retinal edema during experimental uveitis in the guinea pig

A considerable amount of clinical and experimental evidence exists suggesting the involvement of reactive oxygen substances (ROS) in the aetiology of uveitis. The activated phagocytic system of polymorphonuclear leucocytes in uveitis is involved in the generation of ROS. In addition to their direct free radical scavenging action, aprotinin, melatonin and vitamin C are known to protect against oedema formation and can preserve plasma membrane fluidity and free radical production. Histological changes in the retina that occur during uveitis are not well explained. The purpose of this study was to determine whether vitamin C, aprotinin and melatonin can protect the retina from damage accompanying experimental uveitis (EU). Thirty adult male guinea pigs were divided into five groups of six animals each. The first group was used as control. The right eyes of groups 2, 3, 4 and 5 received an intravitreal injection of bovine serum albumin for induction of experimental uveitis. At the same time and also on the consecutive third day, groups 3, 4 and 5 received intraperitoneal injections of vitamin C (ascorbic acid, 100 mg kg(-1) body wt), aprotinin (20,000 kIU kg(-1) body wt) and melatonin (10 mg kg(-1) body wt), respectively. The animals were killed on the sixth day. The average thickness of the retina and inner plexiform layer for each eye was measured in sagittal section near the optic nerve and expressed in microns. The thickness of the retina and inner plexiform layer in the control group was significantly (p < 0.01) lower than in the group EU as compared with the group EU plus vitamin C, group EU plus aprotinin, group EU plus melatonin (p < 0.05). The thicknesses of the retina and inner plexiform layer in group EU plus vitamin C, group EU plus aprotinin and group EU plus melatonin were significantly (p < 0.01) lower than that in the group EU. The difference in thickness of the retina and inner plexiform layer among the groups 3, 4 and 5 was not significant (p > 0.05). In conclusion, this study demonstrated that oedematous effects of EU on the retina were reduced by the administration of intraperitoneal vitamin C, aprotinin and melatonin, i.e. these antioxidants had significant protective effects on the retina of guinea pigs against oedematous damage in EU. However, the reductive effect of vitamin C on EU was greater than that of aprotinin and melatonin. The intraperitoneal vitamin C, aprotinin and melatonin supplementations may strengthen the antioxidant defence system because of decreased ROS, and these agents may play a role in treating uveitis.     

Aprotinin turn-over studies in dog and in man with severe acute pancreatitis

The elimination of aprotinin after intravenous infusion was exponential until 95% of the dose was cleared from the plasma after 1 h in dogs with bile-induced pancreatitis. The half-life of this part of the elimination was 10 min. The concentration of aprotinin in the peritoneal fluid reached a maximum plateau after 1 h. Direct intra-abdominal infusion of aprotinin was followed by a relatively slow elimination of the inhibitor from the cavity. One hour after the infusion the concentration of aprotinin in the peritoneal exudate was about 50% of the initial value. Four hours later the concentration of inhibitor with unchanged immunoreactivity and inhibiting capacity was still about 25% of the initial value. Based on the results of this experimental study an intraperitoneal dosage schedule for aprotinin was tested in three patients with haemorrhagic pancreatitis. A total amount of 14 X 10(6) KIU was given in repeated dosages during 18 h. This resulted in a minimum level of aprotinin in the peritoneal exudate of about 10 mumol/l. According to our earlier published data this level should largely block trypsin-induced effects relevant in pancreatitis. In conclusion; due to the rapid elimination of aprotinin from plasma, after i.v. application a therapeutically useful concentration is never reached in the peritoneum, while the elimination from the peritoneum is relatively slow, thus providing therapeutically useful concentrations which can be maintained for some time after i.p. application.     

Histochemical study of alkali-burned rabbit anterior eye segment in which severe lesions were prevented by aprotinin treatment

Activities of different enzymes (acid glycosidases, phosphatases, Na+ - K+ -dependent ATPase, proteases, dehydrogenases) and acid glycosaminoglycans were studied by histochemical methods in sections of rabbit anterior eye segments after experimental alkali burn and treatment with aprotinin, an inhibitor of plasmin and other serine proteinases. Solutions of sodium hydroxide (0.25-1.0 M) were applied on corneas using 12-mm-diameter plastic tube for 15-60 s. After wiping with cotton and rinsing with tap water aprotinin solutions were applied in saline (in experimental animals) and saline (in control animals) dropwise in 12-h intervals for a month. Within the first two weeks aprotinin was used at a concentration of 5000 IU/ml. During the subsequent two weeks the aprotinin concentration was reduced to 2500 IU/ml. Striking differences in enzyme activities and in the healing between treated and untreated eyes were found. Without aprotinin, ulcers developed in most corneas within 3 weeks and plasmin was regularly demonstrated in tears and in the aqueous. When aprotinin treatment was started within 24 h after the burn, the number of enzymatically active inflammatory cells was significantly lower, not only in the cornea itself but also in the whole anterior eye segment. With aprotinin treatment no ulcerations and no plasmin in tears and the aqueous were observed and the corneas healed within a month. The healing process started from the zone of enzymatically activated corneal cells in the unburned zone at the corneal periphery. In the regenerating epithelium and endothelium high activities of Na+ -K+ -dependent ATPase, gamma-glutamyltransferase, lactate and succinate dehydrogenases appeared very soon.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vitamin C Deficiency Facilitates 5-S-Cysteinyldopamine Formation in Guinea Pig Striatum

Being a catechol, dopamine (DA) is easily autoxidized in solution to a semiquinone and then further to a quinone. These quinones and by-products, as reduced forms of oxygen, are all cytotoxic. By quantifying quinone metabolites, such as 5-S-cysteinyl adducts of DA, 3,4-dihydroxyphenylalanine (DOPA), and 3,4-dihydroxyphenylacetic acid (DOPAC), an indirect measure of catechol autoxidation is available. Ascorbic acid (AA) has an important role as an antioxidant in the organism. A group of guinea pigs (Dunkin-Hartley) received an AA-free diet for 37 days, whereas a control group was fed an AA-containing diet (1,400 mg/kg of pellets). To one group of AA-deprived animals a single dose of AA (500 mg/kg, i.p.) was administered 2 h before death, whereas another group received two doses 9 and 24 h before death. The striatal levels of 5-S-cysteinyl adducts, DA, noradrenaline, and DOPAC and the cerebellar and the limbic levels of AA were determined. A significant increase in 5-S-cysteinyl-DA content was found in the striatum of AA-deficient animals (143 +/- 12% of control values). A further increase was found 2 h after an AA injection (177 +/- 16% of control values), which was significant compared with both controls and AA-deficient animals. An elevation in 5-S-cysteinyl-DA content was still observed following two AA injections during a 24-h period (153 +/- 7% of control values). The 5-S-cysteinyl-DOPAC content increased significantly (134 +/- 14% of control values) in the AA-deficient animals given AA acutely (2 h), both compared with controls and with the AA-deficient group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preservation of hepatic cell integrity by aprotinin in hypoxia

Perfused cat livers subjected to 2.5 hr of hypoxia exhibited dramatic increases in perfusate cathepsin D and lactic acid dehydrogenase (LDH) activities, amino nitrogen concentrations, and a 60% depression in the clearance rate of carbon particles by the reticuloendothelial system (RES). Addition of aprotinin (250 KIU/ml) to the perfusate prior to hypoxia prevented the increases in circulating cathepsin D, LDH, and amino-nitrogen observed at 150 minutes. In addition, aprotinin prevented the reduction in carbon clearance during severe hypoxia. However, aprotinin had no effect on the percent free cathepsin D activity indicating that this agent did not directly prevent increases in lysosomal fragility occurring in response to hypoxia. Thus, addition of pharmacologic doses of aprotinin to the perfusate protected RES cells, and markedly reduced the release of cytoplasmic and lysosomal enzymes. The prevention of cell membrane dissolution appears to be a critical factor in hepatic preservation, and may be related to the inhibition of proteolysis by aprotinin. These effects may help explain the therapeutic effectiveness of this agent in shock and in myocardial ischemia.     

Aprotinin reverses ECG abnormalities induced by Mesobuthus tamulus concanesis, Pocock venom in adult rats

The kinins are implicated in the pathogenesis of scorpion envenomation. Therefore, this study was carried out to examine the involvement of kinins for the ECG abnormalities induced by M. tamulus concanesis, (BT) venom in anaesthetized rats. ECG was recorded using needle electrodes with limb lead II configuration. The PR interval, QRS wave pattern, QRS duration, ST segment and heart rate were examined in saline only, venom alone, and venom after aprotinin groups. BT venom (5 mg/kg) produced heart block of varying degree and ischemia-like changes in ECG wave pattern and the animals died within 30 min after exposure to venom. In aprotinin pretreated animals, the initial ECG changes produced by venom persisted, but after 15 min the ECG pattern improved and the animals survived for the entire period of observation (120 min). The results indicate that aprotinin protected the rats against the cardiotoxicity induced by BT venom.     

Influence of plasma proteinase inhibitors and aprotinin on trypsin-induced bradykinin release in vitro in man

The consumption of kininogen (measured as kinin-releasable material) was studied in an experimental model in vitro. Analyses were made following the addition of increasing amounts of human cationic trypsin to human serum and plasma. The consumption of kininogen was correlated with the degree of saturation of the plasma proteinase inhibitors alpha 2-macroglobulin (alpha 2-M) and alpha 1-proteinase inhibitor (alpha 1-PI) with trypsin in the presence and absence of aprotinin (Trasylol). The level of kininogen fell dramatically when alpha 2-M was saturated to 70% in spite of 90% free alpha 1-PI. Trypsin-alpha 2-M complexes had no effect on kininogen levels. 60 mumol/l of aprotinin, i.e. approximately 3 X 10(6) KIU/l, blocked only 60% of the trypsin-induced kininogen consumption in serum, while 15 mumol/l of aprotinin blocked 100% of this consumption in plasma. With increasing concentration of aprotinin in serum, a decreasing consumption of alpha 2-M and especially of alpha 1-PI was observed on the addition of trypsin. The high aprotinin concentration needed to block trypsin-induced kininogen cleavage in human serum or plasma may explain the poor clinical effect of aprotinin to date in human acute pancreatitis.     

Immobilization of aprotinin to fibrinogen as a novel method for controlling degradation of fibrin gels

The goal of this work was to demonstrate that aprotinin conjugated to fibrinogen could (1) maintain its function and (2) control fibrin degradation. Using the chick chorioallantoic membrane (CAM) assay, we found that blood vessels did not directly invade fibrin constructs containing immobilized fibroblast growth factor-2. Because the fibrin quickly degraded within approximately 5 days, we hypothesized that controlling fibrinolysis may improve direct blood vessel invasion. Aprotinin, a protease inhibitor typically added to slow fibrinolysis, is a small protein and can diffuse out of the gel resulting in the loss of fibrinolysis protection. Therefore, using a novel synthesis strategy, aprotinin and a fluorescent reporter, Cy3, were chemically conjugated to fibrinogen. In vitro microplate absorbance assays showed that the conjugated aprotinin was able to inhibit plasmin-mediated fibrin degradation and that its activity was comparable to equimolar levels of soluble, nonconjugated aprotinin. Additionally, we found that fibrinolysis rates could be tuned by varying the level of conjugated aprotinin within the gel. The conjugated aprotinin also demonstrated functionality in vivo. In the chick CAM assay, fibrin gels containing conjugated aprotinin were approximately 5 times larger than gels containing soluble aprotinin after 4 days. Also, in support of our hypothesis, we found that immobilized aprotinin within fibrin gels demonstrated substantial blood vessel invasion.     

Histochemical study of alkali-burned rabbit anterior eye segment in which severe lesions were prevented by aprotinin treatment

Summary Activities of different enzymes (acid glycosidases, phosphatases, Na⁺–K⁺-dependent ATPase, proteases, dehydrogenases) and acid glycosaminoglycans were studied by histochemical methods in sections of rabbit anterior eye segments after experimental alkali burn and treatment with aprotinin, an inhibitor of plasmin and other serine proteinases. Solutions of sodium hydroxide (0.25–1.0M) were applied on corneas using 12-mm-diameter plastic tube for 15–60 s. After wiping with cotton and rinsing with tap water, aprotinin solutions were applied in saline (in experimental animals) and saline (in control animals) dropwise in 12-h intervals for a month. Within the first two weeks aprotinin was used at a concentration of 5000 IU/ml. During the subsequent two weeks the aprotinin concentration was reduced to 2500 IU/ml.Striking differences in enzyme activities and in the healing between treated and untreated eyes were found. Without aprotinin, ulcers developed in most corneas within 3 weeks and plasmin was regularly demonstrated in tears and in the aqueous. When aprotinin treatment was started within 24 h after the burn, the number of enzymatically active inflammatory cells was significantly lower, not only in the cornea itself but also in the whole anterior eye segment. With aprotinin treatment no ulcerations and no plasmin in tears and the aqueous were observed and the corneas healed within a month. The healing process started from the zone of enzymatically activated corneal cells in the unburned zone at the corneal periphery. In the regenerating epithelium and endothelium high activities of Na⁺–K⁺-dependent ATPase, -glutamyltransferase, lactate and succinate dehydrogenases appeared very soon. Keratocytes displayed high activities of all enzymes studied. The restoration of corneal transparency depended on concentration of alkali used and parallelled the regeneration of the stroma and normalization of corneal hydration. Our results demonstrate that aprotinin is a potent therapeutic agent in the treatment of experimentally induced corneal ulcers, presumably due to its inhibitory action on plasmin and other serine proteases present in the alkali-burned anterior eye segment.     

Vitamin A supplementation improves macrophage function and bacterial clearance during experimental salmonella infection

The effects of additional but nontoxic amounts of vitamin A on susceptibility to salmonella infection was studied by comparing rates of bacterial clearance and phagocytosis. Forty-eight male Lewis rats were divided into a treatment group receiving a total of 6000 units of vitamin A palmitate weekly for 5 weeks and a control group was given an equal volume of saline. After completion of the treatment regimen, one-half from each group were infected intraperitoneally with 10(5) Salmonella typhimurium; the other half received intraperitoneal injection of saline. At this time no differences in weight gain were noted and all animals were sacrificed within 2 weeks. At 72 hr after bacterial challenge, all saline-treated control animals displayed bacteremia. Cultures of liver and splenic homogenates were positive in 89 and 100% of infected control animals vs 0 and 44% for treated animals during the first week of infection. Kupffer cell, peritoneal, and splenic macrophages of the vitamin A-treated group had greater phagocytic activity than controls as assessed by the percentage of cells ingesting yeast particles and by the number of particles ingested (phagocytic index). These results suggest that vitamin A in moderate amounts may benefit the host's response to infection by enhancing phagocytic cell function.     

Effect of duodenal trypsin on pancreatic secretion in men

The effect of tryptic activity in duodenum on L-phenylalanine (100 mmol.1-1 intraduodenally) stimulated pancreatic secretion in 18 healthy volunteers has been evaluated. Intraduodenal infusion of trypsin (150 mg) during 1 h caused the reduction of alpha-amylase and lipase output by ca 30%. The infusion of aprotinin at the dose of 0.5.10(6) KIU during 30 min caused return of the alpha-amylase and lipase output to the pretryptic values. The infusion of trypsin in higher dose (300 mg) caused more pronounced decrease of amylase and lipase output (ca 45%). Our data indicate that active trypsin in duodenum is responsible for the inhibition of L-phenylalanine stimulated pancreatic enzyme secretion in man. These results corroborate the existence of feedback regulation of stimulated pancreatic secretion by intraduodenal trypsin in man.     

Adsorption on synthetic membranes and immunogenic properties of aprotinin cross-linked by glutaraldehyde]

A procedure for the intermolecular crosslinking of aprotinin (natural polypeptide, an inhibitor of serine proteases) by glutaraldehyde was proposed. This autoconjugation of aprotinin increased its immunogenicity and the efficiency of sorption on nitrocellulose and polyvinylidene difluoride membranes. The immunization of animals by the autoconjugated aprotinin induced the production of antibodies that reacted with both conjugated and monomeric aprotinin. The properties of the crosslinked aprotinin are promising for the enhancement of sensitivity through its use in EIA and immunoblotting membrane methods that employ aprotinin and antiaprotinin antibodies.     

The effect of a liquid elemental diet on cell proliferation in the colon of rats

Summary A liquid elemental diet (Vivonex) was given to rats for 6 days while control animals received a normal diet. At the end of the experiment each animal received one intraperitoneal injection of tritiated thvmidine at 8a.m. Animals from each group were killed hourly during the first 24h after the injection and the proliferative activity was studied by autoradiography of the mucosa of the colon using the labeled mitoses-wave method.The epithelial cell proliferation was significantly decreased in the colon of the Vivonex-fed animals.     

Absorption of Escherichia coli endotoxin (lipopolysaccharide) from the uteri of postpartum dairy cows

An experiment was conducted to test the hypothesis that Escherichia coli (E. coli ) endotoxin is readily absorbed from uteri of early postpartum cows and that the absorbed endotoxin provokes systemic relcase of prostaglandins. Eleven postpartum Holstein dairy cows (aged 3 to 7 yr) with normal puerperium were selected and divided into a treatment group (n=7), which received intrauterine infusions of E. coli endotoxin, and a control group (n=4), which received intrauterine infusions of 10 ml of saline on Days 5 and 20 post partum. Blood samples were collected once every 30 min for 6 h starting from the time of infusion. Harvested sera samples were analyzed for concentrations of stable metabolites of prostacyclin (PCM), prostaglandin F(2alpha) (PGFM), and thromboxane A(2) (TXB(2)). Plasma samples were qualitatively tested for the presence of endotoxin. Endotoxin was detected in the plasma samples of cows that received endotoxin on Day 5 post partum 4 h after the infusion. Endotoxin was not detected in any of the samples from control cows on Days 5 and 20 post partum or from treatment group cows on Day 20 post partum. Cows treated on Day 5 post partum showed increases in serum PGFM concentrations from 710 +/-64pg/ml to peak concentrations of 1223 +/- 47 pg/ml within 2 h, followed by a decline to baseline concentrations within 4 h. The amount of PGFM released in treated cows on Day 5 post partum was higher (P < 0.05) than in control cows on Day 5 or in treated and control cows on Day 20 post partum. Serum PCM concentrations increased from 156+/-24 pg/ml to peak concentrations of 1348+/-127 pg/ml within 1 h. The amount of PCM released in treated cows on Day 5 postpartum was higher (P< 0.05) than in control cows on Day 5 or in treated and control cows on Day 20 post partum. The TXB(2) concentrations increased from 315+/-38 pg/ml to peak concentrations of 5043 +/- 242 pg/ml within 1 h and fell to baseline concentrations within 5 h. The amount of TXB(2) concentrations released in treated cows on Day 5 post partum was significant (P < 0.05) compared with those of cows in the other groups. The results support the hypothesis that uteri of early postpartum cows are capable of absorbing endotoxin, and the absorbed endotoxin provokes changes in the serum concentrations of prostanoids.     

Local Delivery of Nimodipine by Prolonged-Release Microparticles—Feasibility,Effectiveness and Dose-Finding in Experimental Subarachnoid Hemorrhage

Background and Purpose

To investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH).

Methods

70 male Wistar rats were categorized into three groups: 1) sham operated animals (control), 2) animals with SAH only (control) and the 3) treatment group. SAH was induced using the double hemorrhage model. The treatment group received different concentrations (20%, 30% or 40%) of nimodipine microparticles. Angiographic vasospasm was assessed 5 days later using digital subtraction angiography (DSA). Histological analysis of frozen sections was performed using H&E-staining as well as Iba1 and MAP2 immunohistochemistry.

Results

DSA images were sufficient for assessment in 42 animals. Severe angiographic vasospasm was present in group 2 (SAH only), as compared to the sham operated group (p<0.001). Only animals within group 3 and the highest nimodipine microparticles concentration (40%) as well as group 1 (sham) demonstrated the largest intracranial artery diameters. Variation in vessel calibers, however, did not result in differences in Iba-1 or MAP2 expression, i.e. in histological findings for secondary brain injury.

Conclusions

Local delivery of high-dose nimodipine prolonged-release microparticles at high concentration resulted in significant reduction in angiographic vasospasm after experimental SAH and with no histological signs for matrix toxicity.     

Carbohydrate-containing derivatives of the trypsin-kallikrein inhibitor aprotinin from bovine organs. I. Modification with lactose, characterization and behaviour of the preparation in vivo

The trypsin-kallikrein inhibitor aprotinin was modified with lactose. The influence of reactant concentrations, temperature, reaction time and sodium borohydride on the carbohydrate residue content and the inhibiting activity of glycated aprotinin were studied. Glycation of aprotinin neither shifts the pH optimum of the inhibitor-trypsin association reaction nor does it alter the apparent dissociation constant Ki of the complex measured at pH optimum. Glycation by lactose stabilizes aprotinin against denaturation by increased temperature. The distribution of native and modified aprotinin in rat organs after endocardiac injection was studied. Fixation of glycated aprotinin increases 2.5- to 3-fold in liver and decreases 2-fold in kidneys during the observation time (5 min-2 h) compared to native aprotinin.     

Modification of the toxicity of Bothrops atrox poison by interventions in the coagulation and kallikrein system of prey

LD50-determinations with venom mixtures from different age groups of Bothrops atrox were carried out on differently pretreated mice. No differences were seen in the LD50 when comparing untreated mice with mice previously defibrinogenated with batroxobin. Inhibition of the coagulation-, kallikrein-kinin- and fibrinolytic system by pretreatment with batroxobin and aprotinin led to a significantly decreased toxicity of the venom mixtures of all age groups. The age-related difference in toxicity had practically disappeared. Furthermore, the number of mice of the latter group dying within one hour after the venom injection was strongly reduced as compared to untreated and only batroxobin-treated animals. Tests performed on rats showed that the rapidly occurring lethality following the venom injection as a consequence of circulatory disturbances (strong fall of arterial blood pressure, bradycardia, dyspnea), may be prevented almost completely by preincubation of the venom with aprotinin.     

Effect of glutathione on mitomycin C-induced micronuclei in bone marrow erythrocytes of Swiss albino mice

The antimutagenic potential of glutathione (GSH) on mitomycin C (MMC)-induced micronuclei was evaluated in Swiss albino mice using the in vivo bone marrow micronucleus test. Six groups of animals were maintained simultaneously. The first group received distilled water only, the second group of animals received 2 mg/kg MMC and the third group was administered 4 doses of GSH, i.e., 20, 40, 80 and 160 mg/kg. The fourth group of animals received GSH and MMC simultaneously. The fifth and sixth groups received a cumulative dose of GSH followed by MMC after 24 h. The fifth group of animals were killed 6 h after the administration of MMC, while the sixth group were killed 24 h after the administration of MMC. The results clearly show a statistically significant increase in micronuclei in MMC-treated animals and also in animals that received GSH followed by MMC. However, there was a decrease in micronuclei in animals that received GSH and MMC simultaneously. The results clearly indicate that GSH exhibits an antimutagenic property in the presence of MMC. It is also observed the treatment with GSH prior to MMC does have some protective effect.     

抑肽酶抑制体外循环中炎症反应的应用研究

目的:总结抑肽酶抑制体外循环心脏直视手术中炎性反应的研究和临床应用。方法:自2001年1月至11月,因心脏瓣膜病变而施行心脏瓣膜置换手术的患者随机分为研究组和对照组,术中应用抑肽酶的患者作为研究组。两组患者的体外循环、麻醉方法、预充液配制及手术方式间无差异。分别在体外循环前、中、后监测IL-6、IL-8和TNF-α变化。结果:两组患者CPB开始前的各炎性因子浓度间无显著性差异(P>0.05),而体外循环开始至结束后对照组患者的各炎性因子浓度均比研究组患者显著增加(P<0.05)。结论:抑肽酶能有效的抑制体外循环术中IL-6、IL-8和TNF-α的释放,减轻体外循环术后炎性反应的程度,这对促进患者术后恢复、减少术后并发症具有重要的意义。