Recombinant human granulocyte colony-stimulating factor and Pseudomonas burn wound sepsis

Multiple immune defects have been demonstrated following thermal injury, including defective granulocyte production and function. Recombinant human granulocyte colony-stimulating factor (rhGCSF) is a regulator of the myelopoietic system. The effect of rhGCSF administration on survival and on the myelopoietic system in a murine model of Pseudomonas burn wound sepsis was investigated. Male BDF1 mice that underwent a 15% total body surface area burn injury and burn wound seeding with 1 x 10(8) Pseudomonas aeruginosa organisms demonstrated an improved mean survival time with the subcutaneous administration of 100 ng of rhGCSF twice a day. Mice that underwent a similar thermal injury and burn wound seeding with 3 x 10(7) P aeruginosa organisms demonstrated an augmented myelopoietic response through the administration of rhGCSF, as represented by significantly increased white blood cell count, neutrophil count, splenic weight, femoral marrow cellularity, and femoral marrow granulocyte-macrophage colony-forming cell count. Myelopoietic augmentation through rhGCSF administration may serve to decrease the morbidity of septic events following thermal injury.     

The effects of ketamine and propofol on bacterial translocation in rats after burn injury

BACKGROUND: Bacterial translocation (BT) occurs after thermal injury and may result from an ischemic intestinal insult. The aim of the study was to investigate the effects of ketamine and propofol as anesthetic agents on BT in an animal model of burn injury. METHODS: Sixty male Wistar Albino rats were randomly assigned to six groups of 10 rats each. Anesthesia was induced and maintained with ketamine in groups 1, 2 and 3 and with propofol in groups 4, 5 and 6 during 6 h. Groups 2, 3, 5 and 6 received 30% total body surface area (TBSA) third-degree burns. Groups 1 and 4 had no burn injury. Then, they were allowed to recover from the anesthesia at the end of 6 h. Mean arterial pressure (MAP) was monitored continuously and maintained within 10% of baseline (before burn injury) levels in all animals. Animals in groups 3 and 6 had a laparotomy to obtain a tissue sample from the terminal ileum for determination of intestinal lipid peroxidation by-product malondialdehyde (MDA) before (baseline) and 6 and 24 h after burn injury (ABI). So these animals were not included in the BT studies. At postburn 24 h, animals in groups 1, 2 and 4, 5 were sacrified and samples were taken from the mesenteric lymph nodes (MLN), liver and spleen for bacteriologic cultures. RESULTS: The incidence of BT was found to be significantly higher in group 2 than in all the other groups. Bacterial translocation incidence of group 5 was not significantly different from that of groups 4 and 1. Group 5 was associated with a significantly reduced number of enteric organisms per gram of tissue compared to group 2. Baseline MDA contents of groups 3 and 6 were similar. Ileal MDA levels were increased in group 3, but there were no significant changes in group 6 at 6 and 24 h ABI compared to baseline. CONCLUSION: Our results suggest that propofol as an anesthetic agent may prevent BT by scavenging reactive oxygen species and inhibiting lipid peroxidation in an animal model of burn injury.     

烧伤创面脓毒症诊断的细菌学意义及临床分期

目的　探讨并重新评价烧伤创面脓毒症与组织细菌定量的关系 ,将其进行临床分期。　方法　对近 5年符合条件的 32例烧伤患者进行组织细菌检查和定量分析 ,结合临床表现对创面脓毒症进行分期。　结果　 (1) 32例患者的 12 3个组织标本中 ,均可见到细菌侵入 ,有 82个标本的每克痂下组织菌量≥ 1× 10 5,4 1个标本的每克痂下组织菌量 <1× 10 5。其中 18例患者 6 8个标本 ,每克痂下组织菌量全部≥ 1× 10 5;5例患者 2 0个标本 ,每克痂下组织菌量全部 <1× 10 5;其余 9例患者的标本中仅部分每克痂下组织菌量≥ 1× 10 5。 (2 )根据细菌学结果并结合临床表现 ,可将创面脓毒症分为Ⅰ～Ⅳ期。　结论　 (1)临床有中毒表现并获得细菌侵入活组织的证据时 ,创面脓毒症的诊断即可成立。 (2 )将创面脓毒症分为IV期 ,有助于规范临床诊断、指导临床治疗     

The effect of extensive excision of burn wound with invasive infection on hypermetabolism in burn patients with sepsis

Objective: To evaluate the effect of extensive excision of invasive burn wound infection on hypermetabolic response in burn patients with sepsis. Methods:Eight patients with major burn, complicated by invasive burn wound infection and sepsis were consecutively admitted to our hospital from September 1997 to October 1998. REEs were monitored by means of Cardiorespiratory Diagnostic System (Medical Graphics Corporation, USA) at patients bedside. Plasma concentration of IL-6、IL-8、TNF-α and LPS were assayed before and after surgical intervention and at the time when the patients' vital signs became stable. Correlation analysis between REEs and IL-6、IL-8、TNF-α、LPS was respectively made. Results: A total of 8 patients were treated and all of them survived. Values of REE before surgical intervention were significantly higher than those after surgical intervention(P＜0.01), and when patients vital signs became stable the values were significantly lower compared with that after surgical intervention(P＜0.01). The plasma concentrations of IL-6、 IL-8、TNF-α and LPS after excision of invasive burn wound infection were significantly lower than those before surgical intervention (P＜0.05). The lowest levels of these inflammatory mediators were observed when the conditions of patients became stable, and the values were significantly lower compared with those before surgical intervention (P＜0. 001). There was a significant positive correlation between REE level and respective values of plasma IL-6、 IL-8、 TNF-α、 LPS(P ＜0.01). Conclusions: It is deemed that the extensive excision of invasively infected burn wound in patients with major burn should be performed as early as possible to reduce an increased release of inflammatory mediators, and to control the hypermetabolic response during sepsis.     

Clinical characteristics and treatment of burn wound sepsis in extensive burn patients: successful experience with eight cases

Eight burn wound sepsis patients, in which 6 cases were diagnosed as MODS and two as septic shock, were treated consecutively in our hospital from September 1997 to October 1998. The plasma concentration of IL-6, IL-8, TNFα and LPS were assayed before and after surgical intervention, as well as when the patients' vital signs became stable. The results showed: ①The patients' conditions abruptly deteriorated when the burn wound sepsis emerged;②The major cause related to burn wound sepsis was extensive burn injuries, with large areas of deep burn remaining open; ③Although wound swabs taken on admission revealed the presence of colonization by many pathogenic bacteria, Pseudomonas aeruginosa was one of the most frequent bacteria isolated from the subeschar tissue; ④The plasma concentrations of IL-6, IL-8, TNF and LPS before surgical intervention were significantly higher than that after surgical intervention (P＜0.05) ;⑤The lowest level of the inflammatory mediators was observed when the patients' conditions became stable, as compared with before surgical intervention (P＜0. 001).These findings suggest that the clinical characteristics of burn wound sepsis are abrupt deterioration of the general condition and prominent septic symptoms, often complicated by MODS. The main cause of burn wound sepsis is the presence of a large area of open deep burn wounds, which should be excised and covered early. LPS and pro-inflammatory mediators play an important role in the pathogenesis of burn wound sepsis. Although success in treating these patients is the result of appropriate application of multiple treatments, early, aggressive and thorough surgical excision of invasive burn infectious tissue and closure of wound play a crucial role in the successful treatment of patients complicated by burn wound sepsis. Other treatments are adjuvant but also important.     

Therapy with anti-flagellin A monoclonal antibody limits Pseudomonas aeruginosa invasiveness in a mouse burn wound sepsis model

Background

The aim of this study was to evaluate the effect of an anti-flagellin sub-type monoclonal antibody (anti-fla-a) on Pseudomonas aeruginosa infection in a mouse burn model and to assay bacterial dissemination and invasiveness.

Methods

After immediate post-burn infection with P. aeruginosa, mortality and morbidity (daily weight changes) were monitored in mice treated with anti-fla-a as compared to untreated mice. Bacterial dissemination and invasiveness were monitored by bacterial counts at the burn site and spleen. Three different timing regimens for anti-fla-a treatment were studied: (a) prophylaxis (pre-infection), (b) therapeutic (post-infection), and (c) combined mode.

Results

Combined regimen of anti-fla-a markedly improved survival of mice infected with P. aeruginosa from 6% to 96% (p < 0.0001), similar to treatment with Imipenem. Furthermore, a significant improvement in survival was obtained when anti-fla-a was given prior to (75% survival) or post-infection (50% survival). It reduced bacterial load in the spleen (p = 0.01), preventing bacterial sepsis.

Conclusion

Anti-fla-a is effective in reducing mortality and morbidity in murine P. aeruginosa-infected burn model.     

大面积侵袭感染组织切除对烧伤创面脓毒症患者静息能量消耗的影响

目的观察大面积侵袭感染组织切除对烧伤创面脓毒症患者高代谢的影响。方法对连续救治的8例烧伤创面脓毒症患者,分别于大面积侵袭感染组织切除前,手术后和病情稳定时,对静息能量消耗(restingenergyexpenditure,REE)白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子α(TNFα)、内毒素(LPS)进行监测。结果侵袭感染组织切除后REE水平[(307.7±31.3)kJ·h     

The effect of granulocyte macrophage-colony stimulating factor on bacterial translocation after administration of 5-fluorouracil in rats

BACKGROUND: After surgical resection for colorectal carcinoma there is a high recurrence rate and, therefore, adjuvant chemotherapy may be useful in some patients. 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent in the management of patients with colorectal cancer. However, gastrointestinal injury induced by chemotherapeutic agents may result in bacterial translocation from the gut into the systemic circulation. Granulocyte macrophage-colony stimulating factor (GM-CSF) may be used to prevent this side effect by means of macrophage activity stimulation. MATERIALS AND METHODS: A total of 45 rats were divided into three groups. Control group received intraperitoneal saline solution, 5-FU and GM-CSF groups received 50 mg/kg/day 5-FU intravenous infusion and GM-CSF group also received 200 ng/day GM-CSF subcutaneously for 6 days. Intestinal tissue was also sampled for pathological examination at day 7. Plasma levels of tumor necrosis factor-alpha and interleukin-6 were determined, bacterial translocation was quantified by lymph node, liver and spleen culture, and plasma endotoxin content was measured. RESULTS: White blood cell counts of the 5-FU rats were significantly lower than in the control and GM-CSF groups (P < 0.01). The plasma endotoxin, tumor necrosis factor-alpha and interleukin-6 levels in the 5-FU and GM-CSF groups were significantly increased at day 7 compared with the control groups (P < 0.01), but these levels were significantly lower in the GM-CSF group compared to the 5-FU group (P < 0.01). 5-FU intervention caused significant increase in the frequencies of bacterial translocation at liver, spleen, mesenteric lymph node, and portal blood. Compared with 5-FU group, GM-CSF decreased the bacterial translocation (P < 0.01). CONCLUSIONS: This study observed that the administration of 5-FU resulted in bacterial translocation. Activation of inflammatory response with GM-CSF is highly effective in prevention of bacterial translocation in 5-FU interventions.     

Causes of surgical sepsis including bacterial translocation

Sepsis is defined as the systemic inflammatory response syndrome (SIRS) associated with suspected or confirmed infection. As such, it is implicit that two components are necessary in the causation of surgical sepsis; namely a source of infection as well as a SIRS response by the patient. This article reviews some of the better known causes and predisposing factors for sepsis, including that of the passage of viable bacteria or its components across the gut barrier in a process known as bacterial translocation (BT). A particular emphasis is paid to the development of sepsis in surgical patients. The common infections encountered in surgical patients are also discussed together with the specific definitions used in relation to surgical site infections.     

The effect of sepsis on wound healing.

BACKGROUND: Normal wound healing is a regulated sequence of events that successfully restore tissue integrity. Previous studies have suggested that wound healing is impaired in a septic host. The current study examines the effect of sepsis on the inflammatory and proliferative phases of wound healing at a remote site of secondary injury. METHODS: Polyvinyl alcohol sponges, either inoculated with a standard dose of Pseudomonas aeruginosa (experimental) or soaked in normal saline (control), were placed subcutaneously in the anterior abdominal region of male B6D2F1 mice. Immediately following sponge placement, full thickness excisional dermal wounds were created on the dorsum. Wound healing was examined at days 3, 5, and 7 postinjury. The infiltration of neutrophils and macrophages into wounds was quantified, and the reepithelialization rate and collagen content were measured. RESULTS: Peripheral neutrophil counts were significantly elevated in infected mice, yet neutrophil content of the remote wound of infected animals was significantly reduced (5% of control, P < 0.05). Wounds of infected mice also showed a 30% reduction in the macrophage content. Wounds of infected animals exhibited delayed reepithelialization (76 +/- 3 vs 97 +/- 3% at day 5, P < 0.05) and collagen synthesis (55.3 +/- 9.5 vs 105 +/- 13.0 microg/wound, P < 0.05). CONCLUSION: Systemic infection alters both the inflammatory and the proliferative processes at remote sites of injury. Multiple factors seem likely to contribute to the increased incidence of wound complications in septic patients.     

重组人粒细胞巨噬细胞集落刺激因子凝胶剂对深Ⅱ度烧伤创面溶痂及愈合影响的临床研究

目的通过临床对比研究,探讨重组人粒细胞巨噬细胞集落刺激因子(recombinant human granulocyte-macrophage colony-stimulating factor,rhGMCSF)凝胶剂对深Ⅱ度烧伤创面溶痂及愈合的作用及其机制。方法以2008年12月-2010年12月收治的符合选择标准的58例深Ⅱ度烧伤患者作为试验对象。男36例,女22例;年龄12～67岁,平均32.4岁。热液烫伤38例,火焰烧伤20例。受伤至治疗时间为1～3d,平均2.1d。采用随机双盲、自身对照方法,分为给予rhGMCSF凝胶剂治疗组(试验组)及不含rhGMCSF的凝胶剂基质治疗组(对照组)。两组用药面积比较差异无统计学意义(P>0.05),具有可比性。用药后观察创面情况,于2、6、10、14、18d计算创面溶痂率,记录完全溶痂时间及创面愈合时间。结果与对照组相比,试验组用药4d后黄白色坏死组织或痂皮逐渐变软;6d后坏死组织易浮动而脱落或痂皮边缘翘起,基底红白相间,深层肉芽组织增长迅速;8d时痂皮基本溶解。用药2d后试验组创面溶痂率即高于对照组,除用药后18d,其余各时间点两组创面溶痂率比较差异均有统计学意义(P<0.05)。试验组完全溶痂时间为(7.71±2.76)d,较对照组(14.71±3.63)d明显缩短(t=13.726,P=0.000);创面愈合时间为(18.41±2.47)d,亦较对照组(23.58±3.35)d明显缩短(t=15.763,P=0.000)。结论 rhGMCSF凝胶剂与单纯凝胶剂基质相比能促进深Ⅱ度烧伤创面坏死组织脱落,加快创面愈合。     

Effect of granulocyte colony-stimulating factor (G-CSF) on chemotherapy-induced oral mucositis

In this study, the ability of granulocyte colony-stimulating factor (G-CSF) to treat or prevent chemotherapy-induced oral mucositis in patients with advanced breast cancer was evaluated. A total of 14 patients who received intra-arterial (i.a.) adriamycin (ADM) preoperatively were divided into two groups according to whether or not G-CSF was given. Thus, group A (n=7) was given G-CSF and group B (n=7) was not. G-CSF therapy reduced both the incidence and duration of ADM-induced oral mucositis, and a positive correlation was also seen between the incidence of mucositis and ADM-induced leukopenia (<2,000/mm³). Group A was further divided into two subgroups according to whether G-CSF was given after or before the leukopenia had dropped below 2,000/mm³: group A-1 (n=3) and group A-2 (n=4), respectively. ADM-induced mucositis was observed in two of the three patients in group A-1, but in none of the four patients in group A-2. These results strongly support the idea that G-CSF can effectively treat and prevent ADM-induced oral mucositis.     

Cytotoxicity of topical antimicrobial agents used in burn wounds in Australasia

Background: Burn sepsis is a leading cause of mortality and morbidity in patients with major burns. The use of topical antimicrobial agents has helped improve the survival of these patients. Silvazine (Sigma Pharmaceuticals, Melbourne, Australia) (1% silver sulphadiazine and 0.2% chlorhexidine digluconate) is used exclusively in Australasia, and there is no published study on its cytotoxicity. This study compared the relative cytotoxicity of Silvazine with 1% silver sulphadiazine (Flamazine (Smith & Nephew Healthcare, Hull, UK)) and a silver‐based dressing (Acticoat (Smith & Nephew Healthcare, Hull, UK)). Methods: Dressings were applied to the centre of culture plates that were then seeded with keratinocytes at an estimated 25% confluence. The plates were incubated for 72 h and culture medium and dressings then removed. Toluidine blue was added to stain the remaining keratinocytes. Following removal of the dye, the plates were photographed under standard conditions and these digital images were analysed using image analysis software. Data was analysed using Student’s t‐test. Results: In the present study, Silvazine is the most cytotoxic agent. Seventy‐two hour exposure to Silvazine in the present study results in almost no keratinocyte survival at all and a highly statistically significant reduction in cell survival relative to control, Acticoat and Flamazine (P < 0.001, P < 0.01, P < 0.01, respectively). Flamazine is associated with a statistically significant reduction in cell numbers relative to control (P < 0.05), but is much less cytotoxic than Silvazine (P < 0.005). Conclusion: In this in‐vitro study comparing Acticoat, Silvazine and Flamazine, Silvazine shows an increased cytotoxic effect, relative to control, Flamazine and Acticoat. An in‐vivo study is required to determine whether this effect is carried into the clinical setting.     

粒细胞集落刺激因子免疫调节胚胎植入的研究进展

免疫因素介入的反复种植失败和复发性流产是导致不孕不育的常见原因之一。近年来,应用粒细胞集落刺激因子(Granulocyte-Colony Stimulating Factor,G-CSF)改善子宫内膜容受性,提高临床胚胎着床率、降低复发性流产逐渐成为相关研究热点。本文从其作用机制和临床应用两个方面对G-CSF在辅助生殖医学中的最新研究进展,进行了综述。     

Influence of insulin therapy on burn wound healing in rats

BACKGROUND: Insulin is proposed as a therapy for suppressing muscle wasting after burn trauma although the long-term effects of this therapy on wound healing are not yet known. The present study was designed to investigate the effect of systemically administered insulin therapy on burn wound healing. MATERIALS AND METHODS: Young rats weighing 80-150 g were subjected to 15-20% total body surface area burn injury on their shaved dorsum. The insulin dosage was increased over the first 3 days in each rat from 0.25 U (Day 1), 0.5 U (Day 2), and 1.0 U (Day 3) per 100 g body wt. The rats were euthanized at the fourth or fifteenth day postinjury. Skin sections were analyzed by histochemistry and quantitative polarization microscopy. RESULTS: Histology showed a decreased number of inflammatory cells and increased vasodilation in the insulin-treated animals at Day 4 relative to untreated rats; at Day 15 there was increased reepithelialization. Quantitative analysis using polarization microscopy and picrosirius red staining showed an increased collagen deposition in wounds by Day 4 in insulin-treated rats relative to untreated burn controls. CONCLUSION: These results indicate that insulin induces accelerated wound healing associated with diminished inflammation and increased collagen deposition.     

胰岛素联合生长因子及湿性敷料处理难愈性烧伤残余创面的疗效研究

目的研究胰岛素联合生长因子及湿性敷料处理难愈性小面积深度烧伤残余创面的临床疗效。方法将40例深度烧伤后形成小面积难愈性残余创面168处的患者进行自身对照,在早期少量多次清创的基础上,采用胰岛素联合生长因子贝复剂湿敷后给予湿性敷料包扎(改进法,100处),与仅外喷生长因子后给予碘伏敷料湿敷包扎的常规法(68处)进行效果比较。结果两法换药疼痛评分、创面平均愈合时间、创面愈合率、不同时期创面分泌物细菌培养阳性率比较,差异有统计学意义(均P<0.01)。结论采用胰岛素联合生长因子及湿性敷料处理难愈性小面积深度烧伤残余创面,能提高创面愈合速度及愈合质量,减少患者痛苦,缩短住院时间。     

An injectable metal nanoparticle containing cellulose derivative‐based hydrogels: Evaluation of antibacterial and in vitro‐vivo wound healing activity in children with burn injuries

The preparation of hydrogels for wound healing properties with high antibacterial activities and good biosafety concurrently can be relatively challenging. For addressing these issues, we report on the synthesis and characterisation of a nanocomposite hydrogel dressing by introducing the silver nanoparticles in hydroxypropyl methylcellulose‐hydroxyapatite scaffold hydrogel (HMC‐HA/AgNPs). The different concentrations of AgNPs in HMC‐HA/AgNPs hydrogels were confirmed by swelling ratio, degradation, and gelatin time. The synthesised HMC‐HA/AgNPs hydrogels were further characterised using the UV‐visible, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectrum, and X‐ray diffraction. The results showed that the novel HMC‐HA/AgNPs hydrogel exhibited a porous 3D network and high mechanical properties because of the inter‐molecular and intra‐molecular interactions. The AgNPs give the HMC‐HA hydrogels excellent antibacterial activities against both Staphylococcus aureus and Escherichia coli, without any chemical reductant and cross‐linking agent required endows the hydrogel high biocompatibility. More importantly, HMC‐HA/AgNPs effectively repaired wound defects in mice models, and wound healing reached 94.5 ± 1.4% within 16 days. The HMC‐HA hydrogel with AgNPs showed excellent antimicrobial activity and burn wound healing. Therefore, these HMC‐HA/AgNPs hydrogels have great potential as an injectable hydrogel for wound healing activity in children with burn injuries.     

脱细胞异体真皮与自体微粒皮复合移植治疗深度烧伤愈合后皮肤质量观察

目的：为大面积深度烧伤创面修复选择良好的覆盖材料,以解决自体中厚皮源不足的难题;提高创面愈合质量。方法：对16例大面积烧伤患者切削痂后分二组植皮,实验组：采用脱细胞异体真皮基质和自体微粒皮复合移植（简称复合皮移植）,对照组：单纯用微粒皮移植,并用温哥华瘢痕评量表定期随访观察创面近、远期效果。结果：术后1个月,实验组与对照组创面愈合的外观、质地、耐磨性、关节的功能及温哥华评分无明显差异。术后6个月,12个月,实验组创面愈合后的外观、质地、耐磨性、关节功能及温哥华瘢痕评分明显优于对照组。结论：对大面积深度烧伤患者行复合皮移植,可减轻瘢痕增生,改善创面外观及关节功能,可达到中厚皮移植的效果。     

Ovariectomy fails to augment bone resorption and marrow B lymphopoiesis in granulocyte colony-stimulating factor transgenic mice

The mechanism of pathological bone loss induced by estrogen deficiency has not been fully elucidated. It has been shown in recent animal studies that increased B lymphopoiesis induced by estrogen deficiency is involved in the mechanism of stimulated bone resorption. Mice transgenic for granulocyte colony-stimulating factor (G-CSF) (G-Tg) exhibit generalized osteopenia with an increase in osteoclast number and enhancement of bone resorption, which coexists with enhanced hematopoiesis. When ovariectomy was performed on G-Tg, it did not further reduce bone mass as revealed by radiography, dual-energy X-ray absorptiometry, and peripheral quantitative computed tomography. Ovariectomy increased the amount of colony-forming units of interleukin 7 (CFU-IL-7) by threefold in the marrow of normal mice in association with an increase in the number of B220-positive cells expressing the receptor activator of nuclear factor-B ligand (RANKL). In contrast, the number of B220-positive cells expressing RANKL and CFU-IL-7 remarkably decreased in the marrow of G-Tg. Ovariectomy induced neither CFU-IL-7 nor B220-positive cells expressing RANKL in the marrow of G-Tg. Strong inhibition of B lymphopoiesis by G-CSF resulted in depletion of B cells expressing RANKL from the marrow, which may lead to resistance to bone loss due to ovariectomy. This observation suggests that B lymphopoiesis plays a possible role in bone loss in a condition of acute estrogen deficiency.     

Effect of platelet-activating factor antagonists (BN-52021, WEB-2170, and BB-882) on bacterial translocation in acute pancreatitis

Bacterial translocation is an important source of pancreas infection in acute pancreatitis. The effect of platelet-activating factor (PAF) in the pathogenesis of acute pancreatitis has been proved in various studies. The aim of this study was to determine whether potent PAF antagonists influence bacterial translocation in acute pancreatitis. Acute pancreatitis was induced in 62 Wistar rats by injection of 2.5% sodium taurocholate into the biliopancreatic duct. The rats treated with PAF factor antagonists received intravenous injection of WEB-2170 (10 mg/kg), lexipafant (5 mg/kg), and BN-52021 (5 mg/kg) 30 minutes before induction of acute pancreatitis. Six hours after induction of acute pancreatitis, bacteriologic cultures and histologic scoring of tissues were performed. There was a statistically significant reduction in bacterial translocation to the mesenteric lymph nodes and liver but not to the pancreas of the rats treated with PAF antagonists. No significant increase in the intestinal bacterial population of any group was found. There were no statistical differences between the pancreatic histologic scores of the groups. PAF antagonists reduced bacterial translocation to distant sites other than the pancreas, preventing the bacterial dissemination that occurs in the early phase of acute pancreatitis and may have beneficial effects on the evolution of this disease.